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Sample records for antibodies promising experimental

  1. Catalytic Antibodies: Concept and Promise

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 12; Issue 11. Catalytic Antibodies: Concept and Promise. Desirazu N Rao Bharath Wootla. General Article Volume 12 Issue ... Keywords. Catalytic antibodies; abzymes; hybridome technology; Diels– Alder reaction; Michaelis– Menten kinetics; Factor VIII.

  2. Biting back: BiTE antibodies as a promising therapy for acute myeloid leukemia.

    Science.gov (United States)

    Walter, Roland B

    2014-06-01

    The experience with gemtuzumab ozogamicin has highlighted both the potential value and limitations of antibodies in acute myeloid leukemia (AML). Recently, bispecific T-cell engager (BiTE) antibodies have emerged as a means to harness polyclonal cytotoxic T-cells and cause highly efficient lysis of targeted tumor cells. Promising early results have been obtained with the CD19-directed BiTE antibody, blinatumomab, in patients with acute lymphoblastic leukemia. A first candidate for AML is the CD33/CD3 molecule, AMG 330, for which several recent preclinical studies demonstrated high potency and efficacy in destroying CD33(+) human AML cells. Many questions remain to be addressed, but BiTE antibodies may offer an exciting new tool in a disease for which the outcomes in many patients remain unsatisfactory.

  3. Experimental Lung Cancer Drug Shows Early Promise | Poster

    Science.gov (United States)

    By Frank Blanchard, Staff Writer A first-of-its-kind drug is showing early promise in attacking certain lung cancers that are hard to treat because they build up resistance to conventional chemotherapy. The drug, CO-1686, performed well in a preclinical study involving xenograft and transgenic mice, as reported in the journal Cancer Discovery. It is now being evaluated for safety and efficacy in Phase I and II clinical trials.

  4. Single-Domain Antibodies and the Promise of Modular Targeting in Cancer Imaging and Treatment

    Directory of Open Access Journals (Sweden)

    María Elena Iezzi

    2018-02-01

    Full Text Available Monoclonal antibodies and their fragments have significantly changed the outcome of cancer in the clinic, effectively inhibiting tumor cell proliferation, triggering antibody-dependent immune effector cell activation and complement mediated cell death. Along with a continued expansion in number, diversity, and complexity of validated tumor targets there is an increasing focus on engineering recombinant antibody fragments for lead development. Single-domain antibodies (sdAbs, in particular those engineered from the variable heavy-chain fragment (VHH gene found in Camelidae heavy-chain antibodies (or IgG2 and IgG3, are the smallest fragments that retain the full antigen-binding capacity of the antibody with advantageous properties as drugs. For similar reasons, growing attention is being paid to the yet smaller variable heavy chain new antigen receptor (VNAR fragments found in Squalidae. sdAbs have been selected, mostly from immune VHH libraries, to inhibit or modulate enzyme activity, bind soluble factors, internalize cell membrane receptors, or block cytoplasmic targets. This succinct review is a compilation of recent data documenting the application of engineered, recombinant sdAb in the clinic as epitope recognition “modules” to build monomeric, dimeric and multimeric ligands that target, tag and stall solid tumor growth in vivo. Size, affinity, specificity, and the development profile of sdAbs drugs are seemingly consistent with desirable clinical efficacy and safety requirements. But the hepatotoxicity of the tetrameric anti-DR5-VHH drug in patients with pre-existing anti-drug antibodies halted the phase I clinical trial and called for a thorough pre-screening of the immune and poly-specific reactivities of the sdAb leads.

  5. Radioimmunoimaging of experimental gliomas using radiolabelled monoclonal antibodies

    International Nuclear Information System (INIS)

    Glaessner, H.

    1986-01-01

    The biodistribution and tumour uptake of radiolabelled (131 I) glioma-seeking monoclonal antibodies (14 AC1) and their F(ab') 2 fragments were investigated in nude mice having received glioma transplants. Radioimmunoimaging by external scintigraphy at 48 and 96 hours pointed to a superior tumour localisation by the fragments that was clearly related to the dose. Wholebody determinations of the biokinetic behaviour led to the following results: Faster clearance anc more ready elimination from the blood pool for the fragments, preferential uptake in the tumour; intact antibodies; binding in the liver, spleen and lungs. The study confirmed the value of fragments of monoclonal antibodies in the diagnosis of tumours and pointed to the possibility of using intact monoclonal antibodies as carriers of radioisotopes and cytotoxic drugs within the scope of therapeutic programmes. (TRV) [de

  6. Antibody administration in experimental influenza increases survival and enhances the effect of oseltamivir

    DEFF Research Database (Denmark)

    Pourroy, Brit Naldahl Jessen; Kolmos, Hans Jørn; Nielsen, Lars Peter

    2012-01-01

    and treatment of a number of infectious diseases. In this experimental study anti-influenza antibodies were passively administrated to mice, subsequently they were infected with influenza virus and treated with oseltamivir. The aim was to investigate, if anti-influenza antibodies influenced the out come...... be considered in the in control of influenza....

  7. Amphiregulin Antibody and Reduction of Axial Elongation in Experimental Myopia

    Directory of Open Access Journals (Sweden)

    Wen Jun Jiang

    2017-03-01

    Full Text Available To examine the mechanism of ocular axial elongation in myopia, guinea pigs (age: 2–3 weeks which either underwent unilateral or bilateral lens-induced myopization (group 1 or which were primarily myopic at baseline (group 2 received unilateral intraocular injections of amphiregulin antibody (doses: 5, 10, or 15 μg three times in intervals of 9 days. A third group of emmetropic guinea pigs got intraocular unilateral injections of amphiregulin (doses: 0.25, 0.50 or 1.00 ng, respectively. In each group, the contralateral eyes received intraocular injections of Ringer's solution. In intra-animal inter-eye comparison and intra-eye follow-up comparison in groups 1 and 2, the study eyes as compared to the contralateral eyes showed a dose-dependent reduction in axial elongation. In group 3, study eyes and control eyes did not differ significantly in axial elongation. Immunohistochemistry revealed amphiregulin labelling at the retinal pigment epithelium in eyes with lens-induced myopization and Ringer's solution injection, but not in eyes with amphiregulin antibody injection. Intraocular injections of amphiregulin-antibody led to a reduction of lens-induced axial myopic elongation and of the physiological eye enlargement in young guinea pigs. In contrast, intraocularly injected amphiregulin in a dose of ≤1 ng did not show a significant effect. Amphiregulin may be one of several essential molecular factors for axial elongation.

  8. Design of high-pressure direct contact heater for promising power supply units: Experimental substantiation

    Science.gov (United States)

    Somova, E. V.; Shvarts, A. L.; Turkin, A. V.

    2016-11-01

    The results of experimental studies of superheated steam condensation on feed water jets in a highpressure, direct-contact heat exchanger are presented. Direct contact feed water heater (DCFWH) can be used in a dual-flow diagram of a steam-power unit with ultrasupercritical steam parameters (35 MPa, 700/720°C). The direct contact feed water heater is included in the flow diagram of the II circuit in a promising power unit; it provides feed water heating to 340°C in all maintenance and emergency operation modes of the unit. The reliability of the high-pressure direct contact heater operation in this flow diagram is of major importance in relation to the danger of lead solidification in the tube space of the steam generator. Technical requirements to the design of the high-pressure direct contact heater for increasing the heat exchange efficiency are formulated based on the results of earlier studies with steam-water mixture as the heating medium. The results of studies of superheated steam condensation on jets presented in this study testify that feed water is additionally heated to the required temperature at the output of the installation. The influence of initial feed water parameters (outflow velocity and temperature) on the jet heating length is elucidated. The numerical approximation of the experimental data for determination of the jet heating length in the nominal and partial power unit loads is obtained. The results of the calculations are used to simplify the design of the water-supplying element for the direct contact feed water heater. The proposed design of direct contact feed water heater is characterized by simplicity and low metal intensity, which provides the installation reliability at the considered pressure level due to the minimum number of structural elements.

  9. Targeted proteomics reveals promising biomarkers of disease activity and organ involvement in antineutrophil cytoplasmic antibody-associated vasculitis.

    Science.gov (United States)

    Ishizaki, Jun; Takemori, Ayako; Suemori, Koichiro; Matsumoto, Takuya; Akita, Yoko; Sada, Ken-Ei; Yuzawa, Yukio; Amano, Koichi; Takasaki, Yoshinari; Harigai, Masayoshi; Arimura, Yoshihiro; Makino, Hirofumi; Yasukawa, Masaki; Takemori, Nobuaki; Hasegawa, Hitoshi

    2017-09-29

    Targeted proteomics, which involves quantitative analysis of targeted proteins using selected reaction monitoring (SRM) mass spectrometry, has emerged as a new methodology for discovery of clinical biomarkers. In this study, we used targeted serum proteomics to identify circulating biomarkers for prediction of disease activity and organ involvement in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). A large-scale SRM assay targeting 135 biomarker candidates was established using a triple-quadrupole mass spectrometer coupled with nanoflow liquid chromatography. Target proteins in serum samples from patients in the active and remission (6 months after treatment) stages were quantified using the established assays. Identified marker candidates were further validated by enzyme-linked immunosorbent assay using serum samples (n = 169) collected in a large-cohort Japanese study (the RemIT-JAV-RPGN study). Our proteomic analysis identified the following proteins as biomarkers for discriminating patients with highly active AAV from those in remission or healthy control subjects: tenascin C (TNC), C-reactive protein (CRP), tissue inhibitor of metalloproteinase 1 (TIMP1), leucine-rich alpha-2-glycoprotein 1, S100A8/A9, CD93, matrix metalloproteinase 9, and transketolase (TKT). Of these, TIMP1 was the best-performing marker of disease activity, allowing distinction between mildly active AAV and remission. Moreover, in contrast to CRP, serum levels of TIMP1 in patients with active AAV were significantly higher than those in patients with infectious diseases. The serum levels of TKT and CD93 were higher in patients with renal involvement than in those without, and they predicted kidney outcome. The level of circulating TNC was elevated significantly in patients with lung infiltration. AAV severity was associated with markers reflecting organ involvement (TKT, CD93, and TNC) rather than inflammation. The eight markers and myeloperoxidase (MPO

  10. Experimental Immunization Based on Plasmodium Antigens Isolated by Antibody Affinity

    Directory of Open Access Journals (Sweden)

    Ali N. Kamali

    2015-01-01

    Full Text Available Vaccines blocking malaria parasites in the blood-stage diminish mortality and morbidity caused by the disease. Here, we isolated antigens from total parasite proteins by antibody affinity chromatography to test an immunization against lethal malaria infection in a murine model. We used the sera of malaria self-resistant ICR mice to lethal Plasmodium yoelii yoelii 17XL for purification of their IgGs which were subsequently employed to isolate blood-stage parasite antigens that were inoculated to immunize BALB/c mice. The presence of specific antibodies in vaccinated mice serum was studied by immunoblot analysis at different days after vaccination and showed an intensive immune response to a wide range of antigens with molecular weight ranging between 22 and 250 kDa. The humoral response allowed delay of the infection after the inoculation to high lethal doses of P. yoelii yoelii 17XL resulting in a partial protection against malaria disease, although final survival was managed in a low proportion of challenged mice. This approach shows the potential to prevent malaria disease with a set of antigens isolated from blood-stage parasites.

  11. ROLE OF IL-6 IN EXPERIMENTAL ARTHRITIS CAUSED BY TRANSFER OF ARTHRITOGENIC ANTIBODIES

    Directory of Open Access Journals (Sweden)

    M. S. Drutskaya

    2016-01-01

    Full Text Available Interleukin-6 (IL-6 exerts important functions on immune regulation. In case of high expression, IL-6 may promote autoimmune disorders, e.g., arthritis. Systemic IL-6 blockers based on monoclonal antibodies against IL-6, or its specific receptor subunit, are already used in clinical settings, adding to a range of known biological drugs, such as, TNF blockers. Rheumatic disorders and their experimental therapy are reproducible in mice. This study revealed systemically increased levels of IL-6 in developing arthritis caused by transfer of pathogenic antibodies, as well as the effects of IL-6 neutralization by monoclonal antibodies against murine IL-6. Our results suggest a pathogenic role of the two cytokines, TNF and IL-6, in experimental arthritis induced by passive transfer of anti-collagen antibodies.

  12. Experimental prestorage filtration removes antibodies and decreases lipids in RBC supernatants mitigating TRALI in vivo

    Science.gov (United States)

    Kelher, Marguerite R.; Khan, Samina Y.; LaSarre, Monica; West, F. Bernadette; Land, Kevin J.; Mish, Barbara; Ceriano, Linda; Sowemimo-Coker, Samuel

    2014-01-01

    Transfusion-related acute lung injury (TRALI) remains a significant cause of transfusion-related mortality with red cell transfusion. We hypothesize that prestorage filtration may reduce proinflammatory activity in the red blood cell (RBC) supernatant and prevent TRALI. Filters were manufactured for both small volumes and RBC units. Plasma containing antibodies to human lymphocyte antigen (HLA)-A2 or human neutrophil antigen (HNA)-3a was filtered, and immunoglobulins and specific HNA-3a and HLA-2a neutrophil (PMN) priming activity were measured. Antibodies to OX27 were added to plasma, and filtration was evaluated in a 2-event animal model of TRALI. RBC units from 31 donors known to have antibodies against HLA antigens and from 16 antibody-negative controls were filtered. Furthermore, 4 RBC units were drawn and underwent standard leukoreduction. Immunoglobulins, HLA antibodies, PMN priming activity, and the ability to induce TRALI in an animal model were measured. Small-volume filtration of plasma removed >96% of IgG, antibodies to HLA-A2 and HNA-3a, and their respective priming activity, as well as mitigating antibody-mediated in vivo TRALI. In RBC units, experimental filtration removed antibodies to HLA antigens and inhibited the accumulation of lipid priming activity and lipid-mediated TRALI. We conclude that filtration removes proinflammatory activity and the ability to induce TRALI from RBCs and may represent a TRALI mitigation step. PMID:24747436

  13. Experimental radioimmunotherapy with I-131-antibody against a differentiation antigen

    International Nuclear Information System (INIS)

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

    1985-01-01

    The authors have previously shown that I-131-labeled antibodies (Ab) against the Thyl.l antigen can care AKR/Cu (Thyl.2+) mice bearing the AKR/J (Thy 1l.1+) SL2 T-cell lymphoma. The authors have now extended these studies to therapy with I-131-anti-Thyl.1 of SL2 lymphoma in AKR/J mice where Ab reacts with both tumor and normal cells. A 25 μg bolus was rapidly cleared from serum by binding to spleen cells (75% with Tl/2 <60 min.) and only low concentrations of Ab(<2% ID/gm) were present in tumor after infusion. Therapy of AKR/J mice bearing established s.c. lymphoma nodules with 1500 μCi I-131-anti-Thyl.1 resulted in complete regression of the nodule in 6/6 animals although tumor eventually regrew and all animals died of metastatic lymphoma. In contrast, I-131-irrelevant Ab given to produce the same amount of whole body radiation (750 μCi) did not affect tumor growth. These studies suggest that radiolabeled-AB against differentiation antigens may be useful for therapy in spite of binding to normal cell populations

  14. Detection of experimental myocarditis by monoclonal antimyosin antibody, Fab fragment

    Energy Technology Data Exchange (ETDEWEB)

    Rezkalla, S.; Kloner, R.A.; Khaw, B.A.; Haber, E.; Fallon, J.T.; Smith, F.E.; Khatib, R.

    1989-02-01

    The purpose of this study was to determine whether monoclonal antimyosin Fab (antigen binding fragment) was capable of labeling hearts with experimental coxsackievirus myocarditis, and to determine whether Fab could be used for detecting myocardial damage in either early or chronic phases of the disease. Sixty-five, 3-week-old cesarean-derived 1 (CD 1) mice were divided into two groups: group I (noninfected animals) and group II (infected with coxsackievirus B3). Mice from each group were killed on days 7, 17, 30, or 90 of infection. Forty-eight hours before killing, mice were injected with monoclonal I-125 antimyosin, Fab (25 microCi/injection) and radioactivity was counted in the heart. Selected heart sections were also examined by autoradiography. Heart radioactivity, count/m/mg (m +/- SEM) on days 7, 17, 30, and 90 of infection was 10.8 +/- 1.7, 21.3 +/- 1.1, 11.2 +/- 3.4, and 12.4 +/- 1.5 for group I, versus 36.7 +/- 8.0 (p less than 0.01), 50.0 +/- 4.5 (p less than 0.001), 33.4 +/- 16.1 (p = NS), and 40.6 +/- 8.5 (p less than 0.01) for group II, respectively. Autoradiography revealed focal uptake within areas of necrotic myocardium. We conclude that I125 Fab may be useful in detecting myocardial damage in the experimental model of murine myocarditis up to day 90 of infection.

  15. Detection of experimental myocarditis by monoclonal antimyosin antibody, Fab fragment

    International Nuclear Information System (INIS)

    Rezkalla, S.; Kloner, R.A.; Khaw, B.A.; Haber, E.; Fallon, J.T.; Smith, F.E.; Khatib, R.

    1989-01-01

    The purpose of this study was to determine whether monoclonal antimyosin Fab (antigen binding fragment) was capable of labeling hearts with experimental coxsackievirus myocarditis, and to determine whether Fab could be used for detecting myocardial damage in either early or chronic phases of the disease. Sixty-five, 3-week-old cesarean-derived 1 (CD 1) mice were divided into two groups: group I (noninfected animals) and group II (infected with coxsackievirus B3). Mice from each group were killed on days 7, 17, 30, or 90 of infection. Forty-eight hours before killing, mice were injected with monoclonal I-125 antimyosin, Fab (25 microCi/injection) and radioactivity was counted in the heart. Selected heart sections were also examined by autoradiography. Heart radioactivity, count/m/mg (m +/- SEM) on days 7, 17, 30, and 90 of infection was 10.8 +/- 1.7, 21.3 +/- 1.1, 11.2 +/- 3.4, and 12.4 +/- 1.5 for group I, versus 36.7 +/- 8.0 (p less than 0.01), 50.0 +/- 4.5 (p less than 0.001), 33.4 +/- 16.1 (p = NS), and 40.6 +/- 8.5 (p less than 0.01) for group II, respectively. Autoradiography revealed focal uptake within areas of necrotic myocardium. We conclude that I125 Fab may be useful in detecting myocardial damage in the experimental model of murine myocarditis up to day 90 of infection

  16. A radioimmunoassay method for the rapid detection of Candida antibodies is experimental systematic candidiasis

    International Nuclear Information System (INIS)

    Huang, Y.; Berry, W.; Cooper, H.; Zachariah, Y.; Newman, T.

    1979-01-01

    Rabbits were employed as experimental models to evaluate a solid-phase radioimmunoassay (RIA) method for the diagnosis of systematic candidiasis. Ten rabbits were incubated subcutaneously to mimic superficial candidiasis and were found to produce no antibodies to Candida as determined by both immunodiffusion and RIA procedures. However, 94 per cent of 18 rabbits systematically infected by intravenous injection of Candida cells were observed to produce antibody as assessed by the RIA technique. These data encourage further tests with human sera and the continued development of this RIA procedure as a useful tool in the early serodiagnosis of systematic candidiasis. (Auth.)

  17. Shaping beliefs in experimental markets for expert services: Guilt aversion and the impact of promises and money-burning options.

    Science.gov (United States)

    Beck, Adrian; Kerschbamer, Rudolf; Qiu, Jianying; Sutter, Matthias

    2013-09-01

    In a credence goods game with an expert and a consumer, we study experimentally the impact of two devices that are predicted to induce consumer-friendly behavior if the expert has a propensity to feel guilty when he believes that he violates the consumer's payoff expectations: (i) an opportunity for the expert to make a non-binding promise; and (ii) an opportunity for the consumer to burn money. In belief-based guilt aversion theory the first opportunity shapes an expert's behavior if an appropriate promise is made and if it is expected to be believed by the consumer; by contrast, the second opportunity might change behavior even though this option is never used along the predicted path. Experimental results confirm the behavioral relevance of (i) but fail to confirm (ii).

  18. Detection of antibodies to single-stranded DNA in naturally acquired and experimentally induced viral hepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Gust, I.D.; Feinstone, S.M.; Purcell, R.H.; Alter, H.J.

    1980-01-01

    A sensitive ''Farr'' assay, utilizing /sup 125/I-labelled DNA was developed for detecting antibody to single-stranded DNA (anti-ssDNA). The test was shown to be specific and as sensitive as assays using /sup 14/C-labelled DNA, for the detection of antibody in patients with connective tissue diseases. Groups of sera from patients with naturally acquired viral hepatitis and experimentally infected chimpanzees were tested for anti-ssDNA by the /sup 125/I assay and by counterimmunoelectrophoresis (CIEP). No consistent pattern was observed with either technique, indicating the elevated levels of this antibody are not as reliable markers of parenchymal liver damage as had been previously suggested.

  19. Experimental studies of low salinity water flooding in carbonate reservoirs: A new promising approach

    DEFF Research Database (Denmark)

    Zahid, Adeel; Shapiro, Alexander; Skauge, Arne

    2012-01-01

    Low salinity water flooding is well studied for sandstone reservoirs, both laboratory and field tests have showed improvement in the oil recovery in many cases. Up to very recently, the low salinity effect has been indeterminated for carbonates. Most recently, Saudi Aramco reported that substantial...... reservoirs. In this paper, we have experimentally investigated the oil recovery potential of low salinity water flooding for carbonate rocks. We used both reservoir carbonate and outcrop chalk core plugs. The flooding experiments were carried out initially with the seawater, and afterwards additional oil...... both at ambient and high temperature. No low salinity effect was observed for the reservoir carbonate core plug at the ambient temperature, but increase of the pressure drop over the core plug was detected. On the contrary, a significant increase in oil recovery was observed under low salinity flooding...

  20. LHC experimental data from today's data challenges to the promise of tomorrow

    CERN Multimedia

    CERN. Geneva; Panzer-Steindel, Bernd; Rademakers, Fons

    2003-01-01

    The LHC experiments constitute a challenge in several discipline in both High Energy Physics and Information Technologies. This is definitely the case for data acquisition, processing and analysis. This challenge has been addressed by many years or R&D activity during which prototypes of components or subsystems have been developed. This prototyping phase is now culminating with an evaluation of the prototypes in large-scale tests (approximately called "Data Challenges"). In a period of restricted funding, the expectation is to realize the LHC data acquisition and computing infrastructures by making extensive use of standard and commodity components. The lectures will start with a brief overview of the requirements of the LHC experiments in terms of data acquisition and computing. The different tasks of the experimental data chain will also be explained: data acquisition, selection, storage, processing and analysis. The major trends of the computing and networking industries will then be indicated with pa...

  1. Experimental studies of low salinity water flooding in carbonate reservoirs: A new promising approach

    DEFF Research Database (Denmark)

    Zahid, Adeel; Shapiro, Alexander; Skauge, Arne

    2012-01-01

    reservoirs. In this paper, we have experimentally investigated the oil recovery potential of low salinity water flooding for carbonate rocks. We used both reservoir carbonate and outcrop chalk core plugs. The flooding experiments were carried out initially with the seawater, and afterwards additional oil......Low salinity water flooding is well studied for sandstone reservoirs, both laboratory and field tests have showed improvement in the oil recovery in many cases. Up to very recently, the low salinity effect has been indeterminated for carbonates. Most recently, Saudi Aramco reported that substantial...... recovery was evaluated by sequential injection of various diluted seawater. The experiments applied stepwise increase in flow rate to eliminate the influence of possible capillary end effect. The total oil recovery, interaction of the different ions with the rock, and the wettability changes were studied...

  2. Phase Behavior Modeling of Asphaltene Precipitation for Heavy Crudes: A Promising Tool Along with Experimental Data

    Science.gov (United States)

    Tavakkoli, M.; Kharrat, R.; Masihi, M.; Ghazanfari, M. H.; Fadaei, S.

    2012-12-01

    Thermodynamic modeling is known as a promising tool for phase behavior modeling of asphaltene precipitation under different conditions such as pressure depletion and CO2 injection. In this work, a thermodynamic approach is used for modeling the phase behavior of asphaltene precipitation. The precipitated asphaltene phase is represented by an improved solid model, while the oil and gas phases are modeled with an equation of state. The PR-EOS was used to perform flash calculations. Then, the onset point and the amount of precipitated asphaltene were predicted. A computer code based on an improved solid model has been developed and used for predicting asphaltene precipitation data for one of Iranian heavy crudes, under pressure depletion and CO2 injection conditions. A significant improvement has been observed in predicting the asphaltene precipitation data under gas injection conditions. Especially for the maximum value of asphaltene precipitation and for the trend of the curve after the peak point, good agreement was observed. For gas injection conditions, comparison of the thermodynamic micellization model and the improved solid model showed that the thermodynamic micellization model cannot predict the maximum of precipitation as well as the improved solid model. The non-isothermal improved solid model has been used for predicting asphaltene precipitation data under pressure depletion conditions. The pressure depletion tests were done at different levels of temperature and pressure, and the parameters of a non-isothermal model were tuned using three onset pressures at three different temperatures for the considered crude. The results showed that the model is highly sensitive to the amount of solid molar volume along with the interaction coefficient parameter between the asphaltene component and light hydrocarbon components. Using a non-isothermal improved solid model, the asphaltene phase envelope was developed. It has been revealed that at high temperatures, an

  3. Gag- and env-specific serum antibodies in cats after natural and experimental infection with feline immunodeficiency virus.

    NARCIS (Netherlands)

    G.F. Rimmelzwaan (Guus); C.H.J. Siebelink (Kees); H. Broos; G.A. Drost; K. Weijer (Kees); R. van Herwijnen (Rob); A.D.M.E. Osterhaus (Albert)

    1994-01-01

    textabstractIn order to monitor the antibody response to feline immunodeficiency virus (FIV) in cats, following experimental and natural infection, enzyme-linked immunosorbent assays (ELISAs) were developed using recombinant env and gag proteins and p24-specific monoclonal antibodies. It was shown

  4. Adjuvant treatment with dexamethasone plus anti-C5 antibodies improves outcome of experimental pneumococcal meningitis: a randomized controlled trial

    NARCIS (Netherlands)

    Kasanmoentalib, E. Soemirien; Valls Seron, Mercedes; Morgan, B. Paul; Brouwer, Matthijs C.; van de Beek, Diederik

    2015-01-01

    We compared adjunctive treatment with placebo, dexamethasone, anti-C5 antibodies, and the combination of dexamethasone plus anti-C5 antibodies in experimental pneumococcal meningitis. In this prospective, investigator-blinded, randomized trial, 96 mice were infected intracisternally with 10(7)

  5. Antibody responses of cervids (Cervus elaphus) following experimental Mycobacterium bovis infection and the implications for immunodiagnosis.

    Science.gov (United States)

    Harrington, Noel P; Surujballi, Om P; Prescott, John F; Duncan, J Robert; Waters, W Ray; Lyashchenko, Konstantin; Greenwald, Rena

    2008-11-01

    Captive and free-ranging wildlife animals are implicated in the maintenance and transmission of bovine tuberculosis and therefore pose a significant obstacle to eradication of the disease from domestic livestock. The current antemortem diagnostic method, the intradermal tuberculin skin test, is impractical for routine use with many wild animals. Antibody-based assays are particularly attractive because the animals are handled only once and immediate processing of the sample is not required. This report characterizes the antibody responses of red deer-elk hybrids (Cervus elaphus) against Mycobacterium bovis and subsequently evaluates the diagnostic performance of select antigens in a rapid-test format. Sequential serum samples were collected from 10 animals experimentally infected with M. bovis and 5 noninfected animals over a 7-month period postinfection (p.i.). Samples were evaluated by enzyme-linked immunosorbent assays, immunoblot analyses, and multiantigen print immunoassays for seroreactivity to mycobacterial antigens. Although all infected animals produced antibodies to M. bovis protein antigens, there was significant animal-to-animal variation in the kinetics and magnitudes of responses and the antigens recognized. The most frequently recognized antigens included MPB83, ESAT-6, CFP10, and MPB70. Responses to some antigens, such as MPB83, were consistently detected as early as 4 weeks after inoculation, whereas other antigens were detected only much later (>140 days p.i.). Antibody responses were boosted by injection of tuberculin for intradermal tuberculin skin testing. Comparison of single-antigen (fluorescence polarization assay) with multiantigen (CervidTB STAT-PAK) rapid tests demonstrated that a highly sensitive and specific serodiagnostic test for tuberculosis in cervids will require multiple and carefully selected seroreactive antigens covering a broad spectrum of antibody specificities.

  6. Adjuvant treatment with dexamethasone plus anti-C5 antibodies improves outcome of experimental pneumococcal meningitis: a randomized controlled trial.

    Science.gov (United States)

    Kasanmoentalib, E Soemirien; Valls Seron, Mercedes; Morgan, B Paul; Brouwer, Matthijs C; van de Beek, Diederik

    2015-08-15

    We compared adjunctive treatment with placebo, dexamethasone, anti-C5 antibodies, and the combination of dexamethasone plus anti-C5 antibodies in experimental pneumococcal meningitis. In this prospective, investigator-blinded, randomized trial, 96 mice were infected intracisternally with 10(7) CFU/ml Streptococcus pneumoniae serotype 3, treated with intraperitoneal ceftriaxone at 20 h, and randomly assigned to intraperitoneal adjunctive treatment with placebo (saline), dexamethasone, anti-C5 antibodies, or dexamethasone plus anti-C5 antibodies. The primary outcome was survival during a 72-h observational period that was analyzed with the log-rank test. Secondary outcome was clinical severity, scored on a validated scale using a linear mixed model. Mortality rates were 16 of 16 mice (100%) in the placebo group, 12 of 15 mice (80%) in the dexamethasone group, 25 of 31 mice (80%) in the anti-C5 antibody group, and 18 of 30 mice (60%) in the dexamethasone plus anti-C5 antibody group (Fisher's exact test for overall difference, P = .012). Mortality of mice treated with dexamethasone plus anti-C5 antibodies was lower compared to the anti-C5 antibody-treated mice (log-rank P = .039) and dexamethasone-treated mice (log-rank P = .040). Clinical severity scores for the dexamethasone plus anti-C5 antibody-treated mice increased more slowly (0.199 points/h) as compared to the anti-C5 antibody-treated mice (0.243 points/h, P = .009) and dexamethasone-treated mice (0.249 points/h, P = .012). Modeling of severity data suggested an additive effect of dexamethasone and anti-C5 antibodies. Adjunctive treatment with dexamethasone plus anti-C5 antibodies improves survival in severe experimental meningitis caused by S. pneumoniae serotype 3, posing an important new treatment strategy for patients with pneumococcal meningitis.

  7. Preliminary study of experimental tumor radioimmunoimagination in animals by CA-50 monoclonal antibody

    International Nuclear Information System (INIS)

    Chen zhizhou

    1988-01-01

    The 125 I labelling of CA-50 monoclonal antibody, the distribution of radioactivity in experimental lung cancer 739 bearing mice, and tumor radioimmunoimagination were studied. At 24 hrs after the i.v. administrations of 5.55∼8.14 MBq 125 I-CA50, the relative values of radioactivity in different tissues were: muscle 1, blood 4.1, heart 1.4, liver 6.7, spleen 2.2, lung 2.8, kidney 5.3, tumor 14.5. Radioimmunoimagination showed clearly the locatization of the tumor

  8. BAFF mediates splenic B cell response and antibody production in experimental Chagas disease.

    Directory of Open Access Journals (Sweden)

    Daniela A Bermejo

    Full Text Available BACKGROUND: B cells and antibodies are involved not only in controlling the spread of blood circulating Trypanosoma cruzi, but also in the autoreactive manifestations observed in Chagas disease. Acute infection results in polyclonal B cell activation associated with hypergammaglobulinemia, delayed specific humoral immunity and high levels of non-parasite specific antibodies. Since TNF superfamily B lymphocyte Stimulator (BAFF mediates polyclonal B cell response in vitro triggered by T. cruzi antigens, and BAFF-Tg mice show similar signs to T. cruzi infected mice, we hypothesized that BAFF can mediate polyclonal B cell response in experimental Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: BAFF is produced early and persists throughout the infection. To analyze BAFF role in experimental Chagas disease, Balb/c infected mice were injected with BR3:Fc, a soluble receptor of BAFF, to block BAFF activity. By BAFF blockade we observed that this cytokine mediates the mature B cell response and the production of non-parasite specific IgM and IgG. BAFF also influences the development of antinuclear IgG and parasite-specific IgM response, not affecting T. cruzi-specific IgG and parasitemia. Interestingly, BAFF inhibition favors the parasitism in heart. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate, for the first time, an active role for BAFF in shaping the mature B cell repertoire in a parasite infection.

  9. Experimental Protocol for Detecting Cyanobacteria in Liquid and Solid Samples with an Antibody Microarray Chip.

    Science.gov (United States)

    Blanco, Yolanda; Moreno-Paz, Mercedes; Parro, Victor

    2017-02-07

    Global warming and eutrophication make some aquatic ecosystems behave as true bioreactors that trigger rapid and massive cyanobacterial growth; this has relevant health and economic consequences. Many cyanobacterial strains are toxin producers, and only a few cells are necessary to induce irreparable damage to the environment. Therefore, water-body authorities and administrations require rapid and efficient early-warning systems providing reliable data to support their preventive or curative decisions. This manuscript reports an experimental protocol for the in-field detection of toxin-producing cyanobacterial strains by using an antibody microarray chip with 17 antibodies (Abs) with taxonomic resolution (CYANOCHIP). Here, a multiplex fluorescent sandwich microarray immunoassay (FSMI) for the simultaneous monitoring of 17 cyanobacterial strains frequently found blooming in freshwater ecosystems, some of them toxin producers, is described. A microarray with multiple identical replicates (up to 24) of the CYANOCHIP was printed onto a single microscope slide to simultaneously test a similar number of samples. Liquid samples can be tested either by direct incubation with the antibodies (Abs) or after cell concentration by filtration through a 1- to 3-μm filter. Solid samples, such as sediments and ground rocks, are first homogenized and dispersed by a hand-held ultrasonicator in an incubation buffer. They are then filtered (5 - 20 μm) to remove the coarse material, and the filtrate is incubated with Abs. Immunoreactions are revealed by a final incubation with a mixture of the 17 fluorescence-labeled Abs and are read by a portable fluorescence detector. The whole process takes around 3 h, most of it corresponding to two 1-h periods of incubation. The output is an image, where bright spots correspond to the positive detection of cyanobacterial markers.

  10. Imaging endocarditis with Tc-99m-labeled antibody--an experimental study: concise communication

    Energy Technology Data Exchange (ETDEWEB)

    Wong, D.W.; Dhawan, V.K.; Tanaka, T.; Mishkin, F.S.; Reese, I.C.; Thadepalli, H.

    1982-03-01

    The sensitivity and specificity of Tc-99m-labeled antibacterial antibody (Tc-99m Ab) for detecting bacterial endocarditis were evaluated in an experimental model. Rabbit-produced antistaphylococcal antibody was extracted using Rivanol and chemically labeled with Tc-99m. This Tc-99m Ab was injected intravenously in New Zealand rabbits 24 hr after producing Staphylococcus aureus endocarditis of the aortic valve. Imaging and tissue analyses were performed on the following day. All 11 animals developed S. aureus aortic-valve vegetations and showed increased uptake of Tc-99m Ab at the aortic valve, 118 times higher than at the uninfected tricuspid valve. Although high hepatic radioactivity and anatomic uncertainties interfered with in vivo delineation of these lesions, images of the excised hearts showed all affected valves. Two rabbits inoculated with Escherichia coli did not develop endocarditis and had little uptake of Tc-99m Ab, while six rabbits with enterococcal endocarditis had no uptake of the Tc-99m Ab in their vegetations. The findings suggest potential value of Tc-99m Ab on the rapid diagnosis of endocarditis.

  11. Imaging endocarditis with Tc-99m-labeled antibody--an experimental study: concise communication

    International Nuclear Information System (INIS)

    Wong, D.W.; Dhawan, V.K.; Tanaka, T.; Mishkin, F.S.; Reese, I.C.; Thadepalli, H.

    1982-01-01

    The sensitivity and specificity of Tc-99m-labeled antibacterial antibody (Tc-99m Ab) for detecting bacterial endocarditis were evaluated in an experimental model. Rabbit-produced antistaphylococcal antibody was extracted using Rivanol and chemically labeled with Tc-99m. This Tc-99m Ab was injected intravenously in New Zealand rabbits 24 hr after producing Staphylococcus aureus endocarditis of the aortic valve. Imaging and tissue analyses were performed on the following day. All 11 animals developed S. aureus aortic-valve vegetations and showed increased uptake of Tc-99m Ab at the aortic valve, 118 times higher than at the uninfected tricuspid valve. Although high hepatic radioactivity and anatomic uncertainties interfered with in vivo delineation of these lesions, images of the excised hearts showed all affected valves. Two rabbits inoculated with Escherichia coli did not develop endocarditis and had little uptake of Tc-99m Ab, while six rabbits with enterococcal endocarditis had no uptake of the Tc-99m Ab in their vegetations. The findings suggest potential value of Tc-99m Ab on the rapid diagnosis of endocarditis

  12. Detection of antibodies against Theiler's murine encephalomyelitis virus GDVII strain in experimental guinea pigs.

    Science.gov (United States)

    Häger, C; Glage, S; Held, N; Bleich, E M; Burghard, A; Mähler, M; Bleich, André

    2016-10-01

    A disease affecting guinea pigs called 'guinea pig lameness' characterized by clinical signs of depression, lameness of limbs, flaccid paralysis, weight loss and death within a few weeks was first described by Römer in 1911. After a research group in our facility kept laboratory guinea pigs from two different origins together in one room, lameness was observed in two animals. Further investigations revealed a serological immune response against Theiler's murine encephalomyelitis virus (TMEV; GDVII strain) in these animals. Histopathology of the lumbar spinal cord of these animals showed mononuclear cell infiltration and necrotic neurons in the anterior horn. Therefore, all guinea pigs from this contaminated animal unit, from other units in our facility, as well as from different European institutions and breeding centres were screened for antibodies directed against GDVII. Our investigations showed that approximately 80% of all guinea pigs from the contaminated animal unit were seropositive for GDVII, whereas animals from other separate units were completely negative. In addition, 43% of tested sera from the different European institutions and breeding centres contained antibodies against GDVII. The present data confirm that an unknown viral infection causes an immune response in experimental guinea pigs leading to seroconversion against GDVII and that guinea pigs from a commercial breeder are the source of the infection. © The Author(s) 2015.

  13. Antibody binding constants from Farr test and other radioimmunoassays. A theoretical and experimental analysis

    International Nuclear Information System (INIS)

    Engel, J.; Schalch, W.

    1980-01-01

    For the reaction of monovalently reacting antibody (116-700pIEF) with its antigen (streptococcal group A-variant polysaccharide), an apparent binding constant Ksub(a) was derived by the ammonium sulfate precipitation technique (Farr assay) which was 40 times larger than the true binding constant K = 10 6 M -1 determined by fluorescence titration and equilibrium dialysis. For monovalently reacting antibodies the time needed for re-equilibration of the binding reaction is short as compared to the time of ammonium sulfate incubation. A thermodynamic analysis was therefore performed for the case of complete equilibration of all components in solution and in the ammonium sulfate precipitate. It was found that in this limiting case Ksub(a)/K is equal to the ratio of the solubilities of the antibody and the antibody complex corrected by the activity coefficients of the components in the precipitate. For other antibody-antigen reactions in which the antibody reacts with both binding sites to the same antigen molecule, re-equilibration of the binding reaction in solution is much slower. For such systems a disturbance of the binding reaction by the precipitation is less likely and correct binding constants may be obtained by the Farr technique or other radioimmunoassays involving precipitation. (author)

  14. Special issue on experimentation for climate change solutions editorial : The search for climate change and sustainability solutions - The promise and the pitfalls of experimentation

    NARCIS (Netherlands)

    Hildén, Mikael; Jordan, Andrew; Huitema, Dave

    2017-01-01

    This editorial highlights the diversity in studies of experimentation that aims for solutions to climate change and wider sustainability challenges. The diversity is reflected in the theoretical underpinnings, the agency behind experiments, the niches in which experimentation occurs, in the

  15. An experimental design approach to optimize an amperometric immunoassay on a screen printed electrode for Clostridium tetani antibody determination.

    Science.gov (United States)

    Patris, Stéphanie; Vandeput, Marie; Kenfack, Gersonie Momo; Mertens, Dominique; Dejaegher, Bieke; Kauffmann, Jean-Michel

    2016-03-15

    An immunoassay for the determination of anti-tetani antibodies has been developed using a screen printed electrode (SPE) as solid support for toxoid (antigen) immobilization. The assay was performed in guinea pig serum. The immunoreaction and the subsequent amperometric detection occurred directly onto the SPE surface. The assay consisted of spiking the anti-tetani sample directly onto the toxoid modified SPE, and then a second antibody, i.e. a HRP-labeled anti-immunoglobulin G, was deposited onto the biosensor. Subsequent amperometric detection was realized by spiking 10 µL of a hydroquinone (HQ) solution into 40 µL of buffer solution containing hydrogen peroxide. An experimental design approach was implemented for the optimization of the immunoassay. The variables of interest, such as bovine serum albumin (BSA) concentration, incubation times and labeled antibody dilution, were optimized with the aid of the response surface methodology using a circumscribed central composite design (CCCD). It was observed that two factors exhibited the greatest impact on the response, i.e. the anti-tetani incubation time and the dilution factor of the labeled antibody. It was discovered that in order to maximize the response, the dilution factor should be small, while the anti-tetani antibody incubation time should be long. The BSA concentration and the HRP-anti-IgG incubation had very limited influence. Under the optimized conditions, the immunoassay had a limit of detection of 0.011 IU/mL and a limit of quantification of 0.012 IU/mL. These values were below the protective human antibody limit of 0.06 IU/mL. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Use of Tc-rCRP as a target for lytic antibody titration after experimental Trypanosoma cruzi infection.

    Science.gov (United States)

    Marques, Tatiane; Silva, Gustavo Caetano; Henrique Paiva, Priscila Moraes; Nascentes, Gabriel Antônio Nogueira; Ramirez, Luis Eduardo; Norris, Karen; Meira, Wendell Sérgio Ferreira

    2018-01-01

    Experimental Chagas disease has been used as a model to identify several host/parasite interaction factors involved in immune responses to Trypanosoma cruzi infection. One of the factors inherent to this parasite is the complement regulatory protein (Tc-CRP), a major epitope that induces production of lytic antibodies during T. cruzi infections. Previous studies have evaluated the function of Tc-CRP as an antigenic marker via ELISAs, which demonstrated high sensitivity and specificity when compared to other methods. Therefore, this study aimed to assess and compare the levels of lytic antibodies induced by this protein following experimental infection using different T. cruzi strains. Our results demonstrated that infections induced by strains isolated from vectors resulted in subpatent parasitaemia and low reactivity, as assessed by Tc-rCRP ELISAs. On the other hand, mice inoculated with T. cruzi strains isolated from patients developed patent parasitaemia, and presented elevated lytic antibodies titres, as measured by Tc-rCRP ELISA. In addition, comparison between different mouse lineages demonstrated that Balb/c mice were more reactive than C57BL/6 mice in almost all types of infections, except those infected by the AQ-4 strain. Parasites from the Hel strain generated the greatest lytic antibody response in all evaluated models. Therefore, application of sensitive techniques for monitoring immune responses would enable us to establish growth curves for lytic antibodies during the course of the infection, and allow us to discriminate between T. cruzi strains that originate from different hosts. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Shaping beliefs in experimental markets for expert services: Guilt aversion and the impact of promises and money-burning options☆☆☆

    Science.gov (United States)

    Beck, Adrian; Kerschbamer, Rudolf; Qiu, Jianying; Sutter, Matthias

    2013-01-01

    In a credence goods game with an expert and a consumer, we study experimentally the impact of two devices that are predicted to induce consumer-friendly behavior if the expert has a propensity to feel guilty when he believes that he violates the consumerʼs payoff expectations: (i) an opportunity for the expert to make a non-binding promise; and (ii) an opportunity for the consumer to burn money. In belief-based guilt aversion theory the first opportunity shapes an expertʼs behavior if an appropriate promise is made and if it is expected to be believed by the consumer; by contrast, the second opportunity might change behavior even though this option is never used along the predicted path. Experimental results confirm the behavioral relevance of (i) but fail to confirm (ii). PMID:24003266

  18. Fuzzy promises

    DEFF Research Database (Denmark)

    Anker, Thomas Boysen; Kappel, Klemens; Eadie, Douglas

    2012-01-01

    This article clarifies the commonplace assumption that brands make promises by developing definitions of brand promise delivery. Distinguishing between clear and fuzzy brand promises, we develop definitions of what it is for a brand to deliver on fuzzy functional, symbolic, and experiential...

  19. Shaping beliefs in experimental markets for expert services: Guilt aversion and the impact of promises and money-burning options

    NARCIS (Netherlands)

    Beck, A.; Kerschbamer, R.; Qiu, J.; Sutter, M.

    2013-01-01

    In a credence goods game with an expert and a consumer, we study experimentally the impact of two devices that are predicted to induce consumer-friendly behavior if the expert has a propensity to feel guilty when he believes that he violates the consumer's payoff expectations: (i) an opportunity for

  20. Experimental results of antigliadin antibodies detection using long period fiber grating

    Science.gov (United States)

    Corres, J. M.; Matias, I. R.; Goicoechea, J.; Arregui, F. J.; Viegas, D.; Araújo, F. M.; Santos, J. L.

    2008-04-01

    In this work a new nano-biofilm is proposed for the detection of celiac disease (CD). A long-period fiber grating (LPFG) is used as a transducer and the surface of the fiber is coated with a precursor layer of SiO2-nanospheres using the electrostatic self-assembly technique (ESA). This layer has been designed in order to create a substrate of high porosity where the gliadins could be deposited. Under the presence of specific antibodies antigliadin antibodies (AGA) the refractive index of the overlay changes giving a detectable shift in the resonance wavelength of the LPFG. Concentrations as low as 5 ppm were detected.

  1. Experimental neosporosis in bulls: parasite detection in semen and blood and specific antibody and interferon-gamma responses.

    Science.gov (United States)

    Serrano-Martínez, E; Ferre, I; Martínez, A; Osoro, K; Mateos-Sanz, A; Del-Pozo, I; Aduriz, G; Tamargo, C; Hidalgo, C O; Ortega-Mora, L M

    2007-04-01

    To investigate the presence of Neospora caninum in semen and blood, and the development of specific antibody and interferon-gamma (IFN-gamma) responses in experimentally infected bulls. Eight bulls were intravenously infected with 10(8) live N. caninum tachyzoites of NC-1 isolate. The presence of N. caninum in semen and blood was assessed using a nested-PCR procedure. PCR-positive semen samples were bioassayed using a BALB/c nu/nu mouse model. Specific anti-N. caninum antibody and IFN-gamma responses were also examined. In parallel, eight seronegative bulls were studied as non-infected controls. All bulls were monitored for 26 weeks. All eight experimentally infected bulls showed N. caninum DNA in their semen and/or blood samples at some time during the course of the study. Parasite load in semen ranged from 0.1 to 14.5 parasites/ml (mean 6.0). N. caninum could not be detected in BALB/c nu/nu mice inoculated with PCR-positive semen samples. A significant increase in mean serum specific IgM antibody response to N. caninum was detected between 10 and 28 days post-infection (p.i.). Serum specific IgG, IgG1, and IgG2 antibody levels in experimentally infected bulls were significantly different after 21, 10, and 14 days p.i. as compared to controls, respectively. Specific anti-N. caninum IgG were detected in seminal plasma from infected bulls and values obtained were different from controls after 25 days p.i. Mean specific IFN-gamma responses in experimentally infected bulls were significantly higher than controls 3 days p.i. This is the first study to report the presence of N. caninum DNA in the semen and blood of experimentally infected bulls. Our observations indicate an intermittent presence of N. caninum in low numbers in semen and associated with chronic stage of the infection. This study is also the first to report the detection of anti-N. caninum IgG in seminal plasma of experimentally infected bulls.

  2. Antibody Responses of Cervids (Cervus elaphus) following Experimental Mycobacterium bovis Infection and the Implications for Immunodiagnosis ▿

    Science.gov (United States)

    Harrington, Noel P.; Surujballi, Om P.; Prescott, John F.; Duncan, J. Robert; Waters, W. Ray; Lyashchenko, Konstantin; Greenwald, Rena

    2008-01-01

    Captive and free-ranging wildlife animals are implicated in the maintenance and transmission of bovine tuberculosis and therefore pose a significant obstacle to eradication of the disease from domestic livestock. The current antemortem diagnostic method, the intradermal tuberculin skin test, is impractical for routine use with many wild animals. Antibody-based assays are particularly attractive because the animals are handled only once and immediate processing of the sample is not required. This report characterizes the antibody responses of red deer-elk hybrids (Cervus elaphus) against Mycobacterium bovis and subsequently evaluates the diagnostic performance of select antigens in a rapid-test format. Sequential serum samples were collected from 10 animals experimentally infected with M. bovis and 5 noninfected animals over a 7-month period postinfection (p.i.). Samples were evaluated by enzyme-linked immunosorbent assays, immunoblot analyses, and multiantigen print immunoassays for seroreactivity to mycobacterial antigens. Although all infected animals produced antibodies to M. bovis protein antigens, there was significant animal-to-animal variation in the kinetics and magnitudes of responses and the antigens recognized. The most frequently recognized antigens included MPB83, ESAT-6, CFP10, and MPB70. Responses to some antigens, such as MPB83, were consistently detected as early as 4 weeks after inoculation, whereas other antigens were detected only much later (>140 days p.i.). Antibody responses were boosted by injection of tuberculin for intradermal tuberculin skin testing. Comparison of single-antigen (fluorescence polarization assay) with multiantigen (CervidTB STAT-PAK) rapid tests demonstrated that a highly sensitive and specific serodiagnostic test for tuberculosis in cervids will require multiple and carefully selected seroreactive antigens covering a broad spectrum of antibody specificities. PMID:18815233

  3. Antibody and T-cell responses associated with experimental human malaria infection or vaccination show limited relationships.

    Science.gov (United States)

    Walker, Karen M; Okitsu, Shinji; Porter, David W; Duncan, Christopher; Amacker, Mario; Pluschke, Gerd; Cavanagh, David R; Hill, Adrian V S; Todryk, Stephen M

    2015-05-01

    This study examined specific antibody and T-cell responses associated with experimental malaria infection or malaria vaccination, in malaria-naive human volunteers within phase I/IIa vaccine trials, with a view to investigating inter-relationships between these types of response. Malaria infection was via five bites of Plasmodium falciparum-infected mosquitoes, with individuals reaching patent infection by 11-12 days, having harboured four or five blood-stage cycles before drug clearance. Infection elicited a robust antibody response against merozoite surface protein-119 , correlating with parasite load. Classical class switching was seen from an early IgM to an IgG1-dominant response of increasing affinity. Malaria-specific T-cell responses were detected in the form of interferon-γ and interleukin-4 (IL-4) ELIspot, but their magnitude did not correlate with the magnitude of antibody or its avidity, or with parasite load. Different individuals who were immunized with a virosome vaccine comprising influenza antigens combined with P. falciparum antigens, demonstrated pre-existing interferon-γ, IL-2 and IL-5 ELIspot responses against the influenza antigens, and showed boosting of anti-influenza T-cell responses only for IL-5. The large IgG1-dominated anti-parasite responses showed limited correlation with T-cell responses for magnitude or avidity, both parameters being only negatively correlated for IL-5 secretion versus anti-apical membrane antigen-1 antibody titres. Overall, these findings suggest that cognate T-cell responses across a range of magnitudes contribute towards driving potentially effective antibody responses in infection-induced and vaccine-induced immunity against malaria, and their existence during immunization is beneficial, but magnitudes are mostly not inter-related. © 2014 John Wiley & Sons Ltd.

  4. Serum antibody responses in Creole kids experimentally infected with Haemonchus contortus

    NARCIS (Netherlands)

    Bambou, Jean-Christophe; de la Chevrotière, Claudia; Varo, Hugues; Arquet, Remy; Kooyman, Frans N J; Mandonnet, Nathalie

    2008-01-01

    The objective of this study was to evaluate the relationship of parasite-specific serum antibodies with the resistance status of Creole kids. The average breeding values on egg output predicted in a context of natural infection at 11 months of age were distant of 1.07 genetic standard deviation

  5. An Experimental Study on Production of Egg Yolk Antibody(IgY against Bee Venom

    Directory of Open Access Journals (Sweden)

    Hwang, Tae-Jun

    2001-06-01

    Full Text Available This study was carried out for production of neutral antibody to bee venom(anti-phospholipase A2 IgY. Hen layings were injected repeatedly with bee venom and phospholipase A2 with Freund's adjuvant. Specific antibody in egg yolk from immunized hen laying was separated, and purified, also immunological characteristics of anti-phospholipase A2 IgY was invested. The results were summarized as follows : 1. Phospholipase A2 was showed single band at molecular weight 17,000 in SDS-PAGE and bee venom was showed two band at molecular weight 17,000 and under molecular weight 6,500 in SDS-PAGE. 2. During 70 days after hen immunized with bee venom and phospholipase A2, antibodies(anti-bee venom IgY to bee venom were showed poor ELISA value in egg yolk, but antibodies(anti-Phospholipase A2 IgY to phospholipase A2 in egg yolk were increased ELISA value from 8 days or 15 days and found maximum ELISA value at 42 days. Also after booster at 49 days, ELISA value of anti-Phospholipase A2 IgY in egg yolk was supported at optical density(O.D 1.0 level, continuously. 3. Titer of phospholipase A2 IgY was showed 1: 32,000. 4. In double immunodiffusion test to phospholipase A2 after double dilution of anti-phospholipase A2 IgY, only precipitation line was made in 1:1 dilution well of anti-Phospholipase A2 IgY. But In immunodiffusion test to anti-phospholipase A2 IgY after double dilution of phospholipase A2, Precipitation line to 250ul/ml well of phospholipase A2 was showed. In double immunodiffusion test to bee venom(1mg/ml after double dilution anti-phospholipase A2 IgY, all well without 1:32 dilution well were showed strong precipitation line. 5. In dot bloting test to anti-phospholipase A2 IgY after diluting bee venom(0.5mg/ml, dot bloting color was showed clearly to 1/100(5㎍/㎖ in bee venom.

  6. Detection of a combination of serum IgG and IgA antibodies against selected mycobacterial targets provides promising diagnostic signatures for active TB.

    Science.gov (United States)

    Awoniyi, Dolapo O; Baumann, Ralf; Chegou, Novel N; Kriel, Belinda; Jacobs, Ruschca; Kidd, Martin; Loxton, Andre G; Kaempfer, Susanne; Singh, Mahavir; Walzl, Gerhard

    2017-06-06

    Immunoglobulin G (IgG) based tests for the diagnosis of active tuberculosis (TB) disease often show a lack of specificity in TB endemic regions, which is mainly due to a high background prevalence of LTBI. Here, we investigated the combined performance of the responses of different Ig classes to selected mycobacterial antigens in primary healthcare clinic attendees with signs and symptoms suggestive of TB. The sensitivity and specificity of IgA, IgG and/or IgM to LAM and 7 mycobacterial protein antigens (ESAT-6, Tpx, PstS1, AlaDH, MPT64, 16kDa and 19kDa) and 2 antigen combinations (TUB, TB-LTBI) in the plasma of 63 individuals who underwent diagnostic work-up for TB after presenting with symptoms and signs compatible with possible active TB were evaluated. Active TB was excluded in 42 individuals of whom 21 has LTBI whereas active TB was confirmed in 21 patients of whom 19 had a follow-up blood draw at the end of 6-month anti-TB treatment. The leading single serodiagnostic markers to differentiate between the presence or absence of active TB were anti-16 kDa IgA, anti-MPT64 IgA with sensitivity and specificity of 90%/90% and 95%/90%, respectively. The combined use of 3 or 4 antibodies further improved this performance to accuracies above 95%. After successful completion of anti-TB treatment at month 6, the levels of 16 kDa IgA and 16 kDa IgM dropped significantly whereas LAM IgG and TB-LTBI IgG increased. These results show the potential of extending investigation of anti-tuberculous IgG responses to include IgM and IgA responses against selected protein and non-protein antigens in differentiating active TB from other respiratory diseases in TB endemic settings.

  7. Design of high productivity antibody capture by protein A chromatography using an integrated experimental and modeling approach.

    Science.gov (United States)

    Ng, Candy K S; Osuna-Sanchez, Hector; Valéry, Eric; Sørensen, Eva; Bracewell, Daniel G

    2012-06-15

    An integrated experimental and modeling approach for the design of high productivity protein A chromatography is presented to maximize productivity in bioproduct manufacture. The approach consists of four steps: (1) small-scale experimentation, (2) model parameter estimation, (3) productivity optimization and (4) model validation with process verification. The integrated use of process experimentation and modeling enables fewer experiments to be performed, and thus minimizes the time and materials required in order to gain process understanding, which is of key importance during process development. The application of the approach is demonstrated for the capture of antibody by a novel silica-based high performance protein A adsorbent named AbSolute. In the example, a series of pulse injections and breakthrough experiments were performed to develop a lumped parameter model, which was then used to find the best design that optimizes the productivity of a batch protein A chromatographic process for human IgG capture. An optimum productivity of 2.9 kg L⁻¹ day⁻¹ for a column of 5mm diameter and 8.5 cm length was predicted, and subsequently verified experimentally, completing the whole process design approach in only 75 person-hours (or approximately 2 weeks). Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Catalytic antibodies in clinical and experimental pathology: human and mouse models.

