WorldWideScience

Sample records for beta interferon gamma

  1. Alpha/Beta and Gamma Interferons Are Induced by Infection with Noncytopathic Bovine Viral Diarrhea Virus In Vivo

    OpenAIRE

    Charleston, B; Brackenbury, L.S; Carr, B. V.; Fray, M D; Hope, Jayne; Howard, CJ; Morrison, Ivan

    2002-01-01

    In contrast to the results of previous in vitro studies, experimental infection of calves with noncytopathic bovine viral diarrhea virus (ncpBVDV) was found to induce strong alpha/beta and gamma interferon responses in gnotobiotic animals. These responses were associated with depressed levels of transforming growth factor beta (TGF-beta) in serum. The results of this study indicate that the immunosuppression caused by ncpBVDV is not associated with low interferon responses or elevated levels ...

  2. Interferon Beta-1b Injection

    Science.gov (United States)

    Interferon beta-1b injection is used to reduce episodes of symptoms in patients with relapsing-remitting (course ... and problems with vision, speech, and bladder control). Interferon beta-1b is in a class of medications ...

  3. 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 severe, malignant osteopetrosis (an inherited bone disease). Interferon gamma-1b is in a class of medications ...

  4. Interferon-gamma is a strong modulator of NK susceptibility and expression of beta 2-microglobulin but not of transferrin receptors of K562 cells.

    Science.gov (United States)

    Grönberg, A; Kiessling, R; Fiers, W

    1985-10-01

    The human cell line K562 was treated with human natural leukocyte interferon (IFN-alpha) and recombinant immune interferon (IFN-gamma). Cell cultures exposed to both types of IFNs displayed a reduced susceptibility to the cytotoxic activity of human PBL (NK activity). While this effect occurred preferentially at high doses of IFN-alpha, as little as 10 U/ml of IFN-gamma caused a marked decrease in susceptibility to NK-cell-mediated lysis. Using a monoclonal antibody against human beta2-microglobulin (beta2M) a low level of specific binding to K562 cells was detected. The binding increased after treatment with IFN-alpha (1.4-fold) and IFN-gamma (1.7-fold). The expression of transferrin receptors (TR) was not changed significantly. A hybrid cell line between K562 and a Burkitt's lymphoma-derived cell line displayed a similar pattern of response to IFN-alpha and IFN-gamma as did K562, when effects on NK susceptibility, beta2M expression, and TR expression were studied. The Burkitt's lymphoma line PUT showed no consistent changes in expression of beta2M and TR. These results demonstrate that IFN-gamma is highly efficient in modulating the NK susceptibility, and the expression of beta2M on K562. The presented data do not support a role for expression of TR as the only property that determines the degree of NK susceptibility, since there was no correlation between NK susceptibility and TR expression among the cell lines tested or when IFN-treated and untreated cells were compared.

  5. The antiviral response to gamma interferon.

    Science.gov (United States)

    Costa-Pereira, Ana P; Williams, Timothy M; Strobl, Birgit; Watling, Diane; Briscoe, James; Kerr, Ian M

    2002-09-01

    A role for alpha/beta interferon (IFN-alpha/beta) in the IFN-gamma antiviral response has long been suggested. Accordingly, possible roles for autocrine or double-stranded-RNA (dsRNA)-induced IFN-alpha/beta in the IFN-gamma response were investigated. Use was made of wild-type and a variety of mutant human fibrosarcoma cell lines, including mutant U5A cells, which lack a functional IFN-alpha/beta receptor and hence an IFN-alpha/beta response. IFN-gamma did not induce detectable levels of IFN-alpha/beta in any of the cell lines, nor was the IFN-gamma response per se dependent on autocrine IFN-alpha/beta. On the other hand, a number of responses to dsRNA [poly(I). poly(C)] and encephalomyocarditis virus were greatly enhanced by IFN-gamma pretreatment (priming) of wild-type cells or of mutant cells lacking an IFN-alpha/beta response; these include the primary induction of dsRNA-inducible mRNAs, including IFN-beta mRNA, and, to a lesser extent, the dsRNA-mediated activation of the p38 mitogen-activated protein (MAP) kinase(s). IFN-gamma priming of mRNA induction by dsRNA is dependent on JAK1 and shows biphasic kinetics, with an initial rapid (<30-min) response being followed by a more substantial effect on overnight incubation. The IFN-gamma-primed dsRNA responses appear to be subject to modulation through the p38, phosphatidylinositol 3-kinase, and ERK1/ERK2 MAP kinase pathways. It can be concluded that despite efficient priming of IFN-beta production, the IFN-alpha/beta pathways play no significant role in the primary IFN-gamma antiviral response in these cell-virus systems. The observed IFN-gamma priming of dsRNA responses, on the other hand, will likely play a significant role in combating virus infection in vivo.

  6. Recombinant mouse interferon-gamma regulation of antibody production.

    OpenAIRE

    Johnson, H M; Torres, B A

    1983-01-01

    Interferon-gamma produced in monkey cells by transfection with mouse interferon-gamma cDNA suppressed the mouse in vitro antibody response in a manner similar to that of natural mouse interferon-gamma. Significant suppression was obtained with as little as 1 U of interferon. Recombinant human interferon-gamma produced by cloning in a similar fashion was not suppressive. Both the suppressive and the antiviral activities of recombinant interferon-gamma were neutralized by antibodies to mouse na...

  7. 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...

  8. 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. MET

  9. Cerebral malaria: gamma-interferon redux

    Directory of Open Access Journals (Sweden)

    Nicholas H Hunt

    2014-08-01

    Full Text Available There are two theories that seek to explain the pathogenesis of cerebral malaria, the mechanical obstruction hypothesis and the immunopathology hypothesis. Evidence consistent with both ideas has accumulated from studies of the human disease and experimental models. Thus some combination of these concepts seems necessary to explain the very complex pattern of changes seen in cerebral malaria. The interactions between malaria parasites, erythrocytes, the cerebral microvascular endothelium, brain parenchymal cells, platelets and microparticles need to be considered. One factor that seems able to knit together much of this complexity is the cytokine interferon-gamma. In this review we consider findings from the clinical disease, in vitro models and the murine counterpart of human cerebral malaria in order to evaluate the roles played by interferon-gamma in the pathogenesis of this often fatal and debilitating condition.

  10. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-06-01

    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.

  12. Inhibition of growth of Toxoplasma gondii in cultured fibroblasts by human recombinant gamma interferon.

    Science.gov (United States)

    Pfefferkorn, E R; Guyre, P M

    1984-01-01

    The growth of Toxoplasma gondii in cultured human fibroblasts was inhibited by recombinant human gamma interferon at concentrations of 8 to 16 U/ml. The interferon was titrated by observing a total inhibition of parasite plaque formation 7 days after infection. Inhibition of the growth of T. gondii in the early days after infection was measured by marked reductions in the incorporation of radioactive uracil, a precursor that can only be used by the parasites. This assay showed that when cells were pretreated with gamma interferon for 1 day and then infected, inhibition of T. gondii growth could be readily detected 1 or 2 days after infection. When the pretreatment was omitted and parasites and gamma interferon were added at the same time, no inhibition of parasite growth could be detected 1 day later, although it was apparent after 2 days. Cultures from which the gamma interferon had been removed by washing after a 1-day treatment showed inhibition of T. gondii growth. Gamma interferon had no effect on the viability of extracellular parasites, but it did inhibit the synthesis of host cell RNA and protein by ca. 50% 3 days after treatment. This degree of inhibition is unlikely, of itself, to compromise the growth of T. gondii. Recombinant alpha and beta interferons had no effect on the growth of T. gondii. Images PMID:6425215

  13. Beta-gamma discriminator circuit

    International Nuclear Information System (INIS)

    The major difficulty encountered in the determination of beta-ray dose in field conditions is generally the presence of a relatively high gamma-ray component. Conventional dosimetry instruments use a shield on the detector to estimate the gamma-ray component in comparison with the beta-ray component. More accurate dosimetry information can be obtained from the measured beta spectrum itself. At Los Alamos, a detector and discriminator circuit suitable for use in a portable spectrometer have been developed. This instrument will discriminate between gammas and betas in a mixed field. The portable package includes a 256-channel MCA which can be programmed to give a variety of outputs, including a spectral display, and may be programmed to read dose directly

  14. Mechanism of inhibition of HSV-1 replication by tumor necrosis factor and interferon gamma.

    Science.gov (United States)

    Feduchi, E; Carrasco, L

    1991-02-01

    Tumor necrosis factor (TNF) synergizes with interferon (IFN gamma) in the blockade of HSV-1 replication. Antibodies against IFN beta block this synergism, implying a role of IFN beta in the antiviral activity of TNF plus IFN gamma. IFN beta 1 added exogenously to Hep-2 cells shows antiviral activity against HSV-1 only at high concentrations, whereas IFN beta 2 (also known as IL-6) alone has no effect on the replication of VSV or HSV-1 even when 1,000 U/ml are present. Our results are in accordance with the idea that TNF induces IFN beta 1 and that both cytokines must be present in the culture medium to synergize with IFN gamma in order to inhibit HSV-1 replication.

  15. 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.

  16. Shared receptor components but distinct complexes for alpha and beta interferons.

    Science.gov (United States)

    Lewerenz, M; Mogensen, K E; Uzé, G

    1998-09-25

    The type I interferon family includes 13 alpha, one omega and one beta subtypes recognized by a complex containing the receptor subunits ifnar1 and ifnar2 and their associated Janus tyrosine kinases, Tyk2 and Jak1. To investigate the reported differences in the way that alpha and beta interferons signal through the receptor, we introduced alanine-substitutions in the ifnar2 extracellular domain, and expressed the mutants in U5A cells, lacking endogenous ifnar2. A selection, designed to recover mutants that responded preferentially to alpha or beta interferon yielded three groups: I, neutral; II, sensitive to alpha interferon, partially resistant to beta interferon; III, resistant to alpha interferon, partially sensitive to beta interferon. A mutant clone, TMK, fully resistant to alpha interferon with good sensitivity to beta interferon, was characterized in detail and compared with U5A cells complemented with wild-type ifnar2 and also with Tyk2-deficient 11.1 cells, which exhibit a similar alpha-unresponsive phenotype with a partial beta interferon response. Using anti-receptor antibodies and mutant forms of beta interferon, three distinct modes of ligand interaction could be discerned: (i) alpha interferon with ifnar1 and ifnar2; (ii) beta interferon with ifnar1 and ifnar2; (iii) beta interferon with ifnar2 alone. We conclude that alpha and beta interferons signal differently through their receptors because the two ligand subtypes interact with the receptor subunits ifnar 1 and ifnar2 in entirely different ways.

  17. Interferon gamma blocks the growth of Toxoplasma gondii in human fibroblasts by inducing the host cells to degrade tryptophan.

    Science.gov (United States)

    Pfefferkorn, E R

    1984-01-01

    Treatment of human fibroblasts with human recombinant gamma interferon blocked the growth of Toxoplasma gondii, an obligate intracellular protozoan parasite. Growth of the parasite was measured by a plaque assay 7 days after infection or by the incorporation of [3H]uracil 1 or 2 days after infection. The antitoxoplasma activity induced in the host cells by gamma interferon was strongly dependent upon the tryptophan concentration of the medium. Progressively higher minimal inhibitory concentrations of gamma interferon were observed as the tryptophan concentration in the culture medium was increased. Treatment with gamma interferon did not make the cells impermeable to tryptophan. The kinetics of [3H]tryptophan uptake into the acid-soluble pools of control and gamma interferon-treated cultures were identical during the first 48 sec. Thereafter uptake of [3H]tryptophan into the acid-soluble pool of control fibroblasts reached the expected plateau after 96 sec. In contrast, uptake of [3H]tryptophan continued for at least 12 min in the gamma interferon-treated cultures. At that time, the acid-soluble pool of the gamma interferon-treated cultures contained 8 times the radioactivity of the control cultures. This continued accumulation was the result of rapid intracellular degradation of [3H]tryptophan into kynurenine and N-formylkynurenine that leaked slowly from the cells. These two metabolites were also recovered from the medium of cultures treated for 1 or 2 days with gamma interferon. Human recombinant alpha and beta interferons, which have no antitoxoplasma activity, did not induce any detectable degradation of tryptophan. Several hypotheses are presented to explain how the intracellular degradation of tryptophan induced by gamma interferon could restrict the growth of an obligate intracellular parasite. Images PMID:6422465

  18. 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....... Other biomarkers such as interferon-gamma-induced-protein 10 (IP-10) may have potential for the diagnosis of latent TB infections. OBJECTIVES: To describe IP-10 concentrations and their association to TST and INF-gamma responses in children recently exposed to adults with smear-positive TB in Brazil...

  19. Beta-glucan-depleted, glycopeptide-rich extracts from Brewer's and Baker's yeast (Saccharomyces cerevisiae) lower interferon-gamma production by stimulated human blood cells in vitro.

    Science.gov (United States)

    Williams, Roderick; Dias, Daniel A; Jayasinghe, Nirupama; Roessner, Ute; Bennett, Louise E

    2016-04-15

    Regulation of the human immune system requires controlled pro- and anti-inflammatory responses for host defence against infection and disease states. Yeasts (Saccharomyces cerevisiae), as used in brewing and baking, are mostly known for ability to stimulate the human immune-system predominantly reflecting the pro-inflammatory cell wall β-glucans. However, in this study, using food-compatible processing methods, glycopeptide-enriched and β-glucan-depleted products were each prepared from Brewer's and Baker's yeasts, which suppressed production of interferon-γ (IFN-γ) in human whole blood cell assay, signifying that anti-inflammatory factors are also present in yeast. Anti-inflammatory bioactivities of products prepared from Brewer's and Baker's yeast were compared with the commercial yeast product, Epicor®. While unfractionated Epicor was inactive, the C18 resin-binding fractions of Brewer's and Baker's yeast products and Epicor dose-dependently lowered IFN-γ, demonstrating that Epicor also contained both pro-inflammatory (β-glucans) and anti-inflammatory components. Anti-inflammatory activity was attributed to C18 resin-binding species glyco-peptides in Epicor and experimental yeast products. This study demonstrated that pro- and anti-inflammatory factors could be resolved and enriched in yeasts by suitable processing, with potential to improve specific activities.

  20. A modified immune tolerant mouse model to study the immunogenicity of recombinant human interferon beta

    NARCIS (Netherlands)

    Abdolvahab, Mohadeseh Haji; Brinks, Vera; Schellekens, Huub

    2014-01-01

    Interferon beta may induce antibodies in multiple sclerosis patients and the incidence of immunogenicity depends on the type of product. These antibodies can reduce the efficacy of interferon beta. Two transgenic immune tolerant mouse models for human interferon beta (hIFNβ) (C57Bl/6, and C57Bl/6×FV

  1. Antibodies against interferon-beta in neuromyelitis optica patients

    DEFF Research Database (Denmark)

    Asgari, Nasrin; Kyvik, Kirsten Ohm; Steenstrup, Troels;

    2014-01-01

    Neuromyelitis optica (NMO) is an antibody-mediated autoimmune inflammatory disease of the CNS. A poor response to treatment with recombinant interferon beta (IFN-ß) in NMO patients has been suggested, although the precise mechanisms remain uncertain. We analyzed occurrence and clinical consequences...

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

    DEFF Research Database (Denmark)

    Krakauer, Martin

    2007-01-01

    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...

  3. 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.

  4. Treatment with anti-interferon-gamma monoclonal antibodies modifies experimental autoimmune encephalomyelitis in interferon-gamma receptor knockout mice

    DEFF Research Database (Denmark)

    Espejo, C; Penkowa, M; Sáez-Torres, I;

    2001-01-01

    The role of interferon-gamma (IFN-gamma) in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) is still controversial. We have studied the function of IFN-gamma and its receptor in the EAE model using two different IFN-gamma receptor knockout (IFN-gamma R......(-/-)) mouse types: C57Bl/6x129Sv, with a disruption of the IFN-gamma receptor cytoplasmic domain, and 129Sv, homozygous for a disrupted IFN-gamma receptor gene. Mice were immunized with peptide 40-55 from rat myelin oligodendrocyte glycoprotein. A subgroup of mice was treated with anti-IFN-gamma monoclonal...... antibodies (mAb) on day 8 postimmunization. Clinical scoring and both histological and immunohistochemical studies were undertaken for all groups. We hereby show that treatment with anti-IFN-gamma mAb worsened the disease course of 129Sv wild-type mice. However, it decreased the mean daily score in IFN...

  5. Expression of Human Beta Defensing-2 and Interferon-gamma in Lesions of Condyloma Acuminatum%β防御素-2和γ干扰素在尖锐湿疣皮损中表达的研究

    Institute of Scientific and Technical Information of China (English)

    屈丽; 甄莉

    2013-01-01

    Objective:To study the expressions of human beta defensing-2(HBD-2)and interferon-gamma(IFN-γ)in the lesions of condyloma acuminatum,and to speculate the pathogenesis and prognosis of condyloma acuminatum.Method:Tissue specimens were collected from the lesions of 25 patients with condyloma acuminatum and 20 patients with psoriasis,as well as from the normal skin of 25 healthy controls.The specimen subjected to an immunohistochemical analysis for the detection of HBD-2 and IFN-γ.Statistical analysis was performed by using the SPSS 16.0 software package,and Wilcoxon rank sum test was carried out to compare the expressions of HBD-2 and IFN-γbetween these groups,and make correlation analysis.Result:HBD-2 and IFN-γwere observed mainly in the stratum basale of the epidermis in condyloma acuminatum.The expression levels of HBD-2 and IFN-γwere significantly lower in condyloma acuminatum than psoriasis(Z=-7.174,-7.230;P0.01).Conclusion:We speculate that HBD-2,IFN-γmay participate in condyloma acuminatum immune response process and plays a certain role.%  目的:研究和探讨β防御素-2(HBD-2)和γ干扰素(IFN-γ)在尖锐湿疣发病和预后中的作用.方法:用免疫组化法检测HBD-2和IFN-γ在25例尖锐湿疣(CA)(初发患者)皮损、20例寻常性银屑病皮损以及25例健康人皮肤石蜡切片中的表达.SPSS 16.0统计软件进行数据分析,组间行Wilcoxon秩和检验,并进行相关性分析.结果:HBD-2、IFN-γ在尖锐湿疣皮损的表达主要见于基底层, HBD-2、IFN-γ水平明显低于银屑病阳性对照组(Z=-7.174,-7.230;P0.01).结论:推测HBD-2、IFN-γ可能通过不同的途径共同参与了尖锐湿疣的免疫反应过程并发挥了一定的作用.

  6. Interferon Gamma as a Biomarker of Exposure to Enteric Viruses

    Science.gov (United States)

    Interferon gamma (IFN-γ) was selected as a biomarker for viral exposure. Twelve-week-old BALB/c mice were intraperitoneally injected with Coxsackievirus B3 or B4 diluted in phosphate-buffered saline (PBS). Control mice were injected with PBS only. Four months after viral infectio...

  7. Interferons beta have vasoconstrictive and procoagulant effects: a woman who developed livedo reticularis and Raynaud phenomenon in association with interferon beta treatment for multiple sclerosis.

    Science.gov (United States)

    Rot, Uroš; Ledinek, Alenka Horvat

    2013-12-01

    A 31-year-old woman with MS developed livedo reticularis and secondary Raynaud phenomenon 2.5 years after introduction of interferon beta-1b. The symptoms disappeared after withdrawal of the drug. Livedo reticularis and Raynaud phenomenon as well as pulmonary arterial hypertension, venous sinus thrombosis, pulmonary embolism and renal thrombotic microangiopathy have all been described in association with interferon beta therapy. These complications strongly suggest that type I interferons have vasoconstrictive and procoagulant effects with potentially serious systemic complications.

  8. Simultaneous beta/gamma digital spectroscopy

    Science.gov (United States)

    Farsoni, Abdollah T.

    A state-of-the-art radiation detection system for simultaneous spectroscopy of beta-particles and gamma-rays has been developed. The system utilizes a triple-layer phoswich detector and a customized Digital Pulse Processor (DPP) built in our laboratory. The DPP board was designed to digitally capture the analog signal pulses and, following several digital preprocessing steps, transfer valid pulses to the host computer for further digital processing. A MATLAB algorithm was developed to digitally discriminate beta and gamma events and reconstruct separate beta and gamma-ray energy spectra with minimum crosstalk. The spectrometer proved to be an effective tool for recording separate beta and gamma-ray spectra from mixed radiation fields. The system as a beta-gamma spectrometer will have broad-ranging applications in nuclear non-proliferation, radioactive waste management, worker safety, systems reliability, dose assessment, and risk analysis.

  9. Development of a Second Generation Bovigam Interferon Gamma (IFN-gamma) Assay

    Science.gov (United States)

    In search for better tools to control bovine tuberculosis, the development of diagnostic tests with improved performance and enhanced ease-of-use has a high priority. BOVIGAM®, a rapid laboratory assay, measures gamma interferon (IFN-gamma) production in whole blood samples after induction of a ce...

  10. STAT5 activation by human GH protects insulin-producing cells against interleukin-1beta, interferon-gamma and tumour necrosis factor-alpha-induced apoptosis independent of nitric oxide production

    DEFF Research Database (Denmark)

    Jensen, Janne; Galsgaard, Elisabeth D; Karlsen, Allan E;

    2005-01-01

    possible targets for the STAT5-mediated protection of INS-1E cells, we studied the effect of hGH on activation of the transcription factors STAT1 and nuclear factor-kappaB (NF-kappaB) by IFN-gamma and IL-1beta+TNF-alpha respectively. Gel retardation experiments showed that hGH affects neither IFN......-gamma+TNF-alpha-induced STAT1 DNA binding nor IL-1beta and IFN-gamma+TNF-alpha-induced NFkappaB DNA binding. The lack of influence of hGH on cytokine-mediated activation of STAT1 and NFkappaB is in accordance with the finding that hGH had only a minor effect on cytokine-induced inducible nitric oxide synthase (iNOS) gene...... and in the presence of cytotoxic cytokines. In conclusion, these results suggested that GH and PRL protect beta-cells against cytotoxic cytokines via STAT5-dependent mechanisms distal to iNOS activation possibly at the level of Bcl-xL....

  11. 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

    -beta) both in sections of spinal cords and the antigen-induced expression of these cytokines by lymphoid cells after stimulation with a dominant encephalitogenic peptide of MBP (MBP 63-88) during the course of actively induced experimental autoimmune encephalomyelitis (EAE) in Lewis rats. In spinal cords...... 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....... Such cells may act in the initiation and promotion of the disease. Later, in the recovery phase, MBP 63-88 induced lymphoid cells to TGF-beta production. Thus, an autoantigen-specific production of TGF-beta occurred during EAE and hypothetically such a mechanism may serve to downregulate aggressive...

  12. Spreading depression transiently disrupts myelin via interferon-gamma signaling.

    Science.gov (United States)

    Pusic, Aya D; Mitchell, Heidi M; Kunkler, Phillip E; Klauer, Neal; Kraig, Richard P

    2015-02-01

    Multiple sclerosis and migraine with aura are clinically correlated and both show imaging changes suggestive of myelin disruption. Furthermore, cortical myelin loss in the cuprizone animal model of multiple sclerosis enhances susceptibility to spreading depression, the likely underlying cause of migraine with aura. Since multiple sclerosis pathology involves inflammatory T cell lymphocyte production of interferon-gamma and a resulting increase in oxidative stress, we tested the hypothesis that spreading depression disrupts myelin through similar signaling pathways. Rat hippocampal slice cultures were initially used to explore myelin loss in spreading depression, since they contain T cells, and allow for controlled tissue microenvironment. These experiments were then translated to the in vivo condition in neocortex. Spreading depression in slice cultures induced significant loss of myelin integrity and myelin basic protein one day later, with gradual recovery by seven days. Myelin basic protein loss was abrogated by T cell depletion, neutralization of interferon-gamma, and pharmacological inhibition of neutral sphingomyelinase-2. Conversely, one day after exposure to interferon-gamma, significant reductions in spreading depression threshold, increases in oxidative stress, and reduced levels of glutathione, an endogenous neutral sphingomyelinase-2 inhibitor, emerged. Similarly, spreading depression triggered significant T cell accumulation, sphingomyelinase activation, increased oxidative stress, and reduction of gray and white matter myelin in vivo. Myelin disruption is involved in spreading depression, thereby providing pathophysiological links between multiple sclerosis and migraine with aura. Myelin disruption may promote spreading depression by enhancing aberrant excitability. Thus, preservation of myelin integrity may provide novel therapeutic targets for migraine with aura.

  13. DMPD: The interferon signaling network and transcription factor C/EBP-beta. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18163952 The interferon signaling network and transcription factor C/EBP-beta. Li H... The interferon signaling network and transcription factor C/EBP-beta. PubmedID 18163952 Title The interfero...n signaling network and transcription factor C/EBP-beta. Authors Li H, Gade P, Xi

  14. Influence of recombinant bovine gamma interferon on neutrophil function

    International Nuclear Information System (INIS)

    To determine the role of cytokines in enhancing neutrophil function, peripheral blood neutrophils from healthy cattle were preincubated with recombinant bovine gamma interferon (rboIFN-gamma). Pretreatment of neutrophils with rboIFN-gamma activated neutrophils to have enhanced antibody-dependent (ADCC) and -independent (AINC) cytotoxicity and impaired random migration. Neutrophil ingestion, superoxide anion production, and iodination activity were not consistently affected by rboIFN-gamma pretreatment. In order to better understand the activation process, the molecular events involved in the enhancement of neutrophil cytotoxicity and the inhibition random migration were investigated. Both RNA and protein syntheses by neutrophils were required for the enhancement of AINC activity and the inhibition of random migration, but were not required for the enhancement of ADCC by rboIFN-gamma. Specifically, rbo-IFN-gamma treatment of neutrophils enhanced the expression of two major proteins of molecular mass 60,000 and 94,000 as determined by SDS-polyacrylamide, linear-gradient gel electrophoresis and 35S-fluorography

  15. Computer simulations of human interferon gamma mutated forms

    Science.gov (United States)

    Lilkova, E.; Litov, L.; Petkov, P.; Petkov, P.; Markov, S.; Ilieva, N.

    2010-01-01

    In the general framework of the computer-aided drug design, the method of molecular-dynamics simulations is applied for investigation of the human interferon-gamma (hIFN-γ) binding to its two known ligands (its extracellular receptor and the heparin-derived oligosaccharides). A study of 100 mutated hIFN-γ forms is presented, the mutations encompassing residues 86-88. The structural changes are investigated by comparing the lengths of the α-helices, in which these residues are included, in the native hIFN-γ molecule and in the mutated forms. The most intriguing cases are examined in detail.

  16. Murine gamma interferon fails to inhibit Toxoplasma gondii growth in murine fibroblasts.

    Science.gov (United States)

    Schwartzman, J D; Gonias, S L; Pfefferkorn, E R

    1990-01-01

    Although treatment of human macrophages or fibroblasts with human gamma interferon results in the inhibition of intracellular Toxoplasma gondii, murine gamma interferon stimulated only murine macrophages, not murine fibroblasts, to inhibit T. gondii. This species difference may be important in understanding the control of acute and chronic toxoplasmosis. PMID:2106497

  17. 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...

  18. Characterization of the oligodeoxynucleotide-mediated inhibition of interferon-gamma-induced major histocompatibility complex class I and intercellular adhesion molecule-1.

    Science.gov (United States)

    Ramanathan, M; Lantz, M; MacGregor, R D; Garovoy, M R; Hunt, C A

    1994-10-01

    The major histocompatibility complex (MHC) Class I and II genes and intercellular adhesion molecule-1 (ICAM-1) are regulated by interferon-gamma in a variety of cell types. We have previously shown that the oligodeoxynucleotide 5'-GGG GTT GGT TGT GTT GGG TGT TGT GT-RNH2 (oligo I) inhibits the interferon-gamma-mediated enhancement of MHC Class I and ICAM-1 proteins in the K562 cell line. We have now investigated the mechanism of action of oligo I and report that it acts by inhibiting the binding of interferon-gamma to cells. We also show that the dose-response curves, the selectivity profile, and the kinetics of oligo I are consistent with this novel mechanism of action. The dose-response curves for oligo I, obtained using antibodies against the MHC Class I heavy chain, beta 2-microglobulin, or ICAM-1, are almost superimposable at each observation time. MHC Class I induction by 6400 units/ml interferon-alpha or interferon-beta or ICAM-1 enhancement by 800 units/ml tumor necrosis factor-alpha is not inhibited by oligo I. However, the synergistic induction of MHC Class I by mixtures of tumor necrosis factor-alpha and interferon-gamma is inhibited. Oligo I belongs to a class of active oligodeoxynucleotides that inhibits interferon-gamma-induced MHC Class I and ICAM-1 in K562 cells. The activity and potency is sequence-dependent, but remarkably different sequences can have comparable effects. The activity of oligo I in the HeLa S3 cell line inhibits the interferon-gamma-mediated enhancement of both ICAM-1 and MHC Class II DR and the interferon-gamma-mediated reduction in transferrin receptor expression. Thus, oligo I appears to specifically inhibit interferon-gamma-induced changes in protein expression, which is consistent with oligo I acting at an early step(s) in the induction process. Taken together, our results show that oligo I exerts its effects by inhibiting the association of interferon-gamma with the cell surface, which is a novel mechanism of action for

  19. Beta/gamma test problems for ITS

    International Nuclear Information System (INIS)

    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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    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...

  1. Effects of bovine viral diarrhea viruses in vitro on transcription of interferon-al- pha, beta, gamma mRNA in bovine peripheral blood mononuclear cells%牛病毒性腹泻病毒感染牛外周血单核细胞对IFN-α、β、γmRNA转录的影响

    Institute of Scientific and Technical Information of China (English)

    韩猛立; 黄新; 钟发刚

    2012-01-01

    The study was done to survery the interferon-alpha, beta and gamma mRNA transcription profiles of bovine viral diarrfea viruse(BVDV) infection,and to investigate the host-BVDV interaction. The clinically healthy Holstein cows tested negative for bovine viral diarrhea virus(BVDV) in peripheral blood mononuclear cells(PBMC) were in- fected with noncytopathic(NCP) and cytopathic(NCP) BVDV. The mRNA levels of IFN-α,β and γ genes were ana lyzed using a reaPtime fluorescent quantitative PCR(reaPtime FQ-PCR). The results indicated that the transcription of I type(IFN-α,β) mRNA showed a different increasing levels (P〈0.01) ,after infected CP- and NCP BVDV in PBMC;only IFN-α decreased at 4,12 h(P〈0. 05) after infected CP-BVDV. And IFN-γ was increased throughout the infection process of CP and NCP BVDV in PBMC (P〈0. 05). The transcription levels of IFN mRNA were in- creased when two biotype of BVDV infected in PBMC.%为了解牛病毒性腹泻病毒(BVDV)感染对干扰素(IFN)mRNA转录时相的影响,探讨宿主-病毒之间的相互关系,用非致细胞病变(noncytopathic,NCP)和致细胞病变(cytopathic,CP)型BVDV感染临床健康BVDV检测阴性的荷斯坦奶牛外周血单核细胞(PBMC),利用实时荧光定量PCR技术对感染后IFN-α、β、γmRNA转录水平的变化进行定量分析。结果表明,CP型和NCP型BVDV感染PBMC后,Ⅰ型IFN(IFN-α、β)均呈现出不同程度的转录水平上调,且差异极显著(P〈0.01);只有IFN-α在CP型BVDV感染后4,12h(P〈0.5)出现转录下调。IFN-γ在整个感染过程中均呈现出不同程度的转录水平上调,且差异显著(P〈0.05)。这表明2种生物型BVDV感染可引起PBMC中IFN mRNA转录水平升高。

  2. 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 antibo

  3. 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.......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....

  4. Enhanced expression of beta2-microglobulin and HLA antigens on human lymphoid cells by interferon

    DEFF Research Database (Denmark)

    Heron, I; Hokland, M; Berg, K

    1979-01-01

    Mononuclear cells from the blood of healthy normal humans were kept in cultures under nonstimulating conditions for 16 hr in the presence or absence of human interferon. The relative quantities of HLA antigens and beta(2)-microglobulin on the cultured cells were determined by quantitative...... was observed on B- and T-enriched lymphocyte populations and was found to be dose dependent with the optimum with "physiological" concentrations of interferon. Pretreatment of lymphocytes with interferon for 2 hr was found to be as effective as having interferon present during the total culture period...

  5. 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

    . Other biomarkers such as interferon-gamma-induced-protein 10 (IP-10) may have potential for the diagnosis of latent TB infections. OBJECTIVES: To describe IP-10 concentrations and their association to TST and INF-gamma responses in children recently exposed to adults with smear-positive TB in Brazil...... and Nepal. METHODS:: Two surveys using the same design were undertaken to describe TST, INF-gamma, and IP-10 responses in 146 children in Nepal and 113 children in Brazil. RESULTS: The concordance of TST and QuantiFERON-TB gold in-tube (QFT-IT) was high (kappa 0.73 in Brazil and 0.80 in Nepal). IP-10...... responses were higher in children with both positive TST and positive QFT-IT (medians 1434 pg/mL in Brazil and 1402 pg/mL in Nepal) and lowest in children with both negative TST and negative QFT-IT (medians 206 pg/mL in Brazil and 81 pg/mL in Nepal). Children with negative TST and positive QFT-IT had higher...

  6. Natural interferon-beta treatment for patients with chronichepatitis C in Japan

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Chronic hepatitis C virus (HCV) infection can cause liver cirrhosis and hepatocellular carcinoma (HCC).Several studies have demonstrated that the eradicationof HCV reduces the occurrence of HCC. In Japan, asmany people live to an advanced age, HCV-infectedpatients are also getting older, and the age at HCCdiagnosis has also increased. Although older HCV-infectedpatients have a risk of developing HCC, the treatmentresponse to peginterferon-alpha plus ribavirin therapy isrelatively poor in these patients because of drop-out ordiscontinuation of this treatment due to adverse events.It is established that the mechanism of action betweeninterferon-alpha and interferon-beta is slightly different.Short-term natural interferon-beta monotherapy iseffective for patients with acute hepatitis C and patientsinfected with HCV genotype 2 and low viral loads.Natural interferon-beta plus ribavirin for 48 wk or for24 wk are also effective for some patients with HCVgenotype 1 or HCV genotype 2. Natural interferon-betaplus ribavirin has been used for certain "difficult-totreat"HCV-infected patients. In the era of direct-actinganti-virals, natural interferon-beta plus ribavirin maybe one of the therapeutic options for special groupsof HCV-infected patients. In the near future, signaltransduction pathways of interferon-beta will informfurther directions.

  7. Pseudomonas aeruginosa alkaline protease degrades human gamma interferon and inhibits its bioactivity.

    OpenAIRE

    Horvat, R T; Parmely, M J

    1988-01-01

    This study was performed to determine the effect of Pseudomonas aeruginosa on gamma interferon (IFN-gamma) production by antigen-stimulated human T-cell clones. Crude bacterial filtrates prepared from certain strains of P. aeruginosa inhibited IFN-gamma production by T cells and reduced the antiviral activity of preformed IFN-gamma. Bacterial filtrates prepared from mutant strains that did not produce the exoenzyme alkaline protease (AP) did not inhibit IFN-gamma activity. The inhibitory acti...

  8. Electrochemical impedance spectroscopy based-on interferon-gamma detection

    Science.gov (United States)

    Li, Guan-Wei; Kuo, Yi-Ching; Tsai, Pei-I.; Lee, Chih-Kung

    2014-03-01

    Tuberculosis (TB) is an ancient disease constituted a long-term menace to public health. According to World Health Organization (WHO), mycobacterium tuberculosis (MTB) infected nearly a third of people of the world. There is about one new TB occurrence every second. Interferon-gamma (IFN-γ) is associated with susceptibility to TB, and interferongamma release assays (IGRA) is considered to be the best alternative of tuberculin skin test (TST) for diagnosis of latent tuberculosis infection (LTBI). Although significant progress has been made with regard to the design of enzyme immunoassays for IFN-γ, adopting this assay is still labor-intensive and time-consuming. To alleviate these drawbacks, we used IFN-γ antibody to facilitate the detection of IFN-γ. An experimental verification on the performance of IGRA was done in this research. We developed two biosensor configurations, both of which possess high sensitivity, specificity, and rapid IFN-γ diagnoses. The first is the electrochemical method. The second is a circular polarization interferometry configuration, which incorporates two light beams with p-polarization and s-polarization states individually along a common path, a four photo-detector quadrature configuration to arrive at a phase modulated ellipsometer. With these two methods, interaction between IFN-γ antibody and IFN-γ were explored and presented in detail.

  9. 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...

  10. 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

    Bacterial superantigens such as staphylococcal enterotoxin-A (SEA) have been implicated in the pathogenesis of psoriasis vulgaris. Major histocompatibility complex (MHC) class II molecules are high affinity receptors for SEA, and T cells found in psoriatic skin lesions express high levels of MHC...... are involved in the autopresentation of SEA by psoriatic T cells. In conclusion, we provide evidence that SEA directly activates MVHC class H-positive psoriatic T-cell lines to produce IFN-gamma, a key cytokine in the pathogenesis of psoriasis vulgaris....... of interferon-gamma (IFN-gamma), but not autocrine mitogenesis in CD8-positive T clones obtained from skin lesions of a patient with psoriasis vulgaris. Psoriatic T cells do not respond to SEA molecules if mutations are introduced in the TCRbeta- or in both the two MHC class II alpha- and beta-binding sites...

  11. Current Perspectives on Interferon Beta-1b for the Treatment of Multiple Sclerosis

    OpenAIRE

    Marziniak, Martin; Meuth, Sven

    2014-01-01

    Interferon (IFN) beta-1b was the first disease-modifying therapy to be approved for the treatment of multiple sclerosis (MS), and over 21 years of follow-up data demonstrate its efficacy and long-term safety profile. Following recent regulatory approvals in the USA and European Union, IFN beta-1b is now one of the seven disease-modifying therapies [intramuscular IFN beta-1a; subcutaneous (SC) IFN beta-1a; IFN beta-1b SC; glatiramer acetate SC; oral dimethyl fumarate; oral teriflunomide; and i...

  12. 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

  13. 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...

  14. 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 cytokine

  15. Immunopathologic effects associated with Sarcocystis neurona-infected interferon-gamma knockout mice

    OpenAIRE

    Witonsky, S. G.; Gogal, R. M.; Duncan, R. B.; Lindsay, D S

    2003-01-01

    Interferon-gamma knockout (IFN-gamma KO) mice were infected with Sarcocystis neurona merozoites to characterize the immunopathology associated with infection. By day 14 postinfection (PI), mice developed splenomegaly and lymphadenopathy, characterized by marked lymphoid hyperplasia with increased numbers of germinal centers. Additional histopathologic changes included increased extramedullary hematopoiesis, multifocal mixed inflammatory infiltrates in the liver, perivascular infiltrate of the...

  16. Topical Non-Invasive Gene Delivery using Gemini Nanoparticles in Interferon-gamma-deficient Mice

    Energy Technology Data Exchange (ETDEWEB)

    Badea,I.; Wettig, S.; Verrall, R.; Foldvari, M.

    2007-01-01

    Cutaneous gene therapy, although a promising approach for many dermatologic diseases, has not progressed to the stage of clinical trials, mainly due to the lack of an effective gene delivery system. The main objective of this study was to construct and evaluate gemini nanoparticles as a topical formulation for the interferon gamma (IFN-{gamma}) gene in an IFN-{gamma}-deficient mouse model. Nanoparticles based on the gemini surfactant 16-3-16 (NP16-DNA) and another cationic lipid cholesteryl 3{beta}-(-N-[dimethylamino-ethyl] carbamate) [Dc-chol] (NPDc-DNA) were prepared and characterized. Zetasizer measurement indicated a bimodal distribution of 146 and 468 nm average particle sizes for the NP16-DNA ({zeta}-potential +51 mV) nanoparticles and monomodal distribution of 625 nm ({zeta}-potential +44 mV) for the NPDc-DNA. Circular dichroism studies showed that the gemini surfactant compacted the plasmid more efficiently compared to the Dc-chol. Small-angle X-ray scattering measurements revealed structural polymorphism in the NP16-DNA nanoparticles, with lamellar and Fd3m cubic phases present, while for the NPDc-DNA two lamellar phases could be distinguished. In vivo, both topically applied nanoparticles induced higher gene expression compared to untreated control and naked DNA (means of 0.480 and 0.398 ng/cm{sup 2} vs 0.067 and 0.167 ng/cm{sup 2}). However, treatment with NPDc-DNA caused skin irritation, and skin damage, whereas NP16-DNA showed no skin toxicity. In this study, we demonstrated that topical cutaneous gene delivery using gemini surfactant-based nanoparticles in IFN-{gamma}-deficient mice was safe and may provide increased gene expression in the skin due to structural complexity of NP16 nanoparticles (lamellar-cubic phases).

  17. Interleukin 1 receptor antagonist mediates the beneficial effects of systemic interferon beta in mice: implications for rheumatoid arthritis

    NARCIS (Netherlands)

    M. Corr; D.L. Boyle; L.M. Ronacher; B.R. Lew; L.G. van Baarsen; P.P. Tak; G.S. Firestein

    2011-01-01

    Objectives Interferon beta (IFN beta) therapy is effective in multiple sclerosis and murine models of arthritis. Surprisingly, systemic IFN beta treatment induces only minimal improvement in rheumatoid arthritis (RA). To explain this paradox, the authors evaluated the mechanism of IFN beta benefit i

  18. Roles of gamma interferon and interleukin-4 in genetically determined resistance to Coccidioides immitis.

    OpenAIRE

    Magee, D M; Cox, R A

    1995-01-01

    The profiles of gamma interferon (IFN-gamma) and interleukin-4 (IL-4) production were evaluated during the course of coccidioidomycosis in two inbred mouse strains which differ in their susceptibility to Coccidioides immitis. Cytokine responses, measured at the molecular and protein levels, showed increased levels of IFN-gamma in lung extracts from mice of the resistant DBA/2 strain after a pulmonary challenge, whereas the susceptible BALB/c strain manifested a predominant IL-4 response. The ...

  19. DMPD: The interferon-alpha/beta system in antiviral responses: a multimodal machineryof gene regulation by the IRF family of transcription factors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 11790540 The interferon-alpha/beta system in antiviral responses: a multimodal mach...l. 2002 Feb;14(1):111-6. (.png) (.svg) (.html) (.csml) Show The interferon-alpha/beta system in antiviral responses: a multi...ion factors. PubmedID 11790540 Title The interferon-alpha/beta system in antiviral responses: a multimodal m

  20. 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.

  1. Reduced Amount of Japanese Encephalitis Viral RNA in the Infected Cells Treated with Human Interferon Beta

    OpenAIRE

    Daji, Hu; TANAKA Mariko; Morita, Kouichi; Igarashi, Akira

    1992-01-01

    Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed that the amount of Japanese encephalitis (JE) virus-specific positive sense RNA was found to be reduced in the infected Hep-2 cells treated with human interferon beta at 1,000 IU/ml in the medium compared with untreated specimens.

  2. Natalizumab plus interferon beta-1a reduces lesion formation in relapsing multiple sclerosis

    DEFF Research Database (Denmark)

    Radue, Ernst-Wilhelm; Stuart, William H; Calabresi, Peter A;

    2010-01-01

    The SENTINEL study showed that the addition of natalizumab improved outcomes for patients with relapsing multiple sclerosis (MS) who had experienced disease activity while receiving interferon beta-1a (IFNbeta-1a) alone. Previously unreported secondary and tertiary magnetic resonance imaging (MRI...

  3. 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 c...

  4. Randomised, controlled study of intratumoral recombinant gamma-interferon treatment in newly diagnosed glioblastoma.

    OpenAIRE

    Färkkilä, M; Jääskeläinen, J.; Kallio, M. (Miki); Blomstedt, G.; Raininko, R; Virkkunen, P.; Paetau, A.; Sarelin, H.; Mäntylä, M

    1994-01-01

    The effect of intratumoral recombinant interferon gamma (rIFN-gamma) as adjuvant to open cytoreduction and external irradiation of 60 Gy on survival in adults with a newly diagnosed high-grade cerebral glioma was studied. The patients were randomised during surgery into the rIFN-gamma group (n = 14) or the control group (n = 17), and the latter received a subcutaneous reservoir of rIFN-gamma injections. Intratumoral rIFN-gamma was given three times a week for 4 weeks until radiotherapy, escal...

  5. Novel Beta-Gamma Coincidence Measurements Using Phoswich Detectors

    International Nuclear Information System (INIS)

    The PNNL has developed an Automated Radio-xenon Sampler/Analyzer (ARSA) for the CTBT to measure four radio-xenon isotopes using a beta-gamma coincidence counting detector. A novel method to measure beta-gamma coincidences using a phoswich detector with state-of-the-art pulse shape discrimination techniques has been investigated

  6. Microstructures of duplex (beta + gamma) silver-tin alloys.

    Science.gov (United States)

    Abbott, J R; Miller, D R; Netherway, D J

    1985-05-01

    The microstructures of (beta + gamma) silver-tin alloys are especially influenced by both homogenization temperature and subsequent heat treatment. When the alloy is cooled from homogenization temperatures above approximately 200 degrees C, lenticular regions of the ordered orthorhombic gamma phase precipitate from within the disordered h.c.p. beta phase on three structurally equivalent planes, (1210), (1120), and (2110), to form a Widmanstatten structure. When the duplex alloys were homogenized at temperatures below approximately 200 degrees C, where the beta/(beta + gamma) phase boundary is vertical, these structures were not observed. PMID:3858310

  7. A system for simultaneous beta and gamma spectroscopy

    Science.gov (United States)

    Farsoni, A. T.; Hamby, D. M.

    2007-08-01

    A state-of-the-art radiation detection system for real-time and simultaneous spectroscopy of beta-particles and gamma-rays has been developed. The system utilizes a triple-layer phoswich detector and a customized Digital Pulse Processor (DPP) designed and built in our laboratory. The DPP board digitally captures the analog signal pulses and, following several digital preprocessing steps, transfers valid pulses to the host computer for further digital processing. A resolving algorithm also was developed to digitally discriminate beta and gamma events, and reconstruct separate beta and gamma-ray energy spectra with minimal crosstalk. The spectrometer has proven to be an effective tool for recording separate beta and gamma-ray spectra from mixed radiation fields. The system as a beta-gamma spectrometer will have broad-ranging applications in nuclear non-proliferation, radioactive waste management, worker safety, systems reliability, dose assessment, and risk analysis.

  8. Expressions of GSK-3beta, Beta-Catenin and PPAR-Gamma in Medulloblastoma

    Institute of Scientific and Technical Information of China (English)

    Xiong Zhang; Lu Si; Yu Li; Can Mi

    2009-01-01

    Objective: To investigate the expressions of GSK-3beta, Beta-catenin and PPAR-gamma, and their relationship in medulloblastoma, and to explore their value in clinic application.Methods: Immunohistochemical staining with SP method was conducted to determine the expressions of GSK-3beta, Beta-catenin and PPAR-gamma in 48 cases of medulloblastoma and 10 normal cerebellar tissues.Results: The rate of abnormal expressions of beta-catenin and PPAR-gamma in MB was higher than that in normal. Conversely, GSK-3beta in MB was lower than that in the normal (P<0.05). Furthermore, in medulloblastoma, beta-catenin and GSK-3beta showed a negative correlation, PPAR-gamma and beta-catenin had a positive correlation.Conclusion: Abnormal expression of beta-catenin plays a crucial role in the development of medulloblastoma. Meanwhile, PPAR-gamma and GSK-3beta which are tightly related with beta-catenin are both involved in the genesis and development of medulloblastoma.

  9. Cytokines and adhesion molecules in multiple sclerosis patients treated with interferon-beta1b

    DEFF Research Database (Denmark)

    Jensen, Jakob; Krakauer, Martin; Sellebjerg, Finn

    2005-01-01

    Multiple sclerosis (MS), an inflammatory, demyelinating disease of the central nervous system (CNS), is thought to be caused by a T cell-mediated attack on CNS myelin and axons. Recombinant interferon (IFN)-beta is an established treatment of multiple sclerosis, and is known to reduce the number...... of disease relapses and the development of irreversible symptoms and signs of disease. The mechanism of action of IFN-beta treatment is, however, not completely understood. Previous studies have suggested major effects on mononuclear cell cytokine production and T cell migration, but results have been...... initiated on de novo treatment with IFN-beta1b. We found only minor associations between the different changes induced by IFN-beta1b-treatment. Our findings are consistent with changes in T cell expression of CD49d/VLA-4 and induction of sVCAM-1 as important effects of treatment with IFN-beta1b in multiple...

  10. 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 IF

  11. Effects of chicken interferon Gamma on Newcastle disease virus vaccine immunogenicity

    Science.gov (United States)

    More effective vaccines are needed to control avian diseases. The use of chicken interferon gamma (chIFN') during vaccination is a potentially important but controversial approach that may improve the immune response to antigens. In the present study, three different systems to co-deliver chIFN' wit...

  12. Capillary Electrophoretic Immunoassay with Laser-induced Fluorescence Detection for Interferon-gamma

    Institute of Scientific and Technical Information of China (English)

    Hua ZHANG; Hai Ming WEI; Wen Rui JIN

    2004-01-01

    Capillary electrophoretic immunoassay with laser-induced fluorescence detection for recombinant human interferon-gamma (IFN-γ) was established. The limits of detection for three forms of IFN-γare 6.9 ng/L, 5.7 ng/L and 5.0 ng/L, respectively.

  13. High-level production of recombinant chicken interferon-gamma by Brevibacillus choshinensis.

    Science.gov (United States)

    Yashiro, K; Lowenthal, J W; O'Neil, T E; Ebisu, S; Takagi, H; Moore, R J

    2001-10-01

    Cytokines, such as interferon-gamma have been shown to have adjuvant and growth promoting activity in poultry and livestock and have the potential to be used as alternatives to antibiotics. We have developed an efficient system for commercial-scale synthesis of recombinant chicken interferon-gamma (ChIFN-gamma) using Brevibacillus choshinensis as the host for protein production. The ChIFN-gamma expression vector, pNCIFN, was constructed using the novel Escherichia coli-B. choshinensis shuttle vector, pNCMO2. ChIFN-gamma expression was optimized by investigating different culture conditions and different host B. choshinensis mutants. The highest level of production was observed using the B. choshinensis HPD31-MB2 strain grown at 30 degrees C, where ChIFN-gamma was produced at approximately 300-500 mg/L. ChIFN-gamma was also produced as a His-tagged fusion protein by using the pNCHis-IFN expression vector, a derivative of pNCMO2. The protein was constitutively secreted into the culture supernatant and could be partially purified in a single step using a Ni-nitrilotriacetic acid column. This recombinant His-ChIFN-gamma was shown to have the same biological activity as native ChIFN-gamma. PMID:11570852

  14. 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.

  15. 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

    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...

  16. Cyclic oxidation behavior of beta+gamma overlay coatings on gamma and gamma+gamma-prime alloys

    Science.gov (United States)

    Nesbitt, J. A.; Pilsner, B. H.; Carol, L. A.; Heckel, R. W.

    1984-01-01

    Detailed experimental studies of the cyclic oxidation behavior of low-pressure plasma sprayed beta+gamma coasting on gamma-phase Ni-Cr-Al alloys have shown the correlation of weight change, oxide type, and Cr and Al concentration-distance profiles as a function of oxidation time. Of special interest was the transition to breakway oxidation due to the loss of the Al flux to the oxide and the failure of the coated alloy to form an Al2O3-rich oxide scale. The experimental results on beta+gamma/gamma coating systems were used as the basis of a numerical model (ternary, semi-infinite, finite-difference analysis) which accurately predicted changes in Cr and Al concentration-distance profiles. The model was used to study parameters critical to enhancing the life of coatings which fail by a combination of Al loss in forming the oxide scale and Al loss via interdiffusion with the substrate alloy. Comparisons of beta+gamma/gamma coating behavior are made to the oxidation of coated gamma+gamma-prime substrates, both ternary Ni-Cr-Al alloys and Mar-M 247-type alloys.

  17. In Vivo-Simulated Sonotransfection and the Effect of Gamma Interferon Gene on Neurofibroma Proliferation

    Science.gov (United States)

    Yamaguchi, Kazuki; Feril, Loreto B.; Yoshida, Yuichi; Nakayama, Juichiro; Tachibana, Katsuro

    2007-05-01

    We have previously shown that ultrasound-mediated gene transfection (or sonotransfection) can be optimized on the basis of concepts drawn from previous in vitro experiments demonstrating ultrasound-induced apoptosis. At optimized conditions, we have shown using five cancer cell lines (HeLa, U937, Meth A, T24 and PC3) that sonotransfection is superior to other conventional non-viral methods such as electroporation and liposome-mediated transfection. In the present study, we further investigate the gene transfection of pEGFP-N1 into neurofibroma cell line isolated from human dermal neurofibroma, using an improved experimental set up that simulates in vivo conditions. The ultrasound device used was SonoPore KTAC-4000, which is capable of various settings. Using transducers of centre frequency 1.011 MHz, the optimal conditions include ISATA of 0.15, 0.44 and 0.64 W/cm2, burst frequency of 0.5 Hz, 25% duty factor, and 10-40 sec exposure duration. Cells were assayed at 24, 48 and 72 hr after the sonication. The transfection efficiency was found to be around 10%. Then we further investigated whether sonotransfection of gamma interferon on neurofibroma cell lines in vivo can suppress cell proliferation. Gamma interferon is well known as a pluripotential cytokine. It exerts an anti-tumor activity in some malignant diseases such as malignant lymphoma. Gamma interferon gene transfection by use of lipofectamin has been found to markedly inhibit the proliferation of neurofibroma cell lines in vitro. Our new experimental system was applied in evaluating the effect of sonotransfected gamma interferon gene on neurofibroma proliferation in vitro. It is suggested that ultrasound-mediated gamma interferon gene transfection could potentially become a non-surgical method in treating skin diseases, such as neurofibromas, particularly in patients with von Recklinghausen's disease.

  18. Effect of interferon-gamma treatment on the course of a burn wound infection.

    Science.gov (United States)

    Hershman, M J; Sonnenfeld, G; Logan, W A; Pietsch, J D; Wellhausen, S R; Polk, H C

    1988-06-01

    Interferon-gamma (IFN-gamma) has been shown to have immunoregulatory properties and is able to modulate resistance to several microbial infections. This study was designed to determine the efficacy of IFN-gamma treatment in a murine burn wound infection model. Bacterial challenge consisted of Klebsiella pneumoniae (10(8) organisms/ml) or Pseudomonas aeruginosa (10(8) organisms/ml), applied topically immediately after burning. Groups of CBA/J mice received either IFN-gamma or RPMI-1640 medium (controls) subcutaneously. IFN-gamma was administered daily at a dose of 7,500 units for 5 days prior to bacterial challenge. Burn without bacterial challenge produced no mortality. Mice treated with IFN-gamma survived significantly longer than controls when the bacterial challenge was K. pneumoniae. There was no difference in survival when bacterial challenge was P. aeruginosa. The Ia antigen expression of peripheral blood mononuclear cells was severely reduced for 3 days post-burn. This drop was prevented on day 3 post-burn in mice treated with IFN-gamma. These data indicate that interferon was effective treatment in a murine model of Klebsiella burn wound infection and was associated with maintenance of Ia antigen expression that may have contributed to the action of the IFN-gamma. PMID:3137276

  19. Characterization of beta-R1, a gene that is selectively induced by interferon beta (IFN-beta) compared with IFN-alpha.

    Science.gov (United States)

    Rani, M R; Foster, G R; Leung, S; Leaman, D; Stark, G R; Ransohoff, R M

    1996-09-13

    We report preliminary characterization of a gene designated beta-R1, which is selectively expressed in response to interferon beta (IFN-beta) compared with IFN-alpha. In human astrocytoma cells, beta-R1 was induced to an equivalent extent by 10 IU/mL IFN-beta or 2500 IU/mL IFN-alpha2. To address the mechanism of this differential response, we analyzed induction of the beta-R1 gene in fibrosarcoma cells and derivative mutant cells lacking components required for signaling by type I IFNs. beta-R1 was readily induced by IFN-beta in the parental 2fTGH cell line, but not by recombinant IFN-alpha2, IFN-alpha Con1, or a mixture of IFN-alpha subtypes. IFN-alpha8 induced beta-R1 weakly. beta-R1 was not induced by IFN-beta in mutant cell lines U2A, U3A, U4A, and U6A, which lack, respectively, p48, STAT1, JAK1, and STAT2. U5A cells, which lack the Ifnar 2.2 component of the IFN-alpha and -beta receptor, also failed to express beta-R1. U1A cells are partially responsive to IFN-beta and IFN-alpha8 but lacked beta-R1 expression, indicating that TYK2 protein is essential for induction of this gene. Taken together, these results suggest that the expression of beta-R1 in response to type I IFN requires IFN-stimulated gene factor 3 plus an additional component, which is more efficiently formed on induction by IFN-beta compared with IFN-alpha.

  20. Menstrual Irregularities and Related Plasma Hormone Levels in Multiple Sclerosis Patients Treated with Beta Interferone

    Directory of Open Access Journals (Sweden)

    Ehya Garshasbi

    2010-02-01

    Full Text Available Multiple sclerosis is a chronic inflammatory disease of central nervous system.Women are more susceptible to this disease. One of the obvious clinical complaints in women with multiple sclerosis specially treated with Beta Interferones is menstrual cycle irregularity. The aim of this study was to determine the prevalence of menstrual irregularities and probable changes in blood levels of related hormones (FSH, LH, PRL, TSH, T4, T3 in 58 females with definite MS treated with beta interferones versus 58 healthy women. In comparison to the control group, the patients had higher prevalence of irregular menstruation (P=0.001, oligomenorrhea (p=0.03, abnormal amount of menstrual blood flow (P=0.001, abnormal duration of menstrual flow (P=0.01 and missed period (P=0.04. Mean LH level in patients group was higher than control group (P=0.04.Hyperprolactinemia (>25.5ng/ml was more prevalent in patients group .There were not a significant difference in plasma levels of FSH and thyroid hormones between two groups. There were some relations between the type of Beta interferones and the subtype of menstrual irregularities in the patients. In conclusion, the results of this study emphasized the high rate of menstrual problem and changes of related plasma hormone levels in MS patients.

