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Sample records for evading antibody avidity

  1. Quantitative relationship between antibody affinity and antibody avidity

    International Nuclear Information System (INIS)

    Griswold, W.R.

    1987-01-01

    The relationship between antibody avidity, measured by the dissociation of the antigen-antibody bond in antigen excess, and antibody affinity was studied. Complexes of radiolabelled antigen and antibody of known affinity were prepared in vitro and allowed to stand for seven days to reach equilibrium. Then nonlabelled antigen in one hundred fold excess was added to dissociate the complexes. After an appropriate incubation the fraction of antigen bound to antibody was measured by the ammonium sulfate precipitation method. The dissociation index was the fraction bound in the experimental sample divided by the fraction bound in the control. The correlation coefficient between the dissociation index and the antibody binding constant was 0.92 for early dissociation and 0.98 for late dissociation. The regression equation relating the binding constant to the dissociation index was K = 6.4(DI) + 6.25, where DI is the late dissociation index and K is the logarithm to the base 10 of the binding constant. There is a high correlation between avidity and affinity of antibody. Antibody affinity can be estimated from avidity data. The stability of antigen-antibody complexes can be predicted from antibody affinity

  2. In vitro measurement of avidity of radioiodinated antibodies

    International Nuclear Information System (INIS)

    Badger, C.C.; Krohn, K.A.; Bernstein, I.D.

    1987-01-01

    A determination of the ability of radiolabeled antibodies to bind to their target antigen is an essential step in the initial selection of antibodies for clinical use as well as a quality control measure. In our studies of the 131 I-labeled anti-Thy 1.1 antibody treatment of murine lymphoma, we have used cell binding assays with a combination of Lineweaver-Burk analysis to determine immunoreactivity and Scatchard analysis to determine antibody avidity. Both assays were systematically influenced by target cell fixation and measurement of avidity was dependent on immunoreactivity. For 131 I-labeled anti-Thy 1.1 antibody, avidity was a much more sensitive indicator of iodination damage and predictor of in vivo behavior than was immunoreactivity, while for other antibodies immunoreactivity has been a better indicator of labeling damage. Thus, immunoreactivity and avidity assays are complementary and knowledge of both factors is required for the design of sensitive quality control procedures for radiolabeled antibodies. (author)

  3. EPSTEIN-BARR VIRUS INFECTIONS – AVIDITY TEST FOR IgG ANTIBODIES

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    Katja Strašek

    2001-06-01

    Full Text Available Background. We wish to introduce specific IgG avidity test as a supplementary assay in serological screening for Epstein-Barr virus infection if the status of patient cannot be resolved from a single serum sample with routine testing.Methods. Avidity of IgG antibodies was determined in sera of 57 patients with different stage of Epstein-Barr virus infection. Enzyme-immuno assay was used with a short incubation of 6-molar urea included in the procedure. Urea should remove low avidity antibodies. Avidity was expressed as the avidity index. Avidity testing with commercial kit was done as well.Results. Low avidity index was found for IgG antibodies of acute phase sera and high for those of past infection, recent infection and reactivation of endogenic virus.Conclusions. Avidity test for IgG antibodies might be supplementary assay to prove acute infection but also to resolve some other clinical states related to Epstein-Barr virus.

  4. AVIDITY EVALUATION OF LOCAL IgA ANTIBODIES IN PERSONS IMMUNIZED WITH LIVE INFLUENZA VACCINE

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    S. A. Donina

    2008-01-01

    Full Text Available Abstract. At present, immunogenicity evaluation of influenza vaccines is performed by quantitative assessment of increased serum antibodies. It was, however, shown that the degree of human defense against influenza is mostly related to their qualitative characteristics, i.e., avidity (functional activity. Leading role of local immunity is demonstrated in protection against influenza. Such immunity is mediated by IgA antibodies from mucosal airways. Meanwhile, the avidity issues for local antibodies still remain open.In present study, an attempt was undertaken to evaluate post-vaccination local immunological memory for influenza A virus, according to IgA antibodies from upper respiratory secretions. Two techniques were used to evaluate antibody avidity, that were previously applied for studying this phenomenon with serum imunoglobulins, i.e., a dynamic test (measurement of antigen-antibody reaction rates, and a test with urea, a chaotropic agent (avidity is determined as a strength of antigen-antibody complex. A total of 202 persons (18 to 20 years old were enrolled into the study.With both tests, a broad range of individual avidity values was observed for the antibodies. A significant cohort (up to 30 per cent of persons immunized with live influenza vaccine, showed sharply increased avidity of secretory IgA antibodies by both methods, along with accumulation of these immunoglobulins after vaccination. A reverse relationship is revealed between avidity levels of these antibodies before vaccination, and increase of this parameter post-immunization. The data present convincing arguments for specific renewal of local humoral immunological memory, as induced by live influenza vaccine. The study substantiates a necessity for application of the both tests in parallel, when determining avidity of secretory IgA antibodies. (Med. Immunol., vol. 10, N 4-5, pp 423-430.

  5. Avidity of Antibodies against HSV-2 and Risk to Neonatal Transmission among Mexican Pregnant Women

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    Antonia Herrera-Ortiz

    2013-01-01

    Full Text Available Objective. To determine HSV-2 seroprevalence, risk factors, and antibody avidity among a sample of Mexican pregnant women. Material and Methods. The avidity test was standardized with different urea concentrations and incubation times; the cut-off point was calculated to determine the low avidity (early infection. IgG antibodies against HSV-2 were detected from pregnant and postpartum women from Morelos, Mexico, and the avidity test was performed to positive samples. Multivariate regression logistic analysis was employed to evaluate demographic and sexual behavior characteristics associated with HSV-2 infection. Results. HSV-2 seroprevalence among Mexican women analyzed was 14.5% (333/2300, demographic factors (location of General Hospital, age, education level, and civil status, and risky sexual behaviors (STI self-report and number of sexual partners during last year were associated with HSV-2 infection. Seventeen women were detected with low avidity antibodies (early infection with a cut-off point of 66.1%. Conclusions. HSV-2 infection was common among this group of women from Mexico; the avidity test detected women with recent infections, and these women were more likely to transmit HSV-2 to their neonates. Neonatal herpes has no epidemiological surveillance, the disease could be overlooked, and so more studies are needed to estimate the magnitude of neonatal infection.

  6. Porin A-specific antibody avidity in patients who are convalescing from meningococcal B disease.

    NARCIS (Netherlands)

    Vermont, C.L.; Dijken, H.H. van; Groot, R. de; Dobbelsteen, G.P. van den

    2005-01-01

    Porin A (PorA), which determines the serosubtype of Neisseria meningitidis, is the main antigen of a candidate vaccine against serogroup B meningococci, which has been shown to induce high-avidity antibodies in children. We characterized the immune response of children after convalescing from

  7. Avidity of anti-malarial antibodies inversely related to transmission intensity at three sites in Uganda.

    Science.gov (United States)

    Ssewanyana, Isaac; Arinaitwe, Emmanuel; Nankabirwa, Joaniter I; Yeka, Adoke; Sullivan, Richard; Kamya, Moses R; Rosenthal, Philip J; Dorsey, Grant; Mayanja-Kizza, Harriet; Drakeley, Chris; Greenhouse, Bryan; Tetteh, Kevin K A

    2017-02-10

    People living in malaria endemic areas acquire protection from severe malaria quickly, but protection from clinical disease and control of parasitaemia is acquired only after many years of repeated infections. Antibodies play a central role in protection from clinical disease; however, protective antibodies are slow to develop. This study sought to investigate the influence of Plasmodium falciparum exposure on the acquisition of high-avidity antibodies to P. falciparum antigens, which may be associated with protection. Cross-sectional surveys were performed in children and adults at three sites in Uganda with varied P. falciparum transmission intensity (entomological inoculation rates; 3.8, 26.6, and 125 infectious bites per person per year). Sandwich ELISA was used to measure antibody responses to two P. falciparum merozoite surface antigens: merozoite surface protein 1-19 (MSP1-19) and apical membrane antigen 1 (AMA1). In individuals with detectable antibody levels, guanidine hydrochloride (GuHCl) was added to measure the relative avidity of antibody responses by ELISA. Within a site, there were no significant differences in median antibody levels between the three age groups. Between sites, median antibody levels were generally higher in the higher transmission sites, with differences more apparent for AMA-1 and in ≥5 year group. Similarly, median avidity index (proportion of high avidity antibodies) showed no significant increase with increasing age but was significantly lower at sites of higher transmission amongst participants ≥5 years of age. Using 5 M GuHCl, the median avidity indices in the ≥5 year group at the highest and lowest transmission sites were 19.9 and 26.8, respectively (p = 0.0002) for MSP1-19 and 12.2 and 17.2 (p = 0.0007) for AMA1. Avidity to two different P. falciparum antigens was lower in areas of high transmission intensity compared to areas with lower transmission. Appreciation of the mechanisms behind these findings as

  8. Changes in avidity and level of immunoglobulin G antibodies to Mycobacterium tuberculosis in sera of patients undergoing treatment for pulmonary tuberculosis

    NARCIS (Netherlands)

    Arias-Bouda, Lenka M. Pereira; Kuijper, Sjoukje; van der Werf, Anouk; Nguyen, Lan N.; Jansen, Henk M.; Kolk, Arend H. J.

    2003-01-01

    Much is known about specific antibodies and their titers in patients with tuberculosis. However, little is known about the avidity of these antibodies or whether changes in avidity occur during the progression of the disease or during treatment. The aims of this study were to determine the avidity

  9. Characterization of Tumor-Avid Antibody Fragments Genetically Engineered for Mono-Specific Radionuclide Chelation

    International Nuclear Information System (INIS)

    Quinn, T.P.

    2003-01-01

    The successful clinical application of targeted-radiopharmaceuticals depends on the development of molecules that optimize tumor specific radionuclide deposition and minimize non-specific organ irradiation. To this end, this proposal outlines a research effort to identify and evaluate novel antibodies and antibody fragments that bind breast tumors. The tumor-avid antibodies will be investigated for as imaging and therapeutic agents and to gain a better understanding of the pharmacokinetics and metabolism of radiolabeled tumor-avid antibody fragments through the use of site-specifically labeled molecules. Antibodies or antibody fragments, that bind breast carcinoma carbohydrate antigens, will be obtained from hybridoma or bacteriophage library screening. More specifically, antibody fragments that bind the carcinoma-associated Thomsen-Friedenreich (T) antigen will be radiolabeled with 99m Tc and 188 Re at a natural amino acid chelation site and will be investigated in vivo for their abilities to target human breast tumors. In addition, site-specific radiolabeled antibody fragments will be biosynthesized using misacylated suppressor tRNAs. Homogeneously radiolabeled populations of antibody fragments will be used to investigate the effects of radionuclide location and chelation chemistries on their biodistribution and metabolism. It is hypothesized that site-specifically radiolabeled antibody fragments will possess enhanced tumor imaging and therapeutic properties due to optimal label location and conjugation chemistries. New insights into the factors that govern antibody metabolism in vivo are also expected from this work. Results from these studies should enhance our ability to design and synthesize radiolabeled antibody fragments that have improved pharmacokinetic properties. The studies in this proposal involve basic research into the development of antibody-based radiopharmaceuticals, with the ultimate goal of application in humans. This type of basic nuclear

  10. High avidity antibodies to full-length VAR2CSA correlate with absence of placental malaria.

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    Yeung Lo Tutterrow

    Full Text Available VAR2CSA mediates sequestration of Plasmodium falciparum-infected erythrocytes in the placenta, increasing the risk of poor pregnancy outcomes. Naturally acquired antibodies (Ab to placental parasites at delivery have been associated with improved pregnancy outcomes, but Ab levels and how early in pregnancy Ab must be present in order to eliminate placental parasites before delivery remains unknown. Antibodies to individual Duffy-binding like domains of VAR2CSA have been studied, but the domains lack many of the conformational epitopes present in full-length VAR2CSA (FV2. Thus, the purpose of this study was to describe the acquisition of Ab to FV2 in women residing in high and low transmission areas and determine how Ab levels during pregnancy correlate with clearance of placental parasites. Plasma samples collected monthly throughout pregnancy from pregnant women living in high and low transmission areas in Cameroon were evaluated for Ab to FV2 and the proportion of high avidity Ab (i.e., Ab that remain bound in the presence of 3M NH(4SCN was assessed. Ab levels and proportion of high avidity Ab were compared between women with placental malaria (PM(+ and those without (PM(- at delivery. Results showed that PM(- women had significantly higher Ab levels (p = 0.0047 and proportion of high avidity Ab (p = 0.0009 than PM(+ women throughout pregnancy. Specifically, women with moderate to high Ab levels (>5,000 MFI and those with ≥ 35% high avidity Ab at 5-6 months were found to have 2.3 (95% CI, 1.0-4.9 and 7.6-fold (p = 0.0013, 95% CI: 1.2-50.0 reduced risk of placental malaria, respectively. These data show that high levels of Ab to FV2, particularly those with high avidity for FV2, produced by mid-pregnancy are important in clearing parasites from the placenta. Both high Ab levels and proportion of high avidity Ab to FV2 may serve as correlates of protection for assessing immunity against placental malaria.

  11. Kinetic and HPV infection effects on cross-type neutralizing antibody and avidity responses induced by Cervarix®

    Science.gov (United States)

    Kemp, Troy J.; Safaeian, Mahboobeh; Hildesheim, Allan; Pan, Yuanji; Penrose, Kerri J.; Porras, Carolina; Schiller, John T.; Lowy, Douglas R.; Herrero, Rolando; Pinto, Ligia A.

    2012-01-01

    Background We previously demonstrated that Cervarix® elicits antibody responses against vaccine-related types for which clinical efficacy was demonstrated (HPV-31 and -45). Here, we evaluated the kinetics of neutralization titers and avidity of Cervarix®-induced antibodies up to 36 months of follow-up in unexposed and HPV infected women. Methods A subset of women who participated in the Cost Rica HPV-16/18 Vaccine Trial had pre- and post-vaccination sera tested for antibody responses to HPV-16, -18, -31, -45, and -58 using a pseudovirion-based neutralization assay, and HPV-16 antibody avidity using an HPV-16 L1 VLP (virus-like particle)-based ELISA developed in our laboratory. Results In uninfected women, neutralizing antibody titers did not reach significance until after the 3rd dose for HPV-31 (month 12, p=0.009) and HPV-45 (month 12, p=0.003), but then persisted up to month 36 (HPV-31, p=0.01; HPV-45, p=0.002). Individuals infected with HPV-16 or HPV-31 at enrollment developed a significantly higher median antibody response to the corresponding HPV type after one dose, but there was not a difference between median titers after three doses compared to the HPV negative group. Median HPV-16 antibody avidity and titer increased over time up to month 12; however, the HPV-16 avidity did not correlate well with HPV-16 neutralizing antibody titers at each time point examined, except for month 6. The median avidity levels were higher in HPV-16 infected women at month 1 (p=0.04) and lower in HPV-16 infected women at month 12 (p=0.006) compared to the HPV negative women. Conclusions The persistence of cross-neutralization titers at month 36 suggests cross-reactive antibody responses are likely to persist long-term and are not influenced by infection status at enrollment. However, the weak correlation between avidity and neutralization titers emphasizes the need for examining avidity in efficacy studies to determine if high avidity antibodies play a critical role in

  12. Interference of daratumumab with pretransfusion testing, mimicking a high-titer, low avidity like antibody

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    Mei-Hwa Lin

    2017-01-01

    Full Text Available Daratumumab is a monoclonal immunoglobulin against CD38 and has been approved for treating patients with refractory multiple myeloma. The presence of daratumumab in the sera can interfere with pretransfusion testing due to the weakly expression of CD38 on red cells. The reactivity could be mistaken as autoantibody (if autocontrol is positive or alloantibody (if autocontrol is negative. We present a case that demonstrates daratumumab could mimic a high titer low avidity (HTLA alloantibody. A 34-year-old male patient of refractory myeloma was recruited in phase three clinical trial involving daratumumab. Samples were sent to the blood bank for pretransfusion testing. Without knowledge of patient having used daratumumab, we mistook the reactivity in the patient's sera as an HTLA antibody due to the results of negative autocontrol and high titers of antibody activity. Antibody screen showed a panreactive pattern and the reactivity against screening cells was up to a titer of 1: 1240. The reactivity was weaker against cord cells than adult cells, became weaker against ZZAP-treated cells and became negative against DDT-treated cells. A discussion with attending physician finally revealed the reactivity was due to the interference caused by daratumumab. The case demonstrates good communication is essential in performing pretransfusion testing for patients receiving daratumumab and other new biological regimens that can interfere with compatibility test.

  13. Pregnancy does not affect HIV incidence test results obtained using the BED capture enzyme immunoassay or an antibody avidity assay.

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    Oliver Laeyendecker

    2010-10-01

    Full Text Available Accurate incidence estimates are needed for surveillance of the HIV epidemic. HIV surveillance occurs at maternal-child health clinics, but it is not known if pregnancy affects HIV incidence testing.We used the BED capture immunoassay (BED and an antibody avidity assay to test longitudinal samples from 51 HIV-infected Ugandan women infected with subtype A, C, D and intersubtype recombinant HIV who were enrolled in the HIVNET 012 trial (37 baseline samples collected near the time of delivery and 135 follow-up samples collected 3, 4 or 5 years later. Nineteen of 51 women were also pregnant at the time of one or more of the follow-up visits. The BED assay was performed according to the manufacturer's instructions. The avidity assay was performed using a Genetic Systems HIV-1/HIV-2 + O EIA using 0.1M diethylamine as the chaotropic agent.During the HIVNET 012 follow-up study, there was no difference in normalized optical density values (OD-n obtained with the BED assay or in the avidity test results (% when women were pregnant (n = 20 results compared to those obtained when women were not pregnant (n = 115; for BED: p = 0.9, generalized estimating equations model; for avidity: p = 0.7, Wilcoxon rank sum. In addition, BED and avidity results were almost exactly the same in longitudinal samples from the 18 women who were pregnant at only one study visit during the follow-up study (p = 0.6, paired t-test.These results from 51 Ugandan women suggest that any changes in the antibody response to HIV infection that occur during pregnancy are not sufficient to alter results obtained with the BED and avidity assays. Confirmation with larger studies and with other HIV subtypes is needed.

  14. Influence of maternal vaccination against diphtheria, tetanus, and pertussis on the avidity of infant antibody responses to a pertussis containing vaccine in Belgium.

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    Caboré, Raïssa Nadège; Maertens, Kirsten; Dobly, Alexandre; Leuridan, Elke; Van Damme, Pierre; Huygen, Kris

    2017-10-03

    Maternal antibodies induced by vaccination during pregnancy cross the placental barrier and can close the susceptibility gap to pertussis in young infants up to the start of primary immunization. As not only the quantity but also the quality of circulating antibodies is important for protection, we assessed whether maternal immunization affects the avidity of infant vaccine-induced IgG antibodies, in the frame of a prospective clinical trial on pregnancy vaccination in Belgium. Infants born from Tdap (Boostrix®) vaccinated (N = 55) and unvaccinated (N = 26) mothers were immunized with a hexavalent pertussis containing vaccine (Infanrix Hexa®) at 8, 12 and 16 weeks, followed by a fourth dose at 15 months of age. Right before and one month after this fourth vaccine dose, the avidity of IgG antibodies against diphtheria toxin (DT), tetanus toxin (TT), pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (Prn) was determined using 1.5 M ammonium thiocyanate as dissociating agent. In both groups, antibody avidity was moderate for TT, PT, FHA and Prn and low for DT after priming. After a fourth dose, antibody avidity increased significantly to high avidity for TT and PT, whereas it remained moderate for FHA and Prn and low for DT. The avidity correlated positively with antibody level in both study groups, yet not significantly for PT. When comparing both study groups, only PT-specific antibodies showed significantly lower avidity in infants born from vaccinated than from unvaccinated mothers after the fourth vaccine dose. The clinical significance of lower avidity of vaccine induced infant antibodies after maternal vaccination, if any, needs further investigation.

  15. High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases

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    Rota, Jennifer S.; Hickman, Carole J.; Mercader, Sara; Redd, Susan; McNall, Rebecca J.; Williams, Nobia; McGrew, Marcia; Walls, M. Laura; Rota, Paul A.; Bellini, William J.

    2016-01-01

    In the United States, approximately 9% of the measles cases reported from 2012 to 2014 occurred in vaccinated individuals. Laboratory confirmation of measles in vaccinated individuals is challenging since IgM assays can give inconclusive results. Although a positive reverse transcription (RT)-PCR assay result from an appropriately timed specimen can provide confirmation, negative results may not rule out a highly suspicious case. Detection of high-avidity measles IgG in serum samples provides laboratory evidence of a past immunologic response to measles from natural infection or immunization. High concentrations of measles neutralizing antibody have been observed by plaque reduction neutralization (PRN) assays among confirmed measles cases with high-avidity IgG, referred to here as reinfection cases (RICs). In this study, we evaluated the utility of measuring levels of measles neutralizing antibody to distinguish RICs from noncases by receiver operating characteristic curve analysis. Single and paired serum samples with high-avidity measles IgG from suspected measles cases submitted to the CDC for routine surveillance were used for the analysis. The RICs were confirmed by a 4-fold rise in PRN titer or by RT-quantitative PCR (RT-qPCR) assay, while the noncases were negative by both assays. Discrimination accuracy was high with serum samples collected ≥3 days after rash onset (area under the curve, 0.953; 95% confidence interval [CI], 0.854 to 0.993). Measles neutralizing antibody concentrations of ≥40,000 mIU/ml identified RICs with 90% sensitivity (95% CI, 74 to 98%) and 100% specificity (95% CI, 82 to 100%). Therefore, when serological or RT-qPCR results are unavailable or inconclusive, suspected measles cases with high-avidity measles IgG can be confirmed as RICs by measles neutralizing antibody concentrations of ≥40,000 mIU/ml. PMID:27335386

  16. Evaluation of an antibody avidity index method for detecting recent human immunodeficiency virus type 1 infection using an automated chemiluminescence immunoassay.

    Science.gov (United States)

    Fernández, Gema; Manzardo, Christian; Montoliu, Alexandra; Campbell, Colin; Fernández, Gregorio; Casabona, Jordi; Miró, José Maria; Matas, Lurdes; Rivaya, Belén; González, Victoria

    2015-04-01

    Recent infection testing algorithms (RITAs) are used in public health surveillance to estimate the incidence of recently acquired HIV-1 infection. Our aims were (i) to evaluate the precision of the VITROS® Anti-HIV 1+2 automated antibody avidity assay for qualitative detection of antibodies to HIV 1+2 virus; (ii) to validate the accuracy of an automated guanidine-based antibody avidity assay to discriminate between recent and long standing infections using the VITROS 3600 platform; (iii) to compare this method with BED-CEIA assay; and (iv) to evaluate the occurrence of false recent misclassifications by the VITROS antibody avidity assay in patients with a CD4 count de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  17. Immune response to pneumococcal polysaccharides 4 and 14 in elderly and young adults. I Antibody concentrations, avidity and functional activity

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    Carlone George M

    2005-06-01

    Full Text Available Abstract Streptococcus pneumoniae is a serious worldwide pathogen and the focus of numerous vaccine development projects. Currently the most widely accepted surrogate marker for evaluating the efficacy of a given vaccine is to utilize ELISA. Measurement of antibody concentration by ELISA without reduction in cross-reactive antibodies causes an overestimation of antibody concentration and therefore protection, this is most notable in the aged, an at risk group for this infection. We compared the immune response to the pneumococcal polysaccharides (PPS 4 and 14 of 20 young to 20 elderly adults. Pre-and post-vaccination IgG antibody concentrations and antibody avidity against PPS4 and PPS14 were measured using two different enzyme-linked immunosorbant assay (ELISA absorption protocols. All sera were pre-absorbed with either cell-wall polysaccharide (CPS, or CPS and serotype 22F polysaccharide. Pre- and post-vaccination IgG antibody concentrations for serotype 4, but not 14, were significantly lowered with the additional absorption with serotype 22F polysaccharide in both age groups. Young and elderly demonstrated a significant increase from pre- to post-immunization antibody concentration, using either absorption method; and opsonophagocytic antibody titers in response to both PPS4 and PPS14. The correlation coefficients between ELISA and opsonophagocytic assays were improved by additional absorption with serotype 22F in response to serotype 4, but not serotype 14 in all age groups. Opsonophagocytic antibody titers in a sub-group of elderly (>77 years of age were significantly lower than the opsonophagocytic antibody concentrations in young adults. These results suggest the importance of eliminating cross-reactive antibodies from ELISA measurements by absorption of serum and an age-related impairment in the antibody response to pneumococcal polysaccharides.

  18. Generation of polyclonal antibody with high avidity to rosuvastatin and its use in development of highly sensitive ELISA for determination of rosuvastatin in plasma

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    Al-Malaq Hamoud A

    2011-07-01

    Full Text Available Abstract In this study, a polyclonal antibody with high avidity and specificity to the potent hypocholesterolaemic agent rosuvastatin (ROS has been prepared and used in the development of highly sensitive enzyme-linked immunosorbent assay (ELISA for determination of ROS in plasma. ROS was coupled to keyhole limpt hemocyanin (KLH and bovine serum albumin (BSA using carbodiimide reagent. ROS-KLH conjugate was used for immunization of female 8-weeks old New Zealand white rabbits. The immune response of the rabbits was monitored by direct ELISA using ROS-BSA immobilized onto microwell plates as a solid phase. The rabbit that showed the highest antibody titer and avidity to ROS was scarified and its sera were collected. The IgG fraction was isolated and purified by avidity chromatography on protein A column. The purified antibody showed high avidity to ROS; IC50 = 0.4 ng/ml. The specificity of the antibody for ROS was evaluated by indirect ELISA using various competitors from the ROS-structural analogues and the therapeutic agents used with ROS in a combination therapy. The proposed ELISA involved a competitive binding reaction between ROS, in plasma sample, and the immobilized ROS-BSA for the binding sites on a limited amount of the anti-ROS antibody. The bound anti-ROS antibody was quantified with horseradish peroxidase-labeled second anti-rabbit IgG antibody (HRP-IgG and 3,3',5,5'-tetramethylbenzidine (TMB as a substrate for the peroxidase enzyme. The concentration of ROS in the sample was quantified by its ability to inhibit the binding of the anti-ROS antibody to the immobilized ROS-BSA and subsequently the color intensity in the assay wells. The assay enabled the determination of ROS in plasma at concentrations as low as 40 pg/ml.

  19. Performance Evaluation of the VIDAS® Measles IgG Assay and Its Diagnostic Value for Measuring IgG Antibody Avidity in Measles Virus Infection

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    Dina, Julia; Creveuil, Christian; Gouarin, Stephanie; Viron, Florent; Hebert, Amelie; Freymuth, Francois; Vabret, Astrid

    2016-01-01

    The objective of this study is primarily to compare the performance of the VIDAS® Measles immunoglobulin (Ig)G assay to that of two other serological assays using an immunoassay technique, Enzygnost® Anti-measles Virus/IgG (Siemens) and Measles IgG CAPTURE EIA® (Microimmune). The sensitivity and the agreement of the VIDAS® Measles IgG assay compared to the Enzygnost® Anti-measles Virus/IgG assay and the Measles IgG CAPTURE EIA® assay are 100%, 97.2% and 99.0%, 98.4%, respectively. The very low number of negative sera for IgG antibodies does not allow calculation of specificity. As a secondary objective, we have evaluated the ability of the VIDAS® Measles IgG assay to measure anti-measles virus IgG antibody avidity with the help of the VIDAS® CMV IgG Avidity reagent, using 76 sera from subjects with measles and 238 other sera. Different groups of populations were analyzed. In the primary infection measles group, the mean IgG avidity index was 0.16 (range of 0.07 to 0.93) compared to 0.79 (range of 0.25 to 1) in the serum group positive for IgG antibodies and negative for IgM. These data allow to define a weak anti-measles virus IgG antibody avidity as an avidity index (AI) 0.6. The VIDAS® Measles IgG assay has a performance equivalent to that of other available products. Its use, individual and quick, is well adapted to testing for anti-measles immunity in exposed subjects. PMID:27556477

  20. The elicitin-like glycoprotein, ELI025, is secreted by the pathogenic oomycete Pythium insidiosum and evades host antibody responses.

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    Tassanee Lerksuthirat

    Full Text Available Pythium insidiosum is a unique oomycete that can infect humans and animals. Patients with a P. insidiosum infection (pythiosis have high rates of morbidity and mortality. The pathogen resists conventional antifungal drugs. Information on the biology and pathogenesis of P. insidiosum is limited. Many pathogens secrete proteins, known as effectors, which can affect the host response and promote the infection process. Elicitins are secretory proteins and are found only in the oomycetes, primarily in Phytophthora and Pythium species. In plant-pathogenic oomycetes, elicitins function as pathogen-associated molecular pattern molecules, sterol carriers, and plant defense stimulators. Recently, we reported a number of elicitin-encoding genes from the P. insidiosum transcriptome. The function of elicitins during human infections is unknown. One of the P. insidiosum elicitin-encoding genes, ELI025, is highly expressed and up-regulated at body temperature. This study aims to characterize the biochemical, immunological, and genetic properties of the elicitin protein, ELI025. A 12.4-kDa recombinant ELI025 protein (rELI025 was expressed in Escherichia coli. Rabbit anti-rELI025 antibodies reacted strongly with the native ELI025 in P. insidiosum's culture medium. The detected ELI025 had two isoforms: glycosylated and non-glycosylated. ELI025 was not immunoreactive with sera from pythiosis patients. The region near the transcriptional start site of ELI025 contained conserved oomycete core promoter elements. In conclusion, ELI025 is a small, abundant, secreted glycoprotein that evades host antibody responses. ELI025 is a promising candidate for development of diagnostic and therapeutic targets for pythiosis.

  1. High avidity antibodies to full-length VAR2CSA correlate with absence of placental malaria

    DEFF Research Database (Denmark)

    Tutterrow, Yeung Lo; Salanti, Ali; Avril, Marion

    2012-01-01

    VAR2CSA mediates sequestration of Plasmodium falciparum-infected erythrocytes in the placenta, increasing the risk of poor pregnancy outcomes. Naturally acquired antibodies (Ab) to placental parasites at delivery have been associated with improved pregnancy outcomes, but Ab levels and how early...... in pregnancy Ab must be present in order to eliminate placental parasites before delivery remains unknown. Antibodies to individual Duffy-binding like domains of VAR2CSA have been studied, but the domains lack many of the conformational epitopes present in full-length VAR2CSA (FV2). Thus, the purpose...... of this study was to describe the acquisition of Ab to FV2 in women residing in high and low transmission areas and determine how Ab levels during pregnancy correlate with clearance of placental parasites. Plasma samples collected monthly throughout pregnancy from pregnant women living in high and low...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  4. Label-free Fab and Fc affinity/avidity profiling of the antibody complex half-life for polyclonal and monoclonal efficacy screening.

    Science.gov (United States)

    Read, Thomas; Olkhov, Rouslan V; Williamson, E Diane; Shaw, Andrew M

    2015-09-01

    A unified approach to affinity screening for Fab and Fc interactions of an antibody for its antigen and FcγR receptor has been developed. An antigen array is used for the Fab affinity and cross-reactivity screening and protein A/G proxy is the FcγR receptor. The affinities are derived using a simple 1:1 binding model with a consistent error analysis. The association and dissociation kinetics are measured over optimised times for accurate determination. The Fab/Fc affinities are derived for ten antibodies: mAb-actin (mouse), pAb-BSA (sheep), pAb-collagen V (rabbit), pAb-CRP (goat), mAb-F1 (mouse), mAbs (mouse) 7.3, 12.3, 29.3, 36.3 and 46.3 raised against LcrV in Yersinia pestis. The rate of the dissociation of antigen-antibody complexes relates directly to their immunological function as does the Fc-FcγR complex and a new half-life plot has been defined with a Fab/Fc half-life range of 17-470 min. The upper half-life value points to surface avidity. Two antibodies that are protective as an immunotherapy define a Fab half-life >250 min and an Fc half-life >50 min as characteristics of ideal interactions which can form the basis of an antibody screen for immunotherapy.

  5. Juxtamembrane shedding of Plasmodium falciparum AMA1 is sequence independent and essential, and helps evade invasion-inhibitory antibodies.

    Directory of Open Access Journals (Sweden)

    Anna Olivieri

    2011-12-01

    Full Text Available The malarial life cycle involves repeated rounds of intraerythrocytic replication interspersed by host cell rupture which releases merozoites that rapidly invade fresh erythrocytes. Apical membrane antigen-1 (AMA1 is a merozoite protein that plays a critical role in invasion. Antibodies against AMA1 prevent invasion and can protect against malaria in vivo, so AMA1 is of interest as a malaria vaccine candidate. AMA1 is efficiently shed from the invading parasite surface, predominantly through juxtamembrane cleavage by a membrane-bound protease called SUB2, but also by limited intramembrane cleavage. We have investigated the structural requirements for shedding of Plasmodium falciparum AMA1 (PfAMA1, and the consequences of its inhibition. Mutagenesis of the intramembrane cleavage site by targeted homologous recombination abolished intramembrane cleavage with no effect on parasite viability in vitro. Examination of PfSUB2-mediated shedding of episomally-expressed PfAMA1 revealed that the position of cleavage is determined primarily by its distance from the parasite membrane. Certain mutations at the PfSUB2 cleavage site block shedding, and parasites expressing these non-cleavable forms of PfAMA1 on a background of expression of the wild type gene invade and replicate normally in vitro. The non-cleavable PfAMA1 is also functional in invasion. However - in contrast to the intramembrane cleavage site - mutations that block PfSUB2-mediated shedding could not be stably introduced into the genomic pfama1 locus, indicating that some shedding of PfAMA1 by PfSUB2 is essential. Remarkably, parasites expressing shedding-resistant forms of PfAMA1 exhibit enhanced sensitivity to antibody-mediated inhibition of invasion. Drugs that inhibit PfSUB2 activity should block parasite replication and may also enhance the efficacy of vaccines based on AMA1 and other merozoite surface proteins.

  6. Antibodies with High Avidity to the gp120 Envelope Protein in Protection from Simian Immunodeficiency Virus SIVmac251 Acquisition in an Immunization Regimen That Mimics the RV-144 Thai Trial

    Science.gov (United States)

    Pegu, Poonam; Vaccari, Monica; Gordon, Shari; Keele, Brandon F.; Doster, Melvin; Guan, Yongjun; Ferrari, Guido; Pal, Ranajit; Ferrari, Maria Grazia; Whitney, Stephen; Hudacik, Lauren; Billings, Erik; Rao, Mangala; Montefiori, David; Tomaras, Georgia; Alam, S. Munir; Fenizia, Claudio; Lifson, Jeffrey D.; Stablein, Donald; Tartaglia, Jim; Michael, Nelson; Kim, Jerome; Venzon, David

    2013-01-01

    The recombinant canarypox vector, ALVAC-HIV, together with human immunodeficiency virus (HIV) gp120 envelope glycoprotein, has protected 31.2% of Thai individuals from HIV acquisition in the RV144 HIV vaccine trial. This outcome was unexpected, given the limited ability of the vaccine components to induce CD8+ T-cell responses or broadly neutralizing antibodies. We vaccinated macaques with an immunization regimen intended to mimic the RV144 trial and exposed them intrarectally to a dose of the simian immunodeficiency virus SIVmac251 that transmits few virus variants, similar to HIV transmission to humans. Vaccination induced anti-envelope antibodies in all vaccinees and CD4+ and CD8+ T-cell responses. Three of the 11 macaques vaccinated with ALVAC-SIV/gp120 were protected from SIVmac251 acquisition, but the result was not significant. The remaining vaccinees were infected and progressed to disease. The magnitudes of vaccine-induced SIVmac251-specific T-cell responses and binding antibodies were not significantly different between protected and infected animals. However, sera from protected animals had higher avidity antibodies to gp120, recognized the variable envelope regions V1/V2, and reduced SIVmac251 infectivity in cells that express high levels of α4β7 integrins, suggesting a functional role of antibodies to V2. The current results emphasize the utility of determining the titer of repeated mucosal challenge in the preclinical evaluation of HIV vaccines. PMID:23175374

  7. Antibodies with high avidity to the gp120 envelope protein in protection from simian immunodeficiency virus SIV(mac251) acquisition in an immunization regimen that mimics the RV-144 Thai trial.

    Science.gov (United States)

    Pegu, Poonam; Vaccari, Monica; Gordon, Shari; Keele, Brandon F; Doster, Melvin; Guan, Yongjun; Ferrari, Guido; Pal, Ranajit; Ferrari, Maria Grazia; Whitney, Stephen; Hudacik, Lauren; Billings, Erik; Rao, Mangala; Montefiori, David; Tomaras, Georgia; Alam, S Munir; Fenizia, Claudio; Lifson, Jeffrey D; Stablein, Donald; Tartaglia, Jim; Michael, Nelson; Kim, Jerome; Venzon, David; Franchini, Genoveffa

    2013-02-01

    The recombinant canarypox vector, ALVAC-HIV, together with human immunodeficiency virus (HIV) gp120 envelope glycoprotein, has protected 31.2% of Thai individuals from HIV acquisition in the RV144 HIV vaccine trial. This outcome was unexpected, given the limited ability of the vaccine components to induce CD8(+) T-cell responses or broadly neutralizing antibodies. We vaccinated macaques with an immunization regimen intended to mimic the RV144 trial and exposed them intrarectally to a dose of the simian immunodeficiency virus SIV(mac251) that transmits few virus variants, similar to HIV transmission to humans. Vaccination induced anti-envelope antibodies in all vaccinees and CD4(+) and CD8(+) T-cell responses. Three of the 11 macaques vaccinated with ALVAC-SIV/gp120 were protected from SIV(mac251) acquisition, but the result was not significant. The remaining vaccinees were infected and progressed to disease. The magnitudes of vaccine-induced SIV(mac251)-specific T-cell responses and binding antibodies were not significantly different between protected and infected animals. However, sera from protected animals had higher avidity antibodies to gp120, recognized the variable envelope regions V1/V2, and reduced SIV(mac251) infectivity in cells that express high levels of α(4)β(7) integrins, suggesting a functional role of antibodies to V2. The current results emphasize the utility of determining the titer of repeated mucosal challenge in the preclinical evaluation of HIV vaccines.

  8. Comparison of immunofluorescence and enzyme-linked immunosorbent assay and immunoglobulin G avidity techniques for screening of anti: Toxoplasma antibodies among single serum sample pregnant women in Tabriz, Iran

    Directory of Open Access Journals (Sweden)

    Mehrangiz Rajaii

    2015-01-01

    Full Text Available Background: Congenital toxoplasmosis is that pregnant women acquire the infection during gestation; diagnosis of the acute infection during pregnancy is a complex subject of maternal toxoplasmosis. Thus, the presence of immunoglobulin G (IgG and/or IgM Toxoplasma antibodies in a single serum sample drawn during gestation cannot be used to define whether the infection was recently acquired or chronic. Materials and Methods: At this cross-sectional descriptive study, sera of 391 pregnant women examined and compared. They were in an age range of 21-35 years, referred by gynecologists and infectious disease specialists, during March 2012-April 2013. They have referred, 215 (54.98%, 102 (26%, 74 (18.92% in the first, second and third trimesters of gestation, respectively. For each of them, a questionnaire was completed and serum samples were prepared in an equal condition, examined according to the procedures of indirect immunofluorescence (IIF, enzyme-linked immunosorbent assay (ELISA and IgG Avidity techniques. Results: We have found 111 (28.38% seronegative and 280 (71.61% seropositive cases by IIF and 124 (31.70% seronegative, 267 (68.28% seropositive cases by ELISA. The IgG avidity test confirmed 45 (69.23% and 7 (10.76% doubtful cases of IgM test in IIF and ELISA techniques. Conclusions: This study highlights how to manage pregnant women with toxoplasmosis, especially in a single serum sample condition.

  9. Immunoglobulin M indirect-fluorescent antibody test for the diagnosis of acute toxoplasmosis during pregnancy in the avidity era: A 14-year experience at the Tuscany Reference Center for Infectious Diseases in Pregnancy, Florence, Italy.

    Science.gov (United States)

    Trotta, Michele; Borchi, Beatrice; Zammarchi, Lorenzo; Sterrantino, Gaetana; Brogi, Michela; Kiros, Seble Tekle; Lorini, Chiara; Bonaccorsi, Guglielmo; Colao, Maria Grazia; Bartoloni, Alessandro

    2016-12-01

    The aim of this study was to evaluate immunoglobulin M indirect-fluorescent antibody test (IgM IFAT) for the diagnosis of acute or chronic Toxoplasma infection in pregnancy. Pregnant women with suspected acute toxoplasmosis referred to the Tuscany Reference Center for Infectious Diseases in Pregnancy during the period 1998-2012 were retrospectively enrolled. All women were tested with a panel of serological tests, including enzyme-linked immunosorbent assay for IgG avidity and IgM IFAT. On the basis of anamnestic, clinical, and serological criteria, pregnant women were classified into three groups: recently infected (RI), latently infected (LI), and doubtful latently infected (DLI). Patients classified as DLI were excluded from the analysis. The association between IgM IFAT (positive or negative) and the diagnosis of infection (acute or chronic) was assessed. Positive predictive value and negative predictive value of the IgM IFAT were calculated. A total of 810 pregnant women were enrolled in the study: 302 in the RI group and 508 in the LI group. Fifty-two women classified as DLI were excluded. IgM IFAT was positive in 172 out of 302 (56.9%) pregnant women in the RI group and in 29 out of 508 (5.7%) in the LI group. The positive predictive value and negative predictive value of IgM IFAT in predicting RI was 85.6% and 78.6%, respectively. IgM IFAT has reasonable sensitivity and specificity in diagnosing recent infection and, mostly in case of borderline avidity test, could be considered as a further aid for an accurate diagnosis of acute toxoplasmosis in pregnancy. © 2016 Japan Society of Obstetrics and Gynecology.

  10. Evader Interdiction and Collateral Damage

    Energy Technology Data Exchange (ETDEWEB)

    Gutfraind, Alexander [Los Alamos National Laboratory

    2011-01-01

    In network interdiction problems, evaders (hostile agents or data packets) are moving through a network towards their targets and we wish to choose sensor placement locations in order to intercept them before they reach their destinations. Sensor locations should be chosen economically, balancing security gains with cost, including the inconvenience sensors inflict upon innocent travelers. We give optimal sensor allocation algorithms for several classes of special graphs and hardness and optimal approximation results for general graphs, including for deterministic or Markov chain-based and oblivious or reactive evaders. In a similar-sounding but much different problem setting posed by [10] where the innocent travelers can also be reactive, we again give optimal algorithms for special cases and hardness and (essentially) optimal approximation results on general graphs.

  11. Serological IgG avidity test for ocular toxoplasmosis

    Directory of Open Access Journals (Sweden)

    Suresh S

    2012-01-01

    Full Text Available Subramaniam Suresh1, Saidin Nor-Masniwati1, Muhd Nor Nor-Idahriani1, Wan-Hitam Wan-Hazabbah1, Mohamed Zeehaida2, Embong Zunaina11Department of Ophthalmology, 2Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, MalaysiaBackground: The purpose of this study was to evaluate the immunoglobulin (Ig G avidity of serological toxoplasmosis testing in patients with ocular inflammation and to determine the clinical manifestations of ocular toxoplasmosis.Methods: A retrospective review of all patients presenting with ocular inflammation to the Hospital Universiti Sains Malaysia, Kelantan, Malaysia between 2005 and 2009 was undertaken. Visual acuity, clinical manifestations at presentation, toxoplasmosis antibody testing, and treatment records were analyzed.Results: A total of 130 patients with ocular inflammation were reviewed retrospectively. The patients had a mean age of 38.41 (standard deviation 19.24, range 6–83 years. Seventy-one patients (54.6% were found to be seropositive, of whom five (3.8% were both IgG and IgM positive (suggestive of recently acquired ocular toxoplasmosis while one (0.8% showed IgG avidity ≤40% (suggestive of recently acquired ocular toxoplasmosis and 65 patients (50.0% showed IgG avidity >40% (suggestive of reactivation of toxoplasmosis infection. Chorioretinal scarring as an ocular manifestation was significantly more common in patients with seropositive toxoplasmosis (P = 0.036. Eighteen patients (13.8% were diagnosed as having recent and/or active ocular toxoplasmosis based on clinical manifestations and serological testing.Conclusion: Ocular toxoplasmosis is a clinical diagnosis, but specific toxoplasmosis antibody testing helps to support the diagnosis and to differentiate between reactivation of infection and recently acquired ocular toxoplasmosis.Keywords: ocular toxoplasmosis, chorioretinal scar, toxoplasmosis antibody, IgG avidity test

  12. Primary cytomegalovirus infection in pregnant Egyptian women confirmed by cytomegalovirus IgG avidity testing.

    Science.gov (United States)

    Kamel, N; Metwally, L; Gomaa, N; Sayed Ahmed, W A; Lotfi, M; Younis, S

    2014-01-01

    To determine the frequency of primary cytomegalovirus (CMV) infection in pregnant Egyptian women using CMV IgG avidity testing. A cross-sectional study was conducted at Suez Canal University Hospital, Ismailia, Egypt. A total of 546 pregnant women, presenting for routine antenatal screening, were tested for CMV IgG and IgM using a commercially available enzyme-linked immunosorbent assay (ELISA). Sera from CMV IgM-positive women were tested by CMV IgG avidity assay. All the 546 pregnant women were seropositive for anti-CMV IgG. Of the 546 women, 40 (7.3%) were positive or equivocal for IgM antibodies. All sera from the 40 women (IgG+/IgM+) showed a high or intermediate CMV IgG avidity index. Of the 40 women, 23 (57.5%) were in the second or third trimesters of pregnancy and had their first-trimester blood retrieved, and the tested CMV IgG avidity assay showed a high avidity index. Women who were IgM positive had no primary CMV infection in the index pregnancy as evidenced by the high CMV IgG avidity testing. © 2013 S. Karger AG, Basel.

  13. Serodiagnosis of Toxoplasmosis: The effect of measurement of IgG avidity in pregnant women in Rabat in Morocco.

    Science.gov (United States)

    Laboudi, Majda; Sadak, Abderrahim

    2017-08-01

    The diagnosis of Toxoplasmosis in pregnant women during the early first trimester of pregnancy is very important for preventing congenital infection of the fetus; it will not only prevent the risk of transmitting the infection to the fetus but it will also enable to give these women a preventive treatment. In this study, the avidity test was performed on pregnant women during their first prenatal visit at the National Institute of Hygiene in Rabat, Morocco. One hundred and twenty-eight sera samples were collected from 128 pregnant women between August 2015 and June 2016; these women were chosen retrospectively and were in their first four months of pregnancy. The samples were screened using the specific anti-Toxoplasma IgG and IgM antibodies and were subjected to an IgG avidity test. After the serological screening, only 54 women (42.4%) were tested positive for IgG antibodies and five women (3.9%) were tested positive for both anti-Toxoplasma IgG and IgM antibodies. Four IgM-negative women had low-avidity antibodies. However, none of the IgG-avidity test had detected low-avidity antibodies in the five IgM-positive women; three women (60%) had high-avidity antibodies, indicating that the infection was acquired in the distant past. The avidity test is a helpful tool to exclude a recently acquired toxoplasmosis infection within IgM-positive serum samples in pregnant women during their first trimester of pregnancy. Thus, allowing to perform an appropriate therapeutic intervention. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Partnering with AVID to create transportation scholars

    Science.gov (United States)

    2010-10-01

    The goal of this project was to team with the Advancement Via Individual Determination (AVID) : program in local schools to stimulate student awareness of transportation and engineering careers and to : encourage interest in the science, technology, ...

  15. High Avidity dsDNA Autoantibodies in Brazilian Women with Systemic Lupus Erythematosus: Correlation with Active Disease and Renal Dysfunction

    Directory of Open Access Journals (Sweden)

    Rodrigo C. Oliveira

    2015-01-01

    Full Text Available We investigated in Brazilian women with SLE the prevalence and levels of high avidity (HA dsDNA antibodies and tested their correlation with lupus activity and biomarkers of renal disease. We also compared these correlations to those observed with total dsDNA antibodies and antibodies against nucleosome (ANuA. Autoantibodies were detected by ELISA, while C3 and C4 levels were determined by nephelometry. Urine protein/creatinine ratio was determined, and lupus activity was measured by SLEDAI-2K. The prevalence of total and HA dsDNA antibodies was similar to but lower than that verified for ANuA. The levels of the three types of antibodies were correlated, but the correlation was more significant between HA dsDNA antibodies and ANuA. High avidity dsDNA antibodies correlated positively with ESR and SLEDAI and inversely with C3 and C4. Similar correlations were observed for ANuA levels, whereas total dsDNA antibodies only correlated with SLEDAI and C3. The levels of HA dsDNA antibodies were higher in patients with proteinuria, but their levels of total dsDNA antibodies and ANuA were unaltered. High avidity dsDNA antibodies can be found in high prevalence in Brazilian women with SLE and are important biomarkers of active disease and kidney dysfunction.

  16. Persistent Low Toxoplasma IgG Avidity Is Common in Pregnancy: Experience from Antenatal Testing in Norway.

    Directory of Open Access Journals (Sweden)

    Gry Findal

    Full Text Available The parasite Toxoplasma gondii might harm the fetus if a woman is infected during pregnancy. IgG seroconversion and significant increase in IgG antibody amount in pregnancy indicates maternal infection. Presence of toxoplasma immunoglobulin M (IgM, immunoglobulin G (IgG and low IgG avidity in a single serum sample indicates possible maternal infection, but positive toxoplasma IgM and low IgG avidity may persist for months and even years. We aimed to evaluate avidity development during pregnancy in a retrospective study. Serial blood samples from 176 pregnant women admitted to Oslo University Hospital 1993-2013 for amniocentesis because of suspected toxoplasma infection were included. Data were obtained from journals and laboratory records. The avidity method used was based on Platelia Toxo IgG assay. Mean maternal age at first serology was 29.9 years (SD 5.2, range 18-42. In 37 (21% women only the avidity increased from low to high in < 3 months. In 139 (79% the IgG avidity remained below the high threshold ≥ 3 months and within this group 74 (42% women had stable low IgG avidity during the observation period. Median gestational age at first test was 10.6 weeks (range 4.6-28.7. Fetal infection was detected in four children, but none among children whose mother had stable low IgG avidity. The first antenatal toxoplasma serology should ideally be collected in early pregnancy and if stable values of toxoplasma IgM and low IgG-avidity are detected in a second sample after three to four weeks, the need for amniocentesis can be questioned.

  17. Direct block scheduling technology: Analysis of Avidity

    Directory of Open Access Journals (Sweden)

    Felipe Ribeiro Souza

    Full Text Available Abstract This study is focused on Direct Block Scheduling testing (Direct Multi-Period Scheduling methodology which schedules mine production considering the correct discount factor of each mining block, resulting in the final pit. Each block is analyzed individually in order to define the best target period. This methodology presents an improvement of the classical methodology derived from Lerchs-Grossmann's initial proposition improved by Whittle. This paper presents the differences between these methodologies, specially focused on the algorithms' avidity. Avidity is classically defined by the voracious search algorithms, whereupon some of the most famous greedy algorithms are Branch and Bound, Brutal Force and Randomized. Strategies based on heuristics can accentuate the voracity of the optimizer system. The applied algorithm use simulated annealing combined with Tabu Search. The most avid algorithm can select the most profitable blocks in early periods, leading to higher present value in the first periods of mine operation. The application of discount factors to blocks on the Lerchs-Grossmann's final pit has an accentuated effect with time, and this effect may make blocks scheduled for the end of the mine life unfeasible, representing a trend to a decrease in reported reserves.

  18. Improved testing of recent HIV-1 infections with the BioRad avidity assay compared to the limiting antigen avidity assay and BED Capture enzyme immunoassay: evaluation using reference sample panels from the German Seroconverter Cohort.

    Directory of Open Access Journals (Sweden)

    Andrea Hauser

    Full Text Available BACKGROUND: The variety and limitations of current laboratory methods for estimating HIV-incidence has driven attempts to improve and standardize the performance of serological 'Tests for Recent HIV-Infections' (TRI. Primary and follow-up HIV-1 positive plasma samples from individuals with well-defined dates of infection collected as part of the German Seroconverter Cohort provided specimens highly suitable for use in comparing the performance of three TRIs: the AWARE™ BED™ EIA HIV-1 Incidence test (BED-CEIA, Genetic systems HIV-1/HIV-2 Plus O EIA antibody avidity-based assay (BioRad Avidity and Sedia™ HIV-1 LAg Avidity EIA (LAg Avidity. METHODS: The evaluation panel included 180 specimens: 44 from antiretroviral (ARV-naïve individuals with recently acquired HIV-infection (≤ 130 days; 25 B and 19 non-B subtypes and 136 from long-term (>12 months infected individuals [101 ARV-naïve subtype B, 16 non-B subtypes, 14 ARV-treated individuals, 5 slow progressors (SLP]. RESULTS: For long-term infected, ARV-naïve individuals the false recent rates (FRR of both the BioRad and LAg Avidity assays were 2% (2/101 for subtype B and 6% (1/16 for subtype 'non-B', while the FRR of the BED-CEIA was 7% (7/101 for subtype B and 25% (4/16 for subtype 'non-B' (all p>0.05. Misclassification of ARV-treated individuals and SLP was rare by LAg (1/14, 0/5 and BioRad Avidity assays (2/14, 1/5 but more frequent by BED-CEIA (5/14, 3/5. Among recently-infected individuals (subtype B, 60% (15/25 were correctly classified by BED-CEIA, 88% (22/25 by BioRad Avidity and significantly fewer by LAg (48%, 12/25 compared to BioRad Avidity (p = 0.005 with a higher true-recency rate among non-B infections for all assays. CONCLUSIONS: This study using well-characterized specimens demonstrated lower FRRs for both avidity methods than with the BED-CEIA. For recently infected individuals the BioRad Avidity assay was shown to give the most accurate results.

  19. Optimal interdiction of unreactive Markovian evaders

    Energy Technology Data Exchange (ETDEWEB)

    Gutfraind, Alexander [Los Alamos National Laboratory; Hagberg, Aric [Los Alamos National Laboratory; Pan, Feng [Los Alamos National Laboratory

    2008-01-01

    The network interdiction problem arises in a wide variety of areas including military logistics, infectious disease control and counter-terrorism. In the classical formulation one is given a weighted network G(N, E) and the task is to find b nodes (or edges) whose removal would maximally increase the least-cost path from a source node s to a target node r. In practical applications. G represenLs a transportation or activity network; node/edge removal is done by an agent, the 'interdictor' against another agent the 'evader' who wants to traverse G from s to t along the least-cost route. Our work is motivated by cases in which both agents have bounded rationality: e.g. when the authorities set up road blocks to catch bank robbers, neither party can plot its actions with full information about the other. We introduce a novel model of network interdiction in which the motion of (possibly) several evaders i. described by a Markov pr cess on G.We further suppose that the evaden; do not respond to interdiction decisions because of time, knowledge or computational constraint . We prove that this interdiction problem is NP-hard, like the classical formulation, but unlike the classical problem the objective function is submodular. This implies that the solution could be approximated within 1-lie using a greedy algorithm. Exploiting submodularity again. we demonstrate that a 'priority' (or 'lazy') evaluation algorithm can improve performance by orders of magnitude. Taken together, the results bring closer realistic solutions to the interdiction problem on global-scale networks.

  20. Diagnosis of acute toxoplasmosis in pregnant women referred to therapeutic centers of Alborz Province (Iran using immunoglobulin G avidity ELISA technique

    Directory of Open Access Journals (Sweden)

    Lame Akhlaghi

    2016-11-01

    Full Text Available Objective: To evaluate immunoglobulin G (IgG avidity as a useful and reliable technique in diagnosing toxoplasmosis in pregnant women referring to therapeutic centers of Alborz Province (Iran in 2014, against two other tests, IgG and immunoglobulin G (IgM antiToxoplasma. Methods: Serum samples (468 in total were obtained from different therapeutic centers in Karaj City. ELISA method was used to test the anti-Toxoplasma avidity of IgG, IgM and IgG. The data were analyzed by descriptive statistical methods and Chi-square test (P < 0.05 using SPSS 17.0. Results: Anti-Toxoplasma tests of IgM and IgG were positive in 9 and 86 samples respectively. Also, a borderline IgM was detected in 2 suspected samples. In addition, among all positive and suspected samples, 79 cases indicated high titers of IgG avidity, 7 cases were of low titers and 1 case was of a borderline titer. The prevalence of anti-Toxoplasma antibodies was 20%. The sera which showed high avidity index was obtained from patients at chronic phase of infection (92% while those which showed low avidity levels were from patients at acute toxoplasmosis (77.7%. Conclusions: This study clearly showed that acute and chronic phases of toxoplasmosis could be differentiated with the aid of IgG avidity test. This test may also assist in recognizing old and newly acquired infections.

  1. Antibody Maturation in Trypanosoma cruzi-Infected Rats

    Science.gov (United States)

    Marcipar, Iván S.; Risso, Marikena G.; Silber, Ariel M.; Revelli, Silvia; Marcipar, Alberto J.

    2001-01-01

    The study of antibody avidity changes during infection has improved the understanding of the pathologic processes involved in several infectious diseases. In some infections, like toxoplasmosis, this information is being used for diagnostic purposes. Results of the evolution of antibody avidity for different specific antigens in Trypanosome cruzi-infected rats are presented. A Western blotting technique, combined with avidity analysis to identify antigens that elicit high-avidity antibodies, is suggested. In this system, antibodies showed high avidity values only during the chronic phase of infection and only in relation to antibodies against 21-, 33-, 41-, 42-, 56-, 58-, 66-, and 72-kDa antigens. Finally, a 97-kDa T. cruzi antigen, which was recognized by high-avidity antibodies and occurred in noninfected rats, was identified. These results allow us to evaluate the different antigens in chagasic infection. Our results show that with the correct choice of antigen it is possible to detect differences in maturation of antibodies and to discriminate, in an experimental model, between recent (acute) and chronic infections. PMID:11427430

  2. Inflammatory pseudotumor: A gallium-avid mobile mesenteric mass

    International Nuclear Information System (INIS)

    Auringer, S.T.; Scott, M.D.; Sumner, T.E.

    1991-01-01

    An 8-yr-old boy with a 1-mo history of culture-negative fever and anemia underwent gallium, ultrasound, and computed tomography studies as part of the evaluation of a fever of unknown origin. These studies revealed a mobile gallium-avid solid abdominal mass subsequently proven to be an inflammatory pseudotumor of the mesentery, a rare benign mass. This report documents the gallium-avid nature of this rare lesion and discusses associated characteristic clinical, pathologic, and radiographic features

  3. Antibodies to phosphatidylserine/prothrombin complex as an additional diagnostic marker of APS?

    Science.gov (United States)

    Žigon, P; Čučnik, S; Ambrožič, A; Sodin Šemrl, S; Kveder, T; Božič, B

    2012-06-01

    Antiprothrombin antibodies can be measured by ELISA using either a prothrombin/phosphatidylserine complex (aPS/PT) or prothrombin alone (aPT) as antigen. We aimed to compare the clinical features of autoimmune patients with avidity of aPS/PT and determine the diagnostic efficiency of aPS/PT and aPT for assessing antiphospholipid syndrome (APS). aPS/PT were of low (n = 9), heterogeneous (n = 31) and high (n = 8) avidity out of 48 cases. None of the samples with low avidity were positive in aPT ELISA. Among patients with heterogeneous or high avidity aPS/PT, there was a significantly greater number of patients with APS as compared to patients with low avidity (38/39 vs. 7/9; p < 0.05). No SLE patients had high avidity antiprothrombin antibodies.

  4. Ultrasound stratification of the FDG-avid thyroid nodule

    International Nuclear Information System (INIS)

    Beech, P.; Lavender, I.; Jong, I.; Soo, G.; Ramdave, S.; Chong, A.; Nandurkar, D.

    2016-01-01

    Aim: To determine whether the malignancy risk in an 2-["1"8F]-fluoro-2-deoxy-D-glucose (FDG)-avid thyroid nodule can be stratified according to the presence or absence of suspicious ultrasound features and thereby identify which nodules require further cytological assessment. Materials and methods: A retrospective review of FDG-positron-emission tomography (PET) combined with computed tomography (CT) studies with FDG-avid thyroid nodules (defined as FDG uptake greater than blood pool) that were further assessed with ultrasound and fine-needle aspiration cytology or surgery was performed. FDG-avid thyroid nodules were classified as having either suspicious ultrasound features (marked hypo-echogenicity, irregular margins, microcalcifications, marked hypervascularity, or nodules that were taller than they were wide) or no suspicious ultrasound features and these findings were correlated with the subsequent cytological results. Results: Forty-eight FDG-avid thyroid nodules were assessed. On cytological assessment five nodules were malignant (10.4%), nine were indeterminate (18.75%), and 34 were benign (70.8%). On ultrasound, 24 (50%) had no suspicious features and 24 (50%) had one or more suspicious features. Of the nodules with no suspicious features, 22 (91.6%) were benign, two (8.3%) were indeterminate, and none were malignant. Of the nodules with suspicious features, five (20.8%) were malignant, seven (29.1%) were indeterminate, and 12 (50%) were benign. The absence of suspicious ultrasound features demonstrated a strong association with benign cytology (p=0.009). Out of the suspicious sonographic features, marked hypoechoic appearance (p=0.02), irregular margins (p=0.009), and taller than wide morphology (p=0.04) were statistically most significantly associated with malignancy. Conclusion: The rate of malignancy in FDG-avid thyroid nodules is low in the absence of specific suspicious ultrasound features. The SUV values are non-discriminatory to differentiate

  5. Quantum Backaction Evading Measurement of Collective Mechanical Modes.

    Science.gov (United States)

    Ockeloen-Korppi, C F; Damskägg, E; Pirkkalainen, J-M; Clerk, A A; Woolley, M J; Sillanpää, M A

    2016-09-30

    The standard quantum limit constrains the precision of an oscillator position measurement. It arises from a balance between the imprecision and the quantum backaction of the measurement. However, a measurement of only a single quadrature of the oscillator can evade the backaction and be made with arbitrary precision. Here we demonstrate quantum backaction evading measurements of a collective quadrature of two mechanical oscillators, both coupled to a common microwave cavity. The work allows for quantum state tomography of two mechanical oscillators, and provides a foundation for macroscopic mechanical entanglement and force sensing beyond conventional quantum limits.

  6. Comparison of Toxoplasma gondii IgG avidity Architect and Vidas assays with the estimated date of infection in pregnant women

    Directory of Open Access Journals (Sweden)

    Smets Aurélie

    2016-01-01

    Full Text Available A maternal Toxoplasma gondii infection during pregnancy is a risk for congenital infection through maternal-fetal transplacental transmission. Estimation of the date of infection is of the utmost importance for management and treatment recommendations. In this setting, IgG avidity has been shown to be useful as high avidity rules out an infection dating less than 4 months. The estimated date of infection can also be obtained by the ratio of T. gondii IgG titers measured by the Vidas (bioMérieux assay versus T. gondii IgG titers measured by the Architect (Abbott Laboratories test, together with T. gondii IgM and IgA antibody responses. In this study, using 117 serum samples from pregnant women, we compared the IgG avidity values obtained by Architect and Vidas with the presumed date of T. gondii infection established by the T. gondii IgG ratio of IgG Vidas and IgG Architect plus the IgM and IgA results. To date, IgG avidity Vidas seems to exhibit better performance than Architect. For both assays, gray zone results were most likely obtained from patients infected more than 4 months before sampling. These data should be taken into account for a possible reconsideration of the interpretation of avidity results in the gray zone.

  7. Testing the ability of viral haemorrhagic septicaemia virus to evade the protective immune response induced in rainbow trout by DNA vaccination

    DEFF Research Database (Denmark)

    Sepulveda, Dagoberto; Lorenzen, Niels

    2013-01-01

    , this work aims to evaluate whether VHSV is able to evade the protective immune response induced by the DNA vaccination. Earlier studies have demonstrated that VHSV can evade the neutralizing effect of monoclonal antibodies by mutations in the glycoprotein gene. One approach of the present study is therefore...... to try to isolate VHSV variants which can escape the neutralizing activity of serum from fish immunized with the DNA vaccine. To do so, a highly pathogenic VHSV isolate (DK3592B) will be repeatedly passaged in fish cell cultures in the presence of neutralizing fish serum. Another approach comprises...

  8. Täna algavad Eesti Muusika Päevad

    Index Scriptorium Estoniae

    2004-01-01

    Eesti Muusika Päevade raames toimunud üritustest 21. aprillini: ERSO sümfooniakontserdist Estonia kontserdisaalis, Jüri Reinvere radiofoonilise ooperi "Vastaskallas" esiettekandest Tallinna Linnateatri Hobuveski saalis, kontserdist Kunstihoone Vabaduse väljakul (esitusel Urmas Sisaski uus "Tähistaeva tsükkel" - "Eesti rahvataevas"), lastekontserdist "Kodumaine viis" Estonia kontserdisaalis

  9. Ooperipäevad Saaremaal (II) / Tiiu Levald

    Index Scriptorium Estoniae

    Levald, Tiiu, 1940-

    2008-01-01

    21.-27. VII Saaremaa ooperipäevade raames toimunud üritustest - Carmen Tabori lavastatud Aino Kallase ja Tauno Pylkkäneni "Patseba Saaremaal" (esimene osa draama- ja teine ooperilavastus), Gershwini ooperist "Porgy ja Bess" ning 25. VII toimunud galakontserdist

  10. The Role of Leaders in AVID Schools and the Impact on Student Achievement

    OpenAIRE

    Noone, Colleen Callahan

    2010-01-01

    The Advancement Via Individual Determination (AVID) program is designed to provide resources and strategies to enable underrepresented minority students to attend four-year colleges. Research indicates that the success of the students enrolled in AVID depends on the strict adherence to the AVID components. The purpose of this study was to determine whether the principal and administratorâ s understanding of, commitment to and involvement in AVID accounted for the difference in student achi...

  11. Accuracy of different thresholds for the anti-HIV avidity index

    Directory of Open Access Journals (Sweden)

    Claudio Galli

    2008-03-01

    Full Text Available Surveillance programs for human immunodeficiency virus (HIV infection are based on the reporting of newly diagnosed cases. In order to guarantee a more accurate estimate of the trends and behaviours of infected people, simple and reliable methods aimed at identifying recent (< 6 months HIV infections are needed. We evaluated the accuracy of the avidity index (AI of anti-HIV antibodies on 357 serum samples obtained from 127 subjects for whom an estimated date of seroconversion was calculated on the basis of the interval between the last negative and first positive anti-HIV test result.The ROC curve analysis performed at different thresholds of the AI showed that a cutoff of 0.80 (93.0% sensitivity and 98.5% specificity yields the best overall accuracy (95.8% and should be employed for surveillance purposes, whereas the application of the anti-HIV AI on individual cases is not recommended.

  12. Antithyroglobulin antibody

    Science.gov (United States)

    Thyroglobulin antibody; Thyroiditis - thyroglobulin antibody; Hypothyroidism - thyroglobulin antibody; Thyroiditis - thyroglobulin antibody; Graves disease - thyroglobulin antibody; Underactive thyroid - thyroglobulin antibody

  13. IL-4 and IL-13 mediated down-regulation of CD8 expression levels can dampen anti-viral CD8⁺ T cell avidity following HIV-1 recombinant pox viral vaccination.

    Science.gov (United States)

    Wijesundara, Danushka K; Jackson, Ronald J; Tscharke, David C; Ranasinghe, Charani

    2013-09-23

    We have shown that mucosal HIV-1 recombinant pox viral vaccination can induce high, avidity HIV-specific CD8(+) T cells with reduced interleukin (IL)-4 and IL-13 expression compared to, systemic vaccine delivery. In the current study how these cytokines act to regulate anti-viral CD8(+) T, cell avidity following HIV-1 recombinant pox viral prime-boost vaccination was investigated. Out of a panel of T cell avidity markers tested, only CD8 expression levels were found to be enhanced on, KdGag197-205 (HIV)-specific CD8(+) T cells obtained from IL-13(-/-), IL-4(-/-) and signal transducer and, activator of transcription of 6 (STAT6)(-/-) mice compared to wild-type (WT) controls following, vaccination. Elevated CD8 expression levels in this instance also correlated with polyfunctionality, (interferon (IFN)-γ, tumour necorsis factor (TNF)-α and IL-2 production) and the avidity of HIVspecific CD8(+) T cells. Furthermore, mucosal vaccination and vaccination with the novel adjuvanted IL-13 inhibitor (i.e. IL-13Rα2) vaccines significantly enhanced CD8 expression levels on HIV-specific CD8(+), T cells, which correlated with avidity. Using anti-CD8 antibodies that blocked CD8 availability on CD8(+), T cells, it was established that CD8 played an important role in increasing HIV-specific CD8(+) T cell avidity and polyfunctionality in IL-4(-/-), IL-13(-/-) and STAT6(-/-) mice compared to WT controls, following vaccination. Collectively, our data demonstrate that IL-4 and IL-13 dampen CD8 expression levels on anti-viral CD8(+) T cells, which can down-regulate anti-viral CD8(+) T cell avidity and, polyfunctionality following HIV-1 recombinant pox viral vaccination. These findings can be exploited to, design more efficacious vaccines not only against HIV-1, but many chronic infections where high, avidity CD8(+) T cells help protection. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. AVID: An integrative framework for discovering functional relationships among proteins

    Directory of Open Access Journals (Sweden)

    Keating Amy E

    2005-06-01

    Full Text Available Abstract Background Determining the functions of uncharacterized proteins is one of the most pressing problems in the post-genomic era. Large scale protein-protein interaction assays, global mRNA expression analyses and systematic protein localization studies provide experimental information that can be used for this purpose. The data from such experiments contain many false positives and false negatives, but can be processed using computational methods to provide reliable information about protein-protein relationships and protein function. An outstanding and important goal is to predict detailed functional annotation for all uncharacterized proteins that is reliable enough to effectively guide experiments. Results We present AVID, a computational method that uses a multi-stage learning framework to integrate experimental results with sequence information, generating networks reflecting functional similarities among proteins. We illustrate use of the networks by making predictions of detailed Gene Ontology (GO annotations in three categories: molecular function, biological process, and cellular component. Applied to the yeast Saccharomyces cerevisiae, AVID provides 37,451 pair-wise functional linkages between 4,191 proteins. These relationships are ~65–78% accurate, as assessed by cross-validation testing. Assignments of highly detailed functional descriptors to proteins, based on the networks, are estimated to be ~67% accurate for GO categories describing molecular function and cellular component and ~52% accurate for terms describing biological process. The predictions cover 1,490 proteins with no previous annotation in GO and also assign more detailed functions to many proteins annotated only with less descriptive terms. Predictions made by AVID are largely distinct from those made by other methods. Out of 37,451 predicted pair-wise relationships, the greatest number shared in common with another method is 3,413. Conclusion AVID provides

  15. Bacteriophages use hypermodified nucleosides to evade host's defence systems

    DEFF Research Database (Denmark)

    Kot, Witold; Olsen, Nikoline S.; Carstens, Alexander Byth

    developed several strategies to evade these defence mechanisms. Ultimately, this led to the oldest and still running arms race - microorganisms vs. their molecular parasites. We here describe a remarkable new strategy used by the recently isolated Escherichia coli phage CAjan belonging to...... to investigate this mechanism in detail we have used several methods including direct plaque sequencing, restriction endonuclease analysis and CRISPR-Cas genome editing. Through generation of specific mutants, we were able to introduce a restriction sensitive phenotype in the CAjan bacteriophage providing new...

