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Sample records for neutralizing igm response

  1. The neutralizing role of IgM during early Chikungunya virus infection

    Science.gov (United States)

    Chua, Chong-Long; Chiam, Chun-Wei; Chan, Yoke-Fun

    2017-01-01

    The antibody isotype IgM appears earlier than IgG, within days of onset of symptoms, and is important during the early stages of the adaptive immune response. Little is known about the functional role of IgM during infection with chikungunya virus (CHIKV), a recently reemerging arbovirus that has caused large global outbreaks. In this study, we studied antibody responses in 102 serum samples collected during CHIKV outbreaks in Malaysia. We described the neutralizing role of IgM at different times post-infection and examined the independent contributions of IgM and IgG towards the neutralizing capacity of human immune sera during the early phase of infection, including the differences in targets of neutralizing epitopes. Neutralizing IgM starts to appear as early as day 4 of symptoms, and their appearance from day 6 is associated with a reduction in viremia. IgM acts in a complementary manner with the early IgG, but plays the main neutralizing role up to a point between days 4 and 10 which varies between individuals. After this point, total neutralizing capacity is attributable almost entirely to the robust neutralizing IgG response. IgM preferentially binds and targets epitopes on the CHIKV surface E1-E2 glycoproteins, rather than individual E1 or E2. These findings provide insight into the early antibody responses to CHIKV, and have implications for design of diagnostic serological assays. PMID:28182795

  2. The IgM Response to Modified LDL in Experimental Atherosclerosis Hypochlorite-modified LDL IgM Antibodies versus Classical Natural T15 IgM Antibodies

    NARCIS (Netherlands)

    van Leeuwen, Marcella; Damoiseaux, Jan; Duijvestijn, Adriaan; Heeringa, Peter; Gijbels, Marion; de Winther, Menno; Tervaert, Jan Willem Cohen; Shoenfeld, Y; Gershwin, ME

    2009-01-01

    Introduction: It is hypothesized that IgM antibodies to oxidized LDL are anti-atherogenic. Myeloperoxidase from plaque-infiltrating neutrophils catalyzes the production of hypochlorite (HOCl), which oxidizes LDL. Here we study the IgM response to HOCl-modified LDL in comparison to titers of T15 clon

  3. HOW TO SEARCH FOR ISLANDS OF NEUTRAL HYDROGEN IN THE z ∼ 5.5 IGM

    Energy Technology Data Exchange (ETDEWEB)

    Malloy, Matthew; Lidz, Adam, E-mail: mattma@sas.upenn.edu [Department of Physics and Astronomy, University of Pennsylvania, 209 South 33rd Street, Philadelphia, PA 19104 (United States)

    2015-02-01

    Observations of the Lyman-alpha (Lyα) forest may allow reionization to complete as late as z ∼ 5.5, provided the ionization state of the intergalactic medium (IGM) is sufficiently inhomogeneous at these redshifts. In this case, significantly neutral islands may remain among highly ionized gas with the ionized regions allowing some transmission through the Lyα forest. This possibility has the important virtue that it is eminently testable with existing Lyα forest data. In particular, we describe three observable signatures of significantly neutral gas in the z ∼ 5.5 IGM. We use mock quasar spectra produced from numerical simulations of reionization to develop these tests. First, we quantify how the abundance and length of absorbed regions in the forest increase with the volume-averaged neutral fraction in our reionization model. Second, we consider stacking the transmission profile around highly absorbed regions in the forest. If and only if there is significantly neutral gas in the IGM, absorption in the damping wing of the Lyα line will cause the transmission to recover slowly as one moves from absorbed to transmitted portions of the spectrum. Third, the deuterium Lyβ line should imprint a small but distinctive absorption feature slightly blueward of absorbed neutral regions in the Lyβ forest. We show that these tests can be carried out with existing Keck HIRES spectra at z ∼ 5.5, with the damping wing being observable for 〈x{sub H} {sub I}〉≳0.05 and the deuterium feature observable with additional high-resolution spectra for 〈x{sub H} {sub I}〉≳0.2.

  4. Postsplenectomy cytomegaloviral mononucleosis: marked lymphocytosis, TCRgamma gene rearrangements, and impaired IgM response.

    Science.gov (United States)

    Han, Xiang Y; Lin, Pei; Amin, Hesham M; Ferrajoli, Alessandra

    2005-04-01

    People who have undergone splenectomy mount a poor IgM response to bacterial polysaccharide vaccines. Whether this defect is true during natural bacterial and viral infections is unknown. We present 2 cases of postsplenectomy cytomegalovirus (CMV)-induced mononucleosis with impaired IgM but normal to augmented IgG response. The cases presented initial diagnostic challenges owing to a prolonged course of infection, marked lymphocytosis (peak lymphocyte count, 27,900/microL [27.9 10(9)/L]), clonal T-cell proliferation with T-cell receptor g gene rearrangements, and remote history of splenectomy. However, the acute nature of the infections, serial determinations of the anti-CMV IgM and IgG, exclusion of other causes, and detection of CMV in the blood established the diagnosis and revealed the deranged antibody response. The infections resolved without specific treatment. These cases suggest that the spleen might be a primary site for specific anti-CMV IgM response.

  5. IgM response to a human Pneumocystis carinii surface antigen in HIV-infected patients with pulmonary symptoms

    DEFF Research Database (Denmark)

    Lundgren, Bettina; Kovacs, J A; Mathiesen, Lars Reinhardt

    1993-01-01

    95. Four of the 5 patients with IgM antibodies also had IgG antibodies to gp95 and microbiologically proven P. carinii pneumonia (PCP). In 76/128 patients for whom serial samples were available, changes in antibody response were determined. In 3 patients we demonstrated an increase in IgM antibody...... response to gp95. These patients also showed an increase in IgG antibodies to gp95 and had microbiologically proven PCP. Prior to the development of the IgM response, IgG antibodies to gp95 were detectable in all 3 patients. Thus, HIV-infected patients with PCP seldom produce IgM antibodies to the major...... human P. carinii surface antigen. The increase in IgM response during the course of PCP observed in 3 patients suggests either reinfection with a new strain, or antigenic drift of an already acquired strain of P. carinii....

  6. VH and VL Domains of Polyspecific IgM and Monospecific IgG Antibodies Contribute Differentially to Antigen Recognition and Virus Neutralization Functions.

    Science.gov (United States)

    Pasman, Y; Kaushik, A K

    2016-07-01

    We analysed contributions of variable heavy (FdVH ) and variable light (FdVL ) domains in comparison to scFv (FdVH +FdVL ) of naturally occurring polyspecific bovine IgM with an exceptionally long CDR3H and an induced monospecific bovine herpes virus-1 (BoHV-1) neutralizing IgG1 antibody in the context of to antigen-binding site and antibody function. Various recombinant FdVH , FdVL and scFv were constructed and expressed in Pichia pastoris from the bovine IgM and IgG1 antibody encoding cDNA. The scFv1H12 showed polyspecific antigen binding similar to parent IgM antibody, though subtle differences, for example, higher thyroglobulin recognition. Such differences reflect influence of the constant region on the antigen-binding site configuration. Unlike, variable light domain FdVL 1H12, the variable heavy domain FdVH 1H12 alone recognized multiple antigens that differed from the recognition pattern of scFv1H12 (FdVH +FdVL ) and the parent IgM antibody. Nonetheless, role of FdVL 1H12 in providing structural support to FdVH in antigen recognition is noted, apart from its intrinsic antigen recognition ability. Surface plasmon resonance analysis revealed low to moderate affinity of scFv1H12 to IgG antigen. By contrast, the individual FdVH 073 and FdVL 074, originating from induced BoHV-1 neutralizing IgG1 antibody, recognized target epitope on BoHV-1 weakly when compared to FdVH +FdVL (scFv3-18L). Interestingly, both the FdVH and FdVL domains of induced IgG antibody are required to achieve BoHV-1 neutralization. To conclude, there exist subtle functional differences in the contribution of FdVH and FdVL to antigen-binding site generation of polyspecific IgM and monospecific IgG antibodies relevant to antigen recognition and virus neutralization functions.

  7. Humoral immune response of dogs after vaccination against leptospirosis measured by an IgM- and IgG-specific ELISA

    NARCIS (Netherlands)

    Hartman, E.G.; Houten, M. van; Frik, J.F.; Donk, A. van der

    1984-01-01

    An IgM- and IgG-specific ELISA was used to measure the antibody response stimulated in dogs by vaccination with a leptospiral bacterin containing chemically inactivated serotype icterohaemorrhagiae and serotype canicola leptospires. All dogs produced anti-leptospiral IgM and IgG. The IgM production

  8. Genetic Resistance to Malaria Is Associated With Greater Enhancement of Immunoglobulin (Ig)M Than IgG Responses to a Broad Array of Plasmodium falciparum Antigens

    Science.gov (United States)

    Arama, Charles; Skinner, Jeff; Doumtabe, Didier; Portugal, Silvia; Tran, Tuan M.; Jain, Aarti; Traore, Boubacar; Doumbo, Ogobara K.; Davies, David Huw; Troye-Blomberg, Marita; Dolo, Amagana; Felgner, Philip L.; Crompton, Peter D.

    2015-01-01

    Background. People of the Fulani ethnic group are more resistant to malaria compared with genetically distinct ethnic groups, such as the Dogon people, in West Africa, and studies suggest that this resistance is mediated by enhanced antibody responses to Plasmodium falciparum antigens. However, prior studies measured antibody responses to <0.1% of P falciparum proteins, so whether the Fulani mount an enhanced and broadly reactive immunoglobulin (Ig)M and IgG response to P falciparum remains unknown. In general, little is known about the extent to which host genetics influence the overall antigen specificity of IgM and IgG responses to natural infections. Methods. In a cross-sectional study in Mali, we collected plasma from asymptomatic, age-matched Fulani (n = 24) and Dogon (n = 22) adults with or without concurrent P falciparum infection. We probed plasma against a protein microarray containing 1087 P falciparum antigens and compared IgM and IgG profiles by ethnicity. Results. We found that the breadth and magnitude of P falciparum-specific IgM and IgG responses were significantly higher in the malaria-resistant Fulani versus the malaria-susceptible Dogon, and, unexpectedly, P falciparum-specific IgM responses more strongly distinguished the 2 ethnic groups. Conclusions. These findings point to an underappreciated role for IgM in protection from malaria, and they suggest that host genetics may influence the antigen specificity of IgM and IgG responses to infection. PMID:26361633

  9. Shift in epitope dominance of IgM and IgG responses to Plasmodium falciparum MSP1 block 4

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    Leke Rose GF

    2010-01-01

    Full Text Available Abstract Background Plasmodium falciparum merozoite surface protein-1 (MSP1 has been extensively studied as a blood-stage malaria vaccine candidate, with most work focused on the conserved 19 kDa and semi-conserved 42 kDa C-terminal regions (blocks 16-17 and the hypervariable N-terminal repeat region (block 2. However, recent genotyping studies suggest that additional regions of MSP1 may be under selective pressure, including a locus of intragenic recombination designated as block 4 within the 3' region of the gene. Methods The current study examined the antibody response to the two parental and two recombinant forms of block 4 and to blocks 16-17 (3D7 in study populations from Colombia, Papua New Guinea and Cameroon that differ in malaria transmission intensity and ethnic composition. Results IgM and IgG antibodies were detected against parental and recombinant MSP1 block 4 peptides in all three populations. Overall, 32-44% of the individuals produced IgM to one or more of the peptides, with most individuals having IgM antibodies reactive with both parental and recombinant forms. In contrast, IgG seropositivity to block 4 varied among populations (range 15-65%, with the majority of antibodies showing specificity for one or a pair of block 4 peptides. The IgG response to block 4 was significantly lower than that to blocks 16-17, indicating block 4 is subdominant. Antibodies to block 4 and blocks 16-17 displayed distinct IgG subclass biases, with block 4 responses biased toward IgG3 and blocks 16-17 toward IgG1. These patterns of responsiveness were consistently observed in the three study populations. Conclusions Production of antibodies specific for each parental and recombinant MSP1 block 4 allele in different populations exposed to P. falciparum is consistent with balancing selection of the MSP1 block 4 region by the immune response of individuals in areas of both low and high malaria transmission. MSP1 block 4 determinants may be important

  10. Genetic Resistance to Malaria Is Associated With Greater Enhancement of Immunoglobulin (Ig)M Than IgG Responses to a Broad Array of Plasmodium falciparum Antigens.

    Science.gov (United States)

    Arama, Charles; Skinner, Jeff; Doumtabe, Didier; Portugal, Silvia; Tran, Tuan M; Jain, Aarti; Traore, Boubacar; Doumbo, Ogobara K; Davies, David Huw; Troye-Blomberg, Marita; Dolo, Amagana; Felgner, Philip L; Crompton, Peter D

    2015-09-01

    Background.  People of the Fulani ethnic group are more resistant to malaria compared with genetically distinct ethnic groups, such as the Dogon people, in West Africa, and studies suggest that this resistance is mediated by enhanced antibody responses to Plasmodium falciparum antigens. However, prior studies measured antibody responses to Dogon (n = 22) adults with or without concurrent P falciparum infection. We probed plasma against a protein microarray containing 1087 P falciparum antigens and compared IgM and IgG profiles by ethnicity. Results.  We found that the breadth and magnitude of P falciparum-specific IgM and IgG responses were significantly higher in the malaria-resistant Fulani versus the malaria-susceptible Dogon, and, unexpectedly, P falciparum-specific IgM responses more strongly distinguished the 2 ethnic groups. Conclusions.  These findings point to an underappreciated role for IgM in protection from malaria, and they suggest that host genetics may influence the antigen specificity of IgM and IgG responses to infection.

  11. Comparison of IgM, IgG1 and IgG2 responses to Trichinella spiralis and Trichinella britovi in swine

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    Serrano F.J

    2001-06-01

    Full Text Available Pigs infected with T. spiralis and T. britovi were followed by double (lgG and triple antibody ELISA (IgG1, lgG 2 and IgM during a 12-week-period. Specific IgG and IgG1 responses were similar and showed a significant relation with the infecting doses and intensity of infection. Response to T. britovi was slightly lower than in groups infected with the same dose of T. spiralis. lgG 2 response was weak and almost undetectable in the lowest infected pigs, but relationship with the intensity of infection was unclear. IgM antibodies showed rapid but transient increases, generally simultaneous to peaks of IgG response.

  12. Heterozygous Mutation in IκBNS Leads to Reduced Levels of Natural IgM Antibodies and Impaired Responses to T-Independent Type 2 Antigens.

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    Pedersen, Gabriel K; Ádori, Monika; Stark, Julian M; Khoenkhoen, Sharesta; Arnold, Carrie; Beutler, Bruce; Karlsson Hedestam, Gunilla B

    2016-01-01

    Mice deficient in central components of classical NF-κB signaling have low levels of circulating natural IgM antibodies and fail to respond to immunization with T-independent type 2 (TI-2) antigens. A plausible explanation for these defects is the severely reduced numbers of B-1 and marginal zone B (MZB) cells in such mice. By using an ethyl-N-nitrosourea mutagenesis screen, we identified a role for the atypical IκB protein IκBNS in humoral immunity. IκBNS-deficient mice lack B-1 cells and have severely reduced numbers of MZB cells, and thus resemble several other strains with defects in classical NF-κB signaling. We analyzed mice heterozygous for the identified IκBNS mutation and demonstrate that these mice have an intermediary phenotype in terms of levels of circulating IgM antibodies and responses to TI-2 antigens. However, in contrast to mice that are homozygous for the IκBNS mutation, the heterozygous mice had normal frequencies of B-1 and MZB cells. These results suggest that there is a requirement for IκBNS expression from two functional alleles for maintaining normal levels of circulating natural IgM antibodies and responses to TI-2 antigens.

  13. IGMS Construction Grants Overview

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    The Integrated Grants Management System (IGMS) is a web-based system that contains information on the recipient of the grant, fellowship, cooperative agreement and interagency agreement, including the name of the entity accepting the award.

  14. Social Responsibility (III): The Myth of the Neutrality of Science

    Science.gov (United States)

    Rose, Steven; Rose, Hilary

    1971-01-01

    "Even pure research can never be neutral since its nature and its directions are always framed by the social and scientific context of its time...(Therefore, scientists are)...profoundly responsible to society in the performance of their work." (Author/AL)

  15. IgM, IgA, IgG1 and IgG2 specific responses in blood and gut secretion of calves fed soyabean products.

    Science.gov (United States)

    Dréau, D; Lallès, J P; Salmon, H; Toullec, R

    1995-07-01

    Calves fed soya proteins may develop severe gastrointestinal disorders. Whether these are predominantly associated with particular Ig subclasses and (or) dietary proteins remains unclear. Therefore, antibody responses to soyabean protein were analysed by dot- and blot-immunobinding in plasma and intestinal mucous secretions. One-month-old calves were fed for 2.5 months liquid diets based on skim milk powder (SMP) or a mixture (2:3, protein basis) of whey and soyabean products including a low antigenic hydrolysed soya protein isolate (HSPI) and a highly antigenic heated soya flour (HSF). Specific antibodies (Abs) of the main isotypes (IgM, IgA, IgG1, IgG2) were characterised by immunostaining of samples which had been previously incubated with nitrocellulose sheets coated with SMP, HSPI or HSF extracts. Plasma collected before feeding experimental diets showed very little specific Abs. By contrast, 2.5 months later, a three-fold increase (P IgA titres against HSF antigens was observed in calves fed HSF compared with those fed the control or HSPI diet. IgG1 immunoblotting revealed many protein bands from soya in the molecular range of 22-32 and 38-42 kDa. Immunorecognition of specific proteins from SMP and HSPI remained low and similar among animal groups. Specific IgM, IgA and IgG1 titres against HSF, and to a lesser extent HSPI, were significantly higher (P IgA and IgG1. By contrast, only weak bands were found for IgM and IgG2 in all groups of calves. Thus, calves fed antigenic HSF do present specific Abs including IgG1 and IgA isotypes, both systemically and locally. Therefore, IgG1 and (or) IgA rather than IgM and IgG2 Abs may be preferred for assessing the immunogenicity of soyabean products in calves. Interestingly, soyabean immunogenicity was drastically reduced by adequate proteolysis.

  16. Reatividade do anticorpo IgM anti-Treponema pallidum na soroconversão e na resposta sorológica ao tratamento de sífilis IgM antibody reactivity to Treponema pallidum in seroconversion and in the serologic response to syphilis treatment

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    Neuza Satomi Sato

    2012-12-01

    Full Text Available INTRODUÇÃO: A utilidade da detecção de anticorpos da imunoglobulina da classe M (IgM no diagnóstico da sífilis tem sido discutida há tempos. OBJETIVO: No presente estudo foi analisada a ocorrência de anticorpo IgM anti-T. pallidum (Tp-IgMAc nas amostras de pacientes com sífilis recente, na fase de soroconversão e no monitoramento da resposta sorológica pós-tratamento. MÉTODOS: Amostras séricas de 11 indivíduos. RESULTADOS: Na soroconversão, o Tp-IgMAc foi detectado nas amostras de 10 indivíduos, e em um paciente a reatividade IgM ocorreu anteriormente ao Venereal Disease Research Laboratory (VDRL. A sororreversão foi evidenciada nas amostras de três pacientes com sífilis secundária tratada, e em um indivíduo com reinfecção. CONCLUSÃO: A detecção de Tp-IgMAc mostrou ser um potencial marcador diagnóstico de sífilis ativa e o desempenho do ensaio imunoenzimático de captura de IgM (ELISA-IgM para o monitoramento pós-tratamento foi similar ao da VDRL.INTRODUCTION: The appropriateness of IgM antibody detection in the diagnosis of syphilis has been extensively discussed. OBJECTIVE: This study aimed at assessing the detection of anti-T. pallidum IgM antibody (TP-IgMAb in serum samples from patients with recent syphilis in seroconversion and in the monitoring of post-treatment serological response. METHODS: Serum samples from 11 individuals. RESULTS: At seroconversion, positive Tp-IgMAb was detected in 10 samples and IgM reactivity previous to Venereal Disease Research Laboratory (VDRL was detected in one sample. Seroreversion was found in samples from three treated patients with secondary syphilis and in one individual with reinfection. CONCLUSION: Tp-IgMAb detection proved to be a potential diagnostic marker for active syphilis, and IgM capture enzyme linked immunosorbent assay (ELISA-IgM performance was similar to VDRL in post-treatment monitoring.

  17. Experimental infection in cattle: kinetics of production of IgM and IgG against bovine cysticercosis and inflammatory response

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    Rafaella Paola Meneguete dos Guimarães-Peixoto

    2015-04-01

    Full Text Available Bovine cysticercosis is a zoonosis that affects humans in their adult form (taeniasis and its larval is found inserted in the musculature of infected cattle (cysticerci. It is still not entirely clear how animal immune response against infection occurs, being the comprehension of this process necessary for the enhancement of diagnostic capacity and disease prevention. This work aimed to evaluate the evolution of the immune response in experimentally infected cattle, compared with findings in cell response by optical microscopy. Nine animals were infected at a rate of 120,000 eggs of Taenia saginata. Five of the animals were similar in the kinetics of antibody production against cysticerci, with maximal levels of IgG and IgM. The other four animals showed an immune response different from the majority, with two of them showing delayed response to infection by cysticerci while the others apparently did not have initial contact with antigens secreted by cysticerci. Regarding the cellular response, it was found that, in lesions of viable cysticerci, inflammatory cells predominated, whereas in nonviable cysticerci there were tissue repair cells in the most part, being possible to notice that the amount of migratory calcareous corpuscles are related to the death stage of the parasite. These findings are important for the understanding immune response of cattle infected with cysticercosis.

  18. A single autosomal gene defect severely limits IgG but not IgM responses in B lymphocyte-deficient A/WySnJ mice.

    Science.gov (United States)

    Miller, D J; Hanson, K D; Carman, J A; Hayes, C E

    1992-02-01

    Antigen-stimulated B lymphocytes either differentiate into IgM-secreting plasma cells or into memory B cells that secrete other immunoglobulin isotypes upon antigen restimulation. The mechanisms that generate and maintain memory B cells are poorly understood. Previously, we described a severe B lymphocyte deficiency in adult strain A/WySnJ mice compared to subline A/J. Here we show that the single, autosomal co-dominant locus responsible for the deficiency also diminishes IgG-secreting B cell formation without interfering with IgM-secreting plasma cell differentiation. A/WySnJ secondary IgG1 responses to the protein antigens hemocyanin, bovine gamma-globulin, ovalbumin, lysozyme and beta-galactosidase were 6- to 50-fold lower than A/J responses. The defect also decreased secondary IgG2a and IgG3 responses, and primary IgG1 and IgG2a responses. The reduced A/WySnJ secondary IgG1 response was not due to differential response kinetics or dose responsiveness, and could not be augmented to A/J levels by repeated immunizations. Serum IgG1, IgG2a and IgG3 levels from nonimmune A/WySnJ mice were similarly reduced. The secondary IgG1 response and splenic B cell percentage showed significant positive correlation (r = 0.72) in F2 mice, suggesting that a single locus controlled both traits. In contrast, A/WySnJ mice made good primary IgM responses to hemocyanin, beta-galactosidase, and the thymus-independent antigen trinitrophenyl-Ficoll. The A/WySnJ splenic adherent cells were competent in antigen-presenting function, and A/WySnJ immune T cells proliferated in response to antigen and provided the requisite B cell stimulatory signals for an IgG1 response. Together, our results suggest that A/WySnJ mice have a genetic lesion that causes a selective IgG immune response dysfunction. The absence of IgG-secreting cell precursors or a defect in precursor activation or differentiation are two possible mechanisms which could precipitate a selective IgG response dysfunction. We propose

  19. Deletion of WASp and N-WASp in B cells cripples the germinal center response and results in production of IgM autoantibodies.

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    Dahlberg, Carin I M; Torres, Magda-Liz; Petersen, Sven H; Baptista, Marisa A P; Keszei, Marton; Volpi, Stefano; Grasset, Emilie K; Karlsson, Mikael C I; Walter, Jolan E; Snapper, Scott B; Notarangelo, Luigi D; Westerberg, Lisa S

    2015-08-01

    Humoral immunodeficiency caused by mutations in the Wiskott-Aldrich syndrome protein (WASp) is associated with failure to respond to common pathogens and high frequency of autoimmunity. Here we addressed the question how deficiency in WASp and the homologous protein N-WASp skews the immune response towards autoreactivity. Mice devoid of WASp or both WASp and N-WASp in B cells formed germinal center to increased load of apoptotic cells as a source of autoantigens. However, the germinal centers showed abolished polarity and B cells retained longer and proliferated less in the germinal centers. While WASp-deficient mice had high titers of autoreactive IgG, B cells devoid of both WASp and N-WASp produced mainly IgM autoantibodies with broad reactivity to autoantigens. Moreover, B cells lacking both WASp and N-WASp induced somatic hypermutation at reduced frequency. Despite this, IgG1-expressing B cells devoid of WASp and N-WASp acquired a specific high affinity mutation, implying an increased BCR signaling threshold for selection in germinal centers. Our data provides evidence for that N-WASp expression alone drives WASp-deficient B cells towards autoimmunity.

  20. The anti-cancer IgM monoclonal antibody PAT-SM6 binds with high avidity to the unfolded protein response regulator GRP78.

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    Zachary Rosenes

    Full Text Available The monoclonal IgM antibody PAT-SM6 derived from human tumours induces apoptosis in tumour cells and is considered a potential anti-cancer agent. A primary target for PAT-SM6 is the unfolded protein response regulator GRP78, over-expressed externally on the cell surface of tumour cells. Small angle X-ray scattering (SAXS studies of human GRP78 showed a two-domain dumbbell-shaped monomer, while SAXS analysis of PAT-SM6 revealed a saucer-shaped structure accommodating five-fold symmetry, consistent with previous studies of related proteins. Sedimentation velocity analysis of GRP78 and PAT-SM6 mixtures indicated weak complex formation characterized by dissociation constants in the high micromolar concentration range. In contrast, enzyme-linked immunosorbant assays (ELISAs showed strong and specific interactions between PAT-SM6 and immobilized GRP78. The apparent binding constant estimated from a PAT-SM6 saturation curve correlated strongly with the concentration of GRP78 used to coat the microtiter tray. Experiments using polyclonal antiGRP78 IgG antibodies or a monoclonal IgG derivative of PAT-SM6 did not show a similar dependence. Competition experiments with soluble GRP78 indicated more effective inhibition of PAT-SM6 binding at low GRP78 coating concentrations. These observations suggest an avidity-based binding mechanism that depends on the multi-point attachment of PAT-SM6 to GRP78 clustered on the surface of the tray. Analysis of ELISA data at high GRP78 coating concentrations yielded an apparent dissociation constant of approximately 4 nM. We propose that the biological action of PAT-SM6 in tumour cell apoptosis may depend on the multivalent nature of PAT-SM6 and the high avidity of its interaction with multiple GRP78 molecules clustered on the tumour cell surface.

  1. Mechanisms of equine infectious anemia virus escape from neutralizing antibody responses define epitope specificity.

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    Sponseller, Brett A; Clark, Sandra K; Friedrich, Rachel A

    2012-08-01

    Determining mechanisms of viral escape to particular epitopes recognized by virus-neutralizing antibody can facilitate characterization of host-neutralizing antibody responses as type- versus group-specific, and provides necessary information for vaccine development. Our study reveals that a single N-glycan located in the 5' region of the Wyoming wild-type equine infectious anemia virus (EIAV) principal neutralizing domain (PND) accounts for the differences in neutralization phenotype observed between PND variants, while variations in charged amino acids within the PND do not appear to play a key role in viral escape. Site-directed mutagenesis and peptide mapping of a conserved epitope to neutralizing antibody in the 3' region of the PND showed rapid selective pressure for acquisition of a 5' PND N-glycan responsible for defining the specificity of the neutralizing-antibody response.

  2. Hypophysectomy and Neurointermediate Pituitary Lobectomy Reduce Serum Immunoglobulin M (IgM) and IgG and Intestinal IgA Responses to Salmonella enterica Serovar Typhimurium Infection in Rats

    Science.gov (United States)

    Campos-Rodríguez, Rafael; Quintanar-Stephano, Andrés; Jarillo-Luna, Rosa Adriana; Oliver-Aguillón, Gabriela; Ventura-Juárez, Javier; Rivera-Aguilar, Victor; Berczi, Istvan; Kovacs, Kalman

    2006-01-01

    The influence of anterior pituitary hormones on the gastrointestinal tract of humans and animals has been reported. Hypophysectomy (HYPOX) in the rat causes atrophy of the intestinal mucosa, reduction of gastric secretion and intestinal absorption, and increased susceptibility to infections. To our knowledge, there are no studies on the humoral immune response of the gut-associated lymphoid tissue after HYPOX. We have reported that decreased secretion of vasopressin and oxytocin due to neurointermediate pituitary lobectomy (NIL) diminishes humoral and cell-mediated immune responses. However, no data have been published on whether NIL can affect intestinal immune responses. We analyzed the effects of HYPOX and NIL on bacterial colonization of the intestinal lumen, Peyer's patches, and spleen as well as the serum immunoglobulin G (IgG) and IgM and specific intestinal IgA levels in response to Salmonella enterica serovar Typhimurium oral infection. Results showed the following: (i) Salmonella serovar Typhimurium was eliminated from the intestinal lumen at the same rate in rats that underwent a sham operation, HYPOX, and NIL; (ii) Salmonella serovar Typhimurium colonization of Peyer's patches and spleen was significantly higher in both HYPOX and NIL rats than in sham-operated rats; (iii) serum IgG and IgM and intestinal IgA against surface proteins of Salmonella serovar Typhimurium were significantly lower in HYPOX and NIL rats than in sham-operated rats; and (iv) compared to NIL rats, higher Peyer's patch and spleen bacterial colonization and decreased IgG, IgM, and IgA production were observed in HYPOX rats. We conclude that hormones from each pituitary lobe affect the systemic and gastrointestinal humoral immune responses through different mechanisms. PMID:16495563

  3. In vitro neutralization of viral hemorrhagic septicemia virus by plasma from immunized zebrafish

    NARCIS (Netherlands)

    Chinchilla, B.; Gomez-Casado, E.; Encinas, P.; Falco Gracia, J.A.; Estepa, A.; Coll, J.

    2013-01-01

    We studied humoral long-term adaptive viral neutralization responses in zebrafish (Danio rerio), an increasingly useful vertebrate model for viral diseases actually limited by the absence of standardized anti-zebrafish immunoglobulin M (IgM) antibodies. We established an alternative method, similar

  4. Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort.

    Science.gov (United States)

    Landais, Elise; Huang, Xiayu; Havenar-Daughton, Colin; Murrell, Ben; Price, Matt A; Wickramasinghe, Lalinda; Ramos, Alejandra; Bian, Charoan B; Simek, Melissa; Allen, Susan; Karita, Etienne; Kilembe, William; Lakhi, Shabir; Inambao, Mubiana; Kamali, Anatoli; Sanders, Eduard J; Anzala, Omu; Edward, Vinodh; Bekker, Linda-Gail; Tang, Jianming; Gilmour, Jill; Kosakovsky-Pond, Sergei L; Phung, Pham; Wrin, Terri; Crotty, Shane; Godzik, Adam; Poignard, Pascal

    2016-01-01

    Broadly neutralizing antibodies (bnAbs) are thought to be a critical component of a protective HIV vaccine. However, designing vaccines immunogens able to elicit bnAbs has proven unsuccessful to date. Understanding the correlates and immunological mechanisms leading to the development of bnAb responses during natural HIV infection is thus critical to the design of a protective vaccine. The IAVI Protocol C program investigates a large longitudinal cohort of primary HIV-1 infection in Eastern and South Africa. Development of neutralization was evaluated in 439 donors using a 6 cross-clade pseudo-virus panel predictive of neutralization breadth on larger panels. About 15% of individuals developed bnAb responses, essentially between year 2 and year 4 of infection. Statistical analyses revealed no influence of gender, age or geographical origin on the development of neutralization breadth. However, cross-clade neutralization strongly correlated with high viral load as well as with low CD4 T cell counts, subtype-C infection and HLA-A*03(-) genotype. A correlation with high overall plasma IgG levels and anti-Env IgG binding titers was also found. The latter appeared not associated with higher affinity, suggesting a greater diversity of the anti-Env responses in broad neutralizers. Broadly neutralizing activity targeting glycan-dependent epitopes, largely the N332-glycan epitope region, was detected in nearly half of the broad neutralizers while CD4bs and gp41-MPER bnAb responses were only detected in very few individuals. Together the findings suggest that both viral and host factors are critical for the development of bnAbs and that the HIV Env N332-glycan supersite may be a favorable target for vaccine design.

  5. Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting

    OpenAIRE

    Doria-Rose, Nicole A.; Altae-Tran, Han R.; Roark, Ryan S.; Schmidt, Stephen D.; Sutton, Matthew S.; Louder, Mark K.; Chuang, Gwo-Yu; Bailer, Robert T.; Cortez, Valerie; Kong, Rui; McKee, Krisha; O’Dell, Sijy; Wang, Felicia; Abdool Karim, Salim S.; Binley, James M.

    2017-01-01

    Computational neutralization fingerprinting, NFP, is an efficient and accurate method for predicting the epitope specificities of polyclonal antibody responses to HIV-1 infection. Here, we present next-generation NFP algorithms that substantially improve prediction accuracy for individual donors and enable serologic analysis for entire cohorts. Specifically, we developed algorithms for: (a) selection of optimized virus neutralization panels for NFP analysis, (b) estimation of NFP prediction c...

  6. Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort.

    Directory of Open Access Journals (Sweden)

    Elise Landais

    2016-01-01

    Full Text Available Broadly neutralizing antibodies (bnAbs are thought to be a critical component of a protective HIV vaccine. However, designing vaccines immunogens able to elicit bnAbs has proven unsuccessful to date. Understanding the correlates and immunological mechanisms leading to the development of bnAb responses during natural HIV infection is thus critical to the design of a protective vaccine. The IAVI Protocol C program investigates a large longitudinal cohort of primary HIV-1 infection in Eastern and South Africa. Development of neutralization was evaluated in 439 donors using a 6 cross-clade pseudo-virus panel predictive of neutralization breadth on larger panels. About 15% of individuals developed bnAb responses, essentially between year 2 and year 4 of infection. Statistical analyses revealed no influence of gender, age or geographical origin on the development of neutralization breadth. However, cross-clade neutralization strongly correlated with high viral load as well as with low CD4 T cell counts, subtype-C infection and HLA-A*03(- genotype. A correlation with high overall plasma IgG levels and anti-Env IgG binding titers was also found. The latter appeared not associated with higher affinity, suggesting a greater diversity of the anti-Env responses in broad neutralizers. Broadly neutralizing activity targeting glycan-dependent epitopes, largely the N332-glycan epitope region, was detected in nearly half of the broad neutralizers while CD4bs and gp41-MPER bnAb responses were only detected in very few individuals. Together the findings suggest that both viral and host factors are critical for the development of bnAbs and that the HIV Env N332-glycan supersite may be a favorable target for vaccine design.

  7. Initial study of neutral post-instruction responses on the Maryland Physics Expectation Survey

    Science.gov (United States)

    Saltzman, J.; Price, M. F.; Rogers, M. B.

    2016-06-01

    Epistemological studies generally focus on how students think about their construction of knowledge compared to how experts think about the same ideas. Instruments such as the MPEX and CLASS use a Likert scale to gauge whether students agree or disagree with how experts think about the same ideas. During analysis, five point scale responses are typically reduced to favorable, neutral, and unfavorable with neutral being treated as a nonresponse. What if students are actively selecting neutral and not treating it as a "does not apply?" To address this question we chose to analyze the postinstruction neutral responses of students in our Physics I course using data from multiple years, multiple sections, and multiple instructors. We found that classroom average postinstruction neutral responses were consistently within a band of 15%-25% and that this was also consistent with other published results. It is not yet clear what this pattern means. Is this a measure of students receiving mixed messages from instructors or a measure of a transitional stage that students go through when learning how to be a good college physics student? These initial findings are interesting enough that we are presenting them here with a more detailed question-by-question analysis to be published in the near future. For example, high levels of neutral responses to applied questions (e.g., "All I need to do is. …") may indicate that students are receiving mixed messages from instructors. On the other hand, high levels of neutral responses to conceptual questions (e.g., "Knowledge in physics…") may indicate that students are in a transitional stage between novice and expert.

  8. GRBs as Probes of the IGM

    Science.gov (United States)

    Cucchiara, Antonino; Totani, Tonomori; Tanvir, Nial

    2016-12-01

    Gamma-ray Bursts (GRBs) are the most powerful explosions known, capable of outshining the rest of gamma-ray sky during their short-lived prompt emission. Their cosmological nature makes them the best tool to explore the final stages in the lives of very massive stars up to the highest redshifts. Furthermore, studying the emission from their low-energy counterparts (optical and infrared) via rapid spectroscopy, we have been able to pin down the exact location of the most distant galaxies as well as placing stringent constraints on their host galaxies and intervening systems at low and high-redshift (e.g. metallicity and neutral hydrogen fraction). In fact, each GRB spectrum contains absorption features imprinted by metals in the host interstellar medium (ISM) as well as the intervening intergalactic medium (IGM) along the line of sight. In this chapter we summarize the progress made using a large dataset of GRB spectra in understanding the nature of both these absorbers and how GRBs can be used to study the early Universe, in particular to measure the neutral hydrogen fraction and the escape fraction of UV photons before and during the epoch of re-ionization.

  9. Protective roles of natural IgM antibodies

    Directory of Open Access Journals (Sweden)

    Caroline eGrönwall

    2012-04-01

    Full Text Available Antibodies are a vital part of the armentarium of the adaptive immune system for the fine-tuning of the recognition and response to foreign threats. However, in health there are some types of antibodies that instead recognize self-antigens for the enhancement of primitive innate functions. The repertoire of natural IgM antibodies is postulated to have been selected during immune evolution for their contributions to critical immunoregulatory and housekeeping properties. The clearance of dying cells is one of the most essential responsibilities of the immune system, which is essential to prevent uncontrolled inflammation and autoimmunity. In the murine immune system, natural IgM antibodies that recognize apoptotic cells have been shown to enhance the phagocytic clearance of dead and dying cells and to suppress innate immune signaling pathways. In the mouse, natural IgM are often the products of B-1 cell clones that arise during immune development without an absolute requirement for exogenous antigenic stimulation. In patients with systemic lupus erythemtosus, IgM autoantibodies, which bind to neo-epitopes on apoptotic cells, have been demonstrated to be present at significantly higher levels in patients with lower disease activity and with less severe organ damage. While certain specificities of IgM autoantibodies correlate with protection from lupus renal disease, others may convey protective properties from lupus-associated atherosclerotic cardiovascular disease. New unexpected insights into the functional roles of IgM antibodies are still emerging, especially regarding the functions of natural antibodies. Herein, we review recent progress in our understanding of the potential roles of natural IgM autoantibodies in the regulation of immune homeostasis and for protection from autoimmune and inflammatory diseases.

  10. CD40 Ligand Deficient C57BL/6 Mouse Is a Potential Surrogate Model of Human X-Linked Hyper IgM (X-HIGM Syndrome for Characterizing Immune Responses against Pathogens

    Directory of Open Access Journals (Sweden)

    Catalina Lopez-Saucedo

    2015-01-01

    Full Text Available Individuals with X-HIGM syndrome fail to express functional CD40 ligand; consequently they cannot mount effective protective antibody responses against pathogenic bacteria. We evaluated, compared, and characterized the humoral immune response of wild type (WT and C57-CD40L deficient (C57-CD40L−/− mice infected with Citrobacter rodentium. Basal serum isotype levels were similar for IgM and IgG3 among mice, while total IgG and IgG2b concentrations were significantly lower in C57-CD40L−/− mice compared with WT. Essentially IgG1 and IgG2c levels were detectable only in WT mice. C57-CD40L−/− animals, orally inoculated with 2×109 CFU, presented several clinical manifestations since the second week of infection and eventually died. In contrast at this time point no clinical manifestations were observed among C57-CD40L−/− mice infected with 1×107 CFU. Infection was subclinical in WT mice inoculated with either bacterial dose. The serum samples from infected mice (1×107 CFU, collected at day 14 after infection, had similar C. rodentium-specific IgM titres. Although C57-CD40L−/− animals had lower IgG and IgG2b titres than WT mice, C57-CD40L−/− mice sera displayed complement-mediated bactericidal activity against C. rodentium. C. rodentium-infected C57-CD40L−/− mice are capable of producing antibodies that are protective. C57-CD40L−/− mouse is a useful surrogate model of X-HIGM syndrome for studying immune responses elicited against pathogens.

  11. Boosting of HIV-1 neutralizing antibody responses by a distally related retroviral envelope protein

    DEFF Research Database (Denmark)

    Uchtenhagen, Hannes; Schiffner, Torben; Bowles, Emma

    2014-01-01

    Our knowledge of the binding sites for neutralizing Abs (NAb) that recognize a broad range of HIV-1 strains (bNAb) has substantially increased in recent years. However, gaps remain in our understanding of how to focus B cell responses to vulnerable conserved sites within the HIV-1 envelope glycop...

  12. GRBs as Probes of the IGM

    CERN Document Server

    Cucchiara, A; Tanvir, N R

    2016-01-01

    Gamma-ray Bursts (GRBs) are the most powerful explosions known, capable of outshining the rest of gamma-ray sky during their short-lived prompt emission. Their cosmological nature makes them the best tool to explore the final stages in the lives of very massive stars up to the highest redshifts. Furthermore, studying the emission from their low-energy counterparts (optical and infrared) via rapid spectroscopy, we have been able to pin down the exact location of the most distant galaxies as well as placing stringent constraints on their host galaxies and intervening systems at low and high-redshift (e.g. metallicity and neutral hydrogen fraction). In fact, each GRB spectrum contains absorption features imprinted by metals in the host interstellar medium (ISM) as well as the intervening intergalactic medium (IGM) along the line of sight. In this chapter we summarize the progress made using a large dataset of GRB spectra in understanding the nature of both these absorbers and how GRBs can be used to study the ea...

  13. Broadly Neutralizing Antibodies against HIV-1 As a Novel Aspect of the Immune Response.

    Science.gov (United States)

    Shcherbakov, D N; Bakulina, A Y; Karpenko, L I; Ilyichev, A A

    2015-01-01

    The human immunodeficiency virus-1 (HIV-1) has the ability to evade the adaptive immune response due to high mutation rates. Soon after the discovery of HIV-1, it was originally proposed that neutralizing of antibodies to the virus occurs rarely or cannot be elicited at all. In the 1990s, there appeared reports that sera of select HIV-1-infected individuals contained antibodies capable of neutralizing different virus subtypes. Such antibodies were named broadly neutralizing antibodies (bNAbs). Since 2009, the development of new cell technologies has intensified research efforts directed at identifying new bNAbs with a neutralization potency of over 90% of primary HIV-1 isolates. These antibodies have unique characteristics which include high levels of somatic mutations and unusually long variable loops that penetrate through the glycan shield of HIV-1 Env to contact the protein surface. In this review, we will attempt to summarize the latest data on bNAbs against HIV-1 in terms of their interactions with the sites of vulnerability on HIV-1 glycoproteins.

  14. Tetravalent neutralizing antibody response against four dengue serotypes by a single chimeric dengue envelope antigen.

    Science.gov (United States)

    Apt, Doris; Raviprakash, Kanakatte; Brinkman, Alice; Semyonov, Andrey; Yang, Shumin; Skinner, Craig; Diehl, Lori; Lyons, Richard; Porter, Kevin; Punnonen, Juha

    2006-01-16

    We employed DNA shuffling and screening technologies to develop a single recombinant dengue envelope (E) antigen capable of inducing neutralizing antibodies against all four antigenically distinct dengue serotypes. By DNA shuffling of codon-optimized dengue 1-4 E genes, we created a panel of novel chimeric clones expressing C-terminal truncated E antigens that combined epitopes from all four dengue serotypes. DNA vaccines encoding these novel chimeras induced multivalent T cell and neutralizing antibody responses against all four dengue serotypes in mice. By contrast, a mixture of four unshuffled, parental DNA vaccines failed to produce tetravalent neutralizing antibodies in mice. The neutralizing antibody titers for some of these antigens could be further improved by extending the sequences to express full-length pre-membrane and envelope proteins. The chimeric antigens also protected mice against a lethal dengue-2 virus challenge. These data demonstrate that DNA shuffling and associated screening can lead to the selection of multi-epitope antigens against closely related dengue virus serotypes and suggest a broad utility for these technologies in optimizing vaccine antigens.

  15. Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting.

    Science.gov (United States)

    Doria-Rose, Nicole A; Altae-Tran, Han R; Roark, Ryan S; Schmidt, Stephen D; Sutton, Matthew S; Louder, Mark K; Chuang, Gwo-Yu; Bailer, Robert T; Cortez, Valerie; Kong, Rui; McKee, Krisha; O'Dell, Sijy; Wang, Felicia; Abdool Karim, Salim S; Binley, James M; Connors, Mark; Haynes, Barton F; Martin, Malcolm A; Montefiori, David C; Morris, Lynn; Overbaugh, Julie; Kwong, Peter D; Mascola, John R; Georgiev, Ivelin S

    2017-01-01

    Computational neutralization fingerprinting, NFP, is an efficient and accurate method for predicting the epitope specificities of polyclonal antibody responses to HIV-1 infection. Here, we present next-generation NFP algorithms that substantially improve prediction accuracy for individual donors and enable serologic analysis for entire cohorts. Specifically, we developed algorithms for: (a) selection of optimized virus neutralization panels for NFP analysis, (b) estimation of NFP prediction confidence for each serum sample, and (c) identification of sera with potentially novel epitope specificities. At the individual donor level, the next-generation NFP algorithms particularly improved the ability to detect multiple epitope specificities in a sample, as confirmed both for computationally simulated polyclonal sera and for samples from HIV-infected donors. Specifically, the next-generation NFP algorithms detected multiple specificities in twice as many samples of simulated sera. Further, unlike the first-generation NFP, the new algorithms were able to detect both of the previously confirmed antibody specificities, VRC01-like and PG9-like, in donor CHAVI 0219. At the cohort level, analysis of ~150 broadly neutralizing HIV-infected donor samples suggested a potential connection between clade of infection and types of elicited epitope specificities. Most notably, while 10E8-like antibodies were observed in infections from different clades, an enrichment of such antibodies was predicted for clade B samples. Ultimately, such large-scale analyses of antibody responses to HIV-1 infection can help guide the design of epitope-specific vaccines that are tailored to take into account the prevalence of infecting clades within a specific geographic region. Overall, the next-generation NFP technology will be an important tool for the analysis of broadly neutralizing polyclonal antibody responses against HIV-1.

  16. Ideological reactivity: Political conservatism and brain responsivity to emotional and neutral stimuli.

    Science.gov (United States)

    Tritt, Shona M; Peterson, Jordan B; Page-Gould, Elizabeth; Inzlicht, Michael

    2016-12-01

    Conservatives are often thought to have a negativity bias-responding more intensely to negative than positive information. Yet, recent research has found that greater endorsement of conservative beliefs follows from both positive and negative emotion inductions. This suggests that the role of affect in political thought may not be restricted to negative valence, and more attention should be given to how conservatives and liberals respond to a wider range of stimulation. In this vein, we examined neural responses to a full range of affective stimuli, allowing us to examine how self-reported ideology moderated these responses. Specifically, we explored the relationship between political orientation and 2 event-related potentials (1 late and 1 early) previously shown to covary with the subjective motivational salience of stimuli-in response to photographs with standardized ratings of arousal and valence. At late time points, conservatives exhibited sustained heightened reactivity, compared with liberals, specifically in response to relatively unarousing and neutral stimuli. At early time points, conservatives exhibited somewhat enhanced neural activity in response to all stimulus types compared with liberals. These results may suggest that conservatives experience a wide variety of stimuli in their environment with increased motivational salience, including positive, neutral, and low-arousal stimuli. No effects of valence were found in this investigation. Such findings have implications for the development and refinement of psychological conceptions of political orientation. (PsycINFO Database Record

  17. Whole Body Inhalation Exposure to 1-Bromopropane Suppresses the IgM Response to Sheep Red Blood Cells in Female B6C3F1 Mice and Fisher 344/N Rats

    Science.gov (United States)

    Anderson, Stacey. E.; Munson, Albert E.; Butterworth, Leon F.; Germolec, Dori; Morgan, Daniel L.; Roycroft, Joseph A.; Dill, Jeffrey; Meade, B. J.

    2010-01-01

    1-Bromopropane (1-BP) is categorized as a high-production volume chemical currently used in the manufacture of pharmaceuticals, pesticides and other chemicals. Its usage is estimated to be around 5 million pounds/year resulting in the potential for widespread exposure in the workplace. Case reports and animal studies have suggested exposure to this compound may cause adverse reproductive and neurological effects. Using a battery of immunological assays, the immunotoxicity of 1-BP after whole body inhalation exposure in both mice and rats was evaluated. Significant decreases in the spleen IgM response to SRBC were observed in both mice (125-500 ppm) and rats (1000 ppm) after exposure to 1-BP for 10 weeks. In addition, total spleen cells and T-cells were significantly decreased after approximately 4 weeks of 1-BP exposure in both mice (125-500 ppm) and rats (1000 ppm). No change in natural killer (NK) cell activity was observed. The observed alterations in spleen cellularity, phenotypic subsets and impairment of humoral immune function across species, raises further concern about human exposure to 1-BP and demonstrates the need for additional investigations into potential adverse health effects. PMID:20041805

  18. IgM nephropathy revisited.

    Science.gov (United States)

    Mubarak, Muhammed; Kazi, Javed I

    2012-01-01

    IgM nephropathy (IgMN) is an idiopathic immune complex-mediated glomerulopathy that was first described as a distinct disease in a nephropathology literature in 1978. Here, a historical review and the current status of IgMN in the light of world literature and the current experience will be presented. The Pubmed (www.pubmed.gov) search was made for articles on IgMN as the sole subject of the study or where it constituted a significant number of cases in a biopsy series in the world literature written in English. A total of 41 articles were found. A critical review of the literature was made. Soon after 1978, a series of reports were published mostly from the western world, but the interest in the entity did not withstand the test of time. No substantial basic medical research was carried out and the disease was largely ignored by the western researchers. More recently, a flurry of articles have appeared in the literature on the topic, mostly from tropical countries, and have renewed the interest in the entity. However, most of the current literature on IgMN is based on clinical observations, and experimental models and mechanistic studies of IgMN are lacking. There is an urgent need to develop consensus based criteria for the diagnosis of the condition, as well as, to focus the research on mechanistic studies to understand the pathogenesis of the disease better.

  19. The in vivo effects of neutralizing antibodies against IFN-γ, IL-4, or IL-10 on the humoral immune response in young and aged mice

    NARCIS (Netherlands)

    Dobber, R.; Tielemans, M.; Nagelkerken, L.

    1995-01-01

    In the present study we investigated whether age-related changes in the composition and functional properties of murine CD4+ T cells are reflected in vivo by a changed humoral response to influenza vaccine in aged mice. After the primary immunization, the titers of influenza-specific IgM, IgG1, IgG2

  20. HIV-1 subtype C superinfected individuals mount low autologous neutralizing antibody responses prior to intrasubtype superinfection

    Directory of Open Access Journals (Sweden)

    Basu Debby

    2012-09-01

    Full Text Available Abstract Background The potential role of antibodies in protection against intra-subtype HIV-1 superinfection remains to be understood. We compared the early neutralizing antibody (NAb responses in three individuals, who were superinfected within one year of primary infection, to ten matched non-superinfected controls from a Zambian cohort of subtype C transmission cases. Sequence analysis of single genome amplified full-length envs from a previous study showed limited diversification in the individuals who became superinfected with the same HIV-1 subtype within year one post-seroconversion. We hypothesized that this reflected a blunted NAb response, which may have made these individuals more susceptible to superinfection. Results Neutralization assays showed that autologous plasma NAb responses to the earliest, and in some cases transmitted/founder, virus were delayed and had low to undetectable titers in all three superinfected individuals prior to superinfection. In contrast, NAbs with a median IC50 titer of 1896 were detected as early as three months post-seroconversion in non-superinfected controls. Early plasma NAbs in all subjects showed limited but variable levels of heterologous neutralization breadth. Superinfected individuals also exhibited a trend toward lower levels of gp120- and V1V2-specific IgG binding antibodies but higher gp120-specific plasma IgA binding antibodies. Conclusions These data suggest that the lack of development of IgG antibodies, as reflected in autologous NAbs as well as gp120 and V1V2 binding antibodies to the primary infection virus, combined with potentially competing, non-protective IgA antibodies, may increase susceptibility to superinfection in the context of settings where a single HIV-1 subtype predominates.

  1. Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals.

    Directory of Open Access Journals (Sweden)

    Davide Corti

    Full Text Available BACKGROUND: The isolation of human monoclonal antibodies (mAbs that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. METHODS AND FINDINGS: We immortalized IgG(+ memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent. Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env in multiple parallel assays. We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity. One mAb in particular (HJ16 specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12. A second mAb (HGN194 bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third mAb (HK20 with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity. CONCLUSIONS: This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design.

  2. Correspondence of Neutralizing Humoral Immunity and CD4 T Cell Responses in Long Recovered Sudan Virus Survivors

    Directory of Open Access Journals (Sweden)

    Ariel Sobarzo

    2016-05-01

    Full Text Available Robust humoral and cellular immunity are critical for survival in humans during an ebolavirus infection. However, the interplay between these two arms of immunity is poorly understood. To address this, we examined residual immune responses in survivors of the Sudan virus (SUDV outbreak in Gulu, Uganda (2000–2001. Cytokine and chemokine expression levels in SUDV stimulated whole blood cultures were assessed by multiplex ELISA and flow cytometry. Antibody and corresponding neutralization titers were also determined. Flow cytometry and multiplex ELISA results demonstrated significantly higher levels of cytokine and chemokine responses in survivors with serological neutralizing activity. This correspondence was not detected in survivors with serum reactivity to SUDV but without neutralization activity. This previously undefined relationship between memory CD4 T cell responses and serological neutralizing capacity in SUDV survivors is key for understanding long lasting immunity in survivors of filovirus infections.

  3. Electromagnetic and neutral-weak response functions of 4He and 12C

    CERN Document Server

    Lovato, A; Carlson, J; Pieper, Steven C; Schiavilla, R

    2015-01-01

    Ab initio calculations of the quasi-elastic electromagnetic and neutral-weak response functions of 4He and 12C are carried out for the first time. They are based on a realistic approach to nuclear dynamics, in which the strong interactions are described by two- and three-nucleon potentials and the electroweak interactions with external fields include one- and two-body terms. The Green's function Monte Carlo method is used to calculate directly the Laplace transforms of the response functions, and maximum-entropy techniques are employed to invert the resulting imaginary-time correlation functions with associated statistical errors. The theoretical results, confirmed by experiment in the electromagnetic case, show that two-body currents generate excess transverse strength from threshold to the quasi-elastic to the dip region and beyond. These findings challenge the conventional picture of quasi-elastic inclusive scattering as being largely dominated by single-nucleon knockout processes.

  4. Engineering the vaccinia virus L1 protein for increased neutralizing antibody response after DNA immunization

    Directory of Open Access Journals (Sweden)

    Moss Bernard

    2009-03-01

    Full Text Available Abstract Background The licensed smallpox vaccine, comprised of infectious vaccinia virus, has associated adverse effects, particularly for immunocompromised individuals. Therefore, safer DNA and protein vaccines are being investigated. The L1 protein, a component of the mature virion membrane that is conserved in all sequenced poxviruses, is required for vaccinia virus entry into host cells and is a target for neutralizing antibody. When expressed by vaccinia virus, the unglycosylated, myristoylated L1 protein attaches to the viral membrane via a C-terminal transmembrane anchor without traversing the secretory pathway. The purpose of the present study was to investigate modifications of the gene expressing the L1 protein that would increase immunogenicity in mice when delivered by a gene gun. Results The L1 gene was codon modified for optimal expression in mammalian cells and potential N-glycosylation sites removed. Addition of a signal sequence to the N-terminus of L1 increased cell surface expression as shown by confocal microscopy and flow cytometry of transfected cells. Removal of the transmembrane domain led to secretion of L1 into the medium. Induction of binding and neutralizing antibodies in mice was enhanced by gene gun delivery of L1 containing the signal sequence with or without the transmembrane domain. Each L1 construct partially protected mice against weight loss caused by intranasal administration of vaccinia virus. Conclusion Modifications of the vaccinia virus L1 gene including codon optimization and addition of a signal sequence with or without deletion of the transmembrane domain can enhance the neutralizing antibody response of a DNA vaccine.

  5. IgM nephropathy; can we still ignore it.

    Science.gov (United States)

    Vanikar, Aruna

    2013-04-01

    IgM nephropathy (IgMN) is a relatively less recognized clinico-immunopathological entity in the domain of glomerulonephritis , often thought to be a bridge between minimal change disease and focal segmental glomerulosclerosis. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science has been searched. IgM nephropathy can present as nephritic syndrome or less commonly with subnephrotic proteinuria or rarely hematuria. About 30% patients respond to steroids whereas others are steroid dependent / resistant. They should be given a trial of Rituximab or stem cell therapy. IgM nephropathy (IgMN) is an important and rather neglected pathology responsible for renal morbidity in children and adults in developing countries as compared to developed nations with incidence of 2-18.5% of native biopsies. Abnormal T-cell function with hyperfunctioning suppressor T-cells are believed to be responsible for this disease entity. Approximately one third of the patients are steroid responders where as the remaining two thirds are steroid resistant or dependent. Therapeutic trials including cell therapies targeting suppressor T-cells are required.

  6. HIV-1 superinfection in women broadens and strengthens the neutralizing antibody response.

    Directory of Open Access Journals (Sweden)

    Valerie Cortez

    Full Text Available Identifying naturally-occurring neutralizing antibodies (NAb that are cross-reactive against all global subtypes of HIV-1 is an important step toward the development of a vaccine. Establishing the host and viral determinants for eliciting such broadly NAbs is also critical for immunogen design. NAb breadth has previously been shown to be positively associated with viral diversity. Therefore, we hypothesized that superinfected individuals develop a broad NAb response as a result of increased antigenic stimulation by two distinct viruses. To test this hypothesis, plasma samples from 12 superinfected women each assigned to three singly infected women were tested against a panel of eight viruses representing four different HIV-1 subtypes at matched time points post-superinfection (~5 years post-initial infection. Here we show superinfected individuals develop significantly broader NAb responses post-superinfection when compared to singly infected individuals (RR = 1.68, CI: 1.23-2.30, p = 0.001. This was true even after controlling for NAb breadth developed prior to superinfection, contemporaneous CD4+ T cell count and viral load. Similarly, both unadjusted and adjusted analyses showed significantly greater potency in superinfected cases compared to controls. Notably, two superinfected individuals were able to neutralize variants from four different subtypes at plasma dilutions >1∶300, suggesting that their NAbs exhibit elite activity. Cross-subtype breadth was detected within a year of superinfection in both of these individuals, which was within 1.5 years of their initial infection. These data suggest that sequential infections lead to augmentation of the NAb response, a process that may provide insight into potential mechanisms that contribute to the development of antibody breadth. Therefore, a successful vaccination strategy that mimics superinfection may lead to the development of broad NAbs in immunized individuals.

  7. In vitro neutralization of viral hemorrhagic septicemia virus by plasma from immunized zebrafish.

    Science.gov (United States)

    Chinchilla, Blanca; Gomez-Casado, Eduardo; Encinas, Paloma; Falco, Alberto; Estepa, Amparo; Coll, Julio

    2013-03-01

    We studied humoral long-term adaptive viral neutralization responses in zebrafish (Danio rerio), an increasingly useful vertebrate model for viral diseases actually limited by the absence of standardized anti-zebrafish immunoglobulin M (IgM) antibodies. We established an alternative method, similar to those used in other fish, to achieve a first estimation of zebrafish anti-viral antibody-like responses. We used the viral hemorrhagic septicemia virus (VHSV) model because, although protection after this non-natural infection was demonstrated in cold-acclimatized zebrafish, little is known about their induced anti-VHSV antibody-like responses. Therefore, we first optimized a micro-neutralization method based on immunostaining VHSV-infected fish cell monolayers to detect zebrafish neutralizing activity in plasma samples in one day. We then used the method to measure the specific anti-VHSV neutralization in plasma obtained from individual zebrafish under various VHSV challenges or immunization protocols. The neutralizing activity was inhibited by protein A-sepharose and rabbit anti-zebrafish IgM antibodies, suggesting the implication of IgM zebrafish antibodies in such responses. To our knowledge, this is the first report to demonstrate detectable and significant VHSV neutralization titers in zebrafish surviving VHSV infections. This micro-method might be useful, not only for the follow-up of infection/vaccine development in the zebrafish/VHSV model in particular, but also for similar work involving other in vitro neutralizable zebrafish pathogens. This technique might also further the development of alternative ELISA assay methods to measure specific immunoglobulins in zebrafish.

  8. Heart Rate Responses to Unaided Orion Side Hatch Egress in the Neutral Buoyancy Laboratory

    Science.gov (United States)

    English, Kirk L.; Hwang, Emma Y.; Ryder, Jeffrey W.; Kelly, Cody; Walker, Thomas; Ploutz-Snyder, Lori

    2016-01-01

    The Orion capsule will be the next NASA-built vehicle used for near and deep space exploration. The nominal landing scenario for Orion involves splashdown in the Pacific Ocean and subsequent aided crew egress conducted by military personnel. Contingency operations, however, require the crew to egress the capsule unaided, deploy an inflatable life raft, and to ingress the raft. Unaided egress is expected to be physiologically demanding, but no data exist to corroborate this. Thus, we evaluated the heart rate response to unaided Orion side hatch egress and raft ingress as par of the NASA crew Survival Engineering Team's evaluation of egress procedures using the Post-landing Orion Recovery Trainer (PORT) article in the Neutral Buoyancy Laboratory (NBL).

  9. Boosting of HIV-1 neutralizing antibody responses by a distally related retroviral envelope protein.

    Science.gov (United States)

    Uchtenhagen, Hannes; Schiffner, Torben; Bowles, Emma; Heyndrickx, Leo; LaBranche, Celia; Applequist, Steven E; Jansson, Marianne; De Silva, Thushan; Back, Jaap Willem; Achour, Adnane; Scarlatti, Gabriella; Fomsgaard, Anders; Montefiori, David; Stewart-Jones, Guillaume; Spetz, Anna-Lena

    2014-06-15

    Our knowledge of the binding sites for neutralizing Abs (NAb) that recognize a broad range of HIV-1 strains (bNAb) has substantially increased in recent years. However, gaps remain in our understanding of how to focus B cell responses to vulnerable conserved sites within the HIV-1 envelope glycoprotein (Env). In this article, we report an immunization strategy composed of a trivalent HIV-1 (clade B envs) DNA prime, followed by a SIVmac239 gp140 Env protein boost that aimed to focus the immune response to structurally conserved parts of the HIV-1 and simian immunodeficiency virus (SIV) Envs. Heterologous NAb titers, primarily to tier 1 HIV-1 isolates, elicited during the trivalent HIV-1 env prime, were significantly increased by the SIVmac239 gp140 protein boost in rabbits. Epitope mapping of Ab-binding reactivity revealed preferential recognition of the C1, C2, V2, V3, and V5 regions. These results provide a proof of concept that a distally related retroviral SIV Env protein boost can increase pre-existing NAb responses against HIV-1.

  10. Neutralizing antibody response in the patients with hand, foot and mouth disease to enterovirus 71 and its clinical implications

    Directory of Open Access Journals (Sweden)

    Zhu Liye

    2011-06-01

    Full Text Available Abstract Enterovirus 71 (EV71 has emerged as a significant pathogen causing large outbreaks in China for the past 3 years. Developing an EV71 vaccine is urgently needed to stop the spread of the disease; however, the adaptive immune response of humans to EV71 infection remains unclear. We examined the neutralizing antibody titers in HFMD patients and compared them to those of asymptomatic healthy children and young adults. We found that 80% of HFMD patients became positive for neutralizing antibodies against EV71 (GMT = 24.3 one day after the onset of illness. The antibody titers in the patients peaked two days (GMT = 79.5 after the illness appeared and were comparable to the level of adults (GMT = 45.2. Noticeably, the antibody response was not correlated with disease severity, suggesting that cellular immune response, besides neutralizing antibodies, could play critical role in controlling the outcome of EV71 infection in humans.

  11. Functional Differences between IgM and IgD Signaling in Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Ten Hacken, Elisa; Sivina, Mariela; Kim, Ekaterina; O'Brien, Susan; Wierda, William G; Ferrajoli, Alessandra; Estrov, Zeev; Keating, Michael J; Oellerich, Thomas; Scielzo, Cristina; Ghia, Paolo; Caligaris-Cappio, Federico; Burger, Jan A

    2016-09-15

    BCR signaling is a central pathogenetic pathway in chronic lymphocytic leukemia (CLL). Most CLL cells express BCRs of IgM and IgD isotypes, but the contribution of these isotypes to functional responses remains incompletely defined. We therefore investigated differences between IgM and IgD signaling in freshly isolated peripheral blood CLL cells and in CLL cells cultured with nurselike cells, a model that mimics the lymph node microenvironment. IgM signaling induced prolonged activation of ERK kinases and promoted CLL cell survival, CCL3 and CCL4 chemokine secretion, and downregulation of BCL6, the transcriptional repressor of CCL3 In contrast, IgD signaling induced activation of the cytoskeletal protein HS1, along with F-actin polymerization, which resulted in rapid receptor internalization and failure to support downstream responses, including CLL cell survival and chemokine secretion. IgM and IgD receptor downmodulation, HS1 and ERK activation, chemokine secretion, and BCL6 downregulation were also observed when CLL cells were cocultured with nurselike cells. The Bruton's tyrosine kinase inhibitor ibrutinib effectively inhibited both IgM and IgD isotype signaling. In conclusion, through a variety of functional readouts, we demonstrate very distinct outcomes of IgM and IgD isotype activation in CLL cells, providing novel insight into the regulation of BCR signaling in CLL.

  12. Recognition of Porphyromonas gingivalis gingipain epitopes by natural IgM binding to malondialdehyde modified low-density lipoprotein.

    Directory of Open Access Journals (Sweden)

    S Pauliina Turunen

    Full Text Available OBJECTIVE: Increased risk for atherosclerosis is associated with infectious diseases including periodontitis. Natural IgM antibodies recognize pathogen-associated molecular patterns on bacteria, and oxidized lipid and protein epitopes on low-density lipoprotein (LDL and apoptotic cells. We aimed to identify epitopes on periodontal pathogen Porphyromonas gingivalis recognized by natural IgM binding to malondialdehyde (MDA modified LDL. METHODS AND RESULTS: Mouse monoclonal IgM (MDmAb specific for MDA-LDL recognized epitopes on P. gingivalis on flow cytometry and chemiluminescence immunoassays. Immunization of C57BL/6 mice with P. gingivalis induced IgM, but not IgG, immune response to MDA-LDL and apoptotic cells. Immunization of LDLR(-/- mice with P. gingivalis induced IgM, but not IgG, immune response to MDA-LDL and diminished aortic lipid deposition. On Western blot MDmAb bound to P. gingivalis fragments identified as arginine-specific gingipain (Rgp by mass spectrometry. Recombinant domains of Rgp produced in E. coli were devoid of phosphocholine epitopes but contained epitopes recognized by MDmAb and human serum IgM. Serum IgM levels to P. gingivalis were associated with anti-MDA-LDL levels in humans. CONCLUSION: Gingipain of P. gingivalis is recognized by natural IgM and shares molecular identity with epitopes on MDA-LDL. These findings suggest a role for natural antibodies in the pathogenesis of two related inflammatory diseases, atherosclerosis and periodontitis.

  13. The Great War and Dutch Contract Law : Resistance, Responsiveness and Neutrality

    NARCIS (Netherlands)

    Boom, van W.H.

    2014-01-01

    Throughout the Great War, the Netherlands tried frantically to remain a neutral nation between the warring Central Powers and the Entente Forces. Notwithstanding its neutrality, the war left distinct marks on Dutch society and economy. This article argues that it also left marks, both temporary and

  14. The Great War and Dutch Contract Law : Resistance, Responsiveness and Neutrality

    NARCIS (Netherlands)

    Boom, van W.H.

    2014-01-01

    Throughout the Great War, the Netherlands tried frantically to remain a neutral nation between the warring Central Powers and the Entente Forces. Notwithstanding its neutrality, the war left distinct marks on Dutch society and economy. This article argues that it also left marks, both temporary and

  15. Neither state or trait anxiety alter the response to distracting emotionally neutral sounds.

    Science.gov (United States)

    Hoskin, Robert; Hunter, Mike D; Woodruff, Peter W R

    2015-01-01

    Attentional control theory suggests that heightened anxiety, whether due to trait or state factors, causes an increased vulnerability to distraction even when the distracters are emotionally neutral. Recent passive oddball studies appear to support this theory in relation to the distraction caused by emotionally neutral sounds. However such studies have manipulated emotional state via the content of task stimuli, thus potentially confounding changes in emotion with differences in task demands. To identify the effect of anxiety on the distraction caused by emotionally neutral sounds, 50 participants completed a passive oddball task requiring emotionally neutral sounds to be ignored. Crucially, state anxiety was manipulated independent of the task stimuli (via unrelated audiovisual stimuli) thus removing confounds relating to task demands. Neither state or trait anxiety was found to influence the susceptibility to distraction by emotionally neutral sounds. These findings contribute to the ongoing debate concerning the impact of emotion on attention.

  16. Global and Meso-scale Thermospheric Neutral Wind Response to Geomagnetic Storm

    Science.gov (United States)

    Lu, G.; Conde, M.; Doornbos, E.

    2015-12-01

    This paper presents a case study of thermospheric response to the 5 April 2010 geomagnetic storm. The NCAR Thermosphere-Ionosphere-Mesosphere Electrodynamic General Circulation Model (TIMEGCM) is used to investigate thermospheric neutral wind variations during the storm, and the model results are validated through comparison with ground and space based observations. More specifically, we conduct detailed inter-comparison of the winds observed by scanning Doppler imagers (SDI) in Alaska with those derived from the TIMEGCM simulations in order to assess model's ability in reproducing the observed meso-scale wind field. The thermospheric winds obtained from the accelerometers on board the GOCE satellite are also used to validate the simulation results on a global scale. While globally the wind velocity tends to be smaller than ion drift velocity, locally the winds can exceed ion drifts and also blow in the different direction than the ions. We will discuss how the thermospheric winds affect the energetic coupling of the magnetosphere-ionosphere-thermosphere system in terms of Joule heating and field-aligned currents.

  17. Dose-response curve slope helps predict therapeutic potency and breadth of HIV broadly neutralizing antibodies.

    Science.gov (United States)

    Webb, Nicholas E; Montefiori, David C; Lee, Benhur

    2015-09-29

    A new generation of HIV broadly neutralizing antibodies (bnAbs) with remarkable potency, breadth and epitope diversity has rejuvenated interest in immunotherapeutic strategies. Potencies defined by in vitro IC50 and IC80 values (50 and 80% inhibitory concentrations) figure prominently into the selection of clinical candidates; however, much higher therapeutic levels will be required to reduce multiple logs of virus and impede escape. Here we predict bnAb potency at therapeutic levels by analysing dose-response curve slopes, and show that slope is independent of IC50/IC80 and specifically relates to bnAb epitope class. With few exceptions, CD4-binding site and V3-glycan bnAbs exhibit slopes >1, indicative of higher expected therapeutic effectiveness, whereas V2-glycan, gp41 membrane-proximal external region (MPER) and gp120-gp41 bnAbs exhibit less favourable slopes <1. Our results indicate that slope is one major predictor of both potency and breadth for bnAbs at clinically relevant concentrations, and may better coordinate the relationship between bnAb epitope structure and therapeutic expectations.

  18. Considering changing temporal structures in the construction of scenario-neutral runoff response surfaces

    Science.gov (United States)

    Vormoor, Klaus; Rössler, Ole; Bürger, Gerd; Weingartner, Rolf; Bronstert, Axel

    2016-04-01

    Climate change impact studies are usually based on traditional top-down approaches in which post-processed climate model data serves as input into some kind of impact model. Parallel to these traditional approaches, scenario-neutral bottom-up approaches have been developed as an alternative methodology which assesses the intrinsic vulnerability of a system towards climate change. Such bottom-approaches perform a sensitivity analysis of an impact model towards systematically 'user-defined' changes in the climate system and summarize its response in a two-dimensional matrix: the response surface. The climate change signal is obtained by perturbing observed time series, which serve as inputs into the impact models. The impact model is then run with all possible combinations of perturbed input data series and the result of each combination (i.e. the impact) is plotted as one single realization (i.e. one pixel) of possible climate change impacts over the two dimensional domain. Although the complexity of existing perturbation methods varies, the temporal structure (i.e. the seasonal- and day-to-day-variability) of these time series often remains the same, which is critical, in particular for the simulations of extremes. In this study, we present standardized response surfaces (SRS) that are based on impact simulations using both perturbed climate observations and projections which are scaled to a common domain. We apply this approach within the field of hydrology and estimate different aspects of runoff response, covering mean runoff as well as extremes like low flows and floods in a Nordic catchment with a mixed snowmelt/rainfall regime. Climate observations and projections from eight GCM-RCM combinations, downscaled by two different methods, are used for the perturbation which results in 17 different SRS. A series of linear regression- and linear mixed-effects models is applied to quantify the different effects of perturbing the climate input data and of the varying

  19. All eyes on the next generation of HIV vaccines: strategies for inducing a broadly neutralizing antibody response.

    Science.gov (United States)

    Ahlers, Jeffrey D

    2014-04-01

    HIV-1 broadly neutralizing antibodies (BNAbs) develop after several years of infection through a recursive process of memory B cell adaptation and maturation against co-evolving virus quasispecies. Advances in single-cell sorting and memory B cell antibody cloning methods have identified many new HIV BNAbs targeting conserved epitopes on the HIV envelope (env) protein. 3D crystal structures and biophysical analyses of BNAbs bound to invariant virus structures expressed on monomeric gp120, epitope scaffolds, core structures, and native trimers have helped us to visualize unique binding interactions and paratope orientations that have been instrumental in guiding vaccine design. A paradigm shift in the approach to structure-based design of HIV-1 envelope immunogens came recently after several laboratories discovered that native viral envelopes or "env-structures" reverse-engineered to bind with high affinity to a handful of broadly neutralizing antibodies did not in fact bind the predicted germline precursors of these broadly neutralizing antibodies. A major challenge for HIV-1 B cell vaccine development moving forward is the design of new envelope immunogens that can trigger the selection and expansion of germline precursor and intermediate memory B cells to recapitulate B cell ontogenies associated with the maturation of a broadly neutralizing antibody response. Equally important for vaccine development is the identification of delivery systems, prime-boost strategies, and synergistic adjuvant combinations that can induce the magnitude and quality of antigen-specific T follicular helper (TFH) cell responses needed to drive somatic hypermutation (SHM) and B cell maturation against heterologous primary virus envelopes. Finding the combination of multi-protein envelope immunogens and immunization strategies that can evolve a potent broadly neutralizing antibody response portends to require a complex vaccine regimen that might be difficult to implement on any scale

  20. Systemic lupus erythematosus patients contain significantly less igm against mono-methylated lysine than healthy subjects.

    Directory of Open Access Journals (Sweden)

    Sha Guo

    Full Text Available Post-translational modifications on proteins are important in biological processes but may create neo-epitopes that induce autoimmune responses. In this study, we measured the serum IgG and IgM response to a set of non-modified or acetyl- and methyl-modified peptides corresponding to residues 1-19 of the histone 3 N-terminal tail in systemic lupus erythematosus (SLE patients and healthy subjects. Our results indicated that the SLE patients and healthy subjects produced antibodies (Abs to the peptides, but the two groups had different Ab isotype and epitope preferences. Abs to the non-modified form, H31-19, were of the IgG isotype and produced by SLE patients. They could not recognize the scrambled H31-19, which contained the same amino acid composition but a different sequence as H31-19. In comparison, healthy subjects in general did not produce IgG against H31-19. However, about 70% of the healthy subjects produced IgM Abs against mono-methylated K9 of H31-19 (H31-19K9me. Our further studies revealed that ε-amine mono-methylated lysine could completely inhibit the IgM binding to H31-19K9me, but lysine had no inhibitory effect. In addition, the IgM Abs could bind peptides containing a mono-methylated lysine residue but with totally different sequences. Thus, mono-methylated lysine was the sole epitope for the IgM. Interestingly, SLE patients had much lower levels of this type of IgM. There was no obvious correlation between the IgM levels and disease activity and the decreased IgM was unlikely caused by medical treatments.We also found that the IgM Abs were not polyreactive to dsDNA, ssDNA, lipopolysaccharide (LPS or insulin and they did not exist in umbilical cord serum, implying that they were not natural Abs. The IgM Abs against mono-methylated lysine are present in healthy subjects but are significantly lower in SLE patients, suggesting a distinct origin of production and special physiological functions.

  1. Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins.

    Directory of Open Access Journals (Sweden)

    Gerald V Quinnan

    Full Text Available A major goal of efforts to develop a vaccine to prevent HIV-1 infection is induction of broadly cross-reactive neutralizing antibodies (bcnAb. In previous studies we have demonstrated induction of neutralizing antibodies that did cross-react among multiple primary and laboratory strains of HIV-1, but neutralized with limited potency. In the present study we tested the hypothesis that immunization with multiple HIV-1 envelope glycoproteins (Envs would result in a more potent and cross-reactive neutralizing response. One Env, CM243(N610Q, was selected on the basis of studies of the effects of single and multiple mutations of the four gp41 glycosylation sites. The other two Envs included R2 (subtype B and 14/00/4 (subtype F, both of which were obtained from donors with bcnAb. Rhesus monkeys were immunized using a prime boost regimen as in previous studies. Individual groups of monkeys were immunized with either one of the three Envs or all three. The single N610Q and N615Q mutations of CM243 Env did not disrupt protein secretion, processing into, or reactivity with mAbs, unlike other single or multiple deglycosylation mutations. In rabbit studies the N610Q mutation alone or in combination was associated with an enhanced neutralizing response against homologous and heterologous subtype E viruses. In the subsequent monkey study the response induced by the R2 Env regimen was equivalent to the trivalent regimen and superior to the other monovalent regimens against the virus panel used for testing. The 14/00/4 Env induced responses superior to CM243(N610Q. The results indicate that elimination of the glycosylation site near the gp41 loop results in enhanced immunogenicity, but that immunization of monkeys with these three distinct Envs was not more immunogenic than with one.