    Science.gov (United States)

    Ponomarenko, Natalya A; Durova, Oxana M; Vorobiev, Ivan I; Aleksandrova, Elena S; Telegin, Georgy B; Chamborant, Olga G; Sidorik, Lyudmila L; Suchkov, Sergei V; Alekberova, Zemfira S; Gnuchev, Nikolay V; Gabibov, Alexander G

    2002-11-01

    Most of the data accumulated through studies on natural catalytic autoantibodies indicate that production scales up markedly in pathological abnormalities. We have previously described an increased level of DNA-hydrolyzing autoantibodies in the sera of patients with various autoimmune disorders [systemic lupus erythematosus (SLE), rheumatoid arthritis, scleroderma], HIV infection and lymphoproliferative diseases accompanied by autoimmune manifestations. In the present study, we show that an increased level of catalytic activity of autoantibodies can be observed in the sera of autoimmune mice, thus providing a fundamental insight into the medical relevance of abzymes. Polyclonal autoantibodies purified from sera of NZB/W, MRL-lpr/lpr and SJL/J mice show proteolytic and DNA-hydrolyzing activities, as opposed to those harvested from non-autoimmune BALB/c mice. The expressiveness of the catalytic activity was strongly dependent on the age of the animal. The highest levels of catalytic activity were found in the sera of mice aged between 8 and 12 months; the lowest level was typical of younger animals whose age ranged from 6 to 8 weeks. Specific inhibition assays of the catalytic activities were performed to throw light on the nature of the abzyme activity. Within a cohort of aging animals, a strong correlation between marked autoimmune abnormalities and levels of catalytic activities has been established. Nonimmunized SJL/J mice revealed specific immune responses to myelin basic protein (MBP), skeletal muscle myosin (skMyo) and cardiac myosin (Myo), and highly purified antibodies from their serum show specific proteolytic attack against the target antigens. This finding prompted us to undertake a more detailed study of specific antibody-mediated proteolysis in diseased humans. A targeted catalytic response was originally demonstrated against MBP and Myo in multiple sclerosis and myocarditis patients, respectively.

  9. Neutralizing antibody against granulocyte/macrophage colony-stimulating factor inhibits inflammatory response in experimental otitis media.

    Science.gov (United States)

    Kariya, Shin; Okano, Mitsuhiro; Higaki, Takaya; Makihara, Seiichiro; Haruna, Takenori; Eguchi, Motoharu; Nishizaki, Kazunori

    2013-06-01

    Granulocyte/macrophage colony-stimulating factor is important in the pathogenesis of acute and chronic inflammatory disease. We hypothesized that granulocyte/macrophage colony-stimulating factor plays a pivotal role in middle ear inflammation and that neutralization of granulocyte/macrophage colony-stimulating factor would inhibit neutrophil migration into the middle ear and production of inflammatory mediators. Animal experiment. We used transtympanic administration of lipopolysaccharide, a major component of gram-negative bacteria, into mice to induce an experimental otitis media. Control mice received injection of phosphate-buffered saline into the middle ear cavity. Mice were systemically treated with granulocyte/macrophage colony-stimulating factor neutralizing antibody or control immunoglobulin G via intraperitoneal injection 2 hours before transtympanic injection of lipopolysaccharide or phosphate-buffered saline. Middle ear effusions were collected. Concentrations of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, keratinocyte chemoattractant, and macrophage inflammatory protein-2 in middle ear effusions were measured by enzyme-linked immunosorbent assay. Histologic examination of the middle ear was also performed. Transtympanic injection of lipopolysaccharide upregulated levels of granulocyte/macrophage colony-stimulating factor, IL-1β, TNF-α, keratinocyte chemoattractant, and macrophage inflammatory protein-2 in the middle ear. Concentrations of cytokines and chemokines were significantly decreased in mice injected with granulocyte/macrophage colony-stimulating factor neutralizing antibody. Infiltration of inflammatory cells into the middle ear cavity induced by lipopolysaccharide was also significantly reduced by neutralization of granulocyte/macrophage colony-stimulating factor. Systemic injection of granulocyte/macrophage colony-stimulating factor neutralizing antibody inhibits the middle ear inflammation induced by lipopolysaccharide in mice

  10. MuSK induced experimental autoimmune myasthenia gravis does not require IgG1 antibody to MuSK.

    Science.gov (United States)

    Küçükerden, Melike; Huda, Ruksana; Tüzün, Erdem; Yılmaz, Abdullah; Skriapa, Lamprini; Trakas, Nikos; Strait, Richard T; Finkelman, Fred D; Kabadayı, Sevil; Zisimopoulou, Paraskevi; Tzartos, Socrates; Christadoss, Premkumar

    2016-06-15

    Sera of myasthenia gravis (MG) patients with muscle-specific receptor kinase-antibody (MuSK-Ab) predominantly display the non-complement fixing IgG4 isotype. Similarly, mouse IgG1, which is the analog of human IgG4, is the predominant isotype in mice with experimental autoimmune myasthenia gravis (EAMG) induced by MuSK immunization. The present study was performed to determine whether IgG1 anti-MuSK antibody is required for immunized mice to develop EAMG. Results demonstrated a significant correlation between clinical severity of EAMG and levels of MuSK-binding IgG1+, IgG2+ and IgG3+ peripheral blood B cells in MuSK-immunized wild-type (WT) mice. Moreover, MuSK-immunized IgG1 knockout (KO) and WT mice showed similar EAMG severity, serum MuSK-Ab levels, muscle acetylcholine receptor concentrations, neuromuscular junction immunoglobulin and complement deposit ratios. IgG1 and IgG3 were the predominant anti-MuSK isotypes in WT and IgG1 KO mice, respectively. These observations demonstrate that non-IgG1 isotypes can mediate MuSK-EAMG pathogenesis. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Experimental Design and Methods for Development of Diagnostic Assays for Schistosomiasis Using Monoclonal Antibodies.

    Science.gov (United States)

    1983-08-25

    Sera from patients or experimental animals infected with Schistosoma, Fasciola hepatica , Trichinella spiralis, Taenia solium, Echinococcus...infection with T. spiralis (18) or F. hepatica (19), or after immunization with isolated F. hepatica antigens (2023) or P. westermani antigens (17) have a...significantly reduced S. mansoni worm burden: Conversely, mice infected with S. mansoni for over 28 days significantly resisted an F. hepatica

  12. Experimental and in silico modelling analyses of the gene expression pathway for recombinant antibody and by-product production in NS0 cell lines.

    Directory of Open Access Journals (Sweden)

    Emma J Mead

    Full Text Available Monoclonal antibodies are commercially important, high value biotherapeutic drugs used in the treatment of a variety of diseases. These complex molecules consist of two heavy chain and two light chain polypeptides covalently linked by disulphide bonds. They are usually expressed as recombinant proteins from cultured mammalian cells, which are capable of correctly modifying, folding and assembling the polypeptide chains into the native quaternary structure. Such recombinant cell lines often vary in the amounts of product produced and in the heterogeneity of the secreted products. The biological mechanisms of this variation are not fully defined. Here we have utilised experimental and modelling strategies to characterise and define the biology underpinning product heterogeneity in cell lines exhibiting varying antibody expression levels, and then experimentally validated these models. In undertaking these studies we applied and validated biochemical (rate-constant based and engineering (nonlinear models of antibody expression to experimental data from four NS0 cell lines with different IgG4 secretion rates. The models predict that export of the full antibody and its fragments are intrinsically linked, and cannot therefore be manipulated individually at the level of the secretory machinery. Instead, the models highlight strategies for the manipulation at the precursor species level to increase recombinant protein yields in both high and low producing cell lines. The models also highlight cell line specific limitations in the antibody expression pathway.

  13. In vitro experimental 211At-anti-CD33 antibody therapy of leukaemia cells overcomes cellular resistance seen in vivo against gemtuzumab ozogamicin

    International Nuclear Information System (INIS)

    Petrich, Thorsten; Korkmaz, Zekiye; Krull, Doris; Meyer, Geerd J.; Knapp, Wolfram H.; Froemke, Cornelia

    2010-01-01

    Monoclonal anti-CD33 antibodies conjugated with toxic calicheamicin derivative (gemtuzumab ozogamicin, GO) are a novel therapy option for acute myeloid leukaemia (AML). Key prognostic factors for patients with AML are high CD33 expression on the leukaemic cells and the ability to overcome mechanisms of resistance to cytotoxic chemotherapies, including drug efflux or other mechanisms decreasing apoptosis. Alpha particle-emitting radionuclides overwhelm such anti-apoptotic mechanisms by producing numerous DNA double-stranded breaks (DSBs) accompanied by decreased DNA repair. We labelled anti-CD33 antibodies with the alpha-emitter 211 At and compared survival of leukaemic HL-60 and K-562 cells treated with the 211 At-labelled antibodies, GO or unlabelled antibodies as controls. We also measured caspase-3/7 activity, DNA fragmentation and necrosis in HL-60 cells after treatment with the different antibodies or with free 211 At. The mean labelling ratio of 211 At-labelled antibodies was 1:1,090 ± 364 (range: 1:738-1:1,722) in comparison to 2-3:1 for GO. Tumour cell binding of 211 At-anti-CD33 was high in the presence of abundant CD33 expression and could be specifically blocked by unlabelled anti-CD33. 211 At-anti-CD33 decreased survival significantly more than did GO at comparable dilution (1:1,000). No significant differences in induction of apoptosis or necrosis or DNA DSB or in decreased survival were observed after 211 At-anti-CD33 (1:1,090) versus GO (1:1) treatment. Our results suggest that 211 At is a promising, highly cytotoxic radioimmunotherapy in CD33-positive leukaemia and kills tumour cells more efficiently than does calicheamicin-conjugated antibody. Labelling techniques leading to higher chemical yield and specific activities must be developed to increase 211 At-anti-CD33 therapeutic effects. (orig.)

  14. In vitro experimental {sup 211}At-anti-CD33 antibody therapy of leukaemia cells overcomes cellular resistance seen in vivo against gemtuzumab ozogamicin

    Energy Technology Data Exchange (ETDEWEB)

    Petrich, Thorsten; Korkmaz, Zekiye; Krull, Doris; Meyer, Geerd J.; Knapp, Wolfram H. [Hanover University School of Medicine, Department of Nuclear Medicine, Hanover (Germany); Froemke, Cornelia [Hanover University School of Medicine, Department of Biometry, Hanover (Germany)

    2010-05-15

    Monoclonal anti-CD33 antibodies conjugated with toxic calicheamicin derivative (gemtuzumab ozogamicin, GO) are a novel therapy option for acute myeloid leukaemia (AML). Key prognostic factors for patients with AML are high CD33 expression on the leukaemic cells and the ability to overcome mechanisms of resistance to cytotoxic chemotherapies, including drug efflux or other mechanisms decreasing apoptosis. Alpha particle-emitting radionuclides overwhelm such anti-apoptotic mechanisms by producing numerous DNA double-stranded breaks (DSBs) accompanied by decreased DNA repair. We labelled anti-CD33 antibodies with the alpha-emitter {sup 211}At and compared survival of leukaemic HL-60 and K-562 cells treated with the {sup 211}At-labelled antibodies, GO or unlabelled antibodies as controls. We also measured caspase-3/7 activity, DNA fragmentation and necrosis in HL-60 cells after treatment with the different antibodies or with free {sup 211}At. The mean labelling ratio of {sup 211}At-labelled antibodies was 1:1,090 {+-} 364 (range: 1:738-1:1,722) in comparison to 2-3:1 for GO. Tumour cell binding of {sup 211}At-anti-CD33 was high in the presence of abundant CD33 expression and could be specifically blocked by unlabelled anti-CD33. {sup 211}At-anti-CD33 decreased survival significantly more than did GO at comparable dilution (1:1,000). No significant differences in induction of apoptosis or necrosis or DNA DSB or in decreased survival were observed after {sup 211}At-anti-CD33 (1:1,090) versus GO (1:1) treatment. Our results suggest that {sup 211}At is a promising, highly cytotoxic radioimmunotherapy in CD33-positive leukaemia and kills tumour cells more efficiently than does calicheamicin-conjugated antibody. Labelling techniques leading to higher chemical yield and specific activities must be developed to increase {sup 211}At-anti-CD33 therapeutic effects. (orig.)

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  16. Theoretical and experimental fundamentals of designing promising technological equipment to improve efficiency and environmental safety of highly viscous oil recovery from deep oil reservoirs

    Science.gov (United States)

    Moiseyev, V. A.; Nazarov, V. P.; Zhuravlev, V. Y.; Zhuykov, D. A.; Kubrikov, M. V.; Klokotov, Y. N.

    2016-12-01

    The development of new technological equipment for the implementation of highly effective methods of recovering highly viscous oil from deep reservoirs is an important scientific and technical challenge. Thermal recovery methods are promising approaches to solving the problem. It is necessary to carry out theoretical and experimental research aimed at developing oil-well tubing (OWT) with composite heatinsulating coatings on the basis of basalt and glass fibers. We used the method of finite element analysis in Nastran software, which implements complex scientific and engineering calculations, including the calculation of the stress-strain state of mechanical systems, the solution of problems of heat transfer, the study of nonlinear static, the dynamic transient analysis of frequency characteristics, etc. As a result, we obtained a mathematical model of thermal conductivity which describes the steady-state temperature and changes in the fibrous highly porous material with the heat loss by Stefan-Boltzmann's radiation. It has been performed for the first time using the method of computer modeling in Nastran software environments. The results give grounds for further implementation of the real design of the OWT when implementing thermal methods for increasing the rates of oil production and mitigating environmental impacts.

  17. The time course of the specific antibody response by various ELISAs in pigs experimentally infected with Toxoplasma gondii

    DEFF Research Database (Denmark)

    Lind, Peter; Haugegaard, J.; Wingstrand, Anne

    1997-01-01

    With the aim of developing routine serological tests for monitoring the Toxoplasma infection status of Danish swine herds, four ELISAs based on tachyzoite antigen were set up: (1) an indirect ELISA for IgG-antibody; (2) a blocking ELISA for antibody to the membrane antigen, P-30; (3) an indirect ...

  18. The time course of the specific antibody response by various ELISAs in pigs experimentally infected with Toxoplasma gondii

    DEFF Research Database (Denmark)

    Lind, Peter; Haugegaard, J.; Wingstrand, Anne

    1997-01-01

    With the aim of developing routine serological tests for monitoring the Toxoplasma infection status of Danish swine herds, four ELISAs based on tachyzoite antigen were set up: (1) an indirect ELISA for IgG-antibody; (2) a blocking ELISA for antibody to the membrane antigen, P-30; (3) an indirect...

  19. An experimental test of stroke recovery by implanting a hyaluronic acid hydrogel carrying a Nogo receptor antibody in a rat model

    Energy Technology Data Exchange (ETDEWEB)

    Ma Jun [Biomaterials Laboratory, Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Tian Weiming [Biomaterials Laboratory, Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Hou Shaoping [Beijing Institute of Neuroscience, Capital University of Medical Sciences, Beijing 100054 (China); Xu Qunyuan [Beijing Institute of Neuroscience, Capital University of Medical Sciences, Beijing 100054 (China); Spector, Myron [Tissue Engineering, VA Boston Healthcare System, Harvard Medical School, Boston, MA (United States); Cui Fuzhai [Biomaterials Laboratory, Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China)

    2007-12-15

    The objective of the study was to determine the effects of a hyaluronic-acid-based (HA-based) hydrogel implant, carrying a polyclonal antibody to the Nogo-66 receptor (NgR), on adult rats that underwent middle cerebral artery occlusion (MCAO). Behavioral tests of a forelimb-reaching task suggested that the disabled function of the impaired forelimb in this stroke model was ameliorated by the implant to a certain extent. These behavioral findings were correlated with immunohistochemical results of investigating the distribution of NgR antibody, neurofilaments (NF) and neuron-specific class III {beta}-tubulin (TuJ1) in the brain sections. The porous hydrogel functioned as a scaffold to deliver the NgR antibody, support cell migration and development. In addition, it was found NF-positive and TuJ1-positive expressions were distributed in the implanted hydrogel. Collectively, the results demonstrate the promise of the HA hydrogel as a scaffold material and the delivery vehicle of the NgR antibody for the repair of defects and the support of neural regeneration in the brain.

  20. IgM but not IgG monoclonal anti-Nocardia brasiliensis antibodies confer protection against experimental actinomycetoma in BALB/c mice.

    Science.gov (United States)

    Gonzalez-Suarez, Maria L; Salinas-Carmona, Mario C; Pérez-Rivera, Isabel

    2009-10-01

    Nocardia brasiliensis is a facultative intracellular microorganism that produces a human chronic infection known as actinomycetoma. Human and mouse anti-N. brasiliensis antibody response identify P24, P26 and P61 immunodominant antigens. In this work, we generated immunoglobulin M (IgM) and IgG monoclonal antibodies (mAbs) specific to immunodominant P61 antigen. The monoclonal IgM (NbM1) and IgG2a (NbG1) antibodies were assessed for their in vitro bactericidal activity, in vivo protective effect and ability to block catalase activity. These mAbs specifically recognized P61, but they did not inhibit its enzyme activity. The in vitro bactericidal effect of NbG1 was higher than the killing ability of the IgM mAb. In vivo experiments with a murine model of experimental infection with N. brasiliensis injected into rear footpads was used to test the effect of NbM1 and NbG1. The negative untreated group developed a chronic actinomycetoma within 4 weeks. IgM mAbs conferred protection to BALB/c mice infected with N. brasiliensis. IgG mAb lacked this protective effect. IgM mAb showed a dose-response correlation between antibody concentration and lesion size. These results demonstrate that humoral immune response mediated by antigen-specific IgM antibody protects against an intracellular bacterial infection.

  1. Anti-S-nitrosocysteine antibodies are a predictive marker for demyelination in experimental autoimmune encephalomyelitis: implications for multiple sclerosis.

    Science.gov (United States)

    Boullerne, Anne I; Rodriguez, Jose J; Touil, Tarik; Brochet, Bruno; Schmidt, Stephan; Abrous, Nora D; Le Moal, Michel; Pua, Jeffrey R; Jensen, Mark A; Mayo, Willy; Arnason, Barry G W; Petry, Klaus G

    2002-01-01

    Multiple sclerosis (MS) is characterized by inflammation within the CNS. This inflammatory response is associated with production of nitric oxide (NO) and NO-related species that nitrosylate thiols. We postulated that MS patients would exhibit an antibody (Ab) response directed against proteins containing S-nitrosocysteine (SNO-cysteine) and showed that anti-NO-cysteine Abs of the IgM isotype are in fact present in the sera of some MS patients (Boullerne et al., 1995). We report here the presence of a seemingly identical Ab response directed against SNO-cysteine in an acute model of MS, experimental autoimmune encephalomyelitis (EAE) induced in Lewis rats with the 68-84 peptide of guinea pig myelin basic protein (MBP(68-84)). Serum levels of anti-SNO-cysteine Abs peaked 1 week before the onset of clinical signs and well before the appearance of anti-MBP(68-84) Abs. The anti-SNO-cysteine Ab peak titer correlated with the extent of subsequent CNS demyelination, suggesting a link between Ab level and CNS lesion formation. In relapsing-remitting MS patients, we found elevated anti-SNO-cysteine Ab at times of relapse and normal values in most patients judged to be in remission. Two-thirds of patients with secondary progressive MS had elevated anti-SNO-cysteine Ab levels, including those receiving interferon beta-1b. The data show that a rise in circulating anti-SNO-cysteine Ab levels precedes onset of EAE. Anti-SNO-cysteine Abs are also elevated at times of MS attacks and in progressive disease, suggesting a possible role for these Abs, measurable in blood, as a biological marker for clinical activity.

  2. Impact of Infection Dose and Previous Serum Antibodies against the Locus of Enterocyte Effacement Proteins on Escherichia coli O157:H7 Shedding in Calves following Experimental Infection

    Directory of Open Access Journals (Sweden)

    L. Martorelli

    2015-01-01

    Full Text Available Escherichia coli O157:H7 is the main causative agent of haemolytic uremic syndrome. Cattle are the main reservoir of these bacteria, and have been shown to develop immune response to colonization. Our aim was to investigate the faecal shedding pattern of E. coli O157:H7 in calves challenged intragastrically with either 108 or 1010 CFU, as well as the ability of specific preexisting antibodies to reduce shedding of the pathogen. Shedding was analysed by direct counting as well as enrichment of rectoanal mucosal swabs. Statistical analysis was performed using a linear model for repeated measures with and without the inclusion of preexisting antibodies against the carboxy-terminal fraction of intimin-γ (γ-intimin C280 as a covariable. Results suggest that there is a statistical difference in the area under the shedding curves between both doses for 14 as well as 28 days after challenge (p = 0.0069 and 0.0209, resp.. This difference is increased when the prechallenge antibodies are taken into account (p = 0.0056 and 0.0185. We concluded that the bacterial dose influences shedding on calves experimentally challenged and that preexisting antibodies against E. coli O157:H7 γ-intimin C280 could partially reduce faecal excretion.

  3. 99mTc-annexin V and 111In-antimyosin antibody uptake in experimental myocardial infarction in rats

    International Nuclear Information System (INIS)

    Sarda-Mantel, Laure; Rouzet, Francois; Martet, Genevieve; Raguin, Olivier; Vrigneaud, Jean-Marc; Guludec, Dominique Le; Michel, Jean-Baptiste; Louedec, Liliane; Vanderheyden, Jean-Luc; Hervatin, Florence; Khaw, Ban An

    2006-01-01

    99m Tc-annexin V (ANX) allows scintigraphic detection of apoptotic cells via specific binding to exposed phosphatidylserine. In myocardial infarction, apoptosis of myocytes is variable and depends especially on the presence or absence of coronary reperfusion. In this study, ANX uptake in non-reperfused experimental myocardial infarcts was compared with uptake of a marker of myocyte necrosis ( 111 In-antimyosin antibodies, AM) and an immunohistochemical marker of apoptosis (Apostain). The left anterior coronary artery was ligated in 47 Wistar rats, which were then injected with ANX (n=20), AM (n=21) or both (n=6). Myocardial uptake of ANX and AM was determined at 2 h (n=14), 4 h (n=14) and 24 h (n=19) after coronary ligation (CL), by quantitative autoradiography with (n=23) or without (n=24) gamma imaging. Heart-to-lung ratios (HLRs) and infarct-to-remote myocardium activity ratios (INRs) were calculated on the scintigrams and autoradiograms respectively. Cardiac sections were stained with haematoxylin-eosin and Apostain. The above studies were repeated in 12 normal rats. All rats with CL showed increased ANX and AM uptake in cardiac areas on scintigrams 24 h after CL, with HLRs higher than in controls: 3.1±0.6 versus 1.5±0.3 (p=0.001) for ANX and 1.99±0.44 versus 1.01±0.05 (p<0.0005) for AM. Autoradiography showed intense ANX and AM uptake in infarcts, with comparable topography and INRs at 2 h, 4 h and 24 h after CL (4.6±0.9 versus 5.0±1.8 at 24 h), while Apostain staining was very low (0.06±0.06% of cells). In this model of persistent CL, we observed increased ANX uptake in injured myocardium, comparable in intensity, topography and kinetics to that of AM. There was only minimal Apostain staining in the same areas. (orig.)

  4. Antibody response and maternal immunity upon boosting PRRSV-immune sows with experimental farm-specific and commercial PRRSV vaccines.

    Science.gov (United States)

    Geldhof, Marc F; Van Breedam, Wander; De Jong, Ellen; Lopez Rodriguez, Alfonso; Karniychuk, Uladzimir U; Vanhee, Merijn; Van Doorsselaere, Jan; Maes, Dominiek; Nauwynck, Hans J

    2013-12-27

    The porcine reproductive and respiratory syndrome virus (PRRSV) causes reproductive failure in sows and respiratory disease in pigs of all ages. Despite the frequent use of vaccines to maintain PRRSV immunity in sows, little is known on how the currently used vaccines affect the immunity against currently circulating and genetically divergent PRRSV variants in PRRSV-immune sows, i.e. sows that have a pre-existing PRRSV-specific immunity due to previous infection with or vaccination against the virus. Therefore, this study aimed to assess the capacity of commercially available attenuated/inactivated PRRSV vaccines and autogenous inactivated PRRSV vaccines - prepared according to a previously optimized in-house protocol - to boost the antibody immunity against currently circulating PRRSV variants in PRRSV-immune sows. PRRSV isolates were obtained from 3 different swine herds experiencing PRRSV-related problems, despite regular vaccination of gilts and sows against the virus. In a first part of the study, the PRRSV-specific antibody response upon booster vaccination with commercial PRRSV vaccines and inactivated farm-specific PRRSV vaccines was evaluated in PRRSV-immune, non-pregnant replacement sows from the 3 herds. A boost in virus-neutralizing antibodies against the farm-specific isolate was observed in all sow groups vaccinated with the corresponding farm-specific inactivated vaccines. Use of the commercial attenuated EU type vaccine boosted neutralizing antibodies against the farm-specific isolate in sows derived from 2 farms, while use of the commercial attenuated NA type vaccine did not boost farm-specific virus-neutralizing antibodies in any of the sow groups. Interestingly, the commercial inactivated EU type vaccine boosted farm-specific virus-neutralizing antibodies in sows from 1 farm. In the second part of the study, a field trial was performed at one of the farms to evaluate the booster effect of an inactivated farm-specific vaccine and a commercial

  5. IgG antibody response against salivary gland antigens from Oestrus ovis L. larvae (Diptera: Oestridae) in experimentally and naturally infected goats.

    Science.gov (United States)

    Angulo-Valadez, C E; Cepeda-Palacios, R; Ascencio, F; Jacquiet, Ph; Dorchies, Ph; Ramírez-Orduña, J M; López, M A

    2009-05-12

    The aims of this study were to analyze the systemic IgG responses against third-instar salivary gland (L3SG) antigens by ELISA in Oestrus ovis experimentally infected kids (EIK) and in naturally exposed adult goats (NEG). Firstly, kids (n=4 per group) were assigned to receive intranasally 0, 12, 24, 36, and 48 first-instars in experimental infections. Blood samples were taken from EIK at Days 0, 14, 42 and 67 post-infection. At necropsy (Day 67), larval number and developmental instars were recorded. In an epidemiological study, blood serum samples were collected from 448 grazing NEG (n=20 flocks) in Baja California Sur, Mexico. Results showed that larval establishment rate was similar in EIK groups. Systemic IgG response reached the threshold after Day 42, but humoral response was not statistically different among EIK groups receiving experimental infections. In NEG, all surveyed flocks (100%) showed specific systemic IgG antibodies to L3SG antigens and the overall goat oestrosis prevalence was 59.2%. In conclusion, larval L3SG antigens were effective in detection of specific systemic IgG antibodies against O. ovis infected kids and goats by ELISA.

  6. Antibody Responses of Cervids (Cervus elaphus) following Experimental Mycobacterium bovis Infection and the Implications for Immunodiagnosis ▿

    OpenAIRE

    Harrington, Noel P.; Surujballi, Om P.; Prescott, John F.; Duncan, J. Robert; Waters, W. Ray; Lyashchenko, Konstantin; Greenwald, Rena

    2008-01-01

    Captive and free-ranging wildlife animals are implicated in the maintenance and transmission of bovine tuberculosis and therefore pose a significant obstacle to eradication of the disease from domestic livestock. The current antemortem diagnostic method, the intradermal tuberculin skin test, is impractical for routine use with many wild animals. Antibody-based assays are particularly attractive because the animals are handled only once and immediate processing of the sample is not required. T...

  7. DETECTION OF ANTIBODIES TO CANDIDA ALBICANS GERM TUBE BY IMMUNOFLUORESCENCE IN IMMUNOSUPPRESSED MICE WITH EXPERIMENTAL SYSTEMIC CANDIDIASIS

    Directory of Open Access Journals (Sweden)

    F. Zaini

    2007-07-01

    Full Text Available "nThe increasing incidence of systemic candidiasis, which parallels the use of invasive and immunosuppressive medical procedures, necessitates development of rapid and cost effective tests for diagnosis of systemic candidiasis. Therefore in this study 85 mice were first immunosuppressed by cyclophosphamide and then infected by Candida albicans NCPF 3153. Other 85 mice were employed as control. The case and control mice were bled and then autopsied. Hearts and kidneys were checked by direct, histopathological and cultural examination for systemic candidiasis. The 85 sera from histological proven cases and 85 control mice were adsorbed with heat killed blastospores of same strain of C. albicans. Anti-Candida albicans germ tube antibodies were detected by indirect immunofluorescence assay for diagnosis of invasive candidiasis in case and control mice. In addition, sera from 35 mice with proven cryptococcosis were also tested. While 84 mice with proven systemic candidiasis (100% had anti-germ tube antibodies, these antibodies were absent in all controls and mice with cryptococcosis. The specificity was 100%, indicating a high degree of discrimination was possible between systemic candidiasis and cryptococcosis in the mice studied. It must be concluded that anti-germ tube responses did not appear to be significantly reduced in immunocompromised mice.

  8. Continuing experimental investigations with radiolabeled anti-collagen antibodies and related antibodies: Progress report, May 1, 1987 through November 30, 1987

    International Nuclear Information System (INIS)

    Gottschalk, A.

    1987-01-01

    The basic research goal is to develop an in vivo probe with histopathologic correlates that can be used to characterize irradiation lung injury. Irradiation lung injury is a very important problem in patients receiving total body irradiation prior to bone marrow transplantation for diseases such as leukemia. Basic research defining irradiation lung injury will have important clinical significance. We have developed a simple jig to hold the Sprague-Dawley rat during irradiation, and have successfully shielded all but the right lung. Dosimetry studies were performed and we found that we were delivering a dose to the rats mid-lung of 1 Gy/min from the experimental therapy machine. We confirmed the region of pulmonary irradiation not only with radiographic studies of the jig in place, but also with injections of technetium-labeled-MASS in some of our 25-day rats. This showed a profound perfusion deficit compatible with irradiation involving the entire right lung confirming successful placement of the irradiation portal. All of the experiments we describe employed a dose of 25 Gy. 1 fig., 3 tabs

  9. Enhanced attenuation of meningeal inflammation and brain edema by concomitant administration of anti-CD18 monoclonal antibodies and dexamethasone in experimental Haemophilus meningitis.

    Science.gov (United States)

    Sáez-Llorens, X; Jafari, H S; Severien, C; Parras, F; Olsen, K D; Hansen, E J; Singer, I I; McCracken, G H

    1991-12-01

    Antiinflammatory therapy has been shown to reduce the adverse pathophysiological consequences that occur in bacterial meningitis and to improve outcome from disease. In the present study, modulation of two principal steps of the meningeal inflammatory cascade was accomplished by concomitant administration of dexamethasone to diminish overproduction of cytokines in response to a bacterial stimulus and of a monoclonal antibody directed against adhesion-promoting receptors on leukocytes to inhibit recruitment of white blood cells into the subarachnoid space. Dexamethasone and antibody therapy produced a marked attenuation of all indices of meningeal inflammation and reduction of brain water accumulation after H. influenzae-induced meningitis in rabbits compared with results of each agent given alone and of untreated animals. In addition, the enhanced host's meningeal inflammatory reaction that follows antibiotic-induced bacterial lysis was profoundly ameliorated when dual therapy was administered without affecting clearance rates of bacteria from cerebrospinal fluid and vascular compartments. The combination of both therapeutic approaches may offer a promising mode of treatment to improve further the outcome from bacterial meningitis.

  10. Early detection and longitudinal monitoring of experimental primary and disseminated melanoma using [{sup 18}F]ICF01006, a highly promising melanoma PET tracer

    Energy Technology Data Exchange (ETDEWEB)

    Rbah-Vidal, Latifa; Vidal, Aurelien; Besse, Sophie; Audin, Laurent; Degoul, Francoise; Miot-Noirault, Elisabeth; Moins, Nicole; Auzeloux, Philippe; Chezal, Jean-Michel [Clermont Universite, Universite d' Auvergne, Imagerie Moleculaire et Therapie Vectorisee, BP 10448, Clermont-Ferrand (France); Inserm, U 990, Clermont-Ferrand (France); Cachin, Florent [Clermont Universite, Universite d' Auvergne, Imagerie Moleculaire et Therapie Vectorisee, BP 10448, Clermont-Ferrand (France); Inserm, U 990, Clermont-Ferrand (France); Centre Jean Perrin, Clermont-Ferrand (France); Bonnet, Mathilde [U1071 INSERM-Universite d' Auvergne, M2USH, Clermont-Ferrand (France); Askienazy, Serge [CYCLOPHARMA Laboratories, Biopole Clermont-Limagne, Saint-Beauzire (France); Dolle, Frederic [CEA, I2BM, Service Hospitalier Frederic Joliot, Orsay (France)

    2012-09-15

    Here, we report a new and rapid radiosynthesis of {sup 18}F-N-[2-(diethylamino)ethyl]-6-fluoro-pyridine-3-carboxamide ([{sup 18}F]ICF01006), a molecule with a high specificity for melanotic tissue, and its evaluation in a murine model for early specific detection of pigmented primary and disseminated melanoma. [{sup 18}F]ICF01006 was synthesized using a new one-step bromine-for-fluorine nucleophilic heteroaromatic substitution. Melanoma models were induced by subcutaneous (primary tumour) or intravenous (lung colonies) injection of B16BL6 melanoma cells in C57BL/6J mice. The relevance and sensitivity of positron emission tomography (PET) imaging using [{sup 18}F]ICF01006 were evaluated at different stages of tumoural growth and compared to {sup 18}F-fluorodeoxyglucose ([{sup 18}F]FDG). The fully automated radiosynthesis of [{sup 18}F]ICF01006 led to a radiochemical yield of 61 % and a radiochemical purity >99 % (specific activity 70-80 GBq/{mu}mol; total synthesis time 42 min). Tumours were visualized before they were palpable as early as 1 h post-injection with [{sup 18}F]ICF01006 tumoural uptake of 1.64 {+-} 0.57, 3.40 {+-} 1.47 and 11.44 {+-} 2.67 percentage of injected dose per gram of tissue (%ID/g) at days 3, 5 and 14, respectively. [{sup 18}F]ICF01006 PET imaging also allowed detection of melanoma pulmonary colonies from day 9 after tumour cell inoculation, with a lung radiotracer accumulation correlated with melanoma invasion. At day 21, radioactivity uptake in lungs reached a value of 5.23 {+-} 2.08 %ID/g (versus 0.41 {+-} 0.90 %ID/g in control mice). In the two models, comparison with [{sup 18}F]FDG showed that both radiotracers were able to detect melanoma lesions, but [{sup 18}F]ICF01006 was superior in terms of contrast and specificity. Our promising results provide further preclinical data, reinforcing the excellent potential of [{sup 18}F]ICF01006 PET imaging for early specific diagnosis and follow-up of melanin-positive disseminated melanoma. (orig.)

  11. Early detection and longitudinal monitoring of experimental primary and disseminated melanoma using [18F]ICF01006, a highly promising melanoma PET tracer

    International Nuclear Information System (INIS)

    Rbah-Vidal, Latifa; Vidal, Aurelien; Besse, Sophie; Audin, Laurent; Degoul, Francoise; Miot-Noirault, Elisabeth; Moins, Nicole; Auzeloux, Philippe; Chezal, Jean-Michel; Cachin, Florent; Bonnet, Mathilde; Askienazy, Serge; Dolle, Frederic

    2012-01-01

    Here, we report a new and rapid radiosynthesis of 18 F-N-[2-(diethylamino)ethyl]-6-fluoro-pyridine-3-carboxamide ([ 18 F]ICF01006), a molecule with a high specificity for melanotic tissue, and its evaluation in a murine model for early specific detection of pigmented primary and disseminated melanoma. [ 18 F]ICF01006 was synthesized using a new one-step bromine-for-fluorine nucleophilic heteroaromatic substitution. Melanoma models were induced by subcutaneous (primary tumour) or intravenous (lung colonies) injection of B16BL6 melanoma cells in C57BL/6J mice. The relevance and sensitivity of positron emission tomography (PET) imaging using [ 18 F]ICF01006 were evaluated at different stages of tumoural growth and compared to 18 F-fluorodeoxyglucose ([ 18 F]FDG). The fully automated radiosynthesis of [ 18 F]ICF01006 led to a radiochemical yield of 61 % and a radiochemical purity >99 % (specific activity 70-80 GBq/μmol; total synthesis time 42 min). Tumours were visualized before they were palpable as early as 1 h post-injection with [ 18 F]ICF01006 tumoural uptake of 1.64 ± 0.57, 3.40 ± 1.47 and 11.44 ± 2.67 percentage of injected dose per gram of tissue (%ID/g) at days 3, 5 and 14, respectively. [ 18 F]ICF01006 PET imaging also allowed detection of melanoma pulmonary colonies from day 9 after tumour cell inoculation, with a lung radiotracer accumulation correlated with melanoma invasion. At day 21, radioactivity uptake in lungs reached a value of 5.23 ± 2.08 %ID/g (versus 0.41 ± 0.90 %ID/g in control mice). In the two models, comparison with [ 18 F]FDG showed that both radiotracers were able to detect melanoma lesions, but [ 18 F]ICF01006 was superior in terms of contrast and specificity. Our promising results provide further preclinical data, reinforcing the excellent potential of [ 18 F]ICF01006 PET imaging for early specific diagnosis and follow-up of melanin-positive disseminated melanoma. (orig.)

  12. A combined theoretical and experimental study on the oxygenated graphitic carbon nitride as a promising sulfur host for lithium-sulfur batteries

    Science.gov (United States)

    He, Feng; Li, Kai; Yin, Cong; Ding, Yingchun; Tang, Hao; Wang, Ying; Wu, Zhijian

    2018-01-01

    To effectively restrain the dissolution of soluble polysulfides and fully utilize the active sulfur materials in lithium-sulfur (Li-S) batteries, host materials with unique compositions and porous structures have been pursued. Herein, we have investigated the mechanism of the excellent activity of oxygenated g-C3N4 for Li-S batteries from theoretical perspective, and the further experiment confirms that our O-g-C3N4-S cathode exhibits much better electrochemical performance compared with those in previous reports. Our DFT calculations reveal that the oxygenated material has better electrical conductivity and stronger adsorption ability with the Li2Sx species compared with the pristine g-C3N4 and other two-dimensional (2D) materials. Furthermore, we have confirmed experimentally that the O-g-C3N4-S composite cathode exhibits excellent electrochemical performance in Li-S batteries with high reversible discharge capacity of 1030 mAh g-1 after 100 cycles at 0.2 C, great rate capability with the discharge capacity of 364 mAh g-1 even at 5.0 C, and outstanding long-term cyclic stability with the discharge capacity of 465 mAh g-1 after 1000 cycles at 1.0 C (capacity decay was only 0.046% per cycle). Our results also suggest that theoretical study will play a significant role in predicting and screening novel materials with better performance.

  13. Mesalazine-probiotics beads for acetic acid experimental colitis: formulation and characterization of a promising new therapeutic strategy for ulcerative colitis.

    Science.gov (United States)

    Vishwakarma, Neelam; Ganeshpurkar, Aditya; Pandey, Vikas; Dubey, Nazneen; Bansal, Divya

    2015-01-01

    Acetic acid ulcerative colitis (UC) is an experimental condition created due to intra-rectal administration of acetic acid which causes inflammation and ulceration in the lining of colon and rectum. In such condition, the colon cannot absorb liquid from the stools, resulting in larger volume of watery stools. Mesalazine is mainly used for the treatment of UC but suffers from the drawback of having poor bioavailability. UC is also characterized by alteration in colonic microflora. The present work was focused on delivering mesalazine along with probiotic, which would facilitate to refurbish customary growth of microflora. Mesalazine and probiotic were encapsulated in pectin beads with an aim to protect the drug from gastric environment and target to colonic region. Pectin beads were prepared, formulation process was optimized for polymer concentration, drug concentration, cross-linking agent concentration. Formulation was characterized for surface morphology, in vitro drug release studies, determination of viable cell count, in vivo ulcer protective studies and stability studies. Average particle diameter of beads was ∼1.44-1.72 mm. Drug entrapment efficiency was found to be optimal (78-79%). A sustained release of drug was observed for 5 h; nearly 60% of drug was released at the end of 10 h. Microbiological studies of probiotic showed best cell viability. In acetic acid induced UC model, Mesalazine-probiotic beads-treated group showed significant (p probiotic loaded beads may serve as a useful colon specific drug delivery system for treatment of colitis.

  14. Treatment with anti-interferon-gamma monoclonal antibodies modifies experimental autoimmune encephalomyelitis in interferon-gamma receptor knockout mice

    DEFF Research Database (Denmark)

    Espejo, C; Penkowa, M; Sáez-Torres, I

    2001-01-01

    antibodies (mAb) on day 8 postimmunization. Clinical scoring and both histological and immunohistochemical studies were undertaken for all groups. We hereby show that treatment with anti-IFN-gamma mAb worsened the disease course of 129Sv wild-type mice. However, it decreased the mean daily score in IFN......-gamma R(-/-) 129Sv and the incidence of the disease down to 50% in C57Bl/6x129Sv IFN-gamma R(-/-) mice. Moreover, after anti-IFN-gamma mAb treatment, oxidative stress levels, metallothionein I and II antioxidant protein expression, and apoptoticneuronal death were increased in wild-type mice while......(-/-)) mouse types: C57Bl/6x129Sv, with a disruption of the IFN-gamma receptor cytoplasmic domain, and 129Sv, homozygous for a disrupted IFN-gamma receptor gene. Mice were immunized with peptide 40-55 from rat myelin oligodendrocyte glycoprotein. A subgroup of mice was treated with anti-IFN-gamma monoclonal...

  15. Humanized Antibodies for Antiviral Therapy

    Science.gov (United States)

    Co, Man Sung; Deschamps, Marguerite; Whitley, Richard J.; Queen, Cary

    1991-04-01

    Antibody therapy holds great promise for the treatment of cancer, autoimmune disorders, and viral infections. Murine monoclonal antibodies are relatively easy to produce but are severely restricted for therapeutic use by their immunogenicity in humans. Production of human monoclonal antibodies has been problematic. Humanized antibodies can be generated by introducing the six hypervariable regions from the heavy and light chains of a murine antibody into a human framework sequence and combining it with human constant regions. We humanized, with the aid of computer modeling, two murine monoclonal antibodies against herpes simplex virus gB and gD glycoproteins. The binding, virus neutralization, and cell protection results all indicate that both humanized antibodies have retained the binding activities and the biological properties of the murine monoclonal antibodies.

  16. Experimental validation of multi-epitope peptides including promising MHC class I- and class II-restricted epitopes of four known Leishmania infantum proteins

    Directory of Open Access Journals (Sweden)

    Maria eAgallou

    2014-06-01

    Full Text Available Leishmaniasis is a significant worldwide health problem for which no vaccine exists. Activation of CD4+ and CD8+ T cells is crucial for the generation of protective immunity against parasite. Recent trend in vaccine design has been shifted to epitope-based vaccines that are more specific, safe, and easy to produce. In the present study, four known antigenic Leishmania (L. infantum proteins, CPA, histone H1, KMP-11 and LeIF were analysed for the prediction of binding epitopes to H2d MHC class I and class II molecules, using online available algorithms. Based on in silico analysis, eight peptides including highly scored MHC class I- and class II-restricted epitopes were synthesized. Peptide immunogenicity was validated in MHC compatible BALB/c mice immunized with each synthetic peptide emulsified in CFA/IFA. CPA_p2, CPA_p3, H1_p1 and LeIF_p6 induced strong spleen cell proliferation upon in vitro peptide re-stimulation. In addition, the majority of the peptides, except of LeIF_p1 and KMP-11_p1, induced IFN-γ secretion, while KMP-11_p1 indicated a suppressive effect on IL-10 production. CPA_p2, CPA_p3, LeIF_p3 and LeIF_p6 induced IFN-γ-producing CD4+ T cells indicating a TH1 type response. In addition, CPA_p2, CPA_p3 and H1_p1 induced also the induction of CD8+ T cells. The induction of peptide-specific IgG in immunized mice designated also the existence of B cell epitopes in peptide sequences. Combining immunoinformatic tools and experimental validation, we demonstrated that CPA_p2, CPA_p3, H1_p1, H1_p3, CPA_p2, LeIF_p3 and LeIF_p6 are likely to include potential epitopes for the induction of protective cytotoxic and/or TH1-type immune responses supporting the feasibility of peptide-based vaccine development for leishmaniasis.

  17. Age-dependent differences in cytokine and antibody responses after experimental RSV infection in a bovine model

    DEFF Research Database (Denmark)

    Grell, S.N.; Riber, Ulla; Tjørnehøj, Kirsten

    2005-01-01

    Respiratory syncytial virus (RSV) causes severe respiratory disease in both infants and calves. As in humans, bovine RSV (BRSV) infections are most severe in the first 6 months of life. In this study, experimental infection with BRSV was performed in calves aged 1-5, 9-16 or 32-37 weeks. Compared...... "inflammatory" but weak humoral antiviral response in very young animals suggests that enhanced inflammation contributes to disease during RSV infection during the early postnatal period....

  18. An animal model of pain produced by systemic administration of an immunotherapeutic anti-ganglioside antibody

    NARCIS (Netherlands)

    Slart, R.; Yu, A L; Yaksh, T L; Sorkin, L S

    For the management of pediatric neuroblastoma, a promising experimental treatment includes slow systemic infusion of a human/mouse chimeric monoclonal antibody against the GD2 ganglioside. Beneficial actions are however, accompanied by severe pain and altered cardiovascular tone. The pain is

  19. 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...

  20. Elicited vs. voluntary promises

    NARCIS (Netherlands)

    Ismayilov, H.; Potters, Jan

    2017-01-01

    We set up an experiment with pre-play communication to study the impact of promise elicitation by trustors from trustees on trust and trustworthiness. When given the opportunity a majority of trustors solicits a promise from the trustee. This drives up the promise making rate by trustees to almost

  1. A monoclonal antibody to alpha 4-integrin reverses the MR-detectable signs of experimental allergic encephalomyelitis in the guinea pig.

    Science.gov (United States)

    Kent, S J; Karlik, S J; Rice, G P; Horner, H C

    1995-01-01

    Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune disease of the CNS characterized by blood-brain barrier breakdown, cerebral edema formation, lymphocyte infiltration, and demyelination, and is used as an animal model of multiple sclerosis (MS). MR imaging is important for the diagnosis of MS and for the evaluation of potential new therapies. In this study, T2-weighted and T1-weighted contrast-enhanced MR imaging was used to evaluate the effectiveness of an antiadhesion therapy in EAE. Leukocyte-endothelial adhesion at the blood-brain barrier is considered an essential step in the mediation of CNS leukocyte infiltration in EAE. AN100226m, a monoclonal antibody to alpha 4 integrin has been previously shown to reverse the clinical and histologic signs of EAE by blocking this interaction. In the present study, AN100226m treatment in acute EAE significantly decreased contrast enhancement of the CNS parenchyma indicating closure of the blood-brain barrier. The percentage of pixels due to leakage of contrast material in T1-weighted images decreased to < 4% in AN100226m-treated animals whereas it was increased to 15% in control animals (P < .05, Mann-Whitney rank sum test). A decrease in CNS abnormalities associated with cerebral edema and inflammation was also observed on T2-weighted images (P < .05, Mann-Whitney rank sum test). Thus, an antibody to alpha 4 integrin reversed the blood-brain barrier permeability changes characteristic of acute EAE. In addition, the further accumulation of inflammatory edema was prevented and preexisting edema was resolved.

  2. Clinical evaluation and antibody responses in sheep after primary and secondary experimental challenges with the mange mite Sarcoptes scabiei var. ovis.

    Science.gov (United States)

    Rodríguez-Cadenas, F; Carbajal-González, M T; Fregeneda-Grandes, J M; Aller-Gancedo, J M; Rojo-Vázquez, F A

    2010-02-15

    In this work the clinical evolution and the specific serum IgG and IgE antibody responses in sheep after primary (n=10) and secondary (n=4) experimental challenges with the mange mite Sarcoptes scabiei var. ovis were studied. The primary infection was characterized by the development of mange lesions in all sheep, a detection of live S. scabiei mites in 70% skin scrapings taken in week 10 post-challenge (PC), strongly raised and sustained specific IgG levels and a more moderate but continuous rise in specific IgE levels. Seroconversion was detected for IgG and IgE by ELISA in 90% and 60% of the sheep in week 8 PC, respectively. By Western-blotting (WB), ten IgG-reactive bands (36-120 kDa) and four IgE-reactive bands (90-180 kDa) were observed in week 8 PC. Following the secondary challenge the ewes developed a smaller area of mange lesion than that seen following primary challenge and live S. scabiei mites were not detected in skin scrapings collected in week 8 PC, suggesting that sheep had developed immunity to re-infection. Compared to primary infection, the specific IgG secondary antibody levels were transient, but in contrast there was an anamnestic IgE response, resulting in an elicitation of specific serum IgE levels in week 2 PC significantly higher than those demonstrated after primary infection. WB analysis revealed one additional IgG-reactive band (180 kDa) and no additional IgE-reactive bands. Determining the immunodiagnostic or vaccination value of the IgG-reactive antigens and IgE-reactive allergens detected requires further studies. Copyright 2009 Elsevier B.V. All rights reserved.

  3. Protective effects of chicken egg yolk antibody (IgY) against experimental Vibrio splendidus infection in the sea cucumber (Apostichopus japonicus).

    Science.gov (United States)

    Li, Xiaoyu; Jing, Kailin; Wang, Xitao; Li, Yuan; Zhang, Meixia; Li, Zhen; Xu, Le; Wang, Lili; Xu, Yongping

    2016-01-01

    Vibrio splendidus is one of the most harmful pathogens associated with skin ulceration syndrome in the sea cucumber (Apostichopus japonicus) due to its high virulence and frequency of appearance. The objective of this study was to determine the effectiveness of chicken egg yolk antibody (IgY) against V. splendidus infection in the sea cucumber. Whole V. splendidus cells were used as an immunogen to immunize 20 White Leghorn hens (25 weeks old). IgY was produced from egg yolks obtained from these immunized hens using water dilution, two-step salt precipitation and ultrafiltration. The purity of the IgY produced was approximately 83%. Enzyme-linked Immunosorbent Assay indicated a high specificity for IgY with a maximum antibody titer of 320,000. The growth of V. splendidus in liquid medium was significantly inhibited by IgY in a dose-dependent manner at concentrations ranging from 1 to 10 mg/mL. The protective effects of IgY were evaluated in sea cucumber by intraperitoneally injecting anti-V. splendidus IgY antibodies (10 mg/mL) or immersing the sea cucumber in aqueous IgY (1 g/L) after an intraperitoneal injection of V. splendidus. Intraperitoneal injection resulted in an 80% survival while immersion resulted in a 75% survival during the 11-day experimental period. The survival rates were significantly higher than the positive control and the non-specific IgY group (P < 0.05). As well, the bacterial burden in the respiratory tree, intestine and coelomic liquid was significantly (P < 0.05) lower in sea cucumber treated with specific IgY than those treated with non-specific IgY. The phagocytosis of coelomocytes for V. splendidus in the presence of specific IgY was significantly (P < 0.05) higher than that obtained with non-specific IgY or without IgY, suggesting that specific IgY enhanced phagocytic activity. The current work suggests that specific IgY has potential for protecting sea cucumbers against V. splendidus infection. Copyright © 2015

  4. scFv from Antibody That Mimics gp43 Modulates the Cellular and Humoral Immune Responses during Experimental Paracoccidioidomycosis.

    Science.gov (United States)

    Jannuzzi, Grasielle Pereira; Tavares, Aldo Henrique F P; Kaihami, Gilberto Hideo; de Almeida, José Roberto Fogaça; de Almeida, Sandro Rogério; Ferreira, Karen Spadari

    2015-01-01

    Paracoccidioidomycosis (PCM), caused by Paracoccidioides species is a prevalent systemic and progressive mycosis that occurs in Latin America. It is caused by Paracoccidioides species. Immunization with dendritic cells transfected with a plasmid encoding the scFv (pMAC/PS-scFv) that mimics the main antigen of P. brasiliensis (gp43) confers protection in experimental PCM. DCs link innate and adaptive immunity by recognizing invading pathogens and selecting the type of effector T cell to mediate the immune response. Here, we showed that DC-pMAC/PS-scFv induces the activation of CD4+ and CD8+ T cells. Moreover, our results demonstrated that BALB/c mice infected with P. brasiliensis and treated with DC-pMAC/PS-scFv showed the induction of specific IgG production against gp43 and IFN-γ, IL-12 and IL-4 cytokines. Analysis of regional lymph nodes revealed increases in the expression of clec7a, myd88, tlr2, gata3 and tbx21, which are involved in the immune response. Taken together, our results indicate that the scFv modulates the humoral and cellular immune responses and presents epitopes to CD4+ and CD8+ T cells.

  5. Relation of immediate and delayed thallium-201 distribution to localization of iodine-125 antimyosin antibody in acute experimental myocardial infarction

    International Nuclear Information System (INIS)

    Khaw, B.A.; Strauss, H.W.; Pohost, G.M.; Fallon, J.T.; Katus, H.A.; Haber, E.

    1983-01-01

    Thallium-201 (TI-201) distribution in acute experimental myocardial infarction (MI) (n . 18) was compared with cardiac-specific antimyosin Fab (AM-Fab) uptake, a specific marker for myocardial necrosis. When antimyosin was injected 4 hours after ligation with TI-201 administered 23 hours 55 minutes later and measurement of myocardial distribution determined 5 minutes after intravenous administration of TI-201, (1) TI-201 distribution closely correlated with microsphere regional blood flow, and (2) an inverse exponential relation to iodine-125 (I-125) AM-Fab uptake was apparent. In another group of 4 animals, TI-201 and AM-Fab were administered intravenously 4 hours after MI, and 36 hours later myocardial distribution was measured. This delayed TI-201 distribution had a close inverse linear correlation with I-125 AM-Fab uptake. This inverse linear relation also was apparent in 28-hour-old MIs in dogs (n . 4) where collateral circulation had been established. TI-201 was administered intravenously at 27 hours after MI, and TI-201 distribution was determined 1 hour later. The present study demonstrated that whereas immediate TI-201 distribution is flow-limited, delayed TI-201 distribution is a marker of cell viability which, due to prolonged circulation time and redistribution, is not flow-limited

  6. Chronic experimental autoimmune encephalomyelitis in the guinea pig. Presence of anti-M2 antibodies in central nervous system tissue and the possible role of M2 autoantigen in the induction of the disease.

    Science.gov (United States)

    Lebar, R; Baudrimont, M; Vincent, C

    1989-04-01

    Experimental autoimmune encephalomyelitis (EAE) can be transferred adoptively with T cells sensitized to the basic protein of myelin (BP). However, in the guinea pig, the chronic form of EAE has not been found to be inducible with BP alone, nor has it been adoptively transferred. An antibody response to the central nervous system (CNS) myelin autoantigens was looked for in serum and target CNS tissue in S13 guinea pigs with isologous CNS tissue-induced chronic EAE. Antibody activity was estimated by an immunoenzymatic technique and by autoradiography, using immunoprecipitated and electrophoresed relevant radiolabelled antigens. In serum, IgG antibody response to BP and M2 reached its maximum level 30 to 40 d after immunization and then declined progressively until it became undetectable. On the other hand, while anti-BP antibodies were seldom detected in CNS tissue acid extract, anti-M2 IgG antibodies were always present in CNS tissue of chronic EAE animals, and the amount of these antibodies were related to the severity of symptoms and lesions. No antibody response to proteolipid or to galactocerebroside was detected in serum or CNS tissue. BP-immunized controls showed no chronic EAE and no response to M2 in their serum or CNS tissue. Inasmuch as M2 has been shown to be a glycoprotein of CNS myelin, and anti-M2 antibodies to have a demyelinating property, the latter would be responsible for CNS tissue demyelination in chronic EAE. A shared role of BP and M2 in the induction of chronic EAE in the guinea pig is suggested.

  7. 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

  8. Promise Zones for Applicants

    Data.gov (United States)

    Department of Housing and Urban Development — This tool assists applicants to HUD's Promise Zone initiative prepare data to submit with their application by allowing applicants to draw the exact location of the...

  9. Multiple antigen target approach using the Accuplex4 BioCD system to detect Borrelia burgdorferi antibodies in experimentally infected and vaccinated dogs.

    Science.gov (United States)

    Moroff, Scott; Woodruff, Colby; Woodring, Todd; Sokolchik, Irene; Lappin, Michael R

    2015-09-01

    The primary objective of our study was to optimize detection of serum antibodies to Borrelia burgdorferi using a new commercial automated fluorescence system (Accuplex4 BioCD system, Antech Diagnostics, Lake Success, New York). The system used multiple natural and artificial peptides-outer surface proteins (OspA, OspC, OspF), an outer membrane protein (P39), and a proprietary synthetic peptide (small Lyme peptide [SLP])-and the results were compared with a commercially available enzyme-linked immunosorbent assay that uses a proprietary peptide (C6). Sera from 4 groups were evaluated: dogs vaccinated with 1 of 3 commercially available vaccines (n = 18); dogs infested with adult Ixodes scapularis (black-legged tick; n = 18); dogs previously vaccinated and then infested with I. scapularis (n = 18); and dogs with B. burgdorferi infection that were then vaccinated (n = 14). All of the vaccines evaluated induced OspA responses. However, antibodies against OspF or C6 were not induced in any of the vaccinated dogs. Additionally, the OspF antibodies had 100% sensitivity and specificity when compared to antibodies against C6 peptide. In B. burgdorferi-infected dogs, antibodies against OspC and SLP were detected in serum sooner than antibodies against the other targets. Low levels of antibodies against OspA developed in 6 of 14 B. burgdorferi-infected, unvaccinated dogs and had the shortest duration compared to the other antibodies. Detection of antibody responses to multiple B. burgdorferi targets with this system can be used to help differentiate vaccinated dogs from exposed dogs as well as acute infection from chronic infection. © 2015 The Author(s).