  16. Evading Lyth bound in models of quintessential inflation

    International Nuclear Information System (INIS)

    Hossain, Md. Wali; Myrzakulov, R.; Sami, M.; Saridakis, Emmanuel N.

    2014-01-01

    Quintessential inflation refers to an attempt to unify inflation and late-time cosmic acceleration using a single scalar field. In this letter we consider two different classes of quintessential inflation, one of which is based upon a Lagrangian with non-canonical kinetic term k 2 (ϕ)∂ μ ϕ∂ μ ϕ and a steep exponential potential while the second class uses the concept of steep brane world inflation. We show that in both cases the Lyth bound can be evaded, despite the large tensor-to-scalar ratio of perturbations. The post-inflationary dynamics is consistent with nucleosynthesis constraint in these cases

  17. Pyoverdine, the Major Siderophore in Pseudomonas aeruginosa, Evades NGAL Recognition

    Directory of Open Access Journals (Sweden)

    Mary E. Peek

    2012-01-01

    Full Text Available Pseudomonas aeruginosa is the most common pathogen that persists in the cystic fibrosis lungs. Bacteria such as P. aeruginosa secrete siderophores (iron-chelating molecules and the host limits bacterial growth by producing neutrophil-gelatinase-associated lipocalin (NGAL that specifically scavenges bacterial siderophores, therefore preventing bacteria from establishing infection. P. aeruginosa produces a major siderophore known as pyoverdine, found to be important for bacterial virulence and biofilm development. We report that pyoverdine did not bind to NGAL, as measured by tryptophan fluorescence quenching, while enterobactin bound to NGAL effectively causing a strong response. The experimental data indicate that pyoverdine evades NGAL recognition. We then employed a molecular modeling approach to simulate the binding of pyoverdine to human NGAL using NGAL’s published crystal structures. The docking of pyoverdine to NGAL predicted nine different docking positions; however, neither apo- nor ferric forms of pyoverdine docked into the ligand-binding site in the calyx of NGAL where siderophores are known to bind. The molecular modeling results offer structural support that pyoverdine does not bind to NGAL, confirming the results obtained in the tryptophan quenching assay. The data suggest that pyoverdine is a stealth siderophore that evades NGAL recognition allowing P. aeruginosa to establish chronic infections in CF lungs.

  18. Supersensitive gastrin assay using antibodies raised against a cholecystokinin homolog

    DEFF Research Database (Denmark)

    Rehfeld, Jens F; Ericsson, Peter

    2012-01-01

    Peptide hormones may occur in particularly low amounts in samples from small animals. Hence, in a rat microdialysis study conventional immunoassays were not sufficiently sensitive to measure gastrin in the dialysis samples. We therefore exploited the observation that antibodies raised against...... that obtained with the most avid conventional gastrin antibodies. The results may encourage similar approaches for other peptides using homologue-raised antibodies when supersensitivity is required....

  19. Parasitic Cape honeybee workers, Apis mellifera capensis, evade policing

    Science.gov (United States)

    Martin, Stephen J.; Beekman, Madeleine; Wossler, Theresa C.; Ratnieks, Francis L. W.

    2002-01-01

    Relocation of the Cape honeybee, Apis mellifera capensis, by bee-keepers from southern to northern South Africa in 1990 has caused widespread death of managed African honeybee, A. m. scutellata, colonies. Apis mellifera capensis worker bees are able to lay diploid, female eggs without mating by means of automictic thelytoky (meiosis followed by fusion of two meiotic products to restore egg diploidy), whereas workers of other honeybee subspecies are able to lay only haploid, male eggs. The A. m. capensis workers, which are parasitizing and killing A. m. scutellata colonies in northern South Africa, are the asexual offspring of a single, original worker in which the small amount of genetic variation observed is due to crossing over during meiosis (P. Kryger, personal communication). Here we elucidate two principal mechanisms underlying this parasitism. Parasitic A. m. capensis workers activate their ovaries in host colonies that have a queen present (queenright colonies), and they lay eggs that evade being killed by other workers (worker policing)-the normal fate of worker-laid eggs in colonies with a queen. This unique parasitism by workers is an instance in which a society is unable to control the selfish actions of its members.

  20. SEROPREVALANCE OF TOXOPLASMA IgG AMONG PREGNANT WOMEN IN THE PROVINCE OF HATAY AND CONTRIBUTION OF AVIDITY TEST TO THE DIAGNOSE

    Directory of Open Access Journals (Sweden)

    Ayşe Güler Okyay

    2013-09-01

    Full Text Available Objective: Toxoplasma gondii, an obligate intracellular parasite, is a common zoonosis in the world and causes toxoplasmosis. The infection is usually asymptomatic and if it occurs during pregnancy it may cause congenital anomalies, miscarriage, stillbirth and premature delivery. In this study, determination of seroprevalance of Toxoplazma IgG and IgM among pregnant women in the province of Hatay was aimed. In addition, IgG avidity test was performed in subjects who had positive test results for both of the two antibodies. Design: In this study, 3340 pregnant women who admitted to the outpatient clinic of gynecelogy and obstetrics department of Mustafa Kemal University/Hatay between the years of 2007 and 2012were included. Toxoplazma IgM and IgG antibody test results of the subjects were examined retrospectively by screening the records of microbiology laboratory of the hospital. Additionally, IgG avidity test was performed in 114 cases whoose test results for both Toxoplazma IgM and IgG were positive. Main outcome measures: IgM and IgG seropositivity rates were found as 3.6% (n = 120 and 57% (n = 1910, respectively. The rate of new infection was detected with avidity test as 31%. Conclusions: Remarkably high seropositivity rate was observed in the Mediterranean region especially in the province of Hatay. Antibody testing for Toxoplasma gondii may be useful during routine examinations of women who are in the first trimester of pregnancy and who plan gestation. In addition, measures should be taken to raise awareness of hygiene in our region in terms of water and sanitation.

  1. DC8 and DC13 var genes associated with severe malaria bind avidly to diverse endothelial cells.

    Directory of Open Access Journals (Sweden)

    Marion Avril

    Full Text Available During blood stage infection, Plasmodium falciparum infected erythrocytes (IE bind to host blood vessels. This virulence determinant enables parasites to evade spleen-dependent killing mechanisms, but paradoxically in some cases may reduce parasite fitness by killing the host. Adhesion of infected erythrocytes is mediated by P. falciparum erythrocyte membrane protein 1 (PfEMP1, a family of polymorphic adhesion proteins encoded by var genes. Whereas cerebral binding and severe malaria are associated with parasites expressing DC8 and DC13 var genes, relatively little is known about the non-brain endothelial selection on severe malaria adhesive types. In this study, we selected P. falciparum-IEs on diverse endothelial cell types and demonstrate that DC8 and DC13 var genes were consistently among the major var transcripts selected on non-brain endothelial cells (lung, heart, bone marrow. To investigate the molecular basis for this avid endothelial binding activity, recombinant proteins were expressed from the predominant upregulated DC8 transcript, IT4var19. In-depth binding comparisons revealed that multiple extracellular domains from this protein bound brain and non-brain endothelial cells, and individual domains largely did not discriminate between different endothelial cell types. Additionally, we found that recombinant DC8 and DC13 CIDR1 domains exhibited a widespread endothelial binding activity and could compete for DC8-IE binding to brain endothelial cells, suggesting they may bind the same host receptor. Our findings provide new insights into the interaction of severe malaria adhesive types and host blood vessels and support the hypothesis that parasites causing severe malaria express PfEMP1 variants with a superior ability to adhere to diverse endothelial cell types, and may therefore endow these parasites with a growth and transmission advantage.

  2. Pärnus algavad homme Ungari kultuuripäevad / Teet Roossaar

    Index Scriptorium Estoniae

    Roossaar, Teet

    2005-01-01

    Ungari organist Miklos Teleki orelikontsertidest 3. sept. Eliisabeti kirikus ja 4. sept. Pärnu-Jaagupi kirikus ning Pärnu Linnaorkestri hooaja avakontserdist 4. sept. Pärnu kontserdimajas Ungari kultuuripäevade raames

  3. Linear Pursuit Differential Game under Phase Constraint on the State of Evader

    Directory of Open Access Journals (Sweden)

    Askar Rakhmanov

    2016-01-01

    Full Text Available We consider a linear pursuit differential game of one pursuer and one evader. Controls of the pursuer and evader are subjected to integral and geometric constraints, respectively. In addition, phase constraint is imposed on the state of evader, whereas pursuer moves throughout the space. We say that pursuit is completed, if inclusion y(t1-x(t1∈M is satisfied at some t1>0, where x(t and y(t are states of pursuer and evader, respectively, and M is terminal set. Conditions of completion of pursuit in the game from all initial points of players are obtained. Strategy of the pursuer is constructed so that the phase vector of the pursuer first is brought to a given set, and then pursuit is completed.

  4. XX rahvusvahelised trompetipäevad / Valdo Rüütelmaa

    Index Scriptorium Estoniae

    Rüütelmaa, Valdo

    2009-01-01

    17. märtsist kuni 5. aprillini Eesti Muusika- ja Teatriakadeemias toimunud rahvusvahelistest 20. trompetipäevadest, mille raames toimus 5. aprillil konkurss "Trompetitalendid 2009" . Trompetipäevade korraldaja Aavo Otsaga

  5. Tartu Kevadpäevad 2008 : Nädalajagu muusikat igale maitsele / Signe Tamberg

    Index Scriptorium Estoniae

    Tamberg, Signe

    2008-01-01

    Tartu Kevadpäevad 2008 muusikaprogrammis: 34. tudengilaulu võistlusest 29. apr. Tartu Sadamateatris, öölaulupeost 28. apr. Kassitoome orus, kontsertidest "Rokime!" 2. mail ja "Folgime" 3. mail Raekoja platsil

  6. Eesti Suusapäevad Jay Peak´is / Peeter Teedla ; fotod: Peeter Teedla

    Index Scriptorium Estoniae

    Teedla, Peeter

    2006-01-01

    märtsikuu esimesel nädalalõpul idaranniku eestlaste suusapäevad, osavõtjaid 156, paljud perekondade ja väikeste lastega, organiseerijaks Kristin Raamot. Peeti murdmaasuusatamise - ja slaalomivõistlused

  7. TACI deficiency enhances antibody avidity and clearance of an intestinal pathogen

    OpenAIRE

    Tsuji, Shoichiro; Stein, Lucas; Kamada, Nobuhiko; Nuñez, Gabriel; Bram, Richard; Vallance, Bruce A.; Sousa, Ana E.; Platt, Jeffrey L.; Cascalho, Marilia

    2014-01-01

    © 2014, The American Society for Clinical Investigation The transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) controls differentiation of long-lived plasma cells, and almost 10% of individuals with common variable immunodeficiency (CVID) express either the C104R or A181E variants of TACI. These variants impair TACI function, and TACI-deficient mice exhibit a CVID-like disease. However, 1%-2% of normal individuals harbor the C140R or A181E TACI variants and...

  8. Quantitative modeling assesses the contribution of bond strengthening, rebinding and force sharing to the avidity of biomolecule interactions.

    Directory of Open Access Journals (Sweden)

    Valentina Lo Schiavo

    Full Text Available Cell adhesion is mediated by numerous membrane receptors. It is desirable to derive the outcome of a cell-surface encounter from the molecular properties of interacting receptors and ligands. However, conventional parameters such as affinity or kinetic constants are often insufficient to account for receptor efficiency. Avidity is a qualitative concept frequently used to describe biomolecule interactions: this includes incompletely defined properties such as the capacity to form multivalent attachments. The aim of this study is to produce a working description of monovalent attachments formed by a model system, then to measure and interpret the behavior of divalent attachments under force. We investigated attachments between antibody-coated microspheres and surfaces coated with sparse monomeric or dimeric ligands. When bonds were subjected to a pulling force, they exhibited both a force-dependent dissociation consistent with Bell's empirical formula and a force- and time-dependent strengthening well described by a single parameter. Divalent attachments were stronger and less dependent on forces than monovalent ones. The proportion of divalent attachments resisting a force of 30 piconewtons for at least 5 s was 3.7 fold higher than that of monovalent attachments. Quantitative modeling showed that this required rebinding, i.e. additional bond formation between surfaces linked by divalent receptors forming only one bond. Further, experimental data were compatible with but did not require stress sharing between bonds within divalent attachments. Thus many ligand-receptor interactions do not behave as single-step reactions in the millisecond to second timescale. Rather, they exhibit progressive stabilization. This explains the high efficiency of multimerized or clustered receptors even when bonds are only subjected to moderate forces. Our approach provides a quantitative way of relating binding avidity to measurable parameters including bond

  9. Quantitative Modeling Assesses the Contribution of Bond Strengthening, Rebinding and Force Sharing to the Avidity of Biomolecule Interactions

    Science.gov (United States)

    Lo Schiavo, Valentina; Robert, Philippe; Limozin, Laurent; Bongrand, Pierre

    2012-01-01

    Cell adhesion is mediated by numerous membrane receptors. It is desirable to derive the outcome of a cell-surface encounter from the molecular properties of interacting receptors and ligands. However, conventional parameters such as affinity or kinetic constants are often insufficient to account for receptor efficiency. Avidity is a qualitative concept frequently used to describe biomolecule interactions: this includes incompletely defined properties such as the capacity to form multivalent attachments. The aim of this study is to produce a working description of monovalent attachments formed by a model system, then to measure and interpret the behavior of divalent attachments under force. We investigated attachments between antibody-coated microspheres and surfaces coated with sparse monomeric or dimeric ligands. When bonds were subjected to a pulling force, they exhibited both a force-dependent dissociation consistent with Bell’s empirical formula and a force- and time-dependent strengthening well described by a single parameter. Divalent attachments were stronger and less dependent on forces than monovalent ones. The proportion of divalent attachments resisting a force of 30 piconewtons for at least 5 s was 3.7 fold higher than that of monovalent attachments. Quantitative modeling showed that this required rebinding, i.e. additional bond formation between surfaces linked by divalent receptors forming only one bond. Further, experimental data were compatible with but did not require stress sharing between bonds within divalent attachments. Thus many ligand-receptor interactions do not behave as single-step reactions in the millisecond to second timescale. Rather, they exhibit progressive stabilization. This explains the high efficiency of multimerized or clustered receptors even when bonds are only subjected to moderate forces. Our approach provides a quantitative way of relating binding avidity to measurable parameters including bond maturation, rebinding and

  10. Compensating for cross-reactions using avidity and computation in a suspension multiplex immunoassay for serotyping of Zika versus other flavivirus infections.

    Science.gov (United States)

    Rönnberg, Bengt; Gustafsson, Åke; Vapalahti, Olli; Emmerich, Petra; Lundkvist, Åke; Schmidt-Chanasit, Jonas; Blomberg, Jonas

    2017-10-01

    The recent spread of Zika virus (ZIKV) in the Americas and Asia necessitates an increased preparedness for improved maternal and perinatal health and blood safety. However, serological cross-reactions, especially to Dengue virus (DENV), complicate ZIKV antibody serodiagnosis. A novel "pan-Flavi" suspension multiplex immunoassay (PFSMIA) using 25 antigens, whole virus (WV), non-structural protein 1 (NS1), and envelope (E) proteins, from 7 zoonotic flaviviruses for specific detection of ZIKV and DENV IgM and IgG was developed. Patterns of antibody cross-reactivity, avidity, and kinetics were established in 104 sera from returning travelers with known ZIKV and DENV infections. PFSMIA gave IgM- and IgG-sensitivities for both viruses of 96-100%, compared to an immunofluorescence assay. Main IgM cross-reactions were to NS1, for IgG to the E and WV antigens. Infecting virus yielded reactivity to several antigens of the homologous virus, while cross-reactions tended to occur only to a single antigen from heterologous virus(es). A specificity-enhancing computer procedure took into account antibody isotype, number of antibody-reactive antigens per virus, avidity, average degree of cross-reactivity to heterologous flavivirus antigens, and reactivity changes in serial sera. It classified all 50 cases correctly. Applied to sera from 200 pregnant women and 173 blood donors from Sweden, one blood donor was found ZIKV NS1 IgM positive, and another as ZIKV NS1 IgG positive. These samples did not react with other ZIKV antigens and were thereby judged as false-positives. PFSMIA provided sensitive and specific ZIKV and DENV serology, warranting high-throughput serological surveillance and a minimized need for laborious and expensive virus neutralization assays.

  11. Measles and canine distemper virus antibodies in patients with multiple sclerosis determined by radioimmunoassay

    International Nuclear Information System (INIS)

    Arnadottir, T.

    1980-01-01

    Antibodies against measles virus (MV) and canine distemper virus (CDV) were measured by solid-phase radioimmunoassay (RIA) of sera and cerebrospinal fluid (CSF) from 28 patients with multiple sclerosis (MS) and matched neurological controls. When the groups were compared for MV antibody titers and CDV antibody titers of sera and MV/CDV serum antibody titer ratios, no significant difference was found. The CDV antibody titers and the MV antibody titers were in good correlation. CDV antibodies showed RIA titration curves typical of low avidity antibodies. In tests for MV antibodies in CSF, 82% of the MS patients and 19% of the controls were positive, whereas 36% of the MS patients and 4% of the controls were positive in CDV RIA. The correlation between MV and CDV antibody levels, the low avidity of CDV antibodies and the fact that absorption of the specimens with MV antigen abolished all CDV antibody activity suggest that the CDV antibodies are MV antibodies cross-reacting with CDV. It is concluded that canine distemper virus is unlikely to be involved in the etiology of multiple sclerosis. (author)

  12. The hypervariable region of Streptococcus pyogenes M protein escapes antibody attack by antigenic variation and weak immunogenicity

    DEFF Research Database (Denmark)

    Lannergård, Jonas; Gustafsson, Caj Ulrik Mattias; Waldemarsson, Johan

    2011-01-01

    Sequence variation of antigenic proteins allows pathogens to evade antibody attack. The variable protein commonly includes a hypervariable region (HVR), which represents a key target for antibodies and is therefore predicted to be immunodominant. To understand the mechanism(s) of antibody evasion...

  13. CD8 T Cell Sensory Adaptation Dependent on TCR Avidity for Self-Antigens

    DEFF Research Database (Denmark)

    Marquez, M.-E.; Ellmeier, W.; Sanchez-Guajardo, Vanesa Maria

    2005-01-01

    dephosphorylation of linker for activation of T cells and ERK upon activation. Normal TCR levels and cytokine production were restored by culturing cells in the absence of TCR/spMHC interaction, demonstrating dynamic tuning of peripheral T cell responses. The effect of avidity for self-ligand(s) on this sensory...... ZAP-YEEI cells were enhanced. Our data provide support for central and peripheral sensory T cell adaptation induced as a function of TCR avidity for self-ligands and signaling level. This may contribute to buffer excessive autoreactivity while optimizing TCR repertoire usage....

  14. Eesti muusika päevad - üks kord aastas, kõigile / Jelena Gandshu

    Index Scriptorium Estoniae

    Gandshu, Jelena

    2008-01-01

    Muusikateadlased Jelena Gandshu ja Gerhard Lock, heliloojad Age Hirv ja Liis Jürgens 3.-10. aprillini toimunud Eesti muusika päevade kontsertidest: kinos Sõprus "Sensatsioon!!!", Kultuuritehases Polymer "Cellissimo", Estonia kontserdisaalis ERSO "Sümfoonilised hääled", Tallinna raekojas Mihkel Poll ja Oliver Kuusik, Katariina kirikus PaukenfEst, Nigulistes Jüri Reinvere autorikontsert. Järgneb

  15. Eesti Muusika Päevad 2000 : ECPNMi juhatus Tallinnas / Consuelo Diez ; interv. Evelin Kõrvits

    Index Scriptorium Estoniae

    Diez, Consuelo

    2000-01-01

    28.-30. apr. pidas Tallinnas aastakoosolekut ning külastas Eesti Muusika Päevade kontserte ECPNMi (European Conference of Promoters of New Music) juhatus. ECPNMi juhatuse liikmed räägivad uue muusika üritustest oma riikides, muljeid eesti muusika päevadelt

  16. Märtsipäevade valupisaraid peab lastele näitama / Anu Bollverk

    Index Scriptorium Estoniae

    Bollverk, Anu

    2009-01-01

    1949. aasta märtsiküüditamisele pühendatud mälestuspäevast Koeru kultuurimajas ning sealse huviteatri poolt ette kantud Herbert Lasti näidendist "Valupisarais märtsipäevad" (lavastajad Herbert Last ja Uno Aav)

  17. Why Do Firms Evade Taxes? The Role of Information Sharing and Financial Sector Outreach

    NARCIS (Netherlands)

    Beck, T.H.L.; Lin, C.; Ma, Y.

    2010-01-01

    Informality is a wide-spread phenomenon across the globe. We show that firms in countries with better information sharing systems and greater financial sector outreach evade taxes to a lesser degree, an effect that is stronger for smaller firms, firms in smaller cities and towns, and firms in

  18. Networks for Success: Preparing Mexican American AVID College Students for Credentials, Completion, and the Workforce

    Science.gov (United States)

    Kirk, Richard; Watt, Karen M.

    2018-01-01

    This qualitative study examines how Mexican American students participating in an AVID for Higher Education course perceived their preparation for the workforce and efficacy of completing a college credential. A focus group approach was used to explore how social and cultural networks (networks for success) contribute to college completion. The…

  19. Experimental evaluation of radioiodinated sennoside B as a necrosis-avid tracer agent.

    Science.gov (United States)

    Zhang, Dongjian; Huang, Dejian; Ji, Yun; Jiang, Cuihua; Li, Yue; Gao, Meng; Yao, Nan; Liu, Xuejiao; Shao, Haibo; Jing, Su; Ni, Yicheng; Yin, Zhiqi; Zhang, Jian

    2015-02-01

    Necrosis-avid agents are a class of compounds that selectively accumulate in the necrotic tissues after systemic administration, which can be used for in vivo necrosis imaging and targeted therapies. In order to search for a necrosis-avid tracer agent with improved drugability, we labelled iodine-131 on sennoside B (SB) as a naturally occurring median dianthrone compound. The necrosis targetability and clearance properties of (131)I-SB were evaluated in model rats with liver and muscle necrosis. On SPECT/CT images, a "hot spot" in the infarcted liver lobe and necrotic muscle was persistently observed at 24 h and 72 h post-injection (p.i.). Gamma counting of the tissues of interest revealed a radioactivity ratio of necrotic to viable liver at 4.6 and 3.4 and of necrotic to viable muscle at 7.0 and 8.8 at 24 h and 72 h p.i., respectively. The good match of autoradiographs and fluoromicroscopic images with corresponding histochemical staining suggested preferential uptake of (131)I-SB in necrotic tissue. Pharmacokinetic study revealed that (131)I-SB has an elimination half-life of 8.6 h. This study indicates that (131)I-SB shows not only prominent necrosis avidity but also favourable pharmacokinetics, which may serve as a potential necrosis-avid diagnostic agent for assessment of tissue viability.

  20. Benign Bone Conditions That May Be FDG-avid and Mimic Malignancy

    NARCIS (Netherlands)

    Kwee, Thomas C.; de Klerk, John M. H.; Nix, Maarten; Heggelman, Ben G. F.; Dubois, Stefan V.; Adams, Hugo J. A.

    Positron emission tomography with the radiotracer F-18-fluoro-2-deoxy-D-glucose (FDG) plays an important role in the evaluation of bone pathology. However, FDG is not a cancer-specific agent, and knowledge of the differential diagnosis of benign FDG-avid bone alterations that may resemble malignancy

  1. Ta(l)king sides: ethical and methodological challenges in comparative fieldwork on avid football rivalries

    NARCIS (Netherlands)

    Spaaij, R.; Geilenkirchen, M.

    2011-01-01

    Previous research on football (soccer) fan cultures has documented the lived experiences of devoted football supporters. Few studies, however, have used participant observation and intensive interviewing to examine the deep-rooted inter-group oppositions that characterize avid football rivalries.

  2. A new human IgG avidity test, using mixtures of recombinant antigens (rROP1, rSAG2, rGRA6), for the diagnosis of difficult-to-identify phases of toxoplasmosis.

    Science.gov (United States)

    Drapała, Dorota; Holec-Gąsior, Lucyna; Kur, Józef; Ferra, Bartłomiej; Hiszczyńska-Sawicka, Elżbieta; Lautenbach, Dariusz

    2014-07-01

    The preliminary diagnostic utility of two mixtures of Toxoplasma gondii recombinant antigens (rROP1+rSAG2 and rROP1+rGRA6) in IgG ELISA and IgG avidity test has been evaluated. A total of 173 serum samples from patients with toxoplasmosis and seronegative people were examined. The sensitivity of IgG ELISA for rROP1+rSAG2 and rROP1+rGRA6 was 91.1% and 76.7%, respectively, while the reactivity for sera from patients where acute toxoplasmosis was suspected was higher, at 100% and 95.4%, respectively, than for people with chronic infection, at 88.2% and 70.6%. In this study a different trend in avidity maturation of IgG antibodies for two mixtures of proteins in comparison with native antigen was observed. The results suggest that a new IgG avidity test using the mixtures of recombinant antigens may be useful for the diagnosis of difficult-to-identify phases of toxoplasmosis. For this reason, selected mixtures after the additional tests on groups of sera with well-defined dates of infection could be used as a better alternative to the native antigens of the parasite in the serodiagnosis of human T. gondii infection. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. evad : [luuletused] / Philip Larkin ; inglise keelest tlk. Maarja Kangro

    Index Scriptorium Estoniae

    Larkin, Philip

    2007-01-01

    Sisu: Päevad ; Mitte midagi öelda ; See olgu värss ; Uurimus lugemisharjumustest ; Hommage valitsusele ; Vesi ; Vajakud ; Viige üks koju lastele ; Jutt voodis ; Kõrged aknad ; Sa jätkad elu ; Kui. Orig.: Days ; Nothing to be said ; This be the verse ; A study of reading habits ; Homage to a government ; Water ; Wants ; Take one home for the kiddies ; Talking in bed ; High windows ; Continuing to live ; If

  4. DO PENALTIES AND ENFORCEMENT MEASURES MAKE TAXPAYERS MORE COMPLIANT? THE VIEW OF AUSTRALIAN TAX EVADERS

    OpenAIRE

    Dr Ken Devos

    2013-01-01

    The tax compliance literature indicates that many factors, including, economic, social, psychological and demographic, impact upon the compliance behaviour of individual taxpayers. This study explores the relationship, if any, that exists between selected tax compliance and demographic variables and the compliance behaviour of Australian individual tax evaders. The study employed a mixed method research approach comprising both a survey and interviews. The findings revealed that tax law enfor...

  5. FDG avidity and PET/CT patterns in primary gastric lymphoma

    International Nuclear Information System (INIS)

    Radan, Lea; Fischer, Doron; Bar-Shalom, Rachel; Israel, Ora; Dann, Eldad J.; Epelbaum, Ron; Haim, Nissim; Gaitini, Diana

    2008-01-01

    The use of 18F-fluoro-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in primary gastric lymphoma (PGL) is challenging due to physiologic FDG activity in the stomach and variability in the degree of uptake in various histologic subtypes. This study assesses FDG avidity and PET/CT patterns in newly diagnosed PGL. Sixty-two PET/CT studies of newly diagnosed PGL were reviewed (24 low-grade mucosa-associated lymphoid tissue [MALT], 38 aggressive non-Hodgkin's lymphoma [AGNHL]). FDG avidity, patterns (focal/diffuse), and intensity (visually vs. the liver and SUVmax) were assessed and compared to 27 controls. Gastric CT abnormalities and extragastric sites were recorded. Gastric FDG uptake was found in 55/62 (89%) PGL (71% MALT vs. 100% AGNHL, p < 0.001) and 63% controls. A diffuse pattern was found in 60% PGL (76% MALT vs. 53% AGNHL, p = NS) and 47% controls. FDG uptake higher than liver was found in 82% PGL (58% MALT vs. 97% AGNHL, p < 0.05) and 63% controls. SUVmax in FDG-avid PGLs was 15.3 ± 11.7 (5.4 ± 2.9 MALT vs. 19.7 ± 11.5 AGNHL, p < 0.001) and 4.6 ± 1.4 in controls. CT abnormalities were found in 79% PGL (thickening, n = 49; ulcerations, n = 22). Extra-gastric FDG-avid sites were seen in none of MALT, but 61% of AGNHL (nodal, n = 18; nodal and extranodal, n 5). FDG avidity was present in 89% of PGLs, including all patients with AGNHL but only 71% of MALT. FDG uptake can be differentiated, in particular in AGNHL-PGL, from physiologic tracer activity by intensity but not by pattern. Extragastric foci on PET and structural CT abnormalities are additional parameters that can improve PET/CT assessment of PGL. Defining FDG avidity and PET/CT patterns in AGNHL and a subgroup of MALT-PGL before treatment may be important for further monitoring therapy response. (orig.)

  6. FDG avidity and PET/CT patterns in primary gastric lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Radan, Lea [Rambam Health Care Campus, Department of Nuclear Medicine, Haifa (Israel); Fischer, Doron [Rambam Health Care Campus, Department of Diagnostic Imaging, Haifa (Israel); Bar-Shalom, Rachel; Israel, Ora [Technion - Israel Institute of Technology, Department of Nuclear Medicine, Rambam Health Care Campus and R. and B. Rappaport School of Medicine, Haifa (Israel); Dann, Eldad J. [Technion - Israel Institute of Technology, Department of Hematology, Rambam Health Care Campus, and R. and B. Rappaport School of Medicine, Haifa (Israel); Epelbaum, Ron; Haim, Nissim [Technion - Israel Institute of Technology, Department of Oncology, Rambam Health Care Campus, and R. and B. Rappaport School of Medicine, Haifa (Israel); Gaitini, Diana [Rambam Health Care Campus, and R. and B. Rappaport School of Medicine, Technion - Israel Institute of Technology, Department of Diagnostic Imaging, Haifa (Israel)

    2008-08-15

    The use of 18F-fluoro-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in primary gastric lymphoma (PGL) is challenging due to physiologic FDG activity in the stomach and variability in the degree of uptake in various histologic subtypes. This study assesses FDG avidity and PET/CT patterns in newly diagnosed PGL. Sixty-two PET/CT studies of newly diagnosed PGL were reviewed (24 low-grade mucosa-associated lymphoid tissue [MALT], 38 aggressive non-Hodgkin's lymphoma [AGNHL]). FDG avidity, patterns (focal/diffuse), and intensity (visually vs. the liver and SUVmax) were assessed and compared to 27 controls. Gastric CT abnormalities and extragastric sites were recorded. Gastric FDG uptake was found in 55/62 (89%) PGL (71% MALT vs. 100% AGNHL, p < 0.001) and 63% controls. A diffuse pattern was found in 60% PGL (76% MALT vs. 53% AGNHL, p = NS) and 47% controls. FDG uptake higher than liver was found in 82% PGL (58% MALT vs. 97% AGNHL, p < 0.05) and 63% controls. SUVmax in FDG-avid PGLs was 15.3 {+-} 11.7 (5.4 {+-} 2.9 MALT vs. 19.7 {+-} 11.5 AGNHL, p < 0.001) and 4.6 {+-} 1.4 in controls. CT abnormalities were found in 79% PGL (thickening, n = 49; ulcerations, n = 22). Extra-gastric FDG-avid sites were seen in none of MALT, but 61% of AGNHL (nodal, n = 18; nodal and extranodal, n = 5). FDG avidity was present in 89% of PGLs, including all patients with AGNHL but only 71% of MALT. FDG uptake can be differentiated, in particular in AGNHL-PGL, from physiologic tracer activity by intensity but not by pattern. Extragastric foci on PET and structural CT abnormalities are additional parameters that can improve PET/CT assessment of PGL. Defining FDG avidity and PET/CT patterns in AGNHL and a subgroup of MALT-PGL before treatment may be important for further monitoring therapy response. (orig.)

  7. Muusika : Jeremija nutulaulud palmipuudepühal. Jätkub "Musica Grande". Lihavõttetervitus Barcelonast. Rannap "Selges eesti helikeeles". Juba XIII trompetipäevad. III klavessiinipäevad / Jaan-Eik Tulve

    Index Scriptorium Estoniae

    Tulve, Jaan-Eik, 1967-

    2002-01-01

    Vox Clamantise kontsertidest Tartus ja Tallinnas. Jätkub sari "Musica Grande" kontsertidega Tartus ja Tallinnas pealkirjaga "Kontsertlik". Eestisse sõidab esinema üks Hispaania tippkoore Coral Cantiga Barcelonast. Rein Rannapi tänavusest suurprojektist, klaveriõhtust "Selges eesti helikeeles". 1. - 7. aprillini toimuvad EMA rahvusvahelised trompetipäevad. 4. - 7. aprillini korraldab Eesti Klavessiinisõprade Tsunft III klavessiinipäevad

  8. Antimitochondrial antibody

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003529.htm Antimitochondrial antibody To use the sharing features on this page, please enable JavaScript. Antimitochondrial antibodies (AMA) are substances ( antibodies ) that form against mitochondria. ...

  9. Human antibodies to immunoglobulin A (IgA)

    International Nuclear Information System (INIS)

    Munster, P.J.J. van; Nadorp, J.H.S.M.; Shuurman, H.J.

    1978-01-01

    In the sera of 12 out of 27 individuals with IgA deficiency (serum level below 0.02 mg IgA/m) class-specific anti-IgA antibodies were demonstrated by haemagglutination. These sera showed false-positive results in a solid-phase inhibition radioimmunoassay (RIST) (apparent IgA concentration between 0.6 and 13.7 μg IgA/ml) indicating that the RIST is not an appropriate test for the analysis of serum of IgA seficient individuals. A modification of the RIST is proposed (titration RIA) that permits differentiation between low levels of IgA and class-specific anti-IgA antibodies. With this test IgA deficient individuals could be classified as those with low but detectable levels of IgA and those with class-specific anti-IgA antibodies. A computer procedure was developed to calculate both the amount and the avidity (K) of the anti-IgA antibodies and to simulate the assay system. The K value calculated from experimental points proved to be an overestimation of the K value which fitted most adequately in the simulation. The comparison of the results with clinical findings indicated a possible correlation between the amount and the avidity of the anti-IgA antibodies and the appearence of anaphylactic reactions after transfusion of IgA. (Auth.)

  10. A high seroprevalence of antibodies to pertussis toxin among Japanese adults: Qualitative and quantitative analyses.

    Directory of Open Access Journals (Sweden)

    Takumi Moriuchi

    Full Text Available In 2013, national serosurveillance detected a high seroprevalence of antibodies to pertussis toxin (PT from Bordetella pertussis among Japanese adults. Thus, we aimed to determine the cause(s of this high seroprevalence, and analyzed the titers of antibodies to PT and filamentous hemagglutinin (FHA among adults (35-44 years old, young children (4-7 years old, and older children (10-14 years old. Our quantitative analyses revealed that adults had higher seroprevalences of anti-PT IgG and PT-neutralizing antibodies, and similar titers of anti-FHA IgG, compared to the young and older children. Positive correlations were observed between the titers of PT-neutralizing antibodies and anti-PT IgG in all age groups (rs values of 0.326-0.522, although the correlation tended to decrease with age. The ratio of PT-neutralizing antibodies to anti-PT IgG was significantly different when we compared the serum and purified IgG fractions among adults (p = 0.016, although this result was not observed among young and older children. Thus, it appears that some adults had non-IgG immunoglobulins to PT. Our analyses also revealed that adults had high-avidity anti-PT IgG (avidity index: 63.5%, similar results were observed among the children; however, the adults had lower-avidity anti-FHA IgG (37.9%, p < 0.05. It is possible that low-avidity anti-FHA IgG is related to infection with other respiratory pathogens (e.g., Bordetella parapertussis, Haemophilus influenzae, or Mycoplasma pneumoniae, which produces antibodies to FHA-like proteins. Our observations suggest that these adults had been infected with B. pertussis and other pathogen(s during their adulthood.

  11. Conformational occlusion of blockade antibody epitopes, a novel mechanism of GII.4 human norovirus immune evasion

    OpenAIRE

    Lindesmith, Lisa C.; Mallory, Michael L.; Debbink, Kari; Donaldson, Eric F.; Brewer-Jensen, Paul D.; Swann, Excel W.; Sheahan, Timothy P.; Graham, Rachel L.; Beltramello, Martina; Corti, Davide; Lanzavecchia, Antonio; Baric, Ralph S.

    2018-01-01

    ABSTRACT Extensive antigenic diversity within the GII.4 genotype of human norovirus is a major driver of pandemic emergence and a significant obstacle to development of cross-protective immunity after natural infection and vaccination. However, human and mouse monoclonal antibody studies indicate that, although rare, antibodies to conserved GII.4 blockade epitopes are generated. The mechanisms by which these epitopes evade immune surveillance are uncertain. Here, we developed a new approach f...

  12. Excretion and toxicity evaluation of 131I-Sennoside A as a necrosis-avid agent.

    Science.gov (United States)

    Yin, Zhiqi; Sun, Lidan; Jin, Qiaomei; Song, Shaoli; Feng, Yuanbo; Liao, Hong; Ni, Yicheng; Zhang, Jian; Liu, Wei

    2017-11-01

    1. Sennoside A (SA) is a newly identified necrosis-avid agent that shows capability for imaging diagnosis and tumor necrosis targeted radiotherapy. As a water-soluble compound, 131 I-Sennoside A ( 131 I-SA) might be excreted predominately through the kidneys with the possibility of nephrotoxicity. 2. To further verify excretion pathway and examine nephrotoxicity of 131 I-SA, excretion and nephrotoxicity were appraised. The pharmacokinetics, hepatotoxicity and hematotoxicity of 131 I-SA were also evaluated to accelerate its possible clinical translation. All these studies were conducted in mice with ethanol-induced muscular necrosis following a single intravenous administration of 131I-SA at 18.5 MBq/kg or 370 MBq/kg. 3. Excretion data revealed that 131 I-SA was predominately (73.5% of the injected dose (% ID)) excreted via the kidneys with 69.5% ID detected in urine within 72 h post injection. Biodistribution study indicated that 131 I-SA exhibited initial high distribution in the kidneys but subsequently a fast renal clearance, which was further confirmed by the results of autoradiography and single-photon emission computed tomography-computed tomography (SPECT-CT) imaging. The maximum necrotic to normal muscle ratio reached to 7.9-fold at 48 h post injection, which further verified the necrosis avidity of 131 I-SA. Pharmacokinetic parameters showed that 131 I-SA had fast blood clearance with an elimination half-life of 6.7 h. Various functional indexes were no significant difference (p > 0.05) between before administration and 1 d, 8 d, 16 d after administration. Histopathology showed no signs of tissue damage. 4. These data suggest 131 I-SA is a safe and promising necrosis-avid agent applicable in imaging diagnosis and tumor necrosis targeted radiotherapy.

  13. Motion-specific internal target volumes for FDG-avid mediastinal and hilar lymph nodes

    International Nuclear Information System (INIS)

    Lamb, James M.; Robinson, Clifford G.; Bradley, Jeffrey D.; Low, Daniel A.

    2013-01-01

    Background and purpose: To quantify the benefit of motion-specific internal target volumes for FDG-avid mediastinal and hilar lymph nodes generated using 4D-PET, vs. conventional internal target volumes generated using non-respiratory gated PET and 4D-CT scans. Materials and methods: Five patients with FDG-avid tumors metastatic to 11 hilar or mediastinal lymph nodes were imaged with respiratory-correlated FDG-PET (4D-PET) and 4D-CT. FDG-avid nodes were contoured by a radiation oncologist in two ways. Standard-of-care volumes were contoured using conventional un-gated PET, 4D-CT, and breath-hold CT. A second, motion-specific, set of volumes were contoured using 4D-PET.Contours based on 4D-PET corresponded directly to an internal target volume (ITV 4D ), whereas contours based on un-gated PET were expanded by a series of exploratory isotropic margins (from 5 to 13 mm) based on literature recommendations on lymph node motion to form internal target volumes (ITV 3D ). Results: A 13 mm expansion of the un-gated PET nodal volume was needed to cover the ITV 4D for 10 of 11 nodes studied. The ITV 3D based on a 13 mm expansion included on average 45 cm 3 of tissue that was not included in the ITV 4D . Conclusions: Motion-specific lymph-node internal target volumes generated from 4D-PET imaging could be used to improve accuracy and/or reduce normal-tissue irradiation compared to the standard-of-care un-gated PET based internal target volumes

  14. Clinical significance of pretreatment FDG PET/CT IN MOBG-avid pediatric neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Seo Young; Kim, Yong Il; Cheon, Gi Jeong; Kang, Keon Wook; Chung, June Key; Lee, Dong Soo; Kang, Hyoung Jin; Shin, Hee Young [Seoul National University Hospital, Seoul (Korea, Republic of); Kim, E. Edmund [Seoul National University, Seoul (Korea, Republic of); Rahim, Muhammad Kashif [Nishtar Medical College and Hospital, Multan (Pakistan)

    2017-06-15

    {sup 18}F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging is well known to have clinical significance in the initial staging and response evaluation of the many kinds of neoplasms. However, its role in the pediatric neuroblastoma is not clearly defined. In the present study, the clinical significance of FDG-PET/computed tomography (CT) in 123I- or 131I-metaiodobenzylguanidine (MIBG)-avid pediatric neuroblastoma was investigated. Twenty patients with neuroblastoma who undertook pretreatment FDG PET/CT at our institute between 2008 and 2015 and showed MIBG avidity were retrospectively enrolled in the present study. Clinical information—including histopathology, and serum markers—and several PET parameters—including SUVmax of the primary lesion (Psuv), target-to-background ratio (TBR), metabolic tumor volume (MTV), and coefficient of variation (CV)—were analyzed. The prognostic effect of PET parameters was evaluated in terms of progression-free survival (PFS). Total 20 patients (4.5 ± 3.5 years) were divided as two groups by disease progression. Six patients (30.0 %) experienced disease progression and one patient (5.0 %) died during follow-up period. There were not statistically significant in age, stage, MYCN status, primary tumor size, serum lactate dehydrogenase (LDH), neuron-specific enolase (NSE), and ferritin level between two groups with progression or no progression. However, Psuv (p = 0.017), TBR (p = 0.09), MTV (p = 0.02), and CV (p = 0.036) showed significant differences between two groups. In univariate analysis, PFS was significantly associated with Psuv (p = 0.021) and TBR (p = 0.023). FDG-PET parameters were significantly related with progression of neuroblastoma. FDG-PET/CT may have the potential as a valuable modality for evaluating prognosis in the patients with MIBG-avid pediatric neuroblastoma.

  15. MIBG avidity correlates with clinical features, tumor biology, and outcomes in neuroblastoma: A report from the Children's Oncology Group.

    Science.gov (United States)

    DuBois, Steven G; Mody, Rajen; Naranjo, Arlene; Van Ryn, Collin; Russ, Douglas; Oldridge, Derek; Kreissman, Susan; Baker, David L; Parisi, Marguerite; Shulkin, Barry L; Bai, Harrison; Diskin, Sharon J; Batra, Vandana; Maris, John M; Park, Julie R; Matthay, Katherine K; Yanik, Gregory

    2017-11-01

    Prior studies suggest that neuroblastomas that do not accumulate metaiodobenzylguanidine (MIBG) on diagnostic imaging (MIBG non-avid) may have more favorable features compared with MIBG avid tumors. We compared clinical features, biologic features, and clinical outcomes between patients with MIBG nonavid and MIBG avid neuroblastoma. Patients had metastatic high- or intermediate-risk neuroblastoma and were treated on Children's Oncology Group protocols A3973 or A3961. Comparisons of clinical and biologic features according to MIBG avidity were made with chi-squared or Fisher exact tests. Event-free (EFS) and overall (OS) survival compared using log-rank tests and modeled using Cox models. Thirty of 343 patients (8.7%) had MIBG nonavid disease. Patients with nonavid tumors were less likely to have adrenal primary tumors (34.5 vs. 57.2%; P = 0.019), bone metastases (36.7 vs. 61.7%; P = 0.008), or positive urine catecholamines (66.7 vs. 91.0%; P neuroblastoma have lower rates of adrenal primary tumors, bone metastasis, and catecholamine secretion. Despite being more likely to have MYCN-amplified tumors, these patients have superior outcomes compared with patients with MIBG avid disease. © 2017 Wiley Periodicals, Inc.

  16. Antibody biotechnology

    African Journals Online (AJOL)

    STORAGESEVER

    2009-07-06

    Jul 6, 2009 ... Another milestone in the history of antibodies was the work of Porter and Edelman ... transgenic animals (Lonberg et al., 1994; Green et al.,. 1994) or .... create and to screen human recombinant antibodies libraries, that is ...

  17. Antithyroid microsomal antibody

    Science.gov (United States)

    Thyroid antimicrosomal antibody; Antimicrosomal antibody; Microsomal antibody; Thyroid peroxidase antibody; TPOAb ... Granulomatous thyroiditis Hashimoto thyroiditis High levels of these antibodies have also been linked with an increased risk ...

  18. Thyroid Antibodies

    Science.gov (United States)

    ... PF4 Antibody Hepatitis A Testing Hepatitis B Testing Hepatitis C Testing HER2/neu Herpes Testing High-sensitivity C-reactive Protein (hs-CRP) Histamine Histone Antibody HIV Antibody and HIV Antigen (p24) HIV Antiretroviral Drug Resistance Testing, Genotypic HIV Viral Load HLA Testing HLA- ...

  19. How type 1 fimbriae help Escherichia coli to evade extracellular antibiotics.

    Science.gov (United States)

    Avalos Vizcarra, Ima; Hosseini, Vahid; Kollmannsberger, Philip; Meier, Stefanie; Weber, Stefan S; Arnoldini, Markus; Ackermann, Martin; Vogel, Viola

    2016-01-05

    To survive antibiotics, bacteria use two different strategies: counteracting antibiotic effects by expression of resistance genes or evading their effects e.g. by persisting inside host cells. Since bacterial adhesins provide access to the shielded, intracellular niche and the adhesin type 1 fimbriae increases bacterial survival chances inside macrophages, we asked if fimbriae also influenced survival by antibiotic evasion. Combined gentamicin survival assays, flow cytometry, single cell microscopy and kinetic modeling of dose response curves showed that type 1 fimbriae increased the adhesion and internalization by macrophages. This was caused by strongly decreased off-rates and affected the number of intracellular bacteria but not the macrophage viability and morphology. Fimbriae thus promote antibiotic evasion which is particularly relevant in the context of chronic infections.

  20. The atherogenic bacterium Porphyromonas gingivalis evades circulating phagocytes by adhering to erythrocytes

    DEFF Research Database (Denmark)

    Belstrøm, Daniel; Holmstrup, Palle; Damgaard, Christian

    2011-01-01

    A relationship between periodontitis and coronary heart disease has been investigated intensively. A pathogenic role for the oral bacterium Porphyromonas gingivalis has been suggested for both diseases. We examined whether complement activation by P. gingivalis strain ATCC 33277 allows...... the bacterium to adhere to human red blood cells (RBCs) and thereby evade attack by circulating phagocytes. On incubation with normal human serum, the P. gingivalis strain efficiently fixed complement component 3 (C3). Incubation of bacteria with washed whole blood cells suspended in autologous serum resulted...... in a dose- and time-dependent adherence to RBCs. The adherence required functionally intact complement receptor 1 (CR1; also called CD35) on the RBCs and significantly inhibited the uptake of P. gingivalis by neutrophils and B cells within 1 min of incubation (by 64% and 51%, respectively...

  1. Evading the pulsar constraints on the cosmic string tension in supergravity inflation

    Energy Technology Data Exchange (ETDEWEB)

    Kamada, Kohei [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Miyamoto, Yuhei [Tokyo Univ. (Japan). Dept. of Physics; Tokyo Univ. (JP). Research Center for the Early Universe (RESCEU); Yokoyama, Jun' ichi [Tokyo Univ. (JP). Research Center for the Early Universe (RESCEU); Tokyo Univ., Kashiwa, Chiba (JP). Inst. for the Physics and Mathematics of the Universe (IPMU)

    2012-04-15

    The cosmic string is a useful probe of the early Universe and may give us a clue to physics at high energy scales where any artificial particle accelerators cannot reach. Although one of the most promising tools is the cosmic microwave background, the constraint from gravitational waves is becoming so stringent that one may not hope to detect its signatures in the cosmic microwave background. In this paper, we construct a scenario that contains cosmic strings observable in the cosmic microwave background while evading the constraint imposed by the recent pulsar timing data. We argue that cosmic strings with relatively large tension are allowed by delaying the onset of the scaling regime. We also show that this scenario is naturally realized in the context of chaotic inflation in supergravity, where the phase transition is governed by the Hubble induced mass.

  2. Evading the pulsar constraints on the cosmic string tension in supergravity inflation

    International Nuclear Information System (INIS)

    Kamada, Kohei; Miyamoto, Yuhei; Yokoyama, Jun'ichi

    2012-04-01

    The cosmic string is a useful probe of the early Universe and may give us a clue to physics at high energy scales where any artificial particle accelerators cannot reach. Although one of the most promising tools is the cosmic microwave background, the constraint from gravitational waves is becoming so stringent that one may not hope to detect its signatures in the cosmic microwave background. In this paper, we construct a scenario that contains cosmic strings observable in the cosmic microwave background while evading the constraint imposed by the recent pulsar timing data. We argue that cosmic strings with relatively large tension are allowed by delaying the onset of the scaling regime. We also show that this scenario is naturally realized in the context of chaotic inflation in supergravity, where the phase transition is governed by the Hubble induced mass.

  3. First preclinical evaluation of mono-[123I]iodohypericin as a necrosis-avid tracer agent

    International Nuclear Information System (INIS)

    Ni, Yicheng; Chen, Feng; Marchal, Guy; Huyghe, Dieter; Verbeke, Kristin; Verbruggen, Alfons M.; Bormans, Guy M.; Witte, Peter A. de; Nuyts, Johan; Mortelmans, Luc

    2006-01-01

    We have labelled hypericin, a polyphenolic polycyclic quinone found in St. John's wort (Hypericum perforatum), with 123 I and evaluated mono-[ 123 I]iodohypericin (MIH) as a potential necrosis-avid diagnostic tracer agent. MIH was prepared by an electrophilic radioiodination method. The new tracer agent was evaluated in animal models of liver infarction in the rat and heart infarction in the rabbit using single-photon emission computed tomography (SPECT), triphenyltetrazolium chloride (TTC) histochemical staining, serial sectional autoradiography and microscopy, and radioactivity counting techniques. Using in vivo SPECT imaging, hepatic and cardiac infarctions were persistently visualised as well-defined hot spots over 48 h. Preferential uptake of the tracer agent in necrotic tissue was confirmed by perfect match of images from post-mortem TTC staining, autoradiography (ARX) and histology. Radioactivity concentration in infarcted tissues was over 10 times (liver; 3.51% ID/g in necrotic tissue vs 0.38% ID/g in normal tissue at 60 h p.i.) and over 6 times (myocardium; 0.36% ID/g in necrotic tissue vs 0.054% ID/g in normal tissue; ratios up to 18 for selected parts on ARX images) higher than in normal tissues. The results suggest that hypericin derivatives may serve as powerful necrosis-avid diagnostic agents for assessment of tissue viability. (orig.)

  4. The tyrosine B10 hydroxyl is crucial for oxygen avidity of Ascaris hemoglobin.

    Science.gov (United States)

    Kloek, A P; Yang, J; Mathews, F S; Frieden, C; Goldberg, D E

    1994-01-28

    The parasitic nematode Ascaris suum has a gene encoding a two-domain hemoglobin with remarkable oxygen avidity. The strong interaction with oxygen is a consequence of a particularly slow oxygen off-rate. The single polypeptide chain consists of two domains, each of which can be expressed separately in Escherichia coli as a globin-like protein exhibiting oxygen binding characteristics comparable with the native molecule. Site-directed mutagenesis was performed on the gene segment encoding domain one. The E7 position, involved in forming a hydrogen bond with the liganded oxygen in vertebrate globins, is a glutamine in both Ascaris domains. Conversion of this residue to leucine or alanine produced a hemoglobin variant with an oxygen off-rate 5- or 60-fold faster than that of unaltered domain one. Replacement of the tyrosine B10 with either phenylalanine or leucine (as found in vertebrate globins) yielded hemoglobin mutants with oxygen off-rates 280- or 570-fold faster, approaching rates found with vertebrate myoglobins. The data suggest that the distal glutamine hydrogen bonds with the liganded oxygen and that the tyrosine B10 hydroxyl contributes an additional hydrogen bond that appears substantially responsible for the extreme oxygen avidity of Ascaris hemoglobin.

  5. Analysis of mumps vaccine failure by means of avidity testing for mumps virus-specific immunoglobulin G.

    Science.gov (United States)

    Narita, M; Matsuzono, Y; Takekoshi, Y; Yamada, S; Itakura, O; Kubota, M; Kikuta, H; Togashi, T

    1998-11-01

    To characterize patients with mumps vaccine failure, avidity testing was performed with the Enzygnost Anti-Parotitis Virus/IgG kit using a single-dilution-6 M urea denaturation method. Five groups of patients were tested. Group 1 consisted of 29 patients with primary mumps infections; group 2 was 20 children and adults with a definite history of natural infection; group 3 was 7 patients with a recent mumps vaccination, 1 of whom developed parotid gland swelling and aseptic meningitis; group 4 was 14 patients with mumps vaccine failure; and group 5 was 6 patients with recurrent episodes of parotitis in addition to a history of vaccination. On the basis of the results of groups 1 and 2, an avidity of /=32% was determined to be high. Avidity maturation from low to high appears to occur around 180 days after the acute illness. The results of group 3 showed that the vaccine-induced immunoglobulin G (IgG) had very low avidity. Among the 14 patients in group 4, 12 patients, including 7 with a positive IgM response, were diagnosed as having secondary vaccine failures. The results of group 5 suggested the possibility that the avidity of the mumps vaccine-induced IgG remains low or borderline. These results showed that secondary mumps vaccine failure occurs not infrequently, even among school age children under condition in which the vaccine coverage is low (i.e., 33% in our study population), and therefore, vaccinees are prone to be exposed to wild-type viruses. Avidity testing should provide information useful for the analysis of mumps virus infections.

  6. Avidity of IgG for rubella: an evaluation of the need for implementation at the Materno-Infantil Presidente Vargas Hospital in Porto Alegre, Rio Grande do Sul, Brazil

    Directory of Open Access Journals (Sweden)

    M.M. Reis

    Full Text Available Rubella serum assays performed in the laboratory of the Materno-Infantil Presidente Vargas Hospital (HMIPV from 1998 to 2002 were reviewed to determine if IgG avidity assays should be implemented. IgG was determined using the Enzyme Linked Fluorescent Assay, ELFA, VIDAS® system, bioMérieux or the Microparticle Enzyme Immunoassay, MEIA, Axsym® system, Abbott, and IgM was determined using the ELFA, VIDAS® system, bioMérieux, a capture format assay. Specific IgG was assayed in 2,863 samples, with positive results for 84% of the patients, for the most part with high levels of antibodies. IgM was assayed in 2,851 samples, being positive in 14 (0.49% and inconclusive in 25 (0.88%. Serology for toxoplasmosis was also positive or inconclusive in 5 patients. After a cost-effectiveness analysis, it was decided not to implement avidity assays, considering that the HMIPV is a public institution, with limited funding. Difficulties concerning the integration of the Clinical Pathology Service with the Clinical Staff of the institution were also considered.

  7. Lübecki filmipäevad 1999 ja Thomas Manni ekraniseering 1923 / Lauri Kärk

    Index Scriptorium Estoniae

    Kärk, Lauri, 1954-

    1999-01-01

    4.-7. novembrini Lübeckis toimunud Põhjamaade filmipäevade 41. Nordische Filmtage huvitavamatest filmidest, nagu Thomas Manni "Buddenbrookide" ekraniseering 1923. aastast (režissöör Gerhard Lamprecht) ja Rasmus Gerlachi dokumentaal "Operaator Kaufman" Dziga Vertovist ja tema kahest, samuti kino alal tegutsenud vennast

  8. Radiolabeled Rhein as Small-Molecule Necrosis Avid Agents for Imaging of Necrotic Myocardium.

    Science.gov (United States)

    Luo, Qi; Jin, Qiaomei; Su, Chang; Zhang, Dongjian; Jiang, Cuihua; Fish, Anne Folta; Feng, Yuanbo; Ni, Yicheng; Zhang, Jian; Yin, Zhiqi

    2017-01-17

    A rapid and accurate identification of necrotic myocardium is of great importance for diagnosis, risk stratification, clinical decision-making, and prognosis evaluation of myocardial infarction. Here, we explored technetium-99m labeled rhein derivatives for rapid imaging of the necrotic myocardium. Three hydrazinonicotinic acid-linker-rhein (HYNIC-linker-rhein) derivatives were synthesized, and then, these synthetic compounds were labeled with technetium-99m using ethylenediaminediacetic acid (EDDA) and tricine as coligands [ 99m Tc(EDDA)-HYNIC-linker-rhein]. The necrosis avidity of the three 99m Tc-labeled rhein derivatives was tested in a mouse model of ethanol-induced muscular necrosis by gamma counting, histochemical staining, and autoradiography. A lead tracer for visualization of necrotic myocardium was assessed by single photon emission computed tomography/computed tomography (SPECT/CT) imaging in a rat model with reperfused myocardial infarction. The necrosis avidity mechanism of the tracer was explored by DNA binding studies in vitro and blocking experiments in vivo. Results showed that the uptake in necrotic muscles of the three 99m Tc-compounds was higher than that in viable muscles (P EDDA)-HYNIC-ethylenediamine-rhein [ 99m Tc(EDDA)-HYNIC-2C-rhein] displayed the best distribution profiles for imaging. The necrotic myocardium lesions were clearly visualized by SPECT/CT using 99m Tc(EDDA)-HYNIC-2C-rhein at 1 h after injection. The necrotic-to-viable myocardium and necrotic myocardium-to-blood uptake ratios of 99m Tc(EDDA)-HYNIC-2C-rhein were 4.79 and 3.02 at 1 h after injection. DNA binding studies suggested HYNIC-linker-rhein bound to DNA through intercalation. The uptake of 99m Tc(EDDA)-HYNIC-2C-rhein in necrotic muscle was significantly blocked by excessive unlabeled rhein, with 77.61% decline at 1 h after coinjection. These findings suggested 99m Tc(EDDA)-HYNIC-2C-rhein emerged as a "hot spot" imaging probe that has a potential for rapid imaging of

  9. Use of IgG avidity ELISA to differentiate acute from persistent infection with Salmonella Dublin in cattle

    DEFF Research Database (Denmark)

    Hansen, K.R.; Nielsen, L.R.; Lind, Peter

    2006-01-01

    Aims: To investigate whether an immunoglobulin (Ig)G avidity ELISA can be used to differentiate between acute and persistent infection with Salmonella (S.) Dublin in cattle. To determine whether the IgG isotype, IgG(1) and IgG(2) responses in acute and persistent infections differ. Methods...

  10. IgG avidity to Pseudomonas aeruginosa over the course of chronic lung biofilm infection in cystic fibrosis

    DEFF Research Database (Denmark)

    Mauch, Renan Marrichi; Nørregaard, Lena Lingren; Ciofu, Oana

    2018-01-01

    Background and objectives: The mechanisms leading to low effectiveness of the humoral immune response against P. aeruginosa in cystic fibrosis (CF) are poorly understood. The aim of the present study was to assess the avidity maturation of specific antipseudomonal IgG before and during the develo...

  11. HIV avidity index performance using a modified fourth-generation immunoassay to detect recent HIV infections.

    Science.gov (United States)

    Suligoi, Barbara; Regine, Vincenza; Raimondo, Mariangela; Rodella, Anna; Terlenghi, Luigina; Caruso, Arnaldo; Bagnarelli, Patrizia; Capobianchi, Maria Rosaria; Zanchetta, Nadia; Ghisetti, Valeria; Galli, Claudio

    2017-10-26

    Detecting recent HIV infections is important to evaluate incidence and monitor epidemic trends. We aimed to evaluate the diagnostic performance and accuracy of the avidity index (AI) for discriminating for recent HIV infections. We collected serum samples from HIV-1 positive individuals: A) with known date of infection (midpoint in time between last HIV-negative and first HIV-positive test); B) infected for >1 year. Samples were divided into two aliquots: one diluted with phosphate buffered saline (PBS) and the other with 1 M guanidine. Both aliquots were assayed by the Architect HIV Ag/Ab Combo 4th generation assay (Abbott). We compared AI found in recent (RI=HIV subtype had no impact on AI misclassifications. All individuals in group A reached the AI threshold of 0.80 within 24 months after seroconversion. The AI is an accurate serological marker for discriminating recent from established HIV infections and meets WHO requirements for HIV incidence assays.

  12. Antiprothrombin Antibodies

    Directory of Open Access Journals (Sweden)

    Polona Žigon

    2015-05-01

    Full Text Available In patients with the antiphospholipid syndrome (APS, the presence of a group of pathogenic autoantibodies called antiphospholipid antibodies causes thrombosis and pregnancy complications. The most frequent antigenic target of antiphospholipid antibodies are phospholipid bound β2-glycoprotein 1 (β2GPI and prothrombin. The international classification criteria for APS connect the occurrence of thrombosis and/or obstetric complications together with the persistence of lupus anticoagulant, anti-cardiolipin antibodies (aCL and antibodies against β2GPI (anti-β2GPI into APS. Current trends for the diagnostic evaluation of APS patients propose determination of multiple antiphospholipid antibodies, among them also anti-prothrombin antibodies, to gain a common score which estimates the risk for thrombosis in APS patients. Antiprothrombin antibodies are common in APS patients and are sometimes the only antiphospholipid antibodies being elevated. Methods for their determination differ and have not yet been standardized. Many novel studies confirmed method using phosphatidylserine/prothrombin (aPS/PT ELISA as an antigen on solid phase encompass higher diagnostic accuracy compared to method using prothrombin alone (aPT ELISA. Our research group developed an in-house aPS/PT ELISA with increased analytical sensitivity which enables the determination of all clinically relevant antiprothrombin antibodies. aPS/PT exhibited the highest percentage of lupus anticoagulant activity compared to aCL and anti-β2GPI. aPS/PT antibodies measured with the in-house method associated with venous thrombosis and presented the strongest independent risk factor for the presence of obstetric complications among all tested antiphospholipid antibodies

  13. The influence of dengue virus serotype-2 infection on Aedes aegypti (Diptera: Culicidae motivation and avidity to blood feed.

    Directory of Open Access Journals (Sweden)

    Rafael Maciel-de-Freitas

    Full Text Available BACKGROUND: Dengue virus (DENV is transmitted by Aedes aegypti, a species that lives in close association with human dwellings. The behavior of DENV-infected mosquitoes needs further investigation, especially regarding the potential influence of DENV on mosquito biting motivation and avidity. METHODOLOGY/PRINCIPAL FINDINGS: We orally challenged 4-5 day-old Ae. aegypti females with a low passage DENV serotype -2 (DENV-2 to test whether the virus influences motivation to feed (the likelihood that a mosquito obtains a blood-meal and the size of its blood meal and avidity (the likelihood to re-feed after an interrupted first blood-meal. To assay motivation, we offered mosquitoes an anesthetized mouse for 2, 3, 4 or 5 minutes 7 or 14 days after the initial blood meals and measured the time they started feeding. 60.5% of the unexposed mosquitoes fed on the mouse, but only 40.5% of the positive ones did. Exposed but negative mosquitoes behaved similarly to unexposed ones (55.0% feeding. Thus DENV-2 infection decreased the mosquitoes' motivation to feed. To assay avidity, we offered the same mosquitoes a mouse two hours after the first round of feeding, and we measured the time at which they started probing. The exposed (positive or negative mosquitoes were more likely to re-feed than the unexposed ones and, in particular, the size of the previous blood-meal that kept mosquitoes from re-feeding was larger in the exposed than in the unexposed mosquitoes. Thus, DENV-2 infection increased mosquito avidity. CONCLUSIONS/SIGNIFICANCE: DENV-2 significantly decreased the mosquitoes' motivation to feed, but increased their avidity (even after taking account the amount of blood previously imbibed. As these are important components of transmission, we expect that the changes of the blood-feeding behaviour impact the vectorial capacity Ae. aegypti for dengue.

  14. The influence of dengue virus serotype-2 infection on Aedes aegypti (Diptera: Culicidae) motivation and avidity to blood feed.

    Science.gov (United States)

    Maciel-de-Freitas, Rafael; Sylvestre, Gabriel; Gandini, Mariana; Koella, Jacob C

    2013-01-01

    Dengue virus (DENV) is transmitted by Aedes aegypti, a species that lives in close association with human dwellings. The behavior of DENV-infected mosquitoes needs further investigation, especially regarding the potential influence of DENV on mosquito biting motivation and avidity. We orally challenged 4-5 day-old Ae. aegypti females with a low passage DENV serotype -2 (DENV-2) to test whether the virus influences motivation to feed (the likelihood that a mosquito obtains a blood-meal and the size of its blood meal) and avidity (the likelihood to re-feed after an interrupted first blood-meal). To assay motivation, we offered mosquitoes an anesthetized mouse for 2, 3, 4 or 5 minutes 7 or 14 days after the initial blood meals and measured the time they started feeding. 60.5% of the unexposed mosquitoes fed on the mouse, but only 40.5% of the positive ones did. Exposed but negative mosquitoes behaved similarly to unexposed ones (55.0% feeding). Thus DENV-2 infection decreased the mosquitoes' motivation to feed. To assay avidity, we offered the same mosquitoes a mouse two hours after the first round of feeding, and we measured the time at which they started probing. The exposed (positive or negative) mosquitoes were more likely to re-feed than the unexposed ones and, in particular, the size of the previous blood-meal that kept mosquitoes from re-feeding was larger in the exposed than in the unexposed mosquitoes. Thus, DENV-2 infection increased mosquito avidity. DENV-2 significantly decreased the mosquitoes' motivation to feed, but increased their avidity (even after taking account the amount of blood previously imbibed). As these are important components of transmission, we expect that the changes of the blood-feeding behaviour impact the vectorial capacity Ae. aegypti for dengue.

  15. Henipaviruses Employ a Multifaceted Approach to Evade the Antiviral Interferon Response

    Directory of Open Access Journals (Sweden)

    Megan L. Shaw

    2009-12-01

    Full Text Available Hendra and Nipah virus, which constitute the genus Henipavirus, are zoonotic paramyxoviruses that have been associated with sporadic outbreaks of severe disease and mortality in humans since their emergence in the late 1990s. Similar to other paramyxoviruses, their ability to evade the host interferon (IFN response is conferred by the P gene. The henipavirus P gene encodes four proteins; the P, V, W and C proteins, which have all been described to inhibit the antiviral response. Further studies have revealed that these proteins have overlapping but unique properties which enable the virus to block multiple signaling pathways in the IFN response. The best characterized of these is the JAK-STAT signaling pathway which is targeted by the P, V and W proteins via an interaction with the transcription factor STAT1. In addition the V and W proteins can both limit virus-induced induction of IFN but they appear to do this via distinct mechanisms that rely on unique sequences in their C-terminal domains. The ability to generate recombinant Nipah viruses now gives us the opportunity to determine the precise role for each of these proteins and address their contribution to pathogenicity. Additionally, the question of whether these multiple anti-IFN strategies are all active in the different mammalian hosts for henipaviruses, particularly the fruit bat reservoir, warrants further exploration.

  16. Quantum back-action-evading measurement of motion in a negative mass reference frame

    Science.gov (United States)

    Møller, Christoffer B.; Thomas, Rodrigo A.; Vasilakis, Georgios; Zeuthen, Emil; Tsaturyan, Yeghishe; Balabas, Mikhail; Jensen, Kasper; Schliesser, Albert; Hammerer, Klemens; Polzik, Eugene S.