  1. [Response to treatment with interferon beta in patients with multiple sclerosis. Validation of the Rio Score].

    Science.gov (United States)

    Rio, J; Rovira, A; Blanco, Y; Sainz, A; Perkal, H; Robles, R; Ramio-Torrenta, Ll; Diaz, R M; Arroyo, R; Urbaneja, P; Fernandez, O; Garcia-Merino, J A; Reyes, M P; Oreja-Guevara, C; Prieto, J M; Izquierdo, G; Olascoaga, J; Alvarez-Cermeno, J C; Simon, E; Pujal, B; Comabella, M; Montalban, X

    2016-08-16

    Introduccion. Se han propuesto diferentes criterios de respuesta al tratamiento con interferon beta, y el Rio Score es uno de los mas utilizados. El objetivo de este estudio fue validar la utilidad del Rio Score en una cohorte independiente. Pacientes y metodos. Estudio multicentrico, prospectivo y longitudinal de pacientes con esclerosis multiple remitente recurrente tratados con interferon beta. Los pacientes fueron clasificados basandose en la presencia de brotes, lesiones activas (nuevas en T2 o lesiones que captaban gadolinio) en la resonancia magnetica, incremento confirmado de la discapacidad o combinaciones de estas variables (brotes, incremento en la Expanded Disability Status Scale y lesiones activas) tras un año de tratamiento. Se utilizo un analisis de regresion con el fin de identificar las variables de prediccion de respuesta despues de un seguimiento de tres años. Resultados. Se incluyo a 249 pacientes con esclerosis multiple remitente recurrente. El modelo logistico confirmo que la presencia de dos (odds ratio = 6,6; IC 95% = 2,7-16,1; p discapacidad durante el tratamiento con interferon beta.

  2. Interferon beta-1a-induced depression and suicidal ideation in multiple sclerosis Depressão e idéias suicidas induzidas por interferon beta-1a na esclerose múltipla

    Directory of Open Access Journals (Sweden)

    Marco Aurélio Lana-Peixoto

    2002-09-01

    Full Text Available Depression and suicide have been reported in association with multiple sclerosis (MS. Some studies show that interferon beta may increase the depression rate. We report a case of depression and suicidal ideation in coincidence with the start of increased doses of interferon beta-1a and their complete reversal following the drug withdrawal. The patient was a 21-year-old man with MS and no past history of affective disorders who was given interferon beta-1a in the dose of 11 mug three times per week. As a new relapse occurred the dose of interferon beta-1a was increased to 22 mug three times a week. The patient then observed increased worry, irritability and a sense of discouragement as well as recurring suicidal thoughts. His mood was rapidly restored following interferon beta-1a withdrawal. This case suggests that patients with MS may develop depression and suicidal thoughts when treated with high doses of interferon beta-1a.Depressão e idéias suicidas são relatados na esclerose múltipla (EM. Alguns estudos demonstram que interferon beta pode aumentar sua freqüência. Relatamos o caso de um jovem de 21 anos com EM, sem história pregressa de distúrbios psiquiátricos, que vinha usando interferon beta-1a na dose de 11 mig três vezes por semana, com boa tolerância. A dose foi aumentada para 22 mig três vezes por semana após um novo surto. O paciente observou o aparecimento de fenômenos depressivos e idéias suicidas coincidindo com o aumento da dose. A suspensão da droga foi acompanhada de desaparecimento completo desses sintomas. Seis meses após a retirada do interferon beta-1a, o paciente se encontra em uso de acetato de glatiramer, não tendo mais apresentado qualquer fenômeno depressivo ou pensamentos suicidas. Este caso sugere que pacientes com EM podem desenvolver depressão e pensamentos suicidas quando tratados com doses elevadas de interferon beta-1a.

  3. delta beta-Thalassaemia in Sicily: report of a case of double heterozygosity for A gamma delta beta-thalassaemia and A gamma G gamma delta beta-thalassaemia.

    OpenAIRE

    Musumeci,S; Romeo, M A; Pizzarelli, G.; Schilirò, G; Russo, G.

    1983-01-01

    A case of double heterozygosity for A gamma delta beta-thalassaemia and A gamma G gamma delta beta-thalassaemia was found during a screening programme in Sicily. The proband, a 4-year-old girl, showed a clinical picture of thalassaemia intermedia. Hb F (85.12% by the Singer method) was G gamma A gamma type. The parents and the brother were delta beta-thalassaemia carriers. Structural analysis of Hb F showed both G gamma and A gamma chains in the father, but only A gamma chains in the mother.

  4. Fênomeno de Raynaud grave associado a terapia com interferon-beta para esclerose múltipla: relato de caso Severe Raynaud's phenomenon associated with interferon-beta therapy for multiple sclerosis: case report

    OpenAIRE

    BORIS AFONSO CRUZ; EUSTÁQUIO DE QUEIROZ; SIMONE VILELA NUNESi; ACHILES CRUZ FILHO; GILBERTO BELISARIO CAMPOS; ERNESTO LENTZ DE CARVALHO MONTEIRO; HUMBERTO CRIVELLARI

    2000-01-01

    Interferon-B (IFN-beta) é usado no tratamento de esclerose múltipla (EM). Descrevemos o caso de uma mulher com EM que apresentou fenômeno de Raynaud grave, livedo reticular e necrose digital duas semanas após tratamento com IFN-beta. Os sintomas melhoraram após suspensão do IFN-beta e início de anticoagulação associada a ciclofosfamida e corticóide. Fenômeno de Raynaud é um efeito colateral provável da terapia com IFN-beta para EM.Interferon-beta (IFN-beta) is administered for treatment of mu...

  5. Interferon-gamma confers resistance to experimental allergic encephalomyelitis

    DEFF Research Database (Denmark)

    Krakowski, M; Owens, T

    1996-01-01

    strains of mice are resistant to EAE. We have studied the effect of deletion of IFN-gamma on the ability to induce EAE in resistant BALB/c-backcrossed mice. As expected, only 0-6% of BALB/c or BALB/c-backcrossed mice developed EAE when immunized with myelin basic protein in adjuvant. Strikingly...

  6. Autocrine secretion of interferon gamma negatively regulates homing of immature B cells.

    Science.gov (United States)

    Flaishon, L; Hershkoviz, R; Lantner, F; Lider, O; Alon, R; Levo, Y; Flavell, R A; Shachar, I

    2000-11-01

    The mechanism by which immature B cells are sequestered from encountering foreign antigens present in lymph nodes or sites of inflammation, before their final maturation in the spleen, has not been elucidated. We show here that immature B cells fail to home to the lymph nodes. These cells can actively exclude themselves from antigen-enriched sites by downregulating their integrin-mediated adhesion to the extracellular matrix protein, fibronectin. This inhibition is mediated by interferon gamma secretion. Perturbation of interferon gamma activity in vivo leads to the homing of immature B cells to the lymph nodes. This is the first example of autocrine regulation of immune cell migration to sites of foreign antigen presentation. PMID:11067886

  7. Novel mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infections

    DEFF Research Database (Denmark)

    Storgaard, M; Varming, K; Herlin, Troels;

    2006-01-01

    In 1981 we presented a patient with Mycobacterium intracellulare osteomyelitis and depressed monocyte cytotoxicity. It is now demonstrated that the molecular defect was a never-before-described nucleotide deletion at position 794 (794delT) in the interferon-gamma-receptor alpha-1 gene. The genetic...... defect was passed on to his daughter who was diagnosed with non-tuberculous mycobacterial osteomyelitis at the age of 7 years....

  8. 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

  9. 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.

  10. Gamma Interferon (IFN-γ) Receptor Restricts Systemic Dengue Virus Replication and Prevents Paralysis in IFN-α/β Receptor-Deficient Mice

    OpenAIRE

    Prestwood, Tyler R.; Morar, Malika M.; Zellweger, Raphaël M.; Miller, Robyn; May, Monica M.; Yauch, Lauren E.; Lada, Steven M.; Shresta, Sujan

    2012-01-01

    We previously reported that mice lacking alpha/beta and gamma interferon receptors (IFN-α/βR and -γR) uniformly exhibit paralysis following infection with the dengue virus (DENV) clinical isolate PL046, while only a subset of mice lacking the IFN-γR alone and virtually no mice lacking the IFN-α/βR alone develop paralysis. Here, using a mouse-passaged variant of PL046, strain S221, we show that in the absence of the IFN-α/βR, signaling through the IFN-γR confers approximately 140-fold greater ...

  11. Improvement of interferon-beta related skin reactions after diluent halving: first experience of five patients

    OpenAIRE

    Zecca C; Yawalkar N; Gobbi C

    2012-01-01

    Chiara Zecca,1 Nikhil Yawalkar,2 Claudio Gobbi11Neurocenter of Southern Switzerland, Lugano, 2Department of Dermatology, Bern University Hospital, Bern, SwitzerlandBackground: The spectrum of side effects related to interferon beta-1b (INF-1b) treatment may compromise long-term adherence.Methods: Five INF-1b-treated multiple sclerosis patients with poor skin tolerability and clinical stability were instructed to dissolve the established (250 µg) INF-1b dose in half (0.5 mL) the stan...

  12. Chemokine receptor expression on B cells and effect of interferon-beta in multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Roed, Hanne; Sellebjerg, Finn

    2002-01-01

    We investigated the B-cell expression of chemokine receptors CXCR3, CXCR5 and CCR5 in the blood and cerebrospinal fluid (CSF) from patients in relapse of multiple sclerosis (MS) and in neurological controls. Chemokine receptor expression was also studied in interferon-beta-treated patients...... with relapsing-remitting or secondary progressive MS. We observed significantly higher expression of CXCR3 on B cells in the CSF in active MS than in controls. Patients with active MS also had higher B-cell expression of CCR5 in blood. No major differences between RRMS and SPMS patients were detected...

  13. 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

  14. Gamma interferon and 5-azacytidine cause transcriptional elevation of class I major histocompatibility complex gene expression in K562 leukemia cells in the absence of differentiation.

    Science.gov (United States)

    Chen, E; Karr, R W; Frost, J P; Gonwa, T A; Ginder, G D

    1986-05-01

    We studied the effects of gamma interferon (IFN-gamma) on HLA class I gene expression, differentiation, and proliferative capacity of K562 human leukemia cells. In the uninduced state, K562 cells show little or no class I gene expression but actively express the erythroid-specific gamma-globin gene as well as genes associated with cell proliferation, including the transferrin receptor, c-myc, and alpha-actin genes At both the surface protein and mRNA levels, IFN-gamma induces class I and beta 2-microglobulin gene expression, but does not alter the expression of the gamma-globin, transferrin receptor, c-myc, or alpha-actin genes. A 10-fold maximal induction of both class I surface protein and mRNA occurs at 48 h and is reversible upon withdrawal of IFN-gamma from the culture medium. In vitro nuclear run-on transcription assays were performed to directly establish that IFN-gamma exerts an early effect at the level of transcription, with maximal transcription rates occurring within 4 h. The difference between the time course of transcription induction and that of mRNA accumulation suggests that the regulation of class I gene expression in this human leukemic cell line also involves posttranscriptional mechanisms. Measurements of cell proliferation rates and cell cycle distribution, as well as the reversibility of the effects of IFN-gamma, demonstrate that the selective induction of class I genes in these cells occurs in the absence of differentiation.

  15. Mechanism of interferon-gamma-induced increase in T84 intestinal epithelial tight junction.

    Science.gov (United States)

    Boivin, Michel A; Roy, Praveen K; Bradley, Angela; Kennedy, John C; Rihani, Tuhama; Ma, Thomas Y

    2009-01-01

    Interferon-gamma (IFN-gamma) is an important proinflammatory cytokine that plays a central role in the intestinal inflammatory process of inflammatory bowel disease. IFN-gamma induced disturbance of the intestinal epithelial tight junction (TJ) barrier has been postulated to be an important mechanism contributing to intestinal inflammation. The intracellular mechanisms that mediate the IFN-gamma induced increase in intestinal TJ permeability remain unclear. The aim of this study was to examine the role of the phosphatidylinositol 3-kinase (PI3-K) pathway in the regulation of the IFN-gamma induced increase in intestinal TJ permeability using the T84 intestinal epithelial cell line. IFN-gamma caused an increase in T84 intestinal epithelial TJ permeability and depletion of TJ protein, occludin. The IFN-gamma induced increase in TJ permeability and alteration in occludin protein was associated with rapid activation of PI3-K; and inhibition of PI3-K activation prevented the IFN-gamma induced effects. IFN-gamma also caused a delayed but more prolonged activation of nuclear factor-kappaB (NF-kappaB); inhibition of NF-kappaB also prevented the increase in T84 TJ permeability and alteration in occludin expression. The IFN-gamma induced activation of NF-kappaB was mediated by a cross-talk with PI3-K pathway. In conclusion, the IFN-gamma induced increase in T84 TJ permeability and alteration in occludin protein expression were mediated by the PI3-K pathway. These results show for the first time that the IFN-gamma modulation of TJ protein and TJ barrier function is regulated by a cross-talk between PI3-K and NF-kappaB pathways. PMID:19128033

  16. 4. pi beta. -. gamma. coincidence system with minimally broadened pulses

    Energy Technology Data Exchange (ETDEWEB)

    Gehrke, R.J.; Johnson, L.O. (Idaho National Engineering Lab., Idaho Falls (USA))

    1982-12-15

    The performance characteristics of a new type 4..pi.. ..beta..-..gamma.. coincidence system have been measured. In contrast with the conventional 4..pi.. ..beta..-..gamma.. circuitry, which is based on a fixed pulse width (approx.= 2 ..mu..s) and a non-extendable dead time, the pulse processing circuitry in this new system is based on a minimally broadened pulse (i.e., as narrow as 0.25 ..mu..s). In this system each pulse has a different pulse width, so that the dead times for the ..beta..- and ..gamma..-ray detectors are determined by summing the measured dead time attributed by each pulse in each channel. The ..beta..-..gamma.. coincidences are defined with an overlap coincidence circuit. This system is shown to be much less sensitive to mismatch in the coincidence timing than is the conventional system. In spite of the narrower pulse widths, no spurious ..beta.. pulses are observed when the 4..pi.. proportional counter is operated near the center of its plateau. Disintegration rates were measured for calibrated sources with strength up to approx.= 10/sup 6/ Bq. These data indicate that with this new system the disintegration rates of very intense sources (approx.= 10/sup 6/ Bq) and moderately intense sources (< 10/sup 5/ Bq) can be determined with accuracies of approx.= 4% and <= 0.1%, respectively.

  17. Interferon Gamma Release Assays in active Tuberculosis: new medical insights

    Directory of Open Access Journals (Sweden)

    Sandro Pierdomenico

    2011-09-01

    Full Text Available Since first presentation, Interferon γ Release Assays (IGRAs have had basic and wide application to LTBI, in accordance with international consensus and CDC recommendations, leaving their use in active TB to the field of study and research.We reviewed the results of 633 patients investigated from 2004 to 2008 targeting active TB, with the objective to highlight immunological data supporting test performances.We evaluated Quantiferon TB Gold (1st generation IGRA kit in association to Culture (MGIT 960 and Lowenstein Jensen and PCR (Probetec-ET having the positivity of culture plus clinical diagnosis as the standard true value to compare. QTB Gold was studied in 69 TB positive patients (42 pulmonary and 27 extra-pulmonary, with Sensitivity, Specificity, PPV and NPV average to 61.8%, 94.5%, 54.3% and 95.9% respectively, after indeterminate results discharging. Significant statistical differences didn’t emerge between pulmonary and extra-pulmonary infections (CI 95%.The overall indeterminate ratio arose up to 20.3% in patients with active TB vs 2.7% of global population (p<0.001. In 22% of patients with active pulmonary disease, IGRA conversed to positivity after 15 days in replicated tests, in spite of current treatment. 4 patients, with pulmonary TB and Quantiferon persistent negativities, underwent 18 months follow-up as not respondent although SIRE phenotypic susceptibilities and enough DOT compliance. Molecular DST documented hetero resistance for rpoB (MUT 1, MUT 3 plus wild lines and katG (MUT 1 plus wild in association to lack of inhA wild lines (Genotype MTBDR plus, Hain Lifescience. These reports suggest a mutational relationship between Rv3874 – 3875 cassette, encoding ESAT-6 / CFP-10, and rpoB, katG, inhA genes plausibly implying weak or absent selective clonal Th 1 activation to IGRA antigens. Our data seem to point out: 1 positive results are able to match true active TB in less than 50% of patients; 2 negative results could leave

  18. Host Interferon-Gamma Inducible Protein Contributes to Brucella Survival

    Directory of Open Access Journals (Sweden)

    Jennifer eRitchie

    2012-04-01

    Full Text Available Brucella spp. are highly adapted intracellular pathogens of mammals that cause chronic infections while surving and replicating in host monocytes and macrophages. Although monocytes are normally susceptible to infection, pretreatment with pro-inflammatory cytokine interferon- (IFN- activates cellular defense mechanisms that increase intracellular killing of Brucella and prevents bacterial replication. We examined the contribution of the IFN- inducible GTPase, LRG-47, to B. abortus 2308 infection in in vitro and in vivo murine models. Infecting nonactivated macrophages from LRG-47-/- mice revealed that loss of this host protein negatively effected the intracellular survival and replication of IgG opsonized B. abortus. In contrast, survival and replication of non-opsonized B. abortus was the same in both C57/B6 and LRG-47-/- peritoneal macrophages. Following IFN-γ activation of LRG-47-/- monocytes, IgG opsonized B. abortus survived better than non-opsonized bacteria. Similar experiments using macrophages from BALB/c and C57/B6 mice found no difference in intracellular survival or replication between non-opsonized and IgG opsonized B. abortus in either resting or IFN-γ activated monocytes. The differential fate of opsonized and non-opsonized B. abortus was only observed in macrophages collected from LRG-47-/- mice. Given the specific nature of the relationship between this host protein and the mechanism of Brucella internalization, LRG-47-/- mice were infected with B. abortus to assess whether the loss of the lrg47 protein would affect the ability of the bacteria to colonize or persist within the host. B. abortus were able to establish and maintain similar numbers of bacteria in both C57/B6 mice and LRG-47-/- through 3 weeks post intraperitoneal infection. By nine weeks p.i. fewer B. abortus were recovered from LRG-47-/- mice than controls, suggesting that the host protein has a positive role in maintaining long term persistence of the

  19. Interferon

    CERN Document Server

    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.

  20. Hyper-beta-alaninemia associated with beta-aminoaciduria and gamma-aminobutyricaciduaia, somnolence and seizures.

    Science.gov (United States)

    Scriver, C R; Pueschel, S; Davies, E

    1966-03-24

    Hyper-beta-alaninemia was found in a somnolent, convulsing infant. Hyper-beta-aminoaciduria (beta-ala, betaAIB and taurine) was also observed, varying directly with plasma beta-alanine concentration. The beta-aminoaciduria is explained by the interaction between beta-alanine and a specific cellular-transport system with preference for beta-amino compounds. Gamma-aminobutyricaciduria was also observed, its excretion being independent of beta-alanine levels. Dietary modifications, pyridoxine, pantothenic acid and antibiotic therapy were not beneficial. Post-mortem tissues had elevated levels of beta-alanine and carnosine; GABA levels in brain were probably elevated for the age of the patient. A proposed block in beta-alanine-alpha-ketoglutarate transaminase would expand the free beta-alanine pool, thus increasing tissue carnosine. beta-Alanine is a central-nervous-system depressant. Associated inhibition of GABA transaminase and displacement of GABA from central-nervous-system binding sites would produce GABAuria and convulsions. PMID:17926374

  1. 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.

  2. Clinical and diagnostic developments of a gamma interferon release assay for use in bovine tuberculosis control programs

    Science.gov (United States)

    Currently the Bovigam assay is used as an official supplemental test within the bovine tuberculosis eradication program. This assay measures interferon-gamma (IFN-gamma) produced by lymphocytes in response to specific antigens. The objectives of the present study were to evaluate two Mycobacterium ...

  3. 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....... The corresponding number of IFNbeta-regulated genes in NAb-positive patients was zero. CONCLUSION: In neutralizing antibody (NAb)-positive patients without an MxA response, we were not able to detect differential expression of any of the 1077 interferon (IFN) beta-regulated genes identified in NAb-negative patients...

  4. Immunogenicity of Recombinant Human Interferon Beta-1b in Immune-Tolerant Transgenic Mice Corresponds with the Biophysical Characteristics of Aggregates

    NARCIS (Netherlands)

    Haji Abdolvahab, Mohadeseh; Fazeli, Ahmad; Halim, Andhyk; Sediq, Ahmad S; Fazeli, Mohammad Reza; Schellekens, Huub

    2016-01-01

    Determining to what extent biophysical characteristics of aggregates affect immunogenicity of therapeutic interferon beta-1b. Three recombinant human interferon beta-1b (rhIFNβ-1b) samples with different levels of aggregates generated by copper oxidation, thermal stress, or left untreated, as well a

  5. Receptor density is key to the alpha2/beta interferon differential activities.

    Science.gov (United States)

    Moraga, Ignacio; Harari, Daniel; Schreiber, Gideon; Uzé, Gilles; Pellegrini, Sandra

    2009-09-01

    Multiple type I interferons (IFN-alpha/beta) elicit Jak/Stat activation, rapid gene induction, and pleiotropic effects, such as differentiation, antiviral protection, and blocks in proliferation, which are dependent on the IFN subtype and the cellular context. To date, ligand- and receptor-specific molecular determinants underlying IFN-alpha/beta differential activities or potencies have been well characterized. To analyze cellular determinants that impact subtype-specific potency, human fibrosarcoma U5A-derived clones, exhibiting a gradient of IFN sensitivity by virtue of increasing receptor levels, were monitored for Jak/Stat signaling, gene induction, cell cycle lengthening, and apoptosis. In cells with scarce receptors, IFN-beta was more potent than IFN-alpha2 in antiproliferative activity, while the two subtypes were equipotent in all other readouts. Conversely, in cells with abundant receptors, IFN-alpha2 matched or even surpassed IFN-beta in all readouts tested. Our results suggest that the differential activities of the IFN subtypes are dictated not only by the intrinsic ligand/receptor binding kinetics but also by the density of cell surface receptor components.

  6. Fênomeno de Raynaud grave associado a terapia com interferon-beta para esclerose múltipla: relato de caso

    OpenAIRE

    CRUZ BORIS AFONSO; QUEIROZ EUSTÁQUIO DE; SIMONE VILELA NUNESi; CRUZ FILHO ACHILES; CAMPOS GILBERTO BELISARIO; MONTEIRO ERNESTO LENTZ DE CARVALHO; CRIVELLARI HUMBERTO

    2000-01-01

    Interferon-B (IFN-beta) é usado no tratamento de esclerose múltipla (EM). Descrevemos o caso de uma mulher com EM que apresentou fenômeno de Raynaud grave, livedo reticular e necrose digital duas semanas após tratamento com IFN-beta. Os sintomas melhoraram após suspensão do IFN-beta e início de anticoagulação associada a ciclofosfamida e corticóide. Fenômeno de Raynaud é um efeito colateral provável da terapia com IFN-beta para EM.

  7. Fênomeno de Raynaud grave associado a terapia com interferon-beta para esclerose múltipla: relato de caso Severe Raynaud's phenomenon associated with interferon-beta therapy for multiple sclerosis: case report

    Directory of Open Access Journals (Sweden)

    BORIS AFONSO CRUZ

    2000-06-01

    Full Text Available Interferon-B (IFN-beta é usado no tratamento de esclerose múltipla (EM. Descrevemos o caso de uma mulher com EM que apresentou fenômeno de Raynaud grave, livedo reticular e necrose digital duas semanas após tratamento com IFN-beta. Os sintomas melhoraram após suspensão do IFN-beta e início de anticoagulação associada a ciclofosfamida e corticóide. Fenômeno de Raynaud é um efeito colateral provável da terapia com IFN-beta para EM.Interferon-beta (IFN-beta is administered for treatment of multiple sclerosis (MS. We report on a woman with MS who presented with severe Raynaud's phenomenon, livedo-reticularis and digital necrosis two weeks after beginning therapy with IFN-beta. Symptoms improved after the IFN-beta was discontinued and anticoagulation associated with cyclophosphamide and corticoid were introduced. Raynaud's phenomenon is probably a side effect of IFN-beta therapy for multiple sclerosis.

  8. Interferon beta 1-a na esclerose múltipla: experiência de um ano em 62 pacientes Interferon beta 1-a in multiple sclerosis: experience of one year in 62 patients

    Directory of Open Access Journals (Sweden)

    CHARLES P. TILBERY

    2000-06-01

    Full Text Available Relatamos os resultados de estudo com o interferon beta 1-a em 62 pacientes ambulatoriais com a forma remitente-recorrente da esclerose múltipla durante um ano. Os critérios de inclusão para este tratamento foram de escore do EDSS entre 0 e 5,5 e de pelo menos relato de dois surtos nos dois últimos anos. Administramos 3 milhões de unidades internacionais de interferon beta 1-a três vezes por semana. Os objetivos deste estudo foram verificar o efeito da medicação no número de surtos e avaliar a eficácia da droga na progressão da doença. O índice anual de surtos nos pacientes que não tomaram a medicação foi 1,32 e naqueles medicados 0,63. O escore do EDSS em pacientes não medicados foi 4,7 e naqueles com medicamento 2,0. O interferon beta 1-a foi bem tolerado e 85% dos pacientes completaram um ano de tratamento.We report the results of a trial of interferon beta 1-a in 62 ambulatory patients with relapsing-remitting multiple sclerosis. Entry criteria included EDSS of 0 to 5.5 and at least two exacerbations in the previous 2 years. The patients received 3 million international units by subcutaneous injections three times a week. The end points were differences in exacerbation rate and treatment effect on disease progression. The annual exacerbation rate for patients that did not take the interferon beta 1-a was 1.32 and for the patients under medication 0.63. The EDSS score in patients that did not take the mediaction was 4.7 and 2.0 for the patients with interferon beta 1-a. Interferon beta 1-a was well tolerated and 85% of patients completed 1 year treatment.

  9. Is the gamma interferon assay in cattle influenced by multiple tuberculin injections?

    OpenAIRE

    Rangen, Sheila A.; Surujballi, Om P.; Lutze-Wallace, Cyril; Lees, V. Wayne

    2009-01-01

    Along with other developed countries, Canada is interested in adopting the gamma interferon (IFN-γ) assay to test for bovine tuberculosis (TB). This study compared results of using the IFN-γ assay in a large number of field-tested cattle in Manitoba, some previously tested with a caudal fold test (CFT) only, and others injected with tuberculins for both a CFT and a comparative cervical test (CCT). Parallel testing further compared the IFN-γ assay and CCT results with the confirmed TB status o...

  10. Methylation status of the interferon-gamma gene promoter in chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective To evaluate the methylation status at CpG site -55 in the interferon-gamma (IFN-γ) gene promoter and its effect on IFN-γ expression in chronic hepatitis B. Method The authors recruited 30 patients with HBeAg-positive chronic hepatitis B (CHB), 30 HBeAg-negative CHB patients, and 30 healthy blood donors. Pyrosequencing was used to determine the methylation status at CpG site -55 in the IFN-γ gene promoter following bisulfite treatment of DNA in peripheral blood mononuclear cells (PBMCs). The expres...

  11. Gamma Interferon Signaling in Macrophage Lineage Cells Regulates Central Nervous System Inflammation and Chemokine Production ▿

    OpenAIRE

    Lin, Adora A.; Tripathi, Pulak K.; Sholl, Allyson; Jordan, Michael B.; Hildeman, David A.

    2009-01-01

    Intracranial (i.c.) infection of mice with lymphocytic choriomeningitis virus (LCMV) results in anorexic weight loss, mediated by T cells and gamma interferon (IFN-γ). Here, we assessed the role of CD4+ T cells and IFN-γ on immune cell recruitment and proinflammatory cytokine/chemokine production in the central nervous system (CNS) after i.c. LCMV infection. We found that T-cell-depleted mice had decreased recruitment of hematopoietic cells to the CNS and diminished levels of IFN-γ, CCL2 (MCP...

  12. [THE PERSPECTIVES OF STUDYING OF POLYMORPHISM OF GENES OF GAMMA-INTERFERON UNDER CHRONIC BRUCELLOSIS].

    Science.gov (United States)

    Nurpeisova, A Kh; Kolomeietz, A N

    2016-02-01

    The brucellosis is an actual zoonotic disease in many countries, Russia included. The complexity of individual prognosis of disease and choice of tactics of maintenance of patients is explained by heterogeneity of clinical manifestations of brucellosis and different rate of progression of organs pathology. Despite of low mortality, this pathology quite often results in disability of patient. The frequent transition of acute process into chronic one (40-60%), probability of development of primary chronic brucellosis determines interest of researchers to issues of immunopathogenesis of this disease. The article presents review of achievements in studies of polymorphism of genes of gamma-interferon in the given area.

  13. 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...

  14. Interferon Gamma Release Assays for Latent Tuberculosis: What Are the Sources of Variability?

    Science.gov (United States)

    Banaei, Niaz; Gaur, Rajiv L; Pai, Madhukar

    2016-04-01

    Interferon gamma release assays (IGRAs) are blood-based tests intended for diagnosis of latent tuberculosis infection (LTBI). IGRAs offer logistical advantages and are supposed to offer improved specificity over the tuberculin skin test (TST). However, recent serial testing studies of low-risk individuals have revealed higher false conversion rates with IGRAs than with TST. Reproducibility studies have identified various sources of variability that contribute to nonreproducible results. Sources of variability can be broadly classified as preanalytical, analytical, postanalytical, manufacturing, and immunological. In this minireview, we summarize known sources of variability and their impact on IGRA results. We also provide recommendations on how to minimize sources of IGRA variability. PMID:26763969

  15. 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 be developed. The enzyme-linked immunospot (ELISPOT) assay is a highly sensitive technique for the detection of cytokines and has the potential to improve the diagnosis of JD. Of the variables examined, choice of capture antibody and the method by which the peripheral blood mononuclear cells were isolated......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...

  16. Polymorphisms of innate pattern recognition receptors, response to interferon-beta and development of neutralizing antibodies in multiple sclerosis patients

    DEFF Research Database (Denmark)

    Enevold, Christian; Oturai, Annette Bang; Sørensen, Per Soelberg;

    2010-01-01

    Interferon-beta therapy of patients with relapsing-remitting multiple sclerosis involves repeated 'immunizations' with exogenous protein solutions. Innate pattern recognition receptors play an important role in immune responses towards foreign substances and may thus be related to treatment outcome....

  17. Can aerobic exercise alleviate flu-like symptoms following interferon beta-1a injections in patients with multiple sclerosis?

    DEFF Research Database (Denmark)

    Langeskov-Christensen, Martin; Kjølhede, Tue; Stenager, Egon;

    2016-01-01

    BACKGROUND: Flu-like symptoms (FLS) are common side effects of interferon beta (IFNß) treatment, and may affect the willingness to initiate therapy, the long-term acceptability, and the adherence to the treatment. Case reports suggest that aerobic exercise is able to markedly reduce FLS following...

  18. Selective suppression of chemokine receptor CXCR3 expression by interferon-beta1a in multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Sellebjerg, F

    2002-01-01

    We studied the expression of chemokine receptors CCR1, CCR2, CCR3, CCR5, and CXCR3 on CD4 and CD8 positive T cells, and on CD14 positive monocytes in blood from 10 patients with relapsing-remitting multiple sclerosis (MS) at initiation of interferon (IFN)-beta treatment, after 1 month and after 3...

  19. 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.

  20. 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.

  1. 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...

  2. In Vivo Interrelationship between Insulin Resistance and Interferon Gamma Production: Protective and Therapeutic Effect of Berberine

    Science.gov (United States)

    Sahyoun, Heba Abdelghany; Elshehawy, Ashraf Abdelhamed; Elsayed, Mohammad Mohammad

    2016-01-01

    This research was conducted to investigate if there is a relation between insulin resistance incidence and inhibition of interferon gamma production or not. Firstly, insulin resistance was induced by high fat diet (HFD) intake for 6 weeks. Secondly, berberine was used as protective/curative compound for insulin resistance. Results revealed that feeding rats HFD for 6 weeks developed features of insulin resistance (IR) syndrome. These features presented in increased body weight, hyperglycemia, hyperinsulinemia, hypercholesterolemia (with increased LDL-cholesterol and decreased HDL-cholesterol), and hypertriglyceridemia. Level of antioxidant enzymes in HFD group was higher than in normal one. Also there was an increasing in level of proinflammatory cytokines as interleukin- (IL-) 6 and IL-12 in HFD group. Feeding rats HFD for 6 weeks also decreased level of interferon gamma (IFN-γ). The decreased level of IFN-γ has been shown to predict infection with infectious diseases especially viral infection. Treatment and protection with berberine 50 mg/kg/day for 2 weeks were found to be effective against the features of insulin resistance syndrome, improved levels of insulin resistance parameters, lipid profile, antioxidant enzymes, proinflammatory cytokines, and IFN-γ. PMID:27642351

  3. In Vivo Interrelationship between Insulin Resistance and Interferon Gamma Production: Protective and Therapeutic Effect of Berberine.

    Science.gov (United States)

    Mahmoud, Mohammad Ahmad; Ghareeb, Doaa Ahmad; Sahyoun, Heba Abdelghany; Elshehawy, Ashraf Abdelhamed; Elsayed, Mohammad Mohammad

    2016-01-01

    This research was conducted to investigate if there is a relation between insulin resistance incidence and inhibition of interferon gamma production or not. Firstly, insulin resistance was induced by high fat diet (HFD) intake for 6 weeks. Secondly, berberine was used as protective/curative compound for insulin resistance. Results revealed that feeding rats HFD for 6 weeks developed features of insulin resistance (IR) syndrome. These features presented in increased body weight, hyperglycemia, hyperinsulinemia, hypercholesterolemia (with increased LDL-cholesterol and decreased HDL-cholesterol), and hypertriglyceridemia. Level of antioxidant enzymes in HFD group was higher than in normal one. Also there was an increasing in level of proinflammatory cytokines as interleukin- (IL-) 6 and IL-12 in HFD group. Feeding rats HFD for 6 weeks also decreased level of interferon gamma (IFN-γ). The decreased level of IFN-γ has been shown to predict infection with infectious diseases especially viral infection. Treatment and protection with berberine 50 mg/kg/day for 2 weeks were found to be effective against the features of insulin resistance syndrome, improved levels of insulin resistance parameters, lipid profile, antioxidant enzymes, proinflammatory cytokines, and IFN-γ. PMID:27642351

  4. 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.

  5. 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.

  6. High rate 4. pi. beta. -. gamma. coincidence counting system

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, L.O.; Gehrke, R.J.

    1978-01-01

    A high count rate 4..pi.. ..beta..-..gamma.. coincidence counting system for the determination of absolute disintegration rates of short half-life radionuclides is described. With this system the dead time per pulse is minimized by not stretching any pulses beyond the width necessary to satisfy overlap coincidence requirements. The equations used to correct for the ..beta.., ..gamma.., and coincidence channel dead times and for accidental coincidences are presented but not rigorously developed. Experimental results are presented for a decaying source of /sup 56/Mn initially at 2 x 10/sup 6/ d/s and a set of /sup 60/Co sources of accurately known source strengths varying from 10/sup 3/ to 2 x 10/sup 6/ d/s. A check of the accidental coincidence equation for the case of two independent sources with varying source strengths is presented.

  7. 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

    Interferon-beta (IFN-beta) therapy for multiple sclerosis (MS) is associated with a potential for induction of neutralizing antibodies (NAbs). Because immune reactivity depends on changes in lipoprotein metabolism, we investigated whether plasma lipoprotein profiles could be associated with the...... 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....

  8. Methylprednisolone does not restore biological response in multiple sclerosis patients with neutralizing antibodies against interferon-beta

    DEFF Research Database (Denmark)

    Hesse, D; Frederiksen, J L; Koch-Henriksen, N;

    2009-01-01

    Background and purpose: Neutralizing antibodies (NAbs) appearing during treatment with Interferon-beta (IFN-beta) reduce or abolish bioactivity and therapeutic efficacy. Initial combination therapy with methylprednisolone (MP) may reduce the frequency of NAb positive patients. We hypothesized that...... Resistance Protein A (MxA) mRNA induction in whole blood using real time PCR. Results: At the end of study, median NAb NC was 92% in both groups. Eight patients (21%) in the MP group and four patients (11%) in the control group had regained an in vivo MxA response to IFN-beta (P = 0.35). Conclusions: Monthly...

  9. 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

  10. Gamma and beta intra-operative imaging probes

    International Nuclear Information System (INIS)

    Small area (∝1.5 cm2) scintillation cameras for imaging gammas and betas using inter-changeable detector front ends were built and characterized. Components common to both emission imaging cameras include: (1) fiber optic bundles 2-3 m long, comprised of multi-clad fibers which connect the scintillation detector to (2) an MC-PMT; (3) parallel MC-PMT outputs feed a resistive positioning network and i-V converter/line driver network which produce balanced +X, -X, +Y, and -Y outputs; and (4) four ADCs and a Macintosh PC for system control and image display. The beta and gamma devices used distinct scintillation detectors which were characterized by both simulation and measurement. The beta camera utilized a 0.5 mm by 1.25 cm φ CaF2(Eu) scintillation crystal coupled, through a diffusing light guide, to 19 2-mm φ optical fibers. These front-end fibers are in turn coupled by a more flexible fiber bundle to the MC-PMT. CaF2(Eu) has high light output, high beta sensitivity, and low gamma sensitivity. Image signals are histogrammed and displayed after Anger logic computations are performed on digitized signals. The beta camera has 2 and 2 x 2 mm2 CsI(Tl) and NaI(Tl) crystals of various lengths, and 3 mm thick continuous crystals. Configurations using 4 x 4 element matrices with one-to-one coupling between crystals and fiber channels, and light diffusers between each crystal matrix and fibers were evaluated. (orig.)

  11. Untersuchung der Sicherheit und Verträglichkeit von Interferon-beta-1b bei Kindern und Jugendlichen mit Multipler Sklerose

    OpenAIRE

    Schelensky, Lilien

    2012-01-01

    Multiple sclerosis (MS) is the most common neurological disease of non-traumatic origin, which leads in young adulthood to permanent disability. 3-5% of patients experience the clinical onset of their disease in childhood and adolescence. The treatment of MS currently consists mainly in an immunemodulatory therapy with interferon beta-1a (INFß-1a, i.m. / s.c.), interferon beta-1b (INFß-1b) or glatiramer acetate. For beta-interferons here the safety, tolerability and effectiveness, especially ...

  12. Use of Piezoelectric Immunosensors for Detection of Interferon-Gamma Interaction with Specific Antibodies in the Presence of Released-Active Forms of Antibodies to Interferon-Gamma

    Directory of Open Access Journals (Sweden)

    Elena Don

    2016-01-01

    Full Text Available In preliminary ELISA studies where released-active forms (RAF of antibodies (Abs to interferon-gamma (IFNg were added to the antigen-antibody system, a statistically significant difference in absorbance signals obtained in their presence in comparison to placebo was observed. A piezoelectric immunosensor assay was developed to support these data and investigate the effects of RAF Abs to IFNg on the specific interaction between Abs to IFNg and IFNg. The experimental conditions were designed and optimal electrode coating, detection circumstances and suitable chaotropic agents for electrode regeneration were selected. The developed technique was found to provide high repeatability, intermediate precision and specificity. The difference between the analytical signals of RAF Ab samples and those of the placebo was up to 50.8%, whereas the difference between non-specific controls and the placebo was within 5%–6%. Thus, the piezoelectric immunosensor as well as ELISA has the potential to be used for detecting the effects of RAF Abs to IFNg on the antigen-antibody interaction, which might be the result of RAF’s ability to modify the affinity of IFNg to specific/related Abs.

  13. Use of Piezoelectric Immunosensors for Detection of Interferon-Gamma Interaction with Specific Antibodies in the Presence of Released-Active Forms of Antibodies to Interferon-Gamma.

    Science.gov (United States)

    Don, Elena; Farafonova, Olga; Pokhil, Suzanna; Barykina, Darya; Nikiforova, Marina; Shulga, Darya; Borshcheva, Alena; Tarasov, Sergey; Ermolaeva, Tatyana; Epstein, Oleg

    2016-01-01

    In preliminary ELISA studies where released-active forms (RAF) of antibodies (Abs) to interferon-gamma (IFNg) were added to the antigen-antibody system, a statistically significant difference in absorbance signals obtained in their presence in comparison to placebo was observed. A piezoelectric immunosensor assay was developed to support these data and investigate the effects of RAF Abs to IFNg on the specific interaction between Abs to IFNg and IFNg. The experimental conditions were designed and optimal electrode coating, detection circumstances and suitable chaotropic agents for electrode regeneration were selected. The developed technique was found to provide high repeatability, intermediate precision and specificity. The difference between the analytical signals of RAF Ab samples and those of the placebo was up to 50.8%, whereas the difference between non-specific controls and the placebo was within 5%-6%. Thus, the piezoelectric immunosensor as well as ELISA has the potential to be used for detecting the effects of RAF Abs to IFNg on the antigen-antibody interaction, which might be the result of RAF's ability to modify the affinity of IFNg to specific/related Abs. PMID:26791304

  14. 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)

  15. Requirements for CD4+ cells and gamma interferon in resolution of established Cryptosporidium parvum infection in mice.

    OpenAIRE

    W. Chen; Harp, J A; Harmsen, A G

    1993-01-01

    The importance of CD4+ cells and gamma interferon (IFN-gamma) in the resolution of established Cryptosporidium parvum infection was investigated with a murine model of cryptosporidiosis in severe combined immunodeficient (SCID) mice. C. parvum-infected SCID mice were reconstituted with spleen cells from immunocompetent donors. The recipients were able to resolve their C. parvum infection by 17 days postreconstitution. Treatment of reconstituted SCID mice with either anti-CD4 monoclonal antibo...

  16. Gamma interferon-mediated increase in the number of Ia-bearing macrophages during infection with Listeria monocytogenes.

    OpenAIRE

    Koga, T.; Mitsuyama, M; Handa, T.; Watanabe, Y.; Nomoto, K.

    1987-01-01

    The role of gamma interferon (IFN-gamma) in an increase in Ia-bearing macrophages during Listeria monocytogenes infection was studied. The peritoneal macrophages from L. monocytogenes-infected mice contained a high proportion of Ia. Intraperitoneal injection of the supernatant from a culture of spleen cells from L. monocytogenes-infected mice induced Ia-rich exudates in normal mice. The Ia-inducing activity in the culture supernatant was abrogated by the pretreatment of spleen cells with anti...

  17. Porcine Interferon Gamma Promotes a Protective Innate Immune Response Against Foot-and-Mouth Disease in Swine

    Science.gov (United States)

    We have recently demonstrated that the synergistic action of type I and II interferons (IFN) can rapidly protect swine against challenge with a low dose of foot-and-mouth disease virus (FMDV). While we did not detect antiviral activity or the presence of IFN alpha or gamma in any of the protected an...

  18. Serum interferon-gamma is associated with longitudinal decline in lung function among asthmatic patients : the Normative Aging Study

    NARCIS (Netherlands)

    Litonjua, AA; Sparrow, D; Guevarra, L; O'Connor, GT; Weiss, ST; Tollerud, DJ

    2003-01-01

    Background: Cytokines are important mediators of the asthmatic response. A retrospective pilot study showed that serum levels of interleukin (IL)-5 and interferon (IFN)-gamma were related to lung function decline among asthmatic patients over the preceding 3 years. To confirm these findings, we test

  19. Comparison of interferon-gamma release assays and adenosine deaminase of pleural fluid for the diagnosis of pleural tuberculosis

    Institute of Scientific and Technical Information of China (English)

    刘菲

    2014-01-01

    Objective To compare the diagnostic performance of interferon gamma releasing assays(T-SPOT.TB)and adenosine deaminase(ADA)in pleural tuberculosis,and therefore to evaluate the value of T-SPOT.TB in a high tuberculosis burden country.Methods From June 2011to November 2012,111 patients with pleural fluid in Beijing Chest Hospital,Capital Medical University were

  20. 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...

  1. Targeting of Interferon Gamma to Stromal Fibroblasts Using a PDGF Receptor Recognizing Carrier Reduces Tumour Growth in Vivo

    NARCIS (Netherlands)

    Prakash, J.; Bansal, R.; Tomar, T.; Ostman, A.; Poelstra, K.

    2011-01-01

    Background: Stromal fibroblasts are the key cell types in tumour stroma, that support angiogenesis, tumour cell proliferation and metastasis. Therefore, inhibition of stromal fibroblasts activity might inhibit tumour growth. Interferon gamma (IFNγ) is a potent cytokine and has been used for the trea

  2. Vector-mediated expression of interferon gamma inhibits replication of hepatitis B virus in vitro.

    Science.gov (United States)

    Kan, Q C; Li, D L; Yu, Z J

    2013-01-01

    Despite the existence of efficient vaccines against hepatitis B virus (HBV) infections, these still represent a serious threat to human health worldwide. Acute HBV infections often become chronic, marked by liver cirrhosis and hepatocellular carcinoma. Promising results with interferons alpha or gamma (IFN-α, γ) or nucleoside/nucleotide analogs in inhibiting HBV replication in vitro have led to therapeutic applications to chronic HBV patients, however, their results so far have not been satisfactory. The treatments were either not effective in all patients or had adverse effects. Certain progress was expected from expression of interferons targeted to liver by adenovirus vectors, however, this approach turned out to be limited by undesired expression of toxic viral genes and high production costs. Therefore, in this study, we attempted to inhibit HBV replication in HepG2.2.15 cells by human IFN-γ expressed through a non-viral vector, an eukaryotic plasmid. The results demonstrated that IFN-γ, targeted to HBV-replicating cells, significantly inhibited the virus growth without inducing apoptosis and indicated that local expression of this kind of cytokine may be a promising strategy of gene therapy. PMID:24294955

  3. Interferon gamma response to Mycobacterium avium subsp. paratuberculosis specific lipopentapeptide antigen L5P in cattle.

    Science.gov (United States)

    Holbert, Sébastien; Branger, Maxime; Souriau, Armel; Lamoureux, Bérénice; Ganneau, Christelle; Richard, Gaëlle; Cochard, Thierry; Tholoniat, Christophe; Bay, Sylvie; Winter, Nathalie; Moyen, Jean Louis; Biet, Franck

    2015-10-01

    After Mycobacterium avium subsp. paratuberculosis (Map) infection the cell-mediated immune (CMI) response indicative of early Th1 activation may be detected using interferon-gamma release assay (IGRA). Currently, the purified protein derivatives (PPDs), i.e., the total extract of mycobacteria antigens are used to recall CMI responses against Map. This study aimed to assess the ability of the chemically synthesized Map specific cell wall lipopentapeptide L5P to induce CMI response in cows infected by Map compared to PPD. L5P and PPD elicited an IFN-γ response in 12 and 35 animals from two Map infected herds respectively, but IFN-γ was not detected in the 13 cows recruited from a non-infected herd. Levels of IFN-γ detected were higher with PPD than with L5P. There was no correlation between the IFN-γ response and the humoral response to Map or faecal culture. PMID:26412530

  4. Steroid receptor coactivator 1 links the steroid and interferon gamma response pathways.

    Science.gov (United States)

    Tzortzakaki, Eleni; Spilianakis, Charalambos; Zika, Eleni; Kretsovali, Androniki; Papamatheakis, Joseph

    2003-12-01

    We show here that steroid receptor coactivator 1 (SRC-1) is a coactivator of MHC class II genes that stimulates their interferon gamma (IFNgamma) and class II transactivator (CIITA)-mediated expression. SRC-1 interacts physically with the N-terminal activation domain of CIITA through two regions: one central [extending from amino acids (aa) 360-839] that contains the nuclear receptors binding region and one C-terminal (aa 1138-1441) that contains the activation domain 2. Using chromatin immunoprecipitation assays we show that SRC-1 recruitment on the class II promoter is enhanced upon IFNgamma stimulation. Most importantly, SRC-1 relieves the inhibitory action of estrogens on the IFNgamma-mediated induction of class II genes in transient transfection assays. We provide evidence that inhibition by estradiol is due to multiple events such as slightly reduced recruitment of CIITA and SRC-1 and severely inhibited assembly of the preinitiation complex.

  5. 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...... bovine IL-12 to the PPDj stimulation of blood samples from the heifer group in more than 20 Danish dairy herds which also perform surveillance of MAP antibodies in milk have been performed. The results indicate that IFN-γ assay results are specific for paratuberculosis, but the IFN-γ assay result...... rational in-herd management procedures and in the establishment of paratuberculosis status of a given herd. Indeed, for any diagnostic test applied in paratuberculosis, both the diagnostic target condition and the purpose of the diagnostic testing must be considered before any meaningful estimates...

  6. The Therapeutic Effect of Gamma Interferon in Chronic Bronchiolitis Due to Mustard Gas

    Directory of Open Access Journals (Sweden)

    Yunes Panahi

    2005-06-01

    In the two groups, FEV1 did not have statistical differences at base line (49.3±2.9 and 48.7±4.1, respectively, p = 0.6, whereas after treatment the data for FEV1 showed a significant increase in the case group (66.3±5.4 when compared with those in the control group (57.3±8.6, p=0.001. The findings of this study indicate that a 6-month treatment with interferon gamma -1b plus a low-dose of prednisolone is associated with the improvement of the lung function in mustard gas exposed patients with bronchiolitis

  7. Interferon Gamma: Influence on Neural Stem Cell Function in Neurodegenerative and Neuroinflammatory Disease

    Science.gov (United States)

    Kulkarni, Apurva; Ganesan, Priya; O’Donnell, Lauren A.

    2016-01-01

    Interferon-gamma (IFNγ), a pleiotropic cytokine, is expressed in diverse neurodegenerative and neuroinflammatory conditions. Its protective mechanisms are well documented during viral infections in the brain, where IFNγ mediates non-cytolytic viral control in infected neurons. However, IFNγ also plays both protective and pathological roles in other central nervous system (CNS) diseases. Of the many neural cells that respond to IFNγ, neural stem/progenitor cells (NSPCs), the only pluripotent cells in the developing and adult brain, are often altered during CNS insults. Recent studies highlight the complex effects of IFNγ on NSPC activity in neurodegenerative diseases. However, the mechanisms that mediate these effects, and the eventual outcomes for the host, are still being explored. Here, we review the effects of IFNγ on NSPC activity during different pathological insults. An improved understanding of the role of IFNγ would provide insight into the impact of immune responses on the progression and resolution of neurodegenerative diseases.

  8. 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

  9. 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...

  10. 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.

  11. Interferon gamma is involved in the recovery of athymic nude mice from recombinant vaccinia virus/interleukin 2 infection

    OpenAIRE

    1990-01-01

    Athymic nude mice recover from an infection with recombinant vaccinia virus (VV) encoding murine interleukin 2 (IL-2), but treatment with a mAb to IL-2 accentuated infection. Administration of a mAb against interferon gamma (IFN-gamma) to mice infected with the IL-2-encoding virus completely prevented the IL-2-induced mechanisms of recovery. Both asialo-GM1+ (NK) and asialo-GM1- (non-NK) cells were participants in the IFN-gamma-mediated recovery of nude mice from infection with the IL-2-encod...

  12. Inhibition of interferon gamma induced interleukin 12 production: a potential mechanism for the anti-inflammatory activities of tumor necrosis factor.

    Science.gov (United States)

    Hodge-Dufour, J; Marino, M W; Horton, M R; Jungbluth, A; Burdick, M D; Strieter, R M; Noble, P W; Hunter, C A; Puré, E

    1998-11-10

    Inflammation is associated with production of cytokines and chemokines that recruit and activate inflammatory cells. Interleukin (IL) 12 produced by macrophages in response to various stimuli is a potent inducer of interferon (IFN) gamma production. IFN-gamma, in turn, markedly enhances IL-12 production. Although the immune response is typically self-limiting, the mechanisms involved are unclear. We demonstrate that IFN-gamma inhibits production of chemokines (macrophage inflammatory proteins MIP-1alpha and MIP-1beta). Furthermore, pre-exposure to tumor necrosis factor (TNF) inhibited IFN-gamma priming for production of high levels of IL-12 by macrophages in vitro. Inhibition of IL-12 by TNF can be mediated by both IL-10-dependent and IL-10-independent mechanisms. To determine whether TNF inhibition of IFN-gamma-induced IL-12 production contributed to the resolution of an inflammatory response in vivo, the response of TNF+/+ and TNF-/- mice injected with Corynebacterium parvum were compared. TNF-/- mice developed a delayed, but vigorous, inflammatory response leading to death, whereas TNF+/+ mice exhibited a prompt response that resolved. Serum IL-12 levels were elevated 3-fold in C. parvum-treated TNF-/- mice compared with TNF+/+ mice. Treatment with a neutralizing anti-IL-12 antibody led to resolution of the response to C. parvum in TNF-/- mice. We conclude that the role of TNF in limiting the extent and duration of inflammatory responses in vivo involves its capacity to regulate macrophage IL-12 production. IFN-gamma inhibition of chemokine production and inhibition of IFN-gamma-induced IL-12 production by TNF provide potential mechanisms by which these cytokines can exert anti-inflammatory/repair function(s). PMID:9811882

  13. 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.

  14. Neutron-gamma competition for $\\beta$-delayed neutron emission

    CERN Document Server

    Mumpower, Matthew; Moller, Peter

    2016-01-01

    We present a coupled Quasi-particle Random Phase Approximation and Hauser-Feshbach (QRPA+HF) model for calculating delayed particle emission. This approach uses microscopic nuclear structure information which starts with Gamow-Teller strength distributions in the daughter nucleus, and then follows the statistical decay until the initial available excitation energy is exhausted. Explicitly included at each particle emission stage is $\\gamma$-ray competition. We explore this model in the context of neutron emission of neutron-rich nuclei and find that neutron-gamma competition can lead to both increases and decreases in neutron emission probabilities, depending on the system considered. A second consequence of this formalism is a prediction of more neutrons on average being emitted after $\\beta$-decay for nuclei near the neutron dripline compared to models that do not consider the statistical decay.

  15. 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.

  16. Regulation of interferon gamma signaling by suppressors of cytokine signaling and regulatory T cells

    Directory of Open Access Journals (Sweden)

    Joseph eLarkin

    2013-12-01

    Full Text Available Regulatory T cells (Tregs play an indispensable role in the prevention of autoimmune disease, as interferon gamma (IFN mediated, lethal autoimmunity occurs (in both mice and humans in their absence. In addition, regulatory T cells have been implicated in preventing the onset of autoimmune and auto-inflammatory conditions associated with aberrant IFN signaling such as type 1 diabetes, lupus, and LPS mediated endotoxemia. Notably, suppressor of cytokine signaling 1 deficient (SOCS1-/- mice also succumb to a lethal auto-inflammatory disease, dominated by excessive IFN signaling and bearing similar disease course kinetics to Treg deficient mice. Moreover SOCS1 deficiency has been implicated in lupus progression, and increased susceptibility to LPS mediated endotoxemia. Although it has been established that Tregs and SOCS1 play a critical role in the regulation of IFN signaling, and the prevention of lethal auto-inflammatory disease, the role of Treg/SOCS1 cross-talk in the regulation of IFN signaling has been essentially unexplored. This is especially pertinent as recent publications have implicated a role of SOCS1 in the stability of peripheral Tregs. This review will examine the emerging research findings implicating a critical role of the intersection of the SOCS1 and Treg regulatory pathways in the control of IFN gamma signaling and immune system function.

  17. 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...... stimulation was performed on day-old samples. Denmark is free of bovine tuberculosis, but cross-reactivity with paraTB could be documented for cattle more than 14 months old in paraTB-infected herds compared with those in non - paraTB-infected herds. In both paraTB-free and paraTB-infected herds, false...

  18. Cotinine and interferon-gamma levels in pre-school children exposed to household tobacco smoke

    Directory of Open Access Journals (Sweden)

    Lina Kalalo

    2013-10-01

    Conclusion Cotinine is not related to the interferon-γ level in children exposed to tobacco smoke, however, the interferon-γ level in children with tobacco smoke exposure is lower than in the non-tobacco smoke exposure group.

  19. 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.

  20. A monoclonal lewis rat myocyte line that responds to interferon-gamma: responsiveness with the potential to influence subsequent interactions with the immune system.

    Science.gov (United States)

    Stegall, T; Krolick, K A

    2000-02-01

    In order to begin asking questions about immunopathology associated with the model of the neuromuscular disease experimental autoimmune myasthenia gravis, a monoclonal myocyte line, LE1, has been prepared from the Lewis rat. The LE1 myocyte clone was selected from among several clones produced based on its ease of maintenance in culture and for the stability of its phenotype, which is very similar to that reported for in vivo muscle and other cultured myocyte lines. Thus, LE1 cells were observed to produce, constitutively, the myocyte-associated neural cell adhesion molecule (CD56), the intracellular adhesion molecule (ICAM-1), and the acetylcholine receptor. LE1 cells were also observed to constitutively secrete relatively low levels of IL-6 and TGF-beta. Moreover, the LE1 cell line may be of use for predicting muscle responses to various immune mediators. For example, the inflammatory cytokine interferon-gamma (IFN-gamma) has been recently reported by others to play a role in experimental myasthenia gravis. Thus, it was of interest that LE1 cells could be activated by IFN-gamma to express increased levels of immunopathologically relevant membrane molecules such as ICAM-1 and Class II major histocompatibility molecules (i.e., RT-1B). PMID:10637097

  1. Alpha-interferon induces enhanced expression of HLA-ABC antigens and beta-2-microglobulin in vivo and in vitro in various subsets of human lymphoid cells

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Larsen, J K; Plesner, T;

    1987-01-01

    The effect of cloned alpha-interferon (alpha-IFN) on the in vitro and in vivo expression of HLA-ABC antigens and beta-2-microglobulin (beta-2-m) on subpopulations of human lymphoid cells was studied by flow cytometry. Mononuclear cells isolated from patients and cell cultures were labelled...