  2. ANTI M. leprae IgM ANTIBODY DETERMINATION BY ULTRAMICROIMMUNOENZYMATIC (UMELISA HANSEN FOR THE DIAGNOSIS AND MONITORING LEPROSY

    Directory of Open Access Journals (Sweden)

    Adriana TORRELLA

    1998-05-01

    Full Text Available The relationship between the IgM antibody response, antigenic load as well as the clinical improvement after chemotherapy was studied in order to obtain useful data for the early diagnosis and monitoring leprosy. A level of 82% (94/115 agreement was obtained between IgM UMELISA HANSEN and slitskin smear examination. Discrepant results were observed in 16 patients who showed positive IgM response despite negative by the skin smear examination. In these patients, the IgM response was seen to be associated to the early signal for bacilli recurrence in the skin. In one of these patients the presence of bacilli was demonstrated in the skin, two months after IgM antibodies being detected by UMELISA HANSEN. Also in one of the treated patients positive by both diagnostic techniques, a remarkable decrease in the IgM antibody levels was seen, correlating with a significant clinical improvement. Moreover it was found a direct relationship between the IgM antibody response and bacterial antigenic load, regardless the time elapsed in the disease's evolution.El UMELISA HANSEN en el diagnostico y seguimiento de la lepra. Se analizó la relación entre la carga antigénica y la respuesta de anticuerpos IgM, el comportamiento de dicha respuesta y la utilidad de su detección para el diagnóstico y seguimiento de la lepra. Se obtuvo un 82% de coincidencia entre los resultados del UMELISA HANSEN y los de la baciloscopía. Este valor se vio afectado fundamentalmente por 16 pacientes con respuesta positiva a IgM y baciloscopía negativa. En estos pacientes de acuerdo a lo reportado, la respuesta IgM puede indicar la reaparición de bacilos, precediendo a su detección en la piel. En uno de estos pacientes se demostró la presencia de bacilos, dos meses después de resultar positivo por el UMELISA HANSEN. Entre los pacientes coincidentes en IgM y baciloscopía positivas con tratamiento quimioterapéutico, se apreció en uno de ellos una notable disminución en los

  3. IGM metal enrichment through dust sputtering

    CERN Document Server

    Bianchi, S; Bianchi, Simone; Ferrara, Andrea

    2005-01-01

    We study the motion of dust grains into the Intergalactic Medium (IGM) around redshift z=3, to test the hypothesis that grains can efficiently pollute the gas with metals through sputtering. We use the results available in the literature for radiation-driven dust ejection from galaxies as initial conditions, and follow the motion onward. Via this mechanism, grains are ejected into the IGM with velocities >100 km/s; as they move supersonically, grains can be efficiently eroded by non-thermal sputtering. However, Coulomb and collisional drag forces effectively reduce the charged grain velocity. Up-to-date sputtering yields for graphite and silicate (olivine) grains have been derived using the code TRIM, for which we provide analytic fits. After training our method on a homogeneous density case, we analyze the grain motion and sputtering in the IGM density field as derived from a LambdaCDM cosmological simulation at z = 3.27. We found that only large (a >~ 0.1-um) grains can travel up to considerable distances (...

  4. Reactions to facial expressions: effects of social context and speech anxiety on responses to neutral, anger, and joy expressions.

    Science.gov (United States)

    Vrana, Scott R; Gross, Daniel

    2004-03-01

    Male and female participants (n=19) high or low in speech fear viewed pictures of faces posed in anger, neutral, and joyful expressions for 8s each. Zygomaticus major and corrugator supercilii EMG, skin conductance, and heart rate were measured during picture viewing, and subjective ratings were made after each picture. Compared to anger expressions, joy expressions were responded to with greater zygomatic EMG, less corrugator EMG, and greater heart rate and skin conductance. Physiological response to neutral expressions was similar to response to anger expressions. Expressions posed by women were responded to physiologically more negatively than expressions posed by men. More fearful participants exhibited more negative and less positive facial expressions, and skin conductance responses suggesting greater attention when viewing negative expressions. Results suggest that reactions to facial expressions are influenced by social context, and are not simple mimicry.

  5. Precisely Molded Nanoparticle Displaying DENV-E Proteins Induces Robust Serotype-Specific Neutralizing Antibody Responses.

    Directory of Open Access Journals (Sweden)

    Stefan W Metz

    2016-10-01

    Full Text Available Dengue virus (DENV is the causative agent of dengue fever and dengue hemorrhagic fever. The virus is endemic in over 120 countries, causing over 350 million infections per year. Dengue vaccine development is challenging because of the need to induce simultaneous protection against four antigenically distinct DENV serotypes and evidence that, under some conditions, vaccination can enhance disease due to specific immunity to the virus. While several live-attenuated tetravalent dengue virus vaccines display partial efficacy, it has been challenging to induce balanced protective immunity to all 4 serotypes. Instead of using whole-virus formulations, we are exploring the potentials for a particulate subunit vaccine, based on DENV E-protein displayed on nanoparticles that have been precisely molded using Particle Replication in Non-wetting Template (PRINT technology. Here we describe immunization studies with a DENV2-nanoparticle vaccine candidate. The ectodomain of DENV2-E protein was expressed as a secreted recombinant protein (sRecE, purified and adsorbed to poly (lactic-co-glycolic acid (PLGA nanoparticles of different sizes and shape. We show that PRINT nanoparticle adsorbed sRecE without any adjuvant induces higher IgG titers and a more potent DENV2-specific neutralizing antibody response compared to the soluble sRecE protein alone. Antigen trafficking indicate that PRINT nanoparticle display of sRecE prolongs the bio-availability of the antigen in the draining lymph nodes by creating an antigen depot. Our results demonstrate that PRINT nanoparticles are a promising platform for delivering subunit vaccines against flaviviruses such as dengue and Zika.

  6. The Limits of Corporate Social Responsibility: Techniques of Neutralization, Stakeholder Management and Political CSR.

    Science.gov (United States)

    Fooks, Gary; Gilmore, Anna; Collin, Jeff; Holden, Chris; Lee, Kelley

    2013-01-01

    Since scholarly interest in corporate social responsibility (CSR) has primarily focused on the synergies between social and economic performance, our understanding of how (and the conditions under which) companies use CSR to produce policy outcomes that work against public welfare has remained comparatively under-developed. In particular, little is known about how corporate decision-makers privately reconcile the conflicts between public and private interests, even though this is likely to be relevant to understanding the limitations of CSR as a means of aligning business activity with the broader public interest. This study addresses this issue using internal tobacco industry documents to explore British-American Tobacco's (BAT) thinking on CSR and its effects on the company's CSR Programme. The article presents a three-stage model of CSR development, based on Sykes and Matza's theory of techniques of neutralization, which links together: how BAT managers made sense of the company's declining political authority in the mid-1990s; how they subsequently justified the use of CSR as a tool of stakeholder management aimed at diffusing the political impact of public health advocates by breaking up political constituencies working towards evidence-based tobacco regulation; and how CSR works ideologically to shape stakeholders' perceptions of the relative merits of competing approaches to tobacco control. Our analysis has three implications for research and practice. First, it underlines the importance of approaching corporate managers' public comments on CSR critically and situating them in their economic, political and historical contexts. Second, it illustrates the importance of focusing on the political aims and effects of CSR. Third, by showing how CSR practices are used to stymie evidence-based government regulation, the article underlines the importance of highlighting and developing matrices to assess the negative social impacts of CSR.

  7. Precisely Molded Nanoparticle Displaying DENV-E Proteins Induces Robust Serotype-Specific Neutralizing Antibody Responses

    Science.gov (United States)

    Hoekstra, Gabriel; Yi, Xianwen; Stone, Michelle; Horvath, Katie; Miley, Michael J.; DeSimone, Joseph; Luft, Chris J.; de Silva, Aravinda M.

    2016-01-01

    Dengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic fever. The virus is endemic in over 120 countries, causing over 350 million infections per year. Dengue vaccine development is challenging because of the need to induce simultaneous protection against four antigenically distinct DENV serotypes and evidence that, under some conditions, vaccination can enhance disease due to specific immunity to the virus. While several live-attenuated tetravalent dengue virus vaccines display partial efficacy, it has been challenging to induce balanced protective immunity to all 4 serotypes. Instead of using whole-virus formulations, we are exploring the potentials for a particulate subunit vaccine, based on DENV E-protein displayed on nanoparticles that have been precisely molded using Particle Replication in Non-wetting Template (PRINT) technology. Here we describe immunization studies with a DENV2-nanoparticle vaccine candidate. The ectodomain of DENV2-E protein was expressed as a secreted recombinant protein (sRecE), purified and adsorbed to poly (lactic-co-glycolic acid) (PLGA) nanoparticles of different sizes and shape. We show that PRINT nanoparticle adsorbed sRecE without any adjuvant induces higher IgG titers and a more potent DENV2-specific neutralizing antibody response compared to the soluble sRecE protein alone. Antigen trafficking indicate that PRINT nanoparticle display of sRecE prolongs the bio-availability of the antigen in the draining lymph nodes by creating an antigen depot. Our results demonstrate that PRINT nanoparticles are a promising platform for delivering subunit vaccines against flaviviruses such as dengue and Zika. PMID:27764114

  8. Transcriptomic and metabolomic profiling of chicken adipose tissue in response to insulin neutralization and fasting.

    Science.gov (United States)

    Ji, Bo; Ernest, Ben; Gooding, Jessica R; Das, Suchita; Saxton, Arnold M; Simon, Jean; Dupont, Joelle; Métayer-Coustard, Sonia; Campagna, Shawn R; Voy, Brynn H

    2012-08-31

    Domestic broiler chickens rapidly accumulate adipose tissue due to intensive genetic selection for rapid growth and are naturally hyperglycemic and insulin resistant, making them an attractive addition to the suite of rodent models used for studies of obesity and type 2 diabetes in humans. Furthermore, chicken adipose tissue is considered as poorly sensitive to insulin and lipolysis is under glucagon control. Excessive fat accumulation is also an economic and environmental concern for the broiler industry due to the loss of feed efficiency and excessive nitrogen wasting, as well as a negative trait for consumers who are increasingly conscious of dietary fat intake. Understanding the control of avian adipose tissue metabolism would both enhance the utility of chicken as a model organism for human obesity and insulin resistance and highlight new approaches to reduce fat deposition in commercial chickens. We combined transcriptomics and metabolomics to characterize the response of chicken adipose tissue to two energy manipulations, fasting and insulin deprivation in the fed state. Sixteen to 17 day-old commercial broiler chickens (ISA915) were fed ad libitum, fasted for five hours, or fed but deprived of insulin by injections of anti-insulin serum. Pair-wise contrasts of expression data identified a total of 2016 genes that were differentially expressed after correction for multiple testing, with the vast majority of differences due to fasting (1780 genes). Gene Ontology and KEGG pathway analyses indicated that a short term fast impacted expression of genes in a broad selection of pathways related to metabolism, signaling and adipogenesis. The effects of insulin neutralization largely overlapped with the response to fasting, but with more modest effects on adipose tissue metabolism. Tissue metabolomics indicated unique effects of insulin on amino acid metabolism. Collectively, these data provide a foundation for further study into the molecular basis for adipose

  9. Transcriptomic and metabolomic profiling of chicken adipose tissue in response to insulin neutralization and fasting

    Directory of Open Access Journals (Sweden)

    Ji Bo

    2012-08-01

    Full Text Available Abstract Background Domestic broiler chickens rapidly accumulate adipose tissue due to intensive genetic selection for rapid growth and are naturally hyperglycemic and insulin resistant, making them an attractive addition to the suite of rodent models used for studies of obesity and type 2 diabetes in humans. Furthermore, chicken adipose tissue is considered as poorly sensitive to insulin and lipolysis is under glucagon control. Excessive fat accumulation is also an economic and environmental concern for the broiler industry due to the loss of feed efficiency and excessive nitrogen wasting, as well as a negative trait for consumers who are increasingly conscious of dietary fat intake. Understanding the control of avian adipose tissue metabolism would both enhance the utility of chicken as a model organism for human obesity and insulin resistance and highlight new approaches to reduce fat deposition in commercial chickens. Results We combined transcriptomics and metabolomics to characterize the response of chicken adipose tissue to two energy manipulations, fasting and insulin deprivation in the fed state. Sixteen to 17 day-old commercial broiler chickens (ISA915 were fed ad libitum, fasted for five hours, or fed but deprived of insulin by injections of anti-insulin serum. Pair-wise contrasts of expression data identified a total of 2016 genes that were differentially expressed after correction for multiple testing, with the vast majority of differences due to fasting (1780 genes. Gene Ontology and KEGG pathway analyses indicated that a short term fast impacted expression of genes in a broad selection of pathways related to metabolism, signaling and adipogenesis. The effects of insulin neutralization largely overlapped with the response to fasting, but with more modest effects on adipose tissue metabolism. Tissue metabolomics indicated unique effects of insulin on amino acid metabolism. Conclusions Collectively, these data provide a foundation

  10. Probing the IGM with Ly$\\mathrm{\\alpha}$ and 21 cm fluctuations

    CERN Document Server

    Heneka, Caroline; Feng, Chang

    2016-01-01

    We study 21 cm and Ly$\\mathrm{\\alpha}$ fluctuations, as well as H$\\mathrm{\\alpha}$, while distinguishing for Ly$\\mathrm{\\alpha}$ between emission of galactic, diffuse and scattered IGM origin. Cross-correlation information about the state of the IGM is worked out, testing neutral versus ionized medium with different tracers in a semi-numerical simulation setup. In order to path the way for constraints on reionization history and modelling beyond power spectrum information, we explore parameter dependencies of the cross-power signal between 21$\\,$cm and Ly$\\mathrm{\\alpha}$, which displays characteristic morphology and a turn-over from negative to positive correlation at scales of a couple Mpc$^{-1}$. In a proof of concept for the extraction of further information on the state of the IGM using different tracers, we demonstrate the usage of the 21$\\,$cm and H$\\mathrm{\\alpha}$ cross-correlation signal to determine the relative strength of galactic and IGM emission in Ly$\\mathrm{\\alpha}$. We conclude by showing th...

  11. Heterosubtype neutralizing responses to influenza A (H5N1 viruses are mediated by antibodies to virus haemagglutinin.

    Directory of Open Access Journals (Sweden)

    Jean-Michel Garcia

    Full Text Available BACKGROUND: It is increasingly clear that influenza A infection induces cross-subtype neutralizing antibodies that may potentially confer protection against zoonotic infections. It is unclear whether this is mediated by antibodies to the neuraminidase (NA or haemagglutinin (HA. We use pseudoviral particles (H5pp coated with H5 haemagglutinin but not N1 neuraminidase to address this question. In this study, we investigate whether cross-neutralizing antibodies in persons unexposed to H5N1 is reactive to the H5 haemagglutinin. METHODOLOGY/PRINCIPAL FINDINGS: We measured H5-neutralization antibody titers pre- and post-vaccination using the H5N1 micro-neutralization test (MN and H5pp tests in subjects given seasonal vaccines and in selected sera from European elderly volunteers in a H5N1 vaccine trial who had detectable pre-vaccination H5N1 MN antibody titers. We found detectable (titer > or = 20 H5N1 neutralizing antibodies in a minority of pre-seasonal vaccine sera and evidence of a serological response to H5N1 in others after seasonal influenza vaccination. There was excellent correlation in the antibody titers between the H5N1 MN and H5pp tests. Similar correlations were found between MN and H5pp in the pre-vaccine sera from the cohort of H5N1 vaccine trial recipients. CONCLUSIONS/SIGNIFICANCE: Heterosubtype neutralizing antibody to H5N1 in healthy volunteers unexposed to H5N1 is mediated by cross-reaction to the H5 haemagglutinin.

  12. Concentrations of Pneumococcal IgA and IgM are compromised in some individuals with antibody deficiencies.

    Science.gov (United States)

    Echeverría de Carlos, Ainara; Gómez de la Torre, Ricardo; García Carus, Enrique; Caminal Montero, Luis; Bernardino Díaz López, Jose; Suárez Casado, Hector; Molinos Matin, Luis; Tricas Aizpún, Lourdes; Harding, Stephen; Parker, Antony R

    2017-06-15

    The response to pneumococcal vaccination is assessed by measurement of antigen specific IgG only and is compromised in a number of antibody deficiencies. We measured the concentrations of Pneumococcal IgA and IgM in individuals with both normal and abnormal pneumococcal capsular polysaccharide (PCP) IgG concentrations. A higher number of individuals had abnormal pre-vaccination IgA and IgM concentrations below the lower limit of the normal range compared to the control group. Post vaccination a lower number of individuals had IgA and IgM concentrations below the upper limit of the normal range compared to the control group. Non responders had a higher percentage of individuals with a prior history of infection. In addition, individuals with a history of prior infection had lower pre- and post-vaccination concentrations of PCP IgG, IgA, and IgM. Post-vaccination IgA and IgM concentrations identified four groups of responses which correlated with prior history of infection. A higher percentage of individuals with abnormal PCP IgA and IgM concentrations had a history of prior infection compared to the percentage of individuals with normal concentrations. In individuals with an antibody deficiency, measurement of Pneumococcal IgA and IgM correlates with the number of individuals with prior history of infection.

  13. COMPARATIVE DETECTION OF MEASLES SPECIFIC IGM ANTIBODY IN SERUM AND SALIVA BY AN ANTIBODY-CAPTURE IGM ENZYME IMMUNOASSAY (EIA)

    OpenAIRE

    Talat Mokhtari Azad; Anahid Ehteda; Parvin Yavari; R Hamkar; Zahra Safar Pour; M. Essalat Rakhsheh Nategh

    2003-01-01

    Laboratory diagnosis of acute measles is usually achieved by serology assays for measle-specific IgM antibody. For comparison of measle-specific IgM antibody in saliva and serum, 95 paired blood and saliva samples were collected 1-14 days after the onset of rash. The specimens were tested for specific IgM antibody by an IgM antibody-capture Enzyme Immunoassay (EIA). Measles IgM antibody was detected in 89 (93.7%) of serum samples and in 85(89.5%) of saliva specimens. Of the 6(6.3%) serum samp...

  14. Modulation of immune response by bacterial lipopolysaccharide (LPS): cellular basis of stimulatory and inhibitory effects of LPS on the in vitro IGM antibody response to a T-dependent antigen

    Energy Technology Data Exchange (ETDEWEB)

    Uchiyama, T.; Jacobs, D.M.

    1978-12-01

    The role of thymus-derived lymphocytes (T cells) in LPS modulation of T cell-development antibody responses has been investigated. We have assessed the effect of LPS on the primary anti-TNP response to TNP-SRBC of cultures of whole spleen cells or T cell-depleted spleen cells that were supplemented with various subpopulations of carrier-primed (SRBC) spleen cells. The TNP-PFC response was enhanced in the presence of irradiated SRBC-primed spleen cells by addition of 0.16 to 20 ..mu..g/ml LPS, but inhibition was observed when irradiation of primed cells was omitted. Enhancement but no inhibition occurred when added primed cells were first passed through a nylon wool column. LPS-mediated enhancement was dependent on a T cell in the primed population. These results suggest that LPS modulation of antibody synthesis is dependent on two populations of antigen-specific cells that have opposing effects on B cell responses to a T-dependent antigen: a helper cell that is irradiation resistant, nonadherent to nylon wool, and sensitive to anti-T cell serum, and a suppressor cell that is irradiation sensitive and adherent to nylon wool.

  15. Tetravalent dengue DIIIC protein together with alum and ODN elicits a Th1 response and neutralizing antibodies in mice.

    Science.gov (United States)

    Zuest, Roland; Valdes, Iris; Skibinski, David; Lin, Yufang; Toh, Ying Xiu; Chan, Katherine; Hermida, Lisset; Connolly, John; Guillen, Gerardo; Fink, Katja

    2015-03-17

    Dengue disease is a global challenge for healthcare systems particularly during outbreaks, and millions of dollars are spent every year for vector control. An efficient and safe vaccine that is cost-effective could resolve the burden that dengue virus imposes on affected countries. We describe here the immunogenicity of a tetravalent formulation of a recombinant fusion protein consisting of E domain III and the capsid protein of dengue serotypes 1-4 (Tetra DIIIC). E domain III is an epitope for efficient neutralizing antibodies while the capsid protein contains T cell epitopes. Besides combining B and T cell epitopes, Tetra DIIIC is highly immunogenic due to its aggregate form and a two-component adjuvant. Following previous studies assessing the monovalent DIIIC formulations, we addressed here the quality and breadth of the T cell- and antibody response of Tetra DIIIC in mice. Tetra DIIIC induced a Th1-type response against all four DENV serotypes and dengue-specific antibodies were predominantly IgG1 and IgG2a and neutralizing, while the induction of neutralizing antibodies was dependent on IFN signaling. Importantly, the Th1 and IgG1/IgG2a profile of the DIIIC vaccine approach is similar to an efficient natural anti-dengue response.

  16. Natural IgM switches the function of LPS activated murine bone marrow dendritic cells (BMDC) to a “regulatory” DC that suppresses innate inflammation1

    OpenAIRE

    Lobo, Peter I.; Schlegel, Kailo H.; Bajwa, Amandeep; Huang, Liping; Kurmaeva, Elvira; Wang, Binru; Ye, Hong; Tedder, Thomas F.; Kinsey, Gilbert R.; Okusa, Mark D.

    2015-01-01

    We have previously shown that polyclonal natural IgM protects mice from renal IRI by inhibiting the reperfusion inflammatory response. We hypothesized that a potential mechanism involved IgM modulation of dendritic cells as we observed high IgM binding to splenic DC. To test this hypothesis, we pre-treated BMDC with polyclonal murine or human IgM prior to LPS activation and demonstrate that 0.5 × 106 IgM/LPS pretreated BMDC, when injected into WT-B6 mice, 24 hours before renal ischemia, prote...

  17. Antibody class capture assay (ACCA) for rubella-specific IgM antibody.

    Science.gov (United States)

    Isaac, M; Payne, R A

    1982-01-01

    Enzyme-linked immunosorbent assays for IgM antirubella were carried out on 1,546 sera, using an IgM capture method with a F (ab')2 conjugate (ACCA). Under the conditions described, sera containing IgM antirubella bound up to 15 times as much enzyme activity as negative specimens. Paired serum specimens from 27 patients, serial serum specimens from 6 patients, and single serum specimens from 15 patients who had had recent rubella were examined by the haemagglutination inhibition test (HAI) in the presence and absence of 2-mercaptoethanol following sucrose density gradient centrifugation (SDGC). ACCA confirmed all the results found with HAI following SDGC. Specimens were examined from ten patients with congenital rubella; ACCA confirmed the results found with both immunofluorescence following SDGC and radioimmunoassay. Pre- and post-vaccination specimens from 123 patients who had been vaccinated against rubella were examined. An IgM response could only be demonstrated in the 57 cases when IgG was absent in the first specimen. The specificity of the assay was confirmed by testing 31 serum specimens from rubella immune patients that also contained rheumatoid factor, 163 serum specimens from patients with acute infections other than rubella, and 12 serum specimens from infants with miscellaneous neonatal abnormalities other than congenital rubella. The ACCA proved a simple, sensitive, and specific test for IgM antirubella and the results compared favourably with those obtained by the SDGC technique.

  18. Heart Rate Responses to Unaided Orion Side Hatch Egress in the Neutral Buoyancy Laboratory

    Science.gov (United States)

    English, Kirk L.; Hwang Emma Y.; Ryder, Jeffrey W.; Kelly, Cody; Walker, Thomas; Ploutz-Snyder, Lori L.

    2016-01-01

    NASA is developing the Orion capsule as a vehicle for transporting crewmembers to and from the International Space Station (ISS) and for future human space exploration missions. Orion and other commercial vehicles are designed to splash down in the ocean where nominally support personnel will assist crewmembers in egressing the vehicle. However, off-nominal scenarios will require crewmembers to egress the vehicle unaided, deploy survival equipment, and ingress a life raft. PURPOSE: To determine the heart rate (HR) responses to unaided Orion side hatch egress and raft ingress as a part of the NASA Crew Survival Engineering Team's evaluation of the PORT Orion mockup in the Neutral Buoyancy Laboratory (NBL). METHODS: Nineteen test subjects, including four astronauts (N=19, 14 males/5 females, 38.6+/-8.4 y, 174.4+/-9.6 cm, 75.7+/-13.1 kg), completed a graded maximal test on a cycle ergometer to determine VO2peak and HRpeak and were divided into five crews of four members each; one subject served on two crews. Each crew was required to deploy a life raft, egress the Orion vehicle from the side hatch, and ingress the life raft with two 8 kg emergency packs per crew. Each crew performed this activity one to three times; a total of ten full egresses were completed. Subjects wore a suit that was similar in form, mass, and function to the Modified Advanced Crew Escape Suit (MACES) including helmet, gloves, boots, supplemental O2 bottles, and a CO2-inflated life preserver (approx.18 kg); subjects began each trial seated supine in the PORT Orion mockup with seat belts and mockup O2 and communication connections and ended each trial with all four crewmembers inside the life raft. RESULTS: VO2peak was 40.8+/-6.8 mL/kg/min (3.1+/-0.7 L/min); HRpeak was 181+/-10 bpm. Total egress time across trials was 5.0+/-1.6 min (range: 2.8-8.0 min); all subjects were able to successfully complete all trials. Average maximum HR at activity start, at the hatch opening, in the water, and in the

  19. IgM repertoire biodiversity is reduced in HIV-1 infection and systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Li eYin

    2013-11-01

    Full Text Available Background: HIV-1 infection or systemic lupus erythematosus [SLE] disrupt B cell homeostasis, reduce memory B cells, and impair function of IgG and IgM antibodies. Objective: To determine how disturbances in B cell populations producing polyclonal antibodies relate to the IgM repertoire, the IgM transcriptome in health and disease was explored at the complementarity determining region 3 [CDRH3] sequence population level. Methods: 454-deep pyrosequencing in combination with a novel analysis pipeline was applied to define populations of IGHM CDRH3 sequences based on absence or presence of somatic hypermutations [SHM] in peripheral blood B cells. Results: HIV or SLE subjects have reduced biodiversity within their IGHM transcriptome compared to healthy subjects, mainly due to a significant decrease in the number of unique combinations of alleles, although recombination machinery was intact. While major differences between sequences without or with SHM occurred among all groups, IGHD and IGHJ allele use, CDRH3 length distribution, or generation of SHM were similar among study cohorts. Antiretroviral therapy failed to normalize IGHM biodiversity in HIV-infected individuals. All subjects had a low frequency of allelic combinations within the IGHM repertoire similar to known broadly-neutralizing HIV-1 antibodies. Conclusions: Polyclonal expansion would decrease overall IgM biodiversity independent of other mechanisms for development of the B cell repertoire. Applying deep sequencing as a strategy to follow development of the IgM repertoire in health and disease provides a novel molecular assessment of multiple points along the B cell differentiation pathway that is highly sensitive for detecting perturbations within the repertoire at the population level.

  20. Pediatric Selective IgM Immunodeficiency

    Directory of Open Access Journals (Sweden)

    Marc F. Goldstein

    2008-01-01

    Full Text Available Objective. Limited information exists on features of pediatric Selective IgM immunodeficiency (SIgMID. Previously published pediatric cases and 2 new cases are reviewed. Methods. English literature from PubMed and references from relevant articles were reviewed. Previously reported cases and 2 new cases from an allergy/immunology practice were analyzed. Results. Forty-nine reported cases of SIgMID presented with respiratory infections (77.6%, gastrointestinal disease (16.3%, skin disease (12.2%, and meningitis (8.2%. Mean serum IgM level was 16.5±13.8 mg/dL. Two patients were identified with SIgMID among 6300 active pediatric patients (0.03% presenting with asthma, vasomotor rhinitis, and recurrent respiratory infections. In the 51 cases reported, none developed lymphoproliferative disease nor evolved into panhypogammaglobulinemia; four fatalities were reported. Conclusions. The prevalence of SIgMID in our pediatric population was 0.03%. In general, respiratory infections are the common comorbid conditions. Death and autoimmune disease are uncommon complications of pediatric SIgMID.

  1. Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs

    Science.gov (United States)

    Persson, Josefine; Zhang, Yuan; Olafsdottir, Thorunn A.; Thörn, Karolina; Cairns, Tina M.; Wegmann, Frank; Sattentau, Quentin J.; Eisenberg, Roselyn J.; Cohen, Gary H.; Harandi, Ali M.

    2016-01-01

    Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes. PMID:28082979

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

    DEFF Research Database (Denmark)

    Frederiksen, J L; Sorensen, P S; Hesse, D;

    2009-01-01

    BACKGROUND AND PURPOSE: Neutralizing antibodies (NAbs) appearing during treatment with Interferon-beta (IFN-beta) reduce or abolish bioactivity and therapeutic efficacy. Initial combination therapy with methylprednisolone (MP) may reduce the frequency of NAb positive patients. We hypothesized...... that MP treatment might also reduce NAb levels and re-establish IFN-beta bioactivity in patients already NAb+, who discontinue IFN-beta therapy. METHODS: In a 6-month open-label trial, we compared monthly high-dose pulsed MP treatment in 38 Nab positive patients with 35 NAb+, MP-untreated control patients...... discontinuing any therapy or switching to glatiramer acetate. All patients were NAb+ with an absent in vivo response to IFN-beta. NAbs were measured using a cytopathic effect assay and expressed as neutralizing capacity (NC) in percentage of added IFN-beta. Bioactivity was expressed as in vivo Myxovirus...

  3. Chimeric rhinoviruses displaying MPER epitopes elicit anti-HIV neutralizing responses.

    Directory of Open Access Journals (Sweden)

    Guohua Yi

    Full Text Available BACKGROUND: The development of an effective AIDS vaccine has been a formidable task, but remains a critical necessity. The well conserved membrane-proximal external region (MPER of the HIV-1 gp41 glycoprotein is one of the crucial targets for AIDS vaccine development, as it has the necessary attribute of being able to elicit antibodies capable of neutralizing diverse isolates of HIV. METHODOLOGY/PRINCIPLE FINDINGS: Guided by X-ray crystallography, molecular modeling, combinatorial chemistry, and powerful selection techniques, we designed and produced six combinatorial libraries of chimeric human rhinoviruses (HRV displaying the MPER epitopes corresponding to mAbs 2F5, 4E10, and/or Z13e1, connected to an immunogenic surface loop of HRV via linkers of varying lengths and sequences. Not all libraries led to viable chimeric viruses with the desired sequences, but the combinatorial approach allowed us to examine large numbers of MPER-displaying chimeras. Among the chimeras were five that elicited antibodies capable of significantly neutralizing HIV-1 pseudoviruses from at least three subtypes, in one case leading to neutralization of 10 pseudoviruses from all six subtypes tested. CONCLUSIONS: Optimization of these chimeras or closely related chimeras could conceivably lead to useful components of an effective AIDS vaccine. While the MPER of HIV may not be immunodominant in natural infection by HIV-1, its presence in a vaccine cocktail could provide critical breadth of protection.

  4. IgM, FcµRs, and malarial immune evasion

    DEFF Research Database (Denmark)

    Czajkowsky, Daniel M; Salanti, Ali; Ditlev, Sisse B;

    2010-01-01

    , particularly in light of the just-discovered FcmicroR localized to B and T cell surfaces. Because this parasite may exploit an interaction with IgM to limit immune detection, as well as to manipulate the immune response when detected, a better understanding of this association may prove critical...

  5. The etiology of Rubella IgM positivity in patients with rubella-like illness in Iran from 2011 to 2013.

    Science.gov (United States)

    Khorrami, Seyed Mahmood Seyed; Mokhtari-Azad, Talat; Yavarian, Jila; Nasab, Gazal Sadat Fatemi; Naseri, Maryam; Jandaghi, Nazanin Zahra Shafiei

    2015-11-01

    Rubella is a mild self-limiting contagious viral disease caused by the rubella virus (RV). Although symptoms are often mild, the concern is centralized around the possible effect on a fetus growth and development in case of primary infection during early months of pregnancy. Recently acquired rubella is commonly confirmed by RV-specific IgM antibody detection in the serum. However, rubella primary infection is not always the only cause of IgM positivity. Other possible causes of rubella IgM positivity may include IgM persistence following vaccination or naturally acquired infection or even re-infection. Moreover, nonspecific IgM reactivity can cause false-positive results. There are few articles to differentiate the aetiology of rash in rubella-like illnesses. However, limited studies have been conducted on clarifying the source of IgM positivity in these cases. This article reports the study of 10,896 clinical cases demonstrating rubella-like illness between 2011 and 2013 in Iran. The rate of IgM positivity among these cases was 0.52% (57 cases). As predicted based on the high coverage of vaccination in Iran fewer than 16% of cases with ELISA IgM positive result, were due to current rubella primary infections. The greater part of the positive IgM reactions occurred in cross reactivity with other viruses (31.6%) or in prolonged IgM response post vaccination (24.6%). This research confirmed that the positive result of rubella IgM assay in vaccinated individuals is mainly caused by prolonged IgM production, rubella re-infection, and false positivity due to infection with other viruses, rather than the rubella primary infection itself.

  6. Purification of Murine Monoclonal IgM Antibody

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    This paper presents the purification of a monoclonal IgM antibody against human tumor associated antigen Lewis-Y by ion exchange chromatography and gel filtration.Enzyme-linked immunosorbent assay (ELISA) and SDS-polyacrylamide gel electrophoresis (PAGE) were used to identify purified IgM antibody.In flow cytometry analysis, the purified IgM antibody recognizes human breast tumor cell line MCF-7 which expresses Lewis-Y antigen.This work presents a new way for the purification of murine monoclonal IgM antibody.

  7. IgM in the kidney: a multiple personality disorder.

    Science.gov (United States)

    Platt, Jeffrey L; Cascalho, Marilia

    2015-09-01

    IgM in the blood of normal individuals consists mainly of 'natural' polyreactive antibodies. Natural IgM is thought to provide an initial defense against infection and to promote the healing of wounded cells. Yet, as Panzer and colleagues show, these benefits can be eclipsed when the IgM binds to damaged cells of the glomerulus, activating complement. IgM in glomeruli thus signifies cellular damage and may warn that the pace of that damage exceeds the capacity for repair.

  8. Children with invasive Staphylococcus aureus disease exhibit a potently neutralizing antibody response to the cytotoxin LukAB.

    Science.gov (United States)

    Thomsen, Isaac P; Dumont, Ashley L; James, David B A; Yoong, Pauline; Saville, Benjamin R; Soper, Nicole; Torres, Victor J; Creech, C Buddy

    2014-03-01

    Despite the importance of Staphylococcus aureus as a common invasive bacterial pathogen, the humoral response to infection remains inadequately defined, particularly in children. The purpose of this study was to assess the humoral response to extracellular staphylococcal virulence factors, including the bicomponent leukotoxins, which are critical for the cytotoxicity of S. aureus toward human neutrophils. Children with culture-proven S. aureus infection were prospectively enrolled and stratified by disease type. Fifty-three children were enrolled in the study, of which 90% had invasive disease. Serum samples were obtained during the acute (within 48 h) and convalescent (4 to 6 weeks postinfection) phases, at which point both IgG titers against S. aureus exotoxins were determined, and the functionality of the generated antibodies was evaluated. Molecular characterization of clinical isolates was also performed. We observed a marked rise in antibody titer from acute-phase to convalescent-phase sera for LukAB, the most recently described S. aureus bicomponent leukotoxin. LukAB production by the isolates was strongly correlated with cytotoxicity in vitro, and sera containing anti-LukAB antibodies potently neutralized cytotoxicity. Antibodies to S. aureus antigens were detectable in healthy pediatric controls but at much lower titers than in sera from infected subjects. The discovery of a high-titer, neutralizing antibody response to LukAB during invasive infections suggests that this toxin is produced in vivo and that it elicits a functional humoral response.

  9. Starburst Galaxies: Outflows of Metals and Energy into the IGM

    CERN Document Server

    Strickland, David K; Ptak, Andrew; Schlegel, Eric; Tremonti, Christy; Tsuru, Takeshi; Tuellmann, Ralph; Zezas, Andreas

    2009-01-01

    What is the contribution of mass, metals and energy from starburst galaxies to the Intergalactic Medium? Starburst galaxies drive galactic-scale outflows or "superwinds" that may be responsible for removing metals from galaxies and polluting the Intergalactic Medium (IGM). In the last decade tremendous progress was made in mapping cool entrained gas in superwinds through UV/optical imaging and absorption line spectroscopy. These studies demonstrated that superwinds are ubiquitous in galaxies forming stars at high surface densities and that the most powerful starbursts can drive outflows near escape velocity. Theoretical models of galaxy evolution have begun to incorporate superwinds, using various ad-hoc prescriptions based on our knowledge of the cool gas. However, these efforts are fundamentally impeded by our lack of information about the hot phase of these outflows. The hot X-ray emitting phase of a superwind contains the majority of its energy and newly-synthesized metals, and given its high specific ene...

  10. Chemokine receptor polymorphism and autologous neutralizing antibody response in long-term HIV-1 infection

    DEFF Research Database (Denmark)

    Schønning, Kristian; Joost, Mette; Gram, G J;

    1998-01-01

    samples. Finally, late virus isolates from individuals with SPI generally remained sensitive to neutralization by early serum samples. Virus phenotype (SI/NSI) and CCR5 genotype was determined for all individuals. Neither showed significant correlation with SPI. However, all SPI individuals who were...... heterozygous for the CCR5 deletion were infected with virus of NSI phenotype. In contrast, all RPI individuals who were heterozygous for the CCR5 deletion were infected with virus of SI phenotype (p = .028). Thus, a beneficial effect of having a partly nonfunctional CCR5 coreceptor may depend on the viral SI...

  11. Four- and six-month-old infants' visual responses to joy, anger, and neutral expressions.

    Science.gov (United States)

    LaBarbera, J D; Izard, C E; Vietze, P; Parisi, S A

    1976-06-01

    24 infants, 12 4-month-olds and 12 6-month-olds, were repeatedly shown slides of 3 facial expressions. The expressions were previously judged by obervers to be indicators of joy, anger, and no emotion, respectively. The duration of the first visual fixation to each presentation of the slides was monitored for each subject. The data indicated that the infants looked at the joy expression significantly more than at either the anger or neutral expressions. The results suggest that infants are capable of discriminating emotion expressions earlier in their development than previous studies have implied.

  12. Induction of neutralizing antibody response against four dengue viruses in mice by intramuscular electroporation of tetravalent DNA vaccines.

    Science.gov (United States)

    Prompetchara, Eakachai; Ketloy, Chutitorn; Keelapang, Poonsook; Sittisombut, Nopporn; Ruxrungtham, Kiat

    2014-01-01

    DNA vaccine against dengue is an interesting strategy for a prime/boost approach. This study evaluated neutralizing antibody (NAb) induction of a dengue tetravalent DNA (TDNA) vaccine candidate administered by intramuscular-electroporation (IM-EP) and the benefit of homologous TDNA boosting in mice. Consensus humanized pre-membrane (prM) and envelope (E) of each serotypes, based on isolates from year 1962-2003, were separately cloned into a pCMVkan expression vector. ICR mice, five-six per group were immunized for three times (2-week interval) with TDNA at 100 µg (group I; 25 µg/monovalent) or 10 µg (group II; 2.5 µg/monovalent). In group I, mice received an additional TDNA boosting 13 weeks later. Plaque reduction neutralization tests (PRNT) were performed at 4 weeks post-last immunization. Both 100 µg and 10 µg doses of TDNA induced high NAb levels against all DENV serotypes. The median PRNT50 titers were comparable among four serotypes of DENV after TDNA immunization. Median PRNT50 titers ranged 240-320 in 100 µg and 160-240 in 10 µg groups (p = ns). A time course study of the 100 µg dose of TDNA showed detectable NAb at 2 weeks after the second injection. The NAb peaked at 4 weeks after the third injection then declined over time but remained detectable up to 13 weeks. An additional homologous TDNA boosting significantly enhanced the level of NAb from the nadir for at least ten-fold (pdengue viral strain for both vaccine immunogen design and neutralization assays is critical to avoid a mismatching outcome. In summary, this TDNA vaccine candidate induced good neutralizing antibody responses in mice; and the DNA/DNA prime/boost strategy is promising and warranted further evaluation in non-human primates.

  13. Potentiometric response of a neutral-carrier-based membrane to aqueous mercury in Cl(-)-rich media.

    Science.gov (United States)

    Kim, Yunmi; Kim, Jongwon; Kim, Kyoung Nam; Chang, Suk-Kyu; Chung, Taek Dong

    2009-04-01

    The unique potentiometric response of mercury sensors was investigated in aqueous Cl(-)-rich media, which are often encountered in natural, especially biological samples. The conventional neutral-carrier-based Hg(II)-ISEs are not practically useful because the Cl(-) concentrations in natural aqueous samples are normally too high for mercury to be present in the form of Hg(2+). Negative potentiometric slopes, which are the opposite behavior of the previously reported Hg(II)-ISEs, were experimentally confirmed and quantitatively reasoned based on the aqueous solution equilibrium of Hg(2+).

  14. Serum Treponema IgM Antibody Test for Syphilis Diagnosis

    Institute of Scientific and Technical Information of China (English)

    郑占才; 张荣富; 溪茜

    2003-01-01

    Objective: To evaluate the clinical utility of testing serum anti-treponema pallidum IgM antibody in the diagnosis of syphilis patients. Methods: Seventy-two cases of syphilis were tested for specific IgM antibody with ELISA, and the results were compared with RPR and TPPA.Results: The sensitivity of IgM antibody was 73.3 %(11/15) in primary syphilis, 88.9% (16/18) in sec-ondary syphilis, and there was no significant differ-ence between these values (x2=1.6363, P>0.10). The sensitivity of IgM antibody in diagnosing latent syphi-lis was only 26.1% (6/23), much lower than the detec-tion rate in symptomatic earlv svDhilis (x2=17.6189. P<0.005). RPR and TPPA were both 100% sensitive in latent and early symptomatic syphilis. Two were posi,five for IgM in the 16 cases who had received regular treatments 2 to 24 months before enrolled.Conclusions: Specific IgM antibody detection doees not appear superior to RPR and TPPA in diagnosing primary syphilis. The diagnosis of latent syphilis should mainly rely on RPR and TPPA, since there are low titers of IgM antibody at that stage. IgM antibody testing alone should not be recommended for monitor-ing syphilis development or treatment efficacy. Fur-ther studies should be concerned.

  15. Reporter gene assay for the quantification of the activity and neutralizing antibody response to TNFα antagonists

    DEFF Research Database (Denmark)

    Lallemand, Christophe; Kavrochorianou, Nadia; Steenholdt, Casper;

    2011-01-01

    relative to Renilla luciferase expression. Thus, results are independent of cell number or differences in cell viability, resulting in intra and inter assay coefficients of variation of 10% or less. Normalization of results relative to the expression of an internal standard also provides a means......A cell-based assay has been developed for the quantification of the activity of TNFa antagonists based on human erythroleukemic K562 cells transfected with a NF¿B regulated firefly luciferase reporter-gene construct. Both drug activity and anti-drug neutralizing antibodies can be quantified...... with a high degree of precision within 2h, and without interference from cytokines and other factors known to activate NF¿B. The assay cells also contain the Renilla luciferase reporter gene under the control of a constitutive promoter that allows TNFa-induced firefly luciferase activity to be normalized...

  16. Reporter gene assay for the quantification of the activity and neutralizing antibody response to TNFα antagonists

    DEFF Research Database (Denmark)

    Lallemand, Christophe; Kavrochorianou, Nadia; Steenholdt, Casper;

    2011-01-01

    relative to Renilla luciferase expression. Thus, results are independent of cell number or differences in cell viability, resulting in intra and inter assay coefficients of variation of 10% or less. Normalization of results relative to the expression of an internal standard also provides a means......A cell-based assay has been developed for the quantification of the activity of TNFα antagonists based on human erythroleukemic K562 cells transfected with a NFκB regulated firefly luciferase reporter-gene construct. Both drug activity and anti-drug neutralizing antibodies can be quantified...... with a high degree of precision within 2h, and without interference from cytokines and other factors known to activate NFκB. The assay cells also contain the Renilla luciferase reporter gene under the control of a constitutive promoter that allows TNFα-induced firefly luciferase activity to be normalized...

  17. Limited Neutrality

    DEFF Research Database (Denmark)

    Nielsen, Morten Ebbe Juul

    2006-01-01

    Article Concerning the prospect of a kind of limited neutrality in place of the standard liberal egalitarian "neutrality of justification."......Article Concerning the prospect of a kind of limited neutrality in place of the standard liberal egalitarian "neutrality of justification."...

  18. Limited Neutrality

    DEFF Research Database (Denmark)

    Nielsen, Morten Ebbe Juul

    2006-01-01

    Article Concerning the prospect of a kind of limited neutrality in place of the standard liberal egalitarian "neutrality of justification."......Article Concerning the prospect of a kind of limited neutrality in place of the standard liberal egalitarian "neutrality of justification."...

  19. Antibodies recognizing both IgM isotypes in Atlantic salmon

    DEFF Research Database (Denmark)

    Hedfors, Ida Aagård; Bakke, Hege; Skjødt, Karsten

    2012-01-01

    these molecules. The present study aimed at identifying tools to separate IgM positive (IgM(+)) B cells from IgM negative (IgM(-)) non-B cell populations using flow cytometry. Several monoclonal antibodies (mAbs), and one polyclonal antibody (pAb) to both rainbow trout (Oncorhynchus mykiss) and Atlantic salmon...... defined, mostly due to the lack of appropriate working tools like antibodies and functional assays. Membrane bound molecules like immunoglobulins (Ig) serve as cell surface markers for specific cell subsets and the identification of cells relies upon the production of specific antibodies towards...... of IgM(+) cells in the respective tissues in salmon. To our surprise, this seemingly simple task did not reveal similar staining patterns for all antibodies as expected, but rather large differences in the number of positively stained cells were discovered. In short, positively stained cells by each...

  20. Plasmodium falciparum synthetic LbL microparticle vaccine elicits protective neutralizing antibody and parasite-specific cellular immune responses.

    Science.gov (United States)

    Powell, Thomas J; Tang, Jie; Derome, Mary E; Mitchell, Robert A; Jacobs, Andrea; Deng, Yanhong; Palath, Naveen; Cardenas, Edwin; Boyd, James G; Nardin, Elizabeth

    2013-04-01

    Epitopes of the circumsporozoite (CS) protein of Plasmodium falciparum, the most pathogenic species of the malaria parasite, have been shown to elicit protective immunity in experimental animals and human volunteers. The mechanisms of immunity include parasite-neutralizing antibodies that can inhibit parasite motility in the skin at the site of infection and in the bloodstream during transit to the hepatocyte host cell and also block interaction with host cell receptors on hepatocytes. In addition, specific CD4+ and CD8+ cellular mechanisms target the intracellular hepatic forms, thus preventing release of erythrocytic stage parasites from the infected hepatocyte and the ensuing blood stage cycle responsible for clinical disease. An innovative method for producing particle vaccines, layer-by-layer (LbL) fabrication of polypeptide films on solid CaCO3 cores, was used to produce synthetic malaria vaccines containing a tri-epitope CS peptide T1BT comprising the antibody epitope of the CS repeat region (B) and two T-cell epitopes, the highly conserved T1 epitope and the universal epitope T. Mice immunized with microparticles loaded with T1BT peptide developed parasite-neutralizing antibodies and malaria-specific T-cell responses including cytotoxic effector T-cells. Protection from liver stage infection following challenge with live sporozoites from infected mosquitoes correlated with neutralizing antibody levels. Although some immunized mice with low or undetectable neutralizing antibodies were also protected, depletion of T-cells prior to challenge resulted in the majority of mice remaining resistant to challenge. In addition, mice immunized with microparticles bearing only T-cell epitopes were not protected, demonstrating that cellular immunity alone was not sufficient for protective immunity. Although the microparticles without adjuvant were immunogenic and protective, a simple modification with the lipopeptide TLR2 agonist Pam3Cys increased the potency and

  1. Watching neutral and threatening movies: subjective experience and autonomic responses in subjects with different hypnotizability levels.

    Science.gov (United States)

    Santarcangelo, E L; Paoletti, G; Balocchi, R; Scattina, E; Ghelarducci, B; Varanini, M

    2012-04-01

    Subjects with high hypnotizability scores (Highs) have been considered more prone to experience negative affect and more vulnerable to its autonomic effects with respect to low hypnotizable individuals (Lows). The aim of the study was to analyze the subjective experience, tonic skin conductance (SC), respiratory frequency (RF), heart rate (HR) and heart rate variability (HRV) of healthy Highs and Lows during a long-lasting, emotionally neutral task (Session R, 46 subjects) and a moderately threatening one (Session T, 35 subjects). At the end of the relaxing Session R, all participants reported an increased relaxation. At the end of the threatening Session T, only 20 subjects reported a decreased relaxation (effective T: eT subsample). Highs and Lows of this subsample reported a similarly reduced relaxation and showed a similarly increased skin conductance. HR and HRV did not differ between the two sessions and between Highs and Lows. Among the subjects not reporting decreased relaxation at the end of Session T (ineffective T: iT subsample, n=15), relaxation was deeper and associated with lower skin conductance in Highs, although HR and HRV did not differ between Highs and Lows. All together, the results do not support the hypothesis of higher proneness of Highs to experience negative affect and to exhibit the autonomic correlates of negative emotion.

  2. Virus-neutralizing antibody response of mice to consecutive infection with human and avian influenza A viruses.

    Science.gov (United States)

    Janulíková, J; Stropkovská, A; Bobišová, Z; Košík, I; Mucha, V; Kostolanský, F; Varečková, E

    2015-06-01

    In this work we simulated in a mouse model a naturally occurring situation of humans, who overcame an infection with epidemic strains of influenza A, and were subsequently exposed to avian influenza A viruses (IAV). The antibody response to avian IAV in mice previously infected with human IAV was analyzed. We used two avian IAV (A/Duck/Czechoslovakia/1956 (H4N6) and the attenuated virus rA/Viet Nam/1203-2004 (H5N1)) as well as two human IAV isolates (virus A/Mississippi/1/1985 (H3N2) of medium virulence and A/Puerto Rico/8/1934 (H1N1) of high virulence). Two repeated doses of IAV of H4 or of H5 virus elicited virus-specific neutralizing antibodies in mice. Exposure of animals previously infected with human IAV (of H3 or H1 subtype) to IAV of H4 subtype led to the production of antibodies neutralizing H4 virus in a level comparable with the level of antibodies against the human IAV used for primary infection. In contrast, no measurable levels of virus-neutralizing (VN) antibodies specific to H5 virus were detected in mice infected with H5 virus following a previous infection with human IAV. In both cases the secondary infection with avian IAV led to a significant increase of the titer of VN antibodies specific to the corresponding human virus used for primary infection. Moreover, cross-reactive HA2-specific antibodies were also induced by sequential infection. By virtue of these results we suggest that the differences in the ability of avian IAV to induce specific antibodies inhibiting virus replication after previous infection of mice with human viruses can have an impact on the interspecies transmission and spread of avian IAV in the human population.

  3. IGMS: An Integrated ISO-to-Appliance Scale Grid Modeling System

    Energy Technology Data Exchange (ETDEWEB)

    Palmintier, Bryan; Hale, Elaine; Hansen, Timothy M.; Jones, Wesley; Biagioni, David; Sorensen, Harry; Wu, Hongyu; Hodge, Bri-Mathias

    2017-05-01

    This paper describes the Integrated Grid Modeling System (IGMS), a novel electric power system modeling platform for integrated transmission-distribution analysis that co-simulates off-the-shelf tools on high performance computing (HPC) platforms to offer unprecedented resolution from ISO markets down to appliances and other end uses. Specifically, the system simultaneously models hundreds or thousands of distribution systems in co-simulation with detailed Independent System Operator (ISO) markets and AGC-level reserve deployment. IGMS uses a new MPI-based hierarchical co-simulation framework to connect existing sub-domain models. Our initial efforts integrate opensource tools for wholesale markets (FESTIV), bulk AC power flow (MATPOWER), and full-featured distribution systems including physics-based end-use and distributed generation models (many instances of GridLAB-D[TM]). The modular IGMS framework enables tool substitution and additions for multi-domain analyses. This paper describes the IGMS tool, characterizes its performance, and demonstrates the impacts of the coupled simulations for analyzing high-penetration solar PV and price responsive load scenarios.

  4. Gaseous haloes : Linking galaxies to the IGM

    NARCIS (Netherlands)

    Fraternali, Filippo; Binney, James; Oosterloo, Tom; Sancisi, Renzo

    2007-01-01

    In recent years, evidence has accumulated that nearby spiral galaxies are surrounded by massive haloes of neutral and ionised gas. These gaseous haloes rotate more slowly than the disks and show inflow motions. They are clearly analogous to the High Velocity Clouds of the Milky Way. We show that the

  5. Role of Inositol Phosphosphingolipid Phospholipase C1, the Yeast Homolog of Neutral Sphingomyelinases in DNA Damage Response and Diseases

    Directory of Open Access Journals (Sweden)

    Kaushlendra Tripathi

    2015-01-01

    Full Text Available Sphingolipids play a very crucial role in many diseases and are well-known as signaling mediators in many pathways. Sphingolipids are produced during the de novo process in the ER (endoplasmic reticulum from the nonsphingolipid precursor and comprise both structural and bioactive lipids. Ceramide is the central core of the sphingolipid pathway, and its production has been observed following various treatments that can induce several different cellular effects including growth arrest, DNA damage, apoptosis, differentiation, and senescence. Ceramides are generally produced through the sphingomyelin hydrolysis and catalyzed by the enzyme sphingomyelinase (SMase in mammals. Presently, there are many known SMases and they are categorized into three groups acid SMases (aSMases, alkaline SMases (alk-SMASES, and neutral SMases (nSMases. The yeast homolog of mammalians neutral SMases is inositol phosphosphingolipid phospholipase C. Yeasts generally have inositol phosphosphingolipids instead of sphingomyelin, which may act as a homolog of mammalian sphingomyelin. In this review, we shall explain the structure and function of inositol phosphosphingolipid phospholipase C1, its localization inside the cells, mechanisms, and its roles in various cell responses during replication stresses and diseases. This review will also give a new basis for our understanding for the mechanisms and nature of the inositol phosphosphingolipid phospholipase C1/nSMase.

  6. Effect of delayed anthrax vaccine dose on Bacillus anthracis protective antigen IgG response and lethal toxin neutralization activity.

    Science.gov (United States)

    Pittman, Phillip R; Fisher, Diana; Quinn, Xiaofei; Schmader, Trevor; Barrera-Oro, Julio G

    2013-10-17

    We describe the Bacillus anthracis protective antigen IgG antibody response and the B. anthracis lethal toxin neutralization activity to a delayed dose of anthrax vaccine adsorbed (AVA, BioThrax(®)) using validated assays. 373 individuals received 1, 2, or 3 priming doses, 18-24 months afterward, they received a delayed dose of AVA. Overall, 23.6% of subjects showed detectable anti-PA IgG before the boost, compared to 99.2% (P<0.0001) 28 days after the boost. Geometric mean anti-PA IgG concentration (GMC) was 1.66 μg/mL before and 887.82 μg/mL after the boost (P<0.0001). The proportion of individuals with four-fold increase in GMC following the boost ranged from 93.8% to 100%. Robust anti-PA IgG levels and B. anthracis lethal toxin neutralization activity are induced when an AVA dose is delayed as long as two years. These data support continuing with the vaccination schedule when a dose is delayed as long as two years rather than restarting the series.

  7. Variable epitope libraries: new vaccine immunogens capable of inducing broad human immunodeficiency virus type 1-neutralizing antibody response.

    Science.gov (United States)

    Charles-Niño, Claudia; Pedroza-Roldan, Cesar; Viveros, Monica; Gevorkian, Goar; Manoutcharian, Karen

    2011-07-18

    The extreme antigenic variability of human immunodeficiency virus (HIV) leads to immune escape of the virus, representing a major challenge in the design of effective vaccine. We have developed a novel concept for immunogen construction based on introduction of massive mutations within the epitopes targeting antigenically variable pathogens and diseases. Previously, we showed that these immunogens carrying large combinatorial libraries of mutated epitope variants, termed as variable epitope libraries (VELs), induce potent, broad and long lasting CD8+IFN-γ+ T-cell response. Moreover, we demonstrated that these T cells recognize more than 50% of heavily mutated variants (5 out of 10 amino acid positions were mutated in each epitope variant) of HIV-1 gp120 V3 loop-derived cytotoxic T lymphocyte epitope (RGPGRAFVTI) in mice. The constructed VELs had complexities of 10000 and 12500 individual members, generated as plasmid DNA or as M13 phage display combinatorial libraries, respectively, and with structural composition RGPGXAXXXX or XGXGXAXVXI, where X is any of 20 natural amino acids. Here, we demonstrated that sera from mice immunized with these VELs are capable of neutralizing 5 out of 10 viral isolates from Tier 2 reference panel of subtype B envelope clones, including HIV-1 isolates which are known to be resistant to neutralization by several potent monoclonal antibodies, described previously. These data indicate the feasibility of the application of immunogens based on VEL concept as an alternative approach for the development of molecular vaccines against antigenically variable pathogens.

  8. Understanding the IGM Through the Use of a Lensed Quasar

    Science.gov (United States)

    Panurach, Teresa; O'Dowd, Matthew

    2017-01-01

    Quasars are among the brightest objects in the universe. In rare gravitationally lensed quasars, their light is split and travels along multiple paths through an intervening lensing galaxy. The light that follows these different paths encounters various parts of the intergalactic medium (IGM) and may show different absorption features, indicating the varying composition of the IGM. By analyzing spectra from a gravitationally lensed quasar, B1422+231, observed by the Gemini North Telescope, we compare the absorption features identified in the lensed images to form a small-scale structure of the IGM.

  9. Vaccination of rhesus macaques with the live-attenuated HSV-1 vaccine VC2 stimulates the proliferation of mucosal T cells and germinal center responses resulting in sustained production of highly neutralizing antibodies.

    Science.gov (United States)

    Stanfield, Brent A; Pahar, Bapi; Chouljenko, Vladimir N; Veazey, Ronald; Kousoulas, Konstantin G

    2017-01-23

    We have shown that the live-attenuated HSV-1 VC2 vaccine strain with mutations in glycoprotein K (gK) and the membrane protein UL20 is unable to establish latency in vaccinated animals and produces a robust immune response capable of completely protecting mice against lethal vaginal HSV-1 or HSV-2 infections. To better understand the immune response generated by vaccination with VC2, we tested its ability to elicit immune responses in rhesus macaques. Vaccinated animals showed no signs of disease and developed increasing HSV-1 and HSV-2 reactive IgG1 after two booster vaccinations, while IgG subtypes IgG2 and IgG3 remained at low to undetectable levels. All vaccinated animals produced high levels of cross protective neutralizing antibodies. Flow cytometry analysis of cells isolated from draining lymph nodes showed that VC2 vaccination stimulated significant increases in plasmablast (CD27(high)CD38(high)) and mature memory (CD21(-)IgM(-)) B cells. T cell analysis on cells isolated from draining lymph node biopsies demonstrated a statistically significant increase in proliferating (Ki67(+)) follicular T helper cells and regulatory CXCR5(+) CD8(+) cytotoxic T cells. Analysis of plasma isolated two weeks post vaccination showed significant increases in circulating CXCL13 indicating increased germinal center activity. Cells isolated from vaginal biopsy samples collected over the course of the study exhibited vaccination-dependent increases in proliferating (Ki67(+)) CD4(+) and CD8(+) T cell populations. These results suggest that intramuscular vaccination with the live-attenuated HSV-1 VC2 vaccine strain can stimulate robust IgG1 antibody responses that persist for >250days post vaccination. In addition, vaccination lead to the maturation of B cells into plasmablast and mature memory B cells, the expansion of follicular T helper cells, and affects in the mucosal immune responses. These data suggest that the HSV VC2 vaccine induces potent immune responses that could help

  10. Electromagnetic and neutral-weak response functions of 4He and 12C

    Science.gov (United States)

    Lovato, A.; Gandolfi, S.; Carlson, J.; Pieper, Steven C.; Schiavilla, R.

    2015-06-01

    Background: A major goal of nuclear theory is to understand the strong interaction in nuclei as it manifests itself in terms of two- and many-body forces among the nuclear constituents, the protons and neutrons, and the interactions of these constituents with external electroweak probes via one- and many-body currents. Purpose: The objective of the present work is to calculate the quasielastic electroweak response functions in light nuclei within the realistic dynamical framework outlined above. These response functions determine the inclusive cross section as function of the lepton momentum and energy transfers. Methods: Their ab initio calculation is a very challenging quantum many-body problem, since it requires summation over the entire excitation spectrum of the nucleus and inclusion in the electroweak currents of one- and many-body terms. Green's functions Monte Carlo methods allow one to circumvent both difficulties by computing the response in imaginary time (the so-called Euclidean response) and hence summing implicitly over the bound and continuum states of the nucleus, and by implementing specific algorithms designed to deal with the complicated spin-isospin structure of nuclear many-body operators. Results: Theoretical predictions for 4He and 12C, confirmed by experiment in the electromagnetic case, show that two-body currents generate excess transverse strength from threshold to the quasielastic to the dip region and beyond. Conclusions: These results challenge the conventional picture of quasielastic inclusive scattering as being largely dominated by single-nucleon knockout processes.

  11. The Limits of Corporate Social Responsibility: Techniques of Neutralization, Stakeholder Management and Political CSR

    OpenAIRE

    Fooks, G.; Gilmore, A; Collin, J; Holden, C.; Lee, K.

    2013-01-01

    : Since scholarly interest in corporate social responsibility (CSR) has primarily focused on the synergies between social and economic performance, our understanding of how (and the conditions under which) companies use CSR to produce policy outcomes that work against public welfare has remained comparatively under-developed. In particular, little is known about how corporate decision-makers privately reconcile the conflicts between public and private interests, even though this is likely to ...

  12. Complement deposition in autoimmune hemolytic anemia is a footprint for difficult-to-detect IgM autoantibodies.

    Science.gov (United States)

    Meulenbroek, Elisabeth M; de Haas, Masja; Brouwer, Conny; Folman, Claudia; Zeerleder, Sacha S; Wouters, Diana

    2015-11-01

    In autoimmune hemolytic anemia autoantibodies against erythrocytes lead to increased clearance of the erythrocytes, which in turn results in a potentially fatal hemolytic anemia. Depending on whether IgG or IgM antibodies are involved, response to therapy is different. Proper identification of the isotype of the anti-erythrocyte autoantibodies is, therefore, crucial. However, detection of IgM autoantibodies can be challenging. We, therefore, set out to improve the detection of anti-erythrocyte IgM. Direct detection using a flow cytometry-based approach did not yield satisfactory improvements. Next, we analyzed whether the presence of complement C3 on a patient's erythrocytes could be used for indirect detection of anti-erythrocyte IgM. To this end, we fractionated patients' sera by size exclusion chromatography and tested which fractions yielded complement deposition on erythrocytes. Strikingly, we found that all patients with C3 on their erythrocytes according to standard diagnostic tests had an IgM anti-erythrocyte component that could activate complement, even if no such autoantibody had been detected with any other test. This also included all tested patients with only IgG and C3 on their erythrocytes, who would previously have been classified as having an IgG-only mediated autoimmune hemolytic anemia. Depleting patients' sera of either IgG or IgM and testing the remaining complement activation confirmed this result. In conclusion, complement activation in autoimmune hemolytic anemia is mostly IgM-mediated and the presence of covalent C3 on patients' erythrocytes can be taken as a footprint of the presence of anti-erythrocyte IgM. Based on this finding, we propose a diagnostic workflow that will aid in choosing the optimal treatment strategy.

  13. Hyper IgM Syndrome with low IgM and thrombocytosis: an unusual case of immunodeficiency.

    Science.gov (United States)

    Yousef, Ejaz; Arshad Alvi, M

    2016-09-01

    We report a 5 years old male child with low serum IgG, IgA and IgM levels, who presented with recurrent perianal and oral ulcers, intermittent fever, and protracted diarrhea. Despite the lack of typical respiratory symptoms, low serum IgM level and persistent thrombocytosis, an X-linked hyper-IgM syndrome (X-HIGM) was considered. Laboratory investigations revealed a diagnosis of hyper-IgM syndrome caused by CD40L deficiency.

  14. Sunitinib-associated pseudothrombocytopenia induced by IgM antibody.

    Science.gov (United States)

    Albersen, Arjan; Porcelijn, Leendert; Schilders, Joyce; Zuetenhorst, Hanneke; Njo, Tjin; Hamberg, Paul

    2013-01-01

    Thrombocytopenia is a well-documented adverse reaction of sunitinib. Thrombocytopenia was observed in a patient with metastatic renal clear-cell carcinoma undergoing sunitinib treatment. Platelet count in an ethylenediaminetetraacetic acid (EDTA) sample was 19 × 10(9)/l. To exclude pseudothrombocytopenia (PTCP), a platelet count in citrate-anticoagulated blood was performed, showing a platelet count of 6 × 10(9)/l. Due to the apparent thrombocytopenia, the patient received platelet concentrates. Subsequent analyses revealed PTCP whereby platelet clumping was most abundant in citrate - followed by EDTA- and heparin-anticoagulated blood samples. This effect was partially reversed after placing blood samples at 37°C. The IgM antiplatelet autoantibodies responsible for in vitro agglutination are temperature and multianticoagulant dependent and did not react to amikacin pre-supplementation. Remarkably, the antibody revealed specificity to platelet antigens other than GPIIb/IIIa, GPIb/IX, GPIa/IIa, GPIV, and GPV. After 16 days of discontinuing sunitinib, no PTCP and no platelet reactive antibodies could be detected. We report a case of PTCP with clear time-relation with sunitinib, strongly suggesting the mechanism to be sunitinib dependent. Since this finding has not been described before, non-recognition of PTCP during sunitinib treatment might lead to dose reduction or unwarranted therapy.

  15. High affinity IgM(+) memory B cells are generated through a germinal center-dependent pathway.

    Science.gov (United States)

    Hara, Yasushi; Tashiro, Yasuyuki; Murakami, Akikazu; Nishimura, Miyuki; Shimizu, Takeyuki; Kubo, Masato; Burrows, Peter D; Azuma, Takachika

    2015-12-01

    During a T cell-dependent immune response, B cells undergo clonal expansion and selection and the induction of isotype switching and somatic hypermutation (SHM). Although somatically mutated IgM(+) memory B cells have been reported, it has not been established whether they are really high affinity B cells. We tracked (4-hydroxy-3-nitrophenyl) acetyl hapten-specific GC B cells from normal immunized mice based on affinity of their B cell receptor (BCR) and performed BCR sequence analysis. SHM was evident by day 7 postimmunization and increased with time, such that high affinity IgM(+) as well as IgG(+) memory B cells continued to be generated up to day 42. In contrast, class-switch recombination (CSR) was almost completed by day 7 and then the ratio of IgG1(+)/IgM(+) GC B cells remained unchanged. Together these findings suggest that IgM(+) B cells undergo SHM in the GC to generate high affinity IgM(+) memory cells and that this process continues even after CSR is accomplished.

  16. Serum IgM levels against select marine bacteria in the Atlantic sharpnose shark (Rhizoprionodon terraenovae) from three estuaries.

    Science.gov (United States)

    Karsten, A H; Rice, C D

    2006-07-01

    The Atlantic sharpnose shark (Rhizoprionodon terraenovae) is abundant and easily captured throughout the southeastern United States. Therefore this species serves as an ideal model for generating basic immunological reagents to establish baseline information regarding the immunophysiology of sharks in the wild, and for attempting to correlate shark immune responses to potential pathogens with the quality of the habitat in which they reside. Sharpnose shark serum IgM was purified over a protein-A column and used to generate mouse polyclonal anti-sera to develop indirect ELISAs for quantifying bacteria-specific IgM antibody titers against Vibrio anguillarium, Vibrio cholerae, Vibrio parahaemolyticus, Vibrio charchariae, Escherichia coli, Mycobacterium fortuitum, and Mycobacterium marinum. Serum samples from Atlantic sharpnose sharks were collected in Charleston, SC, Beaufort, SC, and New Brunswick, GA estuaries during the early summer, and again from Charleston, SC in the fall of the same year. Relative antibody titers against E. coli, V. anguillarium, and V. parahaemolyticus differed among the three sampling locations, suggesting differences in microbial abundance or immunological responses in sharks from three locations. Overall, antibody titers in Charleston, SC sharks increased between summer and fall. A combination of chronic exposure to specific bacteria and increased antibody responses due to elevated water temperatures are likely responsible for elevated specific IgM in these sharks sampled in the fall. To our knowledge, this is the first study to examine IgM responses in elasmobranchs collected directly from their habitat.

  17. B cells from knock-in mice expressing broadly neutralizing HIV antibody b12 carry an innocuous B cell receptor responsive to HIV vaccine candidates.

    Science.gov (United States)

    Ota, Takayuki; Doyle-Cooper, Colleen; Cooper, Anthony B; Doores, Katherine J; Aoki-Ota, Miyo; Le, Khoa; Schief, William R; Wyatt, Richard T; Burton, Dennis R; Nemazee, David

    2013-09-15

    Broadly neutralizing Abs against HIV protect from infection, but their routine elicitation by vaccination has not been achieved. To generate small animal models to test vaccine candidates, we have generated targeted transgenic ("knock-in") mice expressing, in the physiological Ig H and L chain loci, two well-studied broadly neutralizing Abs: 4E10, which interacts with the membrane proximal external region of gp41, and b12, which binds to the CD4 binding site on gp120. 4E10HL mice are described in the companion article (Doyle-Cooper et al., J. Immunol. 191: 3186-3191). In this article, we describe b12 mice. B cells in b12HL mice, in contrast to the case in 4E10 mice, were abundant and essentially monoclonal, retaining the b12 specificity. In cell culture, b12HL B cells responded avidly to HIV envelope gp140 trimers and to BCR ligands. Upon transfer to wild-type recipients, b12HL B cells responded robustly to vaccination with gp140 trimers. Vaccinated b12H mice, although generating abundant precursors and Abs with affinity for Env, were unable to rapidly generate neutralizing Abs, highlighting the importance of developing Ag forms that better focus responses to neutralizing epitopes. The b12HL and b12H mice should be useful in optimizing HIV vaccine candidates to elicit a neutralizing response while avoiding nonprotective specificities.

  18. Whole-body inhalation exposure to 1-bromopropane suppresses the IgM response to sheep red blood cells in female B6C3F1 mice and Fisher 344/N rats.

    Science.gov (United States)

    Anderson, Stacey E; Munson, Albert E; Butterworth, Leon F; Germolec, Dori; Morgan, Daniel L; Roycroft, Joseph A; Dill, Jeffrey; Meade, B J

    2010-02-01

    1-Bromopropane (1-BP) is categorized as a high-production-volume chemical and is currently used in the manufacture of pharmaceuticals, pesticides, and other chemicals. Its usage is estimated to be around 5 million pounds per year, resulting in the potential for widespread exposure in the workplace. Case reports and animal studies have suggested exposure to this compound may cause adverse reproductive and neurological effects. Using a battery of immunological assays, the immunotoxicity of 1-BP after whole body inhalation exposure in both mice and rats was evaluated. Significant decreases in the spleen immunoglobulin (Ig) M response to sheep red blood cells (SRBC) were observed in both mice (125-500 ppm) and rats (1000 ppm) after exposure to 1-BP for 10 wk. In addition, total spleen cells and T cells were significantly decreased after approximately 4 wk of 1-BP exposure in both mice (125-500 ppm) and rats (1000 ppm). No change in natural killer (NK) cell activity was observed. The observed alterations in spleen cellularity, phenotypic subsets, and impairment of humoral immune function across species raise further concern about human exposure to 1-BP and demonstrate the need for additional investigations into potential adverse health effects.

  19. A dengue DNA vaccine formulated with Vaxfectin® is well tolerated, and elicits strong neutralizing antibody responses to all four dengue serotypes in New Zealand white rabbits.

    Science.gov (United States)

    Raviprakash, Kanakatte; Luke, Thomas; Doukas, John; Danko, Janine; Porter, Kevin; Burgess, Timothy; Kochel, Tadeusz

    2012-12-01

    A tetravalent DNA vaccine formulated with Vaxfectin adjuvant was shown to elicit high levels of neutralizing antibody against all four dengue virus serotypes (Porter et al., ( 16) ), warranting further testing in humans. In preparation for a phase 1 clinical testing, the vaccine and the adjuvant were manufactured under current good manufacturing practice guidelines. The formulated vaccine and the adjuvant were tested for safety and/or immunogenicity in New Zealand white rabbits using a repeat dose toxicology study. The formulated vaccine and the adjuvant were found to be well tolerated by the animals. Animals injected with formulated vaccine produced strong neutralizing antibody response to all four dengue serotypes.

  20. Hemodynamic responses in amygdala and hippocampus distinguish between aversive and neutral cues during Pavlovian fear conditioning in behaving rats.

    Science.gov (United States)

    McHugh, Stephen B; Marques-Smith, Andre; Li, Jennifer; Rawlins, J N P; Lowry, John; Conway, Michael; Gilmour, Gary; Tricklebank, Mark; Bannerman, David M

    2013-02-01

    Lesion and electrophysiological studies in rodents have identified the amygdala and hippocampus (HPC) as key structures for Pavlovian fear conditioning, but human functional neuroimaging studies have not consistently found activation of these structures. This could be because hemodynamic responses cannot detect the sparse neuronal activity proposed to underlie conditioned fear. Alternatively, differences in experimental design or fear levels could account for the discrepant findings between rodents and humans. To help distinguish between these alternatives, we used tissue oxygen amperometry to record hemodynamic responses from the basolateral amygdala (BLA), dorsal HPC (dHPC) and ventral HPC (vHPC) in freely-moving rats during the acquisition and extinction of conditioned fear. To enable specific comparison with human studies we used a discriminative paradigm, with one auditory cue [conditioned stimulus (CS)+] that was always followed by footshock, and another auditory cue (CS-) that was never followed by footshock. BLA tissue oxygen signals were significantly higher during CS+ than CS- trials during training and early extinction. In contrast, they were lower during CS+ than CS- trials by the end of extinction. dHPC and vHPC tissue oxygen signals were significantly lower during CS+ than CS- trials throughout extinction. Thus, hemodynamic signals in the amygdala and HPC can detect the different patterns of neuronal activity evoked by threatening vs. neutral stimuli during fear conditioning. Discrepant neuroimaging findings may be due to differences in experimental design and/or fear levels evoked in participants. Our methodology offers a way to improve translation between rodent models and human neuroimaging.

  1. The effects of ageing on the immune response to Schistosoma haematobium and hookworm by measuring circulating immune complexes, C3, IgG, IgA and IgM levels in residents of Omi dam area of Kogi State, Nigeria.

    Science.gov (United States)

    Oyeyinka, G O; Awogun, I A; Akande, T M; Awarun, J A; Arinola, O G; Salimonu, L S

    2003-09-01

    In this study, the effects of infestation (with Schistosoma haematobium or hookworm) during host ageing on the serum levels of circulating immune complexes (CIC), C3, IgG, IgA and IgM were examined in residents of Omi dam area of Kogi state, Nigeria. S. haematobium-infested and hookworm-infested individuals showed no significant alteration in the levels of CIC, C3, IgG, IgA and IgM in comparison with controls. These levels were the same in infested subjects and controls even when the patients were pooled. Infested old people had the same concentrations of serum CIC, C3 IgG and IgM in comparison with infested young people but IgA levels were higher in the aged group (t=2.100; P0.20) was observed in the overall population of infested subjects; and infestation in old age did not alter CIC, C3, IgG, IgA and IgM levels in comparison with uninfested young people. For the uninfested, IgG, IgA and IgM values were similar in the aged and the young but the levels of CIC were higher (t=2.156; P0.10) in the aged. The results of this study suggest that the elevated CIC levels found in old people is age-related; and that the contribution of parasitic infestation to these raised levels is uncertain.

  2. HIV-1 Env DNA vaccine plus protein boost delivered by EP expands B- and T-cell responses and neutralizing phenotype in vivo.

    Directory of Open Access Journals (Sweden)

    Kar Muthumani

    Full Text Available An effective HIV vaccine will most likely require the induction of strong T-cell responses, broadly neutralizing antibodies (bNAbs, and the elicitation of antibody-dependent cellular cytotoxicity (ADCC. Previously, we demonstrated the induction of strong HIV/SIV cellular immune responses in macaques and humans using synthetic consensus DNA immunogens delivered via adaptive electroporation (EP. However, the ability of this improved DNA approach to prime for relevant antibody responses has not been previously studied. Here, we investigate the immunogenicity of consensus DNA constructs encoding gp140 sequences from HIV-1 subtypes A, B, C and D in a DNA prime-protein boost vaccine regimen. Mice and guinea pigs were primed with single- and multi-clade DNA via EP and boosted with recombinant gp120 protein. Sera were analyzed for gp120 binding and induction of neutralizing antibody activity. Immunization with recombinant Env protein alone induced low-titer binding antibodies with limited neutralization breath. In contrast, the synthetic DNA prime-protein boost protocol induced significantly higher antibody binding titers. Furthermore, sera from DNA prime-protein boost groups were able to neutralize a broader range of viruses in a panel of tier 1 clade B viruses as well as multiple tier 1 clade A and clade C viruses. Further investigation of synthetic DNA prime plus adaptive EP plus protein boost appears warranted.

  3. Dermographism (mechanical urticaria) mediated by IgM.

    Science.gov (United States)

    Horiko, T; Aoki, T

    1984-11-01

    Sera of three patients with symptomatic mechanical urticaria caused an immediate weal and flare reaction when injected intracutaneously into related recipients, and serum of one patient caused the same reaction in his own skin. Pretreatment of test skin sites with Compound 48/80 abolished or greatly reduced the reaction. This weal-producing substance was found in the same fraction as IgM in Sephadex G-200 gel filtration, was stable to heat treatment (56 degrees C, 4 h) and labile to 2-mercaptoethanol treatment. An immunoadsorption study using anti-IgM serum identified this weal-producing substance as IgM.

  4. Brain activity in response to Trauma-specific, Negative and Neutral stimuli. A fMRI study of recent Road Traffic Accident Survivors

    Directory of Open Access Journals (Sweden)

    Andre Sevenius Nilsen

    2016-08-01

    Full Text Available Most studies of neuro-functional patterns in trauma-exposed individuals have been conducted considerable time after the traumatic event. Hence little is known about neurofunctional processing shortly after trauma-exposure. We investigated brain activity patterns in response to trauma reminders as well as neutral and negative stimuli in individuals who had recently (within 3 weeks been involved in a Road Traffic Accident (RTA.Twenty-three RTA survivors and 17 non-trauma-exposed Healthy Controls (HC underwent functional MRI while viewing Trauma-specific, Negative and Neutral pictures. Data were analyzed from four a-priori Regions of Interest (ROI, including bilateral amygdala, subcallosal cortex, and medial prefrontal cortex. In addition, we performed a whole brain analysis and functional connectivity analysis during stimulus presentation.For both groups, Negative stimuli elicited more activity in the amygdala bilaterally than did Neutral and Trauma-specific stimuli. The whole brain analysis revealed higher activation in sensory processing related areas (bilateral occipital and temporal cortices and thalamus as well as frontal and superior parietal areas, for the RTA group compared to HC, for Trauma-specific stimuli contrasted with Neutral stimuli. We also observed higher functional connectivity for Trauma-Specific stimuli, between bilateral amygdala and somatosensory areas, for the RTA group compared to controls, when contrasted with Neutral stimuli. We argue that these results might indicate an attentional sensory processing bias towards Trauma-specific stimuli for trauma exposed individuals, a result in line with findings from the PTSD literature.

  5. Neutralizing Antibody Response and Antibody-Dependent Cellular Cytotoxicity in HIV-1-Infected Individuals from Guinea-Bissau and Denmark

    DEFF Research Database (Denmark)

    Borggren, Marie; Jensen, Sanne Skov; Heyndrickx, Leo

    2016-01-01

    cytotoxicity (ADCC) against local and nonlocal circulating HIV-1 strains. The neutralizing activity did not demonstrate higher potential against local circulating strains according to geography and subtype determination, but the plasma from Danish individuals demonstrated significantly higher inhibitory...

