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Sample records for aggregated immunoglobulin e-receptor

  1. Intravenous immunoglobulins induce CD32-mediated platelet aggregation in vitro.

    PubMed

    Pollreisz, A; Assinger, A; Hacker, S; Hoetzenecker, K; Schmid, W; Lang, G; Wolfsberger, M; Steinlechner, B; Bielek, E; Lalla, E; Klepetko, W; Volf, I; Ankersmit, H J

    2008-09-01

    Intravenous immunoglobulins (IVIg) and cytomegalovirus immunoglobulins (CMVIg) are currently finding increased acceptance in clinical states of high immune activity and in transplant recipients. A rare side-effect of their application is intravascular thrombosis, which is thought to be related to pre-existing hyperviscosity. In a previous study we have shown that rabbit antithymocyte globulin causes platelet aggregation in vitro via the Fc IgG receptor (CD32). To investigate if IVIg and CMVIg have the potential to cause CD32-dependent platelet aggregation. The influence of CMVIg or IVIg on platelets pre-incubated with or without monoclonal antibody AT10 was studied in an aggregometer. Expression of platelet surface activation marker CD62P was determined by fluorescence-activated cell sorting analysis and presence of soluble CD40L (sCD40L) was evaluated by enzyme-linked immunosorbent assay. All in vitro experiments were performed using platelet concentrates from the blood bank, at therapeutic concentrations of immunoglobulins. Results Incubation of platelets with CMVIg and IVIg markedly induced platelet aggregation, and increased expression of CD62P and secretion of sCD40L. The capacity of CMVIg and IVIg to induce platelet aggregation was completely abrogated by adding the blocking antibody AT10 directed against the low-affinity Fc IgG receptor (CD32). Our results suggest that CMVIg and IVIg solutions with activating Fc domains are able to bind CD32 on platelets and cause platelet aggregation in vitro. These results indicate a mechanism by which in vivo intravascular thrombosis may be explained and suggest caution with concomitant use of packed platelets and IVIg in autoimmune diseases in the clinical setting.

  2. Ethanol Inhibits High-Affinity Immunoglobulin E Receptor (FcεRI) Signaling in Mast Cells by Suppressing the Function of FcεRI-Cholesterol Signalosome

    PubMed Central

    Draberova, Lubica; Paulenda, Tomas; Halova, Ivana; Potuckova, Lucie; Bugajev, Viktor; Bambouskova, Monika; Tumova, Magda; Draber, Petr

    2015-01-01

    Ethanol has multiple effects on biochemical events in a variety of cell types, including the high-affinity immunoglobulin E receptor (FcεRI) signaling in antigen-activated mast cells. However, the underlying molecular mechanism remains unknown. To get better understanding of the effect of ethanol on FcεRI-mediated signaling we examined the effect of short-term treatment with non-toxic concentrations of ethanol on FcεRI signaling events in mouse bone marrow-derived mast cells. We found that 15 min exposure to ethanol inhibited antigen-induced degranulation, calcium mobilization, expression of proinflammatory cytokine genes (tumor necrosis factor-α, interleukin-6, and interleukin-13), and formation of reactive oxygen species in a dose-dependent manner. Removal of cellular cholesterol with methyl-β-cyclodextrin had a similar effect and potentiated some of the inhibitory effects of ethanol. In contrast, exposure of the cells to cholesterol-saturated methyl-β-cyclodextrin abolished in part the inhibitory effect of ethanol on calcium response and production of reactive oxygen species, supporting lipid-centric theories of ethanol action on the earliest stages of mast cell signaling. Further studies showed that exposure to ethanol and/or removal of cholesterol inhibited early FcεRI activation events, including tyrosine phosphorylation of the FcεRI β and γ subunits, SYK kinases, LAT adaptor protein, phospholipase Cγ, STAT5, and AKT and internalization of aggregated FcεRI. Interestingly, ethanol alone, and particularly in combination with methyl-β-cyclodextrin, enhanced phosphorylation of negative regulatory tyrosine 507 of LYN kinase. Finally, we found that ethanol reduced passive cutaneous anaphylactic reaction in mice, suggesting that ethanol also inhibits FcεRI signaling under in vivo conditions. The combined data indicate that ethanol interferes with early antigen-induced signaling events in mast cells by suppressing the function of Fc

  3. Ethanol Inhibits High-Affinity Immunoglobulin E Receptor (FcεRI) Signaling in Mast Cells by Suppressing the Function of FcεRI-Cholesterol Signalosome.

    PubMed

    Draberova, Lubica; Paulenda, Tomas; Halova, Ivana; Potuckova, Lucie; Bugajev, Viktor; Bambouskova, Monika; Tumova, Magda; Draber, Petr

    2015-01-01

    Ethanol has multiple effects on biochemical events in a variety of cell types, including the high-affinity immunoglobulin E receptor (FcεRI) signaling in antigen-activated mast cells. However, the underlying molecular mechanism remains unknown. To get better understanding of the effect of ethanol on FcεRI-mediated signaling we examined the effect of short-term treatment with non-toxic concentrations of ethanol on FcεRI signaling events in mouse bone marrow-derived mast cells. We found that 15 min exposure to ethanol inhibited antigen-induced degranulation, calcium mobilization, expression of proinflammatory cytokine genes (tumor necrosis factor-α, interleukin-6, and interleukin-13), and formation of reactive oxygen species in a dose-dependent manner. Removal of cellular cholesterol with methyl-β-cyclodextrin had a similar effect and potentiated some of the inhibitory effects of ethanol. In contrast, exposure of the cells to cholesterol-saturated methyl-β-cyclodextrin abolished in part the inhibitory effect of ethanol on calcium response and production of reactive oxygen species, supporting lipid-centric theories of ethanol action on the earliest stages of mast cell signaling. Further studies showed that exposure to ethanol and/or removal of cholesterol inhibited early FcεRI activation events, including tyrosine phosphorylation of the FcεRI β and γ subunits, SYK kinases, LAT adaptor protein, phospholipase Cγ, STAT5, and AKT and internalization of aggregated FcεRI. Interestingly, ethanol alone, and particularly in combination with methyl-β-cyclodextrin, enhanced phosphorylation of negative regulatory tyrosine 507 of LYN kinase. Finally, we found that ethanol reduced passive cutaneous anaphylactic reaction in mice, suggesting that ethanol also inhibits FcεRI signaling under in vivo conditions. The combined data indicate that ethanol interferes with early antigen-induced signaling events in mast cells by suppressing the function of Fc

  4. Effects of tau domain-specific antibodies and intravenous immunoglobulin on tau aggregation and aggregate degradation.

    PubMed

    Esteves-Villanueva, Jose O; Trzeciakiewicz, Hanna; Loeffler, David A; Martić, Sanela

    2015-01-20

    Tau pathology, including neurofibrillary tangles, develops in Alzheimer's disease (AD). The aggregation and hyperphosphorylation of tau are potential therapeutic targets for AD. Administration of anti-tau antibodies reduces tau pathology in transgenic "tauopathy" mice; however, the optimal tau epitopes and conformations to target are unclear. Also unknown is whether intravenous immunoglobulin (IVIG) products, currently being evaluated in AD trials, exert effects on pathological tau. This study examined the effects of anti-tau antibodies targeting different tau epitopes and the IVIG Gammagard on tau aggregation and preformed tau aggregates. Tau aggregation was assessed by transmission electron microscopy and fluorescence spectroscopy, and the binding affinity of the anti-tau antibodies for tau was evaluated by enzyme-linked immunosorbent assays. Antibodies used were anti-tau 1-150 ("D-8"), anti-tau 259-266 ("Paired-262"), anti-tau 341-360 ("A-10"), and anti-tau 404-441 ("Tau-46"), which bind to tau's N-terminus, microtubule binding domain (MBD) repeat sequences R1 and R4, and the C-terminus, respectively. The antibodies Paired-262 and A-10, but not D-8 and Tau-46, reduced tau fibrillization and degraded preformed tau aggregates, whereas the IVIG reduced tau aggregation but did not alter preformed aggregates. The binding affinities of the antibodies for the epitope for which they were specific did not appear to be related to their effects on tau aggregation. These results confirm that antibody binding to tau's MBD repeat sequences may inhibit tau aggregation and indicate that such antibodies may also degrade preformed tau aggregates. In the presence of anti-tau antibodies, the resulting tau morphologies were antigen-dependent. The results also suggested the possibility of different pathways regulating antibody-mediated inhibition of tau aggregation and antibody-mediated degradation of preformed tau aggregates.

  5. Distribution and Dynamics of Rat Basophilic Leukemia Immunoglobulin E Receptors (FcɛRI) on Planar Ligand-Presenting Surfaces

    PubMed Central

    Spendier, Kathrin; Carroll-Portillo, Amanda; Lidke, Keith A.; Wilson, Bridget S.; Timlin, Jerilyn A.; Thomas, James L.

    2010-01-01

    Abstract There is considerable interest in the signaling mechanisms of immunoreceptors, especially when triggered with membrane-bound ligands. We have quantified the spatiotemporal dynamics of the redistribution of immunoglobulin E-loaded receptors (IgE-FcɛRI) on rat basophilic leukemia-2H3 mast cells in contact with fluid and gel-phase membranes displaying ligands for immunoglobulin E, using total internal reflection fluorescence microscopy. To clearly separate the kinetics of receptor redistribution from cell spreading, and to precisely define the initial contact time (±50 ms), micropipette cell manipulation was used to bring individual cells into contact with surfaces. On ligand-free surfaces, there are micron-scale heterogeneities in fluorescence that likely reflect regions of the cell that are more closely apposed to the substrate. When ligands are present, receptor clusters form with this same size scale. The initial rate of accumulation of receptors into the clusters is consistent with diffusion-limited trapping with D ∼10−1μm2/s. These results support the hypothesis that clusters form by diffusion to cell-surface contact regions. Over longer timescales (>10 s), individual clusters moved with both diffusive and directed motion components. The dynamics of the cluster motion is similar to the dynamics of membrane fluctuations of cells on ligand-free fluid membranes. Thus, the same cellular machinery may be responsible for both processes. PMID:20643056

  6. Isoflavones suppress the expression of the FcεRI high-affinity immunoglobulin E receptor independent of the estrogen receptor.

    PubMed

    Yamashita, Shuya; Tsukamoto, Shuntaro; Kumazoe, Motofumi; Kim, Yoon-hee; Yamada, Koji; Tachibana, Hirofumi

    2012-08-29

    Isoflavones found in soybeans and soy products possess clinically relevant properties. However, the anti-allergic effect of isoflavones has been poorly studied. We examined the effects of isoflavones, genistein, daidzein, and equol, on the expression of the high-affinity immunoglobulin E (IgE) receptor, FcεRI, which plays a central role in IgE-mediated allergic response. Flow cytometric analysis showed that all of these isoflavones reduced the cell surface expression of FcεRI on mouse bone-marrow-derived mast cells and human basophilic KU812 cells. All isoflavones decreased the levels of the FcεRIα mRNA in the cells. Genistein reduced the mRNA expression of the β chain, and daidzein and equol downregulated that of the γ chain. The suppressive effects of isoflavones on FcεRI expression were unaffected by ICI 182,780, an estrogen receptor antagonist, suggesting that these effects were independent of estrogen receptors.

  7. Inhibitory Effect of Carotenoids on the Degranulation of Mast Cells via Suppression of Antigen-induced Aggregation of High Affinity IgE Receptors*

    PubMed Central

    Sakai, Shota; Sugawara, Tatsuya; Matsubara, Kiminori; Hirata, Takashi

    2009-01-01

    Carotenoids have been demonstrated to possess antioxidative and anti-inflammatory effects. However, there is no report that the effects of carotenoids on degranulation of mast cell is critical for type I allergy. In this study, we focused on the effect of carotenoids on antigen-induced degranulation of mast cells. Fucoxanthin, astaxanthin, zeaxanthin, and β-carotene significantly inhibited the antigen-induced release of β-hexosaminidase in rat basophilic leukemia 2H3 cells and mouse bone marrow-derived mast cells. Those carotenoids also inhibited antigen-induced aggregation of the high affinity IgE receptor (FcϵRI), which is the most upstream of the degranulating signals of mast cells. Furthermore, carotenoids inhibited FcϵRI-mediated intracellular signaling, such as phosphorylation of Lyn kinase and Fyn kinase. It suggests that the inhibitory effect of carotenoids on the degranulation of mast cells were mainly due to suppressing the aggregation of FcϵRI followed by intracellular signaling. In addition, those carotenoids inhibited antigen-induced translocation of FcϵRI to lipid rafts, which are known as platforms of the aggregation of FcϵRI. We assume that carotenoids may modulate the function of lipid rafts and inhibit the translocation of FcϵRI to lipid rafts. This is the first report that focused on the aggregation of FcϵRI to investigate the mechanism of the inhibitory effects on the degranulation of mast cells and evaluated the functional activity of carotenoids associated with lipid rafts. PMID:19700409

  8. Thermal aggregation of human immunoglobulin G in arginine solutions: Contrasting effects of stabilizers and destabilizers.

    PubMed

    Yoshizawa, Shunsuke; Arakawa, Tsutomu; Shiraki, Kentaro

    2017-11-01

    Arginine is widely used as aggregation suppressor of proteins in biotechnology and pharmaceutics. However, why the effect of arginine depends on the types of proteins and stresses, including monoclonal antibodies, is still unclear. Here we investigated the precise processes of the thermal aggregation of human immunoglobulin G (IgG) in the presence of additives. As expected, arginine was the best additive to suppress the formation of insoluble aggregates during heat treatment, though it was unable to preserve the monomer content. A systematic analysis of the additives showed that sugars and kosmotropic ion inhibit the formation of soluble oligomers. These behaviors indicate that the thermal aggregation of IgG occurs by (i) the formation of soluble oligomers, which is triggered by the unfolding process that can be stabilized by typical osmolytes, and (ii) the formation of insoluble aggregates through weak cluster-cluster interactions, which can be suppressed by arginine. Understanding the detailed mechanism of arginine will provide useful information for the rational formulation design of antibodies. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Diminished clearance of soluble aggregates of human immunoglobulin G in patients with rheumatoid arthritis.

    PubMed

    Lobatto, S; Daha, M R; Westedt, M L; Pauwels, E K; Evers-Schouten, J H; Voetman, A A; Cats, A; van Es, L A

    1989-01-01

    Investigation of the capacity of the mononuclear phagocyte system to remove immune complexes from the circulation was performed by the administration of 125I-labelled aggregates of human immunoglobulin G (AIgG) to patients with seropositive rheumatoid arthritis and healthy volunteers. It was found that the rate at which AIgG disappeared from the circulation was significantly prolonged in patients with RA, t1/2 61 +/- 49 min, versus 26 +/- 8 min in healthy volunteers (p less than 0.01). We were not able to establish a correlation between the t1/2 of AIgG and immune complex levels in the circulation, or between t1/2 and articular disease activity (Ritchie index). The sites of removal of AIgG from the circulation were analysed by determining radioactivity levels detectable over liver, spleen and heart. No correlation was found between t1/2 and liver/spleen uptake ratios. We have demonstrated that the removal of AIgG from the circulation of patients with RA is abnormal, though the biological significance of this finding remains to be determined.

  10. Effect of Excipients on Liquid-Liquid Phase Separation and Aggregation in Dual Variable Domain Immunoglobulin Protein Solutions.

    PubMed

    Raut, Ashlesha S; Kalonia, Devendra S

    2016-03-07

    Liquid-liquid phase separation (LLPS) and aggregation can reduce the physical stability of therapeutic protein formulations. On undergoing LLPS, the protein-rich phase can promote aggregation during storage due to high concentration of the protein. Effect of different excipients on aggregation in protein solution is well documented; however data on the effect of excipients on LLPS is scarce in the literature. In this study, the effect of four excipients (PEG 400, Tween 80, sucrose, and hydroxypropyl beta-cyclodextrin (HPβCD)) on liquid-liquid phase separation and aggregation in a dual variable domain immunoglobulin protein solution was investigated. Sucrose suppressed both LLPS and aggregation, Tween 80 had no effect on either, and PEG 400 increased LLPS and aggregation. Attractive protein-protein interactions and liquid-liquid phase separation decreased with increasing concentration of HPβCD, indicating its specific binding to the protein. However, HPβCD had no effect on the formation of soluble aggregates and fragments in this study. LLPS and aggregation are highly temperature dependent; at low temperature protein exhibits LLPS, at high temperature protein exhibits aggregation, and at an intermediate temperature both phenomena occur simultaneously depending on the solution conditions.

  11. Pseudocatalytic Antiaggregation Activity of Antibodies: Immunoglobulins can Influence α-Synuclein Aggregation at Substoichiometric Concentrations.

    PubMed

    Breydo, Leonid; Morgan, Dave; Uversky, Vladimir N

    2016-04-01

    Protein aggregation is involved in a variety of diseases. Alteration of the aggregation pathway, either to produce less toxic structures or to increase aggregate clearance, is a promising therapeutic route. Both active and passive immunization has been used for this purpose. However, the mechanism of action of antibodies on protein aggregates is not completely clear especially given poor ability of antibodies to cross blood-brain barrier. Here, we have shown that antibodies can interfere with protein aggregation at substoichiometric concentrations (as low as 1:1000 antibody to protein ratio). This is an indication that antibodies interact with aggregation intermediates in chaperone-like manner altering the aggregation pathways at very low antibody levels. This observation supports earlier suggestions that antibodies can inhibit aggregation by interaction with low abundance aggregation intermediates.

  12. Macrophage triggering by aggregated immunoglobulins. II. Comparison of IgE and IgG aggregates or immune complexes.

    PubMed Central

    Pestel, J; Dessaint, J P; Joseph, M; Bazin, H; Capron, A

    1984-01-01

    Macrophages incubated with complexed or aggregated IgE released beta-glucuronidase (beta-G) within 30 min. In contrast in the presence of aggregated or complexed IgG, macrophages liberated equivalent amount of beta-G only after 6 h incubation. In addition the rapid macrophage stimulation induced by aggregated IgE was also followed by a faster 3H-glucosamine incorporation when compared to the delayed activation caused by aggregated IgG. However, macrophages stimulated either by IgG or by IgE oligomers produced the same percentage of plasminogen activator at 24 h. In contrast, while the interaction between macrophages and aggregated IgE was only followed by a peak of cyclic GMP and a beta-G release during the first 30 min of incubation, the interaction between macrophages and IgG oligomers was accompanied by a simultaneous increase of cyclic GMP and AMP nucleotides and by an absence of beta-G exocytosis. Moreover, the beta-G release induced by aggregated IgE was increased when macrophages were preincubated with aggregated IgG. This additive effect was not observed in the reverse situation. Finally macrophages activated by IgG oligomers were demonstrated to exert a cytotoxic effect on tumour cells and to kill schistosomula in the presence of a low level of complement. Taken together these results underline the peculiar ability of aggregated or complexed IgE to trigger rapidly the macrophage activation compared to aggregated IgG and can explain the important role of complexed IgE in some macrophage dependent cytotoxicity mechanisms (i.e. in parasitic diseases). PMID:6088135

  13. Elimination of soluble 123I-labelled aggregates of human immunoglobulin G in humans; the effect of splenectomy.

    PubMed

    Halma, C; Daha, M R; van Furth, R; Camps, J A; Evers-Schouten, J H; Pauwels, E K; Lobatto, S; Van Es, L A

    1989-07-01

    To study the role of the spleen in the elimination of immune complexes we examined mononuclear phagocyte system function in eight healthy controls and eight splenectomized patients, with soluble 123I-labelled aggregates of human immunoglobulin G (AIgG). No differences were found between the two groups in elimination and degradation of AIgG. The loss of splenic function was compensated for by increased uptake of AIgG by the liver. With the dose of 123I-AIgG used in this study (10 micrograms/kg body weight), significant generation of C3a was observed. No correlation was found between erythrocyte CR1 number and the fraction of aggregates that bound to erythrocytes.

  14. Epigallocatechin-3-gallate preferentially induces aggregation of amyloidogenic immunoglobulin light chains

    PubMed Central

    Hora, Manuel; Carballo-Pacheco, Martin; Weber, Benedikt; Morris, Vanessa K.; Wittkopf, Antje; Buchner, Johannes; Strodel, Birgit; Reif, Bernd

    2017-01-01

    Antibody light chain amyloidosis is a rare disease caused by fibril formation of secreted immunoglobulin light chains (LCs). The huge variety of antibody sequences puts a serious challenge to drug discovery. The green tea polyphenol epigallocatechin-3-gallate (EGCG) is known to interfere with fibril formation in general. Here we present solution- and solid-state NMR studies as well as MD simulations to characterise the interaction of EGCG with LC variable domains. We identified two distinct EGCG binding sites, both of which include a proline as an important recognition element. The binding sites were confirmed by site-directed mutagenesis and solid-state NMR analysis. The EGCG-induced protein complexes are unstructured. We propose a general mechanistic model for EGCG binding to a conserved site in LCs. We find that EGCG reacts selectively with amyloidogenic mutants. This makes this compound a promising lead structure, that can handle the immense sequence variability of antibody LCs. PMID:28128355

  15. Structural Characterization of the Partially Folded Intermediates of An Immunoglobulin Light Chain Leading to Amyloid Fibrillation And Amorphous Aggregation

    SciTech Connect

    Qin, Z.; Hu, D.; Zhu, M.; Fink, A.L.; /UC, Santa Cruz

    2007-07-12

    Immunoglobulin light chain deposition diseases involve various types of extracellular deposition of light chain variable domains, including amyloid fibrils and amorphous deposits. The decreased thermodynamic stability of the light chain is believed to be the major factor leading to fibrillation. However, the differences in the nature of the deposits among the light chain deposition diseases raise the question of whether the mechanisms leading to fibrillar or amorphous aggregation is different. In this study, we generated two partially folded intermediates of the light chain variable domain SMA in the presence of guanidine hydrochloride (GuHCl) and characterized their conformations. The more unfolded intermediate formed fibrils most rapidly, while the more native-like intermediate predominantly led to amorphous deposits. The results also show that the monomeric, rather than the dimeric state, was critical for fibrillation. The data also indicate that fibril elongation involves addition of a partially unfolded intermediate, rather than the native state. We postulate that a more highly unfolded intermediate is more suited to undergo the topological rearrangements necessary to form amyloid fibrils than a more structured one and that this also correlates with increased destabilization. In the case of light chain aggregation, it appears that more native-like intermediate conformations are more prone to form amorphous deposits.

  16. Clearance of soluble aggregates of human immunoglobulin G in healthy volunteers and chimpanzees.

    PubMed

    Lobatto, S; Daha, M R; Voetman, A A; Evers-Schouten, J H; Van Es, A A; Pauwels, E K; Van Es, L A

    1987-07-01

    Using aggregates of IgG (AIgG) obtained by heat aggregation of a 16 g% human IgG solution, we sought a method for measuring the function of the mononuclear phagocyte system with a probe that bears more resemblance to soluble immune complexes than erythrocytes coated with anti-rhesus IgG (EIgG). It was found that intravenous administration of 10 micrograms AIgG/kg body weight did not cause any detectable side effects in chimpanzees. In nine healthy volunteers, a dose of 10 micrograms AIgG/kg body weight was used without any adverse reactions. AIgG is cleared from the human circulation with a t1/2 of 26 +/- 8 min (mean +/- SD). The site of clearance is predominantly the liver, as shown by an average liver spleen uptake ratio of 230:100. In whole blood obtained from the volunteers, it was found that erythrocytes bound significant amounts of AIgG, suggesting that CR1 on erythrocytes is involved in the clearance of complement activating immune complexes in humans. In five of the volunteers, clearance studies with EIgG had been done in a previous study. EIgG was cleared from the circulation with a t1/2 of 30 +/- 6.2 min (mean +/- SD). The predominant site of clearance of EIgG was the spleen. These data indicate that sensitized red blood cells are cleared from the circulation differently from soluble IgG aggregates.

  17. Quantitative relationships between aggregation of IgE receptors, generation of intracellular signals, and histamine secretion in rat basophilic leukemia (2H3) cells. Enhanced responses with heavy water

    SciTech Connect

    Maeyama, K.; Hohman, R.J.; Metzger, H.; Beaven, M.A.

    1986-02-25

    RBL-2H3 cells (a tumor analog of rat mast cells) have plasma-membrane receptors that bind immunoglobulin E, which when aggregated, initiate degranulation. As in other systems, secretion is preceeded by enhanced hydrolysis of inositol phospholipids and by a rise in intracellular Ca2+. Unlike the responses of many other cells, however, both of these earlier events require extracellular Ca2+. The relationship of these events to each other and to the subsequent secretory process is thus unclear. By exposing cells to covalent oligomers of IgE one can demonstrate substantial increases in secretion of histamine by increasing the concentration and size of the oligomers or by using heavy water (D2O) in the medium. We have used such maneuvers to examine the quantitative relationships between aggregation of the receptors and the breakdown of inositol phospholipids, the increase in cytosolic Ca2+ and secretion. Our principal findings were: all treatments that increased secretion, correspondingly increased the changes that precede degranulation. These early events correlated with the degree of aggregation of the receptors even when the stimulatory conditions resulted in maximal secretion. Although the results were insufficient to prove that the hydrolysis of inositol phospholipids is required for the rise in cytosolic Ca2+, the studies with D2O and other observations supported this view. Since a plasma-membrane ion channel for Ca2+ has been implicated in the IgE-mediated rise in cytosolic Ca2+ in RBL 2H3 cells, this in turn suggests a heretofore undescribed role for hydrolysis of inositol phospholipids.

  18. Abnormal clearance of soluble aggregates of human immunoglobulin G in patients with systemic lupus erythematosus.

    PubMed

    Lobatto, S; Daha, M R; Breedveld, F C; Pauwels, E K; Evers-Schouten, J H; Voetman, A A; Cats, A; Van Es, L A

    1988-04-01

    In the present study, we tested mononuclear phagocyte system function in nine healthy controls and 15 SLE patients with complement activating 123I-labelled aggregates of human IgG (AIgG). Clearance half-time of AIgG was 26 +/- 8 min in controls, compared to 58 +/- 27 min in patients (P less than 0.005). Binding of AIgG to erythrocytes was significantly lower in patients, 9.3 +/- 8.1 vs 24 +/- 20% (P less than 0.05). The increase of C3a-levels in plasma was significantly lower in patients than in controls (P less than 0.05 at 3 and 8 min), suggesting less complement activation. Liver and spleen uptake of 123I-AIgG was measured with a gamma camera and expressed as liver/spleen uptake ratios. In patients, the liver/spleen uptake ratios were significantly higher than in controls at 15 min, 3.8 +/- 2.0 vs 2.31 +/- 0.7 (P less than 0.05), due to less splenic uptake of AIgG. Correlations between clearance half-time or liver/spleen uptake ratios and immune complex levels or disease activity were not found. This study indicates that clearance of soluble AIgG is abnormal in patients with SLE, due to decreased splenic uptake of AIgG.

  19. Conformational and Colloidal Stabilities of Human Immunoglobulin G Fc and Its Cyclized Variant: Independent and Compensatory Participation of Domains in Aggregation of Multidomain Proteins.

    PubMed

    Yageta, Seiki; Shibuya, Risa; Imamura, Hiroshi; Honda, Shinya

    2017-03-06

    Monoclonal immunoglobulin G (IgG) is a multidomain protein. It has been reported that the conformational and colloidal stabilities of each domain are different, and it is predicted that limited domains participate in IgG aggregation. In contrast, the influence of interdomain interactions on IgG aggregation remains unclear. The fragment crystallizable (Fc) region is also a multidomain protein consisting of two sets of CH2 and CH3 domains. Here, we have analyzed the conformational change and aggregate size of an aglycosylated Fc region induced by both acid and salt stresses and have elucidated the influence of interdomain interactions between CH2 and CH3 domains on the conformational and colloidal stabilities of the aglycosylated Fc region. Singular value decomposition analyses demonstrated that the CH2 and CH3 domains unfolded almost independently from each other in the aglycosylated Fc region. Meanwhile, the colloidal stabilities of the CH2 and CH3 domains affect the aggregation process of the unfolded aglycosylated Fc region in a compensatory way. Moreover, the influence of an additional interdomain disulfide bond, introduced at the C-terminal end of the CH3 domains to produce the Fc variant, cyclized Fc, was evaluated. This interdomain disulfide bond increased the conformational stability of the CH3 domain. The stabilization of the CH3 domain in the cyclized Fc successfully improved aggregation tolerance following acid stress, although the sizes of aggregates produced were comparable to those of the aglycosylated Fc region.

  20. The high-affinity immunoglobulin E receptor (FcepsilonRI) regulates mitochondrial calcium uptake and a dihydropyridine receptor-mediated calcium influx in mast cells: Role of the FcepsilonRIbeta chain immunoreceptor tyrosine-based activation motif.

    PubMed

    Suzuki, Yoshihiro; Yoshimaru, Tetsuro; Inoue, Toshio; Nunomura, Satoshi; Ra, Chisei

    2008-04-01

    A growing body of evidence suggests that mitochondria take up calcium upon receptor (agonist) stimulation and that this contributes to the dynamics of spatiotemporal calcium signaling. We have previously shown that engagement of the high-affinity receptor for immunoglobulin E (FcepsilonRI) stimulates mitochondrial calcium ([Ca2+]m) uptake in mast cells. The present study was undertaken to investigate the mechanisms and biological significance of FcepsilonRI regulation of [Ca2+]m. Antigen stimulated [Ca2+]m uptake in a dose-dependent manner with a minimal effective dose of 0.03-3 ng/ml. This [Ca2+]m uptake took place immediately, reaching its peak within minutes and was inhibited by the src family kinase inhibitor PP1 and phosphatidylinositol-3-kinase inhibitor wortmannin. Analyses using mast cells expressing the wild-type or the mutated type of the FcepsilonRIbeta immunoreceptor tyrosine-based activation motif (ITAM) in which all tyrosine residues were replaced by phenylalanine revealed that the FcepsilonRIbeta ITAM is essential for a sustained [Ca2+]m uptake. The FcepsilonRIbeta ITAM was essential for overall calcium response upon weak FcepsilonRI stimulation (at low antigen concentration), while upon strong stimulation (at high antigen concentration) it appeared necessary selectively to an immediate calcium response that was sensitive to the dihydropyridine receptor (DHPR) antagonist nifedipine and wortmannin but not to the store-operated calcium entry (SOCE) antagonists such as 2-aminoethoxyphenyl borate and SK&F96365. These data demonstrate that the FcepsilonRIbeta regulates [Ca2+]m uptake in mast cells via the ITAM and suggest that this plays a key role in regulating calcium influx especially that induced via a DHPR-mediated calcium channel.

  1. Aggregation of Full-length Immunoglobulin Light Chains from Systemic Light Chain Amyloidosis (AL) Patients Is Remodeled by Epigallocatechin-3-gallate.

    PubMed

    Andrich, Kathrin; Hegenbart, Ute; Kimmich, Christoph; Kedia, Niraja; Bergen, H Robert; Schönland, Stefan; Wanker, Erich; Bieschke, Jan

    2017-02-10

    Intervention into amyloid deposition with anti-amyloid agents like the polyphenol epigallocatechin-3-gallate (EGCG) is emerging as an experimental secondary treatment strategy in systemic light chain amyloidosis (AL). In both AL and multiple myeloma (MM), soluble immunoglobulin light chains (LC) are produced by clonal plasma cells, but only in AL do they form amyloid deposits in vivo We investigated the amyloid formation of patient-derived LC and their susceptibility to EGCG in vitro to probe commonalities and systematic differences in their assembly mechanisms. We isolated nine LC from the urine of AL and MM patients. We quantified their thermodynamic stabilities and monitored their aggregation under physiological conditions by thioflavin T fluorescence, light scattering, SDS stability, and atomic force microscopy. LC from all patients formed amyloid-like aggregates, albeit with individually different kinetics. LC existed as dimers, ∼50% of which were linked by disulfide bridges. Our results suggest that cleavage into LC monomers is required for efficient amyloid formation. The kinetics of AL LC displayed a transition point in concentration dependence, which MM LC lacked. The lack of concentration dependence of MM LC aggregation kinetics suggests that conformational change of the light chain is rate-limiting for these proteins. Aggregation kinetics displayed two distinct phases, which corresponded to the formation of oligomers and amyloid fibrils, respectively. EGCG specifically inhibited the second aggregation phase and induced the formation of SDS-stable, non-amyloid LC aggregates. Our data suggest that EGCG intervention does not depend on the individual LC sequence and is similar to the mechanism observed for amyloid-β and α-synuclein.

  2. Spray-drying of proteins: effects of sorbitol and trehalose on aggregation and FT-IR amide I spectrum of an immunoglobulin G.

    PubMed

    Maury, Michael; Murphy, Keith; Kumar, Sandeep; Mauerer, Alexander; Lee, Geoffrey

    2005-02-01

    An immunoglobulin G (IgG) was spray-dried on a Buchi 190 laboratory spray-dryer at inlet and outlet air temperatures of 130 and 190 degrees C, respectively. The IgG solution contains initially 115 mg/ml IgG plus 50 mg/ml sorbitol. After dialysis, at least 80% of low molecular weight component was removed. After spray-drying the dialyzed IgG and immediate redissolution of the powder, an increase in aggregates from 1 to 17% occurred. A major shift towards increase beta-sheet structure was detected in the spray-dried solid, which, however, reverted to native structure on redissolution of the powder. A correlation between aggregation determined by size exclusion chromatography and alterations in secondary structure determined by Fourier transformation infra-red spectroscopy could not therefore be established. On spray-drying a non-dialyzed, sorbitol-containing IgG only some 0.7% aggregates were formed. The sorbitol is therefore evidently able to stabilize partially the IgG during the process of spray-drying. Addition of trehalose to the liquid feed produced quantitatively the same stabilizing action on the IgG during spray-drying as did the sorbitol. This finding again points towards a water replacement stabilization mechanism. The IgG spray-dried powder prepared from the dialyzed liquid feed showed continued substantial aggregation on dry storage at 25 degrees C. This was substantially less in the non-dialyzed, sorbitol-containing spray-dried powder. Addition of trehalose to both dialyzed and non-dialyzed system produced substantial improvement in storage stability and reduction in aggregate formation in storage. The quantitative stabilizing effect of the trehalose was only slightly higher than that of the sorbitol. Taken together, these results indicate that both the sorbitol and trehalose stabilize the IgG primarily by a water replacement mechanism rather than by glassy immobilization. The relevance of this work is its questioning of the importance of the usually

  3. Visualizing clathrin-mediated IgE receptor internalization by electron and atomic force microscopy.

    PubMed

    Burns, Alan R; Oliver, Janet M; Pfeiffer, Janet R; Wilson, Bridget S

    2008-01-01

    A significant step in the immunoglobulin E (IgE) receptor signaling pathway in mast cell membranes is receptor internalization by clathrin-coated vesicles. Visualization in native membrane sheets of the emerging clathrin lattice structures containing the IgE receptor and associated signaling partners has been accomplished with high-resolution transmission electron microscopy (TEM). More recently, membrane sheets with labeled clathrin have also been characterized with atomic force microscopy (AFM) in combination with fluorescence imaging. We discuss here the procedure for creating fixed, native cell membrane sheets, labeling with immunogold or fluorescent labels, and utilization for TEM or AFM/fluorescence imaging of clathrin-mediated IgE internalization.

  4. Elucidation of Acid-induced Unfolding and Aggregation of Human Immunoglobulin IgG1 and IgG2 Fc

    PubMed Central

    Latypov, Ramil F.; Hogan, Sabine; Lau, Hollis; Gadgil, Himanshu; Liu, Dingjiang

    2012-01-01

    Understanding the underlying mechanisms of Fc aggregation is an important prerequisite for developing stable and efficacious antibody-based therapeutics. In our study, high resolution two-dimensional nuclear magnetic resonance (NMR) was employed to probe structural changes in the IgG1 Fc. A series of 1H-15N heteronuclear single-quantum correlation NMR spectra were collected between pH 2.5 and 4.7 to assess whether unfolding of CH2 domains precedes that of CH3 domains. The same pH range was subsequently screened in Fc aggregation experiments that utilized molecules of IgG1 and IgG2 subclasses with varying levels of CH2 glycosylation. In addition, differential scanning calorimetry data were collected over a pH range of 3–7 to assess changes in CH2 and CH3 thermostability. As a result, compelling evidence was gathered that emphasizes the importance of CH2 stability in determining the rate and extent of Fc aggregation. In particular, we found that Fc domains of the IgG1 subclass have a lower propensity to aggregate compared with those of the IgG2 subclass. Our data for glycosylated, partially deglycosylated, and fully deglycosylated molecules further revealed the criticality of CH2 glycans in modulating Fc aggregation. These findings provide important insights into the stability of Fc-based therapeutics and promote better understanding of their acid-induced aggregation process. PMID:22084250

  5. Fish Immunoglobulins

    PubMed Central

    Mashoof, Sara; Criscitiello, Michael F.

    2016-01-01

    The B cell receptor and secreted antibody are at the nexus of humoral adaptive immunity. In this review, we summarize what is known of the immunoglobulin genes of jawed cartilaginous and bony fishes. We focus on what has been learned from genomic or cDNA sequence data, but where appropriate draw upon protein, immunization, affinity and structural studies. Work from major aquatic model organisms and less studied comparative species are both included to define what is the rule for an immunoglobulin isotype or taxonomic group and what exemplifies an exception. PMID:27879632

  6. Non-immunospecific association of immunoglobulin G with chromatin during elution from protein A inflates host contamination, aggregate content, and antibody loss.

    PubMed

    Gagnon, Pete; Nian, Rui; Yang, Yuansheng; Yang, Qiaohui; Lim, Chiew Ling

    2015-08-21

    Monoclonal IgG at pH 3.5 expressed a tendency to self-associate and associate non-specifically with surfaces, including the surfaces of precipitated chromatin heteroaggregates. The tendency was elevated with protein A-eluted IgG still in elution buffer (100mM acetate, pH 3.5). Association of IgG with chromatin elements under protein A elution conditions amplified host protein contamination of the elution fraction about 15-fold, caused formation of aggregates that persisted after pH neutralization, and imposed an approximate 5% loss on IgG recovery. Neutralization released eluted IgG from its low pH associations with chromatin and caused heteroaggregate remnants to associate into large particles easily removed by microfiltration. Most effective host contaminant clearance was achieved by filtration after neutralization to pH 5.5. All chromatin-mediated liabilities were suspended by extraction of chromatin heteroaggregates in advance of protein A.

  7. Feline immunoglobulins.

    PubMed

    Schultz, R D; Scott, F W; Duncan, J R; Gillespie, J H

    1974-02-01

    Immunoglobulins (Ig) in feline sera and secretions were identified by immuno-electrophoresis and immunodiffusion with rabbit antisera prepared to feline IgG, IgA, IgM, and whole serum. Adult cat sera, colostral whey, postcolostral sera, tears, and nasal secretions contained IgG, IgA, and IgM. IgG was the only Ig identified in precolostral sera and cerebrospinal fluid. Milk, intestinal contents, pooled allantoic and amniotic fluids, and saliva from adult cats and urine from suckling kittens contained IgG and IgA. Ig were not detected in urine from adult cats. Bile was unique in that IgA and IgM were the predominant Ig.

  8. Apolipoprotein E receptor pathways in Alzheimer disease.

    PubMed

    Schmidt, Vanessa; Carlo, Anne-Sophie; Willnow, Thomas E

    2014-01-01

    Alzheimer disease (AD) is the most common neurodegenerative disease affecting millions of patients worldwide. According to the amyloid cascade hypothesis, the formation of neurotoxic oligomers composed of amyloid-β (Aβ) peptides is the main mechanism that causes synaptic dysfunction and, eventually, neuronal cell death in this condition. Intriguingly, apolipoprotein E (apoE), the most important genetic risk factor for sporadic AD, emerges as a key factor that contributes to many aspects of the amyloid cascade including the clearance of Aβ from brain interstitial fluid and the ability of this peptide to form neurotoxic oligomers. Central to the activity of apoE in the healthy and in the diseased brain are apoE receptors that interact with this protein to mediate its multiple cellular and systemic effects. This review describes the molecular interactions that link apoE and its cellular receptors with neuronal viability and function, and how defects in these pathways in the brain promote neurodegeneration. For further resources related to this article, please visit the WIREs website. The authors have declared no conflicts of interest for this article. © 2014 Wiley Periodicals, Inc.

  9. Quantitative immunoglobulins in adulthood.

    PubMed

    Crisp, Howard C; Quinn, James M

    2009-01-01

    Although age-related changes in serum immunoglobulins are well described in childhood, alterations in immunoglobulins in the elderly are less well described and published. This study was designed to better define expected immunoglobulin ranges and differences in adults of differing decades of life. Sera from 404 patients, aged 20-89 years old were analyzed for quantitative immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA). The patients with diagnoses or medications known to affect immunoglobulin levels were identified while blinded to their immunoglobulin levels. A two-factor ANOVA was performed using decade of life and gender on both the entire sample population as well as the subset without any disease or medication expected to alter immunoglobulin levels. A literature review was also performed on all English language articles evaluating quantitative immunoglobulin levels in adults >60 years old. For the entire population, IgM was found to be higher in women when compared with men (p < 0.001) and lower in the oldest sample population compared with the youngest population (p < 0.001). For the population without diseases known to affect immunoglobulin levels, the differences in IgM with gender and age were maintained (p < or = 0.001) and IgA levels were generally higher in the older population when compared with the younger population (p = 0.009). Elderly patients without disease known to affect immunoglobulin levels have higher serum IgA levels and lower serum IgM levels. Women have higher IgM levels than men throughout life. IgG levels are not significantly altered in an older population.

  10. Immunoglobulin E in histoplasmosis.

    PubMed Central

    Cox, R A; Arnold, D R

    1980-01-01

    Immunoglobulin M, G, A, and E serum levels were quantitated in 20 patients with active histoplasmosis (group I), 24 healthy subjects who were skin test positive to histoplasmin (group II), and 47 healthy persons who were skin test negative to histoplasmin (group III). The results established that patients with this disease have increased immunoglobulin G (P less than 0.05), immunoglobulin A (P less than 0.001), and immunoglobulin E (P less than 0.01) serum levels when compared with the 71 healthy subjects in groups II and III. PMID:7399706

  11. Apolipoprotein E and Apolipoprotein E Receptors: Normal Biology and Roles in Alzheimer Disease

    PubMed Central

    Holtzman, David M.; Herz, Joachim; Bu, Guojun

    2012-01-01

    Apolipoprotein E (APOE) genotype is the major genetic risk factor for Alzheimer disease (AD); the ε4 allele increases risk and the ε2 allele is protective. In the central nervous system (CNS), apoE is produced by glial cells, is present in high-density-like lipoproteins, interacts with several receptors that are members of the low-density lipoprotein receptor (LDLR) family, and is a protein that binds to the amyloid-β (Aβ) peptide. There are a variety of mechanisms by which apoE isoform may influence risk for AD. There is substantial evidence that differential effects of apoE isoform on AD risk are influenced by the ability of apoE to affect Aβ aggregation and clearance in the brain. Other mechanisms are also likely to play a role in the ability of apoE to influence CNS function as well as AD, including effects on synaptic plasticity, cell signaling, lipid transport and metabolism, and neuroinflammation. ApoE receptors, including LDLRs, Apoer2, very low-density lipoprotein receptors (VLDLRs), and lipoprotein receptor-related protein 1 (LRP1) appear to influence both the CNS effects of apoE as well as Aβ metabolism and toxicity. Therapeutic strategies based on apoE and apoE receptors may include influencing apoE/Aβ interactions, apoE structure, apoE lipidation, LDLR receptor family member function, and signaling. Understanding the normal and disease-related biology connecting apoE, apoE receptors, and AD is likely to provide novel insights into AD pathogenesis and treatment. PMID:22393530

  12. Clinical use of immunoglobulins.

    PubMed

    McClelland, D B; Yap, P L

    1984-02-01

    The use of immunoglobulins for prophylaxis and therapy are reviewed. Normal and hyperimmune immunoglobulins have well established clinical applications. These are summarized in Table 14. This form of therapy has now entered a period of rapid change due to the availability of human immunoglobulins which are safe for intravenous use, permitting large doses to be given rapidly. This will permit reappraisal of many conventional applications and exploration of new possibilities for the use of these products. The approaching wide availability of monoclonal antibodies for clinical use will open up a further wide range of new therapeutic applications, providing that concerns over the products' safety are allayed .

  13. Equine immunoglobulins and organization of immunoglobulin genes.

    PubMed

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

    2015-12-01

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

  14. Release of leukotrienes C4 and B4 (LTC4, LTB4) and prostaglandin E2 (PGE2) from human monocytes (M phi) induced with aggregated immunoglobulins (Ig) of different classes

    SciTech Connect

    Ferreri, N.R.; Howland, W.C.; Spiegelberg, H.L.

    1986-03-01

    Purified human peripheral blood monocytes were stimulated with aggregated human myeloma proteins or the calcium ionophore A23187. Release of LTC4, LTB4 and PGE2 into the supernate was determined by radioimmunoassay and high performance liquid chromatography. The ionophore induced release of 10 +/- 5 ng LTC4 and 25 +/- 8 ng LTB4/10/sup 6/ M phi. Aggregated IgG, IgA and IgE but not IgM or monomeric Ig induced release of LTC4 and LTB4 that was approximately 10-20% of that induced by ionophore. Similarly, IgG, IgA and IgE but not IgM induced release of PGE2 (range 0.015-0.22 ng/10/sup 6/ M phi). Absence of calcium or preincubation with nordihydroguaiaretic acid (10/sup -6/ M) inhibited Ig-induced LTC4 and LTB4 release and indomethacin (10/sup -6/ M) inhibited PGE2 release. Phagocytosis of the Ig aggregates was not required since release was not inhibited by cytochalasin B. Release of PGE2 and LTC4/LTB4 induced by all classes except IgM correlated with the presence or absence of M phi Fc receptors (FcR) for each class as determined by rosette assay. The data indicate that IgG, IgA and IgE immune complexes can induce M phi arachidonic acid metabolism via interaction with FcR despite inhibition of phagocytosis. Such a mechanism may contribute to inflammatory reactions characterized by mononuclear cell infiltrates.

  15. Immunoglobulin in intestinal secretions.

    PubMed

    Cutropia de Guirao, C

    1977-12-01

    The objective of the present investigation is the study and interpretation of the role played by the immunoglobulins, especially IgA, during acute diarrhea in children. IgA, IGG and IgM values in serum and IgA in intestinal secretions were studied in a group of children (between 3 months and 5 years of age) during diarrhea, convalescence and in normals. The method of simple radial immunodiffusion according to Mancini was employed. IgA is the immunoglobulin which suffers the greastest alteration in acute diarrhea. The precipitation halos (the average values), were lower during the diarrhea than in convalescence and in normals.

  16. Prostaglandin E receptors as inflammatory therapeutic targets for atherosclerosis.

    PubMed

    Yang, Cui; Liu, Xiuxia; Cao, Qing; Liang, Qian; Qiu, Xiaohua

    2011-01-31

    Prostaglandin E receptors (EPs) are the G-protein-coupled receptors (GPCRs) that respond to type E(2) prostaglandin (PGE(2)). Data has shown that PGE(2) may function as an endogenous anti-inflammatory mediator by suppressing the production of cytokines. However, other studies have demonstrated that PGE(2), a pro-inflammatory mediator produced by various cell types within the wounded vascular wall, plays a crucial role in early atherosclerotic development. These contradictory results may be due to the versatility of EPs. Experimental data suggest an individual role for each PGE(2) receptor, such as EP(1), EP(2), EP(3) and EP(4), in atherosclerosis. In this review, the roles of EPs in atherosclerosis are summarized, and the value of EPs as new therapeutic targets for atherosclerosis is explored.

  17. Domain metastability: a molecular basis for immunoglobulin deposition?

    PubMed

    Sonnen, Andreas F-P; Yu, Chao; Evans, Edward J; Stuart, David I; Davis, Simon J; Gilbert, Robert J C

    2010-06-04

    We present the crystal structure of an immunoglobulin light-chain-like domain, CTLA-4, as a strand-swapped dimer displaying cis-trans proline isomerisation and native-like hydrogen bonding. We also show that CTLA-4 can form amyloid-like fibres and amorphous deposits explainable by the same strand swapping. Our results suggest a molecular basis for the pathological aggregation of immunoglobulin domains and why amyloid-like fibres are more often composed of homologous rather than heterologous subunits. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  18. [Selective immunoglobulin A deficiency].

    PubMed

    Binek, Alicja; Jarosz-Chobot, Przemysława

    2012-01-01

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

  19. THE IMMUNOGLOBULINS OF MICE

    PubMed Central

    Fahey, John L.; Wunderlich, John; Mishell, Robert

    1964-01-01

    Two classes of 7S γ-globulins are identified in normal mouse serum and are designated 7S γ2-globulins and 7S γ1-globulins. These two immunoglobulin classes are similar in size. They differ in range of electrophoretic mobility, in specific antigenic determinants, and in genetically determined isoantigens. Four classes of immunoglobulins in mouse serum, i.e. 7S γ2-, 7S γ1-, γ1A (β2A), and γM-globulins, were shown to have antibody activity. Each class was characterized and shown to have distinctive immunochemical and physicochemical properties. The genetically determined isoantigens, Iga-1 and Iga-2, were shown to be present only on 7S γ2-globulin molecules. PMID:14208249

  20. [Avidity of polyreactive immunoglobulins].

    PubMed

    Bobrovnik, S A

    2014-01-01

    An analysis of the mechanism of interaction between polyreactive immunoglobulins (PRIG) and antigen was conducted and it was shown that most of the traditional methods of antibody affinity evaluation are not applicable for PRIG affinity. The comparative assessment of the mouse and human PRIG avidity against ovalbumin and horse myoglobin and the avidity of specific monoclonal antibodies against ovalbumin have shown that the avidity of PRIG not only is much less than the avidity of monoclonal antibodies but even exceeds it.

  1. Immunoglobulin genes of the turtles.

    PubMed

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

    2013-03-01

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

  2. The discovery of immunoglobulin E.

    PubMed

    Ribatti, Domenico

    2016-03-01

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

  3. [Blood serum immunoglobulins in thyrotoxicosis].

    PubMed

    Epishin, A V

    1978-01-01

    Serum immunoglobulin content was determined in 85 patients with thyrotoxicosis and in 80 healthy persons by radial immunodiffusion in agar after Mancini by means of monospecific antisera (made at the N. F. Gamaleya Institute of Epidemiology immunoglobulins of classes G and M. The most pronounced increase was noted in patients with severe and moderate thyrotoxicosis.

  4. Construction aggregates

    USGS Publications Warehouse

    Tepordei, V.V.

    1995-01-01

    Part of the 1994 Industrial Minerals Review. The production, consumption, and applications of construction aggregates are reviewed. In 1994, the production of construction aggregates, which includes crushed stone and construction sand and gravel combined, increased 7.7 percent to 2.14 Gt compared with the previous year. These record production levels are mostly a result of funding for highway construction work provided by the Intermodal Surface Transportation Efficiency Act of 1991. Demand is expected to increase for construction aggregates in 1995.

  5. THE IMMUNOGLOBULINS OF MICE

    PubMed Central

    Fahey, John L.; Wunderlich, John; Mishell, Robert

    1964-01-01

    Two subclasses of mouse 7S γ2-globulins are identified, and are designated γ2a- and γ2b-globulins. They are distinguished from 7S γ1-globulins, γ1A (β2A)-globulins, and γ1M-globulins of mouse serum. Antibody activity was detected among the γ2a-globulins and γ2b-globulins of hyperimmune mouse serum. γ2a- and γ2b-myeloma proteins were identified. The genetically determined isoantigen, Iga-1, was present on γ2a-myeloma proteins, but not on γ2b-myeloma proteins. These findings indicate a complexity among the 7S γ2-globulins which must be taken into account in structural, functional, and genetic studies of immunoglobulins. PMID:14206439

  6. Milk immunoglobulins and complement factors.

    PubMed

    Korhonen, H; Marnila, P; Gill, H S

    2000-11-01

    The importance of colostrum for the growth and health of newborn offspring is well known. In bovine colostrum, the antibody (immunoglobulin) complement system provides a major antimicrobial effect against a wide range of microbes and confers passive immunity until the calf's own immune system has matured. Bovine serum and lacteal secretions contain three major classes of immunoglobulins: IgG, IgM and IgA. The immunoglobulins are selectively transported from the serum into the mammary gland, as a result of which the first colostrum contains very high concentrations of immunoglobulins (40-200 mg/ml). IgG1 accounts for over 75 % of the immunoglobulins in colostral whey, followed by IgM, IgA and IgG2. All these immunoglobulins decrease within a few days to a total immunoglobulin concentration of 0.7-1.0 mg/ml, with IgG1 representing the major Ig class in milk throughout the lactation period. Together with the antibodies absorbed from colostrum after birth, the complement system plays a crucial role in the passive immunisation of the newborn calf. The occurrence of haemolytic or bactericidal complement activity in bovine colostrum and milk has been demonstrated in several studies. This review deals with the characteristics of bovine Igs and the complement system to be exploited as potential ingredients for health-promoting functional foods.

  7. Construction aggregates

    USGS Publications Warehouse

    Tepordei, V.V.

    1994-01-01

    Part of a special section on industrial minerals in 1993. The 1993 production of construction aggregates increased 6.3 percent over the 1992 figure, to reach 2.01 Gt. This represents the highest estimated annual production of combined crushed stone and construction sand and gravel ever recorded in the U.S. The outlook for construction aggregates and the issues facing the industry are discussed.

  8. Guinea pig hippocampal 5-HT(1E) receptors: a tool for selective drug development.

    PubMed

    Klein, Michael T; Teitler, Milt

    2009-04-01

    Recent studies have indicated that the serotonin [5-hydroxytryptamine (5-HT)] 1E receptor, originally discovered in human brain tissue, is not expressed in rat or mouse brain. Thus, there have been few reports on 5-HT(1E) receptor drug development. However, expression of 5-HT(1E) receptor mRNA has been shown in guinea pig brain. To establish this species as an animal model for 5-HT(1E) drug development, we identified brain regions that exhibit 5-carboxyamidotryptamine, ritanserin, and LY344864 - insensitive [(3)H]5-HT binding (characteristic of the 5-HT(1E) receptor). In hippocampal homogenates, where 5-HT(1E) receptor density was sufficiently high for radioligand binding analysis, 100 nM 5-carboxyamidotryptamine, 30 nM ritanserin, and 100 nM LY344864 were used to mask [(3)H]5-HT binding at non-5-HT(1E) receptors. The K(d) of [(3)H]5-HT was 5.7 +/- 0.7 nM and is indistinguishable from the cloned receptor K(d) of 6.5 +/- 0.6 nM. The affinities of 16 drugs for the cloned and hippocampal-expressed guinea pig 5-HT(1E) receptors are essentially identical (R(2) = 0.97). These findings indicate that using these conditions autoradiographical distribution and signal transduction studies of the 5-HT(1E) receptor in guinea pig brain are feasible. Using the guinea pig as an animal model should provide important insights into possible functions of this receptor and the therapeutic potential of selective human 5-HT(1E) drugs.

  9. Immunoglobulin levels of vitiligo patients.

    PubMed

    Ali, Rubaiya; Ahsan, Mohammad Shamsul; Azad, Mohammad Abul Kalam; Ullah, Md Ashik; Bari, Wasimul; Islam, Sheikh Nazrul; Yeasmin, Sabina; Hasnat, Abul

    2010-01-01

    In the present study, the serum immunoglobulin profiles of vitiligo patients were compared with that of cohort control and evaluated the correlation between immunoglobulin level with their socioeconomic factors and nutritional status. Thirty vitiligo patients were recruited randomly from the Department of Dermatology and Venereology, Bangabandhu Sheikh Mujib Medical University Hospital, Dhaka, Bangladesh for this study. Thirty healthy individuals as control group matched by age, sex, education and socioeconomic factors to the patient group were selected. Serum immunoglobulin concentrations were determined by turbidimetry method using immunoglobulin kit. The concentration of IgG and IgA decreased significantly (P<0.05), but the change of IgM was not significant. Socioeconomic data revealed that most of the patients were young and female. Moreover statistical analysis revealed that there was significant correlation between immunoglobulin (IgG and IgA only) concentrations and BMI and number of depigmented patches with IgG concentrations. Finally it can be concluded that the change of serum immunoglobulin concentration in vitiligo patients could be due to the disease condition as pathomechanism suggested the aberrations in cellular immunity. But study with larger number of population is required for further evaluation of the relationship between the immune response and disease state to confirm these findings.

  10. Soluble IgE receptors--elements of the IgE network.

    PubMed

    Platzer, Barbara; Ruiter, Floortje; van der Mee, John; Fiebiger, Edda

    2011-12-30

    Soluble isoforms of three human IgE Fc receptors, namely FcεRI, FcεRII, and galectin-3, can be found in serum. These soluble IgE receptors are a diverse family of proteins unified by the characteristic of interacting with IgE in the extracellular matrix. A truncated form of the alpha-chain of FcεRI, the high affinity IgE receptor, has recently been described as a soluble isoform (sFcεRI). Multiple soluble isoforms of CD23 (sCD23), the low affinity IgE receptor also known as FcεRII, are generated via different mechanisms of extracellular and intracellular proteolysis. The second low affinity IgE receptor, galectin-3, only exists as a secretory protein. We here discuss the physiological roles of these three soluble IgE receptors as elements of the human IgE network. Additionally, we review the potential and current use of sFcεRI, sCD23, and galectin-3 as biomarkers in human disease. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Serum immunoglobulins in Nigerian neonates.

    PubMed

    Akinwolere, O A; Akinkugbe, F M; Oyewole, A I; Salimonu, L S

    1989-01-01

    Serum immunoglobulins G, M and A levels were studied in 187 Nigerian neonates. Estimations were done by the radial immunodifusion method of Mancini. Immunoglobulin G shows a fall in value in the first few days of life to about 62% of the value in the last days of the neonatal period. There is however a gradual increase in the level of IgM to about double at the end of the neonatal period. IgA level remained relatively constantly low throughout this period. The effect of maternal education on the levels of immunoglobulins of their neonates was also investigated. This had a positive influence at the secondary educational level, affecting only the IgG and IgA.

  12. [Subcutaneous immunoglobulin substitution and therapy].

    PubMed

    Gulácsy, Vera; Maródi, László

    2011-01-09

    Patients with combined primary immunodeficiency or B-cell deficiency with low serum concentration of immunoglobulin G can be efficiently treated with immunoglobulin G concentrates. From the 1950s IgG was used intramuscularly, and from the 1980s intravenous immunoglobulin (IVIG) replacement has become widely available for replacement therapy. Among the potential side effects of IVIG (including anaphylaxis), further disadvantages of IVIG are hospitalization during treatment and varying concentrations of IgG. Over the past ten years, subcutaneous IgG (SCIG) preparations have become reasonable alternatives to IVIG. SCIG given weekly assures a more balanced serum IgG level, side affects are mostly local and temporary; systemic, severe adverse events have not been observed. In addition, SCIG can be used for home treatment of patients which improves their quality of life remarkably.

  13. Aggregation kinetics and structure of cryoimmunoglobulins clusters

    NASA Astrophysics Data System (ADS)

    Spirito, M. De; Chiappini, R.; Bassi, F. Andreasi; Stasio, E. Di; Giardina, B.; Arcovito, G.

    2002-02-01

    Cryoimmunoglobulins are pathological antibodies characterized by a temperature-dependent reversible insolubility. Rheumatoid factors (RF) are immunoglobulins possessing anti-immunoglobulin activity and usually consist of an IgM antibody that recognizes IgG as antigen. These proteins are present in sera of patients affected by a large variety of different pathologies, such as HCV infection, neoplastic and autoimmune diseases. Aggregation and precipitation of cryoimmunoglobulins, leading to vasculiti, are physical phenomena behind such pathologies. A deep knowledge of the physico-chemical mechanisms regulating such phenomena plays a fundamental role in biological and clinical applications. In this work, a preliminary investigation of the aggregation kinetics and of the final macromolecular structure of the aggregates is presented. Through static light scattering techniques, the gyration radius Rg and the fractal dimension Dm of the growing clusters have been determined. However, while the initial aggregation mechanism could be described using the universal reaction-limited cluster-cluster aggregation (RLCCA) theory, at longest times from the beginning of the process, the RLCCA theory fails and a restructuring of clusters is observed together with an increase of the cluster fractal dimension Dm up to a value Dm∼3. The time tn, at which the restructuring takes place, and the final cluster size can be modulated by varying the quenching temperature.

  14. Construction aggregates

    USGS Publications Warehouse

    Tepordei, V.V.

    1996-01-01

    Part of the Annual Commodities Review 1995. Production of construction aggregates such as crushed stone and construction sand and gravel showed a marginal increase in 1995. Most of the 1995 increases were due to funding for highway construction work. The major areas of concern to the industry included issues relating to wetlands classification and the classification of crystalline silica as a probable human carcinogen. Despite this, an increase in demand is anticipated for 1996.

  15. Construction aggregates

    USGS Publications Warehouse

    Nelson, T.I.; Bolen, W.P.

    2007-01-01

    Construction aggregates, primarily stone, sand and gravel, are recovered from widespread naturally occurring mineral deposits and processed for use primarily in the construction industry. They are mined, crushed, sorted by size and sold loose or combined with portland cement or asphaltic cement to make concrete products to build roads, houses, buildings, and other structures. Much smaller quantities are used in agriculture, cement manufacture, chemical and metallurgical processes, glass production and many other products.

  16. Construction aggregates

    USGS Publications Warehouse

    Tepordei, V.V.

    1993-01-01

    Part of a special section on the market performance of industrial minerals in 1992. Production of construction aggregates increased by 4.6 percent in 1992. This increase was due, in part, to the increased funding for transportation and infrastructure projects. The U.S. produced about 1.05 Gt of crushed stone and an estimated 734 Mt of construction sand and gravel in 1992. Demand is expected to increase by about 5 percent in 1993.

  17. The interactions of calreticulin with immunoglobulin G and immunoglobulin Y.

    PubMed

    Møllegaard, Karen Mai; Duus, Karen; Træholt, Sofie Dietz; Thaysen-Andersen, Morten; Liu, Yan; Palma, Angelina S; Feizi, Ten; Hansen, Paul R; Højrup, Peter; Houen, Gunnar

    2011-07-01

    Calreticulin is a chaperone of the endoplasmic reticulum (ER) assisting proteins in achieving the correctly folded structure. Details of the binding specificity of calreticulin are still a matter of debate. Calreticulin has been described as an oligosaccharide-binding chaperone but data are also accumulating in support of calreticulin as a polypeptide binding chaperone. In contrast to mammalian immunoglobulin G (IgG), which has complex type N-glycans, chicken immunoglobulin Y (IgY) possesses a monoglucosylated high mannose N-linked glycan, which is a ligand for calreticulin. Here, we have used solid and solution-phase assays to analyze the in vitro binding of calreticulin, purified from human placenta, to human IgG and chicken IgY in order to compare the interactions. In addition, peptides from the respective immunoglobulins were included to further probe the binding specificity of calreticulin. The experiments demonstrate the ability of calreticulin to bind to denatured forms of both IgG and IgY regardless of the glycosylation state of the proteins. Furthermore, calreticulin exhibits binding to peptides (glycosylated and non-glycosylated) derived from trypsin digestion of both immunoglobulins. Additionally, calreticulin peptide binding was examined with synthetic peptides covering the IgG Cγ2 domain demonstrating interaction with approximately half the peptides. Our results show that the dominant binding activity of calreticulin in vitro is toward the polypeptide moieties of IgG and IgY even in the presence of the monoglucosylated high mannose N-linked oligosaccharide on IgY.

  18. Proteolysis of lymphocytic surface immunoglobulin.

    PubMed Central

    Hough, D W; McIlroy, B M; Stevenson, G T

    1977-01-01

    Limited proteolysis of lymphocytic surface immunoglobulins in guinea-pig, rabbit and man was investigated by immunofluorescence using conjugated antisera specific for immunoglobulin fragments. The cell surface IgM of guinea pig L2C leukaemic lymphocytes and rabbit blood lymphocytes was cleaved in situ at its hinge region by papain. The Fcmicron fragment remained attached to the membrane and could be stained with the appropriate anti-Fc conjugate. The surface IgD and IgM of human chronic lymphocytic leukaemia cells was cleared from the cell surface by papain, as shown by reagents directed against both Fab and Fc region determinants. This could be due either to proteolytic degradation of membrane bound Fc or to initial cleavage of Ig from the membrane at some point other than the hinge region. PMID:321347

  19. The vectorial release of nascent immunoglobulin peptides

    PubMed Central

    Bevan, Michael J.

    1971-01-01

    A microsomal preparation from a mouse plasmacytoma, MOPC 47A, that secretes immunoglobulin A was used to study the release of nascent immunoglobulin peptides in vitro. Nascent chains were released with puromycin and characterized with specific antiserum against the immunoglobulin product of the tumour. When the tissue had been prelabelled with [3H]leucine the experiments were complicated by the large background of completed radioactive polypeptides in the microsomal preparation. Up to one-third of the released radioactivity in the microsomal preparation could be recognized as immunoglobulin. With [3H]-puromycin as the radioactive label, however, the results are much easier to interpret, although the proportion of released radioactivity that can be identified as immunoglobulin is lower (up to one-tenth). Both types of experiment demonstrate that all of the recognizable nascent immunoglobulin chains remain in association with the microsomal vesicles after release from the ribosomes. PMID:5124814

  20. 7th International Immunoglobulin Conference: Immunoglobulin in clinical practice.

    PubMed

    Shapiro, R S; Borte, M

    2014-12-01

    Intravenous and subcutaneous immunoglobulins (IVIg and SCIg, respectively) are increasingly used in clinical practice, not only as replacement therapy but also for immunomodulation. Physicians have learned that primary immunodeficiency (PID) patients are susceptible to recurrent respiratory tract infections even when appropriately treated with immunoglobulin (Ig) therapy. Further investigation will establish whether a combined therapeutic approach including Ig dose optimization will prevent progressive lung disease in PID. The wear-off effects observed with IVIg can be minimized by adjusting the dosing regimen. It is also possible to avoid the cyclic wear-off following transition to SCIg administration. Consideration of benefit versus risk with Ig therapy includes evaluating the potential occurrence of thromboembolic and haemolytic events, which may be more frequent when Ig is administered in high doses and in the presence of pre-existing risk factors. The ability to select an administration method from IVIg, SCIg or hyaluronidase-facilitated SCIg infusions provides patient choice and alternatives if one or other administration route is not suitable for a patient. The evolution in indications, applications, and understanding of Ig therapy described here has reinforced the need for robust methods to prioritize Ig use.

  1. Immunoglobulins in human aqueous humour.

    PubMed Central

    Sen, D. K.; Sarin, G. S.; Saha, K.

