WorldWideScience

Sample records for beta interferon gamma

  1. Interferon Gamma-1b Injection

    Science.gov (United States)

    Interferon gamma-1b injection is used to reduce the frequency and severity of serious infections in people with chronic ... severe, malignant osteopetrosis (an inherited bone disease). Interferon gamma-1b is in a class of medications called ...

  2. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.

    NARCIS (Netherlands)

    Rudick, R.A.; Stuart, W.H.; Calabresi, P.A.; Confavreux, C.; Galetta, S.L.; Radue, E.W.; Lublin, F.D.; Weinstock-Guttman, B.; Wynn, D.R.; Lynn, F.; Panzara, M.A.; Sandrock, A.W.

    2006-01-01

    BACKGROUND: Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an alpha4 integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies.

  3. Evaluation of transformation growth factor beta1, interleukin-10, and interferon-gamma in male symptomatic and asymptomatic dogs naturally infected by Leishmania (Leishmania) chagasi.

    Science.gov (United States)

    Corrêa, Ana Paula Ferreira Lopes; Dossi, Ana Cláudia Silva; de Oliveira Vasconcelos, Rosemeri; Munari, Danísio Prado; de Lima, Valéria Marçal Felix

    2007-02-28

    The aims of this study were to evaluate the immunomodulatory role of TGF-beta1, IL-10, and INF-gamma in spleen and liver extracts and supernatant cultures of white spleen cells from male symptomatic and asymptomatic dogs, naturally infected by Leishmania (Leishmania) chagasi. Thirty dogs from Araçatuba, São Paulo, Brazil, an endemic leishmaniosis area, were selected by positive ELISA serological reaction for Leishmania sp. and divided into two groups: asymptomatic (n=15) and symptomatic (n=15) consisting of animals with at least three characteristic signs (fever, dermatitis, lymphoadenopathy, onychogryphosis, weight loss, cachexia, locomotion problems, conjunctivitis, epistaxis, hepatosplenomegaly, edema, and apathy). After euthanasia, spleen and liver fragments were collected for ex vivo quantification of TGF-beta1, IL-10, and INF-gamma. Naturally active in vitro produced TGF-beta1 was also evaluated in spleen cell culture supernatant. Spleen and liver extract of asymptomatic dogs had higher mean TGF-beta1 levels than symptomatic dogs. High concentrations of IL-10 were found in spleen, and mainly in liver extract of both groups. Higher INF-gamma concentrations were found in spleen extracts of symptomatic dogs, and in liver extracts of asymptomatic dogs. Extract of this cytokine was lower in spleen extract. Although INF-gamma is being produced in canine infection, mean levels of TGF-beta1 and IL-10 from spleen and liver extracts were quantitatively much higher; suggesting that immune response in both asymptomatic and symptomatic dogs was predominantly type Th2.

  4. Beta and Gamma Gradients

    DEFF Research Database (Denmark)

    Løvborg, Leif; Gaffney, C. F.; Clark, P. A.

    1985-01-01

    Experimental and/or theoretical estimates are presented concerning, (i) attenuation within the sample of beta and gamma radiation from the soil, (ii) the gamma dose within the sample due to its own radioactivity, and (iii) the soil gamma dose in the proximity of boundaries between regions...... of differing radioactivity. It is confirmed that removal of the outer 2 mm of sample is adequate to remove influence from soil beta dose and estimates are made of the error introduced by non-removal. Other evaluations include variation of the soil gamma dose near the ground surface and it appears...... that the present practice of avoiding samples above a depth of 0.3 m may be over-cautious...

  5. Simultaneous beta and gamma spectroscopy

    Science.gov (United States)

    Farsoni, Abdollah T.; Hamby, David M.

    2010-03-23

    A phoswich radiation detector for simultaneous spectroscopy of beta rays and gamma rays includes three scintillators with different decay time characteristics. Two of the three scintillators are used for beta detection and the third scintillator is used for gamma detection. A pulse induced by an interaction of radiation with the detector is digitally analyzed to classify the type of event as beta, gamma, or unknown. A pulse is classified as a beta event if the pulse originated from just the first scintillator alone or from just the first and the second scintillator. A pulse from just the third scintillator is recorded as gamma event. Other pulses are rejected as unknown events.

  6. Gamma-interferon alters globin gene expression in neonatal and adult erythroid cells

    International Nuclear Information System (INIS)

    Miller, B.A.; Perrine, S.P.; Antognetti, G.; Perlmutter, D.H.; Emerson, S.G.; Sieff, C.; Faller, D.V.

    1987-01-01

    The effect of gamma-interferon on fetal hemoglobin synthesis by purified cord blood, fetal liver, and adult bone marrow erythroid progenitors was studied with a radioligand assay to measure hemoglobin production by BFU-E-derived erythroblasts. Coculture with recombinant gamma-interferon resulted in a significant and dose-dependent decrease in fetal hemoglobin production by neonatal and adult, but not fetal, BFU-E-derived erythroblasts. Accumulation of fetal hemoglobin by cord blood BFU-E-derived erythroblasts decreased up to 38.1% of control cultures (erythropoietin only). Synthesis of both G gamma/A gamma globin was decreased, since the G gamma/A gamma ratio was unchanged. Picograms fetal hemoglobin per cell was decreased by gamma-interferon addition, but picograms total hemoglobin was unchanged, demonstrating that a reciprocal increase in beta-globin production occurred in cultures treated with gamma-interferon. No toxic effect of gamma-interferon on colony growth was noted. The addition of gamma-interferon to cultures resulted in a decrease in the percentage of HbF produced by adult BFU-E-derived cells to 45.6% of control. Fetal hemoglobin production by cord blood, fetal liver, and adult bone marrow erythroid progenitors, was not significantly affected by the addition of recombinant GM-CSF, recombinant interleukin 1 (IL-1), recombinant IL-2, or recombinant alpha-interferon. Although fetal progenitor cells appear unable to alter their fetal hemoglobin program in response to any of the growth factors added here, the interaction of neonatal and adult erythroid progenitors with gamma-interferon results in an altered expression of globin genes

  7. Stability of human interferon-beta 1: oligomeric human interferon-beta 1 is inactive but is reactivated by monomerization.

    Science.gov (United States)

    Utsumi, J; Yamazaki, S; Kawaguchi, K; Kimura, S; Shimizu, H

    1989-10-05

    Human interferon-beta 1 is extremely stable is a low ionic strength solution of pH 2 such as 10 mM HCl at 37 degrees C. However, the presence of 0.15 M NaCl led to a remarkable loss of antiviral activity. The molecular-sieve high-performance liquid chromatography revealed that, whereas completely active human interferon-beta 1 eluted as a 25 kDa species (monomeric form), the inactivated preparation eluted primarily as a 90 kDa species (oligomeric form). The specific activity (units per mg protein) of the oligomeric form was approx. 10% of that of the monomeric form. This observation shows that oligomeric human interferon-beta 1 is apparently in an inactive form. When the oligomeric eluate was resolved by polyacrylamide gel containing sodium dodecyl sulphate (SDS), it appeared to be monomeric under non-reducing conditions. Monomerization of the oligomeric human interferon-beta 1 by treatment with 1% SDS, fully regenerated its antiviral activity. These results suggest that the inactivation of the human interferon-beta 1 preparation was caused by its oligomerization via hydrophobic interactions without the formation of intermolecular disulphide bonds. These oligomers can be dissociated by SDS to restore biological activity.

  8. Effects of interferon-gamma and tumor necrosis factor-alpha on macrophage enzyme levels

    Science.gov (United States)

    Pierangeli, Silvia S.; Sonnenfeld, Gerald

    1989-01-01

    Murine peritoneal macrophages were treated with interferon-gamma (IFN-gamma) or tumor necrosis factor-alpha (TNF). Measurements of changes in acid phosphatase and beta-glucuronidase levels were made as an indication of activation by cytokine treatment. IFN-gamma or TNF-gamma treatment resulted in a significant increase in the activities of both enzymes measured in the cell lysates. This increase was observable after 6 h of incubation, but reached its maximum level after 24 h of incubation. The effect of the treatment of the cell with both cytokines together was additive. No synergistic effect of addition of both cytokines on the enzyme levels was observed.

  9. Differential expression of interferon-gamma and interferon-gamma-inducing cytokines in Thai patients with scrub typhus or leptospirosis

    NARCIS (Netherlands)

    Chierakul, Wirongrong; de Fost, Maaike; Suputtamongkol, Yupin; Limpaiboon, Roongreung; Dondorp, Arjen; White, Nicholas J.; van der Poll, Tom

    2004-01-01

    Interferon (IFN)-gamma plays an important role in the induction of a type 1 immune response against intracellular pathogens. We compared the plasma levels of IFN-gamma and IFN-gamma-inducing cytokines in adult Thai patients with scrub typhus, caused by the obligate intracellular bacterium Orientia

  10. A {beta} - {gamma} coincidence; Metodo de coincidencias {beta} - {gamma}

    Energy Technology Data Exchange (ETDEWEB)

    Agullo, F

    1960-07-01

    A {beta} - {gamma} coincidence method for absolute counting is given. The fundamental principles are revised and the experimental part is detailed. The results from {sup 1}98 Au irradiated in the JEN 1 Swimming pool reactor are given. The maximal accuracy is 1 per cent. (Author) 11 refs.

  11. Atorvastatin prevents age-related and amyloid-beta-induced microglial activation by blocking interferon-gamma release from natural killer cells in the brain

    LENUS (Irish Health Repository)

    Lyons, Anthony

    2011-03-31

    Abstract Background Microglial function is modulated by several factors reflecting the numerous receptors expressed on the cell surface, however endogenous factors which contribute to the age-related increase in microglial activation remain largely unknown. One possible factor which may contribute is interferon-γ (IFNγ). IFNγ has been shown to increase in the aged brain and potently activates microglia, although its endogenous cell source in the brain remains unidentified. Methods Male Wistar rats were used to assess the effect of age and amyloid-β (Aβ) on NK cell infiltration into the brain. The effect of the anti-inflammatory compound, atorvastatin was also assessed under these conditions. We measured cytokine and chemokine (IFNγ, IL-2, monocyte chemoattractant protein-1 (MCP-1) and IFNγ-induced protein 10 kDa (IP-10)), expression in the brain by appropriate methods. We also looked at NK cell markers, CD161, NKp30 and NKp46 using flow cytometry and western blot. Results Natural killer (NK) cells are a major source of IFNγ in the periphery and here we report the presence of CD161+ NKp30+ cells and expression of CD161 and NKp46 in the brain of aged and Aβ-treated rats. Furthermore, we demonstrate that isolated CD161+ cells respond to interleukin-2 (IL-2) by releasing IFNγ. Atorvastatin, the HMG-CoA reductase inhibitor, attenuates the increase in CD161 and NKp46 observed in hippocampus of aged and Aβ-treated rats. This was paralleled by a decrease in IFNγ, markers of microglial activation and the chemokines, MCP-1 and IP-10 which are chemotactic for NK cells. Conclusions We propose that NK cells contribute to the age-related and Aβ-induced neuroinflammatory changes and demonstrate that these changes can be modulated by atorvastatin treatment.

  12. Acetaminophen modulates the transcriptional response to recombinant interferon-beta.

    Directory of Open Access Journals (Sweden)

    Aaron Farnsworth

    Full Text Available BACKGROUND: Recombinant interferon treatment can result in several common side effects including fever and injection-site pain. Patients are often advised to use acetaminophen or other over-the-counter pain medications as needed. Little is known regarding the transcriptional changes induced by such co-administration. METHODOLOGY/PRINCIPAL FINDINGS: We tested whether the administration of acetaminophen causes a change in the response normally induced by interferon-beta treatment. CD-1 mice were administered acetaminophen (APAP, interferon-beta (IFN-beta or a combination of IFN-beta+APAP and liver and serum samples were collected for analysis. Differential gene expression was determined using an Agilent 22 k whole mouse genome microarray. Data were analyzed by several methods including Gene Ontology term clustering and Gene Set Enrichment Analysis. We observed a significant change in the transcription profile of hepatic cells when APAP was co-administered with IFN-beta. These transcriptional changes included a marked up-regulation of genes involved in signal transduction and cell differentiation and down-regulation of genes involved in cellular metabolism, trafficking and the IkappaBK/NF-kappaB cascade. Additionally, we observed a large decrease in the expression of several IFN-induced genes including Ifit-3, Isg-15, Oasl1, Zbp1 and predicted gene EG634650 at both early and late time points. CONCLUSIONS/SIGNIFICANCE: A significant change in the transcriptional response was observed following co-administration of IFN-beta+APAP relative to IFN-beta treatment alone. These results suggest that administration of acetaminophen has the potential to modify the efficacy of IFN-beta treatment.

  13. Interferon gamma, interferon-gamma-induced-protein 10, and tuberculin responses of children at high risk of tuberculosis infection

    DEFF Research Database (Denmark)

    Petrucci, Roberta; Abu Amer, Nabil; Gurgel, Ricardo Queiroz

    2008-01-01

    BACKGROUND: Children in contact with adults with pulmonary tuberculosis (TB) are at risk for infection and disease progression, and chemoprophylaxis may reduce this risk. The identification of infection is based on the tuberculin skin test (TST) and interferon-gamma (INF-gamma) release assays. Ot...

  14. Interferon gamma, interferon-gamma-induced-protein 10, and tuberculin responses of children at high risk of tuberculosis infection

    DEFF Research Database (Denmark)

    Petrucci, Roberta; Abu Amer, Nabil; Gurgel, Ricardo Queiroz

    2008-01-01

    BACKGROUND: Children in contact with adults with pulmonary tuberculosis (TB) are at risk for infection and disease progression, and chemoprophylaxis may reduce this risk. The identification of infection is based on the tuberculin skin test (TST) and interferon-gamma (INF-gamma) release assays...

  15. Interferon gamma peptidomimetic targeted to interstitial myofibroblasts attenuates renal fibrosis after unilateral ureteral obstruction in mice

    NARCIS (Netherlands)

    Poosti, Fariba; Bansal, Ruchi; Yazdani, Saleh; Prakash, Jai; Beljaars, Leonie; van den Born, Jacob; de Borst, Martin H.; van Goor, Harry; Hillebrands, Jan-Luuk; Poelstra, Klaas

    2016-01-01

    Renal fibrosis cannot be adequately treated since anti-fibrotic treatment is lacking. Interferon-gamma is a pro-inflammatory cytokine with anti-fibrotic properties. Clinical use of interferon-gamma is hampered due to inflammation-mediated systemic side effects. We used an interferon-gamma

  16. Rhabdomyolysis following interferon-beta treatment in a patient with multiple sclerosis

    DEFF Research Database (Denmark)

    Dalbjerg, Sara Maria; Tsakiri, Anna; Fredriksen, Jette Lautrup

    2016-01-01

    Background Multiple sclerosis is an inflammatory disease of the central nervous system for which there is currently no cure. Interferon-beta-1-alpha is worldwide one of the most widely used treatments in multiple sclerosis. To our knowledge there is one previous reported case of rhabdomyolysis...... associated with Interferon-beta treatment. Case presentation We describe a 30 year old man with relapsing remitting multiple sclerosis who developed rhabdomyolysis and increased creatine kinase following Interferon-beta-1-alpha therapy. After the medication was discontinued, the patient rapidly improved...... Interferon-beta-1-alpha therapy in patients with multiple sclerosis....

  17. [Solubilization Specificities Interferon beta-1b from Inclusion Bodies].

    Science.gov (United States)

    Zhuravko, A S; Kononova, N V; Bobruskin, A I

    2015-01-01

    A new solubilization method of recombinant interferon beta-1b (IFNβ-1b) from the inclusion bodies was developed. This method allows to extract the target protein selectively in the solutions of different alcohols, such as ethanol, propanol and isopropanol. It was shown that the more effective IFNβ-1b solubilization was achieved in the 55% propanol solution. This method allowed to extract the target protein from inclusion bodies around 85-90%, and significantly reduced Escherichia coli content in the solubilizate, in comparison with standard methods.

  18. {beta} {gamma} porch detector; Detecteur portique {beta} {gamma}

    Energy Technology Data Exchange (ETDEWEB)

    Roulet, R [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires

    1963-07-01

    This device is to be placed at the outside of reactors, hot laboratories and others where radioactive products are treated; it is intended to give the alarm when someone, passing through the porch is greatly contaminated, or carries, without his knowing, a radioactive substance. Being to be used in places where there might be an important ground noise, this device is provided with an automatic offset of this noise; an adjusting system of sensitivity allows to obtain a 15 {mu}Ci in {gamma} and 10 {mu}Ci in {beta} radioactive source, passing through the porch at the normal speed at which man is walking. A battery, set in buffer, allows working of the device, even when current is off. (author) [French] Cet appareil est destine a etre place a la sortie des reacteurs, laboratoires chauds ou autres laboratoires travaillant sur des produits radioactifs; son but est de donner une alarme lorsque quelqu'un, passant sous le portique, presente une forte contamination, ou surtout transporte par inadvertance un corps radioactif. Cet appareil devant etre utilise dans les lieux ou peut regner un bruit de fond important, possede une compensation automatique de ce bruit de fond; un reglage de la sensibilite permet d'obtenir au mieux un declenchement pour une source. de 15 {mu}Ci en {gamma} et 10 {mu}Ci en {beta} passant sous le portique a la vitesse normale d'un homme qui marche. Une batterie montee en tampon permet a l'appareil de fonctionner meme en cas de coupure de courant. (auteur)

  19. Immune activation in multiple sclerosis and interferon-beta therapy

    DEFF Research Database (Denmark)

    Krakauer, Martin

    2007-01-01

    The PhD dissertation emanated from the Danish MS Research Centre, Rigshosptalet, Copenhagen. Multiple sclerosis (MS) is an inflammatory disease of the CNS. Inflammatory responses by T helper (Th)-lymphocytes are characterised by distinct cytokine expression profiles. In MS, activated Th1...... of inflammation or secondary lymphatic organs. Chemokine receptors are differentially expressed in T cells in blood and cerebrospinal fluid, indicating their role for in T-cell-recruitment to the CNS. Interferon (IFN)-beta is a first-line treatment for MS. The mechanism of action is unclear, but probably includes...... changes in lymphocyte activation, cytokine secretion, and trafficking. The aim of the studies was to shed more light on T-cell immunology in MS and IFN-beta treatment, as well as identifying putative biomarkers of treatment response and/or disease activity. In one study we identified a Th-cell subset...

  20. Rhabdomyolysis following interferon-beta treatment in a patient with multiple sclerosis - A case report.

    Science.gov (United States)

    Dalbjerg, Sara Maria; Tsakiri, Anna; Frederiksen, Jette Lautrup

    2016-07-01

    Multiple sclerosis is an inflammatory disease of the central nervous system for which there is currently no cure. Interferon-beta-1-alpha is worldwide one of the most widely used treatments in multiple sclerosis. To our knowledge there is one previous reported case of rhabdomyolysis associated with Interferon-beta treatment. We describe a 30 year old man with relapsing remitting multiple sclerosis who developed rhabdomyolysis and increased creatine kinase following Interferon-beta-1-alpha therapy. After the medication was discontinued, the patient rapidly improved. Clinicians should be aware of the possibility of rhabdomyolysis occurring during Interferon-beta-1-alpha therapy. In cases where patients complain of severe myalgia, and in particular if weakness is reported, creatine kinase activity should be measured to prevent irreversible rhabdomyolysis during Interferon-beta-1-alpha therapy in patients with multiple sclerosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Interferon gamma, interleukin 4 and transforming growth factor beta in experimental autoimmune encephalomyelitis in Lewis rats: dynamics of cellular mRNA expression in the central nervous system and lymphoid cells

    DEFF Research Database (Denmark)

    Issazadeh-Navikas, Shohreh; Mustafa, M; Ljungdahl, A

    1995-01-01

    , the target organ in EAE, cells expressing mRNA for IFN-gamma, first appeared at the onset of clinical signs, i.e., day 10 postimmunization (p.i.), peaked at the height of disease (day 13 p.i.) and then gradually decreased concomitant with recovery. Very few IL-4 mRNA-expressing cells appeared in the spinal...... to limit central nervous system (CNS) inflammation. In lymphoid organs, primed MBP 63-88 reactive T cells showed an interesting time-dependent evolution of their cytokine production in vitro. Thus, early after immunization there was a conspicuous MBP 63-88-induced production of both IFN-gamma and IL-4...... cord with no clear relation to clinical signs or histopathology. In contrast, expression of mRNA for TGF-beta did not increase until day 13 p.i., at height of the disease, shortly preceding recovery. These data are consistent with a disease upregulating role of IFN-gamma, while TGF-beta may act...

  2. Oxidative Modification of Blood Serum Proteins in Multiple Sclerosis after Interferon Beta and Melatonin Treatment

    Directory of Open Access Journals (Sweden)

    Monika Adamczyk-Sowa

    2017-01-01

    Full Text Available Multiple sclerosis (MS is a disease involving oxidative stress (OS. This study was aimed at examination of the effect of melatonin supplementation on OS parameters, especially oxidative protein modifications of blood serum proteins, in MS patients. The study included 11 control subjects, 14 de novo diagnosed MS patients with the relapsing-remitting form of MS (RRMS, 36 patients with RRMS receiving interferon beta-1b (250 μg every other day, and 25 RRMS patients receiving interferon beta-1b plus melatonin (5 mg daily. The levels of N′-formylkynurenine, kynurenine, dityrosine, carbonyl groups, advanced glycation products (AGEs, advanced oxidation protein products (AOPP, and malondialdehyde were elevated in nontreated RRSM patients. N′-Formylkynurenine, kynurenine, AGEs, and carbonyl contents were decreased only in the group treated with interferon beta plus melatonin, while dityrosine and AOPP contents were decreased both in the group of patients treated with interferon beta and in the group treated with interferon beta-1b plus melatonin. These results demonstrate that melatonin ameliorates OS in MS patients supporting the view that combined administration of interferon beta-1b and melatonin can be more effective in reducing OS in MS patients than interferon beta-1b alone.

  3. Increase in neutrophil Fc gamma receptor I expression following interferon gamma treatment in rheumatoid arthritis.

    Science.gov (United States)

    Goulding, N J; Knight, S M; Godolphin, J L; Guyre, P M

    1992-04-01

    The therapeutic potential of interferon gamma (IFN gamma) in a number of disease states is still being explored, but progress is hampered by the lack of a suitable measure of in vivo biological activity. To assess the in vivo biological effects of recombinant human IFN gamma (rhIFN gamma), 14 patients were studied in a randomised, prospective, double blind, placebo controlled trial of this cytokine for the treatment of rheumatoid arthritis. The levels of Fc gamma receptors on peripheral blood neutrophils were measured at baseline and after 21 days of once daily, subcutaneous injections of rhIFN gamma or placebo. An induction of neutrophil Fc gamma receptor type I (Fc gamma RI) was seen in the group of patients receiving recombinant human rhIFN gamma but not in those receiving placebo. No change in the expression of Fc gamma RII or Fc gamma RIII was detected. The amount of induction of Fc gamma RI detected on the neutrophils of patients receiving rhIFN gamma did not correlate with clinical measures of response at either 21 days or at the end of the study (24 weeks). No significant clinical responses were observed in the rhIFN gamma group at these times. These data confirm that the reported in vitro effect of IFN gamma on human neutrophil Fc receptor expression can be reproduced in vivo.

  4. The function of the human interferon-beta 1a glycan determined in vivo

    DEFF Research Database (Denmark)

    Dissing-Olesen, Lasse; Thaysen-Andersen, Morten; Meldgaard, Michael

    2008-01-01

    Recombinant human interferon-beta (rhIFN-beta) is the leading therapeutic intervention shown to change the cause of relapsing-remitting multiple sclerosis, and both a nonglycosylated and a significantly more active glycosylated variant of rhIFN-beta are used in treatment. This study investigates...... into the role of the rhIFN-beta1a glycan and its carbohydrate residues. The possibilities of improving the pharmacological properties of rhIFN-beta1a using glycoengineering are discussed...

  5. Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis

    DEFF Research Database (Denmark)

    Sorensen, Per Soelberg; Ross, Christian; Clemmesen, Katja Maria

    2003-01-01

    Interferon beta is the first-line treatment for relapsing-remitting multiple sclerosis, but the drug can induce neutralising antibodies against itself, which might reduce effectiveness. We aimed to assess the clinical effect of neutralising antibodies....

  6. Product related factors influencing the immunogenicity of interferon beta-1b

    NARCIS (Netherlands)

    Haji Abdolvahab, M.

    2016-01-01

    Therapeutic interferon beta is the first line treatment of relapsing remitting Multiple Sclerosis. However, despite their success in improving patient wellbeing, all IFNβ products encounter a significant problem: immunogenicity. In some patients, IFNβ products induce the formation of antidrug

  7. Higher Serum Uric Acid Levels in Multiple Sclerosis Patients After Longterm Interferon Beta Treatment

    Directory of Open Access Journals (Sweden)

    Toncev Gordana

    2017-10-01

    Full Text Available Interferon beta is a safe and efficacious treatment for relapsing multiple sclerosis (MS. However, there is some evidence that uric acid, a scavenger of peroxynitrite, is involved in MS pathology and that increasing serum uric acid levels might have beneficial therapeutic effects. The aim of this study is to investigate serum uric acid levels in MS patients before and after long-term interferon beta treatment. Blood samples from 101 MS patients (53 receiving interferon beta 1a treatment and 48 receiving interferon beta 1b treatment; 28 male and 73 female; mean age at treatment onset 32,4±7,3 years; mean duration of disease at treatment onset 5,1±3,2 years; mean EDSS 2±1,3 before and after interferon beta treatment (mean treatment duration 3±2 years were analysed. Serum uric acid levels were measured using a quantitative enzymatic assay (Elitech Diagnostic, Sees, France. MS patients had significantly increased serum uric acid levels after treatment compared with those at the beginning of treatment (272,31±78,21 μmol/l vs. 210,17±53,65 μmol/l; p=0,019, Wilcoxon Mann-Whitney U-test. We did not find significant differences in serum uric acid levels between the interferon beta 1a and interferon beta 1b groups (p=0.98. These results indicate that one of the beneficial effects of interferon beta in MS might be based on the elevation of serum uric acid levels as a natural scavenger of peroxynitrite.

  8. Gamma interferon augments Fc gamma receptor-mediated dengue virus infection of human monocytic cells.

    OpenAIRE

    Kontny, U; Kurane, I; Ennis, F A

    1988-01-01

    It has been reported that anti-dengue antibodies at subneutralizing concentrations augment dengue virus infection of monocytic cells. This is due to the increased uptake of dengue virus in the form of virus-antibody complexes by cells via Fc gamma receptors. We analyzed the effects of recombinant human gamma interferon (rIFN-gamma) on dengue virus infection of human monocytic cells. U937 cells, a human monocytic cell line, were infected with dengue virus in the form of virus-antibody complexe...

  9. Beta/gamma test problems for ITS

    International Nuclear Information System (INIS)

    Mei, G.T.

    1993-01-01

    The Integrated Tiger Series of Coupled Electron/Photon Monte Carlo Transport Codes (ITS 3.0, PC Version) was used at Oak Ridge National Laboratory (ORNL) to compare with and extend the experimental findings of the beta/gamma response of selected health physics instruments. In order to assure that ITS gives correct results, several beta/gamma problems have been tested. ITS was used to simulate these problems numerically, and results for each were compared to the problem's experimental or analytical results. ITS successfully predicted the experimental or analytical results of all tested problems within the statistical uncertainty inherent in the Monte Carlo method

  10. Interleukin 12 in part regulates gamma interferon release in human whole blood stimulated with Leptospira interrogans

    NARCIS (Netherlands)

    de Fost, Maaike; Hartskeerl, Rudy A.; Groenendijk, Martijn R.; van der Poll, Tom

    2003-01-01

    Heat-killed pathogenic Leptospira interrogans serovar rachmati induced the production of gamma interferon (IFN-gamma) and the IFN-gamma-inducing cytokines interleukin-12p40 (IL-12p40) and tumor necrosis factor alpha in human whole blood in vitro. The production of IFN-gamma was largely dependent on

  11. Gene expression analysis of interferon-beta treatment in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F.; Datta, P.; Larsen, J.

    2008-01-01

    by treatment with IFN-beta. We use DNA microarrays to study gene expression in 10 multiple sclerosis (MS) patients who began de novo treatment with IFN-beta. After the first injection of IFN-beta, the expression of 74 out of 3428 genes changed at least two-fold and statistically significantly (after Bonferroni......Treatment with interferon-beta (IFN-beta) induces the expression of hundreds of genes in blood mononuclear cells, and the expression of several genes has been proposed as a marker of the effect of treatment with IFN-beta. However, to date no molecules have been identified that are stably induced...

  12. Cardiac arrhythmia with premature ventricular contractures induced by interferon beta in a patient with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Igor Sobol

    2015-03-01

    Full Text Available Multiple sclerosis (MS is an immune-mediated inflammatory and neurodegenerative disease of the central nervous system. Interferon (IFN beta is an active ingredient of five out of twelve disease modifying treatments approved for MS. We report a case of IFN-beta-induced cardiac arrhythmia with premature ventricular contractures in a patient recently diagnosed with MS.

  13. Increased expression of beta 2-microglobulin and histocompatibility antigens on human lymphoid cells induced by interferon

    DEFF Research Database (Denmark)

    Hokland, M; Heron, I; Berg, K

    1982-01-01

    Normal human peripheral blood lymphocytes were incubated in the presence of different concentrations of interferon for various incubation periods. Subsequently, the amount of beta 2-Microglobulin and HLA-A, B and C surface antigens was estimated by means of quantitative immunofluorescence (flow...... cytofluorometry) and by a radioimmunoassay for beta 2-Microglobulin. It was found that the amounts of these MHC antigens increased in a dose and time-dependent way after interferon treatment. Furthermore, the influence of different temperatures on this IFN-induced increase in beta 2-Microglobulin was gradually...

  14. beta. -endorphin augments the cytolytic activity and interferon production of natural killer cells

    Energy Technology Data Exchange (ETDEWEB)

    Mandler, R.N.; Biddison, W.E.; Mandler, R.; Serrate, S.A.

    1986-02-01

    The in vitro effects of the neurohormone ..beta..-endorphin (b-end) on natural killer (NK) activity and interferon (IFN) production mediated by large granular lymphocytes (LGL) were investigated. LGL-enriched fractions from peripheral blood mononuclear cells (PBMC) from normal human volunteers were obtained by fractionation over discontinuous Percoll gradients. LGL were preincubated with or without various concentrations of b-end or the closely related peptides ..cap alpha..-endorphin (a-end), ..gamma..-endorphin (g-end), or D-ALA/sub 2/-..beta..-endorphin (D-ALA/sub 2/-b-end), a synthetic b-end analogue. NK activity was assayed on /sup 51/Cr-labeled K562 target cells. Preincubation of LGL effectors (but not K562 targets) for 2 to 18 hr with concentrations of b-end between 10/sup -7/ M and 10/sup -10/ M produced significant augmentation of NK cytolytic activity (mean percentage increase: 63%). The classic opiate antagonist naloxone blocked the enhancing effect when used at a 100-fold molar excess relative to b-end. These findings demonstrate that b-end enhances NK activity and IFN production of purified LGL, and suggests that b-end might bind to an opioid receptor on LGL that can be blocked by naloxone. These results lend support to the concepts of regulation of the immune response by neurohormones and the functional relationship between the nervous and immune systems.

  15. Low level GAMMA0 spectrometry by beta-gamma coincidence

    International Nuclear Information System (INIS)

    Grigorescu, E.L.; Luca, A.; Razdolescu, A.C.; Ivan, C.

    1999-01-01

    Low level gamma spectrometry has a wide application, especially in environmental monitoring. Two variants, based on a beta-gamma coincidence technique, were studied. The equipment was composed of a beta detector and a Ge(Li) gamma detector (6% - relative efficiency), with the associated electronics. The gamma rays are recorded by the multichannel analyzer (4096 channels) only if the associated beta particles, which precede the gamma transitions, are registered in coincidence. Two types of beta detectors were used: plastic and liquid scintillators. In both cases, an external lead shield of 5 cm thick was used. The integral gamma background (50-1700 KeV) was reduced about 85 and 50 times, respectively. The corresponding MDA (Minimum Detectable Activity) values decreased about 1.5 and (3-7) times, respectively. The 2π sr plastic beta detector was placed on top the Ge(Li). The sample was inserted between the two detectors. The measurement time was 10 4 s. A 4π sr detector, built of the same material, was also studied, but it proved to be less advantageous because the background was reduced only 16 times; for a MDA reduction similar with that of the 2π sr variant, a longer measurement was needed (3.10 4 s). The other type of beta detector used, was a liquid scintillator. The dissolving of the samples in scintillator ensures a 4π sr measurement geometry. The vials with scintillator (10 ml volume) were placed on top the Ge(Li) and visualised by the photocathode of a phototube. This setup was surrounded by an enclosure which prevent the light penetration. The measurement time was 10 4 s. The only difficulty encountered in this low level measurement method is the accurate determination of the beta efficiency. A limitation is the possibility to measure only small mass samples. These variants are more simple and cheaper than others, previously studied. The advantage of the method is obvious when, instead of low MDA values, shorter measurement times are preferred. The

  16. The innovative development in interferon beta treatments of relapsing-remitting multiple sclerosis

    DEFF Research Database (Denmark)

    Madsen, Claus

    2017-01-01

    The introduction of interferon beta therapies more than 20 years ago marked a milestone in the treatment of relapsing-remitting multiple sclerosis (RRMS) with a significant impact on the approach to modern multiple sclerosis (MS) care. Key learnings and perspectives from the early days of disease...... modifying therapies in MS have improved the knowledge base of MS, need for treatment, and patient care. The continuous development of interferons over the past two decades outlines a journey with increased understanding of the pharmacodynamics and pharmacokinetic mechanisms of interferons, leading...

  17. [Expression of gamma interferon during HPV and Chlamydia trachomatis infection in cervical samples].

    Science.gov (United States)

    Colín-Ferreyra, María Del Carmen; Mendieta-Zerón, Hugo; Romero-Figueroa, María Del Socorro; Martínez-Madrigal, Migdania; Martínez-Pérez, Sergio; Domínguez-García, María Victoria

    2015-02-01

    The aim of this study was to mesure the expression of gamma interferon in HPV and Chlamydia trachomatis infection in squamous intraepithelial lesions. Samples from 100 patients diagnosed by colposcopy with or without squamous intraepithelial lesions were used in the present study. Each patient was found to be infected by HPV and C.trachomatis. Relative gamma interferon mRNA expression was assessed using a real-time reverse transcriptase PCR assay (RT-PCR). The relative units of expression of gamma interferon mRNA were 13, 1.8 and 0.3, for HPV and C.trachomatis co-infection, or HPV or C.trachomatis infection, respectively. HPV and C.trachomatis could overstimulate the expression of gamma interferon. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  18. Renal thrombotic microangiopathy caused by interferon beta-1a treatment for multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Mahe J

    2013-08-01

    Full Text Available Julien Mahe,1 Aurélie Meurette,2 Anne Moreau,3 Caroline Vercel,2 Pascale Jolliet1,4 1Clinical Pharmacology Department, Institute of Biology, University Hospital, Nantes, France; 2Clinical Nephrology and Immunology Department, University Hospital, Nantes, France; 3Laboratory of Pathology, University Hospital, Nantes, France; 4EA 4275 Biostatistics, Pharmacoepidemiology and Subjective Measures in Health Sciences, University of Nantes, Nantes, France Abstract: Interferon beta-1a is available as an immunomodulating agent for relapsing forms of multiple sclerosis. Common side effects include flu-like symptoms, asthenia, anorexia, and administration site reaction. Kidney disorders are rarely reported. In this study we describe the case of a woman who has been undergoing treatment with interferon beta-1a for multiple sclerosis for 5 years. She developed a hemolytic-uremic syndrome with intravascular hemolysis in a context of severe hypertension. A kidney biopsy showed a thrombotic microangiopathy. This observation highlights an uncommon side effect of long-term interferon beta-1a therapy. Pathophysiological mechanisms leading to this complication might be explained by the antiangiogenic activity of interferon. Keywords: thrombotic microangiopathy, interferon beta, hemolytic-uremic syndrome, antiangiogenic activity

  19. Interferon-Beta in Pediatric Multiple Sclerosis Patients: Safety in Short-Term Prescription

    Directory of Open Access Journals (Sweden)

    Amir Hadi Maghzi

    2012-02-01

    Full Text Available Introduction: None of the approved immunomodulatory drugs in adults Multiple Sclerosis (MS patients have been officially approved for the pediatric patients and are currently used off-label in this population. Objectives: In this study, we evaluated the effectiveness and tolerability of intramuscular interferon beta1-a (Avonex® and subcutaneously injected interferon beta1-b (Betaferon® in children with definite relapsing-remitting MS (RRMS. Thirteen patients aged younger than 16, who were recently diagnosed with definite RRMS according to the McDonalds criteria, were enrolled in this study. Six patients were treated with Avonex® 30 μg, intramuscularly every week, and seven patients were treated with Betaferon® 250 μg, subcutaneously every other day. All patients were treated with adult doses; initially interferon-beta was prescribed with half dose, and it was increased to full adult dose steadily. Results: Eleven girls and two boys, mean (SD age of 14.7 (1.9 years, were studied. Following nine months of using interferon-beta, nine patients (69.2% had no relapses and the remaining four, experienced only one relapse. The mean EDSS score was decreased significantly after the study period. Conclusion: The present study provides reasonable data for the use of interferon-beta in Pediatric MS due to lack of short-term complications and safety. Studies with larger sample size and longer follow up duration are required to shed light on the long term impact of the interferon-beta therapy in children.

  20. Development of a lion-specific interferon-gamma assay.

    Science.gov (United States)

    Maas, M; van Kooten, P J S; Schreuder, J; Morar, D; Tijhaar, E; Michel, A L; Rutten, V P M G

    2012-10-15

    The ongoing spread of bovine tuberculosis (BTB) in African free-ranging lion populations, for example in the Kruger National Park, raises the need for diagnostic assays for BTB in lions. These, in addition, would be highly relevant for zoological gardens worldwide that want to determine the BTB status of their lions, e.g. for translocations. The present study concerns the development of a lion-specific IFN-γ assay, following the production and characterization of monoclonal antibodies specific for lion interferon-gamma (IFN-γ). Recombinant lion IFN-γ (rLIFN-γ) was produced in mammalian cells and used to immunize mice to establish hybridoma cell lines producing monoclonal antibodies. These were used to develop a sensitive, lion IFN-γ-specific capture ELISA, able to detect rLIFN-γ to the level of 160 pg/ml. Recognition of native lion IFN-γ was shown in an initial assessment of supernatants of mitogen stimulated whole blood cultures of 11 known BTB-negative lions. In conclusion, the capture ELISA shows potential as a diagnostic assay for bovine tuberculosis in lions. Preliminary results also indicate the possible use of the test for other (feline) species. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Interferon Gamma in African Trypanosome Infections: Friends or Foes?

    Science.gov (United States)

    Wu, Hui; Liu, Gongguan; Shi, Meiqing

    2017-01-01

    African trypanosomes cause fatal infections in both humans and livestock. Interferon gamma (IFN-γ) plays an essential role in resistance to African trypanosomes. However, increasing evidence suggests that IFN-γ, when excessively synthesized, also induces immunopathology, enhancing susceptibility to the infection. Thus, production of IFN-γ must be tightly regulated during infections with African trypanosomes to ensure that a robust immune response is elicited without tissue destruction. Early studies have shown that secretion of IFN-γ is downregulated by interleukin 10 (IL-10). More recently, IL-27 has been identified as a negative regulator of IFN-γ production during African trypanosome infections. In this review, we discuss the current state of our understanding of the role of IFN-γ in African trypanosome infections. We have focused on the cellular source of IFN-γ, its beneficial and detrimental effects, and mechanisms involved in regulation of its production, highlighting some recent advances and offering some perspectives on future directions.

  2. Gamma Interferon Release Assays for Detection of Mycobacterium tuberculosis Infection

    Science.gov (United States)

    Denkinger, Claudia M.; Kik, Sandra V.; Rangaka, Molebogeng X.; Zwerling, Alice; Oxlade, Olivia; Metcalfe, John Z.; Cattamanchi, Adithya; Dowdy, David W.; Dheda, Keertan; Banaei, Niaz

    2014-01-01

    SUMMARY Identification and treatment of latent tuberculosis infection (LTBI) can substantially reduce the risk of developing active disease. However, there is no diagnostic gold standard for LTBI. Two tests are available for identification of LTBI: the tuberculin skin test (TST) and the gamma interferon (IFN-γ) release assay (IGRA). Evidence suggests that both TST and IGRA are acceptable but imperfect tests. They represent indirect markers of Mycobacterium tuberculosis exposure and indicate a cellular immune response to M. tuberculosis. Neither test can accurately differentiate between LTBI and active TB, distinguish reactivation from reinfection, or resolve the various stages within the spectrum of M. tuberculosis infection. Both TST and IGRA have reduced sensitivity in immunocompromised patients and have low predictive value for progression to active TB. To maximize the positive predictive value of existing tests, LTBI screening should be reserved for those who are at sufficiently high risk of progressing to disease. Such high-risk individuals may be identifiable by using multivariable risk prediction models that incorporate test results with risk factors and using serial testing to resolve underlying phenotypes. In the longer term, basic research is necessary to identify highly predictive biomarkers. PMID:24396134

  3. Interferon-gamma (IFN-gamma) treatment decreases the inflammatory response in chronic Pseudomonas aeruginosa pneumonia in rats

    DEFF Research Database (Denmark)

    Johansen, H K; Hougen, H P; Rygaard, J

    1996-01-01

    In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF), we studied whether the inflammatory response could be altered by intraperitoneal treatment with recombinant rat interferon-gamma (rrIFN-gamma). Rats were treated either before or after intratracheal ch...

  4. Effectiveness of interferon-beta and temozolomide combination therapy against temozolomide-refractory recurrent anaplastic astrocytoma

    Directory of Open Access Journals (Sweden)

    Arai Hajime

    2007-08-01

    Full Text Available Abstract Background Malignant gliomas recur even after extensive surgery and chemo-radiotherapy. Although a relatively novel chemotherapeutic agent, temozolomide (TMZ, has demonstrated promising activity against recurrent glioma, the effects last only a few months and drug resistance develops thereafter in most cases. Induction of O6-methylguanine-DNA methyltransferase (MGMT in tumors is considered to be responsible for resistance to TMZ. Interferon-beta has been reported to suppress MGMT in an experimental glioma model. Here we report a patient with TMZ-refractory anaplastic astrocytoma (AA who was treated successfully with a combination of interferon-beta and TMZ. Case presentation A patient with recurrent AA after radiation-chemotherapy and stereotactic radiotherapy was treated with TMZ. After 6 cycles, the tumor became refractory to TMZ, and the patient was treated with interferon-beta at 3 × 106 international units/body, followed by 5 consecutive days of 200 mg/m2 TMZ in cycles of 28 days. After the second cycle the tumor decreased in size by 50% (PR. The tumor showed further shrinkage after 8 months and the patient's KPS improved from 70% to 100%. The immunohistochemical study of the initial tumor specimen confirmed positive MGMT protein expression. Conclusion It is considered that interferon-beta pre-administration increased the TMZ sensitivity of the glioma, which had been refractory to TMZ monotherapy.

  5. Long-term impact of interferon beta-1b in patients with CIS

    DEFF Research Database (Denmark)

    Edan, G; Kappos, L; Montalbán, X

    2014-01-01

    OBJECTIVE: To examine the long-term impact of early treatment initiation of interferon beta-1b (IFNB1b, Betaferon/Betaseron) in patients with a first event suggestive of multiple sclerosis (MS). METHODS: In the original placebo-controlled phase of BENEFIT, patients were randomised to IFNB1b 250 μg...

  6. Evaluation of Interferon-gamma Application for Recognition of Patients Afflicted by Non-healing Cutaneous Leishmaniasis

    OpenAIRE

    Mohammad Moafi; Hossein Rezvan; Roya Sherkat; Sayyed Hamid Zarkesh-Esfahani; Roya Taleban; Ali Asilian; Mohammad Ali Nilforoushzadeh; Fariba Jaffary; Marjan Mansourian; Fatemeh Sokhanvari; Nazli Ansari

    2017-01-01

    Introduction:Different studies undertaken in the animal modeling show that Interferon-gamma deficiency impairs healing process of Leishmania infection. It seems that the level of Interferon-gamma production could also affect the healing duration of Leishmania lesion in humans. The current study aims to investigate the possibility of Interferon-gamma application for recognition of cases afflicted by non-healing Leishmaniasis. Materials and methods: Peripheral blood mononuclear cells (PBMCs) of...

  7. Interferon gamma peptidomimetic targeted to hepatic stellate cells ameliorates acute and chronic liver fibrosis in vivo

    NARCIS (Netherlands)

    Bansal, Ruchi; Prakash, Jai; De Ruiter, Marieke; Poelstra, Klaas

    2014-01-01

    Hepatic stellate cells play a crucial role in the pathogenesis of hepatic fibrosis. Thus, pharmacological inhibition of pro-fibrotic activities of these cells might lead to an effective therapy for this disease. Among the potent antifibrotics, interferon gamma (IFN gamma), a proinflammatory

  8. Evaluation of Gamma Interferon and Antibody Tuberculosis Tests in Alpacas

    Science.gov (United States)

    Holder, Tom; Clifford, Derek; Dexter, Ian; Brewer, Jacky; Smith, Noel; Waring, Laura; Crawshaw, Tim; Gillgan, Steve; Lyashchenko, Konstantin; Lawrence, John; Clarke, John; de la Rua-Domenech, Ricardo; Vordermeier, Martin

    2012-01-01

    We describe the performance of cell-based and antibody blood tests for the antemortem diagnosis of tuberculosis (TB) in South American camelids (SAC). The sensitivity and specificity of the gamma interferon (IFN-γ) release assay, two lateral flow rapid antibody tests (Stat-Pak and Dual Path Platform [DPP]), and two enzyme-linked immunosorbent assay (ELISA)-based antibody tests (Idexx and Enferplex) were determined using diseased alpacas from Mycobacterium bovis culture-confirmed breakdown herds and TB-free alpacas from geographical areas with no history of bovine TB, respectively. Our results show that while the sensitivities of the IFN-γ and antibody tests were similar (range of 57.7% to 66.7%), the specificity of the IFN-γ test (89.1%) was lower than those of any of the antibody tests (range of 96.4% to 97.4%). This lower specificity of the IFN-γ test was at least in part due to undisclosed Mycobacterium microti infection in the TB-free cohort, which stimulates a positive purified protein derivative (PPD) response. The sensitivity of infection detection could be increased by combining two antibody tests, but even the use of all four antibody tests failed to detect all diseased alpacas. These antibody-negative alpacas were IFN-γ positive. We found that the maximum sensitivity could be achieved only by the combination of the IFN-γ test with two antibody tests in a “test package,” although this resulted in decreased specificity. The data from this evaluation of tests with defined sensitivity and specificity provide potential options for antemortem screening of SAC for TB in herd breakdown situations and could also find application in movement testing and tracing investigations. PMID:22914362

  9. Immunomodulatory intervention with Gamma interferon in mice with sepsis.

    Science.gov (United States)

    Wang, Yu; Kong, Bing-Bing; Yang, Wen-Ping; Zhao, Xin; Zhang, Rong

    2017-09-15

    Sepsis-triggered immune paralysis including T-cell dysfunction increase susceptibility to infection. Gamma interferon (IFNg) exert beneficial effects in patients with sepsis. Herein, we speculated that IFNg may attenuate T-cell dysfunction induced by sepsis, although the mechanisms remain elusive. To test this hypothesis, we used a model based on cecal ligation and puncture (CLP) to induce sepsis in mice. Male C57BL/6 mice were pretreated with recombinant human IFNg (0.01μg/g of body weight) before CLP. The immunophenotyping of cell surface receptor expression, and regulatory T cells (CD4+CD25+Foxp3+) were quantified by flow cytometry. Immunohistochemical staining was performed to evaluate the loss of immune effector cells. Formation of IFNg and interleukin 4 (IL-4) in the spleen and plasma levels of TNF-α, IL-6, high-mobility group box 1 (HMGB1) were determined using enzyme-linked immunosorbent assay. IFNg markedly inhibited the reduction in cytokine secretion from lipopolysaccharide (LPS)-stimulated splenocytes. IFNg-treated mices had significantly decreased percentages of programmed cell death 1 (PD-1) receptors, increased the percentages of positive costimulatory receptor CD28 on CD4 T cells expressing. IFNg markedly reduced T-cell apoptosis through upregulating the expression of Bcl-2. CLP-induced formation of regulatory T cells in the spleen was abolished in IFNg -treated mices. Moreover, IFNg treatment reduced plasma levels of TNF-α, IL-6, HMGB1. IFNg can be a powerful regulator of immune function under sepsis conditions. Therefore, targeted immune-enhancement with IFNg may be a valid therapeutic approach in sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Two-site sandwich radioimmunoassay of human gamma interferon with monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, E; Imai, M; Usuda, S; Tachibana, K; Okamoto, H; Ohike, Y; Nakamura, T; Miyakawa, Y; Mayumi, M [Jichi Medical School, Minamikawachi, Tochigi (Japan)

    1985-03-18

    Two monoclonal antibodies were raised against human gamma interferon (IFN-..gamma..) derived from E. coli harboring the recombinant cDNA for IFN-..gamma.., and one against a synthetic peptide representing its C-terminus amino acid sequence of 20 residues. The monoclonal antibody against the synthetic peptide reacted either with IFN-..gamma.. or the synthetic peptide. One monoclonal anti-IFN-..gamma.. did not react with the synthetic peptide, while the other showed a weak binding with the peptide. A 2-site '1-step' radioimmunoassay was developed. The assay was rapid with a sensitivity capable of detecting a few ng/ml of IFN-..gamma...

  11. The CXC chemokines gamma interferon (IFN-gamma)-inducible protein 10 and monokine induced by IFN-gamma are released during severe melioidosis

    NARCIS (Netherlands)

    Lauw, F. N.; Simpson, A. J.; Prins, J. M.; van Deventer, S. J.; Chaowagul, W.; White, N. J.; van der Poll, T.

    2000-01-01

    Gamma interferon (IFN-gamma)-inducible protein 10 (IP-10) and monokine induced by IFN-gamma (Mig) are related CXC chemokines which bind to the CXCR3 receptor and specifically target activated T lymphocytes and natural killer (NK) cells. The production of IP-10 and Mig by various cell types in vitro

  12. Recommendations for clinical use of data on neutralising antibodies to interferon-beta therapy in multiple sclerosis

    DEFF Research Database (Denmark)

    Polman, Chris H; Bertolotto, Antonio; Deisenhammer, Florian

    2010-01-01

    in MS and NAbs to interferon-beta therapy convened in Amsterdam, Netherlands, under the auspices of the Neutralizing Antibodies on Interferon beta in Multiple Sclerosis consortium, a European-based project of the 6th Framework Programme of the European Commission, to review and discuss data on NAbs......The identification of factors that can affect the efficacy of immunomodulatory drugs in relapsing-remitting multiple sclerosis (MS) is important. For the available interferon-beta products, neutralising antibodies (NAb) have been shown to affect treatment efficacy. In June, 2009, a panel of experts...... and their practical consequences for the treatment of patients with MS on interferon beta. The panel believed that information about NAbs and other markers of biological activity of interferons (ie, myxovirus resistance protein A [MxA]) can be integrated with clinical and imaging indicators to guide individual...

  13. The effect of beta-interferon therapy on myelin basic protein-elicited CD4+ T cell proliferation and cytokine production in multiple sclerosis

    DEFF Research Database (Denmark)

    Hedegaard, Chris J; Krakauer, Martin; Bendtzen, Klaus

    2008-01-01

    Interferon (IFN)-beta therapy has well-established clinical benefits in multiple sclerosis (MS), but the underlying modulation of cytokine responses to myelin self-antigens remains poorly understood. We analysed the CD4+ T cell proliferation and cytokine responses elicited by myelin basic protein...... (MBP) and a foreign recall antigen, tetanus toxoid (TT), in mononuclear cell cultures from fourteen MS patients undergoing IFN-beta therapy. The MBP-elicited IFN-gamma-, TNF-alpha- and IL-10 production decreased during therapy (p...

  14. Whole-exome sequencing reveals a rare interferon gamma receptor 1 mutation associated with myasthenia gravis.

    Science.gov (United States)

    Qi, Guoyan; Liu, Peng; Gu, Shanshan; Yang, Hongxia; Dong, Huimin; Xue, Yinping

    2018-04-01

    Our study is aimed to explore the underlying genetic basis of myasthenia gravis. We collected a Chinese pedigree with myasthenia gravis, and whole-exome sequencing was performed on the two affected siblings and their parents. The candidate pathogenic gene was identified by bioinformatics filtering, which was further verified by Sanger sequencing. The homozygous mutation c.G40A (p.V14M) in interferon gamma receptor 1was identified. Moreover, the mutation was also detected in 3 cases of 44 sporadic myasthenia gravis patients. The p.V14M substitution in interferon gamma receptor 1 may affect the signal peptide function and the translocation on cell membrane, which could disrupt the binding of the ligand of interferon gamma and antibody production, contributing to myasthenia gravis susceptibility. We discovered that a rare variant c.G40A in interferon gamma receptor 1 potentially contributes to the myasthenia gravis pathogenesis. Further functional studies are needed to confirm the effect of the interferon gamma receptor 1 on the myasthenia gravis phenotype.

  15. Review of the recombinant human interferon gamma as an immunotherapeutic: Impacts of production platforms and glycosylation.

    Science.gov (United States)

    Razaghi, Ali; Owens, Leigh; Heimann, Kirsten

    2016-12-20

    Human interferon gamma is a cytokine belonging to a diverse group of interferons which have a crucial immunological function against mycobacteria and a wide variety of viral infections. To date, it has been approved for treatment of chronic granulomatous disease and malignant osteopetrosis, and its application as an immunotherapeutic agent against cancer is an increasing prospect. Recombinant human interferon gamma, as a lucrative biopharmaceutical, has been engineered in different expression systems including prokaryotic, protozoan, fungal (yeasts), plant, insect and mammalian cells. Human interferon gamma is commonly expressed in Escherichia coli, marketed as ACTIMMUNE ® , however, the resulting product of the prokaryotic expression system is unglycosylated with a short half-life in the bloodstream; the purification process is tedious and makes the product costlier. Other expression systems also did not show satisfactory results in terms of yields, the biological activity of the protein or economic viability. Thus, the review aims to synthesise available information from previous studies on the production of human interferon gamma and its glycosylation patterns in different expression systems, to provide direction to future research in this field. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Temporary increase in serum beta 2-microglobulin during treatment with interferon-alpha for AIDS-associated Kaposi's sarcoma

    NARCIS (Netherlands)

    de Wit, R.; Bakker, P. J.; Reiss, P.; Hoek, F. J.; Lange, J. M.; Goudsmit, J.; Veenhof, K. H.

    1990-01-01

    Beta 2-microglobulin (beta 2-M) levels were determined in the serum of 24 patients treated with high-dose human recombinant interferon-alpha (IFN alpha) for AIDS-associated Kaposi's sarcoma. There was a significant increase in serum beta 2-M levels, irrespective of the response to treatment.

  17. The effect of interferon-{beta} on mouse neural progenitor cell survival and differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Hirsch, Marek [Neurology Department, University of Vermont College of Medicine, Burlington, VT (United States); Knight, Julia [Neuroscience Department, University of Vermont College of Medicine, Burlington, VT (United States); Tobita, Mari; Soltys, John; Panitch, Hillel [Neurology Department, University of Vermont College of Medicine, Burlington, VT (United States); Mao-Draayer, Yang, E-mail: yang.mao-draayer@vtmednet.org [Neurology Department, University of Vermont College of Medicine, Burlington, VT (United States)

    2009-10-16

    Interferon-{beta} (IFN-{beta}) is a mainstay therapy for relapse-remitting multiple sclerosis (MS). However, the direct effects of IFN-{beta} on the central nervous system (CNS) are not well understood. To determine whether IFN-{beta} has direct neuroprotective effects on CNS cells, we treated adult mouse neural progenitor cells (NPCs) in vitro with IFN-{beta} and examined the effects on proliferation, apoptosis, and differentiation. We found that mouse NPCs express high levels of IFN{alpha}/{beta} receptor (IFNAR). In response to IFN-{beta} treatment, no effect was observed on differentiation or proliferation. However, IFN-{beta} treated mouse NPCs demonstrated decreased apoptosis upon growth factor withdrawal. Pathway-specific polymerase chain reaction (PCR) arrays demonstrated that IFN-{beta} treatment upregulated the STAT 1 and 2 signaling pathway, as well as GFRA2, NOD1, Caspases 1 and 12, and TNFSF10. These results suggest that IFN-{beta} can directly affect NPC survival, possibly playing a neuroprotective role in the CNS by modulating neurotrophic factors.

  18. Stimulation of Inducible Nitric Oxide Synthase Expression by Beta Interferon Increases Necrotic Death of Macrophages upon Listeria monocytogenes Infection▿

    OpenAIRE

    Zwaferink, Heather; Stockinger, Silvia; Reipert, Siegfried; Decker, Thomas

    2008-01-01

    Murine macrophage death upon infection with Listeria monocytogenes was previously shown to be increased by beta interferon, produced by the infected cells. We saw that interferon-upregulated caspase activation or other interferon-inducible, death-associated proteins, including TRAIL, protein kinase R, and p53, were not necessary for cell death. Macrophage death was reduced when inducible nitric oxide synthase (iNOS) was inhibited during infection, and iNOS-deficient macrophages were less susc...

  19. Erupção acneiforme aguda induzida por interferon beta-1b durante tratamento para esclerose múltipla Acute acneiform eruption induced by interferon beta-1b during treatment for multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Dário Júnior de Freitas Rosa

    2011-04-01

    Full Text Available Esclerose múltipla é uma doença inflamatória desmielinizante, com presumida origem autoimune, que afeta o sistema nervoso central. A principal modalidade terapêutica é baseada no uso de imunomoduladores, como o interferon beta, que são geralmente bem tolerados. As manifestações cutâneas secundárias ao interferon beta-1b são representadas, na maioria das vezes, por reações no local de sua aplicação subcutânea. Descrevemos o caso de uma paciente do sexo feminino que desenvolveu um quadro de erupção acneiforme pelo interferon beta-1b.Multiple sclerosis is an inflammatory demyelinating disease of presumed autoimmune origin that affects the central nervous system. The main form of therapy is based on the use of immunomodulators such as interferon beta, which are usually well tolerated. Skin manifestations resulting from treatment with interferon beta-1b consist principally of reactions at the site of subcutaneous application of the drug. The present case report describes a female patient who developed an acneiform eruption resulting from treatment with interferon beta-1b.

  20. Interferon-beta in multiple sclerosis. Can we control its costs?

    Science.gov (United States)

    Tolley, K H; Whynes, D K

    1997-03-01

    The recent licensing of interferon-beta for use in patients with multiple sclerosis has caused concern, in view of the equivocal evidence of efficacy, pressure of public expectation towards its use and the high expected cost if widespread use were to be sanctioned. Whether such alarm is justified remains a moot point. Owing to the limited range of circumstances of proven efficacy and the lack of cost-effectiveness data, it remains unclear whether sanctioned usage will proliferate to the anticipated extent. Unit costs may well fall in the future owing to competition in the pharmaceutical market. Interferon-beta is simply one example of a growing trend in actively promoted high-cost preparations over which rationing decisions will have to be reached.

  1. Gender effects on treatment response to interferon-beta in multiple sclerosis

    DEFF Research Database (Denmark)

    Magyari, M; Koch-Henriksen, N; Laursen, B

    2014-01-01

    BACKGROUND: Gender appears to play a role in incidence and disease course of multiple sclerosis (MS). OBJECTIVE: The objective was to determine whether male and female patients with MS respond differently to interferon-beta treatment in terms of reduction in relapse rates. METHODS: We included all....... Patients served as their own controls, and relapse rates were compared between NAb-negative and NAb-positive periods. RESULTS: NAbs significantly abrogated the interferon-beta treatment efficacy in both genders. The all-over women:men relapse rate ratio irrespective of NAb status was 1.47 (95%CI; 1.......28-1.68). In a generalized linear Poisson models analysis with relapse counts as response variable, the main effects NAbs, sex, age at treatment start and number of relapses in 2 years before treatment start were strongly significant, but the effect of NAbs on relapse rates did not differ significantly between men and women...

  2. Interferon-gamma treatment kinetics among patients with active ...

    African Journals Online (AJOL)

    Introduction: Interferon-γ (IFN-γ) is essential for defence against Mycobacterium tuberculosis; however, levels in patients with active tuberculosis (TB) and changes during treatment have not been documented in our tuberculosis patients in Nigeria, hence this study has been carried out. Objective: To determine variations, ...

  3. Activation of the human beta interferon gene by the adenovirus type 12 E1B gene

    International Nuclear Information System (INIS)

    Shiroki, K.; Toth, M.

    1988-01-01

    The transcription of endogenous beta interferon mRNA was activated in human embryo kidney (HEK) cells infected with adenovirus 12 (Ad12) but was activated only inefficiently or not at all in HEK cells infected with Ad5 and rc-1 (Ad5 dl312 containing the Ad12 E1A region). The analysis with Ad12 mutants showed that Ad12 E1B products, especially the 19K protein, were important for the expression of the endogenous beta interferon gene and Ad12 E1A products were not involved in the expression. The expression of exogeneously transfected pIFN-CAT (a hybrid plasmid having the human beta interferon promoter fused with the CAT gene) was activated in HEK and chicken embryo fibroblast (CEF) cells infected with either Ad12 or Ad5. The analysis of cotransfection of CEF cells with pIFN-CAT and plasmids containing fragments of Ad12 or Ad5 DNA showed that Ad12 or Ad5 E1B (possibly the 19K protein) was and E1A was not involved in the expression of the exogenous pIFN-CAT

  4. Enhanced gamma interferon responses of mouse spleen cells following immunotherapy for tuberculosis relapse.

    Science.gov (United States)

    Gil, Olga; Vilaplana, Cristina; Guirado, Evelyn; Díaz, Jorge; Cáceres, Neus; Singh, Mahavir; Cardona, Pere-Joan

    2008-11-01

    Gamma interferon responses of spleen cells in mice were examined during postchemotherapy relapse of intraperitoneally induced latent tuberculous infection. The mycobacterial extract RUTI, which prevented the relapse, significantly enhanced the immune responses to secreted and structural recombinant mycobacterial antigens, suggesting that RUTI-mediated protection was mediated by activated T cells.

  5. Comparison of two interferon-gamma assays and tuberculin skin test for tracing tuberculosis contacts

    NARCIS (Netherlands)

    Arend, Sandra M.; Thijsen, Steven F. T.; Leyten, Eliane M. S.; Bouwman, John J. M.; Franken, Willeke P. J.; Koster, Ben F. P. J.; Cobelens, Frank G. J.; van Houte, Arend-Jan; Bossink, Ailko W. J.

    2007-01-01

    The tuberculin skin test (TST) has low specificity. QuantiFERON-TB Gold (QFT-G) and T-SPOT.TB are based on interferon (IFN)-gamma responses to Mycobacterium tuberculosis-specific antigens. A novel in-tube format of QFT-G (QFT-GIT) offers logistical advantages. To compare TST, QFT-GIT, and T-SPOT.TB

  6. Use of the johnin PPD interferon-gamma assay in control of bovine paratuberculosis

    DEFF Research Database (Denmark)

    Jungersen, Gregers; Mikkelsen, Heidi; Grell, Susanne N.

    2012-01-01

    Although the interferon-gamma (IFN-γ) assay for measurements of cell-mediated immune (CMI) responses to paratuberculosis PPD (johnin) has been available for close to 20 years, the assay has not yet emerged as the long desired test to identify infected animals at an early time point. Among other...

  7. Interferon gamma peptidomimetic targeted to hepatic stellate cells ameliorates acute and chronic liver fibrosis in vivo

    NARCIS (Netherlands)

    Bansal, Ruchi; Prakash, Jai; de Ruiter, Marieke; Poelstra, Klaas

    2014-01-01

    Hepatic stellate cells play a crucial role in the pathogenesis of hepatic fibrosis. Thus, pharmacological inhibition of pro-fibrotic activities of these cells might lead to an effective therapy for this disease. Among the potent anti-fibrotics, interferon gamma (IFNγ), a proinflammatory cytokine, is

  8. Enzyme-linked immunospot: an alternative method for the detection of interferon gamma in Johne's disease

    DEFF Research Database (Denmark)

    Begg, Douglas J.; de Silva, Kumudika; Bosward, Katrina

    2009-01-01

    To date, the sensitivity of the interferon gamma (IFN-) enzyme-linked immunosorbent assay (ELISA) to detect Johne's disease (JD) has been poor, especially in the early stages of disease. To improve the sensitivity of IFN- detection in the early stages of infection, an alternate assay needs to be ...

  9. Polymorphisms in an interferon-gamma receptor-1 gene marker and susceptibility to periodontitis

    NARCIS (Netherlands)

    Fraser, DA; Loos, BG; Boman, U; van Winkelhoff, AJ; van der Velden, U; Schenck, K; Dembic, Z

    2003-01-01

    Chronic marginal periodontitis is an inflammatory condition in which the supporting tissues of the teeth are destroyed. Interferon (IFN)-gamma is a cytokine that plays a pivotal role in the defense against infection, and mutations in the gene coding for the ligand binding chain (alpha, RI) of the

  10. Diminished interferon-gamma production and responsiveness after endotoxin administration to healthy humans

    NARCIS (Netherlands)

    Weijer, Sebastiaan; Lauw, Fanny N.; Branger, Judith; van den Blink, Bernt; van der Poll, Tom

    2002-01-01

    To obtain insight in the capacity of the lipopolysaccharide (LPS)-tolerant host to produce interferon (IFN)-gamma and to respond to this cytokine, whole blood was obtained from healthy humans before and 4 h after intravenous injection of LPS (4 ng/kg) and stimulated ex vivo. LPS exposure in vivo

  11. Microscopic beta and gamma data for decay-heat needs

    International Nuclear Information System (INIS)

    Dickens, J.K.

    1983-01-01

    Microscopic beta and gamma data for decay-heat needs are defined as absolute-intensity spectral distributions of beta and gamma rays following radioactive decay of radionuclides created by, or following, the fission process. Four well-known evaluated data files, namely the US ENDF/B-V, the UK UKFPDD-2, the French BDN (for fission products), and the Japanese JNDC Nuclear Data Library, are reviewed. Comments regarding the analyses of experimental data (particularly gamma-ray data) are given; the need for complete beta-ray spectral measurements is emphasized. Suggestions on goals for near-term future experimental measurements are presented. 34 references

  12. Maternal plasma concentrations of beta-lipotrophin, beta-endorphin and gamma-lipotrophin throughout pregnancy.

    Science.gov (United States)

    Browning, A J; Butt, W R; Lynch, S S; Shakespear, R A

    1983-12-01

    Plasma beta-LPH, beta-EP and gamma-LPH concentrations were measured by radioimmunoassay in 10 pregnant women from 12 weeks gestation until term and in nine women in the early follicular phase of the cycle. There was a progressive and significant rise in the concentration of all three peptides throughout pregnancy and by 32 weeks the concentrations of beta-LPH and beta-EP were greater than the corresponding concentrations in the follicular phase: gamma-LPH was greater than in the follicular phase by the end of pregnancy in those women who were delivered after 40 weeks. The ratio of beta-LPH to gamma-LPH did not change significantly throughout pregnancy, but there was a progressive fall in the beta-LPH/beta-EP ratio. The possible presence of a 'big LPH' to explain this finding is discussed.

  13. Interferon-gamma regulates oxidative stress during experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Espejo, Carmen; Penkowa, Milena; Sáez-Torres, Irene

    2002-01-01

    disease eliciting secretion of proinflammatory cytokines like IFN-gamma or TNF-alpha, and it has been suggested that cytokine-induced oxidative stress could have a role in EAE neuropathology. However, the individual roles of these and other cytokines in the pathogenesis of the disease are still uncertain....... Here we analyze the role of IFN-gamma during EAE by using both IFN-gamma receptor-knockout (IFN-gamma R(-/-)) and wild-type mice, both strains immunized with peptide 40-55 from rat myelin oligodendrocyte glycoprotein. The levels of oxidative stress were determined through the analysis...... of immunoreactivity for inducible NO synthase, nitrotyrosine, and malondialdehyde, as well as through the expression of the tissue-protective antioxidant factors metallothionein I+II (MT-I+II). We also examined the number of cells undergoing apoptosis as judged by using the TUNEL technique. The levels of oxidative...

  14. Gamma ampersand beta-gamma storm water monitor operability

    International Nuclear Information System (INIS)

    Tshiskiku, E.M.

    1993-01-01

    High Level Waste (HLW) facilities have nine storm water monitors that monitor storm water run off from different process areas for Cesium 137, a Gamma emitter. F - Area has three monitors: 907-2F, 907-3F and 907-4F while H - Area has six monitors: 907-2H, 907-3H, 907-4H, 907-5H, 907-6H and 907-7H (See attachments number-sign 1, number-sign 2 and number-sign 3 for location). In addition to monitoring for Cesium, 907-6H and 907-7H monitor for Strontium-90, a Beta emitter. Each monitor is associated with one of the following diversion gate encasements 907-1H, 241-15H, 241-51H, 907-1F or 241-23F. Normal flow of storm water from these diversion gate encasements is to the Four Mile Creek. When a storm water monitor detects radioactivity at a level exceeding the Four Mile Creek discharge limit, the monitor causes repositioning of the associated diversion gate to discharge to the H - Area retention basin 281-8H or the F - Area retention basin 281-8F. In response to recent OSR interpretation of storm water monitor calibration requirements, this report is provided to document operability and accuracy of radiation detection

  15. Behavior of a cloned murine interferon alpha/beta receptor expressed in homospecific or heterospecific background.

    Science.gov (United States)

    Uzé, G; Lutfalla, G; Bandu, M T; Proudhon, D; Mogensen, K E

    1992-05-15

    A murine interferon (IFN) alpha/beta receptor was cloned from the IFN-sensitive L1210 cell line on the basis of its homology with the human receptor. A combination of methods that includes the screening of random-primed and oligo(dT)-primed cDNA libraries and polymerase chain reactions with a single-side specificity was used. At the amino acid level, the murine IFN-alpha/beta shows 46% identity with its human counterpart. Both human WISH cells presenting a low sensitivity to mouse IFN and a murine L1210 mutant subline that does not express the receptor have been stably transfected with the murine IFN-alpha/beta receptor. Whereas transfected human cells became sensitive to a limited number of mouse IFN-alpha/beta subtypes, the transfected murine L1210 mutant was found to be fully complemented and became sensitive to all mouse IFN-alpha/beta subtypes tested, including those that were not active on transfected human cells. These results strongly suggest that the receptor described here is implicated in the mediation of the activities of all murine IFN-alpha/beta subtypes.

  16. Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Shirani, Afsaneh; Zhao, Yinshan; Karim, Mohammad Ehsanul; Evans, Charity; Kingwell, Elaine; van der Kop, Mia L; Oger, Joel; Gustafson, Paul; Petkau, John; Tremlett, Helen

    2012-07-18

    Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts. The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0

  17. [Adenovirus-mediated canine interferon-gamma expression and its antiviral activity against canine parvovirus].

    Science.gov (United States)

    Zhang, Kao; Jin, Huijun; Zhong, Fei; Li, Xiujin; Neng, Changai; Chen, Huihui; Li, Wenyan; Wen, Jiexia

    2012-11-04

    To construct recombinant adenovirus containing canine interferon-gamma (cIFN-gamma) gene and to investigate its antiviral activity against canine parvovirus in Madin-Darby canine kidney cells (MDCK). [Methods] The cIFN-gamma gene was inserted into adenovirus shuttle plasmid to construct pShuttle3-cIFN-gamma expression vector, from which the cIFN-gamma expression cassette was transferred into the adenovirus genomic plasmid pAdeno-X by specific restriction sites to generate recombinant adenovirus genomic plasmid pAd-cIFN-gamma. The pAd-cIFN-gamma plasmid was linearized by digestion and transfected into human embryonic kidney (HEK) 293T cells to generate the replication-defective cIFN-gamma recombinant adenovirus (Ad-cIFN-gamma). To analyze its anti-canine parvovirus activity, the MDCK cells were pre-infected by Ad-cIFN-gamma recombinant adenovirus, and then infected by canine parvovirus. The antiviral activity of the Ad-cIFN-gamma recombinant adenovirus against parvovirus was analyzed. The recombinant adenovirus containing cIFN-gamma gene was constructed by the ligation method. The recombinant adenovirus could mediates recombinant cIFN-gamma secretory expression in MDCK cells. The Ad-cIFN-gamma recombinant adenovirus could significantly inhibit canine parvovirus replication in MDCK cells pre-infected with the recombinant adenovirus. These results indicate that the Ad-cIFN-gamma recombinant adenovirus has the potent antiviral activity against canine parvovirus. The Ad-cIFN-gamma recombinant adenovirus was successfully constructed by the ligation method and possessed a powerful antiviral activity against canine parvovirus.

  18. Irf3 polymorphism alters induction of interferon beta in response to Listeria monocytogenes infection.

    Directory of Open Access Journals (Sweden)

    Oleg Garifulin

    2007-09-01

    Full Text Available Genetic makeup of the host plays a significant role in the course and outcome of infection. Inbred strains of mice display a wide range of sensitivities to Listeria monocytogenes infection and thus serve as a good model for analysis of the effect of genetic polymorphism. The outcome of L. monocytogenes infection in mice is influenced by the ability of this bacterium to induce expression of interferon beta mRNA, encoded in mouse by the Ifnb1 (interferon beta 1, fibroblast gene. Mouse strains that lack components of the IFN beta signaling pathway are substantially more resistant to infection. We found that macrophages from the ByJ substrain of the common C57BL/6 inbred strain of mice are impaired in their ability to induce Ifnb1 expression in response to bacterial and viral infections. We mapped the locus that controls differential expression of Ifnb1 to a region on Chromosome 7 that includes interferon regulatory factor 3 (Irf3, which encodes a transcription factor responsible for early induction of Ifnb1 expression. In C57BL/6ByJ mice, Irf3 mRNA was inefficiently spliced, with a significant proportion of the transcripts retaining intron 5. Analysis of the Irf3 locus identified a single base-pair polymorphism and revealed that intron 5 of Irf3 is spliced by the atypical U12-type spliceosome. We found that the polymorphism disrupts a U12-type branchpoint and has a profound effect on the efficiency of splicing of Irf3. We demonstrate that a naturally occurring change in the splicing control element has a dramatic effect on the resistance to L. monocytogenes infection. Thus, the C57BL/6ByJ mouse strain serves as an example of how a mammalian host can counter bacterial virulence strategies by introducing subtle alteration of noncoding sequences.

  19. Effect of statins on clinical and molecular responses to intramuscular interferon beta-1a.

    Science.gov (United States)

    Rudick, R A; Pace, A; Rani, M R S; Hyde, R; Panzara, M; Appachi, S; Shrock, J; Maurer, S L; Calabresi, P A; Confavreux, C; Galetta, S L; Lublin, F D; Radue, E-W; Ransohoff, R M

    2009-06-09

    Findings from a small clinical study suggested that statins may counteract the therapeutic effects of interferon beta (IFNbeta) in patients with relapsing-remitting multiple sclerosis (RRMS). We conducted a post hoc analysis of data from the Safety and Efficacy of Natalizumab in Combination With IFNbeta-1a in Patients With Relapsing-Remitting Multiple Sclerosis (SENTINEL) study to determine the effects of statins on efficacy of IFNbeta. SENTINEL was a prospective trial of patients with RRMS treated with natalizumab (Tysabri, Biogen Idec, Inc., Cambridge, MA) plus IM IFNbeta-1a (Avonex, Biogen Idec, Inc.) 30 microg compared with placebo plus IM IFNbeta-1a 30 microg. Clinical and MRI outcomes in patients treated with IM IFNbeta-1a only (no-statins group, n = 542) were compared with those of patients taking IM IFNbeta-1a and statins at doses used to treat hyperlipidemia (statins group, n = 40). No significant differences were observed between treatment groups in adjusted annualized relapse rate (p = 0.937), disability progression (p = 0.438), number of gadolinium-enhancing lesions (p = 0.604), or number of new or enlarging T2-hyperintense lesions (p = 0.802) at 2 years. More patients in the statins group reported fatigue, extremity pain, muscle aches, and increases in hepatic transaminases compared with patients in the no-statins group. Statin treatment had no ex vivo or in vitro effect on induction of IFN-stimulated genes. Statin therapy does not appear to affect clinical effects of IM interferon beta-1a in patients with relapsing-remitting multiple sclerosis or the primary molecular response to interferon beta treatment.

  20. Interleukin-15 differentially enhances the expression of interferon-gamma and interleukin-4 in activated human (CD4(+))T lymphocytes

    NARCIS (Netherlands)

    Borger, P; Kauffman, HF; Postma, DS; Esselink, MT; Vellenga, E

    In this study interleukin (IL)-15 was examined for its ability to modulate the expression of interferon-gamma (IFN-gamma) and IL-4 in activated human T lymphocytes. The effect of IL-15 was compared with IL-2 and IL-7, cytokines all known to use the IL-2 receptor gamma(C) chain. The results

  1. Interferon gamma peptidomimetic targeted to hepatic stellate cells ameliorates acute and chronic liver fibrosis in vivo.