    2017-07-01

    Quantum mechanics dictates that a continuous measurement of the position of an object imposes a random quantum back-action (QBA) perturbation on its momentum. This randomness translates with time into position uncertainty, thus leading to the well known uncertainty on the measurement of motion. As a consequence of this randomness, and in accordance with the Heisenberg uncertainty principle, the QBA puts a limitation—the so-called standard quantum limit—on the precision of sensing of position, velocity and acceleration. Here we show that QBA on a macroscopic mechanical oscillator can be evaded if the measurement of motion is conducted in the reference frame of an atomic spin oscillator. The collective quantum measurement on this hybrid system of two distant and disparate oscillators is performed with light. The mechanical oscillator is a vibrational ‘drum’ mode of a millimetre-sized dielectric membrane, and the spin oscillator is an atomic ensemble in a magnetic field. The spin oriented along the field corresponds to an energetically inverted spin population and realizes a negative-effective-mass oscillator, while the opposite orientation corresponds to an oscillator with positive effective mass. The QBA is suppressed by -1.8 decibels in the negative-mass setting and enhanced by 2.4 decibels in the positive-mass case. This hybrid quantum system paves the way to entanglement generation and distant quantum communication between mechanical and spin systems and to sensing of force, motion and gravity beyond the standard quantum limit.

  17. Quantum back-action-evading measurement of motion in a negative mass reference frame.

    Science.gov (United States)

    Møller, Christoffer B; Thomas, Rodrigo A; Vasilakis, Georgios; Zeuthen, Emil; Tsaturyan, Yeghishe; Balabas, Mikhail; Jensen, Kasper; Schliesser, Albert; Hammerer, Klemens; Polzik, Eugene S

    2017-07-12

    Quantum mechanics dictates that a continuous measurement of the position of an object imposes a random quantum back-action (QBA) perturbation on its momentum. This randomness translates with time into position uncertainty, thus leading to the well known uncertainty on the measurement of motion. As a consequence of this randomness, and in accordance with the Heisenberg uncertainty principle, the QBA puts a limitation-the so-called standard quantum limit-on the precision of sensing of position, velocity and acceleration. Here we show that QBA on a macroscopic mechanical oscillator can be evaded if the measurement of motion is conducted in the reference frame of an atomic spin oscillator. The collective quantum measurement on this hybrid system of two distant and disparate oscillators is performed with light. The mechanical oscillator is a vibrational 'drum' mode of a millimetre-sized dielectric membrane, and the spin oscillator is an atomic ensemble in a magnetic field. The spin oriented along the field corresponds to an energetically inverted spin population and realizes a negative-effective-mass oscillator, while the opposite orientation corresponds to an oscillator with positive effective mass. The QBA is suppressed by -1.8 decibels in the negative-mass setting and enhanced by 2.4 decibels in the positive-mass case. This hybrid quantum system paves the way to entanglement generation and distant quantum communication between mechanical and spin systems and to sensing of force, motion and gravity beyond the standard quantum limit.

  18. Stealth nanotubes: strategies of shielding carbon nanotubes to evade opsonization and improve biodistribution

    Science.gov (United States)

    Kotagiri, Nalinikanth; Kim, Jin-Woo

    2014-01-01

    Carbon nanotubes (CNTs) have recently been in the limelight for their potential role in disease diagnostics and therapeutics, as well as in tissue engineering. Before these medical applications can be realized, there is a need to address issues like opsonization, phagocytosis by macrophages, and sequestration to the liver and spleen for eventual elimination from the body; along with equally important issues such as aqueous solubility, dispersion, biocompatibility, and biofunctionalization. CNTs have not been shown to be able to evade such biological obstacles, which include their nonspecific attachments to cells and other biological components in the bloodstream, before reaching target tissues and cells in vivo. This will eventually determine their longevity in circulation and clearance rate from the body. This review article discusses the current status, challenges, practical strategies, and implementations of coating CNTs with biocompatible and opsonin-resistant moieties, rendering CNTs transparent to opsonins and deceiving the innate immune response to make believe that the CNTs are not foreign. A holistic approach to the development of such “stealth” CNTs is presented, which encompasses not only several biophysicochemical factors that are not limited to surface treatment of CNTs, but also extraneous biological factors such as the protein corona formation that inevitably controls the in vivo fate of the particles. This review also discusses the present and potential applications, along with the future directions, of CNTs and their hybrid-based nanotheranostic agents for multiplex, multimodal molecular imaging and therapy, as well as in other applications, such as drug delivery and tissue engineering. PMID:24872705

  19. Stealth nanotubes: strategies of shielding carbon nanotubes to evade opsonization and improve biodistribution

    Directory of Open Access Journals (Sweden)

    Kotagiri N

    2014-05-01

    Full Text Available Nalinikanth Kotagiri,1–4 Jin-Woo Kim1–31Bio/Nano Technology Laboratory, Institute for Nanoscience and Engineering, 2Department of Biological and Agricultural Engineering, 3Cell and Molecular Biology Graduate Program, University of Arkansas, Fayetteville, AR, USA; 4Optical Radiology Laboratory, Department of Radiology, Washington University School of Medicine, St Louis, MO, USAAbstract: Carbon nanotubes (CNTs have recently been in the limelight for their potential role in disease diagnostics and therapeutics, as well as in tissue engineering. Before these medical applications can be realized, there is a need to address issues like opsonization, phagocytosis by macrophages, and sequestration to the liver and spleen for eventual elimination from the body; along with equally important issues such as aqueous solubility, dispersion, biocompatibility, and biofunctionalization. CNTs have not been shown to be able to evade such biological obstacles, which include their nonspecific attachments to cells and other biological components in the bloodstream, before reaching target tissues and cells in vivo. This will eventually determine their longevity in circulation and clearance rate from the body. This review article discusses the current status, challenges, practical strategies, and implementations of coating CNTs with biocompatible and opsonin-resistant moieties, rendering CNTs transparent to opsonins and deceiving the innate immune response to make believe that the CNTs are not foreign. A holistic approach to the development of such "stealth" CNTs is presented, which encompasses not only several biophysicochemical factors that are not limited to surface treatment of CNTs, but also extraneous biological factors such as the protein corona formation that inevitably controls the in vivo fate of the particles. This review also discusses the present and potential applications, along with the future directions, of CNTs and their hybrid

  20. Comparison of the specificity of antibodies to VAR2CSA in Cameroonian multigravidae with and without placental malaria

    DEFF Research Database (Denmark)

    Babakhanyan, Anna; Fang, Rui; Wey, Andrew

    2015-01-01

    BACKGROUND: Antibodies (Ab) to VAR2CSA prevent Plasmodium falciparum-infected erythrocytes from sequestrating in the placenta, i.e., prevent placental malaria (PM). The specificity of Ab to VAR2CSA associated with absence of PM is unknown. Accordingly, differences in the specificity of Ab to VAR2......CSA were compared between multigravidae with and without PM who had Ab to VAR2CSA. METHODS: In a retrospective case-control study, plasma collected from Cameroonian multigravidae with (n = 96) and without (n = 324) PM were screened in 21 assays that measured antibody levels to full length VAR2CSA (FV2......), individual VAR2CSA DBL domains, VAR2CSA domains from different genetic backgrounds (variants), as well as proportion of high avidity Ab to FV2. RESULTS: Multigravidae with and without PM had similar levels of Ab to FV2, the six VAR2CSA DBL domains and different variants, while the proportion of high avidity...

  1. Monoclonal antibody

    International Nuclear Information System (INIS)

    Oyamada, Hiyoshimaru

    1987-01-01

    Some aspects of monoclonal antibodies are described, centering on studies made by the author and those presented at the Second International Conference on Monoclonal Antibody Immunoconjugates for Cancer held in March this year (1987). The history of immuno-nuclear medicine and procedures for producing monoclonal antibodies are briefly outlined. Monoclonal antibodies are immunoglobulins. Here, the structure of IgG, which is used most frequently, is described. An IgG is composed of two antigen binding fragments (Fab) and one crystallizable fragment (Fc). The end portion of a Fab reacts with an antigen. One of the major applications of immuno-nuclear medicine is the diagnosis of cancer. As label nucleides, 131 I and 111 I were selected in most cases in the past while 123 I and 99m Tc are currently used more often. Advantages and disadvantages of this diagnosis method is discussed citing studies presented at the First (1986) and Second (1987) International Conference on Monoclonal Antibody Immunoconjugates for Cancer. The present status of the application of monoclonal antibodies to treatment of cancer is also described. (Nogami, K.)

  2. Assessment of the quality and quantity of naturally induced antibody responses to EBA175RIII-V in Ghanaian children living in two communities with varying malaria transmission patterns

    DEFF Research Database (Denmark)

    Abagna, Hamza B; Acquah, Festus K; Okonu, Ruth

    2018-01-01

    of malaria parasites, which can enhance immune responses against parasite antigens. This study determined the prevalence and relative avidities of naturally induced antibodies to EBA175RIII-VLl in asymptomatic children living in two communities with varying malaria transmission patterns. METHODS: An asexual...... each study site however, children living in Obom had significantly higher EBA175RIII-VLl antibody concentrations than children living in Abura (P 0.05, Mann-Whitney test). Over the course of the study, the relative antibody avidities of EBA175RIII-VLl IgG antibodies were similar within and between......BACKGROUND: Recent global reports on malaria suggest significant decrease in disease severity and an increase in control interventions in many malaria endemic countries, including Ghana. However, a major driving force sustaining malaria transmission in recent times is the asymptomatic carriage...

  3. Epitope specificity is critical for high and moderate avidity cytotoxic T lymphocytes associated with control of viral load and clinical disease in horses with equine infectious anemia virus

    International Nuclear Information System (INIS)

    Mealey, Robert H.; Zhang Baoshan; Leib, Steven R.; Littke, Matt H.; McGuire, Travis C.

    2003-01-01

    Equine infectious anemia virus (EIAV) is a lentivirus that causes persistent infections in horses. We hypothesized that high-avidity CTL specific for nonvariable epitopes might be associated with low viral load and minimal disease in EIAV-infected horses. To test this hypothesis, memory CTL (CTLm) responses were analyzed in two infected horses with high plasma viral loads and recurrent disease (progressors), and in two infected horses with low-to-undetectable viral loads and mild disease (nonprogressors). High-avidity CTLm in one progressor recognized an envelope gp90 epitope, and the data documented for the first time in EIAV that viral variation led to CTL escape. Each of the nonprogressors had high-to-moderate avidity CTLm directed against epitopes within Rev, including the nuclear export and nuclear localization domains. These results suggested that the epitope specificity of high- and moderate-avidity CTLm was an important determinant for disease outcome in the EIAV-infected horses examined

  4. The Influence of Dengue Virus Serotype-2 Infection on Aedes aegypti (Diptera: Culicidae) Motivation and Avidity to Blood Feed

    OpenAIRE

    Maciel-de-Freitas, Rafael; Sylvestre, Gabriel; Gandini, Mariana; Koella, Jacob C.

    2013-01-01

    BACKGROUND: Dengue virus (DENV) is transmitted by Aedes aegypti, a species that lives in close association with human dwellings. The behavior of DENV-infected mosquitoes needs further investigation, especially regarding the potential influence of DENV on mosquito biting motivation and avidity. METHODOLOGY/PRINCIPAL FINDINGS: We orally challenged 4-5 day-old Ae. aegypti females with a low passage DENV serotype -2 (DENV-2) to test whether the virus influences motivation to feed (the likelihood ...

  5. Enhanced change detection performance reveals improved strategy use in avid action video game players.

    Science.gov (United States)

    Clark, Kait; Fleck, Mathias S; Mitroff, Stephen R

    2011-01-01

    Recent research has shown that avid action video game players (VGPs) outperform non-video game players (NVGPs) on a variety of attentional and perceptual tasks. However, it remains unknown exactly why and how such differences arise; while some prior research has demonstrated that VGPs' improvements stem from enhanced basic perceptual processes, other work indicates that they can stem from enhanced attentional control. The current experiment used a change-detection task to explore whether top-down strategies can contribute to VGPs' improved abilities. Participants viewed alternating presentations of an image and a modified version of the image and were tasked with detecting and localizing the changed element. Consistent with prior claims of enhanced perceptual abilities, VGPs were able to detect the changes while requiring less exposure to the change than NVGPs. Further analyses revealed this improved change detection performance may result from altered strategy use; VGPs employed broader search patterns when scanning scenes for potential changes. These results complement prior demonstrations of VGPs' enhanced bottom-up perceptual benefits by providing new evidence of VGPs' potentially enhanced top-down strategic benefits. Copyright © 2010 Elsevier B.V. All rights reserved.

  6. A case report of hyperfunctioning metastatic thyroid cancer and rare I-131 avid liver metastasis

    International Nuclear Information System (INIS)

    Kunawudhi, Anchisa; Promteangtrong, Chetsadaporn; Chotipanich, Chanisa

    2016-01-01

    Thyroid cancer is usually, relatively hypofunctional; most patients with thyroid cancer are clinically euthyroid. The combination of thyroid cancer and thyrotoxicosis is not common. We herein, report a case of follicular thyroid cancer with hyperfunctioning metastasis in a 43-year-old woman who presented with thyrotoxicosis, a cold right thyroid nodule, and low I-131 uptake at the thyroid bed. An additional total body scan with I-131 revealed a large radioiodine avid osteolytic bone metastasis with soft tissue masses and liver metastasis. The patient received treatment with total thyroidectomy, methimazole, and I-131 at a cumulative dose of 600 mCi along with recombinant human thyroid-stimulating hormone before the first I-131 treatment and palliative radiation. The patient had normal liver function test and experienced a mild degree of bone marrow suppression after I-131. At the 2-year follow-up, the patient was still alive with the progression of bone metastases but was doing well with less severe thyrotoxicosis, good ambulation, and an Eastern Cooperative Oncology Group performance status of 2. Clinicians should be aware of the unusual concurrent presentation of thyrotoxicosis and thyroid cancer, a differential diagnosis in patients with thyrotoxicosis and low or normal radioiodine uptake over the neck and also potential pitfalls during radionuclide treatment

  7. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus

    Science.gov (United States)

    Liao, Hua-Xin; Lynch, Rebecca; Zhou, Tongqing; Gao, Feng; Alam, S. Munir; Boyd, Scott D.; Fire, Andrew Z.; Roskin, Krishna M.; Schramm, Chaim A.; Zhang, Zhenhai; Zhu, Jiang; Shapiro, Lawrence; Mullikin, James C.; Gnanakaran, S.; Hraber, Peter; Wiehe, Kevin; Kelsoe, Garnett; Yang, Guang; Xia, Shi-Mao; Montefiori, David C.; Parks, Robert; Lloyd, Krissey E.; Scearce, Richard M.; Soderberg, Kelly A.; Cohen, Myron; Kaminga, Gift; Louder, Mark K.; Tran, Lillan M.; Chen, Yue; Cai, Fangping; Chen, Sheri; Moquin, Stephanie; Du, Xiulian; Joyce, Gordon M.; Srivatsan, Sanjay; Zhang, Baoshan; Zheng, Anqi; Shaw, George M.; Hahn, Beatrice H.; Kepler, Thomas B.; Korber, Bette T.M.; Kwong, Peter D.; Mascola, John R.; Haynes, Barton F.

    2013-01-01

    Current HIV-1 vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in ~20% of HIV-1-infected individuals, and details of their generation could provide a roadmap for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from time of infection. The mature antibody, CH103, neutralized ~55% of HIV-1 isolates, and its co-crystal structure with gp120 revealed a novel loop-based mechanism of CD4-binding site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the CH103-lineage unmutated common ancestor avidly bound the transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody neutralization breadth was preceded by extensive viral diversification in and near the CH103 epitope. These data elucidate the viral and antibody evolution leading to induction of a lineage of HIV-1 broadly neutralizing antibodies and provide insights into strategies to elicit similar antibodies via vaccination. PMID:23552890

  8. Catalytic Antibodies

    Indian Academy of Sciences (India)

    biological processes and is intended to catalyze a reaction for which no real enzyme is ... the reaction. In order to enhance the rates of chemical reactions, enzymes, ..... of such antibodies has already been exploited in the production of a biosensor. ..... tant to the pharmaceutical and fine chemical industries for the synthesis ...

  9. Evading the top-quark mass bound at the Fermilab Tevatron: New signals for the top quark

    International Nuclear Information System (INIS)

    Mukhopadhyaya, B.; Nandi, S.

    1991-01-01

    If an SU(2)-singlet charge-2/3 quark exists, current data allow a wide range for the parameters of the 4x4 mixing matrix in which the usual ''hard-lepton'' signal of the top quark is suppressed. For a light Higgs boson, the top quark decays predominantly via the flavor-changing Yukawa interaction, thus evading the Fermilab Tevatron bounds on its mass. For a heavier Higgs boson, flavor-changing neutral-current decays become important, giving rise to anomalous Z-pair production, testable at the upgraded Tevetron, at the CERN Large Hardon Collider, and at the Superconducting Super Collider

  10. Electrical storm presages nonsudden death: the antiarrhythmics versus implantable defibrillators (AVID) trial.

    Science.gov (United States)

    Exner, D V; Pinski, S L; Wyse, D G; Renfroe, E G; Follmann, D; Gold, M; Beckman, K J; Coromilas, J; Lancaster, S; Hallstrom, A P

    2001-04-24

    Electrical storm, multiple temporally related episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF), is a frequent problem among recipients of implantable cardioverter defibrillators (ICDs). However, insufficient data exist regarding its prognostic significance. This analysis includes 457 patients who received an ICD in the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial and who were followed for 31 +/- 13 months. Electrical storm was defined as > or = 3 separate episodes of VT/VF within 24 hours. Characteristics and survival of patients surviving electrical storm (n = 90), those with VT/VF unrelated to electrical storm (n = 184), and the remaining patients (n = 183) were compared. The 3 groups differed in terms of ejection fraction, index arrhythmia, revascularization status, and baseline medication use. Survival was evaluated using time-dependent Cox modeling. Electrical storm occurred 9.2 +/- 11.5 months after ICD implantation, and most episodes (86%) were due to VT. Electrical storm was a significant risk factor for subsequent death, independent of ejection fraction and other prognostic variables (relative risk [RR], 2.4; 95% confidence interval [CI], 1.3 to 4.2; P = 0.003), but VT/VF unrelated to electrical storm was not (RR, 1.0; 95% CI, 0.6 to 1.7; P = 0.9). The risk of death was greatest 3 months after electrical storm (RR, 5.4; 95% Cl, 2.4 to 12.3; P = 0.0001) and diminished beyond this time (RR, 1.9; 95% CI, 1.0 to 3.6; P=0.04). Electrical storm is an important, independent marker for subsequent death among ICD recipients, particularly in the first 3 months after its occurrence. However, the development of VT/VF unrelated to electrical storm does not seem to be associated with an increased risk of subsequent death.

  11. Dual time point FDG PET imaging in evaluating pulmonary nodules with low FDG avidity

    International Nuclear Information System (INIS)

    Chen Xiang; Zhao Jinhua; Song Jianhua; Xing Yan; Wang Taisong; Qiao Wenli

    2010-01-01

    A standardized uptake value (SUV) of 2.5 is frequently used as criteria to evaluate pulmonary lesions. However, false results may occur. Some studies have shown the usefulness of delayed PET for improving accuracy, while others recently have shown fewer promising results. This study was designed to investigate the accuracy of dual time point (DTP) FDG PET imaging in the evaluation of pulmonary lesions with an initial SUV less than 2.5. DTP FDG PET studies were conducted about 1 and 2 hours after FDG injection, and pulmonary lesions with an initial SUV less than 2.5 were identified. Nodules with pathologic results or imaging follow up were included. The differences in SUV and retention index (RI) between benign and malignant pulmonary lesions were analyzed. Receiver operating characteristics (ROC) analysis was performed to evaluate the discriminating validity of SUV and RI. 51 lesions were finally included. A RI greater than 0% was observed in 64% of the benign lesions; 56% had a RI greater than 10%. Among the malignancies, 80.8% had a RI greater than 0%, and 61.5% had a RI greater than 10%. We found no significant differences in SUV and RI between benign and malignant lesions. The area under the ROC curve did not differ from 0.5 whether using SUV or the retention index. Utilizing a SUV increase of 10%, the sensitivity was 61.5%, specificity 44% and accuracy was 52.9%. Dual time point FDG PET may not be of benefit in the evaluation of pulmonary nodules with low FDG avidity. (authors)

  12. Anti-protein C antibodies are associated with resistance to endogenous protein C activation and a severe thrombotic phenotype in antiphospholipid syndrome.

    Science.gov (United States)

    Arachchillage, D R J; Efthymiou, M; Mackie, I J; Lawrie, A S; Machin, S J; Cohen, H

    2014-11-01

    Antiphospholipid antibodies may interfere with the anticoagulant activity of activated protein C (APC) to induce acquired APC resistance (APCr). To investigate the frequency and characteristics of APCr by using recombinant human APC (rhAPC) and endogenous protein C activation in antiphospholipid syndrome (APS). APCr was assessed in APS and non-APS venous thromboembolism (VTE) patients on warfarin and normal controls with rhAPC or Protac by thrombin generation. IgG anti-protein C and anti-protein S antibodies and avidity were assessed by ELISA. APS patients showed greater resistance to both rhAPC and Protac than non-APS patients and normal controls (median normalized endogenous thrombin potential inhibition): APS patients with rhAPC, 81.3% (95% confidence interval [CI] 75.2-88.3%; non-APS patients with rhAPC, 97.7% (95% CI 93.6-101.8%; APS patients with Protac, 66.0% (95% CI 59.5-72.6%); and non-APS patients with Protac, 80.7 (95% CI 74.2-87.2%). APS patients also had a higher frequency and higher levels of anti-protein C antibodies, with 60% (15/25) high-avidity antibodies. High-avidity anti-protein C antibodies were associated with greater APCr and with a severe thrombotic phenotype (defined as the development of recurrent VTE while patients were receiving therapeutic anticoagulation or both venous and arterial thrombosis). Twelve of 15 (80%) patients with high-avidity anti-protein C antibodies were classified as APS category I. Thrombotic APS patients showed greater APCr to both rhAPC and activation of endogenous protein C by Protac. High-avidity anti-protein C antibodies, associated with greater APCr, may provide a marker for a severe thrombotic phenotype in APS. However, in patients with category I APS, it remains to be established whether anti-protein C or anti-β2 -glycoprotein I antibodies are responsible for APCr. © 2014 International Society on Thrombosis and Haemostasis.

  13. Antiparietal cell antibody test

    Science.gov (United States)

    APCA; Anti-gastric parietal cell antibody; Atrophic gastritis - anti-gastric parietal cell antibody; Gastric ulcer - anti-gastric parietal cell antibody; Pernicious anemia - anti-gastric parietal cell antibody; ...

  14. Radiation Therapy to the Primary and Postinduction Chemotherapy MIBG-Avid Sites in High-Risk Neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Mazloom, Ali; Louis, Chrystal U.; Nuchtern, Jed; Kim, Eugene; Russell, Heidi; Allen-Rhoades, Wendy; Krance, Robert; Paulino, Arnold C., E-mail: apaulino@mdanderson.org

    2014-11-15

    Purpose: Although it is generally accepted that consolidation therapy for neuroblastoma includes irradiation of the primary site and any remaining metaiodobenzylguanidine (MIBG)-avid metastatic sites, limited information has been published regarding the efficacy of this approach. Methods and Materials: Thirty patients with high-risk neuroblastoma were treated at 1 radiation therapy (RT) department after receiving 5 cycles of induction chemotherapy and resection. All patients had at least a partial response after induction therapy, based upon international neuroblastoma response criteria. The primary sites were treated with 24 to 30 Gy whereas the MIBG-avid metastatic sites were treated with 24 Gy. RT was followed by high-dose chemotherapy with autologous stem cell rescue and 6 months of cis-retinoic acid. Results: The 5-year progression-free survival (PFS) and overall survival (OS) rates were 48% and 59%, respectively. The 5-year locoregional control at the primary site was 84%. There were no differences in locoregional control according to degree of primary surgical resection. The 5-year local control rate for metastatic sites was 74%. The 5-year PFS rates for patients with 0, 1, 2, and >3 postinduction MIBG sites were 66%, 57%, 20%, and 0% (P<.0001), respectively, whereas 5-year OS rates were 80%, 57%, 50%, and 0%, respectively (P<.0001). Conclusions: RT to the primary site and postinduction MIBG-positive metastatic sites was associated with 84% and 74% local control, respectively. The number of MIBG-avid sites present after induction chemotherapy and surgery was predictive of progression-free and overall survival.

  15. Contribution of IgG avidity and PCR for the early diagnosis of ...

    African Journals Online (AJOL)

    2017-09-03

    Sep 3, 2017 ... Laboratory of Cellular Toxicology, Faculty of Sciences, University of Badji Mokhtar, Annaba, Algeria. 3. ... agnosis is difficult, especially when serological testing for IgG/IgM antibodies fail to differentiate between a recent and a past infection. In this ...... S, Wallace P, Peyron F. Multicenter proficiency study for.

  16. Work in progress. Gastrointestinal ulcerations: detection using a technetium-99m-labeled ulcer-avid agent

    International Nuclear Information System (INIS)

    Vasquez, T.E.; Bridges, R.L.; Braunstein, P.; Jansholt, A.L.; Meshkinpour, H.

    1983-01-01

    Technetium-99m-labeled sucralfate, an ulcer-avid material, was shown in preliminary animal and human studies to be stable in vivo with good sensitivity. Eight experimentally produced discrete gastric ulcers in three rabbits were visualized using this material. Of seven human studies, four studies were true-positive and three were true-negative. It is suggested that Tc-99m-labeled sucralfate may prove to have significant clinical advantages for the evaluation of gastrointestinal ulcer disease and other diseases that are associated with loss of mucosal integrity. The method for labeling sucralfate with Tc-99m was developed by the authors

  17. FDG-avid portal vein tumor thrombosis from hepatocellular carcinoma in contrast-enhanced FDG PET/CT

    Directory of Open Access Journals (Sweden)

    Canh Nguyen

    2015-01-01

    Full Text Available Objective(s: In this study, we aimed to describe the characteristics of portal vein tumor thrombosis (PVTT, complicating hepatocellular carcinoma (HCC in contrast-enhanced FDG PET/CT scan. Methods: In this retrospective study, 9 HCC patients with FDG-avid PVTT were diagnosed by contrast-enhanced fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT, which is a combination of dynamic liver CT scan, multiphase imaging, and whole-body PET scan. PET and CT DICOM images of patients were imported into the PET/CT imaging system for the re-analysis of contrast enhancement and FDG uptake in thrombus, the diameter of the involved portal vein, and characteristics of liver tumors and metastasis. Results: Two patients with previously untreated HCC and 7 cases with previously treated HCC had FDG-avid PVTT in contrast-enhanced FDG PET/CT scan. During the arterial phase of CT scan, portal vein thrombus showed contrast enhancement in 8 out of 9 patients (88.9%. PET scan showed an increased linear FDG uptake along the thrombosed portal vein in all patients. The mean greatest diameter of thrombosed portal veins was 1.8 ± 0.2 cm, which was significantly greater than that observed in normal portal veins (P<0.001. FDG uptake level in portal vein thrombus was significantly higher than that of blood pool in the reference normal portal vein (P=0.001. PVTT was caused by the direct extension of liver tumors. All patients had visible FDG-avid liver tumors in contrast-enhanced images. Five out of 9 patients (55.6% had no extrahepatic metastasis, 3 cases (33.3% had metastasis of regional lymph nodes, and 1 case (11.1% presented with distant metastasis. The median estimated survival time of patients was 5 months. Conclusion: The intraluminal filling defect consistent with thrombous within the portal vein, expansion of the involved portal vein, contrast enhancement, and linear increased FDG uptake of the thrombus extended from liver tumor are

  18. The Importance of IgG Avidity and the Polymerase Chain Reaction in Treating Toxoplasmosis during Pregnancy: Current Knowledge

    Directory of Open Access Journals (Sweden)

    João Bortoletti Filho

    2013-01-01

    Full Text Available A brief report on the nature and epidemiology of T. gondii infection is firstly presented. The importance of the specific IgG avidity test and polymerase chain reaction (PCR for toxoplasmosis is discussed, along with their significance and importance as auxiliary methods for determining the most likely time for the initial infection by this coccidian and for defining the therapeutic strategy. Lastly, practical comments are made in relation to the classical therapeutic regimens, with special attention to the indications for fetal treatment, when this is necessary.

  19. Antibody Engineering and Therapeutics

    Science.gov (United States)

    Almagro, Juan Carlos; Gilliland, Gary L; Breden, Felix; Scott, Jamie K; Sok, Devin; Pauthner, Matthias; Reichert, Janice M; Helguera, Gustavo; Andrabi, Raiees; Mabry, Robert; Bléry, Mathieu; Voss, James E; Laurén, Juha; Abuqayyas, Lubna; Barghorn, Stefan; Ben-Jacob, Eshel; Crowe, James E; Huston, James S; Johnston, Stephen Albert; Krauland, Eric; Lund-Johansen, Fridtjof; Marasco, Wayne A; Parren, Paul WHI; Xu, Kai Y

    2014-01-01

    The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates. PMID:24589717

  20. First preclinical evaluation of mono-[{sup 123}I]iodohypericin as a necrosis-avid tracer agent

    Energy Technology Data Exchange (ETDEWEB)

    Ni, Yicheng; Chen, Feng; Marchal, Guy [University Hospital Gasthuisberg, Department of Radiology, Leuven (Belgium); Huyghe, Dieter; Verbeke, Kristin; Verbruggen, Alfons M.; Bormans, Guy M. [University of Leuven, Laboratory of Radiopharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Leuven (Belgium); Witte, Peter A. de [University of Leuven, Laboratory of Pharmaceutical Biology and Phytopharmacology, Faculty of Pharmaceutical Sciences, Leuven (Belgium); Nuyts, Johan; Mortelmans, Luc [University Hospital Gasthuisberg, Department of Nuclear Medicine, Leuven (Belgium)

    2006-05-15

    We have labelled hypericin, a polyphenolic polycyclic quinone found in St. John's wort (Hypericum perforatum), with{sup 123}I and evaluated mono-[{sup 123}I]iodohypericin (MIH) as a potential necrosis-avid diagnostic tracer agent. MIH was prepared by an electrophilic radioiodination method. The new tracer agent was evaluated in animal models of liver infarction in the rat and heart infarction in the rabbit using single-photon emission computed tomography (SPECT), triphenyltetrazolium chloride (TTC) histochemical staining, serial sectional autoradiography and microscopy, and radioactivity counting techniques. Using in vivo SPECT imaging, hepatic and cardiac infarctions were persistently visualised as well-defined hot spots over 48 h. Preferential uptake of the tracer agent in necrotic tissue was confirmed by perfect match of images from post-mortem TTC staining, autoradiography (ARX) and histology. Radioactivity concentration in infarcted tissues was over 10 times (liver; 3.51% ID/g in necrotic tissue vs 0.38% ID/g in normal tissue at 60 h p.i.) and over 6 times (myocardium; 0.36% ID/g in necrotic tissue vs 0.054% ID/g in normal tissue; ratios up to 18 for selected parts on ARX images) higher than in normal tissues. The results suggest that hypericin derivatives may serve as powerful necrosis-avid diagnostic agents for assessment of tissue viability. (orig.)

  1. Differential expression profiling of circulation microRNAs in PTC patients with non-131I and 131I-avid lungs metastases: a pilot study

    International Nuclear Information System (INIS)

    Qiu, Zhong-Ling; Shen, Chen-Tian; Song, Hong-Jun; Wei, Wei-Jun; Luo, Quan-Yong

    2015-01-01

    Introduction: Loss of the ability to concentrate 131 I is one of the important causes of radioiodine-refractory disease in papillary thyroid carcinoma (PTC). Recent advantages of serum microRNAs (miRNAs) open a new realm of possibilities for noninvasive diagnosis and prognosis of many cancers. The aim of the current study was to identify differential expression profiling of circulation miRNAs in PTC patients with non- 131 I and 131 I-avid lungs metastases. Methods: The expressions of miRNAs were examined using miRNA microarray chip. The most significantly changed miRNAs from microarray were verified by using qRT-PCR. The potential miRNAs regulating target genes and their preliminary biological functions were forecasted by Bioinformatic analysis. Results: Compared to 131 I-avid lung metastases, 13 kinds of significantly differential serum miRNAs including 5 upregulated miRNAs (miR-1249, miR-106a, miR-503, miR-34c-5p, miR-1281) and 8 downregulated miRNAs (miR-1915, miR-2861, miR-3196, miR-500, miR-572, miR-33b, miR-554, miR-18a) in PTC patients with non- 131 I-avid lung metastases were identified. Bioinformatic analysis demonstrated that miR-106a was the core miRNA regulating 193 genes in the network. The results of validation confirmed the up-regulation of miR-106a in non- 131 I-avid lungs metastatic PTC patients. Conclusion: Differentially expressed serum miRNA profiles between PTC patients with non- 131 I and 131 I-avid lungs metastases were analyzed. These findings in our present study could represent new clues for the diagnostic and therapeutic strategy in PTC patients with non- 131 I-avid metastatic disease

  2. Human Cell Line-Derived Monoclonal IgA Antibodies for Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Felix Hart

    2017-05-01

    Full Text Available IgA antibodies have great potential to improve the functional diversity of current IgG antibody-based cancer immunotherapy options. However, IgA production and purification is not well established, which can at least in part be attributed to the more complex glycosylation as compared to IgG antibodies. IgA antibodies possess up to five N-glycosylation sites within their constant region of the heavy chain as compared to one site for IgG antibodies. The human GlycoExpress expression system was developed to produce biotherapeutics with optimized glycosylation and used here to generate a panel of IgA isotype antibodies directed against targets for solid (TA-mucin 1, Her2, EGFR, Thomsen–Friedenreich and hematological (CD20 cancer indications. The feasibility of good manufacturing practice was shown by the production of 11 g IgA within 35 days in a one liter perfusion bioreactor, and IgA antibodies in high purity were obtained after purification. The monoclonal IgA antibodies possessed a high sialylation degree, and no non-human glycan structures were detected. Kinetic analysis revealed increased avidity antigen binding for IgA dimers as compared to monomeric antibodies. The IgA antibodies exhibited potent Fab- and Fc-mediated functionalities against cancer cell lines, whereby especially granulocytes are recruited. Therefore, for patients who do not sufficiently benefit from therapeutic IgG antibodies, IgA antibodies may complement current regiment options and represent a promising strategy for cancer immunotherapy. In conclusion, a panel of novel biofunctional IgA antibodies with human glycosylation was successfully generated.

  3. An improved haemolytic plaque assay for the detection of cells secreting antibody to bacterial antigens

    DEFF Research Database (Denmark)

    Barington, T; Heilmann, C

    1992-01-01

    Recent advances in the development of conjugate polysaccharide vaccines for human use have stimulated interest in the use of assays detecting antibody-secreting cells (AbSC) with specificity for bacterial antigens. Here we present improved haemolytic plaque-forming cell (PFC) assays detecting Ab......SC with specificity for tetanus and diphtheria toxoid as well as for Haemophilus influenzae type b and pneumococcal capsular polysaccharides. These assays were found to be less time consuming, more economical and yielded 1.9-3.4-fold higher plaque numbers than traditional Jerne-type PFC assays. In the case of anti......-polysaccharide antibodies aggregation of secreted monomeric antibody (IgG) is critical for plaque formation and increases the avidity of binding to target cells....

  4. Anopheles Midgut Epithelium Evades Human Complement Activity by Capturing Factor H from the Blood Meal

    Science.gov (United States)

    Khattab, Ayman; Barroso, Marta; Miettinen, Tiera; Meri, Seppo

    2015-01-01

    Hematophagous vectors strictly require ingesting blood from their hosts to complete their life cycles. Exposure of the alimentary canal of these vectors to the host immune effectors necessitates efficient counteractive measures by hematophagous vectors. The Anopheles mosquito transmitting the malaria parasite is an example of hematophagous vectors that within seconds can ingest human blood double its weight. The innate immune defense mechanisms, like the complement system, in the human blood should thereby immediately react against foreign cells in the mosquito midgut. A prerequisite for complement activation is that the target cells lack complement regulators on their surfaces. In this work, we analyzed whether human complement is active in the mosquito midgut, and how the mosquito midgut cells protect themselves against complement attack. We found that complement remained active for a considerable time and was able to kill microbes within the mosquito midgut. However, the Anopheles mosquito midgut cells were not injured. These cells were found to protect themselves by capturing factor H, the main soluble inhibitor of the alternative complement pathway. Factor H inhibited complement on the midgut cells by promoting inactivation of C3b to iC3b and preventing the activity of the alternative pathway amplification C3 convertase enzyme. An interference of the FH regulatory activity by monoclonal antibodies, carried to the midgut via blood, resulted in increased mosquito mortality and reduced fecundity. By using a ligand blotting assay, a putative mosquito midgut FH receptor could be detected. Thereby, we have identified a novel mechanism whereby mosquitoes can tolerate human blood. PMID:25679788

  5. Anopheles midgut epithelium evades human complement activity by capturing factor H from the blood meal.

    Directory of Open Access Journals (Sweden)

    Ayman Khattab

    2015-02-01

    Full Text Available Hematophagous vectors strictly require ingesting blood from their hosts to complete their life cycles. Exposure of the alimentary canal of these vectors to the host immune effectors necessitates efficient counteractive measures by hematophagous vectors. The Anopheles mosquito transmitting the malaria parasite is an example of hematophagous vectors that within seconds can ingest human blood double its weight. The innate immune defense mechanisms, like the complement system, in the human blood should thereby immediately react against foreign cells in the mosquito midgut. A prerequisite for complement activation is that the target cells lack complement regulators on their surfaces. In this work, we analyzed whether human complement is active in the mosquito midgut, and how the mosquito midgut cells protect themselves against complement attack. We found that complement remained active for a considerable time and was able to kill microbes within the mosquito midgut. However, the Anopheles mosquito midgut cells were not injured. These cells were found to protect themselves by capturing factor H, the main soluble inhibitor of the alternative complement pathway. Factor H inhibited complement on the midgut cells by promoting inactivation of C3b to iC3b and preventing the activity of the alternative pathway amplification C3 convertase enzyme. An interference of the FH regulatory activity by monoclonal antibodies, carried to the midgut via blood, resulted in increased mosquito mortality and reduced fecundity. By using a ligand blotting assay, a putative mosquito midgut FH receptor could be detected. Thereby, we have identified a novel mechanism whereby mosquitoes can tolerate human blood.

  6. Immunoglobulin G Avidities in Infants in Mexico after Primary Immunization with Three Doses of Polyribosylribitol Phosphate-Tetanus Toxoid Haemophilus influenzae Type b Vaccine▿ †

    Science.gov (United States)

    Gómez-de-León, Patricia; Díaz-García, F. Javier; Villaseñor-Sierra, Alberto; Segura, Jorge; Carranza, Martha I.; Arredondo-Garcia, José Luis; Santos, José Ignacio

    2008-01-01

    Serum immunoglobulin G concentrations and avidities specific to Haemophilus influenzae type b (Hib) were measured in 208 children living in Guadalajara and Mexico City. Protective concentrations were found in 98.9% and 100.0% of participants, respectively. Geometric mean concentrations differed between both populations and/or among age groups. Mean avidities differed only among the 7- to 12-month-old children. Diphtheria-tetanus-whole-cell pertussis-hepatitis B-Hib primary vaccination seems to induce protection in Mexican children. PMID:18417667

  7. Immunoglobulin G avidities in infants in Mexico after primary immunization with three doses of polyribosylribitol phosphate-tetanus toxoid Haemophilus influenzae type b vaccine.

    Science.gov (United States)

    Gómez-de-León, Patricia; Díaz-García, F Javier; Villaseñor-Sierra, Alberto; Segura, Jorge; Carranza, Martha I; Arredondo-Garcia, José Luis; Santos, José Ignacio

    2008-06-01

    Serum immunoglobulin G concentrations and avidities specific to Haemophilus influenzae type b (Hib) were measured in 208 children living in Guadalajara and Mexico City. Protective concentrations were found in 98.9% and 100.0% of participants, respectively. Geometric mean concentrations differed between both populations and/or among age groups. Mean avidities differed only among the 7- to 12-month-old children. Diphtheria-tetanus-whole-cell pertussis-hepatitis B-Hib primary vaccination seems to induce protection in Mexican children.

  8. Conformational Occlusion of Blockade Antibody Epitopes, a Novel Mechanism of GII.4 Human Norovirus Immune Evasion.

    Science.gov (United States)

    Lindesmith, Lisa C; Mallory, Michael L; Debbink, Kari; Donaldson, Eric F; Brewer-Jensen, Paul D; Swann, Excel W; Sheahan, Timothy P; Graham, Rachel L; Beltramello, Martina; Corti, Davide; Lanzavecchia, Antonio; Baric, Ralph S

    2018-01-01

    Extensive antigenic diversity within the GII.4 genotype of human norovirus is a major driver of pandemic emergence and a significant obstacle to development of cross-protective immunity after natural infection and vaccination. However, human and mouse monoclonal antibody studies indicate that, although rare, antibodies to conserved GII.4 blockade epitopes are generated. The mechanisms by which these epitopes evade immune surveillance are uncertain. Here, we developed a new approach for identifying conserved GII.4 norovirus epitopes. Utilizing a unique set of virus-like particles (VLPs) representing the in vivo -evolved sequence diversity within an immunocompromised person, we identify key residues within epitope F, a conserved GII.4 blockade antibody epitope. The residues critical for antibody binding are proximal to evolving blockade epitope E. Like epitope F, antibody blockade of epitope E was temperature sensitive, indicating that particle conformation regulates antibody access not only to the conserved GII.4 blockade epitope F but also to the evolving epitope E. These data highlight novel GII.4 mechanisms to protect blockade antibody epitopes, map essential residues of a GII.4 conserved epitope, and expand our understanding of how viral particle dynamics may drive antigenicity and antibody-mediated protection by effectively shielding blockade epitopes. Our data support the notion that GII.4 particle breathing may well represent a major mechanism of humoral immune evasion supporting cyclic pandemic virus persistence and spread in human populations. IMPORTANCE In this study, we use norovirus virus-like particles to identify key residues of a conserved GII.4 blockade antibody epitope. Further, we identify an additional GII.4 blockade antibody epitope to be occluded, with antibody access governed by temperature and particle dynamics. These findings provide additional support for particle conformation-based presentation of binding residues mediated by a particle

  9. Influence of intermittent preventive treatment on antibodies to VAR2CSA in pregnant Cameroonian women

    DEFF Research Database (Denmark)

    Babakhanyan, Anna; Tutterrow, Yeung L; Bobbili, Naveen

    2016-01-01

    Intermittent preventive treatment (IPT) and insecticide-treated bed nets are the standard of care for preventing malaria in pregnant women. Since these preventive measures reduce exposure to malaria, their influence on the antibody (Ab) response to the parasite antigen VAR2CSA was evaluated...... in pregnant Cameroonian women exposed to holoendemic malaria. Ab levels to full-length VAR2CSA (FV2), variants of the six Duffy binding like (DBL) domains, and proportion of high avidity Ab to FV2 were measured longitudinally in 92 women before and 147 women after IPT. As predicted, reduced exposure...

  10. The effect of high antigen density on solid-phase radioimmunoassays for antibody regardless of immunoglobulin class

    International Nuclear Information System (INIS)

    Rubin, R.L.; Hardtke, M.A.; Carr, R.I.

    1980-01-01

    Human sera containing antibody to casein or to bovine serum albumin were used to assess the validity and utility of a solid-phase assay for quantitating antibody activity. Rabbit anti-human immunoglobulin radiolabeled with 125 I and capable of reacting with all human immunoglobulin classes was used to detect antibody bound to antigen immobilized to polystyrene tubes by a new covalent technique. This method results in very high antigen concentrations in highly stable association with polystyrene tubes. Kinetic and absorption studies demonstrated that low avidity antibodies are better detected when antigen is immobilized by the covalent method than when passively adsorbed. Conditions are described for minimizing artifactual interactions and for obtaining results similar to those obtained with conventional, liquid-phase assays. Failure to reach equilibrium in solid-phase assays and other problems are proposed to explain, in part, the inability to obtain a better correlation between solid- and liquid-phase immunoassays. (Auth.)

  11. Enhanced antibody-dependent cellular phagocytosis by chimeric monoclonal antibodies with tandemly repeated Fc domains.

    Science.gov (United States)

    Nagashima, Hiroaki; Ootsubo, Michiko; Fukazawa, Mizuki; Motoi, Sotaro; Konakahara, Shu; Masuho, Yasuhiko

    2011-04-01

    We previously reported that chimeric monoclonal antibodies (mAbs) with tandemly repeated Fc domains, which were developed by introducing tandem repeats of Fc domains downstream of 2 Fab domains, augmented binding avidities for all Fcγ receptors, resulting in enhanced antibody (Ab)-dependent cellular cytotoxicity. Here we investigated regarding Ab-dependent cellular phagocytosis (ADCP) mediated by these chimeric mAbs, which is considered one of the most important mechanisms that kills tumor cells, using two-color flow cytometric methods. ADCP mediated by T3-Ab, a chimeric mAb with 3 tandemly repeated Fc domains, was 5 times more potent than that by native anti-CD20 M-Ab (M-Ab hereafter). Furthermore, T3-Ab-mediated ADCP was resistant to competitive inhibition by intravenous Ig (IVIG), although M-Ab-mediated ADCP decreased in the presence of IVIG. An Fcγ receptor-blocking study demonstrated that T3-Ab mediated ADCP via both FcγRIA and FcγRIIA, whereas M-Ab mediated ADCP exclusively via FcγRIA. These results suggest that chimeric mAbs with tandemly repeated Fc domains enhance ADCP as well as ADCC, and that Fc multimerization may significantly enhance the efficacy of therapeutic Abs. Copyright © 2010 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  12. Muusikamaailm : Arvo Pärdi uus teos. Telemanni päevad Magdeburgis. Uus orkester Soomes. Ingvar Lidholm 80. Auhindu ja preemiaid / Priit Kuusk

    Index Scriptorium Estoniae

    Kuusk, Priit, 1938-

    2001-01-01

    21. veebr. tuli Oxfordis maailmaesiettekandele A. Pärdi teos "Littlemore Tractus". Telemanni päevade raames toimuvast rahvusvahelisest kammeransamblite konkursist Magdeburgis. O. Mustonen asutas Helsingis uue orkestri. Lühidalt I.Lidholmi tegevusest ja loomingust. P. Norgaardile ja H. von Manen'ile antud autasust ja preemiast

  13. Muusikamaailm : Festivalil Schwetzingenis. Ellingtoni sajandi tähistamine. Linz saab uue ooperimaja. Isaac Stern viiulita Saksamaal. Muusikapäevad Luksemburgis / Priit Kuusk

    Index Scriptorium Estoniae

    Kuusk, Priit, 1938-

    1999-01-01

    30. apr.-7. juunini toimuvast muusikafestivalist Schwetzingenis. D. Ellingtoni 100. sünniaastapäeva tähistamisest maailmas. Valmis Linzi uue ooperimaja planeering. I. Stern juhatas kümnepäevast seminari Kölni Kõrgema Muusikakooli juures. Rahvusvahelise Nüüdismuusika Ühingu (ISCM) iga-aastased maailma muusikapäevad toimuvad 2000. aastal Luksemburgis

  14. Recalibration of the limiting antigen avidity EIA to determine mean duration of recent infection in divergent HIV-1 subtypes.

    Directory of Open Access Journals (Sweden)

    Yen T Duong

    Full Text Available Mean duration of recent infection (MDRI and misclassification of long-term HIV-1 infections, as proportion false recent (PFR, are critical parameters for laboratory-based assays for estimating HIV-1 incidence. Recent review of the data by us and others indicated that MDRI of LAg-Avidity EIA estimated previously required recalibration. We present here results of recalibration efforts using >250 seroconversion panels and multiple statistical methods to ensure accuracy and consensus.A total of 2737 longitudinal specimens collected from 259 seroconverting individuals infected with diverse HIV-1 subtypes were tested with the LAg-Avidity EIA as previously described. Data were analyzed for determination of MDRI at ODn cutoffs of 1.0 to 2.0 using 7 statistical approaches and sub-analyzed by HIV-1 subtypes. In addition, 3740 specimens from individuals with infection >1 year, including 488 from patients with AIDS, were tested for PFR at varying cutoffs.Using different statistical methods, MDRI values ranged from 88-94 days at cutoff ODn = 1.0 to 177-183 days at ODn = 2.0. The MDRI values were similar by different methods suggesting coherence of different approaches. Testing for misclassification among long-term infections indicated that overall PFRs were 0.6% to 2.5% at increasing cutoffs of 1.0 to 2.0, respectively. Balancing the need for a longer MDRI and smaller PFR (<2.0% suggests that a cutoff ODn = 1.5, corresponding to an MDRI of 130 days should be used for cross-sectional application. The MDRI varied among subtypes from 109 days (subtype A&D to 152 days (subtype C.Based on the new data and revised analysis, we recommend an ODn cutoff = 1.5 to classify recent and long-term infections, corresponding to an MDRI of 130 days (118-142. Determination of revised parameters for estimation of HIV-1 incidence should facilitate application of the LAg-Avidity EIA for worldwide use.

  15. Recalibration of the limiting antigen avidity EIA to determine mean duration of recent infection in divergent HIV-1 subtypes.

    Science.gov (United States)

    Duong, Yen T; Kassanjee, Reshma; Welte, Alex; Morgan, Meade; De, Anindya; Dobbs, Trudy; Rottinghaus, Erin; Nkengasong, John; Curlin, Marcel E; Kittinunvorakoon, Chonticha; Raengsakulrach, Boonyos; Martin, Michael; Choopanya, Kachit; Vanichseni, Suphak; Jiang, Yan; Qiu, Maofeng; Yu, Haiying; Hao, Yan; Shah, Neha; Le, Linh-Vi; Kim, Andrea A; Nguyen, Tuan Anh; Ampofo, William; Parekh, Bharat S

    2015-01-01

    Mean duration of recent infection (MDRI) and misclassification of long-term HIV-1 infections, as proportion false recent (PFR), are critical parameters for laboratory-based assays for estimating HIV-1 incidence. Recent review of the data by us and others indicated that MDRI of LAg-Avidity EIA estimated previously required recalibration. We present here results of recalibration efforts using >250 seroconversion panels and multiple statistical methods to ensure accuracy and consensus. A total of 2737 longitudinal specimens collected from 259 seroconverting individuals infected with diverse HIV-1 subtypes were tested with the LAg-Avidity EIA as previously described. Data were analyzed for determination of MDRI at ODn cutoffs of 1.0 to 2.0 using 7 statistical approaches and sub-analyzed by HIV-1 subtypes. In addition, 3740 specimens from individuals with infection >1 year, including 488 from patients with AIDS, were tested for PFR at varying cutoffs. Using different statistical methods, MDRI values ranged from 88-94 days at cutoff ODn = 1.0 to 177-183 days at ODn = 2.0. The MDRI values were similar by different methods suggesting coherence of different approaches. Testing for misclassification among long-term infections indicated that overall PFRs were 0.6% to 2.5% at increasing cutoffs of 1.0 to 2.0, respectively. Balancing the need for a longer MDRI and smaller PFR (<2.0%) suggests that a cutoff ODn = 1.5, corresponding to an MDRI of 130 days should be used for cross-sectional application. The MDRI varied among subtypes from 109 days (subtype A&D) to 152 days (subtype C). Based on the new data and revised analysis, we recommend an ODn cutoff = 1.5 to classify recent and long-term infections, corresponding to an MDRI of 130 days (118-142). Determination of revised parameters for estimation of HIV-1 incidence should facilitate application of the LAg-Avidity EIA for worldwide use.

  16. Historically aggressive types of follicular cell-derived thyroid cancer often have radioactive avid distant metastases: a study of 314 patients with distant metastases at a single institution

    Energy Technology Data Exchange (ETDEWEB)

    Tala, H.P.; Rondeau, G.; Fagin, J.A.; Tuttle, R.M. [Endocrinology Division, Department of Medicine, Nuclear Medicine Division, Memorial Sloan Kettering Cancer Center, New-York (United States); Ghossein, R.A. [Pathology Department, Nuclear Medecine Division, Memorial Sloan Kettering Cancer Center, New-York (United States); Grewal, R.K.; Larson, S.M. [Radiology Department, Nuclear Medicine Division, Memorial Sloan Kettering Cancer Center, New-York (United States)

    2012-07-01

    Radioactive iodine (RAI) remains one of the primary treatment options for metastatic, follicular cell derived thyroid cancers. The aim of this study was to determine the likelihood that metastatic lesions arising from one of the aggressive thyroid cancer histologies [tall cell variant of papillary thyroid carcinoma (TCV-PTC), poorly differentiated thyroid carcinoma (PDTC) and Hurthle cell carcinoma (HCC)] would demonstrate sufficient RAI avidity for visualization on RAI scanning and therefore could potentially benefit from RAI therapy. The study shows that in patients selected for RAI scanning or therapy at our center, RAI avid lesions can be identified in more than two thirds of the patients with distant metastases arising in the setting of C-PTC, WD-FTC, FV-PTC, TCV-PTC, or PDTC primary tumors. While RAI avidity on a post-therapy scan does not always correlate with clinically significant tumor killing activity, it is likely that some of these patients with RAI avid metastatic disease did obtain a clinical benefit

  17. Duration of (18)F-FDG avidity in lymph nodes after pandemic H1N1v and seasonal influenza vaccination

    DEFF Research Database (Denmark)

    Thomassen, Anders; Lerberg Nielsen, Anne; Gerke, Oke

    2011-01-01

    PURPOSE: The aim of our study was to investigate the occurrence of fluorodeoxyglucose (FDG) avidity in draining axillary lymph nodes after vaccination against influenza (H1N1v pandemic and seasonal) and to determine the period of increased FDG uptake. METHODS: During December 2009, patients...

  18. Usefulness of Toxoplasma gondii recombinant antigens (GRA1, GRA7 and SAG1) in an immunoglobulin G avidity test for the serodiagnosis of toxoplasmosis

    DEFF Research Database (Denmark)

    Pietkiewicz, H; Hiszczyńska-Sawicka, E; Kur, J

    2007-01-01

    The precise diagnosis of an acute and recent Toxoplasma infection in pregnant women and the newborn child is important before treatment. This study describes a new Toxoplasma gondii IgG avidity test based on a combination of recombinant GRA1, GRA7 and SAG1 antigens and shows that this test is use...

  19. Dual Testing Algorithm of BED-CEIA and AxSYM Avidity Index Assays Performs Best in Identifying Recent HIV Infection in a Sample of Rwandan Sex Workers

    NARCIS (Netherlands)

    Braunstein, Sarah L.; Nash, Denis; Kim, Andrea A.; Ford, Ken; Mwambarangwe, Lambert; Ingabire, Chantal M.; Vyankandondera, Joseph; van de Wijgert, Janneke H. H. M.

    2011-01-01

    To assess the performance of BED-CEIA (BED) and AxSYM Avidity Index (Ax-AI) assays in estimating HIV incidence among female sex workers (FSW) in Kigali, Rwanda. Eight hundred FSW of unknown HIV status were HIV tested; HIV-positive women had BED and Ax-AI testing at baseline and ≥12 months later to

  20. Antibody maturation and viral diversification in HIV-infected women.

    Directory of Open Access Journals (Sweden)

    Maria M James

    Full Text Available The Post-exposure Prophylaxis in Infants (PEPI-Malawi trial evaluated infant antiretroviral regimens for prevention of post-natal HIV transmission. A multi-assay algorithm (MAA that includes the BED capture immunoassay, an avidity assay, CD4 cell count, and viral load was used to identify women who were vs. were not recently infected at the time of enrollment (MAA recent, N = 73; MAA non-recent, N = 2,488; a subset of the women in the MAA non-recent group known to have been HIV infected for at least 2 years before enrollment (known non-recent, N = 54. Antibody maturation and viral diversification were examined in these women.Samples collected at enrollment (N = 2,561 and 12-24 months later (N = 1,306 were available for serologic analysis using the BED and avidity assays. A subset of those samples was used for analysis of viral diversity, which was performed using a high resolution melting (HRM diversity assay. Viral diversity analysis was performed using all available samples from women in the MAA recent group (61 enrollment samples, 38 follow-up samples and the known non-recent group (43 enrollment samples, 22 follow-up samples. Diversity data from PEPI-Malawi were also compared to similar data from 169 adults in the United States (US with known recent infection (N = 102 and known non-recent infection (N = 67.In PEPI-Malawi, results from the BED and avidity assays increased over time in the MAA recent group, but did not change significantly in the MAA non-recent group. At enrollment, HIV diversity was lower in the MAA recent group than in the known non-recent group. HRM diversity assay results from women in PEPI-Malawi were similar to those from adults in the US with known duration of HIV infection.Antibody maturation and HIV diversification patterns in African women provide additional support for use of the MAA to identify populations with recent HIV infection.

  1. HIV Incidence Estimates Using the Limiting Antigen Avidity EIA Assay at Testing Sites in Kiev City, Ukraine: 2013-2014

    Science.gov (United States)

    Kruglov, Yuri; Yurchenko, Alexander

    2016-01-01

    Objective To estimate HIV incidence and highlight the characteristics of persons at greatest risk of HIV in the Ukraine capital, Kiev. Method Residual samples from newly-diagnosed persons attending the Kiev City AIDS Centre were tested for evidence of recent HIV infection using an avidity assay. Questions on possible risk factors for HIV acquisition and testing history were introduced. All persons (≥16yrs) presenting for an HIV test April’13–March’14 were included. Rates per 100,000 population were calculated using region-specific denominators. Results During the study period 6370 individuals tested for HIV. Of the 467 individuals newly-diagnosed with HIV, 21 had insufficient samples for LAg testing. Of the remaining 446, 39 (8.7%) were classified as recent with an avidity index <1.5ODn, 10 were reclassified as long-standing as their viral load was <1000 copies/mL, resulting in 29 (6.5%) recent HIV infections. The only independent predictor for a recent infection was probable route of exposure, with MSM more likely to present with a recent infection compared with heterosexual contact [Odds Ratio 8.86; 95%CI 2.65–29.60]. We estimated HIV incidence at 21.5 per 100,000 population, corresponding to 466 new infections. Using population estimates for MSM and PWID, incidence was estimated to be between 2289.6 and 6868.7/100,000 MSM, and 350.4 for PWID. Conclusion A high proportion of persons newly-infected remain undiagnosed, with MSM disproportionally affected with one in four newly-HIV-diagnosed and one in three recently-HIV-infected. Our findings should be used for targeted public health interventions and health promotion. PMID:27276170

  2. HIV Incidence Estimates Using the Limiting Antigen Avidity EIA Assay at Testing Sites in Kiev City, Ukraine: 2013-2014.

    Directory of Open Access Journals (Sweden)

    Ruth Simmons

    Full Text Available To estimate HIV incidence and highlight the characteristics of persons at greatest risk of HIV in the Ukraine capital, Kiev.Residual samples from newly-diagnosed persons attending the Kiev City AIDS Centre were tested for evidence of recent HIV infection using an avidity assay. Questions on possible risk factors for HIV acquisition and testing history were introduced. All persons (≥16yrs presenting for an HIV test April'13-March'14 were included. Rates per 100,000 population were calculated using region-specific denominators.During the study period 6370 individuals tested for HIV. Of the 467 individuals newly-diagnosed with HIV, 21 had insufficient samples for LAg testing. Of the remaining 446, 39 (8.7% were classified as recent with an avidity index <1.5ODn, 10 were reclassified as long-standing as their viral load was <1000 copies/mL, resulting in 29 (6.5% recent HIV infections. The only independent predictor for a recent infection was probable route of exposure, with MSM more likely to present with a recent infection compared with heterosexual contact [Odds Ratio 8.86; 95%CI 2.65-29.60]. We estimated HIV incidence at 21.5 per 100,000 population, corresponding to 466 new infections. Using population estimates for MSM and PWID, incidence was estimated to be between 2289.6 and 6868.7/100,000 MSM, and 350.4 for PWID.A high proportion of persons newly-infected remain undiagnosed, with MSM disproportionally affected with one in four newly-HIV-diagnosed and one in three recently-HIV-infected. Our findings should be used for targeted public health interventions and health promotion.

  3. HIV Incidence Estimates Using the Limiting Antigen Avidity EIA Assay at Testing Sites in Kiev City, Ukraine: 2013-2014.

    Science.gov (United States)

    Simmons, Ruth; Malyuta, Ruslan; Chentsova, Nelli; Karnets, Iryna; Murphy, Gary; Medoeva, Antonia; Kruglov, Yuri; Yurchenko, Alexander; Copas, Andrew; Porter, Kholoud

    2016-01-01

    To estimate HIV incidence and highlight the characteristics of persons at greatest risk of HIV in the Ukraine capital, Kiev. Residual samples from newly-diagnosed persons attending the Kiev City AIDS Centre were tested for evidence of recent HIV infection using an avidity assay. Questions on possible risk factors for HIV acquisition and testing history were introduced. All persons (≥16yrs) presenting for an HIV test April'13-March'14 were included. Rates per 100,000 population were calculated using region-specific denominators. During the study period 6370 individuals tested for HIV. Of the 467 individuals newly-diagnosed with HIV, 21 had insufficient samples for LAg testing. Of the remaining 446, 39 (8.7%) were classified as recent with an avidity index <1.5ODn, 10 were reclassified as long-standing as their viral load was <1000 copies/mL, resulting in 29 (6.5%) recent HIV infections. The only independent predictor for a recent infection was probable route of exposure, with MSM more likely to present with a recent infection compared with heterosexual contact [Odds Ratio 8.86; 95%CI 2.65-29.60]. We estimated HIV incidence at 21.5 per 100,000 population, corresponding to 466 new infections. Using population estimates for MSM and PWID, incidence was estimated to be between 2289.6 and 6868.7/100,000 MSM, and 350.4 for PWID. A high proportion of persons newly-infected remain undiagnosed, with MSM disproportionally affected with one in four newly-HIV-diagnosed and one in three recently-HIV-infected. Our findings should be used for targeted public health interventions and health promotion.

  4. Chimeric PD-1:28 Receptor Upgrades Low-Avidity T cells and Restores Effector Function of Tumor-Infiltrating Lymphocytes for Adoptive Cell Therapy.

    Science.gov (United States)

    Schlenker, Ramona; Olguín-Contreras, Luis Felipe; Leisegang, Matthias; Schnappinger, Julia; Disovic, Anja; Rühland, Svenja; Nelson, Peter J; Leonhardt, Heinrich; Harz, Hartmann; Wilde, Susanne; Schendel, Dolores J; Uckert, Wolfgang; Willimsky, Gerald; Noessner, Elfriede

    2017-07-01

    Inherent intermediate- to low-affinity T-cell receptors (TCR) that develop during the natural course of immune responses may not allow sufficient activation for tumor elimination, making the majority of T cells suboptimal for adoptive T-cell therapy (ATT). TCR affinity enhancement has been implemented to provide stronger T-cell activity but carries the risk of creating undesired cross-reactivity leading to potential serious adverse effects in clinical application. We demonstrate here that engineering of low-avidity T cells recognizing a naturally processed and presented tumor-associated antigen with a chimeric PD-1:28 receptor increases effector function to levels seen with high-avidity T cells of identical specificity. Upgrading the function of low-avidity T cells without changing the TCR affinity will allow a large arsenal of low-avidity T cells previously thought to be therapeutically inefficient to be considered for ATT. PD-1:28 engineering reinstated Th1 function in tumor-infiltrating lymphocytes that had been functionally disabled in the human renal cell carcinoma environment without unleashing undesired Th2 cytokines or IL10. Involved mechanisms may be correlated to restoration of ERK and AKT signaling pathways. In mouse tumor models of ATT, PD-1:28 engineering enabled low-avidity T cells to proliferate stronger and prevented PD-L1 upregulation and Th2 polarization in the tumor milieu. Engineered T cells combined with checkpoint blockade secreted significantly more IFNγ compared with T cells without PD-1:28, suggesting a beneficial combination with checkpoint blockade therapy or other therapeutic strategies. Altogether, the supportive effects of PD-1:28 engineering on T-cell function make it an attractive tool for ATT. Cancer Res; 77(13); 3577-90. ©2017 AACR . ©2017 American Association for Cancer Research.

  5. Fusion proteins of HIV-1 envelope glycoprotein gp120 with CD4-induced antibodies showed enhanced binding to CD4 and CD4 binding site antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Weizao, E-mail: chenw3@mail.nih.gov [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Feng, Yang [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Wang, Yanping [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); The Basic Research Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Zhu, Zhongyu; Dimitrov, Dimiter S. [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer Some recombinant HIV-1 gp120s do not preserve their conformations on gp140s. Black-Right-Pointing-Pointer We hypothesize that CD4i antibodies could induce conformational changes in gp120. Black-Right-Pointing-Pointer CD4i antibodies enhance binding of CD4 and CD4bs antibodies to gp120. Black-Right-Pointing-Pointer CD4i antibody-gp120 fusion proteins could have potential as vaccine immunogens. -- Abstract: Development of successful AIDS vaccine immunogens continues to be a major challenge. One of the mechanisms by which HIV-1 evades antibody-mediated neutralizing responses is the remarkable conformational flexibility of its envelope glycoprotein (Env) gp120. Some recombinant gp120s do not preserve their conformations on gp140s and functional viral spikes, and exhibit decreased recognition by CD4 and neutralizing antibodies. CD4 binding induces conformational changes in gp120 leading to exposure of the coreceptor-binding site (CoRbs). In this study, we test our hypothesis that CD4-induced (CD4i) antibodies, which target the CoRbs, could also induce conformational changes in gp120 leading to better exposed conserved neutralizing antibody epitopes including the CD4-binding site (CD4bs). We found that a mixture of CD4i antibodies with gp120 only weakly enhanced CD4 binding. However, such interactions in single-chain fusion proteins resulted in gp120 conformations which bound to CD4 and CD4bs antibodies better than the original or mutagenically stabilized gp120s. Moreover, the two molecules in the fusion proteins synergized with each other in neutralizing HIV-1. Therefore, fusion proteins of gp120 with CD4i antibodies could have potential as components of HIV-1 vaccines and inhibitors of HIV-1 entry, and could be used as reagents to explore the conformational flexibility of gp120 and mechanisms of entry and immune evasion.

  6. The West Nile virus assembly process evades the conserved antiviral mechanism of the interferon-induced MxA protein

    Energy Technology Data Exchange (ETDEWEB)

    Hoenen, Antje [School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane (Australia); Gillespie, Leah [Department of Microbiology, La Trobe University, Melbourne (Australia); Department of Microbiology and Immunology, University of Melbourne, Melbourne (Australia); Morgan, Garry; Heide, Peter van der [Institute for Molecular Bioscience, University of Queensland, Brisbane (Australia); Khromykh, Alexander [School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane (Australia); Australian Infectious Diseases Research Centre, University of Queensland, Brisbane (Australia); Mackenzie, Jason, E-mail: jason.mackenzie@unimelb.edu.au [Department of Microbiology, La Trobe University, Melbourne (Australia); Department of Microbiology and Immunology, University of Melbourne, Melbourne (Australia)

    2014-01-05

    Flaviviruses have evolved means to evade host innate immune responses. Recent evidence suggests this is due to prevention of interferon production and signaling in flavivirus-infected cells. Here we show that the interferon-induced MxA protein can sequester the West Nile virus strain Kunjin virus (WNV{sub KUN}) capsid protein in cytoplasmic tubular structures in an expression-replication system. This sequestering resulted in reduced titers of secreted WNV{sub KUN} particles. We show by electron microscopy, tomography and 3D modeling that these cytoplasmic tubular structures form organized bundles. Additionally we show that recombinant ER-targeted MxA can restrict production of infectious WNV{sub KUN} under conditions of virus infection. Our results indicate a co-ordinated and compartmentalized WNV{sub KUN} assembly process may prevent recognition of viral components by MxA, particularly the capsid protein. This recognition can be exploited if MxA is targeted to intracellular sites of WNV{sub KUN} assembly. This results in further understanding of the mechanisms of flavivirus evasion from the immune system. - Highlights: • We show that the ISG MxA can recognize the West Nile virus capsid protein. • Interaction between WNV C protein and MxA induces cytoplasmic fibrils. • MxA can be retargeted to the ER to restrict WNV particle release. • WNV assembly process is a strategy to avoid MxA recognition.

  7. Cooperative option of pursuit game with two pursuers and one evader. A strong stability of division variety

    Directory of Open Access Journals (Sweden)

    Viktor D. Shiryayev

    2017-06-01

    Full Text Available Introduction: The article deals with a simple differential game on the plane of pursuit with two consistently active players and one evader E; the game is considered in the form of the characteristic function. Materials and Methods: The geometric constructions and methods are used for solving the problem. The security zone of the escapee is bounded by the Apollonius circle, the pursuit team uses a strategy of parallel approach. Results: A method of finding the optimal players strategies and the optimal players’ trajectory is proposed. The way of forming the characteristic function is provided. All the variety of division is considered as a solution. However, the use of the results of cooperative theory of differential games is impossible without solving the problems associated with the specifics of differential equations of motion. Foremost, it is the problem of dynamic stability of optimality principles. The article introduces an auxiliary function of making the redistribution of winnings in time, keeping his total winnings throughout the game. The dynamic stability of the cooperative solution is determined with the help of this function. Strong dynamic stability of the entire set of solutions is shown. Discussion and Conclusions: The obtained results are consistent with similar research of other authors. Further research in this field can be used in the development of methods for “regularization” of optimality principles, for which the condition of dynamic stability is always fulfilled.

  8. Pasteurella pneumotropica evades the human complement system by acquisition of the complement regulators factor H and C4BP.

