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Sample records for anticuerpos igm al

  1. IGMS Model

    EPA Pesticide Factsheets

    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.

  2. IGMS Overview

    EPA Pesticide Factsheets

    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.

  3. IGMS Construction Grants Overview

    EPA Pesticide Factsheets

    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.

  4. IGMS Search User Guide

    EPA Pesticide Factsheets

    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.

  5. Diagnóstico diferencial en la encefalitis por anticuerpos contra el receptor NMDA

    PubMed Central

    González-Valcárcel, J.; Rosenfeld, M.R.; Dalmau, J.

    2011-01-01

    Resumen Introducción La encefalitis por anticuerpos contra el receptor de NMDA (NMDAR) suele desarrollarse como un síndrome característico de evolución multifásica y diagnóstico diferencial amplio. Pacientes Presentamos a 2 pacientes diagnosticadas de encefalitis por anticuerpos NMDAR con un cuadro clínico típico, pero que inicialmente señaló otras etiologías. Discusión La afectación frecuente de pacientes jóvenes con manifestaciones psiquiátricas prominentes indica frecuentemente otras consideraciones diagnósticas; las más frecuentes son las encefalitis virales, los procesos psiquiátricos y el síndrome neuroléptico maligno. Varios síndromes previamente definidos de manera parcial o descriptiva en adultos y pacientes pediátricos probablemente eran casos de encefalitis anti-NMDAR. Conclusiones La encefalitis anti-NMDAR debe considerarse en pacientes jóvenes con manifestaciones psiquiátricas subagudas, movimientos anormales y alteraciones autonómicas. La caracterización clínica e inmunológica de esta enfermedad ha llevado a la identificación de nuevos anticuerpos que afectan a procesos de memoria, aprendizaje, conducta y psicosis. PMID:20964986

  6. Search | IGMS | Envirofacts | US EPA

    EPA Pesticide Factsheets

    2017-01-09

    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.

  7. Dust in the IGM: pro and contra

    NASA Astrophysics Data System (ADS)

    Shchekinov, Y. A.; Nath, B.

    2011-09-01

    Observations of dust grains in the intergalactic medium (IGM) allow us to study an important aspect in the evolution of galaxies. Although its existence had been previously speculated upon, direct evidence of the presence of dust in the intergalactic space has only been available recently. We discuss various issues regarding the presence of dust in the IGM—its sources, transport mechanisms from galaxies into the IGM, its effect on reddening and on cosmological studies.

  8. The validity of the radial immunodiffusion method for the quantitative determination of human IgM. Evaluation of a modified method.

    PubMed

    de Bruyn, A M; Klein, F

    1976-01-01

    Three subgroups of human IgM can be distinguished on the basis of differences of slopes of the D2 versus absolute concentration plot in the radial immunodiffusion technique (Klein et al., 1973). Individual IgM fractions, whether mono- or polyclonal, always belong to only one of these groups. The differences between the subgroups disappear after reduction of the IgM to 7S subunits. These findings provide an explanation for the large discrepancies between absolute IgM determinations in different laboratories. It follows that most of the readings of individual IgM values in the Mancini technique must be wrong by any standard, including WHO reference preparations. The insertion of a simple reduction step in the assay abolishes the differences in quantitative reactivity between IgM subgroups as well as between natural 7S and 19S IgM. This allows an absolute determination of both forms together. The values thus obtained differ considerably from the estimates given by Humphrey and Batty (1974). It also appears that the International Units of the WHO do not represent the same quantity of IgM in different reference sera. The modified method allows the determination of total monoclonal as well as polyclonal human IgM by weight.

  9. IgM in the Kidney: A Multiple Personality Disorder

    PubMed Central

    Platt, Jeffrey L.; Cascalho, Marilia

    2015-01-01

    IgM in the blood of normal individuals consists mainly of “natural” polyreactive antibodies. Natural IgM are thought to provide an initial defense against infection and 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. PMID:26323070

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

    PubMed

    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.

  11. Malignant transformation in IgM monoclonal gammopathy of undetermined significance.

    PubMed

    Montoto, S; Rozman, M; Rosiñol, L; Nadal, E; Giné, E; Aymerich, M; Ferrer, A; Esteve, J; Bosch, F; López-Guillermo, A; Bladé, J; Montserrat, E

    2003-04-01

    Monoclonal gammopathy of undetermined significance (MGUS) is a frequent disorder characterized by the presence of a small serum M-protein in individuals with no evidence of multiple myeloma (MM), Waldenstrom's macroglobulinemia (WM), or primary amyloidosis (AL). Although one fourth of these individuals will develop a malignant disease, there are no well-established predictors of outcome, particularly in the IgM type MGUS. Among 434 patients diagnosed with MGUS from 1970 to 2001 with a minimum follow-up of 1 year, 52 (27 men and 25 women; median age, 67 years) of IgM type were identified. After a median follow-up of 5 years, five patients (9.6%) have developed WM. The risk of transformation was 13.3% (95% confidence interval [CI], 0 to 27) and 27.7% (95% CI, 0.3 to 55.1) at 10 and 20 years, respectively. The variables significantly associated with transformation were the proportion of bone marrow plasma cells (BMPC) and the percentage of bone marrow lymphocytes (BML). No significant differences in the risk of transformation were found between IgM MGUS and the remaining MGUS types. Thus, in IgM MGUS the rate of transformation was similar to the risk observed in other MGUS types, the percentage of BMPC and BML being the features significantly associated with evolution into WM.

  12. The effect of reduction of IgM on the quantitative determination of IgM by radial immunodiffusion and turbidimetry.

    PubMed

    Out, T A; McDonald, J R; Woldhuis-Kant, J; Nieuwenhuys, E J

    1984-12-29

    The behaviour of different IgM proteins in radial immunodiffusion was investigated. In agreement with earlier findings differences were observed between various IgM preparations, which disappeared after reduction of IgM. The amount of IgM in several standard sera, that are used for the quantitative determination of IgM, was measured by radial immunodiffusion after reduction of IgM, and was found to be lower than hitherto accepted. It was observed that it was not necessary to perform reduction of IgM before its quantitation when a turbidimetric immunoassay was used. We conclude that (1) the standard sera that are used for the determination of IgM have to be calibrated in radial immunodiffusion after reduction of IgM and (2) the absolute amount of IgM in sera is about 0.6 times the amount that is commonly accepted.

  13. GRBs as Probes of the IGM

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  15. Successful treatment of IgM paraproteinaemic neuropathy with fludarabine

    PubMed Central

    Wilson, H.; Lunn, M.; Schey, S.; Hughes, R

    1999-01-01

    OBJECTIVES—To evaluate the response of four patients with IgM paraproteinaemic neuropathy to a novel therapy—pulsed intravenous fludarabine.
BACKGROUND—The peripheral neuropathy associated with IgM paraproteinaemia usually runs a chronic, slowly progressive course which may eventually cause severe disability. Treatment with conventional immunosuppressive regimens has been unsatisfactory. Fludarabine is a novel purine analogue which has recently been shown to be effective in low grade lymphoid malignancies.
METHODS—Four patients were treated with IgM paraproteinaemic neuropathy with intravenous pulses of fludarabine. Two of the four patients had antibodies to MAG and characteristic widely spaced myelin on nerve biopsy and a third had characteristic widely spaced myelin only. The fourth had an endoneurial lymphocytic infiltrate on nerve biopsy and a diagnosis of Waldenström's macroglobulinaemia.
RESULTS—In all cases subjective and objective clinical improvement occurred associated with a significant fall in the IgM paraprotein concentration in three cases. Neurophysiological parameters improved in the three patients examined. The treatment was well tolerated. All patients developed mild, reversible lymphopenia and 50% mild generalised myelosuppression, but there were no febrile episodes.
CONCLUSION—Fludarabine should be considered as a possible treatment for patients with IgM MGUS paraproteinaemic neuropathy.

 PMID:10209166

  16. Antibodies to myelin-associated glycoprotein (anti-Mag) in IgM amyloidosis may influence expression of neuropathy in rare patients.

    PubMed

    Garces-Sanchez, Mercedes; Dyck, Peter J; Kyle, Robert A; Zeldenrust, Steven; Wu, Yanhong; Ladha, Shafeeq S; Klein, Christopher J

    2008-04-01

    We have examined whether antibodies to myelin-associated glycoprotein (anti-MAG) influence neuropathy occurrence and phenotype in primary (AL IgM) amyloidosis. Anti-MAG and the cross-reacted sulfoglucuronyl paragloboside antibodies (SGPG) were studied in 46 patients with IgM amyloidosis (21 with polyneuropathy), and 21 matched IgM MGUS (monoclonal gammopathies of undetermined significance) controls without neuropathy. We assessed the occurrence, phenotype of neuropathy, and attributes of nerve conduction and their relation to antibody activity. Twenty of 46 patients with IgM amyloidosis (7 with and 13 without polyneuropathy) had elevation of anti-MAG or SGPG by enzyme-linked immunosorbent assay (ELISA). Two of the polyneuropathy patients with IgM amyloidosis had antibodies to MAG based on Western blot (WB) positivity. One of these patients, with the highest anti-MAG titer, had a painful sensory ataxia, with prominent demyelination, and amyloid deposition in sural nerve. The other anti-MAG WB-positive amyloid patient had an axonal neuropathy and dysautonomia. Low levels of anti-MAG antibodies were found in 12 of 21 IgM MGUS controls without neuropathy (mean follow-up, 11 years). We conclude that finding serum anti-MAG antibodies does not exclude the diagnosis of primary amyloidosis. They do not appear to affect the occurrence or expression of polyneuropathy, except possibly in occasional cases with WB positivity.

  17. A Reassessment of IgM Memory Subsets in Humans.

    PubMed

    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

    2015-10-15

    From paired blood and spleen samples from three adult donors, we performed high-throughput VH sequencing of human B cell subsets defined by IgD and CD27 expression: IgD(+)CD27(+) ("marginal zone [MZ]"), IgD(-)CD27(+) ("memory," including IgM ["IgM-only"], IgG and IgA) and IgD(-)CD27(-) cells ("double-negative," including IgM, IgG, and IgA). A total of 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 (among 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.

  18. Association of IgM monoclonal gammopathy with progressive muscular atrophy and multifocal motor neuropathy: a case-control study.

    PubMed

    Vlam, Lotte; Piepers, Sanne; Sutedja, Nadia A; Jacobs, Bart C; Tio-Gillen, Anne P; Stam, Marloes; Franssen, Hessel; Veldink, Jan H; Cats, Elisabeth A; Notermans, Nicolette C; Bloem, Andries C; Wadman, Renske I; van der Pol, W-Ludo; van den Berg, Leonard H

    2015-03-01

    Monoclonal gammopathy in patients with amyotrophic lateral sclerosis (ALS) and related disorders has been reported in small studies but the validity of the reported associations remains uncertain. Presence of monoclonal gammopathy may indicate specific pathogenic pathways and may facilitate the development of novel treatment strategies. The objective of this large case-control study was to determine the prevalence of monoclonal gammopathy in motor neuron diseases (MND) and multifocal motor neuropathy (MMN). Monoclonal gammopathy was determined by immunoelectrophoresis and immunofixation in serum from 445 patients with ALS, 158 patients with progressive muscular atrophy (PMA), 60 patients with primary lateral sclerosis (PLS), 88 patients with MMN and in 430 matched healthy controls. Anti-ganglioside antibody titers were determined in sera from patients with MMN and PMA, and in ALS and PLS patients with monoclonal gammopathy. Logistic regression analysis was used to investigate associations of monoclonal gammopathy with motor neuron diseases and clinical characteristics. Neither ALS nor PLS was associated with monoclonal gammopathy. IgM monoclonal gammopathy was more frequent in patients with PMA (8 %) (OR = 4.2; p = 0.001) and MMN (7 %) (OR = 5.8; p = 0.002) than in controls (2 %). High titers of anti-GM1 IgM antibodies were present in 43 % of MMN patients and 7 % of PMA patients. Patients with PMA and IgM monoclonal gammopathy or anti-GM1 antibodies had a higher age at onset, more often weakness of upper legs and more severe outcome than patients with MMN. PMA and MMN, but not ALS and PLS, are significantly associated with IgM monoclonal gammopathy and anti-GM1 antibodies. These results may indicate that a subset of patients presenting with PMA share pathogenic mechanisms with MMN.

  19. Impact of Natural IgM Concentration on Gene Therapy with Adenovirus Type 5 Vectors

    PubMed Central

    Qiu, Qi; Xu, Zhili; Tian, Jie; Moitra, Rituparna; Gunti, Sreenivasulu; Notkins, Abner L.

    2014-01-01

    Natural IgM inhibits gene transfer by adenovirus type 5 (Ad5) vectors. We show that polyreactive natural IgM antibodies bind to Ad5 and that inhibition of liver transduction by IgM depends on Kupffer cells. By manipulating IgM concentration in vivo, we demonstrate that IgM inhibits liver transduction in a concentration-dependent manner. We further show that differences in natural IgM between BALB/c and C57BL/6 mice contribute to lower efficiency of Ad5 gene transfer in BALB/c mice. PMID:25552715

  20. Recognition of human IgM subgroups by quantitative measurement

    PubMed Central

    Klein, F.; De Bruyn, A. M.; Radema, H.

    1973-01-01

    By means of the single radial immunodiffusion technique it is possible to detect at least two subgroups of human IgM paraproteins, if the square ring diameter is plotted against absolute concentration. These groups give different calibration lines with the same antiserum, even when no qualitative differences can be detected by the double diffusion technique. The possibility of distinguishing these groups is not limited to the use of a single antiserum. The differences between the groups are abolished by reduction of the IgM paraprotein to 7S subunits and therefore seem to be of conformational nature. No identity with other known classifications has yet been found. In one out of two cases investigated differences in quantitative reactivity were found between 19S and >19S components in the same serum. The results suggest that quantitative methods may be used to detect differences in immunoglobulin structure, when qualitative methods fail. They show that different human IgM paraproteins cannot be directly compared quantitatively by the radial immunodiffusion method. PMID:4128890

  1. Encefalitis por anticuerpos contra el receptor de NMDA: experiencia con seis pacientes pediátricos. Potencial eficacia del metotrexato

    PubMed Central

    Bravo-Oro, Antonio; Abud-Mendoza, Carlos; Quezada-Corona, Arturo; Dalmau, Josep; Campos-Guevara, Verónica

    2016-01-01

    Introducción La encefalitis por anticuerpos contra el receptor de N-metil-D-aspartato (NMDA) es una entidad cada vez más diagnosticada en edad pediátrica. A diferencia de los adultos, en muchos casos no se asocia a tumores y las manifestaciones iniciales en niños más frecuentes son crisis convulsivas y trastornos del movimiento, mientras que en los adultos predominan las alteraciones psiquiátricas. Casos clínicos Presentamos seis casos pediátricos confirmados con anticuerpos contra la subunidad NR1 del receptor de NMDA en suero y líquido cefalorraquídeo. Cinco de los casos comenzaron con crisis convulsivas como manifestación clínica inicial antes de desarrollar el cuadro clásico de esta entidad. En todos los casos se utilizaron esteroides como primera línea de tratamiento, con los que sólo se observó control de las manifestaciones en uno, por lo que el resto de los pacientes requirió inmunomoduladores de segunda línea. Todos los pacientes recibieron metotrexato como tratamiento inmunomodulador para evitar recaídas y la evolución fue a la mejoría en todos ellos. Conclusiones En nuestra serie de pacientes con encefalitis por anticuerpos contra el receptor de NMDA, ninguno se asoció a tumores. Todos los casos recibieron metotrexato por lo menos durante un año, no observamos eventos adversos clínicos ni por laboratorio, ni hubo secuelas neurológicas ni recaídas durante el tratamiento. Aunque es una serie pequeña y es deseable incrementar el número y tiempo de evolución, consideramos el metotrexato una excelente alternativa como tratamiento inmunomodulador para esta patología. PMID:24150952

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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.

  4. Low molecular weight IgM and CD5 B lymphocytes in rheumatoid arthritis.

    PubMed Central

    Xu, H; Geddes, R; Roberts-Thomson, P J

    1994-01-01

    OBJECTIVES--To evaluate the role of low molecular weight (LMW) IgM and CD5 B cells in rheumatoid arthritis (RA) and to explore the possibility that LMW IgM is derived selectively from this subset of B cells. METHODS--LMW IgM in sera and culture supernatants was detected by a sensitive immunoblot technique with an enhanced chemiluminescence detection system. CD5 B cells were determined by FACScan cytometry. In vitro studies were established in culture plates containing pokeweed mitogen with or without 2-mercaptoethanol (2-ME). Supernatants were obtained from CD5 positive hybridomas and CD5 negative hybridomas. Other immunological indices were measured by laser nephelometry. RESULTS--Circulating LMW IgM was detected in all rheumatoid patients with significantly higher levels being observed in sero-positive patients. LMW IgM correlated significantly with total IgM and RF. Peripheral blood mononuclear cells (PBMC) from the majority of the patients with RA secreted LMW IgM in vitro as did mononuclear cells from a synovial fluid sample. The addition of low concentrations of 2-ME to the culture medium enhanced the proportions of secreted monomeric IgM. In contrast, PBMC from healthy subjects secreted only trace quantities of LMW IgM. In RA no significant correlations were observed between CD5 B cells and LMW IgM and RF. LMW IgM could be detected in the supernatants from both CD5+ and CD5- B cell lines. Finally, CD5 B cells were not significantly elevated in RA and levels remained constant over time. CONCLUSION--LMW IgM exists in high concentrations in RA sera and synovial fluid. Serum level correlates with RF and IgM. In vitro studies have suggested that the occurrence of LMW IgM may be due to an intrinsic defect(s) in the assembly of the IgM pentameric molecule. LMW IgM is unlikely to be derived solely from CD5 B cells. Images PMID:7518662

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

    NASA Astrophysics Data System (ADS)

    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 0.03

  6. The contribution of naturally occurring IgM antibodies, IgM cross-reactivity and complement dependency in murine humoral responses to pneumococcal capsular polysaccharides.

    PubMed

    Jones, Hannah E; Taylor, Philip R; McGreal, Eamon; Zamze, Susanne; Wong, Simon Y C

    2009-09-25

    Immunogenicity of 12 capsular polysaccharides (CPS) from Streptococcus pneumoniae did not correlate with pre-existing levels of natural IgM anti-CPS antibodies in mice. Immunization of mice with individual CPS, with the exception of type 14 (the only neutral CPS tested), increased serum IgM that also bound other CPS serotypes independent of structural similarity or commonly known contaminants. Surprisingly only IgM response to type 4 (which has a small immunodominant epitope) was dependent on either complement C3 or complement receptors CD35/CD21. IgG anti-CPS responses were infrequently induced, but critically dependent on complement. Our results have clarified the role of complement in the induction of IgM and IgG anti-CPS antibody responses in mice and have implications for CPS vaccine development.

  7. IgM monoclonal gammopathy of undetermined significance (MGUS) and smoldering Waldenström's macroglobulinemia (SWM).

    PubMed

    Kyle, Robert A; Dispenzieri, Angela; Kumar, Shaji; Larson, Dirk; Therneau, Terry; Rajkumar, S Vincent

    2011-02-01

    Monoclonal gammopathy of undetermined significance of IgM class (IgM MGUS) was diagnosed in 213 Mayo Clinic patients who were residents of 11 counties in Southeastern Minnesota from 1960 to 1994. During long-term follow-up 29 (14%) developed non-Hodgkin lymphoma (n=17), Waldenström's macroglobulinemia (n=6), chronic lymphocytic leukemia (n=3), and AL amyloidosis (n=3) with relative risks of 15-, 262-, 6-, and 16-fold, respectively. The cumulative probability of progression to one of these disorders was 10% at 5 years, 18% at 10 years, and 24% at 15 years, approximately 1.5% per year.Forty-eight patients with SWM were identified at Mayo Clinic from 1974 to 1995. During 285 cumulative person-years of follow-up (median, 15.4 years) 34 (71%) progressed to Waldenström's macroglobulinemia (WM), 1 to AL amyloidosis, and 1 to lymphoma (total, 36 [75%]). The cumulative probability of progressing to WM, amyloidosis, or lymphoma was 6% at 1 year, 39% at 3 years, and 59% at 5 years (12% per year).

  8. Characterization of IgM in Norwegian cleaner fish (lumpfish and wrasses).

    PubMed

    Bilal, Sumaira; Lie, Kai Kristoffer; Karlsen, Odd André; Hordvik, Ivar

    2016-12-01

    The use of cleaner fish in Norwegian aquaculture has to a large extent been based on wild catches, but breeding of lumpfish and ballan wrasse is currently increasing. Due to disease problems and required vaccine development, tools to study immune responses and a better understanding of the immune system in these species is demanded. The present study comprises lumpfish (Cyclopterus lumpus) and five species of wrasses: Ballan wrasse (Labrus bergylta), rock cook (Centrolabrus exoletus), cuckoo wrasse (Labrus mixtus), corkwing wrasse (Symphodus melops), and goldsinny wrasse (Ctenolabrus rupestris). We present a comparison of the IgM sequences, phylogenetic relationship to other teleosts and characteristic features of IgM in the species studied. The lumpfish IgM heavy chain sequence was assembled from high throughput cDNA sequencing whereas the wrasse sequences were determined by molecular cloning. The secreted form of the IgM heavy chain from all species consisted of four constant Ig domains. IgM was purified from lumpfish and ballan wrasse sera by gel filtration followed by anion exchange chromatography, and polyclonal sera were produced against these proteins. Antisera against ballan wrasse IgM showed cross-reactivity to all analyzed species of wrasses, some cross-reactivity to lumpfish, very low reaction to salmon, and no reaction to cod. Anti- IgM sera against lumpfish cross-reacted to the light chain of all species studied. Wrasses and lumpfish IgM showed high binding affinities for protein A. IgM concentration in adult ballan wrasse (700-800 g) was measured by single radial immunodiffusion assay and found to be 13.4 mg/ml which is about 36% of the total protein concentration. The IgM concentration in lumpfish (600-3600 g) was estimated to 1-2.6 mg/ml, which corresponds to approximately 3% of the total protein concentration.

  9. Interaction between the IGM and a dwarf galaxy

    NASA Astrophysics Data System (ADS)

    Lora, V.; Raga, A. C.; Grebel, E. K.

    2015-04-01

    Dwarf Galaxies are the most common objects in the Universe and are believed to contain large amounts of dark matter. There are mainly three morphologic types of dwarf galaxies: dwarf ellipticals, dwarf spheroidals and dwarf irregulars. Dwarf irregular galaxies are particularly interesting in dwarf galaxy evolution, since dwarf spheroidal predecessors could have been very similar to them. Therefore, a mechanism linked to gas-loss in dwarf irregulars should be observed, i.e. ram pressure stripping. In this paper, we study the interaction between the ISM of a dwarf galaxy and a flowing IGM. We derive the weak-shock, plasmon solution corresponding to the balance between the post-bow shock pressure and the pressure of the stratified ISM (which we assume follows the fixed stratification of a gravitationally dominant dark matter halo). We compare our model with previously published numerical simulations and with the observed shape of the HI cloud around the Ho II and Pegasus dwarf irregular galaxies. We show that such a comparison provides a straightforward way for estimating the Mach number of the impinging flow.

  10. Evaluation of rubella virus immunoglobulin G (IgG) and IgM assays with the new Vidia instrument.

    PubMed

    Medici, Maria Cristina; Martinelli, Monica; Albonetti, Valeria; Chezzi, Carlo; Dettori, Giuseppe

    2008-05-01

    For rubella virus immunoglobulin G (IgG) and IgM detection, Vidia assays were compared to Vidas, AxSYM, and Liaison assays with 419 serum samples. Only Vidia produced a sensitivity of 100% for IgG and IgM. Vidia specificities were 98.4% for IgG and 99.8% for IgM, versus Vidas specificities of 100 and 99.3%. Vidia IgG and IgM assays performed equally well.

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

    PubMed Central

    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

  12. Ly-1 B cells: functionally distinct lymphocytes that secrete IgM autoantibodies.

    PubMed Central

    Hayakawa, K; Hardy, R R; Honda, M; Herzenberg, L A; Steinberg, A D; Herzenberg, L A

    1984-01-01

    Studies presented here introduce another perspective on the mechanisms responsible for IgM autoantibody production. A unique subpopulation of B lymphocytes (Ly-1 B) that concomitantly expresses IgM, IgD, Ia, and Ly-1 membrane glycoproteins is present at higher frequencies in NZB and NZB-related mice. The Ly-1 B subpopulation in these autoimmune animals is responsible for the "spontaneous" IgM secretion demonstrated with cultured NZB spleen cells and contains the cells that secrete typical NZB IgM autoantibodies to single-stranded DNA and to thymocytes. In addition, the Ly-1 B population in normal mouse strains (and in NZB) contains virtually all of the spleen cells that secrete IgM autoantibodies reactive with bromelain-treated mouse erythrocytes. Since a different B-cell subpopulation (IgM+, IgD-, Ly-1) secretes most of the IgM antibodies produced in responses to exogenous antigens, we conclude that Ly-1 B cells constitute a functionally distinct B-cell population important in certain kinds of autoimmunity. PMID:6609363

  13. Transcriptional Heterogeneity of IgM+ Cells in Rainbow Trout (Oncorhynchus mykiss) Tissues

    PubMed Central

    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. PMID:24324826

  14. Genetics Home Reference: X-linked hyper IgM syndrome

    MedlinePlus

    ... prognosis of a genetic condition? Genetic and Rare Diseases Information Center Frequency X-linked hyper IgM syndrome is estimated to occur in 2 per million newborn boys. Related Information What information about a genetic condition can ...

  15. Physiological IgM Class Catalytic Antibodies Selective for Transthyretin Amyloid*

    PubMed Central

    Planque, Stephanie A.; Nishiyama, Yasuhiro; Hara, Mariko; Sonoda, Sari; Murphy, Sarah K.; Watanabe, Kenji; Mitsuda, Yukie; Brown, Eric L.; Massey, Richard J.; Primmer, Stanley R.; O'Nuallain, Brian; Paul, Sudhir

    2014-01-01

    Peptide bond-hydrolyzing catalytic antibodies (catabodies) could degrade toxic proteins, but acquired immunity principles have not provided evidence for beneficial catabodies. Transthyretin (TTR) forms misfolded β-sheet aggregates responsible for age-associated amyloidosis. We describe nucleophilic catabodies from healthy humans without amyloidosis that degraded misfolded TTR (misTTR) without reactivity to the physiological tetrameric TTR (phyTTR). IgM class B cell receptors specifically recognized the electrophilic analog of misTTR but not phyTTR. IgM but not IgG class antibodies hydrolyzed the particulate and soluble misTTR species. No misTTR-IgM binding was detected. The IgMs accounted for essentially all of the misTTR hydrolytic activity of unfractionated human serum. The IgMs did not degrade non-amyloidogenic, non-superantigenic proteins. Individual monoclonal IgMs (mIgMs) expressed variable misTTR hydrolytic rates and differing oligoreactivity directed to amyloid β peptide and microbial superantigen proteins. A subset of the mIgMs was monoreactive for misTTR. Excess misTTR was dissolved by a hydrolytic mIgM. The studies reveal a novel antibody property, the innate ability of IgMs to selectively degrade and dissolve toxic misTTR species as a first line immune function. PMID:24648510

  16. Spectrotypic analysis of IgM and IgA rheumatoid factors.

    PubMed Central

    Chu, J L; Gharavi, A E; Elkon, K B

    1986-01-01

    The spectrotypes of IgA and IgM rheumatoid factors (RF) were analysed in whole serum as well as immunoglobulin fractions and purified RF from patients with one of three autoimmune disorders. As predicted from the pI ranges of normal human serum IgM and IgA in agarose, IgM RF had near neutral pIs, whereas IgA RF showed more acidic (lower) pI values. Serum IgA and IgM RF from patients with rheumatoid arthritis or the sicca syndrome showed considerable charge heterogeneity whereas IgM RF from mixed cryoglobulinaemia or rheumatoid vasculitis patients showed monoclonal and oligoclonal banding patterns respectively. Clonotypic analysis was best achieved with isolated light and heavy chains from highly purified RF. The IgA RF spectrotypes from unmodified paired serum and saliva IgA were clearly different whereas after desialation, similar pI values and, in one case, similar spectrotypes were observed. These observations are compatible with the hypothesis that serum and saliva IgA RF are derived from similar clonal precursors. The methods used in these studies may also be of use in the analysis of IgA and IgM antibody diversity in a number of other situations. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:3708903

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

    PubMed

    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.

  18. The role of IgM rheumatoid factor in experimental immune vasculitis.

    PubMed Central

    Floyd, M; Tesar, J T

    1979-01-01

    The effect of IgM rhematoid factor (RF) on reversepassive cutaneous Arthus reaction in rats was studied. The RF was obtained from the serum cryoglobulin of a patient with symptoms of purpura, arthralgia and digital gangrene. The cryoglobulins was of IgG-IgM type and when given i.v it induced a prompt hypocomplementaemia in experimental animals. The purified RF also induced low serum complement levels when injected i.v. along with complexes of non-complement-fixing, aggregated IgG. A reverse passive Arthus reaction was induced by intradermal injection of IgG anti-bovine serum albumin (BSA), followed by an i.v. dose of antigen (Ag). The cutaneous inflammatory reaction was aggravated by simultaneous administration of IgM RF intradermally, but not by IgM without antibody (Ab) properties. Intradermal injection of low concentrations of non-complement-fixing IgG anti-BSA, along with normal human IgM, followed by i.v. injection of BSA, resulted in a complete lack of cutaneous inflammation. At higher Ab concentrations there was only a mild inflammation. However, when IgM RF was substituted for normal IgM and injected with non-complement-fixing anti-BSA, an effective reverse passive cutaneous Arthus reaction and vasculitis was induced. The inflammatory response was greatly suppressed by decomplementation of animals by cobra venom factor. This study provides evidence favouring an inflammatory, complement-dependent role for RF in vasculitis. PMID:157238

  19. Platelet antibodies of the IgM class in immune thrombocytopenic purpura

    SciTech Connect

    Cines, D.B.; Wilson, S.B.; Tomaski, A.; Schreiber, A.D.

    1985-04-01

    The clinical course and response to therapy of patients with immune thrombocytopenic purpura (ITP) are not completely determined by the level of IgG present on the platelet surface. It is possible that antibodies of other immunoglobulin classes also play a role in platelet destruction in some of these patients. Therefore, the authors studied 175 patients with ITP for the presence of IgM anti-platelet antibodies using radiolabeled polyclonal or monoclonal anti-IgM. They observed that 57% of patients with clinical ITP had increased levels of IgM on their platelets, compared with normal controls and patients with thrombocytopenia who did not have ITP. They obtained similar results using either radiolabeled polyclonal or monoclonal anti-IgM, reagents whose integrity was first characterized using erythrocytes coated with defined amounts of IgM antibody. Among patients with increased platelet-IgM there was a significant correlation both with the presence of increased platelet-C3 as well as the amount of platelet-C3. The authors demonstrated the presence of warm-reacting IgM anti-platelet antibodies in the plasma of two of these patients who were further studied. These studies demonstrate the presence of warm-reacting IgM anti-platelet antibodies in some patients with ITP. They suggest that the binding of complement to platelets by IgM antibodies may initiate platelet clearance as well as enhance the effect of IgG antibodies in ITP.

  20. A natural human IgM that binds to gangliosides is therapeutic in murine models of amyotrophic lateral sclerosis

    PubMed Central

    Xu, Xiaohua; Denic, Aleksandar; Jordan, Luke R.; Wittenberg, Nathan J.; Warrington, Arthur E.; Wootla, Bharath; Papke, Louisa M.; Zoecklein, Laurie J.; Yoo, Daehan; Shaver, Jonah; Oh, Sang-Hyun; Pease, Larry R.; Rodriguez, Moses

    2015-01-01

    ABSTRACT 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. PMID:26035393

  1. Treatment failure related to intrathecal immunoglobulin M (IgM) synthesis, cerebrospinal fluid IgM, and interleukin-10 in patients with hemolymphatic-stage sleeping sickness.

    PubMed

    Lejon, Veerle; Robays, Jo; N'Siesi, François Xavier; Mumba, Dieudonné; Hoogstoel, Annemie; Bisser, Sylvie; Reiber, Hansotto; Boelaert, Marleen; Büscher, Philippe

    2007-06-01

    Human African trypanosomiasis treatment is stage dependent, but the tests used for staging are controversial. Central nervous system involvement and its relationship with suramin treatment failure were assessed in 60 patients with parasitologically confirmed hemolymphatic-stage Trypanosoma brucei gambiense infection (white blood cell count of IgM; as determined by nephelometry and the point-of-care LATEX/IgM test), total protein, and trypanosome-specific antibody was assessed. The IgM and interleukin-10 levels in serum were measured; and the presence of neurological signs, intrathecal IgM synthesis, and blood-CSF barrier dysfunction was determined. After suramin treatment, 14 of 60 patients had relapses (23%). Relapses were significantly correlated with intrathecal IgM synthesis (odds ratio [OR], 46; 95% confidence interval [CI], 8 to 260), a CSF IgM concentration of >or=1.9 mg/liter (OR, 11.7; 95% CI, 2.7 to 50), a CSF end titer by the LATEX/IgM assay of >or=2 (OR, 10.4; 95% CI, 2.5 to 44), and a CSF interleukin-10 concentration of >10 pg/ml (OR, 5; 95% CI, 1.3 to 20). The sensitivities of these markers for treatment failure ranged from 43 to 79%, and the specificities ranged from 74 to 93%. The results show that T. brucei gambiense-infected patients who have signs of neuroinflammation in CSF and who are treated with drugs recommended for use at the hemolymphatic stage are at risk of treatment failure. This highlights the need for the development and the evaluation of accurate point-of-care tests for the staging of human African trypanosomiasis.

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

    NASA Astrophysics Data System (ADS)

    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.

  3. A monoclonal IgM protein with antibody-like activity for human albumin.

    PubMed

    Hauptman, S; Tomasi, T B

    1974-03-01

    The serum of a patient (L'ec) with an IgM lambda monoclonal protein was noted to bind albumin on immunoelectrophoresis. Analytical ultracentrifugation of the L'ec serum demonstrated 23S and 12S peaks, but no 4S (albumin) boundary. Immunologically identical 20S and 9S IgM proteins were isolated from the serum and the addition in vitro of either the patient's albumin or albumin isolated from normal serum was shown to reconstitute the 23S and 12S boundaries. The binding of high molecular weight IgM to albumin was demonstated by Sephadex G200 chromatography with (125)I-labeled albumin and isolated IgM. Immunoelectrophoresis of the L'ec IgM developed with aggregated albumin (reverse immunoelectrophoresis) also demonstrated the binding of albumin to IgM. That all of the patient's IgM complexed with albumin was shown by affinity chromatography employing an aggregated albumin-immunoadsorbent column. Binding was shown to be of the noncovalent type by polyacrylamide gel electrophoresis in 8 M urea. With hot trypsin proteolysis, Fabmu and Fcmu5 fragments were isolated, and monomer albumin was shown to complex only with the Fabmu fragment by both analytical ultracentrifugation and molecular sieve chromatogaphy employing (125)I-labeled Fab fragments. 1 mol of Fabmu fragment bound 1 mol of monomer albumin. Polymers of human albumin, produced by heat aggregation, precipitated with the isolated L'ec protein on gel diffusion analysis and, when coated on sheep red blood cells, gave a hemagglutination titer greater than 1 million with the whole L'ec serum. 50 additional monoclonal IgM, 33 IgA, and 80 IgG sera failed to show precipitation or hemagglutination with aggregated albumin. Native monomer albumin inhibited precipitation only at high concentrations (> 50 mg/ml); dimer albumin or fragments of albumin produced by trypsin digestion inhibited at low concentrations (0.4 mg/ml). No reactivity occurred with the albumin of five other mammalian species, including bovine. The L

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

    PubMed Central

    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

  5. Treponema pallidum specific IgM haemagglutination test for serodiagnosis of syphilis.

    PubMed Central

    Sato, T; Kubo, E; Yokota, M; Kayashima, T; Tomizawa, T

    1984-01-01

    The Treponema pallidum specific IgM haemagglutination (TP-IgM-HA) test uses erythrocytes sensitised with antiserum to human IgM to separate IgM from IgG in serum. Specific antitreponemal IgM captured in this way is detected by adding a second reagent comprising erythrocytes sensitised with T pallidum antigen. Eighty two serum samples from 82 patients with untreated syphilis, 521 samples from 73 patients with treated syphilis, and 1872 samples from people who did not have syphilis were examined by the 19S(IgM)-TPHA (T pallidum haemagglutination), IgM-FTA-ABS (fluorescent treponemal antibody absorbed), TP-IgM-ELISA (enzyme linked immunosorbent assay), and TP-IgM-HA tests for the presence of 19S(IgM) antibodies specific to treponemes. The sensitivity of the TP-IgM-HA test was 97.6% and the specificity was 99.7%. We also traced IgM specific to treponemes in untreated patients with primary syphilis by four different tests. The TP-IgM-HA test results clearly reflected the effect of the treatment. PMID:6394097

  6. Case Report: Acute Cerebellar Thrombosis in an Adult Patient with IgM Nephropathy

    PubMed Central

    Adike, Abimbola; Cherry, Mariyam; Awar, Melina

    2015-01-01

    IgM nephropathy is a relatively rare cause of idiopathic nephrotic syndrome.1 It was initially described by van de Putte,2 then by Cohen and Bhasin in 1978, as a distinctive feature of mesangial proliferative glomerulonephritis.2 It is typically characterized by diffuse IgM deposits on the glomeruli and diffuse mesangial hypercellularity. Little is known about the pathogenesis and treatment of this disease.1,3 We describe a patient who presented with nonspecific symptoms of epigastric pain, nausea, and early satiety. Abdominal imaging and endoscopies were unremarkable. She was found to have significant proteinuria (6.4 g/24 hours), hyperlipidemia, and edema consistent with a diagnosis of nephrotic syndrome. Kidney biopsy was performed and confirmed an IgM nephropathy. Less than 2 weeks after her diagnosis of IgM nephropathy, she presented with an acute cerebellar stroke. Thrombophilia is a well-known complication of nephrotic syndrome, but a review of the literature failed to show an association between IgM nephropathy and acute central nervous system thrombosis. PMID:27057296

  7. Diagnostic and prognostic significance of the IgM antibody to the Hepatitis delta virus

    SciTech Connect

    Farci, P.; Gerin, J.L.; Aragona, M.; Lindsey, I.; Crivelli, O.; Balestrieri, A.; Smedile, A.; Thomas, H.C.; Rizzetto, M.

    1986-03-21

    The IgM class antibody to the hepatitis delta virus (HDV) was determined in different clinical categories of hepatitis B surface antigen carriers infected by the HDV (positive in the test for total antibody to HDV). The IgM antibody was found at high titers in each 70 patients with inflammatory liver disease and at a low titer in one six patients with inactive cirrhosis; it was not found in eight carriers with normal liver histology. Testing for Igm antibody to HDV distinguishes hepatitis B surface antigen carriers who have underlying inflammatory HDV liver disease from those with past HDV infection and provides prognostic information on the course of chronic HDV hepatitis.

  8. Cold urticaria associated with C4 deficiency and elevated IgM.

    PubMed

    Stafford, C T; Jamieson, D M

    1986-04-01

    Various immunologic abnormalities have been implicated in cold urticaria. This is the first report of cold urticaria associated with C4 deficiency and elevated IgM. A 12-year-old male developed urticaria upon exposure to cold. He denied fever, purpura, hemoglobinuria, Raynaud's disease, or arthralgias. Family history was negative for cold urticaria. Immunologic studies revealed elevated IgM (186 mg/dL) as well as decreased CH100 and C4 (8.0 mg/dL). C1, C2, and C3 were normal. Ice cube skin test was positive, but passive transfer tests were negative. Biopsy was not diagnostic for vasculitis, although it revealed a few immunofluorescent deposits of IgM and C4. Complement genetic studies revealed deficiency of two half-null C4 haplotypes expressed as C4A*3QO and B*2QO.

  9. Detection of MYD88 L265P and WHIM-like CXCR4 mutation in patients with IgM monoclonal gammopathy related disease.

    PubMed

    Cao, Xin-Xin; Meng, Qi; Cai, Hao; He, Tian-Hua; Zhang, Cong-Li; Su, Wei; Sun, Jian; Li, Yue; Xu, Wei; Zhou, Dao-Bin; Li, Jian

    2017-03-09

    A broad spectrum of diseases are associated with IgM monoclonal gammopathy, including Waldenstrom macroglobulinemia (WM), various types of B cell non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), primary amyloidosis (AL), and monoclonal gammopathy of undetermined significance (MGUS); these are called IgM monoclonal gammopathy related diseases (IgM-RD). We investigated MYD88 L265P and WHIM-like CXCR4 mutations in various IgM-RD. Patients with serum immunofixation electrophoresis confirmed IgM monoclonal gammopathy who had enough material for DNA extraction and presented between January 2008 and October 2016 at Peking Union Medical College Hospital were enrolled in this cohort. We performed real-time allele-specific-polymerase chain reaction and Sanger sequencing to explore the presence of MYD88 L265P and WHIM-like CXCR4 mutations. One hundred and twelve patients (64 male and 48 female patients) were included in this retrospective study. The median age at diagnosis was 62 years (range, 30-84 years). In total, 64 patients (57.1%) carried the MYD88 L265P mutation and 14 patients (12.5%) carried the CXCR4 WHIM-like mutation. We identified the MYD88 L265P somatic variant in cases with WM (39/42), MGUS (8/18), NHL (14/41, including 4/13 diffuse large B cell lymphoma (DLBCL), 1/8 mucosa-associated lymphoid tissue, 3/6 splenic marginal zone lymphoma (SMZL), 1/4 chronic lymphocytic leukemia, 2/3 nodal marginal zone lymphoma (NMZL), 1/2 mantle cell lymphoma, 1 Burkitt lymphoma, and 1 B cell NHL that could not be classified), primary AL (2/2), and IgM-PN (1/1). The mutation was absent in five patients with Cryoglobulinemia, two with primary cold agglutinin disease and one with MM. The CXCR4 WHIM-like mutation was present in 10/42 patients with WM, 3/41 with NHL (1 DLBCL, 1 SMZL, and 1 NMZL), and 1/18 patients with IgM MGUS. Among the patients with NHL, those with the mutated MYD88 L265P genotype were younger and had lower level of IgG and IgA than the patients with the

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

    PubMed

    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 < 0.05) with 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.

  11. IgM+ Memory B Cell Expression Predicts HIV-Associated Cryptococcosis Status

    PubMed Central

    Subramaniam, Krishanthi; Metzger, Brian; Hanau, Lawrence H.; Guh, Alice; Rucker, Lisa; Badri, Sheila; Pirofski, Liise-anne

    2009-01-01

    Background The role of B cells in resistance to Cryptococcus neoformans disease (i.e., cryptococcosis) is unknown. Given evidence that IgM+ memory B cells are required for immunity to other encapsulated pathogens, we hypothesized that these cells might contribute to resistance to cryptococcosis. Methods We compared levels of IgM expression on memory B cells in 29 HIV-infected individuals who had a history of cryptococcosis (the HIV+CN+ group) with levels in 30 human immunodeficiency virus (HIV)–infected subjects who had no history of cryptococcosis (the HIV+CN− group) and 20 HIV-uninfected subjects who had no history of cryptococcosis (the HIV− group) (cohort 1). We also determined levels of IgM expression on memory B cells in banked samples obtained before cryptococcosis onset from 31 participants in the Multicenter AIDS Cohort Study, of whom 8 had HIV infection and subsequently developed cryptococcosis (the HIV+CN+ group), 8 had HIV infection and did not develop cryptococcosis (the HIV+CN− group), and 15 did not have HIV infection and did not develop cryptococcosis (the HIV− group) (cohort 2). Results In cohort 1, the percentage of memory B cells that expressed IgM was lower among HIV+CN+ subjects, compared with HIV+CN− subjects (P < .01) and HIV− subjects (P <.05); expression of IgM on ≤50% of memory B cells was a significant predictor of C. neoformans disease status (odds ratio, 5.5; P = .03). In cohort 2, the percentage of memory B cells that expressed IgM was lower in HIV+CN+ subjects than in HIV+CN− subjects (P = .02) and HIV− subjects (P < .01); an IgM+ memory B cell percentage of ≤38.5% was a significant predictor of future development of cryptococcosis (odds ratio, 14; P = .02). Conclusions These findings suggest that HIV-infected persons in whom the percentage of memory B cells that express IgM is decreased might be at greater risk for the development of cryptococcosis. PMID:19527168

  12. Granular IgM Deposition at Basement Membrane Zone in an Infant with Diffuse Cutaneous Mastocytosis

    PubMed Central

    Kumudhini, Subramanian; Rao, Raghavendra; Salgaonkar, Gauri; Shetty, Sricharith; Pai, Sathish

    2016-01-01

    Diffuse Cutaneous mastocytosis (DCM) occurs due to abnormal accumulation of mast cells in the skin. We report an 8-month-old infant presented papulovesicular lesions, predominantly on the trunk. Skin biopsy revealed subepidermal bulla, interspersed with mast cells, eosinophils and neutrophils. Direct immunofluorescence microscopy of perilesional skin revealed nonspecific deposition of IgM in granular pattern along the dermoepidermal junction. PMID:27688466

  13. Mechanisms underlying acquired von Willebrand syndrome associated with an IgM paraprotein.

    PubMed

    Mayerhofer, M; Haushofer, A; Kyrle, P A; Chott, A; Müllner, C; Quehenberger, P; Worel, N; Traby, L; Eichinger, S

    2009-09-01

    Acquired von Willebrand (vW) syndrome is a rare bleeding disorder which is frequently associated with immunological, malignant or cardiovascular disorders. The underlying pathomechanisms, particularly in patients with IgM monoclonal gammopathies, often remain unknown. We report a patient with indolent small B-cell lymphoma (immunocytoma) and plasmacytic differentiation with an IgM kappa paraprotein who was admitted with retroperitoneal haematoma. Medical history and coagulation testing were consistent with acquired vW syndrome. vW immunohistochemistry showed normal cytoplasmic labelling of endothelial cells and megakaryocytes, whereas the lymphomatous infiltrate was negative. Acquired vW syndrome due to adsorption of vW factor on malignant cells was thus excluded. In the multimeric analysis, all multimers were present similar to that in type 1 vW syndrome, but the triplet structures were blurred. The bands on serum immunofixation electrophoresis were also atypically broadened, which suggested complex formation between the IgM and vW factor. Immunoprecipitation studies showed that the 176-kDa proteolytic fragment of vW factor co-precipitated with the IgM paraprotein in the patient but not in the controls, suggesting a specific interaction between vW factor and the paraprotein in the patient. The patient required surgery and was successfully managed by chemotherapy consisting of rituximab and fludarabin as well as plasma exchange.

  14. IgM binding to sialosyllactosaminylparagloboside in a patient with polyradiculoneuropathy due to Mycoplasma pneumoniae infection.

    PubMed

    Inuzuka, T; Miyatani, N; Baba, H; Tanaka, M; Tanaka, K; Sato, S; Nakamura, K; Miyatake, T

    1988-07-01

    IgM in serum without paraprotein in a patient with polyradiculoneuropathy due to a Mycoplasma pneumoniae infection reacted specifically with a ganglioside, sialosyllactosaminylparagroboside (SLPG), in a human peripheral nerve on a thin-layer chromatogram plate by an immunostaining technique. This finding suggests the possibility that anti-SLPG antibody in the patient's serum may play a role in the pathogenesis of neuropathy.

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

    PubMed

    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.

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

    PubMed

    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.

  17. Baryonic Content in the Warm-Hot IGM at Low Redshift

    NASA Technical Reports Server (NTRS)

    Sonneborn, George; Shull, M.; Danforth, C.; Moos, W.

    2007-01-01

    Baryons are 4.5% of the universe's mass/energy density; only 10% of these are in stars, galaxies, and clusters. At low-redshift 90% of baryons are in the IGM, 30% in Ly-alpha forest, but most are in hot gas (10(exp 5-7) K) produced by shocks during structure formation. O VI 1032-38 A are the best tracers of this gas. The distribution of O VI absorbers observed by FUSE rises as N(sup -2+/-0.2, down to 10(exp 13)/sq cm. Integrated to logN=13, 7% of baryons reside in the O VI-bearing IGM at 10% solar metallicity, T approx. 10(exp 5.5) K. At redshift z<0.1 metals have been transported less than 800/h kpc from L* galaxies and 200/h kpc from 0.1 L* galaxies. The steepness of dN/dz means that low-N absorbers contribute an equal mass of hot IGM as higher N gas. The total mass of O VI-bearing gas in the IGM depends on determining the turnover in dN/dz at low N(O VI). Future observations by FUSE are needed to reach lower N and to reduce the uncertainty in the dN/dz power law.

  18. Acute postoperative inflammatory polyarthritis associated with a lone IgM cardiolipin antibody

    PubMed Central

    Chua, Ignatius; Jawad, Ali

    2015-01-01

    While the most recognised complication after joint surgery is septic arthritis, other forms of joint pathology may occur. We present a case of postoperative polyarthritis with high inflammatory markers, which responded to a course of prednisolone. The occurrence of high IgM cardiolipin antibodies that normalised with treatment suggests that this condition is a form of transient autoimmunity. PMID:25733090

  19. Sensitivity and specificity of mu-capture ELISA for detection of enterovirus IgM.

    PubMed

    Bendig, J W; Molyneaux, P

    1996-05-01

    The sensitivity and specificity of an in-house mu-capture enzyme linked immunosorbent assay (ELISA) for enterovirus IgM in routine use was determined by analysing the results of 77 serum samples from 55 enterovirus culture-positive patients with aseptic meningitis and single serum samples from 140 patients with other infections. In addition, sera from 10 laboratory staff pre- and post-polio virus vaccination and 20 rheumatoid factor positive sera were tested for specificity. On testing the first serum specimen received, only 21 of 55 patients (38%) with aseptic meningitis yielded a positive result, rising to 33 of 55 (60%) on testing a second sample, where available. Out of 14 patients from whom multiple serum samples were tested and negative results obtained with the first serum, 12 were positive with the second sample (86%). Only patients with acute hepatitis A produced a significant number of false positives by the enterovirus ELISA (12 out of 20), but the reverse was not true: patients with enterovirus IgM did not produce false positive results in tests for hepatitis A IgM. Excluding samples positive for hepatitis A IgM, the number of non-enterovirus infections correctly reported as negative was 118 out of 120--a specificity of 98%. This test is probably the most useful serological test available at present for diagnosing recent enterovirus infection, although the limited sensitivity needs to be borne in mind.

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

    PubMed

    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.

  1. Lymphocyte surface IgD and IgM in Macaca monkeys: ontogeny, tissue distribution and occurrence on individual lymphocytes.

    PubMed Central

    Martin, L N; Leslie, G A

    1977-01-01

    A proportion of lymphocytes in blood, spleen and lymph nodes of nonhuman primates had immunoglobulin on their surfaces detectable by fluorescent antibody to human IgM and IgD. The majority of the individual lymphocytes having either IgM or IgD on their surfaces possessed both classes of immunoglobulin. Lymphocyte surface IgD was capped independently of surface IgM on the same cell when incubated at 37 degrees with anti-IgD. Lymphocytes with surface IgM and/or IgD were present in blood at birth and the percentages over the first 6 months of life were increased compared to older monkeys. A corona of cells faintly positive for both IgM and IgD was observed around germinal centres of both lymph nodes and spleen. Images Figure 1 Figure 2 PMID:412779

  2. Membrane-controlled depletion of complement activity by spin-label-specific IgM

    PubMed Central

    Humphries, Gillian M. K.; McConnell, Harden M.

    1977-01-01

    Complement depletion mediated by high molecular weight (IgM) rabbit antibodies specifically bound to spin-label lipid haptens dispersed in model membranes is controlled by various physical attributes of those membranes other than the total number of exposed determinants that they provide. Carrier lipids used at 32° were (i) a “fluid” phosphatidylcholine (PC), (ii) a “solid” PC, and (iii) a cholesterol/PC mixture. The concentration of hapten in the plane of the membranes (two-dimensional concentration) was varied while the overall hapten molarity (three-dimensional concentration) was kept constant. Both specific binding and the efficiency of depletion by IgM are markedly enhanced by systematically decreasing the average distance between haptens (∞ → 26 A). Heterogeneous distribution was found to be more favorable than a random homogeneous distribution of the same number of haptens in the same total quantity of lipids. IgM efficiency is also markedly increased by the inclusion of cholesterol in PC membranes, an effect thought to result from enhanced projection of the determinant from the surface of the membrane and hence increased accessibility to the antibody-binding site. Furthermore, the efficiency of IgM was increased by using haptens dispersed in fluid rather than in solid PC membranes. The results are consistent with the hypothesis that IgM molecules must be bound to a critical multiple of antigenic determinants at a membrane surface in order to induce complement-mediated attack and that subtle variation of the physical state of membrane antigens can be the crucial factor in determining the outcome of this type of efferent immune response. PMID:198789

  3. 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

    PubMed Central

    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

  4. 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.

    PubMed

    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.

  5. Glycan-independent binding and internalization of human IgM to FCMR, its cognate cellular receptor

    NASA Astrophysics Data System (ADS)

    Lloyd, Katy A.; Wang, Jiabin; Urban, Britta C.; Czajkowsky, Daniel M.; Pleass, Richard J.

    2017-02-01

    IgM is the first antibody to be produced in immune responses and plays an important role in the neutralization of bacteria and viruses. Human IgM is heavily glycosylated, featuring five N-linked glycan sites on the μ chain and one on the J-chain. Glycosylation of IgG is known to modulate the effector functions of Fcγ receptors. In contrast, little is known about the effect of glycosylation on IgM binding to the human Fcμ receptor (hFCMR). In this study, we identify the Cμ4 domain of IgM as the target of hFCMR, and show that binding and internalization of IgM by hFCMR is glycan-independent. We generated a homology-based structure for hFCMR and used molecular dynamic simulations to show how this interaction with IgM may occur. Finally, we reveal an inhibitory function for IgM in the proliferation of T cells.

  6. Glycan-independent binding and internalization of human IgM to FCMR, its cognate cellular receptor

    PubMed Central

    Lloyd, Katy A.; Wang, Jiabin; Urban, Britta C.; Czajkowsky, Daniel M.; Pleass, Richard J.

    2017-01-01

    IgM is the first antibody to be produced in immune responses and plays an important role in the neutralization of bacteria and viruses. Human IgM is heavily glycosylated, featuring five N-linked glycan sites on the μ chain and one on the J-chain. Glycosylation of IgG is known to modulate the effector functions of Fcγ receptors. In contrast, little is known about the effect of glycosylation on IgM binding to the human Fcμ receptor (hFCMR). In this study, we identify the Cμ4 domain of IgM as the target of hFCMR, and show that binding and internalization of IgM by hFCMR is glycan-independent. We generated a homology-based structure for hFCMR and used molecular dynamic simulations to show how this interaction with IgM may occur. Finally, we reveal an inhibitory function for IgM in the proliferation of T cells. PMID:28230186

  7. Characterisation of echidna IgM provides insights into the time of divergence of extant mammals.

    PubMed

    Belov, Katherine; Hellman, Lars; Cooper, Desmond W

    2002-11-01

    The immunobiology of monotremes is poorly understood. In this paper, we describe the characterisation of the heavy chain of IgM from Tachyglossus aculeatus, the short-beaked echidna. The echidna heavy chain constant region of IgM (Cmu)was isolated from a spleen cDNA library using a Trichosurus vulpecula probe. It has approximately 46.5% amino acid identity to marsupial and eutherian Cmus, and approximately 30% amino acid identity with Cmu from birds and reptiles. Phylogenetic analysis of mammalian Cmu provides strong support for the Theria hypothesis, with a sister grouping of the eutherians and marsupials to the exclusion of the monotremes. Cmu sequences suggest that monotremes and therians separated approximately 170 million years ago (mya), marsupials and eutherians separated approximately 130mya, and Australian and American marsupials separated approximately 65mya.

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

    SciTech Connect

    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.

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

    SciTech Connect

    Gnedin, Nickolay Y.; Becker, George D.; Fan, Xiaohui

    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.

  10. Inadequacy of IgM antibody tests for diagnosis of Rocky Mountain Spotted Fever.

    PubMed

    McQuiston, Jennifer H; Wiedeman, Caleb; Singleton, Joseph; Carpenter, L Rand; McElroy, Kristina; Mosites, Emily; Chung, Ida; Kato, Cecilia; Morris, Kevin; Moncayo, Abelardo C; Porter, Susan; Dunn, John

    2014-10-01

    Among 13 suspected Rocky Mountain spotted fever (RMSF) cases identified through an enhanced surveillance program in Tennessee, antibodies to Rickettsia rickettsii were detected in 10 (77%) patients using a standard indirect immunofluorescent antibody (IFA) assay. Immunoglobulin M (IgM) antibodies were observed for 6 of 13 patients (46%) without a corresponding development of IgG, and for 3 of 10 patients (30%) at least 1 year post-onset. However, recent infection with a spotted fever group rickettsiae could not be confirmed for any patient, based on a lack of rising antibody titers in properly timed acute and convalescent serologic specimens, and negative findings by polymerase chain reaction testing. Case definitions used in national surveillance programs lack specificity and may capture cases that do not represent current rickettsial infections. Use of IgM antibodies should be reconsidered as a basis for diagnosis and public health reporting of RMSF and other spotted fever group rickettsiae in the United States.

  11. Prevalence, specificity and functionality of anti-ganglioside antibodies in neuropathy associated with IgM monoclonal gammopathy.

    PubMed

    Stork, Abraham C J; Jacobs, Bart C; Tio-Gillen, Anne P; Eurelings, Marijke; Jansen, Marc D; van den Berg, Leonard H; Notermans, Nicolette C; van der Pol, W-Ludo

    2014-03-15

    IgM antibodies against gangliosides and their complexes were studied in sera from 54 patients with polyneuropathy and IgM monoclonal gammopathy (IgM-PNP) without anti-MAG antibodies. Anti-ganglioside antibodies were found in 19 (35%) patients. Five (9%) patients had antibodies against ganglioside complexes. IgM antibodies against gangliosides activated complement in vitro. Light chain usage was restricted to kappa or lambda in most, but not all patients. In conclusion, anti-ganglioside antibodies in IgM-PNP are common, display pathogenic properties and do not always arise from a monoclonal B cell proliferation.

  12. Biclonal IgD and IgM Plasma Cell Myeloma: A Report of Two Cases and a Literature Review.

    PubMed

    Chen, Zhongchuan W; Kotsikogianni, Ioanna; Raval, Jay S; Roth, Christine G; Rollins-Raval, Marian A

    2013-01-01

    Biclonal plasma cell myelomas producing two different isotypes of immunoglobulins are extremely rare entities; to date, the combination of IgD and IgM secretion by a biclonal plasma cell myeloma has not been reported. Bone marrow biopsy immunohistochemical studies in two cases revealed neoplastic plasma cells coexpressing IgD and IgM, but serum protein electrophoresis identified only the IgM monoclonal paraprotein in both cases. Biclonal plasma cell myelomas, while currently not well characterized in terms of their clinical behavior, should be distinguished from B-cell lymphoma with plasmacytic differentiation, given the different therapeutic implications. Both cases reported herein demonstrated chemotherapy-resistant clinical courses.

  13. Three-dimensional structure of the Fab from a human IgM cold agglutinin.

    PubMed

    Cauerhff, A; Braden, B C; Carvalho, J G; Aparicio, R; Polikarpov, I; Leoni, J; Goldbaum, F A

    2000-12-01

    Cold agglutinins (CAs) are IgM autoantibodies characterized by their ability to agglutinate in vitro RBC at low temperatures. These autoantibodies cause hemolytic anemia in patients with CA disease. Many diverse Ags are recognized by CAs, most frequently those belonging to the I/i system. These are oligosaccharides composed of repeated units of N:-acetyllactosamine, expressed on RBC. The three-dimensional structure of the Fab of KAU, a human monoclonal IgM CA with anti-I activity, was determined. The KAU combining site shows an extended cavity and a neighboring pocket. Residues from the hypervariable loops V(H)CDR3, V(L)CDR1, and V(L)CDR3 form the cavity, whereas the small pocket is defined essentially by residues from the hypervariable loops V(H)CDR1 and V(H)CDR2. This fact could explain the V(H)4-34 germline gene restriction among CA. The KAU combining site topography is consistent with one that binds a polysaccharide. The combining site overall dimensions are 15 A wide and 24 A long. Conservation of key binding site residues among anti-I/i CAs indicates that this is a common feature of this family of autoantibodies. We also describe the first high resolution structure of the human IgM C(H)1:C(L) domain. The structural analysis shows that the C(H)1-C(L) interface is mainly conserved during the isotype switch process from IgM to IgG1.

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

    PubMed

    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.

  15. Integrated Gravity Mapping System (IGMS) Study Program for Aircraft and Land Vehicles. Volume 1.

    DTIC Science & Technology

    1982-03-01

    Office (SP24) for the US Navy, under the management of Sperry Systems Management. 1.3 Scope 1.3.1 General The Integrated Gravity Mapping System (IGMS...program plan outlined on Figure 2-1 incorporates the experiences gained on the GSS ADM system for Sperry /SSPC/USN, which was delivered and installed...5 5 * . .SS * use of a smaller militarized computer. Improvement observed as a result of efforts conducted under the Sperry /SSPO program will be

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

    PubMed

    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.

  17. A High-Resolution Study of the IGM at 5 < z < 6.4

    NASA Astrophysics Data System (ADS)

    Becker, G. D.; Sargent, W. L. W.; Rauch, M.; Simcoe, R. A.

    2005-12-01

    The complete Lyman-alpha absorption seen in the spectra of z > 6 quasars suggest that the reionization of the IGM may have completed as late as z = 6.2. However, this late reionization scenario remains controversial due in part to studies of galaxy luminosity functions, which favor a highly-ionized IGM out to z > 6.5. In order to improve our understanding of the IGM at these redshifts, we have acquired Keck/HIRES spectra of nine quasars at 4.8 < z < 6.4. These are the first high-resolution spectra ever taken at z > 4.6, and are providing the first detailed look at the very high-redshift IGM. We will present the first results from this data set, highlighting the evolution of the Lyman-alpha forest and the quasar proximity regions. The high-resolution data also reveal an overabundance of O I systems at z > 6 towards SDSS J1148+5251. These O I absorbers may represent the last pockets of neutral gas to be reionized at z ˜ 6. Alternatively, they may be caused by enriched galaxy halos physically similar to those observed at lower redshift. For these systems we are able to measure accurate column densities of O I, C II, and Si II. The relative abundances are consistent with the yields of ordinary Type II supernovae, with at most ˜ 30% of the silicon contributed by very massive stars. GDB and WLWS have been supported by the NSF through grants AST 99-00733 and AST 02-06067. MR has been supported by the NSF under grant AST 00-98492. RAS has been supported by the MIT Pappalardo Fellowship program.

  18. Hyper IgM syndrome presenting as chronic suppurative lung disease.

    PubMed

    Montella, Silvia; Maglione, Marco; Giardino, Giuliana; Di Giorgio, Angela; Palamaro, Loredana; Mirra, Virginia; Ursini, Matilde Valeria; Salerno, Mariacarolina; Pignata, Claudio; Caffarelli, Carlo; Santamaria, Francesca

    2012-09-19

    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.

  19. Hyper IgM syndrome presenting as chronic suppurative lung disease

    PubMed Central

    2012-01-01

    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. PMID:22992442

  20. A patterned recombinant human IgM guides neurite outgrowth of CNS neurons

    NASA Astrophysics Data System (ADS)

    Xu, Xiaohua; Wittenberg, Nathan J.; Jordan, Luke R.; Kumar, Shailabh; Watzlawik, Jens O.; Warrington, Arthur E.; Oh, Sang-Hyun; Rodriguez, Moses

    2013-07-01

    Matrix molecules convey biochemical and physical guiding signals to neurons in the central nervous system (CNS) and shape the trajectory of neuronal fibers that constitute neural networks. We have developed recombinant human IgMs that bind to epitopes on neural cells, with the aim of treating neurological diseases. Here we test the hypothesis that recombinant human IgMs (rHIgM) can guide neurite outgrowth of CNS neurons. Microcontact printing was employed to pattern rHIgM12 and rHIgM22, antibodies that were bioengineered to have variable regions capable of binding to neurons or oligodendrocytes, respectively. rHIgM12 promoted neuronal attachment and guided outgrowth of neurites from hippocampal neurons. Processes from spinal neurons followed grid patterns of rHIgM12 and formed a physical network. Comparison between rHIgM12 and rHIgM22 suggested the biochemistry that facilitates anchoring the neuronal surfaces is a prerequisite for the function of IgM, and spatial properties cooperate in guiding the assembly of neuronal networks.

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

    PubMed Central

    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

  2. Transgenic mouse model of IgM(+) lymphoproliferative disease mimicking Waldenström macroglobulinemia.

    PubMed

    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

    2016-11-04

    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-L(d)-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.

