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Sample records for ferret immunoglobulins cytokines

  1. Characterization of antibodies against ferret immunoglobulins, cytokines and CD markers

    DEFF Research Database (Denmark)

    Martel, Cyril Jean-Marie; Aasted, Bent

    2009-01-01

    Ferret IgG and IgM were purified from normal serum, while ferret IgA was purified from bile. The estimated molecular weights of the immunoglobulin gamma, alpha and mu heavy chains were found to be 54 kDa, 69 kDa and 83 kDa, respectively. For immunological (ELISA) quantification of ferret...... immunoglobulins, we identified and characterized polyclonal antibodies towards ferret IgG, IgM and IgA. We also identified 22 monoclonal antibodies (mAbs) raised mostly against human CD markers which cross-reacted with ferret leukocytes. These antibodies were originally specific against human CD8, CD9, CD14, CD18......, CD25, CD29, CD32, CD44, CD61, CD71, CD79b, CD88, CD104, CD172a and mink CD3. Finally, we identified 4 cross-reacting mAbs with specificities against ferret interferon-gamma, TNF-alpha, interleukin-4 and interleukin-8....

  2. Ferret

    CERN Document Server

    Balmain, David

    2008-01-01

    With the introduction of Ferret, Ruby users now have one of the fastest and most flexible search libraries available. And it's surprisingly easy to use. This book will show you how to quickly get up and running with Ferret. You'll learn how to index different document types such as PDF, Microsoft Word, and HTML, as well as how to deal with foreign languages and different character encodings. Ferret describes the Ferret Query Language in detail along with the object-oriented approach to building queries. You will also be introduced to sorting, filtering, and highlighting your search results

  3. New methods and reagents to improve the ferret model for human influenza infections

    DEFF Research Database (Denmark)

    Martel, Cyril Jean-Marie; Kirkeby, Svend; Aasted, Bent

    The ferret has been extensively used to study human influenza infections. However, its value as a model has suffered from the limited set of reagents and methods available for this animal. We have recently tested a large number of monoclonal antibodies cross-reacting with ferret CD markers (CD8, CD......9, CD14, CD18, CD25, CD29, CD32, CD44, CD61, CD71, CD79b, CD88, CD104, CD172a and CD3) and cytokines (interferon-gamma, TNF-alpha, interleukine-4 and interleukine-8) for flow cytometry , as well as polyclonal antibodies cross-reacting with ferret immunoglobulins (IgA, IgG and IgM) for ELISA. Further...... improvements of the model will aim at establishing a reliable RT-PCR for ferret cytokines, as well as investigating the location of influenza receptors and viral particles in the upper and lower respiratory tract via immunohistochemistry...

  4. 1918 H1N1 influenza virus replicates and induces pro-inflammatory cytokine responses in extra-respiratory tissues of ferrets.

    Science.gov (United States)

    de Wit, Emmie; Siegers, Jurre; Cronin, Jacqueline M; Weatherman, Sarah; van den Brand, Judith; Leijten, Lonneke M; van Run, Peter; Begeman, Lineke; van den Ham, Henk-Jan; Andeweg, Arno C; Bushmaker, Trenton; Scott, Dana P; Saturday, Greg; Munster, Vincent J; Feldmann, Heinz; van Riel, Debby

    2018-01-10

    The 1918 Spanish H1N1 influenza pandemic was the most severe recorded influenza pandemic with an estimated 20-50 million deaths worldwide. Even though it is known that influenza viruses can cause extra-respiratory tract complications-which are often severe or even fatal- the potential contribution of extra-respiratory tissues to the pathogenesis of 1918 H1N1 virus infection has not been studied comprehensively. Here, we performed a time course study in ferrets inoculated intranasally with 1918 H1N1 virus, with special emphasis on the involvement of extra-respiratory tissues. Respiratory and extra-respiratory tissues were collected after inoculation for virological, histological and immunological analysis. Infectious virus was detected at high titers in respiratory tissues, and-at lower titers-in most extra-respiratory tissues. Evidence for active virus replication, as indicated by the detection of nucleoprotein by immunohistochemistry, was observed in the respiratory tract, peripheral and central nervous system, and liver. Pro-inflammatory cytokines were upregulated in respiratory tissues, olfactory bulb, spinal cord, liver, heart and pancreas. 1918 H1N1 virus spread to, and induced cytokine responses in tissues outside the respiratory tract, which likely contributed to the severity of infection. Moreover, our data support the suggested link between 1918 H1N1 infection and CNS disease.

  5. The effect of chronic ammonia exposure on acute phase proteins, immunoglobulin and cytokines in laying hens

    Science.gov (United States)

    Ammonia is a potential health hazard to both humans and animals, causing systemic low-grade inflammation based on its levels and durations. The objective of this study was to examine the effect of 45 weeks of exposure to 30 ppm NH3 on the concentrations of acute phase proteins, immunoglobulins and c...

  6. Detection and clinical significance of rheumatoid factor, anti -CCP antibody , immunoglobulin and cytokines in serum of patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Hui-Ya Zhu

    2016-12-01

    Full Text Available Objective: To detect the content of rheumatoid factor, ring citrulline peptide antibody (CCP, immunoglobulin (Ig and cytokines in serum of patients with rheumatoid arthritis (RA and explore the clinical application value of serum indexes for RA diagnosis, treatment and prognostic.Methods: A total of 98 patients with RA were selected, of which 52 cases in the activity and 46 patients in remission, 65 healthy people as controls. Contents of serum RF and Ig (IgM, IgG, IgA in every group were detected by methods of immune scattering turbidimetry respectively; the content of serum anti-CCP antibody and cytokines IL-1β, TNF-α, IFN-γ and IL-4 were measured by methods of enzyme-linked immunosorbent respectively. Change of detection index levels between groups were compared and the correlation between cytokines and RF, anti CCP, Ig and DAS28 score in patients with RA were analyzed. Results: The contents of serum RF, CCP antibody, Ig (IgM and IgG, IgA of RA group (activity and remission were respectively significantly higher than that of the control group (P0.05. The levels of cytokine IL-1β, TNF-α, IFN-γ were positively correlated with RF, CCP antibody, Ig and DAS28 scores in RA activity while which were only positively correlated with DAS28 scores of RA in remission, and the IL-4 level had no significant correlation with other indicators. Conclusions: The detection of levels of RF, CCP antibody, Ig and cytokine for the diagnosis, treatment and prognosis of RA has important reference value.

  7. Cytokines regulate complement receptor immunoglobulin expression and phagocytosis of Candida albicans in human macrophages: A control point in anti-microbial immunity.

    Science.gov (United States)

    Munawara, Usma; Small, Annabelle G; Quach, Alex; Gorgani, Nick N; Abbott, Catherine A; Ferrante, Antonio

    2017-06-22

    Complement Receptor Immunoglobulin (CRIg), selectively expressed by macrophages, plays an important role in innate immunity by promoting phagocytosis of bacteria. Thus modulation of CRIg on macrophages by cytokines can be an important mechanism by which cytokines regulate anti-microbial immunity. The effects of the cytokines, tumor necrosis factor, transforming growth factor-β1, interferon-γ, interleukin (IL)-4, IL-13, IL-10, IL-1β, IL-6, lymphotoxin-α, macrophage-colony stimulating factor (M-CSF) and GM-CSF on CRIg expression were examined in human macrophages. We demonstrated that cytokines regulated the CRIg expression on macrophages during their development from monocytes in culture at the transcriptional level using qPCR and protein by Western blotting. Both CRIg spliced forms (Long and Short), were similarly regulated by cytokines. Direct addition of cytokines to matured CRIg+ macrophages also changed CRIg mRNA expression, suggesting that cytokines control macrophage function via CRIg, at two checkpoints. Interestingly the classical complement receptors, CR3 and CR4 were differentially regulated by cytokines. The changes in CRIg but not CR3/CR4 mRNA expression correlated with ability to phagocytose Candida albicans by macrophages. These findings suggest that CRIg is likely to be a control point in infection and immunity through which cytokines can mediate their effects, and is differentially regulated from CR3 and CR4 by cytokines.

  8. Cytokine and immunoglobulin production by PWM-stimulated peripheral and tumor-infiltrating lymphocytes of undifferentiated nasopharyngeal carcinoma (NPC patients

    Directory of Open Access Journals (Sweden)

    Bouzouita Kamel

    2004-09-01

    Full Text Available Abstract Background Undifferentiated Nasopharyngeal Carcinoma (NPC patients show a characteristic pattern of antibody responses to the Epstein-Barr virus (EBV which is regularly associated with this tumor. However, no EBV-specific cytotoxic activity is detectable by the standard chromium-release assay at both peripheral and intratumoral levels. The mechanisms underlying this discrepancy between the humoral and cellular immune responses in NPC are still unknown, but might be related to an imbalance in immunoregulatory interleukin production. In this report, we investigated the ability of peripheral (PBL and tumor- infiltrating (TIL lymphocytes of undifferentiated NPC patients to produce in vitro three interleukins (IL-2, IL-6, IL-10 and three immunoglobulin isotypes (IgM, IgG, IgA. Methods Lymphocytes from 17 patients and 17 controls were cultured in the presence of Pokeweed mitogen (PWM for 12 days and their culture supernatants were tested for interleukins and immunoglobulins by specific enzyme-linked immunosorbent assays (ELISA. Data were analysed using Student's t-test and probability values below 5% were considered significant. Results The data obtained indicated that TIL of NPC patients produced significantly more IL-2 (p = 0,0002, IL-10 (p = 0,020, IgM (p= 0,0003 and IgG (p Conclusion Taken together, our data reinforce the possibility of an imbalance in immunoregulatory interleukin production in NPC patients. An increased ability to produce cytokines such as IL-10 may underlie the discrepancy between humoral and cellular immune responses characteristic of NPC.

  9. Effects of cold stress on mRNA expression of immunoglobulin and cytokine in the small intestine of broilers.

    Science.gov (United States)

    Zhao, Fu-Qing; Zhang, Zi-Wei; Yao, Hai-Dong; Wang, Liang-Liang; Liu, Tao; Yu, Xian-Yi; Li, Shu; Xu, Shi-Wen

    2013-08-01

    To investigate the effects of cold stress on mRNA expression of immunoglobulin and cytokine in small intestine of broilers, eighty-four 15-day-old male chickens were randomly divided into 12 groups. There were 1 control (25°C) and 5 acute stress groups (under the temperature of 12 ± 1°C) for 1, 3, 6, 12 and 24h, 3 control (25°C) and 3 chronic cold stress groups (under the temperature of 12 ± 1°C) for 5, 10, and 20d. The mRNA expression levels of IL-2, IL-4, IL-7, IL-10, IL-17, IFN-γ, IgA, IgM, IgG, plgR, and TGF-β4 in duodenum, jejunum and ileum were detected by real-time PCR. The results showed that expression levels of IgM, IgA, IgG, plgR and IL-7 had an increased tendency in acute and chronic cold stress, especially plgR that was markedly increased in the duodenum than jejunum and ileum in the acute cold stress. In addition, the mRNA expression levels of IL-2, IFN-γ, IL-4, IL-17 and TGF-β4 had a first increased then decreased tendency in acute and chronic cold stress groups, however, expression levels of IL-4 were higher in the stress groups than control groups. The histopathological detect showed that issues in cold stress group was seriously injured. These results demonstrated that cold stress could cause the change of immune function in chicken intestinal. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Dynamics of cytokines and immunoglobulins serum profiles in primary and secondary Cryptosporidium parvum infection: usefulness of Luminex® xMAP technology.

    Science.gov (United States)

    Codices, Vera; Martins, Catarina; Novo, Carlos; de Sousa, Bruno; Lopes, Ângela; Borrego, Miguel; Matos, Olga

    2013-01-01

    Infection by Cryptosporidium parvum triggers a complex array of innate and adaptive cell mediated immune response, playing an important role in controlling the infection. To date, there are no studies applying the Luminex® xMAP technology to determine profiles of cytokines and immunoglobulins in the context of an infection by C. parvum. In this study, we analyzed these immune mediators in the serum of immunocompetent mice inoculated with C. parvum oocysts, using Luminex, to understand how the immune system responds to an infection by this parasite. Animal sera were also analyzed by ELISA to determine the expressed immunoglobulin isotype profile, and compare the obtained trend with data obtained by Luminex. Specific-pathogen-free BALB/C mice were inoculated with oocysts of C. parvum at days 0 and 22. Peripheral blood was aseptically collected from sacrificed mice on several time points, and immune mediators were evaluated in serum samples. Infection was confirmed by the presence of C. parvum DNA in feces by a nested-PCR assay (60-kDa glycoprotein). Luminex results showed predominance in the secretion of IgG1 and IgG2a, confirmed by ELISA, which also showed that IgG1 is the major immunoglobulin isotype produced during the infection. The analysis of cytokines suggests a preferential Th(1) over the Th(2) response, with increased production of TNF-α, IFN-γ and GM-CSF. This work contributed to a better understanding of the immune response to the infection by C. parvum, as well as demonstrated the advantage of Luminex® xMAP technology to study immune mediators, using small sample volumes. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Curative effect of minimally invasive surgery on palmar and foot hyperhidrosis and its influence on serum-related cytokines and immunoglobulins.

    Science.gov (United States)

    Li, Wei Xi; Li, Yong Kun; Lin, Hai Tao

    2018-04-01

    The curative effect of minimally invasive surgery on palmar and foot hyperhidrosis and its influence on serum-related cytokines and immunoglobulins were investigated. Seventy-six patients with palmar and foot hyperhidrosis admitted to Yunnan University Hospital from August 2014 to July 2016 were selected and randomly divided into control group (n=38) and observation group (n=38) using a random number table. Patients in control group received drug therapy, while those in observation group underwent laparoscopic thoracic-4 sympathetic chain combined with thoracic-3 branch amputation. The therapeutic effects of patients in the two groups were compared. The levels of serum C-reactive protein (CRP), interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α) of patients in the two groups were measured by enzyme-linked immunosorbent assay (ELISA) before treatment and at one week after treatment. The levels of immunoglobulin G (IgG), IgA and IgM were detected by immunoturbidimetry. The quality of life (QOL) in patients was evaluated by quality-of-life index (iQOL) before and after treatment. The total effective rate in the observation group was significantly higher than that in the control group (P0.05). At one week after treatment, IgG, IgM and IgA levels of patients in the two groups were remarkably increased (P0.05). After treatment, the iQQL scores of patients in the two groups were significantly decreased, and iQQL score in observation group was decreased more significantly compared with that in control group (P<0.05). Compared with drug therapy, minimally invasive surgery is more effective in the treatment of palmar and foot hyperhidrosis with smaller trauma and inflammatory reaction, and it has less influence on serum immunoglobulin levels, which is conducive to the rehabilitation of patients.

  12. Intravenous immunoglobulin treatment of the post-polio syndrome: sustained effects on quality of life variables and cytokine expression after one year follow up

    Directory of Open Access Journals (Sweden)

    Gonzalez Henrik

    2012-07-01

    Full Text Available Abstract Background Expression of inflammatory cytokines in cerebrospinal fluid (CSF has led to the hypothesis of intrathecal chronic inflammation to explain the denervation observed in post-polio syndrome (PPS. It has been shown that therapy with intravenous immunoglobulin (IVIG improves physical performance and dampens down the inflammatory process at 6 months in PPS patients. We here examined the effects of IVIG on cytokine expression and clinical outcome one year after IVIG treatment. Methods From a previous study with 135 PPS patients included, 41 patients were further evaluated before un-blinding for one year (21 placebo and 20 treated with IVIG, Xepol® 50 mg/ml, and were assessed for clinical variables by performing the Short Form-36 survey (SF-36 questionnaire assessment, the 6 minute walk distance test (6MWT and registering pain level by Visual Analogue Scale (VAS after IVIG treatment. A separate cohort of 37 PPS patients went through lumbar puncture (LP at baseline and 20 patients, treated with IVIG, repeated the LP one year later. Thirty patients affected with other neurological diseases (OND were used as control group. Inflammatory cytokines TNF, TGFβ, IFNγ, IL-23, IL-13 and IL-10 were measured in blood cells and CSF cells with RT-PCR. Results Scores of the physical components of SF-36 were significantly higher at the one year follow up time-point in the IVIG-treated patients when compared to baseline as well as to the control subjects. Pain VAS score and 6MWT improved significantly in the IVIG-treated patients when compared with baseline Relative expression of TNF and IFN-γ in both PBMCs and CSF from PPS patients were increased compared to OND subjects at baseline (p  Conclusions IVIG has effects on relevant QoL variables and inflammatory cytokines up to one year in patients with PPS. This gives a basis for scheduling IVIG in upcoming trials with this therapy.

  13. [Study of immunoglobulins, proinflammatory cytokines, lymphoproliferation and phagocytosis in peripheral blood of healthy young people exposed to different levels of atmospheric pollution].

    Science.gov (United States)

    Moreno Ramíez, Everardo; Hernández Urzúa, Miguel Angel; González Villegas, Ana Cecilia; Casas Solís, Josefina; Zaitseva, Galina

    2006-01-01

    Urban environmental pollutants, resulting from the inadequate control in the industries and from the use of vehicles, still represent a great danger for millions of people all around the world. We made a study in healthy young people without family history of atopy that lived in Guadalajara's downtown, as well as in another group of young people who lived in a rural area. According to the census of the year 2000, Guadalajara city has a population of 4 million habitants, and a vehicle number of about a million. The immunological parameters that we studied were: IgG, IgA and IgM immunoglobulins by nephelometry, serum levels of proinflammatory cytokines IL-6, IL-1alpha, IL1-beta and TNF-alpha by ELISAs test, and the phagocytic index in polymorphonuclears. The atmospheric parameters were: NO2, O3, SO2, CO and the suspended particles that were less than 10 micrometers (PM10). These parameters were obtained from a mobile unit found at the Instituto de Astronomia y Meteorología de la Universidad de Guadalajara, and from an automatic station of environmental monitoring. It stands out the high concentrations of NO2 and PM10, which in several occasions were over the standards established by the WHO. IgG, IgA and IgM immunoglobulins were lower in the subjects living in the city that in those who lived in the rural area. Phagocytic index in polymorphonuclears, as well as IL-1alpha levels were higher in the city group, though we did not find a significant difference in the immunological parameters analyzed in the studied groups. Environmental pollution levels found at Guadalajara's downtown does not modify the immunological parameters studied in the peripheral blood of healthy young people. This shows that this group of population is less vulnerable than others to the exposition of moderate levels of urban air pollution.

  14. Intravenous immunoglobulin treatment of the post-polio syndrome: sustained effects on quality of life variables and cytokine expression after one year follow up.

    Science.gov (United States)

    Gonzalez, Henrik; Khademi, Mohsen; Borg, Kristian; Olsson, Tomas

    2012-07-09

    Expression of inflammatory cytokines in cerebrospinal fluid (CSF) has led to the hypothesis of intrathecal chronic inflammation to explain the denervation observed in post-polio syndrome (PPS). It has been shown that therapy with intravenous immunoglobulin (IVIG) improves physical performance and dampens down the inflammatory process at 6 months in PPS patients. We here examined the effects of IVIG on cytokine expression and clinical outcome one year after IVIG treatment. From a previous study with 135 PPS patients included, 41 patients were further evaluated before un-blinding for one year (21 placebo and 20 treated with IVIG, Xepol® 50 mg/ml), and were assessed for clinical variables by performing the Short Form-36 survey (SF-36) questionnaire assessment, the 6 minute walk distance test (6MWT) and registering pain level by Visual Analogue Scale (VAS) after IVIG treatment. A separate cohort of 37 PPS patients went through lumbar puncture (LP) at baseline and 20 patients, treated with IVIG, repeated the LP one year later. Thirty patients affected with other neurological diseases (OND) were used as control group. Inflammatory cytokines TNF, TGFβ, IFNγ, IL-23, IL-13 and IL-10 were measured in blood cells and CSF cells with RT-PCR. Scores of the physical components of SF-36 were significantly higher at the one year follow up time-point in the IVIG-treated patients when compared to baseline as well as to the control subjects. Pain VAS score and 6MWT improved significantly in the IVIG-treated patients when compared with baseline Relative expression of TNF and IFN-γ in both PBMCs and CSF from PPS patients were increased compared to OND subjects at baseline (p < 0.05). One year after IVIG-treatment a decreased expression of IFN-γ and IL23 was found in CSF of PPS patients, while anti-inflammatory IL-13 was increased (p < 0.05). IVIG has effects on relevant QoL variables and inflammatory cytokines up to one year in patients with PPS. This gives a basis for

  15. Probiotic Dahi containing Lactobacillus acidophilus and Bifidobacterium bifidum modulates immunoglobulin levels and cytokines expression in whey proteins sensitised mice.

    Science.gov (United States)

    Shandilya, Umesh Kumar; Sharma, Ankita; Kapila, Rajeev; Kansal, Vinod Kumar

    2016-07-01

    Cow milk allergy is the most common food allergy in children. So far, no effective treatment is available to prevent or cure food allergy. This study investigated whether orally administrated probiotics could suppress sensitisation in whey proteins (WP)-induced allergy mouse model. Two types of probiotic Dahi were prepared by co-culturing Dahi bacteria (Lactococcus lactis ssp. cremoris NCDC-86 and Lactococcus lactis ssp. lactis biovar diacetylactis NCDC-60) along with selected strain of Lactobacillus acidophilus LaVK2 and Bifidobacterium bifidum BbVK3. Mice were fed with probiotic Dahi (La-Dahi and LaBb-Dahi) from 7 days before sensitisation with WP, respectively, in addition to milk protein-free basal diet, and control group received no supplements. Feeding of probiotic Dahi suppressed the elevation of whey proteins-specific IgE and IgG response of WP-sensitised mice. In addition, sIgA levels were significantly (P mice fed with La-Dahi. Production of T helper (Th)-1 cell-specific cytokines, i.e. interferon-γ (IFN-γ), interleukin (IL)-12, and IL-10 increased, while Th2-specific cytokines, i.e. IL-4 decreased in the supernatant of cultured splenocytes collected from mice fed with probiotic Dahi as compared to the other groups. Moreover, the splenic mRNA levels of IFN-γ, interleukin-10 were found to be significantly increased, while that of IL-4 decreased significantly in La-Dahi groups, as compared to control groups. Results of the present study indicate that probiotic Dahi skewed Th2-specific immune response towards Th1-specific response and suppressed IgE in serum. Collectively, this study shows the potential use of probiotics intervention in reducing the allergic response to whey proteins in mice. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  16. Effects of an illicit cocktail on serum immunoglobulins, lymphocyte proliferation and cytokine gene expression in the veal calf

    International Nuclear Information System (INIS)

    Cantiello, Michela; Carletti, Monica; Cannizzo, Francesca T.; Nebbia, Carlo; Bellino, Claudio; Pie, Sandrine; Oswald, Isabelle P.; Bollo, Enrico; Dacasto, Mauro

    2007-01-01

    At the European Union level, the use of growth promoters (GPs) in cattle and other food-producing species is forbidden; nonetheless, the illicit use of anabolic hormones, β-agonists and corticosteroids, often administered in cocktails at lower concentrations to overcome control procedures, is still of public concern. The immune system (IS) is a multicomponent system that provide a coordinated response toward infectious diseases, not self-neoplasms and xenobiotics; in this respect, some GPs have been proved able to cause both morphological alterations in lymphoid organs and a modulating effect upon some immunological parameters. Therefore, in the present study the effects of an illicit cocktail upon the cattle IS functions were investigated by using some common endpoints adopted for the IS testing in humans. Twelve cross-bred male veal calves were divided in two experimental groups (n = 6); the first group was administered a cocktail of 17β-oestradiol (10 mg, 3 im injections at 17 days intervals), clenbuterol (20 μg kg -1 , per os for 40 days) and dexamethasone (4 mg per os for 6 days and, then, 5 mg for further 6 days) for a total of 55 days. The second one was used as control. Blood sampling were taken at T 0 and after 15 (T 1 ), 34 (T 2 ), 48 (T 3 ) days as well as the day before slaughtering (T 4 ). Immune endpoints considered were the thymus weight, the serum immunoglobulin G (IgG) and M (IgM) levels, the lymphocyte proliferation assay and the lymphocyte interleukins 1β and 8, tumour necrosis factor α and interferon γ (IFN-γ) gene expression levels. The administration of the illicit cocktail resulted in: (a) a reduction (P 1 , whereas in the second part of the study increasing levels (P 2 and T 4 for IgM and IgG, respectively) were recorded; (c) an overall reduction (P 1 ; in phytohaemagglutinin-stimulated cells, such a decrease was delayed up to T 2 (P 1 and T 2 . Taken together, present data suggest that GPs, even given in cocktails at sub

  17. Ferret Workflow Anomaly Detection System

    National Research Council Canada - National Science Library

    Smith, Timothy J; Bryant, Stephany

    2005-01-01

    The Ferret workflow anomaly detection system project 2003-2004 has provided validation and anomaly detection in accredited workflows in secure knowledge management systems through the use of continuous, automated audits...

  18. Cytokine Regulation Immunoglobulin Isotype Production

    Science.gov (United States)

    1994-11-08

    digestion-circularization polymerase chain reaction DNA - deoxyribonucleic acid XXII EAE - experimental autoimmune encephalomyelitis ECF eosinophil...its immunoinhibitory properties (216,217). Further, In experimental autoimmune encephalomyelitis (EAE) the secretion of TGF-~ by CD8+ suppressor T...dicarded and the cell pellet was resu spended in a sterile filtered complement cocktail containing guinea pig complement (GibcoBRL, 38 Long

  19. Immunoglobulin genes

    National Research Council Canada - National Science Library

    Honjo, T; Alt, F. W; Rabbitts, T. H

    1989-01-01

    ... Cataloguing in Publication Data Immunoglobulin genes 1. Vertebrates. Immunoglobulins 1. Honjo, T. II. Alt, F.W. III. Rabbitts, T.H. 612'. 118223 ISBN 0-12-354865-9 This book is printed on acid-free paper ( T...

  20. Killer Immunoglobulin-like Receptors (KIR) haplogroups A and B track with Natural Killer Cells and Cytokine Profile in Aged Subjects: Observations from Octo/Nonagenarians in the Belfast Elderly Longitudinal Free-living Aging STudy (BELFAST)

    Science.gov (United States)

    2013-01-01

    Background Natural Killer Cells (NK) play an important role in detection and elimination of virus-infected, damaged or cancer cells. NK cell function is guided by expression of Killer Immunoglobulin-like Receptors (KIRs) and contributed to by the cytokine milieu. KIR molecules are grouped on NK cells into stimulatory and inhibitory KIR haplotypes A and B, through which NKs sense and tolerate HLA self-antigens or up-regulate the NK-cytotoxic response to cells with altered HLA self-antigens, damaged by viruses or tumours. We have previously described increased numbers of NK and NK-related subsets in association with sIL-2R cytokine serum levels in BELFAST octo/nonagenarians. We hypothesised that changes in KIR A and B haplotype gene frequencies could explain the increased cytokine profiles and NK compartments previously described in Belfast Elderly Longitudinal Free-living Aging STudy (BELFAST) octo/nonagenarians, who show evidence of ageing well. Results In the BELFAST study, 24% of octo/nonagenarians carried the KIR A haplotype and 76% KIR B haplotype with no differences for KIR A haplogroup frequency between male or female subjects (23% v 24%; p=0.88) or for KIR B haplogroup (77% v 76%; p=0.99). Octo/nonagenarian KIR A haplotype carriers showed increased NK numbers and percentage compared to Group B KIR subjects (p=0.003; p=0.016 respectively). There were no KIR A/ B haplogroup-associated changes for related CD57+CD8 (high or low) subsets. Using logistic regression, KIR B carriers were predicted to have higher IL-12 cytokine levels compared to KIR A carriers by about 3% (OR 1.03, confidence limits CI 0.99–1.09; p=0.027) and 14% higher levels for TGF-β (active), a cytokine with an anti-inflammatory role, (OR 1.14, confidence limits CI 0.99–1.09; p=0.002). Conclusion In this observational study, BELFAST octo/nonagenarians carrying KIR A haplotype showed higher NK cell numbers and percentage compared to KIR B carriers. Conversely, KIR B haplotype carriers, with

  1. SOMATOTOPIC ORGANIZATION OF FERRET THALAMUS

    Directory of Open Access Journals (Sweden)

    Mario eVázquez García

    2014-11-01

    Full Text Available The stereotaxic reference marks of ferret skull have large variability and the reference point for stereotaxic experiments in ferret brain is difficult to define. Here, using extracellular single-unit recordings, we studied the somatotopic organization of cutaneous receptive fields in the ventroposterior medial (VPM and the ventral posterolateral (VPL nuclei of the ferret thalamus. The mechanical stimulation of the skin was done through air puffs. The skull was positioned according to Horsley-Clarke coordinate system. Most of the neurons responding to face skin stimulation were located +7 - +9 mm anterior, 2 – 3.9 mm lateral and 7-9.6 mm from cortical surface, whereas those responding to body skin stimulation were located +7 - +10 mm anterior, 3.3 - 5.5 mm lateral and 6.7 -10 mm from cortical surface. Out of 90 thalamic neurons recorded in this study, 58 responded to the body and the other neurons to the face stimulation. All neurons responded with spikes to stimulus onset, 37 % of neurons responded only to stimuli onset and offset and 22 % neurons fired tonically throughout stimulating epoch. The whiskers representation was located in the middle of the VPM nucleus, whereas those of the tongue, nose, bridge of the nose, supraorbital areas, upper and lower lips, and lower jaw were surrounding the whiskers representation. Within the VPL nucleus there was a clear topological correspondence from forelimb to hindlimb in the medial-to-lateral direction. Our findings indicate the whiskers representation in VPM or the forelimb-hindlimb representation in the VPL nucleus can be considered as a reliable reference in the ferret thalamus.

  2. Somatotopic organization of ferret thalamus

    Science.gov (United States)

    Vázquez-García, Mario; Wallman, Marie-Josée; Timofeev, Igor

    2014-01-01

    The stereotaxic reference marks of ferret skull have large variability and the reference point for stereotaxic experiments in ferret brain is difficult to define. Here, using extracellular single-unit recordings, we studied the somatotopic organization of cutaneous receptive fields in the ventroposterior medial (VPM) and the ventral posterolateral (VPL) nuclei of the ferret thalamus. The mechanical stimulation of the skin was done through air puffs. The skull was positioned according to Horsley-Clarke coordinate system. Most of the neurons responding to face skin stimulation were located +7–+9 mm anterior, 2–3.9 mm lateral and 7–9.6 mm from cortical surface, whereas those responding to body skin stimulation were located +7–+10 mm anterior, 3.3–5.5 mm lateral and 6.7–10 mm from cortical surface. Out of 90 thalamic neurons recorded in this study, 58 responded to the body and the other neurons to the face stimulation. All neurons responded with spikes to stimulus onset, 37% of neurons responded only to stimuli onset and offset and 22% neurons fired tonically throughout stimulating epoch. The whiskers representation was located in the middle of the VPM nucleus, whereas those of the tongue, nose, bridge of the nose, supraorbital areas, upper and lower lips, and lower jaw were surrounding the whiskers representation. Within the VPL nucleus there was a clear topological correspondence from forelimb to hindlimb in the medial-to-lateral direction. Our findings indicate the whiskers representation in VPM or the forelimb-hindlimb representation in the VPL nucleus can be considered as a reliable reference in the ferret thalamus. PMID:25484859

  3. Ferret Oncology : Diseases, Diagnostics, and Therapeutics

    NARCIS (Netherlands)

    Schoemaker, Nico J

    Neoplastic disease is common in ferrets. Approximately half of all tumors diagnosed in ferrets are located in the endocrine or hemolymphatic system. Many factors may influence the choice of treatment. Medical management of adrenal tumors has a greater disease-free period compared to adrenalectomy.

  4. The effect of lead exposure on tracheal responsiveness to methacholine and ovalbumin, total and differential white blood cells count, and serum levels of immunoglobulin E, histamine, and cytokines in guinea pigs.

    Science.gov (United States)

    Farkhondeh, T; Boskabady, M H; Jalali, S; Bayrami, G

    2014-03-01

    The effect of exposure to inhaled lead acetate in guinea pigs was evaluated. The present study comprised of five groups of guinea pigs including control (C), sensitized to ovalbumin (OA; S) and three groups exposed to 0.1, 0.2, and 0.4 M inhaled lead (Pb; n = 6 for each group). Tracheal responsiveness to methacholine and OA, total and differential white blood cells (WBCs) count in lung lavage, serum levels of cytokines (interferon γ (IFN-γ) and interleukin 4 (IL-4)), histamines, and immunoglobulin E (IgE), and Pb concentration in lung were measured. Tracheal responsiveness to methacholine, OA, total and differential WBC types as well as IL-4, IFN-γ, histamine, and IgE were significantly increased but IFN-γ/IL-4 were significantly decreased in sensitized animals as well as those exposed to high Pb concentrations when compared with the control group (from p < 0.05 to p < 0.001). In addition, there was not a significant difference in most measured values between animals exposed to high Pb concentration and group S. The Pb concentration in lung tissues of animals exposed to all three Pb concentrations was significantly higher than that of group C (p < 0.001 for all cases).These results showed that inhaled lead acetate exposure can induce lung inflammatory changes similar to sensitized animals. Therefore, exposure to environmental Pb pollution may cause asthma-like changes.

  5. Immunoglobulin M

    DEFF Research Database (Denmark)

    Pleass, Richard J; Moore, Shona C; Stevenson, Liz

    2016-01-01

    Immunoglobulin M (IgM) is an ancient antibody class that is found in all vertebrates, with the exception of coelacanths, and is indispensable in both innate and adaptive immunity. The equally ancient human malaria parasite, Plasmodium falciparum, formed an intimate relationship with IgM with whic...

  6. Perception and Neural Coding of Harmonic Fusion in Ferrets

    National Research Council Canada - National Science Library

    Kalluri, Sridhar; Shamma, Shihab

    2004-01-01

    .... Experiment 1 tested whether ferrets automatically fuse harmonic complex tones. In baseline sessions, three ferrets were trained to detect a pure tone terminating a sequence of inharmonic complex tones...

  7. A test of mink microsatellite markers in the ferret

    DEFF Research Database (Denmark)

    Anistoroaei, Razvan Marian; Christensen, Knud

    2006-01-01

    markers from American mink were tested in the ferret, under the same conditions as for the mink. Of the 59, 43 off them (73.5 %) amplified a ferret sequence; 5 amplification products differed in size from the respective mink sequences. Ten amplified fragments from ferret were sequenced. The sequences...

  8. Cold exposure down-regulates immune response pathways in ferret aortic perivascular adipose tissue.

    Science.gov (United States)

    Reynés, Bàrbara; van Schothorst, Evert M; García-Ruiz, Estefanía; Keijer, Jaap; Palou, Andreu; Oliver, Paula

    2017-05-03

    Perivascular adipose tissue (PVAT) surrounds blood vessels and releases paracrine factors, such as cytokines, which regulate local inflammation. The inflammatory state of PVAT has an important role in vascular disease; a pro-inflammatory state has been related with atherosclerosis development, whereas an anti-inflammatory one is protective. Cold exposure beneficially affects immune responses and, could thus impact the pathogenesis of cardiovascular diseases. In this study, we investigated the effects of one-week of cold exposure at 4°C of ferrets on aortic PVAT (aPVAT) versus subcutaneous adipose tissue. Ferrets were used because of the similarity of their adipose tissues to those of humans. A ferret-specific Agilent microarray was designed to cover the complete ferret genome and global gene expression analysis was performed. The data showed that cold exposure altered gene expression mainly in aPVAT. Most of the regulated genes were associated with cell cycle, immune response and gene expression regulation, and were mainly down-regulated. Regarding the effects on immune response, cold acclimation decreased the expression of genes involved in antigen recognition and presentation, cytokine signalling and immune system maturation and activation. This immunosuppressive gene expression pattern was depot-specific, as it was not observed in the inguinal subcutaneous depot. Interestingly, this depression in immune response related genes was also evident in peripheral blood mononuclear cells (PBMC). In conclusion, these results reveal that cold acclimation produces an inhibition of immune response-related pathways in aPVAT, reflected in PBMC, indicative of an anti-inflammatory response, which can potentially be exploited for the enhancement or maintenance of cardiovascular health.

  9. Evidence-Based Advances in Ferret Medicine.

    Science.gov (United States)

    Huynh, Minh; Chassang, Lucile; Zoller, Graham

    2017-09-01

    This literature review covers approximately 35 years of veterinary medicine. This article develops the current state of knowledge in pet ferret medicine regarding the most common diseases according to evidence-based data and gives insight into further axis of research. Literature review was conducted through identification of keywords (title + ferret) with Web-based database searching. To appreciate the methodological quality and the level of evidence of each article included in the review, full-text versions were reviewed and questions addressed in the articles were formulated. Analysis of the articles' content was performed by the authors, and relevant clinical information was extracted. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. FIIND: Ferret Interactive Integrated Neurodevelopment Atlas

    Directory of Open Access Journals (Sweden)

    Roberto Toro

    2018-03-01

    Full Text Available The first days after birth in ferrets provide a privileged view of the development of a complex mammalian brain. Unlike mice, ferrets develop a rich pattern of deep neocortical folds and cortico- cortical connections. Unlike humans and other primates, whose brains are well differentiated and folded at birth, ferrets are born with a very immature and completely smooth neocortex: folds, neocortical regionalisation and cortico-cortical connectivity develop in ferrets during the first postnatal days. After a period of fast neocortical expansion, during which brain volume increases by up to a factor of 4 in 2 weeks, the ferret brain reaches its adult volume at about 6 weeks of age. Ferrets could thus become a major animal model to investigate the neurobiological correlates of the phenomena observed in human neuroimaging. Many of these phenomena, such as the relationship between brain folding, cortico-cortical connectivity and neocortical regionalisation cannot be investigated in mice, but could be investigated in ferrets. Our aim is to provide the research community with a detailed description of the development of a complex brain, necessary to better understand the nature of human neuroimaging data, create models of brain development, or analyse the relationship between multiple spatial scales. We have already started a project to constitute an open, collaborative atlas of ferret brain development, integrating multi-modal and multi-scale data. We have acquired data for 28 ferrets (4 animals per time point from P0 to adults, using high-resolution MRI and diffusion tensor imaging (DTI. We have developed an open-source pipeline to segment and produce – online – 3D reconstructions of brain MRI data. We propose to process the brains of 16 of our specimens (from P0 to P16 using high-throughput 3D histology, staining for cytoarchitectonic landmarks, neuronal progenitors and neurogenesis. This would allow us to relate the MRI data that we have already

  11. Distichiasis in a ferret (Mustela putorius furo)

    NARCIS (Netherlands)

    Verboven, CAPM|info:eu-repo/dai/nl/413490548; Djajadiningrat-Laanen, S.C.|info:eu-repo/dai/nl/304830852; Kitslaar, W.J.P.; Grinwis, G.C.M.|info:eu-repo/dai/nl/141470909; Schoemaker, N.J.|info:eu-repo/dai/nl/274147599; Boevé, M.H.|info:eu-repo/dai/nl/073931187

    A 4-year-old intact male ferret was presented to the Ophthalmology Service of the Department of Clinical Sciences of Companion Animals of Utrecht University with chronic blepharospasm, epiphora, and conjunctivitis of the right eye. Examination of the eye revealed mild conjunctivitis and three hairs

  12. Atrial septal defect in a ferret

    NARCIS (Netherlands)

    van Schaik-Gerritsen, K.M.; Schoemaker, N.J.; Kik, M.J.L.; Beijerink, N.J.

    2013-01-01

    Abstract A 2-year-old, male castrated ferret (Mustela putorius furo) was presented with progressive abdominal distention and loss of muscle mass despite normal appetite. Physical examination findings included pale mucous membranes, a prolonged capillary refill time, a pulse rate greater than 300

  13. Habitat preferences and intraspecific competition in black-footed ferrets

    Science.gov (United States)

    Biggins, Dean E.; Godbey, Jerry L.; Matchett, Marc R.; Livieri, Travis M.

    2006-01-01

    We used radio-telemetry data (28,560 positional fixes) collected on 153 black-footed ferrets (Mustela nigripes) to (1) reexamine the assumed obligate relationship of these ferrets to prairie dogs (Cynomys spp.), (2) investigate habitat preferences of ferrets at a small scale (1 year (P = 0.048). Also, preference was stronger for wild-born young ferrets than for young captive-born ferrets released to augment the wild population (P = 0.040). This additional evidence for competition among ferrets, and for an advantage of prior residency, raises conservation concerns. The energetics-based model commonly used to predict ferret densities at reintroduction sites does not consider competition, which likely leads to overestimation of the densities of ferrets attainable in high-quality habitat. During sequential releases of ferrets, prior residency may handicap success of newcomers, even though the latter may have higher potential fitness. Although the manner of initial colonization of available habitat by blackfooted ferrets, and their subsequent competition for it, was suggestive of an ideal despotic distribution, we did not assess effects of prey density or burrow density on fitness.

  14. Congenital abnormalities of the vertebral column in ferrets.

    Science.gov (United States)

    Proks, Pavel; Stehlik, Ladislav; Paninarova, Michaela; Irova, Katarina; Hauptman, Karel; Jekl, Vladimir

    2015-01-01

    Vertebral column pathologies requiring surgical intervention have been described in pet ferrets, however little information is available on the normal vertebral formula and congenital variants in this species. The purpose of this retrospective study was to describe vertebral formulas and prevalence of congenital vertebral anomalies in a sample of pet ferrets. Radiographs of 172 pet ferrets (96 males and 76 females) were included in this retrospective study. In 143 ferrets (83.14%), five different formulas of the vertebral column were recorded with normal morphology of vertebrae (rib attachment included) but with a variable number of thoracic (Th), lumbar (L), and sacral (S) vertebrae. The number of cervical (C) vertebrae was constant in all examined animals. Observed vertebral formulas were C7/Th14/L6/S3 (51.74%), C7/Th14/L6/S4 (22.10%), C7/Th14/L7/S3 (6.98%), C7/Th15/L6/S3 (1.74%), and C7/Th15/L6/S4 (0.58%). Formula C7/Th14/L6/S4 was significantly more common in males than in females (P < 0.05). Congenital spinal abnormalities were found in 29 ferrets (16.86%), mostly localized in the thoracolumbar and lumbosacral regions. The cervical region was affected in only one case. Transitional vertebrae represented the most common congenital abnormalities (26 ferrets) in the thoracolumbar (13 ferrets) and lumbosacral regions (10 ferrets) or simultaneously in both regions (three ferrets). Other vertebral anomalies included block (two ferrets) and wedge vertebra (one ferret). Spina bifida was not detected. Findings from the current study indicated that vertebral formulas may vary in ferrets and congenital abnormalities are common. This should be taken into consideration for surgical planning. © 2014 American College of Veterinary Radiology.

  15. Ferret respiratory system: clinical anatomy, physiology, and disease.

    Science.gov (United States)

    Johnson-Delaney, Cathy A; Orosz, Susan E

    2011-05-01

    The upper and lower respiratory tracts of ferrets have several similarities to humans, and therefore have been used as a research model for respiratory function. This article describes the clinical anatomy and physiology, and common respiratory diseases of the ferret. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Metagenomic Analysis of the Ferret Fecal Viral Flora

    NARCIS (Netherlands)

    S.L. Smits (Saskia); V.S. Raj (Stalin); M. Oduber (Minoushka); C.M.E. Schapendonk (Claudia); R. Bodewes (Rogier); L.B.V. Provacia (Lisette); K.J. Stittelaar (Koert); A.D.M.E. Osterhaus (Albert); B.L. Haagmans (Bart)

    2013-01-01

    textabstractFerrets are widely used as a small animal model for a number of viral infections, including influenza A virus and SARS coronavirus. To further analyze the microbiological status of ferrets, their fecal viral flora was studied using a metagenomics approach. Novel viruses from the families

  17. Crossmodal integration improves sensory detection thresholds in the ferret.

    Directory of Open Access Journals (Sweden)

    Karl J Hollensteiner

    Full Text Available During the last two decades ferrets (Mustela putorius have been established as a highly efficient animal model in different fields in neuroscience. Here we asked whether ferrets integrate sensory information according to the same principles established for other species. Since only few methods and protocols are available for behaving ferrets we developed a head-free, body-restrained approach allowing a standardized stimulation position and the utilization of the ferret's natural response behavior. We established a behavioral paradigm to test audiovisual integration in the ferret. Animals had to detect a brief auditory and/or visual stimulus presented either left or right from their midline. We first determined detection thresholds for auditory amplitude and visual contrast. In a second step, we combined both modalities and compared psychometric fits and the reaction times between all conditions. We employed Maximum Likelihood Estimation (MLE to model bimodal psychometric curves and to investigate whether ferrets integrate modalities in an optimal manner. Furthermore, to test for a redundant signal effect we pooled the reaction times of all animals to calculate a race model. We observed that bimodal detection thresholds were reduced and reaction times were faster in the bimodal compared to unimodal conditions. The race model and MLE modeling showed that ferrets integrate modalities in a statistically optimal fashion. Taken together, the data indicate that principles of multisensory integration previously demonstrated in other species also apply to crossmodal processing in the ferret.

  18. Immunoglobulins in Cerebrospinal Fluid

    DEFF Research Database (Denmark)

    Sellebjerg, Finn Thorup

    2015-01-01

    The assessment of intrathecally synthesised immunoglobulin is an important part of routine cerebrospinal fl uid (CSF) analysis. Immunoglobulins can be detected in normal CSF and are derived from plasma. The appearance of immunoglobulins in normal CSF is readily explained by size-dependent diffusion...

  19. Oncology of the ferret (Mustela putorius furo)

    International Nuclear Information System (INIS)

    Bunel Le Coz, Bertrand Jacques Thierry

    2006-01-01

    Ferret oncology is in full evolution. Many types of tumors are mentioned. They affect all the systems of the organism: the endocrine, hemo-lymphatic, integument, digestive, reproductive, musculoskeletal, cardiovascular, nervous, urinary or respiratory systems. Insulinoma, adrenocortical tumors and lymphoma are the three mostly seen tumors. Complementary examination have been developed too. CBC, biochemistry, radiography and ultrasonography can now be completed by cytology, immunohistochemistry, endoscopies, scan, I.R.M. or scintigraphy. Treatments such as surgery, chemotherapy or radiotherapy can be associated. They allow recovery or, if not a palliative solution. (author) [fr

  20. Whole body lymphangioscintigraphy in ferrets chronically infected with Brugia malayi

    Energy Technology Data Exchange (ETDEWEB)

    Witte, M.; McNeill, G.; Crandall, C.; Case, T.; Witte, C.; Crandall, R.; Hall, J.; Williams, W.

    1988-12-01

    Whole body lymphangioscintigraphy was performed after intradermal injection of /sup 99m/technetium human serum albumin or antimony colloid in the distal hindlimbs and forelimbs of ferrets chronically infected with Brugia malayi. The findings were compared with control ferrets and those with surgical interruption of the iliac lymphatics. While only one infected ferret manifested chronic hindlimb lymphedema, all exhibited delayed transport of radioisotope from the hindpaw with obstruction in the groin, poor or absent visualization of central lymphatic channels and regional lymph nodes, a picture similar to that following surgically induced lymphatic obstruction. In control ferrets, there was prompt visualization of peripheral lymphatic channels and regional lymph nodes with sharper and more extensive channel visualization after radiolabeled albumin and more intense sustained nodal visualization after radiolabeled antimony colloid. This noninvasive technique provides a readily repeatable investigative tool adaptable to small animals to study the evolution of lymphatic filariasis and other conditions associated with lymphatic obstruction.

  1. Organization of Response Areas in Ferret Primary Auditory Cortex

    National Research Council Canada - National Science Library

    Shamma, S. A; Fleshman, J. W; Wiser, P. R; Versnel, H

    1992-01-01

    ...) in the barbiturate- auesthetized ferret. Using a two-tone stimulus, the excitatory and inhibitory portious of the response areas were determined and then parametrized in terms of an asymmetry index...

  2. The draft genome sequence of the ferret (Mustela putorius furo) facilitates study of human respiratory disease.

    Science.gov (United States)

    Peng, Xinxia; Alföldi, Jessica; Gori, Kevin; Eisfeld, Amie J; Tyler, Scott R; Tisoncik-Go, Jennifer; Brawand, David; Law, G Lynn; Skunca, Nives; Hatta, Masato; Gasper, David J; Kelly, Sara M; Chang, Jean; Thomas, Matthew J; Johnson, Jeremy; Berlin, Aaron M; Lara, Marcia; Russell, Pamela; Swofford, Ross; Turner-Maier, Jason; Young, Sarah; Hourlier, Thibaut; Aken, Bronwen; Searle, Steve; Sun, Xingshen; Yi, Yaling; Suresh, M; Tumpey, Terrence M; Siepel, Adam; Wisely, Samantha M; Dessimoz, Christophe; Kawaoka, Yoshihiro; Birren, Bruce W; Lindblad-Toh, Kerstin; Di Palma, Federica; Engelhardt, John F; Palermo, Robert E; Katze, Michael G

    2014-12-01

    The domestic ferret (Mustela putorius furo) is an important animal model for multiple human respiratory diseases. It is considered the 'gold standard' for modeling human influenza virus infection and transmission. Here we describe the 2.41 Gb draft genome assembly of the domestic ferret, constituting 2.28 Gb of sequence plus gaps. We annotated 19,910 protein-coding genes on this assembly using RNA-seq data from 21 ferret tissues. We characterized the ferret host response to two influenza virus infections by RNA-seq analysis of 42 ferret samples from influenza time-course data and showed distinct signatures in ferret trachea and lung tissues specific to 1918 or 2009 human pandemic influenza virus infections. Using microarray data from 16 ferret samples reflecting cystic fibrosis disease progression, we showed that transcriptional changes in the CFTR-knockout ferret lung reflect pathways of early disease that cannot be readily studied in human infants with cystic fibrosis disease.

  3. Tetralogy of Fallot in a 6-year-old albino ferret (Mustela putorius furo)

    Science.gov (United States)

    Laniesse, Delphine; Hébert, Julie; Larrat, Sylvain; Hélie, Pierre; Pouleur-Larrat, Bénédicte; Belanger, Marie C.

    2014-01-01

    Tetralogy of Fallot associated with bidirectional shunting across a large ventricular septal defect, was found in a 6-year-old ferret. The prognosis associated with tetralogy of Fallot is usually poor. This case is interesting given the advanced age of the ferret. The bidirectional shunting, responsible for an acyanotic disease, may explain the unexpected prolonged survival in this ferret. PMID:24790231

  4. Feral ferrets (Mustela furo) as hosts and sentinels of tuberculosis in New Zealand

    Science.gov (United States)

    Byrom, AE; Caley, P; Paterson, BM; Nugent, G

    2015-01-01

    Abstract The control and eventual eradication of bovine tuberculosis (TB) poses major challenges in New Zealand, given the variety of wildlife species susceptible to TB, many of which are capable of onwards transmission of Mycobacterium bovis infection. Here we discuss the role of feral ferrets (Mustela furo), focussing on potential transmission or risk pathways that have implications for management of TB. Firstly inter-specific transmission to ferrets. Ferrets scavenge potentially infected wildlife, including other ferrets, thus prevalence of TB can be amplified through ferrets feeding on tuberculous carcasses, particularly brushtail possums (Trichosurus vulpecula). Secondly intra-specific transmission between ferrets. The rate of ferret-ferret transmission depends on population density, and in some places ferret densities exceed the estimated threshold for disease persistence. TB can therefore potentially be maintained independently of other sources of infection. Thirdly transmission from ferrets to other wildlife. These include the main wildlife maintenance host, brushtail possums, that will occasionally scavenge potentially tuberculous ferret carcasses. Fourthly transmission from ferrets to livestock. This is considered to occur occasionally, but the actual rate of transmission has never been measured. Fifthly geographical spread. M. bovis-infected ferrets can travel large distances and cause new outbreaks of TB at locations previously free of TB, which may have caused an expansion of TB-endemic areas.Ferrets play a complex role in the TB cycle in New Zealand; they are capable of contracting, amplifying and transmitting M. bovis infection, sometimes resulting in ferret populations with a high prevalence of TB. However, ferret population densities are usually too low to sustain infection independently, and transmission to other wildlife or livestock appears a rarer event than with possums. Nevertheless, management of ferrets remains a key part of the National

  5. Cytokine release from human peripheral blood leucocytes incubated with endotoxin with and without prior infection with influenza virus

    DEFF Research Database (Denmark)

    Banner, Jytte; Smith, H; Sweet, C

    1993-01-01

    Previous work with a neonatal ferret model for human SIDS had indicated that inflammation caused by a combination of influenza virus and bacterial endotoxin may be a cause of human SIDS. To determine whether cytokines may be involved in this inflammatory response, levels of interleukin (IL)-1 beta...

  6. Nitric oxide synthase in ferret brain: localization and characterization.

    Science.gov (United States)

    Matsumoto, T.; Mitchell, J. A.; Schmidt, H. H.; Kohlhaas, K. L.; Warner, T. D.; Förstermann, U.; Murad, F.

    1992-01-01

    1. In the present study, we have investigated the distribution of nitric oxide synthase in the ferret brain. Nitric oxide synthase was determined biochemically and immunochemically. 2. In the rat brain, the highest nitric oxide synthase activity has been detected in the cerebellum. However, in the ferret brain, the highest activity was found in the striatum and the lowest in the cerebellum and cerebral cortex. The enzymatic activity was localized predominantly in the cytosolic fractions, it was dependent on NADPH and Ca2+, and inhibited by NG-nitro-L-arginine or NG-methyl-L-arginine. 3. Western blot analysis revealed that all regions of the ferret brain contained a 160 kD protein crossreacting with an antibody to nitric oxide synthase purified from the rat cerebellum, and the levels of relative intensity of staining by the antibody correlated with the distribution of nitric oxide synthase activity. 4. These results indicate that the ferret brain contains a nitric oxide synthase similar to the rat brain, but the distribution of enzymatic activity in the ferret brain differs markedly from the rat brain. Images Figure 1 PMID:1282076

  7. Hemagglutinin Stalk Immunity Reduces Influenza Virus Replication and Transmission in Ferrets.

    Science.gov (United States)

    Nachbagauer, Raffael; Miller, Matthew S; Hai, Rong; Ryder, Alex B; Rose, John K; Palese, Peter; García-Sastre, Adolfo; Krammer, Florian; Albrecht, Randy A

    2015-12-30

    We assessed whether influenza virus hemagglutinin stalk-based immunity protects ferrets against aerosol-transmitted H1N1 influenza virus infection. Immunization of ferrets by a universal influenza virus vaccine strategy based on viral vectors expressing chimeric hemagglutinin constructs induced stalk-specific antibody responses. Stalk-immunized ferrets were cohoused with H1N1-infected ferrets under conditions that permitted virus transmission. Hemagglutinin stalk-immunized ferrets had lower viral titers and delayed or no virus replication at all following natural exposure to influenza virus. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  8. Somatic immunoglobulin hypermutation

    OpenAIRE

    Diaz, Marilyn; Casali, Paolo

    2002-01-01

    Immunoglobulin hypermutation provides the structural correlate for the affinity maturation of the antibody response. Characteristic modalities of this mechanism include a preponderance of point-mutations with prevalence of transitions over transversions, and the mutational hotspot RGYW sequence. Recent evidence suggests a mechanism whereby DNA-breaks induce error-prone DNA synthesis in immunoglobulin V(D)J regions by error-prone DNA polymerases. The nature of the targeting mechanism and the t...

  9. Equine immunoglobulins and organization of immunoglobulin genes.

    Science.gov (United States)

    Walther, Stefanie; Rusitzka, Tamara V; Diesterbeck, Ulrike S; Czerny, Claus-Peter

    2015-12-01

    Our understanding of how equine immunoglobulin genes are organized has increased significantly in recent years. For equine heavy chains, 52 IGHV, 40 IGHD, 8 IGHJ and 11 IGHC are present. Seven of these IGHCs are gamma chain genes. Sequence diversity is increasing between fetal, neonatal, foal and adult age. The kappa light chain contains 60 IGKV, 5 IGKJ and 1 IGKC, whereas there are 144 IGLV, 7 IGLJ, and 7 IGLC for the lambda light chain, which is expressed predominantly in horses. Significant transcriptional differences for IGLV and IGLC are identified in different breeds. Allotypic and allelic variants are observed for IGLC1, IGLC5, and IGLC6/7, and two IGLV pseudogenes are also transcribed. During age development, a decrease in IGLVs is noted, although nucleotide diversity and significant differences in gene usage increased. The following paper suggests a standardization of the existing nomenclature of immunoglobulin genes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Bilateral perinephric pseudocysts and polycystic kidneys in a ferret

    International Nuclear Information System (INIS)

    Puerto, D.A.; Walker, L.M.; Saunders, H.M.

    1998-01-01

    A 3-year-old castrated male domestic ferret was evaluated for abdominal distention. Survey lateral and dorsoventral abdominal radiographs were made. There were two soft tissue radiopacities consistent with grossly enlarged kidneys displacing small bowel and colon cranially, ventrally and caudally. Abdominal ultrasound was performed and revealed bilateral perinephric pseudocysts and polycystic kidneys. The perinephric pseudocysts were found to be dilated renal capsules on exploratory surgery and were drained. On follow up examinations, the pseudocysts were drained by ultrasound-guided paracentesis. The perinephric cyst fluid was distinguished from urine by measuring creatinine concentration and plans were made to resect the renal capsules due to rapid re-accumulation of pseudocyst fluid. The ferret's condition deteriorated and euthanasia was performed. Post-mortem examination was declined by the owner. Perinephric pseudocysts are rare and this is the first published report in a ferret. Ultrasound examination is the most rapid, accurate and non-invasive method for diagnosis of perinephric pseudocysts

  11. Resource selection by black-footed ferrets in South Dakota and Montana

    Science.gov (United States)

    Jachowski, D.S.; Millspaugh, J.J.; Biggins, D.E.; Livieri, T.M.; Matchett, M.R.; Rittenhouse, C.D.

    2011-01-01

    The black-footed ferret (Mustela nigripes), once extinct in the wild, remains one of the most critically endangered mammals in North America despite 18 years of reintroduction attempts. Because black-footed ferrets are specialized predators of prairie dogs (Cynomys sp.), a better understanding of how black-footed ferrets select resources might provide insight into how best to identify and manage reintroduction sites. We monitored ferret resource selection at two reintroduction sites with different densities of prairie dog populations-one that contained a high density of prairie dogs (Conata Basin, South Dakota) and one that was lower (UL Bend, Montana). We evaluated support for hypotheses about ferret resource selection as related to the distribution of active burrows used by black-tailed prairie dogs (Cynomys ludovicianus), interactions between ferrets, and habitat edge effects. We found support for all three factors within both populations; however, they affected ferret resource selection differently at each site. Ferrets at Conata Basin tended to select areas with high prairie dog burrow density, closer to the colony edge, and that overlapped other ferret ranges. In contrast, ferrets at UL Bend tended not to select areas of high active prairie dog burrow density, avoided areas close to edge habitat, and females avoided areas occupied by other ferrets. The differences observed between the two sites might be best explained by prairie dog densities, which were higher at Conata Basin (119.3 active burrows per ha) than at UL Bend (44.4 active burrows per ha). Given the positive growth of ferret populations at Conata Basin, management that increases the density of prairie dogs might enhance ferret success within natural areas. To achieve long-term recovery of ferrets in the wild, conservationists should increasingly work across and outside natural area boundaries to increase prairie dog populations.

  12. Characterization of immunoglobulin G fragments in liquid intravenous immunoglobulin products

    NARCIS (Netherlands)

    Diemel, Robert V.; ter Hart, Hendricus G. J.; Derksen, Gerardus J. A.; Koenderman, Anky H. L.; Aalberse, Rob C.

    2005-01-01

    Intravenous immunoglobulin (IVIG) products formulated as a liquid instead of a powder have become commercially available. Preferably, such liquid products should not alter after storage outside the refrigerator. Therefore, a thorough characterization of immunoglobulin G (IgG) fragmentation at

  13. Oral Malignant Melanoma in a Ferret ( Mustela putorius furo).

    Science.gov (United States)

    d'Ovidio, Dario; Rossi, Giacomo; Meomartino, Leonardo

    2016-06-01

    Oral malignant melanomas are one of the most common oral malignant neoplasms in dogs but are rare in other domesticated species. This case report describes the clinical manifestations and histological appearance of oral melanoma in a ferret ( Mustela putorius furo). To the authors' knowledge, this is the first published description of a clinical case and histopathological findings of oral melanoma in this species.

  14. Carpal myxosarcoma and forelimb amputation in a ferret

    NARCIS (Netherlands)

    van Zeeland, Y.R.A.; Hernandez-Divers, S.J.; Blasier, M.W.; Vila-Garcia, G.; Delong, D.; Stedman, N.L.

    2006-01-01

    Vet Rec. 2006 Dec 2;159(23):782-5. Carpal myxosarcoma and forelimb amputation in a ferret (Mustela putorius furo). van Zeeland YR, Hernandez-Divers SJ, Blasier MW, Vila-Garcia G, Delong D, Stedman NL. Department of Small Animal Medicine, Faculty of Veterinary Medicine, University of Utrecht,

  15. Refinement of the Care and Use of Laboratory Ferrets

    NARCIS (Netherlands)

    Reijgwart, Marsinah Lusanne

    2017-01-01

    Ferrets (Mustela putorius furo) are a valuable animal model in biomedical research, e.g. for studying human diseases such as influenza. Legislation requires studies using animals to adhere to the principle of the 3Rs, i.e. to replace the use of animals where possible; to reduce the number of animals

  16. Black-footed ferrets and Siberian polecats as ecological surrogates and ecological equivalents

    Science.gov (United States)

    Biggins, D.E.; Hanebury, L.R.; Miller, B.J.; Powell, R.A.

    2011-01-01

    Ecologically equivalent species serve similar functions in different communities, and an ecological surrogate species can be used as a substitute for an equivalent species in a community. Siberian polecats (Mustela eversmanii) and black-footed ferrets (M. nigripes) have long been considered ecological equivalents. Polecats also have been used as investigational surrogates for black-footed ferrets, yet the similarities and differences between the 2 species are poorly understood. We contrasted activity patterns of radiotagged polecats and ferrets released onto ferret habitat. Ferrets tended to be nocturnal and most active after midnight. Polecats were not highly selective for any period of the day or night. Ferrets and polecats moved most during brightly moonlit nights. The diel activity pattern of ferrets was consistent with avoidance of coyotes (Canis latrans) and diurnal birds of prey. Similarly, polecat activity was consistent with avoidance of red foxes (Vulpes vulpes) in their natural range. Intraguild predation (including interference competition) is inferred as a selective force influencing behaviors of these mustelines. Examination of our data suggests that black-footed ferrets and Siberian polecats might be ecological equivalents but are not perfect surrogates. Nonetheless, polecats as surrogates for black-footed ferrets have provided critical insight needed, especially related to predation, to improve the success of ferret reintroductions. ?? 2011 American Society of Mammalogists.

  17. Landscape features influence postrelease predation on endangered black-footed ferrets

    Science.gov (United States)

    Poessel, S.A.; Breck, S.W.; Biggins, D.E.; Livieri, T.M.; Crooks, K.R.; Angeloni, L.

    2011-01-01

    Predation can be a critical factor influencing recovery of endangered species. In most recovery efforts lethal and nonlethal influences of predators are not sufficiently understood to allow prediction of predation risk, despite its importance. We investigated whether landscape features could be used to model predation risk from coyotes (Canis latrans) and great horned owls (Bubo virginianus) on the endangered black-footed ferret (Mustela nigripes). We used location data of reintroduced ferrets from 3 sites in South Dakota to determine whether exposure to landscape features typically associated with predators affected survival of ferrets, and whether ferrets considered predation risk when choosing habitat near perches potentially used by owls or near linear features predicted to be used by coyotes. Exposure to areas near likely owl perches reduced ferret survival, but landscape features potentially associated with coyote movements had no appreciable effect on survival. Ferrets were located within 90 m of perches more than expected in 2 study sites that also had higher ferret mortality due to owl predation. Densities of potential coyote travel routes near ferret locations were no different than expected in all 3 sites. Repatriated ferrets might have selected resources based on factors other than predator avoidance. Considering an easily quantified landscape feature (i.e., owl perches) can enhance success of reintroduction efforts for ferrets. Nonetheless, development of predictive models of predation risk and management strategies to mitigate that risk is not necessarily straightforward for more generalist predators such as coyotes. ?? 2011 American Society of Mammalogists.

  18. FLEAS OF BLACK-FOOTED FERRETS (MUSTELA NIGRIPES) AND THEIR POTENTIAL ROLE IN THE MOVEMENT OF PLAGUE.

    Science.gov (United States)

    Mize, Erica L; Grassel, Shaun M; Britten, Hugh B

    2017-07-01

    Sylvatic plague is one of the major impediments to the recovery of the black-footed ferret ( Mustela nigripes ) because it decimates their primary prey species, prairie dogs ( Cynomys spp.), and directly causes mortality in ferrets. Fleas are the primary vector of Yersinia pestis , the causative agent of sylvatic plague. The goal of this research was to better understand the flea fauna of ferrets and the factors that might influence flea abundance on ferrets. Fleas from ferrets were tested for Y. pestis in a post hoc assessment to investigate the plausibility that some ferrets could act as incidental transporter hosts of fleas infected with Y. pestis . Fleas were collected from ferrets captured on the Lower Brule Indian Reservation in central South Dakota, US from 2009 to 2012. A total of 528 fleas collected from 67 individual ferrets were identified and tested for the presence of Y. pestis with a nested PCR assay. The predominant flea recovered from ferrets was Oropsylla hirsuta , a species that comprises 70-100% of the fleas recovered from prairie dogs and their burrows in the study area. Yersinia pestis was detected at low levels in fleas collected from ferrets with prevalence ranging from 0% to 2.9%; male ferrets harbored significantly more fleas than female ferrets. Six of 67 ferrets vaccinated against plague carried fleas that tested positive for Y. pestis , which suggests ferrets vaccinated against plague could inadvertently act as incidental transporter hosts of Y. pestis -positive fleas.

  19. Immunoglobulins for preventing hepatitis A

    DEFF Research Database (Denmark)

    Liu, Jian Ping; Nikolova, Dimitrinka; Fei, Yutong

    2009-01-01

    Hepatitis A (infectious hepatitis) is a common epidemic disease. Immunoglobulins for passive immunisation are used as prevention.......Hepatitis A (infectious hepatitis) is a common epidemic disease. Immunoglobulins for passive immunisation are used as prevention....

  20. Immunoglobulin and fatty acids

    DEFF Research Database (Denmark)

    2009-01-01

    The present invention relates to a composition comprising 0.1-10 w/w % immunoglobulin (Ig), 4-14 w/w % saturated fatty acids, 4-14 w/w % mono-unsaturated fatty acids and 0-5 w/w % poly-unsaturated fatty acids, wherein the weight percentages are based on the content of dry matter in the composition...

  1. Inefficient Transmission of H5N1 Influenza Viruses in a Ferret Contact Model▿

    OpenAIRE

    Yen, Hui-Ling; Lipatov, Aleksandr S.; Ilyushina, Natalia A.; Govorkova, Elena A.; Franks, John; Yilmaz, Neziha; Douglas, Alan; Hay, Alan; Krauss, Scott; Rehg, Jerold E.; Hoffmann, Erich; Webster, Robert G.

    2007-01-01

    The abilities to infect and transmit efficiently among humans are essential for a novel influenza A virus to cause a pandemic. To evaluate the pandemic potential of widely disseminated H5N1 influenza viruses, a ferret contact model using experimental groups comprised of one inoculated ferret and two contact ferrets was used to study the transmissibility of four human H5N1 viruses isolated from 2003 to 2006. The effects of viral pathogenicity and receptor binding specificity (affinity to synth...

  2. Movements and survival of black-footed ferrets associated with an experimental translocation in South Dakota

    Science.gov (United States)

    Biggins, D.E.; Godbey, J.L.; Horton, B.M.; Livieri, T.M.

    2011-01-01

    Black-footed ferrets (Mustela nigripes) apparently were extirpated from all native habitats by 1987, and their repatriation requires a combination of captive breeding, reintroductions, and translocations among sites. Improvements in survival rates of released ferrets have resulted from experience in quasi-natural environments during their rearing. Reestablishment of a self-sustaining wild population by 1999 provided the 1st opportunity to initiate new populations by translocating wild-born individuals. Using radiotelemetry, we compared behaviors and survival of 18 translocated wild-born ferrets and 18 pen-experienced captive-born ferrets after their release into a prairie dog colony not occupied previously by ferrets. Translocated wild-born ferrets moved significantly less and had significantly higher short-term survival rates than their captive-born counterparts. Using markrecapture methods, we also assessed potential impacts to the established donor population of removing 37% of its estimated annual production of kits. Annual survival rates for 30 ferret kits remaining at the donor subcomplex were higher than rates for 54 ferret kits at the control subcomplex (unmanipulated) for males (+82%) and females (+32%). Minimum survival of translocated kits did not differ significantly from survival of those at the control subcomplex. Direct translocation of young, wild-born ferrets from site to site appears to be an efficient method to establish new populations. ?? 2011 American Society of Mammalogists.

  3. [Selective immunoglobulin A deficiency].

    Science.gov (United States)

    Binek, Alicja; Jarosz-Chobot, Przemysława

    2012-01-01

    Immunoglobulin class A is the main protein of the mucosal immune system. Selective immunoglobulin A deficiency (sIgAD) is the most common primary immunodeficiency in Caucasians. sIGAD is strongly associated with the certain major histocompatibility complex region. Most individuals with sIgAD are asymptomatic and identified coincidentally. However, some patients may present with recurrent infections, allergic disorders and autoimmune manifestations. Several autoimmune diseases, such as systemic lupus erythematosus, diabetes mellitus type 1, Graves disease and celiac disease, are associated with an increased prevalence of sIgAD. Screening for sIgAD in coeliac disease is essential. Patients need treatment of associated diseases. It is also known that IgA deficiency may progress into a common variable immunodeficiency (CVID). Pathogenesis and molecular mechanism involved in sIgAD should be elucidated in the future.

  4. The ferret as a model for inner ear research.

    Science.gov (United States)

    Rarey, K E

    1985-06-01

    Viral infections have long been suspected to be causative agents in a number of inner ear dysfunctions. With few exceptions, the virus has not been demonstrated as the direct agent leading to hearing loss and/or vertigo. Selective inner ear changes have been observed recently in sensory and nonsensory epithelial cells in the ferret model for Reye's syndrome after intranasal inoculation with influenza B combined with aspirin administration and the creation of an arginine deficiency. Such findings suggest that these agents act synergistically on the inner ear, particularly on cells that are metabolically active, and that the ferret may now be a useful model to examine the role of certain upper respiratory tract viruses implicated in inner ear disorders, singly and in combination with other agents that may cause metabolic alterations.