    Directory of Open Access Journals (Sweden)

    Alfredo Sahagún-Ruiz

    Full Text Available Pasteurella pneumotropica is an opportunist Gram negative bacterium responsible for rodent pasteurellosis that affects upper respiratory, reproductive and digestive tracts of mammals. In animal care facilities the presence of P. pneumotropica causes severe to lethal infection in immunodeficient mice, being also a potential source for human contamination. Indeed, occupational exposure is one of the main causes of human infection by P. pneumotropica. The clinical presentation of the disease includes subcutaneous abscesses, respiratory tract colonization and systemic infections. Given the ability of P. pneumotropica to fully disseminate in the organism, it is quite relevant to study the role of the complement system to control the infection as well as the possible evasion mechanisms involved in bacterial survival. Here, we show for the first time that P. pneumotropica is able to survive the bactericidal activity of the human complement system. We observed that host regulatory complement C4BP and Factor H bind to the surface of P. pneumotropica, controlling the activation pathways regulating the formation and maintenance of C3-convertases. These results show that P. pneumotropica has evolved mechanisms to evade the human complement system that may increase the efficiency by which this pathogen is able to gain access to and colonize inner tissues where it may cause severe infections.

  9. Escape and evade control policies for ensuring the physical security of nonholonomic, ground-based, unattended mobile sensor nodes

    Science.gov (United States)

    Mascarenas, David; Stull, Christopher; Farrar, Charles

    2011-06-01

    In order to realize the wide-scale deployment of high-endurance, unattended mobile sensing technologies, it is vital to ensure the self-preservation of the sensing assets. Deployed mobile sensor nodes face a variety of physical security threats including theft, vandalism and physical damage. Unattended mobile sensor nodes must be able to respond to these threats with control policies that facilitate escape and evasion to a low-risk state. In this work the Precision Immobilization Technique (PIT) problem has been considered. The PIT maneuver is a technique that a pursuing, car-like vehicle can use to force a fleeing vehicle to abruptly turn ninety degrees to the direction of travel. The abrupt change in direction generally causes the fleeing driver to lose control and stop. The PIT maneuver was originally developed by law enforcement to end vehicular pursuits in a manner that minimizes damage to the persons and property involved. It is easy to imagine that unattended autonomous convoys could be targets of this type of action by adversarial agents. This effort focused on developing control policies unattended mobile sensor nodes could employ to escape, evade and recover from PIT-maneuver-like attacks. The development of these control policies involved both simulation as well as small-scale experimental testing. The goal of this work is to be a step toward ensuring the physical security of unattended sensor node assets.

  10. The p75 neurotrophin receptor evades the endolysosomal route in neuronal cells, favouring multivesicular bodies specialised for exosomal release

    Science.gov (United States)

    Escudero, Claudia A.; Lazo, Oscal M.; Galleguillos, Carolina; Parraguez, Jose I.; Lopez-Verrilli, Maria A.; Cabeza, Carolina; Leon, Luisa; Saeed, Uzma; Retamal, Claudio; Gonzalez, Alfonso; Marzolo, Maria-Paz; Carter, Bruce D.; Court, Felipe A.; Bronfman, Francisca C.

    2014-01-01

    ABSTRACT The p75 neurotrophin receptor (p75, also known as NGFR) is a multifaceted signalling receptor that regulates neuronal physiology, including neurite outgrowth, and survival and death decisions. A key cellular aspect regulating neurotrophin signalling is the intracellular trafficking of their receptors; however, the post-endocytic trafficking of p75 is poorly defined. We used sympathetic neurons and rat PC12 cells to study the mechanism of internalisation and post-endocytic trafficking of p75. We found that p75 internalisation depended on the clathrin adaptor protein AP2 and on dynamin. More surprisingly, p75 evaded the lysosomal route at the level of the early endosome, instead accumulating in two different types of endosomes, Rab11-positive endosomes and multivesicular bodies (MVBs) positive for CD63, a marker of the exosomal pathway. Consistently, depolarisation by KCl induced the liberation of previously endocytosed full-length p75 into the extracellular medium in exosomes. Thus, p75 defines a subpopulation of MVBs that does not mature to lysosomes and is available for exosomal release by neuronal cells. PMID:24569882

  11. Phage Fab Display Selection In Vitro and In Vivo: Novel Means to Identify New Breast Cancer Avid Compounds

    National Research Council Canada - National Science Library

    Meighan, Mark

    2001-01-01

    .... In this annual report we present preliminary results on the isolation of antibody fragments (Fabs), isolated from phage display libraries, when affinity selected against breast cancer cell lines...

  12. Antibodies and Selection of Monoclonal Antibodies.

    Science.gov (United States)

    Hanack, Katja; Messerschmidt, Katrin; Listek, Martin

    Monoclonal antibodies are universal binding molecules with a high specificity for their target and are indispensable tools in research, diagnostics and therapy. The biotechnological generation of monoclonal antibodies was enabled by the hybridoma technology published in 1975 by Köhler and Milstein. Today monoclonal antibodies are used in a variety of applications as flow cytometry, magnetic cell sorting, immunoassays or therapeutic approaches. First step of the generation process is the immunization of the organism with appropriate antigen. After a positive immune response the spleen cells are isolated and fused with myeloma cells in order to generate stable, long-living antibody-producing cell lines - hybridoma cells. In the subsequent identification step the culture supernatants of all hybridoma cells are screened weekly for the production of the antibody of interest. Hybridoma cells producing the antibody of interest are cloned by limited dilution till a monoclonal hybridoma is found. This is a very time-consuming and laborious process and therefore different selection strategies were developed since 1975 in order to facilitate the generation of monoclonal antibodies. Apart from common automation of pipetting processes and ELISA testing there are some promising approaches to select the right monoclonal antibody very early in the process to reduce time and effort of the generation. In this chapter different selection strategies for antibody-producing hybridoma cells are presented and analysed regarding to their benefits compared to conventional limited dilution technology.

  13. Anti-dog IgG secondary antibody successfully detects IgG in a variety of aquatic mammals

    Science.gov (United States)

    Roehl, Katherine; Jankowski, Mark D.; Hofmeister, Erik K.

    2016-01-01

    Serological tests play an important role in the detection of wildlife diseases. However, while there are many commercial assays and reagents available for domestic species, there is a need to develop efficient serological assays for wildlife. In recent years, marine mammals have represented a wildlife group with emerging infectious diseases, such as influenza, brucellosis, and leptospirosis. However, with the exception of disease-agent-specific assays or functional assays, few reports describe the use of antibody detection assays in marine mammals. In an indirect enzyme-linked immunoassay (EIA) or an immunofluorescence assay, antibody is detected using an antitarget species secondary conjugated antibody. The sensitivity of the assay depends on the avidity of the binding reaction between the bound antibody and the detection antibody. A commercial polyclonal antidog IgG conjugated antibody was tested in an EIA for its ability to sensitively detect the IgG of seven marine mammals including sea otter (Enhydra lutris), polar bear (Ursus maritimus), grey seal (Halichoerus grypus), harbor seal (Phoca vitulina), northern elephant seal (Mirounga angustirostris), California sea lion (Zalophus californianus), Pacific walrus (Odobenus rosmarus) and one freshwater mammal: Asian small-clawed otter (Aonyx cinerea). With the exception of Asian small-clawed sea otters, the detection of IgG in these marine mammals either exceeded or was nearly equal to detection of dog IgG. The use of the tested commercial antidog IgG antibody may be a valid approach to the detection of antibody response to disease in sea mammals.

  14. Uudised : Üheteistkümnendad trompetipäevad. Eesti Muusikanõukogus. Tüüri "Motus I" Londonis / Kadri Ruudi

    Index Scriptorium Estoniae

    Ruudi, Kadri

    2000-01-01

    4.-15. apr. toimuvad EMA XI trompetipäevad. 14.-19. märtsil viibis Eestis IMC asepresident F. Müller-Heuser, 22. märtsil toimus EMN juhatuse koosolek. 19. märtsil andis Londoni South Bank Centre'is kontserdi P. Carneiro, kes tõi Inglismaal esiettekandele ka E.-S. Tüüri teose "Motus I"

  15. EST: Evading Scientific Text.

    Science.gov (United States)

    Ward, Jeremy

    2001-01-01

    Examines chemical engineering students' attitudes to text and other parts of English language textbooks. A questionnaire was administered to a group of undergraduates. Results reveal one way students get around the problem of textbook reading. (Author/VWL)

  16. Evading the Boomerang Effect

    DEFF Research Database (Denmark)

    Laursen, Keld; Moreira, Solon; Reichstein, Toke

    2017-01-01

    Technology licensing agreements potentially can create future appropriability problems. Drawing on the appropriability literature, we argue that the inclusion of a grant-back clause in technology licensing agreements is an attempt to balance the gains from and protection of the focal firms’ techn...

  17. Evading the CKM Hierarchy

    International Nuclear Information System (INIS)

    Brodsky, Stanley J.

    2001-01-01

    We show that the presence of intrinsic charm in the hadrons' light-cone wave functions, even at a few percent level, provides new, competitive decay mechanisms for B decays which are nominally CKM-suppressed. For example, the weak decays of the B-meson to two-body exclusive states consisting of strange plus light hadrons, such as B → π K, are expected to be dominated by penguin contributions since the tree-level b → s u bar u decay is CKM suppressed However, higher Fock states in the B wave function containing charm quark pairs can mediate the decay via a CKM-favored b → s cbar c tree-level transition. Such intrinsic charm contributions can be phenomenologically significant. Since they mimic the amplitude structure of ''charming'' penguin contributions, charming penguins need not be penguins at all

  18. Lyme disease antibody

    Science.gov (United States)

    ... JavaScript. The Lyme disease blood test looks for antibodies in the blood to the bacteria that causes ... needed. A laboratory specialist looks for Lyme disease antibodies in the blood sample using the ELISA test . ...

  19. Antinuclear antibody panel

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003535.htm Antinuclear antibody panel To use the sharing features on this page, please enable JavaScript. The antinuclear antibody panel is a blood test that looks at ...

  20. Acetylcholine receptor antibody

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003576.htm Acetylcholine receptor antibody To use the sharing features on this page, please enable JavaScript. Acetylcholine receptor antibody is a protein found in the blood of ...

  1. Nuclear medicine: Monoclonal antibodies

    International Nuclear Information System (INIS)

    Endo, K.; Sakahara, H.; Koizumi, M.; Kawamura, Y.; Torizuka, K.; Yokoyama, A.

    1986-01-01

    Antitumor monoclonal antibody was successfully labeled with Tc-99m by using dithiosemicarbazone (DTS) as a bifunctional chelating agent. In the first step, DTS was coupled to antibody without loss of immunoreactivity; the compound then efficiently formed a neutral 1:1 chelate with pentavalent or tetravalent Tc-99m. Imaging with Tc-99m-labeled monoclonal antibody to human osteosarcoma (OST-7) clearly displayed a small tumor in nude mice at 6 and 24 hours after intravenous administration. The tumor-to-blood ratio of the Tc-99m-labeled monoclonal antibody was higher than that of a radioiodinated antibody and similar to that of an In-111-labeled antibody. Thus, conjugation of DTS to monoclonal antibody followed by radiometalation is a simple and efficient method of preparing Tc-99m-labeled monoclonal antibody

  2. Platelet antibodies blood test

    Science.gov (United States)

    This blood test shows if you have antibodies against platelets in your blood. Platelets are a part of the blood ... Chernecky CC, Berger BJ. Platelet antibody - blood. In: Chernecky ... caused by platelet destruction, hypersplenism, or hemodilution. ...

  3. Primary Nocardia Infection Causing a Fluorodeoxyglucose-Avid Right Renal Mass in a Redo Lung Transplant Recipient

    Directory of Open Access Journals (Sweden)

    Sreeja Biswas Roy

    2018-01-01

    Full Text Available Immunosuppression after lung transplantation may increase susceptibility to opportunistic infection and is associated with early and delayed deaths in lung transplant recipients. Factors that may predispose lung transplant recipients to opportunistic bacterial and fungal infections include prolonged corticosteroid use, renal impairment, treatment of acute rejection, and post-transplant diabetes mellitus. We present a unique case of a 63-year-old woman with diabetes mellitus who underwent redo lung transplantation. Three years after her right-sided single redo lung transplant, she presented with right-sided abdominal pain, nausea, and vomiting. Upon examination, computed tomography showed a 4.5 × 3.3 cm heterogeneous, enhancing right renal mass with a patent renal vein. Magnetic resonance imaging confirmed a T1/T2 hypointense, diffusion-restricting, right mid-renal mass that was fluorodeoxyglucose-avid on positron emission tomography. We initially suspected primary renal cell carcinoma. However, after a right nephrectomy, no evidence of neoplasia was observed; instead, a renal abscess containing filamentous bacteria was noted, raising suspicion for infection of the Nocardia species. Special stains confirmed a diagnosis of Nocardia renal abscess. Computed tomography of the chest and brain revealed no lesions consistent with infection. We initiated a long-term therapeutic regimen of anti-Nocardia therapy with imipenem and trimethoprim-sulfamethoxazole.

  4. Metastatic Follicular Thyroid Carcinoma Secreting Thyroid Hormone and Radioiodine Avid without Stimulation: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Syed A. Abid

    2014-01-01

    Full Text Available Introduction. This is an extremely rare case of a patient with metastatic follicular thyroid cancer who continued to produce thyroid hormone and was iodine scan positive without stimulation after thyroidectomy and radioiodine (I-131 therapy. Patient Findings. A 76-year-old Caucasian male was diagnosed with metastatic follicular thyroid carcinoma on lung nodule biopsy. Total thyroidectomy was performed and he was ablated with 160 mCi of I-131 after recombinant human thyrotropin (rhTSH stimulation. Whole body scan (WBS after treatment showed uptake in bilateral lungs, right sacrum, and pelvis. The thyroglobulin decreased from 2,063 to 965 four months after treatment but rapidly increased to 2,506 eleven months after I-131. Thyroid stimulating hormone (TSH remained suppressed and free T4 remained elevated after I-131 therapy without thyroid hormone supplementation. He was treated with an additional 209 mCi with WBS findings positive in lung and pelvis. Despite I-131, new metastatic lesions were noted in the left thyroid bed and large destructive lesion to the first cervical vertebrae four months after the second I-131 dose. Conclusions. This case is exceptional because of its rarity and also due to the dissociation between tumor differentiation and aggressiveness. The metastatic lesions continued to secrete thyroid hormone and remained radioiodine avid with rapid progression after I-131 therapy.

  5. Discovery of Radioiodinated Monomeric Anthraquinones as a Novel Class of Necrosis Avid Agents for Early Imaging of Necrotic Myocardium.

    Science.gov (United States)

    Wang, Qin; Yang, Shengwei; Jiang, Cuihua; Li, Jindian; Wang, Cong; Chen, Linwei; Jin, Qiaomei; Song, Shaoli; Feng, Yuanbo; Ni, Yicheng; Zhang, Jian; Yin, Zhiqi

    2016-02-16

    Assessment of myocardial viability is deemed necessary to aid in clinical decision making whether to recommend revascularization therapy for patients with myocardial infarction (MI). Dianthraquinones such as hypericin (Hyp) selectively accumulate in necrotic myocardium, but were unsuitable for early imaging after administration to assess myocardial viability. Since dianthraquinones can be composed by coupling two molecules of monomeric anthraquinone and the active center can be found by splitting chemical structure, we propose that monomeric anthraquinones may be effective functional groups for necrosis targetability. In this study, eight radioiodinated monomeric anthraquinones were evaluated as novel necrosis avid agents (NAAs) for imaging of necrotic myocardium. All (131)I-anthraquinones showed high affinity to necrotic tissues and (131)I-rhein emerged as the most promising compound. Infarcts were visualized on SPECT/CT images at 6 h after injection of (131)I-rhein, which was earlier than that with (131)I-Hyp. Moreover, (131)I-rhein showed satisfactory heart-to-blood, heart-to-liver and heart-to-lung ratios for obtaining images of good diagnostic quality. (131)I-rhein was a more promising "hot spot imaging" tracer for earlier visualization of necrotic myocardium than (131)I-Hyp, which supported further development of radiopharmaceuticals based on rhein for SPECT/CT ((123)I and (99m)Tc) or PET/CT imaging ((18)F and (124)I) of myocardial necrosis.

  6. Heavy chain only antibodies

    DEFF Research Database (Denmark)

    Moghimi, Seyed Moein; Rahbarizadeh, Fatemeh; Ahmadvand, Davoud

    2013-01-01

    Unlike conventional antibodies, heavy chain only antibodies derived from camel contain a single variable domain (VHH) and two constant domains (CH2 and CH3). Cloned and isolated VHHs possess unique properties that enable them to excel conventional therapeutic antibodies and their smaller antigen...

  7. Hepatitis A virus antibody

    International Nuclear Information System (INIS)

    Novak, J.; Kselikova, M.; Urbankova, J.

    1980-01-01

    A description is presented of a radioimmunoassay designed to prove the presence of the antibody against the hepatitis A virus (HA Ab, anti-Ha) using an Abbott HAVAB set. This proof as well as the proof of the antibody against the nucleus of the hepatitis B virus is based on competition between a normal antibody against hepatitis A virus and a 125 I-labelled antibody for the binding sites of a specific antigen spread all over the surface of a tiny ball; this is then indirect proof of the antibody under investigation. The method is described of reading the results from the number of impulses per 60 seconds: the higher the titre of the antibody against the hepatitis A virus in the serum examined, the lower the activity of the specimen concerned. The rate is reported of incidence of the antibody against the hepatitis A virus in a total of 68 convalescents after hepatitis A; the antibody was found in 94.1%. The immunoglobulin made from the convalescents' plasma showed the presence of antibodies in dilutions as high as 1:250 000 while the comparable ratio for normal immunoglobulin Norga was only 1:2500. Differences are discussed in the time incidence of the antibodies against the hepatitis A virus, the antibodies against the surface antigen of hepatitis B, and the antibody against the nucleus of the hepatitis V virus. (author)

  8. Anti-insulin antibody test

    Science.gov (United States)

    Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... Normally, there are no antibodies against insulin in your blood. ... different laboratories. Some labs use different measurements or ...

  9. Monoclonal antibodies and cancer

    International Nuclear Information System (INIS)

    Haisma, H.J.

    1987-01-01

    The usefulness of radiolabeled monoclonal antibodies for imaging and treatment of human (ovarian) cancer was investigated. A review of tumor imaging with monoclonal antibodies is presented. Special attention is given to factors that influence the localization of the antibodies in tumors, isotope choice and methods of radiolabeling of the monoclonal antibodies. Two monoclonal antibodies, OC125 and OV-TL3, with high specificity for human epithelial ovarian cancer are characterized. A simple radio-iodination technique was developed for clinical application of the monoclonal antibodies. The behavior of monoclonal antibodies in human tumor xenograft systems and in man are described. Imaging of tumors is complicated because of high background levels of radioactivity in other sites than the tumor, especially in the bloodpool. A technique was developed to improve imaging of human tumor xenographs in nude mice, using subtraction of a specific and a non-specific antibody, radiolabeled with 111 In, 67 Ga and 131 I. To investigate the capability of the two monoclonal antibodies, to specifically localize in human ovarian carcinomas, distribution studies in mice bearing human ovarian carcinoma xenografts were performed. One of the antibodies, OC125, was used for distribution studies in ovarian cancer patients. OC125 was used because of availability and approval to use this antibody in patients. The same antibody was used to investigate the usefulness of radioimmunoimaging in ovarian cancer patients. The interaction of injected radiolabeled antibody OC125 with circulating antigen and an assay to measure the antibody response in ovarian cancer patients after injection of the antibody is described. 265 refs.; 30 figs.; 19 tabs

  10. Antiparasitic effects induced by polyclonal IgY antibodies anti-phospholipase A2 from Bothrops pauloensis venom.

    Science.gov (United States)

    Borges, Isabela Pacheco; Silva, Mariana Ferreira; Santiago, Fernanda Maria; de Faria, Lucas Silva; Júnior, Álvaro Ferreira; da Silva, Rafaela José; Costa, Mônica Soares; de Freitas, Vitor; Yoneyama, Kelly Aparecida Geraldo; Ferro, Eloísa Amália Vieira; Lopes, Daiana Silva; Rodrigues, Renata Santos; de Melo Rodrigues, Veridiana

    2018-06-01

    Activities of phospholipases (PLAs) have been linked to pathogenesis in various microorganisms, and implicated in cell invasion and so the interest in these enzymes as potential targets that could contribute to the control of parasite survival and proliferation. Chicken eggs immunized with BnSP-7, a Lys49 phospholipase A 2 (PLA 2 ) homologue from Bothrops pauloensis snake venom, represent an excellent source of polyclonal antibodies with potential inhibitory activity on parasite PLA s. Herein, we report the production, characterization and anti-parasitic effect of IgY antibodies from egg yolks of hens immunized with BnSP-7. Produced antibodies presented increasing avidity and affinity for antigenic toxin epitopes throughout immunization, attaining a plateau after 4weeks. Pooled egg yolks-purified anti-BnSP-7 IgY antibodies were able to specifically recognize different PLA 2 s from Bothrops pauloensis and Bothrops jararacussu venom. Antibodies also neutralized BnSP-7 cytotoxic activity in C2C12 cells. Also, the antibodies recognized targets in Leishmania (Leishmania) amazonensis and Toxoplasma gondii extracts by ELISA and immunofluorescence assays. Anti-BnSP-7 IgY antibodies were cytotoxic to T. gondii tachyzoite and L. (L.) amazonensis promastigotes, and were able to decrease proliferation of both parasites treated before infection. These data suggest that the anti-BnSP-7 IgY is an important tool for discovering new parasite targets and blocking parasitic effects. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. General approach to standardization of the solid-phase radioimmunoassay for quantitation of class-specific antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Zollinger, W D; Boslego, J W [Walter Reed Army Inst. of Research, Washington, DC (USA)

    1981-10-30

    The feasibility of using an anti-human immunoglobulin/human immunoglobulin/(/sup 125/I)anti-human immunoglobulin 'sandwich' in a solid-phase radioimmunoassay to produce a standard curve which could be used to quantitate antigen-specific antibody of a particular immunoglobulin class was investigated. The amount of secondary antibody (SAb) bound was determined as a function of whether the primary antibody (PAb) was bound to its specific solid-phase antigen or by a solid-phase anti-human immunoglobulin. No significant difference between the two values was observed. Quantitation of anti-tetanus toxoid antibody by this method was in a good agreement with quantitative precipitin tests. Comparison of SAb binding as a function of the way the PAb is bound was extended to class-specific PAb by use of murine monoclonal antibodies to meningococcal antigens. In most cases somewhat greater binding of SAb occurred when PAb was bound to antigen, but in several cases where low avidity antibody and/or poor quality antigens were used, greater SAb binding occurred when PAb was bound by anti-mouse immunoglobulin. The results indicate that this approach may be useful as a general method for standardizing the SPRIA and other solid-phase immunoassays such as the ELISA to measure class-specific antibody.

  12. Pentavalent single-domain antibodies reduce Campylobacter jejuni motility and colonization in chickens.

    Directory of Open Access Journals (Sweden)

    Ali Riazi

    Full Text Available Campylobacter jejuni is the leading cause of bacterial foodborne illness in the world, with symptoms ranging from acute diarrhea to severe neurological disorders. Contaminated poultry meat is a major source of C. jejuni infection, and therefore, strategies to reduce this organism in poultry, are expected to reduce the incidence of Campylobacter-associated diseases. We have investigated whether oral administration of C. jejuni-specific single-domain antibodies would reduce bacterial colonization levels in chickens. Llama single-domain antibodies specific for C. jejuni were isolated from a phage display library generated from the heavy chain IgG variable domain repertoire of a llama immunized with C. jejuni flagella. Two flagella-specific single-domain antibodies were pentamerized to yield high avidity antibodies capable of multivalent binding to the target antigen. When administered orally to C. jejuni-infected two-day old chicks, the pentabodies significantly reduced C. jejuni colonization in the ceca. In vitro, the motility of the bacteria was also reduced in the presence of the flagella-specific pentabodies, suggesting the mechanism of action is through either direct interference with flagellar motility or antibody-mediated aggregation. Fluorescent microscopy and Western blot analyses revealed specific binding of the anti-flagella pentabodies to the C. jejuni flagellin.

  13. [VGKC-complex antibodies].

    Science.gov (United States)

    Watanabe, Osamu

    2013-04-01

    Various antibodies are associated with voltage-gated potassium channels (VGKCs). Representative antibodies to VGKCs were first identified by radioimmunoassays using radioisotope-labeled alpha-dendrotoxin-VGKCs solubilized from rabbit brain. These antibodies were detected only in a proportion of patients with acquired neuromyotonia (Isaacs' syndrome). VGKC antibodies were also detected in patients with Morvan's syndrome and in those with a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC" antibodies are mainly directed toward associated proteins (for example LGI-1 and CASPR-2) that complex with the VGKCs themselves. The "VGKC" antibodies are now commonly known as VGKC-complex antibodies. In general, LGI-1 antibodies are most commonly detected in patients with limbic encephalitis with syndrome of inappropriate secretion of antidiuretic hormone. CASPR-2 antibodies are present in the majority of patients with Morvan's syndrome. These patients develop combinations of CNS symptoms, autonomic dysfunction, and peripheral nerve hyperexcitability. Furthermore, VGKC-complex antibodies are tightly associated with chronic idiopathic pain. Hyperexcitability of nociceptive pathways has also been implicated. These antibodies may be detected in sera of some patients with neurodegenerative diseases (for example, amyotrophic lateral sclerosis and Creutzfeldt-Jakob disease).

  14. Thermodynamic Mechanism for the Evasion of Antibody Neutralization in Flaviviruses

    Science.gov (United States)

    2015-01-01

    Mutations in the epitopes of antigenic proteins can confer viral resistance to antibody-mediated neutralization. However, the fundamental properties that characterize epitope residues and how mutations affect antibody binding to alter virus susceptibility to neutralization remain largely unknown. To address these questions, we used an ensemble-based algorithm to characterize the effects of mutations on the thermodynamics of protein conformational fluctuations. We applied this method to the envelope protein domain III (ED3) of two medically important flaviviruses: West Nile and dengue 2. We determined an intimate relationship between the susceptibility of a residue to thermodynamic perturbations and epitope location. This relationship allows the successful identification of the primary epitopes in each ED3, despite their high sequence and structural similarity. Mutations that allow the ED3 to evade detection by the antibody either increase or decrease conformational fluctuations of the epitopes through local effects or long-range interactions. Spatially distant interactions originate in the redistribution of conformations of the ED3 ensembles, not through a mechanically connected array of contiguous amino acids. These results reconcile previous observations of evasion of neutralization by mutations at a distance from the epitopes. Finally, we established a quantitative correlation between subtle changes in the conformational fluctuations of the epitope and large defects in antibody binding affinity. This correlation suggests that mutations that allow viral growth, while reducing neutralization, do not generate significant structural changes and underscores the importance of protein fluctuations and long-range interactions in the mechanism of antibody-mediated neutralization resistance. PMID:24950171

  15. Radiolabeled antibody imaging

    International Nuclear Information System (INIS)

    Wahl, R.L.

    1987-01-01

    Radiolabeled antibodies, in particular monoclonal antibodies, offer the potential for the specific nuclear imaging of malignant and benign diseases in man. If this imaging potential is realized, they may also have a large role in cancer treatment. This paper reviews: (1) what monoclonal antibodies are and how they differ from polyclonal antibodies, (2) how they are produced and radiolabeled, (3) the results of preclinical and clinical trials in cancer imaging, including the utility of SPECT and antibody fragments, (4) the role of antibodies in the diagnosis of benign diseases, (5) alternate routes of antibody delivery, (6) the role of these agents in therapy, and (7) whether this technology ''revolutionizes'' the practice of nuclear radiology, or has a more limited complementary role in the imaging department

  16. Normal physiologic and Benign foci with F-18 FDG avidity on PET/CT in patients with breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Park, Soon Ah; Lee, Kwang Man; Choi, Un Jong; Kim, Hun Soo; Kim, Hye Won; Song, Jeong Hoon [College of Medicine, Wonkwnag University, Iksan (Korea, Republic of)

    2010-12-15

    The aim of this study was to evaluate the physiologic and benign F-18 fluorodeoxyglucose (FDG) avid foci in patients with breast cancer. On 309 F-18 FDG PET/CT scans of 241 women with breast cancer, the hypermetabolic lesions compared with the surrounding normal region were evaluated retrospectively. Available reports of other relevant radiological imaging medical records, and follow-up PET/CT were reviewed for explanations of the abnormal uptake. Among the 70 physiologic foci, muscular uptake of the lower neck following the surgical and/or radiation therapy of ipsilateral breast (29%), hypermetabolic ovaries (16%) and uterine (10%) uptake during the ovulatory and menstrual phases during the normal menstrual cycle were identified, and also hypermetabolic brown fat in cold-induced thermogenesis (7%), non-specific bowel uptake (35%) were observed. Among the 147 benign lesions, sequelae of the chest wall and breasts following surgical and/or radiation therapy, were often observed (27%). Hypermetabolic thyroid glands were noted as adenomas and chronic thyroiditis (18%). Reactive hyperplasia of cervical or mediastinal lymph nodes (32%), degenerative osteoarthritis and healed fractures (15%), hypermetabolic benign lung lesions (6%) were observed. Altered physiologic and benign F-18 FDG uptake in the cervical muscle and chest wall following ipsilateral breast surgery or radiotherapy were common, and also normal physiologic uptake in ovary and uterus, brown fat, thyroid were considered as predominant findings in women patients with breast cancer. Knowledge of these findings might aid in the interpretation of FDG PET/CT in patients with breast cancer

  17. The Pneumococcal Serotype 15C Capsule Is Partially O-Acetylated and Allows for Limited Evasion of 23-Valent Pneumococcal Polysaccharide Vaccine-Elicited Anti-Serotype 15B Antibodies

    OpenAIRE

    Spencer, Brady L.; Shenoy, Anukul T.; Orihuela, Carlos J.; Nahm, Moon H.

    2017-01-01

    As a species, Streptococcus pneumoniae (the pneumococcus) utilizes a diverse array of capsular polysaccharides to evade the host. In contrast to large variations in sugar composition and linkage formation, O-acetylation is a subtle capsular modification that nonetheless has a large impact on capsular shielding and recognition of the capsule by vaccine-elicited antibodies. Serotype 15B, which is included in the 23-valent pneumococcal polysaccharide vaccine (PPV23), carries the putative O-acety...

  18. Occurrence of anti-Toxoplasma gondii antibodies in meat and dairy goat herds in Rio Grande do Norte, Brazil.

    Science.gov (United States)

    Medeiros, Andréa Dantas de; Andrade, Milena de Medeiros Clementino; Vítor, Ricardo Wagner de Almeida; Andrade-Neto, Valter Ferreira de

    2014-01-01

    Toxoplasmosis is caused by Toxoplasma gondii, which is the main causative agent of abortion in small ruminants. Goats are among the animals that are most susceptible to this protozoon, and the disease that it causes leads to significant economic losses and has implications for public health, since presence of the parasite in products of goat origin is one of the main sources of human infection. Because of the significant economic impact, there is an urgent need to study the prevalence of T. gondii infection among goats in Sertão do Cabugi, which is the largest goat-producing region in Rio Grande do Norte. In the present study, the ELISA assay was used to test 244 serum samples from nine farms, located in four different municipalities in the Sertão do Cabugi region, which is an important goat-rearing region. The results showed that the prevalence of anti-T. gondii antibodies was 47.1% and that there was a significant association between positivity and the variables of age (≥ 34 months), location (Lajes, Angicos and Afonso Bezerra) and farm (all the farms). The avidity test was applied to all the 115 ELISA-positive samples to distinguish between acute and chronic infection. One hundred and three samples (89.6%) displayed high-avidity antibodies, thus indicating that most of the animals presented chronic infection, with a consequent great impact on the development of the goat production system and a risk to human health.

  19. Occurrence of anti-Toxoplasma gondii antibodies in meat and dairy goat herds in Rio Grande do Norte, Brazil

    Directory of Open Access Journals (Sweden)

    Andréa Dantas de Medeiros

    2014-12-01

    Full Text Available Toxoplasmosis is caused by Toxoplasma gondii, which is the main causative agent of abortion in small ruminants. Goats are among the animals that are most susceptible to this protozoon, and the disease that it causes leads to significant economic losses and has implications for public health, since presence of the parasite in products of goat origin is one of the main sources of human infection. Because of the significant economic impact, there is an urgent need to study the prevalence of T. gondii infection among goats in Sertão do Cabugi, which is the largest goat-producing region in Rio Grande do Norte. In the present study, the ELISA assay was used to test 244 serum samples from nine farms, located in four different municipalities in the Sertão do Cabugi region, which is an important goat-rearing region. The results showed that the prevalence of anti-T. gondii antibodies was 47.1% and that there was a significant association between positivity and the variables of age (≥ 34 months, location (Lajes, Angicos and Afonso Bezerra and farm (all the farms. The avidity test was applied to all the 115 ELISA-positive samples to distinguish between acute and chronic infection. One hundred and three samples (89.6% displayed high-avidity antibodies, thus indicating that most of the animals presented chronic infection, with a consequent great impact on the development of the goat production system and a risk to human health.

  20. Monoclonal antibodies in the treatment of non-Hodgkin's lymphoma.

    Science.gov (United States)

    Fanale, Michelle A; Younes, Anas

    2007-01-01

    resistant to a targeted therapy by activating an alternative pathway to evade apoptosis has driven studies that combine antibodies such as epratuzumab plus rituximab (ER) or ER plus chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) [ER-CHOP], inotuzumab ozogamicin plus rituximab, alemtuzumab plus CHOP (CHOP-C), bevacizumab plus rituximab, and now the combination of rApo2L/TRAIL plus rituximab. As a result of the expansion of research in this area, several treatment-specific adverse effects have been noted, including infusion-related reactions for rituximab, myelosuppression secondary to (90)Y-ibritumomab tiuxetan and (131)I-tositumomab, and immunosuppression leading to infectious complications for alemtuzumab. Also, soluble forms of the antigens (sCD30) are now being investigated as potential mechanisms of resistance to antibody treatments by binding the antibody before the drug can bind to the lymphoma cell. In addition, it has also become apparent that these antibodies often have a dose-dependent half-life (rituximab) or long half-lives of up to 2-3 weeks (epratuzumab and galiximab) with a consequent delay to a response, thus influencing how long we should wait for a response before declaring an antibody to be ineffective. Antibody-based therapeutic approaches have already had a profound impact on the treatment of NHL, and it is almost certain that, as their clinical development progresses, we will continue to refine the optimum methods of incorporating these drugs in NHL treatment in order to offer our patients the best clinical benefits.

  1. Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children's Oncology Group

    International Nuclear Information System (INIS)

    Temple, William; Mendelsohn, Lori; Nekritz, Erin; Gustafson, W.C.; Matthay, Katherine K.; Kim, Grace E.; Lin, Lawrence; Giacomini, Kathy; Naranjo, Arlene; Van Ryn, Collin; Yanik, Gregory A.; Kreissman, Susan G.; Hogarty, Michael; DuBois, Steven G.

    2016-01-01

    Vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2) are thought to mediate MIBG uptake in adult neuroendocrine tumors. In neuroblastoma, the norepinephrine transporter (NET) has been investigated as the principal MIBG uptake protein, though some tumors without NET expression concentrate MIBG. We investigated VMAT expression in neuroblastoma and correlated expression with MIBG uptake and clinical features. We evaluated VMAT1 and VMAT2 expression by immunohistochemistry (IHC) in neuroblastoma tumors from 76 patients with high-risk metastatic disease treated in a uniform cooperative group trial (COG A3973). All patients had baseline MIBG diagnostic scans centrally reviewed. IHC results were scored as the product of intensity grading (0 - 3+) and percent of tumor cells expressing the protein of interest. The association between VMAT1 and VMAT2 scores and clinical and biological features was tested using Wilcoxon rank-sum tests. Patient characteristics were typical of high-risk neuroblastoma, though the cohort was intentionally enriched in patients with MIBG-nonavid tumors (n = 20). VMAT1 and VMAT2 were expressed in 62 % and 75 % of neuroblastoma tumors, respectively. VMAT1 and VMAT2 scores were both significantly lower in MYCN amplified tumors and in tumors with high mitotic karyorrhectic index. MIBG-avid tumors had significantly higher VMAT2 scores than MIBG-nonavid tumors (median 216 vs. 45; p = 0.04). VMAT1 expression did not correlate with MIBG avidity. VMAT1 and VMAT2 are expressed in the majority of neuroblastomas. Expression correlates with other biological features. The expression level of VMAT2 but not that of VMAT1 correlates with avidity for MIBG. (orig.)

  2. Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children's Oncology Group

    Energy Technology Data Exchange (ETDEWEB)

    Temple, William; Mendelsohn, Lori; Nekritz, Erin; Gustafson, W.C.; Matthay, Katherine K. [UCSF School of Medicine, Department of Pediatrics, San Francisco, CA (United States); UCSF Benioff Children' s Hospital, San Francisco, CA (United States); Kim, Grace E. [UCSF School of Medicine, Department of Pathology, San Francisco, CA (United States); Lin, Lawrence; Giacomini, Kathy [UCSF School of Pharmacy, Department of Bioengineering and Therapeutic Sciences, San Francisco, CA (United States); Naranjo, Arlene; Van Ryn, Collin [University of Florida, Children' s Oncology Group Statistics and Data Center, Gainesville, FL (United States); Yanik, Gregory A. [University of Michigan, CS Mott Children' s Hospital, Ann Arbor, MI (United States); Kreissman, Susan G. [Duke University Medical Center, Durham, NC (United States); Hogarty, Michael [University of Pennsylvania, Children' s Hospital of Philadelphia and Perelman School of Medicine, Philadelphia, PA (United States); DuBois, Steven G. [UCSF School of Medicine, Department of Pediatrics, San Francisco, CA (United States); UCSF Benioff Children' s Hospital, San Francisco, CA (United States); UCSF School of Medicine, San Francisco, CA (United States)

    2016-03-15

    Vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2) are thought to mediate MIBG uptake in adult neuroendocrine tumors. In neuroblastoma, the norepinephrine transporter (NET) has been investigated as the principal MIBG uptake protein, though some tumors without NET expression concentrate MIBG. We investigated VMAT expression in neuroblastoma and correlated expression with MIBG uptake and clinical features. We evaluated VMAT1 and VMAT2 expression by immunohistochemistry (IHC) in neuroblastoma tumors from 76 patients with high-risk metastatic disease treated in a uniform cooperative group trial (COG A3973). All patients had baseline MIBG diagnostic scans centrally reviewed. IHC results were scored as the product of intensity grading (0 - 3+) and percent of tumor cells expressing the protein of interest. The association between VMAT1 and VMAT2 scores and clinical and biological features was tested using Wilcoxon rank-sum tests. Patient characteristics were typical of high-risk neuroblastoma, though the cohort was intentionally enriched in patients with MIBG-nonavid tumors (n = 20). VMAT1 and VMAT2 were expressed in 62 % and 75 % of neuroblastoma tumors, respectively. VMAT1 and VMAT2 scores were both significantly lower in MYCN amplified tumors and in tumors with high mitotic karyorrhectic index. MIBG-avid tumors had significantly higher VMAT2 scores than MIBG-nonavid tumors (median 216 vs. 45; p = 0.04). VMAT1 expression did not correlate with MIBG avidity. VMAT1 and VMAT2 are expressed in the majority of neuroblastomas. Expression correlates with other biological features. The expression level of VMAT2 but not that of VMAT1 correlates with avidity for MIBG. (orig.)

  3. Characterization of antibody response in neuroinvasive infection caused by Toscana virus.

    Science.gov (United States)

    Pierro, A; Ficarelli, S; Ayhan, N; Morini, S; Raumer, L; Bartoletti, M; Mastroianni, A; Prati, F; Schivazappa, S; Cenni, P; Vocale, C; Rossini, G; Gaibani, P; Sambri, V; Landini, M P; Lewis, R E; Charrel, R N; Varani, S

    2017-11-01

    Among sandfly-borne pathogens, Toscana virus (TOSV) is a prominent cause of summer meningitis in Mediterranean Europe. Here, we assessed the kinetics of anti-TOSV antibodies over time in 41 patients diagnosed with TOSV meningitis or meningoencephalitis in northeastern Italy. Acute and follow-up serum samples were collected up to 20 months after diagnosis of TOSV infection and tested for the presence of specific antibody using immunoenzymatic and indirect immunofluorescence assays. In addition, maturation of anti-TOSV IgG over time was evaluated as well as production of neutralizing antibodies. Specific IgM and IgG response was present at diagnosis in 100% of patients; TOSV-specific IgM and IgG were detected in patients' sera up to 6 and 20 months after diagnosis, respectively. The avidity index (AI) increased over the first month after infection in 100% of patients and most cases exceeded 60% by Day 30 post infection. The AI subsequently plateaued then declined at 20 months after diagnosis. Finally, neutralization assay to TOSV was performed in 217 sera collected from 41 patients; 69.6% of tested samples resulted in reactive and moderate levels of neutralizing antibodies observed during all phases of infection despite high titres of total anti-TOSV IgG. Specific antibody response develops rapidly and is long-lasting for neuroinvasive TOSV infection. Serodiagnosis of neuroinvasive TOSV requires simultaneous detection of specific IgM and IgG. Moderate levels of neutralizing antibodies were maintained over the study period, while the protective role of antibodies lacking neutralizing activity is unclear and requires further evaluation. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  4. Preparation of monoclonal antibodies against cardiac myosin and some radiolabelling studies

    International Nuclear Information System (INIS)

    Bapat, K.; Venkatesh, M.; Pillai, M.R.A.; Sarma, H.D.; Sainis, K.B.

    1998-01-01

    Monoclonal antibodies were raised against myosin, a specific indicator of myocardial infarction and labelled with 125 I and 99m Tc. Human cardiac myosin was isolated from normal human heart and was used for raising the monoclonal antibodies by the hybridoma technique. Antibody producing clones were identified by ELISA and cloning was done by the limiting dilution technique. Of the 13 clones obtained, 4 were deemed suitable for further studies. The antibodies were grown in ascites, purified, isotyped and their cross reactions with other forms of myosin were estimated. All the clones showed negligible cross reaction with rabbit myosin, but reacted to different extents with bovine skeletal myosin. The most avid antibody Mab-4G4 was chosen for further labelling studies. Mab-4G4 was labelled with 125 I using different oxidising agents such as iodogen, chloramine-T and lactoperoxidase. Purified radioiodinated antibody with radiochemical purity >95% could be obtained by gel filtration. Immunoreactivity was retained as tested by binding to myosin immobilised on a solid support. Mab-4G4 was also labelled with 99m Tc using stannous tartrate as the reducing agent. Radiolabelling yield was ∼60%, the purity was >95% and the immunoreactivity was retained. Both the labelled preparations were tested for bio-distribution in normal and infarcted rats. The activity accumulation in the infarcted region was ∼ 1.5 and 3.5 times as that in normal heart muscle for 125 I and 99m Tc labelled Mab-4G4 respectively. The major problem with the iodinated antibody was the in vivo deiodination resulting in very high percentage of activity in the thyroid. Although the fraction of the total activity associated with the infarcted heart is not very impressive, the fact that the activities with the infarcted and normal hearths are significantly different is heartening. With further optimisation of labelling and use of F(ab)'2 fragments, better delineation of the infarct sites is aspired. (author)

  5. Designer genes. Recombinant antibody fragments for biological imaging

    Energy Technology Data Exchange (ETDEWEB)

    Wu, A.M.; Yazaki, P.J. [Beckman Research Institute of the City of Hope, Duarte, CA (United States). Dept. of Molecular Biology

    2000-09-01

    Monoclonal antibodies (MAbs), with high specificity and high affinity for their target antigens, can be utilized for delivery of agents such as radionuclides, enzymes, drugs or toxins in vivo. However, the implementation of radiolabeled antibodies as magic bullets for detection and treatment of diseases such as cancer has required addressing several shortcomings of murine MAbs. These include their immunogenicity, sub-optimal targeting and pharmacokinetic properties, and practical issues of production and radiolabeling. Genetic engineering provides a powerful approach for redesigning antibodies for use in oncologic applications in vivo. Recombinant fragments have been produced that retain high affinity for target antigens, and display a combination of rapid, high-level tumor targeting with concomitant clearance from normal tissues and the circulation in animal models. An important first step was cloning and engineering of antibody heavy and light chain variable domains into single-chain Fvs (molecular weight, 25-17 kDa), in which the variable regions are joined via a synthetic linker peptide sequence. Although scFvs themselves showed limited tumor uptake in preclinical and clinical studies, they provide a useful building block for intermediate sized recombinant fragments. Covalently linked dimers or non-covalent dimers of scFvs (also known as diabodies) show improved targeting and clearance properties due to their higher molecular weight (55kDa) and increased avidity. Further gains can be made by generation of larger recombinant fragments, such as the minibody, an scFv-C{sub H}3 fusion protein that self-assembles into a bivalent dimer of 80 kDa. A systematic evaluation of scFv, diabody, minibody, and intact antibody (based on comparison of tumor uptakes, tumor: blood activity ratios, and calculation of an Imaging Figure of Merit) can form the basis for selection of combinations of recombinant fragments and radionuclides for imaging applications. Ease of engineering

  6. Designer genes. Recombinant antibody fragments for biological imaging

    International Nuclear Information System (INIS)

    Wu, A.M.; Yazaki, P.J.

    2000-01-01

    Monoclonal antibodies (MAbs), with high specificy and high affinity for their target antigens, can be utilized for delivery of agents such as radionuclides, enzymes, drugs or toxins in vivo. However, the implementation of radiolabeled antibodies as magic bullets for detection and treatment of diseases such as cancer has required addressing several shortcomings of murine MAbs. These include their immunogenicity, sub-optimal targeting and pharmacokinetic properties, and practical issues of production and radiolabeling. Genetic engineering provides a powerful approach for redesigning antibodies for use in oncologic applications in vivo. Recombinant fragments have been produced that retain high affinity for target antigens, and display a combination of rapid, high-level tumor targeting with concomitant clearance from normal tissues and the circulation in animal models. An important first step was cloning and engineering of antibody heavy and light chain variable domains into single-chain Fvs (molecular weight, 25-17 kDa), in which the variable regions are joined via a synthetic linker peptide sequence. Although scFvs themselves showed limited tumor uptake in preclinical and clinical studies, they provide a useful building block for intermediate sized recombinant fragments. Covalently linked dimers or non-covalent dimers of scFvs (also known as diabodies) show improved targeting and clearance properties due to their higher molecular weight (55kDa) and increased avidity. Further gains can be made by generation of larger recombinant fragments, such as the minibody, an scFv-C H 3 fusion protein that self-assembles into a bivalent dimer of 80 kDa. A systematic evaluation of scFv, diabody, minibody, and intact antibody (based on comparison of tumor uptakes, tumor: blood activity ratios, and calculation of an Imaging Figure of Merit) can form the basis for selection of combinations of recombinant fragments and radionuclides for imaging applications. Ease of engineering and

  7. Therapeutic Recombinant Monoclonal Antibodies

    Science.gov (United States)

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  8. Expression of recombinant Antibodies

    Directory of Open Access Journals (Sweden)

    André eFrenzel

    2013-07-01

    Full Text Available Recombinant antibodies are highly specific detection probes in research, diagnostics and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transgenic plants and animals. Currently, almost all therapeutic antibodies are still produced in mammalian cell lines in order to reduce the risk of immunogenicity due to altered, non-human glycosylation patterns. However, recent developments of glycosylation-engineered yeast, insect cell lines and transgenic plants are promising to obtain antibodies with human-like post-translational modifications. Furthermore, smaller antibody fragments including bispecific antibodies without any glycosylation are successfully produced in bacteria and have advanced to clinical testing. The first therapeutic antibody products from a non-mammalian source can be expected in coming next years. In this review, we focus on current antibody production systems including their usability for different applications.

  9. Origin, diversity and maturation of human antiviral antibodies analyzed by high-throughput sequencing

    Directory of Open Access Journals (Sweden)

    Ponraj ePrabakaran

    2012-08-01

    Full Text Available Our understanding of how antibodies are generated and function could help develop effective vaccines and antibody-based therapeutics against viruses such as HIV-1, SARS Coronavirus (CoV, and Hendra and Nipah viruses (henipaviruses. Although broadly neutralizing antibodies (bnAbs against the HIV-1 were observed in patients, elicitation of such bnAbs remains a major challenge when compared to other viral targets. We previously hypothesized that HIV-1 could have evolved a strategy to evade the immune system due to absent or very weak binding of germline antibodies to the conserved epitopes that may not be sufficient to initiate and/or maintain an effective immune response. To further explore our hypothesis, we used the 454 sequence analysis of a large naïve library of human IgM antibodies which had been used for selecting antibodies against SARS Coronavirus (CoV receptor-binding domain (RBD, and soluble G proteins (sG of Hendra and Nipah viruses (henipaviruses. We found that the human IgM repertoires from the 454 sequencing have diverse germline usages, recombination patterns, junction diversity and a lower extent of somatic mutation. In this study, we identified germline intermediates of antibodies specific to HIV-1 and other viruses as observed in normal individuals, and compared their genetic diversity and somatic mutation level along with available structural and functional data. Further computational analysis will provide framework for understanding the underlying genetic and molecular determinants related to maturation pathways of antiviral bnAbs that could be useful for applying novel approaches to the design of effective vaccine immunogens and antibody-based therapeutics.

  10. Antibody engineering: methods and protocols

    National Research Council Canada - National Science Library

    Chames, Patrick

    2012-01-01

    "Antibody Engineering: Methods and Protocols, Second Edition was compiled to give complete and easy access to a variety of antibody engineering techniques, starting from the creation of antibody repertoires and efficient...

  11. What Is Antiphospholipid Antibody Syndrome?

    Science.gov (United States)

    ... Back To Health Topics / Antiphospholipid Antibody Syndrome Antiphospholipid Antibody Syndrome Also known as What Is Antiphospholipid (AN-te-fos-fo-LIP-id) antibody syndrome (APS) is an autoimmune disorder. Autoimmune disorders ...

  12. Synergy of two low-affinity NLSs determines the high avidity of influenza A virus nucleoprotein NP for human importin α isoforms.

    Science.gov (United States)

    Wu, Wei; Sankhala, Rajeshwer S; Florio, Tyler J; Zhou, Lixin; Nguyen, Nhan L T; Lokareddy, Ravi K; Cingolani, Gino; Panté, Nelly

    2017-09-12

    The influenza A virus nucleoprotein (NP) is an essential multifunctional protein that encapsidates the viral genome and functions as an adapter between the virus and the host cell machinery. NPs from all strains of influenza A viruses contain two nuclear localization signals (NLSs): a well-studied monopartite NLS1 and a less-characterized NLS2, thought to be bipartite. Through site-directed mutagenesis and functional analysis, we found that NLS2 is also monopartite and is indispensable for viral infection. Atomic structures of importin α bound to two variants of NLS2 revealed NLS2 primarily binds the major-NLS binding site of importin α, unlike NLS1 that associates with the minor NLS-pocket. Though peptides corresponding to NLS1 and NLS2 bind weakly to importin α, the two NLSs synergize in the context of the full length NP to confer high avidity for importin α7, explaining why the virus efficiently replicates in the respiratory tract that exhibits high levels of this isoform. This study, the first to functionally characterize NLS2, demonstrates NLS2 plays an important and unexpected role in influenza A virus infection. We propose NLS1 and NLS2 form a bipartite NLS in trans, which ensures high avidity for importin α7 while preventing non-specific binding to viral RNA.

  13. Assessment of the diagnostic performance of the IDS-iSYS tests for toxo IgG, toxo IgM and avidity.

    Science.gov (United States)

    Levigne, Pauline; Peyron, François; Wallon, Martine

    2016-10-01

    When acquired during pregnancy toxoplasmosis can have devastating consequences on the fetus. As maternal infection is in the majority of cases subclinical, the diagnosis of toxoplasmosis relies on serological tests for the detection of IgG, IGM and the mesure of IgG avidity. We evaluated the performance of IDS-iSYS a new automatized instrument based on chemiluminescence for the diagnosis of the disease. Our study was based on non-selected samples received in our laboratory either for the determination of serological status or for distinguishing acute from chronic infection. Seven hundred eighty three samples were enrolled in the study. Compared with Architect IgG and IgM assays, the sensitivity and specificity were respectively 99% and 99% for IgG, and 75% and 97% for IgM. We observed higher remaining titers for IDS iSYS IgG, which could reduce the proportions of patients who have to be retested because of doubtful titers. IgM detection and avidity scored equivalent performance with both methods. This automate appears to be a reliable and easy-to-use tool for diagnosing toxoplasmosis in different clinical settings. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. The quantum chemical causality of pMHC-TCR biological avidity: Peptide atomic coordination data and the electronic state of agonist N termini

    Directory of Open Access Journals (Sweden)

    Georgios S.E. Antipas

    2015-06-01

    Full Text Available The quantum state of functional avidity of the synapse formed between a peptide-Major Histocompatibility Complex (pMHC and a T cell receptor (TCR is a subject not previously touched upon. Here we present atomic pair correlation meta-data based on crystalized tertiary structures of the Tax (HTLV-1 peptide along with three artificially altered variants, all of which were presented by the (Class I HLA-A201 protein in complexation with the human (CD8+ A6TCR. The meta-data reveal the existence of a direct relationship between pMHC-TCR functional avidity (agonist/antagonist and peptide pair distribution function (PDF. In this context, antagonist peptides are consistently under-coordinated in respect to Tax. Moreover, Density Functional Theory (DFT datasets in the BLYP/TZ2P level of theory resulting from relaxation of the H species on peptide tertiary structures reveal that the coordination requirement of agonist peptides is also expressed as a physical observable of the protonation state of their N termini: agonistic peptides are always found to retain a stable ammonium (NH3+ terminal group while antagonist peptides are not.

  15. Magnetic resonance imaging after radiofrequency ablation in a rodent model of liver tumor: tissue characterization using a novel necrosis-avid contrast agent

    International Nuclear Information System (INIS)

    Ni, Yicheng; Yu, Jie; Marchal, Guy; Chen, Feng; Mulier, Stefaan; Sun, Xihe; Landuyt, Willy; Verbruggen, Alfons

    2006-01-01

    We exploited a necrosis-avid contrast agent ECIV-7 for magnetic resonance imaging (MRI) in rodent liver tumors after radiofrequency ablation (RFA). Rats bearing liver rhabdomyosarcoma (R1) were randomly allocated to three groups: group I, complete RFA, group II, incomplete RFA, and group III, sham ablation. Within 24 h after RFA, T1-weighted (T1-w) MRI was performed before and after injection of ECIV-7 at 0.05 mmol/kg and followed up from 6-24 h. Signal intensities (SIs) were measured with relative enhancement (RE) and contrast ratio (CR) calculated. The MRI findings were verified histomorphologically. On plain T1-w MRI the contrasts between normal liver, RFA lesion, residual and/or intact tumor were vague. Early after administration of ECIV-7, the liver SI was strongly enhanced (RE=40-50%), leaving the RFA lesion as a hypointense region in groups I and II. At delayed phase, two striking peri-ablational enhancement patterns appeared (RE=90% and CR=1.89%), i.e., ''O'' type of hyperintense rim in group I and ''C'' type of incomplete rim in group II. These MRI manifestations could be proven histologically. In this study, tissue components after RFA could be characterized with discernable contrasts by necrosis-avid contrast agent (NACA)-enhanced MRI, especially at delayed phase. This approach may prove useful for defining the ablated area and identifying residual tumor after RFA. (orig.)

  16. Radiolabelled antibodies in imaging

    International Nuclear Information System (INIS)

    Khaw, B.A.; Haber, E.

    1982-01-01

    Recent technological advances make it possible to produce pure (monoclonal) antibodies in unlimited quantities without the need for continuous immunization of animals and to label these antibodies with a variety of radionuclides which can be traced by single-photon computed tomography. An outline review of the state of the art is presented, with particular reference to the imaging of myocardial infarcts and to tumour imaging studies using labelled monoclonal antibodies (sup(99m)Tc and 125 I). Lengthy bibliography. (U.K.)

  17. The Antibody Response of Pregnant Cameroonian Women to VAR2CSA ID1-ID2a, a Small Recombinant Protein Containing the CSA-Binding Site

    Science.gov (United States)

    Babakhanyan, Anna; Leke, Rose G. F.; Salanti, Ali; Bobbili, Naveen; Gwanmesia, Philomina; Leke, Robert J. I.; Quakyi, Isabella A.; Chen, John J.; Taylor, Diane Wallace

    2014-01-01

    In pregnant women, Plasmodium falciparum-infected erythrocytes expressing the VAR2CSA antigen bind to chondroitin sulfate A in the placenta causing placental malaria. The binding site of VAR2CSA is present in the ID1-ID2a region. This study sought to determine if pregnant Cameroonian women naturally acquire antibodies to ID1-ID2a and if antibodies to ID1-ID2a correlate with absence of placental malaria at delivery. Antibody levels to full-length VAR2CSA and ID1-ID2a were measured in plasma samples from 745 pregnant Cameroonian women, 144 Cameroonian men, and 66 US subjects. IgM levels and IgG avidity to ID1-ID2a were also determined. As expected, antibodies to ID1-ID2a were absent in US controls. Although pregnant Cameroonian women developed increasing levels of antibodies to full-length VAR2CSA during pregnancy, no increase in either IgM or IgG to ID1-ID2a was observed. Surprisingly, no differences in antibody levels to ID1-ID2a were detected between Cameroonian men and pregnant women. For example, in rural settings only 8–9% of males had antibodies to full-length VAR2CSA, but 90–96% had antibodies to ID1-ID2a. In addition, no significant difference in the avidity of IgG to ID1-ID2a was found between pregnant women and Cameroonian men, and no correlation between antibody levels at delivery and absence of placental malaria was found. Thus, the response to ID1-ID2a was not pregnancy specific, but predominantly against cross-reactivity epitopes, which may have been induced by other PfEMP1 antigens, malarial antigens, or microbes. Currently, ID1-ID2a is a leading vaccine candidate, since it binds to the CSA with the same affinity as the full-length molecule and elicits binding-inhibitory antibodies in animals. Further studies are needed to determine if the presence of naturally acquired cross-reactive antibodies in women living in malaria endemic countries will alter the response to ID1-ID2a following vaccination with ID1-ID2a. PMID:24505415

  18. The antibody response of pregnant Cameroonian women to VAR2CSA ID1-ID2a, a small recombinant protein containing the CSA-binding site.

    Directory of Open Access Journals (Sweden)

    Anna Babakhanyan

    Full Text Available In pregnant women, Plasmodium falciparum-infected erythrocytes expressing the VAR2CSA antigen bind to chondroitin sulfate A in the placenta causing placental malaria. The binding site of VAR2CSA is present in the ID1-ID2a region. This study sought to determine if pregnant Cameroonian women naturally acquire antibodies to ID1-ID2a and if antibodies to ID1-ID2a correlate with absence of placental malaria at delivery. Antibody levels to full-length VAR2CSA and ID1-ID2a were measured in plasma samples from 745 pregnant Cameroonian women, 144 Cameroonian men, and 66 US subjects. IgM levels and IgG avidity to ID1-ID2a were also determined. As expected, antibodies to ID1-ID2a were absent in US controls. Although pregnant Cameroonian women developed increasing levels of antibodies to full-length VAR2CSA during pregnancy, no increase in either IgM or IgG to ID1-ID2a was observed. Surprisingly, no differences in antibody levels to ID1-ID2a were detected between Cameroonian men and pregnant women. For example, in rural settings only 8-9% of males had antibodies to full-length VAR2CSA, but 90-96% had antibodies to ID1-ID2a. In addition, no significant difference in the avidity of IgG to ID1-ID2a was found between pregnant women and Cameroonian men, and no correlation between antibody levels at delivery and absence of placental malaria was found. Thus, the response to ID1-ID2a was not pregnancy specific, but predominantly against cross-reactivity epitopes, which may have been induced by other PfEMP1 antigens, malarial antigens, or microbes. Currently, ID1-ID2a is a leading vaccine candidate, since it binds to the CSA with the same affinity as the full-length molecule and elicits binding-inhibitory antibodies in animals. Further studies are needed to determine if the presence of naturally acquired cross-reactive antibodies in women living in malaria endemic countries will alter the response to ID1-ID2a following vaccination with ID1-ID2a.

  19. Felix Hoppe-Seyler Lecture 1997. Protective antibody responses against viruses.

    Science.gov (United States)

    Zinkernagel, R M

    1997-08-01

    Neutralizing antibody responses against the acute cytopathic vesicular stomatitis virus (VSV) have been studied in mice to evaluate their general characteristics including specificity, self-/non-self discrimination and memory. IgM responses are generated very early, by day 3 to 4, in a T helper cell-independent fashion and without VSV having polyclonal activating capacities. The order of the glycoprotein tips on the virus envelope (multiple, 8-10 nm distance, paracrystalline) exhibiting the neutralizing determinants are key to this prompt response. These paracrystalline identical multimeric antigens are characteristic of infectious agents and are always reacted against by B cells. Self-antigens that are accessible to B cells in the intact host are either monomeric in serum or mobile multimers on cell surfaces; these configurations need contact dependent or contact independent T help, respectively. Because T help is tolerant against self-antigens, no anti-self B cell responses are usually induced against monomeric self-antigens. If collagen or DNA (rigid multimeric self-antigens) become accessible, however, they may become targets of auto-antibody responses. The antibody repertoire against VSV is partially contained in the germline and partially is generated by somatic mutation; they seem not to undergo affinity-maturation. In any case protection against lethal infection is dependent upon strictly T helper cell dependent IgG generated by day 6 to 7 and reaches a protective level of about 1-10 micrograms/ml. Interesting affinity/avidity and onrate above a minimal threshold are of no apparent advantage for protection in vivo. Maintenance of these antibody levels by antigen depots, and not the presence of memory B cells alone, is key to providing protective immunological memory. Collectively these data suggest that studying biologically important protective antibody responses may modify some of the parameters that have been defined by studying hapten specific antibody

  20. Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16

    Energy Technology Data Exchange (ETDEWEB)

    Pancera, Marie; Shahzad-ul-Hussan, Syed; Doria-Rose, Nicole A.; McLellan, Jason S.; Bailer, Robert T.; Dai, Kaifan; Loesgen, Sandra; Louder, Mark K.; Staupe, Ryan P.; Yang, Yongping; Zhang, Baoshan; Parks, Robert; Eudailey, Joshua; Lloyd, Krissey E.; Blinn, Julie; Alam, S. Munir; Haynes, Barton F.; Amin, Mohammed N.; Wang, Lai-Xi; Burton, Dennis R.; Koff, Wayne C.; Nabel, Gary J.; Mascola, John R.; Bewley, Carole A; Kwong, Peter D. [NIH; (Scripps); (Duke); (Maryland-MED); (IAVI)

    2013-08-05

    HIV-1 uses a diverse N-linked-glycan shield to evade recognition by antibody. Select human antibodies, such as the clonally related PG9 and PG16, recognize glycopeptide epitopes in the HIV-1 V1–V2 region and penetrate this shield, but their ability to accommodate diverse glycans is unclear. Here we report the structure of antibody PG16 bound to a scaffolded V1–V2, showing an epitope comprising both high mannose–type and complex-type N-linked glycans. We combined structure, NMR and mutagenesis analyses to characterize glycan recognition by PG9 and PG16. Three PG16-specific residues, arginine, serine and histidine (RSH), were critical for binding sialic acid on complex-type glycans, and introduction of these residues into PG9 produced a chimeric antibody with enhanced HIV-1 neutralization. Although HIV-1–glycan diversity facilitates evasion, antibody somatic diversity can overcome this and can provide clues to guide the design of modified antibodies with enhanced neutralization.

  1. Monoclonal antibodies in oncology

    International Nuclear Information System (INIS)

    Chan, S.Y.T.; Sikora, K.

    1986-01-01

    Monoclonal antibodies (MCAs) can be used to differentiate between normal and neoplastic cells and thus exploited for diagnostic and, ultimately, therapeutic gain. The evidence for the existence of human tumour antigens is reviewed. Several areas of diagnosis are already benefiting from the application of the monoclonal technology. Immunohistology can help the pathologist with difficult diagnostic problems. New classifications of lymphoma and leukaemia can be based on specific surface molecules. Similarly, the detection of shed tumour antigens is already established as part of the routine assessment of many patients with common solid tumours. Isotopically labeled monoclonal antibodies have been used to localise primary and metastatic tumours. The use of antibodies in this way is not only a promising diagnostic tool but also the first step in studying the possibility of arming antibodies to provide therapeutic agents. Such trials are currently in progress. (Auth.)

  2. Future of antibody purification.

    Science.gov (United States)

    Low, Duncan; O'Leary, Rhona; Pujar, Narahari S

    2007-03-15

    Antibody purification seems to be safely ensconced in a platform, now well-established by way of multiple commercialized antibody processes. However, natural evolution compels us to peer into the future. This is driven not only by a large, projected increase in the number of antibody therapies, but also by dramatic improvements in upstream productivity, and process economics. Although disruptive technologies have yet escaped downstream processes, evolution of the so-called platform is already evident in antibody processes in late-stage development. Here we perform a wide survey of technologies that are competing to be part of that platform, and provide our [inherently dangerous] assessment of those that have the most promise.

  3. Serum herpes simplex antibodies

    Science.gov (United States)

    ... causes cold sores (oral herpes). HSV-2 causes genital herpes. How the Test is Performed A blood sample ... person has ever been infected with oral or genital herpes . It looks for antibodies to herpes simplex virus ...

  4. Antibody tumor penetration

    Science.gov (United States)

    Thurber, Greg M.; Schmidt, Michael M.; Wittrup, K. Dane

    2009-01-01

    Antibodies have proven to be effective agents in cancer imaging and therapy. One of the major challenges still facing the field is the heterogeneous distribution of these agents in tumors when administered systemically. Large regions of untargeted cells can therefore escape therapy and potentially select for more resistant cells. We present here a summary of theoretical and experimental approaches to analyze and improve antibody penetration in tumor tissue. PMID:18541331

  5. Detection of antibodies to bacterial cell wall peptidoglycan in human sera

    International Nuclear Information System (INIS)

    Heymer, B.; Schleifer, K.H.; Read, S.; Zabriskie, J.B.; Krause, R.M.

    1976-01-01

    A radioimmunoassay has been developed for the measurement of antibodies to peptidoglycan in human sera including patients with rheumatic feaver and juvenile rheumatoid arthritis. The assay is based on the percentage of binding of the hapten 125 I-L-Ala-γ-D-Glu-L-Lys-D-Ala-D-Ala, the major peptide determinant of peptidoglycan. Because of differences in the avidity of the antibodies in different sera, the amount of antibody was expressed as pentapeptide hapten-binding capacity (pentapeptide-HBC in ng/ml of serum). Fourteen out of 105 normal blood donors had a pentapeptide-HBC value greater than or equal to 75 ng/ml serum. Values in healthy children 5 to 18 years of age were less than or equal to 50 ng/ml. Sixty-eight percent of the individuals with rheumatic fever had values greater than or equal to 75 ng/ml, an indication that streptococcal infections can stimulate an immune response to peptidoglycan. Thirty-five percent of the patients with juvenile rheumatoid arthritis had values greater than or equal to 75 ng/ml. Such a finding points to a possible association between bacterial infections and juvenile rheumatoid arthritis

  6. {sup 18}F-FDG-Avid Adenocarcinoma of the Rectum Presenting as a Subtle Filling Defect on Maximum Intensity Projection Image: Report of a Case

    Energy Technology Data Exchange (ETDEWEB)

    Bahk, Yong Whee; Lee, Kwang Chan [SungAe General Hospital, Seoul (Korea, Republic of)

    2009-04-15

    {sup 18}F-FDG avid polypoid or tumefacient carcinomas of the gastrointestinal (GI) tract including the rectum are characteristically featured on PET-CT as an intraluminal tumor surrounded by completely or partially cleared background. However, the carcinomas of intramural or sessile variant may not so easily be detected especially when tumors are obliterated by feces or mucus retained in the host bowel loop. Recently, we observed a case of cauliflower-like adenocarcinoma of the rectum that was diagnosed by noting a subtle, flat filling defect created against the background of 'black' feces-mucus filled rectum. To our knowledge such a 'filling defect' produced by sessile tumor has not previously been reported as a useful diagnostic sign of GI tract carcinoma on PET-CT.

  7. Duration of 18F-FDG avidity in lymph nodes after pandemic H1N1v and seasonal influenza vaccination

    International Nuclear Information System (INIS)

    Thomassen, Anders; Lerberg Nielsen, Anne; Gerke, Oke; Johansen, Allan; Petersen, Henrik

    2011-01-01

    The aim of our study was to investigate the occurrence of fluorodeoxyglucose (FDG) avidity in draining axillary lymph nodes after vaccination against influenza (H1N1v pandemic and seasonal) and to determine the period of increased FDG uptake. During December 2009, patients referred for 18 F-FDG positron emission tomography (PET)/CT scans (n = 293) filled in a questionnaire concerning vaccination type (seasonal and/or H1N1v), time and anatomical localization of vaccination. Only injections in deltoid regions were evaluated, thus ensuring that draining lymph nodes were axillary. If more vaccinations had been given, only the latest vaccination was evaluated in each deltoid region. Of all patients who underwent PET/CT scans during December 2009, 26% had been vaccinated with at least one influenza vaccination in the deltoid region. A total of 92 'draining' and 60 'reference' (i.e. contralateral, non-vaccinated) axillary lymph nodes were evaluated in 61 patients (19 of 61 patients were scanned twice). The maximal intensity in FDG uptake (SUV max ) in draining lymph nodes was 5 g/ml body weight (BW), whereas the maximal intensity in reference lymph nodes was 1.9 g/ml BW. The SUV max was normalized approximately 40 days after vaccination. No significant enlargement of metabolically active draining lymph nodes could be demonstrated on CT scan. Chemotherapy or immunosuppressive drugs given within 2 weeks from vaccination did not affect SUV max in the axillary lymph nodes. Influenza vaccination may lead to FDG-avid draining lymph nodes beyond 1 month. (orig.)