    Science.gov (United States)

    Bansal, Ruchi; Prakash, Jai; De Ruiter, Marieke; Poelstra, Klaas

    2014-04-10

    Hepatic stellate cells play a crucial role in the pathogenesis of hepatic fibrosis. Thus, pharmacological inhibition of pro-fibrotic activities of these cells might lead to an effective therapy for this disease. Among the potent anti-fibrotics, interferon gamma (IFNγ), a proinflammatory cytokine, is highly efficacious but it failed in clinical trials due to the poor efficacy and multiple adverse effects attributed to the ubiquitous IFNγ receptor (IFNγR) expression. To resolve these drawbacks, we chemically synthesized a chimeric molecule containing (a) IFNγ signaling peptide (IFNγ peptidomimetic, mimγ) that retains the agonistic activities of IFNγ but lacks an extracellular receptor recognition sequence for IFNγR; coupled via heterobifunctional PEG linker to (b) bicyclic platelet derived growth factor beta receptor (PDGFβR)-binding peptide (BiPPB) to induce internalization into the stellate cells that express PDGFβR. The synthesized targeted IFNγ peptidomimetic (mimγ-BiPPB) was extensively investigated for its anti-fibrotic and adverse effects in acute and chronic CCl4-induced liver fibrosis models in mice. Treatment with mimγ-BiPPB, after the onset of disease, markedly inhibited both early and established hepatic fibrosis as reflected by a reduced intrahepatic α-SMA, desmin and collagen-I mRNA expression and protein levels. While untargeted mimγ and BiPPB had no effect, and native IFNγ only induced a moderate reduction. Additionally, no off-target effects, e.g. systemic inflammation, were found with mimγ-BiPPB, which were substantially observed in mice treated with native IFNγ. The present study highlights the beneficial effects of a novel BiPPB mediated cell-specific targeting of IFNγ peptidomimetic to the disease-inducing cells and therefore represents a highly potential therapeutic approach to treat fibrotic diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Interferon

    CERN Multimedia

    De Somer,P

    1975-01-01

    Le Prof.Pierre de Somer est né en Belgique et a fait ses études de médecine à l'Université de Louvin où il a obtenu en 1942 son diplôme. En 1961 il a été nommé professeur ordinaire d'hygiène et de microbiologie à cette même Université et depuis 1967 il est recteur de l'Université catholique flamande de Louvin, président de la société belge de microbiologie et expert de l'O.M.S. Il nous parle de l'interferon et de ses perspectives dans le traitement de maladies virales avec présentation des clichées.

  3. Production and characterization of guinea pig recombinant gamma interferon and its effect on macrophage activation.

    Science.gov (United States)

    Jeevan, A; McFarland, C T; Yoshimura, T; Skwor, T; Cho, H; Lasco, T; McMurray, D N

    2006-01-01

    Gamma interferon (IFN-gamma) plays a critical role in the protective immune responses against mycobacteria. We previously cloned a cDNA coding for guinea pig IFN-gamma (gpIFN-gamma) and reported that BCG vaccination induced a significant increase in the IFN-gamma mRNA expression in guinea pig cells in response to living mycobacteria and that the virulent H37Rv strain of Mycobacterium tuberculosis stimulated less IFN-gamma mRNA than did the attenuated H37Ra strain. In this study, we successfully expressed and characterized recombinant gpIFN-gamma with a histidine tag at the N terminus (His-tagged rgpIFN-gamma) in Escherichia coli. rgpIFN-gamma was identified as an 18-kDa band in the insoluble fraction; therefore, the protein was purified under denaturing conditions and renatured. N-terminal amino acid sequencing of the recombinant protein yielded the sequence corresponding to the N terminus of His-tagged gpIFN-gamma. The recombinant protein upregulated major histocompatibility complex class II expression in peritoneal macrophages. The antiviral activity of rgpIFN-gamma was demonstrated with a guinea pig fibroblast cell line (104C1) infected with encephalomyocarditis virus. Interestingly, peritoneal macrophages treated with rgpIFN-gamma did not produce any nitric oxide but did produce hydrogen peroxide and suppressed the intracellular growth of mycobacteria. Furthermore, rgpIFN-gamma induced morphological alterations in cultured macrophages. Thus, biologically active rgpIFN-gamma has been successfully produced and characterized in our laboratory. The study of rgpIFN-gamma will further increase our understanding of the cellular and molecular responses induced by BCG vaccination in the guinea pig model of pulmonary tuberculosis.

  4. Enhancement by gamma-interferon of in vivo tumor radiolocalization by a monoclonal antibody against HLA-DR antigen

    International Nuclear Information System (INIS)

    Rowlinson, G.; Balkwill, F.; Snook, D.; Hooker, G.; Epenetos, A.A.

    1986-01-01

    Athymic nu/nu (nude) mice bearing s.c. human breast tumors were treated systemically with recombinant human gamma-interferon. These tumors were phenotypically negative for HLA-DR prior to therapy, but after 4 days of treatment, 80% of the cells expressed this antigen in vivo as assessed by immunoperoxidase (F. R. Balkwill et al., Eur. J. Cancer Clin. Oncol., in press, 1986). A radioiodine-labeled murine monoclonal antibody (TAL-1B5) against HLA-DR specifically localized to the tumors in recombinant human gamma-interferon-treated but not in control mice. An isotype-identical murine monoclonal antibody that did not react with control or recombinant human gamma-interferon-treated tumors did not show any specific localization. These results demonstrate that specific localization to tumors of radio-labeled monoclonal antibodies to HLA-DR can be facilitated by systemic therapy with gamma-interferon

  5. Gamma Interferon-Induced Guanylate Binding Protein 1 Is a Novel Actin Cytoskeleton Remodeling Factor

    OpenAIRE

    Ostler, Nicole; Britzen-Laurent, Nathalie; Liebl, Andrea; Naschberger, Elisabeth; Lochnit, Günter; Ostler, Markus; Forster, Florian; Kunzelmann, Peter; Ince, Semra; Supper, Verena; Praefcke, Gerrit J. K.; Schubert, Dirk W.; Stockinger, Hannes; Herrmann, Christian; Stürzl, Michael

    2014-01-01

    Gamma interferon (IFN-γ) regulates immune defenses against viruses, intracellular pathogens, and tumors by modulating cell proliferation, migration, invasion, and vesicle trafficking processes. The large GTPase guanylate binding protein 1 (GBP-1) is among the cellular proteins that is the most abundantly induced by IFN-γ and mediates its cell biologic effects. As yet, the molecular mechanisms of action of GBP-1 remain unknown. Applying an interaction proteomics approach, we identified actin a...

  6. Crystal structure of human interferon-gamma receptor 2 reveals the structural basis for receptor specificity

    Czech Academy of Sciences Publication Activity Database

    Mikulecký, Pavel; Zahradník, Jiří; Kolenko, Petr; Černý, Jiří; Charnavets, Tatsiana; Kolářová, Lucie; Nečasová, Iva; Pham, Phuong Ngoc; Schneider, Bohdan

    2016-01-01

    Roč. 72, č. 9 (2016), s. 1017-1025 ISSN 2059-7983 R&D Projects: GA ČR(CZ) GA16-20507S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : interferon-gamma receptor 2 * fibronectin type III domain * class 2 cytokine receptors Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.114, year: 2016

  7. INTERFERON BETA IN TREATMENT OF DISSEMINATED SCLEROSIS IN ADOLESCENTS — INFLUENCE ON NEUROPSYCHOLOGICAL STATUS AND PAROXYSMAL STATES

    Directory of Open Access Journals (Sweden)

    A.N. Platonova

    2010-01-01

    Full Text Available Disseminated sclerosis is chronic progressive disease of central nervous system, which is characterized by demyelination, degeneration of nerve fibers and polymorphous clinical symptoms. According to literature data, 2–10% of patients have onset of a disease in childhood and adolescence. Frequent clinical symptoms of disseminated sclerosis, especially in adolescents, are paroxysmal states and neuropsychological disorders. Drugs containing interferon beta which are used for immunomodulating treatment, can increase the rate of paroxysmal neuropsychological disorders in patients with disseminated sclerosis. Present study with participation of 78 adolescents analyzed frequency and spectrum of neuropsychological disorders and paroxysmal states in patients 12–17 years old and relation of revealed disorders with a treatment with interferon beta.Key words: adolescents, disseminated sclerosis, interferon beta, treatment, depression, paroxysmal states, anxiety, neuropsychological testing.(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(4:34-39

  8. Evaluation of Interferon-gamma Application for Recognition of Patients Afflicted by Non-healing Cutaneous Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Mohammad Moafi

    2017-06-01

    Full Text Available Introduction:Different studies undertaken in the animal modeling show that Interferon-gamma deficiency impairs healing process of Leishmania infection. It seems that the level of Interferon-gamma production could also affect the healing duration of Leishmania lesion in humans. The current study aims to investigate the possibility of Interferon-gamma application for recognition of cases afflicted by non-healing Leishmaniasis. Materials and methods: Peripheral blood mononuclear cells (PBMCs of 32 patients, who were afflicted by healing or non-healing Leishmaniasis, were isolated and the levels of interferon-gamma were determined, using ELISA method. Afterwards, the cut-off point of interferon-gamma to identify patients afflicted by non-healing Leishmaniasis was calculated through ROC-Curve analysis. Furthermore, Leishmanin Skin Test (LST was performed for every patient. Results: Levels of Interferon-gamma produced by PBMCs stimulated with Soluble Leishmania Antigen (SLA or Phytohemaglotinine were significantly higher in healing patients, compared with non-healing individuals (p

  9. Interferon gamma increases survival in urine experimental cryptococcosis El Interferon gamma incrementa la sobrevida de un modelo experimental murino de criptococosis

    Directory of Open Access Journals (Sweden)

    Amadeo J. Bava

    1995-10-01

    Full Text Available Systemic disease by Cryptococcus neoformans (C. neoformans is a common opportunistic infection in immunodeficient patients. Cellular immunity seems to be the most important determinant of resistance. The aim of this study was to assess the effect of recombinant rat interferon gamma (IFN-gamma in murine cryptococcosis (Balb/c mice infected by IP route with the Rivas strain of C. neoformans, evaluating survival time, macroscopic and microscopic examination of the organs, and massive seeding of brain homogenate. IFN-gamma treatment, at a daily dose of 10,000 IU, did not modify significantly these variables when mice were challenged with a high inoculum (10(7 yeasts and treatment was delayed to 5 days after infection (median survival 21 days in control mice vs. 23 days in IFN-treated. Another set of experiments suggested that IFN-gamma treatment, at a dose of 10,000 IU/day, begun at the moment of infection could be useful (it prolonged survival from 20 to 28 days, although the difference did not achieve statistical signification. When used simultaneously with infection by 3.5 x 10(5 yeasts, IFN-gamma at 10,000 IU/day for 15 days significantly prolonged survival of mice (p = 0.004. These results suggest that, depending on the experimental conditions, IFN-gamma can improve survival of mice infected with a lethal dose of C. neoformans.Se evaluó la efectividad del interferon-gamma (IFN-gamma recombinante de rata en un modelo experimental de criptococosis desarollado en ratones Balb/C inoculados por vía intraperitoneal con la cepa Rivas de Cryptococcus neoformans (C. neoformans. Se tuvieron en cuenta el tiempo de sobrevida de los animales, el aspecto macroscópico de los órganos en la autopsia, la presencia de levaduras capsuladas en los tejidos y la siembra masiva de un homogenato de cerebro. El tratamiento con IFN-gamma, en dosis diarias de 10.000 UI, no modificó estos parámetros cuando la dosis infectante fue de 10(7 levaduras y el tratamiento se

  10. Interpretation of the gamma interferon test for diagnosis of subclinical paratuberculosis in cattle

    DEFF Research Database (Denmark)

    Jungersen, Gregers; Huda, A.; Hansen, J.J.

    2002-01-01

    A group of 252 cattle without clinical signs of paratuberculosis (paraTB) in 10 herds infected with paraTB and a group of 117 cattle in 5 herds without paraTB were selected. Whole-blood samples were stimulated with bovine, avian, and johnin purified protein derivative (PPD) and examined for gamma...... interferon (IFN-gamma) release. For diagnosis of paraTB, satisfactory estimated specificities (95 to 99%) could be obtained by johnin PPD stimulation irrespective of interpretation relative to bovine PPD or no-antigen stimulation alone, but numbers of test positives in the infected herds varied from 64...

  11. Review of interferon beta-1b in the treatment of early and relapsing multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Damiano Paolicelli

    2009-07-01

    Full Text Available Damiano Paolicelli, Vita Direnzo, Maria TrojanoDepartment of Neurological and Psychiatric Sciences, University of Bari, Bari, ItalyAbstract: Multiple sclerosis (MS is the most common autoimmune illness of the central nervous system. For many years the inflammatory manifestations of MS were treated using only corticosteroids. Since the 1990s the results of several clinical trials with immunomodulatory agents have changed the therapeutic approach to this disease. Interferon beta (IFNβ-1b represents the pioneer of those therapies. There is growing evidence from clinical trials on relapsing-remitting MS and clinically isolated syndromes suggestive of MS that IFNβ-1b reduces the frequency and severity of relapses and the development of new and active brain lesions as assessed by magnetic resonance imaging. Long-term data suggest a persistent efficacy of IFNβ-1b on disease activity and a positive effect in slowing disability worsening. Furthermore a reduction of relapse rate and a slight positive effect on the progression were demonstrated when IFNβ-1b was administered to still-active secondary progressive MS. IFNβ-1b therapy is well tolerated and relatively free of long-term side effects. In spite of the emergence of new agents for the treatment of MS, IFNβ-1b still remains a first-line therapy with a fundamental role in all stages of the disease.Keywords: interferon beta-1b, relapsing-remitting multiple sclerosis, clinically isolated syndromes, efficacy, safety, neutralizing antibodies

  12. Effectiveness of interferon-[beta], ACNU, and radiation therapy in pediatric patients with brainstem glioma

    Energy Technology Data Exchange (ETDEWEB)

    Wakabayashi, Toshihiko; Yoshida, Jun; Mizuno, Masaaki; Sugita, Kenichiro [Nagoya Univ. (Japan). Faculty of Medicine; Kito, Akira

    1992-12-01

    Sixteen pediatric patients with brainstem glioma were treated with a combination of interferon-[beta], 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl -3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), and radiation therapy (IAR therapy). All patients received 1-1.5 million IU/day of interferon-[beta] intravenously for 1 week of each 6-week cycle. In addition, ACNU (2-3 mg/kg) was given on the 2nd day of each cycle. Conventional focal irradiation (1.5-2 Gy/day for 5 days to a total dosage of 40-60 Gy) was administered beginning on day 3. Patients underwent at least two 6-week cycles. Adverse effects included nausea, vomiting, and myelosuppression, but were mild and transient. Response to treatment was evaluated by the reduction in tumor size measured on postcontrast computed tomographic scans and magnetic resonance images. Responses occurred in 10 of 11 patients with the intrinsic type of brainstem glioma, including three complete and seven partial responses. Two of the five patients with exophytic type gliomas partially responded. The median survival was 15.7 months, a remarkable improvement over the natural course of this disease. These results indicate that IAR therapy is a useful primary treatment for pediatric patients with brainstem gliomas. (author).

  13. The immunomodulatory effects of interferon-gamma on mature B-lymphocyte responses.

    Science.gov (United States)

    Jurado, A; Carballido, J; Griffel, H; Hochkeppel, H K; Wetzel, G D

    1989-06-15

    Interferon-gamma (IFN-gamma) exerts a broad spectrum of activities which affect the responses of mature B-cells. It strongly inhibits B-cell activation, acts as a B-cell growth factor (BCGF), and also induces final differentiation to immunoglobulin (Ig) production. IFN-gamma is deeply involved in the differential control of isotype expression, as it enhances IgG2a production and suppresses both IgG1 and IgE production. Although it is now possible to draw a general scheme of the effects of IFN-gamma on B-cells, a number of paradoxical results still exist in the field. In this manuscript, different experimental systems are analyzed in an attempt to explain these apparent paradoxes.

  14. Whole blood interferon-gamma assay for baseline tuberculosis screening among Japanese healthcare students.

    Directory of Open Access Journals (Sweden)

    Katsuyuki Hotta

    Full Text Available BACKGROUND: The whole blood interferon-gamma assay (QuantiFERON-TB-2G; QFT has not been fully evaluated as a baseline tuberculosis screening test in Japanese healthcare students commencing clinical contact. The aim of this study was to compare the results from the QFT with those from the tuberculin skin test (TST in a population deemed to be at a low risk for infection with Mycobacterium tuberculosis. METHODOLOGY/PRINCIPAL FINDINGS: Healthcare students recruited at Okayama University received both the TST and the QFT to assess the level of agreement between these two tests. The interleukin-10 levels before and after exposure to M tuberculosis-specific antigens (early-secreted antigenic target 6-kDa protein [ESAT-6] and culture filtrate protein 10 [CFP-10] were also measured. Of the 536 healthcare students, most of whom had been vaccinated with bacillus-Calmette-Guérin (BCG, 207 (56% were enrolled in this study. The agreement between the QFT and the TST results was poor, with positive result rates of 1.4% vs. 27.5%, respectively. A multivariate analysis also revealed that the induration diameter of the TST was not affected by the interferon-gamma concentration after exposure to either of the antigens but was influenced by the number of BCG needle scars (p = 0.046. The whole blood interleukin-10 assay revealed that after antigen exposure, the median increases in interleukin-10 concentration was higher in the subgroup with the small increase in interferon-gamma concentration than in the subgroup with the large increase in interferon-gamma concentration (0.3 vs. 0 pg/mL; p = 0.004. CONCLUSIONS/SIGNIFICANCE: As a baseline screening test for low-risk Japanese healthcare students at their course entry, QFT yielded quite discordant results, compared with the TST, probably because of the low specificity of the TST results in the BCG-vaccinated population. We also found, for the first time, that the change in the interleukin-10 level after exposure to

  15. Adjuvant interferon gamma in patients with drug – resistant pulmonary tuberculosis: a pilot study

    Directory of Open Access Journals (Sweden)

    Carbonell Dalia

    2004-10-01

    Full Text Available Abstract Background Tuberculosis (TB is increasing in the world and drug-resistant (DR disease beckons new treatments. Methods To evaluate the action of interferon (IFN gamma as immunoadjuvant to chemotherapy on pulmonary DR-TB patients, a pilot, open label clinical trial was carried out in the Cuban reference ward for the management of this disease. The eight subjects existing in the country at the moment received, as in-patients, 1 × 106 IU of recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to the indicated chemotherapy, according to their antibiograms and WHO guidelines. Sputum samples collection for direct smear observation and culture as well as routine clinical and thorax radiography assessments were done monthly. Results Sputum smears and cultures became negative for acid-fast-bacilli before three months of treatment in all patients. Lesion size was reduced at the end of 6 months treatment; the lesions disappeared in one case. Clinical improvement was also evident; body mass index increased in general. Interferon gamma was well tolerated. Few adverse events were registered, mostly mild; fever and arthralgias prevailed. Conclusions These data suggest that IFN gamma is useful and well tolerated as adjunctive therapy in patients with DR-TB. Further controlled clinical trials are encouraged.

  16. Some biological properties of the human amniotic membrane interferon

    Directory of Open Access Journals (Sweden)

    P. C. P. Ferreira

    1992-03-01

    Full Text Available Human amniotic interferon was investigated to define the species specificity of its antiviral action and compare its anti-cellular and NK cell stimulating activities with those of other human interferons. The antiviral effect was titrated in bovine (RV-IAL and monkey (VERO cells. Amniotic interferon exhibited, in bovine cells, 5% of the activity seen in monkey cells, while alpha interferon displayed 200%. No effect was detected with either beta or gamma interferon in bovine cells. Daudi cells were exposed to different concentrations of various interferons and the cell numbers were determined. The anticellular effect of the amniotic interferon reached its peak on the third day of incubation. Results suggested a higher activity for alpha and gamma interferons and a lower activity for beta when compared to amniotic interferon. Using total mononuclear cells as effector cells and K 562 as target cell in a 51Cr release assay, it was demonstrated that low concentrations of amniotic interferon consistently stimulated NK cell activity in cells derived from several donors, the results indicating a higher level of activity with this interferon than with alpha and beta interferons.

  17. beta. and. gamma. -comparative dose estimates on Enewetak Atoll

    Energy Technology Data Exchange (ETDEWEB)

    Crase, K.W.; Gudiksen, P.H.; Robison, W.L. (California Univ., Livermore (USA). Lawrence Livermore National Lab.)

    1982-05-01

    Enewetak Atoll in the Pacific is used for atmospheric testing of U.S. nuclear weapons. Beta dose and ..gamma..-ray exposure measurements were made on two islands of the Enewetak Atoll during July-August 1976 to determine the ..beta.. and low energy ..gamma..-contribution to the total external radiation doses to the returning Marshallese. Measurements were made at numerous locations with thermoluminescent dosimeters (TLD), pressurized ionization chambers, portable NaI detectors, and thin-window pancake GM probes. Results of the TLD measurements with and without a ..beta..-attenuator indicate that approx. 29% of the total dose rate at 1 m in air is due to ..beta..- or low energy ..gamma..-contribution. The contribution at any particular site, however, is reduced by vegetation. Integral 30-yr external shallow dose estimates for future inhabitants were made and compared with external dose estimates of a previous large scale radiological survey. Integral 30-yr shallow external dose estimates are 25-50% higher than whole body estimates. Due to the low penetrating ability of the ..beta..'s or low energy ..gamma..'s, however, several remedial actions can be taken to reduce the shallow dose contribution to the total external dose.

  18. beta- and gamma-Comparative dose estimates on Eniwetok Atoll

    Energy Technology Data Exchange (ETDEWEB)

    Crase, K.W.; Gudiksen, P.H.; Robison, W.L.

    1982-05-01

    Eniwetok Atoll is one of the Pacific atolls used for atmospheric testing of U.S. nuclear weapons. Beta dose and gamma-ray exposure measurements were made on two islands of the Eniwetok Atoll during July-August 1976 to determine the beta and low energy gamma-contribution to the total external radiation doses to the returning Marshallese. Measurements were made at numerous locations with thermoluminescent dosimeters (TLD), pressurized ionization chambers, portable NaI detectors, and thin-window pancake GM probes. Results of the TLD measurements with and without a beta-attenuator indicate that approx. 29% of the total dose rate at 1 m in air is due to beta- or low energy gamma-contribution. The contribution at any particular site, however, is somewhat dependent on ground cover, since a minimal amount of vegetation will reduce it significantly from that over bare soil, but thick stands of vegetation have little effect on any further reductions. Integral 30-yr external shallow dose estimates for future inhabitants were made and compared with external dose estimates of a previous large scale radiological survey (En73). Integral 30-yr shallow external dose estimates are 25-50% higher than whole body estimates. Due to the low penetrating ability of the beta's or low energy gamma's, however, several remedial actions can be taken to reduce the shallow dose contribution to the total external dose.

  19. Determination of beta and gamma radioactivity on the coal

    International Nuclear Information System (INIS)

    Suhardi; Mulyono; Sutanto WW; Rosidi

    2013-01-01

    Radioactivity in coal, botton ash and fly ash. This determination was carried out to know each the radioactivity of β gross, γ gross on the coal, botton ash and fly ash, which accommodation of environment data the present in PLTU Paiton Probolinggo. Samples taken preparation and analysis based on the procedures of environmental radioactivity analysis. The radioactivity on the PLTU Paiton Probolinggo detected by beta gross Spectrometer with Geiger Muller (GM) and gamma Spectrometer with Ge(Li) detector. The result indicates that radioactivity concentration of beta and gamma gross are (95,57-308,26) Bq/kg and (1,374 - 31,677) Bq/kg respectively. (author)

  20. Nitric oxide selectively decreases interferon-gamma expression by activated human T lymphocytes via a cGMP-independent mechanism

    NARCIS (Netherlands)

    Roozendaal, R; Vellenga, E; Postma, DS; De Monchy, JGR; Kauffman, HF

    1999-01-01

    The role of exogenous nitric oxide (NO) on the expression of interleukin (IL)-2, IL-4, IL-5 and interferon-gamma (IFN-gamma) by freshly isolated human T lymphocytes was investigated. The presence of NO, generated from any of the NO-donor compounds, S-nitroso-N-acetyl-D,L-penicillamine (NAP),

  1. The structure of the human interferon alpha/beta receptor gene.

    Science.gov (United States)

    Lutfalla, G; Gardiner, K; Proudhon, D; Vielh, E; Uzé, G

    1992-02-05

    Using the cDNA coding for the human interferon alpha/beta receptor (IFNAR), the IFNAR gene has been physically mapped relative to the other loci of the chromosome 21q22.1 region. 32,906 base pairs covering the IFNAR gene have been cloned and sequenced. Primer extension and solution hybridization-ribonuclease protection have been used to determine that the transcription of the gene is initiated in a broad region of 20 base pairs. Some aspects of the polymorphism of the gene, including noncoding sequences, have been analyzed; some are allelic differences in the coding sequence that induce amino acid variations in the resulting protein. The exon structure of the IFNAR gene and of that of the available genes for the receptors of the cytokine/growth hormone/prolactin/interferon receptor family have been compared with the predictions for the secondary structure of those receptors. From this analysis, we postulate a common origin and propose an hypothesis for the divergence from the immunoglobulin superfamily.

  2. Occurrence of Psoriatic Arthritis during Interferon Beta 1a Treatment for Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Éric Toussirot

    2014-01-01

    Full Text Available Interferon beta (IFN-β is the first line therapy of relapsing-remitting multiple sclerosis. IFN-β is a cytokine that can contribute to the development of systemic autoimmune disease including psoriasis. The development or the exacerbation of psoriasis during IFN-β treatment has been previously observed. We report the occurrence of arthritis and dactylitis in a multiple sclerosis patient with preexisting psoriasis diagnosed as a psoriatic arthritis. The IL-23/Th17 pathway is involved in psoriasis and psoriatic arthritis and it has been suggested that IFN-β therapy in patients with Th17-mediated disease may be detrimental. Together with previous similar reports, our case suggests that IFN-β should certainly be used with caution in patients with concomitant systemic autoimmune disease with IL-23/Th17 involvement.

  3. Y-formalism and curved {beta}-{gamma} systems

    Energy Technology Data Exchange (ETDEWEB)

    Grassi, Pietro Antonio [DISTA, Universita del Piemonte Orientale, via Bellini 25/g, 15100 Alessandria (Italy); INFN - Sezione di Torino (Italy)], E-mail: antonio.pietro.grassi@cern.ch; Oda, Ichiro [Department of Physics, Faculty of Science, University of the Ryukyus, Nishihara, Okinawa 903-0213 (Japan); Tonin, Mario [Dipartimento di Fisica, Universita degli Studi di Padova, INFN, Sezionedi Padova, Via F. Marzolo 8, 35131 Padova (Italy)

    2009-01-01

    We adopt the Y-formalism to study {beta}-{gamma} systems on hypersurfaces. We compute the operator product expansions of gauge-invariant currents and we discuss some applications of the Y-formalism to model on Calabi-Yau spaces.

  4. Evaluation of beta-decay III. The complex gamma function

    International Nuclear Information System (INIS)

    Wilkinson, D.H.

    1993-05-01

    Two real, analytical, approximations for the square of the modulus of the complex gamma function as it appears in F(Z, W), the Fermi function for beta-decay, are evaluated; an accuracy bettering 10 -4 % can easily be achieved for all electron energies throughout the periodic table. (author). 3 refs., 1 tab., 7 figs

  5. Vaccinia virus recombinants expressing chimeric proteins of human immunodeficiency virus and gamma interferon are attenuated for nude mice.

    OpenAIRE

    Giavedoni, L D; Jones, L; Gardner, M B; Gibson, H L; Ng, C T; Barr, P J; Yilma, T

    1992-01-01

    We have developed a method for attenuating vaccinia virus recombinants by expressing a fusion protein of a lymphokine and an immunogen. Chimeric genes were constructed that coded for gamma interferon (IFN-gamma) and structural proteins of the human immunodeficiency virus type 1 (HIV-1). In this study, we describe the biological and immunological properties of vaccinia virus recombinants expressing chimeric genes of murine or human IFN-gamma with glycoprotein gp120, gag, and a fragment of gp41...

  6. Top-Down Beta Enhances Bottom-Up Gamma.

    Science.gov (United States)

    Richter, Craig G; Thompson, William H; Bosman, Conrado A; Fries, Pascal

    2017-07-12

    Several recent studies have demonstrated that the bottom-up signaling of a visual stimulus is subserved by interareal gamma-band synchronization, whereas top-down influences are mediated by alpha-beta band synchronization. These processes may implement top-down control of stimulus processing if top-down and bottom-up mediating rhythms are coupled via cross-frequency interaction. To test this possibility, we investigated Granger-causal influences among awake macaque primary visual area V1, higher visual area V4, and parietal control area 7a during attentional task performance. Top-down 7a-to-V1 beta-band influences enhanced visually driven V1-to-V4 gamma-band influences. This enhancement was spatially specific and largest when beta-band activity preceded gamma-band activity by ∼0.1 s, suggesting a causal effect of top-down processes on bottom-up processes. We propose that this cross-frequency interaction mechanistically subserves the attentional control of stimulus selection. SIGNIFICANCE STATEMENT Contemporary research indicates that the alpha-beta frequency band underlies top-down control, whereas the gamma-band mediates bottom-up stimulus processing. This arrangement inspires an attractive hypothesis, which posits that top-down beta-band influences directly modulate bottom-up gamma band influences via cross-frequency interaction. We evaluate this hypothesis determining that beta-band top-down influences from parietal area 7a to visual area V1 are correlated with bottom-up gamma frequency influences from V1 to area V4, in a spatially specific manner, and that this correlation is maximal when top-down activity precedes bottom-up activity. These results show that for top-down processes such as spatial attention, elevated top-down beta-band influences directly enhance feedforward stimulus-induced gamma-band processing, leading to enhancement of the selected stimulus. Copyright © 2017 Richter, Thompson et al.

  7. Interferon beta and vitamin D synergize to induce immunoregulatory receptors on peripheral blood monocytes of multiple sclerosis patients.

    Directory of Open Access Journals (Sweden)

    Anne Waschbisch

    Full Text Available Immunoglobulin-like transcript (ILT 3 and 4 are inhibitory receptors that modulate immune responses. Their expression has been reported to be affected by interferon, offering a possible mechanism by which this cytokine exerts its therapeutic effect in multiple sclerosis, a condition thought to involve excessive immune activity. To investigate this possibility, we measured expression of ILT3 and ILT4 on immune cells from multiple sclerosis patients, and in post-mortem brain tissue. We also studied the ability of interferon beta, alone or in combination with vitamin D, to induce upregulation of these receptors in vitro, and compared expression levels between interferon-treated and untreated multiple sclerosis patients. In vitro interferon beta treatment led to a robust upregulation of ILT3 and ILT4 on monocytes, and dihydroxyvitamin D3 increased expression of ILT3 but not ILT4. ILT3 was abundant in demyelinating lesions in postmortem brain, and expression on monocytes in the cerebrospinal fluid was higher than in peripheral blood, suggesting that the central nervous system milieu induces ILT3, or that ILT3 positive monocytes preferentially enter the brain. Our data are consistent with involvement of ILT3 and ILT4 in the modulation of immune responsiveness in multiple sclerosis by both interferon and vitamin D.

  8. Interferon-gamma in progression to chronic demyelination and neurological deficit following acute EAE

    DEFF Research Database (Denmark)

    Renno, T; Taupin, V; Bourbonnière, L

    1998-01-01

    The cytokine interferon-gamma (IFNgamma) is implicated in the induction of acute CNS inflammation, but it is less clear what role if any IFNgamma plays in progression to chronic demyelination and neurological deficit. To address this issue, we have expressed IFNgamma in myelinating oligodendrocytes....... In contrast to control mice, which remit from EAE with resolution of glial reactivity and leukocytic infiltration, transgenics showed chronic neurological deficits. While activated microglia/macrophages persisted in demyelinating lesions for over 100 days, CD4(+) T lymphocytes were no longer present in CNS...

  9. Development of an aptamer beacon for detection of interferon-gamma.

    Science.gov (United States)

    Tuleuova, Nazgul; Jones, Caroline N; Yan, Jun; Ramanculov, Erlan; Yokobayashi, Yohei; Revzin, Alexander

    2010-03-01

    Traditional antibody-based affinity sensing strategies employ multiple reagents and washing steps and are unsuitable for real-time detection of analyte binding. Aptamers, on the other hand, may be designed to monitor binding events directly, in real-time, without the need for secondary labels. The goal of the present study was to design an aptamer beacon for fluorescence resonance energy transfer (FRET)-based detection of interferon-gamma (IFN-gamma)--an important inflammatory cytokine. Variants of DNA aptamer modified with biotin moieties and spacers were immobilized on avidin-coated surfaces and characterized by surface plasmon resonance (SPR). The SPR studies showed that immobilization of aptamer via the 3' end resulted in the best binding IFN-gamma (K(d) = 3.44 nM). This optimal aptamer variant was then used to construct a beacon by hybridizing fluorophore-labeled aptamer with an antisense oligonucleotide strand carrying a quencher. SPR studies revealed that IFN-gamma binding with an aptamer beacon occurred within 15 min of analyte introduction--suggesting dynamic replacement of the quencher-complementary strand by IFN-gamma molecules. To further highlight biosensing applications, aptamer beacon molecules were immobilized inside microfluidic channels and challenged with varying concentration of analyte. Fluorescence microscopy revealed low fluorescence in the absence of analyte and high fluorescence after introduction of IFN-gamma. Importantly, unlike traditional antibody-based immunoassays, the signal was observed directly upon binding of analyte without the need for multiple washing steps. The surface immobilized aptamer beacon had a linear range from 5 to 100 nM and a lower limit of detection of 5 nM IFN-gamma. In conclusion, we designed a FRET-based aptamer beacon for monitoring of an inflammatory cytokine-IFN-gamma. In the future, this biosensing strategy will be employed to monitor dynamics of cytokine production by the immune cells.

  10. Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study.

    Science.gov (United States)

    Kalincik, Tomas; Brown, J William L; Robertson, Neil; Willis, Mark; Scolding, Neil; Rice, Claire M; Wilkins, Alastair; Pearson, Owen; Ziemssen, Tjalf; Hutchinson, Michael; McGuigan, Christopher; Jokubaitis, Vilija; Spelman, Tim; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Prat, Alexandre; Girard, Marc; Duquette, Pierre; Grammond, Pierre; Alroughani, Raed; Pucci, Eugenio; Sola, Patrizia; Hupperts, Raymond; Lechner-Scott, Jeannette; Terzi, Murat; Van Pesch, Vincent; Rozsa, Csilla; Grand'Maison, François; Boz, Cavit; Granella, Franco; Slee, Mark; Spitaleri, Daniele; Olascoaga, Javier; Bergamaschi, Roberto; Verheul, Freek; Vucic, Steve; McCombe, Pamela; Hodgkinson, Suzanne; Sanchez-Menoyo, Jose Luis; Ampapa, Radek; Simo, Magdolna; Csepany, Tunde; Ramo, Cristina; Cristiano, Edgardo; Barnett, Michael; Butzkueven, Helmut; Coles, Alasdair

    2017-04-01

    Alemtuzumab, an anti-CD52 antibody, is proven to be more efficacious than interferon beta-1a in the treatment of relapsing-remitting multiple sclerosis, but its efficacy relative to more potent immunotherapies is unknown. We compared the effectiveness of alemtuzumab with natalizumab, fingolimod, and interferon beta in patients with relapsing-remitting multiple sclerosis treated for up to 5 years. In this international cohort study, we used data from propensity-matched patients with relapsing-remitting multiple sclerosis from the MSBase and six other cohorts. Longitudinal clinical data were obtained from 71 MSBase centres in 21 countries and from six non-MSBase centres in the UK and Germany between Nov 1, 2015, and June 30, 2016. Key inclusion criteria were a diagnosis of definite relapsing-remitting multiple sclerosis, exposure to one of the study therapies (alemtuzumab, interferon beta, fingolimod, or natalizumab), age 65 years or younger, Expanded Disability Status Scale (EDSS) score 6·5 or lower, and no more than 10 years since the first multiple sclerosis symptom. The primary endpoint was annualised relapse rate. The secondary endpoints were cumulative hazards of relapses, disability accumulation, and disability improvement events. We compared relapse rates with negative binomial models, and estimated cumulative hazards with conditional proportional hazards models. Patients were treated between Aug 1, 1994, and June 30, 2016. The cohorts consisted of 189 patients given alemtuzumab, 2155 patients given interferon beta, 828 patients given fingolimod, and 1160 patients given natalizumab. Alemtuzumab was associated with a lower annualised relapse rate than interferon beta (0·19 [95% CI 0·14-0·23] vs 0·53 [0·46-0·61], pmultiple sclerosis. Alemtuzumab seems superior to fingolimod and interferon beta in mitigating relapse activity. Natalizumab seems superior to alemtuzumab in enabling recovery from disability. Both natalizumab and alemtuzumab seem highly

  11. Interferon-gamma sensitizes colonic epithelial cell lines to physiological and therapeutic inducers of colonocyte apoptosis.

    LENUS (Irish Health Repository)

    O'Connell, J

    2012-02-03

    Homeostasis in the colonic epithelium is achieved by a continuous cycle of proliferation and apoptosis, in which imbalances are associated with disease. Inflammatory bowel disease (IBD) and colon cancer are associated with either excessive or insufficient apoptosis of colonic epithelial cells, respectively. By using two colonic epithelial cell lines, HT29 and SW620, we investigated how the epithelial cell\\'s sensitivity to apoptosis was regulated by the proinflammatory cytokine interferon-gamma (IFN-gamma). We found that IFN-gamma sensitized HT29 cells, and to a lesser extent SW620, to diverse inducers of apoptosis of physiologic or therapeutic relevance to the colon. These apoptosis inducers included Fas (CD95\\/APO-1) ligand (FasL), short-chain fatty acids, and chemotherapeutic drugs. The extent of IFN-gamma-mediated apoptosis sensitization in these two cell lines correlated well with the degree of IFN-gamma-mediated upregulation of the proapoptotic protease caspase-1. Although IFN-gamma alone effectively sensitized HT29 cells to apoptosis, inclusion of the protein synthesis inhibitor cyclohexamide (CHX) during apoptotic challenge was necessary for maximal sensitization of SW620. The requirement of CHX to sensitize SW620 cells to apoptosis implies a need to inhibit translation of antiapoptotic proteins absent from HT29. In particular, the antiapoptotic protein Bcl-2 was strongly expressed in SW620 cells but absent from HT29. Our results indicate that IFN-gamma increases the sensitivity of colonic epithelial cells to diverse apoptotic stimuli in concert, via upregulation of caspase-1. Our findings implicate caspase-1 and Bcl-2 as important central points of control determining the general sensitivity of colonic epithelial cells to apoptosis.

  12. Human gamma interferon production by cytotoxic T lymphocytes sensitized during hepatitis A virus infection

    International Nuclear Information System (INIS)

    Maier, K.; Gabriel, P.; Koscielniak, E.; Stierhof, Y.D.; Wiedmann, K.H.; Flehmig, B.; Vallbracht, A.

    1988-01-01

    The production of interferon (IFN) during a chromium-51 release assay with hepatitis A virus (HAV)-infected fibroblasts and autologous peripheral blood lymphocytes from patients with acute HAV infection was studied to determine whether IFN plays a role in immunopathogenesis of hepatitis A infection in humans. Skin fibroblasts of eight patients after acute HAV infection and from two control persons without history of current of past HAV infection were infected with HAV. Peripheral blood lymphocytes were collected at different times after the onset of icterus and tested in a chromium-51 release assay against autologous HAV-infected skin fibroblasts for their cytolytic and IFN-producing activity. The IFN produced during the assay was characterized and found to have the properties of human gamma IFN. Cytotoxicity and gamma IFN release were virus specific. The cell types responsible for both functions were characterized and found to be in the HLA-dependent T8 + lymphocyte subset. Considering that gamma IFN has an antiviral effect on persistent HAV infection in vitro and that it probably accounts for stimulation of HLA class I antigen expression on hepatocytes, these experimental results presented here demonstrate that human gamma IFN produced by HAV-specific T cells may participate in pathogenesis of hepatitis A infection in humans

  13. Injectable interferon beta-1b for the treatment of relapsing forms of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Slobodan M Jankovic

    2010-03-01

    Full Text Available Slobodan M JankovicPharmacology Department, Medical Faculty, University of Kragujevac, Kragujevac, SerbiaAbstract: Multiple sclerosis (MS is chronic inflammatory and demyelinating disease with either a progressive (10%–15% or relapsing-remitting (85%–90% course. The pathological hallmarks of MS are lesions of both white and grey matter in the central nervous system. The onset of the disease is usually around 30 years of age. The patients experience an acute focal neurologic dysfunction which is not characteristic, followed by partial or complete recovery. Acute episodes of neurologic dysfunction with diverse signs and symptoms will then recur throughout the life of a patient, with periods of partial or complete remission and clinical stability in between. Currently, there are several therapeutic options for MS with disease-modifying properties. Immunomodulatory therapy with interferon beta-1b (IFN-β1b or -1a, glatiramer and natalizumab shows similar efficacy; in a resistant or intolerant patient, the most recently approved therapeutic option is mitoxantrone. IFN-β1b in patients with MS binds to specific receptors on surface of immune cells, changing the expression of several genes and leading to a decrease in quantity of cell-associated adhesion molecules, inhibition of major histocompatibility complex class II expression and reduction in inflammatory cells migration into the central nervous system. After 2 years of treatment, IFN-β1b reduces the risk of development of clinically defined MS from 45% (with placebo to 28% (with IFN-β1b. It also reduces relapses for 34% (1.31 exacerbations annually with placebo and 0.9 with higher dose of IFN-β1b and makes 31% more patients relapse-free. In secondary-progressive disease annual rate of progression is 3% lower with IFN-β1b. In recommended doses IFN-β1b causes the following frequent adverse effects: injection site reactions (redness, discoloration, inflammation, pain, necrosis and non

  14. Adjuvant interferon gamma in patients with pulmonary atypical Mycobacteriosis: A randomized, double-blind, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Sánchez-de la Osa Reinaldo B

    2008-02-01

    Full Text Available Abstract Background High antibiotic resistance is described in atypical Mycobacteriosis, mainly by Mycobacterium avium complex (MAC. Methods A randomized, double-blind, placebo-controlled clinical trial was carried out in two hospitals to evaluate the effect of interferon (IFN gamma as immunoadjuvant to chemotherapy on patients with atypical mycobacteria lung disease. Patients received placebo or 1 × 106 IU recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to daily oral azithromycin, ciprofloxacin, ethambutol and rifampin. Sputum samples collection for direct smear observation and culture as well as clinical and thorax radiography assessments were done during treatment and one year after. Cytokines and oxidative stress determinations were carried out in peripheral blood before and after treatment. Results Eighteen patients were included in the IFN group and 14 received placebo. Groups were homogeneous at entry; average age was 60 years, 75% men, 84% white; MAC infection prevailed (94%. At the end of treatment, 72% of patients treated with IFN gamma were evaluated as complete responders, but only 36% in the placebo group. The difference was maintained during follow-up. A more rapid complete response was obtained in the IFN group (5 months before, with a significantly earlier improvement in respiratory symptoms and pulmonary lesions reduction. Disease-related deaths were 35.7% of the patients in the placebo group and only 11.1% in the IFN group. Three patients in the IFN group normalized their globular sedimentation rate values. Although differences in bacteriology were not significant during the treatment period, some patients in the placebo group converted again to positive during follow-up. Significant increments in serum TGF-beta and advanced oxidation protein products were observed in the placebo group but not among IFN receiving patients. Treatments were well tolerated

  15. SAFETY OF INTERFERON BETA 1A FOR A SUBCUTANEOUS ADMINISTRATION IN CHILDREN AND ADOLESCENTS WITH DISSEMINATED SCLEROSIS

    Directory of Open Access Journals (Sweden)

    O.V. Bykova

    2008-01-01

    Full Text Available The onset of disseminated sclerosis occurs in childhood and juvenile age in 10% of patients. nevertheless, all immunomodulatory drugs for a treatment of this disease intended for adult population of patients, and there's an age limitation to the administration of these medications. There's only one interferon beta in group of «changing the clinical course of disseminated sclerosis medications», that was annotated to the administration in patients from 16 years. It's interferon betab1a (Rebif for subcutaneous administration in 22 ?g and 44 ?g dosage. This drug was well known as an effective and safe medication for a long term administration for a long time in adult neurological practice. But doctors have to use interferon betab1a «off label» yet in patients younger 16 years in Russia and in other countries, comparing risk of changing the regimen of age limitation and risk of deprivation of un derbaged patient of years of qualitative life.Key words: children, disseminated sclerosis, interferon beta 1a, treatment.

  16. INTERFERON BETA-1A TREATMENT IN HTLV-1-ASSOCIATED MYELOPATHY/TROPICAL SPASTIC PARAPARESIS: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Graça Maria de Castro Viana

    2014-09-01

    Full Text Available Here a young patient (< 21 years of age with a history of infective dermatitis is described. The patient was diagnosed with myelopathy associated with HTLV-1/tropical spastic paraparesis and treated with interferon beta-1a. The disease was clinically established as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP, and laboratory tests confirmed the presence of antibodies to HTLV-1 in the cerebrospinal fluid (CSF. Mumps, cytomegalovirus, Epstein-Barr virus, schistosomiasis, herpes virus 1 and 2, rubella, measles, varicella-zoster toxoplasmosis, hepatitis, HIV, and syphilis were excluded by serology. The patient was diagnosed with neurogenic bladder and presented with nocturia, urinary urgency, paresthesia of the lower left limb, a marked reduction of muscle strength in the lower limbs, and a slight reduction in upper limb strength. During the fourth week of treatment with interferon beta-1a, urinary urgency and paresthesia disappeared and clinical motor skills improved.

  17. Experimentation with a prototype incinerator for beta-gamma waste

    International Nuclear Information System (INIS)

    Farber, M.G.; Lewandowski, K.E.; Becker, G.W.

    1982-01-01

    A test facility for the incineration of suspect and low-level beta-gamma waste has been built and operated at the Savannah River Laboratory. The processing steps include waste feeding, incineration, ash residue packaging, and off-gas cleanup. Demonstration of the full-scale (180 kg/hr) facility with nonradioactive, simulated waste is currently in progress. At the present time, over nine metric tons of material including rubber, polyethylene, and cellulose have been incinerated during three burning campaigns. A comprehensive test program of solid and liquid waste incineration is being implemented. The data from the research program is providing the technical basis for a phase of testing with low-level beta-gamma waste generated at the Savannah River Plant

  18. PEGylated interferon beta-1a in the treatment of multiple sclerosis – an update

    Directory of Open Access Journals (Sweden)

    Reuss R

    2013-05-01

    Full Text Available Reinhard ReussDepartment of Neurology, BKH Bayreuth, Bayreuth, GermanyAbstract: Current standard immunomodulatory therapy with interferons (IFNs for relapsing–remitting multiple sclerosis (MS exhibits proven, but limited, efficacy and increased side effects due to the need of frequent application of the drug. Therefore, there is a need for more effective and tolerable drugs. Due to their small size, optimization of therapy with IFNs in MS by PEGylation is feasible. PEGylation of an IFN means that at least one molecule of polyethylene glycol (PEG is covalently added. This modification is a standard procedure to increase the stability, solubility, half-life, and efficacy of a drug, and is applied in several drugs and diseases. Currently, a therapy regimen applying PEG-IFN beta-1a in MS is being developed to achieve an optimized relationship between therapy-related side effects and pharmacokinetic/pharmacodynamic efficacy. Phase I studies demonstrated that subcutaneous PEG-IFN beta-1a at a dose of 125 µg every 2 or 4 weeks might be at least as efficient and safe as the current standard therapy with IFN beta-1a. A global Phase III clinical study is investigating the efficacy of PEG-IFN beta-1a in terms of reduction of the relapse rate in relapsing–remitting MS patients. The latest primary safety and efficacy analysis after 1 year has revealed a favorable risk–benefit profile with no significant difference between dosing regimens. Compared to placebo, the annualized relapse rate was reduced by about one-third and new or newly enlarging T2 brain lesions were reduced by about one-third when dosing every 4 weeks or by two-thirds when dosing every 2 weeks. This presents a significant effect of the dosing interval, favoring administration every 2 weeks. Chronic administration of PEGylated proteins mostly at toxic concentrations causes vacuolation of renal epithelium in animals, which – along with the issue of occurrence of anti-PEG antibodies

  19. Absence of MxA induction by interferon beta in patients with MS reflects complete loss of bioactivity

    DEFF Research Database (Denmark)

    Hesse, D.; Sellebjerg, F.; Sorensen, P.S.

    2009-01-01

    BACKGROUND: In patients with multiple sclerosis (MS), neutralizing antibodies (NAbs) appearing during treatment with interferon (IFN) beta reduce or in high concentrations abolish bioactivity and therapeutic efficacy. In vivo MxA induction by IFNbeta is used as a marker of biologic response....... Lack of MxA in vivo response in patients with multiple sclerosis with NAbs is a reliable marker of a completely blocked biologic response to IFNbeta, with no indication of residual bioactivity Udgivelsesdato: 2009/8/4...

  20. PC based alpha, beta and gamma counting system

    International Nuclear Information System (INIS)

    Bhattacharya, S.; Gopalakrishnan, K.R.; Bairi, B.R.

    1992-01-01

    In the field of radiation protection and safety a large number of samples have to be assayed for estimation of their radioactivity at various stages in nuclear fuel. A PC based alpha, beta and gamma counting system has been designed for the above application. The system is fully automatic and requires minimum of operator intervention. The main units in the system are detector and pulse processing electronics, sample changer and assembly and IBM PC interface and supporting software. The main function of interface is to control the sample changer which is basically loading and unloading of sample, data acquisition and further processing by software. The pulses from detector are analysed in a pulse shape discriminator. A pulse identified as an alpha, beta or gamma event is converted to digital pulse. These digital pulses are accumulated in the three channels on PC interface each corresponding to alpha, beta and gamma. The sample movements are controlled by interface depending upon sample position. The software has been developed so as to maintain user friendliness and convenience of the operator. Various selection modes for parameters and operation of system provide lot of flexibility in operation of the system. (author). 1 fig

  1. Randomized study of initial treatment with radiationter dot MCNU or radiationter dot MCNUter dot interferon-. beta. for malignant glioma

    Energy Technology Data Exchange (ETDEWEB)

    Kiya, Katsuzo; Uozumi, Tohru; Kurisu, Kaoru (Hiroshima Univ. (Japan). School of Medicine) (and others)

    1990-02-01

    The efficacy of radiation{center dot}MCNU (MR group) or radiation{center dot}MCNU{center dot}interferon-{beta} (IMR group) for malignant glioma was studied by a randomized trial at numerous medical facilities. MR group was irradiated with 50{approx}60 Gy and intravenously injected with 2 mg/kg of MCNU on the initial day of irradiation and 6 weeks later. IMR group was also given intravenous administration of interferon-{beta} at the dose of 2x10{sup 6}IU/m{sup 2} for 5 serial-days every eight weeks. There was no difference in background between the two groups. The response rate in MR group and IMR group was 44.4% (4/9) and 30.0% (3/10), respectively, showing no significant difference. The resected tumor volume before the start of these regimens seemed to correlate the response to the treatment in both groups. The major toxicity was myelosuppression, especially using MCNU with interferon-{beta}. These results indicated that this combined therapy is effective for malignant glioma, and should be executed further trials and follow up study. (author).

  2. Effects of beta/gamma radiation on nuclear waste glasses

    Energy Technology Data Exchange (ETDEWEB)

    Weber, W.J. [Pacific Northwest National Lab., Richland, WA (United States)

    1997-07-01

    A key challenge in the disposal of high-level nuclear waste (HLW) in glass waste forms is the development of models of long-term performance based on sound scientific understanding of relevant phenomena. Beta decay of fission products is one source of radiation that can impact the performance of HLW glasses through the interactions of the emitted {beta}-particles and g-rays with the atoms in the glass by ionization processes. Fused silica, alkali silicate glasses, alkali borosilicate glasses, and nuclear waste glasses are all susceptible to radiation effects from ionization. In simple glasses, defects (e.g., non-bridging oxygen and interstitial molecular oxygen) are observed experimentally. In more complex glasses, including nuclear waste glasses, similar defects are expected, and changes in microstructure, such as the formation of bubbles, have been reported. The current state of knowledge regarding the effects of {beta}/{gamma} radiation on the properties and microstructure of nuclear waste glasses are reviewed. (author)

  3. Beta activity measurements in high, variable gamma backgrounds

    International Nuclear Information System (INIS)

    Stanga, D.; Sandu, E.; Craciun, L.

    1997-01-01

    In many cases beta activity measurements must be performed in high and variable gamma backgrounds. In such instances it is necessary to use well-shielded detectors but this technique is limited to laboratory equipment and frequently insufficient. In order to perform in a simple manner beta activity measurements in high and variable backgrounds a software-aided counting technique have been developed and a counting system have been constructed. This technique combines the different counting techniques with traditional method of successive measurement of the sample and background. The counting system is based on a programmable multi-scaler which is endowed with appropriate software and allow all operations to be performed via keyboard in an interactive fashion. Two large - area proportional detectors were selected in order to have the same background and the same gamma response within 5%. A program has been developed for the counting data analysis and beta activity computing. The software-aided counting technique has been implemented for beta activity measurement in high and variable backgrounds. (authors)

  4. Meningioma growth and interferon beta-1b treated multiple sclerosis: coincidence or relationship?

    Energy Technology Data Exchange (ETDEWEB)

    Drevelegas, A.; Xinou, E. [AHEPA University Hospital, Aristotele University School of Medicine, Department of Radiology, Thessaloniki (Greece); Karacostas, D.; Parissis, D.; Milonas, I. [AHEPA University Hospital, Aristotele University School of Medicine, B' Department of Neurology, Thessaloniki (Greece); Karkavelas, G. [AHEPA University Hospital, Aristotele University School of Medicine, Laboratory of Pathology, Thessaloniki (Greece)

    2005-07-01

    Although the coincidence of multiple sclerosis (MS) and central nervous system (CNS) tumors has been reported in over 30 cases in English literature, meningioma growth was associated with interferon-beta (INF-b) treated MS only in two of them. We report the case of a 19-year-old woman with clinically possible, laboratory supported MS, and a concomitant right intraventricular tumor with magnetic resonance imaging (MRI) characteristics consistent with meningioma (similar signal with grey matter on T1 and T2-weighted images and homogenous, intense enhancement). Two years after initiation of INF-b treatment, follow-up brain MRI revealed enlargement of the intraventricular mass and relative increase in the number of white matter lesions without significant clinical deterioration. She underwent almost total resection of the mass and histology confirmed the diagnosis of papillary meningioma. Based on the immunohistochemistry results, we speculate that INF-b resulted in meningioma growth by enhancing platelet derived growth factor (PDGF) receptors or/and down-regulating transforming growth factor receptors on the tumor itself. (orig.)

  5. Meningioma growth and interferon beta-1b treated multiple sclerosis: coincidence or relationship?

    International Nuclear Information System (INIS)

    Drevelegas, A.; Xinou, E.; Karacostas, D.; Parissis, D.; Milonas, I.; Karkavelas, G.

    2005-01-01

    Although the coincidence of multiple sclerosis (MS) and central nervous system (CNS) tumors has been reported in over 30 cases in English literature, meningioma growth was associated with interferon-beta (INF-b) treated MS only in two of them. We report the case of a 19-year-old woman with clinically possible, laboratory supported MS, and a concomitant right intraventricular tumor with magnetic resonance imaging (MRI) characteristics consistent with meningioma (similar signal with grey matter on T1 and T2-weighted images and homogenous, intense enhancement). Two years after initiation of INF-b treatment, follow-up brain MRI revealed enlargement of the intraventricular mass and relative increase in the number of white matter lesions without significant clinical deterioration. She underwent almost total resection of the mass and histology confirmed the diagnosis of papillary meningioma. Based on the immunohistochemistry results, we speculate that INF-b resulted in meningioma growth by enhancing platelet derived growth factor (PDGF) receptors or/and down-regulating transforming growth factor receptors on the tumor itself. (orig.)

  6. Multiple Sclerosis in Older Adults: The Clinical Profile and Impact of Interferon Beta Treatment

    Directory of Open Access Journals (Sweden)

    Afsaneh Shirani

    2015-01-01

    Full Text Available Background. We examined (1 patient characteristics and disease-modifying drug (DMD exposure in late-onset (LOMS, ≥50 years at symptom onset versus adult-onset (AOMS, 18–<50 years MS and (2 the association between interferon-beta (IFNβ and disability progression in older relapsing-onset MS adults (≥50 years. Methods. This retrospective study (1980–2004, British Columbia, Canada included 358 LOMS and 5627 AOMS patients. IFNβ-treated relapsing-onset MS patients aged ≥50 (regardless of onset age, 90 were compared with 171 contemporary and 106 historical controls. Times to EDSS 6 from onset and from IFNβ eligibility were examined using survival analyses. Results. LOMS patients (6% were more likely to be male, with motor onset and a primary-progressive course, and exhibit faster progression and were less likely to take DMDs. Nonetheless, 57% were relapsing-onset, of which 31% were prescribed DMDs, most commonly IFNβ. Among older relapsing-onset MS adults, no significant association between IFNβ exposure and disability progression was found when either the contemporary (hazard ratio [HR]: 0.46; 95% CI: 0.18–1.22 or historical controls (HR: 0.54; 95% CI: 0.20–1.42 were considered. Conclusion. LOMS differed clinically from AOMS. One-third of older relapsing-onset MS patients were prescribed a DMD. IFNβ exposure was not significantly associated with reduced disability in older MS patients.

  7. Interferon beta-1b reduces black holes in a randomised trial of clinically isolated syndrome.

    Science.gov (United States)

    Nagtegaal, Gijsbert J A; Pohl, Christoph; Wattjes, Mike P; Hulst, Hanneke E; Freedman, Mark S; Hartung, Hans-Peter; Miller, David; Montalban, Xavier; Kappos, Ludwig; Edan, Gilles; Pleimes, Dirk; Beckman, Karola; Stemper, Brigitte; Polman, Christoph H; Sandbrink, Rupert; Barkhof, Frederik

    2014-02-01

    Multiple sclerosis (MS) is characterised by inflammatory lesions of the central nervous system. Interferon beta-1b (IFNB-1b) has been shown to improve clinical and magnetic resonance imaging (MRI) measures for patients with MS. To evaluate whether IFNB-1b in patients presenting with clinically isolated syndromes (CIS) prevented persisting T1 hypointensities on MRI (persistent black holes (PBHs)). In the placebo-controlled phase, patients (n = 468) were initially randomised to IFNB-1b (n = 292) or placebo (n = 176) for two years or clinically definite MS (CDMS). In the open-label phase (n = 418), both groups were offered IFNB-1b for up to five years. Lesions were classified as PBHs if T1 hypointensity persisted throughout the last available scan (minimum time one year). A total of 435 patients were evaluable for analysis. The number of PBHs/patient was lower in the early rather than the delayed treatment arm during both phases (.42 vs .71, p = .0102 and .70 vs 1.17, p = .0121). Exploratory analyses identified baseline characteristics that affected rate of conversion. Although the rate of lesions that converted to PBH showed no significant differences between groups, the numbers of PBHs per patient out of new lesions was significantly lower in IFNB-1b patients compared to patients on placebo. NCT00544037.

  8. Patient preferences for Interferon-beta in Iran: A discrete choice experiment.

    Directory of Open Access Journals (Sweden)

    Farimah Rahimi

    Full Text Available Multiple sclerosis is a chronic, progressive, and common disease affecting the central nervous system in young adults. Interferon-beta is one of the most widely used medicines to reduce the disease progression. Given the variety of drugs in this category, we aimed to identify the preferences of patients for IFN-β that play an important role in policymaking in this area. Discrete choice experiment method was used in the present study to identify and prioritize those attributes that are of interest to MS patients and increases the utility of the use of IFN-β in their treatment. Questionnaires were given to 358 patients in Isfahan-Iran, who were asked to choose between the two treatment choices in each scenario. The results of the logit model showed that the changes in the efficacy lead to the most changes in the patient utility. Changes in side effects and ease of injection have been placed in the next rankings. Considering the drug attributes considered more desirable by patients can lead to greater medication adherence and possibly better treatment outcomes. Also, pharmaceutical companies, the health ministry, the Food and Drug Administration, insurance organizations, and neurologists can benefit from this information in production and importation, policymaking, and prescription.

  9. Association of interferon-gamma and interleukin 10 genotypes and serum levels with partial clinical remission in type 1 diabetes

    DEFF Research Database (Denmark)

    Alizadeh, B Z; Hanifi-Moghaddam, P; Eerligh, P

    2006-01-01

    We studied whether serum interferon (IFN)-gamma or interleukin (IL)-10 levels and their corresponding functional polymorphic genotypes are associated with partial remission of type 1 diabetes (T1D). A multi-centre study was undertaken in patients with newly diagnosed T1D and matched controls. T1D...

  10. Surface plasmon resonance biosensor based on engineered proteins for direct detection of interferon-gamma in diluted blood plasma

    Czech Academy of Sciences Publication Activity Database

    Šípová, Hana; Ševců, Veronika; Kuchař, Milan; Ahmad, Jawid Nazir; Mikulecký, Pavel; Osičková, Adriana; Malý, Petr; Homola, Jiří

    2012-01-01

    Roč. 174, č. 11 (2012), s. 306-311 ISSN 0925-4005 R&D Projects: GA AV ČR KAN200670701 Institutional support: RVO:67985882 ; RVO:61388971 ; RVO:86652036 Keywords : Interferon gamma * Surface plasmon resonance * Biosensor Subject RIV: JB - Sensors, Measurment, Regulation Impact factor: 3.535, year: 2012

  11. Study on Anti-Hepatitis B Surface Antibody Titer and Specific Interferon Gamma Response Among Dentists

    Directory of Open Access Journals (Sweden)

    Manoochehr Makvandi

    2017-01-01

    Full Text Available Background Hepatitis B virus (HBV is a major problem for healthcare workers worldwide, and among them, dentists are at risk of acquiring HBV infection. The prevalence of HBV infection has been reported among the dentists in different regions of the world. Since none of the available drugs can clear HBV infection, the presence of effective immunity against HBV infection is important to prevent HBV infection. Objectives This study aimed at determining HBs antibody and specific HBV gamma interferon among the dentists, who received hepatitis B vaccine. Methods The blood samples were collected from 40 dentists, including 7 endodontics, 2 oral and maxillofacial radiologist, 4 periodontics, 11 oral and maxillofacial surgeons, 6 implantologists, 3 orthodontics, 1 oral and maxillofacial pathologist, 2 esthetic and restorative dentists, and 4 doctors of dental surgery (DDS at from dental college of Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran during December, 2013. Overall, 31 (77.5% dentists had already received 3 doses of recombinant hepatitis B vaccine, and 9 (22.5% had received only two doses of the vaccine. Their sera were tested for HBsAb and anti-HBc-IgG by the Enzyme Linked Immunosorbent Assay (ELISA test. The lymphocyte of individuals was separated from their blood sample by Ficoll-Hypaque, cells were washed with phosphate buffered saline (PBS by centrifugation, and finally the pellet cells was resuspended in RPMI-1640 media. Separated cells were exposed to 2.5 µg of purified recombinant HBs antigen, and supernatants were collected after 72 hours and tested for detection of specific interferon γ level by ELISA test. Results Overall, 97.5% of dentists showed positive HBs antibody test results while 36 showed (90% positive test results for specific interferon γ against hepatitis B virus infection. Conclusions High coverage of 97.5% immune response against hepatitis B infection was found, indicating high efficacy of recombinant

  12. Heterogeneity within populations of recombinant Chinese hamster ovary cells expressing human interferon-gamma.

    Science.gov (United States)

    Coppen, S R; Newsam, R; Bull, A T; Baines, A J

    1995-04-20

    The Chinese hamster ovary (CHO) cell line has great commercial importance in the production of recombinant human proteins, especially those for therapeutic use. Much attention has been paid to CHO cell population physiology in order to define factors affecting product fidelity and yield. Such studies have revealed that recombinant proteins, including human interferon-gamma (IFN-gamma), can be heterogeneous both in glycosylation and in proteolytic processing. The type of heterogeneity observed depends on the growth physiology of the cell population, although the relationship between them is complex. In this article we report results of a cytological study of the CHO320 line which expresses recombinant human IFN-gamma. When grown in suspension culture, this cell line exhibited three types of heterogeneity: (1) heterogeneity of the production of IFN-gamma within the cell population, (2) heterogeneity of the number of nuclei and mitotic spindles in dividing cells, and (3) heterogeneity of cellular environment. The last of these arises from cell aggregates which form in suspension culture: Some cells are exposed to the culture medium; others are fully enclosed within the mass with little or no direct access to the medium. Thus, live cells producing IFN-gamma are heterogeneous in their environment, with variable access to O(2) and nutrients. Within the aggregates, it appears that live cells proliferate on a dead cell mass. The layer of live cells can be several cells deep. Specific cell-cell attachments are observed between the living cells in these aggregates. Two proteins, known to be required for the formation of certain types of intercellular junctions, spectrin and vinculin, have been localized to the regions of cell-cell contact. The aggregation of the cells appears to be an active process requiring protein synthesis. (c) 1995 John Wiley & Sons, Inc.

  13. An interferon-gamma release assay test performs well in routine screening for tuberculosis

    DEFF Research Database (Denmark)

    Vestergaard Danielsen, Allan; Fløe, Andreas; Lillebæk, Troels

    2014-01-01

    Introduction: A positive interferon-gamma release assay (IGRA) is regarded as proof of latent Mycobacterium tuberculosis infection. We conducted an evaluation of the IGRA test “T-SPOT.TB” to test its performance during clinical routine use by analysing the positivity rate and odds, effect of season...... and sensitivity. Material and methods: Data from T-SPOT.TB testing together with age and test indications (anti-tumour necrosis factor alpha (TNFα) candidate, contact investigation or suspicion of tuberculosis (TB)) were combined with mycobac­teria culture results. Results: A total of 1,809 patients were tested....... Conclusive results were achieved for 1,780 patients (98.4%). Among these, 4.6% of anti-TNFα candidates, 19.3% of contacts and 24.4% of TB suspects tested positive. Compared with anti-TNFα candidates, the odds for a positive result were significantly higher for contact investigations (odds ratio (OR), mean...

  14. Interleukin-4 (IL-4) and Interferon-Gamma (IFN-gamma) in pregnant ...

    African Journals Online (AJOL)

    Background and Objective:- To assess if gestational factors affect the resistance of C57BL/6 mice to L. major infection, this study determined the levels of IL-4 and IFN-gamma in popliteal lymph node cells of pregnant C57BL/6 mice infected with L. major at 16 hours, 5 days-, 10 days- and 15 days- post plug by PCR, ELISA ...

  15. Skin dose assessment in routine personnel beta/gamma dosimetry

    International Nuclear Information System (INIS)

    Christensen, P.

    1980-01-01

    The International Commission on Radiological Protection (Publication 26) has recommended a tissue depth of 5 to 10 mg.cm -2 for skin dose assessments. This requirement is generally not fulfilled by routine monitoring procedures because of practical difficulties in using very thin dosemeters with low sensitivity and therefore a high minimum detectable dose. Especially for low-energy beta-ray exposures underestimations of the skin dose by a factor of more than ten may occur. Low-transparent graphite-mixed sintered LiF and Li 2 B 4 0 7 : Mn dosemeters were produced which show a skin-equivalent response to beta and gamma exposures over a wide range of energies. These have found wide-spread application for extremity dosimetry but have not yet been generally introduced in routine personnel beta/gamma monitoring. The following adaptations of existing routine monitoring systems for improved skin dose assessments have been investigated: 1) Placement of a supplementary, thin, skin-dose equivalent dosemeter in the TLD badge to give additional information on low-energy exposures. 2) Introduction of a second photomultiplier in the read-out chamber which enables a simultaneous determination of emitted TL from both sides of the dosemeter separately. This method makes use of the selfshielding of the dosemeter to give information on the low-energy dose contribution. 3) By diffusion of Li 2 B 4 0 7 into solid LiF-dosemeters it was possible to produce a surface layer with a new distinct glow-peak at about 340 deg C which is not present in the undiffused part of the LiF chip, and which can be utilized for the assessment of the skin-dose. Data on energy response and accuracy of dose measurement for beta/gamma exposures are given for the three methods and advantages and disadvantages are discussed (H.K.)

  16. Interferon beta-1a in chronic inflammatory demyelinating polyneuropathy: case report Interferon beta en polineuropatía crónica inflamatoria desmienlinizante: caso clínico

    Directory of Open Access Journals (Sweden)

    Andrés Maria Villa

    2004-09-01

    Full Text Available Chronic inflammatory demyelinating polyneuropathy (CIDP is an acquired immune-mediated neuropathy. It presents with a course of progression which may be slow and steady or step-wise or relapsing. Sensory ataxic polyneuropathy may be the only clinical manifestation of this disease. Treatment with interferon beta1a (INF beta1a has been tried with different results in patients who were refractory to other, more conventional, immunomodulatory therapies. Here we report on a patient who had a relapsing form of pure sensory ataxic CIDP and who failed to respond to intravenous human immunoglobulin. He was put on INF beta1a for 3 years. During this period he suffered no relapses while his condition stabilized.La polineuropatía crónica inflamatoria desmielinizante (PCID es una neuropatía inmuno-mediada, que presenta un curso clínico primariamente progresivo o en forma de recaídas. Las manifestaciones sensoriales pueden ser su unica forma de expresión clínica. El tratamiento con interferon beta 1a (IFN beta1a ha sido ensayado en varias oportunidades, con diferentes respuestas terapéuticas, en pacientes refractarios a las terapias inmunomoduladoras convencionales. Nosotros comunicamos un paciente con una forma ataxica recurrente de PCID, que no respondió al tratamiento con inmunoglobulina endovenosa. Posteriormente fue tratado con IFN beta 1 a por tres años. Durante el período de seguimiento no mostró nuevas recaídas y su cuadro neurológico se estabilizó.

  17. High-$\\gamma$ Beta Beams within the LAGUNA design study

    CERN Document Server

    Orme, Christopher

    2010-01-01

    Within the LAGUNA design study, seven candidate sites are being assessed for their feasibility to host a next-generation, very large neutrino observatory. Such a detector will be expected to feature within a future European accelerator neutrino programme (Superbeam or Beta Beam), and hence the distance from CERN is of critical importance. In this article, the focus is a $^{18}$Ne and $^{6}$He Beta Beam sourced at CERN and directed towards a 50 kton Liquid Argon detector located at the LAGUNA sites: Slanic (L=1570 km) and Pyh\\"{a}salmi (L=2300 km). To improve sensitivity to the neutrino mass ordering, these baselines are then combined with a concurrent run with the same flux directed towards a large Water \\v{C}erenkov detector located at Canfranc (L=650 km). This degeneracy breaking combination is shown to provide comparable physics reach to the conservative Magic Baseline Beta Beam proposals. For $^{18}$Ne ions boosted to $\\gamma=570$ and $^{6}$He ions boosted to $\\gamma=350$, the correct mass ordering can be...

  18. Equine interferon gamma synthesis in lymphocytes after in vivo infection and in vitro stimulation with EHV-1.

    Science.gov (United States)

    Paillot, R; Daly, J M; Juillard, V; Minke, J M; Hannant, D; Kydd, J H

    2005-08-22

    Equine cytotoxic T lymphocyte (CTL) responses to equine herpesvirus-1 (EHV-1) are well characterised but little is known about the cytokine response after infection or vaccination. EHV-1 is common in horses and infects lymphocytes in vivo. This virus was used as a model to measure the synthesis of interferon gamma (IFN-gamma) by equine peripheral blood mononuclear cells (PBMC) after in vivo infection and/or in vitro stimulation with EHV-1. Both flow cytometry and ELISPOT assays were used to quantify equine IFN-gamma using a mouse anti-bovine IFN-gamma monoclonal antibody (clone CC302; shown to cross-react with recombinant equine IFN-gamma) and a rabbit anti-canine IFN-gamma polyclonal antibody. The percentage of PBMC synthesising IFN-gamma after in vitro stimulation with EHV-1 increased with age. In yearlings infected experimentally with EHV-1, PBMC showed two peaks of IFN-gamma synthesis, 11 and 56 days after infection. The IFN-gamma synthesis was principally associated with CD8(+) cells. The patterns of IFN-gamma synthesis detected by intracellular IFN-gamma staining or ELISPOT were compared with CTL data and shown to be similar. These methods were also applied successfully to frozen samples of PBMC. Measurement of equine IFN-gamma using these simple techniques can now be applied to future studies on protective cellular immune responses following virus infection and/or vaccination of horses.

  19. Interferon beta induces apoptosis in nasopharyngeal carcinoma cells via the TRAIL-signaling pathway.

    Science.gov (United States)

    Makowska, Anna; Wahab, Lora; Braunschweig, Till; Kapetanakis, Nikiforos-Ioannis; Vokuhl, Christian; Denecke, Bernd; Shen, Lian; Busson, Pierre; Kontny, Udo

    2018-03-06

    The combination of neoadjuvant chemotherapy, radiochemotherapy, and maintenance therapy with interferon beta (IFNβ) has led to superior results in the treatment of children and adolescents with nasopharyngeal carcinoma (NPC). However, nothing is known about the mechanism of the antitumor activity of IFNβ in NPC. Here, we investigate the role of IFNβ on apoptosis in NPC cells. Six NPC cell lines, one patient-derived NPC xenograft (PDX) and one SV40-transformed nasoepithelial cell line were used. Induction of apoptosis by IFNβ was measured by flow cytometric analysis of subG1-DNA-content, Hoechst 33258 staining and activation of caspase-3. Dissection of death ligand signaling pathways included measuring surface expression of its components by flow cytometry, activation by death ligands and neutralization with specific antibodies and siRNA. IFNβ induced apoptosis at concentrations achievable in humans in five of six NPC cell lines and in PDX cells but not in nasoepithelial cells. Inhibition of caspases-3 and -8 abrogated this effect suggesting IFNβ promoted apoptosis through the extrinsic pathway. IFNβ induced surface expression of TRAIL and TRAIL-R2 and the addition of an anti-TRAIL-antibody or transfection with TRAIL-siRNA blocked IFNβ-induced apoptosis. No induction of TRAIL-expression was noted in the IFNβ-resistant cell line. In conclusion, IFNβ leads to apoptosis in NPC cells in an autocrine way via the induction of TRAIL expression and subsequent activation of the TRAIL-signaling pathway. The mechanism described could at least partly explain the clinical benefit of IFNβ in the treatment of NPC. Further studies in a mouse-xenograft model are warranted to substantiate this effect in vivo .

  20. Effects of type I/type II interferons and transforming growth factor-beta on B-cell differentiation and proliferation. Definition of costimulation and cytokine requirements for immunoglobulin synthesis and expression.

    Science.gov (United States)

    Estes, D M; Tuo, W; Brown, W C; Goin, J

    1998-12-01

    In this report, we sought to determine the role of selected type I interferons [interferon-alpha (IFN-alpha) and interferon-tau (IFN-tau)], IFN-gamma and transforming growth factor-beta (TGF-beta) in the regulation of bovine antibody responses. B cells were stimulated via CD40 in the presence or absence of B-cell receptor (BCR) cross-linking. IFN-alpha enhanced IgM, IgG2 and IgA responses but did not enhance IgG1 responses. BCR signalling alone was more effective at inducing IgG2 responses with IFN-alpha than dual cross-linking with CD40. Recombinant ovine IFN-tau was less effective at inducing IgG2 responses when compared with IFN-alpha, though IgA responses were similar in magnitude following BCR cross-linking. At higher concentrations, IFN-tau enhanced IgA responses greater than twofold over the levels observed with IFN-alpha. Previous studies have shown that addition of IFN-gamma to BCR or pokeweed mitogen-activated bovine B cells stimulates IgG2 production. However, following CD40 stimulation alone, IFN-gamma was relatively ineffective at stimulating high-rate synthesis of any non-IgM isotype. Dual cross-linking via CD40 and the BCR resulted in decreased synthesis of IgM with a concomitant increase in IgA and similar levels of IgG2 production to those obtained via the BCR alone. We also assessed the effects of endogenous and exogenous TGF-beta on immunoglobulin synthesis by bovine B cells. Exogenous TGF-beta stimulates both IgG2 and IgA production following CD40 and BCR cross-linking in the presence of IL-2. Blocking endogenous TGF-beta did not inhibit the up-regulation of IgG2 or IgA by interferons.

  1. Identification of new sensitive biomarkers for the in vivo response to interferon-beta treatment in multiple sclerosis using DNA-array evaluation

    DEFF Research Database (Denmark)

    Sellebjerg, F.; Krakauer, M.; Hesse, D.

    2009-01-01

    Neutralizing antibodies (NAbs) occur in a proportion of multiple sclerosis (MS) patients treated with interferon (IFN)-beta. NAbs impair the effect of treatment. The biological effect of IFN-beta can be measured as the induction of the myxovirus resistance protein A (MxA) molecule. However, other...

  2. Recombinant gamma interferon for the treatment of pulmonary and mycobacterial diseases

    International Nuclear Information System (INIS)

    Garcia, Idrian; Milanes, Maria T; Cayon, Isis; Santos, Yamilet et. al

    2009-01-01

    An increased antibiotic resistance is described for Mycobacterium tuberculosis and atypical mycobacterial species; therefore, new treatments are required. Immunocompromised patients have increased risk, as demonstrated by complications after BCG vaccination. On the other hand, idiopathic pulmonary fibrosis is a fatal disease, with no therapy available to modify course of the disease. Gamma interferon (IFN-γ) plays an essential role as main activator of cytokine secretion in macrophages, also showing a potent anti-fibrotic effects. To evaluate the adjuvant effect of IFN-γ on these three clinical scenarios, five clinical trials were carried out. Patients treated with IFN gamma had satisfactory response according to clinical, imaging and functional criteria since their first evaluations, significantly improving when compared to the control group receiving placebo in a study of pulmonary atypical mycobacteriosis. Fast sputum conversion was obtained in mycobacterial infections, including tuberculosis. In the idiopathic pulmonary fibrosis study, 75% of treated patients were considered as responders (improvement + stable). Here we report the cases of two nursing babies with suppurative regional lymphadenitis caused by BCG, who were successfully treated with recombinant human IFN-γ. Treatment was well tolerated, with most of the adverse reactions corresponding to classical flu-like symptoms produced by the cytokine. We can conclude that IFN-γ is useful and well tolerated as adjuvant therapy in patients with pulmonary mycobacterial diseases or idiopathic pulmonary fibrosis. (author)

  3. Resting-state beta and gamma activity in Internet addiction.

    Science.gov (United States)

    Choi, Jung-Seok; Park, Su Mi; Lee, Jaewon; Hwang, Jae Yeon; Jung, Hee Yeon; Choi, Sam-Wook; Kim, Dai Jin; Oh, Sohee; Lee, Jun-Young

    2013-09-01

    Internet addiction is the inability to control one's use of the Internet and is related to impulsivity. Although a few studies have examined neurophysiological activity as individuals with Internet addiction engage in cognitive processing, no information on spontaneous EEG activity in the eyes-closed resting-state is available. We investigated resting-state EEG activities in beta and gamma bands and examined their relationships with impulsivity among individuals with Internet addiction and healthy controls. Twenty-one drug-naïve patients with Internet addiction (age: 23.33 ± 3.50 years) and 20 age-, sex-, and IQ-matched healthy controls (age: 22.40 ± 2.33 years) were enrolled in this study. Severity of Internet addiction was identified by the total score on Young's Internet Addiction Test. Impulsivity was measured with the Barratt Impulsiveness Scale-11 and a stop-signal task. Resting-state EEG during eyes closed was recorded, and the absolute/relative power of beta and gamma bands was analyzed. The Internet addiction group showed high impulsivity and impaired inhibitory control. The generalized estimating equation showed that the Internet-addiction group showed lower absolute power on the beta band than did the control group (estimate = -3.370, p Internet-addiction group showed higher absolute power on the gamma band than did the control group (estimate = 0.434, p Internet addiction as well as with the extent of impulsivity. The present study suggests that resting-state fast-wave brain activity is related to the impulsivity characterizing Internet addiction. These differences may be neurobiological markers for the pathophysiology of Internet addiction. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Hanford beta-gamma personnel dosimeter prototypes and evaluation

    International Nuclear Information System (INIS)

    Fix, J.J.; Holbrook, K.L.; Soldat, K.L.