  5. Immunoglobulin genes of the turtles.

    Science.gov (United States)

    Magadán-Mompó, Susana; Sánchez-Espinel, Christian; Gambón-Deza, Francisco

    2013-03-01

    The availability of reptile genomes for the use of the scientific community is an exceptional opportunity to study the evolution of immunoglobulin genes. The genome of Chrysemys picta bellii and Pelodiscus sinensis is the first one that has been reported for turtles. The scanning for immunoglobulin genes resulted in the presence of a complex locus for the immunoglobulin heavy chain (IGH). This IGH locus in both turtles contains genes for 13 isotypes in C. picta bellii and 17 in P. sinensis. These correspond with one immunoglobulin M, one immunoglobulin D, several immunoglobulins Y (six in C. picta bellii and eight in P. sinensis), and several immunoglobulins that are similar to immunoglobulin D2 (five in C. picta belli and seven in P. sinensis) that was previously described in Eublepharis macularius. It is worthy to note that IGHD2 are placed in an inverted transcriptional orientation and present sequences for two immunoglobulin domains that are similar to bird IgA domains. Furthermore, its phylogenetic analysis allows us to consider about the presence of IGHA gene in a primitive reptile, so we would be dealing with the memory of the gene that originated from the bird IGHA. In summary, we provide a clear picture of the immunoglobulins present in a turtle, whose analysis supports the idea that turtles emerged from the evolutionary line from the differentiation of birds and the presence of the IGHA gene present in a common ancestor.

  6. Postbreeding resource selection by adult black-footed ferrets in the Conata Basin, South Dakota

    Science.gov (United States)

    Eads, D.A.; Millspaugh, J.J.; Biggins, D.E.; Livieri, T.M.; Jachowski, D.S.

    2011-01-01

    We investigated postbreeding resource selection by adult black-footed ferrets (Mustela nigripes) on a 452-ha black-tailed prairie dog (Cynomys ludovicianus) colony in the Conata Basin of South Dakota during 20072008. We used resource selection functions (RSFs) to evaluate relationships between numbers of ferret locations and numbers of prairie dog burrow openings (total or active), distances to colony edges, and connectivity of patches of burrow openings. In both years ferrets selected areas near edges of the prairie dog colony where active burrow openings were abundant. In the interior of the colony ferrets selected areas with low abundance of active burrow openings. At times, prairie dog productivity (i.e., pup abundance) might be greatest at colony edges often characterized by grasses; ferrets are likely to select areas where refuge and vulnerable prey are abundant. Ferrets could have used interior areas with few active burrow openings as corridors between edge areas with many active burrow openings. Also, in areas with few active burrow openings ferrets spend more time aboveground during movements and, thus, are likely to be more easily detected. These results complement previous studies demonstrating importance of refuge and prey in fine-scale resource selection by ferrets and provide insight into factors that might influence edge effects on ferret space use. Conservation and restoration of colonies with areas with high densities of burrow openings and prairie dogs, and corridors between such areas, are needed for continued recovery of the black-footed ferret. RSFs could complement coarse-scale habitat evaluations by providing finer-scale assessments of habitat for the black-footed ferret. ?? 2011 American Society of Mammalogists.

  7. Radiographic measurement of cardiac size in 64 ferrets

    International Nuclear Information System (INIS)

    Onuma, M.; Kondo, H.; Ono, S.; Ueki, M.; Shibuya, H.; Sato, T.

    2009-01-01

    As ferrets can suffer from a wide variety of cardiac disorders, indicators for detecting cardiac abnormalities on plain chest radiography are necessary. A total of 64 ferrets without heart disease underwent radiography in the right lateral (RL) and ventrodorsal positions (VD), and the lengths of the RL-sixth dorsal vertebra (6th DV), RL- and VD-long axis (LA) and RL- and VD-short axis (SA), RL- and VD-vertebral heart size, VD-length of the eighth costa (LEC) and VD-thoracic width at the eighth thoracic vertebra (8th TV) were measured to establish standard values of normal cardiac appearance. We evaluated statistical differences between genders and ferrets weighing 1 kg and = 1 kg for a total of 38 items. As a result, significant differences (P0.05) were observed in all items, including some differences that have been reported previously. In particular, the present study established highly accurate standard values for weight differences. Standard values calculated based on the 6th DV and a relational expression obtained by the regression coefficient of the ratio of VD-SA to VD-8th TV, VD-8th TV

  8. Fine-scale habitat use of reintroduced black-footed ferrets on prairie dog colonies in New Mexico

    Science.gov (United States)

    Chipault, Jennifer G.; Biggins, Dean E.; Detling, James K.; Long, Dustin H.; Reich, Robin M.

    2012-01-01

    Black-footed ferrets (Mustela nigripes) are among the most endangered animals in North America. Reintroductions of captive-born ferrets onto prairie dog (Cynomys spp.) colonies are crucial to the conservation of the species. In September 2007, captive-born ferrets were released on a black-tailed prairie dog (Cynomys ludovicianus) colony at the Vermejo Park Ranch, New Mexico. Ferret kits experimentally released in areas of comparatively low and high prairie dog burrow densities were located via spotlight surveys. Some maturing ferret kits were subsequently translocated to areas of low and high burrow densities on nearby prairie dog colonies. For 2 months, fine-scale habitat use was quantified by mapping all burrow openings within a 30-m radius of each ferret location. Spatial statistics accounted for autocorrelation in the burrow densities in areas used by ferrets. It was hypothesized that ferrets would select areas of high burrow densities within colonies; however, burrow densities in areas used by ferrets were generally similar to the available burrow densities. Because ferrets used areas with burrow densities similar to densities available at the colony level and because of the potential energetic benefits for ferrets using areas with high burrow densities, releasing ferrets on colonies with high burrow densities might increase reintroduction success.

  9. Rhinitis and disseminated disease in a ferret (Mustela putorius futo) naturally infected with Sarcocystis neurona

    Science.gov (United States)

    Naturally occurring Sarcocystis neurona infection in a ferret (Mustela putorius futo) with rhinitis and disseminated disease are described for the first time. The ferret exhibited severe rhinitis with intra-lesional S. neurona merozoites and schizonts. Diagnosis was confirmed immunohistochemically b...

  10. Non-invasive blood pressure measurement in ferrets (Mustela putorius furo) using high definition oscillometry

    NARCIS (Netherlands)

    van Zeeland, Y. R.A.; Wilde, A.; Bosman, I.H.; Uilenreef, J. J.; Egner, B.I.; Schoemaker, N. J.

    2017-01-01

    This study was conducted to validate the use of high definition oscillometry (HDO) for non-invasive blood pressure (NIBP) measurements in ferrets and to establish reference ranges for NIBP in minimally sedated, healthy, young adult ferrets (170 mmHg) conditions. Although HDO correlated well with

  11. Fatal vaccine-induced canine distemper virus infection in black-footed ferrets

    Science.gov (United States)

    Carpenter, J.W.; Appel, M.J.G.; Erickson, R.C.; Novilla, M.N.

    1976-01-01

    Four black-footed ferrets that were live-trapped in South Dakota and transported to the Patuxent Wildlife Research Center died within 21 days after vaccination with modified live canine distemper virus. Immunofluorescence, European ferret inoculation, virus isolation attempts, and serum-neutralization tests indicated insufficient attenuation of the vaccine for this species.

  12. A case of advanced second-degree atrioventricular block in a ferret ...

    African Journals Online (AJOL)

    A case of advanced second-degree atrioventricular block in a ferret secondary to lymphoma. ... A female ferret was referred as an emergency for severe respiratory distress symptoms. ... Moreover, a pericardial lymphocytic infiltration and a widespread myocardial nodular localization of lymphoma were evidenced as well.

  13. Morning ambush attacks by black-footed ferrets on emerging prairie dogs

    Science.gov (United States)

    Eads, D.A.; Biggins, D.E.; Jachowski, D.S.; Livieri, T.M.; Millspaugh, J.J.; Forsberg, M.

    2010-01-01

    Black-footed ferrets (Mustela nigripes) often hunt at night, attacking normally diurnal prairie dogs (Cynomys spp.) in underground burrow systems. While monitoring black-footed ferrets in South Dakota during morning daylight hours, we observed an adult female ferret ambush a black-tailed prairie dog (C. ludovicianus) emerging from a burrow. On a neighboring colony, we observed a second adult female ferret engaging in similar ambush behaviors on 12 occasions, although prey was not visible. We retrospectively assessed radio-telemetry data on white-tailed prairie dogs (C. leucurus) and a male and a female ferret to evaluate ferret activity in relation to timing of prairie dog emergence. Activity of radio-collared ferrets was high during the hourly period when prairie dogs first emerged and the following 2 hr, relative to later daylight hours. Such behavior is consistent with behaviors observed in South Dakota. Nighttime movements by ferrets might involve hunting but also reconnaissance of prey preparatory to morning ambush attacks.

  14. Use of multi-opening burrow systems by black-footed ferrets

    Science.gov (United States)

    Biggins, Dean E.

    2012-01-01

    Multi-opening burrow systems constructed by prairie dogs (Cynomys) ostensibly provide escape routes when prairie dogs are pursued by predators capable of entering the burrows, such as black-footed ferrets (Mustela nigripes), or by predators that can rapidly dig into the tunnels, such as American badgers (Taxidea taxus). Because badgers also prey on ferrets, ferrets might similarly benefit from multi-opening burrow systems. Using an air blower, white-tailed prairie dog (Cynomys leucurus) burrow openings were tested for connectivity on plots occupied by black-footed ferrets and on randomly selected plots in Wyoming. Significantly more connected openings were found on ferret-occupied plots than on random plots. Connected openings might be due to modifications by ferrets in response to plugging by prairie dogs, due to selection by ferrets for complex systems with multiple openings that are already unobstructed, or simply due to ferrets lingering at kill sites that were multi-opening systems selected by their prairie dog prey.

  15. Transcriptome sequencing and development of an expression microarray platform for the domestic ferret

    Directory of Open Access Journals (Sweden)

    McBrayer Alexis

    2010-04-01

    Full Text Available Abstract Background The ferret (Mustela putorius furo represents an attractive animal model for the study of respiratory diseases, including influenza. Despite its importance for biomedical research, the number of reagents for molecular and immunological analysis is restricted. We present here a parallel sequencing effort to produce an extensive EST (expressed sequence tags dataset derived from a normalized ferret cDNA library made from mRNA from ferret blood, liver, lung, spleen and brain. Results We produced more than 500000 sequence reads that were assembled into 16000 partial ferret genes. These genes were combined with the available ferret sequences in the GenBank to develop a ferret specific microarray platform. Using this array, we detected tissue specific expression patterns which were confirmed by quantitative real time PCR assays. We also present a set of 41 ferret genes with even transcription profiles across the tested tissues, indicating their usefulness as housekeeping genes. Conclusion The tools developed in this study allow for functional genomic analysis and make further development of reagents for the ferret model possible.

  16. Issues to consider for preparing ferrets as research subjects in the laboratory.

    Science.gov (United States)

    Ball, Roberta Scipioni

    2006-01-01

    The domestic or European ferret (Mustela putorius furo) has been domesticated for thousands of years. Ferrets have been used for hunting and fur production, as pets, and as models in biomedical research. Despite the relatively small numbers used in the laboratory, ferrets have some unique applications including study of human influenza and severe acute respiratory syndrome (SARS)-associated corona virus. They have served as models for peptic ulcer disease, carotenoid metabolism, cystic fibrosis, and drug emesis screening, among others. Most research ferrets are males, due to estrus-related health problems in females. They may be housed conventionally and are easy to care for when their biology and behavior are understood. Due to the small number of ferret suppliers, animals are often shipped long distances, requiring air transport and intermediate handlers. It is important to minimize shipment stress, especially with weanling and pregnant animals. Additional expertise is required for success with pregnant and whelping ferrets and for rearing of neonates. The animals have specific dietary requirements, and proper nutrition is key. Successful housing requires knowledge of ferret behaviors including social behavior, eating habits, a general inquisitive nature, and a species-typical need to burrow and hide. Regular handling is necessary to maintain well-being. A ferret health care program consists of physical examination, immunization, clinical pathology, and a working knowledge of common ferret diseases. Various research methodologies have been described, from basic procedures such as blood collection to major invasive survival surgery. Ferrets have a distinct niche in biomedical research and are hardy animals that thrive well in the laboratory.

  17. American badgers selectively excavate burrows in areas used by black-footed ferrets: implications for predator avoidance

    Science.gov (United States)

    Eads, David A.; Biggins, Dean E.; Livieri, Travis M.; Millspaugh, Joshua J.

    2013-01-01

    We evaluated how American badgers (Taxidea taxus) might exert selective pressure on black-footed ferrets (Mustela nigripes) to develop antipredator defenses. In a colony of black-tailed prairie dogs (Cynomys ludovicianus) in South Dakota, badgers concentrated their activities where burrow openings and prairie dogs were abundant, a selective behavior that was exhibited by ferrets in the same colony. Badgers excavated burrows more often when in areas recently used by a ferret, suggesting that badgers hunt ferrets or steal prey from ferrets, or both. We also conducted an analysis of survival studies for ferrets and Siberian polecats (M. eversmanii) released onto prairie dog colonies. This polecat is the ferret's ecological equivalent but evolved without a digging predator. Badgers accounted for 30.0% of predation on polecats and 5.5% of predation on ferrets. In contrast, both polecats and ferrets have evolutionary experience with canids, providing a plausible explanation for the similar relative impact of coyotes (Canis latrans) on them (65.0% and 67.1% of predation, respectively). We hypothesize that ferrets and badgers coexist because ferrets are superior at exploitation competition and are efficient at avoiding badgers, and badgers are superior at interference competition.

  18. Patterns of surface burrow plugging in a colony of black-tailed prairie dogs occupied by black-footed ferrets

    Science.gov (United States)

    Eads, David E.; Biggins, Dean E.

    2012-01-01

    Black-tailed prairie dogs (Cynomys ludovicianus) can surface-plug openings to a burrow occupied by a black-footed ferret (Mustela nigripes). At a coarse scale, surface plugs are more common in colonies of prairie dogs occupied by ferrets than in colonies without ferrets. However, little is known about spatial and temporal patterns of surface plugging in a colony occupied by ferrets. In a 452-ha colony of black-tailed prairie dogs in South Dakota, we sampled burrow openings for surface plugs and related those data to locations of ferrets observed during spotlight surveys. Of 67,574 burrow openings in the colony between June and September 2007, 3.7% were plugged. In a colony-wide grid of 80 m × 80 m cells, the occurrence of surface plugging (≥1 opening plugged) was greater in cells used by ferrets (93.3% of cells) than in cells not observably used by ferrets (70.6%). Rates of surface plugging (percentages of openings plugged) were significantly higher in cells used by ferrets (median = 3.7%) than in cells without known ferret use (median = 3.2%). Also, numbers of ferret locations in cells correlated positively with numbers of mapped surface plugs in the cells. To investigate surface plugging at finer temporal and spatial scales, we compared rates of surface plugging in 20-m-radius circle-plots centered on ferret locations and in random plots 1–4 days after observing a ferret (Jun–Oct 2007 and 2008). Rates of surface plugging were greater in ferret-plots (median = 12.0%) than in random plots (median = 0%). For prairie dogs and their associates, the implications of surface plugging could be numerous. For instance, ferrets must dig to exit or enter plugged burrows (suggesting energetic costs), and surface plugs might influence microclimates in burrows and consequently influence species that cannot excavate soil (e.g., fleas that transmit the plague bacterium Yersinia pestis).

  19. Ferret: a sentence-based literature scanning system.

    Science.gov (United States)

    Srinivasan, Padmini; Zhang, Xiao-Ning; Bouten, Roxane; Chang, Caren

    2015-06-20

    The rapid pace of bioscience research makes it very challenging to track relevant articles in one's area of interest. MEDLINE, a primary source for biomedical literature, offers access to more than 20 million citations with three-quarters of a million new ones added each year. Thus it is not surprising to see active research in building new document retrieval and sentence retrieval systems. We present Ferret, a prototype retrieval system, designed to retrieve and rank sentences (and their documents) conveying gene-centric relationships of interest to a scientist. The prototype has several features. For example, it is designed to handle gene name ambiguity and perform query expansion. Inputs can be a list of genes with an optional list of keywords. Sentences are retrieved across species but the species discussed in the records are identified. Results are presented in the form of a heat map and sentences corresponding to specific cells of the heat map may be selected for display. Ferret is designed to assist bio scientists at different stages of research from early idea exploration to advanced analysis of results from bench experiments. Three live case studies in the field of plant biology are presented related to Arabidopsis thaliana. The first is to discover genes that may relate to the phenotype of open immature flower in Arabidopsis. The second case is about finding associations reported between ethylene signaling and a set of 300+ Arabidopsis genes. The third case is on searching for potential gene targets of an Arabidopsis transcription factor hypothesized to be involved in plant stress responses. Ferret was successful in finding valuable information in all three cases. In the first case the bZIP family of genes was identified. In the second case sentences indicating relevant associations were found in other species such as potato and jasmine. In the third sentences led to new research questions about the plant hormone salicylic acid. Ferret successfully

  20. Acute and chronic effects of ferret odor exposure in Sprague-Dawley rats.

    Science.gov (United States)

    Campeau, S; Nyhuis, T J; Sasse, S K; Day, H E W; Masini, C V

    2008-09-01

    This manuscript describes several behavioral and functional studies evaluating the capacity of ferret odors to elicit a number of acute and long-term responses in male Sprague-Dawley rats. Acute presentation elicits multiple responses, suggesting that ferret odor, likely from skin gland secretions, provides an anxiogenic-like stimulus in this strain of rats. Compared to cat odor, however, ferret odor did not produce rapid fear conditioning, a result perhaps attributable to methodological factors. Inactivation of the olfactory system and medial nucleus of the amygdala, combined with induction of the immediate-early gene c-fos, suggest the necessity of the accessory olfactory system in mediating the effects of ferret odor. Repeated exposures to ferret odor produce variable habituation of neuroendocrine and behavioral responses, perhaps indicative of the lack of control over the exact individual origin or concentration of ferret odor. Ferret odor induces rapid and long-term body weight regulation, thymic involution, adrenal hyperplasia and facilitation of the neuroendocrine response to additional challenges. It is argued that the use of such odors is exquisitely suited to investigate the brain regions coordinating anxiety-like responses and the long-term changes elicited by such stimuli.

  1. Mortality of Siberian polecats and black-footed ferrets released onto prairie dog colonies

    Science.gov (United States)

    Biggins, D.E.; Miller, B.J.; Hanebury, L.R.; Powell, R.A.

    2011-01-01

    Black-footed ferrets (Mustela nigripes) likely were extirpated from the wild in 19851986, and their repatriation depends on captive breeding and reintroduction. Postrelease survival of animals can be affected by behavioral changes induced by captivity. We released neutered Siberian polecats (M. eversmanii), close relatives of ferrets, in 19891990 on black-tailed prairie dog (Cynomys ludovicianus) colonies in Colorado and Wyoming initially to test rearing and reintroduction techniques. Captive-born polecats were reared in cages or cages plus outdoor pens, released from elevated cages or into burrows, and supplementally fed or not fed. We also translocated wild-born polecats from China in 1990 and released captive-born, cage-reared black-footed ferrets in 1991, the 1st such reintroduction of black-footed ferrets. We documented mortality for 55 of 92 radiotagged animals in these studies, mostly due to predation (46 cases). Coyotes (Canis latrans) killed 31 ferrets and polecats. Supplementally fed polecats survived longer than nonprovisioned polecats. With a model based on deaths per distance moved, survival was highest for wild-born polecats, followed by pen-experienced, then cage-reared groups. Indexes of abundance (from spotlight surveys) for several predators were correlated with mortality rates of polecats and ferrets due to those predators. Released black-footed ferrets had lower survival rates than their ancestral population in Wyoming, and lower survival than wild-born and translocated polecats, emphasizing the influence of captivity. Captive-born polecats lost body mass more rapidly postrelease than did captive-born ferrets. Differences in hunting efficiency and prey selection provide further evidence that these polecats and ferrets are not ecological equivalents in the strict sense. ?? 2011 American Society of Mammalogists.

  2. Cryptosporidium in ferret (Mustela putorius furo in the south of Brazil

    Directory of Open Access Journals (Sweden)

    Silvia Gonzalez Monteiro

    2010-03-01

    Full Text Available The aim of this research study was to evaluate the gastrointestinal parasitism in ferrets (Mustela putorius furo kept in captivity in the southern region of Brazil. Fecal samples of two three-year-old ferrets, a male and a female, were analyzed by the direct smear method, the centrifugal flotation technique with zinc sulfate, and tha Kinyoun staining method. Oocysts of Cryptosporidum sp. were observed in the faeces of both animals. This is the first report of this protozoan in ferrets in Brazil.

  3. The interaction between calreticulin and immunoglobulin G and immunoglobulin Y

    DEFF Research Database (Denmark)

    Møllegaard, Karen Mai; Duus, Karen; Træholt, Sofie Dietz

    2011-01-01

    accumulating in support of calreticulin as a polypeptide binding chaperone. In contrast to mammalian immunoglobulin G (IgG), which has complex type N-glycans, chicken immunoglobulin Y (IgY) possesses a monoglucosylated high mannose N-linked glycan, which is a ligand for calreticulin. Here, we have used solid...... and solution-phase assays to analyze the in vitro binding of calreticulin, purified from human placenta, to human IgG and chicken IgY in order to compare the interactions. In addition, peptides from the respective immunoglobulins were included to further probe the binding specificity of calreticulin....... The experiments demonstrate the ability of calreticulin to bind to denatured forms of both IgG and IgY regardless of the glycosylation state of the proteins. Furthermore, calreticulin exhibits binding to peptides (glycosylated and non-glycosylated) derived from trypsin digestion of both immunoglobulins...

  4. Spatial organization of astrocytes in ferret visual cortex

    Science.gov (United States)

    López‐Hidalgo, Mónica; Hoover, Walter B.

    2016-01-01

    ABSTRACT Astrocytes form an intricate partnership with neural circuits to influence numerous cellular and synaptic processes. One prominent organizational feature of astrocytes is the “tiling” of the brain with non‐overlapping territories. There are some documented species and brain region–specific astrocyte specializations, but the extent of astrocyte diversity and circuit specificity are still unknown. We quantitatively defined the rules that govern the spatial arrangement of astrocyte somata and territory overlap in ferret visual cortex using a combination of in vivo two‐photon imaging, morphological reconstruction, immunostaining, and model simulations. We found that ferret astrocytes share, on average, half of their territory with other astrocytes. However, a specific class of astrocytes, abundant in thalamo‐recipient cortical layers (“kissing” astrocytes), overlap markedly less. Together, these results demonstrate novel features of astrocyte organization indicating that different classes of astrocytes are arranged in a circuit‐specific manner and that tiling does not apply universally across brain regions and species. J. Comp. Neurol. 524:3561–3576, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:27072916

  5. Variable effects of soman on macromolecular secretion by ferret trachea

    Energy Technology Data Exchange (ETDEWEB)

    McBride, R.K.; Zwierzynski, D.J.; Stone, K.K.; Culp, D.J.; Marin, M.G. (Univ. of Rochester School of Medicine and Dentistry, NY (USA))

    1991-01-01

    The purpose of this study was to examine the effect of the anticholinesterase agent, soman, on macromolecular secretion by ferret trachea, in vitro. We mounted pieces of ferret trachea in Ussing-type chambers. Secreted sulfated macromolecules were radiolabeled by adding 500 microCi of {sup 35}SO{sub 4} to the submucosal medium and incubating for 17 hr. Soman added to the submucosal side produced a concentration-dependent increase in radiolabeled macromolecular release with a maximal secretory response (mean +/- SD) of 202 +/- 125% (n = 8) relative to the basal secretion rate at a concentration of 10{sup {minus} 7} M. The addition of either 10{sup {minus}6} M pralidoxime (acetylcholinesterase reactivator) or 10{sup {minus}6} M atropine blocked the response to 10{sup {minus}7} M soman. At soman concentrations greater than 10{sup {minus}7} M, secretion rate decreased and was not significantly different from basal secretion. Additional experiments utilizing acetylcholine and the acetylcholinesterase inhibitor, physostigmine, suggest that inhibition of secretion by high concentrations of soman may be due to a secondary antagonistic effect of soman on muscarinic receptors.

  6. Influenza vaccination accelerates recovery of ferrets from lymphopenia.

    Science.gov (United States)

    Music, Nedzad; Reber, Adrian J; Lipatov, Aleksandr S; Kamal, Ram P; Blanchfield, Kristy; Wilson, Jason R; Donis, Ruben O; Katz, Jacqueline M; York, Ian A

    2014-01-01

    Ferrets are a useful animal model for human influenza virus infections, since they closely mimic the pathogenesis of influenza viruses observed in humans. However, a lack of reagents, especially for flow cytometry of immune cell subsets, has limited research in this model. Here we use a panel of primarily species cross-reactive antibodies to identify ferret T cells, cytotoxic T lymphocytes (CTL), B cells, and granulocytes in peripheral blood. Following infection with seasonal H3N2 or H1N1pdm09 influenza viruses, these cell types showed rapid and dramatic changes in frequency, even though clinically the infections were mild. The loss of B cells and CD4 and CD8 T cells, and the increase in neutrophils, were especially marked 1-2 days after infection, when about 90% of CD8+ T cells disappeared from the peripheral blood. The different virus strains led to different kinetics of leukocyte subset alterations. Vaccination with homologous vaccine reduced clinical symptoms slightly, but led to a much more rapid return to normal leukocyte parameters. Assessment of clinical symptoms may underestimate the effectiveness of influenza vaccine in restoring homeostasis.

  7. Influenza vaccination accelerates recovery of ferrets from lymphopenia.

    Directory of Open Access Journals (Sweden)

    Nedzad Music

    Full Text Available Ferrets are a useful animal model for human influenza virus infections, since they closely mimic the pathogenesis of influenza viruses observed in humans. However, a lack of reagents, especially for flow cytometry of immune cell subsets, has limited research in this model. Here we use a panel of primarily species cross-reactive antibodies to identify ferret T cells, cytotoxic T lymphocytes (CTL, B cells, and granulocytes in peripheral blood. Following infection with seasonal H3N2 or H1N1pdm09 influenza viruses, these cell types showed rapid and dramatic changes in frequency, even though clinically the infections were mild. The loss of B cells and CD4 and CD8 T cells, and the increase in neutrophils, were especially marked 1-2 days after infection, when about 90% of CD8+ T cells disappeared from the peripheral blood. The different virus strains led to different kinetics of leukocyte subset alterations. Vaccination with homologous vaccine reduced clinical symptoms slightly, but led to a much more rapid return to normal leukocyte parameters. Assessment of clinical symptoms may underestimate the effectiveness of influenza vaccine in restoring homeostasis.

  8. Variable effects of soman on macromolecular secretion by ferret trachea

    International Nuclear Information System (INIS)

    McBride, R.K.; Zwierzynski, D.J.; Stone, K.K.; Culp, D.J.; Marin, M.G.

    1991-01-01

    The purpose of this study was to examine the effect of the anticholinesterase agent, soman, on macromolecular secretion by ferret trachea, in vitro. We mounted pieces of ferret trachea in Ussing-type chambers. Secreted sulfated macromolecules were radiolabeled by adding 500 microCi of 35 SO 4 to the submucosal medium and incubating for 17 hr. Soman added to the submucosal side produced a concentration-dependent increase in radiolabeled macromolecular release with a maximal secretory response (mean +/- SD) of 202 +/- 125% (n = 8) relative to the basal secretion rate at a concentration of 10 - 7 M. The addition of either 10 -6 M pralidoxime (acetylcholinesterase reactivator) or 10 -6 M atropine blocked the response to 10 -7 M soman. At soman concentrations greater than 10 -7 M, secretion rate decreased and was not significantly different from basal secretion. Additional experiments utilizing acetylcholine and the acetylcholinesterase inhibitor, physostigmine, suggest that inhibition of secretion by high concentrations of soman may be due to a secondary antagonistic effect of soman on muscarinic receptors

  9. The discovery of immunoglobulin E.

    Science.gov (United States)

    Ribatti, Domenico

    2016-03-01

    The discovery of immunoglobulin E (IgE) was a breakthrough in the field of allergy and immunology. Our understanding of mechanisms of allergic reactions and the role of IgE in these disorders has paralleled to the discovery of treatment modalities for patients with allergy. The first clue to the existence of a substance responsible for hypersensitivity reactions was demonstrated in 1921 by Prausnitz and Kustner, and after four decades it was identified as an immunoglobulin subclass by Ishizakas and co-workers. In 1968, the WHO International Reference Centre for Immunoglobulins announced the presence of a fifth immunoglobulin isotype, IgE. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Clinical applications of immunoglobulin: update

    Directory of Open Access Journals (Sweden)

    Marcia Cristina Zago Novaretti

    2011-06-01

    Full Text Available Human immunoglobulin is the most used blood product in the clinical practice. Immunoglobulin applications have increased quickly since the elucidation of its immunomodulatory and antiinflammatory properties which turned this blood product into a precious tool in the treatment of numerous diseases that present with humoral immune deficiency or that cause immune system dysfunction. Currently, the approved indications for Ig are: primary immunodeficiencies, secondary immunodeficiencies (multiple myeloma or chronic lymphoid leukemia, Kawasaki syndrome, immune thrombocytopenic purpura, Guillain Barré syndrome, graft-versus-host disease following bone marrow transplantation and repeat infections in HIV children. On the other hand, there are numerous "off-label" indications of immunoglobulin, which represent 20-60% of all clinical applications of this drug. It is important to study all these indications and, above all, the scientific evidence for its use, in order to provide patients with a new therapeutic option without burdening the health system. This review results from a wide selection of papers identified in the Pubmed and Lilacs scientific electronic databases. A group of descriptors were used from human immunoglobulin to the names of each disease that immunoglobulin is clinically applied. Our main objective is to list the numerous indications of immunoglobulin, both authorized and "off-label" and to analyze these indications in the light of the most recent scientific evidence.

  11. High-throughput immunophenotyping of 43 ferret lymphomas using tissue microarray technology

    DEFF Research Database (Denmark)

    Hammer, Anne Sofie; Williams, B.; Dietz, H.H.

    2007-01-01

    To validate the use of the tissue microarray (TMA) method for immunophenotyping of ferret lymphomas, a TMA was constructed containing duplicate 1-mm cores sampled from 112 paraffin-embedded lymphoma tissue specimens obtained from 43 ferret lymphoma cases. Immunohistochemical (IHC) expression of CD3......, CD79 alpha, and Ki-67 (MIB-1) was determined by TMA and whole mount (WM) staining of each individual case for result comparison. There was a high correlation between CD79 alpha and CD3 results comparing ferret TMA and WM sections (kappa statistic 0.71-0.73 for single-core TMA and 0.......79-0.95 for duplicate-core TMA) and between continuous data from Ki-67 staining of ferret TMA sections and WM sections (concordance correlation coefficients 0.77 for single cores and 0.87 for duplicate cores). Subsequently, a panel of commercially available antibodies was applied to the TMA for the analysis...

  12. Comparison of Responses in the Anterior and Primary Auditory Fields of the Ferret Cortex

    National Research Council Canada - National Science Library

    Kowalski, Nina; Versnel, Huib; Shamma, Shihab A

    1994-01-01

    Characteristics of an anterior auditory field (AAF) in the ferret auditory cortex are described in terms of its electrophysiological responses to tonal stimuli and compared to those of primary auditory cortex (AI...

  13. Inefficient transmission of H5N1 influenza viruses in a ferret contact model.

    Science.gov (United States)

    Yen, Hui-Ling; Lipatov, Aleksandr S; Ilyushina, Natalia A; Govorkova, Elena A; Franks, John; Yilmaz, Neziha; Douglas, Alan; Hay, Alan; Krauss, Scott; Rehg, Jerold E; Hoffmann, Erich; Webster, Robert G

    2007-07-01

    The abilities to infect and transmit efficiently among humans are essential for a novel influenza A virus to cause a pandemic. To evaluate the pandemic potential of widely disseminated H5N1 influenza viruses, a ferret contact model using experimental groups comprised of one inoculated ferret and two contact ferrets was used to study the transmissibility of four human H5N1 viruses isolated from 2003 to 2006. The effects of viral pathogenicity and receptor binding specificity (affinity to synthetic sialosaccharides with alpha2,3 or alpha2,6 linkages) on transmissibility were assessed. A/Vietnam/1203/04 and A/Vietnam/JP36-2/05 viruses, which possess "avian-like" alpha2,3-linked sialic acid (SA) receptor specificity, caused neurological symptoms and death in ferrets inoculated with 10(3) 50% tissue culture infectious doses. A/Hong Kong/213/03 and A/Turkey/65-596/06 viruses, which show binding affinity for "human-like" alpha2,6-linked SA receptors in addition to their affinity for alpha2,3-linked SA receptors, caused mild clinical symptoms and were not lethal to the ferrets. No transmission of A/Vietnam/1203/04 or A/Turkey/65-596/06 virus was detected. One contact ferret developed neutralizing antibodies to A/Hong Kong/213/03 but did not exhibit any clinical signs or detectable virus shedding. In two groups, one of two naïve contact ferrets had detectable virus after 6 to 8 days when housed together with the A/Vietnam/JP36-2/05 virus-inoculated ferrets. Infected contact ferrets showed severe clinical signs, although little or no virus was detected in nasal washes. This limited virus shedding explained the absence of secondary transmission from the infected contact ferret to the other naïve ferret that were housed together. Our results suggest that despite their receptor binding affinity, circulating H5N1 viruses retain molecular determinants that restrict their spread among mammalian species.

  14. Non-invasive blood pressure measurement in ferrets (Mustela putorius furo) using high definition oscillometry

    OpenAIRE

    van Zeeland, Y. R.A.; Wilde, A.; Bosman, I.H.; Uilenreef, J. J.; Egner, B.I.; Schoemaker, N. J.

    2017-01-01

    This study was conducted to validate the use of high definition oscillometry (HDO) for non-invasive blood pressure (NIBP) measurements in ferrets and to establish reference ranges for NIBP in minimally sedated, healthy, young adult ferrets (170 mmHg) conditions. Although HDO correlated well with DABP (r > 0.90), it showed significant proportional bias, whereby HDO generally underestimated DABP with hyper- and normotensive conditions, and overestimated DABP with hypotensive conditions. Measure...

  15. Jaundice and bilirubinemia as manifestations of canine distemper in raccoons and ferrets

    Science.gov (United States)

    Kilham, L.; Habermann, R.T.; Herman, C.M.

    1956-01-01

    1) Two strains of distemper virus have been isolated from wild raccoons and one strain from ferrets. 2) All strains isolated have induced bilirubinemia in raccoons and ferrets. Many raccoons with bilirubinemia also had jaundice. 3) Identification of these strains as members of the canine distemper virus complex has been by clinical and pathological findings consistent with this diagnosis as well as by cross-immunity tests.

  16. Electrochemotherapy with bleomycin of different types of cutaneous tumours in a ferret (Mustela putorius furo

    Directory of Open Access Journals (Sweden)

    Racnik Jozko

    2017-12-01

    Full Text Available Mast cell tumour, sebaceous gland adenoma, and less common squamous papilloma are skin tumours in ferrets (Mustela putorius furo, and early excisional surgery is usually the treatment of choice. The aim of our study was to investigate the effectiveness of electrochemotherapy (ECT, a new, minimally invasive non-surgical method, as first treatment option of different types of ferret skin tumours located on surgically difficult sites.

  17. Protecting Black-Footed Ferrets and Prairie Dogs Against Sylvatic Plague

    Science.gov (United States)

    Rocke, Tonie E.

    2008-01-01

    Scientists at the USGS National Wildlife Health Center (NWHC), in collaboration with colleagues at other federal agencies and the University of Wisconsin, are developing and testing vaccines that can be used to protect black-footed ferrets and prairie dogs against plague. The black-footed ferret is commonly regarded as the most endangered mammal in North America, and sylvatic plague is a major impediment to its recovery. The three prairie dog species (Gunnison's, black-tailed, and white-tailed prairie dogs), upon which the ferret depends for food and whose burrows they use for shelter, have been drastically reduced from historical levels, resulting in the near extinction of the ferret. All three species are considered 'at risk' and have been petitioned for listing as 'threatened' or 'endangered' by the U.S. Fish and Wildlife Service (FWS). Additionally, the Utah prairie dog is listed as threatened and the Mexican prairie dog is considered endangered in Mexico. Like the black-footed ferret, all five prairie dog species are highly susceptible to plague and regularly experience outbreaks with devastating losses. Controlling plague outbreaks in prairie dogs and ferrets is a vital concern for ongoing recovery programs and conservation efforts for both species.

  18. Cytokines as cellular communicators

    Directory of Open Access Journals (Sweden)

    R. Debets

    1996-01-01

    Full Text Available Cytokines and their receptors are involved in the pathophysiology of many diseases. Here we present a detailed review on cytokines, receptors and signalling routes, and show that one important lesson from cytokine biology is the complex and diverse regulation of cytokine activity. The activity of cytokines is controlled at the level of transcription, translation, storage, processing, posttranslational modification, trapping, binding by soluble proteins, and receptor number and/or function. Translation of this diverse regulation in strategies aimed at the control of cytokine activity will result in the development of more specific and selective drugs to treat diseases.

  19. Resource selection models are useful in predicting fine-scale distributions of black-footed ferrets in prairie dog colonies

    Science.gov (United States)

    Eads, David A.; Jachowski, David S.; Biggins, Dean E.; Livieri, Travis M.; Matchett, Marc R.; Millspaugh, Joshua J.

    2012-01-01

    Wildlife-habitat relationships are often conceptualized as resource selection functions (RSFs)—models increasingly used to estimate species distributions and prioritize habitat conservation. We evaluated the predictive capabilities of 2 black-footed ferret (Mustela nigripes) RSFs developed on a 452-ha colony of black-tailed prairie dogs (Cynomys ludovicianus) in the Conata Basin, South Dakota. We used the RSFs to project the relative probability of occurrence of ferrets throughout an adjacent 227-ha colony. We evaluated performance of the RSFs using ferret space use data collected via postbreeding spotlight surveys June–October 2005–2006. In home ranges and core areas, ferrets selected the predicted "very high" and "high" occurrence categories of both RSFs. Count metrics also suggested selection of these categories; for each model in each year, approximately 81% of ferret locations occurred in areas of very high or high predicted occurrence. These results suggest usefulness of the RSFs in estimating the distribution of ferrets throughout a black-tailed prairie dog colony. The RSFs provide a fine-scale habitat assessment for ferrets that can be used to prioritize releases of ferrets and habitat restoration for prairie dogs and ferrets. A method to quickly inventory the distribution of prairie dog burrow openings would greatly facilitate application of the RSFs.

  20. The mouse and ferret models for studying the novel avian-origin human influenza A (H7N9) virus.

    Science.gov (United States)

    Xu, Lili; Bao, Linlin; Deng, Wei; Zhu, Hua; Chen, Ting; Lv, Qi; Li, Fengdi; Yuan, Jing; Xiang, Zhiguang; Gao, Kai; Xu, Yanfeng; Huang, Lan; Li, Yanhong; Liu, Jiangning; Yao, Yanfeng; Yu, Pin; Yong, Weidong; Wei, Qiang; Zhang, Lianfeng; Qin, Chuan

    2013-08-08

    The current study was conducted to establish animal models (including mouse and ferret) for the novel avian-origin H7N9 influenza virus. A/Anhui/1/2013 (H7N9) virus was administered by intranasal instillation to groups of mice and ferrets, and animals developed typical clinical signs including body weight loss (mice and ferrets), ruffled fur (mice), sneezing (ferrets), and death (mice). Peak virus shedding from respiratory tract was observed on 2 days post inoculation (d.p.i.) for mice and 3-5 d.p.i. for ferrets. Virus could also be detected in brain, liver, spleen, kidney, and intestine from inoculated mice, and in heart, liver, and olfactory bulb from inoculated ferrets. The inoculation of H7N9 could elicit seroconversion titers up to 1280 in ferrets and 160 in mice. Leukopenia, significantly reduced lymphocytes but increased neutrophils were also observed in mouse and ferret models. The mouse and ferret model enables detailed studies of the pathogenesis of this illness and lay the foundation for drug or vaccine evaluation.

  1. [Multiple myeloma with D immunoglobulin].

    Science.gov (United States)

    Benchekroun, Laila; Ouzzif, Zohra; Bouabdillah, Mounya; Jaouhar, Nouzha; Aoufir, Fatiha; Aoufi, Farida; Chabraoui, Layachi

    2011-01-01

    The immunoglobulin D multiple myeloma is a rare form of multiple myeloma and affects a young population. It is characterized by its clinical severity and poor prognosis. We report four cases of multiple myeloma immunoglobulin D diagnosed and supported in the university hospital Center of Sale and Rabat-Morocco. We propose to study the epidemiological, clinical and biological characteristics of this rare type of monoclonal gammopathy. Through the observations reported, the clinical aspect of myeloma is characterized by the high frequency of extra-bone manifestations including impaired kidney function. The immunoglobulin D multiple myeloma is mainly type λ, the IgD κ is rare, the predominance of λ light chains could be explained by rearrangements at the immunoglobulin genes. Bence-Jones proteinuria is almost constant in the multiple myeloma immunoglobulin D, it is mainly type λ, reflecting excess production of light chains by plasma cells. The marrow is invaded by plasma cells in very different proportions of up to 95%. It's a clinical entity, difficult to diagnose, particularly when low homogeneous band on electrophoresis goes unnoticed for an eye inexperienced or when immune serum anti-IgD was not used during the immunotyping.

  2. Cytokines in Drosophila immunity.

    Science.gov (United States)

    Vanha-Aho, Leena-Maija; Valanne, Susanna; Rämet, Mika

    2016-02-01

    Cytokines are a large and diverse group of small proteins that can affect many biological processes, but most commonly cytokines are known as mediators of the immune response. In the event of an infection, cytokines are produced in response to an immune stimulus, and they function as key regulators of the immune response. Cytokines come in many shapes and sizes, and although they vary greatly in structure, their functions have been well conserved in evolution. The immune signaling pathways that respond to cytokines are remarkably conserved from fly to man. Therefore, Drosophila melanogaster, provides an excellent platform for studying the biology and function of cytokines. In this review, we will describe the cytokines and cytokine-like molecules found in the fly and discuss their roles in host immunity. Copyright © 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  3. Enzootic plague reduces black-footed ferret (Mustela nigripes) survival in Montana.

    Science.gov (United States)

    Matchett, Marc R; Biggins, Dean E; Carlson, Valerie; Powell, Bradford; Rocke, Tonie

    2010-01-01

    Black-footed ferrets (Mustela nigripes) require extensive prairie dog colonies (Cynomys spp.) to provide habitat and prey. Epizootic plague kills both prairie dogs and ferrets and is a major factor limiting recovery of the highly endangered ferret. In addition to epizootics, we hypothesized that enzootic plague, that is, presence of disease-causing Yersinia pestis without any noticeable prairie dog die off, may also affect ferret survival. We reduced risk of plague on portions of two ferret reintroduction areas by conducting flea control for 3 years. Beginning in 2004, about half of the ferrets residing on dusted and nondusted colonies were vaccinated against plague with an experimental vaccine (F1-V fusion protein). We evaluated 6-month reencounter rates (percentage of animals observed at the end of an interval that were known alive at the beginning of the interval), an index to survival, for ferrets in four treatment groups involving all combinations of vaccination and flea control. For captive-reared ferrets (115 individuals observed across 156 time intervals), reencounter rates were higher for vaccinates (0.44) than for nonvaccinates (0.23, p = 0.044) on colonies without flea control, but vaccination had no detectable effect on colonies with flea control (vaccinates = 0.41, nonvaccinates = 0.42, p = 0.754). Flea control resulted in higher reencounter rates for nonvaccinates (p = 0.026), but not for vaccinates (p = 0.508). The enhancement of survival due to vaccination or flea control supports the hypothesis that enzootic plague reduces ferret survival, even when there was no noticeable decline in prairie dog abundance. The collective effects of vaccination and flea control compel a conclusion that fleas are required for maintenance, and probably transmission, of plague at enzootic levels. Other studies have demonstrated similar effects of flea control on several species of prairie dogs and, when combined with this study, suggest that the effects of enzootic

  4. Cytokines cause functional and structural damage to isolated islets of Langerhans

    DEFF Research Database (Denmark)

    Mandrup-Poulsen, T; Bendtzen, K; Bendixen, G

    1985-01-01

    Cytokines are soluble, antigen non-specific, non-immunoglobulin mediators produced and secreted by blood mononuclear cells interacting in the cellular immune-response. To test the possibility that cytokines participate in the autoimmune destruction of the pancreatic beta-cells leading to insulin-......-release, and contents of insulin and glucagon in islets incubated with cytokine-rich supernatants were markedly reduced. This impairment of islet function was due to a cytotoxic effect of cytokine-rich supernatants as judged by disintegration of normal light-microscopic morphology....

  5. Ferret badger rabies origin and its revisited importance as potential source of rabies transmission in Southeast China

    Directory of Open Access Journals (Sweden)

    Liu Ye

    2010-08-01

    Full Text Available Abstract Background The frequent occurrence of ferret badger-associated human rabies cases in southeast China highlights the lack of laboratory-based surveillance and urges revisiting the potential importance of this animal in rabies transmission. To determine if the ferret badgers actually contribute to human and dog rabies cases, and the possible origin of the ferret badger-associated rabies in the region, an active rabies survey was conducted to determine the frequency of rabies infection and seroprevalence in dogs and ferret badgers. Methods A retrospective survey on rabies epidemics was performed in Zhejiang, Jiangxi and Anhui provinces in southeast China. The brain tissues from ferret badgers and dogs were assayed by fluorescent antibody test. Rabies virus was isolated and sequenced for phylogenetic analysis. The sera from ferret badgers and dogs were titrated using rabies virus neutralizing antibodies (VNA test. Results The ferret badgers presented a higher percentage of rabies seroconversion than dogs did in the endemic region, reaching a maximum of 95% in the collected samples. Nine ferret badger-associated rabies viruses were isolated, sequenced, and were phylogenetically clustered as a separate group. Nucleotide sequence revealed 99.4-99.8% homology within the ferret badger isolates, and 83-89% homology to the dog isolates in the nucleoprotein and glycoprotein genes in the same rabies endemic regions. Conclusions Our data suggest ferret badger-associated rabies has likely formed as an independent enzootic originating from dogs during the long-term rabies infestation in southeast China. The eventual role of FB rabies in public health remains unclear. However, management of ferret badger bites, rabies awareness and control in the related regions should be an immediate need.

  6. Lack of innate interferon responses during SARS coronavirus infection in a vaccination and reinfection ferret model.

    Directory of Open Access Journals (Sweden)

    Mark J Cameron

    Full Text Available In terms of its highly pathogenic nature, there remains a significant need to further define the immune pathology of SARS-coronavirus (SARS-CoV infection, as well as identify correlates of immunity to help develop vaccines for severe coronaviral infections. Here we use a SARS-CoV infection-reinfection ferret model and a functional genomics approach to gain insight into SARS immunopathogenesis and to identify correlates of immune protection during SARS-CoV-challenge in ferrets previously infected with SARS-CoV or immunized with a SARS virus vaccine. We identified gene expression signatures in the lungs of ferrets associated with primary immune responses to SARS-CoV infection and in ferrets that received an identical second inoculum. Acute SARS-CoV infection prompted coordinated innate immune responses that were dominated by antiviral IFN response gene (IRG expression. Reinfected ferrets, however, lacked the integrated expression of IRGs that was prevalent during acute infection. The expression of specific IRGs was also absent upon challenge in ferrets immunized with an inactivated, Al(OH(3-adjuvanted whole virus SARS vaccine candidate that protected them against SARS-CoV infection in the lungs. Lack of IFN-mediated immune enhancement in infected ferrets that were previously inoculated with, or vaccinated against, SARS-CoV revealed 9 IRG correlates of protective immunity. This data provides insight into the molecular pathogenesis of SARS-CoV and SARS-like-CoV infections and is an important resource for the development of CoV antiviral therapeutics and vaccines.

  7. Interactions among American badgers, black-footed ferrets, and prairie dogs in the grasslands of western North America

    Science.gov (United States)

    Eads, David A.; Biggins, Dean E.; Grassel, Shaun M.; Livieri, Travis M.; Licht, Daniel S.; Proulx, Gilbert; Do Linh San, Emmanuel

    2016-01-01

    American badgers (Taxidea taxus) and black-footed ferrets (Mustela nigripes) sometimes occur sympatrically within colonies of prairie dogs (Cynomys spp.) in the grasslands of western North America. From the perspective of a simplified food web, badgers are consumers of ferrets and, to a greater extent, prairie dogs; ferrets are specialized consumers of prairie dogs; and prairie dogs are consumers of vegetation. We review information on the predatory behaviours of badgers, which collectively demonstrate that badgers exhibit complex hunting strategies to improve their probability of capturing prairie dogs and, perhaps, ferrets. We also review studies of interactions between badgers and ferrets, which suggest that there is selective pressure on badgers to compete with ferrets, and pressure on ferrets to compete with and avoid badgers. We then speculate as to how prairie dogs might shape interactions between badgers and ferrets, and how badgers could spread the plague bacterium (Yersinia pestis) among prairie dog colonies. Lastly, we provide recommendations for research on this tractable system of semi-fossorial predators and prey.

  8. 78 FR 77485 - Endangered and Threatened Wildlife and Plants; Revised Recovery Plan for the Black-Footed Ferret

    Science.gov (United States)

    2013-12-23

    ... estimates of the time and cost for implementing the needed recovery measures. The Act requires recovery...-footed ferret. In this final revised plan, we have summarized and responded to the issues raised by both... ferret habitat has been dramatically reduced from historical times, a sufficient amount remains if its...

  9. Liposome-based cationic adjuvant CAF01 enhances the protection conferred by a commercial inactivated influenza vaccine in ferrets

    DEFF Research Database (Denmark)

    Martel, Cyril Jean-Marie; Agger, Else Marie; Jensen, Trine Hammer

    Objectives: To assess the effect of CAF01 adjuvant associated to a commercial trivalent inactivated influenza vaccine in the ferret model. Methods:  Ferrets were vaccinated with a range of doses of Sanofi-Pasteur's Vaxigrip with or without the CAF01 adjuvant, and challenged with either one of two H...

  10. A novel video tracking method to evaluate the effect of influenza infection and antiviral treatment on ferret activity.

    Science.gov (United States)

    Oh, Ding Yuan; Barr, Ian G; Hurt, Aeron C

    2015-01-01

    Ferrets are the preferred animal model to assess influenza virus infection, virulence and transmission as they display similar clinical symptoms and pathogenesis to those of humans. Measures of disease severity in the ferret include weight loss, temperature rise, sneezing, viral shedding and reduced activity. To date, the only available method for activity measurement has been the assignment of an arbitrary score by a 'blind' observer based on pre-defined responsiveness scale. This manual scoring method is subjective and can be prone to bias. In this study, we described a novel video-tracking methodology for determining activity changes in a ferret model of influenza infection. This method eliminates the various limitations of manual scoring, which include the need for a sole 'blind' observer and the requirement to recognise the 'normal' activity of ferrets in order to assign relative activity scores. In ferrets infected with an A(H1N1)pdm09 virus, video-tracking was more sensitive than manual scoring in detecting ferret activity changes. Using this video-tracking method, oseltamivir treatment was found to ameliorate the effect of influenza infection on activity in ferret. Oseltamivir treatment of animals was associated with an improvement in clinical symptoms, including reduced inflammatory responses in the upper respiratory tract, lower body weight loss and a smaller rise in body temperature, despite there being no significant reduction in viral shedding. In summary, this novel video-tracking is an easy-to-use, objective and sensitive methodology for measuring ferret activity.

  11. A novel video tracking method to evaluate the effect of influenza infection and antiviral treatment on ferret activity.

    Directory of Open Access Journals (Sweden)

    Ding Yuan Oh

    Full Text Available Ferrets are the preferred animal model to assess influenza virus infection, virulence and transmission as they display similar clinical symptoms and pathogenesis to those of humans. Measures of disease severity in the ferret include weight loss, temperature rise, sneezing, viral shedding and reduced activity. To date, the only available method for activity measurement has been the assignment of an arbitrary score by a 'blind' observer based on pre-defined responsiveness scale. This manual scoring method is subjective and can be prone to bias. In this study, we described a novel video-tracking methodology for determining activity changes in a ferret model of influenza infection. This method eliminates the various limitations of manual scoring, which include the need for a sole 'blind' observer and the requirement to recognise the 'normal' activity of ferrets in order to assign relative activity scores. In ferrets infected with an A(H1N1pdm09 virus, video-tracking was more sensitive than manual scoring in detecting ferret activity changes. Using this video-tracking method, oseltamivir treatment was found to ameliorate the effect of influenza infection on activity in ferret. Oseltamivir treatment of animals was associated with an improvement in clinical symptoms, including reduced inflammatory responses in the upper respiratory tract, lower body weight loss and a smaller rise in body temperature, despite there being no significant reduction in viral shedding. In summary, this novel video-tracking is an easy-to-use, objective and sensitive methodology for measuring ferret activity.

  12. Environmental enrichment affects adrenocortical stress responses in the endangered black-footed ferret

    Science.gov (United States)

    Poessel, S.A.; Biggins, D.E.; Santymire, R.M.; Livieri, T.M.; Crooks, K.R.; Angeloni, L.

    2011-01-01

    Potential stressors of wildlife living in captivity, such as artificial living conditions and frequent human contact, may lead to a higher occurrence of disease and reduced reproductive function. One successful method used by wildlife managers to improve general well-being is the provision of environmental enrichment, which is the practice of providing animals under managed care with environmental stimuli. The black-footed ferret (Mustela nigripes) is a highly-endangered carnivore species that was rescued from extinction by removal of the last remaining individuals from the wild to begin an ex situ breeding program. Our goal was to examine the effect of environmental enrichment on adrenocortical activity in ferrets by monitoring fecal glucocorticoid metabolites (FGM). Results demonstrated that enrichment lowered FGM in juvenile male ferrets, while increasing it in adult females; enrichment had no effect on FGM in juvenile females and adult males. These results correspond with our findings that juvenile males interacted more with the enrichment items than did adult females. However, we did not detect an impact of FGM on the incidence of disease or on the ability of ferrets to become reproductive during the following breeding season. We conclude that an environmental enrichment program could benefit captive juvenile male ferrets by reducing adrenocortical activity. ?? 2011 Elsevier Inc.

  13. Characterization of the Localized Immune Response in the Respiratory Tract of Ferrets following Infection with Influenza A and B Viruses.

    Science.gov (United States)

    Carolan, Louise A; Rockman, Steve; Borg, Kathryn; Guarnaccia, Teagan; Reading, Patrick; Mosse, Jennifer; Kelso, Anne; Barr, Ian; Laurie, Karen L

    2015-12-30

    The burden of infection with seasonal influenza viruses is significant. Each year is typically characterized by the dominance of one (sub)type or lineage of influenza A or B virus, respectively. The incidence of disease varies annually, and while this may be attributed to a particular virus strain or subtype, the impacts of prior immunity, population differences, and variations in clinical assessment are also important. To improve our understanding of the impacts of seasonal influenza viruses, we directly compared clinical symptoms, virus shedding, and expression of cytokines, chemokines, and immune mediators in the upper respiratory tract (URT) of ferrets infected with contemporary A(H1N1)pdm09, A(H3N2), or influenza B virus. Gene expression in the lower respiratory tract (LRT) was also assessed. Clinical symptoms were minimal. Overall cytokine/chemokine profiles in the URT were consistent in pattern and magnitude between animals infected with influenza A and B viruses, and peak expression levels of interleukin-1α (IL-1α), IL-1β, IL-6, IL-12p40, alpha interferon (IFN-α), IFN-β, and tumor necrosis factor alpha (TNF-α) mRNAs correlated with peak levels of viral shedding. MCP1 and IFN-γ were expressed after the virus peak. Granzymes A and B and IL-10 reached peak expression as the virus was cleared and seroconversion was detected. Cytokine/chemokine gene expression in the LRT following A(H1N1)pdm09 virus infection reflected the observations seen for the URT but was delayed 2 or 3 days, as was virus replication. These data indicate that disease severities and localized immune responses following infection with seasonal influenza A and B viruses are similar, suggesting that other factors are likely to modulate the incidence and impact of seasonal influenza. Both influenza A and B viruses cocirculate in the human population, and annual influenza seasons are typically dominated by an influenza A virus subtype or an influenza B virus lineage. Surveillance data

  14. Evaluation of a candidate live attenuated influenza vaccine prepared in Changchun BCHT (China) for safety and efficacy in ferrets.

    Science.gov (United States)

    Shen, Zhenwei; Bowen, Richard A; Ge, Peng; Yu, Jinfei; Shen, Yanjie; Kong, Wei; Jiang, Chunlai; Wu, Jinchang; Zhu, Changlin; Xu, Yanjun; Wei, Wei; Rudenko, Larisa; Kiseleva, Irina; Xu, Fei

    2016-11-21

    We evaluated the safety and efficacy of a live attenuated influenza vaccine (LAIV) product in ferrets. The BCHT LAIV product was significantly less virulent than wild-type H1N1 virus, when evaluated by comparing virus shedding and histopathologic lesions. The data indicated strong evidence for an attenuated phenotype of LAIV. Furthermore, the vaccine induced robust humoral immune responses in seronegative ferrets, and protected ferrets against development of fever, weight loss and turbinate inflammatory lesions after challenging with H3N2 wide-type influenza virus. Thus, the BCHT LAIV product was safe in healthy seronegative ferrets and protected ferrets against infection of H3N2 influenza virus. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Remodeling of inhibitory synaptic connections in developing ferret visual cortex

    Directory of Open Access Journals (Sweden)

    Dalva Matthew B

    2010-02-01

    Full Text Available Abstract Background In the visual cortex, as in many other regions of the developing brain, excitatory synaptic connections undergo substantial remodeling during development. While evidence suggests that local inhibitory synapses may behave similarly, the extent and mechanisms that mediate remodeling of inhibitory connections are not well understood. Results Using scanning laser photostimulation in slices of developing ferret visual cortex, we assessed the overall patterns of developing inhibitory and excitatory synaptic connections converging onto individual neurons. Inhibitory synaptic inputs onto pyramidal neurons in cortical layers 2 and 3 were already present as early as postnatal day 20, well before eye opening, and originated from regions close to the recorded neurons. During the ensuing 2 weeks, the numbers of synaptic inputs increased, with the numbers of inhibitory (and excitatory synaptic inputs peaking near the time of eye opening. The pattern of inhibitory inputs refined rapidly prior to the refinement of excitatory inputs. By uncaging the neurotransmtter GABA in brain slices from animals of different ages, we find that this rapid refinement correlated with a loss of excitatory activity by GABA. Conclusion Inhibitory synapses, like excitatory synapses, undergo significant postnatal remodeling. The time course of the remodeling of inhibitory connections correlates with the emergence of orientation tuning in the visual cortex, implicating these rearrangements in the genesis of adult cortical response properties.

  16. Immunoglobulin E and G4 antibody responses in occupational airway exposure to bovine and porcine plasma proteins

    NARCIS (Netherlands)

    Krop, E. J. M.; Stapel, S. O.; de Vrieze, H.; van der Zee, J. S.

    2006-01-01

    BACKGROUND: Production of both antigen-specific immunoglobulin (Ig)E and IgG4 antibodies is dependent on stimulation of B cells by T helper 2 cell-derived cytokines. However, there is controversy as to their interaction. In this study, we investigated the interdependency of IgE and IgG4 antibody

  17. Black-footed ferret areas of activity during late summer and fall at Meeteetse, Wyoming

    Science.gov (United States)

    Fagerstone, K.A.; Biggins, D.E.

    2011-01-01

    Radiotelemetry was used during 1983 and 1984 to collect information on short-term areas of activity for black-footed ferrets (Mustela nigripes) near Meeteetse, Wyoming. This population ultimately provided ferrets for the captive-breeding program that bred and released offspring into the wild since 1991. We fitted 5 adult ferrets and 13 juveniles with radiotransmitters and followed their movements during late summer and fall. Adult males had 7-day areas of activity that were >6 times as large as those of adult females. Activity areas of adult males varied little in coverage or location on a weekly basis, but females sequentially shifted their areas. Unlike juvenile females, juvenile males tended to leave their natal colonies. ?? 2011 American Society of Mammalogists.

  18. Non-invasive blood pressure measurement in ferrets (Mustela putorius furo) using high definition oscillometry.

    Science.gov (United States)

    van Zeeland, Y R A; Wilde, A; Bosman, I H; Uilenreef, J J; Egner, B; Schoemaker, N J

    2017-10-01

    This study was conducted to validate the use of high definition oscillometry (HDO) for non-invasive blood pressure (NIBP) measurements in ferrets and to establish reference ranges for NIBP in minimally sedated, healthy, young adult ferrets (170mmHg) conditions. Although HDO correlated well with DABP (r>0.90), it showed significant proportional bias, whereby HDO generally underestimated DABP with hyper- and normotensive conditions, and overestimated DABP with hypotensive conditions. Measurements obtained from the hind limb showed higher bias than those obtained from the tail or forelimb (Pyoung adult ferrets were established at 95-155mmHg (systolic), 69-109mmHg (mean) and 51-87mmHg (diastolic) arterial pressures. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Basal metabolism of the black-footed ferret (Mustela nigripes) and the Siberian polecat (M. eversmannii)

    Science.gov (United States)

    Harrington, L.A.; Biggins, D.E.; Alldredge, A.W.

    2003-01-01

    Black-footed ferrets (Mustela nigripes) and Siberian polecats (M. eversmannii) are medium-sized (about 1 kg) mustelids with similar ecological and morphological characteristics. We measured basal metabolic rates (BMR) for both species. In contrast with the commonly stated belief that mustelids have relatively high mass-specific BMR, neither the BMR of ferrets nor that of polecats in winter was greater than standard allometric predictions for all mammals. As suggested by previous authors, we believe that our relatively lower measurements for BMR are due to our efforts to minimize stress during the experimental procedure. These results support the contention that BMR in mustelids is no different from what is expected of mammals of this body mass. Seasonal differences were found in polecat BMR (higher in summer) but not in ferret BMR. Reasons for this interspecific difference may relate to differences in natural histories of these species.

  20. Cytokines and intestinal inflammation.

    Science.gov (United States)

    Bamias, Giorgos; Cominelli, Fabio

    2016-11-01

    Cytokines of the intestinal microenvironment largely dictate immunological responses after mucosal insults and the dominance of homeostatic or proinflammatory pathways. This review presents important recent studies on the role of specific cytokines in the pathogenesis of intestinal inflammation. The particular mucosal effects of cytokines depend on their inherent properties but also the cellular origin, type of stimulatory antigens, intermolecular interactions, and the particular immunological milieu. Novel cytokines of the interleukin-1 (IL-1) family, including IL-33 and IL-36, have dominant roles in mucosal immunity, whereas more established ones such as IL-18 are constantly enriched with unique properties. Th17 cells are important mucosal constituents, although their profound plasticity, makes the specific set of cytokines they secrete more important than their mere numbers. Finally, various cytokines, such as tumor necrosis factor-α, IL-6, tumor necrosis factor-like cytokine 1A, and death receptor, 3 demonstrate dichotomous roles with mucosa-protective function in acute injury but proinflammatory effects during chronic inflammation. The role of cytokines in mucosal health and disease is increasingly revealed. Such information not only will advance our understanding of the pathogenesis of gut inflammation, but also set the background for development of reliable diagnostic and prognostic biomarkers and cytokine-specific therapies.

  1. The quest for a safe and effective canine distemper virus vaccine for black-footed ferrets

    Science.gov (United States)

    Wimsatt, Jeffrey; Biggins, Dean E.; Williams, Elizabeth S.; Becerra, Victor M.

    2006-01-01

    Canine distemper virus (CDV) causes a systemic disease that is highly virulent to mustelids and other carnivore (Order Carnivora) species and is found worldwide. Endemic canine distemper in wild and domestic carnivores in the United States has made reintroduction of endangered black-footed ferrets (Mustela nigripes) difficult in the absence of safe and effective CDV vaccines and vaccination practices. Toward this end, researchers have explored appropriate animal models and vaccine preparations in highly susceptible species. Published studies involving domestic ferrets (M. putorius furo) using Galaxy-D® and evaluating a recombinant canarypox-vectored vaccine for oral administration are reviewed. In addition, we present new findings in domestic and black-footed ferrets and Siberian polecats (M. eversmannii) that have extended our understanding of CDV in the black-footed ferret and other at-risk carnivore species. Original research presented here includes trials that determined an effective challenge dose (by route) of virulent CDV in domestic ferrets and Siberian polecats; the low likelihood of collateral vaccination with Galaxy-D; the adverse effect of modified-live virus boostering in black-footed ferrets receiving killed vaccine previously and the response of Siberian polecats receiving canarypoxvectored recombinant CDV vaccine (reCDV); the absence of an effect of reCDV vaccination on conception, pregnancy, and neonatal growth in Siberian polecats; and the apparent inefficacy of active reCDV vaccination during the period of passive immunity in young Siberian polecats. In the final section, we discuss emerging concerns and avenues for disease intervention that may present new opportunities to solve problems in vaccine safety, vaccine availability, field vaccine delivery, and other therapeutic modalities.

  2. Anti-inflammatory and immunomodulatory potential of human immunoglobulin applied intrathecally in Lewis rat experimental autoimmune neuritis.

    Science.gov (United States)

    Pitarokoili, Kalliopi; Kohle, Felix; Motte, Jeremias; Fatoba, Oluwaseun; Pedreiturria, Xiomara; Gold, Ralf; Yoon, Min-Suk

    2017-08-15

    Intravenous human immunoglobulins dominate in the treatment of autoimmune neuropathies. We introduce intrathecal application as a new option for experimental autoimmune neuritis in Lewis rats. After immunisation with neuritogenic P2 peptide, we show a therapeutic and preventive effect of intrathecal human immunoglobulins (5-40mg/kg) on clinical and electrophysiological neuritis signs. Histology corroborated a lower degree of inflammation, demyelination, ICAM-1-dependent blood-nerve-barrier permeability and complement activation in the sciatic nerve. After preventive application, immunoglobulins induced a Th2 cytokine shift in the peripheral nerves already before clinical neuritis signs. Intrathecal immunoglobulin application could be a novel immunomodulatory option for autoimmune neuropathies. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Cytokines and intraocular inflammation

    NARCIS (Netherlands)

    Hoekzema, R.; Murray, P. I.; Kijlstra, A.

    1990-01-01

    Although new endogenous mediators of inflammatory and immune responses are reported almost on a monthly basis, the cytokines IL-1, TNF, and IL-6 have emerged as the primary regulators of local inflammation in man. In this paper, uveitogenic and other properties of these particular cytokines are

  4. Production of infectious ferret hepatitis E virus in a human hepatocarcinoma cell line PLC/PRF/5.

    Science.gov (United States)

    Li, Tian-Cheng; Yoshizaki, Sayaka; Yang, Tingting; Kataoka, Michiyo; Nakamura, Tomofumi; Ami, Yasushi; Yuriko, Suzaki; Takeda, Naokazu; Wakita, Takaji

    2016-02-02

    A strain of ferret hepatitis E virus (HEV), sF4370, isolated from an imported ferret was used to inoculate a human hepatocarcinoma cell line, PLC/PRF/5. The virus genome and capsid protein were detected in the cell culture supernatant. Immunofluorescence microscopy indicated that the capsid protein was located in the cytoplasm. The virus particles were purified from the culture supernatant by sucrose gradient ultracentrifugation. The capsid protein with molecular mass of ∼72 kDa was detected in fractions with density of 1.150-1.162 g/cm(3), and particles of ferret HEV was associated with cell membrane. The virus recovered from the supernatant was serially passaged with PLC/PRF/5 cells and had the ability to infect ferrets by oral inoculation, indicating that the ferret HEV grown in PLC/PRF/5 was infectious. The establishment of ferret HEV cell culture system might be useful to understand the life cycle, mechanism of infection and replication of ferret HEV. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Black-footed ferrets and recreational shooting influence the attributes of black-tailed prairie dog burrows

    Science.gov (United States)

    Biggins, Dean E.; Ramakrishnan, Shantini; Goldberg, Amanda R.; Eads, David A.

    2012-01-01

    Black-tailed prairie dogs (Cynomys ludovicianus) plug burrows occupied by black-footed ferrets (Mustela nigripes), and they also plug burrows to entomb dead prairie dogs. We further evaluated these phenomena by sampling connectivity and plugging of burrow openings on prairie dog colonies occupied by ferrets, colonies where recreational shooting was allowed, and colonies with neither shooting nor ferrets. We counted burrow openings on line surveys and within plots, classified surface plugging, and used an air blower to examine subsurface connectivity. Colonies with ferrets had lower densities of openings, fewer connected openings (suggesting increased subsurface plugging), and more surface plugs compared to colonies with no known ferrets. Colonies with recreational shooting had the lowest densities of burrow openings, and line-survey data suggested colonies with shooting had intermediate rates of surface plugging. The extent of surface and subsurface plugging could have consequences for the prairie dog community by changing air circulation and escape routes of burrow systems and by altering energetic relationships. Burrow plugging might reduce prairie dogs' risk of predation by ferrets while increasing risk of predation by American badgers (Taxidea taxus); however, the complexity of the trade-off is increased if plugging increases the risk of predation on ferrets by badgers. Prairie dogs expend more energy plugging and digging when ferrets or shooting are present, and ferrets increase their energy expenditures when they dig to remove those plugs. Microclimatic differences in plugged burrow systems may play a role in flea ecology and persistence of the flea-borne bacterium that causes plague (Yersinia pestis).

  6. Delineating morbillivirus entry, dissemination and airborne transmission by studying in vivo competition of multicolor canine distemper viruses in ferrets.

    Science.gov (United States)

    de Vries, Rory D; Ludlow, Martin; de Jong, Alwin; Rennick, Linda J; Verburgh, R Joyce; van Amerongen, Geert; van Riel, Debby; van Run, Peter R W A; Herfst, Sander; Kuiken, Thijs; Fouchier, Ron A M; Osterhaus, Albert D M E; de Swart, Rik L; Duprex, W Paul

    2017-05-01

    Identification of cellular receptors and characterization of viral tropism in animal models have vastly improved our understanding of morbillivirus pathogenesis. However, specific aspects of viral entry, dissemination and transmission remain difficult to recapitulate in animal models. Here, we used three virologically identical but phenotypically distinct recombinant (r) canine distemper viruses (CDV) expressing different fluorescent reporter proteins for in vivo competition and airborne transmission studies in ferrets (Mustela putorius furo). Six donor ferrets simultaneously received three rCDVs expressing green, red or blue fluorescent proteins via conjunctival (ocular, Oc), intra-nasal (IN) or intra-tracheal (IT) inoculation. Two days post-inoculation sentinel ferrets were placed in physically separated adjacent cages to assess airborne transmission. All donor ferrets developed lymphopenia, fever and lethargy, showed progressively increasing systemic viral loads and were euthanized 14 to 16 days post-inoculation. Systemic replication of virus inoculated via the Oc, IN and IT routes was detected in 2/6, 5/6 and 6/6 ferrets, respectively. In five donor ferrets the IT delivered virus dominated, although replication of two or three different viruses was detected in 5/6 animals. Single lymphocytes expressing multiple fluorescent proteins were abundant in peripheral blood and lymphoid tissues, demonstrating the occurrence of double and triple virus infections. Transmission occurred efficiently and all recipient ferrets showed evidence of infection between 18 and 22 days post-inoculation of the donor ferrets. In all cases, airborne transmission resulted in replication of a single-colored virus, which was the dominant virus in the donor ferret. This study demonstrates that morbilliviruses can use multiple entry routes in parallel, and co-infection of cells during viral dissemination in the host is common. Airborne transmission was efficient, although transmission of

  7. Delineating morbillivirus entry, dissemination and airborne transmission by studying in vivo competition of multicolor canine distemper viruses in ferrets.