  6. Generation of a novel high-affinity monoclonal antibody with conformational recognition epitope on human IgM.

    Science.gov (United States)

    Sarikhani, Sina; Mirshahi, Manouchehr; Gharaati, Mohammad Reza; Mirshahi, Tooran

    2010-11-01

    As IgM is the first isotype of antibody which appears in blood after initial exposure to a foreign antigen in the pattern of primary response, detection, and quantification of this molecule in blood seems invaluable. To approach these goals, generation, and characterization of a highly specific mAb (monoclonal antibody) against human IgM were investigated. Human IgM immunoglobulins were used to immunize Balb/c mice. Spleen cells taken from the immunized animals were fused with SP2/O myeloma cells using PEG (polyethylene glycol, MW 1450) as fusogen. The hybridomas were cultured in HAT containing medium and supernatants from the growing hybrids were screened by enzyme-linked immunosorbent assay (ELISA) using plates coated with pure human IgM and the positive wells were then cloned at limiting dilutions. The best clone designated as MAN-1, was injected intraperitoneally to some Pristane-injected mice. Anti-IgM mAb was purified from the animals' ascitic fluid by protein-G sepharose followed by DEAE-cellulose ion exchange chromatography. MAN-1 interacted with human IgM with a very high specificity and affinity. The purity of the sample was tested by SDS-PAGE and the affinity constant was measured (K(a) = 3.5 x 10(9)M(-1). Immunoblotting and competitive ELISA were done and the results showed that the harvested antibody recognizes a conformational epitope on the mu chain of human IgM and there was no cross-reactivity with other subclasses of immunoglobulins. Furthermore, isotyping test was done and the results showed the subclass of the obtained mAb which was IgG(1)kappa.

  7. Antibody Production in Response to Staphylococcal MS-1 Phage Cocktail in Patients Undergoing Phage Therapy

    OpenAIRE

    Maciej Żaczek; Marzanna Łusiak-Szelachowska; Ewa Jończyk-Matysiak; Beata Weber-Dąbrowska; Ryszard Międzybrodzki; Barbara Owczarek; Agnieszka Kopciuch; Wojciech Fortuna; Paweł Rogóż; Andrzej Górski

    2016-01-01

    In this study, we investigated the humoral immune response (through the release of IgG, IgA, and IgM antiphage antibodies) to a staphylococcal phage cocktail in patients undergoing experimental phage therapy at the Phage Therapy Unit, Medical Center of the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy in Wrocław, Poland. We also evaluated whether occurring antiphage antibodies had neutralizing properties towards applied phages (K rate). Among 20 examined patients receiving...

  8. Recipients of vaccine against the 1976 "swine flu" have enhanced neutralization responses to the 2009 novel H1N1 influenza virus.

    Science.gov (United States)

    McCullers, Jonathan A; Van De Velde, Lee-Ann; Allison, Kim J; Branum, Kristen C; Webby, Richard J; Flynn, Patricia M

    2010-06-01

    BACKGROUND. The world is facing a novel H1N1 influenza pandemic. A pandemic scare with a similar influenza virus in 1976 resulted in the vaccination of nearly 45 million persons. We hypothesized that prior receipt of the 1976 "swine flu" vaccine would enhance immune responses to the 2009 novel H1N1 influenza strain. METHODS. A prospective, volunteer sample of employees aged > or = 55 years at a children's cancer hospital in August 2009 was assessed for antibody responses to the 2009 pandemic H1N1 influenza virus and the 2008-2009 seasonal H1N1 influenza virus. RESULTS. Antibody responses by hemagglutination-inhibition assay were high against both the seasonal influenza virus (89.7% had a titer considered seroprotective) and pandemic H1N1 influenza virus (88.8% had a seroprotective titer). These antibodies were effective at neutralizing the seasonal H1N1 influenza virus in 68.1% of participants (titer > or = 40), but only 18.1% had detectable neutralizing titers against the pandemic H1N1 influenza virus. Of 116 participants, 46 (39.7%) received the 1976 "swine flu" vaccine. Receipt of this vaccine significantly enhanced neutralization responses; 8 (17.4%) of 46 vaccine recipients had titers > or = 160, compared with only 3 (4.3%) of 70 who did not receive the vaccine (P = .018 by chi(2) test). CONCLUSIONS. In this cohort, persons aged > or = 55 years had evidence of robust immunity to the 2008-2009 seasonal H1N1 influenza virus. These antibodies were cross-reactive but nonneutralizing against the 2009 pandemic H1N1 influenza strain. Receipt of a vaccine to a related virus significantly enhanced the neutralization capacity of these responses, suggesting homologous vaccination against the 2009 pandemic H1N1 influenza virus would have a similar effect.

  9. A multi-subunit Chlamydia vaccine inducing neutralizing antibodies and strong IFN-γ(+) CMI responses protects against a genital infection in minipigs

    DEFF Research Database (Denmark)

    Bøje, Sarah; Olsen, Anja Weinreich; Erneholm, Karin;

    2016-01-01

    in vitro. Both Hirep1+CTH93/CAF01 and UV-SvD/CAF01 vaccination protected pigs against a vaginal C. trachomatis SvD infection. In conclusion, the Hirep1+CTH93/CAF01 vaccine proved highly immunogenic and equally protective as UV-SvD/CAF01 showing promise for the development of a subunit vaccine against......Chlamydia is the most widespread sexually transmitted bacterial disease and a prophylactic vaccine is highly needed. Ideally, this vaccine is required to induce a combined response of Th1 cell-mediated immune (CMI) response in concert with neutralizing antibodies. Using a novel Göttingen minipig...... animal model, we evaluated the immunogenicity and efficacy of a multi-subunit vaccine formulated in the strong Th1-inducing adjuvant CAF01. We evaluated a mixture of two fusion proteins (Hirep1 and CTH93) designed to promote either neutralizing antibodies or cell-mediated immunity, respectively. Hirep1...

  10. Anger and Sadness in Response to an Emotionally-Neutral Film: Evidence for Age-Specific Associations with Well-Being

    OpenAIRE

    Haase, Claudia M.; Seider, Benjamin H.; Shiota, Michelle N.; Levenson, Robert W.

    2011-01-01

    When the association between emotion and well-being is being considered, positive emotions usually come to mind. However, negative emotions serve important adaptive functions and particular negative emotions may be especially adaptive at different stages of adult development. We examined the associations between self-reported negative emotions in response to an emotionally-neutral, thematically-ambiguous film and subjective well-being among 76 young (age 20–29), 73 middle-aged (age 40–49), an...

  11. A reassessment of IgM memory subsets in humans

    Science.gov (United States)

    Bagnara, Davide; Squillario, Margherita; Kipling, David; Mora, Thierry; Walczak, Aleksandra M.; Da Silva, Lucie; Weller, Sandra; Dunn-Walters, Deborah K.; Weill, Jean-Claude; Reynaud, Claude-Agnès

    2015-01-01

    From paired blood and spleen samples from three adult donors we performed high-throughput V-h sequencing of human B-cell subsets defined by IgD and CD27 expression: IgD+CD27+ (“MZ”), IgD−CD27+(“memory”, including IgM (“IgM-only”), IgG and IgA) and IgD−CD27− cells (“double-negative”, including IgM, IgG and IgA). 91,294 unique sequences clustered in 42,670 clones, revealing major clonal expansions in each of these subsets. Among these clones, we further analyzed those shared sequences from different subsets or tissues for Vh-gene mutation, H-CDR3-length, and Vh/Jh usage, comparing these different characteristics with all sequences from their subset of origin, for which these parameters constitute a distinct signature. The IgM-only repertoire profile differed notably from that of MZ B cells by a higher mutation frequency, and lower Vh4 and higher Jh6 gene usage. Strikingly, IgM sequences from clones shared between the MZ and the memory IgG/IgA compartments showed a mutation and repertoire profile of IgM-only and not of MZ B cells. Similarly, all IgM clonal relationships (between MZ, IgM-only, and double-negative compartments) involved sequences with the characteristics of IgM-only B cells. Finally, clonal relationships between tissues suggested distinct recirculation characteristics between MZ and switched B cells. The “IgM-only” subset (including cells with its repertoire signature but higher IgD or lower CD27 expression levels) thus appear as the only subset showing precursor-product relationships with CD27+ switched memory B cells, indicating that they represent germinal center-derived IgM memory B cells, and that IgM memory and MZ B cells constitute two distinct entities. PMID:26355154

  12. Isolation and Characterization of IgM and IgY Antibodies from Plasma of Magellanic Penguins (Spheniscus magellanicus).

    Science.gov (United States)

    Bizelli, Camila C; Silva, A Sandriana R; da Costa, Jessica D; Vanstreels, Ralph E T; Atzingen, Marina V; Santoro, Marcelo L; Fernandes, Irene; Catão-Dias, José L; Faquim-Mauro, Eliana L

    2015-03-01

    Infectious diseases such as aspergillosis, avian malaria, and viral infections are significant threats to the conservation of penguins, leading to morbidity and mortality of these birds both in captivity and in the wild. The immune response to such infectious diseases is dependent on different mechanisms mediated by cells and soluble components such as antibodies. Antibodies or immunoglobulins are glycoproteins that have many structural and functional features that mediate distinct effector immune functions. Three distinct classes of antibodies have been identified in birds: immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin Y (IgY). In this study we aim to establish an efficient laboratory method to obtain IgM and IgY antibodies from plasma samples of healthy adult Magellanic penguins (Spheniscus magellanicus). The protocol was developed combining plasma delipidation, sequential precipitation with caprylic acid and ammonium sulfate, and size-exclusion chromatography. The efficiency of the protocol and the identity of the purified IgM and IgY antibodies were confirmed through enzyme-linked immunosorbent assay, Western blotting, one-dimensional and two-dimensional polyacrylamide gel electrophoresis, and lectin binding assay. Structural and physicochemical properties of IgM and IgY from Magellanic penguins were consistent with those of other avian species. This purification protocol will allow for more detailed studies on the humoral immunity of penguins and for the development of high specificity serologic assays to test Magellanic penguins for infectious pathogens.

  13. Early preservation of CXCR5+ PD-1+ helper T cells and B cell activation predict the breadth of neutralizing antibody responses in chronic HIV-1 infection.

    Science.gov (United States)

    Cohen, Kristen; Altfeld, Marcus; Alter, Galit; Stamatatos, Leonidas

    2014-11-01

    Much is known about the characteristics of broadly neutralizing antibodies (bNAbs) generated during HIV-1 infection, but little is known about immunological mechanisms responsible for their development in only a minority of those infected by HIV-1. By monitoring longitudinally a cohort of HIV-1-infected subjects, we observed that the preservation of CXCR5(+) CD4(+) T helper cell frequencies and activation status of B cells during the first year of infection correlates with the maximum breadth of plasma neutralizing antibody responses during chronic infection independently of viral load. Although, during the first year of infection, no differences were observed in the abilities of peripheral CXCR5(+) CD4(+) T helper cells to induce antibody secretion by autologous naive B cells, higher frequencies of class-switched antibodies were detected in cocultures of CXCR5(+) CD4(+) T and B cells from the subjects who later developed broadly neutralizing antibody responses than those who did not. Furthermore, B cells from the former subjects had higher expression of AICDA than B cells from the latter subjects, and transcript levels correlated with the frequency of CXCR5(+) CD4(+) T cells. Thus, the early preservation of CXCR5(+) CD4(+) T cells and B cell function are central to the development of bNAbs. Our study provides a possible explanation for their infrequent generation during HIV-1 infection. Broadly neutralizing antibodies are developed by HIV-1-infected subjects, but so far (and despite intensive efforts over the past 3 decades) they have not been elicited by immunization. Understanding how bNAbs are generated during natural HIV-1 infection and why only some HIV-1-infected subjects generate such antibodies will assist our efforts to elicit bNAbs by immunization. CXCR5(+) PD-1(+) CD4(+) T cells are critical for the development of high-affinity antigen-specific antibody responses. In our study, we found that the HIV-1-infected subjects who develop bNAbs have a higher

  14. Thermal diffusion in the IGM of clusters of galaxies

    CERN Document Server

    Shtykovskiy, P

    2009-01-01

    We revisit the phenomenon of elements diffusion in the intergalactic medium (IGM) in clusters of galaxies. The diffusion is driven by gravity, concentration and temperature gradients. The latter cause thermal diffusion, which has been so far ignored in IGM studies. We consider the full problem based on the Burgers' equations and demonstrate that the temperature gradients present in clusters of galaxies may successfully compete with gravity, evacuating metals from cooler regions. Under the combined action of gravity and temperature gradients, complicated metallicity profiles with several peaks and depressions may be formed. For a typical cool core cluster, the thermal diffusion may significantly reduce and even reverse the gravitational sedimentation of metals, resulting in the depression in their abundance in the core. This may have implications for diagnostics of the low temperature plasma in the centers of clusters of galaxies.

  15. DNA prime and virus-like particle boost from a single H5N1 strain elicits broadly neutralizing antibody responses against head region of H5 hemagglutinin.

    Science.gov (United States)

    Wang, Guiqin; Zhou, Fan; Buchy, Philippe; Zuo, Teng; Hu, Hongxing; Liu, Jingjing; Song, Yufeng; Ding, Heng; Tsai, Cheguo; Chen, Ze; Zhang, Linqi; Deubel, Vincent; Zhou, Paul

    2014-03-01

    Since 1996, highly pathogenic avian influenza (HPAI) H5N1 virus has presented a persistent threat to public health. Its high degree of genetic diversity also poses enormous challenges in developing effective vaccines. To search for vaccine regimens that could elicit broadly neutralizing antibody responses against diverse HPAI H5N1 strains, in the present study we tested H5 hemagglutinin (HA) from an A/Thailand/1(KAN)-1/2004 strain in a heterologous prime-boost vaccination. We demonstrated that priming mice with DNA and boosting with virus-like particle induced antibody responses that cross-neutralize all reported clades and subclades of HPAI H5N1 viruses and protect mice from high lethal dose HPAI H5N1 challenge in both active and passive immunizations. Unexpectedly, cross-divergent H5 neutralizing antibodies are directed to the HA head and block both attachment and postattachment of virus entry. Thus, we conclude that as a promising pan-H5 vaccine candidate this prime-boost regimen could be further developed in ferrets and in humans.

  16. Broader HIV-1 neutralizing antibody responses induced by envelope glycoprotein mutants based on the EIAV attenuated vaccine

    Directory of Open Access Journals (Sweden)

    Liu Lianxing

    2010-09-01

    Full Text Available Abstract Background In order to induce a potent and cross-reactive neutralizing antibody (nAb, an effective envelope immunogen is crucial for many viral vaccines, including the vaccine for the human immunodeficiency virus (HIV. The Chinese equine infectious anemia virus (EIAV attenuated vaccine has controlled the epidemic of this virus after its vaccination in over 70 million equine animals during the last 3 decades in China. Data from our past studies demonstrate that the Env protein of this vaccine plays a pivotal role in protecting horses from both homologous and heterogeneous EIAV challenges. Therefore, the amino acid sequence information from the Chinese EIAV attenuated vaccine, in comparison with the parental wild-type EIAV strains, was applied to modify the corresponding region of the envelope glycoprotein of HIV-1 CN54. The direction of the mutations was made towards the amino acids conserved in the two EIAV vaccine strains, distinguishing them from the two wild-type strains. The purpose of the modification was to enhance the immunogenicity of the HIV Env. Results The induced nAb by the modified HIV Env neutralized HIV-1 B and B'/C viruses at the highest titer of 1:270. Further studies showed that a single amino acid change in the C1 region accounts for the substantial enhancement in induction of anti-HIV-1 neutralizing antibodies. Conclusions This study shows that an HIV envelope modified by the information of another lentivirus vaccine induces effective broadly neutralizing antibodies. A single amino acid mutation was found to increase the immunogenicity of the HIV Env.

  17. Cross-reactive neutralizing antibody responses to enterovirus 71 infections in young children: implications for vaccine development.

    Directory of Open Access Journals (Sweden)

    Mei-Liang Huang

    Full Text Available BACKGROUND: Recently, enterovirus 71 (EV71 has caused life-threatening outbreaks involving neurological and cardiopulmonary complications in Asian children with unknown mechanism. EV71 has one single serotype but can be phylogenetically classified into 3 main genogroups (A, B and C and 11 genotypes (A, B1∼B5 and C1∼C5. In Taiwan, nationwide EV71 epidemics with different predominant genotypes occurred in 1998 (C2, 2000-2001 (B4, 2004-2005 (C4, and 2008 (B5. In this study, sera were collected to measure cross-reactive neutralizing antibody titers against different genotypes. METHODS: We collected historical sera from children who developed an EV71 infection in 1998, 2000, 2005, 2008, or 2010 and measured cross-reactive neutralizing antibody titers against all 11 EV71 genotypes. In addition, we aligned and compared the amino acid sequences of P1 proteins of the tested viruses. RESULTS: Serology data showed that children infected with genogroups B and C consistently have lower neutralizing antibody titers against genogroup A (>4-fold difference. The sequence comparisons revealed that five amino acid signatures (N143D in VP2; K18R, H116Y, D167E, and S275A in VP1 are specific for genogroup A and may be related to the observed antigenic variations. CONCLUSIONS: This study documented antigenic variations among different EV71 genogroups and identified potential immunodominant amino acid positions. Enterovirus surveillance and vaccine development should monitor these positions.

  18. IFN-γ-producing CD4+ T cells promote generation of protective germinal center-derived IgM+ B cell memory against Salmonella Typhi.

    Science.gov (United States)

    Perez-Shibayama, Christian; Gil-Cruz, Cristina; Pastelin-Palacios, Rodolfo; Cervantes-Barragan, Luisa; Hisaki, Emiliano; Chai, Qian; Onder, Lucas; Scandella, Elke; Regen, Tommy; Waisman, Ari; Isibasi, Armando; Lopez-Macias, Constantino; Ludewig, Burkhard

    2014-06-01

    Abs play a significant role in protection against the intracellular bacterium Salmonella Typhi. In this article, we investigated how long-term protective IgM responses can be elicited by a S. Typhi outer-membrane protein C- and F-based subunit vaccine (porins). We found that repeated Ag exposure promoted a CD4(+) T cell-dependent germinal center reaction that generated mutated IgM-producing B cells and was accompanied by a strong expansion of IFN-γ-secreting T follicular helper cells. Genetic ablation of individual cytokine receptors revealed that both IFN-γ and IL-17 are required for optimal germinal center reactions and production of porin-specific memory IgM(+) B cells. However, more profound reduction of porin-specific IgM B cell responses in the absence of IFN-γR signaling indicated that this cytokine plays a dominant role. Importantly, mutated IgM mAbs against porins exhibited bactericidal capacity and efficiently augmented S. Typhi clearance. In conclusion, repeated vaccination with S. Typhi porins programs type I T follicular helper cell responses that contribute to the diversification of B cell memory and promote the generation of protective IgM Abs.

  19. IgM nephropathy: Clinical picture and pathological findings in 36 patients

    Directory of Open Access Journals (Sweden)

    Ghadeer A Mokhtar

    2011-01-01

    Full Text Available Immunoglobulin M nephropathy (IgMN is an idiopathic glomerulonephritis characterized by a variable degree of mesangial hyper- cellularity and diffuse IgM deposits. This study describes the clinical presentation and the morphological findings in 36 patients, five adults and 31 children, with IgMN. The initial manifestations of the disease were the nephrotic syndrome in 32 patients, proteinuria in two, hematuria associated with proteinuria in 16 and isolated recurrent gross hematuria in two patients. The nephrotic syndrome was steroid responsive in 9% of the cases, steroid dependent in 25% and steroid resistant in 66%. Five patients were hypertensive at the onset of the disease. The mean follow- up period was 3.4 years (range, 1-7 years. One patient developed end- stage kidney disease five years after the diagnosis. On light microscopy, 24 specimens showed mild focal and segmental mesangial hyper- cellularity, 10 cases were normal in cellularity and two cases showed diffuse global mesangial hyper- cellularity. Four cases showed focal and segmental glomerulosclerosis. Mild interstitial inflammation and fibrosis were observed in 11 cases and focal tubular atrophy and hypertensive hyaline arteriosclerosis were noted in three cases. In addition to IgM, the immunofluorescence study showed C3 deposits in 12 cases, IgG in nine cases and IgA in one case. Electron dense- deposits in the mesangium and para- mesangial areas were demonstrated on electron microscopy in 22 cases. In view of its different clinical presentations and the constant findings of diffuse mesangial IgM deposition in all the cases, it is concluded that this form of nephropathy constitutes a distinct entity separate from minimal change disease or focal and segmental glomerulosclerosis. Patients with IgMN had a higher prevalence of steroid resistance and dependence in the proteinuric group.

  20. Duration of secretory IgM and IgA antibodies to respiratory syncytial virus in a community study in Guinea-Bissau

    DEFF Research Database (Denmark)

    Stensballe, L G; Kofoed, P E; Nante, E J

    2000-01-01

    have therefore assessed the duration of secretory IgM and IgA antibody responses and whether assays for these antibodies can be used to improve the diagnosing of RSV-associated infections. During two RSV epidemics in Guinea-Bissau, 32 RSV antigen-positive children with LRI were followed with sequential...... nasopharyngeal suction on days 7, 14, 30, 60 and 120 in the first epidemic and every fortnight for 6 mo after the second epidemic to measure the duration of secretory IgM and IgA responses. Nearly all of the children had an IgM response during the first month after infection. The response ratio was highest...... phase of infection. A secondary response may be more likely in children with low IgM responses in the acute phase (RR = 2.08 (95% confidence interval (CI) 0.92-4.70)). The IgA response was highest on days 28 and 42 after antigen detection, 72% having a detectable IgA response within the first 1.5 mo...

  1. Duration of secretory IgM and IgA antibodies to respiratory syncytial virus in a community study in Guinea-Bissau

    DEFF Research Database (Denmark)

    Stensballe, L G; Kofoed, P E; Nante, E J

    2000-01-01

    have therefore assessed the duration of secretory IgM and IgA antibody responses and whether assays for these antibodies can be used to improve the diagnosing of RSV-associated infections. During two RSV epidemics in Guinea-Bissau, 32 RSV antigen-positive children with LRI were followed with sequential...... nasopharyngeal suction on days 7, 14, 30, 60 and 120 in the first epidemic and every fortnight for 6 mo after the second epidemic to measure the duration of secretory IgM and IgA responses. Nearly all of the children had an IgM response during the first month after infection. The response ratio was highest...... phase of infection. A secondary response may be more likely in children with low IgM responses in the acute phase (RR = 2.08 (95% confidence interval (CI) 0.92-4.70)). The IgA response was highest on days 28 and 42 after antigen detection, 72% having a detectable IgA response within the first 1.5 mo...

  2. Immunization of rabbits with highly purified, soluble, trimeric human immunodeficiency virus type 1 envelope glycoprotein induces a vigorous B cell response and broadly cross-reactive neutralization.

    Directory of Open Access Journals (Sweden)

    Gerald V Quinnan

    Full Text Available Previously we described induction of cross-reactive HIV-1 neutralizing antibody responses in rabbits using a soluble HIV-1 gp140 envelope glycoprotein (Env in an adjuvant containing monophosphoryl lipid A (MPL and QS21 (AS02A. Here, we compared different forms of the same HIV-1 strain R2 Env for antigenic and biophysical characteristics, and in rabbits characterized the extent of B cell induction for specific antibody expression and secretion and neutralizing responses. The forms of this Env that were produced in and purified from stably transformed 293T cells included a primarily dimeric gp140, a trimeric gp140 appended to a GCN4 trimerization domain (gp140-GCN4, gp140-GCN4 with a 15 amino acid flexible linker between the gp120 and gp41 ectodomain (gp140-GCN4-L, also trimeric, and a gp140 with the flexible linker purified from cell culture supernatants as either dimer (gp140-L(D or monomer (gp140-L(M. Multimeric states of the Env proteins were assessed by native gel electrophoresis and analytical ultracentrifugation. The different forms of gp140 bound broadly cross-reactive neutralizing (BCN human monoclonal antibodies (mAbs similarly in ELISA and immunoprecipitation assays. All Envs bound CD4i mAbs in the presence and absence of sCD4, as reported for the R2 Env. Weak neutralization of some strains of HIV-1 was seen after two additional doses in AS02A. Rabbits that were given a seventh dose of gp140-GCN4-L developed BCN responses that were weak to moderate, similar to our previous report. The specificity of these responses did not appear similar to that of any of the known BCN human mAbs. Induction of spleen B cell and plasma cells producing immunoglobulins that bound trimeric gp140-GCN4-L was vigorous, based on ELISpot and flow cytometry analyses. The results demonstrate that highly purified gp140-GCN4-L trimer in adjuvant elicits BCN responses in rabbits accompanied by vigorous B cell induction.

  3. Neutralizing Antibody Response and Efficacy of Novel Recombinant Tetravalent Dengue DNA Vaccine Comprising Envelope Domain III in Mice

    Directory of Open Access Journals (Sweden)

    Ajit Kulkarni

    2017-03-01

    Full Text Available Background: Dengue is a global arboviral threat to humans; causing 390 million infections per year. The availability of safe and effective tetravalent dengue vaccine is a global requirement to prevent epidemics, morbidity, and mortality associated with it. Methods: Five experimental groups (6 mice per group each of 5-week-old BALB/c mice were immunized with vaccine and placebo (empty plasmid (100 µg, i.m. on days 0, 14 and 28. Among these, four groups (one group per serotype of each were subsequently challenged 3 weeks after the last boost with dengue virus (DENV serotypes 1-4 (100 LD50, 20 µl intracerebrally to determine vaccine efficacy. The fifth group of each was used as a control. The PBS immunized group was used as mock control. Serum samples were collected before and after subsequent immunizations. EDIII fusion protein expression was determined by Western blot. Total protein concentration was measured by Bradford assay. Neutralizing antibodies were assessed by TCID50-CPE inhibition assay. Statistical analysis was performed using Stata/IC 10.1 software for Windows. One-way repeated measures ANOVA and Mann-Whitney test were used for neutralizing antibody analysis and vaccine efficacy, respectively. Results: The recombinant EDIII fusion protein was expressed adequately in transfected 293T cells. Total protein concentration was almost 3 times more than the control. Vaccine candidate induced neutralizing antibodies against all four DENV serotypes with a notable increase after subsequent boosters. Vaccine efficacy was 83.3% (DENV-1, -3, -4 and 50% (DENV-2. Conclusion: Our results suggest that vaccine is immunogenic and protective; however, further studies are required to improve the immunogenicity particularly against DENV-2.

  4. Humoral response and neutralization capacity of sheep serum inoculated with natural and Cobalt 60-irradiated Crotalus durissus terrificus venom (Laurenti, 1768)

    Energy Technology Data Exchange (ETDEWEB)

    Netto, D.P.; Alfieri, A.A. [Universidade Estadual de Londrina, PR (Brazil). Centro de Ciencias Agrarias, Dept. de Medicina Veterinaria Preventiva; Chiacchio, S.B.; Bicudo, P.L. [UNESP, SP (Brazil). Faculdade de Medicina Veterinaria e Zootecnia; Nascimento, N. [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil). Supervisao de Radiobiologia]. E-mail: rnetto@uel.br

    2002-07-01

    The aim of this work was to investigate antigen irradiation on crotalic antivenom and the capacity of sheep as serum producers. Twelve sheep in two groups of six were inoculated with Crotalus durissus terrificus venom. One group was inoculated with natural venom (N V) and the other with Cobalt 60 gamma-irradiated venom (Ir V). Three antigen doses were given to the animals at monthly intervals for immunization. The toxic activity of the venom was assessed by LD 50 determination in mice. Blood samples were collected weekly analyses of serum neutralization capacity and potency. At the end of the experiment, the animals were challenged with a LD 50 for sheep showed no signs of envenoming. These results showed that toxicity of the irradiated venom was 4.4 times less than the natural venom. The sera from the irradiated group neutralized LD 50 14.6 times, and the sera from the natural group 4.4 times. Sera from the irradiated group were five times more potent. The two groups did not present clinical alterations. The results of this study show the potential for using sheep in crotalic antivenom production. The use of irradiated venom in sheep immunization induces a powerful and lasting humoral immune response shown by both the in vitro neutralization and potency tests and by the indirect ELISA antibody level detection technique. (author)

  5. A multi-subunit Chlamydia vaccine inducing neutralizing antibodies and strong IFN-γ+ CMI responses protects against a genital infection in minipigs

    Science.gov (United States)

    Bøje, Sarah; Olsen, Anja Weinreich; Erneholm, Karin; Agerholm, Jørgen Steen; Jungersen, Gregers; Andersen, Peter; Follmann, Frank

    2016-01-01

    Chlamydia is the most widespread sexually transmitted bacterial disease and a prophylactic vaccine is highly needed. Ideally, this vaccine is required to induce a combined response of Th1 cell-mediated immune (CMI) response in concert with neutralizing antibodies. Using a novel Göttingen minipig animal model, we evaluated the immunogenicity and efficacy of a multi-subunit vaccine formulated in the strong Th1-inducing adjuvant CAF01. We evaluated a mixture of two fusion proteins (Hirep1 and CTH93) designed to promote either neutralizing antibodies or cell-mediated immunity, respectively. Hirep1 is a novel immunogen based on the variant domain (VD) 4 region from major outer membrane protein (MOMP) serovar (Sv) D, SvE and SvF, and CTH93 is a fusion molecule of three antigens (CT043, CT414 and MOMP). Pigs were immunized twice intramuscularly with either Hirep1+CTH93/CAF01, UV-inactivated Chlamydia trachomatis SvD bacteria (UV-SvD/CAF01) or CAF01. The Hirep1+CTH93/CAF01 vaccine induced a strong CMI response against the vaccine antigens and high titers of antibodies, particularly against the VD4 region of MOMP. Sera from Hirep1+CTH93/CAF01 immunized pigs neutralized C. trachomatis SvD and SvF infectivity in vitro. Both Hirep1+CTH93/CAF01 and UV-SvD/CAF01 vaccination protected pigs against a vaginal C. trachomatis SvD infection. In conclusion, the Hirep1+CTH93/CAF01 vaccine proved highly immunogenic and equally protective as UV-SvD/CAF01 showing promise for the development of a subunit vaccine against Chlamydia. PMID:26268662

  6. A multi-subunit Chlamydia vaccine inducing neutralizing antibodies and strong IFN-γ⁺ CMI responses protects against a genital infection in minipigs.

    Science.gov (United States)

    Bøje, Sarah; Olsen, Anja Weinreich; Erneholm, Karin; Agerholm, Jørgen Steen; Jungersen, Gregers; Andersen, Peter; Follmann, Frank

    2016-02-01

    Chlamydia is the most widespread sexually transmitted bacterial disease and a prophylactic vaccine is highly needed. Ideally, this vaccine is required to induce a combined response of Th1 cell-mediated immune (CMI) response in concert with neutralizing antibodies. Using a novel Göttingen minipig animal model, we evaluated the immunogenicity and efficacy of a multi-subunit vaccine formulated in the strong Th1-inducing adjuvant CAF01. We evaluated a mixture of two fusion proteins (Hirep1 and CTH93) designed to promote either neutralizing antibodies or cell-mediated immunity, respectively. Hirep1 is a novel immunogen based on the variant domain (VD) 4 region from major outer membrane protein (MOMP) serovar (Sv) D, SvE and SvF, and CTH93 is a fusion molecule of three antigens (CT043, CT414 and MOMP). Pigs were immunized twice intramuscularly with either Hirep1+CTH93/CAF01, UV-inactivated Chlamydia trachomatis SvD bacteria (UV-SvD/CAF01) or CAF01. The Hirep1+CTH93/CAF01 vaccine induced a strong CMI response against the vaccine antigens and high titers of antibodies, particularly against the VD4 region of MOMP. Sera from Hirep1+CTH93/CAF01 immunized pigs neutralized C. trachomatis SvD and SvF infectivity in vitro. Both Hirep1+CTH93/CAF01 and UV-SvD/CAF01 vaccination protected pigs against a vaginal C. trachomatis SvD infection. In conclusion, the Hirep1+CTH93/CAF01 vaccine proved highly immunogenic and equally protective as UV-SvD/CAF01 showing promise for the development of a subunit vaccine against Chlamydia.

  7. Natural IgM Switches the Function of Lipopolysaccharide-Activated Murine Bone Marrow-Derived Dendritic Cells to a Regulatory Dendritic Cell That Suppresses Innate Inflammation.

    Science.gov (United States)

    Lobo, Peter I; Schlegel, Kailo H; Bajwa, Amandeep; Huang, Liping; Kurmaeva, Elvira; Wang, Binru; Ye, Hong; Tedder, Thomas F; Kinsey, Gilbert R; Okusa, Mark D

    2015-12-01

    We have previously shown that polyclonal natural IgM protects mice from renal ischemia/reperfusion injury (IRI) by inhibiting the reperfusion inflammatory response. We hypothesized that a potential mechanism involved IgM modulation of dendritic cells (DC), as we observed high IgM binding to splenic DC. To test this hypothesis, we pretreated bone marrow-derived DC (BMDC) with polyclonal murine or human IgM prior to LPS activation and demonstrated that 0.5 × 10(6) IgM/LPS-pretreated BMDC, when injected into wild-type C57BL/6 mice 24 h before renal ischemia, protect mice from developing renal IRI. We show that this switching of LPS-activated BMDC to a regulatory phenotype requires modulation of BMDC function that is mediated by IgM binding to nonapoptotic BMDC receptors. Regulatory BMDC require IL-10 and programmed death 1 as well as downregulation of CD40 and p65 NF-κB phosphorylation to protect in renal IRI. Blocking the programmed death ligand 1 binding site just before i.v. injection of IgM/LPS-pretreated BMDC or using IL-10 knockout BMDC fails to induce protection. Similarly, IgM/LPS-pretreated BMDC are rendered nonprotective by increasing CD40 expression and phosphorylation of p65 NF-κB. How IgM/LPS regulatory BMDC suppress in vivo ischemia-induced innate inflammation remains to be determined. However, we show that suppression is dependent on other in vivo regulatory mechanisms in the host, that is, CD25(+) T cells, B cells, IL-10, and circulating IgM. There was no increase in Foxp3(+) regulatory T cells in the spleen either before or after renal IRI. Collectively, these findings show that natural IgM anti-leukocyte Abs can switch BMDC to a regulatory phenotype despite the presence of LPS that ordinarily induces BMDC maturation.

  8. The response of human thermal sensation and its prediction to temperature step-change (cool-neutral-cool.

    Directory of Open Access Journals (Sweden)

    Xiuyuan Du

    Full Text Available This paper reports on studies of the effect of temperature step-change (between a cool and a neutral environment on human thermal sensation and skin temperature. Experiments with three temperature conditions were carried out in a climate chamber during the period in winter. Twelve subjects participated in the experiments simulating moving inside and outside of rooms or cabins with air conditioning. Skin temperatures and thermal sensation were recorded. Results showed overshoot and asymmetry of TSV due to the step-change. Skin temperature changed immediately when subjects entered a new environment. When moving into a neutral environment from cool, dynamic thermal sensation was in the thermal comfort zone and overshoot was not obvious. Air-conditioning in a transitional area should be considered to limit temperature difference to not more than 5°C to decrease the unacceptability of temperature step-change. The linear relationship between thermal sensation and skin temperature or gradient of skin temperature does not apply in a step-change environment. There is a significant linear correlation between TSV and Qloss in the transient environment. Heat loss from the human skin surface can be used to predict dynamic thermal sensation instead of the heat transfer of the whole human body.

  9. Induction of virus-neutralizing antibodies and T cell responses by dengue virus type 1 virus-like particles prepared from Pichia pastoris

    Institute of Scientific and Technical Information of China (English)

    TANG Yun-xia; JIANG Li-fang; ZHOU Jun-mei; YIN Yue; YANG Xiao-meng; LIU Wen-quan; FANG Dan-yun

    2012-01-01

    Background Dengue is currently a significant global health problem but no vaccines are available against the four dengue serotypes virus infections.The development of safe and effective vaccines has been hampered by the requirement of conferring complete protection against all four dengue serotypes and the lack of a convenient animal model.Virus-like particles (VLPs) have emerged as a promising subunit vaccine candidate.One strategy of vaccine development is to produce a tetravalent dengue subunit vaccine by mixing recombinant VLPs,corresponding to all four dengue virus serotypes.Towards this end,this study aimed to establish a Pichia pastoris (P.pastoris) expression system for production of dengue virus type 1 (DENV-1) VLPs and evaluate the humoral and cellular immune response of this particle in mice.Methods A recombinant yeast P.pastoris clone containing prM and E genes of DENV-1 was constructed and DENV-1 VLPs expressed by this clone were analyzed by sucrose density gradient centrifugation,Western blotting,and transmission electron microscope.Groups of mice were immunized by these particles plus adjuvant formulations,then mice were tested by ELISA and neutralization assay for humoral immune response,and by lymphocyte proliferation and cytokine production assays for a cellular immune response.Results Our data demonstrated that recombinant DENV-1 VLPs consisting of prM and E protein were successfully expressed in the yeast P.pastoris.Sera of VLPs immunized mice were shown to contain a high-titer of antibodies and the neutralization assay suggested that those antibodies neutralized virus infection in vitro.Data from the T lymphocyte proliferation assay showed proliferation of T cell,and ELISA found elevated secretion levels of interferon IFN-y and IL-4.Conclusions P.pastoris-expressed DENV-1 VLPs can induce virus neutralizing antibodies and T cell responses in immunized mice.Using P.pastoris to produce VLPs offers a promising and economic strategy for dengue virus

  10. The role of B-cells and IgM antibodies in parasitemia, anemia, and VSG switching in Trypanosoma brucei-infected mice.

    Directory of Open Access Journals (Sweden)

    Stefan Magez

    Full Text Available African trypanosomes are extracellular parasitic protozoa, predominantly transmitted by the bite of the haematophagic tsetse fly. The main mechanism considered to mediate parasitemia control in a mammalian host is the continuous interaction between antibodies and the parasite surface, covered by variant-specific surface glycoproteins. Early experimental studies have shown that B-cell responses can be strongly protective but are limited by their VSG-specificity. We have used B-cell (microMT and IgM-deficient (IgM(-/- mice to investigate the role of B-cells and IgM antibodies in parasitemia control and the in vivo induction of trypanosomiasis-associated anemia. These infection studies revealed that that the initial setting of peak levels of parasitemia in Trypanosoma brucei-infected microMT and IgM(-/- mice occurred independent of the presence of B-cells. However, B-cells helped to periodically reduce circulating parasites levels and were required for long term survival, while IgM antibodies played only a limited role in this process. Infection-associated anemia, hypothesized to be mediated by B-cell responses, was induced during infection in microMT mice as well as in IgM(-/- mice, and as such occurred independently from the infection-induced host antibody response. Antigenic variation, the main immune evasion mechanism of African trypanosomes, occurred independently from host antibody responses against the parasite's ever-changing antigenic glycoprotein coat. Collectively, these results demonstrated that in murine experimental T. brucei trypanosomiasis, B-cells were crucial for periodic peak parasitemia clearance, whereas parasite-induced IgM antibodies played only a limited role in the outcome of the infection.

  11. Evolution of the Humoral Response during HCV Infection: Theories on the Origin of Broadly Neutralizing Antibodies and Implications for Vaccine Design.

    Science.gov (United States)

    Murira, Armstrong; Lapierre, Pascal; Lamarre, Alain

    2016-01-01

    Similar to human immunodeficiency virus (HIV)-1, vaccine-induced elicitation of broadly neutralizing (bNt) antibodies (Abs) is gaining traction as a key goal toward the eradication of the hepatitis C virus (HCV) pandemic. Previously, the significance of the Ab response against HCV was underappreciated given the prevailing evidence advancing the role of the cellular immune response in clearance and overall control of the infection. However, recent findings have driven growing interest in the humoral arm of the immune response and in particular the role of bNt responses due to their ability to confer protective immunity upon passive transfer in animal models. Nevertheless, the origin and development of bNt Abs is poorly understood and their occurrence is rare as well as delayed with emergence only observed in the chronic phase of infection. In this review, we characterize the interplay between the host immune response and HCV as it progresses from the acute to chronic phase of infection. In addition, we place these events in the context of current hypotheses on the origin of bNt Abs against the HIV-1, whose humoral immune response is better characterized. Based on the increasing significance of the humoral immune response against HCV, characterization of these events may be critical in understanding the development of the bNt responses and, thus, provide strategies toward effective vaccine design.

  12. Understanding the IGM Absorbers with Numerical Simulations of the WHIM

    Science.gov (United States)

    Hallman, Eric

    2010-09-01

    The total baryon content of the universe can be deduced both from observations of the cosmic microwave background, and the observed Deuterium to Hydrogen ratio {D/H} through the theory of big-bang nucleosynthesis. Though observations can account for all of the baryons at high redshift, roughly half the baryons are referred to as``missing'' in the low redshift universe since they are not observed in known baryonic structureslike galaxies, clusters, and the Lyman-alpha forest. Cosmological simulations predict that the missing baryons can be found in acosmic web of sheets and filaments that thread the halos, in the ``warm-hot intergalactic medium'' {WHIM} phase {10^5 - 10^7K}. The WHIM gas should be detectable in Ly-alpha or Ly-beta {10^4 K gas} and in shock-heated gas{10^5 - 10^6 K} in Ly-alpha and OVI absorption. Ultraviolet {UV} spectroscopy with the Far Ultraviolet Spectroscopic Explorer {FUSE} and HST has detected IGM absorbers in various metal species and HI along lines of sight to bright quasars that are likely associated with gas in the WHIM phase. This gas may account for the bulk of the missing baryons in the low redshift universe. Using Enzo hydro/N-body grid-based cosmology simulations, we will determine whether there is a unique interpretation given the current IGM absorber observations, and how new observations may provide strong tests of these theories. We propose to, with a suite of high-resolution Enzo simulations and novel analysis techniques, characterize the UV absorbers, and to model observational metrics to compare with the data. In particular, we study the metal diffusion throughout the IGM using various prescriptions for star formation, galaxy formation and thermaland chemical feedback, and study the numerical convergence of these algorithms.

  13. Class switch recombination process in ataxia telangiectasia patients with elevated serum levels of IgM.

    Science.gov (United States)

    Mohammadinejad, Payam; Abolhassani, Hassan; Aghamohammadi, Asghar; Pourhamdi, Shabnam; Ghosh, Sujal; Sadeghi, Bamdad; Nasiri Kalmarzi, Rasoul; Durandy, Anne; Borkhardt, Arndt

    2015-01-01

    Ataxia telangiectasia (AT) is a rare primary immunodeficiency disorder with various clinical manifestations. Increased serum levels of IgM and recurrent infections, mainly sinopulmonary infections, can be the presenting feature in a number of AT patients and may be initially misdiagnosed as hyper-IgM (HIgM) syndrome. This study was designed to investigate class switch recombination (CSR) as a critical mechanism in B lymphocytes' maturation to produce different isotypes of antibody in response to antigen stimulation in AT cases with HIgM presentation. Quantitative IgE production after stimulation by IL-4 and CD40L was considered as an indicator for CSR function. We also compared their results with sex and age matched AT patients without HIgM presentation. We report four AT patients with recurrent infections during infancy and high serum levels of IgM. Laboratory evaluations revealed defective CSR while none of the three AT patients without HIgM presentation had a defect in the CSR process. The characterized defect in AT is a mutation in the ataxia telangiectasia mutated (ATM) gene. This gene may result in CSR defects due to impaired DNA break repair. A special association between AT and HIgM may indicate a new subgroup of AT patients according to their clinical phenotype and CSR condition.

  14. A hantavirus pulmonary syndrome (HPS) DNA vaccine delivered using a spring-powered jet injector elicits a potent neutralizing antibody response in rabbits and nonhuman primates.

    Science.gov (United States)

    Kwilas, Steve; Kishimori, Jennifer M; Josleyn, Matthew; Jerke, Kurt; Ballantyne, John; Royals, Michael; Hooper, Jay W

    2014-01-01

    Sin Nombre virus (SNV) and Andes virus (ANDV) cause most of the hantavirus pulmonary syndrome (HPS) cases in North and South America, respectively. The chances of a patient surviving HPS are only two in three. Previously, we demonstrated that SNV and ANDV DNA vaccines encoding the virus envelope glycoproteins elicit high-titer neutralizing antibodies in laboratory animals, and (for ANDV) in nonhuman primates (NHPs). In those studies, the vaccines were delivered by gene gun or muscle electroporation. Here, we tested whether a combined SNV/ANDV DNA vaccine (HPS DNA vaccine) could be delivered effectively using a disposable syringe jet injection (DSJI) system (PharmaJet, Inc). PharmaJet intramuscular (IM) and intradermal (ID) needle-free devices are FDA 510(k)-cleared, simple to use, and do not require electricity or pressurized gas. First, we tested the SNV DNA vaccine delivered by PharmaJet IM or ID devices in rabbits and NHPs. Both IM and ID devices produced high-titer anti-SNV neutralizing antibody responses in rabbits and NHPs. However, the ID device required at least two vaccinations in NHP to detect neutralizing antibodies in most animals, whereas all animals vaccinated once with the IM device seroconverted. Because the IM device was more effective in NHP, the Stratis(®) (PharmaJet IM device) was selected for follow-up studies. We evaluated the HPS DNA vaccine delivered using Stratis(®) and found that it produced high-titer anti-SNV and anti-ANDV neutralizing antibodies in rabbits (n=8/group) as measured by a classic plaque reduction neutralization test and a new pseudovirion neutralization assay. We were interested in determining if the differences between DSJI delivery (e.g., high-velocity liquid penetration through tissue) and other methods of vaccine injection, such as needle/syringe, might result in a more immunogenic DNA vaccine. To accomplish this, we compared the HPS DNA vaccine delivered by DSJI versus needle/syringe in NHPs (n=8/group). We found

  15. A Hantavirus Pulmonary Syndrome (HPS) DNA Vaccine Delivered Using a Spring-powered Jet Injector Elicits a Potent Neutralizing Antibody
Response in Rabbits and Nonhuman Primates

    Science.gov (United States)

    Kwilas, Steve; Kishimori, Jennifer M.; Josleyn, Matthew; Jerke, Kurt; Ballantyne, John; Royals, Michael; Hooper, Jay W.

    2014-01-01

    Sin Nombre virus (SNV) and Andes virus (ANDV) cause most of the hantavirus pulmonary syndrome (HPS) cases in North and South America, respectively. The chances of a patient surviving HPS are only two in three. Previously, we demonstrated that SNV and ANDV DNA vaccines encoding the virus envelope glycoproteins elicit high-titer neutralizing antibodies in laboratory animals, and (for ANDV) in nonhuman primates (NHPs). In those studies, the vaccines were delivered by gene gun or muscle electroporation. Here, we tested whether a combined SNV/ANDV DNA vaccine (HPS DNA vaccine) could be delivered effectively using a disposable syringe jet injection (DSJI) system (PharmaJet, Inc). PharmaJet intramuscular (IM) and intradermal (ID) needle-free devices are FDA 510(k)-cleared, simple to use, and do not require electricity or pressurized gas. First, we tested the SNV DNA vaccine delivered by PharmaJet IM or ID devices in rabbits and NHPs. Both IM and ID devices produced high-titer anti-SNV neutralizing antibody responses in rabbits and NHPs. However, the ID device required at least two vaccinations in NHP to detect neutralizing antibodies in most animals, whereas all animals vaccinated once with the IM device seroconverted. Because the IM device was more effective in NHP, the Stratis® (PharmaJet IM device) was selected for follow-up studies. We evaluated the HPS DNA vaccine delivered using Stratis® and found that it produced high-titer anti-SNV and anti-ANDV neutralizing antibodies in rabbits (n=8/group) as measured by a classic plaque reduction neutralization test and a new pseudovirion neutralization assay. We were interested in determining if the differences between DSJI delivery (e.g., high-velocity liquid penetration through tissue) and other methods of vaccine injection, such as needle/syringe, might result in a more immunogenic DNA vaccine. To accomplish this, we compared the HPS DNA vaccine delivered by DSJI versus needle/syringe in NHPs (n=8/group). We found that

  16. Coexistence of IgM antihepatitis A virus and IgM antihepatitis E virus in acute viral hepatitis: a prospective, multicentre study in Korea.

    Science.gov (United States)

    Jang, J-H; Jung, Y M; Kim, J S; Lee, S H; Kim, J-W; Hwang, S G; Rim, K S; Park, S J; Park, Y M; Kang, S-K; Lee, H S; Yun, H; Kim, J-H; Jeong, S-H

    2011-10-01

    This study investigated the clinical, serological and molecular characteristics of coexistence of both immunoglobulin M (IgM) antihepatitis A virus (HAV) and IgM antihepatitis E virus (HEV) in acute viral hepatitis using a prospective, multicentre design. Among a total of 771 symptomatic cases with acute viral hepatitis enrolled in a Korean city from September 2006 to August 2008, coexistence of IgM anti-HAV and IgM anti-HEV was found in 43 patients (A+E group; 6%), while the existence of IgM anti-HAV alone was found in 595 patients (A group; 77%) and that of IgM anti-HEV alone in 14 patients (E group; 2%). Clinical data analysis and measurement of IgM and IgG anti-HEV were performed using two different commercial kits, and HAV RNA and HEV RNA were detected in available serum or stool samples. The clinical features of the A+E group were similar to those of the A group. HAV RNA detection rates in the A+E and A group were similar, while HEV RNA was detected only in the stool samples of the E group, not in the A+E group. Comparative testing of anti-HEV using two different ELISA kits showed markedly discordant results for IgM anti-HEV positivity and consistently low positivity for IgG anti-HEV in the A+E group. Coexistence of IgM anti-HEV measured by the Genelabs ELISA kit in the setting of hepatitis A appears to yield false-positive results in nonendemic areas of HEV infection. Diagnosis of hepatitis E using IgM anti-HEV should be made with caution.

  17. Growth performance, body lipid, brood amount, and rearing environment response to supplemental neutral phytase in zebrafish (Danio rerio) diet.

    Science.gov (United States)

    Liu, Liwei; Su, Jianmei; Liang, Xu-Fang; Luo, Yuliang

    2013-09-01

    The present study was to evaluate the effects of neutral phytase supplementation on growth performance, survival ratio (SR), body lipid, brood amount, and rearing environment in zebrafish. The control diet was not supplemented phytase, and three levels of phytase (500, 1000, or 1500 U kg(-1)) was added to the three other diets (named as PP500, PP1000, and PP1500). Triplicate groups (twelve 100-L tanks) of zebrafish (initial mean weight, 0.284±0.012 g) were fed twice daily (08:00 and 16:00 h) to satiation for 12 weeks. The results showed that supplemental phytase in the diet improved weight gain (60.49%, 86.63%, 99.06%, and 111.88% in control, PP500, PP1000, and PP1500) and the specific growth ratio of zebrafish (pzebrafish. The brood amounts (116, 123, and 124 eggs in PP500, PP1000, and PP1500) of fish fed with phytase-supplemented diets were little higher than the control (mean egg was 112). The ammonia-nitrogen concentration in water of fish fed with phytase-supplemented diet was significantly lower than the control. The nitrite concentration in water was also decreased in water of fish fed with phytase-supplemented diet. The SR was increased with the increasing of dietary phytase despite no significant difference was observed among each group. The present study first suggested that neutral phytase could be applied in the zebrafish diet. Furthermore, phytase addition increased the growth, body lipid, brood amount, and SR of zebrafish, and meanwhile decreased the ammonia-nitrogen and nitrite concentrations in rearing water.

  18. Induction of epitope-specific neutralizing antibodies against West Nile virus.

    Science.gov (United States)

    Oliphant, Theodore; Nybakken, Grant E; Austin, S Kyle; Xu, Qing; Bramson, Jonathan; Loeb, Mark; Throsby, Mark; Fremont, Daved H; Pierson, Theodore C; Diamond, Michael S

    2007-11-01

    Previous studies have established that an epitope on the lateral ridge of domain III (DIII-lr) of West Nile virus (WNV) envelope (E) protein is recognized by strongly neutralizing type-specific antibodies. In contrast, an epitope against the fusion loop in domain II (DII-fl) is recognized by flavivirus cross-reactive antibodies with less neutralizing potential. Using gain- and loss-of-function E proteins and wild-type and variant WNV reporter virus particles, we evaluated the expression pattern and activity of antibodies against the DIII-lr and DII-fl epitopes in mouse and human serum after WNV infection. In mice, immunoglobulin M (IgM) antibodies to the DIII-lr epitope were detected at low levels at day 6 after infection. However, compared to IgG responses against other epitopes in DI and DII, which were readily detected at day 8, the development of IgG against DIII-lr epitope was delayed and did not appear consistently until day 15. This late time point is notable since almost all death after WNV infection in mice occurs by day 12. Nonetheless, at later time points, DIII-lr antibodies accumulated and comprised a significant fraction of the DIII-specific IgG response. In sera from infected humans, DIII-lr antibodies were detected at low levels and did not correlate with clinical outcome. In contrast, antibodies to the DII-fl were detected in all human serum samples and encompassed a significant percentage of the anti-E protein response. Our experiments suggest that the highly neutralizing DIII-lr IgG antibodies have little significant role in primary infection and that the antibody response of humans may be skewed toward the induction of cross-reactive, less-neutralizing antibodies.

  19. Induction of Epitope-Specific Neutralizing Antibodies against West Nile Virus▿

    Science.gov (United States)

    Oliphant, Theodore; Nybakken, Grant E.; Austin, S. Kyle; Xu, Qing; Bramson, Jonathan; Loeb, Mark; Throsby, Mark; Fremont, Daved H.; Pierson, Theodore C.; Diamond, Michael S.

    2007-01-01

    Previous studies have established that an epitope on the lateral ridge of domain III (DIII-lr) of West Nile virus (WNV) envelope (E) protein is recognized by strongly neutralizing type-specific antibodies. In contrast, an epitope against the fusion loop in domain II (DII-fl) is recognized by flavivirus cross-reactive antibodies with less neutralizing potential. Using gain- and loss-of-function E proteins and wild-type and variant WNV reporter virus particles, we evaluated the expression pattern and activity of antibodies against the DIII-lr and DII-fl epitopes in mouse and human serum after WNV infection. In mice, immunoglobulin M (IgM) antibodies to the DIII-lr epitope were detected at low levels at day 6 after infection. However, compared to IgG responses against other epitopes in DI and DII, which were readily detected at day 8, the development of IgG against DIII-lr epitope was delayed and did not appear consistently until day 15. This late time point is notable since almost all death after WNV infection in mice occurs by day 12. Nonetheless, at later time points, DIII-lr antibodies accumulated and comprised a significant fraction of the DIII-specific IgG response. In sera from infected humans, DIII-lr antibodies were detected at low levels and did not correlate with clinical outcome. In contrast, antibodies to the DII-fl were detected in all human serum samples and encompassed a significant percentage of the anti-E protein response. Our experiments suggest that the highly neutralizing DIII-lr IgG antibodies have little significant role in primary infection and that the antibody response of humans may be skewed toward the induction of cross-reactive, less-neutralizing antibodies. PMID:17715236

  20. Recognition of tumor antigens in 4T1 cells by natural IgM from three strains of mice with different susceptibilities to spontaneous breast cancer

    Science.gov (United States)

    Díaz-Zaragoza, Mariana; Hernández-Ávila, Ricardo; Ostoa-Saloma, Pedro

    2017-01-01

    The issue of antibody responses to tumors is potentially important to cancer immunologists. Early detection of cancer represents one of the most promising approaches to reduce the growing cancer burden. Natural immunoglobulin (Ig)M antibodies have been associated with the recognition and elimination of cancerous and precancerous cells. Using natural IgM antibodies, the present study identified a set of antigens in healthy mice from three different strains and examined whether the global patterns of antibodies are able to discriminate between a condition of more or less susceptibility to breast cancer. The current study performed two-dimensional (2D) immunoblotting to detect antigens from 4T1 cells using natural IgM from serum of healthy female mice from three different strains. The t-test was used to analyze the total number of spots. There were no significant differences in the numbers of antigens recognized in each strain. However, differences in patterns were observed on 2D immunoblots among the three strains. The reactivity patterns of natural IgM antibodies to particular antigens exhibited non-random clustering, which discriminated between strains with different susceptibilities to spontaneous breast cancer. The results demonstrated that the patterns of reactivity to defined subsets of antigens are able to provide information regarding differential diagnosis associated with breast cancer sensitivity. Therefore, it may be concluded that it is possible to segregate the IgM humoral immune response toward cancer antigens according to the genetic background of individuals. In addition, it is possible to identify the recognized antigens that allow grouping or discriminate between the different IgM antibodies expressed. The possible association between a particular antigen and cancer susceptibility requires further study, but the methodology exposed in the present study may identify potential candidates for this possible association.

  1. A functional study of low molecular weight IgM from patients with autoimmune disease

    Institute of Scientific and Technical Information of China (English)

    HUI JUN ZHOU; XIAO PING YANG; WAN SHENG CHEN; PETER ROBERTS THOMSON; HU JI XU

    2006-01-01

    High levels of low molecular weight (LMW) IgM in certain diseases are associated with clinical and laboratory indices which reflect the severity of the disease. These associations suggest that LMW IgM may play an important role in the immunopathogenesis of these diseases. To further approach the question concerning the functional activity of LMW IgM in disease, a panel of LMW IgM and high molecular weight (HMW) IgM preparations with or without rheumatoid factor (RF) activity were used to investigate their antibody binding activity and their effector function. It was found that LMW IgM-RF and HMW IgM-RF had a similar binding capacity to Fc fragment as there was no significant difference in the affinity index between them. It further showed that the rate of activation and total amount of utilization of complement by LMW IgM and HMW IgM was similar, although the mean fluorescence of C3 deposition by IgM-RF and HMW IgM-RF was slightly higher than that of LMW IgM-RF and other control RF antibodies. However, the current study demonstrated that LMW IgM had strong neutrophil activating properties when compared with HMW IgM. These findings suggest that one mechanism of LMW IgM contributing to the immunopathogenesis of RA may be due to the formation of circulating immune complex (CIC) by LMW IgM with subsequent activation of neutrophils. Whether LMW IgM has other functional activity in disease is unclear and needs further investigation.

  2. Cytomegalovirus IgM Seroprevalence among Women of Reproductive Age in the United States.

    Science.gov (United States)

    Wang, Chengbin; Dollard, Sheila C; Amin, Minal M; Bialek, Stephanie R

    2016-01-01

    Cytomegalovirus (CMV) IgM indicates recent active CMV infection. CMV IgM seroprevalence is a useful marker for prevalence of transmission. Using data from the National Health and Nutrition Examination Survey (NHANES) III 1988-1994, we present estimates of CMV IgM prevalence by race/ethnicity, provide a comparison of IgM seroprevalence among all women and among CMV IgG positive women, and explore factors possibly associated with IgM seroprevalence, including socioeconomic status and exposure to young children. There was no difference in IgM seroprevalence by race/ethnicity among all women (3.1%, 2.2%, and 1.6% for non-Hispanic white, non-Hispanic black and Mexican American, respectively; P = 0.11). CMV IgM seroprevalence decreased significantly with increasing age in non-Hispanic black women (Pwomen (P = 0.07), while no apparent trend with age was seen in non-Hispanic white women (P = 0.99). Among 4001 IgG+ women, 118 were IgM+, resulting in 4.9% IgM seroprevalence. In IgG+ women, IgM seroprevalence varied significantly by age (5.3%, 7.3%, and 3.7% for women of 12-19, 20-29, and 30-49 years; P = 0.04) and race/ethnicity (6.1%, 2.7%, and 2.0% for non-Hispanic white, non-Hispanic black, and Mexican American; P<0.001). The factors reported associated with IgG seroprevalence were not associated with IgM seroprevalence. The patterns of CMV IgM seroprevalence by age, race/ethnicity, and IgG serostatus may help understanding the epidemiology of congenital CMV infection as a consequence of vertical transmission and are useful for identifying target populations for intervention to reduce CMV transmission.

  3. Natural and adaptive IgM antibodies in the recognition of tumor-associated antigens of breast cancer (Review)

    Science.gov (United States)

    DÍAZ-ZARAGOZA, MARIANA; HERNÁNDEZ-ÁVILA, RICARDO; VIEDMA-RODRÍGUEZ, RUBÍ; ARENAS-ARANDA, DIEGO; OSTOA-SALOMA, PEDRO

    2015-01-01

    For early detection of cancer, education and screening are important, but the most critical factor is the development of early diagnostic tools. Methods that recognize the warning signs of cancer and take prompt action lead to an early diagnosis; simple tests can identify individuals in a healthy population who have the disease but have not developed symptoms. Early detection of cancer is significant and is one of the most promising approaches by which to reduce the growing cancer burden and guide curative treatment. The early diagnosis of patients with breast cancer is challenging, since it is the most common cancer in women worldwide. Despite the advent of mammography in screening for breast cancer, low-resource, low-cost alternative tools must be implemented to complement mammography findings. IgM is part of the first line of defense of an organism and is responsible for recognizing and eliminating infectious particles and removing transformed cells. Most studies on breast cancer have focused on the development of IgG-like molecules as biomarkers or as a treatment for the advanced stages of cancer, but autoantibodies (IgM) and tumor-associated antigens (proteins or carbohydrates with aberrant structures) have not been examined as early diagnostic tools for breast cancer. The present review summarizes the function of natural and adaptive IgM in eliminating cancer cells in the early stages of pathology and their value as early diagnostic tools. IgM, as a component of the immune system, is being used to identify tumor-associated antigens and tumor-associated carbohydrate antigens. PMID:26133558

  4. DNA vaccine molecular adjuvants SP-D-BAFF and SP-D-APRIL enhance anti-gp120 immune response and increase HIV-1 neutralizing antibody titers.

    Science.gov (United States)

    Gupta, Sachin; Clark, Emily S; Termini, James M; Boucher, Justin; Kanagavelu, Saravana; LeBranche, Celia C; Abraham, Sakhi; Montefiori, David C; Khan, Wasif N; Stone, Geoffrey W

    2015-04-01

    the gp120 trimer, the inaccessibility of the conserved sequences, highly variable protein sequences, and the loss of HIV-1-specific antibody-producing cells during development. We have shown previously that tumor necrosis factor (TNF) superfamily ligands, including BAFF and APRIL, can be multitrimerized using the lung protein SP-D (surfactant protein D), enhancing immune responses. Here we show that DNA or DNA-protein vaccines encoding BAFF or APRIL multitrimers, IL-12p70, and membrane-bound HIV-1 Env gp140 induced tier 1 and tier 2 neutralizing antibodies in a mouse model. BAFF and APRIL enhanced the immune reaction, improved antibody binding, and increased the numbers of anti-HIV-1 antibody-secreting cells. Adaptation of this vaccine design may prove useful in designing preventive HIV-1 vaccines for humans. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  5. Investigation Of The Diffuse IGM By Cross-Correlation Studies

    Science.gov (United States)

    Farnsworth, Damon; Brown, Shea; Rudnick, Lawrence

    2009-12-01

    We present results from the first cross-correlation search for the synchrotron component of the diffuse intergalactic medium (IGM) in filamentary large scale structure (LSS). We used the low resolution (36') Bonn survey at 21cm, with the infrared 2MASS catalog as a tracer of the LSS. Synchrotron emission likely results from LSS formation shocks and feedback from AGN and galactic winds [2]. We determined 3σ upper limits to the diffuse emission in units of flux per galaxy; these correspond to filament equipartition magnetic fields as low as 0.2 μG. The detection threshold for the average (peak) filament brightness is 1 (7) mK for 0.03Bonn survey, demonstrating the power of this technique.

  6. Effect of temperature and season on reproduction, neutral red retention and metallothionein responses of earthworms exposed to metals in field soils

    Energy Technology Data Exchange (ETDEWEB)

    Svendsen, Claus [Centre for Ecology and Hydrology, Monks Wood, Abbots Ripton, Huntingdon, Cambridgeshire PE28 2LS (United Kingdom)]. E-mail: csv@ceh.ac.uk; Hankard, Peter K. [Centre for Ecology and Hydrology, Monks Wood, Abbots Ripton, Huntingdon, Cambridgeshire PE28 2LS (United Kingdom)]. E-mail: pkh@ceh.ac.uk; Lister, Lindsay J. [Centre for Ecology and Hydrology, Monks Wood, Abbots Ripton, Huntingdon, Cambridgeshire PE28 2LS (United Kingdom)]. E-mail: llist@ceh.ac.uk; Fishwick, Samantha K. [Environment Agency, Block 1 Government Buildings, Burghill Road, Westbury-on-Trym, Bristol BS10 6BF (United Kingdom)]. E-mail: samantha.fishwick@environment-agency.gov.uk; Jonker, Martijs J. [Centre for Ecology and Hydrology, Monks Wood, Abbots Ripton, Huntingdon, Cambridgeshire PE28 2LS (United Kingdom)]. E-mail: mjonker@science.uva.nl; Spurgeon, David J. [Centre for Ecology and Hydrology, Monks Wood, Abbots Ripton, Huntingdon, Cambridgeshire PE28 2LS (United Kingdom)]. E-mail: dasp@ceh.ac.uk

    2007-05-15

    This study investigated the short-term survival, reproduction and physiological (lysosomal membrane stability, metallothionein transcript copy number, body tissue metal concentrations) responses of Lumbricus rubellus exposed to metal contaminated field soils under different laboratory temperatures (10, 15 and 20 {sup o}C) and physiological responses of earthworms collected from the field in three different seasons (spring, autumn, winter). In the laboratory, metal contaminated soils had significant effects on reproduction (p < 0.001), metallothionein-2 (MT-2) expression (p = 0.033) and earthworm As (p = 0.003), Cd (p = 0.001), Pb (p < 0.001) and Zn (p < 0.001) concentration, but not lysosomal membrane stability and tissue Hg and Cu. No effect of temperature was found for any parameter. Principal component analysis of extractable and tissue metal concentrations indicated PC1 as a measure of metal stress. Both cocoon production (r = - 0.75) and MT-2 induction (r = 0.41) were correlated with PC1. A correlation was also found between cocoon production and MT-2 expression (r = - 0.41). Neutral red retention and MT-2 measurements in worms collected from the field sites in three seasons confirmed the absence of a temperature effect on these responses. - Laboratory and field studies demonstrate metal effects on earthworm life-cycle and biochemical responses are not influenced by temperature regime.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  8. A rapid immunization strategy with a live attenuated tetravalent dengue vaccine elicits protective neutralizing antibody responses in non-human primates

    Directory of Open Access Journals (Sweden)

    Yuping eAmbuel

    2014-06-01

    Full Text Available Dengue viruses (DENVs cause approximately 390 million cases of DENV infections annually and over 3 billion people worldwide are at risk of infection. No dengue vaccine is currently available nor is there an antiviral therapy for DENV infections. We have developed a tetravalent live-attenuated DENV vaccine (TDV that consists of a molecularly characterized attenuated DENV-2 strain (TDV-2 and three chimeric viruses containing the pre-membrane and envelope genes of DENV-1, -3 and -4 expressed in the context of the TDV-2 genome. To impact dengue vaccine delivery in endemic areas and immunize travelers, a simple and rapid immunization strategy (RIS is preferred. We investigated RIS consisting of two full vaccine doses being administered subcutaneously or intradermally on the initial vaccination visit (day 0 at two different anatomical locations with a needle-free disposable syringe jet injection (DSJI delivery devices (PharmaJet in non-human primates (NHP. This vaccination strategy resulted in efficient priming and induction of neutralizing antibody responses to all four DENV serotypes comparable to those elicited by the traditional prime and boost (two months later vaccination schedule. In addition, the vaccine induced CD4+ and CD8+ T cells producing IFN-γ, IL-2, and TNF-α, and targeting the DENV-2 NS1, NS3 and NS5 proteins. Moreover, vaccine-specific T cells were cross-reactive with the non-structural NS3 and NS5 proteins of DENV-4. When animals were challenged with DENV-2 they were protected with no detectable viremia, and exhibited sterilizing immunity (no increase of neutralizing titers post- challenge. RIS could decrease vaccination visits and provide quick immune response to all four DENV serotypes. This strategy could increase vaccination compliance and would be especially advantageous for travelers into endemic areas.

  9. Neutralizing Antibody Response after Intramuscular Purified Vero Cell Rabies Vaccination (PVRV in Iranian Patients with Specific Medical Conditions.

    Directory of Open Access Journals (Sweden)

    Pooneh Rahimi

    Full Text Available Post exposure prophylaxis using one of the WHO-approved vaccines is the method of choice for preventing rabies. Abnormal immune function in patients with some specific medical conditions, such as pregnancy, chronic hepatitis B virus infection, different types of cancers like lymphoma, diabetes I and II, corticosteroid consumption by patients with rheumatoid arthritis and lupus erythematosus, could impair the immunologic response to various vaccines. The immune response to rabies vaccination has never been examined in patients with any of these described medical conditions. This study purposed to evaluate the neutralyzing antibody response after vaccination with purified Vero cell rabies vaccine (PVRV according to the WHO-recommended Post-Exposure Prophylaxis (PEP "ESSEN" regimen.Thirty healthy volunteers and 50 volunteers with different medical conditions who were exposed to a suspected rabid animal in the 2nd or 3rd category of exposure received 5 doses of PVRV under the ESSEN protocol. Three blood samples were collected on days 0 (before the first dose, 14, and 35. The anti-rabies antibody titer was measured using the Rapid Fluorescent Foci Inhibition Test (RFFIT and an ELISA Bio-Rad, Platelia, Rabies II kit.All subjects reached NAb titers above 0.5 IU/ml by day 14 after vaccination. On day 35 (1 week after receiving the last rabies vaccine, anti-rabies antibodies were in the protective level (>0.5 IU/ml in both groups. There was no statistically significant difference in anti-rabies antibody response due to the type of exposure (category 2 or 3, and successful seroconversion was confirmed in both groups.In conclusion, the ESSEN protocol using the PVRV vaccine is sufficient for rabies prophylaxis in patients with specific medical conditions.

  10. Differential Antibody Responses to Conserved HIV-1 Neutralizing Epitopes in the Context of Multivalent Scaffolds and Native-Like gp140 Trimers

    Science.gov (United States)

    Morris, Charles D.; Azadnia, Parisa; de Val, Natalia; Vora, Nemil; Honda, Andrew; Giang, Erick; Saye-Francisco, Karen; Cheng, Yushao; Lin, Xiaohe; Mann, Colin J.; Tang, Jeffrey; Sok, Devin; Burton, Dennis R.; Law, Mansun; Ward, Andrew B.

    2017-01-01

    ABSTRACT Broadly neutralizing antibodies (bNAbs) have provided valuable insights into the humoral immune response to HIV-1. While rationally designed epitope scaffolds and well-folded gp140 trimers have been proposed as vaccine antigens, a comparative understanding of their antibody responses has not yet been established. In this study, we probed antibody responses to the N332 supersite and the membrane-proximal external region (MPER) in the context of heterologous protein scaffolds and native-like gp140 trimers. Ferritin nanoparticles and fragment crystallizable (Fc) regions were utilized as multivalent carriers to display scaffold antigens with grafted N332 and MPER epitopes, respectively. Trimeric scaffolds were also identified to stabilize the MPER-containing BG505 gp140.681 trimer in a native-like conformation. Following structural and antigenic evaluation, a subset of scaffold and trimer antigens was selected for immunization in BALB/c mice. Serum binding revealed distinct patterns of antibody responses to these two bNAb targets presented in different structural contexts. For example, the N332 nanoparticles elicited glycan epitope-specific antibody responses that could also recognize the native trimer, while a scaffolded BG505 gp140.681 trimer generated a stronger and more rapid antibody response to the trimer apex than its parent gp140.664 trimer. Furthermore, next-generation sequencing (NGS) of mouse splenic B cells revealed expansion of antibody lineages with long heavy-chain complementarity-determining region 3 (HCDR3) loops upon activation by MPER scaffolds, in contrast to the steady repertoires primed by N332 nanoparticles and a soluble gp140.664 trimer. These findings will facilitate the future development of a coherent vaccination strategy that combines both epitope-focused and trimer-based approaches. PMID:28246356

  11. Between detection and neutralization.

    Energy Technology Data Exchange (ETDEWEB)

    Snell, Mark Kamerer; Green, Mary Wilson; Adams, Douglas Glenn; Pritchard, Daniel Allison

    2005-08-01

    Security system analytical performance analysis is generally based on the probability of system effectiveness. The probability of effectiveness is a function of the probabilities of interruption and neutralization. Interruption occurs if the response forces are notified in sufficient time to engage the adversary. Neutralization occurs if the adversary attack is defeated after the security forces have actively engaged the adversary. Both depend upon communications of data. This paper explores details of embedded communications functions that are often assumed to be inconsequential. It is the intent of the authors to bring focus to an issue in security system modeling that, if not well understood, has the potential to be a deciding factor in the overall system failure or effectiveness.

  12. What is Neutrality?

    NARCIS (Netherlands)

    Pierik, R.; van der Burg, W.

    2014-01-01

    This paper reinvestigates the question of liberal neutrality. We contend that current liberal discussions have been dominated - if not hijacked - by one particular interpretation of what neutrality could imply, namely, exclusive neutrality, that aims to exclude religious and cultural expressions

  13. The long elusive IgM Fc receptor, FcμR.

    Science.gov (United States)

    Kubagawa, Hiromi; Oka, Satoshi; Kubagawa, Yoshiki; Torii, Ikuko; Takayama, Eiji; Kang, Dong-Won; Jones, Dewitt; Nishida, Naonori; Miyawaki, Toshio; Bertoli, Luigi F; Sanders, Sheila K; Honjo, Kazuhito

    2014-07-01

    IgM exists as both a monomer on the surface of B cells and a pentamer secreted by plasma cells. Both pre-immune "natural" and antigen-induced "immune" IgM antibodies are important for protective immunity and for immune regulation of autoimmune processes by recognizing pathogens and self-antigens. Effector proteins interacting with the Fc portion of IgM, such as complement and complement receptors, have thus far been proposed but fail to fully account for the IgM-mediated protection and regulation. A major reason for this deficit in our understanding of IgM function seems to be lack of data on a long elusive Fc receptor for IgM (FcμR). We have recently identified a bona fide FcμR in both humans and mice. In this article we briefly review what we have learned so far about FcμR.

  14. A Single 17D Yellow Fever Vaccination Provides Lifelong Immunity; Characterization of Yellow-Fever-Specific Neutralizing Antibody and T-Cell Responses after Vaccination.

    Directory of Open Access Journals (Sweden)

    Rosanne W Wieten

    Full Text Available Prompted by recent amendments of Yellow Fever (YF vaccination guidelines from boost to single vaccination strategy and the paucity of clinical data to support this adjustment, we used the profile of the YF-specific CD8+ T-cell subset profiles after primary vaccination and neutralizing antibodies as a proxy for potentially longer lasting immunity.PBMCs and serum were collected in six individuals on days 0, 3, 5, 12, 28 and 180, and in 99 individuals >10 years after YF-vaccination. Phenotypic characteristics of YF- tetramer+ CD8+ T-cells were determined using class I tetramers. Antibody responses were measured using a standardized plaque reduction neutralization test (PRNT. Also, characteristics of YF-tetramer positive CD8+ T-cells were compared between individuals who had received a primary- and a booster vaccination. YF-tetramer+ CD8+ T-cells were detectable on day 12 (median tetramer+ cells as percentage of CD8+ T-cells 0.2%, range 0.07-3.1%. On day 180, these cells were still present (median 0.06%, range 0.02-0.78%. The phenotype of YF-tetramer positive CD8+ T-cells shifted from acute phase effector cells on day 12, to late differentiated or effector memory phenotype (CD45RA-/+CD27- on day 28. Two subsets of YF-tetramer positive T-cells (CD45RA+CD27- and CD45RA+CD27+ persisted until day 180. Within all phenotypic subsets, the T-bet: Eomes ratio tended to be high on day 28 after vaccination and shifted towards predominant Eomes expression on day 180 (median 6.0 (day 28 vs. 2.2 (day 180 p = 0.0625, suggestive of imprinting compatible with long-lived memory properties. YF-tetramer positive CD8+ T-cells were detectable up to 18 years post vaccination, YF-specific antibodies were detectable up to 40 years after single vaccination. Booster vaccination did not increase titers of YF-specific antibodies (mean 12.5 vs. 13.1, p = 0.583, nor induce frequencies or alter phenotypes of YF-tetramer+ CD8+ T-cells.The presence of a functionally competent YF

  15. A recombinant mimetics of the HIV-1 gp41 prehairpin fusion intermediate fused with human IgG Fc fragment elicits neutralizing antibody response in the vaccinated mice

    Energy Technology Data Exchange (ETDEWEB)

    Qi, Zhi; Pan, Chungen; Lu, Hong; Shui, Yuan [Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065 (United States); Li, Lin [Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065 (United States); School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515 (China); Li, Xiaojuan; Xu, Xueqing; Liu, Shuwen [School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515 (China); Jiang, Shibo, E-mail: sjiang@nybloodcenter.org [Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065 (United States); School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515 (China)

    2010-07-30

    Research highlights: {yields} One recombinant mimetics of gp41 prehairpin fusion intermediate (PFI) consisting of gp41 N46 sequence, foldon and IgG Fc, designated N46FdFc, was expressed. {yields} N46FdFc-induced antibodies in mice that neutralized HIV-1 infection, inhibited PIE7 binding to PFI, blocked gp41 six-helix bundle formation, and suppressed HIV-1 mediated cell-cell fusion. {yields} These findings provide an important clue for developing recombinant gp41 PFI mimetics-based HIV vaccines. -- Abstract: HIV-1 gp41 prehairpin fusion intermediate (PFI) composed of three N-terminal heptad repeats (NHR) plays a crucial role in viral fusion and entry and represents an attractive target for anti-HIV therapeutics (e.g., enfuvirtide) and vaccines. In present study, we constructed and expressed two recombinant gp41 PFI mimetics, designated N46Fd and N46FdFc. N46Fd consists of N46 (residues 536-581) in gp41 NHR and foldon (Fd), a trimerization motif. N46FdFc is composed of N46Fd fused with human IgG Fc fragment as an immunoenhancer. We immunized mice with N46 peptide, N46Fd and N46FdFc, respectively, and found that only N46FdFc elicited neutralizing antibody response in mice against infection by HIV-1 strains IIIB (clade B, X4), 92US657 (clade B, R5), and 94UG103 (clade A, X4R5). Anti-N46FdFc antibodies inhibited PIE7 binding to PFI, blocked gp41 six-helix bundle formation, and suppressed HIV-1 mediated cell-cell fusion. These findings provide an important clue for developing recombinant gp41 PFI mimetics-based HIV vaccines.

  16. The response of a neutral atom to a strong laser field probed by transient absorption near the ionisation threshold

    CERN Document Server

    Simpson, E R; Austin, D R; Diveki, Z; Hutchinson, S E E; Siegel, T; Ruberti, M; Averbukh, V; Miseikis, L; Strüber, C; Chipperfield, L; Marangos, J P

    2015-01-01

    We present transient absorption spectra of an extreme ultraviolet attosecond pulse train in helium dressed by an 800 nm laser field with intensity ranging from $2\\times10^{12}$ W/cm$^2$ to $2\\times10^{14}$ W/cm$^2$. The energy range probed spans 16-42 eV, straddling the first ionisation energy of helium (24.59 eV). By changing the relative polarisation of the dressing field with respect to the attosecond pulse train polarisation we observe a large change in the modulation of the absorption reflecting the vectorial response to the dressing field. With parallel polarized dressing and probing fields, we observe significant modulations with periods of one half and one quarter of the dressing field period. With perpendicularly polarized dressing and probing fields, the modulations of the harmonics above the ionisation threshold are significantly suppressed. A full-dimensionality solution of the single-atom time-dependent Schr\\"odinger equation obtained using the recently developed ab-initio time-dependent B-spline...