  10. Radioimmunotherapy with an antibody to HPV16 E6 oncoprotein is effective in experimental cervical tumor expressing low levels of E6

    Science.gov (United States)

    Jiang, Zewei; Wang, Xing Guo; Einstein, Mark H; Goldberg, Gary L; Casadevall, Arturo

    2010-01-01

    Purpose HPV16 is associated with ∼50% of all cervical cancers worldwide. The E6 and E7 genes of oncogenic HPV types, such as HPV16, are necessary for the HPV transforming function and tumorogenesis making them ideal targets for novel treatments. Radioimmunotherapy employs systemically administered radiolabeled monoclonal antibodies (mAbs) that bind to tumor-associated antigens. Previously we demonstrated in mice that radioimmunotherapy targeting viral antigens with mAb to HPV16 E6 suppressed CasKi cervical tumors expressing high levels of E6 (∼600 copies of HPV per cell). However, that study opened the question whether radioimmunotherapy can suppress the growth of cervical tumors with low E6 and E7 expression, such as may be seen in patients. Experimental Design We evaluated the expression of E6 in patients' tumors and in the SiHa cell line expressing low levels of E6 and E7 (1–2 copies of HPV per cell) and found them comparable. We initiated SiHa tumors in nude mice, radiolabeled C1P5 mAb to E6 with a beta-emitter 188-Rhenium (188Re) and treated tumor-bearing mice with: (1) 200 µCi 188Re-C1P5 alone; (2) proteasome inhibitor MG132 alone; (3) MG132 followed by 200 µCi 188Re-C1P5; (4) unlabeled C1P5; (5) 200 µCi 188Re-18B7 (isotype-matching control mAb); (6) no treatment. 188Re-C1P5 alone and in combination with MG-132 significantly retarded tumor growth compared to all control groups. Conclusions Our data demonstrate the possibility to suppress tumor growth by targeting viral antigens even in cervical tumors with low E6 expression and provide additional evidence for the potential usefulness of radioimmunotherapy targeting HPV-related antigens in the clinic. PMID:20861673

  11. {sup 99m}Tc-annexin V and {sup 111}In-antimyosin antibody uptake in experimental myocardial infarction in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sarda-Mantel, Laure; Rouzet, Francois; Martet, Genevieve; Raguin, Olivier; Vrigneaud, Jean-Marc; Guludec, Dominique Le [Bichat Hospital AP-HP, EA 3512, Nuclear Medicine Department, Paris (France); Michel, Jean-Baptiste; Louedec, Liliane [INSERM U460, UFR Bichat, Paris (France); Vanderheyden, Jean-Luc [Theseus Imaging Corporation, Boston, MA (United States); Hervatin, Florence [Bichat Hospital AP-HP, EA 3512, Nuclear Medicine Department, Paris (France); CGA/SHFS, Orsay (France); Khaw, Ban An [Bouve College of Pharmacy and Health Sciences, Center for Drug Targeting and Analysis, Boston, MA (United States)

    2006-03-15

    {sup 99m}Tc-annexin V (ANX) allows scintigraphic detection of apoptotic cells via specific binding to exposed phosphatidylserine. In myocardial infarction, apoptosis of myocytes is variable and depends especially on the presence or absence of coronary reperfusion. In this study, ANX uptake in non-reperfused experimental myocardial infarcts was compared with uptake of a marker of myocyte necrosis ({sup 111}In-antimyosin antibodies, AM) and an immunohistochemical marker of apoptosis (Apostain). The left anterior coronary artery was ligated in 47 Wistar rats, which were then injected with ANX (n=20), AM (n=21) or both (n=6). Myocardial uptake of ANX and AM was determined at 2 h (n=14), 4 h (n=14) and 24 h (n=19) after coronary ligation (CL), by quantitative autoradiography with (n=23) or without (n=24) gamma imaging. Heart-to-lung ratios (HLRs) and infarct-to-remote myocardium activity ratios (INRs) were calculated on the scintigrams and autoradiograms respectively. Cardiac sections were stained with haematoxylin-eosin and Apostain. The above studies were repeated in 12 normal rats. All rats with CL showed increased ANX and AM uptake in cardiac areas on scintigrams 24 h after CL, with HLRs higher than in controls: 3.1{+-}0.6 versus 1.5{+-}0.3 (p=0.001) for ANX and 1.99{+-}0.44 versus 1.01{+-}0.05 (p<0.0005) for AM. Autoradiography showed intense ANX and AM uptake in infarcts, with comparable topography and INRs at 2 h, 4 h and 24 h after CL (4.6{+-}0.9 versus 5.0{+-}1.8 at 24 h), while Apostain staining was very low (0.06{+-}0.06% of cells). In this model of persistent CL, we observed increased ANX uptake in injured myocardium, comparable in intensity, topography and kinetics to that of AM. There was only minimal Apostain staining in the same areas. (orig.)

  12. Preliminary application of radioimmunoscintigraphy with 99Tcm labelled anti-fibrin monoclonal antibody (SZ-63) in experimental steroid-induced osteonecrosis in rabbits

    International Nuclear Information System (INIS)

    Zhang Wei; Huang Lixin; Dong Tianhua; Yuan Changgeng

    2002-01-01

    Objective: To evaluate the feasibility of radioimmunoscintigraphy of steroid-induced osteonecrosis with 99 Tc m labelled monoclonal antibody against human fibrin (SZ-63) and to explore the mechanisms postulated in the pathogenesis of steroid-induced osteonecrosis. Methods: Experimental steroid-induced osteonecrosis was produced by intravenous horse serum combined with intraperitoneal high-dose of dexamethasone in 14 healthy adult rabbits, and then radioimmunoscintigraphy with 99 Tc m -SZ-63 was performed. The acquired images were analyzed in comparison with histopathological findings. The other 5 healthy adult rabbits received injection of normal saline instead of horse serum or steroids were used as control. Results: The histopathological observation showed that 10 of 14 model rabbits (71.43%) had osteonecrosis in the femoral head (osteonecrosis group) and no osteonecrosis signs were found in the remaining 4 model rabbits (28.57%, non-osteonecrosis group) and either in the control group. In the osteonecrosis group, the radioactivity uptake increased markedly in both ends of the femur, especially in the femoral head 4 h after injection of 99 Tc m -SZ-63. No abnormal signs were observed in both the non-osteonecrosis group and the control group. The radioactivity ratios of femoral head to trunk were 2.16 +- 0.35, 1.68 +- 0.29 and 1.57 +- 0.12 in osteonecrosis group, non-osteonecrosis group and control group, respectively. There was statistical difference between the former two groups (P 0.05). Conclusions: Steroid-induced osteonecrosis is correlative to thrombosis. Radioimmunoscintigraphy with 99 Tc m -SZ-63 could specifically detect in vivo thrombosis of the steroid-induced osteonecrosis in the rabbit models, and it may provide a great potential of early noninvasive diagnosis of osteonecrosis and screening high-risk group of steroid-induced osteonecrosis

  13. 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

  14. Radiolabeling and animal experimental studies of anti-breast cancer McAb 6C6 and mouse-human chimeric antibody 6C6CHI

    International Nuclear Information System (INIS)

    Yang Zhi; Hu Xiaoqian; Li Erqiu

    2003-01-01

    The aim of this work is to study bio-distribution and tumor absorption of anti breast cancer monoclonal antibody 6C6 and its chimeric antibody 6C6-CHI. The modified Schwartz method was employed to label 6C6 and 6C6CHI with 99 Tc m . The labeled antibody was injected to mouse via tail vein and the blood clearance and whole body clearance were observed. Nude mice bearing breast cancer MCF7 were injected with 99 Tc m -labeled antibody and the bio-distribution was studied and imaged with γ-ray camera. The yield of the two labeled antibodies was more than 90% and their immunoactivities were more than 80%. The whole body eliminated half-time of 99 Tc m -6C6 was 4.1h, and the half-times in blood were T α =0.55h and T β =12.42h respectively. The whole body half-time of 99 Tc m -6C6CHI was 4.28h and the half-times in blood were T α =0.98h and T β =12.42h respectively. The bio-distribution of nude mice bearing breast cancer MCF7 cells was as follows: the ID%/g of tumor and blood was (7.42±0.85) and (5.67±1.44) respectively at 23h after injection of 99 Tc m -6C6. The T/NT (tumor to non tumor) ratios were all more than 1.0 except kidney and the ID%/g of tumor and blood was (4.23±0.64) and (6.97±0.23) respectively at 23 h after injection of 99 Tc m -6C6CHI. The T/NT (tumor to non tumor) ratios were all more than 1.0 except blood and kidney. The γ imaging results showed that the tumor was imaged clearly at 24h after injection of radiolabeled antibodies and the other organs did not concentrate the antibodies except kidney. Anti-breast cancer monoclonal antibody 6C6 can be well located in tumor. Although ID%/g of tumor of the chimeric antibody 6C6CHI was slightly lower than that of 6C6 antibody, and ID%/g of blood was higher than that of 6C6, the tumor imaging of 6C6-CHI was also clear

  15. Biodistribution and pharmacokinetics of monoclonal antibody T1h and variant anti-CD6 murine 10D12 in healthy animals and in experimental arthritis model

    International Nuclear Information System (INIS)

    León, M; Hernández, I; Aldana, L; Ayra, F; Castro, Y; Leyva, R; García, L; Pérez, S.; Casaco, A.

    2016-01-01

    Biodistribution and pharmacokinetic of two radio labeled monoclonal antibodies was performed with the help of imaging techniques. Isotopic labeling was carried out by means of standardized methods. Pharmacokinetic evaluation was performed using the population approach and sparse data design. Introduction: Targeted therapy with monoclonal antibodies (MAb) is an efficient option for the treatment of rheumatoid arthritis. Th1 is a MAb anti human CD6 developed for the treatment of autoimmune disease and 10D12 is its counterpart anti murine CD6 developed as a pharmacological tool to get deep into the response mechanisms in animals models of rheumatoid arthritis.To investigate the behavior of both antibodies in the assay system, molecules were labeled with 125I to evaluate pharmacokinetic in healthy animals and with 99mTc to evaluate the antibody uptake in inflamed area of induced arthritis. Materials and methods: Antibodies were supplied by the Center of Molecular immunology. Iodination was performed by the iodogen method and technetium labeling was carried out directly by Schwarz method. Female C57BL6 from CENPALAB were used for experiments. Biodistribution and pharmacokinetic was performed by a sparse data design using the population approach. Uptake in region of inflammation was quantified by gammagraphy at the same time points of blood sampling. A compartmental model was build to quantify uptake kinetic. Pharmacokinetic profiles were analyzed using MONOLIX software version 4.2. Results: Minor pharmacokinetic differences were found between monoclonal antibodies labeled with 125I and 99mTc. As a humanized antibody, T1h shows a faster clearance than 10D12 and a biodistribution pattern reflecting preference for excretion mechanisms. The arthritis accumulation was not consistent with a targeted mediated uptake. On the other hand, radio labeled 10D12 shows an accumulation profile in arthritis with two peaks of maximum concentration representing an initial transit to

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

    Science.gov (United States)

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

    2015-10-15

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

  17. Antibody responses to a novel Plasmodium falciparum merozoite surface protein vaccine correlate with protection against experimental malaria infection in Aotus monkeys.

    Science.gov (United States)

    Cavanagh, David R; Kocken, Clemens H M; White, John H; Cowan, Graeme J M; Samuel, Kay; Dubbeld, Martin A; Voorberg-van der Wel, Annemarie; Thomas, Alan W; McBride, Jana S; Arnot, David E

    2014-01-01

    The Block 2 region of the merozoite surface protein-1 (MSP-1) of Plasmodium falciparum has been identified as a target of protective immunity by a combination of seroepidemiology and parasite population genetics. Immunogenicity studies in small animals and Aotus monkeys were used to determine the efficacy of recombinant antigens derived from this region of MSP-1 as a potential vaccine antigen. Aotus lemurinus griseimembra monkeys were immunized three times with a recombinant antigen derived from the Block 2 region of MSP-1 of the monkey-adapted challenge strain, FVO of Plasmodium falciparum, using an adjuvant suitable for use in humans. Immunofluorescent antibody assays (IFA) against erythrocytes infected with P. falciparum using sera from the immunized monkeys showed that the MSP-1 Block 2 antigen induced significant antibody responses to whole malaria parasites. MSP-1 Block 2 antigen-specific enzyme-linked immunosorbent assays (ELISA) showed no significant differences in antibody titers between immunized animals. Immunized animals were challenged with the virulent P. falciparum FVO isolate and monitored for 21 days. Two out of four immunized animals were able to control their parasitaemia during the follow-up period, whereas two out of two controls developed fulminating parasitemia. Parasite-specific serum antibody titers measured by IFA were four-fold higher in protected animals than in unprotected animals. In addition, peptide-based epitope mapping of serum antibodies from immunized Aotus showed distinct differences in epitope specificities between protected and unprotected animals.

  18. Antibody pretargeting advances cancer radioimmunodetection and radioimmunotherapy.

    Science.gov (United States)

    Goldenberg, David M; Sharkey, Robert M; Paganelli, Giovanni; Barbet, Jacques; Chatal, Jean-François

    2006-02-10

    This article reviews the methods of pretargeting, which involve separating the targeting antibody from the subsequent delivery of an imaging or therapeutic agent that binds to the tumor-localized antibody. This provides enhanced tumor:background ratios and the delivery of a higher therapeutic dose than when antibodies are directly conjugated with radionuclides, as currently practiced in cancer radioimmunotherapy. We describe initial promising clinical results using streptavidin-antibody constructs with biotin-radionuclide conjugates in the treatment of patients with malignant gliomas, and of bispecific antibodies with hapten-radionuclides in the therapy of tumors expressing carcinoembryonic antigen, such as medullary thyroid and small-cell lung cancers.

  19. Experimental and clinical analysis of the characteristics of a chimeric monoclonal antibody, MOv18, reactive with an ovarian cancer-associated antigen

    NARCIS (Netherlands)

    Molthoff, C. F.; Buist, M. R.; Kenemans, P.; Pinedo, H. M.; Boven, E.

    1992-01-01

    Monoclonal antibody (Mab) MOv18 preferentially reacts with gynecological carcinomas. We have analyzed the characteristics of murine MOv18 (m-MOv18) and chimeric MOv18 (c-MOv18). We found no differences in affinity and binding to IGROV1 cells between c-MOv18 as IgG and F(ab')2 fragments and m-MOv18.

  20. Emergence of viruses resistant to neutralization by V3-specific antibodies in experimental human immunodeficiency virus type 1 IIIB infection of chimpanzees

    NARCIS (Netherlands)

    Nara, P. L.; Smit, L.; Dunlop, N.; Hatch, W.; Merges, M.; Waters, D.; Kelliher, J.; Gallo, R. C.; Fischinger, P. J.; Goudsmit, J.

    1990-01-01

    Emergence in two chimpanzees of human immunodeficiency virus type 1 (HIV-1) IIIB variants resistant to neutralization by the preexisting antibody is described. Viruses isolated from the HIV-1 IIIB gp120-vaccinated and -challenged animal were more resistant to neutralization by the chimpanzee's own

  1. Opposites attract in bispecific antibody engineering

    NARCIS (Netherlands)

    van Gils, Marit J.; Sanders, Rogier W.

    2017-01-01

    Bispecific antibodies show great promise as intrinsic combination therapies, but often suffer from poor physiochemical properties, many times related to poor heterodimerization. De Nardis et al. identify specific electrostatic interactions that facilitate efficient heterodimerization, resulting in

  2. The promise of dialogue

    DEFF Research Database (Denmark)

    Phillips, Louise Jane

    traditions - dialogic communication theory, action research, and science and technology studies. It also provides an empirically rich account of the dialogic turn through case studies of how dialogue is enacted in the fields of planned communication, public engagement with science and collaborative research...... in the fields in which it is practised and how can we analyse those practices in ways that take account of their complexities? The Promise of Dialogue presents a novel theoretical framework for analysing the dialogic turn in the production and communication of knowledge that builds bridges across three research...

  3. Promising change, delivering continuity

    DEFF Research Database (Denmark)

    Lund, Jens Friis; Sungusia, Eliezeri; Mabele, Mathew Bukhi

    2017-01-01

    that compares the emergence of REDD+ in Tanzania with that of a previous forest-policy model called Participatory Forest Management. Our study describes how the advent of REDD+ implies change at the discursive level, but also continuity and repetitiveness in terms of the initial promises and expectations...... leading to substantial donor financing, pilot project activities, and policy development and implementation processes. In both epochs, these have achieved little in terms of changing actual forest management and use on the ground outside selected pilot project sites, but have sustained the livelihoods...

  4. Evaluation of a rapid immunochromatographic dipstick test for detection of antibodies to Trypanosoma cruzi in dogs experimentally infected with isolates obtained from opossums (Didelphis virginiana), armadillos (Dasypus novemcinctus), and dogs (Canis familiaris) from the United States.

    Science.gov (United States)

    Rosypal, Alexa C; Hill, Roderick; Lewis, Samantha; Barr, Stephen C; Valadas, Samantha; Gennari, Solange Maria; Lindsay, David S

    2011-02-01

    Dogs are reservoir hosts for Trypanosoma cruzi , the causative agent of American trypanosomiasis. A rapid immunochromatographic dipstick test (ICT) is available commercially for canine serological testing. The ICT was developed with the use of sera from South American dogs, but it is not routinely used in the United States. We evaluated the utility of the ICT in detecting anti-T. cruzi antibodies in dogs from the United States. Dogs (N  =  64) were experimentally infected with United States' isolates of T. cruzi from an opossum (Didelphis virginiana), an armadillo (Dasypus novemcinctus), and a domestic dog (Canis familiaris), and were tested after experimental infection. Sera from uninfected United States dogs (n  =  79; hemaculture negative) were used as negative controls. In a blind study, sera were tested by the ICT and compared to the indirect immunofluorescent antibody test with the use of Brazil-strain epimastigotes as antigen. The sensitivity of the ICT was 91% and the specificity was 98% in dogs experimentally infected with United States isolates. Our study indicates that the ICT could be a useful screening tool for serological surveillance of canine T. cruzi exposure in the United States.

  5. Cancer chemoprevention: progress and promise.

    Science.gov (United States)

    Kelloff, G J; Sigman, C C; Greenwald, P

    1999-12-01

    Cancer chemoprevention is the use of agents to inhibit, delay or reverse carcinogenesis. The focus of chemoprevention research in the next millennium will include defining the genotypic and phenotypic (functional and histological) changes during carcinogenesis, the cancer risk conferred by these changes, their modulation in preclinical experimentation and randomised clinical trials by chemopreventive drugs, dietary agents and regimens and treatments resulting from early detection. The key elements of this research effort will be basic and translational risk evaluation programmes; chemopreventive and dietary agent drug discovery and development; development of transgenic animal models; required safety and pharmacology studies; well-designed phase I, II and III chemoprevention studies; and much expanded early detection programmes. The large number of chemoprevention research programmes now ongoing ensures that the promise of chemoprevention will continue to be realised in the next decade.

  6. Antibody-Directed Phototherapy (ADP

    Directory of Open Access Journals (Sweden)

    M. Adil Butt

    2013-04-01

    Full Text Available Photodynamic therapy (PDT is a clinically-approved but rather under-exploited treatment modality for cancer and pre-cancerous superficial lesions. It utilises a cold laser or LED to activate a photochemical reaction between a light activated drug (photosensitiser-drug and oxygen to generate cytotoxic oxygen species. These free radical species damage cellular components leading to cell death. Despite its benefits, the complexity, limited potency and side effects of PDT have led to poor general usage. However, the research area is very active with an increasing understanding of PDT-related cell biology, photophysics and significant progress in molecular targeting of disease. Monoclonal antibody therapy is maturing and the next wave of antibody therapies includes antibody-drug conjugates (ADCs, which promise to be more potent and curable. These developments could lift antibody-directed phototherapy (ADP to success. ADP promises to increase specificity and potency and improve drug pharmacokinetics, thus delivering better PDT drugs whilst retaining its other benefits. Whole antibody conjugates with first generation ADP-drugs displayed problems with aggregation, poor pharmacokinetics and loss of immuno-reactivity. However, these early ADP-drugs still showed improved selectivity and potency. Improved PS-drug chemistry and a variety of conjugation strategies have led to improved ADP-drugs with retained antibody and PS-drug function. More recently, recombinant antibody fragments have been used to deliver ADP-drugs with superior drug loading, more favourable pharmacokinetics, enhanced potency and target cell selectivity. These improvements offer a promise of better quality PDT drugs.

  7. B cell and antibody responses in mice induced by a putative cell surface peptidase of Pneumocystis murina protect against experimental infection.

    Science.gov (United States)

    Ruan, Sanbao; Cai, Yang; Ramsay, Alistair J; Welsh, David A; Norris, Karen; Shellito, Judd E

    2017-01-23

    Pneumocystis pneumonia is a major cause of morbidity and mortality in HIV-infected subjects, cancer patients undergoing chemotherapy and solid organ transplant recipients. No vaccine is currently available. By chemical labeling coupled with proteomic approach, we have identified a putative surface protein (SPD1, Broad Institute gene accession number PNEG_01848) derived from single suspended P. murina cysts. SPD1 was expressed in an insect cell line and tested for vaccine development. Mice were immunized with SPD1 plus adjuvant MF-59 by subcutaneous injection. Three weeks after the last immunization, CD4+ cells were depleted with anti-CD4 antibody GK1.5. The mice were then challenged with 2×10 5 Pneumocystis organisms. Mice were sacrificed at 4 and 6weeks after PC challenge. Spleen/lung cells and serum were harvested. B cells and memory B cells were assessed via flow cytometry. Specific Pneumocystis IgG antibody was measured by ELISA before and after challenge. Infection burden was measured as real-time PCR for P. murina rRNA. Normal mice infected with Pneumocystis mounted a serum IgG antibody response to SPD1. Serum from rhesus macaques exposed to Pneumocystis showed a similar serum IgG response to purified SPD1. SPD1 immunization increased B cell and memory B cell absolute cell counts in CD4-depleted Balb/c mice post Pneumocystis challenge in spleen and lung. Immunization with SPD1 significantly increased specific Pneumocystis IgG antibody production before and after challenge. Mice immunized with SPD1 showed significantly decreased P. murina copy number compared with mice that did not receive SPD1 at 6weeks after challenge. Immunization with SPD1 provides protective efficacy against P. murina infection. SPD1 protection against Pneumocystis challenge is associated with enhanced memory B cell production and higher anti-Pneumocystis IgG antibody production. SPD1 is a potential vaccine candidate to prevent or treat pulmonary infection with Pneumocystis. Copyright

  8. Antibody biotechnology

    African Journals Online (AJOL)

    STORAGESEVER

    2009-07-06

    Jul 6, 2009 ... and automated, the hybrid cells can be stored for many years in liquid nitrogen and antibodies production is homogeneous. The hybridoma method .... they may be modified to vehicle active molecules such as radio-isotopes, toxins, cytokines, enzyme etc. In these cases, the therapeutic effect is due to ...

  9. Catalytic Antibodies

    Indian Academy of Sciences (India)

    The ability of the highly evolved machinery of immune system to produce structurally and functionally complex ... to Pauling, if the structure of the antigen binding site of antibodies were to be produced in a random ..... where the immune system of the body is destructive, as in autoimmune disorders or after organ transplant.

  10. Catalytic Antibodies

    Indian Academy of Sciences (India)

    While chemistry provides the framework for understanding the structure and function of biomolecules, the immune sys- tem provides a highly evolved natural process to generate one class of complex biomolecules – the antibodies. A combination of the two could be exploited to generate new classes of molecules with novel ...

  11. Elaboration and quality control of the inoculum of the experimental vaccine Brucella S19-tn7-GFP for use in white animals and associated serological test for the detection of anti-GFP antibodies

    International Nuclear Information System (INIS)

    Salas Alfaro, Dariana

    2014-01-01

    The preparation of the inoculum of the experimental vaccine Brucella S19-Tn7-GFP is optimized for application in white animals. An associated serological test has allowed differentiating infected animals from those vaccinated with the experimental strain. The same bacteriological and biological properties of the B. abortus S19-Tn7-GFP strain have maintained in the parental vaccine strain S19 and is stable over time. A protocol for the inoculums of strain S19-Tn7-GFP is established for its preparation and use in white animals and quality control. The inoculum stability is evaluated through the simulation of conditions that can be presented in the transportation and application process in the field. An enzyme immunoassay ELISA is optimized for the detection of anti-GFP antibodies in cattle [es

  12. Decision Taking versus Promise Issuing

    NARCIS (Netherlands)

    Bergstra, J.A.

    2013-01-01

    An alignment is developed between the terminology of outcome oriented decision taking and a terminology for promise issuing. Differences and correspondences are investigated between the concepts of decision and promise. For decision taking, two forms are distinguished: the external outcome

  13. The Promises of Biology and the Biology of Promises

    DEFF Research Database (Denmark)

    Lee, Jieun

    2015-01-01

    commitments with differently imagined futures. I argue that promises are constitutive of the stem cell biology, rather than being derivative of it. Since the biological concept of stem cells is predicated on the future that they promise, the biological life of stem cells is inextricably intertwined...... patients’ bodies in anticipation of materializing the promises of stem cell biology, they are produced as a new form of biovaluable. The promises of biology move beyond the closed circuit of scientific knowledge production, and proliferate in the speculative marketplaces of promises. Part II looks at how...... of technologized biology and biological time can appear promising with the backdrop of the imagined intransigence of social, political, and economic order in the Korean society....

  14. Promising treatments of tomorrow for multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Harrison Daniel

    2009-01-01

    Full Text Available The therapeutic options for multiple sclerosis are rapidly expanding. What was once seen as a disease with little hope for treatment is now a target of rapid drug development. Current therapies have demonstrated efficacy in limiting the impact of the disease, but none is fully effective in all patients. However, promising new treatments are on the horizon. In this review we will discuss potential novel immunomodulating drugs that are in advanced stages of investigation; these drugs include monoclonal antibodies, chimeric molecules, and oral therapies. The use of hematopoietic stem cells will also be discussed and, in addition, we will look farther ahead at possible novel targets for the development of new immunomodulatory or neuroprotective pharmaceuticals.

  15. An Anti-Urokinase Plasminogen Activator Receptor Antibody (ATN-658 Blocks Prostate Cancer Invasion, Migration, Growth, and Experimental Skeletal Metastasis In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Shafaat A. Rabbani

    2010-10-01

    Full Text Available Urokinase plasminogen activator receptor (uPAR is a multidomain protein that plays important roles in the growth, invasion, and metastasis of a number of cancers. In the present study, we examined the effects of administration of a monoclonal anti-uPAR antibody (ATN-658 on prostate cancer progression in vitro and in vivo. We examined the effect of treatment of ATN-658 on human prostate cancer cell invasion, migration, proliferation, and regulation of intracellular signaling pathways. For in vivo studies, PC-3 cells (1 x 106 were inoculated into the right flank of male Balb C nu/nu mice through subcutaneous or through intratibial route (2 x 105 of male Fox Chase severe combined immunodeficient mice to monitor the effect on tumor growth and skeletal metastasis. Treatment with ATN-658 resulted in a significant dose-dependent decrease in PC-3 cell invasion and migration without affecting cell doubling time. Western blot analysis showed that ATN-658 treatment decreased the phosphorylation of serine/threonine protein kinase B (AKT, mitogen-activated protein kinase (MAPK, and focal adhesion kinase (FAK without affecting AKT, MAPK, and FAK total protein expression. In in vivo studies, ATN-658 caused a significant decrease in tumor volume and a marked reduction in skeletal lesions as determined by Faxitron x-ray and micro-computed tomography. Immunohistochemical analysis of subcutaneous and tibial tumors showed a marked decrease in the levels of expression of pAKT, pMAPK, and pFAK, consistent with the in vitro observations. Results from these studies provide compelling evidence for the continued development of ATN-658 as a potential therapeutic agent for the treatment of prostate and other cancers expressing uPAR.

  16. Clinical efficacy and management of monoclonal antibodies targeting CD38 and SLAMF7 in multiple myeloma

    DEFF Research Database (Denmark)

    van de Donk, Niels W C J; Moreau, Philippe; Plesner, Torben

    2016-01-01

    Immunotherapeutic strategies are emerging as promising therapeutic approaches in multiple myeloma (MM), with several monoclonal antibodies in advanced stages of clinical development. Of these agents, CD38-targeting antibodies have marked single agent activity in extensively pretreated MM, and pre...

  17. The antibody Hijikata Tatsumi

    Directory of Open Access Journals (Sweden)

    Éden Peretta

    2012-11-01

    Full Text Available Considered one of the most influential modern dance representatives in Japan, Tatsumi Hijikata’s work was a milestone in the Japanese post-war experimental artistic scene. Heretic son of his time, he staged a fertile mix of artistic and cultural influences, overlapping subversive elements of European arts and philosophy with radical references from pre-modern Japanese culture. In this way he built the foundations of its unstable antibody, its political-artistic project of dissolution of a organism, both physical and social.

  18. Prevalence of antibodies against Kilham virus in experimental rat colonies of Argentina Prevalencia de anticuerpos contra el virus Kilham en colonias experimentales de ratas de Argentina

    Directory of Open Access Journals (Sweden)

    M. P. Cagliada

    2010-02-01

    Full Text Available The Kilham rat virus (KRV is a parvovirus originally isolated from a rat sarcoma in the late 1950s. The clinical signs associated with a natural KRV infection include foetal resorption in dams, runtin, ataxia, cerebellar hypoplasia and jaundice in suckling rats, and sudden death, scrotal cyanosis, abdominal swelling and dehydration in juvenile rats. The ability of this virus to produce persistent infections has resulted in a high frequency of contamination of cell cultures and transplantable-tumor system. In addition, the virus may interfere with research in other ways. The remarkable resistance to environmental conditions determines the importance of the detection and control of this agent, especially in the laboratory animal production. This study determines the seroprevalence of Kilham antibodies from sera of adult rats from conventional facilities, using the haemagglutination inhibition test. The seroprevalence varied between 27.8% and 75%. This result confirms that the virus is circulating in Argentinean conventional facilities and might be interfering with research. The recognized Kilham virus may be prevented from supply sources by implementing a health monitoring schedule including a regular serological surveillance, and by keeping the animals under barrier systems.El virus Kilham es un parvovirus aislado originalmente a partir de un sarcoma de rata, a fines de la década del 50. Los signos clínicos que produce son reabsorción fetal, disminución del crecimiento, ataxia, hipoplasia cerebelar, ictericia en lactantes, muerte súbita, cianosis escrotal, hinchazón abdominal y deshidratación de ratas jóvenes. La capacidad del virus para producir infecciones persistentes hace que los cultivos celulares derivados de ratas puedan estar contaminados. Además, el virus puede interferir con los ensayos de investigación de diferentes formas. La resistencia a las condiciones ambientales determina la importancia de la detección y el control de

  19. Antibodies: an alternative for antibiotics?

    Science.gov (United States)

    Berghman, L R; Abi-Ghanem, D; Waghela, S D; Ricke, S C

    2005-04-01

    In 1967, the success of vaccination programs, combined with the seemingly unstoppable triumph of antibiotics, prompted the US Surgeon General to declare that "it was time to close the books on infectious diseases." We now know that the prediction was overly optimistic and that the fight against infectious diseases is here to stay. During the last 20 yr, infectious diseases have indeed made a staggering comeback for a variety of reasons, including resistance against existing antibiotics. As a consequence, several alternatives to antibiotics are currently being considered or reconsidered. Passive immunization (i.e., the administration of more or less pathogen-specific antibodies to the patient) prior to or after exposure to the disease-causing agent is one of those alternative strategies that was almost entirely abandoned with the introduction of chemical antibiotics but that is now gaining interest again. This review will discuss the early successes and limitations of passive immunization, formerly referred to as "serum therapy," the current use of antibody administration for prophylaxis or treatment of infectious diseases in agriculture, and, finally, recent developments in the field of antibody engineering and "molecular farming" of antibodies in various expression systems. Especially the potential of producing therapeutic antibodies in crops that are routine dietary components of farm animals, such as corn and soy beans, seems to hold promise for future application in the fight against infectious diseases.

  20. 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.

  1. Peptide-Based Vaccinology: Experimental and Computational Approaches to Target Hypervariable Viruses through the Fine Characterization of Protective Epitopes Recognized by Monoclonal Antibodies and the Identification of T-Cell-Activating Peptides

    Directory of Open Access Journals (Sweden)

    Matteo Castelli

    2013-01-01

    Full Text Available Defining immunogenic domains of viral proteins capable of eliciting a protective immune response is crucial in the development of novel epitope-based prophylactic strategies. This is particularly important for the selective targeting of conserved regions shared among hypervariable viruses. Studying postinfection and postimmunization sera, as well as cloning and characterization of monoclonal antibodies (mAbs, still represents the best approach to identify protective epitopes. In particular, a protective mAb directed against conserved regions can play a key role in immunogen design and in human therapy as well. Experimental approaches aiming to characterize protective mAb epitopes or to identify T-cell-activating peptides are often burdened by technical limitations and can require long time to be correctly addressed. Thus, in the last decade many epitope predictive algorithms have been developed. These algorithms are continually evolving, and their use to address the empirical research is widely increasing. Here, we review several strategies based on experimental techniques alone or addressed by in silico analysis that are frequently used to predict immunogens to be included in novel epitope-based vaccine approaches. We will list the main strategies aiming to design a new vaccine preparation conferring the protection of a neutralizing mAb combined with an effective cell-mediated response.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. Persistence of specific antibody response in different experimental infections of mice with Toxocara canis larvae Persistência da resposta humoral em camundongos experimentalmente infectados com larvas de Toxocara canis

    Directory of Open Access Journals (Sweden)

    Pedro Paulo Chieffi

    1995-06-01

    Full Text Available Anti-Toxocara antibody production and persistence were studied in experimental infections of BALB/c mice, according to three different schedules: Group I (GI - 25 mice infected with 200 T. canis eggs in a single dose; Group II (GII 25 mice infected with 150 T. canis eggs given in three occasions, 50 in the 1st, 50 in the 5th and 50 in the 8th days; Group III (GIII - 25 mice also infected with 150 T. canis eggs, in three 50 eggs portions given in the 1st, 14th and 28th days. A 15 mice control group (GIV was maintained without infection. In the 30th, 50th, 60th, 75th, 105th and 180th post-infection days three mice of the GI, GII and GIII groups and two mice of the control group had been sacrificed and exsanguinated for sera obtention. In the 360th day the remainder mice of the four groups were, in the same way, killed and processed. The obtained sera were searched for the presence of anti-Toxocara antibodies by an ELISA technique, using T. canis larvae excretion-secretion antigen. In the GI and GII, but not in the GIII, anti-Toxocara antibodies had been found, at least, up to the 180th post-infection day. The GIII only showed anti-Toxocara antibodies, at significant level, in the 30th post-infection day.Estudou-se a cinética de anticorpos anti-Toxocara em camundongos BALB/c infectados experimentalmente segundo três esquemas: Grupo I (GI: 25 camundongos infectados com dose única de 200 ovos embrionados de T. canis; grupo II (GII: 25 camundongos infectados com 150 ovos embrionados de T. canis, divididos em três doses de 50 ovos, administrados no 1º, 5º e 8º dias; Grupo III (GIII: 25 camundongos infectados com 150 ovos embrionados de T. canis, administrados em três doses de 50 ovos no 1º, 14º e 28º dias. Um grupo de 15 camundongos foi mantido nas mesmas condições, porém sem infecção, constituindo o grupo controle (GIV. No 30º, 50º, 60º, 75º, 105º e 180º dias pós-infecção três camundongos dos grupos GI, GII e GIII e dois do

  8. Radiolabeled antibodies for cancer imaging and therapy.

    Science.gov (United States)

    Barbet, Jacques; Bardiès, Manuel; Bourgeois, Mickael; Chatal, Jean-François; Chérel, Michel; Davodeau, François; Faivre-Chauvet, Alain; Gestin, Jean-François; Kraeber-Bodéré, Françoise

    2012-01-01

    Radiolabeled antibodies were studied first for tumor detection by single-photon imaging, but FDG PET stopped these developments. In the meantime, radiolabeled antibodies were shown to be effective in the treatment of lymphoma. Radiolabeling techniques are well established and radiolabeled antibodies are a clinical and commercial reality that deserves further studies to advance their application in earlier phase of the diseases and to test combination and adjuvant therapies including radiolabeled antibodies in hematological diseases. In solid tumors, more resistant to radiations and less accessible to large molecules such as antibodies, clinical efficacy remains limited. However, radiolabeled antibodies used in minimal or small-size metastatic disease have shown promising clinical efficacy. In the adjuvant setting, ongoing clinical trials show impressive increase in survival in otherwise unmanageable tumors. New technologies are being developed over the years: recombinant antibodies and pretargeting approaches have shown potential in increasing the therapeutic index of radiolabeled antibodies. In several cases, clinical trials have confirmed preclinical studies. Finally, new radionuclides, such as lutetium-177, with better physical properties will further improve the safety of radioimmunotherapy. Alpha particle and Auger electron emitters offer the theoretical possibility to kill isolated tumor cells and microscopic clusters of tumor cells, opening the perspective of killing the last tumor cell, which is the ultimate challenge in cancer therapy. Preliminary preclinical and preliminary clinical results confirm the feasibility of this approach.

  9. Antibodies against the majority subunit of type IV Pili disperse nontypeable Haemophilus influenzae biofilms in a LuxS-dependent manner and confer therapeutic resolution of experimental otitis media.

    Science.gov (United States)

    Novotny, Laura A; Jurcisek, Joseph A; Ward, Michael O; Jordan, Zachary B; Goodman, Steven D; Bakaletz, Lauren O

    2015-04-01

    Despite resulting in a similar overall outcome, unlike antibodies directed against the DNABII protein, integration host factor (IHF), which induce catastrophic structural collapse of biofilms formed by nontypeable Haemophilus influenzae (NTHI), those directed against a recombinant soluble form of PilA [the majority subunit of Type IV pili (Tfp) produced by NTHI], mediated gradual 'top-down' dispersal of NTHI from biofilms. This dispersal occurred via a mechanism that was dependent upon expression of both PilA (and by inference, Tfp) and production of AI-2 quorum signaling molecules by LuxS. The addition of rsPilA to a biofilm-targeted therapeutic vaccine formulation comprised of IHF plus the powerful adjuvant dmLT and delivered via a noninvasive transcutaneous immunization route induced an immune response that targeted two important determinants essential for biofilm formation by NTHI. This resulted in significantly earlier eradication of NTHI from both planktonic and adherent populations in the middle ear, disruption of mucosal biofilms already resident within middle ears prior to immunization and rapid resolution of signs of disease in an animal model of experimental otitis media. These data support continued development of this novel combinatorial immunization approach for resolution and/or prevention of multiple diseases of the respiratory tract caused by NTHI. © 2015 John Wiley & Sons Ltd.

  10. Failure of a VapA/CpG oligodeoxynucleotide vaccine to protect foals against experimental Rhocococcus equi pneumonia despite induction of VapA-specific antibody and interferon-γ response.

    Science.gov (United States)

    Lohmann, Katharina L; Lopez, A Marianela; Manning, Stephen T; Marques, Fernando J; Brownlie, Robert; Allen, Andrew L; Sangster, Anna E; Mutwiri, George; Gerdts, Volker; Potter, Andrew; Townsend, Hugh G G

    2013-07-01

    We evaluated the immunogenic and protective potential of a recombinant VapA/CpG oligodeoxynucleotide (ODN) 2395 vaccine in neonatal foals undergoing experimental Rhodococcus equi challenge. Foals (n = 8) were vaccinated by intramuscular injection on days 1 and 15 of the study; control foals (n = 7) received a phosphate-buffered saline (PBS) solution. All foals were challenged by intrabronchial administration of 5 × 10⁶ R. equi 103⁺ on day 29. Bronchoalveolar lavages were done on days 15, 29, and 36 and total cell count, differential cell count, rVapA-stimulated cell proliferation and interferon (IFN)-γ mRNA expression determined. Clinical examination, complete blood (cell) counts, serology for VapA-specific antibodies, and culture of nasal and fecal swabs were done on days 1, 15, 29, 36, 43, and 50. Foals were humanely euthanized on day 50 and severity of pneumonia scored on a 4-point scale. Vaccination resulted in a significant increase in VapA-specific immunoglobulin (Ig) production, with total IgG and IgG(T) being increased by day 15. Expression of VapA-specific IFN-γ mRNA by BAL cells was increased in the vaccinated foals following challenge. Postmortem lung severity scores did not differ between groups. Two foals shed virulent R. equi in feces; however, real-time polymerase chain reaction (PCR) revealed the isolates to be different from the challenge strain.

  11. Mastering JavaScript promises

    CERN Document Server

    Hussain, Muzzamil

    2015-01-01

    This book is for all the software and web engineers wanting to apply the promises paradigm to their next project and get the best outcome from it. This book also acts as a reference for the engineers who are already using promises in their projects and want to improve their current knowledge to reach the next level. To get the most benefit from this book, you should know basic programming concepts, have a familiarity with JavaScript, and a good understanding of HTML.

  12. America: No Promise Without Agony.

    Science.gov (United States)

    Brown, Robert McAfee

    We may discover signs of promise in the midst of agony if we make some shifts of perspective. (1) "Our fear of overt violence must be countered by our acknowledgement of covert violence." Covert violence is subtle and more destructive than physical violence because it is the "denial of personhood"--the insinuation by an act or by neglect that a…

  13. Promising Electric Aircraft Drive Systems

    Science.gov (United States)

    Dudley, Michael R.

    2010-01-01

    An overview of electric aircraft propulsion technology performance thresholds for key power system components is presented. A weight comparison of electric drive systems with equivalent total delivered energy is made to help identify component performance requirements, and promising research and development opportunities.

  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. Experimental Therapy Shows Promise for Type 1 Diabetes

    Science.gov (United States)

    ... triggers cells to take up sugar from the blood. In type 1 diabetes, the immune system The cells and tissues that ... people to eat or drink to raise their blood sugar levels. However, many people with type 1 diabetes can’t tell when their blood sugar is ...

  16. 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...... such as structure, accessibility and amino acid composition are crucial. Since small peptides tend not to be immunogenic, it may be necessary to conjugate them to carrier proteins in order to enhance immune presentation. Several strategies for conjugation of peptide-carriers applied for immunization exist...

  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. HIV antibodies for treatment of HIV infection

    Science.gov (United States)

    Margolis, David M.; Koup, Richard A.; Ferrari, Guido

    2016-01-01

    Summary 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. Further, 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. PMID:28133794

  19. Freedom: A Promise of Possibility.

    Science.gov (United States)

    Bunkers, Sandra Schmidt

    2015-10-01

    The idea of freedom as a promise of possibility is explored in this column. The core concepts from a research study on considering tomorrow (Bunkers, 1998) coupled with humanbecoming community change processes (Parse, 2003) are used to illuminate this notion. The importance of intentionality in human freedom is discussed from both a human science and a natural science perspective. © The Author(s) 2015.

  20. Acetylcholine receptor antibody

    Science.gov (United States)

    ... this page: //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 ...

  1. 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. ...

  2. Biophysical characterization of antibodies with isothermal titration calorimetry

    Directory of Open Access Journals (Sweden)

    Verna Frasca

    2016-07-01

    Full Text Available Antibodies play a key role in the immune response. Since antibodies bind antigens with high specificity and tight affinity, antibodies are an important reagent in experimental biology, assay development, biomedical research and diagnostics. Monoclonal antibodies are therapeutic drugs and used for vaccine development. Antibody engineering, biophysical characterization, and structural data have provided a deeper understanding of how antibodies function, and how to make better drugs. Isothermal titration calorimetry (ITC is a label-free binding assay, which measures affinity, stoichiometry, and binding thermodynamics for biomolecular interactions. When thermodynamic data are used together with structural and kinetic data from other assays, a complete structure-activity-thermodynamics profile can be constructed. This review article describes ITC, and discusses several applications on how data from ITC provides insights into how antibodies function, guide antibody engineering, and aid design of new therapeutic drugs.

  3. Methods to Design and Synthesize Antibody-Drug Conjugates (ADCs

    Directory of Open Access Journals (Sweden)

    Houzong Yao

    2016-02-01

    Full Text Available Antibody-drug conjugates (ADCs have become a promising targeted therapy strategy that combines the specificity, favorable pharmacokinetics and biodistributions of antibodies with the destructive potential of highly potent drugs. One of the biggest challenges in the development of ADCs is the application of suitable linkers for conjugating drugs to antibodies. Recently, the design and synthesis of linkers are making great progress. In this review, we present the methods that are currently used to synthesize antibody-drug conjugates by using thiols, amines, alcohols, aldehydes and azides.

  4. Chitin fulfilling a biomaterials promise

    CERN Document Server

    Khor, Eugene

    2001-01-01

    The second edition of Chitin underscores the important factors for standardizing chitin processing and characterization. It captures the essential interplay between chitin's assets and limitations as a biomaterial, placing the past promises of chitin in perspective, addressing its present realities and offering insight into what is required to realize chitin's destiny (including its derivative, chitosan) as a biomaterial of the twenty-first century. This book is an ideal guide for both industrialists and researchers with a vested interest in commercializing chitin.An upd

  5. Programmed death-1 & its ligands: promising targets for cancer immunotherapy.

    Science.gov (United States)

    Shrimali, Rajeev K; Janik, John E; Abu-Eid, Rasha; Mkrtichyan, Mikayel; Khleif, Samir N

    2015-01-01

    Novel strategies for cancer treatment involving blockade of immune inhibitors have shown significant progress toward understanding the molecular mechanism of tumor immune evasion. The preclinical findings and clinical responses associated with programmed death-1 (PD-1) and PD-ligand pathway blockade seem promising, making these targets highly sought for cancer immunotherapy. In fact, the anti-PD-1 antibodies, pembrolizumab and nivolumab, were recently approved by the US FDA for the treatment of unresectable and metastatic melanoma resistant to anticytotoxic T-lymphocyte antigen-4 antibody (ipilimumab) and BRAF inhibitor. Here, we discuss strategies of combining PD-1/PD-ligand interaction inhibitors with other immune checkpoint modulators and standard-of-care therapy to break immune tolerance and induce a potent antitumor activity, which is currently a research area of key scientific pursuit.

  6. Site-specific proteolytic degradation of IgG monoclonal antibodies expressed in tobacco plants.

    Science.gov (United States)

    Hehle, Verena K; Lombardi, Raffaele; van Dolleweerd, Craig J; Paul, Mathew J; Di Micco, Patrizio; Morea, Veronica; Benvenuto, Eugenio; Donini, Marcello; Ma, Julian K-C

    2015-02-01

    Plants are promising hosts for the production of monoclonal antibodies (mAbs). However, proteolytic degradation of antibodies produced both in stable transgenic plants and using transient expression systems is still a major issue for efficient high-yield recombinant protein accumulation. In this work, we have performed a detailed study of the degradation profiles of two human IgG1 mAbs produced in plants: an anti-HIV mAb 2G12 and a tumour-targeting mAb H10. Even though they use different light chains (κ and λ, respectively), the fragmentation pattern of both antibodies was similar. The majority of Ig fragments result from proteolytic degradation, but there are only a limited number of plant proteolytic cleavage events in the immunoglobulin light and heavy chains. All of the cleavage sites identified were in the proximity of interdomain regions and occurred at each interdomain site, with the exception of the VL /CL interface in mAb H10 λ light chain. Cleavage site sequences were analysed, and residue patterns characteristic of proteolytic enzymes substrates were identified. The results of this work help to define common degradation events in plant-produced mAbs and raise the possibility of predicting antibody degradation patterns 'a priori' and designing novel stabilization strategies by site-specific mutagenesis. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  7. 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

  8. 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

  9. Differentiation of foot-and-mouth disease virus infected animals from vaccinated animals using a blocking ELISA based on baculovirus expressed FMDV 3ABC antigen and a 3ABC monoclonal antibody

    DEFF Research Database (Denmark)

    Sørensen, K.J.; de Stricker, K.; Dyrting, K.C.

    2005-01-01

    A blocking ELISA that differentiated foot-and-mouth disease virus (FMDV) infected animals from vaccinated animals was developed which uses baculovirus expressed FMDV 3ABC non-structural protein as antigen and monoclonal antibody against FMDV 3ABC non-structural protein as capture and detector...... and sheep collected after experimental or natural infection. The blocking ELISA based on recombinant FMDV 3ABC antigen and a monoclonal antibody to 3ABC is a promising tool for FMD control and eradication campaigns, where vaccination has been carried out....

  10. The promising opportunity of dismantlement

    International Nuclear Information System (INIS)

    Anon.

    2009-01-01

    Civil engineering, mechanics and waste conditioning companies are thriving around the market of nuclear facilities dismantlement which is promised to a huge development in the coming decade. This paper presents a map of the opportunities of the dismantlement market throughout Europe (research and power reactors, fuel fabrication plants, spent fuel reprocessing plants) and a cost estimation of a given dismantling work with respect to the different steps of the work. In France a small core of about twenty companies is involved in nuclear dismantlement but the French market is also looking towards foreign specialists of this activity. The British market is also targeted by the French companies but for all the actors the technological or commercial advance gained today will be determining for the future markets. (J.S.)

  11. Anticorpos neutralizantes contra o vírus da Diarréia Viral Bovina (BVDV: comparação entre um imunógeno experimental atenuado e três vacinas comerciais inativadas Vaccination-induced neutralizing antibodies against bovine viral diarrhea virus (BVDV: comparison between an experimental modified-live vaccine and three comercial inactivated vaccines

    Directory of Open Access Journals (Sweden)

    Marcelo de Lima

    2005-02-01

    Full Text Available Os títulos e duração de anticorpos neutralizantes contra o vírus da Diarréia Viral Bovina (BVDV induzidos por uma vacina experimental atenuada (vacina A: dose única foram comparados com os induzidos por três vacinas comerciais inativadas (B, C e D: duas doses com intervalo de 30 dias. Trinta dias após a vacinação (vacina A ou após a segunda dose (vacinas B, C e D, anticorpos neutralizantes contra o BVDV-1 foram detectados em todos os animais (12/12 do grupo A (título médio geométrico GMT=1612,7; em 32 de 36 animais do grupo B (GMT=14,3; 22 de 28 do grupo C (GMT=25,1; e em 16 de 30 do grupo D (GMT=40,0. Anticorpos frente ao BVDV-2 foram detectados em todos os animais do grupo A (GMT=151,0; em 27 de 36 do grupo B (GMT=10,0; 12 de 28 do grupo C (GMT=11,5 e em 10 de 30 animais do grupo D (GMT=10,0. No dia 180 após a vacinação, o número de animais que ainda apresentava anticorpos contra o BVDV-1 e os GMTs para cada grupo foram: vacina A (12/12, GMT=905,0; vacina B (30/36, GMT=28,3; vacina C (20/28, GMT=28,3; vacina D (14/30, GMT=16,1; e contra o BVDV-2 foram: vacina A (12/12, GMT=56,6; vacina B (18/36, GMT=16,8; vacina C (10/28, GMT=21,6 e vacina D (6/30, GMT=16,1. Os títulos médios (GMTs induzidos pela vacina A foram significativamente superiores aos demais, tanto para o BVDV-1 (PThe titers and duration of neutralizing antibodies against bovine viral diarrhea virus (BVDV induced by an experimental attenuated vaccine (vaccine A: one dose were compared to those induced by three commercial inactivated ones (B, C and D: two doses at a 30 day interval. Thirty days after vaccination (vaccine A or the second dose (vaccines B, C and D, neutralizing antibodies to BVDV-1 were detected in all calves (12/12 from group A (mean geometric titer GMT=1612.7; in 32 out of 36 from group B (GMT=14.3; 22/28 from group C (GMT=25.1; 16/30 from group D (GMT=40.0. Antibodies reacting with BVDV-2 were detected in all animals from group A (GMT=151.0; 27

  12. Antibody response against gastrointestinal antigens in demyelinating diseases of the central nervous system

    DEFF Research Database (Denmark)

    Banati, M; Csecsei, P; Koszegi, E

    2013-01-01

    BACKGROUND: Antibodies against gastrointestinal antigens may indicate altered microbiota and immune responses in the gut. Recent experimental data suggest a connection between gastrointestinal immune responses and CNS autoimmunity. METHODS: Antibodies against gliadin, tissue transglutaminase (tTG...

  13. 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.

  14. Recent Progress towards Engineering HIV-1-specific Neutralizing Monoclonal Antibodies

    Directory of Open Access Journals (Sweden)

    Ming Sun

    2016-09-01

    Full Text Available The recent discoveries of broadly potent neutralizing human monoclonal antibodies (bNAbs represent a new generation of antiretrovirals for the treatment and prophylaxis. Antibodies are generally considered more effective and safer, and have been proved to provide passive protection against mucosal challenge in humanized mice and macaques. Several neutralizing Abs could protect animals against HIV-1 but are not effective when used in an established infected model for therapy. In order to overcome the limitation of antiviral activities, multiple antibody engineering technologies have been explored to generate the better neutralizing antibodies against HIV-1 since bNAbs attack viral entry by various mechanisms. Thus, a promising direction of research is to discover and exploit rational antibody combination or engineered antibodies (eAbs as potential candidate therapeutics against HIV-1. It has been reported that inclusion of fusion-neutralizing antibodies in a set of bNAbs could improve their overall activities and neutralizing spectrum. Here we review several routes for engineering bNAbs, such as design and generation of bispecific antibodies, specific glycosylation of antibodies to enhance antiviral activity, and variable region specific modification guided by structure and computer, as well as reviewing antibody-delivery technologies by non-viral vector, viral vector and human HSPCs transduced with a lentiviral construct. We also discuss the optimized antiviral activities and benefits of these strategy and potential mechanisms.

  15. Resveratrol analogs: promising chemopreventive agents.

    Science.gov (United States)

    Ogas, Talysa; Kondratyuk, Tamara P; Pezzuto, John M

    2013-07-01

    Although resveratrol can modulate multiple stages of carcinogenesis, by most common standards it is not a good drug candidate. Resveratrol lacks potency, high efficacy, and target specificity; it is rapidly metabolized and serum concentrations are low. Using resveratrol as a scaffold, we produced over 100 derivatives, some of which have target specificity in the nanomolar range. Aromatase inhibition was enhanced over 6000-fold by using 1,3-thiazole as the central ring of resveratrol. Optimizing the substitution pattern of the two phenyl rings and the central heterocyclic linker led to selective QR1 induction with a CD value of 87 nM. Several derivatives have been selected for evaluation of synergistic effects. Preliminary results with pairs of compounds are promising and further experiments, in a constant multidrug manner, will allow us to create polygonograms for larger combinations of derivatives. The objective is to develop a highly efficacious cocktail of derivatives based on the structure of resveratrol. © 2013 New York Academy of Sciences.

  16. Why do promises affect trustworthiness, or do they?

    NARCIS (Netherlands)

    Ismayilov, Huseyn; Potters, Jan

    2016-01-01

    We set out to test whether the effect of promises on trustworthiness derives from the fact that they are made (internal consistency) or that they are received (social obligation). The results of an experimental trust game appeared at first to support the former mechanism. Even when trustee messages

  17. Functional Role for Humoral Antibodies in Leishmaniasis in Laboratory Animals.

    Science.gov (United States)

    1980-01-01

    increases in phagocytosis by immune serum, as in rodent malaria (22, 23), have been shown. In Trypanosoma cruzi infection in mice, enhanced protection...Protective effects of specific antibodies in Trypanosoma cruzi infections. J. Immunol. 116:755-760. 26. Kierszenbaum, F., and J.G. Howard. 1976...Mechanisms of resistance against experimental Trypanosoma cruzi infection: the importance of antibodies and antibody-forming capacity in the Biozzi high

  18. Quinoline: a promising antitubercular target.

    Science.gov (United States)

    Keri, Rangappa S; Patil, Siddappa A

    2014-10-01

    Tuberculosis (TB) remains a global public health problem in recent years. TB originated mainly from various strains of Mycobacterium tuberculosis, is a highly infectious and chronic disease with high infection rate since ancient times. Since the last 50 years, the same long-duration, multidrug treatment plan is being followed for the treatment of tuberculosis. Due to the development of resistance to conventional antibiotics there is a need for new therapeutic strategies to combat M. tuberculosis. Subsequently, there is an urgent need for the development of new drug molecules with newer targets and with an alternative mechanism of action. Among hetrocyclic compounds, quinoline compounds are important privileged structure in medicinal chemistry, are widely used as "parental" compounds to synthesize molecules with medical benefits, especially with anti-malarial and anti-microbial activities. Certain, quinoline-based compounds, also show effective anti-TB activity. This broad spectrum of biological and biochemical activities has been further facilitated by the synthetic versatility of quinoline, which allows the generation of a large number of structurally diverse derivatives. To pave the way for future research, there is a need to collect the latest information in this promising area. In the present review, we have collated published reports on this versatile core to provide an insight so that its full therapeutic potential can be utilized for the treatment tuberculosis. It is hoped that, this review will be helpful for new thoughts in the quest for rational designs of more active and less toxic quinoline-based anti-TB drugs. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  19. 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

  20. Antibodies Against Melanin

    African Journals Online (AJOL)

    1973-01-06

    Jan 6, 1973 ... Departments of Internal Medicine and Anatomical Pathology, University of Stellenbosch and MRC. Pigment Metabolism Research Unit, ... at the production of antibodies against natural melanoprotein. and a consideration of our negative .... the random polymerization of several monomers, antibody formed ...

  1. Recombinant renewable polyclonal antibodies.

    Science.gov (United States)

    Ferrara, Fortunato; D'Angelo, Sara; Gaiotto, Tiziano; Naranjo, Leslie; Tian, Hongzhao; Gräslund, Susanne; Dobrovetsky, Elena; Hraber, Peter; Lund-Johansen, Fridtjof; Saragozza, Silvia; Sblattero, Daniele; Kiss, Csaba; Bradbury, Andrew R M

    2015-01-01

    Only a small fraction of the antibodies in a traditional polyclonal antibody mixture recognize the target of interest, frequently resulting in undesirable polyreactivity. Here, we show that high-quality recombinant polyclonals, in which hundreds of different antibodies are all directed toward a target of interest, can be easily generated in vitro by combining phage and yeast display. We show that, unlike traditional polyclonals, which are limited resources, recombinant polyclonal antibodies can be amplified over one hundred million-fold without losing representation or functionality. Our protocol was tested on 9 different targets to demonstrate how the strategy allows the selective amplification of antibodies directed toward desirable target specific epitopes, such as those found in one protein but not a closely related one, and the elimination of antibodies recognizing common epitopes, without significant loss of diversity. These recombinant renewable polyclonal antibodies are usable in different assays, and can be generated in high throughput. This approach could potentially be used to develop highly specific recombinant renewable antibodies against all human gene products.