  2. Disability Progression After Switching from Natalizumab to Fingolimod or Interferon Beta/Glatiramer Acetate Therapies

    Science.gov (United States)

    Fox, Robert J.; Tyry, Tuula; Salter, Amber R.; Campagnolo, Denise

    2016-01-01

    Background: Physicians must weigh the benefits against the risk of progressive multifocal leukoencephalopathy (PML) in patients treated with natalizumab, especially beyond 2 years. However, disability progression associated with switching therapies versus continuing natalizumab therapy after 2 years has not been fully evaluated. Methods: In this retrospective analysis using the NARCOMS Registry, disability progression (Patient-Determined Disease Steps [PDDS] scale) and physical health-related quality of life (HRQOL) worsening (12-item Short Form Health Status Survey Physical Component Score [SF-12 PCS]) were compared between participants switching to fingolimod (n = 50) or interferon beta (IFNβ)/glatiramer acetate (GA) (n = 71) therapy and those continuing natalizumab (n = 406) after 2 years or more of treatment (median follow-up: natalizumab, 4 years; fingolimod, 4.5 years; IFNβ/GA, 5 years). Results: Participants continuing to take natalizumab had less disability progression (mean PDDS change: natalizumab, 0.3; fingolimod, 0.6; IFNβ/GA, 0.7; P = .0036), were less likely to report disability progression (proportion with PDDS increase: natalizumab, 31%; fingolimod, 46%; IFNβ/GA, 42%; P = .0296), and had less worsening in physical HRQOL (mean SF-12 PCS change: natalizumab, −1.4; fingolimod, −2.8; IFNβ/GA, −4.6; P = .0476) than those switching treatment. Conclusions: Although all medication groups exhibited some level of worsening, switching from natalizumab treatment after 2 years was associated with increased disability progression and worsening physical HRQOL. The risk of disability progression from disease activity and the risk of PML should be considered when making natalizumab treatment decisions. PMID:27803638

  3. Baseline Gene Expression Signatures in Monocytes from Multiple Sclerosis Patients Treated with Interferon-beta

    Science.gov (United States)

    Bustamante, Marta F.; Nurtdinov, Ramil N.; Río, Jordi; Montalban, Xavier; Comabella, Manuel

    2013-01-01

    Background A relatively large proportion of relapsing-remitting multiple sclerosis (RRMS) patients do not respond to interferon-beta (IFNb) treatment. In previous studies with peripheral blood mononuclear cells (PBMC), we identified a subgroup of IFNb non-responders that was characterized by a baseline over-expression of type I IFN inducible genes. Additional mechanistic experiments carried out in IFNb non-responders suggested a selective alteration of the type I IFN signaling pathway in the population of blood monocytes. Here, we aimed (i) to investigate whether the type I IFN signaling pathway is up-regulated in isolated monocytes from IFNb non-responders at baseline; and (ii) to search for additional biological pathways in this cell population that may be implicated in the response to IFNb treatment. Methods Twenty RRMS patients classified according to their clinical response to IFNb treatment and 10 healthy controls were included in the study. Monocytes were purified from PBMC obtained before treatment by cell sorting and the gene expression profiling was determined with oligonucleotide microarrays. Results and discussion Purified monocytes from IFNb non-responders were characterized by an over-expression of type I IFN responsive genes, which confirms the type I IFN signature in monocytes suggested from previous studies. Other relevant signaling pathways that were up-regulated in IFNb non-responders were related with the mitochondrial function and processes such as protein synthesis and antigen presentation, and together with the type I IFN signaling pathway, may also be playing roles in the response to IFNb. PMID:23637780

  4. Identification of risk factors associated with disclosure of false positive bovine tuberculosis reactors using the gamma-interferon (IFNγ) assay

    OpenAIRE

    Gormley, Eamonn; Doyle, Mairead B.; Duignan, Anthony; et al.

    2013-01-01

    The gamma-interferon assay (IFNγ) is often used as an ancillary diagnostic test alongside the tuberculin skin test in order to detect Mycobacterium bovis infected cattle. The performance of the IFNγ test has been evaluated in many countries worldwide and wider usage as a disease surveillance tool is constrained due to the relatively low and inconsistent specificity at a herd and area level. This results in disclosure of a higher proportion of false positive reactors when compared with the ski...

  5. Application and Interpretation of an Interferon-Gamma Release Assay: Results of an Audit in a Canadian Centre

    Directory of Open Access Journals (Sweden)

    Sopharat Vat

    2012-01-01

    Full Text Available BACKGROUND: Interferon-gamma release assays (IGRAs are newly approved for diagnosing latent tuberculosis infection (LTBI. An internal audit was conducted to review the use of a newly implemented IGRA at the Hôpital du Sacré-Coeur de Montréal (Montréal, Québec to evaluate its concordance with Canadian recommendations and its implication on diagnosis.

  6. 利用 Beta 函数和 Gamma 函数推导组合恒等式%Derived Combinatorial Identities from Beta Function and Gamma Function

    Institute of Scientific and Technical Information of China (English)

    张秦; 刘玉堂

    2012-01-01

      Based on the theorem 1, series of combinatorial identities are derived by using the properties and relationship of Beta function and Gamma function.%  以定理1为基础,用 Beta 函数和 Gamma 函数性质及其之间的关系,导出了一系列组合恒等式

  7. The organization of the gamma-delta-beta gene complex in normal and thalassemia cells.

    Science.gov (United States)

    Bank, A; Mears, J G; Ramirez, F; Burns, A L; Spence, S; Feldenzer, J; Baird, M

    1980-01-01

    Restriction enzyme digestion analysis and direct human globin gene cloning have permitted analysis of the physical arrangement of nucleotide sequences within and surrounding the human globin genes. With these methods it has been shown that the linear arrangement 5' to 3' of the globin genes is G gamma-A gamma-delta-beta. The G gamma and A gamma genes are separated by about 3.5 kilobases (kb), while the A gamma and delta genes are 15 kb apart, and the delta and beta 6.5 kb apart. Each of these genes contains a large intervening sequence (IVS) of approximately 1 kb in precisely the same position between condons 104 and 105. In addition, each of these genes has a small IVS between codons 30 and 31. In homozygous delta beta thalassemia DNA, there is deletion of all of the normal delta and beta gene fragments. However, a new fragment 4.2 kb in size containing the 5' end of the delta globin gene is retained. Retention of this fragment in delta beta thalassemia, but not in HPFH is consistent with a role for sequences in this region for limiting gamma globin gene expression. Studies to date suggest that the beta + and beta 0 thalassemias will be due to a heterogeneous group of DNA defects affecting either beta globin gene transcription or beta mRNA processing. In most cases of beta + and beta 0 thalassemia DNA analyzed, there is no detectable deletion of beta or delta genes. In three India beta 0 patients, deletion of the 3' end of the beta gene has been found. Analysis of cloned beta globin genes from a patient with beta + thalasseia shows differences from normal in the fragments generated by restriction enzymes which cut frequently. Whether these differences are responsible for the defect in thalassemia or are polymorphisms unrelated to thalassemia remains to be determined.

  8. Effect of gamma-irradiation on the whitening activity of {beta}-glucan

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Hun; Sung, Nak Yun; Jung, Pil Moon; Choi, Jong Il; Kim, Jin Kyu; Lee, Ju Woon [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Byun, Eui Hong [Chungnam Naitonal University, Daejeon (Korea, Republic of)

    2010-09-15

    This study evaluated the change in whitening activity of {beta}-glucan by gamma-irradiation. Tyrosinase inhibition was significantly increased in the samples with 30, 50, 10 kGy irradiated {beta}-glucan. Melanin synthesis of irradiated {beta}-glucan was measured from B16BL6 melanoma cell line treated with {alpha}-melanin stimulating hormone. Melanin synthesis was increased in the {alpha}-melanin stimulating hormone added group. However, it was decreased in the groups of 30, 50 and 100 kGy gamma-irradiated {beta}-glucan treated with {alpha}-melanin stimulating hormone. These results indicate that gamma irradiated {beta}-glucan may elevate the whitening activity. Therefore, gamma-irradiated {beta}-glucan could be used for nutraceutical foods in cosmetic industry.

  9. Detection of Interferon gamma using graphene and aptamer based FET-like electrochemical biosensor.

    Science.gov (United States)

    Farid, Sidra; Meshik, Xenia; Choi, Min; Mukherjee, Souvik; Lan, Yi; Parikh, Devanshi; Poduri, Shripriya; Baterdene, Undarmaa; Huang, Ching-En; Wang, Yung Yu; Burke, Peter; Dutta, Mitra; Stroscio, Michael A

    2015-09-15

    One of the primary goals in the scientific community is the specific detection of proteins for the medical diagnostics and biomedical applications. Interferon-gamma (IFN-γ) is associated with the tuberculosis susceptibility, which is one of the major health problems globally. We have therefore developed a DNA aptamer-based electrochemical biosensor that is used for the detection of IFN-γ with high selectivity and sensitivity. A graphene monolayer-based FET-like structure is incorporated on a PDMS substrate with the IFN-γ aptamer attached to graphene. Addition of target molecule induces a change in the charge distribution in the electrolyte, resulting in increase in electron transfer efficiency that was actively sensed by monitoring the change in current from the device. Change in current appears to be highly sensitive to the IFN-γ concentrations ranging from nanomolar (nM) to micromolar (μM) range. The detection limit of our IFN-γ electrochemical biosensor is found to be 83 pM. Immobilization of aptamer on graphene surface is verified using unique structural approach by Atomic Force Microscopy. Such simple and sensitive electrochemical biosensor has potential applications in infectious disease monitoring, immunology and cancer research in the future.

  10. Parameter estimation and use of gamma interferon assay for the diagnosis of bovine tuberculosis in Brazil

    Directory of Open Access Journals (Sweden)

    Luciano B. Lopes

    2012-04-01

    Full Text Available This study aimed to evaluate the interference of tuberculin test on the gamma-interferon (INFg assay, to estimate the sensitivity and specificity of the INFg assay in Brazilian conditions, and to simulate multiple testing using the comparative tuberculin test and the INFg assay. Three hundred-fifty cattle from two TB-free and two TB-infected herds were submitted to the comparative tuberculin test and the INFg assay. The comparative tuberculin test was performed using avian and bovine PPD. The INFg assay was performed by the BovigamTM kit (CSL Veterinary, Australia, according to the manufacturer's specifications. Sensitivity and specificity of the INFg assay were assessed by a Bayesian latent class model. These diagnostic parameters were also estimate for multiple testing. The results of INFg assay on D0 and D3 after the comparative tuberculin test were compared by the McNemar's test and kappa statistics. Results of mean optical density from INFg assay on both days were similar. Sensitivity and specificity of the INFg assay showed results varying (95% confidence intervals from 72 to 100% and 74 to 100% respectively. Sensitivity of parallel testing was over 97.5%, while specificity of serial testing was over 99.7%. The INFg assay proved to be a very useful diagnostic method.

  11. Gamma Interferon Production by Bovine γδ T Cells following Stimulation with Mycobacterial Mycolylarabinogalactan Peptidoglycan

    Science.gov (United States)

    Vesosky, B.; Turner, O. C.; Turner, J.; Orme, I. M.

    2004-01-01

    A large percentage of lymphocytes in the blood of cattle express the γδ T-cell receptor, but specific functions for these cells have not yet been clearly defined. There is evidence, however, that human, murine, and bovine γδ T cells have a role in the immune response to mycobacteria. This study investigated the ability of bovine γδ T cells to expand and produce gamma interferon (IFN-γ) in response to stimulation with mycobacterial products. Bovine γδ T cells, isolated from the peripheral blood of healthy cattle, expanded following in vitro stimulation with live mycobacteria, mycobacterial crude cell wall extract, and Mycobacterium bovis culture filtrate proteins. In addition, purified γδ T cells, cocultured with purified monocytes and interleukin-2, consistently produced significant amounts of IFN-γ in response to mycobacterial cell wall. The IFN-γ-inducing component of the cell wall was further identified as a proteolytically resistant, non-sodium dodecyl sulfate-soluble component of the mycolylarabinogalactan peptidoglycan. PMID:15271921

  12. Retinyl Palmitate Supplementation Modulates T-bet and Interferon Gamma Gene Expression in Multiple Sclerosis Patients.

    Science.gov (United States)

    Mohammadzadeh Honarvar, Niyaz; Harirchian, Mohammad Hossein; Abdolahi, Mina; Abedi, Elahe; Bitarafan, Sama; Koohdani, Fariba; Siassi, Feridoun; Sahraian, Mohammad Ali; Chahardoli, Reza; Zareei, Mahnaz; Salehi, Eisa; Geranmehr, Maziyar; Saboor-Yaraghi, Ali Akbar

    2016-07-01

    Vitamin A derivatives such as retinoic acid may improve the impaired balance of CD4+ T cells in autoimmune and inflammatory diseases. This study is a double-blind randomized trial to evaluate the effect of vitamin A (as form of retinyl palmitate) supplementation on multiple sclerosis (MS) patients. Thirty-nine patients were enrolled and randomly assigned to two groups. Both groups were followed for 6 months. The experimental group received 25,000 IU of retinyl palmitate daily, while the control group received a placebo. Before and after the study, the expression of interferon gamma (IFN-γ) and T-bet genes was evaluated in peripheral blood mononuclear cells of patients by RT-PCR. The results showed that after 6 months of supplementation, expression of IFN-γ and T-bet was significantly decreased. These data suggest that retinyl palmitate supplementation can modulate the impaired balance of Th1 and Th2 cells and vitamin A products that may be involved in the therapeutic mechanism of vitamin A in MS patients. This study provides information regarding the decreased gene expression of IFN-γ and T-bet in MS by retinyl palmitate supplementation. PMID:27122150

  13. Personnel monitoring and dosimetry (beta and gamma) - external

    International Nuclear Information System (INIS)

    Personnel monitoring is the periodic measurement (monthly or quarterly service) of radiation doses received by radiation workers. The monitoring/service period for a given institution is mainly decided by the potential of receiving doses/exposures by occupational radiation workers. Ionizing radiations viz. neutrons, photons (X-rays and gamma) and beta particles are commonly encountered by radiation workers and contribute towards radiation doses. The main aim of personnel monitoring is to ensure that the dose limits as stipulated by the regulatory authorities are followed. It may also help in the segregation of various personnel as per dose received in case of emergency/radiation accidents. In addition, external monitoring provides information on the external radiation exposure of individuals working with radioactive materials and/or radiation producing devices and assist in work planning, allow control of doses at the workplace

  14. Inactivation of human gamma interferon by Pseudomonas aeruginosa proteases: elastase augments the effects of alkaline protease despite the presence of alpha 2-macroglobulin.

    OpenAIRE

    Horvat, R T; Clabaugh, M.; Duval-Jobe, C.; Parmely, M J

    1989-01-01

    Pseudomonas aeruginosa alkaline protease (AP) has recently been shown to produce limited proteolysis of human gamma interferon (IFN-gamma) and thereby destroy the antiviral and macrophage-activating activities of the lymphokine. In the present study we describe some of the characteristics of Pseudomonas elastase (E) with regard to inactivation of human IFN-gamma. The inhibitory effect of E on IFN-gamma bioactivity differed from that of AP in that the direct effects of E were reduced in the pr...

  15. Measuring and evaluating interferon beta-induced antibodies in patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Ross, C; Clemmesen, K M; Sørensen, P S;

    2006-01-01

    Administration of interferons (IFNs) may induce antibodies that interfere with therapeutic efficacy. We have optimized and validated methods for large-scale economic screening. Sera from patients with relapsing-remitting multiple sclerosis (MS) were investigated for binding antibody (BAb) by prot......Administration of interferons (IFNs) may induce antibodies that interfere with therapeutic efficacy. We have optimized and validated methods for large-scale economic screening. Sera from patients with relapsing-remitting multiple sclerosis (MS) were investigated for binding antibody (BAb...

  16. Human gamma interferon and tumor necrosis factor exert a synergistic blockade on the replication of herpes simplex virus.

    Science.gov (United States)

    Feduchi, E; Alonso, M A; Carrasco, L

    1989-03-01

    The replication of herpes simplex virus type 1 (HSV-1) is not inhibited in either HeLa or HEp-2 cells treated with human alpha interferon (HuIFN-alpha), particularly when high multiplicities of infection are used. However, HuIFN-gamma partially inhibits HSV-1 translation in HEp-2 cells infected at low multiplicities. Under these conditions, the transcription of genes alpha 22, TK, and gamma 0 is greatly diminished. The combined addition of human tumor necrosis factor (TNF) and HuIFN-gamma to HEp-2 cells exerts a synergistic inhibition of HSV-1 translation. Cells treated with both cytokines continue synthesizing cellular proteins, even 20 h after HSV-1 infection. As little as 10 U of IFN-gamma per ml blocked HSV-1 DNA replication, provided that TNF was also present in the medium. Analyses of HSV-1 gene transcription suggest that the action of both TNF and IFN-gamma blocked a step that comes at or prior to early HSV-1 gene expression. This early step in HSV-1 replication inhibited by TNF and IFN-gamma occurs after virus attachment and entry into cells, since the internalization of radioactive HSV-1 virion particles was not blocked by the presence of the two cytokines. Therefore, we conclude that the synergistic action of TNF plus IFN-gamma affects a step in HSV-1 replication that comes after virus entry but before or at the transcription of immediate-early genes.

  17. Impaired virus control and severe CD8+ T-cell-mediated immunopathology in chimeric mice deficient in gamma interferon receptor expression on both parenchymal and hematopoietic cells

    DEFF Research Database (Denmark)

    Henrichsen, Pernille; Bartholdy, Christina; Christensen, Jan Pravsgaard;

    2005-01-01

    Bone marrow chimeras were used to determine the cellular target(s) for the antiviral activity of gamma interferon (IFN-gamma). By transfusing such mice with high numbers of naive virus-specific CD8(+) T cells, a system was created in which the majority of virus-specific CD8(+) T cells would be...

  18. 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...

  19. Observation of Doppler broadening in $\\beta$-delayed proton-$\\gamma$ decay

    CERN Document Server

    Schwartz, S B; Bennett, M B; Liddick, S N; Perez-Loureiro, D; Bowe, A; Chen, A A; Chipps, K A; Cooper, N; Irvine, D; McNeice, E; Montes, F; Naqvi, F; Ortez, R; Pain, S D; Pereira, J; Prokop, C; Quaglia, J; Quinn, S J; Sakstrup, J; Santia, M; Shanab, S; Simon, A; Spyrou, A; Thiagalingam, E

    2015-01-01

    Background: The Doppler broadening of $\\gamma$-ray peaks due to nuclear recoil from $\\beta$-delayed nucleon emission can be used to measure the energies of the nucleons. This method has never been tested using $\\beta$-delayed proton emission or applied to a recoil heavier than $A=10$. Purpose: To test and apply this Doppler broadening method using $\\gamma$-ray peaks from the $^{26}$P($\\beta p\\gamma$)$^{25}$Al decay sequence. Methods: A fast beam of $^{26}$P was implanted into a planar Ge detector, which was used as a $^{26}$P $\\beta$-decay trigger. The SeGA array of high-purity Ge detectors was used to detect $\\gamma$ rays from the $^{26}$P($\\beta p\\gamma$)$^{25}$Al decay sequence. Results: Radiative Doppler broadening in $\\beta$-delayed proton-$\\gamma$ decay was observed for the first time. The Doppler broadening analysis method was verified using the 1613 keV $\\gamma$-ray line for which the proton energies were previously known. The 1776 keV $\\gamma$ ray de-exciting the 2720 keV $^{25}$Al level was observed...

  20. The effective exponent gamma(Q) and the slope of the beta function

    CERN Document Server

    Stevenson, P M

    2016-01-01

    The slope of the beta function at a fixed point is commonly thought to be RG invariant and to be the critical exponent gamma* that governs the approach of any physical quantity R to its fixed-point limit: R*-R proportional to Q^gamma*. Chyla has shown that this is not quite true. Here we define a proper RG invariant, the "effective exponent" gamma(Q), whose fixed-point limit is the true gamma*.

  1. Methylation status of the interferon-gamma gene promoter in chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective To evaluate the methylation status at CpG site -55 in the interferon-gamma (IFN-7) gene promoter and its effect on IFN-7 expression in chronic hepatitis B. Method The authors recruited 30 patients with UBeAg-positive chronic hepatitis B (CHB), 30 HBeAg-negative CHB patients, and 30 healthy blood donors. Pyrosequeneing was used to determine the methylation status at CpG site -55 in the IFN-γ gene promoter following bisulfite treatment of DNA in peripheral blood mononuclear cells (PBMCs). The expression of IFN-γ was analyzed by real-time RT-PCR and ELISA. HBV DNA in PBMCs was detected by nested PCR. Results The methylation level at CpG site -55 in the IFN-γ gene promoter was significantly increased, resulting in subsequent down-regulation of the expression of this cytoldne in CHB. The methylation level at CpG site -55 was significantly higher in HBeAg-positive patients than in HBeAg-negative ones (P<0.01) and was also significantly higher in PBMCs from HBV DNA-positive patients than from HBV DNA-negative ones (P<0.01) ; the methylation level at CpG site -55 was positively correlated with the amount of HBV DNA in serum (P<0.01). Oonclusion IFN-γ gene expression appears to be regulated by methylation of the IFN-γ gene promoter in CHB; the methylation level at CpG site -55 is associated with HBV infection.

  2. Comparing interferon-gamma release assays to tuberculin skin test in Thai children with tuberculosis exposure.

    Directory of Open Access Journals (Sweden)

    Hong-Van Tieu

    Full Text Available Data on the performance of interferon-gamma release assays (IGRAs, QuantiFERON TB Gold In-tube (QFNGIT and T-Spot.TB, in diagnosing tuberculosis (TB are limited in Southeast Asia. This study aims to compare the performances of the two IGRAs and TST in Thai children with recent TB exposure.This multicenter, prospective study enrolled children with recent exposure to active TB adults. Children were investigated for active TB. TST was performed and blood collected for T-Spot.TB and QFNGIT.158 children were enrolled (87% TB-exposed and 13% active TB, mean age 7.2 years. Only 3 children had HIV infection. 66.7% had TST≥10 mm, while 38.6% had TST≥15 mm. 32.5% had positive QFNGIT; 29.9% had positive T-Spot.TB. QFNGIT and T-Spot.TB positivity was higher among children with active TB compared with TB-exposed children. No indeterminate IGRA results were detected. No statistically significant differences between the performances of the IGRAs and TST at the two cut-offs with increasing TB exposure were detected. Concordance for positive IGRAs and TST ranged from 42-46% for TST≥10 mm and 62-67% for TST≥15 mm. On multivariable analyses, exposure to household primary/secondary caregiver with TB was associated with positive QFNGIT. Higher TB contact score and active TB were associated with positive T-Spot.TB.Both QFNGIT and T-Spot.TB performed well in our Thai pediatric study population. No differences in the performances between tests with increasing TB exposure were found. Due to accessibility and low cost, using TST may more ideal than IGRAs in diagnosing latent and active TB in healthy children in Thailand and other similar settings.

  3. Interferon gamma Profile in Egyptian Infants with Respiratory Syncytial Virus bronchiolitis

    Directory of Open Access Journals (Sweden)

    Maha E. Omran1, Mohamed AE. Fahmy2, Manal M. Zaher3

    2008-03-01

    Full Text Available Viral bronchiolitis is one of the leading causes for hospitalization of infants in the world and causes an estimated one million deaths per year worldwide. Respiratory syncytial virus (RSV is associated with the majority of cases. During the last few years it has become increasingly clear that T cells contribute to the abnormal regulation of the immune response in viral diseases since these cells are potent producers of a large variety of cytokines. It was reported that cord blood interferon gamma (IFN- responses were inversely related to the frequency of viral respiratory infections. To ascertain whether RSV infection promotes a different IFN- profile to that induced by other respiratory infections, thirty-two infants with severe bronchiolitis were enrolled in this study. RSV-IgM was detected by immunofluorescent technique in 23/32 patients. Serum IFN- levels in RSV+ infants were significantly lower than RSV- (p < 0.001. In vitro stimulation of peripheral blood cells followed by flow cytometery combined with intracellular cytokine staining revealed that both CD4+ and CD8+ cells contribute in IFN- production. The percentage of CD4+ cells producing IFN- in RSV+ was significantly lower (P < 0.05 than those in RSV-, while the difference in % of CD8+ between RSV+ and RSV- was non significant. Our conclusions are that RSV infection is associated with severe decreased IFN- responses. Both CD4+ and CD8+ cells contribute in IFN- production during RSV bronchiolitis. RSV infection promotes a different IFN- profile from that induced by other respiratory infections.

  4. Challenges in the development of an immunochromatographic interferon-gamma test for diagnosis of pleural tuberculosis.

    Directory of Open Access Journals (Sweden)

    Claudia M Denkinger

    Full Text Available Existing diagnostic tests for pleural tuberculosis (TB have inadequate accuracy and/or turnaround time. Interferon-gamma (IFNg has been identified in many studies as a biomarker for pleural TB. Our objective was to develop a lateral flow, immunochromatographic test (ICT based on this biomarker and to evaluate the test in a clinical cohort. Because IFNg is commonly present in non-TB pleural effusions in low amounts, a diagnostic IFNg-threshold was first defined with an enzyme-linked immunosorbent assay (ELISA for IFNg in samples from 38 patients with a confirmed clinical diagnosis (cut-off of 300 pg/ml; 94% sensitivity and 93% specificity. The ICT was then designed; however, its achievable limit of detection (5000 pg/ml was over 10-fold higher than that of the ELISA. After several iterations in development, the prototype ICT assay for IFNg had a sensitivity of 69% (95% confidence interval (CI: 50-83 and a specificity of 94% (95% CI: 81-99% compared to ELISA on frozen samples. Evaluation of the prototype in a prospective clinical cohort (72 patients on fresh pleural fluid samples, in comparison to a composite reference standard (including histopathological and microbiologic test results, showed that the prototype had 65% sensitivity (95% CI: 44-83 and 89% specificity (95% CI: 74-97. Discordant results were observed in 15% of samples if testing was repeated after one freezing and thawing step. Inter-rater variability was limited (3%; 1 out of 32. In conclusion, despite an iterative development and optimization process, the performance of the IFNg ICT remained lower than what could be expected from the published literature on IFNg as a biomarker in pleural fluid. Further improvements in the limit of detection of an ICT for IFNg, and possibly combination of IFNg with other biomarkers such as adenosine deaminase, are necessary for such a test to be of value in the evaluation of pleural tuberculosis.

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

    Directory of Open Access Journals (Sweden)

    Ding Wang

    Full Text Available OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Our results suggest that functional IFN-γ SNPs and their haplotypes are associated with pneumonia-induced sepsis.

  6. 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. PMID:26303093

  7. In vivo evidence for interferon-gamma-mediated homeostatic mechanisms in small intestine of the NHE3 Na+/H+ exchanger knockout model of congenital diarrhea.

    Science.gov (United States)

    Woo, Alison L; Gildea, Lucy A; Tack, Leslie M; Miller, Marian L; Spicer, Zachary; Millhorn, David E; Finkelman, Fred D; Hassett, Daniel J; Shull, Gary E

    2002-12-13

    Mice lacking NHE3, the major absorptive Na(+)/H(+) exchanger in the intestine, are the only animal model of congenital diarrhea. To identify molecular changes underlying compensatory mechanisms activated in chronic diarrheas, cDNA microarrays and Northern blot analyses were used to compare global mRNA expression patterns in small intestine of NHE3-deficient and wild-type mice. Among the genes identified were members of the RegIII family of growth factors, which may contribute to the increased absorptive area, and a large number of interferon-gamma-responsive genes. The latter finding is of particular interest, since interferon-gamma has been shown to regulate ion transporter activities in intestinal epithelial cells. Serum interferon-gamma was elevated 5-fold in NHE3-deficient mice; however, there was no evidence of inflammation, and unlike conditions such as inflammatory bowel disease, levels of other cytokines were unchanged. In addition, quantitative PCR analysis showed that up-regulation of interferon-gamma mRNA was localized to the small intestine and did not occur in the colon, spleen, or kidney. These in vivo data suggest that elevated interferon-gamma, produced by gut-associated lymphoid tissue in the small intestine, is part of a homeostatic mechanism that is activated in response to the intestinal absorptive defect in order to regulate the fluidity of the intestinal tract. PMID:12370192

  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. 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.

  10. Beowulf - Beta-Gamma Detector Calibration Graphical User Interface

    Energy Technology Data Exchange (ETDEWEB)

    McIntyre, Justin I.; Schrom, Brian T.; Cooper, Matthew W.; Haas, Derek A.; Hayes, James C.

    2009-09-21

    Pacific Northwest National Laboratory (PNNL) has demonstrated significant advancement in using beta-gamma coincidence detectors to detect a wide range of radioxenon isotopes. To obtain accurate activities with the detector it must be properly calibrated by measuring a series of calibration gas samples. The data is analyzed to create the calibration block used in the International Monitoring System file format. Doing the calibration manually has proven to be tedious and prone to errors, requiring a high degree of expertise. The Beowulf graphical user interface (GUI) is a software application that encompasses several components of the calibration task and generates a calibration block, as well as, a detailed report describing the specific calibration process used. This additional document can be used as a Quality assurance certificate to assist in auditing the calibration. This paper consists of two sections. Section 1 will describe the capabilities of Beowulf and section 2 will be a representative report generated or the 137Cs calibration and quality assurance source.

  11. Preserved in vivo response to interferon-alpha in multiple sclerosis patients with neutralising antibodies against interferon-beta (REPAIR study)

    DEFF Research Database (Denmark)

    Magyari, Melinda; Bach Søndergaard, Helle; Sellebjerg, Finn;

    2013-01-01

    BACKGROUND: A major problem in the treatment of multiple sclerosis (MS) patients with interferon-beta (IFN-β) is the development of neutralising antibodies (NAbs). High levels of NAbs block the induction of IFN-β-inducible markers, including Myxovirus Resistance Protein A (encoded by the MX1 gene...... an injection of IFN-α compared with the response after an injection of IFN-β. RESULTS: In all 10 patients we found high MX1 expression after injection of IFN-α 6 MIU, indicating a preserved in vivo response to IFN-α. We measured the gene expression index of immune system genes in blood cells from the 10 NAb......-positive patients after IFN-α treatment and 10 NAb-negative patients after injection of IFN-β. We found a significantly increased expression of a number of genes, including MX1, IFI27, IL10 and TNFSF10 (encoding TRAIL) in the NAb-positive patients treated with IFN-α. INTERPRETATION: IFN-α could be a therapeutic...

  12. 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...... indicated that tyrosine residues in GH receptor are not necessary for tyrosyl phosphorylation of IRS-2; however, the regions of GH receptor necessary for IRS-2 tyrosyl phosphorylation are the same as those required for JAK2 association and tyrosyl phosphorylation. The role of IRS-2 as a signaling molecule...... of multiple members of the cytokine family of receptors that activate JAK kinases....

  13. Beta-gamma system, pure spinors and Hilbert series of arc spaces

    OpenAIRE

    Bhamidipati, Chandrasekhar; Ray, Koushik

    2014-01-01

    Algorithms are presented for calculating the partition function of constrained beta-gamma systems in terms of the generating functions of the individual fields of the theory, the latter obtained as the Hilbert series of the arc space of the algebraic variety defined by the constraint. Examples of a beta-gamma system on a complex surface with an $A_1$ singularity and pure spinors are worked out and compared with existing results.

  14. The assay of encapsulated beta-gamma emitting waste: feasibility study

    International Nuclear Information System (INIS)

    This report contains a discussion of the techniques and instrumentation available for the determination of Beta-Gamma emitting radionuclides in encapsulated radioactive waste. Where applicable, consideration has been given to the practical difficulties associated with the assay of certain waste forms. The levels of detection have been estimated but further work is required in this and other areas. A suggestion is made for incorporating the beta-gamma assay in the same facility as an alpha assay. (author)

  15. The clinical effect of neutralizing antibodies against interferon-beta is independent of the type of interferon-beta used for patients with relapsing-remitting multiple sclerosis

    DEFF Research Database (Denmark)

    Koch-Henriksen, N.; Sorensen, P.S.; Bendtzen, K.;

    2009-01-01

    considered as NAb-positive. We used a mixed logistic regression analysis in which NAb-status (three levels), IFN beta-preparation, and time since treatment started were included as explanatory variables, and relapse rate as response variable. RESULTS: In 1,309 patients, who were observed for 21,958 months......, 32.3% were classified as NAb-positive. The odds-ratio (OR) for relapses in NAb-positive months compared with NAb-negative months was 1.25; P = 0.02. The risk of relapses was higher with Betaferon than with Rebif22 (OR 1.26; P < 0.01). The effect of NAb-level on relapses was independent of whether the...

  16. Peroxisomal beta-oxidation activities and gamma-decalactone production by the yeast Yarrowia lipolytica.

    Science.gov (United States)

    Pagot, Y; Le Clainche, A; Nicaud, J M; Wache, Y; Belin, J M

    1998-03-01

    gamma-Decalactone is a peachy aroma compound resulting from the peroxisomal beta-oxidation of ricinoleic acid by yeasts. The expression levels of acyl-CoA oxidase (gene deletion) and 3-ketoacyl-CoA thiolase activities (gene amplification on replicative plasmids) were modified in the yeast Yarrowia lipolytica. The effects of these modifications on beta-oxidation were measured. Overexpression of thiolase activity did not have any effect on the overall beta-oxidation activity. The disruption of one of the acyl-CoA oxidase genes resulted in an enhanced activity. The enhancement led to an increase of overall beta-oxidation activity but reduced the gamma-decalactone production rates. This seemed to indicate a non-rate-limiting role for beta-oxidation in the biotransformation of ricinoleic acid to gamma-decalactone by the yeast Yarrowia lipolytica. All strains produced and then consumed gamma-decalactone. We checked the ability of the different strains to consume gamma-decalactone in a medium containing the lactone as sole carbon source. The consumption of the strain overexpressing acyl-CoA oxidase activity was higher than that of the wild-type strain. We concluded that peroxisomal beta-oxidation is certainly involved in gamma-decalactone catabolism by the yeast Y. lipolytica. The observed production rates probably depend on an equilibrium between production and consumption of the lactone. PMID:9581293

  17. Interleukin-2 protects neonatal mice from lethal herpes simplex virus infection: a macrophage-mediated, gamma interferon-induced mechanism.

    Science.gov (United States)

    Kohl, S; Loo, L S; Drath, D B; Cox, P

    1989-02-01

    Administration of human recombinant interleukin-2 (IL-2) protected neonatal mice from a lethal herpes simplex virus (HSV) infection. Protection was not associated with viral antibody production, enhanced natural killer cell cytotoxicity, or intrinsic resistance of macrophages to viral infection. Protection was associated with increased macrophage-mediated antiviral antibody-dependent cellular cytotoxicity (ADCC). Spleen cells from IL-2-treated neonatal mice and from neonatal mice that were treated in vitro with IL-2 transferred protection to neonatal mice. These cells, by adherence, silica, and asialo GM 1 antibody treatment, were shown to be macrophages. IL-2 treatment in vitro enhanced the neonatal macrophages' ADCC function and superoxide release. Similar protection was induced by gamma interferon (IFN-gamma)-treated spleen cells. Antibody to IFN-gamma ablated both IFN-gamma- and IL-2-induced protection by adherent spleen cells. Thus, IL-2-mediated protection against murine neonatal HSV infection was affected by stimulated macrophage activity, via helper T cell-produced IFN-gamma. PMID:2492588

  18. Characterization of the interaction between recombinant human interferon-gamma and its receptor on human polymorphonuclear leukocytes

    International Nuclear Information System (INIS)

    The interaction of human recombinant interferon-gamma (rIFN-gamma) with human polymorphonuclear cells (PMN) was investigated. Bolton-Hunter radioiodinated rIFN-gamma bound to PMN in a specific and saturable manner. Eleven hundred binding sites were observed with a Ka of 0.56 x 10(10) M-1. Binding to PMN was rapid with a K1 of 9 x 10(5) M-1 sec-1 at 4 degree C. At 37 degree C binding was complete within 6 min. About 50% of bound ligand was internalized within 30 min at 37 degree C. The receptor demonstrated moderate lability at 37 degree C in culture. After 1 h at 37 degree C, PMN lost 80% of their 125I-rIFN-gamma binding sites. This loss was reversed in part by the presence of interleukin-1 in the culture, but not tumor necrosis factor. These studies provide a framework for further investigation into the signalling process of rIFN-gamma on PMN

  19. Salivary Interferon Gamma and Interleukin-4 Levels in Patients Suffering from Oral Lichen Planus

    Directory of Open Access Journals (Sweden)

    Hossein Malekzadeh

    2015-10-01

    Full Text Available Objective: Oral lichen planus (OLP is a chronic inflammatory disease. Immunological factor may act as etiological factor. The cellular immune cells such as T cells are important in pathogenesis. Interferon gamma (IFN-γ and interleukin 4 (IL-4 are secreted by T-helper 1 (Th1 and Th2, respectively. The aim of this study was to investigate the correlation between salivary levels of IFN-γ and IL-4 with OLP. Materials and Methods: This case control study included sixty three Iranian OLP patients who were selected from the Department of Oral Medicine of Ahvaz Jundishapur University of Medical Sciences from January to July 2013. An equal number of healthy volunteers were also selected as a control group. The OLP patients were then divided into two following sub-groups: reticular (n=30 and erythematous/ulcerative (n=33. All patients had no systemic disease and received no medication. IFN-γ and IL-4 levels in whole unstimulated saliva (WUS were measured using the enzyme-linked immunosorbent assay (ELISA test. Data analysis was done using t test, ANOVA, least significant difference (LSD test, and the Kruskal-Wallis test. Results: Reticular OLP patients showed higher salivary IFN-γ (7.74 ± 0.09 pg/ml and IL-4 (3.876 ± 0.05 pg/ml levels compared with the control group, indicating that difference was significant. Salivary IFN-γ/IL-4 ratio significantly increased compared with control group (P=0.042. Salivary IFN-γ and IL-4 levels between sub-groups (reticular and erythematous/ulcerative were not significantly different (2.6 ± 0.06 and 2.3 ± 0.05, respectively, P<0.05. Conclusion: Salivary IFN-γ and IL-4 levels were increased in OLP patients. An increase of salivary IFN-γ/IL-4 ratio in OLP patients showed that Th1 might have a dominant role in the OLP pathogenesis.

  20. Mechanism underlying defective interferon gamma-induced IDO expression in non-obese diabetic mouse fibroblasts.

    Directory of Open Access Journals (Sweden)

    Azadeh Hosseini-Tabatabaei

    Full Text Available Indoleamine 2,3-dioxygenase (IDO can locally suppress T cell-mediated immune responses. It has been shown that defective self-tolerance in early prediabetic female non-obese diabetic (NOD mice can be attributed to the impaired interferon-gamma (IFN-γ- induced IDO expression in dendritic cells of these animals. As IFN-γ can induce IDO in both dendritic cells and fibroblasts, we asked the question of whether there exists a similar defect in IFN-γ-induced IDO expression in NOD mice dermal fibroblasts. To this end, we examined the effect of IFN-γ on expression of IDO and its enzymatic activity in NOD dermal fibroblasts. The results showed that fibroblasts from either prediabetic (8 wks of age female or male, and diabetic female or male (12 and 24 wks of age respectively NOD mice failed to express IDO in response to IFN-γ treatment. To find underlying mechanisms, we scrutinized the IFN- γ signaling pathway and investigated expression of other IFN-γ-modulated factors including major histocompatibility complex class I (MHC-I and type I collagen (COL-I. The findings revealed a defect of signal transducer and activator of transcription 1 (STAT1 phosphorylation in NOD cells relative to that of controls. Furthermore, we found an increase in MHC-I and suppression of COL-I expression in fibroblasts from both NOD and control mice following IFN-γ treatment; indicating that the impaired response to IFN-γ in NOD fibroblasts is specific to IDO gene. Finally, we showed that an IFN-γ-independent IDO expression pathway i.e. lipopolysaccharide (LPS-mediated-c-Jun kinase is operative in NOD mice fibroblast. In conclusion, the findings of this study for the first time indicate that IFN-γ fails to induce IDO expression in NOD dermal fibroblasts; this may partially be due to defective STAT1 phosphorylation in IFN-γ-induced-IDO signaling pathway.

  1. Secretion of biologically active interferon-gamma inducible protein-10 (IP-10 by Lactococcus lactis

    Directory of Open Access Journals (Sweden)

    Saucedo-Cardenas Odila

    2008-07-01

    Full Text Available Abstract Background Chemokines are a large group of chemotactic cytokines that regulate and direct migration of leukocytes, activate inflammatory responses, and are involved in many other functions including regulation of tumor development. Interferon-gamma inducible-protein-10 (IP-10 is a member of the C-X-C subfamily of the chemokine family of cytokines. IP-10 specifically chemoattracts activated T lymphocytes, monocytes, and NK cells. IP-10 has been described also as a modulator of other antitumor cytokines. These properties make IP-10 a novel therapeutic molecule for the treatment of chronic and infectious diseases. Currently there are no suitable live biological systems to produce and secrete IP-10. Lactococcus lactis has been well-characterized over the years as a safe microorganism to produce heterologous proteins and to be used as a safe, live vaccine to deliver antigens and cytokines of interest. Here we report a recombinant strain of L. lactis genetically modified to produce and secrete biologically active IP-10. Results The IP-10 coding region was isolated from human cDNA and cloned into an L. lactis expression plasmid under the regulation of the pNis promoter. By fusion to the usp45 secretion signal, IP-10 was addressed out of the cell. Western blot analysis demonstrated that recombinant strains of L. lactis secrete IP-10 into the culture medium. Neither degradation nor incomplete forms of IP-10 were detected in the cell or supernatant fractions of L. lactis. In addition, we demonstrated that the NICE (nisin-controlled gene expression system was able to express IP-10 "de novo" even two hours after nisin removal. This human IP-10 protein secreted by L. lactis was biological active as demonstrated by Chemotaxis assay over human CD3+T lymphocytes. Conclusion Expression and secretion of mature IP-10 was efficiently achieved by L. lactis forming an effective system to produce IP-10. This recombinant IP-10 is biologically active as

  2. The elephant interferon gamma assay: a contribution to diagnosis of tuberculosis in elephants.

    Science.gov (United States)

    Angkawanish, T; Morar, D; van Kooten, P; Bontekoning, I; Schreuder, J; Maas, M; Wajjwalku, W; Sirimalaisuwan, A; Michel, A; Tijhaar, E; Rutten, V

    2013-11-01

    Mycobacterium tuberculosis (M. tb) has been shown to be the main causative agent of tuberculosis in elephants worldwide. M. tb may be transmitted from infected humans to other species including elephants and vice versa, in case of prolonged intensive contact. An accurate diagnostic approach covering all phases of the infection in elephants is required. As M. tb is an intracellular pathogen and cell-mediated immune (CMI) responses are elicited early after infection, the skin test is the CMI assay of choice in humans and cattle. However, this test is not applicable in elephants. The interferon gamma (IFN-γ) assay is considered a good alternative for the skin test in general, validated for use in cattle and humans. This study was aimed at development of an IFN-γ assay applicable for diagnosis of tuberculosis in elephants. Recombinant elephant IFN-γ (rEpIFN-γ) produced in eukaryotic cells was used to immunize mice and generate the monoclonal antibodies. Hybridomas were screened for IFN-γ-specific monoclonal antibody production and subcloned, and antibodies were isotyped and affinity purified. Western blot confirmed recognition of the rEpIFN-γ. The optimal combination of capture and detection antibodies selected was able to detect rEpIFN-γ in concentrations as low as 1 pg/ml. The assay was shown to be able to detect the native elephant IFN-γ, elicited in positive-control cultures (pokeweed mitogen (PWM), phorbol myristate acetate plus ionomycin (PMA/I)) of both Asian and African elephant whole-blood cultures (WBC). Preliminary data were generated using WBC from non-infected elephants, a M. tb infection-suspected elephant and a culture-confirmed M. tb-infected elephant. The latter showed measurable production of IFN-γ after stimulation with ESAT6/CFP10 PPDB and PPDA in concentration ranges as elicited in WBC by Mycobacterium tuberculosis complex (MTBC)-specific antigens in other species. Hence, the IFN-γ assay presented potential as a diagnostic tool for the

  3. Interferon Gamma, but not Calcitriol Improves the Osteopetrotic Phenotypes in ADO2 Mice.

    Science.gov (United States)

    Alam, Imranul; Gray, Amie K; Acton, Dena; Gerard-O'Riley, Rita L; Reilly, Austin M; Econs, Michael J

    2015-11-01

    ADO2 is a heritable osteosclerotic disorder that usually results from heterozygous missense dominant negative mutations in the chloride channel 7 gene (CLCN7). ADO2 is characterized by a wide range of features and severity, including multiple fractures, impaired vision due to secondary bony overgrowth and/or the lack of the optical canal enlargement with growth, and osteonecrosis/osteomyelitis. The disease is presently incurable, although anecdotal evidence suggests that calcitriol and interferon gamma-1b (IFN-G) may have some beneficial effects. To identify the role of these drugs for the treatment of ADO2, we utilized a knock-in (G213R mutation in Clcn7) ADO2 mouse model that resembles the human disease. Six-week-old ADO2 heterozygous mice were administered vehicle (PBS) or calcitriol or IFN-G 5 times per week for 8 weeks. We determined bone phenotypes using DXA and μCT, and analyzed serum biochemistry and bone resorption markers. ADO2 mice treated with all doses of IFN-G significantly (pTV gain in both male and female compared to the vehicle group. In contrast, mice treated with low and medium doses of calcitriol showed a trend of higher aBMD and BV/TV whereas high dose calcitriol significantly (p<0.05) increased bone mass compared to the vehicle group. The calcium and phosphorus levels did not differ between vehicle and IFN-G or calcitriol treated mice; however, we detected significantly (p<0.05) elevated levels of CTX/TRAP5b ratio in IFN-G treated mice. Our findings indicate that while IFN-G at all doses substantially improved the osteopetrotic phenotypes in ADO2 heterozygous mice, calcitriol treatment at any dose did not improve the phenotype and at high dose further increased bone mass. Thus, use of high dose calcitriol therapy in ADO2 patients merits serious reconsideration. Importantly, our data support the prospect of a clinical trial of IFN-G in ADO2 patients. PMID:25943708

  4. 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

    as these influence central nervous system (CNS) transmigration and inflammation. At 'steady state' (>/=1 day after the most recent IFN-beta injection), IFN-beta treatment increased CD4(+) T-cell surface expression of CC chemokine receptor (CCR)4, CCR5 and CCR7 after 3 months of treatment, whereas that of CXC...... and immunoregulatory genes. In conclusion, IFN-beta treatment caused 'steady-state' increases of several chemokine receptors relevant for CD4(+) T-lymphocyte trafficking and function, possibly facilitating lymphocyte migration into the CNS. An important therapeutic effect of IFN-beta treatment may be the normalization...... of a decreased Th2-related CD4(+) T-cell CCR4 expression in MS patients. Surface chemokine receptor expression and CXCL10 varied according to the timing of blood sampling in relation to the most recent IFN-beta injection. Thus, it is imperative to distinguish acute effects of IFN-beta from steady-state effects....

  5. Adverse events of interferon beta-1a: a prospective multi-centre international ICH-GCP-based CRO-supported external validation study in daily practice.

    NARCIS (Netherlands)

    Jongen, P.J.H.; Sindic, C.; Sanders, E.; Hawkins, S.; Linssen, W.; Munster, E. van; Frequin, S.T.F.M.; Borm, G.F.

    2011-01-01

    BACKGROUND: Due to methodological shortcomings the available post-registration data on the adverse events (AEs) occurring in interferon beta-1a (INFb-1a)-treated patients fail to adequately validate phase III data and only partially inform on safety in daily practice. We assessed AEs in relapsing re

  6. 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...

  7. Potent systemic therapy of Multiple Myeloma utilizing Oncolytic Vesicular stomatitis virus coding for Interferon-beta

    OpenAIRE

    Naik, Shruthi; Nace, Rebecca; Barber, Glen N.; Russell, Stephen J.

    2012-01-01

    Multiple myeloma (MM) is an incurable malignancy of plasma secreting B-cells disseminated in the bone marrow. Successful utilization of oncolytic virotherapy for myeloma treatment requires a systemically administered virus that selectively destroys disseminated myeloma cells in an immune-competent host. Vesicular stomatitis virus (VSV) expressing Interferon-β (IFNβ) is a promising new oncolytic agent that exploits tumor-associated defects in innate immune signaling pathways to specifically de...

  8. Receptor Density Is Key to the Alpha2/Beta Interferon Differential Activities

    OpenAIRE

    Moraga, I.; Harari, D.; Schreiber, G.; Uze, G.; Pellegrini, S.

    2009-01-01

    Multiple type I interferons (IFN-α/β) elicit Jak/Stat activation, rapid gene induction, and pleiotropic effects, such as differentiation, antiviral protection, and blocks in proliferation, which are dependent on the IFN subtype and the cellular context. To date, ligand- and receptor-specific molecular determinants underlying IFN-α/β differential activities or potencies have been well characterized. To analyze cellular determinants that impact subtype-specific potency, human fibrosarcoma U5A-d...

  9. 75 FR 4877 - In the Matter of Beta Gamma Nuclear Radiology; Confirmatory Order Modifying License (Effective...

    Science.gov (United States)

    2010-01-29

    ... rule (72 FR 49139, August 28, 2007). The E-Filing process requires participants to submit and serve all... Gamma Nuclear Radiology; Confirmatory Order Modifying License (Effective Immediately) I Beta Gamma Nuclear Radiology (BGNR) (Licensee) is the holder of medical License No. 52-25542-01, issued by the...

  10. 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 y

  11. Improvement of impaired mitogen-induced interferon-gamma release of peripheral blood mononuclear cells derived from tumor patients by Factor AF2.

    Science.gov (United States)

    Baier, J E; Neumann, H A; Gallati, H; Ricken, D

    1991-01-01

    Factor AF2, a now standardized extract from liver and spleen of newborn lambs, showed myeloprotective capacity on platelet- and erythrocyte-count as well as on hemoglobinconcentration in patients undergoing aggressive chemotherapy. In addition, a possible influence on prolonged remission duration in patients with mammary carcinoma had been claimed. In this study, the effect of Factor AF2 on mitogen-induced interferon-gamma release by PBMC was tested in 23 healthy humans and in 23 tumor patients. All patients were prior to surgery and had not yet received radio- or chemotherapy at the time of examination. The interferon-gamma concentration of the supernatants was measured using an enzyme-linked immunosorbent assay (ELISA). The cells were stimulated with PHA at 7.5 micrograms/ml. In the reference group, interferon-gamma concentration rose to 26 units/ml and to 15.5 units/ml in the tumor patients. In the reference persons, an addition of Factor AF2 at concentrations from 10(1) micrograms/ml to 10(3) micrograms/ml resulted in a small non-significant decrease of interferon-gamma release. At 10(4) micrograms/ml, neither test group showed measurable interferon-gamma concentration. In the tumor patients, cocultivation with Factor AF2 until concentration of 10(2) micrograms/ml resulted in a dose-dependent increase of interferon-gamma release, where 20.5 units/ml interferon-gamma were reached. At 10(3) micrograms/ml, Factor AF2 showed no effect on interferon-gamma release compared with the stimulation with mitogen alone. Flow-cytometry analysis of CD3, CD4, CD8, CD16, CD19, CD56, and HLA-DR expression of the PBMC deriving either from reference persons or from patients revealed an almost identical distribution. A slight difference in CD16-positive and HLA-DR positive cells, respectively, was not significant. PMID:1788474

  12. Analysis of eight genes modulating interferon gamma and human genetic susceptibility to tuberculosis: a case-control association study

    Directory of Open Access Journals (Sweden)

    Hoal Eileen G

    2010-06-01

    Full Text Available Abstract Background Interferon gamma is a major macrophage-activating cytokine during infection with Mycobacterium tuberculosis, the causative pathogen of tuberculosis, and its role has been well established in animal models and in humans. This cytokine is produced by activated T helper 1 cells, which can best deal with intracellular pathogens such as M. tuberculosis. Based on the hypothesis that genes which regulate interferon gamma may influence tuberculosis susceptibility, we investigated polymorphisms in eight candidate genes. Methods Fifty-four polymorphisms in eight candidate genes were genotyped in over 800 tuberculosis cases and healthy controls in a population-based case-control association study in a South African population. Genotyping methods used included the SNPlex Genotyping System™, capillary electrophoresis of fluorescently labelled PCR products, TaqMan® SNP genotyping assays or the amplification mutation refraction system. Single polymorphisms as well as haplotypes of the variants were tested for association with TB using statistical analyses. Results A haplotype in interleukin 12B was nominally associated with tuberculosis (p = 0.02, but after permutation testing, done to assess the significance for the entire analysis, this was not globally significant. In addition a novel allele was found for the interleukin 12B D5S2941 microsatellite. Conclusions This study highlights the importance of using larger sample sizes when attempting validation of previously reported genetic associations. Initial studies may be false positives or may propose a stronger genetic effect than subsequently found to be the case.

  13. Quality assessment of an interferon-gamma release assay for tuberculosis infection in a resource-limited setting

    Directory of Open Access Journals (Sweden)

    Hang Nguyen TL

    2009-05-01

    Full Text Available Abstract Background When a test for diagnosis of infectious diseases is introduced in a resource-limited setting, monitoring quality is a major concern. An optimized design of experiment and statistical models are required for this assessment. Methods Interferon-gamma release assay to detect tuberculosis (TB infection from whole blood was tested in Hanoi, Viet Nam. Balanced incomplete block design (BIBD was planned and fixed-effect models with heterogeneous error variance were used for analysis. In the first trial, the whole blood from 12 donors was incubated with nil, TB-specific antigens or mitogen. In 72 measurements, two laboratory members exchanged their roles in harvesting plasma and testing for interferon-gamma release using enzyme linked immunosorbent assay (ELISA technique. After intervention including checkup of all steps and standard operation procedures, the second trial was implemented in a similar manner. Results The lack of precision in the first trial was clearly demonstrated. Large within-individual error was significantly affected by both harvester and ELISA operator, indicating that both of the steps had problems. After the intervention, overall within-individual error was significantly reduced (P Conclusion BIBD and analysis of fixed-effect models with heterogeneous variance are suitable and useful for objective and individualized assessment of proficiency in a multistep diagnostic test for infectious diseases in a resource-constrained laboratory. The action plan based on our findings would be worth considering when monitoring for internal quality control is difficult on site.

  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. Concordance of a point mutation 5' to the A gamma-globin gene with A gamma beta + hereditary persistence of fetal hemoglobin in Greeks.

    Science.gov (United States)

    Waber, P G; Bender, M A; Gelinas, R E; Kattamis, C; Karaklis, A; Sofroniadou, K; Stamatoyannopoulos, G; Collins, F S; Forget, B G; Kazazian, H H

    1986-02-01

    In the Greek A gamma beta + type of hereditary persistence of fetal hemoglobin (HPFH), adult heterozygotes produce about 20% fetal hemoglobin (HbF), which is predominantly of the A gamma chain variety. The affected beta-globin gene cluster produces near normal amounts of beta-like globin, but in a A gamma to beta ratio of 20:80 instead of 0.5:99.5. Gelinas et al and Collins et al have shown a G to A change 117 nucleotides 5' to the A gamma gene in two Greeks with A gamma beta + HPFH. To demonstrate that this change is not a neutral polymorphism, we carried out hybridization with oligonucleotide probes (19mers) specific for the normal and the mutant sequences. While normal probe identified the A gamma fragment in genomic DNA of all subjects studied, mutant probe was positive only in Greeks with A gamma beta + HPFH. In sum, 108 beta-globin gene clusters of individuals without HPFH were negative when tested with mutant probe, but all 11 affected individuals of six families with Greek A gamma beta + HPFH (two previously sequenced and four new families) were positive with mutant probe. These data support the conclusion that the -117 mutation is causative of A gamma beta + HPFH in Greeks.

  16. Calcineurin antagonists inhibit interferon-gamma production by downregulation of interleukin-18 in human mixed lymphocyte reactions.

    Directory of Open Access Journals (Sweden)

    Kuinose M

    2000-10-01

    Full Text Available Tacrolimus (FK-506 and cyclosporin A (CsA are calcineurin antagonists used widely as T-cell immunosuppressants; however, their relative efficacy on the production of interleukin-18 (IL-18 remains undefined. We have examined the effects of FK-506 and CsA on the cytokine generation of human peripheral blood mononuclear cells (PBMCs in mixed lymphocyte reaction (MLR with lipopolysaccharide (LPS. We studied the levels of interleukin-18 (IL-18, IL-12, IL-10, IL-6, IL-2 and interferon-gamma (IFN-gamma in the supernatant in allo-MLR by ELISA assay. Supernatant levels of IFN-gamma, IL-2, IL-6, IL-10 and IL-12 were detected 12 h after MLR and markedly increased thereafter. In contrast, production of IL-18 was detected at 12 h, reached a near maximum level at 24 h and decreased at 72 h. These results suggested that IFN-gamma production depended on IL-18, IL-12 and IL-2 in the early phase of MLR and depended mainly on IL-12 and IL-2 in the late phase. Both calcineurin antagonists inhibit the generation of IL-18, which plays a large role in allogeneic cell interactions, in macrophages and they also promote an equivalent down-regulation of T helper 1 (Th1 and Th2 responses in a concentration-dependent manner. About 90% of IFN-gamma production induced by MLR was inhibited by an anti-IL-18 antibody, showing that IL-18 can trigger IFN-gamma production in MLR. These results suggest that dual signaling consisting of antigen-driven nuclear factor of activated T cells (NFAT activation and LPS-mediated NF-kappaB activation is crucial for IL-18 production in macrophages, and that IL-18 can trigger IFN-gamma production in T-cells by MLR.