    1983-04-01

    Upgraded and modified Hanford dosimeter prototypes were evaluated for possible use at Hanford as a primary beta-gamma dosimeter. All prototypes were compatible with the current dosimeter card and holder design, as well as processing with the automated Hanford readers. Shallow- and deep-dose response was determined for selected prototypes using several beta sources, K-fluorescent x rays and filtered x-ray techniques. All prototypes included a neutron sensitive chip. A progressive evaluation of the performance of each of the upgrades to the current dosimeter is described. In general, the performance of the current dosimeter can be upgraded using individual chip sensitivity factors to improve precision and an improved algorithm to minimize bias. The performance of this dosimeter would be adequate to pass all categories of the ANSI N13.11 performance criteria for dosimeter procesors, provided calibration techniques compatible with irradiations adopted in the standard were conducted. The existing neutron capability of the dosimeter could be retained. Better dosimeter performance to beta-gamma radiation can be achieved by modifying the Hanford dosimeter so that four of the five chip positions are devoted to calculating these doses instead of the currently used two chip positions. A neutron sensitive chip was used in the 5th chip position, but all modified dosimeter prototypes would be incapable of discriminating between thermal and epithermal neutrons. An improved low energy beta response can be achieved for the current dosimeter and all prototypes considered by eliminating the security credential. Further improvement can be obtained by incorporating the 15-mil thick TLD-700 chips

  5. Beta-gamma counting system for Xe fission products

    International Nuclear Information System (INIS)

    Reeder, P.L.; Bowyer, T.W.; Perkins, R.W.

    1998-01-01

    A beta-gamma coincidence counting system has been developed for automated analysis of Xe gas samples separated from air. The Xe gas samples are contained in a cylindrical plastic scintillator cell located between two NaI(Tl) scintillation detectors. The X-ray and gamma spectra gated by coincident events in the plastic scintillator cell are recorded for each NaI(Tl) crystal. The characteristic signatures of the 131m Xe, 133g Xe, 133m Xe, and 135g Xe isotopes of interest for nuclear test-ban verification as well as the procedures and results of absolute efficiency measurements are described. A NaI(Tl) crystal with provision for 4 sample cells has been implemented for the system to be deployed in the field. Examples of data on ambient air samples in New York City obtained with the field prototype are presented. (author)

  6. Beta-gamma contaminated solid waste incinerator facility

    International Nuclear Information System (INIS)

    Hootman, H.E.

    1979-10-01

    This technical data summary outlines a reference process to provide a 2-stage, 400 lb/hour incinerator to reduce the storage volume of combustible process waste contaminated with low-level beta-gamma emitters in response to DOE Manual 0511. This waste, amounting to more than 200,000 ft 3 per year, is presently buried in trenches in the burial ground. The anticipated storage volume reduction from incineration will be a factor of 20. The incinerator will also dispose of 150,000 gallons of degraded solvent from the chemical separations areas and 5000 gallons per year of miscellaneous nonradioactive solvents which are presently being drummed for storage

  7. Tula and Puumala hantavirus NSs ORFs are functional and the products inhibit activation of the interferon-beta promoter.

    Science.gov (United States)

    Jääskeläinen, Kirsi M; Kaukinen, Pasi; Minskaya, Ekaterina S; Plyusnina, Angelina; Vapalahti, Olli; Elliott, Richard M; Weber, Friedemann; Vaheri, Antti; Plyusnin, Alexander

    2007-10-01

    The S RNA genome segment of hantaviruses carried by Arvicolinae and Sigmodontinae rodents encodes the nucleocapsid (N) protein and has an overlapping (+1) open reading frame (ORF) for a putative nonstructural protein (NSs). The aim of this study was to determine whether the ORF is functional. A protein corresponding to the predicted size of Tula virus (TULV) NSs was detected using coupled in vitro transcription and translation from a cloned S segment cDNA, and a protein corresponding to the predicted size of Puumala virus (PUUV) NSs was detected in infected cells by Western blotting with an anti-peptide serum. The activities of the interferon beta (IFN-beta) promoter, and nuclear factor kappa B (NF-kappaB)- and interferon regulatory factor-3 (IRF-3) responsive promoters, were inhibited in COS-7 cells transiently expressing TULV or PUUV NSs. Also IFN-beta mRNA levels in IFN-competent MRC5 cells either infected with TULV or transiently expressing NSs were decreased. These data demonstrate that Tula and Puumala hantaviruses have a functional NSs ORF. The findings may explain why the NSs ORF has been preserved in the genome of most hantaviruses during their long evolution and why hantavirus-infected cells secrete relatively low levels of IFNs. (c) 2007 Wiley-Liss, Inc.

  8. Involvement of T cells in enhanced resistance to Klebsiella pneumoniae septicemia in mice treated with liposome-encapsulated muramyl tripeptide phosphatidylethanolamine or gamma interferon

    NARCIS (Netherlands)

    Hagen, ten T.L.; Vianen, van W.; Savelkoul, H.F.J.; Heremans, H.; Buurman, W.A.; Bakker-Woudenberg, I.A.

    1998-01-01

    We have previously shown that prophylactic administration of the liposome-encapsulated immunomodulating agents muramyl tripeptide phosphatidylethanolamine (MTPPE) and gamma interferon (IFN-) results in strongly increased survival of mice from a normally lethal septicemia with Klebsiella pneumoniae.

  9. Stromal cells and osteoclasts are responsible for exacerbated collagen-induced arthritis in interferon-beta-deficient mice

    DEFF Research Database (Denmark)

    Treschow, Alexandra P; Teige, Ingrid; Nandakumar, Kutty S

    2005-01-01

    OBJECTIVE: Clinical trials using interferon-beta (IFNbeta) in the treatment of rheumatoid arthritis have shown conflicting results. We undertook this study to understand the mechanisms of IFNbeta in arthritis at a physiologic level. METHODS: Collagen-induced arthritis (CIA) was induced in IFNbeta....... Differences in osteoclast maturation were determined in situ by histology of arthritic and naive paws and by in vitro maturation studies of naive bone marrow cells. The importance of IFNbeta-producing fibroblasts was determined by transferring fibroblasts into mice at the time of CIA immunization. RESULTS...

  10. [Allergic asthma and interleukins 2, 4, 5, 6 and 12 and gamma interferon levels].

    Science.gov (United States)

    Bastida Segura, Diana Lyzbeth; López Velásquez, Benjamin; Castrejón Vázquez, María Isabel; Galicia Tapía, Jorge; Cano Altamirano, Silvia; Miranda Feria, Alfonso Javier

    2004-01-01

    Asthma is an inflammatory chronic illness, in which mastocyt cells, basophils, T lymphocytes, eosinophils and cytokines play a role. Its association with the production of TH2 cytokines is not well known, but it is considered an aberrant immune response, yielding the activation and recruitment of a number of effector cells (mastocyts/eosinophils) and the appearance of clinical symptoms. To determine the serum values of the interleukins 2, 4, 5, 6 and 12 and gamma interferon in relation to the severity degree of asthma and the time of immunotherapy in patients with stable chronic allergic bronchial asthma. Clinical records of allergic asthmatic patients from the external consultation at Servicio de Alergia e Immunología Clínica were reviewed in a period of 12 months (1st January 2002 to 1st January 2003) and those of healthy volunteers, forming three groups: Group 1, allergic asthmatics with immunotherapy less than 24 months; Group 2, allergic asthmatics with more than 24 months of immunotherapy, and Group 3, healthy volunteers (control group). Previous informed consent, a serum sample was taken of all subjects. Ninety-two subjects were included: 41 (45%) allergic asthmatics and 51 (55%) healthy volunteers. Significant differences were found in interleukins 2, 4, 5, 6 and 12 levels between healthy volunteers and asthmatics without relating the immunotherapy time. In the total group gamma interferon levels were not found. A relation of interleukins Th2 levels with the severity degree of asthma was not found. Differences of serum interleukins Th1 and Th2 in allergic patients related to immunotherapy time were not significant; even though, irrespective of immunotherapy time, IgG levels were always high. Patients with allergic asthma have a predominance of serum interleukins Th2 and, despite of the immunotherapy, in the maintaining phase, these continue high, which may be due to an immune system dysregulation maybe including other factors. Immunotherapy continues

  11. Executive Summary of the Guidelines for the Use of interferon-gamma Release Assays in the Diagnosis of Tuberculosis Infection.

    Science.gov (United States)

    Santin, Miguel; García-García, José-María; Rigau, David; Altet, Neus; Anibarro, Luis; Casas, Irma; Díez, Nuria; García-Gasalla, Mercedes; Martínez-Lacasa, Xavier; Penas, Antón; Pérez-Escolano, Elvira; Sánchez, Francisca; Domínguez, José

    2016-09-01

    Interferon-gamma release assays are widely used for the diagnosis of tuberculosis infection in Spain. However, there is no consensus on their application in specific clinical scenarios. To develop a guide-line for their use, a panel of experts comprising specialists in infectious diseases, respiratory diseases, microbiology, pediatrics and preventive medicine, together with a methodologist, conducted a systematic literature search, summarized the findings, rated the quality of the evidence, and formulated recommendations following the Grading of Recommendations of Assessment Development and Evaluations methodology. This document provides evidence-based guidance on the use of interferon-gamma release assays for the diagnosis of tuberculosis infection in patients at risk of tuberculosis or suspected of having active disease. The guidelines will be applicable to specialist and primary care, and public health. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Gamma-interferon bioassay for detection of bovine tuberculosis in cattle: kinetics of production and dose response in whole blood culture

    International Nuclear Information System (INIS)

    Bhatia, Sandeep; Das, S.K.

    1999-01-01

    Stimulation with mycobacterium bovis PPD sensitised lymphocytes (whole blood or peripheral blood lymphocytes) results in release of gamma-interferon that can be detected by simple bioassay. The optimum concentration of bovine PPD was 20 μg ml and the optimum incubation period was 24 hr for maximum production of gamma-interferon in whole blood culture (128 units/ml) and peripheral blood culture (64 units/ml). (author)

  13. Proliferative and antiproliferative effects of interferon-gamma and tumor necrosis factor-alpha on cell lines derived from cervical and ovarian malignancies

    International Nuclear Information System (INIS)

    Mutch, D.G.; Massad, L.S.; Kao, M.S.; Collins, J.L.

    1990-01-01

    Four human cell lines derived from cervical carcinomas (ME-180, SiHa, HT-3, and MS751) and three human cell lines derived from ovarian carcinomas (SK-OV-3, Caov-3, and NIH:OVCAR-3) were analyzed in vitro to determine the effect of recombinant interferon-gamma and recombinant human tumor necrosis factor-alpha on cell growth and survival. The effects of interferon-gamma, tumor necrosis factor-alpha, and both interferon-gamma and tumor necrosis factor-alpha on cell growth were measured after 24 and 72 hours of incubation by the incorporation of chromium 51. The results of this analysis showed that all seven cell lines were resistant to the antiproliferative action of tumor necrosis factor-alpha, that the growth of most cell lines was inhibited by interferon-gamma by 72 hours of incubation, and that after 72 hours of incubation all cell lines demonstrated a synergistic antiproliferative response to the combination of interferon-gamma and tumor necrosis factor-alpha. However, the effects of these cytokines on cell growth were found to differ among cell lines and varied with the concentration and the duration of incubation. The growth of one cell line (Caov-3) was stimulated by both tumor necrosis factor-alpha and interferon-gamma. These results suggest that the clinical effects of these cytokines on the growth of gynecologic cancers may be more complex than previously supposed

  14. Beta and gamma decay heat evaluation for the thermal fission of 235U

    International Nuclear Information System (INIS)

    Schenter, G.K.; Schmittroth, F.

    1979-01-01

    Beta and gamma fission product decay heat curves are evaluated for the thermal fission of 235 U. Experimental data that include beta, gamma, and total measurements are combined with summation calculations based on ENDF/B in a consistent evaluation. Least-squares methods are used that take proper account of data uncertainties and correlations. 4 figures, 2 tables

  15. Enhancing effects of gamma interferon on phagocytic cell association with and killing of Trypanosoma cruzi

    Science.gov (United States)

    Wirth, J. J.; Kierszenbaum, F.; Sonnenfeld, G.; Zlotnik, A.

    1985-01-01

    Results are reported from a study of the influence gamma interferon (GIFN) and interleukin 2 (IL2) have on the capability of P388D1 cells and mouse resident peritoneal macrophages (MPM) to attach to the blood-resident parasites Trypanosoma cruzi and kill them. Cultures of trypomastigote forms of the Tulahuen strain of T. cruzi grown in bovine serum were introduced into peritoneal cells of mice, along with P388D1 cells incubated with GIFN, IL2 and both. Control cells were also maintained. Statistical analysis were then performed on data on counts of the number of dead T. Cruzi cells. The GIFN enhanced the interaction of MPM and P388D1 cells with the surface of T. Cruzi, provided the interaction was given over 12 hr to take place. A depression of the cytotoxicity of P388D1 cells was attributed to mediation by H2O2, an effect partially offset by incubation with the lymphokine GIFN.

  16. MOLECULAR CLONING, SEQUENCING, EXPRESSION AND BIOLOGICAL ACTIVITY OF GIANT PANDA (AILUROPODA MELANOLEUCA) INTERFERON-GAMMA.

    Science.gov (United States)

    Zhu, Hui; Wang, Wen-Xiu; Wang, Bao-Qin; Zhu, Xiao-Fu; Wu, Xu-Jin; Ma, Qing-Yi; Chen, De-Kun

    2012-06-29

    The giant panda (Ailuropoda melanoleuca) is an endangered species and indigenous to China. Interferon-gamma (IFN-γ) is the only member of type □ IFN and is vital for the regulation of host adapted immunity and inflammatory response. Little is known aboutthe FN-γ gene and its roles in giant panda.In this study, IFN-γ gene of Qinling giant panda was amplified from total blood RNA by RT-CPR, cloned, sequenced and analysed. The open reading frame (ORF) of Qinling giant panda IFN-γ encodes 152 amino acidsand is highly similar to Sichuan giant panda with an identity of 99.3% in cDNA sequence. The IFN-γ cDNA sequence was ligated to the pET32a vector and transformed into E. coli BL21 competent cells. Expression of recombinant IFN-γ protein of Qinling giant panda in E. coli was confirmed by SDS-PAGE and Western blot analysis. Biological activity assay indicated that the recombinant IFN-γ protein at the concentration of 4-10 µg/ml activated the giant panda peripheral blood lymphocytes,while at 12 µg/mlinhibited. the activation of the lymphocytes.These findings provide insights into the evolution of giant panda IFN-γ and information regarding amino acid residues essential for their biological activity.

  17. Gamma interferon-induced guanylate binding protein 1 is a novel actin cytoskeleton remodeling factor.

    Science.gov (United States)

    Ostler, Nicole; Britzen-Laurent, Nathalie; Liebl, Andrea; Naschberger, Elisabeth; Lochnit, Günter; Ostler, Markus; Forster, Florian; Kunzelmann, Peter; Ince, Semra; Supper, Verena; Praefcke, Gerrit J K; Schubert, Dirk W; Stockinger, Hannes; Herrmann, Christian; Stürzl, Michael

    2014-01-01

    Gamma interferon (IFN-γ) regulates immune defenses against viruses, intracellular pathogens, and tumors by modulating cell proliferation, migration, invasion, and vesicle trafficking processes. The large GTPase guanylate binding protein 1 (GBP-1) is among the cellular proteins that is the most abundantly induced by IFN-γ and mediates its cell biologic effects. As yet, the molecular mechanisms of action of GBP-1 remain unknown. Applying an interaction proteomics approach, we identified actin as a strong and specific binding partner of GBP-1. Furthermore, GBP-1 colocalized with actin at the subcellular level and was both necessary and sufficient for the extensive remodeling of the fibrous actin structure observed in IFN-γ-exposed cells. These effects were dependent on the oligomerization and the GTPase activity of GBP-1. Purified GBP-1 and actin bound to each other, and this interaction was sufficient to impair the formation of actin filaments in vitro, as demonstrated by atomic force microscopy, dynamic light scattering, and fluorescence-monitored polymerization. Cosedimentation and band shift analyses demonstrated that GBP-1 binds robustly to globular actin and slightly to filamentous actin. This indicated that GBP-1 may induce actin remodeling via globular actin sequestering and/or filament capping. These results establish GBP-1 as a novel member within the family of actin-remodeling proteins specifically mediating IFN-γ-dependent defense strategies.

  18. Epitope and functional specificity of monoclonal antibodies to mouse gamma interferon: the synthetic peptide approach

    International Nuclear Information System (INIS)

    Russell, J.K.; Hayes, M.P.; Carter, J.M.; Torres, B.A.; Dunn, B.M.; Johnson, H.M.

    1986-01-01

    Four anti-recombinant mouse gamma interferon (α-IFNγ) monoclonal antibodies were generated using hamster spleen cells. Binding of 125 I-IFNγ by these protein A-bound antibodies was specifically blocked by cold IFNγ. Binding by three of these antibodies was also blocked by a synthetic peptide corresponding to the N-terminal 1-39 amino acids of IFNγ, while a corresponding C-terminal (95-133) peptide had no effect on binding. One of the N-terminal specific monoclonal antibodies inhibited both the antiviral and macrophage priming (for tumor cell killing) activities of IFNγ, while the other two had no effect on either biological function. Blocking experiments with cold IFNγ and N-terminal peptide suggest that the epitope specificities of the monoclonal antibodies could be determined by the conformational or topographic structure of IFNγ. Polyclonal antibodies to either the N-terminal or C-terminal peptides also inhibited both the antiviral and macrophage priming activities of IFNγ. All of the antibodies that inhibited IFNγ function also blocked binding of IFNγ to membrane receptor on cells, while antibodies that did not inhibit function also did not block binding. The data suggest that both the N-terminal and C-terminal domains of IFNγ play an important role in its antiviral and macrophage priming functions, possibly in a cooperative manner

  19. Association between level of interferon gamma and acid-fast bacillipositivity in pulmonary tuberculosis

    Science.gov (United States)

    Priwahyuningtyas, N. B.; Sinaga, B. Y. M.; Pandia, P.; Eyanoer, P. C.

    2018-03-01

    Tuberculosis is an infectious disease which caused by Mycobacterium tuberculosis (M. tuberculosis) that infected numerous organ especially the lung. A person’s immunity is very affecting for a person exposed to pulmonary tuberculosis. T-helper-1 cell (Th1) is very influential in the immune system especially in interfering intracellular bacterial infection. One of the cytokines known produced by Th1 cell is interferon gamma (IFN-γ) which is in eliminating M. tuberculosis. The study aims to identify the association between level of IFN-γ and AFB positivity in pulmonary tuberculosis patients in Medan. It is a case-control study. The subjects of the study were 60 new cases of pulmonary tuberculosis with AFB sputum smear- positive that never received ATT consisting 20 cases AFB (+1), 20 cases AFB (+2) and 20 cases AFB (+3).Samples were plasma collected from the venous blood of pulmonary tuberculosis patients. The plasma then underwent laboratory assay with ELISA techniques. Independent t-test was p<0.05 considered significant. Level of IFN-γ in TB AFB (+1) is higher than TB AFB (+2) and (+3), with thesignificant statistical result (p=0.001).

  20. Interferon-gamma response to the treatment of active pulmonary and extra-pulmonary tuberculosis.

    Science.gov (United States)

    Liang, L; Shi, R; Liu, X; Yuan, X; Zheng, S; Zhang, G; Wang, W; Wang, J; England, K; Via, L E; Cai, Y; Goldfeder, L C; Dodd, L E; Barry, C E; Chen, R Y

    2017-10-01

    Interferon-gamma (IFN-γ) release assays (IGRAs) are used to diagnose tuberculosis (TB) but not to measure treatment response. To measure IFN-γ response to active anti-tuberculosis treatment. Patients from the Henan Provincial Chest Hospital, Henan, China, with TB symptoms and/or signs were enrolled into this prospective, observational cohort study and followed for 6 months of treatment, with blood and sputum samples collected at 0, 2, 4, 6, 8, 16 and 24 weeks. The QuantiFERON® TB-Gold assay was run on collected blood samples. Participants received a follow-up telephone call at 24 months to determine relapse status. Of the 152 TB patients enrolled, 135 were eligible for this analysis: 118 pulmonary (PTB) and 17 extra-pulmonary TB (EPTB) patients. IFN-γ levels declined significantly over time among all patients (P = 0.002), with this decline driven by PTB patients (P = 0.001), largely during the initial 8 weeks of treatment (P = 0.019). IFN-γ levels did not change among EPTB patients over time or against baseline culture or drug resistance status. After 6 months of effective anti-tuberculosis treatment, IFN-γ levels decreased significantly in PTB patients, largely over the initial 8 weeks of treatment. IFN-γ concentrations may offer some value for monitoring anti-tuberculosis treatment response among PTB patients.

  1. Production of interferon-gamma by in vivo tumor-sensitized T cells: Association with active antitumor immunity

    International Nuclear Information System (INIS)

    Bursuker, I.; Pearce, M.T.

    1990-01-01

    The state of active immunity to Meth A fibrosarcoma in mice immunized with an admixture of Meth A cells and Propionibacterium acnes is associated with possession by the host of spleen cells capable of producing interferon-gamma (IFN-gamma) upon in vitro restimulation with irradiated tumor cells. The ability of spleen cells from immunized mice to produce IFN-gamma in response to irradiated Meth A cells decays as active antitumor immunity is replaced by a state of immunological memory. The IFN-producing cells are L3T4+Ly2+, cyclophosphamide-sensitive and radiosensitive T cells, as determined by their sensitivity to corresponding monoclonal antibodies and complement. The induction of IFN-gamma production by in vivo tumor-sensitized T cells is tumor specific, in that spleen cells from mice immunized against Meth A fibrosarcoma can produce IFN in response to irradiated Meth A cells but not in response to another syngeneic tumor M109 lung carcinoma

  2. Inhibition of sup 125 I organification and thyroid hormone release by interleukin-1, tumor necrosis factor-alpha, and interferon-gamma in human thyrocytes in suspension culture

    Energy Technology Data Exchange (ETDEWEB)

    Sato, K.; Satoh, T.; Shizume, K.; Ozawa, M.; Han, D.C.; Imamura, H.; Tsushima, T.; Demura, H.; Kanaji, Y.; Ito, Y. (Institute of Clinical Endocrinology, Tokyo (Japan))

    1990-06-01

    To elucidate the mechanism of decreased 131I uptake by the thyroid gland in patients with subacute thyroiditis and painless thyroiditis, human thyroid follicles were cultured with interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF alpha), and/or interferon-gamma (IFN gamma), and the effects of these cytokines on thyroid function were studied in vitro. When human thyrocytes were cultured in RPMI-1640 medium containing 0.5% fetal calf serum and TSH for 5-8 days, the cells incorporated 125I, synthesized de novo (125I)iodotyrosines and (125I)iodothyronines, and secreted (125I)T4 and (125I)T3 into the medium. IL-1 alpha and IL-1 beta inhibited 125I incorporation and (125I)iodothyronine release in a concentration-dependent manner. The minimal inhibitory effect was detected at 10 pg/ml. Electron microscopic examination revealed a marked decrease in lysosome formation in IL-1-treated thyrocytes. TNF alpha and IFN gamma also inhibited thyroid function in a concentration-dependent manner. Furthermore, when thyrocytes were cultured with IL-1, TNF alpha and IFN gamma, these cytokines more than additively inhibited thyroid function. Although the main mechanism of 131I uptake suppression in the thyroid gland in subacute thyroiditis is due to cellular damage and suppression of TSH release, our present findings suggest that IL-1, TNF alpha, and IFN gamma produced in the inflammatory process within the thyroid gland further inhibit iodine incorporation and at least partly account for the decreased 131I uptake by the thyroid gland in destruction-induced hyperthyroidism.

  3. Inhibition of 125I organification and thyroid hormone release by interleukin-1, tumor necrosis factor-alpha, and interferon-gamma in human thyrocytes in suspension culture

    International Nuclear Information System (INIS)

    Sato, K.; Satoh, T.; Shizume, K.; Ozawa, M.; Han, D.C.; Imamura, H.; Tsushima, T.; Demura, H.; Kanaji, Y.; Ito, Y.

    1990-01-01

    To elucidate the mechanism of decreased 131I uptake by the thyroid gland in patients with subacute thyroiditis and painless thyroiditis, human thyroid follicles were cultured with interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF alpha), and/or interferon-gamma (IFN gamma), and the effects of these cytokines on thyroid function were studied in vitro. When human thyrocytes were cultured in RPMI-1640 medium containing 0.5% fetal calf serum and TSH for 5-8 days, the cells incorporated 125I, synthesized de novo [125I]iodotyrosines and [125I]iodothyronines, and secreted [125I]T4 and [125I]T3 into the medium. IL-1 alpha and IL-1 beta inhibited 125I incorporation and [125I]iodothyronine release in a concentration-dependent manner. The minimal inhibitory effect was detected at 10 pg/ml. Electron microscopic examination revealed a marked decrease in lysosome formation in IL-1-treated thyrocytes. TNF alpha and IFN gamma also inhibited thyroid function in a concentration-dependent manner. Furthermore, when thyrocytes were cultured with IL-1, TNF alpha and IFN gamma, these cytokines more than additively inhibited thyroid function. Although the main mechanism of 131I uptake suppression in the thyroid gland in subacute thyroiditis is due to cellular damage and suppression of TSH release, our present findings suggest that IL-1, TNF alpha, and IFN gamma produced in the inflammatory process within the thyroid gland further inhibit iodine incorporation and at least partly account for the decreased 131I uptake by the thyroid gland in destruction-induced hyperthyroidism

  4. Estimation of radiotherapy and MCNU versus radiotherapy and MCNU plus interferon-[beta] for the treatment of anaplastic astrocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Kiya, Katsuzo; Uozumi, Tohru; Kurisu, Kaoru; Ogasawara, Hidenori; Sugiyama, Kazuhiko; Maeda, Hitoshi; Harada, Kunyu (Hiroshima Univ. (Japan). School of Medicine)

    1993-02-01

    The efficacy of radiotherapy and MCNU (MR) was estimated in comparison with radiotherapy and MCNU plus interferon-[beta] (IMR) in 25 patients with anaplastic astrocytoma. The MR group received irradiation with 50[approx]60 Gy and intravenous administration of 2 mg/kg of MCNU on the initial day of irradiation and following every 6[approx]8 weeks interval. The IMR group also received the same regimen in addition to intravenous infusion of 2 x 10[sup 6] IU/m[sup 2] of interferon-[beta] for 5 serial days every eight weeks and following once every two weeks. There were no significant differences between the two groups in terms of background. The response rates of MR and IMR group were 38.5% and 66.7%, respectively. The times to tumor progression (TTP) in the two groups were 11.9[+-]5.8 months and 13.6[+-]7.7 months, respectively. Thus, IMR therapy seems to be more efficacious for patients with anaplastic astrocytoma than MR therapy, but further trials are necessary. (author).

  5. Vitrification of transuranic and beta-gamma contaminated solid wastes

    International Nuclear Information System (INIS)

    Dukes, M.D.

    1980-06-01

    Vitrification of solid transuranic contaminated (TRU) wastes alone and with high-level liquid wastes (HLLW) was studied. Homogeneous glasses containing 20 to 30 wt % ash were made by using glass frits previously developed at the Savannah River Plant and Pacific Northwest Laboratories. If the ash is vitrified along with the HLLW, 1.0 wt % as can be added to the waste forms without affecting their quality. This loading of ash is well above the loading required by the relative amounts of HLLW and TRU ash that will be processed at the Savannah River Plant. Vitrification of TRU-contaminated electropolishing sludges and high efficiency particular air filter materials along with HLLW would require an increase in the quantity of glass to be produced. However, if these TRU-contaminated solids were vitrified with the HLLW, the addition of low-level beta-gamma contaminated ash would require no further increase in glass production

  6. Perturbed beta-gamma systems and complex geometry

    Energy Technology Data Exchange (ETDEWEB)

    Zeitlin, Anton M. [Department of Mathematics, Yale University, 442 Dunham Lab, 10 Hillhouse Avenue, New Haven, CT 06511 (United States)], E-mail: anton.zeitlin@yale.edu

    2008-05-11

    We consider the equations, arising as the conformal invariance conditions of the perturbed curved beta-gamma system. These equations have the physical meaning of Einstein equations with a B-field and a dilaton on a Hermitian manifold, where the B-field 2-form is imaginary and proportional to the canonical form associated with Hermitian metric. We show that they decompose into linear and bilinear equations and lead to the vanishing of the first Chern class of the manifold where the system is defined. We discuss the relation of these equations to the generalized Maurer-Cartan structures related to BRST operator. Finally we describe the relations of the generalized Maurer-Cartan bilinear operation and the Courant/Dorfman brackets.

  7. Modeling dynamic beta-gamma polymorphic transition in Tin

    Science.gov (United States)

    Chauvin, Camille; Montheillet, Frank; Petit, Jacques; CEA Gramat Collaboration; EMSE Collaboration

    2015-06-01

    Solid-solid phase transitions in metals have been studied by shock waves techniques for many decades. Recent experiments have investigated the transition during isentropic compression experiments and shock-wave compression and have highlighted the strong influence of the loading rate on the transition. Complementary data obtained with velocity and temperature measurements around the polymorphic transition beta-gamma of Tin on gas gun experiments have displayed the importance of the kinetics of the transition. But, even though this phenomenon is known, modeling the kinetic remains complex and based on empirical formulations. A multiphase EOS is available in our 1D Lagrangian code Unidim. We propose to present the influence of various kinetic laws (either empirical or involving nucleation and growth mechanisms) and their parameters (Gibbs free energy, temperature, pressure) on the transformation rate. We compare experimental and calculated velocities and temperature profiles and we underline the effects of the empirical parameters of these models.

  8. MicroRNA Expression Changes during Interferon-Beta Treatment in the Peripheral Blood of Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    Georg Füllen

    2013-08-01

    Full Text Available MicroRNAs (miRNAs are small non-coding RNA molecules acting as post-transcriptional regulators of gene expression. They are involved in many biological processes, and their dysregulation is implicated in various diseases, including multiple sclerosis (MS. Interferon-beta (IFN-beta is widely used as a first-line immunomodulatory treatment of MS patients. Here, we present the first longitudinal study on the miRNA expression changes in response to IFN-beta therapy. Peripheral blood mononuclear cells (PBMC were obtained before treatment initiation as well as after two days, four days, and one month, from patients with clinically isolated syndrome (CIS and patients with relapsing-remitting MS (RRMS. We measured the expression of 651 mature miRNAs and about 19,000 mRNAs in parallel using real-time PCR arrays and Affymetrix microarrays. We observed that the up-regulation of IFN-beta-responsive genes is accompanied by a down-regulation of several miRNAs, including members of the mir-29 family. These differentially expressed miRNAs were found to be associated with apoptotic processes and IFN feedback loops. A network of miRNA-mRNA target interactions was constructed by integrating the information from different databases. Our results suggest that miRNA-mediated regulation plays an important role in the mechanisms of action of IFN-beta, not only in the treatment of MS but also in normal immune responses. miRNA expression levels in the blood may serve as a biomarker of the biological effects of IFN-beta therapy that may predict individual disease activity and progression.

  9. Standardization of low energy beta and beta-gamma complex emitters by the tracer and the efficiency extrapolation methods

    International Nuclear Information System (INIS)

    Sahagia, M.

    1978-01-01

    The absolute standardization of radioactive solutions of low energy beta emitters and beta-gamma emitters with a high probability of disintegration to the ground state is described; the tracer and the efficiency extrapolation methods were used. Both types of radionuclides were mathematically and physically treated in an unified manner. The theoretical relations between different beta spectra were calculated according to Williams' model and experimentally verified for: 35 S + 60 Co, 35 S + 95 Nb, 147 Pm + 60 Co, 14 C + 95 Nb and two beta branches of 99 Mo. The optimum range of beta efficiency variation was indicated. The basic supposition that all beta efficieny tend to unity in the same time was experimentally verified, using two 192 Ir beta branches. Four computer programs, written in the FORTRAN IV language, were elaborated, for the adequate processing of the experimental data. Good precision coefficients according to international standards were obtained in the absolute standardization of 35 S, 147 Pm, 99 Mo solutions. (author)

  10. Effects of interferon gamma and specific polyclonal antibody on the infection of murine peritoneal macrophages and murine macrophage cell line PMJ2-R with Encephalitozoon cuniculi

    Czech Academy of Sciences Publication Activity Database

    Jelínek, Jiří; Salát, Jiří; Sak, Bohumil; Kopecký, Jan

    2007-01-01

    Roč. 54, č. 3 (2007), s. 172-176 ISSN 0015-5683 R&D Projects: GA ČR GP524/03/D167 Institutional research plan: CEZ:AV0Z60220518 Keywords : microsporidia * Encephalitozoon cuniculi * antibody * macrophage s * interferon gamma (IFN-gamma) Subject RIV: EC - Immunology Impact factor: 1.000, year: 2007

  11. Comparison of histopathology, cultivation of tissues and rectal contents, and interferon-gamma and serum antibody responses for the diagnosis of bovine paratuberculosis

    DEFF Research Database (Denmark)

    Huda, A.; Jensen, H.E.

    2003-01-01

    contents, and (3) examination of repeated blood samples for interferon-gamma (IFN-gamma) and antibody responses. Tissue samples were taken from the small and large intestine and corresponding mesenteric lymph nodes, and from the pharyngeal tonsil and other lymphoid nodes (retropharyngeal, mediastinal...

  12. Molecular characterization and development of Sarcocystis speeri sarcocysts in gamma interferon gene knockout mice.

    Science.gov (United States)

    Dubey, J P; Verma, S K; Dunams, D; Calero-Bernal, R; Rosenthal, B M

    2015-11-01

    The North American opossum (Didelphis virginiana) is the definitive host for at least three named species of Sarcocystis: Sarcocystis falcatula, Sarcocystis neurona and Sarcocystis speeri. The South American opossums (Didelphis albiventris, Didelphis marsupialis and Didelphis aurita) are definitive hosts for S. falcatula and S. lindsayi. The sporocysts of these Sarcocystis species are similar morphologically. They are also not easily distinguished genetically because of the difficulties of DNA extraction from sporocysts and availability of distinguishing genetic markers. Some of these species can be distinguished by bioassay; S. neurona and S. speeri are infective to gamma interferon gene knockout (KO) mice, but not to budgerigars (Melopsittacus undulatus); whereas S. falcatula and S. lindsayi are infective to budgerigars but not to KO mice. The natural intermediate host of S. speeri is unknown. In the present study, development of sarcocysts of S. speeri in the KO mice is described. Sarcocysts were first seen at 12 days post-inoculation (p.i.), and they became macroscopic (up to 4 mm long) by 25 days p.i. The structure of the sarcocyst wall did not change from the time bradyzoites had formed at 50-220 days p.i. Sarcocysts contained unique villar protrusions, 'type 38'. The polymerase chain reaction amplifications and sequences analysis of three nuclear loci (18S rRNA, 28S rRNA and ITS1) and two mitochondrial loci (cox1 and cytb) of S. speeri isolate from an Argentinean opossum (D. albiventris) confirmed its membership among species of Sarcocystis and indicated an especially close relationship to another parasite in this genus that employs opossums as its definitive host, S. neurona. These results should be useful in finding natural intermediate host of S. speeri.

  13. Household food insecurity is associated with low interferon-gamma levels in pregnant Indian women.

    Science.gov (United States)

    Vaidya, A; Bhosale, R; Sambarey, P; Suryavanshi, N; Young, S; Mave, V; Kanade, S; Kulkarni, V; Deshpande, P; Balasubramanian, U; Elf, J; Gupte, N; Gupta, A; Mathad, J S

    2017-07-01

    Over 20% of tuberculosis (TB) cases during pregnancy occur in India. To determine the association between household food insecurity and interferon-gamma (IFN-γ) levels in pregnancy. Pregnant women in India were administered the Household Food Insecurity Access Scale (HFIAS) questionnaire and underwent an IFN-γ release assay. Logistic regression was used to identify factors associated with food insecurity. Of 538 women, 60 (11%) had household food insecurity, 47 (78%) of which were moderate or severe food insecure. After mitogen stimulation, moderate or severe food insecure women had a median IFN-γ concentration of 4.2 IU/ml (IQR 2.2-9.8) vs. 8.4 IU/ml (IQR 3.0-10) in women with no or mild food insecurity (P = 0.03). In multivariate analysis, higher IFN-γ concentrations were associated with human immunodeficiency virus infection (OR 1.3, 95%CI 0.51-2.1, P = 0.001), and inversely associated with moderate or severe food insecurity (OR -1.6, 95%CI -2.9 to -0.27, P = 0.02) and the number of adults in the household (OR -0.08, 95%CI -0.16 to -0.01, P = 0.03). There was no association between food insecurity and IFN-γ response to Mycobacterium tuberculosis antigen. Food insecurity in pregnancy is associated with low IFN-γ levels. There was no association between food insecurity and IFN-γ response to M. tuberculosis antigen, but our study was underpowered to detect this outcome.

  14. Secretion of interferon gamma from human immune cells is altered by exposure to tributyltin and dibutyltin.

    Science.gov (United States)

    Lawrence, Shanieek; Reid, Jacqueline; Whalen, Margaret

    2015-05-01

    Tributyltin (TBT) and dibutyltin (DBT) are widespread environmental contaminants found in food, beverages, and human blood samples. Both of these butyltins (BTs) interfere with the ability of human natural killer (NK) cells to lyse target cells and alter secretion of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) from human immune cells in vitro. The capacity of BTs to interfere with secretion of other pro-inflammatory cytokines has not been examined. Interferon gamma (IFNγ) is a modulator of adaptive and innate immune responses, playing an important role in overall immune competence. This study shows that both TBT and DBT alter secretion of IFNγ from human immune cells. Peripheral blood cell preparations that were increasingly reconstituted were used to determine if exposures to either TBT or DBT affected IFNγ secretion and how the makeup of the cell preparation influenced that effect. IFNγ secretion was examined after 24 h, 48 h, and 6 day exposures to TBT (200 - 2.5 nM) and DBT (5 - 0.05 µM) in highly enriched human NK cells, a monocyte-depleted preparation of PBMCs, and monocyte-containing PBMCs. Both BTs altered IFNγ secretion from immune cells at most of the conditions tested (either increasing or decreasing secretion). However, there was significant variability among donors as to the concentrations and time points that showed changes as well as the baseline secretion of IFNγ. The majority of donors showed an increase in IFNγ secretion in response to at least one concentration of TBT or DBT at a minimum of one length of exposure. © 2013 Wiley Periodicals, Inc.

  15. Is TB Testing Associated With Increased Blood Interferon-Gamma Levels?

    Directory of Open Access Journals (Sweden)

    Aideen E. Kennedy

    2017-10-01

    Full Text Available The Republic of Ireland reports a relatively low prevalence of Johne’s disease (JD compared to international counterparts. Postulated reasons for this include a lower average herd size and a grass-based production system. Ireland also engages in high levels of bovine tuberculosis (bTB testing. As interferon-gamma (IFN-γ is believed to play a key role in protecting against JD, it is our hypothesis that administration of purified protein derivative (PPD, as part of the bTB test, is associated with a systemic increase in IFN-γ production, which may potentially limit clinical progression of the disease. We studied 265 cows (202 Friesian and 63 “Non-Friesian,” e.g., JerseyX, Norwegian Red to assess IFN-γ levels and Mycobacterium avium subspecies paratuberculosis (MAP antibody response before and after the bTB test. As part of the compulsory annual bTB test, avian and bovine PPD were administered at two separate cervical sites. To assess IFN-γ production, blood samples were taken before and 72 h after PPD administration. MAP antibody response was assessed before and 10 days post-PPD administration. A significant increase in MAP antibody response was identified post-bTB compared to pre-bTB response (p < 0.001. Additionally, IFN-γ production significantly increased at the post-bTB time point (p < 0.001 compared to the pre-bTB test readings. This may indicate a beneficial effect of bTB testing in controlling JD.

  16. Interferon-gamma inducible protein-10 as a potential biomarker in localized scleroderma

    Science.gov (United States)

    2013-01-01

    Introduction The purpose of this study was to evaluate the presence and levels of interferon-gamma inducible protein-10 (IP-10) in the plasma and skin of pediatric localized scleroderma (LS) patients compared to those of healthy pediatric controls and to determine if IP-10 levels correlate to clinical disease activity measures. Methods The presence of IP-10 in the plasma was analyzed using a Luminex panel in 69 pediatric patients with LS and compared to 71 healthy pediatric controls. Of these patients, five had available skin biopsy specimens with concurrent clinical and serological data during the active disease phase, which were used to analyze the presence and location of IP-10 in the skin by immunohistochemistry (IHC). Results IP-10 levels were significantly elevated in the plasma of LS patients compared to that of healthy controls and correlated to clinical disease activity measures in LS. Immunohistochemistry staining of IP-10 was present in the dermal infiltrate of LS patients and was similar to that found in psoriasis skin specimens, the positive disease control. Conclusions Elevation of IP-10 levels in the plasma compared to those of healthy controls and the presence of IP-10 staining in the affected skin of LS patients indicates that IP-10 is a potential biomarker in LS. Furthermore, significant elevation of IP-10 in LS patients with active versus inactive disease and correlations between IP-10 levels and standardized disease outcome measures of activity in LS strongly suggest that IP-10 may be a biomarker for disease activity in LS. PMID:24499523

  17. Frequency of indeterminate results from an interferon-gamma release assay among HIV-infected individuals

    Directory of Open Access Journals (Sweden)

    Sandra Maria do Valle Leone de Oliveira

    Full Text Available ABSTRACT Objective: To evaluate the frequency of and factors associated with indeterminate interferon-gamma release assay (IGRA results in people living with HIV/AIDS (PLWHA. Methods: We tested 81 PLWHA in the central-west region of Brazil, using the tuberculin skin test and an IGRA. Information on sociodemographic and clinical variables was gathered through the use of questionnaires and from medical records. The association of those variables with indeterminate results was analyzed by calculating the adjusted ORs in a multivariate logistic regression model. Concordance was evaluated by determining the kappa statistic. Results: Among the 81 patients evaluated, the tuberculin skin test results were positive in 18 (22.2% of the patients, and the IGRA results were positive in 10 (12.3%, with a kappa of 0.62. The IGRA results were indeterminate in 22 (27.1% of the patients (95% CI: 17.8-38.1%. The odds of obtaining indeterminate results were significantly higher in smokers (adjusted OR = 6.0; 95% CI: 1.4-26.7 and in samples stored for less than 35 days (adjusted OR = 14.0; 95% CI: 3.1-64.2. Patients with advanced immunosuppression (CD4+ T-cell count < 200 cells/mm3 were at a higher risk for indeterminate results (OR adjusted for smoking and inadequate duration of sample storage = 4.7; 95% CI: 0.91-24.0, although the difference was not significant. Conclusions: The high prevalence of indeterminate results can be a major limitation for the routine use of IGRAs in PLWHA. The need to repeat the test increases its costs and should be taken into account in cost-effectiveness studies. The processing of samples can significantly alter the results.

  18. Interferon-gamma and interleukin-10 profile of children with tuberculosis in North Sumatera, Indonesia

    Science.gov (United States)

    Daulay, R. S.; Daulay, R. M.

    2018-03-01

    Cellular immunity was mediated the host immune response against Mycobacterium tuberculosis, in which cytokine and T-helper (Th) 1 cells play an important role. Interferon-gamma (IFN-γ) is a leading cytokine involved in the immune response of tuberculosis (TB).The primary function of IFN-γ is to activate macrophages in opposition Mycobacterium tuberculosis. Contrast from IFN-γ, interleukin-10 (IL-10) is considered inhibitory cytokine, important to an adequate balance between inflammatory responses. To analyze cytokine profile, particularly IFN-γ and IL-10 of the children with TB in Indonesia, a cross-sectional study was conducted at two general hospitals and seven primary health care located in Medan and Batubara, North Sumatera, Indonesia. Among 51 children with TB disease and 51 healthy children, found that IFN-γ and IL-10 levels were lower in TB patients compared to healthy children. Statistically significant decreased production of the IFN-γ levels (p=0.042) were found in TB patients 9.41 (1.10-28.06) pg/ml contrast to healthy children 6.30 (1.30-89.76) pg/ml. Homologue finding of the IL-10 levels were also found in TB patients 4.93 (0.22-48.01) pg/ml and 4.93 (0.07-81.60) pg/ml in healthy children, but not statistically significant (p=0.784). High levels of IL-10 were not proven to suppress the levels production of IFN-γ in TB patients.

  19. Functional polymorphisms of interferon-gamma affect pneumonia-induced sepsis.

    Directory of Open Access Journals (Sweden)

    Ding Wang

    Full Text Available Sepsis is an inflammatory syndrome caused by infection, and both its incidence and mortality are high. Because interferon-gamma (IFN-γ plays an important role in inflammation, this work assessed IFN-γ single nucleotide polymorphism (SNPs that may be associated with sepsis.A total of 196 patients with pneumonia-induced sepsis and 213 age- and sex-matched healthy volunteers participated in our study from July 2012 to July 2013 in Guangzhou, China. Patient clinical information was collected. Clinical pathology was assessed in subgroups defined based on clinical criteria, APACHE II (acute physiology and chronic health evaluation and SOFA (sepsis-related organ failure assessment scores and discharge rate. Four functional SNPs, -1616T/C (rs2069705, -764G/C (rs2069707, +874A/T (rs2430561 and +3234C/T (rs2069718, were genotyped by Snapshot in both sepsis patients and healthy controls. Pearson's chi-square test or Fisher's exact test were used to analyze the distribution of the SNPs, and the probability values (P values, odds ratios (OR and 95% confidence intervals (CIs were calculated.No mutations in the IFN-γ -764G/C SNP were detected among the participants in our study. The +874A/T and +3234C/T SNPs were in strong linkage disequilibrium (LD (r(2 = 0.894. The -1616 TC+TT, +874 AT+AA genotype and the TAC haplotype were significantly associated with sepsis susceptibility, while the CTT haplotype was associated with protection against sepsis incidence. Genotype of -1616 TT wasn't only protective against severity of sepsis, but also against higher APACHE II and SOFA scores as +874 AA and +3234 CC. The TAC haplotype was was protective against progression to severe sepsis either.Our results suggest that functional IFN-γ SNPs and their haplotypes are associated with pneumonia-induced sepsis.

  20. Using support vector machine to predict beta- and gamma-turns in proteins.

    Science.gov (United States)

    Hu, Xiuzhen; Li, Qianzhong

    2008-09-01

    By using the composite vector with increment of diversity, position conservation scoring function, and predictive secondary structures to express the information of sequence, a support vector machine (SVM) algorithm for predicting beta- and gamma-turns in the proteins is proposed. The 426 and 320 nonhomologous protein chains described by Guruprasad and Rajkumar (Guruprasad and Rajkumar J. Biosci 2000, 25,143) are used for training and testing the predictive model of the beta- and gamma-turns, respectively. The overall prediction accuracy and the Matthews correlation coefficient in 7-fold cross-validation are 79.8% and 0.47, respectively, for the beta-turns. The overall prediction accuracy in 5-fold cross-validation is 61.0% for the gamma-turns. These results are significantly higher than the other algorithms in the prediction of beta- and gamma-turns using the same datasets. In addition, the 547 and 823 nonhomologous protein chains described by Fuchs and Alix (Fuchs and Alix Proteins: Struct Funct Bioinform 2005, 59, 828) are used for training and testing the predictive model of the beta- and gamma-turns, and better results are obtained. This algorithm may be helpful to improve the performance of protein turns' prediction. To ensure the ability of the SVM method to correctly classify beta-turn and non-beta-turn (gamma-turn and non-gamma-turn), the receiver operating characteristic threshold independent measure curves are provided. (c) 2008 Wiley Periodicals, Inc.

  1. An Albumin-Free Formulation for Escherichia coli-Derived Interferon Beta-1b with Decreased Immunogenicity in Immune Tolerant Mice

    NARCIS (Netherlands)

    Haji Abdolvahab, Mohadeseh; Fazeli, Ahmad; Radmalekshahi, Mazda; Nejadnik, M Reza; Fazeli, Mohammad Reza; Schellekens, Huub

    2016-01-01

    Human serum albumin (HSA)-free formulation of Escherichia coli-derived human interferon beta (IFNβ-1b) with a high percentage of monomeric protein and low immunogenicity is developed and characterized in the current study. UV spectroscopy, fluorescence spectroscopy, dynamic light scattering, sodium

  2. CaSO4: Dy + Teflon dosimetric pellets for X, beta and gamma radiation detection

    International Nuclear Information System (INIS)

    Campos, L.L.; Lima, M.F.

    1987-08-01

    CaSO 4 : Dy + TEFLON dosimetric pellets with high sensitivity and low cost for X, beta and gamma radiation monitoring were studied and developed by the Dosimetric Material Production Laboratory of the Radiological Protection Departament and are disposable for sale. The thickness of the pellets are suitable for X, beta and gamma radiation measurements. The dosimetric properties of these pellets were determined and presented in this work. The results show the usefulness of 0,20mm thick pellets for beta radiation monitoring and 0,80mm thick pellets for x and gamma radiation detection. (Author) [pt

  3. Clinical practice of analysis of anti-drug antibodies against interferon beta and natalizumab in multiple sclerosis patients in Europe

    DEFF Research Database (Denmark)

    Link, Jenny; Ramanujam, Ryan; Auer, Michael

    2017-01-01

    Antibodies against biopharmaceuticals (anti-drug antibodies, ADA) have been a well-integrated part of the clinical care of multiple sclerosis (MS) in several European countries. ADA data generated in Europe during the more than 10 years of ADA monitoring in MS patients treated with interferon beta...... positive test. Shorter times were observed for IFNβ-1b-Extavia s.c. (0.99 and 0.94 years) and natalizumab (0.25 and 0.23 years), which were introduced on the market when ADA testing was already available, as compared to IFNβ-1a i.m. (1.41 and 2.27 years), IFNβ-1b-Betaferon s.c. (2.51 and 1.96 years...

  4. Microcalorimetric and spectrographic studies on host-guest interactions of {alpha}-, {beta}-, {gamma}- and M{beta}-cyclodextrin with resveratrol

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hui; Xu, Xiangyu; Liu, Min [College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, Shandong Province (China); Sun, Dezhi, E-mail: sundezhisdz@163.com [College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, Shandong Province (China); Li, Linwei, E-mail: lilinwei@lcu.edu.cn [College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, Shandong Province (China)

    2010-10-20

    Thermal effects of inclusion processes of {alpha}-, {beta}-, {gamma}- and M{beta}-cyclodextrin with resveratrol (RES) in aqueous solutions were determined by isothermal titration calorimetry (ITC) with nanowatt sensitivity at the temperature of 298.15 K. Standard enthalpy changes, stoichiometry and equilibrium constants of the inclusion complexes were derived from the direct calorimetric data utilizing nonlinear simulation. The thermodynamic parameters were discussed in the light of weak interactions between the host and the guest molecules combining with UV spectral message. The results indicate that all of the complexes formed in the aqueous solutions are in 1:1 stoichiometry. The binding processes of {alpha}-, {beta}- and M{beta}-cyclodextrin with the guest are mainly driven by enthalpy, while that of {gamma}-cyclodextrin with the drug is driven by both enthalpy and entropy.

  5. Growth hormone, interferon-gamma, and leukemia inhibitory factor utilize insulin receptor substrate-2 in intracellular signaling

    DEFF Research Database (Denmark)

    Argetsinger, L S; Norstedt, G; Billestrup, Nils

    1996-01-01

    In this report, we demonstrate that insulin receptor substrate-2 (IRS-2) is tyrosyl-phosphorylated following stimulation of 3T3-F442A fibroblasts with growth hormone (GH), leukemia inhibitory factor and interferon-gamma. In response to GH and leukemia inhibitory factor, IRS-2 is immediately...... for GH is further demonstrated by the finding that GH stimulates association of IRS-2 with the 85-kDa regulatory subunit of phosphatidylinositol 3'-kinase and with the protein-tyrosine phosphatase SHP2. These results are consistent with the possibility that IRS-2 is a downstream signaling partner...

  6. Interferon-beta for relapsing-remitting multiple sclerosis: a systematic review

    Directory of Open Access Journals (Sweden)

    Dian HE

    2014-09-01

    Full Text Available Objective To assess the efficacy and safety of interferon-beta (IFN-β as monotherapy versus placebo for patients with relapsing-remitting multiple sclerosis (RRMS.  Methods We searched Cochrane Central Register of Controlled Trials (CENTRAL, PubMed, EMBASE, CINAHL, LILACS, PEDRO, China Biology Medicine Disc (CBMDisc, as well as clinical trial registries and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP, retrieval deadline: June 2014. Furthermore, we checked reference lists of published reviews and retrieved articles, and communicated personally with investigators and biotechnology companies participating in trials of IFN-β in an effort to identify further studies or unpublished data. Two review authors independently screened studies, extracted data and evaluated the risk of bias. Formal Meta-analysis were conducted by using Review Manager software (Version 5.3.3 and the impacts of limitations in study design or execution (risk of bias, inconsistency in results, imprecision of results, indirectness of evidence and publication bias on the quality of the body of evidence were assessed.  Results A total of 576 articles were retrieved. After screening of titles and abstracts, 26 studies were provisionally selected. The full text of papers were obtained for further assessment of eligibility. Finally, 5 studies were included, involving 2129 patients with RRMS (high-dose IFN-β group: N = 1076; placebo group: N = 1053. All studies were randomized, double-blind, controlled, parallel-group clinical trials with a follow-up for at least one year, evaluating IFN-β versus placebo as monotherapy for patients with RRMS. Most studies had methodological limitations, mainly on a high risk of attrition bias. Moreover, the intention to treat (ITT principle was not used in data analysis. Data from only 919 patients (43.17% were available to calculate the primary outcomes at 2 years of follow-up. Meta-analysis indicated

  7. Rearrangement of beta,gamma-unsaturated esters with thallium trinitrate: synthesis of indans bearing a beta-keto ester moiety

    Directory of Open Access Journals (Sweden)

    Silva Jr. Luiz F.

    2006-01-01

    Full Text Available The rearrangement of beta,gamma-unsaturated esters, such as 2-(3,4-dihydronaphthalen-1-yl-propionic acid ethyl ester, with thallium trinitrate (TTN in acetic acid leads to 3-indan-1-yl-2-methyl-3-oxo-propionic acid ethyl ester in good yield, through a ring contraction reaction. The new indans thus obtained feature a beta-keto ester moiety, which would be useful for further functionalization.

  8. Analysis of radionuclide mixtures by {alpha}-{gamma} and {beta}-{gamma} coincidences using a simple device; Analyse de melanges de radionucleides par un dispositif simple de coincidences {alpha}-{gamma} et {beta}-{gamma}

    Energy Technology Data Exchange (ETDEWEB)

    Pottier, R; Berger, R [Commissariat a l' Energie Atomique, Centre d' Etudes Nucleaires de Fontenay-aux-Roses, 92 (France)

    1966-06-01

    A procedure is described for the qualitative and quantitative spectrographic analysis of radioactive sources containing two alpha-gamma emitters having the same alpha energy or two beta-gamma emitters having the same gamma energy. The main apparatus is a multichannel pulse-height analyzer including a coincidence circuit. The principle of the method, the synoptic scheme, the electronic device, the type of sources, and the precautions to be taken or the corrections to take into account are reported. The results obtained in solving the three following problems are discussed as examples of applications of the method: analysis of {sup 241}Am in alpha-gamma sources containing {sup 238}Pu; analysis of {sup 237}Np in beta-gamma sources containing {sup 239}Pu; and analysis of {sup 106}Ru-{sup 106}Rh in beta-gamma sources containing {sup 95}Zr-{sup 95}Nb. (authors) [French] Dans ce. rapport, on presente une methode d'analyse spectrographique qualitative et quantitative de sources radioactives contenant deux emetteurs alpha-gamma de meme energie alpha et deux emetteurs beta-gamma de meme energie gamma. L'organe principal est un analyseur d'amplitude a 400 canaux comprenant un circuit de coincidence. On decrit le principe de la methode, le schema synoptique, l'appareillage, le type des sources, les precautions a prendre ou les corrections a faire. On discute les resultats obtenus dans la solution des trois problemes suivants traites a titre d'application de la methode: 1. analyse d'americium 241 en presence de plutonium 238; 2. analyse de neptunium 237 en presence de plutonium 239; 3. analyse de ruthenium 106-rhodium 106 en presence de zirconium 95-niobium 95. (auteurs)

  9. A new extremity dosemeter for beta and gamma radiation

    International Nuclear Information System (INIS)

    Heinzelmann, M.; Pagenkamper, M.

    1988-01-01

    An extremity dosemeter developed at the Juelich Nuclear Research Centre is very well suited for the precise and energy-independent measurement of the skin dose generated by beta or gamma radiation. This is also confirmed by the results of this intercomparison programme. The dosemeter contains three TLDs of LiF in Teflon mounted behind a window of 0.9 mg/cm 2 . The great advantage of this dosemeter is three TLD's enabling statements about the radiation quality. However, the dosemeter has two disadvantages The dosemeter is complicated to manufacture. A very thin plastic foil of 0.9 mg/cm 2 must be attached to a support. This work is difficult and time-consuming and cannot be automated. The window in front of the TLD is not sturdy enough and is occasionally destroyed when the dosemeter is being worn. These two disadvantages prevent this extremity dosemeter from being used more frequently. For this reason, work was begun on developing a new extremity dosemeter without these two disadvantages. The great advantage of the previous dosemeter of obtaining statements about the type of radiation with the aid of readings from three TLD's was to be retained. The improved extremity dosemeter has a more sturdy and thicker window with a similar response as the previous dosemeter with a thinner window

  10. Beta and gamma dose calculations for PWR and BWR containments

    International Nuclear Information System (INIS)

    King, D.B.

    1989-07-01

    Analyses of gamma and beta dose in selected regions in PWR and BWR containment buildings have been performed for a range of fission product releases from selected severe accidents. The objective of this study was to determine the radiation dose that safety-related equipment could experience during the selected severe accident sequences. The resulting dose calculations demonstrate the extent to which design basis accident qualified equipment could also be qualified for the severe accident environments. Surry was chosen as the representative PWR plant while Peach Bottom was selected to represent BWRs. Battelle Columbus Laboratory performed the source term release analyses. The AB epsilon scenario (an intermediate to large LOCA with failure to recover onsite or offsite electrical power) was selected as the base case Surry accident, and the AE scenario (a large break LOCA with one initiating event and a combination of failures in two emergency cooling systems) was selected as the base case Peach Bottom accident. Radionuclide release was bounded for both scenarios by including spray operation and arrested sequences as variations of the base scenarios. Sandia National Laboratories used the source terms to calculate dose to selected containment regions. Scenarios with sprays operational resulted in a total dose comparable to that (2.20 x 10 8 rads) used in current equipment qualification testing. The base case scenarios resulted in some calculated doses roughly an order of magnitude above the current 2.20 x 10 8 rad equipment qualification test region. 8 refs., 23 figs., 12 tabs

  11. Alpha/beta(gamma ray) discrimination and spillover quantification with a BaF2 scintillator

    International Nuclear Information System (INIS)

    DeVol, T.A.; Fjeld, R.A.

    1994-01-01

    A simple pulse shape discrimination technique was used to separate alpha and beta(gamma ray) interactions in a BaF 2 scintillator. The separation was not ideal, resulting in a 5.1% spillover of alpha interactions into the beta(gamma ray) channel and 11.9% spillover of beta(gamma ray) interactions into the alpha channel for a set pulse shape discriminator. The misclassification of events was reduced by post-processing the data using either a simple analytical technique or a more complex linear least squares technique. Both techniques typically reduced the difference between the expected and calculated interaction rates to <10% when the ratio of beta(gamma ray) to alpha count rate was less than 100 : 1. ((orig.))

  12. Reproducibility of Interferon Gamma (IFN-γ) Release Assays. A Systematic Review

    Science.gov (United States)

    Tagmouti, Saloua; Slater, Madeline; Benedetti, Andrea; Kik, Sandra V.; Banaei, Niaz; Cattamanchi, Adithya; Metcalfe, John; Dowdy, David; van Zyl Smit, Richard; Dendukuri, Nandini

    2014-01-01

    Rationale: Interferon gamma (IFN-γ) release assays for latent tuberculosis infection result in a larger-than-expected number of conversions and reversions in occupational screening programs, and reproducibility of test results is a concern. Objectives: Knowledge of the relative contribution and extent of the individual sources of variability (immunological, preanalytical, or analytical) could help optimize testing protocols. Methods: We performed a systematic review of studies published by October 2013 on all potential sources of variability of commercial IFN-γ release assays (QuantiFERON-TB Gold In-Tube and T-SPOT.TB). The included studies assessed test variability under identical conditions and under different conditions (the latter both overall and stratified by individual sources of variability). Linear mixed effects models were used to estimate within-subject SD. Measurements and Main Results: We identified a total of 26 articles, including 7 studies analyzing variability under the same conditions, 10 studies analyzing variability with repeat testing over time under different conditions, and 19 studies reporting individual sources of variability. Most data were on QuantiFERON (only three studies on T-SPOT.TB). A considerable number of conversions and reversions were seen around the manufacturer-recommended cut-point. The estimated range of variability of IFN-γ response in QuantiFERON under identical conditions was ±0.47 IU/ml (coefficient of variation, 13%) and ±0.26 IU/ml (30%) for individuals with an initial IFN-γ response in the borderline range (0.25–0.80 IU/ml). The estimated range of variability in noncontrolled settings was substantially larger (±1.4 IU/ml; 60%). Blood volume inoculated into QuantiFERON tubes and preanalytic delay were identified as key sources of variability. Conclusions: This systematic review shows substantial variability with repeat IFN-γ release assays testing even under identical conditions, suggesting that reversions

  13. Delayed growth of EL4 lymphoma in SR-A-deficient mice is due to upregulation of nitric oxide and interferon-gamma production by tumor-associated macrophages.

    Science.gov (United States)

    Komohara, Yoshihiro; Takemura, Kenichi; Lei, Xiao Feng; Sakashita, Naomi; Harada, Mamoru; Suzuki, Hiroshi; Kodama, Tatsuhiko; Takeya, Motohiro

    2009-11-01

    Class A scavenger receptors (SR-A, CD204) are highly expressed in tumor-associated macrophages (TAM). To investigate the function of SR-A in TAM, wild-type and SR-A-deficient (SR-A(-/-)) mice were injected with EL4 cells. Although these groups of mice did not differ in the numbers of infiltrating macrophages and lymphocytes and in neovascularization, SR-A(-/-) mice had delayed growth of EL4 tumors. Expression of inducible nitric oxide (NO) synthase and interferon (IFN)-gamma mRNA increased significantly in tumor tissues from SR-A(-/-) mice. Engulfment of necrotic EL4 cells induced upregulation of NO and IFN-gamma production by cultured macrophages, and production of NO and IFN-gamma increased in SR-A(-/-) macrophages in vitro. IFN-beta production by cultured macrophages was also elevated in SR-A(-/-) macrophages in vitro. These results suggested that the antitumor activity of macrophages increased in SR-A(-/-) mice because of upregulation of NO and IFN-gamma production. These data indicate an important role of SR-A in regulating TAM function by inhibiting toll-like receptor (TLR)4-IFN-beta signaling.

  14. Role of interferon-gamma in the pathogenesis of LCMV-induced meningitis: unimpaired leucocyte recruitment, but deficient macrophage activation in interferon-gamma knock-out mice

    DEFF Research Database (Denmark)

    Nansen, A; Christensen, Jan Pravsgaard; Röpke, C

    1998-01-01

    , a viral peptide could also elicit a T cell mediated inflammatory response in virus-primed IFN-gamma knock-out mice, indicating that redundancy of this cytokine as a proinflammatory mediator is not restricted to inflammatory reactions triggered by an active infection. Thus, T cell mediated inflammation may...

  15. Comparison of Tuberculin Skin Test result and interferon gamma response to human PPD in BCG scar positive and negative children.

    Science.gov (United States)

    Sayyahfar, Shirin; Karimi, Abdollah; Fahimzad, Alireza; Shamshiri, Ahmad Reza

    2014-03-01

    The aim of this study is to compare Tuberculin Skin Test (TST) result and interferon gamma response to human PPD (purified protein derivative), in scar positive and scar negative BCG-vaccinated children. Between August 2007 and May 2008 a total of 236 children aged 1-168 months (mean 21 months) admitted to Mofid Children's Hospital, Tehran, Iran, were enrolled in a cross-sectional study. Each patient was examined for BCG vaccine scar and tested with TST and human PPD-based Interferon Gamma Release Assay (IGRA). Two hundred and twenty one cases out of 236 (44% female, 1-168 months, mean age 21 months) were scar positive of whom 95% TST result was negative. Human PPD-based IGRA was positive in 110 (49.8%), negative in 85 (38.4 %) and indeterminate in 26 (11.8%) of scar positive patients. Fifteen children (40% female, 1-156 months; mean age 42 months) were scar negative. All the scar negative cases were TST negative. Human PPD-based IGRA was positive in 10 (66.7%), negative in 4 (26.7%) and indeterminate in 1 (6.7%) of scar negative patients. Immune responsiveness to human PPD antigens in scar positive and negative children may not correspond with results of the Tuberculin Skin Test. Copyright © 2013 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

  16. Diabetes is associated with lower tuberculosis antigen-specific interferon gamma release in Tanzanian tuberculosis patients and non-tuberculosis controls

    DEFF Research Database (Denmark)

    Faurholt-Jepsen, Daniel; Aabye, Martine Grosos; Jensen, Andreas Vestergaard

    2014-01-01

    in diabetes patients and therefore the validity of interferon gamma release assays (IGRA) may be compromised. The aim of the present study was to assess the association between diabetes and Mycobacterium tuberculosis (Mtb) antigen-specific interferon gamma (IFN-γ) release in a TB endemic area among culture......-confirmed TB patients and non-TB controls. Methods: Culture-confirmed pulmonary TB patients (n = 187) and healthy non-TB neighbourhood controls (n = 190) from Mwanza, Tanzania were tested for the presence of circulating T cells recognizing Mtb antigens using an IGRA. The diabetes status of all participants...

  17. Targeted Recombinant Fusion Proteins of IFN gamma and Mimetic IFN gamma with PDGF beta R Bicyclic Peptide Inhibits Liver Fibrogenesis In Vivo

    NARCIS (Netherlands)

    Bansal, Ruchi; Prakash, Jai; De Ruiter, Marieke; Poelstra, Klaas

    2014-01-01

    Hepatic stellate cells (HSCs), following transdifferentiation to myofibroblasts plays a key role in liver fibrosis. Therefore, attempts to attenuate this myofibroblastic phenotype would be a promising therapeutic approach. Interferon gamma (IFN gamma) is a potent anti-fibrotic cytokine, but its

  18. Continuous in vivo infusion of interferon-gamma (IFN-gamma) enhances engraftment of syngeneic wild-type cells in Fanca-/- and Fancg-/- mice.

    Science.gov (United States)

    Si, Yue; Ciccone, Samantha; Yang, Feng-Chun; Yuan, Jin; Zeng, Daisy; Chen, Shi; van de Vrugt, Henri J; Critser, John; Arwert, Fre; Haneline, Laura S; Clapp, D Wade

    2006-12-15

    Fanconi anemia (FA) is a heterogeneous genetic disorder characterized by bone marrow (BM) failure and cancer susceptibility. Identification of the cDNAs of FA complementation types allows the potential of using gene transfer technology to introduce functional cDNAs as transgenes into autologous stem cells and provide a cure for the BM failure in FA patients. However, strategies to enhance the mobilization, transduction, and engraftment of exogenous stem cells are required to optimize efficacy prior to widespread clinical use. Hypersensitivity of Fancc-/- cells to interferon-gamma (IFN-gamma), a nongenotoxic immune-regulatory cytokine, enhances engraftment of syngeneic wild-type (WT) cells in Fancc-/- mice. However, whether this phenotype is of broad relevance in other FA complementation groups is unresolved. Here we show that primitive and mature myeloid progenitors in Fanca-/- and Fancg-/- mice are hypersensitive to IFN-gamma and that in vivo infusion of IFN-gamma at clinically relevant concentrations was sufficient to allow consistent long-term engraftment of isogenic WT repopulating stem cells. Given that FANCA, FANCC, and FANCG complementation groups account for more than 90% of all FA patients, these data provide evidence that IFN-gamma conditioning may be a useful nongenotoxic strategy for myelopreparation in FA patients.

  19. Effect of beta and gamma neurofeedback on memory and intelligence in the elderly

    NARCIS (Netherlands)

    Staufenbiel, S.M.; Brouwer, A.M.; Keizer, A.W.; Wouwe, N.C. van

    2014-01-01

    Recent research showed a correlation between cognitive decline and a decrease of EEG gamma activity. In the present double-blind randomized control study, we investigated whether gamma and beta neurofeedback protocols, that have been shown to modulate performance on cognitive control and memory in

  20. Negative Role of RIG-I Serine 8 Phosphorylation in the Regulatin of Interferon-beta Production

    Energy Technology Data Exchange (ETDEWEB)

    E Nistal-Villan; M Gack; G Martinez-Delgado; N Maharaj; K Inn; H Yang; R Wang; A Aggarwal; J Jung; A Garcia-Sastre

    2011-12-31

    RIG-I (retinoic acid-inducible gene I) and TRIM25 (tripartite motif protein 25) have emerged as key regulatory factors to induce interferon (IFN)-mediated innate immune responses to limit viral replication. Upon recognition of viral RNA, TRIM25 E3 ligase binds the first caspase recruitment domain (CARD) of RIG-I and subsequently induces lysine 172 ubiquitination of the second CARD of RIG-I, which is essential for the interaction with downstream MAVS/IPS-1/CARDIF/VISA and, thereby, IFN-beta mRNA production. Although ubiquitination has emerged as a major factor involved in RIG-I activation, the potential contribution of other post-translational modifications, such as phosphorylation, to the regulation of RIG-I activity has not been addressed. Here, we report the identification of serine 8 phosphorylation at the first CARD of RIG-I as a negative regulatory mechanism of RIG-I-mediated IFN-beta production. Immunoblot analysis with a phosphospecific antibody showed that RIG-I serine 8 phosphorylation steady-state levels were decreased upon stimulation of cells with IFN-beta or virus infection. Substitution of serine 8 in the CARD RIG-I functional domain with phosphomimetic aspartate or glutamate results in decreased TRIM25 binding, RIG-I ubiquitination, MAVS binding, and downstream signaling. Finally, sequence comparison reveals that only primate species carry serine 8, whereas other animal species carry an asparagine, indicating that serine 8 phosphorylation may represent a primate-specific regulation of RIG-I activation. Collectively, these data suggest that the phosphorylation of RIG-I serine 8 operates as a negative switch of RIG-I activation by suppressing TRIM25 interaction, further underscoring the importance of RIG-I and TRIM25 connection in type I IFN signal transduction.

  1. Dynamic T-lymphocyte chemokine receptor expression induced by interferon-beta therapy in multiple sclerosis

    DEFF Research Database (Denmark)

    Krakauer, M; Sorensen, P S; Khademi, M

    2006-01-01

    chemokine receptor (CXCR)3 was unaltered. Conversely, at 9-12 h after the most recent IFN-beta injection, CCR4, CCR5 and CCR7 expressions were unaltered, while CXCR3 expression was reduced. CD4(+) T-cell surface expression of CCR4 was significantly lower in untreated MS patients compared with healthy...

  2. Lambda Interferon (IFN-gamma), a Type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo

    DEFF Research Database (Denmark)

    Ank, Nina; West, Hans; Bartholdy, C.

    2006-01-01

    Type III interferons (IFNs) (interleukin-28/29 or lambda interferon [IFN-lambda]) are cytokines with IFN-like activities. Here we show that several classes of viruses induce expression of IFN-lambda1 and -lambda2/3 in similar patterns. The IFN-lambdas were-unlike alpha/beta interferon (IFN......-alpha/beta)-induced directly by stimulation with IFN-alpha or -lambda, thus identifying type III IFNs as IFN-stimulated genes. In vitro assays revealed that IFN-lambdas have appreciable antiviral activity against encephalomyocarditis virus (EMCV) but limited activity against herpes simplex virus type 2 (HSV-2), whereas IFN......-alpha potently restricted both viruses. Using three murine models for generalized virus infections, we found that while recombinant IFN-alpha reduced the viral load after infection with EMCV, lymphocytic choriomeningitis virus (LCMV), and HSV-2, treatment with recombinant IFN-lambda in vivo did not affect viral...

  3. Support vector machines for prediction and analysis of beta and gamma-turns in proteins.

    Science.gov (United States)

    Pham, Tho Hoan; Satou, Kenji; Ho, Tu Bao

    2005-04-01

    Tight turns have long been recognized as one of the three important features of proteins, together with alpha-helix and beta-sheet. Tight turns play an important role in globular proteins from both the structural and functional points of view. More than 90% tight turns are beta-turns and most of the rest are gamma-turns. Analysis and prediction of beta-turns and gamma-turns is very useful for design of new molecules such as drugs, pesticides, and antigens. In this paper we investigated two aspects of applying support vector machine (SVM), a promising machine learning method for bioinformatics, to prediction and analysis of beta-turns and gamma-turns. First, we developed two SVM-based methods, called BTSVM and GTSVM, which predict beta-turns and gamma-turns in a protein from its sequence. When compared with other methods, BTSVM has a superior performance and GTSVM is competitive. Second, we used SVMs with a linear kernel to estimate the support of amino acids for the formation of beta-turns and gamma-turns depending on their position in a protein. Our analysis results are more comprehensive and easier to use than the previous results in designing turns in proteins.

  4. Severe respiratory syncytial virus bronchiolitis in infants is associated with reduced airway interferon gamma and substance P.

    Directory of Open Access Journals (Sweden)

    Malcolm G Semple

    2007-10-01

    Full Text Available Severe human respiratory syncytial virus (hRSV bronchiolitis in previously well infants may be due to differences in the innate immune response to hRSV infection.to determine if factors mediating proposed mechanisms for severe bronchiolitis differ with severity of disease.197 infants admitted to hospital with hRSV bronchiolitis were recruited and grouped according to no oxygen requirement (n = 27, oxygen dependence (n = 114 or mechanical ventilation (n = 56. We collected clinical data, nasopharyngeal aspirate (NPA and if ventilated bronchoalveolar lavage (BAL. Interferon-gamma (IFN-gamma, substance P (SP, interleukin 9 (IL-9, urea and hRSV load, were measured in cell free supernatant from NPA and BAL. Multivariate analysis compared independent effects of clinical, virological and immunological variables upon disease severity. IFN-gamma and SP concentrations were lower in NPA from infants who required oxygen or mechanical ventilation. Viral load and IL-9 concentrations were high but did not vary with severity of disease. Independent predictors of severe disease (in diminishing size of effect were low weight on admission, low gestation at birth, low NPA IFN-gamma and NPA SP. Nasal airway sampling appears to be a useful surrogate for distal airway sampling since concentrations of IFN-gamma, SP, IL-9 and viral load in NPA correlate with the same in BAL.Our data support two proposed mechanisms for severe hRSV disease; reduced local IFN-gamma response and SP mediated inflammation. We found large amounts of hRSV and IL-9 in airways secretions from the upper and lower respiratory tract but could not associate these with disease severity.

  5. Clinical trial: a multicentre, randomized, double-blind, placebo-controlled, dose-finding, phase II study of subcutaneous interferon-beta-1a in moderately active ulcerative colitis

    DEFF Research Database (Denmark)

    Pena-Rossi, C; Schreiber, S; Golubovic, G

    2008-01-01

    Background Ulcerative colitis (UC) pathophysiology is characterized by an imbalance between pro- and anti-inflammatory cytokines. Interferon (IFN)-beta-1a has potent immunoregulatory properties, including stimulation of host defence mechanisms, and thus represents a potential treatment. Aim...

  6. Reversible Pulmonary Arterial Hypertension Associated with Interferon-Beta Treatment for Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    E Gibbons

    2015-01-01

    Full Text Available Interferon (IFN therapy has an important role in the treatment of multiple sclerosis and chronic hepatitis C infection. A few case reports have described an association between IFN therapy and the development of irreversible pulmonary arterial hypertension (PAH, and it is currently listed as a possible drug-induced cause of PAH in the most recent classification of pulmonary hypertension. A causal link between IFN use and PAH remains to be elucidated; many reports of PAH resulting from IFN occur in individuals with some other risk factor for PAH. The authors present a case involving a patient with multiple sclerosis with no known risk factors for PAH, who developed severe PAH after exposure to IFN therapy. The patient experienced significant clinical and hemodynamic improvement, with normalization of her pulmonary pressures after the initiation of combination therapy for PAH. At 28 months after diagnosis, she remains asymptomatic with no hemodynamic evidence of PAH and has been off all PAH therapy for 10 months.