  17. Generation and characterization of antibodies against Asian elephant (Elephas maximus) IgG, IgM, and IgA.

    Science.gov (United States)

    Humphreys, Alan F; Tan, Jie; Peng, RongSheng; Benton, Susan M; Qin, Xiang; Worley, Kim C; Mikulski, Rose L; Chow, Dar-Chone; Palzkill, Timothy G; Ling, Paul D

    2015-01-01

    Asian elephant (Elephas maximus) immunity is poorly characterized and understood. This gap in knowledge is particularly concerning as Asian elephants are an endangered species threatened by a newly discovered herpesvirus known as elephant endotheliotropic herpesvirus (EEHV), which is the leading cause of death for captive Asian elephants born after 1980 in North America. While reliable diagnostic assays have been developed to detect EEHV DNA, serological assays to evaluate elephant anti-EEHV antibody responses are lacking and will be needed for surveillance and epidemiological studies and also for evaluating potential treatments or vaccines against lethal EEHV infection. Previous studies have shown that Asian elephants produce IgG in serum, but they failed to detect IgM and IgA, further hampering development of informative serological assays for this species. To begin to address this issue, we determined the constant region genomic sequence of Asian elephant IgM and obtained some limited protein sequence information for putative serum IgA. The information was used to generate or identify specific commercial antisera reactive against IgM and IgA isotypes. In addition, we generated a monoclonal antibody against Asian elephant IgG. These three reagents were used to demonstrate that all three immunoglobulin isotypes are found in Asian elephant serum and milk and to detect antibody responses following tetanus toxoid booster vaccination or antibodies against a putative EEHV structural protein. The results indicate that these new reagents will be useful for developing sensitive and specific assays to detect and characterize elephant antibody responses for any pathogen or vaccine, including EEHV.

  18. HbNIN2, a cytosolic alkaline/neutral-invertase, is responsible for sucrose catabolism in rubber-producing laticifers of Hevea brasiliensis (para rubber tree).

    Science.gov (United States)

    Liu, Shujin; Lan, Jixian; Zhou, Binhui; Qin, Yunxia; Zhou, Yihua; Xiao, Xiaohu; Yang, Jianghua; Gou, Jiqing; Qi, Jiyan; Huang, Yacheng; Tang, Chaorong

    2015-04-01

    In Hevea brasiliensis, an alkaline/neutral invertase (A/N-Inv) is responsible for sucrose catabolism in latex (essentially the cytoplasm of rubber-producing laticifers, the source of natural rubber) and implicated in rubber yield. However, neither the gene encoding this enzyme nor its molecular and biochemical properties have been well documented. Three Hevea A/N-Inv genes, namely HbNIN1, 2 and 3, were first cloned and characterized in planta and in Escherichia coli. Cellular localizations of HbNIN2 mRNA and protein were probed. From latex, active A/N-Inv proteins were purified, identified, and explored for enzymatic properties. HbNIN2 was identified as the major A/N-Inv gene functioning in latex based on its functionality in E. coli, its latex-predominant expression, the conspicuous localization of its mRNA and protein in the laticifers, and its expressional correlation with rubber yield. An active A/N-Inv protein was partially purified from latex, and determined as HbNIN2. The enhancement of HbNIN2 enzymatic activity by pyridoxal is peculiar to A/N-Invs in other plants. We conclude that HbNIN2, a cytosolic A/N-Inv, is responsible for sucrose catabolism in rubber laticifers. The results contribute to the studies of sucrose catabolism in plants as a whole and natural rubber synthesis in particular.

  19. A fast response hafnium selective polymeric membrane electrode based on N,N'-bis(alpha-methyl-salicylidene)-dipropylenetriamine as a neutral carrier.

    Science.gov (United States)

    Rezaei, B; Meghdadi, S; Zarandi, R Fazel

    2008-08-30

    In this study a new hafnium selective sensor was fabricated from polyvinylchloride (PVC) matrix membrane containing neutral carrier N,N'-bis(alpha-methyl-salicylidene)-dipropylenetriamine (Mesaldpt) as a new ionophore, sodium tetraphenyl borate (NaTPB) as anionic discriminator and dioctyl phthalate (DOP) as plasticizing solvent mediator in tetrahydrofuran solvent. The electrode exhibits Nernstian response for Hf(4+) (Hafnium(IV)) over a wide concentration range (2.0 x 10(-7) to 1.0 x 10(-1)M) with the determination coefficient of 0.9966 and slope of 15.1+/-0.1 mVdecades(-1). The limit of detection is 1.9 x 10(-7)M. The electrode has a fast response time of 18s and a working pH range of 4-8. The proposed membrane shows excellent discriminating ability towards Hf(4+) ion with regard to several alkali, alkaline earth transition and heavy metal ions. It can be used over a period of 1.5 months with good reproducibility. It is successfully applied for direct determination of Hf(4+) in solutions by standard addition method for real sample analysis.

  20. Radio Galaxies and the Magnetization of the IGM

    CERN Document Server

    Wiita, P J

    2003-01-01

    Observed radio galaxies had a much higher comoving density during the `quasar era', at z ~ 2-3, but these sources are only detectable for small fractions of their active lifetimes at such high z due to expansion losses and increased inverse Compton losses against the cosmic microwave background. Using recent models for the evolution of the size and luminosity of powerful double radio sources, as well as LCDM simulations of the cosmic web of baryonic material, we argue that during the quasar era a high volume fraction of this web was occupied by the lobes of double radio sources. They could have seeded the IGM with an average magnetic field approaching 10^{-8} G. Further, these advancing overpressured lobes could compress the denser interstellar gas clouds of the galaxies engulfed by them and thus trigger starbursts. This can probably account for much of the intense star-formation activity witnessed beyond z ~ 1.5. Also, the sweeping up of the ISM of the gas-rich galaxies by the rapidly advancing radio lobes m...

  1. Calorimetric features of IgM gammopathies. Implication for patient’s diagnosis and monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Krumova, Sashka; Todinova, Svetla; Danailova, Avgustina [Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 21, 1113 Sofia (Bulgaria); Petkova, Violeta; Dimitrova, Keranka; Gartcheva, Lidia [National Specialized Hospital for Active Treating of Haematological Diseases, Sofia 1756 (Bulgaria); Taneva, Stefka G., E-mail: stefka.germanova@ehu.es [Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 21, 1113 Sofia (Bulgaria); Unidad de Biofísica (CSIC-UPV/EHU) and Departamento de Bioquímica y Biología Molecular, Universidad del País Vasco, 48080 Bilbao (Spain)

    2015-09-10

    Highlights: • DSC reveals distinct calorimetric features for IgM gammopaties. • Calorimetry sets of IgM multiple myeloma and Waldenström’s macroglobulinemia patients. • DSC features correlate with the level of involved IgM heavy/light chains. • DSC and “Heavylite” are complementary methods for patients diagnostics/monitoring. - Abstract: The serum proteome of patients featuring immunoglobulin M (IgM) gammopathy and diagnosed as having IgM multiple myeloma or Waldenström’s macroglobulinemia was characterized by differential scanning calorimetry and HevyLite™ (HLC) assay. The thermodynamic properties of the thermograms and their deviation from the typical healthy thermogram were found to correlate with the monoclonal protein concentration and the level of the involved (monoclonal) IgM heavy/light chains. Patients monitoring during treatment showed that the variations in the shape of the DSC profiles corresponded to fluctuations of the IgM heavy/light chain levels verifying the two parameters as non-invasive markers for disease progression.

  2. IgM promotes the clearance of small particles and apoptotic microparticles by macrophages.

    Directory of Open Access Journals (Sweden)

    Michael L Litvack

    Full Text Available BACKGROUND: Antibodies are often involved in enhancing particle clearance by macrophages. Although the mechanisms of antibody-dependent phagocytosis have been studied for IgG in greater detail, very little is known about IgM-mediated clearance. It has been generally considered that IgM does not support phagocytosis. Recent studies indicate that natural IgM is important to clear microbes and other bioparticles, and that shape is critical to particle uptake by macrophages; however, the relevance of IgM and particle size in their clearance remains unclear. Here we show that IgM has a size-dependent effect on clearance. METHODOLOGY/PRINCIPAL FINDINGS: We used antibody-opsonized sheep red blood cells, different size beads and apoptotic cells to determine the effect of human and mouse IgM on phagocytosis by mouse alveolar macrophages. Our microscopy (light, epifluorescence, confocal and flow cytometry data show that IgM greatly enhances the clearance of small particles (about 1-2 micron by these macrophages. There is an inverse relationship between IgM-mediated clearance by macrophages and the particle size; however, macrophages bind and internalize many different size particles coated with IgG. We also show that IgM avidly binds to small size late apoptotic cells or bodies (2-5 micron and apoptotic microparticles (<2 µm released from dying cells. IgM also promotes the binding and uptake of microparticle-coated beads. CONCLUSIONS/SIGNIFICANCE: Therefore, while the shape of the particles is important for non-opsonized particle uptake, the particle size matters for antibody-mediated clearance by macrophages. IgM particularly promotes the clearance of small size particles. This finding may have wider implications in IgM-mediated clearing of antigens, microbial pathogens and dying cells by the host.

  3. Transcriptional heterogeneity of IgM+ cells in rainbow trout (Oncorhynchus mykiss) tissues.

    Science.gov (United States)

    Abós, Beatriz; Castro, Rosario; Pignatelli, Jaime; Luque, Alfonso; González, Lucia; Tafalla, Carolina

    2013-01-01

    TWO major classes of b lymphocytes have been described to date in rainbow trout: IgM(+) and IgT(+) cells. IgM(+) cells are mainly localized in the spleen, peripheral blood and kidney but are also found in other tissues. However, differences among IgM(+) cell populations attending to its location are poorly defined in fish. Thus, the aim of this work was to characterize the expression of different immune molecules such as chemokine receptors, Toll-like receptors (TLRs) and transcription factors on sorted IgM(+) lymphocytes from different rainbow trout tissues. IgM(+) populations from blood, spleen, kidney, gills, intestine and liver were isolated by cell sorting and the constitutive levels of transcription of these genes evaluated by real-time PCR. To further characterize B cells, we identified an MS4A sequence. In humans, the MS4A family includes several genes with immune functions, such as the B cell marker CD20 or FcRβ. Subsequently, we have also evaluated the mRNA levels of this MS4A gene in the different IgM(+) populations. The relevant differences in transcriptional patterns observed for each of these IgM(+) populations analyzed, point to the presence of functionally different tissue-specific B cell populations in rainbow trout. The data shown provides a pattern of genes transcribed in IgM(+) B cells not previously revealed in teleost fish. Furthermore, the constitutive expression of all the TLR genes analyzed in IgM(+) cells suggests an important role for these cells in innate immunity.

  4. Modeling the response of a fast ion loss detector using orbit tracing techniques in a neutral beam prompt-loss study on the DIII-D tokamak

    Energy Technology Data Exchange (ETDEWEB)

    Pace, D. C.; Heidbrink, W. W.; Muscatello, C. M.; Zhu, Y. B. [University of California-Irvine, Irvine, California 92697 (United States); Fisher, R. K.; Van Zeeland, M. A. [General Atomics, P.O. Box 85608, San Diego, California 92186-5608 (United States); Garcia-Munoz, M. [Max-Planck-Institut fuer Plasmaphysik, Garching D-85748 (Germany); Darrow, D. S.; Nazikian, R. [Princeton Plasma Physics Laboratory, Princeton, New Jersey 08543-0451 (United States)

    2010-10-15

    A numerical model describing the expected measurements of neutral beam prompt-losses by a newly commissioned fast ion loss detector (FILD) in DIII-D is presented. This model incorporates the well understood neutral beam deposition profiles from all eight DIII-D beamlines to construct a prompt-loss source distribution. The full range of detectable ion orbit phase space available to the FILD is used to calculate ion trajectories that overlap with neutral beam injection footprints. Weight functions are applied to account for the level of overlap between these detectable orbits and the spatial and velocity (pitch) properties of ionized beam neutrals. An experimental comparison is performed by firing each neutral beam individually in the presence of a ramping plasma current. Fast ion losses determined from the model are in agreement with measured losses.

  5. Motavizumab, A Neutralizing Anti-Respiratory Syncytial Virus (Rsv Monoclonal Antibody Significantly Modifies The Local And Systemic Cytokine Responses Induced By Rsv In The Mouse Model

    Directory of Open Access Journals (Sweden)

    Jafri Hasan S

    2007-10-01

    Full Text Available Abstract Motavizumab (MEDI-524 is a monoclonal antibody with enhanced neutralizing activity against RSV. In mice, motavizumab suppressed RSV replication which resulted in significant reduction of clinical parameters of disease severity. We evaluated the effect of motavizumab on the local and systemic immune response induced by RSV in the mouse model. Balb/c mice were intranasally inoculated with 106.5 PFU RSV A2 or medium. Motavizumab was given once intraperitoneally (1.25 mg/mouse as prophylaxis, 24 h before virus inoculation. Bronchoalveolar lavage (BAL and serum samples were obtained at days 1, 5 (acute and 28 (long-term post inoculation and analyzed with a multiplex assay (Beadlyte Upstate, NY for simultaneous quantitation of 18 cytokines: IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, KC (similar to human IL-8, IL-10, IL-12p40, IL-12p70, IL-13, IL-17, TNF-α, MCP-1, RANTES, IFN-γ and GM-CSF. Overall, cytokine concentrations were lower in serum than in BAL samples. By day 28, only KC was detected in BAL specimens at low concentrations in all groups. Administration of motavizumab significantly reduced (p

  6. Autoimmunity related to IgM monoclonal gammopathy of undetermined significance. Peripheral neuropathy and connective tissue sensibilization caused by IgM M-proteins

    DEFF Research Database (Denmark)

    Jønsson, V; Schrøder, H D; Nolsøe, C

    1988-01-01

    against structures in the endoneurium but no IgM autoimmunity in the direct fluorescence test. The latter improved clinically in parallel with a decrease in the M-protein indicating a pathogenetic role of the autoantibody. In three other cases, the IgM was bound to connective tissue structures, two......In eight of 10 consecutive cases of IgM monoclonal gammopathy of undetermined significance (MGUS), the M-protein had specificity towards various tissues as estimated by direct and indirect immunofluorescence studies of skin and/or sural nerve biopsies. Five of the cases had neuropathy. In three...... of them also had plasma antibodies against the peri- and endoneurium in the indirect fluorescence test. Finally, two cases showed no reaction of the M-protein against any tissue structures. Since an autoimmune pathogenesis is suspected, the HLA types of seven patients are reported....

  7. A novel recombinant Peste des petits ruminants-canine adenovirus vaccine elicits long-lasting neutralizing antibody response against PPR in goats.

    Directory of Open Access Journals (Sweden)

    Junling Qin

    Full Text Available BACKGROUND: Peste des petits ruminants (PPR is a highly contagious infectious disease of goats, sheep and small wild ruminant species with high morbidity and mortality rates. The Peste des petits ruminants virus (PPRV expresses a hemagglutinin (H glycoprotein on its outer envelope that is crucial for viral attachment to host cells and represents a key antigen for inducing the host immune response. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether H can be exploited to generate an effective PPRV vaccine, a replication-competent recombinant canine adenovirus type-2 (CAV-2 expressing the H gene of PPRV (China/Tibet strain was constructed by the in vitro ligation method. The H expression cassette, including the human cytomegalovirus (hCMV promoter/enhancer and the BGH early mRNA polyadenylation signal, was inserted into the SspI site of the E3 region, which is not essential for proliferation of CAV-2. Infectious recombinant rCAV-2-PPRV-H virus was generated in transfected MDCK cells and used to immunize goats. All vaccinated animals produced antibodies upon primary injection that were effective in neutralizing PPRV in vitro. Higher antibody titer was obtained following booster inoculation, and the antibody was detectable in goats for at least seven months. No serious recombinant virus-related adverse effect was observed in immunized animals and no adenovirus could be isolated from the urine or feces of vaccinated animals. Results showed that the recombinant virus was safe and could stimulate a long-lasting immune response in goats. CONCLUSIONS/SIGNIFICANCE: This strategy not only provides an effective PPR vaccine candidate for goats but may be a valuable mean by which to differentiate infected from vaccinated animals (the so-called DIVA approach.

  8. Comparative Accuracy of the InBios Scrub Typhus Detect IgM Rapid Test for the Detection of IgM Antibodies by Using Conventional Serology

    Science.gov (United States)

    Kingston, Hugh W. F.; Blacksell, Stuart D.; Tanganuchitcharnchai, Ampai; Laongnualpanich, Achara; Basnyat, Buddha; Day, Nicholas P. J.

    2015-01-01

    This study investigated the comparative accuracy of a recombinant 56-kDa type-specific antigen-based rapid diagnostic test (RDT) for scrub typhus for the detection of IgM antibodies by using conventional serology in well-characterized serum samples from undifferentiated febrile illness patients. The RDT showed high specificity and promising comparative accuracy, with 82% sensitivity and 98% specificity for samples defined positive at an IgM indirect immunofluorescence assay positivity cutoff titer of ≥1:1,600 versus 92% and 95% at ≥1:6,400, respectively. PMID:26291089

  9. Neutral Operator and Neutral Differential Equation

    Directory of Open Access Journals (Sweden)

    Jingli Ren

    2011-01-01

    Full Text Available In this paper, we discuss the properties of the neutral operator (Ax(t=x(t−cx(t−δ(t, and by applying coincidence degree theory and fixed point index theory, we obtain sufficient conditions for the existence, multiplicity, and nonexistence of (positive periodic solutions to two kinds of second-order differential equations with the prescribed neutral operator.

  10. Evaluation of Two Anti-Hepatitis E Virus IgM Kits

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To evaluate two commercial anti-hepatitis E virus (HEV) IgM kits used for differential diagnosis of acute enteric viral hepatitis. Methods The kit for IgM capture assay, was produced with a recombinant HEV structural protein protecting primates against experimental infection by different HEV genotypes, while the other kit for indirect ELISA was produced with recombinant structural proteins from different HEV genotypes. The serum specimens were taken from 241cases with a confirmed or presumptive diagnosis of hepatitis A and 74 cases with a confirmed or presumptive diagnosis of hepatitis E. Results The sensitivity and specificity of the IgM capture assay kit were 97% and 100%, respectively, and the corresponding values for the other kit were 70% and 78%, respectively. Conclusion The IgM capture assay kit has higher sensitivity and specificity in diagnosing acute enteric viral hepatitis E.

  11. Splenectomy associated changes in IgM memory B cells in an adult spleen registry cohort.

    Directory of Open Access Journals (Sweden)

    Paul U Cameron

    Full Text Available Asplenic patients have a lifelong risk of overwhelming post-splenectomy infection and have been reported to have low numbers of peripheral blood IgM memory B cells. The clinical value of quantitation of memory B cells as an indicator of splenic abnormality or risk of infection has been unclear. To assess changes in B cell sub-populations after splenectomy we studied patients recruited to a spleen registry (n = 591. A subset of 209 adult asplenic or hyposplenic subjects, and normal controls (n = 140 were tested for IgM memory B cells. We also determined a changes in IgM memory B cells with time after splenectomy using the cross-sectional data from patients on the registry and b the kinetics of changes in haematological markers associated with splenectomy(n = 45. Total B cells in splenectomy patients did not differ from controls, but memory B cells, IgM memory B cells and switched B cells were significantly (p<0.001 reduced. The reduction was similar for different indications for splenectomy. Changes of asplenia in routine blood films including presence of Howell-Jolly bodies (HJB, occurred early (median 25 days and splenectomy associated thrombocytosis and lymphocytosis peaked by 50 days. There was a more gradual decrease in IgM memory B cells reaching a stable level within 6 months after splenectomy. IgM memory B cells as proportion of B cells was the best discriminator between splenectomized patients and normal controls and at the optimal cut-off of 4.53, showed a true positive rate of 95% and false positive rate of 20%. In a survey of 152 registry patients stratified by IgM memory B cells around this cut-off there was no association with minor infections and no registry patients experienced OPSI during the study. Despite significant changes after splenectomy, conventional measures of IgM memory cells have limited clinical utility in this population.

  12. Serum HSV-1 and -2 IgM in pregnant women in Port Harcourt, Nigeria.

    Science.gov (United States)

    Okonko, I O; Cookey, T I; Okerentugba, P O; Frank-Peterside, N

    2015-01-01

    The present study was undertaken for the purpose of finding IgM antibodies against HSV-1 and 2 infections among pregnant women and also to evaluate correlation of Serum HSV-1 and 2 IgM in these pregnant women. A total of 180 pregnant women attending antenatal clinic at Braithwaite Memorial Specialist Hospital (BMSH) in Port Harcourt, Nigeria were consecutively recruited, after they had given consents to participate in the study. Serum of each sample was assayed for HSV-1&2 IgM antibody using a commercial ELISA. Five (2.8%) of the pregnant women were positive for IgM antibody against HSV-1&2. Marital status mainly correlated (χ(2) = 221.5, P HSV-2 infection and HSV-1/HSV-2 co-infection. Age, educational level, occupation, and gestation were not consistently associated (P>0.05) with HSV-1/HSV-2 infection and co-infection. We also observed a high overall anti-HSV-1&2 IgM seronegativity of 97.2% among these pregnant women. Group-specific seronegativity was also high ranging from 93.3-100%. Although the age-groups significantly differed, none of their variables showed statistical association with the seronegativity. This represents the first analysis of HSV IgM antibody reported in Port Harcourt, Nigeria and has important public health implications, particularly for pregnant women. Consideration of this information would benefit physicians providing primary gynecological and obstetric care to this population of women.

  13. Recombinant E2 glycoprotein of bovine viral diarrhea virus induces a solid humoral neutralizing immune response but fails to confer total protection in cattle

    Directory of Open Access Journals (Sweden)

    S. Chimeno Zoth

    2007-06-01

    Full Text Available Two recombinant baculoviruses were produced in order to obtain a bovine viral diarrhea virus (BVDV immunogen: AcNPV/E2 expressing E2 glycoprotein, and AcNPV/E0E1E2 expressing the polyprotein region coding for the three structural proteins of BVDV (E0, E1, and E2. Mice were immunized with Sf9 cells infected with the recombinant baculoviruses in a water in oil formulation and the production of neutralizing antibodies was evaluated. Since E2 elicited higher neutralizing antibody titers than E0-E1-E2 polyprotein, it was selected to immunize cattle. Calves received two doses of recombinant E2 vaccine and were challenged with homologous BVDV 37 days later. The recombinant immunogen induced neutralizing titers which showed a mean value of 1.5 ± 0.27 on the day of challenge and reached a top value of 3.36 ± 0.36, 47 days later (84 days post-vaccination. On the other hand, sera from animals which received mock-infected Sf9 cells did not show neutralizing activity until 25 days post-challenge (62 days post-vaccination, suggesting that these antibodies were produced as a consequence of BVDV challenge. Even when no total protection was observed in cattle, in vitro viral neutralization assays revealed that the recombinant immunogen was able to induce neutralizing antibody synthesis against the homologous strain as well as against heterologous strains in a very efficient way.

  14. Neutral Buoyancy Laboratory (NBL)

    Data.gov (United States)

    Federal Laboratory Consortium — The Neutral Buoyancy Laboratory (NBL) is an astronaut training facility and neutral buoyancy pool operated by NASA and located at the Sonny Carter Training Facility,...

  15. Complementary innate (anti-A-specific) IgM emerging from ontogenic O-GalNAc-transferase depletion: (Innate IgM complementarity residing in ancestral antigen completeness).

    Science.gov (United States)

    Arend, Peter

    2014-04-01

    The murine and the human genome have global properties in common. So the murine anti-A-specific complementary IgM and related human innate isoagglutinin represent developmental, 2-mercaptoethanol-sensitive, complement-binding glycoproteins, which do not arise from any measurable environmentally-induced or auto- immune response. The murine anti-A certainly originates from a cell surface- or cell adhesion molecule, which in the course of germ cell development becomes devoid of O-GalNAc-transferase and is released into the circulation. In human sera the enzyme occurs exclusively in those of blood group A- and AB subjects, while in group O(H) an identically encoded protein lets expect an opposite function and appears in conjunction with a complementary anti-A reactive glycoprotein. Since O-glycosylations rule the carbohydrate metabolism in growth and reproduction processes, we propose that the ancestral histo-(blood)-group A molecule arises in the course of O-GalNAc-glycosylations of glycolipids and protein envelops at progenitor cell surfaces. Germ cell development postulates embryonic stem cell fidelity, which is characterised by persistent production of α-linked O-GalNAc-glycans. They are determined by the A-allele within the human, "complete" histo (blood) group AB(O) structure that in early ontogeny is hypothesised to be synthesised independently from the final phenotype. The structure either passes "completely" through the germline, in transferase-secreting mature tissues becoming the "complete" phenotype AB, or disappears in exhaustive glycotransferase depletion from the differentiating cell surfaces and leaves behind the "incomplete" blood group O-phenotype, which has released a transferase- and O-glycan-depleted, complementary glycoprotein (IgM) into the circulation. The process implies, that in humans the different blood phenotypes evolve from a "complete" AB(O) molecular complex in a distinct enzymatic and/or complement cascade suggesting O

  16. Fat-associated lymphoid clusters control local IgM secretion during pleural infection and lung inflammation

    Science.gov (United States)

    Jackson-Jones, Lucy H.; Duncan, Sheelagh M.; Magalhaes, Marlène S.; Campbell, Sharon M.; Maizels, Rick M.; McSorley, Henry J.; Allen, Judith E.; Bénézech, Cécile

    2016-01-01

    Fat-associated lymphoid clusters (FALC) are inducible structures that support rapid innate-like B-cell immune responses in the serous cavities. Little is known about the physiological cues that activate FALCs in the pleural cavity and more generally the mechanisms controlling B-cell activation in FALCs. Here we show, using separate models of pleural nematode infection with Litomosoides sigmodontis and Altenaria alternata induced acute lung inflammation, that inflammation of the pleural cavity rapidly activates mediastinal and pericardial FALCs. IL-33 produced by FALC stroma is crucial for pleural B1-cell activation and local IgM secretion. However, B1 cells are not the direct target of IL-33, which instead requires IL-5 for activation. Moreover, lung inflammation leads to increased IL-5 production by type 2 cytokine-producing innate lymphoid cells (ILC2) in the FALC. These findings reveal a link between inflammation, IL-33 release by FALC stromal cells, ILC2 activation and pleural B-cell activation in FALCs, resulting in local and antigen-specific IgM production. PMID:27582256

  17. [Relevance of the new test Access Toxo IgM (II) in the serological interpretation of toxoplasmosis in pregnancy].

    Science.gov (United States)

    Flori, P; Hafid, J; Raberin, H; Patural, H; Varlet, M N; Tran Manh Sung, R

    2002-01-01

    The detection of specific IgM is an important element in the diagnosis of seroconversion. In this study, we compared the new test Access Toxo IgM (II) versus the previous test Access Toxo IgM (I). This comparative study was done with 507 random sera and 89 selected sera (seroconversion, residual IgM, non specific IgM). The sensitivity and the specificity are higher with the new test (100% & 100% versus 97% & 98,6% respectively). Then, the high sensitivity of Access Toxo IgM (II) is more convenient for the earlier diagnosis of primary Toxoplasma infection. Moreover, the Access Toxo IgM (II) test was evaluated with our first results in routine laboratory (11,000 serology results between June 2000 and June 2001). With these results, we can confirm the specificity of the new test, and also determine the relevance of anti-toxoplasmic IgM. Moreover, an increase of sensitivity leads to an increase of residual IgM detection: 64% (37/58) of positive IgM is residual (> 4 months) as compared to 35% (27/78) with the previous test. In these case, the initiation of other tests such as the avidity test is necessary to validate or invalidate a seroconversion during pregnancy.

  18. Neutralizing antibodies in hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)

    Mirjam B Zeisel; Samira Fafi-Kremer; Isabel Fofana; Heidi Barth; Fran(c)oise Stoll-Keller; Michel Doffo(e)l; Thomas F Baumert

    2007-01-01

    Hepatitis C virus (HCV) is a major cause of hepatitis world-wide. The majority of infected individuals develop chronic hepatitis which can then progress to liver cirrhosis and hepatocellular carcinoma. Spontaneous viral clearance occurs in about 20%-30% of acutely infected individuals and results in resolution of infection without sequaelae. Both viral and host factors appear to play an important role for resolution of acute infection. A large body of evidence suggests that a strong, multispecific and long-lasting cellular immune response appears to be important for control of viral infection in acute hepatitis C. Due too the lack of convenient neutralization assays,the impact of neutralizing responses for control of viral infection had been less defined. In recent years, the development of robust tissue culture model systems for HCV entry and infection has finally allowed study of antibody-mediated neutralization and to gain further insights into viral targets of host neutralizing responses.In addition, detailed analysis of antibody-mediated neutralization in individual patients as well as cohorts with well defined viral isolates has enabled the study of neutralizing responses in the course of HCV infection and characterization of the impact of neutralizing antibodies for control of viral infection. This review will summarize recent progress in the understanding of the molecular mechanisms of antibody-mediated neutralization and its impact for HCV pathogenesis.(C) 2007 The WJG Press. All rights reserved.

  19. Site-Specific N-Glycosylation of Recombinant Pentameric and Hexameric Human IgM

    Science.gov (United States)

    Moh, Edward S. X.; Lin, Chi-Hung; Thaysen-Andersen, Morten; Packer, Nicolle H.

    2016-07-01

    Glycosylation is known to play an important role in IgG antibody structure and function. Polymeric IgM, the largest known antibody in humans, displays five potential N-glycosylation sites on each heavy chain monomer. IgM can exist as a pentamer with a connecting singly N-glycosylated J-chain (with a total of 51 glycosylation sites) or as a hexamer (60 glycosylation sites). In this study, the N-glycosylation of recombinant pentameric and hexameric IgM produced by the same human cell type and culture conditions was site-specifically profiled by RP-LC-CID/ETD-MS/MS using HILIC-enriched tryptic and GluC glycopeptides. The occupancy of all putative N-glycosylation sites on the pentameric and hexameric IgM were able to be determined. Distinct glycosylation differences were observed between each of the five N-linked sites on the IgM heavy chains. While Asn171, Asn332, and Asn395 all had predominantly complex type glycans, differences in glycan branching and sialylation were observed between the sites. Asn563, a high mannose-rich glycosylation site that locates in the center of the IgM polymer, was only approximately 60% occupied in both the pentameric and hexameric IgM forms, with a difference in relative abundance of the glycan structures between the pentamer and hexamer. This study highlights the information obtained by characterization of the site-heterogeneity of a highly glycosylated protein of high molecular mass with quaternary structure, revealing differences that would not be seen by global glycan or deglycosylated peptide profiling.

  20. HIV-1自然感染中的中和抗体反应%Neutralizing antibodies responses during natural HIV-1 infection

    Institute of Scientific and Technical Information of China (English)

    任彩云; 李妍; 凌虹

    2012-01-01

    中和抗体(Nab)可以防止I型人类免疫缺陷病毒(HIV-1)侵入靶细胞.HIV-1感染数周后即可诱导产生Nab,这些早期抗体只能特异性地中和自体病毒但不能中和异源性病毒.在一些慢性感染者体内则可以检测到可同时中和同源性和异源性病毒的广谱中和抗体(BNab).BNab的靶点通常位于包膜蛋白的保守区域.HIV-1 BNab的产生还受到病毒变异及结构遮盖等因素的限制,同时Nab的中和广度与病毒载量具有相关性.%Neutralizing antibodies can protect a host against the infection by human immunodeficiency virus type 1 (HIV-1).Neutralizing antibodies can be induced several weeks after infection.However,the antibodies induced in the early stage can neutralize only the autologous but not heterologous viruses.Nevertheless,broad neutralizing antibodies,which can neutralize both autologous and heterologous viruses,have been found in some chronic patients.Inaddition,broad neutralizing antibodies usually target the conserved regions of HIV-1 envelope glycoprotein.However,the envelope glycoprotein mutation and its structure shielding limit the induction of these antibodies.

  1. Anti-PEG IgM Is a Major Contributor to the Accelerated Blood Clearance of Polyethylene Glycol-Conjugated Protein.

    Science.gov (United States)

    Mima, Yu; Hashimoto, Yosuke; Shimizu, Taro; Kiwada, Hiroshi; Ishida, Tatsuhiro

    2015-07-06

    Limited therapeutic efficacy of polyethylene glycol-conjugated (PEGylated) protein drugs has been recently reported in animals and human following repeat injections. Since there are reports that an accelerated blood clearance (ABC) phenomenon is caused by repeated injection of PEGylated liposome, there is an assumption that PEGylated proteins lose their long circulating property when they are injected repeatedly due to the induction of anti-PEG antibody. Although induction of anti-PEG antibody by PEGylated protein has been reported, there is little evidence of accelerated blood clearance of PEGylated protein upon repeated injection. Herein, we investigated the blood concentration of PEGylated ovalbumin (PEG-OVA), a model PEGylated protein, upon its repeated injection. A single intravenous administration of PEG-OVA elicited an anti-PEG IgM response but not anti-PEG IgG response, while the administration did not elicit antibody against OVA. At 24 h postinjection of test PEG-OVA, although control mice showed 41.6% dose of PEG-OVA in blood, the mice pretreated with PEG-OVA showed rapid clearance of test PEG-OVA from blood and undetectable level of PEG-OVA. Interestingly, the anti-PEG IgM induced by PEGylated liposome did not affect the blood concentration of subsequent dose of PEG-OVA. Our result suggests that anti-PEG IgM is a major contributor to the accelerated blood clearance of PEG-conjugated protein, but the presence of anti-PEG IgM in blood circulation does not necessarily affect circulating property of entire PEGylated materials.

  2. Simultaneous Quantification of Anticardiolipin IgG and IgM by Time Resolved Fluoroimmunoassay

    Science.gov (United States)

    Liu, Jie; Li, Mei; Ye, Yan; Chen, Yu

    2016-01-01

    The autoimmune disease antiphospholipid syndrome (APS) is characterized by the presence of anticardiolipin antibodies (aCL), along with anti-β2-glycoprotein I (β2GPI) antibodies and lupus anticoagulant (LA). In this study, we developed a time-resolved fluoroimmunoassay (TRFIA) system for simultaneous quantification of aCL IgG and IgM. A 96-well microtiter plate precoated with the complex of cardiolipin from bovine heart and bovine β2GPI was incubated with the anticardiolipin IgG and IgM standard substance or serum, and the conjugate of Eu3+-labeled anti-human IgG and Sm3+-labeled anti-human IgM was pipetted to the wells to form a tipical double-antibody-sandwich immunoreactions; finally the fluorescent intensity of Eu3+ and Sm3+ was detected to reflect the quantity of anticardiolipin IgG and IgM. This assay showed a good relationship between fluorescence intensities and the concentration of anticardiolipin antibody(aCL) IgG and IgM, with a low-end sensitivity of 0.1 U/ml for IgG and 0.1 U/ml for IgM, respectively. The intra- and inter-assay coefficients of variation (CV) of the calibrators was 3.0% and 4.51% for IgG, and 2.76% and 4.45% for IgM. The average recovery was 100.38% for aCL IgG and 100.45% for aCL IgM. For serum samples, the results of our method showed a good correlation with those obtained with ELISA kit. Simultaneous detection of aCL-IgG and aCL-IgM in the same reaction well can optimize assay performance by avoiding potential influence of different reaction conditions-timing, and well-to-well difference in concentration and characteristics of cardiolipin antigen. The results of a combo aCL-IgG and aCL-IgM assay for the same sample are more consistent and more reliable. This dual-label time-resolved fluoroimmunoassay is sensitive for detecting aCL IgG and IgM across a wide concentration range with stable reagents and may assist in the clinical diagnosis of antiphospholipid syndrome. PMID:27661084

  3. Profiles of acute cytokine and antibody responses in patients infected with avian influenza A H7N9.

    Directory of Open Access Journals (Sweden)

    Rui Huang

    Full Text Available The influenza A H7N9 virus outbreak in Eastern China in the spring of 2013 represented a novel, emerging avian influenza transmission to humans. While clinical and microbiological features of H7N9 infection have been reported in the literature, the current study investigated acute cytokine and antibody responses in acute H7N9 infection. Between March 27, 2013 and April 23, 2013, six patients with confirmed H7N9 influenza infection were admitted to Drum Tower Hospital, Nanjing, China. Acute phase serum cytokine profiles were determined using a high-throughput multiplex assay. Daily H7 hemagglutinin (HA-specific IgG, IgM, and IgA responses were monitored by ELISA. Neutralizing antibodies specific for H7N9 viruses were determined against a pseudotyped virus expressing the novel H7 subtype HA antigen. Five cytokines (IL-6, IP-10, IL-10, IFNγ, and TNFα were significantly elevated in H7N9-infected patients when compared to healthy volunteers. Serum H7 HA-specific IgG, as well as IgM and IgA responses, were detected within 8 days of disease onset and increased in a similar pattern during acute infection. Neutralizing antibodies developed shortly after the appearance of binding antibody responses and showed similar kinetics as a fraction of the total H7 HA-specific IgG responses. H7N9 infection resulted in hallmark serum cytokine increases, which correlated with fever and disease persistence. The novel finding of simultaneous development of IgG, IgM, and IgA responses in acute H7N9 infection points to the potential for live influenza viruses to elicit fast and potent protective antibodies to limit the infection.

  4. IgM nephropathy: is it closer to minimal change disease or to focal segmental glomerulosclerosis?

    Science.gov (United States)

    Brugnano, R; Del Sordo, R; Covarelli, C; Gnappi, E; Pasquali, S

    2016-08-01

    Immunoglobulin (Ig)M nephropathy (IgMN), known since 1978, is a very controversial clinicopathological entity characterized by IgM diffuse deposits in the mesangium at immunofluorescence whereas light microscop identifies minimal glomerular lesion, hypercellularity and expansion of the mesangium or sclerotic focal, segmental lesion. Clinically, it is a nephrotic syndrome, especially in pediatric patients, or asymptomatic proteinuria and/or isolated hematuria. These characteristics narrowly define IgMN between minimal change disease and focal segmental glomerulosclerosis, so it is not often recognized as a separate pathology. Homogeneous epidemiologic, pathogenetic, clinical or histological data are not available. Recent research on the pathogenetic role of mesangial IgM has, however, renewed interest in IgMN and naturally the controversies.

  5. Symptomatic Secondary Selective IgM Immunodeficiency in Adult Man with Undiagnosed Celiac Disease

    Directory of Open Access Journals (Sweden)

    Eli Magen

    2012-01-01

    Full Text Available Selective IgM immunodeficiency (SIgMID is a heterogeneous disorder with no known genetic background and may occur as a primary or a secondary condition. Celiac disease has been reported in association with several humeral immunodeficiencies, including isolated severe selective IgA deficiency, panhypogammaglobulinemia, and isolated combined IgA and IgM deficiency. There are only few reported cases of pediatric and adult patients with SIgMID and celiac disease. In this paper, we describe an adult patient with a symptomatic secondary SIgMID associated with undiagnosed celiac disease, with a resolution of clinical symptoms of immunodeficiency and serum IgM normalization following a gluten-free diet.

  6. Poroid Fungi of Hungary in the Collection of Zoltán Igmándy

    Directory of Open Access Journals (Sweden)

    SZABÓ, Ilona

    2012-01-01

    Full Text Available Zoltán Igmándy (1925–2000, prominent Hungarian mycologist, worked as professor of forest protection at the University of West-Hungary Sopron. His main research area was the investigation of wood-inhabiting poroid fungi of Hungary, their occurrence and importance in forest pathology and wood protection. During his 40 years of scientific activity Igmándy created a rich fungal collection (herbarium Z. Igmándy which includes the complete polypore mycota known to occur in Hungary until 1990. The paper provides a brief compendium of the collection, a list of species characterised by the number of specimens, number of sampling locations and enumeration of the hosts and substrata of the specimens.

  7. Capture ELISA for IgM antibodies against Plasmodium falciparum glutamate rich protein

    DEFF Research Database (Denmark)

    Dziegiel, Morten Hanefeld; Borre, M B; Petersen, E

    1992-01-01

    This report describes a novel mu chain capture ELISA for the detection of IgM antibodies against a Plasmodium falciparum antigen. A fragment of the 220 kDa P. falciparum glutamate rich protein containing amino acid residues 489-1271 was expressed in E. coli as a recombinant chimeric beta-galactos......This report describes a novel mu chain capture ELISA for the detection of IgM antibodies against a Plasmodium falciparum antigen. A fragment of the 220 kDa P. falciparum glutamate rich protein containing amino acid residues 489-1271 was expressed in E. coli as a recombinant chimeric beta...

  8. Persistence of the protective immunity and kinetics of the isotype specific antibody response against the viral nucleocapsid protein after experimental Schmallenberg virus infection of sheep.

    Science.gov (United States)

    Poskin, Antoine; Verite, Stephanie; Comtet, Loic; Van der Stede, Yves; Cay, Brigitte; De Regge, Nick

    2015-10-15

    Schmallenberg virus (SBV) is an Orthobunyavirus that induces abortion, stillbirths and congenital malformations in ruminants. SBV infection induces a long lasting seroconversion under natural conditions. The persistence of the protective immunity and the isotype specific antibody response upon SBV infection of sheep has however not been studied in detail. Five sheep were kept in BSL3 facilities for more than 16 months and subjected to repeated SBV infections. Blood was regularly sampled and organs were collected at euthanasia. The presence of SBV RNA in serum and organs was measured with quantitative real-time PCR. The appearance and persistence of neutralizing and SBV nucleoprotein (N) isotype specific antibodies was determined with virus neutralization tests (VNT) and ELISAs. The primo SBV infection protected ewes against clinical signs, viraemia and virus replication in organs upon challenge infections more than 15 months later. Production of neutralizing SBV specific antibodies was first detected around 6 days post primo-inoculation with VNT and correlated with the appearance of SBV-N specific IgM antibodies. These IgM antibodies remained present for 2 weeks. SBV-N specific IgG antibodies were first detected between 10 and 21 dpi and reached a plateau at 28 dpi. This plateau remained consistently high and no significant decrease in titre was found over a period of more than 1 year. Similar results were found for the neutralising antibody response. In conclusion, the SBV specific IgM response probably eliminates SBV from the blood and the protective immunity induced by SBV infection protects sheep against reinfection for at least 16 months.

  9. Broadly neutralizing antibodies targeted to mucin-type carbohydrate epitopes of human immunodeficiency virus

    DEFF Research Database (Denmark)

    Hansen, J E; Nielsen, C; Arendrup, M

    1991-01-01

    The cancer-related mucin-type carbohydrate neoantigen Tn was found on gp160 and gp120 of human immunodeficiency virus (HIV). Immunoglobulin G (IgG) and IgM monoclonal antibodies (MAbs) against Tn neutralized infection with cell-free virus and blocked fusion between HIV-infected and uninfected cells......; this binding was inhibitable by pure Tn antigen, and indications were found that this inhibition occurred at a pre-entry step. Boosting the naturally occurring low-titer anti-Tn activity may be of prophylactic value, as suggested by the in vitro neutralization found in this study....

  10. PDGF is required for remyelination-promoting IgM stimulation of oligodendrocyte progenitor cell proliferation.

    Directory of Open Access Journals (Sweden)

    Jens O Watzlawik

    Full Text Available BACKGROUND: Promotion of remyelination is a major goal in treating demyelinating diseases such as multiple sclerosis (MS. The recombinant human monoclonal IgM, rHIgM22, targets myelin and oligodendrocytes (OLs and promotes remyelination in animal models of MS. It is unclear whether rHIgM22-mediated stimulation of lesion repair is due to promotion of oligodendrocyte progenitor cell (OPC proliferation and survival, OPC differentiation into myelinating OLs or protection of mature OLs. It is also unknown whether astrocytes or microglia play a functional role in IgM-mediated lesion repair. METHODS: We assessed the effect of rHIgM22 on cell proliferation in mixed CNS glial and OPC cultures by tritiated-thymidine uptake and by double-label immunocytochemistry using the proliferation marker, Ki-67. Antibody-mediated signaling events, OPC differentiation and OPC survival were investigated and quantified by Western blots. RESULTS: rHIgM22 stimulates OPC proliferation in mixed glial cultures but not in purified OPCs. There is no proliferative response in astrocytes or microglia. rHIgM22 activates PDGFαR in OPCs in mixed glial cultures. Blocking PDGFR-kinase inhibits rHIgM22-mediated OPC proliferation in mixed glia. We confirm in isolated OPCs that rHIgM22-mediated anti-apoptotic signaling and inhibition of OPC differentiation requires PDGF and FGF-2. We observed no IgM-mediated effect in mature OLs in the absence of PDGF and FGF-2. CONCLUSION: Stimulation of OPC proliferation by rHIgM22 depends on co-stimulatory astrocytic and/or microglial factors. We demonstrate that rHIgM22-mediated activation of PDGFαR is required for stimulation of OPC proliferation. We propose that rHIgM22 lowers the PDGF threshold required for OPC proliferation and protection, which can result in remyelination of CNS lesions.

  11. Neutralization of English Consonants

    Institute of Scientific and Technical Information of China (English)

    庞彬彬

    2011-01-01

    This paper gives a brief account of English consonant cluster's structure and phonetic features from the perspective of the definition and cause of neutralization of English consonants as well as their distinctive features and oppositions.It comes up with the final conclusion that neutralization exists in only thirteen English consonant clusters,among a large number of consonant clusters.

  12. Comparison of two chemiluminescent immunoassays in the detection of measles IgM antibodies.

    Science.gov (United States)

    Gómez-Camarasa, Cristina; Lara-Oya, Ana; Cobo, Fernando; Sampedro-Martínez, Antonio; Rodríguez-Granger, Javier; Gutierrez-Fernández, José; Navarro-Marí, José María

    2016-11-01

    Serological confirmation of measles is achieved by detecting the specific immunoglobulin M (IgM), and it is important to evaluate new commercial inmunoassays in order to ensure the quality of results. The objective of this study was to compare the performance of a novel automated chemiluminescent immunoassay (CLIA), Virclia IgM measles (Vircell, Spain), with that of the widely used Liaison measles IgM assay (DiaSorin, Italy). A panel of 86 sera from laboratory-confirmed cases was used for the sensitivity calculation, and 59 sera from healthy individuals and those with other viral infections were used for the specificity calculation. Sensitivity values were 96.5% for Virclia and 97.6% for Liaison; specificity values were 93.2% for Virclia and 96.6% for Liaison; neither difference was statistically significant VirClia IgM measles is a good alternative to other immunoassays for the serological confirmation of measles. Copyright © 2016. Published by Elsevier B.V.

  13. Typhidot (IgM as a reliable and rapid diagnostic test for typhoid fever

    Directory of Open Access Journals (Sweden)

    Sushma Krishna

    2011-01-01

    Full Text Available Introduction: Typhoid fever still continues to be a major public health problem, particularly in developing countries. A simple, reliable, affordable, and rapid diagnostic test has been a long-felt need of the clinicians. We, therefore, prospectively evaluated the sensitivity and specificity of Typhidot (IgM, a serological test to identify IgM antibodies against Salmonella typhi. Materials and Methods: The study was carried out in the Department of Microbiology, Apollo Hospital, Bangalore between January 2009 and March 2009 on a total of 186 samples from clinically suspected febrile patients. Blood culture as well as Typhidot test was performed for each of the cases. Results: Out of 61 clinically diagnosed typhoid fever, 50 were blood culture positive for S. typhi all 50 were Typhidot (IgM positive and 11 were missed out on both. The sensitivity, specificity, positive and negative predictive values of the test using blood culture as gold standard were 100%, 95.5%, 89.2%, and 100%, respectively for typhoid fever. Conclusion: Typhidot (IgM test is rapid, easy to perform, and reliable for diagnosing typhoid fever, and useful for small, less equipped laboratories as well as for the laboratories with better facilities in typhoid endemic countries.

  14. Atypical IgM multiple myeloma with deletion of c-MAF.

    Science.gov (United States)

    Juárez Salcedo, L M; López Rubio, M; Gil Fernández, J J; Garcia-Suarez, J; Magro, E; Arranz, E; Gutiérrez Jomarrón, I; Marcellini Antonio, S; Blasco, A; Burgaleta, C

    2015-10-01

    IgM multiple myeloma (MM) is a rare subtype of myeloma that shares clinical and pathological features with Waldenström's macroglobulinaemia. These are two separate entities that differ both in therapy and prognosis. We report a 57-year-old male, who presented with anaemia, hypercalcaemia, acute renal failure and several vertebral fractures that clinically suggested a multiple myeloma. Further investigations revealed a serum monoclonal component of IgM lambda type and a bone marrow infiltrated by small, lymphoplasmocytic cells. IgM MM was finally diagnosed by means of both inmunophenotypic and immunohistochemistry techniques, stressing the importance of inmunophenotypic evaluation when clinical and morphological features are discordant. Fluorescence in situ hybridization (FISH) studies disclosed a particular combination of deletion 13q14, t(11;14) and monoallelic deletion C-MAF without t(14;16). The clinical evolution after a Bortezomib-containing polychemotherapy and autologous stem cell transplantation (ASCT) conditioned with busulphan and melphalan is also presented. This very uncommon case highlights the impact of immunophenotyping on the differential diagnosis between IgM MM and WM, to choose the best treatment and establish an appropriate outcome. © 2015 John Wiley & Sons Ltd.

  15. Dark Matter annihilation energy output and its effects on the high-z IGM

    CERN Document Server

    Araya, Ignacio J

    2013-01-01

    We study the case of DM self annihilation, in order to asses its importance as an energy injection mechanism, to the IGM in general, and to the medium within particular DM haloes. We consider two well motivated WIMP candidates, the SUSY neutralino and the first KK excited state of the B electroweak boson. We explicitly compute the energy output (or luminosity) of DM haloes due to annihilations, and compare the obtained luminosities with the standard AGN feedback process, concluding that DM annihilation does not provide the necessary output as to constitute an important feedback mechanism. We then compute the energy injection rate per baryon of annihilations on the IGM, in order to calculate the effects that it has on its temperature and ionization fraction. We find significant deviations in the evolutions of the temperature and ionization fraction of the IGM, in scenarios that take into account the clustering of DM at all levels, such that a 1TeV WIMP may, for example, maintain the temperature of the IGM on t...

  16. Accuracy of a Commercial IgM ELISA for the Diagnosis of Human Leptospirosis in Thailand

    Science.gov (United States)

    Desakorn, Varunee; Wuthiekanun, Vanaporn; Thanachartwet, Vipa; Sahassananda, Duangjai; Chierakul, Wirongrong; Apiwattanaporn, Apichat; Day, Nicholas P.; Limmathurotsakul, Direk; Peacock, Sharon J.

    2012-01-01

    The Leptospira immunoglobulin M enzyme-linked immunosorbent assay (IgM ELISA) has been recommended for the rapid diagnosis of leptospirosis in endemic areas. We conducted a retrospective case-control study of 218 patients (109 leptospirosis cases confirmed by Leptospira culture and/or microscopic agglutination test and 109 control patients with acute febrile illness) to evaluate the diagnostic accuracy of a commercial IgM ELISA (Panbio) in northeast Thailand. Paired serum samples taken on admission and at least 10 days after the onset of symptoms were tested. Using the cutoff value recommended by the manufacturer (11 Panbio units), sensitivity and specificity of IgM ELISA on paired sera were 90.8% and 55.1%. A receiver operating characteristic curve was used to determine the optimal cutoff value. This was 20 Panbio units, which gave a sensitivity and specificity of 76.1% and 82.6%, respectively, on paired sera. We conclude that using either cutoff value, the accuracy of IgM ELISA is limited in our setting. PMID:22403329

  17. An M-antibody capture radioimmunoassay (MACRIA) for detection of JC virus-specific IgM.

    Science.gov (United States)

    Knowles, W A; Gibson, P E; Hand, J F; Brown, D W

    1992-10-01

    A solid-phase M-antibody capture radioimmunoassay (MACRIA) for detecting JC-specific IgM is described. The assay is based on a JC-specific monoclonal antibody (17.7.6) and Nonidet P40-treated, glycine-extracted antigen. MACRIA is more sensitive for JC IgM detection than haemagglutination inhibition (HI) following serum fractionation on a sucrose density gradient, and can be applied to large numbers of sera. The specificity of the assay was confirmed by examining sera from several acute virus infections and also those containing rheumatoid factor. Sera collected from renal transplant recipients with known active JC virus infection were found to contain more than 5 units of JC IgM. In this group of patients JC IgM represents either primary or reactivated JC infection. JC IgM was detected by MACRIA in 15 of 100 unselected blood donors, indicating that JC IgM is frequently produced in healthy seropositive individuals. Thirteen of the 15 sera positive from blood donors contained only low levels of JC IgM (< 5 units), but the specificity of all these results was confirmed in a blocking assay. It is suggested that these low levels of JC IgM may occur in up to 28% of seropositive individuals and result from active JC antigenic stimulation in healthy immunocompetent adults.

  18. Morphology, luminescence, and electrical resistance response to H 2 and CO gas exposure of porous InP membranes prepared by electrochemistry in a neutral electrolyte

    Science.gov (United States)

    Volciuc, O.; Monaico, E.; Enachi, M.; Ursaki, V. V.; Pavlidis, D.; Popa, V.; Tiginyanu, I. M.

    2010-11-01

    Porous InP membranes have been prepared by anodization of InP wafers with electron concentration of 1 × 10 17 cm -3 and 1 × 10 18 cm -3 in a neutral NaCl electrolyte. The internal surfaces of pores in some membranes were modified by electrochemical deposition of gold in a pulsed voltage regime. Photoluminescence and photosensitivity measurements indicate efficient light trapping and porous surface passivation. The photoluminescence and electrical resistivity of the membranes are sensitive to the adsorption of H 2 and CO gas molecules. These properties are also influenced by the deposition of Au nanoparticles inside the pores.

  19. Morphology, luminescence, and electrical resistance response to H{sub 2} and CO gas exposure of porous InP membranes prepared by electrochemistry in a neutral electrolyte

    Energy Technology Data Exchange (ETDEWEB)

    Volciuc, O.; Monaico, E.; Enachi, M. [National Center for Materials Study and Testing, Technical University of Moldova, Bd. Stefan cel Mare 168, Chisinau 2004 (Moldova, Republic of); Ursaki, V.V., E-mail: ursaki@yahoo.com [Institute of Applied Physics, Academy of Sciences of Moldova, Academy str. 5, Chisinau 2028 (Moldova, Republic of); Pavlidis, D. [Fachgebiet fuer Hoechstfrequenzelektronik, Technische Universitaet Darmstadt, Merckstrasse 25, Darmstadt 64283 (Germany); Popa, V. [National Center for Materials Study and Testing, Technical University of Moldova, Bd. Stefan cel Mare 168, Chisinau 2004 (Moldova, Republic of); Fachgebiet fuer Hoechstfrequenzelektronik, Technische Universitaet Darmstadt, Merckstrasse 25, Darmstadt 64283 (Germany); Tiginyanu, I.M. [National Center for Materials Study and Testing, Technical University of Moldova, Bd. Stefan cel Mare 168, Chisinau 2004 (Moldova, Republic of); Institute of Electronic Engineering and Nanotechnologies, Academy of Sciences of Moldova, Academy str. 3/3, Chisinau 2028 (Moldova, Republic of)

    2010-11-15

    Porous InP membranes have been prepared by anodization of InP wafers with electron concentration of 1 x 10{sup 17} cm{sup -3} and 1 x 10{sup 18} cm{sup -3} in a neutral NaCl electrolyte. The internal surfaces of pores in some membranes were modified by electrochemical deposition of gold in a pulsed voltage regime. Photoluminescence and photosensitivity measurements indicate efficient light trapping and porous surface passivation. The photoluminescence and electrical resistivity of the membranes are sensitive to the adsorption of H{sub 2} and CO gas molecules. These properties are also influenced by the deposition of Au nanoparticles inside the pores.

  20. "Unconventional" Neutralizing Activity of Antibodies Against HIV

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Neutralizing antibodies are recognized to be one of the essential elements of the adaptive immune response that must be induced by an effective vaccine against HIV. However, only a limited number of antibodies have been identified to neutralize a broad range of primary isolates of HIV-1 and attempts to induce such antibodies by immunization were unsuccessful. The difficulties to generate such antibodies are mainly due to intrinsic properties of HIV-1 envelope spikes, such as high sequence diversity, heavy glycosylation, and inducible and transient nature of certain epitopes. In vitro neutralizing antibodies are identified using "conventional" neutralization assay which uses phytohemagglutinin (PHA)-stimulated human PBMCs as target cells. Thus, in essence the assay evaluates HIV-1 replication in CD4+ T cells. Recently, several laboratories including us demonstrated that some monoclonal antibodies and HIV-1-specific polyclonal IgG purified from patient sera, although they do not have neutralizing activity when tested by the "conventional" neutralization assay, do exhibit potent and broad neutralizing activity in "unconventional" ways. The neutralizing activity of these antibodies and IgG fractions is acquired through post-translational modifications, through opsonization of virus particles into macrophages and immature dendritic cells (iDCs), or through expression of antibodies on the surface of HIV-1-susceptible cells. This review will focus on recent findings of this area and point out their potential applications in the development of preventive strategies against HIV.

  1. Determination of Antibodies (IgG, IgM against Toxoplasma gondii in Patients with Cancer

    Directory of Open Access Journals (Sweden)

    M Pedram

    2007-08-01

    Full Text Available Background: The aim of this study was determination of antibodies (IgG, IgM against Toxoplasma in malignant patients in order to refer the patients on time to the physician for treatment.Methods: This study was carried out on 252 malignant patients and 252 healthy normal subjects (as control obtained from Shafa Hospital and Medical Diagnostic Laboratory (Iran-Zamin, in Ahwaz city. Patient's information was recorded in a questionnaire before sampling. Serum samples of patients were examined for IgG and IgM antibodies by ELISA technique using Trinity kits. Results: The results of this study revealed the presence of Toxoplasma antibodies in 114 (45.2% cases of patients who were positive for Toxoplasma IgG antibodies, and 26 (10.3% cases were confirmed to be positive for Toxoplasma IgM antibodies and also 17 (6.7% of cases had both IgG and IgM antibodies against Toxoplasma gondii. In control group 92 (36.5% cases and 15 (6% cases revealed seropositive for IgG and IgM antibodies, respectively. There were no significant differences between sex, close contact with cat, living region, chemotherapy, and seropositivity rate of toxoplasmosis in patients. Comparing the age groups, the highest seropositive rate showed in the age of 51 years or higher, and their rates had tendency to increase with age in both groups. No seropositivity significant relationship was found between patients and control group.Conclusion: According to the prevalence of positive cases in these patients, it is necessary to examine the patients for toxoplasmosis before, during and after chemotherapy.

  2. Study of Erythropoeitin on IGM serum levels in HCV positive patients on regular HD

    Directory of Open Access Journals (Sweden)

    Khaled Abo Seif , Mona Hosny And Ahmed Aboud

    2012-01-01

    Full Text Available Both uremia and HD process cause immunosuppression in HD patients. There was significant increase of total serum IgG and IgM levels found in patients with chronic HCV compared with healthy controls. There is evidence pointing to direct effect of rHuEPO upon B cells. High doses of recombinant human erythropoietin (rHu EPO enhanced in vitro Ig production and proliferation of various plasma cell lines, as well as human plasma cells generated in vitro. Study was conducted at hemodialysis Unit of Shubra Municipal hospital between August 2010 to February 2011. 30 HCV positive patients on regular hemodialysis were included in study, using bicarbonate dialysate and polysulfone membrane dialyser, for 4 hours 3 times weekly. Patients were divided into 2 groups: first group: 15 patients on EPO therapy. 4000 IU/week and second group not taking EPO for all patients full clinical examination was done, CBC, BUN, serum creatinine, ALT, AST, serum albumin and serum IgM by ELISA (quantitative assay, were done. There was no significant difference between 2 groups as regards age, sex distribution, WBC count, ALT, AST, serum creatinine, BUN and IgM serum level. First group had borderline significant higher Hgb and Hct than second group (p = 0.056. Females didn't have higher serum IgM level than males (p = 0.403. All correlations of IgM serum level to other parameters of study were irrelevant. Uremia seems to protect ESRD patients on regular HD from complications of HCV and also EPO effect on Ig serum levels.

  3. 响应面法优化高粱米淀粉的中性蛋白酶法提取工艺%Optimization of sorghum starch extracting technology with neutral protease hydrolysis by response surface methodology

    Institute of Scientific and Technical Information of China (English)

    杜洋; 史岩; 陈海华

    2015-01-01

    以高粱米为原料,以淀粉回收率为指标,通过单因素及响应面优化试验,对高粱米淀粉的中性蛋白酶法提取工艺进行了优化。结果表明,中性蛋白酶法提取高粱米淀粉的最佳工艺条件为,中性蛋白酶添加量600 U/g,酶处理温度35℃,酶处理pH 7.0,酶处理时间3.2 h,粉碎粒径132μm。在此条件下,高粱米淀粉回收率为83.35%,与普通水提法相比增加了16.49%,具有较高的应用价值。%According to the sorghum starch yield,theoptimum sorghum starch extraction technology with neutral protease hydrolysis from sorghum seeds was investigated by single factor experiments and response surface methodology. The result showed that theoptimum extractionconditions were as follows,the neutral proteaseof 600 U/g,the hydrolysis temperatureof 35℃,the hydrolysis pHof 7.0,the hydrolysis timeof 3.2 h,particle sizeof 132μm. Under theconditions,the sorghum starch yield was 83.35%. Compared with extraction with water,the sorghum starch yield with neutral protease hydrolysis was raised by 16.49%. Therefore,sorghum starch extraction with neutral protease hydrolysis was more practical.

  4. IL-6 mediated isotype specific suppression of hapten specific IgE in serum of BPO-KLH sensitized mice: role of IFN alpha in maintainance of hapten specific IgE responses.

    Science.gov (United States)

    Auci, D L; Miller, H; Chice, S M; Durkin, H G

    1994-04-01

    The ability of IL-6 or IFN alpha or antibodies to these cytokines to regulate serum levels of hapten specific immunoglobulins (IgM, IgG1, IgE, IgA) was studied in BPO-KLH (benzylpenicilloyl-keyhole limpet hemocyanin) sensitized BALB/c mice at the peak of a hapten specific IgE antibody forming cell (AFC) response. To induce peak IgE responses, mice were injected intraperitonealy (i.p.) with BPO-KLH (10 micrograms) in aluminum hydroxide gel (alum) on days 0, 21, and 42. On day 44, mice were injected s.c. with IL-6 (100-1000 U), IFN alpha (1000-10,000 U), anti-IL-6 (100-1000 neutralizing units [NU]), or anti-IFN alpha (1000-10,000 NU). On day 46, levels of BPO specific IgM, IgG1, IgE and IgA in serum were determined (ELISA). Data are expressed as micrograms/ml. IL-6 suppressed BPO specific IgE in serum in isotype specific fashion (to > 90%), increasing IgA (approximately 3 fold), and leaving IgM and IgG1 unchanged. Since removal of endogenous IL-6 with anti-IL-6 increased serum IgE, and suppressed IgG1 (approximately 50%), with IgM and IgA unchanged, this suggests that IL-6 is an isotype specific suppressor of peak IgE responses and as such may be useful in the therapeutic management of atopic disease. IFN alpha treatment increased serum IgE levels (60%), and potentiated IgA responses (> 30 fold), with IgM and IgG1 unchanged. Since removal of endogenous IFN alpha with anti-IFN alpha decreased IgE levels (approximately 50%), increasing IgA, with IgM and IgG1 unchanged, this suggests a role for IFN alpha as an isotype specific helper of peak IgE responses and in maintenance of IgA responses.

  5. Chikungunya virus neutralization antigens and direct cell-to-cell transmission are revealed by human antibody-escape mutants.

    Directory of Open Access Journals (Sweden)

    Chia Yin Lee

    2011-12-01

    Full Text Available Chikungunya virus (CHIKV is an alphavirus responsible for numerous epidemics throughout Africa and Asia, causing infectious arthritis and reportedly linked with fatal infections in newborns and elderly. Previous studies in animal models indicate that humoral immunity can protect against CHIKV infection, but despite the potential efficacy of B-cell-driven intervention strategies, there are no virus-specific vaccines or therapies currently available. In addition, CHIKV has been reported to elicit long-lasting virus-specific IgM in humans, and to establish long-term persistence in non-human primates, suggesting that the virus might evade immune defenses to establish chronic infections in man. However, the mechanisms of immune evasion potentially employed by CHIKV remain uncharacterized. We previously described two human monoclonal antibodies that potently neutralize CHIKV infection. In the current report, we have characterized CHIKV mutants that escape antibody-dependent neutralization to identify the CHIKV E2 domain B and fusion loop "groove" as the primary determinants of CHIKV interaction with these antibodies. Furthermore, for the first time, we have also demonstrated direct CHIKV cell-to-cell transmission, as a mechanism that involves the E2 domain A and that is associated with viral resistance to antibody-dependent neutralization. Identification of CHIKV sub-domains that are associated with human protective immunity, will pave the way for the development of CHIKV-specific sub-domain vaccination strategies. Moreover, the clear demonstration of CHIKV cell-to-cell transmission and its possible role in the establishment of CHIKV persistence, will also inform the development of future anti-viral interventions. These data shed new light on CHIKV-host interactions that will help to combat human CHIKV infection and inform future studies of CHIKV pathogenesis.

  6. Optimal Cutoff and Accuracy of an IgM Enzyme-Linked Immunosorbent Assay for Diagnosis of Acute Scrub Typhus in Northern Thailand: an Alternative Reference Method to the IgM Immunofluorescence Assay

    Science.gov (United States)

    Blacksell, Stuart D.; Tanganuchitcharnchai, Ampai; Jintaworn, Suthatip; Kantipong, Pacharee; Richards, Allen L.; Day, Nicholas P. J.

    2016-01-01

    The enzyme-linked immunosorbent assay (ELISA) has been proposed as an alternative serologic diagnostic test to the indirect immunofluorescence assay (IFA) for scrub typhus. Here, we systematically determine the optimal sample dilution and cutoff optical density (OD) and estimate the accuracy of IgM ELISA using Bayesian latent class models (LCMs). Data from 135 patients with undifferentiated fever were reevaluated using Bayesian LCMs. Every patient was evaluated for the presence of an eschar and tested with a blood culture for Orientia tsutsugamushi, three different PCR assays, and an IgM IFA. The IgM ELISA was performed for every sample at sample dilutions from 1:100 to 1:102,400 using crude whole-cell antigens of the Karp, Kato, and Gilliam strains of O. tsutsugamushi developed by the Naval Medical Research Center. We used Bayesian LCMs to generate unbiased receiver operating characteristic curves and found that the sample dilution of 1:400 was optimal for the IgM ELISA. With the optimal cutoff OD of 1.474 at a sample dilution of 1:400, the IgM ELISA had a sensitivity of 85.7% (95% credible interval [CrI], 77.4% to 86.7%) and a specificity of 98.1% (95% CrI, 97.2% to 100%) using paired samples. For the ELISA, the OD could be determined objectively and quickly, in contrast to the reading of IFA slides, which was both subjective and labor-intensive. The IgM ELISA for scrub typhus has high diagnostic accuracy and is less subjective than the IgM IFA. We suggest that the IgM ELISA may be used as an alternative reference test to the IgM IFA for the serological diagnosis of scrub typhus. PMID:27008880

  7. Optimal Cutoff and Accuracy of an IgM Enzyme-Linked Immunosorbent Assay for Diagnosis of Acute Scrub Typhus in Northern Thailand: an Alternative Reference Method to the IgM Immunofluorescence Assay.

    Science.gov (United States)

    Blacksell, Stuart D; Lim, Cherry; Tanganuchitcharnchai, Ampai; Jintaworn, Suthatip; Kantipong, Pacharee; Richards, Allen L; Paris, Daniel H; Limmathurotsakul, Direk; Day, Nicholas P J

    2016-06-01

    The enzyme-linked immunosorbent assay (ELISA) has been proposed as an alternative serologic diagnostic test to the indirect immunofluorescence assay (IFA) for scrub typhus. Here, we systematically determine the optimal sample dilution and cutoff optical density (OD) and estimate the accuracy of IgM ELISA using Bayesian latent class models (LCMs). Data from 135 patients with undifferentiated fever were reevaluated using Bayesian LCMs. Every patient was evaluated for the presence of an eschar and tested with a blood culture for Orientia tsutsugamushi, three different PCR assays, and an IgM IFA. The IgM ELISA was performed for every sample at sample dilutions from 1:100 to 1:102,400 using crude whole-cell antigens of the Karp, Kato, and Gilliam strains of O. tsutsugamushi developed by the Naval Medical Research Center. We used Bayesian LCMs to generate unbiased receiver operating characteristic curves and found that the sample dilution of 1:400 was optimal for the IgM ELISA. With the optimal cutoff OD of 1.474 at a sample dilution of 1:400, the IgM ELISA had a sensitivity of 85.7% (95% credible interval [CrI], 77.4% to 86.7%) and a specificity of 98.1% (95% CrI, 97.2% to 100%) using paired samples. For the ELISA, the OD could be determined objectively and quickly, in contrast to the reading of IFA slides, which was both subjective and labor-intensive. The IgM ELISA for scrub typhus has high diagnostic accuracy and is less subjective than the IgM IFA. We suggest that the IgM ELISA may be used as an alternative reference test to the IgM IFA for the serological diagnosis of scrub typhus.

  8. Relationship between the concentration of anti-polyethylene glycol (PEG) immunoglobulin M (IgM) and the intensity of the accelerated blood clearance (ABC) phenomenon against PEGylated liposomes in mice.

    Science.gov (United States)

    Hashimoto, Yosuke; Shimizu, Taro; Abu Lila, Amr Selim; Ishida, Tatsuhiro; Kiwada, Hiroshi

    2015-01-01

    PEGylation, which is the surface modification of nanocarriers with polyethylene glycol (PEG), has increased the circulation time and reduced the immunogenic responses to nanocarriers. However, many reports have demonstrated that the intravenous injection of sterically stabilized PEGylated liposome (SL) causes an accelerated blood clearance (ABC) of subsequent doses via anti-PEG immunoglobulin M (IgM)-mediated complement activation. In the present study, the relationships between serum anti-PEG IgM concentration, the intensity of complement activation and the hepatic clearance of SL were quantitatively investigated for their role in the ABC phenomenon. Interestingly, with increasing serum anti-PEG IgM concentrations, the intensity of complement activation increased linearly, while the intensity of the hepatic clearance of SL was increased and then saturated. In addition, only 15-17% of anti-PEG IgM in blood circulation induced by SL at different doses was associated with a second dose SL. The present results indicate that it is the hepatic uptake of SL that is the limiting step in the ABC phenomenon, rather than the association of anti-PEG IgM to the SL and a subsequent complement activation.

  9. Novel hemagglutinin nanoparticle influenza vaccine with Matrix-M™ adjuvant induces hemagglutination inhibition, neutralizing, and protective responses in ferrets against homologous and drifted A(H3N2) subtypes.

    Science.gov (United States)

    Smith, Gale; Liu, Ye; Flyer, David; Massare, Michael J; Zhou, Bin; Patel, Nita; Ellingsworth, Larry; Lewis, Maggie; Cummings, James F; Glenn, Greg

    2017-09-25

    Influenza viruses frequently acquire mutations undergoing antigenic drift necessitating annual evaluation of vaccine strains. Highly conserved epitopes have been identified in the hemagglutinin (HA) head and stem regions, however, current influenza vaccines induce only limited responses to these conserved sites. Here, we describe a novel seasonal recombinant HA nanoparticle influenza vaccine (NIV) formulated with a saponin-based adjuvant, Matrix-M™. NIV induced hemagglutination inhibition (HAI) and microneutralizing (MN) antibodies against a broad range of influenza A(H3N2) subtypes. In a comparison of NIV against standard-dose and high-dose inactivated influenza vaccines (IIV and IIV-HD, respectively) in ferrets NIV elicited HAI and MN responses exceeding those induced by IIV-HD against homologous A(H3N2) by 7 fold, A(H1N1) by 26 fold, and B strain viruses by 2 fold. NIV also induced MN responses against all historic A/H3N2 strains tested, spanning more than a decade of viral evolution from the 2000-2017 influenza seasons whereas IIV and IIV-HD induced HAI and MN responses were largely directed against the homologous A(H3N2), A(H1N1), and B virus strains. NIV induced superior protection compared to IIV and IIV-HD in ferrets challenged with a homologous or 10-year drifted influenza A(H3N2) strain. HAI positive and HAI negative neutralizing monoclonal antibodies derived from mice immunized with NIV were active against homologous and drifted influenza A(H3N2) strains. Taken together these observations suggest that NIV can induce responses to one or more highly conserved HA head and stem epitopes and result in highly neutralizing antibodies against both homologous and drift strains. Copyright © 2017. Published by Elsevier Ltd.

  10. The new ParaDIgm: IgM from bench to clinic: November 15-16, 2011, Frankfurt, Germany.

    Science.gov (United States)

    Hanala, Sherif

    2012-01-01

    The inaugural IgM event entitled "The new ParaDIgm: IgM from bench to clinic" brought together the increasingly active and growing IgM antibody community to discuss recent advances and challenges facing the discovery and development of IgM antibody therapies and technologies. Researchers, clinicians and biomanufacturing experts delivered 21 talks on the basic science and isolation of IgM, upstream and downstream development, and formulation and clinical development of the molecules. Participants networked around topics aimed at exploring the full potential of IgM antibodies. The meeting was held at DECHEMA Gesellschaft für Chemische Technik und Biotechnologie e. V. (Society for Chemical Engineering and Biotechnology), a non-profit scientific and technical society based in Frankfurt am Main, Germany. The meeting was sponsored by Patrys, Laureate Biopharma, Bio-Rad Laboratories, BIA Separations, Percivia and the Bio Affinity Company (BAC). The second New ParaDIgm: IgM from bench to clinic meeting, will be held on April 23-24, 2013 in Frankfurt, Germany.

  11. Architecture of Human IgM in Complex with P. falciparum Erythrocyte Membrane Protein 1

    Directory of Open Access Journals (Sweden)

    Reetesh Raj Akhouri

    2016-02-01

    Full Text Available Plasmodium falciparum virulence is associated with sequestration of infected erythrocytes. Microvascular binding mediated by PfEMP1 in complex with non-immune immunoglobulin M (IgM is common among parasites that cause both severe childhood malaria and pregnancy-associated malaria. Here, we present cryo-molecular electron tomography structures of human IgM, PfEMP1 and their complex. Three-dimensional reconstructions of IgM reveal that it has a dome-like core, randomly oriented Fab2s units, and the overall shape of a turtle. PfEMP1 is a C- shaped molecule with a flexible N terminus followed by an arc-shaped backbone and a bulky C terminus that interacts with IgM. Our data demonstrate that the PfEMP1 binding pockets on IgM overlap with those of C1q, and the bulkiness of PfEMP1 limits the capacity of IgM to interact with PfEMP1. We suggest that P. falciparum exploits IgM to cluster PfEMP1 into an organized matrix to augment its affinity to host cell receptors.

  12. Helium Reionization Simulations. II. Signatures of Quasar Activity on the IGM

    CERN Document Server

    La Plante, Paul; Croft, Rupert; Cen, Renyue

    2016-01-01

    We have run a new suite of simulations that solve hydrodynamics and radiative transfer simultaneously to study helium II reionization. Our suite of simulations employs various models for populating quasars inside of dark matter halos, which affect the He II reionization history. In particular, we are able to explore the impact that differences in the timing and duration of reionization have on observables. We examine the thermal signature that reionization leaves on the IGM, and measure the temperature-density relation. As previous studies have shown, we confirm that the photoheating feedback from helium II reionization raises the temperature of the IGM by several thousand kelvin. To compare against observations, we generate synthetic Lyman-$\\alpha$ forest sightlines on-the-fly and match the observed effective optical depth $\\tau_{\\mathrm{eff}}(z)$ of hydrogen to recent observations. We show that when the simulations have been normalized to have the same values of $\\tau_\\mathrm{eff}$, the effect that helium I...

  13. Cosmic Reionization On Computers. Properties of the Post-reionization IGM

    Energy Technology Data Exchange (ETDEWEB)

    Gnedin, Nickolay Y. [Fermilab; Becker, George D. [Baltimore, Space Telescope Sci.; Fan, Xiaohui [Arizona U., Astron. Dept. - Steward Observ.

    2016-05-10

    We present a comparison between several observational tests of the post-reionization IGM and the numerical simulations of reionization completed under the Cosmic Reionization On Computers (CROC) project. We show that CROC simulations reproduce "out-of-the-box" the observed distributions of Gunn-Peterson optical depths, underscoring the importance of self-consistent modeling of radiative transfer. We also show that CROC simulations match well the observed distributions of dark gaps from SDSS quasars. Finally, we introduce a novel statistical probe of the small-scale structure in the IGM: heights and widths of transmission peaks. Simulations match the peak height distributions reasonably well, but do not reproduce the observed abundance of wide peaks.

  14. Cosmic Reionization On Computers. Properties of the Post-reionization IGM

    CERN Document Server

    Gnedin, Nickolay Y; Fan, Xiaohui

    2016-01-01

    We present a comparison between several observational tests of the post-reionization IGM and the numerical simulations of reionization completed under the Cosmic Reionization On Computers (CROC) project. We show that CROC simulations reproduce "out-of-the-box" the observed distributions of Gunn-Peterson optical depths, underscoring the importance of self-consistent modeling of radiative transfer. We also show that CROC simulations match well the observed distributions of dark gaps from SDSS quasars. Finally, we introduce a novel statistical probe of the small-scale structure in the IGM: heights and widths of transmission peaks. Simulations match the peak height distributions reasonably well, but do not reproduce the observed abundance of wide peaks.

  15. Experiences Integrating Transmission and Distribution Simulations for DERs with the Integrated Grid Modeling System (IGMS)

    Energy Technology Data Exchange (ETDEWEB)

    Palmintier, Bryan; Hale, Elaine; Hodge, Bri-Mathias; Baker, Kyri; Hansen, Timothy M.

    2016-08-11

    This paper discusses the development of, approaches for, experiences with, and some results from a large-scale, high-performance-computer-based (HPC-based) co-simulation of electric power transmission and distribution systems using the Integrated Grid Modeling System (IGMS). IGMS was developed at the National Renewable Energy Laboratory (NREL) as a novel Independent System Operator (ISO)-to-appliance scale electric power system modeling platform that combines off-the-shelf tools to simultaneously model 100s to 1000s of distribution systems in co-simulation with detailed ISO markets, transmission power flows, and AGC-level reserve deployment. Lessons learned from the co-simulation architecture development are shared, along with a case study that explores the reactive power impacts of PV inverter voltage support on the bulk power system.