    Directory of Open Access Journals (Sweden)

    Rory D de Vries

    2017-05-01

    Full Text Available Identification of cellular receptors and characterization of viral tropism in animal models have vastly improved our understanding of morbillivirus pathogenesis. However, specific aspects of viral entry, dissemination and transmission remain difficult to recapitulate in animal models. Here, we used three virologically identical but phenotypically distinct recombinant (r canine distemper viruses (CDV expressing different fluorescent reporter proteins for in vivo competition and airborne transmission studies in ferrets (Mustela putorius furo. Six donor ferrets simultaneously received three rCDVs expressing green, red or blue fluorescent proteins via conjunctival (ocular, Oc, intra-nasal (IN or intra-tracheal (IT inoculation. Two days post-inoculation sentinel ferrets were placed in physically separated adjacent cages to assess airborne transmission. All donor ferrets developed lymphopenia, fever and lethargy, showed progressively increasing systemic viral loads and were euthanized 14 to 16 days post-inoculation. Systemic replication of virus inoculated via the Oc, IN and IT routes was detected in 2/6, 5/6 and 6/6 ferrets, respectively. In five donor ferrets the IT delivered virus dominated, although replication of two or three different viruses was detected in 5/6 animals. Single lymphocytes expressing multiple fluorescent proteins were abundant in peripheral blood and lymphoid tissues, demonstrating the occurrence of double and triple virus infections. Transmission occurred efficiently and all recipient ferrets showed evidence of infection between 18 and 22 days post-inoculation of the donor ferrets. In all cases, airborne transmission resulted in replication of a single-colored virus, which was the dominant virus in the donor ferret. This study demonstrates that morbilliviruses can use multiple entry routes in parallel, and co-infection of cells during viral dissemination in the host is common. Airborne transmission was efficient, although

  8. The vectorial release of nascent immunoglobulin peptides.

    Science.gov (United States)

    Bevan, M J

    1971-03-01

    A microsomal preparation from a mouse plasmacytoma, MOPC 47A, that secretes immunoglobulin A was used to study the release of nascent immunoglobulin peptides in vitro. Nascent chains were released with puromycin and characterized with specific antiserum against the immunoglobulin product of the tumour. When the tissue had been prelabelled with [(3)H]leucine the experiments were complicated by the large background of completed radioactive polypeptides in the microsomal preparation. Up to one-third of the released radioactivity in the microsomal preparation could be recognized as immunoglobulin. With [(3)H]-puromycin as the radioactive label, however, the results are much easier to interpret, although the proportion of released radioactivity that can be identified as immunoglobulin is lower (up to one-tenth). Both types of experiment demonstrate that all of the recognizable nascent immunoglobulin chains remain in association with the microsomal vesicles after release from the ribosomes.

  9. Radioimmunoassay to quantitatively measure cell surface immunoglobulins

    International Nuclear Information System (INIS)

    Krishman, E.C.; Jewell, W.R.

    1975-01-01

    A radioimmunoassay techniques developed to quantitatively measure the presence of immunoglobulins on the surface of cells, is described. The amount of immunoglobulins found on different tumor cells varied from 200 to 1140 ng/10 6 cells. Determination of immunoglobulins on the peripheral lymphocytes obtained from different cancer patients varied between 340 to 1040 ng/10 6 cells. Cultured tumor cells, on the other hand, were found to contain negligible quantities of human IgG [pt

  10. Cytological analysis of bronchoalveolar lavage fluid acquired by bronchoscopy in healthy ferrets: A pilot study.

    Science.gov (United States)

    Bercier, Marjorie; Langlois, Isabelle; Dunn, Marilyn; Hélie, Pierre; Burns, Patrick; Gara-Boivin, Carolyn

    2016-01-01

    The objective of this study was to investigate the normal cytological evaluation of bronchoalveolar lavage (BAL) fluid in healthy adult ferrets (N = 12). These ferrets underwent bronchoscopy and BAL using sterile saline [1.5 mL/kg body weight (BW)]. Percentage of fluid recovered, total leukocyte count, differential leukocyte count, and cell count of the epithelial lining fluid (ELF) were determined. The mean percentage of lavage volume recovered from the right lung and left lung were 67.8 ± 14.9% and 69.7 ± 20.0%, respectively. Gender (P = 0.12) and weight (P = 0.17) did not significantly affect the mean percentage of recovered volume. The mean percentage of recovered volume (P = 0.47) and the mean leukocyte count (P = 0.17) from the right and left lung were not significantly different. Macrophages were the main leukocyte component of the lavages, followed by neutrophils, lymphocytes, and eosinophils. The mean proportion of ELF in BAL fluid was 9.3 ± 3.7% v/v. Bronchoscopy is clinically useful for collecting good quality BAL samples for cytological analysis in ferrets. The leucocyte differential was established, which may help veterinarians to make better clinical decisions when treating respiratory disease. Further studies are required with a larger group in order to establish the healthy reference intervals for BAL values in ferrets.

  11. A case of advanced second-degree atrioventricular block in a ferret ...

    African Journals Online (AJOL)

    admin

    2016-04-15

    Apr 15, 2016 ... Introduction. Acquired heart disease is common in ferrets over four years of age. A recent retrospective study showed that the most common echocardiographic abnormality in this species is valvular regurgitation (52%), often affecting the aortic and mitral valves (Laniesse et al.,. 2014). Left ventricle ...

  12. Cell type-specific expression of FoxP2 in the ferret and mouse retina.

    Science.gov (United States)

    Sato, Chihiro; Iwai-Takekoshi, Lena; Ichikawa, Yoshie; Kawasaki, Hiroshi

    2017-04-01

    Although the anatomical and physiological properties of subtypes of retinal ganglion cells (RGCs) have been extensively investigated, their molecular properties are still unclear. Here, we examined the expression patterns of FoxP2 in the retina of ferrets and mice. We found that FoxP2 was expressed in small subsets of neurons in the adult ferret retina. FoxP2-positive neurons in the ganglion cell layer were divided into two groups. Large FoxP2-positive neurons expressed Brn3a and were retrogradely labeled with cholera toxin subunit B injected into the optic nerve, indicating that they are RGCs. The soma size and the projection pattern of FoxP2-positive RGCs were consistent with those of X cells. Because we previously reported that FoxP2 was selectively expressed in X cells in the ferret lateral geniculate nucleus (LGN), our findings indicate that FoxP2 is specifically expressed in the parvocellular pathway from the retina to the LGN. Small FoxP2-positive neurons were positive for GAD65/67, suggesting that they are GABAergic amacrine cells. Most Foxp2-positive cells were RGCs in the adult mouse retina. Dendritic morphological analyses suggested that Foxp2-positive RGCs included direction-selective RGCs in mice. Thus, our findings suggest that FoxP2 is expressed in specific subtypes of RGCs in the retina of ferrets and mice. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  13. Using the ferret as an animal model for investigating influenza antiviral effectiveness

    Directory of Open Access Journals (Sweden)

    Ding Yuan Oh

    2016-02-01

    Full Text Available The concern of the emergence of a pandemic influenza virus has sparked an increased effort towards the development and testing of novel influenza antivirals. Central to this is the animal model of influenza infection, which has played an important role in understanding treatment effectiveness and the effect of antivirals on host immune responses. Among the different animal models of influenza, ferrets can be considered the most suitable for antiviral studies as they display most of the human-like symptoms following influenza infections, they can be infected with human influenza virus without prior viral adaptation and have the ability to transmit influenza virus efficiently between one another. However, an accurate assessment of the effectiveness of an antiviral treatment in ferrets is dependent on three major experimental considerations encompassing firstly, the volume and titre of virus, and the route of viral inoculation. Secondly, the route and dose of drug administration, and lastly, the different methods used to assess clinical symptoms, viral shedding kinetics and host immune responses in the ferrets. A good understanding of these areas is necessary to achieve data that can accurately inform the human use of influenza antivirals. In this review, we discuss the current progress and the challenges faced in these three major areas when using the ferret model to measure influenza antiviral effectiveness.

  14. De-novo transcriptome sequencing of a normalized cDNA pool from influenza infected ferrets.

    Directory of Open Access Journals (Sweden)

    Jeremy V Camp

    Full Text Available The ferret is commonly used as a model for studies of infectious diseases. The genomic sequence of this animal model is not yet characterized, and only a limited number of fully annotated cDNAs are currently available in GenBank. The majority of genes involved in innate or adaptive immune response are still lacking, restricting molecular genetic analysis of host response in the ferret model. To enable de novo identification of transcriptionally active ferret genes in response to infection, we performed de-novo transcriptome sequencing of animals infected with H1N1 A/California/07/2009. We also included splenocytes induced with bacterial lipopolysaccharide to allow for identification of transcripts specifically induced by gram-negative bacteria. We pooled and normalized the cDNA library in order to delimit the risk of sequencing only highly expressed genes. While normalization of the cDNA library removes the possibility of assessing expression changes between individual animals, it has been shown to increase identification of low abundant transcripts. In this study, we identified more than 19,000 partial ferret transcripts, including more than 1000 gene orthologs known to be involved in the innate and the adaptive immune response.

  15. Meloxicam pharmacokinetics using nonlinear mixed-effects modeling in ferrets after single subcutaneous administration.

    Science.gov (United States)

    Chinnadurai, S K; Messenger, K M; Papich, M G; Harms, C A

    2014-08-01

    This study was designed to investigate the pharmacokinetics of meloxicam, an oxicam class, nonsteroidal anti-inflammatory drug (NSAID), in ferrets. We determined the pharmacokinetic properties of a single subcutaneous dose of meloxicam (0.2 mg/kg) in nine male and nine female ferrets. Blood samples were collected by venipuncture of the cranial vena cava into heparinized syringes. Plasma meloxicam concentrations were determined by high-pressure liquid chromatography (HPLC). Pharmacokinetic variables were calculated using nonlinear mixed-effects modeling to take advantage of the population-based sampling scheme and to minimize sample volume collected per animal. Maximum plasma concentration, volume of distribution per absorption, and elimination half-life were 0.663 μg/mL, 0.21 L, and 11.4 h, respectively, for females and 0.920 μg/mL, 0.35 L, and 17.8 h, respectively, for males. Significant differences were found in each of the above parameters between male and female ferrets. Systemic clearance per absorption was not affected by gender and was 13.4 mL/h. Analgesic efficacy was not evaluated, but plasma meloxicam concentrations achieved in these animals are considered effective in other species. Sex differences in the pharmacokinetic behavior of meloxicam should be taken into consideration when treating ferrets. © 2014 John Wiley & Sons Ltd.

  16. Cytokine production by cells in cerebrospinal fluid during experimental allergic encephalomyelitis in SJL/J mice

    DEFF Research Database (Denmark)

    Renno, T; Lin, J Y; Piccirillo, C

    1994-01-01

    progression with infiltration by memory/effector CD4+ T cells, the major source of these cytokines. This cytokine upregulation was specific to the CNS, since other organs from the same animals did not express significant levels of IL-2 and IFN-gamma. CSF was obtained from the cisterna magna of unperfused mice...... and verified as such by absence of red blood cells (RBCs) and by immunoglobulin concentration orders of magnitude lower than in serum. Cytokine message was measured in RNA isolated from cells in CSF. Levels of IL-2 and IFN-gamma mRNA in CSF cells were significantly elevated in mild EAE and strongly upregulated...

  17. The Nature of Exposure Drives Transmission of Nipah Viruses from Malaysia and Bangladesh in Ferrets.

    Directory of Open Access Journals (Sweden)

    Bronwyn A Clayton

    2016-06-01

    Full Text Available Person-to-person transmission is a key feature of human Nipah virus outbreaks in Bangladesh. In contrast, in an outbreak of Nipah virus in Malaysia, people acquired infections from pigs. It is not known whether this important epidemiological difference is driven primarily by differences between NiV Bangladesh (NiV-BD and Malaysia (NiV-MY at a virus level, or by environmental or host factors. In a time course study, ferrets were oronasally exposed to equivalent doses of NiV-BD or NiV-MY. More rapid onset of productive infection and higher levels of virus replication in respiratory tract tissues were seen for NiV-BD compared to NiV-MY, corroborating our previous report of increased oral shedding of NiV-BD in ferrets and suggesting a contributory mechanism for increased NiV-BD transmission between people compared to NiV-MY. However, we recognize that transmission occurs within a social and environmental framework that may have an important and differentiating role in NiV transmission rates. With this in mind, ferret-to-ferret transmission of NiV-BD and NiV-MY was assessed under differing viral exposure conditions. Transmission was not identified for either virus when naïve ferrets were cohoused with experimentally-infected animals. In contrast, all naïve ferrets developed acute infection following assisted and direct exposure to oronasal fluid from animals that were shedding either NiV-BD or NiV-MY. Our findings for ferrets indicate that, although NiV-BD may be shed at higher levels than NiV-MY, transmission risk may be equivalently low under exposure conditions provided by cohabitation alone. In contrast, active transfer of infected bodily fluids consistently results in transmission, regardless of the virus strain. These observations suggest that the risk of NiV transmission is underpinned by social and environmental factors, and will have practical implications for managing transmission risk during outbreaks of human disease.

  18. Monitoring of Antibodies Titre Against Canine Distemper Virus in Ferrets Vaccinated with a Live Modified Vaccine

    Directory of Open Access Journals (Sweden)

    L. Pavlačík

    2007-01-01

    Full Text Available A group of five ferrets vaccinated against the canine distemper virus (CDV was evaluated as to the onset of anti-CDV antibody production and the serum levels of the animals were monitored for one year. The ferrets were immunized with a live attenuated vaccine. The vaccination pattern was as follows: primary vaccination at the age of 6 weeks, fi rst revaccination at 30 days after primary vaccination, and second revaccination after another 30 days. Blood samples were taken prior to primary vaccination and then at 30-day intervals (sampling 1 to 12. The whole experimental cycle covered the period of one year from primary vaccination (till the age of 1 year and 6 weeks. Serum samples were analysed for anti-CDV virus-neutralisation antibodies using a virus-neutralisation test using the Onderstepoort CDV strain. All ferrets had zero virus-neutralisation antibody titres before primary vaccination. Two ferrets produced virus-neutralisation antibodies as a response to first revaccination. A stable antibody level (titre 256 was maintained between months 4 and 11 after primary vaccination and a sudden increase in antibody titre (titres 512 and 1024 - 2048 occurred in both animals in months 11 and 12. The reason for the abrupt rise in antibody titres in the two animals remains unclear. No anti-CDV seroconversion was observed in the three remaining animals. Regarding the results obtained in this study we do not consider commonly recommended vaccination with a live attenuated anti-CDV vaccine as an effective method of antibodies induction against distemper in young ferrets.

  19. Cytokines in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Vinberg, Maj; Vedel Kessing, Lars

    2012-01-01

    to affective state. METHODS: We conducted a systemtic review of studies measuring endogenous cytokine concentrations in patients with bipolar disorder and a meta-analysis, reporting results according to the PRISMA statement. RESULTS: Thirteen studies were included, comprising 556 bipolar disorder patients......BACKGROUND: Current research and hypothesis regarding the pathophysiology of bipolar disorder suggests the involvement of immune system dysfunction that is possibly related to disease activity. Our objective was to systematically review evidence of cytokine alterations in bipolar disorder according...

  20. Amniotic fluid inflammatory cytokines

    DEFF Research Database (Denmark)

    Abdallah, Morsi; Larsen, Nanna; Grove, Jakob

    2013-01-01

    The aim of the study was to analyze cytokine profiles in amniotic fluid (AF) samples of children developing autism spectrum disorders (ASD) and controls, adjusting for maternal autoimmune disorders and maternal infections during pregnancy.......The aim of the study was to analyze cytokine profiles in amniotic fluid (AF) samples of children developing autism spectrum disorders (ASD) and controls, adjusting for maternal autoimmune disorders and maternal infections during pregnancy....

  1. Censored correlated cytokine concentrations

    DEFF Research Database (Denmark)

    Andersen, Andreas; Benn, Christine Stabell; Jørgensen, Mathias J

    2013-01-01

    Interest in cytokines as markers for the function of the immune system is increasing. Methods quantifying cytokine concentrations are often subject to detection limits, which lead to non-detectable observations and censored distributions. When distributions are skewed, geometric mean ratios (GMRs...... stacking method that uses clustered variance-covariance estimation allowing homogeneous (Stackc) or inhomogeneous (Stackh) variances. We compare it with direct estimation of the bivariate Tobit likelihood function (Bitobit) and multiple imputation. We assess sensitivity to inhomogeneity and non...

  2. Chylous ascites associated with abdominal trauma and intestinal resection-anastomosis in a pet ferret (Mustela putorius furo).

    Science.gov (United States)

    Chassang, Lucile; Langlois, Isabelle; Loos, Pauline; Freire, Mila; O'Toole, Elizabeth

    2018-05-15

    CASE DESCRIPTION A 10-week-old 0.73-kg (1.6-lb) castrated male domestic ferret (Mustela putorius furo) was referred for exploratory laparotomy because of pneumoperitoneum and possible septic peritonitis after being bitten by the owner's dog. CLINICAL FINDINGS Abdominal exploration revealed a large laceration of the duodenum, tears of the jejunal mesentery, and 2 small tears in the abdominal wall. Chylous abdominal effusion developed 48 hours after surgery. TREATMENT AND OUTCOME Postoperative care included supportive treatment, analgesia, and antimicrobials. An abdominal drain was placed during the laparotomy and enabled monitoring of abdominal fluid production. Enteral feeding was provided through an esophagostomy tube. The chylous fluid production rapidly decreased after treatment with octreotide was initiated, and the ferret improved. Chyloabdomen resolved after 8 days of hospitalization and medical treatment. CLINICAL RELEVANCE Findings suggested that chylous ascites can potentially develop secondary to blunt abdominal trauma in ferrets. In this ferret, chyloabdomen was successfully treated with octreotide administration and abdominal drainage.

  3. The comparison of pathology in ferrets infected by H9N2 avian influenza viruses with different genomic features.

    Science.gov (United States)

    Gao, Rongbao; Bai, Tian; Li, Xiaodan; Xiong, Ying; Huang, Yiwei; Pan, Ming; Zhang, Ye; Bo, Hong; Zou, Shumei; Shu, Yuelong

    2016-01-15

    H9N2 avian influenza virus circulates widely in poultry and has been responsible for sporadic human infections in several regions. Few studies have been conducted on the pathogenicity of H9N2 AIV isolates that have different genomic features. We compared the pathology induced by a novel reassortant H9N2 virus and two currently circulating H9N2 viruses that have different genomic features in ferrets. The results showed that the three viruses can induce infections with various amounts of viral shedding in ferrets. The novel H9N2 induced respiratory infection, but no pathological lesions were observed in lung tissues. The other two viruses induced mild to intermediate pathological lesions in lung tissues, although the clinical signs presented mildly in ferrets. The pathological lesions presented a diversity consistent with viral replication in ferrets. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Advanced diagnostic approaches and current medical management of insulinomas and adrenocortical disease in ferrets (Mustela putorius furo).

    Science.gov (United States)

    Chen, Sue

    2010-09-01

    Endocrine neoplasia is the most common tumor type in domestic ferrets, especially in middle-aged to older ferrets. Islet cell tumors and adrenocortical tumors constitute the major types of endocrine neoplasms. Insulinoma is a tumor that produces and releases excessive amounts of insulin. Evaluation of fasted blood glucose levels provides a quick diagnostic assessment for the detection of insulinomas. Use of glucocorticoids, diazoxide, and diet modification are some of the medical treatment options for insulinomas. Adrenocortical neoplasia in ferrets usually overproduces one or more sex hormones. Sex hormones which can result in progressive alopecia, vulvar swelling in females, and prostagomegaly in males. Abdominal ultrasonography and sex hormone assays can be used to diagnose adrenocortical neoplasms. Drugs such as leuprolide acetate, deslorelin acetate, and the hormone melatonin can be used to treat adrenocortical neoplasms in ferrets when surgery is not an option. Copyright 2010 Elsevier Inc. All rights reserved.

  5. Detection of inflammatory lesions with radiolabelled immunoglobulins

    International Nuclear Information System (INIS)

    Blok, D.; Rijksuniversiteit Leiden; Ogtrop, M. van; Arndt, J.W.; Camps, J.A.J.; Feitsma, R.I.J.; Pauwels, E.K.J.

    1990-01-01

    Previous reports on the use of radiolabelled immunoglobulins led us to undertake a pilot experiment in an animal model to investigate the potentials sodium pertechnate Tc 99m-immunoglobulin scintigraphy in the detection of infectious foci. Mice infected in one leg with staphylococcus infection in were injected with sodium pertechnote Tc 99m-immunoglobulin, albumin aggregated technetium Tc 99m or gallium citrate Ga 67. The results obtained by scintigraphy suggested a specific accumulation of radiolabelled immunoglobulin at the site of infection. Visualization of the infection and the image quality, especially the 6- and 24-h images, were clearly enhanced after the use of immunoglobulin preparations as compared with those labelled with gallium. (orig.)

  6. Cytokines cause functional and structural damage to isolated islets of Langerhans

    DEFF Research Database (Denmark)

    Mandrup-Poulsen, T; Bendtzen, K; Bendixen, G

    1985-01-01

    Cytokines are soluble, antigen non-specific, non-immunoglobulin mediators produced and secreted by blood mononuclear cells interacting in the cellular immune-response. To test the possibility that cytokines participate in the autoimmune destruction of the pancreatic beta-cells leading to insulin......-dependent diabetes mellitus, isolated human or rat islets of Langerhans were incubated for 7 days with cytokine-rich, cell-free supernatants of blood mononuclear cells from healthy human donors stimulated with or without purified protein derivative of tuberculin or phytohaemagglutinin. Glucose stimulated insulin......-release, and contents of insulin and glucagon in islets incubated with cytokine-rich supernatants were markedly reduced. This impairment of islet function was due to a cytotoxic effect of cytokine-rich supernatants as judged by disintegration of normal light-microscopic morphology....

  7. Recombinant F1-V fusion protein protects black-footed ferrets (Mustela nigripes) against virulent Yersinia pestis infection

    Science.gov (United States)

    Rocke, Tonie E.; Mencher, J.; Smith, Susan; Friedlander, A.M.; Andrews, G.P.; Baeten, L.A.

    2004-01-01

    Black-footed ferrets (Mustela nigripes) are highly susceptible to sylvatic plague, caused by the bacterium Yersinia pestis, and this disease has severely hampered efforts to restore ferrets to their historic range. A study was conducted to assess the efficacy of vaccination of black-footed ferrets against plague using a recombinant protein vaccine, designated F1-V, developed by personnel at the U.S. Army Medical Research Institute of Infectious Diseases. Seven postreproductive black-footed ferrets were immunized with the vaccine, followed by two booster immunizations on days 23 and 154; three control black-footed ferrets received a placebo. After the second immunization, antibody titers to both F1 and V antigen were found to be significantly higher in vaccinates than controls. On challenge with 7,800 colony-forming units of virulent plague by s.c. injection, the three control animals died within 3 days, but six of seven vaccinates survived with no ill effects. The seventh vaccinate died on day 8. These results indicate that black-footed ferrets can be immunized against plague induced by the s.c. route, similar to fleabite injection.

  8. Establishing the ferret as a gyrencephalic animal model of traumatic brain injury: Optimization of controlled cortical impact procedures.

    Science.gov (United States)

    Schwerin, Susan C; Hutchinson, Elizabeth B; Radomski, Kryslaine L; Ngalula, Kapinga P; Pierpaoli, Carlo M; Juliano, Sharon L

    2017-06-15

    Although rodent TBI studies provide valuable information regarding the effects of injury and recovery, an animal model with neuroanatomical characteristics closer to humans may provide a more meaningful basis for clinical translation. The ferret has a high white/gray matter ratio, gyrencephalic neocortex, and ventral hippocampal location. Furthermore, ferrets are amenable to behavioral training, have a body size compatible with pre-clinical MRI, and are cost-effective. We optimized the surgical procedure for controlled cortical impact (CCI) using 9 adult male ferrets. We used subject-specific brain/skull morphometric data from anatomical MRIs to overcome across-subject variability for lesion placement. We also reflected the temporalis muscle, closed the craniotomy, and used antibiotics. We then gathered MRI, behavioral, and immunohistochemical data from 6 additional animals using the optimized surgical protocol: 1 control, 3 mild, and 1 severely injured animals (surviving one week) and 1 moderately injured animal surviving sixteen weeks. The optimized surgical protocol resulted in consistent injury placement. Astrocytic reactivity increased with injury severity showing progressively greater numbers of astrocytes within the white matter. The density and morphological changes of microglia amplified with injury severity or time after injury. Motor and cognitive impairments scaled with injury severity. The optimized surgical methods differ from those used in the rodent, and are integral to success using a ferret model. We optimized ferret CCI surgery for consistent injury placement. The ferret is an excellent animal model to investigate pathophysiological and behavioral changes associated with TBI. Published by Elsevier B.V.

  9. Alternative Affinity Ligands for Immunoglobulins.

    Science.gov (United States)

    Kruljec, Nika; Bratkovič, Tomaž

    2017-08-16

    The demand for recombinant therapeutic antibodies and Fc-fusion proteins is expected to increase in the years to come. Hence, extensive efforts are concentrated on improving the downstream processing. In particular, the development of better-affinity chromatography matrices, supporting robust time- and cost-effective antibody purification, is warranted. With the advances in molecular design and high-throughput screening approaches from chemical and biological combinatorial libraries, novel affinity ligands representing alternatives to bacterial immunoglobulin (Ig)-binding proteins have entered the scene. Here, we review the design, development, and properties of diverse classes of alternative antibody-binding ligands, ranging from engineered versions of Ig-binding proteins, to artificial binding proteins, peptides, aptamers, and synthetic small-molecular-weight compounds. We also provide examples of applications for the novel affinity matrices in chromatography and beyond.

  10. Perspectives on Immunoglobulins in Colostrum and Milk

    Science.gov (United States)

    Hurley, Walter L.; Theil, Peter K.

    2011-01-01

    Immunoglobulins form an important component of the immunological activity found in milk and colostrum. They are central to the immunological link that occurs when the mother transfers passive immunity to the offspring. The mechanism of transfer varies among mammalian species. Cattle provide a readily available immune rich colostrum and milk in large quantities, making those secretions important potential sources of immune products that may benefit humans. Immune milk is a term used to describe a range of products of the bovine mammary gland that have been tested against several human diseases. The use of colostrum or milk as a source of immunoglobulins, whether intended for the neonate of the species producing the secretion or for a different species, can be viewed in the context of the types of immunoglobulins in the secretion, the mechanisms by which the immunoglobulins are secreted, and the mechanisms by which the neonate or adult consuming the milk then gains immunological benefit. The stability of immunoglobulins as they undergo processing in the milk, or undergo digestion in the intestine, is an additional consideration for evaluating the value of milk immunoglobulins. This review summarizes the fundamental knowledge of immunoglobulins found in colostrum, milk, and immune milk. PMID:22254105

  11. A case of advanced second-degree atrioventricular block in a ferret secondary to lymphoma

    Directory of Open Access Journals (Sweden)

    F. Menicagli

    2016-04-01

    Full Text Available A female ferret was referred as an emergency for severe respiratory distress symptoms. At presentation, the patient was listlessness, dyspnoeic, and hyper-responsive. The clinical examination evidenced dyspnea with cyanosis, altered cardiac rhythm, and hepatomegaly. Electrocardiography showed an advanced second-degree atrioventricular (AV block. The liver aspirate was diagnostic for lymphoma. The patient did not respond to supportive therapy and rapidly died. Post-mortem exams confirmed the presence of lymphoma with hepatic involvement. Moreover, a pericardial lymphocytic infiltration and a widespread myocardial nodular localization of lymphoma were evidenced as well. This condition was probably the cause of the cardiac arrhythmia. To the best of our knowledge, ours is the first report of cardiac lymphoma causing heart block in ferrets.

  12. Comparison of Digital Rectal and Microchip Transponder Thermometry in Ferrets (Mustela putorius furo).

    Science.gov (United States)

    Maxwell, Branden M; Brunell, Marla K; Olsen, Cara H; Bentzel, David E

    2016-01-01

    Body temperature is a common physiologic parameter measured in both clinical and research settings, with rectal thermometry being implied as the 'gold standard.' However, rectal thermometry usually requires physical or chemical restraint, potentially causing falsely elevated readings due to animal stress. A less stressful method may eliminate this confounding variable. The current study compared 2 types of digital rectal thermometers-a calibrated digital thermometer and a common digital thermometer-with an implantable subcutaneous transponder microchip. Microchips were implanted subcutaneously between the shoulder blades of 16 ferrets (8 male, 8 female), and temperatures were measured twice from the microchip reader and once from each of the rectal thermometers. Results demonstrated the microchip temperature readings had very good to good correlation and agreement to those from both of the rectal thermometers. This study indicates that implantable temperature-sensing microchips are a reliable alternative to rectal thermometry for monitoring body temperature in ferrets.

  13. Vaccines for Conservation: Plague, Prairie Dogs & Black-Footed Ferrets as a Case Study.

    Science.gov (United States)

    Salkeld, Daniel J

    2017-09-01

    The endangered black-footed ferret (Mustela nigripes) is affected by plague, caused by Yersinia pestis, both directly, as a cause of mortality, and indirectly, because of the impacts of plague on its prairie dog (Cynomys spp.) prey base. Recent developments in vaccines and vaccine delivery have raised the possibility of plague control in prairie dog populations, thereby protecting ferret populations. A large-scale experimental investigation across the western US shows that sylvatic plague vaccine delivered in oral baits can increase prairie dog survival. In northern Colorado, an examination of the efficacy of insecticides to control fleas and plague vaccine shows that timing and method of plague control is important, with different implications for long-term and large-scale management of Y. pestis delivery. In both cases, the studies show that ambitious field-work and cross-sectoral collaboration can provide potential solutions to difficult issues of wildlife management, conservation and disease ecology.

  14. Assessment of zoonotic potential of four European swine influenza viruses in the ferret model

    DEFF Research Database (Denmark)

    Fobian, Kristina; P. Fabrizio, Thomas; Yoon, Sun-Woo

    The reverse zoonotic events that introduced the 2009 pandemic influenza virus into swine herds have drastically increased the diversity of reassortants throughout Europe. The pandemic potential of these novel reassortments is unknown, hence necessitating enhanced surveillance of European swine......-like H1 and human-like N2 and one with pandemic H1 and swine-like N2. All viruses replicated to high viral titers in nasal wash- and nasal turbinate samples from inoculated ferrets and transmitted efficiently by direct contact. Only the H3N2 virus transmitted to naïve ferrets via respiratory droplets...... to neuraminidase inhibitors. These findings suggest that the investigated viruses have the potential to infect humans and further underline the need for continued surveillance as well as pandemic and zoonotic assessment of new influenza reassortants....

  15. Labelling of immunoglobulins with metal radionuclides

    International Nuclear Information System (INIS)

    Budsky, F.; Prokop, J.; Hradil, M.

    1989-01-01

    The general principles are briefly described of labelling immunoglobulins with metal radionuclides. Bicyclic anhydrides cDTPAA and cEDTAA were selected for experiments by the Nuclear Research Institute at Rez near Prague. The compounds show sufficient reactivity to immunoglobulins and can be stored in an evacuated dessicator with calcium chloride at laboratory temperature for an unlimited time. The procedure is described of the preparation of the two anhydrides and of their labelling with 111 In and 99m Tc. For both radionuclides, favourable results have been obtained in labelling immunoglobulins, which creates preconditions for the introduction of immunoscintigraphy in Czechoslovak nuclear medicine. (Z.M.). 3 tabs., 13 refs

  16. Immunoglobulin Replacement Therapy for Primary Immunodeficiency.

    Science.gov (United States)

    Sriaroon, Panida; Ballow, Mark

    2015-11-01

    Immunoglobulin replacement therapy has been standard treatment in patients with primary immunodeficiency diseases for the past 3 decades. The goal of therapy is to reduce serious bacterial infections in individuals with antibody function defects. Approximately one-third of patients receiving intravenous immunoglobulin treatment experience adverse reactions. Recent advances in manufacturing processes have resulted in products that are safer and better tolerated. Self-infusion by the subcutaneous route has become popular and resulted in better quality of life. This review summarizes the use of immunoglobulin therapy in primary immunodeficiency diseases including its properties, dosing, adverse effects, and different routes of administration. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Effect of intravenous immunoglobulin on pain in patients with post-polio syndrome.

    Science.gov (United States)

    Werhagen, Lars; Borg, Kristian

    2011-11-01

    Pain is a common symptom that affects quality of life in patients with post-polio syndrome. An increase in cytokine in the cerebrospinal fluid suggests that inflammation is pathophysiologically important in post-polio syndrome. Intravenous immunoglobulin might therefore be a therapeutic option. The aim of this study was to analyse the effect of intravenous immunoglobulin treatment on pain in post-polio syndrome. An uncontrolled clinical study. Patients with post-polio syndrome and pain (n = 45) underwent a neurological examination and were interviewed about pain before and 6 months after treatment with intravenous immunoglobulin. Pain intensity was measured on a visual analogue scale. The pain was classified according to the International Association for the Study of Pain criteria as neuropathic when it occurred in an area with decreased sensibility, or nociceptive when signs of inflammation and/or painful joints movements were present. After treatment 31/45 (69%) patients were improved, with a mean visual analogue scale decrease from 53 to 42 (p = 0.001). Eighteen patients (40%) had a decrease of 20 or more points on the visual analogue scale. The effect of treatment did not differ regarding age, gender and severity of disability. Two-thirds of 45 patients with post-polio syndrome and pain reported a decrease on the visual analogue scale for pain after treatment with intravenous immunoglobulin, and 40% reported a decrease of 20 or more points on the visual analogue scale.

  18. IMMUNOGLOBULINS IN COLOSTRUM OF SOWS WITH PORCINE REPRODUCTIVE AND RESPIRATORY SYNDROME - PRRS

    Directory of Open Access Journals (Sweden)

    Michal ROLINEC

    2012-06-01

    Full Text Available The aim of this study was to examine the effect of PRRS occurrence on sow colostrum immunological quality. We realised the experiment on 20 sows (breed: Large white. From farm without presences of PRRS were 10 sows and other 10 sows were from farm with presence of PRRS. We took the samples of sows colostrums during sucking. We detected concentration of immunoglobulins (IgG, IgA, IgM in sows colostrum in time of 0 hours to 12 hours after beginning of farrowing with pig Ig ELISA quantitation kits. We determined statistically significant (P<0.01 higher concentration of IgG at the beginning of farrowing, 3 hours, 6 hours and 12 hours from beginning of farrowing in favour of farm without presence of PRRS. We determined statistically significant (P<0.01 higher concentration of IgA at 6 and 12 hours from beginning of farrowing in favour of farm without presence of PRRS. We determined statistically significant (P<0.01 higher concentration of IgM at 6 and 12 hours from beginning of farrowing in favour of farm without presence of PRRS. Lower concentrations of colostral immunoglobulins in group with PRRS can be caused of presence of PRRS. Virus PRRS can evocate synthesis of cytokine IL-10, which inhibited the function of macrophages and lymphocytes and so PRRS decrease the production of immunoglobulins and their concentration in blood of sows and consequently also concentration of immunoglobulins in sows colostrum.

  19. Exhaled aerosol transmission of pandemic and seasonal H1N1 influenza viruses in the ferret.

    Directory of Open Access Journals (Sweden)

    Frederick Koster

    Full Text Available Person-to-person transmission of influenza viruses occurs by contact (direct and fomites and non-contact (droplet and small particle aerosol routes, but the quantitative dynamics and relative contributions of these routes are incompletely understood. The transmissibility of influenza strains estimated from secondary attack rates in closed human populations is confounded by large variations in population susceptibilities. An experimental method to phenotype strains for transmissibility in an animal model could provide relative efficiencies of transmission. We developed an experimental method to detect exhaled viral aerosol transmission between unanesthetized infected and susceptible ferrets, measured aerosol particle size and number, and quantified the viral genomic RNA in the exhaled aerosol. During brief 3-hour exposures to exhaled viral aerosols in airflow-controlled chambers, three strains of pandemic 2009 H1N1 strains were frequently transmitted to susceptible ferrets. In contrast one seasonal H1N1 strain was not transmitted in spite of higher levels of viral RNA in the exhaled aerosol. Among three pandemic strains, the two strains causing weight loss and illness in the intranasally infected 'donor' ferrets were transmitted less efficiently from the donor than the strain causing no detectable illness, suggesting that the mucosal inflammatory response may attenuate viable exhaled virus. Although exhaled viral RNA remained constant, transmission efficiency diminished from day 1 to day 5 after donor infection. Thus, aerosol transmission between ferrets may be dependent on at least four characteristics of virus-host relationships including the level of exhaled virus, infectious particle size, mucosal inflammation, and viral replication efficiency in susceptible mucosa.

  20. Replication and transmission of H9N2 influenza viruses in ferrets: evaluation of pandemic potential.

    Directory of Open Access Journals (Sweden)

    Hongquan Wan

    2008-08-01

    Full Text Available H9N2 avian influenza A viruses are endemic in poultry of many Eurasian countries and have caused repeated human infections in Asia since 1998. To evaluate the potential threat of H9N2 viruses to humans, we investigated the replication and transmission efficiency of H9N2 viruses in the ferret model. Five wild-type (WT H9N2 viruses, isolated from different avian species from 1988 through 2003, were tested in vivo and found to replicate in ferrets. However these viruses achieved mild peak viral titers in nasal washes when compared to those observed with a human H3N2 virus. Two of these H9N2 viruses transmitted to direct contact ferrets, however no aerosol transmission was detected in the virus displaying the most efficient direct contact transmission. A leucine (Leu residue at amino acid position 226 in the hemagglutinin (HA receptor-binding site (RBS, responsible for human virus-like receptor specificity, was found to be important for the transmission of the H9N2 viruses in ferrets. In addition, an H9N2 avian-human reassortant virus, which contains the surface glycoprotein genes from an H9N2 virus and the six internal genes of a human H3N2 virus, showed enhanced replication and efficient transmission to direct contacts. Although no aerosol transmission was observed, the virus replicated in multiple respiratory tissues and induced clinical signs similar to those observed with the parental human H3N2 virus. Our results suggest that the establishment and prevalence of H9N2 viruses in poultry pose a significant threat for humans.

  1. Influenza A (H10N7 Virus Causes Respiratory Tract Disease in Harbor Seals and Ferrets.

    Directory of Open Access Journals (Sweden)

    Judith M A van den Brand

    Full Text Available Avian influenza viruses sporadically cross the species barrier to mammals, including humans, in which they may cause epidemic disease. Recently such an epidemic occurred due to the emergence of avian influenza virus of the subtype H10N7 (Seal/H10N7 in harbor seals (Phoca vitulina. This epidemic caused high mortality in seals along the north-west coast of Europe and represented a potential risk for human health. To characterize the spectrum of lesions and to identify the target cells and viral distribution, findings in 16 harbor seals spontaneously infected with Seal/H10N7 are described. The seals had respiratory tract inflammation extending from the nasal cavity to bronchi associated with intralesional virus antigen in respiratory epithelial cells. Virus infection was restricted to the respiratory tract. The fatal outcome of the viral infection in seals was most likely caused by secondary bacterial infections. To investigate the pathogenic potential of H10N7 infection for humans, we inoculated the seal virus intratracheally into six ferrets and performed pathological and virological analyses at 3 and 7 days post inoculation. These experimentally inoculated ferrets displayed mild clinical signs, virus excretion from the pharynx and respiratory tract inflammation extending from bronchi to alveoli that was associated with virus antigen expression exclusively in the respiratory epithelium. Virus was isolated only from the respiratory tract. In conclusion, Seal/H10N7 infection in naturally infected harbor seals and experimentally infected ferrets shows that respiratory epithelial cells are the permissive cells for viral replication. Fatal outcome in seals was caused by secondary bacterial pneumonia similar to that in fatal human cases during influenza pandemics. Productive infection of ferrets indicates that seal/H10N7 may possess a zoonotic potential. This outbreak of LPAI from wild birds to seals demonstrates the risk of such occasions for mammals

  2. Reduced subventricular zone proliferation and white matter damage in juvenile ferrets with kaolin-induced hydrocephalus.

    Science.gov (United States)

    Di Curzio, Domenico L; Buist, Richard J; Del Bigio, Marc R

    2013-10-01

    Hydrocephalus is a neurological condition characterized by altered cerebrospinal fluid (CSF) flow with enlargement of ventricular cavities in the brain. A reliable model of hydrocephalus in gyrencephalic mammals is necessary to test preclinical hypotheses. Our objective was to characterize the behavioral, structural, and histological changes in juvenile ferrets following induction of hydrocephalus. Fourteen-day old ferrets were given an injection of kaolin (aluminum silicate) into the cisterna magna. Two days later and repeated weekly until 56 days of age, magnetic resonance (MR) imaging was used to assess ventricle size. Behavior was examined thrice weekly. Compared to age-matched saline-injected controls, severely hydrocephalic ferrets weighed significantly less, their postures were impaired, and they were hyperactive prior to extreme debilitation. They developed significant ventriculomegaly and displayed white matter destruction. Reactive astroglia and microglia detected by glial fibrillary acidic protein (GFAP) and Iba-1 immunostaining were apparent in white matter, cortex, and hippocampus. There was a hydrocephalus-related increase in activated caspase 3 labeling of apoptotic cells (7.0 vs. 15.5%) and a reduction in Ki67 labeling of proliferating cells (23.3 vs. 5.9%) in the subventricular zone (SVZ). Reduced Olig2 immunolabeling suggests a depletion of glial precursors. GFAP content was elevated. Myelin basic protein (MBP) quantitation and myelin biochemical enzyme activity showed early maturational increases. Where white matter was not destroyed, the remaining axons developed myelin similar to the controls. In conclusion, the hydrocephalus-induced periventricular disturbances may involve developmental impairments in cell proliferation and glial precursor cell populations. The ferret should prove useful for testing hypotheses about white matter damage and protection in the immature hydrocephalic brain. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Sylvatic plague vaccine: combating plague in prarie dogs and black-footed ferrets

    Science.gov (United States)

    Rocke, Tonie E.; Abbott, Rachel C.

    2012-01-01

    After achieving promising results in laboratory trials, researchers at the USGS National Wildlife Health Center (NWHC) and University of Wisconsin at Madison will soon begin field testing a new oral vaccine for sylvatic plague, a devastating disease affecting prairie dogs and other mammals, particularly the endangered black-footed ferret. Our team has developed and is currently registering a sylvatic plague vaccine (SPV) that uses raccoon poxvirus (RCN) to express two key antigens of the Yersinia pestis bacterium, the causative agent of plague.

  4. Regeneration of the vagus nerve after highly selective vagotomy, an autoradiographic study in the ferret stomach .

    OpenAIRE

    Al Muhtaseb, M. H. [محمد هاشم المحتسب; Abu-Khalaf, M.

    1995-01-01

    This study investigates the regeneration of the vagal nerve fibres after highly selective vagotomy in the ferret stomach by using the autoradiographic technique. Autoradiographic examination of the body of the stomach in the acute experimental animals has failed to show any labelled nerve fibres after highly selective vagotomy while the pylorus has shown many labelled nerve fibres . These observations indicate that the highly selective vagotomy has been performed properly and adequately. ...

  5. Cytokiner og osteoporose

    DEFF Research Database (Denmark)

    Jørgensen, N R

    1997-01-01

    During the last few years, progress has been made towards the understanding of local regulation of bone remodelling especially in relation to osteoporosis. Cytokines have shown to be powerful regulators of bone resorption and formation, though under superior control from oestrogen/testosterone, p...

  6. Recombinant Cytokines from Plants

    Czech Academy of Sciences Publication Activity Database

    Sirko, A.; Vaněk, Tomáš; Gora-Sochacka, A.; Redkiewicz, P.

    2011-01-01

    Roč. 12, č. 6 (2011), s. 3536-3552 ISSN 1661-6596 Institutional research plan: CEZ:AV0Z50380511 Keywords : cytokines * pharmaceutical proteins * plant-based production systems Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.598, year: 2011

  7. Cytokines in human milk.

    Science.gov (United States)

    Garofalo, Roberto

    2010-02-01

    Epidemiologic studies conducted in the past 30 years to investigate the protective functions of human milk strongly support the notion that breastfeeding prevents infantile infections, particularly those affecting the gastrointestinal and respiratory tracts. However, more recent clinical and experimental observations also suggest that human milk not only provides passive protection, but also can directly modulate the immunological development of the recipient infant. The study of this remarkable defense system in human milk has been difficult because of its biochemical complexity, the small concentration of certain bioactive components, the compartmentalization of some of these agents, the dynamic quantitative and qualitative changes of milk during lactation, and the lack of specific reagents to quantify these agents. However, a host of bioactive substances, including hormones, growth factors, and immunological factors such as cytokines, have been identified in human milk. Cytokines are pluripotent polypeptides that act in autocrine/paracrine fashions by binding to specific cellular receptors. They operate in networks and orchestrate the development and functions of immune system. Several different cytokines and chemokines have been discovered in human milk in the past years, and the list is growing very rapidly. This article will review the current knowledge about the increasingly complex network of chemoattractants, activators, and anti-inflammatory cytokines present in human milk and their potential role in compensating for the developmental delay of the neonate immune system. Copyright 2010. Published by Mosby, Inc.

  8. Cytokiner og osteoporose

    DEFF Research Database (Denmark)

    Jørgensen, N R

    1997-01-01

    /testosterone, parathyroidhormone and 1,25(OH)2D3. Some of the cytokines primarily enhance osteoclastic bone resorption e.g. IL-1 (Interleukin-1), TNF (Tumor Necrosis Factor) and IL-6 (Interleukin-6), while others primarily stimulate bone formation e.g. TGF-beta (Transforming Growth Factor), IGF (Insulin-like Growth Factor...

  9. Safety, efficacy and immunogenicity evaluation of the SAG2 oral rabies vaccine in Formosan ferret badgers.

    Science.gov (United States)

    Hsu, Ai-Ping; Tseng, Chun-Hsien; Barrat, Jacques; Lee, Shu-Hwae; Shih, Yu-Hua; Wasniewski, Marine; Mähl, Philippe; Chang, Chia-Chia; Lin, Chun-Ta; Chen, Re-Shang; Tu, Wen-Jane; Cliquet, Florence; Tsai, Hsiang-Jung

    2017-01-01

    Since 2013, rabies cases have been reported among Formosan ferret badgers in Taiwan, and they have been shown to be the major reservoirs for Taiwanese enzootics. To control and eradicate rabies, the authorities plan to implement a vaccination programme. Before distributing live vaccines in the field, this study assessed the safety, efficacy, and immunogenicity of SAG2 vaccine on ferret badgers by direct oral instillation. After application of 109 TCID50/dose, no virus was excreted into the oral cavity 1-7 days post-application, and safety was also satisfactorily verified over a 266-day period. Moreover, despite the low level of rabies virus neutralising antibodies induced after vaccination of a 108 TCID50/dose, the efficacy assessment revealed a 100% survival rate (15/15) of vaccinees and an 87.5% fatality rate (7/8) in control animals after a challenge on the 198th day post-vaccination. The immunisation and protection rates obtained more than 6 months after a single vaccination dose demonstrated that SAG2 is an ideal vaccine candidate to protect Formosan ferret badgers against rabies in Taiwan.

  10. Viremia associated with fatal outcomes in ferrets infected with avian H5N1 influenza virus.

    Directory of Open Access Journals (Sweden)

    Xue Wang

    Full Text Available Avian H5N1 influenza viruses cause severe disease and high mortality in infected humans. However, tissue tropism and underlying pathogenesis of H5N1 virus infection in humans needs further investigation. The objective of this work was to study viremia, tissue tropism and disease pathogenesis of H5N1 virus infection in the susceptible ferret animal model. To evaluate the relationship of morbidity and mortality with virus loads, we performed studies in ferrets infected with the H5N1 strain A/VN/1203/04 to assess clinical signs after infection and virus load in lung, brain, ileum, nasal turbinate, nasal wash, and blood. We observed that H5N1 infection in ferrets is characterized by high virus load in the brain and and low levels in the ileum using real-time PCR. In addition, viral RNA was frequently detected in blood one or two days before death and associated with symptoms of diarrhea. Our observations further substantiate pathogenicity of H5N1 and further indicate that viremia may be a bio-marker for fatal outcomes in H5N1 infection.

  11. Derivation of gnotobiotic ferrets: perinatal diet and hand-rearing requirements.

    Science.gov (United States)

    Manning, D D; Bell, J A

    1990-01-01

    A procedure is described which has resulted in successful gnotobiotic derivation of the domestic ferret. The most critical element of this hand-rearing procedure was found to be diet, with ferret milk being required for at least the first 7 days. Puppy milk replacer was phased in during the next 10 days, and enriched cow's milk sufficed thereafter. Around-the-clock sip-feeding with fire-polished Pasteur pipettes was necessary at intervals gradually increasing from 1 to 1.5 hours at birth to 3 hours by day 21. Temperature regulation was accomplished with an electric heating pad placed eccentrically under towel bedding to provide a 30 degrees-40 degrees C gradient, along which the kits positioned themselves to their own comfort. Techniques are described for minimizing fatalities due to dehydration, milk-aspiration pneumonia, underfeeding, overfeeding, gut stasis and obstipation. Internal hemorrhage, the greatest single cause of mortality in this study, manifested at day 13 and involved all kits by day 17. Despite immediate vitamin K1 dietary supplementation, five of the seven remaining kits died of hemorrhage by day 19. Around day 50, the two surviving kits were weaned from milk to dry commercial cat and ferret diets supplemented with vitamins K, C, A, D, E and B-complex and were reared to adulthood on this diet.

  12. Safety, efficacy and immunogenicity evaluation of the SAG2 oral rabies vaccine in Formosan ferret badgers.

    Directory of Open Access Journals (Sweden)

    Ai-Ping Hsu

    Full Text Available Since 2013, rabies cases have been reported among Formosan ferret badgers in Taiwan, and they have been shown to be the major reservoirs for Taiwanese enzootics. To control and eradicate rabies, the authorities plan to implement a vaccination programme. Before distributing live vaccines in the field, this study assessed the safety, efficacy, and immunogenicity of SAG2 vaccine on ferret badgers by direct oral instillation. After application of 109 TCID50/dose, no virus was excreted into the oral cavity 1-7 days post-application, and safety was also satisfactorily verified over a 266-day period. Moreover, despite the low level of rabies virus neutralising antibodies induced after vaccination of a 108 TCID50/dose, the efficacy assessment revealed a 100% survival rate (15/15 of vaccinees and an 87.5% fatality rate (7/8 in control animals after a challenge on the 198th day post-vaccination. The immunisation and protection rates obtained more than 6 months after a single vaccination dose demonstrated that SAG2 is an ideal vaccine candidate to protect Formosan ferret badgers against rabies in Taiwan.

  13. Acute Inactivation of Primary Auditory Cortex Causes a Sound Localisation Deficit in Ferrets.

    Directory of Open Access Journals (Sweden)

    Katherine C Wood

    Full Text Available The objective of this study was to demonstrate the efficacy of acute inactivation of brain areas by cooling in the behaving ferret and to demonstrate that cooling auditory cortex produced a localisation deficit that was specific to auditory stimuli. The effect of cooling on neural activity was measured in anesthetized ferret cortex. The behavioural effect of cooling was determined in a benchmark sound localisation task in which inactivation of primary auditory cortex (A1 is known to impair performance. Cooling strongly suppressed the spontaneous and stimulus-evoked firing rates of cortical neurons when the cooling loop was held at temperatures below 10°C, and this suppression was reversed when the cortical temperature recovered. Cooling of ferret auditory cortex during behavioural testing impaired sound localisation performance, with unilateral cooling producing selective deficits in the hemifield contralateral to cooling, and bilateral cooling producing deficits on both sides of space. The deficit in sound localisation induced by inactivation of A1 was not caused by motivational or locomotor changes since inactivation of A1 did not affect localisation of visual stimuli in the same context.

  14. Analgesic effect of bupivacaine eluting porcine small intestinal submucosa (SIS) in ferrets undergoing acute abdominal hernia defect surgery.

    Science.gov (United States)

    Johnson, Brenda M; Ko, Jeff C; Hall, Paul J; Saunders, Alan T; Lantz, Gary C

    2011-05-15

    Porcine small intestinal submucosa (SIS) is used as a biological implant for abdominal wall hernia repair to facilitate wound healing and augment local tissue strength. This prospective, randomized, blinded study evaluated local pain control provided by bupivacaine adsorbed to SIS for repair of acutely created abdominal wall full thickness muscle/fascial defects in ferrets. Eighteen healthy ferrets were randomly and equally assigned to three groups: (1) SIS with bupivacaine subjected to surgery, (2) SIS with no bupivacaine subjected to surgery, and (3) anesthesia only control group. Ferrets in groups 1 and 2 were anesthetized with butorphanol and sevoflurane for the surgery. Control ferrets were anesthetized in the same fashion for the same duration without surgery. Behavior and pain were evaluated in all ferrets by behavioral observation, algometer, and palpometer measurements, and heart and respiratory rates each obtained before surgery and at various intervals for 96 h after surgery. When pain reached a predetermined threshold, buprenorphine was used as a rescue analgesic. The serum and combined tissue concentrations of bupivacaine were analyzed. Overall, the palpometer testing was better tolerated in the bupivacaine treated SIS group than by the untreated SIS group (P = 0.04). There was an observed physiologically significant difference in algometer and other palpometer readings as well as heart and respiratory rates. All ferrets in the untreated SIS group were rescued while 33% of the SIS-bupivacaine groups were rescued (P pain relief over 2-4 days with no clinical adverse effects observed in the ferrets. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Thermodynamic stability contributes to immunoglobulin specificity.

    Science.gov (United States)

    Dimitrov, Jordan D; Kaveri, Srinivas V; Lacroix-Desmazes, Sébastien

    2014-05-01

    Antigen-binding specificity of immunoglobulins is important for their function in immune defense. However, immune repertoires contain a considerable fraction of immunoglobulins with promiscuous binding behavior, the physicochemical basis of which is not well understood. Evolution of immunoglobulin specificity occurs through iterative processes of mutation and selection, referred to as affinity maturation. Recent studies reveal that some somatic mutations could compromise the thermodynamic stability of the variable regions of immunoglobulins. By integrating this observation with the wealth of data on the evolution of novel enzyme activities, we propose that antibody specificity is linked to the thermodynamic stability of the antigen-binding regions, which provides a quantitative distinction between highly specific and promiscuous antibodies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. 7th International Immunoglobulin Conference: Poster presentations.

    Science.gov (United States)

    Warnatz, K; Ballow, M; Stangel, M; Bril, V

    2014-12-01

    The pan-European survey provides useful information on the accessibility and trends of intravenous and subcutaneous immunoglobulin (IVIg/SCIg) therapy, which is used to treat primary immunodeficiency disorders (PIDs). Although immunoglobulin (Ig) therapy is the first-line treatment for PIDs, the mechanisms of action of Ig therapy may differ according to the condition it is used to treat. Moreover, intriguing presentations suggest that further investigation is required to understand more clearly both the haematological and immunoregulatory effects of therapeutic immunoglobulin. This can ultimately provide more information on optimizing Ig therapy efficacy, and establish whether individualized dosing regimens for patients will be conducive to better clinical outcomes. In addition to treating autoimmune and inflammatory conditions, there is evidence to suggest that immunoglobulins can potentially play a role in transplantation, which warrants further investigation for future use. © 2014 British Society for Immunology.

  17. Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy

    NARCIS (Netherlands)

    Eftimov, Filip; Winer, John B.; Vermeulen, Marinus; de Haan, Rob; van Schaik, Ivo N.

    2013-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) causes progressive or relapsing weakness and numbness of the limbs, developing over at least two months. Uncontrolled studies suggest that intravenous immunoglobulin (IVIg) helps. This review was first published in 2002 and has since

  18. Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy

    NARCIS (Netherlands)

    Eftimov, Filip; Winer, John B.; Vermeulen, Marinus; de Haan, Rob; van Schaik, Ivo N.

    2009-01-01

    Background Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) causes progressive or relapsing weakness and numbness of the limbs, developing over at least two months. Uncontrolled studies suggest that intravenous immunoglobulin (IVIg) helps. Objectives To review systematically the

  19. Immunoglobulin profile of Nigerian children with Plasmodium ...

    African Journals Online (AJOL)

    The immunoglobulin profiles of 126 Nigerian children infected with Plasmodium falciparum in their peripheral blood were investigated. The mean malarial parasitaemia was 4699.17 ± 3695.2 ìl. The mean immunoglobulin profile of these infected children were 2.68 ± 0.019 mg/dl for IgA, 0.031 ± 0.01 mg/dl for IgD, 1358.29 ...

  20. Conservation and divergence of immunoglobulin VH pseudogenes.

    OpenAIRE

    Cohen, J B; Givol, D

    1983-01-01

    The 12 immunoglobulin VH pseudogenes, that have been characterized to date, differ from most pseudogenes of other multigene families in two aspects: (i) they carry only one (11 cases) or at the most two (1 case) deleterious mutations and (ii) they show no evidence of increased divergence from intact VH genes. We describe here the first immunoglobulin VH pseudogene that does not have these characteristics. This pseudogene accumulated numerous deleterious mutations and diverged considerably fro...

  1. Induction of Regulatory T Cells by Intravenous Immunoglobulin: A Bridge between Adaptive and Innate Immunity.

    Science.gov (United States)

    Kaufman, Gabriel N; Massoud, Amir H; Dembele, Marieme; Yona, Madelaine; Piccirillo, Ciriaco A; Mazer, Bruce D

    2015-01-01

    Intravenous immunoglobulin (IVIg) is a polyclonal immunoglobulin G preparation with potent immunomodulatory properties. The mode of action of IVIg has been investigated in multiple disease states, with various mechanisms described to account for its benefits. Recent data indicate that IVIg increases both the number and the suppressive capacity of regulatory T cells, a subpopulation of T cells that are essential for immune homeostasis. IVIg alters dendritic cell function, cytokine and chemokine networks, and T lymphocytes, leading to development of regulatory T cells. The ability of IVIg to influence Treg induction has been shown both in animal models and in human diseases. In this review, we discuss data on the potential mechanisms contributing to the interaction between IVIg and the regulatory T-cell compartment.

  2. Structure and Function of Immunoglobulins

    Science.gov (United States)

    Schroeder, Harry W; Cavacini, Lisa

    2013-01-01

    Immunoglobulins are heterodimeric proteins composed of two heavy (H) and two light (L) chains. They can be separated functionally into variable (V) domains that binds antigens and constant (C) domains that specify effector functions such as activation of complement or binding to Fc receptors. The variable domains are created by means of a complex series of gene rearrangement events, and can then be subjected to somatic hypermutation after exposure to antigen to allow affinity maturation. Each V domain can be split into three regions of sequence variability, termed the complementarity determining regions, or CDRs, and four regions of relatively constant sequence termed the framework regions, or FRs. The three CDRs of the H chain are paired with the three CDRs of the L chain to form the antigen binding site, as classically defined. There are five main classes of heavy chain C domains. Each class defines the IgM, IgG, IgA, IgD, and IgE isotypes. IgG can be split into four subclasses, IgG1, IgG2, IgG3, and IgG4, each with its own biologic properties; and IgA can similarly be split into IgA1 and IgA2. The constant domains of the H chain can be switched to allow altered effector function while maintaining antigen specificity. PMID:20176268

  3. Serum cytokine profiles of children with human enterovirus 71-associated hand, foot, and mouth disease.

    Science.gov (United States)

    Han, Jun; Wang, Ying; Gan, Xing; Song, Juan; Sun, Peng; Dong, Xiao-Ping

    2014-08-01

    Cytokine profiles may impact the pathogenicity and severity of hand, foot, and mouth disease caused by human enterovirus (HEV) 71. In 91 severe or mild HEV 71-associated hand, foot, and mouth disease children, serum was collected between days 2 and 10 or day >10. Serum cytokines including Type 1 T helper (Th1) cytokines: interleukin (IL)-2, interferon-gamma (IFN-γ), IL-12, and IL-18, Type 1 T helper (Th2) cytokines: IL-4, IL-10, IL-13, proinflammatory cytokines: IL-1α, IL-1β, IL-6, IL-8, IL-17, and tumor necrosis factor alpha (TNF-α), were assessed during the early stage and recovery. In the patients with mild illness, the peaks of IL-8 and IL-10 were observed on day 6 and that of IL-18 was on day 4. In the patients with severe illness, all cytokines spiked on day 3 and peaked on day 11. All cytokines except IL-6, IL-8, IL-18, and TNF-α were significantly correlated with immunoglobulin M levels by the end of the disease course. Cytokine profile variations between the patients with mild and severe illness may indicate prognosis and strain virulence, useful in clinical treatment of patients. © 2014 Wiley Periodicals, Inc.

  4. Immunoglobulin E-Mediated Autoimmunity

    Directory of Open Access Journals (Sweden)

    Marcus Maurer

    2018-04-01

    Full Text Available The study of autoimmunity mediated by immunoglobulin E (IgE autoantibodies, which may be termed autoallergy, is in its infancy. It is now recognized that systemic lupus erythematosus, bullous pemphigoid (BP, and chronic urticaria, both spontaneous and inducible, are most likely to be mediated, at least in part, by IgE autoantibodies. The situation in other conditions, such as autoimmune uveitis, rheumatoid arthritis, hyperthyroid Graves’ disease, autoimmune pancreatitis, and even asthma, is far less clear but evidence for autoallergy is accumulating. To be certain of an autoallergic mechanism, it is necessary to identify both IgE autoantibodies and their targets as has been done with the transmembrane protein BP180 and the intracellular protein BP230 in BP and IL-24 in chronic spontaneous urticaria. Also, IgE-targeted therapies, such as anti-IgE, must have been shown to be of benefit to patients as has been done with both of these conditions. This comprehensive review of the literature on IgE-mediated autoallergy focuses on three related questions. What do we know about the prevalence of IgE autoantibodies and their targets in different diseases? What do we know about the relevance of IgE autoantibodies in different diseases? What do we know about the cellular and molecular effects of IgE autoantibodies? In addition to providing answers to these questions, based on a broad review of the literature, we outline the current gaps of knowledge in our understanding of IgE autoantibodies and describe approaches to address them.

  5. Detection of autoantibodies to cytokines

    DEFF Research Database (Denmark)

    Bendtzen, K; Hansen, M B; Ross, C

    2000-01-01

    Autoantibodies to various cytokines have been reported in normal individuals and in patients with various infectious and immunoinflammatory disorders, and similar antibodies (Ab) may be induced in patients receiving human recombinant cytokines. The clinical relevance of these Ab is often difficult...... to evaluate. Not only are in vitro neutralizing cytokine Ab not necessarily neutralizing in vivo, but assays for binding and neutralizing Ab to cytokines are often difficult to interpret. For example, denaturation of immobilized cytokines in immunoblotting techniques and immunometric assays may leave Ab...

  6. Cow's milk with active immunoglobulins against Campylobacter jejuni: effects of temperature on immunoglobulin activity.

    Science.gov (United States)

    Riera, Francisco; Alvarez, Alejandro; Espi, Alberto; Prieto, Miguel; de la Roza, Begoña; Vicente, Fernando

    2014-04-01

    Adult Holstein cows were injected with an antiserum against Campylobacter jejuni and immunoglobulin activities in vitro were determined in blood and milk several weeks after injection. The immunoactivity of immunoglobulins in milk was measured by an ELISA after different temperature-time treatments (60-91°C and 4-3600 s) at laboratory and pilot-plant scales. Kinetic and thermodynamic parameters were determined. An increase in immunoglobulin activity in milk was detected several days after injection. Optical densities increased by three- to seven-fold in this period. The activity started to decay 4-5 weeks after injection. Immunoglobulins maintained most of their in vitro activity under pasteurisation conditions (72°C and 15 s) and were denatured following first-order kinetics. The injection protocol applied allows milk with specific immunoglobulins against Campylobacter jejuni to be obtained. Traditional pasteurisation did not reduce this activity. © 2013 Society of Chemical Industry.

  7. Neurovirulence of H5N1 infection in ferrets is mediated by multifocal replication in distinct permissive neuronal cell regions.

    Directory of Open Access Journals (Sweden)

    Jennifer R Plourde

    Full Text Available Highly pathogenic avian influenza A (HPAI, subtype H5N1, remains an emergent threat to the human population. While respiratory disease is a hallmark of influenza infection, H5N1 has a high incidence of neurological sequelae in many animal species and sporadically in humans. We elucidate the temporal/spatial infection of H5N1 in the brain of ferrets following a low dose, intranasal infection of two HPAI strains of varying neurovirulence and lethality. A/Vietnam/1203/2004 (VN1203 induced mortality in 100% of infected ferrets while A/Hong Kong/483/1997 (HK483 induced lethality in only 20% of ferrets, with death occurring significantly later following infection. Neurological signs were prominent in VN1203 infection, but not HK483, with seizures observed three days post challenge and torticollis or paresis at later time points. VN1203 and HK483 replication kinetics were similar in primary differentiated ferret nasal turbinate cells, and similar viral titers were measured in the nasal turbinates of infected ferrets. Pulmonary viral titers were not different between strains and pathological findings in the lungs were similar in severity. VN1203 replicated to high titers in the olfactory bulb, cerebral cortex, and brain stem; whereas HK483 was not recovered in these tissues. VN1203 was identified adjacent to and within the olfactory nerve tract, and multifocal infection was observed throughout the frontal cortex and cerebrum. VN1203 was also detected throughout the cerebellum, specifically in Purkinje cells and regions that coordinate voluntary movements. These findings suggest the increased lethality of VN1203 in ferrets is due to increased replication in brain regions important in higher order function and explains the neurological signs observed during H5N1 neurovirulence.

  8. Perspectives on Immunoglobulins in colostrum and milk

    DEFF Research Database (Denmark)

    Hurley, W L; Theil, Peter Kappel

    2011-01-01

    Immunoglobulins form an important component of the immunological activity found in milk and colostrum. They are central to the immunological link that occurs when the mother transfers passive immunity to the offspring. The mechanism of transfer varies among mammalian species. Cattle provide...... a readily available immune rich colostrum and milk in large quantities, making those secretions important potential sources of immune products that may benefit humans. Immune milk is a term used to describe a range of products of the bovine mammary gland that have been tested against several human diseases......, and the mechanisms by which the neonate or adult consuming the milk then gains immunological benefit. The stability of immunoglobulins as they undergo processing in the milk, or undergo digestion in the intestine, is an additional consideration for evaluating the value of milk immunoglobulins. This review summarizes...

  9. Effects of developmental alcohol and valproic acid exposure on play behavior of ferrets.

    Science.gov (United States)

    Krahe, Thomas E; Filgueiras, Claudio C; Medina, Alexandre E

    2016-08-01

    Exposure to alcohol and valproic acid (VPA) during pregnancy can lead to fetal alcohol spectrum disorders and fetal valproate syndrome, respectively. Altered social behavior is a hallmark of both these conditions and there is ample evidence showing that developmental exposure to alcohol and VPA affect social behavior in rodents. However, results from rodent models are somewhat difficult to translate to humans owing to the substantial differences in brain development, morphology, and connectivity. Since the cortex folding pattern is closely related to its specialization and that social behavior is strongly influenced by cortical structures, here we studied the effects of developmental alcohol and VPA exposure on the play behavior of the ferret, a gyrencephalic animal known for its playful nature. Animals were injected with alcohol (3.5g/kg, i.p.), VPA (200mg/kg, i.p.) or saline (i.p) every other day during the brain growth spurt period, between postnatal days 10 and 30. The play behavior of pairs of the same experimental group was evaluated 3 weeks later. Both treatments induced significant behavioral differences compared to controls. Alcohol and VPA exposed ferrets played less than saline treated ones, but while animals from the alcohol group displayed a delay in start playing with each other, VPA treated ones spent most of the time close to one another without playing. These findings not only extend previous results on the effects of developmental exposure to alcohol and VPA on social behavior, but make the ferret a great model to study the underlying mechanisms of social interaction. Copyright © 2016. Published by Elsevier Ltd.

  10. Recombinant Hendra viruses expressing a reporter gene retain pathogenicity in ferrets.

    Science.gov (United States)

    Marsh, Glenn A; Virtue, Elena R; Smith, Ina; Todd, Shawn; Arkinstall, Rachel; Frazer, Leah; Monaghan, Paul; Smith, Greg A; Broder, Christopher C; Middleton, Deborah; Wang, Lin-Fa

    2013-03-25

    Hendra virus (HeV) is an Australian bat-borne zoonotic paramyxovirus that repeatedly spills-over to horses causing fatal disease. Human cases have all been associated with close contact with infected horses. A full-length antigenome clone of HeV was assembled, a reporter gene (GFP or luciferase) inserted between the P and M genes and transfected to 293T cells to generate infectious reporter gene-encoding recombinant viruses. These viruses were then assessed in vitro for expression of the reporter genes. The GFP expressing recombinant HeV was used to challenge ferrets to assess the virulence and tissue distribution by monitoring GFP expression in infected cells. Three recombinant HeV constructs were successfully cloned and rescued; a wild-type virus, a GFP-expressing virus and a firefly luciferase-expressing virus. In vitro characterisation demonstrated expression of the reporter genes, with levels proportional to the initial inoculum levels. Challenge of ferrets with the GFP virus demonstrated maintenance of the fatal phenotype with disease progressing to death consistent with that observed previously with the parental wild-type isolate of HeV. GFP expression could be observed in infected tissues collected from animals at euthanasia. Here, we report on the first successful rescue of recombinant HeV, including wild-type virus and viruses expressing two different reporter genes encoded as an additional gene cassette inserted between the P and M genes. We further demonstrate that the GFP virus retained the ability to cause fatal disease in a well-characterized ferret model of henipavirus infection despite the genome being an extra 1290 nucleotides in length.