  7. A synthetic NCAM-derived mimetic peptide, FGL, exerts anti-inflammatory properties via IGF-1 and interferon-gamma modulation

    DEFF Research Database (Denmark)

    Downer, Eric J; Cowley, Thelma R; Cox, Fionnuala

    2009-01-01

    activation and subsequent pro-inflammatory cytokine production. The aim of the current study was to determine if FGL corrects the age-related imbalance in hippocampal levels of insulin-like growth factor-1 (IGF-1) and pro-inflammatory interferon-gamma (IFNgamma), and subsequently attenuates the glial...

  8. 5HT(4) agonists inhibit interferon-gamma-induced MHC class II and B7 costimulatory molecules expression on cultured astrocytes

    NARCIS (Netherlands)

    Zeinstra, Esther M.; Wilczak, Nadine; Wilschut, Jan C.; Glazenburg, Lisa; Chesik, Daniel; Kroese, Frans G. M.; De Keyser, Jacques

    2006-01-01

    A failure of tight control of MHC class II expression on astrocytes may play a role in the development of autoimmune responses in multiple sclerosis. The 5-HT4 serotonin receptor agonists cisapride and prucalopride, at concentrations between 10(-10) M and 10(-8) M, reduced interferon-gamma-induced

  9. Cell Death of Gamma Interferon-Stimulated Human Fibroblasts upon Toxoplasma gondii Infection Induces Early Parasite Egress and Limits Parasite Replication

    NARCIS (Netherlands)

    Niedelman, Wendy; Sprokholt, Joris K.; Clough, Barbara; Frickel, Eva-Maria; Saeij, Jeroen P. J.

    2013-01-01

    The intracellular protozoan parasite Toxoplasma gondii is a major food-borne illness and opportunistic infection for the immunosuppressed. Resistance to Toxoplasma is dependent on gamma interferon (IFN-γ) activation of both hematopoietic and nonhematopoietic cells. Although IFN-γ-induced innate

  10. Cell death of gamma interferon-stimulated human fibroblasts upon toxoplasma gondii infection induces early parasite egress and limits parasite replication

    NARCIS (Netherlands)

    Niedelman, W.; Sprokholt, J.K.; Clough, B.; Frickel, E.; Saeij, J.P.J.

    2013-01-01

    The intracellular protozoan parasite Toxoplasma gondii is a major food-borne illness and opportunistic infection for the immunosuppressed. Resistance to Toxoplasma is dependent on gamma interferon (IFN-¿) activation of both hematopoietic and nonhematopoietic cells. Although IFN-¿-induced innate

  11. Treatment of visceral leishmaniasis in a patient with AIDS with antimony and gamma-interferon: remission and prevention of relapse by maintenance therapy with weekly pentamidine

    NARCIS (Netherlands)

    Lustig, V.; Kager, P. A.; Meenhorst, P. L.

    1995-01-01

    A 41-year-old AIDS patient with fever, nightly perspiration, diarrhoea, anaemia and leukopenia was diagnosed as having visceral leishmaniasis (VL). After 8 weeks of antimony treatment combined with gamma-interferon, given in 2 courses of 3 and 5 weeks, 12 weeks apart, the bone marrow revealed no

  12. Myxoma virus M-T7, a secreted homolog of the interferon-gamma receptor, is a critical virulence factor for the development of myxomatosis in European rabbits.

    Science.gov (United States)

    Mossman, K; Nation, P; Macen, J; Garbutt, M; Lucas, A; McFadden, G

    1996-01-01

    Myxoma virus is a leporipoxvirus of New World rabbits (Sylvilagus sp.) that induces a rapidly lethal infection known as myxomatosis in the European rabbit (Oryctolagus cuniculus). Like all poxviruses, myxoma virus encodes a plethora of proteins to circumvent or inhibit a variety of host antiviral immune mechanisms. M-T7, the most abundantly secreted protein of myxoma virus-infected cells, was originally identified as an interferon-gamma receptor homolog (Upton, Mossman, and McFadden, Science 258, 1369-1372, 1992). Here, we demonstrate that M-T7 is dispensable for virus replication in cultured cells but is a critical virulence factor for virus pathogenesis in European rabbits. Disruption of both copies of the M-T7 gene in myxoma virus was achieved by the deletion of 372 bp of M-T7 coding sequences, replacement with a selectable marker, p7.5Ecogpt, and selection of a recombinant virus (vMyxlac-T7gpt) resistant to mycophenolic acid. vMyxlac-T7gpt expressed no detectable M-T7 protein and infected cells supernatants were devoid of any detectable interferon-gamma binding activities. Immunohistochemical staining with anti-beta-galactosidase and anti-CD43 antibodies demonstrated that in vMyxlac-T7gpt-infected rabbits the loss of M-T7 not only caused a dramatic reduction in disease symptoms and viral dissemination to secondary sites, but also dramatically influenced host leukocyte behavior. Notably, primary lesions in wild-type virus infections were generally underlayed by large masses of inflammatory cells that did not effectively migrate into the dermal sites of viral replication, whereas in vMyxlac-T7gpt infections this apparent block to leukocyte influx was relieved. A second major phenotypic distinction noted for the M-T7 knockout virus was the extensive activation of lymphocytes in secondary immune organs, particularly the spleen and lymph nodes, by Day 4 of the infection. This is in stark contrast to infection by wild-type myxoma virus, which results in relatively

  13. Gamma and beta logging of underground sewer and process lines

    International Nuclear Information System (INIS)

    Rangel, M.J.; Martz, D.E.; Langner, G.H. Jr.

    1989-11-01

    The GammaSnake can be useful for locating uranium mill tailings used as backfill for sewer lines or storm drains where the lines can be readily accessed from a cleanout access port or other opening. The time required to determine if contamination is present using the GammaSnake method is considerably less than when using the delta gamma or drilling methods. There is, also, less potential hazard to the equipment operators when using the GammaSnake method. The GammaSnake method is generally limited to a distance of 100 feet or less. Used with the MAC-51B line locator, the GammaSnake method can provide useful information without extensive drilling or surveying. 7 figs., 2 tabs

  14. Is serum neopterin level a marker of responsiveness to interferon beta-1a therapy in multiple sclerosis?

    Science.gov (United States)

    Casoni, F; Merelli, E; Bedin, R; Sola, P; Bertolotto, A; Faglioni, P

    2004-01-01

    Interferon beta (INFbeta) may induce the expression of several proteins, including neopterin, considered a biological marker of INFbeta activity. The aim of this study was to determine the serum neopterin concentration at the beginning of, and during, IFNbeta-1a therapy in relapsing-remitting multiple sclerosis (r-r MS) patients, and to look for a possible correlation between protein synthesis and the clinical course of the disease. Thirteen r-r MS patients were treated with INFbeta-1a (i.m. 6 MIU/week) for 2 years. Blood samples for neopterin determinations were taken daily over a period of 1 week at the end of each 6 months of therapy, and tested for neutralizing antibodies (NABs). Neopterin levels peaked 24-48 h post-injection and returned to baseline after 120 h. After 1 year of therapy, four patients dropped out of the study because of progression of the disease: in these subjects a significant decrement of neopterin was observed. Neopterin baseline values were not found to decrease over the 2 years of therapy, and neopterin may be considered to be a useful marker of responsiveness to IFNbeta.

  15. Characteristics of alpha/beta interferon induction after infection of murine fibroblasts with wild-type and mutant alphaviruses

    International Nuclear Information System (INIS)

    Burke, Crystal W.; Gardner, Christina L.; Steffan, Joshua J.; Ryman, Kate D.; Klimstra, William B.

    2009-01-01

    We examined the characteristics of interferon alpha/beta (IFN-α/β) induction after alphavirus or control Sendai virus (SeV) infection of murine fibroblasts (MEFs). As expected, SeV infection of wild-type (wt) MEFs resulted in strong dimerization of IRF3 and the production of high levels of IFN-α/β. In contrast, infection of MEFs with multiple alphaviruses failed to elicit detectable IFN-α/β. In more detailed studies, Sindbis virus (SINV) infection caused dimerization and nuclear migration of IRF3, but minimal IFN-β promoter activity, although surprisingly, the infected cells were competent for IFN production by other stimuli early after infection. A SINV mutant defective in host macromolecular synthesis shutoff induced IFN-α/β in the MEF cultures dependent upon the activities of the TBK1 IRF3 activating kinase and host pattern recognition receptors (PRRs) PKR and MDA5 but not RIG-I. These results suggest that wild-type alphaviruses antagonize IFN induction after IRF3 activation but also may avoid detection by host PRRs early after infection.

  16. Study of radiation detectors response in standard X, gamma and beta radiation standard beams

    International Nuclear Information System (INIS)

    Nonato, Fernanda Beatrice Conceicao

    2010-01-01

    The response of 76 Geiger-Mueller detectors, 4 semiconductor detectors and 34 ionization chambers were studied. Many of them were calibrated with gamma radiation beams ( 37 Cs and 60 Co), and some of them were tested in beta radiation ( 90 Sr+ 9' 0Y e 204 Tl) and X radiation (N-60, N-80, N-100, N-150) beams. For all three types of radiation, the calibration factors of the instruments were obtained, and the energy and angular dependences were studied. For beta and gamma radiation, the angular dependence was studied for incident radiation angles of 0 deg and +- 45 deg. The curves of the response of the instruments were obtained over an angle interval of 0 deg to +- 90 deg, for gamma, beta and X radiations. The calibration factors obtained for beta radiation were compared to those obtained for gamma radiation. For gamma radiation, 24 of the 66 tested Geiger-Mueller detectors presented results for the energy dependence according to international recommendation of ISO 4037-2 and 56 were in accordance with the Brazilian ABNT 10011 recommendation. The ionization chambers and semiconductors were in accordance to national and international recommendations. All instruments showed angular dependence less than 40%. For beta radiation, the instruments showed unsatisfactory results for the energy dependence and angular dependence. For X radiation, the ionization chambers presented results for energy dependence according to the national recommendation, and the angular dependence was less than 40%. (author)

  17. Differential expression of largemouth bass (Micropterus salmoides) estrogen receptor isotypes alpha, beta, and gamma by estradiol.

    Science.gov (United States)

    Sabo-Attwood, Tara; Kroll, Kevin J; Denslow, Nancy D

    2004-04-15

    The expression levels of three estrogen receptor (ER) isotypes alpha, beta, and gamma were quantified in female largemouth bass (Micropterus salmoides) (LMB) liver, ovary, brain, and pituitary tissues. ER alpha and beta expression predominated in the liver, while ERs beta and gamma predominated in the other tissues. Temporally in females, ER alpha was highly up-regulated, ER gamma was slightly up-regulated, and ER beta levels remained unchanged in the liver when plasma 17-beta estradiol (E2) and vitellogenin (Vtg) levels were elevated in the spring. In ovarian tissue from these same fish, all three ERs were maximally expressed in the fall, during early oocyte development and prior to peak plasma E2 levels. When males were injected with E2, ER alpha was highly inducible, ER gamma was moderately up-regulated, and ER beta levels were not affected. None of the ER isotypes were induced by E2 in gonadal tissues. These results combined suggest that the ERs themselves are not regulated in the same manner by E2, and furthermore, do not contribute equally to the transcriptional regulation of genes involved in fish reproduction such as Vtg.

  18. Growth hormone, interferon-gamma, and leukemia inhibitory factor promoted tyrosyl phosphorylation of insulin receptor substrate-1

    DEFF Research Database (Denmark)

    Argetsinger, L S; Hsu, G W; Myers, M G

    1995-01-01

    ), the principle substrate of the insulin receptor. Tyrosyl phosphorylation of IRS-1 is a critical step in insulin signaling and provides binding sites for proteins with the appropriate Src homology 2 domains, including the 85-kDa regulatory subunit of phosphatidylinositol (PI) 3'-kinase. In 3T3-F442A fibroblasts......., Campbell, G. S., Allevato, G., Billestrup, N., Norstedt, G., and Carter-Su, C. (1994) J. Biol. Chem. 269, 21709-21717). When other cytokines that activate JAK2 were tested for the ability to stimulate the tyrosyl phosphorylation of IRS-1, stimulation was detected with interferon-gamma and leukemia...... to JAK2. GH is also shown to stimulate binding of IRS-1 to the 85-kDa regulatory subunit of PI 3'-kinase. The ability of GH to stimulate tyrosyl phosphorylation of IRS-1 and its association with PI 3'-kinase provides a biochemical basis for responses shared by insulin and GH including the well...

  19. Use of Novel Recombinant Antigens in the Interferon Gamma Assay for Detection of Mycobacterium Avium Subsp. Paratuberculosis Infection in Cattle

    DEFF Research Database (Denmark)

    Mikkelsen, Heidi; Aagaard, Claus; Nielsen, Søren Saxmose

    2012-01-01

    of the study were to evaluate immunogenicity and specificity of 14 novel recombinant antigens for use in the IFN-γ assay and to assess the consistency of IFN-γ responses. The antigens used were 4 ESAT-6 family members, 4 latency proteins, 4 secreted proteins including Ag85B, 3 other antigens and PPDj......Early stage Mycobacterium avium subsp. paratuberculosis (MAP) infection can be detected by measuring antigen specific cell mediated immune responses by the interferon gamma (IFN-γ) assay. Available IFN-γ assay use purified protein derivate of Johnin (PPDj) leading to low specificity. The objectives...... of the infected and non-infected herds were significantly (Passay using PPDj did not correlate with the results using the novel antigens since 5 of the 17 animals that were positive to PPDj were...

  20. Potentiating day-old blood samples for detection of interferon-gamma responses following infection with Mycobacterium avium subsp. paratuberculosis

    DEFF Research Database (Denmark)

    Mikkelsen, Heidi; Nielsen, Søren Saxmose; Jungersen, Gregers

    time interval from blood sampling to culture. The objective of the study was to assess options for use of day-old blood samples for early-stage diagnosis of MAP infections. Bovine interleukin 12 (IL-12) can induce, and IL-10 reduce, IFN-γ production. Therefore, addition of IL-12 and anti-IL-10 could...... result in production of IFN-γ in samples previously exposed to MAP antigens. Whole blood samples were collected from heifers in a Danish dairy herd known to be infected with MAP. The samples were collected on three sample dates, and on each date the blood samples were stimulated with PPDj and recombinant......The interferon gamma (IFN-γ) test measuring specific cell-mediated immune responses in whole blood can be used for diagnosis at an early stage of Mycobacterium avium subsp. paratuberculosis (MAP) infection. A major obstacle for the practical use of IFN-γ testing is the recommended maximum 8 hour...

  1. CMOS image sensor for detection of interferon gamma protein interaction as a point-of-care approach.

    Science.gov (United States)

    Marimuthu, Mohana; Kandasamy, Karthikeyan; Ahn, Chang Geun; Sung, Gun Yong; Kim, Min-Gon; Kim, Sanghyo

    2011-09-01

    Complementary metal oxide semiconductor (CMOS)-based image sensors have received increased attention owing to the possibility of incorporating them into portable diagnostic devices. The present research examined the efficiency and sensitivity of a CMOS image sensor for the detection of antigen-antibody interactions involving interferon gamma protein without the aid of expensive instruments. The highest detection sensitivity of about 1 fg/ml primary antibody was achieved simply by a transmission mechanism. When photons are prevented from hitting the sensor surface, a reduction in digital output occurs in which the number of photons hitting the sensor surface is approximately proportional to the digital number. Nanoscale variation in substrate thickness after protein binding can be detected with high sensitivity by the CMOS image sensor. Therefore, this technique can be easily applied to smartphones or any clinical diagnostic devices for the detection of several biological entities, with high impact on the development of point-of-care applications.

  2. Mixing of ground-state rotational and gamma and beta vibrational bands in the region A>=228

    Energy Technology Data Exchange (ETDEWEB)

    Mittal, R; Sahota, H S [Punjabi Univ., Patiala (India). Dept. of Physics

    1983-06-21

    The mixing of beta, gamma and ground-state bands has been investigated through the experimental determination of mixing parameters Zsub(..gamma..) and Zsub(..beta gamma..). These Zsub(..gamma..) values have been compared with the theoretical calculations of this parameter from the solutions of time-dependent HFB equations on the adiabatic and nonadiabatic assumptions. The experimental values are in better agreement with the results obtained under the nonadiabatic assumption, valid for small deviations from the spherical symmetry.

  3. Pilot study of human recombinant interferon gamma and accelerated hyperfractionated thoracic radiation therapy in patients with unresectable stage IIIA/B nonsmall cell lung cancer

    International Nuclear Information System (INIS)

    Shaw, Edward G.; Deming, Richard L.; Creagan, Edward T.; Nair, Suresh; Su, John Q.; Levitt, Ralph; Steen, Preston D.; Wiesenfeld, Martin; Mailliard, James A.

    1995-01-01

    Purpose: Gamma interferon has a wide range of properties, including the ability to sensitize solid tumor cells to the effects of ionizing radiation. The North Central Cancer Treatment Group has previously completed pilot studies of accelerated hyperfractionated thoracic radiation therapy (AHTRT) in patients with unresectable Stage IIIA/B nonsmall cell lung cancer (NSCLC). This Phase I study was designed to assess the toxicity of concomitant gamma interferon and AHTRT in a similar patient population. Methods and Materials: Between December 1991 and May 1992, 18 patients with unresectable Stage IIIA/B NSCLC were treated with daily gamma interferon (0.2 mg subcutaneously) concomitant with AHTRT (60 Gy given in 1.5 Gy twice daily fractions). All patients had an Eastern Cooperative Oncology Group performance status of 0 or 1 with weight loss < 5%. Eight patients had Stage IIIA and 10 had Stage IIIB disease. Results: Nine patients (50%) experienced severe, life-threatening, or fatal toxicities. Eight of the patients (44%) developed significant radiation pneumonitis, which was severe in six patients and fatal in two patients (11% treatment-related mortality). Two patients (11%) developed severe radiation esophagitis. With follow-up of 15-21 months, 2 patients are alive, and 16 have died. The median survival time and 1-year survival rate is 7.8 months and 38%, respectively. Conclusion: Gamma interferon appeared to sensitize normal lung tissue to the effects of radiation, as demonstrated by the high incidence of severe or fatal radiation pneumonitis. We do not recommend pursuing gamma interferon as a radiosensitizer in this setting

  4. A randomized, double-blind, phase I/II trial of tumor necrosis factor and interferon-gamma for treatment of AIDS-related complex (Protocol 025 from the AIDS Clinical Trials Group).

    Science.gov (United States)

    Agosti, J M; Coombs, R W; Collier, A C; Paradise, M A; Benedetti, J K; Jaffe, H S; Corey, L

    1992-05-01

    To determine safety and efficacy of tumor necrosis factor (TNF) and interferon-gamma (IFN gamma) in the treatment of patients with acquired immunodeficiency syndrome (AIDS)-related complex, a randomized, double-blind study was conducted. Twenty-five patients with AIDS-related complex and CD4 lymphocytes less than or equal to 500 x 10(6)/L attended an AIDS Clinical Trials Unit of a tertiary referral center. Patients were administered tumor necrosis factor (TNF) (10 micrograms/m2) or IFN gamma (10 micrograms/m2), or both intramuscularly three times weekly for 16 weeks. Side effects from all three preparations included fever, constitutional symptoms, and local reactions. No significant hematologic, hepatic, renal, or coagulation abnormalities were observed. CD4 lymphocyte counts, beta 2-microglobulin, p24 antigen levels, and anti-p24 antibody did not change significantly during therapy. Similarly, no significant change was noted in rates of HIV isolation from peripheral blood mononuclear cells or plasma. TNF and IFN gamma were tolerable after premedication with acetaminophen; however, no significant change in markers of human immunodeficiency virus infection was demonstrated. These cytokines alone do not appear to be of benefit, nor do they appear to hasten the progression of HIV infection.

  5. Functions of Beta- and Gamma-Catenins in Prostate Cancer

    National Research Council Canada - National Science Library

    Reed, John

    2001-01-01

    .... We recently discovered that the protein Siah-1 interacts with the APC/catenin complex, and regulates the ubiquitin-dependent turnover of beta-catenin through a novel previously unidentified mechanism...

  6. Optimization of plastic scintillator thicknesses for online beta/gamma detection

    Directory of Open Access Journals (Sweden)

    Pourtangestani K.

    2012-04-01

    Full Text Available For efficient beta detection in a mixed beta gamma field, Monte Carlo simulation models have been built to optimize the thickness of a plastic scintillator, used in a whole body monitor. The simulation has been performed using the MCNP/X code for different thicknesses of plastic scintillator from 150 μm to 600 μm. The relationship between the thickness of the scintillator and the efficiency of the detector has been analyzed. For 150 μm thickness, an experimental investigation has been conducted with different beta sources at different positions on the scintillator and the counting efficiency of the unit has been measured. Evaluated data along with experimental ones have been discussed. A thickness of 300 μm to 500 μm has been found to be the optimum thickness for high efficiency beta detection in the presence of low energy gamma-rays.

  7. Ornithogalum virens as a plant assay for beta and gamma radiation effects

    International Nuclear Information System (INIS)

    Herron, V.J.

    1979-01-01

    The purpose of this study was to determine if the monocotyledonous angiosperm, Ornithogalum virens (Quintanilha and Cabral, 1947), could be used in such a biological assay system. After exposing O. virens plants to acute ( 60 Co) and chronic ( 137 Cs) gamma radiation and internal beta radiation ( 32 P), lethality (LD 50 , LD 100 ), growth inhibition, and chromosome aberrations were investigated. The LD 50 and LD 100 for acute gamma radiation were estimated to be between 0.91 to 1.8 krad and less than 3.6 krad, respectively. Though growth inhibition and abnormal growth were observed in the acute and chronic gamma radiation studies, the changes in the growth of the plants were so variable that these parameters were found to be unreliable measures of radiation effects. Chromosome aberrations were a more reliable measure of radiation damage because linear relationships between total aberrations and dose were found for both gamma and beta radiation

  8. Determination of $\\gamma$ and $-2\\beta_s$ from charmless two-body decays of beauty mesons

    CERN Document Server

    Aaij, Roel; Adeva, Bernardo; Adinolfi, Marco; Affolder, Anthony; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Anderson, Jonathan; Andreassen, Rolf; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Belogurov, Sergey; Belous, Konstantin; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bien, Alexander; Bifani, Simone; Bird, Thomas; Bizzeti, Andrea; Bjørnstad, Pål Marius; Blake, Thomas; Blanc, Frédéric; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borghi, Silvia; Borgia, Alessandra; Borsato, Martino; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Brambach, Tobias; Bressieux, Joël; Brett, David; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Brook, Nicholas; Brown, Henry; Bursche, Albert; Busetto, Giovanni; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Campana, Pierluigi; Campora Perez, Daniel; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu-Faye; Chiapolini, Nicola; Chrzaszcz, Marcin; Ciba, Krzystof; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Cojocariu, Lucian; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coombes, Matthew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Counts, Ian; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dalseno, Jeremy; David, Pascal; David, Pieter; Davis, Adam; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Silva, Weeraddana; De Simone, Patrizia; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Déléage, Nicolas; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Di Canto, Angelo; Dijkstra, Hans; Donleavy, Stephanie; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dossett, David; Dovbnya, Anatoliy; Dreimanis, Karlis; Dujany, Giulio; Dupertuis, Frederic; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; El Rifai, Ibrahim; Elsasser, Christian; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Färber, Christian; Farinelli, Chiara; Farley, Nathanael; Farry, Stephen; Fay, Robert; Ferguson, Dianne; Fernandez Albor, Victor; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fol, Philip; Fontana, Marianna; Fontanelli, Flavio; Forty, Roger; Francisco, Oscar; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Fu, Jinlin; Furfaro, Emiliano; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; García Pardiñas, Julián; Garofoli, Justin; Garra Tico, Jordi; Garrido, Lluis; Gaspar, Clara; Gauld, Rhorry; Gavardi, Laura; Gavrilov, Gennadii; Geraci, Angelo; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianelle, Alessio; Gianì, Sebastiana; Gibson, Valerie; Giubega, Lavinia-Helena; Gligorov, Vladimir; Göbel, Carla; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graziani, Giacomo; Grecu, Alexandru; Greening, Edward; Gregson, Sam; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gui, Bin; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Hampson, Thomas; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; He, Jibo; Head, Timothy; Heijne, Veerle; Hennessy, Karol; Henrard, Pierre; Henry, Louis; Hernando Morata, Jose Angel; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hoballah, Mostafa; Hombach, Christoph; Hulsbergen, Wouter; Hunt, Philip; Hussain, Nazim; Hutchcroft, David; Hynds, Daniel; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jaton, Pierre; Jawahery, Abolhassan; Jing, Fanfan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kaballo, Michael; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Karbach, Moritz; Karodia, Sarah; Kelsey, Matthew; Kenyon, Ian; Ketel, Tjeerd; Khanji, Basem; Khurewathanakul, Chitsanu; Klaver, Suzanne; Klimaszewski, Konrad; Kochebina, Olga; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Korolev, Mikhail; Kozlinskiy, Alexandr; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krocker, Georg; Krokovny, Pavel; Kruse, Florian; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kurek, Krzysztof; Kvaratskheliya, Tengiz; La Thi, Viet Nga; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lambert, Robert W; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Lefèvre, Regis; Leflat, Alexander; Lefrançois, Jacques; Leo, Sabato; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Yiming; Likhomanenko, Tatiana; Liles, Myfanwy; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Lohn, Stefan; Longstaff, Iain; Lopes, Jose; Lopez-March, Neus; Lowdon, Peter; Lu, Haiting; Lucchesi, Donatella; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Machefert, Frederic; Machikhiliyan, Irina V; Maciuc, Florin; Maev, Oleg; Malde, Sneha; Malinin, Alexander; Manca, Giulia; Mancinelli, Giampiero; Mapelli, Alessandro; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Märki, Raphael; Marks, Jörg; Martellotti, Giuseppe; Martens, Aurelien; Martín Sánchez, Alexandra; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massafferri, André; Matev, Rosen; Mathe, Zoltan; Matteuzzi, Clara; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; McSkelly, Ben; Meadows, Brian; Meier, Frank; Meissner, Marco; Merk, Marcel; Milanes, Diego Alejandro; Minard, Marie-Noelle; Moggi, Niccolò; Molina Rodriguez, Josue; Monteil, Stephane; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Müller, Katharina; Mussini, Manuel; Muster, Bastien; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen, Thi-Dung; Nguyen-Mau, Chung; Nicol, Michelle; Niess, Valentin; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Novoselov, Alexey; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Oggero, Serena; Ogilvy, Stephen; Okhrimenko, Oleksandr; Oldeman, Rudolf; Onderwater, Gerco; Orlandea, Marius; Otalora Goicochea, Juan Martin; Owen, Patrick; Oyanguren, Maria Arantza; Pal, Bilas Kanti; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Parkes, Christopher; Parkinson, Christopher John; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pazos Alvarez, Antonio; Pearce, Alex; Pellegrino, Antonio; Pepe Altarelli, Monica; Perazzini, Stefano; Perez Trigo, Eliseo; Perret, Pascal; Perrin-Terrin, Mathieu; Pescatore, Luca; Pesen, Erhan; Petridis, Konstantin; Petrolini, Alessandro; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pilař, Tomas; Pinci, Davide; Pistone, Alessandro; Playfer, Stephen; Plo Casasus, Maximo; Polci, Francesco; Poluektov, Anton; Polycarpo, Erica; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Price, Eugenia; Price, Joseph David; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Rachwal, Bartolomiej; Rademacker, Jonas; Rakotomiaramanana, Barinjaka; Rama, Matteo; Rangel, Murilo; Raniuk, Iurii; Rauschmayr, Nathalie; Raven, Gerhard; Redi, Federico; Reichert, Stefanie; Reid, Matthew; dos Reis, Alberto; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vincente; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Perez, Pablo; Roiser, Stefan; Romanovsky, Vladimir; Romero Vidal, Antonio; Rotondo, Marcello; Rouvinet, Julien; Ruf, Thomas; Ruiz, Hugo; Ruiz Valls, Pablo; Saborido Silva, Juan Jose; Sagidova, Naylya; Sail, Paul; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santovetti, Emanuele; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrie, Mauro; Savrina, Darya; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Seco, Marcos; Semennikov, Alexander; Sepp, Indrek; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Silva Coutinho, Rafael; Simi, Gabriele; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Anthony; Smith, Edmund; Smith, Eluned; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Soomro, Fatima; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Sparkes, Ailsa; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Steinkamp, Olaf; Stenyakin, Oleg; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Stroili, Roberto; Subbiah, Vijay Kartik; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szczypka, Paul; Szilard, Daniela; Szumlak, Tomasz; T'Jampens, Stephane; Teklishyn, Maksym; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Tolk, Siim; Tomassetti, Luca; Topp-Joergensen, Stig; Torr, Nicholas; Tournefier, Edwige; Tourneur, Stephane; Tran, Minh Tâm; Tresch, Marco; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ubeda Garcia, Mario; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vacca, Claudia; Vagnoni, Vincenzo; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vázquez Sierra, Carlos; Vecchi, Stefania; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Vollhardt, Achim; Volyanskyy, Dmytro; Voong, David; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; Voss, Helge; de Vries, Jacco; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wandernoth, Sebastian; Wang, Jianchun; Ward, David; Watson, Nigel; Websdale, David; Whitehead, Mark; Wicht, Jean; Wiedner, Dirk; Wilkinson, Guy; Williams, Matthew; Williams, Mike; Wilschut, Hans; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wright, Simon; Wyllie, Kenneth; Xie, Yuehong; Xing, Zhou; Xu, Zhirui; Yang, Zhenwei; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Wen Chao; Zhang, Yanxi; Zhelezov, Alexey; Zhokhov, Anatoly; Zhong, Liang; Zvyagin, Alexander

    2015-01-01

    Using the latest LHCb measurements of time-dependent $C\\!P$ violation in the $B^0_s \\to K^+K^-$ decay, a U-spin relation between the decay amplitudes of $B^0_s \\to K^+K^-$ and $B^0\\to \\pi^+\\pi^-$ decay processes allows constraints to be placed on the angle $\\gamma$ of the unitarity triangle and on the $B^0_s$ mixing phase $-2\\beta_s$. Results from an extended approach, which uses additional inputs on $B^0\\to \\pi^0\\pi^0$ and $B^+\\to \\pi^+\\pi^0$ decays from other experiments and exploits isospin symmetry, are also presented. The dependence of the results on the maximum allowed amount of U-spin breaking is studied. At 68% probability, the value $\\gamma = \\left( 63.5^{\\,+\\, 7.2}_{\\,-\\,6.7} \\right)^\\circ~\\mathrm{modulo}~180^\\circ$ is determined. In an alternative analysis, the value $-2\\beta_s = -0.12 ^{\\,+\\,0.14}_{\\,-\\,0.16}\\,\\,\\mathrm{rad}$ is found. In both measurements, the uncertainties due to U-spin breaking effects up to 50% are included.

  9. Determination of $\\gamma$ and $-2\\beta_s$ from charmless two-body decays of beauty mesons

    CERN Document Server

    Aaij, Roel; Adeva, Bernardo; Adinolfi, Marco; Affolder, Anthony; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Anderson, Jonathan; Andreassen, Rolf; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Belogurov, Sergey; Belous, Konstantin; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bien, Alexander; Bifani, Simone; Bird, Thomas; Bizzeti, Andrea; Bjørnstad, Pål Marius; Blake, Thomas; Blanc, Frédéric; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borghi, Silvia; Borgia, Alessandra; Borsato, Martino; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Brambach, Tobias; Bressieux, Joël; Brett, David; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Brook, Nicholas; Brown, Henry; Bursche, Albert; Busetto, Giovanni; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Campana, Pierluigi; Campora Perez, Daniel; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu-Faye; Chiapolini, Nicola; Chrzaszcz, Marcin; Ciba, Krzystof; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Cojocariu, Lucian; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coombes, Matthew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Counts, Ian; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dalseno, Jeremy; David, Pascal; David, Pieter; Davis, Adam; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Silva, Weeraddana; De Simone, Patrizia; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Déléage, Nicolas; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Di Canto, Angelo; Dijkstra, Hans; Donleavy, Stephanie; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dossett, David; Dovbnya, Anatoliy; Dreimanis, Karlis; Dujany, Giulio; Dupertuis, Frederic; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; El Rifai, Ibrahim; Elsasser, Christian; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Färber, Christian; Farinelli, Chiara; Farley, Nathanael; Farry, Stephen; Fay, Robert; Ferguson, Dianne; Fernandez Albor, Victor; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fol, Philip; Fontana, Marianna; Fontanelli, Flavio; Forty, Roger; Francisco, Oscar; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Fu, Jinlin; Furfaro, Emiliano; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; García Pardiñas, Julián; Garofoli, Justin; Garra Tico, Jordi; Garrido, Lluis; Gaspar, Clara; Gauld, Rhorry; Gavardi, Laura; Gavrilov, Gennadii; Geraci, Angelo; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianelle, Alessio; Gianì, Sebastiana; Gibson, Valerie; Giubega, Lavinia-Helena; Gligorov, V.V.; Göbel, Carla; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graziani, Giacomo; Grecu, Alexandru; Greening, Edward; Gregson, Sam; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gui, Bin; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Hampson, Thomas; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; He, Jibo; Head, Timothy; Heijne, Veerle; Hennessy, Karol; Henrard, Pierre; Henry, Louis; Hernando Morata, Jose Angel; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hoballah, Mostafa; Hombach, Christoph; Hulsbergen, Wouter; Hunt, Philip; Hussain, Nazim; Hutchcroft, David; Hynds, Daniel; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jaton, Pierre; Jawahery, Abolhassan; Jing, Fanfan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kaballo, Michael; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Karbach, Moritz; Karodia, Sarah; Kelsey, Matthew; Kenyon, Ian; Ketel, Tjeerd; Khanji, Basem; Khurewathanakul, Chitsanu; Klaver, Suzanne; Klimaszewski, Konrad; Kochebina, Olga; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Korolev, Mikhail; Kozlinskiy, Alexandr; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krocker, Georg; Krokovny, Pavel; Kruse, Florian; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kurek, Krzysztof; Kvaratskheliya, Tengiz; La Thi, Viet Nga; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lambert, Robert W; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Lefèvre, Regis; Leflat, Alexander; Lefrançois, Jacques; Leo, Sabato; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Yiming; Likhomanenko, Tatiana; Liles, Myfanwy; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Lohn, Stefan; Longstaff, Iain; Lopes, Jose; Lopez-March, Neus; Lowdon, Peter; Lu, Haiting; Lucchesi, Donatella; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Machefert, Frederic; Machikhiliyan, Irina V; Maciuc, Florin; Maev, Oleg; Malde, Sneha; Malinin, Alexander; Manca, Giulia; Mancinelli, Giampiero; Mapelli, Alessandro; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Märki, Raphael; Marks, Jörg; Martellotti, Giuseppe; Martens, Aurelien; Martín Sánchez, Alexandra; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massafferri, André; Matev, Rosen; Mathe, Zoltan; Matteuzzi, Clara; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; McSkelly, Ben; Meadows, Brian; Meier, Frank; Meissner, Marco; Merk, Marcel; Milanes, Diego Alejandro; Minard, Marie-Noelle; Moggi, Niccolò; Molina Rodriguez, Josue; Monteil, Stephane; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Müller, Katharina; Mussini, Manuel; Muster, Bastien; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen, Thi-Dung; Nguyen-Mau, Chung; Nicol, Michelle; Niess, Valentin; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Novoselov, Alexey; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Oggero, Serena; Ogilvy, Stephen; Okhrimenko, Oleksandr; Oldeman, Rudolf; Onderwater, Gerco; Orlandea, Marius; Otalora Goicochea, Juan Martin; Owen, Patrick; Oyanguren, Maria Arantza; Pal, Bilas Kanti; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Parkes, Christopher; Parkinson, Christopher John; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pazos Alvarez, Antonio; Pearce, Alex; Pellegrino, Antonio; Pepe Altarelli, Monica; Perazzini, Stefano; Perez Trigo, Eliseo; Perret, Pascal; Perrin-Terrin, Mathieu; Pescatore, Luca; Pesen, Erhan; Petridis, Konstantin; Petrolini, Alessandro; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pilař, Tomas; Pinci, Davide; Pistone, Alessandro; Playfer, Stephen; Plo Casasus, Maximo; Polci, Francesco; Poluektov, Anton; Polycarpo, Erica; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Price, Eugenia; Price, Joseph David; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Rachwal, Bartolomiej; Rademacker, Jonas; Rakotomiaramanana, Barinjaka; Rama, Matteo; Rangel, Murilo; Raniuk, Iurii; Rauschmayr, Nathalie; Raven, Gerhard; Redi, Federico; Reichert, Stefanie; Reid, Matthew; dos Reis, Alberto; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vincente; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Perez, Pablo; Roiser, Stefan; Romanovsky, Vladimir; Romero Vidal, Antonio; Rotondo, Marcello; Rouvinet, Julien; Ruf, Thomas; Ruiz, Hugo; Ruiz Valls, Pablo; Saborido Silva, Juan Jose; Sagidova, Naylya; Sail, Paul; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santovetti, Emanuele; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrie, Mauro; Savrina, Darya; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Seco, Marcos; Semennikov, Alexander; Sepp, Indrek; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Silva Coutinho, Rafael; Simi, Gabriele; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Anthony; Smith, Edmund; Smith, Eluned; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Soomro, Fatima; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Sparkes, Ailsa; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Steinkamp, Olaf; Stenyakin, Oleg; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Stroili, Roberto; Subbiah, Vijay Kartik; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szczypka, Paul; Szilard, Daniela; Szumlak, Tomasz; T'Jampens, Stephane; Teklishyn, Maksym; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Tolk, Siim; Tomassetti, Luca; Topp-Joergensen, Stig; Torr, Nicholas; Tournefier, Edwige; Tourneur, Stephane; Tran, Minh Tâm; Tresch, Marco; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ubeda Garcia, Mario; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vacca, Claudia; Vagnoni, Vincenzo; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vázquez Sierra, Carlos; Vecchi, Stefania; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Vollhardt, Achim; Volyanskyy, Dmytro; Voong, David; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; Voss, Helge; de Vries, Jacco; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wandernoth, Sebastian; Wang, Jianchun; Ward, David; Watson, Nigel; Websdale, David; Whitehead, Mark; Wicht, Jean; Wiedner, Dirk; Wilkinson, Guy; Williams, Matthew; Williams, Mike; Wilschut, Hans; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wright, Simon; Wyllie, Kenneth; Xie, Yuehong; Xing, Zhou; Xu, Zhirui; Yang, Zhenwei; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Wen Chao; Zhang, Yanxi; Zhelezov, Alexey; Zhokhov, Anatoly; Zhong, Liang; Zvyagin, Alexander

    2015-02-04

    Using the latest LHCb measurements of time-dependent $C\\!P$ violation in the $B^0_s \\to K^+K^-$ decay, a U-spin relation between the decay amplitudes of $B^0_s \\to K^+K^-$ and $B^0\\to \\pi^+\\pi^-$ decay processes allows constraints to be placed on the angle $\\gamma$ of the unitarity triangle and on the $B^0_s$ mixing phase $-2\\beta_s$. Results from an extended approach, which uses additional inputs on $B^0\\to \\pi^0\\pi^0$ and $B^+\\to \\pi^+\\pi^0$ decays from other experiments and exploits isospin symmetry, are also presented. The dependence of the results on the maximum allowed amount of U-spin breaking is studied. At 68% probability, the value $\\gamma = \\left( 63.5^{\\,+\\, 7.2}_{\\,-\\,6.7} \\right)^\\circ~\\mathrm{modulo}~180^\\circ$ is determined. In an alternative analysis, the value $-2\\beta_s = -0.12 ^{\\,+\\,0.14}_{\\,-\\,0.16}\\,\\,\\mathrm{rad}$ is found. In both measurements, the uncertainties due to U-spin breaking effects up to 50% are included.

  10. High Sensitivity Detection of Xe Isotopes Via Beta-Gamma Coincidence Counting

    International Nuclear Information System (INIS)

    Bowyer, Ted W.; McIntyre, Justin I.; Reeder, Paul L.

    1999-01-01

    Measurement of xenon fission product isotopes is a key element in the global network being established to monitor the Comprehensive Nuclear-Test-Ban Treaty. Pacific Northwest National Laboratory has developed an automated system for separating Xe from air which includes a beta-gamma counting system for 131mXe, 133mXe, 133Xe, and 135Xe. Betas and conversion electrons are detected in a plastic scintillation cell containing the Xe sample. The counting geometry is nearly 100% for beta and conversion electrons. The resolution in the pulse height spectrum from the plastic scintillator is sufficient to observe distinct peaks for specific conversion electrons. Gamma and X-rays are detected in a NaI(Tl) scintillation detector which surrounds the plastic scintillator sample cell. Two-dimensional pulse height spectra of gamma energy versus beta energy are obtained. Each of the four xenon isotopes has a distinctive signature in the two-dimensional energy array. The details of the counting system, examples of two-dimensional beta-gamma data, and operational experience with this counting system will be described

  11. Alpha-beta-gamma spectrometer as an aid in directing decontamination of soils

    International Nuclear Information System (INIS)

    Berger, C.D.

    1981-01-01

    This technique permits rapid assessment of alpha-beta-gamma-emitter contamination in soils at sufficiently low concentrations to direct field operations. Of particular importance is its applicability during initial decommissioning and decontamination surveys when characterization of alpha and beta contamination in the presence of a high gamma background is necessary. This system has not yet been made portable for in-situ use, but it is expected that results willbe favorable when operated as a field instrument, resulting in simplified standard decontamination operation

  12. Solved problems in analysis as applied to gamma, beta, Legendre and Bessel functions

    CERN Document Server

    Farrell, Orin J

    2013-01-01

    Nearly 200 problems, each with a detailed, worked-out solution, deal with the properties and applications of the gamma and beta functions, Legendre polynomials, and Bessel functions. The first two chapters examine gamma and beta functions, including applications to certain geometrical and physical problems such as heat-flow in a straight wire. The following two chapters treat Legendre polynomials, addressing applications to specific series expansions, steady-state heat-flow temperature distribution, gravitational potential of a circular lamina, and application of Gauss's mechanical quadrature

  13. Analysis method for beta-gamma coincidence spectra from radio-xenon isotopes

    International Nuclear Information System (INIS)

    Yang Wenjing; Yin Jingpeng; Huang Xiongliang; Cheng Zhiwei; Shen Maoquan; Zhang Yang

    2012-01-01

    Radio-xenon isotopes monitoring is one important method for the verification of CTBT, what includes the measurement methods of HPGe γ spectrometer and β-γ coincidence. The article describes the analytic flowchart and method of three-dimensional beta-gamma coincidence spectra from β-γ systems, and analyses in detail the principles and methods of the regions of interest of coincidence spectra and subtracting the interference, finally gives the formula of radioactivity of Xenon isotopes and minimum detectable concentrations. Studying on the principles of three-dimensional beta-gamma coincidence spectra, which can supply the foundation for designing the software of β-γ coincidence systems. (authors)

  14. Functions of Beta- and Gamma-Catenins in Prostate Cancer

    National Research Council Canada - National Science Library

    Reed, John

    1999-01-01

    .... We recently discovered that the protein Siah-1 interacts with the APC/catenin complex, and regulates the ubiquitin-dependent turnover of gamma-catenin through a novel previously unidentified mechanism...

  15. Formation of hydrogen fluoride by gamma and beta sterilisation in medical devices containing perfluoroheptane

    International Nuclear Information System (INIS)

    Zuendorf, Josef; Kremer, Stefan; Grueger, Thomas

    2008-01-01

    Infusion of hexadecafluoroheptane, a liquid perfluorocarbon released from repaired Althane dialysers was found to be the most probable reason for the deaths of 53 dialysis patients reported in the year 2001. This study focuses on toxic decomposition products generated due to gamma and beta sterilisation of hexadecafluoroheptane. The responsible dialysers were sterilised with a maximum dose of 45 kGy gamma irradiation. We investigated the influence of both 20-500 kGy gamma and beta irradiation on perfluoroheptane. Analysis of the irradiated samples verified the decomposition of perfluoroheptane in dependence on the dose of irradiation. Beta irradiation resulted in a higher degree of decomposition than the same dose of gamma irradiation. As decomposition products, hydrogen fluoride, CO 2 , and one saturated fluorinated hydrocarbon which could not be analysed exactly were identified. Even at 20 kGy gamma irradiation hydrogen fluoride was detectable. Our results provide evidence that hydrogen fluoride is generated as a highly toxic decomposition product when perfluoroheptane is sterilised with gamma irradiation as it was applied on the affected dialysers. There is no evidence of other toxic degradation products especially perfluoroisobutylene. Therefore, hydrogen fluoride or the dissociated fluoride ions might act as a toxic agent when medical devices containing liquid perfluorocarbons are sterilised by irradiation

  16. Xe isotope detection and discrimination using beta spectroscopy with coincident gamma spectroscopy

    Science.gov (United States)

    Reeder, P. L.; Bowyer, T. W.

    1998-02-01

    Beta spectroscopic techniques show promise of significant improvements for a beta-gamma coincidence counter that is part of a system for analyzing Xe automatically separated from air. The previously developed counting system for 131mXe, 133mXe, 133gXe, and 135gXe can be enhanced to give additional discrimination between these Xe isotopes by using the plastic scintillation sample cell as a beta spectrometer to resolve the conversion electron peaks. The automated system will be a key factor in monitoring the Comprehensive Test Ban Treaty.

  17. Azathioprine versus Beta Interferons for Relapsing-Remitting Multiple Sclerosis: A Multicentre Randomized Non-Inferiority Trial

    Science.gov (United States)

    Massacesi, Luca; Tramacere, Irene; Amoroso, Salvatore; Battaglia, Mario A.; Benedetti, Maria Donata; Filippini, Graziella; La Mantia, Loredana; Repice, Anna; Solari, Alessandra; Tedeschi, Gioacchino; Milanese, Clara

    2014-01-01

    For almost three decades in many countries azathioprine has been used to treat relapsing-remitting multiple sclerosis. However its efficacy was usually considered marginal and following approval of β interferons for this indication it was no longer recommended as first line treatment, even if presently no conclusive direct β interferon-azathioprine comparison exists. To compare azathioprine efficacy versus the currently available β interferons in relapsing-remitting multiple sclerosis, a multicenter, randomized, controlled, single-blinded, non-inferiority trial was conducted in 30 Italian multiple sclerosis centers. Eligible patients (relapsing-remitting course; ≥2 relapses in the last 2 years) were randomly assigned to azathioprine or β interferons. The primary outcome was annualized relapse rate ratio (RR) over 2 years. Key secondary outcome was number of new brain MRI lesions. Patients (n = 150) were randomized in 2 groups (77 azathioprine, 73 β interferons). At 2 years, clinical evaluation was completed in 127 patients (62 azathioprine, 65 β interferons). Annualized relapse rate was 0.26 (95% Confidence Interval, CI, 0.19–0.37) in the azathioprine and 0.39 (95% CI 0.30–0.51) in the interferon group. Non-inferiority analysis showed that azathioprine was at least as effective as β interferons (relapse RRAZA/IFN 0.67, one-sided 95% CI 0.96; p<0.01). MRI outcomes were analyzed in 97 patients (50 azathioprine and 47 β interferons). Annualized new T2 lesion rate was 0.76 (95% CI 0.61–0.95) in the azathioprine and 0.69 (95% CI 0.54–0.88) in the interferon group. Treatment discontinuations due to adverse events were higher (20.3% vs. 7.8%, p = 0.03) in the azathioprine than in the interferon group, and concentrated within the first months of treatment, whereas in the interferon group discontinuations occurred mainly during the second year. The results of this study indicate that efficacy of azathioprine is not inferior to that of

  18. Variation in the binding of 125I-labeled interferon-beta ser to cellular receptors during growth of human renal and bladder carcinoma cells in vitro

    International Nuclear Information System (INIS)

    Ruzicka, F.J.; Schmid, S.M.; Groveman, D.S.; Cummings, K.B.; Borden, E.C.

    1987-01-01

    Studies of various established human bladder and renal carcinoma cell lines cultured in vitro demonstrated the presence of specific, saturable, high affinity binding sites for 125 I-labeled human interferon Beta ser IFN-beta ser). This recombinant produced interferon labeled with approximately one atom of 125 I/molecule of IFN expressed minimal or no loss of antiviral activity. A single class of binding sites (1000-2000/cell) with an affinity constant of 10(10)-10(11) L/M was measured at 4 degrees C for cells exhibiting widely different sensitivity to the antiproliferative effect of IFN-beta ser. Major fluctuations in the binding of 125 I-labeled IFN-beta ser to cellular receptors were observed during in vitro proliferation of four of five cell lines examined. A significant decrease (P less than 0.001) in specific binding was observed 48 h after cultures were established. Cell cycle analysis suggested that within the first 24 h and in the very late log and stationary phase of growth of ACHN (human renal carcinoma) cells, variations in the binding of 125 I-labeled IFN-beta ser were partially attributable to binding fluctuations during the mitotic cycle. The 2- to 3-fold decline 24 h following plating of ACHN cells corresponded to a 70% decrease in the number of cells in G0-G1. T24 (human transitional cell carcinoma) and ACHN cells, synchronized by serum starvation, demonstrated increased binding of 125 I-labeled IFN-beta ser 4-16 h following serum replenishment. This increase in receptor binding occurred prior to the onset of DNA and protein synthesis and was followed by a decline immediately prior to cell division. Binding site analysis indicated that the increased binding prior to DNA synthesis was due to a 5- to 6-fold increase in receptor affinity for the radiolabeled ligand

  19. New information on the $\\beta$-decay of $^{11}$Li from Doppler broadened $\\gamma$-lines

    CERN Document Server

    Fynbo, H O U; Cederkäll, J; Courtin, S; Dessagne, P; Jonson, B; Le Scornet, G; Nilsson, T; Nyman, G H; Poirier, E; Riisager, K; Tengblad, O; Wilhelmsen, K

    2004-01-01

    The $\\gamma$-ray spectrum following $\\beta$-decay of $^{11}$Li has been remeasured at the ISOLDE facility at CERN. Two new transitions were observed through the use of large Ge-detectors. Most $\\gamma$-decays will follow P-delayed neutron emission. Information on the energy of the neutron is derived from analysis of the $\\gamma$-line-shape and used to construct a partial decay scheme for $^{11}$Li. Lifetime values for the 1$^{-}$ and 2$^{-}$ levels in $^{10}$Be are also derived. A new partial decay scheme is presented. (43 refs).

  20. Interferon gamma/NADPH oxidase defense system in immunity and cancer

    Czech Academy of Sciences Publication Activity Database

    Hodný, Zdeněk; Reiniš, Milan; Hubáčková, Soňa; Vašicová, Pavla; Bartek, Jiří

    2016-01-01

    Roč. 5, č. 2 (2016), č. článku e1080416. ISSN 2162-402X Institutional support: RVO:68378050 ; RVO:61388971 Keywords : Cellular senescence * DNA damage response * oxidative stress * tumor growth factor beta * tumor immunosurveillance Subject RIV: EB - Genetics ; Molecular Biology; EC - Immunology (MBU-M) Impact factor: 7.719, year: 2016

  1. Effect of the gamma radiation of cobalt 60 on the beta carotids present in the carrot

    International Nuclear Information System (INIS)

    Perez Lopez, Sergio Victor Hugo

    1997-01-01

    In the present work it was investigated the effect of the gamma radiation of cobalt 60 on the beta carotid's in the carrot (daucus carota), using for it three different radiation dose (100, 150 and 200 kilo-rad) and analyzing them by means of the liquid chromatography technique of high resolution (HPLC)

  2. The influence of interleukin-1beta on gamma-glutamyl transpeptidase activity in rat hippocampus

    Czech Academy of Sciences Publication Activity Database

    Kaiser, M.; Mareš, Vladislav; Šťastný, František; Bubeníková-Valešová, V.; Lisá, Věra; Suchomel, P.; Balcar, V. J.

    2006-01-01

    Roč. 55, č. 4 (2006), s. 461-465 ISSN 0862-8408 R&D Projects: GA MZd(CZ) NF7626 Institutional research plan: CEZ:AV0Z50110509 Keywords : interleukin-1beta * gamma- glutamyltranspeptidase * hippocampus Subject RIV: ED - Physiology Impact factor: 2.093, year: 2006

  3. On k-Gamma and k-Beta Distributions and Moment Generating Functions

    Directory of Open Access Journals (Sweden)

    Gauhar Rahman

    2014-01-01

    Full Text Available The main objective of the present paper is to define k-gamma and k-beta distributions and moments generating function for the said distributions in terms of a new parameter k>0. Also, the authors prove some properties of these newly defined distributions.

  4. Development of Simultaneous Beta-and-Coincidence-Gamma Imager for Plant Imaging Research

    Energy Technology Data Exchange (ETDEWEB)

    Tai, Yuan-Chuan [Washington Univ., St. Louis, MO (United States). School of Medicine

    2016-09-30

    The goal of this project is to develop a novel imaging system that can simultaneously acquire beta and coincidence gamma images of positron sources in thin objects such as leaves of plants. This hybrid imager can be used to measure carbon assimilation in plants quantitatively and in real-time after C-11 labeled carbon-dioxide is administered. A better understanding of carbon assimilation, particularly under the increasingly elevated atmospheric CO2 level, is extremely critical for plant scientists who study food crop and biofuel production. Phase 1 of this project is focused on the technology development with 3 specific aims: (1) develop a hybrid detector that can detect beta and gamma rays simultaneously; (2) develop an imaging system that can differentiate these two types of radiation and acquire beta and coincidence gamma images in real-time; (3) develop techniques to quantify radiotracer distribution using beta and gamma images. Phase 2 of this project is to apply technologies developed in phase 1 to study plants using positron-emitting radionuclide such as 11C to study carbon assimilation in biofuel plants.

  5. ORNL shielded facilities capable of remote handling of highly radioactive beta--gamma emitting materials

    International Nuclear Information System (INIS)

    Whitson, W.R.

    1977-09-01

    A survey of ORNL facilities having adequate shielding and containment for the remote handling of experimental quantities of highly radioactive beta-gamma emitting materials is summarized. Portions of the detailed descriptions of these facilities previously published in ORNL/TM-1268 are still valid and are repeated

  6. Selective Beta and Gamma-ray Discrimination by CdWO{sub 4} and PlasticScintillator

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Jun Woo; Kim, Hee Reyoung [Dept. of Nuclear Engineering, Ulsan National Institute of Science and Technology, Ulsan (Korea, Republic of)

    2017-04-15

    Radiation monitoring technique has been used for monitoring of decommissioning site of nuclear facility, radioactive waste disposal site, or in case of radioactivity accident. For rapid measurement of gamma-ray and beta-ray, many portable radiation detectors were developed but they are sensitive to specific radiation type. For example, portable detectors using NaI(Tl) or high purity germanium (HPGe) are suitable to detect gamma-ray. Otherwise, Geiger-müller (GM) tube or ionization chamber are suitable to detect all-types of radiation but it is hard to determine which particle is detected in the detector. In this reason, phoswich detectors for discrimination of beta-ray and gamma-ray were developed by using pulse shape discrimination. In this study, another approach to discriminate the beta-ray and gamma-ray is carried out. Two scintillators are used, cadmium tungstate (CdWO{sub 4}) and plastic scintillator. They have huge difference in their effective atomic number and mass density, thus they have huge difference in their gamma-ray sensitivity while the sensitivity of beta-ray is similar. The characterization of beta-ray and gamma-ray discrimination by using this characteristics is include. A technique of discrimination between beta-ray and gamma-ray was suggested. The method was verified by Monte Carlo simulation and experiment. This work showed feasibility on in field measurement of radiation with discrimination of beta-ray and gamma-ray.

  7. {beta}-{gamma} systems and the deformations of the BRST operator

    Energy Technology Data Exchange (ETDEWEB)

    Zeitlin, Anton M [Department of Mathematics, Yale University, 442 Dunham Lab, 10 Hillhouse Ave, New Haven, CT 06511 (United States)], E-mail: anton.zeitlin@yale.edu

    2009-09-04

    We describe the relation between simple logarithmic CFTs associated with closed and open strings, and their 'infinite metric' limits, corresponding to the {beta}-{gamma} systems. This relation is studied on the level of the BRST complex: we show that the consideration of metric as a perturbation leads to a certain deformation of the algebraic operations of the Lian-Zuckerman type on the vertex algebra, associated with the {beta}-{gamma} systems. The Maurer-Cartan equations corresponding to this deformed structure in the quasi-classical approximation lead to the nonlinear field equations. As an explicit example, we demonstrate that using this construction, Yang-Mills equations can be derived. This gives rise to a nontrivial relation between the Courant-Dorfman algebroid and homotopy algebras emerging from the gauge theory. We also discuss a possible algebraic approach to the study of beta-functions in sigma-models.

  8. Determination of gross gamma and gross beta activities in liquid effluent samples. Phase I

    International Nuclear Information System (INIS)

    Curtis, K.E.; Sood, S.P.

    1985-08-01

    Several inadequacies in the presently used procedures for gross gamma and gross beta measurements in aqueous wastes have been identified. Both the presence of suspended particulate activity and the use of cesium-137 as a calibration standard can cause gross gamma measurements to overestimate the actual activity in the sample. At the same time, sample preparation for the determination of gross beta activities causes large losses of radioiodine before the measurement step and the presence of solid material can cause a serious decrease in the beta counting efficiency. A combination of these errors could result in large discrepancies between the results obtained by the two measurement methods. Improved procedures are required to overcome these problems

  9. Successful Application of the Gamma-Interferon Assay in a Bovine Tuberculosis Eradication Program: The French Bullfighting Herd Experience.

    Science.gov (United States)

    Keck, Nicolas; Boschiroli, Maria-Laura; Smyej, Florence; Vogler, Valérie; Moyen, Jean-Louis; Desvaux, Stéphanie

    2018-01-01

    In the French Camargue region, where bovine tuberculosis had been enzootic for several years in bullfighting cattle herds, the gamma-interferon (IFN) assay was used since 2003 in parallel with the intradermal test in order to increase overall disease detection sensitivity in infected herds. This study presents the results of a field-evaluation of the assay during a 10-year period (2004-2014) of disease control and surveillance program and explores the particular pattern of IFN assay results in bullfight herds in comparison to cattle from other regions of France. The low sensitivity [59.2% (50.6; 67.3)] of IFN assay using the tuberculin stimulation could be related to the poor gamma-IFN production from bullfight cattle blood cells which is significantly lower than in animals of conventional breeds. The characteristics of the assay were progressively adapted to the epidemiological situation and the desired strategic applications. Data analysis with a receiver operating characteristic curve based on a simple S/P value algorithm allowed for the determination of a new cutoff adapted for a global screening, giving a high specificity of 99.9% results and a high accuracy of the assay. Having regularly risen to above 5% since 2005, with a peak around 10% in 2010, the annual incidence dropped to under 1% in 2014. The positive predictive value relative to the bacteriological confirmation evolved during the years, from 33% in 2009 to 12% during the last screening period, a normal trend in a context of decreasing prevalence. The estimated rate of false-positive reactions during screening campaigns was 0.67%, confirming the high specificity of the test, measured in bTB negative herds, in this epidemiological context. The proportion of false-positive reactions decreased with the age and was higher in males than in females. Although these results indicate that the IFN assay is accurate in the field, it also emphasizes great differences between interferon quantities produced by

  10. Pilot study of whole-blood gamma interferon response to the Vibrio cholerae toxin B subunit and resistance to enterotoxigenic Escherichia coli-associated diarrhea.

    Science.gov (United States)

    Flores, Jose; DuPont, Herbert L; Paredes-Paredes, Mercedes; Aguirre-Garcia, M Magdalena; Rojas, Araceli; Gonzalez, Alexei; Okhuysen, Pablo C

    2010-05-01

    Enterotoxigenic Escherichia coli (ETEC), which produces heat-labile toxin (LT), is a common cause of travelers' diarrhea (TD). The B subunit of ETEC LT is immunologically related to the B subunit of Vibrio cholerae toxin (CT). In this pilot study we evaluated the whole-blood gamma interferon response to CT B in 17 U.S. adults traveling to Mexico. Only one of nine subjects who demonstrated a cellular immune response as determined by whole-blood gamma interferon production to CT B on arrival to Mexico developed diarrhea, whereas five of eight without a cellular response developed diarrhea. Markers of the cellular immune response to ETEC LT could help in identifying individuals immune to ETEC LT, and these markers deserve additional study.

  11. Standardization of 56Co had been carried out using 4 pi beta-gamma coincidence methods

    International Nuclear Information System (INIS)

    Wardiyanto, Gatot; Pujadi

    2000-01-01

    Standardization of exp.56 Co had been carried out using 4 pi beta-gamma coincidence methods. The radionuclide use for calibration of nuclear instruments on range of energy over 1500 keV. The exp.56 Co had been produced by irradiation of proton by using a cyclotron with 15 MeV of energy and 300 mb of cross-section to natural iron target (99,5% of purity) at the Institute for Nuclear Study, University of Tokyo. Source preparation had been done by gravimetry method after the irradiated source was dissolved in 8N HCI solution. The disintegration rate had been measured using 4 pi beta-gamma coincidence apparatus, where the gamm gets sets on 511 and 847 keV gamma-rays. The result measurement is fairly good with the specific activity is 3078 n 15 Bq/mg

  12. Change in the aldolase activity in rats' hearts after irradiation with. gamma. and. beta. rays

    Energy Technology Data Exchange (ETDEWEB)

    Kukulyanskaya, M F; Borodina, G N

    1973-01-01

    The activity of aldolase fructoso-1-phosphate (I) and aldolase fructoso-1, 6-diphosphate (II) has been studied at various periods after total ..gamma.. and ..beta.. irradiation of rats at a dose of 42 rads. It has been shown that after ..gamma.. irradiation the activity of I increases in the supernatant liquid of the heart muscle homogenate, but drops sharply in the nuclei. In total, the activity of the homogenate did not change. The activity of II dropped for seven days, and after 1 hour and 30 days it was above the normal level. After ..beta.. radiation the activity of II is slowed down after 1, 7, and 15 days. These changes occur in all subcellular fractions. The authors note that the changes in the activity of aldolases are more sharply demarcated after ..gamma.. irradiation and are more substantial for II. (JPRS)

  13. Thermodynamics in Gliomas: Interactions between the Canonical WNT/Beta-Catenin Pathway and PPAR Gamma

    Directory of Open Access Journals (Sweden)

    Alexandre Vallée

    2017-05-01

    Full Text Available Gliomas cells are the site of numerous metabolic and thermodynamics abnormalities with an increasing entropy rate which is characteristic of irreversible processes driven by changes in Gibbs energy, heat production, intracellular acidity, membrane potential gradient, and ionic conductance. We focus our review on the opposing interactions observed in glioma between the canonical WNT/beta-catenin pathway and PPAR gamma and their metabolic and thermodynamic implications. In gliomas, WNT/beta-catenin pathway is upregulated while PPAR gamma is downregulated. Upregulation of WNT/beta-catenin signaling induces changes in key metabolic enzyme that modify their thermodynamics behavior. This leads to activation pyruvate dehydrogenase kinase 1(PDK-1 and monocarboxylate lactate transporter 1 (MCT-1. Consequently, phosphorylation of PDK-1 inhibits pyruvate dehydrogenase complex (PDH. Thus, a large part of pyruvate cannot be converted into acetyl-CoA in mitochondria and in TCA (tricarboxylic acid cycle. This leads to aerobic glycolysis despite the availability of oxygen, named Warburg effect. Cytoplasmic pyruvate is, in major part, converted into lactate. The WNT/beta-catenin pathway induces also the transcription of genes involved in cell proliferation, cell invasiveness, nucleotide synthesis, tumor growth, and angiogenesis, such as c-Myc, cyclin D1, PDK. In addition, in gliomas cells, PPAR gamma is downregulated, leading to a decrease in insulin sensitivity and an increase in neuroinflammation. Moreover, PPAR gamma contributes to regulate some key circadian genes. Abnormalities in the regulation of circadian rhythms and dysregulation in circadian clock genes are observed in gliomas. Circadian rhythms are dissipative structures, which play a key role in far-from-equilibrium thermodynamics through their interactions with WNT/beta-catenin pathway and PPAR gamma. In gliomas, metabolism, thermodynamics, and circadian rhythms are tightly interrelated.

  14. Loci controlling lymphocyte production of interferon gamma after alloantigen stimulation in vitro and their co-localization with genes controlling lymphocyte infiltration of tumors and tumor susceptibility

    Czech Academy of Sciences Publication Activity Database

    Lipoldová, Marie; Havelková, Helena; Badalová, Jana; Vojtíšková, Jarmila; Quan, L.; Krulová, Magdalena; Sohrabi, Yahya; Stassen, A. P. M.; Demant, P.

    2010-01-01

    Roč. 59, č. 2 (2010), s. 203-213 ISSN 0340-7004 R&D Projects: GA MŠk(CZ) LC06009; GA AV ČR IAA500520606; GA ČR GD310/08/H077 Institutional research plan: CEZ:AV0Z50520514 Keywords : Tumor susceptibility * Genetic control of interferon gamma production * Lymphocyte infiltration of tumors Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.293, year: 2010

  15. Association of Monoclonal Expansion of Epstein-Barr Virus-Negative CD158a+ NK Cells Secreting Large Amounts of Gamma Interferon with Hemophagocytic Lymphohistiocytosis▿

    Science.gov (United States)

    López-Álvarez, María R.; Martínez-Sánchez, María V.; Salgado-Cecilia, María G.; Campillo, José A.; Heine-Suñer, Damian; Villar-Permuy, Florentina; Fuster, José L.; Bas, Águeda; Gil-Herrera, Juana; Muro, Manuel; García-Alonso, Ana M.; Álvarez-López, María R.; Minguela, Alfredo

    2009-01-01

    We report the first case of hemophagocytic lymphohistiocytosis (HLH) induced by the monoclonal expansion of Epstein-Barr virus (EBV)-negative NK cells. Consanguinity of the patient's parents made it necessary to discard familial HLH in the patient and her sister with identical HLA markers and demonstrate that no cause other than the expansion of NK cells, which secrete high levels of gamma interferon, was inducing HLH in this patient. PMID:19020108

  16. Comparison of tumour and metastases radioimmunodetection in adenocarcinomas between patients with and without immunomodulation with interferon gamma using In-111 labelled anti-TAG-72-antibody

    International Nuclear Information System (INIS)

    Becherer, A.; Virgolini, I.; Kletter, M.; Raderer, M.; Scheithauer, W.

    1994-01-01

    Radioimmunodetection depends on antigen expression of malignant tissue against which radiolabelled antibodies are directed. Since gamma-interferon (IFNg) has been shown to enhance tumor-associated antigen-72 (TAG-72) expression on cell surfaces of colorectal carcinomas, it is compared anti-TAG-72 imaging before and after IFNg treatment. It is found an improved diagnostic accuracy concerning both primary and metastic tumours by imaging under IFNg-therapy and conclude that immunomodulation may increase the diagnostic value of immunoscintigraphy

  17. Counting efficiency for radionuclides decaying by beta and gamma-ray emission; Calculo de la eficiencia de recuento de nucleidos que experimentan desintegracion beta y desexcitacion gamma simple

    Energy Technology Data Exchange (ETDEWEB)

    Grau, A.; Garcia-Torano, E.

    1988-07-01

    In this paper, counting efficiency vs figure of merit for beta and gamma-ray emitters has been computed. It is assumed that the decay scheme has only a gamma level and the beta-ray emission may be coincident with the gamma-rays or the internal-conversion electrons. The radionuclides tabulated are: 20 {sub 0}, 20{sub p}, 28{sub A}l, 35{sub p}, 41{sub A}r, 42{sub K}, 47{sub S}e, 62{sub F}e, 66{sub C}u, 81{sub G}e, 86{sub B}b, 108{sub R}u, 112{sub p}d, 121{sub S}n(Ni), 122{sub I}n, 129{sub I}, 141{sub C}e 171{sub T}m, 194{sub O}s, 2O3{sub H}g, 205{sub H}g, 210{sub p}b, 225{sub R}a, 142{sub p}r, 151{sub S}m, 244{sub A}m(m). It has been assumed that the liquid is a toluene based scintillator solution in standard glass vials containing 10 cm''3. (Author) 8 refs.

  18. Role of interferon in resistance and immunity to protozoa

    Science.gov (United States)

    Sonnenfeld, G.; Degee, A. L. W.; Mansfield, J. M.; Newsome, A. L.; Arnold, R. R.

    1985-01-01

    Production of interferon (I) in response to protozoan infection, and the interferon-mediated inhibition of parasite replication were studied in order to determine if these effects may be related to immunologic-mediated resistance of the hosts. Two extracellular parasites-Trypanosoma brucei rhodesiense and Naegleria fowlei were used. Upon infection with the trypanosome, only resistant strains of mice produced I. An early peak of alpha/beta I is followed by appearance of gamma I, which coincided with antibody production and a drop in parasitemia. In case of the amoeba, pretreatment of its suspension with alpha/beta I inhibits its replication in vitro, and appears to protect mice from the infection and the disease. It is proposed that production of interferon, with its regulatory effect on the immune responses, may play a major role in regulating the processes of protozoan-caused diseases.

  19. Simultaneous and separate, low background counting of beta rays and gamma rays using the phoswich principle

    International Nuclear Information System (INIS)

    Mayhugh, M.R.; Utts, B.K.; Shoffner, B.M.

    1978-01-01

    A phoswich constructed using thin calcium fluoride optically coupled to a thicker sodium iodide crystal and operated with pulse shape analysis equipment can be used as an efficient low background counting assembly. Low background in the beta ray counting channel is achieved by judicious choice of pure materials in the assembly and by operating the analysis equipment so as to reject background events which occur simultaneously in the sodium iodide crystal. Careful survey of construction materials and methods has resulted in reducing beta ray counting background to 0.6 c/min for a 2-inch diameter assembly. The radioactivity of typical building materials will be discussed. A pulse shape analyzer has been constructed which provides separately adjusted time windows and separate output information for the beta ray and gamma ray channels. The dual channel capability combined with the low beta ray background reduces the sample counting time significantly for typical laboratory samples. (author)

  20. Serum profile of cytokines interferon gamma and interleukin-10 in ewes subjected to artificial insemination by cervical retraction.

    Science.gov (United States)

    Alvares, C T G; Cruz, J F; Romano, C C; Brandão, F Z

    2016-04-15

    This study evaluated the influence of artificial insemination (AI) by cervical retraction (CRI) on serum levels of interferon gamma (IFNγ) and interleukin-10 (IL-10) in ewes. Synchronized pluriparous Santa Inês ewes were subjected to natural mating (NM, n = 8) and AI, which was performed for a fixed time (55 ± 1 hour) by CRI (n = 8) or laparoscopy (n = 8). Ewes were classified as pregnant, with return to estrus (RE) or with embryonic loss (EL). Blood samples were collected on Day 0, Day 3, Day 5, Day 12, and Day 17 (Day 0 = AI/NM) for progesterone dosage and cytokines were quantified from Day 0 to Day 12. Progesterone levels were constant, except for a decrease in ewes with RE at Day 17 (P ewes with EL had lower serum levels of IFNγ and IL-10 than pregnant ewes and ewes with RE, regardless of the reproductive method used, with averages of 769.1, 714.9, and 555.7 pg/mL for IFNγ and 713.8, 699.3, and 578.7 pg/mL for IL-10 in pregnant ewes, ewes with RE and EL, respectively (P ewes does not alter the profile of serum cytokines IFNγ and IL-10 and does not induce an inflammatory reaction that can compromise pregnancy. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Interferon-gamma improves impaired dentinogenic and immunosuppressive functions of irreversible pulpitis-derived human dental pulp stem cells

    Science.gov (United States)

    Sonoda, Soichiro; Yamaza, Haruyoshi; Ma, Lan; Tanaka, Yosuke; Tomoda, Erika; Aijima, Reona; Nonaka, Kazuaki; Kukita, Toshio; Shi, Songtao; Nishimura, Fusanori; Yamaza, Takayoshi

    2016-01-01

    Clinically, irreversible pulpitis is treated by the complete removal of pulp tissue followed by replacement with artificial materials. There is considered to be a high potential for autologous transplantation of human dental pulp stem cells (DPSCs) in endodontic treatment. The usefulness of DPSCs isolated from healthy teeth is limited. However, DPSCs isolated from diseased teeth with irreversible pulpitis (IP-DPSCs) are considered to be suitable for dentin/pulp regeneration. In this study, we examined the stem cell potency of IP-DPSCs. In comparison with healthy DPSCs, IP-DPSCs expressed lower colony-forming capacity, population-doubling rate, cell proliferation, multipotency, in vivo dentin regeneration, and immunosuppressive activity, suggesting that intact IP-DPSCs may be inadequate for dentin/pulp regeneration. Therefore, we attempted to improve the impaired in vivo dentin regeneration and in vitro immunosuppressive functions of IP-DPSCs to enable dentin/pulp regeneration. Interferon gamma (IFN-γ) treatment enhanced in vivo dentin regeneration and in vitro T cell suppression of IP-DPSCs, whereas treatment with tumor necrosis factor alpha did not. Therefore, these findings suggest that IFN-γ may be a feasible modulator to improve the functions of impaired IP-DPSCs, suggesting that autologous transplantation of IFN-γ-accelerated IP-DPSCs might be a promising new therapeutic strategy for dentin/pulp tissue engineering in future endodontic treatment. PMID:26775677

  2. Innate invariant NKT cells recognize Mycobacterium tuberculosis-infected macrophages, produce interferon-gamma, and kill intracellular bacteria.

    Directory of Open Access Journals (Sweden)

    Isabel Sada-Ovalle

    2008-12-01

    Full Text Available Cellular immunity to Mycobacterium tuberculosis (Mtb requires a coordinated response between the innate and adaptive arms of the immune system, resulting in a type 1 cytokine response, which is associated with control of infection. The contribution of innate lymphocytes to immunity against Mtb remains controversial. We established an in vitro system to study this question. Interferon-gamma is produced when splenocytes from uninfected mice are cultured with Mtb-infected macrophages, and, under these conditions, bacterial replication is suppressed. This innate control of bacterial replication is dependent on CD1d-restricted invariant NKT (iNKT cells, and their activation requires CD1d expression by infected macrophages as well as IL-12 and IL-18. We show that iNKT cells, even in limiting quantities, are sufficient to restrict Mtb replication. To determine whether iNKT cells contribute to host defense against tuberculosis in vivo, we adoptively transferred iNKT cells into mice. Primary splenic iNKT cells obtained from uninfected mice significantly reduce the bacterial burden in the lungs of mice infected with virulent Mtb by the aerosol route. Thus, iNKT cells have a direct bactericidal effect, even in the absence of synthetic ligands such as alpha-galactosylceramide. Our finding that iNKT cells protect mice against aerosol Mtb infection is the first evidence that CD1d-restricted NKT cells mediate protection against Mtb in vivo.

  3. The role of interferon gamma release assays in the monitoring of response to anti-tuberculosis treatment in children.

    Science.gov (United States)

    Shaik, Junaid; Pillay, Manormoney; Jeena, Prakash

    2014-09-01

    Successful control of childhood TB requires early diagnosis, effective chemotherapy and a method of evaluating the response to therapy. Identification of suitable biomarkers that predict the response to anti-TB therapy may allow the duration of treatment to be shortened. The majority of biomarker studies in paediatric TB have focused on the role of T cell-based interferon-gamma (IFN-γ) release assays (IGRAs) in the diagnosis of either latent or active disease. Little has been published on the role of IGRAs in the monitoring response to therapy in children. We reviewed the available literature to ascertain the value of IGRAs in the monitoring of response to anti-TB therapy in children. We explored the results of the few studies that have investigated the role of IGRAs as markers of response to anti-TB treatment in children. We conclude that the role of IGRAs as surrogate markers appears promising. Robust clinical trials are, however, needed to entrench the value of IGRAs as surrogate biomarkers of response to anti-TB therapy in children. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. The Effect of Levothyroxine on Serum Levels of Interleukin 10 and Interferon-gamma in Rat Model of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Cobra Payghani

    2017-01-01

    Full Text Available Background: There is an increase in inflammatory and a reduction in anti-inflammatory cytokines in multiple sclerosis (MS. Considering the role of thyroid hormones in the development and regulation of both neural and immune systems, the aim of this study was to evaluate the effects of levothyroxine on serum concentrations of interleukin-10 (IL-10 and interferon gamma (IFN-γ in animal models of MS. Materials and Methods: To induce demyelination in male Wistar rats, lysolecithin was injected into the optic chiasm. Then levothyroxine was injected intraperitoneally (20, 50, and 100 μg/kg for 21 days. Serum levels of cytokines were measured by enzyme-linked immunosorbent assay at 7, 14, and 21 days after that. Results: The results showed that injection of lysolecithin to the optic chiasm only increased serum concentrations of IL-10 compared to the sham group (P < 0.05 at 7th day, but this increase was prevented by all doses of levothyroxine. IFN-γ was decreased significantly (P < 0.001 21 days after. Comparing to the sham group at all sampling time and with respect to the MS group at the days 7 and 21, levothyroxine decreased serum concentrations of IFN-γ significantly. Conclusion: The results showed that thyroid hormones probably could produce protective effects against induced demyelination through affecting immune responses.