  16. Diversity and repertoire of IgW and IgM VH families in the newborn nurse shark

    Directory of Open Access Journals (Sweden)

    Dooley Helen

    2004-05-01

    Full Text Available Abstract Background Adult cartilaginous fish express three immunoglobulin (Ig isotypes, IgM, IgNAR and IgW. Newborn nurse sharks, Ginglymostoma cirratum, produce 19S (multimeric IgM and monomeric/dimeric IgM1gj, a germline-joined, IgM-related VH, and very low amounts of 7S (monomeric IgM and IgNAR proteins. Newborn IgNAR VH mRNAs are diverse in the complementarity-determining region 3 (CDR3 with non-templated nucleotide (N-region addition, which suggests that, unlike in many other vertebrates, terminal deoxynucleotidyl transferase (TdT expressed at birth is functional. IgW is present in the lungfish, a bony fish sharing a common ancestor with sharks 460 million years ago, implying that the IgW VH family is as old as the IgM VH family. This nurse shark study examined the IgM and IgW VH repertoire from birth through adult life, and analyzed the phylogenetic relationships of these gene families. Results IgM and IgW VH cDNA clones isolated from newborn nurse shark primary and secondary lymphoid tissues had highly diverse and unique CDR3 with N-region addition and VDJ gene rearrangement, implicating functional TdT and RAG gene activity. Despite the clear presence of N-region additions, newborn CDR3 were significantly shorter than those of adults. The IgM clones are all included in a conventional VH family that can be classified into five discrete groups, none of which is orthologous to IgM VH genes in other elasmobranchs. In addition, a novel divergent VH family was orthologous to a published monotypic VH horn shark family. IgW VH genes have diverged sufficiently to form three families. IgM and IgW VH serine codons using the potential somatic hypermutation hotspot sequence occur mainly in VH framework 1 (FR1 and CDR1. Phylogenetic analysis of cartilaginous fish and lungfish IgM and IgW demonstrated they form two major ancient gene groups; furthermore, these VH genes generally diversify (duplicate and diverge within a species. Conclusion As in ratfish

  17. Nogo stimuli do not receive more attentional suppression or response inhibition than neutral stimuli: evidence from the N2pc, PD and N2 components in a spatial cueing paradigm

    Directory of Open Access Journals (Sweden)

    Caroline eBarras

    2016-05-01

    Full Text Available It has been claimed that stimuli sharing the color of the nogo-target are suppressed because of the strong incentive to not process the nogo-target, but we failed to replicate this finding. Participants searched for a color singleton in the target display and indicated its shape when it was in the go color. If the color singleton in the target display was in the nogo color, they had to withhold the response. The target display was preceded by a cue display that also contained a color singleton (the cue. The cue was either in the color of the go or nogo target, or it was in an unrelated, neutral color. With cues in the go color, reaction times (RTs were shorter when the cue appeared at the same location as the target compared to when it appeared at a different location. Also, electrophysiological recordings showed that an index of attentional selection, the N2pc, was elicited by go cues. Surprisingly, we failed to replicate cueing costs for cues in the nogo color that were originally reported by Anderson and Folk (2012. Consistently, we also failed to find an electrophysiological index of attentional suppression (the PD for cues in the nogo color. Further, fronto-central ERPs to the cue display showed the same negativity for nogo and neutral stimuli relative to go stimuli, which is at odds with response inhibition and conflict monitoring accounts of the Nogo-N2. Thus, the modified cueing paradigm employed here provides little evidence that features associated with nogo-targets are suppressed at the level of attention or response selection. Rather, nogo-stimuli are efficiently ignored and attention is focused on features that require a response.

  18. IgM MGUS anti-MAG neuropathy with predominant muscle weakness and extensive muscle atrophy.

    Science.gov (United States)

    Kawagashira, Yuichi; Kondo, Naohide; Atsuta, Naoki; Iijima, Masahiro; Koike, Haruki; Katsuno, Masahisa; Tanaka, Fumiaki; Kusunoki, Susumu; Sobue, Gen

    2010-09-01

    We report a patient with anti-myelin-associated glycoprotein (MAG) neuropathy, predominantly exhibiting severe motor symptoms, accompanied by extensive muscle atrophy mimicking Charcot-Marie-Tooth disease. Nerve conduction studies revealed mild retardation of motor conduction velocities and significant prolongation of distal latency. Sural nerve biopsy revealed widely spaced myelin and positive staining of myelinated fibers with an IgM antibody. Predominant motor symptoms with muscle atrophy can be one of the clinical manifestations of anti-MAG neuropathy.

  19. IgM anti-GM1 antibody titers in patients with monomelic amyotrophy

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    Khandelwal Dinesh

    2006-01-01

    Full Text Available Background: Monomelic amyotrophy (MMA is a benign motor neuron disorder, which particularly affects young people and the etiology is still unknown. Gangliosides are located on the outer surface of motor neurons. Anti-GM1 antibodies have been found to be elevated in multi-focal motor neuropathy with conduction block and other neurological diseases, which may have therapeutic implication. Aim: To evaluate IgM anti-GM1 antibody titers in patients of monomelic amyotrophy. Setting and Design: prospective controlled study. Materials and Methods: Forty-six clinically and electrophysiologically diagnosed cases of MMA were assessed for IgM anti-GM1 antibody titers by enzyme-linked immunosorbent assay (ELISA method and compared with titers in healthy controls, cases of amyotrophic lateral sclerosis (ALS and acute inflammatory demyelinating polyneuropathy (AIDP. Titer of 800 units was taken as upper limit of normal (Buhlmann Laboratories AG, Switzerland. Statistical Analysis Used: one-way ANOVA. Results: The mean age of 46 patients with MMA was 24.5 (± 7.3 years, with male female ratio of 44:2. The mean age of 19 healthy controls was 24.1 (± 3 years with male: female ratio of 18:1. Five (26% individuals in the healthy control group, 22 (48% patients of MMA, four (30% of ALS and five (50% of AIDP had high titers of IgM anti-GM1 antibody ( P >0.05. Conclusions: Although larger number of patients with MMA had higher IgM anti-GM1 antibody titers, the difference was not statistically significant from titers of healthy individuals, and of patients in the ALS and AIDP group.

  20. Chlamydia trachomatis IgM seropositivity during pregnancy and assessment of its risk factors.

    Science.gov (United States)

    Rahman, M; Chowdhury, S B; Akhtar, N; Jahan, M; Jahan, M K; Jebunnahar, S

    2014-01-01

    The study was undertaken to determine socio-demographic and reproductive risk factors associated with Chlamydia trachomaties IgM seropositivity during pregnancy. This cross sectional comparative study was carried out in the obstetrics outdoor of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh in collaboration with the department of Virology between the periods from July 2007 to December 2008. Pregnant women at their first visit to the hospital were approached consecutively and asked to complete a questionnaire and 2cc blood was collected from each subject for Chlamydia trachomatis IgM antibody testing using ELISA method. The study population was divided into two groups according to the presence and absence of serum Chlamydia trachomatis IgM antibody. Finally socio-demographic and reproductive risk factors were compared between the groups. Among 172 women the sero-prevalence of Chlamydia IgM was 41%. The multiple logistic regression model (step wise) finally extracted for characteristics correlated with seropositivity. Ten years or less (≤SSC) education (OR 2.6 95% CI 1.1to 5.9), history of adverse pregnancy outcome (OR 2.8 95% CI 1.2 to 6.5) and multiple sex partner of husband (OR 4.1 95% CI 1.2 to 14.8) were associated with chlamydia infection. The use of condom (OR 0.28 95% CI 0.12 to 0.63) was associated with decreased risk of infection. Chlamydia trachomatis infection during pregnancy is associated with risk factors on the basis of which selective screening can be done.

  1. An HST/COS Survey of the Low-Redshift IGM. I. Survey, Methodology, & Overall Results

    CERN Document Server

    Danforth, Charles W; Shull, J Michael; Keeney, Brian A; Stevans, Matthew; Pieri, Matthew M; Stocke, John T; Savage, Blair D; France, Kevin; Syphers, David; Smith, Britton D; Green, James C; Froning, Cynthia; Penton, Steven V; Osterman, Steven N

    2014-01-01

    We use high-quality, medium-resolution HST/COS observations of 75 UV-bright AGN at redshifts $z_{\\rm AGN}10^{13.5}~\\rm cm^{-2}$) absorbers particularly those with metal absorption. The full catalog of absorption lines and fully-reduced spectra is available via MAST as a high-level science product at http://archive.stsci.edu/prepds/igm/.

  2. Comparison of chemiluminescent immunoassay and ELISA for measles IgG and IgM.

    Science.gov (United States)

    de Ory, Fernando; Minguito, Teodora; Balfagón, Pilar; Sanz, Juan C

    2015-08-01

    In the context of measles elimination, the identification of recent infections is important for clinical laboratories. Serological diagnosis is achieved by detecting specific IgG and IgM. Recently an automated chemiluminescent immunoassay (CLIA) (Liaison, DiaSorin, Italy) has been used to quantify the measles antibody. The aim of this study was to compare this assay with Enzygnost ELISA (Siemens, Germany), with final classification of discrepancies by indirect immunofluorescence (Euroimmun, Germany). For measles IgM, 204 sera were analyzed: 50 IgM-positive, 104 IgM-negative/IgG-positive, and 50 from other viral infections (B19V, rubella, mumps, CMV, and EBV). For the measles IgG assay, 162 samples were tested: 106 were positive and 56 were negative. For measles IgM, the sensitivity and specificity of CLIA against ELISA were 94% (95% CI: 83.2-98.6) and 100% (95% CI: 97.1-100), respectively; the corrected figures after the final classification of discrepancies were 100% (95% CI: 91.0-100) and 99.4% (95% CI: 96.1-100), respectively. In relation to IgG, the sensitivity and specificity of CLIA against ELISA were, respectively, 97.2% (95% CI: 91.7-99.4) and 92.9% (95% CI: 82.5-97.7), and 95.5% (95% CI: 89.5-98.3) and 100% (95% CI: 91.8-100) after the final classification. CLIA showed excellent sensitivity and specificity in detecting measles IgG and IgM antibodies, eliminating the need to aliquot specimens before carrying out the assay.

  3. Toxoplasmosis serology: an efficient hemagglutination procedure to detect IgG and IgM antibodies

    Directory of Open Access Journals (Sweden)

    M.E. Camargo

    1989-08-01

    Full Text Available In search of an efficient but simple, low cost procedure for the serodiagnosis of Toxoplasmosis, especially suited for routine laboratories facing technical and budget limitations as in less developed countries, the diagnostic capability of Hematoxo® , an hemagglutination test for toxoplasmosis, was evaluated in relation to a battery of tests including IgG- and IgM-immunofluorescence tests, hemagglutination and an IgM-capture enzymatic assay. Detecting a little as 5 I.U. of IgG antitoxoplasma antibodies, Hematoxo® showed a straight agreement as to reactivity and non-reactivity for the 443 non-reactive and the 387 reactive serum samples, included in this study. In 23 cases presenting a serological pattern of acute toxoplasmosis and showing IgM antibodies, Hematoxo® could detect IgM antibodies in 18, indicated by negativation or a significant decrease in titers as a result of treating samples with 2-mercapto-ethanol. However, a neat increase in sensitivity for IgM specific antibodies could be achieved by previously removing IgG from the sample, as demonstrated in a series of acute toxoplasmosis sera. A simple procedure was developed for this purpose, by reconstituting a lyophilized suspension of Protein A - rich Staphylococcus with the lowest serum dilution to be tested. Of low cost and easy to perform, Hematoxo® affords not only a practical qualitative procedure for screening reactors and non-reactors, as in prenatal services, but also quantitative assays that permit to titrate antibodies as well as to identify IgM antibodies.

  4. Role of membrane-bound IgM in Trypanosoma cruzi evasion from immune clearance.

    Science.gov (United States)

    Garcia, I E; Lima, M R; Marinho, C R; Kipnis, T L; Furtado, G C; Alvarez, J M

    1997-04-01

    We have recently described that Trypanosoma cruzi parasites of the reticulotropic Y strain increase their resistance to antibody-induced clearance during their interaction with the vertebrate host immune system. In the present study, we observed that trypomastigotes of the myotropic CL strain isolated from normal host also display an increased resistance to immune clearance when compared to parasites obtained from immunosuppressed donors. Through fluorescence-activated cell sorting analysis, we have observed that the high expression of membrane-bound IgM antibodies on Y and CL trypomastigotes correlates with their enhanced resistance to Ig-induced clearance. Trypomastigotes from normal mice were essentially refractory to the in vitro binding of immunoglobulins, showing that their membrane structures were completely covered by IgM antibodies. These findings suggest that this isotype does not efficiently mediate immune clearance. Moreover, membrane-bound IgM antibodies limited the amount of IgG attached to the parasite and, as a consequence, impaired efficient immune clearance. Through this mechanism, trypomastigotes of T. cruzi could increase their persistence in the bloodstream thus favoring parasite transmission to its hematophagous host vector in the early acute phase of the disease.

  5. IgM multiple myeloma with an extremely rare non-aggressive presentation: A case report.

    Science.gov (United States)

    Greuter, Thomas; Browne, Martin; Dommann-Scherrer, Corina; Binder, Daniel; Renner, Christoph; Kapp, Ursula

    2016-10-01

    In the present study, the case of a 41-year-old man with immunoglobulin (Ig)M multiple myeloma (MM) that presented with an unusually non-aggressive clinical course who has survived for >9 years to date, is presented. Initial diagnosis of symptomatic MM was established according to the International Myeloma Working Group consensus statement and guidelines. Due to the mild symptoms, no therapy was administered and the patient was closely followed up. Eight years after initial diagnosis, clinical, morphological and genetic progression occurred with the development of hypercalcemia, progressively deteriorating polyneuropathy, clonal expansion of plasma cells up to 50% of hematopoietic cells and demonstration of the typical t(11;14) translocation (Ig heavy chain locus rearrangement). Subsequently, 4 cycles of induction chemotherapy with velcade, cyclophosphamide and dexamethasone, were administered. At the time of writing, the patient remained alive in generally good health. To the best of our knowledge, with a survival time of >9 years, this case reports the longest survival time of an IgM MM patient to date, which contradicts previous evidence that suggests IgM MM exhibits an aggressive clinical course.

  6. Stabilitas Imunoglobulin M (IgM Campak pada Dried Serum Spots

    Directory of Open Access Journals (Sweden)

    Kartika Dewi Puspa

    2015-05-01

    Full Text Available Shipping and storage of measles serum specimens from fields to the reference laboratory must consider the cold chain in order to maintain the stability of immunoglobulin M (IgM in serum. Meanwhile, to maintain the cold chain needs special handling. This study aimed to determine the use of filter paper as an alternative in shipping and storage of specimens. This experimental study used measles positive serum received at the National Measles Laboratory Center for Biomedical and Basic Technology of Health from January until March 2011. There were three groups of sample. Each group consisted of 9 specimens. The effects of temperature and storage period on the stability of measles IgM of dried serum spots (DSS stored in 4°C and 25°C for one, three, six, nine, twelve, and five teen days were tested at the National Measles Laboratory Center for Biomedical and Basic Technology of Health from July until December 2011. The stability of measles IgM of DSS that were stored at 4°C and 25°C temperature showed no significant difference (p = 0.316 compared to the serums stored at a temperature of 4°C in the measurements on the third day. Dried serum spots can not be used as sample alternative for detection of measles virus-spesific immunoglobulin M

  7. Hyper IgM syndrome presenting as chronic suppurative lung disease

    Directory of Open Access Journals (Sweden)

    Montella Silvia

    2012-09-01

    Full Text Available Abstract The Hyper-immunoglobulin M syndromes (HIGM are a heterogeneous group of genetic disorders resulting in defects of immunoglobulin class switch recombination. Affected patients show humoral immunodeficiency and high susceptibility to opportunistic infections. Elevated serum IgM levels are the hallmark of the disease, even though in few rare cases they may be in the normal range. Hyper IgM is associated with low to undetectable levels of serum IgG, IgA, and IgE. In some cases, alterations in different genes may be identified. Mutations in five genes have so far been associated to the disease, which can be inherited with an X-linked (CD40 ligand, and nuclear factor-kB essential modulator defects or an autosomal recessive (CD40, activation-induced cytidine deaminase, and uracil-DNA glycosylase mutation pattern. The patient herein described presented with recurrent upper and lower respiratory infections and evidence of suppurative lung disease at the conventional chest imaging. The presence of low serum IgG and IgA levels, elevated IgM levels, and a marked reduction of in vivo switched memory B cells led to a clinical and functional diagnosis of HIGM although the genetic cause was not identified.

  8. Transgenic mouse model of IgM+ lymphoproliferative disease mimicking Waldenström macroglobulinemia

    Science.gov (United States)

    Tompkins, V S; Sompallae, R; Rosean, T R; Walsh, S; Acevedo, M; Kovalchuk, A L; Han, S-S; Jing, X; Holman, C; Rehg, J E; Herms, S; Sunderland, J S; Morse, H C; Janz, S

    2016-01-01

    Waldenström macroglobulinemia (WM) is a low-grade incurable immunoglobulin M+ (IgM+) lymphoplasmacytic lymphoma for which a genetically engineered mouse model of de novo tumor development is lacking. On the basis of evidence that the pro-inflammatory cytokine, interleukin 6 (IL6), and the survival-enhancing oncoprotein, B cell leukemia 2 (BCL2), have critical roles in the natural history of WM, we hypothesized that the enforced expression of IL6 and BCL2 in mice unable to perform immunoglobulin class switch recombination may result in a lymphoproliferative disease that mimics WM. To evaluate this possibility, we generated compound transgenic BALB/c mice that harbored the human BCL2 and IL6 transgenes, EμSV-BCL2-22 and H2-Ld-hIL6, on the genetic background of activation-induced cytidine deaminase (AID) deficiency. We designated these mice BCL2+IL6+AID− and found that they developed—with full genetic penetrance (100% incidence) and suitably short latency (93 days median survival)—a severe IgM+ lymphoproliferative disorder that recapitulated important features of human WM. However, the BCL2+IL6+AID− model also exhibited shortcomings, such as low serum IgM levels and histopathological changes not seen in patients with WM, collectively indicating that further refinements of the model are required to achieve better correlations with disease characteristics of WM. PMID:27813533

  9. Hydrophobin fusion of an influenza virus hemagglutinin allows high transient expression in Nicotiana benthamiana, easy purification and immune response with neutralizing activity.

    Directory of Open Access Journals (Sweden)

    Nicolas Jacquet

    Full Text Available The expression of recombinant hemagglutinin in plants is a promising alternative to the current egg-based production system for the influenza vaccines. Protein-stabilizing fusion partners have been developed to overcome the low production yields and the high downstream process costs associated with the plant expression system. In this context, we tested the fusion of hydrophobin I to the hemagglutinin ectodomain of the influenza A (H1N1pdm09 virus controlled by the hybrid En2PMA4 transcriptional promoter to rapidly produce high levels of recombinant antigen by transient expression in agro-infiltrated Nicotiana benthamiana leaves. The fusion increased the expression level by a factor of ∼ 2.5 compared to the unfused protein allowing a high accumulation level of 8.6% of the total soluble proteins. Hemagglutinin was located in ER-derived protein bodies and was successfully purified by combining an aqueous-two phase partition system and a salting out step. Hydrophobin interactions allowed the formation of high molecular weight hemagglutinin structures, while unfused proteins were produced as monomers. Purified protein was shown to be biologically active and to induce neutralizing antibodies after mice immunization. Hydrophobin fusion to influenza hemagglutinin might therefore be a promising approach for rapid, easy, and low cost production of seasonal or pandemic influenza vaccines in plants.

  10. Mucosal Immunization Induces a Higher Level of Lasting Neutralizing Antibody Response in Mice by a Replication-Competent Smallpox Vaccine: Vaccinia Tiantan Strain

    Directory of Open Access Journals (Sweden)

    Bin Lu

    2011-01-01

    Full Text Available The possible bioterrorism threat using the variola virus, the causative agent of smallpox, has promoted us to further investigate the immunogenicity profiles of existing vaccines. Here, we study for the first time the immunogenicity profile of a replication-competent smallpox vaccine (vaccinia Tiantan, VTT strain for inducing neutralizing antibodies (Nabs through mucosal vaccination, which is noninvasive and has a critical implication for massive vaccination programs. Four different routes of vaccination were tested in parallel including intramuscular (i.m., intranasal (i.n., oral (i.o., and subcutaneous (s.c. inoculations in mice. We found that one time vaccination with an optimal dose of VTT was able to induce anti-VTT Nabs via each of the four routes. Higher levels of antiviral Nabs, however, were induced via the i.n. and i.o. inoculations when compared with the i.m. and s.c. routes. Moreover, the i.n. and i.o. vaccinations also induced higher sustained levels of Nabs overtime, which conferred better protections against homologous or alternating mucosal routes of viral challenges six months post vaccination. The VTT-induced immunity via all four routes, however, was partially effective against the intramuscular viral challenge. Our data have implications for understanding the potential application of mucosal smallpox vaccination and for developing VTT-based vaccines to overcome preexisting antivaccinia immunity.

  11. Mucosal immunization induces a higher level of lasting neutralizing antibody response in mice by a replication-competent smallpox vaccine: vaccinia Tiantan strain.

    Science.gov (United States)

    Lu, Bin; Yu, Wenbo; Huang, Xiaoxing; Wang, Haibo; Liu, Li; Chen, Zhiwei

    2011-01-01

    The possible bioterrorism threat using the variola virus, the causative agent of smallpox, has promoted us to further investigate the immunogenicity profiles of existing vaccines. Here, we study for the first time the immunogenicity profile of a replication-competent smallpox vaccine (vaccinia Tiantan, VTT strain) for inducing neutralizing antibodies (Nabs) through mucosal vaccination, which is noninvasive and has a critical implication for massive vaccination programs. Four different routes of vaccination were tested in parallel including intramuscular (i.m.), intranasal (i.n.), oral (i.o.), and subcutaneous (s.c.) inoculations in mice. We found that one time vaccination with an optimal dose of VTT was able to induce anti-VTT Nabs via each of the four routes. Higher levels of antiviral Nabs, however, were induced via the i.n. and i.o. inoculations when compared with the i.m. and s.c. routes. Moreover, the i.n. and i.o. vaccinations also induced higher sustained levels of Nabs overtime, which conferred better protections against homologous or alternating mucosal routes of viral challenges six months post vaccination. The VTT-induced immunity via all four routes, however, was partially effective against the intramuscular viral challenge. Our data have implications for understanding the potential application of mucosal smallpox vaccination and for developing VTT-based vaccines to overcome preexisting antivaccinia immunity.

  12. New Limits on 21cm EoR From PAPER-32 Consistent with an X-Ray Heated IGM at z=7.7

    CERN Document Server

    Parsons, Aaron R; Aguirre, James E; Ali, Zaki S; Bradley, Richard F; Carilli, Chris L; DeBoer, David R; Dexter, Matthew R; Gugliucci, Nicole E; Jacobs, Daniel C; Klima, Pat; MacMahon, David H E; Manley, Jason R; Moore, David F; Pober, Jonathan C; Stefan, Irina I; Walbrugh, William P

    2013-01-01

    We present new constraints on the 21cm Epoch of Reionization (EoR) power spectrum derived from 3 months of observing with a 32-antenna, dual-polarization deployment of the Donald C. Backer Precision Array for Probing the Epoch of Reionization (PAPER) in South Africa. In this paper, we demonstrate the efficacy of the delay-spectrum approach to avoiding foregrounds, achieving over 8 orders of magnitude of foreground suppression (in mK^2). Combining this approach with a procedure for removing off-diagonal covariances arising from instrumental systematics, we achieve a best 2-sigma upper limit of 52 mK^2 for k=0.11 h Mpc^-1 at z=7.7. This limit falls within an order of magnitude of the brighter predictions of the expected 21cm EoR signal level. Using the upper limits set by these measurements, we generate new constraints on the brightness temperature of 21cm emission in neutral regions for various reionization models. We show that for several ionization models, heating of the neutral intergalactic medium (IGM) is...

  13. Neutral particle lithography

    Science.gov (United States)

    Craver, Barry Paul

    Neutral particle lithography (NPL) is a high resolution, proximity exposure technique where a broad beam of energetic neutral particles floods a stencil mask and transmitted beamlets transfer the mask pattern to resist on a substrate, such that each feature is printed in parallel, rather than in the serial manner of electron beam lithography. It preserves the advantages of ion beam lithography (IBL), including extremely large depth-of-field, sub-5 nm resist scattering, and the near absence of diffraction, yet is intrinsically immune to charge-related artifacts including line-edge roughness and pattern placement errors due to charge accumulation on the mask and substrate. In our experiments, a neutral particle beam is formed by passing an ion beam (e.g., 30 keV He+) through a high pressure helium gas cell (e.g., 100 mTorr) to convert the ions to energetic neutrals through charge transfer scattering. The resolution of NPL is generally superior to that of IBL for applications involving insulating substrates, large proximity gaps, and ultra-small features. High accuracy stepped exposures with energetic neutral particles, where magnetic or electrostatic deflection is impossible, have been obtained by clamping the mask to the wafer, setting the proximity gap with a suitable spacer, and mechanically inclining the mask/wafer stack relative to the beam. This approach is remarkably insensitive to vibration and thermal drift; nanometer scale image offsets have been obtained with +/-2 nm placement accuracy for experiments lasting over one hour. Using this nanostepping technique, linewidth versus dose curves were obtained, from which the NPL lithographic blur was determined as 4.4+/-1.4 nm (1sigma), which is 2-3 times smaller than the blur of electron beam lithography. Neutral particle lithography has the potential to form high density, periodic patterns with sub-10 nm resolution.

  14. A triclade DNA vaccine designed on the basis of a comprehensive serologic study elicits neutralizing antibody responses against all clades and subclades of highly pathogenic avian influenza H5N1 viruses.

    Science.gov (United States)

    Zhou, Fan; Wang, Guiqin; Buchy, Philippe; Cai, Zhipeng; Chen, Honglin; Chen, Zhiwei; Cheng, Genhong; Wan, Xiu-Feng; Deubel, Vincent; Zhou, Paul

    2012-06-01

    Because of their rapid evolution, genetic diversity, broad host range, ongoing circulation in birds, and potential human-to-human transmission, H5N1 influenza viruses remain a major global health concern. Their high degree of genetic diversity also poses enormous burdens and uncertainties in developing effective vaccines. To overcome this, we took a new approach, i.e., the development of immunogens based on a comprehensive serologic study. We constructed DNA plasmids encoding codon-optimized hemagglutinin (HA) from 17 representative strains covering all reported clades and subclades of highly pathogenic avian influenza H5N1 viruses. Using DNA plasmids, we generated the corresponding H5N1 pseudotypes and immune sera. We performed an across-the-board pseudotype-based neutralization assay and determined antigenic clusters by cartography. We then designed a triclade DNA vaccine and evaluated its immunogenicity and protection in mice. We report here that (sub)clades 0, 1, 3, 4, 5, 6, 7.1, and 9 were grouped into antigenic cluster 1, (sub)clades 2.1.3.2, 2.3.4, 2.4, 2.5, and 8 were grouped into another antigenic cluster, with subclade 2.2.1 loosely connected to it, and each of subclades 2.3.2.1 and 7.2 was by itself. Importantly, the triclade DNA vaccine encoding HAs of (sub)clades 0, 2.3.2.1, and 7.2 elicited broadly neutralizing antibody responses against all H5 clades and subclades and protected mice against high-lethal-dose heterologous H5N1 challenge. Thus, we conclude that broadly neutralizing antibodies against all H5 clades and subclades can indeed be elicited with immunogens on the basis of a comprehensive serologic study. Further evaluation and optimization of such an approach in ferrets and in humans is warranted.

  15. Circulating Natural IgM Antibodies Against Angiogenin in the Peripheral Blood Sera of Patients with Osteosarcoma as Candidate Biomarkers and Reporters of Tumorigenesis

    Science.gov (United States)

    Savitskaya, Yulia A.; Rico, Genaro; Linares, Luis; González, Roberto; Téllez, René; Estrada, Eréndira; Marín, Norma; Martínez, Elisa; Alfaro, Alfonso; Ibarra, Clemente

    2010-01-01

    Background: Tumor immunology research has led to the identification of a number of tumor-associated self antigens, suggesting that most tumors trigger an immunogenic response, as is the case in osteosarcoma, where the detection of natural serum IgM antibodies might achieve the diagnosis of osteosarcoma. Natural IgM antibodies to tumor-associated proteins may expand the number of available tumor biomarkers for osteosarcoma and may be used together in a serum profile to enhance test sensitivity and specificity. Natural IgM antibodies can be consistently detected in the peripheral blood sera months to years before the tumor is diagnosed clinically. The study of the level of a potential biomarker many months (or years) prior to diagnosis is fundamentally important. Integrated circulating and imaging markers in clinical practice treating osteosarcoma have potential applications for controlling tumor angiogenesis. Objectives: To study the expression of natural IgM antibodies to the tumor antigens of angiogenesis in the peripheral blood sera of osteosarcoma patients and healthy individuals, and to develop serum-based predictive biomarkers. Methods: Peripheral venous blood samples were collected from 117 osteosarcoma patients and 117 patients with other tumors. All diagnosis was histologically confirmed. Staging of patients was performed according to the Enneking Surgical Staging System. The control group consisted of 117 age- and sex- matched healthy individuals. In this study, novel immunoconjugates were designed, synthesized and then used to develop a rapid, specific and sensitive enzyme-linked immunosorbent assay (ELISA) method to detect angiogenin (ANG)–IgM directly in the peripheral blood sera of humans. Results: Serum ANG–IgM levels are significantly higher in osteosarcoma patients than in healthy individuals (P osteosarcoma patients and ANG–IgM levels were significantly higher in osteosarcoma patients compared to any other tumors (P osteosarcoma patients than

  16. A novel trivalent HPV 16/18/58 vaccine with anti-HPV 16 and 18 neutralizing antibody responses comparable to those induced by the Gardasil quadrivalent vaccine in rhesus macaque model.

    Science.gov (United States)

    Yin, Fei; Wang, Yajun; Chen, Na; Jiang, Dunquan; Qiu, Yefeng; Wang, Yan; Yan, Mei; Chen, Jianping; Zhang, Haijiang; Liu, Yongjiang

    2017-06-01

    Persistent infection with human papillomavirus (HPV) is a key factor in the development of precancerous lesions and invasive cervical cancer. Prophylactic vaccines to immunize against HPV are an effective approach to reducing HPV related disease burden. In this study, we investigated the immunogenicity and dosage effect of a trivalent HPV 16/18/58 vaccine (3vHPV) produced in Escherichia coli (E.coli), with Gardasil quadrivalent vaccine (4vHPV, Merck & Co.) as a positive control. Sera collected from rhesus macaques vaccinated with three dosage formulations of 3vHPV (termed low-, mid-, and high-dosage formulations, respectively), and the 4vHPV vaccine were analyzed by both Pseudovirus-Based Neutralization Assay (PBNA) and Enzyme-Linked Immunosorbent Assay (ELISA). Strong immune responses against HPV 16/18/58 were successfully elicited, and dosage-dependence was observed, with likely occurrence of immune interference between different L1-VLP antigens. HPV 16/18 specific neutralizing antibody (nAb) and total immunoglobulin G (IgG) antibody responses in rhesus macaques receiving 3vHPV at the three dosages tested were generally non-inferior to those observed in rhesus macaques receiving 4vHPV throughout the study period. Particularly, HPV 18 nAb titers induced by the mid-dosage formulation that contained the same amounts of HPV 16/18 L1-VLPs as Gardasil 4vHPV were between 7.3 to 12.7-fold higher compared to the positive control arm from weeks 24-64. The durability of antibody responses specific to HPV 16/18 elicited by 3vHPV vaccines was also shown to be non-inferior to that associated with Gardasil 4vHPV. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  17. IgM, IgG and IgA rheumatoid factors and circulating immune complexes in patients with AIDS and AIDS-related complex with serological abnormalities.

    Science.gov (United States)

    Procaccia, S; Lazzarin, A; Colucci, A; Gasparini, A; Forcellini, P; Lanzanova, D; Foppa, C U; Novati, R; Zanussi, C

    1987-01-01

    To investigate some humoral aspects which may reflect the involvement of B lymphocytes in the acquired immunodeficiency syndrome (AIDS), we used an enzyme-linked immunoassay (ELISA) to determine the levels of IgM, IgG and IgA rheumatoid factors (RF) in 16 patients suffering from full-blown AIDS and 32 patients with AIDS-related complex (ARC), in the clinical form of lymphoadenopathy syndrome (LAS), compared with 40 healthy, young heterosexual subjects. Both AIDS and ARC patients showed a greater incidence of high IgM RF levels, with mean values significantly higher than controls, but with no differences between the two pathological groups. IgG RF behaviour was similar in the two patient populations and the healthy subjects. IgA RF were significantly raised in AIDS and ARC. Further information on RF was obtained by determination of the immunoglobulin levels of the respective isotypes in the same patients. Mean IgG levels were above normal in AIDS and ARC patients, but the latter group showed a higher incidence of increased values and higher mean levels. The IgA isotype was significantly increased mainly in AIDS patients. The behaviour of IgM was virtually the same in the three groups studied. A difference between AIDS and ARC patients was established by the detection of circulating immune-complexes (IC) by the C1q-binding and CIC-conglutinin assays. IC were significantly high, by both methods, only in the ARC group, but normal or very low in AIDS. These overall findings suggest once again the impairment of B cell function in AIDS, with prevalent hyperactivation in ARC and exhaustion in full-blown AIDS, and apparent preservation, in the latter group, of the antibody responses which are more closely related to the activity of subsets of T helper cells. PMID:3608224

  18. IgM AUTOANTIBODIES TO DNA IN BLOOD SERUM OF THE PATIENTS WITH HEMORRHAGIC FEVER WITH RENAL SYNDROME

    Directory of Open Access Journals (Sweden)

    D. G. Ishmukhametova

    2010-01-01

    Full Text Available Levels of IgM autoantibodies (AAbs to native (double-stranded and denaturated (single-stranded DNA were studied in blood serum of sixty patients with hemorrhagic fever with renal syndrome (HFRS and twenty-five healthy persons, using an ELISA technique. The median levels of IgM AAbs to double-stranded DNA in blood serum of healthy persons and HFRS patients corresponded to 0.41 and 0.53 arbitrary units, respectively. Thus, the difference between the samples from HFRS and healthy persons proved to be non-significant. The median level of IgM AAbs to single-stranded DNA in blood sera of HFRS patients (0.71 arbitrary units did significantly exceed serum values of healthy persons (0.57 arbitrary units. A probable involvement of IgM AAbs into regulation of IgG AAbs' production during virus-induced activation of autoimmune events in HFRS patients is discussed.

  19. Neuropathy and IgM M-proteins - Prognostic value of antibodies to MAG, SGPG, and sulfatide

    NARCIS (Netherlands)

    Eurelings, M; Moons, KGM; Notermans, NC; Sasker, LD; De Jager, AEJ; Wintzen, AR; Wokke, JHJ; Van den Berg, LH

    2001-01-01

    Background: In polyneuropathy associated with immunoglobulin M (IgM) monoclonal gammopathy, antibodies to myelin-associated glycoprotein (MAG), sulfoglucuronyl paragloboside (SGPG), and sulfatide have been associated with specific clinical and electrophysiologic features. However, it is not known wh

  20. Development and Characterization of Monoclonal Antibodies to Yellow Fever Virus and Application in Antigen Detection and IgM Capture Enzyme-Linked Immunosorbent Assay.

    Science.gov (United States)

    Adungo, Ferdinard; Yu, Fuxun; Kamau, David; Inoue, Shingo; Hayasaka, Daisuke; Posadas-Herrera, Guillermo; Sang, Rosemary; Mwau, Matilu; Morita, Kouichi

    2016-08-01

    Yellow fever (YF) is an acute hemorrhagic viral infection transmitted by mosquitoes in Africa and South America. The major challenge in YF disease detection and confirmation of outbreaks in Africa is the limited availability of reference laboratories and the persistent lack of access to diagnostic tests. We used wild-type YF virus sequences to generate recombinant envelope protein in an Escherichia coli expression system. Both the recombinant protein and sucrose gradient-purified YF vaccine virus 17D (YF-17D) were used to immunize BALB/c mice to generate monoclonal antibodies (MAbs). Eight MAbs were established and systematically characterized by indirect enzyme-linked immunosorbent assay (ELISA), Western blot analysis, and immunofluorescence assay (IFA). The established MAbs showed strong reactivity with wild-type YF virus and recombinant protein with no detectable cross-reactivity to dengue virus or Japanese encephalitis virus. Epitope mapping showed strong binding of three MAbs to amino acid positions 1 to 51, while two MAbs mapped to amino acid positions 52 to 135 of the envelope protein. The remaining three MAbs did not show reactivity to envelope fragments. The established MAbs exert no neutralization against wild-type YF and 17D viruses (titer of <10 for both strains). The applicability of MAbs 8H3 and 3F4 was further evaluated using IgM capture ELISA. A total of 49 serum samples were analyzed, among which 12 positive patient and vaccinee samples were correctly identified. Using serum samples that were 2-fold serially diluted, the IgM capture ELISA was able to detect all YF-positive samples. Furthermore, MAb-based antigen detection ELISA enabled the detection of virus in culture supernatants containing titers of about 1,000 focus-forming units.

  1. When neutral turns significant: brain dynamics of rapidly formed associations between neutral stimuli and emotional contexts.

    Science.gov (United States)

    Ventura-Bort, Carlos; Löw, Andreas; Wendt, Julia; Dolcos, Florin; Hamm, Alfons O; Weymar, Mathias

    2016-09-01

    The ability to associate neutral stimuli with motivationally relevant outcomes is an important survival strategy. In this study, we used event-related potentials (ERPs) to investigate brain dynamics of associative emotional learning when participants were confronted with multiple heterogeneous information. Participants viewed 144 different objects in the context of 144 different emotional and neutral background scenes. During each trial, neutral objects were shown in isolation and then paired with the background scene. All pairings were presented twice to compare ERPs in response to neutral objects before and after single association. After single pairing, neutral objects previously encoded in the context of emotional scenes evoked a larger P100 over occipital electrodes compared to objects that were previously paired with neutral scenes. Likewise, larger late positive potentials (LPPs) were observed over parieto-occipital electrodes (450-750 ms) for objects previously associated with emotional relative to neutral contexts. The LPP - but not P100 - enhancement was also related to subjective object/context binding. Taken together, our ERP data provide evidence for fast emotional associative learning, as reflected by heightened perceptual and sustained elaborative processing for neutral information previously encountered in emotional contexts. These findings could assist in understanding binding mechanisms in stress and anxiety, as well as in addiction and eating-related disorders. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  2. Bleach Neutralizes Mold Allergens

    Science.gov (United States)

    Science Teacher, 2005

    2005-01-01

    Researchers at National Jewish Medical and Research Center have demonstrated that dilute bleach not only kills common household mold, but may also neutralize the mold allergens that cause most mold-related health complaints. The study, published in the Journal of Allergy and Clinical Immunology, is the first to test the effect on allergic…

  3. CO2-Neutral Fuels

    NARCIS (Netherlands)

    Goede, A.; van de Sanden, M. C. M.

    2016-01-01

    Mimicking the biogeochemical cycle of System Earth, synthetic hydrocarbon fuels are produced from recycled CO2 and H2O powered by renewable energy. Recapturing CO2 after use closes the carbon cycle, rendering the fuel cycle CO2 neutral. Non-equilibrium molecular CO2 vibrations are key to high energy

  4. CO2-Neutral Fuels

    Science.gov (United States)

    Goede, Adelbert; van de Sanden, Richard

    2016-06-01

    Mimicking the biogeochemical cycle of System Earth, synthetic hydrocarbon fuels are produced from recycled CO2 and H2O powered by renewable energy. Recapturing CO2 after use closes the carbon cycle, rendering the fuel cycle CO2 neutral. Non-equilibrium molecular CO2 vibrations are key to high energy efficiency.

  5. CO2-Neutral Fuels

    NARCIS (Netherlands)

    Goede, A.; van de Sanden, M. C. M.

    2016-01-01

    Mimicking the biogeochemical cycle of System Earth, synthetic hydrocarbon fuels are produced from recycled CO2 and H2O powered by renewable energy. Recapturing CO2 after use closes the carbon cycle, rendering the fuel cycle CO2 neutral. Non-equilibrium molecular CO2 vibrations are key to high energy

  6. Pathogenic relevance of IgG and IgM antibodies against desmoglein 3 in blister formation in pemphigus vulgaris.

    Science.gov (United States)

    Tsunoda, Kazuyuki; Ota, Takayuki; Saito, Masataka; Hata, Tsuyoshi; Shimizu, Atsushi; Ishiko, Akira; Yamada, Taketo; Nakagawa, Taneaki; Kowalczyk, Andrew P; Amagai, Masayuki

    2011-08-01

    Pemphigus vulgaris is an autoimmune disease caused by IgG antibodies against desmoglein 3 (Dsg3). Previously, we isolated a pathogenic mAb against Dsg3, AK23 IgG, which induces a pemphigus vulgaris-like phenotype characterized by blister formation. In the present study, we generated a transgenic mouse expressing AK23 IgM to examine B-cell tolerance and the pathogenic role of IgM. Autoreactive transgenic B cells were found in the spleen and lymph nodes, whereas anti-Dsg3 AK23 IgM was detected in the cardiovascular circulation. The transgenic mice did not develop an obvious pemphigus vulgaris phenotype, however, even though an excess of AK23 IgM was passively transferred to neonatal mice. Similarly, when hybridoma cells producing AK23 IgM were inoculated into adult mice, no blistering was observed. Immunoelectron microscopy revealed IgM binding at the edges of desmosomes or interdesmosomal cell membranes, but not in the desmosome core, where AK23 IgG binding has been frequently detected. Furthermore, in an in vitro dissociation assay using cultured keratinocytes, AK23 IgG and AK23 IgM F(ab')(2) fragments, but not AK23 IgM, induced fragmentation of epidermal sheets. Together, these observations indicate that antibodies must gain access to Dsg3 integrated within desmosomes to induce the loss of keratinocyte cell-cell adhesion. These findings provide an important framework for improved understanding of B-cell tolerance and the pathophysiology of blister formation in pemphigus. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  7. IgM antibodies against phenolic glycolipid I from Mycobacterium leprae in leprosy sera: relationship to bacterial index and erythema nodosum leprosum.

    Science.gov (United States)

    Schwerer, B; Meeker, H C; Sersen, G; Levis, W R

    1984-01-01

    Serum IgM antibodies against Mycobacterium leprae-derived phenolic glycolipid I (PG) were determined in 121 leprosy patients, in contacts and controls by an enzyme-linked immunosorbent assay technique. Anti-PG IgM levels correlated with disease classification, increasing from the tuberculoid towards the lepromatous pole of the disease spectrum. There was a linear correlation between serum IgM PG-antibody levels and bacillary index (BI), a measure of bacterial load. Elevated anti-PG IgM in bacillary negative patients was usually indicative of active disease, undetected by BI. We conclude that anti-PG IgM levels are valuable for monitoring the degree of disease activity. Serum anti-PG IgM levels were significantly lower in patients with erythema nodosum leprosum (ENL) as compared to those without ENL, suggesting that IgM PG-antibodies are also involved in the pathogenesis of ENL.

  8. Neutralizing Antibody Responses to Antigenically Drifted Influenza A(H3N2) Viruses among Children and Adolescents following 2014-2015 Inactivated and Live Attenuated Influenza Vaccination

    Science.gov (United States)

    Martin, Judith M.; Gross, F. Liaini; Jefferson, Stacie; Cole, Kelly Stefano; Archibald, Crystal Ann; Nowalk, Mary Patricia; Susick, Michael; Moehling, Krissy; Spencer, Sarah; Chung, Jessie R.; Flannery, Brendan; Zimmerman, Richard K.

    2016-01-01

    Human influenza A(H3N2) viruses that predominated during the moderately severe 2014-2015 influenza season differed antigenically from the vaccine component, resulting in reduced vaccine effectiveness (VE). To examine antibody responses to 2014-2015 inactivated influenza vaccine (IIV) and live-attenuated influenza vaccine (LAIV) among children and adolescents, we collected sera before and after vaccination from 150 children aged 3 to 17 years enrolled at health care facilities. Hemagglutination inhibition (HI) assays were used to assess the antibody responses to vaccine strains. We evaluated cross-reactive antibody responses against two representative A(H3N2) viruses that had antigenically drifted from the A(H3N2) vaccine component using microneutralization (MN) assays. Postvaccination antibody titers to drifted A(H3N2) viruses were higher following receipt of IIV (MN geometric mean titers [GMTs], 63 to 68; 38 to 45% achieved seroconversion) versus LAIV (MN GMT, 22; only 3 to 5% achieved seroconversion). In 9- to 17-year-olds, the highest MN titers were observed among IIV-vaccinated individuals who had received LAIV in the previous season. Among all IIV recipients aged 3 to 17 years, the strongest predictor of antibody responses to the drifted viruses was the prevaccination titers to the vaccine strain. The results of our study suggest that in an antigenically drifted influenza season, vaccination still induced cross-reactive antibody responses to drifted circulating A(H3N2) viruses, although higher antibody titers may be required for protection. Antibody responses to drifted A(H3N2) viruses following vaccination were influenced by multiple factors, including vaccine type and preexisting immunity from prior exposure. PMID:27558294

  9. Long-term response of surface water acid neutralizing capacity in a central Appalachian (USA) river basin to declining acid deposition

    Science.gov (United States)

    Kline, Kathleen M.; Eshleman, Keith N.; Garlitz, James E.; U'Ren, Sarah H.

    2016-12-01

    Long-term changes in acid-base chemistry resulting from declining regional acid deposition were examined using data from repeating synoptic surveys conducted within the 275 km2 Upper Savage River Watershed (USRW) in western Maryland (USA); a randomly-selected set of 40 stream reaches was sampled 36 times between 1999 and 2014 to: (1) repeatedly characterize the acid-base status of the entire river basin; (2) determine whether an extensive network of streams of varying order has shown signs of recovery in acid neutralizing capacity (ANC); and (3) understand the key factors controlling the rate of ANC recovery across the river network. Several non-parametric analyses of trends (i.e., Mann Kendall Trend: MKT tests; and Regional Kendall Trend: RKT) in streamwater acid-base chemistry suggest that USRW has significantly responded to declining acid deposition during the study period; the two most robust, statistically significant trends were decreasing surface water SO42- (∼1.5 μeq L-1 yr-1) and NO3- (∼1 μeq L-1 yr-1) concentrations-consistent with observed downward trends in regional wet S and N deposition. Basin-wide decreasing trends in K+, Mg2+, and Ca2+ were also observed, while Na+ concentrations increased. Significant ANC recovery was observed in 10-20% of USRW stream reaches (depending on the p level used), but the magnitude of the trend relative to natural variability was apparently insufficient to allow detection of a basin-wide ANC trend using the RKT test. Watershed factors, such as forest disturbances and increased application of road deicing salts, appeared to contribute to substantial variability in concentrations of NO3- and Na+ in streams across the basin, but these factors did not affect our overall interpretation of the results as a systematic recovery of USRW from regional acidification. Methodologically, RKT appears to be a robust method for identifying basin-wide trends using synoptic data, but MKT results for individual systems should be

  10. Immunopotentiality of Ayurvedic polyherbal formulations “Saribadi” and “Anantamul Salsa” with augmentation of IgM production and lymphocytes proliferation:A preliminary study

    Institute of Scientific and Technical Information of China (English)

    Md Moklesur Rahman Sarker; Long Chiau Ming; Md Zaidul Islam Sarker; M Shahabuddin Kabir Choudhuri

    2016-01-01

    Objective: To assess the immunopotentiality of Ayurvedic polyherbal preparations,“Saribadi”and“Anantamul Salsa”. Methods: Freshly prepared BALB/c mice splenocytes were cultured with“Saribadi”or“Anantamul Salsa” treatment [doses of 0.25%, 0.50%, 0.75%, 1.00%, 1.50%, 2.00%, 3.00%and 4.00%(v/v)] at 37 ? C for 5 days. The immunoglobulin M (IgM) production and lymphocytes proliferation were determined by ELISA and MTT methods, respectively. Endotoxin contamination was assessed by treating the preparations with polymyxin B. Results: The doses of“Saribadi”[0.25%, 0.50%, 0.75%and 1.00%(v/v)] significantly increased IgM productions (0.966, 0.728, 0.695 and 0.615 mg/mL vs. control 0.265 mg/mL) and lymphocytes proliferation [absorbance 0.311, 0.394, 0.372 and 0.334 optical density (OD) vs. control 0.162 OD]. Similarly, the doses of“Anantamul Salsa”[0.50%, 0.75%, 1.00%and 1.50%(v/v)] promoted IgM productions (0.933, 0.919, 0.917 and 0.892 mg/mL vs. control 0.502 mg/mL) and the doses of “Anantamul Salsa” [0.50%, 0.75%, 1.00%, 1.50%, 2.00%, and 3.00%(v/v)] stimulated lymphocytes proliferation (absorbance 0.395, 0.326, 0.440, 0.398, 0.452 and 0.355 OD vs. control 0.199 OD). The activity of“Saribadi”and“Anantamul Salsa”was not retarded by the treatment of preparations with polymyxin B. Conclusions: Immunomodulatory activity of “Saribadi” and “Anantamul Salsa” was unveiled for the first time.“Saribadi”and“Anantamul Salsa”possess immunostimulating potential acting through the induction of lymphocyte proliferation and IgM production. These preparations may be useful in strengthening immune responses. However, further cellular and in vivo studies are required.

  11. [Standardization of ELISA IgM and IgA for immunodiagnosis of human trichinosis].

    Science.gov (United States)

    Contreras, M C; Acevedo, E; Aguilera, S; Sandoval, L; Salinas, P

    1999-01-01

    An ELISA test for trichinosis using as antigen a larvae soluble fraction from Trichinella spiralis was carried out for the detection of IgM and IgA specific antibodies in 45 serum samples from patients confirmed or suspected to have trichinosis by strong clinical and epidemiological evidences. All the patients had positive serology detected by precipitin test, bentonite floculation test, indirect hemagglutination test and ELISA IgG test. The cut-off value was determined using two criteria. Criterion A was determined in each plate, using three positive controls and two negative ones; the average of the negative controls and the weakest positive control, multiplied by a 1.2 factor was, considered the cut-off value. Criterion B was determined using the average plus three standard deviations from 64 apparently healthy persons serum samples. In both cases, three serum dilutions (1:10, 1:100 and 1:500) were used. The sensitivity of ELISA IgM was 100.0, 93.3 and 82.2% using serum dilutions of 1:10, 1:100 and 1:500 respectively (criterion A) and 100.0, 97.8 and 95.6% for the same dilutions (criterion B), whereas the values for ELISA IgA were: 100.0, 91.1 and 86.7% (criterion A) and 100.0, 100.0 and 91.1% (criterion B). In order to find out the specificity of ELISA IgM and ELISA IgA, additional 118 serum samples from individuals with other parasitoses, such as cysticercosis (18) hydatidosis (39), fascioliasis (12), toxocariasis (30), Chagas' disease (12) and individuals with non-specific eosinophilia (7), were also tested. ELISA IgM presented a specificity of 92.3, 93.4 and 97.3% (criterion A) and 96.2, 97.8 and 97.8% (criterion B) whereas the results for ELISA IgA were 97.8, 98.9 and 99.4% (criterion A) and 98.4% for the 1:10 and 1:100 dilutions and 100.0% for the 1:500 dilution (criterion B). The positive predictive values of ELISA IgM were 76.3, 77.8 and 88.1% (criterion A) and 86.5, 91.7 and 91.5% (criterion B) whereas the negative ones were 100.0, 98.3 and 95

  12. Ultracold Neutral Plasmas

    CERN Document Server

    Killian, T C; Gupta, P; Laha, S; Martinez, Y N; Mickelson, P G; Nagel, S B; Saenz, A D; Simien, C E; Killian, Thomas C.

    2005-01-01

    Ultracold neutral plasmas are formed by photoionizing laser-cooled atoms near the ionization threshold. Through the application of atomic physics techniques and diagnostics, these experiments stretch the boundaries of traditional neutral plasma physics. The electron temperature in these plasmas ranges from 1-1000 K and the ion temperature is around 1 K. The density can approach $10^{11}$ cm$^{-3}$. Fundamental interest stems from the possibility of creating strongly-coupled plasmas, but recombination, collective modes, and thermalization in these systems have also been studied. Optical absorption images of a strontium plasma, using the Sr$^+$ ${^2S_{1/2}} -> {^2P_{1/2}}$ transition at 422 nm, depict the density profile of the plasma, and probe kinetics on a 50 ns time-scale. The Doppler-broadened ion absorption spectrum measures the ion velocity distribution, which gives an accurate measure of the ion dynamics in the first microsecond after photoionization.

  13. Gargamelle: neutral current event

    CERN Multimedia

    1973-01-01

    This event shows real tracks of particles from the 1200 litre Gargamelle bubble chamber that ran on the PS from 1970 to 1976 and on the SPS from 1976 to 1979. In this image a neutrino passes close to a nucleon and reemerges as a neutrino. Such events are called neutral curent, as they are mediated by the Z0 boson which has no electric charge.

  14. Neutral atom traps.

    Energy Technology Data Exchange (ETDEWEB)

    Pack, Michael Vern

    2008-12-01

    This report describes progress in designing a neutral atom trap capable of trapping sub millikelvin atom in a magnetic trap and shuttling the atoms across the atom chip from a collection area to an optical cavity. The numerical simulation and atom chip design are discussed. Also, discussed are preliminary calculations of quantum noise sources in Kerr nonlinear optics measurements based on electromagnetically induced transparency. These types of measurements may be important for quantum nondemolition measurements at the few photon limit.

  15. Probing the IGM/Galaxy Connection V: On the Origin of Lya and OVI Absorption at z<0.2

    CERN Document Server

    Prochaska, J Xavier; Chen, H -W; Mulchaey, J S; Cooksey, K L

    2011-01-01

    We analyze the association of galaxies to Lya and OVI absorption, the most commonly detected transitions in the low-z intergalactic medium (IGM), in the fields of 14 quasars with z_em = 0.06-0.57. Confirming previous studies, we observe a high covering fraction for Lya absorption to impact parameter rho = 300kpc: 33/37 of our L>0.01L* galaxies show Lya equivalent width W_Lya>50mA. Galaxies of all luminosity L>0.01L* and spectral type are surrounded by a diffuse and ionized circumgalactic medium (CGM), whose baryonic mass is estimated at ~10^(10.5 +/- 0.3) Msun for a constant N_H. The virialized halos and extended CGM of present-day galaxies are responsible for most strong Lya absorbers (W_Lya > 300mA) but cannot reproduce the majority of observed lines in the Lya forest. We conclude that the majority of Lya absorption with W_Lya=30-300mA occurs in the cosmic web predicted by cosmological simulations and estimate a characteristic width for these filaments of ~400kpc. Regarding OVI, we observe a near unity cove...

  16. Association between IgM anti-herpes simplex virus and plasma amyloid-beta levels.

    Directory of Open Access Journals (Sweden)

    Catherine Féart

    Full Text Available OBJECTIVE: Herpes simplex virus (HSV reactivation has been identified as a possible risk factor for Alzheimer's disease (AD and plasma amyloid-beta (Aβ levels might be considered as possible biomarkers of the risk of AD. The aim of our study was to investigate the association between anti-HSV antibodies and plasma Aβ levels. METHODS: The study sample consisted of 1222 subjects (73.9 y in mean from the Three-City cohort. IgM and IgG anti-HSV antibodies were quantified using an ELISA kit, and plasma levels of Aβ(1-40 and Aβ(1-42 were measured using an xMAP-based assay technology. Cross-sectional analyses of the associations between anti-HSV antibodies and plasma Aβ levels were performed by multi-linear regression. RESULTS: After adjustment for study center, age, sex, education, and apolipoprotein E-e4 polymorphism, plasma Aβ(1-42 and Aβ(1-40 levels were specifically inversely associated with anti-HSV IgM levels (β = -20.7, P=0.001 and β = -92.4, P=0.007, respectively. In a sub-sample with information on CLU- and CR1-linked SNPs genotyping (n=754, additional adjustment for CR1 or CLU markers did not modify these associations (adjustment for CR1 rs6656401, β = -25.6, P=0.002 for Aβ(1-42 and β = -132.7, P=0.002 for Aβ(1-40; adjustment for CLU rs2279590, β = -25.6, P=0.002 for Aβ(1-42 and β = -134.8, P=0.002 for Aβ(1-40. No association between the plasma Aβ(1-42-to-Aβ(1-40 ratio and anti-HSV IgM or IgG were evidenced. CONCLUSION: High anti-HSV IgM levels, markers of HSV reactivation, are associated with lower plasma Aβ(1-40 and Aβ(1-42 levels, which suggest a possible involvement of the virus in the alterations of the APP processing and potentially in the pathogenesis of AD in human.

  17. Selective IgM deficiency in an adult presenting with Streptococcus pneumoniae septic arthritis.

    Science.gov (United States)

    Phuphuakrat, Angsana; Ngamjanyaporn, Pintip; Nantiruj, Kanokrat; Luangwedchakarn, Voravich; Malathum, Kumthorn

    2016-02-01

    Septic arthritis caused by Streptococcus pneumoniae is uncommon. Most of the patients who have invasive pneumococcal infection have underlying diseases associated with impaired immune function. We report a case of polyarticular pneumococcal septic arthritis in a previously healthy adult as the first manifestation of selective immunoglobulin (Ig)M deficiency. The patient had no evidence of autoimmune disease or malignancy. Serum IgG, IgA, and complement levels were normal. Numbers of lymphocyte subsets were in normal range except that of CD4+ cells, which was slightly low. Invasive pneumococcal disease in a healthy adult should lead to further investigation for underlying diseases including primary immunodeficiencies.

  18. Diagnostic utility of IgG and IgM immunohistochemistry in autoimmune liver disease

    Institute of Scientific and Technical Information of China (English)

    Roger; Klein; Moreira; Frank; Revetta; Elizabeth; Koehler; Mary; Kay; Washington

    2010-01-01

    AIM:To assess the role of IgM and IgG immunohistochemistry(IHC) in the evaluation of autoimmune liver conditions-autoimmune hepatitis(AIH),primary biliary cirrhosis(PBC),and primary sclerosing cholangitis(PSC).METHODS:Forty one biopsies from untreated patients diagnosed with autoimmune liver disease(AIH,n = 20;PBC,n = 13;PSC,n = 8) and fourteen biopsies of patients with chronic hepatitis C were selected.IgM and IgG-positive plasma cells were counted in each sample.RESULTS:A predominance of IgG-positive plas...

  19. Destructive arthritis in a patient with chikungunya virus infection with persistent specific IgM antibodies

    Directory of Open Access Journals (Sweden)

    Receveur Marie-Catherine

    2009-12-01

    Full Text Available Abstract Background Chikungunya fever is an emerging arboviral disease characterized by an algo-eruptive syndrome, inflammatory polyarthralgias, or tenosynovitis that can last for months to years. Up to now, the pathophysiology of the chronic stage is poorly understood. Case presentation We report the first case of CHIKV infection with chronic associated rheumatism in a patient who developed progressive erosive arthritis with expression of inflammatory mediators and persistence of specific IgM antibodies over 24 months following infection. Conclusions Understanding the specific features of chikungunya virus as well as how the virus interacts with its host are essential for the prevention, treatment or cure of chikungunya disease.

  20. Lectin-like domain of thrombomodulin binds to its specific ligand Lewis Y antigen and neutralizes lipopolysaccharide-induced inflammatory response

    Science.gov (United States)

    Shi, Chung-Sheng; Hsiao, Shi-Ming; Kao, Yuan-Chung; Kuo, Kuan-Lin; Ma, Chih-Yuan; Kuo, Cheng-Hsiang; Chang, Bi-Ing; Chang, Chuan-Fa; Lin, Chun-Hung; Wong, Chi-Huey

    2008-01-01

    Thrombomodulin (TM), a widely expressing glycoprotein originally identified in vascular endothelium, is an important cofactor in the protein C anticoagulant system. TM appears to exhibit anti-inflammatory ability through both protein C–dependent and –independent pathways. We presently have demonstrated that recombinant N-terminal lectinlike domain of TM (rTMD1) functions as a protective agent against sepsis caused by Gram-negative bacterial infections. rTMD1 caused agglutination of Escherichia coli and Klebsiella pneumoniae and enhanced the macrophage phagocytosis of these Gram-negative bacteria. Moreover, rTMD1 bound to the Klebsiella pneumoniae and lipopolysaccharide (LPS) by specifically interacting with Lewis Y antigen. rTMD1 inhibited LPS-induced inflammatory mediator production via interference with CD14 and LPS binding. Furthermore, rTMD1 modulated LPS-induced mitogen-activated protein kinase and nuclear factor-κB signaling pathway activations and inducible nitric oxide synthase expression in macrophages. Administration of rTMD1 protected the host by suppressing inflammatory responses induced by LPS and Gram-negative bacteria, and enhanced LPS and bacterial clearance in sepsis. Thus, rTMD1 can be used to defend against bacterial infection and inhibit LPS-induced inflammatory responses, suggesting that rTMD1 may be valuable in the treatment of severe inflammation in sepsis, especially in Gram-negative bacterial infections. PMID:18711002

  1. The validity of the criteria for primary infection of Chlamydophila pneumoniae in children by measuring ELISA IgM antibodies.

    Science.gov (United States)

    Kamata, Ayako; Obinata, Kaoru; Niizuma, Takahiro; Kinoshita, Keiji; Shimizu, Toshiaki

    2012-06-01

    As IgM antibody measurement by enzyme-linked immunosorbent assay (ELISA) has become possible for the serological diagnosis of Chlamydophila pneumoniae (C. pn) infection, the HITAZYME-ELISA method has become widely employed in Japan. However, in children, when the diagnostic criterion of primary infection is set at ID ≥1.1, the positive rate is higher than expected, and the potential for inaccurate reflection of the prevalence has been raised. In this study, we performed ROC analysis involving 136 pediatric patients with acute airway symptoms (0-14 years of age), considering a 32-fold or higher micro-immunofluorescence IgM antibody titer against C. pn as positive. Setting the cut-off value for ELISA C. pn IgM antibody ID at 2.0, the specificity was 100%, with no false positivity. The maximum (sensitivity + specificity)/2 was obtained when the cut-off value was set at 1.5. Therefore, IgM ID ≥2.0 was regarded as definitely positive and an IgM ID between 1.5 and 2.0 was regarded as indeterminate as diagnostic criteria for the primary infection. When the prevalence was investigated in 3,108 children (0-15 years of age) with airway symptoms based on these criteria, 542 cases (17.4%) were positive, and the median duration of IgM antibody positivity was five months. Long-term positivity (ten cases) for more than 12 months and recurrent positivity (eight cases) were also observed, but it may be appropriate to set a new criterion of IgM antibody ID ≥2.0 for the diagnosis of primary Chlamydophila pneumoniae infection in children.

  2. Broadly neutralizing antibodies targeted to mucin-type carbohydrate epitopes of human immunodeficiency virus

    DEFF Research Database (Denmark)

    Hansen, J E; Nielsen, C; Arendrup, M;

    1991-01-01

    . This inhibition was found in infection of both lymphocytic cells and monocytoid cells. Viruses tested included six HIV-1 and five HIV-2 isolates propagated in different cells, as well as infectious plasma from AIDS patients. The antiviral effect of anti-Tn MAbs occurred by specific binding of the MAb to the virus......The cancer-related mucin-type carbohydrate neoantigen Tn was found on gp160 and gp120 of human immunodeficiency virus (HIV). Immunoglobulin G (IgG) and IgM monoclonal antibodies (MAbs) against Tn neutralized infection with cell-free virus and blocked fusion between HIV-infected and uninfected cells...

  3. Comparison of humoral immune response, neutralization capacity of anticrotalic serum in young ovines, clinical and weight evaluation between animals inoculated with Crotalus durissus terrificus venom, natural or Cobalt-60-irradiated

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira Junior, R.S. E-mail: rseabra@cevap.org.br

    2005-07-01

    The Elisa technique was used to evaluate and compare the humoral immune response of young ovine to anticrotalic serum production. During serum production, the clinical and weight evaluation of the animals was performed. The parameters utilized were complete blood count, and dosage of urea, creatinine, aspartate aminotransferase, total proteins, albumin and globulin. The animals weight was verified fortnightly during the experiment. The neutralization capacity of the serum produced from the snake Crotalus durissus terrificus natural (NV) and Cobalt-60-irradiated venom (IrV) was evaluated by in vitro challenges. One group of six animals received natural venom, the second group received irradiated venom, and the third was the control group. The animals received six immunizations during 84 days with an interval of 14 days. There was a significant difference (p<5%) in the ELISA test for the profile of the antibodies produced by the experimental groups (NVneutralization capacity of the serum produced from the IrV was fivefold higher when compared to the serum produced with NV. The clinical and weight evaluation showed that the o vines in post-weaning phase did not have their physiological profiles altered, and showed an excellent increase in weight during the experimental period. These results indicate a new perspective for the utilization of o vines, aiming the commercial production of anticrotalic serum, which may be applied in the treatment of human and animal envenomation. The cost for its production may be reduced by the posterior utilization of hyperimmunized ovine in human feeding. (author)

  4. Cold-induced precipitation of a monoclonal IgM: a negative activation enthalpy reaction.

    Science.gov (United States)

    Meliga, Stefano C; Farrugia, William; Ramsland, Paul A; Falconer, Robert J

    2013-01-17

    Cold-induced precipitation of a monoclonal IgM cryoglobulin isolated from a patient with Waldenström's macroglobulinemia was observed to have a negative activation enthalpy. The rate of the reaction increased, as the temperature decreased. Differential scanning calorimetry of the monoclonal IgM showed precipitation as an inverted peak during a downward temperature scan. The transition temperature was between 14 and 15 °C and was possibly concentration dependent. At temperatures below the transition the precipitation was best described by second-order kinetics. The difference in change in enthalpy between precipitation and disassociation suggests that cold-induced precipitation had a fast precipitation stage followed by a slower consolidation reaction. Negligible curvature of the Eyring plot suggested the precipitation reaction was dominated by van der Waal forces and hydrogen bonding. Conversely, during an upward temperature scan, disassociation was observed as a positive enthalpy peak. This reaction had two stages, a reaction undoing consolidation followed by heat-induced disassociation that had first-order kinetics.

  5. Retrospective analysis of dengue specific IgM reactive serum samples

    Directory of Open Access Journals (Sweden)

    Nemai Bhattacharya

    2013-04-01

    Full Text Available Objective: To conduct a retrospective analysis of dengue cases in Kolkata, on the basis of presence of anti-dengue IgM in their sera and presence or absence of anti-dengue IgG and dengue specific Non structural 1 (NS1 antigen in each of the serum sample. Methods: Sample was tested quantitatively employing ELISA technique, using Biorad test kits, with a view to get a more comprehensive picture of dengue in an urban endemic area and also to evaluate individual cases. Results: This reconstructed study revealed that of those 91 dengue cases, 70.3% (64 and 29.7% (27 were suffering from secondary and primary dengue respectively, showing that number of secondary dengue cases were much more than that of primary dengue cases with a possibility of emergence of DHF. A small proportion of cases 18.7% (17 were reactive for NS1. The duration of fever in NS1 antigen positive cases varied between 5 and 7 days. Of 17 NS1 reactive cases, 10 (10.9% and 7 (7.7% were suffering from secondary and primary dengue respectively. Conclusions: Early detection of primary and secondary dengue cases would be facilitated by utilizing all three parameters (NS1 antigen, anti-dengue IgM and IgG helping to evaluate, monitor and treat a dengue case effectively.

  6. Mapping the low surface brightness Universe in the UV band with Lya emission from IGM filaments

    CERN Document Server

    Silva, Marta B; Zaroubi, Saleem

    2016-01-01

    A large fraction of the baryonic matter in the Universe is located in filaments in the intergalactic medium. However, the low surface brightness of these filaments has not yet allowed their direct detection except in very special regions in the circum-galactic medium (CGM). Here we simulate the intensity and spatial fluctuations in Lyman Alpha ${\\rm (Ly\\alpha)}$ emission from filaments in the intergalactic medium (IGM) and discuss the prospects for the next generation of space based instruments to detect the low surface brightness universe at UV wavelengths. Starting with a high resolution N-body simulation we obtain the dark matter density fluctuations and associate baryons with the dark matter particles assuming that they follow the same spatial distribution. The IGM thermal and ionization state is set by a model of the UV background and by the relevant cooling processes for a hydrogen and helium gas. The ${\\rm Ly\\alpha}$ emissivity is then estimated, taking into account recombination and collisional excita...

  7. Patchy He II reionization and the physical state of the IGM

    CERN Document Server

    Gleser, L; Benson, A J; Ohno, H; Sugiyama, N; Gleser, Liron; Nusser, Adi; Benson, Andrew J.; Ohno, Hiroshi; Sugiyama, Naoshi

    2004-01-01

    We present a Monte-Carlo model of He II reionization by QSOs and its effect on the thermal state of the clumpy intergalactic medium (IGM). The model assumes that patchy reionization develops as a result of the discrete distribution of QSOs. It includes various recipes for the propagation of the ionizing photons, and treats photo-heating self-consistently. The model provides the fraction of He III, the mean temperature in the IGM, and the He II mean optical depth -- all as a function of redshift. It also predicts the evolution of the local temperature versus density relation during reionization. Our findings are as follows: The fraction of He III increases gradually until it becomes close to unity at $z\\sim 2.8-3.0$. The He II mean optical depth decreases from $\\tau\\sim 10$ at $z\\geq 3.5$ to $\\tau\\leq 0.5$ at $z\\leq 2.5$. The mean temperature rises gradually between $z\\sim 4$ and $z\\sim 3$ and declines slowly at lower redshifts. The model predicts a flattening of the temperature-density relation with significa...

  8. IgM, but not IgA rheumatoid factor interferes with anti-cardiolipin and antiβ2 glycoprotein I measurements: a quantitative analysis.

    Science.gov (United States)

    Lakos, G; Teodorescu, M

    2011-05-01

    IgM rheumatoid factor (RF) is sometimes referred to as capable of causing interference in the IgM anti-cardiolipin (aCL) testing. Published guidelines are, however, inconsistent, and evidence regarding the interference is limited. Our goal was investigate IgM and IgA RF cross-reactivity and/or interference in IgM and IgA aCL and anti-β2 glycoprotein I (aβ2GPI) testing. Serum specimens with high IgM and IgA RF levels were tested for IgG, IgA and IgM aCL and aβ2GPI antibodies to examine cross-reactivity. Samples containing IgG aCL and aβ2GPI antibodies were spiked with IgM (and IgA) RF, and samples with high RF levels were spiked with IgG aCL antibodies. The mixtures were tested for IgM and IgA aCL and aβ2GPI antibodies. Specimens with high IgM and IgA RF concentrations did not test positive for IgM or IgA aCL and aβ2GPI antibodies (except one weak positive IgA aβ2GPI result), indicating the lack of cross-reactivity. In the spiked specimens, addition of IgM RF caused significant positive bias in the measurement of both aCL and aβ2GPI antibodies of IgM isotype in the presence of IgG aCL and aβ2GPI antibodies. The threshold for triggering significant interference was 318( )IU/ml for IgM RF, and 77 GPLU/ml for IgG aCL. Neither IgM, nor IgA RF, however, affected the IgA antiphospholipid (aPL) antibody testing. IgM RF can cause a false-positive IgM aCL result in the presence of IgG aCL antibodies. In studies on the prevalence and clinical significance of IgM aPL antibodies, RF interference should be considered and RF testing should be performed.

  9. Generation, characterization and in vivo biological activity of two distinct monoclonal anti-PEG IgMs

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Yosuke; Shimizu, Taro; Mima, Yu [Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima, 1-78-1, Sho-machi, Tokushima 770-8505 (Japan); Abu Lila, Amr S. [Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima, 1-78-1, Sho-machi, Tokushima 770-8505 (Japan); Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Sharqia Governorate, Zagazig 44519 (Egypt); Ishida, Tatsuhiro, E-mail: ishida@tokushima-u.ac.jp [Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima, 1-78-1, Sho-machi, Tokushima 770-8505 (Japan); Kiwada, Hiroshi [Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima, 1-78-1, Sho-machi, Tokushima 770-8505 (Japan)

    2014-05-15

    PEGylation, the attachment of polyethylene glycol (PEG) to nanocarriers and proteins, is a widely accepted approach to improving the in vivo efficacy of the non-PEGylated products. However, both PEGylated liposomes and PEGylated proteins reportedly trigger the production of specific antibodies, mainly IgM, against the PEG moiety, which possibly leads to a reduction in safety and therapeutic efficacy of the PEGylated products. In the present study, two monoclonal anti-PEG IgMs — HIK-M09 via immunization with an intravenous injection of PEGylated liposomes (SLs) and HIK-M11 via immunization with a subcutaneous administration of PEGylated ovalbumin (PEG-OVA) were successfully generated. The generated IgMs showed efficient reactivity to mPEG{sub 2000} conjugated to 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine (DSPE), PEGylated liposome (SL) and PEG-OVA. It appears that HIK-M09 recognizes ethoxy (OCH{sub 2}CH{sub 2}) repeat units along with a terminal motif of PEG, while HIK-M11 recognizes only ethoxy repeat units of PEG. Such unique properties allow HIK-M09 to bind with dense PEG. In addition, their impact on the in vivo clearance of the PEGylated products was investigated. It was found that the generated ant-PEG IgMs induced a clearance of SL as they were intravenously administered with SL. Interestingly, the HIK-M11, generated by PEG-OVA, induced the clearance of both SL and PEG-OVA, while the HIK-M09, generated by SL, induced the clearance of SL only. We here revealed that the presence of serum anti-PEG IgM and the subsequent binding of anti-PEG IgM to the PEGylated products are not necessarily related to the enhanced clearance of the products. It appears that subsequent complement activation following anti-PEG IgM binding is the most important step in dictating the in vivo fate of PEGylated products. This study may have implications for the design, development and clinical application of PEGylated products and therapeutics. - Highlights: • Two monoclonal

  10. Chemical characterization of a polar portion in the neutral fraction derived from airborne particulate extracts responsible for the embryotoxicity in the chicken embryo

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, H.

    1988-01-01

    Airborne particulate matter was collected with a high-volume air sampler between June 1984 and May 1985 on the roof top of the authors institute. The tar material extracted was separated into six fractions by liquid-liquid partition and silica gel column chromatography. These fractions were then tested for their embryotoxicities by a chicken embryo assay. A moderately polar fraction per weight and a fraction containing polycyclic aromatic hydrocarbons (PAHs) had the greatest toxicity for chicken embryos. When the polar fraction was purified by high-pressure liquid chromatography, the purified fraction was 3.7 times more toxic than the original polar fraction. To determine the responsible components for the toxicity, the purified fraction as well as the original fraction was analyzed by capillary gas chromatography and gas chromatography-mass spectrometry. The characterized components were classified into oxygenated PAHs (containing ketones, quinones, and aldehydes), nitrogen-containing PAHS, diphenyl-substituted aliphatic ketones (or diketones), and esters of aliphatic acids.

  11. Ultracold neutral plasmas

    Science.gov (United States)

    Lyon, M.; Rolston, S. L.

    2017-01-01

    By photoionizing samples of laser-cooled atoms with laser light tuned just above the ionization limit, plasmas can be created with electron and ion temperatures below 10 K. These ultracold neutral plasmas have extended the temperature bounds of plasma physics by two orders of magnitude. Table-top experiments, using many of the tools from atomic physics, allow for the study of plasma phenomena in this new regime with independent control over the density and temperature of the plasma through the excitation process. Characteristic of these systems is an inhomogeneous density profile, inherited from the density distribution of the laser-cooled neutral atom sample. Most work has dealt with unconfined plasmas in vacuum, which expand outward at velocities of order 100 m/s, governed by electron pressure, and with lifetimes of order 100 μs, limited by stray electric fields. Using detection of charged particles and optical detection techniques, a wide variety of properties and phenomena have been observed, including expansion dynamics, collective excitations in both the electrons and ions, and collisional properties. Through three-body recombination collisions, the plasmas rapidly form Rydberg atoms, and clouds of cold Rydberg atoms have been observed to spontaneously avalanche ionize to form plasmas. Of particular interest is the possibility of the formation of strongly coupled plasmas, where Coulomb forces dominate thermal motion and correlations become important. The strongest impediment to strong coupling is disorder-induced heating, a process in which Coulomb energy from an initially disordered sample is converted into thermal energy. This restricts electrons to a weakly coupled regime and leaves the ions barely within the strongly coupled regime. This review will give an overview of the field of ultracold neutral plasmas, from its inception in 1999 to current work, including efforts to increase strong coupling and effects on plasma properties due to strong coupling.

  12. Net neutrality towards a co-regulatory solution

    CERN Document Server

    Marsden, Christopher T

    2010-01-01

    In considering market developments and policy responses to some of the most heated net-neutrality debates in Europe and the United States, Net Neutrality is the first, fully comprehensive overview of the subject. This book is also unique in providing readers with a supplementary outline of recommended policy prescriptives.

  13. The Weak Neutral Current

    CERN Document Server

    Erler, Jens

    2013-01-01

    This is a review of electroweak precision physics with particular emphasis on low-energy precision measurements in the neutral current sector of the electroweak theory and includes future experimental prospects and the theoretical challenges one faces to interpret these observables. Within the minimal Standard Model they serve as determinations of the weak mixing angle which are competitive with and complementary to those obtained near the Z-resonance. In the context of new physics beyond the Standard Model these measurements are crucial to discriminate between models and to reduce the allowed parameter space within a given model. We illustrate this for the minimal supersymmetric Standard Model with or without R-parity.

  14. Mod en neutral seksualitet!

    DEFF Research Database (Denmark)

    Leer, Jonatan

    2013-01-01

    the paradigm”. This notion was presented at a series of lectures at Collège de France in 1977. Through a reading of Barthes’s autobiography, Roland Barthes par Roland Barthes (1975), the article demonstrates how Barthes in this text tries to outplay the paradigms that rules over the hegemonic understanding...... of gender and sexuality; also the fragmented text presents a vision of a sexual utopia, a neutral sexuality, that tries – like the queer theory – to go and think beyond a binary conception of gender and sexuality. Finally, it is suggested that we should start to think about a movement of “French queer...

  15. Clinical evaluation of dengue RNA, NS1, and IgM for diagnosis of dengue in Southern China.

    Science.gov (United States)

    Chen, Xinliang; Chen, Rui; Gu, Wenshen; He, Jian; Cai, Weipeng; Li, Jiajia; Duan, Chaohui; Yan, Haiyan

    2016-01-01

    In 2014, a large outbreak of dengue occurred in Guangzhou, China. This outbreak prompted us to evaluate NS1 and RNA for the early diagnosis of acute dengue infection, in addition to the combination with IgM antibody. We aimed to find the differences of three assays about dengue diagnosis. This study was an evaluation of diagnosis test. Based on WHO criteria 2009, dengue RNA, NS1, and IgM/IgG were detected from 294 patients (180 dengue patients, 114 non-dengue patients) by three diagnostic kits made in China. The χ(2) test, sensitivity, and specificity were used in statistical analysis. The ratios of dengue patients with low platelet counts (dengue patients (P Dengue NS1 was shown sensitive (93.9%) for diagnostic use. RNA had a better performance with 98.1% of sensitivity from day 1 to day 4 after illness onset. IgM performed better at day 5 or more with 74.0% of sensitivity. The diagnostic rate using a combination of RNA and IgM was 97.8% and 96.7% using NS1 and IgM. A patient with low platelet and white blood cell counts needs additional tests for dengue during an epidemic. RNA and NS1 were most valuable for early diagnosis of dengue, whereas IgM was best suited as a supplementary method for patients at day 5 or more after illness onset.

  16. Conserved natural IgM antibodies mediate innate and adaptive immunity against the opportunistic fungus Pneumocystis murina.