    1977-01-01

    The immunoglobulin concentrations in human aqueous humour from 44 patients aged 35 to 85 years with cataracts were measured by a standard immunodiffusion method. IgG was found in all the samples (mean level 7-0 mg/100 ml. IgD, IgA or IgM could not be detected. There was no significant difference in IgG levels in aqueous humour between the two sexes, in different age groups, and in the different types of cataracts. PMID:403928

  2. A new human mast cell line expressing a functional IgE receptor converts to tumorigenic growth by KIT D816V transfection.

    PubMed

    Saleh, Rosine; Wedeh, Ghaith; Herrmann, Harald; Bibi, Siham; Cerny-Reiterer, Sabine; Sadovnik, Irina; Blatt, Katharina; Hadzijusufovic, Emir; Jeanningros, Sylvie; Blanc, Catherine; Legarff-Tavernier, Magali; Chapiro, Elise; Nguyen-Khac, Florence; Subra, Frédéric; Bonnemye, Patrick; Dubreuil, Patrice; Desplat, Vanessa; Merle-Béral, Hélène; Willmann, Michael; Rülicke, Thomas; Valent, Peter; Arock, Michel

    2014-07-03

    In systemic mastocytosis (SM), clinical problems arise from factor-independent proliferation of mast cells (MCs) and the increased release of mediators by MCs, but no human cell line model for studying MC activation in the context of SM is available. We have created a stable stem cell factor (SCF) -dependent human MC line, ROSA(KIT WT), expressing a fully functional immunoglobulin E (IgE) receptor. Transfection with KIT D816V converted ROSA(KIT WT) cells into an SCF-independent clone, ROSA(KIT D816V), which produced a mastocytosis-like disease in NSG mice. Although several signaling pathways were activated, ROSA(KIT D816V) did not exhibit an increased, but did exhibit a decreased responsiveness to IgE-dependent stimuli. Moreover, NSG mice bearing ROSA(KIT D816V)-derived tumors did not show mediator-related symptoms, and KIT D816V-positive MCs obtained from patients with SM did not show increased IgE-dependent histamine release or CD63 upregulation. Our data show that KIT D816V is a disease-propagating oncoprotein, but it does not activate MCs to release proinflammatory mediators, which may explain why mediator-related symptoms in SM occur preferentially in the context of a coexisting allergy. ROSA(KIT D816V) may provide a valuable tool for studying the pathogenesis of mastocytosis and should facilitate the development of novel drugs for treating SM patients.

  3. Subcutaneous immunoglobulin: opportunities and outlook

    PubMed Central

    Misbah, S; Sturzenegger, M H; Borte, M; Shapiro, R S; Wasserman, R L; Berger, M; Ochs, H D

    2009-01-01

    Immunoglobulin (Ig) administration via the subcutaneous (s.c.) route has become increasingly popular in recent years. The method does not require venous access, is associated with few systemic side effects and has been reported to improve patients' quality of life. One current limitation to its use is the large volumes which need to be administered. Due to the inability of tissue to accept such large volumes, frequent administration at multiple sites is necessary. Most studies conducted to date have investigated the use of subcutaneous immunoglobulin (SCIg) in patients treated previously with the intravenous (i.v.) formulation. New data now support the use of s.c. administration in previously untreated patients with primary immunodeficiencies. SCIg treatment may further be beneficial in the treatment of autoimmune neurological conditions, such as multi-focal motor neuropathy; however, controlled trials directly comparing the s.c. and i.v. routes are still to be performed for this indication. New developments may further improve and facilitate the s.c. administration route. For example, hyaluronidase-facilitated administration increases the bioavailability of SCIg, and may allow for the administration of larger volumes at a single site. Alternatively, more concentrated formulations may reduce the volume required for administration, and a rapid-push technique may allow for shorter administration times. As these developments translate into clinical practice, more physicians and patients may choose the s.c. administration route in the future. PMID:19883424

  4. Blood Test: Immunoglobulin A (IgA)

    MedlinePlus

    ... to 2-Year-Old Blood Test: Immunoglobulin A (IgA) KidsHealth > For Parents > Blood Test: Immunoglobulin A (IgA) Print A A A What's in this article? ... Questions en español Análisis de sangre: inmunoglobulina A (IgA) What It Is An IgA test measures the ...

  5. [Serum immunoglobulin E level in bronchial asthma].

    PubMed

    Denchev, K; Radkov, M; Lipcheva, N

    1976-01-01

    Serum immunoglobulin E level was determined in 50 patients with bronchial asthma, treated in the out-patients department and clinical conditions at the Faculty Hospital--Varna. The quantitative determination of immunoglobulin E was carried out by radial immunodiffusion according to Mancini with monospecific anti-IgE globulin serum from Behringswerke (GFR). A considerable elevation of immunoglobulin E in the patients' sera was found, at an average of 394 IU (control 124 IU). A discrepancy in serum immunoglobulin E level was established with the different clinical forms of asthma. The highest are the values with infectious-allergic astmha-424 IU. High are the values both in the treated and not-treated with corticosteroids, without an essential difference between the two patient groups. Some of the rest immunoglobulins showed also an elevationppIgG 2620 mg% and IgA 366 mg%.

  6. Pharmacoeconomics of immunoglobulins in primary immunodeficiency.

    PubMed

    Simoens, Steven

    2009-08-01

    Primary immunodeficiency disorders are associated with increased patient susceptibility to recurrent infections. Since the 1950s, intramuscular, intravenous and subcutaneous immunoglobulin products have been used to replace functionally deficient or absent immunoglobulins, reduce the incidence of infections and prevent organ damage caused by infections. This article aims to review the use of immunoglobulin therapy in primary immunodeficiency by focusing on costs, effectiveness, cost-effectiveness, supply and off-label use. To date, the economic burden of primary immunodeficiency is unknown. Past studies have supported minimal differences in effectiveness between intravenous and subcutaneous immunoglobulins. Subcutaneous therapy may be considered for patients who prefer treatment at home. The small number of economic evaluations and their methodological limitations precludes the recommendation of a specific product for use in primary immunodeficiency on pharmacoeconomic grounds. Demand for immunoglobulins has increased over time, leading to periodic shortages and emphasizing the importance of its appropriate use.

  7. Immunoglobulin-E reactivity to wine glycoproteins in heavy drinkers.

    PubMed

    Gonzalez-Quintela, Arturo; Gomez-Rial, Jose; Valcarcel, Catalina; Campos, Joaquin; Sanz, Maria-Luisa; Linneberg, Allan; Gude, Francisco; Vidal, Carmen

    2011-03-01

    N-glycans from plant and invertebrate allergens can induce extensive immunoglobulin-E (IgE) cross-reactivity in vitro. IgE antibodies against these N-glycans, also termed cross-reactive carbohydrate determinants or CCDs, are prevalent in alcohol drinkers. This study investigated the prevalence and biological significance of IgE antibodies to N-glycans from wine glycoproteins in heavy drinkers. A structured questionnaire, skin prick tests, serum IgE levels, IgE-immunoblotting to wine extracts, and basophil activation tests were used to characterize 20 heavy drinkers and 10 control subjects. Eleven heavy drinkers (55%) showed IgE binding to proteins in wine extracts. The proteins were identified by mass spectrometry as grape-derived vacuolar invertase and thaumatin-like protein. Immunoblot reactivity was closely associated with the presence of IgE to CCDs and was inhibited by preincubation with a glycoconjugate containing bromelain-type N-glycans. The same conjugate, CCD-bearing allergens, and wine extracts activated basophils in patients with high-titer CCD-specific IgE but not in healthy controls. There was no relationship between immunoblot reactivity and consumption of any specific type of wine. No patient reported symptoms of hypersensitivity to Hymenoptera venom, food, or wine. In conclusion, heavy drinkers frequently show IgE reactivity to the N-glycans of wine glycoproteins. Glycans and wine glycoprotein extracts can induce basophil activation in sensitized alcoholics. The clinical significance of these findings remains to be elucidated.

  8. Studies on immunoglobulin and immunoglobulin-forming cells in Heterodontus japonicus, a cartilaginous fish.

    PubMed

    Tomonaga, S; Kobayashi, K; Hagiwara, K; Sasaki, K; Sezaki, K

    1985-01-01

    Immunoglobulin (Ig), lymphoid tissues and Ig-forming cells of the Japanese bullhead shark, Heterodontus japonicus were analyzed biochemically, histologically and immunocytochemically. The serum of Heterodontus contains two Igs with different molecular weights one with 900 K and the other with 180 K daltons. Heavy chains of the two Igs showed an identical molecular weight of 68 K and the same antigenicity, indicating that the two Igs belong to the same class with different molecular structure. Light chains of Heterodontus Igs showed two distinct bands using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, one with the molecular weight of 25 K and the other with 22 K daltons. The latter finding indicates the possible existence of two light chain types in the Heterodontus Igs. White pulp of the spleen appeared as a well-developed lymphoid tissue accompanied large number of Ig-forming cells especially around blood vessels. Massive lymphocytic aggregations were found in the central area of the intestinal valves and certain lymphoid cells were demonstrated to be Ig-forming cells. Ig-forming cells were also observed in the epigonal organ, although the frequency was much less than in the former two tissues. Although the spleen is the major Ig-forming organ in Heterodontus japonicus, the valvular intestine and the epigonal organ also appear to share the function of Ig production.

  9. Atypical immunoglobulin light chain amyloidosis

    PubMed Central

    Wu, Xia; Feng, Jun; Cao, Xinxin; Zhang, Lu; Zhou, Daobin; Li, Jian

    2016-01-01

    Abstract Background: Primary immunoglobulin light chain amyloidosis (AL amyloidosis) is a plasma cell disorder which mainly affects heart, kidneys, liver, and peripheral nervous system. Cases of atypical AL amyloidosis presented as spontaneous vertebral compression fractures have been rarely reported, and data about the management and clinical outcomes of the patients are scarce. Methods: Herein, we present 3 new cases of AL amyloidosis with spontaneous vertebral compression fracture and review 13 cases retrieved from the literature. Results: Moreover, we observed overrepresentations of liver involvement and bone marrow involvement in AL amyloidosis with spontaneous vertebral compression fracture. Conclusion: We believe that better awareness of the rare clinical presentation as spontaneous vertebral compression fracture of AL amyloidosis can facilitate earlier diagnosis and earlier treatment. PMID:27603350

  10. Linear immunoglobulin A bullous dermatosis.

    PubMed

    Fortuna, Giulio; Marinkovich, M Peter

    2012-01-01

    Linear immunoglobulin A (IgA) bullous dermatosis, also known as linear IgA disease, is an autoimmune mucocutaneous disorder characterized by subepithelial bullae, with IgA autoantibodies directed against several different antigens in the basement membrane zone. Its immunopathologic characteristic resides in the presence of a continuous linear IgA deposit along the basement membrane zone, which is clearly visible on direct immunofluorescence. This disorder shows different clinical features and distribution when adult-onset of linear IgA disease is compared with childhood-onset. Diagnosis is achieved via clinical, histopathologic, and immunopathologic examinations. Two common therapies are dapsone and sulfapyridine, which reduce the inflammatory response and achieve disease remission in a variable period of time.

  11. HPLC chromatofocusing of human immunoglobulins.

    PubMed

    Waldrep, J C; Schulte, J R

    1989-03-31

    A method is described for fractionation and analysis of IgA, IgM, and IgG and antibodies in human serum and/or plasma using a combination of HPLC chromatofocusing and immunoassay. A pH 9.0-3.2 gradient is utilized to separate the major proteins in the complex biological samples and monoclonal antibody based ELISAs used to determine the isotype profiles. Antigen-specific ELISAs are subsequently utilized to determine the distribution of antibody species within the chromatofocused specimens. This method is versatile since multiple simultaneous assays can easily be run on each fraction generating extensive qualitative information regarding immunoglobulin classes, subclasses, and antibodies and their distribution profiles. Such spectra will prove useful for experimental kinetic analysis of the humoral immune status of humans and experimental animals.

  12. Perspectives on Immunoglobulins in Colostrum and Milk

    PubMed Central

    Hurley, Walter L.; Theil, Peter K.

    2011-01-01

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

  13. Intestinal immunoglobulins in children with coeliac disease

    PubMed Central

    Savilahti, E.

    1972-01-01

    The numbers of immunoglobulin-containing cells in jejunal biopsy specimens of 19 children with active coeliac disease aged 0·5 to 16·5 years were studied by direct immunofluorescence. Intestinal juice immunoglobulins were measured in 14 of these patients. The number of IgA-containing cells was twice and the number of IgM-containing cells 2·5 times that of age-matched controls. There were also more IgG-, IgE-, and IgD-containing cells in the jejunal mucosa of the coeliac patients, but the absolute numbers of these cells were low. The immunoglobulin content of the intestinal juice was not altered in coeliacs. A follow-up biopsy specimen was available from seven patients kept on a strict gluten-free diet for one to four months. A significant fall in the numbers of immunoglobulin-containing cells was seen, and they did not differ at that time from the controls. Two patients were followed until full normalization of the jejunal structure and they had normal numbers of immunoglobulin-containing cells. In children with coeliac disease in contrast to adult coeliacs, the study shows that the IgA-producing system is quantitatively stimulated during gluten challenge. The rapid drop in the numbers of immunoglobulin-containing cells after gluten withdrawal suggests that there is no quantitative abnormality in the local immunoglobulin-producing system of the gut in coeliac disease. ImagesFig. 3 PMID:4568803

  14. Subcutaneous immunoglobulin in treating inflammatory neuromuscular disorders

    PubMed Central

    Yoon, Min-Suk; Gold, Ralf

    2015-01-01

    Objective: Intravenous immunoglobulin administration has long been used in the treatment of autoimmune neuromuscular disorders. Immunoglobulins may be administered by intramuscular, intravenous or subcutaneous routes. Methods: This is a report on the long-term clinical follow up of six patients with inflammatory neuromuscular disorders, that is, three chronic inflammatory demyelinating polyneuropathy (CIDP), one multifocal motor neuropathy (MMN), one inclusion body myositis (IBM) and one myasthenia gravis (MG), treated with subcutaneous immunoglobulins for a mean of 3.25 years. Results: One MMN and two CIDP patients received a weekly dose of subcutaneous immunoglobulins equivalent to intravenous immunoglobulin. One CIDP patient received a 50% dose reduction, the IBM patient received a 30% reduction and the MG patient a 20% reduction. The lower dose chosen in the majority of patients was based not only on clinical effects, but also on studies of primary immunodeficiency syndromes. One patient with CIDP showed clinical fluctuation, which was successfully treated with an adaptation of the dose of subcutaneous immunoglobulins, while the remaining patients with neuromuscular disorders had a stable clinical course for 2 years. No serious side effects were observed. Conclusions: Our results suggest that subcutaneous immunoglobulins can be an attractive alternative therapy in autoimmune neuromuscular disorders. PMID:26136842

  15. Immunoglobulin Replacement Therapy for Primary Immunodeficiency.

    PubMed

    Sriaroon, Panida; Ballow, Mark

    2015-11-01

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

  16. Formation of J-Aggregates of an Anionic Oxacarbocyanine Dye Upon Interaction with Proteins and Polyelectrolytes

    NASA Astrophysics Data System (ADS)

    Pronkin, P. G.; Tatikolov, A. S.

    2017-05-01

    J-aggregation of the anionic oxacarbocyanine dye 3,3'-di-(γ-sulfopropyl)-5,5'-diphenyl-9-ethyloxacarbocyanine betaine was studied in aqueous solutions in the presence of proteins (collagens, immunoglobulin G, serum albumins) and polyelectrolytes (polyethyleneimine, polyvinylpyrrolidone). It was found that denaturation of human serum albumin by urea stimulated J-aggregation of the dye. The dye formed two types of J-aggregates in the presence of denatured albumin and polyethyleneimine. J-aggregates formed in the presence of polyethyleneimine rearranged over time.

  17. 7th International Immunoglobulin Conference: Poster presentations.

    PubMed

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

    2014-12-01

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

  18. Thermodynamic stability contributes to immunoglobulin specificity.

    PubMed

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

    2014-05-01

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

  19. Structure and Function of Immunoglobulins

    PubMed Central

    Schroeder, Harry W; Cavacini, Lisa

    2013-01-01

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

  20. Structure and function of immunoglobulins.

    PubMed

    Schroeder, Harry W; Cavacini, Lisa

    2010-02-01

    Immunoglobulins are heterodimeric proteins composed of 2 heavy and 2 light chains. They can be separated functionally into variable domains that bind antigens and constant domains that specify effector functions, such as activation of complement or binding to Fc receptors. The variable domains are created by means of a complex series of gene rearrangement events and can then be subjected to somatic hypermutation after exposure to antigen to allow affinity maturation. Each variable domain can be split into 3 regions of sequence variability termed the complementarity-determining regions (CDRs) and 4 regions of relatively constant sequence termed the framework regions. The 3 CDRs of the heavy chain are paired with the 3 CDRs of the light chain to form the antigen-binding site, as classically defined. The constant domains of the heavy chain can be switched to allow altered effector function while maintaining antigen specificity. There are 5 main classes of heavy chain constant domains. Each class defines the IgM, IgG, IgA, IgD, and IgE isotypes. IgG can be split into 4 subclasses, IgG1, IgG2, IgG3, and IgG4, each with its own biologic properties, and IgA can similarly be split into IgA1 and IgA2.

  1. Immunoglobulin treatment in primary antibody deficiency.

    PubMed

    Maarschalk-Ellerbroek, L J; Hoepelman, I M; Ellerbroek, P M

    2011-05-01

    The primary antibody deficiency syndromes are characterised by recurrent respiratory tract infections and the inability to produce effective immunoglobulin (Ig) responses. The best-known primary antibody deficiencies are common variable immunodeficiency (CVID), X-linked agammaglobulinaemia (XLA), immunoglobulin G (IgG) subclass deficiency, and selective antibody deficiency with normal immunoglobulins (SADNI). Therapy in these patients consists of prophylactic antibiotics and/or Ig replacement therapy. Diagnostic delay remains common owing to limited awareness of the presenting features and may result in increased morbidity and mortality. Replacement therapy with immunoglobulins increases life expectancy and reduces the frequency and severity of infections, but the effect on end-organ damage is still unknown. Both intravenous immunoglobulin (IVIg) and subcutaneous immunoglobulin (SCIg) treatment appear to be safe, with comparable efficacy. A starting dose of 300-400 mg/kg/month in IVIg and 100 mg/week for SCIg is recommended. IgG trough levels should be >5 g/L for patients with agammaglobulinaemia and 3 g/L greater than the initial IgG level for patients with CVID; however, the clinical response should be foremost in choosing the dose and trough level. Infusion-related adverse reactions are generally mild owing to improved manufacturing processes. In this paper, aspects of Ig replacement therapy in primary antibody-deficient patients will be addressed. Copyright © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  2. Molecular cloning and expression of rat prostaglandin E receptor EP2 subtype.

    PubMed

    Sando, T; Usui, T; Tanaka, I; Mori, K; Sasaki, Y; Fukuda, Y; Namba, T; Sugimoto, Y; Ichikawa, A; Narumiya, S

    1994-05-16

    A cDNA clone encoding the rat prostaglandin (PG) E receptor EP2 subtype was cloned from a rat lung cDNA library. It encodes 488 amino acid residues with putative seven-transmembrane domains. Specific binding of [3H]PGE2 was found in COS-7 cells transfected with the cDNA and was displaced with unlabeled prostaglandins in the order of PGE2 = PGE1 > iloprost > or = PGF2 alpha > or = PGD2. The binding was also inhibited by misoprostol, an EP2 and EP3 agonist, but not by sulprostone, an EP1 and EP3 agonist. Northern blot analysis demonstrated that the EP2 mRNA is widely expressed in various tissues, the significant expression being observed in the thymus, lung, spleen, heart stomach, and pancreas.

  3. A Topographical Atlas of Shiga Toxin 2e Receptor Distribution in the Tissues of Weaned Piglets.

    PubMed

    Steil, Daniel; Bonse, Robert; Meisen, Iris; Pohlentz, Gottfried; Vallejo, German; Karch, Helge; Müthing, Johannes

    2016-11-30

    Shiga toxin (Stx) 2e of Stx-producing Escherichia coli (STEC) is the primary virulence factor in the development of pig edema disease shortly after weaning. Stx2e binds to the globo-series glycosphingolipids (GSLs) globotriaosylceramide (Gb3Cer, Galα1-4Galβ1-4Glcβ1-1Cer) and globotetraosylceramide (Gb4Cer, GalNAcβ1-3Galα1-4Galβ1-4Glcβ1-1Cer), the latter acting as the preferential Stx2e receptor. We determined Stx receptor profiles of 25 different tissues of a male and a female weaned piglet using immunochemical solid phase binding assays combined with mass spectrometry. All probed tissues harbored GSL receptors, ranging from high (category I) over moderate (category II) to low content (category III). Examples of Gb4Cer expression in category I tissues are small intestinal ileum, kidney pelvis and whole blood, followed by colon, small intestinal duodenum and jejunum belonging to category II, and kidney cortex, cerebrum and cerebellum as members of category III organs holding true for both genders. Dominant Gb3Cer and Gb4Cer lipoforms were those with ceramides carrying constant sphingosine (d18:1) and a variable C16:0, C22:0 or C24:1/C24:0 fatty acid. From the mapping data, we created a topographical atlas for Stx2e receptors in piglet tissues and organs, which might be helpful to further investigations on the molecular and cellular mechanisms that underlie infections of Stx2e-producing STEC in pigs and their zoonotic potential for humans.

  4. A Topographical Atlas of Shiga Toxin 2e Receptor Distribution in the Tissues of Weaned Piglets

    PubMed Central

    Steil, Daniel; Bonse, Robert; Meisen, Iris; Pohlentz, Gottfried; Vallejo, German; Karch, Helge; Müthing, Johannes

    2016-01-01

    Shiga toxin (Stx) 2e of Stx-producing Escherichia coli (STEC) is the primary virulence factor in the development of pig edema disease shortly after weaning. Stx2e binds to the globo-series glycosphingolipids (GSLs) globotriaosylceramide (Gb3Cer, Galα1-4Galβ1-4Glcβ1-1Cer) and globotetraosylceramide (Gb4Cer, GalNAcβ1-3Galα1-4Galβ1-4Glcβ1-1Cer), the latter acting as the preferential Stx2e receptor. We determined Stx receptor profiles of 25 different tissues of a male and a female weaned piglet using immunochemical solid phase binding assays combined with mass spectrometry. All probed tissues harbored GSL receptors, ranging from high (category I) over moderate (category II) to low content (category III). Examples of Gb4Cer expression in category I tissues are small intestinal ileum, kidney pelvis and whole blood, followed by colon, small intestinal duodenum and jejunum belonging to category II, and kidney cortex, cerebrum and cerebellum as members of category III organs holding true for both genders. Dominant Gb3Cer and Gb4Cer lipoforms were those with ceramides carrying constant sphingosine (d18:1) and a variable C16:0, C22:0 or C24:1/C24:0 fatty acid. From the mapping data, we created a topographical atlas for Stx2e receptors in piglet tissues and organs, which might be helpful to further investigations on the molecular and cellular mechanisms that underlie infections of Stx2e-producing STEC in pigs and their zoonotic potential for humans. PMID:27916888

  5. The Ly49E Receptor Inhibits the Immune Control of Acute Trypanosoma cruzi Infection

    PubMed Central

    Filtjens, Jessica; Coltel, Nicolas; Cencig, Sabrina; Taveirne, Sylvie; Van Ammel, Els; Van Acker, Aline; Kerre, Tessa; Matthys, Patrick; Taghon, Tom; Vandekerckhove, Bart; Carlier, Yves; Truyens, Carine; Leclercq, Georges

    2016-01-01

    The protozoan parasite Trypanosoma cruzi circulates in the blood upon infection and invades various cells. Parasites intensively multiply during the acute phase of infection and persist lifelong at low levels in tissues and blood during the chronic phase. Natural killer (NK) and NKT cells play an important role in the immune control of T. cruzi infection, mainly by releasing the cytokine IFN-γ that activates the microbicidal action of macrophages and other cells and shapes a protective type 1 immune response. The mechanisms by which immune cells are regulated to produce IFN-γ during T. cruzi infection are still incompletely understood. Here, we show that urokinase plasminogen activator (uPA) is induced early upon T. cruzi infection and remains elevated until day 20 post-infection. We previously demonstrated that the inhibitory receptor Ly49E, which is expressed, among others, on NK and NKT cells, is triggered by uPA. Therefore, we compared wild type (WT) to Ly49E knockout (KO) mice for their control of experimental T. cruzi infection. Our results show that young, i.e., 4- and 6-week-old, Ly49E KO mice control the infection better than WT mice, indicated by a lower parasite load and less cachexia. The beneficial effect of Ly49E depletion is more obvious in 4-week-old male than in female mice and weakens in 8-week-old mice. In young mice, the lower T. cruzi parasitemia in Ly49E KO mice is paralleled by higher IFN-γ production compared to their WT controls. Our data indicate that Ly49E receptor expression inhibits the immune control of T. cruzi infection. This is the first demonstration that the inhibitory Ly49E receptor can interfere with the immune response to a pathogen in vivo. PMID:27891126

  6. Thermodynamics of Protein Aggregation

    NASA Astrophysics Data System (ADS)

    Osborne, Kenneth L.; Barz, Bogdan; Bachmann, Michael; Strodel, Birgit

    Amyloid protein aggregation characterizes many neurodegenerative disorders, including Alzheimer's, Parkinson's, and Creutz- feldt-Jakob disease. Evidence suggests that amyloid aggregates may share similar aggregation pathways, implying simulation of full-length amyloid proteins is not necessary for understanding amyloid formation. In this study we simulate GNNQQNY, the N-terminal prion-determining domain of the yeast protein Sup35 to investigate the thermodynamics of structural transitions during aggregation. We use a coarse-grained model with replica-exchange molecular dynamics to investigate the association of 3-, 6-, and 12-chain GNNQQNY systems and we determine the aggregation pathway by studying aggregation states of GN- NQQNY. We find that the aggregation of the hydrophilic GNNQQNY sequence is mainly driven by H-bond formation, leading to the formation of /3-sheets from the very beginning of the assembly process. Condensation (aggregation) and ordering take place simultaneously, which is underpinned by the occurrence of a single heat capacity peak only.

  7. 6th International Immunoglobulin Symposium: poster presentations.

    PubMed

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

    2009-12-01

    The posters presented at the 6th International Immunoglobulin Symposium covered a wide range of fields and included both basic science and clinical research. From the abstracts accepted for poster presentation, 12 abstracts were selected for oral presentations in three parallel sessions on immunodeficiencies, autoimmunity and basic research. The immunodeficiency presentations dealt with novel, rare class-switch recombination (CSR) deficiencies, attenuation of adverse events following IVIg treatment, association of immunoglobulin (Ig)G trough levels and protection against acute infection in patients with X-linked agammaglobulinaemia (XLA) and common variable immunodeficiency (CVID), and the reduction of class-switched memory B cells in patients with specific antibody deficiency (SAD). The impact of intravenous immunoglobulin on fetal alloimmune thrombocytopenia, pregnancy and postpartum-related relapses in multiple sclerosis and refractory myositis, as well as experiences with subcutaneous immunoglobulin in patients with multi-focal motor neuropathy, were the topics presented in the autoimmunity session. The interaction of dendritic cell (DC)-SIGN and alpha2,6-sialylated IgG Fc and its impact on human DCs, the enrichment of sialylated IgG in plasma-derived IgG, as wells as prion surveillance and monitoring of anti-measles titres in immunoglobulin products, were covered in the basic science session. In summary, the presentations illustrated the breadth of immunoglobulin therapy usage and highlighted the progress that is being made in diverse areas of basic and clinical research, extending our understanding of the mechanisms of immunoglobulin action and contributing to improved patient care.

  8. Secretory immunoglobulin A and immunoglobulin G in horse saliva.

    PubMed

    Palm, Anna-Karin E; Wattle, Ove; Lundström, Torbjörn; Wattrang, Eva

    2016-11-01

    This study aimed to increase the knowledge on salivary antibodies in the horse since these constitute an important part of the immune defence of the oral cavity. For that purpose assays to detect horse immunoglobulin A (IgA) including secretory IgA (SIgA) were set up and the molecular weights of different components of the horse IgA system were estimated. Moreover, samples from 51 clinically healthy horses were tested for total SIgA and IgG amounts in saliva and relative IgG3/5 (IgG(T)) and IgG4/7 (IgGb) content were tested in serum and saliva. Results showed a mean concentration of 74μg SIgA/ml horse saliva and that there was a large inter-individual variation in salivary SIgA concentration. For total IgG the mean concentration was approx. 5 times lower than that of SIgA, i.e. 20μg IgG/ml saliva and the inter-individual variation was lower than that observed for SIgA. The saliva-serum ratio for IgG isotypes IgG3/5 and IgG4/7 was also assessed in the sampled horses and this analysis showed that the saliva-serum ratio of IgG4/7 was in general approximately 4 times higher than that of IgG3/5. The large inter-individual variation in salivary SIgA levels observed for the normal healthy horses in the present study emphasises the need for a large number of observations when studying this parameter especially in a clinical setting. Moreover, our results also indicated that some of the salivary IgG does not originate from serum but may be produced locally. Thus, these results provide novel insight, and a base for further research, into salivary antibody responses of horses.

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

    PubMed

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

    2014-04-01

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

  10. On mean type aggregation.

    PubMed

    Yager, R R

    1996-01-01

    We introduce and define the concept of mean aggregation of a collection of n numbers. We point out that the lack of associativity of this operation compounds the problem of the extending mean of n numbers to n+1 numbers. The closely related concepts of self identity and the centering property are introduced as one imperative for extending mean aggregation operators. The problem of weighted mean aggregation is studied. A new concept of prioritized mean aggregation is then introduced. We next show that the technique of selecting an element based upon the performance of a random experiment can be considered as a mean aggregation operation.

  11. IgG Conformer's Binding to Amyloidogenic Aggregates

    PubMed Central

    Phay, Monichan; Welzel, Alfred T.; Williams, Angela D.; McWilliams-Koeppen, Helen P.; Blinder, Veronika; O'Malley, Tiernan T.; Solomon, Alan; Walsh, Dominic M.; O'Nuallain, Brian

    2015-01-01

    Amyloid-reactive IgGs isolated from pooled blood of normal individuals (pAbs) have demonstrated clinical utility for amyloid diseases by in vivo targeting and clearing amyloidogenic proteins and peptides. We now report the following three novel findings on pAb conformer's binding to amyloidogenic aggregates: 1) pAb aggregates have greater activity than monomers (HMW species > dimers > monomers), 2) pAbs interactions with amyloidogenic aggregates at least partially involves unconventional (non-CDR) interactions of F(ab) regions, and 3) pAb's activity can be easily modulated by trace aggregates generated during sample processing. Specifically, we show that HMW aggregates and dimeric pAbs present in commercial preparations of pAbs, intravenous immunoglobulin (IVIg), had up to ~200- and ~7-fold stronger binding to aggregates of Aβ and transthyretin (TTR) than the monomeric antibody. Notably, HMW aggregates were primarily responsible for the enhanced anti-amyloid activities of Aβ- and Cibacron blue-isolated IVIg IgGs. Human pAb conformer's binding to amyloidogenic aggregates was retained in normal human sera, and mimicked by murine pAbs isolated from normal pooled plasmas. An unconventional (non-CDR) component to pAb's activity was indicated from control human mAbs, generated against non-amyloid targets, binding to aggregated Aβ and TTR. Similar to pAbs, HMW and dimeric mAb conformers bound stronger than their monomeric forms to amyloidogenic aggregates. However, mAbs had lower maximum binding signals, indicating that pAbs were required to saturate a diverse collection of binding sites. Taken together, our findings strongly support further investigations on the physiological function and clinical utility of the inherent anti-amyloid activities of monomeric but not aggregated IgGs. PMID:26367058

  12. Immunoglobulin classes of Aleutian disease virus antibody.

    PubMed Central

    Porter, D D; Porter, H G; Suffin, S C; Larsen, A E

    1984-01-01

    Aleutian disease virus (ADV) persistently infects mink and causes marked hypergammaglobulinemia. Immunoglobulin class-specific antisera were used to define the total immunoglobulin of each class by radial immunodiffusion and the immunoglobulin class of ADV-specific antibody by immunofluorescence in experimentally and naturally infected mink. Electrophoretic gamma globulin closely reflects the immunoglobulin G (IgG) level in mink, and the majority of the increased immunoglobulin and ADV antibody in infected mink is IgG. IgM becomes elevated within 6 days after infection, reaches peak levels by 15 to 18 days, and returns to normal by 60 days after infection. The first ADV antibody demonstrable is IgM, and most mink have virus-specific IgM antibody for at least 85 days postinfection. Serum IgA levels in normal mink are not normally distributed, and ADV infection causes a marked elevation of IgA. Low levels of ADV-specific IgA antibody can be shown throughout the course of infection. Failure of large amounts of virus-specific IgG antibody to inhibit the reaction of virus-specific IgM and IgA antibodies suggests that the various classes of antibodies are directed against spatially different antigenic determinants. The IgM and IgA were shown not to be rheumatoid factors. PMID:6319283

  13. Immunoglobulin isotypes in childhood asthma.

    PubMed

    Najam, F I; Giasuddin, A S; Shembesh, A H

    1999-01-01

    Immunoglobulin isotypes (IgG, IgA, IgM, IgD, IgE) in serum were investigated in 64 Libyan children with mild to moderately severe asthma (age: 1-12 years; sex: 39 males, 25 females) (Group A) and in 57 healthy Libyan children (age: 1-12 years; sex: 30 males, 27 females (Group B). The patients were classified according to age into three groups (A1: 1-3 years; A2: > 3-5 years; A3: > 5-12 years); according to disease activity into two groups (AA: active disease; NA: inactive disease); and according to age plus disease activity into six groups (AA1, NA1; AA2, NA2; AA3, NA3). The healthy children were also divided according to age into three groups (B1: 1-3 years; B2: > 3-5 years; B3: > 5-12 years). IgG, IgA, IgM and IgD were measured by radial immunodiffusion method and IgE was estimated by enzyme immunoassay technique utilizing immunokits from bioMerieux, France. Serum levels of IgG, IgD and IgE were elevated significantly in patients compared to controls (A vs B: p < 0.05) while IgA and IgM levels were normal (p > 0.05). IgG and IgD levels were raised in A3 (p < 0.05), while IgD levels were raised in both A2 and A3 (p < 0.05) and IgE was elevated in all age groups (p < 0.05). However, IgG was elevated significantly in AA only, while IgD and IgE levels were high in both AA and NA (p < 0.05) and IgE was even considerably higher in AA compared to NA (p < 0.02). Further elevated levels were observed for IgG in AA3 only (p < 0.05), for IgD in NA2 (p < 0.01), AA3 (p < 0.01) and NA3 (p < 0.05) and IgE was much higher in patients with active disease than with inactive disease in all age groups (p < 0.05). The fact that asthmatic attack in majority of our patients can be explained as mediated through IgE and the possibilities that IgG and IgD may play roles as aetiopathogenetic or protective regulatory factors in childhood asthma are discussed.

  14. IMMUNOGLOBULIN PATTERNS IN SCHIZOPHRENIC PATIENTS1

    PubMed Central

    Tiwari, S.G.; Lal, Narottam; Trivedi, J.K.; Sayeed, J.; Bahauguna, L.M.

    1984-01-01

    SUMMARY Immunoglobulins G, M and A were estimated in serum and cerebrospinal fluid (CSF) of 30 schizophrenics, 20 neurological controls and 20 surgical controls. Significant increased levels of serum Ig A and M were detected in schizophrenics. An association was observed between increasing levels of serum IgA and IgM with the duration of disease and the number of episodes. CSF IgG/TP% was also significantly increased with the severity of the disease. On the basis of viral aetiology of schizophrenia it can be concluded that the increase in immunoglobulins synthesis might be due to the persistent antigenic stimulation. PMID:21965989

  15. Estimation of bovine colostral immunoglobulins by refractometry.

    PubMed

    Molla, A

    1980-07-12

    The total protein of colostral whey from dairy cows as determined by a refractometer were compared with the immune globulin concentration obtained by cellulose acetate membrane electrophoresis and the immunoglobulin (IgA + IgG + IgM) contents determined by radial immunodiffusion. The coefficient of correlation between the results obtained by refractometry and electrophoresis was 0.98 (P < 0.001). The correlation between refractometry and radial immunodiffusion was 0.89 (P < 0.001), while that of electrophoresis and radial immunodiffusion was 0.87 (P < 0.001). Refractometry can be used as a simple, fast and inexpensive indirect method of assessing immunoglobulins in colostral whey.

  16. Switch Transcripts in Immunoglobulin Class Switching

    NASA Astrophysics Data System (ADS)

    Lorenz, Matthias; Jung, Steffen; Radbruch, Andreas

    1995-03-01

    B cells can exchange gene segments for the constant region of the immunoglobulin heavy chain, altering the class and effector function of the antibodies that they produce. Class switching is directed to distinct classes by cytokines, which induce transcription of the targeted DNA sequences. These transcripts are processed, resulting in spliced "switch" transcripts. Switch recombination can be directed to immunoglobulin G1 (IgG1) by the heterologous human metallothionein II_A promoter in mutant mice. Induction of the structurally conserved, spliced switch transcripts is sufficient to target switch recombination to IgG1, whereas transcription alone is not.

  17. Cellular myeloperoxidase activity in human monocytes stimulated by hyposialylated immunoglobulins and rheumatoid factors.

    PubMed Central

    Dodon, M D; Gazzolo, L; Quash, G A

    1984-01-01

    When hyposialylated , immunoglobulins become immunogenic and tend to form aggregates. In pursuit of the possibility that hyposialylated immunoglobulins (hs-Ig) can trigger human mononuclear phagocytic cells, we have investigated the effects of such hs-Ig on the myeloperoxidase (MPO) activity of these cells. The incubation of human monocytes with aggregated hs-Ig leads to the decrease of intracellular MPO activity. This decrease is dependent on the incubation time, on the amount of hs-Ig added, and on the degree of aggregation. Incubation with unaggregated hs-Ig has a similar effect, thus providing evidence that the loss of sialic acid residues per se is enough to render these molecules capable of decreasing the MPO content of phagocytic cells. Furthermore, human rheumatoid factors, isolated from the sera of rheumatoid arthritis patients, and previously characterized as hyposailylated Ig, interact in the same way with monocytes in triggering the MPO decrease. These observations imply that hs-Ig may be considered as active stimuli in the induction of inflammatory processes, through the initiation of oxidative reactions. PMID:6329948

  18. O6.09PROSTAGLANDIN E RECEPTOR-4 ACTIVATION REGULATES TRYPTOPHAN METABOLISM IN HUMAN MALIGNANT GLIOMAS

    PubMed Central

    Ochs, K.; Ott, M.; Rauschenbach, K.J.; Sahm, F.; Opitz, C.A.; von Deimling, A.; Wick, W.; Platten, M.

    2014-01-01

    Malignant gliomas generate a local immunosuppressive microenvironment as well as systemic immunosuppression. Tryptophan-2,3-dioxygenase (TDO)-mediated tryptophan metabolism and the production of immunosuppressive prostaglandins relevantly contribute to this inhibition of anti-glioma immune responses. We now connect these two critical immunosuppressive pathways by demonstrating that prostaglandins enhance TDO expression and enzymatic activity in malignant gliomas via activation of prostaglandin E receptor-4 (EP4). Stimulation with prostaglandin E2 (PGE2) concentration-dependently upregulates TDO-mediated kynurenine release in human glioma cell lines, while knockdown of the PGE2 receptor EP4 inhibits TDO expression and activity. In tissue of human malignant gliomas expression of the PGE2-producing enzyme cyclooxygenase-2 (COX-2) and its receptor EP4 are associated with TDO expression both on transcript and protein level. Of clinical relevance, high expression of EP4 correlates with poor survival in patients with gliomas of the WHO grades III and IV. Importantly, treatment of glioma cells with an EP4 inhibitor decreased TDO expression and activity. In summary targeting EP4 may inhibit both immunosuppressive COX-2 signaling as well as tryptophan degradation and thus could provide a novel immunotherapeutic avenue for the treatment of malignant gliomas.

  19. IgE Receptor-Mediated Mast-Cell Renin Release

    PubMed Central

    Aldi, Silvia; Robador, Pablo A.; Tomita, Kengo; Di Lorenzo, Annarita; Levi, Roberto

    2015-01-01

    Renin is a newly discovered constituent of mast cells. Given that mast cells play a major role in IgE-mediated allergic hypersensitivity, we investigated whether activation of the high-affinity IgE receptor FcεRI elicits release of mast-cell renin. Cross-linking of FcεRI on the surface of mature bone marrow–derived mast cells elicited release of enzymatically active renin protein. The angiotensin I–forming activity of the renin protein was completely blocked by the selective renin inhibitor BILA 2157, which excludes formation of angiotensin I by proteases other than renin. FcεRI-mediated mast-cell renin release was inhibited by dexamethasone and potentiated by the proinflammatory mediator PGE2. Furthermore, cross-linking of mast-cell FcεRI in ex vivo murine hearts passively sensitized with monoclonal anti-DNP IgE also resulted in mast-cell degranulation and overflow of renin. Our findings indicate that IgE-mediated allergic hypersensitivity provokes release of renin from both cultured and resident cardiac mast cells, a process likely to be exacerbated in a chronic inflammatory background. Given the widespread distribution of mast cells, and the presence of angiotensinogen and angiotensin-converting enzyme in many tissues, renin release in immediate hypersensitivity reactions could result in local angiotensin II generation and multiorgan dysfunctions. PMID:24262755

  20. The mouse prostaglandin E receptor EP2 subtype: cloning, expression, and northern blot analysis.

    PubMed

    Katsuyama, M; Nishigaki, N; Sugimoto, Y; Morimoto, K; Negishi, M; Narumiya, S; Ichikawa, A

    1995-09-25

    A functional cDNA clone for the mouse prostaglandin (PG) E receptor EP2 subtype was isolated from a mouse cDNA library. The mouse EP2 receptor consists of 362 amino acid residues with seven putative transmembrane domains. [3H]PGE2 bound specifically to the membrane of Chinese hamster ovary cells stably expressing the cloned receptor. This binding was displaced by unlabeled prostanoids in the order of PGE2 = PGE1 > iloprost, a stable PGI2 agonist > PGF2 alpha > PGD2. Binding was also inhibited by butaprost (an EP2 agonist) and to a lesser extent by M&B 28767 (an EP3 agonist), but not by sulprostone (an EP1 and EP3 agonist) or SC-19220 (an EP1 antagonist). PGE2 and butaprost increased the cAMP level in the Chinese hamster ovary cells in a concentration-dependent manner. Northern blot analysis revealed that EP2 mRNA is expressed most abundantly in the uterus, followed by the spleen, lung, thymus, ileum, liver, and stomach.

  1. Cloning and expression of a cDNA for mouse prostaglandin E receptor EP2 subtype.

    PubMed

    Honda, A; Sugimoto, Y; Namba, T; Watabe, A; Irie, A; Negishi, M; Narumiya, S; Ichikawa, A

    1993-04-15

    A functional cDNA clone encoding mouse EP2 subtype of prostaglandin (PG) E receptor was isolated from a mouse cDNA library by cross-hybridization with the mouse EP3 subtype PGE receptor cDNA. The mouse EP2 receptor consists of 513 amino acid residues with putative seven-transmembrane domains. In contrast to EP3 receptor, this receptor possesses long third intracellular loop and carboxyl-terminal tail. [3H] PGE2 specifically bound to the membrane of mammalian COS cells transfected with the cDNA. The binding to the membrane was displaced with unlabeled PG in the order of PGE2 = PGE1 > iloprost > or = PGF2 alpha > or = PGD2. The binding was also inhibited by misoprostol, an EP2 and EP3 agonist, but not by sulprostone, an EP1 and EP3 agonist, and SC-19220, an EP1 antagonist. PGE2 markedly increased cAMP level in COS cells transfected with the cDNA. These results suggest that this receptor is EP2 subtype. Northern blot analysis demonstrated that the EP2 mRNA is widely expressed in various tissues, the abundant expression being observed in ileum, thymus, and mastocytoma P-815 cells.

  2. Immunoglobulin production by human-mouse somatic cell hybrids.

    PubMed

    Smith, M; Hirschhorn, K

    1977-01-01

    Studies on immunoglobulin production in human-mouse somatic cell hybrids suggest: 1. The structural genes for heavy chain immunoglobulins are carried on chromsome 6, probably on the short arm or the proximal half of the long arm of the chromosome. 2. The structural gene for kappa light chain immunoglobulin may be carried on chromsome 11. 3. The occurrence of immunoglobulin molecules on the cell surface requires the presence of chromosome 2.

  3. Intestinal Absorption of Immunoglobulins by Newborn Infants

    PubMed Central

    Iyengar, Leela; Selvaraj, R. J.

    1972-01-01

    Intestinal absorption in newborn infants of immunoglobulins present in colostrum was studied by measuring the concentrations of immunoglobulins IgA, IgG, and IgM in cord blood and following the changes in the serum of the infant on the 5th day after birth. In infants who did not receive colostrum, a marked fall in IgG levels was observed on the 5th day after birth as compared to levels at birth. The concentrations of IgA and IgM showed marginal changes. In contrast, colostrumfed infants showed significant increases in the concentration of IgG. Levels of all 3 immunoglobulins on the 5th day were significantly higher in the serum of colostrumfed infants as compared to those who did not receive colostrum. It is suggested that immunoglobulins present in colostrum are to some extent absorbed from the intestinal tract of newborn infants, and this may have some physiological significance in the resistance to infection during the early neonatal period. PMID:4624594

  4. Anticonvulsant hypersensitivity syndrome treated with intravenous immunoglobulin.

    PubMed

    Dredge, David C; Parsons, Elizabeth C; Carter, Lindsay P; Staley, Kevin J

    2010-07-01

    Anticonvulsant hypersensitivity syndrome is a severe, potentially life-threatening, reaction to the aromatic anticonvulsant medications. Reported here is a case of anticonvulsant hypersensitivity syndrome secondary to phenobarbital in a 2-year-old boy; he responded to drug withdrawal, corticosteroids, and intravenous immunoglobulin. The literature regarding treatment of this syndrome is reviewed.

  5. Immunoglobulins in tears of normal Indian people.

    PubMed Central

    Sen, D. K.; Sarin, G. S.; Mani, K.; Saha, K.

    1976-01-01

    Immunoglobulin concentrations in tears from 50 healthy Indians aged from 14 to 50 years were measured by a standard immunodiffusion method. The levels of IgA were substantial; those of IgG were very low; and IgD and IgM were not present. The mean IgA level was 24-6 mg/100 ml. PMID:1276121

  6. Eastern Equine Encephalitis Treated With Intravenous Immunoglobulins

    PubMed Central

    Mukerji, Shibani S.; Lam, Alice D.

    2016-01-01

    We report the case of a 68-year-old man from southeastern Massachusetts presenting with encephalitis due to eastern equine encephalitis (EEE) virus. Despite the high morbidity and mortality rate of EEE, the patient made a near complete recovery in the setting of receiving early intravenous immunoglobulins. PMID:26740855

  7. Eastern Equine Encephalitis Treated With Intravenous Immunoglobulins.

    PubMed

    Mukerji, Shibani S; Lam, Alice D; Wilson, Michael R

    2016-01-01

    We report the case of a 68-year-old man from southeastern Massachusetts presenting with encephalitis due to eastern equine encephalitis (EEE) virus. Despite the high morbidity and mortality rate of EEE, the patient made a near complete recovery in the setting of receiving early intravenous immunoglobulins.

  8. Aggregations in Flatworms.

    ERIC Educational Resources Information Center

    Liffen, C. L.; Hunter, M.

    1980-01-01

    Described is a school project to investigate aggregations in flatworms which may be influenced by light intensity, temperature, and some form of chemical stimulus released by already aggregating flatworms. Such investigations could be adopted to suit many educational levels of science laboratory activities. (DS)

  9. Aggregations in Flatworms.

    ERIC Educational Resources Information Center

    Liffen, C. L.; Hunter, M.

    1980-01-01

    Described is a school project to investigate aggregations in flatworms which may be influenced by light intensity, temperature, and some form of chemical stimulus released by already aggregating flatworms. Such investigations could be adopted to suit many educational levels of science laboratory activities. (DS)

  10. An in vivo platform for identifying inhibitors of protein aggregation

    PubMed Central

    Mahood, Rachel A.; Jackson, Matthew P.; Revill, Charlotte H.; Foster, Richard J.; Smith, D. Alastair; Ashcroft, Alison E.; Brockwell, David J.; Radford, Sheena E.

    2015-01-01

    Protein aggregation underlies an array of human diseases, yet only one small molecule therapeutic has been successfully developed to date. Here, we introduce an in vivo system, based on a β-lactamase tripartite fusion construct, capable of identifying aggregation-prone sequences in the periplasm of Escherichia coli and inhibitors that prevent their aberrant self-assembly. We demonstrate the power of the system using a range of proteins, from small unstructured peptides (islet amyloid polypeptide and amyloid β) to larger, folded immunoglobulin domains. Configured in a 48-well format, the split β-lactamase sensor readily differentiates between aggregation-prone and soluble sequences. Performing the assay in the presence of 109 compounds enabled a rank ordering of inhibition and revealed a new inhibitor of IAPP aggregation. This platform can be applied to both amyloidogenic and other aggregation-prone systems, independent of sequence or size, and can identify small molecules or other factors able to ameliorate or inhibit protein aggregation. PMID:26656088

  11. Fc Receptors for Immunoglobulins and Their Appearance during Vertebrate Evolution

    PubMed Central

    Akula, Srinivas; Mohammadamin, Sayran; Hellman, Lars

    2014-01-01

    Receptors interacting with the constant domain of immunoglobulins (Igs) have a number of important functions in vertebrates. They facilitate phagocytosis by opsonization, are key components in antibody-dependent cellular cytotoxicity as well as activating cells to release granules. In mammals, four major types of classical Fc receptors (FcRs) for IgG have been identified, one high-affinity receptor for IgE, one for both IgM and IgA, one for IgM and one for IgA. All of these receptors are related in structure and all of them, except the IgA receptor, are found in primates on chromosome 1, indicating that they originate from a common ancestor by successive gene duplications. The number of Ig isotypes has increased gradually during vertebrate evolution and this increase has likely been accompanied by a similar increase in isotype-specific receptors. To test this hypothesis we have performed a detailed bioinformatics analysis of a panel of vertebrate genomes. The first components to appear are the poly-Ig receptors (PIGRs), receptors similar to the classic FcRs in mammals, so called FcRL receptors, and the FcR γ chain. These molecules are not found in cartilagous fish and may first appear within bony fishes, indicating a major step in Fc receptor evolution at the appearance of bony fish. In contrast, the receptor for IgA is only found in placental mammals, indicating a relatively late appearance. The IgM and IgA/M receptors are first observed in the monotremes, exemplified by the platypus, indicating an appearance during early mammalian evolution. Clearly identifiable classical receptors for IgG and IgE are found only in marsupials and placental mammals, but closely related receptors are found in the platypus, indicating a second major step in Fc receptor evolution during early mammalian evolution, involving the appearance of classical IgG and IgE receptors from FcRL molecules and IgM and IgA/M receptors from PIGR. PMID:24816777

  12. Marine Synechococcus Aggregation

    NASA Astrophysics Data System (ADS)

    Neuer, S.; Deng, W.; Cruz, B. N.; Monks, L.

    2016-02-01

    Cyanobacteria are considered to play an important role in the oceanic biological carbon pump, especially in oligotrophic regions. But as single cells are too small to sink, their carbon export has to be mediated by aggregate formation and possible consumption by zooplankton producing sinking fecal pellets. Here we report results on the aggregation of the ubiquitous marine pico-cyanobacterium Synechococcus as a model organism. We first investigated the mechanism behind such aggregation by studying the potential role of transparent exopolymeric particles (TEP) and the effects of nutrient (nitrogen or phosphorus) limitation on the TEP production and aggregate formation of these pico-cyanobacteria. We further studied the aggregation and subsequent settling in roller tanks and investigated the effects of the clays kaolinite and bentonite in a series of concentrations. Our results show that despite of the lowered growth rates, Synechococcus in nutrient limited cultures had larger cell-normalized TEP production, formed a greater volume of aggregates, and resulted in higher settling velocities compared to results from replete cultures. In addition, we found that despite their small size and lack of natural ballasting minerals, Synechococcus cells could still form aggregates and sink at measureable velocities in seawater. Clay minerals increased the number and reduced the size of aggregates, and their ballasting effects increased the sinking velocity and carbon export potential of aggregates. In comparison with the Synechococcus, we will also present results of the aggregation of the pico-cyanobacterium Prochlorococcus in roller tanks. These results contribute to our understanding in the physiology of marine Synechococcus as well as their role in the ecology and biogeochemistry in oligotrophic oceans.

  13. Membrane-associated immunoglobulins of human lymphocytes in immunologic disorders

    PubMed Central

    Nicod, Isabelle; Girard, J. P.; Cruchaud, A.

    1973-01-01

    Membrane-associated immunoglobulins of peripheral blood lymphocytes were studied by indirect immunofluorescence for γ, α, μ, κ and λ chains in healthy subjects and patients with immunologic disease. In healthy subjects, heavy chains were found on 30·7% of lymphocytes (γ 15·3%, α 7·2% and μ 8·2%) and light chains on 32·8% of cells (κ 20·4% and λ 12·4%). Patients with humoral immune deficiencies had fewer immunoglobulin-bearing cells; sarcoidosis or thymectomy patients had normal or decreased immunoglobulin-bearing lymphocytes; cells with light chains were fewer than those with heavy chains on their lymphocytes. In some cases, normal levels of serum immunoglobulins were found in the absence of the corresponding immunoglobulin-bearing cells, and in others normal immunoglobulin-bearing lymphocytes were present in the absence of the corresponding serum immunoglobulins. These data suggest that (1) immunoglobulin-bearing lymphocytes in blood do not reflect the condition of immunoglobulin-synthesizing cells in peripheral lymphoid tissues, and (2) in certain immunologic disorders, either some B-lymphocytes do not synthesize immunoglobulins, or immunoglobulins are in such a situation that the whole molecule or part of the molecule is not visualized by current methods. PMID:4587505

  14. Immunoglobulin expression and synthesis by human haemic cell lines.

    PubMed Central

    Gordon, J; Hough, D; Karpas, A; Smith, J L

    1977-01-01

    Twenty-six human cell lines derived from a variety of lymphoid and non-lymphoid malignancies, were investigated for their immunological markers, with special reference to the class of immunoglobulin expressed. Twenty-five of the lines stained positively for surface immunoglobulin and IgD together with IgM proved to be the major immunoglobulin classes on these cells. Six of the lines were chosen for a study of their immunoglobulin synthesis patterns over an 18-h period and the immunoglobulin produced was analysed on SDS-polyacrylamide gel electrophoresis. Patterns obtained from the cell lines were similar to that from normal lymph node lymphocytes and differed markedly to plasma cells. Two of the cell lines had abnormal immunoglobulin synthesis patterns characterized as free light chains in one case. The cell lines are evaluated for their usefulness as models of immunoglobulin synthesis and analogues of normal and neoplastic states. PMID:608682

  15. Influence of surface and protein modification on immunoglobulin G adsorption observed by scanning force microscopy.

    PubMed Central

    Droz, E; Taborelli, M; Descouts, P; Wells, T N

    1994-01-01

    Scanning force microscopy has been used successfully to produce images of individual protein molecules. However, one of the problems with this approach has been the high mobility of the proteins caused by the interaction between the sample and the scanning tip. To stabilize the proteins we have modified the adsorption properties of immunoglobulin G on graphite and mica surfaces. We have used two approaches: first, we applied glow discharge treatment to the surface to increase the hydrophilicity, favoring adhesion of hydrophilic protein molecules; second, we used the arginine modifying reagent phenylglyoxal to increase the protein hydrophobicity and thus enhance its adherence to hydrophobic surfaces. We used scanning force microscopy to show that the glow discharge treatment favors a more homogeneous distribution and stronger adherence of the protein molecules to the graphite surface. Chemical modification of the immunoglobulin caused increased aggregation of the proteins on the surface but did not improve the adherence to graphite. On mica, clusters of modified immunoglobulins were also observed and their adsorption was reduced. These results underline the importance of the surface hydrophobicity and charge in controlling the distribution of proteins on the surface. Images FIGURE 2 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 PMID:7811946

  16. Charged Dust Aggregate Interactions

    NASA Astrophysics Data System (ADS)

    Matthews, Lorin; Hyde, Truell

    2015-11-01

    A proper understanding of the behavior of dust particle aggregates immersed in a complex plasma first requires a knowledge of the basic properties of the system. Among the most important of these are the net electrostatic charge and higher multipole moments on the dust aggregate as well as the manner in which the aggregate interacts with the local electrostatic fields. The formation of elongated, fractal-like aggregates levitating in the sheath electric field of a weakly ionized RF generated plasma discharge has recently been observed experimentally. The resulting data has shown that as aggregates approach one another, they can both accelerate and rotate. At equilibrium, aggregates are observed to levitate with regular spacing, rotating about their long axis aligned parallel to the sheath electric field. Since gas drag tends to slow any such rotation, energy must be constantly fed into the system in order to sustain it. A numerical model designed to analyze this motion provides both the electrostatic charge and higher multipole moments of the aggregate while including the forces due to thermophoresis, neutral gas drag, and the ion wakefield. This model will be used to investigate the ambient conditions leading to the observed interactions. This research is funded by NSF Grant 1414523.

  17. A Soluble Form of the High Affinity IgE Receptor, Fc-Epsilon-RI, Circulates in Human Serum

    PubMed Central

    Dehlink, Eleonora; Platzer, Barbara; Baker, Alexandra H.; LaRosa, Jessica; Pardo, Michael; Dwyer, Peter; Yen, Elizabeth H.; Szépfalusi, Zsolt

    2011-01-01

    Soluble IgE receptors are potential in vivo modulators of IgE-mediated immune responses and are thus important for our basic understanding of allergic responses. We here characterize a novel soluble version of the IgE-binding alpha-chain of Fc-epsilon-RI (sFcεRI), the high affinity receptor for IgE. sFcεRI immunoprecipitates as a protein of ∼40 kDa and contains an intact IgE-binding site. In human serum, sFcεRI is found as a soluble free IgE receptor as well as a complex with IgE. Using a newly established ELISA, we show that serum sFcεRI levels correlate with serum IgE in patients with elevated IgE. We also show that serum of individuals with normal IgE levels can be found to contain high levels of sFcεRI. After IgE-antigen-mediated crosslinking of surface FcεRI, we detect sFcεRI in the exosome-depleted, soluble fraction of cell culture supernatants. We further show that sFcεRI can block binding of IgE to FcεRI expressed at the cell surface. In summary, we here describe the alpha-chain of FcεRI as a circulating soluble IgE receptor isoform in human serum. PMID:21544204

  18. Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy.

    PubMed

    Van Schaik, I N; Winer, J B; De Haan, R; Vermeulen, M

    2002-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy is an immune mediated disorder characterised by progressive or relapsing symmetrical motor or sensory symptoms and signs in more than one limb, developing over at least two months. It may cause prolonged periods of disability and even death. Several uncontrolled studies have suggested a beneficial effect of intravenous immunoglobulin. To review systematically the evidence from randomised controlled trials concerning the efficacy and safety of intravenous immunoglobulin in chronic inflammatory demyelinating polyradiculoneuropathy. We used the Search Strategy of the Cochrane Neuromuscular Disease Review Group to search the Disease Group register and other databases for randomised controlled trials from 1985 onwards. Randomised controlled studies examining the effects of any dose of intravenous immunoglobulin versus placebo, plasma exchange or corticosteroids in patients with definite or probable chronic inflammatory demyelinating polyradiculoneuropathy. Outcome measures had to include one of the following: a disability score, the Medical Research Council sum score, electrophysiological data or walking distance. Studies which reported the frequency of adverse effects were used to assess the safety of treatment. Two reviewers independently reviewed literature searches to identify potentially relevant trials, scored their quality and extracted data independently. For dichotomous data, we calculated relative risks, and for continuous data, effect sizes (for definition see statistical analysis section) and weighted pooled effect sizes. Statistical uncertainty was expressed in 95% confidence intervals. Sensitivity analysis excluding studies with quality scores below A 0.50 and below B 0.75 was planned but not performed as all studies had quality scores above 0.75. Six randomised controlled trials were considered eligible including 170 patients. Four studies on 113 patients compared intravenous immunoglobulin against

  19. Aggregate and the environment

    USGS Publications Warehouse

    Langer, William H.; Drew, Lawrence J.; Sachs, J.S.

    2004-01-01

    This book is designed to help you understand our aggregate resources-their importance, where they come from, how they are processed for our use, the environmental concerns related to their mining and processing, how those concerns are addressed, and the policies and regulations designed to safeguard workers, neighbors, and the environment from the negative impacts of aggregate mining. We hope this understanding will help prepare you to be involved in decisions that need to be made-individually and as a society-to be good stewards of our aggregate resources and our living planet.

  20. The specific immunoglobulin in hydatid disease

    PubMed Central

    Matossian, R. M.; Kane, G. J.; Chantler, S. M.; Batty, I.; Sarhadian, H.

    1972-01-01

    The variation in the serum level of specific IgG, IgM and IgA antibodies during different stages of hydatid disease has been demonstrated by a technique of fluorescent microscopy that uses monospecific anti-human immunoglobulin conjugates and freeze-dried antigens. The technique is easy to perform and our results suggest that the test is sensitive and specific. Specific IgG antibodies are present in patients with either current or past infections. IgM antibodies, detected during periods of antigenic activity, disappear soon after removal of the cyst. In many cases IgA antibodies also disappear soon after removal of the cyst. Cross-reactions between the antigens and antibodies of hydatid disease and schistosomiasis are shown to be present mainly in the IgG immunoglobulin and only to a much smaller extent in the IgA. ImagesFIG. 1 PMID:4554745

  1. Intravenous immunoglobulin therapy for refractory recurrent pericarditis.

    PubMed

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

    2014-11-01

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

  2. Chronic idiopathic thrombocytopenia treated with immunoglobulin.

    PubMed Central

    Mori, P G; Mancuso, G; del Principe, D; Duse, M; Miniero, R; Tovo, R; Bardare, M; Carnelli, V; de Mattia, D

    1983-01-01

    Twenty five children with chronic idiopathic thrombocytopenic purpura followed from 6-96 months in 7 Italian paediatric departments were treated with high dose immunoglobulin according to a multicentre protocol. Positive responses were observed in 20 of 25 patients (80%) and negative responses in 5 of 25 (20%). On previous steroid treatment 7 of 10 positive responders were steroid resistant and 13 of 15 were steroid dependent. Within four weeks of beginning treatment 16 of 20 patients (80%) relapsed, while 4 of 20 (20%) maintained normal platelet values after 4-12 months' follow up. Statistical analysis of the platelet count on day five of treatment enabled us to divide positive responders into three groups: good, intermediate, and poor. The possible mode of action and clinical application of high dose immunoglobulin are discussed. PMID:6685997

  3. Lymphoplasmacytic hypophysitis associated with immunoglobulin G4.

    PubMed

    Khong, Peter; Enno, Alar; Darwish, Balsam

    2014-02-01

    We present the unusual case of a 33-year-old woman who presented with a 2 year history of amenorrhoea and an expanding sellar lesion. Initial MRI revealed a lesion in the pituitary fossa, thought to be a pituitary adenoma. One year later, the lesion had enlarged by 5mm, with associated enhancement of the dura of the planum sphenoidale and pituitary stalk. Histopathology revealed a lymphocytic and plasma cell inflammatory infiltrate suggestive of lymphoplasmacytic hypophysitis associated with immunoglobulin G4.

  4. Intravenous immunoglobulins: evolution of commercial IVIG preparations.

    PubMed

    Hooper, John A

    2008-11-01

    Since its first use in 1952, human immunoglobulin has been used to treat people who have inherited antibody deficiencies. This article summarizes IVIG clinical development in primary immunodeficient patients and manufacturing improvements introduced over time. Manufacturing improvements include purification procedures that have reduced the incidence of adverse events and improved clinical efficacy, as well as virus inactivation and removal steps that have increased safety from blood-borne infections. Current manufacturing procedures, IVIG production trends, and recent clinical trial results are also reviewed.

  5. [Immunoglobulins in patients with Nocardia brasiliensis actinomycetoma].

    PubMed

    Méndez-Tovar, L J; Mondragón-González, R; Manzano-Gayosso, P; López-Martínez, R; Hernández-Hernández, F; Bonifaz, A; Anides Fonseca, A; Araiza, J; Vega-López, F

    2004-01-01

    Considering that some authors have reported an increasing of some immunoglobulins in actinomycetoma patients, in this study we propose to determine differential production of IgG1, IgG2, IgG3, IgG4 and IgGM in 25 patients with actinomycetoma and 25 healthy individuals from a mycetoma endemic area. Immunoglobulins were determined by ELISA technique. To sensibilize the plates, six Nocardia brasiliensis antigens were used: a crude antigen denominated NB and five derivatives (NB2, NB4, NB6, NB8 and NB10) obtained by their isoelectric point. Results showed that all IgG subclasses were higher in the patients' sera than in control sera, with a maximal difference to IgG3 and IgG4. To the latter subclass, six antigens were highly reactives. IgM levels were similar in both groups. As it occurs in other infections, in the actinomycetoma pathogenesis probably participate the increase or deficiency of a determined immunoglobulin class, as well as the relationship between different subclasses.

  6. [BIOLOGICAL AND IMMUNOCHEMICAL PROPERTIES OF POLYREACTIVE IMMUNOGLOBULINS].

    PubMed

    Bobrovnik, S A; Demchenko, M A; Komisarenko, S V

    2015-01-01

    A previously unknown phenomenon of acquired polyreactivity for serum immunoglobulins, which were subjected either to solutions of KSCN (3.0-5.0 M), low/high pH (pH 2.2-3.0), or heating to 58-60 degrees C, was described by us in 1990 year. Much later, eleven years after that, similar data were published by others, which completely confirmed our results concerning the influence of either chaotropic ions or the drastic shift of pH on immunoglobulins polyreactive properties. Our further investigations of polyreactive serum immunoglobulins (PRIG) properties have shown that the mechanism of non-specific interaction between PRIG and antigens much differs from the mechanism of interaction between specific antibodies and corresponding antigens. Later we have shown that the increasing of PRIG reactivity could be induced in vivo, and PRIG are one of serum components for human or animal sera. Then, it could be suggested that PRIG can perform certain biological functions. Studying of PRIG's effect on the phagocytosis of microbes by peritoneal cells or the tumor growth have shown that PRIG can play a certain role in protecting the body from infections and probably can influence on the development of various pathological processes. Recently we have also found that PRIG IgG contents significantly increases in aged people. These data demonstrate that further investigations of PRIG's immunochemical properties and studying of their biological role in organism protection from various diseases is very intriguing and important.

  7. [Serum and secretory immunoglobulins in allergic diseases].