  11. Pathogenicity and transmissibility of North American triple reassortant swine influenza A viruses in ferrets.

    Directory of Open Access Journals (Sweden)

    Subrata Barman

    Full Text Available North American triple reassortant swine (TRS influenza A viruses have caused sporadic human infections since 2005, but human-to-human transmission has not been documented. These viruses have six gene segments (PB2, PB1, PA, HA, NP, and NS closely related to those of the 2009 H1N1 pandemic viruses. Therefore, understanding of these viruses' pathogenicity and transmissibility may help to identify determinants of virulence of the 2009 H1N1 pandemic viruses and to elucidate potential human health threats posed by the TRS viruses. Here we evaluated in a ferret model the pathogenicity and transmissibility of three groups of North American TRS viruses containing swine-like and/or human-like HA and NA gene segments. The study was designed only to detect informative and significant patterns in the transmissibility and pathogenicity of these three groups of viruses. We observed that irrespective of their HA and NA lineages, the TRS viruses were moderately pathogenic in ferrets and grew efficiently in both the upper and lower respiratory tracts. All North American TRS viruses studied were transmitted between ferrets via direct contact. However, their transmissibility by respiratory droplets was related to their HA and NA lineages: TRS viruses with human-like HA and NA were transmitted most efficiently, those with swine-like HA and NA were transmitted minimally or not transmitted, and those with swine-like HA and human-like NA (N2 showed intermediate transmissibility. We conclude that the lineages of HA and NA may play a crucial role in the respiratory droplet transmissibility of these viruses. These findings have important implications for pandemic planning and warrant confirmation.

  12. Effects of beta-carotene supplementation on adipose tissue thermogenic capacity in ferrets (Mustela putorius furo).

    Science.gov (United States)

    Sánchez, Juana; Fuster, Antonia; Oliver, Paula; Palou, Andreu; Picó, Catalina

    2009-12-01

    We previously described that the intake of pharmacological doses of beta-carotene (BC) resulted in higher body weight gain in the ferret (Mustela putorius furo), an animal model that resembles human subjects in terms of intestinal BC absorption and metabolism. These results were some way unexpected considering the condition of BC as a vitamin A precursor and the previous data in rodents showing these compounds as thermogenic activators. Here, we aimed to characterise in the ferret whether the mentioned changes in body weight could be explained by changes in adipose tissue thermogenic capacity. We studied the effects of 6-month supplementation with BC (0.8 and 3.2 mg/kg per d) on adipose tissue morphology and uncoupling protein-1 (UCP1) content. BC supplementation resulted in higher body weight (the high dose), induced depot- and dose-dependent hypertrophy of white adipocytes, decreased the amount of brown-like multilocular adipocytes in the retroperitoneal depot and decreased UCP1 content in different fat depots. To ascertain whether BC effects could be mediated by retinoic acid (RA), 1 week supplementation with RA (0.25 and 25 mg/kg per d) was also studied. RA treatment resulted in a slight decrease in adiposity, decreased cell lipid accumulation and increased UCP1 content, suggesting that the effects of BC on thermogenic capacity are not through RA. In conclusion, RA, but not BC, may have in the ferret comparable effects with those described in rodents, whereas differences concerning BC and RA treatments may be attributable to the different BC metabolism in the present animal model with a lower conversion of BC to RA compared with rodents.

  13. Pathogenicity testing of influenza candidate vaccine viruses in the ferret model.

    Science.gov (United States)

    Belser, Jessica A; Johnson, Adam; Pulit-Penaloza, Joanna A; Pappas, Claudia; Pearce, Melissa B; Tzeng, Wen-Pin; Hossain, M Jaber; Ridenour, Callie; Wang, Li; Chen, Li-Mei; Wentworth, David E; Katz, Jacqueline M; Maines, Taronna R; Tumpey, Terrence M

    2017-11-01

    The development of influenza candidate vaccine viruses (CVVs) for pre-pandemic vaccine production represents a critical step in pandemic preparedness. The multiple subtypes and clades of avian or swine origin influenza viruses circulating world-wide at any one time necessitates the continuous generation of CVVs to provide an advanced starting point should a novel zoonotic virus cross the species barrier and cause a pandemic. Furthermore, the evolution and diversity of novel influenza viruses that cause zoonotic infections requires ongoing monitoring and surveillance, and, when a lack of antigenic match between circulating viruses and available CVVs is identified, the production of new CVVs. Pandemic guidelines developed by the WHO Global Influenza Program govern the design and preparation of reverse genetics-derived CVVs, which must undergo numerous safety and quality tests prior to human use. Confirmation of reassortant CVV attenuation of virulence in ferrets relative to wild-type virus represents one of these critical steps, yet there is a paucity of information available regarding the relative degree of attenuation achieved by WHO-recommended CVVs developed against novel viruses with pandemic potential. To better understand the degree of CVV attenuation in the ferret model, we examined the relative virulence of six A/Puerto Rico/8/1934-based CVVs encompassing five different influenza A subtypes (H2N3, H5N1, H5N2, H5N8, and H7N9) compared with the respective wild-type virus in ferrets. Despite varied virulence of wild-type viruses in the ferret, all CVVs examined showed reductions in morbidity and viral shedding in upper respiratory tract tissues. Furthermore, unlike the wild-type counterparts, none of the CVVs spread to extrapulmonary tissues during the acute phase of infection. While the magnitude of virus attenuation varied between virus subtypes, collectively we show the reliable and reproducible attenuation of CVVs that have the A/Puerto Rico/9/1934 backbone

  14. Translocations affecting human immunoglobulin heavy chain locus

    Directory of Open Access Journals (Sweden)

    Sklyar I. V.

    2014-03-01

    Full Text Available Translocations involving human immunoglobulin heavy chain (IGH locus are implicated in different leukaemias and lymphomas, including multiple myeloma, mantle cell lymphoma, Burkitt’s lymphoma and diffuse large B cell lymphoma. We have analysed published data and identified eleven breakpoint cluster regions (bcr related to these cancers within the IgH locus. These ~1 kbp bcrs are specific for one or several types of blood cancer. Our findings could help devise PCR-based assays to detect cancer-related translocations, to identify the mechanisms of translocations and to help in the research of potential translocation partners of the immunoglobulin locus at different stages of B-cell differentiation.

  15. Intravenous polyclonal human immunoglobulins in multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, Per Soelberg

    2008-01-01

    Intravenous immunoglobulin (IVIG) is an established therapy for demyelinating diseases of the peripheral nervous system. IVIG exerts a number of effects that may be beneficial in multiple sclerosis (MS). Four double-blind IVIG trials have been performed in relapsing-remitting MS. A meta-analysis ......Intravenous immunoglobulin (IVIG) is an established therapy for demyelinating diseases of the peripheral nervous system. IVIG exerts a number of effects that may be beneficial in multiple sclerosis (MS). Four double-blind IVIG trials have been performed in relapsing-remitting MS. A meta...

  16. Cytokine regulation of immune tolerance

    OpenAIRE

    Wu, Jie; Xie, Aini; Chen, Wenhao

    2014-01-01

    The immune system provides defenses against invading pathogens while maintaining immune tolerance to self-antigens. This immune homeostasis is harmonized by the direct interactions between immune cells and the cytokine environment in which immune cells develop and function. Herein, we discuss three non-redundant paradigms by which cytokines maintain or break immune tolerance. We firstly describe how anti-inflammatory cytokines exert direct inhibitory effects on immune cells to enforce immune ...

  17. Place du dosage des immunoglobulines e totales en pratique ...

    African Journals Online (AJOL)

    Mots clés: Immunoglobulines E, allergie, Togo. English Abstract. Place of total immunoglobulin E dosage in common practice in Togo. Objective: to determine the place of total immunoglobulin E (IgE) dosage in common practice in Togo. Material and methods: 650 total IgE dosages performed during 4 years (2008 to 2011) ...

  18. Class I Cytokine Receptors

    DEFF Research Database (Denmark)

    Steinocher, Helena

    , the minimal determinants for specificity between membrane spanning helices were investigated with small artificial low complexity peptides, prior found to activate the EPOR in cells. The placement of single methyl group in the so called transmembrane aptamers (traptamers) determined the stabilizing effect...... characteristics of membrane spanning helices, was designed and hGHR TMD and hEPOR TMD produced in sufficient amounts for spectroscopic investigations. The isolated hGHR TMD was revealed to associate in dimeric complexes in detergent micelles and first presumptions about the dimer interface could be made. Further...... the traptamers on the hEPOR TMD dimeric complex in detergent micelles. To gain a better understanding of hGHR regulation a point mutation in the hGHR intracellular domain (ICD), which has recently been linked to lung cancer, was characterized. The mutation was found to decrease binding of suppressor of cytokine...

  19. Treatment of multiple system atrophy using intravenous immunoglobulin

    Directory of Open Access Journals (Sweden)

    Novak Peter

    2012-11-01

    Full Text Available Abstract Background Multiple system atrophy (MSA is a progressive neurodegenerative disorder of unknown etiology, manifesting as combination of parkinsonism, cerebellar syndrome and dysautonomia. Disease-modifying therapies are unavailable. Activation of microglia and production of toxic cytokines suggest a role of neuroinflammation in MSA pathogenesis. This pilot clinical trial evaluated safety and tolerability of intravenous immunoglobulin (IVIG in MSA. Methods This was a single-arm interventional, single-center, open-label pilot study. Interventions included monthly infusions of the IVIG preparation Privigen®, dose 0.4 gram/kg, for 6 months. Primary outcome measures evaluated safety and secondary outcome measures evaluated preliminary efficacy of IVIG. Unified MSA Rating Scale (UMSARS was measured monthly. Quantitative brain imaging using 3T MRI was performed before and after treatment. Results Nine subjects were enrolled, and seven (2 women and 5 men, age range 55–64 years completed the protocol. There were no serious adverse events. Systolic blood pressure increased during IVIG infusions (p Conclusions Treatment with IVIG appears to be safe, feasible and well tolerated and may improve functionality in MSA. A larger, placebo-controlled study is needed.

  20. Intravenous immunoglobulin treatment for secondary recurrent miscarriage

    DEFF Research Database (Denmark)

    Christiansen, O B; Larsen, E C; Egerup, P

    2015-01-01

    OBJECTIVE: To determine whether infusions with intravenous immunoglobulin (IVIg) during early pregnancy increase live birth rate in women with secondary recurrent miscarriage compared with placebo. DESIGN: A single-centre, randomised, double-blind, placebo-controlled trial. SETTING: A tertiary...

  1. Immunoglobulins, antibody repertoire and B cell development

    Czech Academy of Sciences Publication Activity Database

    Butler, J. E.; Zhao, Y.; Šinkora, Marek; Wertz, N.; Kacskovics, I.

    2009-01-01

    Roč. 33, č. 3 (2009), s. 321-333 ISSN 0145-305X R&D Projects: GA ČR GA523/07/0088 Institutional research plan: CEZ:AV0Z50200510 Keywords : swine * immunoglobulin * b cell Subject RIV: EC - Immunology Impact factor: 3.290, year: 2009

  2. Ancient Phylogenetic Beginnings of Immunoglobulin Hypermutation

    Czech Academy of Sciences Publication Activity Database

    Kubrycht, J.; Sigler, Karel; Růžička, Michal; Souček, P.; Borecký, J.; Ježek, Petr

    2006-01-01

    Roč. 63, - (2006), s. 691-706 ISSN 0022-2844 Institutional research plan: CEZ:AV0Z50200510; CEZ:AV0Z50110509 Keywords : immunoglobulin * hypermutation * antigen Subject RIV: EE - Microbiology, Virology Impact factor: 2.767, year: 2006

  3. Immunoglobulin for necrotising soft tissue infections (INSTINCT)

    DEFF Research Database (Denmark)

    Madsen, Martin Bruun; Lange, Theis; Hjortrup, Peter Buhl

    2016-01-01

    INTRODUCTION: Necrotising soft tissue infections (NSTI) are aggressive infections that can result in severe disability or death. Intravenous polyspecific immunoglobulin G (IVIG) is used as supplementary treatment for patients with NSTIs. The level of evidence is very low, but suggests that IVIG may...

  4. 6th International Immunoglobulin Symposium: poster presentations

    NARCIS (Netherlands)

    Fernandez-Cruz, E.; Kaveri, S. V.; Peter, H.-H.; Durandy, A.; Cantoni, N.; Quinti, I.; Sorensen, R.; Bussel, J. B.; Danieli, M. G.; Winkelmann, A.; Bayry, J.; Käsermann, F.; Späth, P.; Helbert, M.; Salama, A.; van Schaik, I. N.; Yuki, N.

    2009-01-01

    The posters presented at the 6th International Immunoglobulin Symposium covered a wide range of fields and included both basic science and clinical research. From the abstracts accepted for poster presentation, 12 abstracts were selected for oral presentations in three parallel sessions on

  5. 6th International Immunoglobulin Symposium: Poster presentations

    NARCIS (Netherlands)

    Fernandez-Cruz, E.; Kaveri, S.V.; Peter, H.H.; Durandy, A.; Cantoni, N.; Quinti, I.; Sorensen, R.; Bussel, J.B.; Danieli, M.G.; Winkelmann, A.; Bayry, J.; Kaesermann, F.; Spaeth, P.; Helbert, M.; Salama, A.; van Schaik, I.N.; Yuki, N.

    2009-01-01

    P>The posters presented at the 6th International Immunoglobulin Symposium covered a wide range of fields and included both basic science and clinical research. From the abstracts accepted for poster presentation, 12 abstracts were selected for oral presentations in three parallel sessions on

  6. Intravenous immunoglobulin prophylaxis in neonates on artificial ...

    African Journals Online (AJOL)

    The efficacy of the prophylactic use of intravenous immunoglobulin (Ig) was evaluated in a double-blind placebo-controlled trial of 21 pairs of ventilated neonates weighing more than 1 500 g, Each infant received 0.4 g/kglday of intravenous Ig or a similar volume of placebo daily for 5 days. Criteria used to assess the ...

  7. Blood Test: Immunoglobulin A (IgA)

    Science.gov (United States)

    ... Blood Test: Immunoglobulin A (IgA) What's in this article? What It Is Why It's Done Preparation The Procedure What to Expect Getting the Results Risks Helping Your Child If You Have Questions Print en español Análisis de sangre: inmunoglobulina A (IgA) What It Is An IgA ...

  8. Immunoglobulins and their fragments on solid surfaces

    NARCIS (Netherlands)

    Buijs, J.A.G.

    1995-01-01

    Summary

    Adsorption of immunoglobulin G (IgG) is a common step in the production of immunological tests and biosensors. The use of IgG in these applications stems from its ability to specifically bind all kinds of molecules (antigens). In these tests the IgG

  9. Killer immunoglobulin receptor genes in spondyloarthritis

    NARCIS (Netherlands)

    Kuijpers, Taco W.; Vendelbosch, Sanne; van den Berg, Merlijn; Baeten, Dominique L. P.

    2016-01-01

    We focus on the role of killer immunoglobulin receptor (KIR) interactions with the human leukocyte antigens (HLA)-B27 ligand and the potential contribution of KIR-expressing natural killer and T cells in spondyloarthritis, more specifically in ankylosing spondylitis (AS). In AS strong

  10. Facilitated subcutaneous immunoglobulin administration (fSCIg)

    DEFF Research Database (Denmark)

    Blau, Igor-Wolfgang; Conlon, Niall; Petermann, Robert

    2016-01-01

    and diverse medical needs that treatments for SID management should strive to meet. In this special report, we study the opportunities provided by facilitated subcutaneous immunoglobulin administration (fSCIg) to treat patients for whom the conventional routes (intravenous and subcutaneous) are sub...

  11. Prediction of the course of acute odontogenic pathology with pronounced osteomyelitis by immunoglobulin and cytokin evaluation

    Directory of Open Access Journals (Sweden)

    A. I. Yaremenko

    2013-01-01

    Full Text Available The aim of our trial was detection of the most significant clinico-laboratory factors in the saliva and blood samples of the patients with odontogenic osteomyelitis in order to predict severity of the clinical course of osteomyelitis and to choose the optimal treatment tactics.

  12. Man's underground best friend: domestic ferrets, unlike the wild forms, show evidence of dog-like social-cognitive skills.

    Directory of Open Access Journals (Sweden)

    Anna Hernádi

    Full Text Available Recent research has shown that dogs' possess surprisingly sophisticated human-like social communication skills compared to wolves or chimpanzees. The effects of domestication on the emergence of socio-cognitive skills, however, are still highly debated. One way to investigate this is to compare socialized individuals from closely related domestic and wild species. In the present study we tested domestic ferrets (Mustela furo and compared their performance to a group of wild Mustela hybrids and to domestic dogs (Canis familiaris. We found that, in contrast to wild Mustela hybrids, both domestic ferrets and dogs tolerated eye-contact for a longer time when facing their owners versus the experimenter and they showed a preference in a two-way choice task towards their owners. Furthermore, domestic ferrets, unlike the wild hybrids, were able to follow human directional gestures (sustained touching; momentary pointing and could reach the success rate of dogs. Our study provides the first evidence that domestic ferrets, in a certain sense, are more dog-like than their wild counterparts. These findings support the hypothesis that domestic species may share basic socio-cognitive skills that enable them to engage in effectively orchestrated social interactions with humans.

  13. Man's underground best friend: domestic ferrets, unlike the wild forms, show evidence of dog-like social-cognitive skills.

    Science.gov (United States)

    Hernádi, Anna; Kis, Anna; Turcsán, Borbála; Topál, József

    2012-01-01

    Recent research has shown that dogs' possess surprisingly sophisticated human-like social communication skills compared to wolves or chimpanzees. The effects of domestication on the emergence of socio-cognitive skills, however, are still highly debated. One way to investigate this is to compare socialized individuals from closely related domestic and wild species. In the present study we tested domestic ferrets (Mustela furo) and compared their performance to a group of wild Mustela hybrids and to domestic dogs (Canis familiaris). We found that, in contrast to wild Mustela hybrids, both domestic ferrets and dogs tolerated eye-contact for a longer time when facing their owners versus the experimenter and they showed a preference in a two-way choice task towards their owners. Furthermore, domestic ferrets, unlike the wild hybrids, were able to follow human directional gestures (sustained touching; momentary pointing) and could reach the success rate of dogs. Our study provides the first evidence that domestic ferrets, in a certain sense, are more dog-like than their wild counterparts. These findings support the hypothesis that domestic species may share basic socio-cognitive skills that enable them to engage in effectively orchestrated social interactions with humans.

  14. Epidemiology and clinical presentation of canine distemper disease in dogs and ferrets in Australia, 2006-2014.

    Science.gov (United States)

    Wyllie, S E; Kelman, M; Ward, M P

    2016-07-01

    To determine the status and distribution of distemper in Australian dogs and ferrets. Retrospective case series. Cases were identified via a national voluntary disease reporting system, veterinarian groups and a national laboratory database. The geographic distribution, seasonal distribution, signalment and clinical presentation of cases were described using maps and frequency distributions. A total of 48 individually affected dogs and ferrets in 27 case groups were identified, including eight confirmed case groups (> one individual). Confirmed cases were more common in summer and on the central coast of New South Wales and southern Victoria, and occurred exclusively in young, unvaccinated dogs. For dogs there was no obvious sex predilection. A mortality rate of 100% in ferrets and up to 77% in dogs was estimated. Neurological, gastrointestinal and respiratory were the most commonly reported systems affected in dogs and ferrets. There was no evidence that any large, unreported outbreaks occurred during the study period. Continuation of vaccination against canine distemper virus is justified within Australia, particularly for younger dogs. Veterinarians should continue to consider distemper in their differential diagnosis of cases with neurological, gastrointestinal and respiratory presentation. © 2016 Australian Veterinary Association.

  15. A neutralizing human monoclonal antibody protects against lethal disease in a new ferret model of acute nipah virus infection.

    Directory of Open Access Journals (Sweden)

    Katharine N Bossart

    2009-10-01

    Full Text Available Nipah virus is a broadly tropic and highly pathogenic zoonotic paramyxovirus in the genus Henipavirus whose natural reservoirs are several species of Pteropus fruit bats. Nipah virus has repeatedly caused outbreaks over the past decade associated with a severe and often fatal disease in humans and animals. Here, a new ferret model of Nipah virus pathogenesis is described where both respiratory and neurological disease are present in infected animals. Severe disease occurs with viral doses as low as 500 TCID(50 within 6 to 10 days following infection. The underlying pathology seen in the ferret closely resembles that seen in Nipah virus infected humans, characterized as a widespread multisystemic vasculitis, with virus replicating in highly vascular tissues including lung, spleen and brain, with recoverable virus from a variety of tissues. Using this ferret model a cross-reactive neutralizing human monoclonal antibody, m102.4, targeting the henipavirus G glycoprotein was evaluated in vivo as a potential therapeutic agent. All ferrets that received m102.4 ten hours following a high dose oral-nasal Nipah virus challenge were protected from disease while all controls died. This study is the first successful post-exposure passive antibody therapy for Nipah virus using a human monoclonal antibody.

  16. Comparison of mucus flow rate, radiolabelled glycoprotein output and smooth muscle contraction in the ferret trachea in vitro

    NARCIS (Netherlands)

    Kyle, H.; Widdicombe, J.G.; Wilffert, B.

    1988-01-01

    1. The concentration-response curves for rate of mucus output, labelled-glycoprotein output and smooth muscle contraction in response to methacholine, phenylephrine and salbutamol were determined in the ferret trachea in vitro. 2. The potencies of methacholine and phenylephrine are both in order:

  17. Vaccination as a potential means to prevent plague in black-footed ferrets: Progress and continuing challenges

    Science.gov (United States)

    Rocke, Tonie E.; Nol, Pauline; Marinari, Paul E.; Kreeger, J.S.; Smith, Susan R.; Andrews, G.P.; Friedlander, A.W.

    2006-01-01

    This study was conducted to further assess the feasibility of vaccinating black-footed ferrets (Mustela nigripes) against plague (caused by the bacterium Yersinia pestis). On days 0 and 28, 17 postreproductive ferrets were immunized by subcutaneous injection with a recombinant fusion protein containing F1 and V antigens from Y. pestis. Another 17 animals received a placebo by the same route. Two weeks after the second immunization, mean antibody titers to Y. pestis F1 and V antigens were measured and found to be significantly higher in vaccinates than their preimmunization values (P plague by subcutaneous inoculation. Eleven of 16 vaccinates (69 percent) survived with no ill effects whereas all eight control animals died within 3a??6 days. Two months later, the 11 surviving vaccinates were challenged again by ingestion of a plague-infected mouse. None of the animals showed any ill effects and all survived. In contrast, seven control ferrets fed infected mice died within 2a??4 days, including one animal that did not actually ingest the mouse but was likely exposed to it. This study demonstrates that immunization of ferrets with the recombinant F1-V fusion protein can induce significant antibody responses and reduce their susceptibility to plague infection.

  18. Pathogenesis and transmission of swine-origin 2009 A(H1N1) influenza virus in ferrets

    NARCIS (Netherlands)

    V.J. Munster (Vincent); E. de Wit (Emmie); J.M.A. van den Brand (Judith); S. Herfst (Sander); E.J.A. Schrauwen (Eefje); T.M. Bestebroer (Theo); D.A.M.C. van de Vijver (David); C.A.B. Boucher (Charles); M.P.G. Koopmans D.V.M. (Marion); G.F. Rimmelzwaan (Guus); T. Kuiken (Thijs); A.D.M.E. Osterhaus (Albert); R.A.M. Fouchier (Ron)

    2009-01-01

    textabstractThe swine-origin A(H1N1) influenza virus that has emerged in humans in early 2009 has raised concerns about pandemic developments. In a ferret pathogenesis and transmission model, the 2009 A(H1N1) influenza virus was found to be more pathogenic than a seasonal A(H1N1) virus, with more

  19. Implementing the use of a biobank in the endangered black-footed ferret (Mustela nigripes).

    Science.gov (United States)

    Santymire, Rachel

    2016-03-09

    In the current global health climate, many conservation biologists are managing crisis situations, including increased species extinction rates. One strategy for securing wildlife populations into the future is to preserve biomaterials in genome resource banks (GRB; or 'biobanks'). However, for GRBs to be successful we must understand the fundamental reproductive biology of species, along with developing assisted reproductive techniques (ARTs), including AI and semen cryopreservation. ART has been successfully used for several taxa, from amphibians to mammals, including ungulates, carnivores and primates. Not all these success stories implemented the use of a biobank, but one example that discussed herein is the black-footed ferret (Mustela nigripes) GRB. From a founder population of seven individuals, this species has been breeding in a managed setting for nearly 30 years. The goal of the breeding program is to maintain genetic integrity by ensuring each individual has the opportunity to pass his/her genes onto the next generation, while simultaneously providing animals for release into the wild. Scientists have used ART (e.g. AI) in the recovery program. Recently, semen from an individual of the founder population that was cryopreserved for up to 20 years was used successfully for AI, which improved the genetic diversity of the population. The black-footed ferret recovery program can serve as a model for other endangered species and demonstrates the usefulness of ART and GRBs to maintain highly endangered species into the future.

  20. Transmission of H7N9 Influenza Viruses with a Polymorphism at PB2 Residue 627 in Chickens and Ferrets

    Science.gov (United States)

    Luk, Geraldine S. M.; Leung, Connie Y. H.; Sia, Sin Fun; Choy, Ka-Tim; Zhou, Jie; Ho, Candy C. K.; Cheung, Peter P. H.; Lee, Elaine F.; Wai, Chris K. L.; Li, Pamela C. H.; Ip, Sin-Ming; Poon, Leo L. M.; Lindsley, William G.

    2015-01-01

    ABSTRACT Poultry exposure is a major risk factor for human H7N9 zoonotic infections, for which the mode of transmission remains unclear. We studied the transmission of genetically related poultry and human H7N9 influenza viruses differing by four amino acids, including the host determinant PB2 residue 627. A/Silkie chicken/HK/1772/2014 (SCk1772) and A/HK/3263/14 (HK3263) replicated to comparable titers in chickens, with superior oropharyngeal over cloacal shedding; both viruses transmitted efficiently among chickens via direct contact but inefficiently via the airborne route. Interspecies transmission via the airborne route was observed for ferrets exposed to the SCk1772- or HK3263-infected chickens, while low numbers of copies of influenza viral genome were detected in the air, predominantly at particle sizes larger than 4 μm. In ferrets, the human isolate HK3263 replicated to higher titers and transmitted more efficiently via direct contact than SCk1772. We monitored “intrahost” and “interhost” adaptive changes at PB2 residue 627 during infection and transmission of the Sck1772 that carried E627 and HK3263 that carried V/K/E polymorphism at 60%, 20%, and 20%, respectively. For SCk1772, positive selection for K627 over E627 was observed in ferrets during the chicken-to-ferret or ferret-to-ferret transmission. For HK3263 that contained V/K/E polymorphism, mixed V627 and E627 genotypes were transmitted among chickens while either V627 or K627 was transmitted to ferrets with a narrow transmission bottleneck. Overall, our results suggest direct contact as the main mode for H7N9 transmission and identify the PB2-V627 genotype with uncompromised fitness and transmissibility in both avian and mammalian species. IMPORTANCE We studied the modes of H7N9 transmission, as this information is crucial for developing effective control measures for prevention. Using chicken (SCk1772) and human (HK3263) H7N9 isolates that differed by four amino acids, including the host

  1. Intravenous immunoglobulins prevent the breakdown of the blood-brain barrier in experimentally induced sepsis.

    Science.gov (United States)

    Esen, Figen; Senturk, Evren; Ozcan, Perihan E; Ahishali, Bulent; Arican, Nadir; Orhan, Nurcan; Ekizoglu, Oguzhan; Kucuk, Mutlu; Kaya, Mehmet

    2012-04-01

    The effects of immunoglobulin G and immunoglobulins enriched with immunoglobulin A and immunoglobulin M on blood-brain barrier integrity and survival rates in septic rats were comparatively investigated. Sepsis was induced by cecal ligation and perforation in Sprague-Dawley rats. The animals were divided into the following groups: Sham, cecal ligation and perforation, cecal ligation and perforation plus immunoglobulin G (250 mg/kg, intravenous), and cecal ligation and perforation plus immunoglobulins enriched with immunoglobulin A and immunoglobulin M (250 mg/kg, intravenous). Immunoglobulins were administered 5 mins before cecal ligation and perforation and the animals were observed for behavioral changes for 24 hrs following cecal ligation and perforation. Blood-brain barrier permeability was functionally and structurally evaluated by determining the extravasation of Evans Blue and horseradish peroxidase tracers, respectively. Immunohistochemistry and Western blotting for occludin were performed. The high mortality rate (34%) noted in the septic rats was decreased to 15% and 3% by immunoglobulin G and immunoglobulins enriched with immunoglobulin A and immunoglobulin M, respectively (p immunoglobulin G and immunoglobulins enriched with immunoglobulin A and immunoglobulin M alleviated the symptoms of sickness behavior in the septic rats, with the animals becoming healthy and active. Increased extravasation of Evans Blue into the brain tissue of the septic rats was markedly decreased with the administration of both immunoglobulin G and immunoglobulins enriched with immunoglobulin A and immunoglobulin M (p immunoglobulin G or immunoglobulins enriched with immunoglobulin A and immunoglobulin M treatment, no ultrastructural evidence of leaky capillaries in the brain was observed in the septic rats, indicating the blockade of the transcellular pathway by immunoglobulins administration. Our study suggests that immunoglobulin G and immunoglobulins enriched with

  2. Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highly pathogenic influenza intranasal and intratracheal challenge.

    Directory of Open Access Journals (Sweden)

    Alex J Mann

    Full Text Available We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments or intranasally (CSN adjuvanted and placebo treatments only with clade 1 HPAI A/Vietnam/1194/2004 (H5N1 virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings. In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratracheal challenge; serologically, protective titres were demonstrable after one vaccination. The 2-dose schedule with TM-CSN vaccine also induced cross-reactive antibodies to clade 2.1 and 2.2 H5N1 viruses. Furthermore ferrets immunised with TM-CSN had no detectable virus in the respiratory tract or brain, whereas there were signs of virus in the throat and lungs, albeit at significantly reduced levels, in CSN vaccinated animals. This study demonstrated for the first time that CSN and in particular TM-CSN adjuvanted intranasal vaccines have the potential to protect against significant

  3. Low dose influenza virus challenge in the ferret leads to increased virus shedding and greater sensitivity to oseltamivir.

    Science.gov (United States)

    Marriott, Anthony C; Dove, Brian K; Whittaker, Catherine J; Bruce, Christine; Ryan, Kathryn A; Bean, Thomas J; Rayner, Emma; Pearson, Geoff; Taylor, Irene; Dowall, Stuart; Plank, Jenna; Newman, Edmund; Barclay, Wendy S; Dimmock, Nigel J; Easton, Andrew J; Hallis, Bassam; Silman, Nigel J; Carroll, Miles W

    2014-01-01

    Ferrets are widely used to study human influenza virus infection. Their airway physiology and cell receptor distribution makes them ideal for the analysis of pathogenesis and virus transmission, and for testing the efficacy of anti-influenza interventions and vaccines. The 2009 pandemic influenza virus (H1N1pdm09) induces mild to moderate respiratory disease in infected ferrets, following inoculation with 106 plaque-forming units (pfu) of virus. We have demonstrated that reducing the challenge dose to 102 pfu delays the onset of clinical signs by 1 day, and results in a modest reduction in clinical signs, and a less rapid nasal cavity innate immune response. There was also a delay in virus production in the upper respiratory tract, this was up to 9-fold greater and virus shedding was prolonged. Progression of infection to the lower respiratory tract was not noticeably delayed by the reduction in virus challenge. A dose of 104 pfu gave an infection that was intermediate between those of the 106 pfu and 102 pfu doses. To address the hypothesis that using a more authentic low challenge dose would facilitate a more sensitive model for antiviral efficacy, we used the well-known neuraminidase inhibitor, oseltamivir. Oseltamivir-treated and untreated ferrets were challenged with high (106 pfu) and low (102 pfu) doses of influenza H1N1pdm09 virus. The low dose treated ferrets showed significant delays in innate immune response and virus shedding, delayed onset of pathological changes in the nasal cavity, and reduced pathological changes and viral RNA load in the lung, relative to untreated ferrets. Importantly, these observations were not seen in treated animals when the high dose challenge was used. In summary, low dose challenge gives a disease that more closely parallels the disease parameters of human influenza infection, and provides an improved pre-clinical model for the assessment of influenza therapeutics, and potentially, influenza vaccines.

  4. A recombinant Hendra virus G glycoprotein-based subunit vaccine protects ferrets from lethal Hendra virus challenge.

    Science.gov (United States)

    Pallister, Jackie; Middleton, Deborah; Wang, Lin-Fa; Klein, Reuben; Haining, Jessica; Robinson, Rachel; Yamada, Manabu; White, John; Payne, Jean; Feng, Yan-Ru; Chan, Yee-Peng; Broder, Christopher C

    2011-08-05

    The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are two deadly zoonotic viruses for which no vaccines or therapeutics have yet been approved for human or livestock use. In 14 outbreaks since 1994 HeV has been responsible for multiple fatalities in horses and humans, with all known human infections resulting from close contact with infected horses. A vaccine that prevents virus shedding in infected horses could interrupt the chain of transmission to humans and therefore prevent HeV disease in both. Here we characterise HeV infection in a ferret model and show that it closely mirrors the disease seen in humans and horses with induction of systemic vasculitis, including involvement of the pulmonary and central nervous systems. This model of HeV infection in the ferret was used to assess the immunogenicity and protective efficacy of a subunit vaccine based on a recombinant soluble version of the HeV attachment glycoprotein G (HeVsG), adjuvanted with CpG. We report that ferrets vaccinated with a 100 μg, 20 μg or 4 μg dose of HeVsG remained free of clinical signs of HeV infection following a challenge with 5000 TCID₅₀ of HeV. In addition, and of considerable importance, no evidence of virus or viral genome was detected in any tissues or body fluids in any ferret in the 100 and 20 μg groups, while genome was detected in the nasal washes only of one animal in the 4 μg group. Together, our findings indicate that 100 μg or 20 μg doses of HeVsG vaccine can completely prevent a productive HeV infection in the ferret, suggesting that vaccination to prevent the infection and shedding of HeV is possible. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Sequential Seasonal H1N1 Influenza Virus Infections Protect Ferrets against Novel 2009 H1N1 Influenza Virus

    Science.gov (United States)

    Carter, Donald M.; Bloom, Chalise E.; Nascimento, Eduardo J. M.; Marques, Ernesto T. A.; Craigo, Jodi K.; Cherry, Joshua L.; Lipman, David J.

    2013-01-01

    Individuals H1N1 influenza. Many people >60 years old also had preexisting antibodies to novel H1N1. These observations are puzzling because the seasonal H1N1 viruses circulating during the last 60 years were not antigenically similar to novel H1N1. We therefore hypothesized that a sequence of exposures to antigenically different seasonal H1N1 viruses can elicit an antibody response that protects against novel 2009 H1N1. Ferrets were preinfected with seasonal H1N1 viruses and assessed for cross-reactive antibodies to novel H1N1. Serum from infected ferrets was assayed for cross-reactivity to both seasonal and novel 2009 H1N1 strains. These results were compared to those of ferrets that were sequentially infected with H1N1 viruses isolated prior to 1957 or more-recently isolated viruses. Following seroconversion, ferrets were challenged with novel H1N1 influenza virus and assessed for viral titers in the nasal wash, morbidity, and mortality. There was no hemagglutination inhibition (HAI) cross-reactivity in ferrets infected with any single seasonal H1N1 influenza viruses, with limited protection to challenge. However, sequential H1N1 influenza infections reduced the incidence of disease and elicited cross-reactive antibodies to novel H1N1 isolates. The amount and duration of virus shedding and the frequency of transmission following novel H1N1 challenge were reduced. Exposure to multiple seasonal H1N1 influenza viruses, and not to any single H1N1 influenza virus, elicits a breadth of antibodies that neutralize novel H1N1 even though the host was never exposed to the novel H1N1 influenza viruses. PMID:23115287

  6. Spatial and temporal use of a prairie dog colony by coyotes and rabbits: potential indirect effects on endangered black-footed ferrets

    Science.gov (United States)

    Eads, David A.; Biggins, Dean E.; Livieri, Travis M.

    2015-01-01

    In western North America, endangered black-footed ferrets Mustela nigripes are conserved via reintroduction to colonies of prairie dogs Cynomys spp., their primary prey. Predation is an important source of mortality; coyotes Canis latrans appear to be the most problematic predator, accounting for 67% of known predation events on radio-tagged ferrets. Little is known about what factors affect spatial use of prairie dog colonies by coyotes, or how other animals might affect interactions between coyotes and ferrets. During June–October 2007–2008, we used spotlight surveys to monitor coyotes and ferrets (both years) and rabbits Sylvilagus spp. (first year) on a 452-ha colony of black-tailed prairie dogs Cynomys ludovicianus in the Conata Basin, South Dakota. Coyotes appeared to select areas of the colony used by rabbits, suggesting coyotes hunted rabbits, a common item in their diet. Between midnight and sunrise, ferrets were most commonly observed during early morning (01:00–03:00 h), whereas coyotes were observed mostly during dawn (04:00 h – sunrise) when ferrets were rarely seen. These temporal differences in the timing of observations suggest ferrets tend to remain underground in burrows when coyotes are most active. Coyotes appeared to be attracted to rabbits in both space and time, suggesting the risk of predation for ferrets might relate to the abundance and locations of rabbits in prairie dog colonies.

  7. Subcutaneous Immunoglobulins: A Promising Alternative for Immunomodulation?

    Science.gov (United States)

    Sanchez-Ramon, Silvia; Corbi, Angel L; Fidalgo, Agueda Garcia; Dominguez-Soto, Angeles

    2016-01-01

    Cumulative recent evidence from clinical trials, observational studies and case reports has shown that subcutaneous administration of immunoglobulin (SCIg) exerts similar immunomodulatory capacity than intravenous immunoglobulin (IVIg) in autoimmune neurological diseases. Besides the beneficial clinical effects, the profile of safety and autonomy for the patient is higher for SCIg, while it is cost-saving in terms of the health resources used. However, there are still very few approved indications for SCIg and a certain resistance to choose SCIg for other autoimmune conditions even despite patients' interests. Here we present an updated review of the known immunomodulatory mechanisms of action of Ig and the current hypothesis supporting the clinical and immunological advantages of SCIg over IVIg that derive from their specific pharmacokinetic features. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. [Use of intravenous immunoglobulins in pediatrics].

    Science.gov (United States)

    Duse, M; Plebani, A; Crispino, P; Ugazio, A G

    1991-01-01

    Intramuscular Immunoglobulin (IMIG) have been used for 40 years in substitution therapy for antibody deficiencies and as prophylaxis for and treatment of several infectious diseases. Modified and intact intravenous immunoglobulin preparations (IVIG) have now been available for more than 10 years: only the intact product express full Fc- mediated functions with a biological half-life of IgG (3-4 weeks). These preparations have constituted an important achievement in the treatment of humoral immunodeficiencies also resulting in a dramatic improvement of the prognosis. The use of IVIG has also modified the therapeutic approach to several secondary and acquired immunodeficiencies. Treatment with IVIG for immune modulation in several diseases is investigated: substantial data indicate a useful role in selected cases of idiopathic thrombocytopenic purpura, Kawasaky disease and in some neurologic diseases. IVIG are substantially safe and severe side effects have been rarely reported.

  9. Intravenous immunoglobulin therapy for refractory recurrent pericarditis.

    Science.gov (United States)

    del Fresno, M Rosa; Peralta, Julio E; Granados, Miguel Ángel; Enríquez, Eugenia; Domínguez-Pinilla, Nerea; de Inocencio, Jaime

    2014-11-01

    Recurrent pericarditis is a troublesome complication of idiopathic acute pericarditis and occurs more frequently in pediatric patients after cardiac surgery (postpericardiotomy syndrome). Conventional treatment with nonsteroidal antiinflammatory drugs, corticosteroids, and colchicine is not always effective or may cause serious adverse effects. There is no consensus, however, on how to proceed in those patients whose disease is refractory to conventional therapy. In such cases, human intravenous immunoglobulin, immunosuppressive drugs, and biological agents have been used. In this report we describe 2 patients with refractory recurrent pericarditis after cardiac surgery who were successfully treated with 3 and 5 monthly high-dose (2 g/kg) intravenous immunoglobulin until resolution of the effusion. Our experience supports the effectiveness and safety of this therapy. Copyright © 2014 by the American Academy of Pediatrics.

  10. Rubella antibodies in Australian immunoglobulin products.

    Science.gov (United States)

    Young, Megan K; Bertolini, Joseph; Kotharu, Pushpa; Maher, Darryl; Cripps, Allan W

    2017-08-03

    Rubella antibodies are not routinely measured in immunoglobulin products and there is a lack of information on the titer in Australian products. To facilitate future studies of the effectiveness of passive immunisation for preventing rubella and congenital rubella syndrome, this study measured the concentration of rubella-specific antibodies in Australian intramuscular (IM) and intravenous (IV) human immunoglobulin products suitable for post-exposure prophylaxis using a chemiluminescent immunoassay. The GMT ± GSD for the IM product was 19 ± 1.2 IU/mg (2980 ± 1.2 IU/mL). The GMT ± GSD for the IV product was 12 ± 1.5 IU/mg (729 ± 1.5 IU/mL). At present, Australian guidelines recommend offering non-immune pregnant women exposed to rubella 20 mL of intramuscular immunoglobulin within 72 hours of exposure. This equates to 42,160 IU of rubella antibodies if the lowest titer obtained for the Australian IM product is considered. The same dose would be delivered by 176 mL of the Australian IV product at the lowest measured rubella-specific antibody titer.

  11. CAF01 potentiates immune responses and efficacy of an inactivated influenza vaccine in ferrets

    DEFF Research Database (Denmark)

    Martel, Cyril Jean-Marie; Agger, Else Marie; Poulsen, Julie Juul

    2011-01-01

    Trivalent inactivated vaccines (TIV) against influenza are given to 350 million people every year. Most of these are non-adjuvanted vaccines whose immunogenicity and protective efficacy are considered suboptimal. Commercially available non-adjuvanted TIV are known to elicit mainly a humoral immune...... response, whereas the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6'-dibehenate, CAF01) was developed. CAF01 has proven to enhance both humoral and cell-mediated immune responses to a number of different...... experimental vaccine candidates. In this study, we compared the immune responses in ferrets to a commercially available TIV with the responses to the same vaccine mixed with the CAF01 adjuvant. Two recently circulating H1N1 viruses were used as challenge to test the vaccine efficacy. CAF01 improved...

  12. Leucocytes, cytokines and satellite cells

    DEFF Research Database (Denmark)

    Paulsen, Gøran; Mikkelsen, Ulla Ramer; Raastad, Truls

    2012-01-01

    -damaging exercise', primarily eccentric exercise. We review the evidence for the notion that the degree of muscle damage is related to the magnitude of the cytokine response. In the third and final section, we look at the satellite cell response to a single bout of eccentric exercise, as well as the role...... variation in individual responses to a given exercise should, however be expected. The link between cytokine and satellite cell responses and exercise-induced muscle damage is not so clear The systemic cytokine response may be linked more closely to the metabolic demands of exercise rather than muscle...... damage. With the exception of IL-6, the sources of systemic cytokines following exercise remain unclear The satellite cell response to severe muscle damage is related to regeneration, whereas the biological significance of satellite cell proliferation after mild damage or non-damaging exercise remains...

  13. Transmission of aerosolized seasonal H1N1 influenza A to ferrets.

    Directory of Open Access Journals (Sweden)

    Heather MacInnes

    Full Text Available Influenza virus is a major cause of morbidity and mortality worldwide, yet little quantitative understanding of transmission is available to guide evidence-based public health practice. Recent studies of influenza non-contact transmission between ferrets and guinea pigs have provided insights into the relative transmission efficiencies of pandemic and seasonal strains, but the infecting dose and subsequent contagion has not been quantified for most strains. In order to measure the aerosol infectious dose for 50% (aID(50 of seronegative ferrets, seasonal influenza virus was nebulized into an exposure chamber with controlled airflow limiting inhalation to airborne particles less than 5 µm diameter. Airborne virus was collected by liquid impinger and Teflon filters during nebulization of varying doses of aerosolized virus. Since culturable virus was accurately captured on filters only up to 20 minutes, airborne viral RNA collected during 1-hour exposures was quantified by two assays, a high-throughput RT-PCR/mass spectrometry assay detecting 6 genome segments (Ibis T5000™ Biosensor system and a standard real time RT-qPCR assay. Using the more sensitive T5000 assay, the aID(50 for A/New Caledonia/20/99 (H1N1 was approximately 4 infectious virus particles under the exposure conditions used. Although seroconversion and sustained levels of viral RNA in upper airway secretions suggested established mucosal infection, viral cultures were almost always negative. Thus after inhalation, this seasonal H1N1 virus may replicate less efficiently than H3N2 virus after mucosal deposition and exhibit less contagion after aerosol exposure.

  14. Age-Dependent Sexually-Dimorphic Asymmetric Development of the Ferret Cerebellar Cortex

    Directory of Open Access Journals (Sweden)

    Kazuhiko Sawada

    2017-03-01

    Full Text Available A three-dimensional (3D T1-weighted Magnetic Resonance Imaging (MRI at 7-Tesla system was acquired with a high spatial resolution from fixed brains of male and female ferrets at postnatal days (PDs 4 to 90, and their age-related sexual difference and laterality were evaluated by MRI-based ex vivo volumetry. The volume of both left and right sides of cerebellar cortex was larger in males than in females on PD 10 and thereafter. When the cerebellar cortex was divided into four transverse domains, i.e., anterior zone (AZ; lobules I–V, central zone (CZ; lobules VI and VII, posterior zone (PZ; lobules VIII–IXa, and nodular zone (NZ; lobules IXb and X, an age-related significantly greater volume in males than in females was detected on either side of all four domains on PD 42 and of the AZ on PD 90, but only on the left side of the PZ on PD 90. Regarding the volume laterality, significant leftward asymmetry was obtained in the CZ and PZ volumes in males, but not in females on PD 90. From asymmetry quotient (AQ analysis, AQ scores were rightward in the AZ in both sexes already on PD 21, but gradually left-lateralized only in males in the CZ, PZ, and NZ during PDs 42 to 90. The present study suggests that a characteristic counterclockwise torque asymmetry (rostrally right-biased, and caudally left-biased or symmetrical is acquired in both sexes of ferrets during PDs 42 to 90, although the leftward laterality of the posterior half of the cerebellum was more enhanced in males.

  15. The Nuts and Bolts of Immunoglobulin Treatment for Antibody Deficiency.

    Science.gov (United States)

    Wasserman, Richard L

    Immunoglobulin therapy is a key element in the management of most patients with primary immunodeficiency disease. Allergist/immunologists should be familiar with the appropriate evaluation of candidates for immunoglobulin, the characteristics of immunoglobulin products, and how to use them to provide the best care to their patients. Available immunoglobulin products appear to be equally efficacious, but they are not interchangeable. Minimizing the risk of serious adverse events and controlling minor side effects is important to ideal patient care. Immunoglobulin may be administered intravenously or subcutaneously. Individualizing the choice of immunoglobulin product, mode of administration, and site of care can optimize the clinical outcome and minimize the burden of care. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. Successful treatment of systemic lupus erythematosus with subcutaneous immunoglobulin.

    Science.gov (United States)

    Brasileiro, A; Fonseca Oliveira, J; Pinheiro, S; Paiva-Lopes, M J

    2016-05-01

    The therapeutic efficacy of high-dose intravenous immunoglobulin in systemic lupus erythematosus (SLE) patients is well established. However, side effects might limit its use and lead to the consideration of therapeutic alternatives, such as the subcutaneous formulation of immunoglobulin, which has been used in some patients with other autoimmune diseases. We report a case of SLE refractory to classical therapies. High-dose intravenous immunoglobulin was effective, but gave rise to significant side effects. The patient was successfully treated with subcutaneous human immunoglobulin, achieving and maintaining clinical and laboratory remission. A lower immunoglobulin dose was needed and no side effects were observed, compared to the intravenous administration. Subcutaneous immunoglobulin could be a better-tolerated and cost-saving therapeutic option for select SLE patients. © The Author(s) 2016.

  17. The role of the interleukin-10 subfamily members in immunoglobulin production by human B cells

    DEFF Research Database (Denmark)

    Hummelshoj, L; Ryder, L P; Poulsen, Lars K.

    2006-01-01

    Interleukin (IL)-10 has been shown to have various effects on B cells, including positively affecting the production of immunoglobulin A (IgA) and IgG. Several human IL-10-related molecules have been identified. These include IL-19, IL-20, IL-22, IL-24, IL-26, IL-28 and IL-29. To determine...... the effects of the IL-10 analogues on the class switch recombination in B cells, we analysed Ig production from naïve B cells stimulated with these cytokines in the presence of anti-CD40. None of the cytokines were found to induce Ig production by themselves in the presence of anti-CD40 Ab. However, all...... cytokines inhibited the production of IgA and IgG induced by anti-CD40 Ab alone. In combination with anti-CD40 Ab and IL-4, IgG4 were inhibited in cultures stimulated with IL-20, IL-22, IL-26, IL-28 and IL-29 compared with IL-4 and anti-CD40 Ab alone, whereas all IL-10 analogues increased the production...

  18. Differences in the mechanical properties of the developing cerebral cortical proliferative zone between mice and ferrets at both the tissue and single-cell levels

    Directory of Open Access Journals (Sweden)

    Arata Nagasaka

    2016-11-01

    Full Text Available Cell-producing events in developing tissues are mechanically dynamic throughout the cell cycle. In many epithelial systems, cells are apicobasally tall, with nuclei and somata that adopt different apicobasal positions because nuclei and somata move in a cell cycle–dependent manner. This movement is apical during G2 phase and basal during G1 phase, whereas mitosis occurs at the apical surface. These movements are collectively referred to as interkinetic nuclear migration, and such epithelia are called pseudostratified. The embryonic mammalian cerebral cortical neuroepithelium is a good model for highly pseudostratified epithelia, and we previously found differences between mice and ferrets in both horizontal cellular density (greater in ferrets and nuclear/somal movements (slower during G2 and faster during G1 in ferrets. These differences suggest that neuroepithelial cells alter their nucleokinetic behavior in response to physical factors that they encounter, which may form the basis for evolutionary transitions towards more abundant brain-cell production from mice to ferrets and primates. To address how mouse and ferret neuroepithelia may differ physically in a quantitative manner, we used atomic force microscopy to determine that the vertical stiffness of their apical surface is greater in ferrets (Young’s modulus = 1700 Pa than in mice (1400 Pa. We systematically analyzed factors underlying the apical-surface stiffness through experiments to pharmacologically inhibit actomyosin or microtubules and to examine recoiling behaviors of the apical surface upon laser ablation and also through electron microscopy to observe adherens junction. We found that although both actomyosin and microtubules are partly responsible for the apical-surface stiffness, the mouse<ferret relationship in the apical-surface stiffness was maintained even in the presence of inhibitors. We also found that the stiffness of single, dissociated neuroepithelial cells is

  19. Serum immunoglobulins during and after postoperative radiotherapy of breast cancer

    International Nuclear Information System (INIS)

    Koehler, A.H.; Stoeck, R.

    1982-01-01

    In 115 operated patients with breast cancer of the TNM-B stages 1-3 the levels of immunoglobulins A, G and M were determined before and after radiotherapy. The results show that radiotherapy does not bring about significant change of the levels of immunoglobulins. Therefore the determination of the immunoglobulins is not suitable both for prognostic statements and as indicator of immunologic changes during radiotherapy. (author)

  20. New reassortant and enzootic European swine influenza 1 viruses transmits efficiently through direct contact in the ferret model

    DEFF Research Database (Denmark)

    Fobian, Kristina; P. Fabrizio, Thomas; Yoon, Sun-Woo

    2015-01-01

    The reverse zoonotic events that introduced the 2009 pandemic influenza virus into pigs have drastically increased the diversity of swine influenza viruses in Europe. The pandemic potential of these novel reassortments is still unclear, necessitating enhanced surveillance of European pigs...... and human-like N2 and one with 2009 pandemic H1 and swine-like N2. All viruses replicated to high titers in nasal wash- and nasal turbinate samples from inoculated ferrets and transmitted efficiently by direct contact. Only the H3N2 virus transmitted to naïve ferrets via the airborne route. Growth kinetics...... using a differentiated human bronchial epithelial cell line showed that all four viruses were able to replicate to high titers. Further, the viruses revealed preferential binding to the α2,6-silalylated glycans and investigation of the antiviral susceptibility of the viruses revealed that all were...

  1. Antigenically diverse swine-origin H1N1 variant influenza viruses exhibit differential ferret pathogenesis and transmission phenotypes.

    Science.gov (United States)

    Pulit-Penaloza, Joanna A; Jones, Joyce; Sun, Xiangjie; Jang, Yunho; Thor, Sharmi; Belser, Jessica A; Zanders, Natosha; Creager, Hannah M; Ridenour, Callie; Wang, Li; Stark, Thomas J; Garten, Rebecca; Chen, Li-Mei; Barnes, John; Tumpey, Terrence M; Wentworth, David E; Maines, Taronna R; Davis, C Todd

    2018-03-14

    Influenza A(H1) viruses circulating in swine represent an emerging virus threat as zoonotic infections occur sporadically following exposure to swine. A fatal infection caused by an H1N1 variant (H1N1v) virus was detected in a patient with reported exposure to swine and who presented with pneumonia, respiratory failure, and cardiac arrest. To understand the genetic and phenotypic characteristics of the virus, genome sequence analysis, antigenic characterization, and ferret pathogenesis and transmissibility experiments were performed. Antigenic analysis of the virus isolated from the fatal case, A/Ohio/09/2015, demonstrated significant antigenic drift away from classical swine H1N1 variant viruses and H1N1 pandemic 2009 viruses. A substitution in the H1 hemagglutinin (G155E) was identified that likely impacted antigenicity, and reverse genetics was employed to understand the molecular mechanism of antibody escape. Reversion of the substitution to 155G, in a reverse genetics A/Ohio/09/2015 virus, showed that this residue was central to the loss of hemagglutination inhibition by ferret antisera raised against a prototypical H1N1 pandemic 2009 virus (A/California/07/2009), as well as gamma lineage classical swine H1N1 viruses, demonstrating the importance of this residue for antibody recognition of this H1 lineage. When analyzed in the ferret model, A/Ohio/09/2015 and another H1N1v virus (A/Iowa/39/2015), as well as A/California/07/2009, replicated efficiently in the respiratory tract of ferrets. The two H1N1v viruses transmitted efficiently among cohoused ferrets, but respiratory droplet transmission studies showed that A/California/07/2009 transmitted through the air more efficiently. Pre-existing immunity to A/California/07/2009 did not fully protect ferrets from challenge with A/Ohio/09/2015. IMPORTANCE Human infections with classical swine influenza A(H1N1) viruses that circulate in pigs continue to occur in the United States following exposure to swine. To

  2. Serum Interleukin-4 and Total Immunoglobulin E in Nonatopic Alopecia Areata Patients and HLA-DRB1 Typing

    OpenAIRE

    Attia, Enas A. S.; El Shennawy, Dina; Sefin, Ashraf

    2010-01-01

    Background. Interleukin-4 (IL-4), a Th2 cytokine, can stimulate immunoglobulin E (IgE) transcription. No previous studies evaluated the genetic mechanisms in nonatopic AA patients with elevated serum IgE. Objective. To compare serum IL-4 and total IgE levels between Egyptian nonatopic AA patients and healthy subjects and to investigate a possible relation to HLA-DRB1 alleles. Results. Serum IL-4 and total IgE were measured by ELISA in 40 controls and 54 nonatopic AA patients. Patients' HL...

  3. Ectopic lymphoid tissues support local immunoglobulin production in patients with chronic rhinosinusitis with nasal polyps.

    Science.gov (United States)

    Song, Jia; Wang, Hai; Zhang, Ya-Na; Cao, Ping-Ping; Liao, Bo; Wang, Zhe-Zheng; Shi, Li-Li; Yao, Yin; Zhai, Guan-Ting; Wang, Zhi-Chao; Liu, Li-Meng; Zeng, Ming; Lu, Xiang; Wang, Heng; Yang, Xiang-Ping; Yu, Di; Bachert, Claus; Liu, Zheng

    2018-03-01

    The contribution of ectopic lymphoid tissues (eLTs) to local immunoglobulin hyperproduction in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is unclear. We sought to explore the cellular basis, formation mechanisms, and function of eLTs in patients with CRSwNP. We graded lymphoid aggregations in sinonasal mucosa and histologically studied their structures. The expression of lymphorganogenic factors and molecules required for immunoglobulin production was measured by using real-time PCR, and their localization was analyzed by means of immunohistochemistry and immunofluorescence. The phenotype of follicular helper T cells was analyzed by performing flow cytometry. Immunoglobulin levels were quantified by using the Bio-Plex assay or ImmunoCAP system. Nasal tissue explants were challenged ex vivo with Dermatophagoides pteronyssinus group 1 (Der p 1), and the expression of Iε-Cμ and Iε-Cγ circle transcripts was detected by using seminested PCR. Increased formation of eLTs with germinal center-like structures was discovered in patients with eosinophilic (20.69%) and noneosinophilic (17.31%) CRSwNP compared with that in patients with chronic rhinosinusitis without nasal polyps (5.66%) and control subjects (3.70%). The presence of eLTs was associated with increased expression of lymphorganogenic and inflammatory chemokines and cytokines, as well as their receptors. The expression of molecules required for immunoglobulin production, generation of follicular helper T cells, and production of IgE in eosinophilic polyps and IgG and IgA in both eosinophilic and noneosinophilic polyps were predominantly upregulated in patients with eLTs. After Der p 1 challenge ex vivo, Iε-Cμ transcript was detected only in eosinophilic polyps with eLTs but not in polyps without eLTs and noneosinophilic polyps. eLTs might support local immunoglobulin production and therefore significantly contribute to the development of CRSwNP. Copyright © 2017 American Academy of

  4. Cytokines in Sjogren's syndrome: potential therapeutic targets

    NARCIS (Netherlands)

    Roescher, N.; Tak, P.P.; Illei, G.G.

    2010-01-01

    The dysregulated cytokine network in Sjogren's Syndrome (SS) is reflected by local and systemic overexpression of pro-inflammatory cytokines and absent or low levels of anti-inflammatory cytokines. To date, the use of cytokine based therapies in SS has been disappointing. Oral administration of low

  5. Evidence for Radiation-Induced Disseminated Intravascular Coagulation as a Major Cause of Radiation-Induced Death in Ferrets

    Energy Technology Data Exchange (ETDEWEB)

    Krigsfeld, Gabriel S.; Savage, Alexandria R.; Billings, Paul C.; Lin, Liyong; Kennedy, Ann R., E-mail: akennedy@mail.med.upenn.edu

    2014-03-15

    Purpose: The studies reported here were performed as part of a program in space radiation biology in which proton radiation like that present in solar particle events, as well as conventional gamma radiation, were being evaluated in terms of the ability to affect hemostasis. Methods and Materials: Ferrets were exposed to 0 to 2 Gy of whole-body proton or gamma radiation and monitored for 30 days. Blood was analyzed for blood cell counts, platelet clumping, thromboelastometry, and fibrin clot formation. Results: The lethal dose of radiation to 50% of the population (LD{sub 50}) of the ferrets was established at ∼1.5 Gy, with 100% mortality at 2 Gy. Hypocoagulability was present as early as day 7 postirradiation, with animals unable to generate a stable clot and exhibiting signs of platelet aggregation, thrombocytopenia, and fibrin clots in blood vessels of organs. Platelet counts were at normal levels during the early time points postirradiation when coagulopathies were present and becoming progressively more severe; platelet counts were greatly reduced at the time of the white blood cell nadir of 13 days. Conclusions: Data presented here provide evidence that death at the LD{sub 50} in ferrets is most likely due to disseminated intravascular coagulation (DIC). These data question the current hypothesis that death at relatively low doses of radiation is due solely to the cell-killing effects of hematopoietic cells. The recognition that radiation-induced DIC is the most likely mechanism of death in ferrets raises the question of whether DIC is a contributing mechanism to radiation-induced death at relatively low doses in large mammals.

  6. Vicks VapoRub induces mucin secretion, decreases ciliary beat frequency, and increases tracheal mucus transport in the ferret trachea.

    Science.gov (United States)

    Abanses, Juan Carlos; Arima, Shinobu; Rubin, Bruce K

    2009-01-01

    Vicks VapoRub (VVR) [Proctor and Gamble; Cincinnati, OH] is often used to relieve symptoms of chest congestion. We cared for a toddler in whom severe respiratory distress developed after VVR was applied directly under her nose. We hypothesized that VVR induced inflammation and adversely affected mucociliary function, and tested this hypothesis in an animal model of airway inflammation. [1] Trachea specimens excised from 15 healthy ferrets were incubated in culture plates lined with 200 mg of VVR, and the mucin secretion was compared to those from controls without VVR. Tracheal mucociliary transport velocity (MCTV) was measured by timing the movement of 4 microL of mucus across the trachea. Ciliary beat frequency (CBF) was measured using video microscopy. [2] Anesthetized and intubated ferrets inhaled a placebo or VVR that was placed at the proximal end of the endotracheal tube. We evaluated both healthy ferrets and animals in which we first induced tracheal inflammation with bacterial endotoxin (a lipopolysaccharide [LPS]). Mucin secretion was measured using an enzyme-linked lectin assay, and lung water was measured by wet/dry weight ratios. [1] Mucin secretion was increased by 63% over the controls in the VVR in vitro group (p < 0.01). CBF was decreased by 35% (p < 0.05) in the VVR group. [2] Neither LPS nor VVR increased lung water, but LPS decreased MCTV in both normal airways (31%) and VVR-exposed airways (30%; p = 0.03), and VVR increased MCTV by 34% in LPS-inflamed airways (p = 0.002). VVR stimulates mucin secretion and MCTV in the LPS-inflamed ferret airway. This set of findings is similar to the acute inflammatory stimulation observed with exposure to irritants, and may lead to mucus obstruction of small airways and increased nasal resistance.

  7. 1918 pandemic H1N1 DNA vaccine protects ferrets against 2007 H1N1 virus infection

    DEFF Research Database (Denmark)

    Bragstad, Karoline; Martel, Cyril Jean-Marie; Aasted, Bent

    of the H1N1 pandemic virus from 1918 induce protection in ferrets against infection with a H1N1 (A/New Caledonia/20/99(H1N1)) virus which was included in the conventional vaccine for the 2006-2007 season. The viruses are separated by a time interval of 89 years and differ by 21.2% in the HA1 protein...

  8. Novel avian-origin human influenza A(H7N9) can be transmitted between ferrets via respiratory droplets.

    Science.gov (United States)

    Xu, Lili; Bao, Linlin; Deng, Wei; Dong, Libo; Zhu, Hua; Chen, Ting; Lv, Qi; Li, Fengdi; Yuan, Jing; Xiang, Zhiguang; Gao, Kai; Xu, Yanfeng; Huang, Lan; Li, Yanhong; Liu, Jiangning; Yao, Yanfeng; Yu, Pin; Li, Xiyan; Huang, Weijuan; Zhao, Xiang; Lan, Yu; Guo, Junfeng; Yong, Weidong; Wei, Qiang; Chen, Honglin; Zhang, Lianfeng; Qin, Chuan

    2014-02-15

    The outbreak of human infections caused by novel avian-origin influenza A(H7N9) in China since March 2013 underscores the need to better understand the pathogenicity and transmissibility of these viruses in mammals. In a ferret model, the pathogenicity of influenza A(H7N9) was found to be less than that of an influenza A(H5N1) strain but comparable to that of 2009 pandemic influenza A(H1N1), based on the clinical signs, mortality, virus dissemination, and results of histopathologic analyses. Influenza A(H7N9) could replicate in the upper and lower respiratory tract, the heart, the liver, and the olfactory bulb. It is worth noting that influenza A(H7N9) exhibited a low level of transmission between ferrets via respiratory droplets. There were 4 mutations in the virus isolated from the contact ferret: D678Y in the gene encoding PB2, R157K in the gene encoding hemagglutinin (H3 numbering), I109T in the gene encoding nucleoprotein, and T10I in the gene encoding neuraminidase. These data emphasized that avian-origin influenza A(H7N9) can be transmitted between mammals, highlighting its potential for human-to-human transmissibility.

  9. Environmental Conditions Affect Exhalation of H3N2 Seasonal and Variant Influenza Viruses and Respiratory Droplet Transmission in Ferrets.

    Directory of Open Access Journals (Sweden)

    Kortney M Gustin

    Full Text Available The seasonality of influenza virus infections in temperate climates and the role of environmental conditions like temperature and humidity in the transmission of influenza virus through the air are not well understood. Using ferrets housed at four different environmental conditions, we evaluated the respiratory droplet transmission of two influenza viruses (a seasonal H3N2 virus and an H3N2 variant virus, the etiologic virus of a swine to human summertime infection and concurrently characterized the aerosol shedding profiles of infected animals. Comparisons were made among the different temperature and humidity conditions and between the two viruses to determine if the H3N2 variant virus exhibited enhanced capabilities that may have contributed to the infections occurring in the summer. We report here that although increased levels of H3N2 variant virus were found in ferret nasal wash and exhaled aerosol samples compared to the seasonal H3N2 virus, enhanced respiratory droplet transmission was not observed under any of the environmental settings. However, overall environmental conditions were shown to modulate the frequency of influenza virus transmission through the air. Transmission occurred most frequently at 23°C/30%RH, while the levels of infectious virus in aerosols exhaled by infected ferrets agree with these results. Improving our understanding of how environmental conditions affect influenza virus infectivity and transmission may reveal ways to better protect the public against influenza virus infections.

  10. FEEDING OF FERRETS WITH THE RAW MEAT AND LIVER OF CHICKENS CHRONICALLY POISONED WITH TOXIC GROUNDNUT MEAL.

    Science.gov (United States)

    PLATONOW, N; BEAUREGARD, M

    1965-03-01

    Chickens were fed a ration containing 30 per cent of toxic groundnut meal for up to six weeks. The concentration of aflatoxin (toxic metabolites of Aspergillus flavus) in the above ration was 3.06 p.p.m. At the end of 2nd, 4th or 6th week the birds were killed. The meat was removed from the bones and put through a meat grinder. The livers of three groups were pooled together. Three control groups of birds kept on commercial pellets were treated similarly. Female ferrets, two years of age, were used in the present study. They were divided into four groups. The first three groups were given for one month meat from chickens fed the toxic ration for 2, 4, and 6 weeks, respectively. Each of these three groups contained one control ferret that was fed with the meat of chickens fed a commercial ration for a similar period of time. One half of the 4th group was fed pooled liver from intoxicated birds and one half was fed liver from control birds. No significant changes in the ferret tissues were observed as a consequence of feeding them with the meat or liver from the chickens chronically poisoned with toxic groundnut meal.

  11. Disruption of neuroendocrine stress responses to acute ferret odor by medial, but not central amygdala lesions in rats.

    Science.gov (United States)

    Masini, Cher V; Sasse, Sarah K; Garcia, Robert J; Nyhuis, Tara J; Day, Heidi E W; Campeau, Serge

    2009-09-08

    Investigations of the neural pathways associated with responses to predators have implicated the medial amygdala (MeA) as an important region involved in defensive behaviors. To our knowledge, however, the involvement of the MeA in neuroendocrine responses to predator odor exposure has not been investigated. Therefore, the present study examined the effects of MeA disruption in rats exposed to ferret or control odor on hypothalamo-pituitary-adrenocortical (HPA) axis activation. Bilateral lesions of the MeA were made in Sprague-Dawley rats with the neurotoxin ibotenic acid (10 microg/microl; 0.3 microl / side). As a control for regional specificity, additional groups of rats were given lesions in the central amygdala (CeA). One week after recovery, the rats were exposed to ferret or strawberry control towels in small cages to examine HPA axis responses as determined by plasma corticosterone and adrenocorticotropin hormone (ACTH) levels. Rats with complete bilateral MeA but not CeA lesions displayed significantly less corticosterone and ACTH release compared to sham-operated control rats only in the ferret odor conditions. These results suggest that the MeA is an important structure involved in the HPA axis responses to predator odors, in support of previous studies investigating behavioral responses under similar conditions.

  12. Use of a GnRH vaccine, GonaCon, for prevention and treatment of adrenocortical disease (ACD) in domestic ferrets.

    Science.gov (United States)

    Miller, Lowell A; Fagerstone, Kathleen A; Wagner, Robert A; Finkler, Mark

    2013-09-23

    Adrenocortical disease (ACD) is a common problem in surgically sterilized, middle-aged to old ferrets (Mustela putorius furo). The adrenal tissues of these ferrets develop hyperplasia, adenomas, or adenocarcinomas, which produce steroid hormones including estradiol, 17-hydroxyprogesterone, and androstenedione. Major clinical signs attributable to overproduction of these hormones are alopecia (hair loss) in both sexes and a swollen vulva in females. Pruritus, muscle atrophy, hind limb weakness, and sexual activity or aggression are also observed in both sexes. Males can develop prostatic cysts, prostatitis, and urethral obstruction. ACD is thought to be linked to continuous and increased LH secretion, due to lack of gonadal hormone feedback in neutered ferrets. This continuous elevated LH acts on adrenal cortex LH receptors, resulting in adrenal hyperplasia or adrenal tumor. This study investigated whether the immunocontraceptive vaccine GonaCon, a GnRH vaccine developed to reduce the fertility of wildlife species and the spread of disease, could prevent or delay onset of ACD and treat alopecia in ferrets with existing ACD. Results showed that GonaCon provided relief from ACD by causing production of antibodies to GnRH, probably suppressing production and/or release of LH. Treatment caused many ACD symptoms to disappear, allowing the ferrets to return to a normal life. The study also found that the probability of developing ACD was significantly reduced in ferrets treated with GonaCon when young (1-3 years old) compared to untreated control animals. GonaCon caused injection site reaction in some animals when administered as an intramuscular injection but caused few side effects when administered subcutaneously. Both intramuscular and subcutaneous vaccination resulted in similar levels of GnRH antibody titers. Subcutaneous vaccination with GonaCon is thus recommended to prevent the onset of ACD and as a possible treatment for ACD-signs in domestic ferrets. Published

  13. Screening for congenital toxoplasmosis: accuracy of immunoglobulin M and immunoglobulin A tests after birth

    DEFF Research Database (Denmark)

    Gilbert, Ruth E; Thalib, Lukman; Tan, Hooi Kuan

    2007-01-01

    OBJECTIVES: To determine the accuracy of postnatal screening for toxoplasma-specific immunoglobulin (Ig) M and IgA. SETTING: Ten centres in three European countries. METHODS: We compared results of the first postnatal IgM or IgA test in infants with infected mothers identified by prenatal screeni...

  14. Use of cytokines in infection.

    Science.gov (United States)

    Aoki, Naoko; Xing, Zhou

    2004-11-01

    Infectious disease remains an ever-growing health concern worldwide due to increasing antibiotic-resistant microbial strains, immune-compromised populations, international traffic and globalisation, and bioterrorism. There exists an urgent need to develop novel prophylactic and therapeutic strategies. In addition to classic antibiotic therapeutics, immune-modulatory molecules such as cytokines or their inhibitors represent a promising form of antimicrobial therapeutics or immune adjuvant used for the purpose of vaccination. These molecules, in the form of either recombinant protein or transgene, exert their antimicrobial effect by enhancing infectious agent-specific immune activation or memory development, or by dampening undesired inflammatory and immune responses resulting from infection and host defence mechanisms. In the last two decades, a number of cytokine therapy-based experimental and clinical trials have been conducted, and some of these efforts have led to the routine clinical use of cytokines. For instance, although IFNs have been used to treat hepatitis C with great success, many other cytokines are yet to be fully evaluated for their antimicrobial potential. This review discusses the biology and therapeutic potential of selected immune modulatory cytokines and their inhibitors, including granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, IFN-gamma, IL-12 and TNF.