  5. The Tat protein of human immunodeficiency virus-1 enhances hepatitis C virus replication through interferon gamma-inducible protein-10

    Directory of Open Access Journals (Sweden)

    Qu Jing

    2012-04-01

    Full Text Available Abstract Background Co-infection with human immunodeficiency virus-1 (HIV-1 and hepatitis C virus (HCV is associated with faster progression of liver disease and an increase in HCV persistence. However, the mechanism by which HIV-1 accelerates the progression of HCV liver disease remains unknown. Results HIV-1/HCV co-infection is associated with increased expression of interferon gamma-induced protein-10 (IP-10 mRNA in peripheral blood mononuclear cells (PBMCs. HCV RNA levels were higher in PBMCs of patients with HIV-1/HCV co-infection than in patients with HCV mono-infection. HIV-1 Tat and IP-10 activated HCV replication in a time-dependent manner, and HIV-1 Tat induced IP-10 production. In addition, the effect of HIV-1 Tat on HCV replication was blocked by anti-IP-10 monoclonal antibody, demonstrating that the effect of HIV-1 Tat on HCV replication depends on IP-10. Taken together, these results suggest that HIV-1 Tat protein activates HCV replication by upregulating IP-10 production. Conclusions HIV-1/HCV co-infection is associated with increased expression of IP-10 mRNA and replication of HCV RNA. Furthermore, both HIV-1 Tat and IP-10 activate HCV replication. HIV-1 Tat activates HCV replication by upregulating IP-10 production. These results expand our understanding of HIV-1 in HCV replication and the mechanism involved in the regulation of HCV replication mediated by HIV-1 during co-infection.

  6. Evaluation of pre- and posttransplantation serum interferon-gamma and soluble CD30 for predicting liver allograft rejection.

    Science.gov (United States)

    Kim, K H; Oh, E-J; Jung, E-S; Park, Y-J; Choi, J Y; Kim, D-G; Lee, K Y; Kang, C S

    2006-06-01

    The aim of the present study was to identify whether the serum interferon-gamma (IFNgamma), a Th1 cytokine, or soluble CD30 (sCD30), a marker for activation of Th2 cytokine-producing T cells, predict acute cellular rejection episodes among liver graft patients. Pretransplant and posttransplant sera from 32 living donor liver transplant recipients obtained on days 1, 3, and 7 after surgery were tested for serum IFNgamma and sCD30 concentrations using commercial enzyme-linked immunosorbent assay kits. Recipients with an acute rejection episode (ARE) (n=14) displayed significantly higher IFNgamma concentrations pretransplant than did the patients with no ARE (n=18) (PsCD30 were not different between the non-ARE and ARE groups. However, in comparison with the non-ARE group, who showed steadily decreasing serum sCD30 levels after transplantation, 12 among the 14 patients in the ARE group showed increasing sCD30 levels from day 1 to day 3 after transplantation (PsCD30 increment during the early period after liver transplantation affects the immune response of rejection. This observation emphasizes the clinical relevance of serum sCD30, in addition to serum IFNgamma, as predictive markers for acute liver graft rejection.

  7. Consistency of Mycobacterium tuberculosis-Specific Interferon-Gamma Responses in HIV-1-Infected Women during Pregnancy and Postpartum

    Directory of Open Access Journals (Sweden)

    Sasi R. Jonnalagadda

    2012-01-01

    Full Text Available Background. We determined the consistency of positive interferon-gamma (IFN-γ release assays (IGRAs to detect latent TB infection (LTBI over one-year postpartum in HIV-1-infected women. Methods. Women with positive IGRAs during pregnancy had four 3-monthly postpartum IGRAs. Postpartum change in magnitude of IFN-γ response was determined using linear mixed models. Results. Among 18 women with positive pregnancy IGRA, 15 (83% had a subsequent positive IGRA; 9 (50% were always positive, 3 (17% were always negative, and 6 (33% fluctuated between positive and negative IGRAs. Women with pregnancy IGRA IFN-γ >8 spot forming cells (SFCs/well were more likely to have consistent postpartum IGRA response (odds ratio: 10.0; 95% confidence interval (CI: 0.9–117.0. Change in IFN-γ response over postpartum was 10.2 SFCs/well (95% CI: −1.5–21.8 SFCs/well. Conclusion. Pregnancy positive IGRAs were often maintained postpartum with increased consistency in women with higher baseline responses. There were modest increases in magnitude of IGRA responses postpartum.

  8. Interferon-gamma improves impaired dentinogenic and immunosuppressive functions of irreversible pulpitis-derived human dental pulp stem cells.

    Science.gov (United States)

    Sonoda, Soichiro; Yamaza, Haruyoshi; Ma, Lan; Tanaka, Yosuke; Tomoda, Erika; Aijima, Reona; Nonaka, Kazuaki; Kukita, Toshio; Shi, Songtao; Nishimura, Fusanori; Yamaza, Takayoshi

    2016-01-18

    Clinically, irreversible pulpitis is treated by the complete removal of pulp tissue followed by replacement with artificial materials. There is considered to be a high potential for autologous transplantation of human dental pulp stem cells (DPSCs) in endodontic treatment. The usefulness of DPSCs isolated from healthy teeth is limited. However, DPSCs isolated from diseased teeth with irreversible pulpitis (IP-DPSCs) are considered to be suitable for dentin/pulp regeneration. In this study, we examined the stem cell potency of IP-DPSCs. In comparison with healthy DPSCs, IP-DPSCs expressed lower colony-forming capacity, population-doubling rate, cell proliferation, multipotency, in vivo dentin regeneration, and immunosuppressive activity, suggesting that intact IP-DPSCs may be inadequate for dentin/pulp regeneration. Therefore, we attempted to improve the impaired in vivo dentin regeneration and in vitro immunosuppressive functions of IP-DPSCs to enable dentin/pulp regeneration. Interferon gamma (IFN-γ) treatment enhanced in vivo dentin regeneration and in vitro T cell suppression of IP-DPSCs, whereas treatment with tumor necrosis factor alpha did not. Therefore, these findings suggest that IFN-γ may be a feasible modulator to improve the functions of impaired IP-DPSCs, suggesting that autologous transplantation of IFN-γ-accelerated IP-DPSCs might be a promising new therapeutic strategy for dentin/pulp tissue engineering in future endodontic treatment.

  9. Private sector tuberculosis prevention in the US: Characteristics associated with interferon-gamma release assay or tuberculin skin testing.

    Science.gov (United States)

    Stockbridge, Erica L; Miller, Thaddeus L; Carlson, Erin K; Ho, Christine

    2018-01-01

    To determine whether latent tuberculosis infection risk factors are associated with an increased likelihood of latent tuberculosis infection testing in the US private healthcare sector. A national sample of medical and pharmacy claims representing services rendered January 2011 through December 2013 for 3,997,986 commercially insured individuals in the US who were 0 to 64 years of age. We used multivariable logistic regression models to determine whether TB/LTBI risk factors were associated with an increased likelihood of Interferon-Gamma Release Assay (IGRA) or Tuberculin Skin Test (TST) testing in the private sector. 4.31% (4.27-4.34%) received at least one TST/IGRA test between 2011 and 2013 while 1.69% (1.67-1.72%) received a TST/IGRA test in 2013. Clinical risk factors associated with a significantly increased likelihood of testing included HIV, immunosuppressive therapy, exposure to tuberculosis, a history of tuberculosis, diabetes, tobacco use, end stage renal disease, and alcohol use disorder. Other significant variables included gender, age, asthma, the state tuberculosis rate, population density, and percent of foreign-born persons in a county. Private sector TST/IGRA testing is not uncommon and testing varies with clinical risk indicators. Thus, the private sector can be a powerful resource in the fight against tuberculosis. Analyses of administrative data can inform how best to leverage private sector healthcare toward tuberculosis prevention activities.

  10. Molecular characterisation and expression analysis of interferon gamma in response to natural Chlamydia infection in the koala, Phascolarctos cinereus.

    Science.gov (United States)

    Mathew, Marina; Pavasovic, Ana; Prentis, Peter J; Beagley, Kenneth W; Timms, Peter; Polkinghorne, Adam

    2013-09-25

    Interferon gamma (IFNγ) is a key Th1 cytokine, with a principal role in the immune response against intracellular organisms such as Chlamydia. Along with being responsible for significant morbidity in human populations, Chlamydia is also responsible for wide spread infection and disease in many animal hosts, with reports that many Australian koala subpopulations are endemically infected. An understanding of the role played by IFNγ in koala chlamydial diseases is important for the establishment of better prophylactic and therapeutic approaches against chlamydial infection in this host. A limited number of IFNγ sequences have been published from marsupials and no immune reagents to measure expression have been developed. Through preliminary analysis of the koala transcriptome, we have identified the full coding sequence of the koala IFNγ gene. Transcripts were identified in spleen and lymph node tissue samples. Phylogenetic analysis demonstrated that koala IFNγ is closely related to other marsupial IFNγ sequences and more distantly related to eutherian mammals. To begin to characterise the role of this important cytokine in the koala's response to chlamydial infection, we developed a quantitative real time PCR assay and applied it to a small cohort of koalas with and without active chlamydial disease, revealing significant differences in expression patterns between the groups. Description of the IFNγ sequence from the koala will not only assist in understanding this species' response to its most important pathogen but will also provide further insight into the evolution of the marsupial immune system. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Assessment of safety and interferon gamma responses of Mycobacterium bovis BCG vaccine in goat kids and milking goats.

    Science.gov (United States)

    Pérez de Val, Bernat; Vidal, Enric; López-Soria, Sergio; Marco, Alberto; Cervera, Zoraida; Martín, Maite; Mercader, Irene; Singh, Mahavir; Raeber, Alex; Domingo, Mariano

    2016-02-10

    Vaccination of domestic animals has emerged as an alternative long-term strategy for the control of tuberculosis (TB). A trial under field conditions was conducted in a TB-free goat herd to assess the safety of the Mycobacterium bovis BCG vaccine. Eleven kids and 10 milking goats were vaccinated with BCG. Bacterial shedding and interferon gamma (IFN-γ) responses were monitored throughout the study. Comprehensive pathological examination and mycobacterial culture of target tissues were performed. BCG vaccine strain was only isolated from the draining lymph node of the injection site of a kid euthanized at week 8 post-vaccination. The remaining animals were euthanized at week 24. Six out of 20 showed small granulomas at the injection site. BCG shedding was not detected in either faeces or in milk throughout the study. All vaccinated kids showed BCG-induced IFN-γ responses at week 8 post-vaccination. BCG vaccination of goats showed no lack of biological safety for the animals, environment and public health, and local adverse reactions were negligible. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Procedure for the elaboration of extended sources beta and/or gamma emitting

    International Nuclear Information System (INIS)

    Tejera R, A.; Cortes P, A.; Becerril V, A.

    1991-12-01

    In the laboratory of radioactive standards they have been come manufacturing punctual sources gauged gamma emitting during several years. Before the demand of extended radioactive homogeneous sources of beta particles emitting, in particular with nuclides that are simultaneously gamma and beta emitting, it was designed a procedure for it elaboration based on the one that we use at the moment for the elaboration of the punctual gamma sources. This procedure consists on the integration of a compact group of this type of sources on a single extended support, sealed one of its faces with a film of transparent material in satisfactory grade to the beta particles. In this work this procedure is described and it is applied in the elaboration of two sources that its were requested by the Laguna Verde Central (CFE), one with area of 20 cm 2 and the other one of 100 cm 2 . The homogeneity, measure as the dispersion of the activities of the aliquot ones distributed in the active surfaces was inside 2%. The percentage of attenuation of the beta particles was also measured by the film (window) with the one that the sources were sealed. (Author)

  13. Beta, but not gamma, band oscillations index visual form-motion integration.

    Directory of Open Access Journals (Sweden)

    Charles Aissani

    Full Text Available Electrophysiological oscillations in different frequency bands co-occur with perceptual, motor and cognitive processes but their function and respective contributions to these processes need further investigations. Here, we recorded MEG signals and seek for percept related modulations of alpha, beta and gamma band activity during a perceptual form/motion integration task. Participants reported their bound or unbound perception of ambiguously moving displays that could either be seen as a whole square-like shape moving along a Lissajou's figure (bound percept or as pairs of bars oscillating independently along cardinal axes (unbound percept. We found that beta (15-25 Hz, but not gamma (55-85 Hz oscillations, index perceptual states at the individual and group level. The gamma band activity found in the occipital lobe, although significantly higher during visual stimulation than during base line, is similar in all perceptual states. Similarly, decreased alpha activity during visual stimulation is not different for the different percepts. Trial-by-trial classification of perceptual reports based on beta band oscillations was significant in most observers, further supporting the view that modulation of beta power reliably index perceptual integration of form/motion stimuli, even at the individual level.

  14. Distinct interferon-gamma and interleukin-9 expression in cutaneous and oral lichen planus.

    Science.gov (United States)

    Weber, B; Schlapbach, C; Stuck, M; Simon, H-U; Borradori, L; Beltraminelli, H; Simon, D

    2017-05-01

    Cutaneous (CLP) and oral lichen planus (OLP) as the main subtypes of lichen planus (LP) present with different clinical manifestation and disease course, although their histopathologic features such as the band-like lymphocyte infiltrate and keratinocyte apoptosis are similar. So far, the underlying cellular and molecular mechanisms remain poorly understood. The aim of this study was to characterize and compare the in situ cellular infiltrates, cytokine expression profiles and apoptosis markers in CLP and OLP. Using immunofluorescence staining and laser scanning microscopy, we evaluated the cellular infiltrate (CD1a, CD3, CD4, CD8, CD21, CD57, CD123), cytokine expression (interleukin (IL)-1, IL-6, IL-9, IL-10, IL-17, IL-22, IL-23, tumour necrosis factor-α, transforming growth factor-β, interferon (IFN)-γ), and apoptosis markers (Fas, Fas ligand, cleaved caspase-3, TUNEL) of 21 anonymized biopsy specimens of LP (11 CLP, 10 OLP). Among infiltrating cells mainly T cells and natural killer (NK) cells as well as plasmacytoid dendritic cells (DC) were observed. A predominance of CD8+ T cells was noted in OLP. In both CLP and OLP, T helper (Th)1, Th9, Th17, and Th22-type cytokines were expressed. The expression of IL-9, IFN-γ and IL-22 was higher in CLP compared to that of OLP (P = 0.0165; P = 0.0016; P = 0.052 respectively). Expression of Fas and Fas ligand as well as cleaved caspase-3-positive cells was observed in the epithelium of all LP samples. The cell and cytokine patterns of CLP and OLP were partially distinct and generally resembled those reported for autoimmune diseases. The presence of CD8+ and NK cells as well as Fas/Fas ligand expression suggested that various pathways involved in keratinocyte apoptosis are relevant for LP. These results might help to establish targeted therapies for LP. © 2016 European Academy of Dermatology and Venereology.

  15. Beta and gamma oscillatory activities associated with olfactory memory tasks: different rhythms for different functional networks?

    Science.gov (United States)

    Martin, Claire; Ravel, Nadine

    2014-01-01

    Olfactory processing in behaving animals, even at early stages, is inextricable from top down influences associated with odor perception. The anatomy of the olfactory network (olfactory bulb, piriform, and entorhinal cortices) and its unique direct access to the limbic system makes it particularly attractive to study how sensory processing could be modulated by learning and memory. Moreover, olfactory structures have been early reported to exhibit oscillatory population activities easy to capture through local field potential recordings. An attractive hypothesis is that neuronal oscillations would serve to "bind" distant structures to reach a unified and coherent perception. In relation to this hypothesis, we will assess the functional relevance of different types of oscillatory activity observed in the olfactory system of behaving animals. This review will focus primarily on two types of oscillatory activities: beta (15-40 Hz) and gamma (60-100 Hz). While gamma oscillations are dominant in the olfactory system in the absence of odorant, both beta and gamma rhythms have been reported to be modulated depending on the nature of the olfactory task. Studies from the authors of the present review and other groups brought evidence for a link between these oscillations and behavioral changes induced by olfactory learning. However, differences in studies led to divergent interpretations concerning the respective role of these oscillations in olfactory processing. Based on a critical reexamination of those data, we propose hypotheses on the functional involvement of beta and gamma oscillations for odor perception and memory.

  16. Beta and gamma oscillatory activities associated with olfactory memory tasks: Different rhythms for different functional networks?

    Directory of Open Access Journals (Sweden)

    Claire eMartin

    2014-06-01

    Full Text Available Olfactory processing in behaving animals, even at early stages, is inextricable from top down influences associated with odor perception. The anatomy of the olfactory network (olfactory bulb, piriform and entorhinal cortices and its unique direct access to the limbic system makes it particularly attractive to study how sensory processing could be modulated by learning and memory. Moreover, olfactory structures have been early reported to exhibit oscillatory population activities easy to capture through local field potential recordings. An attractive hypothesis is that neuronal oscillations would serve to ‘bind’ distant structures to reach a unified and coherent perception. In relation to this hypothesis, we will assess the functional relevance of different types of oscillatory activity observed in the olfactory system of behaving animals. This review will focus primarily on two types of oscillatory activities: beta (15-40 Hz and gamma (60-100 Hz. While gamma oscillations are dominant in the olfactory system in the absence of odorant, both beta and gamma rhythms have been reported to be modulated depending on the nature of the olfactory task. Studies from the authors of the present review and other groups brought evidence for a link between these oscillations and behavioral changes induced by olfactory learning. However, differences in studies led to divergent interpretations concerning the respective role of these oscillations in olfactory processing. Based on a critical reexamination of those data, we propose hypotheses on the functional involvement of beta and gamma oscillations for odor perception and memory.

  17. Effects of beta/gamma radiation on nuclear waste glasses

    International Nuclear Information System (INIS)

    Weber, W.J.

    1997-01-01

    A key challenge in the disposal of high-level nuclear waste (HLW) in glass waste forms is the development of models of long-term performance based on sound scientific understanding of relevant phenomena. Beta decay of fission products is one source of radiation that can impact the performance of HLW glasses through the interactions of the emitted β-particles and g-rays with the atoms in the glass by ionization processes. Fused silica, alkali silicate glasses, alkali borosilicate glasses, and nuclear waste glasses are all susceptible to radiation effects from ionization. In simple glasses, defects (e.g., non-bridging oxygen and interstitial molecular oxygen) are observed experimentally. In more complex glasses, including nuclear waste glasses, similar defects are expected, and changes in microstructure, such as the formation of bubbles, have been reported. The current state of knowledge regarding the effects of β/γ radiation on the properties and microstructure of nuclear waste glasses are reviewed. (author)

  18. A new, passive dosemeter for gamma, beta and neutron radiations

    Energy Technology Data Exchange (ETDEWEB)

    Jones, L A; Stokes, R P, E-mail: rpstokes@dstl.gov.uk [Defence Science and Technology Laboratory, Environmental Sciences Department, Alverstoke, Gosport, Hants, PO12 2DL (United Kingdom)

    2011-03-01

    The Defence Science and Technology Laboratory (Dstl) provides personal radiation dosimetry to the UK Ministry of Defence. Dstl has recently developed a dosemeter that is based on a combination of thermoluminescent and etched-track detectors. The Dstl Combined Dosemeter is capable of assessing doses due to photons, beta particles and neutrons. This paper presents the laboratory type testing results for the Combined Dosemeter, and also describes the procedure for calibrating the dosemeter for use in workplace neutron fields. The Combined Dosemeter meets the type test requirements that are relevant to its intended applications, and gives neutron doses that are within 50% of the true dose in the workplaces in which it is used, even when the wearer has the potential to be exposed to a variety of neutron spectra (e.g. on board nuclear-powered submarines).

  19. A new, passive dosemeter for gamma, beta and neutron radiations

    International Nuclear Information System (INIS)

    Jones, L A; Stokes, R P

    2011-01-01

    The Defence Science and Technology Laboratory (Dstl) provides personal radiation dosimetry to the UK Ministry of Defence. Dstl has recently developed a dosemeter that is based on a combination of thermoluminescent and etched-track detectors. The Dstl Combined Dosemeter is capable of assessing doses due to photons, beta particles and neutrons. This paper presents the laboratory type testing results for the Combined Dosemeter, and also describes the procedure for calibrating the dosemeter for use in workplace neutron fields. The Combined Dosemeter meets the type test requirements that are relevant to its intended applications, and gives neutron doses that are within 50% of the true dose in the workplaces in which it is used, even when the wearer has the potential to be exposed to a variety of neutron spectra (e.g. on board nuclear-powered submarines).

  20. New detection modules for gamma, beta and X-ray cameras

    International Nuclear Information System (INIS)

    Azman, S.; Bolle, E.; Dang, K.Q.; Dang, W.; Dietzel, K.I.; Froberg, T.; Gaarder, P.E.; Gjaerum, J.A.; Haugen, S.H.; Hellum, G.; Henriksen, J.R.; Johanson, T.M.; Kobbevik, A.; Maehlum, G.; Meier, D.; Mikkelsen, S.; Ninive, I.; Oya, P.; Pavlov, N.; Pettersen, D.M.; Sundal, B.M.; Talebi, J.; Yoshioka, K.

    2003-01-01

    Full text: Ideas ASA is developing new detection modules for gamma, beta and X-ray cameras. Recent developments focus on modules using various semi-conductor materials (CZT, HgI, Si). The development includes ASIC design, detector module development, and implementation in camera heads. In this presentation we describe the characteristics of important ASICs and its properties in terms of electronic noise, and the modes for measuring signals (switched current modes, sparsified modes, self triggered modes). The ASICs are specific for detectors and applications. We describe recent developments using various semi - conductor materials. We describe important design aspects for medical applications and in life science (SPECT, beta, X-ray cameras)

  1. Serial interferon-gamma release assays during treatment of active tuberculosis in young adults

    Directory of Open Access Journals (Sweden)

    Lee Choon-Taek

    2010-10-01

    Full Text Available Abstract Background The role of interferon-γ release assay (IGRA in monitoring responses to anti-tuberculosis (TB treatment is not clear. We evaluated the results of the QuantiFERON-TB Gold In-tube (QFT-GIT assay over time during the anti-TB treatment of adults with no underlying disease. Methods We enrolled soldiers who were newly diagnosed with active TB and admitted to the central referral military hospital in South Korea between May 1, 2008 and September 30, 2009. For each participant, we preformed QFT-GIT assay before treatment (baseline and at 1, 3, and 6 months after initiating anti-TB medication. Results Of 67 eligible patients, 59 (88.1% completed the study protocol. All participants were males who were human immunodeficiency virus (HIV-negative and had no chronic diseases. Their median age was 21 years (range, 20-48. Initially, 57 (96.6% patients had positive QFT-GIT results, and 53 (89.8%, 42 (71.2%, and 39 (66.1% had positive QFT-GIT results at 1, 3, and 6 months, respectively. The IFN-γ level at baseline was 5.31 ± 5.34 IU/ml, and the levels at 1, 3, and 6 months were 3.95 ± 4.30, 1.82 ± 2.14, and 1.50 ± 2.12 IU/ml, respectively. All patients had clinical and radiologic improvements after treatment and were cured. A lower IFN-γ level, C-reactive protein ≥ 3 mg/dl, and the presence of fever (≥ 38.3°C at diagnosis were associated with negative reversion of the QFT-GIT assay. Conclusion Although the IFN-γ level measured by QFT-GIT assay decreased after successful anti-TB treatment in most participants, less than half of them exhibited QFT-GIT reversion. Thus, the reversion to negativity of the QFT-GIT assay may not be a good surrogate for treatment response in otherwise healthy young patients with TB.

  2. NORdic trial of oral Methylprednisolone as add-on therapy to Interferon beta-1a for treatment of relapsing-remitting Multiple Sclerosis (NORMIMS study): a randomised, placebo-controlled trial

    DEFF Research Database (Denmark)

    Sorensen, Per Soelberg; Mellgren, Svein Ivar; Svenningsson, Anders

    2009-01-01

    BACKGROUND: Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly effective, and new more effective and safe strategies are needed. Our aim was to assess the efficacy of oral methylprednisolone as an add-on therapy to subcutaneous interferon beta-1a to reduce...... was 0.22 for methylprednisolone compared with 0.59 for placebo (62% reduction, 95% CI 39-77%; pSleep disturbance and neurological and psychiatric symptoms were the most frequent adverse events recorded in the methylprednisolone group. Bone mineral density had not changed after 96 weeks......, these findings need to be corroborated in larger cohorts....

  3. Rat beta-LPH, gamma-LPH and beta-endorphin biosynthesized by isolated cells of pars intermedia and pars distalis

    International Nuclear Information System (INIS)

    Gianoulakis, C.; Seidah, N.G.; Routhier, R.; Chretien, M.

    1980-01-01

    Rats pars intermedia cells were incubated for 3 h with the following amino-acids: a) 35 S-methionine and 3 H-phenylalamine; b) 3 H-valine; and c) 3 H-valine and 3 H-lysine. Radioactive gamma-lipotropin, beta-lipotropin and beta-endorphin were purified on carboxy- methyl-cellulose and characterized by polyacrylamide disc gel electrophoresis af pH 4.5, molecular weight estimation and microsequencing. Rat gamma-lipotropin was shown to differ slightly from ovine gamma-lipotropin in its NH 2 -terminal amino acid sequence, in containing no methionine and having phenylalanine at position 6, valine at positions 13 and 27, and lysine at position 20. The same variations were observed in the sequence of rat beta-lipotropin, while rat beta-endorphin was shown to be identical to the ovine beta-endorphin. Following a 3-h pulse of rat pars distalis, the cells were extracted with care to avoid beta-lipotropin degradation by proteolytic enzymes. A peptide was purified and identified to be rat beta-endorphin, thus demonstrating that beta-endorphin is biosynthesized in pars distalis and is not an extraction artifact. (author)

  4. Proceedings of the International Symposium Advances in alpha, Beta- and Gamma-Ray spectrometry

    International Nuclear Information System (INIS)

    1997-01-01

    The International Committee for Radionuclide Metrology (ICRM) is an association of radionuclide metrology laboratories whose membership is composed of delegates of these laboratories together with other scientists actively engaged in the study and applications of radioactivity. The scientific activities are carried out in the frame of six Working Groups. Two of them, the Alpha-Particle Spectrometry and the Gamma-and Beta-ray Spectrometry Working Groups held a common workshop in Pushkin, St. Petersburg, 18 to 20 September 1996, under the title Advances in Alpha-Beta-and Gamma-Ray Sepectrometry, at the kind invitation of the D.I. Mendeleyev Institute for Metrology. More than 30 people from 14 laboratories attended the meeting, and nineteen oral communications were presented, from which twelve were retained for publication an are included in these proceedings. (Author)

  5. Solute transport and the prediction of breakaway oxidation in gamma + beta Ni-Cr-Al alloys

    Science.gov (United States)

    Nesbitt, J. A.; Heckel, R. W.

    1984-01-01

    The Al transport and the condition leading to breakaway oxidation during the cyclic oxidation of gamma + beta NiCrAl alloys have been studied. The Al concentration/distance profiles were measured after various cyclic oxidation exposures at 1200 C. It was observed that cyclic oxidation results in a decreasing Al concentration at the oxide/metal interface, maintaining a constant flux of Al to the Al2O3 scale. It was also observed that breakaway oxidation occurs when the Al concentration at the oxide/metal interface approaches zero. A numerical model was developed to simulate the diffusional transport of Al and to predict breakaway oxidation in gamma + beta NiCrAl alloys undergoing cyclic oxidation. In a comparison of two alloys with similar oxide spalling characteristics, the numerical model was shown to predict correctly the onset of breakaway oxidation in the higher Al-content alloy.

  6. Scintillation characteristics of phosphich-detector for detection of beta- and gamma-radiations

    CERN Document Server

    Ananenko, A A; Gavrilyuk, V

    2002-01-01

    The results of the study on the influence of individual peculiarities of the compound scintillation detector structure on the value and stability of the light yield by the gamma- and beta-radiation combined registration are presented. The phosphich detector is manufactured from the sodium iodide monocrystal, activated by thallium, and the scintillation plastic on the polystyrol basis. The comparison of the experimental results with the mathematical modeling data revealed certain regularities of the process of forming the phosphich detector light signal. The recommendations are worked out by means whereof the following characteristics of the scintillation unit: the light yield and its stability, amplitude resolution and the peak-to-valley ratio by the gamma- and beta-radiation registration were improved

  7. An analytical model to calculate absorbed fractions for internal dosimetry with alpha, beta and gamma emitters

    OpenAIRE

    Amato, Ernesto; Italiano, Antonio; Baldari, Sergio

    2014-01-01

    We developed a general model for the calculation of absorbed fractions in ellipsoidal volumes of soft tissue uniformly filled with alpha, beta and gamma emitting radionuclides. The approach exploited Monte Carlo simulations with the Geant4 code to determine absorbed fractions in ellipsoids characterized by a wide range of dimensions and ellipticities, for monoenergetic emissions of each radiation type. The so-obtained absorbed fractions were put in an analytical relationship with the 'general...

  8. Patterns of alpha, beta and gamma diversity of the herpetofauna in Mexico’s Pacific lowlands and adjacent interior valleys

    Directory of Open Access Journals (Sweden)

    García, A.

    2007-12-01

    Full Text Available The latitudinal distribution patterns of alpha, beta and gamma diversity of reptiles, amphibians and herpetofauna were analyzed using individual binary models of potential distribution for 301 species predicted by ecological modelling for a grid of 9,932 quadrants of ~25 km2 each. We arranged quadrants in 312 latitudinal bands in which alpha, beta and gamma values were determined. Latitudinal trends of all scales of diversity were similar in all groups. Alpha and gamma responded inversely to latitude whereas beta showed a high latitudinal fluctuation due to the high number of endemic species. Alpha and gamma showed a strong correlation in all groups. Beta diversity is an important component of the herpetofauna distribution patterns as a continuous source of species diversity throughout the region.

  9. Responses of a grassland arthropod community to chronic beta and gamma radiation

    International Nuclear Information System (INIS)

    Styron, C.E.; Dodson, G.J.; Beauchamp, J.J.; Miller, F.L. Jr.

    1976-01-01

    A long-term project was initiated in 1968 at Oak Ridge National Laboratory to assess effects of mixed beta and gamma radiation from simulated fallout on a grassland ecosystem. Beta and gamma radiation dose rates in microhabitats of the experimentally contaminated enclosure were measured with LiF thermoluminescent microdosimeters. Extensive statistical analyses of data on numbers of individuals collected for each of 76 arthropod and 2 molluscan taxa have identified no lasting significant changes in similarity or species diversity of experimental versus control communities as the result of the long-term irradiation at low dose rates. Natural fluctuations in community dynamics obscured any possible radiation effects. Thus, the apparent threshold for mixed beta and gamma radiation inducing changes in community structure must be above the exposure rate range of 2.3 to 13 rad/day delivered during the 5 yr of observation. Establishing such a threshold is of importance in assessing the impact of communities subjected to chronic, low level environmental exposure to ionizing radiation

  10. Gamma and Beta Oscillations in Human MEG Encode the Contents of Vibrotactile Working Memory

    Directory of Open Access Journals (Sweden)

    Alexander H. von Lautz

    2017-12-01

    Full Text Available Ample evidence suggests that oscillations in the beta band represent quantitative information about somatosensory features during stimulus retention. Visual and auditory working memory (WM research, on the other hand, has indicated a predominant role of gamma oscillations for active WM processing. Here we reconciled these findings by recording whole-head magnetoencephalography during a vibrotactile frequency comparison task. A Braille stimulator presented healthy subjects with a vibration to the left fingertip that was retained in WM for comparison with a second stimulus presented after a short delay. During this retention interval spectral power in the beta band from the right intraparietal sulcus and inferior frontal gyrus (IFG monotonically increased with the to-be-remembered vibrotactile frequency. In contrast, induced gamma power showed the inverse of this pattern and decreased with higher stimulus frequency in the right IFG. Together, these results expand the previously established role of beta oscillations for somatosensory WM to the gamma band and give further evidence that quantitative information may be processed in a fronto-parietal network.

  11. Monte Carlo simulation of {beta}-{gamma} coincidence system using plastic scintillators in 4{pi} geometry

    Energy Technology Data Exchange (ETDEWEB)

    Dias, M.S. [Instituto de Pesquisas Energeticas e Nucleares: IPEN-CNEN/SP, Av. Prof. Lineu Prestes 2242, 05508-000 Sao Paulo, SP (Brazil)], E-mail: msdias@ipen.br; Piuvezam-Filho, H. [Instituto de Pesquisas Energeticas e Nucleares: IPEN-CNEN/SP, Av. Prof. Lineu Prestes 2242, 05508-000 Sao Paulo, SP (Brazil); Baccarelli, A.M. [Departamento de Fisica-PUC/SP-Rua Marques de Paranagua 111, 01303-050 Sao Paulo, SP (Brazil); Takeda, M.N. [Universidade Santo Amaro, UNISA-Rua Prof. Eneas da Siqueira Neto 340, 04829-300 Sao Paulo, SP (Brazil); Koskinas, M.F. [Instituto de Pesquisas Energeticas e Nucleares: IPEN-CNEN/SP, Av. Prof. Lineu Prestes 2242, 05508-000 Sao Paulo, SP (Brazil)

    2007-09-21

    A modified version of a Monte Carlo code called Esquema, developed at the Nuclear Metrology Laboratory in IPEN, Sao Paulo, Brazil, has been applied for simulating a 4{pi}{beta}(PS)-{gamma} coincidence system designed for primary radionuclide standardisation. This system consists of a plastic scintillator in 4{pi} geometry, for alpha or electron detection, coupled to a NaI(Tl) counter for gamma-ray detection. The response curves for monoenergetic electrons and photons have been calculated previously by Penelope code and applied as input data to code Esquema. The latter code simulates all the disintegration processes, from the precursor nucleus to the ground state of the daughter radionuclide. As a result, the curve between the observed disintegration rate as a function of the beta efficiency parameter can be simulated. A least-squares fit between the experimental activity values and the Monte Carlo calculation provided the actual radioactive source activity, without need of conventional extrapolation procedures. Application of this methodology to {sup 60}Co and {sup 133}Ba radioactive sources is presented and showed results in good agreement with a conventional proportional counter 4{pi}{beta}(PC)-{gamma} coincidence system.

  12. Screening procedures for alpha, beta and gamma emitting radionuclides in urine

    International Nuclear Information System (INIS)

    Kramer, G.H.; Gardner, S.E.; Johnson, J.R.

    1983-08-01

    The gross actinide and beta screening methods currently used by the Bioassay Laboratory at Chalk River Nuclear Laboratories have been documented and tested. The gross gamma method has also been documented. The gross actinide method was tested with Th-nat, Pu-239, Np-237, Am-241 and Cm-244 and the average percent recoveries were 90, 99, 45, 72 and 78, respectively. The gross beta method was tested with Sr-90/Y-90, Ce-144/Pr-144, Pm-147 and Ba-133 and the average percent recoveries were 78, 100, 46 and 46, respectively. Detection limits for the gross actinide (alpha) method are found to be about 0.4 mBq and about 39 mBq for the gross beta method

  13. Use of a recombinant vaccinia virus expressing interferon gamma for post-exposure protection against vaccinia and ectromelia viruses.

    Directory of Open Access Journals (Sweden)

    Susan A Holechek

    Full Text Available Post-exposure vaccination with vaccinia virus (VACV has been suggested to be effective in minimizing death if administered within four days of smallpox exposure. While there is anecdotal evidence for efficacy of post-exposure vaccination this has not been definitively studied in humans. In this study, we analyzed post-exposure prophylaxis using several attenuated recombinant VACV in a mouse model. A recombinant VACV expressing murine interferon gamma (IFN-γ was most effective for post-exposure protection of mice infected with VACV and ectromelia virus (ECTV. Untreated animals infected with VACV exhibited severe weight loss and morbidity leading to 100% mortality by 8 to 10 days post-infection. Animals treated one day post-infection had milder symptoms, decreased weight loss and morbidity, and 100% survival. Treatment on days 2 or 3 post-infection resulted in 40% and 20% survival, respectively. Similar results were seen in ECTV-infected mice. Despite the differences in survival rates in the VACV model, the viral load was similar in both treated and untreated mice while treated mice displayed a high level of IFN-γ in the serum. These results suggest that protection provided by IFN-γ expressed by VACV may be mediated by its immunoregulatory activities rather than its antiviral effects. These results highlight the importance of IFN-γ as a modulator of the immune response for post-exposure prophylaxis and could be used potentially as another post-exposure prophylaxis tool to prevent morbidity following infection with smallpox and other orthopoxviruses.

  14. Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium.

    Science.gov (United States)

    Abe, Ayumi; Takano, Kenichi; Kojima, Takashi; Nomura, Kazuaki; Kakuki, Takuya; Kaneko, Yakuto; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo

    2016-06-01

    Tight junctions (TJs) are necessary for salivary gland function and may serve as indicators of salivary gland epithelial dysfunction. IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition which disrupts the TJ associated epithelial barrier. The salivary glands are one of the most frequently involved organs in IgG4-RD, however, changes of the TJ associated epithelial barrier in salivary gland duct epithelium is poorly understood. Here, we investigated the regulation and function of TJs in human submandibular gland ductal epithelial cells (HSDECs) in normal and IgG4-RD. We examined submandibular gland (SMG) tissue from eight control individuals and 22 patients with IgG4-RD and established an HSDEC culture system. Immunohistochemistry, immunocytochemistry, western blotting, and measurement of transepithelial electrical resistance (TER) were performed. Claudin-4, claudin-7, occludin, and JAM-A were expressed at the apical side of the duct epithelium in submandibular gland (SMG) tissue and at the cell borders in HSDECs of normal and IgG4-RD. The expression and distribution of TJs in SMG tissue were not different in control individuals and patients with IgG4-RD in vivo and in vitro. Although interferon-gamma (IFNγ) generally disrupts the integrity and function of TJs, as manifested by decreased epithelial barrier function, IFNγ markedly increased the epithelial barrier function of HSDECs via upregulation of claudin-7 expression in HSDECs from patients with IgG4-RD. This is the first report showing an IFNγ-dependent increase in epithelial barrier function in the salivary gland duct epithelium. Our results provide insights into the functional significance of TJs in salivary gland duct epithelium in physiological and pathological conditions, including IgG4-RD.

  15. Secretion of Interferon gamma (IFNγ) from Human Immune Cells is Altered by Exposure to Tributyltin (TBT) and Dibutyltin (DBT)

    Science.gov (United States)

    Lawrence, Shanieek; Reid, Jacqueline; Whalen, Margaret

    2013-01-01

    Tributyltin (TBT) and dibutyltin (DBT) are widespread environmental contaminants found in food, beverages, and human blood samples. Both of these butyltins (BTs) interfere with the ability of human natural killer (NK) cells to lyse target cells and also alter secretion of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) from human immune cells in vitro. The capacity of BTs to interfere with secretion of other pro-inflammatory cytokines has not been examined. Interferon gamma (IFNγ) is a modulator of adaptive and innate immune responses, playing an important role in overall immune competence. This study shows that both TBT and DBT alter secretion of IFNγ from human immune cells. Peripheral blood cell preparations that were increasingly reconstituted were used to determine if exposures to either TBT or DBT affected IFNγ secretion and how the makeup of the cell preparation influenced that effect. IFNγ secretion was examined after 24 h, 48 h and 6 day exposures to TBT (200- 2.5 nM) and DBT (5- 0.05 μM) in highly enriched human NK cells, a monocyte-depleted preparation of PBMCs, and monocyte-containing PBMCs. Both BTs altered IFNγ secretion from NK cells at most of the conditions tested (either increasing or decreasing secretion). However, there was significant variability among donors as to the concentrations and time points that showed changes as well as the baseline secretion of IFNγ. The majority of donors showed an increase in IFNγ secretion in response to at least one concentration of TBT or DBT at a minimum of one length of exposure. PMID:24357260

  16. Diagnosis of Coxiella burnetii infection: comparison of a whole blood interferon-gamma production assay and a Coxiella ELISPOT.

    Directory of Open Access Journals (Sweden)

    Teske Schoffelen

    Full Text Available Diagnosis of ongoing or past infection with Coxiella burnetii, the causative agent of Q fever, relies heavily on serology: the measurement of C. burnetii-specific antibodies, reflecting the host's humoral immune response. However, cell-mediated immune responses play an important, probably even more relevant, role in infections caused by the intracellular C. burnetii bacterium. Recent studies have investigated interferon-gamma (IFN-γ based assays, including a whole-blood IFN-γ production assay and a Coxiella enzyme-linked immunospot (Coxiella ELISPOT, as potential diagnostic tools for Q fever diagnosis. Both are in-house developed assays using stimulating antigens of different origin. The main objective of this study was to compare the test performance of the IFN-γ production assay and the Coxiella ELISPOT for detecting a cellular immune response to C. burnetii in Q fever patients, and to assess the correlation between both assays. To that end, both tests were performed in a well-defined patient group of chronic Q fever patients (n = 16 and a group of healthy seronegative individuals (n = 17. Among patients, both the Coxiella ELISPOT and the IFN-γ production assay detected positive response in 14/16. Among controls, none were positive in the Coxiella ELISPOT, whereas the IFN-γ production assay detected positive results in 1/17 and 3/17, when using Henzerling and Nine Mile as stimulating antigens, respectively. These results suggest the Coxiella ELISPOT has a somewhat higher specificity than the IFN-γ production assay when Nine Mile is used as antigen stimulus. The assays showed moderate correlation: the Spearman correlation coefficient r ranged between 0.37-0.60, depending on the antigens used. Further investigation of the diagnostic potential for C. burnetii infection of both assays is warranted.

  17. Period concatenation underlies interactions between gamma and beta rhythms in neocortex

    Directory of Open Access Journals (Sweden)

    Anita K Roopun

    2008-04-01

    Full Text Available The neocortex generates rhythmic electrical activity over a frequency range covering many decades. Specific cognitive and motor states are associated with oscillations in discrete frequency bands within this range, but it is not known whether interactions and transitions between distinct frequencies are of functional importance. When coexpressed rhythms have frequencies that differ by a factor of two or more interactions can be seen in terms of phase synchronization. Larger frequency differences can result in interactions in the form of nesting of faster frequencies within slower ones by a process of amplitude modulation. It is not known how coexpressed rhythms, whose frequencies differ by less than a factor of two may interact. Here we show that two frequencies (gamma – 40 Hz and beta2 – 25 Hz, coexpressed in superficial and deep cortical laminae with low temporal interaction, can combine to generate a third frequency (beta1 – 15 Hz showing strong temporal interaction. The process occurs via period concatenation, with basic rhythm-generating microcircuits underlying gamma and beta2 rhythms forming the building blocks of the beta1 rhythm by a process of addition. The mean ratio of adjacent frequency components was a constant – approximately the golden mean – which served to both minimize temporal interactions, and permit multiple transitions, between frequencies. The resulting temporal landscape may provide a framework for multiplexing – parallel information processing on multiple temporal scales.

  18. Response-surface models for deterministic effects of localized irradiation of the skin by discrete {beta}/{gamma} -emitting sources

    Energy Technology Data Exchange (ETDEWEB)

    Scott, B.R.

    1995-12-01

    Individuals who work at nuclear reactor facilities can be at risk for deterministic effects in the skin from exposure to discrete {Beta}- and {gamma}-emitting ({Beta}{gamma}E) sources (e.g., {Beta}{gamma}E hot particles) on the skin or clothing. Deterministic effects are non-cancer effects that have a threshold and increase in severity as dose increases (e.g., ulcer in skin). Hot {Beta}{gamma}E particles are {sup 60}Co- or nuclear fuel-derived particles with diameters > 10 {mu}m and < 3 mm and contain at least 3.7 kBq (0.1 {mu}Ci) of radioactivity. For such {Beta}{gamma}E sources on the skin, it is the beta component of the dose that is most important. To develop exposure limitation systems that adequately control exposure of workers to discrete {Beta}{gamma}E sources, models are needed for systems that adequately control exposure of workers to discrete {Beta}{gamma}E sources, models are needed for evaluating the risk of deterministic effects of localized {Beta} irradiation of the skin. The purpose of this study was to develop dose-rate and irradiated-area dependent, response-surface models for evaluating risks of significant deterministic effects of localized irradiation of the skin by discrete {Beta}{gamma}E sources and to use modeling results to recommend approaches to limiting occupational exposure to such sources. The significance of the research results as follows: (1) response-surface models are now available for evaluating the risk of specific deterministic effects of localized irradiation of the skin; (2) modeling results have been used to recommend approaches to limiting occupational exposure of workers to {Beta} radiation from {Beta}{gamma}E sources on the skin or on clothing; and (3) the generic irradiated-volume, weighting-factor approach to limiting exposure can be applied to other organs including the eye, the ear, and organs of the respiratory or gastrointestinal tract and can be used for both deterministic and stochastic effects.

  19. $\\beta$3$p$-spectroscopy and proton-$\\gamma$ width determination in the decay of $^{31}$Ar

    CERN Multimedia

    We propose to perform a detailed study of the $\\beta$-decay of the dripline nucleus $^{31}$Ar. This will allow a detailed study of the $\\beta$-delayed 3$p$-decay as well as provide important information on the resonances of $^{30}$S and $^{29}$P, in particular the ratio between the $p$- and $\\gamma$- partial widths relevant for astrophysics.

  20. Human umbilical cord-derived mesenchymal stem cells utilise Activin-A to suppress Interferon-gamma production by natural killer cells.

    Directory of Open Access Journals (Sweden)

    Debanjana eChaterjee

    2014-12-01

    Full Text Available Following allogeneic hematopoietic stem cell transplantation (HSCT, interferon (IFN-gamma levels in the recipient’s body can strongly influence the clinical outcome. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs are lucrative as biological tolerance-inducers in HSCT settings. Hence, we studied the molecular mechanism of how UC-MSCs influence natural killer (NK cell-mediated IFN-gamma production. Allogeneic NK cells were cultured in direct contact with UC-MSCs or cell free supernatants from MSC cultures (MSC conditioned media. We found that soluble factors secreted by UC-MSCs strongly suppressed IL-12/IL-18-induced IFN-gamma production by NK cells by reducing phosphorylation of STAT4, NF-kB as well as T-bet activity. UC-MSCs secreted considerable amounts of Activin-A, which could suppress IFN-gamma production by NK cells. Neutralisation of Activin-A in MSC-conditioned media significantly abrogated their suppressive abilities. Till date, multiple groups have reported that prostaglandin (PG-E2 produced by MSCs can suppress NK cell functions. Indeed, we found that inhibition of PGE2 production by MSCs could also significantly restore IFN-gamma production. However, the effects of Activin-A and PGE2 were not cumulative. To the best of our knowledge, we are first to report the role of Activin-A in MSC-mediated suppression of IFN-gamma production by NK cells.

  1. Cytokines interleukin-1beta and tumor necrosis factor-alpha regulate different transcriptional and alternative splicing networks in primary beta-cells

    DEFF Research Database (Denmark)

    Ortis, Fernanda; Naamane, Najib; Flamez, Daisy

    2010-01-01

    by the cytokines interleukin (IL)-1beta + interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha + IFN-gamma in primary rat beta-cells. RESEARCH DESIGN AND METHODS: Fluorescence-activated cell sorter-purified rat beta-cells were exposed to IL-1beta + IFN-gamma or TNF-alpha + IFN-gamma for 6 or 24 h......-cells, with temporal differences in the number of genes modulated by IL-1beta + IFNgamma or TNF-alpha + IFN-gamma. These cytokine combinations induced differential expression of inflammatory response genes, which is related to differential induction of IFN regulatory factor-7. Both treatments decreased the expression...... of genes involved in the maintenance of beta-cell phenotype and growth/regeneration. Cytokines induced hypoxia-inducible factor-alpha, which in this context has a proapoptotic role. Cytokines also modified the expression of >20 genes involved in RNA splicing, and exon array analysis showed cytokine...

  2. Beta-glucan ameliorates gamma-rays induced oxidative injury in male Swiss albino rats

    International Nuclear Information System (INIS)

    Salama, S.F.

    2011-01-01

    1,3-beta-D-Glucan is a natural polysaccharide derived from the cell walls of bakers yeast Saccharomyces cerevsiae with immunoenhancing and potent antioxidant effects. This study investigated the pathways through which beta-glucan gavage treatment (50mg/kg) exerts its effect on radiation-induced oxidative damage in male rats. Beta-glucan was given orally to male rats; 3 hours post gamma-irradiation at dose 5Gy, for 10 and 20 days post-irradiation level were assayed, being remarkable indicators in cell oxidative stress. Results pointed out that irradiation at 5Gy significantly depressed all blood parameters, such as erythrocytes count (RBCs), hemoglobin content (Hb), hematocrit value (Hct), total leucocytes count and absolute lymphocytes and neutrophils counts, blood glutathione (GSH) level and conversely elevated level of serum ascorbyl radical (AsR), product of lipid peroxidation (MDA melanodialdehyde), triglycerides and cholesterol. Total leucocytes count and absolute lymphocytes and neutrophils counts, RBCs, Hb, Hct, blood GSH and serum MDA of irradiated animals receiving beta-glucan administration were exhibited significant differences compared to the irradiated group. Marrow count and the percentage of viability and spleenocytes viability were also significantly decreased. Beta-glucan treatment accelerates recovery of cell damage induced by ionizing irradiation through its potential immune-enhancing activity and free radical scavenging ability that is partially mediated through stimulation of immunohaematological system thus could play a role in regulating irradiation complications

  3. Interactions Between the Canonical WNT/Beta-Catenin Pathway and PPAR Gamma on Neuroinflammation, Demyelination, and Remyelination in Multiple Sclerosis.

    Science.gov (United States)

    Vallée, Alexandre; Vallée, Jean-Noël; Guillevin, Rémy; Lecarpentier, Yves

    2018-05-01

    Multiple sclerosis (MS) is marked by neuroinflammation and demyelination with loss of oligodendrocytes in the central nervous system. The immune response is regulated by WNT/beta-catenin pathway in MS. Activated NF-kappaB, a major effector of neuroinflammation, and upregulated canonical WNT/beta-catenin pathway positively regulate each other. Demyelinating events present an upregulation of WNT/beta-catenin pathway, whereas proper myelinating phases show a downregulation of WNT/beta-catenin pathway essential for the promotion of oligodendrocytes precursors cells proliferation and differentiation. The activation of WNT/beta-catenin pathway results in differentiation failure and impairment in remyelination. However, PI3K/Akt pathway and TCF7L2, two downstream targets of WNT/beta-catenin pathway, are upregulated and promote proper remyelination. The interactions of these signaling pathways remain unclear. PPAR gamma activation can inhibit NF-kappaB, and can also downregulate the WNT/beta-catenin pathway. PPAR gamma and canonical WNT/beta-catenin pathway act in an opposite manner. PPAR gamma agonists appear as a promising treatment for the inhibition of demyelination and the promotion of proper remyelination through the control of both NF-kappaB activity and canonical WNT/beta-catenin pathway.

  4. Use of interferon-gamma release assays in a health care worker screening program: experience from a tertiary care centre in the United States.

    Science.gov (United States)

    Joshi, Manish; Monson, Thomas P; Woods, Gail L

    2012-01-01

    Interferon-gamma release assays including the QuantiFERON-TB Gold In-Tube test (QFT-GIT [Cellestis Ltd, Australia]) may be used in place of the tuberculin skin test (TST) in surveillance programs for Mycobacterium tuberculosis infection control. However, data on performance and practicality of the QFT-GIT in such programs for health care workers (HCWs) are limited. To assess the performance, practicality and reversion rate of the QFT-GIT among HCWs at a tertiary health care institution in the United States. Retrospective chart review of HCWs at Central Arkansas Veterans Healthcare System (Arkansas, USA) who underwent QFT-GIT testing as a part of their employee screening between November 1, 2008 and October 31, 2009. QFT-GIT was used to screen 3290 HCWs. The initial QFT-GIT was interpreted as positive for 129 (3.9%) HCWs, negative for 3155 (95.9%) and indeterminate for six (0.2%). Testing with QFT-GIT was repeated in 45 HCWs who had positive results on the initial test. The QFT-GIT reverted to negative in 18 (40.0%) HCWs, all of whom had negative TST status and initial interferon-gamma values of 0.35 IU⁄mL to 2.0 IU⁄mL. The QFT-GIT test is feasible in large health care setting as an alternative to TST for M tuberculosis infection screening in HCWs but is not free from challenges. The major concerns are the high number of positive test results and high reversion rates on repeat testing, illustrating poor short-term reproducibility of positive QFT-GIT test results. These results suggest adopting a borderline zone between interferon-gamma values of 0.35 IU⁄mL to 2.0 IU⁄mL, and cautious clinical interpretation of values in this range.

  5. Epithelial cells prime the immune response to an array of gut-derived commensals towards a tolerogenic phenotype through distinct actions of thymic stromal lymphopoietin and transforming growth factor-beta

    DEFF Research Database (Denmark)

    Zeuthen, Louise Hjerrild; Fink, Lisbeth Nielsen; Frøkiær, Hanne

    2007-01-01

    in DC priming of naive T cells with elevated levels of transforming growth factor-beta (TGF-beta) and markedly reduced levels of bacteria-induced interferon-gamma production. Caco2 cell production of IL-8, thymic stromal lymphopoietin (TSLP) and TGF-beta increases upon microbial stimulation in a strain...

  6. Clinical trial: a multicentre, randomized, double-blind, placebo-controlled, dose-finding, phase II study of subcutaneous interferon-beta-1a in moderately active ulcerative colitis

    DEFF Research Database (Denmark)

    Pena-Rossi, C; Schreiber, S; Golubovic, G

    2008-01-01

    Background Ulcerative colitis (UC) pathophysiology is characterized by an imbalance between pro- and anti-inflammatory cytokines. Interferon (IFN)-beta-1a has potent immunoregulatory properties, including stimulation of host defence mechanisms, and thus represents a potential treatment. Aim To ex...

  7. Interferon gamma release assays for the diagnosis of latent TB infection in HIV-infected individuals in a low TB burden country.

    LENUS (Irish Health Repository)

    Cheallaigh, Clíona Ní

    2013-01-01

    Interferon gamma release assays (IGRAs) are used to diagnose latent tuberculosis infection. Two IGRAs are commercially available: the Quantiferon TB Gold In Tube (QFT-IT) and the T-SPOT.TB. There is debate as to which test to use in HIV+ individuals. Previous publications from high TB burden countries have raised concerns that the sensitivity of the QFT-IT assay, but not the T-SPOT.TB, may be impaired in HIV+ individuals with low CD4+ T-cell counts. We sought to compare the tests in a low TB burden setting.

  8. The impact of HIV infection and CD4 cell count on the performance of an interferon gamma release assay in patients with pulmonary tuberculosis

    DEFF Research Database (Denmark)

    Aabye, Martine G.; Ravn, Pernille; PrayGod, George

    2009-01-01

    pulmonary tuberculosis (PTB) in a TB- and HIV-endemic population and the effect of HIV-infection and CD4 cell count on test performance. METHODOLOGY/PRINCIPAL FINDINGS: 161 patients with sputum culture confirmed PTB were subjected to HIV- and QFT-IT testing and measurement of CD4 cell count. The QFT......BACKGROUND: The performance of the tuberculosis specific Interferon Gamma Release Assays (IGRAs) has not been sufficiently documented in tuberculosis- and HIV-endemic settings. This study evaluated the sensitivity of the QuantiFERON TB-Gold In-Tube (QFT-IT) in patients with culture confirmed...

  9. Development and validation of cell-based luciferase reporter gene assays for measuring neutralizing anti-drug antibodies against interferon beta

    DEFF Research Database (Denmark)

    Hermanrud, Christina; Ryner, Malin; Luft, Thomas

    2016-01-01

    a normal distribution for the majority of runs, allowing a parametric approach for cut-point calculation to be used, where NAb positive samples could be identified with 95% confidence. An analysis of means and variances indicated that a floating cut-point should be used for all assays. The assays......Neutralizing anti-drug antibodies (NAbs) against therapeutic interferon beta (IFNβ) in people with multiple sclerosis (MS) are measured with cell-based bioassays. The aim of this study was to redevelop and validate two luciferase reporter-gene bioassays, LUC and iLite, using a cut-point approach...... to identify NAb positive samples. Such an approach is favored by the pharmaceutical industry and governmental regulatory agencies as it has a clear statistical basis and overcomes the limitations of the current assays based on the Kawade principle. The work was conducted following the latest assay guidelines...

  10. Development and Validation of an Enzyme-Linked Immunosorbent Assay for the Detection of Binding Anti-Drug Antibodies against Interferon Beta

    DEFF Research Database (Denmark)

    Ingenhoven, Kathleen; Kramer, Daniel; Jensen, Poul Erik Hyldgaard

    2017-01-01

    to be 26 ng/mL using commercially available polyclonal rabbit antihuman IFN-β in human sera as the positive control. CONCLUSION: An ultrasensitive ELISA for IFN-β-binding ADA testing has been validated. This will form the basis to assess anti-biopharmaceutical immunization toward IFN-β with regards to its......OBJECTIVE: To develop and validate a method for the detection of binding anti-drug antibodies (ADAs) against interferon beta (IFN-β) in human serum as part of a European initiative (ABIRISK) aimed at the prediction and analysis of clinical relevance of anti-biopharmaceutical immunization...... to minimize the risk. METHOD: A two-tiered bridging enzyme-linked immunosorbent assay (ELISA) format was selected and validated according to current recommendations. Screening assay: ADA in serum samples form complexes with immobilized IFN-β and biotinylated IFN-β, which are then detected using HRP labeled...

  11. Maternal and cord plasma concentrations of beta-lipotrophin, beta-endorphin and gamma-lipotrophin at delivery; effect of analgesia.

    Science.gov (United States)

    Browning, A J; Butt, W R; Lynch, S S; Shakespear, R A; Crawford, J S

    1983-12-01

    Maternal venous plasma concentrations of beta-LPH, beta-EP and gamma-LPH were compared in (i) patients undergoing vaginal delivery, 11 with an epidural block and 13 with pethidine and nitrous oxide or no analgesics; (ii) patients delivered by caesarean section, 7 under epidural block and 8 under general anaesthesia. Patients delivered by either method under epidural block had significantly lower levels of all three peptides than those receiving no epidural. There were significant negative correlations between umbilical vein beta-LPH, beta-EP and gamma-LPH concentrations and umbilical artery pH and positive correlations between beta-LPH and beta-EP but not gamma-LPH and cord PCO2 in 29 patients. There was no relation between cord levels of any of the three peptides and the method of analgesia or the route of delivery. Although concentrations of all three peptides were closely correlated to one another in either maternal or cord plasma, there was no relationship between maternal and fetal levels.

  12. A short 2 week dose titration regimen reduces the severity of flu-like symptoms with initial interferon gamma-1b treatment.

    Science.gov (United States)

    Devane, John G; Martin, Mary L; Matson, Mark A

    2014-06-01

    Flu-like symptoms (FLS) are commonly experienced by patients receiving interferon gamma-1b which may cause discontinuation or disruption of dosing during initial therapy or on re-initiation following a break in therapy. In contrast to Type I interferons, the impact of dose-titration on FLS has not been reported and is not a practice described or included in the approved prescribing information for interferon gamma-1b.The objective of this study was to assess the effect of a 2 week titration regimen on the severity of FLS during the initial 3 weeks of therapy with three times weekly subcutaneous injections of interferon gamma-1b. Healthy men and women were randomized into a double-blind, two-period, crossover study. Each study period was 3 weeks in duration and there was a minimum 15 day washout between treatment periods. Two treatment regimens were compared: No Titration dosing (full 50 mcg/m(2) subcutaneously [s.c.] three times weekly for 3 weeks) and Titration (15 mcg/m(2) s.c. three times weekly during week 1, 30 mcg/m(2) s.c. three times weekly during week 2 followed by the full dose of 50 mcg/m(2) s.c. three times weekly during week 3). Subjects remained in the clinic for at least 12 hours following each injection. FLS was based on a composite score for fever, chills, tiredness and muscle aches assessed at baseline and 4, 8 and 12 hours following each injection. Acetaminophen was allowed at the discretion of the PI. The primary endpoint was the change from baseline in FLS severity at 8 hours averaged over the 3 weeks of treatment. Additional endpoints included FLS at 4 and 12 hours, individual flu-like symptoms, rates of discontinuation, incidence of FLS and acetaminophen use. NCT 01929382. Of the 40 subjects randomized, there were 15 (37.5%) discontinuations. Titration resulted in a significant reduction in FLS severity at 8 hours (p = 0.023) averaged over the 3 week treatment period. The difference in 3 week FLS severity reflects differences

  13. An analytical model to calculate absorbed fractions for internal dosimetry with alpha, beta and gamma emitters

    Directory of Open Access Journals (Sweden)

    Ernesto Amato

    2014-03-01

    Full Text Available We developed a general model for the calculation of absorbed fractions in ellipsoidal volumes of soft tissue uniformly filled with alpha, beta and gamma emitting radionuclides. The approach exploited Monte Carlo simulations with the Geant4 code to determine absorbed fractions in ellipsoids characterized by a wide range of dimensions and ellipticities, for monoenergetic emissions of each radiation type. The so-obtained absorbed fractions were put in an analytical relationship with the 'generalized radius', calculated as 3V/S, where V is the ellipsoid volume and S its surface. Radiation-specific parametric functions were obtained in order to calculate the absorbed fraction of a given radiation in a generic ellipsoidal volume. The dose from a generic radionuclide can be calculated through a process of summation and integration over the whole radionuclide emission spectrum, profitably implemented in an electronic spreadsheet. We compared the results of our analytical calculation approach with those obtained from the OLINDA/EXM computer software, finding a good agreement in a wide range of sphere radii, for the high-energy pure beta emitter 90Y, the commonly employed beta-gamma emitter 131I, and the pure alpha emitter 213Po. The generality of our approach makes it useful an easy to implement in clinical dosimetry calculations as well as in radiation safety estimations when doses from internal radionuclide uptake are to be taken into account.

  14. Beta-gamma spectroscopy for double beta decays and Lepton number conservation

    International Nuclear Information System (INIS)

    Ejiri, H.; Takahashi, N.; Shibata, T.; Nagai, Y.; Okada, K.; Kamikubota, N.; Watanabe, T.

    1984-01-01

    In this paper neutrino-less double β decays (Oν ββ) of /sup 76/Ge were studied by means of the newly developed ELEGANTS (Electron gamma-ray neutrino spectrometer). It consists of a 171 cc pure Ge detector surrounded bu a big 4π-NaI detector, and active and inactive filters. Measurement of both the electron signal from the Ge detector and γ-ray signals from the 4π-NaI detector made it possible to select the true double decay events from background events due to the other radio-active isotopes and cosmic rays. The ELEGANTS showed the highest sensitivity for detecting the neutrino-less double β decay. The preliminary data obtained so far give a lower limit of the half life T/sub 1/2/≥2.2 10/sup 22/y for the O/sup +/→O/sup +/ Oν ββ decay and T/sub 1/2/ ≥1.5.10/sup 22/y for the O/sup +/→2/sup +/ Oν ββ decay of /sup 76/Ge

  15. TL glow curve analysis of UV, beta and gamma induced limestone collected from Amarnath holy cave

    Directory of Open Access Journals (Sweden)

    Vikas Dubey

    2015-01-01

    Full Text Available The paper reports themoluminescence glow curve analysis of UV (ultraviolet, β (beta and γ (gamma induced limestone collected from Amarnath holy cave. The collected natural sample was characterized by X-ray diffraction (XRD technique and crystallite size calculated by Scherer's formula. Surface morphology and particle size was calculated by transmission electron microscopy (TEM study. Effect of annealing temperature on collected lime stone examined by TL glow curve study. The limestone was irradiated by UV radiation (254 nm source and the TL glow curve recorded for different UV exposure time. For beta irradiation Sr90 source was used and is shows intense peak at 256 °C with a shoulder peak at higher temperature range. For gamma radiation Co60 source and TL glow curve recorded for different doses of gamma. The kinetic parameters calculation was performed for different glow curve by computerized glow curve deconvolution (CGCD technique. The chemical composition of natural limestone was analyzed by energy dispersive X-ray spectroscopy (EDXS.

  16. Hard beta and gamma emissions of 124I. Impact on occupational dose in PET/CT.

    Science.gov (United States)

    Kemerink, G J; Franssen, R; Visser, M G W; Urbach, C J A; Halders, S G E A; Frantzen, M J; Brans, B; Teule, G J J; Mottaghy, F M

    2011-01-01

    The hard beta and gamma radiation of 124I can cause high doses to PET/CT workers. In this study we tried to quantify this occupational exposure and to optimize radioprotection. Thin MCP-Ns thermoluminescent dosimeters suitable for measuring beta and gamma radiation were used for extremity dosimetry, active personal dosimeters for whole-body dosimetry. Extremity doses were determined during dispensing of 124I and oral administration of the activity to the patient, the body dose during all phases of the PET/CT procedure. In addition, dose rates of vials and syringes as used in clinical practice were measured. The procedure for dispensing 124I was optimized using newly developed shielding. Skin dose rates up to 100 mSv/min were measured when in contact with the manufacturer's vial containing 370 MBq of 124I. For an unshielded 5 ml syringe the positron skin dose was about seven times the gamma dose. Before optimization of the preparation of 124I, using an already reasonably safe technique, the highest mean skin dose caused by handling 370 MBq was 1.9 mSv (max. 4.4 mSv). After optimization the skin dose was below 0.2 mSv. The highly energetic positrons emitted by 124I can cause high skin doses if radioprotection is poor. Under optimized conditions occupational doses are acceptable. Education of workers is of paramount importance.

  17. Study of the Nuclear Structure of 39P Using Beta-Delayed Gamma Spectroscopy

    Science.gov (United States)

    Abromeit, Brittany; NSCL Experiment E14063 Team Team

    2016-03-01

    Investigation of nuclei with neutron and proton imbalance is at the forefront of nuclear physics research today. This is driven by the fact that the structure in these regimes may vary with that seen near the valley of stability. With eight neutrons more than the stable isotope of phosphorous, 39P is a neutron-rich exotic nucleus that has very limited information on it: previous studies of 39P produce only three known energy levels and gamma rays. The fragmentation of a 48Ca primary beam on a 564mg/cm2 thick Be target at the National Superconducting Cyclotron Laboratory (NSCL) was used to produce exotic 39Si. Using the NSCL Beta Counting System (BCS), consisting of a thick planner germanium double-sided strip detector (GeDSSD) and 16 High-purity germanium detectors in an array, SeGA, the beta-gamma coincidences from the decay of 39Si to 39P were analyzed. The resulting level scheme of 39P, including over 12 new gamma rays and energy states, confirmation of the previously measured half-life, and first-time logft values will be presented. This work was supported by the NSF under Grant No. 1401574.

  18. Effect of beta and gamma neurofeedback on memory and intelligence in the elderly.

    Science.gov (United States)

    Staufenbiel, S M; Brouwer, A-M; Keizer, A W; van Wouwe, N C

    2014-01-01

    Recent research showed a correlation between cognitive decline and a decrease of EEG gamma activity. In the present double-blind randomized control study, we investigated whether gamma and beta neurofeedback protocols, that have been shown to modulate performance on cognitive control and memory in young adults, also leads to increased brain activity and cognitive performance in elderly. Twenty older adults either performed eight 30-min gamma neurofeedback session or beta neurofeedback session within a period of 21 days. Cognitive performance was determined before and after the training through an IQ and memory task and we added a subjective well-being questionnaire. Both neurofeedback training protocols resulted in a significant increase of the brain activity within each training session, suggesting that the aging brain is still trainable. However, we found no effects on cognitive performance or transfer of the feedback beyond the trainings. We discuss several possible reasons for the lack of training on rest measurements and cognition and ways to improve the feedback protocols for future studies. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Temporal Regulation of Natural Killer T Cell Interferon Gamma Responses by β-Catenin-Dependent and -Independent Wnt Signaling.

    Science.gov (United States)

    Kling, Jessica C; Jordan, Margaret A; Pitt, Lauren A; Meiners, Jana; Thanh-Tran, Thao; Tran, Le Son; Nguyen, Tam T K; Mittal, Deepak; Villani, Rehan; Steptoe, Raymond J; Khosrotehrani, Kiarash; Berzins, Stuart P; Baxter, Alan G; Godfrey, Dale I; Blumenthal, Antje

    2018-01-01

    Natural killer T (NKT) cells are prominent innate-like lymphocytes in the liver with critical roles in immune responses during infection, cancer, and autoimmunity. Interferon gamma (IFN-γ) and IL-4 are key cytokines rapidly produced by NKT cells upon recognition of glycolipid antigens presented by antigen-presenting cells (APCs). It has previously been reported that the transcriptional coactivator β-catenin regulates NKT cell differentiation and functionally biases NKT cell responses toward IL-4, at the expense of IFN-γ production. β-Catenin is not only a central effector of Wnt signaling but also contributes to other signaling networks. It is currently unknown whether Wnt ligands regulate NKT cell functions. We thus investigated how Wnt ligands and β-catenin activity shape liver NKT cell functions in vivo in response to the glycolipid antigen, α-galactosylceramide (α-GalCer) using a mouse model. Pharmacologic targeting of β-catenin activity with ICG001, as well as myeloid-specific genetic ablation of Wntless (Wls) , to specifically target Wnt protein release by APCs, enhanced early IFN-γ responses. By contrast, within several hours of α-GalCer challenge, myeloid-specific Wls deficiency, as well as pharmacologic targeting of Wnt release using the small molecule inhibitor IWP-2 impaired α-GalCer-induced IFN-γ responses, independent of β-catenin activity. These data suggest that myeloid cell-derived Wnt ligands drive early Wnt/β-catenin signaling that curbs IFN-γ responses, but that, subsequently, Wnt ligands sustain IFN-γ expression independent of β-catenin activity. Our analyses in ICG001-treated mice confirmed a role for β-catenin activity in driving early IL-4 responses by liver NKT cells. However, neither pharmacologic nor genetic perturbation of Wnt production affected the IL-4 response, suggesting that IL-4 production by NKT cells in response to α-GalCer is not driven by released Wnt ligands. Collectively, these data reveal complex temporal

  20. Temporal Regulation of Natural Killer T Cell Interferon Gamma Responses by β-Catenin-Dependent and -Independent Wnt Signaling

    Directory of Open Access Journals (Sweden)

    Jessica C. Kling

    2018-03-01

    Full Text Available Natural killer T (NKT cells are prominent innate-like lymphocytes in the liver with critical roles in immune responses during infection, cancer, and autoimmunity. Interferon gamma (IFN-γ and IL-4 are key cytokines rapidly produced by NKT cells upon recognition of glycolipid antigens presented by antigen-presenting cells (APCs. It has previously been reported that the transcriptional coactivator β-catenin regulates NKT cell differentiation and functionally biases NKT cell responses toward IL-4, at the expense of IFN-γ production. β-Catenin is not only a central effector of Wnt signaling but also contributes to other signaling networks. It is currently unknown whether Wnt ligands regulate NKT cell functions. We thus investigated how Wnt ligands and β-catenin activity shape liver NKT cell functions in vivo in response to the glycolipid antigen, α-galactosylceramide (α-GalCer using a mouse model. Pharmacologic targeting of β-catenin activity with ICG001, as well as myeloid-specific genetic ablation of Wntless (Wls, to specifically target Wnt protein release by APCs, enhanced early IFN-γ responses. By contrast, within several hours of α-GalCer challenge, myeloid-specific Wls deficiency, as well as pharmacologic targeting of Wnt release using the small molecule inhibitor IWP-2 impaired α-GalCer-induced IFN-γ responses, independent of β-catenin activity. These data suggest that myeloid cell-derived Wnt ligands drive early Wnt/β-catenin signaling that curbs IFN-γ responses, but that, subsequently, Wnt ligands sustain IFN-γ expression independent of β-catenin activity. Our analyses in ICG001-treated mice confirmed a role for β-catenin activity in driving early IL-4 responses by liver NKT cells. However, neither pharmacologic nor genetic perturbation of Wnt production affected the IL-4 response, suggesting that IL-4 production by NKT cells in response to α-GalCer is not driven by released Wnt ligands. Collectively, these data reveal

  1. Suppressor of cytokine signalling-3 inhibits Tumor necrosis factor-alpha induced apoptosis and signalling in beta cells

    DEFF Research Database (Denmark)

    Bruun, Christine; Heding, Peter E; Rønn, Sif G

    2009-01-01

    Tumor necrosis factor-alpha (TNFalpha) is a pro-inflammatory cytokine involved in the pathogenesis of several diseases including type 1 diabetes mellitus (T1DM). TNFalpha in combination with interleukin-1-beta (IL-1beta) and/or interferon-gamma (IFNgamma) induces specific destruction...

  2. Interferon-gamma and tumor necrosis factor-alpha sensitize primarily resistant human endometrial stromal cells to Fas-mediated apoptosis

    DEFF Research Database (Denmark)

    Fluhr, Herbert; Krenzer, Stefanie; Stein, Gerburg M

    2007-01-01

    The subtle interaction between the implanting embryo and the maternal endometrium plays a pivotal role during the process of implantation. Human endometrial stromal cells (ESCs) express Fas and the implanting trophoblast cells secrete Fas ligand (FASLG, FasL), suggesting a possible role for Fas......-mediated signaling during early implantation. Here we show that ESCs are primarily resistant to Fas-mediated apoptosis independently of their state of hormonal differentiation. Pre-treatment of ESCs with interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha sensitizes them to become apoptotic upon stimulation...... of Fas by an agonistic anti-Fas antibody. Incubation of ESCs with the early embryonic signal human chorionic gonadotropin (hCG, CGB) does not influence their reaction to Fas stimulation. The sensitizing effect of IFN-gamma and TNF-alpha was accompanied by a significant upregulation of Fas and FLICE...

  3. Reduction of beta-interference in gamma-spectrometric measurements of neutron-irradiated geological material

    International Nuclear Information System (INIS)

    Garmann, L.B.

    1986-01-01

    The analytical technique for INAA, when applied to geological materials, is improved by introducing an electromagnetic field between sample and detector. This field lowers the bremsstrahlung background intensity in the gamma-spectrum by reducing the number of beta-particles reaching the detector. Thus precision, accuracy and lower detection limit are improved. The technique was used on alkalisyenite and on meteoritic material, rocks containing high quantities of sodium and iron, respectively. After neutron irradiation, the induced nuclides sup(24)Na and sup(59)Fe are responsible for high bremsstrahlung interference, which under normal analyitical conditions would mask any x-ray or gamma-ray peaks of interest. The technique is easily applied to multielement analysis of geological and biological materials. It can be combined with sophisticated spectrum-treating techniques such as spectrum stripping and spectrum smoothing, or coincidence-anticoincidence circuits. (author)

  4. Automatic analysis algorithm for radionuclide pulse-height data from beta-gamma coincidence systems

    International Nuclear Information System (INIS)

    Foltz Biegalski, K.M.

    2001-01-01

    There are two acceptable noble gas monitoring measurement modes for Comprehensive Nuclear-Test-Ban-Treaty (CTBT) verification purposes defined in CTBT/PC/II/WG.B/1. These include beta-gamma coincidence and high-resolution gamma-spectrometry. There are at present no commercial, off-the-shelf (COTS) applications for the analysis of β-γ coincidence data. Development of such software is in progress at the Prototype International Data Centre (PIDC) for eventual deployment at the International Data Centre (IDC). Flowcharts detailing the automatic analysis algorithm for β-γ coincidence data to be coded at the PIDC is included. The program is being written in C with Oracle databasing capabilities. (author)

  5. On evaluated nuclear data for beta-delayed gamma rays following of special nuclear materials

    Energy Technology Data Exchange (ETDEWEB)

    Mencarini, Leonardo de H.; Caldeira, Alexandre D., E-mail: mencarini@ieav.cta.b, E-mail: alexdc@ieav.cta.b [Instituto de Estudos Avancados (IEAv/CTA), Sao Jose dos Campos, SP (Brazil)

    2011-07-01

    In this paper, a new type of information available in ENDF is discussed. During a consistency check of the evaluated nuclear data library ENDF/B-VII.0 performed at the Nuclear Data Subdivision of the Institute for Advanced Studies, the size of the files for some materials drew the attention of one of the authors. Almost 94 % of all available information for these special nuclear materials is used to represent the beta-delayed gamma rays following fission. This is the first time this information is included in an ENDF version. (author)

  6. Thermoluminescent characterization of thin films of aluminium oxide submitted to beta and gamma radiation

    International Nuclear Information System (INIS)

    Villagran, E.; Escobar A, L.; Camps, E.; Gonzalez, P.R.; Martinez A, L.

    2002-01-01

    By mean of the laser ablation technique, thin films of aluminium oxide have been deposited on kapton substrates. These films present thermoluminescent response (Tl) when they are exposed to beta and gamma radiation. The brilliance curves show two peaks between 112 C and 180 C. A dose-response relationship study was realized and the Tl kinetic parameters were determined using the computerized deconvolution of the brilliance curve (CGCD). The thin films of aluminium oxide have potential applications as ultra.thin radiation dosemeters. (Author)

  7. Comparison of new and existing algorithms for the analysis of 2D radioxenon beta gamma spectra

    International Nuclear Information System (INIS)

    Deshmukh, Nikhil; Prinke, Amanda; Miller, Brian; McIntyre, Justin

    2017-01-01

    The aim of this paper is to compare radioxenon beta-gamma analysis algorithms using simulated spectra with experimentally measured background, where the ground truth of the signal is known. We believe that this is among the largest efforts to date in terms of the number of synthetic spectra generated and number of algorithms compared using identical spectra. We generate an estimate for the minimum detectable counts for each isotope using each algorithm. The paper also points out a conceptual model to put the various algorithms into a continuum. Our results show that existing algorithms can be improved and some newer algorithms can be better than the ones currently used. (author)

  8. On evaluated nuclear data for beta-delayed gamma rays following of special nuclear materials

    International Nuclear Information System (INIS)

    Mencarini, Leonardo de H.; Caldeira, Alexandre D.

    2011-01-01

    In this paper, a new type of information available in ENDF is discussed. During a consistency check of the evaluated nuclear data library ENDF/B-VII.0 performed at the Nuclear Data Subdivision of the Institute for Advanced Studies, the size of the files for some materials drew the attention of one of the authors. Almost 94 % of all available information for these special nuclear materials is used to represent the beta-delayed gamma rays following fission. This is the first time this information is included in an ENDF version. (author)

  9. Design and operation of a prototype incinerator for beta-gamma waste

    International Nuclear Information System (INIS)

    Farber, M.G.; Hootman, H.E.; Becker, G.W. Jr.; Makohon, P.A.

    1981-01-01

    A full-scale test incinerator has been built at the Savannah River Laboratory to provide a design basis for a radioactive facility that will burn low-level beta-gamma contaminated waste. The processing steps include waste feed loading, incineration, ash residue packaging, and off-gas cleanup. Both solid and liquid waste will be incinerated during the test program. The components of the solid waste are cellulose, latex, polyethylene, and PVC; the solvent is composed of n-paraffin and TBP. A research program will confirm the feasibility of the design and determine the operating parameters

  10. Interferon alpha treatment stimulates interferon gamma expression in type I NKT cells and enhances their antiviral effect against hepatitis C virus.