  3. Nomenclature of Toso, Fas apoptosis inhibitory molecule 3, and IgM FcR.

    PubMed

    Kubagawa, Hiromi; Carroll, Michael C; Jacob, Chaim O; Lang, Karl S; Lee, Kyeong-Hee; Mak, Tak; McAndrews, Monica; Morse, Herbert C; Nolan, Garry P; Ohno, Hiroshi; Richter, Günther H; Seal, Ruth; Wang, Ji-Yang; Wiestner, Adrian; Coligan, John E

    2015-05-01

    Hiromi Kubagawa and John E. Coligan coordinated an online meeting to define an appropriate nomenclature for the cell surface glycoprotein presently designated by different names: Toso, Fas apoptosis inhibitory molecule 3 (FAIM3), and IgM FcR (FcμR). FAIM3 and Faim3 are the currently approved symbols for the human and mouse genes, respectively, in the National Center for Biotechnology Information, Ensembl, and other databases. However, recent functional results reported by several groups of investigators strongly support a recommendation for renaming FAIM3/Faim3 as FCMR/Fcmr, a name better reflecting its physiological function as the FcR for IgM. Participants included 12 investigators involved in studying Toso/FAIM3(Faim3)/FμR, representatives from the Human Genome Nomenclature Committee (Ruth Seal) and the Mouse Genome Nomenclature Committee (Monica McAndrews), and an observer from the IgM research field (Michael Carroll). In this article, we provide a brief background of the key research on the Toso/FAIM3(Faim3)/FcμR proteins, focusing on the ligand specificity and functional activity, followed by a brief summary of discussion about adopting a single name for this molecule and its gene and a resulting recommendation for genome nomenclature committees.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27698861

  5. Evaluation of a rapid IgM detection test for diagnosis of acute leptospirosis in dogs.

    PubMed

    Lizer, J; Grahlmann, M; Hapke, H; Velineni, S; Lin, D; Kohn, B

    2017-02-24

    Recently, a lateral flow assay (LFA) for detection of Leptospira-specific IgM in canine sera became commercially available in Europe. The present study aims to evaluate the diagnostic performance of this assay using canine sera from a collection of diagnostic accessions. Diagnostic sensitivity was assessed by testing 37 acute-phase and 9 corresponding convalescent-phase sera from dogs with a confirmed diagnosis of leptospirosis. Specificity was determined by testing sera from sick dogs with non-leptospiral infections (n=15) and healthy dogs with incomplete history of vaccination (n=45). During acute phase of illness, LFA scored positive for 28/37 sera with a sensitivity of 75.7 per cent while only 9/37 (24.3 per cent) samples were positive on microscopic agglutination test. The specificity of the LFA was 98.3 per cent (59/60). This test showed 89.7 and 100 per cent overall agreements with clinical diagnosis for acute-phase and convalescent-phase sera, respectively. The impact of vaccination on the LFA was also determined and vaccine-stimulated IgM responses were negative in 19/25 (76 per cent) dogs at 12 weeks post vaccination. In conclusion, the LFA is a rapid and reliable test for early detection of Leptospira-specific IgM during acute phase of canine leptospirosis. However, interpretation of a positive result must be made in the context of clinical signs and vaccination history.

  6. Laboratory diagnosis of rheumatoid arthritis: a solid phase radioassay for IgG and IgM antiglobulins.

    PubMed Central

    Nineham, L J; Hay, F C; Roitt, I M

    1976-01-01

    A technique suitable for the routine estimation of IgM and IgG antiglobulins has been devised. The assay involves the binding of antiglobulins to plastic tubes coated with rabbit immunoglobulin: the amount of antiglobulin bound is then determined by adding radiolabelled antihuman IgG or IgM. The conditions for the assay have been examined and optimal incubation times and amounts of reagents established. Verification of the antibody nature of antiglobulin activity has been obtained. Both IgG and IgM antiglobulins were raised in virtually all seropositive rheumatoid arthritics, and most seronegative patients gave elevated values for either IgM or IgG rheumatoid factors. The use of an anti-light chain reagent as a screening test for total antiglobulins was investigated. These tests should prove valuable in diagnosis and permit quantitative evaluation of research studies. PMID:1087638

  7. Role of Natural Autoantibodies and Natural IgM Anti-Leucocyte Autoantibodies in Health and Disease

    PubMed Central

    Lobo, Peter Isaac

    2016-01-01

    We review how polyreactive natural IgM autoantibodies (IgM-NAA) protect the host from invading micro-organisms and host neo-antigens that are constantly being produced by oxidation mechanisms and cell apoptosis. Second, we discuss how IgM-NAA and IgM anti-leukocyte antibodies (IgM-ALA) inhibits autoimmune inflammation by anti-idiotypic mechanisms, enhancing removal of apoptotic cells, masking neo-antigens, and regulating the function of dendritic cells (DC) and effector cells. Third, we review how natural IgM prevents autoimmune disorders arising from pathogenic IgG autoantibodies, triggered by genetic mechanisms (e.g., SLE) or micro-organisms, as well as by autoreactive B and T cells that have escaped tolerance mechanisms. Studies in IgM knockout mice have clearly demonstrated that regulatory B and T cells require IgM to effectively regulate inflammation mediated by innate, adaptive, and autoimmune mechanisms. It is, therefore, not surprising why the host positively selects such autoreactive B1 cells that generate IgM-NAA, which are also evolutionarily conserved. Fourth, we show that IgM-ALA levels and their repertoire can vary in normal humans and disease states and this variation may partly explain the observed differences in the inflammatory response after infection, ischemic injury, or after a transplant. We also show how protective IgM-NAA can be rendered pathogenic under non-physiological conditions. We also review IgG-NAA that are more abundant than IgM-NAA in plasma. However, we need to understand if the (Fab)2 region of IgG-NAA has physiological relevance in non-disease states, as in plasma, their functional activity is blocked by IgM-NAA having anti-idiotypic activity. Some IgG-NAA are produced by B2 cells that have escaped tolerance mechanisms and we show how such pathogenic IgG-NAA are regulated to prevent autoimmune disease. The Fc region of IgG-NAA can influence inflammation and B cell function in vivo by binding to activating and inhibitory Fc

  8. Sequence similarities among kappa IIIb chains of monoclonal human IgM kappa autoantibodies

    PubMed Central

    1984-01-01

    Light chains of the serologically and chemically defined V region sub- subgroup kappa IIIb are preferentially associated with several types of human IgM kappa (monoclonal) autoantibodies and are remarkably homologous in primary structure, as evidenced by partial amino acid sequence data. To establish the extent of homology among such proteins, we have determined the complete variable region (V) sequence of the light chains of four monoclonal IgM kappa autoantibodies, of which two (GAR and GOT) are rheumatoid factors (RFs), the third (SON) has anti- apo beta lipoprotein specificity, and the fourth (PIE) binds specifically to intermediate filaments. The region encoded by the V kappa segment gene (positions 1-95) in all four light (L) chains is virtually identical in sequence, differing by only one residue in the FR3 of protein SON and in the first CDR of protein GOT. Further, the CDR3 of kappa chain SON contains an additional residue (prolyl) located at the carboxyl-terminus of the V segment. The region encoded by the J gene (positions 96-108) is identical after position 96 for the two RFs GAR and GOT (J kappa 2), but different in proteins SON (J kappa 4) and PIE (J kappa 1). The amino acid residue at position 96, located in CDR3 at the site of combinatoriaL joining of the V kappa and J kappa gene segments and involved as a contacting residue in the hapten binding site, is different in all four light chains. These results demonstrate the extensive homology in sequence among light chains of IgM kappa autoantibodies and indicate that a particular V kappa germ line gene, kappa IIIb, is expressed as a phylogenetic response to certain self antigens or as part of a selection process by which these autoimmune responses are regulated. PMID:6432934

  9. How to Search for Islands of Neutral Hydrogen in the z ~ 5.5 IGM

    NASA Astrophysics Data System (ADS)

    Malloy, Matthew; Lidz, Adam

    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 < xH \\scriptsize{I}> ≳ 0.05 and the deuterium feature observable with additional high-resolution spectra for < xH \\scriptsize{I}> ≳ 0.2.

  10. Murine Visceral Leishmaniasis: IgM and Polyclonal B-Cell Activation Lead to Disease Exacerbation

    PubMed Central

    Deak, Eszter; Jayakumar, Asha; Wing Cho, Ka; Goldsmith-Pestana, Karen; Dondji, Blaise; Lambris, John D.; McMahon-Pratt, Diane

    2010-01-01

    In visceral leishmaniasis, the draining lymph node (DLN) is the initial site for colonization and establishment of infection after intradermal transmission by the sand fly vector; however, little is known about the developing immune response within this site. Using an intradermal infection model, which allows for parasite visceralization, we have examined the ongoing immune responses in the DLN of BALB/c mice infected with L. infantum. Although not unexpected, at early times post-infection there is a marked B cell expansion in the DLN, which persists throughout infection. However, the characteristics of this response were of interest; as early as day 7 post-infection, polyclonal antibodies (TNP, OVA, chromatin) were observed and the levels appeared comparable to the specific anti-leishmania response. Although B-cell-deficient JHD BALB/c mice are relatively resistant to infection, neither B-cell-derived IL-10 nor B-cell antigen presentation appear to be primarily responsible for the elevated parasitemia. However, passive transfer and reconstitution of JHD BALB/c with secretory immunoglobulins, (IgM or IgG; specific or non-specific immune complexes) results in increased susceptibility to L. infantum infection. Further, JHD BALB/c mice transgenetically reconstituted to secrete IgM demonstrated exacerbated disease in comparison to wild type BALB/c mice as early as 2 days post-infection. Evidence suggests that complement activation (generation of C5a) and signaling via the C5aR (CD88) is related to the disease exacerbation caused by IgM rather than cytokine levels (IL-10 or IFN-γ). Overall these studies indicate that polyclonal B cell activation, which is known to be associated with human visceral leishmaniasis, is an early and intrinsic characteristic of disease and may represent a target for therapeutic intervention. PMID:20213734

  11. Production and characterization of monoclonal antibodies to IgM of Pacific herring (Clupea pallasii)

    USGS Publications Warehouse

    Purcell, Maureen K.; Bromage, Erin S.; Silva, Jessica; Hansen, John D.; Badil, Samantha M.; Woodson, James C.; Hershberger, Paul K.

    2012-01-01

    Pacific herring (Clupea pallasii) have a central role in the North Pacific ecosystem as a forage fish species and are natural reservoirs of several important finfish pathogens, including Viral hemorrhagic septicemia virus (VHSV). Here, we report the identification of the gene encoding the immunoglobulin mu (IgM) heavy chain, as well as the development and characterization of monoclonal antibodies (MAbs) that specifically react with Pacific herring IgM. Pacific herring immunoglobulin was purified and consisted of heavy and light chains of approximately 80 and 25 kDa. Three hybridoma clones were initially identified by ELISA as reactive with purified immunoglobulin but only one clone was able to detect an 80 kDa protein in Pacific and Atlantic herring (Clupea harengus) whole plasma by denaturing western blot. However, all three MAbs were able to precipitate an 80 kDa protein from Pacific herring and LCMS sequencing of peptide fragments derived from this protein matched the predicted amino acid sequence of the cloned, heavy chain gene. In addition, two of the MAbs stained cells within the putative lymphocyte gates for the spleen, anterior kidney and posterior kidney but were not reactive for myeloid/granulocyte gates, which is consistent with these MAbs reacting with surface IgM+ B-cells. To our knowledge, this is the first report of IgM-related gene sequences and anti-IgM monoclonal antibodies from any member of the family Clupeidae. The antibodies produced in this study are critical for achieving our long-term goal of conducting serological surveillance to assess pathogen exposure in natural populations of Pacific herring.

  12. Early Detection of NSCLC with scFv Selected against IgM Autoantibody

    PubMed Central

    Pedchenko, Tetyana; Mernaugh, Ray; Parekh, Dipti; Li, Ming; Massion, Pierre P.

    2013-01-01

    Survival of patients with lung cancer could be significantly prolonged should the disease be diagnosed early. Growing evidence indicates that the immune response in the form of autoantibodies to developing cancer is present before clinical presentation. We used a phage-displayed antibody library to select for recombinant scFvs that specifically bind to lung cancer-associated IgM autoantibodies. We selected for scFv recombinant antibodies reactive with circulating IgM autoantibodies found in the serum of patients with early stage lung adenocarcinoma but not matched controls. Discriminatory performance of 6 selected scFvs was validated in an independent set of serum from stage 1 adenocarcinoma and matching control groups using two independent novel methods developed for this application. The panel of 6 selected scFvs predicted cancer based on seroreactivity value with sensitivity of 0.8 and specificity of 0.87. Receiver Operative Characteristic curve (ROC) for combined 6 scFv has an AUC of 0.88 (95%CI, 0.76–1.0) as determined by fluorometric microvolume assay technology (FMAT) The ROC curve generated using a homogeneous bridging Mesa Scale Discovery (MSD) assay had an AUC of 0.72 (95% CI, 0.59–0.85). The panel of all 6 antibodies demonstrated better discriminative power than any single scFv alone. The scFv panel also demonstrated the association between a high score - based on seroreactivity - with poor survival. Selected scFvs were able to recognize lung cancer associated IgM autoantibodies in patient serum as early as 21 months before the clinical presentation of disease. The panel of antibodies discovered represents a potential unique non-invasive molecular tool to detect an immune response specific to lung adenocarcinoma at an early stage of disease. PMID:23585862

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

    SciTech Connect

    Malloy, Matthew; Lidz, Adam

    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.

  14. Human African trypanosomiasis: a latex agglutination field test for quantifying IgM in cerebrospinal fluid.

    PubMed Central

    Lejon, V.; Büscher, P.; Sema, N. H.; Magnus, E.; Van Meirvenne, N.

    1998-01-01

    LATEX/IgM, a rapid agglutination test for the semi-quantitative detection of IgM in cerebrospinal fluid of patients with African trypanosomiasis, is described in this article. The lyophilized reagent has been designed for field use and remains stable at 45 degrees C for one year. The test has been evaluated on cerebrospinal fluid samples from trypanosome-infected and non-infected patients, by comparison with commercial latex agglutination, radial immunodiffusion, and nephelometry. All test systems yielded similar results. PMID:10191550

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

    PubMed

    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.

  16. Intrathecal somatic hypermutation of IgM in multiple sclerosis and neuroinflammation.

    PubMed

    Beltrán, Eduardo; Obermeier, Birgit; Moser, Markus; Coret, Francisco; Simó-Castelló, María; Boscá, Isabel; Pérez-Miralles, Francisco; Villar, Luisa M; Senel, Makbule; Tumani, Hayrettin; Hohlfeld, Reinhard; Casanova, Bonaventura; Dornmair, Klaus

    2014-10-01

    Intrathecal oligoclonal bands of the cerebrospinal fluid are considered the most important immunological biomarkers of multiple sclerosis. They typically consist of clonally expanded IgG antibodies that underwent affinity maturation during sustained stimulation by largely unknown antigens. In addition, ∼40% of patients with multiple sclerosis have oligoclonal bands that consist of expanded IgM antibodies. We investigated the molecular composition of IgM- and IgG-chains from cerebrospinal fluid of 12 patients with multiple sclerosis, seven patients with other neurological diseases, and eight healthy control subjects by high-throughput deep-sequencing and single-cell PCR. Further, we studied the expression of activation-induced cytidine deaminase, the key enzyme for affinity maturation of antibodies, in cerebrospinal fluid samples of 16 patients. From the cerebrospinal fluid of two multiple sclerosis patients we isolated single B cells and investigated the co-expression of antibody chains with activation-induced cytidine deaminase. In striking contrast to IgM-chains from peripheral blood, IgM-chains from cerebrospinal fluid of patients with multiple sclerosis or neuroborreliosis showed a high degree of somatic hypermutation. We found a high content of mutations that caused amino acid exchanges as compared to silent mutations. In addition, more mutations were found in the complementarity determining regions of the IgM-chains, which interact with yet unknown antigens, as compared to framework regions. Both observations provide evidence for antigen-driven affinity maturation. Furthermore, single B cells from the cerebrospinal fluid of patients with multiple sclerosis co-expressed somatically hypermutated IgM-chains and activation-induced cytidine deaminase, an enzyme that is crucial for somatic hypermutation and class switch recombination of antibodies and is normally expressed during activation of B cells in germinal centres. Clonal tracking of particular IgM(+) B

  17. Competition between Serum IgG, IgM, and IgA Anti-Glycan Antibodies

    PubMed Central

    Muthana, Saddam M.; Xia, Li; Campbell, Christopher T.; Zhang, Yalong; Gildersleeve, Jeffrey C.

    2015-01-01

    Anti-glycan antibodies are an abundant subpopulation of serum antibodies with critical functions in many immune processes. Changes in the levels of these antibodies can occur with the onset of disease, exposure to pathogens, or vaccination. As a result, there has been significant interest in exploiting anti-glycan antibodies as biomarkers for many diseases. Serum contains a mixture of anti-glycan antibodies that can recognize the same antigen, and competition for binding can potentially influence the detection of antibody subpopulations that are more relevant to disease processes. The most abundant antibody isotypes in serum are IgG, IgM, and IgA, but little is known regarding how these different isotypes compete for the same glycan antigen. In this study, we developed a multiplexed glycan microarray assay and applied it to evaluate how different isotypes of anti-glycan antibodies (IgA, IgG, and IgM) compete for printed glycan antigens. While IgG and IgA antibodies typically outcompete IgM for peptide or protein antigens, we found that IgM outcompete IgG and IgA for many glycan antigens. To illustrate the importance of this effect, we provide evidence that IgM competition can account for the unexpected observation that IgG of certain antigen specificities appear to be preferentially transported from mothers to fetuses. We demonstrate that IgM in maternal sera compete with IgG resulting in lower than expected IgG signals. Since cord blood contains very low levels of IgM, competition only affects maternal IgG signals, making it appear as though certain IgG antibodies are higher in cord blood than matched maternal blood. Taken together, the results highlight the importance of competition for studies involving anti-glycan antibodies. PMID:25807519

  18. Rituximab impairs immunoglobulin (Ig)M and IgG (subclass) responses after influenza vaccination in rheumatoid arthritis patients

    PubMed Central

    Westra, J; van Assen, S; Wilting, K R; Land, J; Horst, G; de Haan, A; Bijl, M

    2014-01-01

    Rituximab (RTX) treatment in rheumatoid arthritis (RA) patients severely hampers humoral response after influenza vaccination as determined by haemagglutination inhibition assay (HI). It is not known whether HI reflects both immunoglobulin (Ig)M and IgG (subclass) influenza response, and whether IgM antibodies contribute to the low rate of influenza infection seen in RA patients. Twenty RA patients on methotrexate (MTX), 23 on RTX and 28 healthy controls (HC) received trivalent influenza subunit vaccination. Before and 28 days after vaccination, H1N1- and H3N2-specific antibodies were measured by HI and by IgM and IgG (subclass) enzyme-linked immunosorbent assay (ELISA). B cell activating factor (BAFF) levels were determined in serum samples before vaccination. Vaccination induced a significant increase of IgM and IgG (IgG1 and IgG3) antibodies against both strains in the HC and MTX groups (all P < 0·01), but not in the RTX group. HI correlated significantly in all cases with IgG (IgG1) but not with IgM. In RTX late patients (RTX treatment 6–10 months before vaccination), IgG (IgG1 and IgG3) response to vaccination was restored, but not IgM response. BAFF levels were significantly increased in RA-RTX patients and correlated with total IgG levels. Haemagglutination inhibition assay, used as gold standard, detects primarily IgG (IgG1) responses. IgM- and IgG influenza-specific antibodies increase after vaccination in HC and RA patients except in patients on RTX treatment. BAFF levels are increased in both early and late RTX-treated patients, but do not correlate with an influenza-specific antibody response. PMID:24889761

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

    PubMed

    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.

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

    SciTech Connect

    Hashimoto, Yosuke; Shimizu, Taro; Mima, Yu; Abu Lila, Amr S.; Ishida, Tatsuhiro; Kiwada, Hiroshi

    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

  1. Diffuse cutaneous bullous mastocytosis with IgM deposits at dermo-epidermal junction.

    PubMed

    Slavescu, Kinga Cristina; Chiorean, Roxana; Danescu, Sorina; Bota, Madalina; Rogojan, Liliana; Baican, Adrian

    2016-03-01

    Cutaneous mastocytosis is a disease characterized by the infiltration and proliferation of mast cells in the skin. In children, the most common form of presentation is urticaria pigmentosa, while the diffuse cutaneous bullous mastocytosis is one of the rarest subtypes seen. The aim of this paper is to present a case of diffuse bullous mastocytosis with detection of IgM deposits at dermo-epidermal junction using direct immunofluorescence (DIF) microscopy. The diagnosis of diffuse bullous mastocytosis is a challenge, and DIF microscopy is necessary in order to exclude an autoimmune bullous disorder. However, IgM deposits at dermo-epidermal junction can be nonspecific, being found in a variety of skin disorders. A 6-month-old girl presented with bullous lesions and erosions on the scalp and the trunk. During hospitalization, further bullous lesions appeared, along with generalized erythrodermia. Skin biopsy revealed aspects of urticaria pigmentosa. Taking into account the clinical findings, the case was enclosed as bullous mastocytosis. Treatment included the avoidance of trigger factors, and administration of antihistamines along with a short-term course of systemic steroids. The evolution was favorable, with remission of the existing lesions and without occurrence of new ones.

  2. Hepatitis induced by an IgM monoclonal antibody against procarboxypeptidase R.

    PubMed

    He, Lianying; Asai, Suzuka; Kawamura, Takeshi; Kimbara, Noriaki; Tada, Toyohiro; Okada, Hidechika; Okada, Noriko

    2005-01-01

    Procarboxypeptidase R (proCPR), also known as thrombin-activatable fibrinolysis inhibitor (TAFI), is present in plasma and can be activated to carboxypeptidase R (CPR) by trypsin-like enzymes such as thrombin and plasmin. CPR has the carboxypeptidase B-like activity that can inactivate the inflammatory peptides such as C5a by removing the C-terminal arginine and can interfere with fibrinolysis by removing C-terminal lysine residue of fibrin. In the present study, we conducted to produce monoclonal antibodies (mAbs) by using spleen cells from proCPR-deficient mice immunized by partially purified mouse proCPR. The mAbs obtained were IgM isotype and reacted with proCPR and interfered with activation of proCPR to CPR by thrombin-thrombomodulin complex. Some BALB/c mice implanted with the hybridoma died in 7 days, and intravenous injection of the mAb to BALB/c mice induced transient elevation of GOT and GPT in plasma although injection to the deficient mice did not. Furthermore, the histological features showed the focally lesions in liver tissue of BALB/c mice injected with the mAb. Since liver is the major site of proCPR synthesis, IgM mAb to proCPR should have induced local inflammation at the side resulting in induction of hepatitis.

  3. Differential IgM expression distinguishes two types of pediatric Burkitt lymphoma in mouse and human

    PubMed Central

    Eason, Anthony B.; Sin, Sang-Hoon; Lin, Carolina; Damania, Blossom; Park, Steven; Fedoriw, Yuri; Bacchi, Carlos E.; Dittmer, Dirk P.

    2016-01-01

    Endemic Burkitt lymphoma (eBL) is primarily a childhood cancer in parts of Africa and Brazil. Classic studies describe eBL as a homogeneous entity based on t(8;14) IgH-Myc translocation and clinical response to cytotoxic therapy. By contrast, sporadic BL (sBL) in Western countries is considered more heterogeneous, and affects both children and adults. It is overrepresented in AIDS patients. Unlike diffuse large B cell lymphoma (DLBCL), molecular subtypes within BL have not been well defined. We find that differential IgM positivity can be used to describe two subtypes of pediatric Burkitt lymphoma both in a high incidence region (Brazil), as well as in a sporadic region (US), suggesting the phenotype is not necessarily geographically isolated. Moreover, we find that IgM positivity also distinguishes between early and late onset BL in the standard Eμ-Myc mouse model of BL. This suggests that the t(8;14) translocation not only can take place before, but also after isotype switch recombination, and that IgM-negative, t(8;14) positive lymphomas in children should nevertheless be considered BL. PMID:27566574

  4. Lansoprazole increases serum IgG and IgM in H. pylori-infected patients.

    PubMed

    Matsukawa, Y; Kurosaka, H; Kato, K; Hayashi, I; Minekawa, K; Arakawa, Y; Sawada, S

    2007-01-01

    Proton-pump inhibitors have been reported to influence the human immune system, we therefore evaluated the effect of lansoprazole, a proton-pump inhibitor, on humoral immunity. Patients with gastric ulcer received lansoprazole 30 mg/day for 8 weeks, and serum immunoglobulins were evaluated before and upon completion of the treatment. There were 79 patients with gastric ulcer; 51 were H. pylori-infected and 28 were H. pylori-uninfected. Eighteen patients positive for H. pylori were receiving at least one non-steroidal anti-inflammatory drug, and 12 patients negative for H. pylori received one non-steroidal anti-inflammatory drug. H. pylori-infected patients showed significant increases in serum immunoglobulins G and M 8 weeks after the start of lansoprazole treatment (P<0.001 for IgG and P<0.01 for IgM), but uninfected patients did not. Even when H. pylori-infected patients receiving a non-steroidal anti-inflammatory drug or low-dose aspirin were analyzed separately, these increases were seen (P<0.001 for IgG and P<0.005 for IgM). Lansoprazole elevated serum levels of immunoglobulins G and M in gastric ulcer patients with H. pylori infection, particularly in those receiving non-steroidal anti-inflammatory drugs. Deducing from these observations, lansoprazole might alter the Th1 shift in the immune response induced by H. pylori infection.

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

    PubMed

    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.

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

    PubMed

    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.

  7. The Insertion Green Monster (iGM) Method for Expression of Multiple Exogenous Genes in Yeast

    PubMed Central

    Labunskyy, Vyacheslav M.; Suzuki, Yo; Hanly, Timothy J.; Murao, Ayako; Roth, Frederick P.; Gladyshev, Vadim N.

    2014-01-01

    Being a simple eukaryotic organism, Saccharomyces cerevisiae provides numerous advantages for expression and functional characterization of proteins from higher eukaryotes, including humans. However, studies of complex exogenous pathways using yeast as a host have been hampered by the lack of tools to engineer strains expressing a large number of genetic components. In addition to inserting multiple genes, it is often desirable to knock out or replace multiple endogenous genes that might interfere with the processes studied. Here, we describe the “insertion Green Monster” (iGM) set of expression vectors that enable precise insertion of many heterologous genes into the yeast genome in a rapid and reproducible manner and permit simultaneous replacement of selected yeast genes. As a proof of principle, we have used the iGM method to replace components of the yeast pathway for methionine sulfoxide reduction with genes encoding the human selenoprotein biosynthesis machinery and generated a single yeast strain carrying 11 exogenous components of the selenoprotein biosynthetic pathway in precisely engineered loci. PMID:24776987

  8. Quantification of plasma cells in labial salivary glands: increased expression of IgM in Sjögren's syndrome.

    PubMed

    Speight, P M; Cruchley, A; Williams, D M

    1990-03-01

    Plasma cells expressing IgG, IgA and IgM were quantified in labial salivary glands from patients with Sjögren's syndrome (SS) and compared with glands showing non-specific inflammatory changes and normal controls. In all glands the predominant isotype was IgA but in SS there was a significant increase in both the number and proportions of IgG and IgM positive cells (P less than 0.002). In particular, all SS cases contained greater than 10% IgM positive cells (mean = 26.8 +/- 15.5). The results suggest that accumulation of IgM positive plasma cells may be a specific finding in SS and support the concept that the glandular lesions may be a site of B-cell clonal expansion. Since most B-cell hyperproliferative states in SS, including lymphoma, are associated with synthesis of IgM simple quantification of plasma cells may have important diagnostic and prognostic significance.

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

    PubMed

    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.

  10. IgG, IgM, and IgA antinuclear antibodies in discoid and systemic lupus erythematosus patients.

    PubMed

    Jost, Sheridan A; Tseng, Lin-Chiang; Matthews, Loderick A; Vasquez, Rebecca; Zhang, Song; Yancey, Kim B; Chong, Benjamin F

    2014-01-01

    IgG antinuclear antibodies (ANAs) are elevated in patients with systemic lupus erythematosus (SLE) compared with patients with discoid lupus erythematosus (DLE). To provide an expanded immunologic view of circulating ANAs in lupus patients, we compared the expressions of IgG, IgM, and IgA ANAs in DLE and SLE patients. In this cross-sectional study, sera from age-, gender-, and ethnic-matched SLE (N = 35), DLE (N = 23), and normal patients (N = 22) were tested for IgG, IgM, and IgA ANAs using enzyme-linked immunosorbent assays (ELISAs) and indirect immunofluorescence (IIF) with monkey esophagus as substrate. ELISAs showed elevated levels of IgG ANA, IgM ANA, and IgG/IgM ANA ratios in SLE patients compared with DLE and normal patients. IgA ANA expression was higher in SLE and DLE patients versus normal patients. IIF studies showed higher percentages of patients positive for IgG, IgM, and IgA ANAs in the SLE group. Higher IgG/IgM ANA ratios in SLE than DLE show enhanced class-switching and a more sustained humoral response in SLE. They also suggest a potential connection of IgM ANAs with disease containment.

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

    PubMed

    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.

  12. 2D immunoblots show differential response of mouse IgG and IgM antibodies to antigens of mammary carcinoma 4 T1 cells

    PubMed Central

    2014-01-01

    Background Immunosuppression in breast cancer has been reported in women and in the highly metastatic mouse mammary tumor model 4 T1. The immunosuppressive environment complicates the use of the humoral response against the tumor as an immunodiagnostic tool. IgM has not been used in immunodiagnostic in part because its antitumor responses, both innate and adaptive, have not been studied in function of time in breast cancer. We show a new approach to analyzing the mouse humoral immune response, and compare the evolution with time of IgG and IgM responses against the antigens of 4 T1 cells. Methods The study is based on 2-dimensional immunoblotting detection of antigens from 4 T1 cells by the IgG and IgM antibodies in the serum of female mice injected with 4 T1 cells. Results There was a high variability in the intra-and inter-mouse response. Variability in the IgM response was manifested as a pattern of spots that could become a multibinomial variable of 0 and 1, which could represent a signature of the immune response. Different numbers of spots was found in the IgG and IgM responses from week 1 to 5. On average, the IgM had more but the IgG response decrease with the time. The natural IgM at t = 0 responds stronger than w1; the adaptive response of both IgM and IgG were elicited where, with the former being stronger better than the latter. Antigens that are recognized by some female mice in the first week are also recognized by other female mice at time 0. Contamination of the natural IgM makes difficult use the adaptive IgM as a tool for immunodiagnostic. Conclusions IgM and IgG response varied with the time and individuals. Spot variation in 2D pattern for the natural IgM could be expressed as a binomial signature, which opens up the way to correlate a particular pattern with resistance or susceptibility. This uncovers a battery of IgMs for each individual to confront cancer or infections. The possibility to differentiate between adaptive IgM antibodies

  13. Specific recognition pattern of IgM and IgG antibodies produced in the course of experimental paracoccidioidomycosis.

    PubMed Central

    Vaz, C A; Mackenzie, D W; Hearn, V M; Camargo, Z P; Singer-Vermes, L M; Burger, E; Calich, V L

    1992-01-01

    Specific IgM and IgG responses to Paracoccidioides brasiliensis produced in resistant and susceptible mice during experimental paracoccidioidomycosis were examined by the immunoblotting procedure. Sera from infected mice recognized 51 antigen bands with apparent molecular masses from 8 to 86 kD. Sixteen of these were defined as major antigen bands because of almost universal presence of antibodies to them, and their intense staining. All sera, including those from normal control mice, tested for both IgM and IgG antibody reacted with the major E antigen which appeared as a large diffuse band from 43 to 47 kD. Comparisons between resistant and susceptible mice showed some significant differences in IgM responses to many antigen bands. While IgG responses were quite similar for both strains, differences were apparent in the response to the antigens at 62 and 68 kD. Images Fig. 1 Fig. 2 Fig. 3 PMID:1563097

  14. Immunological properties of isolated IgG and IgM anti-gamma-globulins (rheumatoid factors)*

    PubMed Central

    Bianco, N. E.; Dobkin, Linda W.; Schur, P. H.

    1974-01-01

    Anti-gamma-globulins of the IgG and IgM classes have been isolated from sera of normal individuals and from patients with osteoarthritis, rheumatoid arthritis and juvenile rheumatoid arthritis. All of the isolated antibodies gave precipitin curves with heat-aggregated, reduced and alkylated gamma-globulin. IgM anti-gamma-globulins gave a positive latex fixation test at 4°C and 37°C while IgG anti-gamma-globulins generally gave a positive test only at 4°C. Anti-gamma-globulins from normals did not fix complement but IgG and IgM anti-gamma-globulins from rheumatoids fixed complement to a similar degree. This in vitro complement fixation could account at least in part for the diminished complement levels seen in many rheumatoid synovial effusions. PMID:4466600

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

    PubMed

    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.

  16. IRAK-4 and MyD88 deficiencies impair IgM responses against T-independent bacterial antigens

    PubMed Central

    Maglione, Paul J.; Simchoni, Noa; Black, Samuel; Radigan, Lin; Overbey, Jessica R.; Bagiella, Emilia; Bussel, James B.; Bossuyt, Xavier; Casanova, Jean-Laurent; Meyts, Isabelle; Cerutti, Andrea; Picard, Capucine

    2014-01-01

    IRAK-4 and MyD88 deficiencies impair interleukin 1 receptor and Toll-like receptor (TLR) signaling and lead to heightened susceptibility to invasive bacterial infections. Individuals with these primary immunodeficiencies have fewer immunoglobulin M (IgM)+IgD+CD27+ B cells, a population that resembles murine splenic marginal zone B cells that mount T-independent antibody responses against bacterial antigens. However, the significance of this B-cell subset in humans is poorly understood. Using both a 610 carbohydrate array and enzyme-linked immunosorbent assay, we found that patients with IRAK-4 and MyD88 deficiencies have reduced serum IgM, but not IgG antibody, recognizing T-independent bacterial antigens. Moreover, the quantity of specific IgM correlated with IgM+IgD+CD27+ B-cell frequencies. As with mouse marginal zone B cells, human IgM+CD27+ B cells activated by TLR7 or TLR9 agonists produced phosphorylcholine-specific IgM. Further linking splenic IgM+IgD+CD27+ B cells with production of T-independent IgM, serum from splenectomized subjects, who also have few IgM+IgD+CD27+ B cells, had reduced antibacterial IgM. IRAK-4 and MyD88 deficiencies impaired TLR-induced proliferation of this B-cell subset, suggesting a means by which loss of this activation pathway leads to reduced cell numbers. Thus, by bolstering the IgM+IgD+CD27+ B-cell subset, IRAK-4 and MyD88 promote optimal T-independent IgM antibody responses against bacteria in humans. PMID:25320238

  17. IRAK-4 and MyD88 deficiencies impair IgM responses against T-independent bacterial antigens.

    PubMed

    Maglione, Paul J; Simchoni, Noa; Black, Samuel; Radigan, Lin; Overbey, Jessica R; Bagiella, Emilia; Bussel, James B; Bossuyt, Xavier; Casanova, Jean-Laurent; Meyts, Isabelle; Cerutti, Andrea; Picard, Capucine; Cunningham-Rundles, Charlotte

    2014-12-04

    IRAK-4 and MyD88 deficiencies impair interleukin 1 receptor and Toll-like receptor (TLR) signaling and lead to heightened susceptibility to invasive bacterial infections. Individuals with these primary immunodeficiencies have fewer immunoglobulin M (IgM)(+)IgD(+)CD27(+) B cells, a population that resembles murine splenic marginal zone B cells that mount T-independent antibody responses against bacterial antigens. However, the significance of this B-cell subset in humans is poorly understood. Using both a 610 carbohydrate array and enzyme-linked immunosorbent assay, we found that patients with IRAK-4 and MyD88 deficiencies have reduced serum IgM, but not IgG antibody, recognizing T-independent bacterial antigens. Moreover, the quantity of specific IgM correlated with IgM(+)IgD(+)CD27(+) B-cell frequencies. As with mouse marginal zone B cells, human IgM(+)CD27(+) B cells activated by TLR7 or TLR9 agonists produced phosphorylcholine-specific IgM. Further linking splenic IgM(+)IgD(+)CD27(+) B cells with production of T-independent IgM, serum from splenectomized subjects, who also have few IgM(+)IgD(+)CD27(+) B cells, had reduced antibacterial IgM. IRAK-4 and MyD88 deficiencies impaired TLR-induced proliferation of this B-cell subset, suggesting a means by which loss of this activation pathway leads to reduced cell numbers. Thus, by bolstering the IgM(+)IgD(+)CD27(+) B-cell subset, IRAK-4 and MyD88 promote optimal T-independent IgM antibody responses against bacteria in humans.

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

    PubMed

    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.

  19. The bovine lymphoid system. III. A monoclonal antibody specific for bovine cell surface and serum IgM.

    PubMed Central

    Pinder, M; Musoke, A J; Morrison, W I; Roelants, G E

    1980-01-01

    Mouse spleen cells from animals immunized with bovine peripheral blood lymphocytes were fused to X63 . Ag8 myeloma cells and the activity of one of the resulting myeloma hybrids was characterized. The product of this clone (B5/4.1.4) binds to pentameric bovine IgM isolated from serum but not to serum IgG1 or IgG2. This reagent also binds to cell surface (monomeric) IgM and can be used in immunofluorescence assays to enumerate IgM-bearing cells in lymphoid cell suspensions and to examine B lymphocytes or B lymphocyte derived cells in tissue sections. Images Figure 4 PMID:7000680

  20. Mapping of the X linked form of hyper IgM syndrome (HIGM1)

    PubMed

    Padayachee, M; Levinsky, R J; Kinnon, C; Finn, A; McKeown, C; Feighery, C; Notarangelo, L D; Hendriks, R W; Read, A P; Malcolm, S

    1993-03-01

    X linked immunodeficiency with hyperimmunoglobulinaemia M (HIGM1), which is characterised by agammaglobulinaemia together with excess IgM production reflecting an impairment of the immunoglobulin heavy chain class switch of B lymphocytes, has been mapped to Xq26. We report multipoint linkage data in six families with HIGM1 which show that the most likely position for the gene is close to HPRT with a maximum lod score of 4.89. The finding of recombinations between HIGM1 and both HPRT and DXS42 implies that HIGM1 is not allelic to X linked lymphoproliferative disease. These data will be useful in genetic counselling in families and will also be useful in testing candidate genes.

  1. Call admission control for CDMA systems with Interference Guard Margin (IGM)

    NASA Astrophysics Data System (ADS)

    Chen, Huan; Kumar, Sunil; Kuo, C.-C. Jay

    2002-01-01

    A call admission control (CAC) scheme and a resource-reservation estimation (RRE) method suitable for the interference-based wireless system, such as wide-band code division multiple access (W-CDMA), are proposed in this work. The proposed CAC scheme gives preferential treatment to high priority handoff calls by pre-reserving a certain amount of interference margin called the interference guard margin (IGM). The amount of guard margin is determined by the measurement performed by the RRE module in base stations. Each RRE module dynamically adjusts the level of guard margin by considering traffic conditions in neighboring cells based upon handoff requests. A service model is adopted to support multiple services, which includes mobile terminal's data rate, different levels of priorities, mobility and rate adaptivity characteristics. Simulations are conducted with OPNET to study the performance of the proposed scheme in terms of the objective function, blocking probabilities and system utilization under different traffic conditions.

  2. Binding properties of goat IgM anti-dinitrophenyl antibodies.

    PubMed Central

    Congy, N; Mihaesco, C

    1978-01-01

    Goats immunized over 2 months with low doses of 1 mg/kg of dinitrophenylated Salmonella typhimurium responded with low levels of anti-DNP antibodies restricted to the IgM class. The purified antibodies show low association constants (Ka between 10(4) of 10(5) l/M), a high degree of homogeneity (heterogeneity indices alpha between 0.7 and 0.9) and ten combining sites when tested against dinitrophenyl-lysine as ligand by equilibrium dialysis. These binding properties remained unchanged during the whole immune response. When after 9 months the animals received the same immunogen and DNP-BGG, the anti-DNP antibody response included antibodies in the IgG class. Images Figure 3 PMID:86504

  3. Classical and lectin complement pathway activity in polyneuropathy associated with IgM monoclonal gammopathy.

    PubMed

    Stork, Abraham C J; Cats, Elisabeth A; Vlam, Lotte; Heezius, Erik; Rooijakkers, Suzan; Herpers, Bjorn; de Jong, Ben A W; Rijkers, Ger; van Strijp, Jos; Notermans, Nicolette C; van den Berg, Leonard H; van der Pol, W-Ludo

    2016-01-15

    Polyneuropathy associated with IgM monoclonal gammopathy (IgM-PNP) is a slowly progressive, sensorimotor neuropathy. It is assumed that complement activation contributes to IgM-PNP pathogenesis. We investigated whether innate differences in complement activity of the classical and mannose binding lectin (MBL) pathways are associated with IgM-PNP or its severity. We measured complement activity using ELISA and determined MBL serumc oncentrations and MBL gene polymorphisms in 83 patients and 83 healthy controls. We did not observe differences between IgM-PNP patients and healthy controls nor associations with different disease severities. Differences in innate complement activity are not likely to explain susceptibility to or severity of IgM-PNP.

  4. Reduced secreted mu mRNA synthesis in selective IgM deficiency of Bloom's syndrome.

    PubMed Central

    Kondo, N; Ozawa, T; Kato, Y; Motoyoshi, F; Kasahara, K; Kameyama, T; Orii, T

    1992-01-01

    Serum IgM concentrations were low although serum IgG and IgA concentrations were normal in both our patients with Bloom's syndrome. Although the percentages of surface IgM-bearing cells were not reduced, the numbers of IgM-secreting cells were markedly reduced. The membrane-bound mu (microns) and secreted mu (microseconds) mRNAs are produced from transcripts of a single immunoglobulin mu gene by alternative RNA processing pathways. The control of microseconds mRNA synthesis depends on the addition of poly(A) to microseconds C-terminal segment. In both patients, mu mRNA was well detected but microseconds C-terminal mRNA was scarcely detected, suggesting that microns mRNA was well transcribed but microseconds mRNA was not. There was, at least, no mutation or deletion in the microseconds C-terminal coding sequence, the RNA splice site (GG/TAAAC) at the 5' end of microseconds C-terminal segment and the AATAAA poly(A) signal sequence in both patients. Our results suggest that selective IgM deficiency in Bloom's syndrome is due to an abnormality in the maturation of surface IgM-bearing B cells into IgM-secreting cells and a failure of microseconds mRNA synthesis. Moreover, reduced microseconds mRNA synthesis may be due to the defect on developmental regulation of the site at which poly(A) is added to transcripts of the mu gene. Images Fig. 2 PMID:1563106

  5. Production and characterization of monoclonal antibodies to IgM of Pacific herring (Clupea pallasii).

    PubMed

    Purcell, Maureen K; Bromage, Erin S; Silva, Jessica; Hansen, John D; Badil, Samantha M; Woodson, James C; Hershberger, Paul K

    2012-09-01

    Pacific herring (Clupea pallasii) have a central role in the North Pacific ecosystem as a forage fish species and are natural reservoirs of several important finfish pathogens, including Viral hemorrhagic septicemia virus (VHSV). Here, we report the identification of the gene encoding the immunoglobulin mu (IgM) heavy chain, as well as the development and characterization of monoclonal antibodies (MAbs) that specifically react with Pacific herring IgM. Pacific herring immunoglobulin was purified and consisted of heavy and light chains of approximately 80 and 25 kDa. Three hybridoma clones were initially identified by ELISA as reactive with purified immunoglobulin but only one clone was able to detect an 80 kDa protein in Pacific and Atlantic herring (Clupea harengus) whole plasma by denaturing western blot. However, all three MAbs were able to precipitate an 80 kDa protein from Pacific herring and LCMS sequencing of peptide fragments derived from this protein matched the predicted amino acid sequence of the cloned, heavy chain gene. In addition, two of the MAbs stained cells within the putative lymphocyte gates for the spleen, anterior kidney and posterior kidney but were not reactive for myeloid/granulocyte gates, which is consistent with these MAbs reacting with surface IgM⁺ B-cells. To our knowledge, this is the first report of IgM-related gene sequences and anti-IgM monoclonal antibodies from any member of the family Clupeidae. The antibodies produced in this study are critical for achieving our long-term goal of conducting serological surveillance to assess pathogen exposure in natural populations of Pacific herring.

  6. Raman spectroscopy-based screening of IgM positive and negative sera for dengue virus infection

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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.

  8. A clinical and neurobiological case of IgM NMDA receptor antibody associated encephalitis mimicking bipolar disorder.

    PubMed

    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.

  9. High seroprevalence of Mycoplasma pneumoniae IgM in acute Q fever by enzyme-linked immunosorbent assay (ELISA).

    PubMed

    Lai, Chung-Hsu; Chang, Lin-Li; Lin, Jiun-Nong; Chen, Wei-Fang; Kuo, Li-Li; Lin, Hsi-Hsun; Chen, Yen-Hsu

    2013-01-01

    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.

  10. Chimeric human/murine monoclonal IgM antibodies to HIV-1 Nef antigen expressed on chronically infected cells.

    PubMed

    Kawai, Masahiro; He, Lianying; Kawamura, Takeshi; Omoto, Shinya; Fujii, Yoichi R; Okada, Noriko

    2003-01-01

    Human IgM antibody (Ab) to gangliosides induced cytolysis of HIV-1-infected cells by homologous human complement. We expected that any human IgM Ab reactive with HIV-1 infected cells could cause complement-mediated cytolysis. The trans-chromosome mouse (TC mouse) contains human chromosomes harboring genes responsible for immunoglobulin production. Spleen cells from TC mice immunized with recombinant Nef were fused with mouse myeloma cells to generate hybridomas, and we selected those that produced human mu-chain-positive Abs reactive with Nef fixed on an ELISA plate. However, the L-chain of the monoclonal Abs (mAbs) were murine lambda in type and were chimeric, and we could not succeed in obtaining mAb with human mu- and human kappa-chains. The chimeric mAbs reacted with the HIV-1 infected cells as seen with flow cytometric analysis, and the surface expression of Nef was also detectable on chronically infected OM10.1 cells which had no detectable gp120. However, although the reaction of the chimeric IgM mAb with HIV-1-infected MOLT4 cells induced C3 deposition on cell surfaces on incubation with fresh human serum, the cells remained unlysed, as determined by 51Cr release assay. The amount of Nef antigen on the cells might not have been high enough to overcome the function of HRF20 (CD59) that restricts formation of membrane attack complexes of homologous complement. However, combination of anti-Nef IgM mAb with other IgM mAbs reactive with the surface of HIV-1-infected cells may induce a synergistic effect in complement mediated cytolysis.

  11. IgD, like IgM, is a primordial immunoglobulin class perpetuated in most jawed vertebrates.

    PubMed

    Ohta, Yuko; Flajnik, Martin

    2006-07-11

    IgD has remained a mysterious Ig class and a bane to immunology students since its discovery >40 years ago. Its spotty occurrence in mammals and birds and the discovery of an isotype with similarities to IgD in bony fish are perplexing. We have identified IgD heavy (H) chain (delta) from the amphibian Xenopus tropicalis during examination of the IgH locus. The Xenopus delta gene is in the same position, immediately 3' of the IgM gene, as in mammals, and it is expressed only in the spleen at low levels, primarily as a transmembrane receptor by surface IgM(+) cells. Our data suggest that frog IgD is expressed on mature B cells, like in mouse/human. Unexpectedly, Xenopus IgD is orthologous to IgW, an Ig isotype found only in cartilaginous fish and lungfish, demonstrating that IgD/W, like IgM, was present in the ancestor of all living jawed vertebrates. In striking contrast to IgM, IgD/W is evolutionarily labile, showing many duplications/deletions of domains, the presence of multiple splice forms, existence as predominantly a secretory or transmembrane form, or loss of the entire gene in a species-specific manner. Our study suggests that IgD/W has played varied roles in different vertebrate taxa since the inception of the adaptive immune system, and it may have been preserved as a flexible locus over evolutionary time to complement steadfast IgM.

  12. rROP2186–533: A Novel Peptide Antigen for Detection of IgM Antibodies Against Toxoplasma gondii

    PubMed Central

    Liu, Lili; Liu, Tingting; Yu, Li; Cai, Yihong; Zhang, Aimei; Xu, Xiucai; Luo, Qingli; Hu, Yuansheng; Song, Wenjian; Lun, Zhaorong; Lu, Fangli; Wang, Yong

    2012-01-01

    Abstract Toxoplasma gondii infections are prevalent in a wide range of mammalian hosts including humans. Infection in pregnant women may cause the transmission of parasite to the fetus that makes serious problems. IgM antibodies against Toxoplasma (Toxo-IgM) have been believed to be significant indicators for both recently acquired and congenital toxoplasmosis. So far, however, there has not been any recognized protein of T. gondii that specifically reacts to IgM antibodies. Here, an antigen exclusively for detection of IgM antibodies screened by two-dimensional electrophoresis and mass spectrometry has been reported. The study identified 13 Toxoplasma proteins probed by IgG antibodies and one (rhpotry protein 2 [ROP2]) by IgM antibodies with human sera of Toxo-IgM–-IgG+ and -IgM+-IgG–, respectively, which had been prescreened by Toxo-IgM and -IgG commercial kits from the suspected cases. Following cloning, expression, and purification of the fragment of ROP2186–533, an enzyme-linked immunosorbent assay with rROP2186–533 to measure IgM and IgG antibodies was developed. As a result, 100%(48/48) of sera with Toxo-IgM+-IgG–showed positive Toxo-IgM but none of them (0%) showed positive Toxo-IgG when rROP2186–533 was used as antigen. Neither Toxo-IgG nor Toxo-IgM antibodies were found when tested with 59 sera of Toxo-IgM–-IgG+. These results indicate that rROP2186–533 could be used as an antigen that specifically capture Toxo-IgM antibodies and may have a high potential in the serological diagnosis of both acute acquired and congenital toxoplasmosis. PMID:22085219

  13. Variable region sequences of murine IgM anti-IgG monoclonal autoantibodies (rheumatoid factors). A structural explanation for the high frequency of IgM anti-IgG B cells

    PubMed Central

    1986-01-01

    The nucleotide sequences of heavy and light chains from 10 monoclonal IgM anti-IgG1 (RF) antibodies were determined and reported here as translated amino acid sequences. Only three families of VK light chains were used in these antibodies: VK1 (two examples), VK8 (three examples), and VK19 (four examples). This represents a significant nonrandom selection of light chains. In contrast, all other variable region gene segments (i.e., VH, DH, JH, and JK) were used in a pattern consistent with random selection from the available pool of germline genes. In two cases, the same anti-IgG1 specificity was generated by a combination of very homologous light chains with unrelated heavy chains. We infer from this that the light chain is the segment used by these antibodies to bind IgG1. The nature of these sequences provides an explanation for the curious observation that as many as 15% of splenic B cells in normal mice may be expressing IgM anti-IgG; if, as our data suggest, certain light chains in combination with many different heavy chains can be used in assembling the anti-IgG specificity, then, because of combinatorial association in which the heavy chain is not relevant for specificity, the fraction of IgM- producing B cells expressing these light chains should approximate the fraction of B cells making IgM anti-IgG. We calculate, based on data presented in several other studies, that 5-17% of B cells express one of the VK types observed in monoclonal RF. This agrees well with estimates for the number of B cells making IgM anti-IgG. In addition, our findings could rule out other explanations of the high percentage of B cells making RF, such as constant stimulation by antigen or presence of numerous antigenic epitopes since it was shown that IgM anti-IgG1 antibodies are not somatically mutated and that they are structurally homogeneous. We aligned the VK sequences of the RF in hopes of finding some primary sequence homology between the represented VK families which might

  14. Diagnosing ALS

    MedlinePlus

    ... that a person diagnosed with ALS seek a second opinion from an ALS "expert" - someone who diagnoses and treats many ALS patients and has training in this medical specialty. The ALS Association maintains a list of recognized experts in the field of ALS. See ALS Association Certified Centers of ...

  15. Naturally occurring IgM antibodies to oxidation-specific epitopes.

    PubMed

    Binder, Christoph J

    2012-01-01

    Naturally occurring antibodies (NAbs) have specificity for both microbial and self antigens, which allows them to act in the first line defense against invading pathogens, as well as in tissue homeostasis by mediating the clearance of cellular debris. This latter recognition of self by NAbs was often thought to reflect the polyreactivity of low affinity antibodies. The finding that oxidation-specific epitopes are dominant targets of naturally occurring IgM antibodies shed light on this and provided novel insights into the understanding of the house keeping functions of NAbs. Oxidation-specific epitopes represent stress-induced or altered self structures that are generated as a consequence of lipidperoxidation during many physiological and pathological situations. Importantly, the same structures have been found in the membranes of dying cells. Only oxidized lipids and dying cells-but not native membrane lipids or viable cells-are recognized by this set of NAbs. Thus, oxidation-specific epitopes represent ideal marks that identify biological waste for its clearance and the neutralization of its pro-inflammatory properties. Furthermore, this binding property of NAbs has also important implications for various chronic inflammatory diseases, including atherosclerosis.

  16. Radio resource management for CDMA systems with interference guard margin (IGM)

    NASA Astrophysics Data System (ADS)

    Chen, Huan; Kumar, Sunil; Kuo, C.-C. Jay

    2001-11-01

    A call admission control (CAC) scheme and a resource reservation estimation (RRE) method suitable for the wide-band code division multiple access (W-CDMA) systems are proposed in this work. The proposed CAC scheme gives preferential treatment to high priority calls, such as handoff calls, by pre-reserving a certain amount of channel margin against the interference effect. It is called the interference guard margin (IGM) scheme. The amount of guard margin is determined by the measurement performed by the RRE module in base stations. Each RRE module dynamically adjusts the level of guard margin by referencing traffic conditions in neighboring cells based upon users' requests. A comprehensive service model is adopted to accommodate the scenario of multiple services supported in the W-CDMA system. The service model of consideration includes not only mobile terminal's service rate (source rate) but also different levels of priorities, mobility and rate adaptivity characteristics. Simulations are conducted with OPNET to study the performance of the proposed scheme in term of the objective function under different traffic conditions.

  17. Physical biochemical properties of IgM from a teleost fish.

    PubMed Central

    Mochida, K; Lou, Y H; Hara, A; Yamauchi, K

    1994-01-01

    Teleost fish are able to produce IgM class antibody, as are other vertebrates. When the teleost fish Oreochromis niloticus was immunized with bovine serum albumin (BSA), it produced antibody to BSA with an average avidity of 7.4 x 10(8)/M. Thus, dissociation of antigen-antibody complexes only occurred at conditions of < pH 2.5, > pH 11, > 4M NaI or > 4M urea, demonstrating high stability of the complex. Western blot analyses further showed the high specificity of the antibody to BSA. In contrast to mammals, when the fish was challenged with multiple protein antigens, it produced antibody only to the major component but not to others. The antibody generated to a specific antigen accounted for up to 1.1% of whole serum protein or 7.0% of whole immunoglobulin. We conclude (1) the systemic antibody response in teleost fish may be an 'all or nothing' response, which is different from that in mammals; (2) the quality (specificity and affinity) of the antibody produced is similar to that of mammals. The findings not only reveal a quite different strategy of immune response in fish, but also raise the possibility of technical application. Images Figure 2 Figure 3 PMID:7875748

  18. Comparison of automated chemiluminescence immunoassays with capture enzyme immunoassays for the detection of measles and mumps IgM antibodies in serum.

    PubMed

    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. Large-scale purification of IgM from human sera. Comparison of three optimized procedures utilizing protein A chromatography.

    PubMed

    Mauch, H; Kümel, G; Hammer, H J

    1980-01-01

    for the preparation of gram amounts of IgM from human sera sedimentation at 100,000 g or treatment with ZnSO4 of the redissolved "euglobulin"-precipitate was compared to direct precipitation from the clarified serum by boric acid. Three alternative large scale purification procedures were developed, leading to an IgM-sample characterized as pure by various criteria. Inclusion of protein A chromatography proved to enhance the yield very considerably.

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

    PubMed Central

    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

  1. Natural IgM Blockade Limits Infarct Expansion and Left Ventricular Dysfunction in a Swine Myocardial Infarct Model

    PubMed Central

    Sihag, Smita; Haas, Michael S.; Kim, Karen M.; Guerrero, J. Luis; Beaudoin, Jonathan; Alicot, Elisabeth M.; Schuerpf, Franziska; Gottschall, James D.; Puro, Robyn J.; Madsen, Joren C.; Sachs, David H.; Newman, Walter; Carroll, Michael C.; Allan, James S.

    2015-01-01

    Background Acute coronary syndrome is the leading cause of mortality worldwide. However, treatment of acute coronary occlusion inevitably results in ischemia-reperfusion (I/R) injury. Circulating natural IgM has been shown to play a significant role in mouse models of I/R injury. A highly conserved self-antigen, non-muscle myosin heavy chain II (NMHC-II), has been identified as a target of pathogenic IgM. We hypothesized that a monoclonal antibody (m21G6) directed against NMHC-II may inhibit IgM binding and reduce injury in a pre-clinical model of myocardial infarction (MI). Thus, our objective was to evaluate the efficacy of intravenous m21G6 treatment in limiting infarct expansion, troponin release, and left ventricular dysfunction in a swine MI model. Methods and Results MGH miniature swine underwent occlusion of the mid left anterior descending coronary artery for 60min, followed by 1h, 5d, or 21d reperfusion. Specificity and localization of m21G6 to injured myocardium were confirmed using fluorescently labeled m21G6. Treatment with m21G6 prior to reperfusion resulted in a 49% reduction in infarct size (p<0.005) and a 61% reduction in troponin-T levels (p<0.05) in comparison to saline controls at 5d reperfusion. Furthermore, m21G6 treated animals recovered 85.4% of their baseline left ventricular function as measured by two-dimensional transthoracic echocardiography (2D TTE) in contrast to 67.1% in controls at 21d reperfusion (p<0.05). Conclusions Treatment with m21G6 significantly reduced infarct size and troponin-T release, and led to marked preservation of cardiac function in our study. Overall, these findings suggest that pathogenic IgM blockade represents a valid therapeutic strategy in mitigating myocardial I/R injury. PMID:26671971

  2. Crystal structure of a glycosylated Fab from an IgM cryoglobulin with properties of a natural proteolytic antibody.

    PubMed

    Ramsland, Paul A; Terzyan, Simon S; Cloud, Gwendolyn; Bourne, Christina R; Farrugia, William; Tribbick, Gordon; Geysen, H Mario; Moomaw, Carolyn R; Slaughter, Clive A; Edmundson, Allen B

    2006-05-01

    The 2.6 A (1 A=0.1 nm) resolution structure has been determined for the glycosylated Fab (fragment antigen binding) of an IgM (Yvo) obtained from a subject with Waldenström's macroglobulinaemia. Dynamic light scattering was used to estimate the gel point and monitor the formation of an ordered hydroscopic gel of Yvo IgM upon cooling. If a cryoglobulin forms gels in peripheral tissues and organs, the associated swelling and damage to microvasculature can result in considerable morbidity and mortality. The three-dimensional structure of the branched N-linked oligosaccharide associated with the CH1 domain (first constant domain of heavy chain) is reported. The carbohydrate may act to shield part of the lateral surface of the CH1 domain and crowd the junction between the CH1 and CH2 domains, thereby limiting the segmental flexibility of the Fab arms in intact Yvo IgM, especially at low temperatures. Recently, Yvo IgM was shown to have the properties of a naturally occurring proteolytic antibody [Paul, Karle, Planque, Taguchi, Salas, Nishiyama, Handy, Hunter, Edmundson and Hanson (2004) J. Biol. Chem. 279, 39611-39619; Planque, Bangale, Song, Karle, Taguchi, Poindexter, Bick, Edmundson, Nishiyama and Paul (2004) J. Biol Chem. 279, 14024-14032]. The Yvo protein displayed the ability to cleave, by a nucleophilic mechanism, the amide bonds of a variety of serine protease substrates and the gp120 coat protein of HIV. An atypical serine, arginine and glutamate motif is located in the middle of the Yvo antigen-binding site and displays an overall geometry that mimics the classical serine, histidine and aspartate catalytic triad of serine proteases. Our present findings indicate that pre-existing or natural antibodies can utilize at least one novel strategy for the cleavage of peptide bonds.

  3. Novel B cell population producing functional IgG in the absence of membrane IgM expression.

    PubMed

    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.

  4. [Rheumatoid factor activity as a disturbing factor in the serological diagnosis of specific IgM antibodies].

    PubMed

    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.

  5. Comparative study of immunochromatographic assay (IgM) and widal test for early diagnosis of typhoid fever.

    PubMed

    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.

  6. ALS Association

    MedlinePlus

    ... toward a world without ALS! Walk to Defeat ALS® Walk to Defeat ALS® draws people of all ... We need your help. I Will Advocate National ALS Registry The National ALS Registry is a congressionally ...

  7. Specificity and biologic activities of novel anti-membrane IgM antibodies

    PubMed Central

    Welt, Rachel S.; Welt, Jonathan A.; Kostyal, David; Gangadharan, Yamuna D; Raymond, Virginia; Welt, Sydney

    2016-01-01

    The concept that the B-cell Receptor (BCR) initiates a driver pathway in lymphoma-leukemia has been clinically validated. Previously described unique BCR Ig-class-specific sequences (proximal domains (PDs)), are not expressed in serum Ig (sIg). As a consequence of sequence and structural differences in the membrane IgM (mIgM) μ-Constant Domain 4, additional epitopes distinguish mIgM from sIgM. mAbs generated to linear and conformational epitopes, restricted to mIgM and not reacting with sIgM, were generated despite the relative hydrophobicity of the PDm sequence. Anti-PD mAbs (mAb1, mAb2, and mAb3) internalize mIgM. Anti-mIgM mAb4, which recognizes a distinct non-ligand binding site epitope, mediates mIgM internalization, and in low-density cultures, growth inhibition, anti-clonogenic activity, and apoptosis. We show that mAb-mediated mIgM internalization generally does not interrupt BCR-directed cell growth, however, mAb4 binding to a non-ligand binding site in the mIgM PDm-μC4 domain induces both mIgM internalization and anti-tumor effects. BCR micro-clustering in many B-cell leukemia and lymphoma lines is demonstrated by SEM micrographs using these new mAb reagents. mAb4 is a clinical candidate as a mediator of inhibition of the BCR signaling pathway. As these agents do not bind to non-mIgM B-cells, nor cross-react to non-lymphatic tissues, they may spare B-cell/normal tissue destruction as mAb-drug conjugates. PMID:27732950

  8. ABO (histo) blood group phenotype development and human reproduction as they relate to ancestral IgM formation: A hypothesis.

    PubMed

    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

  9. VIMOS Ultra-Deep Survey (VUDS): IGM transmission towards galaxies with 2.5 < z < 5.5 and the colour selection of high-redshift galaxies

    NASA Astrophysics Data System (ADS)

    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 < z < 5.5 in the VIMOS Ultra Deep Survey (VUDS). We fitted model spectra combined with a range of IGM transmission to the galaxy spectra using the spectral fitting algorithm GOSSIP+. We used these fits to derive the mean IGM transmission towards each galaxy for several redshift slices from z = 2.5 to z = 5.5. We found that the mean IGM transmission defined as Tr(Lyα) = e- τ (with τ as the HI optical depth) is 79%, 69%, 59%, 55%, and 46% at redshifts 2.75, 3.22, 3.70, 4.23, and 4.77, respectively. We compared these results to measurements obtained from quasar lines of 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

  10. Differential binding avidities of human IgM for staphylococcal protein A derive from specific germ-line VH3 gene usage.

    PubMed

    Hakoda, M; Kamatani, N; Hayashimoto-Kurumada, S; Silverman, G J; Yamanaka, H; Terai, C; Kashiwazaki, S

    1996-10-01

    Human IgM that express the variable region genes of the VH3 family bind staphylococcal protein A (SPA). We previously reported that the SPA-binding IgM can be divided into two groups based on the differential binding avidities for solid-phase SPA. To study the molecular basis for these differences, we cloned B cells from human blood by EBV transformation. The nucleotide sequences of the expressed Ig heavy chain genes were determined on 20 B cell clones that produce SPA-binding IgM. The germ-line VH3 gene usage in IgM with high avidities for SPA were distinct from the germ-line VH3 genes used in IgM with low avidities for SPA. There was no correlation in the usage of D or JH genes or in the usage of light chains in IgM according to the SPA binding avidity. These results suggest that the differential binding avidities for SPA are at least partly due to specific germ-line VH3 gene usage. An investigation of direct binding of SPA to the synthetic peptides corresponding to the portions of the variable regions of SPA-binding and non-SPA-binding IgM showed that the peptides corresponding to the VH3 family specific framework region 3 sequences had significant SPA binding capacities, while the peptides corresponding to the other subdomains and those corresponding to framework region 3 of the reported VH3 sequences from non-SPA-binding IgM showed little or no binding. It is of interest that the Ig-framework region 3 subdomain corresponds to the fourth hypervariable region, which in the TCR-beta chain has been implicated as a critical site for T cell superantigen binding.

  11. Waldenström's macroglobulinaemia in a bird breeder: a case history with pulmonary involvement and antibody activity of the monoclonal IgM to canary's droppings.

    PubMed Central

    James, J M; Brouet, J C; Orvoenfrija, E; Capron, F; Brechot, J; Danon, F; Diebold, J; Rochemaure, J; Zittoun, R

    1987-01-01

    A canary breeder with Waldenström's macroglobulinemia developed a pulmonary disease related to an interstitial infiltration by malignant B cells secreting a monoclonal IgM K. The serum monoclonal IgM was shown to possess an antibody activity to some canary's droppings antigen. This finding may help elucidate the natural course of lymphoid malignancies and the pathogenesis of rare visceral localizations. Images Fig. 1 Fig. 2 Fig. 3 PMID:3115646

  12. Anti Japanese encephalitis virus IgM positivity among patients with acute encephalitic syndrome admitted to different hospitals from all over Nepal

    PubMed Central

    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

  13. Anti Japanese encephalitis virus IgM positivity among patients with acute encephalitic syndrome admitted to different hospitals from all over Nepal.