  8. Duration of {sup 18}F-FDG avidity in lymph nodes after pandemic H1N1v and seasonal influenza vaccination

    Energy Technology Data Exchange (ETDEWEB)

    Thomassen, Anders; Lerberg Nielsen, Anne; Gerke, Oke; Johansen, Allan; Petersen, Henrik [OUH, Odense University Hospital, Department of Nuclear Medicine, Odense C (Denmark)

    2011-05-15

    The aim of our study was to investigate the occurrence of fluorodeoxyglucose (FDG) avidity in draining axillary lymph nodes after vaccination against influenza (H1N1v pandemic and seasonal) and to determine the period of increased FDG uptake. During December 2009, patients referred for {sup 18}F-FDG positron emission tomography (PET)/CT scans (n = 293) filled in a questionnaire concerning vaccination type (seasonal and/or H1N1v), time and anatomical localization of vaccination. Only injections in deltoid regions were evaluated, thus ensuring that draining lymph nodes were axillary. If more vaccinations had been given, only the latest vaccination was evaluated in each deltoid region. Of all patients who underwent PET/CT scans during December 2009, 26% had been vaccinated with at least one influenza vaccination in the deltoid region. A total of 92 'draining' and 60 'reference' (i.e. contralateral, non-vaccinated) axillary lymph nodes were evaluated in 61 patients (19 of 61 patients were scanned twice). The maximal intensity in FDG uptake (SUV{sub max}) in draining lymph nodes was 5 g/ml body weight (BW), whereas the maximal intensity in reference lymph nodes was 1.9 g/ml BW. The SUV{sub max} was normalized approximately 40 days after vaccination. No significant enlargement of metabolically active draining lymph nodes could be demonstrated on CT scan. Chemotherapy or immunosuppressive drugs given within 2 weeks from vaccination did not affect SUV{sub max} in the axillary lymph nodes. Influenza vaccination may lead to FDG-avid draining lymph nodes beyond 1 month. (orig.)

  9. Multivalent Soluble Antigen Arrays Exhibit High Avidity Binding and Modulation of B Cell Receptor-Mediated Signaling to Drive Efficacy against Experimental Autoimmune Encephalomyelitis.

    Science.gov (United States)

    Hartwell, Brittany L; Pickens, Chad J; Leon, Martin; Berkland, Cory

    2017-06-12

    A pressing need exists for antigen-specific immunotherapies (ASIT) that induce selective tolerance in autoimmune disease while avoiding deleterious global immunosuppression. Multivalent soluble antigen arrays (SAgA PLP:LABL ), consisting of a hyaluronic acid (HA) linear polymer backbone cografted with multiple copies of autoantigen (PLP) and cell adhesion inhibitor (LABL) peptides, are designed to induce tolerance to a specific multiple sclerosis (MS) autoantigen. Previous studies established that hydrolyzable SAgA PLP:LABL , employing a degradable linker to codeliver PLP and LABL, was therapeutic in experimental autoimmune encephalomyelitis (EAE) in vivo and exhibited antigen-specific binding with B cells, targeted the B cell receptor (BCR), and dampened BCR-mediated signaling in vitro. Our results pointed to sustained BCR engagement as the SAgA PLP:LABL therapeutic mechanism, so we developed a new version of the SAgA molecule using nonhydrolyzable conjugation chemistry, hypothesizing it would enhance and maintain the molecule's action at the cell surface to improve efficacy. "Click SAgA" (cSAgA PLP:LABL ) uses hydrolytically stable covalent conjugation chemistry (Copper-catalyzed Azide-Alkyne Cycloaddition (CuAAC)) rather than a hydrolyzable oxime bond to attach PLP and LABL to HA. We explored cSAgA PLP:LABL B cell engagement and modulation of BCR-mediated signaling in vitro through flow cytometry binding and calcium flux signaling assays. Indeed, cSAgA PLP:LABL exhibited higher avidity B cell binding and greater dampening of BCR-mediated signaling than hydrolyzable SAgA PLP:LABL . Furthermore, cSAgA PLP:LABL exhibited significantly enhanced in vivo efficacy compared to hydrolyzable SAgA PLP:LABL , achieving equivalent efficacy at one-quarter of the dose. These results indicate that nonhydrolyzable conjugation increased the avidity of cSAgA PLP:LABL to drive in vivo efficacy through modulated BCR-mediated signaling.

  10. Radiolabelled antibody imaging

    International Nuclear Information System (INIS)

    Perkins, A.C.

    1986-01-01

    A steadily growing number of tumor-associated antigens are used to raise antibodies used for the detection of human tumors by external imaging, a technique termed immunoscintigraphy. The majority of these clinical antibody studies are performed using Iodine-131, which is cheap, readily available and easily attached to protein. It has the disadvantage of having a high energy gamma emission (365 keV) which is poorly detected by modern cameras, so that increasing use is now being made of more appropriate labels with lower energies for imaging, such as Iodine-123, Indium-111 and Technetium-99m. A number of research centres in the United Kingdom are currently involved in the production of tumor-associated monoclonal antibodies, only a small number of which are finally selected for diagnostic use. These developments represent a major area of advancement in Nuclear Medicine and when used for imaging are capable of providing diagnostic information complimentary to other diagnostic techniques

  11. Antibody informatics for drug discovery

    DEFF Research Database (Denmark)

    Shirai, Hiroki; Prades, Catherine; Vita, Randi

    2014-01-01

    to the antibody science in every project in antibody drug discovery. Recent experimental technologies allow for the rapid generation of large-scale data on antibody sequences, affinity, potency, structures, and biological functions; this should accelerate drug discovery research. Therefore, a robust bioinformatic...... infrastructure for these large data sets has become necessary. In this article, we first identify and discuss the typical obstacles faced during the antibody drug discovery process. We then summarize the current status of three sub-fields of antibody informatics as follows: (i) recent progress in technologies...... for antibody rational design using computational approaches to affinity and stability improvement, as well as ab-initio and homology-based antibody modeling; (ii) resources for antibody sequences, structures, and immune epitopes and open drug discovery resources for development of antibody drugs; and (iii...

  12. The POM monoclonals: a comprehensive set of antibodies to non-overlapping prion protein epitopes.

    Directory of Open Access Journals (Sweden)

    Magdalini Polymenidou

    Full Text Available PrP(Sc, a misfolded and aggregated form of the cellular prion protein PrP(C, is the only defined constituent of the transmissible agent causing prion diseases. Expression of PrP(C in the host organism is necessary for prion replication and for prion neurotoxicity. Understanding prion diseases necessitates detailed structural insights into PrP(C and PrP(Sc. Towards this goal, we have developed a comprehensive collection of monoclonal antibodies denoted POM1 to POM19 and directed against many different epitopes of mouse PrP(C. Three epitopes are located within the N-terminal octarepeat region, one is situated within the central unstructured region, and four epitopes are discontinuous within the globular C-proximal domain of PrP(C. Some of these antibodies recognize epitopes that are resilient to protease digestion in PrP(Sc. Other antibodies immunoprecipitate PrP(C, but not PrP(Sc. A third group was found to immunoprecipitate both PrP isoforms. Some of the latter antibodies could be blocked with epitope-mimicking peptides, and incubation with an excess of these peptides allowed for immunochromatography of PrP(C and PrP(Sc. Amino-proximal antibodies were found to react with repetitive PrP(C epitopes, thereby vastly increasing their avidity. We have also created functional single-chain miniantibodies from selected POMs, which retained the binding characteristics despite their low molecular mass. The POM collection, thus, represents a unique set of reagents allowing for studies with a variety of techniques, including western blotting, ELISA, immunoprecipitation, conformation-dependent immunoassays, and plasmon surface plasmon resonance-based assays.

  13. Antithyroglobulin Antibodies and Antimicrosomal Antibodies in Various Thyroid Diseases

    International Nuclear Information System (INIS)

    Lee, Gwon Jun; Hong, Key Sak; Choi, Kang Won; Lee, Kyu; Koh, Chang Soon; Lee, Mun Ho; Park, Sung Hoe; Chi, Je Geun; Lee, Sang Kook

    1979-01-01

    The authors investigated the incidence of antithyroglobulin antibodies and antibodies and antimicrosomal antibodies measured by tanned red cell hemagglutination method in subjects suffering from various thyroid disorders. 1) In 15 normal patients, neither suffering from any thyroid diseases nor from any other autoimmune disorders, the antithyroglobulin antibodies were all negative, but the antimicrosomal antibody was positive only in one patient (6.7%). 2) The antithyroglobulin antibodies were positive in 31.5% (34 patients) of 108 patients with various thyroid diseases, and the antimicrosomal antibodies were positive in 37.0% (40 patients). 3) of the 25 patients with Graves' diseases, 7 patients (28.0%) showed positive for the antithyroglobulin antibodies, and 9 (36.0%) for the antimicrosomal antibodies. There was no definite differences in clinical and thyroid functions between the groups with positive and negative results. 4) Both antibodies were positive in 16 (88.9%) and 17 (94.4%) patients respectively among 18 patients with Hashimoto's thyroiditis, all of them were diagnosed histologically. 5) Three out of 33 patients with thyroid adenoma showed positive antibodies, and 3 of 16 patients with thyroid carcinoma revealed positive antibodies. 6) TRCH antibodies demonstrated negative results in 2 patients with subacute thyroiditis, but positive in one patient with idiopathic primary myxedema. 7) The number of patients with high titers(>l:802) was 16 for antithyroglobulin antibody, and 62.5% (10 patients) of which was Hashimoto's thyroiditis. Thirteen (65.0) of 20 patients with high titers (>l:802) for antimicrosomal antibody was Hashimoto's thyroiditis. TRCH test is a simple, sensitive method, and has high reliability and reproducibility. The incidences and titers of antithyroglobulin antibody and antimicrosomal antibody are especially high in Hashimoto's thyroiditis.

  14. Antithyroglobulin Antibodies and Antimicrosomal Antibodies in Various Thyroid Diseases

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Gwon Jun; Hong, Key Sak; Choi, Kang Won; Lee, Kyu; Koh, Chang Soon; Lee, Mun Ho; Park, Sung Hoe; Chi, Je Geun; Lee, Sang Kook [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1979-03-15

    The authors investigated the incidence of antithyroglobulin antibodies and antibodies and antimicrosomal antibodies measured by tanned red cell hemagglutination method in subjects suffering from various thyroid disorders. 1) In 15 normal patients, neither suffering from any thyroid diseases nor from any other autoimmune disorders, the antithyroglobulin antibodies were all negative, but the antimicrosomal antibody was positive only in one patient (6.7%). 2) The antithyroglobulin antibodies were positive in 31.5% (34 patients) of 108 patients with various thyroid diseases, and the antimicrosomal antibodies were positive in 37.0% (40 patients). 3) of the 25 patients with Graves' diseases, 7 patients (28.0%) showed positive for the antithyroglobulin antibodies, and 9 (36.0%) for the antimicrosomal antibodies. There was no definite differences in clinical and thyroid functions between the groups with positive and negative results. 4) Both antibodies were positive in 16 (88.9%) and 17 (94.4%) patients respectively among 18 patients with Hashimoto's thyroiditis, all of them were diagnosed histologically. 5) Three out of 33 patients with thyroid adenoma showed positive antibodies, and 3 of 16 patients with thyroid carcinoma revealed positive antibodies. 6) TRCH antibodies demonstrated negative results in 2 patients with subacute thyroiditis, but positive in one patient with idiopathic primary myxedema. 7) The number of patients with high titers(>l:802) was 16 for antithyroglobulin antibody, and 62.5% (10 patients) of which was Hashimoto's thyroiditis. Thirteen (65.0) of 20 patients with high titers (>l:802) for antimicrosomal antibody was Hashimoto's thyroiditis. TRCH test is a simple, sensitive method, and has high reliability and reproducibility. The incidences and titers of antithyroglobulin antibody and antimicrosomal antibody are especially high in Hashimoto's thyroiditis.

  15. Prediction of Antibody Epitopes

    DEFF Research Database (Denmark)

    Nielsen, Morten; Marcatili, Paolo

    2015-01-01

    Antibodies recognize their cognate antigens in a precise and effective way. In order to do so, they target regions of the antigenic molecules that have specific features such as large exposed areas, presence of charged or polar atoms, specific secondary structure elements, and lack of similarity...... to self-proteins. Given the sequence or the structure of a protein of interest, several methods exploit such features to predict the residues that are more likely to be recognized by an immunoglobulin.Here, we present two methods (BepiPred and DiscoTope) to predict linear and discontinuous antibody...

  16. Antibody affinity maturation

    DEFF Research Database (Denmark)

    Skjødt, Mette Louise

    Yeast surface display is an effective tool for antibody affinity maturation because yeast can be used as an all-in-one workhorse to assemble, display and screen diversified antibody libraries. By employing the natural ability of yeast Saccharomyces cerevisiae to efficiently recombine multiple DNA...... laboratory conditions. A particular emphasis was put on using molecular techniques in conjunction with microenvironmental measurements (O2, pH, irradiance), a combination that is rarely found but provides a much more detailed understanding of “cause and effect” in complex natural systems...

  17. Compositions, antibodies, asthma diagnosis methods, and methods for preparing antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Hongjun; Zangar, Richard C.

    2017-01-17

    Methods for preparing an antibody are provided with the method including incorporating 3-bromo-4-hydroxy-benzoic acid into a protein to form an antigen, immunizing a mammalian host with the antigen, and recovering an antibody having an affinity for the antigen from the host. Antibodies having a binding affinity for a monohalotyrosine are provided as well as composition comprising an antibody bound with monohalotyrosine. Compositions comprising a protein having a 3-bromo-4-hydroxy-benzoic acid moiety are also provided. Methods for evaluating the severity of asthma are provide with the methods including analyzing sputum of a patient using an antibody having a binding affinity for monohalotyrosine, and measuring the amount of antibody bound to protein. Methods for determining eosinophil activity in bodily fluid are also provided with the methods including exposing bodily fluid to an antibody having a binding affinity for monohalotyrosine, and measuring the amount of bound antibody to determine the eosinophil activity.

  18. Prediction of antibody persistency from antibody titres to natalizumab

    DEFF Research Database (Denmark)

    Jensen, Poul Erik H; Koch-Henriksen, Nils; Sellebjerg, Finn

    2012-01-01

    In a subgroup of patients with multiple sclerosis natalizumab therapy causes generation of anti-natalizumab antibodies that may be transient or persistent. It is recommended to discontinue natalizumab therapy in persistently antibody-positive patients.......In a subgroup of patients with multiple sclerosis natalizumab therapy causes generation of anti-natalizumab antibodies that may be transient or persistent. It is recommended to discontinue natalizumab therapy in persistently antibody-positive patients....

  19. Human monoclonal antibodies: the residual challenge of antibody immunogenicity.

    Science.gov (United States)

    Waldmann, Herman

    2014-01-01

    One of the major reasons for seeking human monoclonal antibodies has been to eliminate immunogenicity seen with rodent antibodies. Thus far, there has yet been no approach which absolutely abolishes that risk for cell-binding antibodies. In this short article, I draw attention to classical work which shows that monomeric immunoglobulins are intrinsically tolerogenic if they can be prevented from creating aggregates or immune complexes. Based on these classical studies two approaches for active tolerization to therapeutic antibodies are described.

  20. ANA (Antinuclear Antibody Test)

    Science.gov (United States)

    ... as ratios. For example, the result 1:320 means that one part blood sample was mixed with 320 parts of a diluting ... name "antinuclear". My doctor told me my ANA test is ... normal concentration of these antibodies. This is one of the tools in diagnosing lupus as well ...

  1. Monoclonal antibodies in myeloma

    DEFF Research Database (Denmark)

    Sondergeld, P.; van de Donk, N. W. C. J.; Richardson, P. G.

    2015-01-01

    The development of monoclonal antibodies (mAbs) for the treatment of disease goes back to the vision of Paul Ehrlich in the late 19th century; however, the first successful treatment with a mAb was not until 1982, in a lymphoma patient. In multiple myeloma, mAbs are a very recent and exciting add...

  2. Antibodies Targeting EMT

    Science.gov (United States)

    2017-10-01

    these unusual antibodies can effectively be displayed on the cell surface. 5 Additionally, we successfully prepared cDNA from lymphocytes derived...from cow peripheral blood, spleen, and lymph nodes, amplified this cDNA by PCR with VH gene specific primers, and this “library” has been cloned into

  3. Antibody Blood Tests

    Science.gov (United States)

    ... out for sure? If antibody tests and/or symptoms suggest celiac disease, the physician needs to establish the diagnosis by ... who is still experiencing symptoms, to establish the diagnosis or to rule out celiac disease as a part of establishing another diagnosis. Find ...

  4. Antinuclear Antibodies (ANA)

    Science.gov (United States)

    ... MACRA MACRAlerts MACRA FAQs MACRA Glossary MACRA Resources Position Statements Insurance Advocacy Current Issues Tools & Resources Practice Resources ... a medical or health condition. Resources Antinuclear Antibodies (ANA) in Spanish (Español) Download Print-Friendly PDF ... Join Donate © 2018 American College ...

  5. Next Generation Antibody Therapeutics Using Bispecific Antibody Technology.

    Science.gov (United States)

    Igawa, Tomoyuki

    2017-01-01

    Nearly fifty monoclonal antibodies have been approved to date, and the market for monoclonal antibodies is expected to continue to grow. Since global competition in the field of antibody therapeutics is intense, we need to establish novel antibody engineering technologies to provide true benefit for patients, with differentiated product values. Bispecific antibodies are among the next generation of antibody therapeutics that can bind to two different target antigens by the two arms of immunoglobulin G (IgG) molecule, and are thus believed to be applicable to various therapeutic needs. Until recently, large scale manufacturing of human IgG bispecific antibody was impossible. We have established a technology, named asymmetric re-engineering technology (ART)-Ig, to enable large scale manufacturing of bispecific antibodies. Three examples of next generation antibody therapeutics using ART-Ig technology are described. Recent updates on bispecific antibodies against factor IXa and factor X for the treatment of hemophilia A, bispecific antibodies against a tumor specific antigen and T cell surface marker CD3 for cancer immunotherapy, and bispecific antibodies against two different epitopes of soluble antigen with pH-dependent binding property for the elimination of soluble antigen from plasma are also described.

  6. Anti-smooth muscle antibody

    Science.gov (United States)

    ... gov/ency/article/003531.htm Anti-smooth muscle antibody To use the sharing features on this page, please enable JavaScript. Anti-smooth muscle antibody is a blood test that detects the presence ...

  7. Tabhu: tools for antibody humanization.

    KAUST Repository

    Olimpieri, Pier Paolo; Marcatili, Paolo; Tramontano, Anna

    2014-01-01

    for antibody humanization. Tabhu includes tools for human template selection, grafting, back-mutation evaluation, antibody modelling and structural analysis, helping the user in all the critical steps of the humanization experiment protocol. AVAILABILITY: http

  8. Salmonella Typhi Colonization Provokes Extensive Transcriptional Changes Aimed at Evading Host Mucosal Immune Defense During Early Infection of Human Intestinal Tissue

    Directory of Open Access Journals (Sweden)

    K.P. Nickerson

    2018-05-01

    Full Text Available Commensal microorganisms influence a variety of host functions in the gut, including immune response, glucose homeostasis, metabolic pathways and oxidative stress, among others. This study describes how Salmonella Typhi, the pathogen responsible for typhoid fever, uses similar strategies to escape immune defense responses and survive within its human host. To elucidate the early mechanisms of typhoid fever, we performed studies using healthy human intestinal tissue samples and “mini-guts,” organoids grown from intestinal tissue taken from biopsy specimens. We analyzed gene expression changes in human intestinal specimens and bacterial cells both separately and after colonization. Our results showed mechanistic strategies that S. Typhi uses to rearrange the cellular machinery of the host cytoskeleton to successfully invade the intestinal epithelium, promote polarized cytokine release and evade immune system activation by downregulating genes involved in antigen sampling and presentation during infection. This work adds novel information regarding S. Typhi infection pathogenesis in humans, by replicating work shown in traditional cell models, and providing new data that can be applied to future vaccine development strategies. Keywords: Typhoid fever, Salmonella, Snapwell™ system, Human tissue, Terminal ileum, Immune system, Innate immunity, Immune evasion, Host-pathogen interaction, Vaccine development, Intestinal organoids, Organoid monolayer

  9. Cross-border reproductive care for law evasion: should physicians be allowed to help infertility patients evade the law of their own country?

    Science.gov (United States)

    Van Hoof, Wannes; Pennings, Guido; De Sutter, Petra

    2016-07-01

    There are fundamental differences between countries with regard to legislation on assisted reproduction. Many infertility patients are looking to evade the law of their own country and make use of reproductive services abroad. The role of the local physician in cross-border reproductive care for law evasion has been characterized as "channeling local patients to foreign medical establishments" and "against the spirit and essence of the law". The logical view is that by supporting CBRC for law evasion, physicians are essentially supporting immoral behavior. We will tackle this position on two levels. First, we will argue that governments should generally be tolerant toward people with different positions on assisted reproduction. Second, we will show that contributing to cross-border reproductive care for law evasion is not necessarily immoral, because the prima facie wrongness of complicity in law evasion can be outweighed by the fact that physicians should act in the best interest of the patient. Several countries have tried to prevent local physicians from helping patients to make use of reproductive services abroad, but they should rather leave it up to the individual physicians to decide whether or not to support a particular patient. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Antibodies from plants for bionanomaterials

    OpenAIRE

    Edgue, G.; Twyman, R.M.; Beiss, V.; Fischer, R.; Sack, M.

    2017-01-01

    Antibodies are produced as part of the vertebrate adaptive immune response and are not naturally made by plants. However, antibody DNA sequences can be introduced into plants, and together with laboratory technologies that allow the design of antibodies recognizing any conceivable molecular structure, plants can be used as green factories' to produce any antibody at all. The advent of plant-based transient expression systems in particular allows the rapid, convenient, and safe production of a...

  11. Synthetic peptides for antibody production

    NARCIS (Netherlands)

    Zegers, N.D.

    1995-01-01

    Synthetic peptides are useful tools for the generation of antibodies. The use of antibodies as specific reagents in inununochemical assays is widely applied. In this chapter, the application of synthetic peptides for the generation of antibodies is described. The different steps that lead to the

  12. Synthetic peptides for antibody production

    NARCIS (Netherlands)

    N.D. Zegers (Netty)

    1995-01-01

    textabstractSynthetic peptides are useful tools for the generation of antibodies. The use of antibodies as specific reagents in inununochemical assays is widely applied. In this chapter, the application of synthetic peptides for the generation of antibodies is described. The different steps

  13. Monoclonal antibodies to Pneumocystis carinii

    DEFF Research Database (Denmark)

    Kovacs, J A; Halpern, J L; Lundgren, B

    1989-01-01

    To increase understanding of the antigenic structure of Pneumocystis carinii, we developed monoclonal antibodies to rat and human P. carinii. The specificity of the antibodies was demonstrated by immunofluorescence and immunoblot studies. Only one of five monoclonal antibodies to rat P. carinii r...

  14. Antibody mimetics: promising complementary agents to animal-sourced antibodies.

    Science.gov (United States)

    Baloch, Abdul Rasheed; Baloch, Abdul Wahid; Sutton, Brian J; Zhang, Xiaoying

    2016-01-01

    Despite their wide use as therapeutic, diagnostic and detection agents, the limitations of polyclonal and monoclonal antibodies have inspired scientists to design the next generation biomedical agents, so-called antibody mimetics that offer many advantages over conventional antibodies. Antibody mimetics can be constructed by protein-directed evolution or fusion of complementarity-determining regions through intervening framework regions. Substantial progress in exploiting human, butterfly (Pieris brassicae) and bacterial systems to design and select mimetics using display technologies has been made in the past 10 years, and one of these mimetics [Kalbitor® (Dyax)] has made its way to market. Many challenges lie ahead to develop mimetics for various biomedical applications, especially those for which conventional antibodies are ineffective, and this review describes the current characteristics, construction and applications of antibody mimetics compared to animal-sourced antibodies. The possible limitations of mimetics and future perspectives are also discussed.

  15. Intraoperative detection of 18F-FDG-avid tissue sites using the increased probe counting efficiency of the K-alpha probe design and variance-based statistical analysis with the three-sigma criteria

    International Nuclear Information System (INIS)

    Povoski, Stephen P; Chapman, Gregg J; Murrey, Douglas A; Lee, Robert; Martin, Edward W; Hall, Nathan C

    2013-01-01

    Intraoperative detection of 18 F-FDG-avid tissue sites during 18 F-FDG-directed surgery can be very challenging when utilizing gamma detection probes that rely on a fixed target-to-background (T/B) ratio (ratiometric threshold) for determination of probe positivity. The purpose of our study was to evaluate the counting efficiency and the success rate of in situ intraoperative detection of 18 F-FDG-avid tissue sites (using the three-sigma statistical threshold criteria method and the ratiometric threshold criteria method) for three different gamma detection probe systems. Of 58 patients undergoing 18 F-FDG-directed surgery for known or suspected malignancy using gamma detection probes, we identified nine 18 F-FDG-avid tissue sites (from amongst seven patients) that were seen on same-day preoperative diagnostic PET/CT imaging, and for which each 18 F-FDG-avid tissue site underwent attempted in situ intraoperative detection concurrently using three gamma detection probe systems (K-alpha probe, and two commercially-available PET-probe systems), and then were subsequently surgical excised. The mean relative probe counting efficiency ratio was 6.9 (± 4.4, range 2.2–15.4) for the K-alpha probe, as compared to 1.5 (± 0.3, range 1.0–2.1) and 1.0 (± 0, range 1.0–1.0), respectively, for two commercially-available PET-probe systems (P < 0.001). Successful in situ intraoperative detection of 18 F-FDG-avid tissue sites was more frequently accomplished with each of the three gamma detection probes tested by using the three-sigma statistical threshold criteria method than by using the ratiometric threshold criteria method, specifically with the three-sigma statistical threshold criteria method being significantly better than the ratiometric threshold criteria method for determining probe positivity for the K-alpha probe (P = 0.05). Our results suggest that the improved probe counting efficiency of the K-alpha probe design used in conjunction with the three

  16. Intraoperative detection of ¹⁸F-FDG-avid tissue sites using the increased probe counting efficiency of the K-alpha probe design and variance-based statistical analysis with the three-sigma criteria.

    Science.gov (United States)

    Povoski, Stephen P; Chapman, Gregg J; Murrey, Douglas A; Lee, Robert; Martin, Edward W; Hall, Nathan C

    2013-03-04

    Intraoperative detection of (18)F-FDG-avid tissue sites during 18F-FDG-directed surgery can be very challenging when utilizing gamma detection probes that rely on a fixed target-to-background (T/B) ratio (ratiometric threshold) for determination of probe positivity. The purpose of our study was to evaluate the counting efficiency and the success rate of in situ intraoperative detection of (18)F-FDG-avid tissue sites (using the three-sigma statistical threshold criteria method and the ratiometric threshold criteria method) for three different gamma detection probe systems. Of 58 patients undergoing (18)F-FDG-directed surgery for known or suspected malignancy using gamma detection probes, we identified nine (18)F-FDG-avid tissue sites (from amongst seven patients) that were seen on same-day preoperative diagnostic PET/CT imaging, and for which each (18)F-FDG-avid tissue site underwent attempted in situ intraoperative detection concurrently using three gamma detection probe systems (K-alpha probe, and two commercially-available PET-probe systems), and then were subsequently surgical excised. The mean relative probe counting efficiency ratio was 6.9 (± 4.4, range 2.2-15.4) for the K-alpha probe, as compared to 1.5 (± 0.3, range 1.0-2.1) and 1.0 (± 0, range 1.0-1.0), respectively, for two commercially-available PET-probe systems (P < 0.001). Successful in situ intraoperative detection of 18F-FDG-avid tissue sites was more frequently accomplished with each of the three gamma detection probes tested by using the three-sigma statistical threshold criteria method than by using the ratiometric threshold criteria method, specifically with the three-sigma statistical threshold criteria method being significantly better than the ratiometric threshold criteria method for determining probe positivity for the K-alpha probe (P = 0.05). Our results suggest that the improved probe counting efficiency of the K-alpha probe design used in conjunction with the three-sigma statistical

  17. Clinical use of antibodies

    International Nuclear Information System (INIS)

    Baum, R.P.; Hoer, Gustav; Cox, P.H.; Buraggi, G.L.

    1991-01-01

    Use of monoclonal antibodies as tumour specific carrier molecules for therapeutic agents or as in vivo diagnostic reagents when labelled with radionuclides or NMR signal enhancers is attracting more and more attention. The potential is enormous but the technical problems are also considerable requiring the concerted action of many different scientific disciplines. This volume is based upon a symposium organised in Frankfurt in 1990 under the auspices of the European Association of Nuclear Medicines' Specialist Task Groups on Cardiology and the Utility of Labelled Antibodies. It gives a multidisciplinary review of the state of the art and of problems to be solved as well as recording the not inconsiderable successes which have been booked to date. The book will be of value as a reference to both clinicians and research scientists. refs.; figs.; tabs

  18. Delta antibody radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Kselikova, M; Urbankova, J

    1985-11-15

    The principle and procedure are described of the radioimmunoassay of delta antibody (delta-Ab) using the ABBOTT ANTI-DELTA kit by Abbott Co. A description is given of the kit, the working procedure and the method of evaluation. The results are reported of the incidence of delta-Ab in sera of patients with viral hepatitis B, in haemophiliacs, carriers of the hepatitis B virus surface antigen (HBsAg) and blood donors. The presence was detected of delta-Ab in one HBsAg carrier. The necessity is emphasized of delta-Ab determinations in the blood of donors in view of the antibody transfer with blood and blood preparations.

  19. [Antibody therapy for Alzheimer's disease].

    Science.gov (United States)

    Tabira, Takeshi; Matsumoto, Shin-Ei; Jin, Haifeng

    2011-11-01

    In order to avoid Abeta-induced autoimmune encephalitis, several monoclonal and polyclonal antibodies are in clinical trials. These are bapineuzumab, solanezumab, ponezumab, gantenerumab, BAN2401, gammaguard and octagam. Since each antibody has a different antigen epitope of Abeta, anti-amyloid activities are different. It is unknown which antibody is effective for Alzheimer disease, and we must wait for the result of clinical trials. Some patients who developed tissue amyloid plaque immuno-reactive (TAPIR) antibody showed slower decline after AN-1792 vaccination. We developed TAPIR-like monoclonal antibody, which was found to react with Abeta oligomers preferentially.

  20. Diversity of the murine antibody response targeting influenza A(H1N1pdm09) hemagglutinin.

    Science.gov (United States)

    Wilson, Jason R; Tzeng, Wen-Pin; Spesock, April; Music, Nedzad; Guo, Zhu; Barrington, Robert; Stevens, James; Donis, Ruben O; Katz, Jacqueline M; York, Ian A

    2014-06-01

    We infected mice with the 2009 influenza A pandemic virus (H1N1pdm09), boosted with an inactivated vaccine, and cloned immunoglobulins (Igs) from HA-specific B cells. Based on the redundancy in germline gene utilization, we inferred that between 72-130 unique IgH VDJ and 35 different IgL VJ combinations comprised the anti-HA recall response. The IgH VH1 and IgL VK14 variable gene families were employed most frequently. A representative panel of antibodies were cloned and expressed to confirm reactivity with H1N1pdm09 HA. The majority of the recombinant antibodies were of high avidity and capable of inhibiting H1N1pdm09 hemagglutination. Three of these antibodies were subtype-specific cross-reactive, binding to the HA of A/South Carolina/1/1918(H1N1), and one further reacted with A/swine/Iowa/15/1930(H1N1). These results help to define the genetic diversity of the influenza anti-HA antibody repertoire profile induced following infection and vaccination, which may facilitate the development of influenza vaccines that are more protective and broadly neutralizing. Protection against influenza viruses is mediated mainly by antibodies, and in most cases this antibody response is narrow, only providing protection against closely related viruses. In spite of this limited range of protection, recent findings indicate that individuals immune to one influenza virus may contain antibodies (generally a minority of the overall response) that are more broadly reactive. These findings have raised the possibility that influenza vaccines could induce a more broadly protective response, reducing the need for frequent vaccine strain changes. However, interpretation of these observations is hampered by the lack of quantitative characterization of the antibody repertoire. In this study, we used single-cell cloning of influenza HA-specific B cells to assess the diversity and nature of the antibody response to influenza hemagglutinin in mice. Our findings help to put bounds on the

  1. Synthesis and Preclinical Evaluation of Radioiodinated Hypericin Dicarboxylic Acid as a Necrosis Avid Agent in Rat Models of Induced Hepatic, Muscular, and Myocardial Necroses.

    Science.gov (United States)

    Li, Jindian; Zhang, Jian; Yang, Shengwei; Jiang, Cuihua; Zhang, DongJian; Jin, Qiaomei; Wang, Qin; Wang, Cong; Ni, Yicheng; Yin, Zhiqi; Song, Shaoli

    2016-01-04

    Myocardial infarction (MI) leads to substantial morbidity and mortality around the world. Accurate assessment of myocardial viability is essential to assist therapies and improve patient outcomes. (131)I-hypericin dicarboxylic acid ((131)I-HDA) was synthesized and evaluated as a potential diagnostic agent for earlier assessment of myocardium viability compared to its preceding counterpart (131)I-hypericin ((131)I-Hyp) with strong hydrophobic property, long plasma half-life, and high uptake in mononuclear phagocyte system (MPS). Herein, HDA was synthesized and characterized, and self-aggregation constant Kα was analyzed by spectrophotometry. Plasma half-life was determined in healthy rats by γ-counting. (131)I-HDA and (131)I-Hyp were prepared with iodogen as oxidant. In vitro necrosis avidity of (131)I-HDA and (131)I-Hyp was evaluated in necrotic cells induced by hyperthermia. Biodistribution was determined in rat models of induced necrosis using γ-counting, autoradiography, and histopathology. Earlier imaging of necrotic myocardium to assess myocardial viability was performed in rat models of reperfused myocardium infarction using single photon emission computed tomography/computed tomography (SPECT/CT). As a result, the self-aggregation constant Kα of HDA was lower than that of Hyp (105602 vs 194644, p HDA displayed a shorter blood half-life compared with (131)I-Hyp (9.21 vs 31.20 h, p HDA relative to that with (131)I-Hyp (5.48 vs 4.63, p HDA showed a higher necrotic-viable myocardium ratio (7.32 vs 3.20, p HDA achieved imaging of necrotic myocardium at 6 h postinjection (p.i.) with SPECT/CT, earlier than what (131)I-Hyp did. Therefore, (131)I-HDA may serve as a promising necrosis-avid diagnostic agent for earlier imaging of necrotic myocardium compared with (131)I-Hyp. This may support further development of radiopharmaceuticals ((123)I and (99m)Tc) based on HDA for SPECT/CT of necrotic myocardium.

  2. PET/CT-guided percutaneous biopsy of FDG-avid metastatic bone lesions in patients with advanced lung cancer: a safe and effective technique

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Wei; Hao, Bing; Chen, Hao-jun; Zhao, Long; Luo, Zuo-ming; Wu, Hua; Sun, Long [The First Affiliated Hospital of Xiamen University, Department of Nuclear Medicine and Minnan PET Center, Xiamen Cancer Hospital, Xiamen (China)

    2017-01-15

    {sup 18}F-FDG PET/CT should be performed before a diagnostic biopsy site is chosen in patients with a high clinical suspicion of aggressive, advanced tumour. The aim of this study was to evaluate the safety and efficacy of {sup 18}F-FDG PET/CT in guiding biopsy of bone metastases in patients with advanced lung cancer. PET/CT-guided percutaneous core biopsies were performed in 51 consecutive patients with suspected lung cancer and {sup 18}F-FDG-avid bone lesions after whole-body {sup 18}F-FDG PET/CT scans. Generally, one tissue sample was obtained from each patient. The final diagnoses were established on the basis of the histology results. The histopathological and molecular testing results were systematically evaluated. A total of 53 samples were obtained for histological examination or molecular testing as a second biopsy was required in two patients in whom the pathological diagnosis was unclear following the first biopsy. The pathological diagnosis and lung cancer classification were confirmed in 48 patients. The epidermal growth factor receptor mutation status was determined in 23 biopsies, and the mutation rate was 30.4 % (7/23). The anaplastic lymphoma kinase mutation status was determined in 19 biopsies, and the mutation rate was 31.6 % (6/19). Two of the 51 biopsies were positive for non-Hodgkin's lymphoma and one was positive for metastatic renal cell carcinoma. The first-time diagnostic success rate of biopsy was 96.1 % (49/51) and the overall diagnostic success rate and sensitivity were 100 %. All 51 patients were eventually confirmed as having stage IV disease. No serious complications were encountered and the average biopsy time was 30 min. PET/CT-guided percutaneous biopsy of {sup 18}F-FDG-avid bone metastases is an effective and safe method that yields a high diagnostic success rate in the evaluation of hypermetabolic bone lesions in patients with suspected advanced lung cancer. (orig.)

  3. Use of JH4 joining segment gene by an anti-arsonate antibody that bears the major A-strain cross-reactive idiotype but displays diminished antigen binding.

    Science.gov (United States)

    Slaughter, C A; Jeske, D J; Kuziel, W A; Milner, E C; Capra, J D

    1984-06-01

    One of the antibody families utilized by the A/J mouse in its response to p-azophenylarsonate (Ars) is characterized by the expression of the major anti-arsonate cross-reactive idiotype (CRI) of the A strain. This family has been termed the Ars-A family. A hybridoma antibody (HP 101F11 ) obtained after immunization of an A/J mouse with Ars was identified initially as displaying the CRI, but was subsequently found to bind antigen at a level much lower than most members of the Ars-A family. The results of binding studies suggested that HP 101F11 possesses reduced avidity for antigen. When isolated light and heavy chains were allowed to recombine with the heavy and light chains of a strongly antigen-binding, strongly CRI-positive antibody of the Ars-A family (HP 93G7 ), the low level of antigen binding by HP 101F11 was found to be due to a structurally variant heavy chain. Whereas antibodies of the Ars-A family with normal avidity for antigen had been shown to use the JH2 joining segment gene, amino acid sequence analysis of HP 101F11 revealed that this antibody has a JH segment with a sequence identical to that encoded by a portion of a different JH gene, JH4 . The implication that 101F11 uses the JH4 gene instead of JH2 was supported by the observation that the productively rearranged gene is associated with an Eco R1 restriction fragment 0.95 Kb smaller than the corresponding fragments of Ars-A hybridomas with normal avidity for antigen. The size difference of 0.95 Kb corresponds exactly to the known distance between the JH2 and JH4 genes in BALB/c germline DNA. In addition to the structural differences immediately attributable to the use of JH4 , HP 101F11 has shown an amino acid interchange in the DH segment, and a single amino acid deletion at the DH-JH boundary. These results show that variation among members of the Ars-A family in the DH and/or JH segments provides alternative structural forms of Ars-A antibodies upon which selective processes can operate

  4. [Study of anti-idiotype antibodies to human monoclonal antibody].

    Science.gov (United States)

    Harada, R; Takahashi, N; Owaki, I; Kannagi, R; Endo, N; Morita, N; Inoue, M

    1992-02-01

    A human monoclonal antibody, ll-50 (IgM, lambda), was generated, which reacted specifically with a major of glycolipid present in LS174T colon cancer cells. The glycolipid antigen which reacted with the ll-50 antibody was expected to four sugar residues from its TLC mobility, and it was ascertained that the glycolipid antigen which reacted with ll-50 antibody might be Lc4 antigen [Gal beta 1----3 GLcNAc beta 1----3 Gal beta 1----4 Glc beta 1----1 Cer] judging from TLC immunostaining and ELISA when the reactivity of ll-50 antibody was tested using various pure glycolipids in 3-5 sugar residues as an antigen. Sera in patients with malignant disorders and healthy individuals were analyzed by Sandwich assay of immobilized and biotinylated ll-50 antibody. The serum of the Lc4 antigen recognized by ll-50 antibody was significantly higher in patients with malignant disorders than that in healthy individuals (p less than 0.05). Three mouse monoclonal anti-idiotype antibodies, G3, B3 and C5 (all IgG1), were generated by the immunization of BALB/c mice with ll-50 antibody. These anti-idiotype antibodies specifically bound to to human monoclonal antibody, ll-50 and had a significant inhibitory activity towards the binding of ll-50 antibody to the Lc4 antigen. This indicated that these anti-idiotype antibodies, G3, B3, and C5, were paratope-related anti-idiotype antibodies. G3, B3, and C5 were expected to define the nearest idiotope because they could mutually inhibit ll-50 antibody. Sera in patients with malignant disorders and healthy individuals were analyzed by Sandwich assay of immobilized and biotinylated anti-idiotype antibodies, G3, B3, and C5. As to the ll-50 like antibodies defined by C5 (Id-C5+), the mean serum level in patients with malignant disorders was significantly higher than that in healthy individuals (p less than 0.05). As to the ll-50 like antibodies defined by B3 (Id-B3+), the mean serum level in patients with malignant disorders was significantly higher

  5. Comparison of two threshold detection criteria methodologies for determination of probe positivity for intraoperative in situ identification of presumed abnormal 18F-FDG-avid tissue sites during radioguided oncologic surgery.

    Science.gov (United States)

    Chapman, Gregg J; Povoski, Stephen P; Hall, Nathan C; Murrey, Douglas A; Lee, Robert; Martin, Edward W

    2014-09-13

    Intraoperative in situ identification of (18)F-FDG-avid tissue sites during radioguided oncologic surgery remains a significant challenge for surgeons. The purpose of our study was to evaluate the 1.5-to-1 ratiometric threshold criteria method versus the three-sigma statistical threshold criteria method for determination of gamma detection probe positivity for intraoperative in situ identification of presumed abnormal (18)F-FDG-avid tissue sites in a manner that was independent of the specific type of gamma detection probe used. From among 52 patients undergoing appropriate in situ evaluation of presumed abnormal (18)F-FDG-avid tissue sites during (18)F-FDG-directed surgery using 6 available gamma detection probe systems, a total of 401 intraoperative gamma detection probe measurement sets of in situ counts per second measurements were cumulatively taken. For the 401 intraoperative gamma detection probe measurement sets, probe positivity was successfully met by the 1.5-to-1 ratiometric threshold criteria method in 150/401 instances (37.4%) and by the three-sigma statistical threshold criteria method in 259/401 instances (64.6%) (P < 0.001). Likewise, the three-sigma statistical threshold criteria method detected true positive results at target-to-background ratios much lower than the 1.5-to-1 target-to-background ratio of the 1.5-to-1 ratiometric threshold criteria method. The three-sigma statistical threshold criteria method was significantly better than the 1.5-to-1 ratiometric threshold criteria method for determination of gamma detection probe positivity for intraoperative in situ detection of presumed abnormal (18)F-FDG-avid tissue sites during radioguided oncologic surgery. This finding may be extremely important for reshaping the ongoing and future research and development of gamma detection probe systems that are necessary for optimizing the in situ detection of radioisotopes of higher-energy gamma photon emissions used during radioguided oncologic surgery.

  6. Hõimupäevad 2004

    Index Scriptorium Estoniae

    2004-01-01

    Näitusi: Tallinna Pedagoogikaülikooli Akadeemilises Raamatukogus Eesti Kunstiakadeemia ekspeditsiooninäitus "Seto' täämbä" 12. X-13. XI. Obinitsas kontor-galeriis "Hal'as kunn" Vladimir Nagovitsõni näitus "Põhja-Udmurdi jumalad" 12. X-1. XI. E. Vilde ja A. H. Tammsaare memoriaalmuuseumis Valt Ernshtreidi ja Zane Graudina fotonäitus "Inter/rational" 13. X-1. XI. Eesti Rahva Muuseumi Näitustemajas näitus "Pruudi-vara" (kuraator Svetlana Karm, kujundaja Jane Liiv)15. X-31. XII

  7. Evading the joint decision trap

    DEFF Research Database (Denmark)

    Stenbæk, Jørgen; Jensen, Mads Christian Dagnis

    2016-01-01

    spending level. In addition, the external environment with the fiscal and economic crisis created a momentum for reduced expenditures. Those against the reduction, the member states in favour of agriculture and cohesion, were not able to avoid cutbacks. Member states in favour of the cohesion policy faced...

  8. Microbials for the production of monoclonal antibodies and antibody fragments.

    Science.gov (United States)

    Spadiut, Oliver; Capone, Simona; Krainer, Florian; Glieder, Anton; Herwig, Christoph

    2014-01-01

    Monoclonal antibodies (mAbs) and antibody fragments represent the most important biopharmaceutical products today. Because full length antibodies are glycosylated, mammalian cells, which allow human-like N-glycosylation, are currently used for their production. However, mammalian cells have several drawbacks when it comes to bioprocessing and scale-up, resulting in long processing times and elevated costs. By contrast, antibody fragments, that are not glycosylated but still exhibit antigen binding properties, can be produced in microbial organisms, which are easy to manipulate and cultivate. In this review, we summarize recent advances in the expression systems, strain engineering, and production processes for the three main microbials used in antibody and antibody fragment production, namely Saccharomyces cerevisiae, Pichia pastoris, and Escherichia coli. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Potential role of combined FDG PET/CT & contrast enhancement MRI in a rectal carcinoma model with nodal metastases characterized by a poor FDG-avidity.

    Science.gov (United States)

    Farace, Paolo; Conti, Giamaica; Merigo, Flavia; Tambalo, Stefano; Marzola, Pasquina; Sbarbati, Andrea; Quarta, Carmelo; D'Ambrosio, Daniela; Chondrogiannis, Sotirios; Nanni, Cristina; Rubello, Domenico

    2012-04-01

    To investigate the additional role of MRI contrast enhancement (CE) in the primary tumor and the FDG uptake at PET in the lymph-node metastases. A model of colorectal cancer induced by orthotopic HT-29 cells microinjection, producing pelvic lymph node metastases, was assessed using CE-MRI and FDG-PET. Histology and GLUT-1 immunohistochemistry were performed on primary tumors and iliac lymph nodes. Primary tumors were characterized by low FDG-uptake but high CE-MRI, particularly at tumor periphery. Undetectable FDG-uptake characterized the metastatic lymph-nodes. Histology revealed large stromal bundles at tumor periphery and a dense network of stromal fibers and neoplastic cells in the inner portion of the tumors. Both primary tumors and positive lymph nodes showed poor GLUT-1 staining. Our data support the complementary role of MRI-CE and FDG PET in some types of carcinomas characterized by abundant cancer-associated stroma and poor FDG avidity consequent to poor GLUT-1 transported. In these tumors FDG-PET alone may be not completely adequate to obtain an adequate tumor radiotherapy planning, and a combination with dual CE-MRI is strongly recommended. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. Potential role of combined FDG PET/CT and contrast enhancement MRI in a rectal carcinoma model with nodal metastases characterized by a poor FDG-avidity

    International Nuclear Information System (INIS)

    Farace, Paolo; Conti, Giamaica; Merigo, Flavia; Tambalo, Stefano; Marzola, Pasquina; Sbarbati, Andrea; Quarta, Carmelo; D’Ambrosio, Daniela; Chondrogiannis, Sotirios; Nanni, Cristina; Rubello, Domenico

    2012-01-01

    Purpose: To investigate the additional role of MRI contrast enhancement (CE) in the primary tumor and the FDG uptake at PET in the lymph-node metastases. Materials and methods: A model of colorectal cancer induced by orthotopic HT-29 cells microinjection, producing pelvic lymph node metastases, was assessed using CE-MRI and FDG-PET. Histology and GLUT-1 immunohistochemistry were performed on primary tumors and iliac lymph nodes. Results: Primary tumors were characterized by low FDG-uptake but high CE-MRI, particularly at tumor periphery. Undetectable FDG-uptake characterized the metastatic lymph-nodes. Histology revealed large stromal bundles at tumor periphery and a dense network of stromal fibers and neoplastic cells in the inner portion of the tumors. Both primary tumors and positive lymph nodes showed poor GLUT-1 staining. Conclusion: Our data support the complementary role of MRI-CE and FDG PET in some types of carcinomas characterized by abundant cancer-associated stroma and poor FDG avidity consequent to poor GLUT-1 transported. In these tumors FDG-PET alone may be not completely adequate to obtain an adequate tumor radiotherapy planning, and a combination with dual CE-MRI is strongly recommended.

  11. Radioimmunoassay with heterologous antibody (hetero-antibody RIA)

    International Nuclear Information System (INIS)

    Iwasawa, Atsushi; Hayashi, Hiroaki; Itoh, Zen; Wakabayashi, Katsumi

    1991-01-01

    To develop a homologous radioimmunoassay (RIA) for a hormone of a small or rare animal often meets difficulty in collecting a large amount of purified antigen required for antibody production. On the other hand, to employ a heterologous RIA to estimate the hormone often gives poor sensitivity. To overcome this difficulty, a 'hetero-antibody' RIA was studied. In a hetero-antibody RIA system, a purified preparation of a hormone is used for radioiodination and standardization and a heterologous antibody to the hormone is used for the first antibody. Canine motilin and rat LH were selected as examples, and anti-porcine motilin and anti-hCG, anti-hCGβ or anti-ovine LHβ was used as the heterologous antibody. The sensitivities of the hetero-antibody RIAs were much higher than those of heterologous RIAs in any case, showing that these hetero-antibody RIA systems were suitable for practical use. To clarify the principle of hetero-antibody RIA, antiserum to porcine motilin was fractionated on an affinity column where canine motilin was immobilized. The fraction bound had greater constants of affinity with both porcine and canine motilins than the rest of the antibody fractions. This fraction also reacted with a synthetic peptide corresponding to the C-terminal sequence common to porcine and canine motilins in a competitive binding test with labeled canine motilin. These results suggest that an antibody population having high affinity and cross-reactivity is present in polyclonal antiserum and indicate that the population can be used in hetero-antibody RIA at an appropriate concentration. (author)

  12. Use of an in vivo FTA assay to assess the magnitude, functional avidity and epitope variant cross-reactivity of T cell responses following HIV-1 recombinant poxvirus vaccination.

    Directory of Open Access Journals (Sweden)

    Danushka K Wijesundara

    Full Text Available Qualitative characteristics of cytotoxic CD8+ T cells (CTLs are important in measuring the effectiveness of CTLs in controlling HIV-1 infections. Indeed, in recent studies patients who are naturally resistant to HIV-1 infections have been shown to possess CTLs that are of high functional avidity and have a high capacity to recognize HIV epitope variants, when compared to HIV-1 infection progressors. When developing efficacious vaccines, assays that can effectively measure CTL quality specifically in vivo are becoming increasingly important. Here we report the use of a recently developed high-throughput multi-parameter technique, known as the fluorescent target array (FTA assay, to simultaneously measure CTL killing magnitude, functional avidity and epitope variant cross-reactivity in real time in vivo. In the current study we have applied the FTA assay as a screening tool to assess a large cohort of over 20 different HIV-1 poxvirus vaccination strategies in mice. This screen revealed that heterologous poxvirus prime-boost vaccination regimes (i.e., recombinant fowlpox (FPV-HIV prime followed by a recombinant vaccinia virus (VV-HIV booster were the most effective in generating high quality CTL responses in vivo. In conclusion, we have demonstrated how the FTA assay can be utilized as a cost effective screening tool (by reducing the required number of animals by >100 fold, to evaluate a large range of HIV-1 vaccination strategies in terms of CTL avidity and variant cross-reactivity in an in vivo setting.

  13. Use of an in vivo FTA assay to assess the magnitude, functional avidity and epitope variant cross-reactivity of T cell responses following HIV-1 recombinant poxvirus vaccination.

    Science.gov (United States)

    Wijesundara, Danushka K; Ranasinghe, Charani; Jackson, Ronald J; Lidbury, Brett A; Parish, Christopher R; Quah, Benjamin J C

    2014-01-01

    Qualitative characteristics of cytotoxic CD8+ T cells (CTLs) are important in measuring the effectiveness of CTLs in controlling HIV-1 infections. Indeed, in recent studies patients who are naturally resistant to HIV-1 infections have been shown to possess CTLs that are of high functional avidity and have a high capacity to recognize HIV epitope variants, when compared to HIV-1 infection progressors. When developing efficacious vaccines, assays that can effectively measure CTL quality specifically in vivo are becoming increasingly important. Here we report the use of a recently developed high-throughput multi-parameter technique, known as the fluorescent target array (FTA) assay, to simultaneously measure CTL killing magnitude, functional avidity and epitope variant cross-reactivity in real time in vivo. In the current study we have applied the FTA assay as a screening tool to assess a large cohort of over 20 different HIV-1 poxvirus vaccination strategies in mice. This screen revealed that heterologous poxvirus prime-boost vaccination regimes (i.e., recombinant fowlpox (FPV)-HIV prime followed by a recombinant vaccinia virus (VV)-HIV booster) were the most effective in generating high quality CTL responses in vivo. In conclusion, we have demonstrated how the FTA assay can be utilized as a cost effective screening tool (by reducing the required number of animals by >100 fold), to evaluate a large range of HIV-1 vaccination strategies in terms of CTL avidity and variant cross-reactivity in an in vivo setting.

  14. Bivalent Llama Single-Domain Antibody Fragments against Tumor Necrosis Factor Have Picomolar Potencies due to Intramolecular Interactions

    Directory of Open Access Journals (Sweden)

    Els Beirnaert

    2017-07-01

    Full Text Available The activity of tumor necrosis factor (TNF, a cytokine involved in inflammatory pathologies, can be inhibited by antibodies or trap molecules. Herein, llama-derived variable heavy-chain domains of heavy-chain antibody (VHH, also called Nanobodies™ were generated for the engineering of bivalent constructs, which antagonize the binding of TNF to its receptors with picomolar potencies. Three monomeric VHHs (VHH#1, VHH#2, and VHH#3 were characterized in detail and found to bind TNF with sub-nanomolar affinities. The crystal structures of the TNF–VHH complexes demonstrate that VHH#1 and VHH#2 share the same epitope, at the center of the interaction area of TNF with its TNFRs, while VHH#3 binds to a different, but partially overlapping epitope. These structures rationalize our results obtained with bivalent constructs in which two VHHs were coupled via linkers of different lengths. Contrary to conventional antibodies, these bivalent Nanobody™ constructs can bind to a single trimeric TNF, thus binding with avidity and blocking two of the three receptor binding sites in the cytokine. The different mode of binding to antigen and the engineering into bivalent constructs supports the design of highly potent VHH-based therapeutic entities.

  15. Human antibody technology and the development of antibodies against cytomegalovirus.

    Science.gov (United States)

    Ohlin, Mats; Söderberg-Nauclér, Cecilia

    2015-10-01

    Cytomegalovirus (CMV) is a virus that causes chronic infections in a large set of the population. It may cause severe disease in immunocompromised individuals, is linked to immunosenescence and implied to play an important role in the pathogenesis of cardiovascular diseases and cancer. Modulation of the immune system's abilities to manage the virus represent a highly viable therapeutic option and passive immunotherapy with polyclonal antibody preparations is already in clinical use. Defined monoclonal antibodies offer many advantages over polyclonal antibodies purified from serum. Human CMV-specific monoclonal antibodies have consequently been thoroughly investigated with respect to their potential in the treatment of diseases caused by CMV. Recent advances in human antibody technology have substantially expanded the breadth of antibodies for such applications. This review summarizes the fundamental basis for treating CMV disease by use of antibodies, the basic technologies to be used to develop such antibodies, and relevant human antibody specificities available to target this virus. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Tabhu: tools for antibody humanization

    DEFF Research Database (Denmark)

    Olimpieri, Pier Paolo; Marcatili, Paolo; Tramontano, Anna

    2015-01-01

    Antibodies are rapidly becoming essential tools in the clinical practice, given their ability to recognize their cognate antigens with high specificity and affinity, and a high yield at reasonable costs in model animals. Unfortunately, when administered to human patients, xenogeneic antibodies can...... elicit unwanted and dangerous immunogenic responses. Antibody humanization methods are designed to produce molecules with a better safety profile still maintaining their ability to bind the antigen. This can be accomplished by grafting the non-human regions determining the antigen specificity...... and time-consuming experiments. Here we present tools for antibody humanization (Tabhu) a web server for antibody humanization. Tabhu includes tools for human template selection, grafting, back-mutation evaluation, antibody modelling and structural analysis, helping the user in all the critical steps...

  17. Cancer imaging with radiolabeled antibodies

    International Nuclear Information System (INIS)

    Goldenberg, D.M.

    1990-01-01

    This book presents a perspective of the use of antibodies to target diagnostic isotopes to tumors. Antibodies with reasonable specificity can be developed against almost any substance. If selective targeting to cancer cells can be achieved, the prospects for a selective therapy are equally intriguing. But the development of cancer detection, or imaging, with radiolabeled antibodies has depended upon advances in a number of different areas, including cancer immunology and immunochemistry for identifying suitable antigen targets and antibodies to these targets, tumor biology for model systems, radiochemistry for he attachment of radionuclides to antibodies, molecular biology for reengineering the antibodies for safer and more effective use in humans, and nuclear medicine for providing the best imaging protocols and instrumentation to detect minute amounts of elevated radioactivity against a background of considerable noise. Accordingly, this book has been organized to address the advances that are being made in many of these areas

  18. Genetically engineered multivalent single chain antibody constructs for cancer therapy

    International Nuclear Information System (INIS)

    Surinder Batra

    2006-01-01

    increase its tumor: normal tissue ratio for improved therapeutic index, we engineered a variety antibody constructs. These constructs were evaluated using novel approaches like special radionuclides, pretargeting and optimization. Due to the smaller size, the engineered antibody molecules should penetrate better throughout a tumor mass, with less dose heterogeneity, than is the case with intact IgG. Multivalent scFvs with an appropriate radionuclide, therefore, hold promising prospects for cancer therapy and clinical imaging in MAb-based radiopharmaceuticals. In addition, the human anti-mouse antibodies (HAMA) responses in patients against antibody-based therapy are usually directed against the immunoglobulin constant regions; however, anti-idiotypic responses can also be detected. The HAMA responses reduce the efficacy of treatment by removing the circulating antibody molecules, fragments, and possibly scFvs by altering the pharmacokinetic properties of the antibody. HAMA responses against divalent IgG, divalent Ig fragments, and possibly multimeric scFvs could cause immune complex formation with hypersensitivity or allergic reactions that could be harmful to patients. The use of small molecules, such as scFvs (monomeric as well as multimeric), with their shorter biological half-lives and the lack of the constant regions and humanized variable (binding regions) performed in our studies should reduce the development of HAMA. The generation of humanized and fully human scFvs should further reduce the development of HAMA. Specific accomplishments on the project are the production of large amounts of recombinant antibodies as they are required in large amounts for cancer diagnosis and therapy. A variety of single-chain Fv (scFv) constructs were engineered for the desired pharmacokinetic properties. Tetrameric and dimeric scFvs showed a two-fold advantage: (1) there was a considerable gain in avidity as compared to smaller fragments, and (2) the biological half-life was more

  19. Monoclonal antibodies for treating cancer

    International Nuclear Information System (INIS)

    Dillman, R.O.

    1989-01-01

    The purpose of this study is to assess the current status of in-vivo use of monoclonal antibodies for treating cancer. Publications appearing between 1980 and 1988 were identified by computer searches using MEDLINE and CANCERLIT, by reviewing the table of contents of recently published journals, and by searching bibliographies of identified books and articles. More than 700 articles, including peer-reviewed articles and book chapters, were identified and selected for analysis. The literature was reviewed and 235 articles were selected as relevant and representative of the current issues and future applications for in-vivo monoclonal antibodies for cancer therapy and of the toxicity and efficacy which has been associated with clinical trials. Approaches include using antibody alone (interacting with complement or effector cells or binding directly with certain cell receptors) and immunoconjugates (antibody coupled to radioisotopes, drugs, toxins, or other biologicals). Most experience has been with murine antibodies. Trials of antibody alone and radiolabeled antibodies have confirmed the feasibility of this approach and the in-vivo trafficking of antibodies to tumor cells. However, tumor cell heterogeneity, lack of cytotoxicity, and the development of human antimouse antibodies have limited clinical efficacy. Although the immunoconjugates are very promising, heterogeneity and the antimouse immune response have hampered this approach as has the additional challenge of chemically or genetically coupling antibody to cytotoxic agents. As a therapeutic modality, monoclonal antibodies are still promising but their general use will be delayed for several years. New approaches using human antibodies and reducing the human antiglobulin response should facilitate treatment. 235 references

  20. Tumor imaging with monoclonal antibodies

    International Nuclear Information System (INIS)

    Haisma, H.; Hilgers, J.

    1987-01-01

    Many monoclonal antibodies directed against tumor-associated antigens have been identified, but so far none of these are tumor specific. Polyclonal and monoclonal antibodies have been used for imaging of a wide variety of tumors with success. Radiolabeling of antibody is usually done with iodine isotopes of which 123 I is the best candidate for radioimmunodetection purposes. The labeling of antibodies through chelates makes it possible to use metal radioisotopes like 111 In, which is the best radioisotope for imaging with monoclonal antibodies due to its favorable half-life of 2.5 days. Usually imaging cannot be performed within 24 h after injection, but clearance of antibody can be increased by using F(ab) 2 of Fab. Another approach is to clear non-bound antibody by a second antibody, directed against the first. The detection limit of immunoimaging is about 2 cm, but will be improved by tomography or SPECT. There is still a high false positive and false negative rate, which makes it impossible to use radioimmunodetection as the only technique for diagnosis of tumors. In combination with other detection techniques, tumor imaging with monoclonal antibodies can improve diagnosis. 44 refs.; 3 tabs

  1. Burkholderia pseudomallei Evades Nramp1 (Slc11a1- and NADPH Oxidase-Mediated Killing in Macrophages and Exhibits Nramp1-Dependent Virulence Gene Expression

    Directory of Open Access Journals (Sweden)

    Veerachat Muangsombut

    2017-08-01

    Full Text Available Bacterial survival in macrophages can be affected by the natural resistance-associated macrophage protein 1 (Nramp1; also known as solute carrier family 11 member a1 or Slc11a1 which localizes to phagosome membranes and transports divalent cations, including iron. Little is known about the role of Nramp1 in Burkholderia infection, in particular whether this differs for pathogenic species like Burkholderia pseudomallei causing melioidosis or non-pathogenic species like Burkholderia thailandensis. Here we show that transfected macrophages stably expressing wild-type Nramp1 (Nramp1+ control the net replication of B. thailandensis, but not B. pseudomallei. Control of B. thailandensis was associated with increased cytokine responses, and could be abrogated by blocking NADPH oxidase-mediated production of reactive oxygen species but not by blocking generation of reactive nitrogen species. The inability of Nramp1+ macrophages to control B. pseudomallei was associated with rapid escape of bacteria from phagosomes, as indicated by decreased co-localization with LAMP1 compared to B. thailandensis. A B. pseudomallei bipB mutant impaired in escape from phagosomes was controlled to a greater extent than the parent strain in Nramp1+ macrophages, but was also attenuated in Nramp1− cells. Consistent with reduced escape from phagosomes, B. thailandensis formed fewer multinucleated giant cells in Nramp1+ macrophages at later time points compared to B. pseudomallei. B. pseudomallei exhibited elevated transcription of virulence-associated genes of Type VI Secretion System cluster 1 (T6SS-1, the Bsa Type III Secretion System (T3SS-3 and the bimA gene required for actin-based motility in Nramp1+ macrophages. Nramp1+ macrophages were found to contain decreased iron levels that may impact on expression of such genes. Our data show that B. pseudomallei is able to evade Nramp1- and NADPH oxidase-mediated killing in macrophages and that expression of virulence

  2. Trypanosoma cruzi Evades the Complement System as an Efficient Strategy to Survive in the Mammalian Host: The Specific Roles of Host/Parasite Molecules and Trypanosoma cruzi Calreticulin

    Directory of Open Access Journals (Sweden)

    Galia Ramírez-Toloza

    2017-09-01

    Full Text Available American Trypanosomiasis is an important neglected reemerging tropical parasitism, infecting about 8 million people worldwide. Its agent, Trypanosoma cruzi, exhibits multiple mechanisms to evade the host immune response and infect host cells. An important immune evasion strategy of T. cruzi infective stages is its capacity to inhibit the complement system activation on the parasite surface, avoiding opsonizing, immune stimulating and lytic effects. Epimastigotes, the non-infective form of the parasite, present in triatomine arthropod vectors, are highly susceptible to complement-mediated lysis while trypomastigotes, the infective form, present in host bloodstream, are resistant. Thus T. cruzi susceptibility to complement varies depending on the parasite stage (amastigote, trypomastigotes or epimastigote and on the T. cruzi strain. To avoid complement-mediated lysis, T. cruzi trypomastigotes express on the parasite surface a variety of complement regulatory proteins, such as glycoprotein 58/68 (gp58/68, T. cruzi complement regulatory protein (TcCRP, trypomastigote decay-accelerating factor (T-DAF, C2 receptor inhibitor trispanning (CRIT and T. cruzi calreticulin (TcCRT. Alternatively, or concomitantly, the parasite captures components with complement regulatory activity from the host bloodstream, such as factor H (FH and plasma membrane-derived vesicles (PMVs. All these proteins inhibit different steps of the classical (CP, alternative (AP or lectin pathways (LP. Thus, TcCRP inhibits the CP C3 convertase assembling, gp58/68 inhibits the AP C3 convertase, T-DAF interferes with the CP and AP convertases assembling, TcCRT inhibits the CP and LP, CRIT confers ability to resist the CP and LP, FH is used by trypomastigotes to inhibit the AP convertases and PMVs inhibit the CP and LP C3 convertases. Many of these proteins have similar molecular inhibitory mechanisms. Our laboratory has contributed to elucidate the role of TcCRT in the host

  3. Estimating the probability of polyreactive antibodies 4E10 and 2F5 disabling a gp41 trimer after T cell-HIV adhesion.

    Directory of Open Access Journals (Sweden)

    Bin Hu

    2014-01-01

    Full Text Available A few broadly neutralizing antibodies, isolated from HIV-1 infected individuals, recognize epitopes in the membrane proximal external region (MPER of gp41 that are transiently exposed during viral entry. The best characterized, 4E10 and 2F5, are polyreactive, binding to the viral membrane and their epitopes in the MPER. We present a model to calculate, for any antibody concentration, the probability that during the pre-hairpin intermediate, the transient period when the epitopes are first exposed, a bound antibody will disable a trivalent gp41 before fusion is complete. When 4E10 or 2F5 bind to the MPER, a conformational change is induced that results in a stably bound complex. The model predicts that for these antibodies to be effective at neutralization, the time to disable an epitope must be shorter than the time the antibody remains bound in this conformation, about five minutes or less for 4E10 and 2F5. We investigate the role of avidity in neutralization and show that 2F5 IgG, but not 4E10, is much more effective at neutralization than its Fab fragment. We attribute this to 2F5 interacting more stably than 4E10 with the viral membrane. We use the model to elucidate the parameters that determine the ability of these antibodies to disable epitopes and propose an extension of the model to analyze neutralization data. The extended model predicts the dependencies of IC50 for neutralization on the rate constants that characterize antibody binding, the rate of fusion of gp41, and the number of gp41 bridging the virus and target cell at the start of the pre-hairpin intermediate. Analysis of neutralization experiments indicate that only a small number of gp41 bridges must be disabled to prevent fusion. However, the model cannot determine the exact number from neutralization experiments alone.

  4. An Immunoglobulin G1 Monoclonal Antibody Highly Specific to the Wall of Cryptosporidium Oocysts

    Science.gov (United States)

    Weir, C.; Vesey, G.; Slade, M.; Ferrari, B.; Veal, D. A.; Williams, K.

    2000-01-01

    The detection of Cryptosporidium oocysts in drinking water is critically dependent on the quality of immunofluorescent reagents. Experiments were performed to develop a method for producing highly specific antibodies to Cryptosporidium oocysts that can be used for water testing. BALB/c mice were immunized with six different antigen preparations and monitored for immunoglobulin G (IgG) and IgM responses to the surface of Cryptosporidium oocysts. One group of mice received purified oocyst walls, a second group received a soluble protein preparation extracted from the outside of the oocyst wall, and the third group received whole inactivated oocysts. Three additional groups were immunized with sequentially prepared oocyst extracts to provide for a comparison of the immune response. Mice injected with the soluble protein extract demonstrated an IgG response to oocysts surface that was not seen in the whole-oocyst group. Mice injected with whole oocysts showed an IgM response only, while mice injected with purified oocyst walls showed little increase in IgM or IgG levels. Of the additional reported preparations only one, BME (2-mercaptoethanol treated), produced a weak IgM response to the oocyst wall. A mouse from the soluble oocyst extract group yielding a high IgG response was utilized to produce a highly specific IgG1 monoclonal antibody (Cry104) specific to the oocyst surface. Comparative flow cytometric analysis indicated that Cry104 has a higher avidity and specificity to oocysts in water concentrates than other commercially available antibodies. PMID:10973448

  5. Gu-4 suppresses affinity and avidity modulation of CD11b and improves the outcome of mice with endotoxemia and sepsis.

    Directory of Open Access Journals (Sweden)

    TingTing Yan

    Full Text Available BACKGROUND: Systemic leukocyte activation and disseminated leukocyte adhesion will impair the microcirculation and cause severe decrements in tissue perfusion and organ function in the process of severe sepsis. Gu-4, a lactosyl derivative, could selectively target CD11b to exert therapeutic effect in a rat model of severe burn shock. Here, we addressed whether Gu-4 could render protective effects on septic animals. METHODOLOGY/PRINCIPAL FINDINGS: On a murine model of endotoxemia induced by lipopolysaccharide (LPS, we found that the median effective dose (ED50 of Gu-4 was 0.929 mg/kg. In vivo treatment of Gu-4 after LPS challenge prominently attenuated LPS-induced lung injury and decreased lactic acid level in lung tissue. Using the ED50 of Gu-4, we also demonstrated that Gu-4 treatment significantly improved the survival rate of animals underwent sepsis induced by cecal ligation and puncture. By adhesion and transwell migration assays, we found that Gu-4 treatment inhibited the adhesion and transendothelial migration of LPS-stimulated THP-1 cells. By flow cytometry and microscopy, we demonstrated that Gu-4 treatment inhibited the exposure of active I-domain and the cluster formation of CD11b on the LPS-stimulated polymorphonuclear leukocytes. Western blot analyses further revealed that Gu-4 treatment markedly inhibited the activation of spleen tyrosine kinase in LPS-stimulated THP-1 cells. CONCLUSIONS/SIGNIFICANCE: Gu-4 improves the survival of mice underwent endotoxemia and sepsis, our in vitro investigations indicate that the possible underlying mechanism might involve the modulations of the affinity and avidity of CD11b on the leukocyte. Our findings shed light on the potential use of Gu-4, an interacting compound to CD11b, in the treatment of sepsis and septic shock.

