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Sample records for ferret immunoglobulins cytokines

  1. Generation of Monoclonal Antibodies against Immunoglobulin Proteins of the Domestic Ferret (Mustela putorius furo)

    Science.gov (United States)

    2017-01-01

    The domestic ferret (Mustela putorius furo) serves as an animal model for the study of several viruses that cause human disease, most notably influenza. Despite the importance of this animal model, characterization of the immune response by flow cytometry (FCM) is severely hampered due to the limited number of commercially available reagents. To begin to address this unmet need and to facilitate more in-depth study of ferret B cells including the identification of antibody-secreting cells, eight unique murine monoclonal antibodies (mAb) with specificity for ferret immunoglobulin (Ig) were generated using conventional B cell hybridoma technology. These mAb were screened for reactivity against ferret peripheral blood mononuclear cells by FCM and demonstrate specificity for CD79β+ B cells. Several of these mAb are specific for the light chain of surface B cell receptor (BCR) and enable segregation of kappa and lambda B cells. Additionally, a mAb that yielded surface staining of nearly all surface BCR positive cells (i.e., pan ferret Ig) was generated. Collectively, these MαF-Ig mAb offer advancement compared to the existing portfolio of polyclonal anti-ferret Ig detection reagents and should be applicable to a wide array of immunologic assays including the identification of antibody-secreting cells by FCM. PMID:28286781

  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. Successive immunoglobulin and cytokine expression in the small intestine of juvenile chicken

    NARCIS (Netherlands)

    Lammers, A.; Wieland, W.H.; Kruijt, L.; Jansma, A.; Straetemans, T.; Schots, A.; Hartog, den C.G.; Parmentier, H.K.

    2010-01-01

    The intestinal mucosa is of major importance for immune development. To further study the ontogeny of avian mucosal immunity, mRNA levels of IgM, IgY and IgA, the polymeric immunoglobulin receptor (pIgR) and a number of cytokines were determined at different ages in jejunum and ileum of

  4. 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...

  5. 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.

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

    International Nuclear Information System (INIS)

    Fliss-Jaber, Lilia; Houissa-Kastally, Radhia; Bouzouita, Kamel; Khediri, Naceur; Khelifa, Ridha

    2004-01-01

    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). 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. 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 < 0,0001) than their PBL. On the other hand, patients PBL produced significantly higher levels of IL-2 (p = 0,022), IL-10 (p = 0,016) and IgM (p = 0,004) than those of controls. No significant differences for IL-6 and IgA were observed. 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

  7. 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.

  8. [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.

  9. Effects of Scutellariae radix and Aloe vera gel extracts on immunoglobulin E and cytokine levels in atopic dermatitis NC/Nga mice.

    Science.gov (United States)

    Kim, Jinkyung; Lee, In seok; Park, Soojin; Choue, Ryowon

    2010-11-11

    The present study aimed to investigate the effects of Scutellariae radix (SR) and Aloe vera gel (AV), alone or in combination, on levels of immunoglobulin E (IgE) and inflammatory cytokines in spontaneous atopic dermatitis(AD)-like skin lesions. After spontaneous AD-like skin lesion was developed by adaptation to conventional conditions, mice were randomly assigned to control, SR (50 mg/kg, p.o.), AV (0.8 mg/kg, p.o.) and SRAV (50 mg of SR and 0.8 mg of AV/kg, p.o.) groups, and were treated for 6 weeks. SR and SRAV suppressed IL-5 levels compared with control, but had no effects on IgE levels (P<0.05). AV increased IgE levels, but decreased both IL-5 and IL-10 compared with control (P<0.05). These results suggest that SR and AV modulate immunological responses in AD, mainly through influencing IL-5 or IL-10 levels. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  10. 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

  11. 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, ...... 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......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...

  12. Endocrine diseases in ferrets

    NARCIS (Netherlands)

    Schoemaker, N.J.; van Zeeland, Y.R.A.

    2013-01-01

    SUMMARY Endocrine diseases are among the most commonly seen conditions in ferrets. Tumours of the islet cells in the pancreas, referred to as insulinomas, and tumours of the adrenal glands, referred to as hyperadrenocorticism, are more commonly described in this species than in any other species.

  13. FERRET data analysis code

    International Nuclear Information System (INIS)

    Schmittroth, F.

    1979-09-01

    A documentation of the FERRET data analysis code is given. The code provides a way to combine related measurements and calculations in a consistent evaluation. Basically a very general least-squares code, it is oriented towards problems frequently encountered in nuclear data and reactor physics. A strong emphasis is on the proper treatment of uncertainties and correlations and in providing quantitative uncertainty estimates. Documentation includes a review of the method, structure of the code, input formats, and examples

  14. 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...

  15. 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...

  16. Vaccination of Ferrets for Rabies and Distemper.

    Science.gov (United States)

    Wade, Laura L

    2018-01-01

    Companion ferrets need to be vaccinated against 2 viral diseases that cause neurologic illness: canine distemper and rabies. Although not common in ferrets, both viruses are fatal in ferrets and rabies virus is also fatal in humans. In this article, we provide a basic review of the 2 diseases, highlighting key neurologic concerns. We also review and update current vaccine concerns from a practitioner's perspective, including available vaccines, vaccine schedule recommendations, vaccine reactions, and risk assessment. Last, we mention the ferret and its use in cutting-edge vaccine development. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Fish Immunoglobulins

    OpenAIRE

    Sara Mashoof; Michael F. Criscitiello

    2016-01-01

    The B cell receptor and secreted antibody are at the nexus of humoral adaptive immunity. In this review, we summarize what is known of the immunoglobulin genes of jawed cartilaginous and bony fishes. We focus on what has been learned from genomic or cDNA sequence data, but where appropriate draw upon protein, immunization, affinity and structural studies. Work from major aquatic model organisms and less studied comparative species are both included to define what is the rule for an immunoglob...

  18. Pathogenesis, humoral immune responses and transmission between co-housed animals in a ferret model of human RSV infection.

    Science.gov (United States)

    Chan, Kok Fei; Carolan, Louise A; Druce, Julian; Chappell, Keith; Watterson, Daniel; Young, Paul; Korenkov, Daniil; Subbarao, Kanta; Barr, Ian G; Laurie, Karen L; Reading, Patrick C

    2017-11-29

    Small animal models have been used to obtain many insights regarding the pathogenesis and immune responses induced following infection with human respiratory syncytial virus (hRSV). Amongst those described to date, infections in cotton rats, mice, guinea pigs, chinchillas and Syrian hamsters with hRSV strains Long and/or A2 have been well characterised, although clinical isolates have also been examined. Ferrets are also susceptible to hRSV infection but the pathogenesis and immune responses elicited following infection have not been well characterised. Herein, we describe the infection of adult ferrets with hRSV Long or A2 via the intranasal route and characterised virus replication, as well as cytokine induction, in the upper and lower airways. Virus replication and cytokine induction during the acute phase of infection (days 0-15 post-infection) were similar between the two strains and both elicited high levels of F glycoprotein-specific binding and neutralising antibodies following virus clearance (days 16-22 post-infection). Importantly, we demonstrate transmission from experimentally infected donor ferrets to co-housed naïve recipients and have characterised virus replication and cytokine induction in the upper airways of infected contact animals. Together, these studies provide a direct comparison of the pathogenesis of hRSV Long and A2 in ferrets and highlight the potential of this animal model to study serological responses and examine interventions that limit transmission of hRSV. IMPORTANCE Ferrets have been widely used to study pathogenesis, immunity and transmission following human influenza virus infections, however far less is known regarding the utility of the ferret model to study hRSV infections. Following intranasal (IN) infection of adult ferrets with the well characterised Long or A2 strains of hRSV, we report virus replication and cytokine induction in the upper and lower airways, as well as the development of virus-specific humoral responses

  19. Information on black-footed ferret biology collected within the framework of ferret conservation

    Science.gov (United States)

    Biggins, Dean E.

    2012-01-01

    Once feared to be extinct, black-footed ferrets (Mustela nigripes) were rediscovered near Meeteetse, Wyoming, in 1981, resulting in renewed conservation and research efforts for this highly endangered species. A need for information directly useful to recovery has motivated much monitoring of ferrets since that time, but field activities have enabled collection of data relevant to broader biological themes. This special feature is placed in a context of similar books and proceedings devoted to ferret biology and conservation. Articles include general observations on ferrets, modeling of potential impacts of ferrets on prairie dogs (Cynomys spp.), discussions on relationships of ferrets to prairie dog habitats at several spatial scales (from individual burrows to patches of burrow systems) and a general treatise on the status of black-footed ferret recovery.

  20. Immunoglobulins in Cerebrospinal Fluid

    DEFF Research Database (Denmark)

    Sellebjerg, Finn Thorup

    2015-01-01

    immunoglobulin synthesis. Intrathecally synthesised immunoglobulins are usually of restricted clonality, and electrophoresis-based methods can be used for detecting this in the form of oligoclonal bands. These methods depend on comparing paired CSF and blood samples. Qualitative analyses for the assessment......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...

  1. 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.

  2. 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

  3. Intervertebral disk prolapse in a ferret.

    Science.gov (United States)

    Morera, Neus; Valls, Xavier; Mascort, Joan

    2006-09-01

    This case report describes the diagnosis and resolution of an inter-vertebral disk prolapse in a 6-year-old ferret. No predisposing causes were found in the patient's history. A right hemilaminectomy, performed 1 week after presentation, was chosen to treat the patient surgically, and complete remission of clinical signs was achieved 2 months after presentation.

  4. Distichiasis in a ferret (Mustela putorius furo)

    NARCIS (Netherlands)

    Verboven, CAPM; Djajadiningrat-Laanen, S.C.; Kitslaar, W.J.P.; Grinwis, G.C.M.; Schoemaker, N.J.; Boevé, M.H.

    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

  5. 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.

  6. Parvovirus-associated syndrome (Aleutian disease) in two ferrets.

    Science.gov (United States)

    Palley, L S; Corning, B F; Fox, J G; Murphy, J C; Gould, D H

    1992-07-01

    There is a paucity of information regarding natural Aleutian disease, caused by a parvovirus in ferrets. With the increasing popularity of ferrets as household pets and laboratory animals, and with the advent of a USDA-approved rabies vaccine, the occurrence and the etiopathogenesis of naturally acquired diseases in ferrets needs to be documented. We present the clinical and laboratory findings associated with Aleutian disease in 2 domestic ferrets, one with the chronic wasting form of the disease and one with the central nervous system form.

  7. Comparison of SAND-II and FERRET

    International Nuclear Information System (INIS)

    Wootan, D.W.; Schmittroth, F.

    1981-01-01

    A comparison was made of the advantages and disadvantages of two codes, SAND-II and FERRET, for determining the neutron flux spectrum and uncertainty from experimental dosimeter measurements as anticipated in the FFTF Reactor Characterization Program. This comparison involved an examination of the methodology and the operational performance of each code. The merits of each code were identified with respect to theoretical basis, directness of method, solution uniqueness, subjective influences, and sensitivity to various input parameters

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

    Science.gov (United States)

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

    1998-12-01

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

  9. Cystic urogenital anomalies in ferrets (Mustela putorius furo).

    Science.gov (United States)

    Li, X; Fox, J G; Erdman, S E; Lipman, N S; Murphy, J C

    1996-03-01

    Single or multiple semispherical to bilobulated fluid-filled cystic structures of variable size were observed on the dorsal aspects of the urinary bladder of four male and two female ferrets (Mustela putorius furo). All ferrets had been neutered. On physical examination, the cysts were palpated as caudal abdominal masses. Three of the six ferrets presented with dysuria, and two ferrets had signs compatible with endocrine dysfunction. Adrenal cortical hyperplasia or neoplasia were observed in all of the five ferrets examined. Sex hormones assayed in one of the six ferrets revealed elevated levels of serum estrodiol. The posterior aspect of the cysts was located on and/or attached to the trigone or neck of the bladder, with variable intraluminal communication with the bladder and/or the urethra. The anterior aspect of the cysts projected dorsally or dorsocranially into the caudal abdomen. The cysts were thin walled and contained urinelike fluid (n = 5) or viscous yellow fluid (n = 1). Histologically, the cyst walls were composed of three layers, epithelium, muscle, and serosa, with fibrovascular stroma between layers. The epithelium consisted of simple to stratified transitional, columnar, or squamous epithelial cells. The muscular layer consisted of intermittent bundles and/or single to double layers of continuous to discontinuous smooth muscle. The serosal layer consisted of loose fibrous stroma covered by flattened mesothelial cells. The cystic anomalies in these ferrets were most likely derived from the urogenital glands/ducts or other remnants.

  10. 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

  11. 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....

  12. 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...

  13. 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.

  14. Behavioural benefits of multisensory processing in ferrets.

    Science.gov (United States)

    Hammond-Kenny, Amy; Bajo, Victoria M; King, Andrew J; Nodal, Fernando R

    2017-01-01

    Enhanced detection and discrimination, along with faster reaction times, are the most typical behavioural manifestations of the brain's capacity to integrate multisensory signals arising from the same object. In this study, we examined whether multisensory behavioural gains are observable across different components of the localization response that are potentially under the command of distinct brain regions. We measured the ability of ferrets to localize unisensory (auditory or visual) and spatiotemporally coincident auditory-visual stimuli of different durations that were presented from one of seven locations spanning the frontal hemifield. During the localization task, we recorded the head movements made following stimulus presentation, as a metric for assessing the initial orienting response of the ferrets, as well as the subsequent choice of which target location to approach to receive a reward. Head-orienting responses to auditory-visual stimuli were more accurate and faster than those made to visual but not auditory targets, suggesting that these movements were guided principally by sound alone. In contrast, approach-to-target localization responses were more accurate and faster to spatially congruent auditory-visual stimuli throughout the frontal hemifield than to either visual or auditory stimuli alone. Race model inequality analysis of head-orienting reaction times and approach-to-target response times indicates that different processes, probability summation and neural integration, respectively, are likely to be responsible for the effects of multisensory stimulation on these two measures of localization behaviour. © 2016 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  15. 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

  16. Effect of Helicobacter mustelae infection on ferret gastric epithelial cell proliferation.

    Science.gov (United States)

    Yu, J; Russell, R M; Salomon, R N; Murphy, J C; Palley, L S; Fox, J G

    1995-08-01

    The effect of Helicobacter mustelae infection on gastric epithelial proliferation was studied in ferrets colonized with H.mustelae and specific pathogen-free (SPF) ferrets not infected with H.mustelae. Thirteen H. mustelae-infected ferrets between the ages of 13 and 32 months and 16 SPF ferrets between 6 and 18 months were analyzed. Bacterial cultures, urease tests and Warthin-Starry stains were used to identify H.mustelae. Tissues obtained from the antrum and the body regions of the stomach were assayed by proliferating cell nuclear antigen (PCNA) immunohistochemistry and measured using a computerized color image analysis system. PCNA-expressing gastric epithelia in the antrum and the body regions were significantly increased in the H.mustelae-infected ferrets versus the SPF ferrets (P < 0.001). PCNA positivity in the antrum regions of both the H.mustelae-infected ferrets and SPF ferrets was significantly higher than that of the body regions (P < 0.001). Comparison of the histopathology of infected ferrets indicated that PCNA positivity correlated with the histological severity of gastritis. This study suggests that cell proliferation in ferret gastric mucosa increases with H.mustelae infection and provides evidence that PCNA is a useful biomarker for studying the changes in cell kinetics in the ferret stomach. The data also further support the use of the H.mustelae-infected ferret as an animal model for studying the pathogenesis of Helicobacter pylori-induced gastric diseases of humans.

  17. Importance of lunar and temporal conditions for spotlight surveys of adult black-footed ferrets

    Science.gov (United States)

    Eads, David A.; Jachowski, David S.; Millspaugh, Joshua J.; Biggins, Dean E.

    2012-01-01

    Black-footed ferrets (Mustela nigripes) spend most daylight hours underground in prairie dog (Cynomys) burrows and exhibit aboveground movements primarily at night. Moonlight can influence the activity patterns of ferrets and, consequently, might influence the efficiency of spotlight surveys used by biologists to monitor ferret populations. We related detection of adult ferrets during postbreeding spotlight surveys to lunar and temporal conditions. We most frequently located ferrets during surveys in which the moon breached the horizon. The data suggested intersexual differences in response to moonlight. We located male ferrets most frequently during nights with greater moon illumination, but we did not detect a correlation between moon illumination and spotlight detection of female ferrets. In general, moonlight could facilitate aboveground navigation by ferrets. However, it seems activity under bright moonlight could be costly for female ferrets while they raise young. Detection of ferrets also varied among months. We detected female ferrets most frequently in August–September, when mothers increase hunting efforts to acquire prey for growing offspring (kits). Detection of adult female ferrets declined in October, when kits were likely independent of their mother. We located male ferrets most frequently in September–October, when males might increase activity to monitor female ferrets and male competitors. Consideration of lunar and temporal influences and standardization of postbreeding surveys could enhance site-specific assessment of reintroduction success and across-site assessment of species recoveiy progress. We suggest that postbreeding surveys for ferrets should be enhanced by concentrating efforts in August–September during moonlit nights when the moon is above the horizon.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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...

  3. 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

  4. 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.

  5. Transient diabetes mellitus in a domestic ferret (Mustela putorius furo)

    Science.gov (United States)

    Duhamelle, Alexis; Langlois, Isabelle; Desmarchelier, Marion

    2015-01-01

    A 3.5-year-old spayed female ferret, fed a diet high in refined sugar, was referred for lethargy, polyuria, polydipsia, and polyphagia. Diabetic ketoacidosis was diagnosed. Treatment included insulin therapy and a low carbohydrate diet. Diabetes mellitus resolved 54 d later, and insulin therapy was discontinued. There has been no recurrence of the diabetes mellitus. PMID:26130836

  6. Transient diabetes mellitus in a domestic ferret (Mustela putorius furo)

    OpenAIRE

    Duhamelle, Alexis; Langlois, Isabelle; Desmarchelier, Marion

    2015-01-01

    A 3.5-year-old spayed female ferret, fed a diet high in refined sugar, was referred for lethargy, polyuria, polydipsia, and polyphagia. Diabetic ketoacidosis was diagnosed. Treatment included insulin therapy and a low carbohydrate diet. Diabetes mellitus resolved 54 d later, and insulin therapy was discontinued. There has been no recurrence of the diabetes mellitus.

  7. A new intranasal influenza vaccine based on a novel polycationic lipid-ceramide carbamoyl-spermine (CCS). II. Studies in mice and ferrets and mechanism of adjuvanticity.

    Science.gov (United States)

    Even-Or, Orli; Joseph, Aviva; Itskovitz-Cooper, Noga; Samira, Sarit; Rochlin, Eli; Eliyahu, Hagit; Goldwaser, Itzik; Balasingam, Shobana; Mann, Alex J; Lambkin-Williams, Rob; Kedar, Eli; Barenholz, Yechezkel

    2011-03-16

    We recently showed that lipid assemblies comprised of a novel polycationic sphingolipid (ceramide carbamoyl-spermine, CCS) are an effective adjuvant/carrier when complexed with cholesterol (CCS/C) for influenza and other vaccines administered parenterally and intranasally (i.n.) in mice. Here we expand these studies to ferrets, an established model of influenza infection. We also address the question of why the CCS/C-based liposomal vaccine (also known as VaxiSome™) in mice is superior to vaccines based on liposomes of other lipid compositions (neutral, anionic or cationic). Ferrets immunized i.n. with CCS/C-influenza vaccine produced significantly higher hemagglutination inhibition (HI) antibody titers compared to ferrets immunized intramuscularly with the unadjuvanted influenza vaccine, indicating that the CCS/C-based vaccine is very immunogenic. Furthermore, the i.n. adjuvanted vaccine was shown to significantly reduce the severity of influenza virus infection in ferrets following homologous viral challenge as determined by weight loss, temperature rise and viral titer. No adverse reactions were observed. Pharmacokinetic and biodistribution studies following i.n. administration in mice of CCS/C-based vaccine showed that both the lipids and antigens are retained in the nose and lung for at least 24h, and it appears that this retention correlates with the superior immunogenicity elicited by the adjuvanted vaccine formulation. The CCS lipid also increases production of cytokines (mainly IFN gamma, IL-2 and IL-12) and co-stimulatory molecules' expression, which might further explain the robust adjuvantation of this liposome-based vaccine. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. A comparative analysis of carbon dioxide displacement rates for euthanasia of the ferret.

    Science.gov (United States)

    Fitzhugh, Dawn C; Parmer, Amanda; Shelton, Larry J; Sheets, James T

    2008-02-01

    Though carbon dioxide asphyxiation is a common method of euthanasia for laboratory animals, species-specific guidelines have not been established for this procedure in the domestic ferret (Mustela putorius furo). The authors investigated the efficacy and stress effects of carbon dioxide euthanasia in 24 ferrets that had participated in previous experimental protocols. They euthanized ferrets by placing them in cages that were either prefilled with carbon dioxide or gradually filled at a displacement rate of 10%, 20% or 50% of the cage volume per min. Blinded observers subjectively evaluated ferret distress. Prefilling the cage or filling it at a rate of 50% volume per min resulted in less time to recumbency and to last breath than did filling the cage at a slower displacement rate. Slower carbon dioxide displacement rates also caused an increase in ferret blood glucose concentrations, which may indicate distress. Overall, observers found that prefilling the euthanasia cage caused the least stress to ferrets.

  9. 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.

  10. 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...

  11. Intravenous Immunoglobulin Protects Against Severe Pandemic Influenza Infection

    Directory of Open Access Journals (Sweden)

    Steven Rockman

    2017-05-01

    Full Text Available Influenza is a highly contagious, acute, febrile respiratory infection that can have fatal consequences particularly in individuals with chronic illnesses. Sporadic reports suggest that intravenous immunoglobulin (IVIg may be efficacious in the influenza setting. We investigated the potential of human IVIg to ameliorate influenza infection in ferrets exposed to either the pandemic H1N1/09 virus (pH1N1 or highly pathogenic avian influenza (H5N1. IVIg administered at the time of influenza virus exposure led to a significant reduction in lung viral load following pH1N1 challenge. In the lethal H5N1 model, the majority of animals given IVIg survived challenge in a dose dependent manner. Protection was also afforded by purified F(ab′2 but not Fc fragments derived from IVIg, supporting a specific antibody-mediated mechanism of protection. We conclude that pre-pandemic IVIg can modulate serious influenza infection-associated mortality and morbidity. IVIg could be useful prophylactically in the event of a pandemic to protect vulnerable population groups and in the critical care setting as a first stage intervention.

  12. 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.

  13. Natural and experimental Helicobacter mustelae reinfection following successful antimicrobial eradication in ferrets.

    Science.gov (United States)

    Batchelder, M; Fox, J G; Hayward, A; Yan, L; Shames, B; Murphy, J C; Palley, L

    1996-03-01

    Recrudescence or reinfection may occur after eradication of Helicobacter pylori in humans. We used the ferret Helicobacter mustelae model to investigate the effect of prior infection and eradication on reinfection by experimental and natural routes. Two groups of ferrets with naturally acquired H. mustelae infection were treated with an eradication protocol using amoxicillin, metronidazole, and bismuth subsalicylate. The ferrets were monitored for recrudescence by repeated cultures of endoscopic gastric mucosal biopsies. The ferrets were challenged at 17 months (group I) and 6 months (group II) after eradication with a strain of H. mustelae having a distinctive restriction endonuclease analysis pattern. The eradication protocol was repeated to eliminate the infection produced by experimental challenge. The ferrets were then cohoused intermittently with naturally infected ferrets. The original H. mustelae infection was successfully eliminated by the eradication protocol. No recrudescence was observed in group I for 12 months nor for 3 months in group II after eradication. All ferrets became persistently reinfected with the challenge strain. The infection from the challenge strain was eradicated successfully. No ferrets in group I and all ferrets in group II became infected through cohousing. These results suggest that though prior infection with H. mustelae may confer some protection against reinfection, such protection is not universal in all circumstances; that susceptibility to reinfection by contact with infected animals varies between individuals; and that age may be a factor in this individual variability. These results are applicable to studies of reinfection after eradication of H. pylori in humans.

  14. 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.

  15. 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.

  16. 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.

  17. Energetics of swimming by the ferret: consequences of forelimb paddling.

    Science.gov (United States)

    Fish, Frank E; Baudinette, Russell V

    2008-06-01

    The domestic ferret (Mustela putorius furo) swims by alternate strokes of the forelimbs. This pectoral paddling is rare among semi-aquatic mammals. The energetic implications of swimming by pectoral paddling were examined by kinematic analysis and measurement of oxygen consumption. Ferrets maintained a constant stroke frequency, but increased swimming speed by increasing stroke amplitude. The ratio of swimming velocity to foot stroke velocity was low, indicating a low propulsive efficiency. Metabolic rate increased linearly with increasing speed. The cost of transport decreased with increasing swimming speed to a minimum of 3.59+/-0.28 J N(-1) m(-1) at U=0.44 m s(-1). The minimum cost of transport for the ferret was greater than values for semi-aquatic mammals using hind limb paddling, but lower than the minimum cost of transport for the closely related quadrupedally paddling mink. Differences in energetic performance may be due to the amount of muscle recruited for propulsion and the interrelationship hydrodynamic drag and interference between flow over the body surface and flow induced by propulsive appendages.

  18. Characterization of radiation-induced emesis in the ferret

    International Nuclear Information System (INIS)

    King, G.L.

    1988-01-01

    Forty-eight ferrets (Mustela putorius furo) were individually head-shielded and radiated with bilateral 60 Co gamma radiation at 100 cGy min-1 at doses ranging between 49 and 601 cGy. The emetic threshold was observed at 69 cGy, the ED50 was calculated at 77 cGy, and 100% incidence of emesis occurred at 201 cGy. With increasing doses of radiation, the latency to first emesis after radiation decreased dramatically, whereas the duration of the prodromal period increased. Two other sets of experiments suggest that dopaminergic mechanisms play a minor role in radiation-induced emesis in the ferret. Twenty-two animals were injected either intravenously or subcutaneously with 30 to 300 micrograms/kg of apomorphine. Fewer than 50% of the animals vomited to 300 micrograms/kg apomorphine; central dopaminergic receptor activation was apparent at all doses. Another eight animals received 1 mg/kg domperidone prior to either 201 (n = 4) or 401 (n = 4) cGy radiation and their emetic responses were compared with NaCl-injected-irradiated controls (n = 8). At 201 cGy, domperidone significantly reduced only the total time in emetic behavior. At 401 cGy, domperidone had no salutary effect on radiation-induced emesis. The emetic responses of the ferret to radiation and apomorphine are compared with these responses in other vomiting species

  19. 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.

  20. 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.

  1. INTRAVENOUS IMMUNOGLOBULIN IN PEDIATRIC RHEUMATOLOGY PRACTICE

    Directory of Open Access Journals (Sweden)

    E. I. Alexeeva

    2015-01-01

    Full Text Available Modern successful treatment of rheumatic diseases is impossible without the use of intravenous immunoglobulin. The use of intravenous immunoglobulin is based on strict indications developed as a result of long-term multicenter controlled studies. The article highlights the issues of using immunoglobulin in pediatric rheumatology practice, and provides the review of literature with the results from the evaluation of the efficiency of intravenous immunoglobulin confirming the efficiency of the drug only for certain rheumatic diseases. 

  2. Nature of the endogenous pyrogen (EP) induced by influenza viruses: lack of correlation between EP levels and content of the known pyrogenic cytokines, interleukin 1, interleukin 6 and tumour necrosis factor.

    Science.gov (United States)

    Jakeman, K J; Bird, C R; Thorpe, R; Smith, H; Sweet, C

    1991-03-01

    Fever in influenza results from the release of endogenous pyrogen (EP) following virus-phagocyte interaction and its level correlates with the differing virulence of virus strains. However, the different levels of fever produced in ferrets by intracardial inoculation of EP obtained from the interaction of different virus strains with ferret of human phagocytes did not correlate with the levels of interleukin 1 (IL-1), IL-6 or tumour necrosis factor in the same samples as assayed by conventional in vitro methods. Hence, the EP produced by influenza virus appears to be different to these cytokines.

  3. Immunoglobulin adsorption on modified surfaces

    NARCIS (Netherlands)

    Bremer, M.G.E.G.

    2001-01-01

    Preservation of biological functioning of proteins during immobilisation is of special interest in various biomedical and biotechnical applications. In industry physical adsorption of immunoglobulins (IgGs) onto solid surfaces is still the predominant immobilisation procedure because it is

  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. 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).

  6. Eosinophilic gastroenteritis with Splendore-Hoeppli material in the ferret (Mustela putorius furo).

    Science.gov (United States)

    Fox, J G; Palley, L S; Rose, R

    1992-01-01

    Eosinophilic gastroenteritis, focal or diffuse with eosinophilic infiltrations of the stomach or intestine, has been described in human beings, cats, dogs, and horses. In this paper, we describe infiltration of the gastrointestinal tract with eosinophils accompanied by a circulating eosinophilia in six ferrets (Mustela putorius furo). Clinical signs included chronic weight loss, anorexia, and diarrhea. The small intestines from five ferrets had diffuse infiltrates of eosinophils. This resulted in focal or multifocal loss of the muscular tunic in three ferrets. Two of these ferrets also had eosinophilic gastritis. Eosinophilic granulomas with Splendore-Hoeppli material were present in mesenteric lymph nodes in four ferrets. Two ferrets had multiple organ involvement; one had eosinophilic granulomas in the liver, mesentery, and choroid plexus as well as moderate parapancreatic segmental arteritis with infiltration of eosinophils and mural thrombosis. The second ferret had, in addition to moderate diffuse gastric and small intestinal eosinophilic mucosal infiltrations, interstitial eosinophilic pulmonary infiltrates. Examination of all tissues failed to reveal an infectious agent.

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. Mucosal vaccination with recombinant poxvirus vaccines protects ferrets against symptomatic CDV infection.

    Science.gov (United States)

    Welter, J; Taylor, J; Tartaglia, J; Paoletti, E; Stephensen, C B

    1999-01-28

    Canine distemper virus (CDV) infection of ferrets causes a disease characterized by fever, erythema, conjunctivitis and leukocytopenia, similar clinically to measles except for the fatal neurologic sequelae of CDV. We vaccinated juvenile ferrets twice at 4-week intervals by the intranasal or intraduodenal route with attenuated vaccinia (NYVAC) or canarypox virus (ALVAC) constructs containing the CDV hemagglutinin and fusion genes. Controls were vaccinated with the same vectors expressing rabies glycoprotein. Animals were challenged intranasally 4 weeks after the second vaccination with virulent CDV. Body weights, white blood cell (WBC) counts and temperatures were monitored and ferrets were observed daily for clinical signs of infection. WBCs were assayed for the presence of viral RNA by RT-PCR. Intranasally vaccinated animals survived challenge with no virologic or clinical evidence of infection. Vaccination by the intraduodenal route did not provide complete protection. All control animals developed typical distemper. Ferrets can be effectively protected against distemper by mucosal vaccination with poxvirus vaccines.

  16. 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...

  17. Cytokines as endogenous pyrogens.

    Science.gov (United States)

    Dinarello, C A

    1999-03-01

    Cytokines are pleiotropic molecules mediating several pathologic processes. Long before the discovery of cytokines as immune system growth factors or as bone marrow stimulants, investigators learned a great deal about cytokines when they studied them as the endogenous mediators of fever. The terms "granulocytic" or "endogenous pyrogen" were used to describe substances with the biologic property of fever induction. Today, we recognize that pyrogenicity is a fundamental biologic property of several cytokines and hence the clinically recognizeable property of fever links host perturbations during disease with fundamental perturbations in cell biology. In this review, the discoveries made on endogenous pyrogens are revisited, with insights into the importance of the earlier work to the present-day understanding of cytokines in health and in disease.

  18. 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.

  19. 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.

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

    OpenAIRE

    L. Pavlačík; V. Celer, Jr.; V. Kajerová; V. Jekl; Z. Knotek; I. Literák

    2007-01-01

    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 vac...

  1. 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.

  2. Hybridization and the phylogenetic relationship between polecats and domestic ferrets in Britain

    Science.gov (United States)

    Davison, A.; Birks, J. D. S.; Griffiths, H. I.; Kitchener, A. C.; Biggins, D.; Butlin, R. K.

    1999-01-01

    Ferrets (Mustela furo) were domesticated from polecats (M. putorius, M. eversmannii) over 2000 years ago. Following their introduction to Britain, they escaped and hybridized with native European polecats (M. putorius). Native polecats declined to the point of near extinction prior to World War I, but have recently begun to expand from a Welsh refugium. Concern has arisen as to the extent of polecat/ferret introgression, and in particular, whether the expanding population is of mainly hybrid origin. Therefore, mitochondrial DNA sequencing was used to investigate polecat genetic diversity in Britain. Two geographically distinct lineages were found, where one may be ancestral to the British polecat, and the other to the domestic ferret. The ancestral distribution of each lineage, or assortative mating is sufficient to explain the observed pattern. A further comparison between the distribution of the polecat phenotype and mitochondrial haplotype implies that the current population expansion may be mediated by dispersing male polecats hybridizing with female feral ferrets. However, the wild source of the ferret remains obscure. Relatively recent speciation from European mink (M. lutreola) and black-footed ferrets (M. nigripes), and/or the effects of hybridization result in an unresolved molecular phylogeny.

  3. Serologic evaluation, efficacy, and safety of a commerical modified-live canine distemper vaccine in domestic ferrets.

    Science.gov (United States)

    Wimsatt, J; Jay, M T; Innes, K E; Jessen, M; Collins, J K

    2001-05-01

    To determine efficacy and safety of a commercial modified-live canine distemper virus (CDV) vaccine used for prophylaxis in domestic ferrets. Sixteen 16-week-old neutered male ferrets. Equal groups of ferrets were inoculated subcutaneously at 16 and 20 weeks of age with saline (0.9% NaCl) solution or a vaccine derived from the Onderstepoort CDV strain and attenuated in a primate cell line. Live virulent CDV was administered to all ferrets intranasally and orally 3 weeks after the second inoculation. Clinical signs and body weights were monitored regularly during the study. Blood samples for serologic examination were drawn prior to each inoculation, before challenge exposure, and 10, 15, and 21 days after exposure. Blood samples for reverse transcriptase polymerase chain reaction (RT-PCR) were obtained 5 days after the first vaccination, and 5, 10, 15, and 21 days after challenge exposure. After challenge exposure, control ferrets had significantly more clinical signs and weight loss, compared with vaccinates. All vaccinated ferrets survived, whereas all control ferrets died. The RT-PCR assay was successful in detecting CDV in blood and fresh or formalin-fixed tissues from infected ferrets. Findings suggest that the vaccine when given SC to domestic ferrets as directed is safe and protective against challenge exposure with virulent CDV. The RT-PCR assay may simplify detection of CDV in fresh and fixed tissues.

  4. 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.

  5. 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.

  6. Cytokines and Liver Diseases

    Directory of Open Access Journals (Sweden)

    Herbert Tilg

    2001-01-01

    Full Text Available Cytokines are pleiotropic peptides produced by virtually every nucleated cell in the body. In most tissues, including the liver, constitutive production of cytokines is absent or minimal. There is increasing evidence that several cytokines mediate hepatic inflammation, apoptosis and necrosis of liver cells, cholestasis and fibrosis. Interestingly, the same mediators also mediate the regeneration of liver tissue after injury. Among the various cytokines, the proinflammatory cytokine tumour necrosis factor-alpha (TNF-a has emerged as a key factor in various aspects of liver disease, such as cachexia and/or cholestasis. Thus, antagonism of TNF-a and other injury-related cytokines in liver diseases merits evaluation as a treatment of these diseases. However, because the same cytokines are also necessary for the regeneration of the tissue after the liver has been injured, inhibition of these mediators might impair hepatic recovery. The near future will bring the exiting clinical challenge of testing new anticytokine strategies in various liver diseases.

  7. Diabetes mellitus in a black-footed ferret

    Science.gov (United States)

    Carpenter, J.W.; Novilla, M.N.

    1977-01-01

    Diabetes mellitus was tentatively diagnosed in a black-footed ferret with polyuria, polydipsia, polyphagia, dehydration, and weight loss. Laboratory findings (marked hyperglycemia (724 mg/100 ml), glycosuria, and ketonuria) and the subsequent favorable response to insulin therapy confirmed the diagnosis. Although lesions were not observed in the pancreas, gross and histologic findings concomitant with diabetes mellitus included arteriosclerosis, with calcification of the aorta and other major vessels; mild necrotizing hepatitis; and mild proliferative glomerulonephritis. A perineal adenocarcinoma, with metastasis to an internal iliac lymph node, was an incidental finding. Special stains demonstrated adequate numbers of beta cell granules in the islets of Langerhans. Thus, the diabetes was apparently due to a lack of release of the synthesized insulin or to diminished effectiveness of the secreted insulin.

  8. 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.)

  9. 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 E.

    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

  10. 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......, IL-6 and tumour necrosis factor (TNF)-alpha were examined, using ELISA assays, in culture supernatants of human peripheral blood leucocytes infected with influenza virus and subsequently incubated with endotoxin. Levels of TNF-alpha were increased compared to cells incubated with virus or endotoxin...... alone. Levels of IL-1 beta were also increased whereas levels of IL-6 were generally not enhanced. Cytokines appeared within 1-2 h of stimulation with virus or endotoxin and increased subsequently to reach maximum titres between 16 and 20 h post treatment. While levels of cytokine were much lower when...

  11. Cytokines in bipolar disorder

    DEFF Research Database (Denmark)

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

    2012-01-01

    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...... 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...

  12. 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....

  13. Involvement of the different lung compartments in the pathogenesis of pH1N1 influenza virus infection in ferrets.

    Science.gov (United States)

    Vidaña, Beatriz; Martínez, Jorge; Martorell, Jaime; Montoya, María; Córdoba, Lorena; Pérez, Mónica; Majó, Natàlia

    2016-11-08

    Severe cases after pH1N1 infection are consequence of interstitial pneumonia triggered by alveolar viral replication and an exacerbated host immune response, characterized by the up-regulation of pro-inflammatory cytokines and the influx of inflammatory leukocytes to the lungs. Different lung cell populations have been suggested as culprits in the unregulated innate immune responses observed in these cases. This study aims to clarify this question by studying the different induction of innate immune molecules by the distinct lung anatomic compartments (vascular, alveolar and bronchiolar) of ferrets intratracheally infected with a human pH1N1 viral isolate, by means of laser microdissection techniques. The obtained results were then analysed in relation to viral quantification in the different anatomic areas and the histopathological lesions observed. More severe lung lesions were observed at 24 h post infection (hpi) correlating with viral antigen detection in bronchiolar and alveolar epithelial cells. However, high levels of viral RNA were detected in all anatomic compartments throughout infection. Bronchiolar areas were the first source of IFN-α and most pro-inflammatory cytokines, through the activation of RIG-I. In contrast, vascular areas contributed with the highest induction of CCL2 and other pro-inflammatory cytokines, through the activation of TLR3.

  14. 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.

  15. Use of intravenous immunoglobulins in clinical practice

    Directory of Open Access Journals (Sweden)

    E.K. Donyush

    2011-01-01

    Full Text Available Immunoglobulins are main component of immune defense; they take part in anti-infectious resistance of organism and regulate processes of different immune reactions. Intravenous immunoglobulins are the most frequently used products made from donor blood plasma. The need in these drugs is steadily increasing during last 15–20 years, and indications are widening due to modern hightechnology methods of production and cleaning. The article presents modern data on formula, mechanisms of action and indications for different groups of intravenous immunoglobulins (standard, hyperimmune, fortified and description of possible adverse events.Key words: immuglobulines, prophylaxis, treatment, unfavorable reaction, children.

  16. 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.

  17. 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...

  18. Populations of Radial Glial Cells Respond Differently to Reelin and Neuregulin1 in a Ferret Model of Cortical Dysplasia

    Science.gov (United States)

    2010-10-28

    postnatally [11,12,13,14,15]. Ferrets are also the smallest mammals with a convoluted cortex [16]. Proliferation of intermediate progenitor cells in ferrets...24th day of development (E24) disrupts early cortical development, resulting in a thin and poorly laminated cortex, where neurons migrating radially and

  19. 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.

  20. Emesis, radiation exposure, and local cerebral blood flow in the ferret

    International Nuclear Information System (INIS)

    Tuor, U.I.; Kondysar, M.H.; Harding, R.K.

    1988-01-01

    We examined the sensitivity of the ferret to emetic stimuli and the effect of radiation exposure near the time of emesis on local cerebral blood flow. Ferrets vomited following the administration of either apomorphine (approx 45% of the ferrets tested) or peptide YY (approx 36% of those tested). Exposure to radiation was a very potent emetic stimulus, but vomiting could be prevented by restraint of the hindquarters of the ferret. Local cerebral blood flow was measured using a quantitative autoradiographic technique and with the exception of several regions in the telencephalon and cerebellum, local cerebral blood flow in the ferret was similar to that in the rat. In animals with whole-body exposure to moderate levels of radiation (4 Gy of 137 Cs), mean arterial blood pressure was similar to that in the control group. However, 15-25 min following irradiation there was a general reduction of local cerebral blood flow ranging from 7 to 33% of that in control animals. These cerebral blood flow changes likely correspond to a reduced activation of the central nervous system

  1. Transcription factor GATA-4 is a marker of anaplasia in adrenocortical neoplasms of the domestic ferret (Mustela putorius furo).

    Science.gov (United States)

    Peterson, R A; Kiupel, M; Bielinska, M; Kiiveri, S; Heikinheimo, M; Capen, C C; Wilson, D B

    2004-07-01

    Adrenocortical neoplasms are a common cause of morbidity in neutered ferrets. Recently we showed that gonadectomized DBA/2J mice develop adrenocortical tumors that express transcription factor GATA-4. Therefore, we screened archival specimens of adrenocortical neoplasms from neutered ferrets to determine whether GATA-4 could be used as a tumor marker in this species. Nuclear immunoreactivity for GATA-4 was evident in 19/22 (86%) of ferret adrenocortical carcinomas and was prominent in areas exhibiting myxoid differentiation. Normal adrenocortical cells lacked GATA-4 expression. Two other markers of adrenocortical tumors in gonadectomized mice, inhibin-alpha and luteinizing hormone receptor, were coexpressed with GATA-4 in some of the ferret tumors. No GATA-4 expression was observed in three cases of nodular hyperplasia, but patches of anaplastic cells expressing GATA-4 were evident in 7/14 (50%) of tumors classified as adenomas. We conclude that GATA-4 can function as a marker of anaplasia in ferret adrenocortical tumors.

  2. 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.