    PubMed

    Bhattarai, Anupama; Pant, Narayan Dutt; 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.

  14. IgM and IgD concentrations in the serum and secretions of children with selective IgA deficiency.

    PubMed Central

    Plebani, A; Mira, E; Mevio, E; Monafo, V; Notarangelo, L D; Avanzini, A; Ugazio, A G

    1983-01-01

    Serum IgG and serum and secretory IgM, IgA and IgD levels were determined in 14 children with selective IgA deficiency and in 12 age and sex matched healthy controls. IgD was determined using a highly sensitive ELISA technique. In the healthy controls serum IgG, IgA and IgM were all in the age normal range, and serum IgA was significantly higher than secretory IgA with IgA in nasal secretions being significantly higher than in saliva. In the IgA deficient children serum IgG and IgM and secretory IgM were present in higher concentrations than in the controls but the difference was statistically significant only for serum IgG and salivary IgM. IgD was detectable in the serum and secretions of all patients and all but one control subject. Like IgM, serum IgD levels were significantly higher than secretory IgD levels and IgD was present in greater concentrations in nasal secretions than in saliva both in the patients and the controls, with no difference between the two groups. Thus, the data of this study show that while serum and secretory IgM levels are elevated in children with selective IgA deficiency, serum and secretory IgD are present in normal concentrations, supporting the hypothesis of a compensatory increase in IgM but not in IgD in such patients. PMID:6616961

  15. Fetal lambs are depleted of IgM+ cells following a single injection of an anti-IgM antibody early in gestation.

    PubMed Central

    Press, C M; Reynolds, J D; McClure, S J; Simpson-Morgan, M W; Landsverk, T

    1996-01-01

    B-cell depleted fetal sheep were created following a single injection of an anti-IgM monoclonal antibody early in gestation. Six sheep fetuses were given a single intraperitoneal injection of a monoclonal antibody directed against IgM at 63 days of gestation (gestation in sheep = 150 days). The fetuses were killed at 138-142 days of gestation and lymphoid tissues were collected for subsequent light microscopy and immunohistochemical examination. The ileal and jejunal Peyer's patch (PP) follicles in four of the six injected fetuses were markedly reduced in size. Cells in the rudimentary follicles of the ileal PP of these animals showed no reactivity for IgM and most were negative for CD45. The dome regions contained many T cells, which were predominantly CD8+ cells and included gamma delta T cells. The interfollicular areas of the PP of the markedly affected fetuses contained large populations of T cells. The spleen and lymph nodes were also markedly depleted of IgM+ cells and these tissues contained only a small, scattered population of weakly IgM+ cells. Follicular accumulations of IgM+ cells were absent. Large populations of T cells were present in the white pulp of the spleen and cortex of the lymph nodes. The liver did not contain IgM+ cells and the medulla of the thymus was depleted of IgM+ cells. The results of this study suggest that a surface IgM+ B-cell population is present in the sheep fetus at 63 days of gestation, which is essential for the colonization of the ileal PP and subsequent B-cell development. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8707346

  16. Low levels of natural IgM antibodies against phosphorylcholine are independently associated with vascular remodeling in patients with coronary artery disease.

    PubMed

    Gleissner, Christian A; Erbel, Christian; Haeussler, Julia; Akhavanpoor, Mohammadreza; Domschke, Gabriele; Linden, Fabian; Doesch, Andreas O; Conradson, Göran; Buss, Sebastian J; Hofmann, Nina P; Gitsioudis, Gitsios; Katus, Hugo A; Korosoglou, Grigorios

    2015-01-01

    Low anti-phosphorylcholine (PC) IgM plasma levels have been associated with increased incidence of adverse events in coronary artery disease (CAD). The underlying mechanisms are unclear. We hypothesized that atheroprotection mediated by anti-PC IgM antibodies is associated with reduced vascular remodeling and therefore tested whether anti-PC IgM plasma levels independently predict vascular remodeling. In a prospective cross-sectional study, anti-PC IgM plasma levels were measured in 175 consecutive patients with suspected CAD undergoing cardiac computed tomography angiography. Plaque morphology was thoroughly analyzed. Vascular remodeling was defined by a change in the vessel diameter at the plaque site in comparison to the reference segment proximal to the lesion (reference diameter) of ≥10%. Mean age of the patients was 64.8 ± 10.7 years, 48.6% were female. In 98 patients CAD was diagnosed, 57 (58.2%) of which displayed non-obstructive CAD (stenosis <50%), whereas 41 (41.8%) exhibited obstructive CAD (stenosis ≥50%). In 34 of 98 (34.7%) CAD patients vascular remodeling was present. Mean anti-PC IgM levels did not differ between patients with and without CAD (70.8 ± 52.7 vs. 69.1 ± 55.1 U/mL). However, anti-PC IgM levels were significantly lower in CAD patients compared to those without vascular remodeling (46.6 ± 31.6 vs. 73.3 ± 58.5 U/mL, P = 0.024). Using multivariate logistic regression, anti-PC IgM plasma levels independently predicted coronary vascular remodeling (HR 0.322, 95% confidence interval 0.121-0.856, P = 0.023). In conclusion, low anti-PC IgM levels are independently associated with coronary vascular remodeling. These findings may represent the link between in vitro studies demonstrating atheroprotective effects of anti-PC IgM and clinical data demonstrating that low anti-PC IgM levels are associated with adverse outcome in CAD patients.

  17. Efficacy of IgM anti-blood type antibody monitoring by enzyme-linked immunosorbent assay after renal transplantation across the blood barrier: high-dose immunoglobulin administration blocks IgM rather than IgG anti-blood type antibodies.

    PubMed

    Ishida, H; Tanabe, K; Furusawa, M; Isizuka, T; Tokumoto, T; Shimmura, H; Shimizu, T; Miyamoto, N; Hayashi, T; Toma, H

    2004-09-01

    We used an enzyme linked immunosorbent assay (ELISA) to investigate the presence of subtypes of anti-blood-type antibodies in patients with biopsy-proven humoral rejection after ABO-incompatible renal transplantation. High agglutinin IgG and IgM anti-blood type antibodies from 12 ABO-incompatible recipients with vascular rejection were separately assessed using an ELISA. Patients who exhibited excellent renal function despite high agglutinin titers of anti-blood-type antibodies(n = 8) were also examined. All 12 rejection patients exhibited highly elevated titers of IgG and IgM, while the eight stable patients exhibited only slightly elevated IgG titers, but not IgM. IgG and IgM titers did not change after plasmapheresis and steroid pulse therapy, whereas IVIg treatment significantly blocked both IgG and IgM, with IgM being blocked to a larger extent than IgG. Blocking of IgM seems to play an important role in improving ABO-incompatible grafts.

  18. Human polyreactive IgM monoclonal antibodies with blocking activity against self-reactive IgG.

    PubMed

    Melero, J; Tarragó, D; Núñez-Roldán, A; Sánchez, B

    1997-04-01

    Natural IgM antibodies have been found to be involved in the control of IgG reactivity in normal serum. The authors investigated the blocking activity of four human IgM monoclonal antibodies (BY-2, BY-7, BY-10 and IRM-7) derived from B-cells from blood samples of three renal dialysis patients, which had shown multispecific properties similar to those observed for natural polyreactive autoantibodies. To achieve this, competitive inhibition assays were performed with these MoAbs on the binding of IgG purified from a healthy control, three patients with SLE, and two patients with autoimmune thyroiditis, to histone, dsDNA, RNP and thyroglobulin. MoAbs inhibited binding of self-reactive IgG to histone and dsDNA, but not to thyroglobulin or RNP, of natural and active or inactive phase disease-associated autoreactive IgG. The inhibitory effect of the MoAbs was mediated by V-region dependent interactions with autoreactive IgG, as shown by the ability of these MoAbs to block the binding of F(ab')2 fragments of autoreactive IgG to antigens (histone and dsDNA). The blocking of autoantibody activity was dose-dependent with maximal inhibition occurring at a specific molar ratio between the patient's IgG and a given MoAb. In contrast, MoAbs did not inhibit binding of IgG alloantibodies present in the sera of four polytransfused renal dialysis patients to target antigens on the surface of different cells. These results support the concept of a functional idiotypic network regulating autoimmune responses, and suggest that the IgM MoAbs under study may be natural polyreactive antibodies belonging to the physiological network of autoantibodies with highly connected V-regions, capable of binding and functionally neutralizing V-regions of natural and pathologic autoantibodies.

  19. IGM CONSTRAINTS FROM THE SDSS-III/BOSS DR9 Lyα FOREST TRANSMISSION PROBABILITY DISTRIBUTION FUNCTION

    SciTech Connect

    Lee, Khee-Gan; Hennawi, Joseph F.; Spergel, David N.; Weinberg, David H.; Hogg, David W.; Viel, Matteo; Bolton, James S.; Bailey, Stephen; Carithers, William; Schlegel, David J.; Pieri, Matthew M.; Lundgren, Britt; Palanque-Delabrouille, Nathalie; Yèche, Christophe; Schneider, Donald P.

    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.

  20. An atypical IgM class platelet cold agglutinin induces GPVI-dependent aggregation of human platelets.

    PubMed

    Sánchez Guiu, I M; Martínez-Martinez, I; Martínez, C; Navarro-Fernandez, J; García-Candel, F; Ferrer-Marín, F; Vicente, V; Watson, S P; Andrews, R K; Gardiner, E E; Lozano, M L; Rivera, J

    2015-08-01

    Platelet cold agglutinins (PCA) cause pseudothrombocytopenia, spurious thrombocytopenia due to ex vivo platelet clumping, complicating clinical diagnosis, but mechanisms and consequences of PCA are not well defined. Here, we characterised an atypical immunoglobulin (Ig)M PCA in a 37-year-old woman with lifelong bleeding and chronic moderate thrombocytopenia, that induces activation and aggregation of autologous or allogeneic platelets via interaction with platelet glycoprotein (GP)VI. Patient temperature-dependent pseudothrombocytopenia was EDTA-independent, but was prevented by integrin αIIbβ3 blockade. Unstimulated patient platelets revealed elevated levels of bound IgM, increased expression of activation markers (P-selectin and CD63), low GPVI levels and abnormally high thromboxane (TX)A2 production. Patient serum induced temperature- and αIIbβ3-dependent decrease of platelet count in allogeneic donor citrated platelet-rich plasma (PRP), but not in PRP from Glanzmann's thrombasthenia or afibrinogenaemia patients. In allogeneic platelets, patient plasma induced shape change, P-selectin and CD63 expression, (14)C-serotonin release, and TXA2 production. Activation was not inhibited by aspirin, cangrelor or blocking anti-Fc receptor (FcγRIIA) antibody, but was abrogated by inhibitors of Src and Syk, and by a soluble GPVI-Fc fusion protein. GPVI-deficient platelets were not activated by patient plasma. These data provide the first evidence for an IgM PCA causing platelet activation/aggregation via GPVI. The PCA activity persisted over a five-year follow-up period, supporting a causative role in patient chronic thrombocytopenia and bleeding.

  1. International standards for IgG and IgM anti-β2glycoprotein antibody measurement.

    PubMed

    Willis, R; Grossi, C; Orietta Borghi, M; Martos-Sevilla, G; Zegers, I; Sheldon, J; Meroni, P L

    2014-10-01

    International standards for anti-beta2 glycoprotein I (anti-β2GPI) testing are needed. We evaluated the suitability of polyclonal/monoclonal candidate reference materials (RM) for the assay. IgG/IgM anti-β2GPI were affinity-purified (AP) from high-positive antiphospholipid syndrome sera and IgG from HCAL clone supernatant. Igs were tested for purity by SDS-PAGE, pooled, concentrated, sterile-filtered and the protein concentration determined. One unit was defined as the binding activity of 1 µg/ml of AP anti-β2GPI Ig. IgG/IgM RM were each assigned a unit value using the respective AP material as a calibrator. Polyclonal/monoclonal RM and 30 samples were evaluated for linearity, unit equivalency and commutability. Polyclonal AP material was assigned a value of 100 U IgG and 15 U IgM anti-β2GPI, respectively. IgG-RM had a value of 270 IgG and the IgM-RM of 220.3 IgM anti-β2GPI U. The linearity (R (2)) of each RM curve for the various assays ranged from 0.96 to 0.99. Commutability samples fit very well within 95% prediction intervals and had excellent correlation when comparing assays. IgG and IgM polyclonal and IgG monoclonal RM displayed excellent linearity and commutability, being good candidates for better standardization of anti-β2GPI immunoassays.

  2. Generation and Characterization of Antibodies against Asian Elephant (Elephas maximus) IgG, IgM, and IgA

    PubMed Central

    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. PMID:25658336

  3. HLA-DQBl*0402 alleles polymorphisms detected in Javanese HIV patients with positive anti-Toxoplasma gondii IgM

    NASA Astrophysics Data System (ADS)

    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.

  4. Performance on immunoglobulin IgG, IgA, and IgM tests in CAP survey specimens.

    PubMed

    Ritchie, R F; Rippey, J H

    1982-10-01

    The performance of participants in nine consecutive College of American Pathologists (CAP) Survey specimens during 1979-1981 are listed for IgA, IgG, and IgM. The majority of participants used either radial immunodiffusion (RID) (51.4%) or nephelometric kits (33.6 per cent) manufactured by major firms and reported results in mass units (93.5 per cent). When tabulated by kit, prominent differences in performance were noticed. Furthermore, definite trends in methods employed were evident during the two-year period.

  5. ALS - resources

    MedlinePlus

    Resources - ALS ... The following organizations are good resources for information on amyotrophic lateral sclerosis : Muscular Dystrophy Association -- www.mda.org/disease/amyotrophic-lateral-sclerosis National Amyotrophic Lateral Sclerosis (ALS) ...

  6. Rapid Proliferation and Differentiation of a Subset of Circulating IgM Memory B Cells to a CpG/Cytokine Stimulus In Vitro.

    PubMed

    Vásquez, Camilo; Franco, Manuel A; Angel, Juana

    2015-01-01

    Circulating human IgM expressing memory B cells have been incompletely characterized. Here, we compared the phenotype and in vitro functional response (capacity to proliferate and differentiate to antibody secreting cells) in response to CpG and a cytokine cocktail (IL-2, IL-6, and IL-10) of sorted naïve B cells, IgM memory B cells and isotype-switched circulating memory B cells. Compared to naïve B cells, IgM memory B cells had lower integrated mean fluorescence intensity (iMFI) of BAFF-R, CD38, CD73, and IL-21R, but higher iMFI of CD95, CD11c, TLR9, PD-1, and CD122. Compared to switched memory B cells, IgM memory B cells had higher iMFI of BAFF-R, PD-1, IL-21R, TLR9, and CD122, but lower iMFI of CD38, CD95, and CD73. Four days after receiving the CpG/cytokine cocktail, higher frequencies of IgM than switched memory B cells-and these in turn greater than naïve cells-proliferated and differentiated to antibody secreting cells. At this time point, a small percentage (median of 7.6%) of stimulated IgM memory B cells changed isotype to IgG. Thus, among the heterogeneous population of human circulating IgM memory B cells a subset is capable of a rapid functional response to a CpG/cytokine stimulus in vitro.

  7. Diagnosis of Dengue Virus Infection by Detection of Specific Immunoglobulin M (IgM) and IgA Antibodies in Serum and Saliva

    PubMed Central

    Balmaseda, Angel; Guzmán, María G.; Hammond, Samantha; Robleto, Guillermo; Flores, Carolina; Téllez, Yolanda; Videa, Elsa; Saborio, Saira; Pérez, Leonel; Sandoval, Erick; Rodriguez, Yoryelin; Harris, Eva

    2003-01-01

    To evaluate alternative approaches to the serological diagnosis of dengue virus (DEN) infection, the detection of DEN-specific immunoglobulin M (IgM) and IgA antibodies in serum and saliva specimens was assessed in 147 patients with symptoms of DEN infection seen at the Ministry of Health in Nicaragua. Seventy-two serum samples were determined to be positive for anti-DEN antibodies by IgM capture enzyme-linked immunosorbent assay, the routine diagnostic procedure. Serum and saliva specimens were obtained from 50 healthy adults as additional controls. IgM was detected in the saliva of 65 of the 72 serum IgM-positive cases, 6 of the 75 serum IgM-negative cases, and none of the control group, resulting in a sensitivity of 90.3% and a specificity of 92.0% and demonstrating that salivary IgM is a useful diagnostic marker for DEN infection. Detection of IgA in serum may be another feasible alternative for the diagnosis of DEN infection, with serum IgA found in 68 (94.4%) of the IgM-positive cases. In contrast, detection of IgA in saliva was not found to be a useful tool for DEN diagnosis in the present study. Further studies of the kinetics of antibody detection in another set of 151 paired acute- and convalescent-phase serum samples showed that DEN-specific IgA antibodies were detected in more acute-phase samples than were IgM antibodies. Thus, we conclude that DEN-specific IgA in serum is a potential diagnostic target. Furthermore, given that saliva is a readily obtainable, noninvasive specimen, detection of DEN-specific salivary IgM should be considered a useful, cheaper diagnostic modality with similar sensitivity and specificity to IgM detection in serum. PMID:12626461

  8. Simultaneous expression of Borrelia OspA and OspC and IgM response in cerebrospinal fluid in early neurologic Lyme disease.

    PubMed Central

    Schutzer, S E; Coyle, P K; Krupp, L B; Deng, Z; Belman, A L; Dattwyler, R; Luft, B J

    1997-01-01

    Lyme disease is the major tick-borne disease, caused by Borrelia burgdorferi (Bb). Neurological involvement is common in all stages. In vivo expression of Bb antigens (Ags) and the immune response to them has not been well investigated in the cerebrospinal fluid (CSF). Upregulation of outer surface protein (Osp) C and concomitant downregulation of OspA before tick inoculation of the spirochete has been reported in skin and blood in animals. CSF OspA Ag in early disease suggests otherwise in CSF. Early Ag expression and IgM response in human CSF was investigated here. Paired CSF and serum was collected from 16 early, predominantly erythema migrans Lyme disease patients with neurologic problems, 13 late Lyme disease patients, and 19 other neurologic disease (OND) controls. Samples were examined for IgM reactivity to recombinant Bb-specific Osps using ELISA and immunoblot. Of 12 early Lyme disease patients with neurologic involvement with both CSF and serum IgM against OspC, 7 (58%) had IgM to OspA (n = 5) or OspB (n = 2) that was restricted to the CSF, not serum. Overall, 12 of 16 (75%) of these early Lyme disease patients with neurologic involvement had CSF and serum IgM against OspC. Only 3 of 13 (23%) late Lyme disease patients and none of 19 OND controls had CSF IgM directed against OspC. In conclusion, in CSF, OspC and OspA can be coexpressed, and IgM response to them occurs in early Lyme disease patients with neurologic involvement. This biologic finding may also provide a discriminating marker for CNS infection in Lyme disease. PMID:9259573

  9. Serum carbohydrate-binding IgM are present in Vietnamese striped catfish (Pangasianodon hypophthalmus) but not in North African catfish (Clarias gariepinus).

    PubMed

    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.

  10. [Diagnostic value of autoantibodies to MAG by ELISA Bühlmann in 117 immune-mediated peripheral neuropathies associated with monoclonal IgM to SGPG/SGLPG].

    PubMed

    Caudie, C; Kaygisiz, F; Jaquet, P; Petiot, P; Gonnaud, P-M; Antoine, J-C; Vial, C

    2006-01-01

    The neuropathies associated with monoclonal IgM gammopathy reacted with glycoconjugated targets on a very antigenic epitope on the sulfated glucuronic glycolipids corresponding to SGPG and SGLPG (sulfoglucuronyl paragloboside and sulfoglucuronyl lactosaminyl paragloboside), myelin-associated glycoprotein (MAG) and sulfatide. Sometimes monoclonal IgM binds to a broad spectrum of gangliosides. The detection of targets of autoantibodies has considerable importance in the diagnosis and management of patients. It is not known whether the results of antibody tests are equally sensitive and specific for identification of involved auto-antigens. In this study we evaluated the results obtained using IgM reactivity against MAG by enzyme-linked immunosorbent assay (ELISA Bühlmann) with IgM reactivity against SGPG/SGLPG obtained by overlay thin-layer chromatography. We selected 117 patients with anti-SGPG/SGLPG monoclonal gammopathy and peripheral neuropathy and a control group of 102 peripheral neuropathies with 24 having IgM high titres of monoclonal IgM anti-ganglioside antibodies. The anti-MAG sensitivity was 0.97, specificity was 0.86. There is a crossreactivity between 8 (57%) monoclonal IgM antibodies anti-MAG and anti-ganglioside GM1 and 2 (28%) anti-disialylated gangliosides. These results indicate that in clinical practice, anti-MAG ELISA is useful for eliminating anti-MAG neuropathy, as well as for positive diagnosis for titres upper than 10,000 BTU. It is also alpha good test to appreciate clinical improvement after Rituximab treatment.

  11. 2-Hydroxyethyl methacrylate (HEMA) promotes IgG but not IgM antibody production in vivo in mice.

    PubMed

    Andersson, Jennie; Dahlgren, Ulf

    2011-08-01

    Individuals working in a dental clinic are exposed to 2-hydroxyethyl methacrylate (HEMA). HEMA has been found to have several effects on the immune system, including acting as an adjuvant in mice and stimulating the production of human IgG1 in vitro. In this study we continued to explore the immunomodulatory properties of HEMA in mice. Mice were co-injected subcutaneously with the following: HEMA + ovalbumin (OVA) in bicarbonate buffer, OVA in bicarbonate buffer, HEMA in bicarbonate buffer, or bicarbonate buffer alone. Mice immunized with OVA were killed 2 wk after a booster injection. Mice exposed to HEMA only were killed 6 d after the last injection with HEMA. Serum and spleens were collected. The activities of anti-OVA IgG and anti-OVA IgM were determined using ELISAs, as was the in vitro production of tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) by splenocytes after 2 d of incubation. Splenocyte proliferation was analyzed using [(3) H]thymidine decomposition. Mice exposed twice to HEMA in vivo had a higher baseline and a higher concanavalin A-stimulated proliferation of splenocytes, and produced less TNF-α in relation to IL-6, compared with controls. Immunization of mice with OVA/HEMA resulted in a higher anti-OVA IgG activity, relative to anti-OVA IgM activity, compared with controls. In conclusion, HEMA has selective effects on cytokine and antibody production in mice.

  12. Mutations in PIK3CD Can Cause Hyper IgM Syndrome (HIGM) Associated with Increased Cancer Susceptibility

    PubMed Central

    Crank, M. C.; Grossman, J. K.; Moir, S.; Pittaluga, S.; Buckner, C. M.; Kardava, L.; Agharahimi, A.; Meuwissen, H.; Stoddard, J.; Niemela, J.; Kuehn, H.

    2014-01-01

    Autosomal dominant gain of function mutations in the gene encoding PI3K p110δ were recently associated with a novel combined immune deficiency characterized by recurrent sinopulmonary infections, CD4 lymphopenia, reduced class-switched memory B cells, lymphadenopathy, CMV and/or EBV viremia and EBV-related lymphoma. A subset of affected patients also had elevated serum IgM. Here we describe three patients in two families who were diagnosed with HIGM at a young age and were recently found to carry heterozygous mutations in PIK3CD. These patients had an abnormal circulating B cell distribution featuring a preponderance of early transitional (T1) B cells and plasmablasts. When stimulated in vitro, PIK3CD mutated B cells were able to secrete class-switched immunoglobulins. This finding implies that the patients’ elevated serum IgM levels were unlikely a product of an intrinsic B cell functional inability to class switch. All three patients developed malignant lymphoproliferative syndromes that were not associated with EBV. Thus, we identified a novel subset of patients with PIK3CD mutations associated with HIGM, despite indications of preserved in vitro B cell class switch recombination, as well as susceptibility to non-EBV-associated malignancies. PMID:24610295

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

    PubMed Central

    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

  14. Differential diagnosis of IgM MGUS and WM according to B-lymphoid infiltration by morphology and flow cytometry.

    PubMed

    Ocio, Enrique M; del Carpio, Daniel; Caballero, Álvaro; Alonso, Jennifer; Paiva, Bruno; Pesoa, Roberto; Villaescusa, Teresa; López-Anglada, Lucía; Vidriales, Belén; García-Sanz, Ramón

    2011-02-01

    The distinction between IgM monoclonal gammopathy of undetermined significance (MGUS), asymptomatic Waldenstrom's macroglobulinemia (WM; aWM), and symptomatic WM (sWM) relies on two features: the presence of infiltration by lymphoplasmacytic lymphoma in the bone marrow (BM) biopsy and the existence of signs or symptoms attributable to the disease. Nevertheless, some patients lack a BM biopsy or it is not conclusive for diagnosis. In this study we have investigated 94 patients with IgM monoclonal gammopathies, in which a BM trephine biopsy and morphological and flow cytometry (FCM) evaluation of BM aspirate were available at diagnosis. We found a clear correlation between BM infiltration of B-lymphocytes assessed by morphology and by FCM with a Pearson correlation of 0.62 (P<.001). Moreover, in the absence of a BM trephine biopsy, the cut-off points that would help in the differential diagnosis between MGUS, aWM, and sWM would be 20% for morphology and 5% for FCM, both assessed in the BM aspirate.

  15. Validation of IgG, IgM multiplex plasmonic gold platform in French clinical cohorts for the serodiagnosis and follow-up of Toxoplasma gondii infection.

    PubMed

    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.

  16. [IgM antibody detection in acute viral diseases, 1995-2004: analysis of data collected at a commercial diagnostic laboratory in Japan].

    PubMed

    Ban, Fumihiko; Itabashi, Yoshinori; Masui, Yukio; Inouye, Sakae

    2007-07-01

    We analyzed data from tests for virus-specific IgM in 376,000 serum specimens sent to a commercial diagnostic laboratory from clinics nationwide between 1995 and 2004. IgM antibodies to measles, rubella, mumps, parvo B19, and varicella-zoster viruses were tested using IgM-capture ELISA kits. Among specimens, 254,000 (68%) had documentation of age, of which 56% were sera from persons<20 and 44%> or = 20 years of age. Monthly or yearly trends in IgM antibody-positive tests in<20 year-old persons were similar to those in pediatric patients per sentinel clinic reported by the National Epidemiological Surveillance of Infectious Diseases (NESID), which collects weekly numbers of patients with designated infectious diseases from 3000 pediatrics clinics nationwide. Patterns of changes in monthly IgM positive tests in both < 20 and > or = 20 y specimens were similar, indicating that infections occur simultaneously in both children and adults. Adult IgM-positive specimens came from internal medicine clinics and from dermatology clinics for measles; from dermatology and obstetrics clinics for rubella and parvo B19; from otolaryngology clinics for mumps; and from dermatology and otolaryngology clinics for varicella-zoster virus. Analysis of large numbers of IgM test results at regular intervals may contribute to understanding of the epidemiology of these viral diseases in Japan.

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

    PubMed

    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.

  18. Two nephelometric methods compared with a radial immunodiffusion method for the measurement of IgG, IgA and IgM.

    PubMed

    Blanchard, G C; Gardner, R

    1980-04-01

    1. The IgG, IgA and IgM concentrations of a group of 100 or more human sera found by both the rate nephelometric Beckman Immunochemistry System and the endpoint Behring Laser Nephelometer procedure gave good correlations when compared to results obtained by an endpoint radial immunodiffusion method. The correlation coefficients for the Behring method comparisons were 0.958 for IgG, 0.979 for IgA and 0.966 for IgM when only values under 850 IU of IgM/ml were considered. The Beckman system gave correlation coefficients of 0.984 for IgG, 0.993 for IgA and 0.986 for IgM when IgM concentrations were under 500 IU/ml. Determinations from all three methods agreed well except for very high IgM values which were considerably higher by RID. 2. Both nephelometric methods are fast and precise. The average within-run coefficients of variation were 2.6% for the Behring method, 2.2% for the Beckman system and 2.1% for radial immunodiffusion while average between-run precision values of 6.9% for the Behring method, 3.7% for the Beckman system and 4.9% for radial immunodiffusion were found. The Beckman rate system has the advantage of one point calibration, ease of data processing and elimination of sample blanks.

  19. IgM, IgD and IgY and their expression pattern in the Chinese soft-shelled turtle Pelodiscus sinensis.

    PubMed

    Xu, Zhen; Wang, Gai L; Nie, P

    2009-06-01

    Three Ig isotypes, IgM, IgD, and IgA, were previously known in reptiles. Here, in this report we describe IgM, IgD and a novel immunoglobulin heavy-chain isotype upsilon (IgY) in Chinese soft-shelled turtle (Pelodiscus sinensis). The IgM and IgY constant domains are characteristically similar to their counterparts described in other vertebrates. The expression of IgM and IgD were detected at mRNA level early during embryonic development, and their expression increased during further development. However, the IgY expression was not detected in larval turtles until 90 days after hatching-out. The increase in the transcription of these three Ig molecules was analyzed by using real-time PCR in spleen, kidney and blood following the injection of inactivated Aeromonas hydrophila. The primary increase in the expression of these three Igs was observed 1 week after the first injection, although not statistically significant, and the second injection 2 weeks after the first injection provoked a significant increase in the expression of these Igs, revealing a pattern of primary and secondary antibody response in the turtle. The present study represents the first report on reptile IgY and the pattern of IgM, IgD and IgY transcription in reptiles.

  20. [A case of IgM paraproteinemic neuropathy associated with anti-sulfated glucuronic paragloboside (SGPG) IgG antibody without anti-myelin-associated glycoprotein (MAG) activity].

    PubMed

    Nakamura, Haruko; Endo, Masanao; Sugawara, Eriko; Kuwahara, Motoi; Kusunoki, Susumu; Tanaka, Fumiaki; Takahashi, Tatsuya

    2013-01-01

    We report a case of IgM paraproteinemic neuropathy associated with anti-sulfated glucuronic paragloboside (SGPG) IgG antibody. An 84-year old man complained of numbness on the left side of the face and in the distal portions of the limbs. Neurological examination showed mild sensory ataxia. The laboratory tests revealed the presence of IgM lambda paraproteinemia and anti-SGPG IgG antibody without anti-myelin-associated glycoprotein (MAG) activity and anti-MAG/SGPG IgM antibody. Results of nerve conduction study showed decreased sensory nerve action potential (SNAP) amplitude, indicating the presence of sensory-dominant axonal polyneuropathy, and the prolongation of distal latency was not observed. Treatment with corticosteroids resulted in a rapid improvement in neurological abnormalities. In IgM paraproteinemic neuropathy associated with anti-MAG/SGPG antibody, distal acquired demyelinating sensory neuropathy and resistance to immunological treatments are the characteristic pathologic and clinical features, respectively. On the other hand our rare case of IgM paraproteinemic neuropathy positive for anti-SGPG IgG antibody presented with axonal sensory polyneuropathy and a good responsiveness to corticosteroids.

  1. Reduced IgG anti-small nuclear ribonucleoprotein autoantibody production in systemic lupus erythematosus patients with positive IgM anti-cytomegalovirus antibodies

    PubMed Central

    Palafox Sánchez, Claudia Azucena; Satoh, Minoru; Chan, Edward KL; Carcamo, Wendy C; Muñoz Valle, José Francisco; Orozco Barocio, Gerardo; Oregon Romero, Edith; Navarro Hernández, Rosa Elena; Salazar Páramo, Mario; Cabral Castañeda, Antonio; Vázquez del Mercado, Mónica

    2009-01-01

    Introduction Systemic lupus erythematosus is characterized by production of autoantibodies to RNA or DNA–protein complexes such as small nuclear ribonucleoproteins (snRNPs). A role of Epstein–Barr virus in the pathogenesis has been suggested. Similar to Epstein–Barr virus, cytomegalovirus (CMV) infects the majority of individuals at a young age and establishes latency with a potential for reactivation. Homology of CMV glycoprotein B (UL55) with the U1snRNP-70 kDa protein (U1–70 k) has been described; however, the role of CMV infection in production of anti-snRNPs is controversial. We investigated the association of CMV serology and autoantibodies in systemic lupus erythematosus. Methods Sixty-one Mexican patients with systemic lupus erythematosus were tested for CMV and Epstein–Barr virus serology (viral capsid antigen, IgG, IgM) and autoantibodies by immunoprecipitation and ELISA (IgG and IgM class, U1RNP/Sm, U1–70 k, P peptide, rheumatoid factor, dsDNA, β2-glycoprotein I). Results IgG anti-CMV and IgM anti-CMV were positive in 95% (58/61) and 33% (20/61), respectively, and two cases were negative for both. Clinical manifestation and autoantibodies in the IgM anti-CMV(+) group (n = 20) versus the IgM anti-CMV(-)IgG (+) (n = 39) group were compared. Most (19/20) of the IgM anti-CMV(+) cases were IgG anti-CMV(+), consistent with reactivation or reinfection. IgM anti-CMV was unrelated to rheumatoid factor or IgM class autoantibodies and none was positive for IgM anti-Epstein–Barr virus–viral capsid antigen, indicating that this is not simply due to false positive results caused by rheumatoid factor or nonspecific binding by certain IgM. The IgM anti-CMV(+) group has significantly lower levels of IgG anti-U1RNP/Sm and IgG anti-U1–70 k (P = 0.0004 and P = 0.0046, respectively). This finding was also confirmed by immunoprecipitation. Among the IgM anti-CMV(-) subset, anti-Su was associated with anti-U1RNP and anti-Ro (P < 0.05). High levels of Ig

  2. Invariance and restriction toward a limited set of self-antigens characterize neonatal IgM antibody repertoires and prevail in autoreactive repertoires of healthy adults.

    PubMed

    Mouthon, L; Nobrega, A; Nicolas, N; Kaveri, S V; Barreau, C; Coutinho, A; Kazatchkine, M D

    1995-04-25

    Analysis of the reactivity of IgM with self-antigens in tissues by a quantitative immunoblotting technique showed striking invariance among newborns in the human and in the mouse. The self-reactive repertoire of IgM of adults was also markedly conserved; it comprised most anti-self reactivities that prevailed among neonates. Multivariate analysis confirmed the homogeneity of IgM repertoires of neonates toward self- and non-self-antigens. Multivariate analysis discriminated between newborn and adult repertoires for reactivity with two of five sources of self-proteins and with non-self-antigens. Our observations support the concept that naturally activated B lymphocytes are selected early in development and throughout life for reactivity with a restricted set of self-antigens.

  3. Invariance and restriction toward a limited set of self-antigens characterize neonatal IgM antibody repertoires and prevail in autoreactive repertoires of healthy adults.

    PubMed Central

    Mouthon, L; Nobrega, A; Nicolas, N; Kaveri, S V; Barreau, C; Coutinho, A; Kazatchkine, M D

    1995-01-01

    Analysis of the reactivity of IgM with self-antigens in tissues by a quantitative immunoblotting technique showed striking invariance among newborns in the human and in the mouse. The self-reactive repertoire of IgM of adults was also markedly conserved; it comprised most anti-self reactivities that prevailed among neonates. Multivariate analysis confirmed the homogeneity of IgM repertoires of neonates toward self- and non-self-antigens. Multivariate analysis discriminated between newborn and adult repertoires for reactivity with two of five sources of self-proteins and with non-self-antigens. Our observations support the concept that naturally activated B lymphocytes are selected early in development and throughout life for reactivity with a restricted set of self-antigens. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7731992

  4. Severe cranial nerve involvement in a patient with monoclonal anti-MAG/SGPG IgM antibody and localized hard palate amyloidosis.

    PubMed

    Yoshida, Takuhiro; Yazaki, Masahide; Gono, Takahisa; Tazawa, Ko-ichi; Morita, Hiroshi; Matsuda, Masayuki; Funakoshi, Kei; Yuki, Nobuhiro; Ikeda, Shu-ichi

    2006-05-15

    We report a patient with severe cranial polyneuropathy as well as sensory limb neuropathy. Biclonal serum IgM-kappa/IgM-lambda gammopathy was found and serum anti-myelin-associated glycoprotein (MAG)/sulfoglucuronyl paragloboside (SGPG) IgM antibody was also detected. Immunofluorescence analysis of a sural nerve biopsy specimen revealed binding of IgM and lambda-light chain on myelin sheaths. No amyloid deposition was detected in biopsied tissues except for the hard palate, suggesting that the amyloidosis was of the localized type and had no relation to the pathogenesis of cranial neuropathy. Our observations indicate that the anti-MAG/SGPG IgM antibody may be responsible for this patient's cranial polyneuropathy, which is a rare manifestation in anti-MAG/SGPG-associated neuropathy.

  5. Anti-α-glucose-based glycan IgM antibodies predict relapse activity in multiple sclerosis after the first neurological event

    PubMed Central

    Freedman, MS; Laks, J; Dotan, N; Altstock, RT; Dukler, A; Sindic, CJM

    2009-01-01

    Background There is no specific serum-based biomarker for the diagnosis or prognosis of relapsing-remitting multiple sclerosis (RRMS). Objective We investigated whether levels of IgM antibodies to Glc(α1,4)Glc(α) (GAGA4) or to a panel of four glucose-based glycans could differentiate MS from other neurological diseases (OND) or predict risk of early relapse following first presentation (FP) of RRMS. Methods Retrospective analysis of 440 sera samples of three cohorts: A) FP-RRMS (n = 44), OND (n = 44); B) FP-RRMS (n = 167), OND (n = 85); and C) FP (n = 100). Anti-GAGA4 IgM levels were measured by enzyme immunoassay in cohort-A and cohort-B. Cohort-C IgM antibodies to glucosebased glycan panel were measured by immunofluorescence. Results FP-RRMS had higher levels of anti-GAGA4 IgM than OND patients (cohort-A, P = 0.01; cohort-B, P = 0.0001). Sensitivity and specificity were 27% and 97% for cohort-A; and 26% and 90% for cohort-B, respectively. In cohort-C, 58 patients experienced early relapse (<24 months), 31 had late relapse (≥24 months), and 11 did not experience second attack during follow-up. Kaplan– Meier curves demonstrated decrease in time to next relapse for patients positive for the antibody panel (P = 0.02, log rank). Conclusions Serum anti-GAGA4 IgM discerns FP-RRMS patients from OND patients. Higher levels of serum anti-α-glucose IgM in FP patients predict imminent early relapse. PMID:19324980

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

    PubMed Central

    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. PMID:28123554

  7. Differential Modulation of IgT and IgM upon Parasitic, Bacterial, Viral, and Dietary Challenges in a Perciform Fish.

    PubMed

    Piazzon, Maria C; Galindo-Villegas, Jorge; Pereiro, Patricia; Estensoro, Itziar; Calduch-Giner, Josep A; Gómez-Casado, Eduardo; Novoa, Beatriz; Mulero, Victoriano; Sitjà-Bobadilla, Ariadna; Pérez-Sánchez, Jaume

    2016-01-01

    Three different immunoglobulin (Ig) isotypes can be found in teleost fish, IgM, IgD, and the teleost-specific IgT. IgM is considered to have a systemic activity, and IgT is attributed a mucosal role, similar to mammalian IgA. In this study, the complete sequence of gilthead sea bream IgM and IgT in their membrane (m) and soluble (s) forms are described for the first time in a perciform fish. Their constitutive gene expression is analyzed in different tissues, and their regulation upon viral, bacterial, parasitic, mucosal vaccination and dietary challenges are studied. GCB IgM and IgT have the prototypical structure when compared to other fish Igs. The constitutive expression of sIgM was the highest overall in all tissues, whereas mIgT expression was highest in mucosal tissues, such as gills and intestine. IgM and IgT were differentially regulated upon infection. IgT was highly upregulated locally upon infection with the intestinal parasite Enteromyxum leei or systemically after Nodavirus infection. Long-term intestinal parasitic infections increased the serum titer of both isotypes. Mucosal vaccination against Photobacterium damselae subsp. piscicida finely regulated the Ig response inducing a systemic increase of IgM titers in serum and a local IgT response in skin mucus when animals were exposed to the pathogen by bath challenge. Interestingly, plant-based diets inhibit IgT upregulation upon intestinal parasitic challenge, which was related to a worse disease outcome. All these results corroborate the mucosal role of IgT and emphasize the importance of a finely tuned regulation of Ig isotypes upon infection, which could be of special interest in vaccination studies.

  8. The pyloric caeca area is a major site for IgM(+) and IgT(+) B cell recruitment in response to oral vaccination in rainbow trout.

    PubMed

    Ballesteros, Natalia A; Castro, Rosario; Abos, Beatriz; Rodríguez Saint-Jean, Sylvia S; Pérez-Prieto, Sara I; Tafalla, Carolina

    2013-01-01

    Although previous studies have characterized some aspects of the immune response of the teleost gut in response to diverse pathogens or stimuli, most studies have focused on the posterior segments exclusively. However, there are still many details of how teleost intestinal immunity is regulated that remain unsolved, including the location of IgM(+) and IgT(+) B cells along the digestive tract and their role during the course of a local stimulus. Thus, in the current work, we have studied the B cell response in five different segments of the rainbow trout (Oncorhynchus mykiss) digestive tract in both naïve fish and fish orally vaccinated with an alginate-encapsulated DNA vaccine against infectious pancreatic necrosis virus (IPNV). IgM(+) and IgT(+) cells were identified all along the tract with the exception of the stomach in naïve fish. While IgM(+) cells were mostly located in the lamina propria (LP), IgT(+) cells were primarily localized as intraepithelial lymphocytes (IELs). Scattered IgM(+) IELs were only detected in the pyloric caeca. In response to oral vaccination, the pyloric caeca region was the area of the digestive tract in which a major recruitment of B cells was demonstrated through both real time PCR and immunohistochemistry, observing a significant increase in the number of both IgM(+) and IgT(+) IELs. Our findings demonstrate that both IgM(+) and IgT(+) respond to oral stimulation and challenge the paradigm that teleost IELs are exclusively T cells. Unexpectedly, we have also detected B cells in the fat tissue associated to the digestive tract that respond to vaccination, suggesting that these cells surrounded by adipocytes also play a role in mucosal defense.

  9. Multiple Plasmodium falciparum Erythrocyte Membrane Protein 1 Variants per Genome Can Bind IgM via Its Fc Fragment Fcμ

    PubMed Central

    Jeppesen, Anine; Ditlev, Sisse Bolm; Soroka, Vladyslav; Stevenson, Liz; Turner, Louise; Dzikowski, Ron

    2015-01-01

    The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) adhesive proteins expressed on the surfaces of infected erythrocytes (IEs) are of key importance in the pathogenesis of P. falciparum malaria. Several structurally and functionally defined PfEMP1 types have been associated with severe clinical manifestations, such as cerebral malaria in children and placental malaria in pregnant women. PfEMP1 that can bind the Fc part of IgM (Fcμ) characterizes one such type, although the functional significance of this IgM binding to PfEMP1 remains unclear. In this study, we report the identification and functional analysis of five IgM-binding PfEMP1 proteins encoded by P. falciparum NF54. In addition to the VAR2CSA-type PFL0030c protein, already known to bind Fcμ and to mediate chondroitin sulfate A (CSA)-specific adhesion of IEs in the placenta, we found four PfEMP1 proteins not previously known to bind IgM this way. Although they all contained Duffy binding-like ε (DBLε) domains similar to those in VAR2CSA-type PfEMP1, they did not mediate IE adhesion to CSA, and IgM binding did not shield IEs from phagocytosis of IgG-opsonized IEs. In this way, these new IgM-binding PfEMP1 proteins resemble the rosette-mediating and IgM-binding PfEMP1 HB3VAR06, but none of them mediated formation of rosettes. We could map the capacity for Fc-specific IgM binding to DBLε domains near the C terminus for three of the four PfEMP1 proteins tested. Our study provides new evidence regarding Fc-dependent binding of IgM to PfEMP1, which appears to be a common and multifunctional phenotype. PMID:26216422

  10. Evaluation of Commercially Available Diagnostic Tests for the Detection of Dengue Virus NS1 Antigen and Anti-Dengue Virus IgM Antibody

    PubMed Central

    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

  11. Evaluation of commercially available diagnostic tests for the detection of dengue virus NS1 antigen and anti-dengue virus IgM antibody.

    PubMed

    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

    2014-10-01

    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%.

  12. Diagnostic Performance of Five Assays for Anti-Hepatitis E Virus IgG and IgM in a Large Cohort Study

    PubMed Central

    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

  13. Analysis of subsets of B cells, Breg, CD4Treg and CD8Treg cells in adult patients with primary selective IgM deficiency

    PubMed Central

    Louis, Ankmalika Gupta; Agrawal, Sudhanshu; Gupta, Sudhir

    2016-01-01

    Primary selective IgM deficiency (SIGMD) is a rare and recently IUIS-recognized primary immunodeficiency disease with increased susceptibility to infections, allergy, and autoimmune diseases. The pathogenesis of selective IgM remains unclear. The objective of the study was to understand the pathogenesis of selective IgM deficiency via a comprehensive analysis of subsets of B cells, naïve and memory subsets of CD4+ and CD8+ T cells, and Breg, CD4Treg, and CD8Treg cells. Twenty adult patients with SIGMD (serum IgM 4 mg/dl-32 mg/dl) and age-and gender-matched healthy controls were studied. Naïve B cells, transitional B cells, marginal zone B cells, germinal center B cells, IgM memory B cells, switched memory B cells, plasmablasts, CD21low B cells, B1 cells, CXCR3+ naive and memory B cells; naïve, central memory, and effector memory subsets of CD4+ and CD8+ T cells, and CD4Treg, CD8Treg and Breg were phenotypically analyzed using multicolor flow cytometry. A significant increase in CD21low, IgM memory B cells, Breg and CD8Treg, and a significant decreased in germinal center B cells, and CXCR3+ naïve and memory B cells were observed in SIGMD. These alterations in subsets of B cells, and Breg and CD8Treg cells may play a role in the pathogenesis of SIGMD. PMID:27168952

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

    PubMed

    Magez, Stefan; Schwegmann, Anita; Atkinson, Robert; Claes, Filip; Drennan, Michael; De Baetselier, Patrick; Brombacher, Frank

    2008-08-08

    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.

  15. IL-10 production in murine IgM(+) CD138(hi) cells is driven by Blimp-1 and downregulated in class-switched cells.

    PubMed

    Suzuki-Yamazaki, Nao; Yanobu-Takanashi, Rieko; Okamura, Tadashi; Takaki, Satoshi

    2016-12-23

    In contrast to antibody-induced inflammatory responses, some B-cell subpopulations suppress inflammation through the production of interleukin (IL)-10. However, the mechanisms underlying Il10 gene expression during B-cell development is elusive. Here, we identify IgM(+) B220(lo) CD138(hi) cells responsible for marked IL-10 production in the bone marrow and spleen of mice. These murine IL-10-producing cells predominantly secrete IgM and have unique characteristics of long-lived plasma cells in spite of high expression of surface IgM. We found that IL-10 production is strongly correlated with the expression level of Prdm1 (encoding the Blimp-1 protein), an essential regulator of plasma cell development. Furthermore, overexpression of Prdm1 induces Il10 expression in naïve B cells. Immunoglobulin class-switching recombination events resulted in the downregulation of both Il10 and Prdm1 expression in differentiating B cells. Thus, the prolonged elevation of Blimp-1 expression during the formation of IgM(+) CD138(hi) cells without class-switching elicits IL-10 production. Adoptive transfer of Il10-deficient B cells into B-cell-deficient mice demonstrated that IgM(+) CD138(hi) cell-derived IL-10 supports the survival of class-switched plasma cells and their antibody production in response to antigen challenge. These findings reveal an important role for IL-10 secretion by IgM(+) CD138(hi) cells in the complete and efficient humoral response.

  16. Differential Modulation of IgT and IgM upon Parasitic, Bacterial, Viral, and Dietary Challenges in a Perciform Fish

    PubMed Central

    Piazzon, Maria C.; Galindo-Villegas, Jorge; Pereiro, Patricia; Estensoro, Itziar; Calduch-Giner, Josep A.; Gómez-Casado, Eduardo; Novoa, Beatriz; Mulero, Victoriano; Sitjà-Bobadilla, Ariadna; Pérez-Sánchez, Jaume

    2016-01-01

    Three different immunoglobulin (Ig) isotypes can be found in teleost fish, IgM, IgD, and the teleost-specific IgT. IgM is considered to have a systemic activity, and IgT is attributed a mucosal role, similar to mammalian IgA. In this study, the complete sequence of gilthead sea bream IgM and IgT in their membrane (m) and soluble (s) forms are described for the first time in a perciform fish. Their constitutive gene expression is analyzed in different tissues, and their regulation upon viral, bacterial, parasitic, mucosal vaccination and dietary challenges are studied. GCB IgM and IgT have the prototypical structure when compared to other fish Igs. The constitutive expression of sIgM was the highest overall in all tissues, whereas mIgT expression was highest in mucosal tissues, such as gills and intestine. IgM and IgT were differentially regulated upon infection. IgT was highly upregulated locally upon infection with the intestinal parasite Enteromyxum leei or systemically after Nodavirus infection. Long-term intestinal parasitic infections increased the serum titer of both isotypes. Mucosal vaccination against Photobacterium damselae subsp. piscicida finely regulated the Ig response inducing a systemic increase of IgM titers in serum and a local IgT response in skin mucus when animals were exposed to the pathogen by bath challenge. Interestingly, plant-based diets inhibit IgT upregulation upon intestinal parasitic challenge, which was related to a worse disease outcome. All these results corroborate the mucosal role of IgT and emphasize the importance of a finely tuned regulation of Ig isotypes upon infection, which could be of special interest in vaccination studies. PMID:28082977

  17. Serological Diagnosis of Acute Scrub Typhus in Southern India: Evaluation of InBios Scrub Typhus Detect IgM Rapid Test and Comparison with other Serological Tests

    PubMed Central

    Anitharaj, Velmurugan; Pradeep, Jothimani; Park, Sungman; Kim, Seung-Han; Kim, Young Jin; Kim, Eun-Ye; Kim, Yoon-Won

    2016-01-01

    Introduction 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. Aim 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. Materials and Methods 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). Results 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. Conclusion 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. PMID:28050364

  18. [Determination of immunoglobulins IgG, IgM and IgA in maternal serum in patients with intrauterine growth retardation].

    PubMed

    Möller, U; Seewald, H J; Groh, A; Ader, B

    1987-01-01

    Immunoglobulin IgG, IgM, and IgA were analysed in maternal serum of 33 patients with intrauterine growth retardation and 30 patients without hypotrophic newborns. The estimations of the immunoglobulins were carried out by means of single radial immunodiffusion according to Mancini and coworkers. There were no significant differences between both groups of patients. Therefore IgG, IgM, and IgA are no additional parameters for estimation of the placental function of the 3rd trimester of pregnancy.

  19. Detection of MYD88 L265P in peripheral blood of patients with Waldenström's Macroglobulinemia and IgM monoclonal gammopathy of undetermined significance.

    PubMed

    Xu, L; Hunter, Z R; Yang, G; Cao, Y; Liu, X; Manning, R; Tripsas, C; Chen, J; Patterson, C J; Kluk, M; Kanan, S; Castillo, J; Lindeman, N; Treon, S P

    2014-08-01

    MYD88 L265P is highly prevalent in Waldenstrom's Macroglobulinemia (WM) and IgM monoclonal gammopathy of unknown significance (MGUS). We investigated whether MYD88 L265P could be identified by peripheral blood (PB) allele-specific PCR. MYD88 L265P was detected in untreated WM (114/118; 96.6%); previously treated WM (63/102; 61.8%); and IgM MGUS (5/12; 41.7%) but in none of 3 hyper-IgM or 40 healthy individuals. Median PB MYD88 L265P ΔCt was 3.77, 7.24, 10.89, 12.33 and 14.07 for untreated WM, previously treated WM, IgM MGUS, hyper-IgM and healthy individuals, respectively (P<0.0001). For the 232 IgM MGUS and WM patients, PB MYD88 L265P ΔCt moderately correlated to bone marrow (BM) disease (r=-0.3553; P<0.0001), serum IgM (r=-0.3262; P<0.0001) and hemoglobin (r=0.3005; P<0.0001) levels. PB MYD88 L265P ΔCt and serum IgM correlated similarly with BM disease burden. For positive patients, PB MYD88 L265P ΔCt was <6.5 in 100/114 (88%) untreated WM, and >6.5 in 4/5 (80%) IgM MGUS patients (P=0.0034). Attainment of a negative PB MYD88 L265P mutation status was associated with lower BM disease (P=0.001), serum IgM (P=0.019) and higher hemoglobin (P=0.004) levels in treated patients. These studies show the feasibility for detecting MYD88 L265P by PB examination, and the potential for PB MYD88 L265P ΔCt use in the diagnosis and management of WM patients.

  20. Motor-dominant polyneuropathy due to IgM monoclonal antibody against disialosyl gangliosides in a patient with mantle cell lymphoma.

    PubMed

    Mori, Akio; Ueno, Yuji; Kuroki, Takuma; Hoshino, Yasunobu; Shimura, Hideki; Sekiguchi, Yasunobu; Noguchi, Masaaki; Hamada, Yukihiro; Kusunoki, Susumu; Hattori, Nobutaka; Urabe, Takao

    2014-02-15

    A rapidly progressive motor-dominant neuropathy associated with IgM monoclonal antibody against gangliosides with disialosyl residues, GD3, GD1b, GT1b, and GQ1b, in a 60-year-old Japanese man with mantle cell lymphoma is reported. Plasma exchange and chemotherapy for mantle cell lymphoma were performed for the neuropathy and mantle cell lymphoma. After therapy, the motor neuropathy dramatically improved concurrently with substantial reduction of the antibody activities especially in reaction to GD1b. This is the first case report of neuropathy with anti-disialosyl IgM antibodies associated with mantle cell lymphoma, and plasma exchange and chemotherapy were effective.

  1. IgM antibodies to N-acetylgalactosaminyl GD1a in benign monomelic amyotrophy of the lower limb.

    PubMed

    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.

  2. Generation of Human Antigen-Specific Monoclonal IgM Antibodies Using Vaccinated “Human Immune System” Mice

    PubMed Central

    van Geelen, Caroline M. M.; Noerder, Miriam; Huntington, Nicholas D.; Lim, Annick; Yasuda, Etsuko; Diehl, Sean A.; Scheeren, Ferenc A.; Ott, Michael; Weijer, Kees; Wedemeyer, Heiner; Di Santo, James P.; Beaumont, Tim; Guzman, Carlos A.; Spits, Hergen

    2010-01-01

    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. PMID:20957227

  3. Measuring Alignments between Galaxies and the Cosmic Web at z ∼ 2–3 Using IGM Tomography

    NASA Astrophysics Data System (ADS)

    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 }}< \\cos θ > , 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 }}< \\cos θ > ∼ 0.1, but much larger surveys encompassing >10,000 galaxies, such as Subaru PFS, will be required to constrain models with {{Δ }}< \\cos θ > ∼ 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.

  4. Development and evaluation of a Sarcocystis neurona-specific IgM capture enzyme-linked immunosorbent assay.

    PubMed

    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 < .0001). For horses inoculated with lower doses of S 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.

  5. In vitro molecular evolution of AL NEIBMs improved immunoglobulin (Ig) binding and antibody detection.

    PubMed

    He, Ting; Ding, Ying-Ying; Feng, Jiao-Jiao; Chen, Qiu-Li; Zhu, Huai-Min; Peng, Heng; Rui, Bing; Li, Xiang-Yu; Cao, Ming-Mei; Pan, Wei

    2014-08-20

    AL (SpA A domain-PpL B3 domain), LD5 (PpL B3 domain-SpA D domain-PpL B3 domain-SpA D domain-PpL B3 domain, L-D-L-D-L) and LD3 (PpL B3 domain-SpA D domain-PpL B3 domain, L-D-L) are novel evolved Ig binding molecules (NEIBMs) derived from the in vitro molecular evolution of combinatorial phage libraries displaying randomly rearranged Ig-binding domains of protein A and protein L. These molecules all showed novel Ig-binding properties of double-site binding to the VH3 and Vκ regions of human Ig Fab and high affinity for human IgM, which enhanced IgM detection in the anti-HCV ELISA assay. In this double-site binding, the A domain binds to the VH3 chain with low affinity. Whether the appropriate mutations in the A domain could improve this binding remains unknown. In this study, four combinatorial phage libraries displaying AL mutants with random mutations at different amino acid positions in the A domain were constructed. Seven AL mutant phages with significantly improved Ig binding activity were obtained from the phage library displaying AL mutants randomly mutated at positions 27 and 34 through human IgM-directed in vitro evolution. Two of the seven prokaryotically expressed AL mutants, AL (VV) and AL (KA), exhibited IgM and IgG binding activities equivalent to those of wild-type AL, whereas other mutants showed attenuated binding. However, after labeling with HRP, AL (VV) and AL (KA) showed improved IgM and IgG binding activity, which significantly improved the detection in the anti-HCV assay. Thus, the present study demonstrates that the binding properties of AL were successfully improved through phage-based molecular evolution, which could substantially contribute to the use of AL in antibody detection, and provides an example of successful protein engineering through in vitro molecular evolution.

  6. Search for QSOS Suitable for Subsequent Observation of he II 304 Absorption Arising in the IGM, Ly-Alpha and ... PART3

    NASA Astrophysics Data System (ADS)

    Tytler, David

    1991-07-01

    THIS IS PART Three OF PROPOSAL 3801. IT CONTAINS 40 TARGETS OF HIGH PRIORITY. EXCEPT FOR TARGETS, THIS PROPOSAL IS IDENTICAL TO 3801. Targets are in order of decreasing priority. Priority matters a lot. Best targets are listed first. Ultraviolet images will be obtained in snapshot mode of the 500 known high-redshift (z > 2.8) QSOs in order to identify the few (about 20) targets which have sufficient ultraviolet flux for subsequent FOC/FOS or GHRS observations of He II 304. The detection of absorption by the Helium II Lyman-alpha line at 304 A, one of the most exciting prospects of the HST, will provide the first direct detection of the diffuse intergalactic medium (IGM). The absence of Gunn-Peterson H I 1215 absorption shows that the IGM is hot and/or of very low density, thus He I 584 is not expected to be observable. He II 304--the most promising line--should be observable from three sources: the diffuse IGM, the discrete Ly-alpha clouds, and the much rarer metal line absorption systems. The Gunn-Peterson continuum optical depth is not well constrained by models (range 0.3-3000). The mere detection of only one QSO below 304 A would rule out many models, limiting the IGM density, temperature, and ionization mechanisms. Similarly the total absence of flux from several targets would rule out other models.

  7. Search for QSOS Suitable for Subsequent Observation of he II 304 Absorption Arising in the IGM, Ly-Alpha and ... PART2

    NASA Astrophysics Data System (ADS)

    Tytler, David

    1991-07-01

    THIS IS PART TWO OF PROPOSAL 3801, CONTAINING 55 TARGETS OF PRIORITY 7,8 AND 9. EXCEPT FOR TARGETS, THIS PROPOSAL IS IDENTICAL TO 3801, WHICH HAS 87 TARGETS OF PRIORITY 3,4,5 AND 6. Ultraviolet images will be obtained in snapshot mode of the 500 known high-redshift (z > 2.8) QSOs in order to identify the few (about 20) targets which have sufficient ultraviolet flux for subsequent FOC/FOS or GHRS observations of He II 304. The detection of absorption by the Helium II Lyman-alpha line at 304 A, one of the most exciting prospects of the HST, will provide the first direct detection of the diffuse intergalactic medium (IGM). The absence of Gunn-Peterson H I 1215 absorption shows that the IGM is hot and/or of very low density, thus He I 584 is not expected to be observable. He II 304--the most promising line--should be observable from three sources: the diffuse IGM, the discrete Ly-alpha clouds, and the much rarer metal line absorption systems. The Gunn-Peterson continuum optical depth is not well constrained by models (range 0.3-3000). The mere detection of only one QSO below 304 A would rule out many models, limiting the IGM density, temperature, and ionization mechanisms. Similarly the total absence of flux from several targets would rule out other models.

  8. Immune dysfunction in Rett syndrome patients revealed by high levels of serum anti-N(Glc) IgM antibody fraction.

    PubMed

    Papini, Anna Maria; Nuti, Francesca; Real-Fernandez, Feliciana; Rossi, Giada; Tiberi, Caterina; Sabatino, Giuseppina; Pandey, Shashank; Leoncini, Silvia; Signorini, Cinzia; Pecorelli, Alessandra; Guerranti, Roberto; Lavielle, Solange; Ciccoli, Lucia; Rovero, Paolo; De Felice, Claudio; Hayek, Joussef

    2014-01-01

    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.

  9. IgM, IgA and IgG producing cells in cerebrospinal fluid and peripheral blood in multiple sclerosis.

    PubMed Central

    Henriksson, A; Kam-Hansen, S; Link, H

    1985-01-01

    The protein A plaque assay was used to enumerate IgM, IgA and IgG producing cells per 20 X 10(3) lymphocytes in cerebrospinal fluid (CSF) and peripheral blood (PB) from 37 patients with multiple sclerosis (MS) and in PB from healthy controls. Fifty-seven percent of the MS patients displayed in CSF cells producing IgM, 70% IgA and 89% IgG. IgM or IgA producing cells predominated in CSF from 10 patients, IgG in 27. Immunoglobulin producing cells were often present when the corresponding CSF Ig index was normal, confirming that enumeration of Ig producing cells is a more sensitive variable of the intrathecal immune status. No Ig producing cells were found in CSF from four patients with tension headache, indicating absence of intrathecal Ig synthesis in healthy individuals. The patients with MS had higher numbers of IgM, IgA and IgG producing cells in PB than healthy controls, confirming occurrence of an extrathecal B cell response in MS. Active and stable MS patients did not differ regarding Ig producing cells in CSF nor in PB, which speaks in favour of continuous immune activity within as well as outside the CNS independent of clinical symptoms. PMID:4064372

  10. Immune Dysfunction in Rett Syndrome Patients Revealed by High Levels of Serum Anti-N(Glc) IgM Antibody Fraction

    PubMed Central

    Papini, Anna Maria; Real-Fernandez, Feliciana; Rossi, Giada; Tiberi, Caterina; Sabatino, Giuseppina; Pandey, Shashank; Lavielle, Solange; Ciccoli, Lucia; Hayek, Joussef

    2014-01-01

    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. PMID:25389532

  11. Distinct Differentiation Programs Triggered by IL-6 and LPS in Teleost IgM+ B Cells in The Absence of Germinal Centers

    PubMed Central

    Abós, Beatriz; Wang, Tiehui; Castro, Rosario; Granja, Aitor G.; Leal, Esther; Havixbeck, Jeffrey; Luque, Alfonso; Barreda, Daniel R.; Secombes, Chris J.; Tafalla, Carolina

    2016-01-01

    Although originally identified as a B cell differentiation factor, it is now known that mammalian interleukin-6 (IL-6) only regulates B cells committed to plasma cells in response to T-dependent (TD) antigens within germinal centers (GCs). Even though adaptive immunity is present in teleost fish, these species lack lymph nodes and GCs. Thus, the aim of the present study was to establish the role of trout IL-6 on B cells, comparing its effects to those induced by bacterial lipopolysaccharide (LPS). We demonstrate that the effects of teleost IL-6 on naïve spleen B cells include proliferation, activation of NF-κB, increased IgM secretion, up-regulation of Blimp1 transcription and decreased MHC-II surface expression that point to trout IL-6 as a differentiation factor for IgM antibody-secreting cells (ASCs). However, LPS induced the secretion of IgM without up-regulating Blimp1, driving the cells towards an intermediate activation state in which antigen presenting mechanisms are elicited together with antibody secretion and expression of pro-inflammatory genes. Our results reveal that, in trout, IL-6 is a differentiation factor for B cells, stimulating IgM responses in the absence of follicular structures, and suggest that it was after follicular structures appeared that this cytokine evolved to modulate TD responses within the GC. PMID:27481356

  12. Agglutinating mouse IgG3 compares favourably with IgMs in typing of the blood group B antigen: Functionality and stability studies

    PubMed Central

    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

  13. Immunohistochemical detection of IgM and IgG in lung tissue of dogs with leptospiral pulmonary haemorrhage syndrome (LPHS)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Leptospiral pulmonary haemorrhage syndrome (LPHS) is a severe form of leptospirosis. Pathogenic mechanisms are poorly understood. Lung tissues from 26 dogs with LPHS, 5 dogs with pulmonary haemorrhage due to other causes and 6 healthy lungs were labelled for IgG, IgM and leptospiral antigens. Three ...

  14. Agglutinating mouse IgG3 compares favourably with IgMs in typing of the blood group B antigen: Functionality and stability studies.

    PubMed

    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.

  15. Multiplex Detection of IgG and IgM to Rift Valley Fever Virus Nucleoprotein, Nonstructural Proteins, and Glycoprotein in Ovine and Bovine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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. Evaluation of fully automated assays for the detection of Rubella IgM and IgG antibodies by the Elecsys(®) immunoassay system.

    PubMed

    van Helden, Josef; Grangeot-Keros, Liliane; Vauloup-Fellous, Christelle; Vleminckx, Renaud; Masset, Frédéric; Revello, Maria-Grazia

    2014-04-01

    Screening for acute rubella infection in pregnancy is an important element of antenatal care. This study compared the sensitivity, specificity and reproducibility of two new, fully automated Elecsys(®) Rubella IgM and IgG immunoassays designed for the Elecsys 2010, Modular Analytics E170, COBAS e-411 and COBAS e-601 and e602 analytical platforms, with current assays using serum from patients with primary rubella infections, vaccinated patients, patients with potentially cross-reacting infections and on routine samples in clinical laboratories in France, Germany and Italy. Both assays showed good within-run and within-laboratory precision. A sensitivity of 79.8-96.0% was demonstrated for Elecsys IgM in primary, early acute infection, consistent with existing assays. In samples obtained from routine antenatal screening, the Elecsys Rubella IgM assay revealed high specificity (98.7-99.0%). A significantly (p<0.0001) lower reactivity was demonstrated in samples from previously infected patients where acute rubella infection was excluded, and the incidence of false positives in patients with potentially cross-reacting infections was lower with Elecsys Rubella IgM compared with other. The Elecsys Rubella IgG assay exhibited a relative sensitivity of 99.9-100.0% and specificity of 97.4-100.0% in samples from routine antenatal screening. The Elecsys Rubella IgM and IgG assays allow convenient, rapid and reliable determination of anti-rubella antibodies. Sensitivity, specificity and reproducibility were comparable with existing assay systems. Assay results were available in approximately half the time required for currently employed methods and the assays are compatible with widely used analytical platforms.