  6. Diverse Epitope Specificity, Immunodominance Hierarchy, and Functional Avidity of Effector CD4 T Cells Established During Priming Is Maintained in Lung After Influenza A Virus Infection.

    Science.gov (United States)

    Richards, Katherine A; DiPiazza, Anthony T; Rattan, Ajitanuj; Knowlden, Zackery A G; Yang, Hongmei; Sant, Andrea J

    2018-01-01

    One of the major contributions to protective immunity to influenza viruses that is provided by virus-specific CD4 T cells is delivery of effector function to the infected lung. However, there is little known about the selection and breadth of viral epitope-specific CD4 T cells that home to the lung after their initial priming. In this study, using a mouse model of influenza A infection and an unbiased method of epitope identification, the viral epitope-specific CD4 T cells elicited after infection were identified and quantified. We found that a very diverse specificity of CD4 T cells is primed by infection, including epitopes from hemagglutinin, neuraminidase, matrix protein, nucleoprotein, and non-structural protein-1. Using peptide-specific cytokine EliSpots, the diversity and immunodominance hierarchies established in the lung-draining lymph node were compared with specificities of CD4 T cells that home to the lung. Our studies revealed that CD4 T cells of all epitope specificities identified in peripheral lymphoid tissue home back to the lung and that most of these lung-homing cells are localized within the tissue rather than the pulmonary vasculature. There is a striking shift of CD4 T cell functionality that enriches for IFN-γ production as cells are primed in the lymph node, enter the lung vasculature, and finally establish residency in the tissue, but with no apparent shifts in their functional avidity. We conclude that CD4 T cells of broad viral epitope specificity are recruited into the lung after influenza infection, where they then have the opportunity to encounter infected or antigen-bearing antigen-presenting cells.

  7. Red Blood Cell Antibody Identification

    Science.gov (United States)

    ... antibodies may or may not be associated with adverse reactions, and identification of the specific type of RBC ... the only things that can cause a transfusion reaction. The recipient's immune ... or to drugs that the donor may have taken. Rarely, antibodies in the plasma ...

  8. Structural Characterization of Peptide Antibodies

    DEFF Research Database (Denmark)

    Chailyan, Anna; Marcatili, Paolo

    2015-01-01

    The role of proteins as very effective immunogens for the generation of antibodies is indisputable. Nevertheless, cases in which protein usage for antibody production is not feasible or convenient compelled the creation of a powerful alternative consisting of synthetic peptides. Synthetic peptides...... can be modified to obtain desired properties or conformation, tagged for purification, isotopically labeled for protein quantitation or conjugated to immunogens for antibody production. The antibodies that bind to these peptides represent an invaluable tool for biological research and discovery....... To better understand the underlying mechanisms of antibody-antigen interaction here we present a pipeline developed by us to structurally classify immunoglobulin antigen binding sites and to infer key sequence residues and other variables that have a prominent role in each structural class....

  9. Radiolabeled antibodies in cancer. Oncology Overview

    International Nuclear Information System (INIS)

    1984-11-01

    Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories through the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Radiolabeled antibodies--labeling and imaging techniques; Radiolabeled antibodies--carcinoembryonic antigen; Radiolabeled antibodies--alpha-fetoprotein; Radiolabeled antibodies--human chorionic gonadotropin; Radiolabeled antibodies--ferritin; Radiolabeled antibodies--imaging of colorectal tumors; Radiolabeled antibodies--imaging of malignant melanoma; Radiolabeled antibodies--imaging of urogenital tumors; Radiolabeled antibodies--imaging of thyroid tumors; Radiolabeled antibodies--other clinical studies; Radiolabeled antibodies--selected preclinical studies; Radiolabeled antibodies--reviews

  10. New perspectives on recombinant human antibodies

    NARCIS (Netherlands)

    J. de Kruif (John); A.-R. van der Vuurst de Vries (Anne); L. Cilenti (L.); E. Boel (E.); W. van Ewijk (Willem); T. Logtenberg (Ton)

    1996-01-01

    textabstractThe limited potential of murine monoclonal antibodies for human immunotherapy has driven recent progress in recombinant antibody technology. Here, de Kruif and colleagues report on advances in the development and use of phage-antibody-display libraries.

  11. Measurement of antibodies to tubulin by radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Mead, G M; Cowin, P; Whitehouse, J M.A. [CRC Medical Oncology Unit, Southampton General Hospital, Southampton, U.K.

    1979-07-24

    A solid-phase double antibody radioimmunoassay capable of measuring antibody to tubulin, the principal component of microtubules, is described. This assay is simple, combining sensitivity with specificity and also allowing determination of antibody subclasses.

  12. Repeated Vaccination of Cows with HIV Env gp140 during Subsequent Pregnancies Elicits and Sustains an Enduring Strong Env-Binding and Neutralising Antibody Response.

    Directory of Open Access Journals (Sweden)

    Behnaz Heydarchi

    Full Text Available An important feature of a potential vaccine against HIV is the production of broadly neutralising antibodies (BrNAbs capable of potentially blocking infectivity of a diverse array of HIV strains. BrNAbs naturally arise in some HIV infected individuals after several years of infection and their serum IgG can neutralise various HIV strains across different subtypes. We previously showed that vaccination of cows with HIV gp140 AD8 trimers resulted in a high titre of serum IgG against HIV envelope (Env that had strong BrNAb activity. These polyclonal BrNAbs concentrated into the colostrum during the late stage of pregnancy and can be harvested in vast quantities immediately after calving. In this study, we investigated the effect of prolonged HIV gp140 vaccination on bovine colostrum IgG HIV Env-binding and BrNAb activity over subsequent pregnancies. Repeated immunisation led to a maintained high titre of HIV Env specific IgG in the colostrum batches, but this did not increase through repeated cycles. Colostrum IgG from all batches also strongly competed with sCD4 binding to gp140 Env trimer and with human-derived monoclonal VRC01 and b12 BrNAbs that bind the CD4 binding site (CD4bs. Furthermore, competition neutralisation assays using RSC3 Env gp120 protein core and a derivative CD4bs mutant, RSC3 Δ371I/P363N, showed that CD4bs neutralising antibodies contribute to the neutralising activity of all batches of purified bovine colostrum IgG. This result indicates that the high IgG titre/avidity of anti-CD4bs antibodies with BrNAb activity was achieved during the first year of vaccination and was sustained throughout the years of repeated vaccinations in the cow tested. Although IgG of subsequent colostrum batches may have a higher avidity towards the CD4bs, the overall breadth in neutralisation was not enhanced. This implies that the boosting vaccinations over 4 years elicited a polyclonal antibody response that maintained the proportion of both

  13. Structure of Simian Immunodeficiency Virus Envelope Spikes Bound with CD4 and Monoclonal Antibody 36D5.

    Science.gov (United States)

    Hu, Guiqing; Liu, Jun; Roux, Kenneth H; Taylor, Kenneth A

    2017-08-15

    The human immunodeficiency virus type 1 (HIV-1)/simian immunodeficiency virus (SIV) envelope spike (Env) mediates viral entry into host cells. The V3 loop of the gp120 component of the Env trimer contributes to the coreceptor binding site and is a target for neutralizing antibodies. We used cryo-electron tomography to visualize the binding of CD4 and the V3 loop monoclonal antibody (MAb) 36D5 to gp120 of the SIV Env trimer. Our results show that 36D5 binds gp120 at the base of the V3 loop and suggest that the antibody exerts its neutralization effect by blocking the coreceptor binding site. The antibody does this without altering the dynamics of the spike motion between closed and open states when CD4 is bound. The interaction between 36D5 and SIV gp120 is similar to the interaction between some broadly neutralizing anti-V3 loop antibodies and HIV-1 gp120. Two conformations of gp120 bound with CD4 are revealed, suggesting an intrinsic dynamic nature of the liganded Env trimer. CD4 binding substantially increases the binding of 36D5 to gp120 in the intact Env trimer, consistent with CD4-induced changes in the conformation of gp120 and the antibody binding site. Binding by MAb 36D5 does not substantially alter the proportions of the two CD4-bound conformations. The position of MAb 36D5 at the V3 base changes little between conformations, indicating that the V3 base serves as a pivot point during the transition between these two states. IMPORTANCE Glycoprotein spikes on the surfaces of SIV and HIV are the sole targets available to the immune system for antibody neutralization. Spikes evade the immune system by a combination of a thick layer of polysaccharide on the surface (the glycan shield) and movement between spike domains that masks the epitope conformation. Using SIV virions whose spikes were "decorated" with the primary cellular receptor (CD4) and an antibody (36D5) at part of the coreceptor binding site, we visualized multiple conformations trapped by the

  14. Dissecting Immunogenicity of Monoclonal Antibodies

    National Research Council Canada - National Science Library

    Snyder, Christopher

    2003-01-01

    The potential of monoclonal antibodies, (mAbs), for use in therapeutic and diagnostic applications has not been fully realized in part due to counter-immune responses that often arise in patient recipients of mAb...

  15. Antibodies to watch in 2018

    Science.gov (United States)

    Kaplon, Hélène; Reichert, Janice M.

    2018-01-01

    ABSTRACT The pace of antibody therapeutics development accelerated in 2017, and this faster pace is projected to continue through 2018. Notably, the annual number of antibody therapeutics granted a first approval in either the European Union (EU) or United States (US) reached double-digits (total of 10) for the first time in 2017. The 10 antibodies granted approvals are: brodalumab, dupilumab, sarilumab, guselkumab, benralizumab, ocrelizumab, inotuzumab ozogamicin, avelumab, duvalumab, and emicizumab. Brodalumab, however, had already been approved in Japan in 2016. As of December 1, 2017, nine antibody therapeutics (ibalizumab, burosumab, tildrakizumab, caplacizumab, erenumab, fremanezumab, galcanezumab, romosozumab, mogamulizumab) were in regulatory review in the EU or US, and regulatory actions on their marketing applications are expected by the end of 2018. Based on company announcements and estimated clinical study primary completion dates, and assuming the study results are positive, marketing applications for at least 12 antibody therapeutics that are now being evaluated in late-stage clinical studies may be submitted by the end of 2018. Of the 12 candidates, 8 are for non-cancer indications (lanadelumab, crizanlizumab, ravulizumab, eptinezumab, risankizumab, satralizumab, brolucizumab, PRO140) and 4 are for cancer (sacituzumab govitecan, moxetumomab pasudotox, cemiplimab, ublituximab). Additional antibody therapeutics to watch in 2018 include 19 mAbs undergoing evaluation in late-stage studies with primary completion dates in late 2017 or during 2018. Of these mAbs, 9 are for non-cancer indications (lampalizumab, roledumab, emapalumab, fasinumab, tanezumab, etrolizumab, NEOD001, gantenerumab, anifrolumab) and 10 are for cancer indications (tremelimumab, isatuximab, BCD-100, carotuximab, camrelizumab, IBI308, glembatumumab vedotin, mirvetuximab soravtansine, oportuzumab monatox, L19IL2/L19TNF). Positive clinical study results may enable marketing application

  16. Monoclonal antibodies technology. Protocols

    International Nuclear Information System (INIS)

    Acevado Castro, B.E.

    1997-01-01

    Full text: Immunization. The first step in preparing useful monoclonal antibodies (MAbs) is to immunize an animal (Balb/c for example) with an appropriate antigen. Methods (only for soluble antigen): Solubilize selected antigen in Phosphate buffer solution (PBS) at pH 7.2-7.4, ideally at a final concentration per animal between 10 to 50 μg/ml. It is recommended that the antigen under consideration be incorporated into the emulsion adjuvants in 1:1 volumetric relation. We commonly use Frend's adjuvant (FA) to prepared immunized solution. The first immunization should be prepared with complete FA, and the another could be prepared with incomplete FA. It is recommended to inject mice with 0.2 ml intraperitoneal (ip) or subcutaneous (sc). Our experience suggests the sc route is the preferred route. A minimum protocol for immunizing mice to generate cells for preparing hybridomas is s follows: immunize sc on day 0, boost sc on day 21, take a trial bleeding on day 26; if antibody titters are satisfactory, boost ip on day 35 with antigen only, and remove the spleen to obtain cells for fusion on day 38. Fusion protocol. The myeloma cell line we are using is X63 Ag8.653. At the moment of fusion myeloma cells need a good viability (at least a 95%). 1. Remove the spleen cells from immunized mice using sterile conditions. An immune spleen should yield between 7 a 10x10 7 nucleated cells. 2. Place the spleen in 20 ml of serum-free RPMI 1640 in a Petri dish. Using a needle and syringe, inject the spleen with medium to distend and disrupt the spleen stroma and free the nucleated cells. 3. Flush the cell suspension with a Pasteur pipet to disperse clumps of cells. 4. Centrifuge the spleen cell suspension at 250g for 10 min. Resuspend the pellet in serum-free RPMI 1640. Determine cell concentration using Neuhabuer chamber. 5. Mix the myeloma cells and spleen cells in a conical 50-ml tube in serum-free RPMI 1640, 1 x10 7 spleen cells to 1x10 6 myeloma cells (ratio 10:1). Centrifuge

  17. Tabhu: tools for antibody humanization.

    KAUST Repository

    Olimpieri, Pier Paolo

    2014-10-09

    SUMMARY: Antibodies are rapidly becoming essential tools in the clinical practice, given their ability to recognize their cognate antigens with high specificity and affinity, and a high yield at reasonable costs in model animals. Unfortunately, when administered to human patients, xenogeneic antibodies can elicit unwanted and dangerous immunogenic responses. Antibody humanization methods are designed to produce molecules with a better safety profile still maintaining their ability to bind the antigen. This can be accomplished by grafting the non-human regions determining the antigen specificity into a suitable human template. Unfortunately, this procedure may results in a partial or complete loss of affinity of the grafted molecule that can be restored by back-mutating some of the residues of human origin to the corresponding murine ones. This trial-and-error procedure is hard and involves expensive and time-consuming experiments. Here we present tools for antibody humanization (Tabhu) a web server for antibody humanization. Tabhu includes tools for human template selection, grafting, back-mutation evaluation, antibody modelling and structural analysis, helping the user in all the critical steps of the humanization experiment protocol. AVAILABILITY: http://www.biocomputing.it/tabhu CONTACT: anna.tramontano@uniroma1.it, pierpaolo.olimpieri@uniroma1.it SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

  18. Antibodies to watch in 2014.

    Science.gov (United States)

    Reichert, Janice M

    2014-01-01

    Since 2010, mAbs has documented the biopharmaceutical industry's progress in transitioning antibody therapeutics to first Phase 3 clinical studies and regulatory review, and its success at gaining first marketing approvals for antibody-based products. This installment of the "Antibodies to watch" series outlines events anticipated to occur between December 2013 and the end of 2014, including first regulatory actions on marketing applications for vedolizumab, siltuximab, and ramucirumab, as well as the Fc fusion proteins Factor IX-Fc and Factor VIII-Fc; and the submission of first marketing applications for up to five therapeutics (secukinumab, ch14.18, onartuzumab, necitumumab, gevokizumab). Antibody therapeutics in Phase 3 studies are described, with an emphasis on those with study completion dates in 2014, including antibodies targeting interleukin-17a or the interleukin-17a receptor (secukinumab, ixekizumab, brodalumab), proprotein convertase subtilisin/kexin type 9 (alirocumab, evolocumab, bococizumab), and programmed death 1 receptor (lambrolizumab, nivolumab). Five antibodies with US Food and Drug Administration's Breakthrough Therapy designation (obinutuzumab, ofatumumab, lambrolizumab, bimagrumab, daratumumab) are also discussed.

  19. Avian Diagnostic and Therapeutic Antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, David Sherman [UND SMHS

    2012-12-31

    A number of infectious agents have the potential of causing significant clinical symptomology and even death, but dispite this, the number of incidence remain below the level that supports producing a vaccine. Therapeutic antibodies provide a viable treatment option for many of these diseases. We proposed that antibodies derived from West Nile Virus (WNV) immunized geese would be able to treat WNV infection in mammals and potential humans. We demonstrated that WNV specific goose antibodies are indeed successful in treating WNV infection both prophylactically and therapeutically in a golden hamster model. We demonstrated that the goose derived antibodies are non-reactogenic, i.e. do not cause an inflammatory response with multiple exposures in mammals. We also developed both a specific pathogen free facility to house the geese during the antibody production phase and a patent-pending purification process to purify the antibodies to greater than 99% purity. Therefore, the success of these study will allow a cost effective rapidly producible therapeutic toward clinical testing with the necessary infrastructure and processes developed and in place.

  20. Radiolabeled monoclonal antibodies: a review

    International Nuclear Information System (INIS)

    Toledo e Souza, I.T. de; Okada, H.

    1990-05-01

    Since the description by Kohler and Milstein 1975 of their technique for producing monoclonal antibodies of predefined specificity, it has become a mainstay in most laboratories that utilize immunochemical techniques to study problems in basic, applied or clinical research. Paradoxically, the very success of monoclonal antibodies has generated a literature which is now so vast and scattered that it has become difficult to obtain a perspective. This brief review represents the distillation of many publications relating to the production and use of monoclonaal antibodies as radiopharmaceuticals. Significant advances were made possible in the last few years by combined developments in the fields of tumor-associated antigens and of monoclonal antibodies. In fact monoclonal antibodies against some well defined tumor-associated antigens, has led to significantly greater practical possibilities for producing highly specific radiolabeled antibodies as radiopharmaceuticals for diagnosis and therapy of human tumors. One of the main requirements of this methodology is the availability of stable radiopharmaceutical reagents which after labeling in vivo injection retain the capacity of specific interaction with the defined antigen and their molecular integrity. Since injection into human is the objetive of this kind of study all the specifications of radiopharmaceutical have to be fulfilled e.g. sterility, apirogenicity and absence of toxicity. (author) [pt

  1. Method of stably radiolabeling antibodies with technetium and rhenium

    International Nuclear Information System (INIS)

    Paik, C.H.; Reba, R.C.; Eckelman, W.C.

    1987-01-01

    A method is described for labeling antibodies or antibody fragments with radionuclides of technetium or rhenium to obtain stable labeling, comprising: reacting a reduced radioisotope of technetium or rhenium with an antibody or antibody fragment, or a diethylenetriaminepentaacetic acid conjugated antibody or antibody fragment, in the presence of free or carrier-bound diethylenetriaminepentaacetic acid (DTPA). The amount of DTPA is sufficient to substantially completely inhibit binding of the reduced technetium or rhenium to nonstable binding sites of the antibody or antibody fragment, or the DTPA-conjugated antibody or antibody fragment. The resultant stably labeled antibody or antibody fragment, or DTPA[conjugated antibody or antibody fragment is recovered

  2. Detection of serum anti-B/B’ UsnRNP antibodies in patients with connective tissue diseases by immunoblotting

    Directory of Open Access Journals (Sweden)

    L. Iaccarino

    2011-09-01

    Full Text Available Objective: To investigate the reliability of the immunoblot method in the detection of serum immunoreactivity towards the B/B’ polypeptides of U small nuclear ribonucleoproteins (UsnRNP and to assess the significance of these antibodies in connective tissue disease (CTD patients. Methods: We tested the sera of 348 patients with CTD (101 SLE, 51 systemic sclerosis, 53 primary Sjogren’s syndrome, 27 poly/dermatomyositis, 15 rheumatoid arthritis and 101 overlap CTD, of 31 matched healthy subjects and 13 patients with primary Epstein-Barr virus (EBV infection with high titre IgG anti-EBV antibodies. IgG anti-UsnRNP antibodies were determined by immunoblotting on nuclear extract from Raji cells (an EBV-immortalised human B lymphoid cell line and Jurkat cells (a human T lymphoid cell line. Anti-dsDNA antibodies were detected by indirect immunofluorescence on Crithidia luciliae and anti-ENA by counterimmunoelectrophoresis. Anti-dsDNA activity and avidity were measured in SLE sera by ELISA with Scatchard analysis. Results were statistically analysed by chi-square and Mann-Whitney tests. Results: A high frequency of anti-B/B’ antibodies was found in the sera of CTD patients, confined to SLE (54.4% and overlap CTD with SLE features (55,2%. Anti-B/B’ immune reactivity was closely associated with other anti-UsnRNP specificities, gel precipitating anti-nRNP and anti-P antibodies. Nine out of 15 (60% anti-B/B’ positive/anti-ENA negative lupus sera on Raji blots were confirmed to be positive also on Jurkat blots. The sera from patients with EBV infection provided, on Raji blots, completely different band patterns from those obtained with auto-immune sera. Conclusions. The Sm B/B’ proteins are the predominant or, at least, the most frequently targeted antigens of the UsnRNP auto-immune response in SLE and “lupus-like” overlap CTD. Moreover, anti-B/B’ is diagnostically specific for CTD with SLE features. Immunoblotting on human B lymphoid cells

  3. Radioiodination of antibodies for tumor imaging

    International Nuclear Information System (INIS)

    Saha, G.B.

    1983-01-01

    In view of the great potential of radioiodinated antibody for the detection and treatment of cancer, the present article deals with the various techniques of radioiodination of antibody and their uses. Topics include methods of iodination of antibody, advantages and disadvantages of different methods, and effects of radioiodination on the antibody molecules with respect to their physiochemical and immunologic reactivity. In addition, the clinical usefulness of radioiodinated antibodies is discussed. (Auth.)

  4. Antibodies from plants for bionanomaterials.

    Science.gov (United States)

    Edgue, Gueven; Twyman, Richard M; Beiss, Veronique; Fischer, Rainer; Sack, Markus

    2017-11-01

    Antibodies are produced as part of the vertebrate adaptive immune response and are not naturally made by plants. However, antibody DNA sequences can be introduced into plants, and together with laboratory technologies that allow the design of antibodies recognizing any conceivable molecular structure, plants can be used as 'green factories' to produce any antibody at all. The advent of plant-based transient expression systems in particular allows the rapid, convenient, and safe production of antibodies, ranging from laboratory-scale expression to industrial-scale manufacturing. The key features of plant-based production include safety, speed, low cost, and convenience, allowing newcomers to rapidly master the technology and use it to its full advantage. Manufacturing in plants has recently achieved significant milestones and offers more than just an alternative to established microbial and mammalian cell platforms. The use of plants for product development in particular offers the power and flexibility to easily coexpress many different genes, allowing the plug-and-play construction of novel bionanomaterials, perfectly complementing existing approaches based on plant virus-like particles. As well as producing single antibodies for applications in medicine, agriculture, and industry, plants can be used to produce antibody-based supramolecular structures and scaffolds as a new generation of green bionanomaterials that promise a bright future based on clean and renewable nanotechnology applications. WIREs Nanomed Nanobiotechnol 2017, 9:e1462. doi: 10.1002/wnan.1462 For further resources related to this article, please visit the WIREs website. © 2017 The Authors. WIREs Nanomedicine and Nanobiotechnology published by Wiley Periodicals, Inc.

  5. Monoclonal antibody hapten radiopharmaceutical delivery

    International Nuclear Information System (INIS)

    Goodwin, D.A.; McTigue, M.

    1986-01-01

    One hundred μg of monoclonal antibody (MoAb) CHA255 with a binding constant Kb of 4 x 10 9 was complexed with indium-111 labelled BLEDTA II, BLEDTA IV, benzyl EDTA, and an EDTA conjugate of Fab. The 24-h tumour and organ distribution of BALB/c mice bearing KHJJ tumours was studied for each compound alone, the antibody complex, and 3 h following a chelate chase of the antibody complex. Whole body biological half-life was measured for 7 days with and without a chelate chase for each antibody complex. The 24-h whole body counts dropped 20 to 60% and blood concentration fell over 89% within 3 h of administering the chelate chase. Theoretical equivalent human organ doses were calculated from the 24-h organ concentrations, effective half-life, and MIRD 11 S values (absorbed dose per cumulated activity). Liver and spleen were the target organs, with the dose ranging from 0.50 to 3.91 rads mCi -1 . The reduction in organ radiation dose varied up to 95% following the chelate chase. Rapid selective renal clearance of chelate labelled radiopharmaceuticals by competitive inhibition (chelate chase) of their reversible binding to monoclonal antibodies enhances tumour imaging and improves the radiation dosimetry. (author)

  6. Uses of monoclonal antibody 8H9

    Science.gov (United States)

    Cheung, Nai-Kong V.

    2013-04-09

    This invention provides a composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a suitable carrier. This invention provides a pharmaceutical composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a pharmaceutically acceptable carrier. This invention also provides an antibody other than the monoclonal antibody 8H9 comprising the complementary determining regions of monoclonal antibody 8H9 or a derivative thereof, capable of binding to the same antigen as the monoclonal antibody 8H9. This invention provides a substance capable of competitively inhibiting the binding of monoclonal antibody 8H9. This invention also provides an isolated scFv of monoclonal antibody 8H9 or a derivative thereof. This invention also provides the 8H9 antigen. This invention also provides different uses of the monoclonal antibody 8H9 or its derivative.

  7. Complement-mediated bactericidal activity of anti-factor H binding protein monoclonal antibodies against the meningococcus relies upon blocking factor H binding.

    Science.gov (United States)

    Giuntini, Serena; Reason, Donald C; Granoff, Dan M

    2011-09-01

    Binding of the complement-downregulating protein factor H (fH) to the surface of the meningococcus is important for survival of the organism in human serum. The meningococcal vaccine candidate factor H binding protein (fHbp) is an important ligand for human fH. While some fHbp-specific monoclonal antibodies (MAbs) block binding of fH to fHbp, the stoichiometry of blocking in the presence of high serum concentrations of fH and its effect on complement-mediated bactericidal activity are unknown. To investigate this question, we constructed chimeric antibodies in which the human IgG1 constant region was paired with three murine fHbp-specific binding domains designated JAR 3, JAR 5, and MAb502. By surface plasmon resonance, the association rates for binding of all three MAbs to immobilized fHbp were >50-fold higher than that for binding of fH to fHbp, and the MAb dissociation rates were >500-fold lower than that for fH. While all three MAbs elicited similar C1q-dependent C4b deposition on live bacteria (classical complement pathway), only those antibodies that inhibited binding of fH to fHbp (JAR 3 and JAR 5) had bactericidal activity with human complement. MAb502, which did not inhibit fH binding, had complement-mediated bactericidal activity only when tested with fH-depleted human complement. When an IgG1 anti-fHbp MAb binds to sparsely exposed fHbp on the bacterial surface, there appears to be insufficient complement activation for bacteriolysis unless fH binding also is inhibited. The ability of fHbp vaccines to elicit protective antibodies, therefore, is likely to be enhanced if the antibody repertoire is of high avidity and includes fH-blocking activity.

  8. Refolding Technologies for Antibody Fragments

    Directory of Open Access Journals (Sweden)

    Tsutomu Arakawa

    2014-05-01

    Full Text Available Refolding is one of the production technologies for pharmaceutical grade antibody fragments. Detergents and denaturants are primarily used to solubilize the insoluble proteins. The solubilized and denatured proteins are refolded by reducing the concentration of the denaturants or detergents. Several refolding technologies have been used for antibody fragments, comprising dilution, dialysis, solid phase solvent exchange and size exclusion chromatography, as reviewed here. Aggregation suppressor or folding-assisting agents, including arginine hydrochloride, ionic liquids and detergents or denaturants at low concentrations, are included in the refolding solvent to enhance refolding yield.

  9. Serum Antibody Biomarkers for ASD

    Science.gov (United States)

    2015-10-01

    typically developing control. US, unaffected sibling control. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a...typically developing (TD) children (e.g., Warren et al., 1990; Singh, 2009). The goal of this study is to identify a serum antibody biomarker for ASD using...50% less IgG1 antibody in ASD boys vs . TD boys (p=0.0096). The level of ASD1 binding to the AM group was the same as to the ASD boys. These data

  10. Monoclonal antibody-based immunoassays.

    Science.gov (United States)

    Appleby, P; Reischl, U

    1998-01-01

    An immunoassay may be defined as an assay that employs an immunological reagent, usually an antibody, to confer specificity for the ligand being measured. As a corollary to this, the discovery, and subsequent development, of monoclonal antibodies (MAbs) has greatly expanded the application and use of immunoassays. Polyclonal reagents, with their associated problems of specificity and quality control, have now been largely replaced by readily available MAbs of potential immortality and well-defined specificity and affinity. This has resulted, in the last two decades, in a great expansion in the range of immunoassays available and also a significant improvement in their reproducibility and reliability.

  11. Antibody profiling sensitivity through increased reporter antibody layering

    Science.gov (United States)

    Apel, William A; Thompson, Vicki S

    2013-02-26

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  12. Antibody profiling sensitivity through increased reporter antibody layering

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William A.; Thompson, Vicki S.

    2017-03-28

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  13. Antibody profiling sensitivity through increased reporter antibody layering

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William A.; Thompson, Vicki S.

    2013-02-26

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  14. Antibody profiling sensitivity through increased reporter antibody layering

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William A.; Thompson, Vicki S

    2010-04-13

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  15. Tumor detection using radiolabeled monoclonal antibodies

    International Nuclear Information System (INIS)

    Moldofsky, P.J.; Powe, J.; Hammond, N.D.

    1987-01-01

    Radioisotope conjugated to monoclonal antibody products has been used for imaging tumors targeted by the antibody. As imaging progresses, new sets of procedural and technical questions arise. In this chapter, we discuss several current problems in imaging tumor with radiolabeled monoclonal antibody. These include (1) methods for selection of specific antibody and, once the particular antibody is selected, which fragment form is to be used; (2) imaging procedures: what are the optimum imaging parameters, such as optimum time for imaging after administration of tracer and considerations regarding background subtraction; and (3) noninvasive quantitative techniques: quantitation of localization of antibody indirectly from quantitative information in the images.100 references

  16. Bispecific antibodies targeting human CD73

    DEFF Research Database (Denmark)

    2017-01-01

    The present invention relates to a bispecific antibody targeting CD73. In particular, the present invention relates to a bispecific antibody targeting different epitopes on CD73 or a bispecific antibody targeting an epitope on CD73 and an epitope on a different antigen.......The present invention relates to a bispecific antibody targeting CD73. In particular, the present invention relates to a bispecific antibody targeting different epitopes on CD73 or a bispecific antibody targeting an epitope on CD73 and an epitope on a different antigen....

  17. Participation of L3T4 in T cell activation in the absence of class II major histocompatibility complex antigens. Inhibition by anti-L3T4 antibodies is a function both of epitope density and mode of presentation of anti-receptor antibody

    DEFF Research Database (Denmark)

    Owens, T; Fazekas de St Groth, B

    1987-01-01

    two monoclonal antibodies, KJ16-133.18 and F23.1, that recognize a determinant encoded by the T cell receptor V beta 8 gene family. These antibodies were used to select two clones of T cells with surface phenotype Thy-1.2+, L3T4+, Lyt-2-, KJ16-133.18+, F23.1+, IA-, IE-. One of these clones (E9.D4......The recognition of many class II major histocompatibility complex (MHC)-associated antigens by T cells requires the participation of the L3T4 molecule. It has been proposed that this molecule acts to stabilize low affinity binding to antigen in association with MHC and thereby increases the avidity...... of T cell/antigen interactions. By using antibodies against the T cell antigen receptor (TCR) to activate T cells, thereby circumventing the requirement for antigen presenting cells and MHC-associated antigen, we have been able to study the function of L3T4 in the absence of class II MHC. We have used...

  18. Quantifying the importance of MSP1-19 as a target of growth-inhibitory and protective antibodies against Plasmodium falciparum in humans.

    Directory of Open Access Journals (Sweden)

    Danny W Wilson

    Full Text Available BACKGROUND: Antibodies targeting blood stage antigens are important in protection against malaria, but the key targets and mechanisms of immunity are not well understood. Merozoite surface protein 1 (MSP1 is an abundant and essential protein. The C-terminal 19 kDa region (MSP1-19 is regarded as a promising vaccine candidate and may also be an important target of immunity. METHODOLOGY/FINDINGS: Growth inhibitory antibodies against asexual-stage parasites and IgG to recombinant MSP1-19 were measured in plasma samples from a longitudinal cohort of 206 children in Papua New Guinea. Differential inhibition by samples of mutant P. falciparum lines that expressed either the P. falciparum or P. chabaudi form of MSP1-19 were used to quantify MSP1-19 specific growth-inhibitory antibodies. The great majority of children had detectable IgG to MSP1-19, and high levels of IgG were significantly associated with a reduced risk of symptomatic P. falciparum malaria during the 6-month follow-up period. However, there was little evidence of PfMSP1-19 specific growth inhibition by plasma samples from children. Similar results were found when testing non-dialysed or dialysed plasma, or purified antibodies, or when measuring growth inhibition in flow cytometry or microscopy-based assays. Rabbit antisera generated by immunization with recombinant MSP1-19 demonstrated strong MSP1-19 specific growth-inhibitory activity, which appeared to be due to much higher antibody levels than human samples; antibody avidity was similar between rabbit antisera and human plasma. CONCLUSIONS/SIGNIFICANCE: These data suggest that MSP1-19 is not a major target of growth inhibitory antibodies and that the protective effects of antibodies to MSP1-19 are not due to growth inhibitory activity, but may instead be mediated by other mechanisms. Alternatively, antibodies to MSP1-19 may act as a marker of protective immunity.

  19. Evolution of Soybean mosaic virus-G7 molecularly cloned genome in Rsv1-genotype soybean results in emergence of a mutant capable of evading Rsv1-mediated recognition

    International Nuclear Information System (INIS)

    Hajimorad, M.R.; Eggenberger, A.L.; Hill, J.H.

    2003-01-01

    Plant resistance (R) genes direct recognition of pathogens harboring matching avirluent signals leading to activation of defense responses. It has long been hypothesized that under selection pressure the infidelity of RNA virus replication together with large population size and short generation times results in emergence of mutants capable of evading R-mediated recognition. In this study, the Rsv1/Soybean mosaic virus (SMV) pathosystem was used to investigate this hypothesis. In soybean line PI 96983 (Rsv1), the progeny of molecularly cloned SMV strain G7 (pSMV-G7) provokes a lethal systemic hypersensitive response (LSHR) with up regulation of a defense-associated gene transcript (PR-1). Serial passages of a large population of the progeny in PI 96983 resulted in emergence of a mutant population (vSMV-G7d), incapable of provoking either Rsv1-mediated LSHR or PR-1 protein gene transcript up regulation. An infectious clone of the mutant (pSMV-G7d) was synthesized whose sequences were very similar but not identical to the vSMV-G7d population; however, it displayed a similar phenotype. The genome of pSMV-G7d differs from parental pSMV-G7 by 17 substitutions, of which 10 are translationally silent. The seven amino acid substitutions in deduced sequences of pSMV-G7d differ from that of pSMV-G7 by one each in P1 proteinase, helper component-proteinase, and coat protein, respectively, and by four in P3. To the best of our knowledge, this is the first demonstration in which experimental evolution of a molecularly cloned plant RNA virus resulted in emergence of a mutant capable of evading an R-mediated recognition

  20. Polyclonal and monoclonal antibodies in clinic.

    Science.gov (United States)

    Wootla, Bharath; Denic, Aleksandar; Rodriguez, Moses

    2014-01-01

    Immunoglobulins (Ig) or antibodies are heavy plasma proteins, with sugar chains added to amino-acid residues by N-linked glycosylation and occasionally by O-linked glycosylation. The versatility of antibodies is demonstrated by the various functions that they mediate such as neutralization, agglutination, fixation with activation of complement and activation of effector cells. Naturally occurring antibodies protect the organism against harmful pathogens, viruses and infections. In addition, almost any organic chemical induces antibody production of antibodies that would bind specifically to the chemical. These antibodies are often produced from multiple B cell clones and referred to as polyclonal antibodies. In recent years, scientists have exploited the highly evolved machinery of the immune system to produce structurally and functionally complex molecules such as antibodies from a single B clone, heralding the era of monoclonal antibodies. Most of the antibodies currently in the clinic, target components of the immune system, are not curative and seek to alleviate symptoms rather than cure disease. Our group used a novel strategy to identify reparative human monoclonal antibodies distinct from conventional antibodies. In this chapter, we discuss the therapeutic relevance of both polyclonal and monoclonal antibodies in clinic.

  1. Purification of immunoreactive radiolabeled moniclonal antibodies with anti-iodiotypic moniclonal antibodies

    International Nuclear Information System (INIS)

    Temponi, M.; Pupa, S.; Ferrone, S.

    1990-01-01

    A method is described to purify immunoreactive moniclonal antibodies from radiolabeled monoclonal antibody preparations. The method is based on incubation of radiolabeled monoclonal antibodies with insolubilized anti-idiotypic monoclonal antibodies to idiotopes within the antigen-combining site of monoclonal antibodies to be purified an elution of bound monoclonal antibodies with a low pH buffer. The immunoreactive fraction of the purified monoclonal antibodies was at least 82%; the yeald was at least 73%. The purification procedure did not cause any detectable change in the affinity constant of the eluted monoclonal antibodies. The method is simple and rapid; the requirement for anti-idiotypic monoclonal antibodies to idiotopes within the antigen-combining site of the antibodies to be purified is not likely to represent a major limitation in the broad application of the present method, since the hybridoma technology has greatly facilitated the development of anti-idiotypic monoclonal antibodies. (author). 12 refs.; 4 figs.; 1 tab

  2. Dengue antibodies in blood donors.

    Science.gov (United States)

    Ribas-Silva, Rejane Cristina; Eid, Andressa Ahmad

    2012-01-01

    Dengue is an urban arbovirus whose etiologic agent is a virus of the genus Flavorius with four distinct antigen serotypes (DENV-1, DENV-2, DENV-3 and DENV-4) that is transmitted to humans through the bite of the mosquito Aedes aegypti. The Campo Mourão region in Brazil is endemic for dengue fever. OBTECTIVE: The aim of this study was to evaluate the presence of IgG and IgM antibodies specific to the four serotypes of dengue in donors of the blood donor service in the city of Campo Mourão. Epidemiological records were evaluated and 4 mL of peripheral blood from 213 blood donors were collected in tubes without anticoagulant. Serum was then obtained and immunochromatographic tests were undertaken (Imuno-Rápido Dengue IgM/IgG(TM)). Individuals involved in the study answered a social and epidemiological questionnaire on data which included age, gender and diagnosis of dengue. Only three (1.4%) of the 213 blood tests were positive for IgG anti-dengue antibodies. No donors with IgM antibody, which identifies acute infection, were identified. The results of the current analysis show that the introduction of quantitative or molecular serological methods to determine the presence of anti-dengue antibodies or the detection of the dengue virus in blood donors in endemic regions should be established so that the quality of blood transfusions is guaranteed.

  3. Somatic and recombinant monoclonal antibodies for the diagnosis and therapy of drug unresponsive tumors

    International Nuclear Information System (INIS)

    Cianfriglia, M.

    2009-01-01

    Multiple reasons can explain the lack of clinical efficacy of chemotherapy. Among these, the intrinsic or acquired multidrug resistance (MDR) phenotype of tumor cells remain the major obstacles of successful pharmacological treatment of cancer. To circumvent this problem we developed several strategies which include: 1.) isolation of human monoclonal antibodies to tumour-associated antigen using an innovative biotechnological approach; 2.) genetic construction and expression of immuno-competent fusion protein to deliver enzymatic activities to tumor tissues to convert relatively non-toxic prodrugs into more active chemotherapeutic agents; 3.) identification of new chemical compounds capable to revert the MDR phenotype of tumor cells thus rendering drug resistant cancer de novo susceptible to chemotherapy; 4.) development and pre-clinical assay of novel anti tumor compounds with a high therapeutic index and evading the drug efflux mechanisms of the MDR1-P-glycoprotein (MDR1-Pgp) and the multidrug resistance-associated protein 1 (MRP1)which are often regarded as the prototypes of the cell-based mechanisms of MDR and failure of chemotherapy

  4. Multivalent Porous Silicon Nanoparticles Enhance the Immune Activation Potency of Agonistic CD40 Antibody

    Science.gov (United States)

    Gu, Luo; Ruff, Laura E.; Qin, Zhengtao; Corr, Maripat P.; Hedrick, Stephen M.; Sailor, Michael J.

    2012-01-01

    One of the fundamental paradigms in the use of nanoparticles to treat disease is to evade or suppress the immune system in order to minimize systemic side effects and deliver sufficient nanoparticle quantities to the intended tissues. However, the immune system is the body's most important and effective defense against diseases. It protects the host by identifying and eliminating foreign pathogens as well as selfmalignancies. Here we report a nanoparticle engineered to work with the immune system, enhancing the intended activation of antigen presenting cells (APCs). We show that luminescent porous silicon nanoparticles (LPSiNPs), each containing multiple copies of an agonistic antibody (FGK45) to the APC receptor CD40, greatly enhance activation of B cells. The cellular response to the nanoparticle-based stimulators is equivalent to a 30–40 fold larger concentration of free FGK45. The intrinsic near-infrared photoluminescence of LPSiNPs is used to monitor degradation and track the nanoparticles inside APCs. PMID:22689074

  5. Progranulin antibodies in autoimmune diseases.

    Science.gov (United States)

    Thurner, Lorenz; Preuss, Klaus-Dieter; Fadle, Natalie; Regitz, Evi; Klemm, Philipp; Zaks, Marina; Kemele, Maria; Hasenfus, Andrea; Csernok, Elena; Gross, Wolfgang L; Pasquali, Jean-Louis; Martin, Thierry; Bohle, Rainer Maria; Pfreundschuh, Michael

    2013-05-01

    Systemic vasculitides constitute a heterogeneous group of diseases. Autoimmunity mediated by B lymphocytes and their humoral effector mechanisms play a major role in ANCA-associated vasculitis (AAV) as well as in non-ANCA associated primary systemic vasculitides and in the different types of autoimmune connective tissue disorders and rheumatoid arthritis. In order to detect autoantibodies in systemic vasculitides, we screened protein macroarrays of human cDNA expression libraries with sera from patients with ANCA-associated and ANCA-negative primary systemic vasculitides. This approach led to the identification of antibodies against progranulin, a 88 kDA secreted glycoprotein with strong anti-inflammatory activity in the course of disease of giant-cell arteritis/polymyalgia rheumatica (14/65), Takayasu's arteritis (4/13), classical panarteritis nodosa (4/10), Behcet's disease (2/6) and in the course of disease in granulomatosis with polyangiitis (31/75), Churg-Strauss syndrome (7/23) and in microscopic polyangiitis (7/19). In extended screenings the progranulin antibodies were also detected in other autoimmune diseases such as systemic lupus erythematosus (39/91) and rheumatoid arthritis (16/44). Progranulin antibodies were detected only in 1 of 97 healthy controls. Anti-progranulin positive patients with systemic vasculitides, systemic lupus erythematosus or rheumatoid arthritis had significant lower progranulin plasma levels, indicating a neutralizing effect. In light of the anti-inflammatory effects of progranulin, progranulin antibodies might exert pro-inflammatory effects thus contributing to the pathogenesis of the respective autoimmune diseases and might serve as a marker for disease activity. This hypothesis is supported by the fact that a positive progranulin antibody status was associated with active disease in granulomatosis with polyangiitis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Multiplex serology of paraneoplastic antineuronal antibodies

    NARCIS (Netherlands)

    P. Maat (Peter); E. Brouwer (Eric); E. Hulsenboom (Esther); M.M. van Duijn (Martijn); M.W.J. Schreurs (Marco); H. Hooijkaas (Herbert); P.A. Smitt (Peter)

    2013-01-01

    textabstractParaneoplastic neurological syndromes (PNS) are devastating neurological disorders secondary to cancer, associated with onconeural autoantibodies. Such antibodies are directed against neuronal antigens aberrantly expressed by the tumor. The detection of onconeural antibodies in a patient

  7. Alternative affinity tools: more attractive than antibodies?

    NARCIS (Netherlands)

    Ruigrok, V.J.B.; Levisson, M.; Eppink, M.H.M.; Smidt, H.; Oost, van der J.

    2011-01-01

    Antibodies are the most successful affinity tools used today, in both fundamental and applied research (diagnostics, purification and therapeutics). Nonetheless, antibodies do have their limitations, including high production costs and low stability. Alternative affinity tools based on nucleic acids

  8. [Neuroimmunological diseases associated with VGKC complex antibodies].

    Science.gov (United States)

    Watanabe, Osamu

    2013-05-01

    Antibodies to voltage-gated potassium channels(VGKC) were first identified by radioimmunoassay of radioisotope labeled alpha-dendrotoxin-VGKCs solubilized from rabbit brain. These antibodies were found only in a proportion of patients with acquired neuromyotonia (Isaacs' syndrome). VGKC antibodies were also detected in Morvan's syndrome and in a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC" antibodies are mainly directed toward associated proteins(for example LGI-1, Caspr-2) that complex with the VGKCs themselves. The "VGKC" antibodies are now usually known as VGKC-complex antibodies. In general, LGI-1 antibodies are most common in limbic encephalitis with SIADH. Caspr-2 antibodies are present in the majority of patients with Morvan's syndrome. These patients develop combinations of CNS symptoms, autonomic dysfunction, and peripheral nerve hyperexcitability.

  9. Synthesis of Tumor-avid Photosensitizer-Gd(III)DTPA conjugates: impact of the number of gadolinium units in T1/T2 relaxivity, intracellular localization, and photosensitizing efficacy.

    Science.gov (United States)

    Goswami, Lalit N; White, William H; Spernyak, Joseph A; Ethirajan, Manivannan; Chen, Yihui; Missert, Joseph R; Morgan, Janet; Mazurchuk, Richard; Pandey, Ravindra K

    2010-05-19

    To develop novel bifunctional agents for tumor imaging (MR) and photodynamic therapy (PDT), certain tumor-avid photosensitizers derived from chlorophyll-a were conjugated with variable number of Gd(III)aminobenzyl DTPA moieties. All the conjugates containing three or six gadolinium units showed significant T(1) and T(2) relaxivities. However, as a bifunctional agent, the 3-(1'-hexyloxyethyl)pyropheophorbide-a (HPPH) containing 3Gd(III) aminophenyl DTPA was most promising with possible applications in tumor-imaging and PDT. Compared to HPPH, the corresponding 3- and 6Gd(III)aminobenzyl DTPA conjugates exhibited similar electronic absorption characteristics with a slightly decreased intensity of the absorption band at 660 nm. However, compared to HPPH, the excitation of the broad "Soret" band (near 400 nm) of the corresponding 3Gd(III)aminobenzyl-DTPA analogues showed a significant decrease in the fluorescence intensity at 667 nm.

  10. Radioimmunoassay method for detection of gonorrhea antibodies

    International Nuclear Information System (INIS)

    1975-01-01

    A novel radioimmunoassay for the detection of gonorrhea antibodies in serum is described. A radionuclide is bound to gonorrhea antigens produced by a growth culture. In the presence of gonorrhea antibodies in the serum, an antigen-antibody conjugate is formed, the concentration of which can be measured with conventional radiometric methods. The radioimmunoassay is highly specific

  11. Immunoglobulin G4: an odd antibody

    NARCIS (Netherlands)

    Aalberse, R. C.; Stapel, S. O.; Schuurman, J.; Rispens, T.

    2009-01-01

    Despite its well-known association with IgE-mediated allergy, IgG4 antibodies still have several poorly understood characteristics. IgG4 is a very dynamic antibody: the antibody is involved in a continuous process of half-molecules (i.e. a heavy and attached light-chain) exchange. This process, also

  12. Oligomeric recombinant H5 HA1 vaccine produced in bacteria protects ferrets from homologous and heterologous wild-type H5N1 influenza challenge and controls viral loads better than subunit H5N1 vaccine by eliciting high-affinity antibodies.

    Science.gov (United States)

    Verma, Swati; Dimitrova, Milena; Munjal, Ashok; Fontana, Juan; Crevar, Corey J; Carter, Donald M; Ross, Ted M; Khurana, Surender; Golding, Hana

    2012-11-01

    Recombinant hemagglutinin from influenza viruses with pandemic potential can be produced rapidly in various cell substrates. In this study, we compared the functionality and immunogenicity of bacterially produced oligomeric or monomeric HA1 proteins from H5N1 (A/Vietnam/1203/04) with those of the egg-based licensed subunit H5N1 (SU-H5N1) vaccine in ferrets challenged with homologous or heterologous H5N1 highly pathogenic influenza strains. Ferrets were vaccinated twice with the oligomeric or monomeric rHA1 or with SU-H5N1 (Sanofi Pasteur) emulsified with Titermax adjuvant and were challenged with wild-type homologous (A/Vietnam/1203/04; clade 1) or heterologous (A/Whooperswan/Mongolia/244/2005; clade 2.2) virus. Only the oligomeric rHA1 (not the monomeric rHA1) immunogen and the SU-H5N1 vaccine provided protection against the lethality and morbidity of homologous and heterologous highly pathogenic H5N1. Oligomeric rHA1 generated more cross-neutralizing antibodies and higher levels of serum antibody binding to HA1, with stronger avidity and a better IgG/IgM ratio, than monomeric HA1 and SU-H5N1 vaccines, as determined by surface plasmon resonance (SPR). Importantly, viral loads after heterologous H5N1 challenge were more efficiently controlled in ferrets vaccinated with the oligomeric rHA1 immunogen than in SU-H5N1-vaccinated ferrets. The reduction of viral loads in the nasal washes correlated strongly with higher-avidity antibodies to oligomeric rHA1 derived from H5N1 clade 1 and clade 2.2 viruses, as measured by SPR. This is the first study to show the role of antibody avidity for the HA1 globular head domain in reduction of viral loads in the upper respiratory tract, which could significantly reduce viral transmission.

  13. Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer

    Science.gov (United States)

    Brahmer, Julie R.; Tykodi, Scott S.; Chow, Laura Q.M.; Hwu, Wen-Jen; Topalian, Suzanne L.; Hwu, Patrick; Drake, Charles G.; Camacho, Luis H.; Kauh, John; Odunsi, Kunle; Pitot, Henry C.; Hamid, Omid; Bhatia, Shailender; Martins, Renato; Eaton, Keith; Chen, Shuming; Salay, Theresa M.; Alaparthy, Suresh; Grosso, Joseph F.; Korman, Alan J.; Parker, Susan M.; Agrawal, Shruti; Goldberg, Stacie M.; Pardoll, Drew M.; Gupta, Ashok; Wigginton, Jon M.

    2013-01-01

    BACKGROUND Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host’s immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models. METHODS In this multicenter phase 1 trial, we administered intravenous anti–PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to patients with selected advanced cancers. Anti–PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression. RESULTS As of February 24, 2012, a total of 207 patients — 75 with non–small-cell lung cancer, 55 with melanoma, 18 with colorectal cancer, 17 with renal-cell cancer, 17 with ovarian cancer, 14 with pancreatic cancer, 7 with gastric cancer, and 4 with breast cancer — had received anti–PD-L1 antibody. The median duration of therapy was 12 weeks (range, 2 to 111). Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9% of patients. Among patients with a response that could be evaluated, an objective response (a complete or partial response) was observed in 9 of 52 patients with melanoma, 2 of 17 with renal-cell cancer, 5 of 49 with non–small-cell lung cancer, and 1 of 17 with ovarian cancer. Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up. CONCLUSIONS Antibody-mediated blockade of PD-L1 induced durable tumor regression (objective response rate of 6 to 17%) and prolonged stabilization of disease (rates of 12 to 41% at 24 weeks) in patients with advanced cancers, including non–small-cell lung cancer, melanoma, and renal-cell cancer. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00729664.) PMID:22658128

  14. Antiphospholipid Antibody Induced by Nivolumab

    Directory of Open Access Journals (Sweden)

    Ahmed Aburahma

    2018-01-01

    Full Text Available Nivolumab is a monoclonal antibody against the programmed death protein 1 and is used for patients with advanced melanoma. It is associated with potentially immune-related adverse events, including disorders of the skin, GI tract, and the thyroid; these disorders were successfully treated with prednisone and infliximab. Other immunotherapeutic agents were observed to induce the formation of antiphospholipid antibody (APA including α-interferon and interleukin-2. We present a case of APA development after the third dose of nivolumab in a 71-year-old male with advanced melanoma. The APA was detected after finding a prolonged aPTT; the lupus anticoagulant assay tested positive. The patient was treated with prednisone but, unfortunately, he expired a few days later.

  15. Solid phase double-antibody radioimmunoassay procedure

    International Nuclear Information System (INIS)

    Niswender, G.D.

    1977-01-01

    The present invention is concerned with the radioimmunoassay (RIA) procedure for assaying body fluid content of an antigenic substance which may either be an antigen itself or a hapten capable of being converted, such as by means of reaction with a protein, to an antigenic material. The present invention is concerned with a novel and improved modification of a double-antibody RIA technique in which there is a first antibody that is specific to the antigenic substance suspected to be present in a body fluid from which the assay is intended. The second antibody, however, is not specific to the antigenic substance or analyte, but is an antibody against the first antibody

  16. Antibody Repertoire Development in Swine

    Czech Academy of Sciences Publication Activity Database

    Butler, J. E.; Wertz, N.; Šinkora, Marek

    2017-01-01

    Roč. 5, FEB 17 (2017), s. 255-279 ISSN 2165-8102 R&D Projects: GA ČR GA15-02274S; GA ČR(CZ) GA16-09296S Institutional support: RVO:61388971 Keywords : swine * pre-immune antibody repertoire * ileal Peyer's patches Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 4.708, year: 2016

  17. Development of antibody against sulfamethazine

    International Nuclear Information System (INIS)

    Li Ziying; Xi Wenge; Liu Yibing; Zhang Liling; Guo Weizheng; Han Shiquan

    2004-01-01

    Sulfamethazine (SMT) is widely used to treat bacterial and protozoan infections in food animals. So its residue has been detected in various food products, and in Europe, the tolerance level for sulfonamides in meat and milk is 100 ng/g. To ensure that residues in animal food products do not exceed this limit, a simple, sensitive, and rapid method to determinate their residues in animal tissues is needed. In this paper the development of polyclonal or monoclonal antibodies against sulfamethazine (SMT) and a simplified method to identify residual sulfamethazine by radio immunoassay (RIA) is presented. Polyclonal antibodies (PcAbs) against sulfamethazine (SMT) were obtained by immunizing rabbits with SMT-conjugated bovine serum albumin (BSA). The association constants (Ka) of the PcAbs were higher than 108 and the cross-reactivities with Sulfadiazine(SD), Sulfaquinoxaline(SQX) which were structurally related compounds were lower than 0.05%(RIA). Simultaneous, six strains of hybridoma cell were prepared which can secrete monoclonal antibodies (McAbs) against SMT . The Ka of the McAbs against SMT were higher than 107 and the cross-reactivities with SD, SQX were lower than 0.1%(RIA). (authors)

  18. 9 CFR 113.452 - Erysipelothrix Rhusiopathiae Antibody.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Erysipelothrix Rhusiopathiae Antibody... REQUIREMENTS Antibody Products § 113.452 Erysipelothrix Rhusiopathiae Antibody. Erysipelothrix Rhusiopathiae Antibody is a specific antibody product containing antibodies directed against one or more somatic antigens...

  19. Modification of Antibody Function by Mutagenesis.

    Science.gov (United States)

    Dasch, James R; Dasch, Amy L

    2017-09-01

    The ability to "fine-tune" recombinant antibodies by mutagenesis separates recombinant antibodies from hybridoma-derived antibodies because the latter are locked with respect to their properties. Recombinant antibodies can be modified to suit the application: Changes in isotype, format (e.g., scFv, Fab, bispecific antibodies), and specificity can be made once the heavy- and light-chain sequences are available. After immunoglobulin heavy and light chains for a particular antibody have been cloned, the binding site-namely, the complementarity determining regions (CDR)-can be manipulated by mutagenesis to obtain antibody variants with improved properties. The method described here is relatively simple, uses commercially available reagents, and is effective. Using the pComb3H vector, a commercial mutagenesis kit, PfuTurbo polymerase (Agilent), and two mutagenic primers, a library of phage with mutagenized heavy and light CDR3 can be obtained. © 2017 Cold Spring Harbor Laboratory Press.

  20. Designing two-in-one antibodies.

    Science.gov (United States)

    Valladares, Ignacio Garcia; Espinoza, Luis R

    2009-09-01

    Evaluation of: Bostrom J, Shang-Fan Y, Kan D et al.: Variants of the antibody Herceptin that interact with HER2 and VEGF at the antigen binding site. Science 323, 1610-1614 (2009). The longstanding held notion that one antibody equals one antigen and, hence, one function has been challenged in recent years. Improved technology in antibody production, especially the accumulation of sequence data of immunoglobulin genes and the advent of PCR have made it possible to clone antibody gene repertoires. The current paper provides further challenge to the notion of one antibody = one antigen by developing 'two-in-one' antibodies with an antigen-binding site that binds two distinct proteins with high affinity. A therapeutic variant antibody of Herceptin (Genentech, CA, USA) was isolated that binds the human EGF receptor (HER)2 and also to VEGF. This development may represent a breakthrough discovery and may have significant implications in the therapy of malignant, infectious, allergic and autoimmune disorders.

  1. Acquired Antibody Responses against Plasmodium vivax Infection Vary with Host Genotype for Duffy Antigen Receptor for Chemokines (DARC)

    Science.gov (United States)

    Maestre, Amanda; Muskus, Carlos; Duque, Victoria; Agudelo, Olga; Liu, Pu; Takagi, Akihide; Ntumngia, Francis B.; Adams, John H.; Sim, Kim Lee; Hoffman, Stephen L.; Corradin, Giampietro; Velez, Ivan D.; Wang, Ruobing

    2010-01-01

    Background Polymorphism of the Duffy Antigen Receptor for Chemokines (DARC) is associated with susceptibility to and the severity of Plasmodium vivax malaria in humans. P. vivax uses DARC to invade erythrocytes. Individuals lacking DARC are ‘resistant’ to P. vivax erythrocytic infection. However, susceptibility to P. vivax in DARC+ individuals is reported to vary between specific DARC genotypes. We hypothesized that the natural acquisition of antibodies to P. vivax blood stages may vary with the host genotype and the level of DARC expression. Furthermore, high parasitemia has been reported to effect the acquisition of immunity against pre-erythrocytic parasites. We investigated the correlation between host DARC genotypes and the frequency and magnitude of antibodies against P. vivax erythrocytic stage antigens. Methodology/Findings We assessed the frequencies and magnitudes of antibody responses against P. vivax and P. falciparum sporozoite and erythrocytic antigens in Colombian donors from malaria-endemic regions. The frequency and level of naturally-acquired antibodies against the P. vivax erythrocytic antigens merozoite surface protein 1 (PvMSP1) and Duffy binding protein (PvDBP) varied with the host DARC genotypes. Donors with one negative allele (FY*B/FY*Bnull and FY*A/FY*Bnull) were more likely to have anti-PvMSP1 and anti-PvDBP antibodies than those with two positive alleles (FY*B/FY*B and FY*A/FY*B). The lower IgG3 and IgG1 components of the total IgG response may account for the decreased responses to P. vivax erythrocytic antigens with FY*A/FY*B and FY*B/FY*B genotypes. No such association was detected with P. falciparum erythrocytic antigens, which does not use DARC for erythrocyte invasion. Conclusion/Significance Individuals with higher DARC expression, which is associated with higher susceptibility to P. vivax infection, exhibited low frequencies and magnitudes of P. vivax blood-stage specific antibody responses. This may indicate that one of the

  2. Acquired antibody responses against Plasmodium vivax infection vary with host genotype for duffy antigen receptor for chemokines (DARC.

    Directory of Open Access Journals (Sweden)

    Amanda Maestre

    2010-07-01

    Full Text Available Polymorphism of the Duffy Antigen Receptor for Chemokines (DARC is associated with susceptibility to and the severity of Plasmodium vivax malaria in humans. P. vivax uses DARC to invade erythrocytes. Individuals lacking DARC are 'resistant' to P. vivax erythrocytic infection. However, susceptibility to P. vivax in DARC+ individuals is reported to vary between specific DARC genotypes. We hypothesized that the natural acquisition of antibodies to P. vivax blood stages may vary with the host genotype and the level of DARC expression. Furthermore, high parasitemia has been reported to effect the acquisition of immunity against pre-erythrocytic parasites. We investigated the correlation between host DARC genotypes and the frequency and magnitude of antibodies against P. vivax erythrocytic stage antigens.We assessed the frequencies and magnitudes of antibody responses against P. vivax and P. falciparum sporozoite and erythrocytic antigens in Colombian donors from malaria-endemic regions. The frequency and level of naturally-acquired antibodies against the P. vivax erythrocytic antigens merozoite surface protein 1 (PvMSP1 and Duffy binding protein (PvDBP varied with the host DARC genotypes. Donors with one negative allele (FY*B/FY*Bnull and FY*A/FY*Bnull were more likely to have anti-PvMSP1 and anti-PvDBP antibodies than those with two positive alleles (FY*B/FY*B and FY*A/FY*B. The lower IgG3 and IgG1 components of the total IgG response may account for the decreased responses to P. vivax erythrocytic antigens with FY*A/FY*B and FY*B/FY*B genotypes. No such association was detected with P. falciparum erythrocytic antigens, which does not use DARC for erythrocyte invasion.Individuals with higher DARC expression, which is associated with higher susceptibility to P. vivax infection, exhibited low frequencies and magnitudes of P. vivax blood-stage specific antibody responses. This may indicate that one of the primary mechanisms by which P. vivax evades

  3. Performance Characteristics of Different Anti-Double-Stranded DNA Antibody Assays in the Monitoring of Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Michael Mahler

    2017-01-01

    Full Text Available Objective. We sought to evaluate different anti-double-stranded DNA assays for their performance characteristics in monitoring disease activity fluctuations in systemic lupus erythematosus (SLE. Methods. 36 active SLE patients were followed monthly. At each study visit (total n=371, blood was collected and disease activity was scored using the SELENA-SLEDAI (excluding anti-dsDNA or complement components and by a physician’s global assessment (PGA. Four anti-dsDNA tests were compared. Linear mixed-effects models with random intercept and fixed slopes were used to evaluate the relationship between the longitudinal fluctuations of disease activity and anti-dsDNA titers. Results. At enrollment, positivity for QUANTA Lite and high-avidity anti-dsDNA assay was both 64% and significantly lower than anti-dsDNA positivity by QUANTA Flash (83% and CLIFT (96%. Linear mixed-effects modeling indicated that the change in clinical SELENA-SLEDAI scores was associated with the titers of all anti-dsDNA with QUANTA Flash yielding the highest marginal R2 (0.15; p<0.01. QUANTA Flash was the only anti-dsDNA assay significantly associated with the change in PGA (marginal R2=0.05; p<0.01. Conclusion. These data indicate that anti-dsDNA antibodies determined by QUANTA Flash have a value in monitoring SLE disease activity.

  4. Donor-derived HLA antibody production in patients undergoing SCT from HLA antibody-positive donors.

    Science.gov (United States)

    Taniguchi, K; Yoshihara, S; Maruya, E; Ikegame, K; Kaida, K; Hayashi, K; Kato, R; Inoue, T; Fujioka, T; Tamaki, H; Okada, M; Onuma, T; Fujii, N; Kusunoki, Y; Soma, T; Saji, H; Ogawa, H

    2012-10-01

    Pre-existing donor-specific HLA antibodies in patients undergoing HLA-mismatched SCT have increasingly been recognized as a risk factor for primary graft failure. However, the clinical implications of the presence of HLA antibodies in donors remain unknown. We prospectively examined 123 related donors for the presence of HLA antibodies by using a Luminex-based single antigen assay. Of these, 1/57 (1.8%) male, 6/27 (22%) parous female and 0/39 (0%) nonparous female donors were HLA antibody-positive. Then, we determined the presence of HLA antibodies in seven patients who received SCT from antibody-positive donors. Of these, four became HLA antibody-positive after SCT. The specificities of the antibodies that emerged in the patients closely resembled those of the antibodies found in the donors, indicating their production by donor-derived plasma cells. Moreover, the kinetics of the HLA antibody levels were similar in all four patients: levels started increasing within 1 week after SCT and peaked at days 10-21, followed by a gradual decrease. These results suggest that donor-derived HLA antibody production frequently occurs in patients undergoing SCT from antibody-positive donors. Further studies are warranted for clarifying the clinical significance of donor-derived HLA antibodies, including the role of these antibodies in post transplant platelet transfusion refractoriness.

  5. DARPA Antibody Technology Program. Standardized Test Bed for Antibody Characterization: Characterization of an MS2 ScFv Antibody Produced by Illumina

    Science.gov (United States)

    2016-08-01

    ECBC-TR-1395 DARPA ANTIBODY TECHNOLOGY PROGRAM STANDARDIZED TEST BED FOR... ANTIBODY CHARACTERIZATION: CHARACTERIZATION OF AN MS2 SCFV ANTIBODY PRODUCED BY ILLUMINA Patricia E. Buckley Alena M. Calm Heather Welsh Roy...4. TITLE AND SUBTITLE DARPA Antibody Technology Program Standardized Test Bed for Antibody Characterization: Characterization of an MS2 ScFv

  6. Antibody

    Science.gov (United States)

    ... AK, Litchman AH, Pillai S, eds. Cellular and Molecular Immunology . 8th ed. Philadelphia, PA: Elsevier Saunders; 2015:chap ... D, Brostoff J, Roth DB, Roitt IM, eds. Immunology . 8th ed. Philadelphia, PA: Elsevier Saunders; 2013:chap ...

  7. Monoclonal anti-melanoma antibodies and their possible clinical use

    International Nuclear Information System (INIS)

    Hellstroem, K.E.; Hellstroem, Ingegerd; Washington Univ., Seattle; Washington Univ., Seattle

    1985-01-01

    Cell surface antigens of human melanoma, as defined by monoclonal antibodies, are discussed and in particular the three antigens p97, a GD3 ganglioside and a proteoglycan. The potential diagnostic uses of antibodies to melanoma antigens are reviewed including in vitro diagnosis by immuno-histology, in vitro diagnosis by serum assays and in vivo diagnosis by tumour imaging using radioactively labelled antibodies. The potential therapeutic uses of monoclonal antibodies to melanoma antigens are also reviewed including targets for antibody therapy, the use of antibodies alone, radiolabelled antibodies, antibody-toxin conjugates, antibody-drug conjugates, anti-idiotypic antibodies and vaccines. (UK)

  8. Anticardiolipin antibodies in rheumatoid arthritis.

    Science.gov (United States)

    Keane, A; Woods, R; Dowding, V; Roden, D; Barry, C

    1987-10-01

    Anticardiolipin antibody (ACA) was present in the sera of 49% of 90 consecutive patients with rheumatoid arthritis (RA). The ACA was absent in 30 control patients with osteoarthritis. C-reactive protein levels equal to or exceeding 7 mg/dl were found in 10 patients all of whom were ACA positive. ACA was present in a larger proportion of rheumatoid factor (RF) positive than of RF negative patients. Male sex and extra-articular manifestations of RA were both more common in ACA positive than ACA negative patients. In the ACA positive group the lupus anticoagulant and VDRL tests were negative. However, a small number of patients had evidence of vascular events.

  9. Radiometallating antibodies and autoantigenic peptides

    International Nuclear Information System (INIS)

    Mercer-Smith, J.A.; Lewis, D.; Cole, D.A.; Newmyer, S.L.; Schulte, L.D.; Mixon, P.L.; Schreyer, S.A.; Burns, T.P.; Roberts, J.C.; Figard, S.D.; McCormick, D.J.; Lennon, V.A.; Hayashi, M.; Lavallee, D.K.

    1991-01-01

    We have developed methods to radiolabel large molecules, using porphyrins as bifunctional chelating agents for radiometals. The porphyrins are substituted with an N- benzyl group to activate them for radiometallation under mild reaction conditions. Porphyrins that have one functional group for covalent attachment to other molecules cannot cause crosslinking. We have examined the labeling chemistry for antibodies and have developed methods to label smaller biologically active molecules, such as autoantigenic peptides (fragments of the acetylcholine receptor), which are pertinent to myasthenia gravis research. The methods of covalent attachment of these bifunctional chelating agents to large molecules, the radiometallation chemistry, and biological characterization of the radiolabeled compounds will be discussed

  10. Update on antiphospholipid antibody syndrome.

    Science.gov (United States)

    Lopes, Michelle Remião Ugolini; Danowski, Adriana; Funke, Andreas; Rêgo, Jozelia; Levy, Roger; Andrade, Danieli Castro Oliveira de

    2017-11-01

    Antiphospholipid syndrome (APS) is an autoimmune disease characterized by antiphospholipid antibodies (aPL) associated with thrombosis and/or pregnancy morbidity. Most APS events are directly related to thrombotic events, which may affect small, medium or large vessels. Other clinical features like thrombocytopenia, nephropathy, cardiac valve disease, cognitive dysfunction and skin ulcers (called non-criteria manifestations) add significant morbidity to this syndrome and represent clinical situations that are challenging. APS was initially described in patients with systemic lupus erythematosus (SLE) but it can occur in patients without any other autoimmune disease. Despite the autoimmune nature of this syndrome, APS treatment is still based on anticoagulation and antiplatelet therapy.

  11. Preparation of antibody coated tubes

    International Nuclear Information System (INIS)

    Robles Berrueta, A.M.