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

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. Cytokine loops driving senescence

    Czech Academy of Sciences Publication Activity Database

    Bartek, Jiří; Hodný, Zdeněk; Lukáš, Jan

    2008-01-01

    Roč. 10, č. 8 (2008), s. 887-889 ISSN 1465-7392 Institutional research plan: CEZ:AV0Z50520514 Keywords : cellular senescence * cytokines * autocrine feedback loop Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 17.774, year: 2008

  9. 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.

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

    Science.gov (United States)

    Britton, Ann P; Dubey, J P; Rosenthal, Benjamin M

    2010-04-19

    Naturally occurring Sarcocystis neurona infection in a ferret (Mustela putorius furo) 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 by staining with S. neurona-specific antibodies, and by phylogenetic analyses of conserved and variable portions of nuclear ribosomal DNA. On the basis of intense schizogony in the nasal mucosa, we propose the possibility of an olfactory nerve pathway route of infection for S. neurona meningoencephalitis.

  11. Vestibular syndrome due to a choroid plexus papilloma in a ferret.

    Science.gov (United States)

    van Zeeland, Yvonne; Schoemaker, Nico; Passon-Vastenburg, Maartje; Kik, Marja

    2009-01-01

    A 6-year-old, castrated male ferret (Mustela putorius furo) was presented with progressive neurological signs consisting of a right-sided head tilt and ataxia. Neurological examination revealed hemiparesis and absence of proprioception on the right side, consistent with central vestibular syndrome. Measurement of blood glucose excluded hypoglycemia due to insulinoma. Contrast-enhanced computed tomography revealed the presence of an intracranial mass, consistent with either granuloma or neoplasia. Palliative treatment with prednisolone yielded no improvement. At postmortem examination, a final diagnosis of a choroid plexus papilloma originating from the fourth ventricle was made. This is the first report of such a tumor in a ferret.

  12. Ferrets Infected with Bundibugyo Virus or Ebola Virus Recapitulate Important Aspects of Human Filovirus Disease.

    Science.gov (United States)

    Kozak, Robert; He, Shihua; Kroeker, Andrea; de La Vega, Marc-Antoine; Audet, Jonathan; Wong, Gary; Urfano, Chantel; Antonation, Kym; Embury-Hyatt, Carissa; Kobinger, Gary P; Qiu, Xiangguo

    2016-10-15

    Bundibugyo virus (BDBV) is the etiological agent of a severe hemorrhagic fever in humans with a case-fatality rate ranging from 25 to 36%. Despite having been known to the scientific and medical communities for almost 1 decade, there is a dearth of studies on this pathogen due to the lack of a small animal model. Domestic ferrets are commonly used to study other RNA viruses, including members of the order Mononegavirales To investigate whether ferrets were susceptible to filovirus infections, ferrets were challenged with a clinical isolate of BDBV. Animals became viremic within 4 days and succumbed to infection between 8 and 9 days, and a petechial rash was observed with moribund ferrets. Furthermore, several hallmarks of human filoviral disease were recapitulated in the ferret model, including substantial decreases in lymphocyte and platelet counts and dysregulation of key biochemical markers related to hepatic/renal function, as well as coagulation abnormalities. Virological, histopathological, and immunohistochemical analyses confirmed uncontrolled BDBV replication in the major organs. Ferrets were also infected with Ebola virus (EBOV) to confirm their susceptibility to another filovirus species and to potentially establish a virus transmission model. Similar to what was seen with BDBV, important hallmarks of human filoviral disease were observed in EBOV-infected ferrets. This study demonstrates the potential of this small animal model for studying BDBV and EBOV using wild-type isolates and will accelerate efforts to understand filovirus pathogenesis and transmission as well as the development of specific vaccines and antivirals. The 2013-2016 outbreak of Ebola virus in West Africa has highlighted the threat posed by filoviruses to global public health. Bundibugyo virus (BDBV) is a member of the genus Ebolavirus and has caused outbreaks in the past but is relatively understudied, likely due to the lack of a suitable small animal model. Such a model for BDBV is

  13. 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.

  14. 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

  15. 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).

  16. 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

  17. 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.

  18. Host gene expression profiles in ferrets infected with genetically distinct henipavirus strains

    NARCIS (Netherlands)

    Leon, A.J. (Alberto J.); Borisevich, V. (Viktoriya); Boroumand, N. (Nahal); Seymour, R. (Robert); Nusbaum, R. (Rebecca); Escaffre, O. (Olivier); Xu, L. (Luoling); Kelvin, D.J. (David J.); B. Rockx (Barry)

    2018-01-01

    textabstractHenipavirus infection causes severe respiratory and neurological disease in humans that can be fatal. To characterize the pathogenic mechanisms of henipavirus infection in vivo, we performed experimental infections in ferrets followed by genome-wide gene expression analysis of lung and

  19. 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 ...

  20. Progress toward generating a ferret model of cystic fibrosis by somatic cell nuclear transfer

    Directory of Open Access Journals (Sweden)

    Engelhardt John F

    2003-11-01

    Full Text Available Abstract Mammalian cloning by nuclear transfer from somatic cells has created new opportunities to generate animal models of genetic diseases in species other than mice. Although genetic mouse models play a critical role in basic and applied research for numerous diseases, often mouse models do not adequately reproduce the human disease phenotype. Cystic fibrosis (CF is one such disease. Targeted ablation of the cystic fibrosis transmembrane conductance regulator (CFTR gene in mice does not adequately replicate spontaneous bacterial infections observed in the human CF lung. Hence, several laboratories are pursuing alternative animal models of CF in larger species such as the pig, sheep, rabbits, and ferrets. Our laboratory has focused on developing the ferret as a CF animal model. Over the past few years, we have investigated several experimental parameters required for gene targeting and nuclear transfer (NT cloning in the ferret using somatic cells. In this review, we will discuss our progress and the hurdles to NT cloning and gene-targeting that accompany efforts to generate animal models of genetic diseases in species such as the ferret.

  1. Extreme Tetralogy of Fallot With Polycythemia in a Ferret (Mustela putorius furo).

    Science.gov (United States)

    Dias, Sara; Planellas, Marta; Canturri, Albert; Martorell, Jaume

    2017-06-01

    A 5-month-old, intact male ferret (Mustela putorius furo) was presented with apathy, tachypnea and exercise intolerance. On initial physical examination, tachypnea and cyanosis were the two primary clinical signs detected. The complete blood count also revealed a severe polycythemia, with lymphopenia, neutrophilia and eosinophilia. Further diagnostic imaging tests were performed. The thoracic radiographs revealed cardiomegaly and a diffuse alveolar pulmonary pattern. Consequently, an echocardiography was performed and showed an interventricular septal defect, pulmonic artery occlusion, overriding of the aorta and right ventricle hypertrophy. All abnormalities were compatible with a tetralogy of Fallot (TOF). As a treatment plan, a phlebotomy was performed and the ferret was posteriorly maintained with oxygen and fluid therapy. The following day, the hematocrit decreased 11% and the respiratory distress improved. Four days later, the ferret got clinically worse and was euthanized. A necropsy was performed and confirmed the presence of an extreme TOF with a diffused interstitial pneumonia secondary to Pneumocystis carinii. To the author's knowledge, this is the first report of an extreme tetralogy of Fallot with polycythemia in a ferret. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Defining the sizes of airborne particles that mediate influenza transmission in ferrets.

    Science.gov (United States)

    Zhou, Jie; Wei, Jianjian; Choy, Ka-Tim; Sia, Sin Fun; Rowlands, Dewi K; Yu, Dan; Wu, Chung-Yi; Lindsley, William G; Cowling, Benjamin J; McDevitt, James; Peiris, Malik; Li, Yuguo; Yen, Hui-Ling

    2018-03-06

    Epidemics and pandemics of influenza are characterized by rapid global spread mediated by non-mutually exclusive transmission modes. The relative significance between contact, droplet, and airborne transmission is yet to be defined, a knowledge gap for implementing evidence-based infection control measures. We devised a transmission chamber that separates virus-laden particles by size and determined the particle sizes mediating transmission of influenza among ferrets through the air. Ferret-to-ferret transmission was mediated by airborne particles larger than 1.5 µm, consistent with the quantity and size of virus-laden particles released by the donors. Onward transmission by donors was most efficient before fever onset and may continue for 5 days after inoculation. Multiple virus gene segments enhanced the transmissibility of a swine influenza virus among ferrets by increasing the release of virus-laden particles into the air. We provide direct experimental evidence of influenza transmission via droplets and fine droplet nuclei, albeit at different efficiency. Copyright © 2018 the Author(s). Published by PNAS.

  3. 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...

  4. 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.

  5. 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.

  6. 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.

  7. Censored correlated cytokine concentrations

    DEFF Research Database (Denmark)

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

    2013-01-01

    ) can be used to describe the relative concentration between two cytokines, and the GMR ratio (GMRR) can be used to compare two groups. The problem is how to estimate GMRRs from censored distributions.We evaluated methods, including simple deletion and substitution, in simulated and real data. One...... 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...

  8. 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.

  9. Proceedings of the symposium on the management of prairie dog complexes for the reintroduction of the black-footed ferret

    Science.gov (United States)

    Oldemeyer, John L.; Biggins, Dean E.; Miller, Brian J.; Crete, Ronald

    1993-01-01

    The workshop featured a review of current knowledge in the biology of prairie dogs in the context of managing black-footed ferret habitat. The review addressed two main components. The first consisted of a series of papers on prairie dog habitat and biology. The second component of the workshop was a summary of the participants' discussion about managing prairie dog complexes. This discussion was based on the previously identified papers and profited from the participants' expertise on the ecology of black-footed ferrets and prairie dogs. The report provides current and comprehensive information about management of habitat for prairie dogs and black-footed ferrets and is a useful guide for agencies and individuals that manage black-footed ferrets.

  10. 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.

  11. 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.

  12. 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...

  13. 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

  14. The Immunobiology of Immunoglobulin G4

    NARCIS (Netherlands)

    Lighaam, Laura C.; Rispens, Theo

    2016-01-01

    Human immunoglobulin G4 (IgG4) antibodies are in many ways unusual. In this review, an overview is given of the structural and functional aspects of IgG4 antibodies, the consequences of IgG4 antibody formation in various disease settings, and the factors involved in the regulation of IgG4 responses.

  15. 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

  16. [Production, specificity and structure of immunoglobulins].

    Science.gov (United States)

    Goujard, C; Delfraissy, J F

    1991-03-21

    Immunoglobulin is a key factor of the immune response resulting from B-cell activation and associated with T-cell stimulation. Because of its structure, this antibody has a dual function: it specifically recognizes the inducer antigen in the variable region and eliminates it by a constant portion which is responsible for effector properties. Surface immunoglobulin, therefore, is the B-cell antigen receptor; it differs from the T-cell receptor in that it recognizes the antigen unbound to the major istocompatibility complex; binding the antigen results in direct signal transduction first in the cytoplasm, then in the nucleus. This receptor can be secreted in the body: it is made up of circulating immunoglobulins. Human immunoglobulins are divided into 5 classes, each of them with its own response kinetics, distribution and functions. The variability of the antibody response accounts for a genetic organization involving numerous genes which may be associated with each other, or mutate, or recombine during maturation of the lymphocytes. Altogether, this system has a theoretical capacity of response to three hundred million different antigens.

  17. 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.

  18. 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.

  19. 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 ...

  20. 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...

  1. 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 difficul...

  2. Cytokines and uveitis, a review

    NARCIS (Netherlands)

    de Vos, A. F.; Hoekzema, R.; Kijlstra, A.

    1992-01-01

    Although the exact pathogenic mechanisms underlying uveitis are unknown, cytokines appear to be involved in this inflammatory disorder. This review describes the studies in which the uveitogenic properties of several cytokines, including tumor necrosis factor (TNF), interleukin 1 (IL-1), IL-6, IL-8

  3. Challenges to reestablishment of free-ranging populations of black-footed ferrets

    Science.gov (United States)

    Biggins, D.E.; Godbey, J.L.

    2003-01-01

    The black-footed ferret (Mustela nigripes) of North America is critically endangered due in part to its extreme specialization on formerly stable and abundant prairie dogs (Cynomys). Its close relative, the Siberian polecat (M. eversmannii) seems to have been subjected to a varying environment that was not conducive to specialization. One source of environmental variation in Asian steppes was plague (caused by Yersina pestis), which was absent from North America. Introduction of plague to North America presents serious challenges to ferret recovery. Partial solutions to other biological and political problems have been found, resulting in improved production in captivity, increased survival post-release, and thriving populations in plague-free South Dakota.

  4. Intravenous immunoglobulin and Alzheimer's disease immunotherapy.

    Science.gov (United States)

    Solomon, Beka

    2007-02-01

    Amyloid-beta peptide (Abeta) contributes to the acute progression of Alzheimer's disease (AD) and has become the main target for therapeutics. Active immunization with Abeta in individuals with AD has been efficacious; however, some patients developed side effects, possibly related to an autoimmune response. Evidence that intravenous immunoglobulin (IVIg), an FDA-approved purified immunoglobulin fraction from normal human donor blood, shows promise of passive immunotherapy for AD is reviewed. Investigations into the molecular effects of IVIg on Abeta clearance, using the BV-2 cellular microglia line, demonstrate that IVIg dissolves Abeta fibrils in vitro, increases cellular tolerance to Abeta, enhances microglial migration toward Abeta deposits, and mediates phagocytosis of Abeta. Preliminary clinical results indicate that IVIg, which contains natural antibodies against the Abeta, warrants further study into its potential to deliver a controlled immune attack on the peptide, avoiding the immune toxicities that have had a negative impact on the first clinical trials of vaccine against Abeta.

  5. Persistent production of TH2-type cytokines and polyclonal B cell activation after chronic administration of staphylococcal enterotoxin B in mice

    NARCIS (Netherlands)

    Florquin, S.; Amraoui, Z.; Goldman, M.

    1996-01-01

    In order to study the immunopathological consequences of repeated exposure to bacterial superantigens, we evaluated the production of cytokines, the profile of serum immunoglobulins and the tissue damage in BALB/c mice injected twice a week for 3 weeks with 50 micrograms of staphylococcal

  6. Neuromyelitis Optica Immunoglobulin G in a Child

    OpenAIRE

    Hudson, Lynsee A.; Bernard, Timothy J.; Tseng, Brian S.; Miller, Bradford R.; Corboy, John R.

    2006-01-01

    Neuromyelitis optica or Devic’s syndrome is an uncommon demyelinating disorder that preferentially attacks the spinal cord and optic nerves. Although it is well described in adults, childhood neuromyelitis optica has rarely been reported in the literature and is frequently misdiagnosed as severe multiple sclerosis. Recently, a serum immunoglobulin G test for neuromyelitis optica has become available which may clarify and accelerate the diagnosis. This report describes a child with recurrent m...

  7. 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.

  8. 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

  9. 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.

  10. Anatomical and Physiological Characteristics of the Ferret Lateral Rectus Muscle and Abducena Nucleus

    Science.gov (United States)

    2007-01-25

    from the ferret LR Slow Resistant group is larger than the typically powerful Fast Fatigable motor units in the cat. Whole Muscle Contractile...623-632, 1990. 21. HESS A and PILAR G. SLOW FIBRES IN THE EXTRAOCULAR MUSCLES OF THE CAT. J Physiol 169: 780-798, 1963. 22. Jacoby J, Chiarandini DJ...were split between the LR and retractor bulbi (RB) muscle slips. In addition to individual motor units, the whole LR muscle was evaluated for twitch

  11. Dorso-Lateral Frontal Cortex of the Ferret Encodes Perceptual Difficulty during Visual Discrimination

    OpenAIRE

    Zhe Charles Zhou; Chunxiu Yu; Kristin K. Sellers; Flavio Fröhlich

    2016-01-01

    Visual discrimination requires sensory processing followed by a perceptual decision. Despite a growing understanding of visual areas in this behavior, it is unclear what role top-down signals from prefrontal cortex play, in particular as a function of perceptual difficulty. To address this gap, we investigated how neurons in dorso-lateral frontal cortex (dl-FC) of freely-moving ferrets encode task variables in a two-alternative forced choice visual discrimination task with high- and low-contr...

  12. Promotion of ulcerative duodenitis in young ferrets by oral immunization with Helicobacter mustelae and muramyl dipeptide.

    Science.gov (United States)

    Whary, M T; Palley, L S; Batchelder, M; Murphy, J C; Yan, L; Taylor, N S; Fox, J G

    1997-06-01

    The purpose of this study was to determine whether oral immunization of ferret kits with a whole-cell sonicate of Helicobacter mustelae lysate (Hml) and the adjuvant muramyl dipeptide (MDP) would reduce the incidence of natural colonization with H. mustelae and the extent of Helicobacter-associated gastritis by enhancing the host mucosal immune response. Between the ages of 4 and 11 weeks, 44 ferret kits were gavaged with Hml and various doses of MDP. The extent of gastritis and duodenitis and the immune response to H. mustelae were evaluated. All kits became colonized naturally with H. mustelae and the majority developed mild to severe gastritis and duodenitis. Kits that received Hml with MDP developed significantly greater inflammation of the gastric antrum and duodenum, as compared to kits vaccinated with Hml alone. Vaccination with Hml and 50 micrograms of MDP was associated with severe lesions in the proximal duodenum characterized by accumulation of mononuclear inflammatory cells, mucosal erosion, and ulceration. Although serum antibody specific for H. mustelae in 4-week-old kits was approximately 50% of adult levels, a finding attributable to passively acquired maternal antibody, both systemic and mucosal antibody levels became depressed over time despite oral vaccination. The humoral immune response was sufficiently low to prevent detection of any significant dose effect of MDP on antibody levels among experimental groups. Oral vaccination of young ferrets with Hml and 50 micrograms MDP increased the risk of Helicobacter-associated mucosal ulceration in the proximal duodenum, which was associated with low humoral (but significant cell-mediated) immune responses to H. mustelae. In retrospect, the frequency of vaccination may have suppressed the systemic humoral immune response, thereby promoting mucosal damage by H. mustelae. The 50-microgram dose of MDP enhanced the cell-mediated immune response, which indirectly contributed to development of severe lesions

  13. 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.

  14. Prolonged influenza virus shedding and emergence of antiviral resistance in immunocompromised patients and ferrets.

    Directory of Open Access Journals (Sweden)

    Erhard van der Vries

    Full Text Available Immunocompromised individuals tend to suffer from influenza longer with more serious complications than otherwise healthy patients. Little is known about the impact of prolonged infection and the efficacy of antiviral therapy in these patients. Among all 189 influenza A virus infected immunocompromised patients admitted to ErasmusMC, 71 were hospitalized, since the start of the 2009 H1N1 pandemic. We identified 11 (15% cases with prolonged 2009 pandemic virus replication (longer than 14 days, despite antiviral therapy. In 5 out of these 11 (45% cases oseltamivir resistant H275Y viruses emerged. Given the inherent difficulties in studying antiviral efficacy in immunocompromised patients, we have infected immunocompromised ferrets with either wild-type, or oseltamivir-resistant (H275Y 2009 pandemic virus. All ferrets showed prolonged virus shedding. In wild-type virus infected animals treated with oseltamivir, H275Y resistant variants emerged within a week after infection. Unexpectedly, oseltamivir therapy still proved to be partially protective in animals infected with resistant virus. Immunocompromised ferrets offer an attractive alternative to study efficacy of novel antiviral therapies.

  15. Transmission of Human Respiratory Syncytial Virus in the Immunocompromised Ferret Model

    Science.gov (United States)

    de Waal, Leon; Smits, Saskia L.; Veldhuis Kroeze, Edwin J. B.; van Amerongen, Geert; Pohl, Marie O.; Osterhaus, Albert D. M. E.; Stittelaar, Koert J.

    2018-01-01

    Human respiratory syncytial virus (HRSV) causes substantial morbidity and mortality in vulnerable patients, such as the very young, the elderly, and immunocompromised individuals of any age. Nosocomial transmission of HRSV remains a serious challenge in hospital settings, with intervention strategies largely limited to infection control measures, including isolation of cases, high standards of hand hygiene, cohort nursing, and use of personal protective equipment. No vaccines against HRSV are currently available, and treatment options are largely supportive care and expensive monoclonal antibody or antiviral therapy. The limitations of current animal models for HRSV infection impede the development of new preventive and therapeutic agents, and the assessment of their potential for limiting HRSV transmission, in particular in nosocomial settings. Here, we demonstrate the efficient transmission of HRSV from immunocompromised ferrets to both immunocompromised and immunocompetent contact ferrets, with pathological findings reproducing HRSV pathology in humans. The immunocompromised ferret-HRSV model represents a novel tool for the evaluation of intervention strategies against nosocomial transmission of HRSV. PMID:29301313

  16. 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.

  17. Diagnosis and Management of Polycythemia Vera in a Ferret (Mustela putorius furo).

    Science.gov (United States)

    Le, Kim; Beaufrère, Hugues; Bassel, Laura L; Wills, Sarah; Laniesse, Delphine; Blois, Shauna L; Smith, Dale A

    2016-12-01

    A 5-y-old female ferret (Mustela putorius furo) was evaluated for diarrhea, anorexia, and lethargy for 1 wk. Only mild dehydration was detected on physical examination. CBC analysis revealed marked erythrocytosis with an unremarkable plasma biochemistry panel; follow-up CBC analyses revealed a consistent primary erythrocytosis. Whole-body radiographs and abdominal ultrasonography were unremarkable except for a small nephrolith in the right kidney and a small cyst in the left kidney. The plasma erythropoietin level was 17.0 mIU/mL and considered normal. In light of the diagnostic work-up and consistent erythrocytosis, a diagnosis of polycythemia vera (primary erythrocytosis) was made. The initial presentation of diarrhea resolved after treatment with oral metronidazole (20 mg/kg PO BID for 7 d). Treatment for the polycythemia consisted of a phlebotomy initially followed by chemotherapy with hydroxyurea (10 mg/kg PO BID). During the subsequent 12 mo, the hydroxyurea dose adjusted according to follow-up CBC results, and finding an optimal dosage regimen proved to be challenging. One year after the initial diagnosis, the ferret presented to an emergency clinic for acute and severe hemorrhagic diarrhea and died shortly thereafter. The postmortem diagnosis was acute venous infarction of the small and large intestine. To our knowledge, this report is the first to describe the diagnosis and long-term management of polycythemia vera in a ferret and the use of hydroxyurea for this purpose.

  18. Development of chronic colitis is dependent on the cytokine MIF.

    Science.gov (United States)

    de Jong, Y P; Abadia-Molina, A C; Satoskar, A R; Clarke, K; Rietdijk, S T; Faubion, W A; Mizoguchi, E; Metz, C N; Alsahli, M; ten Hove, T; Keates, A C; Lubetsky, J B; Farrell, R J; Michetti, P; van Deventer, S J; Lolis, E; David, J R; Bhan, A K; Terhorst, C; Sahli, M A

    2001-11-01

    The cytokine macrophage-migration inhibitory factor (MIF) is secreted by a number of cell types upon induction by lipopolysaccharide (LPS). Because colitis is dependent on interplay between the mucosal immune system and intestinal bacteria, we investigated the role of MIF in experimental colitis. MIF-deficient mice failed to develop disease, but reconstitution of MIF-deficient mice with wild-type innate immune cells restored colitis. In addition, established colitis could be treated with anti-MIF immunoglobulins. Thus, murine colitis is dependent on continuous MIF production by the innate immune system. Because we found increased plasma MIF concentrations in patients with Crohn's disease, these data suggested that MIF is a new target for intervention in Crohn's disease.

  19. Relationship between vomiting and taste aversion learning in the ferret: studies with ionizing radiation, lithium chloride, and amphetamine.

    Science.gov (United States)

    Rabin, B M; Hunt, W A

    1992-09-01

    The relationship between emesis and taste aversion learning was studied in ferrets (Mustela putorius furo) following exposure to ionizing radiation (50-200 cGy) or injection of lithium chloride (1.5-3.0 mEq/kg, ip). When 10% sucrose or 0.1% saccharin was used as the conditioned stimulus, neither unconditioned stimulus produced a taste aversion, even when vomiting was produced by the stimulus (Experiments 1 and 2). When a canned cat food was used as the conditioned stimulus, lithium chloride, but not ionizing radiation, produced a taste aversion (Experiment 3). Lithium chloride was effective in producing a conditioned taste aversion when administration of the toxin was delayed by up to 90 min following the ingestion of the canned cat food, indicating that the ferrets are capable of showing long-delay learning (Experiment 4). Experiment 5 examined the capacity of amphetamine, which is a qualitatively different stimulus than lithium chloride or ionizing radiation, to produce taste aversion learning in rats and cats as well as in ferrets. Injection of amphetamine (3 mg/kg, ip) produced a taste aversion in rats and cats but not in ferrets which required a higher dose (> 5 mg/kg). The results of these experiments are interpreted as indicating that, at least for the ferret, there is no necessary relationship between toxin-induced illness and the acquisition of a CTA and that gastrointestinal distress is not a sufficient condition for CTA learning.

  20. 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...

  1. Hydrometer test for estimation of immunoglobulin concentration in bovine colostrum.

    Science.gov (United States)

    Fleenor, W A; Stott, G H

    1980-06-01

    A practical field method for measuring immunoglobulin concentration in bovine colostrum has been developed from the linear relationship between colostral specific gravity and immunoglobulin concentration. Fourteen colostrums were collected within 24 h postpartum from nursed and unnursed cows and were assayed for specific gravity and major colostral constituents. Additionally, 15 colostrums were collected immediately postpartum prior to suckling and assayed for specific gravity and immunoglobulin concentration. Regression analysis provided an equation to estimate colostral immunoglobulin concentration from the specific gravity of fresh whole colostrum. From this, a colostrometer was developed for practical field use.

  2. 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

  3. 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...

  4. 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...

  5. 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.

  6. 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.

  7. Serology and immunoglobulin profile in rheumatoid arthritis.

    Science.gov (United States)

    Adhya, S; Chakraborty, G; Hajra, B; Bhattacharya, S; Sikdar, P K; Sinha, S; Banerjee, P P; Ghosh, E; Chakraborty, P

    1998-01-01

    One hundred and twenty cases of clinically diagnosed rheumatoid arthritis, 80 non-rheumatoid cases suffering from various other diseases and 40 healthy individuals were investigated for the presence of rheumatoid factor, quantitation of serum immunoglobulin, demonstration of ANA and LE cell phenomenon. Microlatex agglutination test of serum for rheumatoid factor showed 56.6% positivity in rheumatoid group and 3.7% positivity in non-rheumatoid group. All three serum immunoglobulins (IgG, IgM, IgA) were raised in serum in significant titre in cases of rheumatoid arthritis, whereas only IgA lever was elevated in the group of non-rheumatoid diseases. ANA and LE cell phenomenon were observed in 11.7% and 4.4% cases of rheumatoid arthritis who had severe underlying disease. In non-rheumatoid group, only one of 6 cases of systemic lupus erythematosus showed rheumatoid factor and that too in an insignificant titre (less than 1:20). Synovium and synovial fluid contained plenty of plasma cells and lymphocytes. It has been observed that RF appears first in synovial fluid and it may take several months to a year to attain detectable level in serum.

  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. Levels of serum immunoglobulins in apparently healthy children and ...

    African Journals Online (AJOL)

    The results also confirm suggestions that levels of some immunoglobulin types seen amongst African adults may have possibly been attained during childhood. Our study could be of value since previous reports in this regard have been relatively scanty especially in this part of Nigeria. Keywords: Immunoglobulin, Immunity ...

  10. Levels of serum immunoglobulins in apparently healthy children and ...

    African Journals Online (AJOL)

    olayemitoyin

    suggestions that levels of some immunoglobulin types seen amongst African adults may have possibly been attained during childhood. Our study could be of value since previous reports in this regard have been relatively scanty especially in this part of Nigeria. Keywords: Immunoglobulin, Immunity, IgA, IgG, IgM.

  11. 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.

  12. INTERACTION OF ALBUMIN AND IMMUNOGLOBULIN G WITH SYNTHETIC HYDROXYAPATITE

    Directory of Open Access Journals (Sweden)

    E. Pylypchuk

    2012-12-01

    Full Text Available It was shown by X-ray phase analysis, IR spectra analysis and MALDI-ToF mass spectrometry methods that interaction of synthetic hydroxyapatite with a solution of immunoglobulin G leads to its partial dissolution due to leaching from the surface of calcium triphosphate which, in our opinion, forms complexes with immunoglobulin G.

  13. 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.

  14. Pathogenesis and transmission of avian influenza A (H7N9) virus in ferrets and mice.

    Science.gov (United States)

    Belser, Jessica A; Gustin, Kortney M; Pearce, Melissa B; Maines, Taronna R; Zeng, Hui; Pappas, Claudia; Sun, Xiangjie; Carney, Paul J; Villanueva, Julie M; Stevens, James; Katz, Jacqueline M; Tumpey, Terrence M

    2013-09-26

    On 29 March 2013, the Chinese Center for Disease Control and Prevention confirmed the first reported case of human infection with an avian influenza A(H7N9) virus. The recent human infections with H7N9 virus, totalling over 130 cases with 39 fatalities to date, have been characterized by severe pulmonary disease and acute respiratory distress syndrome (ARDS). This is concerning because H7 viruses have typically been associated with ocular disease in humans, rather than severe respiratory disease. This recent outbreak underscores the need to better understand the pathogenesis and transmission of these viruses in mammals. Here we assess the ability of A/Anhui/1/2013 and A/Shanghai/1/2013 (H7N9) viruses, isolated from fatal human cases, to cause disease in mice and ferrets and to transmit to naive animals. Both H7N9 viruses replicated to higher titre in human airway epithelial cells and in the respiratory tract of ferrets compared to a seasonal H3N2 virus. Moreover, the H7N9 viruses showed greater infectivity and lethality in mice compared to genetically related H7N9 and H9N2 viruses. The H7N9 viruses were readily transmitted to naive ferrets through direct contact but, unlike the seasonal H3N2 virus, did not transmit readily by respiratory droplets. The lack of efficient respiratory droplet transmission was corroborated by low receptor-binding specificity for human-like α2,6-linked sialosides. Our results indicate that H7N9 viruses have the capacity for efficient replication in mammals and human airway cells and highlight the need for continued public health surveillance of this emerging virus.

  15. The effect of cyclosporin-A on the oral microflora at gingival sulcus of the ferret.

    Science.gov (United States)

    Fischer, R G; Edwardsson, S; Klinge, B; Attström, R

    1996-09-01

    The effect of cyclosporin-A (CyA) on the dentogingival flora of ferrets with healthy and experimentally induced periodontal breakdown was studied. Five animals were given 10 mg/kg/d CyA. At the start of the experiments (day 0), ligatures were placed around 4 teeth in the right upper and lower jaws; corresponding contralateral teeth on the left side served as control. On days 0 and 28 (end of the experiment), microbiological samples were collected from the gingival sulcus of the experimental and the control teeth and from closely located gingival mucosa membrane. The samples were subjected to viable counts and to darkfield microscopic analyses. On day 0, facultative anaerobic rods, mainly Pasteurella spp, Alcaligenes spp, Corynebacterium spp. and Rothia spp dominated in the viable counts. No anaerobic bacteria were detected in the viable counts. On day 28 spirochetes increased in the experimental gingival sulcus samples and anaerobic bacteria appeared in most of the samples and constituted 40-60% of the total cultivable flora; Fusobacterium necrophorum and Eubacterium spp. predominated in the samples from the experimental sites. The results of the present study were compared with those of our previous investigation of ferrets not medicated with cyclosporin but also subject to experimental ligature periodontitis. Eubacterium spp. were absent in the animals not treated with cyclosporin, while this species was frequently present in the immunosuppressed ferrets. The results indicate that the presence of the large numbers of gram negative rods and of anaerobic bacteria may have enhanced the inflammatory process and further provoked the gingival overgrowth observed.

  16. A chimeric measles virus with canine distemper envelope protects ferrets from lethal distemper challenge.

    Science.gov (United States)

    Rouxel, Ronan Nicolas; Svitek, Nicholas; von Messling, Veronika

    2009-08-06

    CDV infects a broad range of carnivores, and over the past decades it has caused outbreaks in a variety of wild carnivore populations. Since the currently available live-attenuated vaccine is not sufficiently safe in these highly susceptible species, we produced a chimeric virus combining the replication complex of the measles Moraten vaccine strain with the envelope of a recent CDV wild type isolate. The resulting virus did not cause disease or immunosuppression in ferrets and conferred protection from challenge with a lethal wild type strain, demonstrating its potential value for wildlife conservation efforts.

  17. Mycobacterial lesions in fish, amphibians, reptiles, rodents, lagomorphs, and ferrets with reference to animal models.

    Science.gov (United States)

    Reavill, Drury R; Schmidt, Robert E

    2012-01-01

    Mycobacteriosis is a serious disease across many animal species. Approximately more than 120 species are currently recognized in the genus Mycobacterium. This article describes the zoonotic potential of mycobacteria and mycobacteriosis in fish, amphibians, rodents, rabbits, and ferrets. It considers clinical signs; histology; molecular methods of identification, such as polymerase chain reaction and DNA sequencing; routes of infection; and disease progression. Studying the disease in animals may aid in understanding the pathogenesis of mycobacterial infections in humans and identify better therapy and preventative options such as vaccines.

  18. Leucocytes, cytokines and satellite cells

    DEFF Research Database (Denmark)

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

    2012-01-01

    uncertain. The COX enzymes regulate satellite cell activity, as demonstrated in animal models; however the roles of the COX enzymes in human skeletal muscle need further investigation. We suggest using the term 'muscle damage' with care. Comparisons between studies and individuals must consider changes......-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...

  19. 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.

  20. Immunoglobulin G4-Related Disease: An Update

    Directory of Open Access Journals (Sweden)

    Abdullah Al-Mujaini

    2018-03-01

    Full Text Available Immunoglobulin G4-related disease (IgG4-RD is an increasingly recognized immune-mediated condition comprised of a collection of disorders that share specific pathological, serological, and clinical features. IgG4-RD is a fibroinflammatory condition with a tendency to form tumors with inflammatory infiltrate with IgG4 rich plasma cells and elevation of serum IgG4, which may affect virtually every organ and tissue. IgG4-related ophthalmic disease may present as dacryoadenitis, myositis, or involvement of other orbital tissue. Hypophysitis or pachymeningitis may manifest as cranial neuropathies. The diagnosis of IgG4-RD is based on a typical clinical scenario, supportive laboratory test, expected radiological characteristics, and distinct histopathological and immunohistochemical features. Corticosteroids and immunosuppressives form the mainline treatment.

  1. 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.

  2. Structural repertoire of immunoglobulin λ light chains

    KAUST Repository

    Chailyan, Anna; Marcatili, Paolo; Cirillo, Davide; Tramontano, Anna

    2011-01-01

    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.

  3. 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.

  4. 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.

  5. An outbreak of post-vaccinal suspected distemper-like encephalitis in farmed ferrets (Mustela putorius furo).

    Science.gov (United States)

    Gill, J M; Hartley, W J; Hodgkinson, N L

    1988-12-01

    Two outbreaks of an encephalitis apparently induced by an attenuated live distemper vaccine occurred in a large ferret breeding establishment in New Zealand. Approximately 350 of 6,000 young ferrets 16-22 weeks old died. Many were found dead with no premonitory signs, others showed severe neurological signs. Some with central nervous system (C.N.S.) signs recovered. Pathological examination showed no gross abnormalities except for a few with mild conjunctivitis, rhinitis and lung emphysema. Microscopically there was a moderate to massive non-inflammatory necrosis of hippocampal nerve cell bodies. In those animals which survived for several days with CNS signs there was also a mild to moderately severe non-supportive encephalitis, and in some of these distinct neuronal intranuclear and intracytoplasmic eosinophilic inclusion bodies were seen. Some ferrets also had a bronchiolitis with intracytoplasmic eosinophilic inclusion bodies in bronchiolar epithelium. All these lesions suggest that a distemper like condition was involved. About half of the ferrets also had a mild to severe inflammatory myocardial necrosis.

  6. 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...

  7. 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.

  8. 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.

  9. A proposal to conserve black-footed ferrets and the prairie dog ecosystem

    Science.gov (United States)

    Miller, Brian; Wemmer, Christen; Biggins, Dean; Reading, Richard

    1990-11-01

    Prairie dogs ( Cynomys spp.) have been poisoned throughout this century because of grazing competition with livestock. Recent evidence showed these early claims were exaggerated, but animal control was already entrenched in government policy. As a result, ongoing government subsidized poisoning has reduced prairie dogs to about 2% of their former distribution. The reduction of prairie dogs diminished species diversity in the arid grasslands of North America, including the potential extinction of the black-footed ferret ( Mustela nigripes). Cost-benefit analysis revealed that poisoning costs more than any grazing benefits accrued. This analysis did not consider the long-term costs of reversing ecosystem degradation, the intangible value of biological diversity as a public benefit, or the depletion of biotic resources as a loss of actual or potential wealth. The government presently finances the poisoning policy and the preservation of endangered species like the black-footed ferret, two apparently conflicting programs. We, therefore, propose an integrated management plan that considers both interests. We propose that federal monies allocated to the poisoning program be converted into a rebate for ranchers who manage livestock while preserving the prairie dog community. This would redirect funds and personnel already allocated to prairie dog eradication to an incentive for ranchers who manage for livestock and wildlife. Livestock interests and grassland biotic diversity would both benefit.

  10. Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines.

    Science.gov (United States)

    See, Raymond H; Petric, Martin; Lawrence, David J; Mok, Catherine P Y; Rowe, Thomas; Zitzow, Lois A; Karunakaran, Karuna P; Voss, Thomas G; Brunham, Robert C; Gauldie, Jack; Finlay, B Brett; Roper, Rachel L

    2008-09-01

    Although the 2003 severe acute respiratory syndrome (SARS) outbreak was controlled, repeated transmission of SARS coronavirus (CoV) over several years makes the development of a SARS vaccine desirable. We performed a comparative evaluation of two SARS vaccines for their ability to protect against live SARS-CoV intranasal challenge in ferrets. Both the whole killed SARS-CoV vaccine (with and without alum) and adenovirus-based vectors encoding the nucleocapsid (N) and spike (S) protein induced neutralizing antibody responses and reduced viral replication and shedding in the upper respiratory tract and progression of virus to the lower respiratory tract. The vaccines also diminished haemorrhage in the thymus and reduced the severity and extent of pneumonia and damage to lung epithelium. However, despite high neutralizing antibody titres, protection was incomplete for all vaccine preparations and administration routes. Our data suggest that a combination of vaccine strategies may be required for effective protection from this pathogen. The ferret may be a good model for SARS-CoV infection because it is the only model that replicates the fever seen in human patients, as well as replicating other SARS disease features including infection by the respiratory route, clinical signs, viral replication in upper and lower respiratory tract and lung damage.

  11. Acute and subchronic toxicity of naturally weathered Exxon Valdez crude oil in mallards and ferrets

    International Nuclear Information System (INIS)

    Stubblefield, W.A.; Hancock, G.A.; Ford, W.H.; Ringer, R.K.

    1995-01-01

    The toxic properties of naturally weathered Exxon Valdez crude oil (WEVC) were assessed in a battery of acute and subchronic toxicity tests using mallards, Anas platyrhynchos, and European ferrets, Mustela putorius. Adult mallard acute oral toxicity study results indicated no mortalities or signs o toxicity, i.e., no-observed-adverse-effect level (NOAEL) and median lethal dose (LD50) > 5,000 mg/kg. Acute oral feeding and food avoidance tests with ducklings also indicated no toxicity (NOAEL and LC50 > 50,000 mg/kg diet) with no evidence of food avoidance (FAC50 > 20,000 mg/kg diet). No mortalities or toxic signs were noted in a 14-d feeding study with adult birds at dietary concentrations up to 100,000 mg WEVC/kg diet. Among clinical and physiological end points evaluated, the only significant difference noted was an increase in liver: body weight ratios in the 100,000-mg WEVC/kg diet dose group. No differences in clinical chemistry or hematological parameters were noted, and there were no consistent differences in histological evaluations of organ tissues. Daily oral doses of up to 5,000 mg/kg of WEVC over 5 d resulted in minimal effects on ferrets. Increased serum albumin concentrations were observed in the 5,000-mg/kg dose group females and decreased spleen weights were noted in females of all WEVC treatment groups. No other significant observations were noted

  12. Oral Modeling of an Adenovirus-Based Quadrivalent Influenza Vaccine in Ferrets and Mice.

    Science.gov (United States)

    Scallan, Ciaran D; Lindbloom, Jonathan D; Tucker, Sean N

    2016-06-01

    Oral vaccines delivered as tablets offer a number of advantages over traditional parenteral-based vaccines including the ease of delivery, lack of needles, no need for trained medical personnel, and the ability to formulate into temperature-stable tablets. We have been evaluating an oral vaccine platform based on recombinant adenoviral vectors for the purpose of creating a prophylactic vaccine to prevent influenza, and have demonstrated vaccine efficacy in animal models and substantial immunogenicity in humans. These studies have evaluated monovalent vaccines to date. To protect against the major circulating A and B influenza strains, a multivalent influenza vaccine will be required. In this study, the immunogenicity of orally delivered monovalent, bivalent, trivalent, and quadrivalent vaccines was tested in ferrets and mice. The various vaccine combinations were tested by blending monovalent recombinant adenovirus vaccines, each expressing hemagglutinin from a single strain. Human tablet delivery was modeled in animals by oral gavage in mice and by endoscopic delivery in ferrets. We demonstrated minimal interference between the various vaccine vectors when used in combination and that the oral quadrivalent vaccine compared favorably to an approved trivalent inactivated vaccine. The quadrivalent vaccine presented here produced immune responses that we predict should be capable of providing protection against multiple influenza strains, and the platform should have applications to other multivalent vaccines. Vaxart, Inc.

  13. Dorso-Lateral Frontal Cortex of the Ferret Encodes Perceptual Difficulty during Visual Discrimination.

    Science.gov (United States)

    Zhou, Zhe Charles; Yu, Chunxiu; Sellers, Kristin K; Fröhlich, Flavio

    2016-03-30

    Visual discrimination requires sensory processing followed by a perceptual decision. Despite a growing understanding of visual areas in this behavior, it is unclear what role top-down signals from prefrontal cortex play, in particular as a function of perceptual difficulty. To address this gap, we investigated how neurons in dorso-lateral frontal cortex (dl-FC) of freely-moving ferrets encode task variables in a two-alternative forced choice visual discrimination task with high- and low-contrast visual input. About two-thirds of all recorded neurons in dl-FC were modulated by at least one of the two task variables, task difficulty and target location. More neurons in dl-FC preferred the hard trials; no such preference bias was found for target location. In individual neurons, this preference for specific task types was limited to brief epochs. Finally, optogenetic stimulation confirmed the functional role of the activity in dl-FC before target touch; suppression of activity in pyramidal neurons with the ArchT silencing opsin resulted in a decrease in reaction time to touch the target but not to retrieve reward. In conclusion, dl-FC activity is differentially recruited for high perceptual difficulty in the freely-moving ferret and the resulting signal may provide top-down behavioral inhibition.