  17. Utility of IgM ELISA, TaqMan real-time PCR, reverse transcription PCR, and RT-LAMP assay for the diagnosis of Chikungunya fever.

    PubMed

    Reddy, Vijayalakshmi; Ravi, Vasanthapuram; Desai, Anita; Parida, Manmohan; Powers, Ann M; Johnson, Barbara W

    2012-11-01

    Chikungunya fever a re-emerging infection with expanding geographical boundaries, can mimic symptoms of other infections like dengue, malaria which makes the definitive diagnosis of the infection important. The present study compares the utility of four laboratory diagnostic methods viz. IgM capture ELISA, an in house reverse transcription PCR for the diagnosis of Chikungunya fever, TaqMan real-time PCR, and a one step reverse transcription-loop mediated isothermal amplification assay (RT-LAMP). Out of the 70 serum samples tested, 29 (41%) were positive for Chikungunya IgM antibody by ELISA and 50 (71%) samples were positive by one of the three molecular assays. CHIKV specific nucleic acid was detected in 33/70 (47%) by reverse transcription PCR, 46/70 (66%) by TaqMan real-time PCR, and 43/70 (62%) by RT-LAMP assay. A majority of the samples (62/70; 89%) were positive by at least one of the four assays used in the study. The molecular assays were more sensitive for diagnosis in the early stages of illness (2-5 days post onset) when antibodies were not detectable. In the later stages of illness, the IgM ELISA is a more sensitive diagnostic test. In conclusion we recommend that the IgM ELISA be used as an initial screening test followed one of the molecular assays in samples that are collected in the early phase of illness and negative for CHIKV IgM antibodies. Such as approach would enable rapid confirmation of the diagnosis and implementation of public health measures especially during outbreaks.

  18. In Vivo-Expressed Proteins of Virulent Leptospira interrogans Serovar Autumnalis N2 Elicit Strong IgM Responses of Value in Conclusive Diagnosis

    PubMed Central

    Raja, Veerapandian; Shanmughapriya, Santhanam; Kanagavel, Murugesan; Artiushin, Sergey C.; Velineni, Sridhar; Timoney, John F.

    2015-01-01

    Leptospirosis is a serious zoonosis that is underdiagnosed because of limited access to laboratory facilities in Southeast Asia, Central and South America, and Oceania. Timely diagnosis of locally distributed serovars of high virulence is crucial for successful care and outbreak management. Using pooled patient sera, an expression gene library of a virulent Leptospira interrogans serovar Autumnalis strain N2 isolated in South India was screened. The identified genes were characterized, and the purified recombinant proteins were used as antigens in IgM enzyme-linked immunosorbent assay (ELISA) either singly or in combination. Sera (n = 118) from cases of acute leptospirosis along with sera (n = 58) from healthy subjects were tested for reactivity with the identified proteins in an ELISA designed to detect specific IgM responses. We have identified nine immunoreactive proteins, ArgC, RecA, GlpF, FliD, TrmD, RplS, RnhB, Lp28.6, and Lrr44.9, which were found to be highly conserved among pathogenic leptospires. Apparently, the proteins ArgC, RecA, GlpF, FliD, TrmD, and Lrr44.9 are expressed during natural infection of the host and undetectable in in vitro cultures. Among all the recombinant proteins used as antigens in IgM ELISA, ArgC had the highest sensitivity and specificity, 89.8% and 95.5%, respectively, for the conclusive diagnosis of leptospirosis. The use of ArgC and RecA in combination for IgM ELISA increased the sensitivity and specificity to 95.7% and 94.9%, respectively. ArgC and RecA thus elicited specific IgM responses and were therefore effective in laboratory confirmation of Leptospira infection. PMID:26607308

  19. Development and evaluation of indirect ELISAs for the detection of IgG, IgM and IgA1 against duck hepatitis A virus 1.

    PubMed

    Mao, Sai; Ou, XuMin; Zhu, DeKang; Chen, Shun; Ma, GuangPeng; Wang, MingShu; Jia, RenYong; Liu, MaFeng; Sun, KunFeng; Yang, Qiao; Wu, Ying; Chen, XiaoYue; Cheng, AnChun

    2016-11-01

    Duck hepatitis A virus 1 (DHAV-1) is the principal pathogen that causes duck viral hepatitis (DHV), a highly fatal infectious disease in ducklings. Given the importance of the humoral immune response in the clearance of DHAV-1, indirect enzyme-linked immunosorbent assays (I-ELISAs) to detect immune indices, including IgG, IgM and IgA1, were developed and evaluated in this study. The optimal concentrations of coating-antigen were 1.79μg/ml, 2.23μg/ml and 2.23μg/ml for IgG, IgM and IgA1, respectively. Meanwhile, the optimal dilutions of sera were 1:80, 1:40 and 1:40, respectively; and of the conjugates were 1:300, 1:1800 and 1:800, respectively. Based on these conditions, three linear regression equations, y=1.363+1.954x (r(2)=0.983), y=1.141+2.228x (r(2)=0.970) and y=1.103+1.559x (r(2)=0.995) were derived for IgG, IgM and IgA1, respectively. Analytical sensitivities of the new methods were 1:2560, 1:1280 and 1:640 for IgG, IgM and IgA1, respectively. The concordances between the I-ELISAs and serum-neutralization were 95.2% for IgG and IgA1, and 75% for IgM. Although there was a weak cross-reaction with DHAV-3 positive serum for the IgG and IgA1 tests, it didn't affect the ability to detect DHAV-1 specific antibodies. Thus, these new I-ELISAs were shown to be potentially convenient methods to survey the status of humoral immune response to DHAV-1.

  20. IgG avidity assay: a tool for excluding acute toxoplasmosis in prolonged IgM titer sera from pregnant women.

    PubMed

    Emelia, O; Rahana, A R; Mohamad Firdaus, A; Cheng, H S; Nursyairah, M S; Fatinah, A S; Azmawati, M N; Siti, N A M; Aisah, M Y

    2014-12-01

    An accurate diagnosis for toxoplasmosis is crucial for pregnant women as this infection may lead to severe sequelae in the fetus. The value of IgG avidity assay as a tool to determine acute and chronic toxoplasmosis during pregnancy was evaluated in Universiti Kebangsaan Malaysia Medical Centre (UKMMC). In this study, 281 serum samples from 281 pregnant women in various trimesters were collected. These samples were assayed using specific anti-Toxoplasma IgM and IgG antibodies, followed by IgG avidity test. The overall seroprevalence of toxoplasmosis in pregnant women was 35.2% (33.5% for anti-Toxoplasma IgG and 1.8% for both anti-Toxoplasma IgG and IgM antibodies). Of 5 (1.8%) serum samples positive for IgM ELISA, 4 had high-avidity antibodies, suggesting past infection and one sample with borderline avidity index. Two samples with low avidity were from IgM negative serum samples. The IgG avidity assay exhibited an excellent specificity of 97.6% and a negative predictive value (NPV) of 95.6%. The study also demonstrated no significant correlation between avidity indexes of the sera with IgG (r=0.12, p=0.24) and IgM (r=-0.00, p=0.98), suggesting the complementary needs of the two tests for a better diagnosis outcome. These findings highlight the usefulness of IgG avidity assay in excluding a recently acquired toxoplasmosis infection in IgM-positive serum sample.

  1. Pre-cut Filter Paper for Detecting Anti-Japanese Encephalitis Virus IgM from Dried Cerebrospinal Fluid Spots

    PubMed Central

    Bharucha, Tehmina; Chanthongthip, Anisone; Phuangpanom, Soumphou; Phonemixay, Ooyanong; Sengvilaipaseuth, Onanong; Vongsouvath, Manivanh; Lee, Sue; Newton, Paul N.; Dubot-Pérès, Audrey

    2016-01-01

    Background The use of filter paper as a simple, inexpensive tool for storage and transportation of blood, ‘Dried Blood Spots’ or Guthrie cards, for diagnostic assays is well-established. In contrast, there are a paucity of diagnostic evaluations of dried cerebrospinal fluid (CSF) spots. These have potential applications in low-resource settings, such as Laos, where laboratory facilities for central nervous system (CNS) diagnostics are only available in Vientiane. In Laos, a major cause of CNS infection is Japanese encephalitis virus (JEV). We aimed to develop a dried CSF spot protocol and to evaluate its diagnostic performance using the World Health Organisation recommended anti-JEV IgM antibody capture enzyme-linked immunosorbent assay (JEV MAC-ELISA). Methodology and Principal Findings Sample volumes, spotting techniques and filter paper type were evaluated using a CSF-substitute of anti-JEV IgM positive serum diluted in Phosphate Buffer Solution (PBS) to end-limits of detection by JEV MAC-ELISA. A conventional protocol, involving eluting one paper punch in 200μl PBS, did not detect the end-dilution, nor did multiple punches utilising diverse spotting techniques. However, pre-cut filter paper enabled saturation with five times the volume of CSF-substitute, sufficiently improving sensitivity to detect the end-dilution. The diagnostic accuracy of this optimised protocol was compared with routine, neat CSF in a pilot, retrospective study of JEV MAC-ELISA on consecutive CSF samples, collected 2009–15, from three Lao hospitals. In comparison to neat CSF, 132 CSF samples stored as dried CSF spots for one month at 25–30°C showed 81.6% (65.7–92.3 95%CI) positive agreement, 96.8% (91.0–99.3 95%CI) negative agreement, with a kappa coefficient of 0.81 (0.70–0.92 95%CI). Conclusions/Significance The novel design of pre-cut filter paper saturated with CSF could provide a useful tool for JEV diagnostics in settings with limited laboratory access. It has the

  2. Polymerization of secretory IgM in B lymphocytes is prevented by a prior targeting to a degradation pathway.

    PubMed

    Shachar, I; Amitay, R; Rabinovich, E; Haimovich, J; Bar-Nun, S

    1992-12-05

    B lymphocytes express on their surface a membrane form of IgM (mIgM), and synthesize but fail to secrete a secretory form of IgM (sIgM). Plasma cells shift to the exclusive synthesis and efficient secretion of sIgM. The sIgM in B cells differs from that in plasma cells in its pattern of assembly: in plasma cells, monomers of sIgM are assembled into polymers and only polymers are secreted; in B lymphocytes, monomeric sIgM is neither polymerized nor secreted and is degraded intracellularly. In this article we blocked the export of proteins from the endoplasmic reticulum at low temperatures or with energy poisons or brefeldin A, and localized the different assembly steps of mIgM and sIgM in the 38C B lymphocytes and of sIgM in the 38C-derived sIgM-secreting D2 hybridoma. In both cell lines, sIgM assembly into monomers was not affected, whereas polymerization of sIgM in D2 cells and monomer formation of mIgM in 38C cells were strongly inhibited. Moreover, probing with specific lectins revealed galactosylated monomers and polymers in D2 cells and galactosylated hemimer and monomers only of mIgM in 38C cells. In addition, when Golgi functions were hampered with Tris base, monomerization of mIgM and polymerization of sIgM were attenuated. These results indicate that polymerization of sIgM in D2 cells and monomerization of mIgM in 38C cells are post-endoplasmic reticulum events, occurring in or beyond the trans-Golgi galactosylation compartment. Since only polymers are secreted from D2 cells and only monomeric mIgM is displayed on the surface of 38C cells, partially assembled molecules may traverse the secretory pathway yet are restricted from the cell surface. Furthermore, monomeric sIgM in 38C cells is never galactosylated, thus it is degraded prior to the galactosylation compartment. We conclude that targeting of sIgM to degradation in 38C cells precedes its assembly site into polymers in D2 cells. This implies that degradation of sIgM does not result from the

  3. Low Levels of IgM Antibodies against an Advanced Glycation Endproduct-Modified Apolipoprotein B100 Peptide Predict Cardiovascular Events in Nondiabetic Subjects.

    PubMed

    Engelbertsen, Daniel; Vallejo, Jenifer; Quách, Tâm Dan; Fredrikson, Gunilla Nordin; Alm, Ragnar; Hedblad, Bo; Björkbacka, Harry; Rothstein, Thomas L; Nilsson, Jan; Bengtsson, Eva

    2015-10-01

    Increased glucose levels are associated with the generation of advanced glycation endproduct (AGE) modifications. Interaction between AGE-modified plaque components and immune cells is believed to have an important role in the development of vascular complications in diabetes. Methylglyoxal (MGO) is one type of reactive aldehyde that gives rise to AGE modification. The present study analyzed whether autoantibodies against MGO-modified epitopes of the low-density lipoprotein apolipoprotein B (apoB) 100 predict cardiovascular events. A library consisting of 302 peptides comprising the complete apoB100 molecule was screened to identify peptides targeted by MGO-specific autoantibodies. Peptide (p) 220 (apoB amino acids 3286-3305) was identified as a major target. Baseline IgM and IgG against MGO-peptide 220 (p220) were measured in 700 individuals from the Malmö Diet and Cancer Cohort. A total of 139 cardiovascular events were registered during the 15-y follow-up period. Controlling for major cardiovascular risk factors demonstrated that subjects in the lowest tertile of MGO-p220 IgM had an increased risk for cardiovascular events (hazard ratio [95% confidence interval]: 2.07 [1.22-3.50]; p(trend) = 0.004). Interestingly, the association between MGO-p220 IgM and cardiovascular events remained and even tended to become stronger when subjects with prevalent diabetes were excluded from the analysis (2.51 [1.37-4.61]; p(trend) = 0.002). MGO-p220 IgM was inversely associated with blood glucose, but not with oxidized low-density lipoprotein. Finally, we demonstrate that anti-MGO-p220 IgM is produced by B1 cells. These data show that subjects with low levels of IgM recognizing MGO-modified p220 in apoB have an increased risk to develop cardiovascular events and that this association is present in nondiabetic subjects.

  4. Zebrafish immunoglobulin IgD: unusual exon usage and quantitative expression profiles with IgM and IgZ/T heavy chain isotypes.

    PubMed

    Zimmerman, Anastasia M; Moustafa, Farah M; Romanowski, Kryzstof E; Steiner, Lisa A

    2011-09-01

    The zebrafish is an emerging model for comparative immunology and biomedical research. In contrast to the five heavy chain isotype system of mice and human (IgD, IgM, IgA, IgG, IgE), zebrafish harbor gene segments for IgD, IgM, and novel heavy chain isotype called IgZ/T which appears restricted to bony fishes. The purpose of this study was to design and validate a suite of quantitative real time RT-PCR protocols to measure IgH expression in a vertebrate model which has considerable promise for modeling both pathogenic infection and chronic conditions leading to immune dysfunction. Specific primers were designed and following verification of their specificty, relative expression levels of IgD, IgM, and IgZ/T were measured in triplicate for zebrafish raised under standard laboratory conditions. During embryonic stages, low levels of each heavy chain isotype (IgH) were detected with each increasing steadily between 2 and 17 weeks post fertilization. Overall IgM>IgZ>IgD throughout zebrafish development with the copy number of IgM being several fold higher than that of IgD or IgZ/T. IgD exon usage was also characterized, as its extremely long size and presence of a stop codon in the second IgD exon in zebrafish, raised questions as to how this antibody might be expressed. Zebrafish IgD was found to be a chimeric immunoglobulin, with the third IgD exon spliced to the first IgM constant exon thereby circumventing the first and second IgD exons. Collectively, the qRT-PCR results represent the first comparative profile of IgD, IgM, IgZ/T expression over the lifespan of any fish species and the primers and assay parameters reported should prove useful in enabling researchers to rapidly quantify changes in IgH expression in zebrafish models of disease where altered IgH expression is manifested.

  5. In vitro synthesis of IgM rheumatoid factor in response to Staphylococcus aureus, by lymphocytes from healthy adults

    SciTech Connect

    Goldstein, R.; Karsh, J.

    1986-12-01

    Peripheral blood mononuclear cells from 20 healthy adults were tested in vitro for the production of IgM rheumatoid factor (RF) in response to Staphylococcus aureus Cowan I (SAC) or pokeweed mitogen. Fifteen of the 20 normal subjects produced greater than or equal to 4 ng/ml IgM-RF (mean +/- SD 46 +/- 55 ng/ml) in response to SAC, compared with only 2 of 20 who produced greater than or equal to 4 ng/ml IgM-RF (mean +/- SD 2 +/- 4 ng/ml) in response to pokeweed mitogen (P = 0.0001). Separation and reconstitution of autologous T and B cell-enriched fractions, with and without prior T cell irradiation, provided evidence for a radiosensitive T helper/inducer cell involved in the IgM-RF response to SAC in 70% of the normal subjects studied. SAC appears to be a potent stimulus of IgM-RF production, with a cellular mechanism distinct from that of other in vitro systems.

  6. [Nephelometry or turbidimetry for the determination of albumin, ApoA, CRP, haptoglobin, IgM and transthyretin: which choice?].

    PubMed

    Thuillier, F; Demarquilly, C; Szymanowicz, A; Gaillard, C; Boniface, M; Braidy, C; Daunizeau, A; Gascht, D; Gruson, A; Lagabrielle, J-F; Lasnier, E; Lemdani, M; Macchi, V; Poulin, G; de Sainte Hermine, C; Sancho, J; Schellenberg, F; Sevin, O; Vaubourdolle, M

    2008-01-01

    Nephelometry, which is considered as the reference method for serum proteins determination requires a specific equipment. The majority of protein determinations are therefore carried out on biochemistry automats using turbidimetry. The objective of a CNBH group (Collège national de biochimie des hôpitaux) was to compare nephelometry and turbidimetry for 7 automats: 2 nephelometers, the BN Prospec (Dade-Behring) and Immage (Beckman-Coulter) and 5 biochemistry systems using turbidimetry, the Integra and Modular (Roche Diagnostics), the LX20 (Beckman-Coulter), RXL (Dade-Behring) and AU (Olympus). The study was based on the determination of sera collections (albumin, ApoA, CRP, haptoglobin, IgM, transthyretin) of 140 samples each: 110 limpid samples and 30 samples called HLI (hemolytic, lipemic or icteric). Fifteen hospitals took part to this work. An ANOVA analysis on limpid samples and quality control sera concluded to an "automat" effect for the 6 tested proteins but did not show a "method" effect, (i.e. nephelometry versus turbidimetry). On the other hand, the transferability of the results was expected to be better and an effort on the choice of the antibodies and the standardization procedures should be made.

  7. Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients

    PubMed Central

    López, Patricia; de Paz, Banesa; Rodríguez-Carrio, Javier; Hevia, Arancha; Sánchez, Borja; Margolles, Abelardo; Suárez, Ana

    2016-01-01

    Intestinal dysbiosis, characterized by a reduced Firmicutes/Bacteroidetes ratio, has been reported in systemic lupus erythematosus (SLE) patients. In this study, in vitro cultures revealed that microbiota isolated from SLE patient stool samples (SLE-M) promoted lymphocyte activation and Th17 differentiation from naïve CD4+ lymphocytes to a greater extent than healthy control-microbiota. Enrichment of SLE-M with Treg-inducing bacteria showed that a mixture of two Clostridia strains significantly reduced the Th17/Th1 balance, whereas Bifidobacterium bifidum supplementation prevented CD4+ lymphocyte over-activation, thus supporting a possible therapeutic benefit of probiotics containing Treg-inducer strains in order to restore the Treg/Th17/Th1 imbalance present in SLE. In fact, ex vivo analyses of patient samples showed enlarged Th17 and Foxp3+ IL-17+ populations, suggesting a possible Treg-Th17 trans-differentiation. Moreover, analyses of fecal microbiota revealed a negative correlation between IL-17+ populations and Firmicutes in healthy controls, whereas in SLE this phylum correlated directly with serum levels of IFNγ, a Th1 cytokine slightly reduced in patients. Finally, the frequency of Synergistetes, positively correlated with the Firmicutes/Bacteroidetes ratio in healthy controls, tended to be reduced in patients when anti-dsDNA titers were increased and showed a strong negative correlation with IL-6 serum levels and correlated positively with protective natural IgM antibodies against phosphorylcholine. PMID:27044888

  8. Detection of IgM and IgG antibodies against Brucella by dot-ELISA in humans.

    PubMed

    Barbuddhe, S B; Yadava, V K; Singh, D K

    1994-03-01

    Dot-enzyme linked immunosorbent assay (dot-ELISA) with autoclaved extract of B. abortus S99 was used for the detection of Brucella antibodies in human sera. Results were compared with those of STAT, RBPT and CFT. Out of 80 sera 8(10 per cent), 15(18.7 per cent), 20(25 per cent) and 13(16.25 per cent) were found positive by RBPT, STAT, IgM dot-ELISA and IgG dot-ELISA respectively. Out of 74 sera samples tested with CFT 9(12.16 per cent) proved positive. The relative sensitivity and relative specificity in comparison with CFT was found to be 33.33 per cent, 96.92 percent for RBPT, 33.33 per cent and 84.61 per cent for STAT and 88.88 per cent and 76.92 per cent for dot-ELISA, respectively. The dot-ELISA was found to be a more sensitive, economical and a rapid test for screening of human brucellosis under field conditions.

  9. Anti-Acanthamoeba IgG, IgM, and IgA immunoreactivities in correlation to strain pathogenicity.

    PubMed

    Walochnik, J; Obwaller, A; Haller-Schober, E M; Aspöck, H

    2001-08-01

    Several representatives of the genus Acanthamoeba are known as causative agents of Acanthamoeba keratitis and granulomatous amoebic encephalitis. These occur predominantly in the immunocompromised host, but it is still unclear what primes the amoebae for pathogenicity. The aim of this study was to assess possible immunological differences between a highly pathogenic and a nonpathogenic Acanthamoeba strain. A total of 20 sera, including two sera of Acanthamoeba keratitis patients, were tested for anti-Acanthamoeba IgG, IgM, and IgA immunoreactivities using immunoblotting. All sera were positive for Acanthamoeba, revealing two predominant bands at 29 kDa and at 47 kDa, respectively. Interestingly, IgG and particularly IgA immunoreactivity enabled a clear discrimination between the pathogenic and nonpathogenic strains. Moreover, compared to the control sera, the two sera of Acanthamoeba keratitis patients showed rather weak immunoreactivities and they lacked the 29 kDa and the 47 kDa band in the IgA immunoblot against the pathogenic strain. The results of our study support the assumption that immunological predisposition might also be of importance in Acanthamoeba keratitis.

  10. Evaluation of the LDBIO point of care test for the combined detection of toxoplasmic IgG and IgM.

    PubMed

    Chapey, Emmanuelle; Wallon, Martine; Peyron, François

    2017-01-01

    The toxoplasma ICT IgG-IgM rapid diagnostic test for the simultaneous detection of specific toxoplasmic immunoglobulin (Ig) G and IgM was compared with the Architect fully automated chemiluminescence test. Four hundred sera were included, among which 248 scored negative in Architect. The cassettes were easily read with the naked eye. Diagnostic sensitivity and specificity were 97% and 96%, respectively. The test scored 8 false-positive IgG and yielded negative results in 3 sera displaying unspecific IgM in Architect. The LDBIO appears to be a reliable first line test, although the false-positive results for IgG deserve further investigation. Such an easily performed test could be used advantageously for screening for toxoplasmosis in pregnant women.

  11. AL Amyloidosis

    PubMed Central

    2012-01-01

    Definition of the disease AL amyloidosis results from extra-cellular deposition of fibril-forming monoclonal immunoglobulin (Ig) light chains (LC) (most commonly of lambda isotype) usually secreted by a small plasma cell clone. Most patients have evidence of isolated monoclonal gammopathy or smoldering myeloma, and the occurrence of AL amyloidosis in patients with symptomatic multiple myeloma or other B-cell lymphoproliferative disorders is unusual. The key event in the development of AL amyloidosis is the change in the secondary or tertiary structure of an abnormal monoclonal LC, which results in instable conformation. This conformational change is responsible for abnormal folding of the LC, rich in β leaves, which assemble into monomers that stack together to form amyloid fibrils. Epidemiology AL amyloidosis is the most common type of systemic amyloidois in developed countries with an estimated incidence of 9 cases/million inhabitant/year. The average age of diagnosed patients is 65 years and less than 10% of patients are under 50. Clinical description The clinical presentation is protean, because of the wide number of tissues or organs that may be affected. The most common presenting symptoms are asthenia and dyspnoea, which are poorly specific and may account for delayed diagnosis. Renal manifestations are the most frequent, affecting two thirds of patients at presentation. They are characterized by heavy proteinuria, with nephrotic syndrome and impaired renal function in half of the patients. Heart involvement, which is present at diagnosis in more than 50% of patients, leading to restrictive cardiopathy, is the most serious complication and engages prognosis. Diagnostic methods The diagnosis relies on pathological examination of an involved site showing Congo red-positive amyloid deposits, with typical apple-green birefringence under polarized light, that stain positive with an anti-LC antibody by immunohistochemistry and/or immunofluorescence. Due to the

  12. Multiplexed Anti-Toxoplasma IgG, IgM, and IgA Assay on Plasmonic Gold Chips: towards Making Mass Screening Possible with Dye Test Precision

    PubMed Central

    Li, Xiaoyang; Pomares, Christelle; Gonfrier, Géraldine; Koh, Byumseok; Zhu, Shoujun; Gong, Ming

    2016-01-01

    Toxoplasmosis is an infection caused by the protozoan parasite Toxoplasma gondii that can lead to severe sequelae in the fetus during pregnancy. Definitive serologic diagnosis of the infection during gestation is made mostly by detecting T. gondii-specific antibodies, including IgG and IgM, individually in a single serum sample by using commercially available kits. The IgA test is used by some laboratories as an additional marker of acute infection. Most of the commercial tests have failed to reach 100% correlation with the reference method, the Sabin-Feldman dye test for the detection of Toxoplasma IgG antibodies. For Toxoplasma IgM and IgA antibodies, there is no reference method and their evaluation is done by comparing the results of one assay to those of another. There is a need for multiplexed assay platforms, as the serological diagnosis of T. gondii infection does not rely on the detection of a single Ig subtype. Here we describe the development of a plasmonic gold chip with vast fluorescence enhancement in the near-infrared region for simultaneous detection of IgG, IgM, and IgA antibodies against T. gondii in an ∼1-μl serum or whole-blood sample. When 168 samples were tested on this platform, IgG antibody detection sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were all 100%. IgM antibody detection achieved 97.6% sensitivity and 96.9% specificity with a 90.9% PPV and a 99.2% NPV. Thus, the nanoscience-based plasmonic gold platform enables a high-performance, low-cost, multiplexed assay requiring ultrasmall blood volumes, paving the way for the implementation of universal screening for toxoplasmosis infection during gestation. PMID:27008879

  13. Evaluation of the diagnostic value of measuring IgG, IgM, and IgA antibodies to mycobacterial A60 antigen in active tuberculosis.

    PubMed

    Ben-selma, Walid; Harizi, Hedi; Marzouk, Manel; Ben Kahla, Imen; Ben Lazreg, Foued; Ferjeni, Asma; Boukadida, Jalel

    2010-09-01

    The purpose of the present study was to evaluate the clinical usefulness of detection of serum immunoglobulin A (IgA), IgG, and IgM antibodies raised against the mycobacterial A60 antigen for the diagnosis and discrimination of active tuberculosis (TB) from other pulmonary diseases. Three commercially available ELISA kits (IgA, IgG, and IgM) (ANDA Biologicals, Strasbourg, France) were evaluated simultaneously in 246 serum samples from 3 groups of patients: group I, 171 patients with active TB (128 pulmonary TB and 43 extrapulmonary TB); group II, 73 patients with pulmonary non-TB diseases; and group III, 2 leprosies patients. The sensitivities of tests ranged from 31.3% (IgA) to 94% (IgG) in pulmonary TB patients and from 21% (IgA) to 84% (IgG) in extrapulmonary TB patients. The specificities of assays varied from 92% (IgG) to 96% (IgA) in the pulmonary non-TB group. Combination of IgG with IgA and/or IgM does not improve its sensitivity. Clinical use of the A60-based serodiagnostic IgG assay is of great value for the rapid diagnosis and discrimination between active TB and pulmonary non-TB diseases. Moreover, this test could be used to increase diagnostic accuracy, especially for smear-negative TB cases, which are difficult to diagnose.

  14. Gold magnetic nanoparticle conjugate-based lateral flow assay for the detection of IgM class antibodies related to TORCH infections.

    PubMed

    Li, Xingxing; Zhang, Qinlu; Hou, Peng; Chen, Mingwei; Hui, Wenli; Vermorken, Alphons; Luo, Zhiyi; Li, Hong; Li, Qin; Cui, Yali

    2015-11-01

    In this study, a lateral flow immunochromatographic assay (LFIA) system for the detection of immunoglobulin M (IgM) antibodies, related to TORCH [(T)oxoplasmosis, (O)ther agents, (R)ubella (also known as German Measles), (C)ytomegalovirus, and (H)erpes simplex virus infections], based on gold magnetic nanoparticles, was established. Following modification with poly(methacrylic acid), the gold magnetic nanoparticles conjugated with an anti‑human IgM antibody (μ‑chain specific) to construct a probe. A lateral flow assay device was constructed based on these conjugates. IgM antibodies to four types of pathogens, notably toxoplasmosis, rubella virus, cytomegalovirus and herpes simplex virus type 2, were detected using this device. Compared with commercial colloidal gold‑based LFIA strips, our method exhibited higher sensitivity. No interference with triglycerides, hemoglobin and bilirubin occurred, and no cross‑reactivity was noted among the four pathogens. The gold magnetic nanoparticle‑LFIA strips were used to assess 41 seropositive and 121 seronegative serum samples. The sensitivity was 100% (162/162) and the specificity was 100% (162/162). This method cannot only be used for the detection of TORCH IgM-specific antibodies, but it can potentially be developed for use in the diagnosis of other acute or recently identified autoimmune diseases.

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

    PubMed Central

    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. PMID:26973645

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

    PubMed

    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.

  17. Functional capacities of human IgM memory B cells in early inflammatory responses and secondary germinal center reactions.

    PubMed

    Seifert, Marc; Przekopowitz, Martina; Taudien, Sarah; Lollies, Anna; Ronge, Viola; Drees, Britta; Lindemann, Monika; Hillen, Uwe; Engler, Harald; Singer, Bernhard B; Küppers, Ralf

    2015-02-10

    The generation and functions of human peripheral blood (PB) IgM(+)IgD(+)CD27(+) B lymphocytes with somatically mutated IgV genes are controversially discussed. We determined their differential gene expression to naive B cells and to IgM-only and IgG(+) memory B cells. This analysis revealed a high similarity of IgM(+)(IgD(+))CD27(+) and IgG(+) memory B cells but also pointed at distinct functional capacities of both subsets. In vitro analyses revealed a tendency of activated IgM(+)IgD(+)CD27(+) B cells to migrate to B-cell follicles and undergo germinal center (GC) B-cell differentiation, whereas activated IgG(+) memory B cells preferentially showed a plasma cell (PC) fate. This observation was supported by reverse regulation of B-cell lymphoma 6 and PR domain containing 1 and differential BTB and CNC homology 1, basic leucine zipper transcription factor 2 expression. Moreover, IgM(+)IgD(+)CD27(+) B lymphocytes preferentially responded to neutrophil-derived cytokines. Costimulation with catecholamines, carcinoembryonic antigen cell adhesion molecule 8 (CEACAM8), and IFN-γ caused differentiation of IgM(+)IgD(+)CD27(+) B cells into PCs, induced class switching to IgG2, and was reproducible in cocultures with neutrophils. In conclusion, this study substantiates memory B-cell characteristics of human IgM(+)IgD(+)CD27(+) B cells in that they share typical memory B-cell transcription patterns with IgG(+) post-GC B cells and show a faster and more vigorous restimulation potential, a hallmark of immune memory. Moreover, this work reveals a functional plasticity of human IgM memory B cells by showing their propensity to undergo secondary GC reactions upon reactivation, but also by their special role in early inflammation via interaction with immunomodulatory neutrophils.

  18. Serological Profile of HSV-2 in STD Patients: Evaluation of Diagnostic Utility of HSV-2 IgM and IgG Detection

    PubMed Central

    Rashetha; Sucilathangam, G.; Cinthujah, B.; Revathy, C.

    2014-01-01

    Background and Objectives:The present study was undertaken to determine Herpes Simplex Virus-2 seroprevalence in sexually active adults aged 20-49 and to investigate the correlation with sociodemographic characteristics and to find its association with other sexually transmitted diseases especially HIV and also to assess the proportion of primary and reactivated HSV-2 cases. Materials and Methods:This prospective study was carried out for a period of six months in a tertiary care hospital. Serum samples were taken from 91 patients attending the out Patient clinic of the Department of Venereology. The serological testing for HSV-2 was performed on all the specimens by using Euroimmun anti-HSV2 (gG2) IgM ELISA and IgG ELISA. Results: Out of the 91 STD patients in the study group, 18 males (34.62%) and 14 females (36.84%) tested positive for HSV-2 antibodies. Seropositivity rate is 35.16%. More number of HSV-2 positive cases were seen among males, older age, rural residence, low socioeconomic status, single marital status, irregular condom usage during the sexual intercourses with new partners and with higher number of sexual partners during lifetime. HSV-2 IgM alone was positive in three cases, HSV-2 IgG alone was positive in 26 cases and three had a positive HSV-2 IgM and IgG result. Addition of IgM testing increased rate of detecting seroconversion, 31.87%, when only IgG ELISA was used, to 35.16 % patients when IgM test was added. In the study group four cases tested positive for VDRL, and one of them was a known positive case. Among the 55 HIV positive cases in the study group, HSV 2 was positive in 17 cases and among the 36 HIV negative cases HSV 2 was positive in 15 cases. (30.91% and 47.22%).Though the number of HIV cases were high, HSV 2 positivity among them was statistically not significant. Conclusion:The purpose of screening for HSV-2 is not only to identify seropositivity, but to help seropositive people identify symptoms and protect themselves from

  19. Role of IgA, IgG, and IgM antibodies against Haemophilus parainfluenzae antigens in IgA nephropathy.

    PubMed

    Suzuki, S; Gejyo, F; Nakatomi, Y; Odani, S; Sato, H; Arakawa, M

    1996-11-01

    We have recently demonstrated glomerular deposition of outer membranes of Haemophilus parainfluenzae (HP) antigens (OMHP) and the presence of IgA antibody against OMHP in patients with IgA nephropathy (IgA-N). In this study, we analyzed IgA-, IgG-, and IgM-classes of antibodies against OMHP, and the relationship between these antibodies and renal lesions in IgA-N. The subjects included 44 patients with IgA-N and 62 patients with outer glomerular diseases (OGD); the latter group consisted of 23 patients with predominantly IgG or IgM deposits and small amounts of IgA in the mesangium (group A), and 39 with IgG or IgM deposits without IgA (group B). IgA, IgG, and IgM antibodies against OMHP in patients sera were detected by enzyme-linked immunosorbent assay (ELISA). Immunoblotting demonstrated that the IgA, IgG, and IgM antibodies against OMHP in the sera of IgA-N patients bound to components of OMHP with molecular weights of 19.5, 30, and 40.5 kD. The amino acid compositions of these three OMHP components were similar to those reported for the outer membrane protein (OMP) P6 precursor, OMP P5, and OMP P2 (porin) of Haemophilus influenzae. Both IgA-N and group A patients, (i.e. those with IgA-related renal disease), demonstrated a significantly higher level of IgA antibodies against OMHP than did group B patients. However, only IgA-N patients revealed a significant correlation between the IgA-antibody titer and degree of glomerular changes. IgA-N patients with macroscopic hematuria or arterio(lo)sclerosis had a significantly higher IgA antibody titer than other IgA-N patients. There was no relationship between renal lesions and IgG or IgM antibody titers in any group. These findings suggest that IgA antibodies against OMHP are significantly increased in patients with IgA-related renal disease compared to those without mesangial IgA deposits and that a significant relationship between these antibodies and renal lesions exists only in patients with IgA-N.

  20. IgM, lgG and IL-6 profiles in the Trypanosoma brucei brucei monkey model of human African trypanosomiasis.

    PubMed

    Waema, Maxwell W; Maina, Naomi W; Ngotho, Maina; Karanja, Simon M; Gachie, Beatrice M; Maranga, Dawn N; Kagira, John M

    2017-04-01

    Human African trypanosomiasis (HAT) patients manifest immunological profiles, whose variations over time can be used to indicate disease progression. However, monitoring of these biomarkers in human patients is beset by several limitations which can be offset by using chronic animal models. A recent improved monkey model of HAT using a Trypanosoma brucei brucei isolate has been developed but the immunological profile has not been elucidated. The objectives of the current study was to determine the IgM, IgG and IL-6 profiles in blood and cerebrospinal fluid (CSF) in vervet monkeys infected with T. b. brucei. Three vervet monkeys were infected intravenously with 10(5)T. b. brucei, monitored for disease development and subsequently treated 28days post infection (dpi) sub-curatively using diminazene aceturate (DA) to induce late stage disease and curatively treated with melarsoprol (Mel B) at 119 dpi, respectively. Matched serum and cerebrospinal fluid (CSF) samples were obtained at regular intervals and immunospecific IgM, immunoglobulin G (IgG) were quantified by ELISA while IL-6 was assayed using a cytometric bead array (CBA) kit. Results showed that following infection, CSF IgM, IgG, IL-6 and serum IL-6 were significantly (p<0.05) elevated with peak levels coinciding with relapse parasitaemia. The IgG levels increased to reach OD peak levels of 0.442±0.5 at 126 dpi. After curative treatment with MelB, the serum IgM and Ig G levels fell rapidly to attain pre-infection levels within 35 and 49days, respectively. This shows that the profile of these immunoglobulins can be used as an indicator of curative treatment. CSF IL-6 concentrations of infected vervet monkeys showed no significant change (P>0.05) between infection and 35 dpi but levels increased significantly (P<0.05) with the highest level of 55.53pg/ml recorded at112 dpi. IL-6 elevation from 35 dpi may be indicative of parasite neuroinvasion hence can be used as possible candidate marker for late stage disease

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

    PubMed Central

    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 < 0.005). Serum ANG–IgM levels varied widely, but were highly dependent on the concentration of IgM (r = 0.85; P < 0.0005). We found ANG–IgM in the

  2. Detection of IgG and IgM to meningococcal outer membrane proteins in relation to carriage of Neisseria meningitidis or Neisseria lactamica.

    PubMed

    Kremastinou, J; Tzanakaki, G; Pagalis, A; Theodondou, M; Weir, D M; Blackwell, C C

    1999-05-01

    Carriage of non-serogroupable Neisseria meningitidis or Neisseria lactamica induces antibodies protective against meningococcal disease. Antibodies directed against outer membrane proteins are bactericidal and the serotype and subtype outer membrane protein antigens are being examined for their value as vaccine candidates for serogroup B disease. The aim of this study was to examine the effect of carriage of these two Neisseria species among children and young adults on induction of antibodies to outer membrane components from strains causing disease in Greece. Among 53 patients with meningococcal disease, IgG or IgM antibodies were detected by ELISA in 9 of 13 (69%) from whom the bacteria were isolated and 27 of 40 (67%) who were culture-negative. For military recruits (n = 604), the proportion of carriers of meningococci with IgM or IgG to outer membrane proteins was higher than non-carriers, P < 0.05 and P = 0.000000, respectively. Among school children (n = 319), the proportion with IgM or IgG to outer membrane proteins for carriers of meningococci was higher compared with non-carriers, P = 0.000000 and P = 0000043, respectively. Carriage of N. lactamica was not associated with the presence of either IgM or IgG to the outer membrane proteins in the children. The higher proportion of children (50%) with IgM to outer membrane proteins compared with recruits (10%) might reflect more recent exposure and primary immune responses to the bacteria. The lack of association between antibodies to outer membrane proteins and carriage of N. lactamica could reflect observations that the majority of N. lactamica isolates from Greece and other countries do not react with monoclonal typing reagents. Bactericidal antibodies to meningococci associated with high levels of IgG to N. lactamica were found in a previous study; these are thought to be directed to antigens other than outer membrane proteins or capsules and imply antigens such as lipo-oligosaccharide are involved in

  3. Classification of patients with common variable immunodeficiency by B cell secretion of IgM and IgG in response to anti-IgM and interleukin-2.

    PubMed

    Bryant, A; Calver, N C; Toubi, E; Webster, A D; Farrant, J

    1990-08-01

    We have classified patients with common variable immunodeficiency (CVI) on the basis of the ability of their B cells to respond to anti-IgM and interleukin (IL)-2 in vitro. Group A had cells unable to secrete IgM or IgG, Group B secreted IgM alone, and Group C secreted both IgM and IgG. A separate small group of patients lacked peripheral B cells. Where Ig secretion was present with anti-IgM and IL-2, EBV increased it, but where it was absent, EBV only induced IgM secretion in two out of eight Group A patients and IgG in one out of five Group B patients. These classifications are related to the sex of the patient and may represent different loci of the block in B-cell differentiation in CVI.

  4. Characterization of RAG1 and IgM (mu chain) marking development of the immune system in red-spotted grouper (Epinephelus akaara).

    PubMed

    Mao, Ming-Guang; Lei, Ji-Lin; Alex, Perálvarez-Marín; Hong, Wan-Shu; Wang, Ke-Jian

    2012-10-01

    In vertebrates, lymphoid-specific recombinase protein encoded by recombination-activating genes (RAG1/2) plays a key role in V(D)J recombination of the T-cell receptor and B-cell receptor. In this study, both RAG1 and the immunoglobulin M (IgM) mu chain were cloned to characterize their potential role in the immune defense at developmental stages of red-spotted grouper, Epinephelus akaara. The open reading frame (ORF) of E. akaara RAG1 included 2778 nucleotide residues encoding a putative protein of 925 amino acids, while the ORF of the IgM mu chain had 1734 nucleotide residues encoding 578 amino acids including variable (VH) and constant (CH1-CH2-CH3-CH4) regions. E. akaara RAG1 was composed of a zinc-binding dimerization domain (ZDD) with a RING finger and zinc finger A (ZFA) in the non-core region and a nonamer-binding region (NBR), with a zinc finger B (ZFB), the central and C-terminal domains in the core region. Tridimensional models of the ZDD and NBR of E. akaara RAG1 were constructed for the first time in fishes, while a 3D model of the E. akaara IgM mu chain was also clarified. The RAG1 mRNA was only detected in the thymus and kidney of 4-month and 1.5-year old groupers using qPCR, and the RAG1 protein was confirmed using western blotting and immunohistochemistry. The IgM mu mRNA was examined in most tissues except the gonad. RAG1 and IgM mu gene expression were observed at 15 dph (days post-hatching) and 23 dph respectively, and increased to a higher level at 37 dph. In addition, this was the first time that the morphology of the E. akaara thymus was characterized. The oval-shaped thymus of 4-month old fish was clearly seen and there were amounts of T lymphocytes present. The results suggested that the immune action of E. akaara was likely to start to develop around 15 dph to 29 dph. The transcript level of the RAG1 gene and the number of lymphocytes in the thymus between 4-month and 1.5-year old groupers indicated that age-related thymic

  5. Detection of IgE, IgG, IgA and IgM antibodies against raw and processed food antigens

    PubMed Central

    Vojdani, Aristo

    2009-01-01

    Background Despite the first documented case of food allergy to cooked food in 1921 by Prausnitz and Kustner, all commercial food antigens are prepared from raw food. Furthermore, all IgE and IgG antibodies against dietary proteins offered by many clinical laboratories are measured against raw food antigens. Methods We developed an enzyme-linked immunosorbent assay for the measurement of IgE, IgG, IgA and IgM antibodies against raw and processed food antigens. Sera with low or high reactivity to modified food antigens were subjected to myelin basic protein, oxidized low density lipoprotein, and advanced glycation end products (AGE) such as AGE-human serum albumin and AGE-hemoglobin. Results Compared to raw food antigens, IgE antibodies showed a 3–8-fold increase against processed food antigens in 31% of the patients. Similarly, IgG, IgA and IgM antibodies against modified food antigens overall were found at much higher levels than antibody reactions against raw food antigens. Almost every tested serum with high levels of antibodies against modified food antigens showed very high levels of antibodies against myelin basic protein, oxidized low density lipoprotein, AGE-human serum albumin and AGE-hemoglobin. Conclusion We conclude that the determination of food allergy, intolerance and sensitivity would be improved by testing IgE, IgG, IgA and IgM antibodies against both raw and processed food antigens. Antibodies against modified food antigens, by reacting with AGEs and tissue proteins, may cause perturbation in degenerative and autoimmune diseases such as diabetes, atherosclerosis, inflammation, autoimmunity, neurodegeneration and neuroautoimmunity. PMID:19435515

  6. The reanalysis of spectra of GRB 080913 to estimate the neutral fraction of the IGM at a redshift of 6.7

    NASA Astrophysics Data System (ADS)

    Patel, M.; Warren, S. J.; Mortlock, D. J.; Fynbo, J. P. U.

    2010-03-01

    Aims: We reanalyse optical spectra of the z=6.7 gamma-ray burst GRB 080913, adding hitherto unpublished spectra, to reassess the measurement of the neutral fraction of the IGM at high redshifts. Methods: In the data reduction, we take particular care to minimise systematic errors in the sky subtraction, which are evident in the published spectrum, and compromise our analysis. The final combined spectrum has a higher signal-to-noise ration (S/N) than the previously published spectrum by a factor of 1.3. Results: We find a single significant absorption line redward of the Lyα continuum break, which we identify with the ii + Siii λ 0.126 μm blend, at z=6.733. The sharp spectral break at Lyα implies a comparatively low total column density of neutral hydrogen along the line of sight, log({N_HI}/cm-2)<20. We model the absorption with a host-galaxy DLA, surrounded by an ionised region of unknown size r, within the IGM of neutral fraction, xHI. Despite knowing the source redshift, and the improved S/N of the spectrum, when fitting only over wavelengths redward of Lyα, no useful constraints on xHI can be obtained. We consider the possibility of including the ionised region, blueward of Lyα, when constraining the fit. For the optimistic assumption that the ionised region is transparent, τ_GP≪1, we find that the region is of small size r<2 proper Mpc, and we obtain an upper limit to the neutral fraction of the IGM at z=6.7 of x_HI<0.73 at a probability of 90%.

  7. Diagnostic Accuracy of the InBios Scrub Typhus Detect Enzyme-Linked Immunoassay for the Detection of IgM Antibodies in Northern Thailand

    PubMed Central

    Blacksell, Stuart D.; Tanganuchitcharnchai, Ampai; Nawtaisong, Pruksa; Kantipong, Pacharee; Laongnualpanich, Achara; Day, Nicholas P. J.

    2015-01-01

    In this study, we examined the diagnostic accuracy of the InBios Scrub Typhus Detect IgM enzyme-linked immunosorbent assay (ELISA) and determined the optimal diagnostic optical density (OD) cutoffs for screening and diagnostic applications based on prospectively collected, characterized samples from undifferentiated febrile illness patients in northern Thailand. Direct comparisons with the serological gold standard, indirect immunofluorescence assay (IFA), revealed strong statistical correlation of ELISA OD values and IFA IgM titers. Determination of the optimal ELISA cutoff for seroepidemiology or screening purposes compared to the corresponding IFA reciprocal titer of 400 as previously described for Thailand was 0.60 OD, which corresponded to a sensitivity (Sn) of 84% and a specificity (Sp) of 98%. The diagnostic performance against the improved and more-stringent scrub typhus infection criteria (STIC), correcting for low false-positive IFA titers, resulted in an Sn of 93% and an Sp of 91% at an ELISA cutoff of 0.5 OD. This diagnostic ELISA cutoff corresponds to IFA reciprocal titers of 1,600 to 3,200, which greatly reduces the false-positive rates associated with low-positive IFA titers. These data are in congruence with the recently improved serodiagnostic positivity criteria using the Bayesian latent class modeling approach. In summary, the InBios Scrub Typhus Detect IgM ELISA is affordable and easy-to-use, with adequate diagnostic accuracy for screening and diagnostic purposes, and should be considered an improved alternative to the gold standard IFA for acute diagnosis. For broader application, regional cutoff validation and antigenic composition for consistent diagnostic accuracy should be considered. PMID:26656118

  8. Validation of an IgM antibody capture ELISA based on a recombinant nucleoprotein for identification of domestic ruminants infected with Rift Valley fever virus.

    PubMed

    Williams, Roy; Ellis, Charlotte Elizabeth; Smith, Shirley Jacqueline; Potgieter, Christiaan Abraham; Wallace, David; Mareledwane, Vuyokazi Epipodia; Majiwa, Phelix Antipas Ochola

    2011-11-01

    The presence of competent vectors in some countries currently free of Rift Valley fever (RVF) and global changes in climate, travel and trade have increased the risk of RVF spreading to new regions and have emphasised the need for accurate and reliable diagnostic tools for early diagnosis during RVF outbreaks. Highly sensitive viral detection systems like PCR have a limited use during outbreaks because of the short duration of viraemia, whereas antibodies like specific IgM which are serological indicators of acute infection, can be detected for up to 50 days after infection. Using the highly conserved and immunogenic recombinant nucleoprotein of RVF virus in an IgM capture ELISA, the risk of laboratory infection associated with traditional serological methods is avoided. The use of pre-coated/pre-blocked ELISA plates and the conjugation of the recombinant nucleoprotein with horseradish peroxidase simplified and shortened the assay procedure. Results showed the assay to be highly reproducible with a lower detection limit equal to that of a commercial competition ELISA. By receiver operating characteristic (ROC) curve analysis the area under curve (AUC) index was determined as 1.0 and the diagnostic sensitivity and specificity at a PP cut-off value of 4.1 as 100% and 99.78% respectively. The results of this study demonstrated that the IgM capture ELISA is a safe, reliable and highly accurate diagnostic tool which can be used on its own or in parallel with other methods for the early diagnosis of RVF virus infection and also for monitoring of immune responses in vaccinated domestic ruminants.

  9. Single or combined effects of Lactobacillus sakei and inulin on growth, non-specific immunity and IgM expression in leopard grouper (Mycteroperca rosacea).

    PubMed

    Reyes-Becerril, Martha; Ascencio, Felipe; Gracia-Lopez, Vicente; Macias, Ma Esther; Roa, Marcos Cadena; Esteban, María Ángeles

    2014-08-01

    The aim of this study was to evaluate the single or combined effects of Lactobacillus sakei with inulin suitable for immunological in vivo studies in farmed fish. By in vitro assays, L. sakei strain 5-4 showed antibacterial activities against all assayed fish pathogens (except the Vibrio harveyi strain CAIM-1793). L. sakei was able to survive at high fish bile concentrations. Fermentation of the agave inulin resulted in a large increase in number of lactobacilli. For the in vivo study, fish were fed for 8 weeks four practical diets: control diet (control), L. sakei 5-4 (10(7) CFU/g), inulin (1% or 10 g/kg) and L. sakei + inulin (10(7) CFU/g + 10 g/kg). The weight gain showed clearly the synergistic effect of L. sakei 5-4 and inulin at 6 and 8 weeks of treatments. Leopard grouper fed with L. sakei alone or combined with inulin have significantly increased the assayed physiological and humoral immune parameters. By real-time PCR assays, the mRNA transcripts of immunoglobulin M (IgM) were found to be higher expressed in intestine, head kidney, mucus, gill, spleen and skin. Moreover, mRNA expression levels of IgM in head kidney and anterior intestine were measured by real-time PCR. L. sakei 5-4 and L. sakei + inulin supplemented diet up-regulated the expression of IgM at week 4 and 8 in intestine and head kidney, respectively. These results support the idea that the L. sakei 5-4 alone or combined with agave inulin improved growth performance and stimulates the immune system of leopard grouper.

  10. Characteristics Peripheral Blood IgG and IgM Heavy Chain Complementarity Determining Region 3 Repertoire before and after Immunization with Recombinant HBV Vaccine

    PubMed Central

    Yang, Jiezuan; Shi, Bin; He, Xiaoyan; Ma, Rui; Ma, Qingqing; Yao, Xinsheng

    2017-01-01

    Immunization with recombinant HBV vaccine induces specific immune responses in human causing B lymphocytes to produce protective HBsAb, and to form memory B lymphocytes, thereby facilitating HBV immunity in the body. However, B lymphocytes heterogeneity and characteristics are not fully elucidated. In this study, we conducted high-throughput sequencing of BCR heavy chain CDR3 repertoires in 3 healthy volunteers before and after the third immunization with recombinant HBV vaccine. We used Roche 454 Genome Sequencer FLX system to perform a comparative analysis of IgM and IgG H chain CDR3 repertoires. First, we found that the diversity of IgG H chain CDR3 repertoires was 1/6 of IgM on average. Moreover, after the third immunization with HBV vaccine, the diversity of IgG H chain CDR3 repertoires was 1/26 of IgM on average. Second, we detected relatively high levels of HBsAbs in all the healthy volunteers after immunization with HBV vaccine. The volunteers shared a small number of CDR3 sequences before and after immunization, and among each other. However, we did not find completely identical BCR H chain CDR3 amino acid sequences in these volunteers. Lastly, after immunization with recombinant HBV vaccine, the volunteers showed high frequency of IgG H chain CDR3 amino acid sequences mostly resulting from rearrangements of IGHV, IGHD and IGHJ, suggesting that the mechanism of high frequency CDR3 generation might be associated with the maturation of IgG affinity (somatic hypermutation) during the recombinant HBV vaccine-induced B lymphocyte responses. This study identified the characteristics and changes of BCR CDR3 repertoires before and after immunization with HBV vaccine, and evaluated the performance of the sequencing technology for this application. Our findings provide a basis for further research in B lymphocyte generated HBsAb heterogeneity and monitoring the maintenance of memory B lymphocytes. PMID:28114326

  11. Anti-PEG IgM and complement system are required for the association of second doses of PEGylated liposomes with splenic marginal zone B cells.

    PubMed

    Shimizu, Taro; Mima, Yu; Hashimoto, Yosuke; Ukawa, Masami; Ando, Hidenori; Kiwada, Hiroshi; Ishida, Tatsuhiro

    2015-10-01

    The accelerated blood clearance (ABC) phenomenon makes it crucial to use PEGylated liposomes and micelles to deliver drugs. The ABC phenomenon is an immune response against an initial dose of PEGylated liposome, which causes subsequent doses to be rapidly cleared by macrophages in the liver. We recently found that in the early phase of the ABC phenomenon, subsequent doses of PEGylated liposomes were associated with splenic marginal zone (MZ)-B cells and were transported from the MZ to the follicle (FO). In this study, we investigated the underlying mechanisms behind the association of subsequent doses of PEGylated liposomes with MZ-B cells in the spleen. Serum factors, anti-PEG IgM and complement system, were crucial to the association of PEGylated liposomes with MZ-B cells, while the sensitization of MZ-B cells by the first dose of PEGylated liposomes was not significant. It was the complement receptors (CRs) on the MZ-B cells, rather than either the PEG-specific B-cell receptors or the IgM Fc receptors, that were the main contributors to the association between PEGylated liposomes and MZ-B cells. It appeared that anti-PEG IgM would bind to PEGylated liposomes and causes subsequent complement activation, resulting in the formation of immune complexes of PEGylated liposome-anti-PEG IgM-complement. The MZ-B cells then recognized these immune complexes via their CRs. Such an association via CRs might have triggered the transport of the immune complex by MZ-B cells to the FO in the spleen. The information obtained in this study might be useful in the development of an efficient antigen delivery system to usher PEGylated nanoparticles into FO dendritic cells.

  12. Detection of Lassa virus antinucleoprotein immunoglobulin G (IgG) and IgM antibodies by a simple recombinant immunoblot assay for field use.

    PubMed

    Ter Meulen, J; Koulemou, K; Wittekindt, T; Windisch, K; Strigl, S; Conde, S; Schmitz, H

    1998-11-01

    The nucleoprotein of Lassa virus, strain Josiah, was expressed in Escherichia coli as an N-terminally truncated, histidine-tagged recombinant protein. Following affinity purification the protein was completely denatured and spotted onto nitrocellulose membrane. A total of 1 microgram of protein was applied for detection of Lassa virus antibodies (LVA) in a simple immunoblot assay. Specific anti-Lassa immunoglobulin M (IgM) antibodies could be detected by increasing the amount of protein to 5 microgram. A panel of 913 serum specimens from regions in which Lassa virus was endemic and from regions in which Lassa virus was not endemic was used for evaluating the sensitivity and specificity of the LVA immunoblot in comparison to those of an indirect immunofluorescence (IIF) assay. The sera originated from field studies conducted in the Republic of Guinea (570 serum samples) and Liberia (99 serum samples), from inpatients of the clinical department of the Bernhard-Nocht-Institute, Hamburg, Germany (94 serum samples), and from healthy German blood donors (150 serum samples). In comparison to the IIF assay the LVA immunoblot assay had a specificity of 90.0 to 99.3%, depending on the origin of the specimens. The sensitivity was found to be highest for the Guinean samples (90.7%) and was lower for the Liberian samples (75%). Acute Lassa fever was diagnosed by PCR in 12 of 59 (20.3%) patients with fever of unknown origin (FUO) from the Republic of Guinea. On admission to the hospital, nine Lassa fever patients (75%) were reactive by the IgM immunoblot assay. One of the patients was infected with a new Lassa variant, which showed 10.4% variation on the amino acid level in comparison to the prototype strain of Lassa virus, Josiah. Seven PCR-negative patients were reactive by immunoblotting. The positive and negative predictive values of a single IgM immunoblot result for acute, PCR-confirmed Lassa fever were therefore 53.6 and 93.0%, respectively. Because of its high negative

  13. Presence of Mycoplasma fermentans in the bloodstream of Mexican patients with rheumatoid arthritis and IgM and IgG antibodies against whole microorganism

    PubMed Central

    Gil, Constantino; Rivera, Antonio; Bañuelos, David; Salinas, Salvador; García-Latorre, Ethel; Cedillo, Lilia

    2009-01-01

    Background Increasing evidence incriminates bacteria, especially Mycoplasma fermentans, as possible arthritogenic agents in humans. The purpose of this study was to investigate M. fermentans in the bloodstream of patients with rheumatoid arthritis. Methods Two hundred and nineteen blood samples from patients with rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, and healthy individuals were screened by bacterial culture and direct PCR in order to detect mycoplasmas; IgM and IgG against M. fermentans PG18 were also detected by ELISA and Immunoblotting assays in patients with rheumatoid arthritis and healthy individuals. Results Blood samples from patients with antiphospholipid syndrome and healthy individuals were negative for mycoplasma by culture or direct PCR. In blood samples from patients with systemic lupus erythematosus were detected by direct PCR M. fermentans in 2/50 (2%), M. hominis in 2/50 (2%) and U. urealyticum in 1/50 (0.5%). In patients with RA M. fermentans was detected by culture in 13/87 blood samples and in 13/87 by direct PCR, however, there was only concordance between culture and direct PCR in six samples, so M. fermentans was detected in 20/87(23%) of the blood samples from patients with RA by either culture or PCR. Antibody-specific ELISA assay to M. fermentans PG18 was done, IgM was detected in sera from 40/87 patients with RA and in sera of 7/67 control individuals, IgG was detected in sera from 48/87 RA patients and in sera from 7/67 healthy individuals. Antibody-specific immunoblotting to M. fermentans PG18 showed IgM in sera from 35/87 patients with RA and in sera from 4/67 healthy individuals, IgG was detected in sera from 34/87 patients and in sera from 5/67 healthy individuals. Conclusion Our findings show that only M. fermentans produce bacteremia in a high percentage of patients with RA. This finding is similar to those reported in the literature. IgM and IgG against M. fermentans PG18 were more frequent

  14. Autosomal recessive hyper IgM syndrome associated with activation-induced cytidine deaminase gene in three Turkish siblings presented with tuberculosis lymphadenitis - Case report.

    PubMed

    Patiroglu, Turkan; Akar, H Haluk; van der Burg, Mirjam; Unal, Ekrem

    2015-09-01

    The hyper-immunoglobulin M (HIGM) syndrome is a heterogeneous group of genetic disorders characterized by recurrent infections, decreased serum levels of immunoglobulin G (IgG) and IgA, and normal/increased serum levels of IgM. Herein, we describe three Turkish siblings with HIGM syndrome who had a homozygous missense mutation (c.70C>T, p.Arg24Trp) in the activation-induced cytidine deaminase gene which results in autosomal recessive HIGM syndrome. Two of the siblings, sibling 1 and sibling 3, presented with cervical deep abscess and cervical tuberculosis lymphadenitis, respectively.

  15. [A case of pharyngeal-cervical-brachial variant of Guillain-Barré syndrome with positive anti-galactocerebroside (Gal-C) IgM antibody].

    PubMed

    Kasuya, J; Miyazono, T; Takenaga, S; Arimura, K; Osame, M; Kusunoki, S

    1999-05-01

    A 49-year-old man presented with hoarseness, dysphagia, muscle atrophy and weakness of deltoid, trapezius, sternocleidomastoid, rhomboid, anterior serratus, infraspinatus and supraspinatus. Anti-Gal-C IgM antibody was positive in the serum. The other antiganglioside antibodies (GM1, GM2, GM3, GD1a, GD1b, GD3, GT1a, GT1b, GQ1b, GA1, GalNAc-GD1a, GM1b) were negative. Patient contracted pneumonia but whether it was due to mycoplasma was not evident. Plasmapheresis improved his clinical state including a decrease of the antibody. This case was diagnosed pharyngeal-cervical-brachial variant of Guillain-Barré syndrome, and anti-Gal-C antibody seemed to be correlated with the pathogenesis of this syndrome. Gal-C is a major glycolipid of myelin and the cell membrane of the myelin-forming cell (oligodendrocytes and Schwann cells) and is free of specific localization and distribution. The mechanism how the anti-Gal-C IgM antibody induced bulbar paralysis and the symptoms localizing neck and upper limbs remains to be known.

  16. Effects of (Anti) Androgenic Endocrine Disruptors (DEHP and Butachlor) on Immunoglobulin M (IgM) and Leukocytes Counts of Male Rainbow Trout (Oncorhynchus mykiss).

    PubMed

    Ahmadivand, Sohrab; Farahmand, Hamid; Mirvaghefi, Alireza; Eagderi, Soheil; Zargar, Ashkan

    2015-06-01

    The effect of two anti-androgenic endocrine disrupting compounds, i.e. the plasticizer di (2-ethylhexyl) phthalate (DEHP) and herbicide butachlor, were evaluated for their effects on immunoglobulin M (IgM) and leukocytes in male rainbow trout. Also, plasma testosterone (T) concentration was measured to confirm their anti-androgenic effects. In the first experiment, trout were treated with 50 mg/kg (body weight) DEHP intraperitoneally, and in the second one, fish were exposed to 0.39 mg/L butachlor for 10 days. The results showed that T concentrations and white blood cells were significantly lower in fish exposed to either DEHP or butachlor compared to control fish (p < 0.05). Fish showed significantly elevated neutrophil levels and decreased lymphocyte levels in the butachlor (p < 0.05); however, no significant difference was observed in lymphocyte and neutrophils values in the DEHP treatment (p > 0.05). In addition, no significant differences were found in IgM, eosinophil and monocyte parameters in either DEHP or butachlor treatments (p > 0.05). These results confirmed that leukocytes counts can be considered as a novel marker of immunotoxicity triggered by (anti) androgenic endocrine disruptors.

  17. Detection of Anti-Leptospira IgM Antibody in Serum Samples of Suspected Patients Visiting National Public Health Laboratory, Teku, Kathmandu

    PubMed Central

    Sharma, Supriya; Sherchand, Jeevan Bahadur; Upadhyay, Bishnu Prasad; Bhatta, Dwij Raj

    2016-01-01

    Leptospirosis is a globally distributed zoonosis with varied clinical outcomes and multiorgan involvement in humans. In this study conducted from July 2011 to December 2011, 178 serum samples from patients suspected of leptospirosis were tested by Panbio IgM ELISA at National Public Health Laboratory, Kathmandu, out of which 51 (28.65%) were positive for anti-Leptospira IgM antibody. Leptospirosis was more common in people in their 2nd and 3rd decades of their life which together comprised 56.86% of the total positive cases. Most of those tested positive were farmers followed by students and housewives. Both animal contact and water contact seemed to play significant roles in disease transmission. Symptoms were vague with the most common being fever, headache, myalgia, abdominal pain, vomiting, jaundice, and diarrhoea. Life style heavily dominated by agronomical and farming activities in Nepal is conducive to leptospirosis transmission. Leptospirosis seems to be a significant public health problem in Nepal but is underestimated. In resource poor countries like Nepal where laboratories performing MAT or maintaining cultures are rarely available, serological test like ELISA could well depict the scenario of the disease prevalence. PMID:28044080

  18. In men at risk of HIV infection, IgM, IgG1, IgG3, and IgA reach the human foreskin epidermis.

    PubMed

    Lemos, M P; Karuna, S T; Mize, G J; Fong, Y; Montano, S M; Ganoza, C; Lama, J R; Sanchez, J; McElrath, M J

    2016-05-01

    We profiled the humoral response in the penis, an area that has been minimally explored but may be relevant for protecting insertive men against HIV and other sexually acquired infections. Comparing paired tissue samples from 20 men at risk of HIV infection, foreskin contains less immunoglobulin A (IgA) and more IgG2 than colon. Using foreskin dermal and epidermal explants and paired plasma from 17 men, we examined Ig accumulation by normalizing Ig to human serum albumin (HSA) transudation. Dermal IgM, IgG2, IgA, and IgE ratios were greater than that in plasma, suggesting there is local antibody secretion at the dermis. Local Ig transcription was concentrated at the inner rather than the outer foreskin, and inner foreskin Ig ratios did not correlate with blood, indicating that localized production can contribute to the foreskin response. IgM, IgG1, IgG3, and IgA have preferential access to the foreskin epidermis, whereas IgG2, IgG4, and IgE are restricted to the dermis. Lastly, Ad5-specific IgA was selectively present in the colon, whereas foreskin Ad5 IgG was mainly derived from blood, and reached the inner epidermis at higher ratios than the outer (P<0.002). In summary, the foreskin antibody response combines local and systemic sources, and there is selective isotype accumulation in the epidermis.