    1997-01-01

    Full text: 1. Purification of IgG: 2-4 ml serum at pH 8 with Buffer tris 1M pH 8. Let serum pass through the column of Sepharose Prot. A (1-2 ml). Wash with: a) Buffer tris 0.1M pH 8; b) Buffer tris 0.01M pH 8. Elute with Glycine 0.1M pH 3 adding eluant at 0.5 ml fractions and collect in eppendorf tubes containing 50μ1 Buffer tris 1M pH 8 to neutralize. 20 fractions are collected. Absorbency at 280nm is measured in each fraction. Pool is formed with protein factions. Dialysis against water is done during 48 hours changing water twice during that lapse. Regenerate column for future use with 1 wash Urea 2M, second with LiCl 1M and third wash with Glycine 0.1 M pH 2.5. 2. Antibody Immobilization on an Activated Solid Phase: NUNC maxisorp, Star tube 75x12 mm is trade mark for polystyrene tubes from Pharmacia with less than 5% CV% inhomogeneity in adsorption of IgG and less than 10% for random bias of any result from mean value. They are kept closed until use. They are not reusable. The antibody is diluted to a working dilution with buffer carbonate-bi carbonate 0.1M, pH 9.6 (BCBic). Adequate volume is pipetted into maxisorb NUNC tubes paying attention not to produce droplets (1/200 dilution and 0.3 ml/tube are used for TSH assays). An incubation overnight is enough to get maximum IgG binding. Antibody solution is recovered for further use (after mixing with additional antibody). Solid phase is subject to washing with phosphate buffer with non-Ionic detergent (1 ml PB.5 + 0.5% Tween 20) and then with pure water. Tubes are left two hours upside down and kept tightly closed with dissicant at - 20 deg. C

  12. An MHC-restricted antibody-based chimeric antigen receptor requires TCR-like affinity to maintain antigen specificity

    Directory of Open Access Journals (Sweden)

    Marcela V Maus

    2016-01-01

    Full Text Available Chimeric antigen receptors (CARs are synthetic receptors that usually redirect T cells to surface antigens independent of human leukocyte antigen (HLA. Here, we investigated a T cell receptor-like CAR based on an antibody that recognizes HLA-A*0201 presenting a peptide epitope derived from the cancer-testis antigen NY-ESO-1. We hypothesized that this CAR would efficiently redirect transduced T cells in an HLA-restricted, antigen-specific manner. However, we found that despite the specificity of the soluble Fab, the same antibody in the form of a CAR caused moderate lysis of HLA-A2 expressing targets independent of antigen owing to T cell avidity. We hypothesized that lowering the affinity of the CAR for HLA-A2 would improve its specificity. We undertook a rational approach of mutating residues that, in the crystal structure, were predicted to stabilize binding to HLA-A2. We found that one mutation (DN lowered the affinity of the Fab to T cell receptor-range and restored the epitope specificity of the CAR. DN CAR T cells lysed native tumor targets in vitro, and, in a xenogeneic mouse model implanted with two human melanoma lines (A2+/NYESO+ and A2+/NYESO−, DN CAR T cells specifically migrated to, and delayed progression of, only the HLA-A2+/NY-ESO-1+ melanoma. Thus, although maintaining MHC-restricted antigen specificity required T cell receptor-like affinity that decreased potency, there is exciting potential for CARs to expand their repertoire to include a broad range of intracellular antigens.

  13. Production and characterization of peptide antibodies

    DEFF Research Database (Denmark)

    Trier, Nicole Hartwig; Hansen, Paul Robert; Houen, Gunnar

    2012-01-01

    Proteins are effective immunogens for generation of antibodies. However, occasionally the native protein is known but not available for antibody production. In such cases synthetic peptides derived from the native protein are good alternatives for antibody production. These peptide antibodies...... are powerful tools in experimental biology and are easily produced to any peptide of choice. A widely used approach for production of peptide antibodies is to immunize animals with a synthetic peptide coupled to a carrier protein. Very important is the selection of the synthetic peptide, where factors......, including solid-phase peptide-carrier conjugation and peptide-carrier conjugation in solution. Upon immunization, adjuvants such as Al(OH)(3) are added together with the immunogenic peptide-carrier conjugate, which usually leads to high-titred antisera. Following immunization and peptide antibody...

  14. Conference scene: progress with promising human antibodies.

    Science.gov (United States)

    Larrick, James W

    2012-03-01

    Antibodies and antibody-based therapeutics have become big business, with annual sales over US$50 billion, accounting for >6% of worldwide pharmaceutical revenues. Ten molecules have blockbuster status (>US$1 billion), with six generating more than US$6 billion in sales. In excess of 300 products based on this rapidly maturing technology are in clinical trials. The generation and manufacture of human antibodies is now routine, although the cost of goods remains an issue. Optimizing combinations of antibodies with other therapeutics (e.g., chemotherapy) is a major short-term goal, while target validation and product differentiation remain significant hurdles if growth is to continue. Some of the notable highlights of the recent 16th International Conference on Human Antibodies and Hybridomas meeting in Cannes, France are described below. The conference was sponsored by the international journal Human Antibodies, in association with the Integrative Medical Sciences Association (IMSA). The Program Chairman was Professor Mark Glassy, IMSA, San Diego, CA, USA.

  15. Production of Monoclonal Antibodies specific for Progesterone

    OpenAIRE

    YÜCEL, Fatıma

    2014-01-01

    Progesterone levels in milk and serum are indicators of pregnancy in cattle. The progesterone level reaches a peak on the 21 st and 22 nd days of pregnancy. Monoclonal antibodies specific to progesterone could be used for the immunodetection of milk and serum progesterone levels. We report here the development of hybrid cells prdoducing monoclonal antibodies specific for progesterone using hybridoma technology. Hybridoma cells secreting monoclonal antibodies against progesterone (MAM 2H1...

  16. [Ma2 antibody and multiple mononeuropathies].

    Science.gov (United States)

    Ayrignac, X; Castelnovo, G; Landrault, E; Fayolle, H; Pers, Y-M; Honnorat, J; Campello, C; Figarella-Branger, D; Labauge, P

    2008-01-01

    Anti-Ma2 antibodies belong to a family of onconeuronal antibodies that target proteins expressed in brain, testis and several tumors. Previously observed in patients presenting with limbic encephalitis, they seem to be associated with several other paraneoplastic syndromes. We report the case of a 73-year-old woman presenting sensory and motor neuropathy associated with non-small-cell lung cancer who had Ma2-antibodies.

  17. An anti vimentin antibody promotes tube formation

    DEFF Research Database (Denmark)

    Jørgensen, Mathias Lindh; Møller, Carina Kjeldahl; Rasmussen, Lasse

    2017-01-01

    antibody technology, promotes tube formation of endothelial cells in a 2D matrigel assay. By binding vimentin, the antibody increases the tube formation by 21% after 5 hours of incubation. Addition of the antibody directly to cultured endothelial cells does not influence endothelial cell migration...... or proliferation. The enhanced tube formation can be seen for up to 10 hours where after the effect decreases. It is shown that the antibody-binding site is located on the coil 2 domain of vimentin. To our knowledge this is the first study that demonstrates an enhanced tube formation by binding vimentin in a 2D...

  18. Antibodies against chromosomal beta-lactamase

    DEFF Research Database (Denmark)

    Giwercman, B; Rasmussen, J W; Ciofu, Oana

    1994-01-01

    A murine monoclonal anti-chromosomal beta-lactamase antibody was developed and an immunoblotting technique was used to study the presence of serum and sputum antibodies against Pseudomonas aeruginosa chromosomal group 1 beta-lactamase in patients with cystic fibrosis (CF). The serum antibody...... 1 cephalosporinase. We found a wide range of chromosomal beta-lactamase activity in the sputum samples, with no correlation with basal or induced activity of beta-lactamase expression. The presence of anti-beta-lactamase antibodies in endobronchial sputum could be an important factor in the defense...

  19. Uses of monoclonal antibody 8H9

    Energy Technology Data Exchange (ETDEWEB)

    Cheung, Nai-Kong V.

    2018-04-10

    This invention provides a composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a suitable carrier. This invention provides a pharmaceutical composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a pharmaceutically acceptable carrier. This invention also provides an antibody other than the monoclonal antibody 8H9 comprising the complementary determining regions of monoclonal antibody 8H9 or a derivative thereof, capable of binding to the same antigen as the monoclonal antibody 8H9. This invention provides a substance capable of competitively inhibiting the binding of monoclonal antibody 8H9. This invention also provides an isolated scFv of monoclonal antibody 8H9 or a derivative thereof. This invention also provides the 8H9 antigen. This invention also provides a method of inhibiting the growth of tumor cells comprising contacting said tumor cells with an appropriate amount of monoclonal antibody 8H9 or a derivative thereof.

  20. Exceptional Antibodies Produced by Successive Immunizations.

    Directory of Open Access Journals (Sweden)

    Patricia J Gearhart

    2015-12-01

    Full Text Available Antibodies stand between us and pathogens. Viruses mutate quickly to avoid detection, and antibodies mutate at similar rates to hunt them down. This death spiral is fueled by specialized proteins and error-prone polymerases that change DNA sequences. Here, we explore how B lymphocytes stay in the race by expressing activation-induced deaminase, which unleashes a tsunami of mutations in the immunoglobulin loci. This produces random DNA substitutions, followed by selection for the highest affinity antibodies. We may be able to manipulate the process to produce better antibodies by expanding the repertoire of specific B cells through successive vaccinations.

  1. Immune Antibody Libraries: Manipulating The Diverse Immune Repertoire for Antibody Discovery.

    Science.gov (United States)

    Lim, Theam Soon; Chan, Soo Khim

    2016-01-01

    Antibody phage display is highly dependent on the availability of antibody libraries. There are several forms of libraries depending mainly on the origin of the source materials. There are three major classes of libraries, mainly the naïve, immune and synthetic libraries. Immune antibody libraries are designed to isolate specific and high affinity antibodies against disease antigens. The pre-exposure of the host to an infection results in the production of a skewed population of antibodies against the particular infection. This characteristic takes advantage of the in vivo editing machinery to generate bias and specific immune repertoire. The skewed but diverse repertoire of immune libraries has been adapted successfully in the generation of antibodies against a wide range of diseases. We envisage immune antibody libraries to play a greater role in the discovery of antibodies for diseases in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Differential lymphocyte and antibody responses in deer mice infected with Sin Nombre hantavirus or Andes hantavirus.

    Science.gov (United States)

    Schountz, Tony; Quackenbush, Sandra; Rovnak, Joel; Haddock, Elaine; Black, William C; Feldmann, Heinz; Prescott, Joseph

    2014-08-01

    Hantavirus cardiopulmonary syndrome (HCPS) is a rodent-borne disease with a high case-fatality rate that is caused by several New World hantaviruses. Each pathogenic hantavirus is naturally hosted by a principal rodent species without conspicuous disease and infection is persistent, perhaps for life. Deer mice (Peromyscus maniculatus) are the natural reservoirs of Sin Nombre virus (SNV), the etiologic agent of most HCPS cases in North America. Deer mice remain infected despite a helper T cell response that leads to high-titer neutralizing antibodies. Deer mice are also susceptible to Andes hantavirus (ANDV), which causes most HCPS cases in South America; however, deer mice clear ANDV. We infected deer mice with SNV or ANDV to identify differences in host responses that might account for this differential outcome. SNV RNA levels were higher in the lungs but not different in the heart, spleen, or kidneys. Most ANDV-infected deer mice had seroconverted 14 days after inoculation, but none of the SNV-infected deer mice had. Examination of lymph node cell antigen recall responses identified elevated immune gene expression in deer mice infected with ANDV and suggested maturation toward a Th2 or T follicular helper phenotype in some ANDV-infected deer mice, including activation of the interleukin 4 (IL-4) pathway in T cells and B cells. These data suggest that the rate of maturation of the immune response is substantially higher and of greater magnitude during ANDV infection, and these differences may account for clearance of ANDV and persistence of SNV. Hantaviruses persistently infect their reservoir rodent hosts without pathology. It is unknown how these viruses evade sterilizing immune responses in the reservoirs. We have determined that infection of the deer mouse with its homologous hantavirus, Sin Nombre virus, results in low levels of immune gene expression in antigen-stimulated lymph node cells and a poor antibody response. However, infection of deer mice with a

  3. An efficient method for isolating antibody fragments against small peptides by antibody phage display

    DEFF Research Database (Denmark)

    Duan, Zhi; Siegumfeldt, Henrik

    2010-01-01

    We generated monoclonal scFv (single chain variable fragment) antibodies from an antibody phage display library towards three small synthetic peptides derived from the sequence of s1-casein. Key difficulties for selection of scFv-phages against small peptides were addressed. Small peptides do....... The scFvs were sequenced and characterized, and specificity was characterized by ELISA. The methods developed in this study are universally applicable for antibody phage display to efficiently produce antibody fragments against small peptides....

  4. Stratification of Antibody-Positive Subjects by Antibody Level Reveals an Impact of Immunogenicity on Pharmacokinetics

    OpenAIRE

    Zhou, Lei; Hoofring, Sarah A.; Wu, Yu; Vu, Thuy; Ma, Peiming; Swanson, Steven J.; Chirmule, Narendra; Starcevic, Marta

    2012-01-01

    The availability of highly sensitive immunoassays enables the detection of antidrug antibody (ADA) responses of various concentrations and affinities. The analysis of the impact of antibody status on drug pharmacokinetics (PK) is confounded by the presence of low-affinity or low-concentration antibody responses within the dataset. In a phase 2 clinical trial, a large proportion of subjects (45%) developed ADA following weekly dosing with AMG 317, a fully human monoclonal antibody therapeutic....

  5. Anti-idiotypic antibodies to poliovirus antibodies in commercial immunoglubulin preparations, human serum and milk.

    NARCIS (Netherlands)

    M. Hahn-Zoric; B. Carlsson; S. Jeansson; H.P. Ekre; A.D.M.E. Osterhaus (Albert); D. Roberton; L.A. Hanson

    1993-01-01

    textabstractOur previous studies have suggested that fetal antibody production can be induced by maternal antiidiotypic antibodies transferred to the fetus via the placenta. We tested commercial Ig, sera, and milk for the presence of anti-idiotypic antibodies to poliovirus type 1, using affinity

  6. Antibody or Antibody Fragments : Implications for Molecular Imaging and Targeted Therapy of Solid Tumors

    NARCIS (Netherlands)

    Xenaki, Katerina T; Oliveira, Sabrina; van Bergen En Henegouwen, Paul M P

    2017-01-01

    The use of antibody-based therapeutics has proven very promising for clinical applications in cancer patients, with multiple examples of antibodies and antibody-drug conjugates successfully applied for the treatment of solid tumors and lymphomas. Given reported recurrence rates, improvements are

  7. The production of antibody fragments and antibody fusion proteins by yeasts and filamentous fungi

    NARCIS (Netherlands)

    Joosten, V.; Lokman, C.; Hondel, C.A.M.J.J. van den; Punt, P.J.

    2003-01-01

    In this review we will focus on the current status and views concerning the production of antibody fragments and antibody fusion proteins by yeasts and filamentous fungi. We will focus on single-chain antibody fragment production (scFv and VHH) by these lower eukaryotes and the possible applications

  8. Antibody Characterization Process | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The goal of the NCI's Antibody Characterization Program (ACP) is to have three monoclonal antibodies produced for each successfully expressed/purified recombinant antigen and one antibody per peptide (1 to 3 peptides per protein). To date, over 4000 clones have been screened before selecting the current 393 antibodies. They are winnowed down based on the projected end use of the antibody.

  9. 21 CFR 866.3290 - Gonococcal antibody test (GAT).

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Gonococcal antibody test (GAT). 866.3290 Section... antibody test (GAT). (a) Identification. A gonococcal antibody test (GAT) is an in vitro device that..., indirect fluorescent antibody, or radioimmunoassay, antibodies to Neisseria gonorrhoeae in sera of...

  10. Monoclonal antibodies in pediatric allergy

    Directory of Open Access Journals (Sweden)

    Amelia Licari

    2015-10-01

    Full Text Available Production of monoclonal antibodies (mAbs involving human-mouse hybrid cells was first described in 1970s, but these biologics are now used for a variety of diseases including cancers, autoimmune disorders and allergic diseases. The aim of this article is to review current and future applications of mAbs, in particular focusing on anti-IgE therapy, in the field of pediatric allergy. Proceedings of the 11th International Workshop on Neonatology and Satellite Meetings · Cagliari (Italy · October 26th-31st, 2015 · From the womb to the adultGuest Editors: Vassilios Fanos (Cagliari, Italy, Michele Mussap (Genoa, Italy, Antonio Del Vecchio (Bari, Italy, Bo Sun (Shanghai, China, Dorret I. Boomsma (Amsterdam, the Netherlands, Gavino Faa (Cagliari, Italy, Antonio Giordano (Philadelphia, USA

  11. Applications of recombinant antibodies in plant pathology.

    Science.gov (United States)

    Ziegler, Angelika; Torrance, Lesley

    2002-09-01

    Summary Advances in molecular biology have made it possible to produce antibody fragments comprising the binding domains of antibody molecules in diverse heterologous systems, such as Escherichia coli, insect cells, or plants. Antibody fragments specific for a wide range of antigens, including plant pathogens, have been obtained by cloning V-genes from lymphoid tissue, or by selection from large naive phage display libraries, thus avoiding the need for immunization. The antibody fragments have been expressed as fusion proteins to create different functional molecules, and fully recombinant assays have been devised to detect plant viruses. The defined binding properties and unlimited cheap supply of antibody fusion proteins make them useful components of standardized immunoassays. The expression of antibody fragments in plants was shown to confer resistance to several plant pathogens. However, the antibodies usually only slowed the progress of infection and durable 'plantibody' resistance has yet to be demonstrated. In future, it is anticipated that antibody fragments from large libraries will be essential tools in high-throughput approaches to post-genomics research, such as the assignment of gene function, characterization of spatio-temporal patterns of protein expression, and elucidation of protein-protein interactions.

  12. Monoclonal antibodies reactive with hairy cell leukemia

    NARCIS (Netherlands)

    Visser, L; Shaw, A; Slupsky, J; Vos, H; Poppema, S

    Monoclonal antibodies reactive with hairy cell leukemia were developed to aid in the diagnosis of this subtype of B cell chronic lymphocytic leukemia and to gain better insight into the origin of hairy cells. Three antibodies were found to be of value in the diagnosis of hairy cell leukemia.

  13. Photonic crystal fiber based antibody detection

    DEFF Research Database (Denmark)

    Duval, A; Lhoutellier, M; Jensen, J B

    2004-01-01

    An original approach for detecting labeled antibodies based on strong penetration photonic crystal fibers is introduced. The target antibody is immobilized inside the air-holes of a photonic crystal fiber and the detection is realized by the means of evanescent-wave fluorescence spectroscopy...

  14. Antibody therapies for lymphoma in children

    NARCIS (Netherlands)

    de Zwart, Verena; Gouw, Samantha C.; Meyer-Wentrup, Friederike A. G.

    2016-01-01

    Lymphomas are the third most common malignancy in childhood. Cure rates are high but have reached a plateau. Therefore new treatment modalities should be developed. Antibody therapy is a successful new treatment option in adult lymphoma. However, none of the therapeutic antibodies available for

  15. Immunoscintigraphy of metastases with radiolabelled human antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Al-Azzawi, F.; Smith, J.; Stimson, W.H.

    1987-02-28

    It was concluded that Epstein-Barr virus transformation of committed lymphocytes offers great potential in the production of antitumour antibodies of human origin. An outline case report is presented where the human I/sup 131/ labelled antibody was used as a targeting agent to delineate the extent of secondary growth in the liver. (U.K.).

  16. Nanobodies - the new concept in antibody engineering

    African Journals Online (AJOL)

    STORAGESEVER

    2009-06-17

    Jun 17, 2009 ... These heavy-chain antibodies contain a single variable domain (VHH) and two ... clonal antibody products were on the market and more than 100 in ..... genous showing no sign of spontaneous dimerisation in contrast to scFv ...

  17. Monoclonal Antibody Therapy for Advanced Neuroblastoma

    Science.gov (United States)

    NCI is sponsoring two clinical trials of a monoclonal antibody called ch14.18, in combination with other drugs, to see if the antibody may be helpful for children or young adults (up to age 21) with relapsed or refractory neuroblastoma.

  18. Anti-influenza M2e antibody

    Science.gov (United States)

    Bradbury, Andrew M [Santa Fe, NM

    2011-12-20

    Humanized recombinant and monoclonal antibodies specific for the ectodomain of the influenza virus M2 ion channel protein are disclosed. The antibodies of the invention have anti-viral activity and may be useful as anti-viral therapeutics and/or prophylactic/vaccine agents for inhibiting influenza virus replication and for treating individuals infected with influenza.

  19. Anti‑livin antibodies in Hashimoto thyroiditis.

    Science.gov (United States)

    Baumann-Antczak, Aleksandra; Kosowicz, Jerzy; Zamysłowska, Hanna; Ruchała, Marek

    2012-01-01

    Livin belongs to the family of apoptosis inhibitors. High livin expression is observed in malignancies of the gastrointestinal tract, lungs, breast, and kidneys, but it is not present in differentiated adult tissues. In some malignant processes, anti‑livin antibodies are present. The aim of the study was to evaluate the prevalence of anti‑livin antibodies in Hashimoto thyroiditis, a disease characterized by rapid and widespread thyrocyte apoptosis. The study comprised 65 women with Hashimoto thyroiditis and the control group of 40 healthy women. In the majority of the patients, clinical manifestations of hypothyroidism were observed; all patients had high levels of serum antithyroid peroxidase antibodies. A solid‑phase radioimmunoassay in livin‑coated polyethylene tubes using 125I-labeled protein A was used to determine anti-livin antibodies. Significant amounts of anti-livin antibodies were reported in 18 patients (26.8%); 3 patients (4.6%) had borderline antibody levels; while in controls only 1 patient was positive (2.5%, P Hashimoto thyroiditis, an autoimmune process is more general and involves numerous autoantibodies including an antibody against apoptosis inhibitor - livin. Anti‑livin antibodies cannot serve only as a marker of malignancy because they are also present in autoimmune processes.

  20. A novel polyclonal antibody against human cytomegalovirus ...

    African Journals Online (AJOL)

    Future research should be directed to epitope screening of synthetic HMCV peptides, which could help to understand HCMV infection and virus-neutralising antibodies more fully and to prepare HCMV vaccines and antiviral drugs. Key words: Human cytomegalovirus, AD169 strain, Towne strains, polyclonal antibody.

  1. Nano antibody therapy for cancer

    International Nuclear Information System (INIS)

    Venkatachallam, M.; Sivakumar, T.; Nazeema; Venkateswari, P.

    2011-01-01

    Nanomedicine, an offshoot of nanotechnology, refers to highly specific medical intervention at the molecular scale for curing disease or repairing damaged tissues, such as bone, muscle, or nerve. Nanotechnology can have an early, paradigm-changing impact on how clinicians will detect cancer in its earliest stages. Exquisitely sensitive devices constructed of nanoscale components-such as nanocantilevers, nanowires and nanochannels-offer the potential for detecting even the rarest molecular signals associated with malignancy. One of the most pressing needs in clinical oncology is for imaging agents that can identify tumors that are far smaller than is possible with today's technology, at a scale of 100,000 cells rather than 1,000,000,000 cells. A new approach in nanotechnology for treating cancer incorporates nano iron particles and attaches them to an antibody that has targets only cancer cells and not healthy cells. The treatment works in two steps. This treatment is an ingenious way to make localized tumor ablation a systemic treatment. The advantages are incredible. There are absolutely no side effects from this treatment. It is not painful or even uncomfortable. The iron particles get flushed harmlessly from the body. It is not a drug and so the cancer cannot build up a resistance to the treatment. It is a systematic treatment; even cancer cells and tumors that are not known about get heated up and ablated. This treatment can even be used to enhance imaging of the cancer because once the cancer cells are coated with the iron particles, they are easy to identify. Everything depends on how reliably the antibodies target cancer cells and not healthy cells. When used in conjunction with other systemic treatments, such as vaccine treatments, we could be looking at a time when even advanced cancers can be brought under control. (author)

  2. Mean Recency Period for Estimation of HIV-1 Incidence with the BED-Capture EIA and Bio-Rad Avidity in Persons Diagnosed in the United States with Subtype B.

    Directory of Open Access Journals (Sweden)

    Debra L Hanson

    Full Text Available HIV incidence estimates are used to monitor HIV-1 infection in the United States. Use of laboratory biomarkers that distinguish recent from longstanding infection to quantify HIV incidence rely on having accurate knowledge of the average time that individuals spend in a transient state of recent infection between seroconversion and reaching a specified biomarker cutoff value. This paper describes five estimation procedures from two general statistical approaches, a survival time approach and an approach that fits binomial models of the probability of being classified as recently infected, as a function of time since seroconversion. We compare these procedures for estimating the mean duration of recent infection (MDRI for two biomarkers used by the U.S. National HIV Surveillance System for determination of HIV incidence, the Aware BED EIA HIV-1 incidence test (BED and the avidity-based, modified Bio-Rad HIV-1/HIV-2 plus O ELISA (BRAI assay. Collectively, 953 specimens from 220 HIV-1 subtype B seroconverters, taken from 5 cohorts, were tested with a biomarker assay. Estimates of MDRI using the non-parametric survival approach were 198.4 days (SD 13.0 for BED and 239.6 days (SD 13.9 for BRAI using cutoff values of 0.8 normalized optical density and 30%, respectively. The probability of remaining in the recent state as a function of time since seroconversion, based upon this revised statistical approach, can be applied in the calculation of annual incidence in the United States.

  3. Mean Recency Period for Estimation of HIV-1 Incidence with the BED-Capture EIA and Bio-Rad Avidity in Persons Diagnosed in the United States with Subtype B.

    Science.gov (United States)

    Hanson, Debra L; Song, Ruiguang; Masciotra, Silvina; Hernandez, Angela; Dobbs, Trudy L; Parekh, Bharat S; Owen, S Michele; Green, Timothy A

    2016-01-01

    HIV incidence estimates are used to monitor HIV-1 infection in the United States. Use of laboratory biomarkers that distinguish recent from longstanding infection to quantify HIV incidence rely on having accurate knowledge of the average time that individuals spend in a transient state of recent infection between seroconversion and reaching a specified biomarker cutoff value. This paper describes five estimation procedures from two general statistical approaches, a survival time approach and an approach that fits binomial models of the probability of being classified as recently infected, as a function of time since seroconversion. We compare these procedures for estimating the mean duration of recent infection (MDRI) for two biomarkers used by the U.S. National HIV Surveillance System for determination of HIV incidence, the Aware BED EIA HIV-1 incidence test (BED) and the avidity-based, modified Bio-Rad HIV-1/HIV-2 plus O ELISA (BRAI) assay. Collectively, 953 specimens from 220 HIV-1 subtype B seroconverters, taken from 5 cohorts, were tested with a biomarker assay. Estimates of MDRI using the non-parametric survival approach were 198.4 days (SD 13.0) for BED and 239.6 days (SD 13.9) for BRAI using cutoff values of 0.8 normalized optical density and 30%, respectively. The probability of remaining in the recent state as a function of time since seroconversion, based upon this revised statistical approach, can be applied in the calculation of annual incidence in the United States.

  4. Antiphospholipid antibody: laboratory, pathogenesis and clinical manifestations

    Directory of Open Access Journals (Sweden)

    T. Ziglioli

    2011-06-01

    Full Text Available Antiphospholipid antibodies (aPL represent a heterogeneous group of antibodies that recognize various antigenic targets including beta2 glycoprotein I (β2GPI, prothrombin (PT, activated protein C, tissue plasminogen activator, plasmin and annexin A2. The most commonly used tests to detect aPL are: lupus anticoagulant (LAC, a functional coagulation assay, anticardiolipin antibody (aCL and anti-β2GPI antibody (anti-β2GPI, which are enzyme-linked immunoassay (ELISA. Clinically aPL are associated with thrombosis and/or with pregnancy morbidity. Apparently aPL alone are unable to induce thrombotic manifestations, but they increase the risk of vascular events that can occur in the presence of another thrombophilic condition; on the other hand obstetrical manifestations were shown to be associated not only to thrombosis but mainly to a direct antibody effect on the trophoblast.

  5. Preparation of 188Re labelled antibodies

    International Nuclear Information System (INIS)

    Zhu Minghua; Cao Rongzhen; Li Wenxin; Sheng Rong; Yin Duanzhi; He Weiyu; Zhou Wei; Wang Yongxian

    1998-01-01

    A simple technique of directly labelling antibodies with 188 Re has been developed. The reduction of antibody disulfide groups was achieved by incubation of antibody with ascorbic acid (pH = 6.5) for an hour at room temperature and a solution of excess SnCl 2 in sodium gluconate was added to the AA-reduced antibody followed by the addition of perrhenate. Some factors that influence labelling efficiency, such as the pH of the reaction mixture, the labelling time, and the amount of antibodies and reductive agent, were studied experimentally and a better labelling method was established. The labelling yields, as determined by paper chromatography, were greater than 80%

  6. Taking aim at cancer with monoclonal antibodies

    International Nuclear Information System (INIS)

    Klausner, A.

    1986-01-01

    Conjugating radioisotopes to monoclonal antibodies could have certain advantages in cancer therapy. Radioactive compounds have the double-edged ability to kill cells that are up to centimeter or more away. This is a plausible way to overcome tumor heterogeneity, but it also means that normal cells near the tumor could be affected. Hybritech (San Diego, CA) has been supplying antibody linked to the radioisotope yttrium-90 for a number of clinical trials. Work at Johns Hopkins University (Baltimore, MD) has focused on polyclonal antibodies to hepatoma. Monoclonal antibodies will be used there soon, and trials could be expanded eventually to include breast, lung, and prostate cancer as well. Hybritech also expects that the yttrium-antibody conjugates developed with NCI will enter the clinic later this year for treating leukemia and lymphoma systems; treatments for melanomas should follow

  7. Immobilization of antibodies and enzyme-labeled antibodies by radiation polymerization

    International Nuclear Information System (INIS)

    Kumakura, M.; Kaetsu, I.; Suzuki, M.; Adachi, S.

    1983-01-01

    Immobilization of antibodies and enzyme-labeled antibodies by radiation polymerization at low temperatures was studied. The antibody activity of antibody was not affected by irradiation at an irradiation dose of below 8 MR and low temperatures. Immobilization of peroxidase-labeled anti-rabbit IgG goat IgG, anti-peroxidase, peroxidase, and anti-alpha-fetoprotein was carried out with hydrophilic and hydrophobic monomers. The activity of the immobilized enzyme-labeled antibody membranes varied with the thickness of the membranes and increased with decreasing membrane thickness. The activity of the immobilized antibody particles was varied by particle size. Immobilized anti-alpha-fetoprotein particles and membranes can be used for the assay of alpha-fetoprotein by the antigen-antibody reaction, such as a solid-phase sandwich method with high sensitivity

  8. Monoclonal antibody form and function: manufacturing the right antibodies for treating drug abuse.

    Science.gov (United States)

    Peterson, Eric; Owens, S Michael; Henry, Ralph L

    2006-05-26

    Drug abuse continues to be a major national and worldwide problem, and effective treatment strategies are badly needed. Antibodies are promising therapies for the treatment of medical problems caused by drug abuse, with several candidates in preclinical and early clinical trials. Monoclonal antibodies can be designed that have customized affinity and specificity against drugs of abuse, and because antibodies can be designed in various forms, in vivo pharmacokinetic characteristics can be tailored to suit specific clinical applications (eg, long-acting for relapse prevention, or short-acting for overdose). Passive immunization with antibodies against drugs of abuse has several advantages over active immunization, but because large doses of monoclonal antibodies may be needed for each patient, efficient antibody production technology is essential. In this minireview we discuss some of the antibody forms that may be effective clinical treatments for drug abuse, as well as several current and emerging production systems that could bridge the gap from discovery to patient use.

  9. Docking of Antibodies into Cavities in DNA Origami

    DEFF Research Database (Denmark)

    Quyang, X; Stefano, Mattia De; Krissanaprasit, Abhichart

    2017-01-01

    microscopy (AFM) and transmission electron microscopy (TEM) validated efficient antibody immobilization in the origami structures. The increased ability to control the orientation of antibodies in nanostructures and at surfaces has potential for directing the interactions of antibodies with targets...

  10. how to evade the immune system?

    Indian Academy of Sciences (India)

    HCV usually induces robust immune responses, but it frequently escapes the immune defense to establish persistent infection. The fact that HCV exists as an evolving quasispecies plays an important role in the selection of escape mutants. Furthermore, several viral proteins interfere with cellular functions, in particular, ...

  11. Maipäevad Dessaus / Maimu Berg

    Index Scriptorium Estoniae

    Berg, Maimu, 1945-

    1989-01-01

    Moekunstnike loomingulisest seminarist, mida juhendas professor ja vabakutseline kunstnik Bodo Müller, Dessaus Bauhausi hoones (Tallinnast osalesid Maimu Berg ja kunstnik Kristel Leedjärv); Bauhausi ajaloost

  12. Tallinna Merepäevade turismikonverents

    Index Scriptorium Estoniae

    2012-01-01

    13. juulil Lennusadama angaarides toimunud turismikonverentsist "Lennukad ideed Lennusadamas", kus esinesid Tallinna abilinnapea Taavi Aas, Tallinna Sadama ärisuunajuht Ahto Ader, müügijuht Aare Maurer, EHTE arenduse ja uuringute osakonna juhataja Ain Hinsberg, kes rääkis projektist "Cultural Tourism 2011", Tallinna Lennujaama juhatuse esimees Rein Loik, Lennusadama tegevjuht Ott Sarapuu

  13. Hullud päevad von Krahlis

    Index Scriptorium Estoniae

    2006-01-01

    Von Krahli Teatris mängitakse neil päevi neli korda Peeter Jalaka lavastuses Tõnu Kõrvitsa kammeroopereid "Tuliaed" ja "Mu luiged, mu mõtted", mille aluseks on luuletaja Marie Heibergi saatus. Libreto autor on Maarja Kangro. Kammerooperid tulevad lavale Von Krahli Teatri ja Nargen Opera koostöös. Esitavad Kädy Plaas, Helen Lokuta, Nargen Opera koor ja Tallinna Kammerorkester, dirigent Tõnu Kaljuste

  14. Baculovirus display of functional antibody Fab fragments.

    Science.gov (United States)

    Takada, Shinya; Ogawa, Takafumi; Matsui, Kazusa; Suzuki, Tasuku; Katsuda, Tomohisa; Yamaji, Hideki

    2015-08-01

    The generation of a recombinant baculovirus that displays antibody Fab fragments on the surface was investigated. A recombinant baculovirus was engineered so that the heavy chain (Hc; Fd fragment) of a mouse Fab fragment was expressed as a fusion to the N-terminus of baculovirus gp64, while the light chain of the Fab fragment was simultaneously expressed as a secretory protein. Following infection of Sf9 insect cells with the recombinant baculovirus, the culture supernatant was analyzed by enzyme-linked immunosorbent assay using antigen-coated microplates and either an anti-mouse IgG or an anti-gp64 antibody. A relatively strong signal was obtained in each case, showing antigen-binding activity in the culture supernatant. In western blot analysis of the culture supernatant using the anti-gp64 antibody, specific protein bands were detected at an electrophoretic mobility that coincided with the molecular weight of the Hc-gp64 fusion protein as well as that of gp64. Flow cytometry using a fluorescein isothiocyanate-conjugated antibody specific to mouse IgG successfully detected the Fab fragments on the surface of the Sf9 cells. These results suggest that immunologically functional antibody Fab fragments can be displayed on the surface of baculovirus particles, and that a fluorescence-activated cell sorter with a fluorescence-labeled antigen can isolate baculoviruses displaying specific Fab fragments. This successful baculovirus display of antibody Fab fragments may offer a novel approach for the efficient selection of specific antibodies.

  15. Glycosylation profiles of therapeutic antibody pharmaceuticals.

    Science.gov (United States)

    Wacker, Christoph; Berger, Christoph N; Girard, Philippe; Meier, Roger

    2011-11-01

    Recombinant antibodies specific for human targets are often used as therapeutics and represent a major class of drug products. Their therapeutic efficacy depends on the formation of antibody complexes resulting in the elimination of a target molecule or the modulation of specific signalling pathways. The physiological effects of antibody therapeutics are known to depend on the structural characteristics of the antibody molecule, specifically on the glycosylation which is the result of posttranslational modifications. Hence, production of therapeutic antibodies with a defined and consistent glycoform profile is needed which still remains a considerable challenge to the biopharmaceutical industry. To provide an insight into the industries capability to control their manufacturing process and to provide antibodies of highest quality, we conducted a market surveillance study and compared major oligosaccharide profiles of a number of monoclonal antibody pharmaceuticals sampled on the Swiss market. Product lot-to-lot variability was found to be generally low, suggesting that a majority of manufacturers have implemented high quality standards in their production processes. However, proportions of G0, G1 and G2 core-fucosylated chains derived from different products varied considerably and showed a bias towards the immature agalactosidated G0 form. Interestingly, differences in glycosylation caused by the production cell type seem to be of less importance compared with process related parameters such as cell growth. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Antibody proteases: induction of catalytic response.

    Science.gov (United States)

    Gabibov, A G; Friboulet, A; Thomas, D; Demin, A V; Ponomarenko, N A; Vorobiev, I I; Pillet, D; Paon, M; Alexandrova, E S; Telegin, G B; Reshetnyak, A V; Grigorieva, O V; Gnuchev, N V; Malishkin, K A; Genkin, D D

    2002-10-01

    Most of the data accumulated throughout the years on investigation of catalytic antibodies indicate that their production increases on the background of autoimmune abnormalities. The different approaches to induction of catalytic response toward recombinant gp120 HIV-1 surface protein in mice with various autoimmune pathologies are described. The peptidylphosphonate conjugate containing structural part of gp120 molecule is used for reactive immunization of NZB/NZW F1, MRL, and SJL mice. The specific modification of heavy and light chains of mouse autoantibodies with Val-Ala-Glu-Glu-Glu-Val-PO(OPh)2 reactive peptide was demonstrated. Increased proteolytic activity of polyclonal antibodies in SJL mice encouraged us to investigate the production of antigen-specific catalytic antibodies on the background of induced experimental autoimmune encephalomyelitis (EAE). The immunization of autoimmune-prone mice with the engineered fusions containing the fragments of gp120 and encephalitogenic epitope of myelin basic protein (MBP(89-104)) was made. The proteolytic activity of polyclonal antibodies isolated from the sera of autoimmune mice immunized by the described antigen was shown. Specific immune response of SJL mice to these antigens was characterized. Polyclonal antibodies purified from sera of the immunized animals revealed proteolytic activity. The antiidiotypic approach to raise the specific proteolytic antibody as an "internal image" of protease is described. The "second order" monoclonal antibodies toward subtilisin Carlsberg revealed pronounced proteolytic activity.

  17. HIV antibodies for treatment of HIV infection.

    Science.gov (United States)

    Margolis, David M; Koup, Richard A; Ferrari, Guido

    2017-01-01

    The bar is high to improve on current combination antiretroviral therapy (ART), now highly effective, safe, and simple. However, antibodies that bind the HIV envelope are able to uniquely target the virus as it seeks to enter new target cells, or as it is expressed from previously infected cells. Furthermore, the use of antibodies against HIV as a therapeutic may offer advantages. Antibodies can have long half-lives, and are being considered as partners for long-acting antiretrovirals for use in therapy or prevention of HIV infection. Early studies in animal models and in clinical trials suggest that such antibodies can have antiviral activity but, as with small-molecule antiretrovirals, the issues of viral escape and resistance will have to be addressed. Most promising, however, are the unique properties of anti-HIV antibodies: the potential ability to opsonize viral particles, to direct antibody-dependent cellular cytotoxicity (ADCC) against actively infected cells, and ultimately the ability to direct the clearance of HIV-infected cells by effector cells of the immune system. These distinctive activities suggest that HIV antibodies and their derivatives may play an important role in the next frontier of HIV therapeutics, the effort to develop treatments that could lead to an HIV cure. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  18. Stratification of antibody-positive subjects by antibody level reveals an impact of immunogenicity on pharmacokinetics.

    Science.gov (United States)

    Zhou, Lei; Hoofring, Sarah A; Wu, Yu; Vu, Thuy; Ma, Peiming; Swanson, Steven J; Chirmule, Narendra; Starcevic, Marta

    2013-01-01

    The availability of highly sensitive immunoassays enables the detection of antidrug antibody (ADA) responses of various concentrations and affinities. The analysis of the impact of antibody status on drug pharmacokinetics (PK) is confounded by the presence of low-affinity or low-concentration antibody responses within the dataset. In a phase 2 clinical trial, a large proportion of subjects (45%) developed ADA following weekly dosing with AMG 317, a fully human monoclonal antibody therapeutic. The antibody responses displayed a wide range of relative concentrations (30 ng/mL to >13 μg/mL) and peaked at various times during the study. To evaluate the impact of immunogenicity on PK, AMG 317 concentration data were analyzed following stratification by dose group, time point, antibody status (positive or negative), and antibody level (relative concentration). With dose group as a stratifying variable, a moderate reduction in AMG 317 levels (AMG 317 levels was revealed when antibody data was stratified by both time point and antibody level. In general, high ADA concentrations (>500 ng/mL) and later time points (week 12) were associated with significantly (up to 97%) lower trough AMG 317 concentrations. The use of quasi-quantitative antibody data and appropriate statistical methods was critical for the most comprehensive evaluation of the impact of immunogenicity on PK.

  19. Effect of antibody charge and concentration on deposition of antibody to glomerular basement membrane

    International Nuclear Information System (INIS)

    Madaio, M.P.; Salant, D.J.; Adler, S.; Darby, C.; Couser, W.G.

    1984-01-01

    Fixed anionic sites within the glomerular capillary wall influence the permeation of serum proteins, the localization of various antigens, and the deposition of antibody in the subepithelial space. In anti-GBM nephritis antibody deposition occurs very rapidly to antigenic sites located relatively proximal in the glomerular capillary wall. The authors examined the influence of the glomerular charge barrier on anti-GBM antibody deposition by comparing the rate of deposition of antibodies with cationic and anionic isoelectric points. Purified sheep anti-rat GBM IgG was isolated from acid eluates of kidneys obtained 24 hr after rats were injected with sheep antiserum to rat GBM. Anti-GBM IgG was separated into cationic (pI 6.4-8.5) and anionic (pI 4.2-6.8) fractions, which were radiolabelled with 131 I and 125 I, respectively, shown to have equal antibody contents measured by in vitro binding to normal glomeruli, mixed in equal amounts, and injected in incremental doses to ten rats. At 1 hr the glomerular antibody binding of each fraction was directly related to the blood level (r . 0.95, r . 0.97) and delivery of antibody (r . 0.98, r . 0.98). Glomerular binding of cationic antibody was four times greater than anionic antibody over the entire range of deliveries studied (P less than 0.001). The authors conclude that glomerular deposition of anti-GBM antibody is directly related to blood concentration and delivery of antibody. Furthermore, the deposition of cationic antibodies to GBM antigens was significantly greater than the deposition of anionic antibodies

  20. Uses of monoclonial antibody 8H9

    Science.gov (United States)

    Cheung, Nai-Kong V.

    2015-06-23

    This invention provides an antibody that binds the same antigen as that of monoclonal antibody 8H9, wherein the heavy chain CDR (Complementary Determining Region)1 comprises NYDIN, heavy chain CDR2 comprises WIFPGDGSTQY, heavy chain CDR3 comprises QTTATWFAY, and the light chain CDR1 comprises RASQSISDYLH, light chain CDR2 comprises YASQSIS, and light chain CDR3 comprises QNGHSFPLT. In another embodiment, there is provided a polypeptide that binds the same antigen as that of monoclonal antibody 8H9, wherein the polypeptide comprises NYDIN, WIFPGDGSTQY, QTTATWFAY, RASQSISDYLH, YASQSIS, and QNGHSFPLT.

  1. The antibody approach of labeling blood cells

    International Nuclear Information System (INIS)

    Srivastava, S.C.

    1992-01-01

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are critically assessed and evaluated

  2. Immunotherapy with GD2 specific monoclonal antibodies

    International Nuclear Information System (INIS)

    Cheung, N.K.V.; Medof, E.M.; Munn, D.

    1988-01-01

    Targeted immunotherapy focuses anti-tumor activity of antibodies and effector cells, which are actively developed by the host or adoptively transferred, onto tumor cells and into tumor sites. Such tumor selective therapy can be more specific and efficient. The value of such an approach is evident in the classical interaction of antibodies. This paper reports that the ganglioside G D2 is an ideal antigen for specific tumor targeting because of its relative lack of heterogeneity among human neuroblastoma, its high density on tumor cells, its lack of antigen modulation upon binding to antibody, and its restricted distribution in normal tissues

  3. The antibody approach of labeling blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.

    1991-12-31

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are criticality assessed and evaluated.

  4. The antibody approach of labeling blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.

    1991-01-01

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are criticality assessed and evaluated.

  5. The antibody approach of labeling blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.

    1992-12-31

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are critically assessed and evaluated.

  6. The antibody approach of labeling blood cells

    International Nuclear Information System (INIS)

    Srivastava, S.C.

    1991-01-01

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are criticality assessed and evaluated

  7. Antiphospholipid antibody syndrome complicated by Grave's disease.

    Science.gov (United States)

    Takahashi, Ayumi; Tamura, Atsushi; Ishikawa, Osamu

    2002-12-01

    The report describes a woman with primary antiphospholipid antibody syndrome complicated with Grave's disease. Developing symptoms included a small cutaneous nodule on her finger and subsequently ecchymotic purpura on the cheeks, ears, buttocks and lower legs. Histological examinations showed thrombosed vessels in the dermis without or with hemorrhage, respectively. Laboratory investigation revealed positive lupus anticoagulant and immunogenic hyperthyroidism due to Grave's disease. There is a close relationship between the cutaneous manifestation of antiphospholipid antibody syndrome and the activities of Grave's disease and a possible link of antiphospholipid antibody syndrome with Grave's disease was suggested both by the etiology of the disease as well as the disease activity.

  8. Reshaping Human Antibodies: Grafting an Antilysozyme Activity

    Science.gov (United States)

    Verhoeyen, Martine; Milstein, Cesar; Winter, Greg

    1988-03-01

    The production of therapeutic human monoclonal antibodies by hybridoma technology has proved difficult, and this has prompted the ``humanizing'' of mouse monoclonal antibodies by recombinant DNA techniques. It was shown previously that the binding site for a small hapten could be grafted from the heavy-chain variable domain of a mouse antibody to that of a human myeloma protein by transplanting the hypervariable loops. It is now shown that a large binding site for a protein antigen (lysozyme) can also be transplanted from mouse to human heavy chain. The success of such constructions may be facilitated by an induced-fit mechanism.

  9. Entamoeba histolytica and E. dispar trophozoites in the liver of hamsters: in vivo binding of antibodies and complement

    Directory of Open Access Journals (Sweden)

    Gomes Maria A

    2010-03-01

    inoculated with E. dispar. Conclusion Morphological and immunohistochemical results suggest that antibodies and complement are able to bind and destroy some trophozoites in the liver of experimentally infected hamsters, perhaps selecting the more resistant parasites which are responsible by progression of amoebic abscesses. The findings indicate that E. histolytica possesses an enhanced ability in vivo to evade the immune responses compared to E. dispar, although it also causes experimental hepatic lesions.

  10. Advances in recombinant antibody manufacturing.

    Science.gov (United States)

    Kunert, Renate; Reinhart, David

    2016-04-01

    Since the first use of Chinese hamster ovary (CHO) cells for recombinant protein expression, production processes have steadily improved through numerous advances. In this review, we have highlighted several key milestones that have contributed to the success of CHO cells from the beginning of their use for monoclonal antibody (mAb) expression until today. The main factors influencing the yield of a production process are the time to accumulate a desired amount of biomass, the process duration, and the specific productivity. By comparing maximum cell densities and specific growth rates of various expression systems, we have emphasized the limiting parameters of different cellular systems and comprehensively described scientific approaches and techniques to improve host cell lines. Besides the quantitative evaluation of current systems, the quality-determining properties of a host cell line, namely post-translational modifications, were analyzed and compared to naturally occurring polyclonal immunoglobulin fractions from human plasma. In summary, numerous different expression systems for mAbs are available and also under scientific investigation. However, CHO cells are the most frequently investigated cell lines and remain the workhorse for mAb production until today.

  11. Systemic radiotherapy with monoclonal antibodies

    International Nuclear Information System (INIS)

    Sautter-Bihl, M.L.; Matzku, S.; Bihl, H.

    1993-01-01

    In this experimental study, feasibility and efficiency of systematic radiotherapy with the I-131 labelled monoclonal antibody BW575/9 (radioimmunotherapy) are investigated using human SK-N-SH neuroblastoma transplated into nude mice. Series of six nude mice were treated with intravenous application of 400 μCi (group 1), 700 μCi (group 2) of the I-131 labelled and of the unlabelled MAb (group 3). An untreated group (group 4) served as control. Tumors of group (3) and (4) showed an identical growth. In group (1), tumor growth was arrested for seven days. In group (2), the tumor showed complete regression after eight days which lasted for 55 days. Thereafter, the tumor started to regrow. This growth characteristics are correlated with the doses achieved in the tumor using a medical radiation dose (MIRD) formulation. The biodistribution data necessary for MIRD calculation were obtained by previously performed experiments with the I-125 labelled MAb. The doses assessed in the tumor turned out to be five to ten times greater than those in normal tissues (liver, bone, etc.) These results confirm feasibility, selectivity and efficiency of radioimmunotherapy in the above described model. Moreover, this in vivo model seems suitable for further investigations concerning fundamental issues of radioimunotherapy. (orig.) [de

  12. Monoclonal antibodies against plant viruses

    International Nuclear Information System (INIS)

    Sandler, E.; Dietzgen, R.G.

    1984-01-01

    Ever since antigenic properties of plant viruses were discovered antisera have been raised and used for plant virus diagnosis and for the analysis of virus structure as well. From the early qualitative diagnosis method of precipitating the virus in clarified sap of an infected plant and the first quantitative application of the precipitin test vast progress has been made with regard to the development of highly sensitive and highly quantitative methods for virus detection. Of equal importance was the improvement of methods for separating virus from host cell components since the specificity of antisera raised against a virus could be increased by using an antigen for immunization highly concentrated and largely freed from contaminating host substances. The introduction of the enzyme-linked immunosorbent assay (ELISA) into plant virology allows detection of virus in nanogram quantities. Still, the conventionally raised antisera, no matter how pure an antigen was used for immunization, are polyclonal. They contain products of thousands of different antibody-secreting plasma cell clones which can be directed against all antigenic determinants (epitopes) of the virus, but also against antigens of the host plant that may not have been entirely separated from the immunizing virus during the purification procedure. Even after cross adsorption of polyclonal antisera some residual heterogeneity can be expected to remain. Within these boundaries the information gained with polyclonal antisera on virus structure and on virus diagnosis has to be interpreted

  13. Radioimmunological proof of thyroglobulin antibodies in humans by the use of a double antibody method

    International Nuclear Information System (INIS)

    Waller, V.

    1982-01-01

    Thyroid antibodies, especially thyroglobulin antibodies, allow themselves to be proven with the double antibody method, in competitive radio binding assays and with the solid phase technique. These methods offer advantages relative to sensitivity and quantifiability. In this work a sensitive radioimmunoassay as a double antibody method was worked out whereby a 125 I-thyroglobulin/thyroglobulin antibody immune complex was precipitated out using anti-human immunoglobulin. The measured results from the radioimmunoassay show a good correlation with the results of the immune histological findings. A high to very high Tg antibody level occurs with autoimmune thyroiditis (80%), primary hypothyroidism (74%) and hyperthyroidism (70%). The control values with healthy people came to less than 5% specific binding. In correlation with the results of other authors this method is advantageous relative to test start and evaluation procedures. (orig.) [de

  14. Basics of Antibody Phage Display Technology.

    Science.gov (United States)

    Ledsgaard, Line; Kilstrup, Mogens; Karatt-Vellatt, Aneesh; McCafferty, John; Laustsen, Andreas H

    2018-06-09

    Antibody discovery has become increasingly important in almost all areas of modern medicine. Different antibody discovery approaches exist, but one that has gained increasing interest in the field of toxinology and antivenom research is phage display technology. In this review, the lifecycle of the M13 phage and the basics of phage display technology are presented together with important factors influencing the success rates of phage display experiments. Moreover, the pros and cons of different antigen display methods and the use of naïve versus immunized phage display antibody libraries is discussed, and selected examples from the field of antivenom research are highlighted. This review thus provides in-depth knowledge on the principles and use of phage display technology with a special focus on discovery of antibodies that target animal toxins.

  15. A novel polyclonal antibody against human cytomegalovirus ...

    African Journals Online (AJOL)

    User

    2011-05-09

    May 9, 2011 ... The identification of the synthetic peptide antibody was confirmed by ... cell virus transmission and fusion of infected cells, as well ..... Cytomegalovirus and Epstein-. Barr virus subtypes-The search for clinical significance.

  16. Localization of tumors by radiolabelled antibodies

    International Nuclear Information System (INIS)

    Hansen, H.J.; Primus, F.J.

    1975-01-01

    A method of utilizing radiolabelled antibodies to carcinoembryonic antigens for determining the site of tumors which produce or are associated with carcinoembryonic antigen is disclosed. 3 claims, no drawings

  17. Patient-Derived Antibody Targets Tumor Cells

    Science.gov (United States)

    An NCI Cancer Currents blog on an antibody derived from patients that killed tumor cells in cell lines of several cancer types and slowed tumor growth in mouse models of brain and lung cancer without evidence of side effects.

  18. Monoclonal antibodies in oncology. Review article

    Energy Technology Data Exchange (ETDEWEB)

    Chan, S Y.T.; Sikora, K

    1986-05-01

    Monoclonal antibodies (MCAs) can be used to differentiate between normal and neoplastic cells and thus exploited for diagnostic and, ultimately, therapeutic gain. The evidence for the existence of human tumour antigens is reviewed. Several areas of diagnosis are already benefiting from the application of the monoclonal technology. Immunohistology can help the pathologist with difficult diagnostic problems. New classifications of lymphoma and leukaemia can be based on specific surface molecules. Similarly, the detection of shed tumour antigens is already established as part of the routine assessment of many patients with common solid tumours. Isotopically labeled monoclonal antibodies have been used to localise primary and metastatic tumours. The use of antibodies in this way is not only a promising diagnostic tool but also the first step in studying the possibility of arming antibodies to provide therapeutic agents. Such trials are currently in progress. 69 refs.; 7 figs.; 3 tabs.

  19. Monoclonal antibody therapy of inflammatory bowel disease

    NARCIS (Netherlands)

    van Deventer, S. J.; Camoglio, L.

    1997-01-01

    Animal models of inflammatory bowel disease have provided insight in the regulation of mucosal inflammation. This has resulted in novel therapeutic approaches that specifically target a single inflammatory mediator. Monoclonal antibody therapy has been used in steroid refractory Crohn's disease

  20. Antibody conjugate radioimmunotherapy of superficial bladder cancer

    International Nuclear Information System (INIS)

    Perkins, Alan; Hopper, Melanie; Murray, Andrea; Frier, Malcolm; Bishop, Mike

    2002-01-01

    The administration of antibody conjugates for cancer therapy is now proving to be of clinical value. We are currently undertaking a programme of clinical studies using the monoclonal antibody C 595 (gG3) which reacts with the MUC1 glycoprotein antigen that is aberrantly expressed in a high proportion of bladder tumours. Radio immuno conjugates of the C 595 antibody have been produced with high radiolabelling efficiency and immuno reactivity using Tc-99 m and In-111 for diagnostic imaging, and disease staging and the cytotoxic radionuclides Cu-67 and Re-188 for therapy of superficial bladder cancer. A Phase I/II therapeutic trail involving the intravesical administration of antibody directly into the bladder has now begun. (author)

  1. Enhanced Phagocytosis and Antibody Production by Tinospora ...

    African Journals Online (AJOL)

    SERVER

    2008-01-18

    Jan 18, 2008 ... antibody production through in vitro and in vivo studies. MATERIALS AND METHODS. Collection ..... components with candidicidal activity in human, rabbit and guinea pig leukocytes. Infect. Immun., 11: 1226-1234. Manjrekar ...

  2. Determination of antiphospholipid antibodies and Thrombophilia in ...

    African Journals Online (AJOL)

    Determination of antiphospholipid antibodies and Thrombophilia in women ... frequency of the primary and secondary antiphospholipid syndrome and the ... in between or with medical termination of pregnancy were excluded from this study.

  3. [Possibilities of differentiation of antinuclear antibodies].

    Science.gov (United States)

    Müller, W; Rosenthal, M; Stojan, B

    1975-10-15

    Antinuclear antibodies can give diagnostic informations according to their titre values, the belonging to different classes of immune globulins and on the basis of different patterns of immunofluorescence connection. The determination of granulocyte-specific antibodies which frequently appear in progressive chronic polyarthritis further contributes to the differential-diagnostic classification of diseases of the connective tissue. An antibody against extractable nuclear antigen is specific for the so-called mixed connective tissue disease, an antimitochondrial antibody for the pseudo-LE-syndrome. Moreover, the own examinations resulted in a particularly high and frequent ability of complement fixation of the antinuclear factors in systematic lupus erythematosus and sclerodermy. In contrast to this in the progressive chronic polyarthritis the complement fixation was clearly more insignificant.

  4. Targeting Malignant Brain Tumors with Antibodies

    Directory of Open Access Journals (Sweden)

    Rok Razpotnik

    2017-09-01

    Full Text Available Antibodies have been shown to be a potent therapeutic tool. However, their use for targeting brain diseases, including neurodegenerative diseases and brain cancers, has been limited, particularly because the blood–brain barrier (BBB makes brain tissue hard to access by conventional antibody-targeting strategies. In this review, we summarize new antibody therapeutic approaches to target brain tumors, especially malignant gliomas, as well as their potential drawbacks. Many different brain delivery platforms for antibodies have been studied such as liposomes, nanoparticle-based systems, cell-penetrating peptides (CPPs, and cell-based approaches. We have already shown the successful delivery of single-chain fragment variable (scFv with CPP as a linker between two variable domains in the brain. Antibodies normally face poor penetration through the BBB, with some variants sufficiently passing the barrier on their own. A “Trojan horse” method allows passage of biomolecules, such as antibodies, through the BBB by receptor-mediated transcytosis (RMT. Such examples of therapeutic antibodies are the bispecific antibodies where one binding specificity recognizes and binds a BBB receptor, enabling RMT and where a second binding specificity recognizes an antigen as a therapeutic target. On the other hand, cell-based systems such as stem cells (SCs are a promising delivery system because of their tumor tropism and ability to cross the BBB. Genetically engineered SCs can be used in gene therapy, where they express anti-tumor drugs, including antibodies. Different types and sources of SCs have been studied for the delivery of therapeutics to the brain; both mesenchymal stem cells (MSCs and neural stem cells (NSCs show great potential. Following the success in treatment of leukemias and lymphomas, the adoptive T-cell therapies, especially the chimeric antigen receptor-T cells (CAR-Ts, are making their way into glioma treatment as another type of cell

  5. Imaging of colorectal carcinoma with radiolabeled antibodies.

    Science.gov (United States)

    Goldenberg, D M; Goldenberg, H; Sharkey, R M; Lee, R E; Higgenbotham-Ford, E; Horowitz, J A; Hall, T C; Pinsky, C M; Hansen, H J

    1989-10-01

    Colorectal cancer has been the tumor type most frequently studied with radiolabeled antibodies. Among the various antibodies, a majority of patients with colorectal cancer have received xenogeneic polyclonal or monoclonal antibodies against carcino-embryonic antigen. This review summarizes the current status of colorectal cancer imaging with radiolabeled antibodies, ie, radioimmunodetection (RAID), and examines the published studies involving carcinoembryonic antigen (CEA) antibodies and 17-1A, 19-9, and B72.3, and other monoclonal antibodies. In order to better address the issue of the current and future clinical usefulness of this emerging technology, particular attention is given to the protocols, methods, and results of the published studies. Despite differences in study parameters, antibodies and forms, labels, administration routes and doses, and scanning instruments and methods, it has been found that (1) almost no adverse reactions have been evident; (2) antibody fragments are preferred over whole immunoglobulin G reagents because they achieve higher tumor-to-background ratios earlier, thus reducing or precluding the need for dual-isotope subtraction methods or long delays before imaging; (3) use of antibody fragments, including the monovalent Fab' form, permits imaging with short-lived radionuclides of excellent photon properties, such as 123I and 99mTc; (4) circulating antigens against which the imaging antibody is directed can complex with the injected antibody, but such complexes have not prevented successful RAID; (5) patients with high serum titers of the appropriate antigen target usually have higher rates of positive RAID; (6) patients who are seronegative for the tumor antigen being studied can have positive RAID findings, which can represent the detection of occult lesions; (7) single photon emission computed tomography appears to provide better image resolution than planar scanning; (8) regardless of the sensitivity reported in any particular

  6. Delineation of pulmonary airway fluid protein fractions with HRPO binding-avidity by far-Western ligand blot and mass spectrometry analyses: a model methodology for detecting mannose-binding protein expression profiles.

    Science.gov (United States)

    Coyne, Cody P; Rashmir-Raven, Ann; Jones, Toni; Mochal, Cathleen; Linford, Robert L; Brashier, Michael; Eddy, Alison

    2009-01-01

    Limited research to date has characterized the potential for HRPO to function as a primary molecular probe. Pulmonary airway fluid was developed by non-reducing far-Western (ligand) blot analyses utilizing conjugated HRPO-strepavidin or non-conjugated HRPO without the presence of primary immunoglobulin. Endogenous esterase-like biochemical activity of fractions within pulmonary airway fluid was inactivated to determine if they were capable of biochemically converting HRPO chemiluminescent substrate. Complementary analyses modified pulmonary fluid and HRPO with beta-galactosidase and alpha-mannosidase respectively, in addition to determining the influence of mannose and maltose competitive binding on HRPO far-Western (ligand) blot analyses. Identification of pulmonary fluid fractions detected by HRPO far-Western blot analyses was determined by mass spectrometry. Modification of pulmonary fluid with beta-galactosidase, and HRPO with alpha-mannosidase in concert with maltose and mannose competitive binding analyses altered the intensity and spectrum of pulmonary fluid fractions detected by HRPO far-Western blot analysis. Identity of pulmonary airway fluid fractions detected by HRPO far-Western (ligand) blot analysis were transferrin, dynein, albumin precursor, and two 156 kDa equine peptide fragments. HRPO can function as a partially-selective primary molecular probe when applied in either a conjugated or non-conjugated form. Some protein fractions can form complexes with HRPO through molecular mechanisms that involve physical interactions at the terminal alpha-mannose-rich regions of HRPO glycan side-chains. Based on its known molecular composition and structure, HRPO provides an opportunity for the development of diagnostics methodologies relevant to disease biomarkers that possess mannose-binding avidity.

  7. Generalized Platform for Antibody Detection using the Antibody Catalyzed Water Oxidation Pathway

    OpenAIRE

    Welch, M. Elizabeth; Ritzert, Nicole L.; Chen, Hongjun; Smith, Norah L.; Tague, Michele E.; Xu, Youyong; Baird, Barbara A.; Abru?a, H?ctor D.; Ober, Christopher K.

    2014-01-01

    Infectious diseases, such as influenza, present a prominent global problem including the constant threat of pandemics that initiate in avian or other species and then pass to humans. We report a new sensor that can be specifically functionalized to detect antibodies associated with a wide range of infectious diseases in multiple species. This biosensor is based on electrochemical detection of hydrogen peroxide generated through the intrinsic catalytic activity of all antibodies: the antibody ...

  8. An indirect antibody assay using haptenated antigen and 125I-labelled anti-hapten antibody

    International Nuclear Information System (INIS)

    Aalberse, R.C.; Amsterdam Univ.

    1978-01-01

    Hapten (trinitrophenyl) was coupled to antigen (ovalbumin). The haptenated antigen was bound by anti-ovalbumin antibody and binding was quantitated with 125 I-labelled anti-hapten antibodies. Thus, with a single radioactive reagent, antibodies against a variety of antigens can be detected while the problems inherent in a labelled antiglobulin binding test are avoided. In the ovalbumin system, the haptenated antigen binding test proved to be approximately 20 times as sensitive as the iodinated ovalbumin binding test

  9. Antibody recognition of Z-DNA

    International Nuclear Information System (INIS)

    Lafer, E.M.; Moeller, A.; Valle, R.P.C.; Nordheim, V.A.; Rich, A.; Stollar, B.D.; Massachusetts Inst. of Tech., Cambridge)

    1983-01-01

    To measure serological reactions under physiological ionic strength, we prepared a brominated (Bl) poly(dG-dC).poly(dG-dC), which forms a stable Z helix in solutions of low salt concentration. Mice and rabbits were immunized with this polymer complexed with the basic protein methylated bovine serum albumin (MBSA), and it was discovered that the Z-DNA helix is a strong immunogen. Various antibody populations were purified from the rabbit serum by quantitative immunoprecipitation. Spleen cells from the mice were used for the preparation of hybridoma cell lines secreting monoclonal antibodies. Anti-Z-DNA antibodies were also raised by immunizing animals with poly(dG-dm 5 C).poly(dG-dm 5 C) under conditions where it was reported to be in the left-handed Z conformation as well as unmodified poly(dG-dC).poly(dG-dC) that was in the right-handed B conformation: both were complexed with MBSA. Z-DNA reactive antibodies were found in both murine and human SLE. A Z-DNA-specific as well as a dDNA and Z-DNA cross-reactive antibody population were distinguished by affinity chromatography of the SLE sera. The specificities of the various anti-Z-DNA antibody populations were measured by direct-binding and competitive radioimmunoassays, using synthetic polymers of defined structure under various ionic strengths. These studies allow us to map the possible antigenic sites for these antibodies, which serve as a model for DNA-protein recognition. The findings also established the usefulness of the antibodies as biochemical probes for Z-DNA. 29 references, 6 figures, 1 table

  10. Radioimmunoassay of measles virus antibodies in SSPE

    International Nuclear Information System (INIS)

    Jankowski, M.A.; Gut, W.; Kantoch, M.

    1982-01-01

    A sensitive radioimmunoassay (RIA) was introduced for detecting measles virus IgG and IgM antibodies. The hyperimmune response to the measles virus could be demonstrated more accurately by RIA than by haemagglutination inhibition (HI). The ratio between RIA and HI antibody titres was decidedly higher in sera and cerebrospinal fluids of patients with subacute sclerosing panencephalitis than in those of other groups tested. (author)

  11. Brain-Reactive Antibodies and Disease

    OpenAIRE

    Diamond, B.; Honig, G.; Mader, S.; Brimberg, L.; Volpe, B.T.

    2013-01-01

    Autoimmune diseases currently affect 5–7% of the world's population; in most diseases there are circulating autoantibodies. Brain-reactive antibodies are present in approximately 2–3% of the general population but do not usually contribute to brain pathology. These antibodies penetrate brain tissue only early in development or under pathologic conditions. This restriction on their pathogenicity and the lack of correlation between serum titers and brain pathology have, no doubt, contributed to...

  12. Antibody repertoire profiling with mimotope arrays

    OpenAIRE

    Pashova, Shina; Schneider, Christoph; von Gunten, Stephan; Pashov, Anastas

    2016-01-01

    Large-scale profiling and monitoring of antibody repertoires is possible through next generation sequencing (NGS), phage display libraries and microarrays. These methods can be combined in a pipeline, which ultimately maps the antibody reactivities onto defined arrays of structures - peptides or carbohydrates. The arrays can help analyze the individual specificities or can be used as complex patterns. In any case, the targets recognized should formally be considered mimotopes unless they are ...

  13. [Limbic encephalitis with antibodies against intracellular antigens].

    Science.gov (United States)

    Morita, Akihiko; Kamei, Satoshi

    2010-04-01

    Limbic encephalitis is a paraneoplastic syndrome that is often associated with small cell lung cancer (SCLC), breast cancer, testicular tumors, teratoma, Hodgkin's lymphoma and thymoma. The common clinical manifestations of limbic encephalitis are subacute onset, cognitive dysfunction, seizures and psychiatric symptoms. Paraneoplastic neurological disorders are considered to occur because of cytotoxic T cell responses and antibodies against target neuronal proteins that are usually expressed by an underlying tumor. The main intracellular antigens related to limbic encephalitis are Hu, Ma2, and less frequently CV2/CRMP5 and amphiphysin. The anti-Hu antibody, which is involved in cerebellar degeneration and extensive or multifocal encephalomyelitis such as limbic encephalitis is closely associated with a history of smoking and SCLC. The anti-Ma2 antibody is associated with encephalitis of the limbic system, hypothalamus and brain-stem. For this reason, some patients with limbic encephalitis have sleep disorders (including REM sleep abnormalities), severe hypokinesis and gaze palsy in addition to limbic dysfunction. In men aged less than 50 years, anti-Ma2 antibody encephalitis is almost always associated with testicular germ-cell tumors that are occasionally difficult to detect. In older men and women, the most common tumors are non-SCLC and breast cancer. Limbic encephalitis associated with cell-surface antigens (e.g., voltage-gated potassium channels, NMDA receptors) is mediated by antibodies and often improves after a reduction in the antibody titer and after tumor resection. Patients with antibodies against intracellular antigens, except for those with anti-Ma2 antibodies and testicular tumors, are less responsive. Early diagnosis and treatment with immunotherapy, tumor resection or both are important for improving or stabilizing the condition of limbic encephalitis.