    Science.gov (United States)

    Miyaki, Eisuke; Hiraga, Nobuhiko; Imamura, Michio; Uchida, Takuro; Kan, Hiromi; Tsuge, Masataka; Abe-Chayama, Hiromi; Hayes, C Nelson; Makokha, Grace Naswa; Serikawa, Masahiro; Aikata, Hiroshi; Ochi, Hidenori; Ishida, Yuji; Tateno, Chise; Ohdan, Hideki; Chayama, Kazuaki

    2017-01-01

    Interferon (IFN) inhibits hepatitis C virus (HCV) replication through up-regulation of intrahepatic IFN-stimulated gene expression but also through activation of host immune cells. In the present study, we analyzed the immune cell-mediated antiviral effects of IFN-α using HCV-infected mice. Urokinase-type plasminogen activator (uPA)-severe combined immunodeficiency (SCID) mice with transplanted human hepatocytes were infected with genotype 1b HCV and injected with human peripheral blood mononuclear cells (PBMCs). IFN-α treatment following human PBMC transplantation resulted in a significant reduction in serum HCV RNA titers and a higher human CD45-positive mononuclear cell chimerism compared to mice without human PBMC transplantation. In mice with human PBMCs treated with IFN-α, serum concentrations of IFN-γ increased, and natural killer T (NKT) cells, especially type I NKT cells, produced IFN-γ. Mice in which IFN-γ signaling was blocked using antibody or in which transplanted PBMCs were depleted for type I NKT cells showed similar levels of anti-HCV effect compared with mice treated only with IFN-α. These results show that IFN-α stimulates IFN-γ expression in type 1 NKT cells and enhances the inhibition of HCV replication. We propose that type 1 NKT cells might represent a new therapeutic target for chronic hepatitis C patients.

  11. Pulmonary Immune-Compartment-Specific Interferon Gamma Responses in HIV-Infected Individuals with Active Tuberculosis (TB in an Area of High TB Prevalence

    Directory of Open Access Journals (Sweden)

    S. Buldeo

    2012-01-01

    Full Text Available There is a paucity of data on the pulmonary immune-compartment interferon gamma (IFNγ response to M. tuberculosis, particularly in settings of high tuberculosis (TB prevalence and in HIV-coinfected individuals. This data is necessary to understand the diagnostic potential of commercially available interferon gamma release assays (IGRAs in both the pulmonary immune-compartment and peripheral blood. We used intracellular cytokine staining by flow cytometry to assess the IFNγ response to purified protein derivative (PPD and early secretory antigen 6 (ESAT6 in induced sputa (ISp and blood samples from HIV-infected, smear-negative, TB suspects. We found that individuals with active TB disease produced significantly less IFNγ in response to PPD in their induced sputa samples than individuals with non-active TB (control group. This difference was not reflected in the peripheral blood, even within the CD27− CD4+ memory T lymphocyte population. These findings suggest that progression to active TB disease may be associated with the loss of IFNγ secretion at the site of primary infection. Our findings highlight the importance of studying pulmonary immune-compartment M. tuberculosis specific responses to elucidate IFNγ secretion across the spectrum of TB disease.

  12. Proinflammatory cytokines tumor necrosis factor-alpha and interferon-gamma alter tight junction structure and function in the rat parotid gland Par-C10 cell line.

    Science.gov (United States)

    Baker, Olga J; Camden, Jean M; Redman, Robert S; Jones, Jonathan E; Seye, Cheikh I; Erb, Laurie; Weisman, Gary A

    2008-11-01

    Sjögren's syndrome (SS) is an autoimmune disorder characterized by inflammation and dysfunction of salivary glands, resulting in impaired secretory function. The production of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) is elevated in exocrine glands of patients with SS, although little is known about the effects of these cytokines on salivary epithelial cell functions necessary for saliva secretion, including tight junction (TJ) integrity and the establishment of transepithelial ion gradients. The present study demonstrates that chronic exposure of polarized rat parotid gland (Par-C10) epithelial cell monolayers to TNF-alpha and IFN-gamma decreases transepithelial resistance (TER) and anion secretion, as measured by changes in short-circuit current (I(sc)) induced by carbachol, a muscarinic cholinergic receptor agonist, or UTP, a P2Y(2) nucleotide receptor agonist. In contrast, TNF-alpha and IFN-gamma had no effect on agonist-induced increases in the intracellular calcium concentration [Ca(2+)](i) in Par-C10 cells. Furthermore, treatment of Par-C10 cell monolayers with TNF-alpha and IFN-gamma increased paracellular permeability to normally impermeant proteins, altered cell and TJ morphology, and downregulated the expression of the TJ protein, claudin-1, but not other TJ proteins expressed in Par-C10 cells. The decreases in TER, agonist-induced transepithelial anion secretion, and claudin-1 expression caused by TNF-alpha, but not IFN-gamma, were reversible by incubation of Par-C10 cell monolayers with cytokine-free medium for 24 h, indicating that IFN-gamma causes irreversible inhibition of cellular activities associated with fluid secretion in salivary glands. Our results suggest that cytokine production is an important contributor to secretory dysfunction in SS by disrupting TJ integrity of salivary epithelium.

  13. Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial

    DEFF Research Database (Denmark)

    Kappos, Ludwig; Freedman, Mark S; Polman, Chris H

    2009-01-01

    with interferon beta-1b on time to clinically definite multiple sclerosis (CDMS) and other disease outcomes, including disability progression. METHODS: Patients with a first event suggestive of multiple sclerosis and a minimum of two clinically silent lesions in MRI were randomly assigned to receive interferon...... index (FAMS-TOI) at 5 years. Analysis of the primary endpoints was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00185211. FINDINGS: 235 (80%) patients from the early treatment and 123 (70%) from the delayed treatment group completed the 5-year study. Early treatment...

  14. Dual specific oral tolerance induction using interferon gamma for IgE-mediated anaphylactic food allergy and the dissociation of local skin allergy and systemic oral allergy: tolerance or desensitization?

    Science.gov (United States)

    Noh, G; Jang, E H

    2014-01-01

    Specific oral tolerance induction (SOTI) for IgE-mediated food allergy (IFA) can be successfully achieved using interfero gamma (classic SOTI). In this study, a tolerable dose was introduced during tolerance induction with interferon gamma (dual SOTI), and its effectiveness was evaluated. The study population comprised 25 IFA patients. Blood samples were taken for analysis, including complete blood count with differential counts of eosinophils, serum total IgE levels, and specific IgE for allergenic foods. Skin prick tests were conducted with the allergens. Oral food challenges were performed to diagnose IFA. Ten patients received dual SOTI, 5 received classic SOTI, 5 received SOTI without interferon gamma (original SOTI), and 5 were not treated (controls). Patients treated with dual SOTI and classic SOTI using interferon gamma became tolerant to the allergenic food. The tolerable dose was introduced successfully in dual SOTI. It was difficult to proceed with the same dosing protocol used for classic SOTI in cases treated with original SOTI. Following dual SOTI, the systemic reaction to oral intake subsided, but the local skin reaction to contact with the allergenic food persisted. Dual SOTI is an improved protocol for SOTI using interferon gamma for IFA.The local skin reaction and systemic reaction to oral intake were dissociated following dual SOTI. In cases of food allergy, tolerance appears to result from desensitization to allergens.

  15. Candidate Gene Study of TRAIL and TRAIL Receptors: Association with Response to Interferon Beta Therapy in Multiple Sclerosis Patients

    Science.gov (United States)

    Órpez-Zafra, Teresa; Pinto-Medel, María Jesús; Oliver-Martos, Begoña; Ortega-Pinazo, Jesús; Arnáiz, Carlos; Guijarro-Castro, Cristina; Varadé, Jezabel; Álvarez-Lafuente, Roberto; Urcelay, Elena; Sánchez-Jiménez, Francisca

    2013-01-01

    TRAIL and TRAIL Receptor genes have been implicated in Multiple Sclerosis pathology as well as in the response to IFN beta therapy. The objective of our study was to evaluate the association of these genes in relation to the age at disease onset (AAO) and to the clinical response upon IFN beta treatment in Spanish MS patients. We carried out a candidate gene study of TRAIL, TRAILR-1, TRAILR-2, TRAILR-3 and TRAILR-4 genes. A total of 54 SNPs were analysed in 509 MS patients under IFN beta treatment, and an additional cohort of 226 MS patients was used to validate the results. Associations of rs1047275 in TRAILR-2 and rs7011559 in TRAILR-4 genes with AAO under an additive model did not withstand Bonferroni correction. In contrast, patients with the TRAILR-1 rs20576-CC genotype showed a better clinical response to IFN beta therapy compared with patients carrying the A-allele (recessive model: p = 8.88×10−4, pc = 0.048, OR = 0.30). This SNP resulted in a non synonymous substitution of Glutamic acid to Alanine in position 228 (E228A), a change previously associated with susceptibility to different cancer types and risk of metastases, suggesting a lack of functionality of TRAILR-1. In order to unravel how this amino acid change in TRAILR-1 would affect to death signal, we performed a molecular modelling with both alleles. Neither TRAIL binding sites in the receptor nor the expression levels of TRAILR-1 in peripheral blood mononuclear cell subsets (monocytes, CD4+ and CD8+ T cells) were modified, suggesting that this SNP may be altering the death signal by some other mechanism. These findings show a role for TRAILR-1 gene variations in the clinical outcome of IFN beta therapy that might have relevance as a biomarker to predict the response to IFN beta in MS. PMID:23658636

  16. Candidate gene study of TRAIL and TRAIL receptors: association with response to interferon beta therapy in multiple sclerosis patients.

    Directory of Open Access Journals (Sweden)

    Carlos López-Gómez

    Full Text Available TRAIL and TRAIL Receptor genes have been implicated in Multiple Sclerosis pathology as well as in the response to IFN beta therapy. The objective of our study was to evaluate the association of these genes in relation to the age at disease onset (AAO and to the clinical response upon IFN beta treatment in Spanish MS patients. We carried out a candidate gene study of TRAIL, TRAILR-1, TRAILR-2, TRAILR-3 and TRAILR-4 genes. A total of 54 SNPs were analysed in 509 MS patients under IFN beta treatment, and an additional cohort of 226 MS patients was used to validate the results. Associations of rs1047275 in TRAILR-2 and rs7011559 in TRAILR-4 genes with AAO under an additive model did not withstand Bonferroni correction. In contrast, patients with the TRAILR-1 rs20576-CC genotype showed a better clinical response to IFN beta therapy compared with patients carrying the A-allele (recessive model: p = 8.88×10(-4, pc = 0.048, OR = 0.30. This SNP resulted in a non synonymous substitution of Glutamic acid to Alanine in position 228 (E228A, a change previously associated with susceptibility to different cancer types and risk of metastases, suggesting a lack of functionality of TRAILR-1. In order to unravel how this amino acid change in TRAILR-1 would affect to death signal, we performed a molecular modelling with both alleles. Neither TRAIL binding sites in the receptor nor the expression levels of TRAILR-1 in peripheral blood mononuclear cell subsets (monocytes, CD4+ and CD8+ T cells were modified, suggesting that this SNP may be altering the death signal by some other mechanism. These findings show a role for TRAILR-1 gene variations in the clinical outcome of IFN beta therapy that might have relevance as a biomarker to predict the response to IFN beta in MS.

  17. Effects of tumor necrosis factor-alpha and interferon-gamma on expressions of matrix metalloproteinase-2 and -9 in human bladder cancer cells.

    Science.gov (United States)

    Shin, K Y; Moon, H S; Park, H Y; Lee, T Y; Woo, Y N; Kim, H J; Lee, S J; Kong, G

    2000-10-31

    We have investigated the effects of tumor necrosis factor-alpha (TNF-alpha) and interferon (INF-gamma), the potent Bacillus Calmette-Guerin (BCG)-induced cytokines on the production of MMP-2, MMP-9, TIMP-1, TIMP-2 and MT1-MMP in high grade human bladder cancer cell lines, T-24, J-82 and HT-1376 cell lines. MMP-2 expression and activity were decreased in T-24 cells treated with both cytokines in a dose dependent manner. However, J-82 cells treated with TNF-alpha and INF-gamma revealed dose dependent increases of MMP-9 expression and activity with similar baseline expression and activity of MMP-2. HT-1376 cells after exposure to TNF-alpha only enhanced the expression and activity of MMP-9. These results indicate that TNF-alpha and INF-gamma could regulate the production of MMP-2 or MMP-9 on bladder cancer cells and their patterns of regulation are cell specific. Furthermore, this diverse response of bladder cancer cells to TNF-alpha and INF-gamma suggests that BCG immunotherapy may enhance the invasiveness of bladder cancer in certain conditions with induction of MMPs.

  18. Measurement of the beta-gamma directional correlation of the transition 46Sc→46Ti

    International Nuclear Information System (INIS)

    Krexner, G.

    1978-01-01

    Measuring the forward - backward asymmetry of the direction of gamma quanta with respect to the direction of a preceding beta particle emission is one of the methods which have been developed over the past twenty years to investigate parity admixtures in nuclear states. Both theoretical calculations and experiments using this method yield very small values for the considered effect. Moreover the accuracy is limited for statistical reasons. Hence there exists a fundamental interest in proving the experimental arrangement to be free of systematic errors. The subject of this work is an experiment checking a six - detector apparatus which has been used to investigate the beta - gamma directional correlation in the decay 203 Hg→ 203 Tl. For the control measurement the transition 46 Sc→ 46 Ti was chosen. The asymmetry coefficient should yield zero and thus furnish evidence of the absence of systematic errors. The necessary 46 Sc source had to meet very restricting requirements. The feasibility of various methods for producing radioactive samples was reviewed; finally a specially designed high vacuum evaporation plant was constructed. The concept of this device and the preparation of the source are dealt with in detail. A preliminary result of the control experiment is given. However, at present a definite interpretation of the obtained values is not possible. (author)

  19. Study of Optically Stimulated Luminescence of LiF:Mg,Ti for beta and gamma dosimetry

    International Nuclear Information System (INIS)

    Matsushima, Luciana C.; Veneziani, Glauco R.; Campos, Letícia L.

    2013-01-01

    Modern advances in radiation medicine – radiodiagnosis, radiotherapy and interventional radiography – each present dosimetry challenges for the medical physicist that did not exist previously. In all of these areas a constant balance has to be made between the treatment necessary to destroy the tumor and the unnecessary exposure of healthy tissue. Innovative applications of OSL dosimetry are now appearing in each of these areas to help the medical physicist and oncologist design the most effective, and least deleterious, treatment for their patients. High sensitivity, precise delivery of light, fast readout times, simpler readers and easier automation are the main advantages of OSL in comparison with TLD. This work aimed to study the application of OSL technique using lithium fluoride dosimeters doped with magnesium and titanium (LiF:Mg,Ti) for application in beta and gamma dosimetry. -- Highlights: •Study of Optically Stimulated Luminescence of LiF:Mg,Ti and microLiF:Mg,Ti. •OSL response of TLD-100 dosimeters to beta and gamma radiation. •Analysis of repeatability and lowest levels of detection of detectors LiF:Mg,Ti

  20. Durability and shielding performance of borated Ceramicrete coatings in beta and gamma radiation fields

    Energy Technology Data Exchange (ETDEWEB)

    Wagh, Arun S., E-mail: asw@anl.gov [Environmental Science Division, Argonne National Laboratory, 9700 S. Cass Avenue, Argonne, IL 60439 (United States); Sayenko, S.Yu.; Dovbnya, A.N.; Shkuropatenko, V.A.; Tarasov, R.V.; Rybka, A.V.; Zakharchenko, A.A. [National Science Center, Kharkov Institute of Physics and Technology, Kharkov (Ukraine)

    2015-07-15

    Highlights: • It incorporates all suggestions by the reviewers. • Explanation to each new term is provided and suitable references are given. • Sample identities have been streamlined by revising the text and the tables. • Some figures have been redrawn. - Abstract: Ceramicrete™, a chemically bonded phosphate ceramic, was developed for nuclear waste immobilization and nuclear radiation shielding. Ceramicrete products are fabricated by an acid–base reaction between magnesium oxide and mono potassium phosphate. Fillers are used to impart desired properties to the product. Ceramicrete’s tailored compositions have resulted in several commercial structural products, including corrosion- and fire-protection coatings. Their borated version, called Borobond™, has been studied for its neutron shielding capabilities and is being used in structures built for storage of nuclear materials. This investigation assesses the durability and shielding performance of borated Ceramicrete coatings when exposed to gamma and beta radiations to predict the composition needed for optimal shielding performance in a realistic nuclear radiation field. Investigations were conducted using experimental data coupled with predictive Monte Carlo computer model. The results show that it is possible to produce products for simultaneous shielding of all three types of nuclear radiations, viz., neutrons, gamma-, and beta-rays. Additionally, because sprayable Ceramicrete coatings exhibit excellent corrosion- and fire-protection characteristics on steel, this research also establishes an opportunity to produce thick coatings to enhance the shielding performance of corrosion and fire protection coatings for use in high radiation environment in nuclear industry.

  1. A novel needle for subcutaneous injection of interferon beta-1a: effect on pain in volunteers and satisfaction in patients with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Prais Wes A

    2008-10-01

    Full Text Available Abstract Background To reduce injection pain and improve satisfaction, a thinner (29-gauge [29G], sharper (5-bevel needle than the 27G/3-bevel needle used previously to inject interferon (IFN beta-1a, 44 or 22 mcg subcutaneously (sc three times weekly (tiw, was developed for use in multiple sclerosis (MS. Methods Two clinical trials in healthy volunteers and five surveys of patients with MS were conducted to assess whether the 29G/5-bevel needle with a Thermo Plastic Elastomer (TPE needle shield (a sleeve that houses the tip of the needle in a secure location is an improvement over the 27G/3-bevel needle with a rubber shield for injection of IFN beta-1a, 44 or 22 mcg sc tiw. Parameters assessed were: pain and ease of insertion (healthy volunteer and nurse responses on subjective pain measurement scales; and patient satisfaction (surveys of patients with MS. Results In healthy volunteers, the 29G/5-bevel needle with TPE shield was associated with the least perceived pain on the Visual Analog Scale (VAS and Verbal VAS (VB-VAS; mean VAS pain scores decreased by 40% and skin penetration improved by 69% compared with the 27G/3-bevel needle with standard rubber shield (p Conclusion Together these studies indicate that the 29G/5-bevel needle with the TPE shield is an improvement over the 27G/3-bevel needle with standard rubber shield in terms of pain, ease of insertion and patient satisfaction. These improvements are expected to result in improved compliance in patients with MS treated with IFN beta-1a, 44 or 22 mcg sc tiw.

  2. The effect of co-administration of DNA carrying chicken interferon-gamma gene on protection of chickens against infectious bursal disease by DNA-mediated vaccination.

    Science.gov (United States)

    Hsieh, Ming Kun; Wu, Ching Ching; Lin, Tsang Long

    2006-11-17

    The purpose of the present study was to determine whether DNA vaccination by co-administration of DNA coding for chicken interferon-gamma (IFN-gamma) gene and DNA encoding for the VP243 gene of IBDV could enhance immune response and protection efficacy of chickens against challenge by IBDV. Plasmids carrying VP243 gene of IBDV strain variant E (VE) (P/VP243/E) and chicken IFN-gamma gene (P/cIFN-gamma) were constructed, respectively. One-day-old chickens were intramuscularly injected with P/VP243/E, or P/cIFN-gamma, or both once, twice, or three times into the thigh muscle of one leg or the thigh muscles of two separate legs at weekly intervals. Chickens were orally challenged with IBDV strain VE at 3 weeks of age and observed for 10 days. Chickens receiving two plasmids in the same site two times had significantly higher (Pprotection and those receiving two plasmids in the same sites did not have any protection against IBD. The enzyme-linked immunosorbent assay (ELISA) and virus neutralization (VN) titers to IBDV of chickens in the groups with three doses of P/VP243/E were significantly higher (Pprotected by DNA vaccination did not have detectable IBDV antigen in the bursae as determined by immunofluorescent antibody assay (IFA). The results indicated that co-administration of plasmid encoding chicken IFN-gamma gene with plasmid encoding a large segment gene of the IBDV did not enhance immune response and protection against challenge by IBDV.

  3. Tuberculin skin testing and treatment modulates interferon-gamma release assay results for latent tuberculosis in migrants.

    Directory of Open Access Journals (Sweden)

    Matthew K O'Shea

    Full Text Available Identifying latent tuberculosis infection (LTBI in people migrating from TB endemic regions to low incidence countries is an important control measure. However, no prospective longitudinal comparisons between diagnostic tests used in such migrant populations are available.To compare commercial interferon (IFN-gamma release assays (IGRAs and the tuberculin skin test (TST for diagnosing LTBI in a migrant population, and the influence of antecedent TST and LTBI treatment on IGRA performance.This cohort study, performed from February to September 2012, assessed longitudinal IGRA and TST responses in Nepalese military recruits recently arrived in the UK. Concomitant T-SPOT.TB, QFT-GIT and TST were performed on day 0, with IGRAs repeated 7 and 200 days later, following treatment for LTBI if necessary.166 Nepalese recruits were prospectively assessed. At entry, 21 individuals were positive by T-SPOT.TB and 8 individuals by QFT-GIT. There was substantial agreement between TST and T-SPOT.TB positives at baseline (71.4% agreement; κ = 0.62; 95% CI:0.44-0.79, but only moderate concordance between positive IGRAs (38.1% agreement; κ = 0.46; 95% CI:0.25-0.67. When reassessed 7 days following TST, numbers of IGRA-positive individuals changed from 8 to 23 for QFT-GIT (p = 0.0074 and from 21 to 23 for T-SPOT.TB (p = 0.87. This resulted in an increase in IGRA concordance to substantial (64.3% agreement; κ = 0.73; 95% CI:0.58-0.88. Thus, in total on day 0 and day 7 after testing, 29 out of 166 participants (17.5% provided a positive IGRA and of these 13 were TST negative. Two hundred days after the study commenced and three months after treatment for LTBI was completed by those who were given chemoprophylaxis, 23 and 21 participants were positive by T-SPOT.TB or QFT-GIT respectively. When individual responses were examined longitudinally within this population 35% of the day 7 QFT-GIT-positive, and 19% T-SPOT.TB-positive individuals, were

  4. Interferon-gamma release assay for the diagnosis of latent tuberculosis infection: A latent-class analysis.

    Directory of Open Access Journals (Sweden)

    Tan N Doan

    Full Text Available Accurate diagnosis and subsequent treatment of latent tuberculosis infection (LTBI is essential for TB elimination. However, the absence of a gold standard test for diagnosing LTBI makes assessment of the true prevalence of LTBI and the accuracy of diagnostic tests challenging. Bayesian latent class models can be used to make inferences about disease prevalence and the sensitivity and specificity of diagnostic tests using data on the concordance between tests. We performed the largest meta-analysis to date aiming to evaluate the performance of tuberculin skin test (TST and interferon-gamma release assays (IGRAs for LTBI diagnosis in various patient populations using Bayesian latent class modelling.Systematic search of PubMeb, Embase and African Index Medicus was conducted without date and language restrictions on September 11, 2017 to identify studies that compared the performance of TST and IGRAs for LTBI diagnosis. Two IGRA methods were considered: QuantiFERON-TB Gold In Tube (QFT-GIT and T-SPOT.TB. Studies were included if they reported 2x2 agreement data between TST and QFT-GIT or T-SPOT.TB. A Bayesian latent class model was developed to estimate the sensitivity and specificity of TST and IGRAs in various populations, including immune-competent adults, immune-compromised adults and children. A TST cut-off value of 10 mm was used for immune-competent subjects and 5 mm for immune-compromised individuals.A total of 157 studies were included in the analysis. In immune-competent adults, the sensitivity of TST and QFT-GIT were estimated to be 84% (95% credible interval [CrI] 82-85% and 52% (50-53%, respectively. The specificity of QFT-GIT was 97% (96-97% in non-BCG-vaccinated and 93% (92-94% in BCG-vaccinated immune-competent adults. The estimated figures for TST were 100% (99-100% and 79% (76-82%, respectively. T-SPOT.TB has comparable specificity (97% for both tests and better sensitivity (68% versus 52% than QFT-GIT in immune-competent adults

  5. Vibrational and chiroptical spectroscopic characterization of gamma-turn model cyclic tetrapeptides containing two beta-Ala residues.

    Science.gov (United States)

    Vass, Elemér; Majer, Zsuzsa; Kohalmy, Krisztina; Hollósi, Miklós

    2010-08-01

    The optical spectroscopic characterization of gamma-turns in solution is uncertain and their distinction from beta-turns is often difficult. This work reports systematic ECD and vibrational circular dichroism (VCD) spectroscopic studies on gamma-turn model cyclic tetrapeptides cyclo(Ala-beta-Ala-Pro-beta-Ala) (1), cyclo(Pro-beta-Ala-Pro-beta-Ala) (2) and cyclo(Ala-beta-Ala-Ala-beta-Ala) (3). Conformational analysis performed at the 6-31G(d)/B3LYP level of theory using an adequate PCM solvent model predicted one predominant conformer for 1-3, featuring two inverse gamma-turns. The ECD spectra in ACN of 1 and 2 are characterized by a negative n-->pi* band near 230 nm and a positive pi-->pi* band below 200 nm with a long wavelength shoulder. The ECD spectra in TFE of 1-3 show similar spectra with blue-shifted bands. The VCD spectra in ACN-d(3) of 1 and 2 show a +/-/+/- amide I sign pattern resulting from four uncoupled vibrations in the case of 1 and a sequence of two positive couplets in the case of 2. A -/+/+/- amide I VCD pattern was measured for 3 in TFE-d(2). All three peptides give a positive couplet or couplet-like feature (+/-) in the amide II region. VCD spectroscopy, in agreement with theoretical calculations revealed that low frequency amide I vibrations (at approximately 1630 cm(-1) or below) are indicative of a C(7) H-bonded inverse gamma-turns with Pro in position 2, while gamma-turns encompassing Ala absorb at higher frequency (above 1645 cm(-1)). Copyright 2010 Wiley-Liss, Inc.

  6. Thermodynamics in Neurodegenerative Diseases: Interplay Between Canonical WNT/Beta-Catenin Pathway-PPAR Gamma, Energy Metabolism and Circadian Rhythms.

    Science.gov (United States)

    Vallée, Alexandre; Lecarpentier, Yves; Guillevin, Rémy; Vallée, Jean-Noël

    2018-03-23

    Entropy production rate is increased by several metabolic and thermodynamics abnormalities in neurodegenerative diseases (NDs). Irreversible processes are quantified by changes in the entropy production rate. This review is focused on the opposing interactions observed in NDs between the canonical WNT/beta-catenin pathway and PPAR gamma and their metabolic and thermodynamic implications. In amyotrophic lateral sclerosis and Huntington's disease, WNT/beta-catenin pathway is upregulated, whereas PPAR gamma is downregulated. In Alzheimer's disease and Parkinson's disease, WNT/beta-catenin pathway is downregulated while PPAR gamma is upregulated. The dysregulation of the canonical WNT/beta-catenin pathway is responsible for the modification of thermodynamics behaviors of metabolic enzymes. Upregulation of WNT/beta-catenin pathway leads to aerobic glycolysis, named Warburg effect, through activated enzymes, such as glucose transporter (Glut), pyruvate kinase M2 (PKM2), pyruvate dehydrogenase kinase 1(PDK1), monocarboxylate lactate transporter 1 (MCT-1), lactic dehydrogenase kinase-A (LDH-A) and inactivation of pyruvate dehydrogenase complex (PDH). Downregulation of WNT/beta-catenin pathway leads to oxidative stress and cell death through inactivation of Glut, PKM2, PDK1, MCT-1, LDH-A but activation of PDH. In addition, in NDs, PPAR gamma is dysregulated, whereas it contributes to the regulation of several key circadian genes. NDs show many dysregulation in the mediation of circadian clock genes and so of circadian rhythms. Thermodynamics rhythms operate far-from-equilibrium and partly regulate interactions between WNT/beta-catenin pathway and PPAR gamma. In NDs, metabolism, thermodynamics and circadian rhythms are tightly interrelated.

  7. Right frontal gamma and beta band enhancement while solving a spatial puzzle with insight.

    Science.gov (United States)

    Rosen, A; Reiner, M

    2017-12-01

    Solving a problem with an "a-ha" effect is known as insight. Unlike incremental problem solving, insight is sudden and unique, and the question about its distinct brain activity, intrigues many researchers. In this study, electroencephalogram signals were recorded from 12 right handed, human participants before (baseline) and while they solved a spatial puzzle known as the '10 coin puzzle' that could be solved incrementally or by insight. Participants responded as soon as they reached a solution and reported whether the process was incremental or by sudden insight. EEG activity was recorded from 19 scalp locations. We found significant differences between insight and incremental solvers in the Gamma and Beta 2 bands in frontal areas (F8) and in the alpha band in right temporal areas (T6). The right-frontal gamma indicates a process of restructuring which leads to an insight solution, in spatial problems, further suggesting a universal role of gamma in restructuring. These results further suggest that solving a spatial puzzle via insight requires exclusive brain areas and neurological-cognitive processes which may be important for meta-cognitive components of insight solutions, including attention and monitoring of the solution. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Beta, gamma contamination analysis of thermo luminescence dosimeter cassettes using Geiger Muller counting set up and gamma spectrometry techniques

    International Nuclear Information System (INIS)

    Prasad, S.K.; Sudheer, T.S.; Sahoo, L.; Vinayagam, Bhakti; Kamble, Mahesh; Khuspe, R.R.; Anilkumar, Rekha; Verma, K.K.

    2009-01-01

    Β-γ contamination cheek up of TLD cassettes were carried out and the isotopes found were 137 Cs, 106 Ru, 60 Co, 64 Cu, 144 Ce and 95 Nb with activity per square cm varying from 0.05-4.70 Bq/cm 2 with median value 1.3. The assessed dose in TLD was in the range of 2.10 mSv to 22.05 mSv for beta, 0.05 mSv to 5.25 mSv for gamma. The beta doses have median value of 6.19 mSv. This contamination may be due to active water contamination on TLD's of personnel working for irradiated fuel handling or work in fuel rod (under water) storage area. This gives a method to estimate skin exposure of personnel due to skin contamination during work. Chances of getting TLD's contaminated due to various reasons were studied. Contamination was found maximum inside the cassette box having area 16 cm 2 . In case of plastic pouch of TLD disc contamination was detected in three cases. Contamination level on TLD cassettes using GM counter was found in the range of 0.30-3.6 Bq/cm 2 for cassettes. By opening the window of the surveymeter contamination and field of these cassettes in closed condition were found to increase by 20% due to the measurement of beta dose. With the same condition contamination of TLD cassette in open condition was found five times more. This is due to the a-contamination which is five times more than a contamination, The most prominent isotope 137 Cs in common chemical forms are soluble in water and if inhaled or ingested are rapidly and completely absorbed in the lungs and across the gastrointestinal tract. Thus a skin contamination of most prominent isotope 137 Cs can lead to intake in addition to skin dose. Fading studies of contamination of TLD cassettes were carried out. It was found negligible after counting with GM counting set up after a period of 3 months. But one of the TLD cassettes was showing an 80% reduction of contamination after 3 months with GM counting set up, the contaminants being 141 Ce, 103 Ru and 95 Nb. The gamma peaks in the external exposure

  9. Chemokine receptor CCR5 in interferon-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Kristiansen, T B; Wittenhagen, P

    2007-01-01

    To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta).......To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta)....

  10. ExtaviJect® 30G device for subcutaneous self-injection of interferon beta-1b for multiple sclerosis: a prospective European study

    Directory of Open Access Journals (Sweden)

    Boeru G

    2013-11-01

    Full Text Available Gabriel Boeru,1 Ivan Milanov,2 Francesca De Robertis,3 Wojciech Kozubski,4 Michael Lang,5 Sònia Rojas-Farreras,6 Mark Tomlinson7 1Military Hospital, Bucharest, Romania; 2University Hospital Saint Naum, Sofia, Bulgaria; 3Department of Neurology, Vito Fazzi Hospital of Lecce, Lecce, Italy; 4Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland; 5NeuroPoint Patient Academy and Neurological Practice, Ulm, Germany; 6IMS Health, Barcelona, Spain; 7Novartis Pharma AG, Basel, Switzerland Background: The ExtaviJect® 30G autoinjector was developed to facilitate parenteral self-administration of interferon beta-1b (Extavia®, a first-line disease-modifying therapy in patients with multiple sclerosis. Our aim was to assess patient compliance with treatment when using the autoinjector, patients' and nurses' experiences of using the device, its tolerability, and patient satisfaction. Methods: This was a 12-week, real-world, prospective, observational, noninterventional study conducted in nine European countries. Questionnaires were used to measure patient compliance and to assess patients' and nurses' experiences. All adverse events were recorded by severity, including injection site reactions or pain. Patient satisfaction and health-related quality of life were assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9 and EuroQol-5 Dimension (EQ-5D instruments, respectively. Results: Of 582 patients enrolled, 568 (98% received at least one injection and attended the first follow-up visit at 6 weeks, and 542 (93% attended the second follow-up visit at 12 weeks. For the whole study, 548 of 568 (97% patients were compliant with treatment. Among the various questions assessing whether the device was easy and quick to use accurately, without fear of the needle, 56%–98% of patients and 59%–98% of nurses were in agreement. There were nine serious adverse events (four disease-related reported among the 227 (39

  11. Chemotherapeutics and radiation stimulate MHC class I expression through elevated interferon-beta signaling in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Shan Wan

    Full Text Available Low doses of anticancer drugs have been shown to enhance antitumor immune response and increase the efficacy of immunotherapy. The molecular basis for such effects remains elusive, although selective depletion of T regulatory cells has been demonstrated. In the current studies, we demonstrate that topotecan (TPT, a topoisomerase I-targeting drug with a well-defined mechanism of action, stimulates major histocompatibility complex class I (MHC I expression in breast cancer cells through elevated expression/secretion of interferon-β (IFN-β and activation of type I IFN signaling. First, we show that TPT treatment elevates the expression of both total and cell-surface MHC I in breast cancer cells. Second, conditioned media from TPT-treated breast cancer ZR-75-1 cells induce elevated expression of cell-surface MHC I in drug-naïve recipient cells, suggesting the involvement of cytokines and/or other secreted molecules. Consistently, TPT-treated cells exhibit elevated expression of multiple cytokines such as IFN-β, TNF-α, IL-6 and IL-8. Third, either knocking down the type I interferon receptor subunit 1 (IFNAR1 or addition of neutralizing antibody against IFN-β results in reduced MHC I expression in TPT-treated cells. Together, these results suggest that TPT induces increased IFN-β autocrine/paracrine signaling through type I IFN receptor, resulting in the elevated MHC I expression in tumor cells. Studies have also demonstrated that other chemotherapeutic agents (e.g. etoposide, cisplatin, paclitaxel and vinblastine similarly induce increased IFN-β secretion and elevated MHC I expression. In addition, conditioned media from γ-irradiated donor cells are shown to induce IFN-β-dependent MHC I expression in unirradiated recipient cells. In the aggregate, our results suggest that many cancer therapeutics induce elevated tumor antigen presentation through MHC I, which could represent a common mechanism for enhanced antitumor immune response through

  12. The Critical, Clinical Role of Interferon-Beta in Regulating Cancer Stem Cell Properties in Triple-Negative Breast Cancer.

    Science.gov (United States)

    Doherty, Mary R; Jackson, Mark W

    2018-05-11

    Triple-negative breast cancer (TNBC) the deadliest form of this disease currently lacks a targeted therapy and is characterized by increased risk of metastasis and presence of therapeutically resistant cancer stem cells (CSC). Recent evidence has demonstrated that the presence of an interferon (IFN)/signal transducer of activated transcription 1 (STAT1) gene signature correlates with improved therapeutic response and overall survival in TNBC patients. In agreement with these clinical observations, our recent work has demonstrated, in a cell model of TNBC that CSC have intrinsically repressed IFN signaling. Administration of IFN-β represses CSC properties, inducing a less aggressive non-CSC state. Moreover, an elevated IFN-β gene signature correlated with repressed CSC-related genes and an increased presence of tumor-infiltrating lymphocytes in TNBC specimens. We therefore propose that IFN-β be considered as a potential therapeutic option in the treatment of TNBC, to repress the CSC properties responsible for therapy failure. Future studies aim to improve methods to target delivery of IFN-β to tumors, to maximize therapeutic efficacy while minimizing systemic side effects.

  13. Frequency and function in the basal ganglia: the origins of beta and gamma band activity.

    Science.gov (United States)

    Blenkinsop, Alexander; Anderson, Sean; Gurney, Kevin

    2017-07-01

    Neuronal oscillations in the basal ganglia have been observed to correlate with behaviours, although the causal mechanisms and functional significance of these oscillations remain unknown. We present a novel computational model of the healthy basal ganglia, constrained by single unit recordings from non-human primates. When the model is run using inputs that might be expected during performance of a motor task, the network shows emergent phenomena: it functions as a selection mechanism and shows spectral properties that match those seen in vivo. Beta frequency oscillations are shown to require pallido-striatal feedback, and occur with behaviourally relevant cortical input. Gamma oscillations arise in the subthalamic-globus pallidus feedback loop, and occur during movement. The model provides a coherent framework for the study of spectral, temporal and functional analyses of the basal ganglia and lays the foundation for an integrated approach to study basal ganglia pathologies such as Parkinson's disease in silico. Neural oscillations in the basal ganglia (BG) are well studied yet remain poorly understood. Behavioural correlates of spectral activity are well described, yet a quantitative hypothesis linking time domain dynamics and spectral properties to BG function has been lacking. We show, for the first time, that a unified description is possible by interpreting previously ignored structure in data describing globus pallidus interna responses to cortical stimulation. These data were used to expose a pair of distinctive neuronal responses to the stimulation. This observation formed the basis for a new mathematical model of the BG, quantitatively fitted to the data, which describes the dynamics in the data, and is validated against other stimulus protocol experiments. A key new result is that when the model is run using inputs hypothesised to occur during the performance of a motor task, beta and gamma frequency oscillations emerge naturally during static-force and

  14. [Effects of recombinant human alpha-2b and gamma interferons on bone marrow megakaryocyte progenitors (CFU-Meg) from patients with chronic myelocytic leukemia].

    Science.gov (United States)

    Tanabe, Y; Dan, K; Kuriya, S; Nomura, T

    1989-10-01

    The effects of recombinant human interferon (IFN) alpha-2b and gamma on the bone marrow megakaryocyte progenitors (CFU-Meg) were compared between eight patients in the chronic phase of Ph1-positive chronic myelocytic leukemia (CML) and five hematologically normal patients. CFU-Meg was assayed in plasma clot culture added with phytohemagglutinin-stimulated leukocyte-conditioned medium as a source of colony stimulating activity. The average count of CFU-Meg colonies formed from the bone marrow of CML patients was 5.5 times that of normal controls. Spontaneous CFU-Meg colonies were grown in seven of eight CML patients, but in none of five controls. Colony formation by CFU-Meg in CML as well as normal bone marrow was suppressed by the two preparations of IFN in a dose dependent fashion. Their suppressive influence on colonies from CFU-Meg was comparable between CML and normal bone marrow at lower concentrations, but was less marked for CML than normal bone marrow at higher concentrations. The formation of CFU-Meg colonies from CML bone marrow was more severely suppressed by IFN-gamma than IFN-alpha-2b. Depletion of either T lymphocytes or adherent cells from the CML bone marrow cells diminished the suppressive effects of IFN-gamma, but had no influence on the effects of IFN-alpha-2b.

  15. Beta decay of the fission product 125Sb and a new complete evaluation of absolute gamma ray transition intensities

    Science.gov (United States)

    Rajput, M. U.; Ali, N.; Hussain, S.; Mujahid, S. A.; MacMahon, D.

    2012-04-01

    The radionuclide 125Sb is a long-lived fission product, which decays to 125Te by negative beta emission with a half-life of 1008 day. The beta decay is followed by the emission of several gamma radiations, ranging from low to medium energy, that can suitably be used for high-resolution detector calibrations, decay heat calculations and in many other applications. In this work, the beta decay of 125Sb has been studied in detail. The complete published experimental data of relative gamma ray intensities in the beta decay of the radionuclide 125Sb has been compiled. The consistency analysis was performed and discrepancies found at several gamma ray energies. Evaluation of the discrepant data was carried out using Normalized Residual and RAJEVAL methods. The decay scheme balance was carried out using beta branching ratios, internal conversion coefficients, populating and depopulating gamma transitions to 125Te levels. The work has resulted in the consistent conversion factor equal to 29.59(13) %, and determined a new evaluated set of the absolute gamma ray emission probabilities. The work has also shown 22.99% of the delayed intensity fraction as outgoing from the 58 d isomeric 144 keV energy level and 77.01% of the prompt intensity fraction reaching to the ground state from the other excited states. The results are discussed and compared with previous evaluations. The present work includes additional experimental data sets which were not included in the previous evaluations. A new set of recommended relative and absolute gamma ray emission probabilities is presented.

  16. Beta decay of the fission product 125Sb and a new complete evaluation of absolute gamma ray transition intensities

    International Nuclear Information System (INIS)

    Rajput, M.U.; Ali, N.; Hussain, S.; Mujahid, S.A.; MacMahon, D.

    2012-01-01

    The radionuclide 125 Sb is a long-lived fission product, which decays to 125 Te by negative beta emission with a half-life of 1008 day. The beta decay is followed by the emission of several gamma radiations, ranging from low to medium energy, that can suitably be used for high-resolution detector calibrations, decay heat calculations and in many other applications. In this work, the beta decay of 125 Sb has been studied in detail. The complete published experimental data of relative gamma ray intensities in the beta decay of the radionuclide 125 Sb has been compiled. The consistency analysis was performed and discrepancies found at several gamma ray energies. Evaluation of the discrepant data was carried out using Normalized Residual and RAJEVAL methods. The decay scheme balance was carried out using beta branching ratios, internal conversion coefficients, populating and depopulating gamma transitions to 125 Te levels. The work has resulted in the consistent conversion factor equal to 29.59(13) %, and determined a new evaluated set of the absolute gamma ray emission probabilities. The work has also shown 22.99% of the delayed intensity fraction as outgoing from the 58 d isomeric 144 keV energy level and 77.01% of the prompt intensity fraction reaching to the ground state from the other excited states. The results are discussed and compared with previous evaluations. The present work includes additional experimental data sets which were not included in the previous evaluations. A new set of recommended relative and absolute gamma ray emission probabilities is presented.

  17. Modulation of interferon-gamma-induced HLA-DR expression on the human keratinocyte cell line SCC-13 by ultraviolet radiation

    International Nuclear Information System (INIS)

    Khan, I.U.; Boehm, K.D.; Elmets, C.A.

    1993-01-01

    Cell surface expression of major histocompatibility determinants on epidermal keratinocytes is a characteristic feature of a number of inflammatory dermatoses and in all likelihood is caused by diffusion of human leukocyte antigen (HLA)-DR-inducing cytokines from cells present in the dermal mononuclear cell infiltrate. Many of these same disorders respond to ultraviolet (UV) radiation phototherapy. Using the human SCC-13 keratinocyte cell line as a model, UV radiation was found to inhibit interferon-gamma-induced HLA-DR expression. Inhibition correlated closely with decreased steady-state levels of HLA-DR mRNA. These findings provide evidence that the therapeutic effect of UV radiation phototherapy may be mediated by its capacity to down-regulate cytokine-induced keratinocyte HLA-DR expression. (Author)

  18. Tuberculosis screening of new hospital employees: compliance, clearance to work time, and cost using tuberculin skin test and interferon-gamma release assays.

    Science.gov (United States)

    Foster-Chang, Sarah A; Manning, Mary L; Chandler, Laura

    2014-11-01

    Selection of the most suitable test(s) for detection of Mycobacterium tuberculosis (TB) infection should be based on purpose, setting, effectiveness, and cost. Two tests are available to screen for latent TB: the tuberculin skin test (TST) and the more recent interferon-gamma release assays (IGRAs). Based on the administrative, logistic, and technical ease of use, an IGRA trial was initiated by the occupational health department at an urban Veteran's Administration health care facility for TB screening of new employees. As a result, new employees completing the pre-placement process within the organization's designated 14 days increased from 77% to 97%, new employee clearance to work time decreased from 13.18 to 5.91 days, and new employee TB screening costs were reduced by 40%. The IGRA is an acceptable alternative to the TST and has significant potential to improve the process of pre-placement TB screening. Copyright 2014, SLACK Incorporated.

  19. A gene duplication led to specialized gamma-aminobutyrate and beta-alanine aminotransferase in yeast

    DEFF Research Database (Denmark)

    Andersen, Gorm; Andersen, Birgit; Dobritzsch, D.

    2007-01-01

    and related yeasts have two different genes/enzymes to apparently 'distinguish' between the two reactions in a single cell. It is likely that upon duplication similar to 200 million years ago, a specialized Uga1p evolved into a 'novel' transaminase enzyme with broader substrate specificity.......In humans, beta-alanine (BAL) and the neurotransmitter gamma-aminobutyrate (GABA) are transaminated by a single aminotransferase enzyme. Apparently, yeast originally also had a single enzyme, but the corresponding gene was duplicated in the Saccharomyces kluyveri lineage. SkUGA1 encodes a homologue...... to characterize the substrate specificity and kinetic parameters of the four enzymes. It was found that the cofactor pyridoxal 5'-phosphate is needed for enzymatic activity and alpha-ketoglutarate, and not pyruvate, as the amino group acceptor. SkPyd4p preferentially uses BAL as the amino group donor (V...

  20. Assessment of gamma, beta and alpha-particle-emitting nuclides in marine samples

    International Nuclear Information System (INIS)

    Holm, E.

    1997-01-01

    Depending on the physical properties of radionuclides different systems must be used for their measurement. Most convenient is if gamma spectrometry can be used by germanium, Silicon or Scintillation detectors (eg. NaI). If, however, the main emission consists of beta or alpha particles or low-energy photons as is the case for radionuclides decaying by electron capture, radiochemical separation and specific source preparations must be undertaken. In such cases also the radiochemical yield must be determined. The radiochemical part mainly follows the lines presented by prof. T. Jaakkola, Department of Radiochemistry, Helsinki, Finland, at a course in radioecology in Lurid, 1991. For very long-lived radionuclides other methods such as mass spectrometry are superior although often associated with sophisticated expensive instrumentation. (author)

  1. An energy-independent dose rate meter for beta and gamma radiation

    International Nuclear Information System (INIS)

    Heinzelmann, M.; Keller, M.

    1986-01-01

    An easy to handle dose rate meter has been developed at the Juelich Nuclear Research Centre with a small probe for the energy-independent determination of the dose rate in mixed radiation fields. The dose rate meter contains a small ionisation chamber with a volume of 15.5 cm 3 . The window of the ionisation chamber consists of an aluminised plastic foil of 7 mg.cm -2 . The dose rate meter is suitable for determining the dose rate in skin. With a supplementary depth dose cap, the dose rate can be determined in tissue at a depth of 1 cm. The dose rate meter is energy-independent within +-20% for 147 Pm, 204 Tl and 90 Sr/ 90 Y beta radiation and for gamma radiation in the energy range above 35 keV. (author)

  2. Neutralizing antibodies explain the poor clinical response to Interferon beta in a small proportion of patients with Multiple Sclerosis: a retrospective study

    Directory of Open Access Journals (Sweden)

    Cefaro Luca

    2009-10-01

    Full Text Available Abstract Background Neutralizing antibodies (NAbs against Interferon beta (IFNβ are reported to be associated with poor clinical response to therapy in multiple sclerosis (MS patients. We aimed to quantify the contribution of NAbs to the sub-optimal response of IFNβ treatment. Methods We studied the prevalence of NAbs in MS patients grouped according to their clinical response to IFNβ during the treatment period. Patients were classified as: group A, developing ≥ 1 relapse after the first 6 months of therapy; group B, exhibiting confirmed disability progression after the first 6 months of therapy, with or without superimposed relapses; group C, presenting a stable disease course during therapy. A cytopathic effect assay tested the presence of NAbs in a cohort of ambulatory MS patients treated with one of the available IFNβ formulations for at least one year. NAbs positivity was defined as NAbs titre ≥ 20 TRU. Results Seventeen patients (12.1% were NAbs positive. NAbs positivity correlated with poorer clinical response (p Conclusion The majority of patients with poor clinical response are NAbs negative suggesting that NAbs explains only partially the sub-optimal response to IFNβ.

  3. A comparative study of melatonin and immunomodulatory therapy with interferon beta and glatiramer acetate in a mouse model of multiple sclerosis.

    Science.gov (United States)

    Ramos González, E J; Ramirez Jirano, L J; García Martínez, D Z; Ortiz, G G; Jave Suárez, L F; Leal Cortes, C A; Bitzer Quintero, O K

    2018-03-08

    Multiple sclerosis (MS) is a chronic, demyelinating, autoimmune disease of the central nervous system causing neuroinflammation. Experimental autoimmune encephalitis (EAE) is a model of the disease. MS is classically treated with interferon beta (IFN-β) and glatiramer acetate (GA). Melatonin (MLT) has been reported to modulate immune system responses. The aim of the present study is to analyse the effects of MLT administration in comparison with the first-line treatments for MS (IFN-β and GA). EAE was induced in male Sprague-Dawley rats; the animals subsequently received either IFN-β, GA, or MLT. Cerebrospinal fluid (CSF) samples were analysed by multiplex assay to determine the levels of proinflammatory cytokines. The neurological evaluation of EAE was also recorded. All immunised animals developed EAE. We evaluated the first relapse-remission cycle, observing that IFN-β and GA had better results than MLT in the clinical evaluation. Neither EAE nor any of the treatments administered modified CSF IL-1β and IL-12p70 concentrations. However, IFN-β and MLT did decrease CSF TNF-α concentrations. Further studies are needed to evaluate the molecular mechanisms involved in the behaviour of MLT in EAE, and to quantify other cytokines in different biological media in order for MLT to be considered an anti-inflammatory agent capable of regulating MS. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Development and Validation of an Enzyme-Linked Immunosorbent Assay for the Detection of Binding Anti-Drug Antibodies against Interferon Beta

    Directory of Open Access Journals (Sweden)

    Kathleen Ingenhoven

    2017-07-01

    Full Text Available ObjectiveTo develop and validate a method for the detection of binding anti-drug antibodies (ADAs against interferon beta (IFN-β in human serum as part of a European initiative (ABIRISK aimed at the prediction and analysis of clinical relevance of anti-biopharmaceutical immunization to minimize the risk.MethodA two-tiered bridging enzyme-linked immunosorbent assay (ELISA format was selected and validated according to current recommendations. Screening assay: ADA in serum samples form complexes with immobilized IFN-β and biotinylated IFN-β, which are then detected using HRP labeled Streptavidin and TMB substrate. Confirmation assay: Screen “putative positive” samples are tested in the presence of excess drug (preincubation of sera with 0.3 µg/mL of soluble IFN-β and percentage of inhibition is calculated.ResultsThe assay is precise, and the sensitivity of the assay was confirmed to be 26 ng/mL using commercially available polyclonal rabbit antihuman IFN-β in human sera as the positive control.ConclusionAn ultrasensitive ELISA for IFN-β-binding ADA testing has been validated. This will form the basis to assess anti-biopharmaceutical immunization toward IFN-β with regards to its clinical relevance and may allow for the development of predictive tools, key aims within the ABIRISK consortium.

  5. Cyclosporin A Inhibits Rotavirus Replication and Restores Interferon-Beta Signaling Pathway In Vitro and In Vivo

    Science.gov (United States)

    He, Haiyang; Wu, Yuzhang

    2013-01-01

    Rotavirus (RV) is the most common cause of severe diarrhea among infants and young children. Currently, there is no specific drug available against rotavirus, largely due to the lack of an ideal target molecule which has hampered drug development. Our previous studies have revealed that cyclosporin A (CsA) might be potentially useful as an anti-RV drug. We therefore used both cellular and mouse models to study the immunological safety and effectiveness of CsA as an anti-RV drug. We found that CsA treatment of HT-29 cells before, during, and after viral infection efficiently inhibited Wa strain RV replication and restored IFN-β expression in a HT-29 cell line model. Exploring the underlying mechanisms showed that CsA promoted Interferon Regulatory Factor-5 (IRF-5) expression (a key positive regulator of the type I IFN signaling pathway), but not IRF-1, IRF-3, or IRF-7. Additionally, CsA inhibited SOCS-1 expression (the key negative regulator of IFN-α/β), but not SOCS-2 or SOCS-3. The antiviral effect of CsA was confirmed in an RV-infected neonatal mouse model by evaluation of antigen clearance and assessment of changes in intestinal tissue pathology. Also, no differences in T cell frequency or proliferation between the CsA- and vehicle-treated groups were observed. Thus, both our in vitro and in vivo findings suggest that CsA, through modulating the expression of key regulators in IFN signaling pathway, promote type I IFN-based intracellular innate immunity in RV host cells. These findings suggest that CsA may be a useful candidate to develop a new anti-RV strategy, although further evaluation and characterization of CsA on RV-induced diarrhea are warranted. PMID:23990993

  6. Differential expression of gamma-tubulin and class III beta-tubulin in medulloblastomas and human medulloblastoma cell lines

    Czech Academy of Sciences Publication Activity Database

    Caracciolo, V.; D´Agostino, L.; Dráberová, Eduarda; Sládková, Vladimíra; Crozier-Fitzgerald, C.; Agamanolis, D.P.; De Chadarévian, J.P.; Legido, A.; Giordano, A.; Dráber, Pavel; Katsetos, C.D.

    2010-01-01

    Roč. 223, č. 2 (2010), s. 519-529 ISSN 0021-9541 R&D Projects: GA AV ČR KAN200520701 Institutional research plan: CEZ:AV0Z50520514 Keywords : gamma-tubulin * beta III-tubulin * meduloblastoma Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.986, year: 2010

  7. An easy and efficient method to produce {gamma}-amino alcohols by reduction of {beta}-enamino ketones

    Energy Technology Data Exchange (ETDEWEB)

    Harris, Maria Ines N.C.; Braga, Antonio C.H. [Universidade Estadual de Campinas, SP (Brazil). Inst. de Quimica]. E-mail: herrera@iqm.unicamp.br

    2004-12-01

    Reduction of {beta}-enamino ketones 2 with NaBH{sub 4} in glacial acetic acid gave {gamma}-amino alcohols 1 in 70% to 98% yield with diastereomeric excesses, preferentially the syn product, from 44% to 90%. The stereochemistry of these compounds was confirmed by analysis of their tetrahydro-1,3-oxazine derivatives 3. (author)

  8. Peculiarities of the clinical course of radiation sickness and organizational decisions for radiation accidents with beta-gamma sources

    International Nuclear Information System (INIS)

    Guskova, A.K.; Gusev, I.A.

    1998-01-01

    The analysis of a number of recent large scale accidents involving beta-gamma sources in the last 40 years, such as those of the Marshall Islands (1954); Windscale, UK (1957); Chernobyl, USSR (1986) and Goiania, Brazil (1987) demonstrates the predominance and importance of health and social impacts. (author)

  9. Effect of water on self-assembled tubules in {beta}-sitosterol + {gamma}-oryzanol-based organogels

    Energy Technology Data Exchange (ETDEWEB)

    Adel, Ruud den; Heussen, Patricia C M; Bot, Arjen, E-mail: ruud-den.adel@unilever.co [Unilever Research and Development Vlaardingen, Olivier van Noortlaan 120, NL-3133 AT Vlaardingen (Netherlands)

    2010-10-01

    Mixtures of {beta}-sitosterol and {gamma}-oryzanol form a network in triglyceride oil that may serve as an alternative to the network of small crystallites of triglycerides occurring in regular oil structuring. The present x-ray diffraction study investigates the relation between the crystal forms of the individual compounds and the mixture in oil, water and emulsion. {beta}-Sitosterol and {gamma}-oryzanol form normal crystals in oil, in water, or in emulsions. The crystals are sensitive to the presence of water. The mixture of {beta}-sitosterol + {gamma}-oryzanol forms crystals in water and emulsions that can be traced back to the crystals of the pure compounds. Only in oil, a completely different structure emerges in the mixture of {beta}-sitosterol + {gamma}-oryzanol, which bears no relation to the structures that are formed by both individual compounds, and which can be identified as a self-assembled tubule (diameter 7.2{+-}0.1 nm, wall thickness 0.8{+-}0.2 nm).

  10. Decontamination Experiments on Intact Pig Skin Contaminated with Beta-Gamma- Emitting Nuclides

    Energy Technology Data Exchange (ETDEWEB)

    Edvardsson, K A; Hagsgaard, S [AB Atomenergi, Nykoeping (Sweden); Swensson, A [Dept. of Occupational Medicine, Karolinska Sjukhuset, Stockholm (Sweden)

    1966-11-15

    A number of decontamination experiments have been performed on intact pig skin. In most of the experiments NaI-131 in water solution has been utilized because this nuclide is widely used within the Studsvik research establishment, is easy to detect and relatively harmless, and is practical to use in these experiments. Among the {beta} {gamma}-nuclides studied 1-131 has furthermore proved to be the one most difficult to remove from the skin. The following conclusions and recommendations regarding the decontamination of skin are therefore valid primarily for iodine in the form of Nal, but are probably also applicable to many other {beta} {gamma}-nuclides. a) A prolonged interval between contamination and decontamination has a negative effect on the result of the decontamination. Therefore start decontamination as soon as possible after the contamination. b) Soap and water has proved to be the most suitable decontamination agent. A number of other agents have appeared to be harmful to the skin. Therefore, first of all use only soap and water in connection with gentle rubbing. c) No clear connection between the temperature of the water for washing and the result of the decontamination has been demonstrated. d) Skin not degreased before the contamination seems to be somewhat easier to decontaminate than degreased skin, particularly if the activity has been on the skin for a long time. Therefore do not remove the sebum of the skin when engaged on radioactive work involving contamination risks. e) Irrigation of the contaminated surface with a solution containing the corresponding inactive ions or ordinary water in large quantities may considerably decrease the skin contamination. f) In radioactive work of long duration involving high risks of contamination prophylactic measures in the form of a protective substance ('invisible glove'), type Kerodex, may make decontamination easier.

  11. An Optimized Design of Single-Channel Beta-Gamma Coincidence Phoswich Detector by Geant4 Monte Carlo Simulations

    Directory of Open Access Journals (Sweden)

    Weihua Zhang

    2011-01-01

    Full Text Available An optimized single-channel phoswich well detector design has been proposed and assessed in order to improve beta-gamma coincidence measurement sensitivity of xenon radioisotopes. This newly designed phoswich well detector consists of a plastic beta counting cell (BC404 embedded in a CsI(Tl crystal coupled to a photomultiplier tube. The BC404 is configured in a cylindrical pipe shape to minimise light collection deterioration. The CsI(Tl crystal consists of a rectangular part and a semicylindrical scintillation part as a light reflector to increase light gathering. Compared with a PhosWatch detector, the final optimized detector geometry showed 15% improvement in the energy resolution of a 131mXe 129.4 keV conversion electron peak. The predicted beta-gamma coincidence efficiencies of xenon radioisotopes have also been improved accordingly.

  12. Line C17: alpha and medium-level beta-gamma laboratory pilot facility

    International Nuclear Information System (INIS)

    Calor, J.N.; Mauborgne, B.; Montuir, M.

    2000-01-01

    The Process Development Laboratory (LDP) uses the ATALANTE C17 line for integral testing in order to develop and validate spent fuel reprocessing methods and for overall qualification of calculation codes. Line C 17 comprises shielded cells and glove boxes, equipped with centrifugal extractors and laboratory-scale mixer-settlers to test liquid-liquid extraction processes in an alpha and medium-level beta-gamma environment. The high reliability and precision of the process instrumentation and control system allow full control of operating parameters and comprehensive operating data recording, meeting the experimentation quality requirements necessary for qualifying calculation codes. Direct online spectrophotometric analysis at various points in the process provides real-time concentration data for vital elements, some of which are difficult to analyze offline because of their poor chemical stability. Online analyses, supplemented when necessary by gamma spectrometry, provide valuable process control input for reaching stabilized operating conditions. Fifteen radioactive test campaigns have been successfully completed since line C 17 was commissioned in June 1995. (authors)

  13. Influence of apolipoprotein E plasma levels and tobacco smoking on the induction of neutralising antibodies to interferon-beta

    DEFF Research Database (Denmark)

    Sena, Armando; Bendtzen, Klaus; Cascais, Maria J

    2010-01-01

    for apoE, smoking habit became associated with NAb induction: OR 5.6 (95% CI 1.3-87), P = 0.03. These results suggest that apoE-containing lipoprotein metabolism and, possibly, tobacco smoking may be associated with risk of NAb production in female MS patients treated with IFN-beta.......-negative, 83 (68-107) mg/L, P = 0.03, and 76 (66-87) mg/L, P = 0.04, respectively. When adjusting for age and smoking for a one-standard deviation decrease in apoE levels, a 5.6-fold increase in the odds of becoming NAb-positive was detected: odds ratios (OR) 0.18 (95% CI 0.04-0.77), P = 0.04. When adjusting...

  14. Effect of gamma radiation on the content {beta}-carotene and volatile compounds of cantaloupe melon

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Stefania P. de; Cardozo, Monique; Lima, Keila dos S.C.; Lima, Antonio L. dos S., E-mail: keila@ime.eb.br, E-mail: santoslima@ime.eb.br [Departamento de Quimica - IME - Instituto Militar de Engenharia, RJ (Brazil)

    2011-07-01

    The Japanese melon or cantaloupe (Cucumis melo L.) is characterized by fruits with almost 1.0 Kg, pulp usually salmon and musky scent. The fruits when ripe are sensitive to post harvest handling. This low transport resistance and reduced shelf-life makes it necessary to delay the ripening of fruit. In this way the use of irradiation technique is a good choice. Irradiation is the process of exposing food to high doses of gamma rays. The processing of fruits and vegetables with ionizing radiation has as main purpose to ensure its preservation. However, like other forms of food processing, irradiation may cause changes in chemical composition and nutritional value. This study aims to assess possible changes in carotene content and volatile compounds caused by exposure of cantaloupe melon fruit to gamma irradiation. Irradiation of the samples occurred in Centro Tecnologico do Exercito (Guaratiba-RJ), using Gamma irradiator (Cs{sub 137} source, dose rate 1.8 kGy/h), being applied 0.5 and 1.0 kGy doses and separated a control group not irradiated. Carotenoids were extracted with acetone and then suffered partition to petroleum ether, solvent was removed under nitrogen flow and the remainder dissolved in acetone again. The chromatographic analysis was performed using a Shimadzu gas chromatograph, with C30 column. For volatile compounds, we used gas chromatography (GC) associated with mass (MS). As a result, it was verified in analysis of carotenoids that cantaloupe melon is rich in {beta}-carotene. Both total content of carotenoids and specific {beta}-carotene amount wasn't suffer significant reduction in irradiated fruits at two doses, demonstrating that the irradiation process under these conditions implies a small loss of nutrients. The major volatile compounds were: 2-methyl-1-butyl acetate, ethyl hexanoate, n-hexyl acetate, benzyl acetate, 6-nonenyl acetate and {alpha} -terpinyl acetate. For all compounds we observed an increase in the volatile content in 0.5 k

  15. Interferon Gamma and PSA-Restricted Expression of FAS Ligand: A Novel Gene Therapy Strategy for Prostate Cancer

    National Research Council Canada - National Science Library

    Hall, Simon

    2003-01-01

    Introduction: Preliminary studies pointed to the ability for IFN-gamma to enhance sensitivity and/or reverse resistance to Fas transactivation on prostate cancer cells and work during the past 2 years illustrated...

  16. Evaluation of accuracy and uncertainty of ELISA assays for the determination of interleukin-4, interleukin-5, interferon-gamma and tumor necrosis factor-alpha

    DEFF Research Database (Denmark)

    Borg, Lone; Kristiansen, Jesper; Christensen, Jytte M

    2002-01-01

    . However, models for establishing the traceability and uncertainty of immunoassay results are lacking. Sandwich enzyme-linked immunosorbent assays (ELISAs) were developed for determination of the human cytokines interleukin-4 (IL-4), interleukin-5 (IL-5), interferon-y (IFN-gamma) and tumor necrosis factor-alpha...... (TNF-alpha). The accuracy of each of the assays was evaluated in the ranges of 1-15 microg/l (IL-4), 0.001-1 microg/l (IL-5), 0.5-2.5 microg/l (IFN-T) and 0.14-2.2 microg/l (TNF-alpha). Other evaluated performance characteristics were the limit of detection (LOD), immunological specificity......) of the assessed ELISAs was found to be in the range of 11-18%, except for IL-5 where RSDA increased at decreasing concentrations. The LOD was 0.12 microg/l, 0.0077 microg/l, 0.0069 microg/l and 0.0063 microg/l for IL-4, IL-5, IFN-gamma and TNF-alpha, respectively. Traceability to the WHO IS was established...

  17. Spectral shapes and a beta-gamma directional correlation in the beta decay of 172Tm (Jpi = 2-)

    DEFF Research Database (Denmark)

    Gregers Hansen, P.; Loft Nielsen, H.; Wilsky, K.

    1966-01-01

    The isotope 172Tm populates the 0+, 2+ and 4+ states of the 172Yb ground-state rotational band directly in beta decay. The shapes and intensities of the three beta groups have been measured by means of a six-gap magnetic spectrometer operated in coincidence with a Nal(Tl) crystal. The experimenta...

  18. The p110beta isoform of phosphoinositide 3-kinase signals downstream of G protein-coupled receptors and is functionally redundant with p110gamma.

    Science.gov (United States)

    Guillermet-Guibert, Julie; Bjorklof, Katja; Salpekar, Ashreena; Gonella, Cristiano; Ramadani, Faruk; Bilancio, Antonio; Meek, Stephen; Smith, Andrew J H; Okkenhaug, Klaus; Vanhaesebroeck, Bart

    2008-06-17

    The p110 isoforms of phosphoinositide 3-kinase (PI3K) are acutely regulated by extracellular stimuli. The class IA PI3K catalytic subunits (p110alpha, p110beta, and p110delta) occur in complex with a Src homology 2 (SH2) domain-containing p85 regulatory subunit, which has been shown to link p110alpha and p110delta to Tyr kinase signaling pathways. The p84/p101 regulatory subunits of the p110gamma class IB PI3K lack SH2 domains and instead couple p110gamma to G protein-coupled receptors (GPCRs). Here, we show, using small-molecule inhibitors with selectivity for p110beta and cells derived from a p110beta-deficient mouse line, that p110beta is not a major effector of Tyr kinase signaling but couples to GPCRs. In macrophages, both p110beta and p110gamma contributed to Akt activation induced by the GPCR agonist complement 5a, but not by the Tyr kinase ligand colony-stimulating factor-1. In fibroblasts, which express p110beta but not p110gamma, p110beta mediated Akt activation by the GPCR ligands stromal cell-derived factor, sphingosine-1-phosphate, and lysophosphatidic acid but not by the Tyr kinase ligands PDGF, insulin, and insulin-like growth factor 1. Introduction of p110gamma in these cells reduced the contribution of p110beta to GPCR signaling. Taken together, these data show that p110beta and p110gamma can couple redundantly to the same GPCR agonists. p110beta, which shows a much broader tissue distribution than the leukocyte-restricted p110gamma, could thus provide a conduit for GPCR-linked PI3K signaling in the many cell types where p110gamma expression is low or absent.

  19. Scintillation response of CsI: Tl crystal under neutron, gamma, alpha particles and beta excitations

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Maria da Conceicao Costa; Madi Filho, Tufic; Lopes, Valdir Maciel; Berretta, Jose Roberto; Cardenas, Jose Patricio Nahuel, E-mail: macoper@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2015-07-01

    Among the converters of X and gamma radiation in light photons, known as scintillators, the one which is the most efficient emits photons with a wavelength near 400 nm. Particularly, among them, the cesium iodine doped with thallium (CsI:Tl) crystal is that which matches better between the light emission spectrum (peak at 540 nm) and the quantum sensitivity curve of the photodiodes and CCD (Charge Coupled Device). This explains the renewed interest in using this crystal as scintillator. Although the CsI:Tl crystal is commercially available, its local development would give the possibility to obtain it in different geometric configurations and coupling. Moreover, there is a special interest in studying new conditions that will alter the properties of this crystal in order to achieve a optimal level of its functional characteristics. Having an efficient national scintillator with low cost is a strategic opportunity to study the response of a detector applied to different types of radiation. The crystal of cesium iodide activated with thallium (CsI:Tl) has a high gamma detection efficiency per unit volume. In this paper, the CsI:Tl crystal, grown by the vertical Bridgman technique in evacuated silica ampoules and with the purpose of use as radiation detectors, is described. To evaluate the scintillator, measures of the thallium distribution in the crystal volume were taken, with overall efficiency score. The scintillator response was studied through gamma radiation from sources of {sup 137}Cs, {sup 60}Co, {sup 22}Na, {sup 54}Mn, {sup 131}I and {sup 99m}Tc; the beta radiation from source of {sup 90}Sr/{sup 90}Y, alpha particles from {sup 241}Am source and the scintillator response to neutrons from Am/Be source. The energetic resolution for {sup 137}Cs gamma rays (662 keV) was 10%. The results showed the validity of using the CsI:Tl crystal developed in our laboratory, in many applications in the area of radiation detectors. (author)

  20. In vitro activated CD4+ T cells from interferon-gamma (IFN-gamma)-deficient mice induce intestinal inflammation in immunodeficient hosts

    DEFF Research Database (Denmark)

    Bregenholt, S; Brimnes, J; Nissen, Mogens Holst

    1999-01-01

    To investigate the role of IFN-gamma in the immunopathogenesis of inflammatory bowel disease (IBD), severe combined immunodeficient (SCID) mice were transplanted with in vitro activated CD4+ T cells from either wild-type (WT) or IFN-gamma-deficient (IFN-gammaKO) BALB/c mice. In vitro, the two types...... of T cells displayed comparable proliferation rates and production of tumour necrosis factor-alpha (TNF-alpha), IL-2, IL-4 and IL-10 after concanavalin A (Con A) stimulation. When transplanted into SCID mice, WT CD4+ blasts induced a lethal IBD, whereas IFN-gammaKO blasts induced a less severe...... intestinal inflammation with moderate weight loss. Intracellular cytokine staining of lamina propria lymphocytes (LPL) revealed comparable fractions of CD4+ T cells positive for TNF-alpha, IL-2 and IL-10 in the two groups of transplanted SCID mice, whereas a two-to-three-fold increase in the fraction of IL-4...

  1. Interferon-γ Inhibits Ebola Virus Infection.

    Directory of Open Access Journals (Sweden)

    Bethany A Rhein

    Full Text Available Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.

  2. Interferon-γ Inhibits Ebola Virus Infection.

    Science.gov (United States)

    Rhein, Bethany A; Powers, Linda S; Rogers, Kai; Anantpadma, Manu; Singh, Brajesh K; Sakurai, Yasuteru; Bair, Thomas; Miller-Hunt, Catherine; Sinn, Patrick; Davey, Robert A; Monick, Martha M; Maury, Wendy

    2015-01-01

    Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.

  3. A novel mechanism of skin tumor promotion involving interferon-gamma (IFNγ)/signal transducer and activator of transcription-1 (Stat1) signaling.

    Science.gov (United States)

    Bozeman, Ronald; Abel, Erika L; Macias, Everardo; Cheng, Tianyi; Beltran, Linda; DiGiovanni, John

    2015-08-01

    The current study was designed to explore the role of signal transducer and activator of transcription 1 (Stat1) during tumor promotion using the mouse skin multistage carcinogenesis model. Topical treatment with both 12-O-tetradecanoylphorbol-13-acetate (TPA) and 3-methyl-1,8-dihydroxy-9-anthrone (chrysarobin or CHRY) led to rapid phosphorylation of Stat1 on both tyrosine (Y701) and serine (S727) residues in epidermis. CHRY treatment also led to upregulation of unphosphorylated Stat1 (uStat1) at later time points. CHRY treatment also led to upregulation of interferon regulatory factor 1 (IRF-1) mRNA and protein, which was dependent on Stat1. Further analyses demonstrated that topical treatment with CHRY but not TPA upregulated interferon-gamma (IFNγ) mRNA in the epidermis and that the induction of both IRF-1 and uStat1 was dependent on IFNγ signaling. Stat1 deficient (Stat1(-/-) ) mice were highly resistant to skin tumor promotion by CHRY. In contrast, the tumor response (in terms of both papillomas and squamous cell carcinomas) was similar in Stat1(-/-) mice and wild-type littermates with TPA as the promoter. Maximal induction of both cyclooxygenase-2 and inducible nitric oxide synthase in epidermis following treatment with CHRY was also dependent on the presence of functional Stat1. These studies define a novel mechanism associated with skin tumor promotion by the anthrone class of tumor promoters involving upregulation of IFNγ signaling in the epidermis and downstream signaling through activated (phosphorylated) Stat1, IRF-1 and uStat1. © 2014 Wiley Periodicals, Inc.

  4. [Cost-effectiveness analysis of interferon beta-1b as treatment for patients with clinically isolated syndrome suggestive of multiple sclerosis in Spain].

    Science.gov (United States)

    Piñol, C

    2016-05-01

    The BENEFIT study has demonstrated the benefits of early treatment with interferon beta 1b (IFNβ-1b). The objective of this study was to estimate the efficiency of early vs delayed IFNβ-1b treatment in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) in Spain. A Markov model reflecting the social perspective was developed with time horizons ranging from 2 years to lifetime. A cohort of 1000 patients with CIS, whose health status had been measured on the Expanded Disability Symptom Scale (EDSS), included patients who received early IFNβ-1b treatment and those who did not. Data from the BENEFIT study were used to model EDSS progression and transitions to MS. Costs were estimated from published literature. Patient utilities were derived from EQ-5D data and published data. Mortality was estimated using life tables and EDSS data. Costs (€ at 2013 rates) and outcomes were discounted at 3% per annum. A probabilistic sensitivity analysis was performed. In the base case, both the incremental cost utility ratio (ICUR) and the incremental cost effectiveness ratio (ICER) of IFNβ-1b versus no treatment were dominant (more effective and less costly) from a social perspective. From the perspective of the Spanish Health System, the ICUR was € 40,702/QALY and the ICER was € 13/relapse avoided. Early treatment with IFNβ-1b after a CIS versus delayed treatment is efficient from a social perspective, but it may not be efficient from the perspective of the NHS which does not take non health-related costs into account. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  5. Characteristics of MR imaging of brain stem glioma for the treatment of combination chemotherapy with interferon-. beta. and ACNU in addition to radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Wakabayashi, Toshihiko; Yoshida, Jun; Sugita, Kenichiro (Nagoya Univ. (Japan). Faculty of Medicine)

    1990-08-01

    In an attempt to improve the prognosis of brain stem glioma patients, a new treatment using a combination of chemotherapy of interferon-{beta}, ACNU, (1) - (4 - Amino - 2 - methyl - 5 - primidinyl) - methyl - 3 - (2-chloroethyl) - 3 -nitrosourea hydrochloride, and radiation, so called IAR therapy, was utilized on 19 patients who were diagnosed through CT and/or MRI findings as having pontine glioma. Eight of these patients were given IAR therapy at four week intervals and the changes were checked on MRI. The MRI response was classified into 3 types, that is, type 1: diffuse low intensity lesion on T{sub 1} WI changing to isodensity and tumor mass disappearing rapidly; type 2: located high intensity lesion in low intensity on T{sub 1} WI once appearing on decreasing the whole tumor size, then this lesion disappearing gradually; type 3: spotted low and/or iso mosaic intensity lesion appearing on and after treatment, with little change in tumor mass. The type 1 patients showed rapid improvement of neurological deficits and good recovery was obtained. Type 2 patients also recovered well but at recurrent periods tended to show disseminated sings intraspinally. The type 3 patients did not recover from neurological deficits well. But there were no significant differences of prognosis among these 3 types. Furthermore, MRI showed more precise data than CT scan on brain stem lesions and seemed to be more useful for diagnosis and follow-up treatment than CT scan. Though it is suggested that IAR combination therapy should be respected as the first choice for the treatment of brain stem glioma, it is strongly requested that some maintenance therapy is established for continuing the reduction time after induction of complete or partial remission with IAR therapy. (author).

  6. Calibrated radioactive sources - absolute measurements using a 4{pi} {beta}-{gamma} apparatus; Sources etalons de radioactivite - mesures absolues au moyen d'un ensemble 4{pi} {beta}-{gamma}

    Energy Technology Data Exchange (ETDEWEB)

    Benoit, P; Philis, C [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1965-07-01

    In this paper, the principle of the standardization of the radioisotopes by the 4{pi} {beta} - {gamma} coincidence method is reminded. Some theoretical examples are given emphasizing on instrumental coincidences and their corrections. The experimental apparatus is described: one discusses the choice of the experimental conditions for the many isotopes measured. Results are given and discussed. In appendix we describe the preparation of the sources. (authors) [French] Dans ce rapport, nous rappelons d'abord le principe de la methode d'etalonnage 4{pi} {beta} - {gamma} en donnant quelques exemples theoriques et en insistant sur la correction des erreurs instrumentales. Une description critique de l'appareillage utilise est donnee. On discute le choix des conditions experimentales pour divers isotopes mesures et les resultats obtenus. En annexe, nous decrivons la fabrication des sources que nous mesurons.

  7. Simultaneos determination of absorbed doses due to beta and gamma radiations with CaSO4: Dy produced at Ipen

    International Nuclear Information System (INIS)

    Campos, L.L.; Rosa, L.A.R. da.

