Sample records for beta interferon gamma

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

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


    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

    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

    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 Beta-1a Intramuscular Injection

    Interferon beta-1a intramuscular injection is used to reduce the number of episodes of symptoms and slow ... and problems with vision, speech, and bladder control). Interferon beta-1a is in a class of medications ...

  5. Interferon Beta-1a Subcutaneous Injection

    Interferon beta-1a subcutaneous injection is used to reduce episodes of symptoms and slow the development of ... and problems with vision, speech, and bladder control). Interferon beta-1a is in a class of medications ...

  6. Interferon Beta-1a Intramuscular Injection

    Interferon beta-1a intramuscular injection is used to reduce the number of episodes of symptoms and slow the development of disability in patients ... Interferon beta-1a intramuscular injection comes as a powder in vials to be mixed into a solution for injection. Interferon beta-1a intramuscular ...

  7. Inhibition of 125I-epidermal growth factor binding to cultured keratinocytes by antiproliferative molecules gamma interferon, cyclosporin A, and transforming growth factor-beta

    The growth of cultured human keratinocytes (KC) is inhibited by gamma interferon (IFN-gamma), cyclosporin A and transforming growth factor-beta, but not by tumor necrosis factor. When these antiproliferative molecules were added to KC they induced a concentration and time-dependent inhibition of 125I-epidermal growth factor (I-EGF) binding. These anti-proliferative molecules primarily reduced the number of binding sites by approximately 25%-50% without affecting the binding affinity. Tumor necrosis factor did not influence the ligand binding by I-EGF. In parallel with the ability of the antiproliferative molecules to inhibit I-EGF binding, there was an increase in transforming growth factor-alpha production. These results suggest that several different antiproliferative molecules may share a common mechanism to inhibit cell growth by reducing I-EGF binding to KC

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

    Johnson, H M; Torres, B A


    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...

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

    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.


    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

  10. Beta and Gamma Gradients

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


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

  11. Simultaneous beta and gamma spectroscopy

    Farsoni, Abdollah T.; Hamby, David M.


    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.

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

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


    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.

  13. Beta-gamma discriminator circuit

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

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


    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

  15. Beta-interferon inhibits cell infection by Trypanosoma cruzi

    Kierszenbaum, F.; Sonnenfeld, G.


    Beta interferon has been shown to inhibit the capacity of bloodstream forms of the flagellate Trypanosoma cruzi, the causative agent of Chagas' disease, to associate with and infect mouse peritoneal macrophages and rat heart myoblasts. The inhibitory effect was abrogated in the presence of specific antibodies to the interferon. Pretreatment of the parasites with interferon reduced their infectivity for untreated host cells, whereas pretreament of either type of host cell did not affect the interaction. The effect of interferon on the trypanosomes was reversible; the extent of the inhibitory effect was significantly reduced afer 20 min, and was undetectable after 60 min when macrophages were used as host cells. For the myoblasts, 60 min elapsed before the inhibitory effect began to subside and 120 min elapsed before it became insignificant or undetectable.

  16. Recombinant interferon-gamma (rIFN-gamma) in dermatology.

    Mahrle, G; Schulze, H J


    This paper gives a short review on the function, pharmacokinetics, and therapeutic application of recombinant interferon-gamma (rIFN-gamma) in dermatology. Simultaneously, our own experiences are presented for 57 patients (phase II study) suffering from genital warts (21 patients), psoriatic arthritis (10 patients), psoriasis vulgaris (three patients), malignant melanoma (six patients), bowenoid papulosis (four patients), Behcet's disease (four patients), basal cell carcinoma (six patients), as well as herpes simplex recidivans, epidermodysplasia verruciformis, and mycosis fungoides (one patient each). We conclude that there might be an indication for treatment with rIFN-gamma in genital warts, bowenoid papulosis, Behcet's disease, and microbial infections, such as leprosy and cutaneous leishmaniasis. Even though there are reports of a limited beneficial effect of rIFN-gamma on arthritis and skin lesions in psoriasis, we failed to observe any in 10 patients. The main side effects in our low-dose study (50-100 micrograms/d) were mild fever (78%), fatigue (78%), and myalgia (65%). Laboratory tests revealed an increase in the serum triglyceride level, in particular, in psoriatic patients. PMID:2124242

  17. Antibodies against interferon-beta in neuromyelitis optica patients

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


    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...

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

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


    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...

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

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


    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...

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

    Lyons, Anthony


    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.

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

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


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

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

    Krakauer, Martin


    inflammation or secondary lymphatic organs. Chemokine receptors are differentially expressed in T cells in blood and cerebrospinal fluid, indicating their role for in T-cell-recruitment to the CNS. Interferon (IFN)-beta is a first-line treatment for MS. The mechanism of action is unclear, but probably includes...... changes in lymphocyte activation, cytokine secretion, and trafficking. The aim of the studies was to shed more light on T-cell immunology in MS and IFN-beta treatment, as well as identifying putative biomarkers of treatment response and/or disease activity. In one study we identified a Th-cell subset of...

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

    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...

  4. Interferon-gamma confers resistance to experimental allergic encephalomyelitis

    Krakowski, M; Owens, T


    In experimental allergic encephalomyelitis (EAE), T cells infiltrate the central nervous system (CNS) and induce inflammation. These CD4+ T cells secrete interferon (IFN)-gamma, levels of which correlate with disease severity, and which is proposed to play a key role in disease induction. Many st...... the spinal cord. We thus demonstrate that lack of IFN-gamma converts an otherwise EAE-resistant mouse strain to become susceptible to disease. Therefore, in BALB/c mice, IFN-gamma confers resistance to EAE.......In experimental allergic encephalomyelitis (EAE), T cells infiltrate the central nervous system (CNS) and induce inflammation. These CD4+ T cells secrete interferon (IFN)-gamma, levels of which correlate with disease severity, and which is proposed to play a key role in disease induction. Many...... severity in mice lacking IFN-gamma. Immunological characteristics of disease in IFN-gamma-deficient mice were comparable to those seen in susceptible (SJL/J) mice with EAE, including perivascular infiltration in the CNS and order-of-magnitude increases for both CD3 gamma chain and TNF-alpha mRNA levels in...

  5. Simultaneous beta/gamma digital spectroscopy

    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.

  6. 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

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


    proliferation and insulin production in pancreatic beta-cells and rat insulin-producing INS-1 cells. Here we report that human (h) GH can prevent the apoptotic effects of IL-1beta, IFN-gamma and TNF-alpha in INS-1 and INS-1E cells. Using adenovirus-mediated gene transfer, we found that the anti-apoptotic effect...... expression and in fact augmented the IL-1beta-stimulated nitric oxide production. As the anti-apoptotic Bcl-xL gene has been shown to harbour a STAT5-binding element we measured the expression of Bcl-xL as well as the pro-apoptotic Bax. We found that hGH increased the Bcl-xL/Bax ratio both in the absence and...

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

    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...

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

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


    We describe the performance of cell-based and antibody blood tests for the antemortem diagnosis of tuberculosis (TB) in South American camelids (SAC). The sensitivity and specificity of the gamma interferon (IFN-γ) release assay, two lateral flow rapid antibody tests (Stat-Pak and Dual Path Platform [DPP]), and two enzyme-linked immunosorbent assay (ELISA)-based antibody tests (Idexx and Enferplex) were determined using diseased alpacas from Mycobacterium bovis culture-confirmed breakdown her...

  9. 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

    Issazadeh-Navikas, Shohreh; Mustafa, M; Ljungdahl, A; Höjeberg, B; Dagerlind, A; Elde, R; Olsson, T


    spinal cord with no clear relation to clinical signs or histopathology. In contrast, expression of mRNA for TGF-beta did not increase until day 13 p.i., at height of the disease, shortly preceding recovery. These data are consistent with a disease upregulating role of IFN-gamma, while TGF-beta may act to......-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......, the target organ in EAE, cells expressing mRNA for IFN-gamma, first appeared at the onset of clinical signs, i.e., day 10 postimmunization (p.i.), peaked at the height of disease (day 13 p.i.) and then gradually decreased concomitant with recovery. Very few IL-4 mRNA-expressing cells appeared in the...

  10. Expression of ovine gamma interferon in Escherichia coli and Corynebacterium glutamicum.

    Billman-Jacobe, H; Hodgson, A L; Lightowlers, M; Wood, P. R.; Radford, A J


    Bacteria of two species, Escherichia coli and Corynebacterium glutamicum, were used as hosts to express recombinant ovine gamma interferon as a fusion protein with glutathione S-transferase. The recombinant gamma interferon produced by both bacteria was biologically active in vitro and was recognized by anti-gamma interferon monoclonal antibodies. E. coli produced large amounts of soluble recombinant protein which could be purified by a simple affinity chromatography method. Only a small frac...

  11. Influence of recombinant bovine gamma interferon on neutrophil function

    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

  12. Computer simulations of human interferon gamma mutated forms

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


    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.

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

    Haji Abdolvahab, M.


    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

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

    Hokland, M; Heron, I; Berg, K


    Normal human peripheral blood lymphocytes were incubated in the presence of different concentrations of interferon for various incubation periods. Subsequently, the amount of beta 2-Microglobulin and HLA-A, B and C surface antigens was estimated by means of quantitative immunofluorescence (flow...... cytofluorometry) and by a radioimmunoassay for beta 2-Microglobulin. It was found that the amounts of these MHC antigens increased in a dose and time-dependent way after interferon treatment. Furthermore, the influence of different temperatures on this IFN-induced increase in beta 2-Microglobulin was gradually...... enhanced after incubation at 37 degrees C to 39 degrees C incubation mostly suppressed the beta 2-Microglobulin increase observed at 39 degrees C. The total amount of membrane associated beta 2-Microglobulin was estimated by a radioimmunoassay. After interferon treatment a beta 2-Microglobulin increase...

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

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


    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....

  16. 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

    韩猛立; 黄新; 钟发刚


    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。

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

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


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


    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.

  19. Beta/gamma test problems for ITS

    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. [Phase I-II study of recombinant interferon gamma].

    Adachi, K; Ogawa, M; Usui, N; Inagaki, J; Horikoshi, N; Inoue, K; Nakada, H; Tada, A; Yamazaki, H; Mukaiyama, T


    A phase I-II study of human recombinant interferon gamma (rIFN-gamma) was conducted in patients with various advanced cancer refractory to standard chemotherapies. In the phase I study, seven patients received 14 courses of escalating doses ranging from 2 X 10(6)U/m2 to 64 X 10(6)U/m2 by 1-hour intravenous infusion for 5 consecutive days. The toxicities were high fever with chills, anorexia, occasional nausea and vomiting, elevation of serum GOT, and dose-related leukopenia and neurotoxic symptoms such as heavy fatigue with somnolence or lethargy, both of which were reversible. The pharmacokinetics showed that the peak levels of serum rIFN-gamma activity were dose-related but decreased rapidly to below measurable levels within 6 hours after infusion in patients receiving less than 12 X 10(6)U/m2. Considering these data, the dosage of rIFN-gamma 6 X 10(6) U/m2 by daily intramuscular injection for more than 4 weeks was selected for the early phase II study. There was no partial response out of 11 evaluable patients but a stable condition was observed in 2 cases of renal cell carcinoma and one case each of breast cancer and ovarian cancer. All toxicities seen were similar to those observed in the phase I study, but no tachyphylaxis developed with continued dosage. The antitumor effect of rIFN-gamma remains to be evaluated in a further study employing higher doses. PMID:2988459

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

    Heron, I; Hokland, M; Berg, K


    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...... immunofluorescence (fluorescence-activated cell sorter) and by the capacity of cells to absorb out cytotoxic antibodies against the relevant antigens. Interferons of different origin and purities enhanced the expression of HLA antigens and beta(2)-microglobulins, whereas membrane immunoglobulins and antigens...... recognized by antiserum raised against human brain and T cells were the same on interferon-treated and control cells. Similar interferon effects were observed on an Epstein-Barrvirus-negative Burkitt lymphoma cell line. The enhanced expression of histocompatibility antigen subsequent to intereferon treatment...