  17. Inclusion phenomena of clove oil with alpha-, beta-, gamma- and heptakis (2,6-di-O-methyl)-beta-cyclodextrin.

    Science.gov (United States)

    Song, L X; Xu, P; Wang, H M; Yang, Y

    2009-01-01

    Inclusion interactions of alpha-, beta-, gamma- and heptakis (2,6-di-O-methyl)-beta-cyclodextrin (DMbeta-CD) as hosts with clove oil (an impure eugenol, I-Eug) as guest in aqueous solution were investigated by fluorescence emission spectra. The binding constants of different hosts to I-Eug in aqueous solution decreased in the order: gamma- > beta- > DMbeta- > alpha-CD. Two solid supramolecular inclusion complexes, I-Eug-beta-CD and I-Eug-gamma-CD, were prepared and characterised by nuclear magnetic resonance, powder X-ray diffraction, infrared spectroscopy, and thermogravimetric analysis. All the results proved the formation of I-Eug-CD. The inclusion differences between I-Eug and pure eugenol were discussed. The relative contents of the main component eugenol (Eug), second component (eugenol acetate, Eua) and others in I-Eug were found to be fairly different before and after being included by beta-CD, according to the data obtained from high performance liquid chromatography. This could be a practical method to extract the effective components (Eug and Eua) from I-Eug.

  18. Gamma-soft Analog of the Confined Beta-soft Rotor Model

    CERN Document Server

    Bonatsos, D; Pietralla, N; Terziev, P A

    2006-01-01

    A gamma-soft analog of the confined beta-soft (CBS) rotor model is developed, by using a gamma-independent displaced infinite well beta-potential in the Bohr Hamiltonian, for which exact separation of variables is possible. Level schemes interpolating between the E(5) critical point symmetry (with R(4/2)=E(4)/E(2)= 2.20) and the O(5) gamma-soft rotor (with R(4/2)=2.50) are obtained, exhibiting a crossover of excited 0+ bandheads which leads to agreement with the general trends of first excited 0+ states in this region and is observed experimentally in 128-Xe and 130-Xe.

  19. Cotinine and interferon-gamma levels in pre-school children exposed to household tobacco smoke

    Directory of Open Access Journals (Sweden)

    Lina Kalalo

    2013-09-01

    Full Text Available Background Environmental tobacco smoke has been consistently linked to negative health outcomes, especially in children, including an increased susceptibility to infections. Cigarette smoking has a depressive effect on interferon-γ (IFN-γ. Serum cotinine is a marker of exposure to smoke. Objective To determine the association between serum cotinine and interferon-γ (IFN-γ levels in children with household tobacco smoke exposure. Methods We conducted a cross-sectional study at the Tumumpa and Singkil Districts of Manado, Indonesia, from February to May 2012. Subjects were collected by consecutively sampling of healthy children aged 1-3 years who came to the integrated health posts. Seventy-four children were recruited and consisted of two groups of 37 subjects each, the tobacco smoke exposure group and the non-tobacco smoke exposure group. Blood specimens were collected from all subjects for laboratory blood tests of cotinine and IFN-γ levels. Results were analyzed by T-test and Pearson’s correlation analysis with a P<0.05 is considered as statistically significant. Results There was no significant correlation between serum cotinine and interferon-γ levels in the tobacco smoke exposure group. However, the interferon-γ level in the tobacco smoke exposure group was significantly lower than that of the non-tobacco smoke exposure group (P<0.0001. Conclusion Cotinine is not related to the interferon-γ level in children exposed to tobacco smoke, however, the interferon-γ level in children with tobacco smoke exposure is lower than in the non-tobacco smoke exposure group. [Paediatr Indones. 2013;53:287-90.].

  20. 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

  1. Effects of. gamma. -irradiation on. beta. -pinene content and germination in grapefruit

    Energy Technology Data Exchange (ETDEWEB)

    Uchiyama, Sadao; Kawamura, Yoko; Saito, Yukio; Nagashima, Kimiyo.

    1988-12-01

    Effects of ..gamma..-irradiation on ..beta..-pinene content and germination in grapefruit were investigated in order to develop a method to identify ..gamma..-irradiated grapefruit. ..beta..-Pinene is a component of essential oil in grapefruit and was reported to be susceptible to ..gamma..-irradiation. However, it was not degraded by irradiation (30 to 200 krad) in this experiment. When grapefruit irradiated at 50 krad were stored at 10degC for 2 months, no change of ..beta..-pinene content was found. ..beta..-Pinene itself was also stable to ..gamma..-irradiation at 1 Mrad. Thus, identification of irradiated grapefruit from the amount of ..beta..-pinene was impossible. On the other hand, the effect of ..gamma..-irradiation on radicle elongation was small but that on plumule expansion was so large as to prevent shooting in grapefruit irradiated even at 30 krad. Therefore it should be possible to identify ..gamma..-irradiated grapefruit by a germination method.

  2. Beta-delayed gamma decay of 26P: Possible evidence of a proton halo

    CERN Document Server

    Pérez-Loureiro, D; Bennett, M B; Liddick, S N; Bowe, A; Brown, B A; Chen, A A; Chipps, K A; Cooper, N; Irvine, D; McNeice, E; Montes, F; Naqvi, F; Ortez, R; Pain, S D; Pereira, J; Prokop, C J; Quaglia, J; Quinn, S J; Sakstrup, J; Santia, M; Schwartz, S B; Shanab, S; Simon, A; Spyrou, A; Thiagalingam, E

    2016-01-01

    Background: Measurements of $\\beta$ decay provide important nuclear structure information that can be used to probe isospin asymmetries and inform nuclear astrophysics studies. Purpose: To measure the $\\beta$-delayed $\\gamma$ decay of $^{26}$P and compare the results with previous experimental results and shell-model calculations. Method: A $^{26}$P fast beam produced using nuclear fragmentation was implanted into a planar germanium detector. Its $\\beta$-delayed $\\gamma$-ray emission was measured with an array of 16 high-purity germanium detectors. Positrons emitted in the decay were detected in coincidence to reduce the background. Results: The absolute intensities of $^{26}$P $\\beta$-delayed $\\gamma$-rays were determined. A total of six new $\\beta$-decay branches and 15 new $\\gamma$-ray lines have been observed for the first time in $^{26}$P $\\beta$-decay. A complete $\\beta$-decay scheme was built for the allowed transitions to bound excited states of $^{26}$Si. $ft$ values and Gamow-Teller strengths were a...

  3. A simultaneous beta and coincidence-gamma imaging system for plant leaves

    Science.gov (United States)

    Ranjbar, Homayoon; Wen, Jie; Mathews, Aswin J.; Komarov, Sergey; Wang, Qiang; Li, Ke; O’Sullivan, Joseph A.; Tai, Yuan-Chuan

    2016-05-01

    Positron emitting isotopes, such as 11C, 13N, and 18F, can be used to label molecules. The tracers, such as 11CO2, are delivered to plants to study their biological processes, particularly metabolism and photosynthesis, which may contribute to the development of plants that have a higher yield of crops and biomass. Measurements and resulting images from PET scanners are not quantitative in young plant structures or in plant leaves due to poor positron annihilation in thin objects. To address this problem we have designed, assembled, modeled, and tested a nuclear imaging system (simultaneous beta–gamma imager). The imager can simultaneously detect positrons ({β+} ) and coincidence-gamma rays (γ). The imaging system employs two planar detectors; one is a regular gamma detector which has a LYSO crystal array, and the other is a phoswich detector which has an additional BC-404 plastic scintillator for beta detection. A forward model for positrons is proposed along with a joint image reconstruction formulation to utilize the beta and coincidence-gamma measurements for estimating radioactivity distribution in plant leaves. The joint reconstruction algorithm first reconstructs beta and gamma images independently to estimate the thickness component of the beta forward model and afterward jointly estimates the radioactivity distribution in the object. We have validated the physics model and reconstruction framework through a phantom imaging study and imaging a tomato leaf that has absorbed 11CO2. The results demonstrate that the simultaneously acquired beta and coincidence-gamma data, combined with our proposed joint reconstruction algorithm, improved the quantitative accuracy of estimating radioactivity distribution in thin objects such as leaves. We used the structural similarity (SSIM) index for comparing the leaf images from the simultaneous beta–gamma imager with the ground truth image. The jointly reconstructed images yield SSIM indices of 0.69 and 0.63, whereas

  4. 1. cap alpha. ,25-Dihydroxyvitamin D/sub 3/ inhibits. gamma. -interferon synthesis by normal human peripheral blood lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Reichel, H.; Koeffler, H.P.; Tobler, A.; Norman, A.W.

    1987-05-01

    1..cap alpha..,25-Dihydroxyvitamin D/sub 3/ (1,25-(OH)/sub 2/D/sub 3/), the biologically active metabolite of vitamin D/sub 3/, inhibited synthesis of ..gamma..-interferon (IFN-..gamma..) by phytohemagglutinin-activated peripheral blood lymphocytes (PBLs). A significant reduction of IFN-..gamma.. protein levels in PBL culture medium was achieved with a physiologic 1,25-(OH)/sub 2/D/sub 3/ concentration, 1,25-(OH)/sub 2/D/sub 3/ also inhibited accumulation of IFN-..gamma.. mRNA in activated PBLs in a dose-dependent fashion. The ability of 1,25-(OH)/sub 2/D/sub 3/ to modulate IFN-..gamma.. protein synthesis was unaltered in the presence of high concentrations of recombinant human interleukin 2. The suppression of IFN-..gamma.. synthesis by PBLs was specific for 1,25-(OH)/sub 2/D/sub 3/; the potencies of other vitamin D/sub 3/ metabolites were correlated with their affinities for the cellular 1,25-(OH)/sub 2/D/sub 3/ receptor. The time course of 1,25-(OH)/sub 2/D/sub 3/ receptor expression in phytohemagglutinin-activated PBLs was correlated with the time course of 1,25-(OH)/sub 2/D/sub 3/-mediated inhibition of IFN-..gamma.. synthesis. Finally, the authors examined the effects of 1,25-(OH)/sub 2/D/sub 3/ on the constitutive IFN-..gamma.. production by two human T-lymphocyte lines transformed by human T-lymphotropic virus type I. The cell lines were established from a normal donor (cell line S-LB1) and from a patient with vitamin D-dependent rickets type 2 (cell line Ab-VDR). IFN-..gamma.. synthesis by S-LB1 cells was inhibited in a dose-dependent fashion by 1,25-(OH)/sub 2/D/sub 3/, whereas IFN-..gamma.. synthesis by Ab-VDR cells was not altered by 1,25-(OH)/sub 2/D/sub 3/. The data presented in this study provide evidence for a role of 1,25-(OH)/sub 2/D/sub 3/ in immunoregulation.

  5. Animal experiment and clinical study of effect of gamma-interferon on hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Hong Lei Weng; Wei Min Cai; Rong Hua Liu

    2001-01-01

    AIM To evaluate the antifibrotic effect ofdifferent doses of recombinant human Gamma-Interferon (IFN-γ) intwo rat models of hepaticfibrosis, and to observe its effect on moderatechronic hepatitis B virus fibrosis.METNODS Hepatic fibrosis was successfullyinduced in 150 and 196 rats by subcutaneousinjection of carbon tetrachloride (CCl4) andintraperitoneal injection of dimethylnitrosamine(DMN), respectively. Each of the two modeldose IFN-γ group (15 MU/kg per day, i.m. for 8group (1.67 MU/kg daily, i.m. for 8 weeks).Another group of 10 rats without any treatmentwas used as normal controls. At the end of theexperiment, semi-quantitative histopathologicalscores of inflammation and fibrosis, liver (αsmooth muscle actin (α-SMA) expression level,liver hydroxyl proline content and serumhyaluronic acid levels were compared. And 47medium chronic hepatitis B viral fibrosispatients were studied. They were given IFN-γtreatment, 100MU/day i.m. for the first threemonths and 100MU qod i.m. for the next sixmonths. Semi-quantitative pathological scoresof inflammation and fibrosis and serum hepaticfibrosis indices were compared within the 9months.RESULTS In animal experiment, thepathological fibrosis scores and liver hydroxylproline content were found to be significantlylower in rats treated with different doses of IFN-γ as compared with rats in fibrotic model groupinduced by either CCI4 or DMN, in a dose-dependent manner. For CCI4-induced model,pathological fibrosis scores in high, medium andIow doses IFN-γ groups were 5.10 ± 2.88, 7.70 ±3.53 and 8.00 ± 3.30, respectively, but the scorewas 14.60 ± 7.82 in fibrotic model group.Hydroxyl proline contents were 2.83 ± 1.18, 3.59± 1.22 and 4.80 ± 1.62, in the three IFN-γgroups, and 10.01 ± 3.23 in fibrotic model group.The difference was statistically significant(P<0.01). Similar results were found in DMN-induced model. Pathological fibrosis scoreswere 6.30±0.48, 8.10 ±2.72 and 8.30 ±2.58, inhigh, medium and Iow doses

  6. The effectiveness of parallel gamma-interferon testing in New Zealand's bovine tuberculosis eradication programme.

    Science.gov (United States)

    Sinclair, J A; Dawson, K L; Buddle, B M

    2016-05-01

    In bovine tuberculosis (bTB) eradication programmes, especially where prevalence is low, sensitivity of testing in infected herds must be maximised to reduce the possibility of recrudescence of prior infection and the risk to other herds via animal movement. The gamma-interferon (γ-IFN) assay applied in parallel with intradermal tuberculin testing has been shown to increase test sensitivity. The aim of this work was to substantiate this effect in the field. A retrospective observational study was conducted on 239 New Zealand cattle breeding and dairy herds with bTB infection between 1 July 2011 and 1 September 2015 to evaluate the outcomes of new policy introduced in 2011. The investigation defined the number and proportion of reactors (animals testing positive and slaughtered) found with lesions of bTB in intradermal caudal fold testing (CFT) and parallel γ-IFN testing, at the breakdown test or first whole herd test after breakdown, WHT(1), and at the final or projected final whole herd test, WHT(F). Parallel γ-IFN testing was used in 26.8% of the 239 herds at WHT(1), and 430 animals in 49 herds were deemed reactors. One hundred and sixty (37.2%) of these reactors from 32 herds were found to have bTB lesions, despite having been negative to caudal fold testing. These 160 infected animals accounted for 29.6% of all infection found at WHT(1). At WHT(F), parallel γ-IFN testing was conducted on 93 herds and detected a total of 122 reactors in 49 herds, in addition to those found by CFT. Twenty-one of these reactors, from 13 herds, had bTB lesions at slaughter, accounting for 67.7% of all reactors found with bTB at WHT(F). Eleven of these 13 herds would have had their movement restrictions revoked based on a negative herd CFT alone, and could potentially have caused outward transmission of bTB to other herds, as well as experiencing recrudescent breakdowns. We conclude that γ-IFN testing in infected herds, in parallel with intradermal tuberculin testing, is a

  7. The effectiveness of parallel gamma-interferon testing in New Zealand's bovine tuberculosis eradication programme.

    Science.gov (United States)

    Sinclair, J A; Dawson, K L; Buddle, B M

    2016-05-01

    In bovine tuberculosis (bTB) eradication programmes, especially where prevalence is low, sensitivity of testing in infected herds must be maximised to reduce the possibility of recrudescence of prior infection and the risk to other herds via animal movement. The gamma-interferon (γ-IFN) assay applied in parallel with intradermal tuberculin testing has been shown to increase test sensitivity. The aim of this work was to substantiate this effect in the field. A retrospective observational study was conducted on 239 New Zealand cattle breeding and dairy herds with bTB infection between 1 July 2011 and 1 September 2015 to evaluate the outcomes of new policy introduced in 2011. The investigation defined the number and proportion of reactors (animals testing positive and slaughtered) found with lesions of bTB in intradermal caudal fold testing (CFT) and parallel γ-IFN testing, at the breakdown test or first whole herd test after breakdown, WHT(1), and at the final or projected final whole herd test, WHT(F). Parallel γ-IFN testing was used in 26.8% of the 239 herds at WHT(1), and 430 animals in 49 herds were deemed reactors. One hundred and sixty (37.2%) of these reactors from 32 herds were found to have bTB lesions, despite having been negative to caudal fold testing. These 160 infected animals accounted for 29.6% of all infection found at WHT(1). At WHT(F), parallel γ-IFN testing was conducted on 93 herds and detected a total of 122 reactors in 49 herds, in addition to those found by CFT. Twenty-one of these reactors, from 13 herds, had bTB lesions at slaughter, accounting for 67.7% of all reactors found with bTB at WHT(F). Eleven of these 13 herds would have had their movement restrictions revoked based on a negative herd CFT alone, and could potentially have caused outward transmission of bTB to other herds, as well as experiencing recrudescent breakdowns. We conclude that γ-IFN testing in infected herds, in parallel with intradermal tuberculin testing, is a

  8. A differential scanning calorimetry study of the kinetics of the {beta} {yields} {gamma} phase transformation in plutonium

    Energy Technology Data Exchange (ETDEWEB)

    Ennaceur, S.M., E-mail: Sue.Ennaceur@awe.co.uk [AWE, Aldermaston, Reading, Berkshire RG7 4PR (United Kingdom)

    2012-11-10

    Highlights: Black-Right-Pointing-Pointer Significant impact of thermal history on {beta} {yields} {gamma} phase transformation parameters. Black-Right-Pointing-Pointer Stability of the parent {beta}-phase on the kinetics of the {beta} {yields} {gamma} phase transformation. Black-Right-Pointing-Pointer Comparison of {beta} {yields} {gamma} transformation parameters for {beta}-phase formed from {alpha}-phase and from {gamma}-phase. Black-Right-Pointing-Pointer Comparison of {beta} {yields} {gamma} reaction kinetics for {beta}-phase formed from {alpha}-phase and from {gamma}-phase. Black-Right-Pointing-Pointer Impact of {beta}-phase condition on the reaction parameters for the {beta} {yields} {alpha} phase transformation. - Abstract: A number of DSC studies have determined the onset temperature and the enthalpy change for the {beta} {yields} {gamma} phase transformation in plutonium but these have all been conducted by measuring the phase transformation parameters immediately following the {alpha} {yields} {beta} phase transformation which will have a considerable impact on the reaction kinetics. The thermal history and condition of a specimen will have a significant effect on the reaction parameters of a solid phase transformation. The current study examines the influence of the specimen condition and more specifically the impact of a previous phase transformation and the mode of formation of the {beta}-phase from both the {alpha}-phase and from the {gamma}-phase on the {beta} {yields} {gamma} phase transformation parameters and reaction kinetics. The impact of the {beta}-phase condition on the transformation parameters of the {beta} {yields} {alpha} phase transformation is also examined.

  9. Measurements of $L_{31}, L_{3}\\alpha, L_{3}\\beta, L_{2}\\beta, L_{2} \\gamma, L_{1}\\beta, L_{1}\\gamma, L_{\\beta}, L_{\\gamma}, L_{1x}, L_{2x}$ and $L_{3x}$ X-ray production cross sections and L subshell fluorescence

    CERN Document Server

    Ertugrul, M

    2001-01-01

    The L/sub 3l/, L/sub 3 alpha /, L/sub 3 beta /, L/sub 2 beta /, L/sub 2 gamma /, L/sub 1 beta /, L/sub 1 gamma /, L/sub beta /, L/sub gamma /, L/sub 1x/, L/sub 2x/ and L/sub 3x/ X-ray production cross sections in Re, W and Ta have been measured using the 59.5 keV incident photon energy. The measurements were performed using an Am-241 radioisotope as the photon source and a Si(Li) detector. The L X-rays are resolved with a new analytical method. The obtained L/sub l/, L/sub alpha /, L /sub 3 beta /, L/sub 2 beta /, L/sub 2 gamma /, L/sub 1 beta /, L/sub 1 gamma /, L/sub beta /, L/sub gamma /, L/sub 1x/, L/sub 2x/ and L /sub 3x/ X-rays are compared with the theoretical calculations using the most reliable theoretical values of L/sub i/ (i=1, 2, 3) subshell photoionization cross sections, fluorescence yields, X-ray emission rates and Coster-Kronig transition probabilities. The results in the present paper are found to be in good agreement with the calculated values. (23 refs).

  10. Joint inflammation and chondrocyte death become independent of Fcgamma receptor type III by local overexpression of interferon-gamma during immune complex-mediated arthritis.

    NARCIS (Netherlands)

    Nabbe, K.C.A.M.; Boross, P.; Holthuysen, A.E.M.; Sloetjes, A.W.; Kolls, J.; Verbeek, S.; Lent, P.L.E.M. van; Berg, W.B. van den

    2005-01-01

    OBJECTIVE: It has previously been shown that the onset and the degree of joint inflammation during immune complex (IC)-mediated arthritis depend on Fcgamma receptor type III (FcgammaRIII). Local adenoviral overexpression of interferon-gamma (IFNgamma) in the knee joint prior to onset of IC-mediated

  11. Tuberculosis screening in patients with psoriasis before antitumour necrosis factor therapy : comparison of an interferon-gamma release assay vs. tuberculin skin test

    NARCIS (Netherlands)

    Laffitte, E.; Janssens, J. P.; Roux-Lombard, P.; Thielen, A. M.; Barde, C.; Marazza, G.; Panizzon, R. G.; Saurat, J-H.

    2009-01-01

    Background Antitumour necrosis factor (anti-TNF) treatments may reactivate latent tuberculosis infection (LTBI). For detecting LTBI, the tuberculin skin test (TST) has low sensitivity and specificity. Interferon-gamma release assays (IGRA) have been shown to be more sensitive and specific than TST.

  12. Impairment of natural killer cell activity in Indian kala-azar: restoration of activity by interleukin 2 but not by alpha or gamma interferon.

    OpenAIRE

    Manna, P P; Bharadwaj, D.; Bhattacharya, S.; Chakrabarti, G; Basu, D; Mallik, K K; Bandyopadhyay, S.

    1993-01-01

    Indian kala-azar patients have normal numbers of peripheral blood NK cells but impaired functional activity due to decreased binding and lysis of target cells. This impairment of NK activity could not be corrected by exogenous recombinant human alpha or gamma interferon. However, recombinant human interleukin 2 was able to restore this activity by augmenting conjugate formation and lysis of target cells.

  13. Procedure for the elaboration of extended sources beta and/or gamma emitting; Procedimiento para la elaboracion de fuentes extendidas emisoras beta y/o gamma

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-12-15

    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{sup 2} and the other one of 100 cm{sup 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)

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

    International Nuclear Information System (INIS)

    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 (37Cs and 60Co), and some of them were tested in beta radiation (90Sr+9'0Y e 204Tl) 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)

  15. Interferon-beta increases systemic BAFF levels in multiple sclerosis without increasing autoantibody production

    DEFF Research Database (Denmark)

    Hedegaard, Chris J; Sellebjerg, Finn; Krakauer, Martin;

    2011-01-01

    -associated autoantibodies. Objective: To investigate whether BAFF levels are associated with disease severity/activity in untreated MS patients, and to assess the effect of IFN-beta therapy on circulating BAFF and anti-myelin basic protein (MBP) autoantibody levels. Results: Twenty-three patients with relapsing......-remitting MS (RRMS) were followed longitudinally from initiation of IFN-beta therapy. Their blood levels of BAFF correlated positively at baseline with the expanded disability status scale (p ...-enhanced lesions. The patients were followed for up to 26 months, during which the BAFF levels remained elevated without association to increased disease activity. IFN-beta therapy caused an increase in plasma BAFF levels after both 3 and 6 months of therapy (p

  16. 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.

  17. Clinical improvement in feline herpesvirus 1 infected cats by oral low dose of interleukin-12 plus interferon-gamma.

    Science.gov (United States)

    Fiorito, Filomena; Cantiello, Antonietta; Granato, Giovanna Elvira; Navas, Luigi; Diffidenti, Carmine; De Martino, Luisa; Maharajan, Veeramani; Olivieri, Fabio; Pagnini, Ugo; Iovane, Giuseppe

    2016-10-01

    Feline herpesvirus 1 (FHV-1) is a widespread cat pathogen inducing rhinitis, conjunctivitis and corneal ulcers. To alleviate acute FHV-1-induced disease, antiviral agents are used often with antibiotics. But sometimes, these treatments, as well as conventional doses of cytokines have moderate efficacy and/or collateral effects. Herein we have investigated the effects of low dose interleukin (IL)-12 plus interferon (IFN)-gamma, prepared by Sequential Kinetic Activated (SKA), on the treatment of FHV-1 infection. Twenty-five, unvaccinated FHV-1-positive cats were recruited into a prospective, randomized, placebo-controlled, double-blinded clinical trial. Fifteen cats were treated for 6 months with oral low doses of SKA IL-12 plus IFN-gamma and 10 cats were treated with placebo. At 1, 6 and 12 months (follow-up) after the beginning of treatment, clinical assessment, PCR assay and blood count were carried out. At follow-up, in treated group, we observed significant (p<0.05) improvements in clinical signs and PCR became negative in 12/15 cats (80%). In placebo, 10/10 cats were PCR-positive, with improvements (30%) or worsening (70%) in clinical signs. Blood values were normal in both groups. Our results show that the low dose therapy, based on activated solutions of IL-12 plus IFN-gamma, represents a novel approach to treat FHV-1 infection in cats. PMID:27638118

  18. Identification of alpha beta and gamma delta T cell receptor-positive cells

    DEFF Research Database (Denmark)

    Geisler, C; Larsen, J K; Plesner, T

    1988-01-01

    distribution and function of these different T cells. In immunofluorescence studies gamma delta TCR+ cells have been identified as CD3+WT-31- or CD3+CD4-CD8- cells. However, this may not be the optimal procedure because gamma delta TCR+ cells are weakly WT-31+, and some are CD8+. The aim of this study......Two lineages of T lymphocytes bearing the CD3 antigen can be defined on the basis of the nature of the heterodimeric receptor chain (alpha beta or gamma delta T cell receptor (TCR) expressed. Precise identification of alpha beta and gamma delta TCR+ cells is essential when studying the tissue...... was to evaluate a panel of monoclonal antibodies (MoAb) directed against different chains of the TCR-T3 complex for a more precise identification of alpha beta+ and gamma delta TCR+ cells in flow cytometric studies. We found that the MoAb anti-Ti-gamma A and delta-TCS-1, recognizing the TCR-gamma and the TCR...

  19. Expression of steroidogenic acute regulatory protein and its regulation by interferon-gamma in rat corpus luteum

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The steroidogenic acute regulatory protein (StAR) is the key regulatory protein of steroidogenesis. De novo synthesis of StAR protein is required for intramitochondrial translocation of cholesterol to the cytochrome P450 side chain cleavage enzyme which is located on the matrix side of the inner mitochondrial membrane. This is the rate-limiting step of steroid biosynthesis. Using in situ hybridization and immunohistochemistry we studied StAR expression in various stages of the corpora luteal and its regulation by interferon-gamma (IFNγ) in the adult pseudopregnant rat. The results indicated that expression of StAR in the corpora luteal was correlated with progesteron production and IFNγ was capable of inhibiting its expression.

  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

    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...... 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....... This aspect needs to be further investigated. Optimisation of the IFN-γ test on day-old samples for diagnosing MAP infected herds would facilitate the large scale use of this diagnostic test....

  1. 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;

    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....... The study included blood samples from 26 heifers of a MAP infected herd, collected three times with 4 and 5 week interval and blood samples from 60 heifers of a MAP non-infected herd collected once. The IFN-γ responses of the non-infected heifers were used to establish cut-off values for each antigen....... Animals of the MAP infected herd were grouped as cases or non-cases by a case definition that was: an animal with ≥2 positive tests for ≥4 antigens, which resulted in 13 cases and 13 non-cases. Based on the case-definition, immunogenicity and specificity of each antigen were calculated. IFN-γ levels...

  2. Physiological and receptor-selective retinoids modulate interferon gamma signaling by increasing the expression, nuclear localization, and functional activity of interferon regulatory factor-1.

    Science.gov (United States)

    Luo, Xin M; Ross, A Catharine

    2005-10-28

    Synergistic actions between all-trans-retinoic acid (atRA) and interferon gamma (IFNgamma) on modulation of cellular functions have been reported both in vitro and in vivo. However, the mechanism of atRA-mediated regulation of IFNgamma signaling is poorly understood. In this study, we have used the human lung epithelial cell line A549 to examine the effect of atRA on IFNgamma-induced expression of IFN regulatory factor-1 (IRF-1), an important transcription factor involved in cell growth and apoptosis, differentiation, and antiviral and antibacterial immune responses. At least 4 h of pretreatment with atRA followed by suboptimal concentrations of IFNgamma induced a faster, higher, and more stable expression of IRF-1 than IFNgamma alone. Actinomycin D completely blocked the induction of IRF-1 by the combination, suggesting regulation at the transcriptional level. Further, we found that activation of signal transducer and activator of transcription-1 was induced more dramatically by atRA and IFNgamma than by IFNgamma alone. Expression of IFNgamma receptor-1 on the cell surface was also increased upon atRA pretreatment. Experiments using receptor-selective retinoids revealed that ligands for retinoic acid receptor-alpha (RARalpha), including atRA, 9-cis-retinoic acid, and Am580, sequentially increased the levels of IFNgamma receptor-1, activated signal transducer and activator of transcription-1, and IRF-1 and that an RARalpha antagonist was able to inhibit the effects of atRA and Am580. In addition, atRA pretreatment affected the transcriptional functions of IFNgamma-induced IRF-1, increasing its nuclear localization and DNA binding activity as well as the transcript levels of IRF-1 target genes. These results suggest that atRA, an RARalpha ligand, regulates IFNgamma-induced IRF-1 by affecting multiple components of the IFNgamma signaling pathway, from the plasma membrane to the nuclear transcription factors.

  3. Cigarette-Smoking Intensity and Interferon-Gamma Release Assay Conversion among Persons Who Inject Drugs: A Cohort Study

    Directory of Open Access Journals (Sweden)

    Sanghyuk S. Shin

    2012-01-01

    Full Text Available We analyzed data from a longitudinal cohort study of persons who inject drugs (PWID in Tijuana, Mexico, to explore whether cigarette smoking increases the risk of interferon gamma release assay (IGRA conversion. PWID were recruited using respondent driven sampling (RDS. QuantiFERON-TB Gold In-Tube (QFT assay conversion was defined as interferon-gamma concentrations <0.35 IU/mL at baseline and ≥0.7 IU/mL at 18 months. We used multivariable Poisson regression adjusted for RDS weights to estimate risk ratios (RRs. Of 129 eligible participants, 125 (96.9% smoked at least one cigarette during followup with a median of 11 cigarettes smoked daily, and 52 (40.3% had QFT conversion. In bivariate analysis, QFT conversion was not associated with the number of cigarettes smoked daily (P=0.716. Controlling for age, gender, education, and alcohol use, the RRs of QFT conversion for smoking 6–10, 11–15, and ≥16 cigarettes daily compared to smoking 0–5 cigarettes daily were 0.9 (95% confidence interval (CI, 0.5–1.6, 0.5 (95% CI, 0.3–1.2, and 0.7 (95% CI, 0.3–1.6, respectively. Although this study did not find an association between self-reported smoking intensity and QFT conversion, it was not powered sufficiently to negate such an association. Larger longitudinal studies are needed to fully explore this relationship.

  4. 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 beta-1b 250 microg (n=292; early treatment) or placebo (n=176; delayed treatment) subcutaneously every other day for 2 years, or until diagnosis of CDMS. All patients were then eligible to enter a prospectively planned follow-up phase with open-label interferon beta-1b up to a maximum of 5 years...... 125 in both groups. No significant differences in other disability related outcomes were recorded. Frequency and severity of adverse events remained within the established safety and tolerability profile of interferon beta-1b. INTERPRETATION: Effects on the rate of conversion to CDMS and the...

  5. Biosynthesis of Tcr-alpha, beta and Tcr-gamma, delta/CD3 complexes

    DEFF Research Database (Denmark)

    Bauguil-Caspar, S; Arnaud, J; Kuhlmann, J;

    1993-01-01

    Jurkat J76 clone, LYON L12.37 clone and L12.37 cells transfected with J76-alpha cDNA or J76 Tcr-alpha mutated cDNA (J79) were analysed for membrane expression of Tcr/CD3 complex using WT31 mAb (Tcr-alpha, beta) or Tcr-delta 1 mAb (Tcr-gamma, delta): LYON cells express V beta 9 bearing Tcr-beta...... chains. J76 Tcr-alpha cDNA transfected LYON cells have intracellular Tcr-gamma, delta chains and J79 Tcr-alpha cDNA transfected LYON cells have intracellular Tcr-alpha (M), beta chains....

  6. Alzheimer Disease: Crosstalk between the Canonical Wnt/Beta-Catenin Pathway and PPARs Alpha and Gamma

    Science.gov (United States)

    Vallée, Alexandre; Lecarpentier, Yves

    2016-01-01

    The molecular mechanisms underlying the pathophysiology of Alzheimer's disease (AD) are still not fully understood. In AD, Wnt/beta-catenin signaling has been shown to be downregulated while the peroxisome proliferator-activated receptor (PPAR) gamma (mARN and protein) is upregulated. Certain neurodegenerative diseases share the same Wnt/beta-catenin/PPAR gamma profile, such as bipolar disorder and schizophrenia. Conversely, other NDs share an opposite profile, such as amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, multiple sclerosis, and Friedreich's ataxia. AD is characterized by the deposition of extracellular Abeta plaques and the formation of intracellular neurofibrillary tangles in the central nervous system (CNS). Activation of Wnt signaling or inhibition of both glycogen synthase kinase-3beta and Dickkopf 1, two key negative regulators of the canonical Wnt pathway, are able to protect against Abeta neurotoxicity and to ameliorate cognitive performance in AD patients. Although PPAR gamma is upregulated in AD patients, and despite the fact that it has been shown that the PPAR gamma and Wnt/beta catenin pathway systems work in an opposite manner, PPAR gamma agonists diminish learning and memory deficits, decrease Abeta activation of microglia, and prevent hippocampal and cortical neurons from dying. These beneficial effects observed in AD transgenic mice and patients might be partially due to the anti-inflammatory properties of PPAR gamma agonists. Moreover, activation of PPAR alpha upregulates transcription of the alpha-secretase gene and represents a new therapeutic treatment for AD. This review focuses largely on the behavior of two opposing pathways in AD, namely Wnt/beta-catenin signaling and PPAR gamma. It is hoped that this approach may help to develop novel AD therapeutic strategies integrating PPAR alpha signaling.

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

    International Nuclear Information System (INIS)

    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 (60Co) and chronic (137Cs) gamma radiation and internal beta radiation (32P), lethality (LD50, LD100), growth inhibition, and chromosome aberrations were investigated. The LD50 and LD100 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. 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

  9. Diffusional transport during the cyclic oxidation of gamma + beta, Ni-Cr-Al(Y, Zr) alloys

    Science.gov (United States)

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

    1988-01-01

    The cyclic oxidation behavior of several cast gamma + beta, Ni-Cr-Al(Y, Zr) alloys and one low-pressure plasma spraying gamma + beta, Ni-Co-Cr-Al(Y) alloy was studied. Cyclic oxidation was found to result in a decreasing Al concentration at the oxide-metal interface due to a high rate of Al consumption coupled with oxide scale cracking and spalling. Diffusion paths plotted on the ternary phase diagram showed higher Ni concentrations with increasing cyclic oxidation exposures. The alloy with the highest rate of Al consumption and the highest Al content underwent breakaway oxidation following 500 1-hr cycles at 1200 C.

  10. Pre-stimulus beta and gamma oscillatory power predicts perceived audiovisual simultaneity.

    Science.gov (United States)

    Yuan, Xiangyong; Li, Haijiang; Liu, Peiduo; Yuan, Hong; Huang, Xiting

    2016-09-01

    Pre-stimulus oscillation activity in the brain continuously fluctuates, but it is correlated with subsequent behavioral and perceptual performance. Here, using fast Fourier transformation of pre-stimulus electroencephalograms, we explored how oscillatory power modulates the subsequent discrimination of perceived simultaneity from non-simultaneity in the audiovisual domain. We found that the over-scalp high beta (20-28Hz), parieto-occipital low beta (14-20Hz), and high gamma oscillations (55-80Hz) were significantly stronger before audition-then-vision sequence when they were judged as simultaneous rather than non-simultaneous. In contrast, a broad range of oscillations, mainly the beta and gamma bands over a great part of the scalp were significantly weaker before vision-then-audition sequences when they were judged as simultaneous versus non-simultaneous. Moreover, for auditory-leading sequence, pre-stimulus beta and gamma oscillatory power successfully predicted subjects' reports of simultaneity on a trial-by-trial basis, with stronger activity resulting in more simultaneous judgments. These results indicate that ongoing fluctuations of beta and gamma oscillations can modulate subsequent perceived audiovisual simultaneity, but with an opposing pattern for auditory- and visual-leading sequences. PMID:27393081

  11. Pre-stimulus beta and gamma oscillatory power predicts perceived audiovisual simultaneity.

    Science.gov (United States)

    Yuan, Xiangyong; Li, Haijiang; Liu, Peiduo; Yuan, Hong; Huang, Xiting

    2016-09-01

    Pre-stimulus oscillation activity in the brain continuously fluctuates, but it is correlated with subsequent behavioral and perceptual performance. Here, using fast Fourier transformation of pre-stimulus electroencephalograms, we explored how oscillatory power modulates the subsequent discrimination of perceived simultaneity from non-simultaneity in the audiovisual domain. We found that the over-scalp high beta (20-28Hz), parieto-occipital low beta (14-20Hz), and high gamma oscillations (55-80Hz) were significantly stronger before audition-then-vision sequence when they were judged as simultaneous rather than non-simultaneous. In contrast, a broad range of oscillations, mainly the beta and gamma bands over a great part of the scalp were significantly weaker before vision-then-audition sequences when they were judged as simultaneous versus non-simultaneous. Moreover, for auditory-leading sequence, pre-stimulus beta and gamma oscillatory power successfully predicted subjects' reports of simultaneity on a trial-by-trial basis, with stronger activity resulting in more simultaneous judgments. These results indicate that ongoing fluctuations of beta and gamma oscillations can modulate subsequent perceived audiovisual simultaneity, but with an opposing pattern for auditory- and visual-leading sequences.

  12. The effect of interferon-beta on black holes in patients with multiple sclerosis.

    Science.gov (United States)

    Bagnato, Francesca; Evangelou, Iordanis E; Gallo, Antonio; Gaindh, Deeya; Yao, Karen

    2007-07-01

    Multiple sclerosis (MS) is an immunological disorder of the CNS. Linked to an initial transient inflammation as the result of blood-brain barrier leakage, the disease progresses into a neurodegenerative phase. MRI is the most powerful paraclinical tool for diagnosing and monitoring MS. Although contrast enhancing lesions are the visible events of blood-brain barrier breakdown, accumulation of hypointense lesions, namely black holes, are recognised as irreversible axonal loss. IFN-beta is administered as a first-line drug in MS patients. However, whether the effect of IFN-beta extends beyond just prevention of blood-brain barrier leakage and further prevents the formation of black holes or promotes their recovery once formed, is not yet understood. PMID:17665995

  13. Role of beta-oxidation enzymes in gamma-decalactone production by the yeast Yarrowia lipolytica.

    Science.gov (United States)

    Waché, Y; Aguedo, M; Choquet, A; Gatfield, I L; Nicaud, J M; Belin, J M

    2001-12-01

    Some microorganisms can transform methyl ricinoleate into gamma-decalactone, a valuable aroma compound, but yields of the bioconversion are low due to (i) incomplete conversion of ricinoleate (C(18)) to the C(10) precursor of gamma-decalactone, (ii) accumulation of other lactones (3-hydroxy-gamma-decalactone and 2- and 3-decen-4-olide), and (iii) gamma-decalactone reconsumption. We evaluated acyl coenzyme A (acyl-CoA) oxidase activity (encoded by the POX1 through POX5 genes) in Yarrowia lipolytica in lactone accumulation and gamma-decalactone reconsumption in POX mutants. Mutants with no acyl-CoA oxidase activity could not reconsume gamma-decalactone, and mutants with a disruption of pox3, which encodes the short-chain acyl-CoA oxidase, reconsumed it more slowly. 3-Hydroxy-gamma-decalactone accumulation during transformation of methyl ricinoleate suggests that, in wild-type strains, beta-oxidation is controlled by 3-hydroxyacyl-CoA dehydrogenase. In mutants with low acyl-CoA oxidase activity, however, the acyl-CoA oxidase controls the beta-oxidation flux. We also identified mutant strains that produced 26 times more gamma-decalactone than the wild-type parents. PMID:11722925

  14. Treatment of marrow stroma with interferon-alpha restores normal beta 1 integrin-dependent adhesion of chronic myelogenous leukemia hematopoietic progenitors. Role of MIP-1 alpha.

    OpenAIRE

    R Bhatia; McGlave, P B; Verfaillie, C M

    1995-01-01

    The mechanisms by which interferon-alpha (IFN-alpha) restores normal hematopoiesis in chronic myelogenous leukemia (CML) are not well understood. We have recently demonstrated that IFN-alpha acts directly on CML hematopoietic progenitors to restore their adhesion to marrow stroma by modulating beta 1 integrin receptor function. In the present study we examined the effect of IFN-alpha treatment of marrow stroma on subsequent adhesion of CML progenitors. Stromal layers were preincubated with IF...

  15. Interferon-Beta Therapy of Multiple Sclerosis Patients Improves the Responsiveness of T Cells for Immune Suppression by Regulatory T Cells

    OpenAIRE

    Bettina Trinschek; Felix Luessi; Catharina C. Gross; Heinz Wiendl; Helmut Jonuleit

    2015-01-01

    Multiple sclerosis (MS) is an inflammatory autoimmune disease characterized by imbalanced immune regulatory networks, and MS patient-derived T effector cells are inefficiently suppressed through regulatory T cells (Treg), a phenomenon known as Treg resistance. In the current study we investigated T cell function in MS patients before and after interferon-beta therapy. We compared cytokine profile, responsiveness for Treg-mediated suppression ex vivo and evaluated reactivity of T cells in vi...

  16. Interferon-Beta Therapy of Multiple Sclerosis Patients Improves the Responsiveness of T Cells for Immune Suppression by Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Bettina Trinschek

    2015-07-01

    Full Text Available Multiple sclerosis (MS is an inflammatory autoimmune disease characterized by imbalanced immune regulatory networks, and MS patient-derived T effector cells are inefficiently suppressed through regulatory T cells (Treg, a phenomenon known as Treg resistance. In the current study we investigated T cell function in MS patients before and after interferon-beta therapy. We compared cytokine profile, responsiveness for Treg-mediated suppression ex vivo and evaluated reactivity of T cells in vivo using a humanized mouse model. We found that CD4+ and CD8+ T cells of therapy-naive MS patients were resistant to Treg-mediated suppression. Treg resistance is associated with an augmented IL-6 production, enhanced IL-6 receptor expression, and increased PKB/c-Akt phosphorylation. These parameters as well as responsiveness of T cells to Treg-mediated suppression were restored after interferon-beta therapy of MS patients. Following transfer into immunodeficient mice, MS T cells induced a lethal graft versus host disease (GvHD and in contrast to T cells of healthy volunteers, this aggressive T cell response could not be controlled by Treg, but was abolished by anti-IL-6 receptor antibodies. However, magnitude and lethality of GvHD induced by MS T cells was significantly decreased after interferon-beta therapy and the reaction was prevented by Treg activation in vivo. Our data reveals that interferon-beta therapy improves the immunoregulation of autoaggressive T effector cells in MS patients by changing the IL-6 signal transduction pathway, thus restoring their sensitivity to Treg-mediated suppression.

  17. 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.

  18. Immunologische Effekte von Interferon beta und Glatiramerazetat in der Behandlung der Multiplen Sklerose

    Directory of Open Access Journals (Sweden)

    Berger T

    2008-01-01

    Full Text Available Die Multiple Sklerose (MS stellt die häufigste, potentiell behindernde neurologische Erkrankung im jungen Erwachsenenalter dar. Wiederkehrende Krankheitsschübe und/oder schleichende Krankheitsprogression kennzeichnen den klinischen Verlauf. Die histopathologischen Merkmale setzen sich aus einer chronischen Entzündungsreaktion, demyelinisierenden Herden sowie aus axonaler Schädigung im zentralen Nervensystem zusammen. In mehreren Phase-III-Studien wurde belegt, dass durch die Behandlung mit Interferon (IFN β und Glatiramerazetat (GA sowohl eine Reduktion der Schubrate als auch eine Reduktion von Krankheitsaktivitätsmarkern in der Magnetresonanztomografie bei MS erreicht werden kann. IFN β entfaltet seine Wirkung an mehreren Schnittstellen entlang der immunpathogenetischen Kaskade und verringert unter anderem die Aktivierung von autoreaktiven T-Lymphozyten sowie deren Migration durch die Blut-Hirn-Schranke. GA ist durch seine Fähigkeit, GA-spezifische Th2-Lymphozyten zu induzieren, imstande, pro-entzündliche Reaktionen, die durch autoreaktive T-Lymphozyten getriggert werden, in Richtung anti-entzündliche Immunantworten zu modulieren. Anhand der derzeit postulierten pathogenetischen Mechanismen bei MS werden immunologische und Aspekte der sicheren Anwendung beider Therapien besprochen.

  19. Molecular determinants of desensitization and assembly of the chimeric GABA(A) receptor subunits (alpha1/gamma2) and (gamma2/alpha1) in combinations with beta2 and gamma2

    DEFF Research Database (Denmark)

    Elster, L; Kristiansen, U; Pickering, D S;

    2001-01-01

    )beta2gamma2 subunit combinations formed functional receptor complexes as shown by whole-cell patch-clamp recordings and [3H]muscimol and [3H]flunitrazepam binding. Moreover, the surface immunofluorescence staining of Sf-9 cells expressing the (alpha1/gamma2)-containing receptors was pronounced......Two gamma-aminobutyric acid(A) (GABA(A)) receptor chimeras were designed in order to elucidate the structural requirements for GABA(A) receptor desensitization and assembly. The (alpha1/gamma2) and (gamma2/alpha1) chimeric subunits representing the extracellular N-terminal domain of alpha1 or gamma......2 and the remainder of the gamma2 or alpha1 subunits, respectively, were expressed with beta2 and beta2gamma2 in Spodoptera frugiperda (Sf-9) cells using the baculovirus expression system. The (alpha1/gamma2)beta2 and (alpha1/gamma2)beta2gamma2 but not the (gamma2/alpha1)beta2 and (gamma2/alpha1...

  20. Evidence for the virtual beta-gamma transition in 59Ni

    CERN Document Server

    Pfützner, M; Żylicz, J

    2015-01-01

    A novel theory of radiative electron capture in second forbidden non-unique transition, is applied to reanalyze experimental data obtained previously for the decay of 59Ni. The measured gamma spectrum is shown to be distorted at the high-energy end, presenting the first direct evidence for the virtual beta-gamma transition through the excited state in 59Co. The complete theoretical predictions, including both the direct and the virtual decay channels, as well as the interference between them, reproduce very well the experimental spectrum. The virtual nuclear component amounts to about 4% of the total gamma intensity.

  1. Expression of biologically active recombinant equine interferon-gamma by two different baculovirus gene expression systems using insect cells and silkworm larvae.

    Science.gov (United States)

    Wu, Donglai; Murakami, Kenji; Liu, Nihong; Inoshima, Yasuo; Yokoyama, Takashi; Kokuho, Takehiro; Inumaru, Shigeki; Matsumura, Tomio; Kondo, Takashi; Nakano, Katsushige; Sentsui, Hiroshi

    2002-10-21

    The full-length equine interferon-gamma (eIFN-gamma) cDNA, including the secretion signal peptide coding region, was recloned into baculovirus transfer vector pAcYM1. This vector was co-transfected with Autographa californica nuclear polyhedrosis virus DNA or hybrid nuclear polyhedrosis virus DNA into Spodoptera frugiperda cells. The recombinant viruses, named AcEIFN-gamma and HyEIFN-gamma, were then recovered. Recombinant eIFN-gamma (reIFN-gamma) was accumulated in the culture fluid of the AcEIFN-gamma or HyEIFN-gamma infected Tricoplusia ni -derived cell line, BTI TN 5B1-4, and hemolymph of HyEIFN-gamma infected silkworm larvae. These reIFN-gamma forms were shown to be 14, 16, 18 and 20kDa proteins, and glycosylated as confirmed by SDS-PAGE and tunicamycin treatment. Both reIFN-gamma proteins, showed high-level biological activities to vesicular stomatitis virus by cytopathic effect reduction assay, and MHC class II antigen induction on the equine fetal kidney-78 cell line. PMID:12445800

  2. 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.

  3. 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.

  4. Weighted $\\beta\\gamma$-summability of fuzzy functions of order $\\theta$

    OpenAIRE

    Ojha, Sarita; Srivastava, P. D.

    2016-01-01

    The concept of weighted $\\beta\\gamma$ - summability of order $\\theta$ in case of fuzzy functions is introduced and classified into ordinary and absolute sense. Several inclusion relations among the sets are investigated. Also we have found some suitable conditions to get its relation with the generalized statistical convergence. Finally we have proved a generalized version of Tauberian theorem.

  5. Generalized Bessel transform of $(\\beta, \\gamma)$-generalized Bessel Lipschitz functions

    OpenAIRE

    DAHER, Radouan; El Hamma, Mohamed

    2015-01-01

    In this paper, we prove an analog of Younis’s theorem 5.2 in~[4] for the generalized Fourier-Bessel transform on the Half line for functions satisfying the $(\\beta, \\gamma)$-generalized Bessel Lipschitz condition in the space $\\mathrm{L}^{2}_{\\alpha,n}$.

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

    International Nuclear Information System (INIS)

    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)

  7. Homology modeling of human alpha 1 beta 2 gamma 2 and house fly beta 3 GABA receptor channels and Surflex-docking of fipronil.

    Science.gov (United States)

    Cheng, Jin; Ju, Xiu-Lian; Chen, Xiang-Yang; Liu, Gen-Yan

    2009-09-01

    To further explore the mechanism of selective binding of the representative gamma-aminobutyric acid receptors (GABARs) noncompetitive antagonist (NCA) fipronil to insect over mammalian GABARs, three-dimensional models of human alpha 1 beta 2 gamma 2 and house fly beta 3 GABAR were generated by homology modeling, using the cryo-electron microscopy structure of the nicotinic acetylcholine receptor (nAChR) of Torpedo marmorata as a template. Fipronil was docked into the putative binding site of the human alpha 1 beta 2 gamma 2 and house fly beta 3 receptors by Surflex-docking, and the calculated docking energies are in agreement with experimental results. The GABA receptor antagonist fipronil exhibited higher potency with house fly beta 3 GABAR than with human alpha 1 beta 2 gamma 2 GABAR. Furthermore, analyses of Surflex-docking suggest that the H-bond interaction of fipronil with Ala2 and Thr6 in the second transmembrane segment (TM2) of these GABARs plays a relatively important role in ligand selective binding. The different subunit assemblies of human alpha 1 beta 2 gamma 2 and house fly beta 3 GABARs may result in differential selectivity for fipronil.

  8. In-vitro Quantitative Assay of Interferon Gamma in Serum of Nigerian Indigenous and Exotic Breeds of Chickens

    Directory of Open Access Journals (Sweden)

    Esan Oluwaseun and Oladele Omolade

    2014-12-01

    Full Text Available The Nigerian Indigenous breeds of Chicken (NIC have thrived in harsh tropical environment with little veterinary care and poor nutrition compared with the introduced exotic breeds which performs sub-optimally in the tropics. However, they receive little attention for commercial production in spite of low input required. A comparative assessment of cellular immune response of the indigenous and exotic breeds was carried out to provide scientific explanation for their hardy nature and justify production for economic purposes. Fifteen chickens from each of three indigenous breeds i.e. Frizzled- feathered, Naked-neck and Smooth-feathered, and 8 Isa Brown pullets were 10 weeks old and reared in separate cages. The chickens were stabilized and administered Newcastle Disease Vaccine (NDV, LaSota strain. At 14 and 16 weeks old, all breeds were administered NDV Komarov strain in Freund’s adjuvant and in PBS intramuscularly as sensitizing and challenge inoculants, respectively. They were bled for serum 5 days later and concentrations of Interferon-gamma (IFN-gamma were determined using competitive Enzyme-linked immunosorbent assay. Results showed that the Frizzled-feathered chickens had the highest concentration of IFN-gamma (58±2.8 pg/ml which was significantly higher than 49±3.2 pg/ml and 44±2.5 pg/ml recorded for Smooth-feathered and Isa brown breeds respectively. Also, concentration in Naked-neck breed was 54±2.9 pg/ml, which was significantly higher than Isa Brown. Isa Brown had the significantly lowest concentration. It was concluded that the three NIC studied, have inherent capacity to mount higher levels of cellular immune response compared with the exotic Isa brown, when challenged.

  9. Interferon-beta induces distinct gene expression response patterns in human monocytes versus T cells.

    Directory of Open Access Journals (Sweden)

    Noa Henig

    Full Text Available BACKGROUND: Monocytes, which are key players in innate immunity, are outnumbered by neutrophils and lymphocytes among peripheral white blood cells. The cytokine interferon-β (IFN-β is widely used as an immunomodulatory drug for multiple sclerosis and its functional pathways in peripheral blood mononuclear cells (PBMCs have been previously described. The aim of the present study was to identify novel, cell-specific IFN-β functions and pathways in tumor necrosis factor (TNF-α-activated monocytes that may have been missed in studies using PBMCs. METHODOLOGY/PRINCIPAL FINDINGS: Whole genome gene expression profiles of human monocytes and T cells were compared following in vitro priming to TNF-α and overnight exposure to IFN-β. Statistical analyses of the gene expression data revealed a cell-type-specific change of 699 transcripts, 667 monocyte-specific transcripts, 21 T cell-specific transcripts and 11 transcripts with either a difference in the response direction or a difference in the magnitude of response. RT-PCR revealed a set of differentially expressed genes (DEGs, exhibiting responses to IFN-β that are modulated by TNF-α in monocytes, such as RIPK2 and CD83, but not in T cells or PBMCs. Known IFN-β promoter response elements, such as ISRE, were enriched in T cell DEGs but not in monocyte DEGs. The overall directionality of the gene expression regulation by IFN-β was different in T cells and monocytes, with up-regulation more prevalent in T cells, and a similar extent of up and down-regulation recorded in monocytes. CONCLUSIONS: By focusing on the response of distinct cell types and by evaluating the combined effects of two cytokines with pro and anti-inflammatory activities, we were able to present two new findings First, new IFN-β response pathways and genes, some of which were monocytes specific; second, a cell-specific modulation of the IFN-β response transcriptome by TNF-α.

  10. Gamma interferon (IFN-γ) receptor restricts systemic dengue virus replication and prevents paralysis in IFN-α/β receptor-deficient mice.

    Science.gov (United States)

    Prestwood, Tyler R; Morar, Malika M; Zellweger, Raphaël M; Miller, Robyn; May, Monica M; Yauch, Lauren E; Lada, Steven M; Shresta, Sujan

    2012-12-01

    We previously reported that mice lacking alpha/beta and gamma interferon receptors (IFN-α/βR and -γR) uniformly exhibit paralysis following infection with the dengue virus (DENV) clinical isolate PL046, while only a subset of mice lacking the IFN-γR alone and virtually no mice lacking the IFN-α/βR alone develop paralysis. Here, using a mouse-passaged variant of PL046, strain S221, we show that in the absence of the IFN-α/βR, signaling through the IFN-γR confers approximately 140-fold greater resistance against systemic vascular leakage-associated dengue disease and virtually complete protection from dengue-induced paralysis. Viral replication in the spleen was assessed by immunohistochemistry and flow cytometry, which revealed a reduction in the number of infected cells due to IFN-γR signaling by 2 days after infection, coincident with elevated levels of IFN-γ in the spleen and serum. By 4 days after infection, IFN-γR signaling was found to restrict DENV replication systemically. Clearance of DENV, on the other hand, occurred in the absence of IFN-γR, except in the central nervous system (CNS) (brain and spinal cord), where clearance relied on IFN-γ from CD8(+) T cells. These results demonstrate the roles of IFN-γR signaling in protection from initial systemic and subsequent CNS disease following DENV infection and demonstrate the importance of CD8(+) T cells in preventing DENV-induced CNS disease. PMID:22973027

  11. Organization of human interferon gamma-heparin complexes from solution properties and hydrodynamics.

    Science.gov (United States)

    Perez Sanchez, Horacio; Tatarenko, Karine; Nigen, Michael; Pavlov, Georges; Imberty, Anne; Lortat-Jacob, Hugues; Garcia de la Torre, Jose; Ebel, Christine

    2006-11-01

    Heparan sulfate (HS) recognizes a variety of proteins, one of which is the pleiotropic cytokine IFN-gamma, and as such modulates many biological processes. IFN-gamma is a homodimer with a well-defined core and two flexible C-termini that constitute HS binding domains. We show here using molecular modeling that an extended IFN-gamma structure overlaps a HS fragment of 16 disaccharides (16 nm). Since a 21-24-disaccharide HS fragment was experimentally defined as the minimum size that interacts with IFN-gamma [Lortat-Jacob, H., Turnbull, J. E., and Grimaud, J. A. (1995) Biochem. J. 310 (Part 2), 497-505], this raises the question of the complexe organization. We combine analytical ultracentrifugation, size exclusion chromatography, and hydrodynamic bead modeling to characterize the complexes formed in solution with heparin oligosaccharides. For oligosaccharides of 14 and 20 nm, two types of complexes are formed with one IFN-gamma and one or two heparin molecules. Complexes consisting of two IFN-gamma and one or two heparin molecules are present for a fragment of 25 nm and aggregates for a fragment of 35 nm. The complexes are rather compact and can be formed without major conformational changes of the partners. The complex pattern of interaction is related to the size of the partners and their multiple binding possibilities. These various possibilities suggest networks of interactions at the crowded surface of the cells. Hydrodynamic methods used here proved to be very efficient tools for describing protein-HS complexes that, due to the intrinsic heterogeneity and flexibility of the partners, are otherwise very difficult to analyze.