  19. A somatically mutated human antiganglioside IgM antibody that induces experimental neuropathy in mice is encoded by the variable region heavy chain gene, V1-18.

    PubMed Central

    Willison, H J; O'Hanlon, G M; Paterson, G; Veitch, J; Wilson, G; Roberts, M; Tang, T; Vincent, A

    1996-01-01

    IgM paraproteins associated with autoimmune peripheral neuropathy and anti-Pr cold agglutinins react with sialic acid epitopes present on disialylated gangliosides including GD1b, GT1b, GQ1b, and GD3. A causal relationship between the paraprotein and the neuropathy has never been proven experimentally. From peripheral blood B cells of an affected patient, we have cloned a human hybridoma secreting an antidisialosyl IgM mAb, termed Ha1, that shows identical structural and functional characteristics to its serum counterpart. Variable region analysis shows Ha1 is encoded by the same VH1 family heavy chain gene, V1-18, as the only other known anti-Pr antibody sequence and is somatically mutated, suggesting that it [correction of is] arose in vivo in response to antigenic stimulation. In the rodent peripheral nervous system, Ha1 immunolocalizes to dorsal root ganglia, motor nerve terminals, muscle spindles, myelinated axons, and nodes of Ranvier. After intraperitoneal injection of affinity-purified antibody into mice for 10 d, electrophysiological recordings from the phrenic nerve-hemidiaphragm preparation demonstrated impairment of nerve excitability and a reduction in quantal release of neurotransmitter. These data unequivocally establish that an antidisialosyl antibody can exert pathophysiological effects on the peripheral nervous system and strongly support the view that the antibody contributes to the associated human disease. PMID:8636426

  20. Seroprevalence of anti-Toxoplasma IgG and IgM among individuals who were referred to medical laboratories in Mazandaran province, northern Iran.

    PubMed

    Sharif, Mehdi; Daryani, Ahmad; Ebrahimnejad, Zahra; Gholami, Shirzad; Ahmadpour, Ehsan; Borhani, Samaneh; Lamsechi, Narges

    2016-01-01

    Toxoplasma gondii (T. gondii) is a protozoan parasite that can cause toxoplasmosis in humans. However, there is no current data regarding Toxoplasma infection among individuals who were referred to medical laboratories in Mazandaran province (northern Iran). Therefore, we performed a population-based study of Toxoplasma seroprevalence in this region. A total of 1832 sera samples (from 654 men and 1178 women) were collected from people who were referred to medical laboratories in different cities throughout Mazandaran province between March and July 2012. The serum titers of anti-T. gondii IgG and IgM were measured using enzyme-linked immunosorbent assays. The seroprevalence of anti-Toxoplasma IgG was 55.5%; and 14.4% of the positive samples were seropositive for anti-Toxoplasma IgM. The highest seroprevalence was observed among people who were >50 years old (90.6%), and the lowest seroprevalence was observed among children who were 0-9 years old (9.4%; P<0.001). There was no significant difference in the seroprevalences for each sex in the study population. However, a regional sex-specific difference in seroprevalence was observed between men (54.1%) and women (70.6%; P=0.003) in the western cities of Mazandaran. As the seroprevalence of T. gondii in western and eastern Mazandaran was higher than that in the central cities, there is a need to evaluate the nature of the infection chain in these areas.

  1. In Men at Risk of HIV Infection, IgM, IgG1, IgG3 and IgA Reach the Human Foreskin Epidermis

    PubMed Central

    Lemos, Maria P.; Karuna, Shelly T.; Mize, Gregory J.; Fong, Youyi; Montano, Silvia M.; Ganoza, Carmela; Lama, Javier R.; Sanchez, Jorge; McElrath, M. Juliana

    2015-01-01

    We profiled the humoral response in the penis, an area that has been minimally explored but may be relevant for protecting insertive men against HIV and other sexually-acquired infections. Comparing paired tissue samples from 20 men at risk of HIV infection, foreskin contains less IgA and more IgG2 than colon. Using foreskin dermal and epidermal explants and paired plasma from 17 men, we examined Ig accumulation by normalizing Ig to human serum albumin (HSA) transudation. Dermal IgM, IgG2, IgA, and IgE ratios were greater than in plasma, suggesting there is local antibody secretion at the dermis. Local Ig transcription was concentrated at the inner rather than the outer foreskin, and inner foreskin Ig ratios did not correlate with blood, indicating that localized production can contribute to the foreskin response. IgM, IgG1, IgG3, and IgA have preferential access to the foreskin epidermis, whereas IgG2, IgG4, and IgE are restricted to the dermis. Lastly, Ad5-specific IgA was selectively in the colon; whereas foreskin Ad5 IgG was mainly derived from blood, and reached the inner epidermis at higher ratios than the outer (p<0.002). In summary, the foreskin antibody response combines local and systemic sources and there is selective isotype accumulation in the epidermis. PMID:26509877

  2. [Diagnostic value of the anti-IgM SGPG Elisa (Bühlmann laboratories AG) in 147 sera with a monoclonal IgM anti-MAG/SGPG antibody-associated neuropathy].

    PubMed

    Caudie, C; Bouhour, F; Petiot, P; Gonnaud, P-M; Antoine, J-C; Vial, C

    2007-01-01

    Binding of monoclonal IgM antibodies in serum to antigens of the peripheral nervous system such as MAG and SG(L)PG was measured by various non standardised methods. In this study we evaluated a new commercially available IgM anti-SGPG ELISA (Bühlmann Laboratories AG, Switzerland). The results were compared with three different markers and methods: (1) an in-house thin-layer overlay chromatography for IgM reactivity against sulfated glucuronosyl paragloboside (SGPG) antibodies (gold standard), (2) an indirect immunofluorescent assay for detecting IgM antibodies against myelin, and (3) IgM anti-MAG antibodies, a commercially available Kit based on ELISA technology, manufactured by Bühlmann Laboratories AG. 147 patient sera with anti-MAG/SGPG neuropathy and 121 control sera from patients with peripheral neuropathy were analysed. The anti-SGPG autoantibody ELISA turned out to be a very reliable commercially available test with no technical difficulties and both, excellent sensitivity (0.98), and specificity (0.98) for detecting MAG/SGPG antibody-mediated demyelinating neuropathies. Anti-SGPG antibody titers have pratical implications for both, management and follow-up of neuropathies treated with rituximab.

  3. Role of Serum Mycoplasma pneumoniae IgA, IgM, and IgG in the Diagnosis of Mycoplasma pneumoniae-Related Pneumonia in School-Age Children and Adolescents.

    PubMed

    Lee, Wei-Ju; Huang, Eng-Yen; Tsai, Chih-Min; Kuo, Kuang-Che; Huang, Yi-Chuan; Hsieh, Kai-Sheng; Niu, Chen-Kuang; Yu, Hong-Ren

    2017-01-01

    Mycoplasma pneumoniae is an important causative pathogen of community-acquired pneumonia in children. Rapid and reliable laboratory diagnosis of M. pneumoniae infection is important so that appropriate antibiotic treatment can be initiated to reduce the misuse of drugs and resistance rates. Anti-M. pneumoniae immunoglobulin M (IgM) is an indicator of recent primary infection but can persist for several months after initial infection. It has been suggested that anti-M. pneumoniae immunoglobulin A (IgA) can be a reliable indicator for recent M. pneumoniae infection in adults. We investigated the clinical diagnostic value of M. pneumoniae IgA in school-age children and adolescents with M. pneumoniae-related pneumonia. Eighty children with pneumonia and seropositive for M. pneumoniae IgM or with a 4-fold increase of anti-M. pneumoniae immunoglobulin G (IgG) were enrolled from May 2015 to March 2016. The titers of M. pneumoniae IgA, IgM, and IgG, the clinical features, and laboratory examinations of blood, C-reactive protein, and liver enzymes were analyzed. The initial positivity rates for M. pneumoniae IgM and IgA upon admission to the hospital were 63.6 and 33.8%, respectively. One week after admission, the cumulative positivity rates for M. pneumoniae IgM and IgA increased to 97.5 and 56.3%, respectively. Detection of M. pneumoniae IgM was more sensitive than detection of M. pneumoniae IgA for the diagnosis of M. pneumoniae-related pneumonia in school-age children and adolescents; however, paired sera are necessary for a more accurate diagnosis.

  4. Immunodominant IgM and IgG Epitopes Recognized by Antibodies Induced in Enterovirus A71-Associated Hand, Foot and Mouth Disease Patients

    PubMed Central

    Aw-Yong, Kam Leng; Sam, I-Ching; Koh, Mia Tuang

    2016-01-01

    Enterovirus A71 (EV-A71) is one of the main causative agents of hand, foot and mouth disease (HFMD). Unlike other enteroviruses that cause HFMD, EV-A71 is more frequently associated with severe neurological complications and fatality. To date, no effective licensed antivirals are available to combat EV-A71 infection. Little is known about the immunogenicity of viral non-structural proteins in humans. Previous studies have mainly focused on characterization of epitopes of EV-A71 structural proteins by using immunized animal antisera. In this study, we have characterized human antibody responses against the structural and non-structural proteins of EV-A71. Each viral protein was cloned and expressed in either bacterial or mammalian systems, and tested with antisera by western blot. Results revealed that all structural proteins (VP1-4), and non-structural proteins 2A, 3C and 3D were targets of EV-A71 IgM, whereas EV-A71 IgG recognized all the structural and non-structural proteins. Sixty three synthetic peptides predicted to be immunogenic in silico were synthesized and used for the characterization of EV-A71 linear B-cell epitopes. In total, we identified 22 IgM and four IgG dominant epitopes. Synthetic peptide PEP27, corresponding to residues 142–156 of VP1, was identified as the EV-A71 IgM-specific immunodominant epitope. PEP23, mapped to VP1 41–55, was recognized as the EV-A71 IgG cross-reactive immunodominant epitope. The structural protein VP1 is the major immunodominant site targeted by anti-EV-A71 IgM and IgG antibodies, but epitopes against non-structural proteins were also detected. These data provide new understanding of the immune response to EV-A71 infection, which benefits the development of diagnostic tools, potential therapeutics and subunit vaccine candidates. PMID:27806091

  5. Studies on the In Vivo Effects of Antibody INTERACTION OF IgM ANTIBODY AND COMPLEMENT IN THE IMMUNE CLEARANCE AND DESTRUCTION OF ERYTHROCYTES IN MAN

    PubMed Central

    Atkinson, John P.; Frank, Michael M.

    1974-01-01

    Purified human IgM isoagglutinins were utilized to sensitize 51Cr-labeled erythrocytes so as to produce a known number of complement-fixing sites. These cells were then reinfused into the erythrocyte donor. A minimum of 20 C1-fixing sites/erythrocyte were required for decreased survival. As the amount of antibody coating the erythrocytes was increased, a larger percentage was sequestered. With 80 C1-fixing sites, more than 75% of the injected erythrocytes were removed from the circulation within 10 min. In each case, the clearance pattern consisted of rapid hepatic sequestration followed by a gradual return of a portion of the erythrocytes into the circulation where they survived normally. Clearance was shown to be dependent upon activation of the classical complement pathway, since sensitized cells survived normally in hereditary angioedema patients with low levels of C4 and no detectable C2. Exposure of sensitized cells to fresh serum for 15 min led to the deposition of 550-800 C3 molecules/C1-fixing site. Such cells were immune adherence positive, were agglutinated by anti-C3b, formed rosettes with human alveolar macrophages, and were sequestered in vivo, presumably because of the interaction of cell-bound C3b with the C3b receptor on hepatic macrophages. After exposure to heated serum as a source of the C3b inactivator, the cells were immune adherence negative, were agglutinated only by anti-C3d, did not form rosettes with macrophages, and survived normally in vivo despite, being Coombs positive. Cleavage of cell-bound C3b to C3d may explain the release phase of the IgM clearance pattern. Whereas erythrocytes coated with IgM antibody and complement were previously thought to be sequestered in the liver because of extensive membrane damage, these experiments suggest that clearance is determined by the interaction of erythrocyte-bound complement fragments with specific receptors on hepatic macrophages. Images PMID:4847248

  6. [Obtention of a heterohybridoma for production of type IgM monoclonal antibodies against the D antigen of the Rh system].

    PubMed

    León-González, Graciela; Cruz, Carlos

    2007-03-01

    The objective was to obtain a heterohybridoma capable of producing a monoclonal antibody with IgM type anti-D specificity (Rh system), that could be used as a reactive for hemoclasification. Mononuclear cells (MNC) were extracted from a blood sample of a highly sensitized woman, five days after giving birth to an Rh positive child. These were then transformed with the culture supernatant (CSN) of B05.8 cells, rich in Epstein Barr virus (EBV). Once transformed and in exponential growth, they were fused with K6H6/B5 line cells using PEG 4.000 as a fusing agent in a 1:1 proportion. After fusion, they were seeded in culture plates in order to evaluate the formation of hybrids and the secretion of specific antibodies in the CSN of each well. The efficiency of the fusion was 1.8 x 10(-6), making it possible to obtain an anti-D IgM producing clone, which we named BMS-9. This clone could be maintained in constant culture for three months, producing antibodies in a concentration of 4 microg/mL in de CSN. It was also possible to obtain antibodies with an Artificial Capilar System (ACS) reaching a concentration of 24 microg/mL. Potency was determined using Ror cells. In CSN at immediate centrifugation (IC): 1 x 32, score 52; 15' from incubation at room temperature (RT): 1 x 1,024 score 105. With that ACS product at IC: 1 x 32 score 54; 15' from incubation at RT: 1 x 8.192 score 136; and a 37 degrees C: 1 x 8,192 score 136. Reactivity was detected with red cells D(IIIa), D(IV), D(Va), D(VI) type IV, D(VII), DFR, DNU, STEM+, DAR and DAU. There was no reactivity with red cells D(IIIc), DI(Va), D(V) type II, D(VI) types I, II y III, Ro(HAR), DOL and weak D type II. During field study, no false negative or false positive reactions were detected. A stable heterohybridoma was obtained, producer of IgM type anti-D, with enough qualities to be used in blood typing. Given the excellent qualities of the antibody, we are evaluating dilution media and the addition of type IgG antibodies

  7. Shielding of a lipooligosaccharide IgM epitope allows evasion of neutrophil-mediated killing of an invasive strain of nontypeable Haemophilus influenzae.

    PubMed

    Langereis, Jeroen D; Weiser, Jeffrey N

    2014-07-22

    Nontypeable Haemophilus influenzae is a frequent cause of noninvasive mucosal inflammatory diseases but may also cause invasive diseases, such as sepsis and meningitis, especially in children and the elderly. Infection by nontypeable Haemophilus influenzae is characterized by recruitment of neutrophilic granulocytes. Despite the presence of a large number of neutrophils, infections with nontypeable Haemophilus influenzae are often not cleared effectively by the antimicrobial activity of these immune cells. Herein, we examined how nontypeable Haemophilus influenzae evades neutrophil-mediated killing. Transposon sequencing (Tn-seq) was used on an isolate resistant to neutrophil-mediated killing to identify genes required for its survival in the presence of human neutrophils and serum, which provided a source of complement and antibodies. Results show that nontypeable Haemophilus influenzae prevents complement-dependent neutrophil-mediated killing by expression of surface galactose-containing oligosaccharide structures. These outer-core structures block recognition of an inner-core lipooligosaccharide epitope containing glucose attached to heptose HepIII-β1,2-Glc by replacement with galactose attached to HepIII or through shielding HepIII-β1,2-Glc by phase-variable attachment of oligosaccharide chain extensions. When the HepIII-β1,2-Glc-containing epitope is expressed and exposed, nontypeable Haemophilus influenzae is opsonized by naturally acquired IgM generally present in human serum and subsequently phagocytosed and killed by human neutrophils. Clinical nontypeable Haemophilus influenzae isolates containing galactose attached to HepIII that are not recognized by this IgM are more often found to cause invasive infections. Importance: Neutrophils are white blood cells that specialize in killing pathogens and are recruited to sites of inflammation. However, despite the presence of large numbers of neutrophils in the middle ear cavity and lungs of patients with

  8. Assessment of the independent associations of IgG, IgM and IgA isotypes of anticardiolipin with thrombosis in SLE

    PubMed Central

    Domingues, Vinicius; Magder, Laurence S; Petri, Michelle

    2016-01-01

    Objective The Sydney classification criteria for antiphospholipid syndrome include lupus anticoagulant or moderate-to-high titre anticardiolipin IgG or IgM. We explored the association of all anticardiolipin isotypes, lupus anticoagulant and the combination with venous and arterial thrombosis. Methods Patients with systemic lupus erythematosus (SLE) in a large clinical cohort seen quarterly were repeatedly tested by protocol for anticardiolipin antibodies and lupus anticoagulant. Subgroups of patients were defined based on the geometric mean titres of IgG, IgM, IgA anticardiolipin and lupus anticoagulant expressed in dilute Russell's viper venom time (RVVT) seconds for each patient across all cohort visits. These subgroups were compared with respect rates of thrombosis since diagnosis with SLE. Rate ratios were estimated using Cox Proportional Hazards models. Results Of the 1390 cohort members included, there were 284 thrombotic events observed over 17 025 person-years since diagnosis for a rate of 1.7 events per 100 person-years. Those with a geometric mean titre of IgG anticardiolipin >20 had a significantly elevated rate of thromboses (rate ratio 1.8, p=0.0052), whereas there was no evidence of an association between thromboses and elevated IgM geometric mean (rate ratio 1.2, p=0.40). There were relatively few cohort members with elevated IgA geometric mean but the rate of thromboses in that group was elevated (rate ratio 1.7, p=0.23). The associations between anticardiolipin antibodies and thromboses were strongest when considering venous thromboses. Those with two or more elevated anticardiolipin isotypes or those with both IgG anticardiolipin and RVVT did not appear at higher risk than those with a single elevated marker. Conclusion This study supports previous observations that IgG anticardiolipin and lupus anticoagulant are associated with higher rates of thromboses. Our power to study IgA anticardiolipin was limited due to small number of patients with

  9. What Is ALS?

    MedlinePlus

    ... Javits, actor David Niven, “Sesame Street” creator Jon Stone, boxing champion Ezzard Charles, NBA Hall of Fame ... Help for People with ALS and Caregivers Read stories from families living with ALS Forms of ALS ...

  10. A monoclonal IgM directed against immunodominant catalase B of cell wall of Aspergillus fumigatus exerts anti-A. fumigatus activities.

    PubMed

    Chaturvedi, Ashok K; Kumar, Rohitashw; Kumar, Awanit; Shukla, Praveen K

    2009-11-01

    Aspergillus fumigatus, a ubiquitous fungus, has been reported to cause human diseases like allergic pulmonary aspergillosis, aspergilloma and invasive infection. Limited spectrum and emergence of resistance has become a serious problem with available antifungals. Therefore, an alternative approach is required for successful treatment of mycoses. In the present study, immunogenic protein profile of A. fumigatus cell wall was generated using two-dimensional-gel electrophoresis and three hybridomas producing monoclonal antibodies (MAbs; IgM) were selected after fusion experiments. Of these three MAbs, MAb-7 exhibited potent in vitro inhibitory activity, which was confirmed by MTT assay, fluorescence-activated cell sorter analysis and immuno-fluorescence studies, and the protein was identified as catalase B using MALDI-TOF-MS.

  11. Epitope analysis of Japanese cedar pollen allergen Cry j2 with a human IgM class monoclonal antibody 404-117.

    PubMed

    Chiba, Seiya; Yokoyama, Haruka; Kumazawa, Ayane; Shimmoto, Michie; Naganawa, Yasunori; Shinmoto, Hiroshi

    2017-01-01

    Japanese cedar pollen allergen Cry j2 is a causal allergen of seasonal pollinosis in Japan. To analyze B cell epitopes of Cry j2, we established two human-mouse hybridomas secreting IgM class human monoclonal antibodies to Cry j2. A pin-peptide enzyme-linked immunosorbent assay with synthesized icosa peptides showed that 404-117 monoclonal antibody bound to peptides #11-13 with cry j2 amino acid sequence of 101F-L140. Detailed analysis with octa peptides and alanine substituted peptides indicated that an amino acid sequence of 118FKVD121 was an essential for antibody binding. When K119 (Asn) was substituted with alanine, 404-117 monoclonal antibody did not bind to the alanine substituted peptide. We concluded that the 118FKVD121 sequence might have a very important role in early recognition by Cry j2-specific B cells, which could act as antigen presenting cells.

  12. Renal thrombotic microangiopathies/thrombotic thrombocytopenic purpura in a patient with primary Sjögren's syndrome complicated with IgM monoclonal gammopathy of undetermined significance.

    PubMed

    Koga, Tomohiro; Yamasaki, Satoshi; Nakamura, Hideki; Kawakami, Atsushi; Furusu, Akira; Taguchi, Takashi; Eguchi, Katsumi

    2013-01-01

    Thrombotic microangiopathy (TMA)/thrombotic thrombocytopenic purpura (TTP) is a rare but potentially lethal condition requiring rapid recognition, diagnosis, and initiation of therapy. We experienced a case of a 61-year-old woman with primary Sjögren's syndrome (pSS) complicated with severe renal TMA/TTP following IgM monoclonal gammopathy of undetermined significance (MGUS). She was admitted to our hospital for further evaluation of hypergammaglobulinema, acute renal failure, and severe thrombocytopenia. She had been diagnosed with pSS 13 years prior to admission. Histological examination of her kidney revealed fibrin thrombi in the glomeruli and arterioles, a finding that is consistent with TMA/TTP. The patient was subsequently treated with plasma exchange, which resulted in a successful outcome without any complications. This rare case suggests that it is important to make a therapeutic decision based on appropriate and prompt pathological diagnosis.

  13. Polypyrimidine tract binding protein inhibits IgM pre-mRNA splicing by diverting U2 snRNA base-pairing away from the branch point.

    PubMed

    Zheng, Xuexiu; Cho, Sunghee; Moon, Heegyum; Loh, Tiing Jen; Oh, Huyn Kyung; Green, Michael R; Shen, Haihong

    2014-04-01

    The mouse immunoglobulin (IgM) pre-mRNA contains a splicing inhibitor that bears multiple binding sites for the splicing repressor polypyrimidine tract binding protein (PTB). Here we show that the inhibitor directs assembly of an ATP-dependent complex that contains PTB and U1 and U2 small nuclear RNAs (snRNAs). Unexpectedly, although U2 snRNA is present in the inhibitor complex, it is not base-paired to the branch point. We present evidence that inhibitor-bound PTB contacts U2 snRNA to promote base-pairing to an adjacent branch point-like sequence within the inhibitor, thereby preventing the U2 snRNA-branch point interaction and resulting in splicing repression. Our studies reveal a novel mechanism by which PTB represses splicing.

  14. Frequency of anti-Chlamydia trachomatis antibodies in infertile women referred to Tabriz Al-Zahra hospital

    PubMed Central

    Sattari, Mahtab; Ghiami Rad, Mehdi; Ghasemzadeh, Aaliye; Mohammadoghli Reihan, Zahra

    2017-01-01

    Background: Infertility is one of the major issues in society and its incidence is estimated to be almost 10-15%. Chlamydia trachomatis (C. trachomatis) is an important cause of sexually transmitted diseases leading to infertility. Objective: This study was designed to determine the frequency of anti-C. trachomatis antibodies in infertile women at Al-zahra hospital, Tabriz, Iran. Materials and Methods: In this cross-sectional study, the blood samples were collected randomly from 184 infertile women (case group) and 100 pregnant women (control group). The frequency of specific IgG and IgM anti-C. trachomatis antibodies were evaluated using ELISA method. Results: The frequency of IgG anti-C. trachomatis antibody in the control and case groups was 18% and 35.88%, respectively. IgM anti-C. trachomatis antibody was found in 2% of controls and 5.44% of infertile women. Our results showed the significant differences between the case and control groups in anti-C. trachomatis antibodies (IgG, p=0.035 and IgM, p=0.004). Also, no significant relation was seen between the frequency of anti-C. trachomatis antibodies and age, location, and tubal factor infertility in our two study groups. Conclusion: According to high frequency of antibody anti-C. trachomatis among infertile women in competition to the control group, evaluation and treatment of Chlamydia infections is necessary in these patients. PMID:28280796

  15. Epstein-Barr virus-carrying B cells are large, surface IgM, IgD-bearing cells in normal individuals and acute malaria patients.

    PubMed Central

    Lam, K M; Whittle, H; Grzywacz, M; Crawford, D H

    1994-01-01

    In this study the presence of Epstein-Barr virus (EBV) carrying B lymphocytes in different B-cell subpopulations from peripheral blood was determined by spontaneous outgrowth which gives rise to lymphoblastoid cell lines. In healthy seropositive adults, the EBV-carrying B cell was predominantly within the IgM- and IgD-positive but not the IgG-positive subpopulations. Furthermore, these B lymphocytes were in the low-density (large cell) Percoll fraction. The IgM- and IgD-positive B cell phenotype suggests the EBV-carrying B cells to be circulating virgin B cells recently released from the bone marrow. These B cells have an estimated life span of only 6-8 weeks suggesting that long-term EBV persistence in the body may be the result of infection of a more primitive B-cell type. Similar experiments were carried out in children with acute malaria from the Gambia, West Africa, where Burkitt lymphoma (BL) is endemic in order to determine whether a population of EBV-carrying B cells could be identified which had a similar phenotype to the BL cell. The EBV-carrying B cells in this patient group were also found in the IgM-positive, IgG-negative B-cell subpopulation. The majority of these cells were found in the low-density (large cell) Percoll fraction although in some patients a proportion was derived from the high-density (small cell) fraction. This cellular phenotype is not representative of a BL cell. PMID:7959872

  16. A negative nontreponemal and/or specific antitreponemal IgM test does not exclude active infectious syphilis: evidence from a rabbit infectivity test

    PubMed Central

    Lin, Li-Rong; Tong, Man-Li; Gao, Kun; Zhu, Xiao-Zhen; Fan, Jin-Yi; Zheng, Wei-Hong; Li, Shu-Lian; Lin, Hui-Ling; Liu, Li-Li; Yang, Tian-Ci

    2016-01-01

    Abstract Background: The diagnostic criteria for active infectious syphilis in the clinic are important matter of controversy and debate. So far, clinicians habitually do use the negative results of the nontreponemal and/or the specific antitreponemal IgM as the evidences of disease-free or active infection-free status. Method: We present a case study involving a patient who was admitted to Zhongshan Hospital because of cerebral infarct. Clinical examination indicated he had a history of latent syphilis with negative nontreponemal and specific antitreponemal IgM tests. The cerebrospinal fluid sample from the patient was inoculated into seronegative New Zealand rabbit. Results: Motile Treponema pallidum was detected by a rabbit infectivity test in the patient's cerebrospinal fluid. This syphilis strain was confirmed by DNA subtyping form of “centers for disease control subtype/tp0548 sequence type”, and the strain type was 14d/f. Treatment with benzathine penicillin provided no apparent benefit, but treatment with aqueous crystalline penicillin G, especially recommended for neurosyphilis, led to disease regression. No evidence of cerebral infarct was observed during a 2-year follow-up period. Conclusion: The definitive differential diagnosis of active infectious syphilis should be reconsidered. Moreover, selecting the appropriate penicillin preparation is important because T pallidum can reside in sequestered sites. It is necessary to treat a patient with known invasion of the central nervous system with aqueous crystalline penicillin G, if previous treatment for syphilis failed and patients had some clinical neurological presentation that is otherwise unexplained, but that could represent neurosyphilis. Additional studies are needed to confirm the results in other syphilis patients. PMID:27495107

  17. Avian glycan-specific IgM monoclonal antibodies for the detection and quantitation of type A and B haemagglutinins in egg-derived influenza vaccines.

    PubMed

    Legastelois, Isabelle; Chevalier, Michel; Bernard, Marie-Clotilde; de Montfort, Aymeric; Fouque, Martine; Pilloud, Alexandra; Serraille, Christelle; Devard, Nicolas; Engel, Olivier; Sodoyer, Régis; Moste, Catherine

    2011-12-01

    Two IgM monoclonal antibodies (MAbs), Y6F5 and Y13F9, were selected during a screening of clones obtained immunising BALB/c mice with purified envelop proteins of the A/Sydney/5/97 (H3N2) IVR108 influenza strain. These MAbs recognised avian glycans on the haemagglutinin (HA) of the virus. This broad recognition allowed these MAbs to be used as enzyme-labelled secondary antibody reagents in a strain specific enzyme-linked immunosorbent assay (ELISA) in combination with a capture MAb that recognised and allowed the quantitation of the strain specific HA protein present in an egg-produced influenza vaccine. Advantage was taken of these MAbs to develop a universal ELISA in which the MAbs were used both as capture antibody and as enzyme-labelled secondary antibody to detect and quantify the HA protein of any egg-derived influenza vaccine. These avian-glycan specific IgM MAbs may prove to be particularly useful for determining the HA concentration in monovalent egg-derived pandemic influenza vaccines, in which the HA concentration may be lower than 5μg/ml. The HA detection limit in the ELISA assays developed in this study was 1.9μg/ml, as opposed to the 5μg/ml quantitation limit generally accepted for the standard single-radial-immunodiffusion (SRID) assay, the approved technique for quantifying HA content in influenza vaccines. These ELISAs can also be used to quantify influenza HA formulated with emulsion-based or mineral salt adjuvants that could interfere with HA measurement by the SRID assay.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27307452

  19. Serum levels of immunoglobulins (IgG, IgA, IgM) in Antarctic summer expeditioners and their relationship with seasickness.

    PubMed

    Mishra, K P; Yadav, A P; Shweta; Chanda, Sudipta; Majumdar, D; Ganju, Lilly

    2011-01-01

    The Antarctic continent is full of environmental extremes like isolation, cold, UV exposure, and blizzards etc. The present study was conducted to analyze the effect of ship borne journey and the impact of Antarctic harsh environment on serum immunoglobulin (IgG, IgM, IgA) levels and their relationship with seasickness in Indian expeditioners. It was observed that one month onboard ship journey induced an increase in serum IgA levels and decrease in IgG levels while after being one month off board at the Indian research station Maitri, decreased levels of IgG and increased levels of IgA were found. IgM levels were not altered in comparison to the base line control. Moreover, serum IgG level showed a positive correlation while IgA level showed a negative correlation with seasickness. The stimulation of human peripheral blood mononuclear cells (PBMCs) with serum of expeditioner at different places showed that IgA at lower dose induces the release of pro-inflammatory IL-1β, and IL-6 cytokines from PBMCs while higher dose of IgA decreases proinflammatory cytokine production. The release of anti-inflammatory cytokines TGF-β1 and IL-10 was not significantly altered. Thus, the present study concluded that ship borne journey and Antarctic environment lead to increased serum IgA levels while decreased IgG levels. It also suggests that serum IgA level could be a possible biomarker for environmental stress.

  20. Abu al-Layth al-Libi

    DTIC Science & Technology

    2015-02-01

    Introduction In the tradition of post-9/11 senior Arab militant figures operating in Khurasan (the Afghanistan-Pakistan region), there is little doubt as to...the standing of Libyan jihadi commander Abu al-Layth al-Libi. If Usama bin Ladin and Ayman al-Zawahiri came to be the most prominent Arab -Afghan...Libi, a longtime leader of the Libyan Islamic Fighting Group (LIFG), who rapidly established himself as the champion of the Arab -Afghan milieu after

  1. The presence of MOMA-2+ macrophages in the outer B cell zone and protection of the splenic micro-architecture from LPS-induced destruction depend on secreted IgM.

    PubMed

    Fischer, Michael B; Rüger, Beate; Vaculik, Christine; Becherer, Alexander; Wadsak, Wolfgang; Yanagida, Genya; Losert, Udo M; Chen, Jianzhu; Carroll, Michael C; Eibl, Martha M

    2007-10-01

    The role secretory IgM has in protecting splenic tissue from LPS-induced damage was assessed in mice incapable of secreting IgM but able to express surface IgM and IgD. Within seconds after LPS challenge, 99% of the (131)I-labeled LPS was found in the liver and the spleen of both sIgM-deficient and wild-type mice. In the spleen FITC-labeled LPS was found on the surface of 2F8(+) scavenger receptor macrophages localized in the outer marginal zone, while none of the labeled LPS could be detected on marginal zone ER-TR9(+) and MOMA-1(+) macrophages. An additional population of macrophages, MOMA-2(+), were capable of producing C3 locally in the T and B cell zone after LPS challenge. Local C3 production was regulated, as no C3 was found in splenic tissue of unchallenged mice. Interestingly, in the absence of circulating and locally produced secretory IgM, MOMA-2(+) macrophages of the T and B cell zone failed to establish an additional ring of C3-producing macrophages in the outer B cell zone close to the marginal zone upon LPS challenge. The consequence was a massive destruction of the microarchitecture of the spleen where marginal zones disorganized, lymphoid follicles and T cell zones disrupted and follicular DC (FDC) networks disappeared.

  2. The IgM isotype of anti-annexin A5 antibodies and multiple positivity of conventional antiphospholipid antibodies: increasing the number of clinical manifestations of primary antiphospholipid syndrome.

    PubMed

    Bećarević, Mirjana; Stojanović, Ljudmila; Ignjatović, Svetlana; Dopsaj, Violeta

    2016-05-01

    We evaluated the importance of anti-annexin A5 antibodies (aanxA5 Abs) for clinical (thrombosis and/or recurrent pregnancy loss) and serologic (presence of antiphospholipid antibodies: lupus anticoagulant (LA), anticardiolipin (aCL), and anti-β2 glycoprotein I (aβ2GPI) antibodies) features of patients with primary antiphospholipid syndrome (PAPS). Our study included 70 patients with PAPS according to the international consensus criteria for APS. The mean age of the analyzed patients was 45.97 ± 12.72. The disease duration above 5 years was present in 31/70 of patients. Concentrations of analyzed antibodies were measured by ELISA. Cutoff values were set in accordance to the manufacturers' recommendations. History of recurrent pregnancy loss was associated with double positivity for aanxA5 IgM and LA (χ (2) = 4.000, P = 0.046) and triple positivity for aanxA5 IgM + LA + aβ2GPI IgM (χ (2) = 4.168, P = 0.041). Venous thromboses were associated with triple positivity for aanxA5 IgM + aCLIgG + aβ2GPI IgM (χ (2) = 3.965, P = 0.046). The IgG isotype of aanxA5 Abs was in positive correlation with aCL Abs of the IgG (r = 0.310, P = 0.009) and IgM (r = 0.254, P = 0.034) isotype. The presence of the clinical manifestations of PAPS is increasing with the number of positive conventional aPL and the IgM aanxA5 Abs tests. This new combination of Abs is beneficial even when the number of patients with positivity for aanxA5 Abs is low. This is important in further detection of patients prone to recurrence of thrombotic episodes.

  3. Outbreak of viral hemorrhagic fever caused by dengue virus type 3 in Al-Mukalla, Yemen

    PubMed Central

    2013-01-01

    Background Investigations were conducted by the authors to explore an outbreak of viral hemorrhagic fever (VHF) reported in 2010 from Al-Mukalla city, the capital of Hadramout in Yemen. Methods From 15–17 June 2010, the outbreak investigation period, specimens were obtained within 7 days after onset of illness of 18 acutely ill patients hospitalized with VHF and 15 household asymptomatic contacts of 6 acute cases. Additionally, 189 stored sera taken from acutely ill patients with suspected VHF hospitalized in the preceding 12 months were obtained from the Ministry of Health of Yemen. Thus, a total of 222 human specimens were collected; 207 specimens from acute cases and 15 specimens from contacts. All samples were tested with RT-PCR for dengue (DENV), Alkhumra (ALKV), Rift Valley Fever (RVFV), Yellow Fever (YFV), and Chikungunya (CHIKV) viruses. Samples were also tested for DENV IgM, IgG, and NS1-antigen. Medical records of patients were reviewed and demographic, clinical, and laboratory data was collected. Results Of 207 patients tested, 181 (87.4%) patients were confirmed to have acute dengue with positive dengue NS1-antigen (97 patients, 46.9%) and/or IgM (163 patients, 78.7%). Of the 181 patients with confirmed dengue, 100 (55.2%) patients were IgG-positive. DENV RNA was detected in 2 (1%) patients with acute symptoms; both samples were molecularly typed as DENV type 3. No other VHF viruses were detected. For the 15 contacts tested, RT-PCR tests for the five viruses were negative, one contact was dengue IgM positive, and another one was dengue IgG positive. Of the 181 confirmed dengue patients, 120 (66.3%) patients were males and the median age was 24 years. The most common manifestations included fever (100%), headache (94.5%), backache (93.4%), malaise (88.4%), arthralgia (85.1%), myalgia (82.3%), bone pain (77.9%), and leukopenia (76.2%). Two (1.1%) patients died. Conclusions DENV-3 was confirmed to be the cause of an outbreak of VHF in Al

  4. /Cu-Al System

    NASA Astrophysics Data System (ADS)

    Kish, Orel; Froumin, Natalya; Aizenshtein, Michael; Frage, Nachum

    2014-05-01

    Wettability and interfacial interaction of the Ta2O5/Cu-Al system were studied. Pure Cu does not wet the Ta2O5 substrate, and improved spreading is achieved when relatively a high fraction of the active element (~40 at.% Al) was added. The Al2O3 and AlTaO4 phases were observed at the Ta2O5/Cu-Al interface. A thermodynamic evaluation allowed us to suggest that the lack of wetting bellow 40 at.% Al is due to the presence of a native oxide, which covers the drop. The conditions of the native oxide decomposition and the formation of the volatile Al2O suboxide strongly depend on the vacuum level during sessile drop experiments and the composition of the Cu-Al alloy. In our case, Al contents greater than 40% provides thermodynamic conditions for the formation of Al2O (as a result of Al reaction with Al2O3) and the drop spreading. It was suggested that the final contact angle in the Ta2O5/Cu-Al system (50°) is determined by Ta adsorption on the newly formed alumina interlayer.

  5. Temporal invariance and clonal uniformity of brain and cerebrospinal IgG, IgA, and IgM in multiple sclerosis

    PubMed Central

    1986-01-01

    Elevated cerebrospinal fluid (CSF) IgG and oligoclonal IgG bands on electrophoresis are valuable clinical markers for B cell proliferation in the brains of patients with multiple sclerosis (MS). Using two- dimensional electrophoresis, (2DE) we have established that the humoral immune response in MS brain is characterized by finite clonal complexity for the major Ig classes. An important question is whether this immune response is clonally stable or varies with time, related to the development of new lesions and random entry of B cells into the MS brain. To investigate this, we performed serial electrophoretic studies on CSF obtained from 19 patients with MS; the intervals ranged from 7 to 12 yr, with a mean of 8 yr. These analyses included studies of IgG, IgA, and IgM, and revealed that the humoral immune response in MS is clonally stable over long periods. Spontaneous fluctuations or reduction in CSF IgG levels by drugs did not qualitatively affect B cell clonal proliferation in MS brain, in that dominant bands and spots were not obliterated. It has been asserted that IgG synthesis in MS is nonsense antibody because the spectotypes of IgG isolated from different regions of MS brains differ. Factors other than clonal heterogeneity could account for differences found using one-dimensional analysis. B cell clonal products resolve into unique and well-resolved spots by 2DE; the method is uniquely suitable for analysis of restricted immune responses. Therefore, Ig were isolated from 11 regions of three MS brains and the 2DE patterns were compared. The similarity of the 2DE patterns indicate unequivocally that major clones are distributed uniformly although some clones are more prominent in some brain areas. IgA and IgM isolated from the same areas also showed similar patterns. Furthermore, the patterns of light and heavy chains in brain regions differed from serum but were similar to the autologous CSF, providing new evidence that CSF IgG in MS derives from synthesis

  6. A case of severe chronic inflammatory demyelinating polyradiculoneuropathy with monoclonal gammopathy of undetermined significance with alternating immunoglobulin class to IgM from IgA.

    PubMed

    Hayashi, Shintaro; Nagamine, Shun; Makioka, Kouki; Kusunoki, Susumu; Okamoto, Koichi

    2016-09-29

    A 71-year-old woman with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with IgA-λ monoclonal gammopathy of undetermined significance (MGUS) showed the acute development of tetraplegia, respiratory failure, and a marked fluctuation of the blood pressure. Intravenous (IV) high-dose steroid therapy (methylprednisolone: 1 g/day × 3 days), followed by oral prednisolone (PSL) (40 mg/day), and IV immunoglobulin (IVIg, 0.4 g/kg/day × 5 days) administrations resulted in the amelioration of these symptoms. However, they soon relapsed, which eventually led to complete tetraplegia and the need for mechanical ventilation. At this time, serum components of IgA-λ and IgM-λ were biclonally positive. Seven courses of plasma exchange and the alternative administration of dexamethasone (12 mg/day) and methtorexate (15 mg/week) were conducted, but with no significant improvement. Nine months after admission, she showed totally-locked in syndrome. Cryo-preserved serum obtained at this time showed high titers of IgM class antibodies against ganglioside (GD3 +++, GT1a ++++, GT1b ++, GQ1b +++, and GD1b +++), which had been negative on admission. Biopsy of the left sural nerve showed moderate reductions of large and small myelinated fibers with no inflammation, no depositions of amyloid, IgG, IgA, or IgM, and teased fiber findings revealed neither myelin ovoids nor segmental demyelination. Alternatively, melphalan at 5 mg and PSL at 32 mg were administered, with no amelioration, while serum IgA-λ monoclonal protein diminished, and IgM-λ M protein positivity was continuously observed. She frequently developed sepsis; therefore, we could no longer continue any immunosupressive therapies, but monthly IVIg administrations were given. Twelve months after admission, her neurological symptoms gradually improved and she was weaned off of mechanical ventilation. Eighteen months after admission, her muscle strength corresponded to 2 on manual muscle testing

  7. Quantitative immunohistochemical assessment of IgA, IgM, IgG and antigen-specific immunoglobulin secreting plasma cells in pig small intestinal lamina propria.

    PubMed

    Bianco, C; Felice, V; Panarese, S; Marrocco, R; Ostanello, F; Brunetti, B; Muscatello, L V; Leotti, G; Vila, T; Joisel, F; Sarli, G

    2014-08-15

    Intestinal immune response plays an important defensive role for pathogens, particularly for those transmitted by the oro-faecal route or for foecal shedding modulation. This work examined three parts of intestine from twelve gilts experimentally infected with PCV2-spiked semen, six vaccinated (V group) and six unvaccinated (NV group) against PCV2, 29 and 53 days post infection (DPI). An immunohistochemical investigation for IgA-, IgG- and IgM-antibody bearing plasma cells (PCs) was run on intestinal samples coupled with a sandwich immunohistochemical method to reveal anti-PCV2 antibody-secreting PCs. Plasma cell density was compared in the two groups of animals at 29 and 53 DPI. The IgA, IgG and IgM PC density did not differ between groups but displayed an increase from the upper (villus) to the lower part of the crypts while a decreasing trend in PC density was identified from duodenum to ileum. In the NV group, no increase in anti-PCV2 PC density was demonstrable in the two sampling moment: the amounts of lamina propria PCV2-specific antibody-producing PCs remained constant, 10.55 ± 4.24 and 10.06 ± 5.01 at 29 DPI and 53 DPI, respectively. In the V group a significant increase in PCV2-specific antibody-producing PCs was observed over time. The amounts of PCV2-specific antibody-producing PCs increased from 9.37 ± 13.36 at 29 DPI to 18.76 ± 15.83 at 53 DPI. The data on IgA, IgM and IgG PC counts can be considered reference values in a population of adult pigs. The sandwich method can be proposed as a technique able to identify specific antibody-secreting PCs in formalin-fixed paraffin-embedded tissues. A practical application of the sandwich method is the demonstration of a "booster-like" response of the lamina propria in vaccinated compared to unvaccinated animals. After virus challenge, vaccination induced an increase in the number of PCs containing specific anti-PCV2 antibodies at the level of intestinal mucosa.

  8. Initial Symptoms of ALS

    MedlinePlus

    ... Chapters Certified Centers and Clinics Support Groups About ALS About Us Our Research In Your Community Advocate ... Diagnosis En español Symptoms The initial symptoms of ALS can be quite varied in different people. One ...

  9. Lou Gehrig's Disease (ALS)

    MedlinePlus

    ... 1930s. People in England and Australia call ALS motor neurone disease (MND). The French refer to it ... about ALS in 1869. Lou Gehrig's disease damages motor neurons in the brain and spinal cord. Motor ...

  10. Hospital population screening reveals overrepresentation of CD5(-) monoclonal B-cell lymphocytosis and monoclonal gammopathy of undetermined significance of IgM type.

    PubMed

    Voigtlaender, Minna; Vogler, Birthe; Trepel, Martin; Panse, Jens; Jung, Roman; Bokemeyer, Carsten; Bacher, Ulrike; Binder, Mascha

    2015-09-01

    Monoclonal B-cell lymphocytosis (MBL) and monoclonal gammopathy of undetermined significance (MGUS) result from clonal expansions of mature B or plasma cells. Here, we set out to determine the immunophenotypic/monoclonal immunoglobulin (M protein) features and co-prevalence of MBL and MGUS in a hospital-based cohort of 1909 non-hematooncological patients. Of the evaluable cases, 3.8 % showed evidence for MBL by immunophenotyping, while 9.8 % were screened positive for M protein by immunofixation. With six concomitant cases (0.4 %), MBL and MGUS were not statistically associated. At least in two of these coincident cases, MBL and MGUS were of different clonal origin since both clones had divergent light chain restriction. CD5(-) MBL (57.1 %) and IgM+ MGUS (24.7 %) were strikingly overrepresented compared to population-based screenings and did not progress to overt lymphoma or myeloma during the observation period (mean follow-up of 117 weeks or 110 weeks, respectively). Prevalence and phenotypes suggest that a substantial proportion of incidental MBL and MGUS in hospitalized patients may be attributed to transiently expanded B-cell clones in the context of disease-related immune stimulation rather than reflecting veritable precursors of clonal B-cell malignancies.

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

    PubMed

    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.

  12. Defective expression of the CD40 ligand in X chromosome-linked immunoglobulin deficiency with normal or elevated IgM.

    PubMed Central

    Fuleihan, R; Ramesh, N; Loh, R; Jabara, H; Rosen, R S; Chatila, T; Fu, S M; Stamenkovic, I; Geha, R S

    1993-01-01

    B lymphocytes from patients with X chromosome-linked immunoglobulin deficiency with normal or elevated serum IgM are unable to switch from the synthesis of IgM/IgD to that of other immunoglobulin isotypes. Isotype switch recombination was evaluated in three affected males by examining interleukin 4-driven IgE synthesis. T-cell-dependent IgE synthesis was completely absent in the B lymphocytes of the patients. In contrast, CD40 mAb plus interleukin 4 induced the patients' B cells to synthesize IgE and to undergo deletional switch recombination. Because interaction between CD40 and its ligand on activated T cells is critical for T-cell-driven isotype switching, we examined CD40 ligand expression. In contrast to normal T cells, lymphocytes from the patients expressed no detectable CD40 ligand on their surface after stimulation with phorbol 12-myristate 13-acetate and ionomycin, although the mRNA of the ligand was expressed normally. These results suggest that defective expression of the CD40 ligand underlies the failure of isotype switching in this disease. Images Fig. 1 Fig. 3 PMID:7681587

  13. Immunohistochemical detection of IgM and IgG in lung tissue of dogs with leptospiral pulmonary haemorrhage syndrome (LPHS).

    PubMed

    Schuller, Simone; Callanan, John J; Worrall, Sheila; Francey, Thierry; Schweighauser, Ariane; Kohn, Barbara; Klopfleisch, Robert; Posthaus, Horst; Nally, Jarlath E

    2015-06-01

    Leptospiral pulmonary haemorrhage syndrome (LPHS) is a severe form of leptospirosis. Pathogenic mechanisms are poorly understood. Lung tissues from 26 dogs with LPHS, 5 dogs with pulmonary haemorrhage due to other causes and 6 healthy lungs were labelled for IgG (n=26), IgM (n=25) and leptospiral antigens (n=26). Three general staining patterns for IgG/IgM were observed in lungs of dogs with LPHS with most tissues showing more than one staining pattern: (1) alveolar septal wall staining, (2) staining favouring alveolar surfaces and (3) staining of intra-alveolar fluid. Healthy control lung showed no staining, whereas haemorrhagic lung from dogs not infected with Leptospira showed staining of intra-alveolar fluid and occasionally alveolar septa. Leptospiral antigens were not detected. We conclude that deposition of IgG/IgM is demonstrable in the majority of canine lungs with naturally occurring LPHS, similar to what has been described in other species. Our findings suggest involvement of the host humoral immunity in the pathogenesis of LPHS and provide further evidence to support the dog as a natural disease model for human LPHS.

  14. Flow cytometry-based algorithm to analyze the anti-fixed Toxoplasma gondii tachyzoites IgM and IgG reactivity and diagnose human acute toxoplasmosis.

    PubMed

    Silva-dos-Santos, Priscila Pinto; Barros, Geisa Baptista; Mineo, José Roberto; de Oliveira Silva, Deise Aparecida; Menegaz, Mauro Hygino Weinert; Serufo, José Carlos; Dietze, Reynaldo; Martins-Filho, Olindo de Assis; Lemos, Elenice Moreira

    2012-04-30

    In the present study we evaluated the performance of a flow cytometry-based algorithm as a new serological approach to detect antibodies to T. gondii and specific IgG avidity to diagnose acute toxoplasmosis. The results showed that using FC-AFTA-IgM assay, all serum samples from patients with acute toxoplasmosis demonstrated seropositivity, whereas 90% of patients with chronic infection and 100% of non-infected individuals presented negative results. Thus, only 10% of patients with chronic toxoplasmosis showed residual IgM, in contrast with other methodologies used to diagnosis acute toxoplasmosis. On the order hand, FC-AFTA-IgG assay as well as FC-AFTA-IgG subclasses is unlikely to discriminate acute from chronic toxoplasmosis. We have also evaluated the performance of FC-AFTA-IgG avidity as a tool to exclude chronic toxoplasmosis in patients with positive FC-AFTA-IgM. Our data showed an excellent performance of FC-AFTA-IgG avidity employing the cut-off of 60% for Avidity Index (AI) with sensitivity and specificity of 100%. All serum samples from patients presenting acute toxoplasmosis showed low avidity index (AI≤60%), whereas all chronic patients showed high avidity index (AI>60%). The outstanding performance indexes of this novel flow cytometry-based algorithm support its use as a non-conventional alternative serological approach to diagnose human acute toxoplasmosis.

  15. Adjuvant Effect of Quillaja saponaria Saponin (QSS) on Protective Efficacy and IgM Generation in Turbot (Scophthalmus maximus) upon Immersion Vaccination

    PubMed Central

    Wang, Yujuan; Wang, Xiuhua; Huang, Jie; Li, Jun

    2016-01-01

    The adjuvant effect of Quillaja saponaria saponin (QSS) on protection of turbot fry was investigated with immersion vaccination of formalin-killed Vibrio anguillarum O1 and various concentrations of QSS (5, 25, 45 and 65 mg/L). Fish were challenged at days 7, 14 and 28 post-vaccination. Significantly high relative percent of survival (RPS) ((59.1 ± 13.6)%, (81.7 ± 8.2)%, (77.8 ± 9.6)%) were recorded in the fish that received bacterins immersion with QSS at 45 mg/L, which is comparable to the positive control group vaccinated by intraperitoneal injection (IP). Moreover, a remarkably higher serum antibody titer was also demonstrated after 28 days in the vaccinated fish with QSS (45 mg/L) than those vaccinated fish without QSS (p < 0.05), but lower than the IP immunized fish (p < 0.05). Significant upregulation of IgM gene expression has also been identified in the tissues of skin, gill, spleen and kidney from the immunized fish in comparison to the control fish. Taken together, the present study indicated that QSS was able to dramatically evoke systemic and mucosal immune responses in immunized fish. Therefore, QSS might be a promising adjuvant candidate for fish vaccination via an immersion administering route. PMID:26950114

  16. B cell antigen receptors of the IgM and IgD classes are clustered in different protein islands that are altered during B cell activation.

    PubMed

    Maity, Palash Chandra; Blount, Amy; Jumaa, Hassan; Ronneberger, Olaf; Lillemeier, Björn F; Reth, Michael

    2015-09-15

    The B cell antigen receptors (BCRs) play an important role in the clonal selection of B cells and their differentiation into antibody-secreting plasma cells. Mature B cells have both immunoglobulin M (IgM) and IgD types of BCRs, which have identical antigen-binding sites and are both associated with the signaling subunits Igα and Igβ, but differ in their membrane-bound heavy chain isoforms. By two-color direct stochastic optical reconstruction microscopy (dSTORM), we showed that IgM-BCRs and IgD-BCRs reside in the plasma membrane in different protein islands with average sizes of 150 and 240 nm, respectively. Upon B cell activation, the BCR protein islands became smaller and more dispersed such that the IgM-BCRs and IgD-BCRs were found in close proximity to each other. Moreover, specific stimulation of one class of BCR had minimal effects on the organization of the other. These conclusions were supported by the findings from two-marker transmission electron microscopy and proximity ligation assays. Together, these data provide evidence for a preformed multimeric organization of BCRs on the plasma membrane that is remodeled after B cell activation.

  17. Triggering of monoclonal human lymphoma B cells with antibodies to IgM heavy chains: differences of response obtained with monoclonal as compared to polyclonal antibodies.

    PubMed Central

    Godal, T; Ruud, E; Heikkilä, R; Funderud, S; Michaelsen, T; Jefferis, R; Ling, N R; Hildrum, K

    1983-01-01

    A comparative study of human B lymphoma cells activation by monoclonal (murine hybridoma) antibodies to mu heavy chains (Ma-mu) as compared to polyclonal (rabbit) antibodies to mu heavy chains (Ra-mu) has been carried out. Early events related to calmodulin activation such as 86Rb influx and changes in cell volume at 4 h could be induced by Ma-mu. One antibody (AF6) approached Ra-mu with regard to the strength of response obtained. However, Ma-mus including AF6 were deficient in inducing DNA synthesis under conditions where this was achieved with Ra-mu. Studies in one lymphoma, where stimulation of re-expressed surface IgM could be studied, revealed that Ma-mu was deficient in stimulating re-expressed sIgM. These findings raise questions with regard to polyclonal antibody to surface Ig as a model for B cell triggering by antigen and suggest that antigen-induced B cell triggering may be more complex than indicated by previous studies with polyclonal antibody. PMID:6418424

  18. Isolation of 1E4 IgM Anti-Fasciola hepatica Rediae Monoclonal Antibody from Ascites: Comparison of Two Purification Protocols.

    PubMed

    Alba, Annia; Marcet, Ricardo; Otero, Oscar; Hernández, Hilda M; Figueredo, Mabel; Sarracent, Jorge

    2016-02-01

    Purification of immunoglobulin M (IgM) antibodies could be challenging, and is often characterized by the optimization of the purification protocol to best suit the particular features of the molecule. Here, two different schemes were compared to purify, from ascites, the 1E4 IgM monoclonal antibody (mAb) previously raised against the stage of redia of the trematode Fasciola hepatica. This immunoglobulin is used as capture antibody in an immunoenzymatic assay to detect parasite ongoing infection in its intermediate hosts. The first purification protocol of the 1E4 mAb involved two chromatographic steps: an affinity chromatography on a Concanavalin A matrix followed by size exclusion chromatography. An immunoaffinity chromatography was selected as the second protocol for one-step purification of the antibody using the crude extract of adult parasites coupled to a commercial matrix. Immunoreactivity of the fractions during purification schemes was assessed by indirect immunoenzymatic assays against the crude extract of F. hepatica rediae, while purity was estimated by protein electrophoresis. Losses on the recovery of the antibody isolated by the first purification protocol occurred due to protein precipitation during the concentration of the sample and to low resolution of the size exclusion molecular chromatography step regarding this particular immunoglobulin. The immunoaffinity chromatography using F. hepatica antigens as ligands proved to be the most suitable protocol yielding a pure and immunoreactive antibody. The purification protocols used are discussed regarding efficiency and difficulties.

  19. Antigen-specific Treg regulate Th17-mediated lung neutrophilic inflammation, B cell recruitment and polymeric IgA and IgM levels in the airways

    PubMed Central

    Jaffar, Zeina; Ferrini, Maria E.; Girtsman, Teri A.; Roberts, Kevan

    2010-01-01

    Summary Th17 cells play key roles in mediating autoimmunity, inflammation and mucosal host defense against pathogens. To determine whether naturally occurring Treg (nTreg) limit Th17-mediated pulmonary inflammation, OVA-specific CD4+ Th17 cells and expanded CD4+CD25+Foxp3+ nTreg were cotransferred into BALB/c mice that were then exposed to OVA aerosols. Th17 cells, when transferred alone, accumulated in the lungs and posterior mediastinal LN and evoked a pronounced airway hyperreactivity (AHR) and neutrophilic inflammation, characterized by B cell recruitment and elevated IgA and IgM levels. Cotransfer of antigen-specific nTreg markedly reduced the Th17-induced pulmonary inflammation and associated neutrophilia, B cell influx and polymeric Ig levels in the airways, but did not inhibit AHR. Moreover, the regulation appeared restricted to the site of mucosal inflammation, since transfer of nTreg did not affect the Th17 response developing in the lung draining LN, as evidenced by unaltered levels of IL-17 production and low numbers of Foxp3+ Treg. Our findings suggest a crucial role for Th17 cells in mediating airway B cell influx and IgA response and demonstrate that antigen-specific nTreg suppress Th17-mediated lung inflammation. These results provide new insights into how Th17 responses are limited and may facilitate development of novel approaches for controlling Th17-induced inflammation. PMID:19830731

  20. Towards Universal Screening for Toxoplasmosis: Rapid, Cost-effective and Simultaneous Detection of Toxoplasma Anti-IgG, IgM and IgA Antibodies Using Very Small Serum Volumes

    EPA Pesticide Factsheets

    No dataset associated with this publication.This dataset is associated with the following publication:Augustine, S. Towards Universal Screening for Toxoplasmosis: Rapid, Cost-effective and Simultaneous Detection of Toxoplasma Anti-IgG, IgM and IgA Antibodies Using Very Small Serum Volumes. JOURNAL OF CLINICAL MICROBIOLOGY. American Society for Microbiology, Washington, DC, USA, 56(7): 1-2, (2016).

  1. Skin Injuries 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

    PubMed Central

    Kiang, Juliann G.; Ledney, G. David

    2013-01-01

    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. PMID:24175013

  2. Resistance to complement-mediated killing and IgM binding to non-typeable Haemophilus influenzae is not altered when ascending from the nasopharynx to the middle ears in children with otitis media.

    PubMed

    Langereis, Jeroen D; van Dongen, Thijs M A; Stol, Kim; Venekamp, Roderick P; Schilder, Anne G M; Hermans, Peter W M

    2013-12-01

    We have previously found that non-typeable Haemophilus influenzae (NTHi) collected from the middle ear of children with otitis media (OM) exhibit increased levels of complement resistance compared to NTHi collected from the nasopharynx. However, it is unknown whether bacteria develop complement resistance in the middle ear, or whether resistance is present when residing in the nasopharynx. The objective of this study was to investigate whether the levels of complement resistance of isolates collected from the middle ear were similar to those of isolates from the nasopharynx with an identical MLST type. We included 62 children with recurrent acute OM, chronic OM with effusion or acute tympanostomy tube otorrhea. NTHi was simultaneously isolated from the nasopharynx and middle ear fluid. MLST, resistance to complement-mediated killing, IgG binding, IgM binding and phosphorylcholine expression was determined. In 41 children, NTHi isolated from the middle ear and nasopharynx showed to have an identical MLST type. Isolates collected from the middle ear showed a highly similar level of complement resistance and IgM binding with isolates collected from the nasopharynx, whereas this was not the case for IgG binding and phosphorylcholine incorporation into lipooligosaccharide. Resistance to complement-mediated killing and IgM binding of NTHi isolates with an identical MLST type collected from the middle ear and nasopharynx of children with OM was highly similar.

  3. Generation of monoclonal murine anti-DNP-IgE, IgM and IgG1 antibodies: biochemical and biological characterization.

    PubMed Central

    Bohn, A; König, W

    1982-01-01

    Monoclonal DNP-specific IgG (lambda 2 epsilon 2), IgM (kappa 2 mu2) and IgG [kappa 2 (gamma 1)2] were isolated fom the culture supernatant of hybridomas by affinity chromatography with 2,4-dinitrophenol bovine serum albumin (DNP-BSA) sepharose and characterized by biochemical and biological methods. The molecular weights were 84,200 for the epsilon chain, 55,400 for the gamma chain and 77,500 for the mu chain as determined by sodium dodecylsulphate polyacrylamide del electrophoresis (SDS-PAGE). The association constants for [3H]-DNP-lysine determined by equilibrium dialysis were 0 . 87 X 10(7) l/mol for IgE and 1 . 91 X 10(8) 1/mol for IgG1. The isoelectric focusing of the purified monoclonal antibodies revealed for IgG1 seven bands at a pH range of 6 . 3 - 7 . 2 and for IgE sixteen bands at a pH range of 4 . 5 to 6 . 8. the binding of 125I-anti-IgE to rat basophilic leukaemia (RBL) and rat mast cells which had been preincubated with various amounts of monoclonal IgE was studied. At saturation conditions of IgE, about 2 . 14 X 10(5) molecules of anti-IgE were bound per rat mast cell. Rat mast cells coated with monoclonal anti-DNP IgE were triggered for the release of histamine in the presence of either the antigen or guinea-pig anti-mouse IgE. A mutual inhibition of the passive cutaneous anaphylaxis (PCA) reaction in the rat by either mixing mouse reaginic serum directed against ovalbumin or rat reaginic serum directed against Nippostrongylus brasiliensis with monoclonal mouse anti-DNP IgE was demonstrated. Images Figure 2 Figure 7 Figure 8 PMID:6180975

  4. Simultaneous binding of the anti-cancer IgM monoclonal antibody PAT-SM6 to low density lipoproteins and GRP78.

    PubMed

    Rosenes, Zachary; Mok, Yee-Foong; Yang, Shuo; Griffin, Michael D W; Mulhern, Terrence D; Hatters, Danny M; Hensel, Frank; Howlett, Geoffrey J

    2013-01-01

    The tumour-derived monoclonal IgM antibody PAT-SM6 specifically kills malignant cells by an apoptotic mechanism linked to the excessive uptake of plasma lipids. The mechanism is postulated to occur via the multi-point attachment of PAT-SM6 to the unfolded protein response regulator GRP78, located on the surface of tumour cells, coupled to the simultaneous binding of plasma low density lipoprotein (LDL). We prepared and characterised LDL and oxidized LDL using sedimentation velocity and small-angle X-ray scattering (SAXS) analysis. Enzyme-linked immunosorbent (ELISA) techniques indicated apparent dissociation constants of approximately 20 nM for the binding of LDL or oxidized LDL to PAT-SM6. ELISA experiments showed cross competition with LDL inhibiting PAT-SM6 binding to immobilised GRP78, while, in the reverse experiment, GRP78 inhibited PAT-SM6 binding to immobilized LDL. In contrast to the results of the ELISA experiments, sedimentation velocity experiments indicated relatively weak interactions between LDL and PAT-SM6, suggesting immunoabsorbance to the microtiter plate is driven by an avidity-based binding mechanism. The importance of avidity and the multipoint attachment of antigens to PAT-SM6 was further investigated using antigen-coated polystyrene beads. Absorption of GRP78 or LDL to polystyrene microspheres led to an increase in the inhibition of PAT-SM6 binding to microtiter plates coated with GRP78 or LDL, respectively. These results support the hypothesis that the biological action of PAT-SM6 in tumour cell apoptosis depends on the multivalent nature of PAT-SM6 and the ability to interact simultaneously with LDL and multiple GRP78 molecules clustered on the tumour cell surface.