  14. Vaccination against Canine Distemper Virus Infection in Infant Ferrets with and without Maternal Antibody Protection, Using Recombinant Attenuated Poxvirus Vaccines

    Science.gov (United States)

    Welter, Janet; Taylor, Jill; Tartaglia, James; Paoletti, Enzo; Stephensen, Charles B.

    2000-01-01

    Canine distemper virus (CDV) infection of ferrets is clinically and immunologically similar to measles, making this a useful model for the human disease. The model was used to determine if parenteral or mucosal immunization of infant ferrets at 3 and 6 weeks of age with attenuated vaccinia virus (NYVAC) or canarypox virus (ALVAC) vaccine strains expressing the CDV hemagglutinin (H) and fusion (F) protein genes (NYVAC-HF and ALVAC-HF) would induce serum neutralizing antibody and protect against challenge infection at 12 weeks of age. Ferrets without maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 5) or ALVAC-HF (n = 4) developed significant neutralizing titers (log10 inverse mean titer ± standard deviation of 2.30 ± 0.12 and 2.20 ± 0.34, respectively) by the day of challenge, and all survived with no clinical or virologic evidence of infection. Ferrets without maternal antibody that were vaccinated intranasally (i.n.) developed lower neutralizing titers, with NYVAC-HF producing higher titers at challenge (1.11 ± 0.57 versus 0.40 ± 0.37, P = 0.02) and a better survival rate (6/7 versus 0/5, P = 0.008) than ALVAC-HF. Ferrets with maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 7) and ALVAC-HF (n = 7) developed significantly higher antibody titers (1.64 ± 0.54 and 1.28 ± 0.40, respectively) than did ferrets immunized with an attenuated CDV vaccine (0.46 ± 0.59; n = 7) or the recombinant vectors expressing rabies glycoprotein (RG) (0.19 ± 0.32; n = 8, P = 7 × 10−6). The NYVAC vaccine also protected against weight loss, and both the NYVAC and attenuated CDV vaccines protected against the development of some clinical signs of infection, although survival in each of the three vaccine groups was low (one of seven) and not significantly different from the RG controls (none of eight). Combined i.n.-parenteral immunization of ferrets with maternal antibody using NYVAC-HF (n = 9) produced higher titers (1.63 ± 0

  15. 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

  16. Vaccination against canine distemper virus infection in infant ferrets with and without maternal antibody protection, using recombinant attenuated poxvirus vaccines.

    Science.gov (United States)

    Welter, J; Taylor, J; Tartaglia, J; Paoletti, E; Stephensen, C B

    2000-07-01

    Canine distemper virus (CDV) infection of ferrets is clinically and immunologically similar to measles, making this a useful model for the human disease. The model was used to determine if parenteral or mucosal immunization of infant ferrets at 3 and 6 weeks of age with attenuated vaccinia virus (NYVAC) or canarypox virus (ALVAC) vaccine strains expressing the CDV hemagglutinin (H) and fusion (F) protein genes (NYVAC-HF and ALVAC-HF) would induce serum neutralizing antibody and protect against challenge infection at 12 weeks of age. Ferrets without maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 5) or ALVAC-HF (n = 4) developed significant neutralizing titers (log(10) inverse mean titer +/- standard deviation of 2.30 +/- 0.12 and 2.20 +/- 0.34, respectively) by the day of challenge, and all survived with no clinical or virologic evidence of infection. Ferrets without maternal antibody that were vaccinated intranasally (i.n.) developed lower neutralizing titers, with NYVAC-HF producing higher titers at challenge (1.11 +/- 0.57 versus 0.40 +/- 0.37, P = 0.02) and a better survival rate (6/7 versus 0/5, P = 0.008) than ALVAC-HF. Ferrets with maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 7) and ALVAC-HF (n = 7) developed significantly higher antibody titers (1.64 +/- 0. 54 and 1.28 +/- 0.40, respectively) than did ferrets immunized with an attenuated CDV vaccine (0.46 +/- 0.59; n = 7) or the recombinant vectors expressing rabies glycoprotein (RG) (0.19 +/- 0.32; n = 8, P = 7 x 10(-6)). The NYVAC vaccine also protected against weight loss, and both the NYVAC and attenuated CDV vaccines protected against the development of some clinical signs of infection, although survival in each of the three vaccine groups was low (one of seven) and not significantly different from the RG controls (none of eight). Combined i.n.-parenteral immunization of ferrets with maternal antibody using NYVAC-HF (n = 9) produced higher titers (1

  17. 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.

  18. 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.

  19. 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.

  20. 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

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

    Directory of Open Access Journals (Sweden)

    Anthony C Marriott

    Full Text Available 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.

  2. 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

  3. 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.

  4. 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

  5. 7(th) International Immunoglobulin Conference: Poster presentations.

    Science.gov (United States)

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

    2014-12-01

    Immunoglobulin (Ig) therapy is the mainstay of treatment for primary antibody deficiency disorders and has proved to be efficacious in specific autoimmune and inflammatory diseases. Additionally, due to the role of Ig in complement activation, it is being used increasingly in solid organ transplantation. Furthermore, Ig is the primary or secondary treatment in some immune-mediated neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) or multifocal motor neuropathy (MMN). This session discusses trends of Ig use in Europe, proposed mechanisms of action, adverse effects and the potential role of Ig therapy in transplantation. Dr Šedivá reported that Ig therapy is available in all European countries, although dosing is not always optimal, due partly to reimbursement plans. Subcutaneous immunoglobulin (SCIg) has become increasingly accessible in recent years; however, the chosen route of administration still varies widely between countries. Dr Berger's presentation on optimization of Ig therapy in neuropathies, and Dr Rojavin's report on a pharmacometric model to determine the serum IgG levels achieved by different dosing regimens in primary antibody deficiency (PAD) patients, led to the challenging concept of using individualized dosing strategies. Dr Klehmet reported on the potential benefit of using antigen-specific T cell responses as a biomarker of IVIg responsiveness in CIDP patients, while Dr von Gunten provided an insight into the mechanisms of action of Ig preparations, suggesting that the immunoregulatory effects of IgG may be mediated by IgG antibodies against glycans. Dr Basta reported on the potential thrombogenic adverse effects associated with Ig therapy. Although these adverse events are rare, further studies are needed to clarify the relationship between Ig replacement and immunomodulatory therapy and these adverse reactions. In transplantation, Dr Carbone described that prophylactic IVIg treatment was found to decrease the

  6. Canine distemper virus (CDV) infection of ferrets as a model for testing Morbillivirus vaccine strategies: NYVAC- and ALVAC-based CDV recombinants protect against symptomatic infection.

    OpenAIRE

    Stephensen, C B; Welter, J; Thaker, S R; Taylor, J; Tartaglia, J; Paoletti, E

    1997-01-01

    Canine distemper virus (CDV) infection of ferrets causes an acute systemic disease involving multiple organ systems, including the respiratory tract, lymphoid system, and central nervous system (CNS). We have tested candidate CDV vaccines incorporating the fusion (F) and hemagglutinin (HA) proteins in the highly attenuated NYVAC strain of vaccinia virus and in the ALVAC strain of canarypox virus, which does not productively replicate in mammalian hosts. Juvenile ferrets were vaccinated twice ...

  7. 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.

  8. Pattern of intravenous immunoglobulins (IVIG) use in a pediatric ...

    African Journals Online (AJOL)

    Pattern of intravenous immunoglobulins (IVIG) use in a pediatric intensive care facility in a resource limited setting. ... Journal Home > Vol 13, No 2 (2013) > ... Results: The clinical diagnoses included neurology (35%), neonatology (16%), ...

  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. 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 ...

  11. Cytokine Response to Exercise and Its Modulation

    OpenAIRE

    Katsuhiko Suzuki

    2018-01-01

    Strenuous exercise induces such inflammatory responses as leukocytosis (neutrophilia) and symptoms as delayed-onset muscle soreness and swelling. However, the association between inflammatory mediator cytokines and oxidative stress is not fully delineated. Herein, in addition to basic background information on cytokines, research findings on exertional effects on cytokine release and the underlying mechanisms and triggers are introduced. Then, the associations among cytokine responses, oxidat...

  12. 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

    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....... 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...

  13. Purification, characterization and ELISA detection of mink immunoglobulins

    DEFF Research Database (Denmark)

    Martel, Cyril Jean-Marie; Aasted, Bent

    2008-01-01

    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. The purities of purified IgG, IgM and IgA were estimated by immunoglobulin class specific ELISAs to be more than 90% for IgG and IgM, and more than 80% for IgA....

  14. Degalactosylated/Desialylated Bovine Colostrum Induces Macrophage Phagocytic Activity Independently of Inflammatory Cytokine Production.

    Science.gov (United States)

    Uto, Yoshihiro; Kawai, Tomohito; Sasaki, Toshihide; Hamada, Ken; Yamada, Hisatsugu; Kuchiike, Daisuke; Kubo, Kentaro; Inui, Toshio; Mette, Martin; Tokunaga, Ken; Hayakawa, Akio; Go, Akiteru; Oosaki, Tomohiro

    2015-08-01

    Colostrum contains antibodies, such as immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM), and, therefore, has potent immunomodulating activity. In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). In the present study, we investigated the macrophage-activating effects of degalactosylated/desialylated bovine colostrum. We detected the positive band in degalactosylated/ desialylated bovine colostrum by western blotting using Helix pomatia agglutinin lectin. We also found that degalactosylated/ desialylated bovine colostrum could significantly enhance the phagocytic activity of mouse peritoneal macrophages in vitro and of intestinal macrophages in vivo. Besides, degalactosylated/desialylated bovine colostrum did not mediate the production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum can be used as a potential macrophage activator for various immunotherapies. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  15. Canine distemper virus (CDV) infection of ferrets as a model for testing Morbillivirus vaccine strategies: NYVAC- and ALVAC-based CDV recombinants protect against symptomatic infection.

    Science.gov (United States)

    Stephensen, C B; Welter, J; Thaker, S R; Taylor, J; Tartaglia, J; Paoletti, E

    1997-02-01

    Canine distemper virus (CDV) infection of ferrets causes an acute systemic disease involving multiple organ systems, including the respiratory tract, lymphoid system, and central nervous system (CNS). We have tested candidate CDV vaccines incorporating the fusion (F) and hemagglutinin (HA) proteins in the highly attenuated NYVAC strain of vaccinia virus and in the ALVAC strain of canarypox virus, which does not productively replicate in mammalian hosts. Juvenile ferrets were vaccinated twice with these constructs, or with an attenuated live-virus vaccine, while controls received saline or the NYVAC and ALVAC vectors expressing rabies virus glycoprotein. Control animals did not develop neutralizing antibody and succumbed to distemper after developing fever, weight loss, leukocytopenia, decreased activity, conjunctivitis, an erythematous rash typical of distemper, CNS signs, and viremia in peripheral blood mononuclear cells (as measured by reverse transcription-PCR). All three CDV vaccines elicited neutralizing titers of at least 1:96. All vaccinated ferrets survived, and none developed viremia. Both recombinant vaccines also protected against the development of symptomatic distemper. However, ferrets receiving the live-virus vaccine lost weight, became lymphocytopenic, and developed the erythematous rash typical of CDV. These data show that ferrets are an excellent model for evaluating the ability of CDV vaccines to protect against symptomatic infection. Because the pathogenesis and clinical course of CDV infection of ferrets is quite similar to that of other Morbillivirus infections, including measles, this model will be useful in testing new candidate Morbillivirus vaccines.

  16. Immunoglobulin class-switch recombination deficiencies.

    Science.gov (United States)

    Durandy, Anne; Kracker, Sven

    2012-07-30

    Immunoglobulin class-switch recombination deficiencies (Ig-CSR-Ds) are rare primary immunodeficiencies characterized by defective switched isotype (IgG/IgA/IgE) production. Depending on the molecular defect in question, the Ig-CSR-D may be combined with an impairment in somatic hypermutation (SHM). Some of the mechanisms underlying Ig-CSR and SHM have been described by studying natural mutants in humans. This approach has revealed that T cell-B cell interaction (resulting in CD40-mediated signaling), intrinsic B-cell mechanisms (activation-induced cytidine deaminase-induced DNA damage), and complex DNA repair machineries (including uracil-N-glycosylase and mismatch repair pathways) are all involved in class-switch recombination and SHM. However, several of the mechanisms required for full antibody maturation have yet to be defined. Elucidation of the molecular defects underlying the diverse set of Ig-CSR-Ds is essential for understanding Ig diversification and has prompted better definition of the clinical spectrum of diseases and the development of increasingly accurate diagnostic and therapeutic approaches.

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

    DEFF Research Database (Denmark)

    Liszewski, Walter; Gniadecki, Robert

    2016-01-01

    due to a downregulation or absence of cytokines. Here, we review the diagnosis and clinical management of cytokine deficiency syndromes in dermatology. We will review the biology of cytokines, and the current approved indications for recombinant cytokines and anticytokine antibodies. We will also...

  18. Ebola Virus Binding to Tim-1 on T Lymphocytes Induces a Cytokine Storm

    Directory of Open Access Journals (Sweden)

    Patrick Younan

    2017-09-01

    Full Text Available Ebola virus (EBOV disease (EVD results from an exacerbated immunological response that is highlighted by a burst in the production of inflammatory mediators known as a “cytokine storm.” Previous reports have suggested that nonspecific activation of T lymphocytes may play a central role in this phenomenon. T-cell immunoglobulin and mucin domain-containing protein 1 (Tim-1 has recently been shown to interact with virion-associated phosphatidylserine to promote infection. Here, we demonstrate the central role of Tim-1 in EBOV pathogenesis, as Tim-1−/− mice exhibited increased survival rates and reduced disease severity; surprisingly, only a limited decrease in viremia was detected. Tim-1−/− mice exhibited a modified inflammatory response as evidenced by changes in serum cytokines and activation of T helper subsets. A series of in vitro assays based on the Tim-1 expression profile on T cells demonstrated that despite the apparent absence of detectable viral replication in T lymphocytes, EBOV directly binds to isolated T lymphocytes in a phosphatidylserine–Tim-1-dependent manner. Exposure to EBOV resulted in the rapid development of a CD4Hi CD3Low population, non-antigen-specific activation, and cytokine production. Transcriptome and Western blot analysis of EBOV-stimulated CD4+ T cells confirmed the induction of the Tim-1 signaling pathway. Furthermore, comparative analysis of transcriptome data and cytokine/chemokine analysis of supernatants highlight the similarities associated with EBOV-stimulated T cells and the onset of a cytokine storm. Flow cytometry revealed virtually exclusive binding and activation of central memory CD4+ T cells. These findings provide evidence for the role of Tim-1 in the induction of a cytokine storm phenomenon and the pathogenesis of EVD.

  19. A new high molecular weight immunoglobulin class from the carcharhine shark: implications for the properties of the primordial immunoglobulin.

    Science.gov (United States)

    Berstein, R M; Schluter, S F; Shen, S; Marchalonis, J J

    1996-04-16

    All immunoglobulins and T-cell receptors throughout phylogeny share regions of highly conserved amino acid sequence. To identify possible primitive immunoglobulins and immunoglobulin-like molecules, we utilized 3' RACE (rapid amplification of cDNA ends) and a highly conserved constant region consensus amino acid sequence to isolate a new immunoglobulin class from the sandbar shark Carcharhinus plumbeus. The immunoglobulin, termed IgW, in its secreted form consists of 782 amino acids and is expressed in both the thymus and the spleen. The molecule overall most closely resembles mu chains of the skate and human and a new putative antigen binding molecule isolated from the nurse shark (NAR). The full-length IgW chain has a variable region resembling human and shark heavy-chain (VH) sequences and a novel joining segment containing the WGXGT motif characteristic of H chains. However, unlike any other H-chain-type molecule, it contains six constant (C) domains. The first C domain contains the cysteine residue characteristic of C mu1 that would allow dimerization with a light (L) chain. The fourth and sixth domains also contain comparable cysteines that would enable dimerization with other H chains or homodimerization. Comparison of the sequences of IgW V and C domains shows homology greater than that found in comparisons among VH and C mu or VL, or CL thereby suggesting that IgW may retain features of the primordial immunoglobulin in evolution.

  20. Neural changes in periapical lesions after systemic steroids in the ferret.

    Science.gov (United States)

    Holland, G R

    1993-06-01

    This study was intended to clarify the relationship between the neural changes which occur around the apex of the ferret canine after pulpectomy and the inflammatory process induced by the procedure. In 12 young adult ferrets, under general anesthesia, the pulps in the mandibular canine teeth were removed and replaced with gutta percha and Grossman's sealer. Six of the animals were treated with dexamethasone to reduce the inflammatory response. Three months later, the animals, again under general anesthesia, were perfused with a fixative mixture. Three unoperated animals that had not been treated with dexamethasone were also perfused. The mandibular canine teeth and their supporting tissues were removed, processed, and serially sectioned. Three-dimensional reconstructions of the periapical lesions in each animal were assembled and their volumes measured. The density of innervation in the periapical region was estimated. The mean lesion volume in the pulpectomized animals not treated with dexamethasone was 3.54 (+/- 2.27) mm3 and in the dexamethasone-treated animals 1.33 (+/- 1.31) mm3. The differences were statistically significant when tested by the Mann-Whitney U test (p lesions. The innervation density beneath the canines in the pulpectomized animals not treated with dexamethasone was 164 units per mm2 (+/- 80) and in the steroid-treated animals 151 +/- 68 units per mm2. In the control, untreated animals, the innervation density was 22 +/- 10 units per mm2. The difference between the steroid-treated pulpectomized animals and the untreated pulpectomized animals was not statistically significant (p > 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)

  1. 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.

  2. 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

  3. Immunoglobulin heavy chain exclusion in the shark.

    Directory of Open Access Journals (Sweden)

    Karolina Malecek

    2008-06-01

    Full Text Available The adaptive immune system depends on specific antigen receptors, immunoglobulins (Ig in B lymphocytes and T cell receptors (TCR in T lymphocytes. Adaptive responses to immune challenge are based on the expression of a single species of antigen receptor per cell; and in B cells, this is mediated in part by allelic exclusion at the Ig heavy (H chain locus. How allelic exclusion is regulated is unclear; we considered that sharks, the oldest vertebrates possessing the Ig/TCR-based immune system, would yield insights not previously approachable and reveal the primordial basis of the regulation of allelic exclusion. Sharks have an IgH locus organization consisting of 15-200 independently rearranging miniloci (VH-D1-D2-JH-Cmu, a gene organization that is considered ancestral to the tetrapod and bony fish IgH locus. We found that rearrangement takes place only within a minilocus, and the recombining gene segments are assembled simultaneously and randomly. Only one or few H chain genes were fully rearranged in each shark B cell, whereas the other loci retained their germline configuration. In contrast, most IgH were partially rearranged in every thymocyte (developing T cell examined, but no IgH transcripts were detected. The distinction between B and T cells in their IgH configurations and transcription reveals a heretofore unsuspected chromatin state permissive for rearrangement in precursor lymphocytes, and suggests that controlled limitation of B cell lineage-specific factors mediate regulated rearrangement and allelic exclusion. This regulation may be shared by higher vertebrates in which additional mechanistic and regulatory elements have evolved with their structurally complex IgH locus.

  4. Serum immunoglobulin G4 levels and Graves' disease phenotype.

    Science.gov (United States)

    Martin, Carmen Sorina; Sirbu, Anca Elena; Betivoiu, Minodora Andreea; Florea, Suzana; Barbu, Carmen Gabriela; Fica, Simona Vasilica

    2017-02-01

    We investigated, at diagnosis, the relationship between serum immunoglobulin G4 levels and the main characteristics of Graves' disease: hyperthyroidism severity, goiter size, presence of active Graves' ophthalmopathy, antithyroid antibodies status, and titer. This prospective study included 80 newly diagnosed Graves' disease patients. The main parameters measured at diagnosis: thyroid-stimulating hormone, free thyroxine, free triiodothyronine, total triiodothyronine, thyroglobulin, antithyroid peroxidase antibodies, anti-thyroglobulin antibodies, thyroid-stimulating hormone receptor antibodies, immunoglobulin G4. In Graves' disease patients, serum immunoglobulin G4 levels were higher than in general population (p = 0.028) and higher in men compared to women (p = 0.002). Only one female patient with intense hypoechoic goiter, high anti-thyroglobulin antibody, and antithyroid peroxidase antibody titers had an elevated serum immunoglobulin G4 level at diagnosis. Patients with immunoglobulin G4 levels above the 75th percentile (>237.52 mg/dl, N = 20) were younger at Graves' ophthalmopathy onset (p 286.28 mg/dl, N = 8) had lower total triiodothyronine values (p = 0.001) than patients with IgG below the 90th percentile. No significant correlations were found between smoking status (p = 0.58), goiter size (p = 0.50), the presence of ophthalmopathy (p = 0.42) or thyroid-stimulating hormone receptor antibody titers (p = 0.45) and the mean value of immunoglobulin G4 levels at diagnosis. Our data suggest that Graves' disease patients with elevated immunoglobulin G4 levels at diagnosis have a phenotype characterized by higher anti-thyroglobulin antibody and antithyroid peroxidase antibody titers, less severe T3 hyperthyroidism, younger age at ophthalmopathy onset and require a shorter duration of the first methimazole treatment cycle.

  5. 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...

  6. 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...... hypoglycaemia may be due to direct effects of similar molecules on glucose metabolism. These molecules appear to be phospholipids and we suggest that when fully characterized they might form the basis of antitoxic therapy for malaria....

  7. 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

    2018-06-01

    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 the 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. Preexisting 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

  8. 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...... with additional focus on risk assessment of these new viruses. In this study, four European swine influenza viruses were assessed for their zoonotic potential. Two of the four viruses were enzootic viruses of subtype H1N2 (with avian-like H1) and H3N2 and two were new reassortants, one with avian-like H1...... 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...

  9. 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.

  10. 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.

  11. 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...

  12. 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.

  13. Ferrets as a Novel Animal Model for Studying Human Respiratory Syncytial Virus Infections in Immunocompetent and Immunocompromised Hosts

    Science.gov (United States)

    Stittelaar, Koert J.; de Waal, Leon; van Amerongen, Geert; Veldhuis Kroeze, Edwin J.B.; Fraaij, Pieter L.A.; van Baalen, Carel A.; van Kampen, Jeroen J.A.; van der Vries, Erhard; Osterhaus, Albert D.M.E.; de Swart, Rik L.

    2016-01-01

    Human respiratory syncytial virus (HRSV) is an important cause of severe respiratory tract disease in immunocompromised patients. Animal models are indispensable for evaluating novel intervention strategies in this complex patient population. To complement existing models in rodents and non-human primates, we have evaluated the potential benefits of an HRSV infection model in ferrets (Mustela putorius furo). Nine- to 12-month-old HRSV-seronegative immunocompetent or immunocompromised ferrets were infected with a low-passage wild-type strain of HRSV subgroup A (105 TCID50) administered by intra-tracheal or intra-nasal inoculation. Immune suppression was achieved by bi-daily oral administration of tacrolimus, mycophenolate mofetil, and prednisolone. Throat and nose swabs were collected daily and animals were euthanized four, seven, or 21 days post-infection (DPI). Virus loads were determined by quantitative virus culture and qPCR. We observed efficient HRSV replication in both the upper and lower respiratory tract. In immunocompromised ferrets, virus loads reached higher levels and showed delayed clearance as compared to those in immunocompetent animals. Histopathological evaluation of animals euthanized 4 DPI demonstrated that the virus replicated in the respiratory epithelial cells of the trachea, bronchi, and bronchioles. These animal models can contribute to an assessment of the efficacy and safety of novel HRSV intervention strategies. PMID:27314379

  14. Ferrets as a Novel Animal Model for Studying Human Respiratory Syncytial Virus Infections in Immunocompetent and Immunocompromised Hosts

    Directory of Open Access Journals (Sweden)

    Koert J. Stittelaar

    2016-06-01

    Full Text Available Human respiratory syncytial virus (HRSV is an important cause of severe respiratory tract disease in immunocompromised patients. Animal models are indispensable for evaluating novel intervention strategies in this complex patient population. To complement existing models in rodents and non-human primates, we have evaluated the potential benefits of an HRSV infection model in ferrets (Mustela putorius furo. Nine- to 12-month-old HRSV-seronegative immunocompetent or immunocompromised ferrets were infected with a low-passage wild-type strain of HRSV subgroup A (105 TCID50 administered by intra-tracheal or intra-nasal inoculation. Immune suppression was achieved by bi-daily oral administration of tacrolimus, mycophenolate mofetil, and prednisolone. Throat and nose swabs were collected daily and animals were euthanized four, seven, or 21 days post-infection (DPI. Virus loads were determined by quantitative virus culture and qPCR. We observed efficient HRSV replication in both the upper and lower respiratory tract. In immunocompromised ferrets, virus loads reached higher levels and showed delayed clearance as compared to those in immunocompetent animals. Histopathological evaluation of animals euthanized 4 DPI demonstrated that the virus replicated in the respiratory epithelial cells of the trachea, bronchi, and bronchioles. These animal models can contribute to an assessment of the efficacy and safety of novel HRSV intervention strategies.

  15. 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.

  16. 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.

  17. 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

  18. Cytokine-Modulating Strategies and Newer Cytokine Targets for Arthritis Therapy

    Directory of Open Access Journals (Sweden)

    Shivaprasad H. Venkatesha

    2014-12-01

    Full Text Available Cytokines are the key mediators of inflammation in the course of autoimmune arthritis and other immune-mediated diseases. Uncontrolled production of the pro-inflammatory cytokines such as interferon-γ (IFN-γ, tumor necrosis factor α (TNFα, interleukin-6 (IL-6, and IL-17 can promote autoimmune pathology, whereas anti-inflammatory cytokines including IL-4, IL-10, and IL-27 can help control inflammation and tissue damage. The pro-inflammatory cytokines are the prime targets of the strategies to control rheumatoid arthritis (RA. For example, the neutralization of TNFα, either by engineered anti-cytokine antibodies or by soluble cytokine receptors as decoys, has proven successful in the treatment of RA. The activity of pro-inflammatory cytokines can also be downregulated either by using specific siRNA to inhibit the expression of a particular cytokine or by using small molecule inhibitors of cytokine signaling. Furthermore, the use of anti-inflammatory cytokines or cytokine antagonists delivered via gene therapy has proven to be an effective approach to regulate autoimmunity. Unexpectedly, under certain conditions, TNFα, IFN-γ, and few other cytokines can display anti-inflammatory activities. Increasing awareness of this phenomenon might help develop appropriate regimens to harness or avoid this effect. Furthermore, the relatively newer cytokines such as IL-32, IL-34 and IL-35 are being investigated for their potential role in the pathogenesis and treatment of arthritis.

  19. Cytokine Response to Exercise and Its Modulation

    Directory of Open Access Journals (Sweden)

    Katsuhiko Suzuki

    2018-01-01

    Full Text Available Strenuous exercise induces such inflammatory responses as leukocytosis (neutrophilia and symptoms as delayed-onset muscle soreness and swelling. However, the association between inflammatory mediator cytokines and oxidative stress is not fully delineated. Herein, in addition to basic background information on cytokines, research findings on exertional effects on cytokine release and the underlying mechanisms and triggers are introduced. Then, the associations among cytokine responses, oxidative stress, and tissue damage are described not only in overloaded skeletal muscle, but also in other internal organs. Furthermore, we introduce preventive countermeasures against the exhaustive exercise-induced pathogenesis together with the possibility of antioxidant interventions.

  20. CYTOKINE REGULATION OF ULCEROGENESIS IN GASTRODUODENAL MUCOSA

    Directory of Open Access Journals (Sweden)

    L. V. Matveeva

    2013-01-01

    Full Text Available Ulcerogenesis in gastroduodenal mucosa area is a complex multistep process. Its, phases arecontrolled by interaction and activation of pro­ and antiinflammatory cytokine cascade. Present review article summarizes scientific data on impact of cytokines upon ulcerative and reparatory processes, a variety of their diagnostic and therapeutic options is defined. Evaluation of cytokine status, or, in some cases, cytokine genotyping in patients with stomach and duodenal ulcers, may predict clinical course of the disease, as well as efficiency of basic and eradication therapy, correction of the treatment.

  1. Inhibitory effects of methamphetamine on mast cell activation and cytokine/chemokine production stimulated by lipopolysaccharide in C57BL/6J mice.

    Science.gov (United States)

    Xue, Li; Geng, Yan; Li, Ming; Jin, Yao-Feng; Ren, Hui-Xun; Li, Xia; Wu, Feng; Wang, Biao; Cheng, Wei-Ying; Chen, Teng; Chen, Yan-Jiong

    2018-04-01

    Previous studies have demonstrated that methamphetamine (MA) influences host immunity; however, the effect of MA on lipopolysaccharide (LPS)-induced immune responses remains unknown. Mast cells (MCs) are considered to serve an important role in the innate and acquired immune response, but it remains unknown whether MA modulates MC activation and LPS-stimulated cytokine production. The present study aimed to investigate the effect of MA on LPS-induced MC activation and the production of MC-derived cytokines in mice. Markers for MC activation, including cluster of differentiation 117 and the type I high affinity immunoglobulin E receptor, were assessed in mouse intestines. Levels of MC-derived cytokines in the lungs and thymus were also examined. The results demonstrated that cytokines were produced in the bone marrow-derived mast cells (BMMCs) of mice. The present study demonstrated that MA suppressed the LPS-mediated MC activation in mouse intestines. MA also altered the release of MC cytokines in the lung and thymus following LPS stimulation. In addition, LPS-stimulated cytokines were decreased in the BMMCs of mice following treatment with MA. The present study demonstrated that MA may regulate LPS-stimulated MC activation and cytokine production.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. The effects of retinoic acid on immunoglobulin synthesis: Role of interleukin 6

    Energy Technology Data Exchange (ETDEWEB)

    Ballow, M.; Xiang, Shunan; Wang, Weiping; Brodsky, L. [Children`s Hospital of Buffalo, NY (United States)]|[State Univ. of New York, Buffalo, NY (United States)

    1996-05-01

    Retinoic acid (RA) and its parent compound, retinol (ROH, vitamin A), have been recognized as important immunopotentiating agents. Previous studies from our laboratory have demonstrated that PA can augment formalin-treated Staphylococcus aureus (SAC) stimulated immunoglobulin (Ig) synthesis of cord blood mononuclear cells (CBMC). To determine the mechanism(s) by which RA modulates Ig synthesis, we studied the effects of RA on B cells and cytokine production. The addition of RA (10{sup -5} to 10{sup -10} M) to Epstein-Barr virus (EBV)-transformed B-cell clones derived from either adult or cord blood B cells augmented Ig secretion twofold. In contrast, cell proliferation was inhibited as measured by {sup 3}H-thymidine incorporation. We evaluated two cytokines known to be constitutively produced by EBV cell lines, IL-1 and IL-6. While RA had no effect on IL-1 production, IL-6 synthesis was greatly enhanced (20- to 45-fold), which was also reflected by an increase in steady-state mRNA levels for IL-6 but not TNF-{alpha} or TGF-{beta} on Northern blot analysis. Polyclonal rabbit anti-IL-6 antibodies were used to block the augmenting effects of RA on Ig synthesis of adenoidal B cells. RA-induced augmentation in IgG and IgA synthesis was blocked 58 and 29%, respectively, by anti-IL-6 antibodies. These studies suggest that the enhancing effects of RA on Ig synthesis are mediated, at least in part, by the autocrine or paracrine effects of IL-6 on B-cell differentiation. 37 refs., 5 figs.

  8. 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

  9. Cytokine profile of cervical cancer cells

    NARCIS (Netherlands)

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

    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

  10. Serum immunoglobulin E and immunoglobulin G reactivity to Agaricus bisporus proteins in mushroom cultivation workers.

    Science.gov (United States)

    Khakzad, Z; Hedayati, M T; Mahdian, S; Mayahi, S

    2015-06-01

    Although molds are regarded as the main fungal allergen sources, evidence indicates that spores of Basidiomycota including Agaricus bisporus ( A. bisporus ) can be also found at high concentrations in the environment and may cause as many respiratory allergies as molds. The aim of the present study was to evaluate specific immunoglobulin E (IgE) and immunoglobulin G (IgG) antibodies against A. bisporus via immunoblotting technique in individuals working at mushroom cultivation centers. In this study, 72 workers involved in the cultivation and harvest of button mushrooms were enrolled. For the analysis of serum IgE and IgG, A. bisporus grown in Sabouraud dextrose broth was harvested and ruptured by liquid nitrogen and glass beads. The obtained sample was centrifuged and the supernatant was collected as "crude extract" (CE). CE was separated via Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE). The separated proteins were transferred to a nitrocellulose filter and the bands responsive to IgE and IgG were identified by anti-human conjugated antibodies. All participants were screened in terms of total IgE level. Among 72 workers, 18 (25%) had a total IgE level higher than 188 IU/mL. In SDS-PAGE, the CE of A. bisporus showed 23 different protein bands with a molecular weight range of 13-80 kDa. The sera of 23.6% and 55.5% of participants showed positive response, with specific IgE and IgG antibodies against A. bisporus in the blot, respectively. The bands with molecular weights of 62 and 68 kDa were the most reactive protein components of A. bisporus to specific IgE antibodies. Moreover, bands with molecular weights of 57 and 62 kDa showed the highest reactivity to IgG, respectively. Also, 62 and 68 kDa components were the most reactive bands with both specific IgG and IgE antibodies. The obtained findings revealed that A. bisporus has different allergens and antigens, which contribute to its potential as an aeroallergen in hypersensitivity

  11. 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...

  12. 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...

  13. 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...

  14. 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

  15. 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 ...

  16. 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

  17. Sensitive chain specific radioimmunoassay for human immunoglobulins using monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Sikora, K; Alderson, T St.J.; Ellis, J [Ludwig Institute for Cancer Research, Cambridge (UK)

    1983-02-25

    A sensitive radioimmunoassay is described for human immunoglobulins. This solid-phase assay uses commercially available monoclonal antibodies and is specific for different Ig chain types. Levels of less than 20 ng/ml Ig are detectable. The assay is suitable for the analysis of human hybridoma supernatants.

  18. Immunoglobulin therapy in hematologic neoplasms and after hematopoietic cell transplantation.

    Science.gov (United States)

    Ueda, Masumi; Berger, Melvin; Gale, Robert Peter; Lazarus, Hillard M

    2018-03-01

    Immunoglobulins are used to prevent or reduce infection risk in primary immune deficiencies and in settings which exploit its anti-inflammatory and immune-modulatory effects. Rigorous proof of immunoglobulin efficacy in persons with lympho-proliferative neoplasms, plasma cell myeloma, and persons receiving hematopoietic cell transplants is lacking despite many clinical trials. Further, there are few consensus guidelines or algorithms for use in these conditions. Rapid development of new therapies targeting B-cell signaling and survival pathways and increased use of chimeric antigen receptor T-cell (CAR-T) therapy will likely result in more acquired deficiencies of humoral immunity and infections in persons with cancer. We review immunoglobulin formulations and discuss efficacy and potential adverse effects in the context of preventing infections and in graft-versus-host disease. We suggest an algorithm for evaluating acquired deficiencies of humoral immunity in persons with hematologic neoplasms and recommend appropriate use of immunoglobulin therapy. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Alpha chain determinants on the membrane of immunoglobulin synthesizing cells

    NARCIS (Netherlands)

    Hijmans, W.; Schuit, H.R.E.; Radl, J.; Vossen, J.M.J.J.

    1974-01-01

    In a study of surface immunoglobulins (Ig) on lymphocytes from patients with paraproteinemia (1), we observed that a variable number of plasma cells not only contained intracellular Ig, but also had Ig on their surface, as shown in the vital technique of immunofluorescence. Moreover, in the bone

  20. 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 ...

  1. 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.

  2. 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....

  3. Solvent-Detergent Treatment of IgM-Enriched Immunoglobulin

    Directory of Open Access Journals (Sweden)

    Mojgan Pourmokhtar

    2003-08-01

    Full Text Available Viral safety of human plasma products plays a key role in their safe uses. Solvent- detergent (SD virus-inactivation method has gained widespread popularity in the manufacture of biological products. This treatment which inactivates lipid-enveloped viruses effectively consists of incubation of a plasma protein solution in the presence of a non-volatile organic solvent and a detergent. In this study, IgM-enriched immunoglobulin was incubated at 24 °C for 6 h under slow stirring in the presence of tri(n-butyl phosphate (0.3% w/w as solvent and tween 80 (1% w/w as detergent. After completion of the inactivation process and removal of the solvent-detergent, the ability of SD-treatment to remove Infectious Bovine Rhinotracheitis (IBR virus (a lipid-enveloped virus and Foot-and-Mouth Disease virus (a non-enveloped virus were evaluated by "virus spiking studies" using a scaled down process. Reduction factor of 4 log was obtained for the SD-treatment of IgM-enriched immunoglobulin spiked with IBR virus. No virus inactivation was observed in the SD-treated IgM-enriched immunoglobulin, spiked with Foot-and-Mouth Disease virus. It was concluded that treatment of IgM-enriched immunoglobulin with TNBP-TWEEN 80 may be considered as an efficient lipid-enveloped virus inactivation step in the manufacture of this product.

  4. 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,

  5. Effect of continuous milking on immunoglobulin concentrations in bovine colostrum

    NARCIS (Netherlands)

    Verweij, J.J.; Koets, A.P.; Eisenberg, S.W.F.

    2014-01-01

    Continuous milking is defined as a dairy cattle management system without a planned dry period for cows in late gestation. Continuous milking has been described to reduce health problems common in periparturient cattle, but may affect colostrum immunoglobulin (Ig) concentration and subsequently calf

  6. Cytokine signalling in embryonic stem cells

    DEFF Research Database (Denmark)

    Kristensen, David Møbjerg; Kalisz, Mark; Nielsen, Jens Høiriis

    2006-01-01

    Cytokines play a central role in maintaining self-renewal in mouse embryonic stem (ES) cells through a member of the interleukin-6 type cytokine family termed leukemia inhibitory factor (LIF). LIF activates the JAK-STAT3 pathway through the class I cytokine receptor gp130, which forms a trimeric...... pathways seem to converge on c-myc as a common target to promote self-renewal. Whereas LIF does not seem to stimulate self-renewal in human embryonic stem cells it cannot be excluded that other cytokines are involved. The pleiotropic actions of the increasing number of cytokines and receptors signalling...... via JAKs, STATs and SOCS exhibit considerable redundancy, compensation and plasticity in stem cells in accordance with the view that stem cells are governed by quantitative variations in strength and duration of signalling events known from other cell types rather than qualitatively different stem...

  7. 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.

  8. 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.

  9. Host gene expression profiles in ferrets infected with genetically distinct henipavirus strains.

    Directory of Open Access Journals (Sweden)

    Alberto J Leon

    2018-03-01

    Full Text Available Henipavirus infection causes severe respiratory and neurological disease in humans that can be fatal. To characterize the pathogenic mechanisms of henipavirus infection in vivo, we performed experimental infections in ferrets followed by genome-wide gene expression analysis of lung and brain tissues. The Hendra, Nipah-Bangladesh, and Nipah-Malaysia strains caused severe respiratory and neurological disease with animals succumbing around 7 days post infection. Despite the presence of abundant viral shedding, animal-to-animal transmission did not occur. The host gene expression profiles of the lung tissue showed early activation of interferon responses and subsequent expression of inflammation-related genes that coincided with the clinical deterioration. Additionally, the lung tissue showed unchanged levels of lymphocyte markers and progressive downregulation of cell cycle genes and extracellular matrix components. Infection in the brain resulted in a limited breadth of the host responses, which is in accordance with the immunoprivileged status of this organ. Finally, we propose a model of the pathogenic mechanisms of henipavirus infection that integrates multiple components of the host responses.

  10. 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.

  11. 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.

  12. 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.

  13. Swine Influenza Virus (H1N2) Characterization and Transmission in Ferrets, Chile.

    Science.gov (United States)

    Bravo-Vasquez, Nicolás; Karlsson, Erik A; Jimenez-Bluhm, Pedro; Meliopoulos, Victoria; Kaplan, Bryan; Marvin, Shauna; Cortez, Valerie; Freiden, Pamela; Beck, Melinda A; Hamilton-West, Christopher; Schultz-Cherry, Stacey

    2017-02-01

    Phylogenetic analysis of the influenza hemagglutinin gene (HA) has suggested that commercial pigs in Chile harbor unique human seasonal H1-like influenza viruses, but further information, including characterization of these viruses, was unavailable. We isolated influenza virus (H1N2) from a swine in a backyard production farm in Central Chile and demonstrated that the HA gene was identical to that in a previous report. Its HA and neuraminidase genes were most similar to human H1 and N2 viruses from the early 1990s and internal segments were similar to influenza A(H1N1)pdm09 virus. The virus replicated efficiently in vitro and in vivo and transmitted in ferrets by respiratory droplet. Antigenically, it was distinct from other swine viruses. Hemagglutination inhibition analysis suggested that antibody titers to the swine Chilean H1N2 virus were decreased in persons born after 1990. Further studies are needed to characterize the potential risk to humans, as well as the ecology of influenza in swine in South America.

  14. 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.

  15. The non-lemniscal auditory cortex in ferrets: convergence of corticotectal inputs in the superior colliculus

    Directory of Open Access Journals (Sweden)

    Victoria M Bajo

    2010-05-01

    Full Text Available Descending cortical inputs to the superior colliculus (SC contribute to the unisensory response properties of the neurons found there and are critical for multisensory integration. However, little is known about the relative contribution of different auditory cortical areas to this projection or the distribution of their terminals in the SC. We characterized this projection in the ferret by injecting tracers in the SC and auditory cortex. Large pyramidal neurons were labeled in layer V of different parts of the ectosylvian gyrus after tracer injections in the SC. Those cells were most numerous in the anterior ectosylvian gyrus (AEG, and particularly in the anterior ventral field, which receives both auditory and visual inputs. Labeling was also found in the posterior ectosylvian gyrus (PEG, predominantly in the tonotopically-organized posterior suprasylvian field. Profuse anterograde labeling was present in the SC following tracer injections at the site of acoustically-responsive neurons in the AEG or PEG, with terminal fields being both more prominent and clustered for inputs originating from the AEG. Terminals from both cortical areas were located throughout the intermediate and deep layers, but were most concentrated in the posterior half of the SC, where peripheral stimulus locations are represented. No inputs were identified from primary auditory cortical areas, although some labeling was found in the surrounding sulci. Our findings suggest that higher level auditory cortical areas, including those involved in multisensory processing, may modulate SC function via their projections into its deeper layers.