  12. Production of biologically active recombinant bovine interferon-gamma by two different baculovirus gene expression systems using insect cells and silkworm larvae.

    Science.gov (United States)

    Murakami, K; Uchiyama, A; Kokuho, T; Mori, Y; Sentsui, H; Yada, T; Tanigawa, M; Kuwano, A; Nagaya, H; Ishiyama, S; Kaki, H; Yokomizo, Y; Inumaru, S

    2001-01-01

    The full-length bovine interferon-gamma (bIFN-gamma) cDNA, including the secretion signal peptide coding region was recloned into baculovirus transfer vectors pAcYM1 and pBm050. These vectors were co-transfected with Autographa californica nuclear polyhedrosis virus (AcNPV) or Bombyx mori nuclear polyhedrosis virus (BmNPV) DNA into Spodoptera frugiperda cells (SF21AE) and Bombyx mori cells (BmN), respectively. The recombinant viruses, named AcBIFN-gamma and BmBIFN-gamma, were then recovered. Recombinant bIFN-gamma (rbIFN-gamma) was accumulated in the culture fluid of AcBIFN-gamma-infected Trichoplusia ni cells and BmBIFN-gamma-infected silkworm larvae. These rbIFN-gamma forms were shown to be glycosylated 20 and 22 kDa proteins as confirmed by SDS-PAGE and tunicamycin treatment. These products were sensitive to cystein proteinase. Both rbIFN-gamma proteins, showed high-level biological activities by plaque reduction assay using vesicular stomatitis virus, and MHC class II antigen induction on bovine macrophage cells. PMID:11145838

  13. Counting efficiency for radionuclides decaying by beta and gamma-ray emission

    International Nuclear Information System (INIS)

    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: 20O, 20F, 28Al, 35P,41Ar, 42K, 47Se, 62Fe, 66Cu, 81Ge, 86Rb, 104Rh, 108Ru, 112Pd, 121Sn(m), 122In, 129I, 141Ce, 142Pr, 151Sm, 170Tm, 171Tm, 194Os, 203Hg, 205Hg, 210Pb, 225Ra, 244Am(m). It has been assumed that the liquid is a toluene based scintillator solution in standard glass vials containing 10 cm3. (Author)

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

    International Nuclear Information System (INIS)

    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

  15. Release of tumor necrosis factor, interleukin-2, and gamma-interferon in serum after injection of OKT3 monoclonal antibody in kidney transplant recipients.

    Science.gov (United States)

    Abramowicz, D; Schandene, L; Goldman, M; Crusiaux, A; Vereerstraeten, P; De Pauw, L; Wybran, J; Kinnaert, P; Dupont, E; Toussaint, C

    1989-04-01

    High levels of tumor necrosis factor-alpha, interleukin-2, and gamma-interferon appeared in the circulation of kidney transplant recipients after the first injection of the monoclonal antibody OKT3. This initial injection was systematically followed by fever. The three cytokines were released in all patients (n = 9), with peak serum levels of tumor necrosis factor occurring 1 hr after OKT3 injection and those of interleukin-2 and gamma-interferon after 2 hr. Cytokines were not released after the second and third OKT3 injections, when CD3+ cells had disappeared from blood. These findings suggest that circulating cytokines are released by T cells after activation by OKT3. These cytokines are probably involved in the systematic reactions observed after injection of OKT3. PMID:2523100

  16. Analysis of the interferon gamma (rs2430561, +874T/A) functional gene variant in relation to the presence of cardiovascular events in rheumatoid arthritis

    OpenAIRE

    Mercedes García-Bermúdez; Raquel López-Mejías; Carlos González-Juanatey; Alfonso Corrales; Gema Robledo; Santos Castañeda; Miranda-Filloy, José A.; Ricardo Blanco; Benjamín Fernández-Gutiérrez; Alejandro Balsa; Isidoro González-Alvaro; Carmen Gómez-Vaquero; Javier Llorca; Javier Martín; Miguel A. González-Gay

    2012-01-01

    Objective: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) morbidity and mortality. Since interferon-gamma (IFN-γ) has a direct effect on inflammation, in this study we assessed the potential association of the IFNG functional gene variant rs2430561 with CV disease in patients with RA. Methods: One thousand six hundred and thirty-five patients fulfilling the 1987 American College of Rheumatology classification criteria for RA were geno...

  17. Follow-Up Study of Tuberculosis-Exposed Supermarket Customers with Negative Tuberculin Skin Test Results in Association with Positive Gamma Interferon Release Assay Results▿

    Science.gov (United States)

    Franken, Willeke P. J.; Koster, Ben F. P. J.; Bossink, Ailko W. J.; Thijsen, Steven F. T.; Bouwman, John J. M.; van Dissel, Jaap T.; Arend, Sandra M.

    2007-01-01

    We report a follow-up study of 29 subjects with negative tuberculin skin test (TST) results in association with positive gamma interferon release assay (IGRA) results, mainly due to responses to CFP-10 in the T-SPOT.TB assay, during a contact investigation. One year later, 12/29 subjects (41%) had converted to positive TST results in association with negative IGRA results. PMID:17626157

  18. Route of Infection That Induces a High Intensity of Gamma Interferon-Secreting T Cells in the Genital Tract Produces Optimal Protection against Chlamydia trachomatis Infection in Mice

    OpenAIRE

    Igietseme, Joseph U.; Uriri, Ijindah M.; Kumar, Shantha N.; Ananaba, Godwin A.; Ojior, Omegbhai O.; Momodu, Inua A.; Candal, Debra H.; Black, Carolyn M.

    1998-01-01

    The induction of local T helper type 1 (Th1)-mediated cellular immunity is crucial for resistance of mice to genital infection by the obligate intracellular bacterium Chlamydia trachomatis. We tested the hypothesis that the route of immunization that elicits relatively high numbers of chlamydia-specific, gamma interferon (IFN-γ)-secreting T lymphocytes (ISTLs) in the genital tract would induce optimal protective immunity against reinfection. Female BALB/c mice were infected intravaginally (i....

  19. Development and Evaluation of a Real-Time Reverse Transcription-PCR Assay for Quantification of Gamma Interferon mRNA To Diagnose Tuberculosis in Multiple Animal Species▿

    OpenAIRE

    Harrington, Noel P.; Surujballi, Om P.; Waters, W. Ray; Prescott, John F.

    2007-01-01

    Tuberculosis of free-ranging and captive wildlife, including species implicated in the maintenance and transmission of Mycobacterium bovis, is a difficult disease to diagnose and control. Historically, diagnosis of tuberculosis has relied largely upon assays of cell-mediated immunity (CMI), such as tuberculin skin testing. This approach, however, is problematic or impractical for use with many wildlife species. Increasingly, in vitro diagnostic tests, including gamma interferon (IFN-γ)-based ...

  20. Azathioprine versus beta interferons for relapsing-remitting multiple sclerosis: a multicentre randomized non-inferiority trial.

    Directory of Open Access Journals (Sweden)

    Luca Massacesi

    Full Text Available 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 β interferons for

  1. 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

  2. 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

    beta-1b 250 microg (n=292; early treatment) or placebo (n=176; delayed treatment) subcutaneously every other day for 2 years, or until diagnosis of CDMS. All patients were then eligible to enter a prospectively planned follow-up phase with open-label interferon beta-1b up to a maximum of 5 years after...

  3. Interferon Beta-1a (AVONEX® as a Treatment Option for Untreated Patients with Multiple Sclerosis (AXIOM: A Prospective, Observational Study

    Directory of Open Access Journals (Sweden)

    Christoph Kleinschnitz

    2015-07-01

    Full Text Available The efficacy and safety of first-line disease-modifying therapies (DMT for relapsing-remitting multiple sclerosis (RRMS has been demonstrated in pivotal, randomized trials, but these studies do not reflect the routine care setting where treatment gaps or switches are common. The Avonex as Treatment Option for Untreated MS Patients (AXIOM trial assessed the efficacy of newly-initiated intramuscular interferon beta-1a (IM IFNb-1a after a treatment-free interval, with particular consideration of the previous course of disease and therapy. The AXIOM trial was an open, 12-month, observational, non-interventional study with a retrospective and a prospective part conducted in Germany. RRMS patients with a treatment-free interval of at least three months were included and treated with IFNb-1a for up to 12 months. Relapse rate, disability progression, injection-related parameters and quality of life observed during the prospective part were compared with retrospectively-collected data. Two hundred and thirty five RRMS patients participated in AXIOM. The mean relapse rate decreased from 1.1 in the three months before baseline to 0.2 per quarter during the twelve-month observational period; the Multiple Sclerosis Functional Composite score improved during twelve months of IM IFNb-1a treatment, while the Expanded Disability Status Scale score did not change over the course of this study. Compared to previous DMTs (IM IFNb-1a, subcutaneous IFNb-1a (SC IFNb-1a, SC IFNb-1b, glatiramer acetate, the patients experienced less injection site reactions and flu-like symptoms, with a stated improved quality of life. IM IFNb-1a was effective and well accepted in RRMS patients with no or discontinued previous therapy. These results from the routine care setting may inform optimization of DMT treatment in RRMS, but need confirmation in further studies.

  4. Atorvastatin added to interferon beta for relapsing multiple sclerosis: 12-month treatment extension of the randomized multicenter SWABIMS trial.

    Directory of Open Access Journals (Sweden)

    Christian P Kamm

    Full Text Available BACKGROUND: Statins have anti-inflammatory and immunomodulatory properties in addition to lipid-lowering effects. OBJECTIVES: To report the 12-month extension of a phase II trial evaluating the efficacy, safety and tolerability of atorvastatin 40 mg/d added to interferon beta-1b (IFNB-1b in relapsing-remitting multiple sclerosis (RRMS. METHODS: In the randomized, multicenter, parallel-group, rater-blinded core study, 77 RRMS patients started IFNB-1b. At month three they were randomized 1∶1 to receive atorvastatin 40 mg/d or not in addition to IFNB-1b until month 15. In the subsequent extension study, patients continued with unchanged medication for another 12 months. Data at study end were compared to data at month three of the core study. RESULTS: 27 of 72 patients that finished the core study entered the extension study. 45 patients were lost mainly due to a safety analysis during the core study including a recruitment stop for the extension study. The primary end point, the proportion of patients with new lesions on T2-weighted images was equal in both groups (odds ratio 1.926; 95% CI 0.265-14.0007; p = 0.51. All secondary endpoints including number of new lesions and total lesion volume on T2-weighted images, total number of Gd-enhancing lesions on T1-weighted images, volume of grey and white matter, EDSS, MSFC, relapse rate, number of relapse-free patients and neutralizing antibodies did not show significant differences either. The combination therapy was well tolerated. CONCLUSIONS: Atorvastatin 40 mg/day in addition to IFNB-1b did not have any beneficial effects on RRMS compared to IFNB-1b monotherapy over a period of 24 months. TRIAL REGISTRATION: ClinicalTrials.gov NCT01111656.

  5. [Interferon alpha antibodies show no cross reactions with typical autoantibodies].

    Science.gov (United States)

    Görg, S; Klouche, M; Wilhelm, D; Kirchner, H

    1993-04-01

    Patients treated with natural human interferon alpha develop anti-interferon antibodies (IFN-AB) only in very rare cases. By contrast, patients with autoimmune disorders are able to generate high-titered IFN-AB against endogenous interferon alpha. One explanation for the development of auto-IFN-AB could be cross-reactivity with typical autoimmune antigens. We investigated the cross-reactivity of 3 high-titered IgG IFN-AB of female autoimmune patients (aged 32, 36, 74 years; two severe cases of SLE, one case of autoimmune thyroiditis) as well as 25 low-titered natural IgM IFN-AB of healthy blood donors (aged 19-48 years). Typical autoimmune antigens including dsDNA, ENA, as well as natural interferon beta and recombinant interferon gamma are not able to inhibit binding of IFN-AB to interferon alpha in an ELISA test system. Preincubation of sera containing either dsDNA antibodies (dsDNA-AB) (24 patients), thyroid peroxidase (TPO-AB) (9 patients) or thyroglobulin (TG-AB) (12 patients) with interferon alpha resulted in no change in the respective autoantibody titer. These data suggest that there is no cross-reactivity between IFN-alpha-AB and dsDNA-AB, TPO-AB or TG-AB. Thus, an explanation for the occurrence of IFN-AB in autoimmune disorders cannot be found in a cross-reaction between interferon alpha with typical autoimmune antigens.

  6. Diagnosis of latent tuberculosis infection among HIV discordant partners using interferon gamma release assays

    Directory of Open Access Journals (Sweden)

    Mwananyanda Lawrence

    2011-09-01

    Full Text Available Abstract Background There is limited data on the effect of HIV status and CD4 counts on performance of Interferon-g Release assays (IGRAs for diagnosis of latent tuberculosis infection (LTBI. Methods A cross sectional study was conducted to assess the prevalence of and risk factors for a positive diagnostic test for LTBI, using tuberculin skin test (TST and IGRAs among HIV-discordant couples in Zambia. Results A total of 596 subjects (298 couples were enrolled. Median CD4 count among HIV positive persons was 388 cells/μl, (range 51-1330. HIV negative persons were more likely than their HIV positive partner, to have a positive diagnostic test for LTBI with TST (203 vs 128, QFT (171 vs 109 and TSPOT (156 vs. 109. On multivariate analysis, HIV negative status was an independent predictor for a positive QFT (OR = 2.22, 95% CI 1.42- 3.46 and TSPOT (OR = 1.79, 95% CI 1.16-2.77. Among HIV positive subjects a CD4 count ≥ 388 cells/μl was associated with a positive TST (OR = 1.76 95% CI 1.10-2.82 and QFT (OR = 1.71 95% CI 1.06-2.77 but not TSPOT (OR = 1.20 95% CI 0.74-1.94. Conclusions Persons with HIV had significantly fewer positive diagnostic tests for LTBI with TST, QFT and TSPOT. Persons with a CD4 count

  7. First identification of. gamma. rays in the. beta. /sup +//EC decay of sup(104,105)Sn

    Energy Technology Data Exchange (ETDEWEB)

    Deneffe, K.; Coenen, E.; Huyse, M.; Duppen, P. van (LISOL, Leuven (Belgium). Inst. voor Kern- en Stralingsfysika); Vanhorenbeeck, J. (Universite Libre de Bruxelles (Belgium)); Marmol, P. del; Fettweis, P. (Centre d' Etude de l' Energie Nucleaire, Mol (Belgium))

    1985-03-01

    The ..beta../sup +//EC decay of mass-separated /sup 104/Sn and /sup 105/Sn isotopes was studied by x-ray and ..gamma..-ray singles, as well as by x-..gamma.. and ..gamma..-..gamma.. coincidences. Sources were produced in the reactions /sup 92/Mo (/sup 20/Ne, ypxn). The nucleus /sub 50//sup 104/Sn with Tsub(1/2 = 23 +- 2 s was identified. A partial decay scheme of /sup 105/Sn is proposed.

  8. 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.

  9. The Protozoan Neospora caninum Directly Triggers Bovine NK Cells To Produce Gamma Interferon and To Kill Infected Fibroblasts

    Science.gov (United States)

    Boysen, Preben; Klevar, Siv; Olsen, Ingrid; Storset, Anne K.

    2006-01-01

    Natural killer (NK) cells are considered to be key players in the early innate responses to protozoan infections, primarily indirectly by producing gamma interferon (IFN-γ) in response to cytokines, like interleukin 12 (IL-12). We demonstrate that live, as well as heat-inactivated, tachyzoites of Neospora caninum, a Toxoplasma-like protozoan, directly trigger production of IFN-γ from purified, IL-2-activated bovine NK cells. This response occurred independently of IL-12 but was increased by the addition of the cytokine. A similar IFN-γ response was measured in cocultures of NK cells and N. caninum-infected autologous fibroblasts. However, no NK cell-derived IFN-γ response was detected when cells were cultured with soluble antigens from the organism, indicating that intact tachyzoites or nonsoluble components are necessary for NK cell triggering. Furthermore, N. caninum-infected autologous fibroblasts had increased susceptibility to NK cell cytotoxicity compared to uninfected fibroblasts. This cytotoxicity was largely mediated by a perforin-mediated mechanism. The activating receptor NKp46 was involved in cytotoxicity against fibroblasts but could not explain the increased cytotoxicity against infected targets. Interestingly, N. caninum tachyzoites were able to infect cultured NK cells, in which tachyzoites proliferated inside parasitophorous vacuoles. Together, these findings underscore the role of NK cells as primary responders during a protozoan infection, describe intracellular protozoan infection of NK cells in vitro for the first time, and represent the first functional study of purified bovine NK cells in response to infection. PMID:16428740

  10. Interferon-gamma produced by microglia and the neuropeptide PACAP have opposite effects on the viability of neural progenitor cells.

    Science.gov (United States)

    Mäkelä, Johanna; Koivuniemi, Raili; Korhonen, Laura; Lindholm, Dan

    2010-01-01

    Inflammation is part of many neurological disorders and immune reactions may influence neuronal progenitor cells (NPCs) contributing to the disease process. Our knowledge about the interplay between different cell types in brain inflammation are not fully understood. It is important to know the mechanisms and factors involved in order to enhance regeneration and brain repair. We show here that NPCs express receptors for interferon-gamma (IFNgamma), and IFNgamma activates the signal transducer and activator of transcription (STAT) protein-1. IFNgamma reduced cell proliferation in NPCs by upregulation of the cell cycle protein p21 as well as induced cell death of NPCs by activating caspase-3. Studies of putative factors for rescue showed that the neuropeptide, Pituitary adenylate cyclase-activating polypeptide (PACAP) increased cell viability, the levels of p-Bad and reduced caspase-3 activation in the NPCs. Medium from cultured microglia contained IFNgamma and decreased the viability of NPCs, whilst blocking with anti-IFNgamma antibodies counteracted this effect. The results show that NPCs are negatively influenced by IFNgamma whereas PACAP is able to modulate its action. The interplay between IFNgamma released from immune cells and PACAP is of importance in brain inflammation and may affect the regeneration and recruitment of NPCs in immune diseases. The observed effects of IFNgamma on NPCs deserve to be taken into account in human anti-viral therapies particularly in children with higher rates of brain stem cell proliferation.

  11. Clinical and bacteriological correlates of whole blood interferon gamma (IFN-γ) in newly detected cases of pulmonary TB

    Institute of Scientific and Technical Information of China (English)

    Bandyopadhyay M; Bhakta A; Chakrabarty S; Pal M; Bharati P

    2010-01-01

    Objective:To determine the relationship of the capacity to produce interferon gamma (IFN-毭) in whole blood, bacteriological, hematological, radiographic and clinical presentations in new,HIVseronegative cases of pulmonary tuberculosis (TB).Methods: 80 cases and 50 control subjects aged 15 years onwards, representative of Kasturba Hospital and Nursing schools of Wardha district of Maharashtra state in India were examined for their health condition with standard methodology.Results: Among theseTB patients, 73.8% were Quantiferon-TB gold (QFT) positive withIFN-γ concentration as 0.35 IU or more and there was none in healthy controls. The meanIFN-γ concentrations varied between 9.58IU (50-59 yrs) and 2.58IU ≥60 yrs), showing no trend. The differences in positivity and meanIFN-γconcentrations were statistically insignificant. Both the QFT positivity andIFN-γconcentrations were higher in normal lymphocyte percent as compared to below and above normal, but differences were not statistically significant.Conclusions: TheIFN-γconcentrations are not correlated with any of the predictors of disease severity studied, the levels are significantly higher in observation group as compared to healthy group.

  12. 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.

  13. Mycobacterium tuberculosis induces interleukin-32 production through a caspase- 1/IL-18/interferon-gamma-dependent mechanism.

    Directory of Open Access Journals (Sweden)

    Mihai G Netea

    2006-08-01

    Full Text Available BACKGROUND: Interleukin (IL-32 is a newly described proinflammatory cytokine that seems likely to play a role in inflammation and host defense. Little is known about the regulation of IL-32 production by primary cells of the immune system. METHODS AND FINDINGS: In the present study, freshly obtained human peripheral blood mononuclear cells were stimulated with different Toll-like receptor (TLR agonists, and gene expression and synthesis of IL-32 was determined. We demonstrate that the TLR4 agonist lipopolysaccharide induces moderate (4-fold production of IL-32, whereas agonists of TLR2, TLR3, TLR5, or TLR9, each of which strongly induced tumor necrosis factor alpha and IL-6, did not stimulate IL-32 production. However, the greatest amount of IL-32 was induced by the mycobacteria Mycobacterium tuberculosis and M. bovis BCG (20-fold over unstimulated cells. IL-32-induced synthesis by either lipopolysaccharide or mycobacteria remains entirely cell-associated in monocytes; moreover, steady-state mRNA levels are present in unstimulated monocytes without translation into IL-32 protein, similar to other cytokines lacking a signal peptide. IL-32 production induced by M. tuberculosis is dependent on endogenous interferon-gamma (IFNgamma; endogenous IFNgamma is, in turn, dependent on M. tuberculosis-induced IL-18 via caspase-1. CONCLUSIONS: In conclusion, IL-32 is a cell-associated proinflammatory cytokine, which is specifically stimulated by mycobacteria through a caspase-1- and IL-18-dependent production of IFNgamma.

  14. Interferon-gamma produced by microglia and the neuropeptide PACAP have opposite effects on the viability of neural progenitor cells.

    Directory of Open Access Journals (Sweden)

    Johanna Mäkelä

    Full Text Available Inflammation is part of many neurological disorders and immune reactions may influence neuronal progenitor cells (NPCs contributing to the disease process. Our knowledge about the interplay between different cell types in brain inflammation are not fully understood. It is important to know the mechanisms and factors involved in order to enhance regeneration and brain repair. We show here that NPCs express receptors for interferon-gamma (IFNgamma, and IFNgamma activates the signal transducer and activator of transcription (STAT protein-1. IFNgamma reduced cell proliferation in NPCs by upregulation of the cell cycle protein p21 as well as induced cell death of NPCs by activating caspase-3. Studies of putative factors for rescue showed that the neuropeptide, Pituitary adenylate cyclase-activating polypeptide (PACAP increased cell viability, the levels of p-Bad and reduced caspase-3 activation in the NPCs. Medium from cultured microglia contained IFNgamma and decreased the viability of NPCs, whilst blocking with anti-IFNgamma antibodies counteracted this effect. The results show that NPCs are negatively influenced by IFNgamma whereas PACAP is able to modulate its action. The interplay between IFNgamma released from immune cells and PACAP is of importance in brain inflammation and may affect the regeneration and recruitment of NPCs in immune diseases. The observed effects of IFNgamma on NPCs deserve to be taken into account in human anti-viral therapies particularly in children with higher rates of brain stem cell proliferation.

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

    International Nuclear Information System (INIS)

    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)

  16. Cost-effectiveness analysis of peginterferon beta-1a compared with interferon beta-1a and glatiramer acetate in the treatment of relapsing-remitting multiple sclerosis in the United States.

    Science.gov (United States)

    Hernandez, Luis; Guo, Shien; Kinter, Elizabeth; Fay, Monica

    2016-07-01

    Objective Peginterferon beta-1a 125 mcg, administered subcutaneously (SC) every 2 weeks, a new disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS), was approved by the US Food and Drug Administration in 2014. This study assesses the cost-effectiveness of peginterferon beta-1a vs interferon beta-1a (44 mcg SC 3 times per week) and glatiramer acetate (20 mg SC once-daily) in the treatment of RRMS from the perspective of a US payer over 10 years. Methods A Markov cohort economic model was developed for this analysis. The model predicts disability progression, occurrence of relapses and other adverse events and translates them into quality-adjusted life years (QALYs) and costs. Natural history data were obtained from the placebo arm of the ADVANCE trial of peginterferon beta-1a, the London Ontario (Canada) database and a large population-based MS survey. Comparative efficacy of each DMT vs placebo was obtained from a network meta-analysis. Costs (in 2014 US dollars) were sourced from public databases and literature. Clinical and economic outcomes were discounted at 3% per year. Results Over 10 years, peginterferon beta-1a was dominant (i.e., more effective and less costly), with cost-savings of $22,070 and additional 0.06 QALYs when compared with interferon beta-1a 44 mcg and with cost-savings of $19,163 and 0.07 QALYs gained when compared with glatiramer acetate 20 mg. Results were most sensitive to variations in the treatment effect of each DMT, treatment acquisition costs of each DMT and the time horizon. Probabilistic sensitivity analyses indicated that peginterferon beta-1a remains dominant in >90% of 5,000 replications compared with either DMTs. Conclusion This analysis suggests that long-term treatment with peginterferon beta-1a improves clinical outcomes at reduced costs compared with interferon beta-1a 44 mcg and glatiramer acetate 20 mg and should be a valuable addition to managed care formularies for treating

  17. Search for double beta decay of $^{136}$Ce and $^{138}$Ce with HPGe gamma detector

    CERN Document Server

    Belli, P; Boiko, R S; Cappella, F; Cerulli, R; Danevich, F A; Incicchitti, A; Kropivyansky, B N; Laubenstein, M; Poda, D V; Polischuk, O G; Tretyak, V I

    2014-01-01

    Search for double $\\beta$ decay of $^{136}$Ce and $^{138}$Ce was realized with 732 g of deeply purified cerium oxide sample measured over 1900 h with the help of an ultra-low background HPGe $\\gamma$ detector with a volume of 465 cm$^3$ at the STELLA facility of the Gran Sasso National Laboratories of the INFN (Italy). New improved half-life limits on double beta processes in the cerium isotopes were set at the level of $\\lim T_{1/2}\\sim 10^{17}-10^{18}$~yr; many of them are even two orders of magnitude larger than the best previous results.

  18. Neutrophil-to-Lymphocyte Ratio Is Associated with Impaired Interferon-Gamma Release to Phytohemagglutinin.

    Directory of Open Access Journals (Sweden)

    Kwang-Sook Woo

    Full Text Available The neutrophil-to-lymphocyte ratio (NLR has been shown to predict adverse outcomes in several pathologic conditions. The majority of indeterminate interferon (IFN-γ release assays were due to inadequate IFN-γ response to the phytohemagglutinin. We sought to study the value of NLR to predict an indeterminate result of QuantiFERON-TB Gold In-Tube (QFT-GIT performed in routine laboratory practice.Results from 2,773 QFT-GIT assays were analyzed. Data collection included demographic data, the level of IFN-γ to nil, mitogen, and TB antigen of QFT-GIT, total WBC, and a differential count. We calculated the absolute neutrophil count, lymphocyte count, and NLR.Of the total, 224 (8.1% indeterminate results were observed. Twelve (1.8% showed indeterminate results in the NLR range from 1.71 to 2.84, but 132 (19.2% had indeterminate results in NLR ≥ 5.18 (p < 0.0001. The likelihood ratio for indeterminate results were 2.70 (95% CI, 2.36-3.08 in NLR ≥ 5.18 and 1.93 (95% CI, 1.64-2.27 in lymphocyte count ≤ 1050/μL. NLR and neutrophil count were independent predictors for indeterminate QFT-GIT result in multiple regression analysis. The IFN-γ response to PHA was negatively associated with NLR (r = -0.33, p < 0.001.We showed that the NLR is an independent predictor of indeterminate QFT-GIT result. Low frequency of indeterminate results in group with normal NLR may imply the importance of a balance between two cellular compartments in physiological and pathological conditions.

  19. Interferon-Gamma-Induced Nitric Oxide Inhibits the Proliferation of Murine Renal Cell Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    David J. Tate Jr., John R. Patterson, Cruz Velasco-Gonzalez, Emily N. Carroll, Janie Trinh, Daniel Edwards, Ashok Aiyar, Beatriz Finkel-Jimenez, Arnold H. Zea

    2012-01-01

    Full Text Available Renal cell carcinoma (RCC remains one of the most resistant tumors to systemic chemotherapy, radiotherapy, and immunotherapy. Despite great progress in understanding the basic biology of RCC, the rate of responses in animal models and clinical trials using interferons (IFNs has not improved significantly. It is likely that the lack of responses can be due to the tumor's ability to develop tumor escape strategies. Currently, the use of targeted therapies has improved the clinical outcomes of patients with RCC and is associated with an increase of Th1-cytokine responses (IFNγ, indicating the importance of IFNγ in inhibiting tumor proliferation. Thus, the present study was designed to investigate a new mechanism by which IFNγ mediates direct anti-proliferative effects against murine renal cell carcinoma cell lines. When cultured RCC cell lines were exposed to murine recombinant IFNγ, a dose dependent growth inhibition in CL-2 and CL-19 cells was observed; this effect was not observed in Renca cells. Growth inhibition in CL-2 and CL-19 cell lines was associated with the intracellular induction of nitric oxide synthase (iNOS protein, resulting in a sustained elevation of nitric oxide (NO and citrulline, and a decrease in arginase activity. The inhibition of cell proliferation appears to be due to an arrest in the cell cycle. The results indicate that in certain RCC cell lines, IFNγ modulates L-arginine metabolism by shifting from arginase to iNOS activity, thereby developing a potent inhibitory mechanism to encumber tumor cell proliferation and survival. Elucidating the cellular events triggered by IFNγ in murine RCC cell lines will permit anti-tumor effects to be exploited in the development of new combination therapies that interfere with L-arginine metabolism to effectively combat RCC in patients.

  20. 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.

  1. Beta dose rates derived from gamma spectroscopy and low beta anticoincident system of various environmental materials, mainly of archaeological origin

    International Nuclear Information System (INIS)

    Beta dose-rates (BDR) have been derived from tephras, pumices and pottery of archaeological origin. The BDRs were obtained from two counting systems: (1) gamma spectrometry through appropriate conversion of gamma activity to U, Th, 40K concentration values, and (2) by counting total beta, using a gas-flow sample detector in an anticoincidence mode of counting. Assuming radioactive equilibrium in the U and Th series, the two methods of obtaining BDRs are compared. The degree of disequilibrium, the calibration, and radon escape are critically considered. The employment of either method to swift BDR measurements for the TL dating is discussed. The radioactivity measurements of tephras were used also to provenance those, as Santorini volcano might had not been the only eruption in the Aegean in the 2nd mill. B.C., it might have experienced more than one eruptive phase. BDRs in the samples ranged from 13 to about 470 mrads/year and the agreement between the two methods were in general satisfactory. 12 refs.; 2 figs.; 2 tabs

  2. 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

  3. Inhibition of L-Deleted Foot-and-Mouth Disease Virus Replication by Alpha/Beta Interferon Involves Double-Stranded RNA-Dependent Protein Kinase

    OpenAIRE

    Chinsangaram, Jarasvech; Koster, Marla; Grubman, Marvin J.

    2001-01-01

    We previously demonstrated that the ability of foot-and-mouth disease virus (FMDV) to form plaques in cell culture is associated with the suppression of alpha/beta interferon (IFN-α/β). In the present study, we used Escherichia coli-expressed porcine and bovine IFN-α or -β individually to demonstrate that each was equally effective in inhibiting FMDV replication. The block in FMDV replication appeared to be at the level of protein translation, suggesting a role for double-stranded RNA-depende...

  4. Interferon-gamma treatment kinetics among patients with active pulmonary tuberculosis

    Directory of Open Access Journals (Sweden)

    Olanisun Olufemi Adewole

    2013-01-01

    Full Text Available 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, treatment kinetics, and predictive value of IFN-γ levels during treatment of active tuberculosis. Design: Patients with pulmonary tuberculosis were recruited and subsequently followed up for 3 months during treatment with anti-TB. Peripheral blood was collected for IFN-γ assays, C-reactive protein and others followed by a Mantoux test. IFN-γ levels produced by stimulation with TB antigens were determined by ELISA and repeated measurement of IFN-γ were done at 1 and 3 months of anti-TB therapy. Chi Associations and correlations between IFN-γ were determined. Regression analysis was done to determine association between serial IFN-γ and treatment outcome. Results: We recruited 47 patients with active tuberculosis with a mean age of 34.8 ± 3.6 years and M:F ratio of 1.12:1. Six (11% were HIV positive. The mean level of IFN-γ induced by TB antigens was 629 ± 114.1 pg/ml, higher for HIV-negative PTB patients compared with HIV-positive PTB patients, 609.78 ± 723.9 pg/ml and 87.88 ± 130.0 pg/ml, respectively, P-value = 0.000. The mean level of IFN-γ induced by TB antigen increased significantly from 629 ± 114.1 pg/ml to 1023.46 + 222.8 pg/ml, P-value = 0.03 and reduced to 272.3 ± 87.7 pg/ml by the third month on anti-TB drugs, P-value = 0.001. Negative correlation was observed between the mean of baseline and chest X-ray involvement, P = 0.03. There was no significant correlation between sputum smear grade with baseline and follow-up IFN-γ levels. Three-month IFN-γ level among cured patients were higher than those with treatment failure, regression analysis showed that it does not predict outcome. Conclusion: IFN

  5. 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.

  6. 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

    shape factor plots are taken relative to the 90Y shape factor measured in the same circumstances, and it is concluded that on this basis the shapes of all three 172Tm beta groups agree with the theoretical shape for a first-forbidden unique transition. The directional correlation for the 2-(beta)2......+(gamma)0+ cascade has been measured at six energies from 1010 to 1550 keV and these results too are consistent with the assumption that the 2- rarr 2+ beta transition is purely of tensor rank 2. The data for the 2- rarr 2+ transition are analysed on the basis of the modified Bij approximation, which...... defines parameters X and Y corresponding to the relative contributions of tensor ranks 0 and 1 respectively. The shape measurement provides the limit X2 + Y2 les 0.10, whereas the angular correlation measurement gives Y = 1.64X + (0.02 plusmn0.03). The reduced transition probabilities (f1t)-1 can...

  7. Mutant U5A cells are complemented by an interferon-alpha beta receptor subunit generated by alternative processing of a new member of a cytokine receptor gene cluster.

    OpenAIRE

    Lutfalla, G; Holland, S J; Cinato, E; Monneron, D; Reboul, J.; Rogers, N C; J. M. Smith; Stark, G R; Gardiner, K.; Mogensen, K E

    1995-01-01

    The cellular receptor for the alpha/beta interferons contains at least two components that interact with interferon. The ifnar1 component is well characterized and a putative ifnar2 cDNA has recently been identified. We have cloned the gene for ifnar2 and show that it produces four different transcripts encoding three different polypeptides that are generated by exon skipping, alternative splicing and differential use of polyadenylation sites. One polypeptide is likely to be secreted and two ...

  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. First observation of $\\beta$-delayed $\\gamma$-proton decay in the $T_z$ = -2, $^{56}$Zn nucleus

    CERN Document Server

    Orrigo, S E A; Fujita, Y; Blank, B; Gelletly, W; Agramunt, J; Algora, A; Ascher, P; Bilgier, B; Cáceres, L; Cakirli, R B; Fujita, H; Ganioğlu, E; Gerbaux, M; Giovinazzo, J; Grévy, S; Kamalou, O; Kozer, H C; Kucuk, L; Kurtukian-Nieto, T; Molina, F; Popescu, L; Rogers, A M; Susoy, G; Stodel, C; Suzuki, T; Tamii, A; Thomas, J C

    2014-01-01

    We report on the first experimental observation of a very exotic decay mode at the proton drip-line, the $\\beta$-delayed $\\gamma$-proton decay, clearly seen in the $\\beta$ decay of the $T_z$ = -2, $^{56}$Zn nucleus. The $^{56}$Zn half-life and decay scheme have been determined. The decay proceeds by $\\beta$-delayed proton emission and $\\beta$-delayed $\\gamma$ de-excitation. The exotic $\\beta$-delayed $\\gamma$-proton emission was also detected in three cases. It affects the usual determination of the Gamow-Teller (GT) strength. Absolute Fermi and GT strengths have been deduced. Evidence for fragmentation of the Fermi strength due to isospin mixing is found.

  10. γ-干扰素释放试验对活动性肺结核的诊断价值%Diagnostic value of interferon gamma release assay to active pulmonary tuberculosis

    Institute of Scientific and Technical Information of China (English)

    吴静; 徐建; 张映铭; 王彩英

    2011-01-01

    Objective To evaluate the diagnostic value of interferon gamma release assay to active pulmonary tuberculosis. Methods The interferon gamma release assay based on enzyme linked immunospot assay was performed in 75 patients with suspected active pulmonary tuberculosis. And the result was compared with tuberculosis culture. Results The sensitivity, specificity and accuracy of interferon gamma release assay were 81.1%, 90.9% and 84. 0%, respectively. The sensitivity of interferon gamma release assay was higher than that of tuberculosis culture (P<0. 01). Among 23 cases af negative culture results, 16 cases were detected positive by interferon gamma release assay. Conclusion Interferon gamma release assay is highly sensitive, specific and helpful to the early and rapid detection of active pulmonary tuberculosis.%目的 评价γ-干扰素释放试验(interferon gamma release assay,IGRA)对活动性肺结核的诊断价值.方法 采用IGRA检测75例肺结核疑似病例,与结核菌培养结果进行比较.结果 IGRA诊断肺结核灵敏度为81.1%,特异度为90.9%,准确性为84.0%;IGRA灵敏度明显高于结核菌培养(P<0.01);在23例培养阴性的肺结核确诊病例中,16例IGRA阳性.结论 IGRA灵敏度高,特异度强,有助于活动性肺结核的早期、快速诊断.

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

    International Nuclear Information System (INIS)

    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

  12. THE EFFECTS OF GAMMA-INTERFERON COMBINED WITH 5-FLUOROURACIL OR 5-FLUORO-2'-DEOXYURIDINE ON PROLIFERATION AND ANTIGEN EXPRESSION IN A PANEL OF HUMAN COLORECTAL-CANCER CELL-LINES

    NARCIS (Netherlands)

    MAAS, IWHM; BOVEN, E; PINEDO, HM; SCHLUPER, HMM; Haisma, Hidde

    1991-01-01

    Gamma-Interferon (IFN-gamma) and the antimetabolites 5-fluorouracil (5-FU) and S-fluoro-2'-deoxyuridine (FUdR) were investigated as individual agents and in combination for their in vitro antiproliferative capacity and for their effect on the expression of HLA class-I antigen, carcinoembryonic antig

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

    Energy Technology Data Exchange (ETDEWEB)

    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 (/sup 60/Co) and chronic (/sup 137/Cs) gamma radiation and internal beta radiation (/sup 32/P), lethality (LD/sub 50/, LD/sub 100/), growth inhibition, and chromosome aberrations were investigated. The LD/sub 50/ and LD/sub 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.

  14. Portable alpha, beta, gamma, x and neutron radiation monitor

    International Nuclear Information System (INIS)

    Full text: Here below there is short information about new instrument developed in SPE ATOMTEX, which will be produced at the close of the year. The instrument consists of the main unit, including built-in detector Nal (Tl) of diameter 25x40 mm and photomultiplier tube, analog devices (amplifier, multichannel pulse-height analyzer of 256 channels, high-voltage power supply, LED stabilization scheme of measuring path) and digital devices (microprocessor for data processing, control and storage, liquid crystal display, interface). The main unit operates also as processing and indication device of connected external detection units: α, β-radiation contamination scintillator detection unit; x, γ-radiation detection unit with silicon detector to measure equivalent dose and equivalent dose rate and n-radiation detection unit with proportional 3He-counters. Because of scintillator detector Nal (Tl), the main unit, operating in counting mode, searches and detects effectively x- and gamma-radiation sources with the energy from 30 keV to 3 MeV. The point source of 137Cs of 50 kBq is detected at the distance of 10 cm for 2s. Ambient equivalent dose and equivalent dose rate are measured with this detector using the method of instrumental spectrum transformation into dose. In this case the energy range is from 40 keV to 3 meV. Energy relationship of readings do not exceed ± 15% with respect to the energy of 0,662 MeV. The range of ambient equivalent dose rate measurement is from 0,05 μSv/h to 0,05 mSv/h, with response time of 20 s at background change from 0,05 μSv/h to 0,1 μSv/h. The main unit operates also as selective express-radiometer, which could evaluate sample activity by single gamma-line. Measurement geometry is Marinelly's vessel of 0,5 l. The lower limit of measuring activity is 300 Bq/l without lead shield and 20 Bq/l with it with measurement time of 10 min. The unit weighs not more than 0,9 kg. External detection units connect to interface socket by turns

  15. 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

    BACKGROUND: Interferon beta is commonly used to treat patients with relapsing-remitting multiple sclerosis; however, the treatment is only partially effective in reducing relapses and progression of disability. Corticosteroids are used to treat relapses in patients with multiple sclerosis. We...... interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN) study. Patients were recruited between October, 2002, and March, 2005 from 50 neurology departments in eight countries. We included treatment-naive patients with relapsing-remitting multiple sclerosis who had an expanded disability...... 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...

  16. A revised model for AMP-activated protein kinase structure: The alpha-subunit binds to both the beta- and gamma-subunits although there is no direct binding between the beta- and gamma-subunits.

    Science.gov (United States)

    Wong, Kelly A; Lodish, Harvey F

    2006-11-24

    The 5'-AMP-activated protein kinase (AMPK) is a master sensor for cellular metabolic energy state. It is activated by a high AMP/ATP ratio and leads to metabolic changes that conserve energy and utilize alternative cellular fuel sources. The kinase is composed of a heterotrimeric protein complex containing a catalytic alpha-subunit, an AMP-binding gamma-subunit, and a scaffolding beta-subunit thought to bind directly both the alpha- and gamma-subunits. Here, we use coimmunoprecipitation of proteins in transiently transfected cells to show that the alpha2-subunit binds directly not only to the beta-subunit, confirming previous work, but also to the gamma1-subunit. Deletion analysis of the alpha2-subunit reveals that the C-terminal 386-552 residues are sufficient to bind to the beta-subunit. The gamma1-subunit binds directly to the alpha2-subunit at two interaction sites, one within the catalytic domain consisting of alpha2 amino acids 1-312 and a second within residues 386-552. Binding of the alpha2 and the gamma1-subunits was not affected by 400 mum AMP or ATP. Furthermore, we show that the beta-subunit C terminus is essential for binding to the alpha2-subunit but, in contrast to previous work, the beta-subunit does not bind directly to the gamma1-subunit. Taken together, this study presents a new model for AMPK heterotrimer structure where through its C terminus the beta-subunit binds to the alpha-subunit that, in turn, binds to the gamma-subunit. There is no direct interaction between the beta- and gamma-subunits.

  17. Risk of Tuberculosis Among Patients on Dialysis: The Predictive Value of Serial Interferon-Gamma Release Assay.

    Science.gov (United States)

    Shu, Chin-Chung; Hsu, Chia-Lin; Wei, Yu-Feng; Lee, Chih-Yuan; Liou, Hung-Hsiang; Wu, Vin-Cent; Yang, Feng-Jung; Lin, Hsien-Ho; Wang, Jann-Yuan; Chen, Jin-Shing; Yu, Chong-Jen; Lee, Li-Na

    2016-05-01

    Patients on long-term dialysis are at high risk for tuberculosis (TB). Although latent tuberculosis infection (LTBI) is good target for TB eradication, interferon-gamma release assay-defined LTBI has a high proportion of negative conversion and lacks active TB correlation among patients on dialysis.Patients on long-term dialysis were screened in multiple centers in Taiwan. QuantiFERON-TB Gold In-tube (QFT-GIT) was used to define LTBI and was performed thrice at 6-month intervals. The primary outcome was active TB diagnosed after LTBI screening. The incidence and predictive value of QFT-GIT were analyzed.The 940 dialysis patients enrolled had an average age of 59.3 years. The initial QFT-GIT results were positive in 193, including 49.6% with persistent positive results on second check. In an average follow-up period of 3 years, 7 patients had TB. Three (319.1 per 100,000 person-yrs) and 4 (141.8 per 100,000 person-yrs) of them were prevalent and incident TB cases, respectively. Persistent positive QFT-GIT for 2 and 3 times correlated with increased hazard ratio for TB (14.44 and 20.29, respectively) compared with a single positive result (hazard ratio 10.38). Among those with 3 positive QFT-GIT results, TB development rate was 4.5% and incidence rate was 1352.3 per 100,000 person-years. In contrast, none of the incident TB occurred in those with initial positive and then negative conversion of QFT-GIT.In an area of intermediate TB incidence, dialysis patients have high TB risk. LTBI status is a good predictor of TB development, especially for those with more than 1 positive result. After excluding prevalent TB cases, serial follow-up of LTBI may narrow the target population to reduce treatment costs. PMID:27258523

  18. 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. PMID:26956365

  19. Polymorphism in the First Intron of Interferon-Gamma Gene (+874T/A in Patients with BCG Adenitis

    Directory of Open Access Journals (Sweden)

    N Parvaneh

    2009-09-01

    Full Text Available "nBackground: Cytokines and specially interferon-gamma (IFN-g are largely responsible for the regulation of the protective im­mune response against mycobacterial infections. Several studies have clarified the importance of common variants of IFN-g gene regarding the susceptibility to tuberculosis. Bacille Calmette-Guérin (BCG vaccine that is used to prevent se­vere forms of tuberculosis could produce local and systemic side effects. In this study we hypothesized that the IFN-g (+874T/A polymorphism was associated with development of BCG adenitis."nMethods: Thirty patients with BCG adenitis (18 males and 12 females and 30 age and sex-matched healthy children, vacci­nated with BCG during the first two days of life were chosen. All the patients and controls were of Iranian Fars origin and the study was conducted from 2005 to 2007. DNA samples were obtained from 30 patients with BCG adenitis and 30 age and sex matched healthy vaccinees. Polymorphism at +874 was identified using allele specific polymerase chain reac­tion. Allele and genotype frequencies in cases and controls were compared using the χ2 test and odds ratios (OR and their 95% confidence intervals (CI were calculated."nResults: The minor allele (T frequency was significantly lower in patients with BCG adenitis compared to controls (35% vs. 55%, P= 0.02, OR= 0.441, 95% CI= 0.211-0.919. The Armitage trend test revealed a gradually increasing protection from the AA genotype through AT to TT (common odds ratio= 0.49; P= 0.037."nConclusion: Our data suggest that in an Iranian population, the IFN-g (+874T/A polymorphism is associated with develop­ment of BCG adenitis in the vaccinees.

  20. Interleukin-28B polymorphisms and interferon gamma inducible protein-10 serum levels in seronegative occult hepatitis C virus infection.

    Science.gov (United States)

    Bartolomé, Javier; Castillo, Inmaculada; Quiroga, Juan Antonio; Carreño, Vicente

    2016-02-01

    Polymorphisms upstream interleukin (IL)-28B gene and serum levels of interferon gamma inducible protein-10 (IP-10) are associated with spontaneous and treatment-induced hepatitis C virus (HCV) clearance. Patients with seronegative occult HCV infection are anti-HCV and serum HCV-RNA negative but have viral RNA in liver and abnormal values of liver enzymes. We examined if the rs12979860 polymorphism of IL-28B and serum IP-10 levels differ between chronic and seronegative occult CV infection. IL-28B polymorphism was determined with allele specific TaqMan probes in total DNA isolated from peripheral blood mononuclear cells and IP-10 by an enzyme-linked immunosorbent assay in serum from 99 patients with seronegative occult HCV infection and 130 untreated patients with chronic hepatitis C. IL-28B genotypes were also determined in 54 healthy volunteers. Prevalence of the IL-28B CC genotype was significantly higher in seronegative occult HCV infection (52/99; 52.5%) than in chronic hepatitis C (32/130; 24.6%, P occult HCV infection, HCV-RNA load in liver was significantly lower in those with the IL-28B CC genotype than in those with CT + TT genotypes (2.8 × 10(5)  ± 5.8 × 10(4) vs. 4.1 × 10(5)  ± 5.9 × 10(4)  copies/μg of total RNA respectively; P = 0.023). Mean serum IP-10 levels were significantly lower in patients with seronegative occult HCV infection than in patients with chronic hepatitis C (160.8 ± 17.9 vs. 288.7 ± 13.3 pg/ml respectively; P occult HCV infection in comparison with chronic hepatitis C.

  1. The function of TLR4 in interferon gamma or interleukin-13 exposed and lipopolysaccharide stimulated gingival epithelial cell cultures.

    Science.gov (United States)

    Beklen, A; Sarp, A S; Uckan, D; Tsaous Memet, G

    2014-10-01

    Gingival epithelial cells are part of the first line of host defense against infection. Toll-like receptors (TLRs) serve important immune and nonimmune functions. We investigated how interferon gamma (INF-γ) and interleukin 13 (IL-13) are involved in the TLR4 ligand-induced regulation of interleukin-8 (IL-8) effects on gingival epithelial cells. We used immunohistochemistry to localize TLR4 in ten healthy and ten periodontitis tissue specimens. Gingival epithelial cells then were primed with Th1 cytokine (INF-γ) or Th2 cytokine (IL-13) before stimulation with Escherichia coli-derived lipopolysaccharide (LPS) and enzyme-linked immunosorbent assay (ELISA) was performed to detect the level of IL-8 secretion in cell culture supernatants. Although both healthy and periodontitis gingival tissue samples expressed TLR4, the periodontitis samples showed more intense expression on gingival epithelial cells. Gingival epithelial cell cultures were primed with either INF-γ or IL-13 before stimulation with TLR4 ligand. Supernatants from co-stimulated epithelial cells exhibited IL-8 production in opposite directions, i.e., as one stimulates the release, the other reduces the release. INF-γ significantly increased TLR4 function, whereas IL-13 significantly decreased TLR4 function, i.e., production of IL-8. Pathogen associated molecular pattern-LPS, shared by many different periodonto-pathogenic bacteria, activates the gingival epithelial cells in a TLR-dependent manner. Diminished or increased TLR function in gingival epithelial cells under the influence of different Th cell types may protect or be harmful due to the altered TLR signaling.

  2. The first echinoderm gamma-interferon-inducible lysosomal thiol reductase (GILT) identified from sea cucumber (Stichopus monotuberculatus).

    Science.gov (United States)

    Ren, Chunhua; Chen, Ting; Jiang, Xiao; Luo, Xing; Wang, Yanhong; Hu, Chaoqun

    2015-01-01

    Gamma-interferon-inducible lysosomal thiol reductase (GILT) has been described as a key enzyme that facilitating the processing and presentation of major histocompatibility complex class II-restricted antigen in mammals. In this study, the first echinoderm GILT named StmGILT was identified from sea cucumber (Stichopus monotuberculatus). The StmGILT cDNA is 1529 bp in length, containing a 5'-untranslated region (UTR) of 87 bp, a 3'-UTR of 674 bp and an open reading frame (ORF) of 768 bp that encoding a protein of 255 amino acids with a deduced molecular weight of 27.82 kDa and a predicted isoelectric point of 4.73. The putative StmGILT protein possesses all the main characteristics of known GILT proteins, including a signature sequence, a reductase active site CXXC, twelve conserved cysteines, and two potential N-linked glycosylation sites. For the gene structure, StmGILT contains four exons separated by three introns. In the promoter region of StmGILT gene, an NF-κB binding site and an IFN-γ activation site were found. The thiol reductase activity of recombinant StmGILT protein was also demonstrated in this study. In addition, the highest level of mRNA expression was noticed in coelomocytes of S. monotuberculatus. In in vitro experiments performed in coelomocytes, the expression of StmGILT mRNA was significantly up-regulated by lipopolysaccharides (LPS), inactivated bacteria or polyriboinosinic polyribocytidylic acid [poly (I:C)] challenge, suggested that the sea cucumber GILT might play critical roles in the innate immune defending against bacterial and viral infections. PMID:25449705

  3. 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.

  4. $\\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.

  5. Feasibility and diagnostic utility of antigen-specific interferon-gamma responses for rapid immunodiagnosis of tuberculosis using induced sputum.

    Directory of Open Access Journals (Sweden)

    Tamaryn J Cashmore

    Full Text Available BACKGROUND: The diagnosis of smear-negative or sputum-scarce tuberculosis (TB is problematic as culture takes several weeks and representative biological samples are difficult to obtain. RD-1 antigen-specific interferon-gamma release assays (IGRAs are sensitive and specific blood-based tests for the diagnosis of M. tuberculosis infection. The feasibility and diagnostic utility of this rapid immunodiagnostic assay, using cells from induced sputum, is unknown. METHODOLOGY/PRINCIPAL FINDINGS: Cells isolated from induced sputum were co-cultured with ESAT-6 and CFP-10 antigens using a standardized enzyme-linked immunospot (ELISPOT assay (T-SPOT.TB in 101 consecutively recruited TB suspects or non-TB controls. An optimization phase using 28 samples was followed by a validation phase using samples from 73 participants (20 with definite or probable TB, and 48 with non-TB. Despite optimization of sputum processing 65/73 (89% of the IGRAs in the validation phase were inconclusive. 44/73 (60% tests failed due to sputum induction-related factors [sputum induction-related adverse events (n = 5, inadequate sputum volume (n = 8, non-homogenisable sputum (n = 7, and insufficient numbers of cells to perform the assay (n = 24], whilst 20/73 (27% tests failed due T-SPOT.TB assay-related factors [excessive debris precluding reading of spots in the ELISPOT well (n = 6, failure of the positive control (n = 11, or high spot count in the negative control (n = 3]. Only 8/73 (11% of the available samples could therefore be correctly categorized (7 definite or probable TB, and 1 non-TB patient. Thus, 13/20 (65% of the definite or probable TB cases remained undiagnosed. CONCLUSIONS/SIGNIFICANCE: Rapid immunodiagnosis of pulmonary TB by antigen-specific IFN-gamma ELISPOT responses, using cells from induced sputum, is possible. However, the test, in its current ELISPOT format, is not clinically useful because the majority of the assays are inconclusive.

  6. Role of interferon gamma and tumor necrosis factor-related apoptosis-inducing ligand receptor 1 single nucleotide polymorphism in natural clearance and treatment response of HCV infection.

    Science.gov (United States)

    Azam, Sikandar; Manzoor, Sobia; Imran, Muhammad; Ashraf, Javed; Ashraf, Sarah; Resham, Saleha; Ghani, Eijaz

    2015-05-01

    Hepatitis C virus (HCV) pathogenesis and treatment outcomes are multifactorial phenomena involving both viral and host factors. This study was designed to determine the role of tumor necrosis factor-related apoptosis-inducing ligand receptor 1(TRAIL-R1) and interferon gamma (IFN-γ) genetic mutations in susceptibility and response to interferon-based therapy of hepatitis C virus (HCV) infection. The detection of TRAIL-R1 rs4242392 and IFN-γ rs2069707 single nucleotide polymorphisms was completed in 118 chronic HCV patients and 96 healthy controls by allele-specific polymerase chain reaction and restriction fragment length polymorphisms polymerase chain reaction. Patients were further categorized into sustained virological responder (SVR) and nonresponder (NR) groups on the basis of their response to interferon-based therapy for HCV infection. Real-time PCR was used for HCV quantification. HCV genotyping was performed by Ohno's method. The results demonstrated that the distribution of the TRAIL-R1 rs4242392TT genotype was significantly higher in the SVR group (78%) compared to the NR group (36%). It showed that chronic HCV patients possessing the TRAIL-R1 rs4242392TT genotype are better responders to interferon-based therapy (p0.05). The distribution of IFN-γ rs2069707 was the opposite to TRAIL-R1 rs4242392 prevalence, that is, there was high distribution of the IFN-γ rs2069707GG genotype in patients and healthy controls (p0.05). In conclusion, genetic variation of TRAIL-R1 rs4242392 is linked with response to interferon-based therapy for HCV infection, and genetic variation IFN-γ rs2069707 is associated with natural clearance of HCV infection.

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

    International Nuclear Information System (INIS)

    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

  8. Serum S100B in primary progressive multiple sclerosis patients treated with interferon-beta-1a

    Directory of Open Access Journals (Sweden)

    Miller David H

    2004-10-01

    Full Text Available Abstract S100B belongs to a family of calcium-binding proteins implicated in intracellular and extracellular regulatory activities. This study of serum S100B in primary progressive multiple sclerosis (PPMS is based on data obtained from a randomized, controlled trial of Interferon β-1a in subjects with PPMS. The key questions were whether S100B levels were associated with either disability or MRI findings in primary progressive MS and whether Interferon β-1a has an effect on their S100B levels. Serial serum S100B levels were measured using an ELISA method. The results demonstrated that serum S100B is not related to either disease progression or MRI findings in subjects with primary progressive MS given Interferon β-1a. Furthermore there is no correlation between S100B levels and the primary and secondary outcome measures.

  9. Use of ESAT-6-CFP-10 fusion protein in the bovine interferon-gamma ELISPOT assay for diagnosis of Mycobacterium bovis infection in cattle.

    Science.gov (United States)

    Parthasarathy, Sugumar; Veerasami, Maroudam; Appana, Gangadharrao; Chandran, Dev; Das, Dipankar; Srinivasan, Villuppanoor Alwar

    2012-09-01

    Bovine tuberculosis (BTB) is a chronic bacterial disease, and a major animal health problem with zoonotic implications. Screening of mycobacterial infections in bovines is traditionally done using the single intradermal tuberculin test. Though the test is widely used, it has its own disadvantages and they include its inability to distinguish between pathogenic and non-pathogenic mycobacterial infections owing to its low specificity. Furthermore, the associated operative difficulties of this test have driven the quest for discovery of new antigens and diagnostic assays leading to the development of the interferon (IFN)- test. Presently, combinatorial testing using the skin test and the interferon gamma assays are being used in the diagnosis of BTB in various control and surveillance programs. In this study, we report the cloning, expression and purification of ESAT-6-CFP-10 fusion protein and its further use in the development of the IFN- gamma ELISPOT assay for accurate diagnosis of BTB in cattle. The BTB diagnosis employing the ELISPOT assay was evaluated using peripheral blood mononuclear cells from culture positive and culture negative cattle. The ELISPOT assay showed higher specificity and sensitivity in detecting BTB when a recombinant ESAT-6-CFP-10 fusion protein was used. The present study indicated that the usefulness of the fusion protein can replace the ESAT-6, CFP-10 or combination of both proteins for detecting BTB in IFN-gamma ELISPOT assay. PMID:22691409

  10. Kinetically-controlled thin-film growth of layered $\\beta$- and $\\gamma-$Na$_{x}$CoO$_{2}$ cobaltate

    OpenAIRE

    SON, J.Y.; Kim, Bog G.; Cho, J. H.