  5. Diagnosis of Kyasanur forest disease by nested RT-PCR, real-time RT-PCR and IgM capture ELISA.

    PubMed

    Mourya, Devendra T; Yadav, Pragya D; Mehla, Rajeev; Barde, Pradip V; Yergolkar, Prasanna N; Kumar, Sandeep R P; Thakare, Jyotsna P; Mishra, Akhilesh C

    2012-12-01

    Kyasanur forest disease (KFD) is a zoonotic viral disease caused by infection by a Flavivirus, a member of the family Flaviviridae. KFD is a public health concern in the Karnataka State in southern India. Available conventional diagnostic tests such as virus isolation and serological tests, such as haemagglutination inhibition and complement fixation tests are time consuming. This study reports the development of a nested RT-PCR [nRT-PCR] and a TaqMan-based real-time RT-PCR and IgM antibodies capture ELISA [MAC-ELISA] for rapid and accurate diagnosis of suspected KFD cases. The nRT-PCR and the TaqMan-based real-time RT-PCR assays were developed using gene sequences of the NS-5/non-coding region. Both the assays detected KFD viral RNA in acute phase human serum samples and can provide early diagnosis of infection. Real-time RT-PCR was found to be more sensitive than nRT-PCR, which could detect 38 copies of KFDV RNA. MAC-ELISA was developed for the detection of recent infections. Although real-time RT-PCR and nRT-PCR require expensive reagents, expensive equipment and trained personnel, the developed MAC-ELISA can be used easily in the affected areas. These tests add to the existing diagnosis arsenal against haemorrhagic viruses that are prevalent in India. These assays will also help to extend our knowledge of the pathology of KFD virus and its associated clinical features, by measuring the viral titre during infection and at the time of seroconversion. Information, which is not available currently because of the lack of appropriate diagnostic methods. In addition, early laboratory diagnosis of KFDV infection will help in the application of appropriate control measures and management of KFD cases.

  6. Multiple IgH Isotypes Including IgD, Subclasses of IgM, and IgY Are Expressed in the Common Ancestors of Modern Birds.

    PubMed

    Han, Binyue; Yuan, Hui; Wang, Tao; Li, Bo; Ma, Li; Yu, Shuyang; Huang, Tian; Li, Yan; Fang, Dongming; Chen, Xiaoli; Wang, Yongsi; Qiu, Si; Guo, Ying; Fei, Jing; Ren, Liming; Pan-Hammarström, Qiang; Hammarström, Lennart; Wang, Jun; Wang, Jian; Hou, Yong; Pan, Qingjie; Xu, Xun; Zhao, Yaofeng

    2016-06-15

    Although evolutionarily just as ancient as IgM, it has been thought for many years that IgD is not present in birds. Based on the recently sequenced genomes of 48 bird species as well as high-throughput transcriptome sequencing of immune-related tissues, we demonstrate in this work that the ostrich (Struthio camelus) possesses a functional δ gene that encodes a membrane-bound IgD H chain with seven CH domains. Furthermore, δ sequences were clearly identified in many other bird species, demonstrating that the δ gene is widely distributed among birds and is only absent in certain bird species. We also show that the ostrich possesses two μ genes (μ1, μ2) and two υ genes (υ1, υ2), in addition to the δ and α genes. Phylogenetic analyses suggest that subclass diversification of both the μ and υ genes occurred during the early stages of bird evolution, after their divergence from nonavian reptiles. Although the positions of the two υ genes are unknown, physical mapping showed that the remaining genes are organized in the order μ1-δ-α-μ2, with the α gene being inverted relative to the others. Together with previous studies, our data suggest that birds and nonavian reptile species most likely shared a common ancestral IgH gene locus containing a δ gene and an inverted α gene. The δ gene was then evolutionarily lost in selected birds, whereas the α gene lost in selected nonavian reptiles. The data obtained in this study provide significant insights into the understanding of IgH gene evolution in tetrapods.

  7. Genetic testing in ALS

    PubMed Central

    McLaughlin, Russell L.; Heverin, Mark; Thorpe, Owen; Abrahams, Sharon; Al-Chalabi, Ammar; Hardiman, Orla

    2017-01-01

    Objective: To determine the degree of consensus among clinicians on the clinical use of genetic testing in amyotrophic lateral sclerosis (ALS) and the factors that determine decision-making. Methods: ALS researchers worldwide were invited to participate in a detailed online survey to determine their attitudes and practices relating to genetic testing. Results: Responses from 167 clinicians from 21 different countries were analyzed. The majority of respondents (73.3%) do not consider that there is a consensus definition of familial ALS (FALS). Fifty-seven percent consider a family history of frontotemporal dementia and 48.5% the presence of a known ALS genetic mutation as sufficient for a diagnosis of FALS. Most respondents (90.2%) offer genetic testing to patients they define as having FALS and 49.4% to patients with sporadic ALS. Four main genes (SOD1, C9orf72, TARDBP, and FUS) are commonly tested. A total of 55.2% of respondents would seek genetic testing if they had personally received a diagnosis of ALS. Forty-two percent never offer presymptomatic testing to family members of patients with FALS. Responses varied between ALS specialists and nonspecialists and based on the number of new patients seen per year. Conclusions: There is a lack of consensus among clinicians as to the definition of FALS. Substantial variation exists in attitude and practices related to genetic testing of patients and presymptomatic testing of their relatives across geographic regions and between experienced specialists in ALS and nonspecialists. PMID:28159885

  8. Ventilatory Control in ALS

    PubMed Central

    Nichols, Nicole L.; Van Dyke, J.; Nashold, L.; Satriotomo, I.; Suzuki, M.; Mitchell, G.S.

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disease. ALS selectively causes degeneration in upper and lower (spinal) motor neurons, leading to muscle weakness, paralysis and death by ventilatory failure. Although ventilatory failure is generally the cause of death in ALS, little is known concerning the impact of this disorder on respiratory motor neurons, the consequences of respiratory motor neuron cell death, or the ability of the respiratory control system to “fight back” via mechanisms of compensatory respiratory plasticity. Here we review known effects of ALS on breathing, including possible effects on rhythm generation, respiratory motor neurons, and their target organs: the respiratory muscles. We consider evidence for spontaneous compensatory plasticity, preserving breathing well into disease progression despite dramatic loss of spinal respiratory motor neurons. Finally, we review current and potential therapeutic approaches directed toward preserving the capacity to breathe in ALS patients. PMID:23692930

  9. ALS2 mutations

    PubMed Central

    Schneider, Susanne A.; Carr, Lucinda; Deuschl, Guenther; Hopfner, Franziska; Stamelou, Maria; Wood, Nicholas W.; Bhatia, Kailash P.

    2014-01-01

    Objective: To determine the genetic etiology in 2 consanguineous families who presented a novel phenotype of autosomal recessive juvenile amyotrophic lateral sclerosis associated with generalized dystonia. Methods: A combination of homozygosity mapping and whole-exome sequencing in the first family and Sanger sequencing of candidate genes in the second family were used. Results: Both families were found to have homozygous loss-of-function mutations in the amyotrophic lateral sclerosis 2 (juvenile) (ALS2) gene. Conclusions: We report generalized dystonia and cerebellar signs in association with ALS2-related disease. We suggest that the ALS2 gene should be screened for mutations in patients who present with a similar phenotype. PMID:24562058

  10. Lou Gehrig's Disease (ALS)

    MedlinePlus

    ... when it becomes necessary. For instance, a power wheelchair can enable a paralyzed person with ALS to ... done these things despite being confined to a wheelchair for many years, being able to move only ...

  11. Genetic Testing for ALS

    MedlinePlus

    ... Involved Donate Familial Amyotrophic Lateral Sclerosis (FALS) and Genetic Testing By Deborah Hartzfeld, MS, CGC, Certified Genetic ... guarantee a person will develop symptoms of ALS. Genetic Counseling If there is more than one person ...

  12. Cosmic Galaxy-IGM HI Relation at z ∼ 2–3 Probed in the COSMOS/UltraVISTA 1.6 Deg2 Field

    NASA Astrophysics Data System (ADS)

    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< 23.4 and the Lyα forest absorption lines in the background quasar spectra selected from SDSS data with no signature of damped Lyα system contamination. We estimate a galaxy overdensity δ gal in an impact parameter of 2.5 (proper) Mpc, and calculate the Lyα forest fluctuations {δ }< F> whose negative values correspond to the strong Lyα forest absorption lines. We identify weak evidence of an anti-correlation between δ gal and {δ }< F> 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 }< F> ≃ 0.1(-0.4), three of which, B obs–D obs, significantly depart from the δ gal–{δ }< F> correlation, and weaken the correlation signal. We perform cosmological hydrodynamical simulations and compare with our observational results. Our simulations reproduce the δ gal–{δ }< F> 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.

  13. Ag-Al-Ca

    NASA Astrophysics Data System (ADS)

    Carow-Watamura, U.; Louzguine, D. V.; Takeuchi, A.

    This document is part of Part 1 http://dx.doi.org/10.1007/97.etType="URL"/> 'Systems from Ag-Al-Ca to Au-Pd-Si' of Subvolume B 'Physical Properties of Ternary Amorphous Alloys' of Volume 37 'Phase Diagrams and Physical Properties of Nonequilibrium Alloys' of Landolt-Börnstein - Group III 'Condensed Matter'. It contains the Chapter 'Ag-Al-Ca' with the content:

  14. [Immunological behavior (IgG, IgM, IgA) and total complement (CH50) of newborns infants with risk factors for early onset sepsis. Comparative analysis of newborns with and without infection].

    PubMed

    Ceccon, M E; Diníz, E M; Carneiro-Sampaio, M M; Arslanian, C; Diogo, C L; Ramos, J L; Vaz, F A

    1998-01-01

    Immunological behavior (IgG, IgM, IgA) and total Complement (CH50) of newborns infants with risk factors for early onset sepsis. Comparative analysis between newborns with and without infection. Rev. Hosp. Clín. Fac. Med. S. Paulo, 53(6): 303-310, 1998. The objective of this study was to verify the immunological behavior of the newborn infant in front of an infection. We studied 60 newborn infants that had risk factors for early onset sepsis (premature rupture membranes, clinic amnionitis or tract urinary infection) from de immunological and infection point of view. They were classified into three gestational age groups: < 34 weeks, between 34 and 36 6/7 weeks and > or = 37 weeks. Sepsis diagnosis was done through clinical and laboratorial data and we also included the followings exams: Immunological types (IgG, IgM, IgA) and total complement (CH50) obtained from the newborn at birth and on the fifth day of life. We could verify that 15 newborns (25%) presented early sepsis. There was a statistical association between perinatal asfixia and infection in the group with gestational age < 34 weeks and this same group presented statistical association between infection and death. The serical levels of IgG and CH50 were directly related to the gestational age and there were significant statistical differences between levels of IgG, IgM and total Complement between infected and not infected newborns within the same group os gestional age. We observed that the infection was associated to low levels of IgG and CH50, at birth and on the fifth day, mainly in the group of infected newborns with gestional age < 34 weeks, being this group, therefore, the one that would mostly benefit from an immunological support in front of and infection.

  15. 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.

    PubMed

    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.

  16. Complete sequence of the genes encoding the VH and VL regions of low- and high-affinity monoclonal IgM and lgA1 rheumatoid factors produced by CD5+ B cells from a rheumatoid arthritis patient

    PubMed Central

    Harindranath, Nagaradona; Goldfarb, Inna S.; Ikematsu, Hideyuki; Burastero, Samuele E.; Wilder, Ronald L.; Notkins, Abner L.; Casali, Paolo

    2015-01-01

    We have characterized the VH and VL genes of three low-affinity polyreactive and two high-affinlty monoreactive IgM and lgA1 rheumatoid factor (RF) mAb generated using circulating CD5+ B cells from a single rheumatoid arthritis patient. We found that four and one RF mAb utilized genes of the VHIV and VHIII families, respectively. The VHIV gene usage by these RF mAb differs from the preferential VHIII, VHI, and, to a lesser extent, VHII gene usage by the IgM with RF activity found In patients with mixed cryoglobulinemia, Waldenstrom's macroglobulinemia, and other monoclonal gammopathies. In addition, in contrast to the preponderant χL chain usage by the RF In these patients, a λL chain was utilized by all RF mAb from our rheumatoid arthritis patient. Two RF mAbs utilized VλI, two VλIV, and one VλIII L chains. The VH genes of the two low-affinity polyreactive IgM RF mAb were in germline configuration. When compared with the deduced amino acid sequence of the putatively corresponding genomic segment, the VH gene of the high-affinity monoreactive IgM RF mAb displayed five amino acid differences, all of which are in the complementarity determining regions (CDR), possibly the result of a process of somatic point mutation and clonal selection driven by Ag. The unavailability of the corresponding genomic VH segment sequences made it impossible to infer whether the VH genes utilized by the two lgA1 RF were in a germline or somatically mutated configuration. Sequencing of the genes encoding the H chain CDR3 (D segments) revealed that all three low-affinity polyreactive RF mAb displayed a much longer D segment (36–45 bases) than their high-affinity monoreactive counterparts (15–24 bases), raising the possibility that a long D segment may be one of the factors involved in antibody polyreactivity. PMID:1718404

  17. Statins: Do They Cause ALS?

    MedlinePlus

    Statins: Do they cause ALS? Do statins cause amyotrophic lateral sclerosis (ALS)? Answers from Francisco Lopez-Jimenez, M.D. ... D. References Sorensen HT, et al. Statins and amyotrophic lateral sclerosis: The level of evidence for an association. Journal ...

  18. Rapidly solidified NiAl and FeAl

    NASA Technical Reports Server (NTRS)

    Gaydosh, D. J.; Crimp, M. A.

    1984-01-01

    Melt spinning was used to produce rapidly solidified ribbons of the B2 intermetallics NiAl and FeAl. Both Fe-40Al and Fe-45Al possessed some bend ductility in the as spun condition. The bend ductility of Fe-40Al, Fe-45Al, and equiatomic NiAl increased with subsequent heat treatment. Heat treatment at approximately 0.85 T (sub m) resulted in significant grain growth in equiatomic FeAl and in all the NiAl compositions. Low bend ductility in both FeAl and NiAl generally coincided with intergranular failure, while increased bend ductility was characterized by increasing amounts of transgranular cleavage fracture.

  19. ALS superbend magnet system

    SciTech Connect

    Zbasnik, J.; Wang, S.T.; Chen, J.Y.; DeVries, G.J.; DeMarco, R.; Fahmie, M.; Geyer, A.; Green, M.A.; Harkins, J.; Henderson, T.; Hinkson, J.; Hoyer, E.H.; Krupnick, J.; Marks, S.; Ottens, F.; Paterson, J.A.; Pipersky, P.; Portmann, G.; Robin, D.A.; Schlueter, R.D.; Steier, C.; Taylor, C.E.; Wahrer, R.

    2000-09-15

    The Lawrence Berkeley National Laboratory is preparing to upgrade the Advanced Light Source (ALS) with three superconducting dipoles (Superbends). In this paper we present the final magnet system design which incorporates R&D test results and addresses the ALS operational concerns of alignment, availability, and economy. The design incorporates conduction-cooled Nb-Ti windings and HTS current leads, epoxy-glass suspension straps, and a Gifford-McMahon cryocooler to supply steady state refrigeration. We also present the current status of fabrication and testing.

  20. Fosetyl-al

    Integrated Risk Information System (IRIS)

    Fosetyl - al ; CASRN 39148 - 24 - 8 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Ef

  1. Al Shanker Remembers.

    ERIC Educational Resources Information Center

    American Educator, 2000

    2000-01-01

    In a 1996 interview shortly before his death, Al Shanker, longtime president of the American Federation of Teachers, discussed such topics as: his own educational experiences; how he learned about political fighting in the Boy Scouts; the appeal of socialism; multinational corporations and the nation state; teaching tough students; and John Dewey…

  2. Al Partitioning Patterns and Root Growth as Related to Al Sensitivity and Al Tolerance in Wheat.

    PubMed Central

    Samuels, T. D.; Kucukakyuz, K.; Rincon-Zachary, M.

    1997-01-01

    Studies of Al partitioning and accumulation and of the effect of Al on the growth of intact wheat (Triticum aestivum L.) roots of cultivars that show differential Al sensitivity were conducted. The effects of various Al concentrations on root growth and Al accumulation in the tissue were followed for 24 h. At low external Al concentrations, Al accumulation in the root tips was low and root growth was either unaffected or stimulated. Calculations based on regression analysis of growth and Al accumulation in the root tips predicted that 50% root growth inhibition in the Al-tolerant cv Atlas 66 would be attained when the Al concentrations were 105 [mu]M in the nutrient solution and 376.7 [mu]g Al g-1 dry weight in the tissue. In contrast, in the Al-sensitive cv Tam 105, 50% root growth inhibition would be attained when the Al concentrations were 11 [mu]M in the nutrient solution and 546.2 [mu]g Al g-1 dry weight in the tissue. The data support the hypotheses that differential Al sensitivity correlates with differential Al accumulation in the growing root tissue, and that mechanisms of Al tolerance may be based on strategies to exclude Al from the root meristems. PMID:12223623

  3. Al Sumelat Water Network. Village of Al Sumelat, Iraq

    DTIC Science & Technology

    2006-03-15

    OFFICE OF THE SPECIAL INSPECTOR GENERAL FOR IRAQ RECONSTRUCTION AL SUMELAT WATER NETWORK VILLAGE OF AL SUMELAT, IRAQ...Sumelat Water Network Village of Al Sumelat, Iraq 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e...Al Sumelat Water Network Village of Al Sumelat, Iraq Synopsis Introduction. This report was previously provided on a limited distribution basis

  4. Serum levels of immunoglobulins (IgG, IgA, IgM) in a general adult population and their relationship with alcohol consumption, smoking and common metabolic abnormalities

    PubMed Central

    Gonzalez-Quintela, A; Alende, R; Gude, F; Campos, J; Rey, J; Meijide, L M; Fernandez-Merino, C; Vidal, C

    2008-01-01

    The present study investigated serum immunoglobulin (Ig) concentrations in relation to demographic factors, common habits (alcohol consumption and smoking) and metabolic abnormalities in an adult population-based survey including 460 individuals. Serum levels of interleukin (IL)-6, a marker of inflammation, were also determined. After adjusting for confounders, male sex was associated positively with IgA levels and negatively with IgM levels. Age was associated positively with IgA and IgG levels. Smoking was associated negatively with IgG levels. Heavy drinking was associated positively with IgA levels. Metabolic abnormalities (obesity and metabolic syndrome) were associated positively with IgA levels. Abdominal obesity and hypertriglyceridaemia were the components of metabolic syndrome associated most strongly with serum IgA. Heavy drinkers with metabolic syndrome showed particularly high serum IgA levels. Serum IL-6 levels were correlated positively with IgA and IgG concentrations. It is concluded that sex, age, alcohol consumption, smoking and common metabolic abnormalities should be taken into account when interpreting serum levels of IgA, IgG and IgM. PMID:18005364

  5. Coxsackievirus B1-based antibody-capture enzyme-linked immunosorbent assay for detection of immunoglobulin G (IgG), IgM, and IgA with broad specificity for enteroviruses.

    PubMed Central

    Swanink, C M; Veenstra, L; Poort, Y A; Kaan, J A; Galama, J M

    1993-01-01

    An antibody-capture enzyme-linked immunosorbent assay (ELISA) with coxsackievirus B1 as the antigen was evaluated for detection of immunoglobulin G (IgG), IgM, and IgA antibodies and showed broad specificity for enteroviruses. In total, 116 serum or cerebrospinal fluid samples from 62 patients were tested by ELISA and the complement fixation test (CFT). Additionally, 15 serum samples that contained poliovirus-specific IgM antibody were tested. Serum samples from 200 healthy blood donors were used for standardization of the assays. The sensitivity of the ELISA varied with time of serum sampling, with a relatively low sensitivity when serum was collected within 3 days after the onset of symptoms (23%; 5 of 22) but good sensitivity when serum was collected later (83%; 20 of 24). The sensitivity was better than that of the CFT. The ELISAs were broadly reactive as concluded from typing of virus isolates that were simultaneously obtained. The assay did, furthermore, detect antibody against poliovirus type 3. Sera that contained rheumatoid factor, antinuclear antibody, or cardiolipin antibody (by the Venereal Disease Research Laboratory test) did not react in this ELISA. Nonspecific reactivity did occur, however, in cases of infectious mononucleosis and in Mycoplasma pneumoniae infection. The enterovirus-specific ELISA is found to be simple to perform, more sensitive than the CFT, and far less laborious than the neutralization test. PMID:8308117

  6. Precipitated immune complexes of IgM as well as of IgG can bind to rabbit polymorphonuclear leucocytes but only the immune complexes of IgG are readily phagocytosed.

    PubMed Central

    Furriel, R P; Lucisano, Y M; Mantovani, B

    1992-01-01

    We have shown by in vitro experiments, using immunofluorescence techniques, that precipitated immune complexes of IgM antibodies and ovalbumin (ICIgM) are able to bind to rabbit blood polymorphonuclear leucocytes (PMN), as well as immune complexes of IgG antibodies (ICIgG). This binding capacity for both classes of immune complexes is exhibited by more than 80% of the PMN cell population and is independent of Ca2+ in the medium. For ICIgG the binding to PMN can be completely inhibited by preincubation of the cells with soluble IgG used at physiological concentrations (competition for the Fc gamma receptors) while for ICIgM there is no such inhibition by fluid-phase IgM. After binding to the leucocytes there was a striking difference in the fate of ICIgM and ICIgG: whereas the ICIgG was readily phagocytosed (endocytosed), the ICIgM remained mostly on the cell surface, being only poorly endocytosed after 1 hr incubation at 37 degrees. This was demonstrated by a quantitative fluorimetric method developed to assay phagocytosis of immune complexes, and was confirmed by a qualitative fluorescence quenching technique. These results may have implications for understanding the fate of these classes of immune complexes formed in circulation or deposited in tissues, and the participation of PMN in inflammatory reactions and tissue injury in immune complex diseases. Images Figure 3 PMID:1572698

  7. A Prospective Assessment of the Accuracy of Commercial IgM ELISAs in Diagnosis of Japanese Encephalitis Virus Infections in Patients with Suspected Central Nervous System Infections in Laos

    PubMed Central

    Moore, Catrin E.; Blacksell, Stuart D.; Taojaikong, Thaksinaporn; Jarman, Richard G.; Gibbons, Robert V.; Lee, Sue J.; Chansamouth, Vilada; Thongpaseuth, Soulignasack; Mayxay, Mayfong; Newton, Paul N.

    2012-01-01

    Japanese encephalitis virus (JEV) is a major cause of encephalitis in Asia. We estimated the diagnostic accuracy of two anti-JEV immunoglobulin M (IgM) enzyme-linked immunosorbent assays (ELISAs) (Panbio and XCyton JEVCheX) compared with a reference standard (AFRIMS JEV MAC ELISA) in a prospective study of the causes of central nervous system infections in Laos. Cerebrospinal fluid (CSF; 515 patients) and serum samples (182 patients) from those admitted to Mahosot Hospital, Vientiane, were tested. The CSF from 14.5% of acute encephalitis syndrome (AES) patients and 10.1% from those with AES and meningitis were positive for anti-JEV IgM in the reference ELISA. The sensitivities for CSF were 65.4% (95% confidence interval [CI] = 51–78) (Xcyton), 69.2% (95% CI = 55–81) (Panbio), however 96.2% (95% CI = 87–100) with Panbio Ravi criteria. Specificities were 89–100%. For admission sera from AES patients, sensitivities and specificities of the Panbio ELISA were 85.7% (95% CI = 42–100%) and 92.9% (95% CI = 83–98%), respectively. PMID:22764310

  8. ALS insertion devices

    NASA Astrophysics Data System (ADS)

    Hoyer, E.; Chin, J.; Halbach, K.; Hassenzahl, W. V.; Humphries, D.; Kincaid, B.; Lancaster, H.; Plate, D.

    1991-08-01

    The Advanced Light Source (ALS), the first US third generation synchrotron radiation source, is currently under construction at the Lawrence Berkeley Laboratory. The low-emittance, 1.5 GeV electron storage ring and the insertion devices are specifically designed to produce high brightness beams in the UV to soft X-Ray range. The planned initial complement of insertion devices includes four 4.6 m long undulators, with period lengths of 3.9 cm, 5.0 cm (2) and 8.0 cm, and a 2.9 m long wiggler of 16 cm period length. Undulator design is well advanced and fabrication has begun on the 5.0 cm and 8.0 cm period length undulators. This paper discusses ALS insertion device requirements; general design philosophy; and design of the magnetic structure, support structure/drive systems, control system and vacuum system.

  9. Frequently Asked Questions about ALS and the ALS Registry

    MedlinePlus

    ... Why is it necessary to provide my Social Security Number (SSN) when registering in the National ALS ... Why is it necessary to provide my Social Security Number (SSN) when registering in the National ALS ...

  10. Cryptosporidium parvum in calves: kinetics and immunoblot analysis of specific serum and local antibody responses (immunoglobulin A [IgA], IgG, and IgM) after natural and experimental infections.

    PubMed Central

    Peeters, J E; Villacorta, I; Vanopdenbosch, E; Vandergheynst, D; Naciri, M; Ares-Mazás, E; Yvoré, P

    1992-01-01

    Fecal and serum anti-Cryptosporidium parvum immunoglobulin A (IgA), IgM, and IgG were monitored by an enzyme-linked immunosorbent assay after experimental and natural infection of calves with C. parvum. Although all experimentally infected calves showed high levels of colostral antibodies in the feces, they acquired C. parvum infection. Three of five animals died. Calves which acquired natural infection showed only diarrhea. Levels of colostral coproantibodies dropped quickly. Experimental infection was followed by a rise in local anti-C. parvum IgM levels from day 5 postinfection (p.i.). IgM peaked at day 14 p.i. and then disappeared quickly. Anti-C. parvum IgA levels rose between days 7 and 14 p.i. and decreased slowly. Rising levels of coproantibodies coincided with falling oocyst output. Fecal anti-C. parvum IgG levels rose slightly during oocyst output, and IgG disappeared 3 weeks p.i. Similar kinetics were established in naturally infected calves. Although fecal anti-C. parvum IgA levels declined slowly, reinfections were established 5, 7, and 14 weeks after the primary contact. Serum anti-C. parvum IgG levels rose during maximal oocyst excretion, whereas serum anti-C. parvum IgA levels peaked later than did local IgA levels. Challenge reinfection of naturally infected calves at day 112 was not followed by clinical signs or oocyst output or by a secondary antibody response. Sequential Western immunoblotting with fecal extracts revealed up to 32 different parasite antigens. Convalescent-phase sera recognized up to 23 antigens. Fecal IgA reacted intensely with antigens with relative molecular weights (M(r)) of approximately 11,000 and 15,000. These antigens were not recognized by convalescent-phase serum IgG. Both local IgA and serum IgG also showed strong reactions with 23,000- and 44,000-M(r) antigens and with several antigens of between 66,200 and 200,000 M(r). Most bands remained detectable for at least 16 weeks p.i. Images PMID:1587597

  11. Two years' performance of an in-house ELISA for diagnosis of Legionnaires' disease: detection of specific IgM and IgG antibodies against Legionella pneumophila serogroup 1, 3 and 6 in human serum.

    PubMed

    Elverdal, P L; Jørgensen, C S; Krogfelt, K A; Uldum, S A

    2013-08-01

    The aim of this study was to evaluate the performance of an in-house ELISA for the diagnosis of Legionnaires' disease (LD) by detection of IgM and IgG antibodies against Legionella (L.) pneumophila serogroups (sg) 1, 3 and 6. The evaluation was done throughout a two-year period in a diagnostic routine laboratory. Furthermore, the sensitivity of four different methods, the in-house L. pneumophila antibody test (ELISA), the urinary antigen test (Binax® EIA), an in-house PCR and culture, both alone and in combination was evaluated. From 2008 to 2010, 12,158 serum samples from 10,503 patients were analysed. During the same period, 361 cases of laboratory-confirmed LD cases were recorded in Denmark, but of these only 113 had a serum sample examined. The positive predictive value of the in-house ELISA was calculated to be 12.8 and the negative predictive value was 99.6, using only the confirmed LD cases as true positives. The sensitivity of the in-house ELISA for the detection of IgM and IgG antibodies in the confirmed LD cases was 61% and 36%, respectively. By combining the two ELISA assays the sensitivity increased to 66%. The sensitivity of the Legionella urinary antigen test (Binax® EIA) was 63%, of the in-house PCR 87% and of culture 69%. When all the different methods were combined, a higher sensitivity was calculated--for in-house ELISA (IgM+IgG) and Binax® EIA 91%, in-house ELISA (IgM+IgG) and in-house PCR 93%, in-house ELISA (IgM+IgG) and culture 93%, Binax® EIA and in-house PCR 79%, Binax® EIA and culture 68% and in-house PCR and culture 94%. This study confirms that the detection of IgG and IgM antibodies by ELISA is an important diagnostic tool, also during the initial phase of the disease. Furthermore, we showed that LD in Denmark with or without serum samples collected exhibits the same age and sex distribution and epidemiology, as in the rest of Europe, i.e., mostly men are infected, infections are mostly community acquired, followed by infection from

  12. Clonal analysis of a human antibody response. Quantitation of precursors of antibody-producing cells and generation and characterization of monoclonal IgM, IgG, and IgA to rabies virus

    PubMed Central

    1990-01-01

    We quantitated and characterized the changes in the human B cell repertoire, at the clonal level, before and after immunization with rabies virus. Moreover, we generated 10 monoclonal cell lines producing IgM, IgG, and IgA antibodies to the virus. We found that in healthy subjects, not previously exposed to the virus, nearly 2% of the circulating B lymphocytes were committed to the production of antibodies that bound the virus. These B cells expressed the surface CD5 molecule. The antibodies they produced were polyreactive IgM that displayed a relatively low affinity for the virus components (Kd, 1.0- 2.4 x 10(-6) g/microliters). After immunization, different anti-virus (IgG and IgA) antibody-producing cells consistently appeared in the circulation and increased from less than 0.005% to greater than 10% of the total B cells committed to the production of IgG and IgA, respectively. Most of such B cells do not express CD5 and produce monoreactive antibodies of high affinity for rabies virus (Kd, 6.5 x 10(-9) to 1.2 x 10(-10) g/microliters). One of these IgG mAbs efficiently neutralized rabies virus in vitro and in vivo, as detailed elsewhere (Dietzschold, B., P. Casali, Y. Ueki, M. Gore, C. E. Rupprecht, A. L. Notkins, and H. Koprowski, manuscript submitted for publication). Hybridization experiments using probes specific for the different human V gene segment families revealed that cell precursors producing low affinity IgM binding to rabies virus utilized a restricted number of VH gene segments (i.e., only members of the VHIIIb subfamily), whereas cell precursors producing high affinity IgG and IgA to rabies virus utilized an assortment of different VH gene segments (i.e., members of the VHI, VHIII, VHIV, and VHVI families and VHIIIb subfamily). In conclusion, our studies show that EBV transformation in conjunction with limiting dilution technology and somatic cell hybridization techniques are useful methods for quantitating, at the B cell clonal level, the human

  13. Al Jazirah, Sudan

    NASA Technical Reports Server (NTRS)

    2008-01-01

    Al Jazirah (also Gezira) is one of the 26 states of Sudan. The state lies between the Blue Nile and the White Nile in the east-central region of the country. It is a well populated area suitable for agriculture. The area was at the southern end of Nubia and little is known about its ancient history and only limited archaeological work has been conducted in this area. The region has benefited from the Gezira Scheme, a program to foster cotton farming begun in 1925. At that time the Sennar Dam and numerous irrigation canals were built. Al Jazirah became the Sudan's major agricultural region with more than 2.5 million acres (10,000 km) under cultivation. The initial development project was semi-private, but the government nationalized it in 1950. Cotton production increased in the 1970s but by the 1990s increased wheat production has supplanted a third of the land formerly seeded with cotton.

    The image was acquired December 25, 2006, covers an area of 56 x 36.4 km, and is located near 14.5 degrees north latitude, 33.1 degrees east longitude.

    The U.S. science team is located at NASA's Jet Propulsion Laboratory, Pasadena, Calif. The Terra mission is part of NASA's Science Mission Directorate.

  14. AL Amyloidosis and Agent Orange

    MedlinePlus

    ... for survivors' benefits . Research on AL amyloidosis and herbicides The Health and Medicine Division (formally known as ... to the compounds of interest found in the herbicide Agent Orange and AL amyloidosis." VA made a ...

  15. Al Qaeda as a System

    DTIC Science & Technology

    2006-03-15

    either as welcome guests or parasites . As welcome guests, Al Qaeda members take sanctuary in sponsor states. Sponsor states provide Al Qaeda with...sponsorship, Al Qaeda takes sanctuary as parasites either overtly or covertly. They take overt sanctuary in countries that publicly claim a policy...39 Yehudit Barsky, “Al Qa’ida, Iran, and Hezbollah: A Continuing Symbiosis ,” The American Jewish Committee Series on Terrorism , February 2004, 2-3

  16. Development of an indirect ELISA method for the parallel measurement of IgG and IgM antibodies against Crimean-Congo haemorrhagic fever (CCHF) virus using recombinant nucleoprotein as antigen.

    PubMed

    Dowall, S D; Richards, K S; Graham, V A; Chamberlain, J; Hewson, R

    2012-02-01

    Recombinant nucleoprotein from Crimean-Congo Haemorrhagic Fever (CCHF) virus was successfully derived from a baculovirus expression system and purified for use in a novel enzyme-linked immunosorbent assay (ELISA) diagnostic test. Comparable tests were used for detection of IgG and IgM antibodies, thus allowing efficient detection of both antibodies in parallel. The major benefits of the assay also included removing any requirement for polyclonal sera, thus eliminating variation in preparations and allowing standardisation between laboratories. The assay was successfully tested using a panel of positive sera supplied from samples identified as being positive in Turkey, Tajikistan and Kosovo and shown to be sensitive and specific. It is envisaged that this simple diagnostic ELISA for CCHF virus infection which removes the reliance on polyclonal antibody preparations, will be accessible to a wider range of laboratories enabling them to carry out routine diagnosis. This will improve the efficiency of diagnosis and subsequent management of infected patients.

  17. F(ab')2 fragment of a gp41 NHR-trimer-induced IgM monoclonal antibody neutralizes HIV-1 infection and blocks viral fusion by targeting the conserved gp41 pocket.

    PubMed

    Lu, Lu; Wei, Meili; Chen, Yanxia; Xiong, Weiliang; Yu, Fei; Qi, Zhi; Jiang, Shibo; Pan, Chungen

    2013-11-01

    Using a recombinant protein N46FdFc that mimics the HIV-1 gp41 N-helix trimer to immunize mice, we identified the first IgM monoclonal antibody 18D3 that specifically bound to the conserved gp41 pocket. Its F(ab')2 fragment potently inhibited HIV-1 Env-mediated cell-cell fusion and neutralized infection by laboratory-adapted and primary HIV-1 isolates with different subtypes and tropism, including the T20-resistant variants. This F(ab')2 fragment can be used to develop a bispecific broad neutralizing monoclonal antibody or HIV-1 inactivator as a novel immunotherapeutic for treatment and prevention of HIV-1 infection.

  18. Early neonatal diagnosis of congenital toxoplasmosis: value of comparative enzyme-linked immunofiltration assay immunological profiles and anti-Toxoplasma gondii immunoglobulin M (IgM) or IgA immunocapture and implications for postnatal therapeutic strategies.

    PubMed Central

    Pinon, J M; Chemla, C; Villena, I; Foudrinier, F; Aubert, D; Puygauthier-Toubas, D; Leroux, B; Dupouy, D; Quereux, C; Talmud, M; Trenque, T; Potron, G; Pluot, M; Remy, G; Bonhomme, A

    1996-01-01

    Diagnostic strategies for congenital toxoplasmosis have changed profoundly in recent years. Immunological diagnostic methods, long considered disappointing, can now be used at a very early stage. Over a 3-year period, 1,050 infants at risk of congenital toxoplasmosis (born to 1,048 mothers infected during pregnancy) were monitored for a minimum of 12 months and a maximum of 7 years. More than 6,000 serum specimens were analyzed by comparative mother-infant immunological profiles (CIPs) based on an enzyme-linked immunofiltration assay (ELIFA) and an immunocapture method for the detection of specific immunoglobulin M (IgM) and IgA. IgG antibodies were also titrated. One hundred three cases of congenital toxoplasmosis were demonstrated. The CIP-ELIFA method had a better diagnostic yield (sensitivity, 90%) than specific IgM and/or IgA detection by immunocapture assay (sensitivity, 77%). By using a combination of these tests, congenital infection was diagnosed in the first month and the first 3 months of life in 90 and 94% of infants with toxoplasmosis, respectively, with a specificity of 99.8% and a positive predictive value of 99% at 8 months of age. This dual diagnostic approach (ELIFA and IgM-IgA immunocapture) is highly efficient and has important implications for therapy. Indeed, early postnatal diagnosis based on objective evidence enables therapy with pyrimethamine-sulfadoxine to be started immediately for 24 months, while spiramycin (which used to be given preventively for 9 to 12 months to all infants at risk) can be stopped after the first 3 months of life. PMID:8904418

  19. 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

    PubMed Central

    Lopez-Saucedo, Catalina; Bernal-Reynaga, Rodolfo; Zayas-Jahuey, Jesus; Galindo-Gomez, Silvia; Shibayama, Mineko; Garcia-Galvez, Carlos; Estrada-Parra, Sergio; Estrada-Garcia, Teresa

    2015-01-01

    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. PMID:26064940

  20. Growth and Optical Properties of Al rich AlN/AlGaN Quantum Wells

    NASA Astrophysics Data System (ADS)

    Tahtamouni, T. M. Al; Nepal, N.; Nakarmi, M. L.; Lin, J. Y.; Jiang, H. X.

    2006-03-01

    Al rich AlGaN alloys are promising materials for the applications in the optoelectronic devices such as deep ultraviolet (UV) emitters and detectors in the spectral range down to 200 nm. AlGaN based UV emitters (λ<340nm) has applications in bio-chemical agent detection and medical research/ health care. To realize deep UV emission (λ< 280 nm) Al rich AlGaN based quantum wells (QWs) are required. We report here the growth of AlN/AlxGa1-xNQWs (x>0.65) on AlN/sapphire templates by metalorganic chemical vapor deposition (MOCVD). Deep UV photoluminescence (PL) was employed to study the optical properties of the QWs. Well width (Al composition) dependence was studied by varying the QW thickness (Al composition) with fixed x ˜ 0.65 (well width at 3 nm). Optical properties of these QWs such as the effects of alloy fluctuation, temperature, strain and piezoelectric field, carrier and exciton localizations on the quantum efficiency have been studied. Carrier and exciton dynamics were probed. Implications of our findings on the applications of Al rich AlN/AlGaN QWs for UV emitters and detectors will also be discussed.

  1. Studies of 27Al NMR in SrAl4

    NASA Astrophysics Data System (ADS)

    Niki, Haruo; Higa, Nonoka; Kuroshima, Hiroko; Toji, Tatsuki; Morishima, Mach; Minei, Motofumi; Yogi, Mamoru; Nakamura, Ai; Hedo, Masato; Nakama, Takao; Ōnuki, Yoshichika; Harima, Hisatomo

    A charge density wave (CDW) transition at TCDW = 243 K and a structural phase (SP) transition at approximately 100 K occur in SrAl4 with the BaAl4-type body center tetragonal structure, which is the divalent and non-4f electron reference compound of EuAl4. To understand the behaviors of the CDW and SP transitions, the 27Al NMR measurements using a single crystal and a powder sample of SrAl4 have been carried out. The line width below TCDW is modulated by an electrical quadruple interaction between 27Al nucleus and CDW charge modulation. The incommensurate CDW state below TCDW changes into a different structure below TSP. The temperature dependences of Knight shifts of 27Al(I) and 27Al(II) show the different behaviors. The temperature variation of 27Al(I) Knight shift shows anomalies at the CDW and SP transition temperatures, revealing the shift to negative side below TCDW, which is attributable to the core polarization of the d-electrons. However, 27Al(II) Knight shift keeps almost constant except for the small shift due to the SP transition. The 1/T1T of 27Al(I) indicates the obvious changes due to the CDW and SP transitions, while that of 27Al(II) takes a constant value. The density of state at the Fermi level at Al(I) site below 60 K would be about 0.9 times less than that above TCDW.

  2. Rub' al Khali, Arabia

    NASA Technical Reports Server (NTRS)

    2008-01-01

    The Rub' al Khali is one of the largest sand deserts in the world, encompassing most of the southern third of the Arabian Peninsula. It includes parts of Oman, United Arab Emirates, and Yemen. The desert covers 650,000 square kilometers, more than the area of France. Largely unexplored until recently, the desert is 1000 km long and 500 km wide. The first documented journeys made by Westerners were those of Bertram Thomas in 1931 and St. John Philby in 1932. With daytime temperatures reaching 55 degrees Celsius, and dunes taller than 330 meters, the desert may be one of the most forbidding places on Earth.

    The image was acquired December 2, 2005, covers an area of 54.8 x 61.9 km, and is located near 20.7 degrees north latitude, 53.6 degrees east longitude.

    The U.S. science team is located at NASA's Jet Propulsion Laboratory, Pasadena, Calif. The Terra mission is part of NASA's Science Mission Directorate.

  3. Morton et al. Reply

    NASA Technical Reports Server (NTRS)

    Morton, Douglas C.; Nagol, Jyoteshwar; Carabajal, Claudia C.; Rosette, Jacqueline; Palace, Michael; Cook, Bruce D.; Vermote, Eric F.; Harding, David J.; North, Peter R. J.

    2016-01-01

    Multiple mechanisms could lead to up-regulation of dry-season photosynthesis in Amazon forests, including canopy phenology and illumination geometry. We specifically tested two mechanisms for phenology-driven changes in Amazon forests during dry-season months, and the combined evidence from passive optical and lidar satellite data was incompatible with large net changes in canopy leaf area or leaf reflectance suggested by previous studies. We therefore hypothesized that seasonal changes in the fraction of sunlit and shaded canopies, one aspect of bidirectional reflectance effects in Moderate Resolution Imaging Spectroradiometer (MODIS) data, could alter light availability for dry-season photosynthesis and the photosynthetic capacity of Amazon forests without large net changes in canopy composition. Subsequent work supports the hypothesis that seasonal changes in illumination geometry and diffuse light regulate light saturation in Amazon forests. These studies clarify the physical mechanisms that govern light availability in Amazon forests from seasonal variability in direct and diffuse illumination. Previously, in the debate over light limitation of Amazon forest productivity, seasonal changes in the distribution of light within complex Amazon forest canopies were confounded with dry-season increases in total incoming photosynthetically active radiation. In the accompanying Comment, Saleska et al. do not fully account for this confounding effect of forest structure on photosynthetic capacity.

  4. Alexandria (Al Iskandariya), Egypt

    NASA Technical Reports Server (NTRS)

    2002-01-01

    This image of Alexandria was taken by astronauts on board the International Space Station in December 2000 using an Electronic Still Camera. A wider-angle view (STS088-739-90) taken from the Space Shuttle in December 1998 is available for context. Alexandria (Al Iskandariya) occupies a T-shaped peninsula and strip of land separating the Mediterranean from Lake Mariout. Originally the town was built upon a mole (stone breakwater) called Heptastadium, which joined the island of Pharos (see referenced website, below) to the mainland. Since then sedimentary deposits have widened the mole. Since 1905, when the 370,000 Alexandrians lived in an area of about 4 sq km between the two harbors, the city (population 4 million; see referenced website, below) has grown beyond its medieval walls and now occupies an area of about 300 sq km. The Mahmudiya Canal, connecting Alexandria with the Nile, runs to the south of the city and, by a series of locks, enters the harbor of the principal port of Egypt (note ships). The reddish and ochre polygons west of Lake Mariout are salt-evaporation, chemical-storage, and water-treatment ponds within the coastal lagoon. Reference Youssef Halim and Fatma Abou Shouk, 2000, Human impacts on Alexandria's marine environment: UNESCO, Coastal Regions and Small Islands Unit (CSI), Coastal Management Sourcebooks 2 (accessed December 20, 2000) Additional photographs taken by astronauts can be viewed at NASA-JSC's Gateway to Astronaut Photography of Earth. Image ISS001-ESC-5025 provided by the Earth Sciences and Image Analysis Laboratory, Johnson Space Center.

  5. Is there a paraneoplastic ALS?

    PubMed

    Corcia, Philippe; Gordon, Paul H; Camdessanche, Jean-Philippe

    2015-06-01

    Our objective was to examine the strength of evidence in support of the paraneoplastic syndrome (PNS) as one cause of ALS and, if the association appears more likely than chance, determine which features of ALS imply concurrent malignancy. We reviewed the literature on concurrent ALS and neoplasia assessing the strength of evidence for the association. Most accounts of ALS and neoplasm are case reports or small uncontrolled series. In order of strength of evidence, three clinical situations that support a paraneoplastic aetiology for ALS are: 1) laboratory evidence of well-characterized onconeuronal antibodies, most often anti-Hu, anti-Yo or anti-Ri; 2) co-occurrence of ALS and a neoplasm known to cause PNS, usually lymphoma or cancer of the breast; and 3) combined ALS and a neoplasm not classically associated with PNS, without detectable onconeuronal antibodies. Clinical features that warrant evaluation of neoplasm include upper motor neuron disease in elderly females, rapid progression, non-motor signs, and young onset. In conclusion, most examples of ALS and neoplasm do not constitute a classically established PNS. Rare instances of elevated onconeuronal antibody titres or typical neoplasm, implies that, albeit rare, the PNS is one of a multitude of causes of ALS.

  6. Impurity Enhancement of Al_2O_3/Al Adhesion

    NASA Astrophysics Data System (ADS)

    Wang, Xiao-Gang; Smith, John R.; Zhang, Wenqing; Evans, Anthony

    2003-03-01

    Our first-principles computations indicate that the clean Al_2O_3/Al interface is relatively weak - weaker than bulk Al. Fracture experiments reveal that the interface is relatively strong with observed failure in bulk Al, however. This paradox is resolved via doping effects of the common impurity C. We have found that only 1/3 of a monolayer of carbon segregated to the interface can increase the work of separation by a factor of 3. The resulting strong interface is consistent with fracture experiments. It arises due to void formation in the interface, which provides low-strain sites for the carbon to segregate to. The degree of void formation is consistent with the relatively high heat of oxide formation of Al.

  7. Thermal Modeling of Al-Al and Al-Steel Friction Stir Spot Welding

    NASA Astrophysics Data System (ADS)

    Jedrasiak, P.; Shercliff, H. R.; Reilly, A.; McShane, G. J.; Chen, Y. C.; Wang, L.; Robson, J.; Prangnell, P.

    2016-09-01

    This paper presents a finite element thermal model for similar and dissimilar alloy friction stir spot welding (FSSW). The model is calibrated and validated using instrumented lap joints in Al-Al and Al-Fe automotive sheet alloys. The model successfully predicts the thermal histories for a range of process conditions. The resulting temperature histories are used to predict the growth of intermetallic phases at the interface in Al-Fe welds. Temperature predictions were used to study the evolution of hardness of a precipitation-hardened aluminum alloy during post-weld aging after FSSW.

  8. Intestinal IgA⁺ cell numbers as well as IgA, IgG, and IgM contents correlate with mucosal humoral immunity of broilers during supplementation with high fluorine in the diets.

    PubMed

    Luo, Qin; Cui, Hengmin; Peng, Xi; Fang, Jing; Zuo, Zhicai; Deng, Junliang; Liu, Juan; Deng, Yubing

    2013-07-01

    Fluoride (F), a well-recognized harmful substance, is easily absorbed by the intestinal mucosa. The intestinal mucosal immune system is equipped with unique innate and adaptive defense mechanisms that provide a first line of protection against infectious agents. Meanwhile, immunoglobulins are the major secretory products of the adaptive immune system and their levels can be a strong indicator of a disease or condition. In this study, therefore, we investigated the effects of high dietary fluorine on the numbers of immunoglobulin A-positive (IgA(+)) cells in the lamina propria of intestines (duodenum, jejunum and ileum) by immunohistochemistry as well as on the contents of immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) in the mucosa of intestines (duodenum, jejunum, and ileum) by enzyme-linked immunosorbent assay (ELISA). A total of 280 1-day-old healthy avian broilers were randomly divided into four groups and fed on a corn-soybean basal diet as control diet (fluorine 22.6 mg/kg) or the same basal diet supplemented with 400, 800, and 1,200 mg/kg fluorine (high fluorine groups I, II, and III) in the form of sodium fluoride (NaF) for 42 days. The experimental data showed that the numbers of IgA(+) cells as well as the IgA, IgG, and IgM contents were significantly decreased (P < 0.01 or P < 0.05) in the high fluorine groups II and III when compared with those of the control group. It was concluded that dietary fluorine in the range of 800-1,200 mg/kg significantly reduced the numbers of the IgA(+) cells and the contents of aforementioned immunoglobulins in the intestines (duodenum, jejunum, and ileum) of broilers, which could finally impact the mucosal humoral immune function in the intestines by a way that reduces the lymphocyte population and/or lymphocyte activation.

  9. Philosophieren als Unterrichtsprinzip im Mathematikunterricht

    NASA Astrophysics Data System (ADS)

    Meerwaldt, Diana

    Philosophieren und Mathematik scheinen zunächst gegensätzliche Bereiche zu sein, die sich kaum vereinbaren lassen. Dies trifft für eine Auffassung zu, die Philosophieren als "Gerede" disqualifiziert und Mathematik als eine reine "Formelwissenschaft" begreift. Beide Auffassungen werden den Gegenständen nicht gerecht.

  10. The Evolution of Al Qaeda

    DTIC Science & Technology

    2007-06-15

    Al Qaeda is a product of the forces of globalization. Increasing access to global finances , international travel, and sophisticated technology is...evolution. Al Qaeda is a product of the forces of globalization. Increasing access to global finances , international travel, and sophisticated technology...75 Finance

  11. Characteristics of CeCoIn5/Al/AlOx/Nb and CeCoIn5/Al/AlOx/Al Tunnel Junctions

    SciTech Connect

    Petrovic, C.; Nevirkovets, I.P.; Chernyashevskyy, O.; Hu, R.; Ketterson, J.B.; Sarma, B.K.

    2009-03-03

    We report characteristics of CeCoIn{sub 5}/Al/AlO{sub x}/Nb and CeCoIn{sub 5}/Al/AlO{sub x}/Al tunnel junctions fabricated on the (0 0 1) surface of CeCoIn{sub 5} crystal platelets. The main result of this work is the observation of a low Josephson current (as compared with that expected from the Ambegaokar-Baratoff formula), which is consistent with idea that the order parameter in the heavy-fermion superconductor CeCoIn{sub 5} has unconventional pairing symmetry.

  12. [Detection of anti-Toxoplasma gondii IgG, IgM and IgA immunoglobulins in the serum, cerebrospinal fluid and saliva of patients with acquired immunodeficiency syndrome and neurotoxoplasmosis].

    PubMed

    Borges, Aercio Sebastião; Figueiredo, José Fernando de Castro

    2004-12-01

    We studied 55 patients with acquired immunodeficiency syndrome (AIDS) and neurotoxoplasmosis (group 1), 37 patients with AIDS and neurological involvement due to another etiology (group 2) and 18 anti-HIV-negative individuals with neurological manifestations, by searching for anti-T. gondii IgG, IgA and IgM immunoglobulins in serum, cerebrospinal fluid (CSF)and saliva, using ELISA. The negative predictive value of the test for IgG in serum was 100% and in CSF, 92.4%. There was no difference among the three groups studied regarding IgA in serum. For IgA, in CSF the test reached 72.7% specificity (p<0.05). In saliva, only the detection of IgG was found to be correlated with a diagnosis of neurotoxoplasmosis. We emphasize that the absence of anti-T. gondii IgG antibodies in serum and CSF strongly indicates the absence of a diagnosis of neurotoxoplasmosis and that specific IgA immunoglobulins in CSF and IgG in saliva may represent two auxiliary markers for the differential diagnosis of toxoplasmic encephalitis in AIDS.

  13. Medical application of 26Al

    NASA Astrophysics Data System (ADS)

    Steinhausen, C.; Gerisch, P.; Heisinger, B.; Hohl, Ch.; Kislinger, G.; Korschinek, G.; Niedermayer, M.; Nolte, E.; Dumitru, M.; Alvarez-Brückmann, M.; Schneider, M.; Ittel, T. H.

    1996-06-01

    Accelerator mass spectrometry (AMS) measurements with 26Al as tracer were performed in order to study the aluminium metabolism and anomalies in the human body and in rats. In particular, the differences between healthy volunteers and patients with renal failure were investigated. The obtained data points of 26Al in blood and urine were described by an open compartment model with three peripheral compartments. It was found that the minimum of peripheral compartments needed to describe 26Al concentrations in blood and urine over a time period of three years is at least three.

  14. Reply to Gopalswamy et al.

    NASA Technical Reports Server (NTRS)

    Cane, H. V.; Richardson, I. G.

    2003-01-01

    The comment of Gopalswamy et al. (thereafter GMY) relates to a letter discussing coronal mass ejections (CMEs), interplanetary ejecta and geomagnetic storms. GMY contend that Cane et al. incorrectly identified ejecta (interplanetary CMEs) and hypothesize that this is because Cane et al. fail to understand how to separate ejecta from "shock sheaths" when interpreting solar wind and energetic particle data sets. They (GMY) are wrong be cause the relevant section of the paper was concerned with the propagation time to 1 AU of any potentially geoeffective structures caused by CMEs, i.e. upstream compression regions with or without shocks, or ejecta. In other words, the travel times used by Cane et al. were purposefully and deliberately distinct from ejecta travel times (except for those slow ejecta, approx. 30% of their events, which generated no upstream features), and no error in identification was involved. The confusion of GMY stems from the description did not characterize the observations sufficiently clearly.

  15. In memory of Al Cameron

    NASA Astrophysics Data System (ADS)

    Cowan, John; Truran, James W.

    Al Cameron, who died recently (October 3, 2005) at 80, was one of the giants in astrophysics. His insights were profound and his interests were wide-ranging. Originally trained as a nuclear physicist, he made major contributions in a number of fields, including nuclear reactions in stars, nucleosynthesis, the abundances of the elements in the Solar System, and the origin of the Solar System and the Moon. In 1957, Cameron and, independently, Burbidge, Burbidge, Fowler and Hoyle, wrote seminal papers on nuclear astrophysics. Most of our current ideas concerning ele- ment formation in stars have followed from those two pioneering and historical works. Al also made many contributions in the field of Solar System physics. Particularly noteworthy in this regard was Cameron's work on the formation of the Moon. Al was also a good friend and mentor of young people. Al Cameron will be missed by many in the community both for his scientific contributions and for his friendship.

  16. Al-Co-Fe (030)

    NASA Astrophysics Data System (ADS)

    Carow-Watamura, U.; Louzguine, D. V.; Takeuchi, A.

    This document is part of Part 1 http://dx.doi.org/10.1007/9getType="URL"/> 'Systems from Ag-Al-Ca to Au-Pd-Si' of Subvolume B 'Physical Properties of Ternary Amorphous Alloys' of Volume 37 'Phase Diagrams and Physical Properties of Nonequilibrium Alloys' of Landolt-Börnstein - Group III 'Condensed Matter'. It contains the Chapter 'Al-Co-Fe (030)' with the content:

  17. Al-La-Nb (068)

    NASA Astrophysics Data System (ADS)

    Carow-Watamura, U.; Louzguine, D. V.; Takeuchi, A.

    This document is part of Part 1 http://dx.doi.org/10.1007/97.etType="URL"/> 'Systems from Ag-Al-Ca to Au-Pd-Si' of Subvolume B 'Physical Properties of Ternary Amorphous Alloys' of Volume 37 'Phase Diagrams and Physical Properties of Nonequilibrium Alloys' of Landolt-Börnstein - Group III 'Condensed Matter'. It contains the Chapter 'Al-La-Nb (068)' with the content:

  18. Al-Cu-Zr (050)

    NASA Astrophysics Data System (ADS)

    Carow-Watamura, U.; Louzguine, D. V.; Takeuchi, A.

    This document is part of Part 1 http://dx.doi.org/10.1007/9getType="URL"/> 'Systems from Ag-Al-Ca to Au-Pd-Si' of Subvolume B 'Physical Properties of Ternary Amorphous Alloys' of Volume 37 'Phase Diagrams and Physical Properties of Nonequilibrium Alloys' of Landolt-Börnstein - Group III 'Condensed Matter'. It contains the Chapter 'Al-Cu-Zr (050)' with the content:

  19. Al-La-Ni (069)

    NASA Astrophysics Data System (ADS)

    Carow-Watamura, U.; Louzguine, D. V.; Takeuchi, A.

    This document is part of Part 1 http://dx.doi.org/10.1007/9getType="URL"/> 'Systems from Ag-Al-Ca to Au-Pd-Si' of Subvolume B 'Physical Properties of Ternary Amorphous Alloys' of Volume 37 'Phase Diagrams and Physical Properties of Nonequilibrium Alloys' of Landolt-Börnstein - Group III 'Condensed Matter'. It contains the Chapter 'Al-La-Ni (069)' with the content:

  20. Al-Au-La (010)

    NASA Astrophysics Data System (ADS)

    Carow-Watamura, U.; Louzguine, D. V.; Takeuchi, A.

    This document is part of Part 1 http://dx.doi.org/10.1007/9getType="URL"/> 'Systems from Ag-Al-Ca to Au-Pd-Si' of Subvolume B 'Physical Properties of Ternary Amorphous Alloys' of Volume 37 'Phase Diagrams and Physical Properties of Nonequilibrium Alloys' of Landolt-Börnstein - Group III 'Condensed Matter'. It contains the Chapter 'Al-Au-La (010)' with the content:

  1. Al-Ce-V (029)

    NASA Astrophysics Data System (ADS)

    Carow-Watamura, U.; Louzguine, D. V.; Takeuchi, A.

    This document is part of Part 1 http://dx.doi.org/10.1007/97.etType="URL"/> 'Systems from Ag-Al-Ca to Au-Pd-Si' of Subvolume B 'Physical Properties of Ternary Amorphous Alloys' of Volume 37 'Phase Diagrams and Physical Properties of Nonequilibrium Alloys' of Landolt-Börnstein - Group III 'Condensed Matter'. It contains the Chapter 'Al-Ce-V (029)' with the content:

  2. [How to handle unexpected biological abnormalities observed in the pre-donation workup for hematopoietic stem cell transplantation: an SFGM-TC report on pre-transplant cytomegalovirus, Epstein-Barr virus, Toxoplasma gondii, or syphilis IgM positive serology test].

    PubMed

    Duléry, R; Giraud, C; Beaumont, J-L; Bilger, K; Borel, C; Dhedin, N; Thiebaut, A; Willems, E; Alain, S; Alfandari, S; Dewilde, A; Jouet, J-P; Milpied, N; Yakoub-Agha, I

    2013-08-01

    In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of pre-transplant donor's cytomegalovirus, Epstein-Barr virus, Toxoplasma gondii, or syphilis IgM positive serology test.

  3. Comparing the Thermodynamic Behaviour of Al(1)+ZrO2(s) to Al(1)+Al2O3(s)

    NASA Technical Reports Server (NTRS)

    Copland, Evan

    2004-01-01

    In an effort to better determine the thermodynamic properties of Al(g) and Al2O(g). the vapor in equilibrium with Al(l)+ZrO2(s) was compared to the vapor in equilibrium with Al(l)+Al2O3(s) over temperature range 1197-to-1509K. The comparison was made directly by Knudsen effusion-cell mass spectrometry with an instrument configured for a multiple effusion-cell vapor source (multi-cell KEMS). Second law enthalpies of vaporization of Al(g) and Al2O(g) together with activity measurements show that Al(l)+ZrO2(s) is thermodynamically equivalent to Al(l)+Al2O3(s), indicating Al(l) remained pure and Al2O3(s) was present in the ZrO2-cell. Subsequent observation of the Al(l)/ZrO2 and vapor/ZrO2 interfaces revealed a thin Al2O3-layer had formed, separating the ZrO2-cell from Al(l) and Al(g)+Al2O(g), effectively transforming it into an Al2O3 effusion-cell. This behavior agrees with recent observations made for Beta-NiAl(Pt) alloys measured in ZrO2 effusion-cell.

  4. Crystal structure of a Staphylococcus aureus protein A domain complexed with the Fab fragment of a human IgM antibody: structural basis for recognition of B-cell receptors and superantigen activity.

    PubMed

    Graille, M; Stura, E A; Corper, A L; Sutton, B J; Taussig, M J; Charbonnier, J B; Silverman, G J

    2000-05-09

    Staphylococcus aureus produces a virulence factor, protein A (SpA), that contains five homologous Ig-binding domains. The interactions of SpA with the Fab region of membrane-anchored Igs can stimulate a large fraction of B cells, contributing to lymphocyte clonal selection. To understand the molecular basis for this activity, we have solved the crystal structure of the complex between domain D of SpA and the Fab fragment of a human IgM antibody to 2.7-A resolution. In the complex, helices II and III of domain D interact with the variable region of the Fab heavy chain (V(H)) through framework residues, without the involvement of the hypervariable regions implicated in antigen recognition. The contact residues are highly conserved in human V(H)3 antibodies but not in other families. The contact residues from domain D also are conserved among all SpA Ig-binding domains, suggesting that each could bind in a similar manner. Features of this interaction parallel those reported for staphylococcal enterotoxins that are superantigens for many T cells. The structural homology between Ig V(H) regions and the T-cell receptor V(beta) regions facilitates their comparison, and both types of interactions involve lymphocyte receptor surface remote from the antigen binding site. However, T-cell superantigens reportedly interact through hydrogen bonds with T-cell receptor V(beta) backbone atoms in a primary sequence-independent manner, whereas SpA relies on a sequence-restricted conformational binding with residue side chains, suggesting that this common bacterial pathogen has adopted distinct molecular recognition strategies for affecting large sets of B and T lymphocytes.

  5. Serodiagnosis of Tuberculosis: Comparison of Immunoglobulin A (IgA) Response to Sulfolipid I with IgG and IgM Responses to 2,3-Diacyltrehalose, 2,3,6-Triacyltrehalose, and Cord Factor Antigens

    PubMed Central

    Julián, Esther; Matas, Lurdes; Pérez, Andrés; Alcaide, José; Lanéelle, Marie-Antoinette; Luquin, Marina

    2002-01-01

    Nonpeptidic antigens from the Mycobacterium tuberculosis cell wall are the focus of extensive studies to determine their potential role as protective antigens or serological markers of tuberculous disease. Regarding this latter role and using an enzyme-linked immunosorbent assay, we have made a comparative study of the immunoglobulin G (IgG), IgM, and IgA antibody responses to four trehalose-containing glycolipids purified from M. tuberculosis: diacyltrehaloses, triacyltrehaloses, cord factor, and sulfolipid I (SL-I). Sera from 92 tuberculosis patients (taken before starting antituberculosis treatment) and a wide group of control individuals (84 sera from healthy donors, including purified protein derivative-negative, -positive, healed, and vaccinated individuals, and 52 sera from nontuberculous pneumonia patients), all from Spain, were studied. The results indicated a significantly elevated IgG and IgA antibody response in tuberculosis patients, compared with controls, with all the antigens used. SL-I was the best antigen studied, showing test sensitivities and specificities for IgG of 81 and 77.6%, respectively, and of 66 and 87.5% for IgA. Using this antigen and combining IgA and IgG antibody detection, high test specificity was achieved (93.7%) with a sensitivity of 67.5%. Currently, it is widely accepted that it is not possible to achieve sensitivities above 80% in tuberculosis serodiagnosis when using one antigen alone. Thus, we conclude that SL-I, in combination with other antigenic molecules, could be a useful antigen for tuberculosis serodiagnosis. PMID:12354881

  6. Evaluation of risk and diagnostic value of quantitative assays for anti-Toxoplasma gondii immunoglobulin A (IgA), IgE, and IgM and analytical study of specific IgG in immunodeficient patients.

    PubMed Central

    Pinon, J M; Foudrinier, F; Mougeot, G; Marx, C; Aubert, D; Toupance, O; Niel, G; Danis, M; Camerlynck, P; Remy, G

    1995-01-01

    To determine their prognostic and diagnostic values for toxoplasmosis in immunodepressed subjects, we assayed immunoglobulin A (IgA) and IgE antibodies by means of immunocapture (IC) tests, with revelation done by using a suspension of T. gondii (ICT). We also carried out a simultaneous analytical study of IgG antibodies on cellulose acetate membranes by using the comparative immunological profile method and an enzyme-linked immunofiltration assay (ELIFA). A total of 1,238 samples (serum, cerebrospinal fluid, and aqueous humor from 318 patients) were tested. IgA and IgE antibodies were detected in all heart, kidney, and liver transplant recipients with clinical manifestations of toxoplasmosis; IgA was detected in the aqueous humor of a patient with chorioretinitis. In patients with AIDS-related toxoplasmosis, including the cerebral form, IgA and IgE antibodies or a significant modification of ELIFA IgG values were observed in 38, 19, and 25% of patients, respectively. IgM was detected by ICT only in 12% of patients and aided the diagnosis in 1 of 71 patients. IC tests for specific IgA and IgE alone and combined with ELIFA were positive in 39 and 46% of patients who developed clinical toxoplasmosis, respectively. In a serial study of 16 patients in whom at least one of these three tests was positive, a significant immunological signal sometimes preceded clinical onset by 1, 6, and even 17 months. Similarly, in a group of human immunodeficiency virus-infected patients with evidence of previous exposure to T. gondii but no clinical manifestations, IgA, IgE, and IgA and/or IgE antibodies were detected in only 11, 4, and 12% of patients, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7790453

  7. Modeling of the ALS linac

    SciTech Connect

    Kim, C.H.

    1996-08-01

    The ALS injector linac is used for the Beam Test Facility (BTF) and the Damping Experiments when it is available in between the ALS filings. These experiments usually require higher quality beams and a better characterization than is normally required for ALS operations. This paper focuses on the beam emittance, energy tilt, and especially the longitudinal variation of the beam parameters. For instance, the authors want to avoid longitudinal variations at the low beta section of the BTF. On the other hand, a large energy tilt is required for post-acceleration compression of the bunch using an alpha magnet. The PARMELA code was modified to calculate and display longitudinal variations of the emittance ellipse. Using the Microsoft Development Studio under Windows NT environment the code can handle a much larger number of particles than was previously possible.