    1988-07-01

    Due to the Goiania radiological accident, it was necessary to develop urgently a dosimeter in order to evaluate, simultaneously, beta and gamma absorbed doses, due to 137 Cs radiations. Therefore, the Dosimetric Material Production Laboratory of IPEN developed a simple, practical, light and low cost badge using small thickness (0,20mm) thermoluminescent CaSO 4 : Dy pellets produced by the same laboratory. This pellets are adequate for beta radiation detection. These dosimeters were worn by some IPEN technicians who worked in Goiania city, and were used to evaluate the external and internal contaminations presented by the accident victims interned at the Hospital Naval Marcilio Dias. (author) [pt

  8. Ultraviolet observations of. beta. Persei,. mu. /sup 1/ Scorpii and. gamma. /sub 2/ Velorum with the TD-1A satellite

    Energy Technology Data Exchange (ETDEWEB)

    Sahade, J [Instituto de Astronomia y Fisica del Espacio, Buenos Aires (Argentina); van der Hucht, K A [Laboratorium voor Ruimteonderzoek, Utrecht (Netherlands). Space Research Lab.

    1980-05-01

    This paper reports on the results of a study of S59 ultraviolet spectral scans of the spectroscopic binaries ..beta.. Persei, ..mu../sup 1/ Scorpii and ..gamma../sub 2/ Velorum. In the case of ..mu../sup 1/ Sco it was found that the Mg II doublet at 2800 Angstroem undergoes intensity variations that may be indicative of variable emission in the photographic spectrum. The continuum in the 2490-2590 Angstroem range deviates from the continuum of the 'comparison stars'. In ..gamma../sub 2/ Vel, flux variations in the 2770-2870 A region have been detected.

  9. Radioprotective effect of interferon

    Energy Technology Data Exchange (ETDEWEB)

    Zasukhina, G.

    1984-12-18

    A cycle of experiments performed jointly with associations of the Moscow Engineering Physics Institute reportedly demonstrated that interferons protect human cells cultivated in a test tube against the action of fast neutrons and gamma radiation. Cells treated in advance with interferon not only survived irradiation but were almost totally protected against harmful effects of fast neutrons on the structure of chromosomes, according to the author. She mentions that the laboratory has also been studying effects produced on cells by compounds of heavy metals and other chemical compounds, including ones which cause breaks in the DNA molecule. Interferon's ability to protect cells against effects of chemical compounds has been studied in this connection. Another direction of the laboratory's work is research on interferon's effects on blood cells of persons suffering from certain hereditary diseases in which restorative processes of cells are impaired. The purpose of this is to develop courses of treatment which will not cause irreversible damages to chromosomes, the author explains. Interferon has been found to stimulate the reparation systems of cells in cases of Marfan's syndrome, for example.

  10. No changes in serum concentrations of interleukin 10 (IL-10) and interferon gamma (IF-gamma) before and after treatment of the thyroid eye disease (TED).

    Science.gov (United States)

    Laban-Guceva, Nevenka; Antova, Magdalena; Bogoev, Milco

    2007-11-01

    TED is a severe eye disease leading in rare cases to decrease of sight, optic nerve compression and blindness. Recently, significant progresses in understanding the disease have been done. Nevertheless, the treatment of the disease, especially in its severe form remains challenging. Glucocorticoids (GC) have been the basis of the treatment for a long time. Orbital irradiation (OI) and optical decompression (OD) are also used in managing the severe forms of TED. Somatostatin, intravenous immunoglobulin have been also used, with conflicting results. Regarding the potential for the treatment of TED with cytokine antagonists, controlled clinical studies are not available. Since cytokines play an important role in the pathogenesis of the TED, they seemed to be logical choice for modern TED treatment. It has been shown that both Th1 (interleukin-2, tumor necrosis factor gamma, interleukin gamma) and Th2 (interleukin -4, -5, -10) profile T cells are activated in the TED. We therefore measured interleukin-gamma, IF-gamma and interleukin -10 (IL-10)(Th1 and Th2 pattern) to assess its relationship to the course of the disease. This paper shows that both Th1 (IL-2) and Th2 (IF-gamma) pathways represented by those two cytokines are not involved (IL-10 before 2.29+/-5.23 and after treatment 3.77+/-8.44; IF gamma before 0.50+/-0.24 and after treatment 0.35+/-0.19). No relationship to the response to treatment was found. GC resulted in positive response in 8/22 patients, OI (12 patients) given after CS therapy, resulted in a response in all patients. Increase in proptosis, loss of visual acuity is spite of CS treatment prompted OD in two patients, who both recovered visual acuity and proptosis fell under 25 mm Hertel.

  11. Gamma-spectrometric and total alpha-beta counting methods for radioactivity analysis of deuterium depleted water

    International Nuclear Information System (INIS)

    Ferdes, Ov. S.; Mladin, C.; Vladu, Mihaela; Bulubasa, G.; Bidica, N.

    2008-01-01

    According to national regulations, as well as to the EU directive on the quality of drinking water, the radionuclide concentrations represent some of the drinking water quality parameters. Among the most important radioactivity content parameters are: the total alpha and total beta concentration (Bq/l); K-40 content, and the gamma-nuclides volume activities. The paper presents the measuring methods for low-level total alpha and/or beta counting of volume samples, as well as the high-resolution gamma-ray spectrometric method used to measure the volume activity of nuclides in drinking water. These methods are applied to monitor the radioactivity content and quality of the QLARIVIA brand of Deuterium depleted water (DDW). There are discussed the performances of these applied methods as well as some preliminary results. (authors)

  12. Latent transforming growth factor beta1 activation in situ: quantitative and functional evidence after low-dose gamma-irradiation

    Science.gov (United States)

    Ehrhart, E. J.; Segarini, P.; Tsang, M. L.; Carroll, A. G.; Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

    1997-01-01

    The biological activity of transforming growth factor beta1 (TGF-beta) is controlled by its secretion as a latent complex in which it is noncovalently associated with latency-associated peptide (LAP). Activation is the extracellular process in which TGF-beta is released from LAP, and is considered to be a primary regulatory control. We recently reported rapid and persistent changes in TGF-beta immunoreactivity in conjunction with extracellular matrix remodeling in gamma-irradiated mouse mammary gland. Our hypothesis is that these specific changes in immunoreactivity are indicative of latent TGF-beta activation. In the present study, we determined the radiation dose response and tested whether a functional relationship exists between radiation-induced TGF-beta and collagen type III remodeling. After radiation exposures as low as 0.1 Gy, we detected increased TGF-beta immunoreactivity in the mammary epithelium concomitant with decreased LAP immunostaining, which are events consistent with activation. Quantitative image analysis demonstrated a significant (P=0.0005) response at 0.1 Gy without an apparent threshold and a linear dose response to 5 Gy. However, in the adipose stroma, loss of LAP demonstrated a qualitative threshold at 0.5 Gy. Loss of LAP paralleled induction of collagen III immunoreactivity in this tissue compartment. We tested whether TGF-beta mediates collagen III expression by treating animals with TGF-beta panspecific monoclonal antibody, 1D11.16, administered i.p. shortly before irradiation. Radiation-induced collagen III staining in the adipose stroma was blocked in an antibody dose-dependent manner, which persisted through 7 days postirradiation. RNase protection assay revealed that radiation-induced elevation of total gland collagen III mRNA was also blocked by neutralizing antibody treatment. These data provide functional confirmation of the hypothesis that radiation exposure leads to latent TGF-beta activation, support our interpretation of the

  13. Characterization of commercial proton exchange membrane materials after exposure to beta and gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Thomson, S.N.; Carson, R.; Muirhead, C.; Li, H.; Castillo, I.; Boniface, H.; Suppiah, S. [Canadian Nuclear Laboratories, Chalk River, ON (Canada); Ratnayake, A.; Robinson, J. [Tyne Engineering Inc., Burlington, ON (Canada)

    2015-03-15

    Proton Exchange Membrane (PEM) type electrolysis cells have a potential use for tritium removal and heavy water upgrading. AECL is currently exposing various commercial PEM materials to both gamma (Cobalt-60 source) and beta (tritiated water) radiation to study the effects of radiation on these materials. This paper summarizes the testing methods and results that have been collected to date. The PEM materials that are or have been exposed to radiation are: Nafion 112, 212, 117 and 1110. Membrane characterization pre- and post- exposure consists of non-destructive inspection (FTIR, SEM/XPS), mechanical (tensile strength, percentage elongation, and modulus), electrical (resistance), or chemical (ion-exchange capacity - IEC). It has appeared that the best characterization techniques to compare exposed versus unexposed membranes were IEC, ultimate tensile strength and percent elongation. These testing techniques are easy and cheap to perform. The non-destructive tests, such as SEM and FTIR did not provide particularly useful information on radiation-induced degradation. Where changes in material properties were measured after radiation exposure, they would be expected to result in poorer cell performance. However, for modest γ-radiation exposure, all membranes showed a slight decrease in cell voltage (better performance). In contrast, the one β-radiation exposed membrane did show the expected increase in cell voltage. The counterintuitive trend for γ-radiation exposed membranes is not yet understood. Based on these preliminary results, it appears that γ- and β-radiation exposures have different effects.

  14. A new approach to beta-gamma coincidence counting. Advance report on the Samar electronic system

    International Nuclear Information System (INIS)

    Carlos, J. E. de; Granados, C. E.

    1972-01-01

    In 4π β-γ coincidence measurements, precision on the evaluation of coincidence counting losses is made difficult because of complex overlapping effects between theβ--and γ-side dead times due to pre cursive counted events. In this context the SAMAR electronic system is aimed to give a precise way of automatic counting and reduce the need for calculated corrections. This report describes its configuration and basic features. The SAMAR has been conceived in such a manner that both beta and gamma chains are sharing a common and non extending dead-time which is simultaneously applied to both channels. The shared dead time is made to be the only one inserted throughout the chains. Overlapping effects vanish and the three counting channels have identical transmission ratios. A new dead-time circuit based on fast linear gates as blocking elements has been developed. Application of the two-oscillator Muller's method evidences a fully non-extending character. Automatism is implemented by using a live timer corrective channel controlling the counting scalers. (Author) 21 refs

  15. Management of defense beta-gamma contaminated solid low-level wastes

    International Nuclear Information System (INIS)

    Sease, J.D.

    1983-01-01

    In DOE defense operations, approx. 70,000 m 3 of beta-gamma low-level radioactive waste are disposed of annually by shallow land burial operations at six primary sites. Waste generated at other DOE sites are transported on public roads to the primary sites for disposal. In the practice of low-level waste (LLW) disposal in the US, the site hydrology and geology are the primary barriers to radioactive migration. To date, little emphasis has been placed on waste form improvements or engineered site modifications to reduce migration potential. Compaction is the most common treatment step employed. The performance of ground disposal of radioactive waste in this country, in spite of many practices that we would consider unacceptable in today's light, has resulted in very little migration of radioactivity outside site boundaries. Most problems with previously used burial grounds have been from subsidence at the arid sites and subsidence and groundwater contact at the humid sites. The radionuclides that have shown the most significant migration are tritium, 90 Sr, and 99 Tc. The unit cost for disposal operations at a given DOE site is dependent on many variables, but the annual volume to be disposed is probably the major factor. The average cost for current DOE burial operation is approximately $170/m 3 . 23 figures

  16. Influence of beta radiation from tritium and gamma radiation from 60Co on the biological half-times of organically bound tritium

    International Nuclear Information System (INIS)

    Radwan, I.

    1981-01-01

    The influence of beta radiation from tritium on the biological half-times of organically bound tritium in particular tissues of the rat is compred with the influence of fractionated gamma radiation from 60 Co. (M.F.W.)

  17. Efficacy of gamma interferon and specific antibody for treatment of microsporidiosis caused by Encephalitozoon cuniculi in SCID mice

    Czech Academy of Sciences Publication Activity Database

    Salát, Jiří; Jelínek, Jiří; Chmelař, Jindřich; Kopecký, Jan

    2008-01-01

    Roč. 52, č. 6 (2008), s. 2169-2174 ISSN 0066-4804 R&D Projects: GA ČR GP524/03/D167; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : murine peritoneal-macrophages * IFN-gamma * immune-response * T-lymphocytes * infection * cells * therapy * AIDS * CD4+ Subject RIV: EC - Immunology Impact factor: 4.716, year: 2008

  18. A triple-crystal phoswich detector with digital pulse shape discrimination for alpha/beta/gamma spectroscopy

    International Nuclear Information System (INIS)

    White, Travis L.; Miller, William H.

    1999-01-01

    Researchers at the University of Missouri - Columbia have developed a three-crystal phoswich detector coupled to a digital pulse shape discrimination system for use in alpha/beta/gamma spectroscopy. Phoswich detectors use a sandwich of scintillators viewed by a single photomultiplier tube to simultaneously detect multiple types of radiation. Separation of radiation types is based upon pulse shape difference among the phosphors, which has historically been performed with analog circuitry. The system uses a GaGe CompuScope 1012, 12 bit, 10 MHz computer-based oscilloscope that digitally captures the pulses from a phoswich detector and subsequently performs pulse shape discrimination with cross-correlation analysis. The detector, based partially on previous phoswich designs by Usuda et al., uses a 10 mg/cm 2 thick layer of ZnS(Ag) for alpha detection, followed by a 0.254 cm CaF 2 (Eu) crystal for beta detection, all backed by a 2.54 cm NaI(Tl) crystal for gamma detection. Individual energy spectra and count rate information for all three radiation types are displayed and updated periodically. The system shows excellent charged particle discrimination with an accuracy of greater than 99%. Future development will include a large area beta probe with gamma-ray discrimination, systems for low-energy photon detection (e.g. Bremsstrahlung or keV-range photon emissions), and other health physics instrumentation

  19. Hypoxia upregulates Bcl-2 expression and suppresses interferon-gamma induced antiangiogenic activity in human tumor derived endothelial cells.

    LENUS (Irish Health Repository)

    Wang, Jiang Huai

    2012-02-03

    BACKGROUND: Hypoxia in solid tumors potentially stimulates angiogenesis by promoting vascular endothelial growth factor (VEGF) production and upregulating VEGF receptor expression. However, it is unknown whether hypoxia can modulate the effect of anti-angiogenic treatment on tumor-derived endothelium. METHODS: Human tumor-derived endothelial cells (HTDEC) were freshly isolated from surgically removed human colorectal tumors by collagenase\\/DNase digestion and Percol gradient sedimentation. Cell proliferation was assessed by measuring BrdU incorporation, and capillary tube formation was measured using Matrigel. Cell apoptosis was assessed by flow cytometry and ELISA, and Bcl-2 expression was detected by Western blot analysis. RESULTS: Under aerobic culture conditions (5% CO2 plus 21% O2) HTDEC expressed less Bcl-2 and were more susceptible to IFN-gamma-induced apoptosis with significant reductions in both cell proliferation and capillary tube formation, when compared with normal human macrovascular and microvascular EC. Following exposure of HTDEC to hypoxia (5% CO2 plus 2% O2), IFN-gamma-induced cell apoptosis, and antiangiogenic activity (i.e. an inhibition in cell proliferation and capillary tube formation) in HTDEC were markedly attenuated. This finding correlated with hypoxia-induced upregulation of Bcl-2 expression in HTDEC. CONCLUSIONS: These results indicate that hypoxia can protect HTDEC against IFN-gamma-mediated cell death and antiangiogenic activity, and suggest that improvement of tumor oxygenation may potentiate the efficacy of anti-cancer therapies specifically targeting the inhibition of tumor angiogenesis.

  20. Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats

    Science.gov (United States)

    Yu, Hong-Ren; Tain, You-Lin; Sheen, Jiunn-Ming; Tiao, Mao-Meng; Chen, Chih-Cheng; Kuo, Ho-Chang; Hung, Pi-Lien; Hsieh, Kai-Sheng; Huang, Li-Tung

    2016-01-01

    Overexposure to prenatal glucocorticoid (GC) disturbs hypothalamic-pituitary-adrenocortical axis-associated neuroendocrine metabolism and susceptibility to metabolic syndrome. A high-fat (HF) diet is a major environmental factor that can cause metabolic syndrome. We aimed to investigate whether prenatal GC plus a postnatal HF diet could alter immune programming in rat offspring. Pregnant Sprague-Dawley rats were given intraperitoneal injections of dexamethasone or saline at 14–21 days of gestation. Male offspring were then divided into four groups: vehicle, prenatal dexamethasone exposure, postnatal HF diet (VHF), and prenatal dexamethasone exposure plus a postnatal HF diet (DHF). The rats were sacrificed and adaptive immune function was evaluated. Compared to the vehicle, the DHF group had lower interferon gamma (IFN-γ) production by splenocytes at postnatal day 120. Decreases in H3K9 acetylation and H3K36me3 levels at the IFN-γ promoter correlated with decreased IFN-γ production. The impaired IFN-γ production and aberrant site-specific histone modification at the IFN-γ promoter by prenatal dexamethasone treatment plus a postnatal HF diet resulted in resilience at postnatal day 180. Prenatal dexamethasone and a postnatal HF diet decreased IFN-γ production through a site-specific and an age-dependent histone modification. These findings suggest a mechanism by which prenatal exposure to GC and a postnatal environment exert effects on fetal immunity programming. PMID:27669212

  1. Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Hong-Ren Yu

    2016-09-01

    Full Text Available Overexposure to prenatal glucocorticoid (GC disturbs hypothalamic-pituitary-adrenocortical axis-associated neuroendocrine metabolism and susceptibility to metabolic syndrome. A high-fat (HF diet is a major environmental factor that can cause metabolic syndrome. We aimed to investigate whether prenatal GC plus a postnatal HF diet could alter immune programming in rat offspring. Pregnant Sprague-Dawley rats were given intraperitoneal injections of dexamethasone or saline at 14–21 days of gestation. Male offspring were then divided into four groups: vehicle, prenatal dexamethasone exposure, postnatal HF diet (VHF, and prenatal dexamethasone exposure plus a postnatal HF diet (DHF. The rats were sacrificed and adaptive immune function was evaluated. Compared to the vehicle, the DHF group had lower interferon gamma (IFN-γ production by splenocytes at postnatal day 120. Decreases in H3K9 acetylation and H3K36me3 levels at the IFN-γ promoter correlated with decreased IFN-γ production. The impaired IFN-γ production and aberrant site-specific histone modification at the IFN-γ promoter by prenatal dexamethasone treatment plus a postnatal HF diet resulted in resilience at postnatal day 180. Prenatal dexamethasone and a postnatal HF diet decreased IFN-γ production through a site-specific and an age-dependent histone modification. These findings suggest a mechanism by which prenatal exposure to GC and a postnatal environment exert effects on fetal immunity programming.

  2. Continuous in vivo infusion of interferon-gamma (IFN-γ) enhances engraftment of syngeneic wild-type cells in Fanca–/– and Fancg–/– mice

    Science.gov (United States)

    Si, Yue; Ciccone, Samantha; Yang, Feng-Chun; Yuan, Jin; Zeng, Daisy; Chen, Shi; van de Vrugt, Henri J.; Critser, John; Arwert, Fre; Haneline, Laura S.; Clapp, D. Wade

    2006-01-01

    Fanconi anemia (FA) is a heterogeneous genetic disorder characterized by bone marrow (BM) failure and cancer susceptibility. Identification of the cDNAs of FA complementation types allows the potential of using gene transfer technology to introduce functional cDNAs as transgenes into autologous stem cells and provide a cure for the BM failure in FA patients. However, strategies to enhance the mobilization, transduction, and engraftment of exogenous stem cells are required to optimize efficacy prior to widespread clinical use. Hypersensitivity of Fancc–/– cells to interferon-gamma (IFN-γ), a nongenotoxic immune-regulatory cytokine, enhances engraftment of syngeneic wild-type (WT) cells in Fancc–/– mice. However, whether this phenotype is of broad relevance in other FA complementation groups is unresolved. Here we show that primitive and mature myeloid progenitors in Fanca–/– and Fancg–/– mice are hypersensitive to IFN-γ and that in vivo infusion of IFN-γ at clinically relevant concentrations was sufficient to allow consistent long-term engraftment of isogenic WT repopulating stem cells. Given that FANCA, FANCC, and FANCG complementation groups account for more than 90% of all FA patients, these data provide evidence that IFN-γ conditioning may be a useful nongenotoxic strategy for myelopreparation in FA patients. PMID:16946306

  3. The gene-immune-behavioral pathway: Gamma-interferon (IFN-γ) simultaneously coordinates susceptibility to infectious disease and harm avoidance behaviors.

    Science.gov (United States)

    MacMurray, James; Comings, David E; Napolioni, Valerio

    2014-01-01

    Cytokine gene variants are known to influence both infectious disease susceptibility and harm-avoidant behaviors, suggesting that these risk variants may be pleiotropically linked to instinctual disease-avoidant traits. The gamma-interferon (IFNG) +874 T>A polymorphism (rs2430561) is an ideal candidate gene variant for immune-behavioral studies. It is a functional SNP, regulating IFNG mRNA expression; it is known to modulate serotonergic activity and is therefore capable of modifying behavior; and it has previously been associated with increased susceptibility to malaria, tuberculosis, leprosy and Chagas disease. We hypothesized that the infectious disease-high-risk IFNG +874 A-allele would be associated with four personality traits previously reported as behavioral defenses against infection: Harm Avoidance (HA), Extraversion (E), Exploratory Excitability (Exp E), and Openness to Experience (O). We tested this hypothesis in a sample of 168 healthy university students from Southern California genotyped for IFNG +874 T>A and evaluated by the Temperament and Character Inventory-Revised (TCI-R) and the NEO Five-Factor Inventory (NEO-FFI). We found that the infectious disease-high-risk IFNG +874 A-allele was associated with increased HA (P=0.001) and decreased E (P=0.030) and Exp E (P=0.030). These findings suggest that the IFNG +874 A gene variant is linked both to infectious disease susceptibility and to proactive behavioral defenses that reduce infection risk in healthy subjects. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Macrophage-Lineage Cells Negatively Regulate the Hematopoietic Stem Cell Pool in Response to Interferon Gamma at Steady State and During Infection.

    Science.gov (United States)

    McCabe, Amanda; Zhang, Yubin; Thai, Vinh; Jones, Maura; Jordan, Michael B; MacNamara, Katherine C

    2015-07-01

    Bone marrow (BM) resident macrophages (Mϕs) regulate hematopoietic stem cell (HSC) mobilization; however, their impact on HSC function has not been investigated. We demonstrate that depletion of BM resident Mϕs increases HSC proliferation as well as the pool of quiescent HSCs. At the same time, during bacterial infection where BM resident Mϕs are selectively increased we observe a decrease in HSC numbers. Moreover, strategies that deplete or reduce Mϕs during infection prevent HSC loss and rescue HSC function. We previously found that the transient loss of HSCs during infection is interferon-gamma (IFNγ)-dependent. We now demonstrate that IFNγ signaling specifically in Mϕs is critical for both the diminished HSC pool and maintenance of BM resident Mϕs during infection. In addition to the IFNγ-dependent loss of BM HSC and progenitor cells (HSPCs) during infection, IFNγ reduced circulating HSPC numbers. Importantly, under infection conditions AMD3100 or G-CSF-induced stem cell mobilization was impaired. Taken together, our data show that IFNγ acts on Mϕs, which are a negative regulator of the HSC pool, to drive the loss in BM and peripheral HSCs during infection. Our findings demonstrate that modulating BM resident Mϕ numbers can impact HSC function in vivo, which may be therapeutically useful for hematologic conditions and refinement of HSC transplantation protocols. © 2015 AlphaMed Press.

  5. Effect of Pregnancy on Interferon Gamma Release Assay and Tuberculin Skin Test Detection of Latent TB Infection Among HIV-Infected Women in a High Burden Setting.

    Science.gov (United States)

    LaCourse, Sylvia M; Cranmer, Lisa M; Matemo, Daniel; Kinuthia, John; Richardson, Barbra A; Horne, David J; John-Stewart, Grace

    2017-05-01

    Peripartum immunologic changes may affect latent tuberculosis infection (LTBI) diagnostic performance among HIV-infected women. HIV-infected women were serially tested with tuberculin skin test (TST) and interferon gamma release assay [QuantiFERON TB Gold In-tube (QFT)] in pregnancy and 6 weeks postpartum in Kenya. Prevalence, sensitivity and agreement, and correlates of QFT/TST positivity were assessed. Quantitative QFT mitogen and Mycobacterium tuberculosis antigen (Mtb-Ag) responses were compared by peripartum stage. Incidence of test conversion at 6 weeks postpartum was evaluated in baseline TST-/QFT- women. Among 100 HIV-infected women, median age was 26 years, median CD4 was 555 cells per cubic millimeter, and 88% were on antiretrovirals. More women were QFT+ than TST+ in both pregnancy (35.4% vs. 13.5%, P = 0.001) and postpartum (29.6% vs. 14.8%, P pregnancy vs. postpartum, and specifically among persistently QFT+ women (Mtb-Ag: 3.46 vs. 4.48 IU/mL, P = 0.007). QFT indeterminate rate was higher in pregnancy (16%) compared with postpartum (0%) because of lower mitogen response. QFT identified >2-fold more women with LTBI compared with TST in pregnancy and postpartum. Lower QFT Mtb-Ag and mitogen responses in pregnancy compared with postpartum suggest that pregnancy-associated immunologic changes may influence LTBI test performance.

  6. Methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN study): a multicentre, double-blind, randomised, placebo-controlled, parallel-group trial

    DEFF Research Database (Denmark)

    Ravnborg, Mads; Sørensen, Per Soelberg; Andersson, Magnus

    2010-01-01

    status scale (EDSS) score of 4 or less. Patients all started to receive interferon beta-1a and after 3 months were randomly assigned to add-on methylprednisolone or placebo 500 mg/day orally for 3 consecutive days per month for 3-4 years. Placebo tablets were identical to methylprednisolone tablets....... Treating physicians, examining physicians, and patients were masked to treatment allocation. Patients were clinically assessed every 3 months and had brain MRI at baseline and 3 years later. The primary outcome was time to onset of disability progression, according to an increase in EDSS score sustained...

  7. High Resistance of Human Parainfluenza Type 2 Virus Protein-Expressing Cells to the Antiviral and Anti-Cell Proliferative Activities of Alpha/Beta Interferons: Cysteine-Rich V-Specific Domain Is Required for High Resistance to the Interferons

    OpenAIRE

    Nishio, Machiko; Tsurudome, Masato; Ito, Morihiro; Kawano, Mitsuo; Komada, Hiroshi; Ito, Yasuhiko

    2001-01-01

    Human parainfluenza type 2 virus (hPIV-2)-infected HeLa (HeLa-CA) cells and hPIV-2 V-expressing HeLa (HeLa-V) cells show high resistance to alpha/beta interferons (IFN-α/β) irrespective of whether vesicular stomatitis virus or Sindbis virus is used as a challenge virus. When Sindbis virus is used, these cells show high susceptibility to human IFN-γ. Furthermore, the multiplication of HeLa-V cells is not inhibited by IFN-α/β. HeLa cells expressing the N-terminally truncated V protein show resi...

  8. Staphylococcal enterotoxin-A directly stimulates signal transduction and interferon-gamma production in psoriatic T-cell lines

    DEFF Research Database (Denmark)

    Nielsen, M B; Odum, N; Gerwien, J

    1998-01-01

    class II. Here we address the question of whether SEA can directly activate psoriatic T cells in the absence of professional antigen-presenting cells. We show that SEA induces i) tyrosine phosphorylation of several proteins, ii) downregulation of the T-cell receptor (TCR), and iii) production......-mediated proliferation. In contrast, SEA with a mutation in the MHC class II alpha-binding site induces IFN-gamma and a qualitatively changed tyrosine phosphorylation profile. Both mutations delete the co-stimulatory effect on cytokine-mediated proliferation. This suggests that both MHC class II binding sites...

  9. Studies of. gamma. -ray irradiation effects on tris(. beta. -diketonato)iron(III) and cobalt(III) coordination compounds by means of Moessbauer spectroscopy and magnetic susceptibility measurements

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Y.; Endo, K.; Sano, H. (Tokyo Metropolitan Univ. (Japan). Faculty of Science)

    1981-06-01

    Both absorption Moessbauer spectroscopy and magnetic susceptibility measurements on tris(..beta..-diketonato)iron(III) and cobalt(III) compounds indicate that ligands which have phenyl group as a substituent are more stable to ..gamma..-ray radiolysis, in accordance with previous results of emission Moessbauer spectroscopic studies of /sup 57/Co-labelled tris (..beta..-diketonato)cobalt(III) compounds.

  10. Development and validation of cell-based luciferase reporter gene assays for measuring neutralizing anti-drug antibodies against interferon beta.

    Science.gov (United States)

    Hermanrud, Christina; Ryner, Malin; Luft, Thomas; Jensen, Poul Erik; Ingenhoven, Kathleen; Rat, Dorothea; Deisenhammer, Florian; Sørensen, Per Soelberg; Pallardy, Marc; Sikkema, Dan; Bertotti, Elisa; Kramer, Daniel; Creeke, Paul; Fogdell-Hahn, Anna

    2016-03-01

    Neutralizing anti-drug antibodies (NAbs) against therapeutic interferon beta (IFNβ) in people with multiple sclerosis (MS) are measured with cell-based bioassays. The aim of this study was to redevelop and validate two luciferase reporter-gene bioassays, LUC and iLite, using a cut-point approach to identify NAb positive samples. Such an approach is favored by the pharmaceutical industry and governmental regulatory agencies as it has a clear statistical basis and overcomes the limitations of the current assays based on the Kawade principle. The work was conducted following the latest assay guidelines. The assays were re-developed and validated as part of the "Anti-Biopharmaceutical Immunization: Prediction and analysis of clinical relevance to minimize the risk" (ABIRISK) consortium and involved a joint collaboration between four academic laboratories and two pharmaceutical companies. The LUC assay was validated at Innsbruck Medical University (LUCIMU) and at Rigshospitalet (LUCRH) Copenhagen, and the iLite assay at Karolinska Institutet, Stockholm. For both assays, the optimal serum sample concentration in relation to sensitivity and recovery was 2.5% (v/v) in assay media. A Shapiro-Wilk test indicated a normal distribution for the majority of runs, allowing a parametric approach for cut-point calculation to be used, where NAb positive samples could be identified with 95% confidence. An analysis of means and variances indicated that a floating cut-point should be used for all assays. The assays demonstrated acceptable sensitivity for being cell-based assays, with a confirmed limit of detection in neat serum of 1519 ng/mL for LUCIMU, 814 ng/mL for LUCRH, and 320 ng/mL for iLite. Use of the validated cut-point assay, in comparison with the previously used Kawade method, identified 14% more NAb positive samples. In conclusion, implementation of the cut-point design resulted in increased sensitivity to detect NAbs. However, the clinical significance of these low

  11. Efficacy of post operative adjuvant therapy with human interferon beta, MCNU and radiation (IMR) for malignant glioma: comparison among three protocols

    International Nuclear Information System (INIS)

    Hatano, N.; Wakabayashi, T.; Kajita, Y.; Mizuno, M.; Ohno, T.; Nakayashiki, N.; Takemura, A.; Yoshida, J.

    2000-01-01

    In order to develop ultimate adjuvant therapy for malignant gliomas, we analyzed 77 patients with malignant gliomas (29 anaplastic astrocytomas (AAs) and 48 glioblastoma multiformes (GMs)) treated by three protocols of IMR therapy (human interferon-beta (HuIFN-β), MCNU and radiation). In protocol 1 (n = 45 : AA = 13, GM = 32), 1 x 10 6 IU of HuIFN-β was administrated intravenously once a day for 7 days. On day 2, MCNU was administrated at a dose of 2 mg/kg b.w. intravenously and from day 3, radiation was started in five weekly fractions of 2 Gy for 6 weeks. Total dose was 60 Gy. Protocol 2 (n = 19 : AA = 11, GM = 8) was comparable with protocol 1 except HuIFN-β was administrated twice a day at a dose of 1 x 10 6 IU each. Protocol 3 (n = 13 : AA = 5, GM = 8) differed from protocol 2 only in a high dose-hyperfractionated radiation which was given twice a day at a dose of 1.5 Gy each and for a total dose of 66 Gy. Antitumor effects were evaluated by survival and response rate determined by decrease of tumor size. Significant improvement was obtained in patients with AAs by protocol 2 and 3. Response rates of patients with AAs and GMs were 46.2 % and 50 % in protocol 1, 63.6 % and 50 % in protocol 2, and 80 % and 50 % in protocol 3, respectively. One and two year survival rates in AAs were 46.4 % and 34.8 % in protocol 1, both 75 % in protocol 2, and both 100 % in protocol 3. Survival rates in GMs were not different among them. Except of radiation necrosis, which was observed in 38.5 % of the patients under protocol 3, there was no significant difference in the adverse effects among the three protocols. In the present study, the efficacy of IMR therapy for patients with malignant gliomas, especially for AAs, was confirmed. We conclude that twice a day administrations of HuIFN-β in combination with a high dose-hyperfractionated radiation provide increased efficacy in IMR therapy. (author)

  12. Primary 4{pi}{beta}-{gamma} coincidence system for standardization of radionuclides by means of plastic scintillators; Sistema primario por coincidencias 4{pi}{beta}-{gamma} para a padronizacao de radionuclideos empregando cintiladores plasticos

    Energy Technology Data Exchange (ETDEWEB)

    Baccarelli, Aida Maria

    2003-07-01

    The present work describes a 4{pi}({alpha},{beta})-{gamma} coincidence system for absolute measurement of radionuclide activity using a plastic scintillator in 4{pi} geometry for charged particles detection and a Nal (Tl) crystal for gamma-ray detection. Several shapes and dimensions of the plastic scintillator have been tried in order to obtain the best system configuration. Radionuclides which decay by alpha emission, {beta}{sup -}, {beta}{sup +} and electron capture have been standardized. The results showed excellent agreement with other conventional primary system which makes use of a 4{pi} proportional counter for X-ray and charged particle detection. The system developed in the present work have some advantages when compared with the conventional systems, namely; it does not need metal coating on the films used as radioactive source holders. When compared to liquid scintillators, is showed the advantage of not needing to be kept in dark for more than 24 h to allow phosphorescence decay of ambient light. Therefore it can be set to count immediately after the sources are placed inside of it. (author)

  13. Category-specific visual responses: an intracranial study comparing gamma, beta, alpha and ERP response selectivity

    Directory of Open Access Journals (Sweden)

    Juan R Vidal

    2010-11-01

    Full Text Available The specificity of neural responses to visual objects is a major topic in visual neuroscience. In humans, functional magnetic resonance imaging (fMRI studies have identified several regions of the occipital and temporal lobe that appear specific to faces, letter-strings, scenes, or tools. Direct electrophysiological recordings in the visual cortical areas of epileptic patients have largely confirmed this modular organization, using either single-neuron peri-stimulus time-histogram or intracerebral event-related potentials (iERP. In parallel, a new research stream has emerged using high-frequency gamma-band activity (50-150 Hz (GBR and low-frequency alpha/beta activity (8-24 Hz (ABR to map functional networks in humans. An obvious question is now whether the functional organization of the visual cortex revealed by fMRI, ERP, GBR, and ABR coincide. We used direct intracerebral recordings in 18 epileptic patients to directly compare GBR, ABR, and ERP elicited by the presentation of seven major visual object categories (faces, scenes, houses, consonants, pseudowords, tools, and animals, in relation to previous fMRI studies. Remarkably both GBR and iERP showed strong category-specificity that was in many cases sufficient to infer stimulus object category from the neural response at single-trial level. However, we also found a strong discrepancy between the selectivity of GBR, ABR, and ERP with less than 10% of spatial overlap between sites eliciting the same category-specificity. Overall, we found that selective neural responses to visual objects were broadly distributed in the brain with a prominent spatial cluster located in the posterior temporal cortex. Moreover, the different neural markers (GBR, ABR, and iERP that elicit selectivity towards specific visual object categories present little spatial overlap suggesting that the information content of each marker can uniquely characterize high-level visual information in the brain.

  14. CD147 is a regulatory subunit of the gamma-secretase complex inAlzheimer's disease amyloid beta-peptide production

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Shuxia; Zhou, Hua; Walian, Peter J.; Jap, Bing K.

    2005-04-06

    {gamma}-secretase is a membrane protein complex that cleaves the {beta}-amyloid precursor protein (APP) within the transmembrane region, following prior processing by {beta}-secretase, producing amyloid {beta}-peptides (A{beta}{sub 40} and A{beta}{sub 42}). Errant production of A{beta}-peptides that substantially increases A{beta}{sub 42} production has been associated with the formation of amyloid plaques in Alzheimer's disease patients. Biophysical and genetic studies indicate that presenilin-1 (Psn-1), which contains the proteolytic active site, and three other membrane proteins, nicastrin (Nct), APH-1, and PEN-2 are required to form the core of the active {gamma}-secretase complex. Here, we report the purification of the native {gamma}-secretase complexes from HeLa cell membranes and the identification of an additional {gamma}-secretase complex subunit, CD147, a transmembrane glycoprotein with two immunoglobulin-like domains. The presence of this subunit as an integral part of the complex itself was confirmed through co-immunoprecipitation studies of the purified protein from HeLa cells and solubilized complexes from other cell lines such as neural cell HCN-1A and HEK293. Depletion of CD147 by RNA interference was found to increase the production of A{beta} peptides without changing the expression level of the other {gamma}-secretase components or APP substrates while CD147 overexpression had no statistically significant effect on amyloid {beta}-peptide production, other {gamma}-secretase components or APP substrates, indicating that the presence of the CD147 subunit within the {gamma}-secretase complex directly down-modulates the production of A{beta}-peptides. {gamma}-secretase was first recognized through its role in the production of the A{beta} peptides that are pathogenic in Alzheimer's disease (AD) (1). {gamma}-secretase is a membrane protein complex with unusual aspartyl protease activity that cleaves a variety of type I membrane proteins

  15. Attenuation of beta and gamma oscillations in schizophrenia spectrum patients following hand posture perturbation

    DEFF Research Database (Denmark)

    Arnfred, Sidse M.; Mørup, Morten; Thalbitzer, Jørgen

    2011-01-01

    Several electroencephalographic (EEG) studies in schizophrenia report that the patients have reduced evoked gamma activity following visual and auditory stimulation. Somatosensory gamma activity has not previously been examined. It has been suggested that a dysfunction basic to schizophrenia spec...

  16. Beta-and gamma-turns in proteins revisited: a new set of amino acid turn-type dependent positional preferences and potentials.

    Science.gov (United States)

    Guruprasad, K; Rajkumar, S

    2000-06-01

    The number of beta-turns in a representative set of 426 protein three-dimensional crystal structures selected from the recent Protein Data Bank has nearly doubled and the number of gamma-turns in a representative set of 320 proteins has increased over seven times since the previous analysis. Beta-turns (7153) and gamma-turns (911) extracted from these proteins were used to derive a revised set of type-dependent amino acid positional preferences and potentials. Compared with previous results, the preference for proline, methionine and tryptophan has increased and the preference for glutamine, valine, glutamic acid and alanine has decreased for beta-turns. Certain new amino acid preferences were observed for both turn types and individual amino acids showed turn-type dependent positional preferences. The rationale for new amino acid preferences are discussed in the light of hydrogen bonds and other interactions involving the turns. Where main-chain hydrogen bonds of the type NH(i + 3) --> CO(i) were not observed for some beta-turns, other main-chain hydrogen bonds or solvent interactions were observed that possibly stabilize such beta-turns. A number of unexpected isolated beta-turns with proline at i + 2 position were also observed. The NH(i + 2) --> CO(i) hydrogen bond was observed for almost all gamma-turns. Nearly 20% classic gamma-turns and 43% inverse gamma-turns are isolated turns.

  17. Comparison of gamma- and beta radiation stress responses on anti-oxidative defense system and DNA modifications in Lemna minor

    Energy Technology Data Exchange (ETDEWEB)

    Van Hoeck, Arne [SCK.CEN, Boeretang 200 2400 Mol (Belgium); University of Antwerp, Groenenborgerlaan 171, 2020 Antwerpen (Belgium); Horemans, Nele; Van Hees, May; Nauts, Robin; Vandenhove, Hildegarde [SCK.CEN, Boeretang 200 2400 Mol (Belgium); Knapen, Dries; Blust, Ronny [University of Antwerp, Groenenborgerlaan 171, 2020 Antwerpen (Belgium)

    2014-07-01

    The biological effects and interactions of different radiation types in plants are still far from understood. Additional knowledge on the impact of various kinds of ionizing radiation in plants on individual, biochemical and molecular level is needed to unravel and compare the toxic mode of action. Among different radiation types, external gamma radiation treatments have been mostly studied both in lab and field studies to derive the biological impact of radiation toxicity in organisms. However, environmental relevant studies on chronic low-dose gamma exposures are scarce. The radio-ecologically relevant radionuclide {sup 90}Sr is a pure beta emitting isotope and originates from nuclear activities and accidents. Although this radionuclide is not essential for plant metabolism, it bears a chemical analogy with the essential plant macro-nutrient Ca{sup 2+} thereby taking advantage of Ca{sup 2+} transport systems to contaminate plant organs and tissues. Ones plants are exposed to radiation stress, ionization events can cause an increase in reactive oxygen species (ROS) and can induce damage to biological material like DNA, lipids and structural proteins. The following work aimed at evaluating individual, biochemical and molecular endpoints to understand and to compare the mode of action of gamma- and beta radiation stress in plants. Having an equal relative biological effectiveness to non-human biota, it is still not clear in how plants differ or overlap in sensing and interpreting highly penetrating electromagnetic radiation with short-range particle radiation. The floating plant Lemna minor was chosen as model system. Following the OECD guidelines Lemna plants were being exposed separately to an external gamma radiation source or to a {sup 90}Sr-contaminated growth medium to obtain single-dose response curves for each type of radiation. In order to acquire accurate dose rate quantifications for beta radiation exposures, {sup 90}Sr uptake and accumulation of root and

  18. Determination of gamma and-2 beta(s) from charmless two-body decays of beauty mesons

    NARCIS (Netherlands)

    Aaij, R.; Beteta, C. Abellan; Adeva, B.; Adinolfi, M.; Affolder, A.; Ajaltouni, Z.; Akar, S.; Albrecht, J.; Alessio, F.; Alexander, M.; Ali, S.; Alkhazov, G.; Cartelle, P. Alvarez; Alves, A. A.; Amato, S.; Amerio, S.; Amhis, Y.; An, L.; Anderlini, L.; Anderson, J.; Andreassen, R.; Andreotti, M.; Andrews, J. E.; Appleby, R. B.; Gutierrez, O. Aquines; Archilli, F.; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Baalouch, M.; Bachmann, S.; Back, J. J.; Badalov, A.; Baesso, C.; Baldini, W.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Batozskaya, V.; Battista, V.; Bay, A.; Beaucourt, L.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Belogurov, S.; Belous, K.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Benton, J.; Berezhnoy, A.; Bernet, R.; Bettler, M. -O.; van Beuzekom, M.; Bien, A.; Bifani, S.; Bird, T.; Bizzeti, A.; Bjornstad, P. M.; Blake, T.; Blanc, F.; Blouw, J.; Blusk, S.; Bocci, V.; Bondar, A.; Bondar, N.; Bonivento, W.; Borghi, S.; Borgia, A.; Borsato, M.; Bowcock, T. J. V.; Bowen, E.; Bozzi, C.; Brambach, T.; Bressieux, J.; Brett, D.; Britsch, M.; Britton, T.; Brodzicka, J.; Brook, N. H.; Brown, H.; Bursche, A.; Busetto, G.; Buytaert, J.; Cadeddu, S.; Calabrese, R.; Calvi, M.; Gomez, M. Calvo; Campana, P.; Perez, D. Campora; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carson, L.; Akiba, K. Carvalho; Casse, G.; Cassina, L.; Garcia, L. Castillo; Cattaneo, M.; Cauet, Ch.; Cenci, R.; Charles, M.; Charpentier, Ph.; Chefdeville, M.; Chen, S.; Cheung, S. -F.; Chiapolini, N.; Chrzaszcz, M.; Ciba, K.; Vidal, X. Cid; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Coco, V.; Cogan, J.; Cogneras, E.; Cojocariu, L.; Collins, P.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombes, M.; Coquereau, S.; Corti, G.; Corvo, M.; Counts, I.; Couturier, B.; Cowan, G. A.; Craik, D. C.; Torres, M. Cruz; Cunliffe, S.; Currie, R.; D'Ambrosio, C.; Dalseno, J.; David, P.; David, P. N. Y.; Davis, A.; De Bruyn, K.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Silva, W.; De Simone, P.; De camp, D.; Deckenhoff, M.; Del Buono, L.; Deleage, N.; Derkach, D.; Deschamps, O.; Dettori, F.; Di anto, A.; Dijkstra, H.; Donleavy, S.; Dordei, F.; Dorigo, M.; Suarez, A. Dosil; Dossett, D.; Dovbnya, A.; Dreimanis, K.; Dujany, G.; Dupertuis, F.; Durante, P.; Dzhelyadin, R.; Dziurda, A.; Dzyuba, A.; Easo, S.; Egorychev, V.; Eidelman, S.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; El Rifai, I.; Elsasser, Ch.; Ely, S.; Esen, S.; Evans, H. -M.; Evans, T.; Falabella, A.; Faerber, C.; Farinelli, C.; Farley, N.; Farry, S.; Fay, R. F.; Ferguson, D.; Albor, V. Fernandez; Rodrigues, F. Ferreira; Ferro-Luzzi, M.; Filippov, S.; Fiore, M.; Fiorini, M.; Firlej, M.; Fitzpatrick, C.; Fiutowski, T.; Fol, P.; Fontana, M.; Fontanelli, F.; Forty, R.; Francisco, O.; Frank, M.; Frei, C.; Frosini, M.; Fu, J.; Furfaro, E.; Torreira, A. Gallas; Galli, D.; Gallorini, S.; Gambetta, S.; Gandelman, M.; Gandini, P.; Gao, Y.; Pardinas, J. Garca; Garofoli, J.; Tico, J. Garra; Garrido, L.; Gaspar, C.; Gauld, R.; Gavardi, L.; Gavrilov, G.; Geraci, A.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph.; Gianelle, A.; Giani, S.; Gibson, V.; Giubega, L.; Gligorov, V. V.; Goebel, C.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gotti, C.; Gandara, M. Grabalosa; Diaz, R. Graciani; Cardoso, L. A. Granado; Grauges, E.; Graziani, G.; Grecu, A.; Greening, E.; Gregson, S.; Griffith, P.; Grillo, L.; Gruenberg, O.; Gui, B.; Gushchin, E.; Guz, Yu.; Gys, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hall, S.; Hamilton, B.; Hampson, T.; Han, X.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Harrison, J.; He, J.; Head, T.; Heijne, V.; Hennessy, K.; Henrard, P.; Henry, L.; Morata, J. A. Hernando; van Herwijnen, E.; Hess, M.; Hicheur, A.; Hill, D.; Hoballah, M.; Hombach, C.; Hulsbergen, W.; Hunt, P.; Hussain, N.; Hutchcroft, D.; Hynds, D.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jaeger, A.; Jalocha, J.; Jans, E.; Jaton, P.; Jawahery, A.; Jing, F.; John, M.; Johnson, D.; Jones, C. R.; Joram, C.; Jost, B.; Jurik, N.; Kaballo, M.; Kandybei, S.; Kanso, W.; Karacson, M.; Karbach, T. M.; Karodia, S.; Kelsey, M.; Kenyon, I. R.; Ketel, T.; Khanji, B.; Khurewathanakul, C.; Klaver, S.; Klimaszewski, K.; Kochebina, O.; Kolpin, M.; Komarov, I.; Koopman, R. F.; Koppenburg, P.; Korolev, M.; Kozlinskiy, A.; Kravchuk, L.; Kreplin, K.; Kreps, M.; Krocker, G.; Krokovny, P.; Kruse, F.; Kucewicz, W.; Kucharczyk, M.; Kudryavtsev, V.; Kurek, K.; Kvaratskheliya, T.; La Thi, V. N.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lambert, D.; Lambert, R. W.; Lanfranchi, G.; Langenbruch, C.; Langhans, B.; Latham, T.; Lazzeroni, C.; Le Gac, R.; van Leerdam, J.; Lees, J. -P.; Lefevre, R.; Leflat, A.; Lefrancois, J.; Leo, S.; Leroy, O.; Lesiak, T.; Leverington, B.; Li, Y.; Likhomanenko, T.; Liles, M.; Lindner, R.; Linn, C.; Lionetto, F.; Liu, B.; Lohn, S.; Longstaff, I.; Lopes, J. H.; Lopez-March, N.; Lowdon, P.; Lu, H.; Lucchesi, D.; Luo, H.; Lupato, A.; Luppi, E.; Lupton, O.; Machefert, F.; Machikhiliyan, I. V.; Maciuc, F.; Maev, O.; Malde, S.; Malinin, A.; Manca, G.; Mancinelli, G.; Mapelli, A.; Maratas, J.; Marchand, J. F.; Marconi, U.; Benito, C. Marin; Marino, P.; Maerki, R.; Marks, J.; Martellotti, G.; Martens, A.; Sanchez, A. Martn; Martinelli, M.; Santos, D. Martinez; Vidal, F. Martinez; Tostes, D. Martins; Massafferri, A.; Matev, R.; Mathe, Z.; Matteuzzi, C.; Mazurov, A.; McCann, M.; McCarthy, J.; Mcnab, A.; McNulty, R.; McSkelly, B.; Meadows, B.; Meier, F.; Meissner, M.; Merk, M.; Milanes, D. A.; Minard, M. -N.; Moggi, N.; Rodriguez, J. Molina; Monteil, S.; Morandin, M.; Morawski, P.; Morda, A.; Morello, M. J.; Moron, J.; Morris, A. -B.; Mountain, R.; Muheim, F.; Mueller, K.; Mussini, M.; Muster, B.; Naik, P.; Nakada, T.; Nandakumar, R.; Nasteva, I.; Needham, M.; Neri, N.; Neubert, S.; Neufeld, N.; Neuner, M.; Nguyen, A. D.; Nguyen, T. D.; Nguyen-Mau, C.; Nicol, M.; Niess, V.; Niet, R.; Nikitin, N.; Nikodem, T.; Novoselov, A.; O'Hanlon, D. P.; Oblakowska-Mucha, A.; Obraztsov, V.; Oggero, S.; Ogilvy, S.; Okhrimenko, O.; Oldeman, R.; Onderwater, G.; Orlandea, M.; Goicochea, J. M. Otalora; Owen, P.; Oyanguren, A.; Pal, B. K.; Palano, A.; Palombo, F.; Palutan, M.; Panman, J.; Papanestis, A.; Pappagallo, M.; Pappalardo, L. L.; Parkes, C.; Parkinson, C. J.; Passaleva, G.; Patel, G. D.; Patel, M.; Patrignani, C.; Alvarez, A. Pazos; Pearce, A.; Pellegrino, A.; Altarelli, M. Pepe; Perazzini, S.; Trigo, E. Perez; Perret, P.; Perrin-Terrin, M.; Pescatore, L.; Pesen, E.; Petridis, K.; Petrolini, A.; Olloqui, E. Picatoste; Pietrzyk, B.; Pilar, T.; Pinci, D.; Pistone, A.; Playfer, S.; Casasus, M. Plo; Polci, F.; Poluektov, A.; Polycarpo, E.; Popov, A.; Popov, D.; Popovici, B.; Potterat, C.; Price, E.; Price, J. D.; Prisciandaro, J.; Pritchard, A.; Prouve, C.; Pugatch, V.; Navarro, A. Puig; Punzi, G.; Qian, W.; Rachwal, B.; Rademacker, J. H.; Rakotomiaramanana, B.; Rama, M.; Rangel, M. S.; Raniuk, I.; Rauschmayr, N.; Raven, G.; Redi, F.; Reichert, S.; Reid, M. M.; dos Reis, A. C.; Ricciardi, S.; Richards, S.; Rihl, M.; Rinnert, K.; Molina, V. Rives; Robbe, P.; Rodrigues, A. B.; Rodrigues, E.; Perez, P. Rodriguez; Roiser, S.; Romanovsky, V.; Vidal, A. Romero; Rotondo, M.; Rouvinet, J.; Ruf, T.; Ruiz, H.; Valls, P. Ruiz; Silva, J. J. Saborido; Sagidova, N.; Sail, P.; Saitta, B.; Guimaraes, V. Salustino; Mayordomo, C. Sanchez; Sedes, B. Sanmartin; Santacesaria, R.; Rios, C. Santamarina; Santovetti, E.; Sarti, A.; Satriano, C.; Satta, A.; Saunders, D. M.; Savrie, M.; Savrina, D.; Schiller, M.; Schindler, H.; Schlupp, M.; Schmelling, M.; Schmidt, B.; Schneider, O.; Schopper, A.; Schune, M. -H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Seco, M.; Semennikov, A.; Sepp, I.; Serra, N.; Serrano, J.; Sestini, L.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, V.; Shires, A.; Coutinho, R. Silva; Simi, G.; Sirendi, M.; Skidmore, N.; Skwarnicki, T.; Smith, N. A.; Smith, E.; Smith, E.; Smith, J.; Smith, M.; Snoek, H.; Sokoloff, M. D.; Soler, F. J. P.; Soomro, F.; Souza, D.; De Paula, B. Souza; Spaan, B.; Sparkes, A.; Spradlin, P.; Sridharan, S.; Stagni, F.; Stah, M.; Stahl, S.; Steinkamp, O.; Stenyakin, O.; Stevenson, S.; Stoica, S.; Stone, S.; Storaci, B.; Stracka, S.; Straticiuc, M.; Straumann, U.; Stroili, R.; Subbiah, V. K.; Sun, L.; Sutcliffe, W.; Swientek, K.; Swientek, S.; Syropoulos, V.; Szczekowski, M.; Szczypka, P.; Szilard, D.; Szumlak, T.; T'Jampens, S.; Teklishyn, M.; Tellarini, G.; Teubert, F.; Thomas, C.; Thomas, E.; Vantilburg, J.; Tisserand, V.; Tobin, M.; Tolk, S.; Tomassetti, L.; Topp-Joergensen, S.; Torr, N.; Tournefier, E.; Tourneur, S.; Tran, M. T.; Tresch, M.; Tsaregorodtsev, A.; Tsopelas, P.; Tuning, N.; Garcia, M. Ubeda; Ukleja, A.; Ustyuzhanin, A.; Uwer, U.; Vacca, C.; Vagnoni, V.; Valenti, G.; Vallier, A.; Gomez, R. Vazquez; Regueiro, P. Vazquez; Sierra, C. Vazquez; Vecchi, S.; Velthuis, J. J.; Veltri, M.; Veneziano, G.; Vesterinen, M.; Viaud, B.; Vieira, D.; Diaz, M. Vieites; Vilasis-Cardona, X.; Vollhardt, A.; Volyanskyy, D.; Voong, D.; Vorobyev, A.; Vorobyev, V.; Voss, C.; Voss, H.; de Vries, J. A.; Waldi, R.; Wallace, C.; Wallace, R.; Walsh, J.; Wandernoth, S.; Wang, J.; Ward, D. R.; Watson, N. K.; Websdale, D.; Whitehead, M.; Wicht, J.; Wiedner, D.; Wilkinson, G.; Williams, M. P.; Williams, M.; Wilschut, H. W.; Wilson, F. F.; Wimberley, J.; Wishahi, J.; Wislicki, W.; Witek, M.; Wormser, G.; Wotton, S. A.; Wright, S.; Wyllie, K.; Xie, Y.; Xing, Z.; Xu, Z.; Yang, Z.; Yuan, X.; Yushchenko, O.; Zangoli, M.; Zavertyaev, M.; Zhang, L.; Zhang, W. C.; Zhang, Y.; Zhelezov, A.; Zhokhov, A.; Zhong, L.; Zvyagin, A.

    2015-01-01

    Using the latest LHCb measurements of time-dependent CP violation in the B-s(0) -> K+K- decay, a U-spin relation between the decay amplitudes of B-s(0) -> K+K- and B-0 -> p(+)p(-) decay processes allows constraints to be placed on the angle gamma of the unitarity triangle and on the B-s(0) mixing

  19. Separate assessment of natural beta and gamma dose-rates with TL from α-Al2O3:C single-crystal chips

    International Nuclear Information System (INIS)

    Kalchgruber, R.; Wagner, G.A.

    2006-01-01

    A measurement procedure was developed for fast and separate assessment of beta and gamma dose-rates in natural sediments using highly sensitive α-Al 2 O 3 :C single-crystal chips. The dosemeters were buried for periods from two days to three weeks in sediments with different layer structure and homogeneity. For each measurement, a pair of dosemeters was buried, in order to assess beta and gamma dose-rates separately. One dosemeter was wrapped only in thin plastic foil to shield it from alpha radiation, thus measuring beta + gamma components. The second one, used for the gamma component only, was packed additionally in a 1mm copper container for absorption of beta radiation. For calibration, another set of dosemeters was buried in reference soil with a well-known dose-rate and similar content of radioactive nuclides. By comparing the thermally stimulated luminescence signals from the dosemeters the gamma dose-rate and also, by subtraction, the beta dose-rate in the unknown soil could be determined. The calculated uncertainties were 5-7% and 10%, respectively. The resulting dose-rates for homogeneous and inhomogeneous media were compared with the results obtained by Ge- and on-site NaI-gamma-ray spectrometry. An agreement within 2σ-error limits was found for homogeneous media after only few days of exposure

  20. Endogenous PKI gamma limits the duration of the anti-apoptotic effects of PTH and beta-adrenergic agonists in osteoblasts.

    Science.gov (United States)

    Chen, Xin; Song, In-Hwan; Dennis, James E; Greenfield, Edward M

    2007-05-01

    PKI gamma knockdown substantially extended the anti-apoptotic effects of PTH and beta-adrenergic agonists, whereas PKI gamma overexpression decreased these effects. Therefore, inhibition of PKI gamma activity may provide a useful co-therapy in combination with intermittent PTH or beta-adrenergic agonists for bone loss in conditions such as osteoporosis. PTH has both catabolic and anabolic effects on bone, which are primarily caused by cAMP/protein kinase A (PKA) signaling and regulation of gene expression. We previously showed that protein kinase inhibitor-gamma (PKI gamma) is required for efficient termination of cAMP/PKA signaling and gene expression after stimulation with PTH or beta-adrenergic agonists. Inhibition of osteoblast apoptosis is thought to be an important, but transient, mechanism partly responsible for the anabolic effects of intermittent PTH. Therefore, we hypothesized that endogenous PKI gamma also terminates the anti-apoptotic effect of PTH. PKI gamma knockdown by antisense transfection or siRNA was used to examine the ability of endogenous PKI gamma to modulate the anti-apoptotic effects of PTH and beta-adrenergic agonists in ROS 17/2.8 cells. Knockdown of PKI gamma substantially extended the anti-apoptotic effects of PTH, whether apoptosis was induced by etoposide or dexamethasone. In contrast, overexpression of PKI gamma decreased the anti-apoptotic effect of PTH pretreatment. This study is also the first demonstration that beta-adrenergic agonists mimic the anti-apoptotic effects of PTH in osteoblasts. Moreover, PKI gamma knockdown also substantially extended this anti-apoptotic effect of beta-adrenergic agonists. Taken together, these results show that endogenous PKI gamma limits the duration of the anti-apoptotic effects of cAMP/PKA signaling in osteoblasts. Because significant individual variability exists in the anabolic responses to PTH therapy in current clinical treatment of osteoporosis, inhibition of PKI gamma activity may provide a

  1. Contribution to the study of {beta} disintegration and of nuclear structure using experiments on certain {beta}-{gamma} cascades: 198{sub Au}, 86{sub Rb}, 170{sub Tm}; Contribution a l'etude de la desintegration beta et a l'etude de la structure nucleaire a l'aide d'experiences sur certaines cascades beta-gamma: 198{sub Au}, 86{sub Rb}, 170{sub Tm}

    Energy Technology Data Exchange (ETDEWEB)

    Lachkar, J. [Commissariat a l' Energie Atomique, Bruyeres-le-Chatel (France). Centre d' Etudes; Paris-11 Univ., fabulte des Sciences 91 - Orsay (France)

    1969-07-01

    {beta}{gamma} directional angular correlations and shapes of inner beta spectra leading to the first excited level of the final nucleus enable one to determine the nuclear matrix elements typical of the {beta} transition. In the three observed first forbidden cases: {sup 170}Tm, {sup 86}Rb, {sup 198}Au, these matrix elements do not confirm the independent shell model theory. Other hypotheses are then suggested and discussed. (author) [French] Les experiences de correlation angulaire {beta}{gamma} et l'etude du spectre {beta} conduisant au premier niveau excite du noyau final permettent de determiner les elements de matrices nucleaires caracteristiques de cette transition. Dans les trois cas etudies (transitions une fois interdites): {sup 170}Tm, {sup 86}Rb, {sup 198}Au, ces elements de matrices ne peuvent etre retrouves a l'aide du modele en couches et a particules independantes. D'autres hypotheses sont alors emises et discutees. (auteur)

  2. Contribution to the study of {beta} disintegration and of nuclear structure using experiments on certain {beta}-{gamma} cascades: 198{sub Au}, 86{sub Rb}, 170{sub Tm}; Contribution a l'etude de la desintegration beta et a l'etude de la structure nucleaire a l'aide d'experiences sur certaines cascades beta-gamma: 198{sub Au}, 86{sub Rb}, 170{sub Tm}

    Energy Technology Data Exchange (ETDEWEB)

    Lachkar, J [Commissariat a l' Energie Atomique, Bruyeres-le-Chatel (France). Centre d' Etudes; Paris-11 Univ., fabulte des Sciences 91 - Orsay (France)

    1969-07-01

    {beta}{gamma} directional angular correlations and shapes of inner beta spectra leading to the first excited level of the final nucleus enable one to determine the nuclear matrix elements typical of the {beta} transition. In the three observed first forbidden cases: {sup 170}Tm, {sup 86}Rb, {sup 198}Au, these matrix elements do not confirm the independent shell model theory. Other hypotheses are then suggested and discussed. (author) [French] Les experiences de correlation angulaire {beta}{gamma} et l'etude du spectre {beta} conduisant au premier niveau excite du noyau final permettent de determiner les elements de matrices nucleaires caracteristiques de cette transition. Dans les trois cas etudies (transitions une fois interdites): {sup 170}Tm, {sup 86}Rb, {sup 198}Au, ces elements de matrices ne peuvent etre retrouves a l'aide du modele en couches et a particules independantes. D'autres hypotheses sont alors emises et discutees. (auteur)

  3. Study of radiation detectors response in standard X, gamma and beta radiation standard beams; Estudo da resposta de monitores de radioprotecao em feixes padronizados de radiacao X, gama e beta

    Energy Technology Data Exchange (ETDEWEB)

    Nonato, Fernanda Beatrice Conceicao

    2010-07-01

    The response of 76 Geiger-Mueller detectors, 4 semiconductor detectors and 34 ionization chambers were studied. Many of them were calibrated with gamma radiation beams ({sup 37}Cs and {sup 60}Co), and some of them were tested in beta radiation ({sup 90}Sr+{sup 9'}0Y e {sup 204}Tl) and X radiation (N-60, N-80, N-100, N-150) beams. For all three types of radiation, the calibration factors of the instruments were obtained, and the energy and angular dependences were studied. For beta and gamma radiation, the angular dependence was studied for incident radiation angles of 0 deg and +- 45 deg. The curves of the response of the instruments were obtained over an angle interval of 0 deg to +- 90 deg, for gamma, beta and X radiations. The calibration factors obtained for beta radiation were compared to those obtained for gamma radiation. For gamma radiation, 24 of the 66 tested Geiger-Mueller detectors presented results for the energy dependence according to international recommendation of ISO 4037-2 and 56 were in accordance with the Brazilian ABNT 10011 recommendation. The ionization chambers and semiconductors were in accordance to national and international recommendations. All instruments showed angular dependence less than 40%. For beta radiation, the instruments showed unsatisfactory results for the energy dependence and angular dependence. For X radiation, the ionization chambers presented results for energy dependence according to the national recommendation, and the angular dependence was less than 40%. (author)

  4. Study of radiation detectors response in standard X, gamma and beta radiation standard beams; Estudo da resposta de monitores de radioprotecao em feixes padronizados de radiacao X, gama e beta

    Energy Technology Data Exchange (ETDEWEB)

    Nonato, Fernanda Beatrice Conceicao

    2010-07-01

    The response of 76 Geiger-Mueller detectors, 4 semiconductor detectors and 34 ionization chambers were studied. Many of them were calibrated with gamma radiation beams ({sup 37}Cs and {sup 60}Co), and some of them were tested in beta radiation ({sup 90}Sr+{sup 9'}0Y e {sup 204}Tl) and X radiation (N-60, N-80, N-100, N-150) beams. For all three types of radiation, the calibration factors of the instruments were obtained, and the energy and angular dependences were studied. For beta and gamma radiation, the angular dependence was studied for incident radiation angles of 0 deg and +- 45 deg. The curves of the response of the instruments were obtained over an angle interval of 0 deg to +- 90 deg, for gamma, beta and X radiations. The calibration factors obtained for beta radiation were compared to those obtained for gamma radiation. For gamma radiation, 24 of the 66 tested Geiger-Mueller detectors presented results for the energy dependence according to international recommendation of ISO 4037-2 and 56 were in accordance with the Brazilian ABNT 10011 recommendation. The ionization chambers and semiconductors were in accordance to national and international recommendations. All instruments showed angular dependence less than 40%. For beta radiation, the instruments showed unsatisfactory results for the energy dependence and angular dependence. For X radiation, the ionization chambers presented results for energy dependence according to the national recommendation, and the angular dependence was less than 40%. (author)

  5. Thermoluminescent characterization of thin films of aluminium oxide submitted to beta and gamma radiation; Caracterizacion termoluminiscente de peliculas delgadas de oxido de aluminio sometidas a radiacion beta y gamma

    Energy Technology Data Exchange (ETDEWEB)

    Villagran, E.; Escobar A, L.; Camps, E.; Gonzalez, P.R.; Martinez A, L. [Instituto Nacional de Investigaciones Nucleares, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    2002-07-01

    By mean of the laser ablation technique, thin films of aluminium oxide have been deposited on kapton substrates. These films present thermoluminescent response (Tl) when they are exposed to beta and gamma radiation. The brilliance curves show two peaks between 112 C and 180 C. A dose-response relationship study was realized and the Tl kinetic parameters were determined using the computerized deconvolution of the brilliance curve (CGCD). The thin films of aluminium oxide have potential applications as ultra.thin radiation dosemeters. (Author)

  6. Circadian rhythms, Wnt/beta-catenin pathway and PPAR alpha/gamma profiles in diseases with primary or secondary cardiac dysfunction

    Directory of Open Access Journals (Sweden)

    Yves eLecarpentier

    2014-11-01

    Full Text Available Circadian clock mechanisms are far-from-equilibrium dissipative structures. Peroxisome proliferator-activated receptors (PPAR alpha, beta/delta and gamma play a key role in metabolic regulatory processes, particularly in heart muscle. Links between circadian rhythms (CRs and PPARs have been established. Mammalian CRs involve at least two critical transcription factors, CLOCK and BMAL1 (Gekakis et al., 1998; Hogenesch et al., 1998. PPAR gamma plays a major role in both glucose and lipid metabolisms and presents circadian properties which coordinate the interplay between metabolism and CRs. PPAR gamma is a major component of the vascular clock. Vascular PPAR gamma is a peripheral regulator of cardiovascular rhythms controlling circadian variations in blood pressure and heart rate through BMAL1. We focused our review on diseases with abnormalities of CRs and with primary or secondary cardiac dysfunction. Moreover, these diseases presented changes in the Wnt/beta-catenin pathway and PPARs, according to two opposed profiles. Profile 1 was defined as follows: inactivation of the Wnt/beta-catenin pathway with increased expression of PPAR gamma. Profile 2 was defined as follows: activation of the Wnt/beta-catenin pathway with decreased expression of PPAR gamma. A typical profile 1 disease is arrhythmogenic right ventricular cardiomyopathy, a genetic cardiac disease which presents mutations of the desmosomal proteins and is mainly characterized by fatty acid accumulation in adult cardiomyocytes mainly in the right ventricle. The link between PPAR gamma dysfunction and desmosomal genetic mutations occurs via inactivation of the Wnt/beta-catenin pathway presenting oscillatory properties. A typical profile 2 disease is type 2 diabetes, with activation of the Wnt/beta-catenin pathway and decreased expression of PPAR gamma. CRs abnormalities are present in numerous pathologies such as cardiovascular diseases, sympathetic/parasympathetic dysfunction

  7. Evaluation of immune responses in HIV infected patients with pleural tuberculosis by the QuantiFERON® TB-Gold interferon-gamma assay

    Directory of Open Access Journals (Sweden)

    Lekabe Jacob M

    2008-03-01

    Full Text Available Abstract Background Diagnosis of tuberculous (TB pleuritis is difficult and better diagnostic tools are needed. New blood based interferon-gamma (IFN-γ tests are promising, but sensitivity could be low in HIV positive patients. The IFN-γ tests have not yet been validated for use in pleural fluid, a compartment with higher level of immune activation than in blood. Methods The QuantiFERON TB®-Gold (QFT-TB test was analysed in blood and pleural fluid from 34 patients presenting with clinically suspected pleural TB. Clinical data, HIV status and CD4 cell counts were recorded. Adenosine deaminase activity (ADA analysis and TB culture were performed on pleural fluid. Results The patients were categorised as 'confirmed TB' (n = 12, 'probable TB' (n = 16 and 'non-TB' pleuritis (n = 6 based on TB culture results and clinical and biochemical criteria. The majority of the TB patients were HIV infected (82%. The QFT-TB in pleural fluid was positive in 27% and 56% of the 'confirmed TB' and 'probable TB' cases, respectively, whereas the corresponding sensitivities in blood were 58% and 83%. Indeterminate results in blood (25% were caused by low phytohemagglutinin (PHA = positive control IFN-γ responses, significantly lower in the TB patients as compared to the 'non-TB' cases (p = 0.02. Blood PHA responses correlated with CD4 cell count (r = 0.600, p = 0.028. In contrast, in pleural fluid indeterminate results (52% were caused by high Nil (negative control IFN-γ responses in both TB groups. Still, the Nil IFN-γ responses were lower than the TB antigen responses (p Conclusion The QFT-TB test in blood could contribute to the diagnosis of TB pleuritis in the HIV positive population. Still, the number of inconclusive results is too high to recommend the commercial QFT-TB test for routine use in pleural fluid in a TB/HIV endemic resource-limited setting.

  8. A highly sensitive label-free electrochemical aptasensor for interferon-gamma detection based on graphene controlled assembly and nuclease cleavage-assisted target recycling amplification.

    Science.gov (United States)

    Yan, Genping; Wang, Yonghong; He, Xiaoxiao; Wang, Kemin; Liu, Jinquan; Du, Yudan

    2013-06-15

    We report here a highly sensitive and label-free electrochemical aptasensing technology for detection of interferon-gamma (IFN-γ) based on graphene controlled assembly and enzyme cleavage-assisted target recycling amplification strategy. In this work, in the absence of IFN-γ, the graphene could not be assembled onto the 16-mercaptohexadecanoic acid (MHA) modified gold electrode because the IFN-γ binding aptamer was strongly adsorbed on the graphene due to the strong π-π interaction. Thus the electronic transmission was blocked (eT OFF). However, the presence of target IFN-γ and DNase I led to desorption of aptamer from the graphene surface and further cleavage of the aptamer, thereby releasing the IFN-γ. The released IFN-γ could then re-attack other aptamers on the graphene, resulting in the successive release of the aptamers from the graphene. At the same time, the "naked" graphene could be assembled onto the MHA modified gold electrode with hydrophobic interaction and π-conjunction, mediating the electron transfer between the electrode and the electroactive indicator. Then, measurable electrochemical signals were generated (eT ON), which was related to the concentration of the IFN-γ. By taking advantages of graphene and enzyme cleavage-assisted target recycling amplification, the developed label-free electrochemical aptasensing technology showed a linear response to concentration of IFN-γ range from 0.1 to 0.7 pM. The detection limit of IFN-γ was determined to be 0.065 pM. Moreover, this aptasensor shows good selectivity toward the target in the presence of other relevant proteins. Our strategy thus opens new opportunities for label-free and amplified detection of other kinds of proteins. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Sphingosine kinase inhibitor suppresses IL-18-induced interferon-gamma production through inhibition of p38 MAPK activation in human NK cells

    International Nuclear Information System (INIS)

    Cheon, Soyoung; Song, Seok Bean; Jung, Minkyung; Park, Yoorim; Bang, Jung-Wook; Kim, Tae Sung; Park, Hyunjeong; Kim, Cherl-hyun; Yang, Yool-hee; Bang, Sa Ik; Cho, Daeho

    2008-01-01

    Natural killer (NK) cells play an important role in the innate immune response. Interleukin-18 (IL-18) is a well-known interferon-gamma (IFN-γ inducing factor, which stimulates immune response in NK and T cells. Sphingosine kinase (SPHK) catalyzes the formation of sphingosine 1-phosphate (S1P), which acts as a second messenger to function as an anti-apoptotic factor and proliferation stimulator of immune cells. In this study, to elucidate whether SPHK is involved in IL-18-induced IFN-γ production, we measured IL-18-induced IFN-γ production after pre-treatment with SPHK inhibitor (SKI) in NK-92MI cells. We found that IL-18-induced IFN-γ expression was blocked by SKI pre-treatment in both mRNA and protein levels. In addition, the increased IFN-γ production by stimulation with IL-18 is mediated through both SPHK and p38 MAPK. To determine the upstream signals of SKI and p38 MAPK in IL-18-induced IFN-γ production, phosphorylation levels of p38 MAPK was measured after SKI pre-treatment. As a result, inhibition of SPHK by SKI blocked phosphorylation of p38 MAPK, showing that SPHK activation by IL-18 is an upstream signal of p38 MAPK activation. Inhibition of SPHK by SKI also inhibited IL-18-induced IFN-γ production in human primary NK cells. In conclusion, SPHK activation is an essential factor for IL-18-induced IFN-γ production via p38 MAPK

  10. ROS mediates interferon gamma induced phosphorylation of Src, through the Raf/ERK pathway, in MCF-7 human breast cancer cell line.

    Science.gov (United States)

    Zibara, Kazem; Zeidan, Asad; Bjeije, Hassan; Kassem, Nouhad; Badran, Bassam; El-Zein, Nabil

    2017-03-01

    Interferon gamma (IFN-ɣ) is a pleiotropic cytokine which plays dual contrasting roles in cancer. Although IFN-ɣ has been clinically used to treat various malignancies, it was recently shown to have protumorigenic activities. Reactive oxygen species (ROS) are overproduced in cancer cells, mainly due to NADPH oxidase activity, which results into several changes in signaling pathways. In this study, we examined IFN-ɣ effect on the phosphorylation levels of key signaling proteins, through ROS production, in the human breast cancer cell line MCF-7. After treatment by IFN-ɣ, results showed a significant increase in the phosphorylation of STAT1, Src, raf, AKT, ERK1/2 and p38 signaling molecules, in a time specific manner. Src and Raf were found to be involved in early stages of IFN-ɣ signaling since their phosphorylation increased very rapidly. Selective inhibition of Src-family kinases resulted in an immediate significant decrease in the phosphorylation status of Raf and ERK1/2, but not p38 and AKT. On the other hand, IFN-ɣ resulted in ROS generation, through H 2 O 2 production, whereas pre-treatment with the ROS inhibitor NAC caused ROS inhibition and a significant decrease in the phosphorylation levels of AKT, ERK1/2, p38 and STAT1. Moreover, pretreatment with a selective NOX1 inhibitor resulted in a significant decrease of AKT phosphorylation. Finally, no direct relationship was found between ROS production and calcium mobilization. In summary, IFN-ɣ signaling in MCF-7 cell line is ROS-dependent and follows the Src/Raf/ERK pathway whereas its signaling through the AKT pathway is highly dependent on NOX1.

  11. Cross-talk between IGF-1 and estrogen receptors attenuates intracellular changes in ventral spinal cord 4.1 motoneuron cells due to interferon-gamma exposure

    Science.gov (United States)

    Park, Sookyoung; Nozaki, Kenkichi; Smith, Joshua A.; Krause, James S.; Banik, Naren L.

    2014-01-01

    Insulin-like growth factor-1 (IGF-1) is a neuroprotective growth factor that promotes neuronal survival by inhibition of apoptosis. In order to examine whether IGF-1 exerts cytoprotective effects against extracellular inflammatory stimulation, ventral spinal cord 4.1 (VSC4.1) motoneuron cells were treated with interferon-gamma (IFN-γ). Our data demonstrated apoptotic changes, increased calpain:calpastatin and Bax:Bcl-2 ratios, and expression of apoptosis related proteases (caspase-3 and −12) in motoneurons rendered by IFN-γ in a dose-dependent manner. Post-treatment with IGF-1 attenuated these changes. In addition, IGF-1 treatment of motoneurons exposed to IFN-γ decreased expression of inflammatory markers (cyclooxygenase-2 and nuclear factor-kappa B:inhibitor of kappa B ratio). Furthermore, IGF-1 attenuated the loss of expression of IGF-1 receptors (IGF-1Rα and IGF-1Rβ) and estrogen receptors (ERα and ERβ) induced by IFN-γ. To determine whether the protective effects of IGF-1 are associated with ERs, ERs antagonist ICI and selective siRNA targeted against ERα and ERβ were used in VSC4.1 motoneurons. Distinctive morphological changes were observed following siRNA knockdown of ERα and ERβ. In particular, apoptotic cell death assessed by TUNEL assay was enhanced in both ERα and ERβ-silenced VSC4.1 motoneurons following IFN-γ and IGF-1 exposure. These results suggest that IGF-1 protects motoneurons from inflammatory insult by a mechanism involving pivotal interactions with ERα and ERβ. PMID:24188094

  12. Cross-talk between IGF-1 and estrogen receptors attenuates intracellular changes in ventral spinal cord 4.1 motoneuron cells because of interferon-gamma exposure.