    2005-01-01

    We report growth characteristics of epitaxial $\\beta$-Na$_{0.6}$CoO$_{2}$ and $\\gamma$-Na$_{0.7}$CoO$_{2}$ thin films on (001) sapphire substrates grown by pulsed-laser deposition. Reduction of deposition rate could change structure of Na$_{x}$CoO$_{2}$ thin film from $\\beta$-phase with island growth mode to $\\gamma$-phase with layer-by-layer growth mode. The $\\gamma$-Na$_{0.7}$CoO$_{2}$ thin film exhibits spiral surface growth with multiterraced islands and highly crystallized texture compar...

  11. 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.

  12. Expression of interleukin 2 receptors and binding of interleukin 2 by gamma interferon-induced human leukemic and normal monocytic cells

    OpenAIRE

    1985-01-01

    Gamma interferon induced surface expression of interleukin 2 (IL-2) receptors on normal human monocytes and the monocytoid cell lines U937 and HL60. These receptors were detected by anti-IL-2 receptor monoclonal antibodies, and U937 IL-2 receptors were indistinguishable from T lymphocyte IL-2 receptors by immunoprecipitation. Also, U937 IL- 2 receptors bound biologically active IL-2. These results suggest a role for monocyte IL-2 receptors in T cell/monocyte interaction during an immune respo...

  13. Evaluation of the Immune Response to Interferon Gamma Release Assay and Tuberculin Skin Test Among BCG Vaccinated Children in East of Egypt: A Cross-Sectional Study.

    Science.gov (United States)

    Beshir, Mohamed Refaat; Zidan, Alaa Ebrahim; El-Saadny, Hosam Fathi; Ramadan, Raghdaa Abdelaziz; Karam, Nehad Ahmed; Amin, Ezzat Kamel; Mohamed, Marwa Zakaria; Abdelsamad, Nahla Mohamed

    2016-04-01

    Bacille Calmette-Guérin vaccine (BCG) vaccination is used routinely in most of countries, especially developing one. The efficacy of the BCG vaccination generally decreases with time. The tuberculin skin test (TST) is a most popular diagnostic test for suspicion of tuberculosis (TB) in children till now, but it has many false positives. The interferon-gamma release assay (IGRA) is more specific than TST for detection of childhood TB, as it is more specific to Mycobacterium tuberculosis.Evaluate the interferon gamma response and TST reaction in BCG vaccinated children in east of Egypt.150 children were included in the study aged 1 month to 12 years; the collected data from the children included, full history taking, clinical examination, examination for the presence or absence of BCG scar under direct light. All the children had performed TST, IGRA.TST was done for all studied group reveal 51.3% with size of reaction <5 mm, 39.3% with size of reaction = 5 to 9 mm while 9.3% with size of reaction ≥10 mm. Mean size of reaction was 4.07 mm. Interferon gamma release assay was done for all studied group reveal 5 children (3.3%) with positive test. There was significant difference between the size of TST reaction and age (P < 0.01) with old children were more frequent to show positive reaction. Also, children with age range 1 month to 1 year were frequently have negative IGRA test, while children with age range 4 years to 12 years were frequently have positive test (P < 0.01). There was moderate agreement between IGRA and TST results (Kappa [κ] = 0.475). With high agreement between IGRA and TST results in children with absent BCG scar (κ = 1000).Therefore, Interferon gamma release assays have higher specificity and lower cross-reactions with BCG vaccination and nontuberculous Mycobacteraie than TST. PMID:27124042

  14. The effects of excessive iodine intake on mRNA expressions of interleukin-23,interleukin-17 and gamma interferon in BABL/c mice

    Institute of Scientific and Technical Information of China (English)

    周晓丽

    2014-01-01

    Objective To observe the effects of excessive iodine intake on autoimmune thyroiditis and mRNA expressions of interleukin-17(IL-17),interleukin-23(IL-23)and gamma interferon(IFN-γ)in thyroid gland and spleen of mice and to further explore the pathogenesis of iodine overdose induced autoimmune thyroiditis.Methods According to body mass,seven to eight weeks old BALB/c mice(body mass 20-25 g,half male and half female)were selected and divided into 4 groups(12 mice in each

  15. 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.

  16. Low-level gamma spectrometry using beta coincidence and Compton suppression.

    Science.gov (United States)

    Grigorescu, E L; De Felice, P; Razdolescu, Anamaria-Cristina; Luca, A

    2004-01-01

    A low-level gamma-ray spectrometry system was developed using a Ge(Li) detector with 6% relative efficiency coupled to a 2pi beta plastic detector for coincidence selection and a massive NaI(Tl) detector for Compton suppression. The integral background count rate for (50-1500)keV was 0.5 s(-1)kg(-1) (Ge), using only beta coincidences. With Compton suppression, a value of 0.25 s(-1)kg(-1) (Ge) was obtained. Spectra with and without Compton suppression were studied for 60Co, 137Cs and 152Eu point sources. Considerations are made concerning the Compton suppression advantages in different situations. PMID:15177343

  17. Effect of treatment with interferon-gamma and concanavalin A on the course of infection of mice with Salmonella typhimurium strain LT-2

    Science.gov (United States)

    Gould, Cheryl L.; Sonnenfeld, Gerald

    1987-01-01

    The effect of pretreatment of mice with 34 units/day, for five days, of interferon-gamma (IFN-gamma) on the course of infection with LD50 of Salmonella typhimurium strain LT-2 was assessed, using two IFN preparations: (1) a hybridoma supernatant fluid containing concanavalin-A-induced IFN-gamma activity and (2) pure murine IFN-gamma produced by recombinant DNA technology. The hybridoma supernatant-treated Salmonella-infected mice were found to die faster than mice treated only with Salmonella. Pure murine IFN-gamma was found to protect infected mice significantly, with 95 percent of mice surviving LD50 infection. In contrast, the Salmonella-infected mice treated with hybridoma supernatant were found to die faster than the Salmonella-infected untreated controls. Mice treated with concanavalin A alone prior to infection with S. typhimurium died more quickly than the untreated infected controls, suggesting that contamination with concanavalin A had a detrimental effect on mice survival.

  18. Effect of extracellular pH on recombinant alpha1beta2gamma2 and alpha1beta2 GABAA receptors.

    Science.gov (United States)

    Mercik, Katarzyna; Pytel, Maria; Cherubini, Enrico; Mozrzymas, Jerzy W

    2006-08-01

    Recently, we have reported that extracellular protons allosterically modulated neuronal GABA(A) receptors [Mozrzymas, J.W., Zarnowska, E.D., Pytel, M., Mercik, K., 2003a. Modulation of GABA(A) receptors by hydrogen ions reveals synaptic GABA transient and a crucial role of desensitiztion process. Journal of Neuroscience 23, 7981-7992]. However, GABAARs in neurons are heterogeneous and the effect of hydrogen ions depends on the receptor subtype. In particular, gamma2 subunit sets the receptor sensibility to several modulators including protons. However, the mechanisms whereby protons modulate gamma2-containing and gamma2-free GABAARs have not been fully elucidated. To this end, current responses to ultrafast GABA applications were recorded for alpha1beta2gamma2 and alpha1beta2 receptors at different pH values. For both receptor types, increase in pH induced a decrease in amplitudes of currents elicited by saturating [GABA] but this effect was stronger for alpha1beta2 receptors. In the case of alpha1beta2gamma2 receptors, protons strongly affected the current time course due to a down regulation of binding and desensitization rates. This effect was qualitatively similar to that described in neurons. Protons strongly influenced the amplitude of alpha1beta2 receptor-mediated currents but the effect on their kinetics was weak suggesting a predominant direct non-competitive inhibition with a minor allosteric modulation. In conclusion, we provide evidence that extracellular protons strongly affect GABAA receptors and that, depending on the presence of the gamma2 subunit, the modulatory mechanisms show profound quantitative and qualitative differences.

  19. CD8+ T Cell Response to Gammaherpesvirus Infection Mediates Inflammation and Fibrosis in Interferon Gamma Receptor-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Brigid M O'Flaherty

    Full Text Available Idiopathic pulmonary fibrosis (IPF, one of the most severe interstitial lung diseases, is a progressive fibrotic disorder of unknown etiology. However, there is growing appreciation for the role of viral infection in disease induction and/or progression. A small animal model of multi-organ fibrosis, which involves murine gammaherpesvirus (MHV68 infection of interferon gamma receptor deficient (IFNγR-/- mice, has been utilized to model the association of gammaherpesvirus infections and lung fibrosis. Notably, several MHV68 mutants which fail to induce fibrosis have been identified. Our current study aimed to better define the role of the unique MHV68 gene, M1, in development of pulmonary fibrosis. We have previously shown that the M1 gene encodes a secreted protein which possesses superantigen-like function to drive the expansion and activation of Vβ4+ CD8+ T cells. Here we show that M1-dependent fibrosis is correlated with heightened levels of inflammation in the lung. We observe an M1-dependent cellular infiltrate of innate immune cells with most striking differences at 28 days-post infection. Furthermore, in the absence of M1 protein expression we observed reduced CD8+ T cells and MHV68 epitope specific CD8+ T cells to the lungs-despite equivalent levels of viral replication between M1 null and wild type MHV68. Notably, backcrossing the IFNγR-/- onto the Balb/c background, which has previously been shown to exhibit weak MHV68-driven Vβ4+ CD8+ T cell expansion, eliminated MHV68-induced fibrosis-further implicating the activated Vβ4+ CD8+ T cell population in the induction of fibrosis. We further addressed the role that CD8+ T cells play in the induction of fibrosis by depleting CD8+ T cells, which protected the mice from fibrotic disease. Taken together these findings are consistent with the hypothesized role of Vβ4+ CD8+ T cells as mediators of fibrotic disease in IFNγR-/- mice.

  20. Association between interferon gamma receptor 1-56C/T gene polymorphism and tuberculosis susceptibility: a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Wang Wei; Ren Weicong; Zhang Xuxia; Liu Yi; Li Chuanyou

    2014-01-01

    Background Genetic variations in the interferon-gamma (IFN-γ) receptor 1 gene (IFNGR1) may contribute to tuberculosis (TB) risk in different populations.Many studies have investigated the relationship between IFNGR1 56C/T polymorphism and the susceptibility to TB,but have yielded conflicting results.A comprehensive meta-analysis is needed to provide a more accurate estimation of the relationship between them.Methods A literature search based on a combination of manual and computer-based methods was conducted on four English databases (PubMed,Science Direct,SpringerLink,and EBSCO) and three Chinese databases (Wanfang,CQVIP,and Chinese National Knowledge Infrastructure databases).Pooled odds ratios (ORs) and 95% confidence intervals (95% Cls) were calculated using either the fixed-effects model or the random-effects model for different genetic models based on the heterogeneity examination.Results A total of six studies comprising 1 497 confirmed TB cases and 1 802 controls were included in this meta-analysis.Overall,no significant association was observed between IFNGR1-56C/T polymorphism and TB susceptibility (C vs.T,OR=0.90,95% Cl 0.69-1.17; CC vs.TT,OR=0.87,95% Cl 0.65-1.18; TC vs.TT,OR=-1.031,95% Cl 0.872-1.219; CC+TC vs.TT,OR=0.89,95% Cl 0.64-1.26; CC vs.TC+TT,OR=0.92,95% Cl 0.66-1.29).In subgroup analysis,a significant association was found in the dominant model (CC+TC vs.TT,OR=1.24,95% Cl 1.02-1.51) in Africans,but not in Asians or Caucasians.Conclusions Our meta-analysis did not provide enough powerful evidence to identify a significant association between IFNGR1-56C/T polymorphism and TB susceptibility in the overall population.In subgroup analysis,it indicates that IFNGR1-56C/T is possibly associated with increased TB risk in Africans,but not in Asians or Caucasians.However,larger sample size and better-designed case-control studies are needed to validate these findings.

  1. 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)

  2. On evaluated nuclear data for beta-delayed gamma rays following of special nuclear materials

    International Nuclear Information System (INIS)

    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)

  3. Contribution to decay heat calculation: fission product mean beta and gamma assessment

    International Nuclear Information System (INIS)

    Following a reactor shutdown, after the fission chain process has completely faded out, a significant quantity of energy (around seven per cent of the total power of the reactor) continues to be generated in the core. This is known as residual power or decay heat. The principal source of this energy is due to the radioactive decay of fission products and is at any time equal to the sum of the powers released by these different nuclei (P = Σ = Pi). Each of the powers Pi is the product of three terms: the concentration of the relevant nuclide, its decay constant and its mean decay energy. The evaluation of the first two term is straightforward. On the other hand the evaluation of the mean energies presents some difficulties due to a lack of data in beta and gamma spectra of some fission products. This study intends, after a critical analysis of the current method of evaluation of the mean energies, to propose a new model for this calculation. The new model tested on several well known nuclides, has been proved correct and precise. It has then been applied to approximatively sixty nuclides among the lesser known ones. The results obtained have lead to a better prediction of both beta and gamma ray components of the residual power. Consequently, this new model, which allows to take into account the lack of beta branching ratio corresponding to the highest levels of the product nucleus in the beta decay reaction, can be adopted to replace the current method, for calculation of the mean energies of fission products, especially in the case of the lesser known nuclides

  4. Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells.

    OpenAIRE

    Gauldie, J.; C. Richards; Harnish, D; Lansdorp, P.; Baumann, H

    1987-01-01

    One of the oldest and most preserved of the homeostatic responses of the body to injury is the acute phase protein response associated with inflammation. The liver responds to hormone-like mediators by the increased synthesis of a series of plasma proteins called acute phase reactants. In these studies, we examined the relationship of hepatocyte-stimulating factor derived from peripheral blood monocytes to interferon beta 2 (IFN-beta 2), which has been cloned. Antibodies raised against fibrob...

  5. Modeling the Production of Beta-Delayed Gamma Rays for the Detection of Special Nuclear Materials

    Energy Technology Data Exchange (ETDEWEB)

    Hall, J M; Pruet, J A; Brown, D A; Descalle, M; Hedstrom, G W; Prussin, S G

    2005-02-14

    The objective of this LDRD project was to develop one or more models for the production of {beta}-delayed {gamma} rays following neutron-induced fission of a special nuclear material (SNM) and to define a standardized formatting scheme which will allow them to be incorporated into some of the modern, general-purpose Monte Carlo transport codes currently being used to simulate inspection techniques proposed for detecting fissionable material hidden in sea-going cargo containers. In this report, we will describe a Monte Carlo model for {beta}-delayed {gamma}-ray emission following the fission of SNM that can accommodate arbitrary time-dependent fission rates and photon collection histories. The model involves direct sampling of the independent fission yield distributions of the system, the branching ratios for decay of individual fission products and spectral distributions representing photon emission from each fission product and for each decay mode. While computationally intensive, it will be shown that this model can provide reasonably detailed estimates of the spectra that would be recorded by an arbitrary spectrometer and may prove quite useful in assessing the quality of evaluated data libraries and identifying gaps in the libraries. The accuracy of the model will be illustrated by comparing calculated and experimental spectra from the decay of short-lived fission products following the reactions {sup 235}U(n{sub th}, f) and {sup 239}Pu(n{sub th}, f). For general-purpose transport calculations, where a detailed consideration of the large number of individual {gamma}-ray transitions in a spectrum may not be necessary, it will be shown that a simple parameterization of the {gamma}-ray source function can be defined which provides high-quality average spectral distributions that should suffice for calculations describing photons being transported through thick attenuating media. Finally, a proposal for ENDF-compatible formats that describe each of the models and

  6. Interferon-gamma and interleukin-10 levels in serum and saliva are related to different types of oral lichen planus

    Institute of Scientific and Technical Information of China (English)

    Zhu Jian-hua; Liu Na; Zhao Chang-rong; Liu Ji-guang

    2015-01-01

    Abstract BACKGROUND: Many cytokines can be detected in saliva and serum, and have more clinical significance in the diagnosis, prognosis and treatment of oral mucosa disease. OBJECTIVE: To compare the interferon-γ and interleukin-10 levels in serum and saliva of patients with different types of oral lichen planus and to explore the feasibility of saliva samples as a substitute of blood samples to study the interferon-γ and interleukin-10 levels in serum and saliva. METHODS:Totaly 45 patients with oral lichen planus admitted at the Department of Periodontology, the Stomatological Hospital of Jiamusi University from January to July 2014 were enroled, including 15 cases of erosion type (erosion group), 15 cases of congestive erythema (congestive erythema group) and 15 cases of reticulate type (reticulate group). Another 15 healthy controls admitted for physical examination at the Department of Physical Examination, the Stomatological Hospital of Jiamusi University were enroled as controls. ELISA method was used to detect the interferon-γ and interleukin-10 levels in serum and saliva in the four groups. RESULTS AND CONCLUSION: Compared with the control group, the interferon-γ levels in serum and saliva were lower in the other three groups (P < 0.01), while there were significant differences in the interferon-γ level among the patients with different types of oral lichen planus (P < 0.01). The interleukin-10 levels in serum and saliva were significantly higher in the erosion group and congestive erythema group than those in the control group (P < 0.01 orP < 0.05) and reticulate groupP < 0.01 orP < 0.05). Experimental findings suggest that the levels of interferon-γ and interleukin-10 in serum and saliva are highly correlated in patients with different types of oral lichen planus, and saliva samples can be instead of blood samples to detect the levels of interferon-γ and interleukin-10 in patients with oral lichen planus.

  7. Persistence on therapy and propensity matched outcome comparison of two subcutaneous interferon beta 1a dosages for multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Tomas Kalincik

    Full Text Available OBJECTIVES: To compare treatment persistence between two dosages of interferon β-1a in a large observational multiple sclerosis registry and assess disease outcomes of first line MS treatment at these dosages using propensity scoring to adjust for baseline imbalance in disease characteristics. METHODS: Treatment discontinuations were evaluated in all patients within the MSBase registry who commenced interferon β-1a SC thrice weekly (n = 4678. Furthermore, we assessed 2-year clinical outcomes in 1220 patients treated with interferon β-1a in either dosage (22 µg or 44 µg as their first disease modifying agent, matched on propensity score calculated from pre-treatment demographic and clinical variables. A subgroup analysis was performed on 456 matched patients who also had baseline MRI variables recorded. RESULTS: Overall, 4054 treatment discontinuations were recorded in 3059 patients. The patients receiving the lower interferon dosage were more likely to discontinue treatment than those with the higher dosage (25% vs. 20% annual probability of discontinuation, respectively. This was seen in discontinuations with reasons recorded as "lack of efficacy" (3.3% vs. 1.7%, "scheduled stop" (2.2% vs. 1.3% or without the reason recorded (16.7% vs. 13.3% annual discontinuation rate, 22 µg vs. 44 µg dosage, respectively. Propensity score was determined by treating centre and disability (score without MRI parameters or centre, sex and number of contrast-enhancing lesions (score including MRI parameters. No differences in clinical outcomes at two years (relapse rate, time relapse-free and disability were observed between the matched patients treated with either of the interferon dosages. CONCLUSIONS: Treatment discontinuations were more common in interferon β-1a 22 µg SC thrice weekly. However, 2-year clinical outcomes did not differ between patients receiving the different dosages, thus replicating in a registry dataset derived from "real

  8. The gamma-interferon test: its usefulness in a bovine tuberculosis survey in African buffaloes (Syncerus caffer) in the Kruger National Park.

    Science.gov (United States)

    Grobler, D G; Michel, Anita L; De Klerk, Lin-Mari; Bengis, R G

    2002-09-01

    A survey to determine the bovine tuberculosis status of buffalo herds north of the Olifants River in the Kruger National Park was conducted, using a new diagnostic approach. Diagnosis of Mycobacterium bovis infection was accomplished using the gamma-interferon assay technique in 608 adult buffaloes out of a total of 29 discreet herds. The animals were immobilized in groups of 10-15, bled, individually marked and then revived and released on site. As soon as test results were available (after 26-36 h), the same buffalo herd was relocated by tracking the frequency of a radio-collar previously fitted to one adult cow per group during the initial operation. Bovine reactors were identified, darted and euthanased from the helicopter. Necropsy and culture findings of all culled buffaloes showed excellent correlation with the results of the ante-mortem gamma-interferon test. The survey revealed that over and above the two positive herds that had been identified during a previous survey carried out in 1996, there were three additional, but previously unidentified, infected herds in the region north of the Olifants River.

  9. 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.

  10. Development of rheumatoid arthritis during treatment of multiple sclerosis with interferon beta 1-a. Coincidence of two conditions or a complication of treatment: A case report.

    Science.gov (United States)

    Hojjati, Seyed Mohammad Masood; Heidari, Behzad; Babaei, Mansour

    2016-09-01

    Coexistence of multiple sclerosis (MS) with other autoimmune diseases has been attributed to common background genetic or environmental factors. This study presents development of rheumatoid arthritis (RA) during treatment of MS. The MS was confirmed by the Mc Donald criteria and the diagnosis of RA was confirmed by the ACR/EULAR criteria. A 35 years old women with 9 years of MS who was receiving interferon beta 1-a (INF) for 7 years and who did not respond to conventional therapy of RA over 8 months developed clinical manifestations of RA. But a rapid response was observed after discontinuation of INF. These findings suggest a possible contribution of INF in the development of RA. PMID:27489727

  11. Durability and shielding performance of borated Ceramicrete coatings in beta and gamma radiation fields

    International Nuclear Information System (INIS)

    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

  12. Durability and shielding performance of borated Ceramicrete coatings in beta and gamma radiation fields

    Science.gov (United States)

    Wagh, Arun S.; Sayenko, S. Yu.; Dovbnya, A. N.; Shkuropatenko, V. A.; Tarasov, R. V.; Rybka, A. V.; Zakharchenko, A. A.

    2015-07-01

    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.

  13. 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.

  14. 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.

  15. Missense splice variant (g.20746A>G, p.Ile183Val) of interferon gamma receptor 1 (IFNGR1) coincidental with mycobacterial osteomyelitis - a screen of osteoarticular lesions.

    Science.gov (United States)

    Bińczak-Kuleta, Agnieszka; Szwed, Aleksander; Walter, Mark R; Kołban, Maciej; Ciechanowicz, Andrzej; Clark, Jeremy S C

    2016-08-01

    Previously, dominant partial interferon-gamma receptor 1 (IFN-g-R1) susceptibility to environmental mycobacteria was found with IFNGR1 deletions or premature stop. Our aim was to search for IFNGR1 variants in patients with mycobacterial osteoarticular lesions. Biopsies from the patients were examined for acid-fast bacilli, inflammatory cell infiltration, and mycobacterial niacin. Mycobacterial rRNA was analyzed using a target-amplified rRNA probe test. Peripheral-blood-leukocyte genomic DNA was isolated from 19 patients using the QIAamp DNA Mini Kit, and all IFNGR1 exons were sequenced using an ABIPRISM 3130 device. After the discovery of an exon 5 variant, a Polish newborn population sample (n = 100) was assayed for the discovered variant. Splice sites and putative amino acid interactions were analyzed. All patients tested were positive for mycobacteria; one was heterozygous for the IFNGR1 exon 5 single-nucleotide-missense substitution (g.20746A>G, p.Ile183Val). No other variant was found. The splice analysis indicated the creation of an exonic splicing silencer, and alternatively, molecular graphics indicated that the p.Ile183Val might alter beta-strand packing (loss of van der Waals contacts; Val183/Pro205), possibly altering the IFN-g-R1/IFN-g-R2 interaction. The probability of non-deleterious variant was estimated as genes affecting Type 1 T-helper-cell-mediated immunity. PMID:27483180

  16. MHC2TA mRNA levels and human herpesvirus 6 in multiple sclerosis patients treated with interferon beta along two-year follow-up

    Directory of Open Access Journals (Sweden)

    Dominguez-Mozo Maria Inmaculada

    2012-09-01

    Full Text Available Abstract Background In previous studies we found that MHC2TA +1614 genotype frequency was very different when MS patients with and without human herpesvirus 6 (HHV-6 in serum samples were compared; a different clinical behavior was also described. The purpose of the study was: 1. To evaluate if MHC2TA expression in MS patients was influenced by interferon beta (IFN-beta treatment. 2. To study MHC2TA expression in MS patients with and without minor allele C. 3. To analyze the relation between MHC2TA mRNA levels and HHV-6 active infection in MS patients. Methods Blood and serum samples of 154 MS patients were collected in five programmed visits: basal (prior to beginning IFN-beta treatment, six, twelve, eighteen and twenty-four months later. HHV-6 in serum and MHC2TA mRNA levels were evaluated by PCR and RT-PCR, respectively. Neutralizing antibodies (NAbs against IFN-beta were analyzed by the cytopathic effect assay. Results We found that MHC2TA mRNA levels were significantly lower among MS patients with HHV-6 active infection at the basal visit (without treatment than in those MS patients without HHV-6 active infection at the basal visit (p = 0.012; in all the positive samples we only found variant A. Furthermore, 58/99 (58.6% MS patients without HHV-6 along the five programmed visits and an increase of MHC2TA expression after two-years of IFN-beta treatment were clinical responders vs. 5/21 (23.8% among those MS patients with HHV-6 and a decrease of MHC2TA mRNA levels along the two-years with IFN-beta treatment (p = 0.004; no differences were found between patients with and without NAbs. Conclusions MHC2TA mRNA levels could be decreased by the active replication of HHV-6; the absence of HHV-6 in serum and the increase of MHC2TA expression could be further studied as markers of good clinical response to IFN-beta treatment.

  17. 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 BACKGROUND: 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. OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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

  18. Pathway for interferon-gamma to promote the differentiation of cholinergic neurons in rat embryonic basal forebrain/septal nuclei

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: The supernatant of interferon-gamma (IFN γ ) co-cultured with neonatal rat cortical glia can promote the cells in embryonic basal forebrain/septal nuclei to differentiate into cholinergic neurons, but the mechanism is still unclear.OBJECTIVE: To analyze the pathways for IFN γ to promote the differentiation of primarily cultured cholinergic neurons in rat embryonic basal forebrain/septal nuclei through culture in different conditioned medium.DESIGN: A controlled experiment taking cells as the observational target.SETTINGS: Department of Biochemistry and Molecular Biology, Youjiang Medical College for Nationalities; Department of Cell Biology, Beijing University Health Science Center.MATERIALS: Sixty-four pregnant Wistar rats for 16 days (250 - 350 g) and 84 Wistar rats (either male or female, 5 - 7 g) of 0 - 1 day after birth were provided by the experimental animal department of Beijing University Health Science Center. Rat IFN γ were provided by Gibco Company; Glial fibrillary acidic protein by Huamei Company.METHODS: The experiments were carried out in the Department of Cell Biology, Beijing University Health Science Center and Daheng Image Company of Chinese Academy of Science from July 1995 to December 2002. ① Interventions: The nerve cells in the basal forebrain/septal nuclei of the pregnant Wistar rats for 16 days were primarily cultured, and then divided into four groups: Blank control group (not any supernatant and medium was added); Control group (added by mixed glial cell or astrocyte conditioned medium); IFN γ group (added by mixed glial cell or astrocyte conditioned medium+IFN γ ). Antibody group (added by mixed glial cell or astrocyte conditioned medium+IFN γ +Ab-IFN γ ). Mixed glial cell or astrocyte conditioned medium was prepared using cerebral cortex of Wistar rats of 0 - 1 day after birth. ② Evaluation: The immunohistochemical method was used to perform the choline acetyltransferase (ChAT) staining of cholinergic neurons

  19. Effect of Moderate Exercise on Serum Interferon-Gamma and Interleukin-17 Levels in the Morphine Withdrawal Period

    Directory of Open Access Journals (Sweden)

    Heidarianpour

    2016-02-01

    Full Text Available Background Drug addiction triggers the infliction of a variety of diseases. Various subjects have indicated that during the withdrawal syndrome period, the immune system is weakened. Objectives This study aimed to investigate the changes in serum levels of interferon-gamma (IFN-γ and interleukin-17 (IL-17 during the morphine withdrawal syndrome induced by 8 weeks of moderate exercise and their effects on the immune system function. Materials and Methods Twenty-four male Wistar rats (220 ± 10 g were divided into four groups (n = 6: healthy control (HC, addicted control (AC, healthy trained (HT, and addicted trained (AT groups. AC and AT groups were made addicted to morphine sulfate (0.4 mg/mL in 21 days. To ensure their dependence on morphine, naloxone (3 mg/kg, i.p. was injected into the body of a number of the rats. HT and AT groups were made to run on a treadmill 5 days per week for 8 weeks while time and speed gradually increased. Both prior to the exercises and 24 hours after the last training session, blood samples were collected from all the animals, and serum IFN-γ and IL-17 serum levels were measured using the ELISA method. This research was performed at the Bu-Ali Sina University, Hamadan, Iran. Results After 8 weeks of exercise, a significant increase was observed in the serum IFN-γ level in the HT group (251.17 ± 13.045 in comparison with the HC group (234 ± 12.884 (P = 0.045. Furthermore, the serum IFN-γ level in the AT group (218.33 ± 5.164 in comparison to the AC group (190.67 ± 8.477 showed a significant increase (P = 0.000. In addition, the serum level of IFN-γ in the HT group showed a significant increase compared to the AT group (P = 0.000. After 8 weeks of exercise, there was a significant decrease in the serum IL-17 level in the HT group (22.67 ± 4.46 compared with the HC group (38.17 ± 7.68 (P = 0.005. In addition, a significant decrease was observed in serum IL-17 in the AT group (42.17 ± 7.41 in comparison

  20. Flare Up Reaction During Provocation Test to Glatiramer Acetate in a Patient With Allergy to Interferon Beta1a

    OpenAIRE

    Minciullo, Paola L.; Calapai, Gioacchino; Gangemi, Sebastiano

    2014-01-01

    Glatiramer acetate (GA) is a synthetic amino acid polymer, used for relapsing-remitting multiple sclerosis. The most common adverse effect of GA is a skin reaction at the injection site with a probable IgE-mediated mechanism. We report a case of a 45-year-old woman with multiple sclerosis and urticaria to interferon-β1a, who underwent a challenge test to GA. She presented itching wheals at the intradermal sites. A month later the patient repeated the test and presented the same reactions of t...

  1. Experimental and theoretical studies on the inclusion complexation of syringic acid with alpha-, beta-, gamma- and heptakis(2,6-di-O-methyl)-beta-cyclodextrin.

    Science.gov (United States)

    Song, Le Xin; Wang, Hai Ming; Xu, Peng; Yang, Yan; Zhang, Zi Qiang

    2008-04-01

    Intermolecular interactions of alpha-, beta-, gamma- and heptakis(2,6-di-O-methyl)-beta-cyclodextrin (CD) with syringic acid (Syr) in aqueous solution are investigated by fluorescence spectroscopy. The fluorescence intensity of Syr gradually increases with the addition of the CDs. The formation constants (K) of the host-guest inclusion complexes are determined using a nonlinear analysis. The association abilities of Syr with the CDs decrease in the order gamma->beta->alpha- approximately DMbeta-CD. Both the intrinsic binding abilities of the CDs and the structural effect of Syr are taken into consideration when comparing the K values. Based on the results of NMR experimental and theoretical PM3 calculations both in vacuo and in water, it is found that Syr stays near the wider rim of alpha-CD cavity. Both the number of substituted groups (NSG) in a guest and the molar volume ratio of the guest to host cavity (MVR) play an important role in forming the CD supramolecular complexes of a homologous series of phenol derivatives, such as 2-methoxylphenol (2-Mop), eugenol (Eug) and Syr, i.e., an appropriate NSG or MVR in an inclusion system, such as in 2-Mop-alpha-CD, Eug-beta-CD and Syr-gamma-CD systems, can maximize the intermolecular interaction between host and guest.

  2. High plasma tumor necrosis factor (TNF)-alpha concentrations and a sepsis-like syndrome in patients undergoing hyperthermic isolated limb perfusion with recombinant TNF-alpha, interferon-gamma, and melphalan

    NARCIS (Netherlands)

    Zwaveling, JH; Maring, JK; Clarke, FL; vanGinkel, RJ; Limburg, PC; Hoekstra, HJ; Girbes, ARJ; Schraffordt Koops, H.

    1996-01-01

    Objectives: To describe the postoperative course of patients who underwent hyperthermic isolated limb perfusion with recombinant tumor necrosis factor (TNF)-alpha and melphalan after pretreat ment with recombinant interferon-gamma as treatment for recurrent melanoma, primary nonresectable soft-tissu

  3. A dose escalating, placebo controlled, double blind, single dose and multidose, safety and tolerability study of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe Crohn's disease

    NARCIS (Netherlands)

    W. Reinisch; D.W. Hommes; G. van Assche; J.F. Colombel; J.P. Gendre; B. Oldenburg; A. Teml; K. Geboes; H. Ding; L. Zhang; M. Tang; M. Cheng; S.J.H. van Deventer; P. Rutgeerts; T. Pearce

    2006-01-01

    Introduction: This study was designed to evaluate the safety of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe Crohn's disease (CD). Patients and methods: Forty five patients with a CD activity index (CDAI) of 250 - 450 were randomised in a double blind

  4. Nuclear magnetic resonance spectroscopic study of beta-lactoglobulin interactions with two flavor compounds, gamma-decalactone and beta-ionone.

    Science.gov (United States)

    Lübke, Markus; Guichard, Elisabeth; Tromelin, Anne; Le Quéré, Jean Luc

    2002-11-20

    Interactions between a well-characterized protein, beta-lactoglobulin, and two flavor compounds, beta-ionone and gamma-decalactone, were studied by 2D NMR spectroscopy. NMR spectra were recorded in aqueous solution (pH 2.0, 12 mM NaCl, 10% D(2)O) under conditions such that beta-lactoglobulin is present in a monomeric state. TOCSY and NOESY spectra were recorded on the protein and the complexes between protein and ligands. The spectra of the NH-CH(alpha) region showed the cross-signals due to the coupling between N- and C-bonded protons in the polypeptide backbone. The observed chemical shift variations in the presence of ligands can be assigned to changes in the protein conformation. It appears that the side chains of several amino acids are affected by binding of gamma-decalactone point into the central cavity (Leu46, Ile56, Met107, and Gln120), whereas binding of beta-ionone affects amino acids located in a groove near the outer surface of the protein (Leu104, Tyr120, and Asp129), as illustrated by molecular visualization. This NMR study provides precise information of the location of binding and confirms the existence of two different binding sites for aroma compounds on beta-lactoglobulin, which was suggested in previous competition studies by fluorometry or affinity chromatography and by structural information obtained from infrared spectroscopy. PMID:12428965

  5. 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.

  6. Low immunogenicity but reduced bioavailability of an interferon beta-1a biosimilar compared with its biological parent: results of MATRIX, a cross-sectional, multicenter phase 4 study

    Directory of Open Access Journals (Sweden)

    Cuevas C

    2015-09-01

    Full Text Available Carlos Cuevas,1 Florian Deisenhammer,2 Xiaojun You,3 Mariano Scolnik,4 Regine Buffels,3 Bjørn Sperling,3 Francisco Flores-Ramírez,5 Miguel Macías-Islas,6 Sergio Sauri-Suárez7 On behalf of the MATRIX Investigator Group 1Specialty Hospital, Department of Neurology, National Medical Center Siglo XXI, Mexican Institute of Social Security, Mexico City, Mexico; 2Department of Neurology, University of Innsbruck, Innsbruck, Austria; 3Biogen, Cambridge, MA, USA; 4Biogen, Argentina, Buenos Aires, Argentina; 5Department of Internal Medicine–Neurology, Hospital Regional ISSSTE Monterrey, Monterrey, 6University Center for Health Sciences, University of Guadalajara, Guadalajara, 7Internal Medicine/Department of Neurology, National Medical Center, Mexico City, Mexico Abstract: MATRIX (Measuring neutralizing Antibodies in patients TReated with Interferon beta-1a IM in MeXico was primarily a cross-sectional phase 4 study of patients with relapsing multiple sclerosis (RMS that evaluated neutralizing antibody (NAb frequency in Mexican and Colombian patients treated with intramuscular interferon (IFN beta-1a in the form of Avonex® or the biosimilar drug Jumtab®. A secondary long-term retrospective observational evaluation of safety, tolerability, and relapses was also performed for patients in each arm of the study. In the cross-sectional portion of the study, patients with multiple sclerosis who had been treated with once-weekly Avonex (n=36 or Jumtab (n=29 self-injections as their first and only disease-modifying therapy for 1–3 years were retrospectively identified. The primary and secondary endpoints were proportion of patients with NAb levels >100 tenfold reduction units (TRU and >20 TRU. The biological response to IFN beta-1a injections was assessed by change in serum neopterin levels and by pre- versus post-dose concentration difference. Safety, tolerability, and relapse-related information were also retrospectively assessed. No patients developed

  7. Whole blood interferon-gamma responses to mycobacterium tuberculosis antigens in young household contacts of persons with tuberculosis in Uganda.

    Directory of Open Access Journals (Sweden)

    Deborah A Lewinsohn

    Full Text Available BACKGROUND: Due to immunologic immaturity, IFN-gamma-producing T cell responses may be decreased in young children compared to adults, thus we hypothesized that IFN-gamma responses to mycobacterial antigens in household contacts exposed to Mycobacterium tuberculosis (Mtb would be impaired in young children relative to adults. The objective of this study was to compare whole blood IFN-gamma production in response to mycobacterial antigens between children and adults in Uganda. METHODOLOGY/PRINCIPAL FINDINGS: We studied household contacts of persons with culture-positive pulmonary tuberculosis (TB enrolled in a cohort study conducted in Kampala, Uganda. Whole blood IFN-gamma production in response to Mtb culture-filtrate antigens was measured by ELISA and compared between infants ( or =15 years old, n = 528. We evaluated the relationship between IFN-gamma responses and the tuberculin skin test (TST, and between IFN-gamma responses and epidemiologic factors that reflect exposure to Mtb, and the effect of prior BCG vaccination on IFN-gamma responses. Young household contacts demonstrated robust IFN-gamma responses comparable to those of adults that were associated with TST and known risk factors for infection. There was no effect of prior BCG immunization on the IFN-gamma response. CONCLUSIONS/SIGNIFICANCE: Young children in a TB endemic setting can mount robust IFN-gamma responses generally comparable to those of adults, and as in adults, these responses correlated with the TST and known epidemiologic risk factors for Mtb infection.

  8. Longitudinal study of interferon-gamma, serum antibody and milk antibody responses in cattle infected with Mycobacterium avium subsp paratuberculosis

    DEFF Research Database (Denmark)

    Huda, A.; Jungersen, Gregers; Lind, Peter

    2004-01-01

    cattle of 2+ years of age. Receiver-operating characteristic (ROC) analyses supported the assumption that the IFN-gamma test had a better performance than antibody tests of animals of 1+ and 2+ years of age. However, for animals of 3+ years all tests performed equally well. Application of single sampling......-blood lymphocytes (IFN-gamma test), and measurement of antibody responses against M. paratuberculosis in serum and milk by an in-house absorbed ELISA. The IFN-gamma test diagnosed higher proportions of infected and exposed animals than the antibody ELISAs. The highest sensitivity of IFN-gamma test was in infected...... compared with repeated samplings showed better performance of the IFN-gamma test by repeated samplings, and the milk antibody ELISA in animals of 3+ years of age performed significantly better with repeated sampling compared with single sampling. In conclusion, the IFN-gamma test may be applied...

  9. Assessment of gamma, beta and alpha-particle-emitting nuclides in marine samples

    International Nuclear Information System (INIS)

    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)

  10. Standardization of 18F by Digital beta(LS)-gamma Coincidence Counting

    CERN Document Server

    D., Rodrigues; P., Cassette; P., Arenillas; E., Capoulat M; G., Ceruti; E, García-Toraño

    2010-01-01

    The nuclide 18F disintegrates to 18O by beta+ emission (96.86%) and electron capture (3.14%) with a half-life of 1.8288 h. It is widely used in nuclear medicine for positron emission tomography (PET). Because of its short half-life this nuclide requires the development of fast measuring methods to be standardized. The combination of LSC methods with digital techniques proves to be a good alternative to get low uncertainties for this, and other, short lived nuclides. A radioactive solution of 18F has been standardized by coincidence counting with a LSC, using the logical sum of double coincidences in a TDCR array and a NaI scintillation detector. The results show good consistency with other techniques like 4Pi gamma and LSC.

  11. 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

  12. Neutralizing antibodies to interferon (IFN) alpha-2a and IFN beta-1a or IFN beta-1b in MS are not cross-reactive

    DEFF Research Database (Denmark)

    Myhr, K M; Ross, C; Nyland, H I;

    2000-01-01

    Sera from patients with MS treated with recombinant interferon (rIFN) alpha-2a, rIFNbeta-1a, or rIFNbeta-1b were analyzed for cross-reacting neutralizing antibodies (NAB). Because cross-reactivity was not found, switching treatment from rIFNbeta-1a or rIFNbeta-1b to rIFNalpha-2a might provide...... a secondary treatment response in patients with NAB to rIFNbeta-1a or rIFNbeta-1b. A positive treatment response also might be achieved by switching NAB rIFNalpha-2a-positive patients to rIFNbeta-1a or rIFNbeta-1b....

  13. Peculiarities of the clinical course of radiation sickness and organizational decisions for radiation accidents with beta-gamma sources

    International Nuclear Information System (INIS)

    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)

  14. 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).

  15. 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.

  16. Fabrication of fiber-optic localized surface plasmon resonance sensor and its application to detect antibody-antigen reaction of interferon-gamma

    Science.gov (United States)

    Jeong, Hyeon-Ho; Erdene, Norov; Lee, Seung-Ki; Jeong, Dae-Hong; Park, Jae-Hyoung

    2011-12-01

    A fiber-optic localized surface plasmon (FO LSPR) sensor was fabricated by gold nanoparticles (Au NPs) immobilized on the end-face of an optical fiber. When Au NPs were formed on the end-face of an optical fiber by chemical reaction, Au NPs aggregation occurred and the Au NPs were immobilized in various forms such as monomers, dimers, trimers, etc. The component ratio of the Au NPs on the end-face of the fabricated FO LSPR sensor was slightly changed whenever the sensors were fabricated in the same condition. Including this phenomenon, the FO LSPR sensor was fabricated with high sensitivity by controlling the density of Au NPs. Also, the fabricated sensors were measured for the resonance intensity for the different optical systems and analyzed for the effect on sensitivity. Finally, for application as a biosensor, the sensor was used for detecting the antibody-antigen reaction of interferon-gamma.

  17. Synthesis of fragment 7-20 of human gamma-interferon linked through a methionine residue to polyacrylic resin: use of the adduct as an immunogen.

    Science.gov (United States)

    Mery, J; Hanin, V; Calas, B

    1990-01-01

    A peptide corresponding to the amino acid sequence of human gamma-interferon, residues 7-20, was synthesized by a solid phase procedure using polyacrylic resin and methionine as anchor. Fluorenemethoxycarbonyl and t-butyloxycarbonyl strategies were compared. After completion of the synthesis, side chain deprotections were performed on the peptide still attached to the resin. The purity of the peptide linked to the matrix was determined by amino acid analysis and solid phase sequencing. The presence of methionine allowed the peptide to be detached from the support by CNBr cleavage. The immune responses of the free peptide, the peptide linked to bovine serum albumin and the peptide resin adduct were compared. Peptide bound to polyacrylamide gave similar results to those obtained using classical immunization procedures.

  18. Serum amyloid A-derived peptides, present in human rheumatic synovial fluids, induce the secretion of interferon-gamma by human CD(4)(+) T-lymphocytes.

    Science.gov (United States)

    Yavin, E J; Preciado-Patt, L; Rosen, O; Yaron, M; Suessmuth, R D; Levartowsky, D; Jung, G; Lider, O; Fridkin, M

    2000-04-28

    Serum amyloid A (SAA) is a major acute-phase protein whose biochemical functions remain largely obscure. Human rheumatic synovial fluids were screened by high performance liquid chromatography mass spectrometry for SAA-derived peptides, specifically the sequence AGLPEKY (SAA(98-104)) which was previously shown to modulate various leukocyte functions. Two such fluids were found to contain a truncated version of SAA(98-104). Synthetic SAA(98-104) and several of its analogs were shown capable of binding isolated human CD(4)(+) T-lymphocytes and stimulating them to produce interferon-gamma. Given the high acute-phase serum level of SAA and its massive proteolysis by inflammatory related enzymes, SAA-derived peptides may be involved in host defense mechanisms. PMID:10788622

  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, C.; Nielsen, Søren Saxmose;

    2012-01-01

    Early stage Mycobacterium avium subsp. paratuberculosis (MAP) infection may be detected by measuring antigen specific cell-mediated immune responses by the interferon-gamma (IFN-¿) assay. Available IFN-¿ assay use purified protein derivate of Johnin (PPDj) leading to low specificity. The objectives...... antigens and PPDj. The study included blood samples from 26 heifers of a MAP infected herd, collected three times with 4 and 5 week interval and blood samples from 60 heifers of a MAP noninfected herd collected once. The IFN-¿ responses of the non-infected heifers were used to establish cutoff values...... for each antigen. A case was defined as an animal with =2 positive tests for =4 antigens, resulting in 13 cases and 13 non-cases. Based on the case-definition, immunogenicity and specificity of each antigen were calculated. IFN-¿ levels against each of the antigens of the infected and non-infected herds...

  20. An intermediate gamma beta-beam neutrino experiment with long baseline

    CERN Document Server

    Meloni, Davide; Orme, Christopher; Palomares-Ruiz, Sergio; Pascoli, Silvia

    2008-01-01

    In order to address some fundamental questions in neutrino physics a wide, future programme of neutrino oscillation experiments is currently under discussion. Among those, long baseline experiments will play a crucial role in providing information on the value of theta13, the type of neutrino mass ordering and on the value of the CP-violating phase delta, which enters in 3-neutrino oscillations. Here, we consider a beta-beam setup with an intermediate Lorentz factor gamma=450 and a baseline of 1050 km. This could be achieved in Europe with a beta-beam sourced at CERN to a detector located at the Boulby mine in the United Kingdom. We analyse the physics potential of this setup in detail and study two different exposures (1 x 10^{21} and 5 x 10^{21} ions-kton-years). In both cases, we find that the type of neutrino mass hierarchy could be determined at 99% CL, for all values of delta, for sin^2(2 theta13) > 0.03. In the high-exposure scenario, we find that the value of the CP-violating phase delta could be meas...

  1. 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.

  2. 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)....

  3. Line C17: alpha and medium-level beta-gamma laboratory pilot facility

    Energy Technology Data Exchange (ETDEWEB)

    Calor, J.N.; Mauborgne, B.; Montuir, M. [CEA/VALRHO - site de Marcoule, Dept. de Recherche en Retraitement et en Vitrification (DRRV), 30 - Marcoule (France)

    2000-07-01

    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)

  4. Competition between $\\beta$-delayed proton and $\\beta$-delayed $\\gamma$ decay of the exotic $T_z$ = -2 nucleus $^{56}$Zn and fragmentation of the IAS

    CERN Document Server

    Rubio, B; Fujita, Y; Blank, B; Gelletly, W; Agramunt, J; Algora, A; Ascher, P; Bilgier, B; Cáceres, L; Cakirli, R B; Fujita, H; Ganioglu, E; Gerbaux, M; Giovinazzo, J; Grévy, S; Kamalou, O; Kozer, H C; Kucuk, L; Kurtukian-Nieto, T; Molina, F; Popescu, L; Rogers, A M; Susoy, G; Stodel, C; Suzuki, T; Tamii, A; Thomas, J C

    2015-01-01

    A very exotic decay mode at the proton drip-line, $\\beta$-delayed $\\gamma$-proton decay, has been observed in the $\\beta$ decay of the $T_z$ = -2 nucleus $^{56}$Zn. Three $\\gamma$-proton sequences have been observed following the $\\beta$ decay. The fragmentation of the IAS in $^{56}$Cu has also been observed for the first time. The results were reported in a recent publication. At the time of publication the authors were puzzled by the competition between proton and $\\gamma$ decays from the main component of the IAS. Here we outline a possible explanation based on the nuclear structure properties of the three nuclei involved, namely $^{56}$Zn, $^{56}$Cu and $^{55}$Ni, close to the doubly magic nucleus $^{56}$Ni. From the fragmentation of the Fermi strength and the excitation energy of the two populated 0$^{+}$ states we could deduce the off-diagonal matrix element of the charge-dependent part of the Hamiltonian responsible for the mixing. These results are compared with the decay of $^{55}$Cu with one proton ...

  5. 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

  6. Mutant U5A cells are complemented by an interferon-alpha beta receptor subunit generated by alternative processing of a new member of a cytokine receptor gene cluster.

    Science.gov (United States)

    Lutfalla, G; Holland, S J; Cinato, E; Monneron, D; Reboul, J; Rogers, N C; Smith, J M; Stark, G R; Gardiner, K; Mogensen, K E

    1995-10-16

    The cellular receptor for the alpha/beta interferons contains at least two components that interact with interferon. The ifnar1 component is well characterized and a putative ifnar2 cDNA has recently been identified. We have cloned the gene for ifnar2 and show that it produces four different transcripts encoding three different polypeptides that are generated by exon skipping, alternative splicing and differential use of polyadenylation sites. One polypeptide is likely to be secreted and two are transmembrane proteins with identical extracellular and transmembrane domains but divergent cytoplasmic tails of 67 and 251 amino acids. A mutant cell line U5A, completely defective in IFN-alpha beta binding and response, has been isolated and characterized. Expression in U5A cells of the polypeptide with the long cytoplasmic domain reconstitutes a functional receptor that restores normal interferon binding, activation of the JAK/STAT signal transduction pathway, interferon-inducible gene expression and antiviral response. The IFNAR2 gene maps at 0.5 kb from the CRFB4 gene, establishing that together IFNAR2, CRFB4, IFNAR1 and AF1 form a cluster of class II cytokine receptor genes on human chromosome 21.

  7. 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

  8. Assessment of malignancy risk in patients with multiple sclerosis treated with intramuscular interferon beta-1a: retrospective evaluation using a health insurance claims database and postmarketing surveillance data

    Directory of Open Access Journals (Sweden)

    Bloomgren G

    2012-06-01

    Full Text Available Gary Bloomgren, Bjørn Sperling, Kimberly Cushing, Madé WentenBiogen Idec Inc., Weston, MA, USABackground: Intramuscular interferon beta-1a (IFNβ-1a, a multiple sclerosis (MS therapy that has been commercially available for over a decade, provides a unique opportunity to retrospectively assess postmarketing data for evidence of malignancy risk, compared with relatively limited data available for more recently approved therapies. Postmarketing and claims data were analyzed to determine the risk of malignancy in MS patients treated with intramuscular IFNβ-1a.Materials and methods: The cumulative reporting rates of suspected adverse drug reactions coded to malignancy in the intramuscular IFNβ-1a global safety database were compared with malignancy incidence rates in the World Health Organization GLOBOCAN database. In addition, using data from a large US claims database, the cumulative prevalence of malignancy in MS patients treated with intramuscular IFNβ-1a was compared with non-MS population controls, MS patients without intramuscular IFNβ-1a use, and untreated MS patients. Mean follow-up was approximately 3 years for all groups, ie, 3.1 years for the intramuscular IFNβ-1a group (range 0.02–6.0 years, 2.6 years for non-MS population controls (range 0–6.0 years, 2.6 years for the intramuscular IFNβ-1a nonuse group (range 0.01–6.0 years, and 2.4 years for the untreated MS group (range 0.01–6.0 years.Results: An estimated 402,250 patients received intramuscular IFNβ-1a during the postmarketing period. Cumulative reporting rates of malignancy in this population were consistent with GLOBOCAN incidence rates observed within the general population. The claims database included 12,894 MS patients who received intramuscular IFNβ-1a. No significant difference in malignancy prevalence was observed in intramuscular IFNβ-1a users compared with other groups.Conclusion: Results from this evaluation provide no evidence of an increased risk of

  9. Upregulation of SOCS-3 and PIAS-3 impairs IL-12-mediated interferon-gamma response in CD56 T cells in HCV-infected heroin users.

    Directory of Open Access Journals (Sweden)

    Li Ye

    Full Text Available BACKGROUND: CD56(+ T cells are abundant in liver and play an important role in host innate immunity against viral infections, including hepatitis C virus (HCV infection, a common infection among heroin abusers. We thus investigated the in vivo impact of heroin use or heroin use plus HCV infection on the CD56(+ T cell frequency and function. METHODOLOGY/PRINCIPAL FINDINGS: A total of 37 heroin users with (17 or without (20 HCV infection and 17 healthy subjects were included in the study. Although there was no significant difference in CD56(+ T cell frequency in PBMCs among three study groups, CD56(+ T cells isolated from the heroin users had significantly lower levels of constitutive interferon-gamma (IFN-gamma expression than those from the normal subjects. In addition, when stimulated by interleukin (IL-12, CD56(+ natural T cells from HCV-infected heroin users produced significantly lower levels of IFN-gamma than those from the normal subjects. This diminished ability to produce IFN-gamma by CD56(+ T cells was associated with the increased plasma HCV viral loads in the HCV-infected heroin users. Investigation of the mechanisms showed that although heroin use or heroin use plus HCV infection had little impact on the expression of the key positive regulators (IL-12 receptors, STAT-1, 3, 4, 5, JAK-2, and TYK-2 in IL-12 pathway, heroin use or heroin use plus HCV infection induced the expression of suppressor of cytokine signaling protein-3 (SOCS-3 and protein inhibitors of activated STAT-3 (PIAS-3, two key inhibitors of IL-12 pathway. CONCLUSION/SIGNIFICANCE: These findings provide compelling in vivo evidence that heroin use or heroin use plus HCV infection impairs CD56(+ T cell-mediated innate immune function, which may account for HCV infection and persistence in liver.

  10. Histone deacetylase 1/mSin3A disrupts gamma interferon-induced CIITA function and major histocompatibility complex class II enhanceosome formation.

    Science.gov (United States)

    Zika, Eleni; Greer, Susanna F; Zhu, Xin-Sheng; Ting, Jenny P-Y

    2003-05-01

    The class II transactivator (CIITA) is a master transcriptional regulator of major histocompatibility complex class II (MHC-II) promoters. CIITA does not bind DNA, but it interacts with the transcription factors RFX5, NF-Y, and CREB and associated chromatin-modifying enzymes to form an enhanceosome. This report examines the effects of histone deacetylases 1 and 2 (HDAC1/HDAC2) on MHC-II gene induction by gamma interferon (IFN-gamma) and CIITA. The results show that an inhibitor of HDACs, trichostatin A, enhances IFN-gamma-induced MHC-II expression, while HDAC1/HDAC2 inhibits IFN-gamma- and CIITA-induced MHC-II gene expression. mSin3A, a corepressor of HDAC1/HDAC2, is important for this inhibition, while NcoR, a corepressor of HDAC3, is not. The effect of this inhibition is directed at CIITA, since HDAC1/HDAC2 reduces transactivation by a GAL4-CIITA fusion protein. CIITA binds to overexpressed and endogenous HDAC1, suggesting that HDAC and CIITA may affect each other by direct or indirect association. Inhibition of HDAC activity dramatically increases the association of NF-YB and RFX5 with CIITA, the assembly of CIITA, NF-YB, and RFX5 enhanceosome, and the extent of H3 acetylation at the MHC-II promoter. These results suggest a model where HDAC1/HDAC2 affect the function of CIITA through a disruption of MHC-II enhanceosome and relevant coactivator-transcription factor association and provide evidence that CIITA may act as a molecular switch to modulate MHC-II transcription by coordinating the functions of both histone acetylases and HDACs.