    PubMed

    Atovmian, O I; German, G P; Chernokhvostova, E V

    1985-07-01

    A total of 158 patients with pollinosis, bronchial asthma, urticaria and Quincke's edema were examined. The immunoglobulin and C3 levels in sera and the immunoglobulin and albumin levels in saliva were determined by the method of single radial immunodiffusion with the corresponding monospecific antisera. In all the groups of patients subjected to examination the presence of polyclonal hypergammaglobulinemia was detected, which was manifested by a rise in the levels of IgG, IgA and especially IgM; the level of IgD was low. A decrease in the level of C3 was detected in pollinosis patients in the absence of the exacerbation of the disease. No circulating immune complexes were detected. An essential increase in the level of IgG in saliva was revealed, which was due to the local synthesis of this immunoglobulin. In winter the level of salivary IgA in pollinosis patients was found to be essentially below normal, but at the period of exacerbation it increased twofold, probably in response to local stimulation with antigen-allergen. Patients with bronchial asthma and pollinosis were found to have a high level of free secretory component (SC); in pollinosis the level of free SC sharply increased during the stage of exacerbation, which was due to the increase of its synthesis and secretion by the epithelial cells of the mucous membranes. The importance of these data for the pathogenesis of allergic diseases are discussed.

  8. Antarctic teleost immunoglobulins: more extreme, more interesting.

    PubMed

    Coscia, Maria Rosaria; Varriale, Sonia; Giacomelli, Stefano; Oreste, Umberto

    2011-11-01

    We have investigated the immunoglobulin molecule and the genes encoding it in teleosts living in the Antarctic seas at the constant temperature of -1.86 °C. The majority of Antarctic teleosts belong to the suborder Notothenioidei (Perciformes), which includes only a few non-Antarctic species. Twenty-one Antarctic and two non-Antarctic Notothenioid species were included in our studies. We sequenced immunoglobulin light chains in two species and μ heavy chains, partially or totally, in twenty species. In the case of heavy chain, genomic DNA and the cDNA encoding the secreted and the membrane form were analyzed. From one species, Trematomus bernacchii, a spleen cDNA library was constructed to evaluate the diversity of VH gene segments. T. bernacchii IgM, purified from the serum and bile, was characterized. Homology Modelling and Molecular Dynamics were used to determine the molecular structure of T. bernacchii and Chionodraco hamatus immunoglobulin domains. This paper sums up the previous results and broadens them with the addition of unpublished data.

  9. Immunoglobulin therapy in idiopathic hypothalamic dysfunction.

    PubMed

    Huppke, Peter; Heise, Alexander; Rostasy, Kevin; Huppke, Brenda; Gärtner, Jutta

    2009-09-01

    Idiopathic hypothalamic dysfunction is a rare disorder presenting at age 3-7 years. Severe hypothalamic and brainstem dysfunction leads to death in 25% of patients. The disease is presumed to be autoimmune, or in some cases paraneoplastic. No successful treatment has been reported. Patient V. developed hyperphagia, hypersomnia, and extreme aggression at age 7 years, accompanied by episodes of hyperthermia, hypothermia, sinus bradycardia, hypernatremia, hyponatremia, persistent hyperprolactinemia, hypothyroidism, and growth-hormone deficiency. At age 9 years, a diagnosis of idiopathic hypothalamic dysfunction was rendered, and immunoglobulin therapy was commenced. Nine courses of immunoglobulins, at a dose of 2 g/kg every 4 weeks, were administered. Reproducible improvements in behavior and no further episodes of hyponatremia or hypernatremia and sinus bradycardia were evident. The endocrinologic abnormalities and poor thermoregulation remained. Administration of immunoglobulins during late stages of idiopathic hypothalamic dysfunction led to improvement in some but not all signs. Assuming an autoimmune basis for this disorder, treatment during early stages of disease should be more effective. To facilitate such early treatment, increased awareness of this disorder is necessary, to allow for early diagnosis.

  10. Protein Colloidal Aggregation Project

    NASA Technical Reports Server (NTRS)

    Oliva-Buisson, Yvette J. (Compiler)

    2014-01-01

    To investigate the pathways and kinetics of protein aggregation to allow accurate predictive modeling of the process and evaluation of potential inhibitors to prevalent diseases including cataract formation, chronic traumatic encephalopathy, Alzheimer's Disease, Parkinson's Disease and others.

  11. Propagation of Tau aggregates.

    PubMed

    Goedert, Michel; Spillantini, Maria Grazia

    2017-05-30

    Since 2009, evidence has accumulated to suggest that Tau aggregates form first in a small number of brain cells, from where they propagate to other regions, resulting in neurodegeneration and disease. Propagation of Tau aggregates is often called prion-like, which refers to the capacity of an assembled protein to induce the same abnormal conformation in a protein of the same kind, initiating a self-amplifying cascade. In addition, prion-like encompasses the release of protein aggregates from brain cells and their uptake by neighbouring cells. In mice, the intracerebral injection of Tau inclusions induced the ordered assembly of monomeric Tau, followed by its spreading to distant brain regions. Short fibrils constituted the major species of seed-competent Tau. The existence of several human Tauopathies with distinct fibril morphologies has led to the suggestion that different molecular conformers (or strains) of aggregated Tau exist.

  12. Marine aggregate dynamics

    NASA Astrophysics Data System (ADS)

    The direction and scope of the Office of Naval Research's Marine Aggregate Dynamics Accelerated Research Initiative will be the topic of an open-house style meeting February 14, 7:30-10:00 P.M. in Ballroom D of the Hyatt Regency New Orleans at the Louisiana Superdome. This meeting is scheduled during the AGU/American Society of Limnology and Oceanography Ocean Sciences Meeting February 12-16 in New Orleans.The critical focus of the ARI is the measurement and modeling of the dynamics of the biological, physical, chemical and molecular processes that drive aggregation and produce aggregates. This new ARI will provide funding in Fiscal Years 1991-1995 to identify and quantify mechanisms that determine the distribution, abundance and size spectrum of aggregated particulate matter in the ocean.

  13. Aggregation and Averaging.

    ERIC Educational Resources Information Center

    Siegel, Irving H.

    The arithmetic processes of aggregation and averaging are basic to quantitative investigations of employment, unemployment, and related concepts. In explaining these concepts, this report stresses need for accuracy and consistency in measurements, and describes tools for analyzing alternative measures. (BH)

  14. Aggregation of retail stores

    NASA Astrophysics Data System (ADS)

    Jensen, Pablo; Boisson, Jean; Larralde, Hernán

    2005-06-01

    We propose a simple model to understand the economic factors that induce aggregation of some businesses over small geographical regions. The model incorporates price competition with neighboring stores, transportation costs and the satisfaction probability of finding the desired product. We show that aggregation is more likely for stores selling expensive products and/or stores carrying only a fraction of the business variety. We illustrate our model with empirical data collected in the city of Lyon.

  15. Protein aggregation and prionopathies.

    PubMed

    Renner, M; Melki, R

    2014-06-01

    Prion protein and prion-like proteins share a number of characteristics. From the molecular point of view, they are constitutive proteins that aggregate following conformational changes into insoluble particles. These particles escape the cellular clearance machinery and amplify by recruiting the soluble for of their constituting proteins. The resulting protein aggregates are responsible for a number of neurodegenerative diseases such as Creutzfeldt-Jacob, Alzheimer, Parkinson and Huntington diseases. In addition, there are increasing evidences supporting the inter-cellular trafficking of these aggregates, meaning that they are "transmissible" between cells. There are also evidences that brain homogenates from individuals developing Alzheimer and Parkinson diseases propagate the disease in recipient model animals in a manner similar to brain extracts of patients developing Creutzfeldt-Jacob's disease. Thus, the propagation of protein aggregates from cell to cell may be a generic phenomenon that contributes to the evolution of neurodegenerative diseases, which has important consequences on human health issues. Moreover, although the distribution of protein aggregates is characteristic for each disease, new evidences indicate the possibility of overlaps and crosstalk between the different disorders. Despite the increasing evidences that support prion or prion-like propagation of protein aggregates, there are many unanswered questions regarding the mechanisms of toxicity and this is a field of intensive research nowadays. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  16. Elevated autoantibody content in rheumatoid arthritis synovia with lymphoid aggregates and the effect of rituximab.

    PubMed

    Rosengren, Sanna; Wei, Nathan; Kalunian, Kenneth C; Zvaifler, Nathan J; Kavanaugh, Arthur; Boyle, David L

    2008-01-01

    The purpose of this study was to quantitatively evaluate the contribution of synovial lymphoid aggregates to autoantibody (rheumatoid factor [RF] and anti-cyclic citrullinated peptide [anti-CCP]) and total immunoglobulin (IgG and IgM) production in rheumatoid arthritis (RA) patients and the effect thereon of the B-cell-depleting antibody, rituximab, in the ARISE (Assessment of Rituximab's Immunomodulatory Synovial Effects) trial. Autoantibodies as well as total IgM and IgG were quantified by enzyme-linked immunosorbent assay in extracts of synovial tissues and matched serum from patients with RA or osteoarthritis (OA). Synovial biopsies and serum were obtained at baseline and 8 weeks following rituximab therapy in 14 RA patients. A synovial/serum index (SSI) was calculated as the ratio of synovial to serum antibody/albumin, with values above 1 representing synovial enrichment. Lymphoid aggregates were evaluated histologically. Anti-CCP IgG, but not RF-IgM, was significantly enriched in RA synovia compared with serum. Total IgM and IgG were also enriched in RA, but not in OA. SSI correlated significantly with mRNA content for both IgM and IgG, demonstrating that it reflected synovial immunoglobulin production. RA synovia with lymphocyte aggregates contained significantly elevated RF-IgM and anti-CCP IgG compared with tissues with diffuse lymphoid infiltration. Rituximab treatment did not affect synovial autoantibody or total immunoglobulin SSI overall. However, in aggregate-containing tissues, rituximab significantly reduced total IgM and IgG SSI as well as IgM and IgG1 mRNA. Surprisingly, RF-IgM and anti-CCP IgG SSIs were unchanged by rituximab in aggregate-containing synovia. Combined with earlier observations that synovial lymphoid aggregates are unaltered by rituximab treatment, these data suggest that lymphoid aggregates may provide a protective niche for autoantibody-producing cells.

  17. [Completion pneumonectomy for pulmonary aspergillosis with hyper immunoglobulin-E syndrome].

    PubMed

    Arai, H; Rino, Y; Nishii, T; Andou, K; Kurosawa, R; Kuroki, F; Imagawa, T; Mori, M; Yokota, S; Oshiro, H; Takanashi, Y

    2006-03-01

    A 22-year-old man was admitted to the department of pediatrics of our institute in February 2005, because of pulmonary aspergillosis. He had been diagnosed as hyper immunoglobulin-E syndrome in infancy, and repeated pulmonary infectious desease, such as pulmonary aspergillosis. He received art of right upper lobectomy by pulmonary aspergillosis at the age of 17. In February 2005, he had hemosputum and the chest X-ray showed a giant cavity with niveau in the right lung. In spite of medical treatment by antibiotics and antimycotics, the lesion rapidly increased in size. Therefore, right completion pneumonectomy and omentopexy around the bronchial stump was done. His postoperative course was uneventful.

  18. Symptomatic Primary Selective Immunoglobulin M Deficiency with Nonprotective Pneumococcal Titers Responsive to Subcutaneous Immunoglobulin Treatment.

    PubMed

    Patel, Shiven S; Fergeson, Jennifer E; Glaum, Mark C; Lockey, Richard F

    2016-01-01

    Selective immunoglobulin M deficiency (SIgMD) is a rare disorder with varying clinical features. The prevalence of SIgMD is 0.03-3%. Patients may be asymptomatic or else present with recurrent infection, autoimmunity, atopic disease and/or malignancy. About 50% of patients with symptomatic SIgMD also have impaired antibody responses to the pneumococcal polysaccharide vaccine. We report on an adult who presented with symptomatic SIgMD with impaired pneumococcal polysaccharide antibody responses and lymphopenia, who experienced a significant clinical improvement in the frequency of infections after subcutaneous immunoglobulin replacement therapy.

  19. Immunoglobulin patterns in humans over 95 years of age.

    PubMed Central

    Radl, J; Sepers, J M; Skvaril, F; Morell, A; Hijmans, W

    1975-01-01

    Immunoglobulin patterns were investigated in seventy-three volunteers older than 95 years. An idiopathic paraproteinaemia was found in 19% of the cases. A restriction of heterogeneity and an imbalance in the kappa/lambda ratio of the immunoglobulins was seen in a number of other sera. Determinations of immunoglobulin levels in sera of individuals without paraproteinaemia showed an increase in IgA and IgG. The quantitations of the IgG subclasses demonstrated that an increase in the IgG1 and IgG3 subclasses is responsible for the elevated level of the IgG. The variation in the immunoglobulin levels increased significantly with age of IgM and for the three major IgG subclasses. No abnormalities were found in the urine or in the mixed saliva. These results indicate that selective changes in the extent of the antibody-immunoglobulin repertoire characterize the immunoglobulin pattern of ageing man. PMID:1212818

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

    PubMed

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

    2016-05-01

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

  1. Synthesis of immunoglobulins by human endocervix in organ culture.

    PubMed Central

    Cowan, M. E.; Buchan, A.; Skinner, G. R.

    1982-01-01

    The synthesis of immunoglobulins by the uterine cervix was investigated in an endocervical organ-culture system. Using Ouchterlony immunodiffusion gels immunoglobulin G, immunoglobulin A and secretory piece were detected in washings of endocervical explants and in explant incubation medium. Synthesis of immunoglobulin in the organ-culture system was investigated by polyacrylamide-gel electrophoresis of radiolabelled polypeptides; 2 polypeptides co-migrated with the heavy and light chains of a reference polyclonal immunoglobulin G and were confirmed, by use of anti-human globulin and iodinated staphylococcal protein A, to be the heavy and light chains of immunoglobulin G. This experimental system will provide a useful model in future investigations of the efficacy of a local vaccine in human subjects. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:6803822

  2. Synthesis of immunoglobulins by human endocervix in organ culture.

    PubMed

    Cowan, M E; Buchan, A; Skinner, G R

    1982-04-01

    The synthesis of immunoglobulins by the uterine cervix was investigated in an endocervical organ-culture system. Using Ouchterlony immunodiffusion gels immunoglobulin G, immunoglobulin A and secretory piece were detected in washings of endocervical explants and in explant incubation medium. Synthesis of immunoglobulin in the organ-culture system was investigated by polyacrylamide-gel electrophoresis of radiolabelled polypeptides; 2 polypeptides co-migrated with the heavy and light chains of a reference polyclonal immunoglobulin G and were confirmed, by use of anti-human globulin and iodinated staphylococcal protein A, to be the heavy and light chains of immunoglobulin G. This experimental system will provide a useful model in future investigations of the efficacy of a local vaccine in human subjects.

  3. Fibronectin Aggregation and Assembly

    PubMed Central

    Ohashi, Tomoo; Erickson, Harold P.

    2011-01-01

    The mechanism of fibronectin (FN) assembly and the self-association sites are still unclear and contradictory, although the N-terminal 70-kDa region (I1–9) is commonly accepted as one of the assembly sites. We previously found that I1–9 binds to superfibronectin, which is an artificial FN aggregate induced by anastellin. In the present study, we found that I1–9 bound to the aggregate formed by anastellin and a small FN fragment, III1–2. An engineered disulfide bond in III2, which stabilizes folding, inhibited aggregation, but a disulfide bond in III1 did not. A gelatin precipitation assay showed that I1–9 did not interact with anastellin, III1, III2, III1–2, or several III1–2 mutants including III1–2KADA. (In contrast to previous studies, we found that the III1–2KADA mutant was identical in conformation to wild-type III1–2.) Because I1–9 only bound to the aggregate and the unfolding of III2 played a role in aggregation, we generated a III2 domain that was destabilized by deletion of the G strand. This mutant bound I1–9 as shown by the gelatin precipitation assay and fluorescence resonance energy transfer analysis, and it inhibited FN matrix assembly when added to cell culture. Next, we introduced disulfide mutations into full-length FN. Three disulfide locks in III2, III3, and III11 were required to dramatically reduce anastellin-induced aggregation. When we tested the disulfide mutants in cell culture, only the disulfide bond in III2 reduced the FN matrix. These results suggest that the unfolding of III2 is one of the key factors for FN aggregation and assembly. PMID:21949131

  4. [Development and study of properties of immunoglobulins against Lassa fever].

    PubMed

    Krasnianskiĭ, V P; Gradoboev, V N; Borisevich, I V; Potryvaeva, N V; Lebedinskaia, E V; Chernikova, N K; Timan'kova, G D

    1997-01-01

    A horse may serve the producer of immune antiserum to Lassa virus. Specific immunoglobulin with at least 1:512 titer of virus-neutralizing antibodies to Lassa fever was obtained by alcohol sedimentation after Cohn from the blood serum of immunized horses. The preparation does not differ from heterologous commercial immunoglobulins. Preclinical studies of immunoglobulin to Lassa fever demonstrated its safety and a high specific activity. The agent can be injected both alone and in combination with virasole.

  5. A beneficial role for immunoglobulin E in host defense against honeybee venom.

    PubMed

    Marichal, Thomas; Starkl, Philipp; Reber, Laurent L; Kalesnikoff, Janet; Oettgen, Hans C; Tsai, Mindy; Metz, Martin; Galli, Stephen J

    2013-11-14

    Allergies are widely considered to be misdirected type 2 immune responses, in which immunoglobulin E (IgE) antibodies are produced against any of a broad range of seemingly harmless antigens. However, components of insect venoms also can sensitize individuals to develop severe IgE-associated allergic reactions, including fatal anaphylaxis, upon subsequent venom exposure. We found that mice injected with amounts of honeybee venom similar to that which could be delivered in one or two stings developed a specific type 2 immune response that increased their resistance to subsequent challenge with potentially lethal amounts of the venom. Our data indicate that IgE antibodies and the high affinity IgE receptor, FcεRI, were essential for such acquired resistance to honeybee venom. The evidence that IgE-dependent immune responses against venom can enhance survival in mice supports the hypothesis that IgE, which also contributes to allergic disorders, has an important function in protection of the host against noxious substances. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Observing Convective Aggregation

    NASA Astrophysics Data System (ADS)

    Holloway, Christopher E.; Wing, Allison A.; Bony, Sandrine; Muller, Caroline; Masunaga, Hirohiko; L'Ecuyer, Tristan S.; Turner, David D.; Zuidema, Paquita

    2017-06-01

    Convective self-aggregation, the spontaneous organization of initially scattered convection into isolated convective clusters despite spatially homogeneous boundary conditions and forcing, was first recognized and studied in idealized numerical simulations. While there is a rich history of observational work on convective clustering and organization, there have been only a few studies that have analyzed observations to look specifically for processes related to self-aggregation in models. Here we review observational work in both of these categories and motivate the need for more of this work. We acknowledge that self-aggregation may appear to be far-removed from observed convective organization in terms of time scales, initial conditions, initiation processes, and mean state extremes, but we argue that these differences vary greatly across the diverse range of model simulations in the literature and that these comparisons are already offering important insights into real tropical phenomena. Some preliminary new findings are presented, including results showing that a self-aggregation simulation with square geometry has too broad distribution of humidity and is too dry in the driest regions when compared with radiosonde records from Nauru, while an elongated channel simulation has realistic representations of atmospheric humidity and its variability. We discuss recent work increasing our understanding of how organized convection and climate change may interact, and how model discrepancies related to this question are prompting interest in observational comparisons. We also propose possible future directions for observational work related to convective aggregation, including novel satellite approaches and a ground-based observational network.

  7. Observing convective aggregation

    NASA Astrophysics Data System (ADS)

    Holloway, Christopher; Wing, Allison; Bony, Sandrine; Muller, Caroline; Masunaga, Hirohiko; L'Ecuyer, Tristan; Turner, David; Zuidema, Paquita

    2017-04-01

    Convective self-aggregation was first recognized and studied in idealized numerical simulations. While there is a rich history of observational work on convective clustering and organization, there have been only a few studies that have analyzed observations to look specifically for processes related to self-aggregation in models. Here we review observational work in both of these categories and motivate the need for more of this work. We acknowledge that self-aggregation may appear to be far-removed from observed convective organization in terms of time scales, initial conditions, initiation processes, and mean state extremes, but we argue that these differences vary greatly across the diverse range of model simulations in the literature and that these comparisons are already offering important insights into real tropical phenomena. Some preliminary new findings are presented, including results showing that a self-aggregation simulation with square geometry has too broad a distribution of humidity and is too dry in the driest regions when compared with radiosonde records from Nauru, while an elongated channel simulation has realistic representations of atmospheric humidity and its variability. We discuss recent work increasing our understanding of how organized convection and climate change may interact, and how model discrepancies related to this question are prompting interest in observational comparisons. We also propose possible future directions for observational work related to convective aggregation, including novel satellite approaches and a ground-based observational network.

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

    PubMed

    Fleenor, W A; Stott, G H

    1980-06-01

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

  9. Single radial immunodiffusion analysis for quantitation of colostral immunoglobulin concentration.

    PubMed

    Fleenor, W A; Stott, G H

    1981-05-01

    Relative accuracy of the single radial immunodiffusion technique to measure immunoglobulin concentrations of colostral preparations (whey, whole, or fat-free) has been assessed. Fresh colostrum samples were analyzed for major constituents. Gammaglobulin as a standard was compared to total immunoglobulin concentration derived from single radial immunodiffusion analysis of colostral preparations with no differences except between standard and whey. Differences were in part from either enhancement or interference of immunoglobulin diffusion by colostral constituents. Removal of casein and fat during whey preparations caused a concentrating effect upon immunoglobulin constituents resulting in exaggerated precipitin rings. Whey has produced unreliable results: therefore, whole colostrum is recommended for single radial immunodiffusion analysis.

  10. Secondary hypogammaglobulinemia in Waldmann's disease treated with subcutaneous immunoglobulins.

    PubMed

    Patuzzo, G; Tinazzi, E; Micheletti, M; Puccetti, A; Lunardi, C

    2016-03-01

    Primary intestinal lymphangiectasia (PIL) is rare disorder characterized by congenital malformation or obstruction of intestinal lymphatic drainage; it is responsible for protein losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL management. The administration of intravenous immunoglobulins does not always lead to satisfactory plasma levels and therefore the replacement therapy with immunoglobulins is controversial. We describe here the case of a patient with PIL and severe hypogammaglobulinemia treated with immunoglobulins. The striking aspect of this case is the clinical and serological benefit obtained with the subcutaneous compared to the intravenous immunoglobulins administration.

  11. Reactions of immunoglobulin G-binding ligands with platelets and platelet-associated immunoglobulin G.

    PubMed Central

    Rosse, W F; Devine, D V; Ware, R

    1984-01-01

    Immunoglobulin G (IgG) bound to platelets is usually detected by one of two general methods: binding of labeled anti-IgG or consumption of anti-IgG. The latter method gives, in general, values 5-10-fold greater than the former under the same conditions. To investigate these discrepancies, we have compared the detection of platelet-bound IgG by a labeled anti-IgG binding assay and by a quantitative antiglobulin consumption test using the same antibodies. The interaction of 125I-labeled monoclonal anti-IgG or polyclonal anti-IgG with washed and IgG-coated platelets was studied. The binding of these ligands to washed normal platelets was largely (50-80%) nonspecific; the binding was not saturable and was only partially inhibitable by excess unlabeled anti-IgG. The binding of anti-IgG to platelets coated with anti-PIA1, a platelet-specific IgG antibody, appeared to be saturable and inhibitable; the dissociation constant (KD) of this IgG-anti-IgG reaction was 4.9 X 10(-9) for monoclonal and 1.4 X 10(-7) for polyclonal anti-IgG. The ratio of sites present on the membrane (determined by 131I-labeled anti-PIA1) to the number of binding sites for anti-IgG determined by Scatchard analysis was 0.53 for monoclonal anti-IgG and 1.3 for polyclonal anti-IgG. The binding of monoclonal anti-IgG to platelet-bound immune complexes or IgG aggregates appeared to be complex. 131I-Labeled IgG was affixed to platelets and was detected by three tests: direct binding of radiolabeled monoclonal anti-IgG and quantitative antiglobulin consumption (QAC) tests, which were quantitated either by measuring directly the amount of radiolabeled anti-IgG consumed from fluid phase (direct QAC), or indirectly by reference to a calibration curve relating the consumption of anti-IgG by known amounts of fluid-phase, non-immune IgG (indirect QAC). The amount of platelet-bound IgG detected by the direct binding of 125I-labeled monoclonal anti-IgG and by the direct QAC approximated that known to be bound to

  12. Collaborative study to establish human immunoglobulin BRP batch 3 and human immunoglobulin (molecular size) BRP batch 1.

    PubMed

    Sandberg, E; Daas, A; Behr-Gross, M-E

    2006-11-01

    A study was carried out by the European Directorate for the Quality of Medicines (EDQM) as part of the joint Biological Standardisation Programme of the Council of Europe and the European Commission with the aim to establish replacement batches of the European Pharmacopoeia (Ph. Eur.) human immunoglobulin Biological Reference Preparation (BRP) batch 2. Twenty-eight laboratories participated in this study. The suitability of the candidate reference preparations to serve as working references in the tests for distribution of the molecular size, anticomplementary activity and Fc function, in accordance with the specifications of the Ph. Eur. monographs Human normal immunoglobulin for intravenous administration (0918), Human normal immunoglobulin (0338) and Anti-T lymphocyte immunoglobulin for human use, animal (1928) was demonstrated. The candidates were therefore established as human immunoglobulin BRP batch 3 and Human immunoglobulin (molecular size) BRP batch 1. The prescribed use of the latter BRP is limited to the test for distribution of molecular size.

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

    NASA Technical Reports Server (NTRS)

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

    2002-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2002-01-01

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

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

    PubMed

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

    2016-01-01

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

  16. [Secretory immunoglobulin A in amniotic fluid].

    PubMed

    Briese, V; Straube, W; Brock, J; Lorenz, U

    1983-01-01

    Secretory immunoglobulin A (S-IgA) was estimated in amniotic fluid samples by means of the single radial immunodiffusion according to Mancini. A monospecific antiserum against human secretory component was used. 163 amniotic fluid samples from normal pregnancies and risk pregnancies respectively were investigated. Within the 3rd trimenon the S-IgA content in amniotic fluid increased significantly. With respect to literature and examinations performed previously a connection between S-IgA content in amniotic fluid and fetal lung maturity seems to be possible.

  17. Secondary erythromelalgia successfully treated with intravenous immunoglobulin.

    PubMed

    Moody, Shadé; Pacheco, Susan; Butler, Ian J; Koenig, Mary Kay

    2012-07-01

    Erythromelalgia is a rare condition characterized by episodic painful erythema and warmth often affecting, but not limited to, the distal extremities. This condition is notoriously difficult to treat. We report a young female patient with seronegative polyarthritis who presented with a 6-year history of recurrent bouts of painful erythema and swelling often triggered by minor trauma. An extensive evaluation was unremarkable. Several medical therapies provided limited and inconsistent relief of her symptoms over many years. Treatment with intravenous immunoglobulin significantly decreased the frequency and severity of her symptoms.

  18. New Regulatory Roles of Galectin-3 in High-Affinity IgE Receptor Signaling.

    PubMed

    Bambouskova, Monika; Polakovicova, Iva; Halova, Ivana; Goel, Gautam; Draberova, Lubica; Bugajev, Viktor; Doan, Aivi; Utekal, Pavol; Gardet, Agnes; Xavier, Ramnik J; Draber, Petr

    2016-05-01

    Aggregation of the high-affinity receptor for IgE (FcεRI) in mast cells initiates activation events that lead to degranulation and release of inflammatory mediators. To better understand the signaling pathways and genes involved in mast cell activation, we developed a high-throughput mast cell degranulation assay suitable for RNA interference experiments using lentivirus-based short hairpin RNA (shRNA) delivery. We tested 432 shRNAs specific for 144 selected genes for effects on FcεRI-mediated mast cell degranulation and identified 15 potential regulators. In further studies, we focused on galectin-3 (Gal3), identified in this study as a negative regulator of mast cell degranulation. FcεRI-activated cells with Gal3 knockdown exhibited upregulated tyrosine phosphorylation of spleen tyrosine kinase and several other signal transduction molecules and enhanced calcium response. We show that Gal3 promotes internalization of IgE-FcεRI complexes; this may be related to our finding that Gal3 is a positive regulator of FcεRI ubiquitination. Furthermore, we found that Gal3 facilitates mast cell adhesion and motility on fibronectin but negatively regulates antigen-induced chemotaxis. The combined data indicate that Gal3 is involved in both positive and negative regulation of FcεRI-mediated signaling events in mast cells.

  19. New Regulatory Roles of Galectin-3 in High-Affinity IgE Receptor Signaling

    PubMed Central

    Bambouskova, Monika; Polakovicova, Iva; Halova, Ivana; Goel, Gautam; Draberova, Lubica; Bugajev, Viktor; Doan, Aivi; Utekal, Pavol; Gardet, Agnes; Xavier, Ramnik J.

    2016-01-01

    Aggregation of the high-affinity receptor for IgE (FcεRI) in mast cells initiates activation events that lead to degranulation and release of inflammatory mediators. To better understand the signaling pathways and genes involved in mast cell activation, we developed a high-throughput mast cell degranulation assay suitable for RNA interference experiments using lentivirus-based short hairpin RNA (shRNA) delivery. We tested 432 shRNAs specific for 144 selected genes for effects on FcεRI-mediated mast cell degranulation and identified 15 potential regulators. In further studies, we focused on galectin-3 (Gal3), identified in this study as a negative regulator of mast cell degranulation. FcεRI-activated cells with Gal3 knockdown exhibited upregulated tyrosine phosphorylation of spleen tyrosine kinase and several other signal transduction molecules and enhanced calcium response. We show that Gal3 promotes internalization of IgE-FcεRI complexes; this may be related to our finding that Gal3 is a positive regulator of FcεRI ubiquitination. Furthermore, we found that Gal3 facilitates mast cell adhesion and motility on fibronectin but negatively regulates antigen-induced chemotaxis. The combined data indicate that Gal3 is involved in both positive and negative regulation of FcεRI-mediated signaling events in mast cells. PMID:26929198

  20. Morphine modulates mesangial immunoglobulin G uptake in rats with antithymocyte serum-induced mesangial cell injury.

    PubMed

    Singhal, P C; Pan, C Q; Sagar, S; Valderrama, E; Stahl, R A

    1996-01-01

    The glomerular mesangium is an important site of activity in patients with heroin addiction. We studied the effect of morphine, a metabolite of heroin, on the mesangial immunoglobulin G aggregate uptake in a model of specific mesangial cell injury. Isolated specific mesangial cell injury was developed in Lewis rats by injecting intravenously antithymocyte serum (ATS). Forty-eight hours later, radioiodinated, heat aggregated immunoglobulin G (AHIgG125I) was administered (20 mg/100 g i.v.) by tail vein. At 4 and 24 h, kidneys, liver, and spleen were removed, glomeruli isolated, and the radioactivity measured. Blood levels of AHIgG125I were measured at 0, 4 and 24 h. For ultrastructural studies, IgG-coated gold particles were injected, and the mesangial circulation was studied. At 4 h, ATS-treated rats showed a lower (p < 0.02) accumulation of AHIgG125I in the mesangium when compared with control rats (controls 511,012 +/- 10,807 vs. ATS 464,614 +/- 7,944 cpm/g glomerular protein). ATS plus morphine treated rats showed a higher (p < 0.01) accumulation of of AHIgG125I when compared with rats treated with AS alone. Even at 24, h morphine-treated ATS rats showed a higher accumulation of AHIgG125I when compared with those treated with ATS alone. Ultrastructural studies showed aggregation of IgG-coated gold particles in the mesangial cell endolysosomes of control rats. Our results suggest that macromolecules may dwell longer in the mesangium of rats with intact mesangial cells. This increase in transit time may be related to the uptake of these macromolecules by mesangial cells. Morphine seems to enhance the accumulation of macromolecules in the mesangium, independent of its action on mesangial cells.

  1. Optimization by factorial analysis of caprylic acid precipitation of non-immunoglobulins from hyperimmune equine plasma for antivenom preparation.

    PubMed

    Nudel, B C; Perdoménico, C; Iácono, R; Cascone, O

    2012-01-01

    Optimization of caprylic acid precipitation of equine plasma non-immunoglobulin proteins for antivenom preparation was achieved by regression analysis of the responses of three highly significant factors assayed by factorial design. The factors studied were caprylic acid concentration, plasma pH and temperature, and their response was assessed in terms of filtration speed, residual albumin, total protein content and turbidity. The results evidenced that the three variables are involved in the precipitation process. Moreover, the factors displayed significant interactions, indicating that their levels distinctly affect the optimization procedure. The best combination was 3% caprylic acid, 37 °C and plasma pH 4.9; under these conditions, all immunoglobulins and only 0.1% albumin remained in the supernatant, in a very fast and simple procedure. After formulation, the antivenom obtained by this procedure presented full lethality neutralizing activity and absence of protein aggregates. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Technology meets aggregate

    SciTech Connect

    Wilson, C.; Swan, C.

    2007-07-01

    New technology carried out at Tufts University and the University of Massachusetts on synthetic lightweight aggregate has created material from various qualities of fly ash from coal-fired power plants for use in different engineered applications. In pilot scale manufacturing tests an 'SLA' containing 80% fly ash and 20% mixed plastic waste from packaging was produced by 'dry blending' mixed plastic with high carbon fly ash. A trial run was completed to produce concrete masonry unit (CMU) blocks at a full-scale facility. It has been shown that SLA can be used as a partial substitution of a traditional stone aggregate in hot asphalt mix. 1 fig., 2 photos.

  3. 21 CFR 866.5530 - Immunoglobulin G (Fc fragment specific) immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... immunoglobulin G (resulting from breakdown of immunoglobulin G antibodies) in urine, serum, and other body fluids. Measurement of immunoglobulin G Fc fragments aids in the diagnosis of plasma cell antibody-forming...

  4. [Glomerulopathies with organized monoclonal immunoglobulin deposits].

    PubMed

    Touchard, Guy; Bridoux, Frank; Goujon, Jean-Michel

    2016-02-01

    The spectrum of glomerular disorders with organized immunoglobulin (Ig) deposits is heterogeneous. It encompasses 2 mains categories: glomerulopathies with fibrillary deposits are mostly represented by immunoglobulinic amyloidosis (most commonly AL amyloidosis, characterized by monoclonal light chain deposits often of the lambda isotype), and pseudo-amyloid fibrillary glomerulonephritis in which deposits predominantly contain polyclonal IgG4. Glomerulopathies with microtubular deposits include cryoglobulinemic glomerulonephritis (type I and type II, with or without detectable serum cryoglobulin) and glomerulonephritis with organized microtubular monoclonal Ig deposits (GOMMID) also referred to as immunotactoid glomerulopathy. Pathological diagnosis requires meticulous studies by light microscopy (with systematic Congo red staining), immunofluorescence with specific conjugates, and electron microscopy. Ultrastructural studies are required to differentiate amyloid fibrils (8 to 10 nm in external diameter), pseudo-amyloid fibrils (15-20 nm) and microtubules (10 to 50 nm in external diameter, with a central hollow core). Glomerular deposits in type I cryoglobulinemic glomerulonephritis are arranged into parallel straight microtubules similar to those observed in GOMMID, but with different topography that allows distinction between the two entities. Glomerular substructures composed of circulating Igs should be distinguished from collagen fibrils that are commonly observed in glomerular disorders with or without deposition of monoclonal or polyclonal Igs. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  5. The Immunoglobulins of Cold-Blooded Vertebrates

    PubMed Central

    Pettinello, Rita; Dooley, Helen

    2014-01-01

    Although lymphocyte-like cells secreting somatically-recombining receptors have been identified in the jawless fishes (hagfish and lamprey), the cartilaginous fishes (sharks, skates, rays and chimaera) are the most phylogenetically distant group relative to mammals in which bona fide immunoglobulins (Igs) have been found. Studies of the antibodies and humoral immune responses of cartilaginous fishes and other cold-blooded vertebrates (bony fishes, amphibians and reptiles) are not only revealing information about the emergence and roles of the different Ig heavy and light chain isotypes, but also the evolution of specialised adaptive features such as isotype switching, somatic hypermutation and affinity maturation. It is becoming increasingly apparent that while the adaptive immune response in these vertebrate lineages arose a long time ago, it is most definitely not primitive and has evolved to become complex and sophisticated. This review will summarise what is currently known about the immunoglobulins of cold-blooded vertebrates and highlight the differences, and commonalities, between these and more “conventional” mammalian species. PMID:25427250

  6. Autoantibodies and immunoglobulins among atomic bomb survivors

    SciTech Connect

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

    1994-01-01

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

  7. Cloned transchromosomic calves producing human immunoglobulin.

    PubMed

    Kuroiwa, Yoshimi; Kasinathan, Poothappillai; Choi, Yoon J; Naeem, Rizwan; Tomizuka, Kazuma; Sullivan, Eddie J; Knott, Jason G; Duteau, Anae; Goldsby, Richard A; Osborne, Barbara A; Ishida, Isao; Robl, James M

    2002-09-01

    Human polyclonal antibodies (hPABs) are useful therapeutics, but because they are available only from human donors, their supply and application is limited. To address this need, we prepared a human artificial chromosome (HAC) vector containing the entire unrearranged sequences of the human immunoglobulin (hIg) heavy-chain (H) and lambda (lambda) light-chain loci. The HAC vector was introduced into bovine primary fetal fibroblasts using a microcell-mediated chromosome transfer (MMCT) approach. Primary selection was carried out, and the cells were used to produce cloned bovine fetuses. Secondary selection was done on the regenerated fetal cell lines, which were then used to produce four healthy transchromosomic (Tc) calves. The HAC was retained at a high rate (78-100% of cells) in calves and the hIg loci underwent rearrangement and expressed diversified transcripts. Human immunoglobulin proteins were detected in the blood of newborn calves. The production of Tc calves is an important step in the development of a system for producing therapeutic hPABs.

  8. Passive transfer of colostral immunoglobulins in calves.

    PubMed

    Weaver, D M; Tyler, J W; VanMetre, D C; Hostetler, D E; Barrington, G M

    2000-01-01

    Passive transfer of colostral immunoglobulins has long been accepted as imperative to optimal calf health. Many factors, including timing of colostrum ingestion, the method and volume of colostrum administration, the immunoglobulin concentration of the colostrum ingested, and the age of the dam have been implicated in affecting the optimization of absorption. The practice of colostrum pooling, the breed and presence of the dam, and the presence of respiratory acidosis in the calf also may affect passive transfer. Various tests have been reported to accurately measure passive transfer status in neonatal calves. The radial immunodiffusion and the enzyme-linked immunosorbent assay (ELISA) are the only tests that directly measure serum IgG concentration. All other available tests including serum total solids by refractometry, sodium sulfite turbidity test, zinc sulfate turbidity test, serum gamma-glutamyl transferase activity, and whole blood glutaraldehyde gelation estimate serum IgG concentration based on concentration of total globulins or other proteins whose passive transfer is statistically associated with that of IgG. This paper presents a comprehensive review of the literature of passive transfer in calves including factors that affect passive transfer status, testing modalities, effects of failure of passive transfer on baseline mortality, consequences of failure of passive transfer, and some treatment options. Many previously accepted truisms regarding passive transfer in calves should be rejected based on the results of recent research.

  9. The immunoglobulins of cold-blooded vertebrates.

    PubMed

    Pettinello, Rita; Dooley, Helen

    2014-11-24

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

  10. Intravenous immunoglobulin therapy and systemic lupus erythematosus.

    PubMed

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

    2005-12-01

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

  11. Prostaglandin E receptor subtype 4 regulates lipid droplet size and mitochondrial activity in murine subcutaneous white adipose tissue.

    PubMed

    Ying, Fan; Cai, Yin; Cai, Yu; Wang, Yu; Tang, Eva Hoi Ching

    2017-09-01

    The purpose of this study was to investigate whether genetic ablation of prostaglandin E receptor subtype 4 (EP4) affects white adipose tissue (WAT) remodeling mediated by β3-adrenergic stimulation. The selective β3-adrenergic agonist, CL316243 (1 mg/kg/d, i.p.) caused a greater increase in metabolic rate in EP4-knockout mice. CL316243 fragmented the unilocular lipid droplet into multilocular lipid vacuoles and increased mitochondrial biogenesis and its activity. These changes were amplified in mice with EP4 deficiency and were selectively seen in subcutaneous WAT. The expression of fat-specific protein (FSP)-27, a protein that promotes fusion of triglycerides and formation of unilocular lipid droplets were diminished, whereas the expression of phosphorylated AMPK, the upstream regulator of FSP27, was enhanced in EP4-deficient mice. The present study showed that EP4 acts as a negative regulator of WAT remodeling, it tightly coordinates rates of triglyceride storage in lipid droplets and mitochondrial respiratory function in subcutaneous white adipocytes through the phosphorylated AMPK-FSP27 signaling axis. Thus, deletion of EP4 increases mitochondrial biogenesis and oxidative capacity in WAT, and fat mass loss ensues in mice.-Ying, F., Cai, Y., Cai, Y., Wang, Y., Tang, E. H. C. Prostaglandin E receptor subtype 4 regulates lipid droplet size and mitochondrial activity in murine subcutaneous white adipose tissue. © FASEB.

  12. Responsivity to PGE2 labor induction involves concomitant differential prostaglandin E receptor gene expression in cervix and myometrium.

    PubMed

    Konopka, C K; Glanzner, W G; Rigo, M L; Rovani, M T; Comim, F V; Gonçalves, P B D; Morais, E N; Antoniazzi, A Q; Mello, C F; Cruz, I B M

    2015-09-10

    Prostaglandin E2 (dinoprostone) is largely used for labor induction. However, one-third of patients do not respond to treatment. One cause of this poor response may be associated with changes in regulation of prostaglandin E receptors (EP1-4). In this study, we investigated EP mRNA expression in the uterine cervix and lower uterine segment myometrium for term births. Biopsies were obtained from women with successful (responders) and failed (non-responders) dinoprostone labor induction, while women that underwent spontaneous labor were included as controls. EP1 mRNA was upregulated in the cervical tissue of women who did not respond to dinoprostone induction. In addition, in the myometrium, significantly higher levels of EP3 mRNA were observed in women treated with dinoprostone, independent of their responsiveness. Dinoprostone-responders presented 3.6-fold higher levels of EP3 mRNA expression than the spontaneous labor group. Significantly higher levels of EP3 mRNA in the myometrium of the dinoprostone-treated group indicated that dinoprostone may regulate the EP3 gene on the transcriptional level. These results highlight the relationship between EP gene expression and delivery and indicate that understanding the regulation of prostaglandin E receptors may lead to improved labor induction.

  13. The role of Ly49E receptor expression on murine intraepithelial lymphocytes in intestinal cancer development and progression.

    PubMed

    Van Acker, Aline; Louagie, Els; Filtjens, Jessica; Taveirne, Sylvie; Van Ammel, Els; Kerre, Tessa; Elewaut, Dirk; Taghon, Tom; Vandekerckhove, Bart; Plum, Jean; Leclercq, Georges

    2016-11-01

    Ly49E is a member of the Ly49 family of NK receptors and is distinct from other members of this family on the basis of its structural properties, expression pattern and ligand recognition. Importantly, Ly49E receptor expression is high on small intestinal and colonic intraepithelial lymphocytes (IELs). Intestinal IELs are regulators of the mucosal immune system and contribute to front-line defense at the mucosal barrier, including anti-tumor immune response. Whereas most Ly49 receptors have MHC class-I ligands, we showed that Ly49E is instead triggered by urokinase plasminogen activator (uPA). uPA has been extensively implicated in tumor development, where increased uPA expression correlates with poor prognosis. As such, we investigated the role of Ly49E receptor expression on intestinal IELs in the anti-tumor immune response. For this purpose, we compared Ly49E wild-type mice to Ly49E knockout mice in two established tumor models: Apc(Min/+)-mediated and azoxymethane-induced intestinal cancer. Our results indicate that Ly49E expression on IELs does not influence the development or progression of intestinal cancer.

  14. Aggregates, broccoli and cauliflower

    NASA Astrophysics Data System (ADS)

    Grey, Francois; Kjems, Jørgen K.

    1989-09-01

    Naturally grown structures with fractal characters like broccoli and cauliflower are discussed and compared with DLA-type aggregates. It is suggested that the branching density can be used to characterize the growth process and an experimental method to determine this parameter is proposed.

  15. OCULAR MANIFESTATIONS OF MONOCLONAL IMMUNOGLOBULIN LIGHT CHAIN DEPOSITION DISEASE.

    PubMed

    Dhrami-Gavazi, Elona; Freund, K Bailey; Lee, Winston; Cohen, Ben Z; Seshan, Surya V; Yannuzzi, Lawrence A

    2017-01-01

    To demonstrate unusual retinal findings in a patient with progressive renal failure due to idiopathic monoclonal immunoglobulin light chain deposition disease, using multimodal imaging. Observational case report of a 43-year-old white man with renal failure due to light chain deposition disease. His course over 6 years was documented with multimodal imaging including fundus photography, fundus autofluorescence, fluorescein angiography, and spectral domain optical coherence tomography. Additional evaluations included ocular ultrasound, electroretinography, positron emission tomography, serum protein electrophoreses, skeletal surveys to detect osteolytic lesions, and renal, liver, and rectal biopsies in search of amyloid. The patient's ocular course mirrored the severity of his renal dysfunction for which he required a renal transplant. Changes observed in the native kidney recurred in the transplant 2 years later, as evidenced by immunohistochemistry, revealing thick linear deposits of kappa chains, with no complement, overlying the glomerular basement membrane. The systemic workup was negative for amyloid but showed an overwhelming ratio of kappa to lambda light chains on serum protein electrophoreses and no clinical signs of plasma cell dyscrasias, all consistent with idiopathic light chain deposition disease. The patient presented with a generalized, bilateral "leopard-spot" fundus appearance on fundus autofluorescence, striking globular subretinal deposits on spectral domain optical coherence tomography, and subfoveal subretinal fluid without retinal pigment epithelium detachment or choroidal effusions. The subfoveal fluid did not respond to intravitreal injections of antiangiogenic agents or steroids but resolved after renal transplantation. A temporary posttransplant visual improvement was associated with lessening of the subretinal drusenoid deposits demonstrated by multimodal imaging. The terminal vision deterioration was associated with amorphous

  16. The importance of sequence diversity in the aggregation and evolution of proteins.

    PubMed

    Wright, Caroline F; Teichmann, Sarah A; Clarke, Jane; Dobson, Christopher M

    2005-12-08

    Incorrect folding of proteins, leading to aggregation and amyloid formation, is associated with a group of highly debilitating medical conditions including Alzheimer's disease and late-onset diabetes. The issue of how unwanted protein association is normally avoided in a living system is particularly significant in the context of the evolution of multidomain proteins, which account for over 70% of all eukaryotic proteins, where the effective local protein concentration in the vicinity of each domain is very high. Here we describe the aggregation kinetics of multidomain protein constructs of immunoglobulin domains and the ability of different homologous domains to aggregate together. We show that aggregation of these proteins is a specific process and that the efficiency of coaggregation between different domains decreases markedly with decreasing sequence identity. Thus, whereas immunoglobulin domains with more than about 70% identity are highly prone to coaggregation, those with less than 30-40% sequence identity do not detectably interact. A bioinformatics analysis of consecutive homologous domains in large multidomain proteins shows that such domains almost exclusively have sequence identities of less than 40%, in other words below the level at which coaggregation is likely to be efficient. We propose that such low sequence identities could have a crucial and general role in safeguarding proteins against misfolding and aggregation.

  17. Osmotic nephrosis due to high-dose immunoglobulin therapy containing sucrose (but not with glycine) in a patient with immunoglobulin A nephritis.

    PubMed

    Hansen-Schmidt, S; Silomon, J; Keller, F

    1996-09-01

    Acute renal failure has been described as a complication of immunoglobulin therapy. It is not clear whether the immunoglobulin per se or the sucrose that is used as a stabilizer is the cause. We describe a patient with immunoglobulin A nephropathy who was treated with sucrose-containing immunoglobulin. He developed acute renal failure with osmotic nephrosis found on kidney biopsy. When using a glycine-containing immunoglobulin no acute renal impairment was observed in this patient.

  18. Impact of vegetarian diet on serum immunoglobulin levels in children.

    PubMed

    Gorczyca, Daiva; Prescha, Anna; Szeremeta, Karolina

    2013-03-01

    Nutrition plays an important role in immune response. We evaluated the effect of nutrient intake on serum immunoglobulin levels in vegetarian and omnivore children. Serum immunoglobulin levels and iron status were estimated in 22 vegetarian and 18 omnivore children. Seven-day food records were used to assess the diet. There were no significant differences in serum IgA, IgM, and IgG levels between groups of children. Serum immunoglobulin levels were lower in vegetarian children with iron deficiency in comparison with those without iron deficiency. In the vegetarians, IgG level correlated positively with energy, zinc, copper, and vitamin B(6) intake. In the omnivores, these correlations were stronger with IgM level. Despite negligible differences in serum immunoglobulin levels between vegetarian and omnivore children, the impact of several nutrient intakes on IgM and IgG levels differed between groups. Low iron status in vegetarian children can lead to decreased immunoglobulin levels.

  19. Genomic structure and expression of immunoglobulins in Squamata.

    PubMed

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

    2016-04-01

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

  20. Specific absorption of human serum albumin, immunoglobulin A, and immunoglobulin G with selected strains of group A and G streptococci.

    PubMed Central

    Kronvall, G; Simmons, A; Myhre, E B; Jonsson, S

    1979-01-01

    Five gram-positive bacterial strains were selected for absorption studies of human serum samples. Strain AR1 (group A, M-type 1) and G148 (group G), with strong immunoglobulin G (IgG) binding capacities, and strain AW43 (group A, M-type 60), binding both IgA1 and IgA2, were compared with Staphylococcus aureus Cowan I and with Staphylococcus epidermidis L603. Both AR1 and G148 were capable of completely absorbing out serum IgG. In contrast, S. aureus Cowan I left a fraction unabsorbed, as expected from its known lack of IgG3 binding. Strain AW43 absorbed out all serum IgA, using a 10-microliter bacterial pellet for 20 microliter of serum. Serum IgM levels were slightly reduced by S. aureus Cowan I absorption. On the basis of the experiments, a bacterial mixture was designed consisting of S. aureus Cowan I and group A streptococcus strains AR1 and AW43, with absorption characteristics suitable for use in discriminating between early IgM and late IgG and IgA immune responses in routine serological work. A new type of bacteria-mammalian protein binding was discovered. Human serum albumin was completely absorbed out by strain G148 and to a lesser extent by strain AR1 and AW43. S. aureus Cowan I and S. epidermidis were negative. The binding capacity of G148 for albumin equalled that of Cowan I for IgG. The binding pattern of albumin to the strains was different from those of IgG, IgA, IgM, fibrinogen, haptoglobin, or aggregated beta 2-microglobulin and therefore seems to represent another type of bacterial-mammalian interaction with a specific albumin receptor on the surface of streptococci. Images PMID:383609

  1. Isolation of the serotoninergic 5-HT4(e) receptor from human heart and comparative analysis of its pharmacological profile in C6-glial and CHO cell lines

    PubMed Central

    Mialet, Jeanne; Berque-Bestel, Isabelle; Eftekhari, Pierre; Gastineau, Monique; Giner, Mireille; Dahmoune, Yamina; Donzeau-Gouge, Patrick; Hoebeke, Johan; Langlois, Michel; Sicsic, Sames; Fischmeister, Rodolphe; Lezoualc'h, Frank

    2000-01-01

    RT–PCR technique was used to clone the human 5-HT4(e) receptor (h5-HT4(e)) from heart atrium. We showed that this h5-HT4(e) receptor splice variant is restricted to brain and heart atrium. Recombinant h5-HT4(e) receptor was stably expressed in CHO and C6-glial cell lines at 347 and 88 fmol mg−1 protein, respectively. Expression of h5-HT4(e) receptors at the cell membrane was confirmed by immunoblotting. The receptor binding profile, determined by competition with [3H]-GR113808 of a number of 5-HT4 ligands, was consistent with that previously reported for other 5-HT4 receptor isoforms. Surprisingly, we found that the rank order of potencies (EC50) of 5-HT4 agonists obtained from adenylyl cyclase functional assays was inversely correlated to their rank order of affinities (Ki) obtained from binding assays. Furthermore, EC50 values for 5-HT, renzapride and cisapride were 2 fold lower in C6-glial cells than in CHO cells. ML10302 and renzapride behaved like partial agonists on the h5-HT4(e) receptor. These results are in agreement with the reported low efficacy of the these two compounds on L-type Ca2+ currents and myocyte contractility in human atrium. A constitutive activity of the h5-HT4(e) receptor was observed in CHO cells in the absence of any 5-HT4 ligand and two 5-HT4 antagonists, GR113808 and ML10375, behaved as inverse agonists. These data show that the h5-HT4(e) receptor has a pharmacological profile which is close to the native h5-HT4 receptor in human atrium with a functional potency which is dependent on the cellular context in which the receptor is expressed. PMID:10683202

  2. Determination of soluble immunoglobulin G in bovine colostrum products by Protein G affinity chromatography-turbidity correction and method validation.

    PubMed

    Holland, Patrick T; Cargill, Anne; Selwood, Andrew I; Arnold, Kate; Krammer, Jacqueline L; Pearce, Kevin N

    2011-05-25

    Immunoglobulin-containing food products and nutraceuticals such as bovine colostrum are of interest to consumers as they may provide health benefits. Commercial scale colostrum products are valued for their immunoglobulin G (IgG) content and therefore require accurate analysis. One of the most commonly used methods for determining total soluble IgG in colostrum products is based on affinity chromatography using a Protein G column and UV detection. This paper documents improvements to the accuracy of the Protein G analysis of IgG in colostrum products, especially those containing aggregated forms of IgG. Capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) analysis confirmed that aggregated IgG measured by Protein G does not contain significant amounts of casein or other milk proteins. Size exclusion chromatography identified the content of soluble IgG as mainly monomeric IgG and aggregated material MW > 450 kDa with small amounts of dimer and trimer. The turbidity of the eluting IgG, mainly associated with aggregated IgG, had a significant effect on the quantitative results. Practical techniques were developed to correct affinity LC data for turbidity on an accurate, consistent, and efficient basis. The method was validated in two laboratories using a variety of colostrum powders. Precision for IgG was 2-3% (RSD(r)) and 3-12% (RSD(R)). Recovery was 100.2 ± 2.4% (mean ± RSD, n = 10). Greater amounts of aggregated IgG were solubilized by a higher solution:sample ratio and extended times of mixing or sonication, especially for freeze-dried material. It is concluded that the method without acid precipitation and with turbidity correction provides accurate, precise, and robust data for total soluble IgG and is suitable for product specification and quality control of colostrum products.

  3. The antigen-binding fragment of human gamma immunoglobulin prevents amyloid β-peptide folding into β-sheet to form oligomers

    PubMed Central

    Valls-Comamala, Victòria; Guivernau, Biuse; Bonet, Jaume; Puig, Marta; Perálvarez-Marín, Alex; Palomer, Ernest; Fernàndez-Busquets, Xavier; Altafaj, Xavier; Tajes, Marta; Puig-Pijoan, Albert; Vicente, Rubén; Oliva, Baldomero; Muñoz, Francisco J.

    2017-01-01

    The amyloid beta-peptide (Aβ) plays a leading role in Alzheimer's disease (AD) physiopathology. Even though monomeric forms of Aβ are harmless to cells, Aβ can aggregate into β-sheet oligomers and fibrils, which are both neurotoxic. Therefore, one of the main therapeutic approaches to cure or delay AD onset and progression is targeting Aβ aggregation. In the present study, we show that a pool of human gamma immunoglobulins (IgG) protected cortical neurons from the challenge with Aβ oligomers, as assayed by MTT reduction, caspase-3 activation and cytoskeleton integrity. In addition, we report the inhibitory effect of IgG on Aβ aggregation, as shown by Thioflavin T assay, size exclusion chromatography and atomic force microscopy. Similar results were obtained with Palivizumab, a human anti-sincitial virus antibody. In order to dissect the important domains, we cleaved the pool of human IgG with papain to obtain Fab and Fc fragments. Using these cleaved fragments, we functionally identified Fab as the immunoglobulin fragment inhibiting Aβ aggregation, a result that was further confirmed by an in silico structural model. Interestingly, bioinformatic tools show a highly conserved structure able to bind amyloid in the Fab region. Overall, our data strongly support the inhibitory effect of human IgG on Aβ aggregation and its neuroprotective role. PMID:28467807

  4. Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy.

    PubMed

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

    2009-01-21

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) causes progressive or relapsing weakness and numbness of the limbs, developing over at least two months. Uncontrolled studies suggest that intravenous immunoglobulin (IVIg) helps. To review systematically the evidence from randomised controlled trials concerning the efficacy and safety of IVIg in CIDP. We searched the Cochrane Neuromuscular Trials Register, MEDLINE, EMBASE and ISI from January 1985 to May 2008. Randomised controlled studies testing any dose of IVIg versus placebo, plasma exchange or corticosteroids in definite or probable CIDP. Two authors reviewed literature searches to identify potentially relevant trials, scored their quality and extracted data independently. We contacted authors for additional information. Seven randomised controlled trials were considered eligible including 287 participants. These trials were homogeneous and overall quality was high. Five studies on 235 participants compared IVIg against placebo. One trial with 20 participants compared IVIg with plasma exchange and one trial compared IVIg with prednisolone in 32 participants. A significantly higher proportion of participants improved in disability within one month after IVIg treatment as compared with placebo (relative risk 2.40, 95% confidence interval 1.72 to 3.36). Whether all these improvements are equally clinically relevant cannot be deduced from this analysis because each trial used different disability scales and definitions of significant improvement. In three trials including 84 participants the disability could be transformed to the modified Rankin score, on which significantly more patients improved one point after IVIg treatment compared to placebo (relative risk 2.40, 95% confidence interval 0.98 to 5.83). Only one study included in this review had a long-term follow-up. The results of this study suggest that intravenous immunoglobulin improves disability more than placebo over 24 and 48 weeks. The

  5. Circulating and tissue-bound immune complexes in allergic vasculitis: relationship between immunoglobulin class and clinical features.

    PubMed Central

    Kauffmann, R H; Herrmann, W A; Meijer, C J; Daha, M R; Vanes, L A

    1980-01-01

    Sixty-two patients with allergic vasculitis and histological evidence of leukocytoclastic vasculitis were examined to determine whether clinical features, such as course and degree of systemic involvement, could be related to the class of the immunoglobulins in immune complexes (IC) in both the circulation and the vessel wall. Circulating IC were detected with the 125I-C1q-binding assay (C1q-BA), an anti-IgA inhibition binding assay (a-IgA-Inh BA) and the conglutinin-binding assay (Con-BA). Stabilized heat-aggregated IgG, IgA and IgM were used to determine the immunoglobulin class specificity of these assays. With the C1q-BA only aggregated IgG were detected, with the a-IgA-Inh Ba only aggregates containing IgA. With the Con-BA IgG, IgA or IgM in reactive aggregates were identified with class-specific antibodies. For patients with acute cutaneous vasculitis all assays were negative. The a-IgA-Inh BA was frequently positive in sera of patients with chronic cutaneous and acute systemic vasculitis; in the latter group conglutinin-binding IC of the IgG, IgA and IgM class were also detected. Levels in the C1q-BA were high for patients with chronic systemic vasculitis. Comparison of the results of the IC assays with the immunofluorescence studies of the cutaneous vessel walls of the same patients showed agreement between the results of the C1q-BA and deposition of IgG and the results of the a-IgA-Inh BA and IgA deposition. The class of immunoglobulin in conglutinin-binding IC did not correspond as well with the immunoglobulins in vessel walls. This study shows that certain clinical features of allergic vasculitis are related to the composition of the IC in the circulation and in the vessel wall. PMID:7438561

  6. Reversible Aggregation of Albumin

    NASA Astrophysics Data System (ADS)

    Colby, Ralph H.; Oates, Katherine M. N.; Krause, Wendy E.; Jones, Ronald L.

    2004-03-01

    We explore the interactions in synovial fluid involving the polyelectrolyte sodium hyaluronate (NaHA) and plasma proteins in their native state (albumin and globulins). Rheological measurements on synovial fluid show it to be highly viscoelastic and also rheopectic (stress increases with time in steady shear). Equilibrium dialysis confirms the findings of Ogston and Dubin that there is no association between NaHA and albumin at physiological pH and salt. What we find instead is a reversible aggregation of albumin, with an association energy of order 3kT and commensurate association lifetime of order microseconds. Certain anti-inflammatory drugs are shown to prevent this reversible aggregation. The implications of these findings for synovial fluid and blood rheology are discussed.

  7. Tracking protein aggregate interactions

    PubMed Central

    Bartz, Jason C; Nilsson, K Peter R

    2011-01-01

    Amyloid fibrils share a structural motif consisting of highly ordered β-sheets aligned perpendicular to the fibril axis.1, 2 At each fibril end, β-sheets provide a template for recruiting and converting monomers.3 Different amyloid fibrils often co-occur in the same individual, yet whether a protein aggregate aids or inhibits the assembly of a heterologous protein is unclear. In prion disease, diverse prion aggregate structures, known as strains, are thought to be the basis of disparate disease phenotypes in the same species expressing identical prion protein sequences.4–7 Here we explore the interactions reported to occur when two distinct prion strains occur together in the central nervous system. PMID:21597336

  8. Rapid method to detect rubella immunoglobulin M and immunoglobulin A antibodies.

    PubMed Central

    Schmitz, H; Shimizu, H; Kampa, D; Doerr, H W

    1975-01-01

    Immunoglobulin (Ig) G was removed from serum specimens by precipitation with gamma chain-specific anti-human IgG of rabbit origin. The remaining rubella virus-specific IgM (and IgA) antibodies were then detected by the rubella hemagglutination-inhibition test. This procedure has proven to be as reliable as estimations carried out with IgM fractions separated on a sucrose density gradient. PMID:1176596

  9. Zooplankton Aggregations Near Sills

    DTIC Science & Technology

    2003-09-30

    frequency echo-sounder system. This data were supplemented with multi-net (BIONESS) trawls, bongo nets, and otter trawls (operated by D. Mackas and group...side. The general composition of the zooplankton aggregations can be deduced from the relative levels of the three echo-sounder frequencies; krill ...Nov. 20th, 2002. Krill layer is evident at 66 – 90 m, coincident with BIONESS trawl through the region. 3 Figure 2 shows a comparison between

  10. Serum immunoglobulin profile in normal Kashmiri adults.

    PubMed

    Bhat, G A; Mubarik, M; Bhat, M Y

    1995-01-01

    Serum levels of the immunoglobulins IgG, IgA and IgM were estimated in 102 apparently healthy Kashmiri adults in the age group of 16-60 years, using single radial immunodiffusion method of Mancini et al. The mean serum levels of IgG, IgA and IgM were observed to be 1289.19 +/- 234.9, 216.18 +/- 50.70 and 118.97 +/- 41.88 respectively. No significant difference in the mean serum levels was observed between the two sexes as such, but IgM showed a significant increase in females in the age group of 16-30 years. IgA showed a significant increase with age, with no such increase in case of IgG and IgM.

  11. Disodium cromoglycate inhibits production of immunoglobulin E.

    PubMed

    Seo, S B; Park, S J; Park, S T; Cho, C C; Park, B H; Lee, S J; Kim, H M; Kajiuchi, T; Shin, T Y

    2001-05-01

    Disodium cromoglycate (DSCG) has been shown to inhibit the release of mediators from mast cells. In the present study, the effect of DSCG on active anaphylactic reaction was studied in mice. DSCG dose-dependently inhibited the active systemic anaphylactic reaction and serum immunoglobulin (Ig)E production induced by immunization with ovalbumin, Bordetella pertussis toxin and aluminum hydroxide gel. DSCG strongly inhibited IL-4-dependent IgE production by lipopolysaccharide-stimulated murine whole spleen cells. In the case of U266 human IgE-bearing B cells, DSCG also showed an inhibitory effect on the IgE production. These results suggest that DSCG has an anti-anaphylactic activity by inhibition of IgE production from B cells.

  12. Immunoglobulins in tear in trachoma patients.

    PubMed Central

    Sen, D. K.; Sarin, G. S.; Saha, K.

    1977-01-01

    Tear immunoglobulin concentrations have been measured in 100 healthy people and 62 patients in different stages of trachoma. In healthy people the average IgA level was 27-8 mg/100 ml. There was no significant difference in the IgA level in various age groups and between the sexes. IgG was detected in 92 samples, and it was less than 1 mg/100 ml. IgM in tears was detected in only one sample. IgD was not detected in any specimen. In tracoma cases, the mean IgA level was found to be significantly lower (22-0 mg/100 ml) than in healthy people. There was no significant difference in IgA level between different stages of trachoma, IgG, IgD, and IgM could not be detected in any sample from the trachoma cases. PMID:856248

  13. 7th International Immunoglobulin Conference: Immunodeficiencies

    PubMed Central

    Schmidt, R E; Ochs, H D

    2014-01-01

    Awareness of the challenges involved in diagnosing and treating a heterogeneous group of immunodeficiency disorders is growing. The improvements in neonatal screening offer new methods to ensure that primary immunodeficiencies (PIDs) are diagnosed as early as possible, enabling accurate treatment and the prevention of life-threatening infections and other complications. Additionally, the need to individualize patient therapy in order to optimize both clinical outcomes and quality-of-life is obvious and is exemplified by the ability to switch between intravenous and subcutaneous immunoglobulin administration offering flexible treatment regimens. However, further research is crucial in order to determine the optimal treatment for secondary immunodeficiencies, and to gain greater understanding of the underlying causes of PIDs, including common variable immunodeficiency. The information relating to the growth of patient registries is encouraging, with approximately 25 000 patients with PIDs included in the two registries discussed. Registries such as this are vital for future research, as well as providing an educational resource. PMID:25546748

  14. Immunoglobulins and the X-chromosome.

    PubMed

    Rhodes, K; Markham, R L; Maxwell, P M; Monk-Jones, M E

    1969-08-23

    Serum levels of immunoglobulins (Ig) G, M, and A were determined in 28 women with an additional X-chromosome (XXX), and in equal numbers of age-matched normal women and men. Mean IgM levels were found to be highest in the XXX group, intermediate in normal women, and lowest in men; these differences were statistically significant. Mean IgM values obtained from seven XXY and three XXXY cases were almost identical with those of normal women and XXX women respectively. No such sex linkage was observed for IgA and IgG levels. These results support the suggestion that the serum level of IgM is related to the number of X chromosomes present.