    Science.gov (United States)

    Rapaka, Rekha R; Ricks, David M; Alcorn, John F; Chen, Kong; Khader, Shabaana A; Zheng, Mingquan; Plevy, Scott; Bengtén, Eva; Kolls, Jay K

    2010-12-20

    Host defense against opportunistic fungi requires coordination between innate and adaptive immunity for resolution of infection. Antibodies generated in mice vaccinated with the fungus Pneumocystis prevent growth of Pneumocystis organisms within the lungs, but the mechanisms whereby antibodies enhance antifungal host defense are poorly defined. Nearly all species of fungi contain the conserved carbohydrates β-glucan and chitin within their cell walls, which may be targets of innate and adaptive immunity. In this study, we show that natural IgM antibodies targeting these fungal cell wall carbohydrates are conserved across many species, including fish and mammals. Natural antibodies bind fungal organisms and enhance host defense against Pneumocystis in early stages of infection. IgM antibodies influence recognition of fungal antigen by dendritic cells, increasing their migration to draining pulmonary lymph nodes. IgM antibodies are required for adaptive T helper type 2 (Th2) and Th17 cell differentiation and guide B cell isotype class-switch recombination during host defense against Pneumocystis. These experiments suggest a novel role for the IgM isotype in shaping the earliest steps in recognition and clearance of this fungus. We outline a mechanism whereby serum IgM, containing ancient specificities against conserved fungal antigens, bridges innate and adaptive immunity against fungal organisms.

  17. Elicitation of broadly neutralizing antibodies against HIV-1 – the germline/maturation hypothesis

    Directory of Open Access Journals (Sweden)

    Prabakaran ePonraj

    2014-08-01

    Full Text Available We have previously observed that all known broadly neutralizing antibodies (bnAbs against HIV-1 are highly divergent from their putative germline predecessors in contrast to bnAbs against henipaviruses and SARS coronavirus, which are much less divergent from their germline counterparts. We have hypothesized that because the germline antibodies are so different compared to the highly somatically mutated HIV-1 bnAbs they may not bind to the Env. This led us to the hypothesis that the immunogenicity of the highly conserved epitopes on the HIV-1 envelope glycoproteins (Envs is reduced or eliminated by their very weak or absent interactions with germline antibodies. Thus immune responses leading to elicitation of bnAbs may not be initiated and/or sustained; even if they are, the maturation pathways are so complex that prolonged periods of time may be required for elicitation of such bnAbs. In support of the hypothesis, our initial experiments showed that germline-like precursors of several bnAbs do not bind to their epitopes. Recently, a number of research groups working in the HIV vaccine field have obtained data supporting and further expanding the germline/maturation hypothesis. Vaccine immunogens that could bind putative germline antibody predecessors of known bnAbs were successfully generated. However, guiding the immune system through the exceptionally complex antibody maturation pathways in order to elicit those bnAbs remains a major challenge. Here, we summarize developments in the HIV-1 vaccine field based on the germline/maturation hypothesis including our recent data demonstrating germline-like VRC01 antibodies in a human cord blood IgM library.

  18. Is /h/ phonetically neutral?

    Science.gov (United States)

    Robb, Michael P; Chen, Yang

    2009-11-01

    Use of /h/ in the phrase, 'Say /hVC/ again' has been tacitly assumed to provide a neutral phonetic context in which to study the articulatory characteristics of speech either preceding or following /h/ articulation. Yet, assessment of the stability or neutrality of /h/ has gone untested. The current study sought to determine whether articulation of /h/ differs according to sex and language accent, as well as to examine its influence on subsequent vowel articulation. Selected acoustic features of /hVC/ were measured in 40 speakers of American English (AE) and 40 speakers of Mandarin-accented English (MAE). Results of an analysis of /h/ duration revealed no sex differences within each language group, however considerable variation was found according to accented vs unaccented English. Clear sex differences were found for the production of /h/, occurring more often among male speakers regardless of language variety. Considerable variation in production of /h/ was found between language groups. Analysis of vowel formant frequencies immediately following /h/ articulation indicated minimal coarticulatory effects for both AE and MAE speakers. The present results appear to support the suggestion that /h/ is not exclusively sex-linked and may indeed vary according to non-biological factors. In spite of these variations, /h/ articulation appears to have a negligible influence on neighbouring vowel articulation.

  19. Imatinib treatment induces CD5+ B lymphocytes and IgM natural antibodies with anti-leukemic reactivity in patients with chronic myelogenous leukemia.

    Directory of Open Access Journals (Sweden)

    Silvia Catellani

    Full Text Available Imatinib mesylate is a first line treatment of Chronic Myelogenous Leukemia and of a rare form of gastrointestinal stromal cancer, where the response to the drug is also linked to the immune system activation with production of antineoplastic cytokines. In this study, forty patients in the chronic phase of disease, treated with imatinib mesylate, were analyzed. Bone marrow aspirates were drawn at diagnosis, after 3, 6, 12, 18 months for haematological, cytofluorimetric, cytogenetic, biomolecular evaluation and cytokine measurement. Responder and non responder patients were defined according to the European LeukemiaNet recommendations. In responder patients (n = 32, the percentage of bone marrow CD20(+CD5(+sIgM(+ lymphocytes, and the plasma levels of IgM, were significantly higher, at 3 months and up to 9 months, than in non responders. These IgM reacted with O-linked sugars expressed by leukemic cells and could induce tumor cell apoptosis. In responder patients the stromal-derived factor-1 and the B-lymphocyte-activating factor of the tumor necrosis factor family significantly raised in the bone marrow after imatinib administration, together with the bone morphogenetic proteins-2 and -7. All patients with high number of CD20(+CD5(+sIgM(+ cells and high stromal-derived factor-1 and B lymphocyte activating factor levels, underwent complete cytogenetic and/or molecular remission by 12 months. We propose that CD20(+CD5(+sIgM(+ lymphocytes producing anti-carbohydrate antibodies with anti-tumor activity, might contribute to the response to imatinib treatment. As in multivariate analysis bone marrow CD20(+CD5(+sIgM(+ cells and stromal-derived factor-1 and B-lymphocyte-activating factor levels were significantly related to cytogenetical and molecular changes, they might contribute to the definition of the pharmacological response.

  20. Relativistic Pair Beams from TeV Blazars: A Source of Reprocessed GeV Emission rather than IGM Heating

    CERN Document Server

    Sironi, Lorenzo

    2013-01-01

    The interaction of TeV photons from blazars with the extragalactic background light produces a relativistic beam of electron-positron pairs streaming through the intergalactic medium (IGM). The fate of the beam energy is uncertain. By means of two- and three-dimensional particle-in-cell simulations, we study the non-linear evolution of dilute ultra-relativistic pair beams propagating through the IGM. We explore a wide range of beam Lorentz factors gamma_b>>1 and beam-to-plasma density ratios alpha 0.2 (as typically expected for blazar-induced beams), the fraction of beam energy deposited into the IGM is much smaller than ~10%. It follows that at least ~90% of the beam energy is still available to power the GeV emission produced by inverse Compton up-scattering of the Cosmic Microwave Background by the beam pairs.

  1. Severe autoimmune hemolytic anemia associated with IgM warm auto-antibodies in primary Sjögren's syndrome.

    Science.gov (United States)

    Shinoda, Koichiro; Taki, Hirofumi; Hounoki, Hiroyuki; Ogawa, Reina; Sugiyama, Eiji; Tobe, Kazuyuki

    2010-02-01

    Primary Sjögren's syndrome is an autoimmune disorder involving mainly salivary and lachrymal glands. However, many extraglandular symptoms have also been reported. Although leucocytopenia and lymphocytopenia are frequently observed in hematological disorders, autoimmune hemolytic anemia is rarely reported. We experienced a case of primary Sjögren's syndrome developing severe autoimmune hemolytic anemia. The patient's red blood cells showed spontaneous agglutination in saline at room temperature, and immunoglobulin M (IgM) was detected on the surface of red blood cells by flow cytometry, indicating that autoimmune hemolytic anemia was caused by warm reactive IgM antibodies. Immediate corticosteroid therapy resulted in a dramatic recovery. We report a first case of severe autoimmune hemolytic anemia caused by warm reactive IgM antibodies in primary Sjögren's syndrome.

  2. Cosmic Galaxy-IGM HI Relation at ${\\it{z}}\\sim 2-3$ Probed in the COSMOS/UltraVISTA $1.6$ deg$^2$ Field

    CERN Document Server

    Mukae, Shiro; Kakiichi, Koki; Suzuki, Nao; Ono, Yoshiaki; Cai, Zheng; Inoue, Akio K; Chiang, Yi-Kuan; Shibuya, Takatoshi; Matsuda, Yuichi

    2016-01-01

    We present spatial correlations of galaxies and IGM neutral hydrogen HI in the COSMOS/UltraVISTA 1.62 deg$^2$ field. Our data consist of 13415 photo-$z$ galaxies at $z\\sim2-3$ with $K_s<23.4$ and the Ly$\\alpha$ forest absorptions in the background quasar spectra selected from SDSS data with no signature of damped Ly$\\alpha$ system contamination. We estimate a galaxy overdensity $\\delta_{gal}$ in an impact parameter of 2.5 pMpc, and calculate the Ly$\\alpha$ forest fluctuations $\\delta_{\\langle F\\rangle}$ whose negative values correspond to the strong Ly$\\alpha$ forest absorptions. We identify a weak anti-correlation between $\\delta_{gal}$ and $\\delta_{\\langle F\\rangle}$ with a Spearman's rank correlation coefficient of $-0.39$ suggesting that the galaxy overdensities and the Ly$\\alpha$ forest absorptions positively correlate in space at the $\\sim90\\%$ confidence level. This positive correlation indicates that high-$z$ galaxies exist around an excess of HI gas in the Ly$\\alpha$ forest. We find four cosmic vo...

  3. Secretory IgA, IgG, and IgM immunoglobulins isolated simultaneously from colostral whey by selective thiophilic adsorption.

    Science.gov (United States)

    Hutchens, T W; Magnuson, J S; Yip, T T

    1990-03-27

    In order to evaluate the collective contribution of immunoglobulins to gastrointestinal and immune system development in newborn infants, it would be advantageous to develop a simple and rapid procedure for the selective and quantitative removal of all immunoglobulin classes from colostrum and milk. Toward this end, the major immunoglobulin classes typically present in colostrum (IgM, sIgA, and IgG) have been isolated simultaneously by selective removal from a porcine colostral whey model system using a single-step, preparative scale procedure termed thiophilic adsorption. At neutral pH, the salt-promoted thiophilic affinity of immunoglobulins for the synthetic sulfone-thioether ligands exploits a common (as yet unknown) structural feature of immunoglobulins. The adsorption and recovery procedures operate efficiently under mild buffer conditions permitting the subsequent comparative biochemical analyses of individual immunoglobulin classes for structural and functional heterogeneity. Thus, 1 liter columns of thiophilic adsorbent (T-gel) were employed to obtain pure, structurally intact immunoglobulins from 1 liter batches of porcine colostral whey. The identity and purity of the isolated immunoglobulins were determined under both structure-stabilizing ('native') conditions and denaturing conditions using high-performance size-exclusion chromatography, sucrose density gradient centrifugation, immunodiffusion techniques, SDS-polyacrylamide gradient gel electrophoresis with immunoblotting identification procedures, and two-dimensional electrophoresis. This is the first procedure known to us that allows for the simultaneous one-step isolation (under homologous conditions) of various immunoglobulins with preserved quaternary structure and apparent biological activity.

  4. The majority of human memory B cells recognizing RhD and tetanus resides in IgM+ B cells.

    Science.gov (United States)

    Della Valle, Luciana; Dohmen, Serge E; Verhagen, Onno J H M; Berkowska, Magdalena A; Vidarsson, Gestur; Ellen van der Schoot, C

    2014-08-01

    B cell memory to T cell-dependent (TD) Ags are considered to largely reside in class-switched CD27(+) cells. However, we previously observed that anti-RhD (D) Igs cloned from two donors, hyperimmunized with D(+) erythrocytes, were predominantly of the IgM isotype. We therefore analyzed in this study the phenotype and frequency of D- and tetanus toxoid-specific B cells by culturing B cells in limiting dilution upon irradiated CD40L-expressing EL4.B5 cells and testing the culture supernatant. Most Ag-specific B cells for both TD Ags were found to reside in the IgM-expressing B cells, including CD27(-) B cells, in both hyperimmunized donors and nonhyperimmunized volunteers. Only shortly after immunization a sharp increase in Ag-specific CD27(+)IgG(+) B cells was observed. Next, B cells were enriched with D(+) erythrocyte ghosts and sorted as single cells. Sequencing of IGHV, IGLV, IGKV, and BCL6 genes from these D-specific B cell clones demonstrated that both CD27(-)IgM(+) and CD27(+)IgM(+) B cells harbored somatic mutations, documenting their Ag-selected nature. Furthermore, sequencing revealed a clonal relationship between the CD27(-)IgM(+), CD27(+)IgM(+), and CD27(+)IgG(+) B cell subsets. These data strongly support the recently described multiple layers of memory B cells to TD Ags in mice, where IgM(+) B cells represent a memory reservoir which can re-enter the germinal center and ensure replenishment of class-switched memory CD27(+) B cells from Ag-experienced precursors.

  5. Skin Inqjuries Reduce Survival and Modulate Corticosterone, C-Reactive Protein, Complement Component 3, IgM, and Prostaglandin E2 after Whole-Body Reactor-Produced Mixed Field (n + γ-Photons Irradiation

    Directory of Open Access Journals (Sweden)

    Juliann G. Kiang

    2013-01-01

    Full Text Available Skin injuries such as wounds or burns following whole-body γ-irradiation (radiation combined injury (RCI increase mortality more than whole-body γ-irradiation alone. Wound-induced decreases in survival after irradiation are triggered by sustained activation of inducible nitric oxide synthase pathways, persistent alteration of cytokine homeostasis, and increased susceptibility to systemic bacterial infection. Among these factors, radiation-induced increases in interleukin-6 (IL-6 concentrations in serum were amplified by skin wound trauma. Herein, the IL-6-induced stress proteins including C-reactive protein (CRP, complement 3 (C3, immunoglobulin M (IgM, and prostaglandin E2 (PGE2 were evaluated after skin injuries given following a mixed radiation environment that might be found after a nuclear incident. In this report, mice received 3 Gy of reactor-produced mixed field (n+γ-photons radiations at 0.38 Gy/min followed by nonlethal skin wounding or burning. Both wounds and burns reduced survival and increased CRP, C3, and PGE2 in serum after radiation. Decreased IgM production along with an early rise in corticosterone followed by a subsequent decrease was noted for each RCI situation. These results suggest that RCI-induced alterations of corticosterone, CRP, C3, IgM, and PGE2 cause homeostatic imbalance and may contribute to reduced survival. Agents inhibiting these responses may prove to be therapeutic for RCI and improve related survival.

  6. Organic neutralization agents for neutralization-reionization mass spectrometry.

    Science.gov (United States)

    Zhang, M Y; McLafferty, F W

    1992-02-01

    Porter has shown that excited neutrals of specified internal energies can be prepared by neutralization of an ion beam with metal vapors of low ionization potential (IP). For specific problems in neutralization-reionization mass spectrometry, a metal with the desired IP value may not be available, or it may present experimental problems such as a high vaporization temperature, instrument contamination, or detector instability. The use of organic neutralization agents such as tetra-p-anisylethylene (IP = 6.0 eV) can minimize these problems (although cross sections for neutralization with these are a factor of 5 lower than those with metals), and can provide a much wider range of IP values. Their utility is demonstrated in the neutralization of C4H4 (+•) and CH8 (+•) ions to produce C4H4 and C4H8 of selected internal energies. However, for CH4 (+•) neutralization, the CH4 neutrals formed have a much lower internal energy than predicted, indicating that electron transfer from the neutralization agent predominantly produces its ions in excited states.

  7. A study of the association of human secretory component with IgA and IgM proteins.

    Science.gov (United States)

    Weicker, J; Underdown, B J

    1975-04-01

    Human secretory component (SC) was isolated from colostral whey, and the binding of 125I-SC to purified IgA and IgM monoclonal proteins was studied using two methods to separate free from immunoglobulin-bound 125I-SC: a) gel filtration on Sephadex G-200, and b) precipitation of 125I-SC-Ig complexes with anti-Ig antibody. Both IgA dimeric proteins and IgM pentamers bound 125I-SC with approximately one SC-binding site per mole of polymer and similar affinity. Assuming a reversible equilibrium, an apparent association constant congruent to 10-8 M-1 was calculated to govern the binding of 125I-SC to immunoglobulin polymers. The assignment of a single association constant may be an oversimplication, particularly for the case of IgA polymers, since evidence was obtained that disulfide bonds were formed in the 125I-SC-IgA complex. Despite the complexity of the reaction, binding of 125I-SC to both IgA and IgM polymers could be analyzed by standard methods of saturation analysis, and both were shown to have a similar affinity for 125I-SC. No differences were noted in the affinity of 125I-SC binding to the IgA1 and IgA2 subclasses. Binding of monomeric IgA and IgM proteins could not be measured and was at least 100-fold lower than that found for IgA and IgM polymers. Complexes of 125I-SC with IgA dimers were presumed to involve covalent bond formation, since these complexes did not dissociate in guanidine-HCl. One IgA2 trimer did not form a covalent bond since it was completely dissociated in guanidine. In contrast, 125I-SC-IgM complexes were dissociated in denaturing solvent, indicating that such complexes were held together primarily by non-covalent bonds. Experiments with (Fc)5 mu isolated by high temperature tryptic digestion of IgM showed that binding of 125I-SC was to the Fc region of IgM proteins. It was suggested that the binding of SC with similar affinity to both IgA and IgM polymers may be important in the biologic function of both these immunoglobulin classes.

  8. Detection of Thyroid Carcinoma Antigen with Quantum Dots and Monoclonal IgM Antibody (JT-95 System

    Directory of Open Access Journals (Sweden)

    Kouki Fujioka

    2010-01-01

    Full Text Available High-intensity fluorescent nanoparticles, quantum dots (QDs, have been applied to a wide range of biological studies and medical studies by taking advantage of their fluorescent properties. On the other hand, we have reported the specificity of JT-95 monoclonal IgM antibody, which recognizes the antigen of thyroid carcinomas. Here we show that the combination of QDs and JT-95 monoclonal antibody was applicable to Western blotting analysis, ELISA-like system, and fluorescent microscopic analysis of SW1736 thyroid carcinoma cell line. We have opened up the possibility that antibodies for higher specific recognition, even IgM, are applicable to the detection system with QDs.

  9. Spectroscopy of neutral radium

    Energy Technology Data Exchange (ETDEWEB)

    Mol, Aran; De, Subhadeep; Jungmann, Klaus; Wilschut, Hans; Willmann, Lorenz [KVI, University of Groningen, Groningen (Netherlands)

    2008-07-01

    The heavy alkaline earth atoms radium is uniquely sensitive towards parity and time reversal symmetry violations due to a large enhancement of an intrinsic permanent electric dipole moment of the nucleous or the electron. Furthermore, radium is sensitive to atomic parity violation and the nuclear anapole moment. To prepare such experiments spectroscopy of relevant atomic states need to be done. At a later stage we will build a neutral atom trap for radium. We have built an atomic beam of the short lived isotope {sup 225}Ra with a flux of several 10{sup 4} atoms/sec. We are preparing the laser spectroscopy using this beam setup. In the preparation for efficient laser cooling and trapping we have successfully trapped barium, which is similar in it's requirements for laser cooling. The techniques which we have developed with barium can be used to trap rare radium isotopes. We report on the progress of the experiments.

  10. Immunoglobulin M and G antibody responses to Plasmodium falciparum glutamate-rich protein

    DEFF Research Database (Denmark)

    Dziegiel, M; Rowe, P; Bennett, S;

    1993-01-01

    The aims of the present study were to describe the age-related immunoglobulin M (IgM) and IgG response to part of a 220-kDa glutamate-rich protein (GLURP) from Plasmodium falciparum and to determine possible correlations of possession of these antibodies with malaria morbidity. IgM and IgG levels...

  11. Prevalence of specific IGM due to toxoplasma, rubella, CMV and c.trachomatis infections during pregnancy

    Directory of Open Access Journals (Sweden)

    Yasodhara P

    2001-01-01

    Full Text Available One hundred and seventy five apparently normal asymptomatic pregnant women were studied prospectively and 247 women with different complications of pregnancy were screened at the time of delivery for infections like Chlamydia trachomatis, Toxoplasma, Rubella and cytomegalovirus (CMV. One hundred and forty two women with normal outcome of pregnancy served as controls. Specific IgM due to these agents were determined in the sera using commercial diagnostic kits. Results of the study showed that chlamydial infection was the most prevalent (29.8% followed by Toxoplasmosis (13.1, Rubella (6.5% and CMV (5.8%. Adverse outcome was seen among those seropositive for Chlamydia, Toxoplasmosis and Rubella. CMV showed no association with adverse outcome of pregnancy. Since Chlamydia and Toxoplasmosis are amenable to treatment with antibiotics, screening for these infections and appropriate treatment would improve outcome of pregnancy.

  12. AGN activity and IGM heating in fossil cluster RX J1416.4+2315

    CERN Document Server

    Miraghaei, H; Sengupta, C; Raychaudhury, S; Jetha, N N; Abbassi, S

    2015-01-01

    We study Active Galactic Nucleus (AGN) activity in the fossil galaxy cluster, RX J1416.4+2315. Radio observations were carried out using Giant Metrewave Radio Telescope (GMRT) at two frequencies, 1420 MHz and 610 MHz. A weak radio lobe that extends from the central nucleus is detected in 610 MHz map. Assuming the radio lobe originated from the central AGN, we show the energy injection into the Inter Galactic Medium (IGM) is only sufficient to heat up the central 50 kpc within the cluster core, while the cooling radius is larger ( $\\sim$ 130 kpc). In the hardness ratio map, three low energy cavities have been identified. No radio emission is detected for these regions. We evaluated the power required to inflate the cavities and showed that the total energy budget is sufficient to offset the radiative cooling. We showed that the initial conditions would change the results remarkably. Furthermore, efficiency of Bondi accretion to power the AGN has been estimated.

  13. Primary metabolism and medium-chain fatty acid alterations precede long-chain fatty acid changes impacting neutral lipid metabolism in response to an anti-cancer lysophosphatidylcholine analogue in yeast.

    Science.gov (United States)

    Tambellini, Nicolas P; Zaremberg, Vanina; Krishnaiah, Saikumari; Turner, Raymond Joseph; Weljie, Aalim M

    2017-08-29

    The non-metabolizable lysophosphatidylcholine (LysoPC) analogue edelfosine is the prototype of a class of compounds being investigated for their potential as selective chemotherapeutic agents. Edelfosine targets membranes, disturbing cellular homeostasis. Is not clear at this point how membrane alterations are communicated between intracellular compartments leading to growth inhibition and eventual cell death. In the present study, a combined metabolomics/lipidomics approach for the unbiased identification of metabolic pathways altered in yeast treated with sub-lethal concentrations of the LysoPC analogue was employed. Mass spectrometry of polar metabolites, fatty acids and lipidomic profiling was used to study the effects of edelfosine on yeast metabolism. Amino acid and sugar metabolism, the Krebs cycle, and fatty acid profiles were most disrupted, with polar metabolites and short-medium chain fatty acid changes preceding long and very long-chain fatty acid variations. Initial increase in metabolites like trehalose, proline and gamma-amino butyric acid with a concomitant decrease in metabolites of the Krebs cycle, citrate and fumarate, are interpreted as a cellular attempt to offset oxidative stress in response to mitochondrial dysfunction induced by the treatment. Notably, alanine, inositol and myristoleic acid showed a steady increase during the period analyzed (2,4 and 6 hours after treatment). Of importance was the finding that edelfosine induced significant alterations in neutral glycerolipid metabolism resulting in a significant increase in the signalling lipid diacylglycerol.

  14. 9G4 autoreactivity is increased in HIV-infected patients and correlates with HIV broadly neutralizing serum activity.

    Directory of Open Access Journals (Sweden)

    James J Kobie

    Full Text Available The induction of a broadly neutralizing antibody (BNAb response against HIV-1 would be a desirable feature of a protective vaccine. Vaccine strategies thus far have failed to elicit broadly neutralizing antibody responses; however a minority of HIV-infected patients do develop circulating BNAbs, from which several potent broadly neutralizing monoclonal antibodies (mAbs have been isolated. The findings that several BNmAbs exhibit autoreactivity and that autoreactive serum antibodies are observed in some HIV patients have advanced the possibility that enforcement of self-tolerance may contribute to the rarity of BNAbs. To examine the possible breakdown of tolerance in HIV patients, we utilized the 9G4 anti-idiotype antibody system, enabling resolution of both autoreactive VH4-34 gene-expressing B cells and serum antibodies. Compared with healthy controls, HIV patients had significantly elevated 9G4+ serum IgG antibody concentrations and frequencies of 9G4+ B cells, a finding characteristic of systemic lupus erythematosus (SLE patients, both of which positively correlated with HIV viral load. Compared to the global 9G4-IgD--memory B cell population, the 9G4+IgD--memory fraction in HIV patients was dominated by isotype switched IgG+ B cells, but had a more prominent bias toward "IgM only" memory. HIV envelope reactivity was observed both in the 9G4+ serum antibody and 9G4+ B cell population. 9G4+ IgG serum antibody levels positively correlated (r = 0.403, p = 0.0019 with the serum HIV BNAbs. Interestingly, other serum autoantibodies commonly found in SLE (anti-dsDNA, ANA, anti-CL did not correlate with serum HIV BNAbs. 9G4-associated autoreactivity is preferentially expanded in chronic HIV infection as compared to other SLE autoreactivities. Therefore, the 9G4 system provides an effective tool to examine autoreactivity in HIV patients. Our results suggest that the development of HIV BNAbs is not merely a consequence of a general breakdown in

  15. Neutral Evolution of Mutational Robustness

    CERN Document Server

    Van Nimwegen, E; Huynen, M; Nimwegen, Erik van; Crutchfield, James P.; Huynen, Martijn

    1999-01-01

    We introduce and analyze a general model of a population evolving over a network of selectively neutral genotypes. We show that the population's limit distribution on the neutral network is solely determined by the network topology and given by the principal eigenvector of the network's adjacency matrix. Moreover, the average number of neutral mutant neighbors per individual is given by the matrix spectral radius. This quantifies the extent to which populations evolve mutational robustness: the insensitivity of the phenotype to mutations. Since the average neutrality is independent of evolutionary parameters---such as, mutation rate, population size, and selective advantage---one can infer global statistics of neutral network topology using simple population data available from {\\it in vitro} or {\\it in vivo} evolution. Populations evolving on neutral networks of RNA secondary structures show excellent agreement with our theoretical predictions.

  16. Identification of IgM as a contaminant in lectin-FLISA assays for HCC detection.

    Science.gov (United States)

    Wang, Mengjun; Comunale, Mary Ann; Herrera, Harmin; Betesh, Lucy; Kono, Yuko; Mehta, Anand

    2016-07-29

    Liver disease, in the form of hepatocellular carcinoma (HCC) accounts for > 700,000 deaths worldwide. A major reason for this is late diagnosis of HCC. The currently used biomarker, serum alpha-fetoprotein (AFP) is elevated in 40-60% of those with HCC and other markers that can either compliment or replace AFP are desired. Our previous work has identified a number of proteins that contain altered glycans in HCC. Specifically, these altered glycans were increased levels of core and outer arm fucosylation. To determine the clinical usefulness of those identified glycoproteins, a plate based assay was developed that allowed for the detection of fucosylated glycoforms. While this method was applicable to a number of independent patient sets, it was unable to specifically detect fucosylated glycoforms in many patient samples. That is, some material was present in serum that led to non-specific signal in the lectin- fluorescence -linked immunosorbent assay (lectin-FLISA). To address this issue, a systematic process was undertaken to identify the material. This material was found to be increased levels of lectin reactive IgM. Removal of both IgG and IgM using a multi-step protein A/G incubation and filtration step removed the contaminating signal and allowed for the analysis of specific protein glycoforms. This assay was subsequently used on two sample sets, one that was shown previously to be unable to be tested via a lectin FLISA and in a larger independent sample set. The clinical usefulness of this assay in the early detection of HCC is discussed.

  17. Strange neutral currents in nuclei

    CERN Document Server

    Ressell, M T; Aufderheide, M B; Bloom, S D; Resler, D A

    1995-01-01

    We examine the effects on the nuclear neutral current Gamow-Teller (GT) strength of a finite contribution from a polarized strange quark sea. We perform nuclear shell model calculations of the neutral current GT strength for a number of nuclei likely to be present during stellar core collapse. We compare the GT strength when a finite strange quark contribution is included to the strength without such a contribution. As an example, the process of neutral current nuclear de-excitation via \

  18. Aberrant levels of natural IgM antibodies in osteoarthritis and rheumatoid arthritis patients in comparison to healthy controls.

    Science.gov (United States)

    Nguyen, Tue G; McKelvey, Kelly J; March, Lyn M; Hunter, David J; Xue, Meilang; Jackson, Christopher J; Morris, Jonathan M

    2016-02-01

    Natural IgM antibodies (nIgM) are polyreactive autoantibodies that have diverse roles in regulating autoimmunity, systemic inflammation and removal of oxidized low-density lipoproteins (oxLDL). We hypothesized that aberrant states of nIgM may exist in persons with osteoarthritis (OA) and rheumatoid arthritis (RA). Herein, we characterized and compared the levels of nIgM specific for phosphorylcholine (anti-PC), double-stranded DNA (anti-dsDNA), and galactosyl (anti-Gal) in persons with OA, RA and healthy controls (HC). Levels of anti-PC nIgM in OA patients were significantly lower than both HC and RA patients in an age-adjusted analysis (P<0.05). In contrast, anti-Gal nIgM levels were significantly higher in RA patients than OA patients (P<0.05) and markedly increased in comparison to HC. Anti-PC nIgM significantly correlated with anti-dsDNA and anti-Gal nIgM levels in HC and RA (P<0.05) but not in OA patients. Elevated CRP levels were associated with RA conditions and old ages in general. There was no significant correlation between anti-PC nIgM and CRP or oxLDL levels. Our study highlights for the first time the evidence of aberrant state of nIgM in human OA compared to healthy individuals that implicates a deficiency in immune responses to oxLDL which may contribute to the metabolic syndromes in the development of OA.

  19. IgM and IgG antibodies to phenolic glycolipid I from Mycobacterium leprae in leprosy: insight into patient monitoring, erythema nodosum leprosum, and bacillary persistence.

    Science.gov (United States)

    Levis, W R; Meeker, H C; Schuller-Levis, G; Sersen, E; Schwerer, B

    1986-05-01

    Serum IgM and IgG antibodies against Mycobacterium leprae-derived phenolic glycolipid I (PG) were determined in leprosy patients, contacts, and controls by enzyme-linked immunosorbent assay (ELISA). Anti-PG IgM levels increased from the tuberculoid (TT) to the lepromatous (LL) pole of the disease spectrum. There was a positive linear correlation between anti-PG IgM and bacillary index (BI). Patients with erythema nodosum leprosum (ENL) had lower levels of serum anti-PG IgM than non-ENL patients of comparable BI, suggesting that anti-PG IgM is involved in the pathogenesis of ENL. Initial observations indicate that high anti-PG IgM levels in bacillary-negative patients might reflect bacillary persistence. A study of 2 different substrate reagents in the ELISA [2,2'-azino-di(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), 0.1 mM H2O2, serum diluted 1:20, and o-phenylenediamine (OPD), 5 mM H2O2, serum diluted 1:300] showed generally good correlation in detection of anti-PG IgM. However the OPD system detected more paucibacillary disease (BT), while the ABTS system detected the significant effect of ENL on the relationship between BI and anti-PG IgM. Anti-PG IgM was clearly dominant over anti-PG IgG. However, certain patients, including several patients who had upgraded from LL and borderline lepromatous leprosy (BL), showed high levels of anti-PG IgG. Since studies have shown that LL patients are selectively deficient in cell-mediated immunity, T-cell products may be required for the IgM to IgG isotype switch. We conclude that anti-PG IgM is useful for monitoring the bacillary load in individual patients and should prove useful for leprosy control strategies.

  20. Identification and specificity of broadly neutralizing antibodies against HIV

    OpenAIRE

    McCoy, Laura E.; Burton, Dennis R.

    2017-01-01

    Summary Beginning in 2009, studies of the humoral responses of HIV‐positive individuals have led to the identification of scores, if not hundreds, of antibodies that are both broadly reactive and potently neutralizing. This development has provided renewed impetus toward an HIV vaccine and led directly to the development of novel immunogens. Advances in identification of donors with the most potent and broad anti‐HIV serum neutralizing responses were crucial in this effort. Equally, developme...

  1. A focus reduction neutralization assay for hepatitis C virus neutralizing antibodies

    Directory of Open Access Journals (Sweden)

    Wychowski Czeslaw

    2007-03-01

    Full Text Available Abstract Background/Aim The role of humoral immunity in hepatitis C virus (HCV infection is poorly understood. Nevertheless, there is increasing interest in characterizing the neutralizing antibodies in the serum of HCV-infected patients. Focus reduction assays have been widely used to evaluate neutralizing antibody responses against a range of non-cytopathic viruses. Based on the recent development of a HCV cell culture system using the genotype 2 JFH-1-strain, we developed a focus reduction assay for HCV-neutralizing antibodies. Methods The focus reduction assay was based on a standard microneutralization assay in which immunostained foci on tissue culture plates are counted. The neutralizing anti-HCV antibodies titers of purified serum immunoglobulin samples from seventy-seven individuals were determined using a 50% focus reduction neutralization assay. Each titer was determined as the log value of the reciprocal antibody dilution that reduced the number of viral foci by 50%. IgG antibodies were first purified from each serum in order to avoid the facilitating effect of HDL on HCV entry. Results The assay's cut-off using an ELISA and RNA HCV-negative samples was found to be 1.25 log, corresponding to a dilution of 1:18. The assay was compared with a commercial HCV ELISA and exhibited specificity and sensitivity values of 100% and 96.5%, respectively, and good reproducibility (with intra-assay and inter-assay coefficients of variation of 6.7% and 12.6%, respectively. The assay did not show any cross-reactivity with anti-HIV, anti-HBs or heterophile antibody-positive samples. The neutralizing antibodies titers were 2.13 log (1:134 for homologous samples from HCV genotype 2 infected patients harboring the same genotype as JFH-1 and 1.93 log (1:85 for heterologous samples from patients infected by genotypes other than type 2. These results confirm the presence of broadly cross-neutralizing antibodies already reported using the HCV pseudoparticles

  2. Constraining the Europa Neutral Torus

    Science.gov (United States)

    Smith, Howard T.; Mitchell, Donald; mauk, Barry; Johnson, Robert E.; clark, george

    2016-10-01

    "Neutral tori" consist of neutral particles that usually co-orbit along with their source forming a toroidal (or partial toroidal) feature around the planet. The distribution and composition of these features can often provide important, if not unique, insight into magnetospheric particles sources, mechanisms and dynamics. However, these features can often be difficult to directly detect. One innovative method for detecting neutral tori is by observing Energetic Neutral Atoms (ENAs) that are generally considered produced as a result of charge exchange interactions between charged and neutral particles.Mauk et al. (2003) reported the detection of a Europa neutral particle torus using ENA observations. The presence of a Europa torus has extremely large implications for upcoming missions to Jupiter as well as understanding possible activity at this moon and providing critical insight into what lies beneath the surface of this icy ocean world. However, ENAs can also be produced as a result of charge exchange interactions between two ionized particles and in that case cannot be used to infer the presence of neutral particle population. Thus, a detailed examination of all possible source interactions must be considered before one can confirm that likely original source population of these ENA images is actually a Europa neutral particle torus. For this talk, we examine the viability that the Mauk et al. (2003) observations were actually generated from a neutral torus emanating from Europa as opposed to charge particle interactions with plasma originating from Io. These results help constrain such a torus as well as Europa source processes.

  3. A large neutral fraction of cosmic hydrogen a billion years after the Big Bang.

    Science.gov (United States)

    Wyithe, J Stuart B; Loeb, Abraham

    2004-02-26

    The fraction of ionized hydrogen left over from the Big Bang provides evidence for the time of formation of the first stars and quasar black holes in the early Universe; such objects provide the high-energy photons necessary to ionize hydrogen. Spectra of the two most distant known quasars show nearly complete absorption of photons with wavelengths shorter than the Lyman alpha transition of neutral hydrogen, indicating that hydrogen in the intergalactic medium (IGM) had not been completely ionized at a redshift of z approximately 6.3, about one billion years after the Big Bang. Here we show that the IGM surrounding these quasars had a neutral hydrogen fraction of tens of per cent before the quasar activity started, much higher than the previous lower limits of approximately 0.1 per cent. Our results, when combined with the recent inference of a large cumulative optical depth to electron scattering after cosmological recombination therefore suggest the presence of a second peak in the mean ionization history of the Universe.

  4. Immunopotentiality of Ayurvedic polyherbal formulations “Saribadi” and “Anantamul Salsa” with augmentation of IgM production and lymphocytes proliferation:A preliminary study

    Institute of Scientific and Technical Information of China (English)

    Md.Moklesur Rahman Sarker; Long Chiau Ming; Md.Zaidul Islam Sarker; M Shahabuddin Kabir Choudhuri

    2016-01-01

    Objective:To assess the immunopotentiality of Ayurvedic polyherbal preparations,"Saribadi" and "Anantamul Salsa".Methods: Freshly prepared BALB/c mice splenocytes were cultured with "Saribadi" or"Anantamul Salsa" treatment [doses of 0.25%, 0.50%, 0.75%, 1.00%, 1.50%, 2.00%,3.00% and 4.00%(v/v)] at 37C for 5 days. The immunoglobulin M(IgM) production and lymphocytes proliferation were determined by ELISA and MTT methods, respectively.Endotoxin contamination was assessed by treating the preparations with polymyxin B.Results: The doses of "Saribadi" [0.25%, 0.50%, 0.75% and 1.00%(v/v)] significantly increased IgM productions(0.966, 0.728, 0.695 and 0.615 mg/m L vs. control 0.265 mg/m L)and lymphocytes proliferation [absorbance 0.311, 0.394, 0.372 and 0.334 optical density(OD) vs. control 0.162 OD]. Similarly, the doses of "Anantamul Salsa" [0.50%, 0.75%,1.00% and 1.50%(v/v)] promoted IgM productions(0.933, 0.919, 0.917 and 0.892 mg/m L vs. control 0.502 mg/m L) and the doses of "Anantamul Salsa" [0.50%, 0.75%, 1.00%,1.50%, 2.00%, and 3.00%(v/v)] stimulated lymphocytes proliferation(absorbance 0.395,0.326, 0.440, 0.398, 0.452 and 0.355 OD vs. control 0.199 OD). The activity of "Saribadi"and "Anantamul Salsa" was not retarded by the treatment of preparations with polymyxin B.Conclusions: Immunomodulatory activity of "Saribadi" and "Anantamul Salsa" was unveiled for the first time. "Saribadi" and "Anantamul Salsa" possess immunostimulating potential acting through the induction of lymphocyte proliferation and IgM production.These preparations may be useful in strengthening immune responses. However, further cellular and in vivo studies are required.

  5. HIV-1 binding and neutralizing antibodies of injecting drug users

    Directory of Open Access Journals (Sweden)

    Ouverney E.P.

    2005-01-01

    Full Text Available Previous studies have demonstrated a stronger seroreactivity against some synthetic peptides responsible for inducing neutralizing antibodies in injecting drug users (IDU compared to that of individuals sexually infected with HIV-1 (S, but the effectiveness in terms of the neutralizing ability of these antibodies has not been evaluated. Our objective was to study the humoral immune response of IDU by determining the specificity of their antibodies and the presence of neutralizing antibodies. The neutralization capacity against the HIV-1 isolate MN (genotype B, the primary HIV-1 isolate 95BRRJ021 (genotype F, and the seroreactivity with peptides known to induce neutralizing antibodies, from the V2 and V3 loops of different HIV-1 subtypes, were analyzed. Seroreactivity indicates that IDU plasma are more likely to recognize a broader range of peptides than S plasma, with significantly higher titers, especially of V3 peptides. Similar neutralization frequencies of the MN isolate were observed in plasma of the IDU (16/47 and S (20/60 groups in the 1:10 dilution. The neutralization of the 95BRRJ021 isolate was more frequently observed for plasma from the S group (15/23 than from the IDU group (15/47, P = 0.0108. No correlation between neutralization and seroreactivity with the peptides tested was observed. These results suggest that an important factor responsible for the extensive and broad humoral immune response observed in IDU is their infection route. There was very little difference in neutralizing antibody response between the IDU and S groups despite their differences in seroreactivity and health status.

  6. CO2-neutral fuels

    Science.gov (United States)

    Goede, A. P. H.

    2015-08-01

    The need for storage of renewable energy (RE) generated by photovoltaic, concentrated solar and wind arises from the fact that supply and demand are ill-matched both geographically and temporarily. This already causes problems of overcapacity and grid congestion in countries where the fraction of RE exceeds the 20% level. A system approach is needed, which focusses not only on the energy source, but includes conversion, storage, transport, distribution, use and, last but not least, the recycling of waste. Furthermore, there is a need for more flexibility in the energy system, rather than relying on electrification, integration with other energy systems, for example the gas network, would yield a system less vulnerable to failure and better adapted to requirements. For example, long-term large-scale storage of electrical energy is limited by capacity, yet needed to cover weekly to seasonal demand. This limitation can be overcome by coupling the electricity net to the gas system, considering the fact that the Dutch gas network alone has a storage capacity of 552 TWh, sufficient to cover the entire EU energy demand for over a month. This lecture explores energy storage in chemicals bonds. The focus is on chemicals other than hydrogen, taking advantage of the higher volumetric energy density of hydrocarbons, in this case methane, which has an approximate 3.5 times higher volumetric energy density. More importantly, it allows the ready use of existing gas infrastructure for energy storage, transport and distribution. Intermittent wind electricity generated is converted into synthetic methane, the Power to Gas (P2G) scheme, by splitting feedstock CO2 and H2O into synthesis gas, a mixture of CO and H2. Syngas plays a central role in the synthesis of a range of hydrocarbon products, including methane, diesel and dimethyl ether. The splitting is accomplished by innovative means; plasmolysis and high-temperature solid oxygen electrolysis. A CO2-neutral fuel cycle is

  7. CO2-neutral fuels

    Directory of Open Access Journals (Sweden)

    Goede A. P. H.

    2015-01-01

    Full Text Available The need for storage of renewable energy (RE generated by photovoltaic, concentrated solar and wind arises from the fact that supply and demand are ill-matched both geographically and temporarily. This already causes problems of overcapacity and grid congestion in countries where the fraction of RE exceeds the 20% level. A system approach is needed, which focusses not only on the energy source, but includes conversion, storage, transport, distribution, use and, last but not least, the recycling of waste. Furthermore, there is a need for more flexibility in the energy system, rather than relying on electrification, integration with other energy systems, for example the gas network, would yield a system less vulnerable to failure and better adapted to requirements. For example, long-term large-scale storage of electrical energy is limited by capacity, yet needed to cover weekly to seasonal demand. This limitation can be overcome by coupling the electricity net to the gas system, considering the fact that the Dutch gas network alone has a storage capacity of 552 TWh, sufficient to cover the entire EU energy demand for over a month. This lecture explores energy storage in chemicals bonds. The focus is on chemicals other than hydrogen, taking advantage of the higher volumetric energy density of hydrocarbons, in this case methane, which has an approximate 3.5 times higher volumetric energy density. More importantly, it allows the ready use of existing gas infrastructure for energy storage, transport and distribution. Intermittent wind electricity generated is converted into synthetic methane, the Power to Gas (P2G scheme, by splitting feedstock CO2 and H2O into synthesis gas, a mixture of CO and H2. Syngas plays a central role in the synthesis of a range of hydrocarbon products, including methane, diesel and dimethyl ether. The splitting is accomplished by innovative means; plasmolysis and high-temperature solid oxygen electrolysis. A CO2-neutral fuel

  8. Neutralizing antibodies to Haemophilus ducreyi cytotoxin.

    OpenAIRE

    Lagergård, T; Purvén, M

    1993-01-01

    Neutralizing antibodies against cytotoxin produced by Haemophilus ducreyi bacteria were studied in rabbits by an assay employing HEp-2 cells and diluted crude cytotoxin preparations from the organism. Antisera to 12 different H. ducreyi strains were prepared by immunization of rabbits with bacterial sonicates combined with Freund's adjuvant. The antibody response during infection with H. ducreyi was studied in two groups of rabbits which were infected with five live strains by either single o...

  9. Elucidation of the potential disease-promoting influence of IgM apoptotic cell-reactive antibodies in lupus.

    Science.gov (United States)

    Malik, M; Arora, P; Sachdeva, R; Sharma, L; Ramachandran, V G; Pal, R

    2016-06-01

    The undigested remnants of apoptosis are believed to stimulate the generation of autoantibodies in lupus. The biological properties of initiator, disease-specific IgM antibodies that specifically recognize apoptotic cells, readily detected in the sera of lupus patients, remain unclear. Apoptotic cell-reactive IgM monoclonal antibodies (generated from lupus-prone mice), as opposed to control IgM, preferentially stimulated maturation of bone marrow-derived dendritic cells (BMDCs) derived from such mice, relative to BMDCs derived from healthy mice. An influence of both antibody specificity and cell genotype was also apparent in the secretion of signature inflammatory cytokines. Immunization of such antibodies in lupus-prone animals induced increases in total serum IgG levels, with the elicited antibodies also preferentially recognizing moieties on dying cells. An expanded specificity was apparent both upon Western blot on cellular lysate and from the enhanced recognition of dsDNA, Ro60, RNP68 and Sm; the antibody most efficient in mediating autoreactive diversity, while being germline encoded, also induced the highest degree of phenotypic changes on BMDCs. Apoptotic cell-reactive IgM antibodies may therefore be potentially capable of influencing the course of systemic autoimmune disease by affecting both innate and adaptive immunity.

  10. Circadian type, chronic fatigue, and serum IgM in the shift workers of an industrial organization

    Directory of Open Access Journals (Sweden)

    Shahnaz Khaleghipour

    2015-01-01

    Conclusion: The results showed that the shift workers with morningness and languidness experienced more problems during the working hours due to more tiredness,and had decreased serum concentration of IgM. Correct management of shift work may attenuate fatigue in workers and also improve many health issues experienced by the shift workers.

  11. Mapping the low-surface brightness Universe in the UV band with Lyα emission from IGM filaments

    NARCIS (Netherlands)

    Silva, Marta B.; Kooistra, Robin; Zaroubi, Saleem

    2016-01-01

    A large fraction of the baryonic matter in the Universe is located in filaments in the intergalactic medium (IGM). However, the low surface brightness of these filaments has not yet allowed their direct detection except in very special regions in the circum-galactic medium. Here we simulate the

  12. Raman spectroscopy-based screening of IgM positive and negative sera for dengue virus infection

    Science.gov (United States)

    Bilal, M.; Saleem, M.; Bilal, Maria; Ijaz, T.; Khan, Saranjam; Ullah, Rahat; Raza, A.; Khurram, M.; Akram, W.; Ahmed, M.

    2016-11-01

    A statistical method based on Raman spectroscopy for the screening of immunoglobulin M (IgM) in dengue virus (DENV) infected human sera is presented. In total, 108 sera samples were collected and their antibody indexes (AI) for IgM were determined through enzyme-linked immunosorbent assay (ELISA). Raman spectra of these samples were acquired using a 785 nm wavelength excitation laser. Seventy-eight Raman spectra were selected randomly and unbiasedly for the development of a statistical model using partial least square (PLS) regression, while the remaining 30 were used for testing the developed model. An R-square (r 2) value of 0.929 was determined using the leave-one-sample-out (LOO) cross validation method, showing the validity of this model. It considers all molecular changes related to IgM concentration, and describes their role in infection. A graphical user interface (GUI) platform has been developed to run a developed multivariate model for the prediction of AI of IgM for blindly tested samples, and an excellent agreement has been found between model predicted and clinically determined values. Parameters like sensitivity, specificity, accuracy, and area under receiver operator characteristic (ROC) curve for these tested samples are also reported to visualize model performance.

  13. A clinical and neurobiological case of IgM NMDA receptor antibody associated encephalitis mimicking bipolar disorder.

    Science.gov (United States)

    Choe, Chi-Un; Karamatskos, Evangelos; Schattling, Benjamin; Leypoldt, Frank; Liuzzi, Gianpiero; Gerloff, Christian; Friese, Manuel A; Mulert, Christoph

    2013-07-30

    Autoimmune encephalitis associated with IgG antibodies to the N-methyl-d-aspartic acid receptor subunit NR1 (NMDAR) presents with neurological symptoms, such as seizures, and especially psychiatric symptoms, such as hallucinations, psychosis, agitation and anxiety. To date, however, the pathological relevance of IgM NMDAR antibodies remains elusive. Here, we describe clinical, neuroradiological and neurobiological findings of a 28-year-old male presenting with IgM NMDAR antibodies coincident with autoimmune encephalitis characterized by symptoms of bipolar disorder. After repeated steroid treatment, cognitive and psychiatric abnormalities improved and no NMDAR antibody was detectable. Using primary neuronal cultures, we demonstrate that patient's serum containing IgM NMDAR antibodies reduced the detection of NMDAR on neuronal cells and decreased cell survival. Although NMDAR encephalitis with IgG antibodies is increasingly recognized and diagnosed, atypical presentations with NMDAR antibodies with immunoglobulin subclasses other than IgG pose a diagnostic and therapeutic challenge. Further clinical and neurobiological studies are needed to study the pathophysiological relevance of IgM NMDAR antibodies.

  14. Simultaneous use of serum IgG and IgM for risk scoring of suspected early Lyme borreliosis: graphical and bivariate analyses

    DEFF Research Database (Denmark)

    Dessau, Ram; Ejlertsen, Tove; Hilden, Jørgen

    2010-01-01

    The laboratory diagnosis of early disseminated Lyme borreliosis (LB) rests on IgM and IgG antibodies in serum. The purpose of this study was to refine the statistical interpretation of IgM and IgG by combining the diagnostic evidence provided by the two immunoglobulins and exploiting the whole ra...

  15. Cross-reactions in IgM ELISA tests to Legionella pneumophila sg1 and Bordetella pertussis among children suspected of legionellosis; potential impact of vaccination against pertussis?

    Science.gov (United States)

    Pancer, Katarzyna Wanda

    2015-01-01

    The objective of this study was preliminary evaluation of IgM cross-reaction in sera collected from children hospitalized because of suspected legionellosis. Sera with positive IgM results to L. pneumophila sgs1-7, B. pertussis or with simultaneous detection of IgM antibodies to L. pneumophila sgs1-7 and B. pertussis, or IgM to L. pneumophila sgs1-7 and M. pneumoniae in routine tests, were selected. In total, an adapted pre-absorption test was used for the serological confirmation of legionellosis in the sera of 19 children suspected of legionellosis, and also in 3 adult persons with confirmed Legionnaires' disease. Sera were pre-absorbed with antigens of L. pneumophila sg1, B. pertussis or both, and tested by ELISA tests. The reduction of IgM antibody level by pre-absorption with antigen/antigens was determined. Reduction of anti-Lpsgs1-7 IgM by pre-absorption with L.pneumophila sg1 antigen ranged from 1.5 to 80, and reduction of anti-Bp IgM by pre-absorption with B. pertussis ranged from 2.0 to 23.8. Reduction by both antigens varied depending on the age of the patients: among children tests. As a preliminary, we posed a hypothesis of a potential impact of an anti-pertussis vaccination on the results obtained in anti-L. pneumophila ELISA IgM tests among young children.

  16. Intraprostatic injection of neutralized zinc in rats

    Energy Technology Data Exchange (ETDEWEB)

    Fahim, M.S.; Wang, M.; Sutcu, M.F.; Fahim, Z.; Safron, J.A.; Ganjam, V.K. (Univ. of Missouri, Columbia (United States) Xian Medical University (China))

    1991-03-11

    Zinc has been implicated in steroid endocrinology of the prostate gland. The conversion of testosterone to dihydrotestosterone (DHT) by 5{alpha}-reductase enzyme is believed to express androgenic responses in the prostate. To note the effect of neutralized zinc on the prostate, 50 sexually mature rats, weighing 325 {plus minus} 20 grams, were divided into 5 groups as follows: (1) control, (2) sham, (3) castrated, (4) injected intraprostatically with 10 mg. neutralized zinc, and (5) injected intraprostatically with 20 mg. neutralized zinc. Results in the treated groups indicated significant reduction of prostate weights, 12% and 53% and histologically normal prostate; no significant change in weight and histological structure of testes, epididymides, and seminal vesicles; significant reduction in 5{alpha}-reductase activity and total protein and DNA concentrations in prostate tissue; and no significant effect on progeny of treated animals. These results suggest that direct application of neutralized zinc to the prostate offers a new modality for treatment of prostatitis without affecting spermatogenesis and testosterone production.

  17. Attenuation of skeletal muscle reperfusion injury with intravenous 12 amino acid peptides that bind to pathogenic IgM.

    Science.gov (United States)

    Chan, Rodney K; Verna, Nicola; Afnan, Jalil; Zhang, Ming; Ibrahim, Shahrul; Carroll, Michael C; Moore, Francis D

    2006-02-01

    The injury sustained by reperfused skeletal muscle is inflammatory and is initiated by binding of pre-formed IgM to involved tissue, followed by local complement activation and further inflammation. A clone of natural IgM has been described that initiates this injury, suggesting that specific antigens are exposed on ischemic tissues that act as ligands for this pathogenic antibody. In these experiments, we examine the properties of short peptide sequences, and their homologues, that bind to the antigen-combining site of this pathogenic IgM clone. A 12-mer phage display library was biopanned with the pathogenic IgM clone and then negatively selected against an inactive natural IgM clone. All 8 clones that bound specifically to the pathogenic IgM had closely related amino acid sequences. P8 is the clone that bound most avidly. Tissue lysates from ischemic tissue were reacted with pathogenic IgM, and immune complexes isolated and analyzed on SDS-PAGE. Bands were excised and sequenced, identifying non-muscle myosin as the protein reacting with pathogenic antibody in ischemic gut and glycogen phosphorylase as the counterpart in ischemic skeletal muscle. Both proteins contain sequence homologous to P8; N2 and GP1 are the natural 12-mers homologues that are contained within non-muscle myosin and glycogen phosphorylase, respectively. Wild-type C57/Bl6 mice, divided into groups receiving saline, P8, N2, GP1, or a random peptide at the start of the experiment, were subjected to 2 hours of tourniquet induced hind limb ischemia and 3 hours of reperfusion. Muscle was assessed for injury with histology and for immune activation with histochemistry. Intravenous administration of P8, N2, and GP1 led to significant attenuation of muscle injury (13 +/- 1.8 injured fibers/50 counted, 12 +/- 0.81, 8.0 +/- 0.73 respectively) after reperfusion injury compared to animals receiving saline (26 +/- 2.3) or the same mass of a random peptide (22 +/- 2.3), P less than .05. This level of

  18. The merits of neutral theory

    NARCIS (Netherlands)

    Alonso, David; Etienne, Rampal S.; McKane, Alan J.

    2006-01-01

    Hubbell's neutral theory of biodiversity has challenged the classic niche-based view of ecological community structure. Although there have been many attempts to falsify Hubbell's theory, we argue that falsification should not lead to rejection, because there is more to the theory than neutrality al

  19. The merits of neutral theory

    NARCIS (Netherlands)

    Alonso, D.; Etienne, R.S.; McKane, A.J.

    2006-01-01

    Hubbell's neutral theory of biodiversity has challenged the classic niche-based view of ecological community structure. Although there have been many attempts to falsify Hubbell's theory, we argue that falsification should not lead to rejection, because there is more to the theory than neutrality al

  20. Neutral evolution of mutational robustness.

    NARCIS (Netherlands)

    Nimwegen, E. van; Crutchfield, J.P.; Huynen, M.A.

    1999-01-01

    We introduce and analyze a general model of a population evolving over a network of selectively neutral genotypes. We show that the population's limit distribution on the neutral network is solely determined by the network topology and given by the principal eigenvector of the network's adjacency ma

  1. Results of anti-Toxoplasma gondii IgG, IgM, IgA and IgG Avidity testing in pregnant women in Rome, Italy

    Directory of Open Access Journals (Sweden)

    Carla Nisii

    2012-12-01

    Full Text Available To evaluate the incidence of Toxoplasma gondii infection, the detection of specific IgG, IgM, IgA and IgG avidity was performed on 1424 pregnant women referred to the “L. Spallanzani” Hospital in Rome (Italy. Of the 1424 women screened, 20 (1.40% were likely to have been recently infected (presence of IgM/IgA, and/or low IgG avidity, 29 (2.04% had positive IgM coupled with high IgG avidity, 7 (0.49% had an unspecific result for IgM alone, 1339 (94.0%, were negative for both IgG and IgM, 29 (2.04% showed evidence of past infection (IgG positive, IgM negative, high IgG avidity. In Conclusion our results underscore the importance of efficient antenatal screening and appropriate treatment for Toxoplasma infection in Italy.

  2. Separation and concentration effect of f-MWCNTs on electrocatalytic responses of ascorbic acid, dopamine and uric acid at f-MWCNTs incorporated with poly (neutral red) composite films

    Energy Technology Data Exchange (ETDEWEB)

    Yogeswaran, Umasankar [Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, No.1, Section 3, Chung-Hsiao East Road, Taipei 106, Taiwan (China); Chen, Shen-Ming [Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, No.1, Section 3, Chung-Hsiao East Road, Taipei 106, Taiwan (China)]. E-mail: smchen78@ms15.hinet.net

    2007-05-25

    A novel conductive composite film containing functionalized multi-walled carbon nanotubes (f-MWCNTs) with poly (neutral red) (PNR) was synthesized on glassy carbon electrodes (GC) by potentiostatic method. The composite film exhibited promising electrocatalytic oxidation of mixture of biochemical compounds such as ascorbic acid (AA), dopamine (DA) and uric acid (UA) in pH 4.0 aqueous solutions. It was also produced on gold electrodes by using electrochemical quartz crystal microbalance technique, which revealed that the functional properties of composite film were enhanced because of the presence of both f-MWCNTs and PNR. The surface morphology of the polymer and composite film deposited on transparent semiconductor tin oxide electrodes were studied using scanning electron microscopy and atomic force microscopy. These two techniques showed that the PNR was fibrous and incorporated on f-MWCNTs. The electrocatalytic responses of neurotransmitters at composite films were measured using both cyclic voltammetry (CV) and differential pulse voltammetry (DPV). These experiments revealed that the difference in f-MWCNTs loading present in the composite film affected the electrocatalysis in such a way, that higher the loading showed an enhanced electrocatalytic activity. From further electrocatalysis studies, well separated voltammetric peaks were obtained at the composite film modified GC for AA, DA and UA with the peak separation of 0.17 V between AA-DA and 0.15 V between DA-UA. The sensitivity of the composite film towards AA, DA and UA in DPV technique was found to be 0.028, 0.146 and 0.084 {mu}A {mu}M{sup -1}, respectively.

  3. Viral escape from HIV-1 neutralizing antibodies drives increased plasma neutralization breadth through sequential recognition of multiple epitopes and immunotypes.

    Directory of Open Access Journals (Sweden)

    Constantinos Kurt Wibmer

    2013-10-01

    Full Text Available Identifying the targets of broadly neutralizing antibodies to HIV-1 and understanding how these antibodies develop remain important goals in the quest to rationally develop an HIV-1 vaccine. We previously identified a participant in the CAPRISA Acute Infection Cohort (CAP257 whose plasma neutralized 84% of heterologous viruses. In this study we showed that breadth in CAP257 was largely due to the sequential, transient appearance of three distinct broadly neutralizing antibody specificities spanning the first 4.5 years of infection. The first specificity targeted an epitope in the V2 region of gp120 that was also recognized by strain-specific antibodies 7 weeks earlier. Specificity for the autologous virus was determined largely by a rare N167 antigenic variant of V2, with viral escape to the more common D167 immunotype coinciding with the development of the first wave of broadly neutralizing antibodies. Escape from these broadly neutralizing V2 antibodies through deletion of the glycan at N160 was associated with exposure of an epitope in the CD4 binding site that became the target for a second wave of broadly neutralizing antibodies. Neutralization by these CD4 binding site antibodies was almost entirely dependent on the glycan at position N276. Early viral escape mutations in the CD4 binding site drove an increase in wave two neutralization breadth, as this second wave of heterologous neutralization matured to recognize multiple immunotypes within this site. The third wave targeted a quaternary epitope that did not overlap any of the four known sites of vulnerability on the HIV-1 envelope and remains undefined. Altogether this study showed that the human immune system is capable of generating multiple broadly neutralizing antibodies in response to a constantly evolving viral population that exposes new targets as a consequence of escape from earlier neutralizing antibodies.

  4. The Antiparticles of Neutral Bosons

    CERN Document Server

    Perkins, Walton A

    2013-01-01

    With the advent of the ability to create and study antihydrogen, we think it is appropriate to consider the possibility that antiphotons might not be identical to photons. First of all, we will look at the experimental evidence concerning multiple neutral pions and multiple photons. Because of its internal structure, the neutral kaon is not identical to its antiparticle. We will consider internal structures for the neutral pion and photon for which the antiparticle differs from the particle. Interestingly, the antiphoton thus created from neutrinos does not interact with electrons because its neutrinos have the wrong helicity.

  5. Positional nystagmus showing neutral points.

    Science.gov (United States)

    Hiruma, Kiyoshi; Numata, Tsutomu

    2004-01-01

    We encountered patients who had their static direction-changing positional nystagmus canceled at about 20-30 degrees yaw head rotation from the supine position. This nystagmus was also canceled when the head was rotated 180 degrees from this position. We call these head positions neutral points. At the neutral points, the cupula of the horizontal semicircular canal of the affected ear is positioned vertical to the gravitational plane and no deflection of the cupula occurs. The positional nystagmus observed (except the neutral points) was thought to occur due to a "heavy cupula" or "light cupula", which may be determined by the specific gravity of its endolymph.

  6. ELISA detection of specific functional antibodies in human serum to Escherichia coli, tetanus toxoid, and diphtheria-tetanus toxoids: normal values for IgG, IgA, and IgM.

    Science.gov (United States)

    Moen, R C; Oemichen, S L; Kiggens, A J; Hong, R

    1986-01-01

    An inexpensive, easily performed enzyme-linked immunosorbent assay (ELISA) was developed to measure specific IgG, IgA, and IgM antibodies to the common antigens Escherichia coli, diphtheria-tetanus toxoid, and tetanus toxoid. Normal values were established. Classical antibody deficiency disease states were confirmed and delineated by these assays. Additionally, several instances were discovered when functional antibody levels were abnormal when the serum immunoglobulin levels were normal. The use of ELISA assays for antibodies to common antigens provides a useful technique to measure and monitor isotype responses of the humoral immune system.

  7. Late Reheating of the IGM by Quasars: A Radiation Hydrodynamical Simulation of Helium II Reionization

    CERN Document Server

    Paschos, Pascal; Bordner, James O; Harkness, Robert

    2007-01-01

    We study the ionization and thermal evolution of the intergalactic medium during the epoch of \\heii reionization by means of radiation hydrodynamical cosmological simulations. We post-process baryonic density fields from a standard optically-thin IGM simulation with a homogeneous galaxy-dominated UV background (UVB) which reionizes \\hi and \\hei at z=6.5 but does not have any contribution to the ionization of \\heii. Quasars with luminosities proportional to the mass of the host halos are then introduced as point sources throughout the 100 Mpc simulation volume consistent with the Pei luminosity function. We evolve the spatial distribution of the \\heii ionizing radiation field using a time-implicit variable tensor Eddington factor radiative transfer scheme. Simultaneously, we also solve for the local ionization of \\heii to \\heii and the associated photoheating of the gas. We find that the percolation of the \\heiii regions is essentially complete by z=2.5. When comparing to a self-consistent optically thin simul...

  8. Lyalpha versus X-ray heating in the high-z IGM

    CERN Document Server

    Ciardi, Benedetta; Di Matteo, Tiziana

    2009-01-01

    In this paper we examine the effect of X-ray and Lyalpha photons on the intergalactic medium temperature. We calculate the photon production from a population of stars and micro-quasars in a set of cosmological hydrodynamic simulations which self-consistently follow the dark matter dynamics, radiative processes as well as star formation, black hole growth and associated feedback processes. We find that, (i) IGM heating is always dominated by X-rays unless the Lyalpha photon contribution from stars in objects with mass M<10^8 Msun becomes significantly enhanced with respect to the X-ray contribution from BHs in the same halo (which we do not directly model). (ii) Without overproducing the unresolved X-ray background, the gas temperature becomes larger than the CMB temperature, and thus an associated 21 cm signal should be expected in emission, at z<11.5. We discuss how in such a scenario the transition redshift between a 21 cm signal in absorption and in emission could be used to constraint BHs accretion...

  9. Relative contributions of neutral and non-neutral genetic differentiation to inform conservation of steelhead trout across highly variable landscapes

    Science.gov (United States)

    Matala, Andrew P; Ackerman, Michael W; Campbell, Matthew R; Narum, Shawn R

    2014-01-01

    Mounting evidence of climatic effects on riverine environments and adaptive responses of fishes have elicited growing conservation concerns. Measures to rectify population declines include assessment of local extinction risk, population ecology, viability, and genetic differentiation. While conservation planning has been largely informed by neutral genetic structure, there has been a dearth of critical information regarding the role of non-neutral or functional genetic variation. We evaluated genetic variation among steelhead trout of the Columbia River Basin, which supports diverse populations distributed among dynamic landscapes. We categorized 188 SNP loci as either putatively neutral or candidates for divergent selection (non-neutral) using a multitest association approach. Neutral variation distinguished lineages and defined broad-scale population structure consistent with previous studies, but fine-scale resolution was also detected at levels not previously observed. Within distinct coastal and inland lineages, we identified nine and 22 candidate loci commonly associated with precipitation or temperature variables and putatively under divergent selection. Observed patterns of non-neutral variation suggest overall climate is likely to shape local adaptation (e.g., potential rapid evolution) of steelhead trout in the Columbia River region. Broad geographic patterns of neutral and non-neutral variation demonstrated here can be used to accommodate priorities for regional management and inform long-term conservation of this species. PMID:25067950

  10. Post-learning psychosocial stress enhances consolidation of neutral stimuli.

    Science.gov (United States)

    Preuss, Diana; Wolf, Oliver T

    2009-10-01

    Post-learning stress has been reported to enhance memory consolidation in humans. This effect was observed in studies using physical stressors or an anticipatory speech task. In the present study 58 participants (28 females and 30 males) were exposed to a psychosocial stressor (Trier Social Stress Test) or a control condition following the presentation of neutral and emotionally arousing positive and negative pictures, which were accompanied by a brief narrative. The stressor induced a significant neuroendocrine stress response in men and women. In a 24h delayed free recall test the stress group showed an enhanced memory for neutral but not for emotionally arousing positive and negative items. Additionally, a significant correlation between the cortisol stress response and memory for neutral items was evident. Thus, in contrast to previous studies, post-learning stress primarily enhanced consolidation of neutral material. Several theoretical and methodological explanations for the observed effects are discussed.

  11. Neutrality Versus Materiality: A Thermodynamic Theory of Neutral Surfaces

    Directory of Open Access Journals (Sweden)

    Rémi Tailleux

    2016-09-01

    Full Text Available In this paper, a theory for constructing quasi-neutral density variables γ directly in thermodynamic space is formulated, which is based on minimising the absolute value of a purely thermodynamic quantity J n . Physically, J n has a dual dynamic/thermodynamic interpretation as the quantity controlling the energy cost of adiabatic and isohaline parcel exchanges on material surfaces, as well as the dependence of in-situ density on spiciness, in a description of water masses based on γ, spiciness and pressure. Mathematically, minimising | J n | in thermodynamic space is showed to be equivalent to maximising neutrality in physical space. The physics of epineutral dispersion is also reviewed and discussed. It is argued, in particular, that epineutral dispersion is best understood as the aggregate effect of many individual non-neutral stirring events (being understood here as adiabatic and isohaline events with non-zero buoyancy, so that it is only the net displacement aggregated over many events that is approximately neutral. This new view resolves an apparent paradox between the focus in neutral density theory on zero-buoyancy motions and the overwhelming evidence that lateral dispersion in the ocean is primarily caused by non-zero buoyancy processes such as tides, residual currents and sheared internal waves. The efficiency by which a physical process contributes to lateral dispersion can be characterised by its energy signature, with those processes releasing available potential energy (negative energy cost being more efficient than purely neutral processes with zero energy cost. The latter mechanism occurs in the wedge of instability, and its source of energy is the coupling between baroclinicity, thermobaricity, and density compensated temperature/salinity anomalies. Such a mechanism, which can only exist in a salty ocean, is speculated to be important for dissipating spiciness anomalies and neutral helicity. The paper also discusses potential

  12. Genome-wide scan identifies variant in TNFSF13 associated with serum IgM in a healthy Chinese male population.

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    Ming Yang

    Full Text Available IgM provides a first line of defense during microbial infections. Serum IgM levels are detected routinely in clinical practice. And IgM is a genetically complex trait. We conducted a two-stage genome-wide association study (GWAS to identify genetic variants affecting serum IgM levels in a Chinese population of 3495, including 1999 unrelated subjects in the first stage and 1496 independent individuals in the second stage. Our data show that a common single nucleotide polymorphism (SNP, rs11552708 located in the TNFSF13 gene was significantly associated with IgM levels (p = 5.00×10(-7 in first stage, p = 1.34×10(-3 in second stage, and p = 4.22×10(-9 when combined. Besides, smoking was identified to be associated with IgM levels in both stages (P0.05. It is suggested that TNFSF13 may be a susceptibility gene affecting serum IgM levels in Chinese male population.

  13. Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies.

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    Laura E McCoy

    2015-08-01

    Full Text Available The broadly neutralizing HIV monoclonal antibodies (bnMAbs PG9, PG16, PGT151, and PGT152 have been shown earlier to occasionally display an unusual virus neutralization profile with a non-sigmoidal slope and a plateau at <100% neutralization. In the current study, we were interested in determining the extent of non-sigmoidal slopes and plateaus at <100% for HIV bnMAbs more generally. Using both a 278 panel of pseudoviruses in a CD4 T-cell (U87.CCR5.CXCR4 assay and a panel of 117 viruses in the TZM-bl assay, we found that bnMAbs targeting many neutralizing epitopes of the spike had neutralization profiles for at least one virus that plateaued at <90%. Across both panels the bnMAbs targeting the V2 apex of Env and gp41 were most likely to show neutralization curves that plateaued <100%. Conversely, bnMAbs targeting the high-mannose patch epitopes were less likely to show such behavior. Two CD4 binding site (CD4bs Abs also showed this behavior relatively infrequently. The phenomenon of incomplete neutralization was also observed in a large peripheral blood mononuclear cells (PBMC-grown molecular virus clone panel derived from patient viral swarms. In addition, five bnMAbs were compared against an 18-virus panel of molecular clones produced in 293T cells and PBMCs and assayed in TZM-bl cells. Examples of plateaus <90% were seen with both types of virus production with no consistent patterns observed. In conclusion, incomplete neutralization and non-sigmoidal neutralization curves are possible for all HIV bnMAbs against a wide range of viruses produced and assayed in both cell lines and primary cells with implications for the use of antibodies in therapy and as tools for vaccine design.

  14. Neutral theory in community ecology

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    One of the central goals of community ecology is to understand the forces that maintain species diversity within communities. The traditional niche-assembly theory asserts that species live together in a community only when they differ from one another in resource uses. But this theory has some difficulties in explaining the diversity often observed in specie-rich communities such as tropical forests. As an alternative to the niche theory, Hubbell and other ecologists introduced a neutral model. Hubbell argues that the number of species in a community is controlled by species extinction and immigration or speciation of new species. Assuming that all individuals of all species in a trophically similar com-munity are ecologically equivalent, Hubbell's neutral theory predicts two important statistical distributions. One is the asymptotic log-series distribution for the metacommunities under point mutation speciation, and the other is the zero-sum multinomial distribution for both local communities under dispersal limitation and metacommunities under random fission speciation. Unlike the niche-assembly theory, the neutral theory takes similarity in species and individuals as a starting point for investigating species diversity. Based on the fundamental processes of birth, death, dispersal and spe-ciation, the neutral theory provided the first mechanistic explanation of species abundance distribution commonly observed in natural communities. Since the publication of the neutral theory, there has been much discussion about it, pro and con. In this paper, we summarize recent progress in the assumption, prediction and speciation mode of the neutral theory, including progress in the theory itself, tests about the assumption of the theory, prediction and speciation mode at the metacommunity level. We also suggest that the most important task in the future is to bridge the niche-assembly theory and the neutral theory, and to add species differences to the neutral theory and

  15. Natural IgM and TLR Agonists Switch Murine Splenic Pan-B to “Regulatory” Cells That Suppress Ischemia-Induced Innate Inflammation via Regulating NKT-1 Cells

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    Peter I. Lobo

    2017-08-01

    Full Text Available Natural IgM anti-leukocyte autoantibodies (IgM-ALAs inhibit inflammation by several mechanisms. Here, we show that pan-B cells and bone marrow-derived dendritic cells (BMDCs are switched to regulatory cells when pretreated ex vivo with IgM. B cells are also switched to regulatory cells when pretreated ex vivo with CpG but not with LPS. Pre-emptive infusion of such ex vivo induced regulatory cells protects C57BL/6 mice from ischemia-induced acute kidney injury (AKI via regulation of in vivo NKT-1 cells, which normally amplify the innate inflammatory response to DAMPS released after reperfusion of the ischemic kidney. Such ex vivo induced regulatory pan-B cells and BMDC express low CD1d and inhibit inflammation by regulating in vivo NKT-1 in the context of low-lipid antigen presentation and by a mechanism that requires costimulatory molecules, CD1d, PDL1/PD1, and IL10. Second, LPS and CpG have opposite effects on induction of regulatory activity in BMDC and B cells. LPS enhances regulatory activity of IgM-pretreated BMDC but negates the IgM-induced regulatory activity in B cells, while CpG, with or without IgM pretreatment, induces regulatory activity in B cells but not in BMDC. Differences in the response of pan-B and dendritic cells to LPS and CpG, especially in the presence of IgM-ALA, may have relevance during infections and inflammatory disorders where there is an increased IgM-ALA and release of TLRs 4 and 9 ligands. Ex vivo induced regulatory pan-B cells could have therapeutic relevance as these easily available cells can be pre-emptively infused to prevent AKI that can occur during open heart surgery or in transplant recipients receiving deceased donor organs.

  16. Natural IgM and TLR Agonists Switch Murine Splenic Pan-B to “Regulatory” Cells That Suppress Ischemia-Induced Innate Inflammation via Regulating NKT-1 Cells

    Science.gov (United States)

    Lobo, Peter I.; Schlegel, Kailo H.; Bajwa, Amandeep; Huang, Liping; Okusa, Mark D.

    2017-01-01

    Natural IgM anti-leukocyte autoantibodies (IgM-ALAs) inhibit inflammation by several mechanisms. Here, we show that pan-B cells and bone marrow-derived dendritic cells (BMDCs) are switched to regulatory cells when pretreated ex vivo with IgM. B cells are also switched to regulatory cells when pretreated ex vivo with CpG but not with LPS. Pre-emptive infusion of such ex vivo induced regulatory cells protects C57BL/6 mice from ischemia-induced acute kidney injury (AKI) via regulation of in vivo NKT-1 cells, which normally amplify the innate inflammatory response to DAMPS released after reperfusion of the ischemic kidney. Such ex vivo induced regulatory pan-B cells and BMDC express low CD1d and inhibit inflammation by regulating in vivo NKT-1 in the context of low-lipid antigen presentation and by a mechanism that requires costimulatory molecules, CD1d, PDL1/PD1, and IL10. Second, LPS and CpG have opposite effects on induction of regulatory activity in BMDC and B cells. LPS enhances regulatory activity of IgM-pretreated BMDC but negates the IgM-induced regulatory activity in B cells, while CpG, with or without IgM pretreatment, induces regulatory activity in B cells but not in BMDC. Differences in the response of pan-B and dendritic cells to LPS and CpG, especially in the presence of IgM-ALA, may have relevance during infections and inflammatory disorders where there is an increased IgM-ALA and release of TLRs 4 and 9 ligands. Ex vivo induced regulatory pan-B cells could have therapeutic relevance as these easily available cells can be pre-emptively infused to prevent AKI that can occur during open heart surgery or in transplant recipients receiving deceased donor organs. PMID:28878768

  17. Vendor neutral archive in PACS

    Directory of Open Access Journals (Sweden)

    Tapesh Kumar Agarwal

    2012-01-01

    Full Text Available An archive is a location containing a collection of records, documents, or other materials of historical importance. An integral part of Picture Archiving and Communication System (PACS is archiving. When a hospital needs to migrate a PACS vendor, the complete earlier data need to be migrated in the format of the newly procured PACS. It is both time and money consuming. To address this issue, the new concept of vendor neutral archive (VNA has emerged. A VNA simply decouples the PACS and workstations at the archival layer. This is achieved by developing an application engine that receives, integrates, and transmits the data using the different syntax of a Digital Imaging and Communication in Medicine (DICOM format. Transferring the data belonging to the old PACS to a new one is performed by a process called migration of data. In VNA, a number of different data migration techniques are available to facilitate transfer from the old PACS to the new one, the choice depending on the speed of migration and the importance of data. The techniques include simple DICOM migration, prefetch-based DICOM migration, medium migration, and the expensive non-DICOM migration. "Vendor neutral" may not be a suitable term, and "architecture neutral," "PACS neutral," "content neutral," or "third-party neutral" are probably better and preferred terms. Notwithstanding this, the VNA acronym has come to stay in both the medical IT user terminology and in vendor nomenclature, and radiologists need to be aware of its impact in PACS across the globe.

  18. Comparison of automated chemiluminescence immunoassays with capture enzyme immunoassays for the detection of measles and mumps IgM antibodies in serum.

    Science.gov (United States)

    Haywood, Becky; Patel, Mauli; Hurday, Samantha; Copping, Ruth; Webster, Daniel; Irish, Dianne; Haque, Tanzina

    2014-02-01

    Outbreaks of measles and mumps occur regularly in the UK. Rapid diagnosis of acute infection is important for both infection control and epidemiological purposes. The objective of this study was to compare the performance of an automated platform (DiaSorin Liaison(®), Saluggia, Italy) with a manual capture enzyme immunoassay (EIA; Microimmune, Hounslow, UK) for the detection of measles and mumps IgM antibodies in serum from symptomatic individuals. Ninety sera tested previously for measles (n=50) and mumps (n=40) IgM using the manual EIA were tested retrospectively using the DiaSorin Liaison(®) and the results compared. Sensitivity, specificity, inter-assay variability and intra-assay variability of the Liaison(®) assays were calculated. Sensitivity and specificity of the Liaison(®) assay for measles IgM were 92% and 100% respectively, with inter-assay variation of 14.1% and intra-assay variation of 12.5%. The sensitivity and specificity of the mumps IgM Liaison(®) assay were 88% and 95% respectively, with an inter-assay and intra-assay variation of 13.9% and 5.3% respectively. Both the measles and mumps IgM Liaison(®) assays gave fewer equivocal results than the EIA. Neither Liaison(®) IgM assay showed any cross-reactivity with sera positive against other viruses, however the measles IgM EIA cross-reacted with parvovirus IgM. The automated Liaison(®) assays are more specific, cheaper and less labour-intensive compared to the manual EIA. The Liaison(®) assays benefit from reduced number of equivocal results compared to the EIA for both measles and mumps IgM. This allows clinical decisions to be made accurately and in a timely manner.