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

    Marziniak, Martin; Meuth, Sven


    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...

  3. Comparison of Tuberculin Activity in the Interferon-gamma Assay for the Diagnosis of Bovine Tuberculosis

    Cattle infected with bovine tuberculosis still represent a serious regulatory and health concern in a variety of countries. Early diagnosis using the in vitro interferon gamma (IFN-gamma) assay has been applied for more than a decade. Briefly, IFN-gamma responses in whole blood cultures stimulated w...

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

    Horvat, R T; Parmely, M J


    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...

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

    Mahe J


    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

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

    Magyari, M; Koch-Henriksen, N; Laursen, B; Sørensen, P S


    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...

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

    Full Text Available 18163952 The interferon signaling network and transcription factor C/EBP-beta. Li H..., Gade P, Xiao W, Kalvakolanu DV. Cell Mol Immunol. 2007 Dec;4(6):407-18. (.png) (.svg) (.html) (.csml) Show The... interferon signaling network and transcription factor C/EBP-beta. PubmedID 18163952 Title The interfero

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

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


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

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


    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

  10. Recombinant human interferon gamma in the treatment of rheumatoid arthritis: double blind placebo controlled study.

    Machold, K P; Neumann, K.; Smolen, J.S.


    Interferon gamma (IFN gamma) has been advocated in open studies as a beneficial remission inducing drug for the treatment of rheumatoid arthritis (RA). The work reported here was designed to assess the therapeutic potential of IFN gamma in the treatment of RA in a double blind placebo controlled study. It was found that patients treated with IFN gamma improved significantly with respect to morning stiffness, grip strength, swelling of an index joint, and erythrocyte sedimentation rate. Furthe...

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

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


    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...

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

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


    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.

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

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

    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 r...

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

    Arai Hajime


    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.

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

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


    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...

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

    Edan, G; Kappos, L; Montalbán, X;


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

  17. Patient satisfaction with the BETACONNECT™ autoinjector for interferon beta-1b

    Weller I


    Full Text Available Ivonne Weller,1 Anna Saake,1 Thomas Schreiner,1 Julika Vogelreuter,1 Nicolas Petroff2 1Bayer Vital GmbH, Leverkusen, Germany; 2Vitartis Medizin-Service GmbH, Göttingen, Germany Purpose: Multiple sclerosis (MS is a chronic demyelinating, degenerative disease requiring long-term treatment. Patient adherence to treatment may be challenging in such scenarios, especially since treatment often involves self-injection, for example, with interferon beta-1b during therapy. BETACONNECT™ is a novel electronic autoinjector for patient support in interferon beta-1b administration. The purpose of this survey was to assess patient satisfaction with the BETACONNECT™ device and its features.Patients and methods: A total of 2,299 MS patients using the BETACONNECT™ device were asked to participate in a survey in October 2014. All of these candidates participated in the BETAPLUS® program and had provided written informed consent. The participants were asked to answer 13 device-related questions.Results: Of these candidates, 1,365 replied to the questionnaire, with more than 60% of the participants being 40–59 years of age. Among them, 69% were women and 21% were men (10% not specified. Approximately half of the participants received treatment with interferon beta-1b for more than 5 years. Most participants (85% had used self-injection devices before, with 59% previously using BETACOMFORT®, 23% using BETAJECT® Comfort, and 3% using BETAJECT® Lite, while less than 4% manually injected interferon beta-1b. The majority of the participants had received the BETACONNECT™ device from a BETAPLUS® nurse (87% and 48% had already used the device for more than 2 months (49% for 2 months or less. Among the participants, more than 90% evaluated the BETACONNECT™ device as “very helpful” or “helpful” in supporting their interferon beta-1b therapy with only marginal sex differences. Features that were rated “very important” by more than half of the

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

    Polman, Chris H; Bertolotto, Antonio; Deisenhammer, Florian; Giovannoni, Gavin; Hartung, Hans-Peter; Hemmer, Bernhard; Killestein, Joep; McFarland, Henry F; Oger, Joel; Pachner, Andrew R; Petkau, John; Reder, Anthony T; Reingold, Stephen C; Schellekens, Huub; Sørensen, Per Soelberg


    in MS and NAbs to interferon-beta therapy convened in Amsterdam, Netherlands, under the auspices of the Neutralizing Antibodies on Interferon beta in Multiple Sclerosis consortium, a European-based project of the 6th Framework Programme of the European Commission, to review and discuss data on NAbs...... and their practical consequences for the treatment of patients with MS on interferon beta. The panel believed that information about NAbs and other markers of biological activity of interferons (ie, myxovirus resistance protein A [MxA]) can be integrated with clinical and imaging indicators to guide...... individual treatment decisions. In cases of sustained high-titre NAb positivity and/or lack of MxA bioactivity, a switch to a non-interferon-beta therapy should be considered. In patients who are doing poorly clinically, therapy should be switched irrespective of NAb or MxA bioactivity....

  19. Improvements to the BOVIGAM Interferon Gamma (IFN-gamma) Assay for use with Alternative Antigens as Stimulants of Whole Blood Cultures

    The success of bovine tuberculosis eradication programs in many countries have relied on antemortem diagnostic tests measuring cell-mediated immune (CMI) responses such as the tuberculin skin test or the interferon gamma test. The BOVIGAM® interferon gamma (IFN-gamma) test system constitutes a labor...

  20. Blockade of interferon Beta, but not interferon alpha, signaling controls persistent viral infection.

    Ng, Cherie T; Sullivan, Brian M; Teijaro, John R; Lee, Andrew M; Welch, Megan; Rice, Stephanie; Sheehan, Kathleen C F; Schreiber, Robert D; Oldstone, Michael B A


    Although type I interferon (IFN-I) is thought to be beneficial against microbial infections, persistent viral infections are characterized by high interferon signatures suggesting that IFN-I signaling may promote disease pathogenesis. During persistent lymphocytic choriomeningitis virus (LCMV) infection, IFNα and IFNβ are highly induced early after infection, and blocking IFN-I receptor (IFNAR) signaling promotes virus clearance. We assessed the specific roles of IFNβ versus IFNα in controlling LCMV infection. While blockade of IFNβ alone does not alter early viral dissemination, it is important in determining lymphoid structure, lymphocyte migration, and anti-viral T cell responses that lead to accelerated virus clearance, approximating what occurs during attenuation of IFNAR signaling. Comparatively, blockade of IFNα was not associated with improved viral control, but with early dissemination of virus. Thus, despite their use of the same receptor, IFNβ and IFNα have unique and distinguishable biologic functions, with IFNβ being mainly responsible for promoting viral persistence. PMID:25974304

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

    Hedegaard, Chris J; Krakauer, Martin; Bendtzen, Klaus; Sørensen, Per Soelberg; Sellebjerg, Finn; Nielsen, Claus H


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

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

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


    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...

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

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


    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).

  4. [Phase II study of recombinant human interferon gamma (S-6810) in renal cell carcinoma. Urological Cooperative Study Group of Recombinant Human Interferon Gamma (S-6810)].

    Machida, T; Koiso, K; Takaku, F; Ogawa, M


    A phase II study of recombinant human interferon gamma (rHuIFN-gamma) administered intravenously and intramuscularly was carried out in 84 patients with advanced renal cell carcinoma with the cooperation of 18 institutions throughout Japan. The eligibility of the patients and evaluation of the responses were undertaken according to the general criteria proposed by Drs. Koyama and Saito. Out of 84 cases entered in this phase II study, 62 patients were evaluable for antitumor effects. In the case of continuous administration of 8-12 X 10(6) U/m2/day interferon for 4 weeks, 32 patients were evaluable. The response rate was 6.3%. In the case of intermittent therapy of 40 X 10(6) U/m2/day interferon for 8 weeks, six out of 30 patients (20%) were evaluable as responders. Among them, one patient showed a complete response, all patients tolerated this type of interferon well. Major adverse effects were fever (86.8%), anorexia (67.1%), fatigue (53.9%) and leukopenia (42.1%). No life-threatening toxicities were found. The results of this study showed that rHuIFN-gamma had antitumor activity against renal cell carcinoma. PMID:3101607

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

    Magee, D M; Cox, R A


    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 ...

  6. Fingolimod versus interferon beta/glatiramer acetate after natalizumab suspension in multiple sclerosis.

    Iaffaldano, Pietro; Lucisano, Giuseppe; Pozzilli, Carlo; Brescia Morra, Vincenzo; Ghezzi, Angelo; Millefiorini, Enrico; Patti, Francesco; Lugaresi, Alessandra; Zimatore, Giovanni Bosco; Marrosu, Maria Giovanna; Amato, Maria Pia; Bertolotto, Antonio; Bergamaschi, Roberto; Granella, Franco; Coniglio, Gabriella; Tedeschi, Gioacchino; Sola, Patrizia; Lus, Giacomo; Ferrò, Maria Teresa; Iuliano, Gerardo; Corea, Francesco; Protti, Alessandra; Cavalla, Paola; Guareschi, Angelica; Rodegher, Mariaemma; Paolicelli, Damiano; Tortorella, Carla; Lepore, Vito; Prosperini, Luca; Saccà, Francesco; Baroncini, Damiano; Comi, Giancarlo; Trojano, Maria


    The comparative effectiveness of fingolimod versus interferon beta/glatiramer acetate was assessed in a multicentre, observational, prospectively acquired cohort study including 613 patients with relapsing multiple sclerosis discontinuing natalizumab in the Italian iMedWeb registry. First, after natalizumab suspension, the relapse risk during the untreated wash-out period and during the course of switch therapies was estimated through Poisson regression analyses in separated models. During the wash-out period an increased risk of relapses was found in patients with a higher number of relapses before natalizumab treatment (incidence rate ratio = 1.31, P = 0.0014) and in patients discontinuing natalizumab due to lack of efficacy (incidence rate ratio = 2.33, P = 0.0288), patient's choice (incidence rate ratio = 2.18, P = 0.0064) and adverse events (incidence rate ratio = 2.09, P = 0.0084). The strongest independent factors influencing the relapse risk after the start of switch therapies were a wash-out duration longer than 3 months (incidence rate ratio = 1.78, P < 0.0001), the number of relapses experienced during and before natalizumab treatment (incidence rate ratio = 1.61, P < 0.0001; incidence rate ratio = 1.13, P = 0.0118, respectively) and the presence of comorbidities (incidence rate ratio = 1.4, P = 0.0097). Switching to fingolimod was associated with a 64% reduction of the adjusted-risk for relapse in comparison with switching to interferon beta/glatiramer acetate (incidence rate ratio = 0.36, P < 0.0001). Secondly, patients who switched to fingolimod or to interferon beta/glatiramer acetate were propensity score-matched on a 1-to-1 basis at the switching date. In the propensity score-matched sample a Poisson model showed a significant lower incidence of relapses in patients treated with fingolimod in comparison with those treated with interferon beta/glatiramer acetate (incidence rate ratio = 0.52, P = 0.0003) during a 12-month follow-up. The cumulative

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

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


    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...