  15. 7th International Immunoglobulin Conference: Immunomodulation

    PubMed Central

    Danieli, M G; Shoenfeld, Y

    2014-01-01

    Rheumatoid arthritis (RA) is a debilitating autoimmune disease that is usually treated aggressively to slow the rate of joint destruction. The therapeutic strategy used at the French centre, described here, is to use the non-biological disease-modifying drug, methotrexate, as first-line therapy and to add biological agents as second-line treatment. The two other autoimmune diseases discussed in this session were immunobullous skin diseases, and secondary recurrent miscarriage (RM). In the former conditions, low levels of pathogenic autoantibodies can be achieved with adjuvant intravenous immunoglobulin (IVIg) therapy, usually in combination with an immunosuppressant. Secondary RM has an autoimmune basis, as shown by high tumour necrosis factor (TNF)-α levels and specific human leucocyte antigen (HLA) polymorphisms. Although the mechanism is not yet known, IVIg may also be an effective treatment, despite the generally low doses used in published studies. PMID:25546788

  16. Structural repertoire of immunoglobulin λ light chains.

    PubMed

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

    2011-05-01

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

  17. Intravenous immunoglobulin in pediatrics: A review

    PubMed Central

    Prasad, A.N.; Chaudhary, Sanjay

    2013-01-01

    There has been a rapid expansion of the use of intravenous immunoglobulin (IVIG) for an ever-growing number of conditions. IVIG is used at a ‘replacement dose’ (400–600 mg/kg/month) in antibody deficiencies and is used at a high dose (2 g/kg) as an ‘immunomodulatory’ agent in an increasing number of immune and inflammatory disorders.1 The limitations for IVIG are the cost of the preparation and the need for intravenous infusions. Due to the cost, shortages and growing use of IVIG there have been attempts to develop evidence-based guidelines for the use of IVIG in a wide variety of immune disorders in children and neonates. This commentary provides the recommendations and recent publication regarding the use of IVIG in various conditions in children. PMID:25378784

  18. True hyponatremia secondary to intravenous immunoglobulin.

    PubMed

    Nguyen, Minhtri K; Rastogi, Anjay; Kurtz, Ira

    2006-06-01

    Hyponatremia is characterized as either "true hyponatremia," which represents a decrease in the Na(+) concentration in the water phase of plasma, or "pseudohyponatremia," which is due to an increased percentage of protein or lipid in plasma, with a normal plasma water Na(+) concentration ([Na(+)]). Pseudohyponatremia is a known complication of intravenous immunoglobulin (IVIG). Because IVIG has been reported to result in post-infusional hyperproteinemia, IVIG-induced hyponatremia has been attributed to pseudohyponatremia. In this case report, we demonstrate that IVIG therapy can result in true hyponatremia, resulting from sucrose-induced translocation of water from the intracellular compartment (ICF) to the extracellular compartment (ECF), as well as the infusion of a large volume of dilute fluid, in patients with an underlying defect in urinary free water excretion.

  19. Immunoglobulin Responses at the Mucosal Interface

    PubMed Central

    Chen, Kang; Chorny, Alejo

    2011-01-01

    Mucosal surfaces are colonized by large communities of commensal bacteria and represent the primary site of entry for pathogenic agents. To prevent microbial intrusion, mucosal B cells release large amounts of immunoglobulin (Ig) molecules through multiple follicular and extrafollicular pathways. IgA is the most abundant antibody isotype in mucosal secretions and owes its success in frontline immunity to its ability to undergo transcytosis across epithelial cells. In addition to translocating IgA onto the mucosal surface, epithelial cells educate the mucosal immune system as to the composition of the local microbiota and instruct B cells to initiate IgA responses that generate immune protection while preserving immune homeostasis. Here we review recent advances in our understanding of the cellular interactions and signaling pathways governing IgA production at mucosal surfaces and discuss new findings on the regulation and function of mucosal IgD, the most enigmatic isotype of our mucosal antibody repertoire. PMID:21219173

  20. Neonatally measured immunoglobulins and risk of autism.

    PubMed

    Grether, Judith K; Croen, Lisa A; Anderson, Meredith C; Nelson, Karin B; Yolken, Robert H

    2010-12-01

    Previous studies indicate that prenatal exposure to infections is a possible pathway through which autism spectrum disorders (ASD) could be initiated. We investigated whether immunoglobulin levels in archived specimens obtained from newborns subsequently diagnosed with ASD are different from levels in newborn specimens from controls. Children with ASD born in six California counties in 1994 were ascertained through records of the California Department of Developmental Services (DDS) and Kaiser Permanente; controls were randomly selected using birth certificates. Archived newborn blood specimens were obtained from the California Genetic Disease Screening Program (GDSP) for N = 213 cases and N = 265 controls and assayed to determine levels of total IgG, antigen-specific IgG to selected common pathogens, total IgM, total IgA, and C-reactive protein (CRP). We did not find measurable levels of total IgM or IgA in any neonate and measurable CRP was present in only a few. No antigen-specific IgG antibodies were elevated in cases compared to controls and total IgG levels were lower. In adjusted models, a 10-unit increase in total IgG yielded an OR = 0.72 (95% CI 0.56, 0.91); a significantly decreasing trend in risk of ASD was observed across increasing exposure quartiles of total IgG (P = 0.01). The finding of lower IgG in cases may indicate maternal immune dysfunction during gestation and/or impaired transplacental transfer of immunoglobulins. Further investigation of IgG levels in newborns and the mechanisms by which they might be associated with ASD are warranted. Copyright © 2010, International Society for Autism Research, Wiley Periodicals, Inc.

  1. 7(th) International Immunoglobulin Conference: Poster presentations.

    PubMed

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

    2014-12-01

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

  2. 7th International Immunoglobulin Conference: Poster Presentations

    PubMed Central

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

    2014-01-01

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

  3. Proteins aggregation and human diseases

    NASA Astrophysics Data System (ADS)

    Hu, Chin-Kun

    2015-04-01

    Many human diseases and the death of most supercentenarians are related to protein aggregation. Neurodegenerative diseases include Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), frontotemporallobar degeneration, etc. Such diseases are due to progressive loss of structure or function of neurons caused by protein aggregation. For example, AD is considered to be related to aggregation of Aβ40 (peptide with 40 amino acids) and Aβ42 (peptide with 42 amino acids) and HD is considered to be related to aggregation of polyQ (polyglutamine) peptides. In this paper, we briefly review our recent discovery of key factors for protein aggregation. We used a lattice model to study the aggregation rates of proteins and found that the probability for a protein sequence to appear in the conformation of the aggregated state can be used to determine the temperature at which proteins can aggregate most quickly. We used molecular dynamics and simple models of polymer chains to study relaxation and aggregation of proteins under various conditions and found that when the bending-angle dependent and torsion-angle dependent interactions are zero or very small, then protein chains tend to aggregate at lower temperatures. All atom models were used to identify a key peptide chain for the aggregation of insulin chains and to find that two polyQ chains prefer anti-parallel conformation. It is pointed out that in many cases, protein aggregation does not result from protein mis-folding. A potential drug from Chinese medicine was found for Alzheimer's disease.

  4. Interaction of Platelet Membrane Receptors with von Willebrand Factor, Ristocetin, and the Fc Region of Immunoglobulin G

    PubMed Central

    Moore, Anne; Ross, Gordon D.; Nachman, Ralph L.

    1978-01-01

    The agglutination of human platelets by ristocetin and von Willebrand factor was inhibited by aggregated immunoglobulin (Ig)G and by Fc fragments of IgG, but not by Fab, F(ab′)2 or pFc fragments of IgG. Because this inhibition occurred with formalin-fixed platelets as well as with normal platelets, a generalized aggregation of fluid membrane components by Fc fragments was not responsible for this inhibition of ristocetin and von Willebrand factor-induced agglutination. Reciprocal inhibition of platelet Fc receptors was produced by prior incubation of platelets with von Willebrand factor and ristocetin. Sucrose density gradient ultracentrifugation studies demonstrated that aggregated IgG did not form fluid-phase complexes with von Willebrand factor and ristocetin. Furthermore, passage of von Willebrand factor and ristocetin through a column of immobilized heat-aggregated IgG did not alter platelet agglutinating activity which indicates that aggregated IgG did not inactivate von Willebrand factor or ristocetin. Thus, it was likely that the IgG-mediated interference with platelet agglutination by ristocetin and von Willebrand factor did not occur in the fluid phase but at the platelet surface. These studies suggest that the platelet membrane Fc receptor may be either a part of, or sterically related to, the membrane glycoprotein I complex that interacts with von Willebrand factor, and that occupation of one of these surface components blocks the availability of the other. PMID:309473

  5. Surface immunoglobulin of guinea-pig leukaemic lymphocytes.

    PubMed Central

    Stevenson, G T; Eady, R P; Hough, D W; Jurd, R D; Stevenson, F K

    1975-01-01

    The surface immunoglobulin of the transplantable L2C leukaemia of strain 2 guinea-pigs has been investigated. The immunoglobulin is seen to be synthesized when the cells are maintained in culture, indicating its intrinsic origin. Immunolabelling of the cell surface and immunochemical study of the Fab released by limited surface proteolysis indicate the presence of immunoglobulin of class IgM. IgG and free light chains were not detected, and there is unlikely to be an appreciable amount of immunoglobulin of any other class. The amount of immunoglobulin present, in terms of 4-chain monomers, is approximately 100,000 molecules per cell. Its half-life, calculated from the rate of reappearance in vitro of surface Fab after proteolytic clearing, is approximately 5 hours. Immunoglobulin secreted into the environment appears to arise predominantly or entirely from the cell surface: there is no evidence of an appreciable export of immunoglobulin which does not have a surface phase. Papain at 0.06 mg/ml rapidly removes the surface Fab. Residual Fcmu can then be detected by immunofluorescence, suggesting that papain cleaves surface IgM at a hinge region with the molecule in situ on the membrane. The released Fab is only moderately susceptible to degradation by papain at the enzyme: substrate ratio prevailing. It has been possible to isolate it from the papain digest by immuno-adsorption, with a notional yield of 75 mug per 10-10 cells, and then to prepare antisera against it. PMID:48498

  6. Using Empirical Phase Diagrams to Understand the Role of Intramolecular Dynamics in Immunoglobulin G Stability

    PubMed Central

    Ramsey, Joshua D.; Gill, Michelle L.; Kamerzell, Tim J.; Price, E. Shane; Joshi, Sangeeta B.; Bishop, Steven M.; Oliver, Cynthia N.; Middaugh, C. Russell

    2013-01-01

    Understanding the relationship between protein dynamics and stability is of paramount importance to the fields of biology and pharmaceutics. Clarifying this relationship is complicated by the large amount of experimental data that must be generated and analyzed if motions that exist over the wide range of timescales are to be included. To address this issue, we propose an approach that utilizes a multidimensional vector-based empirical phase diagram (EPD) to analyze a set of dynamic results acquired across a temperature-pH perturbation plane. This approach is applied to a humanized immunoglobulin G1 (IgG1), a protein of major biological and pharmaceutical importance whose dynamic nature is linked to its multiple biological roles. Static and dynamic measurements are used to characterize the IgG and to construct both static and dynamic empirical phase diagrams. Between pH 5 and 8, a single, pH-dependent transition is observed that corresponds to thermal unfolding of the IgG. Under more acidic conditions, evidence exists for the formation of a more compact, aggregation resistant state of the immunoglobulin, known as A-form. The dynamics-based EPD presents a considerably more detailed pattern of apparent phase transitions over the temperature-pH plane. The utility and potential applications of this approach are discussed. PMID:19072858

  7. Using empirical phase diagrams to understand the role of intramolecular dynamics in immunoglobulin G stability.

    PubMed

    Ramsey, Joshua D; Gill, Michelle L; Kamerzell, Tim J; Price, E Shane; Joshi, Sangeeta B; Bishop, Steven M; Oliver, Cynthia N; Middaugh, C Russell

    2009-07-01

    Understanding the relationship between protein dynamics and stability is of paramount importance to the fields of biology and pharmaceutics. Clarifying this relationship is complicated by the large amount of experimental data that must be generated and analyzed if motions that exist over the wide range of timescales are to be included. To address this issue, we propose an approach that utilizes a multidimensional vector-based empirical phase diagram (EPD) to analyze a set of dynamic results acquired across a temperature-pH perturbation plane. This approach is applied to a humanized immunoglobulin G1 (IgG1), a protein of major biological and pharmaceutical importance whose dynamic nature is linked to its multiple biological roles. Static and dynamic measurements are used to characterize the IgG and to construct both static and dynamic EPDs. Between pH 5 and 8, a single, pH-dependent transition is observed that corresponds to thermal unfolding of the IgG. Under more acidic conditions, evidence exists for the formation of a more compact, aggregation resistant state of the immunoglobulin, known as A-form. The dynamics-based EPD presents a considerably more detailed pattern of apparent phase transitions over the temperature-pH plane. The utility and potential applications of this approach are discussed.

  8. Age-Dependent Protein Aggregation Initiates Amyloid-β Aggregation

    PubMed Central

    Groh, Nicole; Bühler, Anika; Huang, Chaolie; Li, Ka Wan; van Nierop, Pim; Smit, August B.; Fändrich, Marcus; Baumann, Frank; David, Della C.

    2017-01-01

    Aging is the most important risk factor for neurodegenerative diseases associated with pathological protein aggregation such as Alzheimer’s disease. Although aging is an important player, it remains unknown which molecular changes are relevant for disease initiation. Recently, it has become apparent that widespread protein aggregation is a common feature of aging. Indeed, several studies demonstrate that 100s of proteins become highly insoluble with age, in the absence of obvious disease processes. Yet it remains unclear how these misfolded proteins aggregating with age affect neurodegenerative diseases. Importantly, several of these aggregation-prone proteins are found as minor components in disease-associated hallmark aggregates such as amyloid-β plaques or neurofibrillary tangles. This co-localization raises the possibility that age-dependent protein aggregation directly contributes to pathological aggregation. Here, we show for the first time that highly insoluble proteins from aged Caenorhabditis elegans or aged mouse brains, but not from young individuals, can initiate amyloid-β aggregation in vitro. We tested the seeding potential at four different ages across the adult lifespan of C. elegans. Significantly, protein aggregates formed during the early stages of aging did not act as seeds for amyloid-β aggregation. Instead, we found that changes in protein aggregation occurring during middle-age initiated amyloid-β aggregation. Mass spectrometry analysis revealed several late-aggregating proteins that were previously identified as minor components of amyloid-β plaques and neurofibrillary tangles such as 14-3-3, Ubiquitin-like modifier-activating enzyme 1 and Lamin A/C, highlighting these as strong candidates for cross-seeding. Overall, we demonstrate that widespread protein misfolding and aggregation with age could be critical for the initiation of pathogenesis, and thus should be targeted by therapeutic strategies to alleviate neurodegenerative

  9. Effect of zinc supplementation on mycospecific immunoglobulins in tuberculosis patients.

    PubMed

    Chattopadhyay, Dipak Kumar; Maity, Chitta Ranjan; Nag, Debabrata

    2010-02-01

    The effect of zinc supplementation on the serum level of IgA, IgG, IgM mycospecific immunoglobulins in tuberculosis patients alongwith normal control and disease control subjects were studied. It was observed that with antituberculous drugs for one month (without zinc supplementation), the serum level of immunoglobulins in tuberculosis subjects although decreased significantly, but with zinc supplementation along with antituberculous drugs for one month the decrease in the level of immunoglobulins in serum was more significant. This may be attributed to the effect of zinc supplementation favouring the normal compartmentalisation state of iron and also to the immunomodulatory effect of zinc.

  10. A year in the life of the immunoglobulin superfamily.

    PubMed

    Williams, A F

    1987-01-01

    The superfamily of molecules with immunoglobulin-like domains has recently been gaining new members-largely on the basis of sequence homology. Here Alan Williams reviews this new work and reveals how the comparison of sequence patterns enables decisions on membership to be made. Accommodation of the new structures demands the provision of new categories, and forces the abandonment of the conserved disulphide bond as the last invariant characteristic of an immunoglobulin-type domain. They may, however, provide more dues to the origins and evolution of the immunoglobulin superfamily.

  11. [Replacement therapy with subcutaneous immunoglobulin in primary immunodeficiency in children].

    PubMed

    Pac, Małgorzata

    2011-06-01

    Primary antibody deficiency (PAD) is the most common form of primary immunodeficiency (PID), and presents up to 60-70% of PID. The hallmark of PAD are low antibody level and recurrent infections. Patients require life-long immunoglobulin replacement therapy. Now they can be treated either with intravenous (IVIG) or subcutaneous (SCIG) immunoglobulin. The last one is indicated in patients with unacceptable adverse reactions to the intravenous immunoglobulin preparations, with poor vein access or willing to improve the quality of their life. Several data and clinical trials proved that SCIG therapy is at least as safe and efficacious as IVIG to prevent infections in patients with PAD.

  12. Non-Arrhenius protein aggregation.

    PubMed

    Wang, Wei; Roberts, Christopher J

    2013-07-01

    Protein aggregation presents one of the key challenges in the development of protein biotherapeutics. It affects not only product quality but also potentially impacts safety, as protein aggregates have been shown to be linked with cytotoxicity and patient immunogenicity. Therefore, investigations of protein aggregation remain a major focus in pharmaceutical companies and academic institutions. Due to the complexity of the aggregation process and temperature-dependent conformational stability, temperature-induced protein aggregation is often non-Arrhenius over even relatively small temperature windows relevant for product development, and this makes low-temperature extrapolation difficult based simply on accelerated stability studies at high temperatures. This review discusses the non-Arrhenius nature of the temperature dependence of protein aggregation, explores possible causes, and considers inherent hurdles for accurately extrapolating aggregation rates from conventional industrial approaches for selecting accelerated conditions and from conventional or more advanced methods of analyzing the resulting rate data.

  13. Ultrastructure of acetylcholine receptor aggregates parallels mechanisms of aggregation

    PubMed Central

    Kunkel, Dennis D; Lee, Lara K; Stollberg, Jes

    2001-01-01

    Background Acetylcholine receptors become aggregated at the developing neuromuscular synapse shortly after contact by a motorneuron in one of the earliest manifestations of synaptic development. While a major physiological signal for receptor aggregation (agrin) is known, the mechanism(s) by which muscle cells respond to this and other stimuli have yet to be worked out in detail. The question of mechanism is addressed in the present study via a quantitative examination of ultrastructural receptor arrangement within aggregates. Results In receptor rich cell membranes resulting from stimulation by agrin or laminin, or in control membrane showing spontaneous receptor aggregation, receptors were found to be closer to neighboring receptors than would be expected at random. This indicates that aggregation proceeds heterogeneously: nanoaggregates, too small for detection in the light microscope, underlie developing microaggregates of receptors in all three cases. In contrast, the structural arrangement of receptors within nanoaggregates was found to depend on the aggregation stimulus. In laminin induced nanoaggregates receptors were found to be arranged in an unstructured manner, in contrast to the hexagonal array of about 10 nm spacing found for agrin induced nanoaggregates. Spontaneous aggregates displayed an intermediate amount of order, and this was found to be due to two distinct population of nanoaggregates. Conclusions The observations support earlier studies indicating that mechanisms by which agrin and laminin-1 induced receptor aggregates form are distinct and, for the first time, relate mechanisms underlying spontaneous aggregate formation to aggregate structure. PMID:11749670

  14. The influence of erythrocyte aggregation on induced platelet aggregation.

    PubMed

    Ott, C; Lardi, E; Schulzki, T; Reinhart, W H

    2010-01-01

    Red blood cells (RBCs) affect platelet aggregation in flowing blood (primary hemostasis). We tested the hypothesis that RBC aggregation could influence platelet aggregation. RBC aggregation was altered in vitro by: (i) changing plasma aggregatory properties with 3.7 g% dextran 40 (D40), 3.0 g% dextran 70 (D70) or 1.55 g% dextran 500 (D500); (ii) changing RBC aggregatory properties by incubating RBCs in 50 mU/ml neuraminidase for 60 min (reduction of the surface sialic acid content, thus reducing electrostatic repulsion) and subsequent RBC resuspension in platelet rich plasma (PRP) containing 1 g% dextran 70. RBC aggregation was assessed with the sedimentation rate (ESR). Platelet aggregation was measured: (i) in flowing whole blood with a platelet function analyzer PFA-100(R), which simulates in vivo conditions with RBCs flowing in the center and platelets along the wall, where they adhere to collagen and aggregate; and (ii) in a Chrono-log 700 Aggregometer, which measures changes of impedance by platelet aggregation in whole blood or changes in light transmission in PRP. We found that RBC aggregation increased with increasing molecular weight of dextran (ESR: 4 +/- 3 mm/h, 34 +/- 14 mm/h and 89 +/- 23 mm/hfor D40, D70 and D500, respectively, p < 0.0001) and with neuraminidase-treated RBCs (76 +/- 27 mm/h vs 27 +/- 8 mm/h, respectively, p < 0.0001). Platelet aggregation measured in whole blood under flow conditions (PFA-100) and without flow (Chronolog Aggregometer) was not affected by RBC aggregation. Our data suggest that RBC aggregation does not affect platelet aggregation in vitro and plays no role in primary hemostasis.

  15. Making Graphene Resist Aggregation

    NASA Astrophysics Data System (ADS)

    Luo, Jiayan

    Graphene-based sheets have stimulated great interest in many scientific disciplines and shown promise for wide potential applications. Among various ways of creating single atomic layer carbon sheets, a promising route for bulk production is to first chemically exfoliate graphite powders to graphene oxide (GO) sheets, followed by reduction to form chemically modified graphene (CMG). Due to the strong van der Waals attraction between graphene sheets, CMG tends to aggregate. The restacking of sheets is largely uncontrollable and irreversible, thus it reduces their processability and compromises properties such as accessible surface area. Strategies based on colloidal chemistry have been applied to keep CMG dispersed in solvents by introducing electrostatic repulsion to overcome the van der Waals attraction or adding spacers to increase the inter-sheet spacing. In this dissertation, two very different ideas that can prevent CMG aggregation without extensively modifying the material or introducing foreign spacer materials are introduced. The van der Waals potential decreases with reduced overlapping area between sheets. For CMG, reducing the lateral dimension from micrometer to nanometer scale should greatly enhance their colloidal stability with additional advantages of increased charge density and decreased probability to interact. The enhanced colloidal stability of GO and CMG nanocolloids makes them especially promising for spectroscopy based bio-sensing applications. For potential applications in a compact bulk solid form, the sheets were converted into paper-ball like structure using capillary compression in evaporating aerosol droplets. The crumpled graphene balls are stabilized by locally folded pi-pi stacked ridges, and do not unfold or collapse during common processing steps. They can tightly pack without greatly reducing the surface area. This form of graphene leads to scalable performance in energy storage. For example, planer sheets tend to aggregate and

  16. Structure of Viral Aggregates

    NASA Astrophysics Data System (ADS)

    Barr, Stephen; Luijten, Erik

    2010-03-01

    The aggregation of virus particles is a particular form of colloidal self-assembly, since viruses of a give type are monodisperse and have identical, anisotropic surface charge distributions. In small-angle X-ray scattering experiments, the Qbeta virus was found to organize in different crystal structures in the presence of divalent salt and non-adsorbing polymer. Since a simple isotropic potential cannot explain the occurrence of all observed phases, we employ computer simulations to investigate how the surface charge distribution affects the virus interactions. Using a detailed model of the virus particle, we find an asymmetric ion distribution around the virus which gives rise to the different phases observed.

  17. Shared epitopes of avian immunoglobulin light chains.

    PubMed

    Benčina, Mateja; Cizelj, Ivanka; Berčič, Rebeka Lucijana; Narat, Mojca; Benčina, Dušan; Dovč, Peter

    2014-04-15

    Like all jawed vertebrates, birds (Aves) also produce antibodies i.e. immunoglobulins (Igs) as a defence mechanism against pathogens. Their Igs are composed of two identical heavy (H) and light (L) chains which are of lambda isotype. The L chain consists of variable (VL), joining (JL) and constant (CL) region. Using enzyme immunoassays (EIA) and two monoclonal antibodies (mAbs) (3C10 and CH31) to chicken L chain, we analysed their cross-reactivity with sera from 33 avian species belonging to nine different orders. Among Galliformes tested, mAbs 3C10 and CH31 reacted with L chains of chicken, turkey, four genera of pheasants, tragopan and peafowl, but not with sera of grey partridge, quail and Japanese quail. Immunoglobulins of guinea-fowl reacted only with mAb 3C10. Both mAbs reacted also with the L chain of Eurasian griffon (order Falconiformes) and domestic sparrow (order Passeriformes). Sera from six other orders of Aves did not react with either of the two mAbs. EIA using mAbs 3C10 and CH31 enabled detection of antibodies to major avian pathogens in sera of chickens, turkeys, pheasants, peafowl, Eurasian griffon and guinea-fowl (only with mAb 3C10). The N-terminal amino acid sequence of pheasant L chain (19 residues) was identical to that of chicken. Sequences of genes encoding the L chain constant regions of pheasants, turkey and partridge were determined and deposited in the public database (GenBank accession numbers: FJ 649651, FJ 649652 and FJ 649653, respectively). Among them, amino acid sequence of pheasants is the most similar to that of chicken (97% similarity), whereas those of turkey and partridge have greater similarity to each other (89%) than to any other avian L chain sequence. The characteristic deletion of two amino acids which is present in the L chain constant region in Galliformes has been most likely introduced to their L chain after their divergence from Anseriformes.

  18. Rabbit anti-rabies immunoglobulins production and evaluation.

    PubMed

    Liu, Xinjian; Liu, Qiongqiong; Feng, Xiaomin; Tang, Qi; Wang, Zhongcan; Li, Suqing; Feng, Zhenqing; Zhu, Jin; Guan, Xiaohong

    2011-04-01

    Due to the disadvantages of human and equine rabies immunoglobulin, it is necessary to develop a substitute for HRIG and ERIG, especially for those people living in the developing countries. Because of higher affinity and lower immunogenicity of rabbit's immunoglobulins, anti-rabies immunoglobulins specific to rabies virus were produced in rabbits as a bioreactor, and had been characterized by ELISA, affinity assay, immunofluorescence assay (IFA), immunocytochemistry, rapid fluorescent focus inhibition test (RFFIT). ELISA, affinity assay and IFA showed that rabbit RIG (RRIG) bound specifically to rabies virions. RFFIT result showed that RRIG has neutralization activity. This result was confirmed in vivo in a Kunming mouse challenge model and the protection rate of the treatment with RRIG was higher (25%) than that offered by HRIG when mice were challenged with a lethal RV dose. Our results demonstrate that RRIG is safe and efficacious as a candidate drug to replace rabies immunoglobulin in post-exposure prophylaxis.

  19. Developing therapeutic immunoglobulins: European regulatory perspectives and implications.

    PubMed

    Kurz, Manfred

    2008-01-01

    Prepared from pooled human blood/plasma, therapeutic immunoglobulins contain the natural antibody spectrum of the entire donor population and mediate a range of therapeutic effects when administered to patients. They are particularly indicated for the prevention of serious and life-threatening infections in patients with immune systems failing to produce functional antibodies. Other than treatment of such rare primary immunodeficiencies (primary antibody deficiencies), therapeutic immunoglobulins are also used in certain inflammatory and autoimmune disorders, including immune thrombocytopenic purpura, Guillain Barré syndrome, and Kawasaki disease. The conditions for licensure of therapeutic immunoglobulins in the EU and the associated regulatory issues and procedures are reviewed. Regulatory expectations about the manufacture and control of immunoglobulins are highlighted and safety and efficacy requirements described. Although the main focus is on European pharmaceutical legislation, other applicable public information is considered.

  20. Taurine and platelet aggregation

    SciTech Connect

    Nauss-Karol, C.; VanderWende, C.; Gaut, Z.N.

    1986-03-01

    Taurine is a putative neurotransmitter or neuromodulator. The endogenous taurine concentration in human platelets, determined by amino acid analysis, is 15 ..mu..M/g. In spite of this high level, taurine is actively accumulated. Uptake is saturable, Na/sup +/ and temperature dependent, and suppressed by metabolic inhibitors, structural analogues, and several classes of centrally active substances. High, medium and low affinity transport processes have been characterized, and the platelet may represent a model system for taurine transport in the CNS. When platelets were incubated with /sup 14/C-taurine for 30 minutes, then resuspended in fresh medium and reincubated for one hour, essentially all of the taurine was retained within the cells. Taurine, at concentrations ranging from 10-1000 ..mu..M, had no effect on platelet aggregation induced by ADP or epinephrine. However, taurine may have a role in platelet aggregation since 35-39% of the taurine taken up by human platelets appears to be secreted during the release reaction induced by low concentrations of either epinephrine or ADP, respectively. This release phenomenon would imply that part of the taurine taken up is stored directly in the dense bodies of the platelet.

  1. [The use of human immunoglobulins--adverse reactions].

    PubMed

    Pituch-Noworolska, Anna; Błaut-Szlósarczyk, Anita; Zwonarz, Katarzyna

    2010-09-01

    The primary immunodeficiency, mainly humoral immunity, secondary immunodeficiency and autoimmune diseases are the indications for immunoglobulins substitution. The prolonged substitution in primary immunodeficiency includes regular intravenous infusion of immunoglobulins in 0.4-0.6 g/kg of body weight every 21-28 days. The purpose of such substitution is decrease of frequency and diminishes the clinical course of infections. The high-dose use of immunoglobulins (1-2 g/kg body weight) is preferred in autoimmune diseases based on suppressive and anti-inflammatory activity of immunoglobulins. The subcutaneous administration of immunoglobulins is an alternative to intravenous way, but the singular dose (0.1 g/kg body weight) is too low for suppressive and anti-inflammatory activity of immunoglobulins, so this substitution is indicated in primary immunodeficiency only. The adverse events of immunoglobulins differentiate because of time of occurrence and clinical character. The rapid symptoms occurred just after beginning of infusion and often present the clinical features of anaphylactoid reaction. During the infusion the occurring adverse symptoms are mild and the life-threatening situations are very rare. The next periods of typical adverse reaction are 24-48 hrs after infusion, 72 hrs and later. The mechanisms leading to adverse reaction to immunoglobulins are based on presence of IgG dimmers, stimulating high production of pro-inflammatory cytokines by immunocompetent cells. High level of cytokines is associated with high fever, chills, flu-like symptoms, feeling malaise and sick. The reaction of anti-IgA antibodies present in patient serum with IgA in immunoglobulins preparation is responsible for moderate and severe adverse clinical symptoms. The late adverse events present the symptoms of aseptic meningo-encephalitis. In case of adverse events the stopping of infusion, additions saline/ glucose infusion, anti-histaminic drugs of I and II generation and steroids

  2. Total remission of thymus carcinoma after treatment with intravenous immunoglobulin.

    PubMed

    Murie-Fernández, Manuel; Gurpide, Alfonso; de la Cruz, Susana; de Castro, Purificación

    2006-09-01

    We report the case of a 42 year-old woman with myasthenia gravis associated with a malignant thymoma. Despite surgery, chemotherapy and radiotherapy, the thymoma showed soft tissues, pleural and mediastinic progression. Unexpectedly, a complete remission of the thymoma was confirmed by FDG-PET after four cycles of immunoglobulins, administered as treatment for a myasthenic crisis. To our knowledge this is the first case report of complete remission of a malignant thymoma with immunoglobulin therapy.

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    2015-01-01

    Multiple subcutaneous immunoglobulin (SCIG) products are available to treat primary antibody deficiency (PAD). The efficacy and tolerability of 16% SCIG (Vivaglobin®) was compared with 20% SCIG (Hizentra®) in PAD subjects. The study was a prospective, single-centre, open-label study of PAD subjects transitioning Vivaglobin to equivalent Hizentra doses, rounded to the nearest vial size. Comparisons included immunoglobulin (Ig)G levels; tetanus, varicella and Streptococcus pneumoniae titres; adverse events (AEs), annual infection rate and quality of life during 8 weeks of Vivaglobin and 24 weeks of Hizentra. Thirty-two subjects (aged 2–75 years) participated. Rounding to the nearest Hizentra vial size resulted in a 12·8% (± 2·9%) increase in SCIG dose. Median immunoglobulin (Ig)G level following 8 weeks of Vivaglobin was similar to 24 weeks of Hizentra (1050 versus 1035 mg/dl, respectively; P = 0·77). Both products had similar protective titres to tetanus, varicella and serotypes of S. pneumoniae, which were variable but well above protective levels. After 12 weeks of Hizentra, subjects reported fewer local site reactions compared with Vivaglobin. Switching products resulted in increased systemic AEs in some subjects but, overall, not significantly higher than during Vivaglobin treatment. Average infusion time decreased from 104·7 min (3·3 sites) with Vivaglobin to 70·7 min (2·2 sites) with Hizentra (P = 0·0005). Acute serious bacterial infections were similar. Treatment satisfaction was superior with Hizentra. Hizentra and Vivaglobin have similar pharmacokinetics and efficacy. Although transition to a different SCIG product initially increased AEs, Hizentra is well tolerated and can be infused more rapidly and with fewer sites compared to Vivaglobin. PMID:25761372

  5. IMMUNOGLOBULIN SYNTHESIS AND SECRETION, III. INCORPORATION OF GLUCOSAMINE INTO IMMUNOGLOBULIN ON POLYRIBOSOMES*

    PubMed Central

    Sherr, Charles J.; Uhr, Jonathan W.

    1969-01-01

    Mouse myeloma cells were pulse-labeled in vitro with 3H-D-glucosamine and 14C-L-leucine. Analysis on sucrose gradients revealed incorporation of both isotopes into polyribosomes and release of most of such radioactivity after treatment of labeled cells in vitro with puromycin. A mixing experiment excluded the in vitro binding to unlabeled polyribosomes of 3H-glucosamine in labeled post-ribosomal material. Polyribosomes labeled with 3H-glucosamine were precipitated with antiserum specific for mouse immunoglobulin. By chromatography and gel filtration, the precipitable radioactivity was shown to be glucosamine covalently bound to heavy and light chains. PMID:5263020

  6. Immunoglobulin isotypes in Atlantic salmon, Salmo salar.

    PubMed

    Hordvik, Ivar

    2015-02-27

    There are three major immunoglobulin (Ig) isotypes in salmonid fish: IgM, IgD and IgT, defined by the heavy chains μ, δ and τ, respectively. As a result of whole genome duplication in the ancestor of the salmonid fish family, Atlantic salmon (Salmo salar) possess two highly similar Ig heavy chain gene complexes (A and B), comprising two μ genes, two δ genes, three intact τ genes and five τ pseudogenes. The μA and μB genes correspond to two distinct sub-populations of serum IgM. The IgM-B sub-variant has a characteristic extra cysteine near the C-terminal part of the heavy chain and exhibits a higher degree of polymer disulfide cross-linking compared to IgM-A. The IgM-B:IgM-A ratio in serum is typically 60:40, but skewed ratios are also observed. The IgT isotype appears to be specialized to mucosal immune responses in salmonid fish. The concentration of IgT in serum is 100 to 1000 times lower than IgM. Secreted forms of IgD have been detected in rainbow trout, but not yet in Atlantic salmon.

  7. Immunoglobulin A nephropathy complicating pulmonary tuberculosis.

    PubMed

    De Siati, L; Paroli, M; Ferri, C; Muda, A O; Bruno, G; Barnaba, V

    1999-10-01

    A 31-year-old man who presented with smear- and culture-negative pulmonary tuberculosis had associated macroscopic hematuria, elevation of serum creatinine and immunoglobulin A (IgA) levels, overt proteinuria, and peripheral edema. Renal biopsy revealed focal mesangial proliferation with IgA deposits, and a diagnosis of IgA nephropathy was made. The patient received treatment with isoniazide and rifampin. After 4 months, pulmonary lesions were almost completely healed, and a significant improvement of creatinine clearance with normalization of serum creatinine and IgA levels and disappearance of proteinuria were observed. Treatment with isoniazide and rifampin was discontinued after 6 months, without reappearance of either pulmonary or renal symptoms. Two years after the diagnosis of IgA nephropathy, the patient is in good general condition. Serum creatinine and IgA levels are normal, proteinuria is absent, and there is neither macrohematuria nor microhematuria. These findings suggest that IgA nephropathy may be a consequence of tuberculosis, possibly due to an abnormal IgA-mediated immune response against Mycobacterium tuberculosis with formation of nephrotoxic immune complexes.

  8. Immunological studies of an atypical (myeloma) immunoglobulin

    PubMed Central

    Johansson, S. G. O.; Bennich, H.

    1967-01-01

    An 8S myeloma component, isolated from serum of a patient with myelomatosis is described, which appears to have no antigenic determinants in common with human, α-, δ-, γ- or μ-polypeptide chains as revealed by immuno-electrophoresis and Ouchterlony gel diffusion analysis. The myeloma protein migrates in the fast γ-region on electrophoresis at pH 8.6 and has an elution volume on Sephadex G-200 similar to that of 6.5S IgA. The isolated myeloma component has an approximate molecular weight of 200,000 and a total carbohydrate content of 10.7 per cent. Reduction with β-mercaptoethanol and acid dissociation yields light polypeptide chains of Type L and a carbohydrate-rich component, in the ratio of 1:4. Antisera specific to determinants on the heavy chains of the myeloma protein showed no reaction with the immunoglobulins A, D, G or M. Instead unique determinants were found on the heavy polypeptide chains. ImagesFIG. 3FIG. 1FIG. 7FIG. 9FIG. 10 PMID:4168094

  9. Autoantibodies and immunoglobulins in collagenous colitis.

    PubMed Central

    Bohr, J; Tysk, C; Yang, P; Danielsson, D; Järnerot, G

    1996-01-01

    BACKGROUND: The aetiology and pathogenesis of collagenous colitis are unknown. Autoimmunity has been suggested, but no serological findings have supported such a theory. AIMS AND METHODS: Serum from 38 collagenous colitis patients and 38 matched healthy controls was analysed for autoantibodies--that is, antinuclear antibodies, antineutrophil cytoplasmic antibodies, smooth muscle and mitochondrial antibodies, rheumatoid factor and antibodies to thyroglobulin and microsomal antigen, together with antibodies to endomysium, gliadin, and cardiolipin. The serum values of IgA, IgG, IgM, and IgG-subclasses, and complement factors C3 and C4 were also determined. RESULTS: In patients with collagenous colitis the mean value of IgM was significantly increased 2.5 g/l (95% CI; 1.9, 3.2) compared with 1.4 g/l (95% CI; 1.2, 1.7) in controls (p = 0.002). Antinuclear antibodies occurred in nine of 38 patients compared with three of 38 controls, this difference was not statistically significant (p = 0.11). The results of all other immunoglobulins, complement factors, and specific antibodies showed no statistical difference between patients and controls. CONCLUSIONS: No firm evidence for an autoimmune genesis in collagenous colitis is found in this study, although the findings of a positive ANA-titre in some patients and an increased IgM level might give some support for this hypothesis. PMID:8881813

  10. Clinical applications of intravenous immunoglobulins in neurology.

    PubMed

    Hughes, R A C; Dalakas, M C; Cornblath, D R; Latov, N; Weksler, M E; Relkin, N

    2009-12-01

    Intravenous immunoglobulin (IVIg) is used increasingly in the management of patients with neurological conditions. The efficacy and safety of IVIg treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain-Barré syndrome (GBS) have been established clearly in randomized controlled trials and summarized in Cochrane systematic reviews. However, questions remain regarding the dose, timing and duration of IVIg treatment in both disorders. Reports about successful IVIg treatment in other neurological conditions exist, but its use remains investigational. IVIg has been shown to be efficacious as second-line therapy in patients with dermatomyositis and suggested to be of benefit in some patients with polymyositis. In patients with inclusion body myositis, IVIg was not shown to be effective. IVIg is also a treatment option in exacerbations of myasthenia gravis. Studies with IVIg in patients with Alzheimer's disease have reported increased plasma anti-Abeta antibody titres associated with decreased Abeta peptide levels in the cerebrospinal fluid following IVIg treatment. These changes at the molecular level were accompanied by improved cognitive function, and large-scale randomized trials are under way.

  11. Clinical applications of intravenous immunoglobulins in neurology

    PubMed Central

    Hughes, R A C; Dalakas, M C; Cornblath, D R; Latov, N; Weksler, M E; Relkin, N

    2009-01-01

    Intravenous immunoglobulin (IVIg) is used increasingly in the management of patients with neurological conditions. The efficacy and safety of IVIg treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain–Barré syndrome (GBS) have been established clearly in randomized controlled trials and summarized in Cochrane systematic reviews. However, questions remain regarding the dose, timing and duration of IVIg treatment in both disorders. Reports about successful IVIg treatment in other neurological conditions exist, but its use remains investigational. IVIg has been shown to be efficacious as second-line therapy in patients with dermatomyositis and suggested to be of benefit in some patients with polymyositis. In patients with inclusion body myositis, IVIg was not shown to be effective. IVIg is also a treatment option in exacerbations of myasthenia gravis. Studies with IVIg in patients with Alzheimer's disease have reported increased plasma anti-Aβ antibody titres associated with decreased Aβ peptide levels in the cerebrospinal fluid following IVIg treatment. These changes at the molecular level were accompanied by improved cognitive function, and large-scale randomized trials are under way. PMID:19883422

  12. Cytomegalovirus Immunoglobulin After Thoracic Transplantation: An Overview.

    PubMed

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

    2016-03-01

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

  13. 7th International Immunoglobulin Conference: Immunodeficiencies

    PubMed Central

    Schmidt, R E; Ochs, H D

    2014-01-01

    Most primary immunodeficiency disorders (PID) are the result of single gene defects. Based on this fact, more than 240 different entities have been identified. Those PIDs with predominant antibody deficiency are treated with immunoglobulin (Ig) replacement therapy. This review focuses on the diagnosis, clinical characteristics and treatment of patients suffering from PID, or secondary immunodeficiency disorders (SID) caused, for instance, by irradiation, immunosuppressive drugs or thymectomy. Common variable immunodeficiency (CVID) is the most commonly diagnosed and least understood form of PID, with a heterogeneous range of symptoms and genotypes, requiring individualized treatment plans. This includes adjusting the dose and treatment interval, administrating Ig by intravenous or subcutaneous injection by either pump or push, and finally deciding which treatment options are best for a given patient. Ig therapy can also be used to treat immunodeficiencies resulting from lymphoproliferative and autoimmune diseases or immunosuppression following organ transplantation; however, there is an urgent need for research in this field. Accurate and early diagnosis of PID is important to ensure that optimal treatment is started early to maintain the patient's health. Detailed patient registries have been established to increase awareness of PID, as well as provide a valuable resource for further research. PMID:25546741

  14. Immunoglobulin light chains, glycosaminoglycans and amyloid.

    SciTech Connect

    Stevens, F. J.; Kisilevsky, R.; Biosciences Division; Queen's Univ.

    2000-03-01

    Immunoglobulin light chains are the precursor proteins for fibrils that are formed during primary amyloidosis and in amyloidosis associated with multiple myeloma. As found for the approximately 20 currently described forms of focal, localized, or systemic amyloidoses, light chain-related fibrils extracted from physiological deposits are invariably associated with glycosaminoglycans, predominantly heparan sulfate. Other amyloid-related proteins are either structurally normal, such as g2-microglobulin and islet amyloid polypeptide, fragments of normal proteins such as serum amyloid A protein or the precursor protein of the g peptide involved in Alzheimer's disease, or are inherited forms of single amino acid variants of a normal protein such as found in the familial forms of amyloid associated with transthyretin. In contrast, the primary structures of light chains involved in fibril formation exhibit extensive mutational diversity rendering some proteins highly amyloidogenic and others non-pathological. The interactions between light chains and glycosaminoglycans are also affected by amino acid variation and may influence the clinical course of disease by enhancing fibril stability and contributing to resistance to protease degradation. Relatively little is currently known about the mechanisms by which glycosaminoglycans interact with light chains and light-chain fibrils. It is probable that future studies of this uniquely diverse family of proteins will continue o shed light on the processes of amyloidosis, and contribute as well to a greater understanding of the normal physiological roles of glycosaminoglycans.

  15. Dermatomyosite et panniculite: place des immunoglobulines

    PubMed Central

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

    2016-01-01

    La panniculite est une maladie inflammatoire du tissu adipeux sous-cutané rarement associée à la dermatomyosite. Elle peut survenir avant, après ou en même temps que l'atteinte musculaire. Dans la plupart des cas, l’évolution de la panniculite et des autres atteintes de la dermatomyosite est favorable sous traitement corticoïde et/ou immunosuppresseur. Nous rapportons le cas d'une patiente âgée de 48 ans ayant présenté des lésions de panniculite précédant de 2 mois les signes musculaires. L'atteinte cutanée était résistante au traitement corticoïde associés aux immunosuppresseurs ce qui a nécessité le recours au traitement par Immunoglobulines polyvalentes permettant ainsi une amélioration à la fois de l'atteinte cutanée et musculaire. PMID:27516827

  16. [Determination of serum immunoglobulins in asthmatic patients].

    PubMed

    Cabrera Jiménez, M; Valdés Sánchez, A F; Argüelles Sobrino, D; Gómez Echevarría, A H; Lastra Alfonso, G

    1989-01-01

    One hundred eighty one asthmatic patients were evaluated at the Allergy Consultation in Hermanos Ameijeiras Clinical Surgical Hospital. A case history was made for each of the patients, where the family background and personal history of allergy was collected; possible precipitating factors (such as inhalable, food, infectious, irritant, as well as climate factors) and physical and respiratory examinations. Serum immunoglobulin tests (by means of the ultramicroanalitic system (SUMA) and the rest of Igs: IgA, IgG, IgM by means of Mancini's simple radial immunodifusion method were made. Total eosinophil count was made to all of the patients in the study as well as serial studies of the faces. An increase in the IgE and IgM figures was found in asthmatic patients related to individual controls, and in relation to the normal figures for the adult population in our country. IgA and IgG determinations were normal both in the asthmatic and control groups, related to the standard figures.

  17. Immunoglobulin A: magic bullet or Trojan horse?

    PubMed

    Heineke, Marieke H; van Egmond, Marjolein

    2017-02-01

    Neutrophils participate in the first line of defense by executing several killing mechanisms, including phagocytosis, degranulation and the release of neutrophil extracellular traps. Additionally, they can orchestrate the adaptive immune system by secreting cytokines and chemokines. Opsonization with antibodies aids in the recognition of pathogens, via binding to Fc receptors on the neutrophil surface. Immunoglobulin A (IgA) is the most abundant antibody at mucosal sites and has multiple functions in homeostasis and immunity. Neutrophils and IgA can interact via the IgA Fc receptor Fc?RI (CD89), leading to pro- or anti-inflammatory responses. The aim of this review is to give a concise overview of the interplay between IgA, Fc?RI and neutrophils and to explore potential therapies for autoimmune diseases and cancer. Crosslinking of FcαRI by IgA-immune complexes yields potent neutrophil activation and pro-inflammatory effector functions, including the recruitment of neutrophils. This can lead to neutrophil accumulation and tissue destruction during IgA-autoantibody mediated diseases. Conversely, for cancer treatment, the myriad of powerful neutrophil effector functions after targeting FcαRI may contribute to effective immunotherapy. By interfering with or actively promoting the interaction between IgA and FcαRI, therapies for multiple maladies could be developed. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

  18. Immunoglobulin class-switch recombination deficiencies.

    PubMed

    Durandy, Anne; Kracker, Sven

    2012-07-30

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

  19. Immunoglobulin: production, mechanisms of action and formulations

    PubMed Central

    Novaretti, Marcia Cristina Zago; Dinardo, Carla Luana

    2011-01-01

    Human immunoglobulin (Ig) began to be applied in the clinical practice with the treatment of primary immunodeficiencies. Quickly, applications of Ig increased, as its anti-inflammatory and immunomodulatory functions were elucidated. Currently, Ig is the most commonly used blood product. Ig is obtained by processing plasma; methods, in particular, techniques to reduce plasma viral loads have been evolving over the years and include: pasteurization, solvent/ detergent treatment, caprylic acid treatment and nanofiltration. These methods contribute to increased safety and quality of blood products. The mechanisms of action of Ig not only involve the blockade of Fc receptors of phagocytes, but also control complement pathways, idiotype-anti-idiotype dimer formation, blockage of superantigen binding to T cells, inhibition of dendritic cells and stimulation of regulatory T cells (Tregs). There are several formulations of Ig available, each one with its own peculiar characteristics. In Brazil, there is stringent legislation regulating the quality of Ig. Only Ig products that completely fulfill the quality control criteria are released for use. These standards involve different tests from visual inspection to determination of anti-complementary activity. This paper will further review the history and current status of Ig, including its production and mechanisms of action. The formulations available in Brazil and also the criteria of quality control currently applied will be presented. PMID:23049343

  20. Holographic characterization of protein aggregates

    NASA Astrophysics Data System (ADS)

    Wang, Chen; Zhong, Xiao; Ruffner, David; Stutt, Alexandra; Philips, Laura; Ward, Michael; Grier, David

    Holographic characterization directly measures the size distribution of subvisible protein aggregates in suspension and offers insights into their morphology. Based on holographic video microscopy, this analytical technique records and interprets holograms of individual aggregates in protein solutions as they flow down a microfluidic channel, without requiring labeling or other exceptional sample preparation. The hologram of an individual protein aggregate is analyzed in real time with the Lorenz-Mie theory of light scattering to measure that aggregate's size and optical properties. Detecting, counting and characterizing subvisible aggregates proceeds fast enough for time-resolved studies, and lends itself to tracking trends in protein aggregation arising from changing environmental factors. No other analytical technique provides such a wealth of particle-resolved characterization data in situ. Holographic characterization promises accelerated development of therapeutic protein formulations, improved process control during manufacturing, and streamlined quality assurance during storage and at the point of use. Mrsec and MRI program of the NSF, Spheryx Inc.

  1. Solving Transportation Problems via Aggregation,

    DTIC Science & Technology

    1984-07-01

    AD-A144 219 SOLVING TRANSPORTATION PROBLEMS VIA AGGREGATION (U) i/l GEORGIA INST OF TECH ATLANTA PRODUCTION AND DISTRIBUTION RESEARCH CENTER R W...10 July 1984 SOLVING TRANSPORTATION PROBLEMS VIA AGGREGATION by" 4 Richard W. Taylort C. M. Shettytt PDRC 84-10 DTIC E L - TE~ School of Business...c UoaOO48--17 Rpouto spritein whol or pr for ny prpos of he U S. overment Abstract Solving Transportation Problems Via Aggregation 0

  2. Aggregation dynamics of rigid polyelectrolytes

    NASA Astrophysics Data System (ADS)

    Tom, Anvy Moly; Rajesh, R.; Vemparala, Satyavani

    2016-01-01

    Similarly charged polyelectrolytes are known to attract each other and aggregate into bundles when the charge density of the polymers exceeds a critical value that depends on the valency of the counterions. The dynamics of aggregation of such rigid polyelectrolytes are studied using large scale molecular dynamics simulations. We find that the morphology of the aggregates depends on the value of the charge density of the polymers. For values close to the critical value, the shape of the aggregates is cylindrical with height equal to the length of a single polyelectrolyte chain. However, for larger values of charge, the linear extent of the aggregates increases as more and more polymers aggregate. In both the cases, we show that the number of aggregates decrease with time as power laws with exponents that are not numerically distinguishable from each other and are independent of charge density of the polymers, valency of the counterions, density, and length of the polyelectrolyte chain. We model the aggregation dynamics using the Smoluchowski coagulation equation with kernels determined from the molecular dynamics simulations and justify the numerically obtained value of the exponent. Our results suggest that once counterions condense, effective interactions between polyelectrolyte chains short-ranged and the aggregation of polyelectrolytes are diffusion-limited.

  3. Fractal structure of asphaltene aggregates.

    PubMed

    Rahmani, Nazmul H G; Dabros, Tadeusz; Masliyah, Jacob H

    2005-05-15

    A photographic technique coupled with image analysis was used to measure the size and fractal dimension of asphaltene aggregates formed in toluene-heptane solvent mixtures. First, asphaltene aggregates were examined in a Couette device and the fractal-like aggregate structures were quantified using boundary fractal dimension. The evolution of the floc structure with time was monitored. The relative rates of shear-induced aggregation and fragmentation/restructuring determine the steady-state floc structure. The average floc structure became more compact or more organized as the floc size distribution attained steady state. Moreover, the higher the shear rate is, the more compact the floc structure is at steady state. Second, the fractal dimensions of asphaltene aggregates were also determined in a free-settling test. The experimentally determined terminal settling velocities and characteristic lengths of the aggregates were utilized to estimate the 2D and 3D fractal dimensions. The size-density fractal dimension (D(3)) of the asphaltene aggregates was estimated to be in the range from 1.06 to 1.41. This relatively low fractal dimension suggests that the asphaltene aggregates are highly porous and very tenuous. The aggregates have a structure with extremely low space-filling capacity.

  4. Peptide Aggregation in Finite Systems

    PubMed Central

    Singh, Gurpreet; Brovchenko, Ivan; Oleinikova, Alla; Winter, Roland

    2008-01-01

    Universal features of the peptide aggregation process suggest a common mechanism, with a first-order phase transition in aqueous solutions of the peptides being the driving force. Small system sizes strongly affect the stability of the minor phase in the two-phase region. We show manifestations of this effect in aqueous solutions of fragments of the islet amyloid polypeptide, using computer simulation methods and invoking various approaches in characterizing clustering and aggregate formation. These systems with peptide concentrations deeply inside the immiscibility region show two distinct stable states, which interchange with time: one state contains a peptide aggregate; and the other state has an aggregate that is noticeably dissolved. The first state is relevant for macroscopic systems, whereas the second one is artificial. At a fixed concentration, the occurrence probability of the aggregate state vanishes upon decreasing the system size, thus indicating the necessity to apply a finite size-scaling for meaningful studies of peptide aggregation by simulations. The effect observed may be one of the factors responsible for the difference between intracellular and extracellular aggregation and fibrillization of polypeptides. The finite size of biological cells or their compartments may be playing a decisive role in hampering intracellular aggregation of highly insoluble amyloidogenic proteins, whereas aggregation is unavoidable in the extracellular space at the same peptide concentration. PMID:18621830

  5. Molecular Aggregates in Cryogenic Solutions.

    DTIC Science & Technology

    1981-07-07

    of aggregates from solutions of monomers. Rapid deposition into a precooled sample cell is required to generate an aggregate solution. Such a solution...U AU-A11b 490 COLORAO0 STATE UNIV FORT COLLINS DEPT OF CHEMISTRY F/G 20/8 MOLECULAR AGGREGATES IN CRYOGENIC SOLUTIONS.CU) JUL 81 M W SCHAUER- J LEE...MOLECULAR AGGREGATES IN CRYOGENIC SOLUTIONS by M.W. Schauer, J. Lee, and E.R. Bernstein Prepared for Publication in The Journal of Chemical Physics

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

    PubMed Central

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

    1996-01-01

    All immunoglobulins and T-cell receptors throughout phylogeny share regions of highly conserved amino acid sequence. To identify possible primitive immunoglobulins and immunoglobulin-like molecules, we utilized 3' RACE (rapid amplification of cDNA ends) and a highly conserved constant region consensus amino acid sequence to isolate a new immunoglobulin class from the sandbar shark Carcharhinus plumbeus. The immunoglobulin, termed IgW, in its secreted form consists of 782 amino acids and is expressed in both the thymus and the spleen. The molecule overall most closely resembles mu chains of the skate and human and a new putative antigen binding molecule isolated from the nurse shark (NAR). The full-length IgW chain has a variable region resembling human and shark heavy-chain (VH) sequences and a novel joining segment containing the WGXGT motif characteristic of H chains. However, unlike any other H-chain-type molecule, it contains six constant (C) domains. The first C domain contains the cysteine residue characteristic of C mu1 that would allow dimerization with a light (L) chain. The fourth and sixth domains also contain comparable cysteines that would enable dimerization with other H chains or homodimerization. Comparison of the sequences of IgW V and C domains shows homology greater than that found in comparisons among VH and C mu or VL, or CL thereby suggesting that IgW may retain features of the primordial immunoglobulin in evolution. Images Fig. 1 Fig. 3 PMID:8622930

  7. The new generation of liquid intravenous immunoglobulin formulations in patient care: a comparison of intravenous immunoglobulins.

    PubMed

    Stein, Mark R

    2010-09-01

    Intravenous immunoglobulin (IGIV) replacement therapy is the standard of care for primary immunodeficiencies with impaired humoral immunity. It is also the immunomodulatory therapy of choice for some types of neuroimmunologic and autoimmune hematologic disorders and for immunomodulation in bone marrow and some solid organ transplants. Currently available IGIV products include older lyophilized formulations, 5% liquid products, and newer, liquid, ready-to-use, 10% formulations. Differences in the formulations, manufacturing processes, excipients, pH, and other physicochemical properties of IGIV products may affect their clinical efficacy and tolerability. Among at-risk patients, the possibility of serious complications such as renal insufficiency, heart failure, thrombotic events, and immunological reactions may be increased if an IGIV formulation has sugar as a stabilizer, has high sodium or immunoglobulin A (IgA) content, or is hyperosmolar. The 10% liquid formulations may offer advantages because of their lower IgA concentrations, optimal pH, glycine or proline stabilizers, low sodium content, and lower osmolality. Liquid formulations are more convenient for patients and health care providers due to shorter infusion times and easier preparation and administration.

  8. The Analysis of the Human High Affinity IgE Receptor FceRIa from Multiple Crystal Forms

    SciTech Connect

    Garman, S.C.; Sechi, S.; Kinet, J.-P.; Jardetzky, T.S.

    2010-03-05

    We have solved the structure of the human high affinity IgE receptor, Fc{var_epsilon}RI{alpha}, in six different crystal forms, showing the structure in 15 different chemical environments. This database of structures shows no change in the overall shape of the molecule, as the angle between domains 1 and 2 (D1 and D2) varies little across the ensemble. However, the receptor has local conformational variability in the C' strand of D2 and in the BC loop of D1. In every crystal form, a residue inserts between tryptophan residues 87 and 110, mimicking the position of a proline from the IgE ligand. The different crystal forms reveal a distribution of carbohydrates lining the front and back surfaces of the structure. An analysis of crystal contacts in the different forms indicates regions where the molecule interacts with other proteins, and reveals a potential new binding site distal to the IgE binding site. The results of this study point to new directions for the design of molecules to inhibit the interaction of Fc{var_epsilon}RI{alpha} with its natural ligand and thus to prevent a primary step in the allergic response.

  9. Up-regulation of prostaglandin E receptor EP2 and EP4 subtypes in rat synovial tissues with adjuvant arthritis

    PubMed Central

    Kurihara, Y; Endo, H; Akahoshi, T; Kondo, H

    2001-01-01

    To evaluate the role of the prostaglandin E receptor (EP) subtypes in the development of inflammatory synovitis, we examined EP subtype mRNA distribution in the synovial tissue of rats with adjuvant arthritis and the effect of selective EP agonists on cytokine production by cultured rat synovial cells. We used reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization to measure the level of EP subtype (EP1, EP2, EP3, and EP4) mRNA expression in synovial tissues and cultured synovial cells from the arthritic joints of rats. RT-PCR and ELISA were used to analyse the effects of two selective EP agonists on IL-6 production by cultured rat synovial cells. EP2 and EP4 mRNA expression in inflamed synovial tissues was up-regulated. EP2 and EP4 mRNA were co-expressed in synovial macrophages and fibroblasts in inflamed tissues. EP4 and EP2 agonists both inhibited IL-1-induced IL-6 production. Our results suggest that prostaglandin E2 regulates the functions of synovial macrophages and fibroblasts through EP2 and EP4, which are induced by inflammatory stimuli in rats with adjuvant arthritis. PMID:11207665

  10. Up-regulation of prostaglandin E receptor EP2 and EP4 subtypes in rat synovial tissues with adjuvant arthritis.

    PubMed

    Kurihara, Y; Endo, H; Akahoshi, T; Kondo, H

    2001-02-01

    To evaluate the role of the prostaglandin E receptor (EP) subtypes in the development of inflammatory synovitis, we examined EP subtype mRNA distribution in the synovial tissue of rats with adjuvant arthritis and the effect of selective EP agonists on cytokine production by cultured rat synovial cells. We used reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization to measure the level of EP subtype (EP1, EP2, EP3, and EP4) mRNA expression in synovial tissues and cultured synovial cells from the arthritic joints of rats. RT-PCR and ELISA were used to analyse the effects of two selective EP agonists on IL-6 production by cultured rat synovial cells. EP2 and EP4 mRNA expression in inflamed synovial tissues was up-regulated. EP2 and EP4 mRNA were co-expressed in synovial macrophages and fibroblasts in inflamed tissues. EP4 and EP2 agonists both inhibited IL-1-induced IL-6 production. Our results suggest that prostaglandin E2 regulates the functions of synovial macrophages and fibroblasts through EP2 and EP4, which are induced by inflammatory stimuli in rats with adjuvant arthritis.

  11. Prostaglandin E Receptor Subtype 4 Signaling in the Heart: Role in Ischemia/Reperfusion Injury and Cardiac Hypertrophy

    PubMed Central

    Cai, Yin; Tang, Eva Hoi Ching; Ma, Haichun

    2016-01-01

    Prostaglandin E2 (PGE2) is an endogenous lipid mediator, produced from the metabolism of arachidonic acids, upon the sequential actions of phospholipase A2, cyclooxygenases, and prostaglandin E synthases. The various biological functions governed by PGE2 are mediated through its four distinct prostaglandin E receptors (EPs), designated as EP1, EP2, EP3, and EP4, among which the EP4 receptor is the one most widely distributed in the heart. The availability of global or cardiac-specific EP4 knockout mice and the development of selective EP4 agonists/antagonists have provided substantial evidence to support the role of EP4 receptor in the heart. However, like any good drama, activation of PGE2-EP4 signaling exerts both protective and detrimental effects in the ischemic heart disease. Thus, the primary object of this review is to provide a comprehensive overview of the current progress of the PGE2-EP4 signaling in ischemic heart diseases, including cardiac hypertrophy and myocardial ischemia/reperfusion injury. A better understanding of PGE2-EP4 signaling should promote the development of more effective therapeutic approaches to treat the ischemic heart diseases without triggering unwanted side effects. PMID:27190998

  12. Dual regulation of mast cell degranulation through IgE receptor-mediated modulation of M₂-type pyruvate kinase.

    PubMed

    Zheng, Mei; Cho, Dong-Im; Le, Hang Thi; Cheon, Seung Hoon; Kim, Kyeong-Man

    2014-01-01

    It was reported that mast cell degranulation is inversely related to the enzymatic activity of M₂-type pyruvate kinase (M₂PK). This study shows that activation of high-affinity IgE receptor (FcεRI) evokes a sequential dual regulation of M₂PK, i.e., an immediate decrement followed by slow phase increment of enzymatic activities. Changes in the activities of M₂PK and mast cell degranulation showed similar time course after antigenic stimulation of FcεRI. The immediate inhibition of M₂PK involved tyrosine phosphorylation, and subsequently led to a cellular accumulation of glycolytic intermediates, including fructose 1,6-biphosphate (FBP), a feedforward activator of M₂PK. As the cellular levels of FBP were increased, both the enzymatic acitivity of M₂PK and mast cell degranulation slowly returned to near basal levels. A-Raf, when exogenously introduced into RBL-2H3 cells, phosphorylated M₂PK on the serine residues, elevated enzyme activities of M₂PK, and resulted in the inhibition of degranulation. These results suggest that dual regulation of M₂PK which involves the phosphorylation of M₂PK and accumulation of a feedforward activator of M₂PK plays important roles in the control of mast cell degranulation.

  13. Apolipoprotein E receptor 2 is involved in the thrombotic complications in a murine model of the antiphospholipid syndrome.

    PubMed

    Romay-Penabad, Zurina; Aguilar-Valenzuela, Renan; Urbanus, Rolf T; Derksen, Ronald H W M; Pennings, Maarten T T; Papalardo, Elizabeth; Shilagard, Tuya; Vargas, Gracie; Hwang, Yong; de Groot, Philip G; Pierangeli, Silvia S

    2011-01-27

    Antiphospholipid (aPL)/anti-β(2) glycoprotein I (anti-β(2)GPI) antibodies stimulates tissue factor (TF) expression within vasculature and in blood cells, thereby leading to increased thrombosis. Several cellular receptors have been proposed to mediate these effects, but no convincing evidence for the involvement of a specific one has been provided. We investigated the role of Apolipoprotein E receptor 2 (ApoER2') on the pathogenic effects of a patient-derived polyclonal aPL IgG preparation (IgG-APS), a murine anti-β(2)GPI monoclonal antibody (E7) and of a constructed dimeric β(2)GPI I (dimer), which in vitro mimics β(2)GPI-antibody immune complexes, using an animal model of thrombosis, and ApoER2-deficient (-/-) mice. In wild type mice, IgG-APS, E7 and the dimer increased thrombus formation, carotid artery TF activity as well as peritoneal macrophage TF activity/expression. Those pathogenic effects were significantly reduced in ApoER2 (-/-) mice. In addition, those effects induced by the IgG-APS, by E7 and by the dimer were inhibited by treatment of wild-type mice with soluble binding domain 1 of ApoER2 (sBD1). Altogether these data show that ApoER2 is involved in pathogenesis of antiphospholipids antibodies.

  14. Apolipoprotein E receptor 2 is involved in the thrombotic complications in a murine model of the antiphospholipid syndrome

    PubMed Central

    Romay-Penabad, Zurina; Aguilar-Valenzuela, Renan; Urbanus, Rolf T.; Derksen, Ronald H. W. M.; Pennings, Maarten T. T.; Papalardo, Elizabeth; Shilagard, Tuya; Vargas, Gracie; Hwang, Yong; de Groot, Philip G.

    2011-01-01

    Antiphospholipid (aPL)/anti-β2 glycoprotein I (anti-β2GPI) antibodies stimulates tissue factor (TF) expression within vasculature and in blood cells, thereby leading to increased thrombosis. Several cellular receptors have been proposed to mediate these effects, but no convincing evidence for the involvement of a specific one has been provided. We investigated the role of Apolipoprotein E receptor 2 (ApoER2′) on the pathogenic effects of a patient-derived polyclonal aPL IgG preparation (IgG-APS), a murine anti-β2GPI monoclonal antibody (E7) and of a constructed dimeric β2GPI I (dimer), which in vitro mimics β2GPI-antibody immune complexes, using an animal model of thrombosis, and ApoER2-deficient (−/−) mice. In wild type mice, IgG-APS, E7 and the dimer increased thrombus formation, carotid artery TF activity as well as peritoneal macrophage TF activity/expression. Those pathogenic effects were significantly reduced in ApoER2 (−/−) mice. In addition, those effects induced by the IgG-APS, by E7 and by the dimer were inhibited by treatment of wild-type mice with soluble binding domain 1 of ApoER2 (sBD1). Altogether these data show that ApoER2 is involved in pathogenesis of antiphospholipids antibodies. PMID:21119114

  15. Evaluation of cellular immune response during chronic schistosomiasis in humans by the leukocyte aggregation test and the leukocyte migration inhibition test.