  16. 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.

  17. 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.

  18. Ebola Virus Binding to Tim-1 on T Lymphocytes Induces a Cytokine Storm.

    Science.gov (United States)

    Younan, Patrick; Iampietro, Mathieu; Nishida, Andrew; Ramanathan, Palaniappan; Santos, Rodrigo I; Dutta, Mukta; Lubaki, Ndongala Michel; Koup, Richard A; Katze, Michael G; Bukreyev, Alexander

    2017-09-26

    Ebola virus (EBOV) disease (EVD) results from an exacerbated immunological response that is highlighted by a burst in the production of inflammatory mediators known as a "cytokine storm." Previous reports have suggested that nonspecific activation of T lymphocytes may play a central role in this phenomenon. T-cell immunoglobulin and mucin domain-containing protein 1 (Tim-1) has recently been shown to interact with virion-associated phosphatidylserine to promote infection. Here, we demonstrate the central role of Tim-1 in EBOV pathogenesis, as Tim-1 -/- mice exhibited increased survival rates and reduced disease severity; surprisingly, only a limited decrease in viremia was detected. Tim-1 -/- mice exhibited a modified inflammatory response as evidenced by changes in serum cytokines and activation of T helper subsets. A series of in vitro assays based on the Tim-1 expression profile on T cells demonstrated that despite the apparent absence of detectable viral replication in T lymphocytes, EBOV directly binds to isolated T lymphocytes in a phosphatidylserine-Tim-1-dependent manner. Exposure to EBOV resulted in the rapid development of a CD4 Hi CD3 Low population, non-antigen-specific activation, and cytokine production. Transcriptome and Western blot analysis of EBOV-stimulated CD4 + T cells confirmed the induction of the Tim-1 signaling pathway. Furthermore, comparative analysis of transcriptome data and cytokine/chemokine analysis of supernatants highlight the similarities associated with EBOV-stimulated T cells and the onset of a cytokine storm. Flow cytometry revealed virtually exclusive binding and activation of central memory CD4 + T cells. These findings provide evidence for the role of Tim-1 in the induction of a cytokine storm phenomenon and the pathogenesis of EVD. IMPORTANCE Ebola virus infection is characterized by a massive release of inflammatory mediators, which has come to be known as a cytokine storm. The severity of the cytokine storm is

  19. Comparison of techniques of detecting immunoglobulin-binding protein reactivity to immunoglobulin produced by different avian and mammalian species.

    Science.gov (United States)

    Justiz-Vaillant, A A; Akpaka, P E; McFarlane-Anderson, N; Smikle, M F

    2013-01-01

    The rationale of this study was to use several immunological assays to investigate the reactivity of immunoglobulin binding protein (IBP) to immunoglobulins from various avian and mammalian species. The IBP studied were Staphylococcal protein A (SpA), Streptococcal protein G (SpG), Peptostreptococcal protein L (SpL) and recombinant protein LA (SpLA). The various immunological techniques used were double immunodiffusion (Ouchterlony technique) that tested positive high protein reactivities, direct and competitive enzyme-linked immunosorbent assays (ELISAs) that tested moderate and low positive protein binding capacities, respectively. In addition to sandwich ELISAs, immunoblot analyses and Ig-purification by SpA-affinity chromatography, which were sensitive tests and helpful in the screening and confirmatory tests were also used. The Ouchterlony technique showed that compared to the other proteins, SpLA had the highest range of reactivity with animal sera and purified immunoglobulins while SpL was least reactive. With the direct ELISA, SpL reacted with the raccoon sera, rabbit IgG and with IgY from bantam hens and pigeons. While with the direct ELISA, SpA reacted with sera from skunk, coyote, raccoon, mule, donkey and human. The sandwich ELISA revealed high reactivity of both SpG and SpLA with mammalian sera titres ranging from 1:32 (raccoon serum) to 1:1024 (mule and donkey sera). These results suggest that IBP can be used for the detection of immunoglobulin using various immunological assays and this is important for the diagnosis of infectious diseases in animal and bird populations studied and in the purification of immunoglobulins.

  20. 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.

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

    Science.gov (United States)

    Driskell, Elizabeth A; Pickens, Jennifer A; Humberd-Smith, Jennifer; Gordy, James T; Bradley, Konrad C; Steinhauer, David A; Berghaus, Roy D; Stallknecht, David E; Howerth, Elizabeth W; Tompkins, Stephen Mark

    2012-01-01

    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(α2,3)Gal]. 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.

  2. 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.

  3. [Complete genome sequencing and analyses of rabies viruses isolated from wild animals (Chinese Ferret-Badger) in Zhejiang province].

    Science.gov (United States)

    Lei, Yong-Liang; Wang, Xiao-Guang; Liu, Fu-Ming; Chen, Xiu-Ying; Ye, Bi-Feng; Mei, Jian-Hua; Lan, Jin-Quan; Tang, Qing

    2009-08-01

    Based on sequencing the full-length genomes of two Chinese Ferret-Badger, we analyzed the properties of rabies viruses genetic variation in molecular level to get information on prevalence and variation of rabies viruses in Zhejiang, and to enrich the genome database of rabies viruses street strains isolated from Chinese wildlife. Overlapped fragments were amplified by RT-PCR and full-length genomes were assembled to analyze the nucleotide and deduced protein similarities and phylogenetic analyses of the N genes from Chinese Ferret-Badger, sika deer, vole, dog. Vaccine strains were then determined. The two full-length genomes were completely sequenced to find out that they had the same genetic structure with 11 923 nts including 58 nts-Leader, 1353 nts-NP, 894 nts-PP, 609 nts-MP, 1575 nts-GP, 6386 nts-LP, and 2, 5, 5 nts- intergenic regions (IGRs), 423 nts-Pseudogene-like sequence (Psi), 70 nts-Trailer. The two full-length genomes were in accordance with the properties of Rhabdoviridae Lyssa virus by blast and multi-sequence alignment. The nucleotide and amino acid sequences among Chinese strains had the highest similarity, especially among animals of the same species. Of the two full-length genomes, the similarity in amino acid level was dramatically higher than that in nucleotide level, so that the nucleotide mutations happened in these two genomes were most probably as synonymous mutations. Compared to the referenced rabies viruses, the lengths of the five protein coding regions did not show any changes or recombination, but only with a few-point mutations. It was evident that the five proteins appeared to be stable. The variation sites and types of the two ferret badgers genomes were similar to the referenced vaccine or street strains. The two strains were genotype 1 according to the multi-sequence and phylogenetic analyses, which possessing the distinct geographyphic characteristics of China. All the evidence suggested a cue that these two ferret badgers

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.).

  9. Interactions between cytokines and nitric oxide.

    Science.gov (United States)

    Liew, F Y

    1995-01-01

    There is now an impressive range of evidence supporting the important role of cytokines in sleep regulation (see Krueger et al., 1995; De Simoni et al., 1995). It has also been reported that inhibition of nitric oxide (NO) synthesis suppresses sleep in rabbits (Kapás et al., 1994). This is not surprising, since NO is closely involved in neurotransmission (Garthwaite, 1991; Schuman and Madison, 1994) and cytokines are the major inducers of NO synthesis (Hibbs et al., 1990). Further, it is now clear that NO plays an important role in modulating immune responses, possibly through the differential regulation of cytokine synthesis (Taylor-Robinson et al., 1994). In this article, I will provide evidence for the interactions between cytokines and nitric oxide, and discuss their implications in the regulation of immune responses. I shall illustrate these mainly with results from my coworkers and I, from our laboratory rather than attempting an exhaustive review of the subject.

  10. 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...... level of IgG were reported in adult patients; however no studies have analyzed the increasing incidence in relation to Ig levels. Our aim was to describe Ig in children newly diagnosed with diabetes and in their healthy siblings. Children with T1D expressed significantly lower IgG (p

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

    African Journals Online (AJOL)

    SAM

    2014-05-28

    May 28, 2014 ... non-collagenous proteins (NCP) and signaling molecules ... periodontal tissues and by signals and cytokines production ... Dentin extract was stored at -80°C until use. .... An effective mechanism to prevent self-reactivity is the.

  12. Autoantibodies and immunoglobulins in alcoholic steatosis and cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Tage-Jensen, Ulrik Viggo

    1983-01-01

    increased (p less than 0.005) concentrations of immunoglobulins G, A, and M when compared to patients with steatosis. These results indicate that the degree of liver damage has more effect than chronic alcoholism on the humoral immune system. Whether this influence is direct or indirect remains......Antinuclear antibodies were significantly more prevalent (p less than 0.01) in 143 patients with alcoholic cirrhosis than in 64 patients with alcoholic steatosis and in 94 controls. Smooth muscle antibodies were significantly more prevalent (p less than 0.05) in patients with alcoholic steatosis...... and cirrhosis than in controls. The prevalence of antimitochondrial antibodies and IgG liver membrane antibodies did not differ significantly between the three groups. Immunoglobulin G, A, and M concentrations were only occasionally increased in patients with steatosis. Patients with cirrhosis had significantly...

  13. 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.

  14. A database of immunoglobulins with integrated tools: DIGIT.

    KAUST Repository

    Chailyan, Anna; Tramontano, Anna; Marcatili, Paolo

    2011-01-01

    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.

  15. 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.

  16. Beneficial effects of cytokine induced hyperlipidemia.

    Science.gov (United States)

    Feingold, K R; Hardardóttir, I; Grunfeld, C

    1998-01-01

    Infection, inflammation and trauma induce marked changes in the plasma levels of a wide variety of proteins (acute phase response), and these changes are mediated by cytokines. The acute phase response is thought to be beneficial to the host. The host's response to injury also results in dramatic alterations in lipid metabolism and circulating lipoprotein levels which are mediated by cytokines. A large number of cytokines including TNF, the interleukins, and the interferons increase serum triglyceride levels. This rapid increase (1-2 h) is predominantly due to an increase in hepatic VLDL secretion while the late increase may be due to a variety of factors including increased hepatic production of VLDL or delayed clearance secondary to a decrease in lipoprotein lipase activity and/or apolipoprotein E levels on VLDL. In animals other than primates, cytokines also increase serum cholesterol levels, most likely by increasing hepatic cholesterol. Cytokines increase hepatic cholesterol synthesis by stimulating HMG CoA reductase gene expression and decrease hepatic cholesterol catabolism by inhibiting cholesterol 7 alpha-hydroxylase, the key enzyme in bile acid synthesis. Injury and/or cytokines also decrease HDL cholesterol levels and induce alterations in the composition of HDL. The content of SAA and apolipoprotein J increase, apolipoprotein A1 may decrease, and the cholesterol ester content decreases while free cholesterol increases. Additionally, key proteins involved in HDL metabolism are altered by cytokines; LCAT activity, hepatic lipase activity, and CETP levels decrease. These changes in lipid and lipoprotein metabolism may be beneficial in a number of ways including: lipoproteins competing with viruses for cellular receptors, apolipoproteins neutralizing viruses, lipoproteins binding and targeting parasites for destruction, apolipoproteins lysing parasites, redistribution of nutrients to cells involved in the immune response and/or tissue repair, and

  17. Fungicidal activity of peptides encoded by immunoglobulin genes

    OpenAIRE

    Polonelli, Luciano; Ciociola, Tecla; Sperind?, Martina; Giovati, Laura; D?Adda, Tiziana; Galati, Serena; Travassos, Luiz R.; Magliani, Walter; Conti, Stefania

    2017-01-01

    Evidence from previous works disclosed the antimicrobial, antiviral, anti-tumour and/or immunomodulatory activity exerted, through different mechanisms of action, by peptides expressed in the complementarity-determining regions or even in the constant region of antibodies, independently from their specificity and isotype. Presently, we report the selection, from available databases, of peptide sequences encoded by immunoglobulin genes for the evaluation of their potential biological activitie...

  18. CD147 Immunoglobulin Superfamily Receptor Function and Role in Pathology

    OpenAIRE

    Iacono, Kathryn T.; Brown, Amy L.; Greene, Mark I.; Saouaf, Sandra J.

    2007-01-01

    The immunoglobulin superfamily member CD147 plays an important role in fetal, neuronal, lymphocyte and extracellular matrix development. Here we review the current understanding of CD147 expression and protein interactions with regard to CD147 function and its role in pathologic conditions including heart disease, Alzheimer’s disease, stroke and cancer. A model linking hypoxic conditions found within the tumor microenvironment to up-regulation of CD147 expression and tumor progression is intr...

  19. 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

  20. 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 ...

  1. 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.

  2. 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.

  3. 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.

  4. Experimental oral immunization of ferret badgers (Melogale moschata) with a recombinant canine adenovirus vaccine CAV-2-E3Δ-RGP and an attenuated rabies virus SRV9.

    Science.gov (United States)

    Zhao, Jinghui; Liu, Ye; Zhang, Shoufeng; Fang, Lijun; Zhang, Fei; Hu, Rongliang

    2014-04-01

    Ferret badgers (Melogale moschata) are a major reservoir of rabies virus in southeastern China. Oral immunization has been shown to be a practical method for wildlife rabies management in Europe and North America. Two groups of 20 ferret badgers were given a single oral dose of a recombinant canine adenovirus-rabies vaccine, CAV-2-E3Δ-RGP, or an experimental attenuated rabies virus vaccine, SRV9. At 21 days, all ferret badgers had seroconverted, with serum virus-neutralizing antibodies ranging from 0.1 to 4.5 IU/mL. Titers were >0.50 IU/mL (an acceptable level) in 17/20 and 16/20 animals receiving CAV-2-E3Δ-RGP or SRV9, respectively. The serologic results indicate that the recombinant CAV-2-E3Δ-RGP is at least as effective as the attenuated rabies virus vaccine. Both may be considered for additional research as oral rabies vaccine candidates for ferret badgers.

  5. 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

  6. 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 use...

  7. New reassortant and enzootic European swine influenza viruses transmit efficiently through direct contact in the ferret model.

    Science.gov (United States)

    Fobian, Kristina; Fabrizio, Thomas P; Yoon, Sun-Woo; Hansen, Mette Sif; Webby, Richard J; Larsen, Lars E

    2015-07-01

    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 with additional focus on risk assessment of these new viruses. In this study, four European swine influenza viruses were assessed for their zoonotic potential. Two of the four viruses were enzootic viruses of subtype H1N2 (with avian-like H1) and H3N2, and two were new reassortants, one with avian-like H1 and human-like N2 and one with 2009 pandemic H1 and swine-like N2. All viruses replicated to high titres 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 titres. Further, the viruses revealed preferential binding to the 2,6-α-silalylated glycans and investigation of the antiviral susceptibility of the viruses revealed that all were sensitive to neuraminidase inhibitors. These findings suggested that these viruses have the potential to infect humans and further underline the need for continued surveillance as well as biological characterization of new influenza A viruses.

  8. Effect of fenspiride, a non-steroidal antiinflammatory agent, on neurogenic mucus secretion in ferret trachea in vitro.

    Science.gov (United States)

    Khawaja, A M; Liu, Y C; Rogers, D F

    1999-01-01

    Neural mechanisms contribute to control of mucus secretion in the airways. Fenspiride is a non-steroidal antiinflammatory agent which has a variety of actions, including inhibition of neurogenic bronchoconstriction. The effect of fenspiride on neurally-mediated mucus secretion was investigated in vitro in electrically-stimulated ferret trachea, using(35)SO(4)as a mucus marker. Cholinergic secretory responses were isolated using adrenoceptor and tachykinin receptor antagonists. Tachykinin responses were isolated using cholinoceptor and adrenoceptor antagonists. Electrical stimulation increased cholinergic secretion by;90% and tachykininergic secretion by;40%. Fenspiride (1 microM-1 mM) tended to inhibit cholinergic secretion in a concentration-dependent manner, although only at 1 mM was inhibition (by 87%) significant. Inhibition by fenspiride of tachykininergic secretion was not concentration-dependent, and again significant inhibition (by 85%) was only at 1 mM. Inhibition was not due to loss of tissue viability, as assessed by restitution of secretory response after washout. Fenspiride also inhibited secretion induced by acetylcholine, but did not inhibit substance P-induced secretion. Histamine receptor antagonists increased basal secretion by 164%, whereas fenspiride did not affect basal secretion. We conclude that, in ferret trachea in vitro, fenspiride inhibits neurally-mediated mucus secretion, with antimuscarinic action the most plausible mechanism of action, but not necessarily the only mechanism. Copyright 1999 Academic Press.

  9. 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...

  10. Antibody-cytokine fusion proteins for treatment of cancer: engineering cytokines for improved efficacy and safety.

    Science.gov (United States)

    Young, Patricia A; Morrison, Sherie L; Timmerman, John M

    2014-10-01

    The true potential of cytokine therapies in cancer treatment is limited by the inability to deliver optimal concentrations into tumor sites due to dose-limiting systemic toxicities. To maximize the efficacy of cytokine therapy, recombinant antibody-cytokine fusion proteins have been constructed by a number of groups to harness the tumor-targeting ability of monoclonal antibodies. The aim is to guide cytokines specifically to tumor sites where they might stimulate more optimal anti-tumor immune responses while avoiding the systemic toxicities of free cytokine therapy. Antibody-cytokine fusion proteins containing interleukin (IL)-2, IL-12, IL-21, tumor necrosis factor (TNF)α, and interferons (IFNs) α, β, and γ have been constructed and have shown anti-tumor activity in preclinical and early-phase clinical studies. Future priorities for development of this technology include optimization of tumor targeting, bioactivity of the fused cytokine, and choice of appropriate agents for combination therapies. This review is intended to serve as a framework for engineering an ideal antibody-cytokine fusion protein, focusing on previously developed constructs and their clinical trial results. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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.; Pei, Kurtis J. C.

    2018-01-01

    Background 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. Methodology/Principle findings 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. Conclusions/Significance 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

  18. 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, 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.

  19. Picroside II Attenuates Airway Inflammation by Downregulating the Transcription Factor GATA3 and Th2-Related Cytokines in a Mouse Model of HDM-Induced Allergic Asthma.

    Directory of Open Access Journals (Sweden)

    Jin Choi

    Full Text Available Picroside II isolated from Pseudolysimachion rotundum var. subintegrum has been used as traditional medicine to treat inflammatory diseases. In this study, we assessed whether picroside II has inhibitory effects on airway inflammation in a mouse model of house dust mite (HDM-induced asthma. In the HDM-induced asthmatic model, picroside II significantly reduced inflammatory cell counts in the bronchoalveolar lavage fluid (BALF, the levels of total immunoglobulin (Ig E and HDM-specific IgE and IgG1 in serum, airway inflammation, and mucus hypersecretion in the lung tissues. ELISA analysis showed that picroside II down-regulated the levels of Th2-related cytokines (including IL-4, IL-5, and IL-13 and asthma-related mediators, but it up-regulated Th1-related cytokine, IFNγ in BALF. Picroside II also inhibited the expression of Th2 type cytokine genes and the transcription factor GATA3 in the lung tissues of HDM-induced mice. Finally, we demonstrated that picroside II significantly decreased the expression of GATA3 and Th2 cytokines in developing Th2 cells, consistent with in vivo results. Taken together, these results indicate that picroside II has protective effects on allergic asthma by reducing GATA3 expression and Th2 cytokine bias.

  20. 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.

  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. 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)

  3. 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.

  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. Salivary cytokine levels in early gingival inflammation

    DEFF Research Database (Denmark)

    Belstrøm, Daniel; Damgaard, Christian; Könönen, Eija

    2017-01-01

    Salivary protein levels have been studied in periodontitis. However, there is lack of information on salivary cytokine levels in early gingival inflammation. The aim of this study was to determine salivary levels of vascular endothelial growth factor (VEGF), interleukin (IL)-8, monocyte chemoattr......Salivary protein levels have been studied in periodontitis. However, there is lack of information on salivary cytokine levels in early gingival inflammation. The aim of this study was to determine salivary levels of vascular endothelial growth factor (VEGF), interleukin (IL)-8, monocyte...

  6. 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.

  7. 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...

  8. Falsely Elevated Plasma Creatinine Due to an Immunoglobulin M Paraprotein.

    Science.gov (United States)

    McGill, Mitchell R; Vijayan, Anitha; Trulock, Elbert P; Witt, Chad A; Kohler, Giselle D; Scott, Mitchell G

    2016-11-01

    The most common method for measuring plasma creatinine is based on its reaction with picric acid. However, enzymatic methods are becoming more popular due to improved specificity. We present a case of falsely elevated plasma creatinine values obtained by an enzymatic method that turned out to be due to a monoclonal immunoglobulin M (IgM) paraprotein. A 63-year-old woman evaluated for lung transplantation had falsely increased plasma creatinine levels (1.54-1.71mg/dL; corresponding to estimated glomerular filtration rates of 32-36 mL/min/1.73m 2 ) as measured by the Roche Creatinine plus enzymatic assay when compared with the picric acid-based procedure and several other enzymatic methods, which gave plasma creatinine values of 0.7 to 0.8mg/dL. Serum protein electrophoresis revealed an IgM κ light chain paraprotein. Removal of high-molecular-weight (>30kDa) proteins by ultrafiltration reduced the patient's plasma creatinine level by the Roche enzymatic method to 0.7mg/dL. Addition of the patient's immunoglobulin fraction to plasma from other patients with normal plasma creatinine levels resulted in values that were increased by 0.58 to 0.62mg/dL. Furthermore, removal of non-IgM immunoglobulins with protein G-coupled beads did not eliminate the interference from the patient's plasma. Taken together, these studies demonstrate that falsely elevated plasma creatinine values by the Roche enzymatic method can be due to an IgM paraprotein. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  9. Enhancement of polymeric immunoglobulin receptor transcytosis by biparatopic VHH.

    Directory of Open Access Journals (Sweden)

    Chris D Emmerson

    Full Text Available The polymeric immunoglobulin receptor (pIgR ensures the transport of dimeric immunoglobulin A (dIgA and pentameric immunoglobulin M (pIgM across epithelia to the mucosal layer of for example the intestines and the lungs via transcytosis. Per day the human pIgR mediates the excretion of 2 to 5 grams of dIgA into the mucosa of luminal organs. This system could prove useful for therapies aiming at excretion of compounds into the mucosa. Here we investigated the use of the variable domain of camelid derived heavy chain only antibodies, also known as VHHs or Nanobodies®, targeting the human pIgR, as a transport system across epithelial cells. We show that VHHs directed against the human pIgR are able to bind the receptor with high affinity (∼1 nM and that they compete with the natural ligand, dIgA. In a transcytosis assay both native and phage-bound VHH were only able to get across polarized MDCK cells that express the human pIgR gene in a basolateral to apical fashion. Indicating that the VHHs are able to translocate across epithelia and to take along large particles of cargo. Furthermore, by making multivalent VHHs we were able to enhance the transport of the compounds both in a MDCK-hpIgR and Caco-2 cell system, probably by inducing receptor clustering. These results show that VHHs can be used as a carrier system to exploit the human pIgR transcytotic system and that multivalent compounds are able to significantly enhance the transport across epithelial monolayers.

  10. 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.

  11. Enhanced Human-Type Receptor Binding by Ferret-Transmissible H5N1 with a K193T Mutation.

    Science.gov (United States)

    Peng, Wenjie; Bouwman, Kim M; McBride, Ryan; Grant, Oliver C; Woods, Robert J; Verheije, Monique H; Paulson, James C; de Vries, Robert P

    2018-05-15

    All human influenza pandemics have originated from avian influenza viruses. Although multiple changes are needed for an avian virus to be able to transmit between humans, binding to human-type receptors is essential. Several research groups have reported mutations in H5N1 viruses that exhibit specificity for human-type receptors and promote respiratory droplet transmission between ferrets. Upon detailed analysis, we have found that these mutants exhibit significant differences in fine receptor specificity compared to human H1N1 and H3N2 and retain avian-type receptor binding. We have recently shown that human influenza viruses preferentially bind to α2-6-sialylated branched N-linked glycans, where the sialic acids on each branch can bind to receptor sites on two protomers of the same hemagglutinin (HA) trimer. In this binding mode, the glycan projects over the 190 helix at the top of the receptor-binding pocket, which in H5N1 would create a stearic clash with lysine at position 193. Thus, we hypothesized that a K193T mutation would improve binding to branched N-linked receptors. Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses. IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans. Fortunately, H5N1 viruses do not transmit between humans because they do not bind to human-type receptors. In 2012, three seminal papers have shown how these viruses can be engineered to transmit between ferrets, the human model for influenza virus infection. Receptor binding, among others, was changed, and the viruses now bind to human-type receptors. Receptor specificity was still markedly different compared to that of human influenza viruses. Here we report an additional mutation in ferret

  12. Differentiating immunoglobulin g4-related sclerosing cholangitis from hilar cholangiocarcinoma.

    Science.gov (United States)

    Tabata, Taku; Kamisawa, Terumi; Hara, Seiichi; Kuruma, Sawako; Chiba, Kazuro; Kuwata, Go; Fujiwara, Takashi; Egashira, Hideto; Koizumi, Koichi; Fujiwara, Junko; Arakawa, Takeo; Momma, Kumiko; Kurata, Masanao; Honda, Goro; Tsuruta, Koji; Itoi, Takao

    2013-03-01

    Few studies have differentiated immunoglobulin G (IgG) 4-related sclerosing cholangitis (IgG4-SC) from hilar cholangiocarcinoma (CC). Thus, we sought to investigate useful features for differentiating IgG4-SC from hilar CC. We retrospectively compared clinical, serological, imaging, and histological features of six patients with IgG4-SC and 42 patients with hilar CC. In patients with hilar CC, obstructive jaundice was more frequent (philar CC patients (philar or hepatic duct was completely obstructed in 83% of hilar CC patients (philar bile duct stenosis, was more frequent in IgG4-SC patients (philar CC.

  13. Gm typing by immunoglobulin heavy-chain gene RFLP analysis.

    OpenAIRE

    Jazwinska, E C; Dunckley, H; Propert, D N; Gatenby, P A; Serjeantson, S W

    1988-01-01

    This study was undertaken to investigate a means of assigning Gm allotypes to Caucasians by RFLP analysis. A single immunoglobulin heavy-chain gamma-4 cDNA probe (HU gamma 4) was hybridized with genomic DNA digested separately with two restriction enzymes, TaqI and PvuII. Results showed excellent correlation (P less than .001) between serologically defined Gm allotypes G1m(1), G1m(2), G2m(23), and G1m;G3m (3;5,10) and RFLPs identified with the (HU gamma 4) probe. We conclude that it is now po...

  14. 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...... with NSTI 1:1 to masked infusion of 25 g of IVIG (Privigen, CSL Behring) or an equal volume of 0.9% saline once daily for the first 3 days of ICU admission. The primary outcome was the physical component summary (PCS) score of the 36-item short form health survey (SF-36) 6 months after randomisation...

  15. Use of [75Se]selenomethionine in immunoglobulin biosynthetic studies

    International Nuclear Information System (INIS)

    Gutman, G.A.; Warner, N.L.; Harris, A.W.; Bowles, A.

    1978-01-01

    The gamma-emitting amino acid analog, [ 75 Se] selenomethionine, has been used as a biosynthetic label for immunoglobulins secreted by plasmacytomas in tissue culture. The secreted products are structurally intact with respect to their antibody combining sites and their class and allotype antigenic specificities. A component of [ 75 Se] selenomethionine preparations was found to bind to fetal calf serum proteins, in a manner releasable by mercaptoethanol, but not by sodium dodecyl sulfate and urea. Methods for circumventing the problems caused by this binding are described. (Auth.)

  16. Malacoplakia associated with vesicoureteral reflux and selective immunoglobulin A deficiency.

    Science.gov (United States)

    Witherington, R; Branan, W J; Wray, B B; Best, G K

    1984-11-01

    A case of malacoplakia involving the lower urinary tract of a young black boy, with associated bilateral vesicoureteral reflux, hydronephrosis and selective immunoglobulin A deficiency is reported. Reflux was caused by the malacoplakia. Reflux and hydronephrosis persisted despite elimination of bacterial infection and malacoplakia by drug therapy. These abnormalities were corrected by a conventional antireflux operation. Malacoplakia appears to be related to immunologic incompetence and diminished levels of intracellular cyclic 3',5' guanine monophosphate. Cholinergic agonists reverse or prevent the pathological changes of malacoplakia.

  17. 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

    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 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. 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. PMID:25667732

  18. INFLUENCE OF HIGH CORTISOL DOSES UPON THE SERUM IMMUNOGLOBULIN LEVEL

    OpenAIRE

    Voja Pavlovic; Zoran Pavlovic

    2001-01-01

    The effects of Cortisol upon the serum immunoglobulin concentration areexamined. The experiment involved male guinea pigs of the body weight from 300 to400 g that were nonnally fed and lived under the common laboratory conditions. Theguinea pigs were divided into an experimental and a control group. The experimentalgroup's guinea pigs were given every day (in a 6 days' period) a subcutaneous dose of80 g of corti sol/kg/per day, while the control group ones were given only one ml ofthe physiol...

  19. Grave's disease associated with immunoglobulin A nephropathy: A rare association.

    Science.gov (United States)

    Khan, I; Bhat, R A; Khan, I; Hameed, I

    2015-01-01

    Immunoglobulin A (Ig A) nephropathy is the most common form of primary glomerulonephritis. The association of Ig A nephropathy with Grave's disease has not been reported so far. We report a case of 20-year-old female with Grave's disease who presented with edema, facial puffiness, and decreased urine output. She was found to be hypertensive with renal failure and nephrotic range proteinuria. Renal biopsy revealed features of Ig A nephropathy. The patient was treated with oral corticosteroids (1 mg/kg/day). To our knowledge, this is the first case showing association of Grave's disease with Ig A nephropathy.

  20. Visceral adiposity is associated with cytokines and decrease in lung function in women with persistent asthma

    Directory of Open Access Journals (Sweden)

    A.V. Capelo

    2016-09-01

    Full Text Available Abdominal obesity is associated with a risk of cardiovascular diseases, metabolic syndrome and decreased lung function. However, it is not known whether asthma control is influenced by the accumulation of adipose tissue in the various abdominal compartments. Objective: To determine associations among abdominal adiposity distribution, asthma control, lung function and cytokines in women. Methods and design: In this cross-sectional study of asthmatic women, data on demographic variables, comorbid conditions, disease history, anthropometric and spirometric measurements were collected. Subcutaneous (SAT and visceral (VAT adipose tissues were measured by ultrasound, and the steatosis level was obtained. Asthma control was assessed according to Global Initiative for Asthma (GINA criteria. Atopy was defined on the basis of allergen-specific Immunoglobulin E and/or skin prick testing. Cytokine levels were determined using enzyme-linked immunosorbant assays (ELISAs. Results: Eighty-three asthmatic women were included, 37% of whom had uncontrolled asthma. After controlling for variables, a negative association between asthma control and VAT and the VAT/SAT ratio was observed. VAT was negatively associated with respiratory parameters after controlling for explanatory variables. In an adjusted model, body mass index (BMI and SAT were inversely associated with the adiponectin serum level and VAT was associated with the interleukin 6 level. In conclusion, visceral obesity was negatively associated with asthma control and lung function; and positively associated with increased levels of interleukin 6 in women. We hypothesize that women should be studied as a separate group, and we suggest further studies with a control group to know if the uncontrolled asthmatic group is directly affected by visceral adipose inflammatory markers. Keywords: Asthma, Woman, Abdominal obesity, Lung function, Cytokines, Asthma control

  1. Evaluation of adsorption selectivity of immunoglobulins M, A and G and purification of immunoglobulin M with mixed-mode resins.

    Science.gov (United States)

    Luo, Ying-Di; Zhang, Qi-Lei; Yao, Shan-Jing; Lin, Dong-Qiang

    2018-01-19

    This study investigated adsorption selectivity of immunoglobulin M (IgM), immunoglobulin A (IgA) and immunoglobulin (IgG) on four mixed-mode resins with the functional ligands of 4-mercatoethyl-pyridine (MEP), 2-mercapto-1-methylimidazole (MMI), 5-aminobenzimidazole (ABI) and tryptophan-5-aminobenzimidazole (W-ABI), respectively. IgM purification processes with mixed-mode resins were also proposed. All resins showed typical pH-dependent adsorption, and high adsorption capacity was found at pH 5.0-8.0 with low adsorption capacity under acidic conditions. Meanwhile, high selectivity of IgM/IgA and IgM/IgG was obtained with ABI-4FF and MMI-4FF resins at pH 4.0-5.0, which was used to develop a method for IgM, IgA and IgG separation by controlling loading and elution pH. Capture of monoclonal IgM from cell culture supernatant with ABI-4FF resins was studied and high purity (∼99%) and good recovery (80.8%) were obtained. Moreover, IgM direct separation from human serum with combined two-step chromatography (ABI-4FF and MMI-4FF) was investigated, and IgM purity of 65.2% and a purification factor of 28.3 were obtained after optimization. The antibody activity of IgM was maintained after purification. The results demonstrated that mixed-mode chromatography with specially-designed ligands is a promising way to improve adsorption selectivity and process efficiency of IgM purification from complex feedstock. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. 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

  3. Cytokines and Organ Failure in Acute Pancreatitis

    DEFF Research Database (Denmark)

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

    2012-01-01

    Objectives: 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). Methods: Interleukin (IL) 6, IL-8, IL-18, and tumor necrosis factor > were measured on admission...

  4. 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 ...

  5. 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

  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. 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

  8. Proinflammatory cytokines in open versus laparoscopic cholecystectomy

    International Nuclear Information System (INIS)

    Abu-Eshy, Saeed A.; Al-Rofaidi, Abdallah A.; Al-Faki, Ahmed S.; Ghalib, Hashim W.; Moosa, Riyadh A.; Sadik, Ali A.; Salati, Mohammad I.

    2002-01-01

    Laparoscopic cholecystectomy, a minimal access surgery, is fast replacing open cholecystectomy and is being associated with less trauma. The objective of this study was to compare the proinflammatory cytokine levels in both laparoscopic cholecystectomy and open cholecystectomy. This study was carried out at Aseer Central Hospital, Aseer region, Abha Private Hospital and the College of Medicine and Medical Sciences, King Khalid University, Abha, Kingdom of Saudi Arabia, during the time period October 1998 through to November 2000. Sixty-one patients were included in the study, 27 of them had laparoscopic cholecystectomy and 34 had open cholecystectomy. Cytokines [Interleukin-6 Interleukin-1b, Tumor necrosis factor -a and Interleukin- 8] were measured in blood samples collected from the patients before, at and 24 hours post surgery, using commercially available kits. Interleukin-6 levels were significantly increased at 24 hours post surgery in the open cholecystectomy group of patients compared to the laparoscopic cholecystectomy group (P<0.04). No differences were found in the other cytokines levels (Interleukin-1b, tumor necrosis factor -a and Interleukin-8) between the open cholecystectomy and laparoscopic cholecystectomy groups. Laparoscopic cholecystectomy, a minimal access surgery, is associated with lower levels of the proinflammatory interleukin-6 cytokine compared to open cholecystectomy. (author)

  9. 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.

  10. 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

  11. Immunoglobulins in the eggs of the nurse shark, Ginglymostoma cirratum.

    Science.gov (United States)

    Haines, Ashley N; Flajnik, Martin F; Rumfelt, Lynn L; Wourms, John P

    2005-01-01

    Elasmobranchs, which include the sharks, skates, and rays, emerged over 450 million years ago and are the oldest vertebrates to possess an adaptive immune system. They have evolved diverse reproductive modes, with a variety of physiological adaptations that enhance reproductive success. The nurse shark, Ginglymostoma cirratum, is an aplacental, viviparous elasmobranch in which the egg and its associated vitelline vasculature are the primary route for maternal-embryonic interactions. During gestation, nurse shark embryos hatch from their eggcases and develop free in the uterus, which is flushed regularly with seawater. Similar to higher vertebrates, embryonic and neonatal nurse sharks possess an immune system that is not fully competent. In birds and bony fishes, maternal immunoglobulins (Ig) stored in the egg during oogenesis confer protective immunity to embryos during gestation. However, early research suggested that such transfer of passive immunity does not occur in sharks. To better understand how elasmobranch embryos are protected from waterborne pathogens during this potentially vulnerable time, we have re-examined the existence of Igs in elasmobranch eggs. Using monoclonal antibodies, we establish the presence of two classes of Igs in nurse shark eggs: 7S IgM and IgNAR. The potential transfer of immunoglobulins from elasmobranch eggs is discussed.

  12. Immunoglobulins and C3 in the P. brasiliensis granuloma

    Directory of Open Access Journals (Sweden)

    Lilian M. V. Biagioni

    1987-04-01

    Full Text Available The experimental model of paracoccidioidomycosis induced in mice by the intravenous injection of yeast-forms of P. brasiliensis (Bt2 strain; 1 x 10(6 viable fungi/animal was used to evaluate sequentially 2, 4, 8, 16 and 20 weeks after inoculation: 1. The presence of immunoglobulins and C3 in the pulmonary granuloma-ta, by direct immunofluorescence; 2. The humoral (immunodiffusion test and the cellular (footpad sweeling test immune response; 3. The histopathology of lesions. The cell-immune response was positive since week 2, showing a transitory depression at week 16. Specific antibodies were first detected at week 4 and peaked at week 16. At histology, epithelioid granulomas with numerous fungi and polymorphonuclear agreggates were seen. The lungs showed progressive involvement up to week 16, with little decrease at week 20. From week 2 on, there were deposits of IgG and C3 around fungal walls within the granulomas and IgG stained cells among the mononuclear cell peripheral halo. Interstitital immunoglobulins and C3 deposits in the granulomas were not letected. IgG and C3 seen to play an early an important role in. the host defenses against P. brasiliensis by possibly cooperating in the killing of parasites and blocking the antigenic diffusion.

  13. Autoantibodies and immunoglobulins among atomic-bomb survivors

    International Nuclear Information System (INIS)

    Fujiwara, Saeko; Carter, R.L.; Akiyama, Mitoshi

    1993-06-01

    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 2061 Adult Health Study participants in Hiroshima and Nagasaki from December 1987 to November 1989. The prevalence and titers of rheumatoid factor increased in a statistically significant manner with increasing radiation dose. No radiation effect was found on the prevalence of antinuclear antibody, antithyroglobulin antibody, and anti-thyroid-microsomal antibody. A statistically significant relationship was also found between radiation exposure and the IgA level in females and the IgM levels in both sexes-both levels increased as radiation dose increased. However, the effects of radiation exposure were not large and accounted for less than 10% of the total variation in each measurement. Levels of IgG and IgE were not affected by radiation exposure. (author)

  14. Risk factors for venous thromboembolism in immunoglobulin light chain amyloidosis.

    Science.gov (United States)

    Bever, Katherine M; Masha, Luke I; Sun, Fangui; Stern, Lauren; Havasi, Andrea; Berk, John L; Sanchorawala, Vaishali; Seldin, David C; Sloan, J Mark

    2016-01-01

    Patients with immunoglobulin light chain amyloidosis are at risk for both thrombotic and bleeding complications. While the hemostatic defects have been extensively studied, less is known about thrombotic complications in this disease. This retrospective study examined the frequency of venous thromboembolism in 929 patients with immunoglobulin light chain amyloidosis presenting to a single referral center, correlated risk of venous thromboembolism with clinical and laboratory factors, and examined complications of anticoagulation in this population. Sixty-five patients (7%) were documented as having at least one venous thromboembolic event. Eighty percent of these patients had events within one year prior to or following diagnosis. Lower serum albumin was associated with increased risk of VTE, with a hazard ratio of 4.30 (CI 1.60-11.55; P=0.0038) for serum albumin less than 3 g/dL compared to serum albumin greater than 4 g/dL. Severe bleeding complications were observed in 5 out of 57 patients with venous thromboembolism undergoing treatment with anticoagulation. Prospective investigation should be undertaken to better risk stratify these patients and to determine the optimal strategies for prophylaxis against and management of venous thromboembolism. Copyright© Ferrata Storti Foundation.

  15. Killer Cell Immunoglobulin-like Receptors and their Ligands

    Directory of Open Access Journals (Sweden)

    Tajik N.

    2010-09-01

    Full Text Available The Natural killer (NK cells are a subset of lymphocytes comprising around 10% of total lymphocytes in peripheral blood. Due to their role in the innate response, NK cells provide a ‘first line of defense’ against infectious agents and cancer and are also thought to play a role in autoimmunity. The killer cell immunoglobulin-like receptors (KIR are regulatory surface molecules, found on NK cells and on a subset of T lymphocytes. The genes for KIR are present on chromosome 19 in the leukocyte receptor complex and show a major difference for both the type and number of KIR genes present among different ethnic groups. They have been divided into two groups of 2D or 3D, depending on the number of external immunoglobulin domains. The presence of a long cytoplasmic tail with two immune tyrosine-based inhibitory motifs (ITIM allows the transduction of inhibitory signals and characterizes the inhibitory KIRs (2DL and 3DL, whereas the presence of short cytoplasmic tails corresponds to the activating KIR receptors (2DS and 3DS.These polymorphic receptors interact with specific motifs on human leukocyte antigen (HLA class I molecules, modulate NK cytolytic activity. Some KIRs are known to interact with HLA-C molecules of target cells, HLA-Bw4 molecules and HLA-A3/11. For some KIRs the corresponding ligands are still unknown.

  16. Cytomegalovirus neutralization by hyperimmune and standard intravenous immunoglobulin preparations.

    Science.gov (United States)

    Planitzer, Christina B; Saemann, Marcus D; Gajek, Hartwig; Farcet, Maria R; Kreil, Thomas R

    2011-08-15

    Cytomegalovirus (CMV) remains one of the most important pathogens after transplantation, potentially leading to CMV disease, allograft dysfunction, acute, and chronic rejection and opportunistic infections. Immunoglobulin G (IgG) preparations with high antibody titers against CMV are a valuable adjunctive prevention and treatment option for clinicians and apart from standard intravenous immunoglobulin (IVIG), CMV hyperimmune preparations are available. The CMV antibody titer of these preparations is typically determined by Enzyme-linked immunosorbent assay (ELISA), also used for the selection of high titer plasma donors for the production of the CMV Hyperimmune product. However, CMV ELISA titers do not necessarily correlate with CMV antibody function which is determined by virus neutralization tests. CMV antibody titers were determined by both ELISA and virus neutralization assay and the IgG subclass distribution was compared between a CMV hyperimmune licensed in Europe and standard IVIG preparations. Although the expected high CMV IgG ELISA antibody titers were confirmed for three lots of a CMV hyperimmune preparation, the functionally more relevant CMV neutralizing antibody titers were significantly higher for 31 lots of standard IVIG preparations. Moreover, considerably lower IgG3 levels were found for the CMV hyperimmune preparation compared with standard IVIG preparations. The higher functional CMV neutralization titers of standard IVIG preparations and the better availability of these preparations, suggest that these products could be a valuable alternative to the CMV hyperimmune preparation.