  2. Studies of monoclonal antibodies IOR-CEA-1 and IOR-EGF/R3 labelled with 99mTc

    International Nuclear Information System (INIS)

    Dias, Carla Roberta de Barros Rodrigues

    2005-01-01

    Nuclear Medicine is a speciality that uses radioisotopes for the diagnosis or treatment of diseases and it is considered one of the best tools among the diagnostic modalities for detection of cancer. 99m Tc is one of the main isotopes for labelling antibodies and in Nuclear Medicine in general, due to its adequate physical properties, availability and low cost. Labelled monoclonal antibodies have shown promising results for diagnosis and therapy of cancer and their use has brought great experimental and clinical advances in the field of oncology. The main clinical applications of immunoscintigraphy with monoclonal antibodies are staging and evaluation of tumoral reappearance. The antibodies employed in this work were: OIR-CEA-1, a murine monoclonal antibody that acts directly against CEA expressed in several neoplasia in particular those from the gastrointestinal tract (colorectal cancer) and IOR-EGF/R3, a murine monoclonal antibody that binds to the external domain of EGF-R and it has been used in the diagnosis of tumors of epithelial origin. The objectives of this work were the development and optimization of the reduction and purification processes, the radiolabelling techniques and quality control procedures (radiochemical, immunoreactivity and cystein challenge) and imaging studies of monoclonal antibodies OIR-CEA-1 and IOR-EGF/R3, using the simple, fast and efficient method of direct labelling of the antibody with 99m Tc. The final results was the definition of the best conditions for the preparation of lyophilized reactive kits of OIR-CEA-1 and IOR- EGF/R3 for an efficient diagnostic application in Nuclear Medicine. The most adequate conditions for the labelling of the antibodies were: 1.0 mg Ab, 29 μL MDP, 3.0 μg Sn 2+ , 1 mL of 99m Tc and 30 min. reaction time. With these conditions the labelling yield was always higher than 95% and the maximum activity of 99m Tc was about 2220 MBq (60 mCi). The evidences of the efficiency and quality of the methods here

  3. Antibody-Mediated Catalysis in Infection and Immunity.

    Science.gov (United States)

    Bowen, Anthony; Wear, Maggie; Casadevall, Arturo

    2017-09-01

    The existence of catalytic antibodies has been known for decades. Natural antibodies capable of cleaving nucleic acid, protein, and polysaccharide substrates have been described. Although the discovery of catalytic antibodies initially aroused great interest because of their promise for the development of new catalysts, their enzymatic performance has been disappointing due to low reaction rates. However, in the areas of infection and immunity, where processes often occur over much longer times and involve high antibody concentrations, even low catalytic rates have the potential to influence biological outcomes. In this regard, the presence of catalytic antibodies recognizing host antigens has been associated with several autoimmune diseases. Furthermore, naturally occurring catalytic antibodies to microbial determinants have been correlated with resistance to infection. Recently, there has been substantial interest in harnessing the power of antibody-mediated catalysis against microbial antigens for host defense. Additional work is needed, however, to better understand the prevalence, function, and structural basis of catalytic activity in antibodies. Here we review the available information and suggest that antibody-mediated catalysis is a fertile area for study with broad applications in infection and immunity. Copyright © 2017 American Society for Microbiology.

  4. 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...

  5. Anti-insulin antibody test

    Science.gov (United States)

    Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... You appear to have an allergic response to insulin Insulin no longer seems to control your diabetes

  6. Bispecific antibodies and their use in applied research

    Directory of Open Access Journals (Sweden)

    Harshit Verma

    Full Text Available Bispecific antibodies (BsAb can, by virtue of combining two binding specificities, improve the selectivity and efficacy of antibody-based treatment of human disease. Antibodies with two distinct binding specificities have great potential for a wide range of clinical applications as targeting agents for in vitro and in vivo immunodiagnosis, therapy and for improving immunoassays. They have shown great promise for targeting cytotoxic effector cells, delivering radionuclides, toxins or cytotoxic drugs to specific targets, particularly tumour cells. The development of BsAb research goes through three main stages: chemical cross linking of murine-derived monoclonal antibody, hybrid hybridomas and engineered BsAb. This article is providing the potential applications of bispecific antibodies. [Vet World 2012; 5(12.000: 775-780

  7. Monoclonal antibody "gold rush".

    Science.gov (United States)

    Maggon, Krishan

    2007-01-01

    The market, sales and regulatory approval of new human medicines, during the past few years, indicates increasing number and share of new biologics and emergence of new multibillion dollar molecules. The global sale of monoclonal antibodies in 2006 were $20.6 billion. Remicade had annual sales gain of $1 billion during the past 3 years and five brands had similar increase in 2006. Rituxan with 2006 sales of $4.7 billion was the best selling monoclonal antibody and biological product and the 6th among the top selling medicinal brand. It may be the first biologic and monoclonal antibody to reach $10 billion annual sales in the near future. The strong demand from cancer and arthritis patients has surpassed almost all commercial market research reports and sales forecast. Seven monoclonal antibody brands in 2006 had sales exceeding $1 billion. Humanized or fully human monoclonal antibodies with low immunogenicity, enhanced antigen binding and reduced cellular toxicity provide better clinical efficacy. The higher technical and clinical success rate, overcoming of technical hurdles in large scale manufacturing, low cost of market entry and IND filing, use of fully human and humanized monoclonal antibodies has attracted funds and resources towards R&D. Review of industry research pipeline and sales data during the past 3 years indicate a real paradigm shift in industrial R&D from pharmaceutical to biologics and monoclonal antibodies. The antibody bandwagon has been joined by 200 companies with hundreds of new projects and targets and has attracted billions of dollars in R&D investment, acquisitions and licensing deals leading to the current Monoclonal Antibody Gold Rush.

  8. Mathematical modeling based on ordinary differential equations: A promising approach to vaccinology.

    Science.gov (United States)

    Bonin, Carla Rezende Barbosa; Fernandes, Guilherme Cortes; Dos Santos, Rodrigo Weber; Lobosco, Marcelo

    2017-02-01

    New contributions that aim to accelerate the development or to improve the efficacy and safety of vaccines arise from many different areas of research and technology. One of these areas is computational science, which traditionally participates in the initial steps, such as the pre-screening of active substances that have the potential to become a vaccine antigen. In this work, we present another promising way to use computational science in vaccinology: mathematical and computational models of important cell and protein dynamics of the immune system. A system of Ordinary Differential Equations represents different immune system populations, such as B cells and T cells, antigen presenting cells and antibodies. In this way, it is possible to simulate, in silico, the immune response to vaccines under development or under study. Distinct scenarios can be simulated by varying parameters of the mathematical model. As a proof of concept, we developed a model of the immune response to vaccination against the yellow fever. Our simulations have shown consistent results when compared with experimental data available in the literature. The model is generic enough to represent the action of other diseases or vaccines in the human immune system, such as dengue and Zika virus.

  9. Antibody affinity maturation

    DEFF Research Database (Denmark)

    Skjødt, Mette Louise

    surface expression of various antibody formats in the generated knockout strain. Functional scFv and scFab fragments were efficiently displayed on yeast whereas impaired chain assembly and heavy chain degradation was observed for display of full-length IgG molecules. To identify the optimal polypeptide......-antibody interface and the antibody intraface.the microenvironment and ecology of Acaryochloris and Prochloron, and in this thesis we attempted to further describe the distribution, growth characteristics and adaptive/regulatory mechanisms of these two cyanobacteria, both in their natural habitat and under defined...

  10. Immunotherapy and immunochemotherapy in visceral leishmaniasis: promising treatments for this neglected disease

    Directory of Open Access Journals (Sweden)

    Bruno Mendes Roatt

    2014-06-01

    Full Text Available Leishmaniasis has several clinical forms: self-healing or chronic cutaneous leishmaniasis or post-kala-azar dermal leishmaniasis; mucosal leishmaniasis; and visceral leishmaniasis, which is fatal if left untreated. The epidemiology and clinical features of VL vary greatly due to the interaction of multiple factors including parasite strains, vectors, host genetics, and the environment. HIV infection, augments the severity of VL increasing the risk of developing active disease by 100 to 2320 times. An effective vaccine for humans is not yet available. Resistance to chemotherapy is a growing problem in many regions, and the costs associated with drug identification and development, make commercial production for leishmaniasis, unattractive. The toxicity of currently drugs, their long treatment course, and limited efficacy are significant concerns. For cutaneous disease, many studies have shown promising results with immunotherapy/immunochemotherapy, aimed to modulate and activate the immune response to obtain a therapeutic cure. Nowadays, the focus of many groups centers on treating canine VL by using vaccines and immunomodulators with or without chemotherapy. In human disease, the use of cytokines like Interferon-γ associated with pentavalent antimonials demonstrated promising results in patients that did not respond to conventional treatment. In mice, immunomodulation based on monoclonal antibodies to remove endogenous immunosuppressive cytokines (interleukin-10 or block their receptors, antigen-pulsed syngeneic dendritic cells, or biological products like Pam3Cys (TLR ligand has already been shown as a prospective treatment of the disease. This review addresses VL treatment, particularly immunotherapy and/or immunochemotherapy as an alternative to conventional drug treatment in experimental models, canine VL, and human disease.

  11. 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 ...

  12. Anti-sulfotyrosine antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Bertozzi, Carolyn R [Berkeley, CA; Kehoe, John [Saint Davids, PA; Bradbury, Andrew M [Santa Fe, NM

    2009-09-15

    The invention provides anti-sulfotyrosine specific antibodies capable of detecting and isolating polypeptides that are tyrosine-sulfated. The sulfotyrosine antibodies and antibody fragments of the invention may be used to discriminate between the non-sulfated and sulfated forms of such proteins, using any number of immunological assays, such ELISAs, immunoblots, Western Blots, immunoprecipitations, and the like. Using a phage-display system, single chain antibodies (scFvs) were generated and screened against tyrosine-sulfated synthetic peptide antigens, resulting in the isolation of scFvs that specifically recognize sulfotyrosine-containing peptides and/or demonstrate sulfotyrosine-specific binding in tyrosine sulfated proteins. The VH and VL genes from one such sulfotyrosine-specific scFv were employed to generate a full length, sulfotyrosine-specific immunoglobulin.

  13. Bifunctional antibodies for radioimmunotherapy.

    Science.gov (United States)

    Chatal, J F; Faivre-Chauvet, A; Bardies, M; Peltier, P; Gautherot, E; Barbet, J

    1995-04-01

    In two-step targeting technique using bifunctional antibodies, a nonradiolabeled immunoconjugate with slow uptake kinetics (several days) is initially injected, followed by a small radiolabeled hapten with fast kinetics (several hours) that binds to the bispecific immunoconjugate already taken up by the tumor target. In patients with colorectal or medullary thyroid cancer, clinical studies performed with an anti-CEA/anti-DTPA-indium bifunctional antibody and an indium-111-labeled di-DTPA-TL bivalent hapten showed that tumor uptake was not modified compared to results for F(ab')2 fragments of the same anti-CEA antibody directly labeled with indium-111, whereas the radioactivity of normal tissues was significantly reduced (3- to 6-fold). The fast tumor uptake kinetics (several hours) and high or very high tumor-to-normal tissue ratios obtained with the bifunctional antibody technique are favorable parameters for efficient radioimmunotherapy.

  14. Antibody Blood Tests

    Science.gov (United States)

    Antibody Blood Tests Researchers have discovered that people with celiac disease who eat gluten have higher than normal levels of ... do I do if I have a negative blood test (or panel) but I’m still having symptoms? ...

  15. The Position of His-Tag in Recombinant OspC and Application of Various Adjuvants Affects the Intensity and Quality of Specific Antibody Response after Immunization of Experimental Mice.

    Directory of Open Access Journals (Sweden)

    Michal Krupka

    Full Text Available Lyme disease, Borrelia burgdorferi-caused infection, if not recognized and appropriately treated by antibiotics, may lead to chronic complications, thus stressing the need for protective vaccine development. The immune protection is mediated by phagocytic cells and by Borrelia-specific complement-activating antibodies, associated with the Th1 immune response. Surface antigen OspC is involved in Borrelia spreading through the host body. Previously we reported that recombinant histidine tagged (His-tag OspC (rOspC could be attached onto liposome surfaces by metallochelation. Here we report that levels of OspC-specific antibodies vary substantially depending upon whether rOspC possesses an N' or C' terminal His-tag. This is the case in mice immunized: (a with rOspC proteoliposomes containing adjuvants MPLA or non-pyrogenic MDP analogue MT06; (b with free rOspC and Montanide PET GEL A; (c with free rOspC and alum; or (d with adjuvant-free rOspC. Stronger responses are noted with all N'-terminal His-tag rOspC formulations. OspC-specific Th1-type antibodies predominate post-immunization with rOspC proteoliposomes formulated with MPLA or MT06 adjuvants. Further analyses confirmed that the structural features of soluble N' and C' terminal His-tag rOspC and respective rOspC proteoliposomes are similar including their thermal stabilities at physiological temperatures. On the other hand, a change in the position of the rOspC His-tag from N' to C' terminal appears to affect substantially the immunogenicity of rOspC arguably due to steric hindrance of OspC epitopes by the C' terminal His-tag itself and not due to differences in overall conformations induced by changes in the His-tag position in rOspC variants.

  16. Monoclonal Antibody: A New Treatment Strategy against Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Shih-Feng Cho

    2017-11-01

    Full Text Available 2015 was a groundbreaking year for the multiple myeloma community partly due to the breakthrough approval of the first two monoclonal antibodies in the treatment for patients with relapsed and refractory disease. Despite early disappointments, monoclonal antibodies targeting CD38 (daratumumab and signaling lymphocytic activation molecule F7 (SLAMF7 (elotuzumab have become available for patients with multiple myeloma in the same year. Specifically, phase 3 clinical trials of combination therapies incorporating daratumumab or elotuzumab indicate both efficacy and a very favorable toxicity profile. These therapeutic monoclonal antibodies for multiple myeloma can kill target cells via antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent phagocytosis, as well as by direct blockade of signaling cascades. In addition, their immunomodulatory effects may simultaneously inhibit the immunosuppressive bone marrow microenvironment and restore the key function of immune effector cells. In this review, we focus on monoclonal antibodies that have shown clinical efficacy or promising preclinical anti-multiple myeloma activities that warrant further clinical development. We summarize mechanisms that account for the in vitro and in vivo anti-myeloma effects of these monoclonal antibodies, as well as relevant preclinical and clinical results. Monoclonal antibody-based immunotherapies have already and will continue to transform the treatment landscape in multiple myeloma.

  17. Cell-Free Synthesis Meets Antibody Production: A Review

    Directory of Open Access Journals (Sweden)

    Marlitt Stech

    2015-01-01

    Full Text Available Engineered antibodies are key players in therapy, diagnostics and research. In addition to full size immunoglobulin gamma (IgG molecules, smaller formats of recombinant antibodies, such as single-chain variable fragments (scFv and antigen binding fragments (Fab, have emerged as promising alternatives since they possess different advantageous properties. Cell-based production technologies of antibodies and antibody fragments are well-established, allowing researchers to design and manufacture highly specific molecular recognition tools. However, as these technologies are accompanied by the drawbacks of being rather time-consuming and cost-intensive, efficient and powerful cell-free protein synthesis systems have been developed over the last decade as alternatives. So far, prokaryotic cell-free systems have been the focus of interest. Recently, eukaryotic in vitro translation systems have enriched the antibody production pipeline, as these systems are able to mimic the natural pathway of antibody synthesis in eukaryotic cells. This review aims to overview and summarize the advances made in the production of antibodies and antibody fragments in cell-free systems.

  18. 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.

  19. Neutralization of botulinum neurotoxin by a human monoclonal antibody specific for the catalytic light chain.

    Directory of Open Access Journals (Sweden)

    Sharad P Adekar

    2008-08-01

    Full Text Available Botulinum neurotoxins (BoNT are a family of category A select bioterror agents and the most potent biological toxins known. Cloned antibody therapeutics hold considerable promise as BoNT therapeutics, but the therapeutic utility of antibodies that bind the BoNT light chain domain (LC, a metalloprotease that functions in the cytosol of cholinergic neurons, has not been thoroughly explored.We used an optimized hybridoma method to clone a fully human antibody specific for the LC of serotype A BoNT (BoNT/A. The 4LCA antibody demonstrated potent in vivo neutralization when administered alone and collaborated with an antibody specific for the HC. In Neuro-2a neuroblastoma cells, the 4LCA antibody prevented the cleavage of the BoNT/A proteolytic target, SNAP-25. Unlike an antibody specific for the HC, the 4LCA antibody did not block entry of BoNT/A into cultured cells. Instead, it was taken up into synaptic vesicles along with BoNT/A. The 4LCA antibody also directly inhibited BoNT/A catalytic activity in vitro.An antibody specific for the BoNT/A LC can potently inhibit BoNT/A in vivo and in vitro, using mechanisms not previously associated with BoNT-neutralizing antibodies. Antibodies specific for BoNT LC may be valuable components of an antibody antidote for BoNT exposure.

  20. Sequential immunohistochemistry: a promising new tool for the pathology laboratory.

    Science.gov (United States)

    van den Brand, Michiel; Hoevenaars, Brigiet M; Sigmans, Jessica H M; Meijer, Jos W R; van Cleef, Patricia H J; Groenen, Patricia J T A; Hebeda, Konnie M; van Krieken, J Han J M

    2014-11-01

    Current immunohistochemical methods to study the expression of multiple proteins in a single tissue section suffer from several limitations. In this article, we report on sequential immunohistochemistry (S-IHC), a novel, easy method that allows the study of numerous proteins in a single tissue section, while requiring very limited optimization. In S-IHC, a tissue section is stained for multiple antibodies, with intermediate scanning of the section and elution of chromogen and antibodies. Overlays are made of the digital images, allowing assessment of multiple proteins in the same tissue section. We used S-IHC to study nine nodular lymphocyte-predominant Hodgkin lymphomas (NLPHLs) and 10 T-cell-rich and histiocyte-rich diffuse large B-cell lymphomas (T/HRBCLs) for expression of cyclin D1, CD20, and CD68. We observed cyclin D1 expression in single tumour cells in 44% of NLPHLs and 60% of T/HRBCLs. Comparison of S-IHC with classic single immunohistochemical staining revealed discrepancies in eight cases (42%), demonstrating the difficulty of differentiating tumour cells from histiocytes on morphological grounds, and stressing the additional value of S-IHC. For research and diagnostic purposes, S-IHC is a promising technique that assesses the expression of numerous proteins in single tissue sections with complete architectural information, allowing phenotypic characterization of single cells. © 2014 John Wiley & Sons Ltd.

  1. A rate-limiting role for Dickkopf-1 in bone formation and the remediation of bone loss in mouse and primate models of postmenopausal osteoporosis by an experimental therapeutic antibody.

    Science.gov (United States)

    Glantschnig, Helmut; Scott, Kevin; Hampton, Richard; Wei, Nan; McCracken, Paul; Nantermet, Pascale; Zhao, Jing Z; Vitelli, Salvatore; Huang, Lingyi; Haytko, Peter; Lu, Ping; Fisher, John E; Sandhu, Punam; Cook, Jacquelynn; Williams, Donald; Strohl, William; Flores, Osvaldo; Kimmel, Donald; Wang, Fubao; An, Zhiqiang

    2011-08-01

    Genetic studies have linked both osteoporotic and high bone mass phenotypes to low-density lipoprotein receptor-related proteins (LRP4, LRP5, and LRP6). LRPs are receptors for inhibitory Dickkopf-1 (DKK1) protein, and treatment modalities that modulate LRP/DKK1 binding therefore may act as stimulators of bone mass accrual. Here, we report that RH2-18, a fully human monoclonal anti-DKK1 antibody elicits systemic pharmacologic bone efficacy and new bone formation at endosteal bone surfaces in vivo in a mouse model of estrogen-deficiency-induced osteopenia. This was paralleled by partial-to-complete resolution of osteopenia (bone mineral density) at all of the skeletal sites investigated in femur and lumbar-vertebral bodies and the restoration of trabecular bone microarchitecture. More importantly, testing of RH2-18 in adult, osteopenic rhesus macaques demonstrated a rate-limiting role of DKK1 at multiple skeletal sites and responsiveness to treatment. In conclusion, this study provides pharmacologic evidence for the modulation of DKK1 bioactivity in the adult osteopenic skeleton as a viable approach to resolve osteopenia in animal models. Thus, data described here suggest that targeting DKK1 through means such as a fully human anti-DKK1-antibody provides a potential bone-anabolic treatment for postmenopausal osteoporosis.

  2. Single Domain Antibodies as New Biomarker Detectors

    Science.gov (United States)

    Fischer, Katja; Leow, Chiuan Yee; Chuah, Candy; McCarthy, James

    2017-01-01

    Biomarkers are defined as indicators of biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. Biomarkers have been widely used for early detection, prediction of response after treatment, and for monitoring the progression of diseases. Antibodies represent promising tools for recognition of biomarkers, and are widely deployed as analytical tools in clinical settings. For immunodiagnostics, antibodies are now exploited as binders for antigens of interest across a range of platforms. More recently, the discovery of antibody surface display and combinatorial chemistry techniques has allowed the exploration of new binders from a range of animals, for instance variable domains of new antigen receptors (VNAR) from shark and variable heavy chain domains (VHH) or nanobodies from camelids. These single domain antibodies (sdAbs) have some advantages over conventional murine immunoglobulin owing to the lack of a light chain, making them the smallest natural biomarker binders thus far identified. In this review, we will discuss several biomarkers used as a means to validate diseases progress. The potential functionality of modern singe domain antigen binders derived from phylogenetically early animals as new biomarker detectors for current diagnostic and research platforms development will be described. PMID:29039819

  3. Single Domain Antibodies as New Biomarker Detectors

    Directory of Open Access Journals (Sweden)

    Chiuan Herng Leow

    2017-10-01

    Full Text Available Biomarkers are defined as indicators of biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. Biomarkers have been widely used for early detection, prediction of response after treatment, and for monitoring the progression of diseases. Antibodies represent promising tools for recognition of biomarkers, and are widely deployed as analytical tools in clinical settings. For immunodiagnostics, antibodies are now exploited as binders for antigens of interest across a range of platforms. More recently, the discovery of antibody surface display and combinatorial chemistry techniques has allowed the exploration of new binders from a range of animals, for instance variable domains of new antigen receptors (VNAR from shark and variable heavy chain domains (VHH or nanobodies from camelids. These single domain antibodies (sdAbs have some advantages over conventional murine immunoglobulin owing to the lack of a light chain, making them the smallest natural biomarker binders thus far identified. In this review, we will discuss several biomarkers used as a means to validate diseases progress. The potential functionality of modern singe domain antigen binders derived from phylogenetically early animals as new biomarker detectors for current diagnostic and research platforms development will be described.

  4. Monoclonal antibodies in animal production : their use in diagnostics and passive immunization

    NARCIS (Netherlands)

    Booman, P.

    1989-01-01

    One of the landmarks in immunology was the invention and development of monoclonal antibody-secreting hybridomas by Milstein and his coworkers. The enormous promise of monoclonal antibody technology, which became apparent soon after its discovery, may explain the unusual speed with which monoclonal

  5. 76 FR 13152 - Promise Neighborhoods Program

    Science.gov (United States)

    2011-03-10

    ... to attain an excellent education and successfully transition to college and a career. A Promise... parents or family members who report talking with their child about the importance of college and career... DEPARTMENT OF EDUCATION RIN 1855-ZA07 Promise Neighborhoods Program Catalog of Federal Domestic...

  6. Tennessee Promise: A Response to Organizational Change

    Science.gov (United States)

    Littlepage, Ben; Clark, Teresa; Wilson, Randal; Stout, Logan

    2018-01-01

    Community colleges in Tennessee, either directly or indirectly, experienced unprecedented change as a result of Tennessee Promise. The present study explored how student support service administrators at three community colleges responded to organizational change as a result of the Tennessee Promise legislation. Investigators selected community…

  7. Neurofilament light as an immune target for pathogenic antibodies.

    Science.gov (United States)

    Puentes, Fabiola; van der Star, Baukje J; Boomkamp, Stephanie D; Kipp, Markus; Boon, Louis; Bosca, Isabel; Raffel, Joel; Gnanapavan, Sharmilee; van der Valk, Paul; Stephenson, Jodie; Barnett, Susan C; Baker, David; Amor, Sandra

    2017-12-01

    Antibodies to neuronal antigens are associated with many neurological diseases including paraneoplastic neurological disorders, epilepsy, amyotrophic lateral sclerosis and multiple sclerosis. Immunization with neuronal antigens such as neurofilament light (NF-L), a neuronal intermediate filament in axons, has been shown to induce neurological disease and spasticity in mice. Also, although antibodies to NF-L are widely used as surrogate biomarkers of axonal injury in amyotrophic lateral sclerosis and multiple sclerosis, it remains to be elucidated if antibodies to NF-L contribute to neurodegeneration and neurological disease. To address this, we examined the pathogenic role of antibodies directed to NF-L in vitro using spinal cord co-cultures and in vivo in experimental autoimmune encephalomyelitis (EAE) and optic neuritis animal models of multiple sclerosis. Here we show that peripheral injections of antibodies to NF-L augmented clinical signs of neurological disease in acute EAE, increased retinal ganglion cell loss in experimental optic neuritis and induced neurological signs following intracerebral injection into control mice. The pathogenicity of antibodies to NF-L was also observed in spinal cord co-cultures where axonal loss was induced. Taken together, our results reveal that as well as acting as reliable biomarkers of neuronal damage, antibodies to NF-L exacerbate neurological disease, suggesting that antibodies to NF-L generated during disease may also be pathogenic and play a role in the progression of neurodegeneration. © 2017 John Wiley & Sons Ltd.

  8. Inferences from counterfactual threats and promises.

    Science.gov (United States)

    Egan, Suzanne M; Byrne, Ruth M J

    2012-01-01

    We examine how people understand and reason from counterfactual threats, for example, "if you had hit your sister, I would have grounded you" and counterfactual promises, for example, "if you had tidied your room, I would have given you ice-cream." The first experiment shows that people consider counterfactual threats, but not counterfactual promises, to have the illocutionary force of an inducement. They also make the immediate inference that the action mentioned in the "if" part of the counterfactual threat and promise did not occur. The second experiment shows that people make more negative inferences (modus tollens and denial of the antecedent) than affirmative inferences (modus ponens and affirmation of the consequent) from counterfactual threats and promises, unlike indicative threats and promises. We discuss the implications of the results for theories of the mental representations and cognitive processes that underlie conditional inducements.

  9. Natural and Man-made Antibody Repertories for Antibody Discovery

    Directory of Open Access Journals (Sweden)

    Juan C eAlmagro

    2012-11-01

    Full Text Available Antibodies are the fastest-growing segment of the biologics market. The success of antibody-based drugs resides in their exquisite specificity, high potency, stability, solubility, safety and relatively inexpensive manufacturing process in comparison with other biologics. We outline here the structural studies and fundamental principles that define how antibodies interact with diverse targets. We also describe the antibody repertoires and affinity maturation mechanisms of human, mice and chickens, plus the use of novel single-domain antibodies in camelids and sharks. These species all utilize diverse evolutionary solutions to generate specific and high affinity antibodies and illustrate the plasticity of natural antibody repertoires. In addition, we discuss the multiple variations of man-made antibody repertoires designed and validated in the last two decades, which have served as tools to explore how the size, diversity and composition of a repertoire impact the antibody discovery process.

  10. Plant expression of chicken secretory antibodies derived from combinatorial libraries

    NARCIS (Netherlands)

    Wieland, W.H.; Lammers, A.; Schots, A.; Orzaéz, D.V.

    2006-01-01

    Delivery of secretory IgA antibodies (sIgA) to mucosal surfaces is a promising strategy to passively prevent infectious diseases. Plants have been proposed as biofactories for such complex immunoglobulin molecules. Recently, the molecular characterization of all four monomers of chicken sIgA (IgA

  11. Preclinical evaluation of radiolabelled nimotuzumab, a promising monoclonal antibody targeting the epidermal growth factor receptor

    Czech Academy of Sciences Publication Activity Database

    Bárta, P.; Lázníčková, A.; Lázníček, M.; Beckford, Denis R.; Beran, Miloš

    2013-01-01

    Roč. 56, č. 5 (2013), s. 280-288 ISSN 0362-4803 Grant - others:GA ČR(CZ) GAP304/10/1738 Institutional support: RVO:61389005 Keywords : radiopharmaceutical * 177Lu * 131I * nimotuzumab * EGFR * preclinical biodistribution Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 1.187, year: 2013

  12. Clinical usefulness of human-mouse chimeric Fab monoclonal antibody A7 for radioimmunoguided surgery

    International Nuclear Information System (INIS)

    Yamamoto, Kazuhito

    1999-01-01

    This study was designed to determine the clinical usefulness of radioimmunoguided surgery (RIGS) using the human-mouse chimeric Fab monoclonal antibody A7 (chA7Fab) for colorectal cancer patients. Whole murine monoclonal antibody A7 (whole A7) and chA7Fab were labelled with 125 I and 131 I, and their biodistributions were investigated experimentally and clinically. Radioactivities of the antibodies in the tissues were measured by a portable gamma detecting probe (GDP) purchased from Neoprobe Corp.. Of the four labelled antibodies used in a mouse model, 125 I-chA7Fab revealed the highest tumor/surrounding tissue ratio and all values were greater than 2.0. All tumor/surrounding tissue ratios of 131 I-chA7Fab were greater than 1.5, but the values were lower than those of 125 I-chA7Fab. Due to the limited clinical use of 125 I in Japan, 131 I was used as a radio-tracer for chA7Fab in the clinical trial. RIGS using 131 I-chA7Fab was performed on ten colorectal cancer patients. Tumor localization was intraoperatively determined in four of ten patients using the GDP. Liver metastasis and lymph node metastasis were identified in two patients and one patient, respectively. The GDP revealed tumor/surrounding tissue ratios of 1.5 or greater in eight of the ten resected tumors. Although radioimmunoguided surgery using chA7Fab is a promising tool to intraoperatively determine the tumor localization of colorectal cancer, 125 I and not 131 I should be used as a tracer for radioimmunoguided surgery to increase the accuracy of chA7Fab. (author)

  13. Structural biology of antibody recognition of carbohydrate epitopes and potential uses for targeted cancer immunotherapies.

    Science.gov (United States)

    Dingjan, Tamir; Spendlove, Ian; Durrant, Lindy G; Scott, Andrew M; Yuriev, Elizabeth; Ramsland, Paul A

    2015-10-01

    Monoclonal antibodies represent the most successful class of biopharmaceuticals for the treatment of cancer. Mechanisms of action of therapeutic antibodies are very diverse and reflect their ability to engage in antibody-dependent effector mechanisms, internalize to deliver cytotoxic payloads, and display direct effects on cells by lysis or by modulating the biological pathways of their target antigens. Importantly, one of the universal changes in cancer is glycosylation and carbohydrate-binding antibodies can be produced to selectively recognize tumor cells over normal tissues. A promising group of cell surface antibody targets consists of carbohydrates presented as glycolipids or glycoproteins. In this review, we outline the basic principles of antibody-based targeting of carbohydrate antigens in cancer. We also present a detailed structural view of antibody recognition and the conformational properties of a series of related tissue-blood group (Lewis) carbohydrates that are being pursued as potential targets of cancer immunotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. 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.

  15. Boosting antibody responses by targeting antigens to dendritic cells.

    Science.gov (United States)

    Caminschi, Irina; Shortman, Ken

    2012-02-01

    Delivering antigens directly to dendritic cells (DCs) in situ, by injecting antigens coupled to antibodies specific for DC surface molecules, is a promising strategy for enhancing vaccine efficacy. Enhanced cytotoxic T cell responses are obtained if an adjuvant is co-administered to activate the DC. Such DC targeting is also effective at enhancing humoral immunity, via the generation of T follicular helper cells. Depending on the DC surface molecule targeted, antibody production can be enhanced even in the absence of adjuvants. In the case of Clec9A as the DC surface target, enhanced antibody production is a consequence of the DC-restricted expression of the target molecule. Few other cells absorb the antigen-antibody construct, therefore, it persists in the bloodstream, allowing sustained antigen presentation, even by non-activated DCs. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Recent advances in the construction of antibody-drug conjugates

    Science.gov (United States)

    Chudasama, Vijay; Maruani, Antoine; Caddick, Stephen

    2016-02-01

    Antibody-drug conjugates (ADCs) comprise antibodies covalently attached to highly potent drugs using a variety of conjugation technologies. As therapeutics, they combine the exquisite specificity of antibodies, enabling discrimination between healthy and diseased tissue, with the cell-killing ability of cytotoxic drugs. This powerful and exciting class of targeted therapy has shown considerable promise in the treatment of various cancers with two US Food and Drug Administration approved ADCs currently on the market (Adcetris and Kadcyla) and approximately 40 currently undergoing clinical evaluation. However, most of these ADCs exist as heterogeneous mixtures, which can result in a narrow therapeutic window and have major pharmacokinetic implications. In order for ADCs to deliver their full potential, sophisticated site-specific conjugation technologies to connect the drug to the antibody are vital. This Perspective discusses the strategies currently used for the site-specific construction of ADCs and appraises their merits and disadvantages.

  17. Sperm antibody production in female sterility.

    Science.gov (United States)

    Mettler, L; Scheidel, P; Shirwani, D

    1974-01-01

    A review of the immunological implications in reproductive physiology is presented. Although attempts have been made to ascribe the antigenicity of semen to individual components, it has not been possible to isolate the human semen antigen responsible for infertility. In monkeys total ejaculates and seminal plasma have shown higher antigenicity than washed spermatozoa. In bulls some evidence of such antigens have been found in the seminal plasma. They are iron-binding proteins resembling lactoferrin. Most investigators have found no evidence for any participation of the ABO blood group antigens in cases of sterility. On the surface of human spermatozoa histo-incompatibility antigens have been detected. Transplantation antigens may be related to sterility. However, an immulogic tolerance of the maternal organism exists against the genetically foreign fetal tissue. Autoimmune spermagglutinating antibodies have been detected in the sera and in the seminal plasma of males with sterility. An obstruction of the seminal pathways may facilitate the production of such antibodies against retained sperm. Isoimmunity in females against seminal components has been shown in cases of sterility; however, fertile women have also been shown to have such conditions. In a group of infertile women spermagglutination activity was detected in 7.5% of cases. In another series of 46 cases with primary unexplained infertility agglutinating antibodies were found in 17.4%. Other investigators have also reported higher rates than the authors. The sperm immobilization test seems to be more sensitive than the agglutination test. No sera were found positive with both tests. With immunofluorescent techniques humoral sperm antibodies have been found to be the IgM and IgG fractions. Each acts on a different part of the spermatozoa. The only promising therapy against humoral sperm antibodies is avoidance of sperm contact over a long period of time. Reported results have been conflicting. Cortisone

  18. 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.

  19. Antiviral Therapy by HIV-1 Broadly Neutralizing and Inhibitory Antibodies

    Directory of Open Access Journals (Sweden)

    Zhiqing Zhang

    2016-11-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 infection causes acquired immune deficiency syndrome (AIDS, a global epidemic for more than three decades. HIV-1 replication is primarily controlled through antiretroviral therapy (ART but this treatment does not cure HIV-1 infection. Furthermore, there is increasing viral resistance to ART, and side effects associated with long-term therapy. Consequently, there is a need of alternative candidates for HIV-1 prevention and therapy. Recent advances have discovered multiple broadly neutralizing antibodies against HIV-1. In this review, we describe the key epitopes on the HIV-1 Env protein and the reciprocal broadly neutralizing antibodies, and discuss the ongoing clinical trials of broadly neutralizing and inhibitory antibody therapy as well as antibody combinations, bispecific antibodies, and methods that improve therapeutic efficacy by combining broadly neutralizing antibodies (bNAbs with latency reversing agents. Compared with ART, HIV-1 therapeutics that incorporate these broadly neutralizing and inhibitory antibodies offer the advantage of decreasing virus load and clearing infected cells, which is a promising prospect in HIV-1 prevention and treatment.

  20. Targeting FcRn for the modulation of antibody dynamics.

    Science.gov (United States)

    Ward, E Sally; Devanaboyina, Siva Charan; Ober, Raimund J

    2015-10-01

    The MHC class I-related receptor, FcRn, is a multitasking protein that transports its IgG ligand within and across cells of diverse origins. The role of this receptor as a global regulator of IgG homeostasis and transport, combined with knowledge of the molecular details of FcRn-IgG interactions, has led to opportunities to modulate the in vivo dynamics of antibodies and their antigens through protein engineering. Consequently, the generation of half-life extended antibodies has shown a rapid expansion over the past decade. Further, FcRn itself can be targeted by inhibitors to induce decreased levels of circulating IgGs, which could have applications in multiple clinical settings. The engineering of antibody-antigen interactions to reduce antibody-mediated buffering of soluble ligand has also developed into an active area of investigation, leading to novel antibody platforms designed to result in more effective antigen clearance. Similarly, the target-mediated elimination of antibodies by internalizing, membrane bound antigens (receptors) can be decreased using novel engineering approaches. These strategies, combined with subcellular trafficking analyses of antibody/antigen/FcRn behavior in cells to predict in vivo behavior, have considerable promise for the production of next generation therapeutics and diagnostics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Antithyroid microsomal antibody

    Science.gov (United States)

    ... that you have a higher chance of developing thyroid disease in the future. Antithyroid microsomal antibodies may be ... PA: Elsevier; 2016:chap 11. Weiss RE, Refetoff S. Thyroid function testing. In: Jameson JL, De Groot LJ, eds. Endocrinology: Adult and ... Lupus Read more ...

  2. Antibodies Targeting EMT

    Science.gov (United States)

    2017-10-01

    determine their targets on the cell. The newly discovered antibodies will then be engineered for utility as new highly specific drugs and diagnostics in...are from the aldo-keto reductase family (AKRs). Remarkably, 3 of the top 10 genes with induction in the mesenchymal TES2b cells Figure 1. Amino

  3. Monoclonal antibodies in haematopathology

    Energy Technology Data Exchange (ETDEWEB)

    Grignani, F.; Martelli, M.F.; Mason, D.Y.

    1985-01-01

    This book contains over 40 selections. Some of the titles are: Oncogene (c-myc, c-myb) amplification in acute myelogenous leukaemia; Ultrastructural characterization of leukaemic cells with monoloclonal antibodies; Origin of B-cell malignancies; Immunohistology of gut lymphomas; and Spurious evidence of lineage infidelity in monocytic leukaemia.

  4. 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...

  5. Thrombus imaging in a primate model with antibodies specific for an external membrane protein of activated platelets

    International Nuclear Information System (INIS)

    Palabrica, T.M.; Furie, B.C.; Konstam, M.A.; Aronovitz, M.J.; Connolly, R.; Brockway, B.A.; Ramberg, K.L.; Furie, B.

    1989-01-01

    The activated platelet is a potential target for the localization of thrombi in vivo since, after stimulation and secretion of granule contents, activated platelets are concentrated at sites of blood clot formation. In this study, we used antibodies specific for a membrane protein of activated platelets to detect experimental thrombi in an animal model. PADGEM (platelet activation-dependent granule-external membrane protein), a platelet alpha-granule membrane protein, is translocated to the plasma membrane during platelet activation and granule secretion. Since PADGEM is internal in unstimulated platelets, polyclonal anti-PADGEM and monoclonal KC4 antibodies do not bind to circulating resting platelets but do interact with activated platelets. Dacron graft material incubated with radiolabeled KC4 or anti-PADGEM antibodies in the presence of thrombin-activated platelet-rich plasma bound most of the antibody. Imaging experiments with 123I-labeled anti-PADGEM in baboons with an external arterial-venous Dacron shunt revealed rapid uptake in the thrombus induced by the Dacron graft; control experiments with 123I-labeled nonimmune IgG exhibited minimal uptake. Deep venous thrombi, formed by using percutaneous balloon catheters to stop blood flow in the femoral vein of baboons, were visualized with 123I-labeled anti-PADGEM. Thrombi were discernible against blood pool background activity without subtraction techniques within 1 hr. No target enhancement was seen with 123I-labeled nonimmune IgG. 123I-labeled anti-PADGEM cleared the blood pool with an initial half-disappearance time of 6 min and did not interfere with hemostasis. These results indicate that radioimmunoscintigraphy with anti-PADGEM antibodies can visualize thrombi in baboon models and is a promising technique for clinical thrombus detection in humans

  6. Interaction of Serum Antibodies from Breast Cancer Patients with Synthetic Peptides.

    Science.gov (United States)

    Podlesnykh, S V; Kolosova, E A; Shcherbakov, D N; Shaidurov, A A; Anisimov, D S; Ryazanov, M A; Johnston, S A; Shoikhet, Ya N; Petrova, V D; Lazarev, A F; Chapoval, A I

    2016-10-01

    The blood serum of tumor patients contains antibodies recognizing tumor-associated antigens and other molecular products of tumor growth. We studied the interaction of blood antibodies from breast cancer patients with synthetic peptides that were applied on the microchip surface. The serum from healthy volunteers and breast cancer patients was shown to contain antibodies that interact with various peptides. Statistically significant between-group differences were observed in the level of binding with 122 informative peptides (0.01% of the total number of peptides on a microchip). Analysis of antibodies that interact with the peptide panel holds much promise for the diagnostics of breast cancer.

  7. 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...

  8. Rapid detection of serum antibody by dual-path platform VetTB assay in white-tailed deer infected with Mycobacterium bovis.

    Science.gov (United States)

    Lyashchenko, Konstantin P; Greenwald, Rena; Esfandiari, Javan; O'Brien, Daniel J; Schmitt, Stephen M; Palmer, Mitchell V; Waters, W Ray

    2013-06-01

    Bovine tuberculosis (TB) in cervids remains a significant problem affecting farmed herds and wild populations. Traditional skin testing has serious limitations in certain species, whereas emerging serological assays showed promising diagnostic performance. The recently developed immunochromatographic dual-path platform (DPP) VetTB assay has two antigen bands, T1 (MPB83 protein) and T2 (CFP10/ESAT-6 fusion protein), for antibody detection. We evaluated the diagnostic accuracy of this test by using serum samples collected from groups of white-tailed deer experimentally inoculated with Mycobacterium bovis, M. avium subsp. paratuberculosis, or M. bovis BCG Pasteur. In addition, we used serum samples from farmed white-tailed deer in herds with no history of TB, as well as from free-ranging white-tailed deer culled during field surveillance studies performed in Michigan known to have bovine TB in the wild deer population. The DPP VetTB assay detected antibody responses in 58.1% of experimentally infected animals within 8 to 16 weeks postinoculation and in 71.9% of naturally infected deer, resulting in an estimated test sensitivity of 65.1% and a specificity of 97.8%. The higher seroreactivity found in deer with naturally acquired M. bovis infection was associated with an increased frequency of antibody responses to the ESAT-6 and CFP10 proteins, resulting in a greater contribution of these antigens, in addition to MPB83, to the detection of seropositive animals, compared with experimental M. bovis infection. Deer experimentally inoculated with either M. avium subsp. paratuberculosis or M. bovis BCG Pasteur did not produce cross-reactive antibodies that could be detected by the DPP VetTB assay. The present findings demonstrate the relatively high diagnostic accuracy of the DPP VetTB test for white-tailed deer, especially in the detection of naturally infected animals.

  9. 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

  10. 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

  11. Human papillomavirus vaccination induces neutralising antibodies in oral mucosal fluids.

    Science.gov (United States)

    Handisurya, A; Schellenbacher, C; Haitel, A; Senger, T; Kirnbauer, R

    2016-02-16

    Mucosal human papillomaviruses (HPV) are a major cause of cancers and papillomas of the anogenital and oropharyngeal tract. HPV-vaccination elicits neutralising antibodies in sera and cervicovaginal secretions and protects uninfected individuals from persistent anogenital infection and associated diseases caused by the vaccine-targeted HPV types. Whether immunisation can prevent oropharyngeal infection and diseases and whether neutralising antibodies represent the correlate of protection, is still unclear. We determined IgG and neutralising antibodies against low-risk HPV6 and high-risk HPV16/18 in sera and oral fluids from healthy females (n=20) before and after quadrivalent HPV-vaccination and compared the results with non-vaccinated controls. HPV-vaccination induced type-specific antibodies in sera and oral fluids of the vaccinees. Importantly, the antibodies in oral fluids were capable of neutralising HPV pseudovirions in vitro, indicating protection from infection. The increased neutralising antibody levels against HPV16/18 in sera and oral fluids post-vaccination correlated significantly within an individual. We provide experimental proof that HPV-vaccination elicits neutralising antibodies to the vaccine-targeted types in oral fluids. Hence, immunisation may confer direct protection against type-specific HPV infection and associated diseases of the oropharyngeal tract. Measurement of antibodies in oral fluids represents a suitable tool to assess vaccine-induced protection within the mucosal milieu of the orophayrynx.

  12. Radioimmunodetection of human melanoma tumor xenografts with human monoclonal antibodies

    International Nuclear Information System (INIS)

    Gomibuchi, Makoto; Saxton, R.E.; Lake, R.R.; Katano, Mitsuo; Irie, R.F.

    1986-01-01

    A human IgM monoclonal antibody has been established that defines a tumor-associated membrane antigen expressed on human melanoma cells. The antigen has been identified as the ganglioside GD2. In this paper, the authors describe the potential usefulness of the human monoclonal antibody for radioimaging. Nude mice bearing tumors derived from a human melanoma cell line were used as a model. Antibody activity was degradated significantly after labeling with 131 I by the use of a modified chloramine-T method. After testing various concentrations, labeled antibody of a specific activity of 2.8μCi/μg produced the best results. Balb/c nude mice bearing a GD2-positive M14 melanoma cell line were injected with 10-30μg of labeled antibody, and its radiolocalization in different organs and in the whole body were evaluated. The best tumor image was obtained on Day 6. The labeled antibody uptake ratio between tumor and muscle was 9.2:1; the ratio between tumor and liver was 1.4:1. These studies represent the first report of experimental tumor imaging with human monoclonal antibody. Human monoclonals will probably prove to be superior reagents for tumor imaging in melanoma patients if the problem of anti-body radiolysis is resolved. (author)

  13. Human papillomavirus vaccination induces neutralising antibodies in oral mucosal fluids

    Science.gov (United States)

    Handisurya, A; Schellenbacher, C; Haitel, A; Senger, T; Kirnbauer, R

    2016-01-01

    Background: Mucosal human papillomaviruses (HPV) are a major cause of cancers and papillomas of the anogenital and oropharyngeal tract. HPV-vaccination elicits neutralising antibodies in sera and cervicovaginal secretions and protects uninfected individuals from persistent anogenital infection and associated diseases caused by the vaccine-targeted HPV types. Whether immunisation can prevent oropharyngeal infection and diseases and whether neutralising antibodies represent the correlate of protection, is still unclear. Methods: We determined IgG and neutralising antibodies against low-risk HPV6 and high-risk HPV16/18 in sera and oral fluids from healthy females (n=20) before and after quadrivalent HPV-vaccination and compared the results with non-vaccinated controls. Results: HPV-vaccination induced type-specific antibodies in sera and oral fluids of the vaccinees. Importantly, the antibodies in oral fluids were capable of neutralising HPV pseudovirions in vitro, indicating protection from infection. The increased neutralising antibody levels against HPV16/18 in sera and oral fluids post-vaccination correlated significantly within an individual. Conclusions: We provide experimental proof that HPV-vaccination elicits neutralising antibodies to the vaccine-targeted types in oral fluids. Hence, immunisation may confer direct protection against type-specific HPV infection and associated diseases of the oropharyngeal tract. Measurement of antibodies in oral fluids represents a suitable tool to assess vaccine-induced protection within the mucosal milieu of the orophayrynx. PMID:26867163

  14. Magnetic Purification of Antibodies

    Science.gov (United States)

    Dhadge, Vijaykumar Laxman

    This work aimed at the development of magnetic nanoparticles for antibody purification and at the evaluation of their performance in Magnetic fishing and in a newly developed hybrid technology Magnetic Aqueous Two Phase Systems. Magnetic materials were produced by coprecipitation and solvothermal approaches. Natural polymers such as dextran, extracellular polysaccharide and gum Arabic were employed for coating of iron oxide magnetic supports. Polymer coated magnetic supports were then modified with synthetic antibody specific ligands,namely boronic acid, a triazine ligand (named 22/8) and an Ugi ligand (named A2C7I1). To optimize the efficacy of magnetic nanoparticles for antibody magnetic fishing, various solutions of pure and crude antibody solutions along with BSA as a non-specific binding protein were tested. The selectivity of magnetic nanoparticle for antibody, IgG, was found effective with boronic acid and ligand 22/8. Magnetic supports were then studied for their performance in high gradient magnetic separator for effective separation capability as well as higher volume handling capability. The magnetic materials were also supplemented to aqueous two phase systems, devising a new purification technology. For this purpose, magnetic particles modified with boronic acid were more effective. This alternative strategy reduced the time of operation,maximized separation capability (yield and purity), while reducing the amount of salt required. Boronic acid coated magnetic particles bound 170 +/- 10 mg hIgG/g MP and eluted 160 +/- 5 mg hIgG/g MP, while binding only 15 +/- 5 mg BSA/g MP. The affinity constant for the interaction between hIgG and APBA_MP was estimated as 4.9 x 105 M-1 (Ka) with a theoretical maximum capacity of 492 mg hIgG adsorbed/g MP (Qmax). APBA_MPs were also tested for antibody purification directly from CHO cell supernatants. The particles were able to bind 98% of IgG loaded and to recover 95% of pure IgG (purity greater than 98%) at extremely

  15. 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.

  16. Making Recombinant Monoclonal Antibody And Radiolabelling For Medical Purpose

    International Nuclear Information System (INIS)

    Nguyen Thi Thu; Duong Van Dong; Vo Thi Cam Hoa; Bui Van Cuong; Chu Van Khoa; Vu Bich Huong; Le Quang Huan

    2008-01-01

    Recombinant monoclonal antibody labeling with 131 I specific to tumor cell has been studied and prepared for treatment of Hodgkin lymphoma. In this study, a recombinant monoclonal antibody with two specific properties is a hybrid molecule created by coupling an antibody variable fragments with peptide melittin. The gene coding the antibody fragment has been obtained from human synthetic Fv libraries using for panning and screening on populations of lymphocytes fragmented from human blood cells with Hodgkin diseases. The gene encoding peptit melittin has been cloned from honeybee Apis cerana DNA. The gene coding recombinant monoclonal antibody has been expressed in E.coli BL21 (DE3) at 37 o C and was induced with 0.6 mM IPTG. The recombinant compound has been purified by affinity chromatography with HiTrap affinity column. The obtained recombinant monoclonal antibody has showed cytolytic activities when added to cell culture medium for LU cancer cell line with the amount of 100 - 200 mg/ml. This monoclonal antibody is labeled with 131 I using chloramine T procedure. ChT mass for the oxidation of 50 μg monoclonal antibody in 76 MBq was 10 μg. Sodium metabisulfite was used as a reducing agent. Reaction time was above 3 mins. The radiochemical purity was determined using electrophoresis and TLC methods. Radiochemical yield was > 97%. Radiochemical purity after purification was > 99%. Nuclear purity was > 99%. Stability of the label antibody was 12 days. This is the product promise potential used in the diagnostic and therapeutic of Hodgkin lymphoma. (author)

  17. Antibody neutralization of retargeted measles viruses

    Science.gov (United States)

    Lech, Patrycja J.; Pappoe, Roland; Nakamura, Takafumi; Tobin, Gregory J.; Nara, Peter L.; Russell, Stephen J.

    2014-01-01

    The measles virus (MV) vaccine lineage is a promising oncolytic but prior exposure to the measles vaccine or wild-type MV strains limits treatment utility due to the presence of anti-measles antibodies. MV entry can be redirected by displaying a polypeptide ligand on the Hemagglutinin (H) C-terminus. We hypothesized that retargeted MV would escape neutralization by monoclonal antibodies (mAbs) recognizing the H receptor-binding surface and be less susceptible to neutralization by human antisera. Using chimeric H proteins, with and without mutations that ablate MV receptor binding, we show that retargeted MVs escape mAbs that target the H receptor-binding surface by virtue of mutations that ablate infection via SLAM and CD46. However, C-terminally displayed domains do not mediate virus entry in the presence of human antibodies that bind to the underlying H domain. In conclusion, utility of retargeted oncolytic measles viruses does not extend to evasion of human serum neutralization. PMID:24725950

  18. Monoclonal antibodies based on hybridoma technology.

    Science.gov (United States)

    Yagami, Hisanori; Kato, Hiroshi; Tsumoto, Kanta; Tomita, Masahiro

    2013-03-01

    Based on the size and scope of the present global market for medicine, monoclonal antibodies (mAbs) have a very promising future, with applications for cancers through autoimmune ailments to infectious disease. Since mAbs recognize only their target antigens and not other unrelated proteins, pinpoint medical treatment is possible. Global demand is dramatically expanding. Hybridoma technology, which allows production of mAbs directed against antigens of interest is therefore privileged. However, there are some pivotal points for further development to generate therapeutic antibodies. One is selective generation of human mAbs. Employment of transgenic mice producing human antibodies would overcome this problem. Another focus is recognition sites and conformational epitopes in antigens may be just as important as linear epitopes, especially when membrane proteins such as receptors are targeted. Recognition of intact structures is of critical importance for medical purposes. In this review, we describe patent related information for therapeutic mAbs based on hybridoma technology and also discuss new advances in hybridoma technology that facilitate selective production of stereospecific mAbs.

  19. Epigenetic epidemiology: promises for public health research.

    Science.gov (United States)

    Bakulski, Kelly M; Fallin, M Daniele

    2014-04-01

    Epigenetic changes underlie developmental and age related biology. Promising epidemiologic research implicates epigenetics in disease risk and progression, and suggests epigenetic status depends on environmental risks as well as genetic predisposition. Epigenetics may represent a mechanistic link between environmental exposures, or genetics, and many common diseases, or may simply provide a quantitative biomarker for exposure or disease for areas of epidemiology currently lacking such measures. This great promise is balanced by issues related to study design, measurement tools, statistical methods, and biological interpretation that must be given careful consideration in an epidemiologic setting. This article describes the promises and challenges for epigenetic epidemiology, and suggests directions to advance this emerging area of molecular epidemiology. Copyright © 2014 Wiley Periodicals, Inc.

  20. 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

  1. Antibody Production with Synthetic Peptides.

    Science.gov (United States)

    Lee, Bao-Shiang; Huang, Jin-Sheng; Jayathilaka, Lasanthi P; Lee, Jenny; Gupta, Shalini

    2016-01-01

    Peptides (usually 10-20 amino acid residues in length) can be used as effectively as proteins in raising antibodies producing both polyclonal and monoclonal antibodies routinely with titers higher than 20,000. Peptide antigens do not function as immunogens unless they are conjugated to proteins. Production of high quality antipeptide antibodies is dependent upon peptide sequence selection, the success of peptide synthesis, peptide-carrier protein conjugation, the humoral immune response in the host animal, the adjuvant used, the peptide dose administered, the injection method, and the purification of the antibody. Peptide sequence selection is probably the most critical step in the production of antipeptide antibodies. Although the process for designing peptide antigens is not exact, several guidelines and computational B-cell epitope prediction methods can help maximize the likelihood of producing antipeptide antibodies that recognize the protein. Antibodies raised by peptides have become essential tools in life science research. Virtually all phospho-specific antibodies are now produced using phosphopeptides as antigens. Typically, 5-20 mg of peptide is enough for antipeptide antibody production. It takes 3 months to produce a polyclonal antipeptide antibody in rabbits that yields ~100 mL of serum which corresponds to ~8-10 mg of the specific antibody after affinity purification using a peptide column.

  2. Beware of Products Promising Miracle Weight Loss

    Science.gov (United States)

    ... Consumers Consumer Updates Beware of Products Promising Miracle Weight Loss Share Tweet Linkedin Pin it More sharing options ... Year’s resolution, know this: many so-called “miracle” weight loss supplements and foods (including teas and coffees) don’ ...

  3. Big data in nephrology: promises and pitfalls.

    Science.gov (United States)

    Nadkarni, Girish N; Coca, Steven G; Wyatt, Christina M

    2016-08-01

    Data from the electronic health records hold great promise for nephrology research. However, due to significant limitations, reporting guidelines have been formulated for analyses conducted using electronic health records data. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  4. 76 FR 39589 - Promise Neighborhoods Program

    Science.gov (United States)

    2011-07-06

    ... Innovation and Improvement, Department of Education. ACTION: Notice of final priorities, requirements... Dropout/Graduation Crisis Among American Indian and Alaska Native Students: Failure to Respond Places the... success of Promise Neighborhoods will require the use of both short-term and long-term goals to measure...

  5. Complexity of Propositional Proofs Under a Promise

    Czech Academy of Sciences Publication Activity Database

    Dershowitz, N.; Tzameret, Iddo

    2010-01-01

    Roč. 11, č. 3 (2010), s. 1-29 ISSN 1529-3785 Institutional research plan: CEZ:AV0Z10190503 Keywords : theory * promise problems * propositional proof complexity * random 3CNF * resolution Subject RIV: BA - General Mathematics Impact factor: 1.391, year: 2010 http://dl.acm.org/ citation .cfm?doid=1740582.1740586

  6. Complexity of Propositional Proofs Under a Promise

    Czech Academy of Sciences Publication Activity Database

    Dershowitz, N.; Tzameret, Iddo

    2010-01-01

    Roč. 11, č. 3 (2010), s. 1-29 ISSN 1529-3785 Institutional research plan: CEZ:AV0Z10190503 Keywords : theory * promise problems * propositional proof complexity * random 3CNF * resolution Subject RIV: BA - General Mathematics Impact factor: 1.391, year: 2010 http://dl.acm.org/citation.cfm?doid=1740582.1740586

  7. FcγRII-binding Centyrins mediate agonism and antibody-dependent cellular phagocytosis when fused to an anti-OX40 antibody.