    PubMed Central

    Rouveix, B; Derouin, F; Levacher, M

    1985-01-01

    Cellular immune response was evaluated in 31 patients with chronic Schistosoma haematobium and Schistosoma mansoni infections and in 15 healthy normal persons by using S. mansoni soluble worm and egg antigens. Although the leukocyte migration inhibition test demonstrated false-positive reactions, the specificity of the leukocyte aggregation test was confirmed by the negativity of all of the controls. Among the patients, only 10% were positive for the leukocyte aggregation test. This low cellular reactivity was in contrast to markedly elevated specific humoral response determined by an enzyme-linked immunosorbent assay for immunoglobulin G and paper allergosorbent test for immunoglobulin E with soluble worm antigen. These results confirm that the cellular immune reactivity to schistosome antigen as demonstrated by the leukocyte aggregation test is either minimal or absent in chronically infected patients. PMID:3988906

  16. Immunoglobulin VH determinants defined by monoclonal antibodies.

    PubMed

    Kubagawa, H; Mayumi, M; Kearney, J F; Cooper, M D

    1982-10-01

    Hybridoma clones secreting antibodies against common VH determinants were readily produced by fusion of cells from mice immunized with isolated V mu fragments of human immunoglobulins (Ig), but not with intact Ig molecules or isolated heavy chains. Four monoclonal antibodies to the V mu fragments of different IgM paraproteins were selected for analysis: MH-44 (mu kappa), GB-24 (mu kappa), NF-11 (gamma 1 kappa), and SA-44 (gamma 1 kappa). Each antibody reacted with the homologous V mu fragment, homologous mu chain, and normal gamma chains, but not with the intact IgM molecules, intact IgG, or isolated light chains, as determined by radioimmunoassay. The VH reaction spectra with a panel of myeloma heavy chains showed overlapping but distinctive patterns for the four antibodies. Each of the four monoclonal anti-VH antibodies appeared to react with a different "hidden" VH determinant that is not exposed on undenatured, intact Ig molecules and differs from conventional VH subgroup determinants. In immunofluorescence studies, the monoclonal anti-VH antibodies did not bind to surface Ig on viable B lymphocytes, but visibly stained subpopulations of fixed B lymphocytes, pre-B cells, and normal plasma cells. The mean frequencies of VH+ plasma cells were 30% (MH-44), 17% (GB-24), 13% (NF-11), and 3% (SA-44), and similar frequencies were obtained for the VH+ B cell subpopulations. While subpopulations of B cells could be identified at all stages in differentiation by immunofluorescence with the anti-VH antibodies, neither resting nor activated T cells expressed these VH determinants in detectable amounts.

  17. Immunoglobulin VH determinants defined by monoclonal antibodies

    PubMed Central

    1982-01-01

    Hybridoma clones secreting antibodies against common VH determinants were readily produced by fusion of cells from mice immunized with isolated V mu fragments of human immunoglobulins (Ig), but not with intact Ig molecules or isolated heavy chains. Four monoclonal antibodies to the V mu fragments of different IgM paraproteins were selected for analysis: MH-44 (mu kappa), GB-24 (mu kappa), NF-11 (gamma 1 kappa), and SA-44 (gamma 1 kappa). Each antibody reacted with the homologous V mu fragment, homologous mu chain, and normal gamma chains, but not with the intact IgM molecules, intact IgG, or isolated light chains, as determined by radioimmunoassay. The VH reaction spectra with a panel of myeloma heavy chains showed overlapping but distinctive patterns for the four antibodies. Each of the four monoclonal anti-VH antibodies appeared to react with a different "hidden" VH determinant that is not exposed on undenatured, intact Ig molecules and differs from conventional VH subgroup determinants. In immunofluorescence studies, the monoclonal anti-VH antibodies did not bind to surface Ig on viable B lymphocytes, but visibly stained subpopulations of fixed B lymphocytes, pre-B cells, and normal plasma cells. The mean frequencies of VH+ plasma cells were 30% (MH-44), 17% (GB-24), 13% (NF-11), and 3% (SA-44), and similar frequencies were obtained for the VH+ B cell subpopulations. While subpopulations of B cells could be identified at all stages in differentiation by immunofluorescence with the anti-VH antibodies, neither resting nor activated T cells expressed these VH determinants in detectable amounts. PMID:6185604

  18. Systemic sclerosis and prevalence of monoclonal immunoglobulin.

    PubMed

    Trad, Salim; Nosbaum, Audrey; Musset, Lucile; Ghillani-Dalbin, Pascale; Launay, David; Costedoat-Chalumeau, Nathalie; Saadoun, David; Cabane, Jean; Hachulla, Eric; Hanslik, Thomas; Frances, Camille

    2014-12-01

    The purpose of this study was to estimate the prevalence of monoclonal immunoglobulin (MIg) among patients with systemic sclerosis (SSc) according to the capillary electrophoresis or immunofixation method of detection and to search for any related clinical correlations. Retrospective multicenter comparison of capillary electrophoresis and immunofixation results in SSc patients and of the characteristics of patients with and without MIg. The study included 244 SSc patients (216 women and 28 men, mean age: 55±14 years). Median time since SSc diagnosis was 51 months [0-320]; disease was diffuse in 48% of cases. Ten percent of patients had cancer, including Waldenström macroglobulinemia (n=1) and multiple myeloma (n=3). Capillary electrophoresis showed a γ-globulin anomaly in 41% of cases, and immunofixation in 18%: MIg (13.5%) and restriction of heterogeneity (4.5%). Capillary electrophoresis failed to detect 60% of the 33 MIg patients. Measurable MIg concentrations were obtained from 7 patients. MIg patients were significantly older at SSc diagnosis than those without MIg (p=0.002), had a lower diffusing capacity (p=0.002), a higher prevalence of pulmonary hypertension and cancer (p=0.002) and were more frequently positive for anti-mitochondrial and anti-beta2-glycoprotein-I antibodies (p=0.03 and p=0.02, respectively). Multivariate analyses showed that only age at test [hazard ratio 1.03 (95% CI, 1.00-1.07, p=0.04)] and presence of cancer [hazard ratio 4.46 (95% CI, 1.6-12.4, p=0.004)] were associated with MIg. Immunofixation detected a high prevalence of MIg among SSc patients especially in patients aged 50-years or older. MIg was not detected by the standard capillary electrophoresis in 60% of cases and was significantly associated with cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. 7th International Immunoglobulin Conference: Immunomodulation

    PubMed Central

    Danieli, M G; Shoenfeld, Y

    2014-01-01

    Immunomodulation uses synthetic, natural and recombinant preparations to modify the immune response to a desired level, typically to treat specific autoimmune diseases, as will be discussed in this section. Rheumatoid arthritis (RA) is a common systemic autoimmune disease, affecting 1% of the population worldwide. Currently, a first-line disease-modifying therapy for RA is methotrexate; however, more than 40 monoclonal antibodies are in use or under investigation for the treatment of RA. This panoply of biological disease-modifying agents means that clinicians can make use of drugs with different mechanisms of action should one type become ineffective. In autoimmune pemphigus conditions, identification of pathogenic autoantibodies against intercellular cadherin desmoglein 1 and/or 3 antigens is one of the criteria for appropriate diagnosis. In pemphigoid conditions, autoantibodies are directed against bullous pemphigoid antigens BP230 and BP180, and in both types of immunobullous disease intravenous immunoglobulin (IVIg), as adjuvant therapy in combination with a cytotoxic drug, is effective in reducing autoantibody levels, disease severity and background steroid use. Further studies are required to establish the role of monoclonal antibodies in the treatment of autoimmune bullous disease. IVIg may also be effective in another at-risk population with autoimmune disease, namely secondary recurrent miscarriage (RM). However, the mechanism of action of IVIg in secondary RM is largely unknown, although levels of natural killer cell biomarkers, particularly CD56+, have been shown to decline after IVIg treatment [1-6]. Data from meta-analyses of heterogeneous placebo-controlled trials indicate that IVIg may be effective in secondary RM, but most trials to date have used immunomodulatory doses lower than those considered to be efficient in autoimmune disease. The results of a recently completed study may help to address this question. PMID:25546784

  20. Helicobacter pylori-related immunoglobulins in sarcoidosis.

    PubMed

    Herndon, Betty L; Vlach, Victoria; Dew, Michelle; Willsie, Sandra K

    2004-03-01

    The purpose of this study was to determine serum antibody titers against a common bacterial antigen, Helicobacter pylori (H. pylon), in subjects with sarcoidosis, comparing those titers to those present in a healthy population. With the approval of the Institutional Review Board of the University of Missouri-Kansas City, patients with sarcoidosis (pulmonary and extrapulmonary) who visited the Truman Medical Center-Hospital Hill pulmonary clinic were recruited to enter the study. A serum sample was frozen at -70 degrees C for later testing (n = 20). Specific information collected on subjects included corticosteroid use, use of histamine2 blockers and antacids, date of first diagnosis, and stage of sarcoidosis. Normal controls and demographically matched individuals who lacked pulmonary diseases, including sarcoidosis, were also recruited. Serum samples were processed as above. Antibody capture enzyme immunoassay was completed for H. pylori and urease antigens by serum dilution assay for each subject, from which titers for antigen-specific immunoglobulin (Ig)G and IgA were calculated. Nonspecific serum IgE was also measured. An increased incidence of high-titer IgG antibody directed against H. pylori antigens was found in subjects with sarcoidosis compared with controls. The sarcoidosis and control groups were significantly different with respect to IgG and IgA against H. pylori, both at p = .001. IgG directed against urease was also significantly different between sarcoidosis and control patients (p = .001), but IgA directed against urease was very low in all subjects and did not yield significant differences between groups. Specific H. pylori and urease IgG antibodies exceeded those expected in the population studied. The data suggest that in pulmonary sarcoidosis, the relationship of H. pylori and its products to sarcoid granuloma formation warrants further investigation.

  1. Immunoglobulin heavy chains in medaka (Oryzias latipes)

    PubMed Central

    2011-01-01

    Background Bony fish present an immunological system, which evolved independently from those of animals that migrated to land 400 million years ago. The publication of whole genome sequences and the availability of several cDNA libraries for medaka (Oryzias latipes) permitted us to perform a thorough analysis of immunoglobulin heavy chains present in this teleost. Results We identified IgM and IgD coding ESTs, mainly in spleen, kidney and gills using published cDNA libraries but we did not find any sequence that coded for IgT or other heavy chain isotypes described in fish. The IgM - ESTs corresponded with the secreted and membrane forms and surprisingly, the latter form only presented two constant heavy chain domains. This is the first time that this short form of membrane IgM is described in a teleost. It is different from that identified in Notothenioid teleost because it does not present the typical splicing pattern of membrane IgM. The identified IgD-ESTs only present membrane transcripts, with Cμ1 and five Cδ exons. Furthermore, there are ESTs with sequences that do not have any VH which disrupt open reading frames. A scan of the medaka genome using transcripts and genomic short reads resulted in five zones within a region on chromosome 8 with Cμ and Cδ exons. Some of these exons do not form part of antibodies and were at times interspersed, suggesting a recombination process between zones. An analysis of the ESTs confirmed that no antibodies are expressed from zone 3. Conclusions Our results suggest that the IGH locus duplication is very common among teleosts, wherein the existence of a recombination process explains the sequence homology between them. PMID:21676244

  2. Immunoglobulin negative follicle centre cell lymphoma.

    PubMed Central

    Gregg, E. O.; Al-Saffar, N.; Jones, D. B.; Wright, D. H.; Stevenson, F. K.; Smith, J. L.

    1984-01-01

    Immunoglobulin (Ig) could not be detected on the surface or in the cytoplasm of neoplastic cells from five cases of follicle centre cell lymphoma with centroblastic/centrocytic follicular histology when examined by immunohistology of frozen or wax embedded sections. Examination by fluorescein labelled antibodies of cells in suspensions prepared from the biopsies revealed a monotypic surface Ig positive population in one case and a surface or cytoplasmic Ig kappa:lambda light chain imbalance in a further two cases consistent with neoplastic B cell involvement: in all cases the proportion of cells failing to express Ig or T cell markers ranged from 24 to 75%. The monoclonal antibodies B1 (Pan B cell), FMC4 (HLA class II) and J5 (cALL antigen) stained the majority of cells in suspension with residual cells staining with UCHT1 or OKT11 (T cell monoclonal antibodies). In frozen sections, neoplastic follicular cells did not stain with UCHT1. However, in the one case tested these cells stained with the antibodies B1 and FMC4. In paraffin sections J chain could be demonstrated in the cytoplasm of three out of five cases. Cells from four cases were cultured in vitro for Ig production: two failed to produce Ig and monotypic light chains were the sole Ig product of the remaining two cases. The failure to express Ig by the majority of the neoplastic cells from the cases described in this report is at variance with the follicular histology of these neoplasms. Mechanisms responsible for this failure are discussed with reference to current models of B cell differentiation. Images Figure 1 PMID:6437429

  3. Hyaluronidase facilitated subcutaneous immunoglobulin in primary immunodeficiency

    PubMed Central

    Jolles, Stephen

    2013-01-01

    Immunoglobulin (Ig)-replacement therapy represents the mainstay of treatment for patients with primary antibody deficiency and is administered either intravenously (IVIg) or subcutaneously (SCIg). While hyaluronidase has been used in clinical practice for over 50 years, the development of a high-purity recombinant form of this enzyme (recombinant human hyaluronidase PH20) has recently enabled the study of repeated and more prolonged use of hyaluronidase in facilitating the delivery of SC medicines. It has been used in a wide range of clinical settings to give antibiotics, local anesthetics, insulin, morphine, fluid replacement, and larger molecules, such as antibodies. Hyaluronidase has been used to help overcome the limitations on the maximum volume that can be delivered into the SC space by enabling dispersion of SCIg and its absorption into lymphatics. The rate of facilitated SCIg (fSCIg) infusion is equivalent to that of IVIg, and the volume administered at a single site can be greater than 700 mL, a huge increase over conventional SCIg, at 20–40 mL. The use of fSCIg avoids the higher incidence of systemic side effects of IVIg, and it has higher bioavailability than SCIg. Data on the long-term safety of this approach are currently lacking, as fSCIg has only recently become available. fSCIg may help several areas of patient management in primary antibody deficiency, and the extent to which it may be used in future will depend on long-term safety data and cost–benefit analysis. PMID:27471693

  4. Quantitation of soluble aggregates in recombinant monoclonal antibody cell culture by pH-gradient protein A chromatography.

    PubMed

    Pan, Hai; Chen, Ken; Pulisic, Matt; Apostol, Izydor; Huang, Gang

    2009-05-15

    Monoclonal antibodies (mAbs) produced from mammalian cell culture may contain significant amounts of dimers and higher order aggregates. Quantitation of soluble aggregates in the cell culture is time-consuming and labor-intensive, usually involving a purification step to remove the impurities that interfere with the subsequent size exclusion chromatography (SEC) analysis. We have developed a novel pH-gradient protein A chromatography for rapid, non-size based separation of the aggregates in mAb cell culture samples. Our results demonstrate that this method has excellent correlation with SEC and can be applied to both human immunoglobulin gamma 1 (IgG1) and IgG2 antibodies. This approach can be useful in the quantitation of soluble aggregates in crude cell culture samples.

  5. Topics in Probabilistic Judgment Aggregation

    ERIC Educational Resources Information Center

    Wang, Guanchun

    2011-01-01

    This dissertation is a compilation of several studies that are united by their relevance to probabilistic judgment aggregation. In the face of complex and uncertain events, panels of judges are frequently consulted to provide probabilistic forecasts, and aggregation of such estimates in groups often yield better results than could have been made…

  6. Topics in Probabilistic Judgment Aggregation

    ERIC Educational Resources Information Center

    Wang, Guanchun

    2011-01-01

    This dissertation is a compilation of several studies that are united by their relevance to probabilistic judgment aggregation. In the face of complex and uncertain events, panels of judges are frequently consulted to provide probabilistic forecasts, and aggregation of such estimates in groups often yield better results than could have been made…

  7. Mineral of the month: aggregates

    USGS Publications Warehouse

    Tepordei, Valentin V.

    2005-01-01

    Natural aggregates, consisting of crushed stone, and sand and gravel, are a major contributor to economic health, and have an amazing variety of uses. Aggregates are among the most abundant mineral resources and are major basic raw materials used by construction, agriculture and other industries that employ complex chemical and metallurgical processes.

  8. Hsp70 and antifibrillogenic peptides promote degradation and inhibit intracellular aggregation of amyloidogenic light chains.

    SciTech Connect

    Dul, J. L.; Davis, D. P.; Williamson, E. K.; Stevens, F. J.; Argon, Y.; Univ. of Chicago

    2001-02-19

    In light chain (LC) amyloidosis an immunoglobulin LC assembles into fibrils that are deposited in various tissues. Little is known about how these fibrils form in vivo. We previously showed that a known amyloidogenic LC, SMA, can give rise to amyloid fibrils in vitro when a segment of one of its {beta} sheets undergoes a conformational change, exposing an Hsp70 binding site. To examine SMA aggregation in vivo, we expressed it and its wild-type counterpart, LEN, in COS cells. While LEN is rapidly oxidized and subsequently secreted, newly synthesized SMA remains in the reduced state. Most SMA molecules are dislocated out of the ER into the cytosol, where they are ubiquitinylated and degraded by proteasomes. A parallel pathway for molecules that are not degraded is condensation into perinuclear aggresomes that are surrounded by vimentin-containing intermediate filaments and are dependent upon intact microtubules. Inhibition of proteasome activity shifts the balance toward aggresome formation. Intracellular aggregation is decreased and targeting to proteasomes improved by overexpression of the cytosolic chaperone Hsp70. Importantly, transduction into the cell of an Hsp70 target peptide, derived from the LC sequence, also reduces aggresome formation and increases SMA degradation. These results demonstrate that an amyloidogenic LC can aggregate intracellularly despite the common presentation of extracellular aggregates, and that a similar molecular surface mediates both in vitro fibril formation and in vivo aggregation. Furthermore, rationally designed peptides can be used to suppress this aggregation and may provide a feasible therapeutic approach.

  9. Molecular aggregation of humic substances

    USGS Publications Warehouse

    Wershaw, R. L.

    1999-01-01

    Humic substances (HS) form molecular aggregates in solution and on mineral surfaces. Elucidation of the mechanism of formation of these aggregates is important for an understanding of the interactions of HS in soils arid natural waters. The HS are formed mainly by enzymatic depolymerization and oxidation of plant biopolymers. These reactions transform the aromatic and lipid plant components into amphiphilic molecules, that is, molecules that consist of separate hydrophobic (nonpolar) and hydrophilic (polar) parts. The nonpolar parts of the molecules are composed of relatively unaltered segments of plant polymers and the polar parts of carboxylic acid groups. These amphiphiles form membrane-like aggregates on mineral surfaces and micelle-like aggregates in solution. The exterior surfaces of these aggregates are hydrophilic, and the interiors constitute separate hydrophobic liquid-like phases.

  10. Imbibition kinetics of spherical aggregates

    NASA Astrophysics Data System (ADS)

    Hébraud, Pascal; Lootens, Didier; Debacker, Alban

    The imbibition kinetics of a millimeter-sized aggregate of 300 nm diameter colloidal particles by a wetting pure solvent is studied. Three successive regimes are observed : in the first one, the imbibition proceeds by compressing the air inside the aggregate. Then, the solvent stops when the pressure of the compressed air is equal to the Laplace pressure at the meniscus of the wetting solvent in the porous aggregate. The interface is pinned and the aggregate slowly degases, up to a point where the pressure of the entrapped air stops decreasing and is controlled by the Laplace pressure of small bubbles. Depending on the curvature of the bubble, the system may then be in an unstable state. The imbibition then starts again, but with an inner pressure in equilibrium with these bubbles. This last stage leads to the complete infiltration of the aggregate.

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

    PubMed

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

    2017-02-01

    We investigated, at diagnosis, the relationship between serum immunoglobulin G4 levels and the main characteristics of Graves' disease: hyperthyroidism severity, goiter size, presence of active Graves' ophthalmopathy, antithyroid antibodies status, and titer. This prospective study included 80 newly diagnosed Graves' disease patients. The main parameters measured at diagnosis: thyroid-stimulating hormone, free thyroxine, free triiodothyronine, total triiodothyronine, thyroglobulin, antithyroid peroxidase antibodies, anti-thyroglobulin antibodies, thyroid-stimulating hormone receptor antibodies, immunoglobulin G4. In Graves' disease patients, serum immunoglobulin G4 levels were higher than in general population (p = 0.028) and higher in men compared to women (p = 0.002). Only one female patient with intense hypoechoic goiter, high anti-thyroglobulin antibody, and antithyroid peroxidase antibody titers had an elevated serum immunoglobulin G4 level at diagnosis. Patients with immunoglobulin G4 levels above the 75th percentile (>237.52 mg/dl, N = 20) were younger at Graves' ophthalmopathy onset (p < 0.001), had higher antithyroid peroxidase antibody (p = 0.01), and anti-thyroglobulin antibody levels (p = 0.006) and required shorter duration of the first methimazole treatment cycle (p = 0.041) than patients with immunoglobulin G4 below the 75th percentile. At diagnosis, patients with immunoglobulin G4 levels above the 90th percentile (>286.28 mg/dl, N = 8) had lower total triiodothyronine values (p = 0.001) than patients with IgG below the 90th percentile. No significant correlations were found between smoking status (p = 0.58), goiter size (p = 0.50), the presence of ophthalmopathy (p = 0.42) or thyroid-stimulating hormone receptor antibody titers (p = 0.45) and the mean value of immunoglobulin G4 levels at diagnosis. Our data suggest that Graves' disease patients with elevated immunoglobulin G4 levels at

  12. Premature red blood cells have decreased aggregation and enhanced aggregability.

    PubMed

    Arbell, D; Orkin, B; Bar-Oz, B; Barshtein, G; Yedgar, S

    2008-06-01

    Preterm infants are highly susceptible to ischemic damage. This damage is most obvious in the brain, retina, and gastrointestinal tract. Studies focusing on the rheological properties of premature red blood cells (pRBCs) have consistently shown minimal or no RBC aggregation. Previously, measurements of pRBC aggregation kinetics indicated that specific plasma properties are responsible for the decreased RBC aggregation observed in the neonates, but that their specific RBC properties do not affect it. However, the strength of interaction in the pRBC aggregates as a function of medium composition has not been tested. In our previous research, we described clinically relevant parameters, that is, the aggregate resistance to disaggregation by flow. With the help of a cell flow property analyzer (CFA), we can monitor RBC aggregation by direct visualization of its dynamics during flow. We used the CFA to examine pRBC (from 9 premature babies) in the natural plasma and in PBS buffer supplemented with dextran (500 kDa) to distinguish between RBC intrinsic-cellular and plasma factors. pRBCs suspended in the native plasma showed minimal or no aggregation in comparison to normal adult RBC. When we transferred pRBCs from the same sample to the dextran solution, enhanced resistance to disaggregation by flow was apparent.

  13. [Critical considerations on the behavior of immunoglobulins in rheumatoid arthritis].

    PubMed

    Troise, W; Riccardi, L; Bulgarelli, G; Sesenna, G; Ambanelli, U

    1975-01-01

    Critical evaluation of immunoglobulins in Rheumatoid Arthritis. It has been studied the behavior of the serum and synovial immunoglobulins of 62 patients afftected arthritis reheumatoid in various clinic stages; the valued have been expressed in mg% and mg/g of proteins. The serum levels of the IgG and IgA are higher in the cases of R.A. than in normals. The synovial concentrations of the IgA and IgM are lower than the respective serum values, while the phenomenon is less evident for the IgG probably because the last are synthetised in the synovial means. It exists, however, a interdipendence between the concentration of the serum and synovial immunoglobulins. The concentrations of the immunoglobulines, both serum and synovial, are not in relation with the most usual humoral phlogosis-tests, as well as they are not correlable with the values of the naturals antiproteases and with some fractions of the complement (both of the classic and alternative pathway). The variations of the immunoglobulins are, in the R.A., aspecific and of different intensity therefore their determination is not proposable neither as test of measure of the phlogosis nor as index of disease.

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

    PubMed

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

    2016-02-01

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

  15. Evolutionary Genomics of Immunoglobulin-Encoding Loci in Vertebrates

    PubMed Central

    Das, Sabyasachi; Hirano, Masayuki; Tako, Rea; McCallister, Chelsea; Nikolaidis, Nikolas

    2012-01-01

    Immunoglobulins (or antibodies) are an essential element of the jawed vertebrate adaptive immune response system. These molecules have evolved over the past 500 million years and generated highly specialized proteins that recognize an extraordinarily large number of diverse substances, collectively known as antigens. During vertebrate evolution the diversification of the immunoglobulin-encoding loci resulted in differences in the genomic organization, gene content, and ratio of functional genes and pseudogenes. The tinkering process in the immunoglobulin-encoding loci often gave rise to lineage-specific characteristics that were formed by selection to increase species adaptation and fitness. Immunoglobulin loci and their encoded antibodies have been shaped repeatedly by contrasting evolutionary forces, either to conserve the prototypic structure and mechanism of action or to generate alternative and diversified structures and modes of function. Moreover, evolution favored the development of multiple mechanisms of primary and secondary antibody diversification, which are used by different species to effectively generate an almost infinite collection of diverse antibody types. This review summarizes our current knowledge on the genomics and evolution of the immunoglobulin-encoding loci and their protein products in jawed vertebrates. PMID:23024601

  16. The Production Processes and Biological Effects of Intravenous Immunoglobulin

    PubMed Central

    Barahona Afonso, Ana Filipa; João, Cristina Maria Pires

    2016-01-01

    Immunoglobulin is a highly diverse autologous molecule able to influence immunity in different physiological and diseased situations. Its effect may be visible both in terms of development and function of B and T lymphocytes. Polyclonal immunoglobulin may be used as therapy in many diseases in different circumstances such as primary and secondary hypogammaglobulinemia, recurrent infections, polyneuropathies, cancer, after allogeneic transplantation in the presence of infections and/or GVHD. However, recent studies have broadened the possible uses of polyclonal immunoglobulin showing that it can stimulate certain sub-populations of T cells with effects on T cell proliferation, survival and function in situations of lymphopenia. These results present a novel and considerable impact of intravenous immunoglobulin (IVIg) treatment in situations of severe lymphopenia, a situation that can occur in cancer patients after chemo and radiotherapy treatments. In this review paper the established and experimental role of polyclonal immunoglobulin will be presented and discussed as well as the manufacturing processes involved in their production. PMID:27005671

  17. Orthogonal flexible Rydberg aggregates

    NASA Astrophysics Data System (ADS)

    Leonhardt, K.; Wüster, S.; Rost, J. M.

    2016-02-01

    We study the link between atomic motion and exciton transport in flexible Rydberg aggregates, assemblies of highly excited light alkali-metal atoms, for which motion due to dipole-dipole interaction becomes relevant. In two one-dimensional atom chains crossing at a right angle adiabatic exciton transport is affected by a conical intersection of excitonic energy surfaces, which induces controllable nonadiabatic effects. A joint exciton-motion pulse that is initially governed by a single energy surface is coherently split into two modes after crossing the intersection. The modes induce strongly different atomic motion, leading to clear signatures of nonadiabatic effects in atomic density profiles. We have shown how this scenario can be exploited as an exciton switch, controlling direction and coherence properties of the joint pulse on the second of the chains [K. Leonhardt et al., Phys. Rev. Lett. 113, 223001 (2014), 10.1103/PhysRevLett.113.223001]. In this article we discuss the underlying complex dynamics in detail, characterize the switch, and derive our isotropic interaction model from a realistic anisotropic one with the addition of a magnetic bias field.

  18. Identification of a phage-encoded immunoglobulin-binding protein from invasive Neisseria meningitidis†

    PubMed Central

    Müller, Maike G.; Ing, Jessica Y.; Cheng, Mike Kai-Wick; Flitter, Becca A.; Moe, Gregory R.

    2013-01-01

    Immunoglobulin (Ig)-binding proteins are employed by a variety of organisms to evade the immune system. We now report for the first time that meningococcal strains from several capsular groups exhibit Ig-binding activity that is dependent on human serum factors. A protein mediating Ig binding was identified as T and B cell stimulating protein B (TspB) by immunoprecipitation and by mass spectroscopic analysis of tryptic peptides. Recombinant TspB and derivatives verified Ig binding, with a preference for human IgG2 Fc, and localized the IgG-binding region to a highly conserved subdomain of TspB. Antiserum produced in mice against the conserved subdomain, detected the presence of TspB on the cell surface by flow cytometry when bacteria were grown in the presence of human serum. By fluorescence microscopy, we observed formation of an extracellular matrix having characteristics of a biofilm containing TspB, human IgG, DNA, and large aggregates of bacteria. TspB is encoded by gene ORF6 in prophage DNA, which others have shown is associated with invasive meningococcal strains. Knocking out ORF6 genes eliminated IgG binding and formation of large bacterial aggregates in biofilm. Reintroduction of a wild-type ORF6 gene by phage transduction restored the phenotype. The results show that TspB mediated IgG binding and aggregate/biofilm formation triggered by factors in human serum. As has been observed for other Ig-binding proteins, the activities mediated by TspB may provide protection against immune responses, which is in accordance with the association of prophage DNA carrying ORF6 with invasive meningococcal strains. PMID:23926326

  19. Concurrent Drug-Induced Linear Immunoglobulin A Dermatosis and Immunoglobulin A Nephropathy.

    PubMed

    Kim, Ji Seok; Choi, Misoo; Nam, Chan Hee; Kim, Jee Young; Park, Byung Cheol; Kim, Myung Hwa; Hong, Seung Phil

    2015-06-01

    Diseases associated with immunoglobulin A (IgA) antibody include linear IgA dermatosis, IgA nephropathy, Celiac disease, Henoch-Schönlein purpura, etc. Although usually idiopathic, IgA antibody is occasionally induced by drugs (e.g., vancomycin, carbamazepine, ceftriaxone, and cyclosporine), malignancies, infections, and other causes. So far, only a few cases of IgA bullous dermatosis coexisting with IgA nephropathy have been reported. A 64-year-old female receiving intravenous ceftriaxone and metronidazole for liver abscess had purpuric macules and papules on her extremities. One week later, she had generalized edema and skin rash with bullae and was diagnosed with concurrent linear IgA dermatosis and IgA nephropathy. After steroid treatment, the skin lesion subsided within two weeks, and kidney function slowly returned to normal. As both diseases occurred after a common possible cause, we predict their pathogeneses are associated.

  20. Interference of immunoglobulins in two glucagon radioimmunoassays. [Blood donor and patient immunoglobulins

    SciTech Connect

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

    1982-05-01

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

  1. Immunoglobulin in health and disease. III. Immunoglobulins in the sera of patients with amoebiasis

    PubMed Central

    Dasgupta, A.

    1974-01-01

    The serum immunoglobulins IgG, IgA, IgM and IgE were determined together with indirect haemagglutination test in normal subjects and in patients with intestinal and extra-intestinal amoebiasis. The IgG level in intestinal amoebiasis was found to be significantly higher than that of extra-intestinal. Although in intestinal amoebiasis, the concentrations of IgE were comparatively higher than extra-intestinal group, the IgE levels in both groups of amoebiasis were seen to be much higher than that of the normal group. No significant difference was found in the IgA and IgM levels between the three groups of cases. Indirect haemagglutination test was positive in both intestinal and extra-intestinal amoebiasis, but negative in normal subjects. PMID:4377710

  2. Intravenous and subcutaneous immunoglobulin G replacement therapy.

    PubMed

    Bonilla, Francisco A

    2016-11-01

    Human polyclonal immunoglobulin G (IgG) for therapeutic use has been available for decades. This drug was developed for treatment of antibody deficiency (replacement therapy), although its use has expanded into many anti-inflammatory and immunomodulatory applications in recent years. This review focuses on IgG prescribing for replacement therapy. IgG for replacement is most often administered via the intravenous IgG (IVIG) or subcutaneous IgG (SCIG) routes. IVIG is usually administered every 34 weeks, and SCIG is usually administered weekly, although variations may be considered in all cases. Recently, a new product became available that uses hyaluronidase to facilitate absorption of large doses of SCIG less frequently (every 34 weeks, as with IVIG). There are important differences between the pharmacokinetics of these three routes of administration. IVIG therapy leads to high peaks and low troughs between infusions. IgG concentration fluctuates much less over time with SCIG. Hyaluronidase-facilitated SCIG is intermediate. SCIG may have lower bioavailability in comparison with IVIG and may require higher doses over time; this is not true for hyaluronidase SCIG. However, there are large variations in IgG half-life among individuals and with different products. Therefore, individualization of therapy is essential. Mild systemic flu-like adverse effects may affect up to 2025% of patients who receive IVIG, smaller fractions may experience more-severe symptoms, whereas anaphylaxis is exceedingly rare. General flu-like systemic adverse effects are minimal with SCIG (intermediate with hyaluronidase SCIG), but transient (24 hours), mild, local inflammatory symptoms at infusion sites are relatively common with both forms. Additional rare but important complications of IgG therapy include thrombotic events and hemolysis that can be seen at high doses with any route of administration. Renal adverse effects may occur with IVIG as well. The variety of IgG products and routes of

  3. Stress modulates intestinal secretory immunoglobulin A

    PubMed Central

    Campos-Rodríguez, Rafael; Godínez-Victoria, Marycarmen; Abarca-Rojano, Edgar; Pacheco-Yépez, Judith; Reyna-Garfias, Humberto; Barbosa-Cabrera, Reyna Elizabeth; Drago-Serrano, Maria Elisa

    2013-01-01

    Stress is a response of the central nervous system to environmental stimuli perceived as a threat to homeostasis. The stress response triggers the generation of neurotransmitters and hormones from the hypothalamus pituitary adrenal axis, sympathetic axis and brain gut axis, and in this way modulates the intestinal immune system. The effects of psychological stress on intestinal immunity have been investigated mostly with the restraint/immobilization rodent model, resulting in an up or down modulation of SIgA levels depending on the intensity and time of exposure to stress. SIgA is a protein complex formed by dimeric (dIgA) or polymeric IgA (pIgA) and the secretory component (SC), a peptide derived from the polymeric immunoglobulin receptor (pIgR). The latter receptor is a transmembrane protein expressed on the basolateral side of gut epithelial cells, where it uptakes dIgA or pIgA released by plasma cells in the lamina propria. As a result, the IgA-pIgR complex is formed and transported by vesicles to the apical side of epithelial cells. pIgR is then cleaved to release SIgA into the luminal secretions of gut. Down modulation of SIgA associated with stress can have negative repercussions on intestinal function and integrity. This can take the form of increased adhesion of pathogenic agents to the intestinal epithelium and/or an altered balance of inflammation leading to greater intestinal permeability. Most studies on the molecular and biochemical mechanisms involved in the stress response have focused on systemic immunity. The present review analyzes the impact of stress (mostly by restraint/immobilization, but also with mention of other models) on the generation of SIgA, pIgR and other humoral and cellular components involved in the intestinal immune response. Insights into these mechanisms could lead to better therapies for protecting against pathogenic agents and avoiding epithelial tissue damage by modulating intestinal inflammation. PMID:24348350

  4. Apolipoprotein E receptor-2 (ApoER2) mediates selenium uptake from selenoprotein P by the mouse testis.

    PubMed

    Olson, Gary E; Winfrey, Virginia P; Nagdas, Subir K; Hill, Kristina E; Burk, Raymond F

    2007-04-20

    Selenium is a micronutrient that is essential for the production of normal spermatozoa. The selenium-rich plasma protein selenoprotein P (Sepp1) is required for maintenance of testis selenium and for fertility of the male mouse. Sepp1 trafficking in the seminiferous epithelium was studied using conventional methods and mice with gene deletions. Immunocytochemistry demonstrated that Sepp1 is present in vesicle-like structures in the basal region of Sertoli cells, suggesting that the protein is taken up intact. Sepp1 affinity chromatography of a testicular extract followed by mass spectrometry-based identification of bound proteins identified apolipoprotein E receptor 2 (ApoER2) as a candidate testis Sepp1 receptor. In situ hybridization analysis identified Sertoli cells as the only cell type in the seminiferous epithelium with detectable ApoER2 expression. Testis selenium levels in apoER2(-/-) males were sharply reduced from those in apoER2(+/+) males and were comparable with the depressed levels found in Sepp1(-/-) males. However, liver selenium levels were unchanged by deletion of apoER2. Immunocytochemistry did not detect Sepp1 in the Sertoli cells of apoER2(-/-) males, consistent with a defect in the receptor-mediated Sepp1 uptake pathway. Phase contrast microscopy revealed identical sperm defects in apoER2(-/-) and Sepp1(-/-) mice. Co-immunoprecipitation analysis demonstrated an interaction of testis ApoER2 with Sepp1. These data demonstrate that Sertoli cell ApoER2 is a Sepp1 receptor and a component of the selenium delivery pathway to spermatogenic cells.

  5. Functionality of Immunoglobulin G and Immunoglobulin M Antibody Physisorbed on Cellulosic Films.

    PubMed

    Huang, Ziwei; Raghuwanshi, Vikram Singh; Garnier, Gil

    2017-01-01

    The functionality and aging mechanism of antibodies physisorbed onto cellulosic films was investigated. Blood grouping antibodies immunoglobulin G (IgG) and immunoglobulin M (IgM) were adsorbed onto smooth cellulose acetate (CAF) and regenerated cellulose (RCF) films. Cellulose films and adsorbed IgG layers were characterized at the air and liquid interface by X-ray and neutron reflectivity (NR), respectively. Cellulose film 208 Å thick (in air) swell to 386 Å once equilibrated in water. IgG adsorbs from solution onto cellulose as a partial layer 62 Å thick. IgG and IgM antibodies were adsorbed onto cellulose and cellulose acetate films, air dried, and aged at room temperature for periods up to 20 days. Antibody functionality and surface hydrophobicity were measured everyday with the size of red blood cell (RBC) agglutinates (using RBC specific to IgG/IgM) and the water droplet contact angle, respectively. The functionality of the aged IgG/IgM decreases faster if physisorbed on cellulose than on cellulose acetate and correlates to surface hydrophobicity. IgG physisorbed on RCF or CAF age better and remain functional longer than physisorbed IgM. We found a correlation between antibody stability and hydrogen bond formation ability of the system, evaluated from antibody carbonyl concentration and cellulosic surface hydroxyl concentration. Antibody physisorbs on cellulose by weak dipole forces and hydrogen bonds. Strong hydrogen bonding contributes to the physisorption of antibody on cellulose into a non-functional configuration in which the molecule relaxes by rotation of hydophobic groups toward the air interface.

  6. Properties and mechanisms of immunoglobulins for congenital cytomegalovirus disease.

    PubMed

    Parruti, Giustino; Polilli, Ennio; Ursini, Tamara; Tontodonati, Monica

    2013-12-01

    Immunoglobulins are one major component of adaptive immunity to external and resident microorganisms, evolving very early in phylogenesis. They help eukaryotes in controlling infections, mainly through their neutralizing activity, which quenches both the cytopathic and inflammatory potential of invading microorganisms. Cytomegalovirus (CMV)-related disease is generally blunted in seropositive subjects with conserved specific humoral responses. CMV-seropositive pregnant women, in accordance with such evidence, suffer little or no fetal damage when reexposed to CMV. Several seminal experiences and early experimental models confirmed that repeated infusions of immunoglobulins, either with hyperimmune or standard preparations, may help to reduce maternal-fetal CMV transmission, as well as to quench fetal disease upon transmission. This review focused on experimental evidence supporting the potential role of immunoglobulins as a tool to control fetal CMV-related disease in pregnant women.

  7. Immunoglobulin therapy in the treatment of multifocal motor neuropathy.

    PubMed

    Kumar, Aditya; Patwa, Huned S; Nowak, Richard J

    2017-04-15

    Multifocal motor neuropathy (MMN) is a chronic immune-mediated disorder leading to slowly progressive muscle weakness and wasting. Current treatments are aimed at modulating the immune system in order to avoid further decline and to maintain functional status. Intravenous immunoglobulin (IVIg) is widely used in the treatment of immune-mediated disorders and is the only treatment approved for MMN. While patients do remain stable with maintenance IVIg treatment, most patients will slowly deteriorate over many years. The use of subcutaneous immunoglobulin (ScIg) is also gaining acceptance in this disease. The amount of axonal loss and the number of years without immunoglobulin (Ig) treatment appear to be associated with the permanence of weakness. We summarize the key literature to date that supports Ig use in the treatment of MMN.

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

    PubMed

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

    2015-08-24

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

  9. FUNDAMENTAL DIFFERENCES BETWEEN NATURAL ANTIBODIES AND POLYREACTIVE IMMUNOGLOBULINS.

    PubMed

    Bobrovnik, S A; Demchenko, M A; Komisarenko, S V

    2015-01-01

    A problem of similarity and differences between so-called polyreactive immunoglobulins (PRIGs) and natural antibodies (NAbs), capable of cross-reacting with some structurally dissimilar antigens, has been considered. The analysis of mechanisms of an unspecific interaction between PRIGs or NAbs and antigens evidences for the fact that essential differences exist between these substances. These differences permit classifying the abovementioned substances as different types of immunoglobulin molecules. The major difference between PRIGs and NAbs may include both the mechanisms of the above mentioned immunoglobulin molecules binding to antigens and their interaction affinity, as well as an absolutely different influence of some low-molecular substances on the efficiency of the interaction with antigens. Relying on the obtained data it can be assumed that, since PRIGs and NAbs have fundamental differences, they may perform not only similar but also different functions of the immune system.

  10. The binding of immunoglobulin Fc to cationic proteins.

    PubMed Central

    Pambakian, S; Poston, R N

    1987-01-01

    The interaction of cationic proteins with IgG, IgA and IgM were investigated by solid phase radioimmunoassay. All these immunoglobulins showed avid binding, IgM giving the strongest reaction, followed by IgA and then IgG. Fc fragments of IgG gave binding, but F(ab')2 fragments from the three main Ig classes did not, showing that the Fc region is the active part of the molecule. The effects of changes of ionic strength and pH are compatible with the interaction being ionic, and are similar to those seen between immunoglobulins and both Clq and cationic ion exchange gels. The addition of other serum proteins resulted in marked inhibition of the interaction. These phenomena are likely to have fundamental significance for the understanding of interactions of immunoglobulins in vivo and in vitro. Images Fig. 6 PMID:3652520

  11. Quantitative levels of immunoglobulin E in advanced tuberculosis.

    PubMed

    Casterline, C L; Evans, R; Ward, G W

    1976-07-01

    Quantitative levels of immunoglobulin E (IgE) were determined in samples of sera obtained from 29 patients with proven moderate to far-advanced tuberculosis. The sensitive radioimmunoassay test for IgE was used. Statistical analysis of the results revealed no difference in IgE values as compared to a control group of normal sera. In contrast to other chronic pulmonary infections, such as bronchopulmonary aspergillosis, the IgE level in pulmonary tuberculous infection is of no diagnostic significance. Simultaneous determination of levels of immunoglobulins G, A, M, and D (IgG, IgA, IgM, IgD) in these same sera by radial immunodiffusion showed elevated IgG and lowered IgM levels in the tuberculous patients, confirming previous studies. The significance of these alterations in immunoglobulin levels is unclear and may represent a secondary phenomenon rather than a primary host response.

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

    PubMed Central

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

    2015-01-01

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

  13. Immunoglobulin molecules detection with nanopore sensors fabricated from glass tubes.

    PubMed

    Sha, Jingjie; Zhang, Lei; Liu, Lei; Bi, Kedong; Yi, Hong; Chen, Yunfei; Ni, Zhonghua

    2014-06-01

    Nanopores are increasingly utilized as tools for single molecule detection in biotechnology. Here, we report an improved fabrication process to make solid-state nanopores from glass tubes with the help of paraffin. Based on the physical footprint of the phase change of the paraffin, nanocavity is formed in the broken terminal after thermally compressing and pulling the glass capillary. Nanopores with the minimum diameter of 50 nm are fabricated. Different immunoglobulin molecules including IgG, IgA, IgM mixed in a 10 mM KCl solution are used to test the sensing capabilities of the glass-nanopore sensor. Various modulated ionic current modes were observed while the the three type immunoglobulin molecules translocate the nanopore because the molecules had different size and structure. Based on the difference in the duration time and amplitude of the transient electrical pulse signals, we are able to discriminate the three immunoglobulin molecules.

  14. Kinetics of Aggregation with Choice

    SciTech Connect

    Ben-Naim, Eli; Krapivsky, Paul

    2016-12-01

    Here we generalize the ordinary aggregation process to allow for choice. In ordinary aggregation, two random clusters merge and form a larger aggregate. In our implementation of choice, a target cluster and two candidate clusters are randomly selected and the target cluster merges with the larger of the two candidate clusters.We study the long-time asymptotic behavior and find that as in ordinary aggregation, the size density adheres to the standard scaling form. However, aggregation with choice exhibits a number of different features. First, the density of the smallest clusters exhibits anomalous scaling. Second, both the small-size and the large-size tails of the density are overpopulated, at the expense of the density of moderate-size clusters. Finally, we also study the complementary case where the smaller candidate cluster participates in the aggregation process and find an abundance of moderate clusters at the expense of small and large clusters. Additionally, we investigate aggregation processes with choice among multiple candidate clusters and a symmetric implementation where the choice is between two pairs of clusters.

  15. Kinetics of Aggregation with Choice

    DOE PAGES

    Ben-Naim, Eli; Krapivsky, Paul

    2016-12-01

    Here we generalize the ordinary aggregation process to allow for choice. In ordinary aggregation, two random clusters merge and form a larger aggregate. In our implementation of choice, a target cluster and two candidate clusters are randomly selected and the target cluster merges with the larger of the two candidate clusters.We study the long-time asymptotic behavior and find that as in ordinary aggregation, the size density adheres to the standard scaling form. However, aggregation with choice exhibits a number of different features. First, the density of the smallest clusters exhibits anomalous scaling. Second, both the small-size and the large-size tailsmore » of the density are overpopulated, at the expense of the density of moderate-size clusters. Finally, we also study the complementary case where the smaller candidate cluster participates in the aggregation process and find an abundance of moderate clusters at the expense of small and large clusters. Additionally, we investigate aggregation processes with choice among multiple candidate clusters and a symmetric implementation where the choice is between two pairs of clusters.« less

  16. Immunoglobulin M Nephropathy in a Patient with Wilson's Disease.

    PubMed

    Ul Abideen, Zain; Sajjad, Zoya; Haroon Khan, Asna; Mamoon, Nadira; Bilal, Muhammad; Mujtaba Quadri, Khaja Hameeduddin

    2016-12-13

    Immunoglobulin M nephropathy (IgMN) is characterized by the deposition of immunoglobulin M in a dominant distribution in the renal glomeruli. Primary immunoglobulin M nephropathy is diagnosed after consistent light microscopy (LM), immunofluorescence (IF), electron microscopy (EM) results, and exclusion of known systemic disorders causing immunoglobulin M deposition in the glomeruli. The secondary disease has been reported with a few conditions though it has never been reported with any primary disease of the liver. We report the case of an adolescent male patient who presented with nausea, vomiting, diarrhea, and worsening anasarca. He was found to have nephrotic-range proteinuria that did not respond to conventional corticosteroid treatment. He was subjected to a renal biopsy which revealed a diagnosis of immunoglobulin M nephropathy. His liver function tests were deranged and an ultrasound scan of the abdomen revealed a coarse irregular liver. Workup revealed elevated urine copper excretion and a low ceruloplasmin level. He was diagnosed as a case of Wilson's disease and started on penicillamine and pyridoxine. He was also started on intravenous cyclophosphamide for the corticosteroid-resistant nephrotic syndrome to which he responded remarkably well. His edema settled, proteinuria resolved, and liver functions normalized. Currently, he is in remission and enjoying good health. To the best of our knowledge, we report the first known association between IgM nephropathy and Wilson's disease. It is presently not clear if causation can necessarily be established. This may be the result of defective IgM clearance by the liver or an altered metabolism of the antibody or immune complexes, as with hepatic-associated immunoglobulin M (IgM) nephropathy. Further studies are needed to elucidate the exact mechanism of this disease.

  17. Intravenous immunoglobulins in children with new onset dilated cardiomyopathy.

    PubMed

    Heidendael, Josephine F; Den Boer, Suzanne L; Wildenbeest, Joanne G; Dalinghaus, Michiel; Straver, Bart; Pajkrt, Dasja

    2017-08-11

    Dilated cardiomyopathy is a rare but serious disorder in children. No effective diagnostic or treatment tools are readily available. This study aimed to evaluate the efficacy of intravenous immunoglobulins in children with new onset dilated cardiomyopathy. Methods and results In this retrospective cohort study, 94 children with new onset dilated cardiomyopathy were followed during a median period of 33 months. All patients with secondary dilated cardiomyopathy - for example, genetic, auto-immune or structural defects - had been excluded. Viral tests were performed in all patients and 18 (19%) children met the criteria for the diagnosis "probable or definite viral myocarditis". Intravenous immunoglobulins were administered to 21 (22%) patients. Overall transplant-free survival was 75% in 5 years and did not differ between treatment groups. The treatment was associated with a higher recovery rate within 5 years, compared with non-treated children (70 versus 43%, log rank=0.045). After correction for possible confounders the hazard ratio for recovery with intravenous immunoglobulins was not significant (hazard ratio: 2.1; 95% CI: 1.0-4.6; p=0.056). Administration of intravenous immunoglobulins resulted in a greater improvement in the shortening fraction of the left ventricle. In our population of children with new onset dilated cardiomyopathy, of either viral or idiopathic origin, intravenous immunoglobulins were administered to a minority of the patients and did not influence transplant-free survival, but were associated with better improvement of systolic left ventricular function and with better recovery. Our results support the concept that children with new onset dilated cardiomyopathy might benefit from intravenous immunoglobulins.

  18. Fractal aggregates in Titan's atmosphere

    NASA Astrophysics Data System (ADS)

    Cabane, M.; Rannou, P.; Chassefiere, E.; Israel, G.

    1993-04-01

    The cluster structure of Titan's atmosphere was modeled by using an Eulerian microphysical model with the specific formulation of microphysical laws applying to fractal particles. The growth of aggregates in the settling phase was treated by introducing the fractal dimension as a parameter of the model. The model was used to obtain a vertical distribution of size and number density of the aggregates for different production altitudes. Results confirm previous estimates of the formation altitude of photochemical aerosols. The vertical profile of the effective radius of aggregates was calculated as a function of the visible optical depth.

  19. Aggregated Computational Toxicology Online Resource

    EPA Pesticide Factsheets

    Aggregated Computational Toxicology Online Resource (AcTOR) is EPA's online aggregator of all the public sources of chemical toxicity data. ACToR aggregates data from over 1,000 public sources on over 500,000 chemicals and is searchable by chemical name, other identifiers and by chemical structure. It can be used to query a specific chemical and find all publicly available hazard, exposure and risk assessment data. It also provides access to EPA's ToxCast, ToxRefDB, DSSTox, Dashboard and DSSTox data.

  20. The patient: Emerging clinical applications of intravenous immunoglobulin.

    PubMed

    Harvey, R Donald

    2005-11-01

    Intravenous immunoglobulin (IGIV) originally was used as prophylactic treatment of infections in patients with primary immunodeficiency disease. Today, administration of IGIV, due in large part to its immunomodulatory activity, has expanded to include a number of other disorders. Available data suggest that the accepted indications for IGIV will continue to expand. As the number of clinical applications for this therapy grows, so will market opportunities; current preparations will be modified and improved and new products introduced. Intravenous immunoglobulin therapy has improved the lives of many patients with immune-related disorders. Future applications will ideally advance this paradigm further.

  1. Russell body duodenitis with immunoglobulin kappa light chain restriction.

    PubMed

    Munday, William R; Kapur, Lucy Harn; Xu, Mina; Zhang, Xuchen

    2015-01-16

    Russell bodies are eosinophilic intracytoplasmic globules which are likely the result of disturbed secretion of immunoglobulins that accumulate within the plasma cell. Russell body collections have been identified within the stomach, known as Russell body gastritis. Similar lesions within the duodenum are referred to as Russell body duodenitis, which is rare. Several Russell body gastritis case reports are associated with Helicobacter pylori. However, the etiology of Russell body duodenitis remains unclear. Here we report the first case of Russell body duodenitis with immunoglobulin light chain restriction in a background of peptic duodenitis.

  2. Intracranial reticulum cell sarcoma associated with immunoglobulin A deficiency

    PubMed Central

    Gregory, M. C.; Hughes, J. T.

    1973-01-01

    A case is reported of a 46 year old woman who died after a five month illness characterized by focal neurological signs, evidence of meningeal irritation, and the finding of `blast' cells in the CSF. Immunoglobulin A was consistently absent from her serum and secretions. Necropsy showed extensive infiltration by a reticulum-cell sarcoma of the subarachnoid space, with tumour nodules on several cranial nerves and tumour infiltration of the tuber cinereum. The significance of the association between immunoglobulin A deficiency and neoplasia is discussed. Images PMID:4356731

  3. Recombination events that activate, diversify, and delete immunoglobulin genes.

    PubMed

    Leder, P; Max, E E; Seidman, J G; Kwan, S P; Scharff, M; Nau, M; Norman, B

    1981-01-01

    Immunoglobulin kappa light-chain diversity arises, in large part, from an array of germ-line V-region genes that undergo somatic recombination with one of four active J-region segments. The diversity provided by this combinational system is increased by a recombination mechanism that allows variation of crossover points so as to generate additional diversity at a critical region of the light chain. The elaborate mechanism for generating diversity is accompanied not only by considerable waste, in terms of unused V and J regions in a given cell, but also by a range of aberrant recombinants that fail to produce active immunoglobulin genes.

  4. Methods for chromatofocusing of cerebrospinal fluid and serum immunoglobulin G.

    PubMed

    Gallo, P; Olsson, O; Sidén, A

    1985-06-26

    Chromatofocusing programs were designed for separations of submilligram amounts of normal and abnormal human IgG. The Pharmacia FPLC system, equipped with a Mono P column or a specially designed, small column was used for the separations. Normal IgG in paired cerebrospinal fluid and serum samples, paired samples from patients with intrathecal immunoglobulin G synthesis, as well as sera with IgG M components were examined. Abnormal immunoglobulin G components, especially those with pI values greater than ca. 7.0 pH units, were easily identified.

  5. Is injecting a finger with rabies immunoglobulin dangerous?

    PubMed

    Suwansrinon, Kanitta; Jaijaroensup, Wipaporn; Wilde, Henry; Sitprija, Visith

    2006-08-01

    Treating potentially rabies virus infected wounds requires the injection of rabies immunoglobulin into and around the wounds, followed by vaccination with an approved tissue culture rabies vaccine. A significant number of such bite wounds involves fingers where there is little space for expansion. Injecting immunoglobulin into such areas under pressure may induce a compartment syndrome caused by compromising circulation. We carried out a retrospective review and a prospective study of patients seen with digital bite injuries and found that it is a safe procedure if carried out with care by experienced staff.

  6. Distribution of maternal immunoglobulins in the mouse uterus and embryo in the days after implantation

    PubMed Central

    1977-01-01

    The distribution of maternal immunoglobulins in the mouse uterus and embryo in the days after implantation has been studied on sections incubated with sheep Fab anti-mouse immunoglobulins labeled with peroxidase. At the time of implantation the blastocyst is already surrounded by immunoglobulins that are also present in the blastocoel and early endoderm; uterine glands contain large amounts of immunoglobulins. Later, immunoglobulins are concentrated in the vacuolated endoderm, then the visceral yolk sac and the embryonic gut. They are also present in the various cavities of the embryo. Trophoblast cells progressively contain increasing amounts of immunoglobulins. In the decidua, immunoglobulins coat the cells and also occasionally appear as cytoplasmic granules. The early presence of maternal immunoglobulins may represent the transfer of serum proteins as a means of nutrition for the embryo. It is also very likely to have an immunological significance in the protection of the embryo. PMID:830790

  7. 21 CFR 866.5540 - Immunoglobulin G (Fd fragment specific) immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... fragment) of the heavy chain (a subunit) of the immunoglobulin antibody molecule in serum. Measurement of immunoglobulin G Fd fragments aids in the diagnosis of plasma antibody-forming cell abnormalities. (b...

  8. Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy.

    PubMed

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

    2013-12-30

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) causes progressive or relapsing weakness and numbness of the limbs, developing over at least two months. Uncontrolled studies suggest that intravenous immunoglobulin (IVIg) helps. This review was first published in 2002 and has since been updated, most recently in 2013. To review systematically the evidence from randomised controlled trials (RCTs) concerning the efficacy and safety of IVIg in CIDP. On 4 December 2012, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL (2012, issue 11 in the Cochrane Library), MEDLINE and EMBASE to December 2012 and ISI from January 1985 to May 2008. We searched for ongoing trials through two metaRegistries (World Health Organization International Clinical Trials Registry Platform Search Portal and Current Controlled Trials). We selected RCTs testing any dose of IVIg versus placebo, plasma exchange or corticosteroids in definite or probable CIDP. Two authors reviewed literature searches to identify potentially relevant RCTs, scored their quality and extracted data independently. We contacted authors for additional information. We considered eight RCTs, including 332 participants, to be eligible for inclusion in the review. These trials were homogeneous and the overall risk of bias low. Five studies, in a total of 235 participants compared IVIg against placebo. One trial with 20 participants compared IVIg with plasma exchange, one trial compared IVIg with prednisolone in 32 participants, and one trial, newly included at this update, compared IVIg with intravenous methylprednisolone in 46 participants.A significantly higher proportion of participants improved in disability within one month after IVIg treatment as compared with placebo (risk ratio (RR) 2.40, 95% confidence interval (CI) 1.72 to 3.36; number needed to treat for an additional beneficial outcome 3.03 (95% CI 2.33 to 4.55), high quality evidence). Whether all these improvements

  9. Surface fractals in liposome aggregation.

    PubMed

    Roldán-Vargas, Sándalo; Barnadas-Rodríguez, Ramon; Quesada-Pérez, Manuel; Estelrich, Joan; Callejas-Fernández, José

    2009-01-01

    In this work, the aggregation of charged liposomes induced by magnesium is investigated. Static and dynamic light scattering, Fourier-transform infrared spectroscopy, and cryotransmission electron microscopy are used as experimental techniques. In particular, multiple intracluster scattering is reduced to a negligible amount using a cross-correlation light scattering scheme. The analysis of the cluster structure, probed by means of static light scattering, reveals an evolution from surface fractals to mass fractals with increasing magnesium concentration. Cryotransmission electron microscopy micrographs of the aggregates are consistent with this interpretation. In addition, a comparative analysis of these results with those previously reported in the presence of calcium suggests that the different hydration energy between lipid vesicles when these divalent cations are present plays a fundamental role in the cluster morphology. This suggestion is also supported by infrared spectroscopy data. The kinetics of the aggregation processes is also analyzed through the time evolution of the mean diffusion coefficient of the aggregates.

  10. Cell aggregation: Packing soft grains

    NASA Astrophysics Data System (ADS)

    Åström, J. A.; Karttunen, M.

    2006-06-01

    Cellular aggregates may be considered as collections of membrane enclosed units with a pressure difference between the internal and external liquid phases. Cells are kept together by membrane adhesion and/or confined space compression. Pattern formation and, in particular, intercellular spacing have important roles in controlling solvent diffusion within such aggregates. A physical approach is used to study generic aspects of cellular packings in a confined space. Average material properties are derived from the free energy. The appearance of penetrating intercellular void channels is found to be critically governed by the cell wall adhesion mechanisms during the formation of dense aggregates. A fully relaxed aggregate efficiently hinders solvent diffusion at high hydrostatic pressures, while a small fraction (˜0.1) of adhesion related packing frustration is sufficient for breaking such a blockage even at high a pressure.

  11. Aggregate breakdown of nanoparticulate titania

    NASA Astrophysics Data System (ADS)

    Venugopal, Navin

    Six nanosized titanium dioxide powders synthesized from a sulfate process were investigated. The targeted end-use of this powder was for a de-NOx catalyst honeycomb monolith. Alteration of synthesis parameters had resulted principally in differences in soluble ion level and specific surface area of the powders. The goal of this investigation was to understand the role of synthesis parameters in the aggregation behavior of these powders. Investigation via scanning electron microscopy of the powders revealed three different aggregation iterations at specific length scales. Secondary and higher order aggregate strength was investigated via oscillatory stress rheometry as a means of simulating shear conditions encountered during extrusion. G' and G'' were measured as a function of the applied oscillatory stress. Oscillatory rheometry indicated a strong variation as a function of the sulfate level of the particles in the viscoelastic yield strengths. Powder yield stresses ranged from 3.0 Pa to 24.0 Pa of oscillatory stress. Compaction curves to 750 MPa found strong similarities in extrapolated yield point of stage I and II compaction for each of the powders (at approximately 500 MPa) suggesting that the variation in sulfate was greatest above the primary aggregate level. Scanning electron microscopy of samples at different states of shear in oscillatory rheometry confirmed the variation in the linear elastic region and the viscous flow regime. A technique of this investigation was to approach aggregation via a novel perspective: aggregates are distinguished as being loose open structures that are highly disordered and stochastic in nature. The methodology used was to investigate the shear stresses required to rupture the various aggregation stages encountered and investigate the attempt to realign the now free-flowing constituents comprising the aggregate into a denser configuration. Mercury porosimetry was utilized to measure the pore size of the compact resulting from

  12. An update on the use of immunoglobulin for the treatment of immunodeficiency disorders

    PubMed Central

    Albin, Stephanie; Cunningham-Rundles, Charlotte

    2015-01-01

    For patients with significant antibody deficiencies, immunoglobulin therapy is the mainstay of treatment as it significantly reduces both the frequency and severity of infections. The formulations and delivery methods of immunoglobulin have evolved over time, and continued improvements have allowed for increased access to this effective medication. This review is an update on the current status of immunoglobulin therapy in immunodeficiency disorders, and discusses the mechanisms, forms and dosing, and indications for immunoglobulin replacement. PMID:25428649

  13. Human eosinophils express the high affinity IgE receptor, FcεRI, in bullous pemphigoid.

    PubMed

    Messingham, Kelly N; Holahan, Heather M; Frydman, Alexandra S; Fullenkamp, Colleen; Srikantha, Rupasree; Fairley, Janet A

    2014-01-01

    Bullous pemphigoid (BP) is an autoimmune blistering disease mediated by autoantibodies targeting BP180 (type XVII collagen). Patient sera and tissues typically have IgG and IgE autoantibodies and elevated eosinophil numbers. Although the pathogenicity of the IgE autoantibodies is established in BP, their contribution to the disease process is not well understood. Our aims were two-fold: 1) To establish the clinical relationships between total and BP180-specific IgE, eosinophilia and other markers of disease activity; and 2) To determine if eosinophils from BP patients express the high affinity IgE receptor, FcεRI, as a potential mechanism of action for IgE in BP. Our analysis of 48 untreated BP patients revealed a correlation between BP180 IgG and both BP180 IgE and peripheral eosinophil count. Additionally, we established a correlation between total IgE concentration and both BP180 IgE levels and eosinophil count. When only sera from patients (n = 16) with total IgE ≥ 400 IU/ml were analyzed, BP180 IgG levels correlated with disease severity, BP230 IgG, total circulating IgE and BP180 IgE. Finally, peripheral eosinophil count correlated more strongly with levels of BP180 IgE then with BP180 IgG. Next, eosinophil FcεRI expression was investigated in the blood and skin using several methods. Peripheral eosinophils from BP patients expressed mRNA for all three chains (α, β and γ) of the FcεRI. Surface expression of the FcεRIα was confirmed on both peripheral and tissue eosinophils from most BP patients by immunostaining. Furthermore, using a proximity ligation assay, interaction of the α- and β-chains of the FcεRI was observed in some biopsy specimens, suggesting tissue expression of the trimeric receptor form in some patients. These studies provide clinical support for the relevance of IgE in BP disease and provide one mechanism of action of these antibodies, via binding to the FcεRI on eosinophils.

  14. Glycation precedes lens crystallin aggregation

    SciTech Connect

    Swamy, M.S.; Perry, R.E.; Abraham, E.C.

    1987-05-01

    Non-enzymatic glycosylation (glycation) seems to have the potential to alter the structure of crystallins and make them susceptible to thiol oxidation leading to disulfide-linked high molecular weight (HMW) aggregate formation. They used streptozotocin diabetic rats during precataract and cataract stages and long-term cell-free glycation of bovine lens crystallins to study the relationship between glycation and lens crystallin aggregation. HMW aggregates and other protein components of the water-soluble (WS) and urea-soluble (US) fractions were separated by molecular sieve high performance liquid chromatography. Glycation was estimated by both (/sup 3/H)NaBH/sub 4/ reduction and phenylboronate agarose affinity chromatography. Levels of total glycated protein (GP) in the US fractions were about 2-fold higher than in the WS fractions and there was a linear increase in GP in both WS and US fractions. This increase was parallelled by a corresponding increase in HMW aggregates. Total GP extracted by the affinity method from the US fraction showed a predominance of HMW aggregates and vice versa. Cell-free glycation studies with bovine crystallins confirmed the results of the animals studies. Increasing glycation caused a corresponding increase in protein insolubilization and the insoluble fraction thus formed also contained more glycated protein. It appears that lens protein glycation, HMW aggregate formation, and protein insolubilization are interrelated.

  15. Model for amorphous aggregation processes

    NASA Astrophysics Data System (ADS)

    Stranks, Samuel D.; Ecroyd, Heath; van Sluyter, Steven; Waters, Elizabeth J.; Carver, John A.; von Smekal, Lorenz

    2009-11-01

    The amorphous aggregation of proteins is associated with many phenomena, ranging from the formation of protein wine haze to the development of cataract in the eye lens and the precipitation of recombinant proteins during their expression and purification. While much literature exists describing models for linear protein aggregation, such as amyloid fibril formation, there are few reports of models which address amorphous aggregation. Here, we propose a model to describe the amorphous aggregation of proteins which is also more widely applicable to other situations where a similar process occurs, such as in the formation of colloids and nanoclusters. As first applications of the model, we have tested it against experimental turbidimetry data of three proteins relevant to the wine industry and biochemistry, namely, thaumatin, a thaumatinlike protein, and α -lactalbumin. The model is very robust and describes amorphous experimental data to a high degree of accuracy. Details about the aggregation process, such as shape parameters of the aggregates and rate constants, can also be extracted.

  16. Ash Aggregates in Proximal Settings

    NASA Astrophysics Data System (ADS)

    Porritt, L. A.; Russell, K.