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

    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: [Neurology Department, University of Vermont College of Medicine, Burlington, VT (United States)


    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.

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

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


    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...

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

    Nansen, A; Christensen, Jan Pravsgaard; Röpke, C; Marker, O; Scheynius, A; Thomsen, Allan Randrup


    Generally, interferon-gamma (IFN-gamma) is considered a critical regulator of T cell mediated inflammation. For this reason, we investigated the pathogenesis of lymphocytic choriomeningitis in mice with a targeted defect of the gene encoding this cytokine. Our results revealed that IFN-gamma is...... inflammatory exudate disclosed that leucocyte recruitment was unimpaired in the absence of IFN-gamma as was the upregulation of ICAM-1 and VCAM-1 on endothelium at the inflammatory site. However, local macrophage activation (production of tumor necrosis-alpha and NO) was significantly impaired. Notably, 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...

  11. Novel Beta-Gamma Coincidence Measurements Using Phoswich Detectors

    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

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

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


    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

  13. A system for simultaneous beta and gamma spectroscopy

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


    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.

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

    Krakauer, Martin


    -lymphocytes produce proinflammatory cytokines, which induce pathogenic effector cells. Recently, another Th subset relevant to MS has been identified. This is termed Th17 and is partly induced by IL-23. T-cells respond to chemotactic cytokines, termed chemokines, in order to migrate towards sites of...... during IFN-beta therapy. In conclusion, we have identified a subset of memory CD4+ lymphocytes which may be of special interest in the search for a surrogate marker of disease severity and, possibly, the risk of imminent clinical relapse in MS. Similarly, CXCL10, IL-10 and IL-23 mRNA expression should be...

  15. Enhanced production of murine interferon gamma by T cells generated in response to bacterial infection


    Spleen cell cultures derived from animals infected 6 d earlier with Listeria monocytogenes produced 10-20-fold more murine interferon gamma (MuIFN gamma) than spleen cells from nonimmune mice in response to stimulation with T cell mitogens. A striking temporal association was found between the enhanced synthesis of MuIFN gamma and the development of anti-Listeria immunity in that both the potential for increased MuIFN gamma production and the generation of Listeria-protective T cells develope...

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

    Xiong Zhang; Lu Si; Yu Li; Can Mi


    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.

  17. Interferon-gamma release-assay ved mistanke om aktiv tuberkulose?

    Browatzki, Andrea; Meyer, Christian


    INTRODUCTION: The purpose of this retrospective study was to outline the practical use and clinical value of the immunodiagnostic interferon-gamma release assay (IGRA) on suspicion of active Mycobacterium tuberculosis (TB) infection. MATERIAL AND METHODS: A retrospective study of all patients (n=91...

  18. Bovine Tuberculosis: Effect of the Tuberculin Skin Test on In vitro Interferon gamma Responses

    Bovine tuberculosis (bTB) is a disease of zoonotic and economic importance. In many countries, control is based on test and slaughter policies and/or abattoir surveillance. For testing, cell mediated immune- (CMI-) based assays (i.e., Tuberculin skin test (TST) supplemented by the interferon gamma (...

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

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


    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


    Neospora caninum is an obligate intracellular protozoan parasite, causing bovine abortion worldwide. Our recent research showed that N. caninum tachyzoite lysate elicits production of the T cell cytokine interferon-gamma (IFN-g) by both bovine and murine T cells, which may be critical to host protec...

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

    Hua ZHANG; Hai Ming WEI; Wen Rui JIN


    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.

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

    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...

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

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


    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...

  4. Competition of $\\beta$-delayed protons and $\\beta$-delayed $\\gamma$ rays in $^{56}$Zn and the exotic $\\beta$-delayed $\\gamma$-proton decay

    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; 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


    Remarkable results have been published recently on the $\\beta$ decay of $^{56}$Zn. In particular, the rare and exotic $\\beta$-delayed $\\gamma$-proton emission has been detected for the first time in the $fp$ shell. Here we focus the discussion on this exotic decay mode and on the observed competition between $\\beta$-delayed protons and $\\beta$-delayed $\\gamma$ rays from the Isobaric Analogue State.

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

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


    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.

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

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


    . Here we analyze the role of IFN-gamma during EAE by using both IFN-gamma receptor-knockout (IFN-gamma R(-/-)) and wild-type mice, both strains immunized with peptide 40-55 from rat myelin oligodendrocyte glycoprotein. The levels of oxidative stress were determined through the analysis of...... stress, MT-I+II, and apoptotic cell death by EAE were significantly increased in all mice, though more so in IFN-gamma R(-/-) mice compared with wild-type mice. These data support the notion that IFN-gamma has a protective role against EAE....... disease eliciting secretion of proinflammatory cytokines like IFN-gamma or TNF-alpha, and it has been suggested that cytokine-induced oxidative stress could have a role in EAE neuropathology. However, the individual roles of these and other cytokines in the pathogenesis of the disease are still uncertain...

  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



    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...

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

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


    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

  9. Skin Necrosis Following a Recombinant Interferon-beta-1b Injection

    Chih-Hsun Yang


    Full Text Available Recombinant interferon beta-1b (INF-β-1b has been proven to be an effective means oftreating relapsing-remitting multiple sclerosis (MS. Adverse reactions to interferon therapyhave been well documented. The most common side effects are transient influenza-likesymptoms, including fever, fatigue, nausea, and myalgia. Cutaneous necrosis has occasionallybeen reported, mostly involving small and limited lesions. This article describes an MSpatient who developed multiple large, deep cutaneous ulcers on INF-β-1b injection sites,which subsequently required surgical treatment. Vessel thrombosis in the subcutaneous fattylayer and the clinical appearance of livedoid erythema beside the ulcers indicated that INF-β-1b may have caused skin necrosis through its vascular effects.

  10. Ultrastructural effects of recombinant gamma-interferon on cultured human keratinocytes.

    Nickoloff, B J; Mahrle, G; Morhenn, V


    To extend our initial observations that recombinant gamma-interferon (r gamma IFN) influences the growth and differentiation of normal cultured human keratinocytes, we studied the electron microscopic changes induced by r gamma IFN. Treatment of cultured human keratinocytes with 10(3) units/ml (7.1 nM) of r gamma IFN produced a shift toward an increasing percentage of attached cells that had a mature-type, differentiated appearance rather than a basal type of proliferating cell, as observed in control, untreated cultures. This report extends the number of cell types that can be influenced by r gamma IFN at the ultrastructural level and supports the notion that r gamma IFN can influence both growth and maturation of normal cultured human keratinocytes. PMID:2421470

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

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


    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.

  12. The value of adenosine deaminase, interferon-gamma, and interferon-gamma induced protein of 10kD in the diagnosis of tuberculous pleuritis

    Ya-kun DONG; Li, Ai-zhen; Li-heng ZHENG; Yue-peng CHI; Wang, Yu-Hong; Qiu-mei WANG; Zhu, Gui-Yun; Lan-pin XIE


    Objective To explore the value of adenosine deaminase (ADA) activity, interferon-gamma (IFN-γ) and IFN-γ induced protein of 10kD (IP-10) levels in pleural effusion for the diagnosis of tuberculous pleuritis. Methods ADA activity, IFN-γ and IP-10 levels in pleural effusion were determined in sixty-three patients with tuberculous pleuritis and 50 patients with malignant pleural effusion. Results The mean levels of ADA, IFN-γ and IP-10 in the tuberculous pleural effusion were significantly highe...

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

    Zecca C; Yawalkar N; Gobbi C


    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...

  14. Early detection of neutralizing antibodies to interferon-beta in multiple sclerosis patients

    Hegen, H; Millonig, A; Bertolotto, A;


    BACKGROUND: Neutralizing antibodies (NAb) affect efficacy of interferon-beta (IFN-b) treatment in multiple sclerosis (MS) patients. NAbs evolve in up to 44% of treated patients, usually between 6-18 months on therapy. OBJECTIVES: To investigate whether early binding antibody (BAb) titers or...... after 3, 12 and 24 months on that therapy; for determination of NAbs, BAbs, gene expression of MxA and protein concentrations of MMP-9, TIMP-1, sTRAIL, CXCL-10 and CCL-2. RESULTS: We found that 22 of 164 (13.4%) patients developed NAbs during a median time of 23.8 months on IFN-b treatment. Of these...

  15. Interferon

    De Somer,P


    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.

  16. 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.

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


    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.

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

    Jensen, Jakob; Krakauer, Martin; Sellebjerg, Finn


    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...... inconsistent. We found decreases in CD4 and CD8 T cell expression of the CD49d/VLA-4 molecule, increases in plasma concentrations of soluble vascular cell adhesion molecule (sVCAM-1), and increases in plasma concentrations of tumor necrosis factor and interleukin (IL)-12 p40 chain in patients with MS who were...

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

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


    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....

  19. Interferon-gamma Immunotherapy in a Patient With Refractory Disseminated Candidiasis.

    Buddingh, Emilie P; Leentjens, Jenneke; van der Lugt, Jasper; Dik, Willem A; Gresnigt, Mark S; Netea, Mihai G; Pickkers, Peter; Driessen, Gertjan J


    Despite advances in supportive care and novel antifungal agents, mortality caused by invasive Candida infection is high. A 3-year-old boy with disseminated Candida dubliniensis infection during induction chemotherapy for acute lymphoblastic leukemia deteriorated despite resolution of neutropenia and appropriate antifungal treatment. Monocyte human leukocyte antigen-DR expression was extremely low, suggesting immunoparalysis. Adjuvant immunotherapy with interferon-gamma restored the immune response, which was accompanied by clinical and radiographic recovery. PMID:26379166

  20. Statistical modelling of masked gene regulatory pathway changes across microarray studies of interferon gamma activated macrophages

    Forster, Thorsten


    Interferon gamma (IFN-γ) regulation of macrophages plays an essential role in innate immunity and pathogenicity of viral infections by directing large and small genome-wide changes in the transcriptional program of macrophages. Smaller changes at the transcriptional level are difficult to detect but can have profound biological effects, motivating the hypothesis of this thesis that responses of macrophages to immune activation by IFN-γ include small quantitative changes that are m...

  1. Killed Candida albicans Yeasts and Hyphae Inhibit Gamma Interferon Release by Murine Natural Killer Cells

    Murciano, Celia; Villamón, Eva; O'Connor, José-Enrique; Gozalbo, Daniel; Gil, M. Luisa


    Killed yeasts and hyphae of Candida albicans inhibit gamma interferon secretion by highly purified murine NK cells in response to the Toll-like receptor ligands lipopolysaccharide and zymosan. This effect, which is also observed in the presence of NK-activating cytokines (interleukin-2 [IL-2], IL-12, and IL-15), may represent a novel mechanism of immune evasion that contributes to the virulence of C. albicans.

  2. Killed Candida albicans yeasts and hyphae inhibit gamma interferon release by murine natural killer cells.

    Murciano, Celia; Villamón, Eva; O'Connor, José-Enrique; Gozalbo, Daniel; Gil, M Luisa


    Killed yeasts and hyphae of Candida albicans inhibit gamma interferon secretion by highly purified murine NK cells in response to the Toll-like receptor ligands lipopolysaccharide and zymosan. This effect, which is also observed in the presence of NK-activating cytokines (interleukin-2 [IL-2], IL-12, and IL-15), may represent a novel mechanism of immune evasion that contributes to the virulence of C. albicans. PMID:16428793

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

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


    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

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


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

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


    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 ...