  15. Cytokine network in psoriasis revisited.

    Science.gov (United States)

    Michalak-Stoma, Anna; Pietrzak, Aldona; Szepietowski, Jacek C; Zalewska-Janowska, Anna; Paszkowski, Tomasz; Chodorowska, Grażyna

    2011-12-01

    Psoriasis is a chronic genetically determined, erythemato-squamous disease associated with many comorbidities. Evidence from clinical studies and experimental models support the concept that psoriasis is a T cell-mediated inflammatory skin disease and T helper (Th) cells - Th1, Th17 and Th22 - play an important role in the pathogenesis. Th1 cytokines IFNγ, IL-2, as well as Th17 cytokines IL-17A, IL-17F, IL-22, IL-26, and TNFα (Th1 and Th17 cytokine) are increased in serum and lesional skin. IL-22 produced by Th17 and new subset of T helper cells, Th22, is also increased within psoriatic lesions and in the serum. Other recently recognized cytokines of significant importance in psoriasis are IL-23, IL-20 and IL-15. The IL-23/Th17 pathway plays a dominant role in psoriasis pathogenesis. Currently due to enormous methodological progress, more and more clinical and histopathological psoriatic features could be explained by particular cytokine imbalance, which still is one of the most fascinating dermatological research fields stimulating new and new generations of researchers.

  16. Immunoglobulin Fc gamma receptor promotes immunoglobulin uptake, immunoglobulin-mediated calcium increase, and neurotransmitter release in motor neurons

    Science.gov (United States)

    Mohamed, Habib A.; Mosier, Dennis R.; Zou, Ling L.; Siklos, Laszlo; Alexianu, Maria E.; Engelhardt, Jozsef I.; Beers, David R.; Le, Wei-dong; Appel, Stanley H.

    2002-01-01

    Receptors for the Fc portion of immunoglobulin G (IgG; FcgammaRs) facilitate IgG uptake by effector cells as well as cellular responses initiated by IgG binding. In earlier studies, we demonstrated that amyotrophic lateral sclerosis (ALS) patient IgG can be taken up by motor neuron terminals and transported retrogradely to the cell body and can alter the function of neuromuscular synapses, such as increasing intracellular calcium and spontaneous transmitter release from motor axon terminals after passive transfer. In the present study, we examined whether FcgammaR-mediated processes can contribute to these effects of ALS patient immunoglobulins. F(ab')(2) fragments (which lack the Fc portion) of ALS patient IgG were not taken up by motor axon terminals and were not retrogradely transported. Furthermore, in a genetically modified mouse lacking the gamma subunit of the FcR, the uptake of whole ALS IgG and its ability to enhance intracellular calcium and acetylcholine release were markedly attenuated. These data suggest that FcgammaRs appear to participate in IgG uptake into motor neurons as well as IgG-mediated increases in intracellular calcium and acetylcholine release from motor axon terminals. Copyright 2002 Wiley-Liss, Inc.

  17. Cytokine Immunopathogenesis of Enterovirus 71 Brain Stem Encephalitis

    Directory of Open Access Journals (Sweden)

    Shih-Min Wang

    2012-01-01

    Full Text Available Enterovirus 71 (EV71 is one of the most important causes of herpangina and hand, foot, and mouth disease. It can also cause severe complications of the central nervous system (CNS. Brain stem encephalitis with pulmonary edema is the severe complication that can lead to death. EV71 replicates in leukocytes, endothelial cells, and dendritic cells resulting in the production of immune and inflammatory mediators that shape innate and acquired immune responses and the complications of disease. Cytokines, as a part of innate immunity, favor the development of antiviral and Th1 immune responses. Cytokines and chemokines play an important role in the pathogenesis EV71 brain stem encephalitis. Both the CNS and the systemic inflammatory responses to infection play important, but distinctly different, roles in the pathogenesis of EV71 pulmonary edema. Administration of intravenous immunoglobulin and milrinone, a phosphodiesterase inhibitor, has been shown to modulate inflammation, to reduce sympathetic overactivity, and to improve survival in patients with EV71 autonomic nervous system dysregulation and pulmonary edema.

  18. [Dermatomyositis and Panniculitis: the function of immunoglobulins].

    Science.gov (United States)

    Abdelhafidh, Nadia Ben; Toujeni, Sana; Kefi, Asma; Bousetta, Najeh; Sayhi, Sameh; Gharsallah, Imen; Othmani, Salah

    2016-01-01

    Panniculitis is an inflammatory disease of subcutaneous adipose tissue which is rarely associated with dermatomyositis. It can occur before, after or simultaneously with muscle damage. In most cases, the evolution of panniculitis and of other dermatomyositis affections is favorable with corticosteroids and/or immunosuppressants. We report the case of a 48 year-old patient who developed panniculitis lesions 2 months before having muscular signs. Skin involvement was resistant to corticosteroid treatment associated with immunosuppressants drugs. This led to the use of polyvalent immunoglobulin treatment improving both skin and muscle damage.

  19. Immunoglobulin therapy for enteroviral meningitides in children

    Directory of Open Access Journals (Sweden)

    O. G. Kimirilova

    2016-01-01

    Full Text Available The authors give the material of their own observations on the clinical and laboratory efficacy of the Russian intravenous immunoglobulin Gabriglobin for the treatment of enteroviral meningitides in children.The performed trials indicated that the use of Gabriglobin in the combination therapy of severe enteroviral meningitides in children reduced the duration of intoxication, global cerebral symptoms, meningeal syndrome, the time of cerebrospinal fluid sanitation by 1,5 times, and that of in-hospital treatment by 5,8±1,8 days as compared to those who received conventional basic therapy.

  20. Immunoglobulin Replacement Therapy: When You Need It -- and When You Don't

    Science.gov (United States)

    ... Search Patient Resources Adult Immunoglobulin Replacement Therapy Immunoglobulin Replacement Therapy When you need it—and when you ... germ-fighting antibodies. A treatment known as immunoglobulin replacement (IgG) therapy can be a lifesaver for them. ...

  1. Neural Cell Adhesion Molecules of the Immunoglobulin Superfamily Regulate Synapse Formation, Maintenance, and Function.

    Science.gov (United States)

    Sytnyk, Vladimir; Leshchyns'ka, Iryna; Schachner, Melitta

    2017-05-01

    Immunoglobulin superfamily adhesion molecules are among the most abundant proteins in vertebrate and invertebrate nervous systems. Prominent family members are the neural cell adhesion molecules NCAM and L1, which were the first to be shown to be essential not only in development but also in synaptic function and as key regulators of synapse formation, synaptic activity, plasticity, and synaptic vesicle recycling at distinct developmental and activity stages. In addition to interacting with each other, adhesion molecules interact with ion channels and cytokine and neurotransmitter receptors. Mutations in their genes are linked to neurological disorders associated with abnormal development and synaptic functioning. This review presents an overview of recent studies on these molecules and their crucial impact on neurological disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Malaria: toxins, cytokines and disease

    DEFF Research Database (Denmark)

    Jakobsen, P H; Bate, C A; Taverne, J

    1995-01-01

    In this review the old concept of severe malaria as a toxic disease is re-examined in the light of recent discoveries in the field of cytokines. Animal studies suggest that the induction of TNF by parasite-derived molecules may be partly responsible for cerebral malaria and anemia, while hypoglyc......In this review the old concept of severe malaria as a toxic disease is re-examined in the light of recent discoveries in the field of cytokines. Animal studies suggest that the induction of TNF by parasite-derived molecules may be partly responsible for cerebral malaria and anemia, while...

  3. The immunoglobulins of cold-blooded vertebrates.

    Science.gov (United States)

    Pettinello, Rita; Dooley, Helen

    2014-11-24

    Although lymphocyte-like cells secreting somatically-recombining receptors have been identified in the jawless fishes (hagfish and lamprey), the cartilaginous fishes (sharks, skates, rays and chimaera) are the most phylogenetically distant group relative to mammals in which bona fide immunoglobulins (Igs) have been found. Studies of the antibodies and humoral immune responses of cartilaginous fishes and other cold-blooded vertebrates (bony fishes, amphibians and reptiles) are not only revealing information about the emergence and roles of the different Ig heavy and light chain isotypes, but also the evolution of specialised adaptive features such as isotype switching, somatic hypermutation and affinity maturation. It is becoming increasingly apparent that while the adaptive immune response in these vertebrate lineages arose a long time ago, it is most definitely not primitive and has evolved to become complex and sophisticated. This review will summarise what is currently known about the immunoglobulins of cold-blooded vertebrates and highlight the differences, and commonalities, between these and more "conventional" mammalian species.

  4. Autoantibodies and immunoglobulins among atomic bomb survivors

    International Nuclear Information System (INIS)

    Fujiwara, Saeko; Akahoshi, Masazumi; Kodama, Kazunori; Shimaoka, Katsutaro; Akiyama, Mitoshi; Carter, R.L.; Yamakido, Michio

    1994-01-01

    The purpose of this study was to determine if exposure to atomic bomb radiation affects immune responsiveness, such as the occurrence of autoantibodies and levels of immunoglobulins. Rheumatoid factor, antinuclear antibody, antithyroglobulin antibody, anti-thyroid-microsomal antibody and immunoglobulin levels (IgG, IgM, IgA and IgE) were measured among 2,061 individuals exposed to atomic bomb radiation in Hiroshima and Nagasaki whose estimated doses ranged from 0 to 5.6 Gy. The prevalence and titers of rheumatoid factor were found to be increased in the individuals exposed to higher radiation doses. The IgA level in females and the IgM level in both sexes increased as radiation dose increased, although the effects of radiation exposure were not large. No effect of radiation was found on the prevalence of antinuclear antibody, antithyroglobulin antibody and anti-thyroid-microsomal antibody or on the levels of IgG and IgE. 32 refs., 2 figs., 3 tabs

  5. Identification of sequence variants influencing immunoglobulin levels.

    Science.gov (United States)

    Jonsson, Stefan; Sveinbjornsson, Gardar; de Lapuente Portilla, Aitzkoa Lopez; Swaminathan, Bhairavi; Plomp, Rosina; Dekkers, Gillian; Ajore, Ram; Ali, Mina; Bentlage, Arthur E H; Elmér, Evelina; Eyjolfsson, Gudmundur I; Gudjonsson, Sigurjon A; Gullberg, Urban; Gylfason, Arnaldur; Halldorsson, Bjarni V; Hansson, Markus; Holm, Hilma; Johansson, Åsa; Johnsson, Ellinor; Jonasdottir, Aslaug; Ludviksson, Bjorn R; Oddsson, Asmundur; Olafsson, Isleifur; Olafsson, Sigurgeir; Sigurdardottir, Olof; Sigurdsson, Asgeir; Stefansdottir, Lilja; Masson, Gisli; Sulem, Patrick; Wuhrer, Manfred; Wihlborg, Anna-Karin; Thorleifsson, Gudmar; Gudbjartsson, Daniel F; Thorsteinsdottir, Unnur; Vidarsson, Gestur; Jonsdottir, Ingileif; Nilsson, Björn; Stefansson, Kari

    2017-08-01

    Immunoglobulins are the effector molecules of the adaptive humoral immune system. In a genome-wide association study of 19,219 individuals, we found 38 new variants and replicated 5 known variants associating with IgA, IgG or IgM levels or with composite immunoglobulin traits, accounted for by 32 loci. Variants at these loci also affect the risk of autoimmune diseases and blood malignancies and influence blood cell development. Notable associations include a rare variant at RUNX3 decreasing IgA levels by shifting isoform proportions (rs188468174[C>T]: P = 8.3 × 10 -55 , β = -0.90 s.d.), a rare in-frame deletion in FCGR2B abolishing IgG binding to the encoded receptor (p.Asn106del: P = 4.2 × 10 -8 , β = 1.03 s.d.), four IGH locus variants influencing class switching, and ten new associations with the HLA region. Our results provide new insight into the regulation of humoral immunity.

  6. Intravenous polyclonal human immunoglobulins in multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, Per Soelberg

    2008-01-01

    Intravenous immunoglobulin (IVIG) is an established therapy for demyelinating diseases of the peripheral nervous system. IVIG exerts a number of effects that may be beneficial in multiple sclerosis (MS). Four double-blind IVIG trials have been performed in relapsing-remitting MS. A meta-analysis ......Intravenous immunoglobulin (IVIG) is an established therapy for demyelinating diseases of the peripheral nervous system. IVIG exerts a number of effects that may be beneficial in multiple sclerosis (MS). Four double-blind IVIG trials have been performed in relapsing-remitting MS. A meta......-analysis of the four trials has shown that IVIG reduces the relapse rate and, possibly, disease progression. In patients with a first episode of demyelinating disease, IVIG delays the time to the second relapse and thereby to the diagnosis of definite MS. In patients with an acute MS relapse, IVIG as add-on therapy...... to methylprednisolone does not make remission of symptoms faster or more complete. IVIG does not seem to be of any benefit to chronic visual or motor symptoms in MS. In secondary progressive MS, IVIG has not shown any effect on disease progression, relapses or new magnetic resonance imaging lesions. Experimental...

  7. Pasteurization of IgM-enriched Immunoglobulin

    Directory of Open Access Journals (Sweden)

    Kamran Mousavi Hosseini

    2004-06-01

    Full Text Available Human plasma proteins are important for therapy or prophylaxis of human diseases. Due to the preparation of human plasma proteins from human plasma pools and risk of contamination with human viruses, different viral reduction treatments such as: pasteurization, solvent/detergent, dry heat treatment, steam treatment, beta-propiolactone/UV and nanofiltration have been implemented. As pasteurization can be performed for liquid protein, this method (a 10-hour heat treatment of the aqueous solutions at 60°C was introduced into the manufacturing procedure of IgM-enriched immunoglobulin, to improve its safety further. The efficiency of this method for inactivation of viruses was evaluated by the use of Foot-and-Mouth Disease Virus (a non-enveloped virus and Infectious Bovine Rhinotracheitis (IBR Virus (a lipid-enveloped virus. Pasteurization inactivated Foot-and-Mouth Disease Virus by 7 log10 and for IBR Virus by 5log10. These findings show a significant added measure of virus safety associated with pasteurization of IgM-enriched immunoglobulin preparation.

  8. Intravenous immunoglobulin therapy and systemic lupus erythematosus.

    Science.gov (United States)

    Zandman-Goddard, Gisele; Levy, Yair; Shoenfeld, Yehuda

    2005-12-01

    Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with diverse manifestations. We suggest that intravenous immunoglobulin (IVIg) therapy may be beneficial and safe for various manifestations in SLE. A structured literature search of articles published on the efficacy of IVIg in the treatment of SLE between 1983 and 2005 was conducted. We searched the terms "IVIg," "intravenous immunoglobulin," "lupus," "SLE," and "systemic lupus erythematosus." The various clinical manifestations of SLE that were reported to be successfully treated by IVIg in case reports include autoimmune hemolytic anemia, acquired factor VIII inhibitors, acquired von Willebrand disease, pure red cell aplasia, thrombocytopenia, pancytopenia, myelofibrosis, pneumonitis, pleural effusion, pericarditis, myocarditis, cardiogenic shock, nephritis, end-stage renal disease, encephalitis, neuropsychiatric lupus, psychosis, peripheral neuropathy, polyradiculoneuropathy, and vasculitis. The most extensive experience is with lupus nephritis. There are only a few case series of IVIg use in patients with SLE with various manifestations, in which the response rate to IVIg therapy ranged from 33 to 100%. We suggest that IVIg devoid of sucrose, at a dose of 2 g/kg over a 5-d period given uniformly and at a slow infusion rate in patients without an increased risk for thromboembolic events or renal failure, is a safe and beneficial adjunct therapy for cases of SLE that are resistant to or refuse conventional treatment. The duration of therapy is yet to be established. Controlled trials are warranted.

  9. Ingestion of host immunoglobulin by Sarcoptes scabiei

    Directory of Open Access Journals (Sweden)

    Simson Tarigan

    2005-03-01

    Full Text Available Scabies is one of the most important diseases in human and veterinary medicine. The available control measures that rely on acaricides are unsustainable, costly and environmentally unfriendly. Vaccination which is supposedly the most attractive alternative control, is sustainable, potentially cheap and environmentally friendly. Recent development in protein biochemistry and recombinant technology have facilitated the development of anti-parasite vaccine which in the past was impossible. One prerequisite for the anti-parasite-vaccine development is that the parasite has to ingest its host immunoglobulin. This study, therefore, was designed to determine whether Sarcoptes scabiei, a non blood-feeding parasite that resides on the avascular cornified layer of the skin, ingest its host immunoglobulin. Sections of routinely processed mites and skin from a mangy goat were probed with peroxidase-conjugated-anti-goat IgG and the immune complex was visualised with diaminobenzidine solution. To determine whether the ingested IgG was still intact or had been fragmented by the proteolytic enzymes, immunoblotting analysis of SDS-PAGE- fractionated proteins extracted from washed mites was performed. Quantification of IgG was done byan Elisa using purified goat IgG as control. This study showed that IgG in the mites confined to the mite’s gut only, and only a fraction of mite population ingested the IgG. The ingested IgG, as shown by immunoblot analysis, was mostly still intact. This study indicates that development of anti-scabies vaccines is reasonable.

  10. Immunoglobulin Concentration in Tears of Contact Lens Wearers

    Directory of Open Access Journals (Sweden)

    Rajendra P Maurya

    2014-01-01

    Conclusion: The relation of immunoglobulin concentration with increasing duration of wear and material of contact lens shows that tear immunoglobulin rise accrues due to mechanical stimulation, hence contact lenses should not be used for a long period and lenses of hard nature should be discouraged. The maintenance, cleaning and deproteinization of the lenses are of high importance to avoid immunostimulation.

  11. Vaccination with F1-V fusion protein protects black-footed ferrets (Mustela nigripes) against plague upon oral challenge with Yersinia pestis

    Science.gov (United States)

    Rocke, Tonie E.; Smith, Susan; Marinari, Paul E.; Kreeger, J.; Enama, J.T.; Powell, B.S.

    2008-01-01

    Previous studies have established that vaccination of black-footed ferrets (Mustela nigripes) with F1-V fusion protein by subcutaneous (SC) injection protects the animals against plague upon injection of the bacterium Yersinia pestis. This study demonstrates that the F1-V antigen can also protect ferrets against plague contracted via ingestion of a Y. pestis-infected mouse, a probable route for natural infection. Eight black-footed ferret kits were vaccinated with F1-V protein by SC injection at approximately 60 days-of-age. A booster vaccination was administered 3 mo later via SC injection. Four additional ferret kits received placebos. The animals were challenged 6 wk after the boost by feeding each one a Y. pestis-infected mouse. All eight vaccinates survived challenge, while the four controls succumbed to plague within 3 days after exposure. To determine the duration of antibody postvaccination, 18 additional black-footed ferret kits were vaccinated and boosted with F1-V by SC injection at 60 and 120 days-of-age. High titers to both F1 and V (mean reciprocal titers of 18,552 and 99,862, respectively) were found in all vaccinates up to 2 yr postvaccination, whereas seven control animals remained antibody negative throughout the same time period.

  12. Ferrets develop fatal influenza after inhaling small particle aerosols of highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1

    Directory of Open Access Journals (Sweden)

    Sosna William A

    2010-09-01

    Full Text Available Abstract Background There is limited knowledge about the potential routes for H5N1 influenza virus transmission to and between humans, and it is not clear whether humans can be infected through inhalation of aerosolized H5N1 virus particles. Ferrets are often used as a animal model for humans in influenza pathogenicity and transmissibility studies. In this manuscript, a nose-only bioaerosol inhalation exposure system that was recently developed and validated was used in an inhalation exposure study of aerosolized A/Vietnam/1203/2004 (H5N1 virus in ferrets. The clinical spectrum of influenza resulting from exposure to A/Vietnam/1203/2004 (H5N1 through intranasal verses inhalation routes was analyzed. Results Ferrets were successfully infected through intranasal instillation or through inhalation of small particle aerosols with four different doses of Influenza virus A/Vietnam/1203/2004 (H5N1. The animals developed severe influenza encephalomyelitis following intranasal or inhalation exposure to 101, 102, 103, or 104 infectious virus particles per ferret. Conclusions Aerosolized Influenza virus A/Vietnam/1203/2004 (H5N1 is highly infectious and lethal in ferrets. Clinical signs appeared earlier in animals infected through inhalation of aerosolized virus compared to those infected through intranasal instillation.

  13. Safety, immunogencity, and efficacy of a cold-adapted A/Ann Arbor/6/60 (H2N2) vaccine in mice and ferrets

    International Nuclear Information System (INIS)

    Chen, Grace L.; Lamirande, Elaine W.; Jin Hong; Kemble, George; Subbarao, Kanta

    2010-01-01

    We studied the attenuation, immunogenicity and efficacy of the cold-adapted A/Ann Arbor/6/60 (AA ca) (H2N2) virus in mice and ferrets to evaluate its use in the event of an H2 influenza pandemic. The AA ca virus was restricted in replication in the respiratory tract of mice and ferrets. In mice, 2 doses of vaccine elicited a > 4-fold rise in hemagglutination-inhibition (HAI) titer and resulted in complete inhibition of viral replication following lethal homologous wild-type virus challenge. In ferrets, a single dose of the vaccine elicited a > 4-fold rise in HAI titer and conferred complete protection against homologous wild-type virus challenge in the upper respiratory tract. In both mice and ferrets, the AA ca virus provided significant protection from challenge with heterologous H2 virus challenge in the respiratory tract. The AA ca vaccine is safe, immunogenic, and efficacious against homologous and heterologous challenge in mice and ferrets, supporting the evaluation of this vaccine in clinical trials.

  14. Vaccination with F1-V fusion protein protects black-footed ferrets (Mustela nigripes) against plague upon oral challenge with Yersinia pestis.

    Science.gov (United States)

    Rocke, Tonie E; Smith, Susan; Marinari, Paul; Kreeger, Julie; Enama, Jeffrey T; Powell, Bradford S

    2008-01-01

    Previous studies have established that vaccination of black-footed ferrets (Mustela nigripes) with F1-V fusion protein by subcutaneous (SC) injection protects the animals against plague upon injection of the bacterium Yersinia pestis. This study demonstrates that the F1-V antigen can also protect ferrets against plague contracted via ingestion of a Y. pestis-infected mouse, a probable route for natural infection. Eight black-footed ferret kits were vaccinated with F1-V protein by SC injection at approximately 60 days-of-age. A booster vaccination was administered 3 mo later via SC injection. Four additional ferret kits received placebos. The animals were challenged 6 wk after the boost by feeding each one a Y. pestis-infected mouse. All eight vaccinates survived challenge, while the four controls succumbed to plague within 3 days after exposure. To determine the duration of antibody postvaccination, 18 additional black-footed ferret kits were vaccinated and boosted with F1-V by SC injection at 60 and 120 days-of-age. High titers to both F1 and V (mean reciprocal titers of 18,552 and 99,862, respectively) were found in all vaccinates up to 2 yr postvaccination, whereas seven control animals remained antibody negative throughout the same time period.

  15. Different effects of salmeterol, formoterol and salbutamol on cholinergic responses in the ferret trachea.

    Science.gov (United States)

    Bergendal, A; Lindén, A; Lötvall, J; Skoogh, B E; Löfdahl, C G

    1995-04-01

    1. In the present study, the inhibitory effects of the selective beta 2-adrenoceptor agonists, salmeterol, formoterol and salbutamol, have been investigated on contractions of ferret trachea induced both by endogenous and exogenous acetylcholine. The aim of the study was to evaluate quantitative and/or qualitative differences in response which may indicate both pre- and post-junctional sites of action. The non-selective beta-antagonist, sotalol, was used to estimate beta-adrenoceptor involvement. 2. Isometric tension was measured in ferret isolated tracheal strips. The inhibitory effects of the drugs were studied on tonic contractions induced by pre-junctional activation with electrical field stimulation (EFS) (2 Hz, 700 mA) or post-junctional activation with exogenous acetylcholine (ACh) (0.5 microM, about EC80), giving a similar degree of smooth muscle response. 3. Concentration-response experiments were performed with formoterol (0.3 nM-0.3 microM) and salmeterol and salbutamol (10 nM-10 microM). The experiments ended with the addition of sotalol (10 microM). 4. All three beta-agonists inhibited the contractions in a concentration-dependent manner. Salbutamol, formoterol and salmeterol inhibited the EFS-induced contractions by 66(8)%, 105(5)% and 103(8)% (mean(s.e. mean)) respectively. ACh-induced contractions were inhibited by 37(6)%, 72(11)% and 33(8)%. Theophylline (10 nM-3 mM) inhibited the contractions to the same degree. 5. beta-Adrenoceptor blockade by sotalol significantly antagonized the inhibitory effects of salbutamol and formoterol on both EFS- and ACh-induced contractions. The effect of salmeterol on ACh-induced contraction was also significantly antagonized, whereas the inhibition of EFS-induced contraction was virtually unaffected. 6. In conclusion, salbutamol, salmeterol and formoterol produced greater inhibitory effects in preparations contracted by EFS than in preparations contracted by exogenously-added ACh. In the case of formoterol and

  16. Genomic structure and expression of immunoglobulins in Squamata.

    Science.gov (United States)

    Olivieri, David N; Garet, Elina; Estevez, Olivia; Sánchez-Espinel, Christian; Gambón-Deza, Francisco

    2016-04-01

    The Squamata order represents a major evolutionary reptile lineage, yet the structure and expression of immunoglobulins in this order has been scarcely studied in detail. From the genome sequences of four Squamata species (Gekko japonicus, Ophisaurus gracilis, Pogona vitticeps and Ophiophagus hannah) and RNA-seq datasets from 18 other Squamata species, we identified the immunoglobulins present in these animals as well as the tissues in which they are found. All Squamata have at least three immunoglobulin classes; namely, the immunoglobulins M, D, and Y. Unlike mammals, however, we provide evidence that some Squamata lineages possess more than one Cμ gene which is located downstream from the Cδ gene. The existence of two evolutionary lineages of immunoglobulin Y is shown. Additionally, it is demonstrated that while all Squamata species possess the λ light chain, only Iguanidae species possess the κ light chain. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Leucocytes, cytokines and satellite cells

    DEFF Research Database (Denmark)

    Paulsen, Gøran; Mikkelsen, Ulla Ramer; Raastad, Truls

    2012-01-01

    damage. With the exception of IL-6, the sources of systemic cytokines following exercise remain unclear The satellite cell response to severe muscle damage is related to regeneration, whereas the biological significance of satellite cell proliferation after mild damage or non-damaging exercise remains...

  18. Expression and distribution of voltage-gated ion channels in ferret sinoatrial node.

    Science.gov (United States)

    Brahmajothi, Mulugu V; Morales, Michael J; Campbell, Donald L; Steenbergen, Charles; Strauss, Harold C

    2010-10-01

    Spontaneous diastolic depolarization in the sinoatrial (SA) node enables it to serve as pacemaker of the heart. The variable cell morphology within the SA node predicts that ion channel expression would be heterogeneous and different from that in the atrium. To evaluate ion channel heterogeneity within the SA node, we used fluorescent in situ hybridization to examine ion channel expression in the ferret SA node region and atrial appendage. SA nodal cells were distinguished from surrounding cardiac myocytes by expression of the slow (SA node) and cardiac (surrounding tissue) forms of troponin I. Nerve cells in the sections were identified by detection of GAP-43 and cytoskeletal middle neurofilament. Transcript expression was characterized for the 4 hyperpolarization-activated cation channels, 6 voltage-gated Na(+) channels, 3 voltage-gated Ca(2+) channels, 24 voltage-gated K(+) channel α-subunits, and 3 ancillary subunits. To ensure that transcript expression was representative of protein expression, immunofluorescence was used to verify localization patterns of voltage-dependent K(+) channels. Colocalizations were performed to observe any preferential patterns. Some overlapping and nonoverlapping binding patterns were observed. Measurement of different cation channel transcripts showed heterogeneous expression with many different patterns of expression, attesting to the complexity of electrical activity in the SA node. This study provides insight into the possible role ion channel heterogeneity plays in SA node pacemaker activity.

  19. Single-unit Analysis of Somatosensory Processing in Core Auditory Cortex of Hearing Ferrets

    Science.gov (United States)

    Meredith, M. Alex; Allman, Brian L.

    2014-01-01

    The recent findings in several species that primary auditory cortex processes non-auditory information have largely overlooked the possibility for somatosensory effects. Therefore, the present investigation examined the core auditory cortices (anterior – AAF, and primary auditory-- A1, fields) for tactile responsivity. Multiple single-unit recordings from anesthetized ferret cortex yielded histologically verified neurons (n=311) tested with electronically controlled auditory, visual and tactile stimuli and their combinations. Of the auditory neurons tested, a small proportion (17%) was influenced by visual cues, but a somewhat larger number (23%) was affected by tactile stimulation. Tactile effects rarely occurred alone and spiking responses were observed in bimodal auditory-tactile neurons. However, the broadest tactile effect that was observed, which occurred in all neuron types, was that of suppression of the response to a concurrent auditory cue. The presence of tactile effects in core auditory cortices was supported by a substantial anatomical projection from the rostral suprasylvian sulcal somatosensory area. Collectively, these results demonstrate that crossmodal effects in auditory cortex are not exclusively visual and that somatosensation plays a significant role in modulation of acoustic processing and indicate that crossmodal plasticity following deafness may unmask these existing non-auditory functions. PMID:25728185

  20. Generation of a Live Attenuated Influenza Vaccine that Elicits Broad Protection in Mice and Ferrets.

    Science.gov (United States)

    Wang, Lulan; Liu, Su-Yang; Chen, Hsiang-Wen; Xu, Juan; Chapon, Maxime; Zhang, Tao; Zhou, Fan; Wang, Yao E; Quanquin, Natalie; Wang, Guiqin; Tian, Xiaoli; He, Zhanlong; Liu, Longding; Yu, Wenhai; Sanchez, David Jesse; Liang, Yuying; Jiang, Taijiao; Modlin, Robert; Bloom, Barry R; Li, Qihan; Deng, Jane C; Zhou, Paul; Qin, F Xiao-Feng; Cheng, Genhong

    2017-03-08

    New influenza vaccines that provide effective and broad protection are desperately needed. Live attenuated viruses are attractive vaccine candidates because they can elicit both humoral and cellular immune responses. However, recent formulations of live attenuated influenza vaccines (LAIVs) have not been protective. We combined high-coverage transposon mutagenesis of influenza virus with a rapid high-throughput screening for attenuation to generate W7-791, a live attenuated mutant virus strain. W7-791 produced only a transient asymptomatic infection in adult and neonatal mice even at doses 100-fold higher than the LD 50 of the parent strain. A single administration of W7-791 conferred full protection to mice against lethal challenge with H1N1, H3N2, and H5N1 strains, and improved viral clearance in ferrets. Adoptive transfer of T cells from W7-791-immunized mice conferred heterologous protection, indicating a role for T cell-mediated immunity. These studies present an LAIV development strategy to rapidly generate and screen entire libraries of viral clones. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Indigenous Wildlife Rabies in Taiwan: Ferret Badgers, a Long Term Terrestrial Reservoir.

    Science.gov (United States)

    Lan, Yu-Ching; Wen, Tzai-Hung; Chang, Chao-Chin; Liu, Hsin-Fu; Lee, Pei-Fen; Huang, Chung-Yuan; Chomel, Bruno B; Chen, Yi-Ming A

    2017-01-01

    The emerging disease of rabies was confirmed in Taiwan ferret badgers (FBs) and reported to the World Organization for Animal Health (OIE) on July 17, 2013. The spread of wildlife rabies can be related to neighborhood countries in Asia. The phylogenetic analysis was conducted by maximum likelihood (ML) methods and the Bayesian coalescent approach based on the glycoprotein (G) and nucleoprotein (N) genes. The phylogeographic and spatial temporal dynamics of viral transmission were determined by using SPREAD, QGIS. Therefore, the origin and the change with time of the viruses can be identified. Results showed the rabies virus of FB strains in Taiwan is a unique clade among other strains in Asia. According to the phylogeographic coalescent tree, three major genotypes of the FB rabies virus have circulated in three different geographical areas in Taiwan. Two genotypes have distributed into central and southern Taiwan between two ecological river barriers. The third genotype has been limited in southeastern Taiwan by the natural mountain barrier. The diversity of FB rabies viruses indicates that the biological profile of FBs could vary in different geographical areas in Taiwan. An enhanced surveillance system needs to be established near the currently identified natural barriers for early warnings of the rabies virus outbreak in Taiwan.

  2. Indigenous Wildlife Rabies in Taiwan: Ferret Badgers, a Long Term Terrestrial Reservoir

    Directory of Open Access Journals (Sweden)

    Yu-Ching Lan

    2017-01-01

    Full Text Available The emerging disease of rabies was confirmed in Taiwan ferret badgers (FBs and reported to the World Organization for Animal Health (OIE on July 17, 2013. The spread of wildlife rabies can be related to neighborhood countries in Asia. The phylogenetic analysis was conducted by maximum likelihood (ML methods and the Bayesian coalescent approach based on the glycoprotein (G and nucleoprotein (N genes. The phylogeographic and spatial temporal dynamics of viral transmission were determined by using SPREAD, QGIS. Therefore, the origin and the change with time of the viruses can be identified. Results showed the rabies virus of FB strains in Taiwan is a unique clade among other strains in Asia. According to the phylogeographic coalescent tree, three major genotypes of the FB rabies virus have circulated in three different geographical areas in Taiwan. Two genotypes have distributed into central and southern Taiwan between two ecological river barriers. The third genotype has been limited in southeastern Taiwan by the natural mountain barrier. The diversity of FB rabies viruses indicates that the biological profile of FBs could vary in different geographical areas in Taiwan. An enhanced surveillance system needs to be established near the currently identified natural barriers for early warnings of the rabies virus outbreak in Taiwan.

  3. Eyedrop Vaccination Induced Systemic and Mucosal Immunity against Influenza Virus in Ferrets.

    Directory of Open Access Journals (Sweden)

    Sangchul Yoon

    Full Text Available We investigated eyedrop vaccination (EDV in pre-clinical development for immunological protection against influenza and for potential side effects involving ocular inflammation and the central nervous system (CNS. Live attenuated influenza EDV, CA07 (H1N1, PZ-4 (H1N2 and Uruguay (H3N2, induced both systemic and mucosal virus-specific antibody responses in ferrets. In addition, EDV resulted in a clinically significant protection against viral challenge, and suppression of viral replication in nasal secretion and lung tissue. Regarding safety, we found that administered EDV flow through the tear duct to reach the base of nasal cavity, and thus do not contact the olfactory bulb. All analyses for potential adverse effects due to EDV, including histological and functional examinations, did not reveal significant side effects. On the basis of these findings, we propose that EDV as effective, while being a safe administration route with minimum local side effects, CNS invasion, or visual function disturbance.

  4. CAF01 potentiates immune responses and efficacy of an inactivated influenza vaccine in ferrets.

    Directory of Open Access Journals (Sweden)

    Cyril Jean-Marie Martel

    Full Text Available Trivalent inactivated vaccines (TIV against influenza are given to 350 million people every year. Most of these are non-adjuvanted vaccines whose immunogenicity and protective efficacy are considered suboptimal. Commercially available non-adjuvanted TIV are known to elicit mainly a humoral immune response, whereas the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6'-dibehenate, CAF01 was developed. CAF01 has proven to enhance both humoral and cell-mediated immune responses to a number of different experimental vaccine candidates. In this study, we compared the immune responses in ferrets to a commercially available TIV with the responses to the same vaccine mixed with the CAF01 adjuvant. Two recently circulating H1N1 viruses were used as challenge to test the vaccine efficacy. CAF01 improved the immunogenicity of the vaccine, with increased influenza-specific IgA and IgG levels. Additionally, CAF01 promoted cellular-mediated immunity as indicated by interferon-gamma expressing lymphocytes, measured by flow cytometry. CAF01 also enhanced the protection conferred by the vaccine by reducing the viral load measured in nasal washes by RT-PCR. Finally, CAF01 allowed for dose-reduction and led to higher levels of protection compared to TIV adjuvanted with a squalene emulsion. The data obtained in this human-relevant challenge model supports the potential of CAF01 in future influenza vaccines.

  5. Auditory and visual interactions between the superior and inferior colliculi in the ferret.

    Science.gov (United States)

    Stitt, Iain; Galindo-Leon, Edgar; Pieper, Florian; Hollensteiner, Karl J; Engler, Gerhard; Engel, Andreas K

    2015-05-01

    The integration of visual and auditory spatial information is important for building an accurate perception of the external world, but the fundamental mechanisms governing such audiovisual interaction have only partially been resolved. The earliest interface between auditory and visual processing pathways is in the midbrain, where the superior (SC) and inferior colliculi (IC) are reciprocally connected in an audiovisual loop. Here, we investigate the mechanisms of audiovisual interaction in the midbrain by recording neural signals from the SC and IC simultaneously in anesthetized ferrets. Visual stimuli reliably produced band-limited phase locking of IC local field potentials (LFPs) in two distinct frequency bands: 6-10 and 15-30 Hz. These visual LFP responses co-localized with robust auditory responses that were characteristic of the IC. Imaginary coherence analysis confirmed that visual responses in the IC were not volume-conducted signals from the neighboring SC. Visual responses in the IC occurred later than retinally driven superficial SC layers and earlier than deep SC layers that receive indirect visual inputs, suggesting that retinal inputs do not drive visually evoked responses in the IC. In addition, SC and IC recording sites with overlapping visual spatial receptive fields displayed stronger functional connectivity than sites with separate receptive fields, indicating that visual spatial maps are aligned across both midbrain structures. Reciprocal coupling between the IC and SC therefore probably serves the dynamic integration of visual and auditory representations of space. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  6. Interference of immunoglobulins in two glucagon radioimmunoassays

    International Nuclear Information System (INIS)

    Von Schenck, H.; Grubb, A.O.

    1982-01-01

    Radioimmunoassays of glucagon in plasma may be complicated by interaction with other substances of high molecular mass. Precipitates of such substances with ammonium sulfate showed, after isoelectric focusing, two fractions having glucagon immunoreactivity. One fraction (pI approx.10) evidently is associated with the Fc portion (but not the Fab portion) of purified polyclonal immunoglobulin G (IgG). Equal amounts of purified monoclonal IgG of various subclasses, especially IgG 1, gave different ''glucagon'' readings, suggesting that some IgG may interfere more strongly than others. The other fraction (pI 5-6) appeared less consistently, and on gel chromatography appeared to be slightly larger than IgG. Together these fractions add about 50-100 ng/L to the immunoreactive glucagon values in plasma. Therefore methods in which glucagon is extracted before assay should be used for determining the concentration of glucagon present physiologically

  7. Intravenous immunoglobulin, pharmacogenomics, and Kawasaki disease.

    Science.gov (United States)

    Kuo, Ho-Chang; Hsu, Yu-Wen; Wu, Mei-Shin; Chien, Shu-Chen; Liu, Shih-Feng; Chang, Wei-Chiao

    2016-02-01

    Kawasaki disease (KD) is a systemic vasculitis of unknown etiology and it is therefore worth examining the multifactorial interaction of genes and environmental factors. Targeted genetic association and genome-wide association studies have helped to provide a better understanding of KD from infection to the immune-related response. Findings in the past decade have contributed to a major breakthrough in the genetics of KD, with the identification of several genomic regions linked to the pathogenesis of KD, including ITPKC, CD40, BLK, and FCGR2A. This review focuses on the factors associated with the genetic polymorphisms of KD and the pharmacogenomics of the response to treatment in patients with intravenous immunoglobulin resistance. Copyright © 2014. Published by Elsevier B.V.

  8. Solar urticaria successfully treated with intravenous immunoglobulin.

    LENUS (Irish Health Repository)

    Hughes, R

    2012-02-01

    Idiopathic solar urticaria (SU) is a rare, debilitating photodermatosis, which may be difficult to treat. First-line treatment with antihistamines is effective in mild cases, but remission after phototherapeutic induction of tolerance is often short-lived. Other treatment options include plasma exchange, photopheresis and cyclosporin. We present two cases of severe, idiopathic SU, which were resistant to conventional treatment. Both patients achieved remission after administration of intravenous immunoglobulin (IVIg) and have remained in remission at 13 months and 4 years, respectively. There are only two case reports of successful treatment of solar urticaria with IVIg. In our experience IVIg given at a total dose of 2 g\\/kg over several 5-day courses about a month apart is an effective treatment option for severe idiopathic SU. It is also generally safe, even if certainly subject to significant theoretical risks, such as induction of viral infection or anaphylaxis.

  9. Structural repertoire of immunoglobulin λ light chains

    KAUST Repository

    Chailyan, Anna

    2011-03-01

    The immunoglobulin λ isotype is present in nearly all vertebrates and plays an important role in the human immune system. Despite its importance, few systematic studies have been performed to analyze the structural conformation of its variable regions, contrary to what is the case for κ and heavy chains. We show here that an analysis of the structures of λ chains allows the definition of a discrete set of recurring conformations (canonical structures) of their hypervariable loops and, most importantly, the identification of sequence constraints that can be used to predict their structure. We also show that the structural repertoire of λ chains is different and more varied than that of the κ chains, consistently with the current view of the involvement of the two major light-chain families in complementary strategies of the immune system to ensure a fine tuning between diversity and stability in antigen recognition. © 2011 Wiley-Liss, Inc.

  10. Cytokine Correlations in Youth with Tic Disorders

    OpenAIRE

    Parker-Athill, E. Carla; Ehrhart, Jared; Tan, Jun; Murphy, Tanya K.

    2015-01-01

    Background: Studies have noted immunological disruptions in patients with tic disorders, including increased serum cytokine levels. This study aimed to determine whether or not cytokine levels could be correlated with tic symptom severity in patients with a diagnosed tic disorder.

  11. Cytokines and mood in healthy young adults

    NARCIS (Netherlands)

    Jansen, J.; Fernstrand, A.M.; Van De Loo, A.J.A.E.; Garssen, J.; Verster, J.C.

    2015-01-01

    Purpose: A link between chronic inflammation and neuropsychiatric disorders has been demonstrated previously. For example, pro- and anti-inflammatory cytokines have shown to impact neurocircuits relevant to mood regulation. Elevated levels of inflammatory cytokines have been associated with the

  12. Elicitation of Protective Antibodies against a Broad Panel of H1N1 Viruses in Ferrets Preimmune to Historical H1N1 Influenza Viruses.

    Science.gov (United States)

    Carter, Donald M; Darby, Christopher A; Johnson, Scott K; Carlock, Michael A; Kirchenbaum, Greg A; Allen, James D; Vogel, Thorsten U; Delagrave, Simon; DiNapoli, Joshua; Kleanthous, Harold; Ross, Ted M

    2017-12-15

    Most preclinical animal studies test influenza vaccines in immunologically naive animal models, even though the results of vaccination may not accurately reflect the effectiveness of vaccine candidates in humans that have preexisting immunity to influenza. In this study, novel, broadly reactive influenza vaccine candidates were assessed in preimmune ferrets. These animals were infected with different H1N1 isolates before being vaccinated or infected with another influenza virus. Previously, our group has described the design and characterization of computationally optimized broadly reactive hemagglutinin (HA) antigens (COBRA) for H1N1 isolates. Vaccinating ferrets with virus-like particle (VLP) vaccines expressing COBRA HA proteins elicited antibodies with hemagglutination inhibition (HAI) activity against more H1N1 viruses in the panel than VLP vaccines expressing wild-type HA proteins. Specifically, ferrets infected with the 1986 virus and vaccinated with a single dose of the COBRA HA VLP vaccines elicited antibodies with HAI activity against 11 to 14 of the 15 H1N1 viruses isolated between 1934 and 2013. A subset of ferrets was infected with influenza viruses expressing the COBRA HA antigens. These COBRA preimmune ferrets had superior breadth of HAI activity after vaccination with COBRA HA VLP vaccines than COBRA preimmune ferrets vaccinated with VLP vaccines expressing wild-type HA proteins. Overall, priming naive ferrets with COBRA HA based viruses or using COBRA HA based vaccines to boost preexisting antibodies induced by wild-type H1N1 viruses, COBRA HA antigens elicited sera with the broadest HAI reactivity against multiple antigenic H1N1 viral variants. This is the first report demonstrating the effectiveness of a broadly reactive or universal influenza vaccine in a preimmune ferret model. IMPORTANCE Currently, many groups are testing influenza vaccine candidates to meet the challenge of developing a vaccine that elicits broadly reactive and long

  13. Avian cytokines in health and disease

    Directory of Open Access Journals (Sweden)

    Wigley P

    2003-01-01

    Full Text Available Cytokines are proteins secreted by cells that play an important role in the activation and regulation of other cells and tissues during inflammation and immune responses. Although well described in several mammalian species, the role of cytokines and other related proteins is poorly understood in avian species. Recent advances in avian genetics and immunology have begun to allow the exploration of cytokines in health and disease. Cytokines may be classified in a number of ways, but may be conveniently arranged into four broad groups on the basis of their function. Proinflammatory cytokines such as interleukin-6 and interleukin-1beta play a role in mediating inflammation during disease or injury. Th1 cytokines, including interleukin-12 and interferon-gamma, are involved in the induction of cell-mediated immunity, whereas Th2 cytokines such as interleukin-4 are involved in the induction of humoral immunity. The final group Th3 or Tr cytokines play a role in regulation of immunity. The role of various cytokines in infectious and non-infectious diseases of chickens and turkeys is now being investigated. Although there are only a few reliable ELISAs or bioassays developed for avian cytokines, the use of molecular techniques, and in particular quantitative RT-PCR (Taqman has allowed investigation of cytokine responses in a number of diseases including salmonellosis, coccidiosis and autoimmune thyroiditis. In addition the use of recombinant cytokines as therapeutic agents or as vaccine adjuvants is now being explored.

  14. Cytokine determinants of viral tropism

    Science.gov (United States)

    McFadden, Grant; Mohamed, Mohamed R.; Rahman, Masmudur M.; Bartee, Eric

    2015-01-01

    The specificity of a given virus for a ceil type, tissue or species — collectively known as viral tropism — is an important factor in determining the outcome of viral infection in any particular host. Owing to the increased prevalence of zoonotic infections and the threat of emerging and re-emerging pathogens, gaining a better understanding of the factors that determine viral tropism has become particularly important. In this Review, we summarize our current understanding of the central role of antiviral and pro-inflammatory cytokines, particularly the interferons and tumour necrosis factor, in dictating viral tropism and how these cytokine pathways can be exploited therapeutically for cancer treatment and to better counter future threats from emerging zoonotic pathogens. PMID:19696766

  15. Subcutaneous versus intravenous immunoglobulin in multifocal motor neuropathy

    DEFF Research Database (Denmark)

    Harbo, T; Andersen, Henning; Hess, A

    2009-01-01

    Background and purpose: For treatment of multifocal motor neuropathy (MMN), we hypothesized that (i) infusion of equivalent dosages of subcutaneous immunoglobulin (SCIG) is as effective as intravenous immunoglobulin (IVIG) and that (ii) subcutaneous infusion at home is associated with a better...... at the injection sites for a few weeks. All other adverse effects during SCIG were mild and transient. No differences between treatments of health-related quality of life occurred. Conclusion: In MMN, short-term subcutaneous infusion of immunoglobulin is feasible, safe and as effective as intravenous infusion...

  16. Acute Inflammatory Demyelinating Neuropathy : Immunoglobulin And Immune Complex Profile

    Directory of Open Access Journals (Sweden)

    Shripad A

    2003-01-01

    Full Text Available Serum immunoglobulins (IgG, IgA and IgM and immune complexes IgG (IcG were measured in 58 cases of acute inflammatory demyelinating neuropathy, popularly known as Guillian Barre′ syndrome, and in 30 healthy controls using single radial immunodiffusion assay. Immunoglobulin and immune complex levels were significantly elevated in patients as compared to controls. The increased levels of immunoglobulins and immune complexes may contribute to the pathogenesis of the disease and provide rationale for therapeutic plasmapheresis.

  17. H5N1 vaccine-specific B cell responses in ferrets primed with live attenuated seasonal influenza vaccines.

    Directory of Open Access Journals (Sweden)

    Xing Cheng

    Full Text Available Live attenuated influenza H5N1 vaccines have been produced and evaluated in mice and ferrets that were never exposed to influenza A virus infection (Suguitan et al., Plos Medicine, e360:1541, 2006. However, the preexisting influenza heterosubtypic immunity on live attenuated H5N1 vaccine induced immune response has not been evaluated.Primary and recall B cell responses to live attenuated H5N1 vaccine viruses were examined using a sensitive antigen-specific B cell ELISpot assay to investigate the effect of preexisting heterosubtypic influenza immunity on the development of H5N1-specific B cell immune responses in ferrets. Live attenuated H5N1 A/Hong Kong/213/03 and A/Vietnam/1203/04 vaccine viruses induced measurable H5-specific IgM and IgG secreting B cells after intranasal vaccination. However, H5-specific IgG secreting cells were detected significantly earlier and at a greater frequency after H5N1 inoculation in ferrets previously primed with trivalent live attenuated influenza (H1N1, H3N2 and B vaccine. Priming studies further revealed that the more rapid B cell responses to H5 resulted from cross-reactive B cell immunity to the hemagglutinin H1 protein. Moreover, vaccination with the H1N1 vaccine virus was able to induce protective responses capable of limiting replication of the H5N1 vaccine virus to a level comparable with prior vaccination with the H5N1 vaccine virus without affecting H5N1 vaccine virus induced antibody response.The findings indicate that previous vaccination with seasonal influenza vaccine may accelerate onset of immunity by an H5N1 ca vaccine and the heterosubtypic immunity may be beneficial for pandemic preparedness.

  18. Low pathogenic avian influenza isolates from wild birds replicate and transmit via contact in ferrets without prior adaptation.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Driskell

    Full Text Available Direct transmission of avian influenza viruses to mammals has become an increasingly investigated topic during the past decade; however, isolates that have been primarily investigated are typically ones originating from human or poultry outbreaks. Currently there is minimal comparative information on the behavior of the innumerable viruses that exist in the natural wild bird host. We have previously demonstrated the capacity of numerous North American avian influenza viruses isolated from wild birds to infect and induce lesions in the respiratory tract of mice. In this study, two isolates from shorebirds that were previously examined in mice (H1N9 and H6N1 subtypes are further examined through experimental inoculations in the ferret with analysis of viral shedding, histopathology, and antigen localization via immunohistochemistry to elucidate pathogenicity and transmission of these viruses. Using sequence analysis and glycan binding analysis, we show that these avian viruses have the typical avian influenza binding pattern, with affinity for cell glycoproteins/glycolipids having terminal sialic acid (SA residues with α 2,3 linkage [Neu5Ac(α2,3Gal]. Despite the lack of α2,6 linked SA binding, these AIVs productively infected both the upper and lower respiratory tract of ferrets, resulting in nasal viral shedding and pulmonary lesions with minimal morbidity. Moreover, we show that one of the viruses is able to transmit to ferrets via direct contact, despite its binding affinity for α 2,3 linked SA residues. These results demonstrate that avian influenza viruses, which are endemic in aquatic birds, can potentially infect humans and other mammals without adaptation. Finally this work highlights the need for additional study of the wild bird subset of influenza viruses in regard to surveillance, transmission, and potential for reassortment, as they have zoonotic potential.

  19. Cloned defective interfering influenza virus protects ferrets from pandemic 2009 influenza A virus and allows protective immunity to be established.

    Directory of Open Access Journals (Sweden)

    Nigel J Dimmock

    Full Text Available Influenza A viruses are a major cause of morbidity and mortality in the human population, causing epidemics in the winter, and occasional worldwide pandemics. In addition there are periodic outbreaks in domestic poultry, horses, pigs, dogs, and cats. Infections of domestic birds can be fatal for the birds and their human contacts. Control in man operates through vaccines and antivirals, but both have their limitations. In the search for an alternative treatment we have focussed on defective interfering (DI influenza A virus. Such a DI virus is superficially indistinguishable from a normal virus but has a large deletion in one of the eight RNAs that make up the viral genome. Antiviral activity resides in the deleted RNA. We have cloned one such highly active DI RNA derived from segment 1 (244 DI virus and shown earlier that intranasal administration protects mice from lethal disease caused by a number of different influenza A viruses. A more cogent model of human influenza is the ferret. Here we found that intranasal treatment with a single dose of 2 or 0.2 µg 244 RNA delivered as A/PR/8/34 virus particles protected ferrets from disease caused by pandemic virus A/California/04/09 (A/Cal; H1N1. Specifically, 244 DI virus significantly reduced fever, weight loss, respiratory symptoms, and infectious load. 244 DI RNA, the active principle, was amplified in nasal washes following infection with A/Cal, consistent with its amelioration of clinical disease. Animals that were treated with 244 DI RNA cleared infectious and DI viruses without delay. Despite the attenuation of infection and disease by DI virus, ferrets formed high levels of A/Cal-specific serum haemagglutination-inhibiting antibodies and were solidly immune to rechallenge with A/Cal. Together with earlier data from mouse studies, we conclude that 244 DI virus is a highly effective antiviral with activity potentially against all influenza A subtypes.

  20. H1N1 influenza viruses varying widely in hemagglutinin stability transmit efficiently from swine to swine and to ferrets.

    Directory of Open Access Journals (Sweden)

    Marion Russier

    2017-03-01

    Full Text Available A pandemic-capable influenza virus requires a hemagglutinin (HA surface glycoprotein that is immunologically unseen by most people and is capable of supporting replication and transmission in humans. HA stabilization has been linked to 2009 pH1N1 pandemic potential in humans and H5N1 airborne transmissibility in the ferret model. Swine have served as an intermediate host for zoonotic influenza viruses, yet the evolutionary pressure exerted by this host on HA stability was unknown. For over 70 contemporary swine H1 and H3 isolates, we measured HA activation pH to range from pH 5.1 to 5.9 for H1 viruses and pH 5.3 to 5.8 for H3 viruses. Thus, contemporary swine isolates vary widely in HA stability, having values favored by both avian (pH >5.5 and human and ferret (pH ≤5.5 species. Using an early 2009 pandemic H1N1 (pH1N1 virus backbone, we generated three viruses differing by one HA residue that only altered HA stability: WT (pH 5.5, HA1-Y17H (pH 6.0, and HA2-R106K (pH 5.3. All three replicated in pigs and transmitted from pig-to-pig and pig-to-ferret. WT and R106 viruses maintained HA genotype and phenotype after transmission. Y17H (pH 6.0 acquired HA mutations that stabilized the HA protein to pH 5.8 after transmission to pigs and 5.5 after transmission to ferrets. Overall, we found swine support a broad range of HA activation pH for contact transmission and many recent swine H1N1 and H3N2 isolates have stabilized (human-like HA proteins. This constitutes a heightened pandemic risk and underscores the importance of ongoing surveillance and control efforts for swine viruses.

  1. Rare and new cumaceans (Crustacea, Peracarida from the southern margin of the Cap Ferret Canyon (Bay of Biscay

    Directory of Open Access Journals (Sweden)

    Jordi Corbera

    2012-10-01

    Full Text Available A new cumacean genus and species, Ithyleucon sorbei gen. et sp. n., was described from material collected in the southern margin of the Cap Ferret Canyon (Bay of Biscay, NE Atlantic. Although the new genus resembles Pseudoleucon Zimmer, 1903, in terms of the general aspect of the carapace and the pseudo-rostrum position, it shows important differences in the uropod structure and in the size of the antenna 1 accessory flagellum. In addition, some comments regarding the morphology of certain rare species (Mesolamprops denticulatus Ledoyer, 1983, Hemilamprops normani Bonnier, 1896 and Schizocuma spino-culatum (Jones, 1984 are also provided.

  2. The interleukin (IL)-1 cytokine family--Balance between agonists and antagonists in inflammatory diseases.

    Science.gov (United States)

    Palomo, Jennifer; Dietrich, Damien; Martin, Praxedis; Palmer, Gaby; Gabay, Cem

    2015-11-01

    The interleukin (IL)-1 family of cytokines comprises 11 members, including 7 pro-inflammatory agonists (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β, IL-36γ) and 4 defined or putative antagonists (IL-1R antagonist (IL-1Ra), IL-36Ra, IL-37, and IL-38) exerting anti-inflammatory activities. Except for IL-1Ra, IL-1 cytokines do not possess a leader sequence and are secreted via an unconventional pathway. In addition, IL-1β and IL-18 are produced as biologically inert pro-peptides that require cleavage by caspase-1 in their N-terminal region to generate active proteins. N-terminal processing is also required for full activity of IL-36 cytokines. The IL-1 receptor (IL-1R) family comprises 10 members and includes cytokine-specific receptors, co-receptors and inhibitory receptors. The signaling IL-1Rs share a common structure with three extracellular immunoglobulin (Ig) domains and an intracellular Toll-like/IL-1R (TIR) domain. IL-1 cytokines bind to their specific receptor, which leads to the recruitment of a co-receptor and intracellular signaling. IL-1 cytokines induce potent inflammatory responses and their activity is tightly controlled at the level of production, protein processing and maturation, receptor binding and post-receptor signaling by naturally occurring inhibitors. Some of these inhibitors are IL-1 family antagonists, while others are IL-1R family members acting as membrane-bound or soluble decoy receptors. An imbalance between agonist and antagonist levels can lead to exaggerated inflammatory responses. Several genetic modifications or mutations associated with dysregulated IL-1 activity and autoinflammatory disorders were identified in mouse models and in patients. These findings paved the road to the successful use of IL-1 inhibitors in diseases that were previously considered as untreatable. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Immunoglobulin for alloimmune hemolytic disease in neonates.

    Science.gov (United States)

    Zwiers, Carolien; Scheffer-Rath, Mirjam Ea; Lopriore, Enrico; de Haas, Masja; Liley, Helen G

    2018-03-18

    Exchange transfusion and phototherapy have traditionally been used to treat jaundice and avoid the associated neurological complications. Because of the risks and burdens of exchange transfusion, intravenous immunoglobulin (IVIg) has been suggested as an alternative therapy for alloimmune hemolytic disease of the newborn (HDN) to reduce the need for exchange transfusion. To assess the effect and complications of IVIg in newborn infants with alloimmune HDN on the need for and number of exchange transfusions. We performed electronic searches of CENTRAL, PubMed, Embase (Ovid), Web of Science, CINAHL (EBSCOhost), Academic Search Premier, and the trial registers ClinicalTrials.gov and controlled-trials.com in May 2017. We also searched reference lists of included and excluded trials and relevant reviews for further relevant studies. We considered all randomized and quasi-randomized controlled trials of IVIg in the treatment of alloimmune HDN. Trials must have used predefined criteria for the use of IVIg and exchange transfusion therapy to be included. We used the standard methods of Cochrane and its Neonatal Review Group. We assessed studies for inclusion and two review authors independently assessed quality and extracted data. We discussed any differences of opinion to reach consensus. We contacted investigators for additional or missing information. We calculated risk ratio (RR), risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) for categorical outcomes. We calculated mean difference (MD) for continuous variables. We used GRADE criteria to assess the risk of bias for major outcomes and to summarize the level of evidence. Nine studies with 658 infants fulfilled the inclusion criteria. Term and preterm infants with Rh or ABO (or both) incompatibility were included. The use of exchange transfusion decreased significantly in the immunoglobulin treated group (typical RR 0.35, 95% CI 0.25 to 0.49; typical RD -0.22, 95% CI -0.27 to

  4. The role of cytokine deficiencies and cytokine autoantibodies in clinical dermatology

    DEFF Research Database (Denmark)

    Liszewski, Walter; Gniadecki, Robert

    2016-01-01

    Cytokines are small, secreted proteins that are essential for promoting and maintaining a normal immune response. Upregulation of cytokines frequently occurs in autoimmune and inflammatory diseases. Conversely, several immunodeficiency, autoimmune and autoinflammatory disorders are known to occur...... review the role of cytokine deficiencies and cytokine autoantibodies in immunodeficiency syndromes, as well as in autoimmune disorders. Finally, we will examine autoinflammatory disorders due to cytokine deficiencies....

  5. Detection of dentin antigenic fractions by salivary immunoglobulin G ...

    African Journals Online (AJOL)

    Detection of dentin antigenic fractions by salivary immunoglobulin G in patients undergoing orthodontic treatment. TMP Soares da Costa, S de Paula Ramos, MM Hidalgo, A Consolaro, SA Khan, EN Itano ...

  6. Immunoglobulins in granular corneal dystrophy Groenouw type I

    DEFF Research Database (Denmark)

    Møller, H U; Bojsen-Møller, M; Schrøder, H D

    1993-01-01

    Three patients with granular corneal dystrophy Groenouw type I underwent corneal grafting, and cryostat sections of the corneal buttons were examined immunohistochemically for immunoglobulins. Positive results were obtained for IgG, Kappa-, and Lambda chains with immunofluorescence technique...

  7. Human placental immunoglobulins show unique re-association ...

    African Journals Online (AJOL)

    Objective: To study re-association pattern of human placental eluate immunoglobulins with acid treated isologous and third party trophoblast derived placental microvesicles. Design: Laboratory based experimentation. Setting: Biological Sciences Department and Discipline for Reproductive Medicine University of ...

  8. Immunoglobulin G antisperm antibodies and prediction of spontaneous pregnancy

    NARCIS (Netherlands)

    Leushuis, Esther; van der Steeg, Jan Willem; Steures, Pieternel; Repping, Sjoerd; Schöls, Willem; van der Veen, Fulco; Mol, Ben Willem J.; Hompes, Peter G. A.

    2009-01-01

    Objective: To investigate the predictive capacity of immunoglobulin G ASA (direct MAR test) for spontaneous ongoing pregnancy in subfertile couples. Design: Prospective cohort study. Setting: Nine fertility centers in The Netherlands. Patient(s): Consecutive ovulatory subfertile couples.

  9. Beneficial use of immunoglobulins in the treatment of Sydenham chorea

    NARCIS (Netherlands)

    T.D. van Immerzeel (Tabitha); R.M. van Gilst (Ruud); N.G. Hartwig (Nico)

    2010-01-01

    textabstractThis double case report indicates that treatment with intravenous immunoglobulins (IVIG) is effective in patients with Sydenham chorea (SC). SC is a rare but impressive clinical manifestation following streptococcal infection. This movement disorder characterised by chorea, emotional

  10. Spirulina ameliorates methotrexate hepatotoxicity via antioxidant, immune stimulation, and proinflammatory cytokines and apoptotic proteins modulation.

    Science.gov (United States)

    Khafaga, Asmaa F; El-Sayed, Yasser S

    2018-03-01

    Methotrexate (MTX) is an efficient cytotoxic drug used against various carcinogenic, inflammatory and autoimmune diseases; however, the hepatotoxicity of MTX limits its use. Therefore, the present study aimed to evaluate the potential hepatoprotective and immune-stimulant effect of Spirulina platensis (SP) against MTX acute toxicity. Thirty-two male Wistar rats were randomly allocated into the following four groups (n = 8): control, SP (500 mg/kg bwt, oral gavage daily for 21 days), MTX (20 mg/kg bwt, single ip injection), and MTX+SP. Hepatic and splenic histoarchitecture, leukocyte counts and serum immunoglobulins were evaluated. Hepatic oxidant/antioxidant status, proinflammatory cytokines (tumor necrosis factor-α, and interleukin 6), and pro-apoptotic proteins (caspase 3 and Bax) immunoexpression were assessed. MTX induced extensive hepatic necrosis and vacuolation, and sever lymphoid depletion in splenic white pulp with increased levels of serum transaminases, lactate dehydrogenase, and hepatic malondialdehyde, tumor necrosis factor-α and interleukin 6; and number of caspase 3- and Bax-positive hepatocytes. A significant decrease in leukocyte counts, serum immunoglobulins (IgA, IgM and IgG) level, and hepatic antioxidant enzymes (GSH, GPx, SOD, and CAT) was also detected. Pretreatment with SP resulted in significant improvements in hepatic and splenic histologic architecture, as well as restoring liver enzymes and reduction of lipid peroxidation product, proinflammatory cytokines, and caspase 3 and Bax immunoexpression. Additionally, a significant increase in antioxidant enzymes, serum immunoglobulins, and total leukocyte counts was demonstrated. SP possesses promising antioxidant, anti-inflammatory, anti-apoptotic and immune stimulatory properties against MTX-induced hepatotoxicity and immunosuppression. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. New class of monoclonal antibodies against severe influenza: prophylactic and therapeutic efficacy in ferrets.

    Directory of Open Access Journals (Sweden)

    Robert H E Friesen

    2010-02-01

    Full Text Available The urgent medical need for innovative approaches to control influenza is emphasized by the widespread resistance of circulating subtype H1N1 viruses to the leading antiviral drug oseltamivir, the pandemic threat posed by the occurrences of human infections with highly pathogenic avian H5N1 viruses, and indeed the evolving swine-origin H1N1 influenza pandemic. A recently discovered class of human monoclonal antibodies with the ability to neutralize a broad spectrum of influenza viruses (including H1, H2, H5, H6 and H9 subtypes has the potential to prevent and treat influenza in humans. Here we report the latest efficacy data for a representative antibody of this novel class.We evaluated the prophylactic and therapeutic efficacy of the human monoclonal antibody CR6261 against lethal challenge with the highly pathogenic avian H5N1 virus in ferrets, the optimal model of human influenza infection. Survival rates, clinically relevant disease signs such as changes in body weight and temperature, virus replication in lungs and upper respiratory tract, as well as macro- and microscopic pathology were investigated. Prophylactic administration of 30 and 10 mg/kg CR6261 prior to viral challenge completely prevented mortality, weight loss and reduced the amount of infectious virus in the lungs by more than 99.9%, abolished shedding of virus in pharyngeal secretions and largely prevented H5N1-induced lung pathology. When administered therapeutically 1 day after challenge, 30 mg/kg CR6261 prevented death in all animals and blunted disease, as evidenced by decreased weight loss and temperature rise, reduced lung viral loads and shedding, and less lung damage.These data demonstrate the prophylactic and therapeutic efficacy of this new class of human monoclonal antibodies in a highly stringent and clinically relevant animal model of influenza and justify clinical development of this approach as intervention for both seasonal and pandemic influenza.

  12. Nonimmune binding of equine immunoglobulin by the causative organism of contagious equine metritis, Taylorella equigenitalis.

    Science.gov (United States)

    Widders, P R; Stokes, C R; Newby, T J; Bourne, F J

    1985-05-01

    This study identifies nonimmune binding of equine immunoglobulin by the causative organism of contagious equine metritis. Immunoglobulin binding to the bacterium was strongest for immunoglobulin G (IgG) and less for IgM; IgA was not bound. Binding of equine IgG was inhibited by human IgG, but not by IgG of domestic animals. Immunoglobulin binding by the bacterium appeared to be directed towards an epitope in the hinge region of the immunoglobulin molecule.

  13. High prevalence of immunoglobulin A deficiency in patients with type 1 diabetes mellitus detected by ELISA

    OpenAIRE

    Loraine Farias Landgraf; Nelson Augusto Rosário; Juliana Ferreira de Moura; Katherine Andrew Wells; Bonald Cavalcanti Figueiredo

    2008-01-01

    Objective: To measure serum levels of immunoglobulin A byimmunoenzymatic assay (ELISA) in type 1 diabetes mellitus (DM-1)patients and to verify the prevalence of immunoglobulin A deficiency(IgAD) in diabetic patients. Methods: The serum immunoglobulin Alevel was determined in 149 DM-1 patients by three methods. IgADwas defined as serum immunoglobulin A level lower than 5 mg/dl.If serum immunoglobulin A level was undetectable by turbidimetry,radial immunodiffusion was performed in low plate co...

  14. Cerebrospinal fluid aquaporin-4-immunoglobulin G disrupts blood brain barrier

    DEFF Research Database (Denmark)

    Asgari, Nasrin; Berg, Carsten Tue; Mørch, Marlene Thorsen

    2015-01-01

    was evaluated. A distinct distribution pattern of aquaporin-4-immunoglobulin G deposition was observed in the subarachnoid and subpial spaces where vessels penetrate the brain parenchyma, via a paravascular route with intraparenchymal perivascular deposition. Perivascular astrocyte-destructive lesions were...... associated with blood-borne horseradish peroxidase leakage indicating blood-brain barrier breakdown. The cerebrospinal fluid aquaporin-4-immunoglobulin G therefore distributes widely in brain to initiate astrocytopathy and blood-brain barrier breakdown....

  15. Efficacy and tolerability of 16% subcutaneous immunoglobulin compared with 20% subcutaneous immunoglobulin in primary antibody deficiency.

    Science.gov (United States)

    Niebur, H B; Duff, C M; Shear, G F; Nguyen, D; Alberdi, T K; Dorsey, M J; Sleasman, J W

    2015-09-01

    Multiple subcutaneous immunoglobulin (SCIG) products are available to treat primary antibody deficiency (PAD). The efficacy and tolerability of 16% SCIG (Vivaglobin(®) ) was compared with 20% SCIG (Hizentra(®) ) in PAD subjects. The study was a prospective, single-centre, open-label study of PAD subjects transitioning Vivaglobin to equivalent Hizentra doses, rounded to the nearest vial size. Comparisons included immunoglobulin (Ig)G levels; tetanus, varicella and Streptococcus pneumoniae titres; adverse events (AEs), annual infection rate and quality of life during 8 weeks of Vivaglobin and 24 weeks of Hizentra. Thirty-two subjects (aged 2-75 years) participated. Rounding to the nearest Hizentra vial size resulted in a 12·8% (± 2·9%) increase in SCIG dose. Median immunoglobulin (Ig)G level following 8 weeks of Vivaglobin was similar to 24 weeks of Hizentra (1050 versus 1035 mg/dl, respectively; P = 0·77). Both products had similar protective titres to tetanus, varicella and serotypes of S. pneumoniae, which were variable but well above protective levels. After 12 weeks of Hizentra, subjects reported fewer local site reactions compared with Vivaglobin. Switching products resulted in increased systemic AEs in some subjects but, overall, not significantly higher than during Vivaglobin treatment. Average infusion time decreased from 104·7 min (3·3 sites) with Vivaglobin to 70·7 min (2·2 sites) with Hizentra (P = 0·0005). Acute serious bacterial infections were similar. Treatment satisfaction was superior with Hizentra. Hizentra and Vivaglobin have similar pharmacokinetics and efficacy. Although transition to a different SCIG product initially increased AEs, Hizentra is well tolerated and can be infused more rapidly and with fewer sites compared to Vivaglobin. © 2015 British Society for Immunology.