    2012-12-01

    Ash aggregates are thought to have formed within and been deposited by the eruption column and plume and dilute density currents and their associated ash clouds. Moist, turbulent ash clouds are considered critical to ash aggregate formation by facilitating both collision and adhesion of particles. Consequently, they are most commonly found in distal deposits. Proximal deposits containing ash aggregates are less commonly observed but do occur. Here we describe two occurrences of vent proximal ash aggregate-rich deposits; the first within a kimberlite pipe where coated ash pellets and accretionary lapilli are found within the intra-vent sequence; and the second in a glaciovolcanic setting where cored pellets (armoured lapilli) occur within <1 km of the vent. The deposits within the A418 pipe, Diavik Diamond Mine, Canada, are the residual deposits within the conduit and vent of the volcano and are characterised by an abundance of ash aggregates. Coated ash pellets are dominant but are followed in abundance by ash pellets, accretionary lapilli and rare cored pellets. The coated ash pellets typically range from 1 - 5 mm in diameter and have core to rim ratios of approximately 10:1. The formation and preservation of these aggregates elucidates the style and nature of the explosive phase of kimberlite eruption at A418 (and other pipes?). First, these pyroclasts dictate the intensity of the kimberlite eruption; it must be energetic enough to cause intense fragmentation of the kimberlite to produce a substantial volume of very fine ash (<62 μm). Secondly, the ash aggregates indicate the involvement of moisture coupled with the presence of dilute expanded eruption clouds. The structure and distribution of these deposits throughout the kimberlite conduit demand that aggregation and deposition operate entirely within the confines of the vent; this indicates that aggregation is a rapid process. Ash aggregates within glaciovolcanic sequences are also rarely documented. The

  17. 21 CFR 866.5510 - Immunoglobulins A, G, M, D, and E immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulins A, G, M, D, and E immunological... Test Systems § 866.5510 Immunoglobulins A, G, M, D, and E immunological test system. (a) Identification. An immunoglobulins A, G, M, D, and E immunological test system is a device that consists of...

  18. Human myocytes are protected from titin aggregation-induced stiffening by small heat shock proteins

    PubMed Central

    Kötter, Sebastian; Unger, Andreas; Hamdani, Nazha; Lang, Patrick; Vorgerd, Matthias; Nagel-Steger, Luitgard

    2014-01-01

    In myocytes, small heat shock proteins (sHSPs) are preferentially translocated under stress to the sarcomeres. The functional implications of this translocation are poorly understood. We show here that HSP27 and αB-crystallin associated with immunoglobulin-like (Ig) domain-containing regions, but not the disordered PEVK domain (titin region rich in proline, glutamate, valine, and lysine), of the titin springs. In sarcomeres, sHSP binding to titin was actin filament independent and promoted by factors that increased titin Ig unfolding, including sarcomere stretch and the expression of stiff titin isoforms. Titin spring elements behaved predominantly as monomers in vitro. However, unfolded Ig segments aggregated, preferentially under acidic conditions, and αB-crystallin prevented this aggregation. Disordered regions did not aggregate. Promoting titin Ig unfolding in cardiomyocytes caused elevated stiffness under acidic stress, but HSP27 or αB-crystallin suppressed this stiffening. In diseased human muscle and heart, both sHSPs associated with the titin springs, in contrast to the cytosolic/Z-disk localization seen in healthy muscle/heart. We conclude that aggregation of unfolded titin Ig domains stiffens myocytes and that sHSPs translocate to these domains to prevent this aggregation. PMID:24421331

  19. Molecular analysis of the immunoglobulin genes in goose.

    PubMed

    Huang, Tian; Wu, Kun; Yuan, Xiaoli; Shao, Shuai; Wang, WenYuan; Wei, Si; Cao, Gengsheng

    2016-07-01

    Immunoglobulins play an important role in adaptive immune system as defense molecules against pathogens. However, our knowledge on avian immunoglobulin genes has been limited to a few species. In this study, we analyzed goose (Anser cygnoides orientalis) immunoglobulin genes. Three IgH classes including IgM, IgA, IgY and λ light chain were identified. The IgM and IgA heavy chain constant regions are characteristically similar to their counterparts described in other vertebrates. In addition to the classic Ig isotypes, we also detected a transcript that encoded a truncated form of IgY (IgY(ΔFc)) in goose. Similar to duck, the IgY(ΔFc) in goose was generated by using different transcriptional termination signal of the same υ gene. Limited variability and only one leader peptide were observed in VH and VL domains, which suggested that gene conversion was the primary mechanism involved in goose antibody diversity. Our study provides more insights into the immunoglobulin genes in goose that had not been fully explored before. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Structure and diversification of the bovine immunoglobulin repertoire.

    PubMed

    Aitken, R; Hosseini, A; MacDuff, R

    1999-12-15

    Our understanding of the basis to immunoglobulin formation in cattle has benefited substantially from the application of molecular biology over the past decade. It is now established that both the lambda light chain and heavy chain repertoires are founded upon the frequent expression of single gene families and subgroups of segments which are of conserved sequence. It is likely that a functional kappa locus exists in the bovine genome but this isotype comprises as few as 5% of bovine light chains. Similarly, alternative but non-expressed V(H) gene families are present posing intriguing but unresolved questions about the regulation of immunoglobulin synthesis. The heavy chain frequently bears a third complementarity-determining region which is atypically long but the processes which expand this region of the reading frame and its contribution to the interaction with antigen remain matters of speculation. Opportunities exist to map the major immunoglobulin loci and to define the membership and sequence diversity of the gene families which dominate each repertoire. However, it is already evident that cattle cannot generate significant diversity from rearrangement and junctional imprecision alone. Elucidation of the mechanism(s), dynamics and tissue distribution of immunoglobulin diversification in cattle, thus, remain key challenges in this branch of veterinary immunology.

  1. A case of immunoglobulin G4-related constrictive pericarditis

    PubMed Central

    Luo, Wen-Qi; Fang, Fang; Zhen, Wen-Jun; Ouyang, Xiao-Kang; Wang, Huai-Bin; Wang, Zi

    2016-01-01

    A 47-year-old man was admitted with a complaint of upper abdominal distension and shortness of breath. The constrictive pericarditis was diagnosed based on the transthoracic echocardiogram (TTE) and chest CT scan. Pathology revealed it is immunoglobulin (Ig) G4-related constrictive pericarditis. Likely, this is the first case of IgG4-related constrictive pericarditis reported in China. PMID:26904579

  2. A case of dermatomyositis with rhabdomyolysis, rescued by intravenous immunoglobulin.

    PubMed

    Mizoguchi, Fumitaka; Takada, Kazuki; Ishikawa, Kinya; Mizusawa, Hidehiro; Kohsaka, Hitoshi; Miyasaka, Nobuyuki

    2015-07-01

    We describe a case of severe dermatomyositis (DM) complicated by rhabdomyolysis, acute tubular necrosis, and hemophagocytosis. The case failed to respond to corticosteroids, but showed rapid and significant improvement after the addition of intravenous immunoglobulin (IVIG). While the prognosis of DM is poor when it is complicated by rhabdomyolysis, the early administration of IVIG has the potential to be the cornerstone of its management.

  3. Immunoglobulins against Tyrosine Nitrated Epitopes in Coronary Artery Disease

    PubMed Central

    Thomson, Leonor; Tenopoulou, Margarita; Lightfoot, Richard; Tsika, Epida; Parastatidis, Ioannis; Martinez, Marissa; Greco, Todd M.; Doulias, Paschalis-Thomas; Wu, Yuping; Tang, W. H. Wilson; Hazen, Stanley L.; Ischiropoulos, Harry

    2012-01-01

    Background Several lines of evidence support a pathophysiological role of immunity in atherosclerosis. Tyrosine nitrated proteins, a footprint of oxygen and nitrogen derived oxidants generated by cells of the immune system, are enriched in atheromatous lesions and in circulation of coronary artery disease (CAD) subjects. However, the consequences of possible immune reactions triggered by the presence of nitrated proteins in subjects with clinically documented atherosclerosis have not been explored. Methods and Results Specific immunoglobulins that recognize 3-nitrotyrosine epitopes were identified in human lesions, as well as in circulation of CAD subjects. The levels of circulating immunoglobulins against 3-nitrotyrosine epitopes were quantified in CAD patients (n=374) and subjects without CAD (non CAD controls, n=313). A ten-fold increase in the mean level of circulating immunoglobulins against protein-bound 3-nitrotyrosine was documented in the CAD subjects (3.75 ± 1.8 μg antibody Eq/mL plasma vs. 0.36 ± 0.8 μg antibody Eq/mL plasma), and was strongly associated with angiographic evidence of significant CAD. Conclusions The results of this cross sectional study suggest that post-translational modification of proteins via nitration within atherosclerotic plaque-laden arteries and in circulation serve as neoepitopes for elaboration of immunoglobulins, thereby providing an association between oxidant production and the activation of the immune system in CAD. PMID:23081989

  4. Stability of orally administered immunoglobulin in the gastrointestinal tract.

    PubMed

    Lee, Jeongmin; Kang, Hae-Eun; Woo, Hee-Jong

    2012-10-31

    Oral administration of immunoglobulin in the colostrum or egg yolk has been considered an effective tool for preventing enterobacterial infection via passive immunization. During this process, the transmission and residence of the active immunoglobulin are the most important conditions for successful protection. We investigated the stability of encapsulated colostrum and egg yolk immunoglobulin for the effective transmission of immunoglobulin in the gastrointestinal (GI) tract. First, we measured GI transit time. Contrast media passed through and reached the stomach within 10 min, the small intestine within 3.5 h, and the cecum within 5 h. Both the encapsulated colostrum containing anti-hepatitis A virus (HAV) antibody (IgG) and egg yolk with anti-rotavirus antibody (IgY) showed lower antibody activity than the non-encapsulated colostrum did in the stomach after administration; however, significantly higher antibody activities were observed in the encapsulated groups than in the non-encapsulated groups in the small intestine 3.5 h after the administration. In the large intestine, the antibody activities of the encapsulated groups were maintained or slightly increased in a time-dependent manner; however, the titers of each non-capsulated control were as low as the negative controls. Therefore, this encapsulation is considered a useful tool for the delivery of active antibody through the GI tract.

  5. Labile aggregation stimulating substance, free fatty acids, and platelet aggregation.

    PubMed

    Gerrard, J M; White, J G; Krivit, W

    1976-01-01

    Labile aggregation stimulating substance (LASS), an intermediate produced during platelet biosynthesis of PGE2 and PGF2alpha, acts as a physiologic intercellular messenger to promote platelet aggregation and the release reaction. The activity is formed by intact cells after physiologic stimulation or can be generated from platelet membrane fractions after combination with arachidonate. In the present investigation, small amounts of polyunsaturated fatty acids added to an incubation mixture of platelet microsomes and arachidonate were found to significantly inhibit subsequent platelet aggregation. Saturated and mono-unsaturated fatty acids in the same concentrations were without effect. However, in higher concentrations mono-unsaturated fatty acids were found to be inhibitory and stearic acid was found to enhance subsequent platelet aggregation. The inhibition caused by the polyunsaturated fatty acid, linoleate, was shown to be the result of an effect on the production of LASS through an interaction with the platelet enzyme responsible for conversion of arachidonate to LASS. In contrast, stearic acid was found to enhance platelet aggregation by acting on the platelets and not directly on LASS production. The results suggest that small changes in the fatty acid composition of platelet phospholipids could significantly influence platelet reactivity.

  6. [Clinical significance of analysis of immunoglobulin A levels in saliva].

    PubMed

    Bokor-Bratić, M

    2000-01-01

    SALIVA COLLECTION: Whole saliva is a product of secretion of 3 major glands (parotid, submandibular, sublingual) and many minor glands (labial, buccal, palatal). Unstimulated saliva is usually obtained as the patient spits out every 60 sec. or by forward bended head the patient allows saliva to drip off the lower lip into a cylinder. By collection of saliva in the tube the flow rate per unit time can be measured. When volume measurement is not required the saliva can be collected on cotton rolls, gauze or filter paper. For evaluating salivary gland function or when large volumes of saliva are required for analytic purposes, stimulated whole saliva is used. Method of collection is the same as for unstimulated saliva. The usual masticatory stimuli are paraffin wax or a washed rubber band. A standard gustatory stimulus is obtained by 2% citric acid applied directly to the tongue every 15 to 60 sec. Parotid saliva can be collected by aspiration from the duct opening with a micropipette. Parotid saliva is best collected with Lashley's vacuum chamber. Submandibular and sublingual saliva can be collected by cannulation of the duct with micropipette, but in practice this is both uncomfortable for the patients and technically difficult since the duct orifice is mobile and has a strong sphincter. Because of that, alginate and silicone impression material is used for retention of the collecting tube. As alternative and simple technique is to block off secretion from the parotid glands with absorbent swabs and collect mixed submandibular and sublingual saliva by pipette from the floor of the mouth. Saliva from labial and palatal glands can be collected by filter paper disc or disc of other synthetic materials. SALIVARY IMMUNOGLOBULIN A: The most significant characteristics of the salivary immunoglobulin system are quantitative domination of immunoglobulin A, local synthesis and specific structure. Immunofluorescence studies have shown that immunoglobulin A is produced by

  7. Immunoglobulin derived depositions in the nervous system: novel mass spectrometry application for protein characterization in formalin-fixed tissues.

    PubMed

    Rodriguez, Fausto J; Gamez, Jeffrey D; Vrana, Julie A; Theis, Jason D; Giannini, Caterina; Scheithauer, Bernd W; Parisi, Joseph E; Lucchinetti, Claudia F; Pendlebury, William W; Bergen, H Robert; Dogan, Ahmet

    2008-10-01

    Proteinaceous deposits are occasionally encountered in surgically obtained biopsies of the nervous system. Some of these are amyloidomas, although the precise nature of other cases remains uncertain. We studied 13 cases of proteinaceous aggregates in clinical specimens of the nervous system. Proteins contained within laser microdissected areas of interest were identified from tryptic peptide sequences by liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS). Immunohistochemical studies for immunoglobulin heavy and light chains and amyloidogenic proteins were performed in all cases. Histologically, the cases were classified into three groups: 'proteinaceous deposit not otherwise specified' (PDNOS) (n=6), amyloidoma (n=5), or 'intracellular crystals' (n=2). LC-MS/MS demonstrated the presence of lambda, but not kappa, light chain as well as serum amyloid P in all amyloidomas. lambda-Light-chain immunostaining was noted in amyloid (n=5), although demonstrable monotypic lymphoplasmacytic cells were seen in only one case. Conversely, in PDNOS kappa, but not lambda, was evident in five cases, both light chains being present in a single case. In three cases of PDNOS, a low-grade B-cell lymphoma consistent with marginal zone lymphoma was present in the brain specimen (n=2) or spleen (n=1). Lastly, in the 'intracellular crystals' group, the crystals were present within CD68+ macrophages in one case wherein kappa-light chain was found by LC-MS/MS only; the pathology was consistent with crystal-storing histiocytosis. In the second case, the crystals contained immunoglobulin G within CD138+ plasma cells. Our results show that proteinaceous deposits in the nervous system contain immunoglobulin components and LC-MS/MS accurately identifies the content of these deposits in clinical biopsy specimens. LC-MS/MS represents a novel application for characterization of these deposits and is of diagnostic utility in addition to standard immunohistochemical analyses.

  8. Mucosal immunoglobulins and B cells of Teleost fish

    PubMed Central

    Salinas, Irene; Zhang, Yong-An; Sunyer, J. Oriol

    2012-01-01

    As physical barriers that separate teleost fish from the external environment, mucosae are also active immunological sites that protect them against exposure to microbes and stressors. In mammals, the sites where antigens are sampled from mucosal surfaces and where stimulation of naive T and B lymphocytes occurs are known as inductive sites and are constituted by mucosa-associated lymphoid tissue (MALT). According to anatomical location, the MALT in teleost fish is subdivided into gut-associated lymphoid tissue (GALT), skin-associated lymphoid tissue (SALT), and gill-associated lymphoid tissue (GIALT). All MALT contain a variety of leukocytes, including, but not limited to, T cells, B cells, plasma cells, macrophages and granulocytes. Secretory immunoglobulins are produced mainly by plasmablasts and plasma cells, and play key roles in the maintenance of mucosal homeostasis. Until recently, teleost fish B cells were thought to express only two classes of immunoglobulins, IgM and IgD, in which IgM was thought to be the only one responding to pathogens both in systemic and mucosal compartments. However, a third teleost immunoglobulin class, IgT/IgZ, was discovered in 2005, and it has recently been shown to behave as the prevalent immunoglobulin in gut mucosal immune responses. The purpose of this review is to summarise the current knowledge of mucosal immunoglobulins and B cells of fish MALT. Moreover, we attempt to integrate the existing knowledge on both basic and applied research findings on fish mucosal immune responses, with the goal to provide new directions that may facilitate the development of novel vaccination strategies that stimulate not only systemic, but also mucosal immunity. PMID:22133710

  9. The immunoglobulin heavy chain locus in the platypus (Ornithorhynchus anatinus).

    PubMed

    Gambón-Deza, F; Sánchez-Espinel, C; Magadán-Mompó, S

    2009-08-01

    Immunoglobulins loci in mammals are well known to be organized within a translocon, however their origin remains unresolved. Four of the five classes of immunoglobulins described in humans and rodents (immunoglobulins M, G, E and A-IgM, IgG, IgE and IgA) were found in marsupials and monotremes (immunoglobulin D-IgD was not found) thus showing that the genomic structure of antibodies in mammals has remained constant since its origin. We have recently described the genomic organization of the immunoglobulin heavy chain locus in reptiles (IGHM, IGHD and IGHY). These data and the characterization of the IGH locus in platypus (Ornithorhynchus anatinus), allow us to elucidate the changes that took place in this genomic region during evolution from reptile to mammal. Thus, by using available genome data, we were able to detect that platypus IGH locus contains reptilian and mammalian genes. Besides having an IGHD that is very similar to the one in reptiles and an IGHY, they also present the mammal specific antibody genes IGHG and IGHE, in addition to IGHA. We also detected a pseudogene that originated by recombination between the IGHD and the IGHM (similar to the IGHD2 found in Eublepharis macularius). The analysis of the IGH locus in platypus shows that IGHY was duplicated, firstly by evolving into IGHE and then into IGHG. The IGHA of the platypus has a complex origin, and probably arose by a process of recombination between the IGHM and the IGHY. We detected about 44 VH genes (25 were already described), most of which comprise a single group. When we compared these VH genes with those described in Anolis carolinensis, we find that there is an evolutionary relationship between the VH genes of platypus and the reptilian Group III genes. These results suggest that a fast VH turnover took place in platypus and this gave rise to a family with a high VH gene number and the disappearance of the earlier VH families.

  10. Mucosal immunoglobulins and B cells of teleost fish.

    PubMed

    Salinas, Irene; Zhang, Yong-An; Sunyer, J Oriol

    2011-12-01

    As physical barriers that separate teleost fish from the external environment, mucosae are also active immunological sites that protect them against exposure to microbes and stressors. In mammals, the sites where antigens are sampled from mucosal surfaces and where stimulation of naïve T and B lymphocytes occurs are known as inductive sites and are constituted by mucosa-associated lymphoid tissue (MALT). According to anatomical location, the MALT in teleost fish is subdivided into gut-associated lymphoid tissue (GALT), skin-associated lymphoid tissue (SALT), and gill-associated lymphoid tissue (GIALT). All MALT contain a variety of leukocytes, including, but not limited to, T cells, B cells, plasma cells, macrophages and granulocytes. Secretory immunoglobulins are produced mainly by plasmablasts and plasma cells, and play key roles in the maintenance of mucosal homeostasis. Until recently, teleost fish B cells were thought to express only two classes of immunoglobulins, IgM and IgD, in which IgM was thought to be the only one responding to pathogens both in systemic and mucosal compartments. However, a third teleost immunoglobulin class, IgT/IgZ, was discovered in 2005, and it has recently been shown to behave as the prevalent immunoglobulin in gut mucosal immune responses. The purpose of this review is to summarise the current knowledge of mucosal immunoglobulins and B cells of fish MALT. Moreover, we attempt to integrate the existing knowledge on both basic and applied research findings on fish mucosal immune responses, with the goal to provide new directions that may facilitate the development of novel vaccination strategies that stimulate not only systemic, but also mucosal immunity.

  11. The T-cell receptor as immunoglobulin: paradigm regained.

    PubMed

    Marchalonis, J J; Schluter, S F; Edmundson, A B

    1997-12-01

    The quest to determine the molecular nature of T-lymphocyte receptors for antigen was a "holy grail" to immunologists for over 25 years. This paper updates a review written 15 years ago (Marchalonis JJ, Hunt JC. Proc Soc Exp Biol Med 171:127-145, 1982), which proposed that "these molecules apparently do not bear determinants specified by the major histocompatibility complex, but express Ig-related variable regions and constant regions unique to T-cell products." We review subsequent contributions from molecular biology, protein chemistry, peptide immunochemistry, and structural biology establishing that T-cell receptors (TCRs) are members of the immunoglobulin family restricted to T cells that share 3-dimensional structural features, sequence homology, antigenic cross-reactivity, and common mechanisms of diversification with conventional immunoglobulins. These molecules and their light- and heavy-chain siblings appeared contemporaneously in vertebrate evolution with the emergence of sharks. We illustrate how extrapolation of concepts from immunoglobulin to T-cell receptors has aided in the understanding of these often enigmatic molecules, and, conversely, how concepts derived for T-cell receptors such as the role of "superantigens" can be directly applied to conventional immunoglobulins. A second precept that follows from the symmetry of the combining sites of Igs and TCRs is that MHC-restricted antibodies should exist. Such molecules have in fact been reported, and the x-ray crystallography for T-cell receptors suggests that the combining sites recognizing simultaneously MHC and peptide epitopes resemble the combining sites of antibodies directed against protein determinants. Additional immunoglobulin molecules of nonmammalian species have been detected and characterized based upon conserved homology to TCR and Igs, and it is anticipated that further study will enable the identification of more antigen-specific members of the family in mammals as well.

  12. Effect of therapeutic plasma exchange on immunoglobulins in myasthenia gravis.

    PubMed

    Guptill, Jeffrey T; Juel, Vern C; Massey, Janice M; Anderson, Amanda C; Chopra, Manisha; Yi, John S; Esfandiari, Ehsanollah; Buchanan, Tim; Smith, Bryan; Atherfold, Paul; Jones, Emma; Howard, James F

    2016-11-01

    An integrated understanding of therapeutic plasma exchange (TPE) effects on immunoglobulins, autoantibodies, and natural or acquired (vaccine) protective antibodies in patients with autoimmune myasthenia gravis (MG) is lacking. Prior studies measured TPE effects in healthy volunteers or heterogeneous autoimmune disease populations. We prospectively profiled plasma IgA, IgM, IgG, IgG subclasses (IgG1-4), acetylcholine receptor autoantibodies (AChR+), and protective antibodies in patients with AChR + MG receiving TPE for an exacerbation. TPE was performed according to institutional practice and patients were profiled for up to 12 weeks. Ten patients were enrolled (median age = 72.9 years; baseline MG-Composite = 21; median TPE treatments = 6 during their first course) and all improved. The maximum decrease in all immunoglobulins, including AChR autoantibodies, was achieved on the final day of the first TPE course (∼60-70% reduction). Three weeks post-TPE, mean AChR autoantibody, total IgG, IgG1, and IgG2 titers were below the reference range and had not recovered within 20% of baseline, whereas other measured immunoglobulins approached baseline values. We did not generally observe an "overshoot" of immunoglobulins above pre-TPE levels or accelerated recovery of pathologic AChR autoantibodies. Protective antibody profiles showed similar patterns as other IgGs and were detectable at levels associated with protection from infection. A slow return to baseline for IgGs (except IgG3) was observed, and we did not observe any obvious effect of concomitant medications on this recovery. Collectively, these findings enhance our understanding of the immunological effects of TPE and further support the concept of rapid immunoglobulin depletion for the treatment of patients with MG.

  13. Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection

    PubMed Central

    Zheng, Xuexing; Wong, Gary; Zhao, Yongkun; Wang, Hualei; He, Shihua; Bi, Yuhai; Chen, Weijin; Jin, Hongli; Gai, Weiwei; Chu, Di; Cao, Zengguo; Wang, Chong; Fan, Quanshui; Chi, Hang; Gao, Yuwei; Wang, Tiecheng; Feng, Na; Yan, Feihu; Huang, Geng; Zheng, Ying; Li, Nan; Li, Yuetao; Qian, Jun; Zou, Yong; Kobinger, Gary; Gao, George Fu; Qiu, Xiangguo; Yang, Songtao; Xia, Xianzhu

    2016-01-01

    Recent successes with monoclonal antibody cocktails ZMappTM and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. Since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived. To decrease the possibility of serum sickness, the equine antisera was digested with pepsin to generate F(ab′)2 fragments, with in vitro neutralizing activity comparable to whole immunoglobulin. Full protection was achieved with when treatment was initiated at 1 dpi, but the suboptimal protection observed with the 30 minute and 2 dpi groups demonstrate that in addition to virus neutralization, other Fc-dependent antibody mechanisms may also contribute to survival. Guinea pigs given 20 mg of antisera or F(ab′)2 at or starting at 1 or 2 dpi were also fully protected from EBOV infection. These results justify future efficacy studies for purified equine products in NHPs. PMID:27067649

  14. Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection.

    PubMed

    Zheng, Xuexing; Wong, Gary; Zhao, Yongkun; Wang, Hualei; He, Shihua; Bi, Yuhai; Chen, Weijin; Jin, Hongli; Gai, Weiwei; Chu, Di; Cao, Zengguo; Wang, Chong; Fan, Quanshui; Chi, Hang; Gao, Yuwei; Wang, Tiecheng; Feng, Na; Yan, Feihu; Huang, Geng; Zheng, Ying; Li, Nan; Li, Yuetao; Qian, Jun; Zou, Yong; Kobinger, Gary; Gao, George Fu; Qiu, Xiangguo; Yang, Songtao; Xia, Xianzhu

    2016-04-12

    Recent successes with monoclonal antibody cocktails ZMapp(TM) and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. Since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived. To decrease the possibility of serum sickness, the equine antisera was digested with pepsin to generate F(ab')2 fragments, with in vitro neutralizing activity comparable to whole immunoglobulin. Full protection was achieved with when treatment was initiated at 1 dpi, but the suboptimal protection observed with the 30 minute and 2 dpi groups demonstrate that in addition to virus neutralization, other Fc-dependent antibody mechanisms may also contribute to survival. Guinea pigs given 20 mg of antisera or F(ab')2 at or starting at 1 or 2 dpi were also fully protected from EBOV infection. These results justify future efficacy studies for purified equine products in NHPs.

  15. Linear immunoglobulin A/immunoglobulin G bullous dermatosis associated with Vogt-Koyanagi-Harada disease.

    PubMed

    Yanagihara, Shigeto; Mizuno, Nobuyuki; Naruse, Akiko; Tateishi, Chiharu; Tsuruta, Daisuke; Ishii, Masamitsu

    2011-08-01

    Vogt-Koyanagi-Harada disease is characterized by marked bilateral uveitis associated with symmetric vitiligo, alopecia, poliosis and dysacousia. Linear immunoglobulin (Ig)A bullous dermatosis (LABD) is characterized by small, tense, subepidermal bullae caused by IgA type autoantibody targeting the basal lamina. LABD patients sometimes show coexistence of IgG type autoantibody, termed linear IgA/IgG bullous dermatosis (LAGBD). We reported a 35-year-old Japanese male case of combined LAGBD and Vogt-Koyanagi-Harada disease. His human leukocyte antigen typing was -A24, B52, C*1202, DR*1502, DQ*0601. Immunoblot revealed that patient sera reacted to both 180- and 230-kDa proteins at the IgA and IgG level. Because Vogt-Koyanagi-Harada disease and LABD are reported to be associated with other autoimmune diseases, it is probable that Vogt-Koyanagi-Harada disease and LAGBD in our case may be associated with each other in the pathomechanism. However, we cannot exclude the possibility of this being mere coincidence.

  16. Fractal Aggregates in Tennis Ball Systems

    ERIC Educational Resources Information Center

    Sabin, J.; Bandin, M.; Prieto, G.; Sarmiento, F.

    2009-01-01

    We present a new practical exercise to explain the mechanisms of aggregation of some colloids which are otherwise not easy to understand. We have used tennis balls to simulate, in a visual way, the aggregation of colloids under reaction-limited colloid aggregation (RLCA) and diffusion-limited colloid aggregation (DLCA) regimes. We have used the…

  17. Fractal Aggregates in Tennis Ball Systems

    ERIC Educational Resources Information Center

    Sabin, J.; Bandin, M.; Prieto, G.; Sarmiento, F.

    2009-01-01

    We present a new practical exercise to explain the mechanisms of aggregation of some colloids which are otherwise not easy to understand. We have used tennis balls to simulate, in a visual way, the aggregation of colloids under reaction-limited colloid aggregation (RLCA) and diffusion-limited colloid aggregation (DLCA) regimes. We have used the…

  18. Tandem repeating modular proteins avoid aggregation in single molecule force spectroscopy experiments.

    PubMed

    Dougan, Lorna; Fernandez, Julio M

    2007-12-13

    We have used single molecule force spectroscopy to explore the unfolding and refolding behavior of the immunoglobulin-like I27 protein in aqueous 2,2,2-trifluoroethanol (TFE). In bulk solution experiments, a 28% v/v TFE solution has previously been observed to enhance intermolecular attractions and lead to misfolding and aggregation of tandem modular proteins of high sequence identity. In our single molecule experiments, however, we measure successful refolding of the polyprotein I27(8) in all TFE solutions up to 35% v/v. Using a single molecule micromanipulation technique, we have shown that refolding of a polyprotein with identical repeats is not hindered by the presence of this cosolvent. These experimental results provide new insight into the properties of tandem repeating proteins and raise interesting questions as to the evolutionary success of such proteins in avoiding misfolding and aggregation.

  19. The protective effect of modified intravenous immunoglobulin in LPS sepsis model is associated with an increased IRA B cells response.

    PubMed

    Djoumerska-Alexieva, Iglika; Pashova, Shina; Vassilev, Tchavdar; Pashov, Anastas

    2013-04-01

    Intravenous immunoglobulin preparations (IVIg) that have undergone a mild oxidizing treatment with ferrous ions have an increased polyspecificity, which is not associated with a higher propensity to form aggregates. Among other biological properties of the modified IVIg, a protective effect in LPS sepsis model stands out as the native preparation is totally devoid of it or even exacerbates sepsis. A recent finding identified an LPS induced subset of B1 lymphocytes that migrate from the peritoneal cavity to the spleen acquiring the expression of CD93, GM-CSF as well as the capacity to control sepsis. This report demonstrates that modified IVIg, but not the native preparation, causes a further increase in this population during LPS sepsis. Partial targeted suppression of the peritoneal B cell proliferation by an intracellular dye abrogates this effect and the clinical benefit of modified IVIg.

  20. Polyclonal immunoglobulins and hyperimmune globulins in prevention and management of infectious diseases.

    PubMed

    Hsu, Jennifer L; Safdar, Nasia

    2011-12-01

    Immunoglobulin therapy has a rich history of use in preventing and treating infectious diseases; however, clinical data on the efficacy of immunoglobulin is lacking for many infectious diseases. Immunoglobulin therapy is routinely used in postexposure prophylaxis for bacterial infections, including tetanus, botulism, and diphtheria, and viral infections, including hepatitis A and B and varicella. Immunoglobulin therapy has also been used in many severe and life-threatening infections where treatments are limited, including toxic shock syndrome, respiratory syncytial virus infection, and cytomegalovirus infection. The authors review the evidence for the use of immunoglobulin therapy in common adult infectious diseases. Copyright © 2011. Published by Elsevier Inc.

  1. Spatial aggregation: Language and applications

    SciTech Connect

    Bailey-Kellogg, C.; Zhao, F.; Yip, K.

    1996-12-31

    Spatial aggregation is a framework for organizing computations around image-like, analogue representations of physical processes in data interpretation and control tasks. It conceptualizes common computational structures in a class of implemented problem solvers for difficult scientific and engineering problems. It comprises a mechanism, a language, and a programming style. The spatial aggregation mechanism transforms a numerical input field to successively higher-level descriptions by applying a small, identical set of operators to each layer given a metric, neighborhood relation and equivalence relation. This paper describes the spatial aggregation language and its applications. The spatial aggregation language provides two abstract data types - neighborhood graph and field - and a set of interface operators for constructing the transformations of the field, together with a library of component implementations from which a user can mix-and-match and specialize for a particular application. The language allows users to isolate and express important computational ideas in different problem domains while hiding low-level details. We illustrate the use of the language with examples ranging from trajectory grouping in dynamics interpretation to region growing in image analysis. Programs for these different task domains can be written in a modular, concise fashion in the spatial aggregation language.

  2. Thermodynamic modeling of asphaltene aggregation.

    PubMed

    Rogel, E

    2004-02-03

    A new molecular thermodynamic model for the description of the aggregation behavior of asphaltenes in different solvents is presented. This new model is relatively simple and strictly predictive and does not use any experimental information from asphaltene solutions. In this model, asphaltene aggregates are described as composed of an aromatic core formed by stacked aromatic sheets surrounded by aliphatic chains. The proposed model qualitatively predicts the asphaltene aggregation behavior in a series of different solvents. In particular, the experimental trends observed for the variation of aggregate size with (1) asphaltene molecular characteristics (condensation index, aromaticity, and chain length), (2) asphaltene concentration, (3) solvent characteristics, and (4) temperature have been successfully reproduced by the proposed model. The model also provides a plausible explanation for the existence or absence of a critical micelle concentration (cmc) for asphaltene solutions. Specifically, the model predicted that the asphaltenes with low aromaticities and low aromatic condensations do not exhibit cmc behavior. Finally, the obtained results clearly support the classical model for asphaltene aggregates.

  3. Leaching behaviour of synthetic aggregates.

    PubMed

    van der Sloot, H A; Hoede, D; Cresswell, D J; Barton, J R

    2001-01-01

    In the framework of EU project "Utilising innovative kiln technology to recycle waste into synthetic aggregate" (BRST-CT98-5234), the leaching behaviour of synthetic aggregates has been studied to assess its environmental compatibility in the various stages of its use. Since the conditions are very different for the different uses, the assessment calls for a variety of different leaching conditions. The pH dependence test is used to cover important differences in pH environment to which the materials are exposed to as well as for an assessment of the buffering capacity of the material. Synthetic aggregate features a low buffer capacity, which makes it sensitive to externally imposed pH conditions. Utilisation and storage exposed to acidic conditions needs to be avoided. The results of the pH dependence test and column leaching test are mutually consistent. The CEN TC 154 method appears to provide systematically low values due to the arbitrary selection of test conditions. Synthetic aggregate studied to date will not adversely affect the concrete in its service life. The main issue for aggregate use is the recycling and the "end of life" condition, when the material becomes construction debris. Not metals, but oxyanions, such as Cr VI and Mo are most relevant under these conditions. A concise test has been applied to assess crucial aspects of leaching for different production mixes.

  4. Aggregated Recommendation through Random Forests

    PubMed Central

    2014-01-01

    Aggregated recommendation refers to the process of suggesting one kind of items to a group of users. Compared to user-oriented or item-oriented approaches, it is more general and, therefore, more appropriate for cold-start recommendation. In this paper, we propose a random forest approach to create aggregated recommender systems. The approach is used to predict the rating of a group of users to a kind of items. In the preprocessing stage, we merge user, item, and rating information to construct an aggregated decision table, where rating information serves as the decision attribute. We also model the data conversion process corresponding to the new user, new item, and both new problems. In the training stage, a forest is built for the aggregated training set, where each leaf is assigned a distribution of discrete rating. In the testing stage, we present four predicting approaches to compute evaluation values based on the distribution of each tree. Experiments results on the well-known MovieLens dataset show that the aggregated approach maintains an acceptable level of accuracy. PMID:25180204

  5. Channel Aggregation Schemes for Cognitive Radio Networks

    NASA Astrophysics Data System (ADS)

    Lee, Jongheon; So, Jaewoo

    This paper proposed three channel aggregation schemes for cognitive radio networks, a constant channel aggregation scheme, a probability distribution-based variable channel aggregation scheme, and a residual channel-based variable channel aggregation scheme. A cognitive radio network can have a wide bandwidth if unused channels in the primary networks are aggregated. Channel aggregation schemes involve either constant channel aggregation or variable channel aggregation. In this paper, a Markov chain is used to develop an analytical model of channel aggregation schemes; and the performance of the model is evaluated in terms of the average sojourn time, the average throughput, the forced termination probability, and the blocking probability. Simulation results show that channel aggregation schemes can reduce the average sojourn time of cognitive users by increasing the channel occupation rate of unused channels in a primary network.

  6. Influence of experimental alcohol administration on serum immunoglobulin levels: contrasting effects on IgE and other immunoglobulin classes.

    PubMed

    Alonso, M; Gomez-Rial, J; Gude, F; Vidal, C; Gonzalez-Quintela, A

    2012-01-01

    In humans, alcoholic liver disease is associated with hypergammaglobulinemia, particularly with high serum concentrations of IgA. Furthermore, alcohol consumption is associated with high concentrations of IgE and low concentrations of IgG. However, there is little experimental evidence to corroborate these observational findings. The objective of the present study was to investigate the potential short-term effects of alcohol administration on serum immunoglobulin concentrations in mice, and the potential influence of sex and strain on these effects. Eight mouse groups were defined by strain (Swiss vs C57BL/6), sex (male vs female), and experimental procedure (alcohol administration vs control diet). Alcohol was administered in a semi-liquid diet (6.5%v/v); control animals received an isocaloric semi-liquid diet. Immunoglobulin concentrations (IgE, IgA, IgM, IgG1, IgG2a, IgG2b, and IgG3) were measured at baseline and weekly thereafter for 4 weeks. Serum Th1 (interferon-gamma) and Th2 (IL-4 and IL-13) cytokines were measured at week 4. We found significant variations in baseline immunoglobulin concentrations depending upon mouse sex and strain. Alcohol administration was quickly followed by an increase in serum IgE concentrations in all experimental groups. IgE increase was correlated with serum IL-13 increase. In contrast, alcohol administration was not associated with significant changes in serum IgA and IgM concentration, and appeared to decrease IgG subclass concentrations. Alcohol effects on immunoglobulin concentrations were independent of mouse strain and sex. In conclusion, alcohol administration in mice had contrasting effects on IgE and other immunoglobulin classes. This experimental evidence confirms observational results in humans.

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

    PubMed

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

    2013-01-01

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

  8. The liquid protein phase in crystallization: a case study—intact immunoglobulins

    NASA Astrophysics Data System (ADS)

    Kuznetsov, Yurii G.; Malkin, Alexander J.; McPherson, Alexander

    2001-11-01

    A common observation by protein chemists has been the appearance, for many proteins in aqueous solutions, of oil like droplets, or in more extreme cases the formation of a second oil like phase. These may accompany the formation of precipitate in "salting out" or "salting in' procedures, but more commonly appear in place of any precipitate. Such phase separations also occur, with even greater frequency, in the presence of polymeric precipitants such as polyethyleneglycol (PEG). In general the appearance of a second liquid phase has been taken as indicative of protein aggregation, though an aggregate state distinctly different from that characteristic of amorphous precipitate. While the latter is thought to be composed of linear and branched assemblies, polymers of a sort, the oil phase suggests a more compact, three-dimensional, but fluid state. An important property of an alternate, fluid phase is that it can mediate transitions between other states, for example, between protein molecules free in solution and protein molecules immobilized in amorphous precipitate or crystals. The "liquid protein" phase can be readily observed in many crystallization experiments either prior to the appearance of visible crystals, or directly participating in the crystal growth process. In some cases the relationship between the liquid phase and developing crystals is intimate. Crystals grow directly from the liquid phase, or appear only after the visible formation of the liquid phase. We describe here our experience with a class of macromolecules, immunoglobulins, and particularly IDEC-151, an IgG specific for CD4 on human lymphocytes. This protein has been crystallized from a Jeffamine-LiSO 4 mother liquor and, its crystallization illustrates many of the features associated with the liquid protein, or protein rich phase.

  9. Fractal aggregates in tennis ball systems

    NASA Astrophysics Data System (ADS)

    Sabin, J.; Bandín, M.; Prieto, G.; Sarmiento, F.

    2009-09-01

    We present a new practical exercise to explain the mechanisms of aggregation of some colloids which are otherwise not easy to understand. We have used tennis balls to simulate, in a visual way, the aggregation of colloids under reaction-limited colloid aggregation (RLCA) and diffusion-limited colloid aggregation (DLCA) regimes. We have used the images of the cluster of balls, following Forrest and Witten's pioneering studies on the aggregation of smoke particles, to estimate their fractal dimension.

  10. Customer Aggregation: An Opportunity for Green Power?

    SciTech Connect

    Holt, E.; Bird, L.

    2001-02-26

    We undertook research into the experience of aggregation groups to determine whether customer aggregation offers an opportunity to bring green power choices to more customers. The objectives of this report, therefore, are to (1) identify the different types of aggregation that are occurring today, (2) learn whether aggregation offers an opportunity to advance sales of green power, and (3) share these concepts and approaches with potential aggregators and green power advocates.

  11. Molecular Aggregation in Disodium Cromoglycate

    NASA Astrophysics Data System (ADS)

    Singh, Gautam; Agra-Kooijman, D.; Collings, P. J.; Kumar, Satyendra

    2012-02-01

    Details of molecular aggregation in the mesophases of the anti-asthmatic drug disodium cromoglycate (DSCG) have been studied using x-ray synchrotron scattering. The results show two reflections, one at wide angles corresponding to π-π stacking (3.32 å) of molecules, and the other at small angles which is perpendicular to the direction of molecular stacking and corresponds to the distance between the molecular aggregates. The latter varies from 35 - 41 å in the nematic (N) phase and 27 -- 32 å in the columnar (M) phase. The temperature evolution of the stack height, positional order correlations in the lateral direction, and orientation order parameter were determined in the N, M, and biphasic regions. The structure of the N and M phases and the nature of the molecular aggregation, together with their dependence on temperature and concentration, will be presented.

  12. Equilibrium structure of ferrofluid aggregates.

    PubMed

    Yoon, Mina; Tománek, David

    2010-11-17

    We study the equilibrium structure of large but finite aggregates of magnetic dipoles, representing a colloidal suspension of magnetite particles in a ferrofluid. With increasing system size, the structural motif evolves from chains and rings to multi-chain and multi-ring assemblies. Very large systems form single- and multi-wall coils, tubes and scrolls. These structural changes result from a competition between various energy terms, which can be approximated analytically within a continuum model. We also study the effect of external parameters such as magnetic field on the relative stability of these structures. Our results may give insight into experimental data obtained during solidification of ferrofluid aggregates at temperatures where thermal fluctuations become negligible in comparison to inter-particle interactions. These data may also help to experimentally control the aggregation of magnetic particles.

  13. Equilibrium structure of ferrofluid aggregates

    SciTech Connect

    Yoon, Mina; Tomanek, David

    2010-01-01

    We study the equilibrium structure of large but finite aggregates of magnetic dipoles, representing a colloidal suspension of magnetite particles in a ferrofluid. With increasing system size, the structural motif evolves from chains and rings to multi-chain and multi-ring assemblies. Very large systems form single- and multi-wall coils, tubes and scrolls. These structural changes result from a competition between various energy terms, which can be approximated analytically within a continuum model. We also study the effect of external parameters such as magnetic field on the relative stability of these structures. Our results may give insight into experimental data obtained during solidification of ferrofluid aggregates at temperatures where thermal fluctuations become negligible in comparison to inter-particle interactions. These data may also help to experimentally control the aggregation of magnetic particles.

  14. Global kinetic analysis of seeded BSA aggregation.

    PubMed

    Sahin, Ziya; Demir, Yusuf Kemal; Kayser, Veysel

    2016-04-30

    Accelerated aggregation studies were conducted around the melting temperature (Tm) to elucidate the kinetics of seeded BSA aggregation. Aggregation was tracked by SEC-HPLC and intrinsic fluorescence spectroscopy. Time evolution of monomer, dimer and soluble aggregate concentrations were globally analysed to reliably deduce mechanistic details pertinent to the process. Results showed that BSA aggregated irreversibly through both sequential monomer addition and aggregate-aggregate interactions. Sequential monomer addition proceeded only via non-native monomers, starting to occur only by 1-2°C below the Tm. Aggregate-aggregate interactions were the dominant mechanism below the Tm due to an initial presence of small aggregates that acted as seeds. Aggregate-aggregate interactions were significant also above the Tm, particularly at later stages of aggregation when sequential monomer addition seemed to cease, leading in some cases to insoluble aggregate formation. The adherence (or non-thereof) of the mechanisms to Arrhenius kinetics were discussed alongside possible implications of seeding for biopharmaceutical shelf-life and spectroscopic data interpretation, the latter of which was found to often be overlooked in BSA aggregation studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. A specialist's audit of aggregated occurrence records: An 'aggregator's' perspective.

    PubMed

    Belbin, Lee; Daly, Joanne; Hirsch, Tim; Hobern, Donald; Salle, John La

    2013-01-01

    A recent ZooKeys' paper (Mesibov, 2013: http://www.pensoft.net/journal_home_page.php?journal_id=1&page=article&SESID=df7bcb35b02603283dcb83ee0e0af0c9&type=show&article_id=5111) has highlighted data quality issues in aggregated data sets, but did not provide a realistic way to address these issues. This paper provides an aggregator's perspective including ways that the whole community can help to address data quality issues. The establishment of GBIF and national nodes (national aggregators) such as the Atlas of Living Australia (ALA) have integrated and exposed a huge diversity of biological observations along with many associated issues. Much of the admirable work by Mesibov (2013) was enabled by having the data exposed. Data quality, one of the highest priorities for GBIF, the national nodes and other aggregators, depends on both automatic methods and community experts to detect and correct data issues. Not all issues can however be automatically detected or corrected, so community assistance is needed to help improve the quality of exposed biological data. We do need to improve the infrastructure and associated processes to more easily identify data issues and document all changes to ensure a full record is permanently and publicly available.

  16. Environmentalism and natural aggregate mining

    USGS Publications Warehouse

    Drew, L.J.; Langer, W.H.; Sachs, J.S.

    2002-01-01

    Sustaining a developed economy and expanding a developing one require the use of large volumes of natural aggregate. Almost all human activity (commercial, recreational, or leisure) is transacted in or on facilities constructed from natural aggregate. In our urban and suburban worlds, we are almost totally dependent on supplies of water collected behind dams and transported through aqueducts made from concrete. Natural aggregate is essential to the facilities that produce energy-hydroelectric dams and coal-fired powerplants. Ironically, the utility created for mankind by the use of natural aggregate is rarely compared favorably with the environmental impacts of mining it. Instead, the empty quarries and pits are seen as large negative environmental consequences. At the root of this disassociation is the philosophy of environmentalism, which flavors our perceptions of the excavation, processing, and distribution of natural aggregate. The two end-member ideas in this philosophy are ecocentrism and anthropocentrism. Ecocentrism takes the position that the natural world is a organism whose arteries are the rivers-their flow must not be altered. The soil is another vital organ and must not be covered with concrete and asphalt. The motto of the ecocentrist is "man must live more lightly on the land." The anthropocentrist wants clean water and air and an uncluttered landscape for human use. Mining is allowed and even encouraged, but dust and noise from quarry and pit operations must be minimized. The large volume of truck traffic is viewed as a real menace to human life and should be regulated and isolated. The environmental problems that the producers of natural aggregate (crushed stone and sand and gravel) face today are mostly difficult social and political concerns associated with the large holes dug in the ground and the large volume of heavy truck traffic associated with quarry and pit operations. These concerns have increased in recent years as society's demand for

  17. Molecular aggregates in cryogenic solutions

    NASA Astrophysics Data System (ADS)

    Schauer, M. W.; Lee, J.; Bernstein, E. R.

    1981-07-01

    In this report, experimental procedures and results concerning the study of aggregates are presented. Absorption spectra of solutions of the following solutes and solvents have been studied: pyrazine/C3H8; benzene/NF3, C3H8, N2, CO, CF4; and osmium tetroxide/NF3, CH4, C3H8. In order to obtain some qualitative estimation of aggregate size light scattering experiments were also performed on solutions of pyrazine/C3H8, benzene/CF4 benzene/NF3, and benzene/C3H8. The nature of these non-equilibrium molecular clusters in solution will be addressed.

  18. Hydrodynamic behavior of fractal aggregates

    NASA Astrophysics Data System (ADS)

    Wiltzius, Pierre

    1987-02-01

    Measurements of the radius of gyration RG and the hydrodynamic radius RH of colloidal silica aggregates are reported. These aggregates have fractal geometry and RH is proportional to RG for 500 Å<=RH<=7000 Å, with a ratio RH/RG=0.72+/-0.02. The results are compared with predictions for macromolecules of various shapes. The proportionality of the two radii can be understood with use of the pair correlation function of fractal objects and hydrodynamic interactions on the Oseen level. The value of the ratio remains to be explained.

  19. Effective intravenous immunoglobulin therapy for Churg-Strauss syndrome (allergic granulomatous angiitis) complicated by neuropathy of the eighth cranial nerve: a case report.

    PubMed

    Ozaki, Yoshio; Tanaka, Akihiro; Shimamoto, Keiko; Amuro, Hideki; Son, Yonsu; Ito, Tomoki; Nomura, Shosaku

    2012-09-18

    We report the case of a patient with Churg-Strauss syndrome with eighth cranial nerve palsy. Vestibulocochlear nerve palsy is extremely rare in Churg-Strauss syndrome. To the best of our knowledge, only one case of complicated neuropathy of the eighth cranial nerve has been described in a previous report presenting an aggregate calculation, but no differentiation between polyarteritis nodosa and Churg-Strauss syndrome was made. High-dose immunoglobulin was administered to our patient, and her neuropathy of the eighth cranial nerve showed improvement. At the age of 46, a Japanese woman developed Churg-Strauss syndrome that later became stable with low-dose prednisolone treatment. At the age of 52, she developed sudden difficulty of hearing in her left ear, persistent severe rotary vertigo, and mononeuritis multiplex. At admission, bilateral perceptive deafness of about 80dB and eosinophilia of 4123/μL in peripheral blood were found. A diagnosis of cranial neuropathy of the eighth cranial nerve associated with exacerbated Churg-Strauss syndrome was made. Although high doses of steroid therapy alleviated the inflammatory symptoms and markers, the vertigo and bilateral hearing loss remained. Addition of a high-dose immunoglobulin finally resulted in marked alleviation of the symptoms associated with neuropathy of the eighth cranial nerve. A high dose of immunoglobulin therapy shows favorable effects in neuropathy of the eighth cranial nerve, but no reports regarding its efficacy in cranial neuropathy have been published.

  20. Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits complicated by immunoglobulin A nephropathy in the renal allograft.

    PubMed

    Sawada, Anri; Kawanishi, Kunio; Horita, Shigeru; Koike, Junki; Honda, Kazuho; Ochi, Ayami; Komoda, Mizuki; Tanaka, Yoichiro; Unagami, Kohei; Okumi, Masayoshi; Shimizu, Tomokazu; Ishida, Hideki; Tanabe, Kazunari; Nagashima, Yoji; Nitta, Kosaku

    2016-07-01

    Immunoglobulin (Ig) A nephropathy (IgAN) is a known autoimmune disease due to abnormal glycosylation of IgA1, and occasionally, IgG co-deposition occurs. The prognosis of IgG co-deposition with IgAN is adverse, as shown in the previous studies. However, in the clinical setting, monoclonality of IgG co-deposition with IgAN has not been observed. We describe a case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) combined with IgAN in a renal allograft. A-21-year-old man developed end-stage renal failure with unknown aetiology and underwent living-donor kidney transplantation from his mother 2 years after being diagnosed. One year after kidney transplantation, proteinuria 2+ and haematuria 2+ were detected; allograft biopsy revealed mesangial IgA and C3 deposits, indicating a diagnosis of IgAN. After tonsillectomy and steroid pulse therapy, proteinuria and haematuria resolved. However, 4 years after transplantation, pedal oedema, proteinuria (6.89 g/day) and allograft dysfunction (serum creatinine (sCr) 203.3 µmol/L) appeared. A second allograft biopsy showed mesangial expansion and focal segmental proliferative endocapillary lesions with IgA1λ and monoclonal IgG1κ depositions. Electron microscopic analysis revealed a massive amount of deposits, located in the mesangial and subendothelial lesions. A diagnosis of PGNMID complicated with IgAN was made, and rituximab and plasmapheresis were added to steroid pulse therapy. With this treatment, proteinuria was alleviated to 0.5 g/day, and the allograft dysfunction recovered to sCr 132.6 µmol/L. This case suggests a necessity for investigation of PGNMID and IgA nephropathy in renal allografts to detect monoclonal Ig deposition disease.

  1. Renal involvement of monoclonal immunoglobulin deposition disease associated with an unusual monoclonal immunoglobulin A glycan profile.

    PubMed

    Kaneko, Syuzou; Usui, Joichi; Narimatsu, Yoshiki; Ito, Hiromi; Narimatsu, Hisashi; Hagiwara, Masahiro; Tsuruoka, Shuichi; Nagata, Michio; Yamagata, Kunihiro

    2010-08-01

    A 38-year-old man was admitted to the hospital for the evaluation of proteinuria, microscopic hematuria, and monoclonal IgA-kappa gammopathy. The initial renal pathological findings showed mesangial proliferative glomerulonephritis with endocapillary proliferation, a necrotizing lesion, and cellular crescent formation accompanied by IgA1-kappa deposition in the mesangium. Neither typical immune-complex deposits nor organized-structure deposits were detected. We diagnosed the patient with monoclonal immunoglobulin deposition disease (MIDD) associated with monoclonal IgA (mIgA). After the initiation of a monthly treatment with melphalan and predonisolone (MP therapy), the patient's serum IgA levels declined, and clinical remission was ultimately achieved. The follow-up renal biopsy showed reduced IgA-kappa staining, and both the endocapillary proliferation and the necrotizing lesion had disappeared. To elucidate the mechanism of IgA deposition, we investigated the glycan profile of the patient's serum mIgA using a mass spectrometry technique. The results revealed an unusual N-glycan profile compared to that of another patient with circulating mIgA lacking renal involvement and that of a healthy control. mIgA deposition in the mesangial area is a rare disease, and the glycan profiling of MIDD with renal involvement has not been reported previously. Thus, the present case suggests that any variation in Ig glycosylation may be a step in the pathogenesis of MIDD with renal involvement and/or contribute to some cases of IgA nephropathy.

  2. The association between immunoglobulin concentrations and prediabetes prevalence in a large Chinese cohort.

    PubMed

    Wang, Honglei; Song, Yanqi; Sun, Shaomei; Gao, Li; Liu, Li; Meng, Ge; Wu, Hongmei; Xia, Yang; Bao, Xue; Gu, Yeqing; Shi, Hongbin; Su, Qian; Fang, Liyun; Yang, Huijun; Wang, Xing; Zhou, Ming; Jia, Qiyu; Song, Kun; Zhang, Qing; Niu, Kaijun

    2017-08-01

    Prediabetes has received public attention owing to the increasing prevalence worldwide. Mounting evidence has indicated that inflammation directly contributed to the etiology of glucose metabolism disorders. Although immunoglobulins play a crucial role in immune responses, little research has been done on the link between immunoglobulins and prediabetes in adults. Hence, the aim of the present study was to explore the associations between immunoglobulins levels and prevalence of prediabetes in a general adult population. A cross-sectional study was conducted among 8856 adults (mean±standard deviation age: 48.4±10.7years) in Tianjin, China. The serum immunoglobulins concentrations were measured by the immunonephelometric technique. Prediabetes was diagnosed using the following parameters in accordance with the American Diabetes Association: fasting plasma glucose, postprandial glucose and glycosylated hemoglobin. The associations between concentrations of immunoglobulins and the prevalence of prediabetes were assessed using multiple logistic regression models. Overall, the prevalence of prediabetes was 37.4% (3311/8856). After controlling for confounders, compared with the lowest quintile, the odds ratios (95% confidence interval) of prediabetes for the highest quintile of immunoglobulins (immunoglobulin G, immunoglobulin E, immunoglobulin M and immunoglobulin A) were as follows: 1.06 (0.91-1.23), 1.31 (1.13-1.52), 0.86 (0.74-1.01), and 1.19 (1.03-1.38) (P for trend were 0.35, <0.0001, 0.04 and 0.02), respectively. Elevated immunoglobulin E and immunoglobulin A levels were independently and positively associated with prediabetes prevalence. There was also a trending association between immunoglobulin M concentrations and prediabetes prevalence. Further studies are necessary to clarify if there is a causal association of immunoglobulins in prediabetes or if they reflect early immunologic disturbances in these patients. Copyright © 2017 Elsevier Inc. All rights

  3. Normal human immunoglobulin G4 is bispecific: it has two different antigen-combining sites.

    PubMed

    Schuurman, J; Van Ree, R; Perdok, G J; Van Doorn, H R; Tan, K Y; Aalberse, R C

    1999-08-01

    Unlike other immunoglobulin G (IgG) subclasses, IgG4 antibodies in plasma have been reported to be functionally monovalent. In this paper we show that the apparent monovalency of circulating IgG4 is caused by asymmetry of plasma IgG4. A large fraction of plasma IgG4 molecules have two different antigen-binding sites, resulting in bispecificity. Sera from patients with IgG4 antibodies to both house dust mite and grass pollen induced cross-linking of Sepharose-bound grass pollen antigen to radiolabelled house dust mite allergen Der p I. This bispecific binding activity was not observed in sera with IgG4 antibodies to either grass pollen or house dust mite exclusively. Depletion of IgG4 antibodies resulted in disappearance of the bispecific activity. By size exclusion chromatography we excluded the possibility that bispecific activity was caused by aggregation of IgG4 antibodies. These results indicate that circulating (polyclonal) IgG4 antibodies have two different antigen-binding sites and therefore are functionally monovalent antibodies.

  4. A stacking flow immunoassay for the detection of dengue-specific immunoglobulins in salivary fluid.

    PubMed

    Zhang, Yi; Bai, Jianhao; Ying, Jackie Y

    2015-03-21

    Paper-based immunoassays, usually in the form of lateral flow tests, are currently the standard platform for home diagnostics. However, conventional lateral tests are often complicated by severe non-specific adsorption of detector particles when applied to test samples containing salivary fluid. It is believed that a high concentration of proteinaceous substances in salivary fluid causes particle aggregation and adhesion. In this study, we developed a stacking flow platform for single-step detection of a target antibody in salivary fluid. Stacking flow circumvents the need for separate sample pre-treatments, such as filtration or centrifugation, which are often required prior to testing saliva samples using paper-based immunoassays. This is achieved by guiding the samples and reagents to the test strip through different paths. By doing so, salivary substances that interfere with the particle-based sensing system are removed before they come into contact with the detection reagents, which greatly reduces the background. In addition, the stacking flow configuration enables uniform flow with a unique flow regulator, which leads to even test lines with good quantification capability, enabling the detection of ~20 ng mL(-1) α-fetoprotein in the serum. We have successfully applied the stacking flow device to detect dengue-specific immunoglobulins that are present in salivary fluid.

  5. Minipool Caprylic Acid Fractionation of Plasma Using Disposable Equipment: A Practical Method to Enhance Immunoglobulin Supply in Developing Countries

    PubMed Central

    El-Ekiaby, Magdy; Vargas, Mariángela; Sayed, Makram; Gorgy, George; Goubran, Hadi; Radosevic, Mirjana; Burnouf, Thierry

    2015-01-01

    Background Immunoglobulin G (IgG) is an essential plasma-derived medicine that is lacking in developing countries. IgG shortages leave immunodeficient patients without treatment, exposing them to devastating recurrent infections from local pathogens. A simple and practical method for producing IgG from normal or convalescent plasma collected in developing countries is needed to provide better, faster access to IgG for patients in need. Methodology/Principal Findings IgG was purified from 10 consecutive minipools of 20 plasma donations collected in Egypt using single-use equipment. Plasma donations in their collection bags were subjected to 5%-pH5.5 caprylic acid treatment for 90 min at 31°C, and centrifuged to remove the precipitate. Supernatants were pooled, then dialyzed and concentrated using a commercial disposable hemodialyzer. The final preparation was filtered online by gravity, aseptically dispensed into storage transfusion bags, and frozen at <-20°C. The resulting preparation had a mean protein content of 60.5 g/L, 90.2% immunoglobulins, including 83.2% IgG, 12.4% IgA, and 4.4% IgM, and residual albumin. There was fourfold to sixfold enrichment of anti-hepatitis B and anti-rubella antibodies. Analyses of aggregates (<3%), prekallicrein (5-7 IU/mL), plasmin (26.3 mU/mL), thrombin (2.5 mU/mL), thrombin-like activity (0.011 U/g), thrombin generation capacity (< 223 nM), and Factor XI (<0.01 U/mL) activity, Factor XI/XIa antigen (2.4 ng/g) endotoxin (<0.5 EU/mL), and general safety test in rats showed the in vitro safety profile. Viral validation revealed >5 logs reduction of HIV, BVDV, and PRV infectivity in less than 15 min of caprylic acid treatment. Conclusions/Significance 90% pure, virally-inactivated immunoglobulins can be prepared from plasma minipools using simple disposable equipment and bag systems. This easy-to-implement process could be used to produce immunoglobulins from local plasma in developing countries to treat immunodeficient patients

  6. Sporadic late onset nemaline myopathy and immunoglobulin deposition disease.

    PubMed

    Doppler, Kathrin; Knop, Stefan; Einsele, Hermann; Sommer, Claudia; Wessig, Carsten

    2013-12-01

    In monoclonal gammopathy, organ dysfunction can occur due to deposition of immunoglobulin fragments. A rare form of acquired myopathy often associated with monoclonal gammopathy is sporadic late onset nemaline myopathy (SLONM), which is characterized by nemaline rods in myofibers. The pathogenetic link between monoclonal gammopathy and SLONM has not yet been elucidated. Case report of a patient with monoclonal gammopathy who developed a progressive myopathy, finally diagnosed as SLONM. A muscle biopsy showed mild myopathic changes. A second biopsy 1 year after clinical onset demonstrated deposition of immunoglobulin light and heavy chains and the presence of nemaline rods. The patient experienced marked improvement of muscle strength after autologous stem cell transplantation and treatment with bortezomib, a therapy that is known to be effective in light chain deposition disease. We speculate that deposition of light and heavy chains, rather than nemaline bodies, has myotoxic effects on skeletal muscle. Copyright © 2013 Wiley Periodicals, Inc.

  7. Serum immunoglobulins and complement (C'3) in oral lichen planus.

    PubMed

    Sklavounou, A D; Laskaris, G; Angelopoulos, A P

    1983-01-01

    Serum immunoglobulins and complement (C'3) were determined by single radial immunodiffusion according to the method of Mancini and co-workers in fifty patients with oral lichen planus and twenty persons with clinically normal oral mucosa. Significantly increased levels of serum IgG (p less than 0.05) and a significant reduction of serum IgA concentration (p less than 0.05) in the experimental group as compared with normal controls were observed. Mean serum IgM and complement (C'3) levels were similar in patients and controls. No correlation between disease variety or extensiveness and immunoglobulin or complement levels was noticed. These results suggest that patients with oral lichen planus may have a generalized immunologic disorder in which humoral immunity is disturbed. Whether humoral immunity is of etiologic significance, contributes to the disease process, or, finally, represents an event secondary to the pathologic changes seen in the disease remains to be determined.

  8. Of ITIMs, ITAMs, and ITAMis: revisiting immunoglobulin Fc receptor signaling.

    PubMed

    Getahun, Andrew; Cambier, John C

    2015-11-01

    Receptors for immunoglobulin Fc regions play multiple critical roles in the immune system, mediating functions as diverse as phagocytosis, triggering degranulation of basophils and mast cells, promoting immunoglobulin class switching, and preventing excessive activation. Transmembrane signaling associated with these functions is mediated primarily by two amino acid sequence motifs, ITAMs (immunoreceptor tyrosine-based activation motifs) and ITIMs (immunoreceptor tyrosine-based inhibition motifs) that act as the receptors' interface with activating and inhibitory signaling pathways, respectively. While ITAMs mobilize activating tyrosine kinases and their consorts, ITIMs mobilize opposing tyrosine and inositol-lipid phosphatases. In this review, we will discuss our current understanding of signaling by these receptors/motifs and their sometimes blurred lines of function.

  9. Immunoglobulin concentrations in human tears in ocular diseases.

    PubMed Central

    Sen, D K; Sarin, G S

    1979-01-01

    Immunoglobulin concentrations in human tears were determined in 165 patients with different eye diseases by a standard radial immunodiffusion method. IgA was present in all the samples in measurable quantity. The mean IgA values were significantly higher than the controls in patients with acute bacterial conjunctivitis, keratomalacia, corneal graft reaction, blepharoconjunctivitis, and acute keratoconjunctivitis. The values in the patients with vernal conjunctivitis, phlyctenular conjunctivitis, acute bacterial corneal ulcer, and acute endogenous uveitis were not significantly different from those in the controls. IgG could be detected in the majority of the samples but it was in measurable quantity in 18 samples. IgM could be detected in fewer samples. IgD was not detected in any of them. The study indicates that, whenever the immunoglobulin levels in tears are altered in diseased eyes, it is the IgA level that is predominantly altered and not the IgG level. PMID:465402

  10. The immunoglobulin heavy chain locus in the reptile Anolis carolinensis.

    PubMed

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

    2009-05-01

    We describe the entire immunoglobulin heavy chain (IgH) locus from the reptile Anolis carolinensis. The heavy chain constant (C(H)) region includes C mu, C delta and C upsilon genes. This is the first description of a C upsilon gene in the reptilian class. Variable (V(H)), diversity (D(H)) and joining (J(H)) genes are located 5' from the constant (C(H)) chain complex locus. The C mu and C upsilon genes encode antibodies with four immunoglobulin domains. The C delta gene encoded an 11 domain delta heavy chain as in Eublepharis macularius. Seventy V(H) genes, belonging to 28 families, were identified, and they can be sorted into five broader groups. The similarity of the organization of the reptilian genes with those of amphibians and mammals suggests the existence of a process of heavy chain genomic reorganization before the radiation of tetrapod vertebrates.

  11. Fc glycan-modulated immunoglobulin G effector functions.

    PubMed

    Quast, Isaak; Lünemann, Jan D

    2014-07-01

    Immunoglobulin G (IgG) molecules are glycoproteins and residues in the sugar moiety attached to the IgG constant fragment (Fc) are essential for IgG functionality such as binding to cellular Fc receptors and complement activation. The core of this sugar moiety consists of a bi-antennary heptameric structure of mannose and N-acetylglucosamine (GlcNAc), further decorated with terminal and branching residues including galactose, sialic acid, fucose, and GlcNAc. Presence or absence of distinct residues such as fucose and sialic acid can dramatically alter pro- and anti-inflammatory IgG activities which could be harnessed for immunotherapeutic purposes. Here we review recent advances in understanding the role of the IgG-Fc glycan during immune responses and for immunotherapy with a focus on sialic acid and intravenous immunoglobulin (IVIG) treatment.