  8. Superconductivity in Al/Al2O3 interface

    NASA Astrophysics Data System (ADS)

    Palnichenko, A. V.; Vyaselev, O. M.; Mazilkin, A. A.; Khasanov, S. S.

    2016-06-01

    Metastable superconductivity at Tc ≈ 65 K has been observed in Al foil subjected to special oxidation process, according to the ac magnetic susceptibility and electrical resistance measurements. Comparison of the ac susceptibility and the dc magnetization measurements infers that the superconductivity arises within the interfacial granular layer formed during the oxidation process between metallic aluminum and its oxide.

  9. Baumard et al.'s moral markets lack market dynamics.

    PubMed

    Fessler, Daniel M T; Holbrook, Colin

    2013-02-01

    Market models are indeed indispensable to understanding the evolution of cooperation and its emotional substrates. Unfortunately, Baumard et al. eschew market thinking in stressing the supposed invariance of moral/cooperative behavior across circumstances. To the contrary, humans display contingent morality/cooperation, and these shifts are best accounted for by market models of partner choice for mutually beneficial collaboration.

  10. FTD and ALS: genetic ties that bind.

    PubMed

    Orr, Harry T

    2011-10-20

    Curiously, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), seemingly disparate neurodegenerative disorders, can be inherited together. Two groups (DeJesus-Hernandez et al. and Renton et al.) show that the long sought after ALS/FTD mutation on chromosomal region 9p is a hexanucleotide expansion in C90RF72. These studies, plus a study on X-linked ALS/FTD, provide molecular starting points for identifying pathways that link ALS and FTD pathogenesis.

  11. ALS - A unique design approach

    NASA Astrophysics Data System (ADS)

    Chamberlain, Roger A.

    1990-09-01

    An advanced launch system (ALS), which is intended to be flexible and to deliver a wide range of payloads at a reduced cost, is discussed. The ALS concept also features total quality management, modular subsystems, standardized interfaces, standardized missions, and off-line payload encapsulation. The technological improvements include manufacturing of dry structures, use of composite materials, adaptive guidance and control systems, and laser-initiated radar systems. The operational improvements range from paperless management, to rocket engine leak detection devices and automated ground operations.

  12. Dynamic Modeling of ALS Systems

    NASA Technical Reports Server (NTRS)

    Jones, Harry

    2002-01-01

    The purpose of dynamic modeling and simulation of Advanced Life Support (ALS) systems is to help design them. Static steady state systems analysis provides basic information and is necessary to guide dynamic modeling, but static analysis is not sufficient to design and compare systems. ALS systems must respond to external input variations and internal off-nominal behavior. Buffer sizing, resupply scheduling, failure response, and control system design are aspects of dynamic system design. We develop two dynamic mass flow models and use them in simulations to evaluate systems issues, optimize designs, and make system design trades. One model is of nitrogen leakage in the space station, the other is of a waste processor failure in a regenerative life support system. Most systems analyses are concerned with optimizing the cost/benefit of a system at its nominal steady-state operating point. ALS analysis must go beyond the static steady state to include dynamic system design. All life support systems exhibit behavior that varies over time. ALS systems must respond to equipment operating cycles, repair schedules, and occasional off-nominal behavior or malfunctions. Biological components, such as bioreactors, composters, and food plant growth chambers, usually have operating cycles or other complex time behavior. Buffer sizes, material stocks, and resupply rates determine dynamic system behavior and directly affect system mass and cost. Dynamic simulation is needed to avoid the extremes of costly over-design of buffers and material reserves or system failure due to insufficient buffers and lack of stored material.

  13. Large rectification magnetoresistance in nonmagnetic Al/Ge/Al heterojunctions

    NASA Astrophysics Data System (ADS)

    Zhang, Kun; Li, Huan-Huan; Grünberg, Peter; Li, Qiang; Ye, Sheng-Tao; Tian, Yu-Feng; Yan, Shi-Shen; Lin, Zhao-Jun; Kang, Shi-Shou; Chen, Yan-Xue; Liu, Guo-Lei; Mei, Liang-Mo

    2015-09-01

    Magnetoresistance and rectification are two fundamental physical properties of heterojunctions and respectively have wide applications in spintronics devices. Being different from the well known various magnetoresistance effects, here we report a brand new large magnetoresistance that can be regarded as rectification magnetoresistance: the application of a pure small sinusoidal alternating-current to the nonmagnetic Al/Ge Schottky heterojunctions can generate a significant direct-current voltage, and this rectification voltage strongly varies with the external magnetic field. We find that the rectification magnetoresistance in Al/Ge Schottky heterojunctions is as large as 250% at room temperature, which is greatly enhanced as compared with the conventional magnetoresistance of 70%. The findings of rectification magnetoresistance open the way to the new nonmagnetic Ge-based spintronics devices of large rectification magnetoresistance at ambient temperature under the alternating-current due to the simultaneous implementation of the rectification and magnetoresistance in the same devices.

  14. Large rectification magnetoresistance in nonmagnetic Al/Ge/Al heterojunctions

    PubMed Central

    Zhang, Kun; Li, Huan-huan; Grünberg, Peter; Li, Qiang; Ye, Sheng-tao; Tian, Yu-feng; Yan, Shi-shen; Lin, Zhao-jun; Kang, Shi-shou; Chen, Yan-xue; Liu, Guo-lei; Mei, Liang-mo

    2015-01-01

    Magnetoresistance and rectification are two fundamental physical properties of heterojunctions and respectively have wide applications in spintronics devices. Being different from the well known various magnetoresistance effects, here we report a brand new large magnetoresistance that can be regarded as rectification magnetoresistance: the application of a pure small sinusoidal alternating-current to the nonmagnetic Al/Ge Schottky heterojunctions can generate a significant direct-current voltage, and this rectification voltage strongly varies with the external magnetic field. We find that the rectification magnetoresistance in Al/Ge Schottky heterojunctions is as large as 250% at room temperature, which is greatly enhanced as compared with the conventional magnetoresistance of 70%. The findings of rectification magnetoresistance open the way to the new nonmagnetic Ge-based spintronics devices of large rectification magnetoresistance at ambient temperature under the alternating-current due to the simultaneous implementation of the rectification and magnetoresistance in the same devices. PMID:26387967

  15. AlSb/InAs/AlSb quantum wells

    NASA Technical Reports Server (NTRS)

    Kroemer, Herbert

    1990-01-01

    Researchers studied the InAs/AlSb system recently, obtaining 12nm wide quantum wells with room temperature mobilities up to 28,000 cm(exp 2)/V center dot S and low-temperature mobilities up to 325,000 cm(exp 2)/V center dot S, both at high electron sheet concentrations in the 10(exp 12)/cm(exp 2) range (corresponding to volume concentrations in the 10(exp 18)/cm(exp 2) range). These wells were not intentionally doped; the combination of high carrier concentrations and high mobilities suggest that the electrons are due to not-intentional modulation doping by an unknown donor in the AlSb barriers, presumably a stoichiometric defect, like an antisite donor. Inasmuch as not intentionally doped bulk AlSb is semi-insulating, the donor must be a deep one, being ionized only by draining into the even deeper InAs quantum well. The excellent transport properties are confirmed by other observations, like excellent quantum Hall effect data, and the successful use of the quantum wells as superconductive weak links between Nb electrodes, with unprecendentedly high critical current densities. The system is promising for future field effect transistors (FETs), but many processing problems must first be solved. Although the researchers have achieved FETs, the results so far have not been competitive with GaAs FETs.

  16. Effect of interface geometry on electron tunnelling in Al/Al2O3/Al junctions

    NASA Astrophysics Data System (ADS)

    Koberidze, M.; Feshchenko, A. V.; Puska, M. J.; Nieminen, R. M.; Pekola, J. P.

    2016-04-01

    We investigate how different interface geometries of an Al/Al2O3 junction, a common component of modern tunnel devices, affect electron transport through the tunnel barrier. We study six distinct Al/Al2O3 interfaces which differ in stacking sequences of the metal and the oxide surface atoms and the oxide termination. To construct model potential barrier profiles for each examined geometry, we rely on first-principles density-functional theory (DFT) calculations for the barrier heights and the shapes of the interface regions as well as on experimental data for the barrier widths. We show that even tiny variations in the atomic arrangement at the interface cause significant changes in the tunnel barrier parameters and, consequently, in electron transport properties. Especially, we find that variations in the crucial barrier heights and widths can be as large as 2 eV and 5 Å, respectively. Finally, to gain information about the average properties of the measured junction, we fit the conductance calculated within the Wentzel-Kramers-Brillouin approximation to the experimental data and interpret the fit parameters with the help of the DFT results.

  17. B cells that simultaneously express surface IgM and IgE in Nippostrongylus brasiliensis-infected SJA/9 mice do not provide evidence for isotype switching without gene deletion.

    PubMed Central

    Katona, I M; Urban, J F; Finkelman, F D

    1985-01-01

    Recently, it has been reported that in SJA/9 mice infected with Nippostrongylus brasiliensis there are increased numbers of lymphoid cells positive for surface IgM and IgE (sIgM+ and sIgE+) even though they fail to secrete IgE, that both the sIgM and sIgE on these cells are intrinsic, and that there has been no deletion of genes for the Ig heavy chain constant region in these cells. These observations support a nondeletional model for Ig isotype switching. We have now reexamined the nature of sIgE on sIgE+ spleen and mesenteric lymph node cells of N. brasiliensis-infected SJA/9 mice, and the following observations lead us to believe that this sIgE is cytophilic rather than intrinsic: (i) Only approximately 50% of the N. brasiliensis-infected SJA/9 mice have detectable percentages of sIgE+ lymphoid cells. All mice with detectable sIgE+ lymphocytes have lymphocytes positive for intracytoplasmic IgE (cIgE+) and secrete IgE in vitro, while cIgE+ cells and IgE secretion are absent from N. brasiliensis-infected SJA/9 mice that lack sIgE+ cells. (ii) SJA/9 B lymphocytes have receptors for IgE: expression of these receptors is increased in N. brasiliensis-infected mice that have sIgE+ lymphocytes, but not in infected SJA/9 mice that lack sIgE+ lymphocytes. (iii) Treatment of sIgM+ sIgD+ sIgE+ cells for 1 min with dilute acid removes most sIgE but does not affect expression of sIgM or sIgD. (iv) The removal of mouse IgE from sIgE+ B cells facilitates the binding of exogenous rat IgE. (v) The small amount of sIgE that is reexpressed during a period of in vitro culture after acid treatment is blocked by inclusion of exogenous rat IgE in the culture medium. These observations show that most sIgM+ sIgE+ B cells in N. brasiliensis-infected SJA/9 mice do not express intrinsic sIgE; thus studies using these cells to determine mechanisms of Ig isotype switching are inconclusive. PMID:3155861

  18. Establishment of an Algorithm Using prM/E- and NS1-Specific IgM Antibody-Capture Enzyme-Linked Immunosorbent Assays in Diagnosis of Japanese Encephalitis Virus and West Nile Virus Infections in Humans.

    PubMed

    Galula, Jedhan U; Chang, Gwong-Jen J; Chuang, Shih-Te; Chao, Day-Yu

    2016-02-01

    The front-line assay for the presumptive serodiagnosis of acute Japanese encephalitis virus (JEV) and West Nile virus (WNV) infections is the premembrane/envelope (prM/E)-specific IgM antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA). Due to antibody cross-reactivity, MAC-ELISA-positive samples may be confirmed with a time-consuming plaque reduction neutralization test (PRNT). In the present study, we applied a previously developed anti-nonstructural protein 1 (NS1)-specific MAC-ELISA (NS1-MAC-ELISA) on archived acute-phase serum specimens from patients with confirmed JEV and WNV infections and compared the results with prM/E containing virus-like particle-specific MAC-ELISA (VLP-MAC-ELISA). Paired-receiver operating characteristic (ROC) curve analyses revealed no statistical differences in the overall assay performances of the VLP- and NS1-MAC-ELISAs. The two methods had high sensitivities of 100% but slightly lower specificities that ranged between 80% and 100%. When the NS1-MAC-ELISA was used to confirm positive results in the VLP-MAC-ELISA, the specificity of serodiagnosis, especially for JEV infection, was increased to 90% when applied in areas where JEV cocirculates with WNV, or to 100% when applied in areas that were endemic for JEV. The results also showed that using multiple antigens could resolve the cross-reactivity in the assays. Significantly higher positive-to-negative (P/N) values were consistently obtained with the homologous antigens than those with the heterologous antigens. JEV or WNV was reliably identified as the currently infecting flavivirus by a higher ratio of JEV-to-WNV P/N values or vice versa. In summary of the above-described results, the diagnostic algorithm combining the use of multiantigen VLP- and NS1-MAC-ELISAs was developed and can be practically applied to obtain a more specific and reliable result for the serodiagnosis of JEV and WNV infections without the need for PRNT. The developed algorithm should provide great

  19. Relativity and Al^+ Optical Clocks

    NASA Astrophysics Data System (ADS)

    Chou, Chin-Wen; Hume, David B.; Wineland, David J.; Rosenband, Till

    2010-03-01

    We have constructed an optical clock based on quantum logic spectroscopy of an Al+ ion that has a fractional frequency inaccuracy of 8.6x10-18. The frequency of the ^1S0<->^3P0 clock transition is compared to that of a previously constructed Al^+ optical clock with a statistical measurement uncertainty of 7.0x10-18. The two clocks exhibit a relative stability of 2.8x10-15&-1/2circ;, and a fractional frequency difference of -1.8x10-17, consistent with the accuracy limit of the older clock. By comparing the frequencies of the clocks, we have observed relativistic effects, such as time dilation due to velocities less than 10 m/s and the gravitational red shift from a 0.33 m height change of one of the clocks.

  20. [Coagulation behavior of Al13 species].

    PubMed

    Hu, Cheng-zhi; Liu, Hui-juan; Qu, Jiu-hui

    2006-12-01

    Coagulation behavior of Al13 species was examined in synthetic water with high alkalinity and high humic acid concentration from viewpoint of the transformation of Al hydrolysis products during the coagulation process. The results indicated that coagulation efficiency of Al coagulants positively correlated with the content of Al13 in the coagulation process. Aluminum chloride (AlCl3) was more effective than polyaluminum chloride (PACI) in removing turbidity and dissolved organic matter in the synthetic water because AlCl3 could not only generate Al13 species but also function as pH control agent in the coagulation process. During coagulation process pH control can improve coagulation process through regulating Al speciation, and AlCl3 benefited most from pH control.

  1. Synthesis of AlN/Al Polycrystals along with Al Nanoparticles Using Thermal Plasma Route

    SciTech Connect

    Kanhe, Nilesh S.; Nawale, A. B.; Kulkarni, N. V.; Bhoraskar, S. V.; Mathe, V. L.; Das, A. K.

    2011-07-15

    This paper for the first time reports the (200) oriented growth of hexagonal Aluminum nitride crystals during synthesis of aluminum nanoparticles in dc transferred arc thermal plasma reactor by gas phase condensation in nitrogen plasma. The structural and morphological study of as synthesized AlN crystal and aluminium nanoparticles was done by using the x-ray diffraction method, scanning electron microscopy and transmission electron microscopy.

  2. Investigations of Al-Dalang and Al-Hawashat meteorites

    NASA Astrophysics Data System (ADS)

    Gismelseed, A. M.; Abdallah, S. B.; Al-Rawas, A. D.; Al-Mabsali, F. N.; Widatallah, H. M.; Elzain, M. E.; Yousif, A. A.; Ericsson, T.; Annersten, H.

    2016-12-01

    Mössbauer spectroscopy, X-ray diffraction (XRD) measurements, and electron microprobe analysis (EMPA) have been performed on two meteorites named Al-Dalang and Al-Hawashat after identifying their falling sites in the Western region of Sudan. These two meteorites are ordinary chondrites with similar mineralogy. XRD and EMPA show that the two specimens consist of primary olivine, ortho-pyroxene and later crystallising clino-pyroxene as reaction rims against plagioclase. Fe-metal phases are dominated by kamacite (≈6 wt.% Ni) and minor amounts of tetrataenite (≈52 wt.% Ni). Troilite (FeS) and alabandite (MnS) are optically observed as sulphide phases. The Mössbauer measurements at 295 and 78 K are in agreement with the above characterizations, showing at least two paramagnetic doublets which are assigned to olivine and pyroxene and magnetic sextets assigned to kamacite (hyperfine field ≈33.5 T) and troilite FeS (hyperfine field ≈31 T).

  3. Al-Al2O3-Pd junction hydrogen sensor

    NASA Astrophysics Data System (ADS)

    Okuyama, K.; Takinami, N.; Chiba, Y.; Ohshima, S.; Kambe, S.

    1994-07-01

    Al-Al2O3-Pd MIM (metal insulator metal) junctions fabricated on a glass substrate were tested as hydrogen sensors. The I-V (current versus voltage) characteristics of the junctions were measured at room temperature in a vacuum of 10-5 Torr and in H2 gas of 10-2-100 Torr. A significant increase in the current was observed upon introduction of H2 gas. This phenomenon is believed to occur due to the work function lowering of the hydrogen-absorbed Pd top electrode. The rise time was on the order of minutes, while the recovery time when hydrogen was purged was more than 20 h. However, when the junction was placed in an oxidizing ambient such as air, the recovery time was drastically reduced to the order of minutes, indicating that the device is operative as a hydrogen sensor in the atmospheric ambient. Hydrogen adsorption and desorption behavior of the Pd film was also investigated using a Pd coated quartz microbalance, and the results explained the current response of the Pd MIM junction to hydrogen in the presence of oxygen.

  4. Reverse enzyme-linked immunosorbent assay using monoclonal antibodies against SAG1-related sequence, SAG2A, and p97 antigens from Toxoplasma gondii to detect specific immunoglobulin G (IgG), IgM, and IgA antibodies in human sera.

    PubMed

    Carvalho, Fernando R; Silva, Deise A O; Cunha-Júnior, Jair P; Souza, Maria A; Oliveira, Taísa C; Béla, Samantha R; Faria, Gabriele G; Lopes, Carolina S; Mineo, José R

    2008-08-01

    The present study aimed to evaluate the performance of three monoclonal antibodies (MAbs) in reverse enzyme-linked immunosorbent assays (ELISAs) for detecting immunoglobulin G (IgG), IgM, and IgA antibodies against Toxoplasma gondii in 175 serum samples from patients at different stages of T. gondii infection, as defined by both serological and clinical criteria, as follows: recent (n = 45), transient (n = 40), and chronic (n = 55) infection as well as seronegative subjects (n = 35). The results were compared with those obtained by indirect ELISA using soluble Toxoplasma total antigen (STAg). Our data demonstrated that MAb A3A4 recognizes a conformational epitope in SAG1-related-sequence (SRS) antigens, while A4D12 and 1B8 recognize linear epitopes defined as SAG2A surface antigen and p97 cytoplasmatic antigen, respectively. Reverse ELISA for IgG with A3A4 or A4D12 MAbs was highly correlated with indirect ELISA for anti-STAg IgG, whereas only A4D12 reverse ELISA showed high correlation with indirect ELISA for IgM and IgA isotypes. To our knowledge, this is the first report analyzing the performance of a reverse ELISA for simultaneous detection of IgG, IgM, and IgA isotypes active toward native SAG2A, SRS, and p97 molecules from STAg, using a panel of human sera from patients with recent and chronic toxoplasmosis. Thus, reverse ELISA based on the capture of native SAG2A and SRS antigens of STAg by MAbs could be an additional approach for strengthening the helpfulness of serological tests assessing the stage of infection, particularly in combination with highly sensitive and specific assays that are frequently used nowadays for diagnosis of toxoplasmosis during pregnancy or congenital infection in newborns.

  5. Ab initio modeling of zincblende AlN layer in Al-AlN-TiN multilayers

    DOE PAGES

    Yadav, S. K.; Wang, J.; Liu, X. -Y.

    2016-06-13

    An unusual growth mechanism of metastable zincblende AlN thin film by diffusion of nitrogen atoms into Al lattice is established. Using first-principles density functional theory, we studied the possibility of thermodynamic stability of AlN as a zincblende phase due to epitaxial strains and interface effect, which fails to explain the formation of zincblende AlN. We then compared the formation energetics of rocksalt and zincblende AlN in fcc Al through direct diffusion of nitrogen atoms to Al octahedral and tetrahedral interstitials. Furthermore, the formation of a zincblende AlN thin film is determined to be a kinetically driven process, not a thermodynamicallymore » driven process.« less

  6. NiAl-base composite containing high volume fraction of AlN for advanced engines

    NASA Technical Reports Server (NTRS)

    Hebsur, Mohan (Inventor); Whittenbeger, John D. (Inventor); Lowell, Carl F. (Inventor)

    1994-01-01

    A particulate reinforced NiAl-AlN composite alloy has a NiAl matrix and greater than about 13 volume percent fine particles of AlN within the matrix. The particles preferably have a diameter from about 15 nanometers to about 50 nanometers. The particulate reinforced NiAl-AlN composite alloy may be prepared by cryomilling prealloyed NiAl in liquid nitrogen using grinding media having a diameter of from about 2 to 6 mm at an impeller speed of from about 450 RPM to about 800 RPM. The cryomilling may be done for a duration of from about 4 hours to about 20 hours to obtain a cryomilled powder. The cryomilled powder may be consolidated to form the particulate reinforced NiAl-AlN composite alloy. The particulate reinforced alloy can further include a toughening alloy. The toughening alloy may include NiCrAlY, FeCrAlY, and FeAl.

  7. Benefits for Military Veterans with ALS

    MedlinePlus

    ... Advocate Get Involved Donate Military Veterans Resources for Military Veterans, Families & Survivors The ALS Association is working everyday to ... and Caregivers Newly Diagnosed Clinical Trials Familial ALS Military Veterans For Caregivers Resources Read stories ... Site ...

  8. Cenomanian-Turonian biostratigraphy of the Jardas Al Abid area, Al Jabal Al Akhdar, northeast Libya

    NASA Astrophysics Data System (ADS)

    El Qot, Gamal M.; Abdulsamad, Esam O.

    2016-09-01

    The Upper Cenomanian-Turonian succession exposed at Jardas al'Abid area consists mainly of carbonates with siliciclastic intercalations. This succession is subdivided lithostratigraphically into: Qasr al'Abid (Late Cenomanian) and Al Baniyah (Late Cenomanian-Coniacian) formations. This sequence is relatively rich in macrofossil assemblages especially bivalves, gastropods, and echinoids with rare ammonites. Based on the first occurrence (FO) and last occurrence (LO) of some index species of these macrofossil groups, an integrated biostratigraphic framework has been constructed. The studied Cenomanian-Turonian sequence is subdivided biostratigraphically into three ammonite biozones; Pseudaspidoceras pseudonodosoides Total Range Zone, Choffaticeras segne Total Range Zone, and Coilopoceras requienianum Total Range Zone. Based on the rest of macrofossil assemblages other than the ammonites, eight biozones were recognized; Mecaster batnensis Total Range Zone, Ceratostreon flabellatum-Neithea dutrugei Acme Zone, Costagyra olisiponensis Acme Zone, Pycnodonte (Phygraea) vesicularis vesiculosa Acme Zone, Mytiloides labiatus Total Range Zone = Mecaster turonensis Acme Zone, Rachiosoma rectilineatum-Curvostrea rouvillei-Tylostoma (T.) globosum Assemblage Zone, Radiolites sp.-Apricardia? matheroni Total Range Zone, and Nerinea requieniana Total Range Zone. Most of the proposed biozones are recorded for the first time from Libya. The integration among these biozones as well as local and inter-regional correlation of the biozones have been discussed. The stage boundaries of the studied stratigraphic intervals are discussed, where the Cenomanian/Turonian boundary is delineated at the last occurrence (LO) of Pseudaspidoceras pseudonodosoides (Choffat), while the Turonian/Coniacian boundary is delineated arbitrary being agree with the LO of the Turonian fauna.

  9. Effects of the Al content on pore structures of porous TieAl alloys

    SciTech Connect

    Jaing, Y; He, Y H; Xu, N P; Zou, J; Huang, B; Lui, C T

    2008-01-01

    Porous TieAl alloys with different nominal compositions were fabricated through a reactive synthesis of Ti and Al elemental powders. It has been found that the pore parameters vary with the Al contents, indicating that the nature of the pores can be manipulated through changing the Al contents. In addition, detailed structural characterizations showed that the fabricated porous TieAl alloys can have three crystalline phases (i.e., a2-Ti3Al, g-TiAl, and TiAl3) when using different compositions. The fundamental reasons behind these phenomena have been explored.

  10. Photoelectrical, photophysical and photocatalytic properties of Al based MOFs: MIL-53(Al) and MIL-53-NH2(Al)

    NASA Astrophysics Data System (ADS)

    An, Yang; Li, Huiliang; Liu, Yuanyuan; Huang, Baibiao; Sun, Qilong; Dai, Ying; Qin, Xiaoyan; Zhang, Xiaoyang

    2016-01-01

    Two Al based MOFs (MIL-53(Al) and MIL-53-NH2 (Al)) were synthesized, and their photoelectrical, photophysical and photocatalytic properties towards oxygen evolution from water were investigated. Different from the ligand to metal charge transfer process previously reported, we proposes a new photocatalytic mechanism based on electron tunneling according to the results of theoretical calculation, steady state and time resolved fluorescence spectra. The organic linkers absorb photons, giving rise to electrons and holes. Then, the photogenerated electrons tunnel through the AlO6-octahedra, which not only inhibit the recombination of photogenerated charge carriers, but also is a key factor to the photocatalytic activity of Al based MOFs.

  11. Framework Al zoning in zeolite ECR-1.

    PubMed

    Shin, Jiho; Ahn, Nak Ho; Cho, Sung June; Ren, Limin; Xiao, Feng-Shou; Hong, Suk Bong

    2014-02-25

    Rietveld analyses of the synchrotron X-ray diffraction data for various cation forms of zeolite ECR-1 have demonstrated framework Al zoning, which parallels the alternation of Al-rich maz and Al-poor mor layers. This can be further supported by notable differences in the average bond valence of its 10 crystallographically distinct tetrahedral sites.

  12. Opportunity's 'Rub al Khali' Panorama

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site] Click on the image for Opportunity's 'Rub al Khali' Panorama (QTVR)

    This panoramic image, dubbed 'Rub al Khali,' was acquired by NASA's Mars Exploration Rover Opportunity on the plains of Meridiani during the period from the rover's 456th to 464th sols on Mars (May 6 to May 14, 2005). Opportunity was about 2 kilometers (1.2 miles) south of 'Endurance Crater' at a place known informally as 'Purgatory Dune.'

    The rover was stuck in the dune's deep fine sand for more than a month. 'Rub al Khali' (Arabic translation: 'the empty quarter') was chosen as the name for this panorama because it is the name of a similarly barren, desolate part of the Saudi Arabian desert on Earth.

    The view spans 360 degrees. It consists of images obtained in 97 individual pointings of the panoramic camera. The camera took images with five camera filters at each pointing. This 22,780-by-6,000-pixel mosaic is an approximately true-color rendering generated using the images acquired through filters admitting light wavelengths of 750, 530, and 480 nanometers.

    Lighting varied during the nine sols it took to acquire this panorama, resulting in some small image seams within the mosaic. These seams have been smoothed in sky parts of the mosaic to better simulate the vista that a person would see if able to view it all at the same time on Mars.

    Opportunity's tracks leading back to the north (center of the panorama) are a reminder of the rover's long trek from Endurance Crater. The deep ruts dug by Opportunity's wheels as it became stuck in the sand appear in the foreground. The crest and trough of the last ripple the rover crossed before getting stuck is visible in the center. These wind-formed sand features are only about 10 to 15 centimeters (4 to 6 inches) tall. The crest of the actual ripple where the rover got stuck can be seen just to the right of center. The tracks and a few other places on and near ripple crests can

  13. Instandhaltungsmanagement als Gestaltungsfeld Ganzheitlicher Produktionssysteme

    NASA Astrophysics Data System (ADS)

    Dombrowski, Uwe; Schulze, Sven; Otano, Isabel Crespo

    Sich kontinuierlich verändernde Rahmenbedingungen, wie beispielsweise eine steigende Variantenvielfalt, verkürzte Produktlebenszyklen sowie Kundenforderungen nach höherer Qualität, kürzeren Lieferzeiten und geringeren Kosten, fordern von produzierenden Unternehmen eine stetige Anpassung der Prozesse, der Organisation und der Strukturen. Seit den 90er Jahren versuchen immer mehr deutsche Unternehmen diesen veränderten Anforderungen mit der Einführung eines Ganzheitlichen Produktionssystems (GPS) zu begegnen. Ganzheitliche Produktionssysteme sind dabei in ihren Grundlagen an das Toyota Produktionssystem angelehnt, vereinigen aber auch weitere Methoden zu einem unternehmensspezifischen Regelwerk. Im Rahmen des langfristigen Trends zu unternehmensindividuellen Produktionssystemen wird sowohl in der Industrie als auch in der Forschung intensiv über das Toyota Produktionssystem, Lean Production, Lean Management und Ganzheitliche Produktionssysteme diskutiert, werden Konzepte zu Implementierung und Betrieb erstellt und die Wirtschaftlichkeit untersucht.

  14. Systems Engineering Techniques for ALS Decision Making

    NASA Technical Reports Server (NTRS)

    Rodriquez, Luis F.; Drysdale, Alan E.; Jones, Harry; Levri, Julie A.

    2004-01-01

    The Advanced Life Support (ALS) Metric is the predominant tool for predicting the cost of ALS systems. Metric goals for the ALS Program are daunting, requiring a threefold increase in the ALS Metric by 2010. Confounding the problem, the rate new ALS technologies reach the maturity required for consideration in the ALS Metric and the rate at which new configurations are developed is slow, limiting the search space and potentially giving the perspective of a ALS technology, the ALS Metric may remain elusive. This paper is a sequel to a paper published in the proceedings of the 2003 ICES conference entitled, "Managing to the metric: an approach to optimizing life support costs." The conclusions of that paper state that the largest contributors to the ALS Metric should be targeted by ALS researchers and management for maximum metric reductions. Certainly, these areas potentially offer large potential benefits to future ALS missions; however, the ALS Metric is not the only decision-making tool available to the community. To facilitate decision-making within the ALS community a combination of metrics should be utilized, such as the Equivalent System Mass (ESM)-based ALS metric, but also those available through techniques such as life cycle costing and faithful consideration of the sensitivity of the assumed models and data. Often a lack of data is cited as the reason why these techniques are not considered for utilization. An existing database development effort within the ALS community, known as OPIS, may provide the opportunity to collect the necessary information to enable the proposed systems analyses. A review of these additional analysis techniques is provided, focusing on the data necessary to enable these. The discussion is concluded by proposing how the data may be utilized by analysts in the future.

  15. Wear behavior of Al-Al{sub 3}Ti composite manufactured by a centrifugal method

    SciTech Connect

    Watanabe, Yoshimi; Yamanaka, Noboru; Fukui, Yasuyoshi

    1999-12-01

    The purpose of the present study was to develop a wear-resistant, light Al-Al{sub 3}Ti composite material. An Al-Al{sub 3}Ti composite specimen was machined from a thick-walled tube of Al-Al{sub 3}Ti functionally graded material (FGM) manufactured by the centrifugal method from a commercial ingot of Al-5 mass% Ti master alloy. The alloy was heated to a temperature where solid Al{sub 3}Ti particles resided in a liquid Al matrix, and then the centrifugal method was carried out. Al{sub 3}Ti particles in a commercial alloy ingot exist as platelets, and this shape was maintained through the casting. Three kinds of wear specimens were prepared, taking into account the morphology of the Al{sub 3}Ti particles in the thick-walled FGM tube; the Al{sub 3}Ti particles were arranged with their platelet planes nearly normal to the radial direction as a result of the applied centrifugal force. The wear resistance of the Al-Al{sub 3}Ti composite was significantly higher than that of pure Al. Wear-resistance anisotropy and dissolution of the Al{sub 3}Ti into the Al matrix at the near-surface region, around 100 {micro}m in depth, were also observed. The mechanism of the supersaturated-layer formation and the origin of the anisotropic wear resistance are discussed.

  16. Magnetism of Al-substituted magnetite reduced from Al-hematite

    NASA Astrophysics Data System (ADS)

    Jiang, Zhaoxia; Liu, Qingsong; Zhao, Xiang; Roberts, Andrew P.; Heslop, David; Barrón, Vidal; Torrent, José

    2016-06-01

    Aluminum-substituted magnetite (Al-magnetite) reduced from Al-substituted hematite or goethite (Al-hematite or Al-goethite) is an environmentally important constituent of magnetically enhanced soils. In order to characterize the magnetic properties of Al-magnetite, two series of Al-magnetite samples were synthesized through reduction of Al-hematite by a mixed gas (80% CO2 and 20% CO) at 395°C for 72 h in a quartz tube furnace. Al-magnetite samples inherited the morphology of their parent Al-hematite samples, but only those transformed from Al-hematite synthesized at low temperature possessed surficial micropores, which originated from the release of structural water during heating. Surface micropores could thus serve as a practical fingerprint of fire or other high-temperature mineralogical alteration processes in natural environments, e.g., shear friction in seismic zones. In addition, Al substitution greatly affects the magnetic properties of Al-magnetite. For example, coercivity (Bc) increases with increasing Al content and then decreases slightly, while the saturation magnetization (Ms), Curie temperature (Tc), and Verwey transition temperature (Tv) all decrease with increasing Al content due to crystal defect formation and dilution of magnetic ions caused by Al incorporation. Moreover, different trends in the correlation between Tc and Bc can be used to discriminate titanomagnetite from Al-magnetite, which is likely to be important in environmental and paleomagnetic studies, particularly in soil.

  17. Reply to Vance et al.

    SciTech Connect

    Woon-Chee Yee; Elliott, J.L; Kwon, J.M.; Goodfellow, P.

    1996-07-01

    In our report of a family with a motor and sensory polyneuropathy that was linked to chromosome 3q, we classified this neuropathy as a form of hereditary motor and sensory neuropathy II (HMSN II, also known as {open_quotes}CMT2{close_quotes}). Doubts have been raised by Vance et al. as to whether this neuropathy should be classified as hereditary sensory autonomic neuropathy I (HSAN I) instead of HMSN II. While it is reasonable to raise such doubts, we believe that the neuropathy is best designated as HMSN II for the reasons described below. The group of disorders described as HSAN are characterized by primary or predominant involvement of sensory and autonomic neurons that fail to develop or that undergo atrophy and degeneration. These disorders were extensively reviewed by Dyck and Ohta, who initially described them as the hereditary sensory neuropathies (HSN). It was Dyck who subsequently suggested that these disorders be designated HSAN rather than HSN, because of the presence of autonomic involvement. 8 refs.

  18. Growth and Stress-induced Transformation of Zinc blende AlN Layers in Al-AlN-TiN Multilayers

    PubMed Central

    Li, Nan; Yadav, Satyesh K.; Wang, Jian; Liu, Xiang-Yang; Misra, Amit

    2015-01-01

    AlN nanolayers in sputter deposited {111}Al/AlN/TiN multilayers exhibit the metastable zinc-blende-structure (z-AlN). Based on density function theory calculations, the growth of the z-AlN is ascribed to the kinetically and energetically favored nitridation of the deposited aluminium layer. In situ nanoindentation of the as-deposited {111}Al/AlN/TiN multilayers in a high-resolution transmission electron microscope revealed the z-AlN to wurzite AlN phase transformation through collective glide of Shockley partial dislocations on every two {111} planes of the z-AlN. PMID:26681109

  19. Growth and stress-induced transformation of zinc blende AlN layers in Al-AlN-TiN multilayers

    DOE PAGES

    Li, Nan; Yadav, Satyesh K.; Wang, Jian; ...

    2015-12-18

    We report that AlN nanolayers in sputter deposited {111}Al/AlN/TiN multilayers exhibit the metastable zinc-blende-structure (z-AlN). Based on density function theory calculations, the growth of the z-AlN is ascribed to the kinetically and energetically favored nitridation of the deposited aluminium layer. In situ nanoindentation of the as-deposited {111}Al/AlN/TiN multilayers in a high-resolution transmission electron microscope revealed the z-AlN to wurzite AlN phase transformation through collective glide of Shockley partial dislocations on every two {111} planes of the z-AlN.

  20. Orientation relationship of eutectoid FeAl and FeAl2

    PubMed Central

    Scherf, A.; Kauffmann, A.; Kauffmann-Weiss, S.; Scherer, T.; Li, X.; Stein, F.; Heilmaier, M.

    2016-01-01

    Fe–Al alloys in the aluminium range of 55–65 at.% exhibit a lamellar microstructure of B2-ordered FeAl and triclinic FeAl2, which is caused by a eutectoid decomposition of the high-temperature Fe5Al8 phase, the so-called ∊ phase. The orientation relationship of FeAl and FeAl2 has previously been studied by Bastin et al. [J. Cryst. Growth (1978 ▸), 43, 745] and Hirata et al. [Philos. Mag. Lett. (2008 ▸), 88, 491]. Since both results are based on different crystallographic data regarding FeAl2, the data are re-evaluated with respect to a recent re-determination of the FeAl2 phase provided by Chumak et al. [Acta Cryst. (2010 ▸), C66, i87]. It is found that both orientation relationships match subsequent to a rotation operation of 180° about a 〈112〉 crystallographic axis of FeAl or by applying the inversion symmetry of the FeAl2 crystal structure as suggested by the Chumak data set. Experimental evidence for the validity of the previously determined orientation relationships was found in as-cast fully lamellar material (random texture) as well as directionally solidified material (∼〈110〉FeAl || solidification direction) by means of orientation imaging microscopy and global texture measurements. In addition, a preferential interface between FeAl and FeAl2 was identified by means of trace analyses using cross sectioning with a focused ion beam. On the basis of these habit planes the orientation relationship between the two phases can be described by (01)FeAl || (114) and [111]FeAl || [10]. There is no evidence for twinning within FeAl lamellae or alternating orientations of FeAl lamellae. Based on the determined orientation and interface data, an atomistic model of the structure relationship of Fe5Al8, FeAl and FeAl2 in the vicinity of the eutectoid decomposition is derived. This model is analysed with respect to the strain which has to be accommodated at the interface of FeAl and FeAl2. PMID:27047304

  1. Reactivity of aluminum cluster anions with ammonia: selective etching of Al11(-) and Al12(-).

    PubMed

    Grubisic, Andrej; Li, Xiang; Gantefoer, Gerd; Bowen, Kit H; Schnöckel, Hansgeorg; Tenorio, Francisco J; Martinez, Ana

    2009-11-14

    Reactivity of aluminum cluster anions toward ammonia was studied via mass spectrometry. Highly selective etching of Al(11)(-) and Al(12)(-) was observed at low concentrations of ammonia. However, at sufficiently high concentrations of ammonia, all other sizes of aluminum cluster anions, except for Al(13)(-), were also observed to deplete. The disappearance of Al(11)(-) and Al(12)(-) was accompanied by concurrent production of Al(11)NH(3)(-) and Al(12)NH(3)(-) species, respectively. Theoretical simulations of the photoelectron spectrum of Al(11)NH(3)(-) showed conclusively that its ammonia moiety is chemisorbed without dissociation, although in the case of Al(12)NH(3)(-), dissociation of the ammonia moiety could not be excluded. Moreover, since differences in calculated Al(n)(-) + NH(3) (n=9-12) reaction energies were not able to explain the observed selective etching of Al(11)(-) and Al(12)(-), we concluded that thermodynamics plays only a minor role in determining the observed reactivity pattern, and that kinetics is the more influential factor. In particular, the conversion from the physisorbed Al(n)(-)(NH(3)) to chemisorbed Al(n)NH(3)(-) species is proposed as the likely rate-limiting step.

  2. First-principles study of the Al(001)-Al3Nb(001) interfacial properties

    NASA Astrophysics Data System (ADS)

    Ding, Yanhong; Xu, Rui

    2017-03-01

    The adhesion, interfacial energy and bonding on fcc-Al(001)/D022-Al3Nb(001) interface were investigated using density functional calculations. Considering different terminations of Al3Nb(001) (Al+Nb-terminated and Al-terminated) and stacking sites (top-, bridge- and center-sites), six Al(001)/Al3Nb(001) models were calculated. For the models with same stacking site, Al+Nb-terminated model has larger work of adhesion (Wad) than the Al-terminated one. For the models with same termination, the work of adhesion increases, and the interface energy decreases as the order of center-sited, bridge-sited and top-sited. Al+Nb-terminated-center-sited and Al-terminated-center-sited models are more stable among six models. The interfacial bonding was discussed with analysis of valence electron density distribution and partial density of states (PDOS). The bonding is mainly contributed from Al-Nb covalent bonds and Al-Al metallic interactions.

  3. Interfacial Phenomena in Al/Al, Al/Cu, and Cu/Cu Joints Soldered Using an Al-Zn Alloy with Ag or Cu Additions

    NASA Astrophysics Data System (ADS)

    Pstruś, Janusz; Gancarz, Tomasz

    2014-05-01

    The studies of soldered joints were carried out in systems: Al/solder/Al, Al/solder/Cu, Cu/solder/Cu, where the solder was (Al-Zn)EUT, (Al-Zn)EUT with 0.5, 1.0, and 1.5 at.% of Ag and (Al-Zn)EUT with 0.5, 1.0, and 1.5 at.% of Cu addition. Brazing was performed at 500 °C for 3 min. The EDS analysis indicated that the composition of the layers starting from the Cu pad was CuZn, Cu5Zn8, and CuZn4, respectively. Wetting tests were performed at 500 °C for 3, 8, 15, and 30 min, respectively. Thickness of the layers and their kinetics of growth were measured based on the SEM micrographs. The formation of interlayers was not observed from the side of Al pads. On the contrary, dissolution of the Al substrate and migration of Al-rich particles into the bulk of the solder were observed.

  4. Genetics of Familial and Sporadic ALS

    ClinicalTrials.gov

    2017-01-04

    Amyotrophic Lateral Sclerosis (ALS); Familial Amyotrophic Lateral Sclerosis; Amyotrophic Lateral Sclerosis With Frontotemporal Dementia; Lou Gehrig's Disease; Motor Neuron Disease; Primary Lateral Sclerosis

  5. Spin-dependent tunneling junctions with AlN and AlON barriers

    NASA Astrophysics Data System (ADS)

    Sharma, Manish; Nickel, Janice H.; Anthony, Thomas C.; Wang, Shan X.

    2000-10-01

    We report on ferromagnetic spin-dependent tunneling (SDT) junctions with NiFe/AlN/NiFe and NiFe/AlON/NiFe structures. Good barriers were formed by plasma nitridation and oxy-nitridation of Al films. Tunneling magnetoresistance ratios (TMR) up to 18% were observed at room temperature. The devices exhibit lower resistance-area products than those seen in reference junctions with Al2O3 barriers. The degradation in TMR at higher bias voltages is found to be less than that found in standard alumina junctions. AlN and AlON could thus be alternate materials for the tunnel barrier in SDT junctions.

  6. Processing and Mechanical Properties of Directionally Solidified NiAl/NiAlTa Alloys

    NASA Technical Reports Server (NTRS)

    Johnson, D. R.; Oliver, B. F.; Noebe, R. D.; Whittenberger, J. D.

    1994-01-01

    Promising creep strengths were found for a directionally solidified NiAl-NiAlTa alloy when compared to other NiAl based intermetallics. The directionally solidified alloy had an off-eutectic composition that resulted in microstructures consisting of NiAl dendrites surrounded by aligned eutectic regions. The room temperature toughness of the two phase alloy was similar to that of polycrystalline NiAl even with the presence of the brittle Laves phase NiAlTa. Alloying additions that may improve the room temperature toughness by producing multiphase alloys are discussed.

  7. Atomic structure and oxygen deficiency of the ultrathin aluminium oxide barrier in Al/AlOx/Al Josephson junctions

    NASA Astrophysics Data System (ADS)

    Zeng, Lunjie; Tran, Dung Trung; Tai, Cheuk-Wai; Svensson, Gunnar; Olsson, Eva

    2016-07-01

    Al/AlOx/Al Josephson junctions are the building blocks of a wide range of superconducting quantum devices that are key elements for quantum computers, extremely sensitive magnetometers and radiation detectors. The properties of the junctions and the superconducting quantum devices are determined by the atomic structure of the tunnel barrier. The nanoscale dimension and disordered nature of the barrier oxide have been challenges for the direct experimental investigation of the atomic structure of the tunnel barrier. Here we show that the miniaturized dimension of the barrier and the interfacial interaction between crystalline Al and amorphous AlOx give rise to oxygen deficiency at the metal/oxide interfaces. In the interior of the barrier, the oxide resembles the atomic structure of bulk aluminium oxide. Atomic defects such as oxygen vacancies at the interfaces can be the origin of the two-level systems and contribute to decoherence and noise in superconducting quantum circuits.

  8. Atomic structure and oxygen deficiency of the ultrathin aluminium oxide barrier in Al/AlOx/Al Josephson junctions.

    PubMed

    Zeng, Lunjie; Tran, Dung Trung; Tai, Cheuk-Wai; Svensson, Gunnar; Olsson, Eva

    2016-07-12

    Al/AlOx/Al Josephson junctions are the building blocks of a wide range of superconducting quantum devices that are key elements for quantum computers, extremely sensitive magnetometers and radiation detectors. The properties of the junctions and the superconducting quantum devices are determined by the atomic structure of the tunnel barrier. The nanoscale dimension and disordered nature of the barrier oxide have been challenges for the direct experimental investigation of the atomic structure of the tunnel barrier. Here we show that the miniaturized dimension of the barrier and the interfacial interaction between crystalline Al and amorphous AlOx give rise to oxygen deficiency at the metal/oxide interfaces. In the interior of the barrier, the oxide resembles the atomic structure of bulk aluminium oxide. Atomic defects such as oxygen vacancies at the interfaces can be the origin of the two-level systems and contribute to decoherence and noise in superconducting quantum circuits.

  9. Atomic structure and oxygen deficiency of the ultrathin aluminium oxide barrier in Al/AlOx/Al Josephson junctions

    PubMed Central

    Zeng, Lunjie; Tran, Dung Trung; Tai, Cheuk-Wai; Svensson, Gunnar; Olsson, Eva

    2016-01-01

    Al/AlOx/Al Josephson junctions are the building blocks of a wide range of superconducting quantum devices that are key elements for quantum computers, extremely sensitive magnetometers and radiation detectors. The properties of the junctions and the superconducting quantum devices are determined by the atomic structure of the tunnel barrier. The nanoscale dimension and disordered nature of the barrier oxide have been challenges for the direct experimental investigation of the atomic structure of the tunnel barrier. Here we show that the miniaturized dimension of the barrier and the interfacial interaction between crystalline Al and amorphous AlOx give rise to oxygen deficiency at the metal/oxide interfaces. In the interior of the barrier, the oxide resembles the atomic structure of bulk aluminium oxide. Atomic defects such as oxygen vacancies at the interfaces can be the origin of the two-level systems and contribute to decoherence and noise in superconducting quantum circuits. PMID:27403611

  10. Effects of renal impairment on aluminum (Al) kinetics and Al-induced toxicity

    SciTech Connect

    Yokel, R.A.; McNamara, P.J.

    1986-03-01

    Al-induced toxicity most commonly occurs in the renally impaired. To study the influence of renal impairment on Al kinetics and toxicity, renally impaired rabbits were prepared by the remnant kidney procedure. Six weeks after partial nephrectomy creatinine clearance was 21% of controls and serum creatinine, BUN, Ca, and PO/sub 4/ were 222, 248, 122, and 50% of presurgery levels respectively. Serum Al kinetics after i.v. Al were: Al clearance 27%, initial and steady state volumes of distribution 50 and 80%, half life 362% and mean residence time 300% of controls (renally intact rabbits). Beginning 9 weeks after partial nephrectomy, rabbits received 145 to 160 ..mu..mole Al/kg s.c. daily, 5 x weekly x 4 weeks. Acquisition of a classically conditioned reflex (nictitating membrane extension) was impaired comparable to that produced by 100-200 ..mu..mole Al in controls but retention and extinction deficits were greater than those seen after 400 ..mu..mole Al in controls. Tissue Al concentrations were less than those seen after 200 ..mu..mole Al in controls. Body weight was comparable to that produced by 400 ..mu..mole Al in controls. These results suggest that renal impairment alters Al serum distribution, impairs its clearance, and increases the Al-induced impairment of memory and body weight gain.

  11. Influence of AlN thickness on AlGaN epilayer grown by MOCVD

    NASA Astrophysics Data System (ADS)

    Jayasakthi, M.; Juillaguet, S.; Peyre, H.; Konczewicz, L.; Baskar, K.; Contreras, S.

    2016-10-01

    AlGaN/AlN layers were grown by metalorganic chemical vapor deposition (MOCVD) on sapphire substrates. The AlN buffer thickness was varied from 400 nm to 800 nm. The AlGaN layer thickness was 1000 nm. The crystalline quality, thickness and composition of AlGaN were determined using high resolution X-ray diffraction (HRXRD). The threading dislocation density (TDD) was found to decrease with increase of AlN layer thickness. Reciprocal space mapping (RSM) was used to estimate the strain and relaxation between AlGaN and AlN. The optical properties of AlGaN layers were investigated by temperature dependent photoluminescence (PL). PL intensities of AlGaN layers increases with increasing the AlN thickness. The surface morphology of AlGaN was studied by atomic force microscopy (AFM). Root mean square (RMS) roughness values were found to be decreased while increase of AlN thickness.

  12. Durability Assessment of TiAl Alloys

    NASA Technical Reports Server (NTRS)

    Draper, Susan L.; Lerch, Bradley A.

    2008-01-01

    The durability of TiAl is a prime concern for the implementation of TiAl into aerospace engines. Two durability issues, the effect of high temperature exposure on mechanical properties and impact resistance, have been investigated and the results are summarized in this paper. Exposure to elevated temperatures has been shown to be detrimental to the room temperature ductility of gamma alloys with the most likely mechanisms being the ingress of interstitials from the surface. Fluorine ion implantation has been shown to improve the oxidation resistance of gamma alloys, and ideally it could also improve the environmental embrittlement of high Nb content TiAl alloys. The effect of F ion implantation on the surface oxidation and embrittlement of a third generation, high Nb content TiAl alloy (Ti-45Al-5Nb-B-C) were investigated. Additionally, the ballistic impact resistance of a variety of gamma alloys, including Ti-48Al-2Cr- 2Nb, Ti-47Al-2Cr-2Nb, ABB-2, ABB-23, NCG359E, 95A and Ti-45Al-5Nb-B-C was accessed. Differences in the ballistic impact properties of the various alloys will be discussed, particularly with respect to their manufacturing process, microstructure, and tensile properties.

  13. Diana Al-Hadid: Identity and Heritage

    ERIC Educational Resources Information Center

    Jungerberg, Tom; Smith, Anna; Borsh, Colleen

    2012-01-01

    Diana Al-Hadid's sculptures reflect the many locations, cultures, histories, and mythologies that have shaped her as an artist. In large-scale works which have the appearance of architectural ruins, Al-Hadid employs imagery drawn from many diverse interests including science and technology, history, and literature. She also incorporates images and…

  14. Sporadic and hereditary amyotrophic lateral sclerosis (ALS).

    PubMed

    Ajroud-Driss, Senda; Siddique, Teepu

    2015-04-01

    Genetic discoveries in ALS have a significant impact on deciphering molecular mechanisms of motor neuron degeneration. The identification of SOD1 as the first genetic cause of ALS led to the engineering of the SOD1 mouse, the backbone of ALS research, and set the stage for future genetic breakthroughs. In addition, careful analysis of ALS pathology added valuable pieces to the ALS puzzle. From this joint effort, major pathogenic pathways emerged. Whereas the study of TDP43, FUS and C9ORF72 pointed to the possible involvement of RNA biology in motor neuron survival, recent work on P62 and UBQLN2 refocused research on protein degradation pathways. Despite all these efforts, the etiology of most cases of sporadic ALS remains elusive. Newly acquired genomic tools now allow the identification of genetic and epigenetic factors that can either increase ALS risk or modulate disease phenotype. These developments will certainly allow for better disease modeling to identify novel therapeutic targets for ALS. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.

  15. Energetics of Al13 Keggin cluster compounds

    PubMed Central

    Armstrong, Christopher R.; Casey, William H.; Navrotsky, Alexandra

    2011-01-01

    The ϵ-Al13 Keggin aluminum hydroxide clusters are essential models in establishing molecular pathways for geochemical reactions. Enthalpies of formation are reported for two salts of aluminum centered ϵ-Keggin clusters, Al13 selenate, (Na(AlO4)Al12(OH)24(SeO4)4•12H2O) and Al13 sulfate, (NaAlO4Al12(OH)24(SO4)4•12H2O). The measured enthalpies of solution, ΔHsol, at 28 °C in 5 N HCl for the ε-Al13 selenate and sulfate are −924.57 (± 3.83) and −944.30 ( ± 5.66) kJ·mol-1, respectively. The enthalpies of formation from the elements, ΔHf,el, for Al13 selenate and sulfate are −19,656.35 ( ± 67.30) kJ·mol-1, and −20,892.39 ( ± 70.01) kJ·mol-1, respectively. In addition, ΔHf,el for sodium selenate decahydrate was calculated using data from high temperature oxide melt solution calorimetry measurements: −4,006.39 ( ± 11.91) kJ·mol-1. The formation of both ε-Al13 Keggin cluster compounds is exothermic from oxide-based components but energetically unfavorable with respect to a gibbsite-based assemblage. To understand the relative affinity of the ϵ-Keggin clusters for selenate and sulfate, the enthalpy associated with two S-Se exchange reactions was calculated. In the solid state, selenium is favored in the Al13 compound relative to the binary chalcogenate, while in 5 N HCl, sulfur is energetically favored in the cluster compound compared to the aqueous solution. This contribution represents the first thermodynamic study of ε-Al13 cluster compounds and establishes a method for other such molecules, including the substituted versions that have been created for kinetic studies. Underscoring the importance of ε-Al13 clusters in natural and anthropogenic systems, these data provide conclusive thermodynamic evidence that the Al13 Keggin cluster is a crucial intermediate species in the formation pathway from aqueous aluminum monomers to aluminum hydroxide precipitates. PMID:21852572

  16. Dose-enhancement effects in TaSi/Al- and Al-gate MOS devices

    SciTech Connect

    Fleetwood, D.M.; Beutler, D.E.; Draper, B.L.; Knott, D.; Brown, D.B.; Rosenstock, H.

    1988-01-01

    The response of MOS capacitors with TaSi/Al and Al electrodes to medium- and low-energy x-irradiation is investigated. Experimentally measured dose-enhancement effects are compared with computer simulations for these structures.

  17. Phase stability in binary Ti-Al

    NASA Technical Reports Server (NTRS)

    Anderson, C. D.; Hofmeister, W. H.; Bayuzick, R. J.

    1991-01-01

    Binary Ti-Al samples containing from 46 to 54 at. pct Al were solidified while undercooled by various amounts using electromagnetic levitation techniques. A detailed thermal history of these samples was obtained with sampling rates as high as 500 KHz during recalescence. This very high sampling rate was essential to resolve the thermal events. Primary alpha solidification was observed in samples containing from 51 to 54 at. pct Al that were undercooled less than about 100 K at solidification. Primary beta solidification was found for all undercoolings tested in samples containing less than 51 at. pct Al and for undercoolings greater than about 100 K in samples containing 51 to 54 at. pct Al.

  18. The neuropathology of FTD associated With ALS.

    PubMed

    Mackenzie, Ian R A

    2007-01-01

    There is increasing recognition of a clinical overlap between frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Recent advances in our understanding of the neuropathologic, biochemical, and genetic basis of these conditions provides evidence for a common underlying pathogenesis. The neuropathology in most cases of FTD with ALS is a subtype of frontotemporal lobar degeneration, characterized by neuronal inclusions that are immunoreactive for ubiquitin but not tau (frontotemporal lobar degeneration with ubiquitinated inclusions). These cases show significant pathologic overlap with clinically pure FTD and those with classic ALS. Moreover, the ubiquitinated pathologic protein in all these conditions has recently been identified as TDP-43. A number of families have been reported with autosomal dominant FTD-ALS linked to chromosome 9p and these also have TDP-43-positive frontotemporal lobar degeneration with ubiquitinated inclusions pathology. Together, these findings suggest that FTD-ALS is part of a clinicopathologic spectrum of disease, now identified as TDP-43 proteinopathies.

  19. NiAl alloys for structural uses

    NASA Technical Reports Server (NTRS)

    Koss, D. A.

    1991-01-01

    Alloys based on the intermetallic compound NiAl are of technological interest as high temperature structural alloys. These alloys possess a relatively low density, high melting temperature, good thermal conductivity, and (usually) good oxidation resistance. However, NiAl and NiAl-base alloys suffer from poor fracture resistance at low temperatures as well as inadequate creep strength at elevated temperatures. This research program explored macroalloying additions to NiAl-base alloys in order to identify possible alloying and processing routes which promote both low temperature fracture toughness and high temperature strength. Initial results from the study examined the additions of Fe, Co, and Hf on the microstructure, deformation, and fracture resistance of NiAl-based alloys. Of significance were the observations that the presence of the gamma-prime phase, based on Ni3Al, could enhance the fracture resistance if the gamma-prime were present as a continuous grain boundary film or 'necklace'; and the Ni-35Al-20Fe alloy was ductile in ribbon form despite a microstructure consisting solely of the B2 beta phase based on NiAl. The ductility inherent in the Ni-35Al-20Fe alloy was explored further in subsequent studies. Those results confirm the presence of ductility in the Ni-35Al-20Fe alloy after rapid cooling from 750 - 1000 C. However exposure at 550 C caused embrittlement; this was associated with an age-hardening reaction caused by the formation of Fe-rich precipitates. In contrast, to the Ni-35Al-20Fe alloy, exploratory research indicated that compositions in the range of Ni-35Al-12Fe retain the ordered B2 structure of NiAl, are ductile, and do not age-harden or embrittle after thermal exposure. Thus, our recent efforts have focused on the behavior of the Ni-35Al-12Fe alloy. A second parallel effort initiated in this program was to use an alternate processing technique, mechanical alloying, to improve the properties of NiAl-alloys. Mechanical alloying in the

  20. Photoelectrical, photophysical and photocatalytic properties of Al based MOFs: MIL-53(Al) and MIL-53-NH{sub 2}(Al)

    SciTech Connect

    An, Yang; Li, Huiliang; Liu, Yuanyuan; Huang, Baibiao; Sun, Qilong; Dai, Ying; Qin, Xiaoyan; Zhang, Xiaoyang

    2016-01-15

    Two Al based MOFs (MIL-53(Al) and MIL-53-NH{sub 2} (Al)) were synthesized, and their photoelectrical, photophysical and photocatalytic properties towards oxygen evolution from water were investigated. Different from the ligand to metal charge transfer process previously reported, we proposes a new photocatalytic mechanism based on electron tunneling according to the results of theoretical calculation, steady state and time resolved fluorescence spectra. The organic linkers absorb photons, giving rise to electrons and holes. Then, the photogenerated electrons tunnel through the AlO{sub 6}-octahedra, which not only inhibit the recombination of photogenerated charge carriers, but also is a key factor to the photocatalytic activity of Al based MOFs. - Graphical abstract: The photoelectrical, photophysical and photocatalytic properties towards oxygen evolution from water of two Al based MOFs were investigated. A new photocatalytic mechanism was proposed based on electron tunneling according to the results of both theoretical calculation and steady state, time resolved fluorescence spectra. The electron tunneling process not only inhibit the recombination of photogenerated charge carriers, but also is a key factor to the photocatalytic activity of Al based MOFs.

  1. Al/Al2O3 Metal Matrix Composites (MMCs) and Macrocomposites for Armor Applications

    DTIC Science & Technology

    2013-09-01

    ceramics (high hardness, high stiffness, low thermal expansion). In this study , Al/Al2O3 MMCs with alumina particle contents ranging from 12% to 46% were...expansion). In this study , Al/Al2O3 MMCs with alumina particle contents ranging from 12% to 46% were fabricated by different processing approaches...the different MMCs. The matrix alloy, alumina volume fraction, densities, mechanical properties , and thermal properties are summarized in Table 2

  2. High temperature creep behaviour of Al-rich Ti-Al alloys

    NASA Astrophysics Data System (ADS)

    Sturm, D.; Heilmaier, M.; Saage, H.; Aguilar, J.; Schmitz, G. J.; Drevermann, A.; Palm, M.; Stein, F.; Engberding, N.; Kelm, K.; Irsen, S.

    2010-07-01

    Compared to Ti-rich γ-TiAl-based alloys Al-rich Ti-Al alloys offer an additional reduction of in density and a better oxidation resistance which are both due to the increased Al content. Polycrystalline material was manufactured by centrifugal casting. Microstructural characterization was carried out employing light-optical, scanning and transmission electron microscopy and XRD analyses. The high temperature creep of two binary alloys, namely Al60Ti40 and Al62Ti38 was comparatively assessed with compression tests at constant true stress in a temperature range between 1173 and 1323 K in air. The alloys were tested in the cast condition (containing various amounts of the metastable phases Al5Ti3 and h-Al2Ti) and after annealing at 1223 K for 200 h which produced (thermodynamically stable) lamellar γ-TiAl + r-Al2Ti microstructures. In general, already the as-cast alloys exhibit a reasonable creep resistance at 1173 K. Compared with Al60Ti40, both, the as-cast and the annealed Al62Ti38 alloy exhibit better creep resistance up to 1323 K which can be rationalized by the reduced lamella spacing. The assessment of creep tests conducted at identical stress levels and varying temperatures yielded apparent activation energies for creep of Q = 430 kJ/mol for the annealed Al60Ti40 alloy and of Q = 383 kJ/mol for the annealed Al62Ti38 material. The latter coincides well with that of Al diffusion in γ-TiAl, whereas the former can be rationalized by the instability of the microstructure containing metastable phases.

  3. Corrosion Studies of 2195 Al-Li Alloy and 2219 Al Alloy with Differing Surface Treatments

    NASA Technical Reports Server (NTRS)

    Danford, M. D.; Mendrek, M. J.

    1998-01-01

    Corrosion studies of 2195 Al-Li and 2219 Al alloys have been conducted using the scanning reference electrode technique (SRET) and the polarization resistance (PR) technique. The SRET was used to study corrosion mechanisms, while corrosion rate measurements were studied with the PR technique. Plates of Al203 blasted, soda blasted and conversion coated 2219 Al were coated with Deft primer and the corrosion rates studied with the EIS technique. Results from all of these studies are presented.

  4. Japanese version of the ALS-FTD-Questionnaire (ALS-FTD-Q-J).

    PubMed

    Watanabe, Yasuhiro; Beeldman, Emma; Raaphorst, Joost; Izumi, Yuishin; Yoshino, Hiide; Masuda, Michihito; Atsuta, Naoki; Ito, Satoru; Adachi, Tadashi; Adachi, Yoshiki; Yokota, Osamu; Oda, Masaya; Hanashima, Ritsuko; Ogino, Mieko; Ichikawa, Hiroo; Hasegawa, Kazuko; Kimura, Hideki; Shimizu, Toshio; Aiba, Ikuko; Yabe, Hayato; Kanba, Makoto; Kusumi, Kimiyoshi; Aoki, Tetsuya; Hiroe, Yu; Watanabe, Hirohisa; Nishiyama, Kazutoshi; Nomoto, Masahiro; Sobue, Gen; Nakashima, Kenji

    2016-08-15

    Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share common clinical, genetic and neuropathological features. Some ALS patients have behavioral/personality changes, which could result in significant obstacles in the care provided by family members and caregivers. An easy screening tool would contribute greatly to the evaluation of these symptoms. We translated the ALS-FTD-Questionnaire, developed in the Netherlands, into Japanese (ALS-FTD-Q-J) and examined the clinimetric properties (internal consistency, construct and clinical validity). Patients with ALS and/or behavioral variant FTD (bvFTD) were evaluated alongside healthy controls in this multicenter study. All ALS patients, regardless of bvFTD status, were further evaluated by the frontal behavioral inventory (FBI) and for frontal/executive function, cognition, anxiety/depression, and motor functions. Data from 146 subjects were analyzed: ALS (92), ALS-bvFTD (6), bvFTD (16), and healthy controls (32). The internal consistency of the ALS-FTD-Q-J was good (Cronbach α=0.92). The ALS-FTD-Q-J showed construct validity as it exhibited a high correlation with the FBI (r=0.79). However, correlations were moderate with anxiety/depression and low with cognitive scales, in contrast to the original report, i.e. a moderate correlation with cognition and a low correlation with anxiety/depression. The ALS-FTD-Q-J discriminated ALS patients from (ALS-)bvFTD patients and controls. Thus, the ALS-FTD-Q-J is useful for evaluating Japanese ALS/FTD patients.

  5. Alanes formation on the Al(111) surface

    NASA Astrophysics Data System (ADS)

    Rangan, Sylvie; Veyan, Jean-Francois; Chabal, Yves J.; Chaudhuri, Santanu; Muckerman, James T.

    2008-03-01

    Alane clusters (AlxHy) are believed to be the ubiquitous intermediates in hydrogen storage reactions for a wide variety of alanates (LiAlH4, NaAlH4) currently considered for hydrogen storage. The formation and behavior of alanes at surfaces appear to control and limit the efficiency of hydrogen storage. In particular, hydrogen adsorption on the Al(111) surface leads to the coexistence of several adsorbed species, the concentration of which is affected by the step density, the surface coverage and the temperature. We combine density functional theory (DFT) and surface infra-red (IR) absorption spectroscopy to uncover the mechanisms for alane formation on Al(111) surfaces. At low coverage, DFT predicts a two-fold bridge site adsorption for atomic hydrogen, consistent with previous Electron Energy Loss Spectroscopy measurements. At higher coverage, the formation of small chemisorbed AlH3 occurs at the step edges. With increasing coverage AlH3 is extracted from the step edge and becomes highly mobile on the terraces in a weakly bound state. This mobility is the key factor leading to the growth of larger alanes through AlH3 oligomerization. For these large alanes, previous Thermal Programmed Desorption studies are discussed and compared to the thermal stability observed in IR.