    Science.gov (United States)

    Zhang, Di; Whitaker, Brian; Derebe, Mehabaw G; Chiu, Mark L

    2018-04-01

    Immunostimulatory antibodies against the tumor necrosis factor receptors (TNFR) are emerging as promising cancer immunotherapies. The agonism activity of such antibodies depends on crosslinking to Fc gamma RIIB receptor (FcγRIIB) to enable the antibody multimerization that drives TNFR activation. Previously, Fc engineering was used to enhance the binding of such antibodies to Fcγ receptors. Here, we report the identification of Centyrins as alternative scaffold proteins with binding affinities to homologous FcγRIIB and FcγRIIA, but not to other types of Fcγ receptors. One Centyrin, S29, was engineered at distinct positions of an anti-OX40 SF2 antibody to generate bispecific and tetravalent molecules named as mAbtyrins. Regardless of the position of S29 on the SF2 antibody, SF2-S29 mAbtyrins could bind FcγRIIB and FcγRIIA specifically while maintaining binding to OX40 receptors. In a NFκB reporter assay, attachment of S29 Centyrin molecules at the C-termini, but not the N-termini, resulted in SF2 antibodies with increased agonism owing to FcγRIIB crosslinking. The mAbtyrins also showed agonism in T-cell activation assays with immobilized FcγRIIB and FcγRIIA, but this activity was confined to mAbtyrins with S29 specifically at the C-termini of antibody heavy chains. Furthermore, regardless of the position of the molecule, S29 Centyrin could equip an otherwise Fc-silent antibody with antibody-dependent cellular phagocytosis activity without affecting the antibody's intrinsic antibody-dependent cell-meditated cytotoxicity and complement-dependent cytotoxicity. In summary, the appropriate adoption FcγRII-binding Centyrins as functional modules represents a novel strategy to engineer therapeutic antibodies with improved functionalities.

  8. Therapeutic antibodies as a treatment option for dengue fever.

    Science.gov (United States)

    Chan, Kuan Rong; Ong, Eugenia Z; Ooi, Eng Eong

    2013-11-01

    Dengue fever is the most prevalent mosquito-borne viral disease globally with about 100 million cases of acute dengue annually. Severe dengue infection can result in a life-threatening illness. In the absence of either a licensed vaccine or antiviral drug against dengue, therapeutic antibodies that neutralize dengue virus (DENV) may serve as an effective medical countermeasure against severe dengue. However, therapeutic antibodies would need to effectively neutralize all four DENV serotypes. It must not induce antibody-dependent enhancement of DENV infection in monocytes/macrophages through Fc gamma receptor (FcγR)-mediated phagocytosis, which is hypothesized to increase the risk of severe dengue. Here, we review the strategies and technologies that can be adopted to develop antibodies for therapeutic applications. We also discuss the mechanism of antibody neutralization in the cells targeted by DENV that express Fc gamma receptor. These studies have provided significant insight toward the use of therapeutic antibodies as a potentially promising bulwark against dengue.

  9. Antibodies from a Human Survivor Define Sites of Vulnerability for Broad Protection against Ebolaviruses.

    Science.gov (United States)

    Wec, Anna Z; Herbert, Andrew S; Murin, Charles D; Nyakatura, Elisabeth K; Abelson, Dafna M; Fels, J Maximilian; He, Shihua; James, Rebekah M; de La Vega, Marc-Antoine; Zhu, Wenjun; Bakken, Russell R; Goodwin, Eileen; Turner, Hannah L; Jangra, Rohit K; Zeitlin, Larry; Qiu, Xiangguo; Lai, Jonathan R; Walker, Laura M; Ward, Andrew B; Dye, John M; Chandran, Kartik; Bornholdt, Zachary A

    2017-05-18

    Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease. Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GP CL ) generated in host cell endosomes. Only a few somatic hypermutations are required for broad antiviral activity, and germline-approximating variants display enhanced GP CL recognition, suggesting that such antibodies could be elicited more efficiently with suitably optimized GP immunogens. Our findings inform the development of both broadly effective immunotherapeutics and vaccines against filoviruses. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Single dose of glycoengineered anti-CD19 antibody (MEDI551) disrupts experimental autoimmune encephalomyelitis by inhibiting pathogenic adaptive immune responses in the bone marrow and spinal cord while preserving peripheral regulatory mechanisms.

    Science.gov (United States)

    Chen, Ding; Blazek, Monica; Ireland, Sara; Ortega, Sterling; Kong, Xiangmei; Meeuwissen, Anouk; Stowe, Ann; Carter, Laura; Wang, Yue; Herbst, Ronald; Monson, Nancy L

    2014-11-15

    Plasma cells and the autoreactive Abs they produce are suspected to contribute to the pathogenesis of multiple sclerosis, but recent attempts to target these components of humoral immunity have failed. MEDI551, an anti-CD19 Ab that depletes mature B cells including plasma cells may offer a compelling alternative that reduces pathogenic adaptive immune responses while sparing regulatory mechanisms. Indeed, our data demonstrate that a single dose of MEDI551, given before or during ongoing experimental autoimmune encephalomyelitis, disrupts development of the disease. Leukocyte infiltration into the spinal cord is significantly reduced, as well as short-lived and long-lived autoreactive CD138(+) plasma cells in the spleen and bone marrow, respectively. In addition, potentially protective CD1d(hi)CD5(+) regulatory B cells show resistance to depletion, and myelin-specific Foxp3(+) regulatory T cells are expanded. Taken together, these results demonstrate that MEDI551 disrupts experimental autoimmune encephalomyelitis by inhibiting multiple proinflammatory components whereas preserving regulatory populations. Copyright © 2014 by The American Association of Immunologists, Inc.

  11. [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

  12. Structure-Based Design of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses to a Conserved Epitope

    Energy Technology Data Exchange (ETDEWEB)

    Pierce, Brian G.; Boucher, Elisabeth N.; Piepenbrink, Kurt H.; Ejemel, Monir; Rapp, Chelsea A.; Thomas, William D.; Sundberg, Eric J.; Weng, Zhiping; Wang, Yang; Diamond, Michael S.

    2017-08-09

    Despite recent advances in therapeutic options, hepatitis C virus (HCV) remains a severe global disease burden, and a vaccine can substantially reduce its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response; thus, an effective vaccine must target conserved, functionally important epitopes. Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412 to 423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope. This resulted in epitope-based immunogens based on a cyclic defensin protein, as well as a bivalent immunogen with two copies of the epitope on the E2 surface. We solved the X-ray structure of a cyclic immunogen in complex with the HCV1 antibody and confirmed preservation of the epitope conformation and the HCV1 interface. Mice vaccinated with our designed immunogens produced robust antibody responses to epitope I, and their serum could neutralize HCV. Notably, the cyclic designs induced greater epitope-specific responses and neutralization than the native peptide epitope. Beyond successfully designing several novel HCV immunogens, this study demonstrates the principle that neutralizing anti-HCV antibodies can be induced by epitope-based, engineered vaccines and provides the basis for further efforts in structure-based design of HCV vaccines.

    IMPORTANCEHepatitis C virus is a leading cause of liver disease and liver cancer, with approximately 3% of the world's population infected. To combat this virus, an effective vaccine would have distinct advantages over current therapeutic options, yet experimental vaccines have not been successful to date, due in part to the virus's high sequence variability leading to immune escape. In this study, we rationally designed several vaccine immunogens based on the structure of a conserved epitope that

  13. Service Users perspectives in PROMISE and research.

    Science.gov (United States)

    Rae, Sarah

    2017-09-01

    Since its inception in 2013, PROMISE (PROactive Management of Integrated Services and Environments) has been supporting service users and staff at the Cambridgeshire and Peterborough NHS Foundation Trust (CPFT) on a journey to reduce reliance on force. The author's own personal experiences led to the founding of PROMISE and illustrates how individual experiences can influence a patient to lead change. Coproduction is actively embedded in PROMISE. Patients have been meaningfully involved because they are innovators and problem solvers who bring an alternative viewpoint by the very nature of their condition. A patient is more than just a person who needs to be 'fixed' they are individuals with untapped skills and added insight. There have been 2 separate Patient Advisory Groups (PAGs) since the project was first established. The first Patient Advisory Group was recruited to work with the PROMISE researchers on a study which used a participatory qualitative approach. Drawing on their lived experience and different perspectives the PAG was instrumental in shaping the qualitative study, including the research questions. Their active involvement helped to ensure that that the study was sensitively designed, methodologically robust and ethically sound. The 2 nd PAG was formed in 2016 to give the project an overall steer. Patients in this group contributed to the work on the 'No' Audit and reviewed several CPFT policies such as the Seclusion and Segregation policy which has impacted on frontline practice. They also made a significant contribution to the study design for a funding application that was submitted by the PROMISE team to the National Institute for Health Research (NIHR). Both PAGs were supported by funding from East of England Collaboration for Leadership in Applied Health Research and Care (CLAHRC EoE) and were influential in different ways. An evaluation of the 2 nd PAG which was conducted in June 2017 showed very high satisfaction levels. The free text

  14. A rational approach to enhancing antibody Fc homodimer formation for robust production of antibody mixture in a single cell line.

    Science.gov (United States)

    Yu, Jie; Wang, Xiaoxiao; Xu, Tao; Jin, Qiuheng; Duan, Jinyuan; Wu, Jie; Wu, Haiyan; Xu, Ting; Ye, Sheng

    2017-10-27

    Combinations of different antibodies have been shown to be more effective for managing certain diseases than monotherapy. Co-expression of the antibody mixture in a single cell line is key to reducing complexity during antibody development and manufacturing. However, co-transfection of multiple light and heavy chains into cells often leads to production of mismatched, heterodimeric by-products that are inactive, making the development of co-expression systems that robustly and efficiently produce highly active antibody mixtures a high priority. In this study, we modified the CH3 domain interface of the antibody fragment crystallizable (Fc) region by changing several charge pairs to create electrostatic interactions favoring Fc homodimer formation and disfavoring Fc heterodimer formation. When co-expressed, these modified antibodies with altered charge polarity across the Fc dimer interface preferentially formed homodimers that fully preserved the functions of each component, rather than inactive heterodimers whose formation was reduced because of rationally designed repulsive interactions. We designed eight different combinations and experimentally screened the best one, which enabled us to produce a binary antibody mixture against the EGF receptor with a minimal heterodimer contaminant. We further determined the crystal structure of a triple-mutated Fc variant in the best combination, and we elucidated the molecular interactions favoring Fc homodimer over heterodimer formation, which provided a structural basis for further optimization. The approach presented here demonstrates the feasibility of rational antibody modification for efficient and consistent production of monoclonal antibody mixtures in a single cell line and thus broadens our options for manufacturing more effective antibody-based therapeutic agents. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. 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

  16. The effects of tether placement on antibody stability on surfaces

    Science.gov (United States)

    Grawe, Rebecca W.; Knotts, Thomas A.

    2017-06-01

    Despite their potential benefits, antibody microarrays have fallen short of performing reliably and have not found widespread use outside of the research setting. Experimental techniques have been unable to determine what is occurring on the surface of an atomic level, so molecular simulation has emerged as the primary method of investigating protein/surface interactions. Simulations of small proteins have indicated that the stability of the protein is a function of the residue on the protein where a tether is placed. The purpose of this research is to see whether these findings also apply to antibodies, with their greater size and complexity. To determine this, 24 tethering locations were selected on the antibody Protein Data Bank (PDB) ID: 1IGT. Replica exchange simulations were run on two different surfaces, one hydrophobic and one hydrophilic, to determine the degree to which these tethering sites stabilize or destabilize the antibody. Results showed that antibodies tethered to hydrophobic surfaces were in general less stable than antibodies tethered to hydrophilic surfaces. Moreover, the stability of the antibody was a function of the tether location on hydrophobic surfaces but not hydrophilic surfaces.

  17. The deepwater Gulf of Mexico : promises delivered?

    International Nuclear Information System (INIS)

    Pickering, D.R.

    1999-01-01

    A summary review of deepwater Gulf of Mexico (GOM) oil production was presented for the years 1989 to 1998. Trends and prospects in deepwater GOM production and leasing were assessed. Promises and forecasts made in the early 1990s were compared with what actually happened since then. Forecasts in the early 1990s promised deeper, faster and cheaper developments in the deepwater Gulf. Results of the comparison showed that the prognosticators were correct on all three counts. Regarding the future of the Gulf, one can be justified in being optimistic in so far as more experience, robust economics, more and cheaper rigs can be taken as reliable indicators of optimism. In contrast, there are certain negatives to consider, such as low commodity prices, budget constraints, lease expirations, technical challenges and increased competition. . 12 figs

  18. Promising Products for Printing and Publishing Market

    Directory of Open Access Journals (Sweden)

    Renata Činčikaitė

    2011-04-01

    Full Text Available The article surveys printing and publishing market and its strong and weak aspects. The concept of a new product is described as well as its lifetime and the necessity of its introduction to the market. The enterprise X operating on the market is analyzed, its strong and weak characteristics are presented. The segmentation of the company consumers is performed. On the basis of the performed analysis the potential promising company products are defined.Article in Lithuanian

  19. Antibody-protein A conjugated quantum dots for multiplexed imaging of surface receptors in living cells.

    Science.gov (United States)

    Jin, Takashi; Tiwari, Dhermendra K; Tanaka, Shin-Ichi; Inouye, Yasushi; Yoshizawa, Keiko; Watanabe, Tomonobu M

    2010-11-01

    To use quantum dots (QDs) as fluorescent probes for receptor imaging, QD surface should be modified with biomolecules such as antibodies, peptides, carbohydrates, and small-molecule ligands for receptors. Among these QDs, antibody conjugated QDs are the most promising fluorescent probes. There are many kinds of coupling reactions that can be used for preparing antibody conjugated QDs. Most of the antibody coupling reactions, however, are non-selective and time-consuming. In this paper, we report a facile method for preparing antibody conjugated QDs for surface receptor imaging. We used ProteinA as an adaptor protein for binding of antibody to QDs. By using ProteinA conjugated QDs, various types of antibodies are easily attached to the surface of the QDs via non-covalent binding between the F(c) (fragment crystallization) region of antibody and ProteinA. To show the utility of ProteinA conjugated QDs, HER2 (anti-human epidermal growth factor receptor 2) in KPL-4 human breast cancer cells were stained by using anti-HER2 antibody conjugated ProteinA-QDs. In addition, multiplexed imaging of HER2 and CXCR4 (chemokine receptor) in the KPL-4 cells was performed. The result showed that CXCR4 receptors coexist with HER2 receptors in the membrane surface of KPL-4 cells. ProteinA mediated antibody conjugation to QDs is very useful to prepare fluorescent probes for multiplexed imaging of surface receptors in living cells.

  20. The future of monoclonal antibody technology

    OpenAIRE

    Zider, Alexander; Drakeman, Donald L

    2010-01-01

    With the rapid growth of monoclonal antibody-based products, new technologies have emerged for creating modified forms of antibodies, including fragments, conjugates and multi-specific antibodies. We created a database of 450 therapeutic antibodies in development to determine which technologies and indications will constitute the “next generation” of antibody products. We conclude that the antibodies of the future will closely resemble the antibodies that have already been approved for commer...

  1. Detection of anti-Toxoplasma gondii antibodies in experimentally and naturally infected non-human primates by Indirect Fluorescence Assay (IFA and indirect ELISA Detecção de anticorpos anti-Toxoplasma gondii por meio das técnicas de Imunofluorescência Indireta e ELISA Indireto em primatas experimentalmente e naturalmente infectados

    Directory of Open Access Journals (Sweden)

    Andréa Bouer

    2010-03-01

    Full Text Available The Indirect Fluorescence Assay (IFA and the indirect ELISA were comparatively used to detect IgG and IgM antibodies for Toxoplasma gondii in experimentally and naturally infected primates. In the experimentally infected group, antibodies of diagnostic value were detected at day 9 post-infection (PI with the IFA (IgG and IgM and with IgG-ELISA. IgM-ELISA detected antibodies for T. gondii starting at day 3 PI until the end of the experiment (102 days PI. Of the 209 naturally infected sera tested, from many zoos of State of Sao Paulo, 64.59 and 67.94% were positive in the IgG-IFA test and IgG-ELISA respectively. IgM-ELISA test detected seropositivity in 52.63% of the sera although IgM-IFA test detected it in only in 0.96% of the samples. The differential toxoplasmosis diagnosis was accomplished with Neospora caninum by IFA, observing 61 (29.2% seropositive animals for this parasite and 149 (70.8% negative. Sixty animals were positive for both T. gondii and N. caninum. Pneumonia, splenomegaly, and intestinal ulcers were macroscopically observed. Unremarkable interstitial pneumonia, enteritis, colitis, splenitis, and glomerulitis were microscopically observed. The immunohistochemical stain could not detect the presence of T. gondii in the tissues of the animals infected experimentally.Detectou-se anticorpos das classes IgG e IgM anti-Toxoplasma gondii em primatas experimentalmente e naturalmente infectados, utilizando-se como técnicas comparativas a RIFI e o ELISA-teste. No grupo dos primatas experimentalmente infectados, anticorpos de valor diagnóstico foram detectados a partir do 9º dia de infecção tanto na RIFI (IgG e IgM como no ELISA-IgG. O ELISA IgM detectou anticorpos a partir do 3º dia de infecção até o final do experimento (102 dias pós-infecção. Dos 209 soros dos primatas naturalmente infectados, de diversos zoológicos do Estado de São Paulo, 64,59 e 67,94% mostraram-se positivos na RIFI-IgG e no ELISA-IgG, respectivamente. O

  2. Tabhu: tools for antibody humanization

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...... 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...... of the humanization experiment protocol....

  3. Cancer Imaging and Therapy with Bispecific Antibody Pretargeting

    OpenAIRE

    Goldenberg, David M.; Chatal, Jean-Francois; Barbet, Jacques; Boerman, Otto; Sharkey, Robert M.

    2007-01-01

    This article reviews recent preclinical and clinical advances in the use of pretargeting methods for the radioimmunodetection and radioimmunotherapy of cancer. Whereas directly-labeled antibodies, fragments, and subfragments (minibodies and other constructs) have shown promise in both imaging and therapy applications over the past 25 years, their clinical adoption has not fulfilled the original expectations due to either poor image resolution and contrast in scanning or insufficient radiation...

  4. Lepromatous leprosy patients produce antibodies that recognise non-bilayer lipid arrangements containing mycolic acids

    Directory of Open Access Journals (Sweden)

    Isabel Baeza

    2012-12-01

    Full Text Available Non-bilayer phospholipid arrangements are three-dimensional structures that form when anionic phospholipids with an intermediate structure of the tubular hexagonal phase II are present in a bilayer of lipids. Antibodies that recognise these arrangements have been described in patients with antiphospholipid syndrome and/or systemic lupus erythematosus and in those with preeclampsia; these antibodies have also been documented in an experimental murine model of lupus, in which they are associated with immunopathology. Here, we demonstrate the presence of antibodies against non-bilayer phospholipid arrangements containing mycolic acids in the sera of lepromatous leprosy (LL patients, but not those of healthy volunteers. The presence of antibodies that recognise these non-bilayer lipid arrangements may contribute to the hypergammaglobulinaemia observed in LL patients. We also found IgM and IgG anti-cardiolipin antibodies in 77% of the patients. This positive correlation between the anti-mycolic-non-bilayer arrangements and anti-cardiolipin antibodies suggests that both types of antibodies are produced by a common mechanism, as was demonstrated in the experimental murine model of lupus, in which there was a correlation between the anti-non-bilayer phospholipid arrangements and anti-cardiolipin antibodies. Antibodies to non-bilayer lipid arrangements may represent a previously unrecognised pathogenic mechanism in LL and the detection of these antibodies may be a tool for the early diagnosis of LL patients.

  5. Theranostics Using Antibodies and Antibody-Related Therapeutics

    NARCIS (Netherlands)

    Moek, Kirsten L; Giesen, Danique; Kok, Iris C; de Groot, Derk Jan A; Jalving, Mathilde; Fehrmann, Rudolf S N; Lub-de Hooge, Marjolijn N; Brouwers, Adrienne H; de Vries, Elisabeth G E

    In theranostics, radiolabeled compounds are used to determine a treatment strategy by combining therapeutics and diagnostics in the same agent. Monoclonal antibodies (mAbs) and antibody-related therapeutics represent a rapidly expanding group of cancer medicines. Theranostic approaches using these

  6. Comprehensive evaluation and optimization of amplicon library preparation methods for high-throughput antibody sequencing.

    Science.gov (United States)

    Menzel, Ulrike; Greiff, Victor; Khan, Tarik A; Haessler, Ulrike; Hellmann, Ina; Friedensohn, Simon; Cook, Skylar C; Pogson, Mark; Reddy, Sai T

    2014-01-01

    High-throughput sequencing (HTS) of antibody repertoire libraries has become a powerful tool in the field of systems immunology. However, numerous sources of bias in HTS workflows may affect the obtained antibody repertoire data. A crucial step in antibody library preparation is the addition of short platform-specific nucleotide adapter sequences. As of yet, the impact of the method of adapter addition on experimental library preparation and the resulting antibody repertoire HTS datasets has not been thoroughly investigated. Therefore, we compared three standard library preparation methods by performing Illumina HTS on antibody variable heavy genes from murine antibody-secreting cells. Clonal overlap and rank statistics demonstrated that the investigated methods produced equivalent HTS datasets. PCR-based methods were experimentally superior to ligation with respect to speed, efficiency, and practicality. Finally, using a two-step PCR based method we established a protocol for antibody repertoire library generation, beginning from inputs as low as 1 ng of total RNA. In summary, this study represents a major advance towards a standardized experimental framework for antibody HTS, thus opening up the potential for systems-based, cross-experiment meta-analyses of antibody repertoires.

  7. Diversity Against Adversity: How Adaptive Immune System Evolves Potent Antibodies

    Science.gov (United States)

    Heo, Muyoung; Zeldovich, Konstantin B.; Shakhnovich, Eugene I.

    2011-07-01

    Adaptive immunity is an amazing mechanism, whereby new protein functions—affinity of antibodies (Immunoglobulins) to new antigens—evolve through mutation and selection in a matter of a few days. Despite numerous experimental studies, the fundamental physical principles underlying immune response are still poorly understood. In considerable departure from past approaches, here, we propose a microscopic multiscale model of adaptive immune response, which consists of three essential players: The host cells, viruses, and B-cells in Germinal Centers (GC). Each moiety carries a genome, which encodes proteins whose stability and interactions are determined from their sequences using laws of Statistical Mechanics, providing an exact relationship between genomic sequences and strength of interactions between pathogens and antibodies and antibodies and host proteins (autoimmunity). We find that evolution of potent antibodies (the process known as Affinity Maturation (AM)) is a delicate balancing act, which has to reconcile the conflicting requirements of protein stability, lack of autoimmunity, and high affinity of antibodies to incoming antigens. This becomes possible only when antibody producing B cells elevate their mutation rates (process known as Somatic Hypermutation (SHM)) to fall into a certain range—not too low to find potency increasing mutations but not too high to destroy stable Immunoglobulins and/or already achieved affinity. Potent antibodies develop through clonal expansion of initial B cells expressing marginally potent antibodies followed by their subsequent affinity maturation through mutation and selection. As a result, in each GC the population of mature potent Immunoglobulins is monoclonal being ancestors of a single cell from initial (germline) pool. We developed a simple analytical theory, which provides further rationale to our findings. The model and theory reveal the molecular factors that determine the efficiency of affinity maturation

  8. Analysis of promising sustainable renovation concepts

    DEFF Research Database (Denmark)

    Vanhoutteghem, Lies; Tommerup, Henrik M.; Svendsen, Svend

    This report focuses on analyses of the most promising existing sustainable renovation concepts, i.e. full-service concepts and technical concepts, for single-family houses. As a basis for the analyses a detailed building stock analysis was carried out. Furthermore, as a basis a general working...... and contractors and the idea is to help the homeowner with design and decision making process. The building stock analysis shows that detached single-family houses account for large share of the total number of dwellings in all Nordic countries. Final energy use for space heating and hot water is in the range...

  9. Natural antibodies in normal human serum inhibit Staphylococcus aureus capsular polysaccharide vaccine efficacy.

    Science.gov (United States)

    Skurnik, David; Kropec, Andrea; Roux, Damien; Theilacker, Christian; Huebner, Johannes; Pier, Gerald B

    2012-11-01

    Vaccines against Streptococcus pneumoniae, Neisseria meningitidis, and Hemophilus influenzae type b induce functional opsonic or bactericidal antibodies to surface capsular polysaccharides (CP). Targeting the comparable Staphylococcus aureus CP seems logical, but to date such efforts have failed in human trials. Studies using immunization-induced animal antibodies have documented interference in opsonic and protective activities of antibodies to CP by antibodies to another S. aureus cell surface polysaccharide, poly-N-acetyl glucosamine (PNAG). Here we evaluated whether natural antibody to PNAG in normal human serum (NHS) had a similar deleterious effect. Functional and/or protective activities of antibody to S. aureus CP and PNAG antigens in patients with bacteremia, in mice immunized with combinations of CP and PNAG conjugate vaccines, and in serum samples of healthy subjects with natural antibody to PNAG, to which immunization-induced animal antibodies to CP antigens were added, were evaluated. Antibodies to PNAG and CP that mutually interfered with opsonic killing of S. aureus were detected in 9 of 15 bacteremic patients. Active immunization of mice with combinations of PNAG and CP conjugate antigens always induced antibodies that interfered with each other's functional activity. Non-opsonic natural antibodies to PNAG found in NHS interfered with the functional and protective activities of immunization-induced antibody to CP antigens during experimental infection with S. aureus. Both immunization-induced animal antibodies and natural antibodies to PNAG in NHS interfere with the protective activities of immunization-induced antibody to S. aureus CP5 and CP8 antigens, representing potential barriers to successful use of CP-specific vaccines.

  10. 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.

  11. Antibodies and Plasmodium falciparum merozoites

    NARCIS (Netherlands)

    Ramasamy, R; Ramasamy, M; Yasawardena, S

    There is considerable interest in using merozoite proteins in a vaccine against falciparum malaria. Observations that antibodies to merozoite surface proteins block invasion are a basis for optimism. This article draws attention to important and varied aspects of how antibodies to Plasmodium

  12. Antiphospholipid antibodies: standardization and testing.

    Science.gov (United States)

    Riley, R S; Friedline, J; Rogers, J S

    1997-09-01

    A phenomenon originally scorned as a laboratory nuisance has turned out to be an important cause of thromboembolism, fetal death, and other forms of human disease. Investigations of this inaptly named "lupus anticoagulant" has led to the discovery of at least two distinct types of autoimmune antibodies. In spite of recent discoveries regarding the pathophysiology of these antibodies, their clinical significance is still controversial.

  13. Educational paper: Primary antibody deficiencies

    NARCIS (Netherlands)

    G.J.A. Driessen (Gertjan); M. van der Burg (Mirjam)

    2011-01-01

    textabstractPrimary antibody deficiencies (PADs) are the most common primary immunodeficiencies and are characterized by a defect in the production of normal amounts of antigen-specific antibodies. PADs represent a heterogeneous spectrum of conditions, ranging from often asymptomatic selective IgA

  14. Promising strategies for the prevention of dementia.

    Science.gov (United States)

    Middleton, Laura E; Yaffe, Kristine

    2009-10-01

    The incidence and prevalence of dementia are expected to increase several-fold in the coming decades. Given that the current pharmaceutical treatment of dementia can only modestly improve symptoms, risk factor modification remains the cornerstone for dementia prevention. Some of the most promising strategies for the prevention of dementia include vascular risk factor control, cognitive activity, physical activity, social engagement, diet, and recognition of depression. In observational studies, vascular risk factors-including diabetes, hypertension, dyslipidemia, and obesity-are fairly consistently associated with increased risk of dementia. In addition, people with depression are at high risk for cognitive impairment. Population studies have reported that intake of antioxidants or polyunsaturated fatty acids may be associated with a reduced incidence of dementia, and it has been reported that people who are cognitively, socially, and physically active have a reduced risk of cognitive impairment. However, results from randomized trials of risk factor modification have been mixed. Most promising, interventions of cognitive and physical activity improve cognitive performance and slow cognitive decline. Future studies should continue to examine the implication of risk factor modification in controlled trials, with particular focus on whether several simultaneous interventions may have additive or multiplicative effects.

  15. Microarray technology: a promising tool in nutrigenomics.

    Science.gov (United States)

    Masotti, Andrea; Da Sacco, Letizia; Bottazzo, Gian Franco; Alisi, Anna

    2010-08-01

    Microarray technology is a powerful tool for the global evaluation of gene expression profiles in tissues and for understanding many of the factors controlling the regulation of gene transcription. This technique not only provides a considerable amount of information on markers and predictive factors that may potentially characterize a specific clinical picture, but also promises new applications for therapy. One of the most recent applications of microarrays concerns nutritional genomics. Nutritional genomics, known as nutrigenomics, aims to identify and understand mechanisms of molecular interaction between nutrients and/or other dietary bioactive compounds and the genome. Actually, many nutrigenomic studies utilize new approaches such as microarrays, genomics, and bioinformatics to understand how nutrients influence gene expression. The coupling of these new technologies with nutrigenomics promises to lead to improvements in diet and health. In fact, it may provide new information which can be used to ameliorate dietary regimens and to discover novel natural agents for the treatment of important diseases such as diabetes and cancer. This critical review gives an overview of the clinical relevance of a nutritional approach to several important diseases, and proposes the use of microarray for nutrigenomic studies.

  16. Promises in intelligent plant control systems

    International Nuclear Information System (INIS)

    Otaduy, P.J.

    1987-01-01

    The control system is the brain of a power plant. The traditional goal of control systems has been productivity. However, in nuclear power plants the potential for disaster requires safety to be the dominant concern, and the worldwide political climate demands trustworthiness for nuclear power plants. To keep nuclear generation as a viable option for power in the future, trust is the essential critical goal which encompasses all others. In most of today's nuclear plants the control system is a hybrid of analog, digital, and human components that focuses on productivity and operates under the protective umbrella of an independent engineered safety system. Operation of the plant is complex, and frequent challenges to the safety system occur which impact on their trustworthiness. Advances in nuclear reactor design, computer sciences, and control theory, and in related technological areas such as electronics and communications as well as in data storage, retrieval, display, and analysis have opened a promise for control systems with more acceptable human brain-like capabilities to pursue the required goals. This paper elaborates on the promise of futuristic nuclear power plants with intelligent control systems and addresses design requirements and implementation approaches

  17. DARPins: a true alternative to antibodies.

    Science.gov (United States)

    Stumpp, Michael T; Amstutz, Patrick

    2007-03-01

    Designed ankyrin repeat proteins (DARPins) are a promising class of non-immunoglobulin proteins that can offer advantages over antibodies for target binding in drug discovery and drug development. DARPins have been successfully used, for example, for the inhibition of kinases, proteases and drug-exporting membrane proteins. DARPins specifically targeting the cancer marker HER2 have also been generated and were shown to function in both in vitro diagnostics and in vivo tumor targeting. DARPins are ideally suited for in vivo imaging or delivery of toxins or other therapeutic payloads because of their favorable molecular properties, including small size and high stability. The low-cost production in bacteria and the rapid generation of many target-specific DARPins make the DARPin approach useful for drug discovery. Additionally, DARPins can be easily generated in multispecific formats, offering the potential to target an effector DARPin to a specific organ or to target multiple receptors with one molecule composed of several DARPins.

  18. Molecular advances in pretargeting radioimunotherapy with bispecific antibodies.

    Science.gov (United States)

    Chang, Chien-Hsing; Sharkey, Robert M; Rossi, Edmund A; Karacay, Habibe; McBride, William; Hansen, Hans J; Chatal, Jean-François; Barbet, Jacques; Goldenberg, David M

    2002-05-01

    The use of antibodies against tumor-associated cell surface antigens for the targeted delivery of radionuclides was introduced >20 years ago. Although encouraging results have been achieved with radiolabeled antibodies in the management of hematopoietic malignancies, there remains a need for successfully treating solid tumors with this modality. One promising approach involving pretargeted delivery of radionuclides has been shown to be capable of significantly increasing the radioactive uptake in tumor relative to normal organs, thereby potentially improving the efficacy of both detection and therapy of cancer. Uncoupling of the radionuclide from the tumor-targeting antibody allows the relatively slow process of antibody localization and clearance to occur before a very rapid and highly specific delivery of the radioactive payload carried on a small molecule, such as a peptide. This minireview discusses the various strategies and advancements made since the concept of pretargeting was proposed in the mid-1980s, with emphasis on those comprising bispecific antibodies for cancer therapy. Critical aspects of these pretargeting systems for achieving higher tumor:nontumor ratios are considered. In addition, both preclinical and clinical results obtained from a pretargeting method known as the Affinity Enhancement System are presented. Future directions of pretargeting technology are also suggested.

  19. [Antibody induction after intrauterine interventions].

    Science.gov (United States)

    Hoch, J; Giers, G; Bald, R; Hansmann, M; Hanfland, P

    1993-06-01

    Immunohematologic and clinical data, i.e., antibody profile, location of the placenta, mode of cordocentesis, obtained from 48 pregnant patients with irregular erythrocyte antibodies during the last 2 years have been retrospectively evaluated. All fetuses of the patients received intrauterine transfusions for the treatment of fetal erythroblastosis. In 16 (33%) patients (group I) a secondarily induced antibody was detected after the onset of intrauterine transfusion therapy. 32 (67%) patients (group II) did not further develop new antibody specificities. Group I exhibited a significantly different distribution in the location of the placenta (p pregnant women. In group I a 5-fold higher rate of anterior than posterior placenta location was found. The mode of cordocentesis differed significantly (p antibodies by invasive intrauterine interventions in our patients depended indirectly on the location of the placenta and directly on the mode of the puncture (trans- vs. paraplacental access).

  20. Serum antibody response to human and bovine IRBP in uveitis

    NARCIS (Netherlands)

    Hoekzema, R.; Hwan, S. B.; Rothova, A.; van Haren, M. A.; Donoso, L. A.; Kijlstra, A.

    1990-01-01

    Interphotoreceptor retinoid binding protein (IRBP) is a 136,000 molecular weight photoreceptor cell protein capable of inducing an experimental autoimmune uveitis (EAU) in susceptible animal strains. The occurrence of serum antibodies against human (Hu) or bovine (Bo) IRBP was investigated in

  1. Animal models of antineutrophil cytoplasm antibody-associated vasculitis.

    LENUS (Irish Health Repository)

    Salama, Alan D

    2012-01-01

    To provide an update on the experimental models that have been developed recapitulating clinical antineutrophil cytoplasm antibody (ANCA) associated vasculitis. The application of the models in the study of pathogenesis, and the therapeutic implications of this, are covered in the article by van Timmeren and Heeringa in this issue.

  2. Development of Antibody Therapeutics against Flaviviruses

    Science.gov (United States)

    Sun, Haiyan; Chen, Qiang; Lai, Huafang

    2017-01-01

    Recent outbreaks of Zika virus (ZIKV) highlight the urgent need to develop efficacious interventions against flaviviruses, many of which cause devastating epidemics around the world. Monoclonal antibodies (mAb) have been at the forefront of treatment for cancer and a wide array of other diseases due to their specificity and potency. While mammalian cell-produced mAbs have shown promise as therapeutic candidates against several flaviviruses, their eventual approval for human application still faces several challenges including their potential risk of predisposing treated patients to more severe secondary infection by a heterologous flavivirus through antibody-dependent enhancement (ADE). The high cost associated with mAb production in mammalian cell cultures also poses a challenge for the feasible application of these drugs to the developing world where the majority of flavivirus infection occurs. Here, we review the current therapeutic mAb candidates against various flaviviruses including West Nile (WNV), Dengue virus (DENV), and ZIKV. The progress of using plants for developing safer and more economical mAb therapeutics against flaviviruses is discussed within the context of their expression, characterization, downstream processing, neutralization, and in vivo efficacy. The progress of using plant glycoengineering to address ADE, the major impediment of flavivirus therapeutic development, is highlighted. These advancements suggest that plant-based systems are excellent alternatives for addressing the remaining challenges of mAb therapeutic development against flavivirus and may facilitate the eventual commercialization of these drug candidates. PMID:29295568

  3. Kinetics of intralymphatically delivered monoclonal antibodies

    International Nuclear Information System (INIS)

    Wahl, R.L.; Geatti, O.; Liebert, M.; Beers, B.; Jackson, G.; Laino, L.; Kronberg, S.; Wilson, B.S.; Beierwaltes, W.H.

    1985-01-01

    Radiolabeled monoclonal antibody (MoAb) administration subcutaneously (sq), so that preferential uptake is to the lymphatics, holds significant promise for the detection of lymph node metastases. Only limited information is available about clearance rates of intralymphatically administered MoAbs. I-131 labeled intact IgG (225.28S), F(ab's)2 (225.28S) or IgM (FT162) were administered sq to anesthetized Balb/C mice. Eight mice were studied with each MoAb, 4 with a foot-pad injection, 4 with an anterior abdominal injection. Gamma camera images were collected into a computer, over the first 6 hrs after injection with the animals anesthetized and immobile. Animals were then allowed to move about freely. Additional images were then acquired out to 48 hrs. Regions of interest wre selected over the injection site and the kinetics of antibody egress determined. Clearance rates from local sq injection sites are influenced by motion and somewhat by location. The class and fragment status of the MoAb appear relatively less important in determining clearance rates from sq injections than they are in determining whole-body clearance after iv injections. Additional studies using Fab fragments and additional monoclonals will be useful in extending these observations

  4. Modulating antibody pharmacokinetics using hydrophilic polymers.

    Science.gov (United States)

    Chen, Chen; Constantinou, Antony; Deonarain, Mahendra

    2011-09-01

    The use of hydrophilic polymers as a substitute for the Fc-domain in immuno- or non-immuno-based binding proteins is accelerating. Chemical PEGylation has led the way and is still the most advanced and clinically-approved approach. Hydrophilic polymers act by maintaining a flexible conformation and hydrogen bonding to a network of water molecules to acquire a larger hydrodynamic volume and apparent mass than their actual molecular mass suggest. The benefits are increased blood half-life and bioavailability, stability and reduced immunogenicity. In the case of PEG, there is also evidence of enhanced targeting and reduced side effects, but drawbacks include the fact that PEG is non-biodegradable. This report reviews the state of the art for antibody PEGylation in terms of approaches and effects. Additionally, non-biological (such as N-(2-hydroxypropyl)methacrylamide) and potentially superior biological alternatives (such as polysialylation) are described, ending with recombinant approaches (such as hydrophilic peptides and glyco-engineering), which promise to circumvent the need for chemical modification altogether. The emergence of many small, antibody fragment-like mimics will drive the need for such technologies, and PEGylation is still the choice polymer due to its established use and track record. However, there will be a place for many alternative technologies if they can match the pharmacokinetics of PEG-conjugates and bring addition beneficial features such as easier production.

  5. Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection.

    Directory of Open Access Journals (Sweden)

    Rami Sommerstein

    2015-11-01

    Full Text Available Arenaviruses such as Lassa virus (LASV can cause severe hemorrhagic fever in humans. As a major impediment to vaccine development, delayed and weak neutralizing antibody (nAb responses represent a unifying characteristic of both natural infection and all vaccine candidates tested to date. To investigate the mechanisms underlying arenavirus nAb evasion we engineered several arenavirus envelope-chimeric viruses and glycan-deficient variants thereof. We performed neutralization tests with sera from experimentally infected mice and from LASV-convalescent human patients. NAb response kinetics in mice correlated inversely with the N-linked glycan density in the arenavirus envelope protein's globular head. Additionally and most intriguingly, infection with fully glycosylated viruses elicited antibodies, which neutralized predominantly their glycan-deficient variants, both in mice and humans. Binding studies with monoclonal antibodies indicated that envelope glycans reduced nAb on-rate, occupancy and thereby counteracted virus neutralization. In infected mice, the envelope glycan shield promoted protracted viral infection by preventing its timely elimination by the ensuing antibody response. Thus, arenavirus envelope glycosylation impairs the protective efficacy rather than the induction of nAbs, and thereby prevents efficient antibody-mediated virus control. This immune evasion mechanism imposes limitations on antibody-based vaccination and convalescent serum therapy.

  6. Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection

    Science.gov (United States)

    Malinge, Pauline; Magistrelli, Giovanni; Fischer, Nicolas; Sahin, Mehmet; Bergthaler, Andreas; Igonet, Sebastien; ter Meulen, Jan; Rigo, Dorothée; Meda, Paolo; Rabah, Nadia; Coutard, Bruno; Bowden, Thomas A.; Lambert, Paul-Henri; Siegrist, Claire-Anne; Pinschewer, Daniel D.

    2015-01-01

    Arenaviruses such as Lassa virus (LASV) can cause severe hemorrhagic fever in humans. As a major impediment to vaccine development, delayed and weak neutralizing antibody (nAb) responses represent a unifying characteristic of both natural infection and all vaccine candidates tested to date. To investigate the mechanisms underlying arenavirus nAb evasion we engineered several arenavirus envelope-chimeric viruses and glycan-deficient variants thereof. We performed neutralization tests with sera from experimentally infected mice and from LASV-convalescent human patients. NAb response kinetics in mice correlated inversely with the N-linked glycan density in the arenavirus envelope protein’s globular head. Additionally and most intriguingly, infection with fully glycosylated viruses elicited antibodies, which neutralized predominantly their glycan-deficient variants, both in mice and humans. Binding studies with monoclonal antibodies indicated that envelope glycans reduced nAb on-rate, occupancy and thereby counteracted virus neutralization. In infected mice, the envelope glycan shield promoted protracted viral infection by preventing its timely elimination by the ensuing antibody response. Thus, arenavirus envelope glycosylation impairs the protective efficacy rather than the induction of nAbs, and thereby prevents efficient antibody-mediated virus control. This immune evasion mechanism imposes limitations on antibody-based vaccination and convalescent serum therapy. PMID:26587982

  7. Cobalt Derivatives as Promising Therapeutic Agents

    Science.gov (United States)

    Heffern, Marie C.; Yamamoto, Natsuho; Holbrook, Robert J.; Eckermann, Amanda L.; Meade, Thomas J.

    2013-01-01

    Inorganic complexes are versatile platforms for the development of potent and selective pharmaceutical agents. Cobalt possesses a diverse array of properties that can be manipulated to yield promising drug candidates. Investigations into the mechanism of cobalt therapeutic agents can provide valuable insight into the physicochemical properties that can be harnessed for drug development. This review presents examples of bioactive cobalt complexes with special attention to their mechanisms of action. Specifically, cobalt complexes that elicit biological effects through protein inhibition, modification of drug activity, and bioreductive activation are discussed. Insights gained from these examples reveal features of cobalt that can be rationally tuned to produce therapeutics with high specificity and improved efficacy for the biomolecule or pathway of interest. PMID:23270779

  8. The promise and paradox of cultural competence.

    Science.gov (United States)

    Hester, Rebecca J

    2012-12-01

    Cultural competence has become a ubiquitous and unquestioned aspect of professional formation in medicine. It has been linked to efforts to eliminate race-based health disparities and to train more compassionate and sensitive providers. In this article, I question whether the field of cultural competence lives up to its promise. I argue that it does not because it fails to grapple with the ways that race and racism work in U.S. society today. Unless we change our theoretical apparatus for dealing with diversity to one that more critically engages with the complexities of race, I suggest that unequal treatment and entrenched health disparities will remain. If the field of cultural competence incorporates the lessons of critical race scholarship, however, it would not only need to transform its theoretical foundation, it would also need to change its name.

  9. Underexploited tropical plants with promising economic value

    Energy Technology Data Exchange (ETDEWEB)

    1975-01-01

    The apparent advantages of staple plants over the minor tropical plants often result only from the disproportionate research attention they have been given. A world-wide inquiry resulted in a list of 400 promising but neglected species. The 36 most important species are described in compact monographs and concern cereals (Echinochloa turnerana, grain amaranths, quinua and Zosterea mazina), roots and tubers (Arrachacha, cocoyams and taro), vegetables (chaya, hearts of palms, wax gourd, winged bean), fruits (durian, mangosteen, naranjilla, pejibaye, pummelo, soursop, uvilla), oilseeds (babassu palm, buffalo gourd, Caryocar species, Hessenia polycarpa and jojoba), forage (Acacia albida, Brosimum alicastrum Cassia sturtii, saltbushes and tamarugo) and other crops (buriti palm, Calathea lutea, candelilla, guar, guayule, Paspalum vaginatum, ramie and Spirulina).

  10. Cyanobacteria: Promising biocatalysts for sustainable chemical production.

    Science.gov (United States)

    Knoot, Cory J; Ungerer, Justin; Wangikar, Pramod P; Pakrasi, Himadri B

    2018-04-06

    Cyanobacteria are photosynthetic prokaryotes showing great promise as biocatalysts for the direct conversion of CO 2 into fuels, chemicals, and other value-added products. Introduction of just a few heterologous genes can endow cyanobacteria with the ability to transform specific central metabolites into many end products. Recent engineering efforts have centered around harnessing the potential of these microbial biofactories for sustainable production of chemicals conventionally produced from fossil fuels. Here, we present an overview of the unique chemistry that cyanobacteria have been co-opted to perform. We highlight key lessons learned from these engineering efforts and discuss advantages and disadvantages of various approaches. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Does environmental archaeology need an ethical promise?

    DEFF Research Database (Denmark)

    Riede, Felix; Andersen, Per; Price, Neil

    2016-01-01

    Environmental catastrophes represent profound challenges faced by societies today. Numerous scholars in the climate sciences and the humanities have argued for a greater ethical engagement with these pressing issues. At the same time, several disciplines concerned with hazards are moving towards...... formalized ethical codes or promises that not only guide the dissemination of data but oblige scientists to relate to fundamentally political issues. This article couples a survey of the recent environmental ethics literature with two case studies of how past natural hazards have affected vulnerable...... societies in Europe?s prehistory. We ask whether cases of past calamities and their societal effects should play a greater role in public debates and whether archaeologists working with past environmental hazards should be more outspoken in their ethical considerations. We offer no firm answers, but suggest...

  12. Does environmental archaeology need an ethical promise?

    DEFF Research Database (Denmark)

    Riede, Felix; Andersen, Per; Price, Neil

    2016-01-01

    societies in Europe?s prehistory. We ask whether cases of past calamities and their societal effects should play a greater role in public debates and whether archaeologists working with past environmental hazards should be more outspoken in their ethical considerations. We offer no firm answers, but suggest......Environmental catastrophes represent profound challenges faced by societies today. Numerous scholars in the climate sciences and the humanities have argued for a greater ethical engagement with these pressing issues. At the same time, several disciplines concerned with hazards are moving towards...... formalized ethical codes or promises that not only guide the dissemination of data but oblige scientists to relate to fundamentally political issues. This article couples a survey of the recent environmental ethics literature with two case studies of how past natural hazards have affected vulnerable...

  13. Nanomedicine delivers promising treatments for rheumatoid arthritis.

    Science.gov (United States)

    Prasad, Leena Kumari; O'Mary, Hannah; Cui, Zhengrong

    2015-01-01

    An increased understanding in the pathophysiology of chronic inflammatory diseases, such as rheumatoid arthritis, reveals that the diseased tissue and the increased presence of macrophages and other overexpressed molecules within the tissue can be exploited to enhance the delivery of nanomedicine. Nanomedicine can passively accumulate into chronic inflammatory tissues via the enhanced permeability and retention phenomenon, or be surface conjugated with a ligand to actively bind to receptors overexpressed by cells within chronic inflammatory tissues, leading to increased efficacy and reduced systemic side-effects. This review highlights the research conducted over the past decade on using nanomedicine for potential treatment of rheumatoid arthritis and summarizes some of the major findings and promising opportunities on using nanomedicine to treat this prevalent and chronic disease.

  14. Anti-chemokine small molecule drugs: a promising future?

    Science.gov (United States)

    Proudfoot, Amanda E I; Power, Christine A; Schwarz, Matthias K

    2010-03-01

    Chemokines have principally been associated with inflammation due to their role in the control of leukocyte migration, but just over a decade ago chemokine receptors were also identified as playing a pivotal role in the entry of the HIV virus into cells. Chemokines activate seven transmembrane G protein-coupled receptors, making them extremely attractive therapeutic targets for the pharmaceutical industry. Although there are now a large number of molecules targeting chemokines and chemokine receptors including neutralizing antibodies in clinical trials for inflammatory diseases, the results to date have not always been positive, which has been disappointing for the field. These failures have often been attributed to redundancy in the chemokine system. However, other difficulties have been encountered in drug discovery processes targeting the chemokine system, and these will be addressed in this review. In this review, the reader will get an insight into the hurdles that have to be overcome, learn about some of the pitfalls that may explain the lack of success, and get a glimpse of the outlook for the future. In 2007, the FDA approved maraviroc, an inhibitor of CCR5 for the prevention of HIV infection, the first triumph for a small-molecule drug acting on the chemokine system. The time to market, 11 years from discovery of CCR5, was fast by industry standards. A second small-molecule drug, a CXCR4 antagonist for hematopoietic stem cell mobilization, was approved by the FDA at the end of 2008. The results of a Phase III trial with a CCR9 inhibitor for Crohn's disease are also promising. This could herald the first success for a chemokine receptor antagonist as an anti-inflammatory therapeutic and confirms the importance of chemokine receptors as a target class for anti-inflammatory and autoimmune diseases.

  15. GABARAPL1 antibodies: target one protein, get one free!

    Science.gov (United States)

    Le Grand, Jaclyn Nicole; Chakrama, Fatima Zahra; Seguin-Py, Stéphanie; Fraichard, Annick; Delage-Mourroux, Régis; Jouvenot, Michèle; Risold, Pierre-Yves; Boyer-Guittaut, Michaël

    2011-11-01

    Atg8 is a yeast protein involved in the autophagic process and in particular in the elongation of autophagosomes. In mammals, several orthologs have been identified and are classed into two subfamilies: the LC3 subfamily and the GABARAP subfamily, referred to simply as the LC3 or GABARAP families. GABARAPL1 (GABARAP-like protein 1), one of the proteins belonging to the GABARAP (GABA(A) receptor-associated protein) family, is highly expressed in the central nervous system and implicated in processes such as receptor and vesicle transport as well as autophagy. The proteins that make up the GABARAP family demonstrate conservation of their amino acid sequences and protein structures. In humans, GABARAPL1 shares 86% identity with GABARAP and 61% with GABARAPL2 (GATE-16). The identification of the individual proteins is thus very limited when working in vivo due to a lack of unique peptide sequences from which specific antibodies can be developed. Actually, and to our knowledge, there are no available antibodies on the market that are entirely specific to GABARAPL1 and the same may be true of the anti-GABARAP antibodies. In this study, we sought to examine the specificity of three antibodies targeted against different peptide sequences within GABARAPL1: CHEM-CENT (an antibody raised against a short peptide sequence within the center of the protein), PTG-NTER (an antibody raised against the N-terminus of the protein) and PTG-FL (an antibody raised against the full-length protein). The results described in this article demonstrate the importance of testing antibody specificity under the conditions for which it will be used experimentally, a caution that should be taken when studying the expression of the GABARAP family proteins.

  16. Antibodies: Computer-Aided Prediction of Structure and Design of Function.

    Science.gov (United States)

    Sevy, Alexander M; Meiler, Jens

    2014-12-01

    With the advent of high-throughput sequencing, and the increased availability of experimental structures of antibodies and antibody-antigen complexes, comes the improvement of computational approaches to predict the structure and design the function of antibodies and antibody-antigen complexes. While antibodies pose formidable challenges for protein structure prediction and design due to their large size and highly flexible loops in the complementarity-determining regions, they also offer exciting opportunities: the central importance of antibodies for human health results in a wealth of structural and sequence information that-as a knowledge base-can drive the modeling algorithms by limiting the conformational and sequence search space to likely regions of success. Further, efficient experimental platforms exist to test predicted antibody structure or designed antibody function, thereby leading to an iterative feedback loop between computation and experiment. We briefly review the history of computer-aided prediction of structure and design of function in the antibody field before we focus on recent methodological developments and the most exciting application examples.

  17. Dissecting Immunogenicity of Monoclonal Antibodies

    National Research Council Canada - National Science Library

    Snyder, Christopher

    2002-01-01

    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...

  18. 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...

  19. Antisperm antibodies and fertility association.

    Science.gov (United States)

    Restrepo, B; Cardona-Maya, W

    2013-10-01

    To evaluate the relation between antisperm antibodies (ASA) and human fertility by reviewing the scientific literature of the last 45 years. We carried out a review of scientific literature about antisperm antibodies and infertility published in spanish or english in databases as Pubmed, Medline, Scielo, some books and another gray literature include information related to this review and that is published in the last 45 years. Infertile couples suffer infertility by immunological mechanisms mainly by the presence of antisperm antibodies ASA in blood, semen or cervicovaginal secretions; the formation of ASA in men and women may be associated with disturbance in immunomodulatory mechanisms that result in functional impairment of sperm and thus its inability to fertilize the oocyte. Immunological infertility caused by ASA is the result of interference of these antibodies in various stages of fertilization process, inhibiting the ability of interaction between sperm and oocyte. Copyright © 2012 AEU. Published by Elsevier Espana. All rights reserved.

  20. Antibody Drug Conjugates: Preclinical Considerations.

    Science.gov (United States)

    Bornstein, Gadi G

    2015-05-01

    The development path for antibody drug conjugates (ADCs) is more complex and challenging than for unmodified antibodies. While many of the preclinical considerations for both unmodified and antibody drug conjugates are shared, special considerations must be taken into account when developing an ADC. Unlike unmodified antibodies, an ADC must preferentially bind to tumor cells, internalize, and traffic to the appropriate intracellular compartment to release the payload. Parameters that can impact the pharmacological properties of this class of therapeutics include the selection of the payload, the type of linker, and the methodology for payload drug conjugation. Despite a plethora of in vitro assays and in vivo models to screen and evaluate ADCs, the challenge remains to develop improved preclinical tools that will be more predictive of clinical outcome. This review will focus on preclinical considerations for clinically validated small molecule ADCs. In addition, the lessons learned from Mylotarg®, the first in class FDA-approved ADC, are highlighted.

  1. Medical big data: promise and challenges.

    Science.gov (United States)

    Lee, Choong Ho; Yoon, Hyung-Jin

    2017-03-01

    The concept of big data, commonly characterized by volume, variety, velocity, and veracity, goes far beyond the data type and includes the aspects of data analysis, such as hypothesis-generating, rather than hypothesis-testing. Big data focuses on temporal stability of the association, rather than on causal relationship and underlying probability distribution assumptions are frequently not required. Medical big data as material to be analyzed has various features that are not only distinct from big data of other disciplines, but also distinct from traditional clinical epidemiology. Big data technology has many areas of application in healthcare, such as predictive modeling and clinical decision support, disease or safety surveillance, public health, and research. Big data analytics frequently exploits analytic methods developed in data mining, including classification, clustering, and regression. Medical big data analyses are complicated by many technical issues, such as missing values, curse of dimensionality, and bias control, and share the inherent limitations of observation study, namely the inability to test causality resulting from residual confounding and reverse causation. Recently, propensity score analysis and instrumental variable analysis have been introduced to overcome these limitations, and they have accomplished a great deal. Many challenges, such as the absence of evidence of practical benefits of big data, methodological issues including legal and ethical issues, and clinical integration and utility issues, must be overcome to realize the promise of medical big data as the fuel of a continuous learning healthcare system that will improve patient outcome and reduce waste in areas including nephrology.

  2. Medical big data: promise and challenges

    Science.gov (United States)

    Lee, Choong Ho; Yoon, Hyung-Jin

    2017-01-01

    The concept of big data, commonly characterized by volume, variety, velocity, and veracity, goes far beyond the data type and includes the aspects of data analysis, such as hypothesis-generating, rather than hypothesis-testing. Big data focuses on temporal stability of the association, rather than on causal relationship and underlying probability distribution assumptions are frequently not required. Medical big data as material to be analyzed has various features that are not only distinct from big data of other disciplines, but also distinct from traditional clinical epidemiology. Big data technology has many areas of application in healthcare, such as predictive modeling and clinical decision support, disease or safety surveillance, public health, and research. Big data analytics frequently exploits analytic methods developed in data mining, including classification, clustering, and regression. Medical big data analyses are complicated by many technical issues, such as missing values, curse of dimensionality, and bias control, and share the inherent limitations of observation study, namely the inability to test causality resulting from residual confounding and reverse causation. Recently, propensity score analysis and instrumental variable analysis have been introduced to overcome these limitations, and they have accomplished a great deal. Many challenges, such as the absence of evidence of practical benefits of big data, methodological issues including legal and ethical issues, and clinical integration and utility issues, must be overcome to realize the promise of medical big data as the fuel of a continuous learning healthcare system that will improve patient outcome and reduce waste in areas including nephrology. PMID:28392994

  3. Candida Biofilms: Threats, Challenges, and Promising Strategies

    Science.gov (United States)

    Cavalheiro, Mafalda; Teixeira, Miguel Cacho

    2018-01-01

    Candida species are fungal pathogens known for their ability to cause superficial and systemic infections in the human host. These pathogens are able to persist inside the host due to the development of pathogenicity and multidrug resistance traits, often leading to the failure of therapeutic strategies. One specific feature of Candida species pathogenicity is their ability to form biofilms, which protects them from external factors such as host immune system defenses and antifungal drugs. This review focuses on the current threats and challenges when dealing with biofilms formed by Candida albicans, Candida glabrata, Candida tropicalis, and Candida parapsilosis, highlighting the differences between the four species. Biofilm characteristics depend on the ability of each species to produce extracellular polymeric substances (EPS) and display dimorphic growth, but also on the biofilm substratum, carbon source availability and other factors. Additionally, the transcriptional control over processes like adhesion, biofilm formation, filamentation, and EPS production displays great complexity and diversity within pathogenic yeasts of the Candida genus. These differences not only have implications in the persistence of colonization and infections but also on antifungal resistance typically found in Candida biofilm cells, potentiated by EPS, that functions as a barrier to drug diffusion, and by the overexpression of drug resistance transporters. The ability to interact with different species in in vivo Candida biofilms is also a key factor to consider when dealing with this problem. Despite many challenges, the most promising strategies that are currently available or under development to limit biofilm formation or to eradicate mature biofilms are discussed. PMID:29487851

  4. Promising Gene Therapeutics for Salivary Gland Radiotoxicity

    Directory of Open Access Journals (Sweden)

    Renjith Parameswaran Nair

    2016-11-01

    Full Text Available More than 0.5 million new cases of head and neck cancer are diagnosed worldwide each year, and approximately 75% of them are treated with radiation alone or in combination with other cancer treatments. A majority of patients treated with radiotherapy develop significant oral off-target effects because of the unavoidable irradiation of normal tissues. Salivary glands that lie within treatment fields are often irreparably damaged and a decline in function manifests as dry mouth or xerostomia. Limited ability of the salivary glands to regenerate lost acinar cells makes radiation-induced loss of function a chronic problem that affects the quality of life of the patients well beyond the completion of radiotherapy. The restoration of saliva production after irradiation has been a daunting challenge, and this review provides an overview of promising gene therapeutics that either improve the gland’s ability to survive radiation insult, or alternately, restore fluid flow after radiation. The salient features and shortcomings of each approach are discussed.