  12. Immunoglobulin concentrations in human tears in ocular diseases.

    PubMed

    Sen, D K; Sarin, G S

    1979-05-01

    Immunoglobulin concentrations in human tears were determined in 165 patients with different eye diseases by a standard radial immunodiffusion method. IgA was present in all the samples in measurable quantity. The mean IgA values were significantly higher than the controls in patients with acute bacterial conjunctivitis, keratomalacia, corneal graft reaction, blepharoconjunctivitis, and acute keratoconjunctivitis. The values in the patients with vernal conjunctivitis, phlyctenular conjunctivitis, acute bacterial corneal ulcer, and acute endogenous uveitis were not significantly different from those in the controls. IgG could be detected in the majority of the samples but it was in measurable quantity in 18 samples. IgM could be detected in fewer samples. IgD was not detected in any of them. The study indicates that, whenever the immunoglobulin levels in tears are altered in diseased eyes, it is the IgA level that is predominantly altered and not the IgG level.

  13. [Optimization of gel radial diffusion method for serum immunoglobulin analysis].

    PubMed

    Gerasimov, I G; Zorkova, E V

    2002-07-01

    Serum IgA, IgM, and IgG were measured by radial immunodiffusion in gel; immunoglobulin concentrations correlated with the diameter of their diffusion. A theoretically-based equation was derived; use of this equation will help estimate serum Ig content without plotting a calibration curve by the square diameter of the immunodiffusion ring of undiluted reference serum in a wide range of concentrations (0.3-3 mg/ml for IgA and IgM and 2-18 mg/ml for IgG). This modification of measuring serum immunoglobulins by radial immunodiffusion in gel is as accurate as other methods, but is reagent- and time-saving.

  14. [Subcutaneous immunoglobulin. Treatment in chronic inflammatory demyelinating polyradiculo-neuropathy].

    PubMed

    Nogués, Martín A; Varela, Francisco J; Seminario, Gisela; Insúa, María C; Bezrodnik, Liliana

    2016-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired disease that may affect nerve roots and peripheral nerves. Despite its low incidence, diagnosis is particularly important because there are different effective treatments. Human immunoglobulin is one of the mainstays of the treatment. Although there are few studies up to date, subcutaneous immunoglobulin (IgSC) has been proposed as an alternative to intravenous administration with similar efficacy. We present three cases with definite CIDP, classified according to the European Federation of Neurological Societies / Peripheral Nerve, Society (EFNS /PNS) criteria in which was used SCIgG as a treatment after success with the intravenous route. The Overall Neuropathy Limitations Scale (ONLS) was used to estimate the changes in the muscular strength before and after treatment.

  15. Complete nucleotide sequence of primitive vertebrate immunoglobulin light chain genes.

    PubMed Central

    Shamblott, M J; Litman, G W

    1989-01-01

    Antibody to Heterodontus francisci (horned shark) immunoglobulin light chain was used to screen a spleen cDNA expression library, and recombinant clones encoding light chain genes were isolated. The complete sequences of the mature coding regions of two light chain genes in this phylogenetically distant vertebrate have been determined and are reported here. Comparisons of the sequences are consistent with the presence of mammalian-like framework and complementarity-determining regions. The predicted amino acid sequences of the genes are more related to mammalian lambda than to kappa light chains. The nucleotide sequences of the genes are most related to mammalian T-cell antigen receptor beta chain. Heterodontus light chain genes may reflect characteristics of the common ancestor of immunoglobulin and T-cell antigen receptors before its evolutionary diversification. PMID:2499889

  16. Complete nucleotide sequence of primitive vertebrate immunoglobulin light chain genes.

    PubMed

    Shamblott, M J; Litman, G W

    1989-06-01

    Antibody to Heterodontus francisci (horned shark) immunoglobulin light chain was used to screen a spleen cDNA expression library, and recombinant clones encoding light chain genes were isolated. The complete sequences of the mature coding regions of two light chain genes in this phylogenetically distant vertebrate have been determined and are reported here. Comparisons of the sequences are consistent with the presence of mammalian-like framework and complementarity-determining regions. The predicted amino acid sequences of the genes are more related to mammalian lambda than to kappa light chains. The nucleotide sequences of the genes are most related to mammalian T-cell antigen receptor beta chain. Heterodontus light chain genes may reflect characteristics of the common ancestor of immunoglobulin and T-cell antigen receptors before its evolutionary diversification.

  17. Intravenous Immunoglobulin in the Management of Lupus Nephritis

    PubMed Central

    Wenderfer, Scott E.; Thacker, Trisha

    2012-01-01

    The occurrence of nephritis in patients with systemic lupus erythematosus is associated with increased morbidity and mortality. The pathogenesis of lupus nephritis is complex, involving innate and adaptive cellular and humoral immune responses. Autoantibodies in particular have been shown to be critical in the initiation and progression of renal injury, via interactions with both Fc-receptors and complement. One approach in the management of patients with lupus nephritis has been the use of intravenous immunoglobulin. This therapy has shown benefit in the setting of many forms of autoantibody-mediated injury; however, the mechanisms of efficacy are not fully understood. In this paper, the data supporting the use of immunoglobulin therapy in lupus nephritis will be evaluated. In addition, the potential mechanisms of action will be discussed with respect to the known involvement of complement and Fc-receptors in the kidney parenchyma. Results are provocative and warrant additional clinical trials. PMID:23056926

  18. Studies on recycled aggregates-based concrete.

    PubMed

    Rakshvir, Major; Barai, Sudhirkumar V

    2006-06-01

    Reduced extraction of raw materials, reduced transportation cost, improved profits, reduced environmental impact and fast-depleting reserves of conventional natural aggregates has necessitated the use of recycling, in order to be able to conserve conventional natural aggregate. In this study various physical and mechanical properties of recycled concrete aggregates were examined. Recycled concrete aggregates are different from natural aggregates and concrete made from them has specific properties. The percentages of recycled concrete aggregates were varied and it was observed that properties such as compressive strength showed a decrease of up to 10% as the percentage of recycled concrete aggregates increased. Water absorption of recycled aggregates was found to be greater than natural aggregates, and this needs to be compensated during mix design.

  19. RAGG - R EPISODIC AGGREGATION PACKAGE

    EPA Science Inventory

    The RAGG package is an R implementation of the CMAQ episodic model aggregation method developed by Constella Group and the Environmental Protection Agency. RAGG is a tool to provide climatological seasonal and annual deposition of sulphur and nitrogen for multimedia management. ...

  20. Mesoscale Simulation of Asphaltene Aggregation.

    PubMed

    Wang, Jiang; Ferguson, Andrew L

    2016-08-18

    Asphaltenes constitute a heavy aromatic crude oil fraction with a propensity to aggregate and precipitate out of solution during petroleum processing. Aggregation is thought to proceed according to the Yen-Mullins hierarchy, but the molecular mechanisms underlying mesoscopic assembly remain poorly understood. By combining coarse-grained molecular models parametrized using all-atom data with high-performance GPU hardware, we have performed molecular dynamics simulations of the aggregation of hundreds of asphaltenes over microsecond time scales. Our simulations reveal a hierarchical self-assembly mechanism consistent with the Yen-Mullins model, but the details are sensitive and depend on asphaltene chemistry and environment. At low concentrations asphaltenes exist predominantly as dispersed monomers. Upon increasing concentration, we first observe parallel stacking into 1D rod-like nanoaggregates, followed by the formation of clusters of nanoaggregates associated by offset, T-shaped, and edge-edge stacking. Asphaltenes possessing long aliphatic side chains cannot form nanoaggregate clusters due to steric repulsions between their aliphatic coronae. At very high concentrations, we observe a porous percolating network of rod-like nanoaggregates suspended in a sea of interpenetrating aliphatic side chains with a fractal dimension of ∼2. The lifetime of the rod-like aggregates is described by an exponential distribution reflecting a dynamic equilibrium between coagulation and fragmentation.

  1. RAGG - R EPISODIC AGGREGATION PACKAGE

    EPA Science Inventory

    The RAGG package is an R implementation of the CMAQ episodic model aggregation method developed by Constella Group and the Environmental Protection Agency. RAGG is a tool to provide climatological seasonal and annual deposition of sulphur and nitrogen for multimedia management. ...

  2. Sequence-dependent internalization of aggregating peptides.

    PubMed

    Couceiro, José R; Gallardo, Rodrigo; De Smet, Frederik; De Baets, Greet; Baatsen, Pieter; Annaert, Wim; Roose, Kenny; Saelens, Xavier; Schymkowitz, Joost; Rousseau, Frederic

    2015-01-02

    Recently, a number of aggregation disease polypeptides have been shown to spread from cell to cell, thereby displaying prionoid behavior. Studying aggregate internalization, however, is often hampered by the complex kinetics of the aggregation process, resulting in the concomitant uptake of aggregates of different sizes by competing mechanisms, which makes it difficult to isolate pathway-specific responses to aggregates. We designed synthetic aggregating peptides bearing different aggregation propensities with the aim of producing modes of uptake that are sufficiently distinct to differentially analyze the cellular response to internalization. We found that small acidic aggregates (≤500 nm in diameter) were taken up by nonspecific endocytosis as part of the fluid phase and traveled through the endosomal compartment to lysosomes. By contrast, bigger basic aggregates (>1 μm) were taken up through a mechanism dependent on cytoskeletal reorganization and membrane remodeling with the morphological hallmarks of phagocytosis. Importantly, the properties of these aggregates determined not only the mechanism of internalization but also the involvement of the proteostatic machinery (the assembly of interconnected networks that control the biogenesis, folding, trafficking, and degradation of proteins) in the process; whereas the internalization of small acidic aggregates is HSF1-independent, the uptake of larger basic aggregates was HSF1-dependent, requiring Hsp70. Our results show that the biophysical properties of aggregates determine both their mechanism of internalization and proteostatic response. It remains to be seen whether these differences in cellular response contribute to the particular role of specific aggregated proteins in disease.

  3. Altered secretory immunoglobulin A on skin surface after intensive exercise.

    PubMed

    Eda, Nobuhiko; Shimizu, Kazuhiro; Suzuki, Satomi; Tanabe, Yoko; Lee, Eunjae; Akama, Takao

    2013-09-01

    The aim of this study was to determine the effects of high-intensity endurance exercise on skin immunity by estimating secretory immunoglobulin A (SIgA) and staphylococci on skin surface. Seven healthy adult men (age, 22.3 ± 2.0 years) performed bicycle exercise at 75% HRmax for 60 minutes from 2030 to 2130 hours. Secretory immunoglobulin A was obtained from 1 ml extraction liquids stirred with the microtube homogenizer in the open end of a polypropylene tube for 60 seconds. Secretory immunoglobulin A concentrations were measured using enzyme-linked immunosorbent assay. Staphylococci were harvested by pressed agar-based media against skin surface. Skin surface samples were collected from the chest and the forearm on the first day at 2030 hours (before rest, A1), 2130 hours (after rest, A2), and 2230 hours (after showering, A3); the next morning at 0700 hours (A4); on the second day at 2030 hours (before exercise, B1), 2130 hours (after exercise, B2), and 2230 hours (after showering, B3); and the next morning at 0700 hours (B4). Secretory immunoglobulin A concentration on the forearm was significantly lower at B2 (p < 0.05) and B3 (p < 0.05) than that at B1 and that on the chest at B1 tended to be higher compared with B2 (p = 0.084) and B3 (p = 0.075). The number of staphylococci was significantly higher at B2 than that at B1 (p < 0.01) and B4 (p < 0.01) on the forearm. We conclude that high-intensity endurance exercise might depress immune function and enhance infectious risk on skin surface. Coaches should encourage their athletes to take a shower and change into clean clothes immediately after sports activities and athletes should maintain a clean skin surface to decrease the infectious risk on skin surface.

  4. Role of systemic injection of rabies immunoglobulin in rabies vaccination.

    PubMed

    Wu, Weichen; Liu, Shuqing; Yu, Pengcheng; Tao, Xiaoyan; Lu, Xuexin; Yan, Jianghong; Wang, Qian; Zhang, Zongshen; Zhu, Wuyang

    2017-06-01

    To determine the role of systemic injection of rabies immunoglobulin (RIG) in rabies vaccination, we analyzed the level of antibody against rabies virus in the serum of mice that received various doses of RIG combined with rabies vaccine. Our results indicate that systemic injection of RIG does not contribute detectably to passive or adaptive immunization, suggesting that the main function of RIG in individuals with category III exposure is to neutralize rabies virus via immediate local infiltration of the wound.

  5. [INTRAVENOUS INJECTION OF IMMUNOGLOBULINS IN CHILDREN, SUFFERING SEPSIS].

    PubMed

    Yachnyk, I M; Karpenko, N P; Antyukhin, S V; Klubuk, I M; Tryliska, T V; Mehlnyk, V A

    2016-01-01

    The efficacy of normal immunoglobulin of a man (NIM) injection in children, suffering sepsis and being in extremely severe state, was studied. Of 174 patients, who were treated for sepsis in 2005 - 2014 yrs., in 69 (39.6%)--NIM was applied, in 105 (60.3%)--did not apply. Positive changes of cellular immunity while immunotherapy application were noted. To estimate the immunotherapy efficacy it is mandatory to continue investigations with recruiting more quantity of patients.

  6. [Importance of immunoglobulins and nutrition in infections in neonates].

    PubMed

    Colić-Hadzić, Belkisa; Tahirović, Husref

    2004-01-01

    The purpose of the study was an estimation of the immunoglobulin serum and the way of nutrition of a new-born child at the beginning of bacterial infections during the first month of life. 120 new-born children (infantiles) of both sexes was prospectively studied, who were born in the Gynecology-obstetrician clinic in Tuzla, in the period from March-May 2000 year. On the base of mothers SES during the pregnancy, new-born children were separated in two groups. Group A was formed of 60 new-born children (32 female and 28 male), mothers had good SES during the pregnancy, and concentration of serum immunoglobulin G (IgG) examined from cords blood, from 10.02 to 17.58 g/L (X 14.48 g/L +/- 1.87). Group B was formed of 60 new-born children (27 female and 33 male), with bad mothers SES and with concentration of IgG from 6.80 to 13.01 g/L (X 10.62 g/L +/- 1.49). Immunoglobulins M and immunoglobulins A were negative in both groups of children. During the first month of life it was studied the way of nutrition and health condition of each new-born child. New-born children with bad mothers SES during the pregnancy, with low values of IgG and who were on the artificial food (nutrition), were showing with the significant difference (p < 0.001) in bacterial infections, comparing with the group who had good IgG. The new-born children with natural nutrition, despite the lower concentration of IgG, were protected from severe bacterial infections.

  7. Intracellular Neutralization of Virus by Immunoglobulin A Antibodies

    NASA Astrophysics Data System (ADS)

    Mazanec, Mary B.; Kaetzel, Charlotte S.; Lamm, Michael E.; Fletcher, David; Nedrud, John G.

    1992-08-01

    IgA is thought to neutralize viruses at the epithelial surface of mucous membranes by preventing their attachment. Since IgA, a polymeric immunoglobulin, is transported through the lining of epithelial cells by the polymeric-immunoglobulin receptor and since viruses are obligate intracellular parasites, we hypothesized that IgA antibodies may also interfere with viral replication by binding to newly synthesized viral proteins within infected cells. Polarized monolayers of Madin-Darby canine kidney epithelial cells expressing the polymeric-immunoglobulin receptor were infected on the apical surface with Sendai virus. Anti-Sendai virus IgA monoclonal antibody delivered from the basolateral surface colocalized with viral protein within the cell, as documented by immunofluorescence. More importantly, anti-viral IgA reduced virus titers >1000-fold (P < 0.0001) in apical supernatants and >10-fold (P < 0.0001) in cell lysates from monolayers treated with anti-viral IgA compared with those treated with either anti-viral IgG or an irrelevant IgA monoclonal antibody. We believe that the differences in viral titers between cell layers treated with specific IgA, which enters the epithelial cell by binding to the polymeric-immunoglobulin receptor, and those treated with specific IgG, which does not enter the cells, or irrelevant IgA indicate that specific intracellular IgA antibodies can inhibit viral replication. Thus, in addition to the classical role of humoral antibodies in extracellular defense, IgA antibody may be able to neutralize microbial pathogens intracellularly, giving IgA a role in host defense that has traditionally been reserved for cell-mediated immunity.

  8. CD147 Immunoglobulin Superfamily Receptor Function and Role in Pathology

    PubMed Central

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

    2008-01-01

    The immunoglobulin superfamily member CD147 plays an important role in fetal, neuronal, lymphocyte and extracellular matrix development. Here we review the current understanding of CD147 expression and protein interactions with regard to CD147 function and its role in pathologic conditions including heart disease, Alzheimer’s disease, stroke and cancer. A model linking hypoxic conditions found within the tumor microenvironment to up-regulation of CD147 expression and tumor progression is introduced. PMID:17945211

  9. Serum immunoglobulin G levels and peritonitis in peritoneal dialysis patients.

    PubMed

    Courivaud, Cécile; Bardonnet, Karine; Crepin, Thomas; Bresson-Vautrin, Catherine; Rebibou, Jean-Michel; Ducloux, Didier

    2015-08-01

    Peritonitis is a frequent and serious complication of peritoneal dialysis (PD). Whether low immunoglobulin level is associated with PD-related peritonitis is unknown. We conducted a prospective study to assess whether immunoglobulin levels at PD onset could predict the occurrence of peritonitis. All patients starting peritoneal dialysis between 01/2005 and 12/2010 at the University hospital of Besançon, France, were included in the study. Of 240 consecutive PD patients enrolled (mean follow-up 25 ± 12 months), 76 (32%) had at least one episode of peritonitis. Mean immunoglobulin (Ig)G level at PD start was lower in patients who subsequently experienced peritonitis (7.9 + 3.4 vs. 9.7 + 3.4 g/l, p = 0.005). An increased IgG level at PD onset was associated with a reduced risk of peritonitis [hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.80-0.97 for each increase of 1 g/l in IgG, p = 0.008]. IgG level ≤6.4 g/l ("low IgG") was the best predictive value for the occurrence of subsequent peritonitis: 52 patients (24%) had low IgG levels. At multivariate analysis, both low IgG level (HR 2.49, 95% CI 1.32-4.69, p = 0.005) and diabetes (HR 2.78, 95% CI 1.49-5.20, p = 0.001) were predictive of the occurrence of peritonitis. Low IgG levels predict the occurrence of PD-related peritonitis. Randomized studies should determine whether such patients could benefit from intravenous immunoglobulin administration.

  10. Small quantities of erythrocyte bound immunoglobulins and autoimmune haemolysis.

    PubMed Central

    Sokol, R J; Hewitt, S; Booker, D J; Stamps, R

    1987-01-01

    Enzyme linked and radioimmune direct antiglobulin tests (DAGTs) were used to assess red cell bound IgG, IgA, and IgM in 585 patients referred to an immunohaematology reference centre. One hundred and fifty eight patients with less than or equal to 200 mol IgG and small amounts of IgA and IgM coating their red cells were studied in detail. The presence of autoimmune haemolysis was determined from the clinical, haematological, and biochemical findings; it occurred in at least 25% of the 158 patients, the degree varying widely. There was a highly significant association between small increases in cell bound immunoglobulins and the presence of autoimmune haemolysis. Immunoglobulins of IgG, IgA, and IgM classes could produce autoimmune haemolysis when the classical agglutination DAGTs were negative; the IgA and IgM were usually found in association with IgG. The haemolytic effect was enhanced by the presence of complement and combinations of immunoglobulin classes on the red cells. PMID:3558858

  11. Endogenous immunoglobulins and sepsis: New perspectives for guiding replacement therapies.

    PubMed

    Bermejo-Martin, Jesús F; Giamarellos-Bourboulis, Evangelos J

    2015-12-01

    The recently emerging concept of immunosuppression developing in the field of severe sepsis generated the need to measure circulating immunoglobulins as part of the necessary tests to evaluate immunocompetence status in patients suffering from this condition. Serum concentrations can be used as a surrogate marker of the final outcome and as a biomarker to explore the need for supplementation of the host with intravenous immunoglobulin preparations. Available evidence from recent clinical studies pinpoints the main observations. The first is that circulating IgM is a phenomenon associated with progression from severe sepsis to septic shock. Deficient kinetics of circulating IgM during the first 7 days following the start of vasopressors is linked with unfavourable outcome. The second is the development of immunoscores using low levels of IgM, IgG1 and IgA. These immunoscores can predict 28-day mortality with an odds ratio ranging between 3 and 5. Novel techniques for evaluating patient's immune status are shedding new light on the development of modern therapeutics where immunoglobulin replacement may be part of a personalised therapeutic approach.

  12. Immunoglobulin Cmu RNA in T lymphoma cells is not translated.

    PubMed

    Walker, I D; Harris, A W

    1980-11-20

    It is widely believed that immunoglobulin genes might encode at least part of the receptor for antigen on the T lymphocyte. Evidence supporting this comes from the effects of anti-immunoglobulin idiotype antibodies on cellular immune networks and from the presence of idiotypes on immunologically active factors from T cells. Detailed molecular characterization of the receptors, however, has been seriously hampered by the lack of a suitable cellular source from which it might be isolated. The recent demonstration of Kemp et al. that thymocytes and certain cultured lines of mouse T lymphoma cells contain polyadenylated RNA molecules encoded by the immunoglobulin Cmu gene (Cmu RNA) prompted us to identify the corresponding protein molecules in those cells. As the haploid mouse genome contains a single Cmu gene, any polypeptide encoded by this gene should react with at least some of the antibodies present in rabbit anti-mouse IgM antiserum. In this letter we report that a number of T lymphoma lines, regardless of whether they contain Cmu RNA, synthesize no detectable mu polypeptides.

  13. Prophylactic intravenous immunoglobulin injections to mothers with primary cytomegalovirus infection.

    PubMed

    Tanimura, Kenji; Tairaku, Shinya; Deguchi, Masashi; Sonoyama, Ayako; Morizane, Mayumi; Ebina, Yasuhiko; Morioka, Ichiro; Yamada, Hideto

    2014-07-11

    The aim of this trial study was to assess the preventive efficacy of immunoglobulin with a high titer of anti-CMV antibody for mother-to-fetus cytomegalovirus (CMV) transmission among pregnant women with primary/acute CMV infection. The primary CMV infection in mothers was diagnosed by a positive test for CMV IgM and/or low IgG avidity. Intact type immunoglobulin with a high titer of anti-CMV antibody was injected intravenously at a dosage of 2.5-5.0 g/day for consecutive 3 days to mothers with primary CMV infection. Four pregnant women were enrolled. One pregnancy ended in no congenital infection, while two pregnancies ended in congenital CMV infection. The other one pregnancy was terminated. The mother-to-fetus CMV transmission rate was found to be high as 66.7% (2/3). This preliminary result suggests that intravenous immunoglobulin injections are not effective for the prevention of mother-to-fetus CMV transmission in the present protocol.

  14. Polyomavirus BK Neutralizing Activity in Human Immunoglobulin Preparations

    PubMed Central

    Randhawa, Parmjeet S; Schonder, Kristine; Shapiro, Ron; Farasati, Nousha; Huang, Yuchen

    2011-01-01

    Background Polyomavirus BK (BKV) infection can cause nephropathy in the allograft kidney. No well-established drug treatment is available at this time. Human intravenous immunoglobulins (IVIG) have been used as an empiric therapy without proof of effectiveness. Methods We tested five lots of commercially available IVIG preparations from two different suppliers for polyomavirus neutralizing activity. BKV and mouse polyomavirus were used to infect human and murine host cells, respectively, with or without prior treatment with IVIG. Neutralization activity was measured by quantitation of viral DNA after 7 days in culture. Results Coincubation of BKV but not mouse polyomavirus with clinically relevant concentrations of IVIG derived from healthy and hepatitis B vaccinated subjects caused more than 90% inhibition of viral DNA yield after 7 days in culture. Consistent with a direct neutralizing mechanism, this effect was significantly diminished if viral infection was performed in immunoglobulin pretreated cells or if immunoglobulin treatment was delayed 2 hr after addition of infectious virus. Conclusion Human IVIG preparations contain BKV neutralizing antibodies. Data on neutralizing capacity of these antibodies are presented to aid dose exploration in clinical trials seeking to validate the use of IVIG in patients with BKV infection. PMID:20568674

  15. Regulation of immunoglobulin secretion by factor H of human complement.

    PubMed Central

    Tsokos, G C; Inghirami, G; Tsoukas, C D; Balow, J E; Lambris, J D

    1985-01-01

    As human B lymphocytes and macrophages carry surface receptors for Factor H (B1H), we investigated the possibility that this complement component regulates their function. Factor H inhibits immunoglobulin secretion by peripheral mononuclear cells (MNC) stimulated with pokeweed mitogen if present at the initiation of the cultures and at concentrations greater than 50 micrograms/ml. Factor H also inhibited stimulation and differentiation of purified B cells into immunoglobulin-secreting cells by Epstein-Barr virus (EBV). The inhibitory effect of Factor H was abrogated if anti-Factor H antibody was present in the cultures. EBV-transformed B-cell lines secreted less immunoglobulin if Factor H was present in the culture for at least 4 days. Culture of MNC with Factor H did not lead to the generation of suppressor T cells or macrophages. In contrast, Factor H did not cause proliferation of human peripheral total MNC or enriched T-cell or B-cell subpopulations. Also, Factor H did not inhibit the proliferation of MNC in response to several mitogens and antigens. Our results strongly indicate that Factor H is able to block human B-cell differentiation in vitro without blocking the proliferative ability of the cells. Factor H seems to act directly on the B cells through its receptor on their surface, since it inhibited T-dependent and T-independent B-cell differentiation but generated no suppressor cells. Images Figure 1 PMID:2991125

  16. Regulation of immunoglobulin secretion by factor H of human complement.

    PubMed

    Tsokos, G C; Inghirami, G; Tsoukas, C D; Balow, J E; Lambris, J D

    1985-07-01

    As human B lymphocytes and macrophages carry surface receptors for Factor H (B1H), we investigated the possibility that this complement component regulates their function. Factor H inhibits immunoglobulin secretion by peripheral mononuclear cells (MNC) stimulated with pokeweed mitogen if present at the initiation of the cultures and at concentrations greater than 50 micrograms/ml. Factor H also inhibited stimulation and differentiation of purified B cells into immunoglobulin-secreting cells by Epstein-Barr virus (EBV). The inhibitory effect of Factor H was abrogated if anti-Factor H antibody was present in the cultures. EBV-transformed B-cell lines secreted less immunoglobulin if Factor H was present in the culture for at least 4 days. Culture of MNC with Factor H did not lead to the generation of suppressor T cells or macrophages. In contrast, Factor H did not cause proliferation of human peripheral total MNC or enriched T-cell or B-cell subpopulations. Also, Factor H did not inhibit the proliferation of MNC in response to several mitogens and antigens. Our results strongly indicate that Factor H is able to block human B-cell differentiation in vitro without blocking the proliferative ability of the cells. Factor H seems to act directly on the B cells through its receptor on their surface, since it inhibited T-dependent and T-independent B-cell differentiation but generated no suppressor cells.

  17. Comprehensive N-Glycan Profiling of Avian Immunoglobulin Y

    PubMed Central

    Millán Martín, Silvia; Wormald, Mark R.; Zapatero-Rodríguez, Julia; Conroy, Paul J.; O’Kennedy, Richard J.; Rudd, Pauline M.; Saldova, Radka

    2016-01-01

    Recent exploitation of the avian immune system has highlighted its suitability for the generation of high-quality, high-affinity antibodies to a wide range of antigens for a number of therapeutic and biotechnological applications. The glycosylation profile of potential immunoglobulin therapeutics is species specific and is heavily influenced by the cell-line/culture conditions used for production. Hence, knowledge of the carbohydrate moieties present on immunoglobulins is essential as certain glycan structures can adversely impact their physicochemical and biological properties. This study describes the detailed N-glycan profile of IgY polyclonal antibodies from the serum of leghorn chickens using a fully quantitative high-throughput N-glycan analysis approach, based on ultra-performance liquid chromatography (UPLC) separation of released glycans. Structural assignments revealed serum IgY to contain complex bi-, tri- and tetra-antennary glycans with or without core fucose and bisects, hybrid and high mannose glycans. High sialic acid content was also observed, with the presence of rare sialic acid structures, likely polysialic acids. It is concluded that IgY is heavily decorated with complex glycans; however, no known non-human or immunogenic glycans were identified. Thus, IgY is a potentially promising candidate for immunoglobulin-based therapies for the treatment of various infectious diseases. PMID:27459092

  18. The thermal aggregation of ovalbumin as large particles decreases its allergenicity for egg allergic patients and in a murine model.

    PubMed

    Claude, M; Lupi, R; Bouchaud, G; Bodinier, M; Brossard, C; Denery-Papini, S

    2016-07-15

    Most egg-allergic children can tolerate extensively cooked eggs. Ovalbumin, a major allergen in egg whites, is prone to aggregate upon heating. This study compares ovalbumin's allergenicity when it is aggregated as large particles to ovalbumin in its native form. Immunoglobulins (Ig)-binding and the degranulation capacities of native and aggregated ovalbumin were measured with sera from egg-allergic children and from mice sensitized to native or aggregated ovalbumin. The influence of ovalbumin structure on Ig production upon sensitization and elicitation potency by challenge was also studied. We showed that heat aggregation of ovalbumin as large particles enhances IgG production and promotes IgG2a production (a shift toward the T helper 1 profile). Aggregated ovalbumin displayed lower Ig-binding and basophil-activation capacities for sera from both allergic patients and mice. This work illustrates the links between ovalbumin structure after heating and allergenicity potential using parameters from both the sensitization and elicitation phases of the allergic reaction. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. CEACAM1 mediates B cell aggregation in central nervous system autoimmunity

    PubMed Central

    Rovituso, Damiano M.; Scheffler, Laura; Wunsch, Marie; Dörck, Sebastian; Ulzheimer, Jochen; Bayas, Antonios; Steinman, Lawrence; Ergün, Süleyman; Kuerten, Stefanie

    2016-01-01

    B cell aggregates in the central nervous system (CNS) have been associated with rapid disease progression in patients with multiple sclerosis (MS). Here we demonstrate a key role of carcinoembryogenic antigen-related cell adhesion molecule1 (CEACAM1) in B cell aggregate formation in MS patients and a B cell-dependent mouse model of MS. CEACAM1 expression was increased on peripheral blood B cells and CEACAM1+ B cells were present in brain infiltrates of MS patients. Administration of the anti-CEACAM1 antibody T84.1 was efficient in blocking aggregation of B cells derived from MS patients. Along these lines, application of the monoclonal anti-CEACAM1 antibody mCC1 was able to inhibit CNS B cell aggregate formation and significantly attenuated established MS-like disease in mice in the absence of any adverse effects. CEACAM1 was co-expressed with the regulator molecule T cell immunoglobulin and mucin domain −3 (TIM-3) on B cells, a novel molecule that has recently been described to induce anergy in T cells. Interestingly, elevated coexpression on B cells coincided with an autoreactive T helper cell phenotype in MS patients. Overall, these data identify CEACAM1 as a clinically highly interesting target in MS pathogenesis and open new therapeutic avenues for the treatment of the disease. PMID:27435215

  20. Phylogeny of immunoglobulin structure and function. VII. Monomeric and tetrameric immunoglobulins of the margate, a marine teleost fish.

    PubMed Central

    Clem, L W; McLean, W E

    1975-01-01

    The margate, a marine teleost fish, was found to contain both high (16S) and low (7S) molecular weight antibodies 17 days after initial immunization. The 16S antibodies were detectable with both haemagglutination and antigen-binding assays, whereas the 7S antibodies were only detected by the latter technique. Margate 16S (molecular weight approximately 700,000) and 7S (molecular weight approximately 175,000) immunoglobulins were isolated and shown to be antigenically indistinguishable. They therefore appear to belong to the same immunoglobulin class and to have a tetramer--monomer relationship. Experiments with stored sera indicated the 7S protein is probably not an in vitro degradation product of the 16S molecule. Images FIG. 3 FIG. 4 PMID:1184121

  1. WITHDRAWN: Immunoglobulin treatment for respiratory syncytial virus infection.

    PubMed

    Fuller, Hannah L; Del Mar, Chris B

    2010-09-08

    Respiratory syncytial virus (RSV) bronchiolitis and pneumonia hospitalise hundreds of thousands of infants every year. Treatment is largely supportive therapy, (for example, oxygen, fluids and occasionally mechanical ventilation). Ribavirin, an antiviral agent, is licensed for severe RSV infection, although systematic reviews find it of no benefit. Passive protection against RSV can be achieved through monthly intramuscular injections of the humanised monoclonal anti-RSV antibody palivizumab (Synagis), and yields a 55% reduction in RSV hospitalisation in susceptible infants. This review assesses immunoglobulin treatment of RSV infection rather than its role as a prophylactic measure. To assess the efficacy of adding human or humanised immunoglobulin therapy to supportive therapy in infants hospitalised with laboratory-determined RSV infection. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2006, issue 1) which contains the Acute Respiratory Infections Group's specialized regsiter, MEDLINE (1966 to Week 4, January 2006) and EMBASE (1980 to September 2005). We also ran searches of reference lists of relevant trials and review articles and searches of personal files. We did not impose any language restrictions. We selected randomised controlled trials (RCTs) that compared immunoglobulin treatment with a placebo control in children hospitalised for RSV infection with bronchiolitis or pneumonia or other lower respiratory tract infection (LRTI) with laboratory-documented RSV infection. The primary outcomes of interest were mortality, length of hospitalisation, length of ventilation and oxygen dependence. Secondary outcome measures were pulmonary function and re-hospitalisations for recurrent breathing difficulties in subsequent years. Any adverse effects of the treatments were also noted, for example, hypersensitivity reactions. Data were extracted but cross-comparison was not possible due to the shortage of studies and

  2. Exon skipping of FcεRIβ eliminates expression of the high-affinity IgE receptor in mast cells with therapeutic potential for allergy

    PubMed Central

    Cruse, Glenn; Yin, Yuzhi; Fukuyama, Tomoki; Desai, Avanti; Arthur, Greer K.; Bäumer, Wolfgang; Beaven, Michael A.; Metcalfe, Dean D.

    2016-01-01

    Allergic diseases are driven by activation of mast cells and release of mediators in response to IgE-directed antigens. However, there are no drugs currently available that can specifically down-regulate mast cell function in vivo when chronically administered. Here, we describe an innovative approach for targeting mast cells in vitro and in vivo using antisense oligonucleotide-mediated exon skipping of the β-subunit of the high-affinity IgE receptor (FcεRIβ) to eliminate surface high-affinity IgE receptor (FcεRI) expression and function, rendering mast cells unresponsive to IgE-mediated activation. As FcεRIβ expression is restricted to mast cells and basophils, this approach would selectively target these cell types. Given the success of exon skipping in clinical trials to treat genetic diseases such as Duchenne muscular dystrophy, we propose that exon skipping of FcεRIβ is a potential approach for mast cell-specific treatment of allergic diseases. PMID:27872312

  3. Role of streams in myxobacteria aggregate formation

    NASA Astrophysics Data System (ADS)

    Kiskowski, Maria A.; Jiang, Yi; Alber, Mark S.

    2004-10-01

    Cell contact, movement and directionality are important factors in biological development (morphogenesis), and myxobacteria are a model system for studying cell-cell interaction and cell organization preceding differentiation. When starved, thousands of myxobacteria cells align, stream and form aggregates which later develop into round, non-motile spores. Canonically, cell aggregation has been attributed to attractive chemotaxis, a long range interaction, but there is growing evidence that myxobacteria organization depends on contact-mediated cell-cell communication. We present a discrete stochastic model based on contact-mediated signaling that suggests an explanation for the initialization of early aggregates, aggregation dynamics and final aggregate distribution. Our model qualitatively reproduces the unique structures of myxobacteria aggregates and detailed stages which occur during myxobacteria aggregation: first, aggregates initialize in random positions and cells join aggregates by random walk; second, cells redistribute by moving within transient streams connecting aggregates. Streams play a critical role in final aggregate size distribution by redistributing cells among fewer, larger aggregates. The mechanism by which streams redistribute cells depends on aggregate sizes and is enhanced by noise. Our model predicts that with increased internal noise, more streams would form and streams would last longer. Simulation results suggest a series of new experiments.

  4. Oligomeric baroeffect and gas aggregation states

    NASA Technical Reports Server (NTRS)

    Noever, David A.

    1992-01-01

    The baroeffect is analyzed to include a gas that aggregates into higher-order polymers or oligomers. The resulting pressure change is found to vary independently of the molecular weight of the gas components and to depend only on the aggregation or oligomeric order of the gas. With increasing aggregation, diffusive slip velocities are found to increase. The calculations are extended to include general counterdiffusion of two distinct aggregation states (k-, j-mer) for the gas, and the pressure change is derived as a function that is independent of both molecular weight and the absolute aggregation. The only parameter that determines the baroeffect is the ratio of aggregated states, beta = k/j. For gases that reversibly aggregate, possible oscillatory behavior and complex dynamics for pressure are discussed. Gas aggregation may play a role for low-temperature crystal-growth conditions in which vapor concentrations of one (or more) species are high.

  5. Virus-induced aggregates in infected cells.

    PubMed

    Moshe, Adi; Gorovits, Rena

    2012-10-17

    During infection, many viruses induce cellular remodeling, resulting in the formation of insoluble aggregates/inclusions, usually containing viral structural proteins. Identification of aggregates has become a useful diagnostic tool for certain viral infections. There is wide variety of viral aggregates, which differ by their location, size, content and putative function. The role of aggregation in the context of a specific virus is often poorly understood, especially in the case of plant viruses. The aggregates are utilized by viruses to house a large complex of proteins of both viral and host origin to promote virus replication, translation, intra- and intercellular transportation. Aggregated structures may protect viral functional complexes from the cellular degradation machinery. Alternatively, the activation of host defense mechanisms may involve sequestration of virus components in aggregates, followed by their neutralization as toxic for the host cell. The diversity of virus-induced aggregates in mammalian and plant cells is the subject of this review.

  6. Evaluation of the transfer of immunoglobulin from colostrum anaerobic fermentation (colostrum silage) to newborn calves.

    PubMed

    Saalfeld, Mara H; Pereira, Daniela I B; Borchardt, Jessica L; Sturbelle, Regis T; Rosa, Matheus C; Guedes, Marcio C; Gularte, Marcia A; Leite, Fábio P Leivas

    2014-11-01

    Colostrum silage is an anaerobic fermentation methodology of excess farm colostrum used to conserve and provide as milk replacement for calves. The present study aimed to evaluate the levels of immunoglobulins present in bovine colostrum silage and its absorption by newborn calves. The concentration of immunoglobulins was determined in fresh colostrum and colostrum silage stored for 12 months. The absorption of immunoglobulins by calves was assessed immediately after birth and 24 h after colostrum silage intake. The immunoglobulin levels were evaluated by ELISA. The results highlighted that colostrum silage kept similar levels of immunoglobulins as the ones in colostrum in natura, and can be transferred to newborn calves with similar amounts to calves fed with colostrum in natura. It is concluded that colostrum silage keeps viable immunoglobulins, and is able to transfer passive immunity to newborn calves.

  7. Protein aggregation in salt solutions

    PubMed Central

    Kastelic, Miha; Kalyuzhnyi, Yurij V.; Hribar-Lee, Barbara; Dill, Ken A.; Vlachy, Vojko

    2015-01-01

    Protein aggregation is broadly important in diseases and in formulations of biological drugs. Here, we develop a theoretical model for reversible protein–protein aggregation in salt solutions. We treat proteins as hard spheres having square-well-energy binding sites, using Wertheim’s thermodynamic perturbation theory. The necessary condition required for such modeling to be realistic is that proteins in solution during the experiment remain in their compact form. Within this limitation our model gives accurate liquid–liquid coexistence curves for lysozyme and γ IIIa-crystallin solutions in respective buffers. It provides good fits to the cloud-point curves of lysozyme in buffer–salt mixtures as a function of the type and concentration of salt. It than predicts full coexistence curves, osmotic compressibilities, and second virial coefficients under such conditions. This treatment may also be relevant to protein crystallization. PMID:25964322

  8. Aggregation resistant zwitterated superparamagnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Rouhana, Layal L.; Schlenoff, Joseph B.

    2012-05-01

    Superparamagnetic nanoparticles (NPs) are promising for biomedical applications since they can be directed toward the organ of interest using an external magnetic field. They are also good contrast agents for magnetic resonance imaging and have potential for the treatment of malignant tumors (i.e., hyperthermia). Therefore, there is a need to produce stable, non-aggregating superparamagnetic nanomaterials that can withstand the in vivo environment. In this work, the colloidal stability of a dispersion of iron oxide NPs was enhanced by functionalizing them with a short zwitterionic siloxane shell in aqueous media. The stabilization procedure yields superparamagnetic nanomaterials, ca. 10 nm in diameter, with saturation magnetization of about 54 emu/g that resist aggregation at physiological salt concentration, temperature, and pH. The loading of the zwitterionic shell was established with diffuse reflectance infrared spectroscopy and thermal gravimetric analysis. X-ray and electron diffraction verified the starting magnetite phase, and that no change in phase occurred on surface functionalization.

  9. Aggregation of Heterogeneously Charged Colloids.

    PubMed

    Dempster, Joshua M; Olvera de la Cruz, Monica

    2016-06-28

    Patchy colloids are attractive as programmable building blocks for metamaterials. Inverse patchy colloids, in which a charged surface is decorated with patches of the opposite charge, are additionally noteworthy as models for heterogeneously charged biological materials such as proteins. We study the phases and aggregation behavior of a single charged patch in an oppositely charged colloid with a single-site model. This single-patch inverse patchy colloid model shows a large number of phases when varying patch size. For large patch sizes we find ferroelectric crystals, while small patch sizes produce cross-linked gels. Intermediate values produce monodisperse clusters and unusual worm structures that preserve finite ratios of area to volume. The polarization observed at large patch sizes is robust under extreme disorder in patch size and shape. We examine phase-temperature dependence and coexistence curves and find that large patch sizes produce polarized liquids, in contrast to mean-field predictions. Finally, we introduce small numbers of unpatched charged colloids. These can either suppress or encourage aggregation depending on their concentration and the size of the patches on the patched colloids. These effects can be exploited to control aggregation and to measure effective patch size.

  10. Mineral resource of the month: aggregates

    USGS Publications Warehouse

    Willett, Jason C.

    2012-01-01

    Crushed stone and construction sand and gravel, the two major types of natural aggregates, are among the most abundant and accessible natural resources on the planet. The earliest civilizations used aggregates for various purposes, mainly construction. Today aggregates provide the basic raw materials for the foundation of modern society.

  11. Locally available aggregate and sediment production

    Treesearch

    Randy B. Foltz; Mark Truebe

    2003-01-01

    Selection of suitable locally available materials to build strong and durable roads with aggregate surfaces is desired to minimize road construction and maintenance costs and to minimize the detrimental effects of sedimentation. Eighteen aggregates were selected from local sources in Idaho, Oregon, South Dakota, and Washington State. Aggregate was placed in shallow...

  12. 24 CFR 58.32 - Project aggregation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 false Project aggregation. 58.32 Section... Environmental Review Process: Documentation, Range of Activities, Project Aggregation and Classification § 58.32 Project aggregation. (a) A responsible entity must group together and evaluate as a single project all...

  13. 24 CFR 58.32 - Project aggregation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Project aggregation. 58.32 Section... Environmental Review Process: Documentation, Range of Activities, Project Aggregation and Classification § 58.32 Project aggregation. (a) A responsible entity must group together and evaluate as a single project all...

  14. 24 CFR 58.32 - Project aggregation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Project aggregation. 58.32 Section... Environmental Review Process: Documentation, Range of Activities, Project Aggregation and Classification § 58.32 Project aggregation. (a) A responsible entity must group together and evaluate as a single project all...

  15. 24 CFR 58.32 - Project aggregation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Project aggregation. 58.32 Section... Environmental Review Process: Documentation, Range of Activities, Project Aggregation and Classification § 58.32 Project aggregation. (a) A responsible entity must group together and evaluate as a single project all...

  16. Improved purification of immunoglobulin G from plasma by mixed-mode chromatography.

    PubMed

    Chai, Dong-Sheng; Sun, Yan; Wang, Xiao-Ning; Shi, Qing-Hong

    2014-12-01

    Efficient loading of immunoglobulin G in mixed-mode chromatography is often a serious bottleneck in the chromatographic purification of immunoglobulin G. In this work, a mixed-mode ligand, 4-(1H-imidazol-1-yl) aniline, was coupled to Sepharose Fast Flow to fabricate AN SepFF adsorbents with ligand densities of 15-64 mmol/L, and the chromatographic performances of these adsorbents were thoroughly investigated to identify a feasible approach to improve immunoglobulin G purification. The results indicate that a critical ligand density exists for immunoglobulin G on the AN SepFF adsorbents. Above the critical ligand density, the adsorbents showed superior selectivity to immunoglobulin G at high salt concentrations, and also exhibited much higher dynamic binding capacities. For immunoglobulin G purification, both the yield and binding capacity increased with adsorbent ligand density along with a decrease in purity. It is difficult to improve the binding capacity, purity, and yield of immunoglobulin G simultaneously in AN SepFF chromatography. By using tandem AN SepFF chromatography, a threefold increase in binding capacity as well as high purity and yield of immunoglobulin G were achieved. Therefore, the tandem chromatography demonstrates that AN SepFF adsorbent is a practical and feasible alternative to MEP HyperCel adsorbents for immunoglobulin G purification. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. 21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... multiple myeloma (tumor of bone marrow cells), Waldenstrom's macroglobulinemia (increased immunoglobulin production by the spleen and bone marrow cells), and lymphoma (tumor of the lymphoid tissues)....

  18. 21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... multiple myeloma (tumor of bone marrow cells), Waldenstrom's macroglobulinemia (increased immunoglobulin production by the spleen and bone marrow cells), and lymphoma (tumor of the lymphoid tissues)....

  19. Managing patients with side effects and adverse events to immunoglobulin therapy.

    PubMed

    Azizi, Gholamreza; Abolhassani, Hassan; Asgardoon, Mohammad Hossein; Shaghaghi, Shiva; Negahdari, Babak; Mohammadi, Javad; Rezaei, Nima; Aghamohammadi, Asghar

    2016-01-01

    Immunoglobulin therapy has not only served as a lifesaving approach for the prevention and treatment of infections in primary and secondary immunodeficiency diseases, but has also been used as an immunomodulatory agent for autoimmune and inflammatory disorders and to provide passive immunity for some infectious diseases. Most of the adverse effects associated with immunoglobulin therapy are mild, transient and self-limiting. However, serious side effects also occur. Therefore, to minimize the adverse events of immunoglobulin therapy, specialist review of patient clinical status and immunoglobulin products, in addition to selection of appropriate treatment strategy for the management of patients with associated side effects and adverse events, are crucial.

  20. Free Immunoglobulin Light Chains as Criteria of Extracorporeal Hemocorrection in Patients with Monoclonal Gammopathies.

    PubMed

    Lyubimova, N V; Timofeeva, Yu S; Gromova, E G; Kuznetsova, L S; Votyakova, O M; Kushlinskii, N E

    2017-08-01

    Elimination of free immunoglobulin light chains with the use of EMic2 selective filters was carried out in 12 patients with monoclonal gammopathies and high production of free immunoglobulin light chains. We showed that extracorporeal detoxification for direct removal of excessive free immunoglobulin light chains from the circulation is advisable for these patients, irrespective of the presence and severity of renal insufficiency. Rapid reduction or elimination of free light chains of immunoglobulins in the course of selective extracorporeal elimination helps to prevent the development of irreversible renal failure and to perform adequate antitumor therapy.

  1. 21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... multiple myeloma (tumor of bone marrow cells), Waldenstrom's macroglobulinemia (increased immunoglobulin production by the spleen and bone marrow cells), and lymphoma (tumor of the lymphoid tissues). (b...

  2. 21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... multiple myeloma (tumor of bone marrow cells), Waldenstrom's macroglobulinemia (increased immunoglobulin production by the spleen and bone marrow cells), and lymphoma (tumor of the lymphoid tissues). (b...

  3. 21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... multiple myeloma (tumor of bone marrow cells), Waldenstrom's macroglobulinemia (increased immunoglobulin production by the spleen and bone marrow cells), and lymphoma (tumor of the lymphoid tissues). (b...

  4. Thrombocytopenia in common variable immunodeficiency patients - clinical course, management, and effect of immunoglobulins.

    PubMed

    Pituch-Noworolska, Anna; Siedlar, Maciej; Kowalczyk, Danuta; Szaflarska, Anna; Błaut-Szlósarczyk, Anita; Zwonarz, Katarzyna

    2015-01-01

    Common variable immunodeficiency (CVID) is a primary immunodeficiency of humoral immunity with heterogeneous clinical features. Diagnosis of CVID is based on hypogammaglobulinaemia, low production of specific antibodies, and disorders of cellular immunity. The standard therapy includes replacement of specific antibodies with human immunoglobulin, prophylaxis, and symptomatic therapy of infections. High prevalence of autoimmunity is characteristic for CVID, most commonly: thrombocytopaenia and neutropaenia, celiac disease, and systemic autoimmune diseases. The study included seven children diagnosed with CVID and treated with immunoglobulin substitution from 2 to 12 years. Thrombocytopenia was diagnosed prior to CVID in four children, developed during immunoglobulin substitution in three children. In one boy with CVID and thrombocytopaenia, haemolytic anaemia occurred, so a diagnosis of Evans syndrome was established. Therapy of thrombocytopaenia previous to CVID included steroids and/or immunoglobulins in high dose, and azathioprine. In children with CVID on regular immunoglobulin substitution, episodes of acute thrombocytopaenia were associated with infections and were treated with high doses of immunoglobulins and steroids. In two patients only chronic thrombocytopaenia was noted. Splenectomy was necessary in one patient because of severe course of thrombocytopaenia. The results of the study indicated a supportive role of regular immunoglobulin substitution in patients with CVID and chronic thrombocytopaenia. However, regular substitution of immunoglobulins in CVID patients did not prevent the occurrence of autoimmune thrombocytopaenia episodes or exacerbations of chronic form. In episodes of acute thrombocytopaenia or exacerbations of chronic thrombocytopaenia, infusions of immunoglobulins in high dose are effective, despite previous regular substitution in the replacing dose.

  5. 21 CFR 866.5510 - Immunoglobulins A, G, M, D, and E immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. (b) Classification. Class...

  6. 21 CFR 866.5510 - Immunoglobulins A, G, M, D, and E immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. (b) Classification. Class...

  7. A randomized multicenter study: safety and efficacy of mini-pool intravenous immunoglobulin versus standard immunoglobulin in children aged 1-18 years with immune thrombocytopenia.

    PubMed

    Elalfy, Mohsen; Reda, Marwa; Elghamry, Islam; Elalfy, Omar; Meabed, Mohamed; El-Ekiaby, Nada; El-Hawy, Mahmoud A; Goubran, Hadi; El-Ekiaby, Magdy

    2017-09-06

    Because there is a global shortage of intravenous immunoglobulin, there is a need for new products to fill the gap. This was a multicenter, open-label study investigating the safety and efficacy of a newly developed mini-pool intravenous immunoglobulin G for children with immune thrombocytopenia. Seventy-two patients ages 1 to 18 years with newly diagnosed (<1 month) immune thrombocytopenia who had platelet counts from 5 to 20 × 10(9) /L with no serious bleeding were recruited from four centers in Egypt. Eligible patients were randomized into three groups 1:1:1. Group A (n = 24) received blood group-specific mini-pool intravenous immunoglobulin in a dose equivalent to immunoglobulin 1 g/kg over 6 to 8 hours, Group B (n = 24) received standard intravenous immunoglobulin (approximately 1g/kg) as a single dose, and Group C (n = 24) did not receive any platelet-enhancing therapy. Parents signed informed consent. Of the patients who received mini-pool intravenous immunoglobulin, 14 achieved a complete response (CR) (58.8%), and four had a response (16.6%). Of the patients who received intravenous immunoglobulin G, 16 achieved a complete response (66.6%), and four had a response (16.6%). In Group C, eight patients achieved a complete response (33.3%), and four had a response (16.6%). The median time to response was 8, 9, and 21 days in Group A, B, and C, respectively, which was significantly higher in Group C than Groups A and B (p < 0.001). Patients in Groups A and B reported 16 adverse drug reactions. Mini-pool intravenous immunoglobulin G was well tolerated, presented no safety issues, and was effective in the treatment of immune thrombocytopenia, with efficacy comparable to that of the standard intravenous immunoglobulin G group, and it was significantly more effective than no treatment. © 2017 AABB.

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

    PubMed

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

    2016-11-01

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

  9. Estimation of major immunoglobulins in smokers and gutkha chewers

    PubMed Central

    Prajapati, Ketankumar Jayantilal; Chawda, Jyoti G

    2016-01-01

    Aim: To estimate the level of IgG and IgA major immunoglobulins in patients having the habit of smoking, gutkha chewing and in patients without any tobacco habit as control. Materials and Methods: Estimation of major immunoglobulins IgG and IgA was carried out by automated Nephelometry method in ten patients (control group), forty patients who had habit of smoking either bidi or cigarette and forty patients who had the habit of gutkha chewing. Among forty patients who smoked, twenty patients were without any lesion while twenty patients had homogenous leukoplakia. Among the forty patients who had habit of gutkha chewing, twenty patients were without any lesion while twenty patients had oral submucous fibrosis (OSMF). The obtained data were analyzed using independent sample t-test. Results: IgG and IgA levels were higher in smokers and gutkha chewers as compared to control group and were higher in gutkha chewers as compared to smokers. IgG and IgA levels of non- lesional smokers and gutkha chewers showed no change as compared to the controls while it was increased in patients with homogenous leukoplakia and patients with OSMF as compared to control group. IgG and IgA levels were also significantly higher in patients with OSMF as compared to that of homogenous leukoplakia. IgG and IgA levels were higher in all the grades of OSMF as compared to the controls and both IgG and IgA levels were directly correlated with the grades of OSMF. Conclusion: Higher major immunoglobulins levels in present study among the study groups indicate the use of immunoprofile estimation in etiology and pathogenesis and would prove a great asset in the proper assessment of the lesions. PMID:27601812

  10. Bovine immunoglobulin protein isolates for the nutritional management of enteropathy.

    PubMed

    Petschow, Bryon W; Blikslager, Anthony T; Weaver, Eric M; Campbell, Joy M; Polo, Javier; Shaw, Audrey L; Burnett, Bruce P; Klein, Gerald L; Rhoads, J Marc

    2014-09-07

    The gastrointestinal tract is responsible for a multitude of digestive and immune functions which depend upon the balanced interaction of the intestinal microbiota, diet, gut barrier function, and mucosal immune response. Disruptions in one or more of these factors can lead to intestinal disorders or enteropathies which are characterized by intestinal inflammation, increased gut permeability, and reduced capacity to absorb nutrients. Enteropathy is frequently associated with human immunodeficiency virus (HIV) infection, inflammatory bowel disease, autoimmune enteropathy, radiation enteritis, and irritable bowel syndrome (IBS), where pathologic changes in the intestinal tract lead to abdominal discomfort, bloating, abnormal bowel function (e.g., diarrhea, urgency, constipation and malabsorption). Unfortunately, effective therapies for the management of enteropathy and restoring intestinal health are still not available. An accumulating body of preclinical studies has demonstrated that oral administration of plasma- or serum-derived protein concentrates containing high levels of immunoglobulins can improve weight, normalize gut barrier function, and reduce the severity of enteropathy in animal models. Recent studies in humans, using serum-derived bovine immunoglobulin/protein isolate, demonstrate that such protein preparations are safe and improve symptoms, nutritional status, and various biomarkers associated with enteropathy. Benefits have been shown in patients with HIV infection or diarrhea-predominant IBS. This review summarizes preclinical and clinical studies with plasma/serum protein concentrates and describes the effects on host nutrition, intestinal function, and markers of intestinal inflammation. It supports the concept that immunoglobulin-containing protein preparations may offer a new strategy for restoring functional homeostasis in the intestinal tract of patients with enteropathy.

  11. Facilitated subcutaneous immunoglobulin (fSCIg) therapy--practical considerations.

    PubMed

    Ponsford, M; Carne, E; Kingdon, C; Joyce, C; Price, C; Williams, C; El-Shanawany, T; Williams, P; Jolles, S

    2015-12-01

    There is an increasing range of therapeutic options for primary antibody-deficient patients who require replacement immunoglobulin. These include intravenous immunoglobulin (IVIg), subcutaneous immunoglobulin (SCIg), rapid push SCIg and most recently recombinant human hyaluronidase-facilitated SCIg (fSCIg). Advantages of fSCIg include fewer needle punctures, longer infusion intervals and an improved adverse effect profile relative to IVIg. Limited real-life experience exists concerning the practical aspects of switching or starting patients on fSCIg. We describe the first 14 patients who have been treated with fSCIg at the Immunodeficiency Centre for Wales (ICW), representing more than 6 patient-years of experience. The regimen was well tolerated, with high levels of satisfaction and no increase in training requirement, including for a treatment-naive patient. Two patients discontinued fSCIg due to pain and swelling at the infusion site, and one paused therapy following post-infusion migraines. Ultrasound imaging of paired conventional and facilitated SCIg demonstrated clear differences in subcutaneous space distribution associated with a 10-fold increase in rate and volume delivery with fSCIg. Patient profiles for those choosing fSCIg fell into two main categories: those experiencing clinical problems with their current treatment and those seeking greater convenience and flexibility. When introducing fSCIg, consideration of the type and programming of infusion pump, needle gauge and length, infusion site, up-dosing schedule, home training and patient information are important, as these may differ from conventional SCIg. This paper provides guidance on practical aspects of the administration, training and outcomes to help inform decision-making for this new treatment modality.

  12. Immunomodulatory activity accompanying chicken egg yolk immunoglobulin Y.

    PubMed

    Polanowski, A; Zabłocka, A; Sosnowska, A; Janusz, M; Trziszka, T

    2012-12-01

    Immunity transfer from a mother to the newborn does not depend exclusively on immunoglobulins. Peptides, which are characterized by immunoregulatory properties that accompany IgG(2), known as proline-rich polypeptide complex (PRP), have been discovered for the first time in ovine colostrum. In this report we present new data showing that some immunoregulatory peptides associated with the main immunoglobulin class, IgY, are also present in the avian immune system. Cytokine-inducing activity of particular fractions obtained from ovine colostrum, IgG+ (IgG(2) containing PRP), IgG- (IgG(2) free of PRP), and purified PRP, was compared with that of crude egg yolk IgY (IgY+), additionally purified egg yolk IgY (IgY-), and polypeptides accompanying IgY named Yolkin (Y), using an ex vivo model of whole human blood cells. It was shown that both IgG+ fraction and PRP, but not IgG-, stimulated the whole blood cells to release tumor necrosis factor-α and interleukin-1β cytokines. Similar experiments performed with hen's egg IgY preparations showed that IgY+ and Y samples showed higher cytokine-inducing activity than samples additionally purified with the use of size exclusion chromatography (IgY-). The IgY+ at a dose of 100 μg was even more active than the positive lipopolysaccharide control. It was also found that Y is able to stimulate macrophage cell line J774.2 to release nitric oxide. The results obtained suggest that IgY, the main chicken immunoglobulin fraction, is accompanied by additional polypeptides and plays a role of a transporter of biologically active substances, which was observed in the case of colostral IgG.

  13. Intravenous immunoglobulin transfusion in colostrum-deprived dairy calves.

    PubMed

    Boccardo, A; Belloli, A; Biffani, S; Locatelli, V; Dall'Ara, P; Filipe, J; Restelli, I; Proverbio, D; Pravettoni, D

    2016-03-01

    Immunoglobulin transfusion is employed in the management of the failure of passive transfer (FPT). The aim of this study was to investigate the dose of immunoglobulin G (IgG) needed to reach a protective concentration (>10 g/L) in colostrum-deprived dairy calves. Twenty-eight Holstein Friesian newborn male calves were randomly assigned to either a control group (CG) or a treatment group (PG). Calves in the CG received 4 L of high quality colostrum within 12 h of birth. Calves in the PG received 62.7 ± 3.1 g of IgG IV in 2.6 ± 0.3 L of plasma within 6 h after birth. Serum immunoglobulin G (sIgG) and serum total protein (sTP) concentrations were assayed before and after (24 h, 72 h and 1 week after birth) plasma transfusion or colostrum ingestion. Serum (s) IgG and sTP concentrations increased in both groups throughout the period of observation. Mean sIgG and sTP concentrations after colostrum ingestion or plasma transfusion were higher in the CG than in the PG (P <0.01). Nine treated calves developed diarrhoea during the study and four were humanely euthanased due to progressive clinical deterioration. None of the calves in the CG showed signs of disease or died during the study. The dose of IgG used in this trial effectively provided an adequate sIgG concentration in colostrum-deprived calves (>10 g/L). Calves in the CG had significantly lower morbidity and mortality rates compared to those in the PG, suggesting that plasma transfusion alone is ineffective in providing complete protection against neonatal disease.

  14. Beneficiation of natural aggregates by polymer impregnation

    SciTech Connect

    Webster, R.P.; Fontana, J.J.

    1980-09-01

    The use of polymer impregnation as a means of upgrading natural aggregates has been investigated. The effect of polymer impregnation on the physical and mechanical properties was evaluated in a series of tests performed using four aggregates of varying quality. The strength of concrete cast with polymer impregnated coarse aggregate was also tested. Two monomer systems were used in the investigation; a methyl methacrylate-based system and a styrene-based system. In general, significant improvements in the physical and mechanical properties of each of the four aggregates resulted from polymer impregnation. The strength of concrete cast with impregnated aggregates varied, being increased in some cases and decreased in others.

  15. [Lysophosphatidic acid and human erythrocyte aggregation].

    PubMed

    Sheremet'ev, Iu A; Popovicheva, A N; Levin, G Ia

    2014-01-01

    The effects of lysophosphatidic acid on the morphology and aggregation of human erythrocytes has been studied. Morphology of erythrocytes and their aggregates were studied by light microscopy. It has been shown that lysophosphatidic acid changes the shape of red blood cells: diskocyte become echinocytes. Aggregation of red blood cells (rouleaux) was significantly reduced in autoplasma. At the same time there is a strong aggregation of echinocytes. This was accompanied by the formation of microvesicles. Adding normal plasma to echinocytes restores shape and aggregation of red blood cells consisting of "rouleaux". A possible mechanism of action of lysophosphatidic acid on erythrocytes is discussed.

  16. [AGGREGATION OF METABOLICALLY DEPLETED HUMAN ERYTHROCYTES].

    PubMed

    Sheremet'ev, Yu A; Popovicheva, A N; Rogozin, M M; Levin, G Ya

    2016-01-01

    An aggregation of erythrocytes in autologous plasma after blood storage for 14 days at 4 °C was studied using photometry and light microscopy. The decrease of ATP content, the formation of echinocytes and spheroechinocytes, the decrease of rouleaux form of erythrocyte aggregation were observed during the storage. On the other hand the aggregates of echinocytes were formed in the stored blood. The addition of plasma from the fresh blood didn't restore the normal discocytic shape and aggregation of erythrocytes in the stored blood. The possible mechanisms of erythrocytes and echinocytes aggregation are discussed.

  17. A Case of Immunoglobulin E Mediated Anaphylaxis to Levodropropizine

    PubMed Central

    Park, Kyung Hee; Yun, Il Seon; Choi, Soo-Young; Lee, Jae-Hyun; Hong, Chein-Soo

    2013-01-01

    We experienced a case of immunoglobulin E (IgE) mediated anaphylaxis to levodropropizine. The patient was an 18-year old Korean woman. After taking the common cold medication including acetaminophen, domperidone, and levodropropizine, skin rash, angioedema and anaphylaxis were developed immediately. As she was tolerable to acetaminophen alone, we thought the culprit agent was maybe a levodropropizine tablet. To confirm the culprit, she underwent skin prick test and oral drug provocation test with the suspected one. Finally we detected levodropropizine specific IgE and confirmed the specificity by inhibition enzyme-linked immunosorbent assay (ELISA). PMID:23225830

  18. Production and characterization of monoclonal antibodies against dog immunoglobulin isotypes.

    PubMed

    Arce, C; Moreno, A; Millán, Y; Martín de las Mulas, J; Llanes, D

    2002-09-06

    A panel of six monoclonal antibodies (mAbs) recognizing antigenic determinants on canine immunoglobulin (Ig) heavy or light chains was produced and characterized. All monoclonals recognized the IgG(2) subclass, although only two were subclass-specific (CA3H1 and CA4F1). The CA3B8 mAb was found to be specific for an epitope on canine immunoglobulin G heavy chain, (IgG(1) and IgG(2) subclasses). Two mAbs (CA2E9 and CA5B2) reacted with an epitope on the heavy chain of canine IgG and IgM and another, CA4E7, bound to canine IgA, IgG and IgM isotypes; CA4E7 recognized an epitope on canine immunoglobulin light chain. CA4E7, CA4F1 and CA5B2 recognized an epitope in the Fab region. Three mAbs, CA3B8, CA4E7 and CA5B2, showed much lower reactivity with canine IgG by ELISA when IgG was periodate-treated, suggesting that they recognized a carbohydrate determinant. Cross-reactivity analysis of these mAbs with sera from horse, goat, cow, sheep, pig, cat, rabbit, hamster, rat, mouse and human indicated that two mAbs, CA3B8 and CA5B2, recognized a canine IgG-specific epitope; two others, CA3H1 and CA4E7, recognized an epitope also present in rabbit and sheep immunoglobulin respectively; and the remaining two (CA2E9 and CA4F1) recognized an epitope broadly present on the Igs of the species analyzed. This panel of antibodies will be a useful tool for future canine immunodiagnosis tests. With the exception of CA2E9, all mAbs were able to recognize plasma cells on paraffin-embedded tissues, and will thus be useful for immunohistochemical assays.

  19. Immunoglobulin Concentration in Tears of Contact Lens Wearers

    PubMed Central

    Maurya, Rajendra P.; Bhushan, Prashant; Singh, Virendra P.; Singh, Mahendra K.; Kumar, Prakash; Bhatia, Ravindra P.S.; Singh, Usha

    2014-01-01

    Purpose: To evaluate changes in the concentration of tear immunoglobulins in contact lens wearers. Methods: A total of 45 cases including 23 contact lens wearers (43 eyes) and 22 age and sex matched healthy controls having no ocular pathology were studied for immunoglobulins (IgA, IgG, IgM) in their tears by single radial immunodiffusion method. Results: Most of the cases used soft (56.6%) and semi-soft gas permeable (30.4%) contact lenses. Tear IgM was detected in only 17.4% and tear IgG in 43.6% of contact lens wearers, while in controls IgG was detected in 9.1% but none of the controls had IgM. There was a significant rise in total tear IgA (13.17 ± 4.44 mg/dl) in contact lens wearer as compared to controls (8.93 ± 3.79 mg/dl). Rise of tear IgA was more in symptomatic patients (15.38 ± 5.28 mg/dl) and in those wearing hard (19.73 ± 5.43 mg/dl) and semi-soft contact lenses (13.31 ± 5.43 mg/dl). A significant increase in tear IgA was noticed in subjects wearing lenses for >3 years (15.69 ± 5.39 mg/dl). About 43.4% of lens wearers were symptomatic and 80% of their lenses showed deposits and/or haziness. All cases with IgM in tear were symptomatic. Conclusion: The relation of immunoglobulin concentration with increasing duration of wear and material of contact lens shows that tear immunoglobulin rise accrues due to mechanical stimulation, hence contact lenses should not be used for a long period and lenses of hard nature should be discouraged. The maintenance, cleaning and deproteinization of the lenses are of high importance to avoid immunostimulation. PMID:25667732

  20. Serum immunoglobulins in newborn calves before and after colostrum feeding.

    PubMed

    Merriman, M J

    1971-10-01

    Pre-colostral and post-colostral sera of seven Holstein calves and colostral whey were analyzed immunoelectrophoretically. IgM, IgG(1) (fast), and IgG(2) (slow) were demonstrated while IgA was not detected in serum of new-born calves before colostrum feeding. In post-colostral serum IgG, IgM, in relatively higher levels, and IgA were present which corresponded with the classes of immunoglobulins found in whey. These observations suggest that the developing bovine fetus may be capable of independent immune response.