  16. Immunoglobulin Expression in Non-Lymphoid Lineage and Neoplastic Cells

    Science.gov (United States)

    Chen, Zhengshan; Qiu, Xiaoyan; Gu, Jiang

    2009-01-01

    It has traditionally been believed that the production of immunoglobulin (Ig) molecules is restricted to B lineage cells. However, immunoglobulin genes and proteins have been recently found in a variety of types of cancer cells, as well as some proliferating epithelial cells and neurons. The immunoglobulin molecules expressed by these cells consist predominantly of IgG, IgM, and IgA, and the light chains expressed are mainly kappa chains. Recombination activating genes 1 and 2, which are required for V(D)J recombination, are also expressed in these cells. Knowledge about the function of these non-lymphoid cell-derived immunoglobulins is limited. Preliminary data suggests that Ig secreted by epithelial cancer cells has some unidentified capacity to promote the growth and survival of tumor cells. As immunoglobulins are known to have a wide spectrum of important functions, the discovery of non-lymphoid cells and cancers that produce immunoglobulin calls for in-depth investigation of the functional and pathological significance of this previously unrecognized phenomenon. PMID:19246641

  17. Immunoglobulin expression in non-lymphoid lineage and neoplastic cells.

    Science.gov (United States)

    Chen, Zhengshan; Qiu, Xiaoyan; Gu, Jiang

    2009-04-01

    It has traditionally been believed that the production of immunoglobulin (Ig) molecules is restricted to B lineage cells. However, immunoglobulin genes and proteins have been recently found in a variety of types of cancer cells, as well as some proliferating epithelial cells and neurons. The immunoglobulin molecules expressed by these cells consist predominantly of IgG, IgM, and IgA, and the light chains expressed are mainly kappa chains. Recombination activating genes 1 and 2, which are required for V(D)J recombination, are also expressed in these cells. Knowledge about the function of these non-lymphoid cell-derived immunoglobulins is limited. Preliminary data suggests that Ig secreted by epithelial cancer cells has some unidentified capacity to promote the growth and survival of tumor cells. As immunoglobulins are known to have a wide spectrum of important functions, the discovery of non-lymphoid cells and cancers that produce immunoglobulin calls for in-depth investigation of the functional and pathological significance of this previously unrecognized phenomenon.

  18. Cytomegalovirus Immunoglobulin After Thoracic Transplantation: An Overview.

    Science.gov (United States)

    Grossi, Paolo; Mohacsi, Paul; Szabolcs, Zoltán; Potena, Luciano

    2016-03-01

    Cytomegalovirus (CMV) is a highly complex pathogen which, despite modern prophylactic regimens, continues to affect a high proportion of thoracic organ transplant recipients. The symptomatic manifestations of CMV infection are compounded by adverse indirect effects induced by the multiple immunomodulatory actions of CMV. These include a higher risk of acute rejection, cardiac allograft vasculopathy after heart transplantation, and potentially bronchiolitis obliterans syndrome in lung transplant recipients, with a greater propensity for opportunistic secondary infections. Prophylaxis for CMV using antiviral agents (typically oral valganciclovir or intravenous ganciclovir) is now almost universal, at least in high-risk transplants (D+/R-). Even with extended prophylactic regimens, however, challenges remain. The CMV events can still occur despite antiviral prophylaxis, including late-onset infection or recurrent disease, and patients with ganciclovir-resistant CMV infection or who are intolerant to antiviral therapy require alternative strategies. The CMV immunoglobulin (CMVIG) and antiviral agents have complementary modes of action. High-titer CMVIG preparations provide passive CMV-specific immunity but also exert complex immunomodulatory properties which augment the antiviral effect of antiviral agents and offer the potential to suppress the indirect effects of CMV infection. This supplement discusses the available data concerning the immunological and clinical effects of CMVIG after heart or lung transplantation.

  19. Restricted, canonical, stereotyped and convergent immunoglobulin responses.

    Science.gov (United States)

    Henry Dunand, Carole J; Wilson, Patrick C

    2015-09-05

    It is becoming evident that B-cell responses to particular epitopes or in particular contexts can be highly convergent at the molecular level. That is, depending on the epitope targeted, persons of diverse genetic backgrounds and immunological histories can use highly similar, stereotyped B-cell receptors (BCRs) for a particular response. In some cases, multiple people with immunity to a particular epitope or with a type of B-cell neoplasia will elicit antibodies encoded by essentially identical immunoglobulin gene rearrangements. In other cases, particular VH genes encode antibodies important for immunity against pathogens such as influenza and HIV. It appears that the conserved antibody structures driving these stereotyped responses are highly limited and selected. There are interesting and important convergences in the types of stereotyped BCRs induced in conditions of immunity and B-cell-related pathology such as cancer and autoimmunity. By characterizing and understanding stereotyped B-cell responses, novel approaches to B-cell immunity and in understanding the underlying causes of B-cell pathology may be discovered. In this paper, we will review stereotyped BCR responses in various contexts of B-cell immunity and pathology. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  20. Killer immunoglobulin receptor genes in spondyloarthritis.

    Science.gov (United States)

    Kuijpers, Taco W; Vendelbosch, Sanne; Berg, Merlijn van den; Baeten, Dominique L P

    2016-07-01

    We focus on the role of killer immunoglobulin receptor (KIR) interactions with the human leukocyte antigens (HLA)-B27 ligand and the potential contribution of KIR-expressing natural killer and T cells in spondyloarthritis, more specifically in ankylosing spondylitis (AS). In AS strong epidemiological evidence of significant genetic associations with the major histocompatibility complex was convincingly identified. HLA-B27-positive first-degree relatives of AS cases are 5-16 times more likely to develop disease than HLA-B27-positive carriers in the general community. The GWAS era has enabled rapid progress in identifying non-major histocompatibility complex associations of AS. These findings show a number of important pathways in AS pathogenesis, including the IL-23-IL-17 pathway, aminopeptidases, peptide presentation, and KIR-HLA-B27 interactions. Studies using genetic markers, including KIRs may be used for a risk assessment about whom may benefit most from the various treatment protocols in spondyloarthritis, now that alternative therapeutic options have become feasible.

  1. Plasma cytokines in acute stroke

    DEFF Research Database (Denmark)

    Christensen, Hanne Krarup; Boysen, Gudrun; Christensen, Erik

    2011-01-01

    GOALS: The aim of this study was to test the relations between plasma cytokines and the clinical characteristics, course, and risk factors in acute stroke. PATIENTS AND METHODS: The analysis was based on 179 patients with acute stroke included within 24 hours of stroke onset. On inclusion and 3...... months later plasma levels of interleukin 1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), interleukin-1 receptor antagonist (IL-1RA), interleukin 6 (IL-6), interleukin 10 (IL-10), soluble tumor necrosis factor receptor 1 (sTNF-R1), and soluble tumor necrosis factor receptor 2 (sTNF-R2) were...

  2. Influenza H5 hemagglutinin DNA primes the antibody response elicited by the live attenuated influenza A/Vietnam/1203/2004 vaccine in ferrets.

    Directory of Open Access Journals (Sweden)

    Amorsolo L Suguitan

    Full Text Available Priming immunization plays a key role in protecting individuals or populations to influenza viruses that are novel to humans. To identify the most promising vaccine priming strategy, we have evaluated different prime-boost regimens using inactivated, DNA and live attenuated vaccines in ferrets. Live attenuated influenza A/Vietnam/1203/2004 (H5N1 candidate vaccine (LAIV, VN04 ca primed ferrets efficiently while inactivated H5N1 vaccine could not prime the immune response in seronegative ferrets unless an adjuvant was used. However, the H5 HA DNA vaccine alone was as successful as an adjuvanted inactivated VN04 vaccine in priming the immune response to VN04 ca virus. The serum antibody titers of ferrets primed with H5 HA DNA followed by intranasal vaccination of VN04 ca virus were comparable to that induced by two doses of VN04 ca virus. Both LAIV-LAIV and DNA-LAIV vaccine regimens could induce antibody responses that cross-neutralized antigenically distinct H5N1 virus isolates including A/HongKong/213/2003 (HK03 and prevented nasal infection of HK03 vaccine virus. Thus, H5 HA DNA vaccination may offer an alternative option for pandemic preparedness.

  3. A live attenuated cold-adapted influenza A H7N3 virus vaccine provides protection against homologous and heterologous H7 viruses in mice and ferrets

    International Nuclear Information System (INIS)

    Joseph, Tomy; McAuliffe, Josephine; Lu, Bin; Vogel, Leatrice; Swayne, David; Jin, Hong; Kemble, George; Subbarao, Kanta

    2008-01-01

    The appearance of human infections caused by avian influenza A H7 subtype viruses underscores their pandemic potential and the need to develop vaccines to protect humans from viruses of this subtype. A live attenuated H7N3 virus vaccine was generated by reverse genetics using the HA and NA genes of a low pathogenicity A/chicken/BC/CN-6/04 (H7N3) virus and the six internal protein genes of the cold-adapted A/Ann Arbor/6/60 ca (H2N2) virus. The reassortant H7N3 BC 04 ca vaccine virus was temperature sensitive and showed attenuation in mice and ferrets. Intranasal immunization with one dose of the vaccine protected mice and ferrets when challenged with homologous and heterologous H7 viruses. The reassortant H7N3 BC 04 ca vaccine virus showed comparable levels of attenuation, immunogenicity and efficacy in mice and ferret models. The safety, immunogenicity, and efficacy of this vaccine in mice and ferrets support the evaluation of this vaccine in clinical trials

  4. Plasmid DNA-based vaccines protect mice and ferrets against lethal challenge with A/Vietnam/1203/04 (H5N1) influenza virus.

    Science.gov (United States)

    Lalor, Peggy A; Webby, Richard J; Morrow, Jane; Rusalov, Denis; Kaslow, David C; Rolland, Alain; Smith, Larry R

    2008-06-15

    Plasmid DNA (pDNA) vaccines represent an alternative to conventional inactivated influenza vaccines that are likely to experience supply constraints during a pandemic. Several Vaxfectin-formulated pDNA vaccines were tested in mice and ferrets for efficacy against a lethal challenge with the highly pathogenic A/Vietnam/1203/04 (H5N1) influenza virus strain; the vaccines encoded influenza A virus hemagglutinin (HA), and/or nucleoprotein (NP), and M2 protein. Complete protection from death and disease was achieved in mice and ferrets with 2 doses of a Vaxfectin-formulated vaccine containing H5 HA, NP, and M2 plasmids and in ferrets with only 1 dose. A Vaxfectin-formulated vaccine containing NP and M2 pDNA provided significant protection against death in mice and provided some benefit in ferrets (i.e., 17% survival, delayed time to illness and death, and significant reduction in viral load compared with that in negative control animals). These experiments support the clinical testing of pDNA vaccine candidates that may ultimately increase global vaccine supply options during pandemics.

  5. Infection with human H1N1 influenza virus affects the expression of sialic acids of metaplastic mucous cells in the ferret airways

    DEFF Research Database (Denmark)

    Kirkeby, Svend; Martel, Cyril Jean-Marie; Aasted, Bent

    2009-01-01

    Glycans terminating in sialic acids serve as receptors for influenza viruses. In this study ferrets were infected with influenza virus A/New Caledonia/20/99, and the in situ localization of sialic acids linked a2-3 and a2-6 in the airways was investigated in infected and non-infected animals by u...

  6. Interval Between Infections and Viral Hierarchy Are Determinants of Viral Interference Following Influenza Virus Infection in a Ferret Model

    Science.gov (United States)

    Laurie, Karen L.; Guarnaccia, Teagan A.; Carolan, Louise A.; Yan, Ada W. C.; Aban, Malet; Petrie, Stephen; Cao, Pengxing; Heffernan, Jane M.; McVernon, Jodie; Mosse, Jennifer; Kelso, Anne; McCaw, James M.; Barr, Ian G.

    2015-01-01

    Background. Epidemiological studies suggest that, following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other influenza viruses. This viral interference appears to be independent of any antigenic similarities between the viruses. We used the ferret model of human influenza to systematically investigate viral interference. Methods. Ferrets were first infected then challenged 1–14 days later with pairs of influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B viruses circulating in 2009 and 2010. Results. Viral interference was observed when the interval between initiation of primary infection and subsequent challenge was infections. Ongoing shedding from the primary virus infection was associated with viral interference after the secondary challenge. Conclusions. The interval between infections and the sequential combination of viruses were important determinants of viral interference. The influenza viruses in this study appear to have an ordered hierarchy according to their ability to block or delay infection, which may contribute to the dominance of different viruses often seen in an influenza season. PMID:25943206

  7. Cold exposure down-regulates immune response pathways in ferret aortic perivascular adipose tissue

    NARCIS (Netherlands)

    Reynés, Bàrbara; Schothorst, van Evert M.; García-Ruiz, Estefanía; Keijer, Jaap; Palou, Andreu; Oliver, Paula

    2017-01-01

    Perivascular adipose tissue (PVAT) surrounds blood vessels and releases paracrine factors, such as cytokines, which regulate local inflammation. The inflammatory state of PVAT has an important role in vascular disease; a pro-inflammatory state has been related with atherosclerosis development,

  8. Cytokines and cytokine networks target neurons to modulate long-term potentiation.

    Science.gov (United States)

    Prieto, G Aleph; Cotman, Carl W

    2017-04-01

    Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Altered sexual partner preference in male ferrets given excitotoxic lesions of the preoptic area/anterior hypothalamus.

    Science.gov (United States)

    Paredes, R G; Baum, M J

    1995-10-01

    Numerous experiments suggest that perinatal exposure of male vertebrates to testosterone (T), or its estrogenic metabolites, masculinizes aspects of coital function, including males' characteristic preference to seek out and mate with a female as opposed to another male conspecific. Other research has shown that this perinatal action of sex steroids also masculinizes aspects of neuronal morphology in the medial preoptic area/anterior hypothalamus (mPOA/AH). We asked whether neurons of the mPOA/AH contribute to males' preference to mate with a female. The ferret is an ideal species in which to ask this question. When tested in a T-maze after gonadectomy and treatment with estradiol benzoate (EB), female ferrets prefer to approach and receive neck grips from a stimulus male whereas males prefer to approach and neck grip an estrous female. In the minority of trials when EB-treated males approach a stimulus male, they occasionally receive a neck grip to which they display receptive postures as opposed to agonistic behaviors. In Experiment 1 castrated, EB-treated male ferrets which received bilateral infusions of the NMDA excitotoxin, quinolinic acid aimed at the dorsomedial POA/AH, preferred to approach a stimulus male significantly more often than groups of control males which either received a sham lesion, received a unilateral mPOA/AH lesion or in which bilateral infusions of quinolinic aci produced no histologically detectible excitotoxic damage to the mPOA/AH. Males with bilateral mPOA/AH lesions also displayed neck gripping on a significantly lower percentage of trials than control males when they approached the stimulus female. Ovariectomized, EB-treated female ferrets with bilateral mPOA/AH lesions, like control females, preferred to approach and receive neck grips from a stimulus male. The males used in Experiment 1 had never experienced circulating levels of T characteristic of the breeding season. Therefore, in Experiment 2 prepubertally gonadectomized males

  10. Bovine Immunoglobulin/Protein Isolate Binds Pro-Inflammatory Bacterial Compounds and Prevents Immune Activation in an Intestinal Co-Culture Model

    Science.gov (United States)

    Detzel, Christopher J.; Horgan, Alan; Henderson, Abigail L.; Petschow, Bryon W.; Warner, Christopher D.; Maas, Kenneth J.; Weaver, Eric M.

    2015-01-01

    Intestinal barrier dysfunction is associated with chronic gastrointestinal tract inflammation and diseases such as IBD and IBS. Serum-derived bovine immunoglobulin/protein isolate (SBI) is a specially formulated protein preparation (>90%) for oral administration. The composition of SBI is greater than 60% immunoglobulin including contributions from IgG, IgA, and IgM. Immunoglobulin within the lumen of the gut has been recognized to have anti-inflammatory properties and is involved in maintaining gut homeostasis. The binding of common intestinal antigens (LPS and Lipid A) and the ligand Pam3CSK4, by IgG, IgA, and IgM in SBI was shown using a modified ELISA technique. Each of these antigens stimulated IL-8 and TNF-α cytokine production by THP-1 monocytes. Immune exclusion occurred as SBI (≤50 mg/mL) bound free antigen in a dose dependent manner that inhibited cytokine production by THP-1 monocytes in response to 10 ng/mL LPS or 200 ng/mL Lipid A. Conversely, Pam3CSK4 stimulation of THP-1 monocytes was unaffected by SBI/antigen binding. A co-culture model of the intestinal epithelium consisted of a C2BBe1 monolayer separating an apical compartment from a basal compartment containing THP-1 monocytes. The C2BBe1 monolayer was permeabilized with dimethyl palmitoyl ammonio propanesulfonate (PPS) to simulate a damaged epithelial barrier. Results indicate that Pam3CSK4 was able to translocate across the PPS-damaged C2BBe1 monolayer. However, binding of Pam3CSK4 by immunoglobulins in SBI prevented Pam3CSK4 translocation across the damaged C2BBe1 barrier. These results demonstrated steric exclusion of antigen by SBI which prevented apical to basal translocation of antigen due to changes in the physical properties of Pam3CSK4, most likely as a result of immunoglobulin binding. This study demonstrates that immunoglobulins in SBI can reduce antigen-associated inflammation through immune and steric exclusion mechanisms and furthers the mechanistic understanding of how SBI

  11. Enhanced virulence of clade 2.3.2.1 highly pathogenic avian influenza A H5N1 viruses in ferrets.

    Science.gov (United States)

    Pearce, Melissa B; Pappas, Claudia; Gustin, Kortney M; Davis, C Todd; Pantin-Jackwood, Mary J; Swayne, David E; Maines, Taronna R; Belser, Jessica A; Tumpey, Terrence M

    2017-02-01

    Sporadic avian to human transmission of highly pathogenic avian influenza (HPAI) A(H5N1) viruses necessitates the analysis of currently circulating and evolving clades to assess their potential risk. Following the spread and sustained circulation of clade 2 viruses across multiple continents, numerous subclades and genotypes have been described. To better understand the pathogenesis associated with the continued diversification of clade 2A(H5N1) influenza viruses, we investigated the relative virulence of eleven human and poultry isolates collected from 2006 to 2013 by determining their ability to cause disease in the ferret model. Numerous clade 2 viruses, including a clade 2.2 avian isolate, a 2.2.2.1 human isolate, and two 2.2.1 human isolates, were found to be of low virulence in the ferret model, though lethality was detected following infection with one 2.2.1 human isolate. In contrast, three of six clade 2.3.2.1 avian isolates tested led to severe disease and death among infected ferrets. Clade 2.3.2.1b and 2.3.2.1c isolates, but not 2.3.2.1a isolates, were associated with ferret lethality. All A(H5N1) viruses replicated efficiently in the respiratory tract of ferrets regardless of their virulence and lethality. However, lethal isolates were characterized by systemic viral dissemination, including detection in the brain and enhanced histopathology in lung tissues. The finding of disparate virulence phenotypes between clade 2A(H5N1) viruses, notably differences between subclades of 2.3.2.1 viruses, suggests there are distinct molecular determinants present within the established subclades, the identification of which will assist in molecular-based surveillance and public health efforts against A(H5N1) viruses. Published by Elsevier Inc.

  12. Diffusion tensor imaging detects early cerebral cortex abnormalities in neuronal architecture induced by bilateral neonatal enucleation: An experimental model in the ferret

    Directory of Open Access Journals (Sweden)

    Andrew S Bock

    2010-10-01

    Full Text Available Diffusion tensor imaging (DTI is a technique that non-invasively provides quantitative measures of water translational diffusion, including fractional anisotropy (FA, that are sensitive to the shape and orientation of cellular elements, such as axons, dendrites and cell somas. For several neurodevelopmental disorders, histopathological investigations have identified abnormalities in the architecture of pyramidal neurons at early stages of cerebral cortex development. To assess the potential capability of DTI to detect neuromorphological abnormalities within the developing cerebral cortex, we compare changes in cortical FA with changes in neuronal architecture and connectivity induced by bilateral enucleation at postnatal day 7 (BEP7 in ferrets. We show here that the visual callosal pattern in BEP7 ferrets is more irregular and occupies a significantly greater cortical area compared to controls at adulthood. To determine whether development of the cerebral cortex is altered in BEP7 ferrets in a manner detectable by DTI, cortical FA was compared in control and BEP7 animals on postnatal day 31. Visual cortex, but not rostrally-adjacent non-visual cortex, exhibits higher FA than control animals, consistent with BEP7 animals possessing axonal and dendritic arbors of reduced complexity than age-matched controls. Subsequent to DTI, Golgi staining and analysis methods were used to identify regions, restricted to visual areas, in which the orientation distribution of neuronal processes is significantly more concentrated than in control ferrets. Together, these findings suggest that DTI can be of utility for detecting abnormalities associated with neurodevelopmental disorders at early stages of cerebral cortical development, and that the neonatally-enucleated ferret is a useful animal model system for systematically assessing the potential of this new diagnostic strategy.

  13. Bioanalytical Chemistry of Cytokines-A Review

    Science.gov (United States)

    Stenken, Julie A.; Poschenrieder, Andreas J.

    2014-01-01

    Cytokines are bioactive proteins produced by many different cells of the immune system. Due to their role in different inflammatory disease states and maintaining homeostasis, there is enormous clinical interest in the quantitation of cytokines. The typical standard methods for quantitation of cytokines are immunoassay-based techniques including enzyme-linked immusorbent assays (ELISA) and bead-based immunoassays read by either standard or modified flow cytometers. A review of recent developments in analytical methods for measurements of cytokine proteins is provided. This review briefly covers cytokine biology and the analysis challenges associated with measurement of these biomarker proteins for understanding both health and disease. New techniques applied to immunoassay-based assays are presented along with the uses of aptamers, electrochemistry, mass spectrometry, optical resonator-based methods. Methods used for elucidating the release of cytokines from single cells as well as in vivo collection methods are described. PMID:25467452

  14. Immunoglobulin E and systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Atta A.M.

    2004-01-01

    Full Text Available Systemic lupus erythematosus (SLE is an autoimmune disease characterized by intense polyclonal production of autoantibodies and circulating immune complexes. Some reports have associated SLE with a Th2 immune response and allergy. In the present study 21 female patients with SLE were investigated for total IgE and IgE antibodies to dust house aeroallergens by an automated enzyme-linked fluorescent assay, and were also evaluated for antinuclear IgE autoantibodies by a modified indirect immunofluorescence test using HEp-2 cells as antigen substrate. Additionally, immunocapture ELISA was used to investigate serum anti-IgE IgG autoantibodies. Serum IgE above 150 IU/ml, ranging from 152 to 609 IU/ml (median = 394 IU IgE/ml, was observed in 7 of 21 SLE patients (33%, 5 of them presenting proteinuria, urinary cellular casts and augmented production of anti-dsDNA antibodies. While only 2 of 21 SLE patients (9.5% were positive for IgE antibodies to aeroallergens, all 10 patients with respiratory allergy (100% from the atopic control group (3 males and 7 females, had these immunoglobulins. SLE patients and healthy controls presented similar anti-IgE IgG autoantibody titers (X = 0.37 ± 0.20 and 0.34 ± 0.18, respectively, differing from atopic controls (0.94 ± 0.26. Antinuclear IgE autoantibodies were detected in 17 of 21 (81% sera from SLE patients, predominating the fine speckled pattern of fluorescence, that was also observed in IgG-ANA. Concluding, SLE patients can present increased IgE levels and antinuclear IgE autoantibodies without specific clinical signs of allergy or production of antiallergen IgE antibodies, excluding a possible association between SLE and allergy.

  15. Immunoglobulin heavy chains in medaka (Oryzias latipes

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    Gambón-Deza Francisco

    2011-06-01

    Full Text Available Abstract Background Bony fish present an immunological system, which evolved independently from those of animals that migrated to land 400 million years ago. The publication of whole genome sequences and the availability of several cDNA libraries for medaka (Oryzias latipes permitted us to perform a thorough analysis of immunoglobulin heavy chains present in this teleost. Results We identified IgM and IgD coding ESTs, mainly in spleen, kidney and gills using published cDNA libraries but we did not find any sequence that coded for IgT or other heavy chain isotypes described in fish. The IgM - ESTs corresponded with the secreted and membrane forms and surprisingly, the latter form only presented two constant heavy chain domains. This is the first time that this short form of membrane IgM is described in a teleost. It is different from that identified in Notothenioid teleost because it does not present the typical splicing pattern of membrane IgM. The identified IgD-ESTs only present membrane transcripts, with Cμ1 and five Cδ exons. Furthermore, there are ESTs with sequences that do not have any VH which disrupt open reading frames. A scan of the medaka genome using transcripts and genomic short reads resulted in five zones within a region on chromosome 8 with Cμ and Cδ exons. Some of these exons do not form part of antibodies and were at times interspersed, suggesting a recombination process between zones. An analysis of the ESTs confirmed that no antibodies are expressed from zone 3. Conclusions Our results suggest that the IGH locus duplication is very common among teleosts, wherein the existence of a recombination process explains the sequence homology between them.

  16. CYTOKINE DISBALANCE AT HERPESVIRUS MYOCARDITIS

    Directory of Open Access Journals (Sweden)

    Peremot S. D

    2016-12-01

    Full Text Available Viral myocarditis is a heterogeneous group of diseases not only by etiologic factors, which belong to different families of Vira kingdom, but is also characterized by a unique mechanism of inflammatory process and cytokine levels specific for each of them. According to numerous researches in сardio-immunology, at herpesvirus infection of the cardiovascular system occur both systemic and localized violations of the immune response. Unfortunately, the accessible literature did not provide the data analysis of complex cardio-immunological research that would take into account the features of herpesvirus myocarditis clinical course. This grounds relevance of immunodiagnosis directed on the exposure of dysimmunities by study of indices of general and local immunity with the estimation of the immune status in patients depending on the stage of exasperation or relapse of chronic herpetic infection in the complex of diagnostic tests. The purpose of our research was to determine features of the state of the immune system with the complex analysis of cytokine profile data, immune and interferon statuses in subacute and chronic forms of herpesvirus myocarditis. Materials and methods. 87 myocarditis patients who were receiving inpatient treatment in medical establishments of Kharkiv were examined. The average age was (M ± m 36 ± 3,46 years old. The diagnosis of myocarditis was established according to the order № 436 by the Ministry of Healthcare of Ukraine from 03.07.2006 of clinical findings protocol. In accordance with the term of myocarditis clinical course, the patients were divided in two sub-groups: 44 patients with subacute (from 2 to 6 months, and 43 patients with chronic (over 6 months clinical course of viral myocarditis. The control group correlated with patients of basic group by age and gender and consisted of 40 practically healthy persons without implications of cardial pathology. Definition of cytokine concentration: IL-2, IL-4, IL-6

  17. High levels of immunoglobulin E and a continuous increase in immunoglobulin G and immunoglobulin M by age in children with newly diagnosed type 1 diabetes

    DEFF Research Database (Denmark)

    Svensson, Jannet; Eising, Stefanie; Mortensen, Henrik Bindesbøl

    2012-01-01

    The incidence of type 1 diabetes (T1D) is increasing, either because of environmental factors accelerating onset of the disease or because of inducement of autoimmune diabetes in children who previously were at lower risk. High levels of immunoglobulin (Ig), specifically, IgM and IgA, and a low...

  18. Visual Stimulus Speed Does Not Influence the Rapid Emergence of Direction Selectivity in Ferret Visual Cortex.

    Science.gov (United States)

    Ritter, Neil J; Anderson, Nora M; Van Hooser, Stephen D

    2017-02-08

    Sensory experience is necessary for the development of some receptive field properties of neurons in primary sensory cortical areas. However, it remains unclear whether the parameters of an individual animal's experience play an instructive role and influence the tuning parameters of cortical sensory neurons as selectivity emerges, or rather whether experience merely permits the completion of processes that are fully seeded at the onset of experience. Here we have examined whether the speed of visual stimuli that are presented to visually naive ferrets can influence the parameters of speed tuning and direction selectivity in cortical neurons. Visual experience is necessary for the development of direction selectivity in carnivores. If, during development, cortical neurons had the flexibility to choose from among different inputs with a range of spatial positions and temporal delays, then correlation-based plasticity mechanisms could instruct the precise spatiotemporal selectivity that underlies speed tuning and direction selectivity, and the parameters of an individual animal's experience would influence the tuning that emerges. Alternatively, the tuning parameters of these neurons may already be established at the onset of visual experience, and experience may merely permit the expression of this tuning. We found that providing different groups of animals with either slow (12.5 deg/s) or fast (50 deg/s) visual stimuli resulted in emergence of direction selectivity, but that speed tuning and direction selectivity were similar in the two groups. These results are more consistent with a permissive role for experience in the development of direction selectivity. SIGNIFICANCE STATEMENT The proper development of brain circuits and neural response properties depends on both nature (factors independent of experience) and nurture (factors dependent on experience). In this study, we examined whether the quality of visual experience of an individual animal influences the

  19. Initial pen and field assessment of baits to use in oral rabies vaccination of Formosan ferret-badgers in response to the re-emergence of rabies in Taiwan.

    Directory of Open Access Journals (Sweden)

    Ryan M Wallace

    Full Text Available Taiwan had been considered rabies free since 1961, until a newly established wildlife disease surveillance program identified rabies virus transmission within the Formosan ferret-badger (Melogale moschata subaurantiaca in 2013. Ferret-badgers occur throughout southern China and Southeast Asia, but their ecological niche is not well described.As an initial feasibility assessment for potential rabies control measures, field camera trapping and pen assessment of 6 oral rabies vaccine (ORV baits were conducted in Taiwan in 2013. 46 camera nights were recorded; 6 Formosan ferret-badgers and 14 non-target mammals were sighted. No baits were consumed by ferret-badgers and 8 were consumed by non-target mammals. Penned ferret-badgers ingested 5 of the 18 offered baits. When pen and field trials were combined, and analyzed for palatability, ferret-badgers consumed 1 of 9 marshmallow baits (11.1%, 1 of 21 fishmeal baits (4.8%, 0 of 3 liver baits, and 3 of 3 fruit-flavored baits. It took an average of 261 minutes before ferret-badgers made oral contact with the non-fruit flavored baits, and 34 minutes for first contact with the fruit-based bait. Overall, ferret-badgers sought out the fruit baits 8 times faster, spent a greater proportion of time eating fruit baits, and were 7.5 times more likely to have ruptured the vaccine container of the fruit-based bait.Ferret-badgers are now recognized as rabies reservoir species in China and Taiwan, through two independent 'dog to ferret-badger' host-shift events. Species of ferret-badgers can be found throughout Indochina, where they may be an unrecognized rabies reservoir. Findings from this initial study underscore the need for further captive and field investigations of fruit-based attractants or baits developed for small meso-carnivores. Non-target mammals' competition for baits, ants, bait design, and dense tropical landscape represent potential challenges to effective ORV programs that will need to be

  20. Initial pen and field assessment of baits to use in oral rabies vaccination of Formosan ferret-badgers in response to the re-emergence of rabies in Taiwan.

    Science.gov (United States)

    Wallace, Ryan M; Lai, Yuching; Doty, Jeffrey B; Chen, Chen-Chih; Vora, Neil M; Blanton, Jesse D; Chang, Susan S; Cleaton, Julie M; Pei, Kurtis J C

    2018-01-01

    Taiwan had been considered rabies free since 1961, until a newly established wildlife disease surveillance program identified rabies virus transmission within the Formosan ferret-badger (Melogale moschata subaurantiaca) in 2013. Ferret-badgers occur throughout southern China and Southeast Asia, but their ecological niche is not well described. As an initial feasibility assessment for potential rabies control measures, field camera trapping and pen assessment of 6 oral rabies vaccine (ORV) baits were conducted in Taiwan in 2013. 46 camera nights were recorded; 6 Formosan ferret-badgers and 14 non-target mammals were sighted. No baits were consumed by ferret-badgers and 8 were consumed by non-target mammals. Penned ferret-badgers ingested 5 of the 18 offered baits. When pen and field trials were combined, and analyzed for palatability, ferret-badgers consumed 1 of 9 marshmallow baits (11.1%), 1 of 21 fishmeal baits (4.8%), 0 of 3 liver baits, and 3 of 3 fruit-flavored baits. It took an average of 261 minutes before ferret-badgers made oral contact with the non-fruit flavored baits, and 34 minutes for first contact with the fruit-based bait. Overall, ferret-badgers sought out the fruit baits 8 times faster, spent a greater proportion of time eating fruit baits, and were 7.5 times more likely to have ruptured the vaccine container of the fruit-based bait. Ferret-badgers are now recognized as rabies reservoir species in China and Taiwan, through two independent 'dog to ferret-badger' host-shift events. Species of ferret-badgers can be found throughout Indochina, where they may be an unrecognized rabies reservoir. Findings from this initial study underscore the need for further captive and field investigations of fruit-based attractants or baits developed for small meso-carnivores. Non-target mammals' competition for baits, ants, bait design, and dense tropical landscape represent potential challenges to effective ORV programs that will need to be considered in future

  1. Serum immunoglobulins in head and neck cancer: effect of radiotherapy

    International Nuclear Information System (INIS)

    Kohli, G.S.; Yadav, S.P.S.; Chowdhry, D.; Mehta, H.C.

    1987-01-01

    Twenty-five patients with head and neck cancer and 25 age-matched normal controls were investigated for serum, immunoglobulin levels (IgA, IgG and IgM). The levels of all the three immunoglobulins in the patients were significantly higher than controls, the rise in IgA being more than that of IgG or IgM. The ratios of IgA/IgG and IgA/IgM were also higher than normal. The immunoglobulin levels showed a progressive rise with the advance in stage of the tumour. A fall in the immunoglobulin levels, as well as in the ratios of IgA/IgG and IgA/IgM, was noted following radiotherapy though the levels were still higher than controls. The range of increase in immunoglobulins appears to be a satisfactory prognostic tool, and a fall after radiotherapy appears to be related to the effectiveness of treatment. (author). 3 tables, 11 refs

  2. Uninvolved immunoglobulins predicting hematological response in newly diagnosed AL amyloidosis.

    Science.gov (United States)

    Muchtar, Eli; Magen, Hila; Itchaki, Gilad; Cohen, Amos; Rosenfeld, Ra'ama; Shochat, Tzippy; Kornowski, Ran; Iakobishvili, Zaza; Raanani, Pia

    2016-02-01

    Immunoparesis serves as a marker for elevated risk for progression in plasma cell proliferative disorders. However, the impact of immunoparesis in AL amyloidosis has not been addressed. Immunoparesis was defined qualitatively as any decrease below the low reference levels of the uninvolved immunoglobulins and quantitatively, as the relative difference between the uninvolved immunoglobulins and the lower reference values. Forty-one newly diagnosed AL amyloidosis patients were included. Sixty-six percent of patients had a suppression of the uninvolved immunoglobulins. The median relative difference of the uninvolved immunoglobulins was 18% above the low reference levels [range (-71%)-210%]. Ninety percent of the patients were treated with novel agents-based regimens, mostly bortezomib-containing regimens. Nineteen percent of the patients did not attain response to first line treatment. Patients with relative difference of uninvolved immunoglobulins below -25% of the low reference levels were less likely to respond to first line treatment compared to patients with a relative difference of -25% and above [odds ratio for no response vs. partial response and better 30 [(95% CI 4.1-222.2), P=0.0004]. Patients who failed first line treatment were successfully salvaged with lenalidomide-based treatment. Immunoparesis, if assessed quantitatively, may serve as a predictor of response in AL amyloidosis patients treated with bortezomib-containing regimens. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Antigen presentation profiling reveals recognition of lymphoma immunoglobulin neoantigens.

    Science.gov (United States)

    Khodadoust, Michael S; Olsson, Niclas; Wagar, Lisa E; Haabeth, Ole A W; Chen, Binbin; Swaminathan, Kavya; Rawson, Keith; Liu, Chih Long; Steiner, David; Lund, Peder; Rao, Samhita; Zhang, Lichao; Marceau, Caleb; Stehr, Henning; Newman, Aaron M; Czerwinski, Debra K; Carlton, Victoria E H; Moorhead, Martin; Faham, Malek; Kohrt, Holbrook E; Carette, Jan; Green, Michael R; Davis, Mark M; Levy, Ronald; Elias, Joshua E; Alizadeh, Ash A

    2017-03-30

    Cancer somatic mutations can generate neoantigens that distinguish malignant from normal cells. However, the personalized identification and validation of neoantigens remains a major challenge. Here we discover neoantigens in human mantle-cell lymphomas by using an integrated genomic and proteomic strategy that interrogates tumour antigen peptides presented by major histocompatibility complex (MHC) class I and class II molecules. We applied this approach to systematically characterize MHC ligands from 17 patients. Remarkably, all discovered neoantigenic peptides were exclusively derived from the lymphoma immunoglobulin heavy- or light-chain variable regions. Although we identified MHC presentation of private polymorphic germline alleles, no mutated peptides were recovered from non-immunoglobulin somatically mutated genes. Somatic mutations within the immunoglobulin variable region were almost exclusively presented by MHC class II. We isolated circulating CD4 + T cells specific for immunoglobulin-derived neoantigens and found these cells could mediate killing of autologous lymphoma cells. These results demonstrate that an integrative approach combining MHC isolation, peptide identification, and exome sequencing is an effective platform to uncover tumour neoantigens. Application of this strategy to human lymphoma implicates immunoglobulin neoantigens as targets for lymphoma immunotherapy.

  4. A live attenuated equine H3N8 influenza vaccine is highly immunogenic and efficacious in mice and ferrets.

    Science.gov (United States)

    Baz, Mariana; Paskel, Myeisha; Matsuoka, Yumiko; Zengel, James; Cheng, Xing; Treanor, John J; Jin, Hong; Subbarao, Kanta

    2015-02-01

    Equine influenza viruses (EIV) are responsible for rapidly spreading outbreaks of respiratory disease in horses. Although natural infections of humans with EIV have not been reported, experimental inoculation of humans with these viruses can lead to a productive infection and elicit a neutralizing antibody response. Moreover, EIV have crossed the species barrier to infect dogs, pigs, and camels and therefore may also pose a threat to humans. Based on serologic cross-reactivity of H3N8 EIV from different lineages and sublineages, A/equine/Georgia/1/1981 (eq/GA/81) was selected to produce a live attenuated candidate vaccine by reverse genetics with the hemagglutinin and neuraminidase genes of the eq/GA/81 wild-type (wt) virus and the six internal protein genes of the cold-adapted (ca) A/Ann Arbor/6/60 (H2N2) vaccine donor virus, which is the backbone of the licensed seasonal live attenuated influenza vaccine. In both mice and ferrets, intranasal administration of a single dose of the eq/GA/81 ca vaccine virus induced neutralizing antibodies and conferred complete protection from homologous wt virus challenge in the upper respiratory tract. One dose of the eq/GA/81 ca vaccine also induced neutralizing antibodies and conferred complete protection in mice and nearly complete protection in ferrets upon heterologous challenge with the H3N8 (eq/Newmarket/03) wt virus. These data support further evaluation of the eq/GA/81 ca vaccine in humans for use in the event of transmission of an equine H3N8 influenza virus to humans. Equine influenza viruses have crossed the species barrier to infect other mammals such as dogs, pigs, and camels and therefore may also pose a threat to humans. We believe that it is important to develop vaccines against equine influenza viruses in the event that an EIV evolves, adapts, and spreads in humans, causing disease. We generated a live attenuated H3N8 vaccine candidate and demonstrated that the vaccine was immunogenic and protected mice and

  5. Cross-protection against lethal H5N1 challenge in ferrets with an adjuvanted pandemic influenza vaccine.

    Directory of Open Access Journals (Sweden)

    Benoît Baras

    Full Text Available BACKGROUND: Unprecedented spread between birds and mammals of highly pathogenic avian influenza viruses (HPAI of the H5N1 subtype has resulted in hundreds of human infections with a high fatality rate. This has highlighted the urgent need for the development of H5N1 vaccines that can be produced rapidly and in sufficient quantities. Potential pandemic inactivated vaccines will ideally induce substantial intra-subtypic cross-protection in humans to warrant the option of use, either prior to or just after the start of a pandemic outbreak. In the present study, we evaluated a split H5N1 A/H5N1/Vietnam/1194/04, clade 1 candidate vaccine, adjuvanted with a proprietary oil-in- water emulsion based Adjuvant System proven to be well-tolerated and highly immunogenic in the human (Leroux-Roels et al. (2007 The Lancet 370:580-589, for its ability to induce intra-subtypic cross-protection against clade 2 H5N1/A/Indonesia/5/05 challenge in ferrets. METHODOLOGY AND PRINCIPAL FINDINGS: All ferrets in control groups receiving non-adjuvanted vaccine or adjuvant alone failed to develop specific or cross-reactive neutralizing antibodies and all died or had to be euthanized within four days of virus challenge. Two doses of adjuvanted split H5N1 vaccine containing >or=1.7 microg HA induced neutralizing antibodies in the majority of ferrets to both clade 1 (17/23 (74% responders and clade 2 viruses (14/23 (61% responders, and 96% (22/23 of vaccinees survived the lethal challenge. Furthermore lung virus loads and viral shedding in the upper respiratory tract were reduced in vaccinated animals relative to controls suggesting that vaccination might also confer a reduced risk of viral transmission. CONCLUSION: These protection data in a stringent challenge model in association with an excellent clinical profile highlight the potential of this adjuvanted H5N1 candidate vaccine as an effective tool in pandemic preparedness.

  6. Low pH gel intranasal sprays inactivate influenza viruses in vitro and protect ferrets against influenza infection

    Directory of Open Access Journals (Sweden)

    Lambkin-Williams Robert

    2007-05-01

    Full Text Available Abstract Background Developing strategies for controlling the severity of pandemic influenza is a global public health priority. In the event of a pandemic there may be a place for inexpensive, readily available, effective adjunctive therapies to support containment strategies such as prescription antivirals, vaccines, quarantine and restrictions on travel. Inactivation of virus in the intranasal environment is one possible approach. The work described here investigated the sensitivity of influenza viruses to low pH, and the activity of low pH nasal sprays on the course of an influenza infection in the ferret model. Methods Inactivation of influenza A and avian reassortment influenza was determined using in vitro solutions tests. Low pH nasal sprays were tested using the ferret model with an influenza A Sydney/5/97 challenge. Clinical measures were shed virus, weight loss and body temperature. Results The virus inactivation studies showed that influenza viruses are rapidly inactivated by contact with acid buffered solutions at pH 3.5. The titre of influenza A Sydney/5/97 [H3N2] was reduced by at least 3 log cycles with one minute contact with buffers based on simple acid mixtures such as L-pyroglutamic acid, succinic acid, citric acid and ascorbic acid. A pH 3.5 nasal gel composition containing pyroglutamic acid, succinic acid and zinc acetate reduced titres of influenza A Hong Kong/8/68 [H3N2] by 6 log cycles, and avian reassortment influenza A/Washington/897/80 X A Mallard/New York/6750/78 [H3N2] by 5 log cycles, with 1 min contact. Two ferret challenge studies, with influenza A Sydney/5/97, demonstrated a reduction in the severity of the disease with early application of low pH nasal sprays versus a saline control. In the first study there was decreased weight loss in the treatment groups. In the second study there were reductions in virus shedding and weight loss, most notably when a gelling agent was added to the low pH formulation

  7. Dermatology and Immunoglobulin Therapy: Who to Treat and How to Administer Immunoglobulins.

    Science.gov (United States)

    Navarro-Triviño, F J; Pérez-López, I; Ruíz-Villaverde, R

    2018-02-08

    Intravenous immunoglobulin (IVIG) replacement therapy has been used in immune deficiency diseases for more than 50 years. The indications for this treatment have evolved, however, and IVIG therapy is now used in various diseases in which the immune system plays a prominent role. IVIG therapy has carved out a niche in dermatology for the treatment of such conditions as dermatomyositis, autoimmune bullous diseases, and toxic epidermal necrolysis. Special attention has been paid to this therapy in recent years. New guidelines have been published and should be taken into consideration in dermatology. This review provides a practical guide to IVIG use in our specialty. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. [Sinonasal polyposis associated with a deficiency subclass immunoglobulin G: Place of substitution immunoglobulins].

    Science.gov (United States)

    Hoan, Nhung Tran Khai; Karmochkine, M; Laccourreye, O; Bonfils, P

    2014-01-01

    To study the effect of the introduction of a substitution by intravenous Immunoglobulins (Ig IV) at patients with immunoglobulins G (IgG) subclasses deficiency and nasal polyposis. Prospective study concerning five patients with IgG subclasses deficiency and nasal polyposis treated by Ig IV. Rhinologic, otologic and pulmonary symptoms, exacerbations of nasal polyposis, chronic otitis and asthma as well as the number of antibiotics and corticoids treatments were counted during the Ig IV substitution. To study the association between IgIV substitution and the number of exacerbations of nasal polyposis, chronic otitis, asthma and the number of antibiotics and corticoids treatments in patients with IgG subclasses deficiency and nasal polyposis. Five patients with a IgG subclass deficiency and nasal polyposis were substituted. The number of antibiotics and corticoids cures increased at one patient and remained stable at four others. The number of sinus, ear and lung infections as well as the global rhinologic score of symptoms and the endoscopic stage of the nasal polyposis remained stable. In the absence of efficiency of the treatment, this one was interrupted at the end of 6 months for patients n° 1 and n° 3, 24 months for patient n° 4 and 42 months for patient n° 5. The current study failed to highlight clinical improvement in patients wih IgG subclasses deficiency and nasal polyposis treated by Ig IV. A previous study had not allowed to find a link between IgG subclasses deficiency and severity of nasal polyposis, what seems to be confirmed by the absence of improvement brought during the substitution of this deficit in the current study.

  9. Non-immune immunoglobulins shield Schistosoma japonicum from host immunorecognition

    Science.gov (United States)

    Wu, Chuang; Hou, Nan; Piao, Xianyu; Liu, Shuai; Cai, Pengfei; Xiao, Yan; Chen, Qijun

    2015-01-01

    Schistosomiasis is a major human parasitic disease with a global impact. Schistosoma japonicum, the most difficult to control, can survive within host veins for decades. Mechanisms of immune evasion by the parasite, including antigenic variation and surface masking, have been implicated but not well defined. In this study, we defined the immunoglobulin-binding proteomes of S. japonicum using human IgG, IgM, and IgE as the molecular bait for affinity purification, followed by protein identification by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Several proteins situated at the tegument of S. japonicum were able to nonselectively bind to the Fc domain of host immunoglobulins, indicating a mechanism for the avoidance of host immune attachment and recognition. The profile of the immunoglobulin-binding proteomes provides further clues for immune evasion mechanisms adopted by S. japonicum. PMID:26299686

  10. Cytokine profile of cervical cancer cells

    NARCIS (Netherlands)

    Hazelbag, S.; Fleuren, G. J.; Baelde, J. J.; Schuuring, E.; Kenter, G. G.; Gorter, A.

    2001-01-01

    OBJECTIVE: In patients with cervical carcinoma, the presence of cytokines produced by T(H)2 cells, and the presence of an eosinophilic inflammatory infiltrate, has been associated with a less effective immune response and tumor progression. In the present study, we have investigated the cytokine

  11. Cytokine profile of cervical cancer cells

    NARCIS (Netherlands)

    Hazelbag, S; Fleuren, GJ; Baelde, JJ; Schuuring, E; Kenter, GG; Gorter, A

    2001-01-01

    Objective. In patients with cervical carcinoma, the presence of cytokines produced by T(H)2 cells, and the presence of an eosinophilic inflammatory infiltrate, has been associated with a less effective immune response and tumor progression. In the present study, we have investigated the cytokine

  12. Cytokines and organ failure in acute pancreatitis

    DEFF Research Database (Denmark)

    Malmstrøm, Marie Louise; Hansen, Mark Berner; Andersen, Anders Møller

    2012-01-01

    We aimed at synchronously examining the early time course of 4 proinflammatory cytokines as predictive factors for development of organ failure in patients with acute pancreatitis (AP).......We aimed at synchronously examining the early time course of 4 proinflammatory cytokines as predictive factors for development of organ failure in patients with acute pancreatitis (AP)....

  13. Cytokine gene expression of peripheral blood lymphocytes ...

    African Journals Online (AJOL)

    Lipopolysaccharide (LPS) is a predominant glycolipid in the outer membranes of gam-negative bacteria that stimulates monocytes, macrophages, and neutrophils to produce cytokines. The aim was to study the expression profile of TLRs and cytokines and determine the role of LPS in the peripheral blood lymphocytes.

  14. Clinical Applications of Intravenous Immunoglobulins in Child Neurology.

    Science.gov (United States)

    Gogou, Maria; Papadopoulou-Alataki, Efimia; Spilioti, Martha; Alataki, Sofia; Evangeliou, Athanasios

    2017-11-10

    While there are guidelines for the use of intravenous immunoglobulins in children with Guillain-Barre syndrome and myasthenia gravis based on high-level evidence studies, data are scarce for the majority of neurologic disorders in this age group. Neuronal antibodies are detected in children with seizures of autoimmune etiology. Intravenous immunoglobulins with their broad immunomodulatory mechanism of action could be ideally effective in different forms of immunedysregulated intractable epilepsies such as autoimmune epilepsy and autoimmune Rasmussen encephalitis. We conducted a systematic review of the literature for evidence of the use of intravenous immunoglobulins in a variety of neurologic diseases in childhood. A comprehensive literature search was conducted using Pubmed as the medical database source without date range. Prospective studies in pediatric groups including objective measures of clinical outcomes were systematically selected. A total of 11 prospective studies were identified in the literature demonstrating a favorable effect of this therapeutic option in children with drug-resistant epilepsy and in cases of encephalitis. No serious adverse effects were reported. No prospective studies about the use of intravenous immunoglobulins in children with demyelinating disorders or neurologic paraneoplasmatic syndromes were found. In this review, we summarize the recent advances in the field of intravenous immunoglobulins used in pediatric neurological diseases. Literature data supports a beneficial effect in this age group. Whilst awaiting the results of large scale studies, administration of intravenous immunoglobulins could be justified in refractory child epilepsy. Otherwise, its use should be guided by the individual needs of each child, depending on the underlying neurological disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Attenuation of Colitis by Serum-Derived Bovine Immunoglobulin/Protein Isolate in a Defined Microbiota Mouse Model.

    Science.gov (United States)

    Henderson, Abigail L; Brand, Meghan Wymore; Darling, Ross J; Maas, Kenneth J; Detzel, Christopher J; Hostetter, Jesse; Wannemuehler, Michael J; Weaver, Eric M

    2015-11-01

    The pathogenesis of inflammatory bowel disease (IBD) is complex and multifaceted including genetic predisposition, environmental components, microbial dysbiosis, and inappropriate immune activation to microbial components. Pathogenic bacterial provocateurs like adherent and invasive E. coli have been reported to increase susceptibility to Crohn's disease. Serum-derived bovine immunoglobulin/protein isolate (SBI) is comprised primarily of immunoglobulins (Igs) that bind to conserved microbial components and neutralize exotoxins. To demonstrate that oral administration of SBI may modulate mucosal inflammation following colonization with E. coli, LF82, and exposure to dextran sodium sulfate (DSS). Defined microbiota mice harboring the altered Schaedler flora (ASF) were administered SBI or hydrolyzed collagen twice daily starting 7 days prior to challenge with E. coli LF82 and continuing for the remainder of the experiment. Mice were treated with DSS for 7 days and then evaluated for evidence of local and peripheral inflammation. Igs within SBI bound multiple antigens from all eight members of the ASF and E. coli LF82 by western blot analysis. Multiple parameters of LF82/DSS-induced colitis were reduced following administration of SBI, including histological lesion scores, secretion of cytokines and chemokines from cecal biopsies, intestinal fatty acid binding protein (I-FABP) and serum amyloid A from plasma. Oral administration of SBI attenuated clinical signs of LF82/DSS-induced colitis in mice. The data are consistent with the hypothesis that SBI immunoglobulin binding of bacterial antigens in the intestinal lumen may inhibit the inflammatory cascades that contribute to IBD, thus attenuating DSS-induced colitis.

  16. Interactions between Autophagy and Inhibitory Cytokines.

    Science.gov (United States)

    Wu, Tian-Tian; Li, Wei-Min; Yao, Yong-Ming

    2016-01-01

    Autophagy is a degradative pathway that plays an essential role in maintaining cellular homeostasis. Most early studies of autophagy focused on its involvement in age-associated degeneration and nutrient deprivation. However, the immunological functions of autophagy have become more widely studied in recent years. Autophagy has been shown to be an intrinsic cellular defense mechanism in the innate and adaptive immune responses. Cytokines belong to a broad and loose category of proteins and are crucial for innate and adaptive immunity. Inhibitory cytokines have evolved to permit tolerance to self while also contributing to the eradication of invading pathogens. Interactions between inhibitory cytokines and autophagy have recently been reported, revealing a novel mechanism by which autophagy controls the immune response. In this review, we discuss interactions between autophagy and the regulatory cytokines IL-10, transforming growth factor-β, and IL-27. We also mention possible interactions between two newly discovered cytokines, IL-35 and IL-37, and autophagy.

  17. Early Death from Rabies Despite of Receiving Immunoglobulin and Vaccine

    Directory of Open Access Journals (Sweden)

    Mahmood Sadeghi

    2015-05-01

    Full Text Available Rabies is a viral disease with the high rate of mortality, which is non-curable after presenting clinical signs weather in humans or animals. Persons who are bitten by suspicious animals can be protected from rabies, in case of early referring to the health care preventive centers. However, the rate of durability and safety are questionable among those received immunoglobulin and vaccine. Here, it was reported a 57 year-old woman who was bitten by a jackal and died, despite of receiving immunoglobulin and rabies vaccine.  

  18. Intrathecal synthesis of free immunoglobulin light chains in multiple sclerosis

    DEFF Research Database (Denmark)

    Krakauer, M; Schaldemose Nielsen, H; Jensen, J

    1998-01-01

    OBJECTIVE: The detection of oligoclonal immunoglobulin free light chains (FLC) in the diagnosis of multiple sclerosis (MS) was compared to IgG isoelectric focusing. MATERIAL AND METHODS: Cerebrospinal fluid and serum samples from 69 patients with possible first attacks of MS, 50 patients with cli......OBJECTIVE: The detection of oligoclonal immunoglobulin free light chains (FLC) in the diagnosis of multiple sclerosis (MS) was compared to IgG isoelectric focusing. MATERIAL AND METHODS: Cerebrospinal fluid and serum samples from 69 patients with possible first attacks of MS, 50 patients...

  19. Bacteriostatic enterochelin-specific immunoglobulin from normal human serum

    Energy Technology Data Exchange (ETDEWEB)

    Moore, D.G.; Yancey, R.J.; Lankford, C.E.; Earhart, C.F.

    1980-02-01

    Heat-inactivated normal human serum produces iron-reversible bacteriostasis of a number of microorganisms. This inhibitory effect was abolished by adsorption of serum with ultraviolet-killed cells of species that produce the siderophore enterochelin. Bacteriostasis also was alleviated by asorption of serum with 2,3-dihydroxy-N-benzoyl-L-serine, a degradation product of enterochelin, bound to the insoluble matrix AH-Sepharose 4B. Our results indicate that enterochelin-specific immunoglobulins exist in normal human serum. These immunoglobulins may act synergistically with transferrin to effect bacteriostasis of enterochelin-producing pathogens.

  20. Immunoglobulin Concentration in Tears of Contact Lens Wearers

    OpenAIRE

    Maurya, Rajendra P.; Bhushan, Prashant; Singh, Virendra P.; Singh, Mahendra K.; Kumar, Prakash; Bhatia, Ravindra P.S.; Singh, Usha

    2014-01-01

    Purpose: To evaluate changes in the concentration of tear immunoglobulins in contact lens wearers. Methods: A total of 45 cases including 23 contact lens wearers (43 eyes) and 22 age and sex matched healthy controls having no ocular pathology were studied for immunoglobulins (IgA, IgG, IgM) in their tears by single radial immunodiffusion method. Results: Most of the cases used soft (56.6%) and semi-soft gas permeable (30.4%) contact lenses. Tear IgM was detected in only 17.4% and tear I...

  1. Adhesins of immunoglobulin-like superfamily from earthworm Eisenia foetida.

    Science.gov (United States)

    Popović, M; Hrzenjak, T; Grdisa, M; Vuković, S

    1998-05-01

    1. From the biologically active extract (G-90) isolated from the tissue homogenate of Eisenia foetida immunoglobulin-like structures were isolated and named G-90/4. 2. G-90/4 in nanogram concentrations stimulated cell proliferation more than did the original G-90. It lyses cells in microgram concentrations. 3. G-90/4 acts as an adhesion molecule between the receptors of adjacent cells. 4. The increase in proliferative activity was accompanied by the elevation of cytoplasmic protein containing tyrosine. 5. Immunohistochemical analyses confirm immunoglobulin-like transmembrane structures in the connective and muscular tissues of E. foetida.

  2. Action of (R)-sila-venlafaxine and reboxetine to antagonize cisplatin-induced acute and delayed emesis in the ferret

    International Nuclear Information System (INIS)

    Warneck, Julie B.; Cheng, Frankie H.M.; Barnes, Matthew J.; Mills, John S.; Montana, John G.; Naylor, Robert J.; Ngan, Man-P.; Wai, Man-K.; Daiss, Juergen O.; Tacke, Reinhold; Rudd, John A.

    2008-01-01

    The chemotherapeutic drug cisplatin is associated with severe gastrointestinal toxicity that can last for several days. A recent strategy to treat the nausea and emesis includes the combination of a 5-HT 3 receptor antagonist, a glucocorticoid, and an NK 1 receptor antagonist. The present studies explore the use of the selective noradrenaline reuptake inhibitors, (R)-sila-venlafaxine, (R,R)-reboxetine and (S,S)-reboxetine to prevent cisplatin (5 mg/kg, i.p.)-induced acute (0-24 h) and delayed (24-72 h) emesis in ferrets. The positive control regimen of ondansetron and dexamethasone, both at 1 mg/kg/8 h, reduced acute and delayed emesis by 100 (P 0.05). In conclusion, the studies provide the first evidence for an anti-emetic potential of noradrenaline reuptake inhibitors to reduce chemotherapy-induced acute and delayed emesis

  3. CAF01 adjuvant increases the protection conferred by a commercially available influenza split vaccine in a ferret model

    DEFF Research Database (Denmark)

    Martel, Cyril; Jensen, Trine Hammer; Nielsen, Lars Peter

    The immunogenicity and efficacy of preventive vaccines against influenza are considered suboptimal and the development of novel influenza vaccination strategies is urgently needed. Commercially available trivalent split vaccines are known to elicit mainly a humoral immune response, whereas......, we compared the immune response in ferrets vaccinated with a commercial influenza split vaccine with the same vaccine mixed with the CAF01 adjuvant and furthermore used two recently circulating H1N1 viruses for the challenge of the animals. We investigated antibody levels in serum and nasal washes...... the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6’-dibehenate, CAF01) was developed, which was proven to enhance both humoral and cell-mediated immune responses of a number of vaccine candidates. In the current study...

  4. The actions of methacholine, phenylephrine, salbutamol and histamine on mucus secretion from the ferret in-vitro trachea.

    Science.gov (United States)

    Webber, S E; Widdicombe, J G

    1987-10-01

    Methacholine, phenylephrine and histamine produced highly significant and salbutamol significant increases in the rate of mucus secretion from the ferret trachea. Methacholine, phenylephrine and histamine all produced highly significant increases in the rate of output of lysozyme, but the concentration of lysozyme in the mucus was significantly increased only by phenylephrine. Salbutamol produced no significant change in the output of lysozyme, and the concentration of lysozyme in the mucus was significantly decreased. It is concluded that methacholine, phenylephrine and histamine are potent stimulators of serous cell secretion whereas salbutamol has only a weak secretory action on these cells. Methacholine, histamine and salbutamol probably stimulate secretion from mucous cells as well as from serous cells. The increase in the concentration of lysozyme produced by phenylephrine may be due to stimulation of a fluid reabsorption mechanism.

  5. A new adjuvant enhances the protection of the commercial influenza vaccine in the ferret model

    DEFF Research Database (Denmark)

    Martel, Cyril Jean-Marie; Jensen, Trine Hammer; Nielsen, Lars P.

    challenged with H1N1 A/New Caledonia/20/99, ferrets immunized with the adjuvanted vaccine displayed a much stronger humoral response and lower viral titers than the ones that received only the regular vaccine. Gamma-interferon production, assessed by both RT-PCR and flow cytometry, and pathology studies......DDA-TDB is a cationic liposome-based adjuvant known to produce a very substantial CMI and at the same time a strong humoral response, desirable for a high number of disease targets. We tested the effect of this adjuvant when combined to a commercially available inactivated influenza vaccine. When...... on the upper and lower respiratory tract confirmed those findings. This study indicates that DDA/TDB has a strong potential to be used as an adjuvant for inactivated influenza vaccines....

  6. CAF01 adjuvant increases the protection conferred by a commercially available influenza split vaccine in a ferret model

    DEFF Research Database (Denmark)

    Martel, Cyril; Jensen, Trine Hammer; Nielsen, Lars Peter

    The immunogenicity and efficacy of preventive vaccines against influenza are considered suboptimal and the development of novel influenza vaccination strategies is urgently needed. Commercially available trivalent split vaccines are known to elicit mainly a humoral immune response, whereas...... the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6’-dibehenate, CAF01) was developed, which was proven to enhance both humoral and cell-mediated immune responses of a number of vaccine candidates. In the current study......, we compared the immune response in ferrets vaccinated with a commercial influenza split vaccine with the same vaccine mixed with the CAF01 adjuvant and furthermore used two recently circulating H1N1 viruses for the challenge of the animals. We investigated antibody levels in serum and nasal washes...

  7. Dietary intervention with serum-derived bovine immunoglobulins protects barrier function in a mouse model of colitis.

    Science.gov (United States)

    Pérez-Bosque, Anna; Miró, Lluïsa; Maijó, Mònica; Polo, Javier; Campbell, Joy; Russell, Louis; Crenshaw, Joe; Weaver, Eric; Moretó, Miquel

    2015-06-15

    Dietary supplementation with immunoglobulins from animal plasma has anti-inflammatory effects on intestinal and lung models of acute inflammation. Here, we aimed to establish whether dietary intervention with serum-derived bovine immunoglobulin (SBI) can prevent alterations in intestinal barrier function in a mouse model with a genetic predisposition to inflammatory bowel disease (IBD). Wild-type (WT) mice and mice lacking the mdr1a gene (KO) were fed diets supplemented with either SBI (2% wt/wt) or milk proteins (control diet), from day 21 (weaning) until day 56. The epithelial permeability of distal colon crypts was measured by confocal microscopy using a fluorescent marker. The expression of junctional epithelial E-cadherin and β-catenin proteins were determined by Western blot and zonula occludens-1 (ZO-1) by immunofluorescence. Mucins (MUC1, MUC2, MUC4), TFF3, cytokines (TNF-α, IFN-γ), and inducible nitric oxide synthase RNA expression were quantified by real-time PCR. SBI blocked the increase in colon crypt permeability and partially prevented the reduction in E-cadherin and ZO-1 expression that characterize the KO mouse model (both P genetic model of IBD.

  8. Development of ileal cytokine and immunoglobulin expression levels in response to early feeding in broilers and layers

    NARCIS (Netherlands)

    Simon, K.; Vries Reilingh, de G.; Kemp, B.; Lammers, A.

    2014-01-01

    Provision of feed in the immediate posthatch period may influence interaction between intestinal microbiota and immune system, and consequently immunological development of the chick. This study addressed ileal immune development in response to early feeding in 2 chicken breeds selected for

  9. CP-25 Attenuates the Activation of CD4+ T Cells Stimulated with Immunoglobulin D in Human.

    Science.gov (United States)

    Wu, Yu-Jing; Chen, Heng-Shi; Chen, Wen-Sheng; Dong, Jin; Dong, Xiao-Jie; Dai, Xing; Huang, Qiong; Wei, Wei

    2018-01-01

    Researchers have shown that the level of immunoglobulin D (IgD) is often elevated in patients with autoimmune diseases. The possible roles of IgD on the function of human T cell activation are still unclear. Paeoniflorin-6'- O -benzene sulfonate (code: CP-25), the chemistry structural modifications of paeoniflorin, was a novel drug of anti-inflammation and immunomodulation. The aims of this study were to determine if human CD4 + T cells could be activated by IgD via the IgD receptor (IgDR)-Lck pathway and whether the novel compound CP-25 could affect the activation of T cells by regulating Lck. Human CD4 + T cells were purified from peripheral blood mononuclear cells using microbeads. T cell viability and proliferation were detected by Cell Counting Kit-8 and CFSE Cell Proliferation Kit. Cytokines secreted by T cells were assessed with the Quantibody Human Inflammation Array. The binding affinity and expression of IgDR on T cells were detected by flow cytometry, and protein expression of IgDR, Lck, and P-Lck were analyzed by western blot. IgD was shown to bind to IgDR on CD4 + T cells in a concentration-dependent manner and stimulate the activation and proliferation of these cells by enhancing phosphorylation of the activating tyrosine residue of Lck (Tyr 394 ). CP-25 inhibited the IgD-stimulated activation and proliferation of CD4 + T cells, as well as the production of inflammatory cytokines; it was thus suggested that this process might be related to the downregulation of Lck (Tyr 394 ) phosphorylation. These results demonstrate that IgD amplifies the activation of CD4 + T cells, which could be mediated by Lck phosphorylation. Further, CP-25, via its ability to modulate Lck, is a novel potential therapeutic agent for the treatment of human autoimmune diseases.

  10. Dapsone inhibits IL-8 secretion from human bronchial epithelial cells stimulated with lipopolysaccharide and resolves airway inflammation in the ferret.

    Science.gov (United States)

    Kanoh, Soichiro; Tanabe, Tsuyoshi; Rubin, Bruce K

    2011-10-01

    IL-8 is an important activator and chemoattractant for neutrophils that is produced by normal human bronchial epithelial (NHBE) cells through mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) p65 pathways. Dapsone, a synthetic sulfone, is widely used to treat chronic neutrophil dermatoses. We investigated the effects of dapsone on polarized IL-8 secretion from lipopolysaccharide (LPS)-stimulated NHBE cells and further evaluated its ability to decrease LPS-induced inflammation in the ferret airway. NHBE cells were grown at air-liquid interface (ALI) to ciliated differentiation. Baseline and endotoxin (LPS)-stimulated IL-8 secretion was measured by enzyme-linked immunosorbent assay at air and basal sides with and without dapsone. Western blotting was used to determine signaling pathways. In vivo, ferrets were exposed to intratracheal LPS over a period of 5 days. Once inflammation was established, oral or nebulized dapsone was administered for 5 days. Intraepithelial neutrophil accumulation was analyzed histologically, and mucociliary transport was measured on the excised trachea. Dapsone, 1 μg/mL, did not influence unstimulated (basal) IL-8 secretion. Apical LPS stimulation induced both apical and basolateral IL-8, but basolateral LPS increased only basolateral IL-8. Dapsone inhibited polarized IL-8 secretion from ALI-conditioned cells. Dapsone also decreased LPS-induced IL-8 mRNA level. LPS led to phosphorylation of extracellular signal-regulated kinase 1/2, but not p38 MAPK or c-Jun NH(2)-terminal kinase. LPS also induced NF-κB p65 phosphorylation, an effect that was inhibited by dapsone. Both oral and aerosol dapsone decreased LPS-induced intraepithelial neutrophil accumulation, but only treatment with aerosol dapsone restored mucociliary transport to normal. Dapsone, given either systemically or as an aerosol, may be useful in treating neutrophilic airway inflammation.

  11. Transmission of a 2009 H1N1 pandemic influenza virus occurs before fever is detected, in the ferret model.

    Directory of Open Access Journals (Sweden)

    Kim L Roberts

    Full Text Available During the early phase of the 2009 influenza pandemic, attempts were made to contain the spread of the virus. Success of reactive control measures may be compromised if the proportion of transmission that occurs before overt clinical symptoms develop is high. In this study we investigated the timing of transmission of an early prototypic strain of pandemic H1N1 2009 influenza virus in the ferret model. Ferrets are the only animal model in which this can be assessed because they display typical influenza-like clinical signs including fever and sneezing after infection. We assessed transmission from infected animals to sentinels that were placed either in direct contact or in adjacent cages, the latter reflecting the respiratory droplet (RD transmission route. We found that pre-symptomatic influenza transmission occurred via both contact and respiratory droplet exposure before the earliest clinical sign, fever, developed. Three of 3 animals exposed in direct contact between day 1 and 2 after infection of the donor animals became infected, and 2/3 of the animals exposed at this time period by the RD route acquired the infection, with the third animal becoming seropositive indicating either a low level infection or significant exposure. Moreover, this efficient transmission did not temporally correlate with respiratory symptoms, such as coughs and sneezes, but rather with the peak viral titre in the nose. Indeed respiratory droplet transmission did not occur late in infection, even though this was when sneezing and coughing were most apparent. None of the 3 animals exposed at this time by the RD route became infected and these animals remained seronegative at the end of the experiment. These data have important implications for pandemic planning strategies and suggest that successful containment is highly unlikely for a human-adapted influenza virus that transmits efficiently within a population.

  12. A trivalent virus-like particle vaccine elicits protective immune responses against seasonal influenza strains in mice and ferrets.

    Directory of Open Access Journals (Sweden)

    Ted M Ross

    Full Text Available There is need for improved human influenza vaccines, particularly for older adults who are at greatest risk for severe disease, as well as to address the continuous antigenic drift within circulating human subtypes of influenza virus. We have engineered an influenza virus-like particle (VLP as a new generation vaccine candidate purified from the supernatants of Sf9 insect cells following infection by recombinant baculoviruses to express three influenza virus proteins, hemagglutinin (HA, neuraminidase (NA, and matrix 1 (M1. In this study, a seasonal trivalent VLP vaccine (TVV formulation, composed of influenza A H1N1 and H3N2 and influenza B VLPs, was evaluated in mice and ferrets for the ability to elicit antigen-specific immune responses. Animals vaccinated with the TVV formulation had hemagglutination-inhibition (HAI antibody titers against all three homologous influenza virus strains, as well as HAI antibodies against a panel of heterologous influenza viruses. HAI titers elicited by the TVV were statistically similar to HAI titers elicited in animals vaccinated with the corresponding monovalent VLP. Mice vaccinated with the TVV had higher level of influenza specific CD8+ T cell responses than a commercial trivalent inactivated vaccine (TIV. Ferrets vaccinated with the highest dose of the VLP vaccine and then challenged with the homologous H3N2 virus had the lowest titers of replicating virus in nasal washes and showed no signs of disease. Overall, a trivalent VLP vaccine elicits a broad array of immunity and can protect against influenza virus challenge.