  14. Antibody or Antibody Fragments: Implications for Molecular Imaging and Targeted Therapy of Solid Tumors

    Directory of Open Access Journals (Sweden)

    Katerina T. Xenaki

    2017-10-01

    Full Text Available The use of antibody-based therapeutics has proven very promising for clinical applications in cancer patients, with multiple examples of antibodies and antibody–drug conjugates successfully applied for the treatment of solid tumors and lymphomas. Given reported recurrence rates, improvements are clearly still necessary. A major factor limiting the efficacy of antibody-targeted cancer therapies may be the incomplete penetration of the antibody or antibody–drug conjugate into the tumor. Incomplete tumor penetration also affects the outcome of molecular imaging, when using such targeting agents. From the injection site until they arrive inside the tumor, targeting molecules are faced with several barriers that impact intratumoral distribution. The primary means of antibody transport inside tumors is based on diffusion. The diffusive penetration inside the tumor is influenced by both antibody properties, such as size and binding affinity, as well as tumor properties, such as microenvironment, vascularization, and targeted antigen availability. Engineering smaller antibody fragments has shown to improve the rate of tumor uptake and intratumoral distribution. However, it is often accompanied by more rapid clearance from the body and in several cases also by inherent destabilization and reduction of the binding affinity of the antibody. In this perspective, we discuss different cancer targeting approaches based on antibodies or their fragments. We carefully consider how their size and binding properties influence their intratumoral uptake and distribution, and how this may affect cancer imaging and therapy of solid tumors.

  15. [Screening serum response special antibodies of U251 cell line from surface display phage antibody library].

    Science.gov (United States)

    Yu, Min; Tan, De-Yong; Qian, Wei; Lai, Jian-Hua; Sun, Gui-Lin

    2004-05-01

    U251 cell is a sensitive cell line to serum, which stops at G0 phase of cell cycle in no-serum medium, and recovers growth when the serum is added into no-serum medium. The cell can express corresponding proteins in different phase of cell cycle. Therefore it is very signification for the study of cell cycle regulation mechanism that explores these proteins. In this paper, the mouse antibody phage display library was added into the bottle in which the serum starvation U251 cells had been cultured, and the special antibody phages were absorbed. Then the absorbed antibody phages were amplified by adding E. coli TG1 and helper phage M13K07. Amplified antibody phages were added into bottle in which the serum cultured cell after serum starvation (follow named as serum recovered cells) were incubated, so that the cell absorbed the no-special antibody phages for the serum starvation cell and the special antibody phages were in supernatant. The remaining no-special antibody phages in the supernatant were discarded by repeating above program 3-4 times. The pure special antibody phages were gotten, and amplified by adding the host cell E. coli TG1 and helper phage M13K07. Then the host bacterium infected special antibody phage was spread on the plate medium with ampicillin, and the monoclonal antibody phages were gotten. Using same as above program, the monoclonal antibody phages absorbed specially for serum recovered U251 cells were obtained when the serum recovered cells instead of serum starvation cells and serum starvation cells instead of serum recovered cells. In this study, ninety-six positive monoclonal antibody phages that absorbed specially the serum starvation cells and eighty-two positive monoclonal antibody phages that absorbed specially the serum recovered cells were obtained. By using cell immunochemistry assay, two special signification antibodies were obtained. one (No.11) was the strong response in serum starvation cells, the other (No.2) was the strong

  16. Complement-fixing antibodies against denatured HLA and MICA antigens are associated with antibody mediated rejection.

    Science.gov (United States)

    Cai, Junchao; Terasaki, Paul I; Zhu, Dong; Lachmann, Nils; Schönemann, Constanze; Everly, Matthew J; Qing, Xin

    2016-02-01

    We have found antibodies against denatured HLA class I antigens in the serum of allograft recipients which were not significantly associated with graft failure. It is unknown whether transplant recipients also have denatured HLA class II and MICA antibodies. The effects of denatured HLA class I, class II, and MICA antibodies on long-term graft outcome were further investigated based on their ability to fix complement c1q. In this 4-year retrospective cohort study, post-transplant sera from 975 kidney transplant recipients were tested for antibodies against denatured HLA/MICA antigens and these antibodies were further classified based on their ability to fix c1q. Thirty percent of patients had antibodies against denatured HLA class I, II, or MICA antigens. Among them, 8.5% and 21.5% of all patients had c1q-fixing and non c1q-fixing antibodies respectively. There was no significant difference on graft survival between patients with or without antibodies against denatured HLA/MICA. However, when these antibodies were further classified according to their ability to fix c1q, patients with c1q-fixing antibodies had a significantly lower graft survival rate than patients without antibodies or patients with non c1q-fixing antibodies (p=0.008). In 169 patients who lost renal grafts, 44% of them had c1q-fixing antibodies against denatured HLA/MICA antigens, which was significantly higher than that in patients with functioning renal transplants (25%, pantibodies were more significantly associated with graft failure caused by AMR (72.73%) or mixed AMR/CMR (61.9%) as compared to failure due to CMR (35.3%) or other causes (39.2%) (p=0.026). Transplant recipients had antibodies against denatured HLA class I, II, and MICA antigens. However, only c1q-fixing antibodies were associated with graft failure which was related to antibody mediated rejection. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Generation of HER2 monoclonal antibodies using epitopes of a rabbit polyclonal antibody.

    Science.gov (United States)

    Hu, Francis Jingxin; Uhlen, Mathias; Rockberg, Johan

    2014-01-25

    One of the issues in using polyclonal antibodies is the limited amount of reagent available from an immunisation, leading to batch-to-batch variation and difficulties in obtaining the same antibody performance when the same antigen is re-immunised into several separate animals. This led to the development of hybridoma technology allowing, at least theoretically, for an unlimited production of a specific binder. Nevertheless, polyclonal antibodies are widely used in research and diagnostics and there exists a need for robust methods to convert a polyclonal antibody with good binding performance into a renewable monoclonal with identical or similar binding specificity. Here we have used precise information regarding the functional recognition sequence (epitope) of a rabbit polyclonal antibody with attractive binding characteristics as the basis for generation of a renewable mouse monoclonal antibody. First, the original protein fragment antigen was used for immunisation and generation of mouse hybridoma, without obtaining binders to the same epitope region. Instead a peptide designed using the functional epitope and structural information was synthesised and used for hybridoma production. Several of the monoclonal antibodies generated were found to have similar binding characteristics to those of the original polyclonal antibody. These monoclonal antibodies detected native HER2 on cell lines and were also able to stain HER2 in immunohistochemistry using xenografted mice, as well as human normal and cancer tissues. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. [Construction of human phage antibody library and screening for human monoclonal antibodies of amylin].

    Science.gov (United States)

    Gong, Qian; Li, Chang-ying; Chang, Ji-wu; Zhu, Tie-hong

    2012-06-01

    To screen monoclonal antibodies to amylin from a constructed human phage antibody library and identify their antigenic specificity and combining activities. The heavy chain Fd fragment and light chain of human immunoglobulin genes were amplified from peripheral blood lymphocytes of healthy donors using RT-PCR, and then inserted into phagemid pComb3XSS to generate a human phage antibody library. The insertion of light chain or heavy chain Fd genes were identified by PCR after the digestion of Sac I, Xba I, Xho Iand Spe I. One of positive clones was analyzed by DNA sequencing. The specific anti-amylin clones were screened from antibody library against human amylin antigens and then the positive clones were determined by Phage-ELISA analysis. A Fab phage antibody library with 0.8×10(8); members was constructed with the efficacy of about 70%. DNA sequence analysis indicated V(H); gene belonged to V(H);3 gene family and V(λ); gene belonged to the V(λ); gene family. Using human amylin as panning antigen, specific anti-amylin Fab antibodies were enriched by screening the library for three times. Phage-ELISA assay showed the positive clones had very good specificity to amylin antigen. The successful construction of a phage antibody library and the identification of anti-amylin Fab antibodies provide a basis for further study and preparation of human anti-amylin antibodies.

  19. Microangiopathic antiphospholipid antibody syndrome due to anti-phosphatidylserine/prothrombin complex IgM antibody.

    Science.gov (United States)

    Senda, Yumi; Ohta, Kazuhide; Yokoyama, Tadafumi; Shimizu, Masaki; Furuichi, Kengo; Wada, Takashi; Yachie, Akihiro

    2017-03-01

    Herein we describe a case of microangiopathic antiphospholipid syndrome (MAPS) due to anti-phosphatidylserine/prothrombin complex (aPS/PT) IgM antibody successfully treated with rituximab. A significant correlation was observed between the clinical course and the aPS/PT IgM antibody titer, which can rise earlier before the appearance of clinical symptoms. Rituximab can be safely and effectively used for MAPS. Although detection of only aPS/PT IgM antibody is rare, aPS/PT IgM antibody might be associated with the pathogenesis of MAPS and might be a useful marker of disease activity. © 2017 Japan Pediatric Society.

  20. Construction of human antibody gene libraries and selection of antibodies by phage display.

    Science.gov (United States)

    Frenzel, André; Kügler, Jonas; Wilke, Sonja; Schirrmann, Thomas; Hust, Michael

    2014-01-01

    Antibody phage display is the most commonly used in vitro selection technology and has yielded thousands of useful antibodies for research, diagnostics, and therapy.The prerequisite for successful generation and development of human recombinant antibodies using phage display is the construction of a high-quality antibody gene library. Here, we describe the methods for the construction of human immune and naive scFv gene libraries.The success also depends on the panning strategy for the selection of binders from these libraries. In this article, we describe a panning strategy that is high-throughput compatible and allows parallel selection in microtiter plates.

  1. Lichen planus, liver kidney microsomal (LKM1) antibodies and hepatitis C virus antibodies.

    Science.gov (United States)

    Divano, M C; Parodi, A; Rebora, A

    1992-01-01

    No anti-liver kidney microsomal (LKM1) antibodies were detected in 46 patients with LP, 16 of whom had also a chronic liver disease (CLD). In contrast, anti-hepatitis C virus (HCV) antibodies were found in 10% of patients with LP and in 50% of those with LP and CLD. Anti-HCV antibodies may be considered as a false-positive reaction in 56% of cases, especially when anti-LKM1 antibodies are present. Our findings do not support such a hypothesis, but suggest that CLD in LP patients is, at least in Italy, mostly a postviral chronic active hepatitis.

  2. Boosting antibody developability through rational sequence optimization.

    Science.gov (United States)

    Seeliger, Daniel; Schulz, Patrick; Litzenburger, Tobias; Spitz, Julia; Hoerer, Stefan; Blech, Michaela; Enenkel, Barbara; Studts, Joey M; Garidel, Patrick; Karow, Anne R

    2015-01-01

    The application of monoclonal antibodies as commercial therapeutics poses substantial demands on stability and properties of an antibody. Therapeutic molecules that exhibit favorable properties increase the success rate in development. However, it is not yet fully understood how the protein sequences of an antibody translates into favorable in vitro molecule properties. In this work, computational design strategies based on heuristic sequence analysis were used to systematically modify an antibody that exhibited a tendency to precipitation in vitro. The resulting series of closely related antibodies showed improved stability as assessed by biophysical methods and long-term stability experiments. As a notable observation, expression levels also improved in comparison with the wild-type candidate. The methods employed to optimize the protein sequences, as well as the biophysical data used to determine the effect on stability under conditions commonly used in the formulation of therapeutic proteins, are described. Together, the experimental and computational data led to consistent conclusions regarding the effect of the introduced mutations. Our approach exemplifies how computational methods can be used to guide antibody optimization for increased stability.

  3. Antibody-Conjugated Nanoparticles for Biomedical Applications

    Directory of Open Access Journals (Sweden)

    Manuel Arruebo

    2009-01-01

    Full Text Available Nanoscience and Nanotechnology have found their way into the fields of Biotechnology and Medicine. Nanoparticles by themselves offer specific physicochemical properties that they do not exhibit in bulk form, where materials show constant physical properties regardless of size. Antibodies are nanosize biological products that are part of the specific immune system. In addition to their own properties as pathogens or toxin neutralizers, as well as in the recruitment of immune elements (complement, improving phagocytosis, cytotoxicity antibody dependent by natural killer cells, etc., they could carry several elements (toxins, drugs, fluorochroms, or even nanoparticles, etc. and be used in several diagnostic procedures, or even in therapy to destroy a specific target. The conjugation of antibodies to nanoparticles can generate a product that combines the properties of both. For example, they can combine the small size of nanoparticles and their special thermal, imaging, drug carrier, or magnetic characteristics with the abilities of antibodies, such as specific and selective recognition. The hybrid product will show versatility and specificity. In this review, we analyse both antibodies and nanoparticles, focusing especially on the recent developments for antibody-conjugated nanoparticles, offering the researcher an overview of the different applications and possibilities of these hybrid carriers.

  4. Anti-glucagon antibodies in diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Gergely, A; Koranyi, L; Halmos, T; Zsombok, M; Peterfy, F; Csizer, Z; Salamon, F; Tako, J

    1973-01-01

    Anti-insulin antibodies appear in the sera of patients treated with insulin lastingly. A high anti-insulin antibody level results in the development of insulin resistance. Most of the insulin preparations available on the market contain also glucagon as an impurity. It was therefore to be expected that in part of the patients, who had been treated with insulin lastingly, antibodies would be produced also against glucagon, and the presence of these was actually demonstrated. It is to be assumed that the anti-glucagon antibodies play a role in the pathomechanism of diabetes mellitus, mainly in its labile form. The possible presence of anti-glucagon antibodies must be taken into account when the glucagon concentration in the sera of diabetics is to be determined by means of radioimmunoassay (RIA). The specific antibodies in the serum give false results in the quantitative determination of glucagon. We have tested the sera of 10 diabetics who had been treated with insulin for at least 6 years. All patients were given protamine zinc and crystalline insulin preparations.

  5. Decay of maternal antibodies in broiler chickens.

    Science.gov (United States)

    Gharaibeh, Saad; Mahmoud, Kamel

    2013-09-01

    The objective of this study was to determine the decay rate of maternal antibodies against major broiler chicken pathogens. A total of 30 one-day-old broiler chicks were obtained from a commercial hatchery and reared in isolation. These chicks were retrieved from a parent flock that received a routine vaccination program. Chicks were bled at hatch and sequentially thereafter every 5 d through 30 d of age. Maternal antibody titers were measured by ELISA for avian encephalomyelitis (AEV), avian influenza virus (AIV), chicken anemia virus (CAV), infectious bursal disease virus (IBDV), infectious bronchitis virus (IBV), infectious laryngotracheitis virus (ILTV), Mycoplasma gallisepticum (MG), Mycoplasma synoviae (MS), and reovirus (Reo). Maternal antibody titers for Newcastle disease virus (NDV) were measured using a hemagglutination inhibition test. Half-life estimates of maternal antibody titers were 5.3, 4.2, 7, 5.1, 3.9, 3.8, 4.9, 4.1, 6.3, and 4.7 d for AEV, AIV, CAV, IBDV, IBV, ILTV, MG, MS, NDV, and Reo, respectively. The statistical analysis revealed significant differences among half-lives of maternal antibody titers against certain pathogens. Furthermore, all maternal antibody titers were depleted by 10 d of age except for IBDV.

  6. The SAATELLITE and EVADE Clinical Studies Within the COMBACTE Consortium: A Public-Private Collaborative Effort in Designing and Performing Clinical Trials for Novel Antibacterial Drugs to Prevent Nosocomial Pneumonia.

    Science.gov (United States)

    François, Bruno; Chastre, Jean; Eggiman, Philippe; Laterre, Pierre-François; Torres, Antoni; Sanchez, Miguel; Esser, Mark T; Bishop, Brian; Bonten, Marc; Goosens, Herman; Jafri, Hasan S

    2016-08-15

    The Innovative Medicines Initiative-funded COMBACTE consortium fosters academic-industry partnership in pioneering studies to combat serious bacterial infections. We describe how this partnership is advancing the development of 2 monoclonal antibodies, MEDI4893 and MEDI3902, for the prevention of nosocomial pneumonia. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  7. Metabolomics reveals distinct, antibody-independent, molecular signatures of MS, AQP4-antibody and MOG-antibody disease.

    Science.gov (United States)

    Jurynczyk, Maciej; Probert, Fay; Yeo, Tianrong; Tackley, George; Claridge, Tim D W; Cavey, Ana; Woodhall, Mark R; Arora, Siddharth; Winkler, Torsten; Schiffer, Eric; Vincent, Angela; DeLuca, Gabriele; Sibson, Nicola R; Isabel Leite, M; Waters, Patrick; Anthony, Daniel C; Palace, Jacqueline

    2017-12-06

    The overlapping clinical features of relapsing remitting multiple sclerosis (RRMS), aquaporin-4 (AQP4)-antibody (Ab) neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-Ab disease mean that detection of disease specific serum antibodies is the gold standard in diagnostics. However, antibody levels are not prognostic and may become undetectable after treatment or during remission. Therefore, there is still a need to discover antibody-independent biomarkers. We sought to discover whether plasma metabolic profiling could provide biomarkers of these three diseases and explore if the metabolic differences are independent of antibody titre. Plasma samples from 108 patients (34 RRMS, 54 AQP4-Ab NMOSD, and 20 MOG-Ab disease) were analysed by nuclear magnetic resonance spectroscopy followed by lipoprotein profiling. Orthogonal partial-least squares discriminatory analysis (OPLS-DA) was used to identify significant differences in the plasma metabolite concentrations and produce models (mathematical algorithms) capable of identifying these diseases. In all instances, the models were highly discriminatory, with a distinct metabolite pattern identified for each disease. In addition, OPLS-DA identified AQP4-Ab NMOSD patient samples with low/undetectable antibody levels with an accuracy of 92%. The AQP4-Ab NMOSD metabolic profile was characterised by decreased levels of scyllo-inositol and small high density lipoprotein particles along with an increase in large low density lipoprotein particles relative to both RRMS and MOG-Ab disease. RRMS plasma exhibited increased histidine and glucose, along with decreased lactate, alanine, and large high density lipoproteins while MOG-Ab disease plasma was defined by increases in formate and leucine coupled with decreased myo-inositol. Despite overlap in clinical measures in these three diseases, the distinct plasma metabolic patterns support their distinct serological profiles and confirm that these

  8. Antibody Scientific Committee | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The Antibody Scientific Committee provides scientific insight and guidance to the NCI's Antibody Characterization Program. Specifically, the members of this committee evaluate request from the external scientific community for development and characterization of antibodies by the program. The members of the Antibody Scientific Committee include:

  9. 21 CFR 866.5100 - Antinuclear antibody immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antinuclear antibody immunological test system....5100 Antinuclear antibody immunological test system. (a) Identification. An antinuclear antibody... the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular nuclear...

  10. Avian Diagnostic and Therapeutic Antibodies to Viral Emerging Pathogens

    Energy Technology Data Exchange (ETDEWEB)

    David Bradley

    2011-03-31

    During the current period the following key objectives were achieved: demonstration of high titer antibody production by geese following immunization with inactived H1N1 virus; completion of the epitope mapping of West Nile Virus-specific goose antibodies and initiation of epitope mapping of H1N1 flu-specific goose antibodies; advancement in scalable purification of goose antibodies.

  11. Monoclonal Antibodies Specific for STAT3β Reveal Its Contribution to Constitutive STAT3 Phosphorylation in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Uddalak Bharadwaj

    2014-09-01

    Full Text Available Since its discovery in mice and humans 19 years ago, the contribution of alternatively spliced Stat3, Stat3β, to the overall functions of Stat3 has been controversial. Tyrosine-phosphorylated (p Stat3β homodimers are more stable, bind DNA more avidly, are less susceptible to dephosphorylation, and exhibit distinct intracellular dynamics, most notably markedly prolonged nuclear retention, compared to pStat3α homodimers. Overexpression of one or the other isoform in cell lines demonstrated that Stat3β acted as a dominant-negative of Stat3α in transformation assays; however, studies with mouse strains deficient in one or the other isoform indicated distinct contributions of Stat3 isoforms to inflammation. Current immunological reagents cannot differentiate Stat3β proteins derived from alternative splicing vs. proteolytic cleavage of Stat3α. We developed monoclonal antibodies that recognize the 7 C-terminal amino acids unique to Stat3β (CT7 and do not cross-react with Stat3α. Immunoblotting studies revealed that levels of Stat3β protein, but not Stat3α, in breast cancer cell lines positively correlated with overall pStat3 levels, suggesting that Stat3β may contribute to constitutive Stat3 activation in this tumor system. The ability to unambiguously discriminate splice alternative Stat3β from proteolytic Stat3β and Stat3α will provide new insights into the contribution of Stat3β vs. Stat3α to oncogenesis, as well as other biological and pathological processes.

  12. Choice of radionuclide for antibody labelling: new perspectives

    International Nuclear Information System (INIS)

    Hazra, D.K.; Dass, S.

    1983-01-01

    The expanding horizons of labelled antibody techniques in diagnostic imaging or assay, therapy and research and the availabilities of monoclonal antibodies is resulting in a demand for suitable radionuclides as antibody labels. An outline is given of the different criteria for choosing an appropriate radionuclide for labelling an antibody depending on its particular field of use. The requirements of procedures for firmly linking radionuclides to antibodies are also given. (U.K.)

  13. Stability of rhenium-188 labeled antibody

    International Nuclear Information System (INIS)

    Lim, B. K.; Jung, J. M.; Jung, J. K.; Lee, D. S.; Lee, M. C.

    1999-01-01

    For clinical application of beta-emitter labeled antibody, high specific activity is important. Carrier-free Re-188 from W-188/Re-188 generator is an ideal radionuclide for this purpose. However, low stability of Re-188 labeled antibody, especially in high specific activity, due to radiolytic decomposition by high energy (2.1 MeV) beta ray was problem. We studied the stability of Re-188 labeled antibody, and stabilizing effect of several nontoxic radical-quenching agents. Pre-reduced monoclonal antibody (CEA79.4) was labeled with Re-188 by incubating with generator-eluted Re-188-perrhenate in the presence of stannous tartrate for 2 hr at room temperature. Radiochemical purity of each preparation was determined by chromatography (ITLC-SG/acetone, ITLC-SG/Umezawa, Whatman No.1/saline). Human serum albumin was added to the labeled antibodies(2%). Stability of Re-188-CEA79.4 was investigated in the presence of vitamin C, ethanol, or Tween 80 as radical-quenching agents. Specific activities of 4.29∼5.11 MBq/μg were obtained. Labeling efficiencies were 88±4%(n=12). Very low stability after removal of stannous tartrate from the preparation was observed. If stored after purging with N 2 , all the preparations were stable for 10 hr. However, if contacted with air, stability decreased. Perrhenate and Re-188-tartrate was major impurity in declined preparation (12∼47 and 9∼38% each, after 10 hr). Colloid-formation was not a significant problem in all cases. Addition of vitamin C stabilized the labeled antibodies either under N 2 or under air by reducing the formation of perrhenate. High specific activity Re-188 labeled antibody is unstable, especially, in the presence of oxygen. Addition of vitamin C increased the stability

  14. A recombinant, fully human monoclonal antibody with antitumor activity constructed from phage-displayed antibody fragments

    NARCIS (Netherlands)

    Huls, GA; Heijnen, IAFM; Cuomo, ME; Koningsberger, JC; Boel, E; de Vries, ARV; Loyson, SAJ; Helfrich, W; Henegouwen, GPV; van Meijer, M; de Kruif, J; Logtenberg, T

    A single-chain Fv antibody fragment specific for the tumor-associated Ep-CAM molecule was isolated from a semisynthetic phage display library and converted into an intact, fully human IgG1 monoclonal antibody (huMab), The purified huMab had an affinity of 5 nM and effectively mediated tumor cell

  15. Higher cytotoxicity of divalent antibody-toxins than monovalent antibody-toxins

    International Nuclear Information System (INIS)

    Won, JaeSeon; Nam, PilWon; Lee, YongChan; Choe, MuHyeon

    2009-01-01

    Recombinant antibody-toxins are constructed via the fusion of a 'carcinoma-specific' antibody fragment to a toxin. Due to the high affinity and high selectivity of the antibody fragments, antibody-toxins can bind to surface antigens on cancer cells and kill them without harming normal cells [L.H. Pai, J.K. Batra, D.J. FitzGerald, M.C. Willingham, I. Pastan, Anti-tumor activities of immunotoxins made of monoclonal antibody B3 and various forms of Pseudomonas exotoxin, Proc. Natl. Acad. Sci. USA 88 (1991) 3358-3362]. In this study, we constructed the antibody-toxin, Fab-SWn-PE38, with SWn (n = 3, 6, 9) sequences containing n-time repeated (G 4 S) between the Fab fragment and PE38 (38 kDa truncated form of Pseudomonas exotoxin A). The SWn sequence also harbored one cysteine residue that could form a disulfide bridge between two Fab-SWn-PE38 monomers. We assessed the cytotoxicity of the monovalent (Fab-SWn-PE38), and divalent ([Fab-SWn-PE38] 2 ) antibody-toxins. The cytotoxicity of the dimer against the CRL1739 cell line was approximately 18.8-fold higher than that of the monomer on the ng/ml scale, which was approximately 37.6-fold higher on the pM scale. These results strongly indicate that divalency provides higher cytotoxicity for an antibody-toxin.

  16. Immunogenicity of anti-tumor necrosis factor antibodies - toward improved methods of anti-antibody measurement

    NARCIS (Netherlands)

    Aarden, Lucien; Ruuls, Sigrid R.; Wolbink, Gertjan

    2008-01-01

    To date, millions of people have been treated with therapeutic monoclonal antibodies (TmAbs) for various indications. It is becoming increasingly clear that TmAbs can be immunogenic, which may reduce efficacy or induce adverse effects. Over the years, the importance of antibody formation has been

  17. Thermodynamics of antibody-antigen interaction revealed by mutation analysis of antibody variable regions.

    Science.gov (United States)

    Akiba, Hiroki; Tsumoto, Kouhei

    2015-07-01

    Antibodies (immunoglobulins) bind specific molecules (i.e. antigens) with high affinity and specificity. In order to understand their mechanisms of recognition, interaction analysis based on thermodynamic and kinetic parameters, as well as structure determination is crucial. In this review, we focus on mutational analysis which gives information about the role of each amino acid residue in antibody-antigen interaction. Taking anti-hen egg lysozyme antibodies and several anti-small molecule antibodies, the energetic contribution of hot-spot and non-hot-spot residues is discussed in terms of thermodynamics. Here, thermodynamics of the contribution from aromatic, charged and hydrogen bond-forming amino acids are discussed, and their different characteristics have been elucidated. The information gives fundamental understanding of the antibody-antigen interaction. Furthermore, the consequences of antibody engineering are analysed from thermodynamic viewpoints: humanization to reduce immunogenicity and rational design to improve affinity. Amino acid residues outside hot-spots in the interface play important roles in these cases, and thus thermodynamic and kinetic parameters give much information about the antigen recognition. Thermodynamic analysis of mutant antibodies thus should lead to advanced strategies to design and select antibodies with high affinity. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  18. Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses.

    Science.gov (United States)

    Tay, Matthew Zirui; Liu, Pinghuang; Williams, LaTonya D; McRaven, Michael D; Sawant, Sheetal; Gurley, Thaddeus C; Xu, Thomas T; Dennison, S Moses; Liao, Hua-Xin; Chenine, Agnès-Laurence; Alam, S Munir; Moody, M Anthony; Hope, Thomas J; Haynes, Barton F; Tomaras, Georgia D

    2016-08-01

    Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine

  19. Antibody engineering using phage display with a coiled-coil heterodimeric Fv antibody fragment.

    Directory of Open Access Journals (Sweden)

    Xinwei Wang

    Full Text Available A Fab-like antibody binding unit, ccFv, in which a pair of heterodimeric coiled-coil domains was fused to V(H and V(L for Fv stabilization, was constructed for an anti-VEGF antibody. The anti-VEGF ccFv showed the same binding affinity as scFv but significantly improved stability and phage display level. Furthermore, phage display libraries in the ccFv format were constructed for humanization and affinity maturation of the anti-VEGF antibody. A panel of V(H frameworks and V(H-CDR3 variants, with a significant improvement in affinity and expressibility in both E. coli and yeast systems, was isolated from the ccFv phage libraries. These results demonstrate the potential application of the ccFv antibody format in antibody engineering.

  20. Kotai Antibody Builder: automated high-resolution structural modeling of antibodies.

    Science.gov (United States)

    Yamashita, Kazuo; Ikeda, Kazuyoshi; Amada, Karlou; Liang, Shide; Tsuchiya, Yuko; Nakamura, Haruki; Shirai, Hiroki; Standley, Daron M

    2014-11-15

    Kotai Antibody Builder is a Web service for tertiary structural modeling of antibody variable regions. It consists of three main steps: hybrid template selection by sequence alignment and canonical rules, 3D rendering of alignments and CDR-H3 loop modeling. For the last step, in addition to rule-based heuristics used to build the initial model, a refinement option is available that uses fragment assembly followed by knowledge-based scoring. Using targets from the Second Antibody Modeling Assessment, we demonstrate that Kotai Antibody Builder generates models with an overall accuracy equal to that of the best-performing semi-automated predictors using expert knowledge. Kotai Antibody Builder is available at http://kotaiab.org standley@ifrec.osaka-u.ac.jp. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Frequently relapsing anti-glomerular basement membrane antibody disease with changing clinical phenotype and antibody characteristics over time

    OpenAIRE

    Gu, Bobby; Magil, Alex B.; Barbour, Sean J.

    2016-01-01

    Anti-glomerular basement membrane (GBM) antibody disease is a typically monophasic autoimmune disease with severe pulmonary and renal involvement. We report an atypical case of frequently relapsing anti-GBM antibody disease with both anti-GBM antibody?positive flares with pulmonary and renal involvement, and anti-GBM antibody?negative flares that were pulmonary limited with no histologic renal disease. This is the first report of alternating disease phenotype and anti-GBM antibody status over...

  2. Identification of antibody glycosylation structures that predict monoclonal antibody Fc-effector function.

    Science.gov (United States)

    Chung, Amy W; Crispin, Max; Pritchard, Laura; Robinson, Hannah; Gorny, Miroslaw K; Yu, Xiaojie; Bailey-Kellogg, Chris; Ackerman, Margaret E; Scanlan, Chris; Zolla-Pazner, Susan; Alter, Galit

    2014-11-13

    To determine monoclonal antibody (mAb) features that predict fragment crystalizable (Fc)-mediated effector functions against HIV. Monoclonal antibodies, derived from Chinese hamster ovary cells or Epstein-Barr virus-immortalized mouse heteromyelomas, with specificity to key regions of the HIV envelope including gp120-V2, gp120-V3 loop, gp120-CD4(+) binding site, and gp41-specific antibodies, were functionally profiled to determine the relative contribution of the variable and constant domain features of the antibodies in driving robust Fc-effector functions. Each mAb was assayed for antibody-binding affinity to gp140(SR162), antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and for the ability to bind to FcγRIIa, FcγRIIb and FcγRIIIa receptors. Antibody glycan profiles were determined by HPLC. Neither the specificity nor the affinity of the mAbs determined the potency of Fc-effector function. FcγRIIIa binding strongly predicted ADCC and decreased galactose content inversely correlated with ADCP, whereas N-glycolylneuraminic acid-containing structures exhibited enhanced ADCP. Additionally, the bi-antenary glycan arm onto which galactose was added predicted enhanced binding to FcγRIIIa and ADCC activity, independent of the specificity of the mAb. Our studies point to the specific Fc-glycan structures that can selectively promote Fc-effector functions independently of the antibody specificity. Furthermore, we demonstrated antibody glycan structures associated with enhanced ADCP activity, an emerging Fc-effector function that may aid in the control and clearance of HIV infection.

  3. Imaging spectrum of primary antiphospholipid antibody syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Kwon Ha; Won, Jong Jin [Wonkwang University Hospital, Iksan (Korea, Republic of); Ha, Hyun Kwon; Kim, Jung Hoon; Kim, Jeong Gon; Ki, Won Woo; Kim, Pyo Nyun; Lee, Moon Gyu; Auh, Yong Ho [Asan Medical Center, Seoul (Korea, Republic of)

    1998-04-01

    Antiphospholipid antibody syndrome is recognized as one of the most important causes of hypercoagulability. It can be clinically diagnosed if patients have experienced unexplained recurrent venous or arterial thrombosis, recurrent fetal loss, or thrombocytopenia in the presence of circulating autoantibodies to phospholipids, such as anticardiolipin antibody or lupus anticoagulant. Approximately half of all patients with this syndrome do not have associated systemic disease, and their condition is described as primary antiphospholipid antibody syndrome (PAPS). In the remainder, the syndrome is accompanied by systemic lupus erythematosus or other connective tissue diseases, and is known as secondary antiphospholipid syndrome (1). The purpose of this paper is to illustrate the systemic manifestation of PAPS, focusing on the radiological findings of CT, MR and angiography in clinically proven patients. (author). 8 refs., 10 figs.

  4. Quantitative imaging with radiolabeled monoclonal antibodies

    International Nuclear Information System (INIS)

    Moldofsky, P.J.; Hammond, N.D.

    1988-01-01

    The ability to image tumor by using radiolabeled monoclonal antibody products has been widely demonstrated. The questions of safety and efficacy remain open and require further experience, but at least in some clinical situations radioimmunoimaging has provided clinically useful information. Imaging tumor with radiolabeled monoclonal and polyclonal antibodies has been widely reported, and several summaries have recently appeared. For extensive review of recent clinical imaging the reader is referred to these excellent sources. Having demonstrated the possibility of imaging tumor with radiolabeled antibody, the question now apparent is: will the imaging modality provide information new and different from the already available with established techniques in computed tomography, magnetic resonance imaging, and standard nuclear medicine?

  5. Origin and pathogenesis of antiphospholipid antibodies

    Directory of Open Access Journals (Sweden)

    C.M. Celli

    1998-06-01

    Full Text Available Antiphospholipid antibodies (aPL are a heterogeneous group of antibodies that are detected in the serum of patients with a variety of conditions, including autoimmune (systemic lupus erythematosus, infectious (syphilis, AIDS and lymphoproliferative disorders (paraproteinemia, myeloma, lymphocytic leukemias. Thrombosis, thrombocytopenia, recurrent fetal loss and other clinical complications are currently associated with a subgroup of aPL designating the antiphospholipid syndrome. In contrast, aPL from patients with infectious disorders are not associated with any clinical manifestation. These findings led to increased interest in the origin and pathogenesis of aPL. Here we present the clinical features of the antiphospholipid syndrome and review the origin of aPL, the characteristics of experimentally induced aPL and their historical background. Within this context, we discuss the most probable pathogenic mechanisms induced by these antibodies.

  6. Imaging spectrum of primary antiphospholipid antibody syndrome

    International Nuclear Information System (INIS)

    Yoon, Kwon Ha; Won, Jong Jin; Ha, Hyun Kwon; Kim, Jung Hoon; Kim, Jeong Gon; Ki, Won Woo; Kim, Pyo Nyun; Lee, Moon Gyu; Auh, Yong Ho

    1998-01-01

    Antiphospholipid antibody syndrome is recognized as one of the most important causes of hypercoagulability. It can be clinically diagnosed if patients have experienced unexplained recurrent venous or arterial thrombosis, recurrent fetal loss, or thrombocytopenia in the presence of circulating autoantibodies to phospholipids, such as anticardiolipin antibody or lupus anticoagulant. Approximately half of all patients with this syndrome do not have associated systemic disease, and their condition is described as primary antiphospholipid antibody syndrome (PAPS). In the remainder, the syndrome is accompanied by systemic lupus erythematosus or other connective tissue diseases, and is known as secondary antiphospholipid syndrome (1). The purpose of this paper is to illustrate the systemic manifestation of PAPS, focusing on the radiological findings of CT, MR and angiography in clinically proven patients. (author). 8 refs., 10 figs

  7. Characterization of monoclonal antibodies directed against human thyroid stimulating hormone

    International Nuclear Information System (INIS)

    Soos, M.; Siddle, K.

    1982-01-01

    Monoclonal antibodies directed against human thyroid stimulating hormone (TSH) were obtained from hybrid myelomas, following fusion of mouse NSI myeloma cells with mouse spleen cells. Ten different antibodies were obtained from 4 separate fusions. Eight antibodies were of the IgG 1 subclass. Affinities of antibodies for TSH were in the range 2 x 10 8 -5 x 10 10 M -1 . Five of the antibodies were specific for TSH and did not react with LH, FSH or hCG. The remaining antibodies reacted with all these hormones and were assumed to recognise their common (α) subunit. The 5 specific antibodies fell into 3 subgroups recognising distinct antigenic determinants, whereas the 5 non-specific antibodies recognised a single determinant or closely related set of sites. It is concluded that these antibodies should be valuable reagents for use in sensitive and specific two-site immunoradiometric assays. (Auth.)

  8. Ultrastructural visualization of the transmembranous and cytomatrix-related part of nicotinic acetylcholine receptor of frog motor endplate by means of an immunochemical avidity of IgG for d-tubocurarine.

    Directory of Open Access Journals (Sweden)

    Shigeru Tsuji

    2008-02-01

    Full Text Available In the present study, a fine ultrastructural localization of nicotinic acetylcholine receptor (nAChR was attempted, using d-tubocurarine (d-TC, a quaternary ammonium compound binding to nAChR. The localization was based on the binding avidity of immunoglobulin G (IgG for acetylcholine (ACh and other quaternary ammonium compounds, such as d-TC. d-TC was applied to the frog neuromuscular preparation and caused a blockade of neuromuscular transmission. Then, d-TC was rendered insoluble in situ by silicotungstic acid (STA, a precipitating agent of soluble proteins and quaternary ammonium compounds. After tissue fixation, a normal rabbit serum was applied to the fine precipitate of the insoluble salt of d-TC silicotungstate (quaternary ammonium radical of d-TC to form the immunochemical complex d-TC- rabbit IgG at ACh binding sites. The IgG of the complex was revealed by means of the conventional immunoperoxidase procedure used for ultrastructural localization. Under the electron microscope, fine diaminobenzidine (DAB precipitates appeared as regular rod-like structures oriented to cytoplasmic side of the horizontal part (crest of the postsynaptic membrane (between the junctional folds which is known to be endowed with nAChR. The rod-like precipitates were not observed in the postsynaptic junctional folds which are devoid of nAChR. The distance separating the rods each other was rather constant (12 - 15 nm, while the length of the rods was variable and exceeded the usual length of nAChR. The present work indicates that the rod-like structures, already observed in association with sarcoplasmic side of the postsynaptic membrane, did correspond to the intramembranous and intracytoplasmic part of nAChR and related proteins. These cytochemical results confirm that d-TC binds to ACh binding sites in the pore of nAChR, and raise the question of DAB staining of cytoskeletal proteins related to the nAChR complex.

  9. Multiplex serology of paraneoplastic antineuronal antibodies.

    Science.gov (United States)

    Maat, Peter; Brouwer, Eric; Hulsenboom, Esther; VanDuijn, Martijn; Schreurs, Marco W J; Hooijkaas, Herbert; Smitt, Peter A E Sillevis

    2013-05-31

    Paraneoplastic neurological syndromes (PNS) are devastating neurological disorders secondary to cancer, associated with onconeural autoantibodies. Such antibodies are directed against neuronal antigens aberrantly expressed by the tumor. The detection of onconeural antibodies in a patient is extremely important in diagnosing a neurological syndrome as paraneoplastic (70% is not yet known to have cancer) and in directing the search for the underlying neoplasm. At present six onconeural antibodies are considered 'well characterized' and recognize the antigens HuD, CDR62 (Yo), amphiphysin, CRMP-5 (CV2), NOVA-1 (Ri), and Ma2. The gold standard of detection is the characteristic immunohistochemical staining pattern on brain tissue sections combined with confirmation by immunoblotting using recombinant purified proteins. Since all six onconeural antibodies are usually analyzed simultaneously and objective cut-off values for these analyses are warranted, we developed a multiplex assay based on Luminex technology. Reaction of serial dilutions of six onconeural standard sera with microsphere-bound antigens showed lower limits of detection than with Western blotting. Using the six standard sera at a dilution of 1:200, the average within-run coefficient of variation (CV) was 4% (range 1.9-7.3%). The average between-run within-day CV was 5.1% (range 2.9-6.7%) while the average between-day CV was 8.1% (range 2.8-11.6%). The shelf-life of the antigen coupled microspheres was at least two months. The sensitivity of the multiplex assay ranged from 83% (Ri) to 100% (Yo, amphiphysin, CV2) and the specificity from 96% (CV2) to 100% (Ri). In conclusion, Luminex-based multiplex serology is highly reproducible with high sensitivity and specificity for the detection of onconeural antibodies. Conventional immunoblotting for diagnosis of onconeural antibodies in the setting of a routine laboratory may be replaced by this novel, robust technology. Copyright © 2013 Elsevier B.V. All rights

  10. Quantitative cumulative biodistribution of antibodies in mice

    Science.gov (United States)

    Yip, Victor; Palma, Enzo; Tesar, Devin B; Mundo, Eduardo E; Bumbaca, Daniela; Torres, Elizabeth K; Reyes, Noe A; Shen, Ben Q; Fielder, Paul J; Prabhu, Saileta; Khawli, Leslie A; Boswell, C Andrew

    2014-01-01

    The neonatal Fc receptor (FcRn) plays an important and well-known role in antibody recycling in endothelial and hematopoietic cells and thus it influences the systemic pharmacokinetics (PK) of immunoglobulin G (IgG). However, considerably less is known about FcRn’s role in the metabolism of IgG within individual tissues after intravenous administration. To elucidate the organ distribution and gain insight into the metabolism of humanized IgG1 antibodies with different binding affinities FcRn, comparative biodistribution studies in normal CD-1 mice were conducted. Here, we generated variants of herpes simplex virus glycoprotein D-specific antibody (humanized anti-gD) with increased and decreased FcRn binding affinity by genetic engineering without affecting antigen specificity. These antibodies were expressed in Chinese hamster ovary cell lines, purified and paired radiolabeled with iodine-125 and indium-111. Equal amounts of I-125-labeled and In-111-labeled antibodies were mixed and intravenously administered into mice at 5 mg/kg. This approach allowed us to measure both the real-time IgG uptake (I-125) and cumulative uptake of IgG and catabolites (In-111) in individual tissues up to 1 week post-injection. The PK and distribution of the wild-type IgG and the variant with enhanced binding for FcRn were largely similar to each other, but vastly different for the rapidly cleared low-FcRn-binding variant. Uptake in individual tissues varied across time, FcRn binding affinity, and radiolabeling method. The liver and spleen emerged as the most concentrated sites of IgG catabolism in the absence of FcRn protection. These data provide an increased understanding of FcRn’s role in antibody PK and catabolism at the tissue level. PMID:24572100

  11. Advanced Visualization and Interactive Displays (AVID)

    Science.gov (United States)

    2009-04-01

    decision maker. The ACESViewer architecture allows the users to pull data from databases, flat files, or user generated via scripting. The...of the equation and is of critical concern as it scales the needs of the polygon fill operations. Numerous users are now using two 30” cinema ...6 module configuration. Based on the architecture of the lab there was only one location that would be suitable without any viewing obstructions

  12. Nuclear oncology with monoclonal antibodies and peptides

    International Nuclear Information System (INIS)

    Hosono, Makoto

    1998-01-01

    Imaging and therapy using radiolabeled monoclonal antibodies have proved useful in many clinical studies. However, immunogenicity of mouse antibodies to human and insufficient tumor-to-normal tissue ratios remained to be solved. Chimerization and humanization by genetic engineering, and multistep targeting techniques have enabled lower immunogenicity and higher tumor-to-normal tissue contrast. Peptides like somatostatin-analogs have been reportedly useful in imaging tumors, which are either somatostatin receptor positive or negative. Elevated normal tissue accumulation of radiolabeled peptides is a drawback in aiming internal radiation therapy. (author). 51 refs

  13. Beyond Antibodies as Binding Partners: The Role of Antibody Mimetics in Bioanalysis.

    Science.gov (United States)

    Yu, Xiaowen; Yang, Yu-Ping; Dikici, Emre; Deo, Sapna K; Daunert, Sylvia

    2017-06-12

    The emergence of novel binding proteins or antibody mimetics capable of binding to ligand analytes in a manner analogous to that of the antigen-antibody interaction has spurred increased interest in the biotechnology and bioanalytical communities. The goal is to produce antibody mimetics designed to outperform antibodies with regard to binding affinities, cellular and tumor penetration, large-scale production, and temperature and pH stability. The generation of antibody mimetics with tailored characteristics involves the identification of a naturally occurring protein scaffold as a template that binds to a desired ligand. This scaffold is then engineered to create a superior binder by first creating a library that is then subjected to a series of selection steps. Antibody mimetics have been successfully used in the development of binding assays for the detection of analytes in biological samples, as well as in separation methods, cancer therapy, targeted drug delivery, and in vivo imaging. This review describes recent advances in the field of antibody mimetics and their applications in bioanalytical chemistry, specifically in diagnostics and other analytical methods.

  14. Anti-transferrin receptor antibody and antibody-drug conjugates cross the blood-brain barrier

    International Nuclear Information System (INIS)

    Friden, P.M.; Walus, L.R.; Musso, G.F.; Taylor, M.A.; Malfroy, B.; Starzyk, R.M.

    1991-01-01

    Delivery of nonlipophilic drugs to the brain is hindered by the tightly apposed capillary endothelial cells that make up the blood-brain barrier. The authors have examined the ability of a monoclonal antibody (OX-26), which recognizes the rat transferrin receptor, to function as a carrier for the delivery of drugs across the blood-brain barrier. This antibody, which was previously shown to bind preferentially to capillary endothelial cells in the brain after intravenous administration, labels the entire cerebrovascular bed in a dose-dependent manner. The initially uniform labeling of brain capillaries becomes extremely punctate ∼ 4 hr after injection, suggesting a time-dependent sequestering of the antibody. Capillary-depletion experiments, in which the brain is separated into capillary and parenchymal fractions, show a time-dependent migration of radiolabeled antibody from the capillaries into the brain parenchyma, which is consistent with the transcytosis of compounds across the blood-brain barrier. Antibody-methotrexate conjugates were tested in vivo to assess the carrier ability of this antibody. Immunohistochemical staining for either component of an OX-26-methotrexate conjugate revealed patterns of cerebrovascular labeling identical to those observed with the unaltered antibody. Accumulation of radiolabeled methotrexate in the brain parenchyma is greatly enhanced when the drug is conjugated to OX-26

  15. VHH Antibodies: Reagents for Mycotoxin Detection in Food Products

    Directory of Open Access Journals (Sweden)

    Jia Wang

    2018-02-01

    Full Text Available Mycotoxins are the toxic secondary metabolites produced by fungi and they are a worldwide public health concern. A VHH antibody (or nanobody is the smallest antigen binding entity and is produced by heavy chain only antibodies. Compared with conventional antibodies, VHH antibodies overcome many pitfalls typically encountered in clinical therapeutics and immunodiagnostics. Likewise, VHH antibodies are particularly useful for monitoring mycotoxins in food and feedstuffs, as they are easily genetic engineered and have superior stability. In this review, we summarize the efforts to produce anti-mycotoxins VHH antibodies and associated assays, presenting VHH as a potential tool in mycotoxin analysis.

  16. Impact of Uniform Methods on Interlaboratory Antibody Titration Variability: Antibody Titration and Uniform Methods.

    Science.gov (United States)

    Bachegowda, Lohith S; Cheng, Yan H; Long, Thomas; Shaz, Beth H

    2017-01-01

    -Substantial variability between different antibody titration methods prompted development and introduction of uniform methods in 2008. -To determine whether uniform methods consistently decrease interlaboratory variation in proficiency testing. -Proficiency testing data for antibody titration between 2009 and 2013 were obtained from the College of American Pathologists. Each laboratory was supplied plasma and red cells to determine anti-A and anti-D antibody titers by their standard method: gel or tube by uniform or other methods at different testing phases (immediate spin and/or room temperature [anti-A], and/or anti-human globulin [AHG: anti-A and anti-D]) with different additives. Interlaboratory variations were compared by analyzing the distribution of titer results by method and phase. -A median of 574 and 1100 responses were reported for anti-A and anti-D antibody titers, respectively, during a 5-year period. The 3 most frequent (median) methods performed for anti-A antibody were uniform tube room temperature (147.5; range, 119-159), uniform tube AHG (143.5; range, 134-150), and other tube AHG (97; range, 82-116); for anti-D antibody, the methods were other tube (451; range, 431-465), uniform tube (404; range, 382-462), and uniform gel (137; range, 121-153). Of the larger reported methods, uniform gel AHG phase for anti-A and anti-D antibodies had the most participants with the same result (mode). For anti-A antibody, 0 of 8 (uniform versus other tube room temperature) and 1 of 8 (uniform versus other tube AHG), and for anti-D antibody, 0 of 8 (uniform versus other tube) and 0 of 8 (uniform versus other gel) proficiency tests showed significant titer variability reduction. -Uniform methods harmonize laboratory techniques but rarely reduce interlaboratory titer variance in comparison with other methods.

  17. Efficient generation of monoclonal antibodies from single rhesus macaque antibody secreting cells.

    Science.gov (United States)

    Meng, Weixu; Li, Leike; Xiong, Wei; Fan, Xuejun; Deng, Hui; Bett, Andrew J; Chen, Zhifeng; Tang, Aimin; Cox, Kara S; Joyce, Joseph G; Freed, Daniel C; Thoryk, Elizabeth; Fu, Tong-Ming; Casimiro, Danilo R; Zhang, Ningyan; A Vora, Kalpit; An, Zhiqiang

    2015-01-01

    Nonhuman primates (NHPs) are used as a preclinical model for vaccine development, and the antibody profiles to experimental vaccines in NHPs can provide critical information for both vaccine design and translation to clinical efficacy. However, an efficient protocol for generating monoclonal antibodies from single antibody secreting cells of NHPs is currently lacking. In this study we established a robust protocol for cloning immunoglobulin (IG) variable domain genes from single rhesus macaque (Macaca mulatta) antibody secreting cells. A sorting strategy was developed using a panel of molecular markers (CD3, CD19, CD20, surface IgG, intracellular IgG, CD27, Ki67 and CD38) to identify the kinetics of B cell response after vaccination. Specific primers for the rhesus macaque IG genes were designed and validated using cDNA isolated from macaque peripheral blood mononuclear cells. Cloning efficiency was averaged at 90% for variable heavy (VH) and light (VL) domains, and 78.5% of the clones (n = 335) were matched VH and VL pairs. Sequence analysis revealed that diverse IGHV subgroups (for VH) and IGKV and IGLV subgroups (for VL) were represented in the cloned antibodies. The protocol was tested in a study using an experimental dengue vaccine candidate. About 26.6% of the monoclonal antibodies cloned from the vaccinated rhesus macaques react with the dengue vaccine antigens. These results validate the protocol for cloning monoclonal antibodies in response to vaccination from single macaque antibody secreting cells, which have general applicability for determining monoclonal antibody profiles in response to other immunogens or vaccine studies of interest in NHPs.

  18. Antimitochondrial antibodies and other antibodies in primary biliary cirrhosis: diagnostic and prognostic value.

    Science.gov (United States)

    Muratori, Luigi; Granito, Alessandro; Muratori, Paolo; Pappas, Georgios; Bianchi, Francesco B

    2008-05-01

    Antimitochondrial antibodies (AMA) are the serologic cornerstone in the diagnosis of primary biliary cirrhosis (PBC), even if they are not detectable in a proportion of patients, notwithstanding the most sensitive and sophisticated technologies used. To fill in the serologic gap in AMA-negative PBC, there is sound evidence to consider antinuclear antibody (ANA) patterns, such as anti-multiple nuclear dots and anti-membranous/rim-like, as PBC-specific surrogate hallmarks of the disease, and their detection can be considered virtually diagnostic. Furthermore, particular ANA specificities, such as anti-gp210, anti-p62, anticentromere antibodies, and anti-dsDNA, may provide additional diagnostic and prognostic information.

  19. Radioimmunodetection of tumor with Ga-67 labeled antibodies

    International Nuclear Information System (INIS)

    Furukawa, Takako; Endo, Keigo; Ohmomo, Yoshiro

    1986-01-01

    Antibodies against tumor associated antigen; anti-AFP polyclonal antibody, anti-thyroglobulin monoclonal antibody and anti-hCG monoclonal antibody, were labeled with Ga-67, using deferoxamine (DF) as a bifunctional chelating agent. The immunoreactivity and in vivo stability of the Ga-67 labeled antibodies were examined. The effect of DF conjugation to antibodies on the antigen-binding activity was evaluated by RIA and Scatchard analysis or tanned sheep red blood cell hemagglutination technique. When DF was conjugated to antibody at the molar ratio of 1 : 1, the antibody activity of the DF-conjugated antibodies was fully retained. Whereas, in heavily conjugated antibodies, the maximum antigen binding capacity was reduced. Biodistribution study in normal mice demonstrated the high in vivo stability of Ga-67 labeled antibodies. The labeling of DF-antibody conjugated with Ga-67 was performed easily and quickly, with a high labeling efficiency, requiring no further purification. Thus, this labeling method, providing in vivo stability of Ga-67 labeled antibody and full retention of immunoreactivity, would be useful for the radioimmunodetection of various cancers. (author)

  20. Aggregates in monoclonal antibody manufacturing processes.

    Science.gov (United States)

    Vázquez-Rey, María; Lang, Dietmar A

    2011-07-01

    Monoclonal antibodies have proved to be a highly successful class of therapeutic products. Large-scale manufacturing of pharmaceutical antibodies is a complex activity that requires considerable effort in both process and analytical development. If a therapeutic protein cannot be stabilized adequately, it will lose partially or totally its therapeutic properties or even cause immunogenic reactions thus potentially further endangering the patients' health. The phenomenon of protein aggregation is a common issue that compromises the quality, safety, and efficacy of antibodies and can happen at different steps of the manufacturing process, including fermentation, purification, final formulation, and storage. Aggregate levels in drug substance and final drug product are a key factor when assessing quality attributes of the molecule, since aggregation might impact biological activity of the biopharmaceutical. In this review it is analyzed how aggregates are formed during monoclonal antibody industrial production, why they have to be removed and the manufacturing process steps that are designed to either minimize or remove aggregates in the final product. Copyright © 2011 Wiley Periodicals, Inc.

  1. Antibody orientation on biosensor surfaces: a minireview

    NARCIS (Netherlands)

    Trilling, A.K.; Beekwilder, M.J.; Zuilhof, H.

    2013-01-01

    Detection elements play a key role in analyte recognition in biosensors. Therefore, detection elements with high analyte specificity and binding strength are required. While antibodies (Abs) have been increasingly used as detection elements in biosensors, a key challenge remains – the immobilization

  2. Strain differentiation of polioviruses with monoclonal antibodies.

    NARCIS (Netherlands)

    A.D.M.E. Osterhaus (Albert); A.L. van Wezel; A.J.H. Stegmann; J.A.A.M. van Asten (Jack)

    1984-01-01

    textabstractPanels of monoclonal antibodies raised against different poliovirus type 1, 2 and 3 strains, were tested in a micro-neutralization test and in a micro-enzyme linked immunosorbent assay against a large number of poliovirus strains. The results were compared with those obtained with the

  3. Comparisons of the effect of naturally acquired maternal pertussis antibodies and antenatal vaccination induced maternal tetanus antibodies on infant's antibody secreting lymphocyte responses and circulating plasma antibody

    Science.gov (United States)

    The goal of this study was to explore the effects of trans-placental tetanus toxoid (TT) and pertussis (PT) antibodies on an infant's response to vaccination in the context of antenatal immunization with tetanus but not with pertussis. 38 mothers received a single dose of TT vaccine during pregnancy...

  4. The prevalence ofantiphospholipid antibodies in women with ...

    African Journals Online (AJOL)

    patients. PTT, APTT, kaolin clotting time (KCT),. Russell viper venom time CRvvn were measured in all the subjects, who were also assessed for the presence of anticardiolipin antibodies. Blood was taken by venepuncture into a 0,1 volume of 3,8% trisodium citrate. Platelet-rich plasma (PRP) was prepared by centrifuging of ...

  5. Seroprevalence of hepatitis C antibody in Peru.

    Science.gov (United States)

    Hyams, K C; Phillips, I A; Moran, A Y; Tejada, A; Wignall, F S; Escamilla, J

    1992-06-01

    The prevalence in Peru of antibody to hepatitis C virus (anti-HCV) was determined in a survey of populations living in the northern jungle region and in groups at high risk of parenterally and sexually transmitted diseases. All sera were initially screened for anti-HCV using commercial first and second generation ELISAs; repeatedly reactive sera were further verified with a second generation immunoblot assay. Serum samples were also tested by ELISA for HBsAg, anti-HBs, and anti-HBc. None of 2,111 sera obtained in the survey of jungle residents was positive for anti-HCV by immunoblot assay. Twelve of 16 HIV-1 antibody positive hemophiliacs, one of 103 HIV-1 antibody positive homosexuals, and three of 602 HIV-1 negative registered female prostitutes were positive for anti-HCV. A high prevalence of total markers of hepatitis B infection was found in all subjects, especially in older subjects and groups at high risk of parenterally and sexually transmitted diseases. The findings of this study indicate that seropositivity for hepatitis C virus antibody is uncommon in Peru except in high risk groups and suggest that the epidemiology of hepatitis C differs substantially from hepatitis B.

  6. Research Paper Polyclonal antibodies production against ...

    African Journals Online (AJOL)

    The main aim of this project is to produce polyclonal antibodies directed against the Staphylococcus aureus protein A and their use to appreciate bacteriological analysis of milk quality. In this context, an immunization produce was set up to test and detect in a batch of animals the convenient responder to the injected ...

  7. Monoclonal antibody technologies and rapid detection assays

    Science.gov (United States)

    Novel methodologies and screening strategies will be outlined on the use of hybridoma technology for the selection of antigen specific monoclonal antibodies. The development of immunoassays used for diagnostic detection of prions and bacterial toxins will be discussed and examples provided demonstr...

  8. Monoclonal antibody therapy of inflammatory bowel disease

    NARCIS (Netherlands)

    van Deventer, S. J.; Camoglio, L.

    1996-01-01

    Several anti-inflammatory drugs have therapeutic efficacy in inflammatory bowel disease, but their targets remain incompletely characterized. The development of monoclonal antibodies that either recognize epitopes on immune-competent cells, or neutralize pro-inflammatory cytokines, has helped to

  9. Immunosignature: Serum Antibody Profiling for Cancer Diagnostics.

    Science.gov (United States)

    Chapoval, Andrei I; Legutki, J Bart; Stafford, Philip; Trebukhov, Andrey V; Johnston, Stephen A; Shoikhet, Yakov N; Lazarev, Alexander F

    2015-01-01

    Biomarkers for preclinical diagnosis of cancer are valuable tools for detection of malignant tumors at early stages in groups at risk and screening healthy people, as well as monitoring disease recurrence after treatment of cancer. However the complexity of the body's response to the pathological processes makes it virtually impossible to evaluate this response to the development of the disease using a single biomarker that is present in the serum at low concentrations. An alternative approach to standard biomarker analysis is called immunosignature. Instead of going after biomarkers themselves this approach rely on the analysis of the humoral immune response to molecular changes associated with the development of pathological processes. It is known that antibodies are produced in response to proteins expressed during cancer development. Accordingly, the changes in antibody repertoire associated with tumor growth can serve as biomarkers of cancer. Immunosignature is a highly sensitive method for antibody repertoire analysis utilizing high density peptide microarrays. In the present review we discuss modern methods for antibody detection, as well as describe the principles and applications of immunosignature in research and clinical practice.

  10. Radioimmunoimaging of tumors with a pantumor antibody

    International Nuclear Information System (INIS)

    Chen, D.C.P.; Siegel, M.E.; Chen, F.; Taylor, O.R.; Epstein, A.L.

    1988-01-01

    The TNT-1 antibody was developed to bind intracellular nuclear antigens that are accessible only in degenerative or necrotic cells. Since about 50% of tumor cells are in various stages of cell degeneration or death, this antibody could serve as a pantumor antibody for tumor detection. After intravenous injection of 10 μg of TNT-1F(ab')2 fragments labeled with 20 μCi of I-131, serial images were obtained at 1 and 4 hours and daily for 6 days in mice bearing various human tumors. Accumulation of TNT-1 was imaged in a necrotic tumor as early as 4 hours after injection and because more intense at 48 hours. The tumor-muscle ratio was as high as 29:1. Intense accumulation was noted in the necrotic tumor, about nine times that of healthy tumor. In conclusion, TNT-1, a pantumor antibody, can detect necrotic tumors in animal models. It may be an ideal imaging agent for cancer detection

  11. Bone marrow dosimetry for monoclonal antibody therapy

    International Nuclear Information System (INIS)

    Bigler, R.E.; Zanzonico, P.B.; Leonard, R.

    1986-01-01

    Immunoglobulins must permeate through the basement membrane of capillaries in order to enter the extracellular space (ECS) of tissue. Since the process is quite slow, the blood plasma activity in various organs contributes considerably to the radiation dose of the dose-limiting tissues. In bone marrow the basement membrane is absent and the blood circulation is functionally open. Therefore, blood plasma and marrow ECS maintain equal concentrations of labeled immunoglobulins. A combination of factors including intravenous administration, slow absorption into most tissues, slow breakdown and elimination of labeled immunoglobulin, and rapid entry into bone marrow ECS as well as known radiosensitivity of marrow led the authors to expect this tissue would prove to be the primary tissue at risk for systemic monoclonal antibody therapy. They have developed and applied in a Phase I clinical study of 131 I labeled CEA antibody a procedure for estimation of radiation dose to red bone marrow. Serieal measurements of blood plasma and total body retention are carried out. Binding of labeled antibody to the cellular components of blood is verified to be very low. They have observed bone marrow depression at doses greater than 400 rad. If no special procedures are used to reconstitute marrow after radiation treatment, this level represents a much greater than generally recognized limitation to radiolabeled monoclonal antibody therapy. 25 references, 4 tables

  12. antibodies against Herpes simplex virus (HSV)

    African Journals Online (AJOL)

    Chi-square analysis was used to determine the association of infection with ... tibody. No statistical association existed between the prevalence of HSV-1&-2 IgG antibodies and the socio-demographic variables ... concern, established by the widespread of genital HSV .... Chi-square test was employed to define relationships.

  13. Antiphospholipid Antibody Syndrome Presenting with Hemichorea

    Directory of Open Access Journals (Sweden)

    Yezenash Ayalew

    2012-01-01

    Full Text Available A 25-year-old Bangladeshi lady presented to neurology with a three-month history of involuntary movements of her right arm, associated with loss of power. There was progression to the right leg, and she subsequently developed episodes of slurred speech and blurred vision. At the time of presentation, she was 12 weeks pregnant and the symptoms were reported to have started at conception. Past medical history was unremarkable apart from one first trimester miscarriage and there was no significant family history suggestive of a hereditary neurological condition. MRI of the head revealed no abnormalities but serology showed positive antinuclear antibodies (ANAs at a titre of 1/400. Further investigations revealed strongly positive anticardiolipin antibodies (>120 and positive lupus anticoagulant antibodies. The patient had a second miscarriage at 19 weeks gestation strengthening the possibility that the chorea was related to antiphospholipid antibody syndrome and she was started on a reducing dose of Prednisolone 40 mg daily and aspirin 300 mg daily. Six months later, she had complete resolution of neurological symptoms. There are several reports of chorea as a feature of antiphospholipid syndrome, but no clear consensus on underlying pathophysiology.

  14. Onconeural Antibodies in Acute Psychiatric Inpatient Care

    DEFF Research Database (Denmark)

    Sæther, Sverre Georg; Schou, Morten; Stoecker, Winfried

    2017-01-01

    , GLRA1B, DPPX, GRM1, GRM5, DNER, Yo, ZIC4, GAD67, amphiphysin, CV2, Hu, Ri, Ma2, and recoverin. Only one sample was positive (antirecoverin IgG). The present findings suggest that serum onconeural antibody positivity is rare among patients acutely admitted for inpatient psychiatric care. The clinical...

  15. Human immunodeficiency virus (HIV) specific antibodies among ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-03-20

    Mar 20, 2009 ... Key words: HIV-1/2 antibody prevalence, pregnant women, commercial sex workers, risk factors, Nigeria. INTRODUCTION. There are two .... Africa. However, among Japanese and Chilean female. SWs, Miyazaki et al. .... STIs (P = 0.0001, OR = 6.0), level of education (P = 0.0001, OR = 40.7) and age (P ...

  16. [Antibodies and physiopathogeny of autoimmune hepatitis].

    Science.gov (United States)

    García-Leiva, Jorge; Ríos-Vaca, Aurelio; Torre-Delgadillo, Aldo

    2003-01-01

    Autoimmune hepatitis (AIH) is an inflammatory disease of unknown cause characterized by periportal hepatitis, increased serum globulins and the presence of certain antibodies. The disorder can be classified in three types. Type 1 AIH is characterized by the presence of antinuclear antibodies (ANA) and smooth muscle autoantibodies (SMA) in up to 70-80% of patients. ANA and SMA can be the only antibodies present in 13 and 33% of cases respectively. Type 2 AIH is defined by the presence of liver and kidney antimicrosomal antibodies (LKM1). Type 2 AIH is the only form of the disease in which the autoantigen has been identified: cytochrome mono-oxygenase (P-450 IID6) CYP2D6. In type 3 AIH the presence of anti-SLA/LP (soluble liver antigen/liver pancreas) targets a cytosolic protein involved in the incorporation of selenocysteine into peptidic chains. The pathophysiology of AIH is complex and involves genetic predisposition, previous exposure to antigens (autoantigens), presence of triggering factors and defects in immunoregulation. In spite of the advances in the understanding of AIH, the role of autoantibodies in the pathophysiology of this disease has not been fully established and their presence does not clearly distinguish any prognostic groups. Further investigations will help in the diagnosis of this disorder, the comprehension of its origins and the establishment of new forms of treatment.

  17. Polyclonal antibodies of Ganoderma boninense isolated from ...

    African Journals Online (AJOL)

    Polyclonal antibodies of Ganoderma boninense isolated from Malaysian oil palm for detection of basal stem rot disease. ... ELISA-PAb shows better detection as compared to cultural-based method, Ganoderma selective medium (GSM) with an improvement of 18% at nursery trial. The present study also demonstrates ...

  18. Burkholderia pseudomallei Antibodies in Children, Cambodia

    Science.gov (United States)

    Pheaktra, Ngoun; Putchhat, Hor; Sin, Lina; Sen, Bun; Kumar, Varun; Langla, Sayan; Peacock, Sharon J.; Day, Nicholas P.

    2008-01-01

    Antibodies to Burkholderia pseudomallei were detected in 16% of children in Siem Reap, Cambodia. This organism was isolated from 30% of rice paddies in the surrounding vicinity. Despite the lack of reported indigenous cases, melioidosis is likely to occur in Cambodia. PMID:18258125

  19. Antibodies to actin in autoimmune haemolytic anaemia

    Directory of Open Access Journals (Sweden)

    Ritzmann Mathias

    2010-03-01

    Full Text Available Abstract Background In autoimmune haemolytic anaemia (AIHA, autoreactive antibodies directed against red blood cells are up-regulated, leading to erythrocyte death. Mycoplasma suis infections in pigs induce AIHA of both the warm and cold types. The aim of this study was to identify the target autoantigens of warm autoreactive IgG antibodies. Sera from experimentally M. suis-infected pigs were screened for autoreactivity. Results Actin-reactive antibodies were found in the sera of 95% of all animals tested. The reactivity was species-specific, i.e. reactivity with porcine actin was significantly higher than with rabbit actin. Sera of animals previously immunised with the M. suis adhesion protein MSG1 showed reactivity with actin prior to infection with M. suis indicating that molecular mimicry is involved in the specific autoreactive mechanism. A potentially cross-reactive epitope was detected. Conclusions This is the first report of autoreactive anti-actin antibodies involved in the pathogenesis of autoimmune haemolytic anaemia.

  20. Neuronal surface antigen antibodies in limbic encephalitis

    Science.gov (United States)

    Graus, F; Saiz, A; Lai, M; Bruna, J; López, F; Sabater, L; Blanco, Y; Rey, M J.; Ribalta, T; Dalmau, J

    2008-01-01

    Objective: To report the frequency and type of antibodies against neuronal surface antigens (NSA-ab) in limbic encephalitis (LE). Methods: Analysis of clinical features, neuropathologic findings, and detection of NSA-ab using immunochemistry on rat tissue and neuronal cultures in a series of 45 patients with paraneoplastic (23) or idiopathic (22) LE. Results: NSA-ab were identified in 29 patients (64%; 12 paraneoplastic, 17 idiopathic). Thirteen patients had voltage-gated potassium channels (VGKC)-ab, 11 novel NSA (nNSA)-ab, and 5 NMDA receptor (NMDAR)-ab. nNSA-ab did not identify a common antigen and were more frequent in paraneoplastic than idiopathic LE (39% vs 9%; p = 0.03). When compared with VGKC-ab or NMDAR-ab, the nNSA associated more frequently with intraneuronal antibodies (11% vs 73%; p = 0.001). Of 12 patients (9 nNSA-ab, 2 VGKC-ab, 1 NMDAR-ab) with paraneoplastic LE and NSA-ab, concomitant intraneuronal antibodies occurred in 9 (75%). None of these 12 patients improved with immunotherapy. The autopsy of three of them showed neuronal loss, microgliosis, and cytotoxic T cell infiltrates in the hippocampus and amygdala. These findings were compatible with a T-cell mediated neuronal damage. In contrast, 13 of 17 (76%) patients with idiopathic LE and NSA-ab (8 VGKC-ab, 4 NMDAR-ab, 1 nNSA-ab) and 1 of 5 (20%) without antibodies had clinical improvement (p = 0.04). Conclusions: In paraneoplastic limbic encephalitis (LE), novel antibodies against neuronal surface antigens (nNSA-ab) occur frequently, coexist with antibodies against intracellular antigens, and these cases are refractory to immunotherapy. In idiopathic LE, the likelihood of improvement is significantly higher in patients with NSA-ab than in those without antibodies. GLOSSARY GAD = glutamic acid decarboxylase; LE = limbic encephalitis; NMDAR = N-methyl-D-aspartate receptor; NSA = neuronal surface antigens; nNSA = novel NSA; SCLC = small-cell lung cancer; VGKC = voltage-gated potassium channels