  5. Artificial Intelligence in Surgery: Promises and Perils.

    Science.gov (United States)

    Hashimoto, Daniel A; Rosman, Guy; Rus, Daniela; Meireles, Ozanan R

    2018-01-31

    The aim of this review was to summarize major topics in artificial intelligence (AI), including their applications and limitations in surgery. This paper reviews the key capabilities of AI to help surgeons understand and critically evaluate new AI applications and to contribute to new developments. AI is composed of various subfields that each provide potential solutions to clinical problems. Each of the core subfields of AI reviewed in this piece has also been used in other industries such as the autonomous car, social networks, and deep learning computers. A review of AI papers across computer science, statistics, and medical sources was conducted to identify key concepts and techniques within AI that are driving innovation across industries, including surgery. Limitations and challenges of working with AI were also reviewed. Four main subfields of AI were defined: (1) machine learning, (2) artificial neural networks, (3) natural language processing, and (4) computer vision. Their current and future applications to surgical practice were introduced, including big data analytics and clinical decision support systems. The implications of AI for surgeons and the role of surgeons in advancing the technology to optimize clinical effectiveness were discussed. Surgeons are well positioned to help integrate AI into modern practice. Surgeons should partner with data scientists to capture data across phases of care and to provide clinical context, for AI has the potential to revolutionize the way surgery is taught and practiced with the promise of a future optimized for the highest quality patient care.

  6. Endothelial Extracellular Vesicles-Promises and Challenges.

    Science.gov (United States)

    Hromada, Carina; Mühleder, Severin; Grillari, Johannes; Redl, Heinz; Holnthoner, Wolfgang

    2017-01-01

    Extracellular vesicles, including exosomes, microparticles, and apoptotic bodies, are phospholipid bilayer-enclosed vesicles that have once been considered as cell debris lacking biological functions. However, they have recently gained immense interest in the scientific community due to their role in intercellular communication, immunity, tissue regeneration as well as in the onset, and progression of various pathologic conditions. Extracellular vesicles of endothelial origin have been found to play a versatile role in the human body, since they are on the one hand known to contribute to cardiovascular diseases, but on the other hand have also been reported to promote endothelial cell survival. Hence, endothelial extracellular vesicles hold promising therapeutic potential to be used as a new tool to detect as well as treat a great number of diseases. This calls for clinically approved, standardized, and efficient isolation and characterization protocols to harvest and purify endothelial extracellular vesicles. However, such methods and techniques to fulfill stringent requirements for clinical trials have yet to be developed or are not harmonized internationally. In this review, recent advances and challenges in the field of endothelial extracellular vesicle research are discussed and current problems and limitations regarding isolation and characterization are pointed out.

  7. The Renewed Promise of Medical Informatics.

    Science.gov (United States)

    van Bemmel, J H; McCray, A T

    2016-05-20

    The promise of the field of Medical Informatics has been great and its impact has been significant. In 1999, the Yearbook editors of the International Medical Informatics Association (IMIA) - also the authors of the present paper - sought to assess this impact by selecting a number of seminal papers in the field, and asking experts to comment on these articles. In particular, it was requested whether and how the expectations, represented by these papers, had been fulfilled since their publication several decades earlier. Each expert was also invited to comment on what might be expected in the future. In the present paper, these areas are briefly reviewed again. Where did these early papers have an impact and where were they not as successful as originally expected? It should be noted that the extraordinary developments in computer technology observed in the last two decades could not have been foreseen by these early researchers. In closing, some of the possibilities and limitations of research in medical informatics are outlined in the context of a framework that considers six levels of computer applications in medicine and health care. For each level, some predictions are made for the future, concluded with thoughts on fruitful areas for ongoing research in the field.

  8. Medical big data: promise and challenges

    Directory of Open Access Journals (Sweden)

    Choong Ho Lee

    2017-03-01

    Full Text Available The concept of big data, commonly characterized by volume, variety, velocity, and veracity, goes far beyond the data type and includes the aspects of data analysis, such as hypothesis-generating, rather than hypothesis-testing. Big data focuses on temporal stability of the association, rather than on causal relationship and underlying probability distribution assumptions are frequently not required. Medical big data as material to be analyzed has various features that are not only distinct from big data of other disciplines, but also distinct from traditional clinical epidemiology. Big data technology has many areas of application in healthcare, such as predictive modeling and clinical decision support, disease or safety surveillance, public health, and research. Big data analytics frequently exploits analytic methods developed in data mining, including classification, clustering, and regression. Medical big data analyses are complicated by many technical issues, such as missing values, curse of dimensionality, and bias control, and share the inherent limitations of observation study, namely the inability to test causality resulting from residual confounding and reverse causation. Recently, propensity score analysis and instrumental variable analysis have been introduced to overcome these limitations, and they have accomplished a great deal. Many challenges, such as the absence of evidence of practical benefits of big data, methodological issues including legal and ethical issues, and clinical integration and utility issues, must be overcome to realize the promise of medical big data as the fuel of a continuous learning healthcare system that will improve patient outcome and reduce waste in areas including nephrology.

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. Antibodies are not required to a protective immune response against dengue virus elicited in a mouse encephalitis model.

    Science.gov (United States)

    Amorim, Jaime Henrique; dos Santos Alves, Rúbens Prince; Bizerra, Raíza; Araújo Pereira, Sara; Ramos Pereira, Lennon; Nascimento Fabris, Denicar Lina; Santos, Robert Andreata; Romano, Camila Malta; de Souza Ferreira, Luís Carlos

    2016-01-01

    Generating neutralizing antibodies have been considered a prerequisite to control dengue virus (DENV) infection. However, T lymphocytes have also been shown to be important in a protective immune state. In order to investigate the contribution of both humoral and cellular immune responses in DENV immunity, we used an experimental model in which a non-lethal DENV2 strain (ACS46) is used to intracranially prime Balb/C mice which develop protective immunity against a lethal DENV2 strain (JHA1). Primed mice generated envelope-specific antibodies and CD8(+) T cell responses targeting mainly non-structural proteins. Immune sera from protected mice did not confer passive protection to naïve mice challenged with the JHA1 strain. In contrast, depletion of CD4(+) and CD8(+) T lymphocytes significantly reduced survival of ACS46-primed mice challenged with the JHA1 strain. Collectively, results presented in this study show that a cellular immune response targeting non-structural proteins are a promising way in vaccine development against dengue. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Gene delivery into ischemic myocardium by double-targeted lipoplexes with anti-myosin antibody and TAT peptide.

    Science.gov (United States)

    Ko, Y T; Hartner, W C; Kale, A; Torchilin, V P

    2009-01-01

    The treatment of myocardial ischemia using gene therapy is a rather novel but promising approach. Gene delivery to target cells may be enhanced by using double-targeted delivery systems simultaneously capable of extracellular accumulation and intracellular penetration. With this in mind, we have used low cationic liposomes-plasmid DNA complexes (lipoplexes) modified with cell-penetrating transactivating transcriptional activator (TAT) peptide (TATp) and/or with monoclonal anti-myosin monoclonal antibody 2G4 (mAb 2G4) specific toward cardiac myosin, for targeted gene delivery to ischemic myocardium. In vitro transfection of both normoxic and hypoxic cardiomyocytes was enhanced by the presence of TATp as determined by fluorescence microscopy and ELISA. The in vitro transfection was further enhanced by the additional modification with mAb 2G4 antibody in the case of hypoxic, but not normoxic cardiomyocytes. However, we did not observe a synergism between TATp and mAb 2G4 ligands under our experimental condition. In in vivo experiments, we have clearly demonstrated an increased accumulation of mAb 2G4-modified TATp lipoplexes in the ischemic rat myocardium and significantly enhanced transfection of cardiomyocytes in the ischemic zone. Thus, the genetic transformation of normoxic and hypoxic cardiomyocytes can be enhanced by using lipoplexes modified with TATp and/or mAb 2G4. Such complexes also demonstrate an increased accumulation in the ischemic myocardium and effective transfection of hypoxic cardiomyocytes in vivo.

  15. Candida Biofilms: Threats, Challenges, and Promising Strategies

    Directory of Open Access Journals (Sweden)

    Mafalda Cavalheiro

    2018-02-01

    Full Text Available Candida species are fungal pathogens known for their ability to cause superficial and systemic infections in the human host. These pathogens are able to persist inside the host due to the development of pathogenicity and multidrug resistance traits, often leading to the failure of therapeutic strategies. One specific feature of Candida species pathogenicity is their ability to form biofilms, which protects them from external factors such as host immune system defenses and antifungal drugs. This review focuses on the current threats and challenges when dealing with biofilms formed by Candida albicans, Candida glabrata, Candida tropicalis, and Candida parapsilosis, highlighting the differences between the four species. Biofilm characteristics depend on the ability of each species to produce extracellular polymeric substances (EPS and display dimorphic growth, but also on the biofilm substratum, carbon source availability and other factors. Additionally, the transcriptional control over processes like adhesion, biofilm formation, filamentation, and EPS production displays great complexity and diversity within pathogenic yeasts of the Candida genus. These differences not only have implications in the persistence of colonization and infections but also on antifungal resistance typically found in Candida biofilm cells, potentiated by EPS, that functions as a barrier to drug diffusion, and by the overexpression of drug resistance transporters. The ability to interact with different species in in vivo Candida biofilms is also a key factor to consider when dealing with this problem. Despite many challenges, the most promising strategies that are currently available or under development to limit biofilm formation or to eradicate mature biofilms are discussed.

  16. Secukinumab: a promising therapeutic option in spondyloarthritis.

    Science.gov (United States)

    Maldonado-Ficco, Hernan; Perez-Alamino, Rodolfo; Maldonado-Cocco, José A

    2016-09-01

    Psoriatic arthritis (PsA) is the second most common chronic inflammatory joint disease. Ankylosing spondylitis (AS) is another less common but equally chronic and disabling spondyloarthritis (SpA). Therapeutic agents for the treatment of these diseases have been somewhat lacking as compared with those available for rheumatoid arthritis, which represents a significant challenge for both the treating physician and the pharmaceutical industry. A promising development for our understanding of the physiopathology of PsA and AS involves new targets to interrupt IL-17 and IL-12/IL-23 pathways. Up to 30-40 % of SpA patients have inadequate or poor response, or are intolerant to anti-TNF therapies. Therefore, there has been a clear unmet medical need in an important group of these patients. As a result, new therapeutic targets have emerged for the treatment of both axial and peripheral SpA. Interleukin 17 (IL-17) is a pro-inflammatory cytokine that is increased in psoriatic lesions as well as in the synovial fluid of patients with PsA and in sites of enthesitis in SpA. IL-23 has been shown to play an important role in the polarization of CD4+ T-cells to become IL-17 producers. Based on these evidences, blockade of the cytokine IL-17 or its receptors was considered to have therapeutic implications for the treatment of psoriasis, as well as PsA and AS.This article presents a thorough review of an IL-17 A blocking agent, its mechanism of action, its clinical efficacy and its therapeutic safety.

  17. Enantioselectivity of mass spectrometry: challenges and promises.

    Science.gov (United States)

    Awad, Hanan; El-Aneed, Anas

    2013-01-01

    With the fast growing market of pure enantiomer drugs and bioactive molecules, new chiral-selective analytical tools have been instigated including the use of mass spectrometry (MS). Even though MS is one of the best analytical tools that has efficiently been used in several pharmaceutical and biological applications, traditionally MS is considered as a "chiral-blind" technique. This limitation is due to the MS inability to differentiate between two enantiomers of a chiral molecule based merely on their masses. Several approaches have been explored to assess the potential role of MS in chiral analysis. The first approach depends on the use of MS-hyphenated techniques utilizing fast and sensitive chiral separation tools such as liquid chromatography (LC), gas chromatography (GC), and capillary electrophoresis (CE) coupled to MS detector. More recently, several alternative separation techniques have been evaluated such as supercritical fluid chromatography (SFC) and capillary electrochromatography (CEC); the latter being a hybrid technique that combines the efficiency of CE with the selectivity of LC. The second approach is based on using the MS instrument solely for the chiral recognition. This method depends on the behavioral differences between enantiomers towards a foreign molecule and the ability of MS to monitor such differences. These behavioral differences can be divided into three types: (i) differences in the enantiomeric affinity for association with the chiral selector, (ii) differences of the enantiomeric exchange rate with a foreign reagent, and (iii) differences in the complex MS dissociation behaviors of the enantiomers. Most recently, ion mobility spectrometry was introduced to qualitatively and quantitatively evaluate chiral compounds. This article provides an overview of MS role in chiral analysis by discussing MS based methodologies and presenting the challenges and promises associated with each approach. © 2013 Wiley Periodicals, Inc.

  18. The promise of innovation: Nuclear energy horizons

    International Nuclear Information System (INIS)

    Mourogov, V.

    2003-01-01

    The 21st century promises the most open, competitive, and globalized markets in human history, as well as the most rapid pace of technological change ever. For nuclear energy, as any other, that presents challenges. Though the atom now supplies a good share of world electricity, its share of total energy is relatively small, anywhere from four to six per cent depending on how it is calculated. And, while energy is most needed in the developing world, four of every five nuclear plants are in industrialized countries. Critical problems that need to be overcome are well known - high capital costs for new plants, and concerns over proliferation risks and safety, (including safety of waste disposal) stand high among them. The IAEA and other programmes are confronting these problems through ambitious initiatives involving both industrialized and developing countries. They include the collaborative efforts known as the Generation-IV International Forum (GIF) and the IAEA International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO). They use ideas, results and the best experiences from today's research and development tools and advanced types of nuclear energy systems to meet tomorrow's challenges. Though the market often decides the fate of new initiatives, the market is not always right for the common good. Governments, and the people that influence them, play an indispensable role in shaping progress in energy fields for rich and poor countries alike. They shoulder the main responsibilities for fundamental science, basic research, and long-term investments. For energy in particular, government investment and support will prove instrumental in the pace of innovation toward long-term options that are ready to replace limited fossil fuel supplies, and respond to the growing premium put on clean energy alternatives. Yet governments cannot go it alone. The challenges are too diverse and complex, and public concerns - about proliferation or safety - go beyond

  19. Review of Current Cell-Penetrating Antibody Developments for HIV-1 Therapy

    Directory of Open Access Journals (Sweden)

    Muhamad Alif Che Nordin

    2018-02-01

    Full Text Available The discovery of highly active antiretroviral therapy (HAART in 1996 has significantly reduced the global mortality and morbidity caused by the acquired immunodeficiency syndrome (AIDS. However, the therapeutic strategy of HAART that targets multiple viral proteins may render off-target toxicity and more importantly results in drug-resistant escape mutants. These have been the main challenges for HAART and refinement of this therapeutic strategy is urgently needed. Antibody-mediated treatments are emerging therapeutic modalities for various diseases. Most therapeutic antibodies have been approved by Food and Drug Administration (FDA mainly for targeting cancers. Previous studies have also demonstrated the promising effect of therapeutic antibodies against HIV-1, but there are several limitations in this therapy, particularly when the viral targets are intracellular proteins. The conventional antibodies do not cross the cell membrane, hence, the pathogenic intracellular proteins cannot be targeted with this classical therapeutic approach. Over the years, the advancement of antibody engineering has permitted the therapeutic antibodies to comprehensively target both extra- and intra-cellular proteins in various infections and diseases. This review aims to update on the current progress in the development of antibody-based treatment against intracellular targets in HIV-1 infection. We also attempt to highlight the challenges and limitations in the development of antibody-based therapeutic modalities against HIV-1.

  20. In Situ Liver Expression of HBsAg/CD3-Bispecific Antibodies for HBV Immunotherapy

    Directory of Open Access Journals (Sweden)

    Robert L. Kruse

    2017-12-01

    Full Text Available Current therapies against hepatitis B virus (HBV do not reliably cure chronic infection, necessitating new therapeutic approaches. The T cell response can clear HBV during acute infection, and the adoptive transfer of antiviral T cells during bone marrow transplantation can cure patients of chronic HBV infection. To redirect T cells to HBV-infected hepatocytes, we delivered plasmids encoding bispecific antibodies directed against the viral surface antigen (HBsAg and CD3, expressed on almost all T cells, directly into the liver using hydrodynamic tail vein injection. We found a significant reduction in HBV-driven reporter gene expression (184-fold in a mouse model of acute infection, which was 30-fold lower than an antibody only recognizing HBsAg. While bispecific antibodies triggered, in part, antigen-independent T cell activation, antibody production within hepatocytes was non-cytotoxic. We next tested the bispecific antibodies in a different HBV mouse model, which closely mimics the transcriptional template for HBV, covalently closed circular DNA (cccDNA. We found that the antiviral effect was noncytopathic, mediating a 495-fold reduction in HBsAg levels at day 4. At day 33, bispecific antibody-treated mice exhibited 35-fold higher host HBsAg immunoglobulin G (IgG antibody production versus untreated groups. Thus, gene therapy with HBsAg/CD3-bispecific antibodies represents a promising therapeutic strategy for patients with HBV.

  1. Efficient method to optimize antibodies using avian leukosis virus display and eukaryotic cells.

    Science.gov (United States)

    Yu, Changming; Pike, Gennett M; Rinkoski, Tommy A; Correia, Cristina; Kaufmann, Scott H; Federspiel, Mark J

    2015-08-11

    Antibody-based therapeutics have now had success in the clinic. The affinity and specificity of the antibody for the target ligand determines the specificity of therapeutic delivery and off-target side effects. The discovery and optimization of high-affinity antibodies to important therapeutic targets could be significantly improved by the availability of a robust, eukaryotic display technology comparable to phage display that would overcome the protein translation limitations of microorganisms. The use of eukaryotic cells would improve the diversity of the displayed antibodies that can be screened and optimized as well as more seamlessly transition into a large-scale mammalian expression system for clinical production. In this study, we demonstrate that the replication and polypeptide display characteristics of a eukaryotic retrovirus, avian leukosis virus (ALV), offers a robust, eukaryotic version of bacteriophage display. The binding affinity of a model single-chain Fv antibody was optimized by using ALV display, improving affinity >2,000-fold, from micromolar to picomolar levels. We believe ALV display provides an extension to antibody display on microorganisms and offers virus and cell display platforms in a eukaryotic expression system. ALV display should enable an improvement in the diversity of properly processed and functional antibody variants that can be screened and affinity-optimized to improve promising antibody candidates.

  2. Role of plant expression systems in antibody production for passive immunization.

    Science.gov (United States)

    Virdi, Vikram; Depicker, Ann

    2013-01-01

    Passive immunization is a method to achieve immediate protection against infectious agents by administering pathogen-specific antibodies. It has proven to be lifesaving for many acute infections, and it is now also used for cancer treatment. Passive immunization therapies, however, are extremely expensive because they require large amounts of specific antibodies that are produced predominantly in mammalian expression systems. The cost for manufacturing plant-made antibodies is estimated to be comparatively low since plant production systems require relatively less capital investments. In addition, they are not prone to mammalian pathogens, which also eases downstream processing along with making it a safe expression system. Moreover, some of the recent developments in transient expression have enabled rapid, cGMP (current Good Manufacturing Practices) compliant manufacturing of antibodies. Whether lower production costs will be reflected in a lower market price for purified antibodies will be known when more plant-produced antibodies come to the market. Promisingly, the current molecular techniques in the field of in planta expression have enabled high-level production of a variety of antibodies in different plant organs, like roots/tubers/fruits, leaves and seeds, of a variety of plants, like potato, tobacco, maize, rice, tomato and pea, providing a very wide range of possible plant-based passive immunization therapies. For instance, the production of antibodies in edible tissues would allow for a unique, convenient, needle-less, oral passive immunization at the gastric mucosal surface. The technological advances, together with the innate capacity of plant tissues to assemble complex antibodies, will enable carving a niche in the antibody market. This non-exhaustive review aims to shed light on the role of plants as a flexible expression system for passive immunotherapy, which we envisage to progress alongside the conventional production platforms to manufacture

  3. Replacing reprogramming factors with antibodies selected from combinatorial antibody libraries.

    Science.gov (United States)

    Blanchard, Joel W; Xie, Jia; El-Mecharrafie, Nadja; Gross, Simon; Lee, Sohyon; Lerner, Richard A; Baldwin, Kristin K

    2017-10-01

    The reprogramming of differentiated cells into induced pluripotent stem cells (iPSCs) is usually achieved by exogenous induction of transcription by factors acting in the nucleus. In contrast, during development, signaling pathways initiated at the membrane induce differentiation. The central idea of this study is to identify antibodies that can catalyze cellular de-differentiation and nuclear reprogramming by acting at the cell surface. We screen a lentiviral library encoding ∼100 million secreted and membrane-bound single-chain antibodies and identify antibodies that can replace either Sox2 and Myc (c-Myc) or Oct4 during reprogramming of mouse embryonic fibroblasts into iPSCs. We show that one Sox2-replacing antibody antagonizes the membrane-associated protein Basp1, thereby de-repressing nuclear factors WT1, Esrrb and Lin28a (Lin28) independent of Sox2. By manipulating this pathway, we identify three methods to generate iPSCs. Our results establish unbiased selection from autocrine combinatorial antibody libraries as a robust method to discover new biologics and uncover membrane-to-nucleus signaling pathways that regulate pluripotency and cell fate.

  4. Cancer Imaging and Therapy with Bispecific Antibody Pretargeting.

    Science.gov (United States)

    Goldenberg, David M; Chatal, Jean-Francois; Barbet, Jacques; Boerman, Otto; Sharkey, Robert M

    2007-03-01

    This article reviews recent preclinical and clinical advances in the use of pretargeting methods for the radioimmunodetection and radioimmunotherapy of cancer. Whereas directly-labeled antibodies, fragments, and subfragments (minibodies and other constructs) have shown promise in both imaging and therapy applications over the past 25 years, their clinical adoption has not fulfilled the original expectations due to either poor image resolution and contrast in scanning or insufficient radiation doses delivered selectively to tumors for therapy. Pretargeting involves the separation of the localization of tumor with an anticancer antibody from the subsequent delivery of the imaging or therapeutic radionuclide. This has shown improvements in both imaging and therapy by overcoming the limitations of conventional, or 1-step, radioimmunodetection or radioimmunotherapy. We focus herein on the use of bispecific antibodies followed by radiolabeled peptide haptens as a new modality of selective delivery of radionuclides for the imaging and therapy of cancer. Our particular emphasis in pretargeting is the use of bispecific trimeric (3 Fab's) recombinant constructs made by a modular method of antibody and protein engineering of fusion molecules called Dock and Lock (DNL).

  5. 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.)

  6. Antibody Validation by Western Blotting.

    Science.gov (United States)

    Signore, Michele; Manganelli, Valeria; Hodge, Alex

    2017-01-01

    Validation of antibodies is an integral part of translational research, particularly for biomarker discovery. Assaying the specificity of the reagent (antibody) and confirming the identity of the protein biomarker is of critical importance prior to implementing any biomarker in clinical studies, and the lack of such quality control tests may result in unexpected and/or misleading results.Antibody validation is the procedure in which a single antibody is thoroughly assayed for sensitivity and specificity. Although a plethora of commercial antibodies exist, antibody specificity must be extensively demonstrated using diverse complex biological samples, rather than purified recombinant proteins, prior to use in clinical translational research. In the simplest iteration, antibody specificity is determined by the presence of a single band in a complex biological sample, at the expected molecular weight, on a Western blot.To date, numerous Western blotting procedures are available, based on either manual or automated systems and spanning the spectrum of single blots to multiplex blots. X-ray film is still employed in many research laboratories, but digital imaging has become a gold standard in immunoblotting. The basic principles of Western blotting are (a) separation of protein mixtures by gel electrophoresis, (b) transfer of the proteins to a blot, (c) probing the blot for a protein or proteins of interest, and (d) subsequent detection of the protein by chemiluminescent, fluorescent, or colorimetric methods. This chapter focuses on the chemiluminescent detection of proteins using a manual Western blotting system and a vacuum-enhanced detection system (SNAP i.d.™, Millipore).

  7. Green and social bonds - A promising tool

    International Nuclear Information System (INIS)

    Blanc, Dominique; Barochez, Aurelie de; Cozic, Aela

    2013-11-01

    Issues of green bonds, socially responsible bonds and climate bonds are on the rise. Novethic estimates that some Euro 5 billion in such bonds has been issued since the start of 2013 by development banks, the main issuers of this type of debt. The figure is equal to over half of their total issues since 2007. Including local authorities, corporations and banks, a total Euro 8 billion of these bonds has been issued thus far in 2013. Given the size of the bond market, which the OECD estimated at Euro 95,000 billion in 2011, green and social bonds are still something of a niche but have strong growth potential. A number of large issues, from Euro 500 million to Euro 1 billion, were announced at the end of the year. Unlike conventional bonds, green and social bonds are not intended to finance all the activities of the issuer or refinance its debt. They serve instead to finance specific projects, such as producing renewable energy or adapting to climate change, the risk of which is shouldered by the issuer. This makes them an innovative instrument, used to earmark investments in projects with a direct environmental or social benefit rather than simply on the basis of the issuer's sustainable development policy. With financing being sought for the ecological transition, green and social bonds are promising instruments, sketching out at global level the shape of tools adapted to the financing of a green economy. On the strength of these advantages, the interest of responsible investors - the main target of green and social bond issuers - is growing fast. Judging by issuer press releases and the most commonly used currencies, the main subscribers today are US investors, among them CalSTRS and fund managers like Calvert Investment Management and Trillium Asset Management. European asset owners are also starting to focus on green and social bonds. A Novethic survey shows that 13% of them have already subscribed to such an issue or plan to do so. The present study

  8. Correlated effects of selection for immunity in White Leghorn chicken lines on natural antibodies and specific antibody responses to KLH and M. butyricum

    OpenAIRE

    Minozzi, Giulietta; Parmentier, Henk K; Mignon-Grasteau, Sandrine; Nieuwland, Mike GB; Bed'hom, Bertrand; Gourichon, David; Minvielle, Francis; Pinard-van der Laan, Marie-Helen

    2008-01-01

    Background - The effect of selection for three general immune response traits on primary antibody responses (Ab) to Mycobacterium butyricum or keyhole limpet hemocyanin (KLH) was studied in four experimental lines of White Leghorn chicken. Birds underwent 12 generations of selection for one of three different general immune criteria; high antibody response to Newcastle disease virus 3 weeks after vaccination (ND3), high cell-mediated immune response, using the wing web response to phytohemglu...

  9. Protein Replacement Therapy Shows Promise in Treating Rare Skin Disorder

    Science.gov (United States)

    ... Room Spotlight on Research Spotlight on Research Protein Replacement Therapy Shows Promise in Treating Rare Skin Disorder ... are under development. One promising approach involves protein replacement. Previous research has suggested that replacing the missing ...

  10. Rationalization and Design of the Complementarity Determining Region Sequences in an Antibody-Antigen Recognition Interface

    Science.gov (United States)

    Chen, Ing-Chien; Lee, Yu-Ching; Chen, Jun-Bo; Tsai, Keng-Chang; Chen, Ching-Tai; Chang, Jeng-Yih; Yang, Ei-Wen; Hsu, Po-Chiang; Jian, Jhih-Wei; Hsu, Hung-Ju; Chang, Hung-Ju; Hsu, Wen-Lian; Huang, Kai-Fa; Ma, Alex Che; Yang, An-Suei

    2012-01-01

    Protein-protein interactions are critical determinants in biological systems. Engineered proteins binding to specific areas on protein surfaces could lead to therapeutics or diagnostics for treating diseases in humans. But designing epitope-specific protein-protein interactions with computational atomistic interaction free energy remains a difficult challenge. Here we show that, with the antibody-VEGF (vascular endothelial growth factor) interaction as a model system, the experimentally observed amino acid preferences in the antibody-antigen interface can be rationalized with 3-dimensional distributions of interacting atoms derived from the database of protein structures. Machine learning models established on the rationalization can be generalized to design amino acid preferences in antibody-antigen interfaces, for which the experimental validations are tractable with current high throughput synthetic antibody display technologies. Leave-one-out cross validation on the benchmark system yielded the accuracy, precision, recall (sensitivity) and specificity of the overall binary predictions to be 0.69, 0.45, 0.63, and 0.71 respectively, and the overall Matthews correlation coefficient of the 20 amino acid types in the 24 interface CDR positions was 0.312. The structure-based computational antibody design methodology was further tested with other antibodies binding to VEGF. The results indicate that the methodology could provide alternatives to the current antibody technologies based on animal immune systems in engineering therapeutic and diagnostic antibodies against predetermined antigen epitopes. PMID:22457753

  11. Radiosensitivity of antibody responses and radioresistant secondary tetanus antitoxin responses

    International Nuclear Information System (INIS)

    Stoner, R.; Terres, G.; Cottier, H.; Hess, M.

    1976-01-01

    Primary tetanus antitoxin responses were increasingly repressed in mice when gamma radiation doses of 100 to 400 rads were delivered by whole-body exposure prior to immunization with fluid tetanus toxoid (FTT). Nearly normal secondary antitoxin responses were obtained in mice exposed to 600 rads of gamma radiation 4 days after secondary antigenic stimulation with FTT. A rapid transition from radiosensitivity of the antibody-forming system on days 1 to 3 was followed by relative radioresistance on day 4 after the booster injection of toxoid. Studies on lymphoid cellular kinetics in popliteal lymph nodes after injection of 3 H--thymidine ( 3 H--TdR) and incorporation of 3 H--L-histidine into circulating antitoxin were carried out. Analysis of tritium radioactivity in antigen--antibody precipitates of serums 2 hr after injection of the labeled amino acid revealed maximum incorporation into antibody around day 7 after the booster in nonirradiated controls and about day 12, i.e., 8 days after irradiation, in experimental mice. The shift from radiosensitivity to relative radioresistance was attributed to a marked peak of plasma-cell proliferation in the medulla of lymph nodes on day 3. Many medullary plasma cells survived and continued to proliferate after exposure to radiation. Germinal centers were destroyed by radiation within 1 day. Since antibody formation continued after exposure to radiation and after the loss of germinal centers, this supports the view that germinal-center cells were involved more in the generation of memory cells than in antibody synthesis

  12. 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.)

  13. Novel Antibody-Based Proteins for Cancer Immunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Fuenmayor, Jaheli; Montaño, Ramon F., E-mail: jfuenmay@ivic.gob.ve [Laboratorio de Patología Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas. Caracas, 1020-A (Venezuela, Bolivarian Republic of)

    2011-08-19

    The relative success of monoclonal antibodies in cancer immunotherapy and the vast manipulation potential of recombinant antibody technology have encouraged the development of novel antibody-based antitumor proteins. Many insightful reagents have been produced, mainly guided by studies on the mechanisms of action associated with complete and durable remissions, results from experimental animal models, and our current knowledge of the human immune system. Strikingly, only a small percent of these new reagents has demonstrated clinical value. Tumor burden, immune evasion, physiological resemblance, and cell plasticity are among the challenges that cancer therapy faces, and a number of antibody-based proteins are already available to deal with many of them. Some of these novel reagents have been shown to specifically increase apoptosis/cell death of tumor cells, recruit and activate immune effectors, and reveal synergistic effects not previously envisioned. In this review, we look into different approaches that have been followed during the past few years to produce these biologics and analyze their relative success, mainly in terms of their clinical performance. The use of antibody-based antitumor proteins, in combination with standard or novel therapies, is showing significant improvements in objective responses, suggesting that these reagents will become important components of the antineoplastic protocols of the future.

  14. Recent Developments in Antibody-Based Assays for the Detection of Bacterial Toxins

    Directory of Open Access Journals (Sweden)

    Kui Zhu

    2014-04-01

    Full Text Available Considering the urgent demand for rapid and accurate determination of bacterial toxins and the recent promising developments in nanotechnology and microfluidics, this review summarizes new achievements of the past five years. Firstly, bacterial toxins will be categorized according to their antibody binding properties into low and high molecular weight compounds. Secondly, the types of antibodies and new techniques for producing antibodies are discussed, including poly- and mono-clonal antibodies, single-chain variable fragments (scFv, as well as heavy-chain and recombinant antibodies. Thirdly, the use of different nanomaterials, such as gold nanoparticles (AuNPs, magnetic nanoparticles (MNPs, quantum dots (QDs and carbon nanomaterials (graphene and carbon nanotube, for labeling antibodies and toxins or for readout techniques will be summarized. Fourthly, microscale analysis or minimized devices, for example microfluidics or lab-on-a-chip (LOC, which have attracted increasing attention in combination with immunoassays for the robust detection or point-of-care testing (POCT, will be reviewed. Finally, some new materials and analytical strategies, which might be promising for analyzing toxins in the near future, will be shortly introduced.

  15. Improving properties of llama heavy chain antibodies using in silico analysis

    NARCIS (Netherlands)

    Lutje Hulsik, D.

    2009-01-01

    Microbicides offer a promising way to prevent HIV infection in developing countries. Llama heavy chain antibody fragments (VHHs) that neutralize HIV are an ideal candidate for usage as active microbicide component. A VHH is the smallest intact antigen binding domain which allows it to reach for

  16. Western Blotting Inaccuracies with Unverified Antibodies: Need for a Western Blotting Minimal Reporting Standard (WBMRS).

    Science.gov (United States)

    Gilda, Jennifer E; Ghosh, Rajeshwary; Cheah, Jenice X; West, Toni M; Bodine, Sue C; Gomes, Aldrin V

    2015-01-01

    Western blotting is a commonly used technique in biological research. A major problem with Western blotting is not the method itself, but the use of poor quality antibodies as well as the use of different experimental conditions that affect the linearity and sensitivity of the Western blot. Investigation of some conditions that are commonly used and often modified in Western blotting, as well as some commercial antibodies, showed that published articles often fail to report critical parameters needed to reproduce the results. These parameters include the amount of protein loaded, the blocking solution and conditions used, the amount of primary and secondary antibodies used, the antibody incubation solutions, the detection method and the quantification method utilized. In the present study, comparison of ubiquitinated proteins in rat heart and liver samples showed different results depending on the antibody utilized. Validation of five commercial ubiquitin antibodies using purified ubiquitinated proteins, ubiquitin chains and free ubiquitin showed that these antibodies differ in their ability to detect free ubiquitin or ubiquitinated proteins. Investigating proteins modified with interferon-stimulated gene 15 (ISG15) in young and old rat hearts using six commercially available antibodies showed that most antibodies gave different semi-quantitative results, suggesting large variability among antibodies. Evidence showing the importance of the Western blot buffer and the concentration of antibody used is presented. Hence there is a critical need for comprehensive reporting of experimental conditions to improve the accuracy and reproducibility of Western blot analysis. A Western blotting minimal reporting standard (WBMRS) is suggested to improve the reproducibility of Western blot analysis.

  17. Modelling of potentially promising SARS protease inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Plewczynski, Dariusz [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland); Hoffmann, Marcin [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Grotthuss, Marcin von [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Knizewski, Lukasz [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland); Rychewski, Leszek [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Eitner, Krystian [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Ginalski, Krzysztof [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland)

    2007-07-18

    In many cases, at the beginning of a high throughput screening experiment some information about active molecules is already available. Active compounds (such as substrate analogues, natural products and inhibitors of related proteins) are often identified in low throughput validation studies on a biochemical target. Sometimes the additional structural information is also available from crystallographic studies on protein and ligand complexes. In addition, the structural or sequence similarity of various protein targets yields a novel possibility for drug discovery. Co-crystallized compounds from homologous proteins can be used to design leads for a new target without co-crystallized ligands. In this paper we evaluate how far such an approach can be used in a real drug campaign, with severe acute respiratory syndrome (SARS) coronavirus providing an example. Our method is able to construct small molecules as plausible inhibitors solely on the basis of the set of ligands from crystallized complexes of a protein target, and other proteins from its structurally homologous family. The accuracy and sensitivity of the method are estimated here by the subsequent use of an electronic high throughput screening flexible docking algorithm. The best performing ligands are then used for a very restrictive similarity search for potential inhibitors of the SARS protease within the million compounds from the Ligand.Info small molecule meta-database. The selected molecules can be passed on for further experimental validation.

  18. Legal implications of translational promises of unproven stem cell ...

    African Journals Online (AJOL)

    The promise stem cell therapy holds for curing diseases for which no therapy currently exists is often translated as fact. Unfortunately, enforced misconceptions between fact and promise often also translate into exploitation and harming of patients. This article aims to clear up misconceptions about the biological promise ...

  19. Prosecuting the Leaders: Promises, Politics and Practicalities

    Directory of Open Access Journals (Sweden)

    Robert Cryer

    2009-02-01

    Full Text Available Given recent developments in relation to the prosecution of international crimes,  it might be thought that one of the last bastions of sovereignty has been breached, and international criminal law has not only entrenched itself in international law. Indeed further to this, it has assumed a supranational position that stands entirely above States, promising justice for all and as a trump card over depredations committed in the name of State sovereignty. After all, Charles Taylor from Liberia is standing trial before the Special Court for Sierra Leone, Slobodan Milošević only escaped judgment by the International Criminal Tribunal for the former

  20. Diagnostic utility of egg yolk for the detection of avian metapneumovirus antibodies in laying hens.

    Science.gov (United States)

    Choi, Kang-Seuk; Lee, Eun-Kyoung; Jeon, Woo-Jin; Park, Mi-Ja; Yoo, Yae-Na; Kwon, Jun-Hun

    2010-12-01

    Surveillance and diagnosis of avian metapneumovirus (AMPV) infection typically involve measurement of serum antibodies. In the current study, eggs instead of serum samples were used for the detection of AMPV antibodies in egg-laying chicken hens by enzyme-linked immunosorbent assay (ELISA). AMPV-free commercial layer hens were experimentally challenged with AMPV strain SC1509 through intravenous or oculonasal administration. Antibody levels were determined by ELISA. AMPV antibodies were detected in egg yolks from challenged hens by 7 days postinoculation (dpi), with the peak titer at 16 dpi. Antibody levels in eggs laid at 28 dpi correlated well (r = 0.93) with sera taken 28 dpi from the same hens. In a field trial of the yolk ELISA, six broiler breeder farms were surveyed, and all tested positive for AMPV antibodies in hen eggs, although positivity varied from farm to farm. Abnormal discolored eggs collected from outbreak farms had significantly higher titers of AMPV yolk antibodies than normal eggs from the same farm, unlike clinically healthy farms, where normal and abnormal eggs had similar antibody titers. These results indicate that diagnosis of AMPV infection by yolk ELISA to detect anti-AMPV antibodies may be a suitable alternative to serologic testing.

  1. Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters.

    Directory of Open Access Journals (Sweden)

    Oliver F Brandenberg

    2017-05-01

    Full Text Available The potential of broadly neutralizing antibodies targeting the HIV-1 envelope trimer to prevent HIV-1 transmission has opened new avenues for therapies and vaccines. However, their implementation remains challenging and would profit from a deepened mechanistic understanding of HIV-antibody interactions and the mucosal transmission process. In this study we experimentally determined stoichiometric parameters of the HIV-1 trimer-antibody interaction, confirming that binding of one antibody is sufficient for trimer neutralization. This defines numerical requirements for HIV-1 virion neutralization and thereby enables mathematical modelling of in vitro and in vivo antibody neutralization efficacy. The model we developed accurately predicts antibody efficacy in animal passive immunization studies and provides estimates for protective mucosal antibody concentrations. Furthermore, we derive estimates of the probability for a single virion to start host infection and the risks of male-to-female HIV-1 transmission per sexual intercourse. Our work thereby delivers comprehensive quantitative insights into both the molecular principles governing HIV-antibody interactions and the initial steps of mucosal HIV-1 transmission. These insights, alongside the underlying, adaptable modelling framework presented here, will be valuable for supporting in silico pre-trial planning and post-hoc evaluation of HIV-1 vaccination or antibody treatment trials.

  2. Genetically Modified Crops: Risks and Promise

    Directory of Open Access Journals (Sweden)

    Gordon Conway

    2000-07-01

    Full Text Available GM foods have the potential to provide significant benefits for developing countries. Over 800 million people are chronically undernourished, and 180 million children are severely underweight for their age. By 2020, there will be an extra two billion mouths to feed. Ecological approaches that underpin sustainable agriculture (e.g., integrated pest management and participatory approaches that strengthen farmers' own experimentation and decision making are key. Biotechnology will be an essential partner, if yield ceilings are to be raised, if crops are to be grown without excessive reliance on pesticides, and if farmers on less favored lands are to be provided with crops that are resistant to drought and salinity, and that can use nitrogen and other nutrients more efficiently. Over the past 10 years, in addition supporting ecological approaches, the Rockefeller Foundation has funded the training of some 400 developing-country scientists in the techniques of biotechnology. Most of the new crop varieties are the result of tissue culture and marker-aided selection. The Foundation also supports the production of genetically engineered rices, including a new rice engineered for beta carotene (the precursor of Vitamin A in the grain. Some specific steps can be taken by Monsanto that would improve acceptance of plant biotechnology in both the developing and the industrialized worlds: label; disavow gene protection (terminator systems; phase out the use of antibiotic resistance markers; agree (with big seed companies to use the plant variety protection system, rather than patents, in developing countries; establish an independently administered fellowship program to train developing-country scientists in crop biotechnology, biosafety, and intellectual property; donate useful technologies to developing countries; agree to share financial rewards from intellectual property rights on varieties such as basmati or jasmine rice with the countries of origin; and

  3. 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.

  4. Antibody profiling sensitivity through increased reporter antibody layering

    International Nuclear Information System (INIS)

    Apel, William A.; Thompson, Vickie S.

    2013-01-01

    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.

  5. 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.

  6. 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.

  7. 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.

  8. Medaka: a promising model animal for comparative population genomics

    Directory of Open Access Journals (Sweden)

    Watanabe Koji

    2009-05-01

    Full Text Available Abstract Background Within-species genome diversity has been best studied in humans. The international HapMap project has revealed a tremendous amount of single-nucleotide polymorphisms (SNPs among humans, many of which show signals of positive selection during human evolution. In most of the cases, however, functional differences between the alleles remain experimentally unverified due to the inherent difficulty of human genetic studies. It would therefore be highly useful to have a vertebrate model with the following characteristics: (1 high within-species genetic diversity, (2 a variety of gene-manipulation protocols already developed, and (3 a completely sequenced genome. Medaka (Oryzias latipes and its congeneric species, tiny fresh-water teleosts distributed broadly in East and Southeast Asia, meet these criteria. Findings Using Oryzias species from 27 local populations, we conducted a simple screening of nonsynonymous SNPs for 11 genes with apparent orthology between medaka and humans. We found medaka SNPs for which the same sites in human orthologs are known to be highly differentiated among the HapMap populations. Importantly, some of these SNPs show signals of positive selection. Conclusion These results indicate that medaka is a promising model system for comparative population genomics exploring the functional and adaptive significance of allelic differentiations.

  9. Magnetic hydroxyapatite: a promising multifunctional platform for nanomedicine application.

    Science.gov (United States)

    Mondal, Sudip; Manivasagan, Panchanathan; Bharathiraja, Subramaniyan; Santha Moorthy, Madhappan; Kim, Hye Hyun; Seo, Hansu; Lee, Kang Dae; Oh, Junghwan

    2017-01-01

    In this review, specific attention is paid to the development of nanostructured magnetic hydroxyapatite (MHAp) and its potential application in controlled drug/gene delivery, tissue engineering, magnetic hyperthermia treatment, and the development of contrast agents for magnetic resonance imaging. Both magnetite and hydroxyapatite materials have excellent prospects in nanomedicine with multifunctional therapeutic approaches. To date, many research articles have focused on biomedical applications of nanomaterials because of which it is very difficult to focus on any particular type of nanomaterial. This study is possibly the first effort to emphasize on the comprehensive assessment of MHAp nanostructures for biomedical applications supported with very recent experimental studies. From basic concepts to the real-life applications, the relevant characteristics of magnetic biomaterials are patented which are briefly discussed. The potential therapeutic and diagnostic ability of MHAp-nanostructured materials make them an ideal platform for future nanomedicine. We hope that this advanced review will provide a better understanding of MHAp and its important features to utilize it as a promising material for multifunctional biomedical applications.

  10. Scientists find promising predictor of HPV-related oropharynx cancer

    Science.gov (United States)

    Researchers have found that antibodies against the human papillomavirus (HPV) may help identify individuals who are at greatly increased risk of HPV-related cancer of the oropharynx, which is a portion of the throat that contains the tonsils.

  11. Hu and Yo antibodies have heterogeneous avidity.

    Science.gov (United States)

    Totland, Cecilie; Aarseth, Jan; Vedeler, Christian

    2007-04-01

    Onconeural antibodies such as anti-Hu and anti-Yo may be important in the pathogenesis of paraneoplastic neurological syndromes. The avidity of these antibodies is not known. In this study, we compared the avidity of Hu and Yo antibodies both at single time points and over a time range of 2 months to 6 years. The avidity of Yo and Hu antibodies differed among the patients, but anti-Yo generally had higher avidity than anti-Hu. Whether Yo antibodies are more pathogenic than Hu antibodies are presently unknown.

  12. Stem cell therapy in spinal cord injury: Hollow promise or promising science?

    Directory of Open Access Journals (Sweden)

    Aimee Goel

    2016-01-01

    Full Text Available Spinal cord injury (SCI remains one of the most physically, psychologically and socially debilitating conditions worldwide. While rehabilitation measures may help limit disability to some extent, there is no effective primary treatment yet available. The efficacy of stem cells as a primary therapeutic option in spinal cord injury is currently an area under much scrutiny and debate. Several laboratory and some primary clinical studies into the use of bone marrow mesenchymal stem cells or embryonic stem cell-derived oligodentrocyte precursor cells have shown some promising results in terms of remyelination and regeneration of damaged spinal nerve tracts. More recently,laboratory and early clinical experiments into the use of Olfactory Ensheathing Cells, a type of glial cell derived from olfactory bulb and mucosa have provided some phenomenal preliminary evidence as to their neuroregenerative and neural bridging capacity. This report compares and evaluates some current research into selected forms of embryonic and mesenchymal stem cell therapy as well as olfactory ensheathing cell therapy in SCI, and also highlights some legal and ethical issues surrounding their use. While early results shows promise, more rigorous large scaleclinical trials are needed to shed light on the safety, efficacy and long term viability of stem cell and cellular transplant techniques in SCI.

  13. Prediction of the Hydrogen Peroxide-Induced Methionine Oxidation Propensity in Monoclonal Antibodies.

    Science.gov (United States)

    Agrawal, Neeraj J; Dykstra, Andrew; Yang, Jane; Yue, Hai; Nguyen, Xichdao; Kolvenbach, Carl; Angell, Nicolas

    2018-01-08

    Methionine oxidation in therapeutic antibodies can impact the product's stability, clinical efficacy, and safety and hence it is desirable to address the methionine oxidation liability during antibody discovery and development phase. Although the current experimental approaches can identify the oxidation-labile methionine residues, their application is limited mostly to the development phase. We demonstrate an in silico method that can be used to predict oxidation-labile residues based solely on the antibody sequence and structure information. Since antibody sequence information is available in the discovery phase, the in silico method can be applied very early on to identify the oxidation-labile methionine residues and subsequently address the oxidation liability. We believe that the in silico method for methionine oxidation liability assessment can aid in antibody discovery and development phase to address the liability in a more rational way. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  14. Nanoparticles camouflaged in platelet membrane coating as an antibody decoy for the treatment of immune thrombocytopenia.

    Science.gov (United States)

    Wei, Xiaoli; Gao, Jie; Fang, Ronnie H; Luk, Brian T; Kroll, Ashley V; Dehaini, Diana; Zhou, Jiarong; Kim, Hyeon Woo; Gao, Weiwei; Lu, Weiyue; Zhang, Liangfang

    2016-12-01

    Immune thrombocytopenia purpura (ITP) is characterized by the production of pathological autoantibodies that cause reduction in platelet counts. The disease can have serious medical consequences, leading to uncontrolled bleeding that can be fatal. Current widely used therapies for the treatment of ITP are non-specific and can, at times, result in complications that are more burdensome than the disease itself. In the present study, the use of platelet membrane-coated nanoparticles (PNPs) as a platform for the specific clearance of anti-platelet antibodies is explored. The nanoparticles, whose outer layer displays the full complement of native platelet surface proteins, act as decoys that strongly bind pathological anti-platelet antibodies in order to minimize disease burden. Here, we study the antibody binding properties of PNPs and assess the ability of the nanoparticles to neutralize antibody activity both in vitro and in vivo. Ultimately, we leverage the neutralization capacity of PNPs to therapeutically treat a murine model of antibody-induced thrombocytopenia and demonstrate considerable efficacy as shown in a bleeding time assay. PNPs represent a promising platform for the specific treatment of antibody-mediated immune thrombocytopenia by acting as an alternative target for anti-platelet antibodies, thus preserving circulating platelets with the potential of leaving broader immune function intact. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Soluble HIV-1 envelope immunogens derived from an elite neutralizer elicit cross-reactive V1V2 antibodies and low potency neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    Sara Carbonetti

    Full Text Available We evaluated four gp140 Envelope protein vaccine immunogens that were derived from an elite neutralizer, subject VC10042, whose plasma was able to potently neutralize a wide array of genetically distinct HIV-1 isolates. We sought to determine whether soluble Envelope proteins derived from the viruses circulating in VC10042 could be used as immunogens to elicit similar neutralizing antibody responses by vaccination. Each gp140 was tested in its trimeric and monomeric forms, and we evaluated two gp140 trimer vaccine regimens in which adjuvant was supplied at all four immunizations or at only the first two immunizations. Interestingly, all four Envelope immunogens elicited high titers of cross-reactive antibodies that recognize the variable regions V1V2 and are potentially similar to antibodies linked with a reduced risk of HIV-1 acquisition in the RV144 vaccine trial. Two of the four immunogens elicited neutralizing antibody responses that neutralized a wide array of HIV-1 isolates from across genetic clades, but those responses were of very low potency. There were no significant differences in the responses elicited by trimers or monomers, nor was there a significant difference between the two adjuvant regimens. Our study identified two promising Envelope immunogens that elicited anti-V1V2 antibodies and broad, but low potency, neutralizing antibody responses.

  16. 9 CFR 113.452 - Erysipelothrix Rhusiopathiae Antibody.

    Science.gov (United States)

    2010-01-01

    ..., DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD... Antibody is a specific antibody product containing antibodies directed against one or more somatic antigens...

  17. Sungkai (Peronema canescens) a promising pioneer tree : an experimental provenance study in Indonesia

    OpenAIRE

    Hatta, G.M.

    1999-01-01

    Sungkai ( Peronema canescens Jack.), Verbenaceae, is one among the fancy woods of Indonesia. Sungkai belongs to a small number of species recommended by The Ministry of Forestry for use in the development of industrial forest plantations (IFP). The IFPs are carried out in response to an increasing wood demand and aim at reducing pressure on the natural forests, thereby contributing to national land conservation objectives, as well as to the supply of industrial r...

  18. Sungkai (Peronema canescens) a promising pioneer tree : an experimental provenance study in Indonesia

    NARCIS (Netherlands)

    Hatta, G.M.

    1999-01-01

    Sungkai ( Peronema canescens Jack.), Verbenaceae, is one among the fancy woods of Indonesia. Sungkai belongs to a small number of species recommended by The Ministry of Forestry for use in the development of industrial forest plantations (IFP). The IFPs are carried out

  19. The self-regulating brain and neurofeedback: Experimental science and clinical promise.

    Science.gov (United States)

    Thibault, Robert T; Lifshitz, Michael; Raz, Amir

    2016-01-01

    Neurofeedback, one of the primary examples of self-regulation, designates a collection of techniques that train the brain and help to improve its function. Since coming on the scene in the 1960s, electroencephalography-neurofeedback has become a treatment vehicle for a host of mental disorders; however, its clinical effectiveness remains controversial. Modern imaging technologies of the living human brain (e.g., real-time functional magnetic resonance imaging) and increasingly rigorous research protocols that utilize such methodologies begin to shed light on the underlying mechanisms that may facilitate more effective clinical applications. In this paper we focus on recent technological advances in the field of human brain imaging and discuss how these modern methods may influence the field of neurofeedback. Toward this end, we outline the state of the evidence and sketch out future directions to further explore the potential merits of this contentious therapeutic prospect. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Monoclonal antibodies to Treponema Pallidum.

    NARCIS (Netherlands)

    H.J.M. van de Donk; J.D.A. van Embden; M.F. van Olderen; A.D.M.E. Osterhaus (Albert); J.C. de Jong (Jan)

    1984-01-01

    textabstractThree successive fusions of mouse myeloma cells and spleen lymphocytes of a mouse immunized with Treponema Pallidum resulted in one hybridoma producing anti T. pallidum antibodies for each fusion. The mice were immunized with live pallidum cells respectively 1, 3 and 5 months before

  1. Antibody-mediated targeting of the transferrin receptor in cancer cells.

    Science.gov (United States)

    Luria-Pérez, Rosendo; Helguera, Gustavo; Rodríguez, José A

    Iron is essential for cell growth and is imported into cells in part through the action of transferrin (Tf), a protein that binds its receptor (TfR1 or CD71) on the surface of a cell, and then releases iron into endosomes. TfR1 is a single pass type-II transmembrane protein expressed at basal levels in most tissues. High expression of TfR1 is typically associated with rapidly proliferating cells, including various types of cancer. TfR1 is targeted by experimental therapeutics for several reasons: its cell surface accessibility, constitutive endocytosis into cells, essential role in cell growth and proliferation, and its overexpression by cancer cells. Among the therapeutic agents used to target TfR1, antibodies stand out due to their remarkable specificity and affinity. Clinical trials are being conducted to evaluate the safety and efficacy of agents targeting TfR1 in cancer patients with promising results. These observations suggest that therapies targeting TfR1 as direct therapeutics or delivery conduits remain an attractive alternative for the treatment of cancers that overexpress the receptor. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  2. Novel anti-HER2 monoclonal antibodies: synergy and antagonism with tumor necrosis factor-α

    Directory of Open Access Journals (Sweden)

    Ceran Ceyhan

    2012-10-01

    Full Text Available Abstract Background One-third of breast cancers display amplifications of the ERBB2 gene encoding the HER2 kinase receptor. Trastuzumab, a humanized antibody directed against an epitope on subdomain IV of the extracellular domain of HER2 is used for therapy of HER2-overexpressing mammary tumors. However, many tumors are either natively resistant or acquire resistance against Trastuzumab. Antibodies directed to different epitopes on the extracellular domain of HER2 are promising candidates for replacement or combinatorial therapy. For example, Pertuzumab that binds to subdomain II of HER2 extracellular domain and inhibits receptor dimerization is under clinical trial. Alternative antibodies directed to novel HER2 epitopes may serve as additional tools for breast cancer therapy. Our aim was to generate novel anti-HER2 monoclonal antibodies inhibiting the growth of breast cancer cells, either alone or in combination with tumor necrosis factor-α (TNF-α. Methods Mice were immunized against SK-BR-3 cells and recombinant HER2 extracellular domain protein to produce monoclonal antibodies. Anti-HER2 antibodies were characterized with breast cancer cell lines using immunofluorescence, flow cytometry, immunoprecipitation, western blot techniques. Antibody epitopes were localized using plasmids encoding recombinant HER2 protein variants. Antibodies, either alone or in combination with TNF-α, were tested for their effects on breast cancer cell proliferation. Results We produced five new anti-HER2 monoclonal antibodies, all directed against conformational epitope or epitopes restricted to the native form of the extracellular domain. When tested alone, some antibodies inhibited modestly but significantly the growth of SK-BR-3, BT-474 and MDA-MB-361 cells displaying ERBB2 amplification. They had no detectable effect on MCF-7 and T47D cells lacking ERBB2 amplification. When tested in combination with TNF-α, antibodies acted synergistically on SK-BR-3 cells

  3. Studies of monoclonal antibodies IOR-CEA-1 and IOR-EGF/R3 labelled with {sup 99m}Tc; Estudo de marcacao dos anticorpos monoclonais IOR-CEA-1 e IOR-EGF/R3 com {sup 99m}Tc

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Carla Roberta de Barros Rodrigues

    2005-07-01

    Nuclear Medicine is a speciality that uses radioisotopes for the diagnosis or treatment of diseases and it is considered one of the best tools among the diagnostic modalities for detection of cancer. {sup 99m}Tc is one of the main isotopes for labelling antibodies and in Nuclear Medicine in general, due to its adequate physical properties, availability and low cost. Labelled monoclonal antibodies have shown promising results for diagnosis and therapy of cancer and their use has brought great experimental and clinical advances in the field of oncology. The main clinical applications of immunoscintigraphy with monoclonal antibodies are staging and evaluation of tumoral reappearance. The antibodies employed in this work were: OIR-CEA-1, a murine monoclonal antibody that acts directly against CEA expressed in several neoplasia in particular those from the gastrointestinal tract (colorectal cancer) and IOR-EGF/R3, a murine monoclonal antibody that binds to the external domain of EGF-R and it has been used in the diagnosis of tumors of epithelial origin. The objectives of this work were the development and optimization of the reduction and purification processes, the radiolabelling techniques and quality control procedures (radiochemical, immunoreactivity and cystein challenge) and imaging studies of monoclonal antibodies OIR-CEA-1 and IOR-EGF/R3, using the simple, fast and efficient method of direct labelling of the antibody with {sup 99m}Tc. The final results was the definition of the best conditions for the preparation of lyophilized reactive kits of OIR-CEA-1 and IOR- EGF/R3 for an efficient diagnostic application in Nuclear Medicine. The most adequate conditions for the labelling of the antibodies were: 1.0 mg Ab, 29 {mu}L MDP, 3.0 {mu}g Sn{sup 2+}, 1 mL of {sup 99m}Tc and 30 min. reaction time. With these conditions the labelling yield was always higher than 95% and the maximum activity of {sup 99m}Tc was about 2220 MBq (60 mCi). The evidences of the efficiency and

  4. Allogeneic major histocompatibility complex-mismatched equine bone marrow-derived mesenchymal stem cells are targeted for death by cytotoxic anti-major histocompatibility complex antibodies.