  13. Novel methods of cytokine detection: Real-time PCR, ELISPOT, and intracellular cytokine staining

    Directory of Open Access Journals (Sweden)

    Eliza Turlej

    2009-05-01

    Full Text Available Cytokines are small hormone-like proteins that play important roles in immune system control. Cytokines regulate the proliferation and differentiation of cells and hematopoiesis and act as mediators in the inflammatory reaction. Changes in cytokine levels are found in many diseases, such as sepsis, bowel inflammatory disease, autoimmune diseases, as well as graft-versus-host disease. Cytokines levels can be detected using in vivo, in vitro, and ex vivo techniques. The level of cytokine produced can be measured by immunoenzymatic test (ELISA in supernatant after cell culture with the addition of stimulant and in plasma by techniques that measure the level of cytokine secretion in cells (e.g. immunohistochemical staining, ELISPOT, and intracellular cytokine staining, and by molecular biological methods (RPA, real-time PCR, in situ hybridization, and Northern blot. Detection of cytokine mRNA in tissues is useful in the direct determination of heterogenic populations of cytokine-producing cells. Nowadays the most frequently used methods for measuring cytokine level are ELISPOT, intracellular cytokine staining with flow cytometry detection, and real-time PCR. These methods have an important clinical role in vaccine efficacy, in viral, bacterial, and verminous diagnostics, and in determining the efficacy of cancer treatment.

  14. 21 CFR 866.5550 - Immunoglobulin (light chain specific) immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin (light chain specific... Test Systems § 866.5550 Immunoglobulin (light chain specific) immunological test system. (a) Identification. An immunoglobulin (light chain specific) immunological test system is a device that consists of...

  15. 21 CFR 866.5540 - Immunoglobulin G (Fd fragment specific) immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin G (Fd fragment specific... Test Systems § 866.5540 Immunoglobulin G (Fd fragment specific) immunological test system. (a) Identification. An immunoglobulin G (Fd fragment specific) immunological test system is a device that consists of...

  16. 21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin G (Fab fragment specific... Test Systems § 866.5520 Immunoglobulin G (Fab fragment specific) immunological test system. (a) Identification. An immunoglobulin G (Fab fragment specific) immunological test system is a device that consists...

  17. 21 CFR 866.5530 - Immunoglobulin G (Fc fragment specific) immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin G (Fc fragment specific... Test Systems § 866.5530 Immunoglobulin G (Fc fragment specific) immunological test system. (a) Identification. An immunoglobulin G (Fc fragment specific) immunological test system is a device that consists of...

  18. 21 CFR 866.5510 - Immunoglobulins A, G, M, D, and E immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulins A, G, M, D, and E immunological... Test Systems § 866.5510 Immunoglobulins A, G, M, D, and E immunological test system. (a) Identification. An immunoglobulins A, G, M, D, and E immunological test system is a device that consists of the...

  19. Modulation of cytokine production by carnitine

    Directory of Open Access Journals (Sweden)

    Nicola M. Kouttab

    1993-01-01

    Full Text Available The ability of carnitine congeners to modulate cytokine production by human peripheral blood mononuclear cells (PBMC was investigated. Modulation of cytokine production by PBMC of young (30 years of age or younger and old (70 years of age or older normal donors was first compared. The PBMC were collected over Ficoll–Hypaque and incubated in the presence of various concentrations of acetyl L-carnitine for 24 h. Subsequently the supernatants were collected and examined for cytokine production. The presence of cytokines in tissue culture supernatants was examined by ELISA. The cytokines measured included IL-1α, IL-1β, IL-2, IL-4, IL-6, TNFα, GM–CSF, and IFNγ. The results showed that at 50 μg/ml of acetyl L-carnitine the most significant response was obtained for TNFα. In this regard four of five young donors responded, but only one of five old donors responded. More recently these studies were expanded to examine the ability of L-carnitine to modulate cytokine production at higher doses, 200 and 400 μg/ml, in young donors. The results of these studies showed that in addition to TNFα, significant production of IL-1β and IL-6 was observed. These preliminary studies provide evidence that carnitine may modulate immune functions through the production of selected cytokines.

  20. Bordetella bronchiseptica antigen enhances the production of Mycoplasma hyopneumoniae antigen-specific immunoglobulin G in mice.

    Science.gov (United States)

    Yim, Seol-Hwa; Hahn, Tae-Wook; Joo, Hong-Gu

    2017-09-30

    We previously demonstrated that Bordetella ( B .) bronchiseptica antigen (Ag) showed high immunostimulatory effects on mouse bone marrow cells (BMs) while Mycoplasma ( M .) hyopneumoniae Ag showed low effects. The focus of this study was to determine if B. bronchiseptica Ag can enhance the M. hyopneumoniae Ag-specific immune response and whether the host's immune system can recognize both Ags. MTT assay results revealed that each or both Ags did not significantly change BM metabolic activity. Flow cytometry analysis using carboxyfluorescein succinimidyl ester showed that B. bronchiseptica Ag can promote the division of BMs. In cytokine and nitric oxide (NO) assays, B. bronchiseptica Ag boosted production of tumor necrosis factor-alpha in M. hyopneumoniae Ag-treated BMs, and combined treatment with both Ags elevated the level of NO in BMs compared to that from treatment of M. hyopneumoniae Ag alone. Immunoglobulin (Ig)G enzyme-linked immunosorbent assay using the sera of Ag-injected mice clearly indicated that B. bronchiseptica Ag can increase the production of M. hyopneumoniae Ag-specific IgG. This study provided information valuable in the development of M. hyopneumoniae vaccines and showed that B. bronchiseptica Ag can be used both as a vaccine adjuvant and as a vaccine Ag.

  1. Differentiation of chronic lymphocytic leukemia B cells into immunoglobulin secreting cells decreases LEF-1 expression.

    Directory of Open Access Journals (Sweden)

    Albert Gutierrez

    Full Text Available Lymphocyte enhancer binding factor 1 (LEF-1 plays a crucial role in B lineage development and is only expressed in B cell precursors as B cell differentiation into mature B and plasma cells silences its expression. Chronic lymphocytic leukemia (CLL cells aberrantly express LEF-1 and its expression is required for cellular survival. We hypothesized that modification of the differentiation status of CLL cells would result in loss of LEF-1 expression and eliminate the survival advantage provided by its aberrant expression. In this study, we first established a methodology that induces CLL cells to differentiate into immunoglobulin (Ig secreting cells (ISC using the TLR9 agonist, CpG, together with cytokines (CpG/c. CpG/c stimulation resulted in dramatic CLL cell phenotypic and morphologic changes, expression of cytoplasmic Ig, and secretion of light chain restricted Ig. CpG/c stimulation also resulted in decreased CLL cell LEF-1 expression and increased Blimp-1 expression, which is crucial for plasma cell differentiation. Further, Wnt pathway activation and cellular survival were impaired in differentiated CLL cells compared to undifferentiated CLL cells. These data support the notion that CLL can differentiate into ISC and that this triggers decreased leukemic cell survival secondary to the down regulation of LEF-1 and decreased Wnt pathway activation.

  2. High dose intravenous immunoglobulin in Rh and ABO hemolytic ...

    African Journals Online (AJOL)

    Ehab

    High dose intravenous immunoglobulin in Rh and ABO hemolytic disease of Egyptian neonates. INTRODUCTION. Hemolytic disease of the newborn (HDN) due to red cell alloimmunisation is an important cause of hyperbilirubinemia with significant morbidity in the neonatal period.1,2. Hemolytic disease of the newborn has ...

  3. Levels of serum immunoglobulins in apparently healthy children and ...

    African Journals Online (AJOL)

    olayemitoyin

    Summary: Serum levels of the immunoglobulins: IgG, IgA and IgM were determined by the single radial immunodiffusion technique of Mancini in a total of 122 apparently healthy subjects consisting of 43 children (20 males; 23 females) aged 5-12 years and 79 adults (39 males; 40 females) aged 18-65 years resident in Port ...

  4. Uptake of Colostral Immunoglobulins by the Compromised Newborn Farm Animal

    Directory of Open Access Journals (Sweden)

    Sangild PT

    2003-03-01

    Full Text Available Neonatal mortality is very high in farm animals (~10% and disease resistance is greatly influenced by an adequate passive immunisation just after birth. In piglets, foals, calves and lambs, the intestinal absorption of immunoglobulins from their mother's colostrum occurs mainly by a non-specific endocytosis of macromolecules, but the details of the absorption process, and the mechanisms regulating its cessation after 1–2 days of colostrum exposure, remain poorly understood. In both normal and 'compromised' (premature, growth-retarded, hypoxic, lethargic newborn farm animals, the intestinal capacity to absorb macromolecules is influenced by both diet- and animal-related factors. Thus, macromolecule uptake is severely reduced in response to premature birth and when macromolecules are to be absorbed from diets other than species-specific colostrum. On the other hand, fetal growth retardation, in vitro embryo production, or a stressful birth process are unlikely to reduce the ability of the intestine to absorb immunoglobulins from colostrum. More knowledge about the diet- and animal-related factors affecting intestinal immunoglobulin uptake will improve the clinical care of 'compromised' newborn farm animals. The present text gives a brief introduction to the process of intestinal immunoglobulin absorption in large farm animals and describe some recent results from the author's own studies in pigs, calves and lambs.

  5. Purification, characterization and ELISA detection of mink immunoglobulins

    DEFF Research Database (Denmark)

    Martel, Cyril Jean-Marie; Aasted, Bent

    2008-01-01

    This study describes easy purification methods for mink IgG, IgA and IgM immunoglobulins. IgG and IgM were purified from normal mink serum, while IgA was purified from mink bile from healthy animals. By SDS-polyacrylamid-gel-electrophoresis  (SDS-PAGE) and immunoblotting under reducing conditions...

  6. Pattern of intravenous immunoglobulins (IVIG) use in a pediatric ...

    African Journals Online (AJOL)

    EB

    Abstract. Background: Intravenous Immunoglobulin (IVIG) preparations are scarce biological products used for replacement or immunomodulatory effects. Guidelines have been issued by regulatory health authorities to ensure provision of the products for patients who are in severe need. Objectives: The study aimed at ...

  7. In vitro investigation of immunoglobulin treatment mechanisms in autoimmune diseases

    NARCIS (Netherlands)

    Brand, A.; Vuist, W. M.; van Schaik, I. N.; Vermeulen, M.

    1996-01-01

    High doses of immunoglobulins (IVIG) may have beneficial effects in patients with autoimmune diseases. In this review several different mechanisms of action are discussed. These mechanisms include effects on the effector phase of the immune response, on the initial steps of the immune response and

  8. Immunoglobulin G bound to ovine placenta is eluted by surgical ...

    African Journals Online (AJOL)

    Objective: To elute placental bound immunoglobulin G (IgG) in situ. Design: Laboratory based experimentation. Setting: Biological Sciences Department, The University of Newcastle Australia and the Department of Biochemistry, University of Nairobi, Kenya. Subjects: Twelve pregnant ewes 10 to 15 days before the onset of ...

  9. Unusual recovery from acute panautonomic neuropathy after immunoglobulin therapy

    NARCIS (Netherlands)

    Smit, A. A.; Vermeulen, M.; Koelman, J. H.; Wieling, W.

    1997-01-01

    A 33-year-old woman with acute idiopathic postganglionic panautonomic neuropathy experienced prompt recovery of all dysautonomic symptoms after receiving high-dose intravenous immunoglobulin therapy. Her recovery was complete within 6 months after onset of disease. This unusually rapid and complete

  10. Levels of serum immunoglobulins in apparently healthy children and ...

    African Journals Online (AJOL)

    Serum levels of the immunoglobulins: IgG, IgA and IgM were determined by the single radial immunodiffusion technique of Mancini in a total of 122 apparently healthy subjects consisting of 43 children (20 males; 23 females) aged 5-12 years and 79 adults (39 males; 40 females) aged 18-65 years resident in Port Harcourt, ...

  11. Intravenous immunoglobulin in the prevention of recurrent miscarriage

    DEFF Research Database (Denmark)

    Christiansen, Ole B; Nielsen, Henriette Svarre

    2005-01-01

    Immunological disturbances play a role in the majority of patients with recurrent miscarriage (RM) and therefore treatment with intravenous immunoglobulin (IvIg) has been tested in patients with RM in several trials. Seven placebo-controlled trials that were extremely heterogeneous with respect...

  12. Immunoglobulins against Tyrosine Nitrated Epitopes in Coronary Artery Disease

    Science.gov (United States)

    Thomson, Leonor; Tenopoulou, Margarita; Lightfoot, Richard; Tsika, Epida; Parastatidis, Ioannis; Martinez, Marissa; Greco, Todd M.; Doulias, Paschalis-Thomas; Wu, Yuping; Tang, W. H. Wilson; Hazen, Stanley L.; Ischiropoulos, Harry

    2012-01-01

    Background Several lines of evidence support a pathophysiological role of immunity in atherosclerosis. Tyrosine nitrated proteins, a footprint of oxygen and nitrogen derived oxidants generated by cells of the immune system, are enriched in atheromatous lesions and in circulation of coronary artery disease (CAD) subjects. However, the consequences of possible immune reactions triggered by the presence of nitrated proteins in subjects with clinically documented atherosclerosis have not been explored. Methods and Results Specific immunoglobulins that recognize 3-nitrotyrosine epitopes were identified in human lesions, as well as in circulation of CAD subjects. The levels of circulating immunoglobulins against 3-nitrotyrosine epitopes were quantified in CAD patients (n=374) and subjects without CAD (non CAD controls, n=313). A ten-fold increase in the mean level of circulating immunoglobulins against protein-bound 3-nitrotyrosine was documented in the CAD subjects (3.75 ± 1.8 μg antibody Eq/mL plasma vs. 0.36 ± 0.8 μg antibody Eq/mL plasma), and was strongly associated with angiographic evidence of significant CAD. Conclusions The results of this cross sectional study suggest that post-translational modification of proteins via nitration within atherosclerotic plaque-laden arteries and in circulation serve as neoepitopes for elaboration of immunoglobulins, thereby providing an association between oxidant production and the activation of the immune system in CAD. PMID:23081989

  13. Immunoglobulin A1 protease activity in Gemella haemolysans

    DEFF Research Database (Denmark)

    Lomholt, JA; Kilian, Mogens

    2000-01-01

    The purpose of this study was to determine the occurrence and nature of immunoglobulin A1 (IgA1) protease activity in members of the genus Gemella and related taxa. Among a total of 22 Gemella strains belonging to the four species Gemella haemolysans, Gemella morbillorum, Gemella sanguinis...

  14. Structure of Fc-fragment of the mouse immunoglobulin

    Czech Academy of Sciences Publication Activity Database

    Kolenko, Petr; Dohnálek, Jan; Štouračová, Renata; Skálová, Tereza; Tishchenko, Galina; Dušková, Jarmila; Hašek, Jindřich

    2005-01-01

    Roč. 12, č. 2 (2005), s. 146-147 ISSN 1211-5894. [Colloquium of Crystallographic Society : Structure. Třešť, 20.06.2005-23.06.2005] R&D Projects: GA MŠk(CZ) 1K05008 Keywords : immunoglobulin * x-ray crystallography * structure determination Subject RIV: EB - Genetics ; Molecular Biology

  15. Variations of immunoglobulins after antigenic injection in irradiated rabbit

    International Nuclear Information System (INIS)

    Servant, P.; Borgard, J.P.

    Study on the influence of irradiation upon rabbit immunoglobulins is developed. It is tried to check if the observed delay, after cephalic irradiation, in specified antibody response of injected antigen, could be in relation with a transient hypoimmunoglobulinemia in these same animals [fr

  16. Glycosylation analysis of immunoglobulin G : method development and clinical applications

    NARCIS (Netherlands)

    Selman, Maurice Henricus Johannes

    2012-01-01

    Immunoglobulin G (IgG) represents the most abundant antibody class in the human circulation. IgG consists of two heavy chains and two light chains. Parts of the heavy chains, together with the light chains, form two fragment antigen binding (Fab) moieties, whilst the remainders of the two heavy

  17. Rhesus anti-D immunoglobulin in chronic autoimmune neuropathy

    NARCIS (Netherlands)

    de Jager, AEJ; van der Hoeven, JH

    Objective - To investigate the effect of Rhesus anti-D immunoglobulin (anti-D) in patients with an autoimmune demyelinating neuropathy. Material and methods - Three patients with an autoimmune mediated neuropathy received 1000 IU anti-D weekly for 2 months. Results - Two patients worsened gradually

  18. Immunoglobulin D and cardiac amyloidosis: development and a case illustration.

    Science.gov (United States)

    Servonnet, Aurélie; Bouvier, François; Garcia Hejl, Carine; Sanmartin, Nancy; Renard, Christophe

    2016-06-01

    Amyloidosis results from extra-cellular deposition of proteins which interfere with tissue function. We report the case of a patient with pathological heart involvement which is caused by immunoglobulin D amyloidosis, and review current data on the amyloidois diagnosis and management.

  19. Immunoglobulin coating of faecal bacteria in inflammatory bowel disease

    NARCIS (Netherlands)

    van der Waaij, Laurens A.; Kroese, Frans G. M.; Visser, Annie; Nelis, Gerardus F.; Westerveld, Bram D.; Jansen, Peter L. M.; Hunter, John O.

    2004-01-01

    OBJECTIVE: An inappropriate mucosal immune response to the commensal bacterial flora may play a role in the pathogenesis of inflammatory bowel disease (IBD). In this study we determined the percentage of immunoglobulin-coated bacteria in the stools of patients and controls. METHODS: Faecal samples

  20. Immunoglobulin D Multiple Myeloma Presenting as Spontaneous Fracture.

    Science.gov (United States)

    Al Hadidi, Samer; Katato, Khalil; Bachuwa, Ghassan

    2017-01-01

    Immunoglobulin D multiple myeloma is a rare type of multiple myeloma that usually presents as bone pain, fatigue, or weight loss. We report a case of immunoglobulin D multiple myeloma in a 53-year-old Caucasian male patient with previous medical history of anaplastic oligodendroglioma status post-surgical resection who was evaluated for back pain while mowing the lawn. His physical examination showed tenderness over the lower thoracic vertebrae with no sensory or motor impairment. Initial lab investigations showed normocytic anemia and hypercalcemia with low parathyroid hormone. Magnetic resonance imaging of thoracic spine with and without contrast showed acute pathological fracture of the T12 vertebral body with enhancing soft tissue which extended into the left ventral epidural space and left T11-T12 neural foramen. Serum protein electrophoresis showed abnormal protein band in the gamma globulin. Free light chain assay showed serum free kappa which was elevated at 3,090.0 mg/L (reference range 3.3-19.4 mg/L). Immunoglobulin D was elevated at 566.0 mg/dL (reference range immunoglobulin D multiple myeloma urge clinicians to offer their patients new treatment options especially as of the earlier presentation of this subtype of multiple myeloma and the previous reports of worse prognosis.

  1. Targeting lentiviral vectors to antigen-specific immunoglobulins.

    Science.gov (United States)

    Ziegler, Leslie; Yang, Lili; Joo, Kye il; Yang, Haiguang; Baltimore, David; Wang, Pin

    2008-09-01

    Gene transfer into B cells by lentivectors can provide an alternative approach to managing B lymphocyte malignancies and autoreactive B cell-mediated autoimmune diseases. These pathogenic B cell populations can be distinguished by their surface expression of monospecific immunoglobulin. Development of a novel vector system to deliver genes to these specific B cells could improve the safety and efficacy of gene therapy. We have developed an efficient method to target lentivectors to monospecific immunoglobulin-expressing cells in vitro and in vivo. We were able to incorporate a model antigen CD20 and a fusogenic protein derived from the Sindbis virus as two distinct molecules into the lentiviral surface. This engineered vector could specifically bind to cells expressing surface immunoglobulin recognizing CD20 (alphaCD20), resulting in efficient transduction of target cells in a cognate antigen-dependent manner in vitro, and in vivo in a xenografted tumor model. Tumor suppression was observed in vivo, using the engineered lentivector to deliver a suicide gene to a xenografted tumor expressing alphaCD20. These results show the feasibility of engineering lentivectors to target immunoglobulin- specific cells to deliver a therapeutic effect. Such targeting lentivectors also could potentially be used to genetically mark antigen-specific B cells in vivo to study their B cell biology.

  2. Acute phase proteins and immunoglobulin classes in newly ...

    African Journals Online (AJOL)

    Background: No single organic cause has been found for schizophrenia and its management has been difficult. More so, there are few data on the immune parameters of Nigerian schizophrenic patients on drug treatment and those that are not on treatment. Methodology: This study determines the levels of immunoglobulin

  3. Bacteremia and immunoglobulin classes in Nigerian women with ...

    African Journals Online (AJOL)

    Apart from antiphospholipid- and thyroid- autoantibodies which were reported as underlying causes of recurrent pregnancy loss, specific IgG to patermal MHC and Rh was proposed. This raises the possibility of other classes of immunoglobulin in recurrent abortion. Twenty-four pregnant women with recurrent abortion ...

  4. Haemolytic anaemia as a complication to intravenous immunoglobulin infusion

    DEFF Research Database (Denmark)

    Markvardsen, Lars Høj; Harbo, Thomas; Christiansen, Ingelise

    performed before and two weeks after infusion of IVIg. Following treatment blood haemoglobin declined from 8.6±0.8 to 8.1±1.3mmol/l, p... naive patients are susceptible to develop haemolysis. Haemolytic anaemia is a severe side effect that seems to be more frequent after immunoglobulin infusions than previously recognized....

  5. serum immunoglobulin levels in white, asiatic and bantu blood donors

    African Journals Online (AJOL)

    all assays were calculated as a percentage of the mean of. TABLE I. RESULTS OF IMMUNOGLOBULIN ASSAYS OF tOO WHITE, tOO ASIATIC AND 100 BANTU DONORS, EXPRESSED AS A. PERCENTAGE OF A CONTROL SERUM. Parameter. Range. Mean. Variance. Standard deviation. CoefI. of variation.

  6. Cell phenotypes, immunoglobulins and complement in lesions of ...

    African Journals Online (AJOL)

    ... stained positive for CD68. Type III reaction consisted of a discrete epithelioid granuloma without wellformed grains. IgG, IgM and C3 were found on the surface of the grain and the hyphae . Keywords: Madurella mycetomatis lesion, cell phenotypes, immunoglobulins, complement. Sudanese Journal of Dermatology Vol.

  7. Pattern of intravenous immunoglobulins (IVIG) use in a pediatric ...

    African Journals Online (AJOL)

    Background: Intravenous Immunoglobulin (IVIG) preparations are scarce biological products used for replacement or immunomodulatory effects. Guidelines have been issued by regulatory health authorities to ensure provision of the products for patients who are in severe need. Objectives: The study aimed at description of ...

  8. Mechanism of immunoglobulin G4 Fab-arm exchange

    NARCIS (Netherlands)

    Rispens, Theo; Ooijevaar-de Heer, Pleuni; Bende, Onno; Aalberse, Rob C.

    2011-01-01

    Immunoglobulin G (IgG) antibodies are symmetrical molecules that may be regarded as covalent dimers of 2 half-molecules, each consisting of a light chain and a heavy chain. Human IgG4 is an unusually dynamic antibody, with half-molecule exchange ("Fab-arm exchange") resulting in asymmetrical,

  9. Immunoglobulin G for patients with necrotising soft tissue infection (INSTINCT)

    DEFF Research Database (Denmark)

    Madsen, Martin B.; Hjortrup, Peter B.; Hansen, Marco B.

    2017-01-01

    Purpose: The aim of the INSTINCT trial was to assess the effect of intravenous polyspecific immunoglobulin G (IVIG) compared with placebo on self-reported physical function in intensive care unit (ICU) patients with necrotising soft tissue infection (NSTI). Methods: We randomised 100 patients wit...

  10. Cytokines: applications in domestic food animals.

    Science.gov (United States)

    Blecha, F

    1991-01-01

    Cytokines such as human, bovine, and porcine interferons and human and bovine interleukin-1 and interleukin-2 have been used in vivo in cattle and pigs. Colony-stimulating factors and tumor necrosis factor alpha have been evaluated in vitro in food animals. Studies to evaluate cytokines in domestic food animals have shown that specific and nonspecific immunomodulation is possible in immunosuppressed or pathogen-exposed animals. Cytokine prophylaxis or therapy in food animals may have the greatest potential for control of respiratory disease and mastitis.

  11. Cytokines in Radiobiological Responses: A Review

    Science.gov (United States)

    Schaue, Dörthe; Kachikwu, Evelyn L.; McBride, William H.

    2013-01-01

    Cytokines function in many roles that are highly relevant to radiation research. This review focuses on how cytokines are structurally organized, how they are induced by radiation, and how they orchestrate mesenchymal, epithelial and immune cell interactions in irradiated tissues. Pro-inflammatory cytokines are the major components of immediate early gene programs and as such can be rapidly activated after tissue irradiation. They converge with the effects of ionizing radiation in that both generate free radicals including reactive oxygen and nitrogen species (ROS/RNS). “Self” molecules secreted or released from cells after irradiation feed the same paradigm by signaling for ROS and cytokine production. As a result, multilayered feedback control circuits can be generated that perpetuate the radiation tissue damage response. The pro-inflammatory phase persists until such times as perceived challenges to host integrity are eliminated. Antioxidant, anti-inflammatory cytokines then act to restore homeostasis. The balance between pro-inflammatory and anti-inflammatory forces may shift to and fro for a long time after radiation exposure, creating waves as the host tries to deal with persisting pathogenesis. Individual cytokines function within socially interconnected groups to direct these integrated cellular responses. They hunt in packs and form complex cytokine networks that are nested within each other so as to form mutually reinforcing or antagonistic forces. This yin-yang balance appears to have redox as a fulcrum. Because of their social organization, cytokines appear to have a considerable degree of redundancy and it follows that an elevated level of a specific cytokine in a disease situation or after irradiation does not necessarily implicate it causally in pathogenesis. In spite of this, “driver” cytokines are emerging in pathogenic situations that can clearly be targeted for therapeutic benefit, including in radiation settings. Cytokines can greatly

  12. Characterization of the 2009 pandemic A/Beijing/501/2009 H1N1 influenza strain in human airway epithelial cells and ferrets.

    Directory of Open Access Journals (Sweden)

    Penghui Yang

    Full Text Available BACKGROUND: A novel 2009 swine-origin influenza A H1N1 virus (S-OIV H1N1 has been transmitted among humans worldwide. However, the pathogenesis of this virus in human airway epithelial cells and mammals is not well understood. METHODOLOGY/PRINCIPAL FINDING: In this study, we showed that a 2009 A (H1N1 influenza virus strain, A/Beijing/501/2009, isolated from a human patient, caused typical influenza-like symptoms including weight loss, fluctuations in body temperature, and pulmonary pathological changes in ferrets. We demonstrated that the human lung adenocarcinoma epithelial cell line A549 was susceptible to infection and that the infected cells underwent apoptosis at 24 h post-infection. In contrast to the seasonal H1N1 influenza virus, the 2009 A (H1N1 influenza virus strain A/Beijing/501/2009 induced more cell death involving caspase-3-dependent apoptosis in A549 cells. Additionally, ferrets infected with the A/Beijing/501/2009 H1N1 virus strain exhibited increased body temperature, greater weight loss, and higher viral titers in the lungs. Therefore, the A/Beijing/501/2009 H1N1 isolate successfully infected the lungs of ferrets and caused more pathological lesions than the seasonal influenza virus. Our findings demonstrate that the difference in virulence of the 2009 pandemic H1N1 influenza virus and the seasonal H1N1 influenza virus in vitro and in vivo may have been mediated by different mechanisms. CONCLUSION/SIGNIFICANCE: Our understanding of the pathogenesis of the 2009 A (H1N1 influenza virus infection in both humans and animals is broadened by our findings that apoptotic cell death is involved in the cytopathic effect observed in vitro and that the pathological alterations in the lungs of S-OIV H1N1-infected ferrets are much more severe.

  13. Th17 cytokines induce pro-fibrotic cytokines release from human eosinophils

    Science.gov (United States)

    2013-01-01

    Background Subepithelial fibrosis is one of the most critical structural changes affecting bronchial airway function during asthma. Eosinophils have been shown to contribute to the production of pro-fibrotic cytokines, TGF-β and IL-11, however, the mechanism regulating this process is not fully understood. Objective In this report, we investigated whether cytokines associated with inflammation during asthma may induce eosinophils to produce pro-fibrotic cytokines. Methods Eosinophils were isolated from peripheral blood of 10 asthmatics and 10 normal control subjects. Eosinophils were stimulated with Th1, Th2 and Th17 cytokines and the production of TGF-β and IL-11 was determined using real time PCR and ELISA assays. Results The basal expression levels of eosinophil derived TGF-β and IL-11 cytokines were comparable between asthmatic and healthy individuals. Stimulating eosinophils with Th1 and Th2 cytokines did not induce expression of pro-fibrotic cytokines. However, stimulating eosinophils with Th17 cytokines resulted in the enhancement of TGF-β and IL-11 expression in asthmatic but not healthy individuals. This effect of IL-17 on eosinophils was dependent on p38 MAPK activation as inhibiting the phosphorylation of p38 MAPK, but not other kinases, inhibited IL-17 induced pro-fibrotic cytokine release. Conclusions Th17 cytokines might contribute to airway fibrosis during asthma by enhancing production of eosinophil derived pro-fibrotic cytokines. Preventing the release of pro-fibrotic cytokines by blocking the effect of Th17 cytokines on eosinophils may prove to be beneficial in controlling fibrosis for disorders with IL-17 driven inflammation such as allergic and autoimmune diseases. PMID:23496774

  14. The immunoglobulin heavy chain locus in the platypus (Ornithorhynchus anatinus).

    Science.gov (United States)

    Gambón-Deza, F; Sánchez-Espinel, C; Magadán-Mompó, S

    2009-08-01

    Immunoglobulins loci in mammals are well known to be organized within a translocon, however their origin remains unresolved. Four of the five classes of immunoglobulins described in humans and rodents (immunoglobulins M, G, E and A-IgM, IgG, IgE and IgA) were found in marsupials and monotremes (immunoglobulin D-IgD was not found) thus showing that the genomic structure of antibodies in mammals has remained constant since its origin. We have recently described the genomic organization of the immunoglobulin heavy chain locus in reptiles (IGHM, IGHD and IGHY). These data and the characterization of the IGH locus in platypus (Ornithorhynchus anatinus), allow us to elucidate the changes that took place in this genomic region during evolution from reptile to mammal. Thus, by using available genome data, we were able to detect that platypus IGH locus contains reptilian and mammalian genes. Besides having an IGHD that is very similar to the one in reptiles and an IGHY, they also present the mammal specific antibody genes IGHG and IGHE, in addition to IGHA. We also detected a pseudogene that originated by recombination between the IGHD and the IGHM (similar to the IGHD2 found in Eublepharis macularius). The analysis of the IGH locus in platypus shows that IGHY was duplicated, firstly by evolving into IGHE and then into IGHG. The IGHA of the platypus has a complex origin, and probably arose by a process of recombination between the IGHM and the IGHY. We detected about 44 VH genes (25 were already described), most of which comprise a single group. When we compared these VH genes with those described in Anolis carolinensis, we find that there is an evolutionary relationship between the VH genes of platypus and the reptilian Group III genes. These results suggest that a fast VH turnover took place in platypus and this gave rise to a family with a high VH gene number and the disappearance of the earlier VH families.

  15. Correlation of cutaneous sensitivity and cytokine response in children with asthma

    Directory of Open Access Journals (Sweden)

    Meenu Singh

    2017-01-01

    Full Text Available Background: Food allergy occurs in a significant portion of pediatric asthma. Various cells and their mediators/cytokines play a pivotal role in orchestrating the airway inflammatory response in asthma. Objective: To study the cutaneous hypersensitivity, Th1, Th2, and Th17 response of pediatric population with asthma and genetic predisposition to atopy, by determining total immunoglobulin E (IgE level in response to various food allergens. Materials and Methods: Fifty asthmatic children with a history of worsening symptoms by various food allergens (study group and twenty healthy children (control group were included. Food allergy was assessed through skin prick test (SPT of various food allergens. Total serum IgE level was measured by sandwich ELISA, and T-cell (Th1, Th2, and Th17-dependent cytokines were measured by flow cytometry. Results: All 50 asthmatic children in the study group showed SPT positivity against various food allergens (rice = 17; banana, fish and groundnut = 10; wheat = 9; milk and orange = 7; egg = 6; and mango = 4. The average total IgE level in the study group was 316.8 ± 189.8 IU/mL. A significant positive correlation of total IgE with interleukin 17 (IL-17 (r = 0.796; P < 0.0001, IL-13 (r = 0.383; P = 0.01, and IL-4 (r = 0.263; P = 0.043 level was noted. A significant negative correlation of total IgE was noted with interferon gamma (r = −0.5823; P < 0.0001 and IL-10 (r = −0.4474; P < 0.001 level and the duration of breastfeeding (r = −0.31, P = 0.03. Conclusions: The present study found a positive correlation between total serum IgE level and Th2, Th17 cytokines in a pediatric population with asthma. A significant negative correlation was found between the duration of breastfeeding and the cytokines.

  16. Anti-cytokine autoantibodies suggest pathogenetic links with autoimmune regulator deficiency in humans and mice

    Science.gov (United States)

    Kärner, J.; Meager, A.; Laan, M.; Maslovskaja, J.; Pihlap, M.; Remm, A.; Juronen, E.; Wolff, A. S. B.; Husebye, E. S.; Podkrajšek, K. T.; Bratanic, N.; Battelino, T.; Willcox, N.; Peterson, P.; Kisand, K.

    2013-01-01

    Summary Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a recessive disorder resulting from mutations in the autoimmune regulator (AIRE). The patients' autoantibodies recognize not only multiple organ-specific targets, but also many type I interferons (IFNs) and most T helper type 17 (Th17) cell-associated cytokines, whose biological actions they neutralize in vitro. These anti-cytokine autoantibodies are highly disease-specific: otherwise, they have been found only in patients with thymomas, tumours of thymic epithelial cells that fail to express AIRE. Moreover, autoantibodies against Th17 cell-associated cytokines correlate with chronic mucocutaneous candidiasis in both syndromes. Here, we demonstrate that the immunoglobulin (Ig)Gs but not the IgAs in APECED sera are responsible for neutralizing IFN-ω, IFN-α2a, interleukin (IL)-17A and IL-22. Their dominant subclasses proved to be IgG1 and, surprisingly, IgG4 without IgE, possibly implicating regulatory T cell responses and/or epithelia in their initiation in these AIRE-deficiency states. The epitopes on IL-22 and IFN-α2a appeared mainly conformational. We also found mainly IgG1 neutralizing autoantibodies to IL-17A in aged AIRE-deficient BALB/c mice – the first report of any target shared by these human and murine AIRE-deficiency states. We conclude that autoimmunization against cytokines in AIRE deficiency is not simply a mere side effect of chronic mucosal Candida infection, but appears to be related more closely to disease initiation. PMID:23379432

  17. Molecular Analysis of Activation-Induced Cytidine Deaminase Gene in Immunoglobulin-E Deficient Patients

    Directory of Open Access Journals (Sweden)

    Sergio Roa

    2008-01-01

    Full Text Available Understanding how class switch recombination (CSR is regulated to produce immunoglobulin E (IgE has become fundamental because of the dramatic increase in the prevalence of IgE-mediated hypersensitivity reactions. CSR requires the induction of the enzyme AICDA in B cells. Mutations in AICDA have been linked to Hyper-IgM syndrome (HIGM2, which shows absence of switching to IgE as well as to IgG and IgA. Although isolated IgE deficiency is a rare entity, here we show some individuals with normal serum IgM, IgG, and IgA levels that had undetectable total serum IgE levels. We have analyzed the AICDA gene in these individuals to determine if there are mutations in AICDA that could lead to selective IgE deficiency. Conformational sensitive gel electrophoresis (CSGE and sequencing analysis of AICDA coding sequences demonstrated sequence heterogeneity due to 5923A/G and 7888C/T polymorphisms, but did not reveal any novel mutation that might explain the selective IgE deficit.

  18. Effects of Ramadan fasting on serum immunoglobulin G and M, and salivary immunoglobulin A concentrations.

    Science.gov (United States)

    Develioglu, Omer Necati; Kucur, Mine; Ipek, Havva Duru; Celebi, Saban; Can, Gunay; Kulekci, Mehmet

    2013-04-01

    To investigate the effects of Ramadan fasting on serum concentrations of immunoglobulin (Ig)G and IgM, and salivary IgA concentrations. Blood and saliva samples were collected one week before and during the last week of Ramadan from healthy male volunteers. Albumin, total lymphocyte count, electrolytes, and IgG and IgM concentrations were determined in serum; salivary IgA concentrations were measured. Anthropometric measurements were also recorded. Samples were collected from 35 subjects (mean age 35.86 years, range 20-59 years). Weight, body mass index, albumin levels and the nutritional risk index decreased significantly during Ramadan fasting compared with before fasting. In addition, Na(+) and Cl(-) electrolyte levels were significantly decreased during Ramadan. Serum IgG concentrations decreased significantly during Ramadan compared with before fasting, but were still within the normal range. Salivary IgA concentrations also decreased significantly, whereas serum IgM levels did not change. Lymphocyte numbers increased significantly, but there was no correlation between Ig levels and lymphocyte count. Ramadan fasting did not result in severe immunological disturbances.

  19. Mature IgM-expressing plasma cells sense antigen and develop competence for cytokine production upon antigenic challenge

    Science.gov (United States)

    Blanc, Pascal; Moro-Sibilot, Ludovic; Barthly, Lucas; Jagot, Ferdinand; This, Sébastien; de Bernard, Simon; Buffat, Laurent; Dussurgey, Sébastien; Colisson, Renaud; Hobeika, Elias; Fest, Thierry; Taillardet, Morgan; Thaunat, Olivier; Sicard, Antoine; Mondière, Paul; Genestier, Laurent; Nutt, Stephen L.; Defrance, Thierry

    2016-01-01

    Dogma holds that plasma cells, as opposed to B cells, cannot bind antigen because they have switched from expression of membrane-bound immunoglobulins (Ig) that constitute the B-cell receptor (BCR) to production of the secreted form of immunoglobulins. Here we compare the phenotypical and functional attributes of plasma cells generated by the T-cell-dependent and T-cell-independent forms of the hapten NP. We show that the nature of the secreted Ig isotype, rather than the chemical structure of the immunizing antigen, defines two functionally distinct populations of plasma cells. Fully mature IgM-expressing plasma cells resident in the bone marrow retain expression of a functional BCR, whereas their IgG+ counterparts do not. Antigen boost modifies the gene expression profile of IgM+ plasma cells and initiates a cytokine production program, characterized by upregulation of CCL5 and IL-10. Our results demonstrate that IgM-expressing plasma cells can sense antigen and acquire competence for cytokine production upon antigenic challenge. PMID:27924814

  20. Matrix-M Adjuvated Seasonal Virosomal Influenza Vaccine Induces Partial Protection in Mice and Ferrets against Avian H5 and H7 Challenge.

    Directory of Open Access Journals (Sweden)

    Freek Cox

    Full Text Available There is a constant threat of zoonotic influenza viruses causing a pandemic outbreak in humans. It is virtually impossible to predict which virus strain will cause the next pandemic and it takes a considerable amount of time before a safe and effective vaccine will be available once a pandemic occurs. In addition, development of pandemic vaccines is hampered by the generally poor immunogenicity of avian influenza viruses in humans. An effective pre-pandemic vaccine is therefore required as a first line of defense. Broadening of the protective efficacy of current seasonal vaccines by adding an adjuvant may be a way to provide such first line of defense. Here we evaluate whether a seasonal trivalent virosomal vaccine (TVV adjuvated with the saponin-based adjuvant Matrix-M (MM can confer protection against avian influenza H5 and H7 virus strains in mice and ferrets. We demonstrate that mice were protected from death against challenges with H5N1 and H7N7, but that the protection was not complete as evidenced by severe clinical signs. In ferrets, protection against H7N9 was not observed. In contrast, reduced upper and lower respiratory tract viral loads and reduced lung pathology, was achieved in H5N1 challenged ferrets. Together these results suggest that, at least to some extent, Matrix-M adjuvated seasonal virosomal influenza vaccine can serve as an interim measure to decrease morbidity and mortality associated with a pandemic outbreak.

  1. Immunoglobulin concentration in blood serum of postcolostral calves: Ratio between immunoglobulin level and appearance of enzootic pneumonia

    Directory of Open Access Journals (Sweden)

    Jonić Branko

    2007-01-01

    Full Text Available The timely supply of newborn calves with optimal quantities of colostrum has a key role in the process of immune protection in the early phase of their lives. Passively acquired antibodies can protect the digestive organs from infection caused by E.coli bacteria, and it seems also from the appearance of diseases of the respiratory tract. These examinations were performed on a cattle farm where bronchopneumonia was one of the most significant health problems, and a group of 39 calves were selected for the investigations. The calves were fed with their mothers’ colostrum after birth, and then with collective milk. Immunoglobulin concentration was determined in blood samples taken during the postcolostral period, with the method using zinc-sulphate. At the age of 40 days, the calves were administered a polyvalent inactivated vaccine, and revaccinated 20 days after that (Vibak, Veterinary Department Subotica. In 74.34% calves, the immunoglobulin G concentration ranged from 26 to 40 g/l. In 25.66% calves, the immunoglobulin concentration was lower, from 8 to 25 g/l. The calves found to have a lower concentration of immunoglobulin in blood contracted bronchopneumonia more frequently, and the outcome of the disease in some cases was mortality, even.

  2. Studies on the association between immunoglobulin E autoreactivity and immunoglobulin E-dependent histamine-releasing factors

    NARCIS (Netherlands)

    Budde, Ilona Kleine; de Heer, Pleuni G.; Natter, Susanne; Mahler, Vera; van der Zee, Jaring S.; Valenta, Rudolf; Aalberse, Rob C.

    2002-01-01

    It has been reported that serum immunoglobulin E (IgE) from certain atopic patients can sensitize basophils to release histamine in response to IgE-dependent histamine-releasing factors (HRFs). It has also been shown that patients suffering from severe forms of atopy may contain IgE autoantibodies.

  3. Successful Treatment of Rotavirus-induced Diarrhoea in Suckling Mice with Egg Yolk Immunoglobulin

    Science.gov (United States)

    Sarker, Shafiqul A.; Pant, Neha; Juneja, Lekh R.; Hammarström, Lennart

    2007-01-01

    The role of specific immunoglobulins at mucosal sites in imparting protection against disease, such as rotavirus-associated diarrhoea, is well-established. Oral immunoglobulin therapy with egg yolk-derived antirotavirus immunoglobulins has previously been shown to achieve moderate therapeutic effect in diarrhoea due to rotavirus in a clinical trial. Here, data on the therapeutic potential of the same immunoglobulin preparation in an infant mouse model of rotavirus-induced diarrhoea is presented. The use of an animal model has allowed therapy to be evaluated with higher doses of immunoglobulins and has suggested that an improved therapeutic effect can be achieved by increasing the dose in the clinical setting. PMID:18402190

  4. Dynamical Systems, Cytokine Storms, and Blood Filtration

    Science.gov (United States)

    Foster, Glenn; Hubler, Alfred

    2008-03-01

    Various infections and non-infectious diseases can trigger immune cells and the proteins (cytokines) the cells use to communicate with each other to be caught in a positive feedback loop; this ``cytokine storm'' is frequently fatal. By examining the network of cytokine-immune cell interactions we will illustrate why anti-mediator drugs have been generally ineffective in stopping this feedback. A more effective approach may be to try and reduce interactions by dampening many signals at once by filtering the cytokines out of the blood directly (think dialysis). We will argue that feedback on an out of control nonlinear dynamical system is easier to understand than its normal healthy state and apply filtration to a toy model of immune response.

  5. Overexpression of the Cytokine BAFF and Autoimmunity Risk.

    Science.gov (United States)

    Steri, Maristella; Orrù, Valeria; Idda, M Laura; Pitzalis, Maristella; Pala, Mauro; Zara, Ilenia; Sidore, Carlo; Faà, Valeria; Floris, Matteo; Deiana, Manila; Asunis, Isadora; Porcu, Eleonora; Mulas, Antonella; Piras, Maria G; Lobina, Monia; Lai, Sandra; Marongiu, Mara; Serra, Valentina; Marongiu, Michele; Sole, Gabriella; Busonero, Fabio; Maschio, Andrea; Cusano, Roberto; Cuccuru, Gianmauro; Deidda, Francesca; Poddie, Fausto; Farina, Gabriele; Dei, Mariano; Virdis, Francesca; Olla, Stefania; Satta, Maria A; Pani, Mario; Delitala, Alessandro; Cocco, Eleonora; Frau, Jessica; Coghe, Giancarlo; Lorefice, Lorena; Fenu, Giuseppe; Ferrigno, Paola; Ban, Maria; Barizzone, Nadia; Leone, Maurizio; Guerini, Franca R; Piga, Matteo; Firinu, Davide; Kockum, Ingrid; Lima Bomfim, Izaura; Olsson, Tomas; Alfredsson, Lars; Suarez, Ana; Carreira, Patricia E; Castillo-Palma, Maria J; Marcus, Joseph H; Congia, Mauro; Angius, Andrea; Melis, Maurizio; Gonzalez, Antonio; Alarcón Riquelme, Marta E; da Silva, Berta M; Marchini, Maurizio; Danieli, Maria G; Del Giacco, Stefano; Mathieu, Alessandro; Pani, Antonello; Montgomery, Stephen B; Rosati, Giulio; Hillert, Jan; Sawcer, Stephen; D'Alfonso, Sandra; Todd, John A; Novembre, John; Abecasis, Gonçalo R; Whalen, Michael B; Marrosu, Maria G; Meloni, Alessandra; Sanna, Serena; Gorospe, Myriam; Schlessinger, David; Fiorillo, Edoardo; Zoledziewska, Magdalena; Cucca, Francesco

    2017-04-27

    Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways. Using case-control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus-specific association testing in systemic lupus erythematosus (SLE). Extensive phenotyping of quantitative immune variables, sequence-based fine mapping, cross-population and cross-phenotype analyses, and gene-expression studies were used to identify the causal variant and elucidate its mechanism of action. Signatures of positive selection were also investigated. A variant in TNFSF13B, encoding the cytokine and drug target B-cell activating factor (BAFF), was associated with multiple sclerosis as well as SLE. The disease-risk allele was also associated with up-regulated humoral immunity through increased levels of soluble BAFF, B lymphocytes, and immunoglobulins. The causal variant was identified: an insertion-deletion variant, GCTGT→A (in which A is the risk allele), yielded a shorter transcript that escaped microRNA inhibition and increased production of soluble BAFF, which in turn up-regulated humoral immunity. Population genetic signatures indicated that this autoimmunity variant has been evolutionarily advantageous, most likely by augmenting resistance to malaria. A TNFSF13B variant was associated with multiple sclerosis and SLE, and its effects were clarified at the population, cellular, and molecular levels. (Funded by the Italian Foundation for Multiple Sclerosis and others.).

  6. Eosinophil cytokines: Emerging roles in immunity

    Directory of Open Access Journals (Sweden)

    Paige eLacy

    2014-11-01

    Full Text Available Eosinophils derive from the bone marrow and circulate at low levels in the blood in healthy individuals. These granulated cells preferentially leave the circulation and marginate to tissues, where they are implicated in the regulation of innate and adaptive immunity. In diseases such as allergic inflammation, eosinophil numbers escalate markedly in the blood and tissues where inflammatory foci are located. Eosinophils possess a range of immunomodulatory factors that are released upon cell activation, including over 35 cytokines, growth factors, and chemokines. Unlike T and B cells, eosinophils can rapidly release cytokines within minutes in response to stimulation. While some cytokines are stored as preformed mediators in crystalloid granules and secretory vesicles, eosinophils are also capable of undergoing de novo synthesis and secretion of these immunological factors. Some of the molecular mechanisms that coordinate the final steps of cytokine secretion are hypothesized to involve binding of membrane fusion complexes comprised of soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs. These intracellular receptors regulate the release of granules and vesicles containing a range of secreted proteins, among which are cytokines and chemokines. Emerging evidence from both human and animal model-based research has suggested an active participation of eosinophils in several physiological/pathological processes such as immunomodulation and tissue remodeling. The observed eosinophil effector functions in health and disease implicate eosinophil cytokine secretion as a fundamental immunoregulatory process. The focus of this review is to describe the cytokines, growth factors, and chemokines that are elaborated by eosinophils, and to illustrate some of the intracellular events leading to the release of eosinophil-derived cytokines.

  7. Gene expression profiling in peripheral blood mononuclear cells of patients with common variable immunodeficiency: modulation of adaptive immune response following intravenous immunoglobulin therapy.

    Directory of Open Access Journals (Sweden)

    Marzia Dolcino

    Full Text Available BACKGROUND: Regular intravenous immunoglobulin treatment is used to replace antibody deficiency in primary immunodeficiency diseases; however the therapeutic effect seems to be related not only to antibody replacement but also to an active role in the modulation of the immune response. Common variable immunodeficiency is the most frequent primary immunodeficiency seen in clinical practice. METHODS: We have studied the effect of intravenous immunoglobulin replacement in patients with common variable immunodeficiency by evaluating the gene-expression profiles from Affimetrix HG-U133A. Some of the gene array results were validated by real time RT-PCR and by the measurement of circulating cytokines and chemokines by ELISA. Moreover we performed FACS analysis of blood mononuclear cells from the patients enrolled in the study. RESULTS: A series of genes involved in innate and acquired immune responses were markedly up- or down-modulated before therapy. Such genes included CD14, CD36, LEPR, IRF-5, RGS-1, CD38, TNFRSF25, IL-4, CXCR4, CCR3, IL-8. Most of these modulated genes showed an expression similar to that of normal controls after immunoglobulin replacement. Real time RT-PCR of selected genes and serum levels of IL-4, CXCR4 before and after therapy changed accordingly to gene array results. Interestingly, serum levels of IL-8 remained unchanged, as the corresponding gene, before and after treatment. FACS analysis showed a marked decrease of CD8+T cells and an increase of CD4+T cells following treatment. Moreover we observed a marked increase of CD23⁻CD27⁻IgM⁻IgG⁻ B cells (centrocytes. CONCLUSIONS: Our results are in accordance with previous reports and provide further support to the hypothesis that the benefits of intravenous immunoglobulin therapy are not only related to antibody replacement but also to its ability to modulate the immune response in common variable immunodeficiency.

  8. A conserved gene family encodes transmembrane proteins with fibronectin, immunoglobulin and leucine-rich repeat domains (FIGLER

    Directory of Open Access Journals (Sweden)

    Haga Christopher L

    2007-09-01

    Full Text Available Abstract Background In mouse the cytokine interleukin-7 (IL-7 is required for generation of B lymphocytes, but human IL-7 does not appear to have this function. A bioinformatics approach was therefore used to identify IL-7 receptor related genes in the hope of identifying the elusive human cytokine. Results Our database search identified a family of nine gene candidates, which we have provisionally named fibronectin immunoglobulin leucine-rich repeat (FIGLER. The FIGLER 1–9 genes are predicted to encode type I transmembrane glycoproteins with 6–12 leucine-rich repeats (LRR, a C2 type Ig domain, a fibronectin type III domain, a hydrophobic transmembrane domain, and a cytoplasmic domain containing one to four tyrosine residues. Members of this multichromosomal gene family possess 20–47% overall amino acid identity and are differentially expressed in cell lines and primary hematopoietic lineage cells. Genes for FIGLER homologs were identified in macaque, orangutan, chimpanzee, mouse, rat, dog, chicken, toad, and puffer fish databases. The non-human FIGLER homologs share 38–99% overall amino acid identity with their human counterpart. Conclusion The extracellular domain structure and absence of recognizable cytoplasmic signaling motifs in members of the highly conserved FIGLER gene family suggest a trophic or cell adhesion function for these molecules.

  9. Suspected idiopathic sclerosing orbital inflammation presenting as immunoglobulin G4-related disease: a case report

    Directory of Open Access Journals (Sweden)

    Nakamura Noriko

    2011-09-01

    Full Text Available Abstract Introduction Idiopathic sclerosing orbital inflammation is a rare and ill-defined heterogeneous entity, and a distinct subset of orbital inflammation. Recently, attention has been focused on immunoglobulin G4-related disease complicated with fibrotic changes in some other organs with high serum immunoglobulin G4 levels. This report presents a case of suspected idiopathic sclerosing orbital inflammation complicated with high serum immunoglobulin G4 levels. Case presentation An 82-year-old Japanese woman had a 30-year history of chronic thyroiditis. She experienced right ptosis and eyelid swelling. These symptoms gradually developed over five years. The clinical and radiographic findings suggested that our patient had idiopathic sclerosing orbital inflammation. We were unable to obtain our patient's consent to perform a biopsy. While the serum immunoglobulin G level was within the normal limits, the serum immunoglobulin G4 level was significantly elevated. The serum immunoglobulin G4 levels decreased after the administration of oral prednisolone at a daily dose of 20 mg. In addition, the swelling and ptosis of the right upper eyelid disappeared gradually after four weeks. Our patient was then suspected to have idiopathic sclerosing orbital inflammation complicated with immunoglobulin G4-related disease and chronic thyroiditis. Conclusion An orbital pseudotumor of this type is indicative of idiopathic sclerosing orbital inflammation immunoglobulin G4-related disease. Immunoglobulin G4 may thus be considered a subclass of immunoglobulin G when the serum immunoglobulin G level is within normal limits.

  10. Competitive Fitness of Influenza B Viruses Possessing E119A and H274Y Neuraminidase Inhibitor Resistance-Associated Substitutions in Ferrets.

    Science.gov (United States)

    Pascua, Philippe Noriel Q; Marathe, Bindumadhav M; Burnham, Andrew J; Vogel, Peter; Webby, Richard J; Webster, Robert G; Govorkova, Elena A

    2016-01-01

    Neuraminidase (NA) inhibitors (NAIs) are the only antiviral drugs recommended for influenza treatment and prophylaxis. Although NAI-resistant influenza B viruses that could pose a threat to public health have been reported in the field, their fitness is poorly understood. We evaluated in ferrets the pathogenicity and relative fitness of reverse genetics (rg)-generated influenza B/Yamanashi/166/1998-like viruses containing E119A or H274Y NA substitutions (N2 numbering). Ferrets inoculated with NAI-susceptible rg-wild-type (rg-WT) or NAI-resistant (rg-E119A or rg-H274Y) viruses developed mild infections. Growth of rg-E119A virus in the nasal cavities was delayed, but the high titers at 3 days post-inoculation (dpi) were comparable to those of the rg-WT and rg-H274Y viruses (3.6-4.1 log10TCID50/mL). No virus persisted beyond 5 dpi and replication did not extend to the trachea or lungs. Positive virus antigen-staining of the nasal turbinate epithelium was intermittent with the rg-WT and rg-H274Y viruses; whereas antigen-staining for the rg-E119A virus was more diffuse. Virus populations in ferrets coinoculated with NAI-susceptible and -resistant viruses (1:1 mixture) remained heterogeneous at 5 dpi but were predominantly rg-WT (>70%). Although the E119A substitution was associated with delayed replication in ferrets, the H274Y substitution did not measurably affect viral growth properties. These data suggest that rg-H274Y has undiminished fitness in single virus inoculations, but neither rg-E119A nor rg-H274Y gained a fitness advantage over rg-WT in direct competition experiments without antiviral drug pressure. Taken together, our data suggest the following order of relative fitness in a ferret animal model: rg-WT > rg-H274Y > rg-E119A.

  11. Avian influenza H7N9/13 and H7N7/13: a comparative virulence study in chickens, pigeons, and ferrets.

    Science.gov (United States)

    Kalthoff, Donata; Bogs, Jessica; Grund, Christian; Tauscher, Kerstin; Teifke, Jens P; Starick, Elke; Harder, Timm; Beer, Martin

    2014-08-01

    Human influenza cases caused by a novel avian H7N9 virus in China emphasize the zoonotic potential of that subtype. We compared the infectivity and pathogenicity of the novel H7N9 virus with those of a recent European avian H7N7 strain in chickens, pigeons, and ferrets. Neither virus induced signs of disease despite substantial replication in inoculated chickens and rapid transmission to contact chickens. Evidence of the replication of both viruses in pigeons, albeit at lower levels of RNA excretion, was also detected. No clear-cut differences between the two H7 isolates emerged regarding replication and antibody development in avian hosts. In ferrets, in contrast, greater replication of the avian H7N9 virus than of the H7N7 strain was observed with significant differences in viral presence, e.g., in nasal wash, lung, and cerebellum samples. Importantly, both viruses showed the potential to spread to the mammal brain. We conclude that efficient asymptomatic viral replication and shedding, as shown in chickens, facilitate the spread of H7 viruses that may harbor zoonotic potential. Biosafety measures are required for the handling of poultry infected with avian influenza viruses of the H7 subtype, independently of their pathogenicity for gallinaceous poultry. This study is important to the field since it provides data about the behavior of the novel H7N9 avian influenza virus in chickens, pigeons, and ferrets in comparison with that of a recent low-pathogenicity H7N7 strain isolated from poultry. We clearly show that chickens, but not pigeons, are highly permissive hosts of both H7 viruses, allowing high-titer replication and virus shedding without any relevant clinical signs. In the ferret model, the potential of both viruses to infect mammals could be demonstrated, including infection of the brain. However, the replication efficiency of the H7N9 virus in ferrets was higher than that of the H7N7 strain. In conclusion, valuable data for the risk analysis of low

  12. Specific Features of the Hypothalamic Leptin Signaling Response to Cold Exposure Are Reflected in Peripheral Blood Mononuclear Cells in Rats and Ferrets

    Directory of Open Access Journals (Sweden)

    Bàrbara Reynés

    2017-08-01

    Full Text Available Objectives: Cold exposure induces hyperphagia to counteract fat loss related to lipid mobilization and thermogenic activation. The aim of this study was investigate on the molecular mechanisms involved in cold-induced compensatory hyperphagia.Methods: We analyzed the effect of cold exposure on gene expression of orexigenic and anorexigenic peptides, and of leptin signaling-related genes in the hypothalamus of rats at different ages (1, 2, 4, and 6 months, as well as in ferrets. We also evaluated the potential of peripheral blood mononuclear cells to reflect hypothalamic molecular responses.Results: As expected, cold exposure induced hypoleptinemia in rats, which could be responsible for the increased ratio of orexigenic/anorexigenic peptides gene expression in the hypothalamus, mainly due to decreased anorexigenic gene expression, especially in young animals. In ferrets, which resemble humans more closely, cold exposure induced greater changes in hypothalamic mRNA levels of orexigenic genes. Despite the key role of leptin in food intake control, the effect of cold exposure on the expression of key hypothalamic leptin signaling cascade genes is not clear. In our study, cold exposure seemed to affect leptin signaling in 4-month-old rats (increased Socs3 and Lepr expression, likely associated with the smaller-increase in food intake and decreased body weight observed at this particular age. Similarly, cold exposed ferrets showed greater hypothalamic Socs3 and Stat3 gene expression. Interestingly, peripheral blood mononuclear cells (PBMC mimicked the hypothalamic increase in Lepr and Socs3 observed in 4-month-old rats, and the increased Socs3 mRNA expression observed in ferrets in response to cold exposure.Conclusions: The most outstanding result of our study is that PBMC reflected the specific modulation of leptin signaling observed in both animal models, rats and ferrets, which points forwards PBMC as easily obtainable biological material to be

  13. The association between immunoglobulin concentrations and prediabetes prevalence in a large Chinese cohort.

    Science.gov (United States)

    Wang, Honglei; Song, Yanqi; Sun, Shaomei; Gao, Li; Liu, Li; Meng, Ge; Wu, Hongmei; Xia, Yang; Bao, Xue; Gu, Yeqing; Shi, Hongbin; Su, Qian; Fang, Liyun; Yang, Huijun; Wang, Xing; Zhou, Ming; Jia, Qiyu; Song, Kun; Zhang, Qing; Niu, Kaijun

    2017-08-01

    Prediabetes has received public attention owing to the increasing prevalence worldwide. Mounting evidence has indicated that inflammation directly contributed to the etiology of glucose metabolism disorders. Although immunoglobulins play a crucial role in immune responses, little research has been done on the link between immunoglobulins and prediabetes in adults. Hence, the aim of the present study was to explore the associations between immunoglobulins levels and prevalence of prediabetes in a general adult population. A cross-sectional study was conducted among 8856 adults (mean±standard deviation age: 48.4±10.7years) in Tianjin, China. The serum immunoglobulins concentrations were measured by the immunonephelometric technique. Prediabetes was diagnosed using the following parameters in accordance with the American Diabetes Association: fasting plasma glucose, postprandial glucose and glycosylated hemoglobin. The associations between concentrations of immunoglobulins and the prevalence of prediabetes were assessed using multiple logistic regression models. Overall, the prevalence of prediabetes was 37.4% (3311/8856). After controlling for confounders, compared with the lowest quintile, the odds ratios (95% confidence interval) of prediabetes for the highest quintile of immunoglobulins (immunoglobulin G, immunoglobulin E, immunoglobulin M and immunoglobulin A) were as follows: 1.06 (0.91-1.23), 1.31 (1.13-1.52), 0.86 (0.74-1.01), and 1.19 (1.03-1.38) (P for trend were 0.35, immunoglobulin E and immunoglobulin A levels were independently and positively associated with prediabetes prevalence. There was also a trending association between immunoglobulin M concentrations and prediabetes prevalence. Further studies are necessary to clarify if there is a causal association of immunoglobulins in prediabetes or if they reflect early immunologic disturbances in these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. A rapid, accurate and robust particle-based assay for the simultaneous screening of plasma samples for the presence of five different anti-cytokine autoantibodies

    DEFF Research Database (Denmark)

    Guldager, Daniel Kring Rasmussen; von Stemann, Jakob Hjorth; Larsen, Rune

    2015-01-01

    suitable for larger screenings. Based on confirmed antibody binding characteristics and the resultant reactivity in this multiplex assay, a classification of the c-aAb levels was suggested. The screening results of the recipients who received blood transfusions indicate that more studies are needed...... plasma samples and pooled normal immunoglobulin preparations were used to validate the assay. Plasma samples from 98 transfusion recipients, half of whom presented with febrile reactions, were tested by the assay. RESULTS: The assay detected specific and saturable immunoglobulin G (IgG) binding to each...... cytokine autoantibodies quantities in the negative plasma samples ranged between 80% and 125%. The analytical intra- and inter-assay variations were 4% and 11%, respectively. Varying c-aAb levels were detectable in the transfusion recipients. There was no difference in c-aAb frequency between the patients...

  15. Single- and multiple-clade influenza A H5N1 vaccines induce cross protection in ferrets.

    Science.gov (United States)

    Forrest, Heather L; Khalenkov, Alexey M; Govorkova, Elena A; Kim, Jeong-Ki; Del Giudice, Giuseppe; Webster, Robert G

    2009-06-24

    The rapid evolution, genetic diversity, broad host range, and increasing human infection with avian influenza A (H5N1) viruses highlight the need for an efficacious cross-clade vaccine. Using the ferret model, we compared induction of cross-reactive immunity and protective efficacy of three single-clade H5N1 vaccines and a novel multiple-clade H5N1 vaccine, with and without MF59 adjuvant. Reverse genetics (rg) was used to generate vaccine viruses containing the hemagglutinin (HA) and neuraminidase genes of wild-type H5N1 viruses. Ferrets received two doses of inactivated whole-virus vaccine separated by 3 weeks. Single-clade vaccines (7.5 microg HA per dose) included rg-A/Vietnam/1203/04 (clade 1), rg-A/Hong Kong/213/03 (clade 1), and rg-A/Japanese White Eye/Hong Kong/1038/06 (clade 2.3). The multiple-clade vaccine contained 3.75 microg HA per dose of each single-clade vaccine and of rg-A/Whooper Swan/Mongolia/244/05 (clade 2.2). Two doses of vaccine were required to substantially increase anti-HA and virus neutralizing antibody titers to H5N1 viruses. MF59 adjuvant enhanced induction of clade-specific and cross-clade serum antibody responses, reduced frequency of infection (as determined by upper respiratory tract virus shedding and seroconversion data), and eliminated disease signs. The rg-A/Hong Kong/213/03 vaccine induced the highest antibody titers to homologous and heterologous H5N1 viruses, while rg-A/Japanese White Eye/Hong Kong/1038/06 vaccine induced the lowest. The multiple-clade vaccine was broadly immunogenic against clade 1 and 2 viruses. The rg-A/Vietnam/1203/04 vaccine (the currently stockpiled H5N1 vaccine) most effectively reduced upper respiratory tract virus shedding after challenge with clade 1 and 2 viruses. Importantly, all vaccines protected against lethal challenge with A/Vietnam/1203/04 virus and provided cross-clade protection.

  16. Oral Serum-Derived Bovine Immunoglobulin/Protein Isolate Has Immunomodulatory Effects on the Colon of Mice that Spontaneously Develop Colitis.

    Science.gov (United States)

    Pérez-Bosque, Anna; Miró, Lluïsa; Maijó, Mònica; Polo, Javier; Campbell, Joy M; Russell, Louis; Crenshaw, Joe D; Weaver, Eric; Moretó, Miquel

    2016-01-01

    Dietary immunoglobulin concentrates prepared from animal plasma can modulate the immune response of gut-associated lymphoid tissue (GALT). Previous studies have revealed that supplementation with serum-derived bovine immunoglobulin/protein isolate (SBI) ameliorates colonic barrier alterations in the mdr1a-/- genetic mouse model of IBD. Here, we examine the effects of SBI on mucosal inflammation in mdr1a-/- mice that spontaneously develop colitis. Wild type (WT) mice and mice lacking the mdr1a gene (KO) were fed diets supplemented with either SBI (2% w/w) or milk proteins (Control diet), from day 21 (weaning) until day 56. Leucocytes in mesenteric lymph nodes (MLN) and in lamina propria were determined, as was mucosal cytokine production. Neutrophil recruitment and activation in MLN and lamina propria of KO mice were increased, but were significantly reduced in both by SBI supplementation (p stress (p < 0.05) and SBI supplementation reduced this variable (p < 0.05). The Tact/Treg lymphocyte ratios in MLN and lamina propria were also increased in KO animals, but SBI prevented these changes (both p < 0.05). In the colon of KO mice, there was an increased production of mucosal pro-inflammatory cytokines such as IL-2 (2-fold), IL-6 (26-fold) and IL-17 (19-fold), and of chemokines MIP-1β (4.5-fold) and MCP-1 (7.2-fold). These effects were significantly prevented by SBI (p < 0.05). SBI also significantly increased TGF-β secretion in the colon mucosa, suggesting a role of this anti-inflammatory cytokine in the modulation of GALT and the reduction of the severity of the inflammatory response during the onset of colitis.

  17. Oral Serum-Derived Bovine Immunoglobulin/Protein Isolate Has Immunomodulatory Effects on the Colon of Mice that Spontaneously Develop Colitis.

    Directory of Open Access Journals (Sweden)

    Anna Pérez-Bosque

    Full Text Available Dietary immunoglobulin concentrates prepared from animal plasma can modulate the immune response of gut-associated lymphoid tissue (GALT. Previous studies have revealed that supplementation with serum-derived bovine immunoglobulin/protein isolate (SBI ameliorates colonic barrier alterations in the mdr1a-/- genetic mouse model of IBD. Here, we examine the effects of SBI on mucosal inflammation in mdr1a-/- mice that spontaneously develop colitis. Wild type (WT mice and mice lacking the mdr1a gene (KO were fed diets supplemented with either SBI (2% w/w or milk proteins (Control diet, from day 21 (weaning until day 56. Leucocytes in mesenteric lymph nodes (MLN and in lamina propria were determined, as was mucosal cytokine production. Neutrophil recruitment and activation in MLN and lamina propria of KO mice were increased, but were significantly reduced in both by SBI supplementation (p < 0.05. The increased neutrophil recruitment and activation observed in KO mice correlated with increased colon oxidative stress (p < 0.05 and SBI supplementation reduced this variable (p < 0.05. The Tact/Treg lymphocyte ratios in MLN and lamina propria were also increased in KO animals, but SBI prevented these changes (both p < 0.05. In the colon of KO mice, there was an increased production of mucosal pro-inflammatory cytokines such as IL-2 (2-fold, IL-6 (26-fold and IL-17 (19-fold, and of chemokines MIP-1β (4.5-fold and MCP-1 (7.2-fold. These effects were significantly prevented by SBI (p < 0.05. SBI also significantly increased TGF-β secretion in the colon mucosa, suggesting a role of this anti-inflammatory cytokine in the modulation of GALT and the reduction of the severity of the inflammatory response during the onset of colitis.

  18. Eosinophil secretion of granule-derived cytokines

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    Lisa A Spencer

    2014-10-01

    Full Text Available Eosinophils are tissue-dwelling leukocytes, present in the thymus, and gastrointestinal and genitourinary tracts of healthy individuals at baseline, and recruited, often in large numbers, to allergic inflammatory foci and sites of active tissue repair. The biological significance of eosinophils is vast and varied. In health, eosinophils support uterine and mammary gland development, and maintain bone marrow plasma cells and adipose tissue alternatively activated macrophages, while in response to tissue insult eosinophils function as inflammatory effector cells, and, in the wake of an inflammatory response, promote tissue regeneration and wound healing. One common mechanism driving many of the diverse eosinophil functions is the regulated and differential secretion of a vast array of eosinophil-derived cytokines. Eosinophils are distinguished from most other leukocytes in that many, if not all, of the over three dozen eosinophil-derived cytokines are pre-synthesized and stored within intracellular granules, poised for very rapid, stimulus-induced secretion. Eosinophils engaged in cytokine secretion in situ utilize distinct pathways of cytokine release that include: classical exocytosis, whereby granules themselves fuse with the plasma membrane and release their entire contents extracellularly; piecemeal degranulation, whereby granule-derived cytokines are selectively mobilized into vesicles that emerge from granules, traverse the cytoplasm and fuse with the plasma membrane to release discrete packets of cytokines; and eosinophil cytolysis, whereby intact granules are extruded from eosinophils, and deposited within tissues. In this latter scenario, extracellular granules can themselves function as stimulus-responsive secretory-competent organelles within the tissue. Here we review the distinctive processes of differential secretion of eosinophil granule-derived cytokines.

  19. Immunoglobulins: Benefits and risks from the patient's point of view.

    Science.gov (United States)

    Revol, Bruno; Bickert, Laura; Sarrot-Reynauld, Françoise; Allenet, Benoit

    2017-12-01

    Patients have to be informed about the risks and benefits of medicinal products derived from human plasma. No study has examined the patient's perspective yet. Our objective was to assess perceived benefits and risks of immunoglobulins administration from the patient's point of view. Thirty-four patients receiving subcutaneous or intravenous immunoglobulins for chronic disorders at a single university hospital were asked to complete a survey. Although the level of comfort was high, the results revealed variable and incomplete knowledge, in particular about the nature of the treatment. Greater efforts should be made by health professionals to provide information to patients about plasma-derived medicinal products. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  20. Intravenous immunoglobulin treatment in therapy-resistant epidermolysis bullosa acquisita.