  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. Optimization of a high-throughput whole blood expression profiling methodology and its application to assess the pharmacodynamics of interferon (IFN beta-1a or polyethylene glycol-conjugated IFN beta-1a in healthy clinical trial subjects

    Directory of Open Access Journals (Sweden)

    Allaire Normand E

    2013-01-01

    Full Text Available Abstract Background Clinical trials offer a unique opportunity to study human disease and response to therapy in a highly controlled setting. The application of high-throughput expression profiling to peripheral blood from clinical trial subjects could facilitate the identification of transcripts that function as prognostic or diagnostic markers of disease or treatment. The paramount issue for these methods is the ability to produce robust, reproducible, and timely mRNA expression profiles from peripheral blood. Single-stranded complementary DNA (sscDNA targets derived from whole blood exhibit improved detection of transcripts and reduced variance as compared to their complementary RNA counterparts and therefore provide a better option for interrogation of peripheral blood on oligonucleotide arrays. High-throughput microarray technologies such as the high-throughput plate array platform offer several advantages compared with slide- or cartridge-based arrays; however, manufacturer’s protocols do not support the use of sscDNA targets. Results We have developed a highly reproducible, high-through put, whole blood expression profiling methodology based on sscDNA and used it to analyze human brain reference RNA and universal human reference RNA samples to identify experimental conditions that most highly correlated with a gold standard quantitative polymerase chain reaction reference dataset. We then utilized the optimized method to analyze whole blood samples from healthy clinical trial subjects treated with different versions of interferon (IFN beta-1a. Analysis of whole blood samples before and after treatment with intramuscular [IM] IFN beta-1a or polyethylene glycol-conjugated IFN (PEG-IFN beta-1a under optimized experimental conditions demonstrated that PEG-IFN beta-1a induced a more sustained and prolonged pharmacodynamic response than unmodified IM IFN beta-1a. These results provide validation of the utility of this new methodology and

  13. Analysis of beta, gamma, and delta T-cell receptor genes in mycosis fungoides and Sezary syndrome.

    Science.gov (United States)

    Whittaker, S J; Smith, N P; Jones, R R; Luzzatto, L

    1991-10-01

    The authors have analyzed the configuration of immunoglobulin (Ig) and beta, gamma and delta T-cell receptor (TCR) genes in DNA extracted from skin, lymph nodes, and peripheral blood mononuclear cells obtained from 41 patients with mycosis fungoides (MF), 14 patients with Sezary syndrome, and 13 patients with benign inflammatory dermatoses. No discrete rearranged bands (DRB) were detected in patients with inflammatory dermatoses. In tissue DNA from 19 patients with MF DRB were detected with beta and gamma, but not delta TCR probes. Only one patient with MF had a rearrangement of gamma and delta with germ line beta TCR genes. In 13 patients multiple biopsies were analyzed and DRB, when present, were identical in different lesions from individual patients. In three patients analysis of DNA from dermatopathic lymph nodes did not reveal DRB. Analysis of peripheral blood DNA from 24 patients revealed a discrete rearrangement of the gamma TCR gene in four patients and both beta and gamma genes in four additional patients. In MF DRB were detected more frequently with advancing stage of disease in tissues (P less than 0.01) but not in peripheral blood (P equals 0.36). Of 14 patients with Sezary syndrome, eight had DRB in peripheral blood DNA with both beta and gamma probes and in three of these patients identical DRB were also detected in DNA from skin biopsy samples. In contrast, DRB were not detected in the peripheral blood of the other six patients. In both MF and Sezary syndrome there was no restricted usage of particular V gamma genes. These results indicate that in MF (1) T-cell clones can be detected in skin biopsy specimens from the majority of patients with early stage disease, (2) gamma delta T-cell clones are only rarely found, and (3) TCR gene analysis can detect T-cell clones in the peripheral blood with a greater degree of specificity than conventional light microscopic study. In Sezary syndrome these studies also suggest that a subset of patients have a

  14. Total Absorption Gamma-Ray Spectroscopy of 87Br, 88Br and 94Rb Beta-Delayed Neutron Emitters

    CERN Document Server

    Valencia, E; Algora, A; Agramunt, J; Rubio, B; Rice, S; Gelletly, W; Regan, P; Zakari-Issoufou, A -A; Fallot, M; Porta, A; Rissanen, J; Eronen, T; Aysto, J; Batist, L; Bowry, M; Bui, V M; Caballero-Folch, R; Cano-Ott, D; Elomaa, V -V; Estevez, E; Farrelly, G F; Garcia, A R; Gomez-Hornillos, B; Gorlychev, V; Hakala, J; Jordan, M D; Jokinen, A; Kolhinen, V S; Kondev, F G; Martinez, T; Mendoza, E; Moore, I; Penttila, H; Podolyak, Zs; Reponen, M; Sonnenschein, V; Sonzogni, A A

    2016-01-01

    We investigate the decay of 87Br, 88Br and 94Rb using total absorption gamma-ray spectroscopy. These important fission products are beta-delayed neutron emitters. Our data show considerable gamma-intensity, so far unobserved in high-resolution gamma-ray spectroscopy, from states at high excitation energy. We also find significant differences with the beta intensity that can be deduced from existing measurements of the beta spectrum. We evaluate the impact of the present data on reactor decay heat using summation calculations. Although the effect is relatively small it helps to reduce the discrepancy between calculations and integral measurements of the photon component for 235U fission at cooling times in the range 1 to 100 s. We also use summation calculations to evaluate the impact of present data on reactor antineutrino spectra. We find a significant effect at antineutrino energies in the range of 5 to 9 MeV. In addition, we observe an unexpected strong probability for gamma emission from neutron unbound s...

  15. 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...... 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...... and subsequently enhanced by the ability of IFN-gamma to induce de novo MHC class II expression in the colonic epithelium, a change which could lead to increased antigen processing and production of local proinflammatory cytokines, CD4+ T cell turnover and thereby to exaggeration of disease....

  16. Analysis of repeated tests for interferon-gamma (IFN-gamma) response and faecal excretion for diagnosis of subclinical paratuberculosis in Danish cattle

    DEFF Research Database (Denmark)

    Huda, A.; Lind, Peter; Christoffersen, Anna-Bodil;

    2003-01-01

    -positive cattle tested positive at least once in the IFN-gamma test. It was not possible to predict from the IFN-gamma test result the number of animals that would eventually develop disease. However, the test may be useful to detect animals that have been exposed to M. paratuberculosis earlier in their lives...... (48%) were positive in the IFN-gamma test on at least one sampling using "IDEXX-criteria" for interpretation, and of I 10 cattle from five non-infected herds three (3%) were positive. Forty-four animals from infected and one from non-infected herds tested positive at all three samplings. Although...... support for the specificity of the IFN-gamma test was provided by these results, they also indicate. problems with false positives. Approximately half of the positive animals did not give the same result at all three samplings, indicating that repeated testing increases the chance of detecting reactors...

  17. A Population Approach to Characterize Interferon Beta-1b Effect on Contrast Enhancing Lesions in Patients With Relapsing Remitting Multiple Sclerosis.

    Science.gov (United States)

    Gulati, A; Bagnato, F; Villoslada, P; Velez de Mendizabal, N

    2015-05-01

    In patients with relapsing-remitting multiple sclerosis (RRMS), interferon beta-1b (IFNβ-1b) reduces the occurrence of contrast enhancing lesions (CELs) on magnetic resonance imaging (MRI). Questions remain on the stability of IFNβ-1b effect over time and its action beyond the reduction of CELs. In this study, we described the IFNβ-1b effect by a mixed effects model, quantifying the interpatient variability associated with its parameters. Using a negative binomial distribution model as a natural history model, the effect of IFNβ-1b was evaluated using different mathematical functions of time. IFNβ-1b produced a decrease in the expected CEL numbers, inhibiting the formation of new CELs but did not promote the resolution of the already-formed ones. Based on the final selected model, simulations were carried out to optimize the combined IFNβ-1b-corticosteroid therapy as a proof-of-concept. In summary, we provide evidence on the dynamics of CELs under IFNβ-1b treatment that can be used to monitor the effects of therapies in MS. PMID:26225255

  18. Contribution of the gamma-carboxyl group of Glu-43(beta) to the alkaline Bohr effect of hemoglobin A.

    Science.gov (United States)

    Rao, M J; Acharya, A S

    1992-08-18

    Glu-43(beta) of hemoglobin A exhibits a high degree of chemical reactivity around neutral pH for amidation with nucleophiles in the presence of carbodiimide. Such a reactivity is unusual for the side-chain carboxyl groups of proteins. In addition, the reactivity of Glu-43(beta) is also sensitive to the ligation state of the protein [Rao, M. J., & Acharya, A. S. (1991) J. Protein Chem. 10, 129-138]. The influence of deoxygenation of hemoglobin A on the chemical reactivity of the gamma-carboxyl group of Glu-43(beta) has now been investigated as a function of pH (from 5.5 to 7.5). The chemical reactivity of Glu-43(beta) for amidation increases upon deoxygenation only when the modification reaction is carried out above pH 6.0. The pH-chemical reactivity profile of the amidation of hemoglobin A in the deoxy conformation reflects an apparent pKa of 7.0 for the gamma-carboxyl group of Glu-43(beta). This pKa is considerably higher than the pKa of 6.35 for the oxy conformation. The deoxy conformational transition mediated increase in the pKa of the gamma-carboxyl group of Glu-43(beta) implicates this carboxyl group as an alkaline Bohr group. The amidated derivative of hemoglobin A with 2 mol of glycine ethyl ester covalently bound to the protein was isolated by CM-cellulose chromatography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1354984

  19. Structural basis for distinctive recognition of fibrinogen [gamma]C peptide by the platelet integrin [alpha][subscript IIb][beta]3

    Energy Technology Data Exchange (ETDEWEB)

    Springer, Timothy A.; Zhu, Jianghai; Xiao, Tsan (Harvard-Med)

    2009-01-12

    Hemostasis and thrombosis (blood clotting) involve fibrinogen binding to integrin {alpha}{sub IIb}{beta}{sub 3} on platelets, resulting in platelet aggregation. {alpha}{sub v}{beta}{sub 3} binding fibrinogen via an Arg-Asp-Gly (RGD) motif in fibrinogen's {alpha} subunit. {alpha}{sub IIb}{beta}{sub 3} also binds to fibrinogen; however, it does so via an unstructured RGD-lacking C-terminal region of the {gamma} subunit ({gamma}C peptide). These distinct modes of fibrinogen binding enable {alpha}{sub IIb}{beta}{sub 3} and {alpha}{sub v}{beta}{sub 3} to function cooperatively in hemostasis. In this study, crystal structures reveal the integrin {alpha}{sub IIb}{beta}{sub 3}-{gamma}C peptide interface, and, for comparison, integrin {alpha}{sub IIb}{beta}{sub 3} bound to a lamprey {gamma}C primordial RGD motif. Compared with RGD, the GAKQAGDV motif in {gamma}C adopts a different backbone configuration and binds over a more extended region. The integrin metal ion-dependent adhesion site (MIDAS) Mg{sup 2+} ion binds the {gamma}C Asp side chain. The adjacent to MIDAS (ADMIDAS) Ca{sup 2+} ion binds the {gamma}C C terminus, revealing a contribution for ADMIDAS in ligand binding. Structural data from this natively disordered {gamma}C peptide enhances our understanding of the involvement of {gamma}C peptide and integrin {alpha}{sub IIb}{beta}{sub 3} in hemostasis and thrombosis.

  20. Serum concentrations of sIL-2R, IL-6, TGF-beta1, neopterin, and zinc in chronic hepatitis C patients treated with interferon-alpha.

    Science.gov (United States)

    Grüngreiff, K; Reinhold, D; Ansorge, S

    1999-12-01

    T lymphocytes and immunoregulatory cytokines play an important role in the host response to hepatitis C virus (HCV) infection. Zinc is required for a wide spectrum of immune functions, including T-cell activity. To determine the clinical significance of the cytokines sIL-2R, IL-6, TGF-beta1, neopterin, and of zinc in chronic heptatitis C virus (HCV) infection, we investigated their concentrations in the serum of 16 patients with chronic HCV infection before, during and at the end of therapy with interferon (IFN) alpha (Roferon A), and after 6 months follow-up. Elevated concentrations of sIL-2R, IL-6, TGF-beta1, and neopterin were found in the serum of all patients prior to therapy, as compared to healthy controls. sIL-2R patterns differed in responders and non-responders. While the mean concentration of sIL-2R (335.75 pg/ml) before therapy was about 40% higher in complete responders (n=4) than in controls (272.20 pg/ml), the mean concentration in non-responders (n=6) was 4-fold higher than in controls (1153.33 pg/ml). During therapy, sIL-2R levels in responders decreased by about 40%. Mean IL-6 concentrations in both complete and partial responders (n=6) decreased continuously during treatment, while mean concentrations in non-responders decreased for only a short time, and increased again after cessation of therapy. Mean levels of TGF-beta1 behaved similarly to those of IL-6. Only negligible differences in mean neopterin levels were found between responders and non-responders over the entire observation time. The mean serum zinc concentrations slightly decreased in all 3 patient groups, the greatest reduction occurring in 3 of the 4 responders. The present findings underscore the importance of the immune system in the pathogenesis of chronic HCV infection. Serum sIL-2R levels may be used as a serological marker of outcome following IFN-alpha treatment. PMID:10623433

  1. Delayed translational silencing of ceruloplasmin transcript in gamma interferon-activated U937 monocytic cells: role of the 3' untranslated region

    Science.gov (United States)

    Mazumder, B.; Fox, P. L.

    1999-01-01

    Ceruloplasmin (Cp) is an acute-phase protein with ferroxidase, amine oxidase, and pro- and antioxidant activities. The primary site of Cp synthesis in human adults is the liver, but it is also synthesized by cells of monocytic origin. We have shown that gamma interferon (IFN-gamma) induces the synthesis of Cp mRNA and protein in monocytic cells. We now report that the induced synthesis of Cp is terminated by a mechanism involving transcript-specific translational repression. Cp protein synthesis in U937 cells ceased after 16 h even in the presence of abundant Cp mRNA. RNA isolated from cells treated with IFN-gamma for 24 h exhibited a high in vitro translation rate, suggesting that the transcript was not defective. Ribosomal association of Cp mRNA was examined by sucrose centrifugation. When Cp synthesis was high, i.e., after 8 h of IFN-gamma treatment, Cp mRNA was primarily associated with polyribosomes. However, after 24 h, when Cp synthesis was low, Cp mRNA was primarily in the nonpolyribosomal fraction. Cytosolic extracts from cells treated with IFN-gamma for 24 h, but not for 8 h, contained a factor which blocked in vitro Cp translation. Inhibitor expression was cell type specific and present in extracts of human cells of myeloid origin, but not in several nonmyeloid cells. The inhibitory factor bound to the 3' untranslated region (3'-UTR) of Cp mRNA, as shown by restoration of in vitro translation by synthetic 3'-UTR added as a "decoy" and detection of a binding complex by RNA gel shift analysis. Deletion mapping of the Cp 3'-UTR indicated an internal 100-nucleotide region of the Cp 3'-UTR that was required for complex formation as well as for silencing of translation. Although transcript-specific translational control is common during development and differentiation and global translational control occurs during responses to cytokines and stress, to our knowledge, this is the first report of translational silencing of a specific transcript following cytokine

  2. Alpha-amino acid behaves differently from beta- or gamma-amino acids as treated by trimetaphosphate.

    Science.gov (United States)

    Gao, X; Liu, Y; Xu, P X; Cai, Y M; Zhao, Y F

    2008-01-01

    The condensation reactions of sodium trimetaphosphate with single amino acids, namely glycine, L-alanine, beta-alanine and gamma-aminobutyric acid or pairs of these amino acids were reinvestigated by electrospray ion-trap mass spectrometry and high performance liquid chromatography. It was found when mixtures were treated by sodium trimetaphosphate only in the presence of alpha-amino acid dipeptides were formed. Without addition of alpha-amino acids, the beta-amino acid or gamma-aminobutyric acid could not form peptide either by themselves or with their mixtures under the same conditions. From the data it is concluded that phosphate might select alpha-amino acids to produce the peptides being important precursors for the origin of life. PMID:17973074

  3. 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.

  4. A new approach to beta-gamma coincidence counting. Advance report on the Samar electronic system

    International Nuclear Information System (INIS)

    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

  5. Induction of indoleamine 2,3-dioxygenase in vascular smooth muscle cells by interferon-gamma contributes to medial immunoprivilege.

    Science.gov (United States)

    Cuffy, Madison C; Silverio, Amanda M; Qin, Lingfeng; Wang, Yinong; Eid, Raymond; Brandacher, Gerald; Lakkis, Fadi G; Fuchs, Dietmar; Pober, Jordan S; Tellides, George

    2007-10-15

    Atherosclerosis and graft arteriosclerosis are characterized by leukocytic infiltration of the vessel wall that spares the media. The mechanism(s) for medial immunoprivilege is unknown. In a chimeric humanized mouse model of allograft rejection, medial immunoprivilege was associated with expression of IDO by vascular smooth muscle cells (VSMCs) of rejecting human coronary artery grafts. Inhibition of IDO by 1-methyl-tryptophan (1-MT) increased medial infiltration by allogeneic T cells and increased VSMC loss. IFN-gamma-induced IDO expression and activity in cultured human VSMCs was considerably greater than in endothelial cells (ECs) or T cells. IFN-gamma-treated VSMCs, but not untreated VSMCs nor ECs with or without IFN-gamma pretreatment, inhibited memory Th cell alloresponses across a semipermeable membrane in vitro. This effect was reversed by 1-MT treatment or tryptophan supplementation and replicated by the absence of tryptophan, but not by addition of tryptophan metabolites. However, IFN-gamma-treated VSMCs did not activate allogeneic memory Th cells, even after addition of 1-MT or tryptophan. Our work extends the concept of medial immunoprivilege to include immune regulation, establishes the compartmentalization of immune responses within the vessel wall due to distinct microenvironments, and demonstrates a duality of stimulatory EC signals versus inhibitory VSMC signals to artery-infiltrating T cells that may contribute to the chronicity of arteriosclerotic diseases.

  6. 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

  7. Proton and $\\gamma$- partial widths of astrophysically important states of $^{30}$S studied by the $\\beta$-delayed decay of $^{31}$Ar

    CERN Document Server

    Koldste, G T; Borge, M J G; Briz, J A; Carmona-Gallardo, M; Fraile, L M; Fynbo, H O U; Giovinazzo, J; Johansen, J G; Jokinen, A; Jonson, B; Kurturkian-Nieto, T; Kusk, J H; Nilsson, T; Perea, A; Pesudo, V; Picado, E; Riisager, K; Saastamoinen, A; Tengblad, O; Thomas, J -C; Van de Walle, J

    2013-01-01

    Resonances just above the proton threshold in $^{30}$S affect the $^{29}$P(p,$\\gamma$)$^{30}$S reaction under astrophysical conditions. The (p,$\\gamma$)-reaction rate is currently determined indirectly and depends on the properties of the relevant resonances. We present here a method for finding the ratio between the proton and $\\gamma$- partial widths of resonances in $^{30}$S. The widths are determined from the $\\beta$-2p and $\\beta$-p-$\\gamma$- decay of $^{31}$Ar, which is produced at ISOLDE, CERN. Experimental limits on the ratio between the proton and $\\gamma$- partial widths for astrophysical relevant levels in $^{30}$S have been found for the first time. A level at 4689.2(24)keV is identified in the $\\gamma$-spectrum, and an upper limit on the $\\Gamma_{p}/\\Gamma_{\\gamma}$ ratio of 0.26 (95% C.L.) is found. In the two-proton spectrum two levels at 5227(3)keV and 5847(4)keV are identified. These levels were previously seen to $\\gamma$-decay and upper limits on the $\\Gamma_{\\gamma}/\\Gamma_{p}$ ratio of 0....

  8. 4{\\pi}{\\beta} (LS)-{\\gamma} (HPGe) Digital Coincidence System Based on Synchronous High-Speed Multichannel Data Acquisition

    CERN Document Server

    Chen, Jifeng; Liang, Juncheng; Liu, Jiacheng

    2015-01-01

    A dedicated 4{\\pi}{\\beta} (LS)-{\\gamma} (HPGe)digital coincidence system has been developed in this work, which includes five acquisition channels. Three analog-to-digital converter (ADC) acquisition channels with an acquisition resolution of 8 bits and acquisition rate of 1GSPS (sample per second) are utilized to collect the signals from three Photo multiplier tubes (PMTs) which are adopted to detect {\\beta} decay, and two acquisition channels with an acquisition resolution of 16 bits and acquisition rate of 50MSPS are utilized to collect the signals from high-purity germanium (HPGe) which are adopted to detect {\\gamma} decay. In order to increase the accuracy of the coincidence system, all the five acquisition channels are synchronous within 500ps. The data collected by the five acquisition channels will be transmitted to the host PC through PCI bus and saved as a file. Off-line software is applied for the 4{\\pi}{\\beta} (LS)-{\\gamma} (HPGe) coincidence and data analysis as needed in practical application. W...

  9. Two distinct olfactory bulb sublaminar networks involved in gamma and beta oscillation generation: a CSD study in the anesthetized rat.

    Directory of Open Access Journals (Sweden)

    Nicolas eFourcaud-Trocmé

    2014-07-01

    Full Text Available A prominent feature of olfactory bulb (OB dynamics is the expression of characteristic local field potential (LFP rhythms, including a slow respiration-related rhythm and two fast alternating oscillatory rhythms, beta (15-30 Hz and gamma (40-90 Hz. All of these rhythms are implicated in olfactory coding. Fast oscillatory rhythms are known to involve the mitral-granule cell loops. Although the underlying mechanisms of gamma oscillation have been studied, the origin of beta oscillation remains poorly understood. Whether these two different rhythms share the same underlying mechanism is unknown. This study uses a quantitative and detailed current-source density analysis combined with multi-unit activity recordings to shed light on this question in freely breathing anesthetized rats. In particular, we show that gamma oscillation generation involves mainly upper half of the external plexiform layer (EPL and superficial areas of granule cell layer. In contrast, the generation of beta oscillation involves the lower part of the EPL and deep granule cells. This differential involvement of sublaminar networks is neither dependent on odor quality nor on the precise frequency of the fast oscillation under study. Overall, this study demonstrates a functional sublaminar organization of the rat OB, which is supported by previous anatomical findings.

  10. Serum concentrations of the interferon-gamma-inducible chemokine IP-10/CXCL10 are augmented in both newly diagnosed Type I diabetes mellitus patients and subjects at risk of developing the disease

    DEFF Research Database (Denmark)

    Nicoletti, F; Conget, I; Di Mauro, M;

    2002-01-01

    Chemokines are chemotactic cytokines controlling the recruitment of leukocytes from the blood by regulating integrin adhesiveness. It has been shown that the migration of CD4+Th1 and CD4+Th2 cells is governed by specific chemokines. Increasing evidence suggests that the CD4+Th1 cheomoattractant c...... chemokine CXCL10, also termed Interferon (IFN)-gamma -inducible protein (IP)-10 is pathogenetically involved in several immunoinflammatory and autoimmune diseases....

  11. The effectiveness of asthma therapy alternatives and evaluating the effectivity of asthma therapy by interleukin-13 and interferon gamma levels in children.

    Science.gov (United States)

    Karaman, Ozkan; Arli, Ozgun; Uzuner, Nevin; Islekel, Huray; Babayigit, Arzu; Olmez, Duygu; Kose, Suna; Tezcan, Dilek

    2007-01-01

    This study evaluated the superiority of combination therapy over steroid therapy alone by using clinical and laboratory data including interleukin (IL)-13 and interferon (IFN) gamma, which participate in the characteristic inflammation and have not been studied to evaluate the efficiency of asthma treatment sufficiently. Moderate persistent asthma patients, aged 7-17 years were included in the study. Patients were randomized to three groups. Group 1 used inhaled budesonide, group 2 used inhaled budesonide plus inhaled formoterol fumarate, and group 3 used inhaled budesonide and oral montelukast sodium therapy. At the beginning and at the end of the 2nd month a detailed physical examination and clinical evaluation; total IgE levels and total eosinophil count in peripheral venous blood, serum IL-13, and IFN-gamma levels; pulmonary function tests; and an assessment questionnaire (Pediatric Asthma Quality-of-Life Questionnaire with Standardized Activities [PAQLQ{S}] were performed. Sixty-seven patients completed the study. Serum IL-13 levels and PAQLQ(S) scores before the therapy and serum IL-13 levels after the therapy were significantly different between the groups and other parameters did not show any significant differences. Serum IgE level was decreased after the therapy in group I and increased in groups 2 and 3, but the difference was insignificant. In all groups total eosinophil levels were decreased insignificantly. After the therapy, IL-13 levels were decreased in groups 1 and 2 and increased in group 3, but the difference was not statistically significant. When compared with the levels before the therapy IFN-gamma levels were decreased after the therapy but the difference was not statistically significant. When the improvement rates for IgE, total eosinophil, IL-13, and IFN-gamma levels and each parameter of respiratory function tests were compared, there were no significant differences between the therapy groups. In all groups PAQLQ(S) scores were

  12. Phase I trial with recombinant interleukin-2 (rIL-2): immune activation by rIL-2 alone or following pretreatment with recombinant interferon-gamma.

    Science.gov (United States)

    Farace, F; Mathiot, C; Brandely, M; Tursz, T; Dorval, T; Pouillart, P; Triebel, F; Hercend, T; Fridman, W H

    1990-01-01

    Alterations of immunological parameters were analysed in patients with advanced malignancies during a phase I trial with rIL-2. Five-day infusions of rIL-2 at doses from 1 x 10(6) to 24 x 10(6) biological response modifiers program (BRMP) U/m2 per day were given to 29 patients, with a minimum of three patients per dose. The dose of 24 x 10(6) U/m2 per day was the maximal tolerated dose (MTD). Immunological parameters were analyzed at days 0, 8 and 11 of the rIL-2 courses. Following a leucopenia during rIL-2 infusion, a lymphocytosis was found in all patients except one. The lymphocytosis peaked at day 8 and was detected at doses of rIL-2 as low as 1 x 10(6) U/m2 per day, reaching a plateau at a dose of 16 x 10(6) U/m2 per day. Although all lymphocyte subsets were increased in patients receiving rIL-2, some patients had predominant T cells (CD3+, NKH1(CD56)-), others had predominant natural killer (NK) cells (CD3-, NKH1 (CD56)+), and yet others showed a mixed profile. A strong induction of cells cytotoxic for K562 targets was found in all patients at days 8 and 11. Eighteen patients received, 1 month later, a second treatment in which infusion of rIL-2 was preceded by a course of 5 days infusion of 2 x 10(6) U/m2 per day recombinant interferon-gamma (rIFN-gamma). The infusion of rIFN-gamma prior to rIL-2 had no effect on the rIL-2-induced alterations of immunological parameters. Taken together, our results suggest that immune stimulation by rIL-2 occurs even at low doses and is maximal at a dose below the MTD; and that pretreatment with low-dose rIFN-gamma does not modify the immune stimulation by rIL-2. PMID:2122928

  13. 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.

  14. Polygonum cuspidatum and its active components inhibit replication of the influenza virus through toll-like receptor 9-induced interferon beta expression.

    Directory of Open Access Journals (Sweden)

    Chao-Jen Lin

    Full Text Available Influenza virus infection is a global public health issue. The effectiveness of antiviral therapies for influenza has been limited by the emergence of drug-resistant viral strains. Therefore, there is an urgent need to identify novel antiviral therapies. Here we tested the effects of 300 traditional Chinese medicines on the replication of various influenza virus strains in a lung cell line, A549, using an influenza-specific luciferase reporter assay. Of the traditional medicines tested, Polygonum cuspidatum (PC and its active components, resveratrol and emodin, were found to attenuate influenza viral replication in A549 cells. Furthermore, they preferentially inhibited the replication of influenza A virus, including clinical strains isolated in 2009 and 2011 in Taiwan and the laboratory strain A/WSN/33 (H1N1. In addition to inhibiting the expression of hemagglutinin and neuraminidase, PC, emodin, and resveratrol also increased the expression of interferon beta (IFN-β through Toll-like receptor 9 (TLR9. Moreover, the anti-viral activity of IFN-β or resveratrol was reduced when the A549 cells were treated with neutralizing anti-IFN-β antibodies or a TLR9 inhibitor, suggesting that IFN-β likely acts synergistically with resveratrol to inhibit H1N1 replication. This potential antiviral mechanism, involving direct inhibition of virus replication and simultaneous activation of the host immune response, has not been previously described for a single antiviral molecule. In conclusion, our data support the use of PC, resveratrol or emodin for inhibiting influenza virus replication directly and via TLR-9-induced IFN-β production.

  15. Synergistic effect of therapeutic stem cells expressing cytosine deaminase and interferon-beta via apoptotic pathway in the metastatic mouse model of breast cancer.

    Science.gov (United States)

    Yi, Bo-Rim; Kim, Seung U; Choi, Kyung-Chul

    2016-02-01

    As an approach to improve treatment of breast cancer metastasis to the brain, we employed genetically engineered stem cells (GESTECs, HB1.F3 cells) consisting of neural stem cells (NSCs) expressing cytosine deaminase and the interferon-beta genes, HB1.F3.CD and HB1.F3.CD.IFN-β. In this model, MDA-MB-231/Luc breast cancer cells were implanted in the right hemisphere of the mouse brain, while pre-stained GESTECs with redfluorescence were implanted in the contralateral brain. Two days after stem cells injection, 5-fluorocytosine (5-FC) was administrated via intraperitoneal injection. Histological analysis of extracted brain confirmed the therapeutic efficacy of GESTECs in the presence of 5-FC based on reductions in density and aggressive tendency of breast cancer cells, as well as pyknosis, karyorrhexis, and karyolysis relative to a negative control. Additionally, expression of PCNA decreased in the stem cells treated group. Treatment of breast cancer cells with 5-fluorouracil (5-FU) increased the expression of pro-apoptotic and anti-proliferative factor, BAX and p21 protein through phosphorylation of p53 and p38. Moreover, analysis of stem cell migratory ability revealed that MDA-MB-231 cells endogenously secreted VEGF, and stem cells expressed their receptor (VEGFR2). To confirm the role of VEGF/VEGFR2 signaling in tumor tropism of stem cells, samples were treated with the VEGFR2 inhibitor, KRN633. The number of migrated stem cells decreased significantly in response to KRN633 due to Erk1/2 activation and PI3K/Akt inhibition. Taken together, these results indicate that treatment with GESTECs, particularly HB1.F3.CD.IFN-β co-expressing CD.IFN-β, may be a useful strategy for treating breast cancer metastasis to the brain in the presence of a prodrug.

  16. Vitamin D supplementation for patients with multiple sclerosis treated with interferon-beta: a randomized controlled trial assessing the effect on flu-like symptoms and immunomodulatory properties

    Science.gov (United States)

    2013-01-01

    Background Flu-like symptoms (FLS) are common side effects of interferon beta (IFN-β) treatment in patients with Multiple Sclerosis (PwMS) and are associated with post-injection cytokine surge. We hypothesized that vitamin D3 supplementation would ameliorate FLS by decreasing related serum cytokines’ levels. Methods In a randomized, double blind study of 45 IFNβ-treated PwMS, 21 patients were assigned to 800 IU of vitamin D3 per day (low dose), while 24 patients received 4,370 IU per day (high dose) for one year. FLS were assessed monthly by telephonic interviews. Serum levels of 25-hydroxy-D (25-OH-D), calcium, PTH, IL-17, IL-10 and IFN-γ were measured periodically. EDSS, relapses, adverse events and quality of life (QoL) were documented. Results 25-OH-D levels increased to a significantly higher levels and PTH levels decreased in the high dose group. There was no significant change in FLS. IL-17 levels were significantly increased in the low dose group, while patients receiving high dose vitamin D had a heterogeneous IL-17 response. No significant differences in relapse rate, EDSS, QoL, serum IL-10 and IFNγ were found. Hypercalcemia or other potential major adverse events were not observed. Conclusion Vitamin D supplementation to IFN−β treated PwMS, at the doses used, seems safe and associated with dose-dependent changes in IL-17 serum levels, while not affecting IFN−β related FLS. Trial registration ClinicalTrials.gov ID: NCT01005095 PMID:23767916

  17. Detection of circulant tumor necrosis factor-alpha , soluble tumor necrosis factor p75 and interferon-gamma in Brazilian patients with dengue fever and dengue hemorrhagic fever

    Directory of Open Access Journals (Sweden)

    Elzinandes LA Braga

    2001-02-01

    Full Text Available Pro-inflammatory cytokines are believed to play an important role in the pathogenesis of dengue infection. This study reports cytokine levels in a total of 54 patients examined in Recife, State of Pernambuco, Brazil. Five out of eight patients who had hemorrhagic manifestations presented tumor necrosis factor-alpha (TNF-alpha levels in sera which were statistically higher than those recorded for controls. In contrast, only one out of 16 patients with mild manifestations had elevated TNF-alpha levels. The levels of interleukin-6 (IL, IL-1beta tested in 24 samples and IL-12 in 30 samples were not significantly increased. Interferon-g was present in 10 out of 30 patients with dengue. The data support the concept that the increased level of TNF-alpha is related to the severity of the disease. Soluble TNF receptor p75 was found in most patients but it is unlikely to be related to severity since it was found with an equivalent frequency and levels in 15 patients with dengue fever and another 15 with dengue hemorrhagic fever.

  18. 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

  19. 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

    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...... 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......-IT was positive in 74% (119/161; 95% CI: 67-81%). Sensitivity was higher in HIV-negative (75/93) than in HIV-positive (44/68) patients (81% vs. 65%, p = 0.02) and increased with CD4 cell count in HIV-positive patients (test for trend p = 0.03). 23 patients (14%) had an indeterminate result and this proportion...

  20. Increased activity of indoleamine 2,3-dioxygenase in serum from acutely infected dengue patients linked to gamma interferon antiviral function

    Science.gov (United States)

    Becerra, Aniuska; Warke, Rajas V.; Xhaja, Kris; Evans, Barbara; Evans, James; Martin, Katherine; de Bosch, Norma; Rothman, Alan L.; Bosch, Irene

    2009-01-01

    The depletion of l-tryptophan (L-Trp) has been associated with the inhibition of growth of micro-organisms and also has profound effects on T cell proliferation and immune tolerance. The enzyme indoleamine 2,3-dioxygenase (IDO) catalyses the rate-limiting step in the catabolic pathway of L-Trp. Gene expression analysis has shown upregulation of genes involved in L-Trp catabolism in in vitro models of dengue virus (DENV) infection. To understand the role of IDO during DENV infection, we measured IDO activity in sera from control and DENV-infected patients. We found increased IDO activity, lower levels of L-Trp and higher levels of l-kynurenine in sera from DENV-infected patients during the febrile days of the disease compared with patients with other febrile illnesses and healthy donors. Furthermore, we confirmed upregulation of IDO mRNA expression in response to DENV infection in vitro, using a dendritic cell (DC) model of DENV infection. We found that the antiviral effect of gamma interferon (IFN-γ) in DENV-infected DCs in vitro was partially dependent on IDO activity. Our results demonstrate that IDO plays an important role in the antiviral effect of IFN-γ against DENV infection in vitro and suggest that it has a role in the immune response to DENV infections in vivo. PMID:19264674

  1. Performance of Interferon-Gamma and IP-10 Release Assays for Diagnosing Latent Tuberculosis Infections in Patients with Concurrent Malaria in Tanzania.

    Science.gov (United States)

    Drabe, Camilla H; Vestergaard, Lasse S; Helleberg, Marie; Nyagonde, Nyagonde; Rose, Michala V; Francis, Filbert; Theilgaard, Ola P; Asbjørn, Jens; Amos, Ben; Bygbjerg, Ib Christian; Ruhwald, Morten; Ravn, Pernille

    2016-04-01

    Interferon-gamma (IFN-γ) release assays (IGRAs) are used to detect cellular immune recognition of Mycobacterium tuberculosis The chemokine IFN-γ-inducible protein 10 (IP-10) is an alternative diagnostic biomarker to IFN-γ. Several conditions interfere with IGRA test performance. We aimed to assess the possible influence of Plasmodium falciparum infection on the IGRA test QuantiFERON-TB GOLD® In-Tube (QFT) test and an in-house IP-10 release assay. In total, 241 Tanzanian adults were included; 184 patients with uncomplicated malaria (88 human immunodeficiency virus [HIV] coinfected) and 57 HIV-infected patients without malaria infection. Malaria was treated with artemether-lumefantrine (Coartem®). QFT testing was performed before initiation of malaria treatment and at days 7 and 42. In total, 172 patients completed follow-up. IFN-γ and IP-10 was measured in QFT supernatants. We found that during malaria infection IFN-γ and IP-10 levels in the unstimulated samples were elevated, mitogen responsiveness was impaired, and CD4 cell counts were decreased. These alterations reverted after malaria treatment. Concurrent malaria infection did not affect QFT test results, whereas there were more indeterminate IP-10 results during acute malaria infection. We suggest that IGRA and IP-10 release assay results of malaria patients should be interpreted with caution and that testing preferably should be postponed until after malaria treatment. PMID:26834199

  2. The Expression of Interleukin-17, Interferon-gamma, and Macrophage Inflammatory Protein-3 Alpha mRNA in Patients with Psoriasis Vulgaris

    Institute of Scientific and Technical Information of China (English)

    李家文; 李东升; 谭志建

    2004-01-01

    Summary: To investigate the role of Interleukin-17 (IL-17), Interferon-gamma (IFN-γ), and macrophage inflammatory protein-3 alpha (MIP-3α) in the pathogenesis of psoriasis, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to semi-quantitatively analyze the mRNA expression of IL 17, IFN-γ, and MIP-3α in 31 psoriatic lesions and 16 normal skin tissues. The results showed that the mRNA of the three cytokines was present in all specimens. And the expression level of IL-17 mRNA in skin lesions was 1. 1416±0. 0591, which was significantly higher than that in normal controls (0. 8788±0. 0344, P<0. 001). The expression levels of IFN-γ mRNA were 1.1142±0. 0561 and 0. 9050±0. 0263, respectively, with significant difference(P<0. 001). And the expression levels of MIP-3α mRNA in psoriatic lesions was 1. 1397 ± 0. 0521, which was markedly higher than that in normal controls (0. 8681±0. 0308, P<0. 001). These findings indicate that up regulated expression of IL-17, IFN-γ, and MIP-3α might be involved in the pathogenesis of psoriasis.

  3. Efficacy and Safety of Immunotherapy with Interferon-Gamma in the Management of Chronic Sulfur Mustard-Induced Cutaneous Complications: Comparison with Topical Betamethasone 1%

    Directory of Open Access Journals (Sweden)

    Yunes Panahi

    2012-01-01

    Full Text Available The present trial investigated the efficacy of immunotherapy with interferon-gamma (IFN-γ in the treatment of sulfur mustard (SM-induced chronic skin complications. Forty subjects who were suffering from chronic skin complications of SM and were diagnosed to have severe atopic dermatitis, were assigned to IFN-γ (50 μg/m2 subcutaneously three times per week (n=20 or betamethasone valerate topical cream 0.1% (n=20 every night for 30 days. Extent and intensity of cutaneous complications was evaluated using scoring atopic dermatitis (SCORAD index, and quality of life using dermatology life quality index (DLQI at baseline and at the end of trial. SCORAD-A and SCORAD-B scores were significantly decreased in both IFN-γ and betamethasone. However, SCORAD-C score was decreased only in the IFN-γ group. There were significant reductions in overall as well as objective SCORAD scores in both groups. As for the magnitude of changes, treatment with IFN-γ was associated with greater reductions in overall, objective and segmented SCORAD scores compared to betamethasone. DLQI reduction was found to be significantly greater in the IFN-γ group. Promising improvements in quality life and clinical symptoms that was observed in the present study suggest the application of IFN-γ as an effective therapy for the management of SM-induced chronic skin complications.

  4. Tryptophan recycling is responsible for the interferon-gamma resistance of Chlamydia psittaci GPIC in indoleamine dioxygenase-expressing host cells.

    Science.gov (United States)

    Wood, Heidi; Roshick, Christine; McClarty, Grant

    2004-05-01

    Comparative genomics indicates that vast differences in Chlamydia sp. host range and disease characteristics can be traced back to subtle variations in gene content within a region of the chromosome termed the plasticity zone. Genes required for tryptophan biosynthesis are located in the plasticity zone; however, the complement of genes encoded varies depending on the chlamydial species examined. Of the sequenced chlamydia genomes, Chlamydia psittaci GPIC contains the most complete tryptophan biosynthesis operon, encoding trpRDCFBA. Immediately downstream of the trp operon are genes encoding kynureninase and ribose phosphate pyrophosphokinase. Here, we show that, in GPIC, these genes are transcribed as a single transcript, the expression of which is regulated by tryptophan. Complementation analyses, using various mutant Escherichia coli isolates, indicate that the tryptophan biosynthesis, kynureninase and ribose phosphate pyrophosphokinase gene products are functional. Furthermore, growth of C. psittaci GPIC in HeLa cells, cultured in tryptophan-free medium, could be rescued by the addition of anthranilate, kynurenine or indole. In total, our results indicate that this complement of genes enables GPIC to recycle tryptophan and thus accounts for the interferon-gamma resistant phenotype displayed in indoleamine-2,3-dioxygenase-expressing host cells. PMID:15101993

  5. 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

  6. 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.

  7. 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.

  8. Tumour necrosis factor alpha, interferon gamma and substance P are novel modulators of extrapituitary prolactin expression in human skin.

    Science.gov (United States)

    Langan, Ewan A; Vidali, Silvia; Pigat, Natascha; Funk, Wolfgang; Lisztes, Erika; Bíró, Tamás; Goffin, Vincent; Griffiths, Christopher E M; Paus, Ralf

    2013-01-01

    Human scalp skin and hair follicles (HFs) are extra-pituitary sources of prolactin (PRL). However, the intracutaneous regulation of PRL remains poorly understood. Therefore we investigated whether well-recognized regulators of pituitary PRL expression, which also impact on human skin physiology and pathology, regulate expression of PRL and its receptor (PRLR) in situ. This was studied in serum-free organ cultures of microdissected human scalp HFs and skin, i.e. excluding pituitary, neural and vascular inputs. Prolactin expression was confirmed at the gene and protein level in human truncal skin, where its expression significantly increased (p = 0.049) during organ culture. There was, however, no evidence of PRL secretion into the culture medium as measured by ELISA. PRL immunoreactivity (IR) in female human epidermis was decreased by substance P (p = 0.009), while neither the classical pituitary PRL inhibitor, dopamine, nor corticotropin-releasing hormone significantly modulated PRL IR in HFs or skin respectively. Interferon (IFN) γ increased PRL IR in the epithelium of human HFs (p = 0.044) while tumour necrosis factor (TNF) α decreased both PRL and PRLR IR. This study identifies substance P, TNFα and IFNγ as novel modulators of PRL and PRLR expression in human skin, and suggests that intracutaneous PRL expression is not under dopaminergic control. Given the importance of PRL in human hair growth regulation and its possible role in the pathogenesis of several common skin diseases, targeting intracutaneous PRL production via these newly identified regulatory pathways may point towards novel therapeutic options for inflammatory dermatoses. PMID:23626671

  9. Tumour necrosis factor alpha, interferon gamma and substance P are novel modulators of extrapituitary prolactin expression in human skin.

    Science.gov (United States)

    Langan, Ewan A; Vidali, Silvia; Pigat, Natascha; Funk, Wolfgang; Lisztes, Erika; Bíró, Tamás; Goffin, Vincent; Griffiths, Christopher E M; Paus, Ralf

    2013-01-01

    Human scalp skin and hair follicles (HFs) are extra-pituitary sources of prolactin (PRL). However, the intracutaneous regulation of PRL remains poorly understood. Therefore we investigated whether well-recognized regulators of pituitary PRL expression, which also impact on human skin physiology and pathology, regulate expression of PRL and its receptor (PRLR) in situ. This was studied in serum-free organ cultures of microdissected human scalp HFs and skin, i.e. excluding pituitary, neural and vascular inputs. Prolactin expression was confirmed at the gene and protein level in human truncal skin, where its expression significantly increased (p = 0.049) during organ culture. There was, however, no evidence of PRL secretion into the culture medium as measured by ELISA. PRL immunoreactivity (IR) in female human epidermis was decreased by substance P (p = 0.009), while neither the classical pituitary PRL inhibitor, dopamine, nor corticotropin-releasing hormone significantly modulated PRL IR in HFs or skin respectively. Interferon (IFN) γ increased PRL IR in the epithelium of human HFs (p = 0.044) while tumour necrosis factor (TNF) α decreased both PRL and PRLR IR. This study identifies substance P, TNFα and IFNγ as novel modulators of PRL and PRLR expression in human skin, and suggests that intracutaneous PRL expression is not under dopaminergic control. Given the importance of PRL in human hair growth regulation and its possible role in the pathogenesis of several common skin diseases, targeting intracutaneous PRL production via these newly identified regulatory pathways may point towards novel therapeutic options for inflammatory dermatoses.

  10. 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)

  11. Pesquisa de interferon gama em tecido periodontal de ratos submetidos à movimentação dentária induzida Gamma-interferon investigation in rat periodontal tissue under induced dental movement

    Directory of Open Access Journals (Sweden)

    Daniel Mascarenhas da Silveira

    2009-04-01

    such as sub products of arachidonic acid and cytokines are released. To interferon-gamma (INF-γ , a main cytokine released after induction of adaptive immune response, is attributed the function of attracting the macrophages, which aids in removing cell rests and promote healing and reorganization of the inflamed areas. AIM: Given that some biological aspects that permeate dental movement are not yet fully clear, we aimed in this study to investigate INF-γ expression in the periodontium of rats under orthodontic movement. METHODS: The sample was composed of 9 rats, whose first upper right molars were moved with a force of 0,5N, for 3, 7 and 14 days. The left molars were used as controls. RESULTS: Through immunohistochemistry, we verified the absence of INF-γ expression in almost all the studied tissues, in both the traction and pressure sides.

  12. 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

  13. Determination of differential dose rates in a mixed beta and gamma field using shielded Al2O3:C : Results of Monte Carlo modelling

    DEFF Research Database (Denmark)

    Aznar, M.C.; Nathan, R.; Murray, A.S.;

    2003-01-01

    Mixed beta and gamma heterogeneous radiation fields are found in many circumstances, ranging from retrospective dosimetry to medical therapy treatments. It can be very important to provide a direct measurement of the contribution to dose rate from beta particles and gamma rays separately...... outline the results of our modelling of the most appropriate encapsulation for Al2O3: C luminescence dosimeters when used to measure the dose rate from natural radiation fields. We consider a configuration where one Al2O3: C chip of a pair is enclosed in a beta-thin light-tight package (which would allow...

  14. 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

  15. Selective binding of chiral molecules of cinchona alkaloid by beta- and gamma-cyclodextrins and organoselenium-bridged bis(beta-cyclodextrin)s.

    Science.gov (United States)

    Liu, Yu; Li, Li; Zhang, Heng-Yi; Fan, Zhi; Guan, Xu-Dong

    2003-02-01

    The inclusion complexation behavior of chiral members of cinchona alkaloid with beta- and gamma-cyclodextrins (1 and 2) and 6,6(')-trimethylenediseleno-bridged bis(beta-cyclodextrin) (3) was assessed by means of fluorescence and 2D-NMR spectroscopy. The spectrofluorometric titrations have been performed in aqueous buffer solution (pH 7.20) at 25.0 degrees C to determine the stability constants of the inclusion complexation of 1-3 with guest molecules (i.e., cinchonine, cinchonidine, quinine, and quinidine) in order to quantitatively investigate the molecular selective binding ability. The stability constants of the resulting complexes of 2 with guest molecules are larger than that of 1. As a result of cooperative binding, the stability constants of inclusion complexation of dimeric beta-cyclodextrin 3 with cinchonidine and cinchonine are higher than that of parent 1 by factor of 4.5 and 2.4, respectively. These results are discussed from the viewpoint of the size-fit and geometric complementary relationship between the host and guest.

  16. An approach to the determination of the ability of human cells to repair gamma-radiation-induced DNA damages with the help of interferon

    International Nuclear Information System (INIS)

    The method of ultracentrifugation of a nucleoid in a neutral sucrose gradient in the presence of ethidium bromide was used to detect γ-radiation-induced DNA breaks and their resynthesis in human HEp-2 cells and fibroblasts taken from a skin biopsy of patients with homocystinuria (HCN). In HEp-2 cells pretreated with interferon the nucleoid sedimentation rate after γ-irradiation did not differ fom that in intact cells, that is, interferon exerted its protective effect whereas in HCN cells interferon was ineffective. After incubation with interferon, the resynthesis of the induced breaks was enhanced in these cells as well

  17. Pile-up corrections for high-precision superallowed {beta} decay half-life measurements via {gamma}-ray photopeak counting

    Energy Technology Data Exchange (ETDEWEB)

    Grinyer, G.F. [Department of Physics, University of Guelph, Guelph, Ont, N1G 2W1 (Canada)], E-mail: ggrinyer@physics.uoguelph.ca; Svensson, C.E.; Andreoiu, C. [Department of Physics, University of Guelph, Guelph, Ont, N1G 2W1 (Canada); Andreyev, A.N. [TRIUMF, 4004 Wesbrook Mall, Vancouver, BC, V6T 2A3 (Canada); Austin, R.A.E. [Department of Astronomy and Physics, St. Mary' s University, Halifax, NS, B3H 3C3 (Canada); Ball, G.C. [TRIUMF, 4004 Wesbrook Mall, Vancouver, BC, V6T 2A3 (Canada); Bandyopadhyay, D. [Department of Physics, University of Guelph, Guelph, Ont, N1G 2W1 (Canada); Chakrawarthy, R.S. [TRIUMF, 4004 Wesbrook Mall, Vancouver, BC, V6T 2A3 (Canada); Finlay, P. [Department of Physics, University of Guelph, Guelph, Ont, N1G 2W1 (Canada); Garrett, P.E. [Department of Physics, University of Guelph, Guelph, Ont, Canada N1G 2W1 (Canada); TRIUMF, 4004 Wesbrook Mall, Vancouver, BC, V6T 2A3 (Canada); Hackman, G. [TRIUMF, 4004 Wesbrook Mall, Vancouver, BC, V6T 2A3 (Canada); Hyland, B. [Department of Physics, University of Guelph, Guelph, Ont, N1G 2W1 (Canada); Kulp, W.D. [School of Physics, Georgia Institute of Technology, Atlanta, GA 30332 0430 (United States); Leach, K.G. [Department of Physics, University of Guelph, Guelph, Ont, N1G 2W1 (Canada); Leslie, J.R. [Department of Physics, Queen' s University, Kingston, Ont., K7L 3N6 (Canada); Morton, A.C.; Pearson, C.J. [TRIUMF, 4004 Wesbrook Mall, Vancouver, BC, V6T 2A3 (Canada); Phillips, A.A. [Department of Physics, University of Guelph, Guelph, Ont, N1G 2W1 (Canada); Sarazin, F. [Department of Physics, Colorado School of Mines, Golden, CO 80401 (United States); Schumaker, M.A. [Department of Physics, University of Guelph, Guelph, Ont, N1G 2W1 (Canada)] (and others)

    2007-09-11

    A general technique that corrects {gamma}-ray gated {beta} decay-curve data for detector pulse pile-up is presented. The method includes corrections for non-zero time-resolution and energy-threshold effects in addition to a special treatment of saturating events due to cosmic rays. This technique is verified through a Monte Carlo simulation and experimental data using radioactive beams of {sup 26}Na implanted at the center of the 8{pi}{gamma}-ray spectrometer at the ISAC facility at TRIUMF in Vancouver, Canada. The {beta}-decay half-life of {sup 26}Na obtained from counting 1809-keV {gamma}-ray photopeaks emitted by the daughter {sup 26}Mg was determined to be T{sub 1/2}=1.07167{+-}0.00055s following a 27{sigma} correction for detector pulse pile-up. This result is in excellent agreement with the result of a previous measurement that employed direct {beta} counting and demonstrates the feasibility of high-precision {beta}-decay half-life measurements through the use of high-purity germanium {gamma}-ray detectors. The technique presented here, while motivated by superallowed-Fermi {beta} decay studies, is general and can be used for all half-life determinations (e.g. {alpha}-, {beta}-, X-ray, fission) in which a {gamma}-ray photopeak is used to select the decays of a particular isotope.

  18. Structure of the T-cell receptor in a Ti alpha beta, Ti gamma delta double positive T-cell line

    DEFF Research Database (Denmark)

    Kuhlmann, J; Geisler, C

    1993-01-01

    is still not known. It has been suggested that each T-cell receptor contains two Ti dimers. To gain insight into the structure of the T-cell receptor we constructed a Ti alpha beta, Ti gamma delta double positive T-cell line which contained four functional Ti chains (Ti alpha, beta, gamma, and delta......The multichain T-cell receptor is composed of at least six different polypeptide chains. The clonotypic Ti heterodimer (Ti alpha beta or Ti gamma delta) is non-covalently associated with the CD3 chains (CD3 gamma delta epsilon zeta). The exact number of subunits constituting the T-cell receptor......). The data demonstrated an absence of Ti dimers containing mixtures of chains other than the typical Ti alpha beta and Ti gamma delta combinations. Furthermore, by co-modulation experiments we demonstrated that the Ti alpha beta and the Ti gamma delta dimers were not expressed in the same T-cell receptor...

  19. Interferon gamma-dependent intestinal pathology contributes to the lethality in bacterial superantigen-induced toxic shock syndrome.

    Directory of Open Access Journals (Sweden)

    Ashenafi Y Tilahun

    Full Text Available Toxic shock syndrome (TSS caused by the superantigen exotoxins of Staphylococcus aureus and Streptococcus pyogenes is characterized by robust T cell activation, profound elevation in systemic levels of multiple cytokines, including interferon-γ (IFN-γ, followed by multiple organ dysfunction and often death. As IFN-γ possesses pro- as well as anti-inflammatory properties, we delineated its role in the pathogenesis of TSS. Antibody-mediated in vivo neutralization of IFN-γ or targeted disruption of IFN-γ gene conferred significant protection from lethal TSS in HLA-DR3 transgenic mice. Following systemic high dose SEB challenge, whereas the HLA-DR3.IFN-γ(+/+ mice became sick and succumbed to TSS, HLA-DR3.IFN-γ(-/- mice appeared healthy and were significantly protected from SEB-induced lethality. SEB-induced systemic cytokine storm was significantly blunted in HLA-DR3.IFN-γ(-/- transgenic mice. Serum concentrations of several cytokines (IL-4, IL-10, IL-12p40 and IL-17 and chemokines (KC, rantes, eotaxin and MCP-1 were significantly lower in HLA-DR3.IFN-γ(-/- transgenic mice. However, SEB-induced T cell expansion in the spleens was unaffected and expansion of SEB-reactive TCR Vβ8(+ CD4(+ and CD8(+ T cells was even more pronounced in HLA-DR3.IFN-γ(-/- transgenic mice when compared to HLA-DR3.IFN-γ(+/+ mice. A systematic histopathological examination of several vital organs revealed that both HLA-DR3.IFN-γ(+/+ and HLA-DR3.IFN-γ(-/- transgenic mice displayed comparable severe inflammatory changes in lungs, and liver during TSS. Remarkably, whereas the small intestines from HLA-DR3.IFN-γ(+/+ transgenic mice displayed significant pathological changes during TSS, the architecture of small intestines in HLA-DR3.IFN-γ(-/- transgenic mice was preserved. In concordance with these histopathological changes, the gut permeability to macromolecules was dramatically increased in HLA-DR3.IFN-γ(+/+ but not HLA-DR3.IFN-γ(-/- mice during TSS. Overall

  20. Predictors of persistently positive Mycobacterium-tuberculosis-specific interferon-gamma responses in the serial testing of health care workers

    Directory of Open Access Journals (Sweden)

    Schultze-Werninghaus Gerhard

    2010-07-01

    Full Text Available Abstract Background Data on the performance of Mycobacterium-tuberculosis-specific interferon-(IFN-γ release assays (IGRAs in the serial testing of health care workers (HCWs is limited. The objective of the present study was to determine the frequency of IGRA conversions and reversions and to identify predictors of persistent IGRA positivity among serially tested German HCWs in the absence of recent extensive tuberculosis (TB exposure. Methods In this observational cohort-study HCWs were prospectively recruited within occupational safety and health measures and underwent a tuberculin skin test (TST and the IGRA QuantiFERON®-TB Gold In-Tube (QFT-GIT at baseline. The QFT-GIT was repeated 18 weeks later in the median. QFT-GIT conversions (and reversions were defined as baseline IFN-γ Results In total, 18 (9.9% and 15 (8.2% of 182 analyzed HCWs were QFT-GIT-positive at baseline and at follow-up, respectively. We observed a strong overall agreement between baseline and follow-up QFT-GIT results (κ = 0.70. Reversions (6/18, 33.3% occurred more frequently than conversions (3/162, 1.9%. Age and positive prior and recent TST results independently predicted persistent QFT-GIT positivity. Furthermore, the chance of having persistently positive QFT-GIT results raised about 3% with each additional 0.1 IU/ml increase in the baseline IFN-γ response (adjusted odds ratio 1.03, 95% confidence interval 1.01-1.04. No active TB cases were detected within an observational period of more than two years. Conclusions The QFT-GIT's utility for the application in serial testing was limited by a substantial proportion of reversions. This shortcoming could be overcome by the implementation of a borderline zone for the interpretation of QFT-GIT results. However, further studies are needed to clearly define the within-subject variability of the QFT-GIT and to confirm that increasing age, concordantly positive TST results, and the extend of baseline IFN-γ responses may

  1. 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; Frederiksen, Jette Lautrup; Søgaard, Lise Vejby;

    2009-01-01

    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....... INTERPRETATION: Oral methylprednisolone given in pulses every 4 weeks as an add-on therapy to subcutaneous interferon beta-1a in patients with relapsing-remitting multiple sclerosis leads to a significant reduction in relapse rate. However, because of the small number of patients and the high dropout rate...

  2. 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)

  3. Pure phase-locking of beta/gamma oscillation contributes to the N30 frontal component of somatosensory evoked potentials

    Directory of Open Access Journals (Sweden)

    Leroy Axelle

    2007-09-01

    Full Text Available Abstract Background Evoked potentials have been proposed to result from phase-locking of electroencephalographic (EEG activities within specific frequency bands. However, the respective contribution of phasic activity and phase resetting of ongoing EEG oscillation remains largely debated. We here applied the EEGlab procedure in order to quantify the contribution of electroencephalographic oscillation in the generation of the frontal N30 component of the somatosensory evoked potentials (SEP triggered by median nerve electrical stimulation at the wrist. Power spectrum and intertrial coherence analysis were performed on EEG recordings in relation to median nerve stimulation. Results The frontal N30 component was accompanied by a significant phase-locking of beta/gamma oscillation (25–35 Hz and to a lesser extent of 80 Hz oscillation. After the selection in each subject of the trials for which the power spectrum amplitude remained unchanged, we found pure phase-locking of beta/gamma oscillation (25–35 Hz peaking about 30 ms after the stimulation. Transition across trials from uniform to normal phase distribution revealed temporal phase reorganization of ongoing 30 Hz EEG oscillations in relation to stimulation. In a proportion of trials, this phase-locking was accompanied by a spectral power increase peaking in the 30 Hz frequency band. This corresponds to the complex situation of 'phase-locking with enhancement' in which the distinction between the contribution of phasic neural event versus EEG phase resetting is hazardous. Conclusion The identification of a pure phase-locking in a large proportion of the SEP trials reinforces the contribution of the oscillatory model for the physiological correlates of the frontal N30. This may imply that ongoing EEG rhythms, such as beta/gamma oscillation, are involved in somatosensory information processing.