    Science.gov (United States)

    Berglund, A K; Schnabel, L V

    2017-07-01

    Allogeneic mesenchymal stem cells (MSCs) are a promising cell source for treating musculoskeletal injuries in horses. Controversy exists, however, over whether major histocompatibility complex (MHC)-mismatched MSCs are recognised by the recipient immune system and targeted for death by a cytotoxic antibody response. To determine if cytotoxic anti-MHC antibodies generated in vivo following MHC-mismatched MSC injections are capable of initiating complement-dependent cytotoxicity of MSCs. Experimental controlled study. Antisera previously collected at Days 0, 7, 14 and 21 post-injection from 4 horses injected with donor MHC-mismatched equine leucocyte antigen (ELA)-A2 haplotype MSCs and one control horse injected with donor MHC-matched ELA-A2 MSCs were utilised in this study. Antisera were incubated with ELA-A2 MSCs before adding complement in microcytotoxicity assays and cell death was analysed via eosin dye exclusion. ELA-A2 peripheral blood leucocytes (PBLs) were used in the assays as a positive control. Antisera from all 4 horses injected with MHC-mismatched MSCs contained antibodies that caused the death of ELA-A2 haplotype MSCs in the microcytotoxicity assays. In 2 of the 4 horses, antibodies were present as early as Day 7 post-injection. MSC death was consistently equivalent to that of ELA-A2 haplotype PBL death at all time points and antisera dilutions. Antisera from the control horse that was injected with MHC-matched MSCs did not contain cytotoxic ELA-A2 antibodies at any of the time points examined. This study examined MSC death in vitro only and utilized antisera from a small number of horses. The cytotoxic antibody response induced in recipient horses following injection with donor MHC-mismatched MSCs is capable of killing donor MSCs in vitro. These results suggest that the use of allogeneic MHC-mismatched MSCs must be cautioned against, not only for potential adverse events, but also for reduced therapeutic efficacy due to targeted MSC death. © 2016 The

  5. Monoclonal Antibodies for Systemic Lupus Erythematosus (SLE

    Directory of Open Access Journals (Sweden)

    Gabriella Moroni

    2010-01-01

    Full Text Available A number of monoclonal antibodies (mAb are now under investigation in clinical trials to assess their potential role in Systemic Lupus Erythematosus (SLE. The most frequently used mAb is rituximab, which is directed against CD20, a membrane protein expressed on B lymphocytes. Uncontrolled trials reported an improvement of SLE activity in non-renal patients and other studies even reported an improvement of severe lupus nephritis unresponsive to conventional treatments. However two randomized trials failed to show the superiority of rituximab over conventional treatment in non renal SLE and in lupus nephritis. Preliminary trials reported promising results with epratuzumab, a humanized mAb directed against CD22, and with belimumab, a human mAb that specifically recognizes and inhibits the biological activity of BLyS a cytokine of the tumornecrosis-factor (TNF ligand superfamily. Other clinical trials with mAb directed against TNF-alpha, interleukin-10 (Il-10, Il-6, CD154, CD40 ligand, IL-18 or complement component C5 are under way. At present, however, in spite of good results reported by some studies, no firm conclusion on the risk-benefit profile of these mAbs in patients with SLE can be drawn from the available studies.

  6. High specificity but low sensitivity of mutation-specific antibodies against EGFR mutations in non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Bondgaard, Anna-Louise; Høgdall, Estrid; Mellemgaard, Anders

    2014-01-01

    of more sensitive methods including real-time PCR (RT-PCR). Immunohistochemistry with mutation-specific antibodies might be a promising detection method. We evaluated 210 samples with NSCLC from an unselected Caucasian population. Extracted DNA was analyzed for EGFR mutations by RT-PCR (Therascreen EGFR......, and staining score (multipum of intensity (graded 0-3) and percentages (0-100%) of stained tumor cells) was calculated. Positivity was defined as staining score >0. Specificity of exon19 antibody was 98.8% (95% confidence interval=95.9-99.9%) and of exon21 antibody 97.8% (95% confidence interval=94...... was demonstrated. However, sensitivity was low, especially for exon19 deletions, and thus these antibodies cannot yet be used as screening method for EGFR mutations in NSCLC. Refinement of sensitivity for the mutation-specific antibodies is warranted to improve molecular diagnosis using EGFR immunohistochemistry....

  7. Radioimmunological determination of growth hormone antibodies

    International Nuclear Information System (INIS)

    Kracmar, P.; Hnikova, O.

    1979-01-01

    The method is based on the assumption of the presence of antibodies in the serum of the patient and the formation of the complex antibody-tracer ( 125 I-STH). For separation the principle is used of two antibodies and subsequent ultrafiltration with membrane ultrafilters. Clinical experience, reproducibility and the procedure recommended for simple monitoring and the determination of the amount of antibodies in the serum of patients are presented. (author)

  8. Antibody therapeutics - the evolving patent landscape.

    Science.gov (United States)

    Petering, Jenny; McManamny, Patrick; Honeyman, Jane

    2011-09-01

    The antibody patent landscape has evolved dramatically over the past 30 years, particularly in areas of technology relating to antibody modification to reduce immunogenicity in humans or improve antibody function. In some cases antibody techniques that were developed in the 1980s are still the subject of patent protection in the United States or Canada. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. 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 resp...... against the infection. On the other hand, immune complexes between the beta-lactamase and corresponding antibodies could play a role in the pathogenesis of bronchopulmonary injury in CF by mediating hyperimmune reactions....

  10. Characterisation of new monoclonal antibodies reacting with prions from both human and animal brain tissues

    DEFF Research Database (Denmark)

    Cordes, H.; Bergstrom, A.L.; Ohm, J.

    2008-01-01

    Post-mortem diagnosis of transmissible spongiform encephalopathies (prion diseases) is primarily based on the detection of a protease resistant, misfolded disease associated isoform (PrP(Sc)) of the prion protein (PrP(C)) on neuronal cells. These methods depend on antibodies directed against Pr...... spongiform encephalopathy (bovine brain), scrapie (ovine brain) and experimental scrapie in hamster and in mice. The antibodies were also used for PET-blotting in which PrP(Sc) blotted from brain tissue sections onto a nitrocellulose membrane is visualized with antibodies after protease and denaturant...

  11. Binding induced conformational changes of proteins correlate with their intrinsic fluctuations: a case study of antibodies

    Directory of Open Access Journals (Sweden)

    Keskin Ozlem

    2007-05-01

    Full Text Available Abstract Background How antibodies recognize and bind to antigens can not be totally explained by rigid shape and electrostatic complimentarity models. Alternatively, pre-existing equilibrium hypothesis states that the native state of an antibody is not defined by a single rigid conformation but instead with an ensemble of similar conformations that co-exist at equilibrium. Antigens bind to one of the preferred conformations making this conformation more abundant shifting the equilibrium. Results Here, two antibodies, a germline antibody of 36–65 Fab and a monoclonal antibody, SPE7 are studied in detail to elucidate the mechanism of antibody-antigen recognition and to understand how a single antibody recognizes different antigens. An elastic network model, Anisotropic Network Model (ANM is used in the calculations. Pre-existing equilibrium is not restricted to apply to antibodies. Intrinsic fluctuations of eight proteins, from different classes of proteins, such as enzymes, binding and transport proteins are investigated to test the suitability of the method. The intrinsic fluctuations are compared with the experimentally observed ligand induced conformational changes of these proteins. The results show that the intrinsic fluctuations obtained by theoretical methods correlate with structural changes observed when a ligand is bound to the protein. The decomposition of the total fluctuations serves to identify the different individual modes of motion, ranging from the most cooperative ones involving the overall structure, to the most localized ones. Conclusion Results suggest that the pre-equilibrium concept holds for antibodies and the promiscuity of antibodies can also be explained this hypothesis: a limited number of conformational states driven by intrinsic motions of an antibody might be adequate to bind to different antigens.

  12. Affinity improvement of a therapeutic antibody by structure-based computational design: generation of electrostatic interactions in the transition state stabilizes the antibody-antigen complex.

    Directory of Open Access Journals (Sweden)

    Masato Kiyoshi

    Full Text Available The optimization of antibodies is a desirable goal towards the development of better therapeutic strategies. The antibody 11K2 was previously developed as a therapeutic tool for inflammatory diseases, and displays very high affinity (4.6 pM for its antigen the chemokine MCP-1 (monocyte chemo-attractant protein-1. We have employed a virtual library of mutations of 11K2 to identify antibody variants of potentially higher affinity, and to establish benchmarks in the engineering of a mature therapeutic antibody. The most promising candidates identified in the virtual screening were examined by surface plasmon resonance to validate the computational predictions, and to characterize their binding affinity and key thermodynamic properties in detail. Only mutations in the light-chain of the antibody are effective at enhancing its affinity for the antigen in vitro, suggesting that the interaction surface of the heavy-chain (dominated by the hot-spot residue Phe101 is not amenable to optimization. The single-mutation with the highest affinity is L-N31R (4.6-fold higher affinity than wild-type antibody. Importantly, all the single-mutations showing increase affinity incorporate a charged residue (Arg, Asp, or Glu. The characterization of the relevant thermodynamic parameters clarifies the energetic mechanism. Essentially, the formation of new electrostatic interactions early in the binding reaction coordinate (transition state or earlier benefits the durability of the antibody-antigen complex. The combination of in silico calculations and thermodynamic analysis is an effective strategy to improve the affinity of a matured therapeutic antibody.

  13. 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

  14. Antibodies Against Melanin | Wassermann | South African Medical ...

    African Journals Online (AJOL)

    This study reports on unsuccessful attempts to produce antibodies against melanoprotein in rabbits. Available evidence suggests antibodies against melanocytes in the aetiology of vitiligo, but there is no convincing evidence for antibodies against melanin per se. It is suggested that the demonstration of antibodif's against ...

  15. In vitro and in vivo studies evaluating antisemen antibodies as a potential spermicidal agent in hamsters.

    Science.gov (United States)

    Chen, De-Yu; Liu, Li-Min; Xie, Qing-Dong; Xu, Lan; Huang, Tian-Hua

    2009-09-01

    To determine the spermicidal activity of antisemen antibodies in the hamster model. Prospective, controlled study. Advanced preclinical sciences center. Subgroups of 10 and 14 golden hamsters. Ex vitro and in vivo treatment of sperm with antisemen antibodies or normal rabbit serum. The EC(50) value of antisemen antibodies, the time required for 50% motility loss of progressively motile spermatozoa exposed to antisemen antibodies, the average sperm mitochondrion fluorescence intensity, the rate of fertilization, and the scoring of histologic changes in the hamster vaginal tissue. The EC(50) value of antisemen antibodies was found 70 microg/mL, and the time required for 50% motility loss of progressively motile spermatozoa exposed to antisemen antibodies (at 70 microg/mL) was 5 minutes; for the experimental and control groups, the average fluorescence intensities of sperm mitochondria were respectively 180.28 +/- 82.24 and 309.74 +/- 148.37, the fertilization rates in vitro were 0.09% and 45%, the rates of fertilization with intrauterine sperm injection were 0 and 15.0%. There was a significant difference between two groups. None of the four hamsters that received antisemen antibodies in gel-polyoxyl-40-stearate had epithelial disruption characteristic of inflammation. Antisemen antibodies possess appreciable spermicidal potential, which may be explored as an effective constituent of spermicide.

  16. Detection of antibodies to co-trimoxazole (preservative drug interfering with routine red cell antibody screening

    Directory of Open Access Journals (Sweden)

    Deepti Sachan

    2018-01-01

    Full Text Available Drug-dependent antibodies can rarely cause interference in pretransfusion antibody screening. The diluents for commercial reagent red blood cells contain different antibiotics, such as chloramphenicol, neomycin sulfate, and gentamycin as a preservative. The presence of antibodies to a given drug in patient may lead to positive results when performing antibody identification. We present a rare case of detection of anti-co-trimoxazole antibody during routine antibody screening in a female patient undergoing neurosurgery. These antibodies mimicked as antibody against high-frequency red cell antigens reacting in both saline phase as well as antiglobulin phase. Anti-co-trimoxazole antibody was confirmed by repeating antibody screen using reagent red cells of different manufacturers with and without co-trimoxazole drug as preservative as well as using washed red cell panels. There were no associated clinical or laboratory evidence of hemolysis.

  17. Vaccination, squalene and anti-squalene antibodies: facts or fiction?

    Science.gov (United States)

    Lippi, Giuseppe; Targher, Giovanni; Franchini, Massimo

    2010-04-01

    Squalene, a hydrocarbon obtained for commercial purposes primarily from shark liver oil and other botanic sources, is increasingly used as an immunologic adjuvant in several vaccines, including seasonal and the novel influenza A (H1N1) 2009 pandemic flu vaccines. Nearly a decade ago, squalene was supposed to be the experimental anthrax vaccine ingredient that caused the onset of Persian Gulf War syndrome in many veterans, since antibodies to squalene were detected in the blood of most patients affected by this syndrome. This evidence has raised a widespread concern about the safety of squalene containing adjuvants (especially MF59) of influenza vaccines. Nevertheless, further clinical evidence clearly suggested that squalene is poorly immunogenic, that low titres of antibodies to squalene can be also detected in sera from healthy individuals, and that neither the presence of anti-squalene antibodies nor their titre is significantly increased by immunization with vaccines containing squalene (or MF59) as an adjuvant. This review summarizes the current scientific evidence about the relationship between squalene, anti-squalene antibodies and vaccination. Copyright 2009 Elsevier B.V. All rights reserved.

  18. Antibody trapping: A novel mechanism of parasite immune evasion by the trematode Echinostoma caproni.

    Directory of Open Access Journals (Sweden)

    Alba Cortés

    2017-07-01

    Full Text Available Helminth infections are among the most prevalent neglected tropical diseases, causing an enormous impact in global health and the socioeconomic growth of developing countries. In this context, the study of helminth biology, with emphasis on host-parasite interactions, appears as a promising approach for developing new tools to prevent and control these infections.The role that antibody responses have on helminth infections is still not well understood. To go in depth into this issue, work on the intestinal helminth Echinostoma caproni (Trematoda: Echinostomatidae has been undertaken. Adult parasites were recovered from infected mice and cultured in vitro. Double indirect immunofluorescence at increasing culture times was done to show that in vivo-bound surface antibodies become trapped within a layer of excretory/secretory products that covers the parasite. Entrapped antibodies are then degraded by parasite-derived proteases, since protease inhibitors prevent for antibody loss in culture. Electron microscopy and immunogold-labelling of secreted proteins provide evidence that this mechanism is consistent with tegument dynamics and ultrastructure, hence it is feasible to occur in vivo. Secretory vesicles discharge their content to the outside and released products are deposited over the parasite surface enabling antibody trapping.At the site of infection, both parasite secretion and antibody binding occur simultaneously and constantly. The continuous entrapment of bound antibodies with newly secreted products may serve to minimize the deleterious effects of the antibody-mediated attack. This mechanism of immune evasion may aid to understand the limited effect that antibody responses have in helminth infections, and may contribute to the basis for vaccine development against these highly prevalent diseases.

  19. Adsorption orientations and immunological recognition of antibodies on graphene

    Science.gov (United States)

    Vilhena, J. G.; Dumitru, A. C.; Herruzo, Elena T.; Mendieta-Moreno, Jesús I.; Garcia, Ricardo; Serena, P. A.; Pérez, Rubén

    2016-07-01

    MD results and the AFM images demonstrate that the IgG antibodies are strongly adsorbed, do not unfold, and retain their secondary and tertiary structures upon deposition. Statistical analysis of the AFM images shows that many of the antibodies adopt vertical orientations, even at very small coverages, which expose at least one Fab binding site for recognition events. Single molecule force spectroscopy experiments demonstrate the immunological response of the deposited antibodies by recognizing its specific antigens. The above properties together with the strong anchoring and preservation of the secondary structure, make graphene an excellent candidate for the development of immunosensors. Electronic supplementary information (ESI) available: Further details concerning the experimental methods, the MD simulation protocols, and the characterization and stability of the different adsorption configurations. See DOI: 10.1039/C5NR07612A

  20. Indium antimonide nanowires arrays for promising thermoelectric converters

    Directory of Open Access Journals (Sweden)

    Gorokh G. G.

    2015-02-01

    Full Text Available The authors have theoretically substantiated the possibility to create promising thermoelectric converters based on quantum wires. The calculations have shown that the use of quantum wires with lateral dimensions smaller than quantum confinement values and high concentration and mobility of electrons, can lead to a substantial cooling of one of the contacts up to tens of degrees and to the heating of the other. The technological methods of manufacturing of indium antimonide nanowires arrays with high aspect ratio of the nanowire diameters to their length in the modified nanoporous anodic alumina matrixes were developed and tested. The microstructure and composition of the formed nanostructures were investigated. The electron microscopy allowed establishing that within each pore nanowires are formed with diameters of 35 nm and a length of 35 microns (equal to the matrix thickness. The electron probe x-ray microanalysis has shown that the atomic ratio of indium and antimony in the semiconductor nanostructures amounted to 38,26% and 61,74%, respectively. The current-voltage measurement between the upper and lower contacts of Cu/InSb/Cu structure (1 mm2 has shown that at 2.82 V negative voltage at the emitter contact, current density is 129,8 A/cм2, and the collector contact is heated up to 75 degrees during 150 sec. Thus, the experimental results confirmed the theoretical findings that the quantum wire systems can be used to create thermoelectric devices, which can be widely applied in electronics, in particular, for cooling integrated circuits (processors, thermal controlling of the electrical circuits by changing voltage value.

  1. 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

  2. Production of Monoclonal Antibody against Human Nestin

    OpenAIRE

    Hadavi, Reza; Zarnani, Amir Hassan; Ahmadvand, Negah; Mahmoudi, Ahmad Reza; Bayat, Ali Ahmad; Mahmoudian, Jafar; Sadeghi, Mohammad-Reza; Soltanghoraee, Haleh; Akhondi, Mohammad Mehdi; Tarahomi, Majid; Jeddi-Tehrani, Mahmood; Rabbani, Hodjattallah

    2010-01-01

    We have employed a peptide-based antibody generation protocol for producing antibody against human nestin. Using a 12-mer synthetic peptide from repetitive region of human nestin protein devoid of any N- or O-glyco-sylation sequences, we generated a mouse monoclonal antibody capable of recognizing human, mouse, bovine, and rat nestin. A wide variety of nestin proteins ranging from 140?250 kDa was detected by this antibody. This antibody is highly specific and functional in applications such a...

  3. Serum Antibody Biomarkers for ASD

    Science.gov (United States)

    2015-10-01

    45-56. Singh VK. (2009) Phenotypic expression of autoimmune autistic disorder (AAD): A major subset of autism. Ann Clin Psychiat. 21:148-160. 5...spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in communication (verbal and nonverbal), social interactions, and... autoimmunity ; in particular, the generation of antibodies reactive against brain and CNS proteins. The goal of this grant is to identify serum

  4. 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

  5. The pragmatics of NPP presidential campaign promises in Ghana's ...

    African Journals Online (AJOL)

    The paper discusses election campaign promises under Commissives, an aspect of Speech Act Theory, and Political Discourse Analysis (PDA). It considers the importance of context and looks at the social settings that are connected with promises. It examines the semantics, pragmatics and the structure of campaign ...

  6. Nanocellular polymer foams as promising high performance thermal insulation materials

    NARCIS (Netherlands)

    Liu, Shanqiu; Duvigneau, Joost; Vancso, Gyula J.

    2015-01-01

    Low density, nanocellular polymer nanocomposite foams are considered as a promising new class of materials with many promising applications, for example to passively enhance the energy efficiency of buildings. This paper discusses recent developments in this field of polymer materials science.

  7. Local and global trust based on the concept of promises

    NARCIS (Netherlands)

    Bergstra, J.; Burgess, M.

    2009-01-01

    We use the notion of a promise to define local trust between agents possessing autonomous decision-making. An agent is trustworthy if it is expected that it will keep a promise. This definition satisfies most commonplace meanings of trust. Reputation is then an estimation of this expectation value

  8. Clonal relationships between thyroid-stimulating hormone receptor-stimulating antibodies illustrate the effect of hypermutation on antibody function

    DEFF Research Database (Denmark)

    Padoa, Carolyn J; Larsen, Sanne L; Hampe, Christiane S

    2009-01-01

    Summary Graves' disease is characterized by production of agonist antibodies to the thyroid-stimulating hormone receptor (TSHR), but knowledge of the genetic and somatic events leading to their aberrant production is limited. We describe the genetic analysis of two monoclonal antibodies (mAbs) wi......, in experimentally immunized mice, multiple pathogenic antibodies to TSHR can arise from a single clone by a series of somatic mutations in the V-region genes and may give an insight into how such antibodies develop spontaneously in autoimmune Graves' disease....... relationship and derivation from a single precursor B-cell clone. The IGHV-region genes of the two mAbs underwent high degrees of somatic hypermutation by sharing numerous mutations before diverging, while the IGLV genes evolved separately. Interestingly, the mutations were present in both the complementarity...... that the chimeras retained TSAb activities, confirming the close functional relatedness of the V-region genes. Importantly, the IGLV genes in chimeric rFabs had a dominant stimulatory effect at low concentrations, while the IGHV genes had a dominant effect at higher concentrations. Our findings demonstrate that...

  9. Regulation of levels of serum antibodies to ryegrass pollen allergen Lol pIV by an internal image anti-idiotypic monoclonal antibody.

    Science.gov (United States)

    Zhou, E M; Kisil, F T

    1995-03-01

    A murine monoclonal anti-idiotypic antibody (anti-Id), designated B1/1, was produced against an idiotope of a murine antibody (mAb91), which recognizes the epitope, site A, of allergen Lol pIV, one of the major groups of allergens in ryegrass (Lolium perenne) pollen. The ability of B1/1 to modulate the antibody responses to Lol pIV was investigated in murine model systems. In the first system, B1/1-keyhole limpet haemocyanin (KLH) conjugate was administered to treat three different strains of mice (C57BL/6, BALB/c and C3H). In the second and third model systems, a solution of B1/1 in phosphate-buffered saline (PBS) was used to treat syngeneic BALB/c mice at various doses and time intervals, respectively. The treatment with either form of B1/1, administered at doses ranging from 100 ng to 100 micrograms mouse, resulted in a reduction of the levels of the antibodies to Lol pIV. In particular, the level of IgE antibodies to Lol pIV was greatly reduced. The administration of a single intravenous (i.v.) injection of a solution of B1/1 8 weeks prior to the challenge with Lol pIV was still effective in reducing the level of antibodies to the allergen. Moreover, the level of antibodies to Lol pIV that expressed the idiotope mAb91 was also markedly decreased. By contrast, it was observed that the level of antibodies to Lol pIV in mice pretreated with B1/1 in PBS at a dose of 10 ng/mouse increased (albeit slightly) compared to that in mice treated with control mAb. These experimental models lend themselves for investigating the mechanism(s) by which an anti-Id modulates antibody responses to a grass pollen allergen.

  10. Non-infectious aggregates of the prion protein react with several PrPSc-directed antibodies.

    Science.gov (United States)

    Biasini, Emiliano; Seegulam, M Esa; Patti, Brianna N; Solforosi, Laura; Medrano, Andrea Z; Christensen, Heather M; Senatore, Assunta; Chiesa, Roberto; Williamson, R Anthony; Harris, David A

    2008-06-01

    The key event in the pathogenesis of prion diseases is the conformational conversion of the normal prion protein (PrP) (PrP(C)) into an infectious, aggregated isoform (PrP(Sc)) that has a high content of beta-sheet. Historically, a great deal of effort has been devoted to developing antibodies that specifically recognize PrP(Sc) but not PrP(C), as such antibodies would have enormous diagnostic and experimental value. A mouse monoclonal IgM antibody (designated 15B3) and three PrP motif-grafted monoclonal antibodies (referred to as IgG 19-33, 89-112, and 136-158) have been previously reported to react specifically with infectious PrP(Sc) but not PrP(C). In this study, we extend the characterization of these four antibodies by testing their ability to immunoprecipitate and immunostain infectious and non-infectious aggregates of wild-type, mutant, and recombinant PrP. We find that 15B3 as well as the motif-grafted antibodies recognize multiple types of aggregated PrP, both infectious and non-infectious, including forms found in brain, in transfected cells, and induced in vitro from purified recombinant protein. These antibodies are exquisitely selective for aggregated PrP, and do not react with soluble PrP even when present in vast excess. Our results suggest that 15B3 and the motif-grafted antibodies recognize structural features common to both infectious and non-infectious aggregates of PrP. Our study extends the utility of these antibodies for diagnostic and experimental purposes, and it provides new insight into the structural changes that accompany PrP oligomerization and prion propagation.

  11. Immunosympathectomy as the first phenotypic knockout with antibodies.

    Science.gov (United States)

    Cattaneo, Antonino

    2013-03-26

    In a PNAS Classic Article published in 1960, Rita Levi-Montalcini offered formal and conclusive proof that endogenous NGF was responsible for the survival of sympathetic neurons in vivo. Thus ended an experimental tour de force lasting a decade, starting with the demonstration that a humoral factor, produced from a tumor transplanted in a chicken embryo, was responsible for stimulating outgrowth of nerve fibers from sympathetic and sensory neurons. From a more general methodological point of view, this work provided a breakthrough in the quest to achieve targeted loss of function and experimentally validate the function of biological molecules. Finally, this work provided an example of the ablation of a specific neuronal subpopulation in an otherwise intact nervous system, an immunological knife of unsurpassed effectiveness and precision. The novelty and the importance of the PNAS Classic Article is discussed here, collocating it within the context of the particular moment of the NGF discovery saga, of Rita Levi-Montalcini's scientific and academic career, and of the general scientific context of those years. This seminal work, involving the use of antibodies for phenotypic knockout in vivo, planted seeds that were to bear new fruit many years later with the advent of monoclonal antibodies and recombinant antibody technologies.

  12. Mapping the AAV capsid host antibody response towards the development of second generation gene delivery vectors

    Directory of Open Access Journals (Sweden)

    Yu-Shan eTseng

    2014-01-01

    Full Text Available The recombinant Adeno-associated virus (rAAV gene delivery system is entering a crucial and exciting phase with the promise of more than 20 years of intense research now realized in a number of successful human clinical trials. However, as a natural host to AAV infection, anti-AAV antibodies are prevalent in the human population. For example, ~70% of human sera samples are positive for AAV serotype 2 (AAV2. Furthermore, low levels of pre-existing neutralizing antibodies in the circulation are detrimental to the efficacy of corrective therapeutic AAV gene delivery. A key component to overcoming this obstacle is the identification of regions of the AAV capsid that participate in interactions with host immunity, especially neutralizing antibodies, to be modified for neutralization escape. Three main approaches have been utilized to map antigenic epitopes on AAV capsids. The first is directed evolution in which AAV variants are selected in the presence of monoclonal antibodies or pooled human sera. This results in AAV variants with mutations on important neutralizing epitopes. The second is epitope searching, achieved by peptide scanning, peptide insertion or site-directed mutagenesis. The third, a structure biology-based approach, utilizes cryo-electron microscopy and image reconstruction of AAV capsids complexed to fragment antibodies, which are generated from monoclonal antibodies, to directly visualize the epitopes. In this review, the contribution of these three approaches to the current knowledge of AAV epitopes and success in their use to create second generation vectors will be discussed.

  13. Monoclonal antibody fragment from combinatorial phage display library neutralizes alpha-latrotoxin activity and abolishes black widow spider venom lethality, in mice.

    Science.gov (United States)

    Bugli, Francesca; Graffeo, Rosalia; Paroni Sterbini, Francesco; Torelli, Riccardo; Masucci, Luca; Sali, Michela; Grasso, Alfonso; Rufini, Stefano; Ricci, Enzo; Fadda, Giovanni; Pescatori, Mario

    2008-03-15

    Alpha-latrotoxin (alpha-ltx), a component of the venom of black widow spiders (BWSV), binds to higher vertebrates presynaptic nerve terminals, stimulating massive neurotransmitter release. This neurotoxic protein is responsible for most of the symptoms elicited in men by the bite of black widow spider (BWS), i.e. a neurological syndrome named latrodectism. By reasoning that targeting this single component would abrogate most of the effect of BWS envenomation, we took advantage of the antibody phage display technology to generate monoclonal Fab fragments able to bind and neutralize the alpha-ltx. To this aim, we immunized Balb/c mice with purified toxin and cloned their antibody repertoire in the pCombIII phage display vector. By combining a high-stringency affinity selection with a sensitive 45Ca(2+) uptake assay, we isolated a Fab fragment (FM1) able to bind the alpha-ltx in the low nM range and neutralize its ionophore activity, in vitro and in vivo. After the onset of overt symptomatology, administration of FM1 to experimentally envenomed mice induced remission of symptoms and prevented lethality. Since alpha-ltx is the only molecule responsible for the great toxicity of BWS bites in mammals, the FM1 Fab, highly effective in neutralizing the toxin in vivo, represents a promising immunotherapy reagent for treating latrodectic patients.

  14. Vaccination of horses with Lyme vaccines for dogs induces short-lasting antibody responses.

    Science.gov (United States)

    Guarino, Cassandra; Asbie, Sanda; Rohde, Jennifer; Glaser, Amy; Wagner, Bettina

    2017-07-24

    Borrelia burgdorferi can induce Lyme disease. Approved Lyme vaccines for horses are currently not available. In an effort to protect horses, veterinarians are using Lyme vaccines licensed for dogs. However, data to assess the response of horses to, or determine the efficacy of this off-label vaccine use are missing. Here, antibodies against outer surface protein A (OspA), OspC, and OspF were quantified in diagnostic serum submissions from horses with a history of vaccination with canine Lyme vaccines. The results suggested that many horses respond with low and often short-lasting antibody responses. Subsequently, four experimental vaccination trials were performed. First, we investigated antibody responses to three canine vaccines in B. burgdorferi-naïve horses. One killed bacterin vaccine induced antibodies against OspC. OspA antibodies were low for all three vaccines and lasted less than 16weeks. The second trial tested the impact of the vaccine dose using the OspA/OspC inducing bacterin vaccine in horses. A 2mL dose produced higher OspA and OspC antibody values than a 1mL dose. However, the antibody response again quickly declined, independent of dose. Third, the horses were vaccinated with 2 doses of a recombinant OspA vaccine. Previous vaccination and/or environmental exposure enhanced the magnitude and longevity of the OspA antibody response to about 20weeks. Last, the influence of intramuscular versus subcutaneous vaccine administration was investigated for the recombinant OspA vaccine. OspA antibody responses were not influenced by injection route. The current work highlights that commercial Lyme vaccines for dogs induce only transient antibody responses in horses which can also be of low magnitude. Protection from infection with B. burgdorferi should not be automatically assumed after vaccinating horses with Lyme vaccines for dogs. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  15. Establishing an ISO 10001-based promise in inpatients care.

    Science.gov (United States)

    Khan, Mohammad Ashiqur Rahman; Karapetrovic, Stanislav

    2015-01-01

    The purpose of this paper is to explore ISO 10001:2007 in planning, designing and developing a customer satisfaction promise (CSP) intended for inpatients care. Through meetings and interviews with research participants, who included a program manager, unit managers and registered nurses, information about potential promises and their implementation was obtained and analyzed. A number of promises were drafted and one was finally selected to be developed as a CSP. Applying the standard required adaptation and novel interpretation. Additionally, ISO 10002:2004 (Clause 7) was used to design the feedback handling activities. A promise initially chosen for development turned out to be difficult to implement, experience that helped in selecting and developing the final promise. Research participants found the ISO 10001-based method useful and comprehensible. This paper presents a specific health care example of how to adapt a standard's guideline in establishing customer promises. The authors show how a promise can be used in alleviating an existing issue (i.e. communication between carers and patients). The learning can be beneficial in various health care settings. To the knowledge, this paper shows the first example of applying ISO 10001:2007 in a health care case. A few activities suggested by the standard are further detailed, and a new activity is introduced. The integrated use of ISO 10001:2007 and 10002:2004 is presented and how one can be "augmented" by the other is demonstrated.

  16. New High Affinity Monoclonal Antibodies Recognize Non-Overlapping Epitopes On Mesothelin For Monitoring And Treating Mesothelioma

    Science.gov (United States)

    Zhang, Yi-Fan; Phung, Yen; Gao, Wei; Kawa, Seiji; Hassan, Raffit; Pastan, Ira; Ho, Mitchell

    2015-01-01

    Mesothelin is an emerging cell surface target in mesothelioma and other solid tumors. Most antibody drug candidates recognize highly immunogenic Region I (296–390) on mesothelin. Here, we report a group of high-affinity non-Region I rabbit monoclonal antibodies. These antibodies do not compete for mesothelin binding with the immunotoxin SS1P that binds Region I of mesothelin. One pair of antibodies (YP218 and YP223) is suitable to detect soluble mesothelin in a sandwich ELISA with high sensitivity. The new assay can also be used to measure serum mesothelin concentration in mesothelioma patients, indicating its potential use for monitoring patients treated with current antibody therapies targeting Region I. The antibodies are highly specific and sensitive in immunostaining of mesothelioma. To explore their use in tumor therapy, we have generated the immunotoxins based on the Fv of these antibodies. One immunotoxin (YP218 Fv-PE38) exhibits potent anti-tumor cytotoxicity towards primary mesothelioma cell lines in vitro and an NCI-H226 xenograft tumor in mice. Furthermore, we have engineered a humanized YP218 Fv that retains full binding affinity for mesothelin-expressing cancer cells. In conclusion, with their unique binding properties, these antibodies may be promising candidates for monitoring and treating mesothelioma and other mesothelin-expressing cancers. PMID:25996440

  17. Clinical utility of anti-p53 auto-antibody: systematic review and focus on colorectal cancer.

    Science.gov (United States)

    Suppiah, Aravind; Greenman, John

    2013-08-07

    Mutation of the p53 gene is a key event in the carcinogenesis of many different types of tumours. These can occur throughout the length of the p53 gene. Anti-p53 auto-antibodies are commonly produced in response to these p53 mutations. This review firstly describes the various mechanisms of p53 dysfunction and their association with subsequent carcinogenesis. Following this, the mechanisms of induction of anti-p53 auto-antibody production are shown, with various hypotheses for the discrepancies between the presence of p53 mutation and the presence/absence of anti-p53 auto-antibodies. A systematic review was performed with a descriptive summary of key findings of each anti-p53 auto-antibody study in all cancers published in the last 30 years. Using this, the cumulative frequency of anti-p53 auto-antibody in each cancer type is calculated and then compared with the incidence of p53 mutation in each cancer to provide the largest sample calculation and correlation between mutation and anti-p53 auto-antibody published to date. Finally, the review focuses on the data of anti-p53 auto-antibody in colorectal cancer studies, and discusses future strategies including the potentially promising role using anti-p53 auto-antibody presence in screening and surveillance.

  18. 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.

  19. Cold Atmospheric Plasma: A Promising Complementary Therapy for Squamous Head and Neck Cancer.

    Directory of Open Access Journals (Sweden)

    Christian Welz

    Full Text Available Head and neck squamous cell cancer (HNSCC is the 7th most common cancer worldwide. Despite the development of new therapeutic agents such as monoclonal antibodies, prognosis did not change for the last decades. Cold atmospheric plasma (CAP presents the most promising new technology in cancer treatment. In this study the efficacy of a surface micro discharging (SMD plasma device against two head and neck cancer cell lines was proved. Effects on the cell viability, DNA fragmentation and apoptosis induction were evaluated with the MTT assay, alkaline microgel electrophoresis (comet assay and Annexin-V/PI staining. MTT assay revealed that the CAP treatment markedly decreases the cell viability for all tested treatment times (30, 60, 90, 120 and 180 s. IC 50 was reached within maximal 120 seconds of CAP treatment. Comet assay analysis showed a dose dependent high DNA fragmentation being one of the key players in anti-cancer activity of CAP. Annexin-V/PI staining revealed induction of apoptosis in CAP treated HNSCC cell lines but no significant dose dependency was seen. Thus, we confirmed that SMD Plasma technology is definitely a promising new approach on cancer treatment.

  20. Aptamers as a promising approach for the control of parasitic diseases

    Directory of Open Access Journals (Sweden)

    Juan David Ospina-Villa

    2016-11-01

    Full Text Available Aptamers are short single-stranded RNA or DNA oligonucleotides that are capable of binding various biological targets with high affinity and specificity. Their identification initially relies on a molecular process named SELEX (Systematic Evolution of Ligands by EXponential enrichment that has been later modified in order to improve aptamer sensitivity, minimize duration and cost of the assay, as well as increase target types. Several biochemical modifications can help to enhance aptamer stability without affecting significantly target interaction. As a result, aptamers have generated a large interest as promising tools to compete with monoclonal antibodies for detection and inhibition of specific markers of human diseases. One aptamer-based drug is currently authorized and several others are being clinically evaluated. Despite advances in the knowledge of parasite biology and host–parasite interactions from “omics” data, protozoan parasites still affect millions of people around the world and there is an urgent need for drug target discovery and novel therapeutic concepts. In this context, aptamers represent promising tools for pathogen identification and control. Recent studies have reported the identification of “aptasensors” for parasite diagnosis, and “intramers” targeting intracellular proteins. Here we discuss various strategies that have been employed for intracellular expression of aptamers and expansion of their possible application, and propose that they may be suitable for the clinical use of aptamers in parasitic infections.

  1. Natural Killer Cell-Based Cancer Immunotherapies: From Immune Evasion to Promising Targeted Cellular Therapies

    Directory of Open Access Journals (Sweden)

    Erhard Hofer

    2017-07-01

    Full Text Available Immunotherapies based on natural killer (NK cells are among the most promising therapies under development for the treatment of so far incurable forms of leukemia and other types of cancer. The importance of NK cells for the control of viral infections and cancer is supported among others by the findings that viruses and tumors use a multitude of mechanisms to subvert and evade the NK cell system. Infections and malignant diseases can further lead to the shaping of NK cell populations with altered reactivity. Counter measures of potential therapeutic impact include the blocking of inhibitory interactions between NK cell receptors and their cellular ligands, the enhancement of activating receptor signals, and the infusion of large numbers of ex vivo generated and selected NK cells. Moreover, the specific cross-linking of NK cells to their target cells using chimeric antigen receptors or therapeutic bi-/trispecific antibody reagents is a promising approach. In this context, NK cells stand out by their positive effects and safety demonstrated in most clinical trials so far. Based in part on results of the recent EC-sponsored project “NATURIMMUN” and considering additional published work in the field, we discuss below new developments and future directions that have the potential to further advance and establish NK cell-based therapies at the clinics on a broader scale.

  2. Natural Killer Cell-Based Cancer Immunotherapies: From Immune Evasion to Promising Targeted Cellular Therapies.

    Science.gov (United States)

    Hofer, Erhard; Koehl, Ulrike

    2017-01-01

    Immunotherapies based on natural killer (NK) cells are among the most promising therapies under development for the treatment of so far incurable forms of leukemia and other types of cancer. The importance of NK cells for the control of viral infections and cancer is supported among others by the findings that viruses and tumors use a multitude of mechanisms to subvert and evade the NK cell system. Infections and malignant diseases can further lead to the shaping of NK cell populations with altered reactivity. Counter measures of potential therapeutic impact include the blocking of inhibitory interactions between NK cell receptors and their cellular ligands, the enhancement of activating receptor signals, and the infusion of large numbers of ex vivo generated and selected NK cells. Moreover, the specific cross-linking of NK cells to their target cells using chimeric antigen receptors or therapeutic bi-/trispecific antibody reagents is a promising approach. In this context, NK cells stand out by their positive effects and safety demonstrated in most clinical trials so far. Based in part on results of the recent EC-sponsored project "NATURIMMUN" and considering additional published work in the field, we discuss below new developments and future directions that have the potential to further advance and establish NK cell-based therapies at the clinics on a broader scale.

  3. Production of biological reagents for radioimmunoassay second antibody

    International Nuclear Information System (INIS)

    Borghi, V.C.; Silva, S.R. da; Bellini, M.H.; Lin, L.H.

    1992-02-01

    The experimental production of second antibody to be used in hormonal assays, in which the first antibody is raised in rabbits, is described. Four sheep were immunized with the rabbit immunoglobulin prepared at IPEN-CNEN laboratory. Their antisera were evaluated by the human thyrotropin radioimmunoassay employing materials provided by the National Hormone and Pituitary Program (USA), in comparison with a reference antiserum of known quality, produced in goat by the Radioassay Systems Laboratories - RSL (USA). From the fourth booster injection the animals developed antiserum with titer similar to that exhibited by the commercial product, even presenting higher values. These antisera are now being examinated for the optimal conditions of precipitation before be packed for future use and distribution. (author)

  4. Correlated effects of selection for immunity in White Leghorn chicken lines on natural antibodies and specific antibody responses to KLH and M. butyricum

    NARCIS (Netherlands)

    Minozzi, G.; Parmentier, H.K.; Mignon-Grasteau, S.; Nieuwland, M.G.B.; Bed'hom, B.; Gourichon, D.; Minvielle, F.; Pinard-van der Laan, M.H.

    2008-01-01

    Background - The effect of selection for three general immune response traits on primary antibody responses (Ab) to Mycobacterium butyricum or keyhole limpet hemocyanin (KLH) was studied in four experimental lines of White Leghorn chicken. Birds underwent 12 generations of selection for one of three

  5. Rapid and sensitive immunomagnetic-electrochemiluminescent detection of p53 antibodies in human serum.

    Science.gov (United States)

    Yan, Guihong; Xing, Da; Tan, Shici; Chen, Qun

    2004-05-01

    The mutation of tumor suppressor p53 gene is common in malignant tumor. p53 antibodies are products of immunoresponse against abnormal p53 protein. It has been found that p53 antibodies are of importance in tumor's diagnosis, prognosis and relapse monitoring. However, current method for detecting p53 antibodies, i.e. enzyme-linked immunosorbent assay (ELISA), requires a long time with multiple steps, and the assay is only semi-quantitative. In this work, a protocol for quantitative detection of p53 antibodies in human serum using immunomagnetic electrochemiluminescence (IM-ECL) was devoloped. The immunoassay format consisted of a three antibody sandwich in which a biotinylated capture antibody, was banded with the commercial p53 protein. A detector antibody was added to bind the p53 protein at another site. Then, secondary antibody, labeled with ruthenium(II) tris-bipyridal, was added and, when bound to the bead immunocompiex, generated light in the presence of an excess of tripropylamine. The light was detected and measured by the analyzer made by us. Our experimental results indicate that the sensitivity of this assay was 10 pg of p53 antibodies per ml of reference serum (normal human serum). A stable calibration curve with a wide dynamic range was established. The calibration curve was linear from 0.01 to 1000 ng/ml, thus, making quantitation possible. An immunologic prozone effect was observed above 1000 ng p53 antibodies per milliliter of serum. Serum samples from lung and nasopharyngeal carcinoma patients were tested using the IM-ECL assay. The positive rate of p53 antibodies were 28.6% in lung carcinoma and 8.33% in nasopharyngeal carcinoma, respectively. p53 antibody concentration in the carcerous human sera were quantified from the calibration curve. In the case of lung carcinoma, a trend was found that a higher p53 antibody concentration in the serum was likely linked to a higher stage of the cancer. This trend was not found in nasopharyngeal carcinoma

  6. Construction of Rabbit Immune Antibody Libraries.

    Science.gov (United States)

    Nguyen, Thi Thu Ha; Lee, Jong Seo; Shim, Hyunbo

    2018-01-01

    Rabbits have distinct advantages over mice as a source of target-specific antibodies. They produce higher affinity antibodies than mice, and may elicit strong immune response against antigens or epitopes that are poorly immunogenic or tolerated in mice. However, a great majority of currently available monoclonal antibodies are of murine origin because of the wider availability of murine fusion partner cell lines and well-established tools and protocols for fusion and cloning of mouse hybridoma. Phage-display selection of antibody libraries is an alternative method to hybridoma technology for the generation of target-specific monoclonal antibodies. High-affinity monoclonal antibodies from nonmurine species can readily be obtained by constructing immune antibody libraries from B cells of the immunized animal and screening the library by phage display. In this article, we describe the construction of a rabbit immune Fab library for the facile isolation of rabbit monoclonal antibodies. After immunization, B-cell cDNA is obtained from the spleen of the animal, from which antibody variable domain repertoires are amplified and assembled into a Fab repertoire by PCR. The Fab genes are then cloned into a phagemid vector and transformed to E. coli, from which a phage-displayed immune Fab library is rescued. Such a library can be biopanned against the immunization antigen for rapid identification of high-affinity, target-specific rabbit monoclonal antibodies.

  7. Gravitational-wave astronomy: delivering on the promises.

    Science.gov (United States)

    Schutz, B F

    2018-05-28

    Now that LIGO and Virgo have begun to detect gravitational-wave events with regularity, the field of gravitational-wave astronomy is beginning to realize its promise. Binary black holes and, very recently, binary neutron stars have been observed, and we are already learning much from them. The future, with improved sensitivity, more detectors and detectors like LISA in different frequency bands, has even more promise to open a completely hidden side of the Universe to our exploration.This article is part of a discussion meeting issue 'The promises of gravitational-wave astronomy'. © 2018 The Author(s).

  8. Initiating a watch list for Ebola virus antibody escape mutations

    Directory of Open Access Journals (Sweden)

    Craig R. Miller

    2016-02-01

    Full Text Available The 2014 Ebola virus (EBOV outbreak in West Africa is the largest in recorded history and resulted in over 11,000 deaths. It is essential that strategies for treatment and containment be developed to avoid future epidemics of this magnitude. With the development of vaccines and antibody-based therapies using the envelope glycoprotein (GP of the 1976 Mayinga strain, one important strategy is to anticipate how the evolution of EBOV might compromise these efforts. In this study we have initiated a watch list of potential antibody escape mutations of EBOV by modeling interactions between GP and the antibody KZ52. The watch list was generated using molecular modeling to estimate stability changes due to mutation. Every possible mutation of GP was considered and the list was generated from those that are predicted to disrupt GP-KZ52 binding but not to disrupt the ability of GP to fold and to form trimers. The resulting watch list contains 34 mutations (one of which has already been seen in humans at six sites in the GP2 subunit. Should mutations from the watch list appear and spread during an epidemic, it warrants attention as these mutations may reflect an evolutionary response from the virus that could reduce the effectiveness of interventions such as vaccination. However, this watch list is incomplete and emphasizes the need for more experimental structures of EBOV interacting with antibodies in order to expand the watch list to other epitopes. We hope that this work provokes experimental research on evolutionary escape in both Ebola and other viral pathogens.

  9. Human anti-mouse antibody response induced by anti-CD4 monoclonal antibody therapy in patients with rheumatoid arthritis.

    Science.gov (United States)

    Horneff, G; Winkler, T; Kalden, J R; Emmrich, F; Burmester, G R

    1991-04-01

    The development of human anti-mouse monoclonal antibodies (HAMAs) was investigated in 10 patients with rheumatoid arthritis (RA) who had undergone an experimental therapeutic trial with an anti-CD4 monoclonal antibody. In this patient group, the antibody 16H5 of the IgG1 isotype had been administered in a median total dosage of 140 mg per treatment cycle. Four patients took part in a second treatment regimen 6-8 weeks later. After the first treatment cycle, detectable HAMAs developed in 5 out of 10 patients. In 4 individuals undergoing a second course of therapy, increases of HAMAs were evident only in the 3 patients with previous HAMA responses. HAMAs were primarily of the IgG isotype, while the presence of rheumatoid factors usually interfered with the detectability of IgM HAMAs. However, using isolated F(ab)2 fragments of the monoclonal reagent used for therapy, HAMAs of the IgM isotype were also detectable. HAMAs of the IgG isotype did not exceed levels of 2.0 mg/liter after a single treatment cycle and 2.2 mg/liter after a repeated cycle. No IgE responses were detectable. Absorption experiments indicated that approximately 25% of the HAMA activity was directed against specific determinants of the 16H5 monoclonal antibody, presumably including anti-idiotypic reactivities. These data demonstrate that HAMAs developed only in a proportion of RA patients treated with the anti-CD4 monoclonal antibody 16H5. However, the amounts were rather low compared to other monoclonal reagents used in cancer patients and were therefore allowed for repeated applications without an apparent loss of efficacy.

  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. Promising Practices and Programs: Current Efforts and Future Directions

    Science.gov (United States)

    Crisp, Gloria

    2016-01-01

    The final chapter of the issue provides a synthesis of the first eight chapters, offers conclusions and recommendations, and considers future directions regarding practices and programs with promise for high impact at community colleges around the country.

  12. Promise Zone Round 2 Applicant Geography and Goal Data

    Data.gov (United States)

    Department of Housing and Urban Development — This dataset includes Promise Zone initiative round II applicant project data from 111 urban, rural, and tribal communities who consented to share their application...

  13. Phase Separation in Solutions of Monoclonal Antibodies

    Science.gov (United States)

    Benedek, George; Wang, Ying; Lomakin, Aleksey; Latypov, Ramil

    2012-02-01

    We report the observation of liquid-liquid phase separation (LLPS) in a solution of humanized monoclonal antibodies, IgG2, and the effects of human serum albumin, a major blood protein, on this phase separation. We find a significant reduction of phase separation temperature in the presence of albumin, and a preferential partitioning of the albumin into the antibody-rich phase. We provide a general thermodynamic analysis of the antibody-albumin mixture phase diagram and relate its features to the magnitude of the effective inter-protein interactions. Our analysis suggests that additives (HSA in this report), which have moderate attraction with antibody molecules, may be used to forestall undesirable protein condensation in antibody solutions. Our findings are relevant to understanding the stability of pharmaceutical solutions of antibodies and the mechanisms of cryoglobulinemia.

  14. The future of antibodies as cancer drugs.

    Science.gov (United States)

    Reichert, Janice M; Dhimolea, Eugen

    2012-09-01

    Targeted therapeutics such as monoclonal antibodies (mAbs) have proven successful as cancer drugs. To profile products that could be marketed in the future, we examined the current commercial clinical pipeline of mAb candidates for cancer. Our analysis revealed trends toward development of a variety of noncanonical mAbs, including antibody-drug conjugates (ADCs), bispecific antibodies, engineered antibodies and antibody fragments and/or domains. We found substantial diversity in the antibody sequence source, isotype, carbohydrate residues, targets and mechanisms of action (MOA). Although well-validated targets, such as epidermal growth factor receptor (EGFR) and CD20, continue to provide opportunities for companies, we found notable trends toward targeting less-well-validated antigens and exploration of innovative MOA such as the generation of anticancer immune responses or recruitment of cytotoxic T cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Effect of anti-CD 20 antibody rituximab in patients with post-transplant lymphoproliferative disorder (PTLD)

    NARCIS (Netherlands)

    Oertel, SHK; Verschuuren, E; Reinke, P; Zeidler, K; Papp-Vary, M; Babel, N; Trappe, RU; Jonas, S; Hummel, M; Anagnostopoulos, [No Value; Dorken, B; Riess, HB

    2005-01-01

    Post-transplant lymphoproliferative disorders (PTLD) are a life-threatening complication following solid organ transplantation. Treatment with rituximab, a humanized anti-CD20 monoclonal antibody, has proved to be a promising approach and shown a low toxicity profile. Between February 1999 and April

  16. Anti-S100A4 antibody suppresses metastasis formation by blocking stroma cell invasion

    DEFF Research Database (Denmark)

    Klingelhöfer, Jörg; Grum-Schwensen, Birgitte; Beck, Mette K

    2012-01-01

    microenvironment, making it an attractive target for anti-cancer therapy. In this study, we produced a function-blocking anti-S100A4 monoclonal antibody with metastasis-suppressing activity. Antibody treatment significantly reduced metastatic burden in the lungs of experimental animals by blocking the recruitment......The small Ca-binding protein, S100A4, has a well-established metastasis-promoting activity. Moreover, its expression is tightly correlated with poor prognosis in patients with numerous types of cancer. Mechanistically, the extracellular S100A4 drives metastasis by affecting the tumor...... of T cells to the site of the primary tumor. In vitro studies demonstrated that this antibody efficiently reduced the invasion of T cells in a fibroblast monolayer. Moreover, it was capable of suppressing the invasive growth of human and mouse fibroblasts. We presume therefore that the antibody exerts...

  17. Complement inhibition enables tumor delivery of LCMV glycoprotein pseudotyped viruses in the presence of antiviral antibodies

    Directory of Open Access Journals (Sweden)

    Laura Evgin

    2016-01-01

    Full Text Available The systemic delivery of therapeutic viruses, such as oncolytic viruses or vaccines, is limited by the generation of neutralizing antibodies. While pseudotyping of rhabdoviruses with the lymphocytic choriomeningitis virus glycoprotein has previously allowed for multiple rounds of delivery in mice, this strategy has not translated to other animal models. For the first time, we provide experimental evidence that antibodies generated against the lymphocytic choriomeningitis virus glycoprotein mediate robust complement-dependent viral neutralization via activation of the classical pathway. We show that this phenotype can be capitalized upon to deliver maraba virus pseudotyped with the lymphocytic choriomeningitis virus glycoprotein in a Fischer rat model in the face of neutralizing antibody through the use of complement modulators. This finding changes the understanding of the humoral immune response to arenaviruses, and also describes methodology to deliver viral vectors to their therapeutic sites of action without the interference of neutralizing antibody.

  18. Warm antibody autoimmune hemolytic anemia.

    Science.gov (United States)

    Kalfa, Theodosia A

    2016-12-02

    Autoimmune hemolytic anemia (AIHA) is a rare and heterogeneous disease that affects 1 to 3/100 000 patients per year. AIHA caused by warm autoantibodies (w-AIHA), ie, antibodies that react with their antigens on the red blood cell optimally at 37°C, is the most common type, comprising ∼70% to 80% of all adult cases and ∼50% of pediatric cases. About half of the w-AIHA cases are called primary because no specific etiology can be found, whereas the rest are secondary to other recognizable underlying disorders. This review will focus on the postulated immunopathogenetic mechanisms in idiopathic and secondary w-AIHA and report on the rare cases of direct antiglobulin test-negative AIHA, which are even more likely to be fatal because of inherent characteristics of the causative antibodies, as well as because of delays in diagnosis and initiation of appropriate treatment. Then, the characteristics of w-AIHA associated with genetically defined immune dysregulation disorders and special considerations on its management will be discussed. Finally, the standard treatment options and newer therapeutic approaches for this chronic autoimmune blood disorder will be reviewed. © 2016 by The American Society of Hematology. All rights reserved.

  19. 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...

  20. 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.

  1. 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.

  2. High throughput discovery of influenza virus neutralizing antibodies from phage-displayed synthetic antibody libraries.

    Science.gov (United States)

    Chen, Ing-Chien; Chiu, Yi-Kai; Yu, Chung-Ming; Lee, Cheng-Chung; Tung, Chao-Ping; Tsou, Yueh-Liang; Huang, Yi-Jen; Lin, Chia-Lung; Chen, Hong-Sen; Wang, Andrew H-J; Yang, An-Suei

    2017-10-31

    Pandemic and epidemic outbreaks of influenza A virus (IAV) infection pose severe challenges to human society. Passive immunotherapy with recombinant neutralizing antibodies can potentially mitigate the threats of IAV infection. With a high throughput neutralizing antibody discovery platform, we produced artificial anti-hemagglutinin (HA) IAV-neutralizing IgGs from phage-displayed synthetic scFv libraries without necessitating prior memory of antibody-antigen interactions or relying on affinity maturation essential for in vivo immune systems to generate highly specific neutralizing antibodies. At least two thirds of the epitope groups of the artificial anti-HA antibodies resemble those of natural protective anti-HA antibodies, providing alternatives to neutralizing antibodies from natural antibody repertoires. With continuing advancement in designing and constructing synthetic scFv libraries, this technological platform is useful in mitigating not only the threats of IAV pandemics but also those from other newly emerging viral infections.

  3. Not All Antibodies Are Created Equal: Factors That Influence Antibody Mediated Rejection

    Directory of Open Access Journals (Sweden)

    Carrie L. Butler

    2017-01-01

    Full Text Available Consistent with Dr. Paul Terasaki’s “humoral theory of rejection” numerous studies have shown that HLA antibodies can cause acute and chronic antibody mediated rejection (AMR and decreased graft survival. New evidence also supports a role for antibodies to non-HLA antigens in AMR and allograft injury. Despite the remarkable efforts by leaders in the field who pioneered single antigen bead technology for detection of donor specific antibodies, a considerable amount of work is still needed to better define the antibody attributes that are associated with AMR pathology. This review highlights what is currently known about the clinical context of pre and posttransplant antibodies, antibody characteristics that influence AMR, and the paths after donor specific antibody production (no rejection, subclinical rejection, and clinical dysfunction with AMR.

  4. Assessing the Promise of a Supplemental Reading Intervention for At-Risk First Grade Students in a Public School Setting

    Science.gov (United States)

    Mokhtari, Kouider; Neel, Joanna L.; Kaiser, Forrest; Le, Hong-Hai

    2015-01-01

    In this exploratory quasi-experimental case study, we assessed the promise of a yearlong supplemental reading intervention with a small pilot group of at-risk first grade readers in an elementary school setting. Using standardized measures of reading proficiency, we found that after 47 hours of one-on-one tutoring instruction, students read…

  5. Ultrasensitive detection of clenbuterol by a covalent imprinted polymer as a biomimetic antibody.

    Science.gov (United States)

    Tang, Yiwei; Gao, Jingwen; Liu, Xiuying; Gao, Xue; Ma, Tao; Lu, Xiaonan; Li, Jianrong

    2017-08-01

    As an ideal biomimetic antibody, molecularly imprinted polymer (MIP) has shown great promise in immunoassays. Here, we developed a covalent imprinting method to prepare MIP artificial antibody towards clenbuterol on the well surface of a microtiter plate. Template molecule (clenbuterol) was splited by hydrolysis with functional monomer and removed by methanol/acetic acid solution, and then three-dimensional cavities were fabricated in the MIP, which can rebind template molecule via hydrogen bond interaction. Using this artificial antibody, we developed a novel biomimetic enzyme-linked immunosorbent assay (ELISA) with excellent sensitivity and specificity. The linear range for clenbuterol was 10 -5 to 1000μgL -1 , with a detection limit of 10 -7 μgL -1 . Cross reactivity of this MIP artificial antibody to other four structural analogs was less than 0.93%. This method was applied to determine clenbuterol in real samples with satisfactory result, suggesting a promising application of the biomimetic ELISA in food and environmental analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Human anti-Dectin-1 antibody, hybridoma producing said antibody and applications thereof

    OpenAIRE

    Kremer, Leonor; Llorente Gómez, María de las Mercedes; Casasnovas, José María; Fernández Ruíz, Elena; Galán Díez, Marta

    2008-01-01

    [EN] The invention relates to hybridoma MGD3 and the monoclonal antibody produced thereby (also called MGD3), which specifically recognises the human Dectin-1 membrane receptor. Antibody MGD3 is capable of inhibiting the binding of Dectin-1 to the natural ligand thereof, the ss-glucans that are components of the fungal wall. In addition, the aforementioned antibody specifically blocks binding to Candida albicans and the secretion of cytokines induced thereby. The MGD3 antibody obtained enable...