    Science.gov (United States)

    Kofler, H; Wambacher-Gasser, B; Topar, G; Weinlich, G; Schuler, G; Hintner, H; Romani, N; Fritsch, P

    1997-02-01

    Epidermolysis bullosa acquisita is an uncommon autoimmune bullous disease of the skin and mucous membranes. It is chronic, disabling, and difficult to treat. We describe a case of severe epidermolysis bullosa acquisita of 7 years' duration that had been treated with azathioprine, corticosteroids, chlorambucil, plasma exchanges, cyclophosphamide, cyclosporine, and colchicine without any lasting effect. Seven cycles of treatment were administered with immunoglobulin given intravenously at a low dose, 40 mg/kg body weight daily for 5 days. The patient was free of disease for 10 months after the initiation of therapy. We suggest that low-dose regimens of immunoglobulins may be as effective in this disease as the high-dose regimens suggested in the literature, and at much lower cost.

  1. A role for PCNA ubiquitination in immunoglobulin hypermutation.

    Directory of Open Access Journals (Sweden)

    Hiroshi Arakawa

    2006-11-01

    Full Text Available Proliferating cell nuclear antigen (PCNA is a DNA polymerase cofactor and regulator of replication-linked functions. Upon DNA damage, yeast and vertebrate PCNA is modified at the conserved lysine K164 by ubiquitin, which mediates error-prone replication across lesions via translesion polymerases. We investigated the role of PCNA ubiquitination in variants of the DT40 B cell line that are mutant in K164 of PCNA or in Rad18, which is involved in PCNA ubiquitination. Remarkably, the PCNA(K164R mutation not only renders cells sensitive to DNA-damaging agents, but also strongly reduces activation induced deaminase-dependent single-nucleotide substitutions in the immunoglobulin light-chain locus. This is the first evidence, to our knowledge, that vertebrates exploit the PCNA-ubiquitin pathway for immunoglobulin hypermutation, most likely through the recruitment of error-prone DNA polymerases.

  2. A database of immunoglobulins with integrated tools: DIGIT.

    KAUST Repository

    Chailyan, Anna

    2011-11-10

    The DIGIT (Database of ImmunoGlobulins with Integrated Tools) database (http://biocomputing.it/digit) is an integrated resource storing sequences of annotated immunoglobulin variable domains and enriched with tools for searching and analyzing them. The annotations in the database include information on the type of antigen, the respective germline sequences and on pairing information between light and heavy chains. Other annotations, such as the identification of the complementarity determining regions, assignment of their structural class and identification of mutations with respect to the germline, are computed on the fly and can also be obtained for user-submitted sequences. The system allows customized BLAST searches and automatic building of 3D models of the domains to be performed.

  3. [Intravenous immunoglobulin therapy for kidney diseases in children].

    Science.gov (United States)

    Zwolińska, Danuta

    2011-06-01

    Intravenous immunoglobulin (IVIG) for the treatment of primary immunodeficiency disorders have been administrated for more than 25 years. However, the recognition of the anti-inflammatory and immune-modulatory actions of IVIG resulted broader applications to autoimmunity and systemic inflammatory conditions. The major focus of this review is the usefulness of IVIG therapy in children kidney disease, particularly in severe, atypical hemolytic-uremic syndrome and thrombotic thrombocytopenic purpura, refractory to standard therapy, including plasmaferesis. The role of intravenous immunoglobulins in the treatment and prevention of infection, the most common complication in nephrotic syndrome is also discussed. Probably, in the future, similarly to adults, IVIG will be used for the therapy of some forms of glomerulopathies.

  4. Effect of fluoride on salivary immunoglobulins and sialic acid

    Directory of Open Access Journals (Sweden)

    Kadriye Görkem Ulu Güzel

    Full Text Available Summary Objective: The aim of our study was to evaluate the effect of fluoride on salivary immunoglobulin and sialic acid levels in children with dental fluorosis and healthy teeth who live in places with high fluoride concentration in drinking water. Method: Fifty-one (51 healthy children between 6 and 12 years old with no caries were randomly selected from primary schools enrolled in the dental-care program operated by the Department of Pediatric Dentistry. The children were divided into two groups: group I comprised 26 children with dental fluorosis [Thylstrup-Fejerskov Dental Fluorosis Index (TFI = 4] who lived in Isparta (2.7-2.8 ppm, and group II consisted of 25 children without dental fluorosis who were born in low-fluoride areas and had lived in Isparta for only the previous two years. Stimulated and unstimulated saliva were collected and analyzed for fluoride, salivary immunoglobulins and sialic acid levels. Results: Sialic acid level was correlated negatively with age. Levels of secretory immunoglobulin A (sIgA and secretory immunoglobulin G (sIgG were higher in children with dental fluorosis compared with those in group II, although these differences were not significant. Conclusion: Increased sIgA and sIgG levels may arrest the progression of caries in subjects with dental fluorosis. Given the risks of dental fluorosis, further studies of the effects of different fluoride levels in drinking water on salivary composition of children with mixed dentition are needed to confirm the results of our study and to provide data for comparison.

  5. Serologic activity of G immunoglobulin of irradiated rabbits

    International Nuclear Information System (INIS)

    Ivanov, A.A.; Nevinnaya, A.P.; Mozhajskij, A.M.; Snisar', N.A.

    1977-01-01

    Serologic immunochemical properties of immunoglobulins G (IgG) isolated from blood serum of normal rabbits and those given lethal and midlethal doses of radiation have been comparatively studied. A marked increase in the IgG level was detected in the recovery period of radiation sickness. The number of complement-binding antitissue antibodies in IgG grew in that period, and the anticomplementary activity and the catabolism rate of IgG increased in normal organism

  6. Immunoglobulin G4-related disease: autoimmune pancreatitis and extrapancreatic manifestations

    Directory of Open Access Journals (Sweden)

    Daniel Alvarenga Fernandes

    2016-04-01

    Full Text Available Abstract We present a case of immunoglobulin G4 (IgG4-related disease with pancreatic and extrapancreatic involvement, including the biliary and renal systems. Given the importance of imaging methods for the diagnosis of IgG4-related disease and its differentiation from pancreatic adenocarcinoma, we emphasize important abdominal computed tomography and magnetic resonance imaging findings related to this recently recognized systemic autoimmune disease.

  7. An immunoglobulin E assay using radiolabelled Fab' and ammonium sulfate

    International Nuclear Information System (INIS)

    Wilcsek, R.J.; Hamburger, R.N.

    1978-01-01

    An immunochemical assay is described in which a radiolabelled antibody fragment, Fab', is bound specifically to immunoglobulin E (IgE), and precipitated with ammonium sulfate. The radioactivity in the precipitate is a measure of the amount of IgE in the sample. Results for six serum samples are compared using the double antibody and ammonium sulfate methods as well as the papωr radioimmunosorbent test (PRIST)

  8. Immunoglobulin concentration in tears of contact lens wearers.

    Science.gov (United States)

    Maurya, Rajendra P; Bhushan, Prashant; Singh, Virendra P; Singh, Mahendra K; Kumar, Prakash; Bhatia, Ravindra P S; Singh, Usha

    2014-01-01

    To evaluate changes in the concentration of tear immunoglobulins in contact lens wearers. A total of 45 cases including 23 contact lens wearers (43 eyes) and 22 age and sex matched healthy controls having no ocular pathology were studied for immunoglobulins (IgA, IgG, IgM) in their tears by single radial immunodiffusion method. Most of the cases used soft (56.6%) and semi-soft gas permeable (30.4%) contact lenses. Tear IgM was detected in only 17.4% and tear IgG in 43.6% of contact lens wearers, while in controls IgG was detected in 9.1% but none of the controls had IgM. There was a significant rise in total tear IgA (13.17 ± 4.44 mg/dl) in contact lens wearer as compared to controls (8.93 ± 3.79 mg/dl). Rise of tear IgA was more in symptomatic patients (15.38 ± 5.28 mg/dl) and in those wearing hard (19.73 ± 5.43 mg/dl) and semi-soft contact lenses (13.31 ± 5.43 mg/dl). A significant increase in tear IgA was noticed in subjects wearing lenses for >3 years (15.69 ± 5.39 mg/dl). About 43.4% of lens wearers were symptomatic and 80% of their lenses showed deposits and/or haziness. All cases with IgM in tear were symptomatic. The relation of immunoglobulin concentration with increasing duration of wear and material of contact lens shows that tear immunoglobulin rise accrues due to mechanical stimulation, hence contact lenses should not be used for a long period and lenses of hard nature should be discouraged. The maintenance, cleaning and deproteinization of the lenses are of high importance to avoid immunostimulation.

  9. Diversity Analysis of the Immunoglobulin M Heavy Chain Gene in ...

    African Journals Online (AJOL)

    A full-length cDNA encoding the immunoglobulin (IgM) heavy chain gene of Nile tilapia was successfully cloned using the 5' and 3' RACE techniques. The complete cDNA of the Nile tilapia IgM heavy chain gene is 1,921 bp in length and has an open reading frame (ORF) of 1,740 bp, which corresponds to 580 amino acid ...

  10. A Case of Immunoglobulin E Mediated Anaphylaxis to Levodropropizine

    OpenAIRE

    Park, Kyung Hee; Yun, Il Seon; Choi, Soo-Young; Lee, Jae-Hyun; Hong, Chein-Soo; Park, Jung-Won

    2012-01-01

    We experienced a case of immunoglobulin E (IgE) mediated anaphylaxis to levodropropizine. The patient was an 18-year old Korean woman. After taking the common cold medication including acetaminophen, domperidone, and levodropropizine, skin rash, angioedema and anaphylaxis were developed immediately. As she was tolerable to acetaminophen alone, we thought the culprit agent was maybe a levodropropizine tablet. To confirm the culprit, she underwent skin prick test and oral drug provocation test ...

  11. Immunoglobulin M-enriched intravenous polyclonal immunoglobulins reduce bacteremia following Klebsiella pneumoniae infection in an acute respiratory distress syndrome rat model

    NARCIS (Netherlands)

    Lachmann, R. A.; van Kaam, A. H. L. C.; Haitsma, J. J.; Verbrugge, S. J. C.; Delreu, F.; Lachmann, B.

    2004-01-01

    Mechanical ventilation is known to induce bacterial translocation from the lung into the systemic circulation. This study determined the effect of immunoglobulin M (IgM)-enriched polyclonal immunoglobulins on bacteremia due to ventilation-induced translocation in an acute respiratory distress

  12. Comprehensive N-Glycan Profiling of Avian Immunoglobulin Y

    Science.gov (United States)

    Millán Martín, Silvia; Wormald, Mark R.; Zapatero-Rodríguez, Julia; Conroy, Paul J.; O’Kennedy, Richard J.; Rudd, Pauline M.; Saldova, Radka

    2016-01-01

    Recent exploitation of the avian immune system has highlighted its suitability for the generation of high-quality, high-affinity antibodies to a wide range of antigens for a number of therapeutic and biotechnological applications. The glycosylation profile of potential immunoglobulin therapeutics is species specific and is heavily influenced by the cell-line/culture conditions used for production. Hence, knowledge of the carbohydrate moieties present on immunoglobulins is essential as certain glycan structures can adversely impact their physicochemical and biological properties. This study describes the detailed N-glycan profile of IgY polyclonal antibodies from the serum of leghorn chickens using a fully quantitative high-throughput N-glycan analysis approach, based on ultra-performance liquid chromatography (UPLC) separation of released glycans. Structural assignments revealed serum IgY to contain complex bi-, tri- and tetra-antennary glycans with or without core fucose and bisects, hybrid and high mannose glycans. High sialic acid content was also observed, with the presence of rare sialic acid structures, likely polysialic acids. It is concluded that IgY is heavily decorated with complex glycans; however, no known non-human or immunogenic glycans were identified. Thus, IgY is a potentially promising candidate for immunoglobulin-based therapies for the treatment of various infectious diseases. PMID:27459092

  13. Endogenous immunoglobulins and sepsis: New perspectives for guiding replacement therapies.

    Science.gov (United States)

    Bermejo-Martin, Jesús F; Giamarellos-Bourboulis, Evangelos J

    2015-12-01

    The recently emerging concept of immunosuppression developing in the field of severe sepsis generated the need to measure circulating immunoglobulins as part of the necessary tests to evaluate immunocompetence status in patients suffering from this condition. Serum concentrations can be used as a surrogate marker of the final outcome and as a biomarker to explore the need for supplementation of the host with intravenous immunoglobulin preparations. Available evidence from recent clinical studies pinpoints the main observations. The first is that circulating IgM is a phenomenon associated with progression from severe sepsis to septic shock. Deficient kinetics of circulating IgM during the first 7 days following the start of vasopressors is linked with unfavourable outcome. The second is the development of immunoscores using low levels of IgM, IgG1 and IgA. These immunoscores can predict 28-day mortality with an odds ratio ranging between 3 and 5. Novel techniques for evaluating patient's immune status are shedding new light on the development of modern therapeutics where immunoglobulin replacement may be part of a personalised therapeutic approach. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Regulation of human cytokines by Cordyceps militaris.

    Science.gov (United States)

    Sun, Yong; Shao, Yani; Zhang, Zhiguo; Wang, Lianfen; Mariga, Alfred M; Pang, Guangchang; Geng, Chaoyu; Ho, Chi-Tang; Hu, Qiuhui; Zhao, Liyan

    2014-12-01

    Cordyceps (Cordyceps militaris) exhibits many biological activities including antioxidant, inhibition of inflammation, cancer prevention, hypoglycemic, and antiaging properties, etc. However, a majority of studies involving C. militaris have focused only on in vitro and animal models, and there is a lack of direct translation and application of study results to clinical practice (e.g., health benefits). In this study, we investigated the regulatory effects of C. militaris micron powder (3 doses) on the human immune system. The study results showed that administration of C. militaris at various dosages reduced the activity of cytokines such as eotaxin, fibroblast growth factor-2, GRO, and monocyte chemoattractant protein-1. In addition, there was a significant decrease in the activity of various cytokines, including GRO, sCD40L, and tumor necrosis factor-α, and a significant downregulation of interleukin-12(p70), interferon-γ inducible protein 10, and macrophage inflammatory protein-1β activities, indicating that C. militaris at all three dosages downregulated the activity of cytokines, especially inflammatory cytokines and chemokines. Different dosages of C. militaris produced different changes in cytokines. Copyright © 2014. Published by Elsevier B.V.

  15. Regulation of human cytokines by Cordyceps militaris

    Directory of Open Access Journals (Sweden)

    Yong Sun

    2014-12-01

    Full Text Available Cordyceps (Cordyceps militaris exhibits many biological activities including antioxidant, inhibition of inflammation, cancer prevention, hypoglycemic, and antiaging properties, etc. However, a majority of studies involving C. militaris have focused only on in vitro and animal models, and there is a lack of direct translation and application of study results to clinical practice (e.g., health benefits. In this study, we investigated the regulatory effects of C. militaris micron powder (3 doses on the human immune system. The study results showed that administration of C. militaris at various dosages reduced the activity of cytokines such as eotaxin, fibroblast growth factor-2, GRO, and monocyte chemoattractant protein-1. In addition, there was a significant decrease in the activity of various cytokines, including GRO, sCD40L, and tumor necrosis factor-α, and a significant downregulation of interleukin-12(p70, interferon-γ inducible protein 10, and macrophage inflammatory protein-1β activities, indicating that C. militaris at all three dosages downregulated the activity of cytokines, especially inflammatory cytokines and chemokines. Different dosages of C. militaris produced different changes in cytokines.

  16. Evaluation of Serum Cytokines Levels and the Role of Cannabidiol Treatment in Animal Model of Asthma

    Directory of Open Access Journals (Sweden)

    Francieli Vuolo

    2015-01-01

    Full Text Available Asthma represents a public health problem and traditionally is classified as an atopic disease, where the allergen can induce clinical airway inflammation, bronchial hyperresponsiveness, and reversible obstruction of airways. Studies have demonstrated the presence of T-helper 2 lymphocytes in the lung of patients with asthma. These cells are involved in cytokine production that regulates immunoglobulin synthesis. Recognizing that T cell interaction with antigens/allergens is key to the development of inflammatory diseases, the aim of this study is to evaluate the anti-inflammatory potential of cannabidiol (CBD in this setting. Asthma was induced in 8-week-old Wistar rats by ovalbumin (OVA. In the last 2 days of OVA challenge animals received CBD (5 mg/kg, i.p. and were killed 24 hours after. The levels of IL-4, IL-5, IL-13, IL-6, IL-10, and TNF-α were determinate in the serum. CBD treatment was able to decrease the serum levels of all analyzed cytokines except for IL-10 levels. CBD seems to be a potential new drug to modulate inflammatory response in asthma.

  17. Evaluation of Serum Cytokines Levels and the Role of Cannabidiol Treatment in Animal Model of Asthma

    Science.gov (United States)

    Vuolo, Francieli; Petronilho, Fabricia; Sonai, Beatriz; Ritter, Cristiane; Hallak, Jaime E. C.; Zuardi, Antonio Waldo; Crippa, José A.; Dal-Pizzol, Felipe

    2015-01-01

    Asthma represents a public health problem and traditionally is classified as an atopic disease, where the allergen can induce clinical airway inflammation, bronchial hyperresponsiveness, and reversible obstruction of airways. Studies have demonstrated the presence of T-helper 2 lymphocytes in the lung of patients with asthma. These cells are involved in cytokine production that regulates immunoglobulin synthesis. Recognizing that T cell interaction with antigens/allergens is key to the development of inflammatory diseases, the aim of this study is to evaluate the anti-inflammatory potential of cannabidiol (CBD) in this setting. Asthma was induced in 8-week-old Wistar rats by ovalbumin (OVA). In the last 2 days of OVA challenge animals received CBD (5 mg/kg, i.p.) and were killed 24 hours after. The levels of IL-4, IL-5, IL-13, IL-6, IL-10, and TNF-α were determinate in the serum. CBD treatment was able to decrease the serum levels of all analyzed cytokines except for IL-10 levels. CBD seems to be a potential new drug to modulate inflammatory response in asthma. PMID:26101464

  18. Oral Administration of p-Hydroxycinnamic Acid Attenuates Atopic Dermatitis by Downregulating Th1 and Th2 Cytokine Production and Keratinocyte Activation.

    Directory of Open Access Journals (Sweden)

    Hyun-Su Lee

    Full Text Available Atopic dermatitis (AD is a complex disease that is caused by various factors, including environmental change, genetic defects, and immune imbalance. We previously showed that p-hydroxycinnamic acid (HCA isolated from the roots of Curcuma longa inhibits T-cell activation without inducing cell death. Here, we demonstrated that oral administration of HCA in a mouse model of ear AD attenuates the following local and systemic AD manifestations: ear thickening, immune-cell infiltration, production of AD-promoting immunoregulatory cytokines in ear tissues, increased spleen and draining lymph node size and weight, increased pro-inflammatory cytokine production by draining lymph nodes, and elevated serum immunoglobulin production. HCA treatment of CD4+ T cells in vitro suppressed their proliferation and differentiation into Th1 or Th2 and their Th1 and Th2 cytokine production. HCA treatment of keratinocytes lowered their production of the pro-inflammatory cytokines that drive either Th1 or Th2 responses in AD. Thus, HCA may be of therapeutic potential for AD as it acts by suppressing keratinocyte activation and downregulating T-cell differentiation and cytokine production.

  19. A universal influenza virus vaccine candidate confers protection against pandemic H1N1 infection in preclinical ferret studies.

    Science.gov (United States)

    Nachbagauer, Raffael; Liu, Wen-Chun; Choi, Angela; Wohlbold, Teddy John; Atlas, Talia; Rajendran, Madhusudan; Solórzano, Alicia; Berlanda-Scorza, Francesco; García-Sastre, Adolfo; Palese, Peter; Albrecht, Randy A; Krammer, Florian

    2017-01-01

    Influenza viruses evade human adaptive immune responses due to continuing antigenic changes. This makes it necessary to re-formulate and re-administer current seasonal influenza vaccines on an annual basis. Our pan-influenza vaccination approach attempts to redirect antibody responses from the variable, immuno-dominant hemagglutinin head towards the conserved-but immuno-subdominant-hemagglutinin stalk. The strategy utilizes sequential immunization with chimeric hemagglutinin-based vaccines expressing exotic head domains, and a conserved hemagglutinin stalk. We compared a live-attenuated influenza virus prime followed by an inactivated split-virus boost to two doses of split-virus vaccines and assessed the impact of adjuvant on protection against challenge with pandemic H1N1 virus in ferrets. All tested immunization regimens successfully induced broadly cross-reactive antibody responses. The combined live-attenuated/split virus vaccination conferred superior protection against pandemic H1N1 infection compared to two doses of split-virus vaccination. Our data support advancement of this chimeric hemagglutinin-based vaccine approach to clinical trials in humans.

  20. Enkephalinase inhibitors potentiate tackykinin-induced release of /sup 35/SO/sub 4/-labeled macromolecules from ferret trachea

    Energy Technology Data Exchange (ETDEWEB)

    Borson, D.B.; Gold, M.; Varsano, S.; Caughey, G.; Ramachandran, J.; Nadel, J.A.

    1986-03-01

    To study the roles of tachykinins and endogenous proteinases in regulating secretion from ferret tracheal glands, the authors measured the release of /sup 35/SO/sub 4/-labeled macromolecules after incubating segments of trachea in Ussing chambers in the presence of /sup 35/SO/sub 4/. 85% of the total macromolecular radioactivity was in fractions of molecular weights greater than or equal to 10/sup 6/. The response to substance P (SP) was concentration-dependent, with a threshold of 10/sup -9/ M, and responses to 10/sup -6/M and 10/sup -5/M of 87 +/- 9 and 156 +/- 26 pmol/cm/sup 2//h, respectively (n = 6 ea). The enkephalinase inhibitor, thiorphan, increased the secretory response to SP (10/sup -6/M) in a concentration-dependent fashion, with a threshold of 10/sup -8/M, and a response to SP after 10/sup -4/M thiorphan of 268 +/- 58 pmol/cm/sup 2//h (p < 0.05; n = 6). Phosphoramidon also increased SP-induced secretion to 334 +/- 69 pmol/cm/sup 2//h (p < 0.005; n = 4), and also potentiated the secretory responses to neurokinins A and B, physalaemin, eledoisin, and kassinin, but did not potentiate the secretory responses to either bradykinin or vasoactive intestinal peptide. Other proteinase inhibitors did not potentiate SP-induced secretion. These results suggest that enkephalinase in the airway degrades tachykinins, and may therefore play a role in regulating tachykinin-induced effects.

  1. Contact transmission of influenza virus between ferrets imposes a looser bottleneck than respiratory droplet transmission allowing propagation of antiviral resistance

    Science.gov (United States)

    Frise, Rebecca; Bradley, Konrad; van Doremalen, Neeltje; Galiano, Monica; Elderfield, Ruth A.; Stilwell, Peter; Ashcroft, Jonathan W.; Fernandez-Alonso, Mirian; Miah, Shahjahan; Lackenby, Angie; Roberts, Kim L.; Donnelly, Christl A.; Barclay, Wendy S.

    2016-01-01

    Influenza viruses cause annual seasonal epidemics and occasional pandemics. It is important to elucidate the stringency of bottlenecks during transmission to shed light on mechanisms that underlie the evolution and propagation of antigenic drift, host range switching or drug resistance. The virus spreads between people by different routes, including through the air in droplets and aerosols, and by direct contact. By housing ferrets under different conditions, it is possible to mimic various routes of transmission. Here, we inoculated donor animals with a mixture of two viruses whose genomes differed by one or two reverse engineered synonymous mutations, and measured the transmission of the mixture to exposed sentinel animals. Transmission through the air imposed a tight bottleneck since most recipient animals became infected by only one virus. In contrast, a direct contact transmission chain propagated a mixture of viruses suggesting the dose transferred by this route was higher. From animals with a mixed infection of viruses that were resistant and sensitive to the antiviral drug oseltamivir, resistance was propagated through contact transmission but not by air. These data imply that transmission events with a looser bottleneck can propagate minority variants and may be an important route for influenza evolution. PMID:27430528

  2. The claustrum of the ferret: afferent and efferent connections to lower and higher order visual cortical areas.

    Directory of Open Access Journals (Sweden)

    Nina ePatzke

    2014-02-01

    Full Text Available The claustrum, a subcortical telencephalic structure, is known to be reciprocally interconnected to almost all cortical regions; however, a systematic analysis of claustrocortical connectivity with physiologicall identified lower and higher order visual cortical areas has not been undertaken. In the current study we used biotinylated dextran amine to trace the connections of the ferret claustrum with lower (occipital areas 17, 18, 19 and 21 and higher (parietal and temporal areas PPc, PPr, 20a, 20b, AEV order visual cortical areas. No connections between the claustrum and area 17 were observed. Occipital visual areas 18, 19 and 21 revealed a reciprocal connectivity mainly to the caudal part of the claustrum. After injection into parietal areas PPc and PPr labelled neurons and terminals were found throughout almost the entire anterocaudal extent of the dorsal claustrum. Area 20b revealed reciprocal connections mainly to the caudal-ventral claustrum, although some labelled neurons and terminals were observed in the dorso-central claustrum. No projection from the claustrum to areas AEV and 20a could be observed, though projections from AEV and 20a to the claustrum were found. Only injections placed in areas PPr and AEV resulted in anterogradely labelled terminals in the contralateral claustrum. Our results suggest that lower order visual areas have clearly defined connectivity zones located in the caudal claustrum, whereas higher order visual areas, even if not sending and/or receiving projections from the entire claustrum, show a more widespread connectivity.

  3. Ferret: an open-source code for simulating thermodynamical evolution and phase transformations in complex materials systems at mesoscale

    Science.gov (United States)

    Nakhmanson, Serge; Mangeri, John; Pitike, Krishna; Kuna, Lukasz; Jokisaari, Andrea; Alpay, S. Pamir; Heinonen, Olle

    Ferret is an open-source real-space finite-element-method (FEM) based code for simulating behavior of materials systems with coupled physical properties at mesoscale. It is built on MOOSE, Multiphysics Object Oriented Simulation Environment, and is being developed by the UConn-ANL collaboration. Here we provide an overview of computational approach utilized by the code, as well as its technical features and the associated software within our computational tool chain. We also highlight a variety of code application examples that are being pursued in collaboration with a number of different experimental groups. These applications include (a) evaluations of size- and microstructure-dependent elastic and optical properties of core-shell nanoparticles, including Zn/ZnO and ZnO/TiO2 core/shell material combinations; (b) modeling of the influence of shape, size and elastic distortions of monolithic ZnO and Zn/ZnO core/shell nanowires on their optical properties; (c) studies of the properties and domain-wall dynamics in perovskite-ferroelectric films, nanowires and nanoridges, and (d) investigation of topological phases and size effects in ferroelectric nanoparticles embedded in a dielectic matrix.

  4. Two classes of ouabain binding sites in ferret heart and two forms of Na+-K+-ATPase

    Energy Technology Data Exchange (ETDEWEB)

    Ng, Y.C.; Akera, T.

    1987-05-01

    In partially purified Na+-K+-adenosinetriphosphatase (ATPase) obtained from ferret heart, ouabain produced a monophasic inhibition curve; however, the curve spanned over 5 logarithmic units, indicating the presence of more than one classes of enzyme. (/sup 3/H)ouabain binding studies revealed high-and low-affinity binding sites in approximately equal abundance, with apparent dissociation constants of 10 and 230 nM, respectively. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of phosphoenzyme formed from (gamma-/sup 32/P)ATP showed two distinct K+-sensitive bands of approximately 100,000 molecular weight. Phosphoenzyme formation from the high-molecular-weight alpha(+) form was selectively inhibited by N-ethylmaleimide. Ouabain caused a 50% inhibition of phosphorylation of the alpha(+) form at 40 nM and the lower-molecular-weight alpha form at 300 nM. In papillary muscle preparations, 1-30 nM ouabain produced a modest positive inotropic effect that reached an apparent plateau at 30 nM. Further increases in ouabain concentrations, however, produced additional and prominent inotropic effects at 0.1-10 microM. These results indicate for the first time in cardiac muscle that the high- and low-affinity ouabain binding sites are associated with the alpha(+) and alpha forms of the Na+-K+-ATPase, respectively, and that binding of ouabain to either of these sites causes enzyme inhibition and the positive inotropic effect.

  5. The role of cytokines in postmenopausal osteoporosis.

    Science.gov (United States)

    Brincat, S D; Borg, M; Camilleri, G; Calleja-Agius, J

    2014-08-01

    Postmenopausal osteoporosis is a silent systemic progressive disease characterised by a decrease in bone mass per unit volume. This condition compromises the physical strength of the skeleton and increases the susceptibility to fractures on minor trauma. The imbalance between bone formation and bone resorption is known to be responsible for postmenopausal bone loss. Estrogen deficiency contributes to bone loss by increasing the production of pro-inflammatory cytokines by bone marrow and bone cells. Clinical and molecular evidence indicates that estrogen-regulated cytokines exert regulatory effects on bone turnover implicating their role as being the primary mediators of the accelerated bone loss at menopause. The current perspective on the role and interaction of cytokines such as IL-1, IL-4, IL-6, IL-17, TNF, IFN-γ and TGF-β in bone loss linked with estrogen deficiency is reviewed. Current treatment options and emerging drug therapies in the management of postmenopausal osteoporosis are also evaluated.

  6. Quantification of human immunoglobulins by semiautomatic polyethylene glycol precipitation radioimmunoassays. Estimation of circulating immune complexes and immunoglobulin synthesized in vitro

    International Nuclear Information System (INIS)

    Jensenius, J.C.; Siersted, H.C.; Johnstone, A.P.

    1983-01-01

    Simple, reliable semiautomatic radioimmunoassays have been developed for the measurement of human immunoglobulins (IgG, IgA, IgM, Igsub(kappa) and Igsub(lambda)). The assays are based on the separation of free from antibody-bound radiolabelled fragments of immunoglobulin by precipitation with 13% polyethylene glycol. The precipitate is harvested and washed on glass fibre filters by means of a commercial cell harvester. Radiolabelled lambda chain from Bence Jones urine was used for lambda chain assay and Fab'γ from pooled IgG for the kappa assay. Labelled Fab or Fc fragments of IgG, IgA and IgM were used for the class specific assays. Selected commercial antisera were used throughout. The sensitivity limits of the assays performed according to the standard procedure were about 20 ng Ig per ml. The assays have been used for the quantification of circulating immune complexes and both cellular and secreted immunoglobulin produced in cell cultures. The results demonstrate the importance of the simultaneous quantification by L chain and H chain specific assays. (Auth.)

  7. Blockade of Toll-like receptor 2 prevents spontaneous cytokine release from rheumatoid arthritis ex vivo synovial explant cultures

    LENUS (Irish Health Repository)

    Nic An Ultaigh, Sinead

    2011-02-23

    Abstract Introduction The aim of this study was to examine the effect of blocking Toll-like receptor 2 (TLR2) in rheumatoid arthritis (RA) synovial cells. Methods RA synovial tissue biopsies, obtained under direct visualization at arthroscopy, were established as synovial explant cultures ex vivo or snap frozen for immunohistology. Mononuclear cell cultures were isolated from peripheral blood and synovial fluid of RA patients. Cultures were incubated with the TLR1\\/2 ligand, Pam3CSK4 (200 ng, 1 and 10 μg\\/ml), an anti-TLR2 antibody (OPN301, 1 μg\\/ml) or an immunoglobulin G (IgG) (1 μg\\/ml) matched control. The comparative effect of OPN301 and adalimumab (anti-tumour necrosis factor alpha) on spontaneous release of proinflammatory cytokines from RA synovial explants was determined using quantitative cytokine MSD multiplex assays or ELISA. OPN301 penetration into RA synovial tissue explants cultures was assessed by immunohistology. Results Pam3CSK4 significantly upregulated interleukin (IL)-6 and IL-8 in RA peripheral blood mononuclear cells (PBMCs), RA synovial fluid mononuclear cells (SFMCs) and RA synovial explant cultures (P < 0.05). OPN301 significantly decreased Pam3CSK4-induced cytokine production of tumour necrosis factor alpha (TNF-α), IL-1β, IL-6, interferon (IFN)-γ and IL-8 compared to IgG control in RA PBMCs and SFMCs cultures (all P < 0.05). OPN301 penetration of RA synovial tissue cultures was detected in the lining layer and perivascular regions. OPN301 significantly decreased spontaneous cytokine production of TNF-α, IL-1β, IFN-γ and IL-8 from RA synovial tissue explant cultures (all P < 0.05). Importantly, the inhibitory effect of OPN on spontaneous cytokine secretion was comparable to inhibition by anti-TNFα monoclonal antibody adalimumab. Conclusions These findings further support targeting TLR2 as a potential therapeutic agent for the treatment of RA.

  8. Cytokines: muscle protein and amino acid metabolism

    DEFF Research Database (Denmark)

    van Hall, Gerrit

    2012-01-01

    raises TNF-α and IL-6 to moderate levels, has only identified IL-6 as a potent cytokine, decreasing systemic amino acid levels and muscle protein metabolism. The marked decrease in circulatory and muscle amino acid concentrations was observed with a concomitant reduction in both the rates of muscle...... of IL-6 on the regulation of muscle protein metabolism but indirectly via IL-6 reducing amino acid availability. SUMMARY: Recent studies suggest that the best described cytokines TNF-α and IL-6 are unlikely to be the major direct mediators of muscle protein loss in inflammatory diseases. However...

  9. Cytokines and Organ Failure in Acute Pancreatitis

    DEFF Research Database (Denmark)

    Malmstrøm, Marie Louise; Hansen, Mark Berner; Andersen, Anders Møller

    2012-01-01

    renal, respiratory, and circulatory failure, as was the case for patients with multiorgan failure. Interleukin 18 levels were significantly elevated in renal and respiratory failure only. Tumor necrosis factor > was significantly elevated in all types of organ failures, except for intestinal failure....... Conclusions: Synchronous measurements of 4 cytokines demonstrated IL-6 and IL-8 to be predictive as early surrogate markers with regard to organ failures in AP. The fact that all of the cytokines were particularly elevated in patients with organ failures calls for evaluation of agents modifying the severe...

  10. Proinflammatory Cytokines as Regulators of Vaginal Microbiota.

    Science.gov (United States)

    Kremleva, E A; Sgibnev, A V

    2016-11-01

    It was shown that IL-1β, IL-8, and IL-6 in concentrations similar to those in the vagina of healthy women stimulated the growth of normal microflora (Lactobacillus spp.) and suppressed the growth and biofilm production by S. aureus and E. coli. On the contrary, these cytokines in higher concentrations typical of vaginal dysbiosis suppressed normal microflora and stimulated the growth of opportunistic microorganisms. TGF-β1 in both doses produced a stimulating effects on study vaginal microsymbionts. It is hypothesized that pro-inflammatory cytokines serve as the molecules of interspecies communication coordinating the interactions of all components of the vaginal symbiotic system.

  11. Evaluation of the transfer of immunoglobulin from colostrum anaerobic fermentation (colostrum silage) to newborn calves.

    Science.gov (United States)

    Saalfeld, Mara H; Pereira, Daniela I B; Borchardt, Jessica L; Sturbelle, Regis T; Rosa, Matheus C; Guedes, Marcio C; Gularte, Marcia A; Leite, Fábio P Leivas

    2014-11-01

    Colostrum silage is an anaerobic fermentation methodology of excess farm colostrum used to conserve and provide as milk replacement for calves. The present study aimed to evaluate the levels of immunoglobulins present in bovine colostrum silage and its absorption by newborn calves. The concentration of immunoglobulins was determined in fresh colostrum and colostrum silage stored for 12 months. The absorption of immunoglobulins by calves was assessed immediately after birth and 24 h after colostrum silage intake. The immunoglobulin levels were evaluated by ELISA. The results highlighted that colostrum silage kept similar levels of immunoglobulins as the ones in colostrum in natura, and can be transferred to newborn calves with similar amounts to calves fed with colostrum in natura. It is concluded that colostrum silage keeps viable immunoglobulins, and is able to transfer passive immunity to newborn calves. © 2014 Japanese Society of Animal Science.

  12. High prevalence of immunoglobulin A deficiency in patients with type 1 diabetes mellitus detected by ELISA

    Directory of Open Access Journals (Sweden)

    Loraine Farias Landgraf

    2008-03-01

    Full Text Available Objective: To measure serum levels of immunoglobulin A byimmunoenzymatic assay (ELISA in type 1 diabetes mellitus (DM-1patients and to verify the prevalence of immunoglobulin A deficiency(IgAD in diabetic patients. Methods: The serum immunoglobulin Alevel was determined in 149 DM-1 patients by three methods. IgADwas defined as serum immunoglobulin A level lower than 5 mg/dl.If serum immunoglobulin A level was undetectable by turbidimetry,radial immunodiffusion was performed in low plate concentration.For patients with undetectable serum immunoglobulin A levelby the two previous methods, quantification was performed byELISA. In patients with IgAD, the levels of immunoglobulins Gand M were measured by turbidimetry to exclude other humoralimmunodeficiencies. Results: Out of 149 DM-1 patients evaluated,141 (94.6% had normal serum immunoglobulin A levels byturbidimetry. Eight patients (5.3% had undetectable serumimmunoglobulin A levels by turbidimetry and radial immunodiffusion.In these eight patients, the determination of serum immunoglobulinA was performed by ELISA, a more sensitive method. Very lowlevels of serum immunoglobulin A were detected in these diabeticpatients. In all diabetic patients, immunoglobulins G and M werenormal for age by turbidimetry. All 150 patients of the Control Grouphad normal serum immunoglobulin A levels by ELISA. Conclusions:There was a significantly higher prevalence of immunoglobulindeficiency among DM-1 patients (5.3%. Measurement of serumimmunoglobulin A is necessary in all DM-1 particularly before someimmunoglobulin A antibody screening. Patients with IgAD may havefalse-negative results for celiac disease screening tests involvingimmunoglobulin A antiendomysium and antigliadin antibodies.

  13. Quantitative Analysis of Repertoire-Scale Immunoglobulin Properties in Vaccine-Induced B-Cell Responses

    Science.gov (United States)

    2017-05-10

    following the recombination of discrete variable (V), 41 diverse ( D ) and joining (J) immunoglobulin (Ig) gene segments into a diverse library of B-cells...Quantitative analysis of repertoire-scale immunoglobulin properties in vaccine-induced B-cell responses Ilja V. Khavrutskii1, Sidhartha Chaudhury*1...qualitative trends in immunoglobulin (Ig) properties, such as V-family usage or 21 somatic hypermutation (SHM) rates, and in reducing the complex Ig

  14. Unravelling Immunoglobulin G Fc N-Glycosylation: A Dynamic Marker Potentiating Predictive, Preventive and Personalised Medicine

    OpenAIRE

    Alyce Russell; Eric Adua; Ivo Ugrina; Simon Laws; Wei Wang

    2018-01-01

    Multiple factors influence immunoglobulin G glycosylation, which in turn affect the glycoproteins’ function on eliciting an anti-inflammatory or pro-inflammatory response. It is prudent to underscore these processes when considering the use of immunoglobulin G N-glycan moieties as an indication of disease presence, progress, or response to therapeutics. It has been demonstrated that the altered expression of genes that encode enzymes involved in the biosynthesis of immunoglobulin G N-glycans,...

  15. Complement receptor immunoglobulin: a control point in infection and immunity, inflammation and cancer.

    Science.gov (United States)

    Small, Annabelle Grace; Al-Baghdadi, Marwah; Quach, Alex; Hii, Charles; Ferrante, Antonio

    2016-01-01

    The B7 family-related protein, V-set and Ig domain (VSIG4) / Z39Ig / complement receptor immunoglobulin (CRIg), is a new player in the regulation of immunity to infection and inflammation. The unique features of this receptor as compared with classical complement receptors, CR3 and CR4, have heralded the emergence of new concepts in the regulation of innate and adaptive immunity. Its selective expression in tissue macrophages and dendritic cells has been considered of importance in host defence and in maintaining tolerance against self-antigens. Although a major receptor for phagocytosis of complement opsonised bacteria, its array of emerging functions which incorporates the immune suppressive and anti-inflammatory action of the receptor have now been realised. Accumulating evidence from mouse experimental models indicates a potential role for CRIg in protection against bacterial infection and inflammatory diseases, such as rheumatoid arthritis, type 1 diabetes and systemic lupus erythematosus, and also in promotion of tumour growth. CRIg expression can be considered as a control point in these diseases, through which inflammatory mediators, including cytokines, act. The ability of CRIg to suppress cytotoxic T cell proliferation and function may underlie its promotion of cancer growth. Thus, the unique properties of this receptor open up new avenues for understanding of the pathways that regulate inflammation during infection, autoimmunity and cancer with the potential for new drug targets to be identified. While some complement receptors may be differently expressed in mice and humans, as well as displaying different properties, mouse CRIg has a structure and function similar to the human receptor, suggesting that extrapolation to human diseases is appropriate. Furthermore, there is emerging evidence in human conditions that CRIg may be a valuable biomarker in infection and immunity, inflammatory conditions and cancer prognosis.

  16. INDICATORS OF IMMUNE STATUS, CYTOKINE PROFILE IN SICKLY CHILDREN AND OPTIMIZATION OF APPROACHES TO PREVENTION OF ARI

    Directory of Open Access Journals (Sweden)

    S. A. Sokolov

    2013-01-01

    Full Text Available The authors have investigated the level of lymphocyte subpopulation, immunoglobulins IgA, IgM, IgG and the concentration of 10 cytokines in blood serum of 67 sickly children. All of them have chronic somatic pathology. The authors have ascertained absence of significant differences in immunological indicators. When the level of subpopulation composition of lymphocytes and IgG, IgA, IgM in the blood serum is normal, such children have a higher concentration of antiphlogistic cytokines 1L-1β, IL-12p70, IL-8 whereas the balance of Th/Th2-cells is preserved. It is kept up by cytokines IL-2, IFN-γ, TNF-α, IL-4, IL-5, IL-10 inthe conditions of chronic inflammatory process. The maintenance of this balance is the main goal and it should provide the basis for immunological correction of sickly children with chronic somatic pathology. The most appropriate drug for immunological correction in our research is ribosomal immunоmodulator Ribomunyl.

  17. Use of intravenous immunoglobulin in neonates with haemolytic disease and immune thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Marković-Sovtić Gordana

    2013-01-01

    Full Text Available Background/Aim. Intravenous immunoglobulin is a blood product made of human polyclonal immunoglobulin G. The mode of action of intravenous immunoglobulin is very complex. It is indicated in treatment of neonatal immune thrombocytopenia and haemolytic disease of the newborn. The aim of the study was to present our experience in the use of intravenous immunoglobulin in a group of term neonates. Methods. We analysed all relevant clinical and laboratory data of 23 neonates who recieved intravenous immunoglobulin during their hospitalization in Neonatal Intensive Care Unit of Mother and Child Health Care Institute over a five year period, from 2006. to 2010. Results. There were 11 patients with haemolytic disease of the newborn and 12 neonates with immune thrombocytopenia. All of them recieved 1-2 g/kg intravenous immunoglobulin in the course of their treatment. There was no adverse effects of intravenous immunoglobulin use. The use of intravenous immunoglobulin led to an increase in platelet number in thrombocytopenic patients, whereas in those with haemolytic disease serum bilirubin level decreased significantly, so that some patients whose bilirubin level was very close to the exchange transfusion criterion, avoided this procedure. Conclusion. The use of intravenous immunoglobulin was shown to be an effective treatment in reducing the need for exchange transfusion, duration of phototherapy and the length of hospital stay in neonates with haemolytic disease. When used in treatment of neonatal immune thrombocytopenia, it leads to an increase in the platelet number, thus decreasing the risk of serious complications of thrombocytopenia.

  18. Production of non-stimulatory immunoglobulins that inhibit TSH binding in Graves' disease after radioiodine administration

    International Nuclear Information System (INIS)

    Bech, K.; Bliddal, H.; Siersbaek-Nielsen, K.; Friis, T.

    1982-01-01

    The effect of single dose of 131 I upon thyroid stimulating immunoglobulins has been studied in twenty-two patients with Graves' disease. The thyroid stimulating immunoglobulins were assessed by parallel measurements of thyrotrophin receptor binding inhibitory immunoglobulins (TBII) and of thyroid adenylate cyclase stimulating immunoglobulins (TACSI) in serum by radioreceptor assay and stimulation of adenylate cyclase respectively. The present study thus confirms that radioiodine therapy is followed by an increase of TBII and TACSI in most patients with Graves' disease. The level of TBII can probably provide a marker for development of hypothyroidism following 131 I therapy and might be involved in its pathogenesis. (author)

  19. Unravelling Immunoglobulin G Fc N-Glycosylation: A Dynamic Marker Potentiating Predictive, Preventive and Personalised Medicine.

    Science.gov (United States)

    Russell, Alyce; Adua, Eric; Ugrina, Ivo; Laws, Simon; Wang, Wei

    2018-01-29

    Multiple factors influence immunoglobulin G glycosylation, which in turn affect the glycoproteins' function on eliciting an anti-inflammatory or pro-inflammatory response. It is prudent to underscore these processes when considering the use of immunoglobulin G N -glycan moieties as an indication of disease presence, progress, or response to therapeutics. It has been demonstrated that the altered expression of genes that encode enzymes involved in the biosynthesis of immunoglobulin G N -glycans, receptors, or complement factors may significantly modify immunoglobulin G effector response, which is important for regulating the immune system. The immunoglobulin G N -glycome is highly heterogenous; however, it is considered an interphenotype of disease (a link between genetic predisposition and environmental exposure) and so has the potential to be used as a dynamic biomarker from the perspective of predictive, preventive, and personalised medicine. Undoubtedly, a deeper understanding of how the multiple factors interact with each other to alter immunoglobulin G glycosylation is crucial. Herein we review the current literature on immunoglobulin G glycoprotein structure, immunoglobulin G Fc glycosylation, associated receptors, and complement factors, the downstream effector functions, and the factors associated with the heterogeneity of immunoglobulin G glycosylation.

  20. Unravelling Immunoglobulin G Fc N-Glycosylation: A Dynamic Marker Potentiating Predictive, Preventive and Personalised Medicine

    Directory of Open Access Journals (Sweden)

    Alyce Russell

    2018-01-01

    Full Text Available Multiple factors influence immunoglobulin G glycosylation, which in turn affect the glycoproteins’ function on eliciting an anti-inflammatory or pro-inflammatory response. It is prudent to underscore these processes when considering the use of immunoglobulin G N-glycan moieties as an indication of disease presence, progress, or response to therapeutics. It has been demonstrated that the altered expression of genes that encode enzymes involved in the biosynthesis of immunoglobulin G N-glycans, receptors, or complement factors may significantly modify immunoglobulin G effector response, which is important for regulating the immune system. The immunoglobulin G N-glycome is highly heterogenous; however, it is considered an interphenotype of disease (a link between genetic predisposition and environmental exposure and so has the potential to be used as a dynamic biomarker from the perspective of predictive, preventive, and personalised medicine. Undoubtedly, a deeper understanding of how the multiple factors interact with each other to alter immunoglobulin G glycosylation is crucial. Herein we review the current literature on immunoglobulin G glycoprotein structure, immunoglobulin G Fc glycosylation, associated receptors, and complement factors, the downstream effector functions, and the factors associated with the heterogeneity of immunoglobulin G glycosylation.

  1. Improved purification of immunoglobulin G from plasma by mixed-mode chromatography.

    Science.gov (United States)

    Chai, Dong-Sheng; Sun, Yan; Wang, Xiao-Ning; Shi, Qing-Hong

    2014-12-01

    Efficient loading of immunoglobulin G in mixed-mode chromatography is often a serious bottleneck in the chromatographic purification of immunoglobulin G. In this work, a mixed-mode ligand, 4-(1H-imidazol-1-yl) aniline, was coupled to Sepharose Fast Flow to fabricate AN SepFF adsorbents with ligand densities of 15-64 mmol/L, and the chromatographic performances of these adsorbents were thoroughly investigated to identify a feasible approach to improve immunoglobulin G purification. The results indicate that a critical ligand density exists for immunoglobulin G on the AN SepFF adsorbents. Above the critical ligand density, the adsorbents showed superior selectivity to immunoglobulin G at high salt concentrations, and also exhibited much higher dynamic binding capacities. For immunoglobulin G purification, both the yield and binding capacity increased with adsorbent ligand density along with a decrease in purity. It is difficult to improve the binding capacity, purity, and yield of immunoglobulin G simultaneously in AN SepFF chromatography. By using tandem AN SepFF chromatography, a threefold increase in binding capacity as well as high purity and yield of immunoglobulin G were achieved. Therefore, the tandem chromatography demonstrates that AN SepFF adsorbent is a practical and feasible alternative to MEP HyperCel adsorbents for immunoglobulin G purification. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Tropism and Infectivity of Influenza Virus, Including Highly Pathogenic Avian H5N1 Virus, in Ferret Tracheal Differentiated Primary Epithelial Cell Cultures

    Science.gov (United States)

    Zeng, Hui; Goldsmith, Cynthia S.; Maines, Taronna R.; Belser, Jessica A.; Gustin, Kortney M.; Pekosz, Andrew; Zaki, Sherif R.; Katz, Jacqueline M.

    2013-01-01

    Tropism and adaptation of influenza viruses to new hosts is partly dependent on the distribution of the sialic acid (SA) receptors to which the viral hemagglutinin (HA) binds. Ferrets have been established as a valuable in vivo model of influenza virus pathogenesis and transmission because of similarities to humans in the distribution of HA receptors and in clinical signs of infection. In this study, we developed a ferret tracheal differentiated primary epithelial cell culture model that consisted of a layered epithelium structure with ciliated and nonciliated cells on its apical surface. We found that human-like (α2,6-linked) receptors predominated on ciliated cells, whereas avian-like (α2,3-linked) receptors, which were less abundant, were presented on nonciliated cells. When we compared the tropism and infectivity of three human (H1 and H3) and two avian (H1 and H5) influenza viruses, we observed that the human influenza viruses primarily infected ciliated cells and replicated efficiently, whereas a highly pathogenic avian H5N1 virus (A/Vietnam/1203/2004) replicated efficiently within nonciliated cells despite a low initial infection rate. Furthermore, compared to other influenza viruses tested, VN/1203 virus replicated more efficiently in cells isolated from the lower trachea and at a higher temperature (37°C) compared to a lower temperature (33°C). VN/1203 virus infection also induced higher levels of immune mediator genes and cell death, and virus was recovered from the basolateral side of the cell monolayer. This ferret tracheal differentiated primary epithelial cell culture system provides a valuable in vitro model for studying cellular tropism, infectivity, and the pathogenesis of influenza viruses. PMID:23255802

  3. Synthetic Long Peptide Influenza Vaccine Containing Conserved T and B Cell Epitopes Reduces Viral Load in Lungs of Mice and Ferrets.

    Directory of Open Access Journals (Sweden)

    S K Rosendahl Huber

    Full Text Available Currently licensed influenza vaccines mainly induce antibodies against highly variable epitopes. Due to antigenic drift, protection is subtype or strain-specific and regular vaccine updates are required. In case of antigenic shifts, which have caused several pandemics in the past, completely new vaccines need to be developed. We set out to develop a vaccine that provides protection against a broad range of influenza viruses. Therefore, highly conserved parts of the influenza A virus (IAV were selected of which we constructed antibody and T cell inducing peptide-based vaccines. The B epitope vaccine consists of the highly conserved HA2 fusion peptide and M2e peptide coupled to a CD4 helper epitope. The T epitope vaccine comprises 25 overlapping synthetic long peptides of 26-34 amino acids, thereby avoiding restriction for a certain MHC haplotype. These peptides are derived from nucleoprotein (NP, polymerase basic protein 1 (PB1 and matrix protein 1 (M1. C57BL/6 mice, BALB/c mice, and ferrets were vaccinated with the B epitopes, 25 SLP or a combination of both. Vaccine-specific antibodies were detected in sera of mice and ferrets and vaccine-specific cellular responses were measured in mice. Following challenge, both mice and ferrets showed a reduction of virus titers in the lungs in response to vaccination. Summarizing, a peptide-based vaccine directed against conserved parts of influenza virus containing B and T cell epitopes shows promising results for further development. Such a vaccine may reduce disease burden and virus transmission during pandemic outbreaks.

  4. Immunoglobulin production induced in vitro by glucocorticoid hormones: T cell-dependent stimulation of immunoglobulin production without B cell proliferation in cultures of human peripheral blood lymphocytes

    International Nuclear Information System (INIS)

    Grayson, J.; Dooley, N.J.; Koski, I.R.; Blaese, R.M.

    1981-01-01

    The direct effects of steroid hormones on the production of immunoglobulins and DNA synthesis by human T and B lymphocytes was evaluated in cultures of peripheral blood mononuclear cells. As detected by a reverse hemolytic plaque assay, the addition of 0.1 mM to 10 nM hydrocortisone to lymphocytes in culture in the absence of other stimulants or mitogens, resulted in the dramatic induction of immunoglobulin production with responses comparable to those seen in similar cultures stimulated with pokeweed mitogen. Steroid-stimulated immunoglobulin production was first seen after 48 h and peaked at 8-10 d of culture. The production of IgG, IgA, and IgM was induced following incubation with steroid. Glucocorticoids, but not estrogens or androgens, were capable of mediating this effect, and only compounds with affinity for the glucocorticoid receptor were active. The induction of immunoglobulin production was dependent on both T cells and monocytes; cultures depleted of either cell type did not produce immunoglobulin when stimulated with glucocorticoid hormones. Proliferation of B cells or T cells could not be detected by [/sup 3/H]thymidine incorporation or total cell recovery from steroid-stimulated cultures, even though such cultures demonstrated marked increases in immunoglobulin production. The mechanism responsible for this functional maturation of B cells to become high rate immunoglobulin producing cells is as yet undefined, although it appears to involve more than merely steroid mediated inactivation of suppressor T cells

  5. Cytokines in atherosclerosis: an intricate balance

    NARCIS (Netherlands)

    Boshuizen, M.C.S.

    2016-01-01

    Atherosclerosis is the underlying pathology in the majority of clinical manifestations of cardiovascular diseases, which are nowadays the main global cause of mortality. Atherosclerosis is a lipid-driven chronic inflammatory disease of the arterial wall. This inflammatory response, with cytokines as

  6. Cytokine gene expression of peripheral blood lymphocytes ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-03-20

    Mar 20, 2009 ... Key words: Lipopolysaccharide, lymphocytes, TLRs, cytokines. INTRODUCTION. Lipopolysaccharide (LPS), a predominant glycolipid in the outer membranes of Gam-negative bacteria, stimulates monocyte, macrophages, and neutrophils and increase expression of cell adhesion molecules (Trent et al., ...

  7. Study of cytokines microenvironment during autoimmune diseases ...

    African Journals Online (AJOL)

    22, IL-23, TNF-α and TGF-β) were determined. We used the immunoenzymatic technology to assess the titer of cytokines. We found that there was no significant variation of TNF-α level in normal controls and autoimmune diseases ...

  8. Current status and challenges of cytokine pharmacology

    Czech Academy of Sciences Publication Activity Database

    Zídek, Zdeněk; Anzenbacher, P.; Kmoníčková, Eva

    2009-01-01

    Roč. 157, č. 3 (2009), s. 342-361 ISSN 0007-1188 R&D Projects: GA ČR GA305/08/0535; GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z50390512 Keywords : cytokines * immunotherapy * immunopharmacology Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 5.204, year: 2009

  9. Immunodeficiency secondary to anti-cytokine autoantibodies

    Science.gov (United States)

    Browne, Sarah K.; Holland, Steven M.

    2011-01-01

    Purpose of review Anti-cytokine autoantibodies are an important and emerging mechanism of disease pathogenesis. We will review the clinical and laboratory features of syndromes in which immunodeficiency is caused by or associated with neutralizing anti-cytokine autoantibodies. Recent findings A growing number of patients have been described who demonstrate unique infectious phenotypes associated with neutralizing autoantibodies that target a particular cytokine known to participate in host defense against the offending organism. Examples include anti-granulocyte macrophage-colony stimulating factor (GM-CSF) autoantibodies and pulmonary alveolar proteinosis; anti-interferon(IFN)-γ autoantibodies and disseminated nontuberculous mycobacteria(NTM); anti-(interleukin)IL-6 autoantibodies and severe staphylococcal skin infection; anti-IL-17A, antiIL-17F or anti-IL-22 autoantibodies in patients with mucocutaneous candidiasis in the setting of both the autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy (APECED) syndrome and in cases of thymoma. Summary Anti-cytokine autoantibodies have manifestations that are diverse, ranging from asymptomatic to life-threatening. These emerging and fascinating causes of acquired immunodeficiency may explain some previously idiopathic syndromes. PMID:20966748

  10. Omics and cytokine discovery in fish

    NARCIS (Netherlands)

    Jacobson, Gregory; Muncaster, Simon; Mensink, Koen; Forlenza, Maria; Elliot, Nick; Broomfield, Grant; Signal, Beth; Bird, Steve

    2017-01-01

    A continued programme of research is essential to overcome production bottlenecks in any aquacultured fish species. Since the introduction of genetic and molecular techniques, the quality of immune research undertaken in fish has greatly improved. Thousands of species specific cytokine genes have

  11. Proinflammatory cytokine responses in patients with psoriasis.

    Science.gov (United States)

    Kouris, Anargyros; Pistiki, Aikaterini; Katoulis, Alexandros; Georgitsi, Marianna; Giatrakou, Sofia; Papadavid, Evangelia; Netea, Mihai G; Stavrianeas, Nikolaos; Giamarellos-Bourboulis, Evangelos J

    2014-01-01

    Psoriasis is one of the most common, immune-mediated, chronic inflammatory skin diseases. Proinflammatory cytokines play an important pathogenetic role at a local level. To assess whether the proinflammatory cytokines IL-1β, IL-6, IL-17, IL-22 and TNF-α are released systemically during psoriasis. Peripheral blood mononuclear cells (PBMCs) were isolated from 30 patients with psoriasis and 30 healthy volunteers. Cytokine production was assessed in supernatants using an enzyme immunoassay after stimulation of PBMCs with microbial stimuli. In addition, flow cytometry was used to determine the subsets of monocytes involved and the intracellular TNF-α production in monocytes. IL-17 levels were significantly higher in the supernatants of PBMCs from psoriatic patients after stimulation with phytohemagglutinin. TNF-α production was also significantly higher in cells from psoriatic patients after stimulation with all stimuli, as compared with health volunteers. Similar changes were not found for the other cytokines. A statistically significant difference was observed between patients and controls for inflammatory CD14(+)/CD16(+) monocytes (ppsoriasis. These results support the concept that there is a systemic, proinflammatory component in psoriasis.

  12. Cytokines and Immune Responses in Murine Atherosclerosis

    NARCIS (Netherlands)

    Kusters, Pascal J. H.; Lutgens, Esther

    2015-01-01

    Atherosclerosis is an inflammatory disease of the vessel wall characterized by activation of the innate immune system, with macrophages as the main players, as well as the adaptive immune system, characterized by a Th1-dominant immune response. Cytokines play a major role in the initiation and

  13. Cytokines as biomarkers of nanoparticle immunotoxicity.

    Science.gov (United States)

    Elsabahy, Mahmoud; Wooley, Karen L

    2013-06-21

    Nanoscale objects, whether of biologic origin or synthetically created, are being developed into devices for a variety of bionanotechnology diagnostic and pharmaceutical applications. However, the potential immunotoxicity of these nanomaterials and mechanisms by which they may induce adverse reactions have not received sufficient attention. Nanomaterials, depending on their characteristics and compositions, can interact with the immune system in several ways and either enhance or suppress immune system function. Cytokines perform pleiotropic functions to mediate and regulate the immune response and are generally recognized as biomarkers of immunotoxicity. While the specificity and validity of certain cytokines as markers of adverse immune response has been established for chemicals, small and macromolecular drugs, research on their applicability for predicting and monitoring the immunotoxicity of engineered nanomaterials is still ongoing. The goal of this review is to provide guidelines as to important cytokines that can be utilized for evaluating the immunotoxicity of nanomaterials and to highlight the role of those cytokines in mediating adverse reactions, which is of particular importance for the clinical development of nanopharmaceuticals and other nanotechnology-based products. Importantly, the rational design of nanomaterials of low immunotoxicity will be discussed, focusing on synthetic nanodevices, with emphasis on both the nanoparticle-forming materials and the embedded cargoes.

  14. Cytokines and immune surveillance in humans

    Science.gov (United States)

    Sonnenfeld, Gerald

    1994-01-01

    Evidence from both human and rodent studies has indicated that alterations in immunological parameters occur after space flight. Among the parameters shown, by us and others, to be affected is the production of interferons. Interferons are a family of cytokines that are antiviral and play a major role in regulating immune responses that control resistance to infection. Alterations in interferon and other cytokine production and activity could result in changes in immunity and a possible compromise of host defenses against both opportunistic and external infections. The purpose of the present study is to explore further the effects of space flight on cyotokines and cytokine-directed immunological function. Among the tests carried out are interferon-alpha production, interferon-gamma production, interleukin-1 and -2 production, signal transduction in neutrophils, signal transduction in monocytes, and monocyte phagocytic activity. The experiments will be performed using peripheral blood obtained from human subjects. It is our intent to eventually carry out these experiments using astronauts as subjects to determine the effects of space flight on cytokine production and activity. However, these subjects are not currently available. Until they become available, we will carry out these experiments using subjects maintained in the bed-rest model for microgravity.

  15. Cytokines as biomarkers of nanoparticle immunotoxicity

    Science.gov (United States)

    Elsabahy, Mahmoud; Wooley, Karen L.

    2013-01-01

    Nanoscale objects, whether of biologic origin or synthetically created, are being developed into devices for a variety of bionanotechnology diagnostic and pharmaceutical applications. However, the potential immunotoxicity of these nanomaterials and mechanisms by which they may induce adverse reactions have not received sufficient attention. Nanomaterials, depending on their characteristics and compositions, can interact with the immune system in several ways and either enhance or suppress immune system function. Cytokines perform pleiotropic functions to mediate and regulate the immune response and are generally recognized as biomarkers of immunotoxicity. While the specificity and validity of certain cytokines as markers of adverse immune response has been established for chemicals, small and macromolecular drugs, research on their applicability for predicting and monitoring the immunotoxicity of engineered nanomaterials is still ongoing. The goal of this review is to provide guidelines as to important cytokines that can be utilized for evaluating the immunotoxicity of nanomaterials and to highlight the role of those cytokines in mediating adverse reactions, which is of particular importance for the clinical development of nanopharmaceuticals and other nanotechnology-based products. Importantly, the rational design of nanomaterials of low immunotoxicity will be discussed, focusing on synthetic nanodevices, with emphasis on both the nanoparticle-forming materials and the embedded cargoes. PMID:23549679

  16. Cytokines in Sjögren's syndrome

    NARCIS (Netherlands)

    Roescher, N.; Tak, P. P.; Illei, G. G.

    2009-01-01

    Cytokines play a central role in the regulation of immunity and are often found to be deregulated in autoimmune diseases. Sjögren's syndrome is a chronic autoimmune disease characterized by inflammation and loss of secretory function of the salivary and lachrymal glands. This review highlights the

  17. Increased acid stability of the hemagglutinin protein enhances H5N1 influenza virus growth in the upper respiratory tract but is insufficient for transmission in ferrets.

    Science.gov (United States)

    Zaraket, Hassan; Bridges, Olga A; Duan, Susu; Baranovich, Tatiana; Yoon, Sun-Woo; Reed, Mark L; Salomon, Rachelle; Webby, Richard J; Webster, Robert G; Russell, Charles J

    2013-09-01

    Influenza virus entry is mediated by the acidic-pH-induced activation of hemagglutinin (HA) protein. Here, we investigated how a decrease in the HA activation pH (an increase in acid stability) influences the properties of highly pathogenic H5N1 influenza virus in mammalian hosts. We generated isogenic A/Vietnam/1203/2004 (H5N1) (VN1203) viruses containing either wild-type HA protein (activation pH 6.0) or an HA2-K58I point mutation (K to I at position 58) (activation pH 5.5). The VN1203-HA2-K58I virus had replication kinetics similar to those of wild-type VN1203 in MDCK and normal human bronchial epithelial cells and yet had reduced growth in human alveolar A549 cells, which were found to have a higher endosomal pH than MDCK cells. Wild-type and HA2-K58I viruses promoted similar levels of morbidity and mortality in C57BL/6J mice and ferrets, and neither virus transmitted efficiently to naive contact cage-mate ferrets. The acid-stabilizing HA2-K58I mutation, which diminishes H5N1 replication and transmission in ducks, increased the virus load in the ferret nasal cavity early during infection while simultaneously reducing the virus load in the lungs. Overall, a single, acid-stabilizing mutation was found to enhance the growth of an H5N1 influenza virus in the mammalian upper respiratory tract, and yet it was insufficient to enable contact transmission in ferrets in the absence of additional mutations that confer α(2,6) receptor binding specificity and remove a critical N-linked glycosylation site. The information provided here on the contribution of HA acid stability to H5N1 influenza virus fitness and transmissibility in mammals in the background of a non-laboratory-adapted virus provides essential information for the surveillance and assessment of the pandemic potential of currently circulating H5N1 viruses.

  18. Highly Pathogenic Avian Influenza H5N6 Viruses Exhibit Enhanced Affinity for Human Type Sialic Acid Receptor and In-Contact Transmission in Model Ferrets.

    Science.gov (United States)

    Sun, Honglei; Pu, Juan; Wei, Yandi; Sun, Yipeng; Hu, Jiao; Liu, Litao; Xu, Guanlong; Gao, Weihua; Li, Chong; Zhang, Xuxiao; Huang, Yinhua; Chang, Kin-Chow; Liu, Xiufan; Liu, Jinhua

    2016-07-15

    Since May 2014, highly pathogenic avian influenza H5N6 virus has been reported to cause six severe human infections three of which were fatal. The biological properties of this subtype, in particular its relative pathogenicity and transmissibility in mammals, are not known. We characterized the virus receptor-binding affinity, pathogenicity, and transmissibility in mice and ferrets of four H5N6 isolates derived from waterfowl in China from 2013-2014. All four H5N6 viruses have acquired a binding affinity for human-like SAα2,6Gal-linked receptor to be able to attach to human tracheal epithelial and alveolar cells. The emergent H5N6 viruses, which share high sequence similarity with the human isolate A/Guangzhou/39715/2014 (H5N6), were fully infective and highly transmissible by direct contact in ferrets but showed less-severe pathogenicity than the parental H5N1 virus. The present results highlight the threat of emergent H5N6 viruses to poultry and human health and the need to closely track their continual adaptation in humans. Extended epizootics and panzootics of H5N1 viruses have led to the emergence of the novel 2.3.4.4 clade of H5 virus subtypes, including H5N2, H5N6, and H5N8 reassortants. Avian H5N6 viruses from this clade have caused three fatalities out of six severe human infections in China since the first case in 2014. However, the biological properties of this subtype, especially the pathogenicity and transmission in mammals, are not known. Here, we found that natural avian H5N6 viruses have acquired a high affinity for human-type virus receptor. Compared to the parental clade 2.3.4 H5N1 virus, emergent H5N6 isolates showed less severe pathogenicity in mice and ferrets but acquired efficient in-contact transmission in ferrets. These findings suggest that the threat of avian H5N6 viruses to humans should not be ignored. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  19. Molecular imaging reveals a progressive pulmonary inflammation in lower airways in ferrets infected with 2009 H1N1 pandemic influenza virus.

    Directory of Open Access Journals (Sweden)

    Colleen B Jonsson

    Full Text Available Molecular imaging has gained attention as a possible approach for the study of the progression of inflammation and disease dynamics. Herein we used [(18F]-2-deoxy-2-fluoro-D-glucose ([(18F]-FDG as a radiotracer for PET imaging coupled with CT (FDG-PET/CT to gain insight into the spatiotemporal progression of the inflammatory response of ferrets infected with a clinical isolate of a pandemic influenza virus, H1N1 (H1N1pdm. The thoracic regions of mock- and H1N1pdm-infected ferrets were imaged prior to infection and at 1, 2, 3 and 6 days post-infection (DPI. On 1 DPI, FDG-PET/CT imaging revealed areas of consolidation in the right caudal lobe which corresponded with elevated [(18F]-FDG uptake (maximum standardized uptake values (SUVMax, 4.7-7.0. By days 2 and 3, consolidation (CT and inflammation ([(18F]-FDG appeared in the left caudal lobe. By 6 DPI, CT images showed extensive areas of patchy ground-glass opacities (GGO and consolidations with the largest lesions having high SUVMax (6.0-7.6. Viral shedding and replication were detected in most nasal, throat and rectal swabs and nasal turbinates and lungs on 1, 2 and 3 DPI, but not on day 7, respectively. In conclusion, molecular imaging of infected ferrets revealed a progressive consolidation on CT with corresponding [(18F]-FDG uptake. Strong positive correlations were measured between SUVMax and bronchiolitis-related pathologic scoring (Spearman's ρ = 0.75. Importantly, the extensive areas of patchy GGO and consolidation seen on CT in the ferret model at 6 DPI are similar to that reported for human H1N1pdm infections. In summary, these first molecular imaging studies of lower respiratory infection with H1N1pdm show that FDG-PET can give insight into the spatiotemporal progression of the inflammation in real-time.

  20. Anti-inflammatory activity of sublingual immunoglobulin (SLIG) in a murine model of allergen-driven airway inflammation.

    Science.gov (United States)

    Batard, T; Zimmer, A; Nony, E; Bouley, J; Airouche, S; Luce, S; Turfkruyer, M; Tourdot, S; Mascarell, L; Moingeon, P

    2012-08-17

    Intravenous immunoglobulin (IVIG) displays anti-inflammatory activities in many diseases. Subcutaneous administration of anti-IgE in humans provides benefit in severe persistent allergic asthma. Given the well established efficacy of sublingual allergen immunotherapy in respiratory type I allergies, we investigated the therapeutic potential of sublingual immunoglobulin (SLIG), most particularly anti-IgE SLIG, in a murine model of allergen-driven airway inflammation. BALB/c mice sensitized with ovalbumin (OVA) were treated sublingually with rat monoclonal IgG1 or IgG2a, either directed to mouse IgE or with no reported specificity. Airway hyperresponsiveness (AHR) was assessed by whole body plethysmography, and eosinophil infiltrates were characterized in bronchial alveolar lavages (BAL). OVA-specific antibody and T cell responses were analyzed in sera and saliva or lung and draining lymph nodes, by ELISA or CBA measurement of cytokine production, respectively. AHR and BAL eosinophil infiltrates were substantially decreased in mice treated sublingually with particulate OVA (positive control), as well as in animals receiving various rat IgG1, irrespective of their specificity for murine IgE. In contrast, no improvement was observed in mice treated with PBS (negative control) or various rat IgG2a. SLIG anti-inflammatory activity is not related to a downregulation of Th2, Th17 or an induction of Foxp3(+) CD4(+) regulatory T cell responses. Mass spectrometry analysis of glycan moieties, such as sialic acid, suggests that the differential efficacy of rat IgG1 and IgG2a is not related to their capacity to interact with lectins borne by oral immune cells. In a murine model of allergen-driven airway inflammation, SLIG exhibits an anti-inflammatory activity irrespective of the immunoglobulin specificity, and in the absence of allergen. As a noninvasive approach, SLIG deserves to be further studied as a treatment for other inflammatory diseases beyond allergic asthma