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



    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



    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.

  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



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

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


    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

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

    Sandro Pierdomenico


    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

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

    Jennifer eRitchie


    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

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

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


    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

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

    Carbonell Dalia


    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.

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

    Enevold, Christian; Oturai, Annette Bang; Sørensen, Per Soelberg; Ryder, Lars P.; Koch-Henriksen, Nils; Bendtzen, Klaus


    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....

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

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


    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...

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

    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 ...

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

    Éric Toussirot


    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.

  18. Induction of HLA-DR antigen on human squamous carcinoma by recombinant interferon gamma.

    Koch, W M; Dugan, E; Diaz, L A; Richtsmeier, W J


    The antigen recognition system which plays the major role in immunologic attraction mechanisms, including graft rejection, is the class II major histocompatibility complex containing the HLA-DR locus. Few types of cells constitutively express this antigen, as it is a potent immunological activating signal usually confined to antigen processing cells, activated lymphocytes, and endothelium. Using indirect immunofluorescence, we have observed induction of the HLA-DR glycoprotein in selected head and neck squamous cell carcinoma tissue cultures treated with recombinant interferon gamma. This occurs in concert with growth arrest and morphological changes after rHuIFN-gamma treatment. This report describes the induction of a surface antigen that may have profound prognostic significance. Understanding the kinetics of HLA-DR induction will aid in the design and assessment of adoptive immunotherapy with rHuIFN-gamma. PMID:3129628

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

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

    A total of 315 cattle were tested for infection with Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) at three consecutive samplings, using the interferon-gamma (IFN-gamma) test on whole blood and bacteriological culture of faecal samples. Of 205 cattle from 10 infected herds 99 ...

  20. Evaluation of a Second Generation BOVIGAM Interferon Gamma (IFN-gamma) Assay with Alternative Antigens for Stimulation of Whole Blood Cultures

    BOVIGAM®, a rapid laboratory assay, measures gamma interferon (IFN-gamma) production in whole blood samples after induction of a cell-mediated immune response (CMI) with M. bovis antigens. The test is widely used in the field and its excellent performance in TB eradication programs in many countries...

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

    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.

  2. Influence of apolipoprotein E plasma levels and tobacco smoking on the induction of neutralising antibodies to interferon-beta

    Sena, Armando; Bendtzen, Klaus; Cascais, Maria J;


    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....

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

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


    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...

  4. Population tailored modification of tuberculosis specific interferon-gamma release assay

    Horvati, Kata; Bősze, Szilvia; Gideon, Hannah P.; Bacsa, Bernadett; Szabó, Tamás G.; Goliath, Rene; Rangaka, Molebogeng X.; Hudecz, Ferenc; Wilkinson, Robert J.; Wilkinson, Katalin A.


    Summary Objectives Blood-based Interferon-Gamma Release Assays (IGRA) identify Mycobacterium tuberculosis (MTB) sensitisation with increased specificity, but sensitivity remains impaired in human immunodeficiency virus (HIV) infected persons. The QuantiFERON-TB Gold In-Tube test contains peptide 38–55 of Rv2654c, based on data indicating differential recognition between tuberculosis patients and BCG vaccinated controls in Europe. We aimed to fine map the T cell response to Rv2654c with the view of improving sensitivity. Methods Interferon-gamma ELISpot assay was used in HIV uninfected persons with latent and active tuberculosis to map peptide epitopes of Rv2654c. A modified IGRA was tested in two further groups of 55 HIV uninfected and 44 HIV infected persons, recruited in South Africa. Results The most prominently recognised peptide was between amino acids 51–65. Using p51-65 to boost the QuantiFERON-TB Gold In-Tube assay, the quantitative performance of the modified IGRA increased from 1.83 IU/ml (IQR 0.30–7.35) to 2.83 (IQR 0.28–12.2; p = 0.002) in the HIV uninfected group. In the HIV infected cohort the percentage of positive responders increased from 57% to 64% but only after 3 months of ART (p = ns). Conclusions Our data shows the potential to population tailor detection of MTB sensitization using specific synthetic peptides and interferon-gamma release in vitro. PMID:26632326

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

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

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

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


    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...

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

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


    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...

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

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


    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

  9. Interpretation of the Gamma Interferon Test for Diagnosis of Subclinical Paratuberculosis in Cattle

    Jungersen, G; Huda, A; Hansen, J. J.; Lind, P.


    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-γ) 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...

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

    Renno, T; Taupin, V; Bourbonnière, L;


    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...... of transgenic mice. MHC I immunostaining and iNOS mRNA were upregulated in their CNS, but such transgenic mice showed no spontaneous CNS inflammation or demyelination, and the incidence, severity, and histopathology of experimental autoimmune encephalomyelitis (EAE) were similar to nontransgenic...

  11. Sensitive detection of interferon-gamma with engineered proteins and surface plasmon resonance biosensor

    Šípová, Hana; Ševců, Veronika; Kuchař, Milan; Ahmad, Jawid; Mikulecký, Pavel; Šebo, Peter; Malý, Petr; Homola, Jiří

    Vol. 25. Amsterdam : Elsevier, 2011 - (Tsamis, C.; Kaltsas, G.), s. 940-943 ISBN 978-1-62748-581-4. ISSN 1877-7058. [25th Eurosensors Conference. Athens (GR), 04.09.2011-07.09.2011] R&D Projects: GA AV ČR KAN200670701; GA AV ČR KAN200520702; GA MŠk OC09058 Institutional research plan: CEZ:AV0Z20670512; CEZ:AV0Z50520701; CEZ:AV0Z50200510 Keywords : Surface plasmon resonance * Biosensor * Interferon gamma Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering; EI - Biotechnology ; Bionics (BTO-N); CE - Biochemistry (MBU-M)

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


    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...

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

    Schelensky, Lilien


    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 ...

  14. [Treatment of advanced renal cell carcinoma with a combination of interferon alpha and gamma].

    Naito, S; Yasumasu, T; Kumazawa, J; Hiratsuka, Y; Sakamoto, K; Iguchi, A; Masaki, Z; Hasui, Y; Osada, Y; Kurozumi, T


    A total of 29 patients with advanced renal cell carcinoma entered a pilot study of combination therapy with interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma). IFN-alpha (HLBI: 3 x 10(6) IU, BALL 1:5 x 10(6) IU, IFN-alpha-2a: 9 x 10(6) IU or IFN-alpha-2b: 6 x 10(6) IU) was given intramuscularly every day and IFN-gamma (IFN-gamma-1a: 3 x 10(6) JRU) was given intravenously by drip infusion 3 times a week (every 2-3 days). The treatment was continued for 3 months as the induction therapy, and then the tumor response was evaluated. Of the 22 evaluable patients, 4 achieved a partial response (PR), 10 showed no change (NC), and in 8 the disease had progressed (PD) during the therapy. Thus, the overall response rate was 18.2% [95% confidence interval (CI) 2.1-34.3%]. A favorable response tended to be obtained in patients with good performance status or small pulmonary metastases, or in those who had no prior therapy with IFN-alpha, who received this treatment immediately subsequent to radical nephrectomy, or who received IFN-gamma as much as possible according to this regimen. Toxicity was evaluated in 28 patients: fever, general fatigue, anorexia, leukocytopenia and impaired liver function were frequently noted, and 3 patients were withdrawn from the study because of such adverse effects. In patients who had a PR or NC, the same dosage of IFN-alpha was continued to be given intramuscularly 2-3 times a week (every 2-4 days) as the maintenance therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7474618

  15. Expression of Interferon Gamma by a Recombinant Rabies Virus Strongly Attenuates the Pathogenicity of the Virus via Induction of Type I Interferon

    Barkhouse, Darryll A.; Garcia, Samantha A.; Bongiorno, Emily K.; Lebrun, Aurore; Faber, Milosz; Hooper, D. Craig


    Previous animal model experiments have shown a correlation between interferon gamma (IFN-γ) expression and both survival from infection with attenuated rabies virus (RABV) and reduction of neurological sequelae. Therefore, we hypothesized that rapid production of murine IFN-γ by the rabies virus itself would induce a more robust antiviral response than would occur naturally in mice. To test this hypothesis, we used reverse engineering to clone the mouse IFN-γ gene into a pathogenic rabies vir...

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

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


    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...

  17. Testing for latent tuberculosis infection using interferon gamma release assays in commercial sex workers at an outreach clinic in Birmingham.

    Daly, R; Khatib, N; Larkins, A; Dedicoat, M


    This report demonstrates that using interferon gamma release assays to screen for latent tuberculosis infection in female commercial sex workers in an outreach sexual health clinic is feasible and acceptable. Routine interferon gamma release assay use successfully identified high numbers of latent tuberculosis infection. Innovative approaches to treatment and follow up were required to improve treatment adherence in this group. Direct observation of therapy within the sexual health clinic was also feasible. Successful follow up was dependent on the support of outreach workers, interpreters and tuberculosis nurses. PMID:26589629

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

    O'Connell, J


    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.

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

    Slobodan M Jankovic


    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


    Graça Maria de Castro Viana


    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.

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

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

  2. Interferon gamma regulates accumulation of the proteasome activator PA28 and immunoproteasomes at nuclear PML bodies.

    Fabunmi, R P; Wigley, W C; Thomas, P J; DeMartino, G N


    PA28 is an interferon (gamma) (IFN(gamma)) inducible proteasome activator required for presentation of certain major histocompatibility (MHC) class I antigens. Under basal conditions in HeLa and Hep2 cells, a portion of nuclear PA28 is concentrated at promyelocytic leukemia oncoprotein (PML)-containing bodies also commonly known as PODs or ND10. IFN(gamma) treatment greatly increased the number and size of the PA28- and PML-containing bodies, and the effect was further enhanced in serum-deprived cells. PML bodies are disrupted in response to certain viral infections and in diseases such as acute promyelocytic leukemia (APL). Like PML, PA28 was delocalized from PML bodies by expression of the cytomegalovirus protein, IE1, and in NB4 cells, an APL model line. Moreover, retinoic acid treatment, which causes remission of APL in patients and reformation of PML-containing bodies in NB4 cells, relocalized PA28 to this site. In contrast, the proteasome, the functional target of PA28, was not detected at PML bodies under basal conditions in HeLa and Hep2 cells, but IFN(gamma) promoted accumulation of 'immunoproteasomes' at this site. These results establish PA28 as a novel component of nuclear PML bodies, and suggest that PA28 may assemble or activate immunoproteasomes at this site as part of its role in proteasome-dependent MHC class I antigen presentation. PMID:11112687

  3. 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

    Elena Don


    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.

  4. 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.

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


    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

  5. UV cross-linking of distinct proteins to the PRDII domain of the interferon-beta promoter

    Xanthoudakis, S.; Hiscott, J. (Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec (Canada))


    The human interferon-beta gene (IFN-beta) is transcriptionally activated in a variety of cell types, mediated in part by a decameric element, designated the PRDII domain (-55 to -64) which is the target for the transcription factor NF-kappa B. In the present study, we have examined factor binding to the PRDII domain in three cell lines (HeLa, U937, Jurkat) following treatment with known inducers of IFN-beta transcription and NF-kappa B binding activity. UV cross-linking analysis has revealed that in all 3 cell types two inducible proteins of 58 kD and 69 kD and one constitutive protein of 48 kD bind to the PRDII domain. These experiments suggest that multiple proteins may interact with this element to regulate IFN-beta gene transcription.