    Science.gov (United States)

    Park, Sookyoung; Nozaki, Kenkichi; Smith, Joshua A; Krause, James S; Banik, Naren L

    2014-03-01

    Insulin-like growth factor-1 (IGF-1) is a neuroprotective growth factor that promotes neuronal survival by inhibition of apoptosis. To examine whether IGF-1 exerts cytoprotective effects against extracellular inflammatory stimulation, ventral spinal cord 4.1 (VSC4.1) motoneuron cells were treated with interferon-gamma (IFN-γ). Our data demonstrated apoptotic changes, increased calpain:calpastatin and Bax:Bcl-2 ratios, and expression of apoptosis-related proteases (caspase-3 and -12) in motoneurons rendered by IFN-γ in a dose-dependent manner. Post-treatment with IGF-1 attenuated these changes. In addition, IGF-1 treatment of motoneurons exposed to IFN-γ decreased expression of inflammatory markers (cyclooxygenase-2 and nuclear factor-kappa B:inhibitor of kappa B ratio). Furthermore, IGF-1 attenuated the loss of expression of IGF-1 receptors (IGF-1Rα and IGF-1Rβ) and estrogen receptors (ERα and ERβ) induced by IFN-γ. To determine whether the protective effects of IGF-1 are associated with ERs, ERs antagonist ICI and selective siRNA targeted against ERα and ERβ were used in VSC4.1 motoneurons. Distinctive morphological changes were observed following siRNA knockdown of ERα and ERβ. In particular, apoptotic cell death assessed by TUNEL assay was enhanced in both ERα and ERβ-silenced VSC4.1 motoneurons following IFN-γ and IGF-1 exposure. These results suggest that IGF-1 protects motoneurons from inflammatory insult by a mechanism involving pivotal interactions with ERα and ERβ. © 2013 International Society for Neurochemistry.

  13. Screening of latent tuberculosis infection among health care workers working in Hajj pilgrimage area in Saudi Arabia, using interferon gamma release assay and tuberculin skin test.

    Science.gov (United States)

    Bukhary, Zakeya A; Amer, Soliman M; Emara, Magdy M; Abdalla, Mohammad E; Ali, Sahar A

    2018-01-01

    Interferon gamma release assays (IGRA) is highly specific for Mycobacterium tuberculosis and is the preferred test in BCG-vaccinated individuals. The few studies that have screened health care workers (HCWs) in Saudi Arabia for latent tuberculosis infection (LTBI) using IGRA have varied in agreement with the traditional tuberculin skin test (TST). Assess the prevalence of LTBI among HCWs working in the Hajj pilgrimage using IGRA and TST and measuring their agreement. Cross-sectional prospective. Multiple non-tertiary care hospitals. HCWs who worked during the Hajj pilgrimage in Saudi Arabia in December 2015. Data was collected by standarized questionnaire. Samples were drawn and analyzed by standard methods. The prevalence of LTBI among HCW and the agreement by kappa statistic between QFT-GIT and TST. 520 subjects. Nurses accounted for 30.7% of the sample and physicians, 19.2%. The majority were BCG vaccinated (98.5%). There were a total of 56 positive by QFT-GIT and the LTBI rate was 10.8%. In 50 QFT positive/476 TST negative the LTBI rate was 10.5% in discordant tests, and in 6 QFT positive/44 TST positive it was 13.6% in concordant tests. The overall agreement between both tests was poor-83% and kappa was 0.02. LTBI prevalence was associated with longer employment (13.1 [9.2] years). The QFT-GIT positive test was significantly higher in physicians (P=.02) and in HCWs working in chest hospitals 16/76 (21.05%) (P=.001). Agreement between the tests was poor. QFT-GIT detected LTBI when TST was negative in HCWs who had a history of close contact with TB patients. A second step TST was not feasible within 2-3 weeks. None.

  14. Comparison of interferon {gamma} release assays and conventional screening tests before tumour necrosis factor {alpha} blockade in patients with inflammatory arthritis.

    LENUS (Irish Health Repository)

    Martin, J

    2012-02-01

    OBJECTIVE: To compare the performance of two interferon gamma release assays (IGRAs) and conventional screening tests in patients with inflammatory arthritis undergoing screening for latent tuberculosis infection (LTBI) before treatment with anti-tumour necrosis factor alpha (anti-TNFalpha) compounds. METHODS: Successive patients were subjected to conventional LTBI screening, including a tuberculin skin test (TST). The T-SPOT.TB test was performed on all patients and the QuantiFERON-TB Gold test was performed on a large subset. The results of the IGRAs were compared with the results of conventional screening tests. RESULTS: A total 150 patients were evaluated. The majority (57.9%) had rheumatoid arthritis. Previous vaccination with Bacille Calmette-Guerin was confirmed in 82% of patients. No patient had received prior anti-TB treatment. A total of 57 patients (38.0%) had at least one positive conventional risk factor. In contrast, an unequivocally positive T-SPOT.TB test was seen in only 14\\/143 (9.8%). There was 98.2% agreement between the two IGRAs. Statistically significant associations were found between each of the IGRAs and both TST and risk history, but not chest x-ray (CXR). A positive IGRA result was significantly associated with increased age. TB was not reactivated in any patient during the follow-up period. Interpretation: This study suggests that IGRAs may be useful when screening for LTBI before anti-TNFalpha therapy in patients with immune-mediated inflammatory diseases. The observations reported here also highlight the inadequate performance of CXR as a marker of LTBI.

  15. Regulation of CD95 expression and CD95-mediated cell death by interferon-gamma in acute lymphoblastic leukemia with chromosomal translocation t(4;11).

    Science.gov (United States)

    Dörrie, J; Schuh, W; Keil, A; Bongards, E; Greil, J; Fey, G H; Zunino, S J

    1999-10-01

    The regulatory effects of IFNgamma on CD95 expression and CD95-mediated cell death were investigated in three high-risk pro-B acute lymphoblastic leukemia (ALL) lines that carry the chromosomal translocation t(4;11)(q21;q23). These leukemias are characteristically refractory to conventional chemotherapeutic treatments operating through the induction of apoptosis. However, the mechanisms leading to increased cell survival and resistance to cell death in these leukemias are largely unknown. Interferon-gamma (IFNgamma), a potent inhibitor of hematopoiesis, acts in part by upregulating CD95 and sensitizing cells to CD95-induced apoptosis. The t(4;11) lines SEM, RS4;11, and MV4;11 expressed low levels of CD95, but were completely resistant to CD95-mediated death. Addition of IFNgamma markedly upregulated CD95 expression in SEM (8-9-fold), RS4;11 (2-3-fold), and MV4;11 (2-3-fold) lines. However, after treatment with IFNgamma, only an 11% increase in sensitivity to CD95-mediated cell death was observed in SEM cells, whereas RS4;11 and MV4;11 cells remained resistant. Cycloheximide, but not actinomycin D or brefeldin A, increased CD95-specific cell death only in IFNgamma-treated RS4;11 cells by approximately 12%. Abundant levels of Bcl-2 and Bcl-XL, known to inhibit CD95-signaling in some cells, were present suggesting a possible role for both molecules in the resistance to CD95-mediated cell death. Resistance of the leukemic blasts to CD95-mediated cell death and the failure of IFNgamma to substantially sensitize the CD95-signaling pathway may contribute to the highly malignant phenotype of pro-B ALL with translocation t(4;11).

  16. Enhanced expression in vivo of HLA-ABC antigens and beta 2-microglobulin on human lymphoid cells induced by human interferon-alpha in patients with lung cancer. Enhanced expression of class I major histocompatibility antigens prior to treatment

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Plesner, T; Larsen, J K

    1985-01-01

    than 0.5, respectively) by day-to-day analysis of an untreated healthy control group. An increased expression of both HLA-ABC (mean 55%, P less than 0.0005) and beta 2m (mean 23%, P less than 0.01) was also observed prior to treatment in the lung cancer patients when compared to a group of age matched......The effect of cloned human interferon-alpha (IFN-alpha) on the expression of HLA-ABC antigens (HLA-ABC) and beta 2-microglobulin (beta 2m) on human peripheral lymphoid cells in vivo was studied by cytofluorometry using monoclonal antibodies and fluorescein-labelled rabbit anti-mouse immunoglobulin....... A significant increase in the mean fluorescence intensity of HLA-ABC (median 59%, P less than 0.001) and beta 2m (median 57%, P less than 0.001) on small lymphoid cells was observed 24 h after initiation of IFN-alpha treatment (50 X 10(6) units IFN-alpha/m2 three times a week). The enhanced expression...

  17. Low-level multicounter {beta}/{gamma} systems with external guards in surface and shallow underground laboratories

    Energy Technology Data Exchange (ETDEWEB)

    Theodorsson, P [Iceland Univ. (Iceland). Science Inst.

    1997-03-01

    When weak samples are measured it is important that they can be given ample counting time in order to obtain satisfactory accuracy and that the background count rate can be checked well. This calls for a high counting capacity, which multidetectors can bring us. I will discuss development possibilities of low-level {beta}/{gamma} multidetector systems with an external anticosmic shield that will in many cases be operated in underground laboratories. These simple and low-cost system can frequently help us in increasing the number of detectors. Three concepts are combined in these systems: (1) multidetectors, (2) an external anticosmic (or guard) detector arrangement and (3) overburden shielding. (orig.)

  18. Influence of heat treatment in {beta} and {gamma} phases on the microscopic structure of uranium; Influence des traitements thermiques en phases {beta} et {gamma} sur la structure micrographique de l'uranium

    Energy Technology Data Exchange (ETDEWEB)

    Robillard, A

    1958-06-02

    A new method of microscopic examination of uranium is described. Electrolytic polishing and etching are carried out in an acetic acid-chromic acid bath. Atmospheric or anodic oxidation of the polished surface produces films which follow exactly changes in the structure of the underlying metal. This method is very sensitive to small variations of orientation in polygonized crystals. Using this method of examination of uranium, it was found that annealing U in the {gamma} phase followed by a cooling at a rate dependent of the annealing temperature, causes the formation of substructures different from those due to the polygonization of {alpha}-U. The substructures are indicated by the concentration of impurities on the dislocations induced by the stresses accompanying the allotropic transformation {gamma} {yields} {beta}. Similar treatment of the U-1.4% Cr alloy in which the {beta} phase is stabilized at room temperature, confirms this explanation. In addition to the polygonization substructures, sharp discontinuities can be observed in the network of sub- boundaries as a fine white edging. The comparison of these with the structure revealed by thermal etching in vacuum suggest that there are traces of the grain boundaries of the {gamma} phase. The method of etching followed by oxidation shows a haloed phase identified as UH{sub 3}. The conditions of appearance and disappearance of this phase are studied. The sensitivity of this method of detecting the last traces of H in U is very high. The dependence of the hydrogen content on the tensile properties of uranium metal was also studied. (author) [French] Une methode nouvelle d'examen micrographique de l'uranium a ete mise au point. Le polissage electrolytique et le 'gravage' sont effectues dans un bain acide acetique-acide chromique. L'oxydation atmospherique ou anodique de la surface polie conduit a la formation de couches epitaxiques d'oxyde. Cette methode est particulierement sensible aux faibles variations d

  19. Influence of heat treatment in {beta} and {gamma} phases on the microscopic structure of uranium; Influence des traitements thermiques en phases {beta} et {gamma} sur la structure micrographique de l'uranium

    Energy Technology Data Exchange (ETDEWEB)

    Robillard, A

    1958-06-02

    A new method of microscopic examination of uranium is described. Electrolytic polishing and etching are carried out in an acetic acid-chromic acid bath. Atmospheric or anodic oxidation of the polished surface produces films which follow exactly changes in the structure of the underlying metal. This method is very sensitive to small variations of orientation in polygonized crystals. Using this method of examination of uranium, it was found that annealing U in the {gamma} phase followed by a cooling at a rate dependent of the annealing temperature, causes the formation of substructures different from those due to the polygonization of {alpha}-U. The substructures are indicated by the concentration of impurities on the dislocations induced by the stresses accompanying the allotropic transformation {gamma} {yields} {beta}. Similar treatment of the U-1.4% Cr alloy in which the {beta} phase is stabilized at room temperature, confirms this explanation. In addition to the polygonization substructures, sharp discontinuities can be observed in the network of sub- boundaries as a fine white edging. The comparison of these with the structure revealed by thermal etching in vacuum suggest that there are traces of the grain boundaries of the {gamma} phase. The method of etching followed by oxidation shows a haloed phase identified as UH{sub 3}. The conditions of appearance and disappearance of this phase are studied. The sensitivity of this method of detecting the last traces of H in U is very high. The dependence of the hydrogen content on the tensile properties of uranium metal was also studied. (author) [French] Une methode nouvelle d'examen micrographique de l'uranium a ete mise au point. Le polissage electrolytique et le 'gravage' sont effectues dans un bain acide acetique-acide chromique. L'oxydation atmospherique ou anodique de la surface polie conduit a la formation de couches epitaxiques d'oxyde. Cette methode est particulierement sensible

  20. Clinical practice of analysis of anti-drug antibodies against interferon beta and natalizumab in multiple sclerosis patients in Europe: A descriptive study of test results.

    Directory of Open Access Journals (Sweden)

    Jenny Link

    Full Text Available Antibodies against biopharmaceuticals (anti-drug antibodies, ADA have been a well-integrated part of the clinical care of multiple sclerosis (MS in several European countries. ADA data generated in Europe during the more than 10 years of ADA monitoring in MS patients treated with interferon beta (IFNβ and natalizumab have been pooled and characterized through collaboration within a European consortium. The aim of this study was to report on the clinical practice of ADA testing in Europe, considering the number of ADA tests performed and type of ADA assays used, and to determine the frequency of ADA testing against the different drug preparations in different countries. A common database platform (tranSMART for querying, analyzing and storing retrospective data of MS cohorts was set up to harmonize the data and compare results of ADA tests between different countries. Retrospective data from six countries (Sweden, Austria, Spain, Switzerland, Germany and Denmark on 20,695 patients and on 42,555 samples were loaded into tranSMART including data points of age, gender, treatment, samples, and ADA results. The previously observed immunogenic difference among the four IFNβ preparations was confirmed in this large dataset. Decreased usage of the more immunogenic preparations IFNβ-1a subcutaneous (s.c. and IFNβ-1b s.c. in favor of the least immunogenic preparation IFNβ-1a intramuscular (i.m. was observed. The median time from treatment start to first ADA test correlated with time to first positive test. Shorter times were observed for IFNβ-1b-Extavia s.c. (0.99 and 0.94 years and natalizumab (0.25 and 0.23 years, which were introduced on the market when ADA testing was already available, as compared to IFNβ-1a i.m. (1.41 and 2.27 years, IFNβ-1b-Betaferon s.c. (2.51 and 1.96 years and IFNβ-1a s.c. (2.11 and 2.09 years which were available years before routine testing began. A higher rate of anti-IFNβ ADA was observed in test samples taken from

  1. Electronic, optical and transport properties of {alpha}-, {beta}- and {gamma}-phases of spinel indium sulphide: An ab initio study

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Yamini, E-mail: sharma.yamini62@gmail.com [Department of Physics, Feroze Gandhi College, Rae Bareli 229001, U.P. (India); Srivastava, Pankaj [Department of Physics, Feroze Gandhi College, Rae Bareli 229001, U.P. (India)

    2012-08-15

    Spinel indium sulphide exists in three phases. The tetragonal {beta}-phase transforms to the cubic {alpha}-phase at 420 Degree-Sign C which further transforms to the trigonal {gamma}-phase at 754 Degree-Sign C. Due to wide energy bandgap, the phases of indium sulphide have possibilities of applications in photo-electrochemical solar cell devices as a replacement of toxic CdS. The electronic, optical and transport properties of the three phases have therefore been investigated using full potential linear augmented plane wave (FP-LAPW) + local orbitals (lo) scheme, in the framework of density functional theory (DFT) with generalized gradient approximation (GGA) for the purpose of exchange-correlation energy functional. We present the structure, energy bands and density of states (DOS) for {alpha}-, {beta}- and {gamma}-phases. The partial density of states (PDOS) of {beta}-In{sub 2}S{sub 3} is in good agreement with experiment and earlier ab initio calculations. To obtain the fundamental characteristics of these phases we have analysed their linear optical properties such as the dynamic dielectric function in the energy range of 0-15 eV. From the dynamic dielectric function it is seen that there is no directional anisotropy for {alpha}-phase since the longitudinal and transverse components are almost identical, however the {beta} and {gamma}-phases show birefringence. The optical absorption profiles clearly indicate that {beta}-phase has possibility of greater multiple direct and indirect interband transitions in the visible regions compared to the other phases. To study the existence of interesting thermoelectric properties, transport properties like electrical and thermal conductivities, Seebeck and Hall coefficients etc. are also calculated. Good agreements are found with the available experimental results. -- Highlights: Black-Right-Pointing-Pointer The electronic properties of phases of In{sub 2}S{sub 3} have been investigated. Black-Right-Pointing-Pointer The

  2. Patient subgroup analyses of the treatment effect of subcutaneous interferon beta-1a on development of multiple sclerosis in the randomized controlled REFLEX study

    NARCIS (Netherlands)

    Freedman, M.S.; De Stefano, N.; Barkhof, F.; Polman, C.H.; Comi, G.; Uitdehaag, B.M.J.; Casset-Semanaz, F.; Hennessy, B.; Lehr, L.; Stubinski, B.; Jack, D.L.; Kappos, L.

    2014-01-01

    The REFLEX study (NCT00404352) established that subcutaneous (sc) interferon (IFN) β-1a reduced the risks of McDonald MS (2005 criteria) and clinically definite multiple sclerosis (CDMS) in patients with a first clinical demyelinating event suggestive of MS. The aim of this subgroup analysis was to

  3. Principles of medical rehabilitation of survivors of acute radiation sickness induced by gamma and beta and gumma and neutron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Nedejina, N.M.; Galstian, I.A.; Savitsky, A.A.; Sachkov, A.V.; Rtisheva, J.N.; Uvatcheva, I.V.; Filin, S.V. [State Research Center of Russia, Moscow (Russian Federation). Inst. of Biophysics

    2000-05-01

    The purpose of this study is to reveal the principles of medical rehabilitation different degree acute radiation syndrome (ARS) survivors, who exposed {gamma}{beta}- and {gamma}{eta}-irradiation in different radiation accidents. The main reasons of working disability in the late consequences of ARS period are consequences of local radiation injures (LRI) and joining somatic diseases. Its revealing and treatment considerably improves quality of life of the patients. The heaviest consequence of LRI of a skin at {gamma}{beta}- radiation exposure is the development of late radiation ulcers and radiation fibrosis, which require repeated plastic surgery. LRI at {gamma}{eta}-radiation exposure differ by the greater depth of destruction of a underlying tissues and similar defects require the early amputations. Last 10 years microsurgery methods of plastic surgery allow to save more large segments of extremities and to decrease expression of the late consequences (radiation fibrosis and late radiation ulcers) LRI severe and extremely severe degrees. Medical rehabilitation of radiation cataract (development at doses more than 2.0 Gy) includes its extraction and artificial lens implantation, if acuity of vision is considerably decreased. Changes of peripheral blood, observed at the period of the long consequences, as a rule, different, moderate, transient and not requiring treatment. Only one ARS survivor dead from chronic myeloid leukemia. Thyroid nodes, not requiring operative intervention, are found out in Chernobyl survivors. Within the time course the concurrent somatic disease become the major importance for patients disability growth, which concurrent diseases seem to be unrelated to radiation dose and their structure does not differ from that found in general public of Russia. The rehabilitation of the persons who have transferred ARS as a result of radiating failure, should be directed on restoration of functions critical for ionizing of radiation of bodies and

  4. Lightweight High Temperature Beta Gamma Alloy/Process Development for Disk and Blade Applications, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The primary material and manufacturing limitations of gamma TiAl alloys include processing difficulties, requiring costly non-conventional processing requirements,...

  5. Study of a 4{pi}{beta}-{gamma} coincidence system for absolute radionuclide activity measurement using plastic scintillators; Estudo de um sistema de coincidencias 4{pi}{beta}-{gamma} para a medida absoluta de atividade de radionuclideos empregando cintiladores plasticos

    Energy Technology Data Exchange (ETDEWEB)

    Piuvezam Filho, Helio

    2007-07-01

    The present work was intended to study a coincidence system 4{pi}(PS){beta}-{gamma} for absolute activity measurement using plastic scintillators in 4{pi} geometry. Along with experiments on the coincidence system, simulations were also performed applying the Monte Carlo Method, by means of codes PENELOPE and ESQUEMA. These simulations were performed in order to calculate the extrapolation curve of the coincidence system 4{pi}(PS){beta}-{gamma} and compare it to experimental data. A new geometry was proposed to the coincidence system adding up a second photomultiplier tube to the previous system for improving light collection from the plastic scintillator, as this system presented limitations in the minimum detected energy due to the presence of electronic noise and low gain. The results show that an improvement in the signal-to-noise ratio was obtained, as well as in the minimum detected energy. Moreover, there was an increase in the detection efficiency. With these modifications, it is now possible to calibrate radionuclides which emit low energy electrons or X-rays, increasing the number of radionuclides that can be standardized with this type of system.(author)

  6. Respiration and phosphorylation in liver and kidney mitochondria of rats exposed to high-energy gamma and beta radiation

    Energy Technology Data Exchange (ETDEWEB)

    Mokhoreva, S I; Vetlugina, N S

    1973-01-01

    The effect of whole-body irradiation with ..gamma.. rays (radiation source /sup 60/Co) at 40 rad and ..beta.. rays (source, a linear accelerator, electron energy 25 MeV) at 43 rad on oxidative phosphorylation in liver and kidney mitochondria was studied in rats. Gamma radiation gradually slowed the esterification of phosphate and respiratory rate during the oxidation of succinate in the liver and kidney mitochondria. The decrease was largest on day 15 after irradiation. However, the P/O ratio did not decrease by more than 10 to 12 percent. Despite the oxidation of glutamate in the mitochondria, respiration, phosphate consumption, and P/O ratio scarcely changed. Irradiation with electrons slowed the rate of oxidation of succinate and glutamate in liver mitochondria within 3 to 7 days. Phosphate consumption decreased at the same time so that the P/O ratio remained unchanged. Beta irradiation had virtually no effect on liver mitochondria. There is a discussion of the mechanism of action of high-energy radiation on the phosphorylation system of the mitochondria.

  7. FPDCYS and FPSPEC: computer programs for calculating fission-product beta and gamma multigroup spectra from ENDF/B-IV data

    International Nuclear Information System (INIS)

    Stamatelatos, M.G.; England, T.R.

    1977-05-01

    FPDCYS and FPSPEC are two FORTRAN computer programs used at the Los Alamos Scientific Laboratory (LASL), in conjunction with the CINDER-10 program, for calculating cumulative fission-product beta and/or gamma multigroup spectra in arbitrary energy structures, and for arbitrary neutron irradiation periods and cooling times. FPDCYS processes ENDF/B-IV fission-product decay energy data to generate multigroup beta and gamma spectra from individual ENDF/B-IV fission-product nuclides. FPSPEC further uses these spectra and the corresponding nuclide activities calculated by the CINDER-10 code to produce cumulative beta and gamma spectra in the same energy grids in which FPDCYS generates individual isotope decay spectra. The code system consisting of CINDER-10, FPDCYS, and FPSPEC has been used for comparisons with experimental spectra and continues to be used at LASL for generating spectra in special user-oriented group structures. 3 figures

  8. Interferon beta 1, an intermediate in the tumor necrosis factor alpha- induced increased MHC class I expression and an autocrine regulator of the constitutive MHC class I expression

    OpenAIRE

    1987-01-01

    In conclusion, our observations indicate that the constitutive MHC class I expression is regulated by autocrine production of IFN-beta 1. TNF-alpha acts as an enhancer of the autocrine production of IFN-beta 1, and consequently as an enhancer of the MHC class I expression and viral protection.

  9. A straightforward and efficient method for the synthesis of diversely substituted {beta}-aminoketones and {gamma}-aminoalcohols from 3-(N,N-dimethylamino)propiophenones as starting materials

    Energy Technology Data Exchange (ETDEWEB)

    Abonia, Rodrigo; Arteaga, Danny; Castillo, Juan; Insuasty, Braulio; Quiroga, Jairo; Ortiz, Alejandro, E-mail: rodrigo.abonia@correounivalle.edu.co [Universidad del Valle, Cali (Colombia). Department of Chemistry. Research Group of Heterocyclic Compounds

    2013-09-15

    Libraries of novel {beta}-aminoketones and {gamma}-aminoalcohols showing a wide structural diversity were easily obtained from a simple approach, using 3-(N,N-dimethylamino)propiophenone derivatives as key starting material. The procedure involved initially an N-alkylation of secondary benzylamines with propiophenone salts yielding the desired {beta}-aminoketones. Chemical or catalytic reduction of their carbonyl groups provided the final {gamma}-aminoalcohols in good yields. This protocol proved to be convenient as an alternative route for the synthesis of the local anesthetic Falicain Registered-Sign and for the topic antifungal drug Naftifine Registered-Sign . (author)

  10. Porphyromonas gulae Activates Unprimed and Gamma Interferon-Primed Macrophages via the Pattern Recognition Receptors Toll-Like Receptor 2 (TLR2), TLR4, and NOD2

    Science.gov (United States)

    Holden, James A.; O'Brien-Simpson, Neil M.; Lenzo, Jason C.; Orth, Rebecca K. H.; Mansell, Ashley

    2017-01-01

    ABSTRACT Porphyromonas gulae is an anaerobic, Gram-negative coccobacillus that has been associated with periodontal disease in companion animals. The aims of this study were to analyze the ligation of pattern recognition receptors by P. gulae and the subsequent activation of macrophages. Exposure of HEK cells transfected with Toll-like receptors (TLRs) or NOD-like receptors to P. gulae resulted in the ligation of TLR2, TLR4, and NOD2. The effects of this engagement of receptors were investigated by measuring the synthesis of nitric oxide (NO), CD86 expression, and inflammatory cytokine production by wild-type, TLR2−/−, and TLR4−/− macrophages. The addition of P. gulae to unprimed and gamma interferon (IFN-γ)-primed (M1 phenotype) macrophages significantly increased the surface expression of CD86, but only M1 macrophages produced nitric oxide. P. gulae-induced expression of CD86 on unprimed macrophages was dependent on both TLR2 and TLR4, but CD86 expression and NO production in M1 macrophages were only TLR2 dependent. P. gulae induced an increase in secretion of interleukin-1α (IL-1α), IL-1β, IL-6, IL-12p70, IL-13, tumor necrosis factor alpha (TNF-α), granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1α (MIP-1α) by M1 macrophages compared to that by unprimed controls. Among these cytokines, secretion of IL-6 and TNF-α by M1 macrophages was dependent on either TLR2 or TLR4. Our data indicate that TLR2 and TLR4 are important for P. gulae activation of unprimed macrophages and that activation and effector functions induced in M1 macrophages by P. gulae are mainly dependent on TLR2. In conclusion, P. gulae induces a strong TLR2-dependent inflammatory M1 macrophage response which may be important in establishing the chronic inflammation associated with periodontal disease in companion animals. PMID:28630066

  11. Use of an Interferon Gamma Release Assay (IGRA) to test T-cell responsiveness to soluble Leishmania infantum antigen in whole blood of dogs from endemic areas.

    Science.gov (United States)

    Zribi, Lilia; El-Goulli, Amel F; Ben-Abid, Meriem; Gharbi, Mohamed; Ben-Sghaier, Ines; Boufaden, Imed; Aoun, Karim; Bouratbine, Aïda

    2017-11-15

    Interferon-Gamma (IFN-γ) Release Assays (IGRAs) are easy tests that allow rapid screening of primed memory T-cells immunity in response to antigen. The aim of this study was to use IGRA to assess IFN-γ release in response to Soluble Leishmania infantum antigen (SLA) in whole blood of dogs living in endemic area of visceral leishmaniasis and to interpret IGRA results according to clinical examination, specific anti-Leishmania humoral response and presence of L. infantum DNA in blood. The study was carried out on 56 dogs living in greater Tunis area. Physical examination, quantitative serology and PCR on blood were used to characterize dogs' status in relation to Leishmania infection and disease. IGRA consisted on testing by ELISA for IFN-γ-secretion in whole blood after a 20-h challenge with SLA. PBS and Phytohemagglutinin (PHA) stimulations were used as controls. Four groups of dogs were characterized: 31 were negative by both serology and PCR, two had doubtful serology, 10 presented no to mild clinical signs but low antibodies levels and 13 were affected by Canine Leishmaniasis (CanL). In seronegative dogs, IGRA was little contributory in 4 puppies (age dogs (median age=72months, IQR: 45-84 months) that didn't respond to PHA stimulation, IGRA was negative in 19 and positive in three animals with lymph node enlargement. In dogs with doubtful serology, IGRA was positive in one dog and negative in the other. In infected dogs with no to mild clinical signs, one dog exhibited high level of IFN-γ in absence of antigenic stimulation and all the other were positive by IGRA. CanL dogs showed variable IGRA results. Negative IGRAs (n=4) were shown in animals with the highest parasitic burden whereas positive IGRAs (n=5) were shown in dogs with negative PCR or low parasitic load. The 4 remaining dogs either didn't respond to PHA (n=2) or showed non-specific secretion in PBS tube (n=2). The results of this study showed that IGRA is a useful new tool that can assess

  12. Development and evaluation of an interferon gamma assay for the diagnosis of tuberculosis in red deer experimentally infected with Mycobacterium bovis.

    Science.gov (United States)

    Risalde, María Ángeles; Thomas, Jobin; Sevilla, Iker; Serrano, Miriam; Ortíz, Jose Antonio; Garrido, Joseba; Domínguez, Mercedes; Domínguez, Lucas; Gortázar, Christian; Ruíz-Fons, Jose Francisco

    2017-11-16

    Red deer (Cervus elaphus) is regarded as an epidemiologically relevant host for Mycobacterium bovis (M. bovis) and closely related members of the Mycobacterium tuberculosis complex that cause animal tuberculosis (TB). The standard antemortem screening test for the detection of TB in deer is the intradermal tuberculin skin test, but the detection of interferon-gamma (IFNγ) produced by white blood cells exposed to M. bovis antigens can be used as an alternative or supplemental assay in most TB eradication/control programs. This study aims to develop an in-house sandwich ELISA for deer IFNγ, based on the cross-reactivity of the antibodies to both cervid and bovine IFNγ, and to evaluate the potential of this assay to detect M. bovis-infected red deer in response to the in vitro stimulation of whole-blood cells with bovine purified protein derivative (bPPD), p22 protein complex derived from bPPD or using the specific tuberculous mycobacterial proteins ESAT-6/CFP-10, Rv3615c and Rv3020c. The positive control stimulant used in this study was pokeweed mitogen, which resulted in a consistent induction of IFNγ in samples from red deer, thus allowing the interpretation of the assay. The percentage of animals correctly classified by this technique as M. bovis non-infected was 100%. The detection of infected animals as positive was high and ranged widely depending upon the antigen and the cut-off value applied, as well as the time after infection. Our findings indicate that this protocol may serve as a reliable assay for the antemortem diagnosis of TB from the initial stage of M. bovis-infection, and may also be adequately sensitive. The suggested optimal antigens and cut-off are bPPD, p22 and the combination of ESAT-6/CFP-10 and Rv3020c with a 0.05 Δ optical density, which yielded a up to 100% correct classification of TB positive and negatve red deer under our experimental conditions. This technique will aid in TB testing of farmed and translocated deer. Future studies

  13. Effects of single-dose atorvastatin on interleukin-6, interferon gamma, and myocardial no-reflow in a rabbit model of acute myocardial infarction and reperfusion

    International Nuclear Information System (INIS)

    Zhao, X.J.; Liu, X.L.; He, G.X.; Xu, H.P.

    2014-01-01

    The mechanisms of statins relieving the no-reflow phenomenon and the effects of single-dose statins on it are not well known. This study sought to investigate the effects of inflammation on the no-reflow phenomenon in a rabbit model of acute myocardial infarction and reperfusion (AMI/R) and to evaluate the effects of single-dose atorvastatin on inflammation and myocardial no-reflow. Twenty-four New Zealand white male rabbits (5-6 months old) were randomized to three groups of eight: a sham-operated group, an AMI/R group, and an atorvastatin-treated group (10 mg/kg). Animals in the latter two groups were subjected to 4 h of coronary occlusion followed by 2 h of reperfusion. Serum levels of interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. The expression of interferon gamma (IFN-γ) in normal and infarcted (reflow and no-reflow) myocardial tissue was determined by immunohistochemical methods. The area of no-reflow and necrosis was evaluated pathologically. Levels of serum IL-6 were significantly lower in the atorvastatin group than in the AMI/R group (P<0.01). Expression of IFN-γ in infarcted reflow and no-reflow myocardial tissue was also significantly lower in the atorvastatin group than in the AMI/R group. The mean area of no-reflow [47.01% of ligation area (LA)] was significantly smaller in the atorvastatin group than in the AMI/R group (85.67% of LA; P<0.01). The necrosis area was also significantly smaller in the atorvastatin group (85.94% of LA) than in the AMI/R group (96.56% of LA; P<0.01). In a secondary analysis, rabbits in the atorvastatin and AMI/R groups were divided into two groups based on necrosis area (90% of LA): a small group (<90% of LA) and a large group (>90% of LA). There was no significant difference in the area of no-reflow between the small (61.40% of LA) and large groups (69.87% of LA; P>0.05). Single-dose atorvastatin protected against inflammation and myocardial no-reflow and reduced infarct size during AMI/R in

  14. Effects of single-dose atorvastatin on interleukin-6, interferon gamma, and myocardial no-reflow in a rabbit model of acute myocardial infarction and reperfusion

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, X. J. [Affiliated Hospital of Binzhou Medical University, Department of Cardiology, Binzhou, China, Department of Cardiology, Affiliated Hospital of Binzhou Medical University, Binzhou (China); Liu, X. L. [Qilu Hospital, Shandong University, Department of Cardiology, Jinan, China, Department of Cardiology, Qilu Hospital, Shandong University, Jinan (China); He, G. X. [Third Military Medical University, Southwest Hospital, Department of Cardiology, Chongqing, China, Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing (China); Xu, H. P. [Affiliated Hospital of Binzhou Medical University, Department of Cardiology, Binzhou, China, Department of Cardiology, Affiliated Hospital of Binzhou Medical University, Binzhou (China)

    2014-03-03

    The mechanisms of statins relieving the no-reflow phenomenon and the effects of single-dose statins on it are not well known. This study sought to investigate the effects of inflammation on the no-reflow phenomenon in a rabbit model of acute myocardial infarction and reperfusion (AMI/R) and to evaluate the effects of single-dose atorvastatin on inflammation and myocardial no-reflow. Twenty-four New Zealand white male rabbits (5-6 months old) were randomized to three groups of eight: a sham-operated group, an AMI/R group, and an atorvastatin-treated group (10 mg/kg). Animals in the latter two groups were subjected to 4 h of coronary occlusion followed by 2 h of reperfusion. Serum levels of interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. The expression of interferon gamma (IFN-γ) in normal and infarcted (reflow and no-reflow) myocardial tissue was determined by immunohistochemical methods. The area of no-reflow and necrosis was evaluated pathologically. Levels of serum IL-6 were significantly lower in the atorvastatin group than in the AMI/R group (P<0.01). Expression of IFN-γ in infarcted reflow and no-reflow myocardial tissue was also significantly lower in the atorvastatin group than in the AMI/R group. The mean area of no-reflow [47.01% of ligation area (LA)] was significantly smaller in the atorvastatin group than in the AMI/R group (85.67% of LA; P<0.01). The necrosis area was also significantly smaller in the atorvastatin group (85.94% of LA) than in the AMI/R group (96.56% of LA; P<0.01). In a secondary analysis, rabbits in the atorvastatin and AMI/R groups were divided into two groups based on necrosis area (90% of LA): a small group (<90% of LA) and a large group (>90% of LA). There was no significant difference in the area of no-reflow between the small (61.40% of LA) and large groups (69.87% of LA; P>0.05). Single-dose atorvastatin protected against inflammation and myocardial no-reflow and reduced infarct size during AMI/R in

  15. Oleylphosphocholine (OlPC) arrests Cryptosporidium parvum growth in vitro and prevents lethal infection in interferon gamma receptor knock-out mice.

    Science.gov (United States)

    Sonzogni-Desautels, Karine; Renteria, Axel E; Camargo, Fabio V; Di Lenardo, Thomas Z; Mikhail, Alexandre; Arrowood, Michael J; Fortin, Anny; Ndao, Momar

    2015-01-01

    Cryptosporidium parvum is a species of protozoa that causes cryptosporidiosis, an intestinal disease affecting many mammals including humans. Typically, in healthy individuals, cryptosporidiosis is a self-limiting disease. However, C. parvum can cause a severe and persistent infection that can be life-threatening for immunocompromised individuals, such as AIDS patients. As there are no available treatments for these patients that can cure the disease, there is an urgent need to identify treatment options. We tested the anti-parasitic activity of the alkylphosphocholine oleylphosphocholine (OlPC), an analog of miltefosine, against C. parvum in in vitro and in vivo studies. In vitro experiments using C. parvum infected human ileocecal adenocarcinoma cells (HCT-8 cells) showed that OlPC has an EC50 of 18.84 nM. Moreover, no cell toxicity has been seen at concentrations ≤50 μM. C57BL/6 interferon gamma receptor knock-out mice, were infected by gavage with 4000 C. parvum oocysts on Day 0. Oral treatments, with OlPC, miltefosine, paromomycin or PBS, began on Day 3 post-infection for 10 days. Treatment with OlPC, at 40 mg/kg/day resulted in 100% survival, complete clearance of parasite in stools and a 99.9% parasite burden reduction in the intestines at Day 30. Doses of 30 and 20 mg/kg/day also demonstrated an increased survival rate and a dose-dependent parasite burden reduction. Mice treated with 10 mg/kg/day of miltefosine resulted in 50% survival at Day 30. In contrast, control mice, treated with PBS or 100 mg/kg/day of paromomycin, died or had to be euthanized between Days 6 and 13 due to severe illness. Results of parasite burden were obtained by qPCR and cross-validated by both flow cytometry of stool oocysts and histological sections of the ileum. Together, our results strongly support that OlPC represents a potential candidate for the treatment of C. parvum infections in immunocompromised patients.

  16. Porphyromonas gulae Activates Unprimed and Gamma Interferon-Primed Macrophages via the Pattern Recognition Receptors Toll-Like Receptor 2 (TLR2), TLR4, and NOD2.

    Science.gov (United States)

    Holden, James A; O'Brien-Simpson, Neil M; Lenzo, Jason C; Orth, Rebecca K H; Mansell, Ashley; Reynolds, Eric C

    2017-09-01

    Porphyromonas gulae is an anaerobic, Gram-negative coccobacillus that has been associated with periodontal disease in companion animals. The aims of this study were to analyze the ligation of pattern recognition receptors by P. gulae and the subsequent activation of macrophages. Exposure of HEK cells transfected with Toll-like receptors (TLRs) or NOD-like receptors to P. gulae resulted in the ligation of TLR2, TLR4, and NOD2. The effects of this engagement of receptors were investigated by measuring the synthesis of nitric oxide (NO), CD86 expression, and inflammatory cytokine production by wild-type, TLR2 -/- , and TLR4 -/- macrophages. The addition of P. gulae to unprimed and gamma interferon (IFN-γ)-primed (M1 phenotype) macrophages significantly increased the surface expression of CD86, but only M1 macrophages produced nitric oxide. P. gulae- induced expression of CD86 on unprimed macrophages was dependent on both TLR2 and TLR4, but CD86 expression and NO production in M1 macrophages were only TLR2 dependent. P. gulae induced an increase in secretion of interleukin-1α (IL-1α), IL-1β, IL-6, IL-12p70, IL-13, tumor necrosis factor alpha (TNF-α), granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1α (MIP-1α) by M1 macrophages compared to that by unprimed controls. Among these cytokines, secretion of IL-6 and TNF-α by M1 macrophages was dependent on either TLR2 or TLR4. Our data indicate that TLR2 and TLR4 are important for P. gulae activation of unprimed macrophages and that activation and effector functions induced in M1 macrophages by P. gulae are mainly dependent on TLR2. In conclusion, P. gulae induces a strong TLR2-dependent inflammatory M1 macrophage response which may be important in establishing the chronic inflammation associated with periodontal disease in companion animals. Copyright © 2017 American Society for Microbiology.

  17. Oleylphosphocholine (OlPC arrests Cryptosporidium parvum growth in vitro and prevents lethal infection in interferon gamma receptor knock-out mice

    Directory of Open Access Journals (Sweden)

    Karine eSonzogni-Desautels

    2015-09-01

    Full Text Available Cryptosporidium parvum is a species of protozoa that causes cryptosporidiosis, an intestinal disease affecting many mammals including humans. Typically, in healthy individuals, cryptosporidiosis is a self-limiting disease. However, C. parvum can cause a severe and persistent infection that can be life-threatening for immunocompromised individuals, such as AIDS patients. As there are no available treatments for these patients that can cure the disease, there is an urgent need to identify treatment options. We tested the anti-parasitic activity of the alkylphosphocholine oleylphosphocholine (OlPC, an analog of miltefosine, against C. parvum in in vitro and in vivo studies. In vitro experiments using C. parvum infected human ileocecal adenocarcinoma cells (HCT-8 cells showed that OlPC has an EC50 of 18.84 nM. Moreover, no cell toxicity has been seen at concentrations ≤50 µM. C57BL/6 interferon gamma receptor knock-out mice, were infected by gavage with 4000 C. parvum oocysts on Day 0. Oral treatments, with OlPC, miltefosine, paromomycin or PBS, began on Day 3 post-infection for 10 days. Treatment with OlPC, at 40 mg/kg/day resulted in 100% survival, complete clearance of parasite in stools and a 99.9% parasite burden reduction in the intestines at Day 30. Doses of 30 mg/kg/day and 20 mg/kg/day also demonstrated an increased survival rate and a dose-dependent parasite burden reduction. Mice treated with 10 mg/kg/day of miltefosine resulted in 50% survival at Day 30. In contrast, control mice, treated with PBS or 100 mg/kg/day of paromomycin, died or had to be euthanized between Days 6 and 13 due to severe illness. Results of parasite burden were obtained by qPCR and cross-validated by both flow cytometry of stool oocysts and histological sections of the ileum. Together, our results strongly support that OlPC represents a potential candidate for the treatment of C. parvum infections in immunocompromised patients.

  18. Interferon Gamma Release Assay versus Tuberculin Skin Testing among Healthcare Workers of Highly Diverse Origin in a Moderate Tuberculosis Burden Country.

    Directory of Open Access Journals (Sweden)

    Sahal Al Hajoj

    Full Text Available Health care workers (HCW's are always at an increased risk of contracting tuberculosis (TB infection. In Saudi Arabia, Interferon Gamma Release Assay (IGRA has not been evaluated as a screening tool for latent TB infection (LTBI among HCW's considering their high demographic diversity. During February 2012 to January 2015 a cross sectional study has been conducted in a tertiary care center with maximum demographically diverse staff population in the capital city-Riyadh. After a short interview and consenting, all the candidates were subjected to tuberculin skin test (TST and QuantiFERON TB gold In-tube test (QFT. A logistic regression analysis was carried out for establishing the associations between putative risk factors and the diagnostic tests. The candidates were classified according to geographical origin and a detailed analysis was conducted on the impact of their origin towards the results of TST and QFT. Of the 1595 candidates enrolled, 90.6% were BCG vaccinated, female (67.9% and mainly nurses (53.2%. Candidates with high risk of suspected or confirmed TB patient exposure were 56.1% and 76.5% of them had <10 year's work experience. TST positivity was observed in 503 (31.5% candidates, while QFT was positive among 399 (25%. Majority of the candidates were non-Saudi (83% and predominantly (52.4% from Western Pacific region. Concordant results were obtained in 14.2% of positive cases and 57.7% negative cases. The disagreements between the two tests were relatively high (kappa co-efficient-0.312±0.026, p value- <0.00001 as TST positive/QFT negative discordance was 54.8% while TST negative/QFT positive discordance was 15.7%. Age of the candidates, BCG vaccination, and South East Asian origin were associated with TST positivity while Occupational TB exposure and geographical origin of the candidates were associated with QFT positivity. A regular follow up on recently TST converted candidates showed no progression to active TB. The putative

  19. Gut Microbiota in Type 2 Diabetes Individuals and Correlation with Monocyte Chemoattractant Protein1 and Interferon Gamma from Patients Attending a Tertiary Care Centre in Chennai, India

    Directory of Open Access Journals (Sweden)

    Premalatha Pushpanathan

    2016-01-01

    Full Text Available Background: Type 2 diabetes mellitus (T2DM and obesity are associated with changes in gut microbiota and characterized by chronic low-grade inflammation. Monocyte chemoattractant protein-1 (MCP-1 and interferon gamma (IFNγ are proinflammatory cytokines which play an important role in the development of T2DM. We undertook this study to analyze the gut microbiota of T2DM and nondiabetic subjects and to determine the profile of MCP 1 and IFNγ in the same subjects attending a tertiary care center in Chennai, Tamil Nadu, India. Methods: The study included 30 subjects with clinical details. Stool and blood samples were collected from all the subjects. DNA was extracted from fecal samples and polymerase chain reaction was done using fusion primers. Metagenomic analysis was performed using ion torrent sequencing. The reads obtained were in FASTA format and reported as operational taxonomic units. Human MCP 1 and IFNγ enzyme linked immunosorbent assay (ELISA were performed for 23 serum samples. Results: The study consisted of 30 subjects; 17 were T2DM and 13 were nondiabetics. The gut microbiota among T2DM consisted predominantly of Gram negative bacteria; Escherichia and Prevotella, when compared with the nondiabetic group with predominantly Gram positive organisms suchas Faecalibacterium, Eubacterium, and Bifidobacterium. The mean MCP-1 values in the diabetic group were 232.8 pg/ml and in the nondiabetic group 170.84 pg/ml. IFNγ (mean 385.5 pg/ml was raised in glycated hemoglobin (HbA1c group of 6.5–7.5% which was statistically significant. Association of Escherichia with T2DM and association of Bifidobacteria in the nondiabetics were also statistically significant. Conclusion: Escherichia counts were elevated in T2DM with HbA1c of 6.5–8.5% which was statistically significant suggesting that lipopolysaccharides present in the cell wall of Gram-negative bacteria may be responsible for low-grade inflammation as evidenced by elevated MCP-1 and

  20. Beta and gamma decay heat measurements between 0.1s--50,000s for neutron fission of 235U, 238U and 239Pu

    International Nuclear Information System (INIS)

    Schier, W.A.; Couchell, G.P.

    1993-01-01

    A helium-jet/tape-transport system is employed in the study of beta-particle and gamma-ray energy spectra of aggregate fission products as a function of time after fission. During the initial nine months of this project we have investigated the following areas: Design, assembly and characterization of a beta-particle spectrometer; Measurement of 235 U(n th ff) beta spectra for delay times 0.2 s to 12,000 s; Assembly and characterization of a 5 x 5 Nal(Tl) gamma-ray spectrometer; Measurement of 235 U(n th ff) gamma-ray spectra for delay times 0.2s to 1 5,500s; Assembly and characterization of HPGe gamma-ray spectrometer with a Nal(Tl) Compton-and-background-suppression annulus; Measurement of 235 U(n th ,ff) high-resolution gamma-ray spectra for delay times 0.6 s to over 100,000 s; Comparison of individual gamma-line intensities with ENDF/B-VI; Adaptation to our computer of unfolding program FERDO for beta and gamma aggregate fission-product energy spectra and development of a spectrum-stripping program for analysis of HPGe gamma-ray spectra; Study of the helium-jet fission-fragment elemental transfer efficiency. This work has resulted in the publication of twelve BAPS abstracts of presentations at scientific meetings. There are currently four Ph.D. and two M.S. candidates working on dissertations associated with the project

  1. Two Modes of the Axonal Interferon Response Limit Alphaherpesvirus Neuroinvasion

    Directory of Open Access Journals (Sweden)

    Ren Song

    2016-02-01

    Full Text Available Infection by alphaherpesviruses, including herpes simplex virus (HSV and pseudorabies virus (PRV, typically begins at epithelial surfaces and continues into the peripheral nervous system (PNS. Inflammatory responses are induced at the infected peripheral site prior to invasion of the PNS. When the peripheral tissue is first infected, only the innervating axons are exposed to this inflammatory milieu, which includes the interferons (IFNs. The fundamental question is how do PNS cell bodies respond to these distant, potentially damaging events experienced by axons. Using compartmented cultures that physically separate neuron axons from cell bodies, we found that pretreating isolated axons with beta interferon (IFN-β or gamma interferon (IFN-γ significantly diminished the number of herpes simplex virus 1 (HSV-1 and PRV particles moving in axons toward the cell bodies in a receptor-dependent manner. Exposing axons to IFN-β induced STAT1 phosphorylation (p-STAT1 only in axons, while exposure of axons to IFN-γ induced p-STAT1 accumulation in distant cell body nuclei. Blocking transcription in cell bodies eliminated antiviral effects induced by IFN-γ, but not those induced by IFN-β. Proteomic analysis of IFN-β- or IFN-γ-treated axons identified several differentially regulated proteins. Therefore, unlike treatment with IFN-γ, IFN-β induces a noncanonical, local antiviral response in axons. The activation of a local IFN response in axons represents a new paradigm for cytokine control of neuroinvasion.

  2. Tuberculin-purified protein derivative-, MPT-64-, and ESAT-6-stimulated gamma interferon responses in medical students before and after Mycobacterium bovis BCG vaccination and in patients with tuberculosis

    DEFF Research Database (Denmark)

    Johnson, P D; Stuart, R L; Grayson, M L

    1999-01-01

    QuantiFERON-TB (QIFN) (CSL Limited) is a whole-blood assay for the recognition of infection with Mycobacterium tuberculosis. QIFN measures gamma interferon (IFN-gamma) production when purified protein derivatives (PPDs) of mycobacteria are incubated with venous blood samples. The specificity...... of QIFN in medical students before and after BCG immunization was assessed, and sensitivity in patients with tuberculosis was assessed. Antigens were PPD derived from M. tuberculosis and two M. tuberculosis-specific proteins, ESAT-6 and MPT-64. Of 60 medical students, all of whom had 0-mm tuberculin skin...... tests (TSTs) at study entry, 58 (97%) were initially classified as negative for M. tuberculosis infection by PPD QIFN. Five months after BCG immunization, 7 of 54 students (13%) had a TST result of >/=10 mm and 11 of 54 students (20%) tested positive by PPD QIFN. ESAT-6- and MPT-64-stimulated IFN...

  3. Clinical effectiveness and cost-effectiveness of beta-interferon and glatiramer acetate for treating multiple sclerosis: systematic review and economic evaluation.

    Science.gov (United States)

    Melendez-Torres, G J; Auguste, Peter; Armoiry, Xavier; Maheswaran, Hendramoorthy; Court, Rachel; Madan, Jason; Kan, Alan; Lin, Stephanie; Counsell, Carl; Patterson, Jacoby; Rodrigues, Jeremy; Ciccarelli, Olga; Fraser, Hannah; Clarke, Aileen

    2017-09-01

    At the time of publication of the most recent National Institute for Health and Care Excellence (NICE) guidance [technology appraisal (TA) 32] in 2002 on beta-interferon (IFN-β) and glatiramer acetate (GA) for multiple sclerosis, there was insufficient evidence of their clinical effectiveness and cost-effectiveness. To undertake (1) systematic reviews of the clinical effectiveness and cost-effectiveness of IFN-β and GA in relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) and clinically isolated syndrome (CIS) compared with best supportive care (BSC) and each other, investigating annualised relapse rate (ARR) and time to disability progression confirmed at 3 months and 6 months and (2) cost-effectiveness assessments of disease-modifying therapies (DMTs) for CIS and RRMS compared with BSC and each other. Searches were undertaken in January and February 2016 in databases including The Cochrane Library, MEDLINE and the Science Citation Index. We limited some database searches to specific start dates based on previous, relevant systematic reviews. Two reviewers screened titles and abstracts with recourse to a third when needed. The Cochrane tool and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and Philips checklists were used for appraisal. Narrative synthesis and, when possible, random-effects meta-analysis and network meta-analysis (NMA) were performed. Cost-effectiveness analysis used published literature, findings from the Department of Health's risk-sharing scheme (RSS) and expert opinion. A de novo economic model was built for CIS. The base case used updated RSS data, a NHS and Personal Social Services perspective, a 50-year time horizon, 2014/15 prices and a discount rate of 3.5%. Outcomes are reported as incremental cost-effectiveness ratios (ICERs). We undertook probabilistic sensitivity analysis. In total, 6420 publications were identified, of which 63 relating to 35 randomised

  4. Application of Monte Carlo method in study of the padronization for radionuclides with complex disintegration scheme in 4{pi}{beta}-{gamma} coincidence System; Aplicacao do metodo de Monte Carlo no estudo da padronizacao de radionuclideos com esquema de desintegracao complexos em sistema de coincidencias 4{pi}{beta}-{gamma}

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Mauro Noriaki

    2006-07-01

    The present work described a new methodology for modelling the behaviour of the activity in a 4{pi}{beta}-{gamma} coincidence system. The detection efficiency for electrons in the proportional counter and gamma radiation in the NaI(Tl) detector was calculated using the Monte Carlo program MCNP4C. Another Monte Carlo code was developed which follows the path in the disintegration scheme from the initial state of the precursor radionuclide, until the ground state of the daughter nucleus. Every step of the disintegration scheme is sorted by random numbers taking into account the probabilities of all {beta}{sup -} branches, electronic capture branches, transitions probabilities and internal conversion coefficients. Once the final state was reached beta, electronic capture events and gamma transitions are accounted for the three spectra: beta, gamma and coincidence variation in the beta efficiency was performed simulating energy cut off or use of absorbers (Collodion). The selected radionuclides for simulation were: {sup 134}Cs, {sup 72}Ga which disintegrate by {beta}{sup -} transition, {sup 133}Ba which disintegrates by electronic capture and {sup 35}S which is a beta pure emitter. For the latter, the Efficiency Tracing technique was simulated. The extrapolation curves obtained by Monte Carlo were filled by the Least Square Method with the experimental points and the results were compared to the Linear Extrapolation method. (author)

  5. Copper(II) 12-metallacrown-4 complexes of alpha-, beta- and gamma-aminohydroxamic acids: a comparative thermodynamic study in aqueous solution.

    Science.gov (United States)

    Tegoni, Matteo; Remelli, Maurizio; Bacco, Dimitri; Marchiò, Luciano; Dallavalle, Francesco

    2008-05-28

    A complete thermodynamic study of the protonation and Cu(II) complex formation equilibria of a series of alpha- and beta-aminohydroxamic acids in aqueous solution was performed. The thermodynamic parameters obtained for the protonation of glycine-, (S)-alpha-alanine-, (R,S)-valine-, (S)-leucine-, beta-alanine- and (R)-aspartic-beta-hydroxamic acids were compared with those previously reported for gamma-amino- and (S)-glutamic-gamma-hydroxamic acids. The enthalpy/entropy parameters calculated for the protonation microequilibria of these three types of ligands are in very good agreement with the literature values for simple amines and hydroxamic acids. The pentanuclear complexes [Cu5L4H(-4)]2+ contain the ligands acting as (NH2,N-)-(O,O-) bridging bis-chelating and correspond to 12-metallacrown-4 (12-MC-4) which are formed by self-assembly between pH 4 and 6 with alpha-aminohydroxamates (HL), while those with beta- and gamma-derivatives exist in a wider pH range (4-11). The stability order of these metallomacrocycles is beta- > alpha- > gamma-aminohydroxamates. The formation of 12-MC-4 with alpha-aminohydroxamates is entropy-driven, and that with beta-derivatives is enthalpy-driven, while with gamma-GABAhydroxamate both effects occur. These results are interpreted on the basis of specific enthalpies or entropy contributions related to chelate ring dimensions, charge neutralization and solvation-desolvation effects. The enthalpy/entropy parameters of 12-MC-4 with alpha-aminohydroxamic acids considered are also dependent on the optical purity of the ligands. Actually, that with (R,S)-valinehydroxamic acid presents an higher entropy and a lower enthalpy value than those of enantiopure ligands, although the corresponding stabilities are almost equivalent. Moreover, DFT calculations are in agreement with a more exothermic enthalpy found for metallacrowns with enantiomerically pure ligands.

  6. Interferon-beta treatment associated with a biochemical profile suggestive of acromegaly. A case report of a patient treated for multiple sclerosis

    DEFF Research Database (Denmark)

    Andreassen, Mikkel; Frystyk, Jan; Miller, K.K.

    2010-01-01

    We describe a 34-year-old female treated with IFN-beta for 8 years with a biochemical profile suggestive of acromegaly. The patient presented with elevated serum insulin-like growth factor-I (IGF-I) and insufficient suppression of growth hormone (GH) during oral glucose tolerance test (OGTT......). There were no clinical features of acromegaly. A 5-day profile showed higher GH levels on the 3 days following IFN-beta injections. Total and bioactive IGF-I were also elevated but did not fluctuate. Four weeks off IFN-beta normalized suppression of GH during OGTT but did not reduce serum IGF-I or bioactive...... IGF-I. In conclusion, IFN-beta treatment mimicked acromegaly biochemically. The changes were partially reversible...

  7. Desarrollo de panuveítis por tuberculosis en paciente con esclerosis múltiple tratado con interferón beta

    Directory of Open Access Journals (Sweden)

    Lucía Echevarría Lucas

    2016-09-01

    Los linfocitos CD4+ T, leucocitos, macrófagos y granulocitos, con la producción de sus mediadores interferón gamma, IL-12 o TNF-α son fundamentales para controlar al Mycobacterium tuberculosis. Por ello, antes de introducir Interferón beta 1b, convendría realizar técnicas de screening, como la prueba de Mantoux o el interferon gamma release assay–(quantiferon-TB para detectar posibles tuberculosis latentes potencialmente activables.

  8. Beta-delayed gamma and neutron emission near the double shell closure at 78Ni

    International Nuclear Information System (INIS)

    Rykaczewski, Krzysztof Piotr; Mazzocchi, C.; Grzywacz, R.; Batchelder, J. C.; Bingham, C.R.; Fong, D.; Hamilton, J.H.; Hwang, J.K.; Karny, M.; Krolas, W.; Liddick, S. N.; Morton, A. C.; Mantica, P. F.; Mueller, W. F.; Steiner, M.; Stolz, A.; Winger, J.A.

    2005-01-01

    An experiment was performed at the National Superconducting Cyclotron Laboratory at Michigan State University to investigate β decay of very neutron-rich cobalt isotopes. Beta-delayed neutron emission from 71-74 Co has been observed for the first time. Preliminary results are reported

  9. Standardization of electron-capture and complex beta-gamma radionuclides by the efficiency extrapolation method

    International Nuclear Information System (INIS)

    Grigorescu, L.

    1976-07-01

    The efficiency extrapolation method was improved by establishing ''linearity conditions'' for the discrimination on the gamma channel of the coincidence equipment. These conditions were proved to eliminate the systematic error of the method. A control procedure for the fulfilment of linearity conditions and estimation of residual systematic error was given. For law-energy gamma transitions an ''equivalent scheme principle'' was established, which allow for a correct application of the method. Solutions of Cs-134, Co-57, Ba-133 and Zn-65 were standardized with an ''effective standard deviation'' of 0.3-0.7 per cent. For Zn-65 ''special linearity conditions'' were applied. (author)

  10. Literature systematic review on the ophthalmological side effects of interferons

    Directory of Open Access Journals (Sweden)

    Yara Dadalti Fragoso

    2011-08-01

    Full Text Available Interferons alpha and beta have been used worldwide for a few decades, altering the natural history of several severe diseases including hepatitis C, cancer and immune-mediated conditions such as multiple sclerosis. The adverse events profile of interferons is well established, but only isolated reports of ophthalmological complications of interferon therapy have been published. The objective of this study was to carry out a literature systematic review on the subject, bringing to light the need for careful ophthalmological monitoring of patients undergoing interferon treatment. Nearly 500 cases of ophthalmological complications related to interferon have been reported. The most frequent findings were soft exudates, hemorrhages and retina ischemia.

  11. Contribution to the study of the sintering mechanisms of uranium powders in the {alpha}, {beta}, and {gamma} phases; Contribution a l'etude des mecanismes de frittage de poudre d'uranium en phases {alpha}, {beta}, et {gamma}

    Energy Technology Data Exchange (ETDEWEB)

    Pinteau, B [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1964-06-01

    This study of the sintering mechanisms of uranium powders prepared by calci-thermy has been effected using continuous dilatometric measurements of the shrinkage of samples previously compressed at room temperature in purified argon gas. The tests carried out in the {alpha}, {beta} and {gamma} phases have led to the observation that the first step of the sintering appears to be governed by a volume self-diffusion mechanism; the activation heat values found for the sintering mechanisms are close to those deduced during studies of volume self-diffusion using the direct radio-tracer method. Furthermore it has been possible to show that in the {gamma} domain a second sintering mechanism occurs involving much longer sintering times; the heats of activation are much lower and this appears to indicate that there occurs a mechanism involving pore elimination by grain boundary diffusion of the vacancies. Furthermore, the dilatometric tests have shown the simultaneous influence of two important parameters in this work: grain boundaries and the diffusion coefficients. In the second part of the report are given results concerning the examination of sintered samples by various methods with a view to elucidating their structure and some of their physical properties. In this way it has been possible, by carrying out metallographic examinations after etching by ionic bombardment, to determine the changes in the porosity of the three phases {alpha}, {beta} and {gamma}, as well as the structure and the nature of the inclusions in each sample. Density and porosity measurements have also been carried out. The variations in these two sets of results make it possible to confirm the preceding dilatometric end micro-graphic examinations. Finally a detailed dilatometric study of the samples sintered in the {gamma} phase has shown the effect of oxide layers, associated with the existence of porosity, on the amplitudes and temperatures of the allotropic transformations, these latter being

  12. Peripheral blood IFN-gamma-secreting V alpha 24(+)V beta 11(+) NKT cell numbers are decreased in cancer patients independent of tumor type or tumor load

    NARCIS (Netherlands)

    Molling, JW; Kolgen, W; van der Vliet, HJJ; Boomsma, MF; Kruizenga, H; Smorenburg, CH; Molenkamp, BG; Langendijk, JA; Leemans, CR; von Blomberg, BME; Scheper, RJ; van den Eertwegh, AJM

    2005-01-01

    Natural killer T (NKT) cells are CDld-restricted lvmphoid cells and are characterized by an invariant T-cell receptor, which in humans consists of a V alpha 24 chain paired with a V beta 11 chain. These cells are known for their rapid production of large amounts of cytokines (e.g., IFN-gamma and

  13. Serotonin Transporter (5-HTT) and gamma-Aminobutyric Acid Receptor Subunit beta3 (GABRB3) Gene Polymorphisms are not Associated with Autism in the IMGSA Families

    DEFF Research Database (Denmark)

    Maestrini, E.; Lai, C.; Marlow, A.

    1999-01-01

    Previous studies have suggested that the serotonin transporter (5-HTT) gene and the gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene, or other genes in the 15q11-q13 region, are possibly involved in susceptibility to autism. To test this hypothesis we performed an association study on...

  14. Development of high sensitivity gamma and beta sensors for in situ diffusion tests in the mudstone in France

    International Nuclear Information System (INIS)

    Lin, Zhenhua

    2017-01-01

    The precise monitoring of radiotracers, for example used for medical imaging, for the storage of ultimate waste, or for certain industrial applications can be a very complex subject. The development of low-noise sensors with long-term stability and high geometric flexibility were engaged by the AXINT company. (Hautefeuille, et al., 2006). My PhD thesis was focused on experiments in the diffusion of radiotracers, typically to monitor the possible leakage of radioactive products from the geological repositories. We focuses on the study of the "2"2Na and "3"6Cl ion diffusion, which is one of the highest cation and anions diffusion rate in geological medium, as well as actinides, which represent the majority of the radioactive elements of Stored nuclear waste. This thesis is in continuity with the research carried out by ANDRA (National Agency for Radioactive Waste), under contract with the laboratory ILM (Institute Light Matter), of which AXINT is the main subcontractor. The present project describes the research work that foreseen the radiation impact on the environment for the coming years during the deep disposal of nuclear waste. Our work focus on the investigation and quantification of the radionuclide diffusion through the geological clay barriers. A new in situ experiment was considered by Andra for the study of the radionuclide migration. Compared to previous experiments, this new in situ diffusion test required longer distance (hundreds of mm), longer time-scale (over 10 years), and real time in situ monitoring of radionuclides migration. To fulfill these conditions, the work was organized as following: 1: Conception and dimensional design of the Diffusion of Radio Nuclide (DRN) experiments in solving emission of beta and gamma radiations 2: Development of corresponding beta and gamma monitoring systems by means of sensors located in peripheral boreholes. (author) [fr

  15. Decay profiles of {beta} and {gamma} for a radionuclide inventory in equilibrium cycle of a BWR type reactor; Perfiles de decaimiento de radiacion {beta} y {gamma} para un inventario de radionuclidos en ciclo de equilibrio de un reactor tipo BWR

    Energy Technology Data Exchange (ETDEWEB)

    Salaices, M.; Sandoval, S.; Ovando, R. [Instituto de Investigaciones Electricas. Gerencia de Energia Nuclear, Av. Reforma 113 Col. Palmira. 62490 Cuernavaca, Morelos (Mexico)]. e-mail: sal@iie.org.mx

    2007-07-01

    Presently work the {beta} and {gamma} radiation decay profiles for a radionuclides inventory in equilibrium cycle of a BWR type reactor is presented. The profiles are presented in terms of decay in the activity of the total inventory as well as of the chemical groups that conform the inventory. In the obtaining of the radionuclides inventory in equilibrium cycle the ORIGEN2 code, version 1 was used, which simulates fuel burnup cycles and it calculates the evolution of the isotopic composition as a result of the burnt one, irradiation and decay of the nuclear fuel. It can be observed starting from the results that the decrease in the activity for the initial inventory and the different chemical groups that conform it is approximately proportional to the base 10 logarithm of the time for the first 24 hours of having concluded the burnt one. It can also be observed that the chemical groups that contribute in more proportion to the total activity of the inventory are the lanthanides-actinides and the transition metals, with 39% and 28%, respectively. The groups of alkaline earth metals, halogens, metalloids, noble gases and alkaline metals, contribute with percentages that go from the 8 to 5%. The groups that less they contribute to the total activity of the inventory they are the non metals and semi-metals with smaller proportions that 1%. The chemical groups that more contribute to the energy of {beta} and {gamma} radiation its are the transition metals and the lanthanides-actinides with a change in the order of importance at the end of the 24 hours period. The case of the halogens is of relevance for the case of the {gamma} radiation energy due that occupying the very near third site to the dimensions of the two previous groups. Additionally, the decay in the activity for the total inventory and the groups that conform it can be simulated by means of order 6 polynomials or smaller than describe its behavior appropriately. The results presented in this work, coupled

  16. Robust Protection against Highly Virulent Foot-and-Mouth Disease Virus in Swine by Combination Treatment with Recombinant Adenoviruses Expressing Porcine Alpha and Gamma Interferons and Multiple Small Interfering RNAs

    Science.gov (United States)

    Park, Jong-Hyeon; Lee, Kwang-Nyeong; Kim, Se-Kyung; You, Su-Hwa; Kim, Taeseong; Tark, Dongseob; Lee, Hyang-Sim; Seo, Min-Goo; Kim, Byounghan

    2015-01-01

    ABSTRACT Because the currently available vaccines against foot-and-mouth disease (FMD) provide no protection until 4 to 7 days postvaccination, the only alternative method to halt the spread of the FMD virus (FMDV) during outbreaks is the application of antiviral agents. Combination treatment strategies have been used to enhance the efficacy of antiviral agents, and such strategies may be advantageous in overcoming viral mechanisms of resistance to antiviral treatments. We have developed recombinant adenoviruses (Ads) for the simultaneous expression of porcine alpha and gamma interferons (Ad-porcine IFN-αγ) as well as 3 small interfering RNAs (Ad-3siRNA) targeting FMDV mRNAs encoding nonstructural proteins. The antiviral effects of Ad-porcine IFN-αγ and Ad-3siRNA expression were tested in combination in porcine cells, suckling mice, and swine. We observed enhanced antiviral effects in porcine cells and mice as well as robust protection against the highly pathogenic strain O/Andong/SKR/2010 and increased expression of cytokines in swine following combination treatment. In addition, we showed that combination treatment was effective against all serotypes of FMDV. Therefore, we suggest that the combined treatment with Ad-porcine IFN-αγ and Ad-3siRNA may offer fast-acting antiviral protection and be used with a vaccine during the period that the vaccine does not provide protection against FMD. IMPORTANCE The use of current foot-and-mouth disease (FMD) vaccines to induce rapid protection provides limited effectiveness because the protection does not become effective until a minimum of 4 days after vaccination. Therefore, during outbreaks antiviral agents remain the only available treatment to confer rapid protection and reduce the spread of foot-and-mouth disease virus (FMDV) in livestock until vaccine-induced protective immunity can become effective. Interferons (IFNs) and small interfering RNAs (siRNAs) have been reported to be effective antiviral agents against

  17. A NIM (Nuclear Instrumentation Module) system conjugated with optional input for pHEMT amplifier for beta and gamma spectroscopy

    International Nuclear Information System (INIS)

    Konrad, Barbara; Lüdke, Everton

    2014-01-01

    This work presents a high speed NIM module (Nuclear Instrumentation Module) to detect radiation, gamma and muons, as part of a system for natural radiation monitoring and of extraterrestrial origin. The subsystem developed consists of a preamplifier and an integrated SCA (Single Channel Analyzer), including power supplies of ± 12 and ± 24V with derivations of +3.6 and ± 5V. The single channel analyzer board, consisting of discrete logic components, operating in window modes, normal and integral. The pulse shaping block is made up of two voltage comparators working at 120 MHz with a response time > 60 ns and a logic anticoincidence system. The preamplifier promotes a noise reduction and introduces the impedance matching between the output of anode / diode photomultiplier tubes (PMTs) and subsequent equipment, providing an input impedance of 1MΩ and output impedance of 40 to 140Ω. The shaper amplifier is non-inverting and has variable input capacitance of 1000 pF. The upper and lower thresholds of the SCA are adjustable from 0 to ± 10V, and the equipment is compatible with various types of detectors, like PMTs coupled to sodium iodide crystals. For use with liquid scintillators and photodiodes with crystals (CsI: Tl) is proposed to include a preamplifier circuit pHEMT (pseudomorphic High Electron Mobility Transistor) integrated. Yet, the system presents the possibility of applications for various purposes of gamma spectroscopy and automatic detection of events producing of beta particles

  18. Comparative Analysis Electroencephalographic of Alpha, Beta and Gamma Bands of a Healthy Individual and One with Hemiparesis

    Science.gov (United States)

    Machado, Dionis de Castro Dutra; Lima, Glenda Crispim; Souza dos Santos, Rodrigo; Ramos, Amanda Júlia Bezerra; Menezes de Sousa, Cáio César; Moreira dos Santos, Rayele Pricila; Coelho, Karyna Kelly Oliveira; Cagy, Mauricio; Orsini, Marco; Bastos, Victor Hugo

    2014-01-01

    [Purpose] The study analyzed the electroencephalographic (EEG) data of the central cortical areas, during execution of the motor gestures of feeding, activation of the system of mirror neurons, and imagery between a right hemiparetic volunteer (RHV) and a healthy volunteer (HV). [Subjects and Methods] The volunteers’ EEG data were recorded with their eyes open for 4 minutes while they performed five experimental tasks. [Results] The alpha band, absolute power value of HV was lower than that of RHV. In the beta band, during the practice condition, there was an increase in the magnitude of the absolute power value of HV at T3, possibly because T3 is representative of secondary motor areas that work with cortical neurons related to planning and organizing sequence of movements performed by the hands. The gamma band is related to the state of preparation for movement and memory. The results of this study indicate that there was increased activation of the gamma frequency band of HV. [Conclusion] The findings of this study have revealed the changes in pattern characteristics of each band which may be associated with the brain injury of the hemiparetic patient. PMID:25013270

  19. Hydrogen bonds between the alpha and beta subunits of the F1-ATPase allow communication between the catalytic site and the interface of the beta catch loop and the gamma subunit.

    Science.gov (United States)

    Boltz, Kathryn W; Frasch, Wayne D

    2006-09-19

    F(1)-ATPase mutations in Escherichia coli that changed the strength of hydrogen bonds between the alpha and beta subunits in a location that links the catalytic site to the interface between the beta catch loop and the gamma subunit were examined. Loss of the ability to form the hydrogen bonds involving alphaS337, betaD301, and alphaD335 lowered the k(cat) of ATPase and decreased its susceptibility to Mg(2+)-ADP-AlF(n) inhibition, while mutations that maintain or strengthen these bonds increased the susceptibility to Mg(2+)-ADP-AlF(n) inhibition and lowered the k(cat) of ATPase. These data suggest that hydrogen bonds connecting alphaS337 to betaD301 and betaR323 and connecting alphaD335 to alphaS337 are important to transition state stabilization and catalytic function that may result from the proper alignment of catalytic site residues betaR182 and alphaR376 through the VISIT sequence (alpha344-348). Mutations betaD301E, betaR323K, and alphaR282Q changed the rate-limiting step of the reaction as determined by an isokinetic plot. Hydrophobic mutations of betaR323 decreased the susceptibility to Mg(2+)-ADP-AlF(n)() inhibition and lowered the number of interactions required in the rate-limiting step yet did not affect the k(cat) of ATPase, suggesting that betaR323 is important to transition state formation. The decreased rate of ATP synthase-dependent growth and decreased level of lactate-dependent quenching observed with alphaD335, betaD301, and alphaE283 mutations suggest that these residues may be important to the formation of an alternative set of hydrogen bonds at the interface of the alpha and beta subunits that permits the release of intersubunit bonds upon the binding of ATP, allowing gamma rotation in the escapement mechanism.

  20. Functional modulation of cerebral gamma-aminobutyric acidA receptor/benzodiazepine receptor/chloride ion channel complex with ethyl beta-carboline-3-carboxylate: Presence of independent binding site for ethyl beta-carboline-3-carboxylate

    Energy Technology Data Exchange (ETDEWEB)

    Taguchi, J.; Kuriyama, K. (Kyoto Prefectural Univ. of Medicine (Japan))

    1990-05-01

    Effect of ethyl beta-carboline-3-carboxylate (beta-CCE) on the function of gamma-aminobutyric acid (GABA)A receptor/benzodiazepine receptor/chloride ion channel complex was studied. Beta-CCE noncompetitively and competitively inhibited (3H)flunitrazepam binding to benzodiazepine receptor, but not (3H)muscimol binding to GABAA receptor as well as t-(3H)butylbicycloorthobenzoate (( 3H) TBOB) binding to chloride ion channel, in particulate fraction of the mouse brain. Ro15-1788 also inhibited competitively (3H) flunitrazepam binding. On the other hand, the binding of beta-(3H)CCE was inhibited noncompetitively and competitively by clonazepam and competitively by Ro15-1788. In agreement with these results, benzodiazepines-stimulated (3H)muscimol binding was antagonized by beta-CCE and Ro15-1788. Gel column chromatography for the solubilized fraction from cerebral particulate fraction by 0.2% sodium deoxycholate (DOC-Na) in the presence of 1 M KCl indicated that beta-(3H)CCE binding site was eluted in the same fraction (molecular weight, 250,000) as the binding sites for (3H)flunitrazepam, (3H)muscimol and (3H)TBOB. GABA-stimulated 36Cl- influx into membrane vesicles prepared from the bovine cerebral cortex was stimulated and attenuated by flunitrazepam and beta-CCE, respectively. These effects of flunitrazepam and beta-CCE on the GABA-stimulated 36Cl- influx were antagonized by Ro15-1788. The present results suggest that the binding site for beta-CCE, which resides on GABAA receptor/benzodiazepine receptor/chloride ion channel complex, may be different from that for benzodiazepine. Possible roles of beta-CCE binding site in the allosteric inhibitions on benzodiazepine binding site as well as on the functional coupling between chloride ion channel and GABAA receptor are also suggested.

  1. Increased antigen presentation but impaired T cells priming after upregulation of interferon-beta induced by lipopolysaccharides is mediated by upregulation of B7H1 and GITRL.

    Directory of Open Access Journals (Sweden)

    Fang Wang

    Full Text Available Dendritic cells are able to present Ag-derived peptides on MHC class I and II molecules and induce T cells priming. Lipopolysaccharides (LPS, an activator of Toll-like 4 receptor (TLR4 signaling, has been demonstrated to facilitate Ag-presentation, up-regulate surface molecules expression but impair T cells priming. In this study, we investigated the effect of LPS on nicotine-enhanced DCs-dependent T cells priming and the mechanisms of LPS orchestrating the immunosuppressive program. We could demonstrate that the treatment with LPS resulted in increased surface molecules expression, enhanced Ag-presentation, up-regulated release of TGF-beta, TNF-alpha, IL-6, and IFN-beta. Concomititantly, the upregulation of IFN-beta in DCs induces the up-regulation of coinhibitory molecules B7H1 and GITRL, which cause an impaired activation of naïve Ag-specific T cells and the induction of T cell tolerance by enhancing B7H1-PD-1 interactions and promoting GITRL-GITL facilitated Treg generation, respectively. These data provide a mechanistic basis for the immunomodulatory action of IFN-beta which might open new possibilities in the development of therapeutic approaches aimed at the control of excessive immune response and persistent infection.

  2. Persistent interferon transgene expression by RNA interference-mediated silencing of interferon receptors.

    Science.gov (United States)

    Takahashi, Yuki; Vikman, Elin; Nishikawa, Makiya; Ando, Mitsuru; Watanabe, Yoshihiko; Takakura, Yoshinobu

    2010-09-01

    The in vivo half-life of interferons (IFNs) is very short, and its extension would produce a better therapeutic outcome in IFN-based therapy. Delivery of IFN genes is one solution for providing a sustained supply. IFNs have a variety of functions, including the suppression of transgene expression, through interaction with IFN receptors (IFNRs). This suppression could prevent IFNs from being expressed from vectors delivered. Silencing the expression of IFNAR and IFNGR, the receptors for type I and II IFNs, respectively, in cells expressing IFNs may prolong transgene expression of IFNs. Mouse melanoma B16-BL6 cells or mouse liver were selected as a site expressing IFNs (not a target for IFN gene therapy) and IFN-expressing plasmid DNA was delivered with or without small interfering RNA (siRNA) targeting IFNRs. Transfection of B16-BL6 cells with siRNA targeting IFNAR1 subunit (IFNAR1) resulted in the reduced expression of I