  17. Risk factors for venous thromboembolism in immunoglobulin light chain amyloidosis

    Science.gov (United States)

    Bever, Katherine M.; Masha, Luke I.; Sun, Fangui; Stern, Lauren; Havasi, Andrea; Berk, John L.; Sanchorawala, Vaishali; Seldin, David C.; Sloan, J. Mark

    2016-01-01

    Patients with immunoglobulin light chain amyloidosis are at risk for both thrombotic and bleeding complications. While the hemostatic defects have been extensively studied, less is known about thrombotic complications in this disease. This retrospective study examined the frequency of venous thromboembolism in 929 patients with immunoglobulin light chain amyloidosis presenting to a single referral center, correlated risk of venous thromboembolism with clinical and laboratory factors, and examined complications of anticoagulation in this population. Sixty-five patients (7%) were documented as having at least one venous thromboembolic event. Eighty percent of these patients had events within one year prior to or following diagnosis. Lower serum albumin was associated with increased risk of VTE, with a hazard ratio of 4.30 (CI 1.60–11.55; P=0.0038) for serum albumin less than 3 g/dL compared to serum albumin greater than 4 g/dL. Severe bleeding complications were observed in 5 out of 57 patients with venous thromboembolism undergoing treatment with anticoagulation. Prospective investigation should be undertaken to better risk stratify these patients and to determine the optimal strategies for prophylaxis against and management of venous thromboembolism. PMID:26452981

  18. Curcumin suppression of cytokine release and cytokine storm. A potential therapy for patients with Ebola and other severe viral infections.

    Science.gov (United States)

    Sordillo, Peter P; Helson, Lawrence

    2015-01-01

    The terminal stage of Ebola and other viral diseases is often the onset of a cytokine storm, the massive overproduction of cytokines by the body's immune system. The actions of curcumin in suppressing cytokine release and cytokine storm are discussed. Curcumin blocks cytokine release, most importantly the key pro-inflammatory cytokines, interleukin-1, interleukin-6 and tumor necrosis factor-α. The suppression of cytokine release by curcumin correlates with clinical improvement in experimental models of disease conditions where a cytokine storm plays a significant role in mortality. The use of curcumin should be investigated in patients with Ebola and cytokine storm. Intravenous formulations may allow achievement of therapeutic blood levels of curcumin. Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  19. Recombinant canine distemper virus strain Snyder Hill expressing green or red fluorescent proteins causes meningoencephalitis in the ferret.

    Science.gov (United States)

    Ludlow, M; Nguyen, D T; Silin, D; Lyubomska, O; de Vries, R D; von Messling, V; McQuaid, S; De Swart, R L; Duprex, W P

    2012-07-01

    The propensity of canine distemper virus (CDV) to spread to the central nervous system is one of the primary features of distemper. Therefore, we developed a reverse genetics system based on the neurovirulent Snyder Hill (SH) strain of CDV (CDV(SH)) and show that this virus rapidly circumvents the blood-brain and blood-cerebrospinal fluid (CSF) barriers to spread into the subarachnoid space to induce dramatic viral meningoencephalitis. The use of recombinant CDV(SH) (rCDV(SH)) expressing enhanced green fluorescent protein (EGFP) or red fluorescent protein (dTomato) facilitated the sensitive pathological assessment of routes of virus spread in vivo. Infection of ferrets with these viruses led to the full spectrum of clinical signs typically associated with distemper in dogs during a rapid, fatal disease course of approximately 2 weeks. Comparison with the ferret-adapted CDV(5804P) and the prototypic wild-type CDV(R252) showed that hematogenous infection of the choroid plexus is not a significant route of virus spread into the CSF. Instead, viral spread into the subarachnoid space in rCDV(SH)-infected animals was triggered by infection of vascular endothelial cells and the hematogenous spread of virus-infected leukocytes from meningeal blood vessels into the subarachnoid space. This resulted in widespread infection of cells of the pia and arachnoid mater of the leptomeninges over large areas of the cerebral hemispheres. The ability to sensitively assess the in vivo spread of a neurovirulent strain of CDV provides a novel model system to study the mechanisms of virus spread into the CSF and the pathogenesis of acute viral meningitis.

  20. Effects of zacopride and BMY25801 (batanopride) on radiation-induced emesis and locomotor behavior in the ferret

    International Nuclear Information System (INIS)

    King, G.L.; Landauer, M.R.

    1990-01-01

    The antiemetic and locomotor effects of two substituted benzamides, zacopride and batanopride (BMY25801), were compared in ferrets after bilateral 60Co irradiation at 2, 4 or 6 Gy. Both zacopride and BMY25801 were effective against emesis and related signs. Zacopride, tested at several doses (0.003, 0.03 and 0.3 mg/kg), appeared to be more potent because it abolished emesis at 100-fold lower doses than did BMY25801 (3 mg/kg). The ED50 value for the antiemetic effect of zacopride was 0.026 mg/kg (confidence levels = 0.0095, 0.072 mg/kg). However, analysis of emetic parameters recorded from vomiting animals (e.g., latency to first emesis) demonstrated that BMY25801 provided greater antiemetic protection in this population than zacopride without any apparent side effects. Locomotor activity was significantly depressed by both radiation (all doses) and zacopride alone (0.03 mg/kg and 0.3 mg/kg). BMY25801 alone did not affect locomotor activity, and protected against the radiation-induced locomotor decrement. Although zacopride potentiated the locomotor decrement to radiation, no clear dose-response relationship was evident. Bilateral abdominal vagotomy significantly increased the latency to the first emetic episode and significantly reduced the number of retches, but did not alter the duration of the prodromal response to 4-Gy irradiation. Unilateral vagotomies had no effect. Zacopride (at 0.03 mg/kg and 0.3 mg/kg) remained an effective antiemetic in animals that received a bilateral vagotomy, abolishing emesis in four of eight and two of eight ferrets, respectively. These data suggest that the antiemetic action of zacopride does not fully depend on intact vagal innervation and also acts via other pathways

  1. Neuropathic pain and cytokines: current perspectives

    Directory of Open Access Journals (Sweden)

    Clark AK

    2013-11-01

    Full Text Available Anna K Clark, Elizabeth A Old, Marzia Malcangio Wolfson Centre for Age Related Diseases, King's College London, London, UK Abstract: Neuropathic pain represents a major problem in clinical medicine because it causes debilitating suffering and is largely resistant to currently available analgesics. A characteristic of neuropathic pain is abnormal response to somatic sensory stimulation. Thus, patients suffering peripheral neuropathies may experience pain caused by stimuli which are normally nonpainful, such as simple touching of the skin or by changes in temperature, as well as exaggerated responses to noxious stimuli. Convincing evidence suggests that this hypersensitivity is the result of pain remaining centralized. In particular, at the first pain synapse in the dorsal horn of the spinal cord, the gain of neurons is increased and neurons begin to be activated by innocuous inputs. In recent years, it has become appreciated that a remote damage in the peripheral nervous system results in neuronal plasticity and changes in microglial and astrocyte activity, as well as infiltration of macrophages and T cells, which all contribute to central sensitization. Specifically, the release of pronociceptive factors such as cytokines and chemokines from neurons and non-neuronal cells can sensitize neurons of the first pain synapse. In this article we review the current evidence for the role of cytokines in mediating spinal neuron–non-neuronal cell communication in neuropathic pain mechanisms following peripheral nerve injury. Specific and selective control of cytokine-mediated neuronal–glia interactions results in attenuation of the hypersensitivity to both noxious and innocuous stimuli observed in neuropathic pain models, and may represent an avenue for future therapeutic intervention. Keywords: anti-inflammatory cytokines, proinflammatory cytokines, microglia, astrocytes, first pain synapse

  2. 21 CFR 866.5550 - Immunoglobulin (light chain specific) immunological test system.

    Science.gov (United States)

    2010-04-01

    ... of antibody-forming cells), lymphocytic neoplasms (cancer of lymphoid tissue), Waldenstrom's macroglobulinemia (increased production of large immunoglobulins), and connective tissue diseases such as rheumatoid... portions of immunoglobulin molecules in serum, other body fluids, and tissues. In some disease states, an...

  3. Characterization of immunoglobulin A kappa autoantibodies to human lactate dehydrogenase isoenzyme-3

    NARCIS (Netherlands)

    Weijers, R. N.; Oude Elferink, R. P.; Mulder, J.; Kruijswijk, H.

    1987-01-01

    We have purified with a cumulative recovery of 48% from the serum of a patient the immunoglobulin A kappa subunit of the lactate dehydrogenase-immunoglobulin A kappa (LD-IgA kappa) complex. It appears that the pI range of the complex is 5.4-5.8. The Ig part of the complex showed a monoclonal

  4. Evaluation of immunoglobulin G synthesizing plasma cells in periapical granuloma and cyst.

    OpenAIRE

    Grover N; Rao N; Kotian M

    2001-01-01

    Immunoglobulin synthesizing plasma cells for IgG were quantitated in 20 periapical granulomas and 20 periapical cysts, using unlabelled antibody peroxidase-antiperoxidase complex method. Result showed that immunoglobulin G producing plasma cells were predominant in periapical cyst as compared with periapical granuloma. A statistical significant relation was observed between these two lesions.

  5. Differential production of immunoglobulin classes and subclasses by mucosal-type human B-lymphocytes exposed in vitro to CpG oligodeoxynucleotides.

    Science.gov (United States)

    Cognasse, Fabrice; Acquart, Sophie; Beniguel, Lydie; Sabido, Odile; Chavarin, Patricia; Genin, Christian; Garraud, Olivier

    2005-01-01

    As B-lymphocytes play an important role in innate and adaptive immunity, we aimed to examine the effects of CpG oligodeoxynucleotides (ODNs) on purified tonsil-originating CD19+ B-cells, representing mucosal B-cells. We screened various K-type ODNs, reactive with human B-cells, and tested for the production of immunoglobulins in vitro. Using one CpG-ODN, DSP30, we observed that it could upregulate not only Toll-like receptor 9 (TLR9) mRNA expression in activated B-cells, but also the early expression of CD69 followed by the sequential expression of CD80, CD86 and the nuclear factor (NF)-kappaB pathway. Furthermore, mRNA expression of certain B-cell-derived cytokines was influenced by exposure to DSP30, with a strong upregulation of interleukin 6 (IL-6) and downregulation of IL1-beta. Stimulation of B-cells, co-stimulated with IL-2, IL-10 and soluble CD40 ligand (sCD40L) with different CpG-ODNs, had differing effects on the terminal differentiation in vitro of B-cells into immunoglobulin-secreting cells. TLR9 is involved in innate immunity and the recognition of bound CpG DNA from invading bacterial pathogens. As tonsillar B-cells are mucosal-type B-lymphocytes, this study suggests that CpG-ODNs show promise as mucosal adjuvants in modulating the local production of immunoglobulins of certain classes and subclasses, a crucial issue in vaccine perspectives.

  6. Circulating immune complexes, immunoglobulin G, salivary proteins and salivary immunoglobulin A in patients with Sjögren's syndrome

    Directory of Open Access Journals (Sweden)

    Hadži-Mihailović Miloš

    2009-01-01

    Full Text Available Introduction. Sjögren's syndrome (SS is a chronic autoimmune disorder, with its major clinical manifestations resulting from changes in exocrine glands. Objective The aim of this study was to evaluate serum concentrations of circulating immune complexes (CIC and immunoglobulin G (IgG, and salivary proteins (SP and salivary immunoglobulin A (sIgA in 40 patients with SS, and to correlate these values among themselves, as well as with the unstimulated salivary flow rate (USFR and the duration of disease. Methods. The total of 40 patients were included in this research. CIC was determined using the solution of polyethylene glycol and IgG with the standard procedure of radial immunodiffusion. SP was investigated by the method of Lowry and sIgA was separated from the whole saliva using the method of immune chromatography. Results. The values of most of the studied parameters exceeded the normal range in a high degree: CIC 72.5%, IgG 70%, SP 80%. The concentrations of CIC were significantly higher in the patients with the duration of disease less than 10 years. With the decrease of USFR, the concentration of sIgA and IgG were increased with statistical significance. Conclusion The increased prevalence of abnormal values of CIC, IgG and SP indicate that the patients with SS have developed a higher level of immune reactivity. These results could be useful in diagnosis and disease activity monitoring.

  7. Follicular B Cells Promote Atherosclerosis via T Cell-Mediated Differentiation Into Plasma Cells and Secreting Pathogenic Immunoglobulin G.

    Science.gov (United States)

    Tay, Christopher; Liu, Yu-Han; Kanellakis, Peter; Kallies, Axel; Li, Yi; Cao, Anh; Hosseini, Hamid; Tipping, Peter; Toh, Ban-Hock; Bobik, Alex; Kyaw, Tin

    2018-05-01

    B cells promote or protect development of atherosclerosis. In this study, we examined the role of MHCII (major histocompatibility II), CD40 (cluster of differentiation 40), and Blimp-1 (B-lymphocyte-induced maturation protein) expression by follicular B (FO B) cells in development of atherosclerosis together with the effects of IgG purified from atherosclerotic mice. Using mixed chimeric Ldlr -/- mice whose B cells are deficient in MHCII or CD40, we demonstrate that these molecules are critical for the proatherogenic actions of FO B cells. During development of atherosclerosis, these deficiencies affected T-B cell interactions, germinal center B cells, plasma cells, and IgG. As FO B cells differentiating into plasma cells require Blimp-1, we also assessed its role in the development of atherosclerosis. Blimp-1-deficient B cells greatly attenuated atherosclerosis and immunoglobulin-including IgG production, preventing IgG accumulation in atherosclerotic lesions; Blimp-1 deletion also attenuated lesion proinflammatory cytokines, apoptotic cell numbers, and necrotic core. To determine the importance of IgG for atherosclerosis, we purified IgG from atherosclerotic mice. Their transfer but not IgG from nonatherosclerotic mice into Ldlr -/- mice whose B cells are Blimp-1-deficient increased atherosclerosis; transfer was associated with IgG accumulating in atherosclerotic lesions, increased lesion inflammatory cytokines, apoptotic cell numbers, and necrotic core size. The mechanism by which FO B cells promote atherosclerosis is highly dependent on their expression of MHCII, CD40, and Blimp-1. FO B cell differentiation into IgG-producing plasma cells also is critical for their proatherogenic actions. Targeting B-T cell interactions and pathogenic IgG may provide novel therapeutic strategies to prevent atherosclerosis and its adverse cardiovascular complications. © 2018 American Heart Association, Inc.

  8. A proton nuclear magnetic resonance-based metabonomics study of metabolic profiling in immunoglobulin a nephropathy

    International Nuclear Information System (INIS)

    Sui, Weiguo; Che, Wenti; Guimai, Zuo; Chen, Jiejing; Li, Liping; Li, Wuxian; Dai, Yong

    2012-01-01

    Objectives: Immunoglobulin A nephropathy is the most common cause of chronic renal failure among primary glomerulonephritis patients. The ability to diagnose immunoglobulin A nephropathy remains poor. However, renal biopsy is an inconvenient, invasive, and painful examination, and no reliable biomarkers have been developed for use in routine patient evaluations. The aims of the present study were to identify immunoglobulin A nephropathy patients, to identify useful biomarkers of immunoglobulin A nephropathy and to establish a human immunoglobulin A nephropathy metabolic profile. Methods: Serum samples were collected from immunoglobulin A nephropathy patients who were not using immunosuppressants. A pilot study was undertaken to determine disease-specific metabolite biomarker profiles in three groups: healthy controls (N = 23), low-risk patients in whom immunoglobulin A nephropathy was confirmed as grades I-II by renal biopsy (N = 23), and high-risk patients with nephropathies of grades IV-V (N = 12). Serum samples were analyzed using proton nuclear magnetic resonance spectroscopy and by applying multivariate pattern recognition analysis for disease classification. Results: Compared with the healthy controls, both the low-risk and high-risk patients had higher levels of phenylalanine, myo-inositol, lactate, L6 lipids ( CH-CH 2 -CH = O), L5 lipids (-CH 2 -C = O), and L3 lipids (-CH 2 -CH 2 -C = O) as well as lower levels of β-glucose, α-glucose, valine, tyrosine, phosphocholine, lysine, isoleucine, glycerolphosphocholine, glycine, glutamine, glutamate, alanine, acetate, 3-hydroxybutyrate, and 1-methylhistidine. Conclusions: These metabolites investigated in this study may serve as potential biomarkers of immunoglobulin A nephropathy. Point scoring of pattern recognition analysis was able to distinguish immunoglobulin A nephropathy patients from healthy controls. However, there were no obvious differences between the low-risk and high-risk groups in our research

  9. A proton nuclear magnetic resonance-based metabonomics study of metabolic profiling in immunoglobulin a nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Sui, Weiguo; Che, Wenti; Guimai, Zuo; Chen, Jiejing [181st Hospital Guangxi, Central Laboratory, Laboratory of Metabolic Diseases Research, Guangxi Province (China); Li, Liping [Guangxi Normal University, The Life Science College, Guangxi Province (China); Li, Wuxian [Key Laboratory of Laboratory Medical Diagnostics of Education Ministry, Chongqiong Medical University, Chongqing (China); Dai, Yong [Clinical Medical Research Center, the Second Clinical Medical College of Jinan University (Shenzhen People' s Hospital), Shenzhen, Guangdong Province (China)

    2012-07-01

    Objectives: Immunoglobulin A nephropathy is the most common cause of chronic renal failure among primary glomerulonephritis patients. The ability to diagnose immunoglobulin A nephropathy remains poor. However, renal biopsy is an inconvenient, invasive, and painful examination, and no reliable biomarkers have been developed for use in routine patient evaluations. The aims of the present study were to identify immunoglobulin A nephropathy patients, to identify useful biomarkers of immunoglobulin A nephropathy and to establish a human immunoglobulin A nephropathy metabolic profile. Methods: Serum samples were collected from immunoglobulin A nephropathy patients who were not using immunosuppressants. A pilot study was undertaken to determine disease-specific metabolite biomarker profiles in three groups: healthy controls (N = 23), low-risk patients in whom immunoglobulin A nephropathy was confirmed as grades I-II by renal biopsy (N = 23), and high-risk patients with nephropathies of grades IV-V (N = 12). Serum samples were analyzed using proton nuclear magnetic resonance spectroscopy and by applying multivariate pattern recognition analysis for disease classification. Results: Compared with the healthy controls, both the low-risk and high-risk patients had higher levels of phenylalanine, myo-inositol, lactate, L6 lipids ( CH-CH{sub 2}-CH = O), L5 lipids (-CH{sub 2}-C = O), and L3 lipids (-CH{sub 2}-CH{sub 2}-C = O) as well as lower levels of {beta}-glucose, {alpha}-glucose, valine, tyrosine, phosphocholine, lysine, isoleucine, glycerolphosphocholine, glycine, glutamine, glutamate, alanine, acetate, 3-hydroxybutyrate, and 1-methylhistidine. Conclusions: These metabolites investigated in this study may serve as potential biomarkers of immunoglobulin A nephropathy. Point scoring of pattern recognition analysis was able to distinguish immunoglobulin A nephropathy patients from healthy controls. However, there were no obvious differences between the low-risk and high

  10. Cytokine Correlations in Youth with Tic Disorders

    Science.gov (United States)

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

    2015-01-01

    Abstract 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. Methods: Twenty-one patients, ages 4–17 years (average 10.63±2.34 years, 13 males), with a clinical diagnosis of Tourette's syndrome (TS) or chronic tic disorder (CTD), were selected based on having clinic visits that coincided with a tic symptom exacerbation and a remission. Ratings of tic severity were assessed using the Yale Global Tic Severity Scale (YGTSS) and serum cytokine levels (interleukin [IL]-2, IL-4, IL-5, IL-10, IL-12p70, IL-13, interferon [IFN]-γ, tumor necrosis factor [TNF]-α, and granulocyte macrophage-colony stimulating factor [GM-CSF]) were measured using Luminex xMAP technology. Results: During tic symptom exacerbation, patients had higher median serum TNF-α levels (z=−1.962, p=0.05), particularly those on antipsychotics (U=9.00, p=0.033). Increased IL-13 was also associated with antipsychotic use during exacerbation (U=4.00, p=0.043) despite being negatively correlated to tic severity scores (ρ=−0.599, p=018), whereas increased IL-5 was associated with antibiotic use (U=6.5, p=0.035). During tic symptom remission, increased serum IL-4 levels were associated with antipsychotic (U=6.00, p=0.047) and antibiotic (U=1.00, p=0.016) use, whereas increased IL-12p70 (U=4.00, p=0.037) was associated with antibiotic use. Conclusions: These findings suggest a role for cytokine dysregulation in the pathogenesis of tic disorders. It also points toward the mechanistic involvement and potential diagnostic utility of cytokine monitoring, particularly TNF-α levels. Larger, systematic studies are necessary to further delineate the role of cytokines and medication influences on immunological profiling in tic disorders. PMID:25658821

  11. Cytokine correlations in youth with tic disorders.

    Science.gov (United States)

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

    2015-02-01

    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. Twenty-one patients, ages 4-17 years (average 10.63±2.34 years, 13 males), with a clinical diagnosis of Tourette's syndrome (TS) or chronic tic disorder (CTD), were selected based on having clinic visits that coincided with a tic symptom exacerbation and a remission. Ratings of tic severity were assessed using the Yale Global Tic Severity Scale (YGTSS) and serum cytokine levels (interleukin [IL]-2, IL-4, IL-5, IL-10, IL-12p70, IL-13, interferon [IFN]-γ, tumor necrosis factor [TNF]-α, and granulocyte macrophage-colony stimulating factor [GM-CSF]) were measured using Luminex xMAP technology. During tic symptom exacerbation, patients had higher median serum TNF-α levels (z=-1.962, p=0.05), particularly those on antipsychotics (U=9.00, p=0.033). Increased IL-13 was also associated with antipsychotic use during exacerbation (U=4.00, p=0.043) despite being negatively correlated to tic severity scores (ρ=-0.599, p=018), whereas increased IL-5 was associated with antibiotic use (U=6.5, p=0.035). During tic symptom remission, increased serum IL-4 levels were associated with antipsychotic (U=6.00, p=0.047) and antibiotic (U=1.00, p=0.016) use, whereas increased IL-12p70 (U=4.00, p=0.037) was associated with antibiotic use. These findings suggest a role for cytokine dysregulation in the pathogenesis of tic disorders. It also points toward the mechanistic involvement and potential diagnostic utility of cytokine monitoring, particularly TNF-α levels. Larger, systematic studies are necessary to further delineate the role of cytokines and medication influences on immunological profiling in tic disorders.

  12. Drug targets in the cytokine universe for autoimmune disease.

    Science.gov (United States)

    Liu, Xuebin; Fang, Lei; Guo, Taylor B; Mei, Hongkang; Zhang, Jingwu Z

    2013-03-01

    In autoimmune disease, a network of diverse cytokines is produced in association with disease susceptibility to constitute the 'cytokine milieu' that drives chronic inflammation. It remains elusive how cytokines interact in such a complex network to sustain inflammation in autoimmune disease. This has presented huge challenges for successful drug discovery because it has been difficult to predict how individual cytokine-targeted therapy would work. Here, we combine the principles of Chinese Taoism philosophy and modern bioinformatics tools to dissect multiple layers of arbitrary cytokine interactions into discernible interfaces and connectivity maps to predict movements in the cytokine network. The key principles presented here have important implications in our understanding of cytokine interactions and development of effective cytokine-targeted therapies for autoimmune disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Virulence and transmissibility of H1N2 influenza virus in ferrets imply the continuing threat of triple-reassortant swine viruses.

    Science.gov (United States)

    Pascua, Philippe Noriel Q; Song, Min-Suk; Lee, Jun Han; Baek, Yun Hee; Kwon, Hyeok-il; Park, Su-Jin; Choi, Eun Hye; Lim, Gyo-Jin; Lee, Ok-Jun; Kim, Si-Wook; Kim, Chul-Joong; Sung, Moon Hee; Kim, Myung Hee; Yoon, Sun-Woo; Govorkova, Elena A; Webby, Richard J; Webster, Robert G; Choi, Young-Ki

    2012-09-25

    Efficient worldwide swine surveillance for influenza A viruses is urgently needed; the emergence of a novel reassortant pandemic H1N1 (pH1N1) virus in 2009 demonstrated that swine can be the direct source of pandemic influenza and that the pandemic potential of viruses prevalent in swine populations must be monitored. We used the ferret model to assess the pathogenicity and transmissibility of predominant Korean triple-reassortant swine (TRSw) H1N2 and H3N2 influenza viruses genetically related to North American strains. Although most of the TRSw viruses were moderately pathogenic, one [A/Swine/Korea/1204/2009; Sw/1204 (H1N2)] was virulent in ferrets, causing death within 10 d of inoculation, and was efficiently transmitted to naive contact ferrets via respiratory droplets. Although molecular analysis did not reveal known virulence markers, the Sw/1204 virus acquired mutations in hemagglutinin (HA) (Asp-225-Gly) and neuraminidase (NA) (Ser-315-Asn) proteins during the single ferret passage. The contact-Sw/1204 virus became more virulent in mice, replicated efficiently in vitro, extensively infected human lung tissues ex vivo, and maintained its ability to replicate and transmit in swine. Reverse-genetics studies further indicated that the HA(225G) and NA(315N) substitutions contributed substantially in altering virulence and transmissibility. These findings support the continuing threat of some field TRSw viruses to human and animal health, reviving concerns on the capacity of pigs to create future pandemic viruses. Apart from warranting continued and enhanced global surveillance, this study also provides evidence on the emerging roles of HA(225G) and NA(315N) as potential virulence markers in mammals.

  14. Role of cytokines in Trypanosoma brucei-induced anaemia: A ...

    African Journals Online (AJOL)

    species Trypanosoma brucei that are transmitted by a tsetse fly (Glossina spp.) ... of autologous immunoglobulin antibodies on the red cell surfaces and also to ... development for the detection and management of anaemia in trypanosomiasis.

  15. 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.

  16. Cytokines and Pancreatic β-Cell Apoptosis

    DEFF Research Database (Denmark)

    Berchtold, L A; Prause, M; Størling, J

    2016-01-01

    The discovery 30 years ago that inflammatory cytokines cause a concentration, activity, and time-dependent bimodal response in pancreatic β-cell function and viability has been a game-changer in the fields of research directed at understanding inflammatory regulation of β-cell function and survival...... and the causes of β-cell failure and destruction in diabetes. Having until then been confined to the use of pathophysiologically irrelevant β-cell toxic chemicals as a model of β-cell death, researchers could now mimic endocrine and paracrine effects of the cytokine response in vitro by titrating concentrations...... of local, chronic islet inflammation. Since then, numerous studies have clarified how these bimodal responses depend on discrete signaling pathways. Most interest has been devoted to the proapoptotic response dependent upon mainly nuclear factor κ B and mitogen-activated protein kinase activation, leading...

  17. Progress of inflammatory cytokines in glaucoma

    Directory of Open Access Journals (Sweden)

    Ping Hu

    2015-12-01

    Full Text Available Glaucomais a group of diseases characterized by optic nerve damage and visual field defect, and pathological high intraocular pressure is a risk factor for glaucoma. Glaucoma is affected by the interaction of multiple genes and environmental factors, and inflammation may be involved in the pathogenesis of glaucoma. A great deal of studies have confirmed that high expression of connective tissue growth factor(CTGF, tumor necrosis factor-α(TNF-α, interleukins(ILs, nuclear factor-kappa B(NF-κBand various cytokines in the aqueous humor of patients with glaucoma, which have a close correlation with pathogenesis of glaucoma.This article reviews the progress of inflammatory cytokines and their relationship with glaucoma.

  18. Cytokines and the anorexia of infection: potential mechanisms and treatments.

    Science.gov (United States)

    McCarthy, D O

    2000-04-01

    Anorexia during infection is thought to be mediated by immunoregulatory cytokines such as interleukins 1 and 6 and tumor necrosis factor. This article reviews the potential mechanisms of action by which these cytokines are thought to suppress food intake during infection and examines the proposition that blocking of cytokine activity might be one approach to improving food intake of the infected host.

  19. Cytokine-producing T cell subsets in human leishmaniasis

    DEFF Research Database (Denmark)

    Kemp, Kåre

    2000-01-01

    Leishmania specific Th1/Th2 cells have been identified in humans as well as in mice. There is a correlation between the clinical outcome of the infection and the cytokine response profile. Generally, the production of Th2 cytokines leads to severe infection, whereas the production of Th1 cytokine...

  20. Screening the cytokines for diagnosis of tuberculous meningitis

    Institute of Scientific and Technical Information of China (English)

    王丽豪

    2014-01-01

    Objective To select cytokines for diagnosis of tuber-culous meningitis.Methods One hundred and twenty kinds of cytokines were detected with protein chips among two tuberculous meningitis cases,two viral meningitis cases and two noninfectious neurologic disease cases.The results were compared among different disease groups to select the differential cytokines,which were

  1. Cytokines in the physiopathology of depression

    OpenAIRE

    María Belén Paredes; María Eugenia Sulen

    2018-01-01

    This paper presents a bibliographical review on the relevance of the possible role of cytokines in depression. There is a consideration of the existing approaches to detection and diagnosis of depression; they are classified according to different criteria such as design methodologies and applications. Although the etiology of depression is still an issue, the focus of this paper is to highlight the various studies regarding the interactions of the immune system and brain activity linked to d...

  2. Association of Inflammatory Cytokines with Traditional and ...

    African Journals Online (AJOL)

    Annals of Medical and Health Sciences Research | Sep-Oct 2014 | Vol 4 ... and TNF‑α in study population were 11.7 (9.7) mg/l, 64.5 (75.2) pg/ml, and 25.3 ... cytokines also interact with various metabolic factors which are ..... European Prospective Investigation into Cancer and ... nutrition and role of one‑carbon metabolism.

  3. Cytokine Expression in Homozygous Sickle Cell Anaemia

    Directory of Open Access Journals (Sweden)

    Nnodim Johnkennedy

    2015-01-01

    Full Text Available Background: Sickle cell anaemia is an inherited disease in which the red blood cells become rigid and sticky, and change from being disc-shaped to being crescent-shaped. The change in shape is due to the presence of an abnormal form of haemoglobin. This results in severe pain and damage to some organs. Aim and Objective: The study was carried out to determine the levels of cytokine in sickle cell anemia. Material and Methods: Thirty confirmed sickle cell patients in steady state (HbSS-SS and thirty persons with normal haemoglobin (HbAA as well as sixteen sickle cell disease in crises (HbSS-cr between the ages of 15 to 30 years were selected in this study. Cytokines including interleukin 1 beta (IL- 1β, interleukin 2 (IL- 2, interleukin (IL-6, tumour necrosis factor alpha (TNF-α, and interferon gamma (IFN- λ were measured by commercially available ELISA kits. Results: The results obtained showed that the levels of TNF-α and IL-6 in sickle cell anaemia patients in crisis were significantly elevated when compared with sickle cell in steady state (P<0.05. Similarly, the levels of IL-1β, IL-6, and IFN- λ were significantly increased in sickle cell anaemia stable state when compared to HbAA subjects (P<0.05. Conclusion: This may probably implies that cytokine imbalance is implicated in the pathogenesis of sickle cell crisis. Also, cytokines could be used as an inflammatory marker as well as related marker in disease severity and hence therapeutic intervention.

  4. Immunoassay of serum polypeptide hormones by using 125I-labelled anti(-immunoglobulin G) antibodies.

    Science.gov (United States)

    Beck, P; Nicholas, H

    1975-03-01

    1. A technique for indirectly labelling antibodies to polypeptide hormones, by combining them with radioactively labelled anti-(immunoglobulin G) is described. (a) 125I-labelled anti-(rabbit immunoglobulin G) and anti-(guinea-pig immunoglobulin G) antibodies with high specific radioactivity were prepared after purification of the antibodies on immunoadsorbents containing the respective antigens. (b) Rabbit immunoglobulin G antibodies to human growth hormone, porcine glucagon and guinea-pig immunoglobulin G antibodies to bovine insulin and bovine parathyroid hormone were combined with immunoadsorbents containing the respective polypeptide hormone antigen. (c) The immunoglobulin G antibodies to the polypeptide hormones were reacted with 125-I-labelled anti-(immunoglobulin G) antibodies directed against the appropriate species of immunoglobulin G,and the anti-hormone antibodies were combined with the hormone-containing immunoadsorbent. (d) 125I-labelled anti-(immunoglobulin G) antibodies and anti-hormone antibodies were simultaneously eluted from the hormone-containing immunoadsorbent by dilute HCl, pH 2.0. After elution the anti-(immunoglobulin G) antibodies and antihormone antibodies were allowed to recombine at pH 8.0 and 4 degrees C. 2. The resultant immunoglobulin G-anti-immunoglobulin G complex was used in immunoradiometric (labelled antibody) and two-site assays of the respective polypeptide hormone. 3. By using these immunoassays, concentrations down to 90pg of human growth hormone/ml, 100 pg of bovine insulin/ml, 80 pg of bovine parathyroid hormone/ml and 150 pg of glucagon/ml were readily detected. Assays of human plasma for growth hormone and insulin by these methods showed good agreement with results obtained by using a directly 125I-labelled anti-hormone antibody in an immunoradiometric assay of human growth hormone or by radioimmunoassay of human insulin. 4. The method described allows immunoradiometric or two-site assays to be performed starting with as

  5. Subcutaneous immunoglobulin preserves muscle strength in chronic inflammatory demyelinating polyneuropathy

    DEFF Research Database (Denmark)

    Markvardsen, Lars Høj; Harbo, Thomas; Sindrup, Søren Hein

    2014-01-01

    evaluated after 3, 6 and 12 months. Primary end-points were changes in muscle strength evaluated by isokinetic dynamometry in four affected muscle groups and a composite score of muscle performance and function tests, including Medical Research Council (MRC) score, grip strength, 40-m walking test (40-MWT......BACKGROUND AND PURPOSE: Subcutaneous immunoglobulin (SCIG) is superior to placebo treatment for maintenance of muscle strength during 12 weeks in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). The present study evaluated whether SCIG preserves muscle strength for 1 year......) and nine-hole peg test (9-HPT). Secondary end-points were changes of each of the listed parameters at each time point as well as an overall disability sum score (ODSS). RESULTS: The dose of SCIG was significantly unaltered during the follow-up period. Overall the isokinetic dynamometry value increased by 7...

  6. Immunoglobulin subclass in experimental murine Toxocara cati infection

    Directory of Open Access Journals (Sweden)

    Kusnoto

    2017-11-01

    Full Text Available Aim: The aim of this study was to detect specific immunoglobulin (Ig that could be used to determine monoclonal antibody in conjugate-making an effort for the indirect enzyme-linked immunosorbent assay (ELISA diagnostic kit of toxocariasis in human. Materials and Methods: The study was conducted to assess the Ig profile, based on ELISA-isotyping, in mice infected with second stage larvae eggs of Toxocara cati. The optical density values of anti-T. cati mice serum IgG subclasses were analyzed by applying ANOVA factorial. Results: The specific IgG subclass in mice infected with T. cati mice was found to be IgG2β. Conclusion: Subclass of IgG, especially IgG2β, can provide leads about the use of the monoclonal antibody in conjugate making an effort for the indirect ELISA diagnostic kit.

  7. Antibody structural modeling with prediction of immunoglobulin structure (PIGS)

    DEFF Research Database (Denmark)

    Marcatili, Paolo; Olimpieri, Pier Paolo; Chailyan, Anna

    2014-01-01

    Antibodies (or immunoglobulins) are crucial for defending organisms from pathogens, but they are also key players in many medical, diagnostic and biotechnological applications. The ability to predict their structure and the specific residues involved in antigen recognition has several useful...... applications in all of these areas. Over the years, we have developed or collaborated in developing a strategy that enables researchers to predict the 3D structure of antibodies with a very satisfactory accuracy. The strategy is completely automated and extremely fast, requiring only a few minutes (∼10 min...... on average) to build a structural model of an antibody. It is based on the concept of canonical structures of antibody loops and on our understanding of the way light and heavy chains pack together....

  8. Intravenous Immunoglobulin in the Treatment of Primary Immunodeficiency Diseases.

    Science.gov (United States)

    De Ranieri, Deirdre; Fenny, Nana Sarkoah

    2017-01-01

    Intravenous immunoglobulin (IVIG) has been used as antibody replacement therapy in primary immunodeficiency diseases (PIDDs) for more than 50 years. Its role as a therapeutic agent has expanded over the past couple of decades as its anti-inflammatory and immune-modulatory mechanisms of action have been elucidated. It is now used "off-label" to treat other autoimmune diseases. This article focuses on the role of IVIG in the treatment of PIDDs characterized by absent or deficient antibody production. Replacement doses are given on a monthly basis in these conditions as a prophylactic measure to prevent acute and serious bacterial infections. [Pediatr Ann. 2017;46(1):e8-e12.]. Copyright 2017, SLACK Incorporated.

  9. Antibody structural modeling with prediction of immunoglobulin structure (PIGS)

    KAUST Repository

    Marcatili, Paolo

    2014-11-06

    © 2014 Nature America, Inc. All rights reserved. Antibodies (or immunoglobulins) are crucial for defending organisms from pathogens, but they are also key players in many medical, diagnostic and biotechnological applications. The ability to predict their structure and the specific residues involved in antigen recognition has several useful applications in all of these areas. Over the years, we have developed or collaborated in developing a strategy that enables researchers to predict the 3D structure of antibodies with a very satisfactory accuracy. The strategy is completely automated and extremely fast, requiring only a few minutes (~10 min on average) to build a structural model of an antibody. It is based on the concept of canonical structures of antibody loops and on our understanding of the way light and heavy chains pack together.

  10. Current clinical research of immunoglobulin G4-related orbital disease

    Directory of Open Access Journals (Sweden)

    Yang Wang

    2016-05-01

    Full Text Available Immunoglobulin G4-related disease(IgG4-related diseasehas received lots of attention in medical community as a recently recognized fibro-inflammatory condition. It is characterized by infiltration of IgG4-immunopositive plasmacytes and concentration of elevated serum IgG4. IgG4-related disease shows organ enlargement or nodular/hyperplastic lesions in various organs including the pancreas, hepatobiliary tract and orbit, which is called IgG4-related orbital disease. The diagnostic criteria for IgG4-related disease and IgG4-related orbital disease has recently been established, which is based on clinical, imaging and histopathologic features of the orbital lesions. Besides, attention should be drawn to the differentiation from other diseases. The treatment is empirical including corticosteroids, immunosuppressive drugs, radiotherapy, and rituximab. This article reviews clinical progression of IgG4-related orbital disease.

  11. Serum immunoglobulin levels in atomic bomb survivors, Hiroshima

    Energy Technology Data Exchange (ETDEWEB)

    Hall, C B; Hall, W J; Ashley, F W; Hamilton, H B

    1972-01-01

    Serum immunoglobulins (SI) were determined in 803 survivors and matched controls. Each subject's age, sex, health, exposure, and medical record were evaluated with respect to serum IgG, IgA, IgM levels. The IgG and IgA levels tended to be higher for this Hiroshima population than for Americans. Past exposure to ionizing radiation showed no significant correlation to SI levels. However, age and sex did influence the SI. IgM was significantly higher in females. With advancing age IgG and IgA increased in males, and IgM decreased in females. Elevated sedimentation rate and increased lymphocytes were accompanied by increased SI levels. Radiographic TB was detected in 45% of the population; IgG and IgA levels were somewhat elevated in these individuals. (DLC)

  12. Modes of Action of Intravenous Immunoglobulin in Bullous Pemphigoid.

    Science.gov (United States)

    Li, Ning; Culton, Donna; Diaz, Luis A; Liu, Zhi

    2018-06-01

    Bullous pemphigoid is an autoantibody-mediated skin blistering disease. Previous studies revealed that intravenous Ig is therapeutic in animal models of bullous pemphigoid by saturating the IgG-protective receptor FcRn, thereby accelerating degradation of pathogenic IgG. Sasaoka et al. demonstrate that the inhibitory effects of intravenous Ig on bullous pemphigoid are also associated with negative modulation of cytokine production by keratinocytes. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2010-01-01

    Background. Interleukin-4 (IL-4), a Th(2) 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' HLA-DRB1 typing by sequence specific oligonucleotide probe technique was compared to normal Egyptian population. We found significantly elevated serum IL-4 and total IgE in AA patients (particularly alopecia universalis, AU, and chronic patients) (P Serum IL-4 and IgE are elevated in nonatopic AA patients, particularly AU and chronic disease. Relevant susceptibility, chronicity, and severity HLADRB1 alleles may have a role in determining type, magnitude, and duration of immune response in AA favouring increased IL4 and IgE.

  14. Regulation and function of interleukin-36 cytokines.

    Science.gov (United States)

    Bassoy, Esen Yonca; Towne, Jennifer E; Gabay, Cem

    2018-01-01

    The interleukin (IL)-36 cytokines include 3 agonists, IL-36α, IL-36β, and IL-36γ that bind to a common receptor composed of IL-36R and IL-1RAcP to stimulate inflammatory responses. IL-36Ra is a natural antagonist that binds to IL-36R, but does not recruit the co-receptor IL-1RAcP and does not stimulate any intracellular responses. The IL-36 cytokines are expressed predominantly by epithelial cells and act on a number of cells including immune cells, epithelial cells, and fibroblasts. Processing of the N-terminus is required for full agonist or antagonist activity for all IL-36 members. The role of IL-36 has been extensively demonstrated in the skin where it can act on keratinocytes and immune cells to induce a robust inflammatory response that has been implicated in psoriatic disorders. Emerging data also suggest a role for this cytokine family in pulmonary and intestinal physiology and pathology. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Cytokine Tuning of Intestinal Epithelial Function

    Directory of Open Access Journals (Sweden)

    Caroline Andrews

    2018-06-01

    Full Text Available The intestine serves as both our largest single barrier to the external environment and the host of more immune cells than any other location in our bodies. Separating these potential combatants is a single layer of dynamic epithelium composed of heterogeneous epithelial subtypes, each uniquely adapted to carry out a subset of the intestine’s diverse functions. In addition to its obvious role in digestion, the intestinal epithelium is responsible for a wide array of critical tasks, including maintaining barrier integrity, preventing invasion by microbial commensals and pathogens, and modulating the intestinal immune system. Communication between these epithelial cells and resident immune cells is crucial for maintaining homeostasis and coordinating appropriate responses to disease and can occur through cell-to-cell contact or by the release or recognition of soluble mediators. The objective of this review is to highlight recent literature illuminating how cytokines and chemokines, both those made by and acting on the intestinal epithelium, orchestrate many of the diverse functions of the intestinal epithelium and its interactions with immune cells in health and disease. Areas of focus include cytokine control of intestinal epithelial proliferation, cell death, and barrier permeability. In addition, the modulation of epithelial-derived cytokines and chemokines by factors such as interactions with stromal and immune cells, pathogen and commensal exposure, and diet will be discussed.