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

    Afsaneh Shirani


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

  7. Gamma and beta intra-operative imaging probes

    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.)

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

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


    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...

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

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


    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)

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

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


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

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



    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

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

    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...

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

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


    leukemia inhibitory factor. The correlation between JAK2 tyrosyl phosphorylation and IRS-1 tyrosyl phosphorylation in response to GH, interferon-gamma, and leukemia inhibitory factor and in cells expressing different GHR mutants, provides evidence that IRS-1 may interact with JAK2 or an auxiliary molecule...

  14. Multicenter randomized, controlled study of intramuscular administration of interferon-beta for the treatment of chronic hepatitis C.

    Castro, A; Suárez, D; Inglada, L; Carballo, E; Domínguez, A; Diago, M; Such, J; Del Olmo, J A; Pérez-Mota, A; Pedreira, J; Quiroga, J A; Carreño, V


    The intramuscular administration of interferon-beta (IFN-beta) at a dosage of 6 million units three times per week for 6 months has been evaluated in 90 patients included in a multicenter, randomized, controlled trial for the treatment of chronic hepatitis C. Transaminase levels were significantly reduced in IFN-beta-treated patients (p = 0.015) and were significantly lower with respect to those of the untreated controls (p = 0.040 at 6 months). Four treated (8%) and one untreated (2.5%) patients had normal transaminase values after 6 months. At study end (12 months), three quarters of the IFN-beta-treated patients had sustained transaminase normalization, whereas the untreated case had relapsed. Hepatitis C viremia was cleared in 6 (12%) treated patients but in none of the untreated controls (p = 0.058). Side effects of IFN-beta were infrequent (a mild flu-like syndrome in anorexia in 8%, headaches and weight loss in 8%, and hair loss in 4%). Leukocyte and platelet counts decreased during IFN-beta treatment, but no dose modifications were necessary. Such decreases were not statistically significant when compared with the levels in the untreated controls. Intramuscular IFN-beta at the dosage used has little efficacy in the treatment of chronic hepatitis C. Because of IFN-beta tolerance, higher doses and alternate routes of injection might prove beneficial for the treatment of this disease. PMID:9041468

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

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


    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

  16. A preliminary Phase I trial of partially purified interferon-gamma in patients with cancer.

    Sherwin, S A; Foon, K A; Abrams, P G; Heyman, M R; Ochs, J J; Watson, T; Maluish, A; Oldham, R K


    Thirty-three patients were treated in an escalating single-dose trial of partially purified nonrecombinant interferon-gamma (IFN-gamma). The first seven patients received intramuscular injections of IFN-gamma in doses up to 20 X 10(6) units/m2. When it became clear that these patients had no detectable antiviral activity in their serum, subsequent patients were treated by the intravenous route of administration, generally with 2-h infusions. A total of 26 patients received the agent intravenously in single escalating doses ranging from 0.2 to 60 X 10(6) units/m2, on a twice-weekly schedule for 4-6 weeks. The most common toxicities encountered included fever, chills, fatigue, anorexia, and occasional nausea and vomiting. No myelosuppression or hepatic toxicity was observed. A maximum tolerated dose for single-dose intravenous administration was defined as 50 X 10(6) units/m2 on the basis of unacceptable fatigue and prolonged systolic hypotension. Antiviral activity was detected in the serum following doses greater than 2 X 10(6) units/m2 when the IFN-gamma was administered intravenously. No evidence of antitumor activity was seen in this Phase I trial, although the treatment regimen employed did not lead to high or prolonged levels of serum IFN activity in the majority of patients. An accurate assessment of the antitumor activity of this particular IFN-gamma preparation will require Phase II trials employing multiple-treatment regimens. PMID:6439828

  17. Interferon-Gamma Gene Polymorphism in Iranian Patients with Multiple Sclerosis

    Maryam Izad


    Full Text Available Interferon- gamma (IFN- γ is an important immune regulator and inflammatory cytokine which is implicated in the pathogenesis of multiple sclerosis (MS. A single nucleotide polymorphism, T to A, at position +874 in the first intron has previously been shown. This polymorphism is associated with IFN- γ production level. To study the effect of this polymorphism on susceptibility to multiple sclerosis, we screened genomic DNA samples from clinically definite MS patients and their unaffected first-degree relatives as controls, using sequence-specific primers (PCR-SSP. The results indicated that MS patients showed a lower TT (21.2% vs. 30.3% and higher AA (21.2% vs. 12.1% genotypes compared to controls, although there were statistically no differences in the IFN- γ genotype distribution between these two groups. Thus, our data indicate that there is no association between IFN- γ +874 polymorphism and MS susceptibility or severity of the disease.

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

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


    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...... individual animal cannot establish whether the animal is infected or predict the future progression of disease in this animal. The IFN-γ assay should thus be used on a group of animals to test the level of exposure to paratuberculosis bacteria the animals have experienced, and thereby assist in maintaining...... 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 of...

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

    Yunes Panahi


    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

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

    Andrés Maria Villa


    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.

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

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


    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......), resulting in a loss of bioactivity and therapeutic benefit. OBJECTIVE: The primary objective of this study is to investigate the in vivo biological response to interferon-alpha (IFN-α) in MS patients, who have developed neutralising antibodies (NAbs) against IFN-β. DESIGN/METHODS: The study was an open......-label phase II study in 10 patients with relapsing-remitting MS with persisting NAbs against IFN-β and absent in vivo mRNA MxA response. We used in vivo induction of MX1 mRNA and other IFN-inducible genes as measure of the biological response. The primary endpoint was the in vivo mRNA MX1 response after an...

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

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


    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

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


    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...

  4. Phase I evaluation of recombinant tumor necrosis factor given in combination with recombinant interferon-gamma.

    Smith, J W; Urba, W J; Clark, J W; Longo, D L; Farrell, M; Creekmore, S P; Conlon, K C; Jaffe, H; Steis, R G


    In light of in vitro and preclinical animal model data suggesting potential additive or synergistic antitumor effects from the combined use of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), we conducted a phase I study employing escalating doses of each agent in 36 patients with solid tumors to determine the maximum tolerated dose (MTD). Patients were given an intramuscular (i.m.) injection of IFN-gamma, followed 5 min later by an i.m. injection of TNF-alpha, each agent in different sites, every other day for ten doses over 20 days. Patients received 10, 50, or 100 micrograms/m2 of each agent throughout the treatment course. No dose modifications were made. Patients suffering serious toxicity had therapy stopped and were considered to be off-study. All patients experienced fatigue, and 36% spent over half their time in bed on treatment days. Fever and chills were nearly universal. Mild to moderate elevations in serum transaminase levels were noted in 44% of patients, and 44% developed transient microscopic hematuria. Although 81% of patients had anorexia, only 17% of patients lost more than 3 kg of body wt during the 3 weeks of therapy. Because two of three patients receiving 100 micrograms/m2 of both agents developed serious toxicity (one fever greater than 105 degrees F, one thrombocytopenia 43,000/mm3), the MTD was established to be 100 micrograms/m2 of IFN-gamma plus 50 micrograms/m2 of TNF-alpha. The use of aspirin did not significantly alter the toxic effects of the agents. One patient with melanoma had a mixed response and one patient with mesothelioma transiently cleared his ascites of malignant cells. PMID:1790143

  5. Interferon-gamma deficiency modifies the effects of a chronic stressor in mice: Implications for psychological pathology.

    Litteljohn, Darcy; Cummings, Amie; Brennan, Ashley; Gill, Anudip; Chunduri, Siri; Anisman, Hymie; Hayley, Shawn


    Pro-inflammatory cytokines promote behavioral and neurochemical variations similar to those evident following stressor exposure, and have been implicated in promoting depressive illness. Indeed, immunotherapeutic application of the cytokine, interferon-alpha, promoted depressive illness in cancer and hepatitis C patients. We assessed the possibility that another interferon cytokine family member, interferon-gamma (IFN-gamma), might contribute to the behavioral and biochemical alterations provoked by a chronic stressor regimen that has been used to model neuropsychiatric pathology in rodents. As predicted, IFN-gamma-deficient mice displayed basal differences in behavior (e.g., reduced open field exploration) and altered neurochemical activity (e.g., increased noradrenergic and serotonergic activity within the central amygdala), relative to their wild-type counterparts. Moreover, stressor-induced elevations of corticosterone and the pro-inflammatory cytokine, tumor necrosis factor-alpha, were attenuated in IFN-gamma-deficient mice. Similarly, the IFN-gamma null mice were refractory to the chronic stressor-induced alterations of dopamine metabolism (within the prefrontal cortex, paraventricular nucleus of the hypothalamus and central amygdala) evident in wild-type mice. Yet, the chronic stressor provoked signs of anxiety (e.g., reduced open field exploration) and depression-like behavior (e.g., increased forced swim immobility, reduced consumption of a palatable solution) among both wild-type and IFN-gamma knockout mice alike, suggesting a dissociation of behavioral functioning from the stressor-induced alterations of immunological, hormonal and dopaminergic activity. Together, these data suggest a complex neurobehavioral phenotype, wherein IFN-gamma deletion engenders a state of heightened basal emotionality coupled with increased monoaminergic activity in the amygdala. At the same time, however, IFN-gamma deficiency appears to blunt some of the neurochemical

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

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

  7. Beta-gamma contaminated solid waste incinerator facility

    This technical data summary outlines a reference process to provide a 2-stage, 400 lb/hour incinerator to reduce the storage volume of combustible process waste contaminated with low-level beta-gamma emitters in response to DOE Manual 0511. This waste, amounting to more than 200,000 ft3 per year, is presently buried in trenches in the burial ground. The anticipated storage volume reduction from incineration will be a factor of 20. The incinerator will also dispose of 150,000 gallons of degraded solvent from the chemical separations areas and 5000 gallons per year of miscellaneous nonradioactive solvents which are presently being drummed for storage

  8. Exoemissive properties of graphite. [Gamma, beta, X, aud UV, radiation

    Lapraz, D.; Iacconi, P.; Keller, P. (Nice Univ., 06 (France). Lab. de Physique Experimentale); Barthe, J. (CEA Centre d' Etudes Nucleaires de Fontenay-aux-Roses, 92 (France). Dept. de Protection)


    The exoemission of the commonly used graphite is far from negligible when the doses are higher than in the case of dosimetric applications. Some exoemissive experimental results for graphite, between room temperature and 710/sup 0/C, are given after various irradiations: UV (Hg - 253.7 nm), ..beta.. (/sup 90/Sr), X (W-target, 45 kV) or ..gamma.. (/sup 137/Cs). Mainly, six TSEE peaks located near 90, 160, 220, 300, 475 and 570/sup 0/C are observed. The origin of graphite exoemission is probably due to adsorption effects.

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

    Mumpower, Matthew; Moller, Peter


    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.

  10. Priming affects the activity of a specific region of the promoter of the human beta interferon gene.

    Dron, M; Lacasa, M; Tovey, M G


    Treatment of Daudi or HeLa cells with human interferon (IFN) alpha 8 before induction with either poly(I)-poly(C) or Sendai virus resulted in an 8- to 100-fold increase in IFN production. The extent of priming in Daudi cells paralleled the increase in the intracellular content of IFN-beta mRNA. IFN-alpha mRNA remained undetectable in poly(I)-poly(C)-treated Daudi cells either before or after priming. An IFN-resistant clone of Daudi cells was found to produce 4- to 20-fold more IFN after primi...