  19. Clinical evaluation of new automated cytomegalovirus IgM and IgG assays for the Elecsys(®) analyser platform.

    Science.gov (United States)

    Revello, M G; Vauloup-Fellous, C; Grangeot-Keros, L; van Helden, J; Dickstein, Y; Lipkin, I; Mühlbacher, A; Lazzarotto, T

    2012-12-01

    Cytomegalovirus (CMV) is a leading cause of physical and neurological abnormalities in newborns. Hence, the diagnosis of CMV infection in pregnant women is necessary in order to allow appropriate management of their pregnancy. New assays have been developed for the Roche Elecsys® immunoassay platform that detect CMV-specific immunoglobulin (Ig)M and IgG, with the IgM assay designed to target IgM produced at the start of infection rather than IgM persisting later in infection. This study aimed to evaluate the performance of the new assays compared with other commercial kits widely distributed in laboratories. The performance of the Elecsys and comparator CMV IgM and IgG assays was assessed using 967 preselected patient samples characterised by CMV infection status, as well as being compared using 1,668 unselected clinical samples. The Elecsys CMV IgM and IgG assays performed consistently with comparator assays using the preselected samples. The Elecsys CMV IgM assay showed improved sensitivity compared with the Enzygnost® assay in primary infection (91.2 % vs. 79.4 %) and improved specificity over the Architect® assay in potentially cross-reacting samples (94.1 % vs. 82.4 %). The Elecsys IgM assay reported fewer positive results in the later stages of CMV infection compared with ETI-CYTOK-M ELISA, while the Elecsys IgG assay reported slightly fewer negative results in the early stages of infection compared with ETI-CYTOK-G ELISA. There was good agreement between Elecsys and comparator assays using unselected clinical samples (range 90.4-99.4 %). The Elecsys CMV IgM and IgG assays compare well with routinely used assays and are suitable for clinical use.

  20. Diagnosis of Helicobacter pylori Infection Using ELISA for Detection of Serum IgM, IgG and IgA Antibodies

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    MH K. Ansari

    2007-06-01

    Full Text Available Background: Helicobacter pylori is gram negative bacteria and is the etiologic agent of some gastrointestinal disease are such as chronic gastritis, gastric ulcers, lymphoma and aden carcinoma. Multiple invasive and noninvasive methods for detection of this infection are available, and among non invasive methods diagnostic value of specific IgM, IgG and IgA by ELISAis one of the best methods. The aim of this study to detect H. pylori antibodies for IgM, IgG and IgA by ELISA method. Methods: Blood samples From 131 referred patients (78 female and 53 male for detection of H.pylori was taken and serum separated for detection of IgM, IgG and IgA antibodies. IgG assessed by EIU units (42 was Positive .Also for IgM and IgA antibodies reported by U/ml unit (12 was Positive. Results: 131 Samples were tested for H. pylori IgM, IgG and IgA antibodies and showed 27.47%, 42% and 25.19% positive for IgM, IgG and IgA antibodies respectively. Age group 20-40 years old for IgM, IgG and IgA antibodies 23.3% and 28.3% and 16.7% positive respectively and for 41-80 years old IgM, IgG and IgA antibodies were 31%, 53.5% and 32%, respectively. The above data showing infection is higher at 41- 80 years old patients. Conclusion: The simple method for detection of H. pylori antibodies are available commercially and have sensitivity and specificity for H. pylori diseases. IgG, IgM and IgA have diagnostic importance, therefore regarding acceptable sensitivity and specificity, ease of work with ELISA, being economical and non invasive, it can be employed in diagnosis of H. pylori infections.

  1. The sensitivity and specificity of Lassa virus IgM by ELISA as screening tool at early phase of Lassa fever infection

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    Titus S Ibekwe

    2012-01-01

    Full Text Available Background: Early diagnosis, prompt treatment, and disease containment are vital measures in the management of Lassa fever (LF, a lethal and contagious arenaviral hemorrhagic disease prevalent in West Africa. Lassa Virus (LAV-specific Reverse Transcriptase Polymerase Chain Reaction (RT-PCR test, the gold standard for diagnosis, is unavailable in most centers. Serologic detection of LAV IgM is a more accessible tool and this work was to investigate its adequacy as an early marker for LF. Patients and Methods: A prospective case-control study conducted July 2007-March 2011 in a tertiary referral health center in Nigeria. Blood samples for test and control were evaluated for Lassa specific antigens and IgM using RT-PCR (primers S36+ and LVS 339 and indirect ELISA (Lassa Nucleo-protein (NP-Antigen respectively. RT-PCR outcome was used as standard to test for the sensitivity and specificity of IgM. Results: Of the 37 confirmed cases of LF infection by RT-PCR, 21 (57% were IgM positive. Amongst the 35 confirmed negative cases (control group, eight were IgM positive. The diagnostic sensitivity and specificity of the IgM assay were 57% and 77% respectively. The negative and positive predictive values of the IgM serological assay were 63% and 72%, respectively, while the efficiency of the test was 67%. Conclusion: The specificity and sensitivity of IgM as a screening tool for early detection of LF appear weak and, hence, the need for a reliable LF "rapid screening kit" since RT-PCR is unavailable in most centers. In the interim, "high clinical index of suspicion," irrespective of IgM status, requires urgent referral to confirmatory centers.

  2. A Comparative Study on Sensitivity and Specificity of Conventional and Unconventional IgG and IgM Assays for Diagnosis of Toxoplasmosis

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    MJ Gharavi

    2008-12-01

    Full Text Available "nBackground: Toxoplasmosis is a zoonotic disease with widespread distribution throughout the world. It is caused by the pro­tozoan parasite Toxoplasma gondii. As laboratory diagnosis of toxoplasmosis is not straightforward, this study was aimed to compare the sensitivity and specificity of conventional and unconventional methods of diagnosis based on the meas­urement of IgM and IgG for determination of the best method."nMethods: One hundred suspected cases of toxoplasmosis referred to two laboratories in Tehran and Karaj were entered into this comparative analytical study. The serum specimens of these cases were tested with ELISA, IFA, chemiluminescence (CLIA and ELFA for presence of IgG and IgM."nResults: When compared with the ELFA IgG method, the CLIA IgG had the highest sensitivity, specificity, and positive and negative predictive values (100%. In comparison with ELFA IgM method, CLIA IgM and ELISA IgM had the same sen­sitivity (92%, but the sensitivity of ELISA IgM (100% was higher than CLIA IgM (97.3%. The positive and negative pre­dictive values of ELISA IgM were 100% and 97.4%, respectively and those of CLIA IgM were 96% and 98%, in that or­der."nConclusion: Although, the reliability of the compared methods are close to each other, the automatic methods (CLIA, ELFA are preferred because of high reproducibility, less personnel costs, shorter test time and etc. Therefore, we recom­mend application of these methods for diagnosing of toxoplasmosis and re-emphasize that these are the most suitable tests for measurement of toxoplasma IgM levels.

  3. Cosmic Galaxy-IGM HI Relation at z ∼ 2–3 Probed in the COSMOS/UltraVISTA 1.6 Deg2 Field

    Science.gov (United States)

    Mukae, Shiro; Ouchi, Masami; Kakiichi, Koki; Suzuki, Nao; Ono, Yoshiaki; Cai, Zheng; Inoue, Akio K.; Chiang, Yi-Kuan; Shibuya, Takatoshi; Matsuda, Yuichi

    2017-02-01

    We present spatial correlations of galaxies and IGM neutral hydrogen H i in the COSMOS/UltraVISTA 1.62 deg2 field. Our data consist of 13,415 photo-z galaxies at z ∼ 2–3 with {K}s whose negative values correspond to the strong Lyα forest absorption lines. We identify weak evidence of an anti-correlation between δ gal and {δ } with a Spearman’s rank correlation coefficient of ‑0.39 suggesting that the galaxy overdensities and the Lyα forest absorption lines positively correlate in space at the ∼90% confidence level. This positive correlation indicates that high-z galaxies exist around an excess of H i gas in the Lyα forest. We find four cosmic volumes, dubbed A obs, B obs, C obs, and D obs, that have extremely large (small) values of δ gal ≃ 0.8 (‑1) and {δ } ≃ 0.1(-0.4), three of which, B obs–D obs, significantly depart from the δ gal–{δ } correlation, and weaken the correlation signal. We perform cosmological hydrodynamical simulations and compare with our observational results. Our simulations reproduce the δ gal–{δ } correlation, agreeing with the observational results. Moreover, our simulations have model counterparts of A obs–D obs, and suggest that the observations pinpoint, by chance, a galaxy overdensity like a proto-cluster, gas filaments lying on the quasar sightline, a large void, and orthogonal low-density filaments. Our simulations indicate that the significant departures of B obs–D obs are produced by the filamentary large-scale structures and the observation sightline effects.

  4. Deterioration of lung function is associated with presence of IgM rheumatoid factor and smoking in patients with systemic sclerosis

    DEFF Research Database (Denmark)

    Broholm, Berit; Ullman, Susanne; Halberg, Poul

    2008-01-01

    Smoking is a known risk factor for the development of several lung diseases, autoimmune diseases, and IgM rheumatoid factor (RF) in nonrheumatic persons. In patients with rheumatoid arthritis and IgM RF the diffusion capacity is decreased in smokers but not in nonsmokers. In the present study......M RF was found only in smokers or previous smokers, P = 0.007 and P = 0.01, respectively. These findings were confirmed by means of multiple regression analyses. The presence of IgM RF in smoking SSc patients is associated with deteriorating lung function. Whether this is a causal association...

  5. Retrospective diagnosis of Q fever in a country abattoir by the use of specific IgM globulin estimations

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, A.M.; Hunt, J.G.

    1981-10-03

    Twenty-two cases of pyrexial illness which occurred amongst workers in a country abattoir were investigated retrospectively for Q fever, brucellosis, and leptospirosis. In 18, the illness was shown to be Q fever. No diagnoses were established for the other four. The demonstration of circulating Q-fever-specific IgM globulin was instrumental in establishing the diagnosis in many of the cases.

  6. IGM Constraints from the SDSS-III/BOSS DR9 Ly-alpha Forest Flux Probability Distribution Function

    CERN Document Server

    Lee, Khee-Gan; Spergel, David N; Weinberg, David H; Hogg, David W; Viel, Matteo; Bolton, James S; Bailey, Stephen; Pieri, Matthew M; Carithers, William; Schlegel, David J; Lundgren, Britt; Palanque-Delabrouille, Nathalie; Suzuki, Nao; Schneider, Donald P; Yeche, Christophe

    2014-01-01

    The Ly$\\alpha$ forest flux probability distribution function (PDF) is an established probe of the intergalactic medium (IGM) astrophysics, especially the temperature-density relationship of the IGM. We measure the flux PDF from 3393 Baryon Oscillations Spectroscopic Survey (BOSS) quasars from SDSS Data Release 9, and compare with mock spectra that include careful modeling of the noise, continuum, and astrophysical uncertainties. The BOSS flux PDFs, measured at $\\langle z \\rangle = [2.3,2.6,3.0]$, are compared with PDFs created from mock spectra drawn from a suite of hydrodynamical simulations that sample the IGM temperature-density relationship, $\\gamma$, and temperature at mean-density, $T_0$, where $T(\\Delta) = T_0 \\Delta^{\\gamma-1}$. We find that a significant population of partial Lyman-limit systems with a column-density distribution slope of $\\beta_\\mathrm{pLLS} \\sim -2$ are required to explain the data at the low-flux end of flux PDF, while uncertainties in the mean \\lya\\ forest transmission affect the...

  7. [Rheumatoid factor activity as a disturbing factor in the serological diagnosis of specific IgM antibodies].

    Science.gov (United States)

    Lindenschmidt, E G

    1984-04-01

    Rheumatoid factors (RF) are autoantibodies mainly directed against autologous IgG. They belong at most to the IgM class antibodies. It is demonstrated at groups with unsolved hepatitis B, rubella, syphilis and toxoplasmose infection that RF do occur not rarely at these patients even without rheumatoid arthritis. This is probably due to stimulation by antigen-IgG-complexes. During serologic detection of specific IgM antibodies they present an antigen independent mu-specificity. So the test for specific IgM might even loose its diagnostic and possibly therapy indicating value. It is shown how the disturbance by RF can be calculated after adsorption with aggregated IgG. Also RF can be titrated by an enzyme immunoassay (ELISA). With IgG coated latex particles RF can be eliminated prior to the IgM-test. Solid phase techniques which are applied with enzyme-coupled antigen instead of marked anti-IgM cannot be disturbed by RF significantly.

  8. Acne conglobata in a long-term survivor with trisomy 13, accompanied by selective IgM deficiency.

    Science.gov (United States)

    Inoue, Chiyoko N; Tanaka, Yoshiko; Tabata, Nobuko

    2017-05-07

    Trisomy 13 (T13) is a congenital chromosomal disorder that is usually fatal within 2 years of birth, and only a few patients have been reported to reach adolescence. Here, we report a male long-term survivor of T13, currently 15 years of age, with a several-year history of extensive acne conglobata (AC) with abscesses on the face and neck. Methicillin-resistant Staphylococcus aureus was consistently isolated from the pustular lesions. Serum IgM levels were extremely low at 10 mg/dl. There were no abnormalities in neutrophil and total B cell number, or in serum IgA and IgG levels. Increased CD8+ T cell counts and inversion of the CD4/CD8 ratio were observed repeatedly. The patient's clinical features and laboratory data support a diagnosis of selective IgM deficiency (SIgMD) with concurrent AC. Immunoglobulin replacement therapy elevated serum IgM levels to the normal range and reduced the severity of AC. We suggest that T13 may represent a syndromic disorder associated with multiple organ malformation and a risk of developing immunodeficiency involving SIgMD. Because pediatric SIgMD is rare and an immunological abnormality in T13 patients has not previously been reported, we describe the patient's clinical course. © 2017 Wiley Periodicals, Inc.

  9. Novel B cell population producing functional IgG in the absence of membrane IgM expression.

    Science.gov (United States)

    Orinska, Zane; Osiak, Anna; Löhler, Jürgen; Bulanova, Elena; Budagian, Vadim; Horak, Ivan; Bulfone-Paus, Silvia

    2002-12-01

    Surface expression of IgM is a characteristic feature of the development of most B cells. Only pre-B cells bearing functional IgM heavy chains mu chains) are selected for clonal expansion and differentiation. Cells lacking mu chains are normally eliminated. muMT mice carrying a deletion of the first exon coding for the transmembrane domain of the immunoglobulin mu chain gene were described as mice deficient for mature B cells, plasma cells and immunoglobulins in serum. In this study, we describe in muMT/BALB/c mice the presence of a novel B cell population, producing IgG, IgA and IgE in the absence of IgM membrane expression. Moreover, this small population of B cells is able to recognize antigens and to differentiate into plasma cells. These "non-conventional" mu(- / -) B cells produce functional immunoglobulins after immunization, undergo germinal center reactions, and maintain B cell memory. Our findings support the concept, that a small percentage of mu -non-expressing pre-B cells can escape elimination, switch to downstream immunoglobulin heavy chains and respond to antigens. It remains an open question how the reactivity of these B cells is regulated and in which extent such B cells play a role in physiological and pathological processes such as autoantibody production and autoimmunity.

  10. Comparative study of immunochromatographic assay (IgM) and widal test for early diagnosis of typhoid fever.

    Science.gov (United States)

    Sultana, S; Hossain, M A; Alam, M A; Paul, S K; Kabir, M R; Hoque, S M; Yesmin, T; Habiba, U; Sarkar, S R; Maruf, M A; Halim, P I; Hoque, M R

    2012-10-01

    Typhoid fever is a severe systemic infection endemic in many developing countries, including Bangladesh. Present study evaluated immunochromatographic test (ICT) and Widal test in the early diagnosis of typhoid fever cases. The study was carried out in the department of Microbiology, Mymensingh Medical College, Mymensingh between July, 2010 and June, 2011, including 200 individuals of different age and sex. Of them, 150 were clinically suspected cases of typhoid fever and 50 age-sex matched controls. Among 150 blood samples from the suspected cases 106(70.7%) were positive for IgM of Salmonella typhi by ICT and 67(44.7%) were positive by Widal test. Whereas, among the 50 controls 4(8%) were positive by ICT and 6(12%) were positive by Widal test. The sensitivity, specificity, positive and negative predictive value of the ICT was found as 83.3%, 92.00%, 91.9% and 83.6% respectively. On the other hand corresponding values for Widal test were of 44.4%, 88%, 80% and 59.5% respectively. Thus, The ICT (IgM) is better alternative to Widal test for early and accurate diagnosis of typhoid fever. The ICT (IgM) is rapid, easy to perform, applicable for field use and highly sensitive and specific for detection of antibodies in patients with typhoid fever.

  11. Fuzzy Controller based Neutral Current Harmonic Suppression in Distribution System

    Directory of Open Access Journals (Sweden)

    T.Guna Sekar

    2013-10-01

    Full Text Available Recent surveys of three-phase four-wire electric systems, buildings and industrial plants with computers and non-linear loads shows the excessive currents in the neutral conductor. This is mainly due to unbalancing system and non-linear loads. Third order harmonics are much dominant in the neutral conductor due to the presence of zero sequence components. In response to this concern, this paper presents a concept of series active filter scheme to suppress the neutral current harmonics to reduce the burden of the secondary of the distribution transformer. In this scheme, the series active filteris connected in series with the neutral conductor to eliminate the zero sequence components in the neutral conductor. In this paper, Fuzzy based controller is used to extract the harmonic component in the neutral conductor. The proposed method improves the overall performance of the system and eliminates the burden of the neutral conductor. To validate the proposed simulation results, a scale-down prototype experimental model is developed.

  12. ABO (histo) blood group phenotype development and human reproduction as they relate to ancestral IgM formation: A hypothesis.

    Science.gov (United States)

    Arend, Peter

    2016-01-01

    The formation of a histo (blood) group) ABO phenotype and the exclusion of an autoreactive IgM or isoagglutinin activity arise apparently in identical glycosylation of complementary domains on cell surfaces and plasma proteins. The fundamental O-glycan emptiness of the circulating IgM, which during the neonatal amino acid sequencing of the variable regions is exerting germline-specific O-GalNAc glycan-reactive serine/threonine residues that in the plasma of the adult human blood group O individuals apparently remain associated with the open glycosidic sites on the ABOH convertible red cell surface, must raise suggestions on a transient expression of developmental glycans, which have been "lost" over the course of maturation. In fact, while the mammalian non-somatic, embryogenic stem cell (ESC)- germ cell (GC) transformation is characterized by a transient and genetically as-yet-undefined trans-species-functional O-GalNAc glycan expression, in the C57BL/10 mouse such expression was potentially identified in growth-dependent, blood group A-like GalNAc glycan-bearing, ovarian glycolipids complementary with the syngeneic anti-A reactive IgM, which does not appear in early ovariectomized animals. This non-somatically encoded, polyreactive, ancestral IgM molecule has not undergone clonal selection and does primarily not differentiate between self and non-self and might, due to amino acid hydroxyl groups, highly suggest substrate competition with subsequent O-glycosylations in ongoing ESC-GC transformations and affecting GC maturation. However, the membrane-bound somatic N/O-glycotransferases, which initiate, after formation of the zygote, the complex construction of the human ABO phenotypes in the trans cisternae of the Golgi apparatus, are associated and/or completed with soluble enzyme versions exerting identical specificities in plasma and likely competing vice versa by glycosylation of neonatal IgM amino acids, where they suggest to accomplish the clearance of anti

  13. Cross-Reactivity of Rapid Salmonella Typhi IgM Immunoassay in Dengue Fever Without Co-Existing Infection.

    Science.gov (United States)

    Bhatti, Adnan Bashir; Ali, Farhan; Satti, Siddique Akbar

    2015-12-04

    Dengue fever is endemic in developing nations worldwide with as many as 500,000 annual cases of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). A prompt and accurate diagnosis early in the disease course is essential for prompt identification and treatment of severe complications of the dengue virus infection (DVI). We identified cross-reactivity of a rapid IgM test for typhoid fever in patients with febrile illnesses that were determined to be due to dengue virus. All patients with documented DVI during a recent epidemic in Pakistan also underwent diagnostic testing for Salmonella enterica serovar Typhi. The diagnosis of DVI was made based on clinical findings and the positive results for dengue non-structural protein 1 antigen (NS1Ag) and/or dengue IgM antibody (anti-D IgM) during the acute phase of febrile illness. Patients with positive test results for Salmonella typhi (S. Typhi) IgM also had their blood cultures done. In the group of 322 patients with clinical and serological evidence of DVI, 107 also tested positive for S. Typhi IgM. Blood cultures were negative for S. Typhi bacteria in all patients. Principal disease features included fever, headache, myalgia, retro-orbital pain, and a rash accompanied by thrombocytopenia and leukopenia. Comparisons of clinical and routine laboratory findings between the S. Typhi-positive and negative groups showed no significant differences. Patients testing positive for both NS1Ag and anti-D IgM were significantly more likely to test positive for S. Typhi IgM, even in the absence of typhoid fever. No routine antibiotics were used and all patients survived. One-third of a large group of patients with primary DVI also demonstrated false positive results for typhoid fever. Cross-reactivity of a rapid immunoassay for typhoid fever has not been previously reported in DVI or any other flavivirus infections. Until these findings can be further evaluated, clinicians should be cautious in

  14. High seroprevalence of Mycoplasma pneumoniae IgM in acute Q fever by enzyme-linked immunosorbent assay (ELISA.

    Directory of Open Access Journals (Sweden)

    Chung-Hsu Lai

    Full Text Available Q fever is serologically cross-reactive with other intracellular microorganisms. However, studies of the serological status of Mycoplasma pneumoniae and Chlamydophila pneumoniae during Q fever are rare. We conducted a retrospective serological study of M. pneumoniae and C. pneumoniae by enzyme-linked immunosorbent assay (ELISA, a method widely used in clinical practice, in 102 cases of acute Q fever, 39 cases of scrub typhus, and 14 cases of murine typhus. The seropositive (57.8%, 7.7%, and 0%, p<0.001 and seroconversion rates (50.6%, 8.8%, and 0%, p<0.001 of M. pneumoniae IgM, but not M. pneumoniae IgG and C. pneumoniae IgG/IgM, in acute Q fever were significantly higher than in scrub typhus and murine typhus. Another ELISA kit also revealed a high seropositivity (49.5% and seroconversion rate (33.3% of M. pneumoniae IgM in acute Q fever. The temporal and age distributions of patients with positive M. pneumoniae IgM were not typical of M. pneumoniae pneumonia. Comparing acute Q fever patients who were positive for M. pneumoniae IgM (59 cases with those who were negative (43 cases, the demographic characteristics and underlying diseases were not different. In addition, the clinical manifestations associated with atypical pneumonia, including headache (71.2% vs. 81.4%, p=0.255, sore throat (8.5% vs. 16.3%, p=0.351, cough (35.6% vs. 23.3%, p=0.199, and chest x-ray suggesting pneumonia (19.3% vs. 9.5%, p=0.258, were unchanged between the two groups. Clinicians should be aware of the high seroprevalence of M. pneumoniae IgM in acute Q fever, particularly with ELISA kits, which can lead to misdiagnosis, overestimations of the prevalence of M. pneumoniae pneumonia, and underestimations of the true prevalence of Q fever pneumonia.

  15. Deterioration of lung function is associated with presence of IgM rheumatoid factor and smoking in patients with systemic sclerosis

    DEFF Research Database (Denmark)

    Broholm, B.; Ullman, S.; Halberg, P.

    2008-01-01

    of patients with systemic sclerosis (SSc) the influence of smoking and IgM RF on the lung function was calculated. One hundred fifty-five persons with SSc had vital capacity (VC) and diffusing capacity (DLco) measured at least twice with at least 1-year interval as percents of predicted values according......Smoking is a known risk factor for the development of several lung diseases, autoimmune diseases, and IgM rheumatoid factor (RF) in nonrheumatic persons. In patients with rheumatoid arthritis and IgM RF the diffusion capacity is decreased in smokers but not in nonsmokers. In the present study...... and whether the presence of IgM RF in smoking patients with SSc actually confers an increased risk of pulmonary damage remains to be determined Udgivelsesdato: 2008/8...

  16. Broadly neutralizing antibodies developed by an HIV-positive elite neutralizer exact a replication fitness cost on the contemporaneous virus.

    Science.gov (United States)

    Sather, D Noah; Carbonetti, Sara; Kehayia, Jenny; Kraft, Zane; Mikell, Iliyana; Scheid, Johannes F; Klein, Florian; Stamatatos, Leonidas

    2012-12-01

    Approximately 1% of those infected with HIV-1 develop broad and potent serum cross-neutralizing antibody activities. It is unknown whether or not the development of such immune responses affects the replication of the contemporaneous autologous virus. Here, we defined a pathway of autologous viral escape from contemporaneous potent and broad serum neutralizing antibodies developed by an elite HIV-1-positive (HIV-1(+)) neutralizer. These antibodies potently neutralize diverse isolates from different clades and target primarily the CD4-binding site (CD4-BS) of the viral envelope glycoprotein. Viral escape required mutations in the viral envelope glycoprotein which limited the accessibility of the CD4-binding site to the autologous broadly neutralizing anti-CD4-BS antibodies but which allowed the virus to infect cells by utilizing CD4 receptors on their surface. The acquisition of neutralization resistance, however, resulted in reduced cell entry potential and slower viral replication kinetics. Our results indicate that in vivo escape from autologous broadly neutralizing antibodies exacts fitness costs to HIV-1.

  17. Strain-specific V3 and CD4 binding site autologous HIV-1 neutralizing antibodies select neutralization-resistant viruses

    Science.gov (United States)

    Moody, M. Anthony; Gao, Feng; Gurley, Thaddeus C.; Amos, Joshua D.; Kumar, Amit; Hora, Bhavna; Marshall, Dawn J.; Whitesides, John F.; Xia, Shi-Mao; Parks, Robert; Lloyd, Krissey E.; Hwang, Kwan-Ki; Lu, Xiaozhi; Bonsignori, Mattia; Finzi, Andrés; Vandergrift, Nathan A.; Alam, S. Munir; Ferrari, Guido; Shen, Xiaoying; Tomaras, Georgia D.; Kamanga, Gift; Cohen, Myron S.; Sam, Noel E.; Kapiga, Saidi; Gray, Elin S.; Tumba, Nancy L.; Morris, Lynn; Zolla-Pazner, Susan; Gorny, Miroslaw K.; Mascola, John R.; Hahn, Beatrice; Shaw, George M.; Sodroski, Joseph G.; Liao, Hua-Xin; Montefiori, David C.; Hraber, Peter T.; Korber, Bette T.; Haynes, Barton F.

    2015-01-01

    Summary The third variable (V3) loop and the CD4 binding site (CD4bs) of the HIV-1 envelope are frequently targeted by neutralizing antibodies (nAbs) in infected individuals. In chronic infection, HIV-1 escape mutants repopulate the plasma, and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize, but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tier 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses. PMID:26355218

  18. Neutralizing Antibodies and Pathogenesis of Hepatitis C Virus Infection

    Directory of Open Access Journals (Sweden)

    Françoise Stoll-Keller

    2012-10-01

    Full Text Available Hepatitis C virus (HCV infection is a major cause of chronic liver disease worldwide. The interplay between the virus and host innate and adaptive immune responses determines the outcome of infection. There is increasing evidence that host neutralizing responses play a relevant role in the resulting pathogenesis. Furthermore, viral evasion from host neutralizing antibodies has been revealed to be an important contributor in leading both to viral persistence in acute liver graft infection following liver transplantation, and to chronic viral infection. The development of novel model systems to study HCV entry and neutralization has allowed a detailed understanding of the molecular mechanisms of virus-host interactions during antibody-mediated neutralization. The understanding of these mechanisms will ultimately contribute to the development of novel antiviral preventive strategies for liver graft infection and an urgently needed vaccine. This review summarizes recent concepts of the role of neutralizing antibodies in viral clearance and protection, and highlights consequences of viral escape from neutralizing antibodies in the pathogenesis of HCV infection.

  19. Neutral hydrogen in galactic fountains

    CERN Document Server

    Booth, C M

    2007-01-01

    Simulations of an isolated Milky Way-like galaxy, in which supernovae power a galactic fountain, reproduce the observed velocity and 21cm brightness statistics of galactic neutral hydrogen (HI). The simulated galaxy consists of a thin HI disk, similar in extent and brightness to that observed in the Milky Way, and extra-planar neutral gas at a range of velocities due to the galactic fountain. Mock observations of the neutral gas resemble the HI flux measurements from the Leiden-Argentine-Bonn (LAB) HI, survey, including a high-velocity tail which matches well with observations of high-velocity clouds. The simulated high-velocity clouds are typically found close to the galactic disk, with a typical line-of-sight distance of 13kpc from observers on the solar circle. The fountain efficiently cycles matter from the centre of the galaxy to its outskirts at a rate of around 0.5 M_sun/yr

  20. Neutral B meson flavor tagging

    Science.gov (United States)

    Wilson, Robert J.

    2001-07-01

    We present an investigation of the use of net charge and kaon identification to tag the flavor of neutral B mesons. The net charge of the neutral B meson decay products is zero if all charged particles are used and slightly non-zero if only undiscriminated hadronic final states are used. The net charge of the kaons alone correctly tags the identity of the neutral meson in at least a third of all decays. We have parametrized the particle identification capability of several techniques, such as dE/dx in time projection chambers, LEP/SLC ring-imaging chambers and an enhanced BaBar DIRC. Using these parametrisations we compare the relative tagging power of each technique to that of an ideal detector.

  1. Neutral B meson flavor tagging

    CERN Document Server

    Wilson, R J

    2001-01-01

    We present an investigation of the use of net charge and kaon identification to tag the flavor of neutral B mesons. The net charge of the neutral B meson decay products is zero if all charged particles are used and slightly non-zero if only undiscriminated hadronic final states are used. The net charge of the kaons alone correctly tags the identity of the neutral meson in at least a third of all decays. We have parametrized the particle identification capability of several techniques, such as dE/dx in time projection chambers, LEP/SLC ring-imaging chambers and an enhanced BaBar DIRC. Using these parametrisations we compare the relative tagging power of each technique to that of an ideal detector. (8 refs).

  2. VIMOS Ultra-Deep Survey (VUDS): IGM transmission towards galaxies with 2.5 < z < 5.5 and the colour selection of high-redshift galaxies

    Science.gov (United States)

    Thomas, R.; Le Fèvre, O.; Le Brun, V.; Cassata, P.; Garilli, B.; Lemaux, B. C.; Maccagni, D.; Pentericci, L.; Tasca, L. A. M.; Zamorani, G.; Zucca, E.; Amorin, R.; Bardelli, S.; Cassarà, L.; Castellano, M.; Cimatti, A.; Cucciati, O.; Durkalec, A.; Fontana, A.; Giavalisco, M.; Grazian, A.; Hathi, N. P.; Ilbert, O.; Paltani, S.; Pforr, J.; Ribeiro, B.; Schaerer, D.; Scodeggio, M.; Sommariva, V.; Talia, M.; Tresse, L.; Vanzella, E.; Vergani, D.; Capak, P.; Charlot, S.; Contini, T.; Cuby, J. G.; de la Torre, S.; Dunlop, J.; Fotopoulou, S.; Koekemoer, A.; López-Sanjuan, C.; Mellier, Y.; Salvato, M.; Scoville, N.; Taniguchi, Y.; Wang, P. W.

    2017-01-01

    The observed UV rest-frame spectra of distant galaxies are the result of their intrinsic emission combined with absorption along the line of sight produced by the inter-galactic medium (IGM). Here we analyse the evolution of the mean IGM transmission Tr(Lyα) and its dispersion along the line of sight for 2127 galaxies with 2.5 sight and found that the IGM transmission towards galaxies is in excellent agreement with quasar values up to redshift z 4. We found tentative evidence for a higher IGM transmission at z ≥ 4 compared to results from QSOs, but a degeneracy between dust extinction and IGM prevents us from firmly concluding whether the internal dust extinction for star-forming galaxies at z > 4 takes a mean value significantly in excess of E(B-V) > 0.15. Most importantly, we found a large dispersion of IGM transmission along the lines of sight towards distant galaxies with 68% of the distribution within 10 to 17% of the median value in δz = 0.5 bins, similar to what is found on the lines of sight towards QSOs. We demonstrate that taking this broad range of IGM transmission into account is important when selecting high-redshift galaxies based on their colour properties (e.g. LBG or photometric redshiftselection) because failing to do so causes a significant incompleteness in selecting high-redshift galaxy populations. We finally discuss the observed IGM properties and speculate that the broad range of observed transmissions might be the result of cosmic variance and clustering along lines of sight. This clearly shows that the sources that cause this extinction need to be more completely modelled. Based on data obtained with the European Southern Observatory Very Large Telescope, Paranal, Chile, under Large Program 185.A-0791.

  3. Anti Japanese encephalitis virus IgM positivity among patients with acute encephalitic syndrome admitted to different hospitals from all over Nepal

    Science.gov (United States)

    Bhattarai, Anupama; Nepal, Krishus; Adhikari, Sailaja; Sharma, Mukunda; Parajuli, Pramila

    2017-01-01

    The Japanese encephalitis virus (JEV) infection is one of the major public health problems in Nepal because of its increasing disease morbidity and mortality. The main purpose of this study was to determine the anti-JEV IgM positivity among acute encephalitis syndromic cases from all over Nepal. The present study was conducted at National Public Health Laboratory, Kathmandu, Nepal from April 2015 to October 2015. A total of 671 (418 CSF and 253 serum) samples were collected from 625 patients with acute encephalitic syndrome, admitted to different hospitals from all over Nepal. IgM antibody capture enzyme linked immunosorbent assay (ELISA) was used for the detection of anti-JEV IgM positive cases. The rate of anti-JEV IgM positivity was found to be 21.12%. The majority of positive cases (50%) were from the age group below 15 years, with the highest numbers of cases occurring in September (55.30%). Among all the anti-JEV IgM positive cases, higher numbers of cases were males. Geographically, the highest numbers of anti-JEV IgM positive cases were recorded from Terai region. Similarly, largest numbers of anti-JEV IgM positive cases were reported from Kailai district followed by those from Kanchanpur. However, anti-JEV IgM positive cases were also reported from hill districts. Continuation of active surveillance and vector control measures, proper management of diagnostic facilities and expanded program of immunization in JE endemic areas should be strongly emphasized to reduce the endemicity of the disease. PMID:28264024

  4. Pseudothrombocytopenia: a report of a new method to count platelets in a patient with EDTA- and temperature-independent antibodies of the IgM type.

    Science.gov (United States)

    van der Meer, W; Allebes, W; Simon, A; van Berkel, Y; de Keijzer, M H

    2002-10-01

    Pseudothrombocytopenia is usually associated with blood specimens anticoagulated with ethylenediamine tetraacetic acid (EDTA) or other anticoagulants. It may be caused by temperature-independent, EDTA-dependent antibodies of the immunoglobulin-M (IgM) type. Here a patient with EDTA-independent and temperature-independent pseudothrombocytopenia mediated by IgM or IgM-containing immune complex is reported, and a reliable method is described for a proper counting of platelets in such cases.

  5. Pregnancy Outcomes of Mothers with Detectable CMV-Specific IgM Antibodies: A Three-Year Review in a Large Irish Tertiary Referral Maternity Hospital

    Science.gov (United States)

    Drew, Richard J.; Stapleton, Patrick; Abu, Hala; Healy, Eibhlín; Ferguson, Wendy; De Gascun, Cillian; O'Gorman, Joanne; Eogan, Maeve

    2015-01-01

    A retrospective audit was performed for all obstetric patients who had positive CMV IgM results between January 2012 and December 2014 in the Rotunda Hospital, Ireland. In total, 622 CMV IgM positive tests were performed on samples from 572 patients. Thirty-seven patients had a positive CMV IgM result (5.9%) on the Architect system as part of the initial screening. Three patients were excluded as they were not obstetric patients. Of the 34 pregnant women with CMV IgM positive results on initial screening, 16 (47%) had CMV IgM positivity confirmed on the second platform (VIDAS) and 18 (53%) did not. In the 16 patients with confirmed positive CMV IgM results, four (25%) had acute infection, two (12.5%) had infection of uncertain timing, and ten (62.5%) had infection more than three months prior to sampling as determined by the CMV IgG avidity index. Two of the four neonates of women with low avidity IgG had CMV DNA detected in urine. Both these cases had severe neurological damage and the indication for testing their mothers was because the biparietal diameter (BPD) was less than the 5th centile at the routine 20-week gestation anomaly scan. PMID:26696757

  6. Shark immunity bites back: affinity maturation and memory response in the nurse shark, Ginglymostoma cirratum.

    Science.gov (United States)

    Dooley, Helen; Flajnik, Martin F

    2005-03-01

    The cartilaginous fish are the oldest phylogenetic group in which all of the molecular components of the adaptive immune system have been found. Although early studies clearly showed that sharks could produce an IgM-based response following immunization, evidence for memory, affinity maturation and roles for the other isotypes (notably IgNAR) in this group remained inconclusive. The data presented here illustrate that the nurse shark (Ginglymostoma cirratum) is able to produce not only an IgM response, but we also show for the first time a highly antigen-specific IgNAR response. Additionally, under appropriate conditions, a memory response for both isotypes can be elicited. Analysis of the response shows differential expression of pentameric and monomeric IgM. Pentameric IgM provides the 'first line of defense' through high-avidity, low-affinity interaction with antigen. In contrast, monomeric IgM and IgNAR seem responsible for the specific, antigen-driven response. We propose the presence of distinct lineages of B cells in sharks. As there is no conventional isotype switching, each lineage seems pre-determined to express a single isotype (IgM versus IgNAR). However, our data suggest that there may also be specific lineages for the different forms (pentameric versus monomeric) of the IgM isotype.

  7. Traps for neutral radioactive atoms

    CERN Document Server

    Sprouse, G D; Grossman, J S; Orozco, L A; Pearson, M R

    2002-01-01

    We describe several methods for efficiently injecting a small number of radioactive atoms into a laser trap. The characteristics of laser traps that make them desirable for physics experiments are discussed and several different experimental directions are described. We describe recent experiments with the alkali element Fr and point to future directions of the neutral atom trapping program.

  8. Neutral Models with Generalised Speciation

    NARCIS (Netherlands)

    Haegeman, Bart; Etienne, Rampal S.

    Hubbell's neutral theory claims that ecological patterns such as species abundance distributions can be explained by a stochastic model based on simple assumptions. One of these assumptions, the point mutation assumption, states that every individual has the same probability to speciate. Etienne et

  9. Validation of an ELISA for the concurrent detection of total antibodies (IgM and IgG to Rift Valley fever virus

    Directory of Open Access Journals (Sweden)

    Charlotte E. Ellis

    2014-02-01

    Full Text Available Rift Valley fever virus (RVFV infects humans and livestock, causing haemorrhaging andabortions in animals. Three major RVF epizootics have occurred in South Africa since the1950s and the outbreak in 2010 had a mortality rate of 10.7% in humans. Accurate and earlydetection is therefore essential for management of this zoonotic disease. Enzyme-linkedimmunosorbent assays (ELISAs have been developed for the detection of either IgM or IgGantibodies to RVFV in animal sera. In this study, data are presented on the validation of adouble-antigen ELISA for the simultaneous detection of both classes of antibodies to RVFV ina single test. ELISA plates were coated with a recombinant nucleoprotein. The nucleoprotein,conjugated to horseradish peroxidase, was used as the detecting reagent. A total of 534 serafrom sheep and cattle were used in the validation. The sheep sera were collected during a RVFpathogenesis study at the Agricultural Research Council (ARC – Onderstepoort VeterinaryInstitute and the cattle sera were collected during an outbreak of RVF in 2008 at the ARC –Animal Production Institute in Irene, Pretoria. The ELISA had a diagnostic sensitivity of 98.4%and a specificity of 100% when compared to a commercial cELISA. This convenient and fastassay is suitable for use in serological surveys or monitoring immune responses in vaccinatedanimals.

  10. Phenotypic modulation of chronic lymphocytic leukemia cells by phorbol ester: induction of IgM secretion and changes in the expression of B cell-associated surface antigens.

    Science.gov (United States)

    Gordon, J; Mellstedt, H; Aman, P; Biberfeld, P; Klein, G

    1984-01-01

    Freshly explanted neoplastic populations from 22 cases of phenotypically well-characterized chronic type B lymphocytic leukemia were studied for their capacity to respond to the phorbol ester TPA in vitro. In all but four cases the secretion of IgM was either induced or increased, often to a high level. In contrast, the export of free immunoglobulin (Ig) light chains, an almost consistent feature of the B lymphocytic leukemias, remained relatively constant after TPA treatment. Parallel changes in leukemic cell surface phenotype were probed with both "conventional" and monoclonal antibodies, revealing some modulation of markers in every case investigated. A diminution in the level of surface Ig (preferentially IgD) and the accumulation of cytoplasmic Ig observed after phorbol ester treatment were accompanied by a corresponding reduction or loss of the B1 antigen and usually of B2 when present. The most consistent change induced by TPA was the appearance of BB-1, a marker of activated B lymphocytes, which was rarely expressed on fresh leukemic cells. Another marker of activated lymphocytes, LB-1, was also often induced or increased in its expression after exposure of the cells to TPA. The magnitude of the TPA response appeared to relate to the stage of maturation arrest of the individual leukemic clones rather than to any clinical parameter explored. The significance of the findings to normal B cell differentiation and their potential clinical utility are discussed.

  11. IGM CONSTRAINTS FROM THE SDSS-III/BOSS DR9 Lyα FOREST TRANSMISSION PROBABILITY DISTRIBUTION FUNCTION

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Khee-Gan; Hennawi, Joseph F. [Max Planck Institute for Astronomy, Königstuhl 17, D-69117 Heidelberg (Germany); Spergel, David N. [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Weinberg, David H. [Department of Astronomy and Center for Cosmology and Astro-Particle Physics, Ohio State University, Columbus, OH 43210 (United States); Hogg, David W. [Center for Cosmology and Particle Physics, New York University, 4 Washington Place, Meyer Hall of Physics, New York, NY 10003 (United States); Viel, Matteo [INAF, Osservatorio Astronomico di Trieste, Via G. B. Tiepolo 11, I-34131 Trieste (Italy); Bolton, James S. [School of Physics and Astronomy, University of Nottingham, University Park, Nottingham NG7 2RD (United Kingdom); Bailey, Stephen; Carithers, William; Schlegel, David J. [E.O. Lawrence Berkeley National Lab, 1 Cyclotron Road, Berkeley, CA 94720 (United States); Pieri, Matthew M. [Institute of Cosmology and Gravitation, University of Portsmouth, Dennis Sciama Building, Portsmouth PO1 3FX (United Kingdom); Lundgren, Britt [Department of Astronomy, University of Wisconsin, Madison, WI 53706 (United States); Palanque-Delabrouille, Nathalie; Yèche, Christophe [CEA, Centre de Saclay, Irfu/SPP, F-91191 Gif-sur-Yvette (France); Suzuki, Nao [Kavli Institute for the Physics and Mathematics of the Universe (IPMU), The University of Tokyo, Kashiwano-ha 5-1-5, Kashiwa-shi, Chiba (Japan); Schneider, Donald P., E-mail: lee@mpia.de [Department of Astronomy and Astrophysics, The Pennsylvania State University, University Park, PA 16802 (United States)

    2015-02-01

    The Lyα forest transmission probability distribution function (PDF) is an established probe of the intergalactic medium (IGM) astrophysics, especially the temperature-density relationship of the IGM. We measure the transmission PDF from 3393 Baryon Oscillations Spectroscopic Survey (BOSS) quasars from Sloan Digital Sky Survey Data Release 9, and compare with mock spectra that include careful modeling of the noise, continuum, and astrophysical uncertainties. The BOSS transmission PDFs, measured at (z) = [2.3, 2.6, 3.0], are compared with PDFs created from mock spectra drawn from a suite of hydrodynamical simulations that sample the IGM temperature-density relationship, γ, and temperature at mean density, T {sub 0}, where T(Δ) = T {sub 0}Δ{sup γ} {sup –} {sup 1}. We find that a significant population of partial Lyman-limit systems (LLSs) with a column-density distribution slope of β{sub pLLS} ∼ – 2 are required to explain the data at the low-transmission end of transmission PDF, while uncertainties in the mean Lyα forest transmission affect the high-transmission end. After modeling the LLSs and marginalizing over mean transmission uncertainties, we find that γ = 1.6 best describes the data over our entire redshift range, although constraints on T {sub 0} are affected by systematic uncertainties. Within our model framework, isothermal or inverted temperature-density relationships (γ ≤ 1) are disfavored at a significance of over 4σ, although this could be somewhat weakened by cosmological and astrophysical uncertainties that we did not model.

  12. Mapping the low-surface brightness Universe in the UV band with Lyα emission from IGM filaments

    Science.gov (United States)

    Silva, Marta B.; Kooistra, Robin; Zaroubi, Saleem

    2016-10-01

    A large fraction of the baryonic matter in the Universe is located in filaments in the intergalactic medium (IGM). However, the low surface brightness of these filaments has not yet allowed their direct detection except in very special regions in the circum-galactic medium. Here we simulate the intensity and spatial fluctuations in Lyman alpha (Lyα) emission from filaments in the IGM and discuss the prospects for the next generation of space-based instruments to detect the low-surface brightness Universe at ultraviolet (UV) wavelengths. Starting with a high-resolution N-body simulation, we obtain the dark matter density fluctuations and associate baryons with the dark matter particles assuming that they follow the same spatial distribution. The IGM thermal and ionization state is set by a model of the UV background and by the relevant cooling processes for a hydrogen and helium gas. The Lyα emissivity is then estimated, taking into account recombination and collisional excitation processes. We find that the detection of these filaments through their Lyα emission is well in the reach of the next generation of UV space-based instruments and so it should be achieved in the next decade. The density field is populated with halos and galaxies and their Lyα emission is estimated. Galaxies are treated as foregrounds and so we discuss methods to reduce their contamination from observational maps. Finally, we estimate the UV continuum background as a function of the redshift of the Lyα emission line and discuss how this continuum can affect observations.

  13. HLA-DQBl*0402 alleles polymorphisms detected in Javanese HIV patients with positive anti-Toxoplasma gondii IgM

    Science.gov (United States)

    Sari, Yulia; Haryati, Sri; Prasetyo, Afiono Agung; Hartono, Adnan, Zainal Arifin

    2017-02-01

    The human leukocyte antigen (HLA)-DQB1 gene polymorphisms may associated with the infection risk of Toxoplasma gondii in HIV patients. The HLA-DQB1*0402 in HIV-1-positive patients could be considered risk factors for developing neurological opportunistic infections, mainly Toxoplasma encephalitis. However, the HLA-DQB1*0402 gene polymorphisms status in the Javanese HIV patients is unknown. This study evaluated the prevalence of HLA-DQB*0402 alleles polymorphisms in Javanese HIV patients with positive anti-Toxoplasma gondii IgM status. Since 2009 our research group performing a molecular epidemiology of blood borne viruses in Central Java Indonesia, by collecting the epidemiological and clinical data from the high risk communities. All blood samples were screened for blood borne pathogens by serological and molecular assays including for HIV and Toxoplasma gondii. The genomic DNA was isolated from the whole blood samples. Genetic polymorphisms of HLA-DQB1*0402 alleles were detected with polymerase chain reaction-sequence-specific primers (PCR-SSPs) technique. The genotypes were defined according to generated fragment patterns in the agarose gel electrophoresis analysis of PCR products. All of the samples were tested at least in duplicate. HLA-DQB1*0402 alleles were detected in 20.8% (16/77) patients and not detected in all HIV positive samples with negative anti-Toxoplasma gondii IgM status (n= 200). The HLA-DQB1*0402 alleles polymorphisms were detected in Javanese HIV patients with positive anti-Toxoplasma gondii IgM. The polymorphisms found may have association with the infection risk of Toxoplasma gondii in HIV patients.

  14. Cocoa and cocoa fibre differentially modulate IgA and IgM production at mucosal sites.

    Science.gov (United States)

    Massot-Cladera, Malen; Franch, Àngels; Pérez-Cano, Francisco J; Castell, Margarida

    2016-05-01

    Previous studies have shown that a 10 % cocoa (C10) diet, containing polyphenols and fibre among others, modifies intestinal and systemic Ig production. The present study aimed at evaluating the impact of C10 on IgA and IgM production in the intestinal and extra-intestinal mucosal compartments, establishing the involvement of cocoa fibre (CF) in such effects. Mechanisms by which C10 intake may affect IgA synthesis in the salivary glands were also studied. To this effect, rats were fed either a standard diet, a diet containing C10, CF or inulin. Intestinal (the gut wash (GW), Peyer's patches (PP) and mesenteric lymph nodes (MLN)) and extra-intestinal (salivary glands) mucosal tissues and blood samples were collected for IgA and IgM quantification. The gene expressions of IgA production- and homing-related molecules were studied in the salivary glands. The C10 diet decreased intestinal IgA and IgM production. Although the CF diet decreased the GW IgA concentration, it increased PP, MLN and serum IgA concentrations. Both the C10 and the CF diets produced a down-regulatory effect on IgA secretion in the extra-intestinal tissues. The C10 diet interacted with the mechanisms involved in IgA synthesis, whereas the CF showed particular effects on the homing and transcytosis of IgA across the salivary glands. Overall, CF was able to up-regulate IgA production in the intestinal-inductor compartments, whereas it down-regulated its production at the mucosal-effector ones. Further studies must be directed to ascertain the mechanisms involved in the effect of particular cocoa components on gut-associated lymphoid tissue.

  15. Neutral beam dump with cathodic arc titanium gettering.

    Science.gov (United States)

    Smirnov, A; Krivenko, A S; Murakhtin, S V; Savkin, V Ya; Korepanov, S A; Putvinski, S

    2011-03-01

    An incomplete neutral beam capture can degrade the plasma performance in neutral beam driven plasma machines. The beam dumps mitigating the shine-through beam recycling must entrap and retain large particle loads while maintaining the beam-exposed surfaces clean of the residual impurities. The cathodic arc gettering, which provides high evaporation rate coupled with a fast time response, is a powerful and versatile technique for depositing clean getter films in vacuum. A compact neutral beam dump utilizing the titanium arc gettering was developed for a field-reversed configuration plasma sustained by 1 MW, 20-40 keV neutral hydrogen beams. The titanium evaporator features a new improved design. The beam dump is capable of handling large pulsed gas loads, has a high sorption capacity, and is robust and reliable. With the beam particle flux density of 5 × 10(17) H∕(cm(2) s) sustained for 3-10 ms, the beam recycling coefficient, defined as twice the ratio of the hydrogen molecular flux leaving the beam dump to the incident flux of high-energy neutral atoms, is ∼0.7. The use of the beam dump allows us to significantly reduce the recycling of the shine-through neutral beam as well as to improve the vacuum conditions in the machine.

  16. Neutralizing antibodies against two HIV-1 strains in consecutively collected serum samples: cross neutralization and association to HIV-1 related disease

    DEFF Research Database (Denmark)

    Arendrup, M; Nielsen, C M; Hansen, J E

    1992-01-01

    97 sera collected during a 10-year period from 10 HIV-1 infected individuals were tested for neutralizing capacity against a virus isolate FICPH-22 obtained from a Danish AIDS patient, and the laboratory strain HTLV-IIIB. Three patterns of serum neutralizing activity were demonstrated: (a) patients...... developing high neutralizing activity against both HIV strains; (b) patients developing high neutralizing activity against the Danish virus isolate; and (c) patients developing only low titers of neutralizing antibodies (NA) against both HIV strains. The HTLV-IIIB strain was less sensitive to serum...... neutralization than the FICPH-22 isolate and the appearance of NA against HTLV-IIIB was typically lacking several years behind that against FICPH-22 indicating a broadening of the NA response over time. No difference in clinical outcome was observed comparing patients reaching high titers of NA and patients...

  17. Association of beta2-glycoprotein I IgG and IgM antibodies with thrombosis and thrombocytopenia

    DEFF Research Database (Denmark)

    Voss, Anne-Sofie Boertmann; Jacobsen, Søren; Heegaard, Niels Henrik Helweg

    2001-01-01

    Antiphospholipid antibodies (APA) have been known for decades. Their relation to clinical manifestations, primarily thromboses and thrombocytopenia, was recognised in the 1980s. In this clinical study two cohorts of patients, a population-based (84 patients with systemic lupus erythematosus (SLE......)) and a hospital-based (87 patients with SLE and 53 with other connective tissue diseases) were investigated for APA and associated clinical manifestations. Anticardiolipin antibodies (ACA) of IgG and IgM classes were found in 13 and 38% of the population-based patients and in 29 and 58% of the hospital...

  18. Report of a joint DMRQC/Organon field trial to detect hepatitis A IgM by ELISA.

    Science.gov (United States)

    Supran, E M; Craske, J; Hart, R J; Kurtz, J B; Parry, J V; Skidmore, S J; Gardner, P S

    1983-10-01

    The results of a field trial of a joint DMRQC/Organon ELISA kit for the detection of hepatitis A IgM antibody are reported. The participating laboratories were asked to use the kit to test a panel of 360 specimens consisting of duplicate coded samples of 180 sera. The panel was also tested by MACRIA in the Virus Reference Laboratory, Colindale. The ELISA was shown to be specific and sensitive giving good discrimination between acute and late convalescent hepatitis A sera. It was proposed that the same cut-off control as is used in the RIA (equivalent to 10 RIA units) should be adopted for the ELISA also.

  19. 49例 IgM 沉积儿童原发性肾小球疾病的临床特征及预后%Clinical features and prognosis of 49 cases of childhood primary glomerulopathy with IgM deposition

    Institute of Scientific and Technical Information of China (English)

    潘晓芬; 杨赛; 刘玉玲; 李小琳; 付四毛; 周涛; 雷辛衍; 罗序峰; 林国模; 黄东明

    2016-01-01

    biopsy in pediatric nephrology of Zhongshan Boai Hospital during May 2009 to June 2015, was analyzed.According to whether there was IgM deposition in renal tissue pathology immunofluorescence test , patients were divided into IgM group ( n =49 ) and non-IgM group ( n =34 ) , and their clinical features, pathological characteristics , curative effect and prognosis were analyzed .Results Clinical diagnosis indicated 37 cases of simple hematuria, 30 cases of nephrotic syndrome, 9 cases of acute nephritic syndrome, and 7 cases of proteinuria.In IgM group mesangial proliferative glomerulonephritis was the major lesion and occupied 59.2%(29 cases), which was significantly higher than that (17.6%, 6 cases) in non-IgM group (χ2 =14.200, P0.05).Follow-up for 6 months to 6.5 years revealed that there were 19 cases of remission (38.8%) in IgM group and 22 cases (62.9%) in non-IgM group, respectively, and the difference between two groups was significant (χ2 =5.339,P=0.020).Conclusion The clinical features of primary glomerulopathy with IgM deposition are similar to those without deposition .Mesangial proliferative glomerulonephritis is the majority in renal pathology , and a few cases may occur basement membrane thickening and small artery wall lesions .Treatment responses to steroid is similar .Remission rate of hematuria and proteinuria is low, so a long-term tracking is needed .

  20. Instructed neutralization, spontaneous neutralization and prevented neutralization after an obsession-like thought.

    NARCIS (Netherlands)

    M. van den Hout; M. Kindt; T. Weiland; M. Peters

    2002-01-01

    Building on 2 earlier experiments (S. Rachman et al [1996] and M. A. van den Hout [2001]) the present study investigated the effects of neutralizing the consequences of an obsession-like thought in healthy participants. Just like in the earlier studies, writing out and thinking of such a thought gen

  1. Promotion of classic neutral bile acids synthesis pathway is responsible for cholesterol-lowing effect of Si-miao-yong-an decoction: Application of LC-MS/MS method to determine 6 major bile acids in rat liver and plasma.

    Science.gov (United States)

    Liu, Ziying; Zhang, Yu; Zhang, Ruowen; Gu, Liqiang; Chen, Xiaohui

    2017-02-20

    Si-miao-yong-an decoction (SMYAD), a traditional Chinese medicine formula, significantly reduced plasma TC, LDL-c levels and increased HDL-c level in hyperlipidemia rats. Liver function test and tissue section examination indicated that SMYAD improved liver function and reduced fat accumulation in hyperlipidemia rat liver. A LC-MS/MS method was established and well validated to evaluate major bile acids derived from cholesterol metabolism through the classic neutral pathway and the alternative acidic pathway (cholic acid, chenodeoxycholic acid and their taurine and glycine conjugates) in liver and plasma. Increased total 6 bile acids concentrations in both liver and plasma were observed after oral administration of 12g/kg/d, 24g/kg/d and 36g/kg/d of SMYAD in a dose dependent manner which contributed to eliminate of cholesterol. Cholic acid, taurocholic acid and glycocholic acid act as the main products of bile acid classic neutral synthesis pathway and show sharp increase (p<0.01) after treatment of SMYAD at dosage of 24-36g/kg/d. For liver samples, taurocholic acid level act as the largest growth section, while in plasma samples, cholic acid act as the largest growth section after SMYAD treatment, compared with Model group. By contrast, the main products of alternative acidic pathway (chenodeoxycholic acid and its glycine and taurine conjugates) show no significant increase after treatment of SMYAD. In conclusion, the cholesterol lowing effect of SMYAD may be related with the accelerated transformation of cholesterol into bile acids through the classic neutral pathway.

  2. Serum carbohydrate-binding IgM are present in Vietnamese striped catfish (Pangasianodon hypophthalmus) but not in North African catfish (Clarias gariepinus).

    Science.gov (United States)

    Giang, Duong Thi Huong; Van Driessche, Edilbert; Beeckmans, Sonia

    2012-02-01

    Pangasianodon hypophthalmus serum was fractionated by affinity chromatography on 12 different Sepharose-carbohydrate columns and proteins eluted by the corresponding sugar. Binding to the affinity matrices is dependent on Ca(2+) ions. Upon gel filtration using Superose-12, essentially one fraction was obtained, eluting as a protein with a molecular mass of about 900 kDa. SDS-PAGE in reducing conditions revealed the presence of large (72 kDa) subunits (H-chains) and one up to three small (24, 26 and/or 28-29 kDa) subunits (L-chains). The isolated proteins were shown to be IgM since they bind monoclonal anti-P. hypophthalmus IgM antibodies. Rabbit polyclonal anti-galactose-binding IgM only cross-react with some sugar-binding IgM. The H-chains of the anti-carbohydrate IgM are glycosylated. Circular dichroism studies revealed that the IgMs have an "all-β" type of structure, and that Ca(2+) ions, though essential for carbohydrate-binding activity, are not required for the structural integrity of the molecules. In non-reducing SDS-PAGE, only monomers and halfmers were obtained, showing that there are no disulfide bonds linking the monomers, and that a disulfide bond connecting both H-chains within one monomer is only present in 45% of the molecules. Both the monomers and the halfmers display molecular mass heterogeneity which is indicative for redox forms at the level of the intradomain disulfide bonds. The native carbohydrate-binding IgMs agglutinate erythrocytes from different animals, as well as fish pathogenic bacteria. Similar proteins could not be isolated from another catfish, Clarias gariepinus.

  3. Serum anti-phenolic glycolipid-1 IgA correlates to IgM isotype in leprosy patients: a possible candidate for seroepidemiological surveys?

    Science.gov (United States)

    de Macedo, Alexandre C; Guimarães, Juliana A; Rodrigues, Raphael O; Araújo, Thiago D V; Tavares, Clodis M; Cabral, Paula B; de Moraes-Pinto, Maria Isabel; Nagao-Dias, Aparecida T

    2017-06-08

    The aim of this study was to compare serum anti-phenolic glycolipid-1 IgA, IgG, and IgM levels in leprosy patients and controls. Analysis of anti-PGL-1 IgA, IgG, or IgM in serum samples from multibacillary (MB, n=32) and paucibacillary (PB, n=22) leprosy patients, and in non-endemic controls (n=17), using an indirect enzyme-linked immunosorbent assay. A strong correlation between serum IgM and IgA isotypes was found (r=.745, PIgA and IgM tests. Based on the ROC curves, the cut-off values were selected and the parameters of validation were calculated. Considering the clinical forms altogether, the diagnostic sensitivities were 50.0% for IgA, 22.2% for IgG, and 74.1% for IgM. The positive (VPP) and negative (VPN) predictive values were estimated for each isotype. For IgA, the VPP and VPN were, respectively, 100.0% (87.0%-100.0%; 95% confidence interval) and 38.7% (24.4%-54.5%); for IgG, 100% (87.0%-100.0%) and 28.8% (17.8%-42.1%), respectively; and for IgM, 95.2% (83.8%-99.4%) and 51.7% (32.5%-70.6%), respectively. Despite the limiting factors, anti-PGL1 IgA correlates to IgM levels and it could be considered as a possible laboratorial tool to be also used, for instance, in serological follow-up studies. © 2017 Wiley Periodicals, Inc.

  4. Modulation of natural IgM autoantibodies to oxidative stress-related neo-epitopes on apoptotic cells in newborns of mothers with anti-Ro autoimmunity.

    Science.gov (United States)

    Grönwall, Caroline; Clancy, Robert M; Getu, Lelise; Lloyd, Katy A; Siegel, Don L; Reed, Joanne H; Buyon, Jill P; Silverman, Gregg J

    2016-09-01

    At birth, the human immune system already contains substantial levels of polymeric IgM, that include autoantibodies to neo-epitopes on apoptotic cells (ACs) that are proposed to play homeostatic and anti-inflammatory roles. Yet the biologic origins and developmental regulation of these naturally arising antibodies remain poorly understood. Herein, we report that levels of IgM-antibodies to malondialdehyde (MDA) protein adducts, a common type of in vivo generated oxidative stress-related neoepitope, directly correlate with the relative binding of neonatal-IgM to ACs. Levels of IgM to phosphorylcholine (PC), a natural antibody prevalent in adults, were relatively scant in cord blood, while there was significantly greater relative representation of IgM anti-MDA antibodies in newborns compared to adults. To investigate the potential interrelationships between neonatal IgM with pathogenic IgG-autoantibodies, we studied 103 newborns born to autoimmune mothers with IgG anti-Ro (i.e., 70 with neonatal lupus and 33 without neonatal lupus). In these subjects the mean levels of IgM anti-Ro60 were significantly higher than in the newborns from non-autoimmune mothers. In contrast, levels of IgM anti-MDA in IgG anti-Ro exposed neonates were significantly lower than in neonates from non-autoimmune mothers. The presence or absence of neonatal lupus did not appear to influence the total levels of IgM in the anti-Ro exposed newborns. Taken together, our studies provide evidence that the immune development of the natural IgM-repertoire may be affected, and become imprinted by, the transfer of maternal IgG into the fetus.

  5. Broadly Neutralizing Activity of Zika Virus-Immune Sera Identifies a Single Viral Serotype

    Directory of Open Access Journals (Sweden)

    Kimberly A. Dowd

    2016-08-01

    Full Text Available Recent epidemics of Zika virus (ZIKV have been associated with congenital malformation during pregnancy and Guillain-Barré syndrome. There are two ZIKV lineages (African and Asian that share >95% amino acid identity. Little is known regarding the ability of neutralizing antibodies elicited against one lineage to protect against the other. We investigated the breadth of the neutralizing antibody response following ZIKV infection by measuring the sensitivity of six ZIKV strains to neutralization by ZIKV-confirmed convalescent human serum or plasma samples. Contemporary Asian and early African ZIKV strains were similarly sensitive to neutralization regardless of the cellular source of virus. Furthermore, mouse immune serum generated after infection with African or Asian ZIKV strains was capable of neutralizing homologous and heterologous ZIKV strains equivalently. Because our study only defines a single ZIKV serotype, vaccine candidates eliciting robust neutralizing antibody responses should inhibit infection of both ZIKV lineages, including strains circulating in the Americas.

  6. Experimental evidence for direct in situ binding of IgM and IgT to early trophonts of Ichthyophthirius multifiliis (Fouquet) in the gills of rainbow trout, Oncorhynchus mykiss (Walbaum)

    DEFF Research Database (Denmark)

    Jørgensen, Louise von Gersdorff; Heinecke, Rasmus Demuth; Skjødt, Karsten

    2011-01-01

    Freshwater fish are able to mount a protective immune response against the parasite Ichthyophthirius multifiliis (Ich) following a non-lethal exposure. Factors involved in immunity comprise cellular and humoral factors, but antibodies have been suggested to play a prominent role in protection....... However, host antibodies have not yet been demonstrated to bind to the parasite in situ. By the use of immunohistochemical techniques, this study demonstrated that IgT and IgM bind to surface structures, including cilia, on the early feeding stage of the parasite in the gills of immune rainbow trout......, Oncorhynchus mykiss, shortly (2 h) after invasion. No binding of IgT and no or only a weak binding of IgM was observed on the parasites in the gills of similarly exposed but naïve rainbow trout. This study indicates that antibodies play an important part in the protection of immune fish against Ich although...

  7. Rocket Experiment For Neutral Upwelling

    Science.gov (United States)

    Kenward, D. R.; Lessard, M.

    2015-12-01

    Observations from the CHAMP satellite from 2004 show relatively small scale heating in the thermosphere. Several different mechanisms have been proposed to explain this phenomenon. The RENU 2 rocket mission includes a suite of 14 instruments which will acquire data to help understand processes involved in neutral upwelling in the cusp. Neutral, ion, and electron measurements will be made to provide an assessment of the upwelling process. SUPERDarn measurements of large- scale Joule heating in the cusp during overflight will also be acquired. Small-scale data which could possibly be associated with Alfvén waves, will be acquired using onboard electric field measurements. In-situ measurement of precipitating electrons and all other measurements will be used in thermodynamic and electrodynamic models for comparison to the observed upwelling.

  8. Optical Neutrality: Invisibility without Cloaking

    CERN Document Server

    Hodges, Reed; Durach, Maxim

    2016-01-01

    We show that it is possible to design an invisible wavelength-sized metal-dielectric metamaterial object without evoking cloaking. Our approach is an extension of the neutral inclusion concept by Zhou and Hu [Phys.Rev.E 74, 026607 (2006)] to Mie scatterers. We demonstrate that an increase of metal fraction in the metamaterial leads to a transition from dielectric-like to metal-like scattering, which proceeds through invisibility or optical neutrality of the scatterer. Formally this is due to cancellation of multiple scattering orders, similarly to plasmonic cloaking introduced by Alu and Engheta [Phys.Rev.E 72, 016623 (2005)], but without introduction of the separation of the scatterer into cloak and hidden regions.

  9. Neutral Hydrogen in Galaxy Groups

    CERN Document Server

    McKay, N P F; Brough, S; Forbes, D A; Barnes, D G

    2002-01-01

    We present preliminary results from a study of the neutral hydrogen (HI) properties of an X-ray selected sample of nearby loose galaxy groups. This forms part of a multi-wavelength investigation (X-ray, optical and radio) of the formation and evolution of galaxies within a group environment. Some initial findings of an ATNF Parkes Multibeam wide-area neutral hydrogen imaging survey of 17 nearby galaxy groups include two new, potentially isolated clouds of HI in the NGC 1052 and NGC 5044 groups and significant amounts of HI within the group virial radii of groups NGC 3557 and IC 1459 - two groups with complex X-ray structures that suggest they may still be in the act of virialisation. Here we present ATCA high-resolution synthesis-imaging follow-up observations of the distribution and kinematics of HI in these four groups.

  10. Neutrality and the social contract

    Directory of Open Access Journals (Sweden)

    Ian J. Carroll

    2009-06-01

    Full Text Available Given the fact of moral disagreement, theories of state neutrality which rely on moral premises will have limited application, in that they will fail to motivate anyone who rejects the moral premises on which they are based. By contrast, contractarian theories can be consistent with moral scepticism, and can therefore avoid this limitation. In this paper, I construct a contractarian model which I claim is sceptically consistent and includes a principle of state neutrality as a necessary condition. The principle of neutrality which I derive incorporates two conceptions of neutrality (consequential neutrality and justificatory neutrality which have usually been thought of as distinct and incompatible. I argue that contractarianism gives us a unified account of these conceptions. Ultimately, the conclusion that neutrality can be derived without violating the constraint established by moral scepticism turns out to rely on an assumption of equal precontractual bargaining power. I do not attempt to defend this assumption here. If the assumption cannot be defended in a sceptically consistent fashion, then the argument for neutrality given here is claimed to be morally minimal, rather than fully consistent with moral scepticism. L’existence d’un désaccord sur les questions morales fait en sorte que les constructions théoriques de la neutralité de l’État se fondant sur des prémisses morales ne peuvent avoir qu’une application limitée, car elles échouent à motiver quiconque rejette ces prémisses fondatrices. Par opposition, les théories contractualistes peuvent s’accommoder d’un scepticisme moral et peuvent donc éviter cette limitation. Cet article développe un modèle contractualiste compatible avec le scepticisme et qui inclut comme condition nécessaire la neutralité de l’État. Le principe de neutralité que je dérive à partir de ce modèle incorpore deux conceptions de la neutralité, soit la neutralité des cons

  11. Optimization of Neutral Atom Imagers

    Science.gov (United States)

    Shappirio, M.; Coplan, M.; Balsamo, E.; Chornay, D.; Collier, M.; Hughes, P.; Keller, J.; Ogilvie, K.; Williams, E.

    2008-01-01

    The interactions between plasma structures and neutral atom populations in interplanetary space can be effectively studied with energetic neutral atom imagers. For neutral atoms with energies less than 1 keV, the most efficient detection method that preserves direction and energy information is conversion to negative ions on surfaces. We have examined a variety of surface materials and conversion geometries in order to identify the factors that determine conversion efficiency. For chemically and physically stable surfaces smoothness is of primary importance while properties such as work function have no obvious correlation to conversion efficiency. For the noble metals, tungsten, silicon, and graphite with comparable smoothness, conversion efficiency varies by a factor of two to three. We have also examined the way in which surface conversion efficiency varies with the angle of incidence of the neutral atom and have found that the highest efficiencies are obtained at angles of incidence greater then 80deg. The conversion efficiency of silicon, tungsten and graphite were examined most closely and the energy dependent variation of conversion efficiency measured over a range of incident angles. We have also developed methods for micromachining silicon in order to reduce the volume to surface area over that of a single flat surface and have been able to reduce volume to surface area ratios by up to a factor of 60. With smooth micro-machined surfaces of the optimum geometry, conversion efficiencies can be increased by an order of magnitude over instruments like LENA on the IMAGE spacecraft without increase the instruments mass or volume.

  12. Optimization of Neutral Atom Imagers

    Science.gov (United States)

    Shappirio, M.; Coplan, M.; Balsamo, E.; Chornay, D.; Collier, M.; Hughes, P.; Keller, J.; Ogilvie, K.; Williams, E.

    2008-01-01

    The interactions between plasma structures and neutral atom populations in interplanetary space can be effectively studied with energetic neutral atom imagers. For neutral atoms with energies less than 1 keV, the most efficient detection method that preserves direction and energy information is conversion to negative ions on surfaces. We have examined a variety of surface materials and conversion geometries in order to identify the factors that determine conversion efficiency. For chemically and physically stable surfaces smoothness is of primary importance while properties such as work function have no obvious correlation to conversion efficiency. For the noble metals, tungsten, silicon, and graphite with comparable smoothness, conversion efficiency varies by a factor of two to three. We have also examined the way in which surface conversion efficiency varies with the angle of incidence of the neutral atom and have found that the highest efficiencies are obtained at angles of incidence greater then 80deg. The conversion efficiency of silicon, tungsten and graphite were examined most closely and the energy dependent variation of conversion efficiency measured over a range of incident angles. We have also developed methods for micromachining silicon in order to reduce the volume to surface area over that of a single flat surface and have been able to reduce volume to surface area ratios by up to a factor of 60. With smooth micro-machined surfaces of the optimum geometry, conversion efficiencies can be increased by an order of magnitude over instruments like LENA on the IMAGE spacecraft without increase the instruments mass or volume.

  13. Neutral Naturalness with Bifundamental Gluinos

    CERN Document Server

    Gherghetta, Tony; Thomas, Zachary

    2016-01-01

    We study constraints on one-loop neutral naturalness at the LHC by considering gluon partners which are required to ameliorate the tuning in the Higgs mass-squared arising at two loops. This is done with a simple orbifold model of folded supersymmetry which not only contains color-neutral stops but also bifundamental gluinos that are charged under the Standard Model color group $SU(3)_C$ and a separate $SU(3)_C'$ group. The bifundamental gluinos reduce the Higgs mass tuning at two loops and maintain naturalness provided the gluinos are lighter than approximately 1.9 TeV for a 5 TeV cutoff scale. Limits from the LHC already forbid bifundamental gluinos below 1.4 TeV, and other non-colored states such as electroweakinos, $Z'$ bosons and dark sector bound states may be probed at future colliders. The search for bifundamental gluinos therefore provides a direct probe of one-loop neutral naturalness that can be fully explored at the LHC.

  14. Neutral naturalness with bifundamental gluinos

    Science.gov (United States)

    Gherghetta, Tony; Nguyen, Minh; Thomas, Zachary

    2016-12-01

    We study constraints on one-loop neutral naturalness at the LHC by considering gluon partners which are required to ameliorate the tuning in the Higgs mass-squared arising at two loops. This is done with a simple orbifold model of folded supersymmetry which not only contains color-neutral stops but also bifundamental gluinos that are charged under the Standard Model color group S U (3 )C and a separate S U (3 )C' group. The bifundamental gluinos reduce the Higgs mass tuning at two loops and maintain naturalness provided the gluinos are lighter than approximately 1.9 TeV for a 5 TeV cutoff scale. Limits from the LHC already forbid bifundamental gluinos below 1.4 TeV, and other noncolored states such as electroweakinos, Z' bosons and dark sector bound states may be probed at future colliders. The search for bifundamental gluinos therefore provides a direct probe of one-loop neutral naturalness that can be fully explored at the LHC.

  15. The Affective Consequences of Cognitive Inhibition: Devaluation or Neutralization?

    Science.gov (United States)

    Frischen, Alexandra; Ferrey, Anne E.; Burt, Dustin H. R.; Pistchik, Meghan; Fenske, Mark J.

    2012-01-01

    Affective evaluations of previously ignored visual stimuli are more negative than those of novel items or prior targets of attention or response. This has been taken as evidence that inhibition has negative affective consequences. But inhibition could act instead to attenuate or "neutralize" preexisting affective salience, predicting opposite…

  16. Development and evaluation of a Sarcocystis neurona-specific IgM capture enzyme-linked immunosorbent assay.

    Science.gov (United States)

    Murphy, J E; Marsh, A E; Reed, S M; Meadows, C; Bolten, K; Saville, W J A

    2006-01-01

    Equine protozoal myeloencephalitis (EPM) is a serious neurologic disease of horses caused primarily by the protozoal parasite Sarcocystis neurona. Currently available antemortem diagnostic testing has low specificity. The hypothesis of this study was that serum and cerebrospinal fluid (CSF) of horses experimentally challenged with S neurona would have an increased S neurona-specific IgM (Sn-IgM) concentration after infection, as determined by an IgM capture enzyme linked immunoassay (ELISA). The ELISA was based on the S neurona low molecular weight protein SNUCD-1 antigen and the monoclonal antibody 2G5 labeled with horseradish peroxidase. The test was evaluated using serum and CSF from 12 horses experimentally infected with 1.5 million S neurona sporocysts and 16 horses experimentally infected with varying doses (100 to 100,000) of S neurona sporocysts, for which results of histopathologic examination of the central nervous system were available. For horses challenged with 1.5 million sporocysts, there was a significant increase in serum Sn-IgM concentrations compared with values before infection at weeks 2-6 after inoculation (P neurona, there were significant increases in serum Sn-IgM concentration at various points in time after inoculation, depending on the challenge dose (P < .01). In addition, there was a significant increase between the CSF Sn-IgM concentrations before and after inoculation (P < .0001). These results support further evaluation of the assay as a diagnostic test during the acute phase of EPM.

  17. Probing the IGM/Galaxy Connection IV: The LCO/WFCCD Galaxy Survey of 20 Fields Surrounding UV Bright Quasars

    CERN Document Server

    Prochaska, J Xavier; Chen, H -W; Cooksey, K L; Mulchaey, J S

    2011-01-01

    We publish the survey for galaxies in 20 fields containing ultraviolet bright quasars (with z_em 0.1 to 0.5) that can be used to study the association between galaxies and absorption systems from the low-z intergalactic medium (IGM). The survey is magnitude limited (R~19.5 mag) and highly complete out to 10' from the quasar in each field. It was designed to detect dwarf galaxies (L ~ 0.1 L*) at an impact parameter rho 1Mpc (z=0.1) from a quasar. The complete sample (all 20 fields) includes R-band photometry for 84718 sources and confirmed redshifts for 2800 sources. This includes 1198 galaxies with 0.005 < z < (z_em - 0.01) at a median redshift of 0.18, which may associated with IGM absorption lines. All of the imaging was acquired with cameras on the Swope 40" telescope and the spectra were obtained via slitmask observations using the WFCCD spectrograph on the Dupont 100" telescope at Las Campanas Observatory (LCO). This paper describes the data reduction, imaging analysis, photometry, and spectral ana...

  18. Measuring alignments between galaxies and the cosmic web at $z \\sim 2-3$ using IGM tomography

    CERN Document Server

    Krolewski, Alex; Lukic, Zarija; White, Martin

    2016-01-01

    Many galaxy formation models predict alignments between galaxy spin and the cosmic web (i.e. the directions of filaments and sheets), leading to intrinsic alignment between galaxies that creates a systematic error in weak lensing measurements. These effects are often predicted to be stronger at high-redshifts ($z\\gtrsim1$) that are inaccessible to massive galaxy surveys on foreseeable instrumentation, but IGM tomography of the Ly$\\alpha$ forest from closely-spaced quasars and galaxies is starting to measure the $z\\sim2-3$ cosmic web with the requisite fidelity. Using mock surveys from hydrodynamical simulations, we examine the utility of this technique, in conjunction with coeval galaxy samples, to measure alignment between galaxies and the cosmic web at $z\\sim2.5$. We show that IGM tomography surveys with $\\lesssim5$ $h^{-1}$ Mpc sightline spacing can accurately recover the eigenvectors of the tidal tensor, which we use to define the directions of the cosmic web. For galaxy spins and shapes, we use a model p...

  19. Interleukin 6 dependence of spontaneous in vitro differentiation of B cells from patients with IgM gammapathy

    Energy Technology Data Exchange (ETDEWEB)

    Levy, Y.; Fermand, J.P.; Schmitt, C.; Seligmann, M.; Brouet, J.C. (Institut National de la Sante et de la Recherche Medicale, Paris (France)); Navarro, S.; Vainchenker, W. (Institut National de la Sante et de la Recherche Medicale, Cretail (France))

    1990-05-01

    Blood B cells from eight patients with clonal lymphoid disorders characterized by monoclonal IgM secretion (four with malignant plasmacytic proliferation typical of Waldenstroem macroglobulinemia and four without overt lymphoid neoplasia) were found to spontaneously differentiate in vitro into plasma cells. In all instances, monoclonal plasma cells were generated from extensively purified B cells or T-cell-depleted peripheral blood mononuclear cells after a 7-day culture period, with a corresponding high rate of IgM secretion into the culture medium. This differentiation occurred in the absence of any cell proliferation process as measured by ({sup 3}H)thymidine uptake at day 2 or 4. Normal B cells did not differentiate under the same experimental conditions. Detection of interleukin 6 (IL-6) bioactivity in all patients' B-cell culture supernatants as well as of IL-6 mRNA in freshly prepared, uncultured B cells in the two cases studied by in situ hybridization suggested that IL-6 secretion by B cells may play a role in this process. Moreover, in the four patients without overt lymphoid proliferation, B-cell differentiation was significantly inhibited in the presence of anti-IL-6 antibodies. In contrast, anti-IL-6 antibodies did not preclude the differentiation into plasma cells of B cells from the four patients with bona fide Waldenstroem macroglobulinemia. These results suggest a two-step pathogenesis for such human lymphoplasmacytic clonal proliferations, the initial stage being characterized by an IL-6-dependent autocrine differentiation pathway.