  16. Cytokines in systemic lupus erythematosus: far beyond Th1/Th2 dualism lupus: cytokine profiles.

    Science.gov (United States)

    Guimarães, Poliana Macedo; Scavuzzi, Bruna Miglioranza; Stadtlober, Nicole Perugini; Franchi Santos, Lorena Flor da Rosa; Lozovoy, Marcell Alysson Batisti; Iriyoda, Tatiana Mayumi Veiga; Costa, Neide Tomimura; Reiche, Edna Maria Vissoci; Maes, Michael; Dichi, Isaias; Simão, Andréa Name Colado

    2017-10-01

    The aims of this study were to delineate cytokine profiles of systemic lupus erythematosus (SLE), construct prediction models for diagnosis and disease activity using those profiles, and to examine the associations between TNFB Ncol polymorphism, body mass index (BMI) and vitamin D levels with cytokine levels. Two hundred SLE patients and 196 healthy controls participated in this case-control study. Plasma cytokines levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1β, IL- 4, IL-6, IL-10, IL-12 and IL-17 were measured and cytokines profiles were computed. IL-6, IL-12, IL-17, IFN-γ and IL-10 levels were significantly higher in SLE, while IL-4 was lower in SLE. The Th1/Th2 and Th1+Th17/Th2 profiles were significantly higher in SLE than in healthy controls, whereas there were no significant differences in the proinflammatory cytokine profile (TNFα+IL-6+IL-1β). In total, 90.4% of all subjects were correctly classified using Th1+Th17 profile and IL-10 (positively associated) and IL-4 (negatively associated) as predictor variables (sensitivity=66.7% and specificity=96.9%). In all, 20.9% of the variance in the SLE Disease Activity Index was predicted by the Th1+Th17/Th2 ratio, IL-10 and BMI (all positively) and proinflammatory profile (inversely associated). B1/B1 genotype is accompanied by increased IL-17 and Th17/Th2 ratio, while B1/B2 genotype is accompanied by higher IL-4 and IFNγ values. 25-OH vitamin D was inversely associated with IFN-γ levels. SLE is accompanied by Th1, Th17 and Treg profile and lowered IL-4 production. Lowered vitamin D levels and B1/B1 genotype, but not BMI, contribute to changes in cytokines profiles. Future treatments should target Th1, Th2 and Th17 profiles rather than inflammatory cytokines.

  17. Intravenous immunoglobulin in ABO and Rh hemolytic diseases of newborn.

    Science.gov (United States)

    Nasseri, Fatemeh; Mamouri, Gholam A; Babaei, Homa

    2006-12-01

    To evaluate whether the use of intravenous immunoglobulin in newborn infants with isoimmune hemolytic jaundice due to Rh and ABO incompatibility is an effective treatment in reducing the need for exchange transfusion. This study included all direct Coombs' test positive Rh and ABO isoimmunized babies, who admitted in the Neonatal Intensive Care Unit of Ghaem Hospital of Mashhad University of Medical Sciences, Iran, from October 2003 to October 2004. Significant hyperbilirubinemia was defined as rising by >or=0.5 mg/dl per hour. Babies were randomly assigned to received phototherapy with intravenous immunoglobulin (IVIg) 0.5 g/kg over 4 hours, every 12 hours for 3 doses (study group) or phototherapy alone (control group). Exchange transfusion was performed in any group if serum bilirubin exceeded >or=20mg/dl or rose by >or=1mg/dl/h. A total of 34 babies were eligible for this study (17 babies in each group). The number of exchange transfusion, duration of phototherapy and hospitalization days, were significant shorter in the study group versus control group. When we analyzed the outcome results in ABO and Rh hemolytic disease separately, the efficacy of IVIg was significantly better in Rh versus ABO isoimmunization. Late anemia was more common in the IVIg group 11.8% versus 0%, p=0.48. Adverse effects were not observed during IVIg administration. Administration of IVIg to newborns with significant hyperbilirubinemia due to Rh hemolytic disease reduced the need for exchange transfusion but in ABO hemolytic disease there was no significant difference between IVIg and double surface blue light phototherapy.

  18. Secretory immunoglobulin purification from whey by chromatographic techniques.

    Science.gov (United States)

    Matlschweiger, Alexander; Engelmaier, Hannah; Himmler, Gottfried; Hahn, Rainer

    2017-08-15

    Secretory immunoglobulins (SIg) are a major fraction of the mucosal immune system and represent potential drug candidates. So far, platform technologies for their purification do not exist. SIg from animal whey was used as a model to develop a simple, efficient and potentially generic chromatographic purification process. Several chromatographic stationary phases were tested. A combination of two anion-exchange steps resulted in the highest purity. The key step was the use of a small-porous anion exchanger operated in flow-through mode. Diffusion of SIg into the resin particles was significantly hindered, while the main impurities, IgG and serum albumin, were bound. In this step, initial purity was increased from 66% to 89% with a step yield of 88%. In a second anion-exchange step using giga-porous material, SIg was captured and purified by step or linear gradient elution to obtain fractions with purities >95%. For the step gradient elution step yield of highly pure SIg was 54%. Elution of SIgA and SIgM with a linear gradient resulted in a step yield of 56% and 35%, respectively. Overall yields for both anion exchange steps were 43% for the combination of flow-through and step elution mode. Combination of flow-through and linear gradient elution mode resulted in a yield of 44% for SIgA and 39% for SIgM. The proposed process allows the purification of biologically active SIg from animal whey in preparative scale. For future applications, the process can easily be adopted for purification of recombinant secretory immunoglobulin species. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. [Correlation of serum IL-16, IL-18 levels and immunoglobulins in children with asthma].

    Science.gov (United States)

    Xue, Yi-Nan; Zou, Xian-De; Wu, Jia-Ling

    2006-02-01

    This study examined the changes of serum levels of interleukin (IL)-16, IL-18 and immunoglobulins and the correlation of serum IL-16, IL-18 levels and immunoglobulins in children with asthma and aimed to explore the role of IL-16, IL-18 and immunoglobulins in the pathogenesis of asthma. Thirty-four children with asthma and 21 age and gender-matched healthy children were enrolled in this study. The levels of IL-16, IL-18 and immunoglobulin E (IgE) were determined using ELISA. Immunoglobulin G (IgG), immunoglobulin M (IgM) and immunoglobulin A (IgA) were detected by immunoturbidimetry. The levels of IL-16, IL-18 and IgE in patients with asthma at both acute attack and convalescence stages were significantly higher than those in healthy controls. An increased IgG and a decreased IgA levels were found in asthmatic patients at the acute attack stage. There was a positive correlation between the IL-16 and IL-18 levels at both acute attack and convalescence stages of asthma (r=0.70, P attack stage of asthma (r=0.624, P asthma. The immunologic imbalance exists in children with asthma at both acute attack and convalescence stages. Anti-allergic therapy should be administered through the acute attack to the convalescence stages of asthma.

  20. Fragments of the constant region of immunoglobulin light chains are constituents of AL-amyloid proteins

    DEFF Research Database (Denmark)

    Olsen, K E; Sletten, K; Westermark, Per

    1998-01-01

    Immunoglobulin light chains are the precursor proteins of AL-amyloidosis. In the fibril formation process properties of the variable part of the immunoglobulin light chains are believed to be of major importance. In this work it is shown that fragments of the constant part of the immunoglobulin l...... light chain are a constituent of the AL-amyloid proteins of kappa type. A specific antiserum has identified these fragments in gel filtration fractions where the absorbance approached the base line after the main retarded peak. The fragments are small and have been overlooked previously......Immunoglobulin light chains are the precursor proteins of AL-amyloidosis. In the fibril formation process properties of the variable part of the immunoglobulin light chains are believed to be of major importance. In this work it is shown that fragments of the constant part of the immunoglobulin...... in the purification process. The significance of the constant part in AL-proteins is unclear, but adds new aspects to the discussion of pre- or post-fibrillogenic cleavage of the immunoglobulin light chains....

  1. LYMPHOCYTE SUBSETS AND CYTOKINES IN BLOOD AND CEREBROSPINAL FLUID IN CHILDREN WITH VIRAL AND BACTERIAL MENINGITIS

    Directory of Open Access Journals (Sweden)

    L. A. Alekseeva

    2016-01-01

    an expressed system response of IL-8 and IL-10. Liquor T-lymphocyte content was relatively correlated with blood indicators whereas the fraction of NK exceeded it, and B-lymphocyte content was 3–4 times higher than in patients with viral meningitis. There was IL-6, IL-10, IFNγ and IL-4 response intrathecally, and 10-multiply-growth of IgG level. Thus, the redistribution of lymphocyte subpopulations, and system and local cytokine response in children with meningitis have both common and special features depending on the aetiology and severity of disease. Phenotyping of lymphocytes and determination of both cytokines and immunoglobulins simultaneously in two biologic fluid allow to clear up the pathogenetic value of immunologic abnormalities in blood and cerebrospinal fluid of the patients in the aspect of interactions between cell and humoral factors of system and local immune response in neuroinfections of various aetiology.

  2. 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

  3. 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

  4. Cytokines, cytokine antagonists, and soluble adhesion molecules in pediatric OMS and other neuroinflammatory disorders.

    Science.gov (United States)

    Pranzatelli, Michael R; Tate, Elizabeth D; McGee, Nathan R; Colliver, Jerry A

    2013-03-15

    To test for hypothesized disease- and treatment-induced changes in cytokines and adhesion molecules in children with opsoclonus-myoclonus syndrome (OMS). Multiplex bead assay technology was used for simultaneous measurement of 34 soluble cytokines in cerebrospinal fluid (CSF) and serum. Soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) were measured by ELISA. In total, there were 388 children (239 OMS, 114 controls, and 35 other inflammatory neurological disorders (OIND)). In untreated OMS, mean CSF IL-6 was elevated 2.3-fold, but 67-fold in OIND, without significant differences in other CSF cytokines. Mean serum concentrations of sIL-2Ra (+50%) and CXCL1 (+70%) (pOMS than controls (p=0.005), as was serum CCL11 and IL-13 in treated OMS. Mean CSF CCL4 and IL-1Ra were selectively higher in IVIg-treated OMS (p≤0.0001). CSF sICAM-1 was elevated only in OIND (3.3-fold); serum sICAM-1 was higher in untreated OMS (+21%); and sVCAM-1 was not affected. No correlations with OMS severity or duration were identified. Novel cytokine, cytokine antagonist, and soluble adhesion molecule abnormalities due to OMS or treatment were found. However, the normality of much of the data strengthens previous findings implicating B cell mechanisms. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Regulation of cytokines by small RNAs during skin inflammation

    Directory of Open Access Journals (Sweden)

    Mikkelsen Jacob G

    2010-07-01

    Full Text Available Abstract Intercellular signaling by cytokines is a vital feature of the innate immune system. In skin, an inflammatory response is mediated by cytokines and an entwined network of cellular communication between T-cells and epidermal keratinocytes. Dysregulated cytokine production, orchestrated by activated T-cells homing to the skin, is believed to be the main cause of psoriasis, a common inflammatory skin disorder. Cytokines are heavily regulated at the transcriptional level, but emerging evidence suggests that regulatory mechanisms that operate after transcription play a key role in balancing the production of cytokines. Herein, we review the nature of cytokine signaling in psoriasis with particular emphasis on regulation by mRNA destabilizing elements and the potential targeting of cytokine-encoding mRNAs by miRNAs. The proposed linkage between mRNA decay mediated by AU-rich elements and miRNA association is described and discussed as a possible general feature of cytokine regulation in skin. Moreover, we describe the latest attempts to therapeutically target cytokines at the RNA level in psoriasis by exploiting the cellular RNA interference machinery. The applicability of cytokine-encoding mRNAs as future clinical drug targets is evaluated, and advances and obstacles related to topical administration of RNA-based drugs targeting the cytokine circuit in psoriasis are described.

  6. Inhibition of neutrophil migration by aggregated immunoglobulin attached to micropore membranes.

    Science.gov (United States)

    Kemp, A S; Brown, S

    1980-01-01

    The effect of substrate-bound immunoglobulin on neutrophil migration was examined. Immunoglobulin aggregates bound to micropore membranes inhibited the neutrophil response to a chemotactic stimulus. This inhibition was reversed by the presence of aggregates in suspension suggesting competition between substrate-bound and free aggregates for neutrophil surface binding sites. The immobilization of neutrophils by substrate-bound aggregated immunoglobulin suggests a mechanism for the accumulation of neutrophils at sites of immune complex deposition and tissue-bound antibodies in vivo. PMID:7380477

  7. Swine plasma immunoglobulins for prevention and treatment of post-weaning diarrhoea: Safety and Preliminary results

    DEFF Research Database (Denmark)

    Hedegaard, Chris Juul; Strube, Mikael Lenz; Bendix Hansen, Marie

    . coli F4+ induced PWD, we observed that piglets given IgG as a feed supplement cleared the E coli infection significantly faster than control weaner piglets not receiving an immunoglobulin feed supplement. Furthermore, deep sequencing of the ileal microbiota showed a significantly lowered colonization...... their adhesion to porcine epithelial cells in vitro. As the immunoglobulin fraction is intended for oral use as a feed supplement, we also tested the safety of feeding 4 grams of natural immunoglobulins to 4-5 week old weaner piglets for 14 days and observed no adverse effects. In an experimental model of E...

  8. [Sequencing and analysis of complete genome of rabies viruses isolated from Chinese Ferret-Badger and dog in Zhejiang province].

    Science.gov (United States)

    Lei, Yong-Liang; Wang, Xiao-Guang; Tao, Xiao-Yan; Li, Hao; Meng, Sheng-Li; Chen, Xiu-Ying; Liu, Fu-Ming; Ye, Bi-Feng; Tang, Qing

    2010-01-01

    Based on sequencing the full-length genomes of four Chinese Ferret-Badger and dog, we analyze the properties of rabies viruses genetic variation in molecular level, get the information about rabies viruses prevalence and variation in Zhejiang, and enrich the genome database of rabies viruses street strains isolated from China. Rabies viruses in suckling mice were isolated, overlapped fragments were amplified by RT-PCR and full-length genomes were assembled to analyze the nucleotide and deduced protein similarities and phylogenetic analyses from Chinese Ferret-Badger, dog, sika deer, vole, used vaccine strain were determined. The four full-length genomes were sequenced completely and had the same genetic structure with the length of 11, 923 nts or 11, 925 nts including 58 nts-Leader, 1353 nts-NP, 894 nts-PP, 609 nts-MP, 1575 nts-GP, 6386 nts-LP, and 2, 5, 5 nts- intergenic regions(IGRs), 423 nts-Pseudogene-like sequence (psi), 70 nts-Trailer. The four full-length genomes were in accordance with the properties of Rhabdoviridae Lyssa virus by BLAST and multi-sequence alignment. The nucleotide and amino acid sequences among Chinese strains had the highest similarity, especially among animals of the same species. Of the four full-length genomes, the similarity in amino acid level was dramatically higher than that in nucleotide level, so the nucleotide mutations happened in these four genomes were most synonymous mutations. Compared with the reference rabies viruses, the lengths of the five protein coding regions had no change, no recombination, only with a few point mutations. It was evident that the five proteins appeared to be stable. The variation sites and types of the four genomes were similar to the reference vaccine or street strains. And the four strains were genotype 1 according to the multi-sequence and phylogenetic analyses, which possessed the distinct district characteristics of China. Therefore, these four rabies viruses are likely to be street viruses

  9. Esculetin from Fraxinus rhynchophylla attenuates atopic skin inflammation by inhibiting the expression of inflammatory cytokines.

    Science.gov (United States)

    Jeong, Na-Hee; Yang, Eun-Ju; Jin, Meiling; Lee, Jong Yeong; Choi, Young-Ae; Park, Pil-Hoon; Lee, Sang-Rae; Kim, Sun-Uk; Shin, Tae-Yong; Kwon, Taeg Kyu; Jang, Yong Hyun; Song, Kyung-Sik; Kim, Sang-Hyun

    2018-06-01

    Atopic dermatitis (AD) is a common chronic inflammatory skin disorder afflicting from infancy to adults with itching, scratching, and lichenification. We aimed to investigate the effects of esculetin from Fraxinus rhynchophylla on atopic skin inflammation. For induction of atopic skin inflammation, we exposed the ears of female BALB/c mice to house dust mite (Dermatophagoides farinae extract, DFE) and 2,4-dinitrochlorobenzene (DNCB) for 4 weeks. Oral administration of esculetin reduced the symptoms of DFE/DNCB-induced atopic skin inflammation, which were evaluated based on ear swelling and number of scratch bouts. The immunoglobulin (Ig) E, IgG2a, and histamine levels in serum were decreased and inflammatory cell infiltration in skin tissue was reduced by the esculetin. It suppressed production of Th1, Th2 and Th17-related cytokines such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-4, IL-13, IL-31 and IL-17 in the ear tissue. Furthermore, we investigated the effects of esculetin on activated keratinocytes, which are representative cells used for studying the pathogenesis of acute and chronic atopic skin inflammation. As results, esculetin suppressed gene expression of Th1, Th2 and Th17 cytokines and the activation of nuclear factor-κB and signal transducer and activator of transcription 1 in TNF-α/IFN-γ-stimulated keratinocytes. Taken together, these results imply that esculetin attenuated atopic skin inflammation, suggesting that esculetin could be a potential therapeutic candidate for the treatment of AD. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Cytokine profile and pathology in human leishmaniasis

    Directory of Open Access Journals (Sweden)

    Ribeiro-de-Jesus A.

    1998-01-01

    Full Text Available The clinical spectrum of leishmaniasis and control of the infection are influenced by the parasite-host relationship. The role of cellular immune responses of the Th1 type in the protection against disease in experimental and human leishmaniasis is well established. In humans, production of IFN-g is associated with the control of infection in children infected by Leishmania chagasi. In visceral leishmaniasis, an impairment in IFN-g production and high IL-4 and IL-10 levels (Th2 cytokines are observed in antigen-stimulated peripheral blood mononuclear cells (PBMC. Moreover, IL-12 restores IFN-g production and enhances the cytotoxic response. IL-10 is the cytokine involved in down-regulation of IFN-g production, since anti-IL-10 monoclonal antibody (mAb restores in vitro IFN-g production and lymphoproliferative responses, and IL-10 abrogates the effect of IL-12. In cutaneous and mucosal leishmaniasis, high levels of IFN-g are found in L. amazonensis-stimulated PBMC. However, low or absent IFN-g levels were observed in antigen-stimulated PBMC from 50% of subjects with less than 60 days of disease (24 ± 26 pg/ml. This response was restored by IL-12 (308 ± 342 pg/ml and anti-IL-10 mAb (380 ± 245 pg/ml (P<0.05. Later during the disease, high levels of IFN-g and TNF-a are produced both in cutaneous and mucosal leishmaniasis. After treatment there is a decrease in TNF-a levels (366 ± 224 pg/ml before treatment vs 142 ± 107 pg/ml after treatment, P = 0.02. Although production of IFN-g and TNF-a might be involved in the control of parasite multiplication in the early phases of Leishmania infection, these cytokines might also be involved in the tissue damage seen in tegumentary leishmaniasis

  11. Cytokines in the modulation of eosinophilia

    Directory of Open Access Journals (Sweden)

    Faccioli Lúcia H

    1997-01-01

    Full Text Available In this review we discuss our recently results showing interleukin 5 (IL-5 involvement in eosinophil migration and in the maintenance of eosinophilia in blood, bone marrow, lung and peritoneal cavity, in a visceral larva migrans syndrome model using guinea-pigs infected with Toxocara canis. We also describe the sequential release of TNF-alpha and IL-8 during the course of infection, and the interaction between these cytokines and IL-5 during infection. Finally we propose a new biological role for IL-5, at least in our model, as a modulator of IL-8 release and secretion.

  12. [Membrane-bound cytokine and feedforward regulation].

    Science.gov (United States)

    Wu, Ke-Fu; Zheng, Guo-Guang; Ma, Xiao-Tong; Song, Yu-Hua

    2013-10-01

    Feedback and feedforward widely exist in life system, both of them are the basic processes of control system. While the concept of feedback has been widely used in life science, feedforward regulation was systematically studied in neurophysiology, awaiting further evidence and mechanism in molecular biology and cell biology. The authors put forward a hypothesis about the feedforward regulation of membrane bound macrophage colony stimulation factor (mM-CSF) on the basis of their previous work. This hypothesis might provide a new direction for the study on the biological effects of mM-CSF on leukemia and solid tumors, and contribute to the study on other membrane bound cytokines.

  13. Original paper Cytokine profiles in axial spondyloarthritis

    Directory of Open Access Journals (Sweden)

    Marta Madej

    2015-04-01

    Full Text Available Objectives: Current studies concentrate on the cytokine network and its role in the pathogenesis of spondyloarthritis (SpA. In this study, we analyzed whether the serum cytokine profile (interleukins: IL-10, IL-11, IL-12, IL-15, IL-17, IL-23 and IL-33 correlates with demographic data, clinical manifestations, disease activity and treatment outcome in a group of patients with axial spondyloarthritis. Material and methods: Forty-nine patients with an established diagnosis of axial spondyloarthritis (aSpA and 19 healthy volunteers as controls were enrolled in the study. Clinical evaluation included patient’s medical history, 44 joint count, back pain intensity and global disease activity in the preceding week (VAS, the duration of morning stiffness and blood tests. Disease activity was assessed using BASDAI and ASDAS-CRP. Serum concentration of IL-10, IL-11, IL-12, IL-15, IL-17, IL-23 and IL-33 was determined. Results : In patients with aSpA, elevated serum concentration of IL-10, IL-15, IL-17 and IL-23 was detected. In the aSpA group we detected higher values of serum concentration of IL-23 and IL-33 in the subgroup with anterior uveitis (83.1 ±184.0 pg/ml vs. 14.0 ±17.1 pg/ml, p < 0.0001 and 45.5 ±71.9 pg/ml vs. 18.4 ±14.3 pg/ml, p < 0.0001, respectively. Additionally, in the subgroup with peripheral arthritis, elevation of serum concentration of IL-12 (249.3 ±246.9 pg/ml vs. 99.9 ±105.9 pg/ml, p = 0.0001 was detected. Patients with preradiological SpA had higher serum concentration of IL-17 than patients with established diagnosis of AS (6.37 ±8.50 pg/ml vs. 2.04 ±2.98 pg/ml, p = 0.0295. No differences in serum concentration of analyzed cytokines were found between the subgroup with low to moderate disease activity and the subgroup with high to very high disease activity. Conclusions : We report that in aSpA patients, compared to controls, elevated serum concentrations of IL-10, IL-15, IL-17 and IL-23 were observed. Some cytokines may

  14. Hypothyroidism and depression: Are cytokines the link?

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    Parimal S Tayde

    2017-01-01

    Full Text Available Context: Primary hypothyroidism has been thought of as an inflammatory condition characterized by raised levels of cytokines such as C-reactive protein (CRP, interleukin-6 (IL-6, and tumor necrosis factor-alpha (TNF-α. Depression is also well known to occur in hypothyroidism. Depression is also characterized by elevated inflammatory cytokines. We planned to study whether cytokines play an important part in linking these two conditions. Objectives: (1 To know the prevalence of depression in overt hypothyroidism due to autoimmune thyroid disease. (2 To correlate the levels of inflammatory markers with the occurrence of depression. (3 To study the effect of levothyroxine on inflammatory markers and depression. Materials and Methods: In this longitudinal, case–controlled study, 33 patients with autoimmune hypothyroidism (thyroid-stimulating hormone >10 uIU/ml were included with 33 age-, sex-, and body max index-matched healthy controls. Individuals were tested for Serum TNF-α, IL-6, high-sensitivity-CRP (hs-CRP. They were assessed for depression using Montgomery Asberg Depression Rating Scale (MADRS and World Health Organization Quality of Life (QOL Scale. Patients received L Thyroxine titrated to achieve euthyroidism and were reassessed for inflammatory markers and cognitive dysfunction. Results: Nineteen patients (57% had mild to moderate depression (MADRS >11. After 6 months of treatment, eight patients (42% had remission of depression with significant improvement in QOL scores (P < 0.05. TNF-α, IL-6, and hs-CRP were significantly elevated in patients compared with controls and reduced with therapy but did not reach baseline as controls. The change in inflammatory markers correlated with improvement in QOL scores in social and environmental domains (P < 0.01. Conclusions: Primary autoimmune hypothyroidism is an inflammatory state characterized by elevated cytokines which decline with LT4 therapy. It is associated with depression and poor

  15. From cytokines to pragmatic designs: changing paradigms.

    Science.gov (United States)

    Heddle, Nancy M

    2017-10-01

    Emily Cooley was a well-respected medical technologist and morphologist with a remarkable skill set. She was highly regarded both professionally and personally. The "Emily Cooley Lectureship and Award" was established to honor her in particular and medical technologists in general. This article first reviews how a medical laboratory technologist was inspired to become a clinical researcher, then goes on to describe research that led to the discovery of cytokines as the cause of febrile nonhemolytic transfusion and the use of a pragmatic randomized controlled trial design to address evidence of harm when stored red blood cells were transfused. Important lessons for performing quality, meaningful research are highlighted. © 2017 AABB.

  16. Salivary immunoglobulin classes in Nigerian smokers with periodontitis.

    Science.gov (United States)

    Olayanju, Olatunde A; Rahamon, Sheu K; Joseph, Ijeboime O; Arinola, Olatunbosun G

    2012-10-26

    To determine the levels of salivary immunoglobulin classes in Nigerian smokers and non-smokers with periodontitis. Sixty-nine individuals were recruited into this study after obtaining informed consent. They were subdivided into three groups that consisted of 20 (aged 46 ± 11 years) cigarette smokers with periodontitis (S+P); 24 (40 ± 12 years) smokers without periodontitis (S-P); and 25 (53 ± 11 years) non-smokers with periodontitis (NS+P). An oral and maxillofacial surgeon used radiographs for periodontal probing for the diagnosis of periodontitis. The smokers included subjects who smoked at least six cigarettes per day and all the periodontitis patients were newly diagnosed. About 5 mL of unstimulated saliva was expectorated by each subject into plain sample bottles. Salivary immunoglobulin levels were estimated using enzyme linked immunosorbent assay. Student's t test was used to determine significant differences between the means. Values of P vs 670.0 ± 110 ng/mL, P = 0.000) and IgM (644.5 ± 160.0 ng/mL vs 791.4 ± 43.7 ng/mL, P = 0.000) were significantly lower in the S+P compared with NS+P group. Salivary IgA (570.4 ± 145.6 ng/mL vs 670.0 ± 110 ng/mL, P = 0.008) and IgM (703.1 ± 169.3 ng/mL vs 791.4 ± 43.7 ng/mL, P = 0.012) levels were significantly lower in the S-P compared with NS+P group. Only one (5%) periodontal patient had detectable levels of salivary IgE (0.20 IU/mL). Similarly, only one smoker (4.17%) had detectable levels of salivary IgE (0.04 IU/mL) and two non-smokers (9.52%) had detectable levels of IgE (0.24 IU/mL). Our study suggests that reduced salivary IgA and IgM levels in smokers with periodontitis could enhance increased susceptibility to periodontitis.

  17. Hyper-immunoglobulin D syndrome with novel mutations in an afebrile infant.

    Science.gov (United States)

    Cadmus, Simi D; Green, Reid; Carrasco, Ruy; Levy, Moise L; Diaz, Lucia Z

    2018-03-30

    Hyper-immunoglobulin D syndrome is a rare autosomal-recessive autoinflammatory syndrome in which a mevalonate kinase deficiency results due to mutations of the mevalonate kinase gene. We report a case of an Asian male infant who was found to have hyper-immunoglobulin D syndrome in the absence of fever. His skin manifestations included cephalic pustulosis as well recurrent transient and fixed pink plaques and nodules on the face and extremities. Subsequent examination revealed hyper-immunoglobulin D syndrome with two novel allelic mutations in the mevalonate kinase gene: c.895G > A (p.D299N) and c.1168C > T (p.Q390). It is important for dermatologists to recognize the varied cutaneous presentations of hyper-immunoglobulin D syndrome because rapid diagnosis and treatment can significantly affect outcomes. © 2018 Wiley Periodicals, Inc.

  18. Diversity analysis of the immunoglobulin M heavy chain gene in Nile ...

    African Journals Online (AJOL)

    nu tom

    2015-07-22

    Jul 22, 2015 ... related industries and supply chains, such as hatcheries, feed manufacturers ... system has a high risk of disease outbreaks. The bulk of ...... immunoglobulin heavy-chain locus in zebrafish: identification and expression of a ...

  19. Intravenous immunoglobulin response in treatment-naïve chronic inflammatory demyelinating polyradiculoneuropathy

    NARCIS (Netherlands)

    Kuitwaard, Krista; Hahn, Angelika F.; Vermeulen, Marinus; Venance, Shannon L.; van Doorn, Pieter A.

    2015-01-01

    There is no consensus on which treatment should be used preferentially in individual patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Patients unlikely to respond to intravenous immunoglobulin (IVIg) could be prescribed corticosteroids first to avoid high cost and a delayed

  20. Solid-phase radioimmunoassay of immunoglobulins G, A and M: applicability in analysis of sucrose gradients

    Energy Technology Data Exchange (ETDEWEB)

    Eriksen, E F; Danielsen, H [Aarhus Kommunehospital (Denmark). Medical Department C; Johansen, A S [Aarhus Univ. (Denmark). Institute of Medical Biochemistry; Larsson, L I [Unit of Histochemistry, University Institute of Pathology, Copenhagen, Denmark

    1984-01-01

    A simple and sensitive solid-phase radioimmunoassay for the detection of immunoglobulins G, A and M in sucrose gradients is described. The solid-phase consisted of immunoglobulins adsorbed to polystyrene tubes. Using buffers without detergent and /sup 125/I-labeled sheep anti-rabbit IgA as radioligand, the assay was able to detect 0.8 ng per tube in the IgG assay and 1.6 ng per tube in the IgA and IgM assays. Standard curves with antigen dissolved in 10% and 32% sucrose were superimposable and did not deviate from standard curves with antigen dissolved in buffer without sucrose. Using these techniques on ultracentrifugation samples from patients with systemic lupus erythematosus, Schoenlein-Henoch nephritis and IgA glorulonephritis is was possible to detect both immunoglobulin fragments and immunoglobulin aggregates at the same time without prior dialysis of the samples.

  1. Immunoglobulins of patients with Cushing's syndrome due to pigmented adrenocortical micronodular dysplasia stimulate in vitro steroidogenesis

    NARCIS (Netherlands)

    Wulffraat, N. M.; Drexhage, H. A.; Wiersinga, W. M.; van der Gaag, R. D.; Jeucken, P.; Mol, J. A.

    1988-01-01

    The putative stimulation of adrenal steroid production by immunoglobulins (Igs) of five patients with pigmented adrenocortical micronodular dysplasia and clinical Cushing's syndrome was investigated. Ascorbate depletion, a process linked to steroid production, was measured by a cyto-chemical

  2. Salivary immunoglobulin classes in Nigerian cigarette smokers: Indication for increased risk of oral diseases

    Directory of Open Access Journals (Sweden)

    Ayodeji Olatunde Olayanju

    2012-01-01

    Conclusion: Our study showed that there is decreased salivary IgM in smokers. This observation suggests that reduced salivary immunoglobulin level of IgM might be involved in the pathogenesis of oral diseases in cigarette smokers.

  3. PARTIAL PURIFICATION AND IMMUNE-BIOCHEMICAL CHARACTERIZATION OF DOG SERUM IMMUNOGLOBULIN G

    Directory of Open Access Journals (Sweden)

    Manoj Kumar

    2013-06-01

    Full Text Available In the present study Immunoglobulin G was purified from serum of dog by gel filtration chromatography on Sephacryl S-200. SDS- PAGE analysis of purified dog IgG showed major polypeptides of 66 kDa, 52.40 kDa and 20.72 kDa. The purified Immunoglobulin has been found to be immune-reactive by DID test and Western Blot analysis when treated against hyperimmune sera which was raised in rabbit.

  4. Evaluation of salivary immunoglobulin A levels in tobacco smokers and patients with recurrent aphthous ulcers

    OpenAIRE

    Shilpashree, H. S.; Sarapur, Shriprasad

    2012-01-01

    Objectives: The aim of the present study was to analyze the influence of smoking on the salivary immunoglobulin response in smokers and to evaluate the salivary immunoglobulin A in patients with recurrent aphthous ulcers. Materials and Methods: The study included total of 80 subjects, of whom 40 were having history of chronic smoking habit, 20 were clinically diagnosed cases of recurrent aphthous ulcer and 20 were in the control group. Sample of unstimulated saliva was collected, centrifuged ...

  5. Relationship of cytokines and cytokine signaling to immunodeficiency disorders in the mouse

    Directory of Open Access Journals (Sweden)

    Morawetz R.A.

    1998-01-01

    Full Text Available The contributions of cytokines to the development and progression of disease in a mouse model of retrovirus-induced immunodeficiency (MAIDS are controversial. Some studies have indicated an etiologic role for type 2 cytokines, while others have emphasized the importance of type 1 cytokines. We have used mice deficient in expression of IL-4, IL-10, IL-4 and IL-10, IFN-g, or ICSBP - a transcriptional protein involved in IFN signaling - to examine their contributions to this disorder. Our results demonstrate that expression of type 2 cytokines is an epiphenomenon of infection and that IFN-g is a driving force in disease progression. In addition, exogenously administered IL-12 prevents many manifestations of disease while blocking retrovirus expression. Interruption of the IFN signaling pathways in ICSBP-/- mice blocks induction of MAIDS. Predictably, ICSBP-deficient mice exhibit impaired responses to challenge with several other viruses. This immunodeficiency is associated with impaired production of IFN-g and IL-12. Unexpectedly, however, the ICSBP-/- mice also develop a syndrome with many similarities to chronic myelogenous leukemia in humans. The chronic phase of this disease is followed by a fatal blast crisis characterized by clonal expansions of undifferentiated cells. ICSBP is thus an important determinant of hematopoietic growth and differentiation as well as a prominent signaling molecule for IFNs

  6. Interplay of cytokines in preterm birth

    Directory of Open Access Journals (Sweden)

    Monika Pandey

    2017-01-01

    Full Text Available Preterm infants (i.e., born before <37 wk of gestation are at increased risk of morbidity and mortality and long-term disabilities. Global prevalence of preterm birth (PTB varies from 5 to 18 per cent. There are multiple aetiological causes and factors associated with PTB. Intrapartum infections are conventionally associated with PTB. However, maternal genotype modulates response to these infections. This review highlights the association of cytokine gene polymorphisms and their levels with PTB. Varying PTB rates across the different ethnic groups may be as a result of genetically mediated varying cytokines response to infections. Studies on genetic variations in tumour necrosis factor-alpha, interleukin-1 alpha (IL-1α, IL-1β, IL-6, IL-10 and toll-like receptor-4 genes and their association with PTB, have been reviewed. No single polymorphism of the studied genes was found to be associated with PTB. However, increased maternal levels of IL-1β and IL-6 and low levels of IL-10 have been found to be associated with PTB.

  7. Angiogenic Factors and Cytokines in Diabetic Retinopathy

    Science.gov (United States)

    Abcouwer, Steven F.

    2013-01-01

    Diabetic retinopathy (DR) is a sight-threatening complication of both type-1 and type-2 diabetes. The recent success of treatments inhibiting the function of vascular endothelial growth factor (VEGF) demonstrates that specific targeting of a growth factor responsible for vascular permeability and growth is an effective means of treating DR-associated vascular dysfunction, edema and angiogenesis. This has stimulated research of alternative therapeutic targets involved in the control of retinal vascular function. However, additional treatment options and preventative measures are still needed and these require a greater understanding of the pathological mechanisms leading to the disturbance of retinal tissue homeostasis in DR. Although severe DR can be treated as a vascular disease, abundant data suggests that inflammation is also occurring in the diabetic retina.Thus, anti-inflammatory therapies may also be useful for treatment and prevention of DR. Herein, the evidence for altered expression of angiogenic factors and cytokines in DR is reviewed and possible mechanisms by which the expression of VEGF and cytokines may be increased in the diabetic retina are examined. In addition, the potential role for microglial activation in diabetic retinal neuroinflammation is explored. PMID:24319628

  8. 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

  9. Large-scale bedforms induced by supercritical flows and wave-wave interference in the intertidal zone (Cap Ferret, France)

    Science.gov (United States)

    Vaucher, Romain; Pittet, Bernard; Humbert, Thomas; Ferry, Serge

    2017-11-01

    The Cap Ferret sand spit is situated along the wave-dominated, tidally modulated Atlantic coast of western France, characterized by a semidiurnal macrotidal range. It displays peculiar dome-like bedforms that can be observed at low tide across the intertidal zone. These bedforms exhibit a wavelength of ca. 1.2 m and an elevation of ca. 30 cm. They occur only when the incident wave heights reach 1.5-2 m. The internal stratifications are characterized by swaley-like, sub-planar, oblique-tangential, oblique-tabular, as well as hummocky-like stratifications. The tabular and tangential stratifications comprise prograding oblique sets (defined as foresets and backsets) that almost always show variations in their steepness. Downcutting into the bottomsets of the oblique-tangential stratifications is common. The sets of laminae observed in the bedforms share common characteristics with those formed by supercritical flows in flume experiments of earlier studies. These peculiar bedforms are observed at the surf-swash transition zone where the backwash flow reaches supercritical conditions. This type of flow can explain their internal architecture but not their general dome-like (three-dimensional) morphology. Wave-wave interference induced by the geomorphology (i.e. tidal channel) of the coastal environment is proposed as explanation for the localized formation of such bedforms. This study highlights that the combination of supercritical flows occurring in the surf-swash transition zone and wave-wave interferences can generate dome-like bedforms in intertidal zones.

  10. 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.

  11. Aspergillus Cell Wall Chitin Induces Anti- and Proinflammatory Cytokines in Human PBMCs via the Fc-γ Receptor/Syk/PI3K Pathway

    Science.gov (United States)

    Becker, K. L.; Aimanianda, V.; Wang, X.; Gresnigt, M. S.; Ammerdorffer, A.; Jacobs, C. W.; Gazendam, R. P.; Joosten, L. A. B.; Netea, M. G.

    2016-01-01

    ABSTRACT Chitin is an important cell wall component of Aspergillus fumigatus conidia, of which hundreds are inhaled on a daily basis. Previous studies have shown that chitin has both anti- and proinflammatory properties; however the exact mechanisms determining the inflammatory signature of chitin are poorly understood, especially in human immune cells. Human peripheral blood mononuclear cells were isolated from healthy volunteers and stimulated with chitin from Aspergillus fumigatus. Transcription and production of the proinflammatory cytokine interleukin-1β (IL-1β) and the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1Ra) were measured from the cell culture supernatant by quantitative PCR (qPCR) or enzyme-linked immunosorbent assay (ELISA), respectively. Chitin induced an anti-inflammatory signature characterized by the production of IL-1Ra in the presence of human serum, which was abrogated in immunoglobulin-depleted serum. Fc-γ-receptor-dependent recognition and phagocytosis of IgG-opsonized chitin was identified as a novel IL-1Ra-inducing mechanism by chitin. IL-1Ra production induced by chitin was dependent on Syk kinase and phosphatidylinositol 3-kinase (PI3K) activation. In contrast, costimulation of chitin with the pattern recognition receptor (PRR) ligands lipopolysaccharide, Pam3Cys, or muramyl dipeptide, but not β-glucan, had synergistic effects on the induction of proinflammatory cytokines by human peripheral blood mononuclear cells (PBMCs). In conclusion, chitin can have both pro- and anti-inflammatory properties, depending on the presence of pathogen-associated molecular patterns and immunoglobulins, thus explaining the various inflammatory signatures reported for chitin. PMID:27247234

  12. Effect of Intravenous immunoglobulin on Th1 and Th2 lymphocytes and improvement of pregnancy outcome in recurrent pregnancy loss (RPL).