  4. Lower expression of mRNA for interferon-gamma in T helper cells of children with newly diagnosed lymphomas

    Directory of Open Access Journals (Sweden)

    Michał Matysiak

    2011-08-01

    Full Text Available The complex interactions between cancer and host cells are far from being fully elucidated. Assessment of Th1/Th2/Th3/Tr1 balance is an interesting approach to explain immunological disturbances in lymphomas. The aim of our study was to assess mRNA for pro- and anti-inflammatory cytokines in T-cells in 20 children with Hodgkin- and non-Hodgkin lymphomas. CD4+ and CD8+ cells were isolated from whole peripheral blood and four different cytokine mRNA levels (IFN-γ, IL-10, IL-4, TGF-β were determined by real-time PCR technique. Comparing to the control group, we found lower expression of mRNA for IFN-gamma in CD4+ cells at the time of lymphoma diagnosis. It may be one of the pathogenetic mechanisms of impaired immunity in these patients.

  5. Bi-phasic effect of interferon (IFN)-alpha: IFN-alpha up- and down-regulates interleukin-4 signaling in human T cells

    DEFF Research Database (Denmark)

    Eriksen, Karsten Wessel; Sommer, Viveca Horst; Woetmann, Anders;

    2003-01-01

    Interferon (IFN)-alpha/beta is produced by virally infected cells and is believed to play an important role in early phases of the innate immune response. In addition, IFN-alpha/beta inhibits interleukin (IL)-4 signaling in B cells and monocytes, suggesting that IFN-alpha/beta (like IFN-gamma) is......Interferon (IFN)-alpha/beta is produced by virally infected cells and is believed to play an important role in early phases of the innate immune response. In addition, IFN-alpha/beta inhibits interleukin (IL)-4 signaling in B cells and monocytes, suggesting that IFN-alpha/beta (like IFN......-4-mediated STAT6 activation in both CD4+ and CD8+ human T cells. The effect is specific because (i) another interferon, IFN-gamma, does not enhance IL-4-mediated STAT6 activation, (ii) IFN-alpha-mediated STAT1 and STAT2 activation is not modulated by IL-4, and (iii) activation of Janus kinases...

  6. Lightweight High Temperature Beta Gamma Alloy/Process Development for Disk and Blade Applications Project

    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,...

  7. Sensorimotor and cognitive involvement of the beta-gamma oscillation in the frontal N30 component of somatosensory evoked potentials.

    Science.gov (United States)

    Cebolla, A M; Cheron, G

    2015-12-01

    The most consistent negative cortical component of somatosensory evoked potentials (SEPs), namely the frontal N30, can be considered more multidimensional than a strict item of standard somatosensory investigation, dedicated to tracking the afferent volley from the peripheral sensory nerve potentials to the primary somatosensory cortex. In this review, we revisited its classical sensorimotor implication within the framework of the recent oscillatory model of ongoing electroencephalogram (EEG) rhythms. Recently, the N30 component was demonstrated to be related to an increase in the power of beta-gamma EEG oscillation and a phase reorganization of the ongoing EEG oscillations (phase locking) in this frequency band. Thanks to high density EEG recordings and the inverse modeling method (swLORETA), it was shown that different overlapping areas of the motor and premotor cortex are specifically involved in generating the N30 in the form of a beta gamma oscillatory phase locking and power increase. This oscillatory approach has allowed a re-investigation of the movement gating behavior of the N30. It was demonstrated that the concomitant execution of finger movements by a stimulated hand impinges the temporal concentration of the ongoing beta/gamma EEG oscillations and abolished the N30 component. It was hypothesized that the involvement of neuronal populations in both the sensorimotor cortex and other related areas were unable to respond to the phasic sensory activation so could not phase-lock their oscillatory signals to the external sensory input during the movement. In this case, the actual movement has primacy over the artificial somatosensory input. The contribution of the ongoing oscillatory activity in the N30 emergence calls for a reappraisal of fundamental and clinical interpretations of the frontal N30 component. An absent or reduced amplitude of the N30 can now be viewed not only as a deficit in the activation of the somatosensory synaptic network in response

  8. 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.)

  9. 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

    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...... of these antigens in vivo was found in 11 of 12 examined patients with primary bronchial carcinoma. A concomitant increase in serum beta 2m (median 90%, P less than 0.001) was found in all patients. In contrast the amount of cell-associated HLA-ABC and beta 2m remained unchanged (P greater than 0.1 and P greater...

  10. 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.

  11. Interferon-gamma release assays for the diagnosis of active tuberculosis in HIV-infected patients: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Jun Chen

    Full Text Available BACKGROUND: Interferon-gamma release assays (IGRAs have provided a new method for the diagnosis of Mycobacterium tuberculosis infection. However, the role of IGRAs for the diagnosis of active tuberculosis (TB, especially in HIV-infected patients remains unclear. METHODS: We searched PubMed, EMBASE and Cochrane databases to identify studies published in January 2001-July 2011 that evaluated the evidence of using QuantiFERON-TB Gold in-tube (QFT-GIT and T-SPOT.TB (T-SPOT on blood for the diagnosis of active TB in HIV-infected patients. RESULTS: The search identified 16 eligible studies that included 2801 HIV-infected individuals (637 culture confirmed TB cases. The pooled sensitivity for the diagnosis of active TB was 76.7% (95%CI, 71.6-80.5% and 77.4% (95%CI, 71.4-82.6% for QFT-GIT and T-SPOT, respectively, while the specificity was 76.1% (95%CI, 74.0-78.0% and 63.1% (95%CI, 57.6-68.3% after excluding the indeterminate results. Studies conducted in low/middle income countries showed slightly lower sensitivity and specificity when compared to that in high-income countries. The proportion of indeterminate results was as high as 10% (95%CI, 8.8-11.3% and 13.2% (95%CI, 10.6-16.0% for QFT-GIT and T-SPOT, respectively. CONCLUSION: IGRAs in their current formulations have limited accuracy in diagnosing active TB in HIV-infected patients, and should not be used alone to rule out or rule in active TB cases in HIV-infected patients. Further modification is needed to improve their accuracy.

  12. Interferon Gamma Release Assay versus Tuberculin Skin Testing among Healthcare Workers of Highly Diverse Origin in a Moderate Tuberculosis Burden Country.

    Science.gov (United States)

    Al Hajoj, Sahal; Varghese, Bright; Datijan, Alria; Shoukri, Mohammed; Alzahrani, Ali; Alkhenizan, Abdallah; AlSaif, Abdulaziz; Althawadi, Sahar; Fernandez, Grace; Alrajhi, Abdulrahman

    2016-01-01

    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 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 factors associated with the discordance were origin of the candidate (p value Origin of the candidates has strong association with the results of TST and QFT. The discordant results particularly TST negative and QFT positive needs more detailed analysis. PMID:27148876

  13. The Clinical Usefulness of Tuberculin Skin Test versus Interferon-Gamma Release Assays for Diagnosis of Latent Tuberculosis in HIV Patients: A Meta-Analysis

    Science.gov (United States)

    Ayubi, Erfan; Doosti-Irani, Amin; Sanjari Moghaddam, Ali; Sani, Mohadeseh; Nazarzadeh, Milad; Mostafavi, Ehsan

    2016-01-01

    Background Accurate diagnosis of latent tuberculosis infection (LTBI) is becoming increasingly concerning due to the increasing the HIV epidemic, which have increased the risk for reactivation to active tuberculosis (TB) infection. LTBI is diagnosed by tuberculin skin test (TST) and interferon-gamma release assays (IGRAs). Objectives The aim of the present study was to conduct a meta-analysis of published papers on the agreement (kappa) between TST and QuantiFERON-TB Gold In-Tube (QFT-GIT) tests for diagnosis of LTBI in HIV patient. Methods Electronic databases including PubMed/Medline, Elsevier/Scopus and Embase/Ovid were reviewed up Jan. 2016. We performed a random effect model meta-analysis for estimation of pooled Kappa between the two methods of diagnosis. Meta regression was used for assessing potential heterogeneity and Egger’s test was used for assessing small study effect and publication bias. Results The initial search strategy produced 6744 records. Of them, 23 cross-sectional studies met the inclusion criteria and 20 studies entered in meta-analysis. The pooled kappa was and prevalence-adjusted and bias-adjusted kappa (PABAK) were 0.37 (95% CI: 0.28, 0.46) and 0.59 (0.49, 0.69). The discordance of TST-/QFT-GIT+ was more than TST+/QFT-GIT-. Kappa estimate between two tests was linearly associated with age and prevalence index and inversely associated with bias index. Conclusion Fair agreement between TST and QFT-GIT makes it difficult to know whether TST is as useful as the QFT-GIT in HIV-infected patients. The higher discordance of TST-/QFT-GIT+ in compared to TST+/QFT-GIT- can induce the higher sensitivity of QFT-GIT for diagnosis LTBI in HIV patients. Disagreement between two tests can be influenced by error in measurements and prevalence of HIV. PMID:27622293

  14. 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)

    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

  15. Infection-stimulated Anemia Results Primarily from Interferon Gamma-dependent, Signal Transducer and Activator of Transcription 1-independent Red Cell Loss

    Institute of Scientific and Technical Information of China (English)

    Zheng Wang; Dong-Xia Zhang; Qi Zhao

    2015-01-01

    Background:Although the onset of anemia during infectious disease is commonly correlated with production of inflammatory cytokines,the mechanisms by which cytokines induce anemia are poorly defined.This study focused on the mechanism research.Methods:Different types of mice were infected perorally with Toxoplasma gondii strain ME49.At the indicated times,samples from each mouse were harvested,processed,and analyzed individually.Blood samples were analyzed using a Coulter Counter and red blood cell (RBC) survival was measured by biotinylation.Levels of tumor necrosis factor-α (TNF-α),inducible nitric oxide synthase (iNOS),and inducible protein 10 (IP-10) mRNA in liver tissue were measured by real-time polymerase chain reaction.Results:T.gondii-infected mice exhibited anemia due to a decrease in both erythropoiesis and survival time of RBC in the circulation (P < 0.02).In addition,infection-stimulated anemia was associated with fecal occult,supporting previous literature that hemorrhage is a consequence of T.gondii infection in mice.Infection-induced anemia was abolished in interferon gamma (IFNγ) and IFNγ receptor deficient mice (P < 0.05) but was still evident in mice lacking TNF-α,iNOS,phagocyte NADPH oxidase or IP-10 (P < 0.02).Neither signal transducer and activator of transcription 1 (STAT1) deficient mice nor 129S6 controls exhibited decreased erythropoiesis,but rather suffered from an anemia resulting solely from increased loss of circulating RBC.Conclusions:Infection-stimulated decrease in erythropoiesis and losses of RBC have distinct mechanistic bases.These results show that during T.gondii infection,IFNγ is responsible for an anemia that results from both a decrease in erythropoiesis and a STAT1 independent loss of circulating RBC.

  16. Interferon Gamma Release Assay versus Tuberculin Skin Testing among Healthcare Workers of Highly Diverse Origin in a Moderate Tuberculosis Burden Country.

    Science.gov (United States)

    Al Hajoj, Sahal; Varghese, Bright; Datijan, Alria; Shoukri, Mohammed; Alzahrani, Ali; Alkhenizan, Abdallah; AlSaif, Abdulaziz; Althawadi, Sahar; Fernandez, Grace; Alrajhi, Abdulrahman

    2016-01-01

    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 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 factors associated with the discordance were origin of the candidate (p value Origin of the candidates has strong association with the results of TST and QFT. The discordant results particularly TST negative and QFT positive needs more detailed analysis.

  17. 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.

  18. Multidrug-resistant tuberculosis outbreak in an Italian prison: tolerance of pyrazinamide plus levofloxacin prophylaxis and serial interferon gamma release assays.

    Science.gov (United States)

    Bedini, A; Garlassi, E; Stentarelli, C; Petrella, S; Meacci, M; Meccugni, B; Meschiari, M; Franceschini, E; Cerri, S; Brasacchio, A; Rumpianesi, F; Richeldi, L; Mussini, C

    2016-07-01

    The optimal treatment for latent tuberculosis infection (LTBI) in subjects exposed to multidrug-resistant (MDR) tuberculosis (TB) remains unclear, and the change in response of the QuantiFERON-TB Gold In-Tube (QTB-IT) test during and after treatment is unknown. Between May 2010 and August 2010, 39 prisoners at the 'Casa Circondariale' of Modena, Italy, were exposed to a patient with active pulmonary MDR TB. All contacts were tested with the tuberculin skin test and QTB-IT. Upon exclusion of active TB, subjects positive to both tests were offered 6 months' treatment with pyrazinamide (PZA) and levofloxacin (LVX). QTB-IT testing was repeated at 3 and 6 months after initial testing in all subjects who were offered LTBI treatment. Seventeen (43.5%) of 39 subjects tested positive to both tuberculin skin test and QTB-IT test, and 12 (70.5%) agreed to receive therapy with PZA and LVX at standard doses. Only five (41.6%) of 12 subjects completed 6 months' treatment. Reasons for discontinuation were asymptomatic hepatitis, gastritis and diarrhoea. The QTB-IT values decreased in all subjects who completed the treatment, in two (33%) of six of those who received treatment for less than 3 months and in one (50%) of two patients who discontinued therapy after 3 months. The QTB-IT test results never turned negative. Despite the small number of subjects, the study confirmed that PZA plus LVX is a poorly tolerated option for MDR LTBI treatment. We observed a large degree of variation in the results of the QTB-IT test results among participants. The study confirmed that the interferon gamma release assay is not a reliable tool for monitoring the treatment of MDR LTBI in clinical practice. PMID:27222718

  19. Analysis of the interferon gamma (rs2430561, +874T/A functional gene variant in relation to the presence of cardiovascular events in rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Mercedes García-Bermúdez

    Full Text Available OBJECTIVE: Rheumatoid arthritis (RA is a chronic inflammatory disease associated with increased cardiovascular (CV morbidity and mortality. Since interferon-gamma (IFN-γ has a direct effect on inflammation, in this study we assessed the potential association of the IFNG functional gene variant rs2430561 with CV disease in patients with RA. METHODS: One thousand six hundred and thirty-five patients fulfilling the 1987 American College of Rheumatology classification criteria for RA were genotyped for the IFNG (rs2430561, +874T/A gene polymorphism using TaqMan genotyping assay. Patients were stratified according to the presence of CV events or not. Logistic regression models to explain the presence of CV disease according to the IFNG rs2430561 allele distribution were performed. The potential influence of this variant in the development of subclinical atherosclerosis was also analyzed in a subgroup of patients with no history of CV events to determine carotid artery intima-media thickness (IMT (n = 286 and presence of carotid plaques. Levels of the cytokine were determined in a subgroup of patients by ELISA. RESULTS: Adjusted logistic regression model disclosed that presence of the minor allele A was not associated with increased risk of suffering CV events in RA patients. Besides, differences did not achieve statistical significance regarding carotid IMT and presence of carotid plaques in RA patients carrying IFNG rs2430561 variant allele. Levels of IFN-γ were higher in patients who had suffered CV events compared to patients who did not. CONCLUSION: Our results do not support a role of IFNG rs2430561 (+874T/A functional gene variant in the development of CV disease in RA patients.

  20. How methodologic differences affect results of economic analyses: a systematic review of interferon gamma release assays for the diagnosis of LTBI.

    Directory of Open Access Journals (Sweden)

    Olivia Oxlade

    Full Text Available INTRODUCTION: Cost effectiveness analyses (CEA can provide useful information on how to invest limited funds, however they are less useful if different analysis of the same intervention provide unclear or contradictory results. The objective of our study was to conduct a systematic review of methodologic aspects of CEA that evaluate Interferon Gamma Release Assays (IGRA for the detection of Latent Tuberculosis Infection (LTBI, in order to understand how differences affect study results. METHODS: A systematic review of studies was conducted with particular focus on study quality and the variability in inputs used in models used to assess cost-effectiveness. A common decision analysis model of the IGRA versus Tuberculin Skin Test (TST screening strategy was developed and used to quantify the impact on predicted results of observed differences of model inputs taken from the studies identified. RESULTS: Thirteen studies were ultimately included in the review. Several specific methodologic issues were identified across studies, including how study inputs were selected, inconsistencies in the costing approach, the utility of the QALY (Quality Adjusted Life Year as the effectiveness outcome, and how authors choose to present and interpret study results. When the IGRA versus TST test strategies were compared using our common decision analysis model predicted effectiveness largely overlapped. IMPLICATIONS: Many methodologic issues that contribute to inconsistent results and reduced study quality were identified in studies that assessed the cost-effectiveness of the IGRA test. More specific and relevant guidelines are needed in order to help authors standardize modelling approaches, inputs, assumptions and how results are presented and interpreted.

  1. Defect of CARD9 leads to impaired accumulation of gamma interferon-producing memory phenotype T cells in lungs and increased susceptibility to pulmonary infection with Cryptococcus neoformans.

    Science.gov (United States)

    Yamamoto, Hideki; Nakamura, Yuri; Sato, Ko; Takahashi, Yurie; Nomura, Toshiki; Miyasaka, Tomomitsu; Ishii, Keiko; Hara, Hiromitsu; Yamamoto, Natsuo; Kanno, Emi; Iwakura, Yoichiro; Kawakami, Kazuyoshi

    2014-04-01

    Caspase recruitment domain-containing protein 9 (CARD9) is an adaptor molecule signal that is critical for NF-κB activation and is triggered through C-type lectin receptors (CLRs), which are pattern recognition receptors that recognize carbohydrate structures. Previous studies have reported that Cryptococcus neoformans, a fungal pathogen that causes meningoencephalitis in AIDS patients, is recognized through some CLRs, such as mannose receptors or DC-SIGN. However, the role of CARD9 in the host defense against cryptococcal infection remains to be elucidated. In the present study, we analyzed the role of CARD9 in the host defense against pulmonary infection with C. neoformans. CARD9 gene-disrupted (knockout [KO]) mice were highly susceptible to this infection, as shown by the reduced fungal clearance in the infected lungs of CARD9 KO mice, compared to that in wild-type (WT) mice. Gamma interferon (IFN-γ) production was strongly reduced in CARD9 KO mice during the innate-immunity phase of infection. Reduced IFN-γ synthesis was due to impaired accumulation of NK and memory phenotype T cells, which are major sources of IFN-γ innate-immunity-phase production; a reduction in the accumulation of these cells was correlated with reduced CCL4, CCL5, CXCL9, and CXCL10 synthesis. However, differentiation of Th17 cells, but not of Th1 cells, was impaired at the adaptive-immunity phase in CARD9 KO mice compared to WT mice, although there was no significant difference in the infection susceptibility between interleukin 17A (IL-17A) KO and WT mice. These results suggest that CARD9 KO mice are susceptible to C. neoformans infection probably due to the reduced accumulation of IFN-γ-expressing NK and memory phenotype T cells at the early stage of infection. PMID:24470469

  2. Card9- and MyD88-Mediated Gamma Interferon and Nitric Oxide Production Is Essential for Resistance to Subcutaneous Coccidioides posadasii Infection.

    Science.gov (United States)

    Hung, Chiung-Yu; Castro-Lopez, Natalia; Cole, Garry T

    2016-04-01

    Coccidioidomycosis is a potentially life-threatening respiratory disease which is endemic to the southwestern United States and arid regions of Central and South America. It is responsible for approximately 150,000 infections annually in the United States alone. Almost every human organ has been reported to harbor parasitic cells of Coccidioides spp. in collective cases of the disseminated form of this mycosis. Current understanding of the mechanisms of protective immunity against lung infection has been largely derived from murine models of pulmonary coccidioidomycosis. However, little is known about the nature of the host response to Coccidioides in extrapulmonary tissue. Primary subcutaneous coccidioidal infection is rare but has been reported to result in disseminated disease. Here, we show that activation of MyD88 and Card9 signal pathways are required for resistance to Coccidioides infection following subcutaneous challenge of C57BL/6 mice, which correlates with earlier findings of the protective response to pulmonary infection. MyD88(-/-) andCard9(-/-) mice recruited reduced numbers of T cells, B cells, and neutrophils to the Coccidioides-infected hypodermis com pared to wild-type mice; however, neutrophils were dispensable for resistance to skin infection. Further studies have shown that gamma interferon (IFN-γ) production and activation of Th1 cells characterize resistance to subcutaneous infection. Furthermore, activation of a phagosomal enzyme, inducible nitric oxide synthase, which is necessary for NO production, is a requisite for fungal clearance in the hypodermis. Collectively, our data demonstrate that MyD88- and Card9-mediated IFN-γ and nitric oxide production is essential for protection against subcutaneous Coccidioides infection. PMID:26857574

  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. 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

  5. CCAAT/Enhancer-Binding Protein \\(\\gamma\\) Is a Critical Regulator of IL-1\\(\\beta\\)-Induced IL-6 Production in Alveolar Epithelial Cells

    OpenAIRE

    Chunguang Yan; Ximo Wang; Jay Cao; Min Wu; Hongwei Gao

    2012-01-01

    CCAAT/enhancer binding protein \\(\\gamma\\) (C/EBPγ) is a member of the C/EBP family of transcription factors, which lacks known activation domains. C/EBP\\(\\gamma\\) was originally described as an inhibitor of C/EBP transactivation potential. However, previous study demonstrates that C/EBP\\(\\gamma\\) augments the C/EBP\\(\\beta\\) stimulatory activity in lipopolysaccharide induction of IL-6 promoter in a B lymphoblast cell line. These data indicate a complexing functional role for C/EBP\\(\\gamma\\) in...

  6. 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)

  7. Study of Rare B-Meson Decays Related to the CPObservable sin(2beta+gamma) at the BABAR Experiment

    Energy Technology Data Exchange (ETDEWEB)

    Orimoto, Toyoko Jennifer

    2007-08-21

    This study reports the observation of the decays B{sup 0}{yields}D{sup (*)+}{sub S}{pi}{sup -} and B{sup 0}{yields}D{sup (*)-}K{sup +} in a sample of 230 x 10{sup 6} {Upsilon}(4S) {yields} B{bar B} events collected with the BABAR detector at the PEP-II asymmetric-energy e{sup +}e{sup -} storage ring, located at the Stanford Linear Accelerator Center. The branching fractions {beta}(B{sup 0} {yields} D{sup +}{sub S}{pi}{sup -}) = (1.3 {+-} 0.3 (stat) {+-} 0.2 (syst)) x 10{sup -5}, {beta}(B{sup 0} {yields} D{sup +}{sub S}K{sup +}) = (2.5 {+-} 0.4 (stat) {+-} 0.4 (syst)) x 10{sup -5}, {beta}(B{sup 0}{yields}D{sup (*)+}{sub S}{pi}{sup -}) = (2.8 {+-} 0.6 (stat) {+-} 0.5 (syst)) x 10{sup -5}, and {beta}(B{sup 0}{yields}D{sup (*)-}K{sup +}) = (2.0 {+-} 0.5 (stat) {+-} 0.4 (syst)) x 10{sup -5} are measured. The significance of the measurements to differ from zero are 5, 9, 6, and 5 standard deviations, respectively. This is a first observation of the decaysB{sup 0}{yields}D{sup (*)+}{sub S}{pi}{sup -} and B{sup 0}{yields}D{sup (*)-}K{sup +}. These results may potentially be useful in determining the CP asymmetry parameter sin(2{beta} + {gamma}) in the decays B{sup 0}{yields}D{sup (*)+}{sub S}{pi}{sup -}.

  8. The su-bar(2){sub -1/2} WZW model and the {beta}{gamma} system

    Energy Technology Data Exchange (ETDEWEB)

    Lesage, F. E-mail: lesage@crm.umontreal.ca; Mathieu, P. E-mail: pmathieu@phy.ulaval.ca; Rasmussen, J. E-mail: rasmusse@crm.umontreal.ca; Saleur, H. E-mail: saleur@usc.edu

    2002-12-30

    The bosonic {beta}{gamma} ghost system has long been used in formal constructions of conformal field theory. It has become important in its own right in the last few years, as a building block of field theory approaches to disordered systems, and as a simple representative--due in part to its underlying su-bar(2){sub -1/2} structure--of non-unitary conformal field theories. We provide in this paper the first complete, physical, analysis of this {beta}{gamma} system, and uncover a number of striking features. We show, in particular, that the spectrum involves an infinite number of fields with arbitrarily large negative dimensions. These fields have their origin in a twisted sector of the theory, and have a direct relationship with spectrally flowed representations in the underlying su-bar(2){sub -1/2} theory. We discuss the spectral flow in the context of the operator algebra and fusion rules, and provide a re-interpretation of the modular invariant consistent with the spectrum.

  9. Clinical Analysis of Gamma Interferon Combined with Valaciclovir in the Treatment of Recurrent Genital Herpes%γ-干扰素与伐昔洛韦联用有效治疗复发性生殖器疱疹

    Institute of Scientific and Technical Information of China (English)

    宋顼; 孙克红; 周海霞

    2016-01-01

    Objective To investigate the effects of gamma interferon and cut yesterday galloway together clinical curative effect for the treatment of recurrent genital herpes. Methods 64 patients with recurrent genital herpes were randomly divided into two groups, observation group intramuscular gamma interferon 1 million IU, day 1, 20 d Ed;At the same time of oral cutting yesterday 0.3 g, respectively.there 2 times/d, even served 7 d. Control simple oral cutting yesterday galloway. Observe two groups of relapse. Results Observation group recurrence rate significantly lower than the control group ( < 0.05). Conclusion Combination of gamma interferon and cutting yesterday respectively.there is an ideal method to reduce the recurrent genital herpes.%目的探讨γ-干扰素与伐昔洛韦联用治疗复发性生殖器疱疹的临床疗效。方法将64例生殖器疱疹复发患者随机分成两组,观察组肌肉注射γ-干扰素100万IU,隔日1次,连用20d;同时口服伐昔洛韦0.3g,2次/d,连服7d。对照组单纯口服伐昔洛韦,观察两组复发情况。结果观察组复发率明显低于对照组(<0.05)。结论联合使用γ-干扰素与伐昔洛韦是降低生殖器疱疹复发率的理想方法。

  10. Discordance between Frequency of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon-Producing CD4+ T Cells and HIV-1-Specific Lymphoproliferation in HIV-1-Infected Subjects with Active Viral Replication

    OpenAIRE

    Palmer, B. E.; Boritz, E; Blyveis, N.; Wilson, C C

    2002-01-01

    One hallmark of uncontrolled, chronic human immunodeficiency virus type 1 (HIV-1) infection is the absence of strong HIV-1-specific, CD4+ T-cell-proliferative responses, yet the mechanism underlying this T helper (Th)-cell defect remains controversial. To better understand the impact of HIV-1 replication on Th-cell function, we compared the frequency of CD4+ Th-cell responses based on production of gamma interferon to lymphoproliferative responses directed against HIV-1 proteins in HIV-1-infe...

  11. Cytokines downregulate the sarcoendoplasmic reticulum pump Ca2+ ATPase 2b and deplete endoplasmic reticulum Ca2+, leading to induction of endoplasmic reticulum stress in pancreatic beta-cells

    DEFF Research Database (Denmark)

    Cardozo, Alessandra K; Ortis, Fernanda; Storling, Joachim;

    2005-01-01

    , beta-cells showed marked sensitivity to apoptosis induced by SERCA blockers, as compared with fibroblasts. Cytokine-induced ER Ca(2+) depletion was paralleled by an NO-dependent induction of CHOP protein and activation of diverse components of the ER stress response, including activation of inositol......Cytokines and free radicals are mediators of beta-cell death in type 1 diabetes. Under in vitro conditions, interleukin-1beta (IL-1beta) + gamma-interferon (IFN-gamma) induce nitric oxide (NO) production and apoptosis in rodent and human pancreatic beta-cells. We have previously shown......, by microarray analysis of primary beta-cells, that IL-1beta + IFN-gamma decrease expression of the mRNA encoding for the sarcoendoplasmic reticulum pump Ca(2+) ATPase 2b (SERCA2b) while inducing expression of the endoplasmic reticulum stress-related and proapoptotic gene CHOP (C/EBP [CCAAT/enhancer binding...

  12. Monte Carlo Models for the Production of beta-delayed Gamma Rays Following Fission of Special Nuclear Materials

    Energy Technology Data Exchange (ETDEWEB)

    Pruet, J; Prussin, S; Descalle, M; Hall, J

    2004-02-03

    A Monte Carlo method for the estimation of {beta}-delayed {gamma}-ray spectra following fission is described that can accommodate an arbitrary time-dependent fission rate and photon collection history. The method invokes direct sampling of the independent fission yield distributions of the fissioning system, the branching ratios for decay of individual fission products and the spectral distributions for photon emission for each decay mode. Though computationally intensive, the method can provide a detailed estimate of the spectrum that would be recorded by an arbitrary spectrometer, and can prove useful in assessing the quality of evaluated data libraries, for identifying gaps in these libraries, etc. The method is illustrated by a first comparison of calculated and experimental spectra from decay of short-lived fission products following the reactions {sup 235}U(n{sub th}, f) and {sup 239}Pu(n{sub th}, f). For general purpose transport calculations, where detailed consideration of the large number of individual {gamma}-ray transitions in a spectrum may be unnecessary, it is shown that an accurate and simple parameterization of a {gamma}-ray source function can be obtained. These parametrizations should provide high-quality average spectral distributions that should prove useful in calculations describing photons escaping from thick attenuating media.

  13. 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)

  14. Beta and gamma decay heat measurements between 0.1s--50,000s for neutron fission of 235U, 238U and 239Pu

    International Nuclear Information System (INIS)

    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 235U(nthff) 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 235U(nthff) 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 235U(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

  15. CD8+ T-cells expressing interferon gamma or perforin play antagonistic roles in heart injury in experimental Trypanosoma cruzi-elicited cardiomyopathy.

    Science.gov (United States)

    Silverio, Jaline Coutinho; Pereira, Isabela Resende; Cipitelli, Márcio da Costa; Vinagre, Nathália Ferreira; Rodrigues, Maurício Martins; Gazzinelli, Ricardo Tostes; Lannes-Vieira, Joseli

    2012-01-01

    In Chagas disease, CD8(+) T-cells are critical for the control of Trypanosoma cruzi during acute infection. Conversely, CD8(+) T-cell accumulation in the myocardium during chronic infection may cause tissue injury leading to chronic chagasic cardiomyopathy (CCC). Here we explored the role of CD8(+) T-cells in T. cruzi-elicited heart injury in C57BL/6 mice infected with the Colombian strain. Cardiomyocyte lesion evaluated by creatine kinase-MB isoenzyme activity levels in the serum and electrical abnormalities revealed by electrocardiogram were not associated with the intensity of heart parasitism and myocarditis in the chronic infection. Further, there was no association between heart injury and systemic anti-T. cruzi CD8(+) T-cell capacity to produce interferon-gamma (IFNγ) and to perform specific cytotoxicity. Heart injury, however, paralleled accumulation of anti-T. cruzi cells in the cardiac tissue. In T. cruzi infection, most of the CD8(+) T-cells segregated into IFNγ(+) perforin (Pfn)(neg) or IFNγ(neg)Pfn(+) cell populations. Colonization of the cardiac tissue by anti-T. cruzi CD8(+)Pfn(+) cells paralleled the worsening of CCC. The adoptive cell transfer to T. cruzi-infected cd8(-/-) recipients showed that the CD8(+) cells from infected ifnγ(-/-)pfn(+/+) donors migrate towards the cardiac tissue to a greater extent and caused a more severe cardiomyocyte lesion than CD8(+) cells from ifnγ(+/+)pfn(-/-) donors. Moreover, the reconstitution of naïve cd8(-/-) mice with CD8(+) cells from naïve ifnγ(+/+)pfn(-/-) donors ameliorated T. cruzi-elicited heart injury paralleled IFNγ(+) cells accumulation, whereas reconstitution with CD8(+) cells from naïve ifnγ(-/-)pfn(+/+) donors led to an aggravation of the cardiomyocyte lesion, which was associated with the accumulation of Pfn(+) cells in the cardiac tissue. Our data support a possible antagonist effect of CD8(+)Pfn(+) and CD8(+)IFNγ(+) cells during CCC. CD8(+)IFNγ(+) cells may exert a beneficial role

  16. Studies on mechanisms of interferon-gamma action in pancreatic cancer using a data-driven and model-based approach

    Directory of Open Access Journals (Sweden)

    Pöhland Ralf

    2011-02-01

    Full Text Available Abstract Background Interferon-gamma (IFNγ is a multifunctional cytokine with antifibrotic and antiproliferative efficiency. We previously found that pancreatic stellate cells (PSC, the main effector cells in cancer-associated fibrosis, are targets of IFNγ action in the pancreas. Applying a combined experimental and computational approach, we have demonstrated a pivotal role of STAT1 in IFNγ signaling in PSC. Using in vivo and in vitro models of pancreatic cancer, we have now studied IFNγ effects on the tumor cells themselves. We hypothesize that IFNγ inhibits tumor progression through two mechanisms, reduction of fibrogenesis and antiproliferative effects on the tumor cells. To elucidate the molecular action of IFNγ, we have established a mathematical model of STAT1 activation and combined experimental studies with computer simulations. Results In BALB/c-nu/nu mice, flank tumors composed of DSL-6A/C1 pancreatic cancer cells and PSC grew faster than pure DSL-6A/C1 cell tumors. IFNγ inhibited the growth of both types of tumors to a similar degree. Since the stroma reaction typically reduces the efficiency of therapeutic agents, these data suggested that IFNγ may retain its antitumor efficiency in PSC-containing tumors by targeting the stellate cells. Studies with cocultures of DSL-6A/C1 cells and PSC revealed a modest antiproliferative effect of IFNγ under serum-free conditions. Immunoblot analysis of STAT1 phosphorylation and confocal microscopy studies on the nuclear translocation of STAT1 in DSL-6A/C1 cells suggested that IFNγ-induced activation of the transcription factor was weaker than in PSC. The mathematical model not only reproduced the experimental data, but also underscored the conclusions drawn from the experiments by indicating that a maximum of 1/500 of total STAT1 is located as phosphorylated STAT1 in the nucleus upon IFNγ treatment of the tumor cells. Conclusions IFNγ is equally effective in DSL-6A/C1 tumors with and

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

    Directory of Open Access Journals (Sweden)

    Martine G Aabye

    Full Text Available 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 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-IT was positive in 74% (119/161; 95% CI: 67-81%. Sensitivity was higher in HIV-negative (75/93 than in HIV-positive (44/68 patients (81% vs. 65%, p = 0.02 and increased with CD4 cell count in HIV-positive patients (test for trend p = 0.03. 23 patients (14% had an indeterminate result and this proportion decreased with increasing CD4 cell count in HIV-positive patients (test for trend p = 0.03. Low CD4 cell count (<300 cells/microl did not account for all QFT-IT indeterminate nor all negative results. Sensitivity when excluding indeterminate results was 86% (95% CI: 81-92% and did not differ between HIV-negative and HIV-positive patients (88 vs. 83%, p = 0.39. CONCLUSIONS/SIGNIFICANCE: Sensitivity of the QFT-IT for diagnosing active PTB infection was reasonable when excluding indeterminate results and in HIV-negative patients. However, since the test missed more than 10% of patients, its potential as a rule-out test for active TB disease is limited. Furthermore, test performance is impaired by low CD4 cell count in HIV-positive patients and possibly by other factors as well in both HIV-positive and HIV-negative patients. This might limit the potential of the test in populations where HIV-infection is prevalent.

  18. 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.

  19. 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. PMID:26441906

  20. 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

  1. CD8+ T-cells expressing interferon gamma or perforin play antagonistic roles in heart injury in experimental Trypanosoma cruzi-elicited cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Jaline Coutinho Silverio

    Full Text Available In Chagas disease, CD8(+ T-cells are critical for the control of Trypanosoma cruzi during acute infection. Conversely, CD8(+ T-cell accumulation in the myocardium during chronic infection may cause tissue injury leading to chronic chagasic cardiomyopathy (CCC. Here we explored the role of CD8(+ T-cells in T. cruzi-elicited heart injury in C57BL/6 mice infected with the Colombian strain. Cardiomyocyte lesion evaluated by creatine kinase-MB isoenzyme activity levels in the serum and electrical abnormalities revealed by electrocardiogram were not associated with the intensity of heart parasitism and myocarditis in the chronic infection. Further, there was no association between heart injury and systemic anti-T. cruzi CD8(+ T-cell capacity to produce interferon-gamma (IFNγ and to perform specific cytotoxicity. Heart injury, however, paralleled accumulation of anti-T. cruzi cells in the cardiac tissue. In T. cruzi infection, most of the CD8(+ T-cells segregated into IFNγ(+ perforin (Pfn(neg or IFNγ(negPfn(+ cell populations. Colonization of the cardiac tissue by anti-T. cruzi CD8(+Pfn(+ cells paralleled the worsening of CCC. The adoptive cell transfer to T. cruzi-infected cd8(-/- recipients showed that the CD8(+ cells from infected ifnγ(-/-pfn(+/+ donors migrate towards the cardiac tissue to a greater extent and caused a more severe cardiomyocyte lesion than CD8(+ cells from ifnγ(+/+pfn(-/- donors. Moreover, the reconstitution of naïve cd8(-/- mice with CD8(+ cells from naïve ifnγ(+/+pfn(-/- donors ameliorated T. cruzi-elicited heart injury paralleled IFNγ(+ cells accumulation, whereas reconstitution with CD8(+ cells from naïve ifnγ(-/-pfn(+/+ donors led to an aggravation of the cardiomyocyte lesion, which was associated with the accumulation of Pfn(+ cells in the cardiac tissue. Our data support a possible antagonist effect of CD8(+Pfn(+ and CD8(+IFNγ(+ cells during CCC. CD8(+IFNγ(+ cells may exert a beneficial role, whereas CD8(+Pfn

  2. 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

  3. Role of interferon-gamma release assays (IGRAs for the screening of latent tuberculosis infection in patients candidates for TNF-α antagonist

    Directory of Open Access Journals (Sweden)

    Ilaria Sauzullo

    2010-06-01

    Full Text Available Background: Tumor necrosis factor-α (TNF-a inhibitors are associated with an increased risk of reactivation of latent tuberculosis infection (LTBI; thus, the guidelines recommends TB screening for all patients before starting anti-TNF-α therapy.The use of tuberculin skin test (TST is controversial because of the immunosuppressive treatment may lead to false-negative TST results and previous BCG-vaccination produces false-positive. The introduction in clinical practice of the interferon-gamma release assays (IGRAs has opened new perspectives for diagnosis of LTBI.The aim of the study was to investigate the performance of QuantiFERON-TB Gold In Tube assay (QFT-GIT for the diagnosis of LTBI in patients with an immune-mediated inflammatory diseases candidates for anti-TNF-α therapy. Methods:We enrolled 195 patients with rheumatoid arthritis (n=72, psoriatic arthritis (n=40, psoriasis (n=41, ankylosing spondylitis (n=10, Crohn’s disease (n=18, and Behcet’s disease (n=8. Screening included: clinical evaluation, chest X-ray,TST and QFT-GIT. Results: Of the 195 patients, 32 (16.4%, 137 (70.2% and 26 (13.3% tested positive, negative and indeterminate with QFT-GIT test, respectively. The level of agreement between two tests was 81.6 % (k=0.55. Among the screened patients, 38 (19% were considered to have LTBI and received isoniazid treatment, while 31 patients (16% showed discordant results between two tests. Univariate analysis showed an association between BCG vaccination and discordant TST-positive/QFT-GIT-negative results (OR=6; 95%CI: 2.3-37.1; p<0.001; no association was observed between the immunosuppressive therapy and discordant TST-negative/QFT-GIT-positive results (OR=0.16; 95%CI: 0.01-1.8; p<0.09. Conclusions: Our results suggest that QFT-GIT may be helpful for the diagnosis of LTBI in patients candidates for anti-TNF-α treatment because of its performance seems to not be affected by any type of immunosuppression.

  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. Infrared Zero of $\\beta$ and Value of $\\gamma_m$ for an SU(3) Gauge Theory at the Five-Loop Level

    CERN Document Server

    Ryttov, Thomas A

    2016-01-01

    We calculate the value of the coupling at the infrared zero of the beta function of an asymptotically free SU(3) gauge theory at the five-loop level as a function of the number of fermions. Both a direct analysis of the beta function and analyses of Pad\\'e approximants are used for this purpose. We then calculate the value of the five-loop anomalous dimension, $\\gamma_m$, of the fermion bilinear at this IR zero of the beta function.

  6. γ-干扰素和白介素抗弓形虫感染研究进展%Advances in the study of interferon-gamma and interleukin in Toxoplasma gondii infection

    Institute of Scientific and Technical Information of China (English)

    聂大平; 李伟; 申丽洁; 尤英霞

    2012-01-01

    Toxoplasma gondii is a protozoan parasite of nucleated cells that can infect nearly all warm-blooded animals, including humans, and cause serious zoonosis in the form of toxoplasmosis. Gamma-interferon and interleukin levels in the host's body affect the vertical transmission of T. gondii and determine the development and prognosis of toxoplasmosis. These cytokincs play an important role in the host's resistance to T. gondii infection. This article reviews advances in gamma-interferon and interleukins to fight T. gondii infection%刚地弓形虫(Toxoplasma gondii)是一种专性有核细胞内寄生虫,可以感染包括人类在内的几乎所有温血动物,能引起严重的人兽共患弓形虫病.宿主体内γ-干扰素和白介素的水平影响弓形虫的垂直传播并决定弓形虫病的发生与转归,γ-干扰素和白介素在宿主抗弓形虫感染中有着重要的作用.本文对γ-干扰素和白介素抗弓形虫感染研究进展进行了综述.

  7. Beta-delayed gamma and proton spectroscopy near the Z=N line

    Energy Technology Data Exchange (ETDEWEB)

    Kankainen, A.; Eronen, T.; Hager, U.; Hakala, J.; Huang, W.; Huikari, J.; Jokinen, A.; Kopecky, S.; Moore, I.; Nieminen, A.; Penttilae, H.; Rinta-Antila, S.; Wang, Y.; Aeystoe, J. [University of Jyvaeskylae, Department of Physics, P.O. Box 35, Jyvaeskylae (Finland); Eliseev, S.A. [Petersburg Nuclear Physics Inst. (Russian Federation); GSI, Darmstadt (Germany); Fox, S.P.; Jenkins, D. [University of York, Department of Physics, Heslington (United Kingdom); Novikov, Yu.N.; Vorobjev, G.K. [Petersburg Nuclear Physics Inst. (Russian Federation); St. Petersburg Univ. (Russian Federation); Popov, A.V.; Seliverstov, D.M. [Petersburg Nuclear Physics Institute, Petersburg (Russian Federation); Schatz, H. [Michigan State University, East Lansing, MI (United States)

    2005-09-01

    A series of beta decay experiments on nuclei near the Z=N line has been performed using the ISOL technique at the IGISOL facility in Jyvaeskylae and at ISOLDE, CERN. The decay properties of these neutron-deficient nuclei are important in astrophysics as well as in the studies of isospin symmetry. (orig.)

  8. Interferon Analogs

    NARCIS (Netherlands)

    Poelstra, Klaas; Prakash, Jai; Beljaars, Eleonora; Bansal, Ruchi

    2015-01-01

    The invention relates to the field of medicine. Among others, it relates to biologically active analogs of interferons (IFNs) which show less unwanted side-effects and to the therapeutic uses thereof. Provided is an IFN analog, wherein the moiety mediating binding to its natural receptor is at least

  9. Interferon Analogs

    NARCIS (Netherlands)

    Poelstra, Klaas; Prakash, Jai; Beljaars, Leonie; Bansal, Ruchi

    2010-01-01

    The invention relates to the field of medicine. Among others, it relates to biologically active analogs of interferons (IFNs) which show less unwanted side-effects and to the therapeutic uses thereof. Provided is an IFN analog, wherein the moiety mediating binding to its natural receptor is at least

  10. Sub-millimeter nuclear medical imaging with reduced dose application in positron emission tomography using beta-gamma coincidences

    CERN Document Server

    Lang, C; Parodi, K; Thirolf, P G

    2013-01-01

    Positron emission tomography (PET) permits a functional understanding of the underlying causes of many diseases. Modern whole-body PET systems reach a spatial resolution of 2-6 mm (FWHM). A limitation of this technique occurs from the thermalization and diffusion of the positron before its annihilation, typically within the mm range. We present a nuclear medical imaging technique, able to reach sub-millimeter spatial resolution in 3 dimensions with a reduced effective dose application compared to conventional PET. This 'gamma-PET' technique draws on specific medical isotopes, simultaneously emitting an additional photon accompanying the beta^+ decay. Exploiting the triple coincidence between the positron annihilation and the third photon, it is possible to separate the reconstructed 'true' events from background. In order to characterize the potential of this technique, MC simulations and image reconstructions have been performed. The achievable spatial resolution has been found to reach ca. 0.4 mm (FWHM) in ...

  11. Sugar derivatives containing oxiranes and alpha,beta-unsaturated gamma-lactones as potential environmentally friendly insecticides.

    Science.gov (United States)

    Justino, Jorge; Rauter, Amélia P; Canda, Tana; Wilkins, Richard; Matthews, Elizabeth

    2005-10-01

    A range of novel sugar derivatives containing oxiranes or alpha,beta-unsaturated gamma-lactones in their structure were evaluated as potential insecticides with the added possible benefit of being benign in the environment. A number of arthropod species were chosen to represent those in the terrestrial, aerial and aquatic environments, covering target adult insects such as Musca domestica L (housefly) and Trialeurodes vaporariorum (Westwood) (glasshouse whitefly), which are public health and horticultural pests, Drosophila melanogaster Meig (fruitfly), both adult and larva, and a marine non-target crustacean, Artemia salina L. The tested compounds possessed efficacy and selectivity against these insect species, but were not toxic to brine shrimps, a reference organism in assays to evaluate the potential toxicity hazard to invertebrates in ecosystems.

  12. Diffusion of uranium at infinite dilution in {beta}-titanium and {gamma}-iron; Diffusion de l'uranium en dilution infinie dans le titane {beta} et le fer {gamma}

    Energy Technology Data Exchange (ETDEWEB)

    Keroulas, F. de [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1967-02-15

    We describe a method based on the recording of fission fragments in insulators allowing the study of uranium concentrations in metals about 10{sup 4} to 10{sup 5} lower than those possible by autoradiography of {sup 235}U. This method has been used to study the diffusion of uranium (concentration between 10{sup -7} and 10{sup -8}) in {beta} titanium and in {gamma} iron. The diffusion coefficient obey the equation: D = D{sub 0} exp (- H/kT) with D{sub 0} = 2.10{sup -3} cm{sup 2} s{sup -1} and H = 1,43 eV/ at. for titanium and D{sub 0} = 7.10{sup -5} cm{sup 2} s{sup -1} and H = 1,38 eV/ at. for iron In titanium there is a distinct increment of diffusion when the allotropic transformation is reached; it appears to be due to the point defects created by the transformation. (author) [French] On decrit une methode, fondee sur l'enregistrement des fragments de fission dans les isolants, permettant d'etudier dans les metaux des concentrations d'uranium d'environ 10{sup 4} a 10{sup 5} fois inferieures a celles que permet l'autoradiographie de {sup 235}U. La methode a ete appliquee a l'etude de la diffusion de l'uranium (en concentration comprise entre 10{sup -7} et 10{sup -8} ) dans le titane {beta} et dans le fer {gamma}. Les coefficients de diffusion obeissent a l'equation D = D{sub 0} exp (- H/kT) avec D{sub 0} = 2.10{sup -3} cm{sup 2} s{sup -1} et H = 1,43 eV/ at. pour le titane et D{sub 0} = 7.10{sup -5} cm{sup 2} s{sup -1} et H = 1,38 eV/ at. pour le fer Dans le cas du titane, le passage du point de transformation {beta} ->{alpha} provoque une migration notable qui semble due aux defauts ponctuels crees par la transformation. (auteur)

  13. 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

  14. Phenotypic consequences of deletion of the {gamma}{sub 3}, {alpha}{sub 5}, or {beta}{sub 3} subunit of the type A {gamma}-aminobutyric acid receptor in mice

    Energy Technology Data Exchange (ETDEWEB)

    Culia, C.T.; Stubbs, L.J.; Montgomery, C.S.; Russell, L.B.; Rinchik, E.M. [Oak Ridge National Lab., TN (United States)

    1994-03-29

    Three genes (Gabrg3, Gabra5, and Gabrb3) encoding the {gamma}{sub 3}, {alpha}{sub 5}, and {beta}{sub 3} subunits of the type A {gamma}-aminobutyric acid receptor, respectively, are known to map near the pink-eyed dilution (p) locus in mouse chromosome 7. This region shares homology with a segment of human chromosome 15 that is implicated in Angelman syndrome, an inherited neurobehavioral disorder. By mapping Gabrg3-Gabra5-Gabrb3-telomere. Like Gabrb3, neither the Gabra5 nor Gabrg3 gene is functionally imprinted in adult mouse brain. Mice deleted for all three subunits die at birth with a cleft palate, although there are rare survivors ({approximately} 5%) that do not have a cleft palate but do exhibit a neurological abnormality characterized by tremor, jerky gait, and runtiness. The authors have previously suggested that deficiency of the {beta}{sub 3} subunit may be responsible for the clefting defect. Most notably, however, in this report they describe mice carrying two overlapping, complementing p deletions that fail to express the {gamma}{sub 3} transcript, as well as mice from another line that express neither the {gamma}{sub 3} nor {alpha}{sub 5} transcripts. Surprisingly, mice from both of these lines are phenotypically normal and do not exhibit any of the neurological symptoms characteristic of the rare survivors that are deleted for all three ({gamma}{sub 3}, {alpha}{sub 5}, and {beta}{sub 3}) subunits. These mice therefore provide a whole-organism type A {gamma}-aminobutyric-acid receptor background that is devoid of any receptor subtypes that normally contain the {gamma}{sub 3} and/or {alpha}{sub 5} subunits. The absence of an overt neurological phenotype in mice lacking the {gamma}{sub 3} and/or {alpha}{sub 5} subunits also suggests that mutations in these genes are unlikely to provide useful animal models for Angelman syndrome in humans.

  15. Behaviour of {alpha}-, {beta}-, {gamma}-, and {delta}-hexachlorocyclohexane in the soil-plant system of a contaminated site

    Energy Technology Data Exchange (ETDEWEB)

    Calvelo Pereira, R. [Departamento de Edafoloxia e Quimica Agricola, Facultade de Bioloxia, Universidade de Santiago de Compostela, 15782-Santiago de Compostela (Spain)]. E-mail: edrobert@usc.es; Camps-Arbestain, M. [Departamento de Edafoloxia e Quimica Agricola, Facultade de Bioloxia, Universidade de Santiago de Compostela, 15782-Santiago de Compostela (Spain); Rodriguez Garrido, B. [Departamento de Edafoloxia e Quimica Agricola, Facultade de Bioloxia, Universidade de Santiago de Compostela, 15782-Santiago de Compostela (Spain); Macias, F. [Departamento de Edafoloxia e Quimica Agricola, Facultade de Bioloxia, Universidade de Santiago de Compostela, 15782-Santiago de Compostela (Spain); Monterroso, C. [Departamento de Edafoloxia e Quimica Agricola, Facultade de Bioloxia, Universidade de Santiago de Compostela, 15782-Santiago de Compostela (Spain)

    2006-11-15

    The behaviour of the organochlorine pesticide hexachlorocyclohexane (HCH) is investigated. The concentrations of {alpha}-, {beta}-, {gamma}-, and {delta}-HCH isomers were measured in soils, rhizosphere and vegetation in a contaminated area in Galicia (NW Spain). The total concentration of HCH in soils reached values close to 20 000 mg kg{sup -1}. The plants analysed (Avena sativa L., Chenopodium spp., Solanum nigrum L., Cytisus striatus (Hill) Roth, and Vicia sativa L.) accumulated HCH, especially the {beta}-HCH isomer, in their tissues. The most likely mechanisms of HCH accumulation in plants were sorption of soil HCH on roots and sorption of volatilized HCH on aerial plant tissues. The concentrations of HCH obtained from the bulk and rhizosphere soils of selected plant species suggest that roots tend to reduce levels of the HCH isomers in the rhizosphere. The results reflect the importance of vegetation in the distribution of organochlorine compounds in the soil-plant system. - This paper describes the soil-plant relationship of hexachlorocyclohexane isomers in a contaminated site, with special focus on the rhizosphere effect.

  16. Search for 2\\beta\\ decays of 96Ru and 104Ru by ultra-low background HPGe gamma spectrometry at LNGS: final results

    CERN Document Server

    Belli, P; Cappella, F; Cerulli, R; Danevich, F A; d'Angelo, S; Incicchitti, A; Kovtun, G P; Kovtun, N G; Laubenstein, M; Poda, D V; Polischuk, O G; Shcherban, A P; Solopikhin, D A; Suhonen, J; Tretyak, V I

    2013-01-01

    An experiment to search for double beta decay processes in 96Ru and 104Ru, which are accompanied by gamma rays, has been realized in the underground Gran Sasso National Laboratories of the I.N.F.N. (Italy). Ruthenium samples with masses of about (0.5-0.7) kg were measured with the help of ultra-low background high purity Ge gamma ray spectrometry. After 2162 h of data taking the samples were deeply purified to reduce the internal contamination of 40K. The last part of the data has been accumulated over 5479 h. New improved half life limits on 2\\beta+/\\epsilon \\beta+/2\\epsilon\\ processes in 96Ru have been established on the level of 10^{20} yr, in particular for decays to the ground state of 96Mo: T1/2(2\

  17. Immunocytochemical localization of latent transforming growth factor-beta1 activation by stimulated macrophages

    Science.gov (United States)

    Chong, H.; Vodovotz, Y.; Cox, G. W.; Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

    1999-01-01

    Transforming growth factor-beta1 (TGF-beta) is secreted in a latent form consisting of mature TGF-beta noncovalently associated with its amino-terminal propeptide, which is called latency associated peptide (LAP). Biological activity depends upon the release of TGF-beta from the latent complex following extracellular activation, which appears to be the key regulatory mechanism controlling TGF-beta action. We have identified two events associated with latent TGF-beta (LTGF-beta) activation in vivo: increased immunoreactivity of certain antibodies that specifically detect TGF-beta concomitant with decreased immunoreactivity of antibodies to LAP. Macrophages stimulated in vitro with interferon-gamma and lipopolysaccharide reportedly activate LTGF-beta via cell membrane-bound protease activity. We show through dual immunostaining of paraformaldehyde-fixed macrophages that such physiological TGF-beta activation is accompanied by a loss of LAP immunoreactivity with concomitant revelation of TGF-beta epitopes. The induction of TGF-beta immunoreactivity colocalized with immunoreactive betaglycan/RIII in activated macrophages, suggesting that LTGF-beta activation occurs on the cell surface. Confocal microscopy of metabolically active macrophages incubated with antibodies to TGF-beta and betaglycan/RIII prior to fixation supported the localization of activation to the cell surface. The ability to specifically detect and localize LTGF-beta activation provides an important tool for studies of its regulation.

  18. Cytokines in relapsing experimental autoimmune encephalomyelitis in DA rats: persistent mRNA expression of proinflammatory cytokines and absent expression of interleukin-10 and transforming growth factor-beta

    DEFF Research Database (Denmark)

    Issazadeh-Navikas, Shohreh; Lorentzen, J C; Mustafa, M I;

    1996-01-01

    ) of diseased DA rats. We demonstrate that peripheral lymphoid cells stimulated in vitro with encephalitogenic peptides 69-87 and 87-101 of myelin basic protein responded with high mRNA expression for proinflammatory cytokines; interferon-gamma, interleukin-12 (IL-12), tumour necrosis factors alpha and beta, IL...

  19. Effect of neuropeptide Y on white matter demyelination and serum interleukin-4 and gamma-interferon levels in the guinea pig with experimental allergic encephalomyelitis

    Institute of Scientific and Technical Information of China (English)

    Xiaohong Li; Ke Yu; Zuoxiao Li

    2008-01-01

    BACKGROUND: Neuropeptide Y (NPY) may influence differentiation of Th cells. It is assumed that the immunological pathology of experimental allergic encephalomyelitis (EAE) is related to abnormal differentiation of Th cellsOBJECTIVE: To investigate the effect of NPY on white matter demyelination, the serum levels interleukin-4 (IL-4) and gamma-interferon (IFN-γ), as well as EAE pathogenesis in an EAE guinea pig model following NPY injection into the lateral cerebral ventricle.DESIGN, TIME AND SETTING: A randomized controlled animal study, which was performed in the Infection Immunity Animal Laboratory, Affiliated Hospital of Luzhou Medical College, China, from October 2005 to April 2006.MATERIALS: Thirty healthy female guinea pigs of 8-12 weeks of age, and 10 healthy female rats of three months of age were used. NPY was provided by Sigma Company, USA. NPY kit was provided by Beijing Huaying Biotechnology Institute, China.METHODS: Thirty guinea pigs were randomly divided into three groups: normal control group, EAE model group, and NPY intervention group (n=10 per group). Normal control group and EAE model group: Saline (10μL, once) was injected into the lateral cerebral ventricle. After one week, the same volume of Freund's adjuvant complete was either injected subcutaneously into two post-palms or EAE was modeled. NPY intervention group: EAE was modeled after one week and NPY was injected (10μL of 6nmol NPY, once) into the lateral cerebral ventricle. Myelin basic protein (MBP) antigen made from rat spinal cord homogenate and Freund's adjuvant complete were injected subcutaneously into both post-palms (0.2mL per palm) to establish the EAE model.MAIN OUTCOME MEASURES: White matter demyelination of the cerebrum, cerebellum, brain stem, and spinal cord were observed by light microscopy after HE staining. Levels of serum IFN-γ and IL-4 were detected by the double antibody sandwich ABC-ELISA technique. NPY content was detected by radioimmunoassay

  20. 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.