  20. Correlation of Chlamydia and Chlamydophila spp. IgG and IgM antibodies by microimmunofluorescence with antigen detection methods.

    Science.gov (United States)

    She, Rosemary C; Welch, Ryan; Wilson, Andrew R; Davis, David; Litwin, Christine M

    2011-01-01

    Correlation of serologic titers for Chlamydia trachomatis with other tests has been based on direct fluorescence antibody (DFA) testing and culture, but not on nucleic acid-based tests that are used for screening. We retrospectively reviewed the specificity of antibodies against C. trachomatis, Chlamydia psittaci, and Chlamydophila pneumoniae by microimmunofluorescence (MIF) when compared with DFA, culture, nucleic acid probe, and transcription-mediated amplification. Over a 6-year period, 226 cases had both MIF and one of these other methods performed for comparison. Agreement between C. trachomatis antigen or nucleic acid detection and MIF results was 87% (197/226). C. trachomatis serology had a negative predictive value of 98%, and 10.6% of cases were positive by serology and negative by antigen testing. Of the 13 patients who had a positive C. trachomatis antigen or nucleic acid test result, 9 had IgG and/or IgM titers highest against C. trachomatis, 3 had IgG titers highest against C. pneumoniae, and 1 had undetectable titers for the three chlamydial species. Twenty-five patients had positive IgG and/or IgM titers to C. trachomatis but negative antigen test results. Serologic testing can increase the sensitivity of detecting C. trachomatis infections.

  1. On geometric factors for neutral particle analyzers.

    Science.gov (United States)

    Stagner, L; Heidbrink, W W

    2014-11-01

    Neutral particle analyzers (NPA) detect neutralized energetic particles that escape from plasmas. Geometric factors relate the counting rate of the detectors to the intensity of the particle source. Accurate geometric factors enable quick simulation of geometric effects without the need to resort to slower Monte Carlo methods. Previously derived expressions [G. R. Thomas and D. M. Willis, "Analytical derivation of the geometric factor of a particle detector having circular or rectangular geometry," J. Phys. E: Sci. Instrum. 5(3), 260 (1972); J. D. Sullivan, "Geometric factor and directional response of single and multi-element particle telescopes," Nucl. Instrum. Methods 95(1), 5-11 (1971)] for the geometric factor implicitly assume that the particle source is very far away from the detector (far-field); this excludes applications close to the detector (near-field). The far-field assumption does not hold in most fusion applications of NPA detectors. We derive, from probability theory, a generalized framework for deriving geometric factors that are valid for both near and far-field applications as well as for non-isotropic sources and nonlinear particle trajectories.

  2. Types and Degrees of Vowel Neutrality

    National Research Council Canada - National Science Library

    Rebrus, Péter; Törkenczy, Miklós

    2016-01-01

    This paper argues that neutrality in a harmony system is a gradient property since it is due to a vowel's participation in different patterns that are considered to be indicators of neutral behaviour in harmony...

  3. Validation of IgG, IgM multiplex plasmonic gold platform in French clinical cohorts for the serodiagnosis and follow-up of Toxoplasma gondii infection.

    Science.gov (United States)

    Pomares, Christelle; Zhang, Bo; Arulkumar, Shylaja; Gonfrier, Geraldine; Marty, Pierre; Zhao, Su; Cheng, Steven; Tang, Meijie; Dai, Hongjie; Montoya, Jose G

    2017-03-01

    We report the use of the multiplexed T. gondii IgG, IgM test on plasmonic gold (pGOLD) platform in the setting of T. gondii infection by analyzing 244 sera from Nice, France (seroconversion, chronically infected, non-infected and newborns serum samples). Results were compared with commercial tests for the detection of IgG and IgM and their overall clinical final interpretation of a complete serological profile. The IgG and IgM test results on the platform were in agreement in, respectively, 95% and 93% with the commercial kits. When comparing with the overall clinical interpretation of the serological profile, the agreement reached 99.5% and 97.7% for IgG and IgM, respectively. This innovative pGOLD platform allows detection of both IgG and IgM simultaneously with only ~1 microliter of serum. The multiplexed IgG/IgM test on pGOLD platform is a strong candidate for its use in the massive screening programs for toxoplasmosis during pregnancy.

  4. Diagnostic accuracy of an IgM enzyme-linked immunosorbent assay and comparison with 2 polymerase chain reactions for early diagnosis of human leptospirosis.

    Science.gov (United States)

    Vanasco, N B; Jacob, P; Landolt, N; Chiani, Y; Schmeling, M F; Cudos, C; Tarabla, H; Lottersberger, J

    2016-04-01

    Enzyme-linked immunosorbent assay (ELISA) tests and polymerase chain reaction (PCR) may play a key role for early detection and treatment of human leptospirosis in developing countries. The aims of this study were to develop and validate an IgM ELISA under field conditions and to compare the diagnostic accuracy among IgG, IgM ELISAs, conventional PCR (cPCR), and real-time PCR (rtPCR) for early detection of human leptospirosis. Overall accuracy of IgM ELISA was sensitivity of 87.9%, specificity of 97.0%, and area under the curve of 0.940. When the 4 methods were compared, IgM ELISA showed the greatest diagnostic accuracy (J=0.6) followed by rtPCR (J=0.4), cPCR (J=0.2) and IgG ELISA (J=0.1). Our results support the use of IgM ELISA and rtPCR for early diagnosis of the disease. Moreover, due to their high specificity, they could be also useful to replace or supplement microscopic agglutination test as a confirmatory test, allowing more confirmations.

  5. Evaluación de pruebas de elisa e inmunofluorescencia indirecta para la detección de anticuerpos IgM contra rickettsiosis

    Directory of Open Access Journals (Sweden)

    Elizabeth Anaya

    2008-07-01

    Full Text Available Se evaluó dos pruebas modificadas de ELISA e inmunofluorescencia indirecta (IFI para la detección de IgM basadas en el lisado total de Rickettsia akari para el diagnóstico de Rickettsiosis. Se usaron 55 sueros negativos, 100 sueros positivos confirmados por IFI IgG Total y 15 sueros con diagnóstico confirmado para otras enfermedades bacterianas procedentes de la seroteca del Instituto Nacional de Salud. La prueba de ELISA IgM tuvo una sensibilidad de 78,0%, especificidad de 80,0%, valor predictivo positivo de 87,6% y el valor predictivo negativo de 66,7%, con una reacción cruzada con otras etiologías bacterianas de 20% (3/15. La prueba de IFI IgM tuvo una sensibilidad de 82,0%, especificidad de 91,7%, valor predictivo positivo de 94,3% y valor predictivo negativo de 75,3%, con una reacción cruzada de 13% (2/15. El método ELISA IgM no es una prueba útil, a diferencia de la prueba IFI IgM que podría ser aplicada en el diagnóstico de Rickettsiosis para estudios epidemiológicos y de vigilancia en el Perú.

  6. Reactivity in the Venereal Diseases Research Laboratory test and the Mercia IgM enzyme immunoassay after treatment of early syphilis.

    Science.gov (United States)

    McMillan, A; Young, H

    2008-10-01

    The aim of the study was to compare reactivity in the Mercia immunoglobulin M enzyme immunoassay (IgM EIA) and the Venereal Disease Research Laboratory (VDRL) after treatment of 229 previously untreated patients with early syphilis. At three months, the VDRL and the IgM EIA were negative in 41 (38%) and 71 (62%) cases, respectively; a four-fold or greater decrease in VDRL titre occurred in 106 (99%). At six months, the VDRL and the IgM EIA were negative in 45 (48%) and 69 (71%) patients, respectively; a four-fold or greater decrease in VDRL titre occurred in 88 (95%) and an eight-fold or greater decrease in 80 (86%). At 12 months, the VDRL and the IgM EIA were negative in 35 (70%) and 55 (92%) patients, respectively; a four-fold or greater decrease in VDRL titre occurred in 49 (98%) and an eight-fold or greater decrease in 47 (94%). The Mercia IgM EIA is as sensitive as the VDRL in monitoring treatment of primary syphilis but not as sensitive as the finding of a four-fold or eight-fold decrease in VDRL titre in patients treated for secondary or early latent infection.

  7. Plasma/Neutral-Beam Etching Apparatus

    Science.gov (United States)

    Langer, William; Cohen, Samuel; Cuthbertson, John; Manos, Dennis; Motley, Robert

    1989-01-01

    Energies of neutral particles controllable. Apparatus developed to produce intense beams of reactant atoms for simulating low-Earth-orbit oxygen erosion, for studying beam-gas collisions, and for etching semiconductor substrates. Neutral beam formed by neutralization and reflection of accelerated plasma on metal plate. Plasma ejected from coaxial plasma gun toward neutralizing plate, where turned into beam of atoms or molecules and aimed at substrate to be etched.

  8. Plasma/Neutral-Beam Etching Apparatus

    Science.gov (United States)

    Langer, William; Cohen, Samuel; Cuthbertson, John; Manos, Dennis; Motley, Robert

    1989-01-01

    Energies of neutral particles controllable. Apparatus developed to produce intense beams of reactant atoms for simulating low-Earth-orbit oxygen erosion, for studying beam-gas collisions, and for etching semiconductor substrates. Neutral beam formed by neutralization and reflection of accelerated plasma on metal plate. Plasma ejected from coaxial plasma gun toward neutralizing plate, where turned into beam of atoms or molecules and aimed at substrate to be etched.

  9. CD4 T-Cell-Independent Antibody Response Reduces Enterovirus 71 Lethality in Mice by Decreasing Tissue Viral Loads

    Directory of Open Access Journals (Sweden)

    Li-Chiu Wang

    2012-01-01

    Full Text Available Enterovirus 71 (EV71 has induced fatal encephalitis in hundreds of thousands of infants and young children in the Asia-Pacific region since the past decade. Lymphocyte and antibody responses have been suspected to aggravate EV71-induced neurological symptoms, so anti-inflammatory agents have been used to treat patients with neurological symptoms. In the present study, we found that mice deficient in CD4+ T cells were resistant to EV71 infection as wild-type mice, whereas mice deficient in B cells were highly susceptible to viral infection. Compensation of CD4 T-cell function by other immune cells was not likely, because wild-type mice depleted of CD4+ T cells were also resistant to viral infection. Infected CD4 T-cell-deficient mice produced virus-specific neutralizing antibodies, IgM and IgG. Moreover, adoptive transfer of the virus-specific antibody produced by infected CD4 T-cell-deficient mice protected B-cell-deficient mice from infection by reducing tissue viral loads. Collectively, our results show that the CD4 T-cell-independent antibody response promotes the survival of EV71-infected mice and suggest great potential for the use of vaccines and neutralizing antibodies to reduce fatal symptoms in patients.

  10. Electroweak Chiral Lagrangian for Neutral Higgs Boson

    Institute of Scientific and Technical Information of China (English)

    WANG Shun-Zhi; WANG Qing

    2008-01-01

    A neutral Higgs boson is added into the traditional electroweak chiral Lagrangian by writing down all possible high dimension operators. The matter part of the Lagrangian is investigated in detail. We find that if Higgs field dependence of Yukawa couplings can be factorized out, there will be no flavour changing neutral couplings; neutral Higgs can induce coupling between light and heavy neutrinos.

  11. The comparison between the humoral response and the neutralizing capacity of sheep serum inoculated with natural venom and Co{sup 60} irradiated venom from Crotalus durissus terrificus (Laurenti, 1768)

    Energy Technology Data Exchange (ETDEWEB)

    Netto, D.P. [Universidade Estadual de Londrina, PR (Brazil). Centro de Ciencias Agrarias. Dept. de Medicina Veterinaria Preventiva]. E-mail: mnetto@uel.br

    2000-07-01

    Crotalus durissus terrificus venom was irradiated with Co{sup 60} to investigate the effects of antigen-irradiation on antivenom production in sheep. Twelve sheep were divided in two groups of 6. One group received irradiated, while the other received natural venom. Three doses of antigen were given at monthly intervals. The toxic activity of the venom was assessed by LD{sub 50} in mice. Weekly blood samples were obtained to evaluate anti-crotalic serum titers by indirect ELISA, neutralization capacity, and serum potency. A complete blood count, plasma protein and fibrinogen concentration, and serum albumin and globulin were also determined. At end of the experiment, the animals were challenged with ovine LD{sub 50}, without clinical abnormalities. (author)

  12. Neutralization of HIV-1: a paradox of humoral proportions.

    Science.gov (United States)

    Nara, P L; Garrity, R R; Goudsmit, J

    1991-07-01

    . Thus a relatively restricted clonal-dominance of the neutralization response results. The V3 domain, apparently in concert with the rest of the molecule, provides an epitope that can tolerate and utilize its conformational flexibility to allow immune escape while maintaining its functional role in infectivity. Sixteen other putative epitopes have been described as being involved in the induction of neutralizing Ig. Currently the biologically functional role of neutralizing Ig to these other epitopes are complicated by a prior lack of knowledge and appreciation of the in vitro variables affecting their measurements.(ABSTRACT TRUNCATED AT 400 WORDS)

  13. [IgM, IgG and IgG subclass antibodies to herpes simplex virus in persons of different ages].

    Science.gov (United States)

    Zazimko, L A; Kuzenkova, A V; Ivanova, I A; Bashukova, S S; Rybakov, V P; Klimovich, V B; Shitikova, G S

    2000-01-01

    IgM, IgG antibodies to herpes simplex virus and their subclases were investigated in 565 subjects of different age tested at virological laboratories of St. Petersburg in 1996-1997. The majority of these subjects had a history of herpes infection and 21.5% had IgM antibodies to herpes simplex virus (HSV), marker of acute herpetic infection. Besides IgM, IgG1 antibodies can be referred to early antibodies appearing during the acute stage of herpetic infection. The predominant subclass was HSV IgG3 antibodies. As for IgG4, they were completely absent in infants aged under 1 year, were detected in 6.2% children aged under 14 years, and were present in 12.2-12.5% adults.

  14. Effect of Hormone Replacement Therapy on Serum Complement (C3,C4) and Immunoglobulin (IgG, IgM) Levels in Post-menopausal Women

    Institute of Scientific and Technical Information of China (English)

    Yi LIU; Liqun LV

    2008-01-01

    Serum C3, C4, IgG and IgM levels were evaluated in healthy post-menopausal women receiving short-term hormone replacement therapy (HRT) regimens and in untreated women. Serum C3, C4, IgM and IgG levels were assessed in 54 women receiving HRT therapy (CEE 0.625 mg+MPA 2.5 mg/day), and in 54 control women not receiving HRT. The results showed that the mean serum C3 and C4 levels were significantly higher in women receiving HRT than those untreated women (P<0.01). There was significant difference in lgG and IgM levels between two groups. It was con-cluded that HRT might be involved in the development of cardiovascular diseases through inflamma- tory mechanisms, as suggested by increased serum levels of C3 and C4.

  15. ELISA detection of IgM antibodies against phenolic glycolipid-I in the management of leprosy: a comparison between laboratories.

    Science.gov (United States)

    Meeker, H C; Levis, W R; Sersen, E; Schuller-Levis, G; Brennan, P J; Buchanan, T M

    1986-12-01

    IgM antibodies to the phenolic glycolipid-I (PGL-I) antigen of Mycobacterium leprae were detected by different ELISA techniques in three laboratories (in New York, Colorado, Seattle, U.S.A.). The agreement on seropositivity and overall correlation between techniques was excellent. A positive linear correlation between the bacterial index (BI) and anti-PGL-I IgM, previously reported by the New York laboratory, was detected by all techniques. The role of erythema nodosum leprosum in decreasing the relationship of BI versus anti-PGL-I IgM was seen by the New York laboratory with sera diluted 1:20 and ABTS substrate solution and by the Colorado laboratory but not by New York with sera at 1:300 and OPD substrate or by the Seattle laboratory.

  16. Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection.

    Directory of Open Access Journals (Sweden)

    Rami Sommerstein

    2015-11-01

    Full Text Available Arenaviruses such as Lassa virus (LASV can cause severe hemorrhagic fever in humans. As a major impediment to vaccine development, delayed and weak neutralizing antibody (nAb responses represent a unifying characteristic of both natural infection and all vaccine candidates tested to date. To investigate the mechanisms underlying arenavirus nAb evasion we engineered several arenavirus envelope-chimeric viruses and glycan-deficient variants thereof. We performed neutralization tests with sera from experimentally infected mice and from LASV-convalescent human patients. NAb response kinetics in mice correlated inversely with the N-linked glycan density in the arenavirus envelope protein's globular head. Additionally and most intriguingly, infection with fully glycosylated viruses elicited antibodies, which neutralized predominantly their glycan-deficient variants, both in mice and humans. Binding studies with monoclonal antibodies indicated that envelope glycans reduced nAb on-rate, occupancy and thereby counteracted virus neutralization. In infected mice, the envelope glycan shield promoted protracted viral infection by preventing its timely elimination by the ensuing antibody response. Thus, arenavirus envelope glycosylation impairs the protective efficacy rather than the induction of nAbs, and thereby prevents efficient antibody-mediated virus control. This immune evasion mechanism imposes limitations on antibody-based vaccination and convalescent serum therapy.

  17. Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection.

    Science.gov (United States)

    Sommerstein, Rami; Flatz, Lukas; Remy, Melissa M; Malinge, Pauline; Magistrelli, Giovanni; Fischer, Nicolas; Sahin, Mehmet; Bergthaler, Andreas; Igonet, Sebastien; Ter Meulen, Jan; Rigo, Dorothée; Meda, Paolo; Rabah, Nadia; Coutard, Bruno; Bowden, Thomas A; Lambert, Paul-Henri; Siegrist, Claire-Anne; Pinschewer, Daniel D

    2015-11-01

    Arenaviruses such as Lassa virus (LASV) can cause severe hemorrhagic fever in humans. As a major impediment to vaccine development, delayed and weak neutralizing antibody (nAb) responses represent a unifying characteristic of both natural infection and all vaccine candidates tested to date. To investigate the mechanisms underlying arenavirus nAb evasion we engineered several arenavirus envelope-chimeric viruses and glycan-deficient variants thereof. We performed neutralization tests with sera from experimentally infected mice and from LASV-convalescent human patients. NAb response kinetics in mice correlated inversely with the N-linked glycan density in the arenavirus envelope protein's globular head. Additionally and most intriguingly, infection with fully glycosylated viruses elicited antibodies, which neutralized predominantly their glycan-deficient variants, both in mice and humans. Binding studies with monoclonal antibodies indicated that envelope glycans reduced nAb on-rate, occupancy and thereby counteracted virus neutralization. In infected mice, the envelope glycan shield promoted protracted viral infection by preventing its timely elimination by the ensuing antibody response. Thus, arenavirus envelope glycosylation impairs the protective efficacy rather than the induction of nAbs, and thereby prevents efficient antibody-mediated virus control. This immune evasion mechanism imposes limitations on antibody-based vaccination and convalescent serum therapy.

  18. Short Communication: Neutralizing Antibodies in HIV-1-Infected Brazilian Individuals

    Science.gov (United States)

    Morgado, Mariza Gonçalvez; Côrtes, Fernanda Heloise; Guimarães, Monick Lindermeyer; Mendonça-Lima, Leila; Pilotto, Jose Henrique; Grinsztejn, Beatriz; Veloso, Valdiléa Gonçalves; Bongertz, Vera

    2013-01-01

    Abstract Tests for the detection of the humoral immune response to HIV-1 have to be standardized and established, demanding regional efforts. For this purpose the neutralizing antibody (NAb) assay for HIV-1 in TZM-bl cells was introduced in Brazil. Twenty plasma samples from HIV-1-infected individuals were assayed: 10 progressors and 10 long-term nonprogressors. These were tested against eight env-pseudotyped viruses (psVs) in the TZM-bl NAb assay and against HIV-1 strain HTLV/IIIB (HIV-1 IIIB) in primary lymphocytes. Forty-four percent of the samples showed neutralizing titers for psVs and 55% for HIV-1 IIIB. Plasma from progressors showed a broader neutralization and a higher potency. The introduction of these reference reagents encourages the participation of Brazil in future comparative assessments of anti-HIV-1 antibodies. PMID:23145941

  19. Automated facial coding software outperforms people in recognizing neutral faces as neutral from standardized datasets

    NARCIS (Netherlands)

    Lewinski, P.

    2015-01-01

    Little is known about people’s accuracy of recognizing neutral faces as neutral. In this paper, I demonstrate the importance of knowing how well people recognize neutral faces. I contrasted human recognition scores of 100 typical, neutral front-up facial images with scores of an arguably objective j

  20. ORNL positive ion neutral beam program

    Energy Technology Data Exchange (ETDEWEB)

    Whealton, J.H.; Haselton, H.H.; Barber, G.C.

    1978-01-01

    The neutral beam group at Oak Ridge National Laboratory has constructed neutral beam generators for the ORMAK and PLT devices, is presently constructing neutral beam devices for the ISX and PDX devices, and is contemplating the construction of neutral beam systems for the advanced TNS device. These neutral beam devices stem from the pioneering work on ion sources of G. G. Kelley and O. B. Morgan. We describe the ion sources under development at this Laboratory, the beam optics exhibited by these sources, as well as some theoretical considerations, and finally the remainder of the beamline design.

  1. Antigens of Borrelia burgdorferi recognized during Lyme disease. Appearance of a new immunoglobulin M response and expansion of the immunoglobulin G response late in the illness.

    Science.gov (United States)

    Craft, J E; Fischer, D K; Shimamoto, G T; Steere, A C

    1986-01-01

    Using immunoblots, we identified proteins of Borrelia burgdorferi bound by IgM and IgG antibodies during Lyme disease. In 12 patients with early disease alone, both the IgM and IgG responses were restricted primarily to a 41-kD antigen. This limited response disappeared within several months. In contrast, among six patients with prolonged illness, the IgM response to the 41-kD protein sometimes persisted for months to years, and late in the illness during arthritis, a new IgM response sometimes developed to a 34-kD component of the organism. The IgG response in these patients appeared in a characteristic sequential pattern over months to years to as many as 11 spirochetal antigens. The appearance of a new IgM response and the expansion of the IgG response late in the illness, and the lack of such responses in patients with early disease alone, suggest that B. burgdorferi remains alive throughout the illness. Images PMID:3531237

  2. Serological Diagnosis of Acute Scrub Typhus in Southern India: Evaluation of InBios Scrub Typhus Detect IgM Rapid Test and Comparison with other Serological Tests.

    Science.gov (United States)

    Anitharaj, Velmurugan; Stephen, Selvaraj; Pradeep, Jothimani; Park, Sungman; Kim, Seung-Han; Kim, Young Jin; Kim, Eun-Ye; Kim, Yoon-Won

    2016-11-01

    Scrub Typhus (ST) is being reported from different parts of India in the recent past. However, the diagnosis and confirmation of ST cases require specific serological and molecular diagnostic tests. Both rapid and conventional ELISA tests need to be properly evaluated. Evaluation of a new ST IgM Immunochromatography (ICT) test kit (InBios Scrub Typhus Detect IgM Rapid Test) and compare it with another rapid kit, conventional ELISA kit and Weil-Felix (WF) test. This prospective study was carried out in Mahatma Gandhi Medical College and Research Institute, Puducherry, during November 2015 to June 2016. Clinically suspected 220 ST patients were examined by a new kit, InBios Scrub Typhus Detect IgM Rapid Test, taking the conventional InBios Scrub Typhus Detect IgM ELISA as reference. Additional comparison was made with ImmuneMed Scrub Typhus Rapid, and WF test (single OXK titers ≥1:320). Statistical analysis was performed (Chi-square, Spearman's correlation and Kappa) using IBM SPSS Statistics 17 for Windows (SPSS Inc; Chicago, USA). Percentage Sensitivity, Specificity, Positive Predictive and Negative Predictive Values for InBios, ImmuneMed and WF were 99.25, 93.02, 95.68, 98.77; 94.87, 94.19, 96.21, 92.05 and 50.38, 95.51, 94.29, 56.67 respectively. A total of 134 patients were positive in reference standard InBios IgM ELISA. This new rapid ST IgM kit validated for the first time in India, showed good sensitivity and specificity. As a Point-of-Care (PoC) test, the kit would be helpful in both urban and remote rural parts of India.

  3. Evaluation of commercially available diagnostic tests for the detection of dengue virus NS1 antigen and anti-dengue virus IgM antibody.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Hunsperger

    2014-10-01

    Full Text Available Commercially available diagnostic test kits for detection of dengue virus (DENV non-structural protein 1 (NS1 and anti-DENV IgM were evaluated for their sensitivity and specificity and other performance characteristics by a diagnostic laboratory network developed by World Health Organization (WHO, the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR and the Pediatric Dengue Vaccine Initiative (PDVI. Each network laboratory contributed characterized serum specimens for the panels used in the evaluation. Microplate enzyme-linked immunosorbent assay (ELISA and rapid diagnostic test (RDT formats were represented by the kits. Each ELISA was evaluated by 2 laboratories and RDTs were evaluated by at least 3 laboratories. The reference tests for IgM anti-DENV were laboratory developed assays produced by the Armed Forces Research Institute for Medical Science (AFRIMS and the Centers for Disease Control and Prevention (CDC, and the NS1 reference test was reverse transcriptase polymerase chain reaction (RT-PCR. Results were analyzed to determine sensitivity, specificity, inter-laboratory and inter-reader agreement, lot-to-lot variation and ease-of-use. NS1 ELISA sensitivity was 60-75% and specificity 71-80%; NS1 RDT sensitivity was 38-71% and specificity 76-80%; the IgM anti-DENV RDTs sensitivity was 30-96%, with a specificity of 86-92%, and IgM anti-DENV ELISA sensitivity was 96-98% and specificity 78-91%. NS1 tests were generally more sensitive in specimens from the acute phase of dengue and in primary DENV infection, whereas IgM anti-DENV tests were less sensitive in secondary DENV infections. The reproducibility of the NS1 RDTs ranged from 92-99% and the IgM anti-DENV RDTs from 88-94%.

  4. Evaluation of Commercially Available Diagnostic Tests for the Detection of Dengue Virus NS1 Antigen and Anti-Dengue Virus IgM Antibody

    Science.gov (United States)

    Hunsperger, Elizabeth A.; Yoksan, Sutee; Buchy, Philippe; Nguyen, Vinh Chau; Sekaran, Shamala Devi; Enria, Delia A.; Vazquez, Susana; Cartozian, Elizabeth; Pelegrino, Jose L.; Artsob, Harvey; Guzman, Maria G.; Olliaro, Piero; Zwang, Julien; Guillerm, Martine; Kliks, Susie; Halstead, Scott; Peeling, Rosanna W.; Margolis, Harold S.

    2014-01-01

    Commercially available diagnostic test kits for detection of dengue virus (DENV) non-structural protein 1 (NS1) and anti-DENV IgM were evaluated for their sensitivity and specificity and other performance characteristics by a diagnostic laboratory network developed by World Health Organization (WHO), the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) and the Pediatric Dengue Vaccine Initiative (PDVI). Each network laboratory contributed characterized serum specimens for the panels used in the evaluation. Microplate enzyme-linked immunosorbent assay (ELISA) and rapid diagnostic test (RDT formats) were represented by the kits. Each ELISA was evaluated by 2 laboratories and RDTs were evaluated by at least 3 laboratories. The reference tests for IgM anti-DENV were laboratory developed assays produced by the Armed Forces Research Institute for Medical Science (AFRIMS) and the Centers for Disease Control and Prevention (CDC), and the NS1 reference test was reverse transcriptase polymerase chain reaction (RT-PCR). Results were analyzed to determine sensitivity, specificity, inter-laboratory and inter-reader agreement, lot-to-lot variation and ease-of-use. NS1 ELISA sensitivity was 60–75% and specificity 71–80%; NS1 RDT sensitivity was 38–71% and specificity 76–80%; the IgM anti-DENV RDTs sensitivity was 30–96%, with a specificity of 86–92%, and IgM anti-DENV ELISA sensitivity was 96–98% and specificity 78–91%. NS1 tests were generally more sensitive in specimens from the acute phase of dengue and in primary DENV infection, whereas IgM anti-DENV tests were less sensitive in secondary DENV infections. The reproducibility of the NS1 RDTs ranged from 92-99% and the IgM anti-DENV RDTs from 88–94%. PMID:25330157

  5. [[Virus-like particle-based immunoglobulin M capture enzyme-linked immunosorbent assay for the detection of IgM antibodies against Chikungunya virus].

    Science.gov (United States)

    Li, Jian-dong; Zhang, Quan-fu; Zhang, Shuo; Li, Chuan; Liu, Qin-zhi; Liang, Mi-fang; Li, De-xin

    2014-11-01

    To establish a MacELISA method for the detection of IgM antibodies against Chikungunya virus (CHIKV), we prepared virus like particle (VLP) antigens of CHIKV using the whole structural protein C-E3-E2-6K-E1 encoding gene with a baculovirus expression system in Sf9 insect cells. The VLPs were purified and used to immunize Kunming mice. Then, polyclonal antibodies were purified from the samples of ascites with a protein G HiTrap SP column and labeled with horseradish peroxidase. A MacELISA method for the detection of IgM antibodies against CHIKV was assembled with goat anti-human IgM antibody, VLP antigens and an enzyme-labeled polyclonal antibody. The results were evaluated with a serum panel containing serum samples from laboratory-confirmed CHIK, HFRS patients, healthy donors, and commercially available CHIKV IgM as a quality control. It was shown that the MacELISA had a specificity of 99% (99/100), the coefficients of variation (CoV) within a plate were ELISA plates in terms of the plate variation coefficient was <15%. A comparative analysis was performed to compare the current method against a commercial CHIKV IgM antibody detection kit for IIFA-IgM. The detection limit of MacELISA was significantly lower than that of the IIFA-IgM commercial kit (P< 0.0001). Here, we demonstrate that the VLP-based MacELISA is a promising tool for the early diagnosis and epidemiological investigation of CHIKV infection, with a high level of sensitivity and specificity for the detection of IgM antibodies against CHIKV.

  6. The IgG and IgM isotypes of anti-annexin A5 antibodies: relevance for primary antiphospholipid syndrome.

    Science.gov (United States)

    Bećarević, Mirjana

    2016-11-01

    Antiphospholipid syndrome (APS) is an autoimmune disease that is characterized by the presence of thromboses and/or recurrent pregnancy losses (RPL). The persistent presence of antiphospholipid antibodies (aPL Abs): IgG and/or IgM isotypes of the anticardiolipin and/or anti-β2 glycoprotein I antibodies and lupus anticoagulant is mandatory for the laboratory diagnosis of APS. Due to the heating debate on the relevance of the IgM isotype of aPL Abs as a laboratory criterion defining APS, the focus of this article was to analyze whether both the IgG and IgM isotype of anti-annexin A5 Abs have equal relevance for clinical and serological features of patients with primary APS (PAPS). The IgG isotype of anti-annexin A5 Abs is associated with RPL in PAPS patients, although it is not elucidated whether these Abs are the cause or the consequence of RPL in PAPS. No data that could substantiate the association of the IgG and/or the IgM isotypes of anti-annexin A5 Abs with the presence of arterial and/or venous thromboses and/or their main complications in PAPS is available so far. However, the presence of clinical manifestations of the PAPS is increasing with the multiple positivity for aPL Abs and the IgM isotype of anti-annexin A5 Abs. The importance of the IgM isotype of anti-annexin A5 Abs in PAPS needs further elucidation due to the facts that majority of the available articles did not differentiate between both isotypes or only investigated the IgG isotype of anti-annexin A5 Abs.

  7. Diagnostic Performance of Five Assays for Anti-Hepatitis E Virus IgG and IgM in a Large Cohort Study

    Science.gov (United States)

    Karlsson, Marie; Mellgren, Åsa; Konar, Jan; Sandberg, Elisabeth; Lasson, Anders; Castedal, Maria; Magnius, Lars; Lagging, Martin

    2015-01-01

    Determination of anti-hepatitis E virus (anti-HEV) antibodies is still enigmatic. There is no gold standard, and results obtained with different assays often diverge. Herein, five assays were compared for detection of anti-HEV IgM and IgG. Serum samples from 500 Swedish blood donors and 316 patients, of whom 136 had suspected HEV infection, were analyzed. Concordant results for IgM and IgG with all assays were obtained only for 71% and 70% of patients with suspected hepatitis E, respectively. The range of sensitivity for anti-HEV detection was broad (42% to 96%); this was reflected in the detection limit, which varied up to 19-fold for IgM and 17-fold for IgG between assays. HEV RNA was analyzed in all patients and in those blood donors reactive for anti-HEV in any assay, and it was found in 26 individuals. Among all of the assays, both anti-HEV IgG and IgM were detected in 10 of those individuals. Twelve had only IgG and, in 7 of those 12, IgG was only detected with the two most sensitive assays. Three of the HEV-RNA-positive samples were negative for anti-HEV IgM and IgG in all assays. With the two most sensitive assays, anti-HEV IgG was identified in 16% of the blood donor samples and in 66% of patients with suspected HEV infection. Because several HEV-RNA-positive samples had only anti-HEV IgG without anti-HEV IgM or lacked anti-HEV antibodies, analysis for HEV RNA may be warranted as a complement in the laboratory diagnosis of ongoing HEV infection. PMID:26659210

  8. Lipopolysaccharide Neutralization by Cationic-Amphiphilic Polymers through Pseudoaggregate Formation.

    Science.gov (United States)

    Uppu, Divakara S S M; Haldar, Jayanta

    2016-03-14

    Synthetic polymers incorporating the cationic charge and hydrophobicity to mimic the function of antimicrobial peptides (AMPs) have been developed. These cationic-amphiphilic polymers bind to bacterial membranes that generally contain negatively charged phospholipids and cause membrane disintegration resulting in cell death; however, cationic-amphiphilic antibacterial polymers with endotoxin neutralization properties, to the best of our knowledge, have not been reported. Bacterial endotoxins such as lipopolysaccharide (LPS) cause sepsis that is responsible for a great amount of mortality worldwide. These cationic-amphiphilic polymers can also bind to negatively charged and hydrophobic LPS and cause detoxification. Hence, we envisaged that cationic-amphiphilic polymers can have both antibacterial as well as LPS binding properties. Here we report synthetic amphiphilic polymers with both antibacterial as well as endotoxin neutralizing properties. Levels of proinflammatory cytokines in human monocytes caused by LPS stimulation were inhibited by >80% when coincubated with these polymers. These reductions were found to be dependent on concentration and, more importantly, on the side-chain chemical structure due to variations in the hydrophobicity profiles of these polymers. These cationic-amphiphilic polymers bind and cause LPS neutralization and detoxification. Investigations of polymer interaction with LPS using fluorescence spectroscopy and dynamic light scattering (DLS) showed that these polymers bind but neither dissociate nor promote LPS aggregation. We show that polymer binding to LPS leads to sort of a pseudoaggregate formation resulting in LPS neutralization/detoxification. These findings provide an unusual mechanism of LPS neutralization using novel synthetic cationic-amphiphilic polymers.

  9. ¿Es necesario investigar anticuerpos IgM contra el virus de la hepatitis A cuando el enzimograma hepático es normal? Is it necessary to investigate anti-hepatitis A virus (HAV IgM antibodies when the hepatic enzymogram is normal?

    Directory of Open Access Journals (Sweden)

    C. Coitinho

    2007-09-01

    Full Text Available La hepatitis por virus A (VHA es la más frecuente de las hepatitis virales en el mundo, especialmente en los países subdesarrollados. Donde esta enfermedad es endémica, se suelen realizar un gran número de estudios de laboratorio para confirmarla. El objetivo del presente trabajo fue evaluar la utilidad de investigar anticuerpos IgM anti hepatitis A (IgM anti-VHA para el diagnóstico de la VHA en pacientes con niveles séricos normales de aspartato y alanina aminotransferasas (AST/ALT. Todos los pacientes que concurrieron al laboratorio con solicitud de enzimograma hepático y anticuerpos IgM anti-VHA durante el período octubre 2005-marzo 2006 fueron evaluados en este estudio. Los datos clínicos más frecuentes fueron presunción de hepatitis e ictericia (27,5 y 12,7%. La determinación de IgM anti-VHA se realizó por ensayo inmunoenzimático de micropartículas (MEIA; la de enzimas hepáticas en un multianalizador. De los 158 pacientes estudiados, 84 tenían valores elevados de AST/ALT; dentro de este grupo, el 82% fue reactivo para IgM anti-VHA. Los 74 pacientes restantes mostraron niveles normales de AST/ALT y solo 7 de ellos, bajo control de evolución por VHA ya confirmada, fueron reactivos para IgM anti-VHA. El 49% de los pacientes IgM anti-VHA reactivos correspondió a menores de 10 años. De acuerdo con estas observaciones, sugerimos que los estudios de laboratorio para confirmar infección aguda por VHA deberían realizarse en forma secuencial, ya que es innecesaria la determinación de anticuerpos IgM anti-VHA cuando las aminotransferasas séricas son normales.Type A viral Hepatitis (HAV is the most frequent viral hepatitis around the world, especially in low income countries. In order to confirm this disease, a lot of laboratory tests are annually carried out where HAV is endemic. Our objective was to establish the utility of investigating anti-hepatitis A virus (HAV IgM antibodies for HAV diagnosis in patients with normal

  10. ¿Es necesario investigar anticuerpos IgM contra el virus de la hepatitis A cuando el enzimograma hepático es normal?

    Directory of Open Access Journals (Sweden)

    C. Coitinho

    Full Text Available La hepatitis por virus A (VHA es la más frecuente de las hepatitis virales en el mundo, especialmente en los países subdesarrollados. Donde esta enfermedad es endémica, se suelen realizar un gran número de estudios de laboratorio para confirmarla. El objetivo del presente trabajo fue evaluar la utilidad de investigar anticuerpos IgM anti hepatitis A (IgM anti-VHA para el diagnóstico de la VHA en pacientes con niveles séricos normales de aspartato y alanina aminotransferasas (AST/ALT. Todos los pacientes que concurrieron al laboratorio con solicitud de enzimograma hepático y anticuerpos IgM anti-VHA durante el período octubre 2005-marzo 2006 fueron evaluados en este estudio. Los datos clínicos más frecuentes fueron presunción de hepatitis e ictericia (27,5 y 12,7%. La determinación de IgM anti-VHA se realizó por ensayo inmunoenzimático de micropartículas (MEIA; la de enzimas hepáticas en un multianalizador. De los 158 pacientes estudiados, 84 tenían valores elevados de AST/ALT; dentro de este grupo, el 82% fue reactivo para IgM anti-VHA. Los 74 pacientes restantes mostraron niveles normales de AST/ALT y solo 7 de ellos, bajo control de evolución por VHA ya confirmada, fueron reactivos para IgM anti-VHA. El 49% de los pacientes IgM anti-VHA reactivos correspondió a menores de 10 años. De acuerdo con estas observaciones, sugerimos que los estudios de laboratorio para confirmar infección aguda por VHA deberían realizarse en forma secuencial, ya que es innecesaria la determinación de anticuerpos IgM anti-VHA cuando las aminotransferasas séricas son normales.

  11. Diagnostic Performance of Five Assays for Anti-Hepatitis E Virus IgG and IgM in a Large Cohort Study

    OpenAIRE

    Norder, Heléne; Karlsson, Marie; Mellgren, Åsa; Konar, Jan; Sandberg, Elisabeth; Lasson, Anders; Castedal, Maria; Magnius, Lars; Lagging, Martin

    2016-01-01

    Determination of anti-hepatitis E virus (anti-HEV) antibodies is still enigmatic. There is no gold standard, and results obtained with different assays often diverge. Herein, five assays were compared for detection of anti-HEV IgM and IgG. Serum samples from 500 Swedish blood donors and 316 patients, of whom 136 had suspected HEV infection, were analyzed. Concordant results for IgM and IgG with all assays were obtained only for 71% and 70% of patients with suspected hepatitis E, respectively....

  12. Evaluation of IgM ELISA using a sonicate and a lipopolysaccharide antigen for the serodiagnosis of melioidosis

    Directory of Open Access Journals (Sweden)

    Anandan S

    2010-01-01

    Full Text Available Melioidosis, caused by Burkholderia pseudomallei, has variable manifestations. The disease can present as an acute or a chronic form or localized or disseminated or can remain latent for many years. Acute septicaemic melioidosis has a high fatality rate when untreated and therefore, an early diagnosis is critical. Lack of testing facilities and of an awareness of the manifestations of the disease makes it likely that it is underreported in India. A sonicate and a lipopolysaccharide (LPS antigen were evaluated by an IgM enzyme immunoassay in patients with culture-confirmed melioidosis (n = 29, fever of unknown origin (n = 214 and healthy controls (n = 109. Patients with melioidosis had significantly higher optical density values than both control categories, but the sensitivity of both tests was low (25% for sonicate, 62% for LPS. These data highlight the problems with serodiagnosis in endemic settings, where high cut-off values are required for specificity, and result in low sensitivity.

  13. Geology without national boundaries The 1:5 Million International Geological Map of Europe and Adjacent Areas—IGME 5000

    Institute of Scientific and Technical Information of China (English)

    Kristine Asch

    2006-01-01

    @@ The International Geological Map of Europe and Adjacent Areas (IGME 5000) is a major European geological GIS project being managed and implemented by the German Geological Survey (Federal Institute for Geosciences and Natural Resources, BGR) under the umbrella of the Commission for the Geological Map of the World (CGMW). It is a collaborative European project that to date involves 48 Geological Surveys and is supported by a network of scientific advisors. The original aims of the project have now been achieved: to develop a Geographic Information System (GIS) containing up-to-date harmonised lithological and geochronological data of Europe, and to print a geological map (Figure 1) of the preQuaternary on-shore and, for the first time at this scale, off-shore areas of Europe (see Asch, 2003, for a full account.)

  14. Evidence of fibrinogen as a target of citrullination in IgM rheumatoid factor-positive polyarticular juvenile idiopathic arthritis

    Directory of Open Access Journals (Sweden)

    Dehlendorf Amanda B

    2011-03-01

    Full Text Available Abstract Background Several studies have noted the significance of measuring anti-cyclic citrullinated peptide (CCP antibodies in juvenile idiopathic arthritis (JIA as an important indicator for destructive disease, as is the case in rheumatoid arthritis (RA. While the role of anti-CCP antibodies in RA and JIA has become better understood, the identity of the target proteins of this modification has remained elusive. In this study, we evaluated serum from patients with various subtypes of JIA to investigate the presence of anti-deiminated (citrullinated fibrinogen and anti-citrullinated α-enolase antibodies, and their association with RF and anti-CCP antibody isotypes. Methods Sera were obtained from 96 JIA patients, 19 systemic lupus erythematosus (SLE patients, and 10 healthy children. All sera were measured for antibodies against citrullinated and native fibrinogen and α-enolase by an enzyme linked immunosorbent assay (ELISA. In addition, all sera were assayed for anti-CCP antibody isotypes and rheumatoid factor (RF isotypes by ELISA. The relationship between anti-citrullinated fibrinogen and anti-α-enolase antibodies and disease activity and joint damage were also investigated. All results were correlated with clinical and laboratory parameters using Spearman's rho correlation coefficient. Multiple logistic regression analysis was utilized to identify which variables were associated with joint erosions and diagnosis of JIA. Results Thirty-one JIA patients (32% demonstrated reactivity to citrullinated fibrinogen and 9 (9% to citrullinated α-enolase. Reactivity to citrullinated fibrinogen and α-enolase was predominantly found in IgM RF-positive polyarthritis patients. Fourteen JIA patients reacted with native α-enolase and a higher percentage of SLE patients reacted with citrullinated α-enolase when compared to JIA patients. Anti-citrullinated fibrinogen antibodies correlated with the presence of IgG anti-CCP antibodies and IgA and IgM

  15. IgM antibodies to N-acetylgalactosaminyl GD1a in benign monomelic amyotrophy of the lower limb.

    Science.gov (United States)

    Weiss, Michael D

    2005-08-15

    A male Caucasian patient is presented with a greater than 10-year history of painless weakness of the right leg, stable over the last 7 years. His examination demonstrated severe wasting and moderate weakness of his right calf muscle. Electrodiagnostic study revealed acute denervation of the right calf and chronic partial denervation of multiple right leg muscles. MRI demonstrated atrophy and fatty infiltration of the right calf muscles. Based on previous clinical, electrophysiologic, and radiologic descriptions of this disorder, a diagnosis was made of benign monomelic amyotrophy of the lower limb. Serologic examination for anti-glycoconjugate antibodies revealed high titers of IgM antibodies with selective binding to the disialoganglioside N-acetylgalactosaminyl GD1a (GalNAcGD1a). Testing for antibodies to GalNAcGD1a should be considered in patients with this phenotype. Their presence could suggest a role for immunomodulatory therapy.

  16. A truncated receptor-binding domain of MERS-CoV spike protein potently inhibits MERS-CoV infection and induces strong neutralizing antibody responses: implication for developing therapeutics and vaccines.

    Directory of Open Access Journals (Sweden)

    Lanying Du

    Full Text Available An emerging respiratory infectious disease with high mortality, Middle East respiratory syndrome (MERS, is caused by a novel coronavirus (MERS-CoV. It was first reported in 2012 in Saudi Arabia and has now spread to eight countries. Development of effective therapeutics and vaccines is crucial to save lives and halt the spread of MERS-CoV. Here, we show that a recombinant protein containing a 212-amino acid fragment (residues 377-588 in the truncated receptor-binding domain (RBD: residues 367-606 of MERS-CoV spike (S protein fused with human IgG Fc fragment (S377-588-Fc is highly expressed in the culture supernatant of transfected 293T cells. The purified S377-588-Fc protein efficiently binds to dipeptidyl peptidase 4 (DPP4, the receptor of MERS-CoV, and potently inhibited MERS-CoV infection, suggesting its potential to be further developed as a therapeutic modality for treating MERS-CoV infection and saving the patients' lives. The recombinant S377-588-Fc is able to induce in the vaccinated mice strong MERS-CoV S-specific antibodies, which blocks the binding of RBD to DPP4 receptor and effectively neutralizes MERS-CoV infection. These findings indicate that this truncated RBD protein shows promise for further development as an effective and safe vaccine for the prevention of MERS-CoV infection.

  17. Measuring Alignments between Galaxies and the Cosmic Web at z ˜ 2-3 Using IGM Tomography

    Science.gov (United States)

    Krolewski, Alex; Lee, Khee-Gan; Lukić, Zarija; White, Martin

    2017-03-01

    Many galaxy formation models predict alignments between galaxy spin and the cosmic web (i.e., directions of filaments and sheets), leading to an intrinsic alignment between galaxies that creates a systematic error in weak-lensing measurements. These effects are often predicted to be stronger at high redshifts (z ≳ 1) that are inaccessible to massive galaxy surveys on foreseeable instrumentation, but IGM tomography of the Lyα forest from closely spaced quasars and galaxies is starting to measure the z ˜ 2-3 cosmic web with requisite fidelity. Using mock surveys from hydrodynamical simulations, we examine the utility of this technique, in conjunction with coeval galaxy samples, to measure alignment between galaxies and the cosmic web at z ˜ 2.5. We show that IGM tomography surveys with ≲5 h -1 Mpc sightline spacing can accurately recover the eigenvectors of the tidal tensor, which we use to define the directions of the cosmic web. For galaxy spins and shapes, we use a model parameterized by the alignment strength, {{Δ }} , with respect to the tidal tensor eigenvectors from the underlying density field, and also consider observational effects such as errors in the galaxy position angle, inclination, and redshift. Measurements using the upcoming ˜1 deg2 CLAMATO tomographic survey and 600 coeval zCOSMOS-Deep galaxies should place 3σ limits on extreme alignment models with {{Δ }} ˜ 0.1, but much larger surveys encompassing >10,000 galaxies, such as Subaru PFS, will be required to constrain models with {{Δ }} ˜ 0.03. These measurements will constrain models of galaxy-cosmic web alignment and test tidal torque theory at z ˜ 2, improving our understanding of the physics of intrinsic alignments.

  18. Plasma exchange and chlorambucil in polyneuropathy associated with monoclonal IgM gammopathy. IgM-associated Polyneuropathy Study Group.

    Science.gov (United States)

    Oksenhendler, E; Chevret, S; Léger, J M; Louboutin, J P; Bussel, A; Brouet, J C

    1995-01-01

    The study compared chlorambucil alone with chlorambucil in combination with plasma exchange in patients with polyneuropathy associated with monoclonal IgM. Forty four patients were prospectively randomly assigned, in a comparative open trial, to receive either 0.1 mg/kg/day chlorambucil orally, for 12 months or chlorambucil associated with 15 courses of plasma exchange, during the first four months of treatment. They were evaluated by a neuropathy disability score and nerve conduction studies. No difference was found between the two treatment groups. The average neuropathy disability score improved by 2.1 points from baseline (21.0 to 18.9) in the chlorambucil group and by 1.8 points (20.4 to 18.6) in the chlorambucil + plasma exchange group (P = 0.70). The mean motor nerve conduction velocity decreased from 20.0 to 18.2 m/s in the chlorambucil group and increased from 20.5 to 22.5 m/s in the chlorambucil + plasma exchange group (P = 0.51). A slight improvement of the sensory component of the neuropathy disability score (from 10.5 to 8.3) was noted in both groups (P = 0.01). At the end of the study and according to self evaluation, 15 patients--eight from the chlorambucil group and seven from the chlorambucil + plasma exchange group--reported clinical improvement, whereas 15--eight from the chlorambucil group and seven from the chlorambucil + plasma exchange group--reported clinical worsening. Neuropathy remained stable in the others. Thus plasma exchange seemed to confer no additional benefit in the treatment of polyneuropathy associated with monoclonal IgM. PMID:7673949

  19. Generation of human antigen-specific monoclonal IgM antibodies using vaccinated "human immune system" mice.

    Directory of Open Access Journals (Sweden)

    Pablo D Becker

    Full Text Available BACKGROUND: Passive transfer of antibodies not only provides immediate short-term protection against disease, but also can be exploited as a therapeutic tool. However, the 'humanization' of murine monoclonal antibodies (mAbs is a time-consuming and expensive process that has the inherent drawback of potentially altering antigenic specificity and/or affinity. The immortalization of human B cells represents an alternative for obtaining human mAbs, but relies on the availability of biological samples from vaccinated individuals or convalescent patients. In this work we describe a novel approach to generate fully human mAbs by combining a humanized mouse model with a new B cell immortalization technique. METHODOLOGY/PRINCIPAL FINDINGS: After transplantation with CD34+CD38⁻ human hematopoietic progenitor cells, BALB/c Rag2⁻/⁻IL-2Rγc⁻/⁻ mice acquire a human immune system and harbor B cells with a diverse IgM repertoire. "Human Immune System" mice were then immunized with two commercial vaccine antigens, tetanus toxoid and hepatitis B surface antigen. Sorted human CD19+CD27+ B cells were retrovirally transduced with the human B cell lymphoma (BCL-6 and BCL-XL genes, and subsequently cultured in the presence of CD40-ligand and IL-21. This procedure allows generating stable B cell receptor-positive B cells that secrete immunoglobulins. We recovered stable B cell clones that produced IgM specific for tetanus toxoid and the hepatitis B surface antigen, respectively. CONCLUSION/SIGNIFICANCE: This work provides the proof-of-concept for the usefulness of this novel method based on the immunization of humanized mice for the rapid generation of human mAbs against a wide range of antigens.

  20. A natural human IgM that binds to gangliosides is therapeutic in murine models of amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Xiaohua Xu

    2015-08-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a devastating, fatal neurological disease that primarily affects spinal cord anterior horn cells and their axons for which there is no treatment. Here we report the use of a recombinant natural human IgM that binds to the surface of neurons and supports neurite extension, rHIgM12, as a therapeutic strategy in murine models of human ALS. A single 200 µg intraperitoneal dose of rHIgM12 increases survival in two independent genetic-based mutant SOD1 mouse strains (SOD1G86R and SOD1G93A by 8 and 10 days, delays the onset of neurological deficits by 16 days, delays the onset of weight loss by 5 days, and preserves spinal cord axons and anterior horn neurons. Immuno-overlay of thin layer chromatography and surface plasmon resonance show that rHIgM12 binds with high affinity to the complex gangliosides GD1a and GT1b. Addition of rHIgM12 to neurons in culture increases α-tubulin tyrosination levels, suggesting an alteration of microtubule dynamics. We previously reported that a single peripheral dose of rHIgM12 preserved neurological function in a murine model of demyelination with axon loss. Because rHIgM12 improves three different models of neurological disease, we propose that the IgM might act late in the cascade of neuronal stress and/or death by a broad mechanism.

  1. Neutral hydrogen and magnetic fields in M83 observed with the SKA Pathfinder KAT-7

    CERN Document Server

    Heald, G; Lucero, D; Carignan, C; Jarrett, T; Elson, E; Oozeer, N; Randriamampandry, T H; van Zee, L

    2016-01-01

    We present new KAT-7 observations of the neutral hydrogen (HI) spectral line, and polarized radio continuum emission, in the grand design spiral M83. These observations provide a sensitive probe of the outer disk structure and kinematics, revealing a vast and massive neutral gas distribution that appears to be tightly coupled to the interaction of the galaxy with the environment. We present a new rotation curve extending out to a radius of 50 kpc. Based on our new HI dataset and comparison with multiwavelength data from the literature we consider the impact of mergers on the outer disk and discuss the evolution of M83. We also study the periphery of the HI distribution and reveal a sharp edge to the gaseous disk that is consistent with photoionization or ram pressure from the intergalactic medium (IGM). The radio continuum emission is not nearly as extended as the HI and is restricted to the main optical disk. Despite the relatively low angular resolution we are able to draw broad conclusions about the large-...

  2. Neutral red-mediated microbial electrosynthesis by Escherichia coli, Klebsiella pneumoniae, and Zymomonas mobilis.

    Science.gov (United States)

    Harrington, Timothy D; Mohamed, Abdelrhman; Tran, Vi N; Biria, Saeid; Gargouri, Mahmoud; Park, Jeong-Jin; Gang, David R; Beyenal, Haluk

    2015-11-01

    The aim of this work was to compare the effects of electrosynthesis on different bacterial species. The effects of neutral red-mediated electrosynthesis on the metabolite profiles of three microorganisms: Escherichia coli, Klebsiella pneumoniae, and Zymomonas mobilis, were measured and compared and contrasted. A statistically comprehensive analysis of neutral red-mediated electrosynthesis is presented using the analysis of end-product profiles, current delivered, and changes in cellular protein expression. K. pneumoniae displayed the most dramatic response to electrosynthesis of the three bacteria, producing 93% more ethanol and 76% more lactate vs. control fermentation with no neutral red and no electron delivery. Z. mobilis showed no response to electrosynthesis except elevated acetate titers. Stoichiometric comparison showed that NAD(+) reduction by neutral red could not account for changes in metabolites during electrosynthesis. Neutral red-mediated electrosynthesis was shown to have multifarious effects on the three species.

  3. $\\tau$ decays with neutral kaons

    CERN Document Server

    Abbiendi, G.; Akesson, P.F.; Alexander, G.; Allison, John; Anderson, K.J.; Arcelli, S.; Asai, S.; Ashby, S.F.; Axen, D.; Azuelos, G.; Bailey, I.; Ball, A.H.; Barberio, E.; Barlow, Roger J.; Batley, J.R.; Baumann, S.; Behnke, T.; Bell, Kenneth Watson; Bella, G.; Bellerive, A.; Bentvelsen, S.; Bethke, S.; Betts, S.; Biebel, O.; Biguzzi, A.; Bloodworth, I.J.; Bock, P.; Bohme, J.; Boeriu, O.; Bonacorsi, D.; Boutemeur, M.; Braibant, S.; Bright-Thomas, P.; Brigliadori, L.; Brown, Robert M.; Burckhart, H.J.; Capiluppi, P.; Carnegie, R.K.; Carter, A.A.; Carter, J.R.; Chang, C.Y.; Charlton, David G.; Chrisman, D.; Ciocca, C.; Clarke, P.E.L.; Clay, E.; Cohen, I.; Conboy, J.E.; Cooke, O.C.; Couchman, J.; Couyoumtzelis, C.; Coxe, R.L.; Cuffiani, M.; Dado, S.; Dallavalle, G.Marco; Dallison, S.; Davis, R.; de Roeck, A.; Dervan, P.; Desch, K.; Dienes, B.; Dixit, M.S.; Donkers, M.; Dubbert, J.; Duchovni, E.; Duckeck, G.; Duerdoth, I.P.; Estabrooks, P.G.; Etzion, E.; Fabbri, F.; Fanfani, A.; Fanti, M.; Faust, A.A.; Feld, L.; Ferrari, P.; Fiedler, F.; Fierro, M.; Fleck, I.; Frey, A.; Furtjes, A.; Futyan, D.I.; Gagnon, P.; Gary, J.W.; Gaycken, G.; Geich-Gimbel, C.; Giacomelli, G.; Giacomelli, P.; Gingrich, D.M.; Glenzinski, D.; Goldberg, J.; Gorn, W.; Grandi, C.; Graham, K.; Gross, E.; Grunhaus, J.; Gruwe, M.; Hajdu, C.; Hanson, G.G.; Hansroul, M.; Hapke, M.; Harder, K.; Harel, A.; Hargrove, C.K.; Harin-Dirac, M.; Hauschild, M.; Hawkes, C.M.; Hawkings, R.; Hemingway, R.J.; Herten, G.; Heuer, R.D.; Hildreth, M.D.; Hill, J.C.; Hobson, P.R.; Hocker, James Andrew; Hoffman, Kara Dion; Homer, R.J.; Honma, A.K.; Horvath, D.; Hossain, K.R.; Howard, R.; Huntemeyer, P.; Igo-Kemenes, P.; Imrie, D.C.; Ishii, K.; Jacob, F.R.; Jawahery, A.; Jeremie, H.; Jimack, M.; Jones, C.R.; Jovanovic, P.; Junk, T.R.; Kanaya, N.; Kanzaki, J.; Karapetian, G.; Karlen, D.; Kartvelishvili, V.; Kawagoe, K.; Kawamoto, T.; Kayal, P.I.; Keeler, R.K.; Kellogg, R.G.; Kennedy, B.W.; Kim, D.H.; Klier, A.; Kobayashi, T.; Kobel, M.; Kokott, T.P.; Kolrep, M.; Komamiya, S.; Kowalewski, Robert V.; Kress, T.; Krieger, P.; von Krogh, J.; Kuhl, T.; Kupper, M.; Kyberd, P.; Lafferty, G.D.; Landsman, H.; Lanske, D.; Lauber, J.; Lawson, I.; Layter, J.G.; Lellouch, D.; Letts, J.; Levinson, L.; Liebisch, R.; Lillich, J.; List, B.; Littlewood, C.; Lloyd, A.W.; Lloyd, S.L.; Loebinger, F.K.; Long, G.D.; Losty, M.J.; Lu, J.; Ludwig, J.; Macchiolo, A.; Macpherson, A.; Mader, W.; Mannelli, M.; Marcellini, S.; Marchant, T.E.; Martin, A.J.; Martin, J.P.; Martinez, G.; Mashimo, T.; Mattig, Peter; McDonald, W.John; McKenna, J.; Mckigney, E.A.; McMahon, T.J.; McPherson, R.A.; Meijers, F.; Mendez-Lorenzo, P.; Merritt, F.S.; Mes, H.; Meyer, I.; Michelini, A.; Mihara, S.; Mikenberg, G.; Miller, D.J.; Mohr, W.; Montanari, A.; Mori, T.; Nagai, K.; Nakamura, I.; Neal, H.A.; Nisius, R.; O'Neale, S.W.; Oakham, F.G.; Odorici, F.; Ogren, H.O.; Okpara, A.; Oreglia, M.J.; Orito, S.; Pasztor, G.; Pater, J.R.; Patrick, G.N.; Patt, J.; Perez-Ochoa, R.; Petzold, S.; Pfeifenschneider, P.; Pilcher, J.E.; Pinfold, J.; Plane, David E.; Poli, B.; Polok, J.; Przybycien, M.; Quadt, A.; Rembser, C.; Rick, H.; Robins, S.A.; Rodning, N.; Roney, J.M.; Rosati, S.; Roscoe, K.; Rossi, A.M.; Rozen, Y.; Runge, K.; Runolfsson, O.; Rust, D.R.; Sachs, K.; Saeki, T.; Sahr, O.; Sang, W.M.; Sarkisian, E.K.G.; Sbarra, C.; Schaile, A.D.; Schaile, O.; Scharff-Hansen, P.; Schieck, J.; Schmitt, S.; Schoning, A.; Schroder, Matthias; Schumacher, M.; Schwick, C.; Scott, W.G.; Seuster, R.; Shears, T.G.; Shen, B.C.; Shepherd-Themistocleous, C.H.; Sherwood, P.; Siroli, G.P.; Skuja, A.; Smith, A.M.; Snow, G.A.; Sobie, R.; Soldner-Rembold, S.; Spagnolo, S.; Sproston, M.; Stahl, A.; Stephens, K.; Stoll, K.; Strom, David M.; Strohmer, R.; Surrow, B.; Talbot, S.D.; Taras, P.; Tarem, S.; Teuscher, R.; Thiergen, M.; Thomas, J.; Thomson, M.A.; Torrence, E.; Towers, S.; Trefzger, T.; Trigger, I.; Trocsanyi, Z.; Tsur, E.; Turner-Watson, M.F.; Ueda, I.; Van Kooten, Rick J.; Vannerem, P.; Verzocchi, M.; Voss, H.; Wackerle, F.; Waller, D.; Ward, C.P.; Ward, D.R.; Watkins, P.M.; Watson, A.T.; Watson, N.K.; Wells, P.S.; Wengler, T.; Wermes, N.; Wetterling, D.; White, J.S.; Wilson, G.W.; Wilson, J.A.; Wyatt, T.R.; Yamashita, S.; Zacek, V.; Zer-Zion, D.

    2000-01-01

    The branching ratio of the tau lepton to a neutral K meson is measured from a sample of approximately 200,000 tau decays recorded by the OPAL detector at centre-of-mass energies near the Z0 resonance. The measurement is based on two samples which identify one-prong tau decays with KL and KS mesons. The combined branching ratios are measured to be B(tau- -->pi- K0bar nutau) = (9.33+-0.68+-0.49)x10^-3 B(tau- -->pi- K0bar [>=1pi0] nutau) = (3.24+-0.74+-0.66)x10^-3 B(tau- -->K- K0bar [>=0pi0] nutau) = (3.30+-0.55+-0.39)x10^-3 where the first error is statistical and the second systematic.

  4. Laser sputter neutral mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    King, B.V.; Clarke, M.; Hu, H.; Betz [Newcastle Univ., NSW (Australia). Dept. of Physics

    1993-12-31

    Laser sputter neutral mass spectrometry (LSNMS) is an emerging technique for highly sensitive surface analysis. In this technique a target is bombarded with a pulsed beam of keV ions. The sputtered particles are intercepted by a high intensity pulsed laser beam above the surface and ionised with almost 100% efficiency. The photions may then be mass analysed using a quadrupole or, more commonly, using time of flight (TOF) techniques. In this method photoions are extracted from the ionisation region, accelerated to a known energy E{sub o} and strike a channelplate detector a distance `d` away. The flight time `t` of the photoions is then related to their mass by `d` {radical}m / {radical} 2E{sub o} so measurement of `t` allows mass spectra to be obtained. It is found that LSNMS is an emerging technique of great sensitivity and flexibility, useful for both applied analysis and to investigate basic sputtering processes. 4 refs., 3 figs.

  5. Measuring Low Fluxes of Photons, Neutral Molecules and Ions with a New Generation of Detectors Project

    Data.gov (United States)

    National Aeronautics and Space Administration — A new detector evaluation method (DEM) is proposed to determine the response of graphene detectors to low fluxes of photons, neutral atoms/molecules, and ions in the...

  6. Primary neutral helium in the heliosphere

    CERN Document Server

    Mueller, Hans-Reinhard

    2012-01-01

    Two years of neutral measurements by IBEX-Lo have yielded several direct observations of interstellar neutral helium and oxygen during preferred viewing seasons. Besides the interstellar signal, there are indications of the presence of secondary neutral helium and oxygen created in the heliosphere. Detailed modeling of these particle species is necessary to connect the measured fluxes to the pristine local interstellar medium while accounting for loss and production of neutral particles during their path through the heliosphere. In this contribution, global heliosphere models are coupled to analytic calculations of neutral trajectories to obtain detailed estimates of the neutral distribution function of primary interstellar helium atoms in the heliosphere, in particular in the inner heliosphere.

  7. Molecular clock on a neutral network.

    Science.gov (United States)

    Raval, Alpan

    2007-09-28

    The number of fixed mutations accumulated in an evolving population often displays a variance that is significantly larger than the mean (the overdispersed molecular clock). By examining a generic evolutionary process on a neutral network of high-fitness genotypes, we establish a formalism for computing all cumulants of the full probability distribution of accumulated mutations in terms of graph properties of the neutral network, and use the formalism to prove overdispersion of the molecular clock. We further show that significant overdispersion arises naturally in evolution when the neutral network is highly sparse, exhibits large global fluctuations in neutrality, and small local fluctuations in neutrality. The results are also relevant for elucidating aspects of neutral network topology from empirical measurements of the substitution process.

  8. Agglutinating mouse IgG3 compares favourably with IgMs in typing of the blood group B antigen: Functionality and stability studies.

    Science.gov (United States)

    Klaus, Tomasz; Bzowska, Monika; Kulesza, Małgorzata; Kabat, Agnieszka Martyna; Jemioła-Rzemińska, Małgorzata; Czaplicki, Dominik; Makuch, Krzysztof; Jucha, Jarosław; Karabasz, Alicja; Bereta, Joanna

    2016-08-03

    Mouse immunoglobulins M (IgMs) that recognize human blood group antigens induce haemagglutination and are used worldwide for diagnostic blood typing. Contrary to the current belief that IgGs are too small to simultaneously bind antigens on two different erythrocytes, we obtained agglutinating mouse IgG3 that recognized antigen B of the human ABO blood group system. Mouse IgG3 is an intriguing isotype that has the ability to form Fc-dependent oligomers. However, F(ab')2 fragments of the IgG3 were sufficient to agglutinate type B red blood cells; therefore, IgG3-triggered agglutination did not require oligomerization. Molecular modelling indicated that mouse IgG3 has a larger range of Fab arms than other mouse IgG subclasses and that the unique properties of mouse IgG3 are likely due to the structure of its hinge region. With a focus on applications in diagnostics, we compared the stability of IgG3 and two IgMs in formulated blood typing reagents using an accelerated storage approach and differential scanning calorimetry. IgG3 was much more stable than IgMs. Interestingly, the rapid decrease in IgM activity was caused by aggregation of the molecules and a previously unknown posttranslational proteolytic processing of the μ heavy chain. Our data point to mouse IgG3 as a potent diagnostic tool.

  9. Agglutinating mouse IgG3 compares favourably with IgMs in typing of the blood group B antigen: Functionality and stability studies

    Science.gov (United States)

    Klaus, Tomasz; Bzowska, Monika; Kulesza, Małgorzata; Kabat, Agnieszka Martyna; Jemioła-Rzemińska, Małgorzata; Czaplicki, Dominik; Makuch, Krzysztof; Jucha, Jarosław; Karabasz, Alicja; Bereta, Joanna

    2016-01-01

    Mouse immunoglobulins M (IgMs) that recognize human blood group antigens induce haemagglutination and are used worldwide for diagnostic blood typing. Contrary to the current belief that IgGs are too small to simultaneously bind antigens on two different erythrocytes, we obtained agglutinating mouse IgG3 that recognized antigen B of the human ABO blood group system. Mouse IgG3 is an intriguing isotype that has the ability to form Fc-dependent oligomers. However, F(ab′)2 fragments of the IgG3 were sufficient to agglutinate type B red blood cells; therefore, IgG3-triggered agglutination did not require oligomerization. Molecular modelling indicated that mouse IgG3 has a larger range of Fab arms than other mouse IgG subclasses and that the unique properties of mouse IgG3 are likely due to the structure of its hinge region. With a focus on applications in diagnostics, we compared the stability of IgG3 and two IgMs in formulated blood typing reagents using an accelerated storage approach and differential scanning calorimetry. IgG3 was much more stable than IgMs. Interestingly, the rapid decrease in IgM activity was caused by aggregation of the molecules and a previously unknown posttranslational proteolytic processing of the μ heavy chain. Our data point to mouse IgG3 as a potent diagnostic tool. PMID:27484487

  10. The occurrence of IgM and complement factors along myelin sheaths of peripheral nerves An immunohistochemical study of the Guillain-Barre syndrome : Preliminary communication

    NARCIS (Netherlands)

    Luijten, J.A.F.M.; Baart de la Faille-Kuyper, E.H.

    In nerve biopsies from 4 of 6 patients with the Guillain-Barré syndrome (GBS), IgM and complement factors were found, probably localized along myelin sheaths. The possible significance of this phenomenon has been discussed. No such findings were obtained in control subjects.

  11. THE STUDIES OF SERUM CVB-SPECIFIC IgM ANTIBODY AND NITRIC OXIDE AMONG THE PATIENTS WITH LATENT AND CHRONIC KESHAN DISEASE

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To investigate the serum coxsackie virus B(CVB) infection and nitric oxide (NO)level of the patients suffer from latent or chronic Keshan disease and their characteristics in the etiopathology of Keshan disease. Methods Sera were isolated from 30 patients with latent or chronic Keshan disease in Huangling county.Shaanxi Province, and the CVB-specific IgM antibody and NO were tested. Control groups were health subjects in Huangling county or Xi'an city, Shaanxi Province. Results The percentage of CVB-specific IgM positive in patients in Huangling county was significantly higher than that of both control groups in Huangling county and Xi'an city (P<0. 05). The serum level of NO in patients was significantly higher than that of the control group in Huangling county (P<0.05) ,however,compared with control group in Xi'an city, there was no difference (P>0.05). In CVB-specific IgM positive patients,the serum level of NO was significantly higher than that of CVB-specific IgM negative group(P<0.05).Conclusion CVB infection and serum NO level might be related to the etiopathology and the development of Keshan disease.

  12. Enzyme-linked immunoassay for dengue virus IgM and IgG antibodies in serum and filter paper blood

    NARCIS (Netherlands)

    Tran, T.N.T.; de Vries, P.J.; Hoang, L.P.; Phan, G.T.; Le, H.Q.; Tran, B.Q.; Vo, C.M.T.; Nguyen, N.V.; Kager, P.A.; Nagelkerke, N.; Groen, J.

    2006-01-01

    Background: The reproducibilty of dengue IgM and IgG ELISA was studied in serum and filter paper blood spots from Vietnamese febrile patients. Methods: 781 pairs of acute (t0) and convalescent sera, obtained after three weeks (t3) and 161 corresponding pairs of filter paper blood spots were tested

  13. Cerebral toxoplasmosis after umbilical cord blood transplantation diagnosed by the detection of anti-toxoplasma specific IgM antibody in cerebrospinal fluid.

    Science.gov (United States)

    Inaba, Akiko; Koh, Hideo; Nakashima, Yasuhiro; Nishimoto, Mitsutaka; Hayashi, Yoshiki; Okamura, Hiroshi; Inoue, Atsushi; Nanno, Satoru; Nakane, Takahiko; Shimono, Taro; Nakamae, Hirohisa; Hino, Masayuki

    2014-04-01

    Cerebral toxoplasmosis is a rare, potentially fatal, complication of hematopoietic cell transplantation. Early definitive diagnosis is very difficult and it may be associated with a poor prognosis. Herein, we describe a 60-year-old woman who developed cerebral toxoplasmosis after cord blood transplantation for myelodysplastic syndrome. During treatment with tacrolimus and methylprednisolone for relapsed grade 2 acute gut GVHD, fever and disturbance of consciousness occurred on day 210. Brain MRI showed multiple ring-enhancing nodular lesions in the thalamus, basal ganglia, brainstem, and subcortical white matter. Cerebrospinal fluid (CSF) assessment revealed elevations of both anti-to-xoplasma IgM and IgG, which were also elevated in serum, but no evidence of other infections or malignancies. Notably, the IgM level was higher in the CSF than in serum. Thus, cerebral toxoplasmosis was diagnosed. Soon after administration of oral sulfamethoxazole/trimethoprim and intravenous clindamycin in combination with short-term dexamethasone for the cerebral edema, her symptoms and signs began to improve. On day 229, both IgM and IgG titers in CSF had clearly decreased but remained essentially constant in serum. She was discharged without clinically significant neurological disorders. This case suggests that CSF specific anti-toxoplasma IgM titers might be useful for early diagnosis of cerebral toxoplasmosis after transplantation.

  14. The occurrence of IgM and complement factors along myelin sheaths of peripheral nerves An immunohistochemical study of the Guillain-Barre syndrome : Preliminary communication

    NARCIS (Netherlands)

    Luijten, J.A.F.M.; Baart de la Faille-Kuyper, E.H.

    1972-01-01

    In nerve biopsies from 4 of 6 patients with the Guillain-Barré syndrome (GBS), IgM and complement factors were found, probably localized along myelin sheaths. The possible significance of this phenomenon has been discussed. No such findings were obtained in control subjects.

  15. Multiplex Detection of IgG and IgM to Rift Valley Fever Virus Nucleoprotein, Nonstructural Proteins, and Glycoprotein in Ovine and Bovine

    Science.gov (United States)

    A multiplex fluorescence microsphere immunoassay (FMIA) was used to detect bovine and ovine IgM and IgG antibodies to several Rift Valley fever virus (RVFV) proteins, including the major surface glycoprotein, Gn; the nonstructural proteins, NSs and NSm; and the nucleoprotein, N. Target antigens were...

  16. Investigating the function of Fc-specific binding of IgM to Plasmodium falciparum erythrocyte membrane protein 1 mediating erythrocyte rosetting

    DEFF Research Database (Denmark)

    Stevenson, Liz; Huda, Pie; Jeppesen, Anine;

    2015-01-01

    Acquired protection from Plasmodium falciparum malaria takes years to develop, probably reflecting the ability of the parasites to evade immunity. A recent example of this is the binding of the Fc region of IgM to VAR2CSA-type PfEMP1. This interferes with specific IgG recognition and phagocytosis...

  17. TUMOR-LOCALIZATION WITH I-131-LABELED HUMAN-IGM MONOCLONAL-ANTIBODY 16.88 IN ADVANCED COLORECTAL-CANCER PATIENTS

    NARCIS (Netherlands)

    BOVEN, E; Haisma, Hidde; BRIL, H; MARTENS, HJM; VANLINGEN, A; DENHOLLANDER, W; KESSEL, MAP; DEJAGER, RL; ROOS, JC

    1991-01-01

    Human IgM monoclonal antibody 16.88 recognised an intracellular antigen strongly expressed in colorectal cancer tissue in 51% of our patients. Tumour localisation was carried out with 185 MBq I-131-16.88 (8 mg) in 20 of these patients with advanced disease. In 16 patients (80%) immunoscintigraphy wa

  18. Immune Dysfunction in Rett Syndrome Patients Revealed by High Levels of Serum Anti-N(Glc IgM Antibody Fraction

    Directory of Open Access Journals (Sweden)

    Anna Maria Papini

    2014-01-01

    Full Text Available Rett syndrome (RTT, a neurodevelopmental disorder affecting exclusively (99% female infants, is associated with loss-of-function mutations in the gene encoding methyl-CpG binding protein 2 (MECP2 and, more rarely, cyclin-dependent kinase-like 5 (CDKL5 and forkhead box protein G1 (FOXG1. In this study, we aimed to evaluate the function of the immune system by measuring serum immunoglobulins (IgG and IgM in RTT patients (n=53 and, by comparison, in age-matched children affected by non-RTT pervasive developmental disorders (non-RTT PDD (n=82 and healthy age-matched controls (n=29. To determine immunoglobulins we used both a conventional agglutination assay and a novel ELISA based on antibody recognition by a surrogate antigen probe, CSF114(Glc, a synthetic N-glucosylated peptide. Both assays provided evidence for an increase in IgM titer, but not in IgG, in RTT patients relative to both healthy controls and non-RTT PDD patients. The significant difference in IgM titers between RTT patients and healthy subjects in the CSF114(Glc assay (P=0.001 suggests that this procedure specifically detects a fraction of IgM antibodies likely to be relevant for the RTT disease. These findings offer a new insight into the mechanism underlying the Rett disease as they unveil the possible involvement of the immune system in this pathology.

  19. Evidence for shared idiotypy expressed by the IgM, IgG, and IgA serum proteins of a patient with a complex multiple paraprotein disorder

    Energy Technology Data Exchange (ETDEWEB)

    Hopper, J.E.; Haren, J.M.; Kmiecik, T.E.

    1979-05-01

    The results of a comparative idiotypic analysis of multiple Ig paraproteins isolated from the serum of an individual patient, Ca, with Sjoegren's syndrome and Waldenstroem's macroglobulinemia are reported. At initial presentation, Ca serum was found to contain two major paraproteins, an IgMk and an IgGk, together with a small elevation in the level of IgA protein. The patient's clinical course was characterized by dramatic and opposing changes in the respective serum levels of the IgMk and IgGk paraproteins over an extended time period that coincided in part with received chemotherapy. Idiotypic antigenic analysis of the IgMk and IgGk paraproteins revealed that the two monotypic proteins shared identical idiotypic determinants. The Ca IgA serum fraction, specifically isolated by an immunoabsorbent and free of any IgG and IgM, was shown to possess idiotypic determinants identical to the IgG and IgM proteins. In extensive tests of specificity, the idiotypic determinants shared by Ca IgM, IgG, and IgA proteins were not present in large excesses of heterologous IgM and IgG, nor on Ig molecules contained in a large number of normal and myeloma sera.

  20. The occurrence of IgM and complement factors along myelin sheaths of peripheral nerves An immunohistochemical study of the Guillain-Barre syndrome : Preliminary communication

    NARCIS (Netherlands)

    Luijten, J.A.F.M.; Baart de la Faille-Kuyper, E.H.

    1972-01-01

    In nerve biopsies from 4 of 6 patients with the Guillain-Barré syndrome (GBS), IgM and complement factors were found, probably localized along myelin sheaths. The possible significance of this phenomenon has been discussed. No such findings were obtained in control subjects.

  1. Enzyme-linked immunoassay for dengue virus IgM and IgG antibodies in serum and filter paper blood

    NARCIS (Netherlands)

    T.N.T. Tran (Thanh Nga); P.J. de Vries (Peter); L.P. Hoang (Lan Phuong); G.T. Phan (Giao); H.Q. Le (Hung); B.Q. Tran (Binh); C.M.T. Vo (Chi Mai); N.V. Nguyen (Nam); P.A. Kager (Piet); N.J.D. Nagelkerke (Nico); J.M. Groen (Jan)

    2006-01-01

    textabstractBackground: The reproducibilty of dengue IgM and IgG ELISA was studied in serum and filter paper blood spots from Vietnamese febrile patients. Methods: 781 pairs of acute (t0) and convalescent sera, obtained after three weeks (t3) and 161 corresponding pairs of filter paper blood spots

  2. Analysis of Tn antigenicity with a panel of new IgM and IgG1 monoclonal antibodies raised against leukemic cells

    DEFF Research Database (Denmark)

    Blixt, Klas Ola; Lavrova, Olga I; Mazurov, Dmitriy V

    2012-01-01

    are Tn-