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

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


    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...

  12. Association study in naturally infected helminth layers shows evidence for influence of interferon-gamma gene variants on Ascaridia galli worm burden

    Lühken Gesine; Gauly Matthias; Kaufmann Falko; Erhardt Georg


    Abstract Single nucleotide polymorphisms (SNPs) in the genes for interleukin-4, -13 and interferon-gamma, and 21 additional SNPs which previously had been significantly associated with immune traits in the chicken, were genotyped in white and brown layer hens and analyzed for their association with helminth burden following natural infections. A nucleotide substitution located upstream of the promoter of the interferon-gamma gene was significantly associated with the log transformed number of...

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

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

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

    Stegall, T; Krolick, K A


    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

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

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

  16. Neutralization of lymphokine-mediated antirickettsial activity of fibroblasts and macrophages with monoclonal antibody specific for murine interferon gamma.

    Jerrells, T R; Turco, J; Winkler, H H; Spitalny, G L


    Lymphokine-mediated inhibition of Rickettsia prowazekii multiplication in L929 fibroblasts was eliminated by treatment of the lymphokine with a monoclonal antibody specific for interferon-gamma. Soluble monoclonal antibody and antibody conjugated to Sepharose beads were equally effective. Macrophage activation to limit the multiplication of Rickettsia conorii was eliminated with antibody-conjugated beads; however, neutralization of the ability to activate macrophages with soluble antibody was...

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

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


    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...

  18. Interaction of Interferon Gamma-Induced Reactive Oxygen Species with Ceftazidime Leads to Synergistic Killing of Intracellular Burkholderia pseudomallei

    Mosovsky, Kara; Silva, Ediane; Troyer, Ryan; Propst-Graham, Katie; Dow, Steven


    Burkholderia pseudomallei, a facultative intracellular pathogen, causes severe infections and is inherently refractory to many antibiotics. Previous studies from our group have shown that interferon gamma (IFN-γ) interacts synergistically with the antibiotic ceftazidime to kill bacteria in infected macrophages. The present study aimed to identify the underlying mechanism of that interaction. We first showed that blocking reactive oxygen species (ROS) pathways reversed IFN-γ- and ceftazidime-m...

  19. Interferon-gamma coordinates CCL3-mediated neutrophil recruitment in vivo

    Foster Barbara


    Full Text Available Abstract Background We have shown previously that acute infection with the respiratory pathogen, pneumonia virus of mice (PVM, results in local production of the proinflammatory chemokine, CCL3, and that neutrophil recruitment in response to PVM infection is reduced dramatically in CCL3 -/- mice. Results In this work, we demonstrate that CCL3-mediated neutrophil recruitment is coordinated by interferon-gamma (IFNγ. Neutrophil recruitment in response to PVM infection was diminished five-fold in IFNγ receptor gene-deleted mice, although neutrophils from IFNγR -/- mice expressed transcripts for the CCL3 receptor, CCR1 and responded functionally to CCL3 ex vivo. Similarly, in the absence of PVM infection, CCL3 overexpression alone could not elicit neutrophil recruitment in the absence of IFNγ. Interestingly, although supplemental IFNγ restored neutrophil recruitment and resulted in a sustained weight loss among CCL3-overexpressing IFNγ -/- mice, CCL3-mediated neutrophil recruitment alone did not result in the pulmonary edema or respiratory failure characteristic of severe viral infection, suggesting that CCL3 and IFN-γ together are sufficient to promote neutrophil recruitment but not pathologic activation. Conclusion Our findings reveal a heretofore unrecognized hierarchical interaction between the IFNγ and CCL3, which demonstrate that IFNγ is crucial for CCL3-mediated neutrophil recruitment in vivo.

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

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


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

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

    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


    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

  2. A new role for interferon gamma in neural stem/precursor cell dysregulation

    Hartung Hans-Peter


    Full Text Available Abstract Background The identification of factors that compromise neurogenesis is aimed at improving stem cell-based approaches in the field of regenerative medicine. Interferon gamma (IFNγ is a main pro-inflammatory cytokine and up-regulated during several neurological diseases. IFNγ is generally thought to beneficially enhance neurogenesis from fetal or adult neural stem/precursor cells (NSPCs. Results We now provide direct evidence to the contrary that IFNγ induces a dysfunctional stage in a substantial portion of NSPC-derived progeny in vitro characterized by simultaneous expression of glial fibrillary acid protein (GFAP and neuronal markers, an abnormal gene expression and a functional phenotype neither typical for neurons nor for mature astrocytes. Dysfunctional development of NSPCs under the influence of IFNγ was finally demonstrated by applying the microelectrode array technology. IFNγ exposure of NSPCs during an initial 7-day proliferation period prevented the subsequent adequate differentiation and formation of functional neuronal networks. Conclusions Our results show that immunocytochemical analyses of NSPC-derived progeny are not necessarily indicating the correct cellular phenotype specifically under inflammatory conditions and that simultaneous expression of neuronal and glial markers rather point to cellular dysregulation. We hypothesize that inhibiting the impact of IFNγ on NSPCs during neurological diseases might contribute to effective neurogenesis and regeneration.

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

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

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

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


    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...

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

    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)


    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.

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

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


    treatment with IFN-beta. We use DNA microarrays to study gene expression in 10 multiple sclerosis (MS) patients who began de novo treatment with IFN-beta. After the first injection of IFN-beta, the expression of 74 out of 3428 genes changed at least two-fold and statistically significantly (after Bonferroni...

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

    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

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

    Georg Füllen


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

    Huda, A.; Jensen, H.E.


    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...

  10. 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

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


    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...

  11. 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

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


    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...

  12. Up-regulation of keratin 17 expression in human HaCaT keratinocytes by interferon-gamma.

    Bonnekoh, B; Huerkamp, C; Wevers, A; Geisel, J; Sebök, B; Bange, F C; Greenhalgh, D A; Böttger, E C; Krieg, T; Mahrle, G


    The immortalized human keratinocyte cell line HaCaT was used to assess the effect of interferon-gamma (IFN-gamma) on expression of keratin K17. Both IFN-gamma and K17 have been implicated in the pathophysiology of psoriasis. Western and quantitative enzyme-linked immunosorbent assay analyses demonstrated increasing induction of K17 protein by 48 h exposure to IFN-gamma at concentrations of 10, 50, and 250 U/ml. At 50 U/ml IFN-gamma, immunohistochemical analysis revealed numerous K17-positive foci, whereas in situ hybridization demonstrated K17 message in the majority of cells. In addition, at low (5 U/ml) concentrations of IFN-gamma, cell proliferation and protein synthesis decreased, as determined by 3H-thymidine labeling and 14C-amino acid uptake. These data suggest that aberrant K17 expression observed in psoriatic lesions may be a consequence of IFN-gamma overexpression, and that the HaCaT cell line may be a useful in vitro model system to elucidate the underlying mechanisms. PMID:7528246

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

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


    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

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

    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.

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

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


    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

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

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


    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...

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

    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


    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...

  18. Development of a three-layer phoswich alpha-beta-gamma imaging detector

    Yamamoto, Seiichi; Ishibashi, Hiroyuki


    For radiation monitoring at the sites of such nuclear power plant accidents as Fukushima Daiichi, radiation detectors are needed not only for gamma photons but also for alpha and beta particles because some nuclear fission products emit beta particles and gamma photons and some nuclear fuels contain plutonium that emits alpha particles. In some applications, imaging detectors are required to detect the distribution of plutonium particles that emit alpha particles and radiocesium in foods that emits beta particles and gamma photons. To solve these requirements, we developed an imaging detector that can measure the distribution of alpha and beta particles as well as gamma photons. The imaging detector consists of three-layer scintillators optically coupled to each other and to a position sensitive photomultiplier tube (PSPMT). The first layer, which is made of a thin plastic scintillator (decay time: ~5 ns), detects alpha particles. The second layer, which is made of a thin Gd2SiO5 (GSO) scintillator with 1.5 mol% Ce (decay time: 35 ns), detects beta particles. The third layer made of a thin GSO scintillator with 0.4 mol% Ce (decay time: 70 ns) detects gamma photons. Using pulse shape discrimination, the images of these layers can be separated. The position information is calculated by the Anger principle from 8×8 anode signals from the PSPMT. The images for the alpha and beta particles and the gamma photons are individually formed by the pulse shape discriminations for each layer. We detected alpha particle images in the first layer and beta particle images in the second layer. Gamma photon images were detected in the second and third layers. The spatial resolution for the alpha and beta particles was ~1.25 mm FWHM and less than 2 mm FWHM for the gamma photons. We conclude that our developed alpha-beta-gamma imaging detector is promising for imaging applications not only for the environmental monitoring of radionuclides but also for medical and molecular imaging.

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

    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


    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

  20. In vitro and in ovo expression of chicken gamma interferon by a defective RNA of avian coronavirus infectious bronchitis virus.

    Hackney, Karen; Cavanagh, Dave; Kaiser, Pete; Britton, Paul


    Coronavirus defective RNAs (D-RNAs) have been used for site-directed mutagenesis of coronavirus genomes and for expression of heterologous genes. D-RNA CD-61 derived from the avian coronavirus infectious bronchitis virus (IBV) was used as an RNA vector for the expression of chicken gamma interferon (chIFN-gamma). D-RNAs expressing chIFN-gamma were shown to be capable of rescue, replication, and packaging into virions in a helper virus-dependent system following electroporation of in vitro-derived T7 RNA transcripts into IBV-infected cells. Secreted chIFN-gamma, under the control of an IBV transcription-associated sequence derived from gene 5 of the Beaudette strain, was expressed from two different positions within CD-61 and shown to be biologically active. In addition, following infection of 10-day-old chicken embryos with IBV containing D-RNAs expressing chIFN-gamma, the allantoic fluid was shown to contain biologically active chIFN-gamma, demonstrating that IBV D-RNAs can express heterologous genes in vivo. PMID:12719562

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

    Dian HE


    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

  2. Canine PHA-stimulated adherent cell enhance interferon-gamma production and proliferation of autologous peripheral blood mononuclear cells.

    Ide, Kaori; Momoi, Yasuyuki; Iwasaki, Toshiroh


    Dendritic cells are specialized antigen-presenting cells with immuno-modulating functions that are attractive for clinical applications for cancer immunotherapy. This study examined immunostimulatory functions of phytohemagglutinin (PHA)-stimulated adherent cells (PHA-Ad cells) from peripheral blood mononuclear cells (PBMCs) in dogs. PHA-Ad cells enhanced interferon-gamma from autologous PBMC in vitro. PHA-Ad cells also stimulated antigen-independent proliferation of peripheral blood lymphocytes. These results suggest that PHA-Ad cells from PBMC possess a stimulatory function to evoke anti-tumour immunity and that they demonstrate potential for therapeutic applications in dogs. PMID:19379211

  3. In Vitro and In Ovo Expression of Chicken Gamma Interferon by a Defective RNA of Avian Coronavirus Infectious Bronchitis Virus

    Hackney, Karen; Cavanagh, Dave; Kaiser, Pete; Britton, Paul


    Coronavirus defective RNAs (D-RNAs) have been used for site-directed mutagenesis of coronavirus genomes and for expression of heterologous genes. D-RNA CD-61 derived from the avian coronavirus infectious bronchitis virus (IBV) was used as an RNA vector for the expression of chicken gamma interferon (chIFN-γ). D-RNAs expressing chIFN-γ were shown to be capable of rescue, replication, and packaging into virions in a helper virus-dependent system following electroporation of in vitro-derived T7 ...