  1. Alterations in immunoglobulin & complement levels in chronic obstructive pulmonary disease.

    PubMed

    Chauhan, S; Gupta, M K; Goyal, A; Dasgupta, D J

    1990-08-01

    Thirty patients of chronic obstructive pulmonary disease (COPD; all smokers) and an equal number of controls (15 smokers) were studied. The COPD patients were further divided into group A (predominantly emphysema) and group B (predominantly bronchitis) of 15 patients each. Serum and sputum IgG, IgA and IgM and serum C3 and C4 were estimated. IgG, IgA, IgM and C3 and C4 were similar in smoker and non-smoker controls. Mean (+/- SD) serum IgG (IU/ml) was significantly higher in COPD patients (207.78 +/- 62.73) than in control (177.25 +/- 43.5; P less than 0.05), serum IgA (IU/ml) was also significantly higher in COPD (205.04 +/- 46.56) than in control (108.21 +/- 33.3; P less than 0.01). IgM was similar in the 2 groups. Sputum IgA (IU/ml) was higher in COPD (4.68 +/- 3.51) than in control (2.25 +/- 1.03; P less than 0.05). IgG and IgM were similar in the 2 groups. Both serum C3 (IU) and C4 (IU) were lower in COPD patients (C3 = 95.9 +/- 33.11, C4 = 113.6 +/- 62.4) than in control (C3 = 167.3 +/- 25.42, C4 = 205 +/- 76.5; P less than 0.05). Serum IgA in type B COPD (212.25 +/- 50.06) was higher than in type A (197.52 +/- 43.3; P less than 0.05) IgG and IgM were similar in these 2 groups. In COPD patients, immunoglobulins were either normal or higher indicating that deficiency of immunoglobulin is not a predisposing factor in development of COPD. Similar immunoglobulin values in smoker and nonsmoker controls indicated that smoking was not the cause of rise of immunoglobulins in COPD.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Tuberculosis in a case of hyper immunoglobulin E syndrome

    PubMed Central

    Ashtekar, Renuka; Shah, Ira

    2016-01-01

    Hyper immunoglobulin E syndrome (HIES) is a rare primary immunodeficiency disorder characterized by elevated serum IgE, dermatitis, and immunodeficiency that predisposes to multiple skin and lung infections. The most frequent pathogen responsible for infections in these patients is Staphylococcus aureus. Tuberculosis (TB) in patients with HIES is an uncommon finding, and there are only a few reports of mycobacterial infections in known cases of HIES. We present a case of abdominal TB that developed in a 15-year-old boy who also had HIES.

  3. Clonal immunoglobulin gene rearrangement in the infarcted lymph node syndrome.

    PubMed

    Laszewski, M J; Belding, P J; Feddersen, R M; Lutz, C T; Goeken, J A; Kemp, J D; Dick, F R

    1991-07-01

    The authors report a case of complete lymph node infarction in which a specific etiology could not be determined by morphologic or immunophenotypic studies; however, clonal rearrangement of the immunoglobulin gene was demonstrated by Southern blot hybridization of DNA extracted from the necrotic tissue. A subsequent lymph node biopsy later was diagnosed as malignant lymphoma, using morphologic, immunophenotypic and genotypic criteria. Identical clonally rearranged bands were present in DNA from both the infarcted nodal and the subsequent tissue biopsies. In the setting of lymph node necrosis, gene rearrangement studies may provide diagnostic information concerning clonality, even if morphologic and immunophenotypic studies are indeterminate for a lymphoproliferative process.

  4. [Exfoliative dermatitis as a side effect of intravenous immunoglobulin treatment].

    PubMed

    Markvardsen, Lars Høj; Jakobsen, Johannes

    2011-10-24

    Three patients with immune-mediated polyneuropathies developed rash, eczema, whole body scaling, vesicles in hands and loss of hair a few days after infusion of large doses of intravenous immunoglobulin (IVIG). The condition was diagnosed as exfoliative dermatitis. Two out of three patients were afterwards treated with low doses of IVIG slowly increased over a year given under the protection of oral steroids. Our findings indicate that exfoliative dermatitis can be provoked by IVIG treatment, and that the treatment can be reinstalled by slowly increasing the IVIG dose under steroid cover.

  5. Erythrocyte aggregation: basic aspects and clinical importance.

    PubMed

    Baskurt, Oguz K; Meiselman, Herbert J

    2013-01-01

    Red blood cell (RBC) aggregate to form two- and three-dimensional structures when suspended in aqueous solutions containing large plasma proteins or polymers; this aggregation is reversible and shear dependent (i.e., dispersed at high shear and reformed at low or stasis). The extent of aggregation is the main determinant of low shear blood viscosity, thus predicting an inverse relationship between aggregation and in vivo blood flow. However, the effects of aggregation on hemodynamic mechanisms (e.g., plasma skimming, Fåhraeus Effect, microvascular hematocrit) may promote rather than impede vascular blood flow. The impact of enhanced RBC aggregation on endothelial function and hemostatic mechanisms adds further complexity, thereby requiring specific attention to the nature, extent and time course of aggregation when considering its overall influence on tissue perfusion. A detailed understanding of aggregation effects is important from a clinical point of view since it may be enhanced during a variety of pathophysiological processes, including infections, circulatory and metabolic disorders, hematological pathologies and several other disease states. Altered RBC aggregation may be an indicator of disease as well as a factor affecting the course of the clinical condition; the prognostic value of RBC aggregation indices has been demonstrated in various diseases. Currently, RBC aggregation is an easily and accurately measurable parameter, and therefore may be expected to have broader clinical usage in the future.

  6. Simulation of J-aggregate microcavity photoluminescence

    NASA Astrophysics Data System (ADS)

    Michetti, Paolo; La Rocca, Giuseppe C.

    2008-05-01

    We have developed a model in order to account for the photoexcitation dynamics of J-aggregate films and strongly coupled J-aggregate microcavities. The J aggregates are described as a disordered Frenkel exciton system in which relaxation occurs due to the presence of a thermal bath of molecular vibrations. The correspondence between the photophysics in J-aggregate films and that in J-aggregate microcavities is obtained by introducing a model polariton wave function mixing cavity photon modes and J-aggregate super-radiant excitons. With the same description of the material properties, we have calculated both absorption and luminescence spectra for the J-aggregate film and the photoluminescence of strongly coupled organic microcavities. The model is able to account for the fast relaxation dynamics in organic microcavities following nonresonant pumping and explains the temperature dependence of the ratio between the upper polariton and the lower polariton luminescence.

  7. Heating of Porous Icy Dust Aggregates

    NASA Astrophysics Data System (ADS)

    Sirono, Sin-iti

    2017-06-01

    At the beginning of planetary formation, highly porous dust aggregates are formed through coagulation of dust grains. Outside the snowline, the main component of an aggregate is H2O ice. Because H2O ice is formed in amorphous form, its thermal conductivity is extremely small. Therefore, the thermal conductivity of an icy dust aggregate is low. There is a possibility of heating inside an aggregate owing to the decay of radionuclides. It is shown that the temperature increases substantially inside an aggregate, leading to crystallization of amorphous ice. During the crystallization, the temperature further increases sufficiently to continue sintering. The mechanical properties of icy dust aggregates change, and the collisional evolution of dust aggregates is affected by the sintering.

  8. Microwave extinction characteristics of nanoparticle aggregates

    NASA Astrophysics Data System (ADS)

    Wu, Y. P.; Cheng, J. X.; Liu, X. X.; Wang, H. X.; Zhao, F. T.; Wen, W. W.

    2016-07-01

    Structure of nanoparticle aggregates plays an important role in microwave extinction capacity. The diffusion-limited aggregation model (DLA) for fractal growth is utilized to explore the possible structures of nanoparticle aggregates by computer simulation. Based on the discrete dipole approximation (DDA) method, the microwave extinction performance by different nano-carborundum aggregates is numerically analyzed. The effects of the particle quantity, original diameter, fractal structure, as well as orientation on microwave extinction are investigated, and also the extinction characteristics of aggregates are compared with the spherical nanoparticle in the same volume. Numerical results give out that proper aggregation of nanoparticle is beneficial to microwave extinction capacity, and the microwave extinction cross section by aggregated granules is better than that of the spherical solid one in the same volume.

  9. Protein aggregation: From background to inhibition strategies.

    PubMed

    Alam, Parvez; Siddiqi, Khursheed; Chturvedi, Sumit Kumar; Khan, Rizwan Hasan

    2017-10-01

    The aggregation of specific proteins is hypothesized to cause several pathological conditions, which are collectively known as amyloid disorders. The aggregation of peptides and proteins is mainly associated with the perturbation of cellular function, ageing and various human disorders. Mounting evidence suggests that protein aggregation is often caused by mutation, environmental stress or the cellular response to an imbalanced protein homeostasis. This review summarizes the background information on the protein folding, misfolding, cellular strategies against protein aggregation, factors affecting protein aggregation and mechanism of protein aggregation. We then focus on various inhibitors for protein aggregation both in vitro and in vivo. We conclude with a perspective that better therapeutics could be developed by using cocktail of small molecule inhibitors for the treatment of amyloid diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Aggregation Kinetics of Interrupted Polyglutamine Peptides

    PubMed Central

    Walters, Robert H.; Murphy, Regina M.

    2011-01-01

    Abnormally expanded polyglutamine domains are associated with at least nine neurodegenerative diseases, including Huntington’s disease. Expansion of the glutamine region facilitates aggregation of the impacted protein, and aggregation has been linked to neurotoxicity. Studies of synthetic peptides have contributed substantially to our understanding of the mechanism of aggregation, because the underlying biophysics of polyglutamine-mediated association can be probed independent of their context within a larger protein. In this report, interrupting residues were inserted into polyglutamine peptides (Q20), and the impact on conformational and aggregation properties was examined. A peptide with 2 alanine residues formed laterally-aligned fibrillar aggregates which were similar to the uninterrupted Q20 peptide. Insertion of 2 proline residues resulted in soluble, nonfibrillar aggregates, which did not mature into insoluble aggregates. In contrast, insertion of a β-turn template DPG rapidly accelerated aggregation and resulted in a fibrillar aggregate morphology with little lateral alignment between fibrils. These results are interpreted to indicate that (a) long-range nonspecific interactions lead to the formation of soluble oligomers, while maturation of oligomers into fibrils requires conformational conversion, and (b) that soluble oligomers dynamically interact with each other, while insoluble aggregates are relatively inert. Kinetic analysis revealed that the increase in aggregation caused by the DPG insert is inconsistent with the nucleation-elongation mechanism of aggregation featuring a monomeric β-sheet nucleus. Rather, the data support a mechanism of polyglutamine aggregation by which monomers associate into soluble oligomers, which then undergo slow structural rearrangement to form sedimentable aggregates. PMID:21821045

  11. Differential protein analysis of serum exosomes post-intravenous immunoglobulin therapy in patients with Kawasaki disease.

    PubMed

    Zhang, Li; Song, Qi-Fang; Jin, Jing-Jie; Huang, Ping; Wang, Zhou-Ping; Xie, Xiao-Fei; Gu, Xiao-Qiong; Gao, Xue-Juan; Jia, Hong-Ling

    2017-08-14

    Kawasaki disease, which is characterised by systemic vasculitides accompanied by acute fever, is regularly treated by intravenous immunoglobulin to avoid lesion formation in the coronary artery; however, the mechanism of intravenous immunoglobulin therapy is unclear. Hence, we aimed to analyse the global expression profile of serum exosomal proteins before and after administering intravenous immunoglobulin. Two-dimensional electrophoresis coupled with mass spectrometry analysis was used to identify the differentially expressed proteome of serum exosomes in patients with Kawasaki disease before and after intravenous immunoglobulin therapy. Our analysis revealed 69 differential protein spots in the Kawasaki disease group with changes larger than 1.5-fold and 59 differential ones in patients after intravenous immunoglobulin therapy compared with the control group. Gene ontology analysis revealed that the acute-phase response disappeared, the functions of the complement system and innate immune response were enhanced, and the antibacterial humoral response pathway of corticosteroids and cardioprotection emerged after administration of intravenous immunoglobulin. Further, we showed that complement C3 and apolipoprotein A-IV levels increased before and decreased after intravenous immunoglobulin therapy and that the insulin-like growth factor-binding protein complex acid labile subunit displayed reverse alteration before and after intravenous immunoglobulin therapy. These observations might be potential indicators of intravenous immunoglobulin function. Our results show the differential proteomic profile of serum exosomes of patients with Kawasaki disease before and after intravenous immunoglobulin therapy, such as complement C3, apolipoprotein A-IV, and insulin-like growth factor-binding protein complex acid labile subunit. These results may be useful in the identification of markers for monitoring intravenous immunoglobulin therapy in patients with Kawasaki disease.

  12. The effect of immunoglobulins and somatic cells on the gravity separation of fat, bacteria, and spores in pasteurized whole milk.

    PubMed

    Geer, S R; Barbano, D M

    2014-01-01

    Our objective was to determine the role that immunoglobulins and somatic cells (SC) play in the gravity separation of milk. The experiment comprised 9 treatments: (1) low-temperature pasteurized (LTP; 72°C for 17.31s) whole milk; (2) LTP (72°C for 17.31s) whole milk with added bacteria and spores; (3) recombined LTP (72°C for 17.31s) whole milk with added bacteria and spores; (4) high-temperature pasteurized (HTP; 76°C for 7min) whole milk with added bacteria and spores; (5) HTP (76°C for 7min) whole milk with added bacteria and spores and added colostrum; (6) HTP (76°C for 7min) centrifugally separated, gravity-separated (CS GS) skim milk with HTP (76°C for 7min) low-SC cream with added bacteria and spores; (7) HTP (76°C for 7min) CS GS skim milk with HTP (76°C for 7min) high-SC cream with added bacteria and spores; (8) HTP (76°C for 7min) CS GS skim milk with HTP (76°C for 7min) low-SC cream with added bacteria and spores and added colostrum; and (9) HTP (76°C for 7min) CS GS skim milk with HTP (76°C for 7min) high-SC cream with added bacteria and spores and added colostrum. The milks in the 9 treatments were gravity separated at 4°C for 23h in glass columns. Five fractions were collected by weight from each of the column treatments, starting from the bottom of the glass column: 0 to 5%, 5 to 90%, 90 to 96%, 96 to 98%, and 98 to 100%. The SC, fat, bacteria, and spores were measured in each of the fractions. The experiment was replicated 3 times in different weeks using a different batch of milk and different colostrum. Portions of the same batch of the frozen bacteria and spore solutions were used for all 3 replicates. The presence of both SC and immunoglobulins were necessary for normal gravity separation (i.e., rising to the top) of fat, bacteria, and spores in whole milk. The presence of immunoglobulins alone without SC was not sufficient to cause bacteria, fat, and spores to rise to the top. The interaction between SC and immunoglobulins was

  13. Streptococcus pneumoniae antibody titres in patients with primary antibody deficiency receiving intravenous immunoglobulin (IVIG) compared to subcutaneous immunoglobulin (SCIG).

    PubMed

    Knutsen, A P; Leiva, L E; Caruthers, C; Rodrigues, J; Sorensen, R U

    2015-10-01

    Intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin (SCIG) are effective in the treatment of patients with primary antibody deficiency disorders (PAD). The purpose of this study was to evaluate Streptococcus pneumoniae (Spn) antibody titres to 14 serotypes in patients receiving IVIG compared to SCIG and to correlate Spn antibody levels to clinical outcome. The doses of immunoglobulin (Ig)G/kg/month were similar in both IVIG and SCIG groups. In 11 patients treated with IVIG, Spn antibody titres were ≥ 1·3 μg/ml to 99·4 ± 2·1% of the 14 serotypes at peak IVIG but decreased to 66·9 ± 19·8% at trough IVIG. Loss of Spn titres ≥ 1·3 μg/ml was most frequent for Spn serotypes 1, 4, 9V and 23. This correlated with lower Spn antibody titres to these serotypes at peak IVIG compared to the other serotypes. In 13 patients treated with SCIG, Spn antibody titres were protective to 58·2 ± 23·3% of the serotypes 3-5 days after infusion, similar to trough IVIG. Similarly, the Spn serotypes with the least protective percentages were the same as the ones observed in trough IVIG. There were no annualized serious bacterial infections (aSBI) in either group. However, there were significantly decreased annualized other infections (aOI) in the SCIG group compared to the IVIG-treated group, 0·8 ± 0·7 versus 2·2 ± 1·2 infections/patient/year (P = 0·004). Breakthrough aOI did not correlate with protective or higher serum Spn antibody titres. © 2015 British Society for Immunology.

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

    PubMed

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

    2005-01-01

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

  15. Effect of a Modified Kaolin Treatment on Serum Immunoglobulins

    PubMed Central

    Inouye, Sakae; Kono, Reisaku

    1972-01-01

    After kaolin treatment of fetal rabbit serum, 7S antibody titers were reduced more than 19S titers. This reduction was less when the kaolin treatment was performed at pH 9.0 than when it was performed at pH 7.3. A modification of the kaolin treatment of sera for use in the hemagglutination-inhibiting antibody titration, in which the hemagglutination reaction is performed at a neutral pH, is recommended. The advantage of the modified method is that adsorption of immunoglobulins to kaolin is minimized when serum is treated at a lower dilution with pH 9.0 kaolin, followed by reduction of the pH of the supernatant fluid to neutrality with a „serum adjusting diluent.” When the serum was diluted with physiological saline before kaolin treatment, a great decrease in serum immunoglobulin concentrations occurred. This decrease was found to be less in the modified kaolin treatment than in the conventional pH 7.3 kaolin treatment. PMID:4622816

  16. Serum immunoglobulin levels in healthy children and adults

    PubMed Central

    Stoop, J. W.; Zegers, B. J. M.; Sander, P. C.; Ballieux, R. E.

    1969-01-01

    Serum levels of IgM, IgG and IgA were determined in 270 healthy children, 4–12 years old, and in thirty healthy adults by the radial immunodiffusion method of Mancini. There were nine 1-year age groups of thirty children each (fifteen boys and fifteen girls); the adult group consisted of fifteen males and fifteen females. The difference in values between adults and children was statistically significant. The IgG and IgA concentrations showed a gradual rise with increasing age; the IgM concentration remained constant at a distinctly lower level than that in adults. The IgA level was about the same in both sexes. Girls had significantly higher IgM and IgG levels than boys. A consistent seasonal influence on the three serum immunoglobulin concentrations could not be demonstrated. A very wide variation in serum levels of each immunoglobulin in each age group was found. Very low values were by no means exceptional. The consequence of this finding for the diagnosis of immunological incompetency is discussed. PMID:4182354

  17. Naturally occurring antibodies/autoantibodies in polyclonal immunoglobulin concentrates.

    PubMed

    Späth, Peter J; Lutz, Hans U

    2012-01-01

    It was a long way from the use of hyperimmune animal sera for the treatment of toxin-producing infections to the production of polyclonal, polyspecific human immunoglobulin preparations and the use of NAbs as therapeutic tools for autoimmune and inflammatory diseases. Some highlights of the development of knowledge in blood fractionation techniques, basic science and clinical wisdom are reviewed in this chapter. Proudly we mention the outstanding contribution of Swiss scientists and clinicians in the development of IVIG as clinical tool for some otherwise untreatable diseases or taking advantage of its low adverse event profile in long-term treatment of other chronic autoimmune and inflammatory diseases. This chapter summarizes some of the characteristics and the effects in humans of NAbs which are present in IgG concentrates. We call attention to the fact that the human data remain, at least in part, incomplete, among others because even with the most efficient large-scale techniques available not more than approximately 50% of the total IgG in plasma can be fractionated into an immunoglobulin G concentrate.

  18. Structural and functional mapping of immunoglobulin V-regions.

    PubMed

    Fougereau, M; Schiff, C; Mathieu, C; de Préval, C; Bourgois, A; Moulin, A; Rocca-Serra, J

    1976-01-01

    V-regions of immunoglobulins chains contain 3 types of positions, which are equally represented: invariant and sub-group characteristic, which account for the "framework" and hypervariable positions, responsible for antigen recognition. The 3 types of positions are grouped and fall within a very few discrete stretches. Sub-group characteristic segments containing one of the 2 cysteyl residues of the V-regions may be isolated by high voltage paper electrophoresis and provide a basis to type for sub-groups in the VK and in the VH human systems. This allowed to characterize a large set of human myeloma proteins that were used in a series of competitive hybridizations which indicated that sub-groups had no influence on preferential reassociations, which occurred in 80% of the cases. This preference seems to rely mostly on individual structural differences, which may be linked to heterogeneity at the framework level. Distinction between framework heterogeneity and hypervariable regions heterogeneity may be approached by raising antibodies against a mouse myeloma protein, MOPC 173, of known sequence, by means of syngeneic and allogeneic immunizations, using Balb/c and A/J mice. Junction of distinct portions of immunoglobulin chains such as the V and the C regions raises the possibility that some recognition signals may operate at the DNA level. Since rotational symmetry regions in the DNA are known to act as such signals, it is discussed whether such regions can be expected from the amino acid sequence data, especially in the vicinity of the "switch" peptide.

  19. Serum Immunoglobulin A Cross-Strain Blockade of Human Noroviruses

    PubMed Central

    Lindesmith, Lisa C.; Beltramello, Martina; Swanstrom, Jesica; Jones, Taylor A.; Corti, Davide; Lanzavecchia, Antonio; Baric, Ralph S.

    2015-01-01

    Background. Human noroviruses are the leading cause of acute viral gastroenteritis, justifying vaccine development despite a limited understanding of strain immunity. After genogroup I (GI).1 norovirus infection and immunization, blockade antibody titers to multiple virus-like particles (VLPs) increase, suggesting that GI cross-protection may occur. Methods. Immunoglobulin (Ig)A was purified from sera collected from GI.1-infected participants, and potential neutralization activity was measured using a surrogate neutralization assay based on antibody blockade of ligand binding. Human and mouse monoclonal antibodies (mAbs) were produced to multiple GI VLPs to characterize GI epitopes. Results. Immunoglobulin A purified from day 14 post-GI.1 challenge sera blocked binding of GI.1, GI.3, and GI.4 to carbohydrate ligands. In some subjects, purified IgA preferentially blocked binding of other GI VLPs compared with GI.1, supporting observations that the immune response to GI.1 infection may be influenced by pre-exposure history. For other subjects, IgA equivalently blocked multiple GI VLPs. Only strain-specific mAbs recognized blockade epitopes, whereas strain cross-reactive mAbs recognized nonblockade epitopes. Conclusions. These studies are the first to describe a functional role for serum IgA in norovirus immunity and the first to characterize human monoclonal antibodies to GI strains, expanding our understanding of norovirus immunobiology. PMID:26180833

  20. Salivary and serum immunoglobulin levels in cats with chronic gingivostomatitis.

    PubMed

    Harley, R; Gruffydd-Jones, T J; Day, M J

    2003-02-01

    The salivary and serum concentrations of immunoglobulins G, M and A (IgG, IgM and IgA), and the salivary concentrations of albumin were measured by ELISA in 30 cats with chronic gingivostomatitis and 32 healthy cats. The cats with chronic gingivostomatitis had significantly higher salivary concentrations of IgG, IgM and albumin, and higher serum concentrations of IgG, IgM and IgA, but significantly lower salivary concentrations of IgA than the healthy cats. The cats with chronic gingivostomatitis were treated with either methylprednisolone, sodium aurothiomalate, metronidazole and spiramycin, or oral hygiene products. After three months of treatment, the cats receiving methylprednisolone had a significant reduction in serum IgG levels compared to the cats treated with sodium aurothiomalate or metronidazole and spiramycin, but after six months of treatment there were no significant differences between the groups. Before the treatments, the levels of oral inflammation were not correlated significantly with any of the serum or salivary immunoglobulin levels. However, the changes in oral inflammation were correlated significantly with the changes in the salivary IgM concentration after three and six months of treatment, and with the change in the salivary IgA concentration after six months of treatment.

  1. [Immunoglobulins in the tear secretion in cases of herpetic keratitis].

    PubMed

    Malachi, A; Stan, C

    1999-01-01

    The goal of this study is to analyse the immunoglobulins of patients with herpetic keratitis. Tears have been collected from 36 patients with herpetic keratitis (study group) and 20 healthy volunteers (control group). Quantitative determination of A, G, M immunoglobulins and secretor IgA has been performed by Mancini radial immunodiffusion method. Our study has revealed the following results: a decrease in IgM and IgA levels compared with control group (p < 0.01) and an increase in secretory IgA compared with fellow eye (p < 0.05) in patients with herpetic keratitis of the first manifestation; eyes with recidivant herpetic keratitis showed higher level of IgA than the control group (p < 0.01) and a higher level of IgG than the first disease manifestation group (p < 0.05); the IgA level in the healthy eye of the patients with herpetic keratitis appeared significantly lower than in the control group (p < 0.001).

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

    PubMed

    Martel, Cyril Jean-Marie; Aasted, Bent

    2009-12-15

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

  3. Expression of cloned immunoglobulin genes introduced into mouse L cells.

    PubMed Central

    Gilles, S D; Tonegawa, S

    1983-01-01

    Functionally rearranged immunoglobulin heavy-chain (gamma 2b) and light-chain (lambda 1 and kappa) genes were introduced into mouse L tk- cells by co-transformation with the Herpes virus tk gene. Cloned cell lines were selected in HAT medium and tested for the presence of transfected immunoglobulin gene sequences by Southern blotting analysis. It was found that the gamma 2b gene was accurately transcribed at a low level in transfected mouse L cells and cytoplasmic gamma 2b, heavy-chain protein was detected by immunoprecipitation of cell extracts. Light-chain genes, on the other hand, were not accurately transcribed. Instead, lambda 1 or kappa RNA species were detected which were approximately 200 to 300 bases longer than the authentic mRNAs. These results suggest that the expression of rearranged heavy-chain and light-chain genes are controlled differently and that these differences can be seen in transfected, non-lymphoid cells. Images PMID:6316279

  4. The immunoglobulin light chain locus of the turkey, Meleagris gallopavo.

    PubMed

    Bao, Yonghua; Wu, Sun; Zang, Yunlong; Wang, Hui; Song, Xiangfeng; Xu, Chunyang; Xie, Bohong; Guo, Yongchen

    2012-06-15

    To date, most jawed vertebrate species encode more than one immunoglobulin light (IgL) chain isotypes. It has been shown that several bird species (chickens, white Pekin or domestic duck, and zebra finches) exclusively express lambda isotype. We analyze here the genomic organization of another bird species turkey IgL genes based on the recently released genome data. The turkey IgL locus located on chromosome 17 spans approximately 75.2kb and contains a single functional V(λ) gene, twenty V(λ) pseudogenes, and a single functional J(λ)-C(λ) block. These data suggest that the genomic organization of bird IgL chain genes seems to be conserved. Ten cDNA clones from turkey Igλ chain containing almost full-length V(λ), J(λ) and C(λ) segments were acquired. The comparison of V(λ) cDNA sequences to all the germline V(λ) segments suggests that turkey species may be generating IgL chain diversity by gene conversion and somatic hypermutation like the chicken. This study provides insights into the immunoglobulin light chain genes in another bird species. Copyright © 2012. Published by Elsevier B.V.

  5. 7th International Immunoglobulin Conference: Interlaken Leadership Awards.

    PubMed

    Dalakas, M C; Löscher, W N

    2014-12-01

    The Interlaken Leadership Awards (ILAs), established in 2010, are monetary grants pledged annually by CSL Behring to fund research into the use of immunoglobulin (Ig) therapy, especially into its use in neurological disorders. Five recipients of the 2011/2012 Awards were invited to present their research at the 7th International Immunoglobulin Conference. Dr Honnorat reports on paraneoplastic neurological syndromes (PNS). His multi-centre Phase II trial, currently under way, will assess the efficacy of IVIg therapy in treating PNS in the first 3 months of treatment. Dr Geis shows improved disease scores after IVIg treatment in a mouse model of neuromyelitis optica (NMO). It is hoped that these promising results will translate well into human NMO. Dr Schmidt studied IVIg therapy in an mdx mouse model for Duchenne muscular dystrophy (DMD). He reports that motor function improved and myopathic changes in skeletal muscles and creatine kinase release were decreased. Dr Gamez presents the design and rationale for a Phase II clinical trial investigating the preoperative use of IVIg therapy in myasthenia gravis patients to prevent post-operative myasthenic crisis. Dr Goebel reports results from studies elucidating the immune-mediated pathogenesis of complex regional pain syndrome (CRPS), the successful IVIg therapy in a proportion of CRPS patients, and the development of a model for predicting which patients are more likely to respond to Ig therapy.

  6. Immunoglobulin G Expression in Human Sperm and Possible Functional Significance

    PubMed Central

    Yan, Meiling; Zhang, Xiaoyu; Pu, Qinxue; Huang, Tao; Xie, Qingdong; Wang, Yan; Li, Jing; Wang, Yun; Gu, Huan; Huang, Tianhua; Li, Zhiling; Gu, Jiang

    2016-01-01

    Immunoglobulin G (IgG), the major molecule of the immune system, which was traditionally thought to be produced by differentiated B-lymphocytes, had recently been found in non-immune cells including spermatozoa of rabbit testis. To study if human sperms could produce IgG that might play a role in fertilization, we employed immunofluorescent staining, Western blot, in situ hybridization, RT-PCR (reverse transcription polymerase chain reaction) and immunoelectron microscope and found that human sperms were capable of synthesizing IgG. IgG protein and mRNA were detected in the cytoplasm, mainly the neck region of the sperm and IgG immunoreactivity was found to cover the entire sperm cell. The essential enzymes necessary for IgG synthesis and class switching, RAG1 (recombination activating gene 1), RAG2 (recombination activating gene 2) and AID (activation-induced cytidine deaminase), were also detected in the sperm cells. Furthermore, we found that anti-IgG antibody could inhibit sperm from penetrating Zona-free hamster egg with statistical significance. These discoveries suggested that immunoglobulin G could be produced by human sperms and it might play a role during fertilization. PMID:26833114

  7. Identification of an immunoglobulin Fc receptor of Actinobacillus actinomycetemcomitans.

    PubMed Central

    Mintz, K P; Fives-Taylor, P M

    1994-01-01

    Actinobacillus actinomycetemcomitans expresses proteins that bind to the Fc portion of immunoglobulins. The immunoglobulin Fc receptors on the surface of A. actinomycetemcomitans were detected by the binding of biotinylated human or murine Fc molecules to strain SUNY 465 adsorbed to the bottom of microtiter wells. Biotinylated Fc binding was inhibited by unlabeled Fc molecules and human plasma. Fc receptors were identified by the binding of biotinylated Fc molecules to bacterial membrane proteins separated by polyacrylamide gel electrophoresis and transferred to nitrocellulose. Multiple bands were identified, and the major Fc-binding protein was determined to be a heat-modifiable protein. This protein migrated with approximate molecular weights of 25,000 and 32,000 (unheated and heated, respectively). Amino-terminal sequence analysis of this protein revealed a sequence identical to the heat-modifiable protein described for A. actinomycetemcomitans ATCC 43718. This protein sequence exhibits significant homology with the N termini of outer membrane protein A (OmpA) of Escherichia coli and related OmpA-like proteins from other gram-negative bacteria. Images PMID:7927715

  8. Immunoglobulins and dietary protein antibodies in childhood coeliac disease 1

    PubMed Central

    Kenrick, K. G.; Walker-Smith, J. A.

    1970-01-01

    Twenty-four children with coeliac disease were compared with a control group, comprising 17 children with a variety of gastroenterological disorders, with respect to serum immunoglobulins and dietary protein antibodies. Elevated levels of IgA and abnormally low levels of IgM were demonstrated in one third of the coeliac patients. Antibodies to at least one of eight dietary proteins were found in 50% of coeliac children. Three children with raised levels of serum IgA and two with deficient IgM were re-examined after varying periods on a gluten-free diet. Antibodies to dietary proteins had waned and immunoglobulin levels returned to normal in all cases. The raised IgA was considered to have resulted from an extensive immunological response to antigens of dietary origin which had entered through the abnormal gut mucosa. It is suggested that IgM deficiency was due to specific inhibition of IgM synthesis by dietary components which had also entered through the mucosa. PMID:4097173

  9. The protective role of immunoglobulins in fungal infections and inflammation.

    PubMed

    Elluru, Sri Ramulu; Kaveri, Srini V; Bayry, Jagadeesh

    2015-03-01

    Increased incidence of fungal infections in the immunocompromised individuals and fungi-mediated allergy and inflammatory conditions in immunocompetent individuals is a cause of concern. Consequently, there is a need for efficient therapeutic alternatives to treat fungal infections and inflammation. Several studies have demonstrated that antibodies or immunoglobulins have a role in restricting the fungal burden and their clearance. However, based on the data from monoclonal antibodies, it is now evident that the efficacy of antibodies in fungal infections is dependent on epitope specificity, abundance of protective antibodies, and their isotype. Antibodies confer protection against fungal infections by multiple mechanisms that include direct neutralization of fungi and their antigens, inhibition of growth of fungi, modification of gene expression, signaling and lipid metabolism, causing iron starvation, inhibition of polysaccharide release, and biofilm formation. Antibodies promote opsonization of fungi and their phagocytosis, complement activation, and antibody-dependent cell toxicity. Passive administration of specific protective monoclonal antibodies could also prove to be beneficial in drug resistance cases, to reduce the dosage and associated toxic symptoms of anti-fungal drugs. The longer half-life of the antibodies and flexibilities to modify their structure/forms are additional advantages. The clinical data obtained with two monoclonal antibodies should incite interests in translating pre-clinical success into the clinics. The anti-inflammatory and immunoregulatory role of antibodies in fungal inflammation could be exploited by intravenous immunoglobulin or IVIg.

  10. 7th International Immunoglobulin Conference: Mechanisms of action.

    PubMed

    Basta, M; Branch, D R

    2014-12-01

    Although intravenous immunoglobulin (IVIg) is widely used for replacement therapy in immunodeficiencies and to treat autoimmune and inflammatory diseases, its mechanisms of action are not fully understood. Examination of immunoglobulin (Ig) receptors, including the Fc-gamma receptors (FCγRs) and the neonatal Fc receptor, have revealed genetic variations that are linked to autoimmune diseases and to the efficacy of IVIg treatment. However, the beneficial effect of IVIg encompasses multiple mechanisms of action. One of these is scavenging of activated complement fragments, such as C3a, C5a, C3b and C4b, by infused Ig molecules. This interaction prevents binding of complement fragments to their receptors on target cells, thus attenuating the immune damage. Additionally, anti-inflammatory effects may be facilitated by IgA via specific receptors and/or complement scavenging. Glycosylation of both the Fc- and Fab-fragments has also been implicated in the anti-inflammatory action of IVIg. Although there is evidence to support a role for sialylated IgG glycovariants in mediating the effect of IVIg, evidence from animal models of inflammatory disease suggest that sialylation may not be a critical factor. However, an increase in IgG glycosylation has been observed following IVIg treatment in Guillain-Barré syndrome patients, and this has been associated with improved clinical outcomes.

  11. Evaluation of serum immunoglobulin E levels in bronchial asthma

    PubMed Central

    Sandeep, Thirunavukkarasu; Roopakala, Mysore Subrahmanyam; Silvia, Chickballapur Rayappa Wilma Delphine; Chandrashekara, Srikantaiah; Rao, Mohan

    2010-01-01

    Background: Immunoglobulin E and associated cellular responses are responsible for allergic airway diseases. A hypersensitivity reaction initiated by immunologic mechanisms, mediated by IgE antibodies occurs in allergic asthma Aim: To estimate and compare serum IgE levels in mild, moderate, and severe asthmatics and in normal subjects and to obtain a mathematical model describing the relationship between serum IgE levels and severity of asthma. Materials and Methods: A stratified sample of 60 patients within age group of 18-60 years and 31 male and 29 female asthmatic patients and 13 healthy controls within 18-60 years were included in this study and classified according to GINA classification. Serum IgE levels were estimated by using ELISA kit. Results: Mean IgE levels ranged from 151.95 IU/ml in normal subjects to 1045.32 IU/ml in severe asthmatics. The model developed was 27% efficient. Conclusion: Serum Immunoglobulin E levels were high in asthmatics as compared to normal subjects. On an average, the levels increased as the severity of asthma increased. However, there was no statistically significant correlation since the variability in each level of asthma was very large PMID:20931031

  12. Therapeutic Potential of Intravenous Immunoglobulin in Acute Brain Injury

    PubMed Central

    Thom, Vivien; Arumugam, Thiruma V.; Magnus, Tim; Gelderblom, Mathias

    2017-01-01

    Acute ischemic and traumatic injury of the central nervous system (CNS) is known to induce a cascade of inflammatory events that lead to secondary tissue damage. In particular, the sterile inflammatory response in stroke has been intensively investigated in the last decade, and numerous experimental studies demonstrated the neuroprotective potential of a targeted modulation of the immune system. Among the investigated immunomodulatory agents, intravenous immunoglobulin (IVIg) stand out due to their beneficial therapeutic potential in experimental stroke as well as several other experimental models of acute brain injuries, which are characterized by a rapidly evolving sterile inflammatory response, e.g., trauma, subarachnoid hemorrhage. IVIg are therapeutic preparations of polyclonal immunoglobulin G, extracted from the plasma of thousands of donors. In clinical practice, IVIg are the treatment of choice for diverse autoimmune diseases and various mechanisms of action have been proposed. Only recently, several experimental studies implicated a therapeutic potential of IVIg even in models of acute CNS injury, and suggested that the immune system as well as neuronal cells can directly be targeted by IVIg. This review gives further insight into the role of secondary inflammation in acute brain injury with an emphasis on stroke and investigates the therapeutic potential of IVIg. PMID:28824617

  13. Human immunoglobulin G levels of viruses and associated glioma risk.

    PubMed

    Sjöström, Sara; Hjalmars, Ulf; Juto, Per; Wadell, Göran; Hallmans, Göran; Tjönneland, Anne; Halkjaer, Jytte; Manjer, Jonas; Almquist, Martin; Melin, Beatrice S

    2011-09-01

    Few consistent etiological factors have been identified for primary brain tumors. Inverse associations to asthma and low levels of varicella-zoster virus, immunoglobulin (Ig) levels in prevalent cases have indicted a role for the immune system in the development of glioma. Because samples from prevalent cases of glioma could be influenced by treatments such as steroids and chemotherapy, we investigated pre-diagnostic samples from three large Scandinavian cohorts. To test the hypothesis that immune response levels to these viruses are associated etiologically with glioma risk, we investigated pre-diagnostic immunoglobulin levels for cytomegalovirus (CMV), varicella-zoster virus (VZV), adenovirus (Ad), and Epstein-Barr virus (EBV) including the nuclear antigen (EBNA1) using plasma samples from 197 cases of adult glioma and 394 controls collected from population-based cohorts in Sweden and Denmark. Low VZV IgG levels were marginally significantly more common in glioma cases than the controls (odds ratio (OR) = 0.68, 95% CI 0.41-1.13) for the fourth compared with the first quartile (p = 0.06 for trend). These results were more prominent when analyzing cases with blood sampling at least 2 years before diagnosis (OR = 0.63, 95% CI 0.37-1.08) (p = 0.03). No association with glioma risk was observed for CMV, EBV, and adenovirus.

  14. Biallelic Germline Transcription at the κ Immunoglobulin Locus

    PubMed Central

    Singh, Nandita; Bergman, Yehudit; Cedar, Howard; Chess, Andrew

    2003-01-01

    Rearrangement of antigen receptor genes generates a vast array of antigen receptors on lymphocytes. The establishment of allelic exclusion in immunoglobulin genes requires differential treatment of the two sequence identical alleles. In the case of the κ immunoglobulin locus, changes in chromatin structure, methylation, and replication timing of the two alleles are all potentially involved in regulating rearrangement. Additionally, germline transcription of the κ locus which precedes rearrangement has been proposed to reflect an opening of the chromatin structure rendering it available for rearrangement. As the initial restriction of rearrangement to one allele is critical to the establishment of allelic exclusion, a key question is whether or not germline transcription at the κ locus is monoallelic or biallelic. We have used a sensitive reverse transcription-polymerase chain reaction (RT-PCR) assay and an RNA–fluorescence in situ hybridization (FISH) to show that germline transcription of the κ locus is biallelic in wild-type immature B cells and in recombination activating gene (RAG)−/−, μ+ B cells. Therefore, germline transcription is unlikely to dictate which allele will be rearranged first and rather reflects a general opening on both alleles that must be accompanied by a mechanism allowing one of the two alleles to be rearranged first. PMID:12629064

  15. Somatic mutation of immunoglobulin VH6 genes in human infants

    PubMed Central

    Ridings, J; Dinan, L; Williams, R; Roberton, D; Zola, H

    1998-01-01

    Infants respond to antigen by making antibody that is generally of low affinity for antigen. Somatic hypermutation of immunoglobulin genes, and selection of cells expressing mutations with improved affinity for antigen, are the molecular and cellular processes underlying the maturation of antibody affinity. We have reported previously that neonates and infants up to 2 months of age, including individuals undergoing strong immunological challenge, show very few mutated VH6 sequences, with low mutation frequencies in mutated sequences, and little evidence of selection. We have now examined immunoglobulin genes from healthy infants between 2 and 10 months old for mutation and evidence of selection. In this age group, the proportion of VH6 sequences which are mutated and the mutation frequency in mutated sequences increase with age. There is evidence of selection from 6 months old. These results indicate that the process of affinity maturation, which depends on cognate T–B cell interaction and functional germinal centres, is approaching maturity from 6 months old. PMID:9764600

  16. High-resolution physicochemical characterization of different intravenous immunoglobulin products.

    PubMed

    Washburn, Nathaniel; Meccariello, Robin; Hu, Shaohui; Hains, Maurice; Bhatnagar, Naveen; Sarvaiya, Hetal; Kapoor, Bulbul; Schaeck, John; Pino, Ignacio; Manning, Anthony; Lansing, Jonathan C; Bosques, Carlos J

    2017-01-01

    Intravenous immunoglobulin (IVIg) is a complex mixture drug comprising diverse immunoglobulins and non-IgG proteins purified from the plasma of thousands of healthy donors. Approved IVIg products on the market differ regarding source of plasma, isolation process, and formulation. These products are used widely, and often interchangeably, for the treatment of immunodeficiency and autoimmune and inflammatory diseases, but their mechanisms of action in different indications are not well understood. A primary limitation to understanding the therapeutic relevance of specific components within IVIg has been the limited resolution of analytics historically implemented to characterize its complex mixture. In this study, high-resolution analytics were applied to better understand the composition of IVIg and product variations. We characterized three approved IVIg products: Gammagard®, Privigen®, and Octagam®. Differences in the distribution of molecular weight species, IgG sequence variants, isoforms, glycoforms, and the repertoire of previously reported antibody specificities were identified. We also compared the effect of aging on these products to identify changes in size distribution and posttranslational modifications. This type of characterization may provide insights into the specific factors and components of IVIg that may influence its activity and ultimately lead to optimization of IVIg products for use in autoimmune diseases.

  17. High-resolution physicochemical characterization of different intravenous immunoglobulin products

    PubMed Central

    Washburn, Nathaniel; Meccariello, Robin; Hu, Shaohui; Hains, Maurice; Bhatnagar, Naveen; Sarvaiya, Hetal; Kapoor, Bulbul; Schaeck, John; Pino, Ignacio; Manning, Anthony; Lansing, Jonathan C.

    2017-01-01

    Intravenous immunoglobulin (IVIg) is a complex mixture drug comprising diverse immunoglobulins and non–IgG proteins purified from the plasma of thousands of healthy donors. Approved IVIg products on the market differ regarding source of plasma, isolation process, and formulation. These products are used widely, and often interchangeably, for the treatment of immunodeficiency and autoimmune and inflammatory diseases, but their mechanisms of action in different indications are not well understood. A primary limitation to understanding the therapeutic relevance of specific components within IVIg has been the limited resolution of analytics historically implemented to characterize its complex mixture. In this study, high-resolution analytics were applied to better understand the composition of IVIg and product variations. We characterized three approved IVIg products: Gammagard®, Privigen®, and Octagam®. Differences in the distribution of molecular weight species, IgG sequence variants, isoforms, glycoforms, and the repertoire of previously reported antibody specificities were identified. We also compared the effect of aging on these products to identify changes in size distribution and posttranslational modifications. This type of characterization may provide insights into the specific factors and components of IVIg that may influence its activity and ultimately lead to optimization of IVIg products for use in autoimmune diseases. PMID:28759653

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

    PubMed

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

    2011-08-15

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

  19. Immunological Studies of the Human Placenta CHARACTERIZATION OF IMMUNOGLOBULINS ON TROPHOBLASTIC BASEMENT MEMBRANES

    PubMed Central

    Faulk, W. Page; Jeannet, M.; Creighton, W. D.; Carbonara, A.

    1974-01-01

    Immunohistological and elution studies of the human placenta revealed the presence of IgG on the trophoblastic basement membrane (TBM) which demonstrated specificity for placental but not lung, thyroid, or kidney basement membranes, suggesting the presence of a placenta-specific antigen in TBM. IgG comprised the bulk of immunoglobulin in eluates, and small amounts of IgA, trace amounts of IgM, but no IgE or IgD were identified in eluates. The distribution of IgG subclasses in eluate was not unusual as compared to maternal and neonatal sera, and Gm and Inv typing of eluates indicated that it was of maternal origin. Small amounts of eluate-IgG effectively inhibited the blastogenic response of unrelated lymphocytes to old tuberculin, phytohemagglutinin, and in one- or two-way mixed lymphocyte culture reactions. The inhibition was distinct from nonspecific inhibitors, and dose-response analysis indicated that eluate was very much more potent as an inhibitor than were the nonspecific inhibitors. Inhibition was shown to not be due to anti-HL-A activity, and was probably not due to aggregated IgG or immune complexes. Binding of eluate to lymphocytes was very loose as shown by washing experiments, and no binding could be shown by immunofluorescence. The capacity of eluate IgG to inhibit MLC was retained after pepsin digestion to F(ab′)2, suggesting that the inhibition reactions were immunological. It is suggested that eluate-IgG is maternal blocking antibody to a hitherto uncharacterized trophoblast antigen, and it is speculated that either abnormal antigen or aberrant responses to antigen could result in fetal wastage. Images PMID:4278853

  20. A Comparative Study of Intravenous Immunoglobulin and Subcutaneous Immunoglobulin in Adult Patients with Primary Immunodeficiency Diseases: A Systematic Review and Meta-Analysis.

    PubMed

    Shabaninejad, Hosein; Asgharzadeh, Asra; Rezaei, Nima; Rezapoor, Aziz

    2016-01-01

    Subcutaneous immunoglobulin (SCIG) is a new therapeutic procedure for patients with primary immunodeficiency (PI). This research is a systematic review of studies on the efficacy and safety of intravenous immunoglobulin (IVIG) and SCIG in adult patients with PI. This study includes a systematic review of cohorts and randomized clinical trials (24 articles) from 5 databases with no time limits. Random effects meta-analysis was performed for outcomes such as efficacy and safety. Standard mean difference (SMD) of serum immunoglobulin level was equal to 0.336 (P <0.01; 0.205-0.467) and the odds ratio (OR) of side effects was 0.497 (P=0.1; 0.180-1.371). The results indicate that SCIG leads to a higher level of immunoglobulin and a reduction in side effects but shows the same infection rate as IVIG. Our analysis shows that shifting from IVIG to SCIG therapy can have clinical benefits for PI patients.

  1. Immunoglobulin M-enriched intravenous polyclonal immunoglobulins reduce bacteremia following Klebsiella pneumoniae infection in an acute respiratory distress syndrome rat model.

    PubMed

    Lachmann, R A; van Kaam, A H L C; Haitsma, J J; Verbrugge, S J C; Delreu, F; Lachmann, B

    2004-06-01

    Mechanical ventilation is known to induce bacterial translocation from the lung into the systemic circulation. This study determined the effect of immunoglobulin M (IgM)-enriched polyclonal immunoglobulins on bacteremia due to ventilation-induced translocation in an acute respiratory distress syndrome (ARDS) rat model with Klebsiella-induced pneumonia. After whole lung lavage, Sprague-Dawley rats intravenously received either a high dose or a low dose of an immunoglobulin preparation, or an albumin solution as control, followed by an intratracheal injection of a Klebsiella pneumoniae solution. Blood colony-forming units (CFUs) in the treatment groups were significantly lower during the 3-hour ventilation period compared to the control group. The authors conclude that IgM-enriched polyclonal immunoglobulins lead to a reduction of bacteria in blood of surfactant-deficient, ventilated rats infected with Klebsiella pneumoniae.

  2. Investigating the mechanisms leading to protein aggregation

    NASA Astrophysics Data System (ADS)

    McNamara, Ruth; McManus, Jennifer J.

    2014-03-01

    The formation of protein aggregates is a feature of several diseases and is a problem during the manufacture of biopharmaceutical and protein based food products. During processing, stability may become compromised leading to the condensation of proteins to form non-native aggregates. The aim of this work is to induce aggregation on model proteins by the imposition of a particular stress to evaluate the extent of aggregation and to assess the degree of structural change to the protein. Aggregation of two proteins, lysozyme and bovine serum albumin has been induced by several mechanisms. Using various techniques (electrophoresis, HPLC, spectroscopic analysis, and microscopic techniques) both the level of aggregation extent of protein unfolding has been investigated for a range of solution conditions. Our results show that the amount of aggregation depends strongly on the mechanism by which non-native aggregation proceeds, and within each mechanism, solution conditions are an important factor. With the exception of aggregation by self-association (which is concentration dependent), the appearance of aggregation is driven by structural changes induced by the applied stress (heat, chemical denaturant, oxidation or contact with a surface). Author would like to acknowledge support from Science Foundation Ireland (SFI), National University of Maynooth John and Pat Hume Scholarship.

  3. Applications of aggregation theory to sustainability assessment

    DOE PAGES

    Pollesch, N.; Dale, V. H.

    2015-04-01

    In order to aid in transition towards operations that promote sustainability goals, researchers and stakeholders use sustainability assessments. Although assessments take various forms, many utilize diverse sets of indicators that can number anywhere from two to over 2000. Indices, composite indicators, or aggregate values are used to simplify high dimensional and complex data sets and to clarify assessment results. Although the choice of aggregation function is a key component in the development of the assessment, there are few examples to be found in literature to guide appropriate aggregation function selection. This paper develops a connection between the mathematical study ofmore » aggregation functions and sustainability assessment in order to aid in providing criteria for aggregation function selection. Relevant mathematical properties of aggregation functions are presented and interpreted. Lastly, we provide cases of these properties and their relation to previous sustainability assessment research. Examples show that mathematical aggregation properties can be used to address the topics of compensatory behavior and weak versus strong sustainability, aggregation of data under varying units of measurements, multiple site multiple indicator aggregation, and the determination of error bounds in aggregate output for normalized and non-normalized indicator measures.« less

  4. Applications of aggregation theory to sustainability assessment

    SciTech Connect

    Pollesch, N.; Dale, V. H.

    2015-04-01

    In order to aid in transition towards operations that promote sustainability goals, researchers and stakeholders use sustainability assessments. Although assessments take various forms, many utilize diverse sets of indicators that can number anywhere from two to over 2000. Indices, composite indicators, or aggregate values are used to simplify high dimensional and complex data sets and to clarify assessment results. Although the choice of aggregation function is a key component in the development of the assessment, there are few examples to be found in literature to guide appropriate aggregation function selection. This paper develops a connection between the mathematical study of aggregation functions and sustainability assessment in order to aid in providing criteria for aggregation function selection. Relevant mathematical properties of aggregation functions are presented and interpreted. Lastly, we provide cases of these properties and their relation to previous sustainability assessment research. Examples show that mathematical aggregation properties can be used to address the topics of compensatory behavior and weak versus strong sustainability, aggregation of data under varying units of measurements, multiple site multiple indicator aggregation, and the determination of error bounds in aggregate output for normalized and non-normalized indicator measures.

  5. Pyridine Aggregation in Helium Nanodroplets

    NASA Astrophysics Data System (ADS)

    Nieto, Pablo; Poerschke, Torsten; Habig, Daniel; Schwaab, Gerhard; Havenith, Martina

    2012-06-01

    Pyridine crystals show the unusual property of isotopic polymorphism. Experimentally it has been observed that deuterated pyridine crystals exist in two phases while non-deuterated pyridine does not show a phase transition. Therefore, although isotopic substitution is the smallest possible modification of a molecule it greatly affects the stability of pyridine crystals. A possible experimental approach in order to understand this striking effect might be the study of pyridine aggregation for small clusters. By embedding the clusters in helium nanodroplets the aggregates can be stabilized and studied by means of Infrared Depletion Spectroscopy. Pyridine oligomers were investigated in the C-H asymmetric vibration region (2980-3100 cm-1) using this experimental technique. The number of molecules for the clusters responsibles for each band were determined by means of pick-up curves as well as mass sensitive depletion spectra. Furthermore, the intensity dependence of the different bands on applying a dc electric field was studied. The assignment of the different structures for pyridine clusters on the basis of these measurements were also carried out. S. Crawford et al., Angew. Chem. Int. Ed., 48, 755 (2009).

  6. Asphaltene aggregation in organic solvents.

    PubMed

    Oh, Kyeongseok; Ring, Terry A; Deo, Milind D

    2004-03-01

    Asphaltenic solids formed in the Rangely field in the course of a carbon dioxide flood and heptane insolubles in the oil from the same field were used in this study. Four different solvents were used to dissolve the asphaltenes. Near-infrared (NIR) spectroscopy was used to determine the onset of asphaltene precipitation by heptane titration. When the onset values were plotted versus asphaltene concentrations, distinct break points (called critical aggregation concentrations (CAC) in this paper) were observed. CACs for the field asphaltenes dissolved in toluene, trichloroethylene, tetrahydrofuran, and pyridine occurred at concentrations of 3.0, 3.7, 5.0, and 8.2 g/l, respectively. CACs are observed at similar concentrations as critical micelle concentrations (CMC) for the asphaltenes in the solvents employed and can be interpreted to be the points at which rates of asphaltene aggregations change. CMC values of asphaltenes determined from surface tension measurements (in pyridine and TCE) were slightly higher than the CAC values measured by NIR onset measurements. The CAC for heptane-insoluble asphaltenes in toluene was 3.1 g/l. Thermal gravimetric analysis (TGA) and elemental compositions of the two asphaltenes showed that the H/C ratio of the heptane-insoluble asphaltenes was higher and molecular weight (measured by vapor pressure osmometry) was lower.

  7. Sectoral shifts and aggregate unemployment

    SciTech Connect

    Loungani, P.

    1986-01-01

    Some recent research has taken the view that sectoral or industry-specific shocks significantly affect aggregate unemployment by increasing the amount of inter-industry labor reallocation required. The empirical evidence for this view rests on the finding that during the 1950s - and again during the 1970s - there was a positive correlation between aggregate unemployment and the dispersion of employment growth rates. This thesis demonstrates that this correlation arises largely because oil price shocks affect both unemployment and the dispersion of employment growth. Once the dispersion due to oil shocks is accounted for, the residual dispersion in employment has very low explanatory power for unemployment. Since the dispersion index does not measure pure sectoral shifts, an alternate measure of dispersion is developed that serves as a better proxy for the amount of inter-industry labor reallocation required each period. Estimates using this measure suggest that, during the 1950s, temporary increases in the relative price of oil were responsible for generating the observed correlation. On the other hand, sectoral shifts were important during the 1970s; in particular, the 1973 oil price increase has had significant reallocative effects on the economy. This contention is subjected to further tests by looking at the time-series behavior of employment in durable-goods industries and also by following the inter-industry movements of workers over time through the use of panel data.

  8. Does thermophoresis reduce aggregate stability?

    NASA Astrophysics Data System (ADS)

    Sachs, Eyal; Sarah, Pariente

    2017-04-01

    Thermophoresis is mass flow driven by a thermal gradient. As a result of Seebeck effect and Soret effect, colloids can move from the hot to the cold region or vice versa, depending on the electrolyte composition and on the particle size. This migration of colloids can weaken aggregates. The effect of raindrop temperatures on runoff generation and erosion on clayey soil was investigated in sprinkling experiments with a laboratory rotating disk rain simulator. The experiments were applied to Rhodoxeralt (Terra Rossa) soil with two pre-prepared moisture contents: hygroscopic and field capacity. For each moisture content three rainfall temperatures were applied: 2, 20, and 35°C. Erosion was generally lower in the pre-wetted soil than in the dry soil (12.5 and 24.4 g m-2 per 40 mm of rain,respectively). Whereas there was no significant effect of raindrop temperature on the dry soil the soil that was pre-moistened to field capacity was affected by rainwater temperature: runoff and erosion were high when the temperature difference between rainfall and soil surface was high, sediment yields were 13.9, 5.2, and 18.3 g m-2 per 40 mm of rain, for rain temperature of 2, 20, and 35 °C, respectively. It is reasonable to conclude that thermophoresis caused by thermal gradients within the soil solution reduces the stability of aggregates and then increase the soil losses.

  9. Role of Multicellular Aggregates in Biofilm Formation

    PubMed Central

    Kragh, Kasper N.; Hutchison, Jaime B.; Melaugh, Gavin; Rodesney, Chris; Roberts, Aled E. L.; Irie, Yasuhiko; Jensen, Peter Ø.; Diggle, Stephen P.; Allen, Rosalind J.

    2016-01-01

    ABSTRACT In traditional models of in vitro biofilm development, individual bacterial cells seed a surface, multiply, and mature into multicellular, three-dimensional structures. Much research has been devoted to elucidating the mechanisms governing the initial attachment of single cells to surfaces. However, in natural environments and during infection, bacterial cells tend to clump as multicellular aggregates, and biofilms can also slough off aggregates as a part of the dispersal process. This makes it likely that biofilms are often seeded by aggregates and single cells, yet how these aggregates impact biofilm initiation and development is not known. Here we use a combination of experimental and computational approaches to determine the relative fitness of single cells and preformed aggregates during early development of Pseudomonas aeruginosa biofilms. We find that the relative fitness of aggregates depends markedly on the density of surrounding single cells, i.e., the level of competition for growth resources. When competition between aggregates and single cells is low, an aggregate has a growth disadvantage because the aggregate interior has poor access to growth resources. However, if competition is high, aggregates exhibit higher fitness, because extending vertically above the surface gives cells at the top of aggregates better access to growth resources. Other advantages of seeding by aggregates, such as earlier switching to a biofilm-like phenotype and enhanced resilience toward antibiotics and immune response, may add to this ecological benefit. Our findings suggest that current models of biofilm formation should be reconsidered to incorporate the role of aggregates in biofilm initiation. PMID:27006463

  10. Oral Human Immunoglobulin for Children with Autism and Gastrointestinal Dysfunction: A Prospective, Open-Label Study

    ERIC Educational Resources Information Center

    Schneider, Cindy K.; Melmed, Raun D.; Barstow, Leon E.; Enriquez, F. Javier; Ranger-Moore, James; Ostrem, James A.

    2006-01-01

    Immunoglobulin secretion onto mucosal surfaces is a major component of the mucosal immune system. We hypothesized that chronic gastrointestinal (GI) disturbances associated with autistic disorder (AD) may be due to an underlying deficiency in mucosal immunity, and that orally administered immunoglobulin would be effective in alleviating chronic GI…

  11. Decreased immunoglobulin E (IgE) binding to cashew allergens following sodium sulfite treatment and heating

    USDA-ARS?s Scientific Manuscript database

    Cashew nut and other nut allergies can result in serious and sometimes life threatening reactions. Linear and conformational epitopes within food allergens are important for immunoglobulin E binding. Methods that disrupt allergen structure can reduce immunoglobulin E binding and lessen the likelih...

  12. Postpartum Treatment With Immunoglobulin Does Not Prevent Relapses of Multiple Sclerosis in the Mother.

    PubMed

    Fragoso, Yara Dadalti; Adoni, Tarso; Alves-Leon, Soniza Vieira; Azambuja, Nerio Dutra; Barreira, Amilton Antunes; Brooks, Joseph Bruno Bidin; Carneiro, Denise Sisteroli Diniz; Carvalho, Margarete J; Claudino, Rinaldo; Comini-Frota, Elizabeth Regina; Domingues, Renan Barros; Finkelsztejn, Alessandro; Gama, Paulo Diniz; Giacomo, Maria Cristina Brandao; Gomes, Sidney; Goncalves, Marcus Vinicius Magno; Grzesiuk, Anderson Kuntz; Kaimen-Maciel, Damacio Ramon; Mendes, Maria Fernanda; Morales, Nivea Macedo Oliveira; Morales, Rogerio Rizo; Muniz, Andre; Papais-Alvarenga, Regina Maria; Parolin, Monica Koncke Fiuza; Ribeiro, Sonia Beatriz Felix; Ruocco, Heloisa Helena; Salgado, Pedro Rippel; Siquineli, Fabio; Souza, Doralina Brum; Tosta, Elza Dias; Vasconcelos, Claudia Cristina Ferreira; Almeida, Sandra Maria Garcia; Bernardes, Daniella Freire Ribeiro; Castro, Simone Nascimento; Gama, Rodrigo Assad Diniz; Gomide, Fabrizio Antonio Resende; Finkelzstejn, Juliana; Lopes, Josiane; Lourenco, Fabiani Honorato de Barros; Lourenco, Gisele A; Oliveira, Celso Luis Silva; Oliveira, Francisco Tomaz Meneses; Oliveira, Lucas Felix; Patroclo, Cristiane Borges; Pereira, Wildea Lice de Carvalho Jennings; Safanelli, Juliana; Sahdo, Alinne Martiniano; Saldanha, Patricia Correa de Oliveira; Shinzato, Yves Fumio; Souza, Jorge Murilo Barbosa; Zani, Denis Evandro

    2015-01-01

    Multiple sclerosis (MS) is a chronic, neurological, immune-mediated disease that can worsen in the postpartum period. There is no consensus on the use of immunoglobulin for prevention of disease relapses after delivery. We have shown that the controversial beneficial effect of immunoglobulin given immediately after birth could not be observed in patients with MS.

  13. Oral Human Immunoglobulin for Children with Autism and Gastrointestinal Dysfunction: A Prospective, Open-Label Study

    ERIC Educational Resources Information Center

    Schneider, Cindy K.; Melmed, Raun D.; Barstow, Leon E.; Enriquez, F. Javier; Ranger-Moore, James; Ostrem, James A.

    2006-01-01

    Immunoglobulin secretion onto mucosal surfaces is a major component of the mucosal immune system. We hypothesized that chronic gastrointestinal (GI) disturbances associated with autistic disorder (AD) may be due to an underlying deficiency in mucosal immunity, and that orally administered immunoglobulin would be effective in alleviating chronic GI…

  14. Immunoglobulin K light chain deficiency: A rare, but probably underestimated, humoral immune defect.

    PubMed

    Sala, Pierguido; Colatutto, Antonio; Fabbro, Dora; Mariuzzi, Laura; Marzinotto, Stefania; Toffoletto, Barbara; Perosa, Anna R; Damante, Giuseppe

    2016-04-01

    Human immunoglobulin molecules are generated by a pair of identical heavy chains, which identify the immunoglobulin class, and a pair of identical light chains, Kappa or Lambda alternatively, which characterize the immunoglobulin type. In normal conditions, Kappa light chains represent approximately 2/3 of the light chains of total immunoglobulins, both circulating and lymphocyte surface bound. Very few cases of immunoglobulin Kappa or Lambda light chain defects have been reported. Furthermore, the genetic basis of this defect has been extensively explored only in a single case. We report a case of a patient suffering of serious recurrent bacterial infections, which was caused by a very rare form of immunoglobulin disorder, consisting of a pure defect of Kappa light chain. We evaluated major serum immunoglobulin concentrations, as well as total and free Kappa and Lambda light chain concentrations. Lymphocyte phenotyping was also performed and finally we tested the Kappa chain VJ rearrangement as well as the constant Kappa region sequence. Studies performed on VJ rearrangement showed a polyclonal genetic arrangement, whereas the gene sequencing for the constant region of Kappa chain showed a homozygous T to G substitution at the position 1288 (rs200765148). This mutation causes a substitution from Cys to Gly in the protein sequence and, therefore, determines the abnormal folding of the constant region of Kappa chain. We suggest that this defect could lead to an effective reduction of the variability of total antibody repertoire and a consequent defect of an apparently normal immunoglobulin response to common antigens.

  15. 21 CFR 866.5540 - Immunoglobulin G (Fd fragment specific) immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin G (Fd fragment specific) immunological test system. 866.5540 Section 866.5540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... fragment) of the heavy chain (a subunit) of the immunoglobulin antibody molecule in serum. Measurement of...

  16. 21 CFR 866.5540 - Immunoglobulin G (Fd fragment specific) immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Immunoglobulin G (Fd fragment specific) immunological test system. 866.5540 Section 866.5540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... fragment) of the heavy chain (a subunit) of the immunoglobulin antibody molecule in serum. Measurement of...

  17. 21 CFR 866.5540 - Immunoglobulin G (Fd fragment specific) immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Immunoglobulin G (Fd fragment specific) immunological test system. 866.5540 Section 866.5540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... fragment) of the heavy chain (a subunit) of the immunoglobulin antibody molecule in serum. Measurement of...

  18. 21 CFR 866.5540 - Immunoglobulin G (Fd fragment specific) immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Immunoglobulin G (Fd fragment specific) immunological test system. 866.5540 Section 866.5540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... fragment) of the heavy chain (a subunit) of the immunoglobulin antibody molecule in serum. Measurement of...

  19. 21 CFR 866.5550 - Immunoglobulin (light chain specific) immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin (light chain specific) immunological test system. 866.5550 Section 866.5550 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Test Systems § 866.5550 Immunoglobulin (light chain specific) immunological test system....

  20. 21 CFR 866.5550 - Immunoglobulin (light chain specific) immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Immunoglobulin (light chain specific) immunological test system. 866.5550 Section 866.5550 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Test Systems § 866.5550 Immunoglobulin (light chain specific) immunological test system....