    Science.gov (United States)

    Ahmadi, Majid; Abdolmohammadi-Vahid, Samaneh; Ghaebi, Mahnaz; Aghebati-Maleki, Leili; Afkham, Amir; Danaii, Shahla; Abdollahi-Fard, Sedigheh; Heidari, Lida; Jadidi-Niaragh, Farhad; Younesi, Vahid; Nouri, Mohammad; Yousefi, Mehdi

    2017-08-01

    Women with elevated natural killer (NK) cell frequency and function during pregnancy, suffer from recurrent pregnancy loss (RPL). In the present study, the possible effect of intravenous immunoglobulin (IVIG) administration on Th1 and Th2 cell frequency, cytokine secretion, and expression of transcription factors is compared between RPL patients and control group. Totally, 44 women with a history of RPL (32 women as treated group and 12 as control group) were enrolled in the study. The frequency of Th1 and Th2 lymphocytes, the expression of transcription factors related to these cells and the serum levels of associated cytokines were assessed by flowcytometry, real-time PCR and ELISA, respectively. All, assessments were performed both before and after treatment with IVIG. A significant reduction in Th1 lymphocyte frequency, transcription factor expression and cytokine levels were observed in IVIG-treated group, while all the above parameters indicated a significant increase for Th2 lymphocytes. Th1/Th2 ratio decreased significantly (p value<0.0001) at the end of treatment and 28 out of 32 (87.5%) women in IVIG-treated group had live birth in comparison with 5 out of 12 (41.6%) in untreated group. IVIG administration proves to be an efficient therapeutic strategy which is able to enhance the success rate of pregnancy through a shift in Th2 responses. Furthermore, IVIG presents efficacy for the treatment of reproduction failures especially in subjects with immune cell abnormalities and increased NK cell level and function. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Biased immunoglobulin light chain gene usage in the shark1

    Science.gov (United States)

    Iacoangeli, Anna; Lui, Anita; Naik, Ushma; Ohta, Yuko; Flajnik, Martin; Hsu, Ellen

    2015-01-01

    This study of a large family of kappa light (L) chain clusters in nurse shark completes the characterization of its classical immunoglobulin (Ig) gene content (two heavy chain classes, mu and omega, and four L chain isotopes, kappa, lambda, sigma, and sigma-2). The shark kappa clusters are minigenes consisting of a simple VL-JL-CL array, where V to J recombination occurs over a ~500 bp interval, and functional clusters are widely separated by at least 100 kb. Six out of ca. 39 kappa clusters are pre-rearranged in the germline (GL-joined). Unlike the complex gene organization and multistep assembly process of Ig in mammals, each shark Ig rearrangement, somatic or in the germline, appears to be an independent event localized to the minigene. This study examined the expression of functional, non-productive, and sterile transcripts of the kappa clusters compared to the other three L chain isotypes. Kappa cluster usage was investigated in young sharks, and a skewed pattern of split gene expression was observed, one similar in functional and non-productive rearrangements. These results show that the individual activation of the spatially distant kappa clusters is non-random. Although both split and GL-joined kappa genes are expressed, the latter are prominent in young animals and wane with age. We speculate that, in the shark, the differential activation of the multiple isotypes can be advantageously used in receptor editing. PMID:26342033

  14. Serum immunoglobulins E are related to menstrual cycle

    International Nuclear Information System (INIS)

    Vellutini, Mariella; Viegi, Giovanni; Parrini, Donatella; Pedreschi, Marzia; Baldacci, Sandra; Modena, Paola; Biavati, Batrizia; Simoni, Marzia; Carrozzi, Laura; Giuntini, Carlo

    1997-01-01

    During a cross sectional epidemiological survey on a general population sample, 596 fertile women underwent total serum IgE determination. They completed an interviewer-administered standardized questionnaire and were categorized according to their menstrual period. They were divided into two groups: those from days 10 to 20, who were considered to be in the periovulatory phase, and those in the other phases. IgE mean values were significantly different (p = 0.01) in the two groups: particularly, lower IgE values were found in those in periovulatory phase, after accounting for smoking habit and atopic status. By multiple regression analysis, taking into account the independent effects of menstrual period, age, smoking habit, hours of fast, skin prick test reactivity and presence of cough, significantly lower IgE values in the periovulatory phase were found. We hypothesize the possibility that a decrease of IgE concentration occurs during midcycle: a reduced immune response might facilitate the ovuli implantation. Further studies are necessary to longitudinally investigate the trend of IgE in the same women, as well as the distributions and the trends of other immunoglobulins

  15. Imaging findings of primary immunoglobulin G4-related cervical lymphadenopathy

    Energy Technology Data Exchange (ETDEWEB)

    Kawaguchi, Masaya; Kato, Hiroki; Goshima, Satoshi; Matsuo, Masayuki [Gifu University School of Medicine, Department of Radiology, Gifu (Japan); Kito, Yusuke [Gifu University School of Medicine, Department of Pathology and Translational Research, Gifu (Japan); Mizuta, Keisuke; Aoki, Mitsuhiro [Gifu University School of Medicine, Department of Otolaryngology, Gifu (Japan); Kato, Keizo [Gifu University School of Medicine, Department of Oral and Maxillofacial Sciences, Gifu (Japan)

    2017-11-15

    The purpose of the present study was to assess imaging findings of primary immunoglobulin G4 (IgG4)-related cervical lymphadenopathy. Five consecutive patients with clinically, serologically, and histopathologically confirmed primary IgG4-related cervical lymphadenopathy without any other organ involvement were included. All patients underwent contrast-enhanced computed tomography (CT), and four underwent {sup 18}F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT. We retrospectively reviewed the images and assessed the number, size, location, central necrosis, perinodal infiltration, penetrating vessels, and maximum standardized uptake values (SUVmax) of the enlarged cervical nodes. Thirteen enlarged cervical nodes measuring larger than 10 mm in minimum diameter were identified. The maximum and minimum diameter of enlarged nodes ranged from 1.2 to 3.2 cm (median, 1.8 cm) and from 1.0 to 1.9 cm (median, 1.2 cm), respectively. Lymphadenopathy was unilateral in all patients, and eight enlarged nodes were located at level IB (62%), one at level II (8%), three at level IV (23%), and one at level V (8%). Central necrosis was not seen in any nodes. Perinodal infiltration was seen in only one node (8%), and penetrating vessels were seen in seven nodes (54%). The median SUVmax of nine nodes was 4.45 (range, 2.08-12.44). Eight enlarged nodes (62%) were located in the submandibular region. Central necrosis was not observed in any nodes and perinodal infiltration was observed in one node (8%). (orig.)

  16. Clinical outcomes of intravenous immunoglobulin therapy in refractory uveitis.

    Science.gov (United States)

    Garcia-Geremias, M; Carreño, E; Epps, S J; Lee, R W J; Dick, A D

    2015-04-01

    Intravenous immunoglobulin (IVIg) therapy has multiple mechanisms of immunomodulatory action. We wished therefore to assess its efficacy in a spectrum of patients with refractory uveitis. Retrospective review of clinical charts was conducted to document response to IVIg treatment in consecutive patients with treatment-refractory uveitis. Main outcome measures were control of intraocular inflammation, visual acuity, progression of the disease, and complications. Four (two male) patients, with a mean age at the beginning of the treatment of 47 years (range: 39-64), were included in the study. Indication for treatment was patients with active non-infectious uveitis refractory to steroids and immunomodulatory therapy. All patients received a course of 0.5 g/kg per day of IVIg for three consecutive days, repeating this course at a mean of 11 week (range: 2-39 weeks) intervals when indicated clinically. The median duration of the IVIg therapy was 7 months (range: 3-14 months). In three patients treatment resulted in stabilisation and prevention of progression of the disease, and additionally in two patients it facilitated a decrease in prednisolone dose. Treatment failed to induce long-term remission in one patient with recurrence of macular oedema. IVIg was well tolerated with neither immediate nor longer-term adverse events observed. In three out of four cases IVIg was an effective adjunctive therapy and well tolerated for the management of treatment-refractory uveitis.

  17. Natural immunoglobulins (contribution to a debate on biomedical education

    Directory of Open Access Journals (Sweden)

    Vaz Nelson M

    2000-01-01

    Full Text Available Immunology has contributed to biomedical education in many important ways since the creation of scientific medicine in the last quarter of the 19th century. Today, immunology is a major area of biomedical research. Nevertheless, there are many basic problems unresolved in immunological activities and phenomena. Solving these problems is probably necessary to devise predictable and safe ways to produce new vaccines, treat allergy and autoimmune diseases and perform safe transplants. This challenge involves not only technical developments but also changes in attitude, of which the most fundamental is to abandon the traditional stimulus-response perspective in favor of more "systemic" views. Describing immunological activities as the operation of a complex multiconnected network, raises biological and epistemological issues not usually dealt with in biomedical education. Here we point to one example of systemic approaches. A new form of immunoblot (Panama blot, by which the reaction of natural immunoglobulins with complex protein mixtures may be analyzed by a special software and multivariate statistics, has been recently used to characterize human autoimmune diseases. Our preliminary data show that Panama blots can also be used to characterize global (systemic immunogical changes in chronic human parasitic diseases, such as malaria and schistosomiasis mansoni, that correlate with the clinical status.

  18. [Batch release of immunoglobulin and monoclonal antibody products].

    Science.gov (United States)

    Gross, S

    2014-10-01

    The Paul-Ehrlich Institute (PEI) is an independent institution of the Federal Republic of Germany responsible for performing official experimental batch testing of sera. The institute decides about the release of each batch and performs experimental research in the field. The experimental quality control ensures the potency of the product and also the absence of harmful impurities. For release of an immunoglobulin batch the marketing authorization holder has to submit the documentation of the manufacture and the results of quality control measures together with samples of the batch to the PEI. Experimental testing is performed according to the approved specifications regarding the efficacy and safety. Since implementation of the 15th German drug law amendment, the source of antibody is not defined anymore. According to § 32 German drug law, all batches of sera need to be released by an official control laboratory. Sera are medicinal products, which contain antibodies, antibody fragments or fusion proteins with a functional antibody portion. Therefore, all batches of monoclonal antibodies and derivatives must also be released by the PEI and the marketing authorization holder has to submit a batch release application. Under certain circumstances a waiver for certain products can be issued with regard to batch release. The conditions for such a waiver apply to the majority of monoclonal antibodies.

  19. Effect of radioiodine on stimulatory activity of Graves' immunoglobulins

    International Nuclear Information System (INIS)

    Atkinson, S.; McGregor, A.M.; Kendall-Taylor, P.; Peterson, M.M.; Smith, B.R.

    1982-01-01

    The effects of 131 I therapy on the activity of thyroid stimulating antibody (TSAb) and thyrotrophin binding inhibiting immunoglobulin (TBII) in nineteen patients with Graves' disease have been studied. Prior to 131 I administration, TSAb was detected in 84%, and TBII in 68% of patients. Following 131 I administration TSAb and TBII were detectable in 100% of patients. The elevation 3 months after treatment of the means of both the TSAb and TBII indices for the group of nineteen patients was highly significant compared with pretreatment values. All the patients went into remission during the course of the study and the TSAb index declined in all patients, becoming undetectable in eleven; TBII also declined in most patients but remained detectable in thirteen. The study furthermore afforded the opportunity for a direct comparison of binding with stimulatory activity. These results show that after 131 I therapy for Graves' hyperthyroidism there is a transient increase in TSAb as well as TBII, followed by a decline, and that the measurement of binding and stimulatory activities are in good general agreement. (author)

  20. Glycosylation of immunoglobulin A influences its receptor binding.

    Science.gov (United States)

    Basset, C; Devauchelle, V; Durand, V; Jamin, C; Pennec, Y L; Youinou, P; Dueymes, M

    1999-12-01

    Immunoglobulin A (IgA), which is heavily glycosylated, interacts with a variety of receptors, e.g. the asialoglycoprotein receptor (ASGP-R), which binds terminal galactose residues, and the Fcalpha receptor (FcalphaRI). It has thus been proposed that elevated serum levels of IgA in primary Sjögren's syndrome (pSS) are caused by its defective clearance. To test this hypothesis, we developed a method (based on sialyl transferases eluted from a hepatoma cell line) to increase the amount of sialic acid (SA) on IgA, and used a battery of IgA1- and IgA2-specific glycosidases to reduce this amount. Binding of IgA1 and IgA2 to ASGP-R and FcalphaRI was found to be sugar dependent because oversialylated IgA bound less than native or desialylated IgA. However, individual sugars did not play a direct role in this binding. Given that IgA are oversialylated in pSS, defective clearance of IgA may indeed be ascribed to an excess of SA in IgA1 and IgA2.

  1. Ikaros controls isotype selection during immunoglobulin class switch recombination.

    Science.gov (United States)

    Sellars, MacLean; Reina-San-Martin, Bernardo; Kastner, Philippe; Chan, Susan

    2009-05-11

    Class switch recombination (CSR) allows the humoral immune response to exploit different effector pathways through specific secondary antibody isotypes. However, the molecular mechanisms and factors that control immunoglobulin (Ig) isotype choice for CSR are unclear. We report that deficiency for the Ikaros transcription factor results in increased and ectopic CSR to IgG(2b) and IgG(2a), and reduced CSR to all other isotypes, regardless of stimulation. Ikaros suppresses active chromatin marks, transcription, and activation-induced cytidine deaminase (AID) accessibility at the gamma2b and gamma2a genes to inhibit class switching to these isotypes. Further, Ikaros directly regulates isotype gene transcription as it directly binds the Igh 3' enhancer and interacts with isotype gene promoters. Finally, Ikaros-mediated repression of gamma2b and gamma2a transcription promotes switching to other isotype genes by allowing them to compete for AID-mediated recombination at the single-cell level. Thus, our results reveal transcriptional competition between constant region genes in individual cells to be a critical and general mechanism for isotype specification during CSR. We show that Ikaros is a master regulator of this competition.

  2. Imaging findings of primary immunoglobulin G4-related cervical lymphadenopathy

    International Nuclear Information System (INIS)

    Kawaguchi, Masaya; Kato, Hiroki; Goshima, Satoshi; Matsuo, Masayuki; Kito, Yusuke; Mizuta, Keisuke; Aoki, Mitsuhiro; Kato, Keizo

    2017-01-01

    The purpose of the present study was to assess imaging findings of primary immunoglobulin G4 (IgG4)-related cervical lymphadenopathy. Five consecutive patients with clinically, serologically, and histopathologically confirmed primary IgG4-related cervical lymphadenopathy without any other organ involvement were included. All patients underwent contrast-enhanced computed tomography (CT), and four underwent 18 F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT. We retrospectively reviewed the images and assessed the number, size, location, central necrosis, perinodal infiltration, penetrating vessels, and maximum standardized uptake values (SUVmax) of the enlarged cervical nodes. Thirteen enlarged cervical nodes measuring larger than 10 mm in minimum diameter were identified. The maximum and minimum diameter of enlarged nodes ranged from 1.2 to 3.2 cm (median, 1.8 cm) and from 1.0 to 1.9 cm (median, 1.2 cm), respectively. Lymphadenopathy was unilateral in all patients, and eight enlarged nodes were located at level IB (62%), one at level II (8%), three at level IV (23%), and one at level V (8%). Central necrosis was not seen in any nodes. Perinodal infiltration was seen in only one node (8%), and penetrating vessels were seen in seven nodes (54%). The median SUVmax of nine nodes was 4.45 (range, 2.08-12.44). Eight enlarged nodes (62%) were located in the submandibular region. Central necrosis was not observed in any nodes and perinodal infiltration was observed in one node (8%). (orig.)

  3. [Identification and production of monoclonal antibody of Siberian tiger's immunoglobulin].

    Science.gov (United States)

    Zhang, Yaonglong; Zhang, Duanling; Zhou, Ming; Xue, Yuan; Hua, Yuping; Ma, Jianzhang

    2010-03-01

    To purify immunoglobulin (Ig) of Siberian Tiger and prepare monoclonal antibody (mAb) against the Ig,which can be used to develop immunological diagnostic kits for diagnosing infectious disease in Siberian Tiger. The Ig of Siberian tigers was purified with saturated ammonium sulfate combined with recombinant Protein G. The C57BL/6 mice were immunized with the purified Ig. Spleno-cytes of the mice immunized were collected and fused with the mouse myeloma cell line (Sp2/0-Ag14). The positive hybridoma clones were selected by ELISA and were identified by western blot. The sandwich ELISA was used to detect immunocompetence of the purified Ig and the mAb. We obtained three mouse hybridoma clones that produced mAbs against Ig of Siberian Tiger. The derived McAbs could recognize Ig heavy chain of Siberian Tiger specifically. The biological activity of the Ig and obtained McAbs also could be identified by detecting the antibody induced by panleukopenia virus (FPV-HLJ) vaccine in Siberian Tiger. The antibody also would be useful for assess the vaccine efficacy against the infectious disease on the Siberian Tiger. Protein G can be used in Ig purification of Siberian Tiger. The obtained McAbs from the hybridoma ADT11 in this study owned strong ability to bind Ig of Siberian Tiger and have a stable immunocompetence. They can be used to develop diagnostic methods for detecting infectious disease in Siberian Tiger and vaccine research.

  4. Gut microbiota utilize immunoglobulin A for mucosal colonization.

    Science.gov (United States)

    Donaldson, G P; Ladinsky, M S; Yu, K B; Sanders, J G; Yoo, B B; Chou, W-C; Conner, M E; Earl, A M; Knight, R; Bjorkman, P J; Mazmanian, S K

    2018-05-18

    The immune system responds vigorously to microbial infection while permitting lifelong colonization by the microbiome. Mechanisms that facilitate the establishment and stability of the gut microbiota remain poorly described. We found that a regulatory system in the prominent human commensal Bacteroides fragilis modulates its surface architecture to invite binding of immunoglobulin A (IgA) in mice. Specific immune recognition facilitated bacterial adherence to cultured intestinal epithelial cells and intimate association with the gut mucosal surface in vivo. The IgA response was required for B. fragilis (and other commensal species) to occupy a defined mucosal niche that mediates stable colonization of the gut through exclusion of exogenous competitors. Therefore, in addition to its role in pathogen clearance, we propose that IgA responses can be co-opted by the microbiome to engender robust host-microbial symbiosis. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  5. Chemical stabilization of porous silicon for enhanced biofunctionalization with immunoglobulin

    Directory of Open Access Journals (Sweden)

    Nelson Naveas, Vicente Torres Costa, Dario Gallach, Jacobo Hernandez-Montelongo, Raul Jose Martín Palma, Josefa Predenstinacion Garcia-Ruiz and Miguel Manso-Silván

    2012-01-01

    Full Text Available Porous silicon (PSi is widely used in biological experiments, owing to its biocompatibility and well-established fabrication methods that allow tailoring its surface. Nevertheless, there are some unresolved issues such as deciding whether the stabilization of PSi is necessary for its biological applications and evaluating the effects of PSi stabilization on the surface biofunctionalization with proteins. In this work we demonstrate that non-stabilized PSi is prone to detachment owing to the stress induced upon biomolecular adsorption. Biofunctionalized non-stabilized PSi loses the interference properties characteristic of a thin film, and groove-like structures resulting from a final layer collapse were observed by scanning electron microscopy. Likewise, direct PSi derivatization with 3-aminopropyl-triethoxysilane (APTS does not stabilize PSi against immunoglobulin biofunctionalization. To overcome this problem, we developed a simple chemical process of stabilizing PSi (CoxPSi for biological applications, which has several advantages over thermal stabilization (ToxPSi. The process consists of chemical oxidation in H2O2, surface derivatization with APTS and a curing step at 120 °C. This process offers integral homogeneous PSi morphology, hydrophilic surface termination (contact angle θ = 26° and highly efficient derivatized and biofunctionalized PSi surfaces (six times more efficient than ToxPSi. All these features are highly desirable for biological applications, such as biosensing, where our results can be used for the design and optimization of the biomolecular immobilization cascade on PSi surfaces.

  6. Importance of neonatal immunoglobulin transfer for hippocampal development and behaviour in the newborn pig.

    Directory of Open Access Journals (Sweden)

    Kateryna Goncharova

    Full Text Available Neurological disorders are among the main clinical problems affecting preterm children and often result in the development of communication and learning disabilities later in life. Several factors are of importance for brain development, however the role of immunoglobulins (passive immunity transfer has not yet been investigated. Piglets are born agammaglobulinemic, as a result of the lack of transfer of maternal immunoglobulins in utero, thus, they serve as an ideal model to mimic the condition of immunoglobulin deficiency in preterm infants. Thirty six, unsuckled newborn piglets were fed an infant formula or colostrum and supplemented orally or intravenously with either species-specific or foreign immunoglobulin and then compared to both newborn and sow-reared piglets. Two days after the piglets were born behavioural tests (novel recognition and olfactory discrimination of conspecifics scent were performed, after which the piglets were sacrificed and blood, cerebrospinal fluid and hippocampi samples were collected for analyses. Both parameters of neuronal plasticity (neuronal maturation and synapse-associated proteins and behavioural test parameters appeared to be improved by the appearance of species-specific porcine immunoglulin in the circulation and cerebrospinal fluid of the piglets. In conclusion, we postulate possible positive clinical effects following intravenous infusion of human immunoglobulin in terms of neuronal plasticity and cognitive function in preterm infants born with low blood immunoglobulin levels.

  7. Optimized localization of bacterial infections with technetium-99m labelled human immunoglobulin after protein charge selection

    International Nuclear Information System (INIS)

    Welling, M.; Feitsma, H.I.J.; Calame, W.; Ensing, G.J.; Goedemans, W.; Pauwels, E.K.J.

    1994-01-01

    To improve the scintigraphic detection of bacterial infections a protein charge-purified fraction of polyclonal human immunoglobulin was applied as a radiopharmaceutical. This purification was achieved by attaching the immunoglobulin to an anion-exchanger column and by obtaining the column-bound fraction with buffer. The binding to bacteria in vitro and the target to non-target ratios of an experimental thigh infection with Staphylococcus aureus or Klebsiella pneumoniae in mice were evaluated to compare the purified and the unpurified immunoglobulin. The percentage of binding to all gram-positive and gram-negative bacteria used in this study was significantly (P 99m Tc-labelled protein charge-purified polyclonal human immunoglobulin was administered intravenously. At all time intervals the target (infected thighs) to non-target (non-infected thighs) ratios for both infections were significantly higher (P 99m Tc-labelled protein charge-purified immunoglobulin localizes both a gram-positive and a gram-negative thigh infection more intensely and faster than 99m Tc-labelled unpurified immunoglobulin. (orig.)

  8. Cytokine genes as potential biomarkers for muscle weakness in OPMD

    DEFF Research Database (Denmark)

    Riaz, Muhammad; Raz, Yotam; van der Slujis, Barbara

    2016-01-01

    is a dominant, late-onset myopathy, caused by an alanine-expansion mutation in the gene encoding for poly(A) binding protein nuclear 1 (expPABPN1). Here, we investigated the hypothesis that cytokines could mark OPMD disease state. We determined cytokines levels the vastus lateralis muscle from genetically...... confirmed expPABPN1 carriers at a symptomatic or a presymptomatic stage. We identified cytokine-related genes candidates from a transcriptome study in a mouse overexpressing exp PABPN1 Six cytokines were found to be consistently down-regulated in OPMD vastus lateralis muscles. Expression levels...

  9. Characterization and potential clinical applications of autoantibodies against cytokines

    DEFF Research Database (Denmark)

    de Lemos Rieper, Carina; Galle, Pia; Hansen, Morten Bagge

    2009-01-01

    Autoantibodies recognizing cytokines arise in certain patients during the course of therapy with recombinant cytokines, although they may arise spontaneously as well. They are typically high avidity and in vitro neutralizing IgG antibodies present in picomolar to nanomolar concentrations. Methodo......Autoantibodies recognizing cytokines arise in certain patients during the course of therapy with recombinant cytokines, although they may arise spontaneously as well. They are typically high avidity and in vitro neutralizing IgG antibodies present in picomolar to nanomolar concentrations...

  10. Inflammatory cytokines and immune system modulation by aerobic ...

    African Journals Online (AJOL)

    Keywords: Immune function, inflammatory cytokines, aerobic exercise, resistance exercise, aging. ... Physical exercise is effective in reducing (or ameliorate) the ..... moderate resistance training program increases muscle .... Nutrition Metabo-.

  11. Cytokine ratios in chronic periodontitis and type 2 diabetes mellitus.

    Science.gov (United States)

    Acharya, Anirudh B; Thakur, Srinath; Muddapur, M V; Kulkarni, Raghavendra D

    Chronic periodontitis may influence systemic cytokines in type 2 diabetes. This study aimed to evaluate the cytokine ratios in type 2 diabetes with, and without chronic periodontitis. Gingival status, periodontal, glycemic parameters and serum cytokines were evaluated in participants grouped as healthy, chronic periodontitis, and type 2 diabetes with, and without chronic periodontitis. Cytokine ratios showed significant differences in type 2 diabetes and chronic periodontitis, were highest in participants having both type 2 diabetes and chronic periodontitis, with a statistically significant cut-off point and area under curve by receiver operating characteristic. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  12. Monoclonal antibodies to snakehead, Channa striata immunoglobulins: detection and quantification of immunoglobulin-positive cells in blood and lymphoid organs.

    Science.gov (United States)

    Sood, Neeraj; Chaudhary, Dharmendra K; Rathore, Gaurav; Singh, Akhilesh; Lakra, W S

    2011-02-01

    Snakehead Channa striata is an important freshwater food fish in many Southeast Asian countries. Three monoclonal antibodies (C9, C10 and D10) were developed against purified serum immunoglobulins of Channa striata (Cs-Ig) and characterized. C9 and D10 MAbs were specific to heavy chain, while C10 MAb detected only unreduced Cs-Ig in western blotting. In competitive ELISA, C9 and C10 MAbs were specific to C. striata Ig and showed no cross reactivity with serum Ig of other fish species i.e. Channa punctatus, Channa marulius, Clarias batrachus and Labeo rohita. D10 MAb showed reactivity to serum Ig of C. striata and C. marulius. In FACS analysis of gated lymphocytes, the percentage of Ig+ cells detected by C9 MAb was 18.2%, 27.7% and 10.3% in blood, spleen and kidney, respectively (n=3, body weight 500-600 g). However, only a few cells (0.5%) were found to be Ig+ in thymus (n=5). C9 MAb was also successfully employed to demonstrate Ig+ cells in blood smears and formalin fixed sections of spleen and kidney. These findings suggest that the spleen plays an important role in humoral immunity as compared to head kidney. Further, these MAbs can be useful immunological tool in monitoring health status of cultured C. striata. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Evaluation of synthetic infection-enhancing lipopeptides as adjuvants for a live-attenuated canine distemper virus vaccine administered intra-nasally to ferrets.

    Science.gov (United States)

    Nguyen, D Tien; Ludlow, Martin; van Amerongen, Geert; de Vries, Rory D; Yüksel, Selma; Verburgh, R Joyce; Osterhaus, Albert D M E; Duprex, W Paul; de Swart, Rik L

    2012-07-20

    Inactivated paramyxovirus vaccines have been associated with hypersensitivity responses upon challenge infection. For measles and canine distemper virus (CDV) safe and effective live-attenuated virus vaccines are available, but for human respiratory syncytial virus and human metapneumovirus development of such vaccines has proven difficult. We recently identified three synthetic bacterial lipopeptides that enhance paramyxovirus infections in vitro, and hypothesized these could be used as adjuvants to promote immune responses induced by live-attenuated paramyxovirus vaccines. Here, we tested this hypothesis using a CDV vaccination and challenge model in ferrets. Three groups of six animals were intra-nasally vaccinated with recombinant (r) CDV(5804P)L(CCEGFPC) in the presence or absence of the infection-enhancing lipopeptides Pam3CSK4 or PHCSK4. The recombinant CDV vaccine virus had previously been described to be over-attenuated in ferrets. A group of six animals was mock-vaccinated as control. Six weeks after vaccination all animals were challenged with a lethal dose of rCDV strain Snyder-Hill expressing the red fluorescent protein dTomato. Unexpectedly, intra-nasal vaccination of ferrets with rCDV(5804P)L(CCEGFPC) in the absence of lipopeptides resulted in good immune responses and protection against lethal challenge infection. However, in animals vaccinated with lipopeptide-adjuvanted virus significantly higher vaccine virus loads were detected in nasopharyngeal lavages and peripheral blood mononuclear cells. In addition, these animals developed significantly higher CDV neutralizing antibody titers compared to animals vaccinated with non-adjuvanted vaccine. This study demonstrates that the synthetic cationic lipopeptides Pam3CSK4 and PHCSK4 not only enhance paramyxovirus infection in vitro, but also in vivo. Given the observed enhancement of immunogenicity their potential as adjuvants for other live-attenuated paramyxovirus vaccines should be considered

  14. 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

  15. 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.

  16. Cytokines and Angiogenesis in the Corpus Luteum

    Directory of Open Access Journals (Sweden)

    António M. Galvão

    2013-01-01

    Full Text Available In adults, physiological angiogenesis is a rare event, with few exceptions as the vasculogenesis needed for tissue growth and function in female reproductive organs. Particularly in the corpus luteum (CL, regulation of angiogenic process seems to be tightly controlled by opposite actions resultant from the balance between pro- and antiangiogenic factors. It is the extremely rapid sequence of events that determines the dramatic changes on vascular and nonvascular structures, qualifying the CL as a great model for angiogenesis studies. Using the mare CL as a model, reports on locally produced cytokines, such as tumor necrosis factor α (TNF, interferon gamma (IFNG, or Fas ligand (FASL, pointed out their role on angiogenic activity modulation throughout the luteal phase. Thus, the main purpose of this review is to highlight the interaction between immune, endothelial, and luteal steroidogenic cells, regarding vascular dynamics/changes during establishment and regression of the equine CL.

  17. Oral administration of Saccharomyces boulardii alters duodenal morphology, enzymatic activity and cytokine production response in broiler chickens.

    Science.gov (United States)

    Sun, Yajing; Rajput, Imran Rashid; Arain, Muhammad Asif; Li, Yanfei; Baloch, Dost Muhammad

    2017-08-01

    The present study evaluated the effects of Saccharomyces boulardii on duodenal digestive enzymes, morphology and cytokine induction response in broiler chicken. A total of 200 birds were allotted into two groups (n = 100) and each group divided into five replications (n = 20). The control group was fed basal diet in addition to antibiotic (virginiamycin 20 mg/kg), and treatment group received (1 × 10 8  colony-forming units/kg feed) S. boulardii in addition to basal diet lasting for 72 days. The results compared to control group revealed that adenosine triphosphatase, gamma glutamyl transpeptidase, lipase and trypsin activities were higher, while, no significant improvement was observed in amylase activities in the duodenum of the treatment group. Moreover, morphological findings showed that villus height, width and number of goblet cells markedly increased. Additionally, transmission electron microscopy visualized that villus height, width and structural condensation significantly increased in the treatment group. The immunohistological observations showed increased numbers of immunoglobulin A (IgA)-positive cells in the duodenum of the treatment group. Meanwhile, cytokine production levels of tumor necrosis factor-α, interleukin (IL)-10, transforming growth factor-β and secretory IgA markedly increased, and IL-6 statistically remained unchanged as compared to the control group. These findings illustrated that initial contact of S. boulardii to the duodenum has significant impact in improving enzymatic activity, intestinal morphology and cytokine response in broiler chicken. © 2016 Japanese Society of Animal Science.

  18. Immunoparesis and polyclonal immunoglobulin recovery after auto-SCT for patients with multiple myeloma treated at a single institution.

    Science.gov (United States)

    Jimenez-Zepeda, Victor H; Duggan, Peter; Neri, Paola; Chaudhry, Ahsan; Tay, Jason; Bahlis, Nizar

    2017-11-21

    Immunoparesis and polyclonal immunoglobulin recovery have been recently described as common indicators of immune dysfunction in patients with multiple myeloma. In the present study, we aimed to assess the impact of immunoparesis and polyclonal immunoglobulin recovery at day-100 post autologous stem cell transplant (auto-SCT) on clinical outcomes. A total of 302 patients were included for the analysis of immunoparesis, and 197 were evaluable for polyclonal immunoglobulin recovery evaluation. Immunoparesis was observed in 93.5% of cases, with 47% of cases having polyclonal immunoglobulin recovery at 12 months post auto-SCT. Median overall and progression-free survival were longer in the group of patients with complete or partial normalization of polyclonal immunoglobulins. Patients receiving consolidation had a lower level of polyclonal reconstitution. In conclusion, polyclonal immunoglobulin recovery by 12 months post-auto-SCT is associated with superior overall and progression free survival in patients with MM. Efforts to better enhance polyclonal recovery deserve further investigation.

  19. Tattooing to "Toughen up": Tattoo experience and secretory immunoglobulin A.

    Science.gov (United States)

    Lynn, Christopher D; Dominguez, Johnna T; DeCaro, Jason A

    2016-09-10

    A costly signaling model suggests tattooing inoculates the immune system to heightened vigilance against stressors associated with soft tissue damage. We sought to investigate this "inoculation hypothesis" of tattooing as a costly honest signal of fitness. We hypothesized that the immune system habituates to the tattooing stressor in repeatedly tattooed individuals and that immune response to the stress of the tattooing process would correlate with lifetime tattoo experience. Participants were 24 women and 5 men (aged 18-47). We measured immune function using secretory immunoglobulin A (SIgA) and cortisol (sCORT) in saliva collected before and after tattoo sessions. We measured tattoo experience as a sum of number of tattoos, lifetime hours tattooed, years since first tattoo, percent of body covered, and number of tattoo sessions. We predicted an inverse relationship between SIgA and sCORT and less SIgA immunosuppression among those with more tattoo experience. We used hierarchical multiple regression to test for a main effect of tattoo experience on post-tattoo SIgA, controlling for pretest SIgA, tattoo session duration, body mass, and the interaction between tattoo experience and test session duration. The regression model was significant (P = 0.006) with a large effect size (r(2)  = 0.711) and significant and positive main (P = 0.03) and interaction effects (P = 0.014). Our data suggest that the body habituates over time to the tattooing stressor. It is possible that individuals with healthy immune systems heal faster, making them more likely to get multiple tattoos. Am. J. Hum. Biol. 28:603-609, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Exquisite response to intravenous immunoglobulin in Susac syndrome during pregnancy

    Directory of Open Access Journals (Sweden)

    Enrique Gomez-Figueroa

    2018-03-01

    Full Text Available Introduction: From its initial report on two female patients in 1979 by J.O. Susac, Susac syndrome (SuS or SICRET (small infarctions of cochlear, retinal and encephalic tissue has persisted as an elusive entity. To date the available evidence for its treatment is based on case reports and case series. The largest systematic review described only 304 reported cases since the 1970s. Here we presented the first reported case to our knowledge in Mexican population and the unusual presentation in a pregnant patient. Case presentation: A 34-year-old Hispanic woman was brought to the ER in our hospital for apathy and behavioral changes. Upon arrival at the ER, her husband described a one-month history of behavioral changes with apathy, progressive abulia, visuospatial disorientation, and gait deterioration. The initial lab test shows no significance except by a positive qualitative hCG. An MRI was obtained and showed hyperintense periventricular white matter lesions in T2 and FLAIR sequences also involving bilateral basal ganglia and with predominant affection of the corpus callosum, in addition to infratentorial cerebellar lesions. After treatment with intravenous immunoglobulins a marked and prompt clinical and radiological improvement was observed. Conclusion: SuS is still an elusive disease. To date, no definitive score or clinical feature can predict the outcome of the disease. The presentation during pregnancy is also rare and therefore the optimal treatment and the prognosis is unknown. We hope that this article will serve as a foundation for future research. Keywords: Susac syndrome, Neuroinflammation, Corpus callosum, Demyelinating disease, Vasculitis

  1. SCM, the M Protein of Streptococcus canis Binds Immunoglobulin G.

    Science.gov (United States)

    Bergmann, Simone; Eichhorn, Inga; Kohler, Thomas P; Hammerschmidt, Sven; Goldmann, Oliver; Rohde, Manfred; Fulde, Marcus

    2017-01-01

    The M protein of Streptococcus canis (SCM) is a virulence factor and serves as a surface-associated receptor with a particular affinity for mini-plasminogen, a cleavage product of the broad-spectrum serine protease plasmin. Here, we report that SCM has an additional high-affinity immunoglobulin G (IgG) binding activity. The ability of a particular S. canis isolate to bind to IgG significantly correlates with a scm -positive phenotype, suggesting a dominant role of SCM as an IgG receptor. Subsequent heterologous expression of SCM in non-IgG binding S. gordonii and Western Blot analysis with purified recombinant SCM proteins confirmed its IgG receptor function. As expected for a zoonotic agent, the SCM-IgG interaction is species-unspecific, with a particular affinity of SCM for IgGs derived from human, cats, dogs, horses, mice, and rabbits, but not from cows and goats. Similar to other streptococcal IgG-binding proteins, the interaction between SCM and IgG occurs via the conserved Fc domain and is, therefore, non-opsonic. Interestingly, the interaction between SCM and IgG-Fc on the bacterial surface specifically prevents opsonization by C1q, which might constitute another anti-phagocytic mechanism of SCM. Extensive binding analyses with a variety of different truncated SCM fragments defined a region of 52 amino acids located in the central part of the mature SCM protein which is important for IgG binding. This binding region is highly conserved among SCM proteins derived from different S. canis isolates but differs significantly from IgG-Fc receptors of S. pyogenes and S. dysgalactiae sub. equisimilis , respectively. In summary, we present an additional role of SCM in the pathogen-host interaction of S. canis . The detailed analysis of the SCM-IgG interaction should contribute to a better understanding of the complex roles of M proteins in streptococcal pathogenesis.

  2. Immunoglobulin gene usage in the human anti-pathogen response.

    Science.gov (United States)

    Newkirk, M M; Rioux, J D

    1995-09-01

    The human antibody response to foreign pathogens is generated to a relatively small number of target surface proteins and carbohydrates that nonetheless have an extensive array of epitopes. The study of human monoclonal antibodies to different pathogens shows that there are a diversity of mechanisms used to generate a sufficient repertoire of antibodies to combat the invading pathogens. Although many different immunoglobulin gene elements are used to construct the anti-pathogen response, some elements are used more often than would be expected if all elements were used randomly. For example, the immune response to Haemophilus influenzae polysaccharide appears to be quite narrow, being restricted primarily to a specific heavy-chain gene, 3-15, and a lambda light-chain family II member, 4A. In contrast, for the immune response to cytomegalovirus proteins, a wider group of gene elements is needed. It is also surprising that despite an investigator bias for IgG- rather than IgM-secreting immortal B cells (because of their high affinity and neutralizing abilities), 26% of light chains and 13% of heavy chains showed a very low level of somatic mutation, equivalent to an IgM molecule that has not undergone affinity maturation. Although some highly mutated IgG molecules are present in the anti-pathogen response, most of the monoclonal antibodies specific for viruses or bacteria have a level of somatic hypermutation similar to that of the adult IgM repertoire. A number of studies have shown that there are similarities in the antibody responses to pathogens and to self (autoantibodies).(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Predictors of nonresponse to intravenous immunoglobulin therapy in Kawasaki disease

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    Hyo Min Park

    2013-02-01

    Full Text Available &lt;b&gt;Purpose:&lt;/b&gt; It has been reported that 10% to 20% of children with Kawasaki disease (KD will not respond to intravenous immunoglobulin (IVIG treatment. In this study, we aimed to identify useful predictors of therapeutic failure in children with KD. &lt;b&gt;Methods:&lt;/b&gt; We examined 309 children diagnosed with KD at the Kyungpook National University Hospital and the Inje University Busan Paik Hospital between January 2005 and June 2011. We retrospectively reviewed their medical records and analyzed multiple parameters in responders and nonresponders to IVIG. &lt;b&gt;Results:&lt;/b&gt; Among the 309 children, 30 (9.7% did not respond to IVIG. They had significantly higher proportion of neutrophils, and higher levels of aspartate aminotransferase, alanine aminotransferase (ALT, total bilirubin, and N-terminal fragment of B-type natriuretic peptide than did responders. IVIGnonresponders had a significantly longer duration of hospitalization, and more frequently experienced coronary artery lesion, and sterile pyuria. No differences in the duration of fever at initial treatment or, clinical features were noted. &lt;b&gt;Conclusion:&lt;/b&gt; Two independent predictors (ALT?#248;4 IU/L, total bilirubin?#240;.9 mg/dL for nonresponse were confirmed through multivariate logistic regression analysis. Thus elevated ALT and total bilirubin levels might be useful in predicting nonresponse to IVIG therapy in children with KD.

  4. Immunoglobulin Genomics in the Guinea Pig (Cavia porcellus)

    Science.gov (United States)

    Guo, Yongchen; Bao, Yonghua; Meng, Qingwen; Hu, Xiaoxiang; Meng, Qingyong; Ren, Liming; Li, Ning; Zhao, Yaofeng

    2012-01-01

    In science, the guinea pig is known as one of the gold standards for modeling human disease. It is especially important as a molecular and cellular biology model for studying the human immune system, as its immunological genes are more similar to human genes than are those of mice. The utility of the guinea pig as a model organism can be further enhanced by further characterization of the genes encoding components of the immune system. Here, we report the genomic organization of the guinea pig immunoglobulin (Ig) heavy and light chain genes. The guinea pig IgH locus is located in genomic scaffolds 54 and 75, and spans approximately 6,480 kb. 507 VH segments (94 potentially functional genes and 413 pseudogenes), 41 DH segments, six JH segments, four constant region genes (μ, γ, ε, and α), and one reverse δ remnant fragment were identified within the two scaffolds. Many VH pseudogenes were found within the guinea pig, and likely constituted a potential donor pool for gene conversion during evolution. The Igκ locus mapped to a 4,029 kb region of scaffold 37 and 24 is composed of 349 Vκ (111 potentially functional genes and 238 pseudogenes), three Jκ and one Cκ genes. The Igλ locus spans 1,642 kb in scaffold 4 and consists of 142 Vλ (58 potentially functional genes and 84 pseudogenes) and 11 Jλ -Cλ clusters. Phylogenetic analysis suggested the guinea pig’s large germline VH gene segments appear to form limited gene families. Therefore, this species may generate antibody diversity via a gene conversion-like mechanism associated with its pseudogene reserves. PMID:22761756

  5. A phase 3 trial of IV immunoglobulin for Alzheimer disease.

    Science.gov (United States)

    Relkin, Norman R; Thomas, Ronald G; Rissman, Robert A; Brewer, James B; Rafii, Michael S; van Dyck, Christopher H; Jack, Clifford R; Sano, Mary; Knopman, David S; Raman, Rema; Szabo, Paul; Gelmont, David M; Fritsch, Sandor; Aisen, Paul S

    2017-05-02

    We tested biweekly infusions of IV immunoglobulin (IVIg) as a possible treatment for mild to moderate Alzheimer disease (AD) dementia. In a phase 3, double-blind, placebo-controlled trial, we randomly assigned 390 participants with mild to moderate AD to receive placebo (low-dose albumin) or IVIg (Gammagard Liquid; Baxalta, Bannockburn, IL) administered IV at doses of 0.2 or 0.4 g/kg every 2 weeks for 18 months. The primary cognitive outcome was change from baseline to 18 months on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale; the primary functional outcome was 18-month change on the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. Safety and tolerability data, as well as serial MRIs and plasma samples, were collected throughout the study from all enrolled participants. No beneficial effects were observed in the dual primary outcome measures for the 2 IVIg doses tested. Significant decreases in plasma Aβ42 (but not Aβ40) levels were observed in IVIg-treated participants. Analysis of safety data showed no difference between IVIg and placebo in terms of the rate of occurrence of amyloid-related imaging abnormalities (brain edema or microhemorrhage). IVIg-treated participants had more systemic reactions (chills, rashes) but fewer respiratory infections than participants receiving placebo. Participants with mild to moderate AD showed good tolerability of treatment with low-dose human IVIg for 18 months but did not show beneficial effects on cognition or function relative to participants who received placebo. NCT00818662. This study provides Class II evidence that IVIg infusions performed every 2 weeks do not improve cognition or function at 18 months in patients with mild to moderate AD. © 2017 American Academy of Neurology.

  6. The Unusual Genetics and Biochemistry of Bovine Immunoglobulins.

    Science.gov (United States)

    Stanfield, Robyn L; Haakenson, Jeremy; Deiss, Thaddeus C; Criscitiello, Michael F; Wilson, Ian A; Smider, Vaughn V

    2018-01-01

    Antibodies are the key circulating molecules that have evolved to fight infection by the adaptive immune system of vertebrates. Typical antibodies of most species contain six complementarity-determining regions (CDRs), where the third CDR of the heavy chain (CDR H3) has the greatest diversity and often makes the most significant contact with antigen. Generally, the process of V(D)J recombination produces a vast repertoire of antibodies; multiple V, D, and J gene segments recombine with additional junctional diversity at the V-D and D-J joints, and additional combinatorial possibilities occur through heavy- and light-chain pairing. Despite these processes, the overall structure of the resulting antibody is largely conserved, and binding to antigen occurs predominantly through the CDR loops of the immunoglobulin V domains. Bovines have deviated from this general paradigm by having few VH regions and thus little germline combinatorial diversity, but their antibodies contain long CDR H3 regions, with substantial diversity generated through somatic hypermutation. A subset of the repertoire comprises antibodies with ultralong CDR H3s, which can reach over 70 amino acids in length. Structurally, these unusual antibodies form a β-ribbon "stalk" and disulfide-bonded "knob" that protrude far from the antibody surface. These long CDR H3s allow cows to mount a particularly robust immune response when immunized with viral antigens, particularly to broadly neutralizing epitopes on a stabilized HIV gp140 trimer, which has been a challenge for other species. The unusual genetics and structural biology of cows provide for a unique paradigm for creation of immune diversity and could enable generation of antibodies against especially challenging targets and epitopes. © 2018 Elsevier Inc. All rights reserved.