  4. Valutazione della produzione di gamma interferone in bovini vaccinati con Brucella abortus ceppo RB51 mediante un test ELISA

    Manuela Tittarelli


    Full Text Available In questo lavoro sono presentati i risultati di un test ELISA messo a punto per rilevare la produzione di gamma interferone (g-interferone in bovini vaccinati con Brucella abortus ceppo RB51 (RB51. Come stimolo antigenico per il sangue intero è stata utilizzata una frazione proteica purificata derivante da RB51 (brucellina RB51. La prova è stata valutata nell’arco di 300 giorni in 10 manze vaccinate in età prepubere con 10×109 Unità Formanti Colonia di RB51 e in cinque manze di controllo, provenienti da allevamenti ufficialmente indenni da brucellosi bovina. I capi vaccinati hanno cominciato a fornire risultati positivi a partire dal 17° giorno post vaccinazione (p.v. fino al giorno 239 p.v. Tutti i capi vaccinati hanno fornito almeno una volta un risultato positivo (indice di stimolazione, IS, superiore a 2,5. Tuttavia, se si esclude il prelievo al giorno 20 p.v. (90% di animali vaccinati risultati positivi, la sensibilità del test oscilla tra il 20% e il 70%, con una media del 40%. IS superiore a 2,5 è stato rilevato anche in tre animali di controllo. Sulla scorta dei risultati ottenuti, si ritiene che il test del g-interferone non fornisce garanzie sufficienti per consigliarne l’impiego ai fini di riconoscere i bovini vaccinati con RB51, sia come prova individuale, sia come prova d’allevamento.

  5. An ELISA for the evaluation of gamma interferon production in cattle vaccinated with Brucella abortus strain RB51

    Manuela Tittarelli


    Full Text Available The results of an enzyme-linked immunosorbent assay (ELISA implemented for the detection of gamma interferon (g-interferon production in cattle vaccinated with Brucella abortus strain RB51 are presented. A purified protein fraction derived from RB51 (RB51 brucellin has been used as antigenic stimulus for whole blood. The test was evaluated for 300 days in ten heifers vaccinated at calfhood with 10 × 109 colony-forming units of RB51 and in five control heifers. All animals came from officially brucellosis-free herds. Vaccinated animals started to give positive results from day 17 post vaccination (pv until day 239 pv. All vaccinated animals gave a positive reaction at least once (with a stimulation index exceeding 2.5. Nevertheless, if sampling on day 20 pv is excluded (90% of vaccinated animals gave positive results, the sensitivity of the test varies from 20% to 70%, with a 40% average. A stimulation index over 2.5 was also recorded in three control animals. The results suggest that the g-interferon test is not suitable for the detection of cattle vaccinated with RB51, either at the individual or at the herd level.

  6. Persistent virus infection despite chronic cytotoxic T-lymphocyte activation in gamma interferon-deficient mice infected with lymphocytic choriomeningitis virus

    Bartholdy, C; Christensen, Jan Pravsgaard; Wodarz, D;


    The role of gamma interferon (IFN-gamma) in the permanent control of infection with a noncytopathic virus was studied by comparing immune responses in wild-type and IFN-gamma-deficient (IFN-gamma -/-) mice infected with a slowly invasive strain of lymphocytic choriomeningitis virus (LCMV Armstrong......). While wild-type mice rapidly cleared the infection, IFN-gamma -/- mice became chronically infected. Virus persistence in the latter mice did not reflect failure to generate cytotoxic T-lymphocyte (CTL) effectors, as an unimpaired primary CTL response was observed. Furthermore, while ex vivo CTL activity...

  7. Angular dependence of thermoluminescent dosemeters for gamma and beta radiation in nuclear medicine

    The gamma and beta radiation sources are widely used in Nuclear Medicine for diagnostic and therapeutic purposes. Workers of these services receive dose of whole body and end due to the activities of the therapeutic dose preparation and testing, administration radiopharmaceuticals and obtention of image. Hands receive higher doses than other parts of the body. Currently the individual monitoring for the gamma radiation is already well established; However, the determination of the dose due to beta radiation still faces some difficulties. In this work it was studied the angular dependence of thermoluminescent dosemeters detectors in beams of gamma and beta radiation. Detectors of CaSO4:Dy + Teflon produced at IPEN - the Brazilian Institute for Nuclear and Energy Researches - were used. The angular dependence was studied varying the angle between 0 and 180 deg. The results obtained proved to be suitable for use in individual monitoring of workers exposed to beta and gamma radiation

  8. Estimate of beta and gamma contamination in vegetable and animal biologic samples using GM detectors

    The paper presents the use of a large area Geiger-Mueller Detector (GMD) with aluminium window of 50 mm thickness (3,4 mg/cm2) in a measuring chain in order to estimate the beta and gamma contamination of biologic samples. The technical data for GMD are: - window area for gamma radiation: 300 cm2; - grid transmission: 80%; - operating voltage: 1100 - 1300 V; - minimum detectable beta energy: 125 keV; - dead time: 250 ms; - background (shielded with 100 mm Pb + 1 mm Cu): 6 pulses/s; - service life: 5 x 108 counts. Using this GMD together with a set of large area beta standard sources and a set of point gamma sources we could estimate beta and gamma contamination in the energy range 125 keV - 2.5 MeV for biologic samples. (authors)

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

    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.

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

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


    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

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

    Hossein Malekzadeh


    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.

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

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


    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

  13. Interferon-beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization.

    Lückoff, Anika; Caramoy, Albert; Scholz, Rebecca; Prinz, Marco; Kalinke, Ulrich; Langmann, Thomas


    Age-related macular degeneration (AMD) is a leading cause of vision loss among the elderly. AMD pathogenesis involves chronic activation of the innate immune system including complement factors and microglia/macrophage reactivity in the retina. Here, we show that lack of interferon-β signaling in the retina accelerates mononuclear phagocyte reactivity and promotes choroidal neovascularization (CNV) in the laser model of neovascular AMD Complete deletion of interferon-α/β receptor (Ifnar) using Ifnar1(-/-) mice significantly enhanced early microglia and macrophage activation in lesion areas. This triggered subsequent vascular leakage and CNV at later stages. Similar findings were obtained in laser-treated Cx3cr1(Cre) (ER):Ifnar1(fl/fl) animals that allowed the tamoxifen-induced conditional depletion of Ifnar in resident mononuclear phagocytes only. Conversely, systemic IFN-β therapy of laser-treated wild-type animals effectively attenuated microgliosis and macrophage responses in the early stage of disease and significantly reduced CNV size in the late phase. Our results reveal a protective role of Ifnar signaling in retinal immune homeostasis and highlight a potential use for IFN-β therapy in the eye to limit chronic inflammation and pathological angiogenesis in AMD. PMID:27137488

  14. Study of PIN diode based pocket dosimeter for gamma and beta radiation

    A pocket dosimeter, based on PN junction Si Semiconductor detector earlier was developed for the measurement of dose equivalent in the field of gamma and beta radiation. This dosemeter was insensitive to beta radiation which is primary requirement as a legal personal dosemeter from IEE standards. This dosemeter works on a high power 3V Li battery along with a micro power DC-DC converter to get 3.3V needed to power the circuit. It has a 6 digit LCD digital display along with battery low indication. It measures the dose range of 1- 99999 μSv. The photon energy dependence of the dosimeter from 60 keV to 1.2 MeV is ± 30% for gamma radiation and ± 40% for beta. Further work is in progress to bring beta response within acceptable limit and to display beta and gamma response separately as Hp (0.07) and Hp (10). (author)

  15. Gamma-interferon causes a selective induction of the lysosomal proteases, cathepsins B and L, in macrophages

    Lah, T. T.; Hawley, M.; Rock, K. L.; Goldberg, A. L.


    Previous studies have indicated that acid-optimal cysteine proteinase(s) in the endosomal-lysosomal compartments, cathepsins, play a critical role in the proteolytic processing of endocytosed proteins to generate the antigenic peptides presented to the immune system on major histocompatibility complex (MHC) class II molecules. The presentation of these peptides and the expression of MHC class II molecules by macrophages and lymphocytes are stimulated by gamma-interferon (gamma-IFN). We found that treatment of human U-937 monocytes with gamma-IFN increased the activities and the content of the two major lysosomal cysteine proteinases, cathepsins B and L. Assays of protease activity, enzyme-linked immunosorbant assays (ELISA) and immunoblotting showed that this cytokine increased the amount of cathepsin B 5-fold and cathepsin L 3-fold in the lysosomal fraction. By contrast, the aspartic proteinase, cathepsin D, in this fraction was not significantly altered by gamma-IFN treatment. An induction of cathepsins B and L was also observed in mouse macrophages, but not in HeLa cells. These results suggest coordinate regulation in monocytes of the expression of cathepsins B and L and MHC class II molecules. Presumably, this induction of cysteine proteases contributes to the enhancement of antigen presentation by gamma-IFN.

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

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


    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

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

    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

  18. Monocytic cells synthesize, adhere to, and migrate on laminin-8 (alpha 4 beta 1 gamma 1).

    Pedraza, C; Geberhiwot, T; Ingerpuu, S; Assefa, D; Wondimu, Z; Kortesmaa, J; Tryggvason, K; Virtanen, I; Patarroyo, M


    Laminins, a growing family of large heterotrimeric proteins with cell adhesive and signaling properties, are major components of vascular and other basement membranes. Expression, recognition, and use of laminin isoforms by leukocytes are poorly understood. In monoblastic THP-1 cells, transcripts for laminin gamma(1)-, beta(1)-, and alpha(4)-chains were detected by RT-PCR. Following immunoaffinity purification on a laminin beta(1) Ab-Sepharose column, laminin beta(1)- (220 kDa), gamma(1)- (200 kDa), and alpha(4)- (180/200 kDa) chains were detected by Western blotting in THP-1 cells and in two other monoblastic cell lines, U-937 and Mono Mac 6. After cell permeabilization, a mAb to laminin gamma(1)-chain reacted with practically all blood monocytes by immunofluorescence flow cytometry, and laminin-8 (alpha(4)beta(1)gamma(1)) could be isolated also from these cells. Monoblastic JOSK-I cells adhered constitutively to immobilized recombinant laminin-8, less than to laminin-10/11 (alpha(5)beta(1)gamma(1)/alpha(5)beta(2)gamma(1)) but to a higher level than to laminin-1 (alpha(1)beta(1)gamma(1)). Compared with the other laminin isoforms, adhesion to laminin-8 was preferentially mediated by alpha(6)beta(1) and beta(2) integrins. Laminin-8 and, to a lower extent, laminin-1 promoted spontaneous and chemokine-induced migration of blood monocytes, whereas laminin-10/11 was inhibitory. Altogether, the results indicate that leukocytes, as other cell types, are able to synthesize complete laminin molecules. Expression, recognition, and use of laminin-8 by leukocytes suggest a major role of this laminin isoform in leukocyte physiology. PMID:11067943

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

    Bhamidipati, Chandrasekhar; Ray, Koushik


    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.

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

    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)

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

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


    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

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

    Hedegaard, Chris J; Sellebjerg, Finn; Krakauer, Martin; Hesse, Dan; Bendtzen, Klaus; Nielsen, Claus H


    -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 <0.009) and MS severity score (p <0.05), but not with disease activity as determined by the number of gadolinium......-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 <0.002). However, an 11% decrease in IgM and a 33...