  6. Effects of hydrogen absorption in TbNiAl and UNiAl

    SciTech Connect

    Bordallo, H.N.; Nakotte, H.; Schultz, A.; Kolomiets, A.V.; Havela, L.; Andreev, A.V.

    1998-12-31

    Although hydrides of intermetallic compounds are used extensively as hydrogen-storage media, little is known about the exact nature of metal-hydrogen interactions. However, this knowledge is of essential importance for the understanding of thermodynamics and other properties. Hydrides (deuterides) of TbNiAl and UNiAl have been widely studied because of drastic increase of magnetic ordering temperature under hydrogenation. Here the authors report neutron-diffraction results of the three deuterides, TbNiAlD{sub 1.28}, TbNiAlD{sub 0.8}a nd UNiAlD{sub 2.23}.

  7. Phase diagrams of Al-Si and Al-Ge systems

    NASA Astrophysics Data System (ADS)

    Kagaya, Hiroko-Matsuo; Imazawa, Kazumoto; Sato, Mayumi; Soma, Toshinobu

    1998-03-01

    Considering the contributions from the band and local mode frequencies, the temperature- and pressure-dependent mean-square displacement for Al-Si and Al-Ge solid solutions is quantitatively calculated to be similar to that for matrix Al. Then, the concentration-dependence of the Debye temperature at higher and lower temperatures is estimated, the pressure effect on the solidus curve is presented by applying Lindeman's melting law to the Al-Si and Al-Ge alloy systems. The solidus curve obtained increases as a function of the pressure, and is in good agreement with the observed tendency for these solid solutions.

  8. A new discontinuously reinforced aluminum MMC: Al+AlB{sub 2} flakes

    SciTech Connect

    HALL,AARON C.; ECONOMY,J.

    2000-06-08

    Development of a novel metal matrix composite based on the Al-B alloy system has been undertaken. Preparation of this discontinuously reinforced material is based on the precipitation of high aspect ratio AlB{sub 2} from an Al-B alloy. This paper describes a number of efforts forced on preparing high volume fractions (> 30 v%) of AlB{sub 2} in aluminum. New insights into the behavior of the Al-B alloys system allowed this effort to be successful.

  9. Atomistic Modeling of RuAl and (RuNi) Al Alloys

    NASA Technical Reports Server (NTRS)

    Gargano, Pablo; Mosca, Hugo; Bozzolo, Guillermo; Noebe, Ronald D.; Gray, Hugh R. (Technical Monitor)

    2002-01-01

    Atomistic modeling of RuAl and RuAlNi alloys, using the BFS (Bozzolo-Ferrante-Smith) method for alloys is performed. The lattice parameter and energy of formation of B2 RuAl as a function of stoichiometry and the lattice parameter of (Ru(sub 50-x)Ni(sub x)Al(sub 50)) alloys as a function of Ni concentration are computed. BFS based Monte Carlo simulations indicate that compositions close to Ru25Ni25Al50 are single phase with no obvious evidence of a miscibility gap and separation of the individual B2 phases.

  10. Decoding ALS: from genes to mechanism.

    PubMed

    Taylor, J Paul; Brown, Robert H; Cleveland, Don W

    2016-11-10

    Amyotrophic lateral sclerosis (ALS) is a progressive and uniformly fatal neurodegenerative disease. A plethora of genetic factors have been identified that drive the degeneration of motor neurons in ALS, increase susceptibility to the disease or influence the rate of its progression. Emerging themes include dysfunction in RNA metabolism and protein homeostasis, with specific defects in nucleocytoplasmic trafficking, the induction of stress at the endoplasmic reticulum and impaired dynamics of ribonucleoprotein bodies such as RNA granules that assemble through liquid-liquid phase separation. Extraordinary progress in understanding the biology of ALS provides new reasons for optimism that meaningful therapies will be identified.

  11. Ni{sub 3}Al aluminide alloys

    SciTech Connect

    Liu, C.T.

    1993-10-01

    This paper provides a brief review of the recent progress in research and development of Ni{sub 3}Al and its alloys. Emphasis has been placed on understanding low ductility and brittle fracture of Ni{sub 3}Al alloys at ambient and elevated temperatures. Recent studies have resulted in identifying both intrinsic and extrinsic factors governing the fracture behavior of Ni{sub 3}Al alloys. Parallel efforts on alloy design using physical metallurgy principles have led to properties for structural use. Industrial interest in these alloys is high, and examples of industrial involvement in processing and utilization of these alloys are briefly mentioned.

  12. Arsenate uptake by Al nanoclusters and other Al-based sorbents during water treatment.

    PubMed

    Mertens, Jasmin; Rose, Jérôme; Wehrli, Bernhard; Furrer, Gerhard

    2016-01-01

    In many parts of the world, arsenic from geogenic and anthropogenic sources deteriorates the quality of drinking water resources. Effective methods of arsenic removal include adsorption and coagulation with iron- and aluminum-based materials, of which polyaluminum chloride is widely employed as coagulant in water treatment due to its low cost and high efficiency. We compared the arsenic uptake capacity and the arsenic bonding sites of different Al-based sorbents, including Al nanoclusters, polyaluminum chloride, polyaluminum granulate, and gibbsite. Extended X-ray absorption fine structure (EXAFS) spectroscopy revealed that As(V) forms bidentate-binuclear complexes in interaction with all Al-based removal agents. The octahedral configuration of nanoclusters and the distribution of sorption sites remain the same in all types of removal agents consisting of nano-scale Al oxyhydroxide particles. The obtained distances for As(V)-O and As(V)-Al agreed with previously published data and were found to be 1.69 ± 0.02 Å and 3.17-3.21 Å, respectively. Our study suggests that As(V) binds to Al nanoclusters as strongly as to Al oxide surfaces. The As sorption capacity of Al nanoclusters was found to be very similar to that of Al clusters in a polyaluminum chloride. The most efficient Al-based sorbents for arsenic removal were Al nanoclusters, followed by polyaluminum granulate.

  13. InAlN/AlN/GaN heterostructures for high electron mobility transistors

    NASA Astrophysics Data System (ADS)

    Usov, S. O.; Sakharov, A. V.; Tsatsulnikov, A. F.; Lundin, V. W.; Zavarin, E. E.; Nikolaev, A. E.; Yagovkina, M. A.; Zemlyakov, V. E.; Egorkin, V. I.; Ustinov, V. M.

    2016-08-01

    The results of development of InAlN/AlN/GaN heterostructures, grown on sapphire substrates by metal-organic chemical vapour deposition, and high electron mobility transistors (HEMTs) based on them are presented. The dependencies of the InAlN/AlN/GaN heterostructure properties on epitaxial growth conditions were investigated. The optimal indium content and InAlN barrier layer thicknesses of the heterostructures for HEMT s were determined. The possibility to improve the characteristics of HEMTs by in-situ passivation by Si3N4 thin protective layer deposited in the same epitaxial process was demonstrated. The InAlN/AlN/GaN heterostructure grown on sapphire substrate with diameter of 100 mm were obtained with sufficiently uniform distribution of sheet resistance. The HEMTs with saturation current of 1600 mA/mm and transconductance of 230 mS/mm are demonstrated.

  14. Oxidation of Al2O3 continuous fiber-reinforced/NiAl composites

    NASA Technical Reports Server (NTRS)

    Doychak, J.; Nesbitt, J. A.; Noebe, R. D.; Bowman, R. R.

    1992-01-01

    The 1200 C and 1300 C isothermal and cyclic oxidation behavior of Al2O3 continuous fiber-reinforced/NiAl composites were studied. Oxidation resulted in formation of Al2O3 external scales in a similar manner as scales formed on monolithic NiAl. The isothermal oxidation of an Al2O3/NiAl composite resulted in oxidation of the matrix along the fiber/matrix interface near the fiber ends. This oxide acted as a wedge between the fiber and the matrix, and, under cyclic oxidation conditions, led to further oxidation along the fiber lengths and eventual cracking of the composite. The oxidation behavior of composites in which the Al2O3 fibers were sputter coated with nickel prior to processing was much more severe. This was attributed to open channels around the fibers which formed during processing, most likely as a result of the diffusion of the nickel coating into the matrix.

  15. Elimination of AlGaN epilayer cracking by spatially patterned AlN mask

    NASA Astrophysics Data System (ADS)

    Sarzyński, Marcin; Kryśko, Marcin; Targowski, Grzegorz; Czernecki, Robert; Sarzyńska, Agnieszka; Libura, Adam; Krupczyński, Wiktor; Perlin, Piotr; Leszczyński, Michał

    2006-03-01

    The inherent problem in III-nitride technology is the cracking of AlGaN layers that results from lattice mismatch between AlGaN and GaN. In case of thin substrates (30-90μm), such as, bulk GaN grown by the high-pressure/high-temperature method, the bowing of AlGaN /GaN strained structures becomes an additional problem. To eliminate cracking and bowing, AlGaN layers were grown on GaN substrates with an AlN mask patterned to form 3-15μm wide windows. In the 3μm window, the AlGaN layer was not cracked, although its thickness and Al composition exceeded critical values for growth on nonpatterned substrates. Dislocation density in the windows was of 5×106/cm2.

  16. Diffusion at the Al/Al oxide interface during electromigration in wide lines

    NASA Astrophysics Data System (ADS)

    Augur, R. A.; Wolters, R. A. M.; Schmidt, W.; Dirks, A. G.; Kordić, S.

    1996-03-01

    Significant large-scale modification of the surface of Al-Si conductors was observed, due to electromigration in wide lines and under low stress conditions. After electromigration stressing the Al layers showed local thickness variations, i.e., damage by thinning. The mechanism underlying this damage causes substantial metal transport. Nevertheless, damage by thinning has received little attention in the past. Thinning was observed: (1) in a number of different alloys (Al-Si, Al-Cu, Al-Si-V, and Al-Si-V-Pd), (2) with a number of different underlayers [SiO2, W-Ti (no vacuum break after Al deposition) and W-Ti (oxidized surface before Al deposition)], (3) over an extended temperature range, (4) over a range of current density, and (5) in structures with and without passivation. The results show that thinning is a general phenomenon. An activation energy of approximately 0.5 eV was determined for the temperature dependence of a combined mechanism of concurrent thinning plus voiding in Al99Si1. Several alternatives are examined to explain the observations, namely mass movement along dislocations, Al bulk diffusion, and diffusion at the interface between the Al and its oxide. It is shown that diffusion at the Al/Al oxide interface most probably plays an important role in the damage mechanism, even under stress conditions where grain boundary diffusion is traditionally thought to dominate. Results also showed that alloying of Al with Pd can reduce the effects of damage by thinning.

  17. Interdiffusion in Diffusion Couples: U-Mo v. Al and Al-Si

    SciTech Connect

    D. D. Keiser, Jr.; E. Perez; B. Yao; Y. H. Sohn

    2009-11-01

    Interdiffusion and microstructural development in the U-Mo-Al system was examined using solid-tosolid diffusion couples consisting of U-7wt.%Mo, U-10wt.%Mo and U-12wt.%Mo vs. pure Al, annealed at 600°C for 24 hours. The influence of Si alloying addition (up to 5 wt.%) in Al on the interdiffusion microstructural development was also examined using solid-to-solid diffusion couples consisting of U-7wt.%Mo, U-10wt.%Mo and U-12wt.%Mo vs. pure Al, Al-2wt.%Si, and Al-5wt.%Si annealed at 550°C up to 20 hours. Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and electron probe microanalysis (EPMA) were employed to examine the development of a very fine multiphase intermetallic layer. In ternary U-Mo-Al diffusion couples annealed at 600°C for 24 hours, interdiffusion microstructure varied of finely dispersed UAl3, UAl4, U6Mo4Al43, and UMo2Al20 phases while the average composition throughout the interdiffusion zone remained constant at approximately 80 at.% Al. Interdiffusion microstructure observed by SEM/TEM analyses and diffusion paths drawn from concentration profiles determined by EPMA appear to deviate from the assumption of “local thermodynamic equilibrium,” and suggest that interdiffusion occurs via supersaturated UAl4 followed by equilibrium transformation into UAl3, U6Mo4Al43, UAl4 and UMo2Al20 phases. Similar observation was made for U-Mo vs. Al diffusion couples annealed at 550°C. The addition of Si (up to 5 wt.%) in Al significantly reduced the thickness of the intermetallic layer by changing the constituent phases of the interdiffusion zone developed in U-Mo vs. Al-Si diffusion couples. Specifically, the formation of (U,Mo)(Al,Si)3 with relatively large solubility for Mo and Si, along with UMo2Al20 phases was observed along with disappearance of U6Mo4Al43 and UAl4 phases. Simplified understanding based on U-Al, U-Si, and Mo-Si binary phase diagrams is discussed in the light of the beneficial effect of Si alloying addition.

  18. On Dobbert et al, 'Cultural Transmission...'

    ERIC Educational Resources Information Center

    Gearing, Frederick

    1984-01-01

    Criticizes Dobbert et al's model of cultural transmission (presented in earlier article) as being a species of social physics. Suggests improvements to the model, notably that observation and analysis at the emic level be taken into account. (RDN)

  19. Pike International, LLC et al. Information Sheet

    EPA Pesticide Factsheets

    Pike International LLC, et al. (the Company) is located in New Haven, Connecticut. The Complaint involves the lease of, and renovation activities conducted at, property constructed prior to 1978, located in New Haven, Connecticut.

  20. ALS and Oxidative Stress: The Neurovascular Scenario

    PubMed Central

    Thakur, Keshav; Gupta, Pawan Kumar

    2013-01-01

    Oxidative stress and angiogenic factors have been placed as the prime focus of scientific investigations after an establishment of link between vascular endothelial growth factor promoter (VEGF), hypoxia, and amyotrophic lateral sclerosis (ALS) pathogenesis. Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter and mutant superoxide dismutase 1 (SOD1) which are characterised by atrophy and muscle weakness resulted in phenotype resembling human ALS in mice. This results in lower motor neurodegeneration thus establishing an important link between motor neuron degeneration, vasculature, and angiogenic molecules. In this review, we have presented human, animal, and in vitro studies which suggest that molecules like VEGF have a therapeutic, diagnostic, and prognostic potential in ALS. Involvement of vascular growth factors and hypoxia response elements also highlights the converging role of oxidative stress and neurovascular network for understanding and treatment of various neurodegenerative disorders like ALS. PMID:24367722

  1. 12th Annual ALS Users' Association Meeting

    SciTech Connect

    Robinson, Arthur L.

    1999-12-17

    Science took the front seat as 219 Advanced Light Source (ALS) users and staff gathered on Monday and Tuesday, October 18 and 19 for the twelfth annual users' meeting. The bulk of the meeting was dedicated to reports on science at the ALS. Packed into two busy days were 31 invited oral presentations and 80 submitted poster presentations, as well as time to visit 24 vendor booths. The oral sessions were dedicated to environmental science, chemical dynamics, biosciences, magnetic materials, and atomic and molecular science. In addition, there was an ALS highlights session that emphasized new results and a session comprising highlights from the young scientists who will carry the ALS into the future.

  2. Half life of /sup 26/Al

    SciTech Connect

    Norris, T.L.; Gancarz, A.J.; Rokop, D.J.; Thomas, K.W.

    1983-01-01

    The half-life of /sup 26/Al has been redetermined because of suggestions of an error in the accepted value based on its use in calculating /sup 21/Ne production rates from cosmic rays in meteorites. Two solutions of /sup 26/Al were analyzed for the specific radioactivity and mass spectrometric determination of the /sup 26/Al concentration. The half-life obtained for /sup 26/Al was 7.05 x 10/sup 5/ years +- 3.7% at the two sigma level. This is identical to the accepted value of 7.16 x 10/sup 5/ years and indicates that problems with the /sup 21/Ne production rate is not due to an erroneous half-life.

  3. Al Qaeda: A Modern Day Lernaean Hydra

    DTIC Science & Technology

    2010-03-01

    insurgency. Still others have referred to it as a netwar organization waging conflict primarily through the use of networks. A few authors have...organization waging conflict primarily through the use of networks. A few authors have characterized it as a religious movement. Like the Hydra, Al...Al Qaeda as an insurgency. Still others have referred to it as a Netwar organization waging conflict primarily through the use of networks.1 A

  4. Patterns of inheritance in familial ALS.

    PubMed

    Bradley, Marcus; Bradley, Lloyd; de Belleroche, Jackie; Orrell, Richard W

    2005-05-10

    We investigated 185 families with ALS for evidence of anticipation and mitochondrial inheritance. Although initial analysis demonstrated significant anticipation of age at death between generations in patients with familial ALS, further analysis demonstrated features of regression to the mean, suggesting that the perceived differences are the result of bias. In addition, there was no evidence of an effect of preferential maternal inheritance, which would have supported transmission of mitochondrial DNA mutations.

  5. 17th Annual ALS Users' Association Meeting

    SciTech Connect

    Robinson, Art; Tamura, Lori

    2004-11-29

    It's not exactly Russian roulette, but scheduling October events outdoors is not risk-free, even in usually sunny California. An overflow crowd of more than 400 registered users, ALS staff, and vendors enjoyed a full indoor program featuring science highlights and workshops spread over two and a half days from October 18 to October 20. However, a major storm, heralding the onset of the San Francisco Bay Area rainy season, posed a few weather challenges for the events on the ALS patio.

  6. Modeling of precipitation in Al alloys

    SciTech Connect

    Asta, M.; Foiles, S.M.; Wolfer, W.G.

    1996-10-01

    Objective was the development of a computational model of precipitation from a supersaturated alloy solid solution. The model is based on the formalism of chemical-reaction-rate theory combined with classical descriptions of precipitate thermodynamic properties and a mean-field treatment of diffusion-limited growht and coarsening. For the case of precipitation of Al{sub 3}Sc in supersaturated Al-Sc alloys, it is demonstrated how the model can be used to calculate number densities and size distributions of precipitates as a function of aging time and temperature, including effects of continuous cooling and thermally generated point defects. Application of the model to a specific alloy system requires knowledge of diffusion data, point defect energetics, and thermodynamic properties for bulk phases and interphase interfaces. For interfaces and point defects, thermodynamic data can be difficult to measure and reliable values of defect free energies are often unavailable. For this reason, part of the efforts were devoted to applying semiempirical and first-principles atomistic techniques to the calculation of interfacial and point-defect thermodynamic properties. This report discusses applications for interphase interfaces in the Al-Ag, Al-Sc, and Al-Li alloy systems. We also describe atomistic work aimed at understanding the energetics of vacancy clusters in Al. These clusters serve as sinks for isolated vacancies during aging and their growth can lead to more complex defects, such as dislocation loops, that act as heterogeneous nucleation sites.

  7. Theoretics-directed effect of copper or aluminum content on the ductility characteristics of Al-based (Al3Ti, AlTi, AlCu, AlTiCu2) intermetallic compounds

    NASA Astrophysics Data System (ADS)

    Li, Yong; Ma, Xiao-Juan; Liu, Qi-Jun; Kong, Ge-Xing; Ma, Hai-Xia; Wang, Wen-Peng; Wang, Yi-Gao; Jiao, Zhen; Liu, Fu-Sheng; Liu, Zheng-Tang

    2016-11-01

    First-principle simulations have been applied to investigate the effect of copper (Cu) or aluminum (Al) content on the ductility of Al3Ti, AlTi, AlCu, and AlTiCu2 alloys. The mechanical stable and elastic properties of Al-based intermetallic compounds are researched by density functional theory with the generalized gradient approximation (DFT-GGA). The calculated lattice constants are in conformity with the previous experimental and theoretical data. The deduced elastic constants show that the investigated Al3Ti, AlTi, AlCu, and AlTiCu2 structures are mechanically stable. Shear modulus, Young’s modulus, Poisson’s ratio, and the ratio B/G have also been figured out by using reckoned elastic constants. A further analysis of Young’s modulus and Poisson’s ratio reveals that the third added element copper content has significant effects on the Al-Ti-based ICs ductile character. Project supported by the National Natural Science Foundation of China (Grant Nos. 41674088, 11574254, 11272296, and 11547311), the National Basic Research Program of China (Grant No. 2011CB808201), the Fundamental Research Fund for the Central Universities, China (Grant Nos. 2682014ZT30 and 2682014ZT31), and the Fund of the State Key Laboratory of Solidification Processing in Northwestern Polytechnical University, China (Grant No. SKLSP201511).

  8. Metastability in the MgAl2O4-Al2O3 System

    DOE PAGES

    Wilkerson, Kelley R.; Smith, Jeffrey D.; Hemrick, James G.

    2014-07-22

    Aluminum oxide must take a spinel form ( γ-Al2O3) at elevated temperatures in order for extensive solid solution to form between MgAl2O4 and α-Al2O3. The solvus line between MgAl2O4 and Al2O3 has been defined at 79.6 wt% Al2O3 at 1500°C, 83.0 wt% Al2O3 at 1600°C, and 86.5 wt% Al2O3 at 1700°C. A metastable region has been defined at temperatures up to 1700°C which could have significant implications for material processing and properties. Additionally, initial processing could have major implications on final chemistry. The spinel solid solution region has been extended to form an infinite solid solution with Al2O3 at elevatedmore » temperatures. A minimum in melting at 1975°C and a chemistry of 96 wt% Al2O3 rather than a eutectic is present, resulting in no eutectic crystal formation during solidification.« less

  9. Temperature dependence of the dielectric response of anodized Al-Al2O3-metal capacitors

    NASA Astrophysics Data System (ADS)

    Hickmott, T. W.

    2003-03-01

    The temperature dependence of capacitance, CM, and conductance, GM, of Al-Al2O3-metal capacitors with Cu, Ag, and Au electrodes has been measured between 100 and 340 K at seven frequencies between 10 kHz and 1 MHz. Al2O3 films between 15 and 64 nm thick were formed by anodizing evaporated Al films in borate-glycol or borate-H2O electrolyte. The interface capacitance at the Al2O3-metal interface, CI, which is in series with the capacitance CD due to the Al2O3 dielectric, is determined from plots of 1/CM versus insulator thickness. CI is not fixed for a given metal-insulator interface but depends on the vacuum system used to deposit the metal electrode. CI is nearly temperature independent. When CI is taken into account the dielectric constant of Al2O3 determined from capacitance measurements is ˜8.3 at 295 K. The dielectric constant does not depend on anodizing electrolyte, insulator thickness, metal electrode, deposition conditions for the metal electrode or measurement frequency. By contrast, GM of Al-Al2O3-metal capacitors depends on both the deposition conditions of the metal and on the metal. For Al-Al2O3-Cu capacitors, GM is larger for capacitors with large values of 1/CI that result when Cu is evaporated in an oil-pumped vacuum system. For Al-Al2O3-Ag capacitors, GM does not depend on the Ag deposition conditions.

  10. Effects of Al(III) and nano-Al13 species on malate dehydrogenase activity.

    PubMed

    Yang, Xiaodi; Cai, Ling; Peng, Yu; Li, Huihui; Chen, Rong Fu; Shen, Ren Fang

    2011-01-01

    The effects of different aluminum species on malate dehydrogenase (MDH) activity were investigated by monitoring amperometric i-t curves for the oxidation of NADH at low overpotential using a functionalized multi-wall nanotube (MWNT) modified glass carbon electrode (GCE). The results showed that Al(III) and Al(13) can activate the enzymatic activity of MDH, and the activation reaches maximum levels as the Al(III) and Al(13) concentration increase. Our study also found that the effects of Al(III) and Al(13) on the activity of MDH depended on the pH value and aluminum speciation. Electrochemical and circular dichroism spectra methods were applied to study the effects of nano-sized aluminum compounds on biomolecules.

  11. Microscopic Properties of Long-Period Ordering in Al-Rich TiAl Alloys

    NASA Astrophysics Data System (ADS)

    Hata, S.; Nakano, T.; Kuwano, N.; Itakura, M.; Matsumura, S.; Umakoshi, Y.

    2008-07-01

    The ordering mechanism of long-period superstructures (LPSs) in Al-rich TiAl alloys has been investigated by high-resolution transmission electron microscopy (HRTEM). The LPSs are classified in terms of arrangements of base clusters with different shapes and compositions formed in Ti-rich (002) layers of L10-TiAl matrix: square Ti4Al, fat rhombus Ti3Al, and lean rhombus Ti2Al type clusters. The HRTEM observations revealed that antiphase boundaries of long-range-ordered LPS domains and short-range-ordered microdomains are constructed by various space-filling arrangements of the base clusters. Such a microscopic property characterized by the base clusters and their arrangements is markedly analogous to that of the {left< {{text{1,1/2,0}}} rightrangle } * special-point ordering alloys such as Ni-Mo.

  12. Effects of Al(III) and Nano-Al13 Species on Malate Dehydrogenase Activity

    PubMed Central

    Yang, Xiaodi; Cai, Ling; Peng, Yu; Li, Huihui; Chen, Rong Fu; Shen, Ren Fang

    2011-01-01

    The effects of different aluminum species on malate dehydrogenase (MDH) activity were investigated by monitoring amperometric i-t curves for the oxidation of NADH at low overpotential using a functionalized multi-wall nanotube (MWNT) modified glass carbon electrode (GCE). The results showed that Al(III) and Al13 can activate the enzymatic activity of MDH, and the activation reaches maximum levels as the Al(III) and Al13 concentration increase. Our study also found that the effects of Al(III) and Al13 on the activity of MDH depended on the pH value and aluminum speciation. Electrochemical and circular dichroism spectra methods were applied to study the effects of nano-sized aluminum compounds on biomolecules. PMID:22163924

  13. Protective Al2O3 scale formation on NbAl3-base alloys

    NASA Technical Reports Server (NTRS)

    Doychak, J.; Hebsur, M. G.

    1991-01-01

    The oxidation of NbAl3 with additions of Cr and Y was studied to determine the mechanisms of the beneficial effects of these elements upon oxidation. Cr additions to the binary NbAl3 alloy of up to 6.8 at. percent reduced the scale growth rates and promoted alpha-Al2O3 formation over much longer times relative to binary NbAl3. A major effect of Cr is to form a layer of AlNbCr at the metal/scale interface, which is inherently more oxidation-resistant than the matrix alloy in the long term. Yttrium additions to a Cr-containing alloy improved the scale growth rate and adherence and changed the scale microstructure to mimic that of a typical protective Al2O3 scale.

  14. Magnetic behavior of CoPt-AlN granular structure laminated with AlN layers

    NASA Astrophysics Data System (ADS)

    Yu, Youxing; Shi, Ji; Nakamura, Yoshio

    2011-04-01

    The magnetic behavior of CoPt-AlN granular structure laminated with AlN layers has been studied. Ultrathin multilayer structure, [CoPt0.5 nm/AlN0.5nm]4, is used as the precursor of the magnetic layers, which are separated by 5-nm-thick AlN layers. Upon thermal annealing, the ultrathin multilayer transforms into CoPt-AlN granular structure, and the thick AlN layers remain to be spacers. When the film was annealed at 400 °C, the out-of-plane direction becomes the easy axis of magnetization, although the coercivity remains small. TEM observation has proved that CoPt shows disklike shape at such an annealing temperature. When increasing the annealing temperature to 600 °C and above, the films show "isotropic" magnetic behavior due to the formation of equiaxial CoPt particles in the magnetic layers.

  15. Potential skin involvement in ALS: revisiting Charcot's observation - a review of skin abnormalities in ALS.

    PubMed

    Paré, Bastien; Gros-Louis, François

    2017-03-25

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons of the brain and spinal cord, leading to progressive paralysis and death. Interestingly, many skin changes have been reported in ALS patients, but never as yet fully explained. These observations could be due to the common embryonic origin of the skin and neural tissue known as the ectodermal germ layer. Following the first observation in ALS patients' skin by Dr Charcot in the 19th century, in the absence of bedsores unlike other bedridden patients, other morphological and molecular changes have been observed. Thus, the skin could be of interest in the study of ALS and other neurodegenerative diseases. This review summarizes skin changes reported in the literature over the years and discusses about a novel in vitro ALS tissue-engineered skin model, derived from patients, for the study of ALS.

  16. Process Capability Analysis of Vacuum Moulding for Development of Al-Al2O3 MMC

    NASA Astrophysics Data System (ADS)

    Singh, R.

    2013-01-01

    The purpose of the present study is to investigate process capability of vacuum moulding (VM) for development of Al-Al2O3 metal matrix composite (MMC). Starting from the identification of component, prototypes were prepared (with three different input parameters namely: vacuum pressure; component volume and sand grit size to give output in form of dimensional accuracy). Measurements on the coordinate measuring machine helped in calculating the dimensional tolerances of the Al-Al2O3 MMC prepared. Some important mechanical properties were also compared to verify the suitability of the components. Final components produced are acceptable as per ISO standard UNI EN 20286-I (1995). The results of study suggest that VM process lies in ±4.5 sigma (σ) limit as regard to dimensional accuracy of Al-Al2O3 MMC is concerned. This process ensures rapid production of pre-series technological prototypes and proof of concept at less production cost and time.

  17. Relative importance of hydrolyzed Al(III) species (Al(a), Al(b), and Al(c)) during coagulation with polyaluminum chloride: a case study with the typical micro-polluted source waters.

    PubMed

    Yan, Mingquan; Wang, Dongsheng; Qu, Jiuhui; He, Wenjie; Chow, Christopher W K

    2007-12-15

    The relative importance of three different Al species, Al(a) (monomeric species, instantaneous reacted species), Al(b) (medium polymer species, reacted less than 120 min), and Al(c) (colloidal or solid species, no reaction), defined by timed complexation reaction rate measured by using ferron reagent in polyaluminum chloride (PACl) was investigated in terms of DOC (dissolved organic carbon), UV(254), and turbidity removal efficiencies. Micro-polluted, typical North China, source waters were used to conduct the experiments. The results show that DOC removal is correlated well to the content of Al(b). Removal of UV(254) is determined by the content of Al(b) and Al(c), particularly Al(c). Turbidity removal is primarily related to the content of Al(c); however, Al(b) could destabilize particles efficiently, and the flocs formed by Al(b) are not as large as those formed by Al(c), which affected the settling efficiency. Unlike the preformed Al(b), the in situ formed Al(b) could remove turbidity more efficiently since Al(c) is the dominant final species formed during coagulation. Al(a) shows a strong ability to react with some unsatisfied coordinate bonds of organic matter to facilitate particle and DOC removal. The distinct coagulation feature of Al(a), Al(b), and Al(c) can be applied to develop tailor-made PACl (with the correct distribution of Al species) to match the characteristics of raw water for optimized coagulation.

  18. The lowest ionization potentials of Al2

    NASA Technical Reports Server (NTRS)

    Bauschlicher, Charles W., Jr.; Barnes, Leslie A.; Taylor, Peter R.

    1988-01-01

    Potential curves for the lowest two electronic states (X 2 sigma g + and A 2 pi u) of Al2(+) were computed using complete active space SCF/multireference CI wave functions and large Gaussian basis sets. The lowest observable vertical ionization potential (to Al2(+) X 2 sigma g +) of the Al2 X 3 pi u ground state is calculated to occur around 6.1 eV, in excellent agreement with the experimental range of 6.0 to 6.42 eV obtained in recent cluster ionization studies by Cox and co-workers. The second vertical ionization potential (to Al2(+) A 2 pi u) occurs near 6.4 eV, also within the experimental range. The adiabatic IP of 5.90 eV is in good agreement with the value of 5.8 to 6.1 eV deduced by Hanley and co-workers from the difference in thresholds between collision induced dissociation processes of Al3(+). The computed IP values are somewhat larger than those deduced from branching ratios in cluster fragmentation experiments by Jarrold and co-workers. The observation of an ionization threshold below 6.42 eV is shown to be incompatible with an Al2 ground electronic state assignment of 3 sigma g -, but the separation between the two lowest states of Al2 is so small that it is likely that both are populated in the experiments, so that this does not provide unambiguous support for the recent theoretical assignment of the ground state as 3 pi u.

  19. Influence of RCS on Al-3Mg and Al-3Mg-0.25Sc alloys

    NASA Astrophysics Data System (ADS)

    Bhovi, Prabhakar M.; Venkateswarlu, K.

    2016-02-01

    An influence of repetitive corrugation and straightening (RCS) was studied on Al-3Mg and Al-3Mg-0.25Sc alloys up to eight passes. Each pass consist of a corrugation and followed by straightening. This has resulted in introducing large plastic strain in sample, and thus led to formation of sub-micron grain sizes with high angle grain boundaries. These sub grain formation was eventually resulted in improved mechanical properties. The average grain size of Al-3Mg-0.25Sc alloy after 8 passes yielded to ∼0.6pm. Microhardness, strength properties were evaluated and it suggests that RCS was responsible for high hardness values as compared to the as cast samples. The microhardness values after RCS were 105 HV and 130 HV for Al-3Mg and Al-3Mg-0.25Sc alloys, respectively. Similarly, ∼ 40% improvement in tensile strength from 240 MPa to 370 MPa was observed for Al- 3Mg-0.25Sc alloy after RCS process.Al-3Mg and Al-3Mg-0.25Scalloys exhibited maximum strength of 220 MPa and 370 MPa, respectively. It is concluded that RCS process has a strong influence on Al- 3Mg and Al-3Mg-0.25Sc alloys for obtaining improved mechanical properties and grain refinement. In addition to RCS process and presence of AESc precipitates in Al-3Mg-0.25Sc alloy had a significant role in grain refinement and improved mechanical properties as compared to Al-3Mg alloy.

  20. Stabilization of itinerant (band) magnetism in FeAl by Ga substitution for Al

    NASA Astrophysics Data System (ADS)

    Papaconstantopoulos, D. A.; Mazin, I. I.; Hathaway, K. B.

    2001-06-01

    Band structure calculations of FeGa1-xAlx have been performed, to further investigate the stability of ferromagnetism in FeAl. The Stoner parameter increases by about 20% at the FeGa end. This is also confirmed by our spin-polarized calculations. We conclude that Ga substitution for Al is likely to stabilize the elusive (or illusive) ferromagnetic state in FeAl.

  1. Another Security Improvement over the Lin et al.'s E-voting Scheme

    NASA Astrophysics Data System (ADS)

    Asaar, Maryam Rajabzadeh; Mohajeri, Javad; Salmasizadeh, Mahmoud

    In 2003, Lin et al. have proposed an electronic voting scheme which can be utilized in large-scale elections, and claimed it detects double voting. But in this paper, by presenting an attack, we show that voters can successfully vote more than once without being detected. Hence, we propose a new modified scheme based on the Lin et al.'s scheme with the same efficiency to solve this weakness and analyze its security.

  2. Two-Phase (TiAl+TiCrAl) Coating Alloys for Titanium Aluminides

    NASA Technical Reports Server (NTRS)

    Brady, Michael P. (Inventor); Smialek, James L. (Inventor); Brindley, William J. (Inventor)

    1998-01-01

    A coating for protecting titanium aluminide alloys, including the TiAl gamma + Ti3Al (alpha(sub 2)) class, from oxidative attack and interstitial embrittlement at temperatures up to at least 1000 C. is disclosed. This protective coating consists essentially of titanium, aluminum. and chromium in the following approximate atomic ratio: Ti(41.5-34.5)Al(49-53)Cr(9.5-12.5)

  3. Small Al clusters. II - Structure and binding in Al(n) (n = 2-6, 13)

    NASA Technical Reports Server (NTRS)

    Pettersson, Lars G. M.; Bauschlicher, Charles W., Jr.; Halicioglu, Timur

    1987-01-01

    The structure and stability of aluminum clusters containing up to six atoms have been studied using correlated wave functions and extended basis sets. The lowest energy structure is planar for Al4 and Al5, but three dimensional for Al6. The icosahedral, hcp, fcc, and two planar structures of Al13 were considered at the SCF level. The lowest energy structure is the icosahedron, but the planar structures are fairly low lying even in this case. A simplified description using two- and three-body interaction potentials is found to agree well with the ab initio structures and binding energies.

  4. The Dissociation Energies of AlH2 and AlAr

    NASA Technical Reports Server (NTRS)

    Ricca, Alessandra; Partridge, Harry; Bauschlicher, Charles W., Jr.; Visscher, Luuk; Langhoff, Stephen R. (Technical Monitor)

    1995-01-01

    The D(sub 0) values for AlH2 and AlAr are computed using the coupled cluster approach in conjunction with large basis sets. Basis set superposition and spin-orbit effects are accounted for as they are sizeable due to the small binding energy. The computed dissociation energy for AlAr is 101 /cm , which is 83% of the experimental value (122.4/ cm). Our best estimate for the H2 binding energy in AlH2 is 40 +/- 28 /cm.

  5. Synthesis of core-shell AlOOH hollow nanospheres by reacting Al nanoparticles with water

    NASA Astrophysics Data System (ADS)

    Lozhkomoev, A. S.; Glazkova, E. A.; Bakina, O. V.; Lerner, M. I.; Gotman, I.; Gutmanas, E. Y.; Kazantsev, S. O.; Psakhie, S. G.

    2016-05-01

    A novel route for the synthesis of boehmite nanospheres with a hollow core and the shell composed of highly crumpled AlOOH nanosheets by oxidizing Al nanopowder in pure water under mild processing conditions is described. The stepwise events of Al transformation into boehmite are followed by monitoring the pH in the reaction medium. A mechanism of formation of hollow AlOOH nanospheres with a well-defined shape and crystallinity is proposed which includes the hydration of the Al oxide passivation layer, local corrosion of metallic Al accompanied by hydrogen evolution, the rupture of the protective layer, the dissolution of Al from the particle interior and the deposition of AlOOH nanosheets on the outer surface. In contrast to previously reported methods of boehmite nanoparticle synthesis, the proposed method is simple, and environmentally friendly and allows the generation of hydrogen gas as a by-product. Due to their high surface area and high, slit-shaped nanoporosity, the synthesized AlOOH nanostructures hold promise for the development of more effective catalysts, adsorbents, vaccines and drug carriers.

  6. Possible Involvement of Al-Induced Electrical Signals in Al Tolerance in Wheat.

    PubMed Central

    Papernik, L. A.; Kochian, L. V.

    1997-01-01

    The relationship between Al-induced depolarization of root-cell transmembrane electrical potentials (Em) and Al tolerance in wheat (Triticum aestivum L.) was investigated. Al exposure induced depolarizations of Em in the Al-tolerant wheat cultivars Atlas and ET3, but not in the Al-sensitive wheat cultivars Scout and ES3. The depolarizations of Em occured in root cap cells and as far back as 10 mm from the root tip. The depolarization was specific to Al3+; no depolarization was observed when roots were exposed to the rhizotoxic trivalent cation La3+. The Al-induced depolarization occurred in the presence of anion-channel antagonists that blocked the release of malate, indicating that the depolarization is not due to the electrogenic efflux of malate2-. K+-induced depolarizations in the root cap were of the same magnitude as Al-induced depolarizations, but did not trigger malate release, indicating that Al-induced depolarization of root cap cell membrane potentials is probably linked to, but is not sufficient to trigger, malate release. PMID:12223834

  7. High temperature deformation of NiAl and CoAl

    NASA Technical Reports Server (NTRS)

    Nix, W. D.

    1982-01-01

    The high temperature mechanical properties of the aluminides are reviewed with respect to their potential as high temperature structural materials. It is shown that NiAl and CoAl are substantially stronger than the pure metals Ni and Co at high temperatures and approach the strength of some superalloys, particularly when those superalloys are tested in "weak" directions. The factors that limit and control the high temperature strengths of NiAl and CoAl are examined to provide a basis for the development of intermetallic alloys of this type.

  8. Survey and alignment at the ALS

    SciTech Connect

    Krebs, G.F.; Lauritzen, T.; Thur, W.

    1995-11-01

    This paper describes survey and alignment at the Lawrence Berkeley National Laboratory`s Advanced Light Source (ALS) accelerators from 1993 to 1995. The ALS is a 1.0 - 1.9 GeV electron accelerator producing extremely bright synchrotron light in the UV and soft-X-ray wavelengths. At the ALS, electrons are accelerated in a LINAC to 50 MeV, injected into a booster ring for further acceleration and finally injected into the storage ring. This is shown schematically in Figure 1. The storage ring, some 200 m in circumference, has been run with electron currents above 400 mA with lifetimes as high as 24 hours. The ALS is a third generation light source and requires for efficient storage ring operation, magnets aligned to within 150 mm of their ideal position. To accomplish this a network of monuments was established and their positions measured with respect to one another. The data was reduced using GEONET`` and STAR*NET`` software. Using the monuments as reference points, magnet positions were measured and alignment confirmed using the Kem Electronic Coordinate Determination System (ECDS``). A number of other papers dealing with survey and alignment (S&A) at the ALS have been written that may further elucidate some details of the methods and systems described in this paper.

  9. 78 FR 76054 - Establishment of Class E Airspace; Chatom, AL

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-16

    ..., Georgia 30320; telephone (404) 305-6364. ] SUPPLEMENTARY INFORMATION: History On September 4, 2013, the... Above the Surface of the Earth. * * * * * ASO AL E5 Chatom, AL Roy Wilcox Airport, AL (Lat. 31 27'06''...

  10. [Al-Biruni--a universal scientist].

    PubMed

    Kujundzić, E; Masić, I

    1999-01-01

    Al-Biruni's was of Persian descent. He was born in Horesmiya and had studied mathematics, history and medicine. Acquiring knowledge from these sciences, he wrote an outstanding work on chronology of several nations and devoted it to Ziyarit ruler Kabus. He made a chronological overview of calendars from many nations, including Persians, Greeks, Egyptians, Jews, Melkitian and Nestorian Christians, Sabeyaans as well as the old Arabs. Data presented in the work, according to the later authors, were taken from very reliable sources. He was contemporary of Ibn-Sina, and thanks to their friendship, they have discussed very much miscellaneous topics. He belonged to the group of scholars, taken by Gaznevian Soultan Mahmud to a long journey to India. Afterwards Al-Biruni wrote and published detailed work "Description of India"--a work on cultural history of India. Due to excellent abilities of Al-Biruni as a philosopher and scholar, there are still significant and reliable notes about buddhistic philosophy, structure of castes and Brahmans' life style. In this Al-Biruni's masterpiece, there are many comparative analysis of Suffism and certain Indian philosophical methods. Al-Biruni's most important work is "Pharmacopoeia"--"Kitab al-saydala", which brilliantly describes all medicaments. This work has been published in many languages. He also wrote few works on astronomy and astrology. In those works he has explained some astrological events through scientific approach in a such peculiar way that nobody has ever explained before. He was also interested in sciences like geology, mineralology, geography, mathematics, psychology and many others.

  11. Al Sahawa - The Awakening: An Education and Training Resource Guide

    DTIC Science & Technology

    2015-07-01

    Mamoun Sami Rashid , Al Anbar Governor during 2005–06 described it best as a sequence of actions and events throughout Al Anbar: When we started... Rashid , Al Anbar Governor 2005 to 2006, interview with Dr. William Knarr, Colonel Dale Alford, USMC, and Lieutenant Colonel David Graves, USMC...1 . Who’s Who Appendix A Interviewees Abd al-Hakim Muhammad Rashid Muhammad al-Jughayfi, Mayor of Hadithah Abdul Qadir Mohammed Jassim Obeidi al

  12. A Comment on Eerland et al. (2016).

    PubMed

    Hart, William

    2016-03-01

    People imagine criminal behavior in greater detail and ascribe more blame to criminals when a description of a crime is written using the imperfective verb aspect (Hart & Albarracín, 2011, Experiment 3). An initiative to reproduce these findings conducted by Eerland et al. (2016) yielded a lack of replication. Eerland et al. have suggested that the original effect was likely driven by a Type I error produced by methodological aspects of the experiment, including low sample size. Recent conceptual replications of Hart and Albarracín's effect (Sherrill, Eerland, Zwaan, & Magliano, 2015), however, might imply the effect could be contingent on sample characteristics.

  13. Vibrations on Al surfaces covered by sodium

    NASA Astrophysics Data System (ADS)

    Rusina, G. G.; Eremeev, S. V.; Borisova, S. D.; Sklyadneva, I. Yu.; Chulkov, E. V.

    2006-09-01

    In this paper we present the results of a comparative study of vibrational and structural properties of the ordered (√{3}×√{3})R30∘ and c(2 × 2) phases formed by Na adatoms at room temperature on the Al(1 1 1) and Al(1 0 0) surfaces, respectively. The surface relaxation, surface phonon dispersion, and polarization of vibrational modes are calculated using the embedded-atom method. Our calculated structural parameters are in agreement with experimental and ab initio results. The obtained vibrational frequencies compare fairly well with available experimental data.

  14. Complementary and Alternative Therapies in ALS

    PubMed Central

    Bedlack, Richard S.; Joyce, Nanette; Carter, Gregory T.; Pagononi, Sabrina; Karam, Chafic

    2015-01-01

    Synopsis Given the severity of their illness and lack of effective disease modifying agents, it is not surprising that most patients with ALS consider trying complementary and alternative therapies. Some of the most commonly considered alternative therapies include special diets, nutritional supplements, cannabis, acupuncture, chelation and energy healing. This chapter reviews these in detail. We also describe 3 models by which physicians may frame discussions about alternative therapies: paternalism, autonomy and shared decision making. Finally, we review a program called ALSUntangled which using shared shared decision making to review alternative therapies for ALS. PMID:26515629

  15. The Future of Al Qa’ida

    DTIC Science & Technology

    2011-05-24

    commissions and panels; and private review and oversight bodies. C O R P O R A T I O N For More Information Visit RAND at www.rand.org Explore RAND...affiliated groups and its leadership. A range of senior officials, including Saif al-Adel and Abu Miqad al-Masri, continue to play key roles. Finally, there...20 30 40 50 60 70 2003 2005 2006 2007 2008 2009 2010 Turkey Egypt Jordan Lebanon Indonesia Pakistan Pe rc te nt ag e  of   R es po nd en ts  w it h  Co

  16. Heterogeneity of Mg Isotopes and Variable ^26Al/^27Al Ratio in FUN CAIs

    NASA Astrophysics Data System (ADS)

    Park, C.; Nagashima, K.; Hutcheon, I. D.; Wasserburg, G. J.; Papanastassiou, D. A.; Davis, A. M.; Huss, G. R.; Krot, A. N.

    2013-09-01

    We report high-precision Mg-isotope data of individual minerals from the Axtell 2271, BG82DH8, EK1-4-1, C1, TE, and CG14 FUN CAIs, which shows variations in both Mg-isotope ratio and ^26Al/^27Al ratio.

  17. Directional Solidification and Mechanical Properties of NiAl-NiAlTa Alloys

    NASA Technical Reports Server (NTRS)

    Johnson, D. R.; Chen, X. F.; Oliver, B. F.; Noebe, R. D.; Whittenberger, J. D.

    1995-01-01

    Directional solidification of eutectic alloys is a promising technique for producing in-situ composite materials exhibiting a balance of properties. Consequently, the microstructure, creep strength and fracture toughness of directionally solidified NiAl-NiAlTa alloys were investigated. Directional solidification was performed by containerless processing techniques to minimize alloy contamination. The eutectic composition was found to be NiAl-15.5 at% Ta and well-aligned microstructures were produced at this composition. A near-eutectic alloy of NiAl-14.5Ta was also investigated. Directional solidification of the near-eutectic composition resulted in microstructures consisting of NiAl dendrites surrounded by aligned eutectic regions. The off-eutectic alloy exhibited promising compressive creep strengths compared to other NiAl-based intermetallics, while preliminary testing indicated that the eutectic alloy was competitive with Ni-base single crystal superalloys. The room temperature toughness of these two-phase alloys was similar to that of polycrystalline NiAl even with the presence of the brittle Laves phase NiAlTa.

  18. Electronic circuits having NiAl and Ni.sub.3 Al substrates

    DOEpatents

    Deevi, Seetharama C.; Sikka, Vinod K.

    1999-01-01

    An electronic circuit component having improved mechanical properties and thermal conductivity comprises NiAl and/or Ni.sub.3 Al, upon which an alumina layer is formed prior to applying the conductive elements. Additional layers of copper-aluminum alloy or copper further improve mechanical strength and thermal conductivity.

  19. An Alternative Perspective on von Winterfeldt et al.'s (1997) Test of Consequence Monotonicity

    ERIC Educational Resources Information Center

    Ho, Moon-Ho R.; Regenwetter, Michel; Niederee, Reinhard; Heyer, Dieter

    2005-01-01

    D. von Winterfeldt, N.-K. Chung, R. D. Luce, and Y. Cho (see record 1997-03378-008) provided several tests for consequence monotonicity of choice or judgment, using certainty equivalents of gambles. The authors reaxiomatized consequence monotonicity in a probabilistic framework and reanalyzed von Winterfeldt et al.'s main experiment via a…

  20. Transport mechanisms of leakage current in Al2O3/InAlAs MOS capacitors

    NASA Astrophysics Data System (ADS)

    Jin, Chengji; Lu, Hongliang; Zhang, Yimen; Zhang, Yuming; Guan, He; Wu, Lifan; Lu, Bin; Liu, Chen

    2016-09-01

    An Al2O3 layer is inserted between the InAlAs layer and the metal gate in InAs/AlSb HEMTs to suppress the leakage current. The transport mechanisms of leakage current in Al2O3/InAlAs metal-oxide-semiconductor (MOS) capacitors at both positive and negative biases at different temperatures ranging from 10 °C to 70 °C are investigated. For positive bias, the leakage current is dominated by Schottky emission. Based on the fitted straight lines, the relative dielectric constant of Al2O3 and the barrier height between Al2O3 and InAlAs are extracted. However, for negative bias, the leakage current is dominated by Frenkel-Poole (F-P) emission and the depth of the trap energy level from the conduction band (ϕt) is extracted. Furthermore, authors explain the reason why the dominating mechanisms at positive and negative biases are different.

  1. The Genyornis Egg: Response to Miller et al.'s commentary on Grellet-Tinner et al., 2016

    NASA Astrophysics Data System (ADS)

    Grellet-Tinner, Gerald; Spooner, Nigel A.; Handley, Warren D.; Worthy, Trevor H.

    2017-04-01

    Williams (1981) and Williams and Rich (1991) attributed Australian Quaternary fossil eggshell that differed from that of emu Dromaius novaehollandiae to the extinct bird Genyornis newtoni without any osteological or embryonic support. Such association by proximity or abundance mirrors the case of the mistaken association of oviraptor eggs to Protoceratops in the 1920's by Andrews (Grellet-Tinner and Makovicky, 2006). No other candidate species was considered, and this attribution has been unchallenged and followed by everyone thereafter. Much research has been done on this Australian eggshell, with one result being that the extinction of the parent of this eggshell is the most well documented for a taxon in Australia (e.g., Miller et al., 1999, 2005). Grellet-Tinner et al. (2016) raised several problems with the identity of the eggshell Williams (1981) attributed to Genyornis newtoni and suggested that extinct megapodes of the genus Progura were the more likely layer of this eggshell type, therein referred to as ;putative Genyornis oological material; (PGOM). Miller et al. (2017) challenged our hypothesis stating that ;Based on the dimensions of the reconstructed Spooner Egg,Grellet-Tinner et al. (2016)argue that PGOM is too small for a bird with the body mass estimated for Genyornis (168-275 kg) … …[and] …. None of the additional PGOM observations reported byGrellet-Tinner et al. (2016)are inconsistent with a Genyornis parent;. Here we take the opportunity to respond to their critique, the basis of which resolves into a few points, which we address in turn.

  2. An impedance study of complex Al/Cu-Al2O3 electrode

    NASA Astrophysics Data System (ADS)

    Denisova, J.; Katkevics, J.; Erts, D.; Viksna, A.

    2011-06-01

    Electrochemical impedance spectroscopy (EIS) was used to investigate different Cu deposition regimes on Al surface obtained by internal electrolysis and to characterize properties of fabricated electrodes. EIS experimental data confirmed that Cu deposition by internal electrolysis is realized and the complex electrode system is obtained. The main difficulty in preparation of Al/Cu electrodes is to prevent aluminium oxidation before and during electrochemical deposition of Cu particles. In this work NaCl, CH3COONa, K2SO4, mono- and diammonium citrate electrolytes were examined to determine their suitability for impedance measurements. Al/Cu-Al2O3 electrode composition was approved by equivalent circuit analysis, optical and scanning electron microscope methods. The most optimal Cu deposition mode using internal electrolysis was determined. The obtained results are promising for future electrochemical fabrication of nanostructures directly on Al surfaces by internal electrolysis.

  3. Fundamental Influence of C on Adhesion of the Al2O3/Al Interface

    NASA Astrophysics Data System (ADS)

    Wang, Xiao-Gang; Smith, John R.; Evans, Anthony

    2002-12-01

    Our first-principles computations indicate that the clean Al2O3/Al interface is relatively weak—weaker than bulk Al. Fracture experiments reveal that the interface is relatively strong with observed failure in bulk Al, however. This paradox is resolved via doping effects of the common impurity C. We have found that only 1/3 of a monolayer of carbon segregated to the interface can increase the work of separation by a factor of 3. The resulting strong interface is consistent with fracture experiments. It arises due to void formation in the interface, which provides low-strain sites for the carbon to segregate to. The degree of void formation is consistent with the relatively high heat of oxide formation of Al.

  4. CVD Fiber Coatings for Al2O3/NiAl Composites

    NASA Technical Reports Server (NTRS)

    Boss, Daniel E.

    1995-01-01

    While sapphire-fiber-reinforced nickel aluminide (Al2O3/NiAl) composites are an attractive candidate for high-temperature structures, the significant difference in the coefficient of thermal expansion between the NiAl matrix and the sapphire fiber creates substantial residual stresses in the composite. This study seeks to produce two fiber-coating systems with the potential to reduce the residual stresses in the sapphire/NiAl composite system. Chemical vapor deposition (CVD) was used to produce both the compensating and compliant-fiber coatings for use in sapphire/NiAl composites. A special reactor was designed and built to produce the FGM and to handle the toxic nickel precursors. This process was successfully used to produce 500-foot lengths of fiber with coating thicknesses of approximately 3 microns, 5 microns, and 10 microns.

  5. Temperature dependence of the activity of Al in dilute Ni(Al) solid solutions

    SciTech Connect

    Jiang Yong; Smith, J. R.; Evans, A. G.

    2006-12-01

    Activities of dilute Al solid solutions in Ni are determined from a first-principles approach. Both thermal lattice vibration and electronic contributions to free energies are considered and compared. Vibrational contributions tend to dominate the temperature dependencies of the free energies, though electron thermal effects are significant. Calculations show opposing temperature trends for the formation enthalpies and entropies, leading to a partial cancellation of their role in the overall energetics. Nevertheless, their remaining temperature effects are strong. Over the temperature range, 400 KAl activity coefficient varies by 15 orders of magnitude, due to the relative strength of Al-Ni and Al-Al bonds. The Ni activity coefficient only varies less than 4% over the same range. Calculational results compare well with available experimental data. The thermodynamic principles elucidated from the calculations are used to provide a fundamental interpretation.

  6. Al/sub 2/O/sub 3/ adherence on CoCrAl alloys

    SciTech Connect

    Kingsley, L.M.

    1980-04-01

    Adherence of protective oxides on NiCrAl and CoCrAl superalloys has been promoted by a dispersion of a highly oxygen reactive element or its oxide being produced within the protection system. Two aspects of this subject are investigated here: the use of Al/sub 2/O/sub 3/ as both the dispersion and protective oxide; and the production of an HfO/sub 2/ dispersion while simultaneously aluminizing the alloy. It was found that an Al/sub 2/O/sub 3/ dispersion will act to promote the adherence of an external scale of Al/sub 2/O/sub 3/ to a degree comparable to previously tested dispersions and an HfO/sub 2/ dispersion comparable to that produced by a Rhines pack treatment is produced during aluminization.

  7. 1300 K compressive properties of a reaction milled NiAl-AlN composites

    NASA Technical Reports Server (NTRS)

    Whittenberger, J. Daniel; Arzt, Eduard; Luton, Michael J.

    1990-01-01

    When B2 crystal-structure nickel aluminide is subjected to high-intensity mechanical ball milling in a liquid nitrogen bath, or 'cryomilling', an NiAl composite is obtained which contains about 10 vol pct AlN particles. This composition arises from the incorporation of N during cryomilling; during subsequent thermomechanical processing, the N reacts with Al. While compressive testing of extruded or isostatically pressed specimens at 1300 K indicated that strength at relatively fast strain rates is slightly dependent on consolidation method, slower strain rates indicate no clear dependency on densification technique: four different consolidation methods were found to yield similar creep strengths. The creep properties of NiAl-AlN are similar to those of the single-crystal Ni-base superalloy NASAIR 100.

  8. Bonding characters of Al-containing bulk metallic glasses studied by 27Al NMR.

    PubMed

    Xi, X K; Sandor, M T; Wang, H J; Wang, J Q; Wang, W H; Wu, Y

    2011-03-23

    We report very small (27)Al metallic shifts in a series of Cu-Zr-Al bulk metallic glasses. This observation and the Korringa type of spin-lattice relaxation behavior suggest that s-character wavefunctions weakly participate in bonding and opens the possibility of enhanced covalency (pd hybridization) with increasing Al concentration, in good agreement with elastic constants and hardness measurements. Moreover, ab initio calculations show that this bonding character originates from the strong Al 3p band and Zr 4d band hybridization since their atomic energy levels are closer to each other while the Al 3s band is localized far below the Fermi level. This study might provide a chemical view for understanding flow and fracture mechanisms of these bulk glass-forming alloys.

  9. Epidemiology and neurological complications of infection by the Zika virus: a new emerging neurotropic virus.

    PubMed

    Carod-Artal, Francisco J

    2016-04-01

    Introduccion. El actual brote epidemico por virus Zika se inicio en 2015 y en la actualidad afecta a 31 paises y territorios en America. Se revisan los aspectos epidemiologicos y clinicos asociados con la infeccion por virus Zika. Desarrollo. Desde 2007, 55 paises de America, Asia, Africa y Oceania han detectado transmision local del virus. La actual epidemia ha afectado a casi 1,5 millones de personas en Brasil. El 80% de los casos son asintomaticos. La enfermedad por virus Zika cursa con fiebre, exantema maculopapular, artralgias y conjuntivitis no purulenta. Los sintomas suelen ser autolimitados y duran una semana. Se ha descrito un aumento de la incidencia de los casos de microcefalia, lesiones retinianas y sindrome de Guillain-Barre asociados con el virus Zika. El sindrome de Guillain-Barre asociado al Zika en la Polinesia es una variante axonal motora pura. El ARN del virus Zika se ha identificado en muestras de tejido cerebral, placenta y liquido amniotico de niños con microcefalia y en perdidas fetales de mujeres infectadas por Zika durante el embarazo. Se recomienda realizar la prueba de reaccion en cadena de la polimerasa mediante transcriptasa inversa para detectar ARN virico y pruebas serologicas (IgM ELISA y anticuerpos neutralizantes) para confirmar una infeccion por Zika. El diagnostico diferencial incluye la infeccion por virus dengue y chikungunya. Conclusiones. Existe un conocimiento limitado sobre los mecanismos patogenicos implicados y las consecuencias a largo plazo de la infeccion por virus Zika en adultos y recien nacidos.

  10. Formation of gamma(sup prime)-Ni3Al via the Peritectoid Reaction: gamma + beta (+ Al2O3)=gamma(sup prime)(+ Al2O3)

    NASA Technical Reports Server (NTRS)

    Copeland, Evan

    2008-01-01

    The activities of Al and Ni were measured using multi-cell Knudsen effusion-cell mass spectrometry (multi-cell KEMS), over the composition range 8-32 at.%Al and temperature range T=1400-1750 K in the Ni-Al-O system. These measurements establish that equilibrium solidification of gamma(sup prime)-Ni3Al-containing alloys occurs by the eutectic reaction, L (+ Al2O3)=gamma + Beta(+ Al2O3), at 1640 +/- 1 K and a liquid composition of 24.8 +/- 0.2 at.%al (at an unknown oxygen content). The {gamma + Beta (+Al2O3} phase field is stable over the temperature range 1633-1640 K, and gamma(sup prime)-Ni3Al forms via the peritectoid, gamma + Beta (+ Al2O3)=gamma(sup prime) (+ Al2O3), at 1633 +/- 1 K. This behavior is consistent with the current Ni-Al phase diagram and a new diagram is proposed. This new Ni-Al phase diagram explains a number of unusual steady-state solidification structures reported previously and provides a much simpler reaction scheme in the vicinity of the gamma(sup prime)-Ni2Al phase field.

  11. Formation of gamma'-Ni3Al via the Peritectoid Reaction: gamma plus beta (+Al2O3) equals gamma'(+Al2O3)

    NASA Technical Reports Server (NTRS)

    Copland, Evan

    2008-01-01

    The activities of Al and Ni were measured using multi-cell Knudsen effusion-cell mass spectrometry (multi-cell KEMS), over the composition range 8 - 32 at.%Al and temperature range T = 1400 - 1750 K in the Ni-Al-O system. These measurements establish that equilibrium solidification of gamma'-Ni3Al-containing alloys occurs by the eutectic reaction, L (+ Al2O3) = gamma + beta (+ Al2O3), at 1640 plus or minus 1 K and a liquid composition of 24.8 plus or minus 0.2 at.%Al (at an unknown oxygen content). The {gamma + beta + Al2O3} phase field is stable over the temperature range 1633 - 1640 K, and gamma'-Ni3Al forms via the peritectiod, gamma + beta (+ Al2O3) = gamma'(+ Al2O3), at 1633 plus or minus 1 K. This behavior is inconsistent with the current Ni-Al phase diagram and a new diagram is proposed. This new Ni-Al phase diagram explains a number of unusual steady state solidification structures reported previously and provides a much simpler reaction scheme in the vicinity of the gamma'-Ni3Al phase field.

  12. 76 FR 62481 - Incapital LLC, et al.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-07

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Incapital LLC, et al.; Notice of Application September 30, 2011. AGENCY: Securities and Exchange Commission (``Commission''). ACTION: Notice of application for an order under section 12(d)(1)(J) of...

  13. Electron impact exctation of Al X

    NASA Astrophysics Data System (ADS)

    Aggarwal, Kanti; Keenan, Francis

    2013-05-01

    Emission lines of Al ions, including Al X, are important for the modeling and diagnostics of lasing, fusion and astrophysical plasmas, for which atomic data are required for a variety of parameters, such as energy levels, radiative rates (A- values), and excitation rates or equivalently the effective collision strengths (Υ), which are obtained from the electron impact collision strengths (Ω). Experimentally, energy levels are available for Al X on the NIST website, but there is paucity for accurate collisional atomic data. Therefore, here we report a complete set of results (namely energy levels, radiative rates, and effective collision strengths) for all transitions among the lowest 98 levels of Al X. These levels belong to the (1s2) 2s2, 2s2p, 2p2, 2s3 l, 2p3 l, 2s4 l, and 2p4 l configurations. Finally, we also report the A- values for four types of transitions, namely electric dipole (E1), electric quadrupole (E2), magnetic dipole (M1), and magnetic quadrupole (M2), because these are also required for plasma modeling. For our calculations of wavefunctions, we have adopted the fully relativistic GRASP code, and for the calculations of Ω, the Dirac atomic R-matrix code (DARC) of PH Norrington and IP Grant. Additionally, parallel ca

  14. Kinematics of Disease Progression in Bulbar ALS

    ERIC Educational Resources Information Center

    Yunusova, Yana; Green, Jordan R.; Lindstrom, Mary J.; Ball, Laura J.; Pattee, Gary L.; Zinman, Lorne

    2010-01-01

    The goal of this study was to investigate the deterioration of lip and jaw movements during speech longitudinally in three individuals diagnosed with bulbar amyotrophic lateral sclerosis (ALS). The study was motivated by the need to understand the relationship between physiologic changes in speech movements and clinical measures of speech…

  15. U-ALS: A Ubiquitous Learning Environment

    ERIC Educational Resources Information Center

    Piovesan, Sandra Dutra; Passerino, Liliana Maria; Medina, Roseclea Duarte

    2012-01-01

    The diffusion of the use of the learning virtual environments presents a great potential for the development of an application which meet the necessities in the education area. In view of the importance of a more dynamic application and that can adapt itself continuously to the students' necessities, the "U-ALS" (Ubiquitous Adapted Learning…

  16. 75 FR 1420 - Alabama Disaster # AL-00025

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-11

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION Alabama Disaster AL-00025 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a notice of an Administrative declaration of a disaster for the State of Alabama dated...

  17. 78 FR 4967 - Alabama Disaster #AL-00046

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-23

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION Alabama Disaster AL-00046 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a notice of an Administrative declaration of a disaster for the State of ALABAMA dated...

  18. 76 FR 29810 - Alabama Disaster #AL-00037

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-23

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION Alabama Disaster AL-00037 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a Notice of the Presidential declaration of a major disaster for Public Assistance Only for...

  19. 75 FR 474 - Alabama Disaster #AL-00026

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-05

    ... [Federal Register Volume 75, Number 2 (Tuesday, January 5, 2010)] [Notices] [Pages 474-475] [FR Doc No: E9-31259] SMALL BUSINESS ADMINISTRATION [Disaster Declaration 11988 and 11989] Alabama Disaster AL-00026 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a Notice...

  20. 78 FR 26100 - Alabama Disaster #AL-00050

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-03

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION Alabama Disaster AL-00050 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a notice of an Administrative declaration of a disaster for the State of Alabama dated...