  7. Increased Blood Levels of Growth Factors, Proinflammatory Cytokines, and Th17 Cytokines in Patients with Newly Diagnosed Type 1 Diabetes.

    Science.gov (United States)

    Alnek, Kristi; Kisand, Kalle; Heilman, Kaire; Peet, Aleksandr; Varik, Karin; Uibo, Raivo

    2015-01-01

    The production of several cytokines could be dysregulated in type 1 diabetes (T1D). In particular, the activation of T helper (Th) type 1 (Th1) cells has been proposed to underlie the autoimmune pathogenesis of the disease, although roles for inflammatory processes and the Th17 pathway have also been shown. Nevertheless, despite evidence for the role of cytokines before and at the onset of T1D, the corresponding findings are inconsistent across studies. Moreover, conflicting data exist regarding the blood cytokine levels in T1D patients. The current study was performed to investigate genetic and autoantibody markers in association with the peripheral blood cytokine profiles by xMap multiplex technology in newly diagnosed young T1D patients and age-matched healthy controls. The onset of young-age T1D was characterized by the upregulation of growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-7, the proinflammatory cytokine IL-1β (but not IL-6 or tumor necrosis factor [TNF]-α), Th17 cytokines, and the regulatory cytokines IL-10 and IL-27. Ketoacidosis and autoantibodies (anti-IA-2 and -ZnT8), but not human leukocyte antigen (HLA) genotype, influenced the blood cytokine levels. These findings broaden the current understanding of the dysregulation of systemic levels of several key cytokines at the young-age onset of T1D and provide a further basis for the development of novel immunoregulatory treatments in this disease.

  8. Modulation of cytokine and cytokine receptor/antagonist by treatment with doxycycline and tetracycline in patients with dengue fever.

    Science.gov (United States)

    Castro, J E Z; Vado-Solis, I; Perez-Osorio, C; Fredeking, T M

    2011-01-01

    Dengue virus infection can lead to dengue fever (DF) or dengue hemorrhagic fever (DHF). Disease severity has been linked to an increase in various cytokine levels. In this study, we evaluated the effectiveness of doxycycline and tetracycline to modulate serum levels of IL-6, IL-1B, and TNF and cytokine receptor/receptor antagonist TNF-R1 and IL-1RA in patients with DF or DHF. Hospitalized patients were randomized to receive standard supportive care or supportive care combined with doxycycline or tetracycline therapy. Serum cytokine and cytokine receptor/antagonist levels were determined at the onset of therapy and after 3 and 7 days. Cytokine and cytokine receptor/antagonist levels were substantially elevated at day 0. IL-6, IL-1β, and TNF remained at or above day 0 levels throughout the study period in untreated patients. Treatment with tetracycline or doxycycline resulted in a significant decline in cytokine levels. Similarly, IL-1RA and TNF-R1 serum concentrations were elevated at baseline and showed a moderate increase among untreated patients. Both drugs resulted in a significant rise in IL-1Ra levels by day 3 in patients. In contrast, treatment did not affect a similar result for TNF-R1. When compared to the control group, however, a significant rise post-treatment was seen upon intragroup analysis. Further analysis demonstrated that doxycycline was significantly more effective at modulating cytokine and cytokine receptor/antagonist levels than tetracycline.

  9. Cross-regulation of cytokine signalling: pro-inflammatory cytokines restrict IL-6 signalling through receptor internalisation and degradation.

    Science.gov (United States)

    Radtke, Simone; Wüller, Stefan; Yang, Xiang-ping; Lippok, Barbara E; Mütze, Barbara; Mais, Christine; de Leur, Hildegard Schmitz-Van; Bode, Johannes G; Gaestel, Matthias; Heinrich, Peter C; Behrmann, Iris; Schaper, Fred; Hermanns, Heike M

    2010-03-15

    The inflammatory response involves a complex interplay of different cytokines which act in an auto- or paracrine manner to induce the so-called acute phase response. Cytokines are known to crosstalk on multiple levels, for instance by regulating the mRNA stability of targeted cytokines through activation of the p38-MAPK pathway. In our study we discovered a new mechanism that answers the long-standing question how pro-inflammatory cytokines and environmental stress restrict immediate signalling of interleukin (IL)-6-type cytokines. We show that p38, activated by IL-1beta, TNFalpha or environmental stress, impairs IL-6-induced JAK/STAT signalling through phosphorylation of the common cytokine receptor subunit gp130 and its subsequent internalisation and degradation. We identify MK2 as the kinase that phosphorylates serine 782 in the cytoplasmic part of gp130. Consequently, inhibition of p38 or MK2, deletion of MK2 or mutation of crucial amino acids within the MK2 target site or the di-leucine internalisation motif blocks receptor depletion and restores IL-6-dependent STAT activation as well as gene induction. Hence, a novel negative crosstalk mechanism for cytokine signalling is described, where cytokine receptor turnover is regulated in trans by pro-inflammatory cytokines and stress stimuli to coordinate the inflammatory response.

  10. Elevated specific peripheral cytokines found in major depressive disorder patients with childhood trauma exposure: a cytokine antibody array analysis.

    Science.gov (United States)

    Lu, Shaojia; Peng, Hongjun; Wang, Lifeng; Vasish, Seewoobudul; Zhang, Yan; Gao, Weijia; Wu, Weiwei; Liao, Mei; Wang, Mi; Tang, Hao; Li, Wenping; Li, Weihui; Li, Zexuan; Zhou, Jiansong; Zhang, Zhijun; Li, Lingjiang

    2013-10-01

    Taking into consideration the previous evidence of revealing the relationship of early life adversity, major depressive disorder (MDD), and stress-linked immunological changes, we recruited 22 MDD patients with childhood trauma exposures (CTE), 21 MDD patients without CTE, and 22 healthy controls without CTE, and then utilized a novel cytokine antibody array methodology to detect potential biomarkers underlying MDD in 120 peripheral cytokines and to evaluate the effect of CTE on cytokine changes in MDD patients. Although 13 cytokines were identified with highly significant differences in expressions between MDD patients and normal controls, this relationship was significantly attenuated and no longer significant after consideration of the effect of CTE in MDD patients. Depressed individuals with CTE (TD patients) were more likely to have higher peripheral levels of those cytokines. Severity of depression was associated with plasma levels of certain increased cytokines; meanwhile, the increased cytokines led to a proper separation of TD patients from normal controls during clustering analyses. Our research outcomes add great strength to the relationship between depression and cytokine changes and suggest that childhood trauma may play a vital role in the co-appearance of cytokine changes and depression. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Intravenous immunoglobulin to treat hyperbilirubinemia in neonates with isolated Glucose-6-Phosphate dehydrogenase deficiency

    Directory of Open Access Journals (Sweden)

    Wadah Khriesat

    2017-04-01

    Full Text Available Background Glucose-6-phosphate dehydrogenase deficiency alone or concomitant with ABO isoimmunisation is a widespread indication for neonatal exchange transfusion. Aims To evaluate the effectiveness of Intravenous Immunoglobulin in the treatment of neonatal hyperbilirubinemia due to glucose-6-phosphate dehydrogenase deficiency. Methods A retrospective cohort study was conducted between 2006 and 2014 at the Jordan University of Science and technology. The medical records of 43 infants admitted to the neonatal intensive care unit for isolated glucose-6- phosphate dehydrogenase deficiency hemolytic disease of the newborns were reviewed. Patients were divided into two groups. Group I, a historical cohort, included newborns born between 2006 and 2010, Treatment included phototherapy and exchange transfusion. Group II included newborns born between 2011 and 2014, where, in addition to phototherapy, intravenous immunoglobulin was administered. The duration of phototherapy and number of exchange transfusions were evaluated. Results Of 412 newborns that were admitted with neonatal hyperbilirubinemia, Glucose-6-phosphate dehydrogenase deficiency was present in 43. Of these, 22, did not receive intravenous immunoglobulin and served as a control group. The other 21 newborns received intravenous immunoglobulin. There was no difference in the demographic characteristics between the two groups. Infants in the control group were significantly more likely to receive exchange blood transfusion than infants in the immunoglobulin treatment group, but were significantly less likely to need phototherapy. Conclusion Intravenous immunoglobulin is an effective alternative to exchange transfusion in infants with glucose-6-phosphate dehydrogenase deficiency hemolytic disease of the newborn. It is suggested that intravenous immunoglobulin may be beneficial as a prophylaxis for infants with hyperbilirubinemia.

  12. Withaferin A Associated Differential Regulation of Inflammatory Cytokines

    Directory of Open Access Journals (Sweden)

    Seema Dubey

    2018-02-01

    Full Text Available A role of inflammation-associated cytokines/chemokines has been implicated in a wide variety of human diseases. Here, we investigated the regulation of inflammatory cytokines released by monocyte-derived THP-1 cells following treatment with the dietary agent withaferin A (WFA. Membrane-based cytokine array profiling of the culture supernatant from adenosine triphosphate-stimulated WFA-treated THP-1 cells showed differential regulation of multiple cytokines/chemokines. A selected group of cytokines/chemokines [interleukin-1 beta (IL-1β, CCL2/MCP-1, granulocyte-macrophage colony stimulating factor, PDGF-AA, PTX3, cystatin-3, relaxin-2, TNFRSF8/CD30, and ACRP30] was validated at the transcription level using qPCR. In silico analysis for transcriptional binding factors revealed the presence of nuclear factor-kappa B (NF-κB in a group of downregulated cytokine gene promoters. WFA treatment of THP-1 cells blocks the nuclear translocation of NF-kB and corresponds with the reduced levels of cytokine secretion. To further understand the differential expression of cytokines/chemokines, we showed that WFA alters the nigericin-induced co-localization of NLRP3 and ASC proteins, thereby inhibiting caspase-1 activation, which is responsible for the cleavage and maturation of pro-inflammatory cytokines IL-1β and IL-18. These data suggest that dietary agent WFA concurrently targets NF-κB and the inflammasome complex, leading to inhibition of IL-1β and IL-18, respectively, in addition to differential expression of multiple cytokines/chemokines. Taken together, these results provide a rationale for using WFA to further explore the anti-inflammatory mechanism of cytokines/chemokines associated with inflammatory diseases.

  13. A preliminary randomized double blind placebo-controlled trial of intravenous immunoglobulin for Japanese encephalitis in Nepal.

    Directory of Open Access Journals (Sweden)

    Ajit Rayamajhi

    Full Text Available Japanese encephalitis (JE virus (JEV is a mosquito-borne flavivirus found across Asia that is closely related to West Nile virus. There is no known antiviral treatment for any flavivirus. Results from in vitro studies and animal models suggest intravenous immunoglobulin (IVIG containing virus-specific neutralizing antibody may be effective in improving outcome in viral encephalitis. IVIG's anti-inflammatory properties may also be beneficial.We performed a pilot feasibility randomized double-blind placebo-controlled trial of IVIG containing anti-JEV neutralizing antibody (ImmunoRel, 400mg/kg/day for 5 days in children with suspected JE at two sites in Nepal; we also examined the effect on serum neutralizing antibody titre and cytokine profiles. 22 children were recruited, 13 of whom had confirmed JE; 11 received IVIG and 11 placebo, with no protocol violations. One child (IVIG group died during treatment and two (placebo subsequently following hospital discharge. Overall, there was no difference in outcome between treatment groups at discharge or follow up. Passive transfer of anti-JEV antibody was seen in JEV negative children. JEV positive children treated with IVIG had JEV-specific neutralizing antibody titres approximately 16 times higher than those treated with placebo (p=0.2, which was more than could be explained by passive transfer alone. IL-4 and IL-6 were higher in the IVIG group.A trial of IVIG for JE in Nepal is feasible. IVIG may augment the development of neutralizing antibodies in JEV positive patients. IVIG appears an appealing option for JE treatment that warrants further study.ClinicalTrials.gov NCT01856205.

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

    Directory of Open Access Journals (Sweden)

    Enas A. S. Attia

    2010-01-01

    Full Text Available 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' HLA-DRB1 typing by sequence specific oligonucleotide probe technique was compared to normal Egyptian population. We found significantly elevated serum IL-4 and total IgE in AA patients (particularly alopecia universalis, AU, and chronic patients (P<.01. HLA-DRB1*11 is a general susceptibility/chronicity allele. DRB1*13 is a protective allele. DRB1*01 and DRB1*07 are linked to chronicity. Localized AA showed decreased DRB1*03 and DRB1*07. Extensive forms showed increased DRB1*08 and decreased DRB1*04. Elevated IL4 and IgE were observed in patients with DRB1*07 and DRB1*11 not DRB1*04. Conclusion. Serum IL-4 and IgE are elevated in nonatopic AA patients, particularly AU and chronic disease. Relevant susceptibility, chronicity, and severity HLADRB1 alleles may have a role in determining type, magnitude, and duration of immune response in AA favouring increased IL4 and IgE.

  15. Leukocyte-associated immunoglobulin-like receptor-1 is expressed on human megakaryocytes and negatively regulates the maturation of primary megakaryocytic progenitors and cell line

    International Nuclear Information System (INIS)

    Xue, Jiangnan; Zhang, Xiaoshu; Zhao, Haiya; Fu, Qiang; Cao, Yanning; Wang, Yuesi; Feng, Xiaoying; Fu, Aili

    2011-01-01

    Research highlights: → LAIR-1 is expressed on human megakaryocytes from an early stage. → Up-regulation of LAIR-1 negatively regulates megakaryocytic differentiation of cell line. → LAIR-1 negatively regulates the differentiation of primary megakaryocytic progenitors. -- Abstract: Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an inhibitory collagen receptor which belongs to the immunoglobulin (Ig) superfamily. Although the inhibitory function of LAIR-1 has been extensively described in multiple leukocytes, its role in megakaryocyte (MK) has not been explored so far. Here, we show that LAIR-1 is expressed on human bone marrow CD34 + CD41a + and CD41a + CD42b + cells. LAIR-1 is also detectable in a fraction of human cord blood CD34 + cell-derived MK that has morphological characteristics of immature MK. In megakaryoblastic cell line Dami, the membrane protein expression of LAIR-1 is up-regulated significantly when cells are treated with phorbol ester phorbol 12-myristate 13-acetate (PMA). Furthermore, cross-linking of LAIR-1 in Dami cells with its natural ligand or anti-LAIR-1 antibody leads to the inhibition of cell proliferation and PMA-promoted differentiation when examined by the MK lineage-specific markers (CD41a and CD42b) and polyploidization. In addition, we also observed that cross-linking of LAIR-1 results in decreased MK generation from primary human CD34 + cells cultured in a cytokines cocktail that contains TPO. These results suggest that LAIR-1 is a likely candidate for an early marker of MK differentiation, and provide initial evidence indicating that LAIR-1 serves as a negative regulator of megakaryocytopoiesis.

  16. Plasticity of regulatory T cells under cytokine pressure.

    Science.gov (United States)

    Diaconu, Carmen C; Neagu, Ana I; Lungu, Răzvan; Tardei, Graţiela; Alexiu, Irina; Bleotu, Coralia; Economescu, Mihaela Chivu; Bumbăcea, Roxana S; Pele, Irina; Bumbăcea, Dragoş

    2010-01-01

    CD4+ T helper (Th) cells have been divided into different subsets as defined by their cytokine products and functions after their activation. CD4+ T cell subsets are continuously discovered and until now Th1, Th2, Th9, Th17, and regulatory T (Treg) cells have been almost unanimously recognized but yet not completely characterized. The selective production of cytokines by each of the subsets is probably the master key of the mechanisms of immune regulation. The cytokine milieu is extremely important on deciding the fate of T cells. Generally, more than one cytokine is needed for differentiating to a particular lineage and just recently it was shown that this status quo of commitment could be challenged. It is well known that cytokines bind to Type I/II cytokine receptors signaling via Janus kinases (JAKs) followed by activation of Signal Transducer and Activator of Transcription (STAT). STAT molecules work together with other transcription factors (Foxp3, RORgammat and RORalpha, T-bet, GATA3, Runx 1, NFAT, etc.) also controlled by cytokines, in modulating the Th phenotype and functions. In this review, we analyze the plasticity of Treg population focusing on the most recent discoveries on how microenvironmental cytokines refine/modify Treg phenotype and function, thus changing their fate.

  17. Modulation of cytokine production profiles in splenic dendritic cells ...

    African Journals Online (AJOL)

    We examined the role of splenic dendritic cells in immune response to Toxoplasma gondii infection in SAG1 (P30+) transgenic mice by investigating the kinetics of intracellular cytokines expression of IL-4, IL-10, IL-12 and IFN-γ by intracellular cytokine staining (ICS) using flow cytometry, and compared the results to those of ...

  18. Cytokines: abnormalities in major depression and implications for pharmacological treatment.

    LENUS (Irish Health Repository)

    O'Brien, Sinead M

    2012-02-03

    The role of cytokines in depression was first considered when the cytokine interferon resulted in "sickness behaviour", the symptoms of which are similar to those of major depression. The latter is associated with an increase in pro-inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha). These cytokines are potent modulators of corticotropin-releasing hormone (CRH) which produces heightened hypothalamic-pituitary-adrenal axis (HPA) activity characterized by increases in ACTH and cortisol, both of which are reported elevated in major depression. Antidepressant treatment has immunomodulatory effects with increases in the production of IL-10, which is an anti-inflammatory cytokine. This review based on a Medline search from 1980-2003, focuses on the evidence available of cytokine changes in acute stress, chronic stress and major depression. It examines the effects of antidepressant treatment on immune parameters in both animal models and clinical trials. We suggest that future antidepressants may target the immune system by either blocking the actions of pro-inflammatory cytokines or increasing the production of anti-inflammatory cytokines.

  19. Peripheral parasitaemia and its association with plasma cytokines ...

    African Journals Online (AJOL)

    Also, plasma levels of cytokines were measured using Th1/Th2 human cytokine ELISA kits (Abcam, UK). Analysis of Variance and Student's t-test were used for Comparison of groups while Pearson's Correlation Coefficient was used for tests of association. Results: The results revealed a mean parasite density of ...

  20. Anti-cytokine therapies in T1D

    DEFF Research Database (Denmark)

    Nepom, Gerald T; Ehlers, Mario; Mandrup-Poulsen, Thomas

    2013-01-01

    Therapeutic targeting of proinflammatory cytokines is clinically beneficial in several autoimmune disorders. Several of these cytokines are directly implicated in the pathogenesis of type 1 diabetes, suggesting opportunities for design of clinical trials in type 1 diabetes that incorporate select...... suitable for modulating the immune response in T1D....

  1. Cytokines and chemokines involved in acute retinal necrosis

    NARCIS (Netherlands)

    L. De Visser (Lenneke); J.H. de Boer (Joke); G.T. Rijkers; Wiertz, K. (Karin); H.J. van den Ham; de Boer, R. (Rob); van Loon, A.M. (Anton M.); A. Rothová (Aniki); J.D.F. de Groot-Mijnes (Jolanda )

    2017-01-01

    textabstractPURPOSE. To investigate which cytokines and chemokines are involved in the immunopatho-genesis of acute retinal necrosis (ARN), and whether cytokine profiles are associated with clinical manifestations, such as visual outcome. METHODS. Serum and aqueous humor (AH) samples of 19 patients

  2. Demystifying the cytokine network: Mathematical models point the way.

    Science.gov (United States)

    Morel, Penelope A; Lee, Robin E C; Faeder, James R

    2017-10-01

    Cytokines provide the means by which immune cells communicate with each other and with parenchymal cells. There are over one hundred cytokines and many exist in families that share receptor components and signal transduction pathways, creating complex networks. Reductionist approaches to understanding the role of specific cytokines, through the use of gene-targeted mice, have revealed further complexity in the form of redundancy and pleiotropy in cytokine function. Creating an understanding of the complex interactions between cytokines and their target cells is challenging experimentally. Mathematical and computational modeling provides a robust set of tools by which complex interactions between cytokines can be studied and analyzed, in the process creating novel insights that can be further tested experimentally. This review will discuss and provide examples of the different modeling approaches that have been used to increase our understanding of cytokine networks. This includes discussion of knowledge-based and data-driven modeling approaches and the recent advance in single-cell analysis. The use of modeling to optimize cytokine-based therapies will also be discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Serum triiodothyronine levels and inflammatory cytokine production capacity

    NARCIS (Netherlands)

    Rozing, Maarten P.; Westendorp, Rudi G J; Maier, Andrea B.; Wijsman, Carolien A.; Frölich, Marijke; De Craen, Anton J M; Van Heemst, Diana

    Increasing evidence suggests that pro-inflammatory cytokines are at play in lowering peripheral thyroid hormone levels during critical illness. Conversely, thyroid hormones have been suggested to enhance production of inflammatory cytokines. In view of these considerations, we hypothesized a mutual

  4. Inflammatory cytokines and risk of coronary heart disease

    DEFF Research Database (Denmark)

    Kaptoge, Stephen; Seshasai, Sreenivasa Rao Kondapally; Gao, Pei

    2014-01-01

    Because low-grade inflammation may play a role in the pathogenesis of coronary heart disease (CHD), and pro-inflammatory cytokines govern inflammatory cascades, this study aimed to assess the associations of several pro-inflammatory cytokines and CHD risk in a new prospective study, including meta...

  5. Cytokines and Chemokines Involved in Acute Retinal Necrosis

    NARCIS (Netherlands)

    de Visser, Lenneke; H de Boer, Joke; T Rijkers, Ger; Wiertz, Karin; van den Ham, Henk-Jan; de Boer, Rob; M van Loon, Anton; Rothova, Aniki; de Groot-Mijnes, Jolanda D F

    2017-01-01

    Purpose: To investigate which cytokines and chemokines are involved in the immunopathogenesis of acute retinal necrosis (ARN), and whether cytokine profiles are associated with clinical manifestations, such as visual outcome. Methods: Serum and aqueous humor (AH) samples of 19 patients with ARN were

  6. Cytokines and the neurodevelopmental basis of mental illness

    Directory of Open Access Journals (Sweden)

    Udani eRatnayake

    2013-10-01

    Full Text Available Epidemiological studies suggest that prenatal exposure to different types of viral or bacterial infections may be associated with similar outcomes; i.e., an increased risk of mental illness disorders in the offspring. Infections arising from various causes have similar debilitating effects in later life, suggesting that the exact pathogen may not be the critical factor in determining the neurological and cognitive outcome in the offspring. Instead, it is thought that response of the innate immune system, specifically the increased production of inflammatory cytokines, may be the critical mediator in altering fetal brain development pre-disposing the offspring to mental illness disorders later in life. Inflammatory cytokines are essential for normal brain development. Factors such as the site of cytokine production, a change in balance between anti- and pro- inflammatory cytokines, placental transfer of cytokines, the effects of cytokines on glial cells, and the effects of glucocorticoids are important when evaluating the impact of maternal infection on fetal brain development. Although it is clear that cytokines are altered in the fetal brain following maternal infection, further evidence is required to determine if cytokines are the critical factor that alters the trajectory of brain development, subsequently leading to postnatal behavioural and neurological abnormalities.

  7. Biologics for Targeting Inflammatory Cytokines, Clinical Uses, and Limitations

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    Peleg Rider

    2016-01-01

    Full Text Available Proinflammatory cytokines are potent mediators of numerous biological processes and are tightly regulated in the body. Chronic uncontrolled levels of such cytokines can initiate and derive many pathologies, including incidences of autoimmunity and cancer. Therefore, therapies that regulate the activity of inflammatory cytokines, either by supplementation of anti-inflammatory recombinant cytokines or by neutralizing them by using blocking antibodies, have been extensively used over the past decades. Over the past few years, new innovative biological agents for blocking and regulating cytokine activities have emerged. Here, we review some of the most recent approaches of cytokine targeting, focusing on anti-TNF antibodies or recombinant TNF decoy receptor, recombinant IL-1 receptor antagonist (IL-1Ra and anti-IL-1 antibodies, anti-IL-6 receptor antibodies, and TH17 targeting antibodies. We discuss their effects as biologic drugs, as evaluated in numerous clinical trials, and highlight their therapeutic potential as well as emphasize their inherent limitations and clinical risks. We suggest that while systemic blocking of proinflammatory cytokines using biological agents can ameliorate disease pathogenesis and progression, it may also abrogate the hosts defense against infections. Moreover, we outline the rational need to develop new therapies, which block inflammatory cytokines only at sites of inflammation, while enabling their function systemically.

  8. Live, Attenuated Influenza A H5N1 Candidate Vaccines Provide Broad Cross-Protection in Mice and Ferrets

    Science.gov (United States)

    Mills, Kimberly L; Jin, Hong; Duke, Greg; Lu, Bin; Luke, Catherine J; Murphy, Brian; Swayne, David E; Kemble, George; Subbarao, Kanta

    2006-01-01

    Background Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic. Methods and Findings Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA) and a wild-type (wt) N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted (ca) influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2), were generated by reverse genetics. The H5N1 ca vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the ca vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 106 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous wt H5N1 viruses from different genetic sublineages (clades 1, 2, and 3) that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous wt H5N1 viruses. Conclusions The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 ca vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans. PMID:16968127

  9. Live, attenuated influenza A H5N1 candidate vaccines provide broad cross-protection in mice and ferrets.

    Directory of Open Access Journals (Sweden)

    Amorsolo L Suguitan

    2006-09-01

    Full Text Available Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic.Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA and a wild-type (wt N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted (ca influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2, were generated by reverse genetics. The H5N1 ca vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the ca vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 10(6 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous wt H5N1 viruses from different genetic sublineages (clades 1, 2, and 3 that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous wt H5N1 viruses.The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 ca vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans.

  10. Debris flows on forested cones – reconstruction and comparison of frequencies in two catchments in Val Ferret, Switzerland

    Directory of Open Access Journals (Sweden)

    M. Bollschweiler

    2007-01-01

    Full Text Available Debris flows represent a major threat to infrastructure in many regions of the Alps. Since systematic acquisition of data on debris-flow events in Switzerland only started after the events of 1987, there is a lack of historical knowledge on earlier debris-flow events for most torrents. It is therefore the aim of this study to reconstruct the debris-flow activity for the Reuse de Saleinaz and the La Fouly torrents in Val Ferret (Valais, Switzerland. In total, 556 increment cores from 278 heavily affected Larix decidua Mill., Picea abies (L. Karst. and Pinus sylvestris L. trees were sampled. Trees on the cone of Reuse de Saleinaz show an average age of 123 years at sampling height, with the oldest tree aged 325 years. Two periods of intense colonization (the 1850s–1880s and the 1930s–1950s are observed, probably following high-magnitude events that would have eliminated the former forest stand. Trees on the cone of Torrent de la Fouly indicate an average age of 119 years. As a whole, tree-ring analyses allowed assessment of 333 growth disturbances belonging to 69 debris-flow events. While the frequency for the Reuse de Saleinaz study site comprises 39 events between AD 1743 and 2003, 30 events could be reconstructed at the Torrent de la Fouly for the period 1862–2003. Even though the two study sites evince considerably different characteristics in geology, debris-flow material and catchment morphology, they apparently produce debris flows at similar recurrence intervals. We suppose that, in the study region, the triggering and occurrence of events is transport-limited rather than weathering-limited.

  11. Centrally located GLP-1 receptors modulate gastric slow waves and cardiovascular function in ferrets consistent with the induction of nausea.

    Science.gov (United States)

    Lu, Zengbing; Yeung, Chi-Kong; Lin, Ge; Yew, David T W; Andrews, P L R; Rudd, John A

    2017-10-01

    Glucagon-like peptide-1 (GLP-1) receptor agonists are indicated for the treatment of Type 2 diabetes and obesity, but can cause nausea and emesis in some patients. GLP-1 receptors are distributed widely in the brain, where they contribute to mechanisms of emesis, reduced appetite and aversion, but it is not known if these centrally located receptors also contribute to a modulation of gastric slow wave activity, which is linked causally to nausea. Our aim was to investigate the potential of the GLP-1 receptor agonist, exendin-4, administered into the 3rd ventricle to modulate emesis, feeding and gastric slow wave activity. Thermoregulation and cardiovascular parameters were also monitored, as they are disturbed during nausea. Ferrets were used as common laboratory rodents do not have an emetic reflex. A guide cannula was implanted into the 3rd ventricle for delivering a previously established dose of exendin-4 (10nmol), which had been shown to induce emesis and behaviours indicative of 'nausea'. Radiotelemetry recorded gastric myoelectric activity (GMA; slow waves), blood pressure and heart rate variability (HRV), and core temperature; food intake and behaviour were also assessed. Exendin-4 (10nmol, i.c.v.) decreased the dominant frequency of GMA, with an associated increase in the percentage of bradygastric power (lasting ~4h). Food intake was inhibited in all animals, with 63% exhibiting emesis. Exendin-4 also increased blood pressure (lasting ~24h) and heart rate (lasting ~7h), decreased HRV (lasting ~24h), and caused transient hyperthermia. None of the above parameters were emesis-dependent. The present study shows for the first time that gastric slow waves may be modulated by GLP-1 receptors in the brain through mechanisms that appear independent from emesis. Taken together with a reduction in HRV, the findings are consistent with changes associated with the occurrence of nausea in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Permeability of ferret trachea in vitro to 99m Tc-DTPA and [14C]antipyrine

    International Nuclear Information System (INIS)

    Hanafi, Z.; Webber, S.E.; Widdicombe, J.G.

    1994-01-01

    Platelet-activating factor (PAF) and vasoactive drugs were tested on permeability of ferret trachea in vitro by measuring fluxes of 99m T c -diethylenetriamine pentaacetic acid ( 99m T c -DTPA; hydrophilic) and [ 14 C]antipyrine ([ 14 C]AP; lipophilic) across the tracheal wall. Tracheae were bathed on both sides with Krebs-Henseleit buffer, with luminal buffer containing either 99m T c -DTPA or [ 14 C]AP. Luminal and abluminal radioactivities, potential difference, and tracheal smooth muscle tone were measured. Baseline 99m T c -DTPA and [ 14 C]AP permeability coefficients were - 4.7 ± 0.6 (SE) x 10 -7 and -2.2 ± 0.1 x 10 -5 cm/s, respectively. PAF (10 μM) increased permeability to 99m T c -DTPA to -35.3 ± 7.6 x 10 -7 cm/s (P 14 C]AP did not change, suggesting that paracellular but not transcellular transport was affected. Abluminal and luminal applications of methacholine (MCh, 20 μM), phenylephrine (PE, 100 μM), and albuterol (Alb, 100 μM) caused no change in permeability to 99m T c -DTPA before or after exposure to luminal PAF, but abluminal histamine (Hist, 10 μM) significantly increased permeability. Abluminal Hist decreased permeability to [ 14 C]AP before and after exposure to PAF. MCh, PE, and Hist increased smooth muscle tone; Alb and PAF had no effect. Thus, only PAF and Hist altered permeability to 99m T c -DTPA, and MCh, PE, and Hist changed smooth muscle tone. Tracheal permeability changes were greater for the hydrophilic than for the lipophilic agent. 37 refs., 11 figs., 1 tab

  13. Cytokine modulation by glucocorticoids: mechanisms and actions in cellular studies.

    Science.gov (United States)

    Brattsand, R; Linden, M

    1996-01-01

    Glucocorticoids inhibit the expression and action of most cytokines. This is part of the in vivo feed-back system between inflammation-derived cytokines and CNS-adrenal produced corticosteroids with the probable physiological relevance to balance parts of the host defence and anti-inflammatory systems of the body. Glucocorticoids modulate cytokine expression by a combination of genomic mechanisms. The activated glucocorticoid-receptor complex can (i) bind to and inactivate key proinflammatory transcription factors (e.g. AP-1, NF kappa B). This takes place at the promotor responsive elements of these factors, but has also been reported without the presence of DNA; (ii) via glucocorticoid responsive elements (GRE), upregulate the expression of cytokine inhibitory proteins, e.g. I kappa B, which inactivates the transcription factor NF kappa B and thereby the secondary expression of a series of cytokines; (iii) reduce the half-life time and utility of cytokine mRNAs. In studies with triggered human blood mononuclear cells in culture, glucocorticoids strongly diminish the production of the 'initial phase' cytokines IL-1 beta and TNF-alpha and the 'immunomodulatory' cytokines IL-2, IL-3, IL-4, IL-5, IL-10, IL-12 and IFN-gamma, as well as of IL-6, IL-8 and the growth factor GM-CSF. While steroid treatment broadly attenuates cytokine production, it cannot modulate it selectively, e.g. just the TH0, the TH1 or the TH2 pathways. The production of the 'anti-inflammatory' IL-10 is also inhibited. The exceptions of steroid down-regulatory activity on cytokine expression seem to affect 'repair phase' cytokines like TGF-beta and PDGF. These are even reported to be upregulated, which may explain the rather weak steroid dampening action on healing and fibrotic processes. Some growth factors, e.g. G-CSF and M-CSF, are only weakly affected. In addition to diminishing the production of a cytokine, steroids can also often inhibit its subsequent actions. Because cytokines work in

  14. Role of IL-38 and Its Related Cytokines in Inflammation

    Directory of Open Access Journals (Sweden)

    Xianli Yuan

    2015-01-01

    Full Text Available Interleukin- (IL- 38 is a recently discovered cytokine and is the tenth member of the IL-1 cytokine family. IL-38 shares structural features with IL-1 receptor antagonist (IL-1Ra and IL-36Ra. IL-36R is the specific receptor of IL-38, a partial receptor antagonist of IL-36. IL-38 inhibits the production of T-cell cytokines IL-17 and IL-22. IL-38 also inhibits the production of IL-8 induced by IL-36γ, thus inhibiting inflammatory responses. IL-38-related cytokines, including IL-1Ra and IL-36Ra, are involved in the regulation of inflammation and immune responses. The study of IL-38 and IL-38-related cytokines might provide new insights for developing anti-inflammatory treatments in the near future.

  15. The inflammatory cytokines: molecular biomarkers for major depressive disorder?

    Science.gov (United States)

    Martin, Charlotte; Tansey, Katherine E; Schalkwyk, Leonard C; Powell, Timothy R

    2015-01-01

    Cytokines are pleotropic cell signaling proteins that, in addition to their role as inflammatory mediators, also affect neurotransmitter systems, brain functionality and mood. Here we explore the potential utility of cytokine biomarkers for major depressive disorder. Specifically, we explore how genetic, transcriptomic and proteomic information relating to the cytokines might act as biomarkers, aiding clinical diagnosis and treatment selection processes. We advise future studies to investigate whether cytokine biomarkers might differentiate major depressive disorder patients from other patient groups with overlapping clinical characteristics. Furthermore, we invite future pharmacogenetic studies to investigate whether early antidepressant-induced changes to cytokine mRNA or protein levels precede behavioral changes and act as longer-term predictors of clinical antidepressant response.

  16. METHODOLOGICAL APPROACHES TO EXPERT EVALUATION OF PRECLINICAL AND CLINICAL TRIALS OF HUMAN IMMUNOGLOBULIN PRODUCTS

    Directory of Open Access Journals (Sweden)

    V. B. Ivanov

    2017-01-01

    Full Text Available The article considers the experience of Russian and leading foreign regulatory agencies in organisation and conduction of preclinical and clinical trials of human immunoglobulin products. The authors suggest a classification of human immunoglobulins and provide updated information on authorization of these products in Russia. The article summarizes methodological approaches, basic scientific principles and criteria relating to expert evaluation of preclinical and clinical trials of blood products. The authors further define the expert body’s requirements for data on preclinical and clinical trials of human normal immuniglobulins and human specific immunoglobulins for the prevention and/or treatment of infectious and non-infectious diseases which are submitted as part of applications for marketing authorization or marketing authorization variation. The article suggests programs of preclinical and clinical trials for human normal immunoglobulins and human specific immunoglobulins for the prevention and/or treatment of infectious and non-infectious diseases that are aligned with the Russian legislation and Eurasian Economic Union’s regulations on medicines circulation, and have been elaborated with respect to the guidelines of the European Medicines Agency.

  17. Citoquinas en tuberculosis Cytokines in tuberculosis

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    Jaime I. Rodríguez

    1997-04-01

    Full Text Available La tuberculosis continúa siendo un modelo inmunológico para estudiar las infecciones intracelulares. Entenderlos complejos mecanismos de interacción de la micobacteria con el sistema inmune del hospedero permitirá un manejo más racional de los fenómenos clínicos que se presentan en la enfermedad. Las citoquinas desempeñan un papel fundamental tanto en el desarrollo de los mecanismos de inmunidad protectora como en el daño tisular presente en esta enfermedad. La estimulación in vitro de linfocitos de sujetos sanos tuberculino positivos con antígenos específicos induce preferencial mente un patrón de citoquinas tipo I (1'IL-2, 1'IFN-y, ~IL-4, ~IL-5, mientras que en la mayoría de los pacientes no se presenta este patrón. Las citoquinas tipo I conducen a la activación de los macrófagos que a su vez inhiben la replicación de las micobacterias. En el ratón, los macrófagos activados inhiben la micobacteria por medio del óxido nítrico; en los humanos la producción de óxido nítrico por los macrófagos no está plenamente demostrada. Recientemente se ha demostrado que la infección con M. tuberculosis puede inducir apoptosis en los macrófagos infectados. La apoptosis depende de la producción del Factor de Necrosis Tumoral a y de óxido nítrico. Paradójicamente, ellipoarabinomanán manosilado (ManLAM presente en la pared de las micobacterias inhibe la apoptosis. Estos hallazgos muestran un nuevo fenómeno en la interacción micobacteriamacrófago el cual debe estar finamente regulado tanto en el microorganismo como en el hospedero. Tuberculosis continues to be a model to study the immunological aspects of intracellular infections. A better understanding of the mycobacteria.host interaction would allow a more rational approach to the clinical problems of this disease. Cytokines playa key role in the development of protective immunity as well as in the tissue injury that occurs during the disease. In vitro stimulation with

  18. A single base-pair change in 2009 H1N1 hemagglutinin increases human receptor affinity and leads to efficient airborne viral transmission in ferrets.

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    Akila Jayaraman

    2011-03-01

    Full Text Available The 2009 H1N1 influenza A virus continues to circulate among the human population as the predominant H1N1 subtype. Epidemiological studies and airborne transmission studies using the ferret model have shown that the transmission efficiency of 2009 H1N1 viruses is lower than that of previous seasonal strains and the 1918 pandemic H1N1 strain. We recently correlated this reduced transmission efficiency to the lower binding affinity of the 2009 H1N1 hemagglutinin (HA to α2→6 sialylated glycan receptors (human receptors. Here we report that a single point mutation (Ile219→Lys; a base pair change in the glycan receptor-binding site (RBS of a representative 2009 H1N1 influenza A virus, A/California/04/09 or CA04/09, quantitatively increases its human receptor-binding affinity. The increased human receptor-affinity is in the same range as that of the HA from highly transmissible seasonal and 1918 pandemic H1N1 viruses. Moreover, a 2009 H1N1 virus carrying this mutation in the RBS (generated using reverse genetics transmits efficiently in ferrets by respiratory droplets thereby reestablishing our previously observed correlation between human receptor-binding affinity and transmission efficiency. These findings are significant in the context of monitoring the evolution of the currently circulating 2009 H1N1 viruses.

  19. Circulating cytokines and cytokine receptors in infliximab treatment failure due to TNF-α independent Crohn disease

    DEFF Research Database (Denmark)

    Steenholdt, Casper; Coskun, Mehmet; Buhl, Sine

    2016-01-01

    -IFX antibodies. Circulating cytokines and cytokine receptors were assessed by enzyme-linked immunosorbent assay: granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-1α, IL-1β, IL-1Ra, IL-6, IL-10, IL-12p70, soluble TNF receptor (sTNF-R) 1, sTNF-R2, IL-17A, and monocyte chemotactic...

  20. Human Clade 2.3.4.4 A/H5N6 Influenza Virus Lacks Mammalian Adaptation Markers and Does Not Transmit via the Airborne Route between Ferrets.

    Science.gov (United States)

    Herfst, Sander; Mok, Chris K P; van den Brand, Judith M A; van der Vliet, Stefan; Rosu, Miruna E; Spronken, Monique I; Yang, Zifeng; de Meulder, Dennis; Lexmond, Pascal; Bestebroer, Theo M; Peiris, J S Malik; Fouchier, Ron A M; Richard, Mathilde

    2018-01-01

    Since their emergence in 1997, A/H5N1 influenza viruses of the A/goose/Guangdong/1/96 lineage have diversified in multiple genetic and antigenic clades upon continued circulation in poultry in several countries in Eurasia and Africa. Since 2009, reassortant viruses carrying clade 2.3.4.4 hemagglutinin (HA) and internal and neuraminidase (NA) genes of influenza A viruses of different avian origin have been detected, yielding various HA-NA combinations, such as A/H5N1, A/H5N2, A/H5N3, A/H5N5, A/H5N6, and A/H5N8. Previous studies reported on the low pathogenicity and lack of airborne transmission of A/H5N2 and A/H5N8 viruses in the ferret model. However, although A/H5N6 viruses are the only clade 2.3.4.4 viruses that crossed the species barrier and infected humans, the risk they pose for human health remains poorly characterized. Here, the characterization of A/H5N6 A/Guangzhou/39715/2014 virus in vitro and in ferrets is described. This A/H5N6 virus possessed high polymerase activity, mediated by the E627K substitution in the PB2 protein, which corresponds to only one biological trait out of the three that were previously shown to confer airborne transmissibility to A/H5N1 viruses between ferrets. This might explain its lack of airborne transmission between ferrets. After intranasal inoculation, A/H5N6 virus replicated to high titers in the respiratory tracts of ferrets and was excreted for at least 6 days. Moreover, A/H5N6 virus caused severe pneumonia in ferrets upon intratracheal inoculation. Thus, A/H5N6 virus causes a more severe disease in ferrets than previously investigated clade 2.3.4.4 viruses, but our results demonstrate that the risk from airborne spread is currently low. IMPORTANCE Avian influenza A viruses are a threat to human health, as they cross the species barrier and infect humans occasionally, often with severe outcome. The antigenic and genetic diversity of A/H5 viruses from the A/goose/Guangdong/1/96 lineage is increasing, due to continued