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

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


    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.

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

    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 3p-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. Calcineurin antagonists inhibit interferon-gamma production by downregulation of interleukin-18 in human mixed lymphocyte reactions.

    Kuinose M


    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.

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

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


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

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

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


    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

  8. 75 FR 4877 - In the Matter of Beta Gamma Nuclear Radiology; Confirmatory Order Modifying License (Effective...


    ... 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...

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

    Dissing-Olesen, Lasse; Thaysen-Andersen, Morten; Meldgaard, Michael; Højrup, Peter; Finsen, Bente


    counterpart, due to a protein stabilization/solubilization effect of the glycan. It is interesting to note that the terminating sialic acids were essential for these effects. Conclusively, the structure/bioactivity relationship of rhIFN-beta1a was determined in vivo, and it provided a novel insight into the...

  10. 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

    Kappos, Ludwig; Freedman, Mark S; Polman, Chris H;


    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...

  11. Inhibitory effect of interferon-gamma activated ovine umbilical vein endothelial cells on the intracellular replication of Toxoplasma gondii.

    Dimier, I H; Bout, D T


    Toxoplasma gondii is an obligate intracellular parasite that is a major cause of abortion and neonatal mortality in sheep. In congenital toxoplasmosis, T gondii first invades the umbilical vein endothelial cells and are then disseminated throughout the fetus. Treatment of ovine umbilical vein endothelial cells with bovine recombinant gamma-interferon (IFN-gamma) blocked the growth of T gondii. Growth of the parasite was measured by 3H-uracil incorporation 18 h after the onset of the infection and by microscopic enumeration of parallel cultures. This assay revealed that when the cells were pretreated with IFN-gamma in concentrations ranging from 0.15-1,250 U/mL, a high degree of inhibition of T gondii replication was observed with the effect being dose-dependent. Maximum activation was achieved by incubating with 625 U/mL IFN-gamma and no activity was present at 0.15 U/mL. This technique could be of relevance as a first line of defense against congenital ovine Toxoplasma infection. Inhibition of T gondii replication is due to a different mechanism from that existing in mouse macrophages and human fibroblasts. L-Arginine-dependent production of reactive nitrogen and oxygen intermediates was not responsible for the inhibition of T gondii replication. Supplements of five amino acids were able to overcome the inhibition partially but significantly. The mechanism of the inhibition remains to be elucidated. PMID:8822620

  12. Standardization of (18)F using the 4pi(beta+gamma) integral counting technique.

    Yamada, T; Kawada, Y; Sato, Y; Yunoki, A; Hino, Y


    Alpha 4pi(beta+gamma) integral counting technique using a 4pibeta-4pigamma detector configuration was adopted for the standardization of (18)F. In this technique, the beta-detector is composed of two thin plastic scintillators sandwiching the source, coupled with a slender photomultiplier tube. The beta-detector part with the source was inserted into a large well-type NaI(Tl) scintillation detector for gamma-ray detection, making a 4pibeta-4pigamma coincidence counting system. In this work, positron particles were detected with high efficiency in the beta-channel and annihilation quanta were also detected with high efficiency in the 4pigamma channel. The very small inefficiency of the 4pi(beta+gamma) integral counter for the beta-plus branch has been confirmed by EGS5 Monte Carlo simulation. The result using this technique agreed within the uncertainties with the result obtained by the conventional 4pibeta-gamma coincidence counting with the efficiency extrapolation technique using the same detector configuration and a conventional 4pibeta-gamma coincidence counter. PMID:18378155

  13. Impact of a switch to fingolimod versus staying on glatiramer acetate or beta interferons on patient- and physician-reported outcomes in relapsing multiple sclerosis: post hoc analyses of the EPOC trial

    Calkwood, Jonathan; Cree, Bruce; Crayton, Heidi; Kantor, Daniel; Steingo, Brian; Barbato, Luigi; Hashmonay, Ron; Agashivala, Neetu; McCague, Kevin; Tenenbaum, Nadia; Edwards, Keith


    Background The Evaluate Patient OutComes (EPOC) study assessed physician- and patient-reported outcomes in individuals with relapsing multiple sclerosis who switched directly from injectable disease-modifying therapy (iDMT; glatiramer acetate, intramuscular or subcutaneous interferon beta-1a, or interferon beta-1b) to once-daily, oral fingolimod. Post hoc analyses evaluated the impact of a switch to fingolimod versus staying on each of the four individual iDMTs. Methods Overall, 1053 patients...

  14. Effects of interferon gamma on Chlamydia trachomatis serovar A and L2 protein expression investigated by two-dimensional gel electrophoresis

    Shaw, A; Christiansen, Gunna; Birkelund, Svend


    Chlamydia trachomatis is an obligate intracellular bacterium causing human ocular and genital disease. The lymphokine interferon gamma (IFN-gamma) is an important immune effector exerting antimicrobial effects towards several intracellular parasites, the chlamydia included. IFN-gamma has been......]methionine and two-dimensional gel electrophoresis with immobilized pH gradients in order to investigate changes in the protein expression of C. trachomatis serovar A and L2 caused by treatment with IFN-gamma. In contrast to what was observed in C. trachomatis L2, our results showed that, in C. trachomatis A...

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

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


    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.

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

    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


    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...

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

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


    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

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

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


    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

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

    Hong Lei Weng; Wei Min Cai; Rong Hua Liu


    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

  20. 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.

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


    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...

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

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


    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...

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

    Bettina Trinschek


    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.

  3. Polymorphism discovery and association analyses of the interferon genes in type 1 diabetes

    Lam Alex C


    Full Text Available Abstract Background The aetiology of the autoimmune disease type 1 diabetes (T1D involves many genetic and environmental factors. Evidence suggests that innate immune responses, including the action of interferons, may also play a role in the initiation and/or pathogenic process of autoimmunity. In the present report, we have adopted a linkage disequilibrium (LD mapping approach to test for an association between T1D and three regions encompassing 13 interferon alpha (IFNA genes, interferon omega-1 (IFNW1, interferon beta-1 (IFNB1, interferon gamma (IFNG and the interferon consensus-sequence binding protein 1 (ICSBP1. Results We identified 238 variants, most, single nucleotide polymorphisms (SNPs, by sequencing IFNA, IFNB1, IFNW1 and ICSBP1, 98 of which where novel when compared to dbSNP build 124. We used polymorphisms identified in the SeattleSNP database for INFG. A set of tag SNPs was selected for each of the interferon and interferon-related genes to test for an association between T1D and this complex gene family. A total of 45 tag SNPs were selected and genotyped in a collection of 472 multiplex families. Conclusion We have developed informative sets of SNPs for the interferon and interferon related genes. No statistical evidence of a major association between T1D and any of the interferon and interferon related genes tested was found.

  4. Recombinant interferon gamma augments phagocyte superoxide production and X-chronic granulomatous disease gene expression in X-linked variant chronic granulomatous disease.

    Ezekowitz, R A; Orkin, S H; Newburger, P E


    We examined the potential of interferon gamma (IFN-gamma) to ameliorate the physiologic defect of chronic granulomatous disease (CGD) by studying its effects on CGD phagocyte superoxide generation, NADPH oxidase kinetics, cytochrome b559 content, and expression of X-CGD (the gene for the X-linked disease). Granulocytes and macrophages from three patients in two kindreds with "variant" X-linked CGD (i.e., with very low, but detectable, baseline superoxide-generating activity) responded to IFN-...

  5. Systemic infection of mice by wild-type but not Spv- Salmonella typhimurium is enhanced by neutralization of gamma interferon and tumor necrosis factor alpha.

    Gulig, P A; Doyle, T J; Clare-Salzler, M J; Maiese, R L; Matsui, H


    The spv genes of the virulence plasmid of Salmonella typhimurium and other nontyphoidal serovars of S. enterica are involved in systemic infection by increasing the replication rate of the bacteria in host tissues beyond the intestines. We considered the possibility that the Spv virulence function is to evade suppression by the host response to infection. To examine this possibility, gamma interferon (IFN-gamma) and/or tumor necrosis factor alpha (TNF-alpha) were neutralized in BALB/c mice by...

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

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


    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

  7. Phase I and II studies of the combination of recombinant human interferon-gamma and 5-fluorouracil in patients with advanced colorectal carcinoma.

    Ajani, J A; Rios, A A; Ende, K; Abbruzzese, J L; Edwards, C; Faintuch, J S; Saks, S; Gutterman, J U; Levin, B


    Based on the in vitro and in vivo data suggesting synergistic cytolysis by the combination of 5-fluorouracil and interferon-gamma against a variety of malignant cell lines including a human colon carcinoma cell line (HT-29), we initiated studies in patients with advanced colon or rectal carcinoma. Forty-six patients received 5-fluorouracil as an intravenous injection on days 1-5 and recombinant human interferon-gamma as an intramuscular injection on days 1-14, followed by a rest period of 14 days; courses were repeated every 28 days. In the phase I study, cohorts of two patients received a stepwise dose level increase to achieve the maximum tolerated dose (MTD), at which a total of six patients were studied. The dose levels constituting the MTD were as follows: 5-fluorouracil (500 g/m2/day) and recombinant gamma-interferon (0.5 mg/m2/day). Four patients achieved a partial response in the phase I study. In the phase II study, 30 patients received therapy at the MTD. Among 29 evaluable patients in the phase II study, two patients achieved a partial response. Common toxicities included malaise, fever, anorexia, nausea and vomiting, and diarrhea. Transient severe myelosuppression was common but did not result in significant morbidity. Our data suggest that the combination of 5-fluorouracil and recombinant gamma-interferon did not have the same antitumor effect in patients as it had in the preclinical experiments. PMID:2499663

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

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


    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.

  9. A recombinant DNA vaccine protects mice deficient in the alpha/beta interferon receptor against lethal challenge with Usutu virus.

    Martín-Acebes, Miguel A; Blázquez, Ana-Belén; Cañas-Arranz, Rodrigo; Vázquez-Calvo, Ángela; Merino-Ramos, Teresa; Escribano-Romero, Estela; Sobrino, Francisco; Saiz, Juan-Carlos


    Usutu virus (USUV) is a mosquito-borne flavivirus whose circulation had been confined to Africa since it was first detected in 1959. However, in the last decade USUV has emerged in Europe causing episodes of avian mortality and sporadic severe neuroinvasive infections in humans. Remarkably, adult laboratory mice exhibit limited susceptibility to USUV infection, which has impaired the analysis of the immune responses, thus complicating the evaluation of virus-host interactions and of vaccine candidates against this pathogen. In this work, we showed that mice deficient in the alpha/beta interferon receptor (IFNAR (-/-) mice) were highly susceptible to USUV infection and provided a lethal challenge model for vaccine testing. To validate this infection model, a plasmid DNA vaccine candidate encoding the precursor of membrane (prM) and envelope (E) proteins of USUV was engineered. Transfection of cultured cells with this plasmid resulted in expression of USUV antigens and the assembly and secretion of small virus-like particles also known as recombinant subviral particles (RSPs). A single intramuscular immunization with this plasmid was sufficient to elicit a significant level of protection against challenge with USUV in IFNAR (-/-) mice. The characterization of the humoral response induced revealed that DNA vaccination primed anti-USUV antibodies, including neutralizing antibodies. Overall, these results probe the suitability of IFNAR (-/-) mice as an amenable small animal model for the study of USUV host virus interactions and vaccine testing, as well as the feasibility of DNA-based vaccine strategies for the control of this pathogen. PMID:26993334

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

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