  7. 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....

  8. Using the natural evolution of a rotavirus-specific human monoclonal antibody to predict the complex topography of a viral antigenic site

    Science.gov (United States)

    McKinney, Brett A; Kallewaard, Nicole L; Crowe, James E; Meiler, Jens

    2007-01-01

    Background Understanding the interaction between viral proteins and neutralizing antibodies at atomic resolution is hindered by a lack of experimentally solved complexes. Progress in computational docking has led to the prediction of increasingly high-quality model antibody-antigen complexes. The accuracy of atomic-level docking predictions is improved when integrated with experimental information and expert knowledge. Methods Binding affinity data associated with somatic mutations of a rotavirus-specific human adult antibody (RV6-26) are used to filter potential docking orientations of an antibody homology model with respect to the rotavirus VP6 crystal structure. The antibody structure is used to probe the VP6 trimer for candidate interface residues. Results Three conformational epitopes are proposed. These epitopes are candidate antigenic regions for site-directed mutagenesis of VP6, which will help further elucidate antigenic function. A pseudo-atomic resolution RV6-26 antibody-VP6 complex is proposed consistent with current experimental information. Conclusion The use of mutagenesis constraints in docking calculations allows for the identification of a small number of alternative arrangements of the antigen-antibody interface. The mutagenesis information from the natural evolution of a neutralizing antibody can be used to discriminate between residue-scale models and create distance constraints for atomic-resolution docking. The integration of binding affinity data or other information with computation may be an advantageous approach to assist peptide engineering or therapeutic antibody design. PMID:17877819

  9. Smoking and periodontal disease: discrimination of antibody responses to pathogenic and commensal oral bacteria.

    Science.gov (United States)

    Hayman, L; Steffen, M J; Stevens, J; Badger, E; Tempro, P; Fuller, B; McGuire, A; Al-Sabbagh, Mohanad; Thomas, M V; Ebersole, J L

    2011-04-01

    Smoking is an independent risk factor for the initiation, extent and severity of periodontal disease. This study examined the ability of the host immune system to discriminate commensal oral bacteria from pathogens at mucosal surfaces, i.e. oral cavity. Serum immunoglobulin (Ig)G antibody reactive with three pathogenic and five commensal oral bacteria in 301 current smokers (age range 21-66 years) were examined by enzyme-linked immunosorbent assay. Clinical features of periodontal health were used as measures of periodontitis. Antibody to the pathogens and salivary cotinine levels were related positively to disease severity; however, the antibody levels were best described by the clinical disease unrelated to the amount of smoking. The data showed a greater immune response to pathogens than commensals that was related specifically to disease extent, and most noted in black males. Significant correlations in individual patient responses to the pathogens and commensals were lost with an increasing extent of periodontitis and serum antibody to the pathogens. Antibody to Porphyromonas gingivalis was particularly distinct with respect to the discriminatory nature of the immune responses in recognizing the pathogens. Antibody responses to selected pathogenic and commensal oral microorganisms differed among racial groups and genders. The antibody response to the pathogens was related to disease severity. The level of antibody to the pathogens, and in particular P. gingivalis, was correlated with disease severity in black and male subsets of patients. The amount of smoking did not appear to impact directly serum antibody levels to these oral bacteria. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

  10. 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

  11. Experimental philosophy.

    Science.gov (United States)

    Knobe, Joshua; Buckwalter, Wesley; Nichols, Shaun; Robbins, Philip; Sarkissian, Hagop; Sommers, Tamler

    2012-01-01

    Experimental philosophy is a new interdisciplinary field that uses methods normally associated with psychology to investigate questions normally associated with philosophy. The present review focuses on research in experimental philosophy on four central questions. First, why is it that people's moral judgments appear to influence their intuitions about seemingly nonmoral questions? Second, do people think that moral questions have objective answers, or do they see morality as fundamentally relative? Third, do people believe in free will, and do they see free will as compatible with determinism? Fourth, how do people determine whether an entity is conscious?

  12. [The development of biochip to detect anti-cholera antibodies in human blood serum].

    Science.gov (United States)

    Utkin, D V; Osina, N A; Spitsin, A N; Kireev, M N; Gromova, O V; Zakharova, T L; Naidenova, E V; Kuklev, V E

    2015-02-01

    The full-scaled agglutinating immunoassay is commonly applied to detect content of antibodies to cholera agent Vibrio cholerae human in blood serum under application of serological diagnostic. The time of analysis implementation amounts to 18 hours. To shorten time of detection of antibodies a biological microchip (biochip) was developed. The biochip represents an activated slide with immobilized corpuscle and soluble antigen cholera agent (O-antigens, cholera toxin). The experimental work resulted in development of scheme of biochip and selection of optimal conditions of sorption and implementation of immunologic analysis using biochip. The application of biochip facilitated to detect specific antibodies to antigens of cholera agent in commercial experimental animal serums and blood serums of ill patients. The time of analysis implementation amounted to 2-3 hours. The results are substantiated by bacteriological and serological methods.

  13. PROMISE AND PLAUSIBILITY: HEALTH TECHNOLOGY ADOPTION DECISIONS WITH LIMITED EVIDENCE.

    Science.gov (United States)

    Campbell, Bruce; Knox, Paul

    2016-01-01

    The adoption of new medical devices and diagnostics is often hampered by lack of published evidence which makes conventional health technology assessment (HTA) difficult. We now have 5 years' experience of the Medical Technologies Advisory Committee of the National Institute for Health and Care Excellence (NICE) in the United Kingdom, addressing this problem. This committee assesses devices and diagnostics against claims of advantage, to produce guidance on adoption for the health service. We have reflected on the practical, technical, and intellectual processes we have used in developing guidance for the health service. When scientific and clinical evidence is sparse, promise and plausibility play an increased part in decision-making. Drivers of promise include a clear design and mechanism of action, the possibility of radical improvement in care and/or resource use, and improving health outcomes for large numbers of patients. Plausibility relates to judgements about the whether the promise is likely to be delivered in a "real world" setting. Promise and plausibility need to be balanced against the amount of evidence available. We examine the influence they may have on decision-making compared with other factors such as risk and cost. Decisions about adoption of new devices and diagnostics with little evidence are influenced by judgements of their promise and the plausibility of claims that they will provide benefits in a real-world setting. This kind of decision making needs to be transparent and this article explains how these influences can be balanced against the use of more familiar criteria.

  14. TSOL18 Vaccine Antigen of Taenia solium: Development of Monoclonal Antibodies and Field Testing of the Vaccine in Cameroon

    Directory of Open Access Journals (Sweden)

    Assana, E.

    2010-01-01

    Full Text Available Chapter 1 reviews the literature about the immunological aspects of taeniid cestode infections and the existing vaccines against Taenia solium cysticercosis in pigs. One of the most promising vaccines is TSOL18, a protein that has been identified in the oncosphere of Taenia solium and expressed as a recombinant molecule in E. coli. Repeated experimental trials have shown that this vaccine is able to protect up to 100% of the immunised pigs against a challenge infection with T. solium. Antibodies raised by the vaccine are capable of killing the parasite in in vitro cultures and it is believed that antibody and complement mediated killing of invading parasites is the major protective immune mechanism induced by vaccination with TSOL18. The identification of the villages with a high risk of T. solium infection, which could subsequently be used in the vaccine trial, is reported in chapter 2. A survey was conducted in 150 households owning 1756 pigs in the rural areas of Mayo-Danay division in the far north region of Cameroon. A questionnaire survey was carried out to collect information on the pig farming system and to identify potential risk factors for T. solium cysticercosis infection in pigs. Blood samples were collected from 398 pigs with the aim of estimating the sero-prevalence of Taenia solium cysticercosis. The results showed that 90.7% of the pigs were free roaming during the dry season and that 42.7% of households keeping pigs in the rural areas had no latrine facility. Seventy six percent of the interviewed pig owners affirmed that the members of the household used open field defecation. ELISA for antigen and antibody detection showed an apparent prevalence of porcine cysticercosis of 24.6% and 32.2%, respectively. A Bayesian approach using the conditional dependence between the two diagnostic tests indicated that the true sero-prevalence of cysticercosis in Mayo-Danay was 26.6%. Binary logistic regression analysis indicated that the

  15. E.coli and investigation of antibody titer in rats

    Directory of Open Access Journals (Sweden)

    masoud abdollahi

    2017-03-01

    Full Text Available Introduction: Plant ribosome inactivating proteins act as N-glycosidase enzyme and produce by several family of Caryophyllaceae such as Saponaria Officinalis. Different Isoforms of RIPs expressed by Saponaria Officinalis. SO6 isoform depurinate Adenine 4324 in the conserved GAGA loop of 28SrRNA and disrupts protein synthesis. The aim of this study was expression of SO6 isoform in E.coli and investigation of antibody titer in rats. Methods: In this experimental study, SO6 synthetic gene was excised from recombinant pUC57- SO6 plasmid with BamHI and SalI restriction enzymes and subcloned into pET28a (+ expression vector. The expression of recombinant protein was induced by IPTG. Recombinant SO6 was purified by nickel affinity chromatography. Western blotting was performed to confirm the recombinant protein. Rats were immunized intraperitoneal with purified protein and IgG serum titer was assayed by ELISA. Results: PCR reaction and enzyme digestion confirmed subcloning of SO6 gene into pET28a (+ expression vector. A 29.5kDa protein band on SDS-PAGE showed a high level of recombinant protein expression. Polyclonal antibodies recognized SO6. ELISA confirmed significant antibody titer after injection of protein in test group compared with the control group. Conclusion: The recombinant purified SO6 antigen can be used for anti-cancer and vaccine candidate research.

  16. Relevant shaking stress conditions for antibody preformulation development.

    Science.gov (United States)

    Eppler, Annette; Weigandt, Markus; Hanefeld, Andrea; Bunjes, Heike

    2010-02-01

    In protein formulation development, shaking stress is often employed to assess the physical stability of antibody formulations against aggregation. Since there are currently no guidelines describing suitable test conditions, very different shaking stress designs are used. These different designs may influence the resulting stability data. The aim of this study was to establish a shaking stress design within the protein range of 2-5mg/ml which can rapidly distinguish between antibody formulations of poor stability and those with potential for further development. Small scale shaking stress experiments were performed with different monoclonal IgG antibodies (as buffered solutions or marketed formulations). Variables were the filling degree of the sample containers, the container type and size and the shaking intensity. The stability of the samples was assessed by visual inspection, UV-VIS spectrophotometric turbidity measurements and size exclusion chromatography. All tested parameters had a strong influence on the stability results. The most discriminating conditions were obtained when shaking of the formulations was performed at 200rpm in a 2ml injection vial filled with 1ml protein solution. This experimental setup led to clearly different stability results for buffered solutions and marketed products. Moreover, this setup required only relatively small amounts of protein solution which is advantageous in prefomulation studies. Copyright (c) 2009 Elsevier B.V. All rights reserved.

  17. Beneficial impact of CCL2 and CCL12 neutralization on experimental malignant pleural effusion.

    Directory of Open Access Journals (Sweden)

    Antonia Marazioti

    Full Text Available Using genetic interventions, we previously determined that C-C motif chemokine ligand 2 (CCL2 promotes malignant pleural effusion (MPE formation in mice. Here we conducted preclinical studies aimed at assessing the specific therapeutic potential of antibody-mediated CCL2 blockade against MPE. For this, murine MPEs or skin tumors were generated in C57BL/6 mice by intrapleural or subcutaneous delivery of lung (LLC or colon (MC38 adenocarcinoma cells. Human lung adenocarcinoma cells (A549 were used to induce MPEs in severe combined immunodeficient mice. Intraperitoneal antibodies neutralizing mouse CCL2 and/or CCL12, a murine CCL2 ortholog, were administered at 10 or 50 mg/kg every three days. We found that high doses of CCL2/12 neutralizing antibody treatment (50 mg/kg were required to limit MPE formation by LLC cells. CCL2 and CCL12 blockade were equally potent inhibitors of MPE development by LLC cells. Combined CCL2 and CCL12 neutralization was also effective against MC38-induced MPE and prolonged the survival of mice in both syngeneic models. Mouse-specific CCL2-blockade limited A549-caused xenogeneic MPE, indicating that host-derived CCL2 also contributes to MPE precipitation in mice. The impact of CCL2/12 antagonism was associated with inhibition of immune and vascular MPE-related phenomena, such as inflammation, new blood vessel assembly and plasma extravasation into the pleural space. We conclude that CCL2 and CCL12 blockade are effective against experimental MPE induced by murine and human adenocarcinoma in mice. These results suggest that CCL2-targeted therapies may hold promise for future use against human MPE.

  18. 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

  19. Update on antiphospholipid antibody syndrome

    Directory of Open Access Journals (Sweden)

    Michelle Remião Ugolini Lopes

    Full Text Available Summary 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.

  20. [Equilibrium and kinetic parameters of the interaction of strophanthin K and its peroxidase conjugates with soluble and immobilized specific antibodies].

    Science.gov (United States)

    Tarun, E I; Savenkova, M I; Metelitsa, D I

    1995-07-01

    Using solid phase enzyme-linked immunoassay (ELISA), rate constants for the formation and dissociation as well as equilibrium dissociation constants for strophanthin complexes interaction with specific antibodies (both soluble and immobilized on activated polystyrene beads and polyamide membranes) have been determined. A satisfactory correlation was found between dissociation constants for immune complexes determined by ELISA (both soluble and immobilized ones) and associations constants for these complexes determined by the Scatchard method. The experimental values of kinetic and equilibrium constants for strophanthin K and its peroxidase complexes interaction reflect the difference in the nature of interacting particles and their environment. Strophanthin complexes with antibodies appeared to be more stable when formed on adsorbents (in comparison with those formed in solution). Strophanthin interaction with immobilized antibodies occurred at a slower rate than that with soluble antibodies. Strophanthin reacts with antibodies more readily than its complexes both in solution and on solid matrices of various polymeric nature.

  1. Non-Culture Diagnostics for Invasive Candidiasis: Promise and Unintended Consequences

    Science.gov (United States)

    Clancy, Cornelius J.; Nguyen, M. Hong

    2018-01-01

    Blood cultures are positive for Candida species in candidiasis, respectively. Non-culture tests such as mannan, anti-mannan antibody, Candida albicans germ tube antibody (CAGTA), 1,3-β-d-glucan (BDG), the T2Candida nanodiagnostic panel, and polymerase chain reaction (PCR) are available for clinical use, but their roles in patient care are uncertain. Sensitivity/specificity of combined mannan/anti-mannan, BDG, T2Candida and PCR for candidemia are ~80%/80%, ~80%/80%, ~90%/98%, and ~90%/90%, respectively. Limited data for intra-abdominal candidiasis suggest CAGTA, BDG sensitivity/specificity of ~65%/75% and PCR sensitivity of ~85–90%. PCR specificity has varied widely for intra-abdominal candidiasis (33–97%), and T2Candida data are lacking. Tests will be useful if restricted to cases in which positive and negative predictive values (PPVs, NPVs) differ in a clinically meaningful way from the pre-test likelihood of invasive candidiasis. In some patients, PPVs are sufficient to justify antifungal treatment, even if blood cultures are negative. In most patients, NPVs of each test are excellent, which may support decisions to withhold antifungal therapy. If test results are not interpreted judiciously, non-culture diagnostics may have unintended consequences for stewardship and infection prevention programs. In particular, discrepant non-culture test-positive/culture-negative results may promote inappropriate antifungal treatment of patients who are unlikely to have candidiasis, and lead to spurious reporting of hospital-acquired infections. In conclusion, non-culture Candida diagnostics have potential to advance patient care, but this promise will be realized only if users understand tests’ strengths and limitations, and plan proactively for how best to employ them at their hospitals. PMID:29463043

  2. Experimental studies

    International Nuclear Information System (INIS)

    Cowser, K.E.; Stansbury, P.S.; Poston, J.W.; Deus, S.F.; Chen, W.L.; Roswell, R.L.; Goans, R.E.; Cantrell, J.H. Jr.

    1978-01-01

    Spectral fluence measurements in an adult phantom are reported. A NaI(Tl) probe was used in various locations within the phantom and pulse-height spectra were obtained for seven beam configurations and three generating potentials. Some typical spectra results are presented. A comparison of calculated dose to experimental measurements is presented

  3. Experimental guidelines

    International Nuclear Information System (INIS)

    1997-01-01

    The paper proposes a model experimental design to study the effects of pesticides on particular ecosystem. It takes maize as a model crop and an alternative crop while studying the adverse effects on untargeted arthropods, residues in the soil and other plants. 5 refs, 7 figs

  4. Transcutaneous Immunization with a Band-Aid Prevents Experimental Otitis Media in a Polymicrobial Model.

    Science.gov (United States)

    Novotny, Laura A; Clements, John D; Goodman, Steven D; Bakaletz, Lauren O

    2017-06-01

    Otitis media (OM) is a common pediatric disease, and nontypeable Haemophilus influenzae (NTHI) is the predominant pathogen in chronic OM, recurrent OM, and OM associated with treatment failure. OM is also a polymicrobial disease, wherein an upper respiratory tract viral infection predisposes to ascension of NTHI from the nasopharynx, the site of colonization, to the normally sterile middle ear, resulting in disease. Using a clinically relevant viral-bacterial coinfection model of NTHI-induced OM, we performed transcutaneous immunization (TCI) via a band-aid delivery system to administer each of three promising NTHI vaccine candidates derived from bacterial adhesive proteins and biofilm mediators: recombinant soluble PilA (rsPilA), chimV4, and integration host factor. Each immunogen was admixed with the adjuvant LT(R192G/L211A), a double mutant of Escherichia coli heat-labile enterotoxin, and assessed for relative ability to prevent the onset of experimental OM. For each cohort, the presence of circulating immunogen-specific antibody-secreting cells and serum antibody was confirmed prior to intranasal NTHI challenge. After bacterial challenge, blinded video otoscopy and tympanometry revealed a significant reduction in the proportion of animals with signs of OM compared to levels in animals receiving adjuvant only, with an overall vaccine efficacy of 64 to 77%. These data are the first to demonstrate the efficacy afforded by TCI with a band-aid vaccine delivery system in a clinically relevant polymicrobial model of OM. The simplicity of TCI with a band-aid and the significant efficacy observed here hold great promise for reducing the global burden of OM in the pediatric population. Copyright © 2017 American Society for Microbiology.

  5. 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)

  6. [Radiolabeled antibodies for cancer treatment].

    Science.gov (United States)

    Barbet, Jacques; Chatal, Jean-François; Kraeber-Bodéré, Françoise

    2009-12-01

    The first treatment ever by radio-immunotherapy (RIT) was performed by William H. Beierwaltes in 1951 and was a success. Fifty years later, the main question is to find ways of extending the success of radiolabelled anti-CD20 antibodies in indolent non-Hodgkin's lymphoma to other forms of cancer. Solid tumours are much more radioresistant than lymphomas, but they respond to RIT if the lesions are small. Clinical situations of residual or minimal disease are thus the most likely to benefit from RIT in the adjuvant or consolidation settings. For disseminated disease, like leukemias or myelomas, the problem is different: beta- particles emitted by the radioactive atoms classically used for cancer treatment (iodine-131 or yttrium-90) disperse their energy in large volumes (ranges 1 mm to 1 cm) and are not very effective against isolated cells. Advances in RIT progress in two directions. One is the development of pretargeting strategies in which the antibody is not labelled but used to provide binding sites to small molecular weight radioactivity vectors (biotin, haptens). These techniques have been shown to increase tumour to non-target uptake ratios and anti-tumour efficacy has been demonstrated in the clinic. The other approach is the use of radionuclides adapted to the various clinical situations. Lutetium-177 or copper-67, because of the lower energy of their emission, their relatively long half-life and good gamma emission, may significantly improve RIT efficacy and acceptability. Beyond that, radionuclides emitting particles such as alpha particles or Auger electrons, much more efficient to kill isolated tumour cells, are being tested for RIT in the clinic. Finally, RIT should be integrated with other cancer treatment approaches in multimodality protocols. Thus RIT, now a mature technology, should enter a phase of well designed and focused clinical developments that may be expected to afford significant therapeutic advances.

  7. Congestion Service Facilities Location Problem with Promise of Response Time

    Directory of Open Access Journals (Sweden)

    Dandan Hu

    2013-01-01

    Full Text Available In many services, promise of specific response time is advertised as a commitment by the service providers for the customer satisfaction. Congestion on service facilities could delay the delivery of the services and hurts the overall satisfaction. In this paper, congestion service facilities location problem with promise of response time is studied, and a mixed integer nonlinear programming model is presented with budget constrained. The facilities are modeled as M/M/c queues. The decision variables of the model are the locations of the service facilities and the number of servers at each facility. The objective function is to maximize the demands served within specific response time promised by the service provider. To solve this problem, we propose an algorithm that combines greedy and genetic algorithms. In order to verify the proposed algorithm, a lot of computational experiments are tested. And the results demonstrate that response time has a significant impact on location decision.

  8. Copenhagen's climate finance promise: six key questions

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, J. Timmons [Brown University (United States); Stadelmann, Martin [University of Zurich (Switzerland); Huq, Saleemul

    2010-02-15

    One clear promise emerged from the confusion of the 2009 climate talks in Copenhagen. This was to provide short- and long-term 'climate finance' to help developing countries – especially the most vulnerable – adapt to climate impacts. The promise seemed simple enough: wealthier nations would pledge US$10 billion a year from 2010-2012, ramping up to US$100 billion a year starting in 2020. This was also touted as a way to help developing countries avoid high-carbon pathways of development by adopting lower-emitting power sources such as solar or natural gas. But a closer look at the Copenhagen promise unearths at least six big questions – any one of which could seriously challenge the trust these funds were designed to build.

  9. 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.

  10. Monoclonal antibodies against rat leukocyte surface antigens

    NARCIS (Netherlands)

    van den Berg, T. K.; Puklavec, M. J.; Barclay, A. N.; Dijkstra, C. D.

    2001-01-01

    Monoclonal antibodies have proven to be powerful tools for studying the properties of leukocyte surface antigens and the cells that express them. In the past decades many monoclonal antibodies (mAb) for identifying the different rat leukocyte surface antigens have been described. A list of mAb is

  11. Quantitative Changes In Antibodies Against Onchocercal Native ...

    African Journals Online (AJOL)

    Quantitative Changes In Antibodies Against Onchocercal Native Antigens Two Months Postivermectin Treatment Of Onchocerciasis Patients. ... Those without onchocercal skin disease, OSD (n=18) had a significant increase of 20.5±29.6%, with pre- and posttreatment values of 0.59±0.15 versus 0.68±0.13 for IgG antibody ...

  12. Anti-influenza M2e antibody

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew M.

    2013-04-16

    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.

  13. Anti-influenza M2e antibody

    Energy Technology Data Exchange (ETDEWEB)

    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.

  14. 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.

  15. Serum Antiphospholipid Antibodies Among Healthy Adults In ...

    African Journals Online (AJOL)

    Background: Antiphospholipid antibodies have been associated with variety of conditions. There is no standard health associated reference values required for the interpretation of antiphospholipid antibodies result available among adults in North- eastern Nigeria and Nigeria in general. The aim of this study is to determine ...

  16. Determination of antiphospholipid antibodies and Thrombophilia in ...

    African Journals Online (AJOL)

    Background: Recurrent miscarriage is a critical problem in which many factors play a crucial role such as antiphospholipid antibodies (APA) and anticardiolipin antibodies (ACA). Recent studies pointed to a potential role of thrombophilias as a possible cause of recurrent miscarriage (RM). Objectives: This study was ...

  17. 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.

  18. 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.

  19. [Monoclonal antibodies for the treatment of multiple sclerosis].

    Science.gov (United States)

    Sánchez-Seco, Victoria Galán; Casanova Peño, Ignacio; Arroyo González, Rafael

    2014-12-01

    Until the mid 1990s, with the appearance of interferon beta and glatiramer acetate, there was no treatment for multiple sclerosis (MS). However, due to their moderate therapeutic potential in some patients, a broad search was continued to find new and more effective treatment strategies, largely concentrated on monoclonal antibodies (MOAB). Natalizumab, the first MOAB for the treatment of MS, was approved at the end of 2004, representing a major advance in the field of neuroimmunology. Today, there is broad experience with natalizumab and other MOAB (alemtuzumab, daclizumab, rituximab, ocrelizumab, ofatumumab and anti-lingo-1) that are pending commercialization or are under phase II or III of development with promising results. The present review analyzes the efficacy and safety results of all these drugs. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  20. CD47 limits antibody dependent phagocytosis against non-malignant B cells.

    Science.gov (United States)

    Gallagher, Sandra; Turman, Sean; Lekstrom, Kristen; Wilson, Susan; Herbst, Ronald; Wang, Yue

    2017-05-01

    Recent studies have demonstrated the importance of CD47 in protecting malignant B cells from antibody dependent cellular phagocytosis (ADCP). Combined treatment of anti-CD47 and -CD20 antibodies synergistically augment elimination of tumor B cells in xenograft mouse models. This has led to the development of novel reagents that can potentially enhance killing of malignant B cells in patients. B cell depleting therapy is also a promising treatment for autoimmune patients. In the current study, we aimed to investigate whether or not CD47 protects non-malignant B cells from ADCP. We show that CD47 is expressed on all B cells in mice, with the highest level on plasma cells in bone marrow and spleen. Although its expression is dispensable for B cell development in mice, CD47 on B cells limits antibody mediated phagocytosis. B cell depletion following in vivo anti-CD19 treatment is more efficient in CD47-/- mice than in wild type mice. In vitro, both naïve and activated B cells from CD47-/- mice are more sensitive to ADCP than wild type B cells. Lastly, we show in an ADCP assay that blocking CD47 can enhance anti-CD19 antibody mediated phagocytosis of wild type B cells. These results suggest that in addition to its already demonstrated benefit in cancer, targeting CD47 may be used as an adjunct in combination with B cell depletion antibodies for treatment of autoimmune diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Big data analytics in healthcare: promise and potential.

    Science.gov (United States)

    Raghupathi, Wullianallur; Raghupathi, Viju

    2014-01-01

    To describe the promise and potential of big data analytics in healthcare. The paper describes the nascent field of big data analytics in healthcare, discusses the benefits, outlines an architectural framework and methodology, describes examples reported in the literature, briefly discusses the challenges, and offers conclusions. The paper provides a broad overview of big data analytics for healthcare researchers and practitioners. Big data analytics in healthcare is evolving into a promising field for providing insight from very large data sets and improving outcomes while reducing costs. Its potential is great; however there remain challenges to overcome.

  2. Promising design options for the encapsulated nuclear heat source reactor

    Energy Technology Data Exchange (ETDEWEB)

    Conway, L.; Carelli, M.D.; Dzodzo, M. [Westinghouse Science and Technology, Pittsburgh, PA (United States); Hossain, Q.; Brown, N.W. [Lawrence Livermore National Lab., CA (United States); Wade, D.C.; Sienick, J.J. [Argonne National Lab., IL (United States); Greenspan, E.; Kastenberg, W.E.; Saphier, D. [University of California Dept of Nuclear Engineering, Berkeley, CA (United States)

    2001-07-01

    Promising design options for the Encapsulated Nuclear Heat Source (ENHS) liquid-metal cooled fast reactor were identified during the first year of the DOE NERI program sponsored feasibility study. Many opportunities for incorporation of innovations in design and fabrication were identified. Three of the innovations are hereby described: a novel IHX (intermediate heat exchanger) made of a relatively small number of rectangular channels, an ENHS module design featuring 100% natural circulation, and a novel conceptual design of core support and fuelling. As a result of the first year study the ENHS concept appears more practical and more promising than perceived at the outset of this study. (authors)

  3. Promising design options for the encapsulated nuclear heat source reactor

    International Nuclear Information System (INIS)

    Conway, L.; Carelli, M.D.; Dzodzo, M.; Hossain, Q.; Brown, N.W.; Wade, D.C.; Sienick, J.J.; Greenspan, E.; Kastenberg, W.E.; Saphier, D.

    2001-01-01

    Promising design options for the Encapsulated Nuclear Heat Source (ENHS) liquid-metal cooled fast reactor were identified during the first year of the DOE NERI program sponsored feasibility study. Many opportunities for incorporation of innovations in design and fabrication were identified. Three of the innovations are hereby described: a novel IHX (intermediate heat exchanger) made of a relatively small number of rectangular channels, an ENHS module design featuring 100% natural circulation, and a novel conceptual design of core support and fuelling. As a result of the first year study the ENHS concept appears more practical and more promising than perceived at the outset of this study. (authors)

  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. 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...... response was studied with serum samples collected in 1992 from 56 CF patients in a cross-sectional study and with serum samples from 18 CF patients in a longitudinal study. Anti-beta-lactamase immunoglobulin G antibodies were present in all of the serum samples from the patients with chronic...... bronchopulmonary P. aeruginosa infection (CF + P) but in none of the CF patients with no or intermittent P. aeruginosa infection. Anti-beta-lactamase antibodies were present in serum from CF + P patients after six antipseudomonal courses (median) and correlated with infection with a beta-lactam-resistant strain...

  6. Onconeural antibodies: improved detection and clinical correlations.

    Science.gov (United States)

    Storstein, Anette; Monstad, Sissel Evy; Haugen, Mette; Mazengia, Kibret; Veltman, Dana; Lohndal, Emilia; Aarseth, Jan; Vedeler, Christian

    2011-03-01

    Onconeural antibodies are found in many patients with paraneoplastic neurological syndromes (PNS) and define the disease as paraneoplastic. The study describes the presence of onconeural antibodies and PNS in 555 patients with neurological symptoms and confirmed cancer within five years, and compares the diagnostic accuracy of different antibody assays (immunoprecipitation, immunofluorescence and immunoblot). Onconeural antibodies were found in 11.9% of the patients by immunoprecipitation, in 7.0% by immunofluorescence and in 6.3% by immunoblot. PNS were present in 81.8% of the cancer patients that were seropositive by immunoprecipitation. Immunofluorescence and immunoblot failed to detect onconeural antibodies in almost one third of the PNS cases. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Variance decomposition of protein profiles from antibody arrays using a longitudinal twin model

    Directory of Open Access Journals (Sweden)

    Kato Bernet S

    2011-11-01

    Full Text Available Abstract Background The advent of affinity-based proteomics technologies for global protein profiling provides the prospect of finding new molecular biomarkers for common, multifactorial disorders. The molecular phenotypes obtained from studies on such platforms are driven by multiple sources, including genetic, environmental, and experimental components. In characterizing the contribution of different sources of variation to the measured phenotypes, the aim is to facilitate the design and interpretation of future biomedical studies employing exploratory and multiplexed technologies. Thus, biometrical genetic modelling of twin or other family data can be used to decompose the variation underlying a phenotype into biological and experimental components. Results Using antibody suspension bead arrays and antibodies from the Human Protein Atlas, we study unfractionated serum from a longitudinal study on 154 twins. In this study, we provide a detailed description of how the variation in a molecular phenotype in terms of protein profile can be decomposed into familial i.e. genetic and common environmental; individual environmental, short-term biological and experimental components. The results show that across 69 antibodies analyzed in the study, the median proportion of the total variation explained by familial sources is 12% (IQR 1-22%, and the median proportion of the total variation attributable to experimental sources is 63% (IQR 53-72%. Conclusion The variability analysis of antibody arrays highlights the importance to consider variability components and their relative contributions when designing and evaluating studies for biomarker discoveries with exploratory, high-throughput and multiplexed methods.

  8. Tumor infarction in mice by antibody-directed targeting of tissue factor to tumor vasculature

    NARCIS (Netherlands)

    Huang, XM; Molema, G; King, S; Watkins, L; Edgington, TS; Thorpe, PE

    1997-01-01

    Selective occlusion of tumor vasculature was tested as a therapy for solid tumors in a mouse model. The formation of blood clots (thrombosis) within the tumor Vessels was initiated by targeting the cell surface domain of human tissue factor, by means of a bispecific antibody, to an experimentally

  9. Serum anti-BPAG1 auto-antibody is a novel marker for human melanoma.

    Directory of Open Access Journals (Sweden)

    Takashi Shimbo

    2010-05-01

    Full Text Available Malignant melanoma is one of the most aggressive types of tumor. Because malignant melanoma is difficult to treat once it has metastasized, early detection and treatment are essential. The search for reliable biomarkers of early-stage melanoma, therefore, has received much attention. By using a novel method of screening tumor antigens and their auto-antibodies, we identified bullous pemphigoid antigen 1 (BPAG1 as a melanoma antigen recognized by its auto-antibody. BPAG1 is an auto-antigen in the skin disease bullous pemphigoid (BP and anti-BPAG1 auto-antibodies are detectable in sera from BP patients and are used for BP diagnosis. However, BPAG1 has been viewed as predominantly a keratinocyte-associated protein and a relationship between BPAG1 expression and melanoma has not been previously reported. In the present study, we show that bpag1 is expressed in the mouse F10 melanoma cell line in vitro and F10 melanoma tumors in vivo and that BPAG1 is expressed in human melanoma cell lines (A375 and G361 and normal human melanocytes. Moreover, the levels of anti-BPAG1 auto-antibodies in the sera of melanoma patients were significantly higher than in the sera of healthy volunteers (p<0.01. Furthermore, anti-BPAG1 auto-antibodies were detected in melanoma patients at both early and advanced stages of disease. Here, we report anti-BPAG1 auto-antibodies as a promising marker for the diagnosis of melanoma, and we discuss the significance of the detection of such auto-antibodies in cancer biology and patients.

  10. Anti-tau antibody administration increases plasma tau in transgenic mice and patients with tauopathy.

    Science.gov (United States)

    Yanamandra, Kiran; Patel, Tirth K; Jiang, Hong; Schindler, Suzanne; Ulrich, Jason D; Boxer, Adam L; Miller, Bruce L; Kerwin, Diana R; Gallardo, Gilbert; Stewart, Floy; Finn, Mary Beth; Cairns, Nigel J; Verghese, Philip B; Fogelman, Ilana; West, Tim; Braunstein, Joel; Robinson, Grace; Keyser, Jennifer; Roh, Joseph; Knapik, Stephanie S; Hu, Yan; Holtzman, David M

    2017-04-19

    Tauopathies are a group of disorders in which the cytosolic protein tau aggregates and accumulates in cells within the brain, resulting in neurodegeneration. A promising treatment being explored for tauopathies is passive immunization with anti-tau antibodies. We previously found that administration of an anti-tau antibody to human tau transgenic mice increased the concentration of plasma tau. We further explored the effects of administering an anti-tau antibody on plasma tau. After peripheral administration of an anti-tau antibody to human patients with tauopathy and to mice expressing human tau in the central nervous system, there was a dose-dependent increase in plasma tau. In mouse plasma, we found that tau had a short half-life of 8 min that increased to more than 3 hours after administration of anti-tau antibody. As tau transgenic mice accumulated insoluble tau in the brain, brain soluble and interstitial fluid tau decreased. Administration of anti-tau antibody to tau transgenic mice that had decreased brain soluble tau and interstitial fluid tau resulted in an increase in plasma tau, but this increase was less than that observed in tau transgenic mice without these brain changes. Tau transgenic mice subjected to acute neuronal injury using 3-nitropropionic acid showed increased interstitial fluid tau and plasma tau. These data suggest that peripheral administration of an anti-tau antibody results in increased plasma tau, which correlates with the concentration of extracellular and soluble tau in the brain. Copyright © 2017, American Association for the Advancement of Science.

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

    Energy Technology Data Exchange (ETDEWEB)

    Surinder Batra, Ph D

    2006-02-27

    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

  12. 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

  13. The development of an Enzyme Linked Immunosorbent Assay for detecting Injectious laryngotrachitis viral antibodies in chicken serum

    Directory of Open Access Journals (Sweden)

    Risa Indriani

    2002-06-01

    Full Text Available The aim of this study was to develop an Enzyme-linked immunosorbent assay (ELISA for detection of antibody against gallid herpes virus, the causal agent of infectious laryngotracheitis (ILT in chicken. Its application in experimental chicken under laboratory condition was also evaluated. Results showed that ELISA for ILT was developed successfully with sensitivity and specificity was 98% and 97,14% respectively. The ELISA was able to determine the dynamic of antibodies respond in experimental chickens following vaccination and artificial infection with ILT virus. It was concluded that this ELISA offers a simple, sensitive and specific antibody assay for detection of antibodies against ILT virus in chickens arising from vaccination or infection.

  14. Designing novel nano-immunoassays: antibody orientation versus sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Puertas, S; Moros, M; Fernandez-Pacheco, R; Ibarra, M R; Grazu, V; De la Fuente, J M, E-mail: vgrazu@unizar.e, E-mail: jmfuente@unizar.e [Instituto de Nanociencia de Aragon (INA), Universidad de Zaragoza, Campus RIo Ebro, EdifIcio I-D, Mariano Esquillor, s/n, 50018 Zaragoza (Spain)

    2010-12-01

    There is a growing interest in the use of magnetic nanoparticles (MNPs) for their application in quantitative and highly sensitive biosensors. Their use as labels of biological recognition events and their detection by means of some magnetic method constitute a very promising strategy for quantitative high-sensitive lateral-flow assays. In this paper, we report the importance of nanoparticle functionalization for the improvement of sensitivity for a lateral-flow immunoassay. More precisely, we have found that immobilization of IgG anti-hCG through its polysaccharide moieties on MNPs allows more successful recognition of the hCG hormone. Although we have used the detection of hCG as a model in this work, the strategy of binding antibodies to MNPs through its sugar chains reported here is applicable to other antibodies. It has huge potential as it will be very useful for the development of quantitative and high-sensitive lateral-flow assays for its use on human and veterinary, medicine, food and beverage manufacturing, pharmaceutical, medical biologics and personal care product production, environmental remediation, etc.

  15. Promising applications of graphene and graphene-based nanostructures

    Science.gov (United States)

    Nguyen, Bich Ha; Hieu Nguyen, Van

    2016-06-01

    The present article is a review of research works on promising applications of graphene and graphene-based nanostructures. It contains five main scientific subjects. The first one is the research on graphene-based transparent and flexible conductive films for displays and electrodes: efficient method ensuring uniform and controllable deposition of reduced graphene oxide thin films over large areas, large-scale pattern growth of graphene films for stretchble transparent electrodes, utilization of graphene-based transparent conducting films and graphene oxide-based ones in many photonic and optoelectronic devices and equipments such as the window electrodes of inorganic, organic and dye-sensitized solar cells, organic light-emitting diodes, light-emitting electrochemical cells, touch screens, flexible smart windows, graphene-based saturated absorbers in laser cavities for ultrafast generations, graphene-based flexible, transparent heaters in automobile defogging/deicing systems, heatable smart windows, graphene electrodes for high-performance organic field-effect transistors, flexible and transparent acoustic actuators and nanogenerators etc. The second scientific subject is the research on conductive inks for printed electronics to revolutionize the electronic industry by producing cost-effective electronic circuits and sensors in very large quantities: preparing high mobility printable semiconductors, low sintering temperature conducting inks, graphene-based ink by liquid phase exfoliation of graphite in organic solutions, and developing inkjet printing technique for mass production of high-quality graphene patterns with high resolution and for fabricating a variety of good-performance electronic devices, including transparent conductors, embedded resistors, thin-film transistors and micro supercapacitors. The third scientific subject is the research on graphene-based separation membranes: molecular dynamics simulation study on the mechanisms of the transport of

  16. Radiohalogenated half-antibodies and maleimide intermediate therefor

    Science.gov (United States)

    Kassis, Amin I.; Khawli, Leslie A.

    1991-01-01

    N-(m-radiohalophenyl) maleimide can be conjugated with a reduced antibody having a mercapto group to provide a radiolabelled half-antibody having immunological specific binding characteristics of whole antibody.

  17. 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...

  18. Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection.

    Directory of Open Access Journals (Sweden)

    Kshitij Wagh

    2016-03-01

    Full Text Available The identification of a new generation of potent broadly neutralizing HIV-1 antibodies (bnAbs has generated substantial interest in their potential use for the prevention and/or treatment of HIV-1 infection. While combinations of bnAbs targeting distinct epitopes on the viral envelope (Env will likely be required to overcome the extraordinary diversity of HIV-1, a key outstanding question is which bnAbs, and how many, will be needed to achieve optimal clinical benefit. We assessed the neutralizing activity of 15 bnAbs targeting four distinct epitopes of Env, including the CD4-binding site (CD4bs, the V1/V2-glycan region, the V3-glycan region, and the gp41 membrane proximal external region (MPER, against a panel of 200 acute/early clade C HIV-1 Env pseudoviruses. A mathematical model was developed that predicted neutralization by a subset of experimentally evaluated bnAb combinations with high accuracy. Using this model, we performed a comprehensive and systematic comparison of the predicted neutralizing activity of over 1,600 possible double, triple, and quadruple bnAb combinations. The most promising bnAb combinations were identified based not only on breadth and potency of neutralization, but also other relevant measures, such as the extent of complete neutralization and instantaneous inhibitory potential (IIP. By this set of criteria, triple and quadruple combinations of bnAbs were identified that were significantly more effective than the best double combinations, and further improved the probability of having multiple bnAbs simultaneously active against a given virus, a requirement that may be critical for countering escape in vivo. These results provide a rationale for advancing bnAb combinations with the best in vitro predictors of success into clinical trials for both the prevention and treatment of HIV-1 infection.

  19. Experimental insertions

    International Nuclear Information System (INIS)

    Sandweiss, J.; Kycia, T.F.

    1975-01-01

    A discussion is given of the eight identical experimental insertions for the planned ISABELLE storage rings. Four sets of quadrupole doublets are used to match the β functions in the insertions to the values in the cells, and the total free space available at the crossing point is 40 meters. An asymmetric beam energy operation is planned, which will be useful in a number of experiments

  20. Animal experimentation

    OpenAIRE

    Laz, Alak; Cholakova, Tanya Stefanova; Vrablova, Sofia; Arshad, Naverawaheed

    2016-01-01

    Animal experimentation is a crucial part of medical science. One of the ways to define it is any scientific experiment conducted for research purposes that cause any kind of pain or suffering to animals. Over the years, the new discovered drugs or treatments are first applied on animals to test their positive outcomes to be later used by humans. There is a debate about violating ethical considerations by exploiting animals for human benefits. However, different ethical theories have been made...

  1. Animal experimentation.

    Science.gov (United States)

    Kolar, Roman

    2006-01-01

    Millions of animals are used every year in often times extremely painful and distressing scientific procedures. Legislation of animal experimentation in modern societies is based on the supposition that this is ethically acceptable when certain more or less defined formal (e.g. logistical, technical) demands and ethical principles are met. The main parameters in this context correspond to the "3Rs" concept as defined by Russel and Burch in 1959, i.e. that all efforts to replace, reduce and refine experiments must be undertaken. The licensing of animal experiments normally requires an ethical evaluation process, often times undertaken by ethics committees. The serious problems in putting this idea into practice include inter alia unclear conditions and standards for ethical decisions, insufficient management of experiments undertaken for specific (e.g. regulatory) purposes, and conflicts of interest of ethics committees' members. There is an ongoing societal debate about ethical issues of animal use in science. Existing EU legislation on animal experimentation for cosmetics testing is an example of both the public will for setting clear limits to animal experiments and the need to further critically examine other fields and aspects of animal experimentation.

  2. Promising Practices in Drug Treatment: Findings from Southeast Asia

    Science.gov (United States)

    Libretto, Salvatore; Nemes, Susanna; Namur, Jenny; Garrett, Gerald; Hess, Lauren; Kaplan, Linda

    2005-01-01

    In a study to evaluate the drug treatment and aftercare efforts sponsored by the State Department's International Narcotics and Law Enforcement Affairs Bureau, residential Therapeutic Community (TC) treatment programs in three countries in Southeast Asia--Malaysia, Singapore, and Thailand--were examined to identify promising practices and to…

  3. Promising Practices in Drug Treatment: An Overview of Methodology

    Science.gov (United States)

    Garrett, Gerald; Nemes, Susanna; Hoffman, Jeffrey; Libretto, Salvatore; Skinstadt, Anne Helene; Hess, Lauren

    2005-01-01

    This paper describes a research project sponsored and funded by the State Department's Bureau of International Narcotics and Affairs (INL) on substance abuse and treatment in ten countries. The purpose of the study was to identify promising practices in drug treatment in Europe, Latin America, and Southeast Asia. The steps taken to complete this…

  4. Pomological and phenological characteristics of promising rose hip ...

    African Journals Online (AJOL)

    This study was carried out to determine pomological and phenological characteristics of eleven promising rose hip (Rosa) genotypes chosen from wild populations in Tokat region of northern Anatolia, Turkey. Plants were propagated by cuttings and planted in 2000 at the research station of the Horticultural Department of ...

  5. Augmented Reality Based Doppler Lidar Data Visualization: Promises and Challenges

    Directory of Open Access Journals (Sweden)

    Cherukuru N. W.

    2016-01-01

    As a proof of concept, we used the lidar data from a recent field campaign and developed a smartphone application to view the lidar scan in augmented reality. In this paper, we give a brief methodology of this feasibility study, present the challenges and promises of using AR technology in conjunction with Doppler wind lidars.

  6. Understanding the promises and premises of online health platforms

    NARCIS (Netherlands)

    van Dijck, J.; Poell, T.

    2016-01-01

    This article investigates the claims and complexities involved in the platform-based economics of health and fitness apps. We examine a double-edged logic inscribed in these platforms, promising to offer personal solutions to medical problems while also contributing to the public good. On the one

  7. 78 FR 63913 - Proposed Priority-Promise Zones

    Science.gov (United States)

    2013-10-25

    ... neighborhood a child grows up in affects his or her odds of graduating from high school, health outcomes, and... to ensure that hard-working Americans make it to the middle class. Promise Zones will align the work... are creating jobs, increasing economic activity, improving educational opportunities, reducing violent...

  8. Promises of Money Meant to Heighten Student Motivation

    Science.gov (United States)

    Ash, Katie

    2008-01-01

    Does motivating students to study harder with the promise of cash sound like innovation--or bribery? That's a question educators and researchers have been debating, amid concerns that money-for-achievement programs actually decrease students' intrinsic motivation to learn and send mixed messages about studying. But the idea is catching on, with…

  9. History in the Junior College Classroom: Problems and Promise.

    Science.gov (United States)

    Hurst, James W.

    This paper assesses the problems faced in teaching history in the junior college classroom and the promise of and possibilities for new departures in the instructor's role. The problems are seen as: 1) the question of emphasis within the junior college curriculum; 2) the widespread vocational-technical orientation of students and administrators;…

  10. Vachellia karroo leaf meal: a promising non-conventional feed ...

    African Journals Online (AJOL)

    Vachellia karroo leaf meal: a promising non-conventional feed resource for improving goat production in low-input farming systems of Southern Africa. ... Vachellia karroo possesses desirable fatty acid profiles, and high protein and mineral contents that can improve animal performance. Presently, the use of V. karroo for ...

  11. Postmodernism and the need for story and promise: How Robert ...

    African Journals Online (AJOL)

    Modernity's belief that we live in a narratable world (a world with a story) and its confidence in progress (a world with a promise), are terminated by postmodernism's insights. This is how the American Lutheran theologian Robert Jenson understands the impact of postmodernism. If this is true, it poses great challenges for the ...

  12. Promise and Progress of Millihertz Gravitational-Wave Astronomy

    Science.gov (United States)

    Baker, John G.

    2017-01-01

    Extending the new field of gravitational wave (GW) astronomy into the millihertz band with a space-based GW observatory is a high-priority objective of international astronomy community. This paper summarizes the astrophysical promise and the technological groundwork for such an observatory, concretely focusing on the prospects for the proposed Laser Interferometer Space Antenna (LISA) mission concept.

  13. Rulers against Writers, Writers against Rulers: The Failed Promise of ...

    African Journals Online (AJOL)

    Various literary critics have dwelt on the nature, tenets and trends of commitment in Nigeria literature. However, there is paucity of scholarly studies on the representations of the failed promise to the public sphere in postcolonial Nigerian fiction. This paper, therefore, examines the strategies and technicalities of representing ...

  14. Dendritic cell vaccines in melanoma: from promise to proof?

    NARCIS (Netherlands)

    Lesterhuis, W. J.; Aarntzen, E. H. J. G.; de Vries, I. J. M.; Schuurhuis, D. H.; Figdor, C. G.; Adema, G. J.; Punt, C. J. A.

    2008-01-01

    Dendritic cells (DC) are the directors of the immune system, capable of inducing tumour antigen-specific T- and B-cell responses. As such, they are currently applied in clinical studies in cancer patients. Early small clinical trials showed promising results, with frequent induction of anti-cancer

  15. Reducing Aggressive Male Behavior in Elementary School: Promising Practices

    Science.gov (United States)

    Holmes, Barbara; Gibson, Jamel; Morrison-Danner, Dietrich

    2014-01-01

    Student aggression and violent behavior, especially among males, is pervasive and problematic in the classroom. When incorporated in the lesson design, promising practices (music, movement, and visual stimulation) are evidence-based strategies that may reduce male aggression in the classroom.

  16. Promising Teacher Practices: Students' Views about Their Science Learning

    Science.gov (United States)

    Moeed, Azra; Easterbrook, Matthew

    2016-01-01

    Internationally, conceptual and procedural understanding, understanding the Nature of Science, and scientific literacy are considered worthy goals of school science education in modern times. The empirical study presented here reports on promising teacher practices that in the students' views afford learning opportunities and support their science…

  17. The Pittsburgh Promise: A Community's Commitment to Its Young People

    Science.gov (United States)

    Ghubril, Saleem

    2013-01-01

    The nonprofit community-based organization Pittsburgh Promise aims to help revitalize Pittsburgh and its public school system by offering college scholarships to any Pittsburgh Public School graduate who meets the academic requirements. Executive director Saleem Ghubril spoke with "Voices in Urban Education" guest editor Jacob Mishook…

  18. Immobilization of microbial cells: A promising tool for treatment of ...

    African Journals Online (AJOL)

    Suzana

    2013-07-10

    Jul 10, 2013 ... Review. Immobilization of microbial cells: A promising tool for treatment of toxic pollutants in industrial ... immobilized microorganisms could be cost effective since they can be used several times without ..... controlling the cell immobilization on the support (Hsu et al., 2004, Górecka and Jastrzębska, 2011).

  19. Infliximab (Revellex(R)): a promise fulfilled?: medicine in practice ...

    African Journals Online (AJOL)

    Infliximab (Revellex(R)): a promise fulfilled?: medicine in practice. JP Wright. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners ...

  20. Prion Protein-Specific Antibodies-Development, Modes of Action and Therapeutics Application

    Directory of Open Access Journals (Sweden)

    Tihana Lenac Rovis

    2014-10-01

    Full Text Available Prion diseases or Transmissible Spongiform Encephalopathies (TSEs are lethal neurodegenerative disorders involving the misfolding of the host encoded cellular prion protein, PrPC. This physiological form of the protein is expressed throughout the body, and it reaches the highest levels in the central nervous system where the pathology occurs. The conversion into the pathogenic isoform denoted as prion or PrPSc is the key event in prion disorders. Prominent candidates for the treatment of prion diseases are antibodies and their derivatives. Anti-PrPC antibodies are able to clear PrPSc from cell culture of infected cells. Furthermore, application of anti-PrPC antibodies suppresses prion replication in experimental animal models. Major drawbacks of immunotherapy are immune tolerance, the risks of neurotoxic side effects, limited ability of compounds to cross the blood-brain barrier and their unfavorable pharmacokinetic. The focus of this review is to recapitulate the current understanding of the molecular mechanisms for antibody mediated anti-prion activity. Although relevant for designing immunotherapeutic tools, the characterization of key antibody parameters shaping the molecular mechanism of the PrPC to PrPSc conversion remains elusive. Moreover, this review illustrates the various attempts towards the development of anti-PrP antibody compounds and discusses therapeutic candidates that modulate PrP expression.

  1. Natural and cross-inducible anti-SIV antibodies in Mauritian cynomolgus macaques.

    Directory of Open Access Journals (Sweden)

    Hongzhao Li

    Full Text Available Cynomolgus macaques are an increasingly important nonhuman primate model for HIV vaccine research. SIV-free animals without pre-existing anti-SIV immune responses are generally needed to evaluate the effect of vaccine-induced immune responses against the vaccine epitopes. Here, in order to select such animals for vaccine studies, we screened 108 naïve female Mauritian cynomolgus macaques for natural (baseline antibodies to SIV antigens using a Bio-Plex multiplex system. The antigens included twelve 20mer peptides overlapping the twelve SIV protease cleavage sites (-10/+10, respectively (PCS peptides, and three non-PCS Gag or Env peptides. Natural antibodies to SIV antigens were detected in subsets of monkeys. The antibody reactivity to SIV was further confirmed by Western blot using purified recombinant SIV Gag and Env proteins. As expected, the immunization of monkeys with PCS antigens elicited anti-PCS antibodies. However, unexpectedly, antibodies to non-PCS peptides were also induced, as shown by both Bio-Plex and Western blot analyses, while the non-PCS peptides do not share sequence homology with PCS peptides. The presence of natural and vaccine cross-inducible SIV antibodies in Mauritian cynomolgus macaques should be considered in animal selection, experimental design and result interpretation, for their best use in HIV vaccine research.

  2. Radioimmunoassay of IgM and IgG antitetanus toxoid antibody

    International Nuclear Information System (INIS)

    Repetti, C.F.; Gill, T.J. III

    1980-01-01

    A radioimmunoassay was developed to quantitate antitetanus toxoid antibody in whole plasma which can detect 0.75 ng IgG antibody (0.75 μg/ml plasma) and 1.60 ng IgM antibody (0.40 μg/ml plasma). The IgG antibody was measured by direct binding to a tetanus toxoid-Sepharose immunoadsorbent. The IgM antibody was measured by inhibition of binding by soluble tetanus toxoid because of the relatively high and erratic non-specific reaction between IgM and the immunoadsorbent. The immunoglobulin standards were [ 131 I]IgG or [ 131 I]IgM coupled to Sepharose, respectively, and the amount of antibody activity in the 125 I-labeled antiglobulin reagents could be calculated from the amount bound to the immunoadsorbent and the specific activity of the appropriate immunoglobulin standard. The assay is sensitive, reproducible and suitable for use with large numbers of samples: it should find wide applicability in both clinical and experimental settings. (Auth.)

  3. Antibody response to Mycoplasma hyopneumoniae infection in vaccinated pigs with or without maternal antibodies induced by sow vaccination.

    Science.gov (United States)

    Martelli, P; Terreni, M; Guazzetti, S; Cavirani, S

    2006-06-01

    Vaccination with bacterins is an important tool for the control of Mycoplasma hyopneumoniae infection of pigs. Because such vaccination often involves piglets that have suckled M. hyopneumoniae antibody-positive dams it is important to understand the effect of pre-existing (passively acquired) antibody on vaccine-induced immunity. To investigate this issue experimentally, 20 sows that were seronegative for M. hyopneumoniae were selected from a M. hyopneumoniae-infected herd and then randomly allocated to one of four treatment groups (five sows/group): Group A, vaccinated sows/vaccinated piglets; Group B, vaccinated sows/non-vaccinated piglets; Group C, non-vaccinated sows/vaccinated piglets; Group D, non-vaccinated sows/non-vaccinated piglets. Sows (Groups A and B) were vaccinated 14 days before farrowing and seroconverted within the next 14 days. Conversely, none of the non-vaccinated sows was seropositive at farrowing. Piglets (Groups A and C) were vaccinated when they were 7 days of age. Regardless of treatments none of the piglets had any evidence of an active immune response until many of those of Groups A and C and a few of those of Groups B and D seroconverted after it had been shown that at least some pigs of all groups had been naturally infected with a field strain of M. hyopneumoniae. This pattern of immune responsiveness (i.e. the collective results of Groups A, B, C and D) suggested that vaccination of pigs had primed their immune system for subsequent exposure to M. hyopneumoniae, and that passively acquired antibody had little or no effect on either a vaccine-induced priming or a subsequent anamnestic response. According to the statistical analysis sow serological status did not interfere with the antibody response in early vaccinated piglets. In conclusion, the results pointed out that early vaccination of piglets may assist M. hyopneumoniae control independently from the serological status of sows.

  4. Augmentation of antibody-dependent cellular cytotoxicity with defucosylated monoclonal antibodies in patients with GI-tract cancer.

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    Nakajima, Takahiro; Okayama, Hirokazu; Ashizawa, Mai; Noda, Masaru; Aoto, Keita; Saito, Motonobu; Monma, Tomoyuki; Ohki, Shinji; Shibata, Masahiko; Takenoshita, Seiichi; Kono, Koji

    2018-02-01

    Enhancement of antibody-dependent cellular cytotoxicity (ADCC) with some modalities may be a promising approach to enhance the efficacy of therapeutic monoclonal antibodies (mAbs). It has previously been demonstrated that the removal of fucose from antibody oligosaccharides (defucosylation) leads to augmentation of ADCC activity. To establish clinically relevant evidence of this procedure, the present study evaluated trastuzumab- and cetuximab-mediated ADCC by comparing defucosylated mAbs with conventional mAbs using peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from 20 patients with gastrointestinal tract cancer and 10 healthy volunteers. ADCCs were measured using PBMCs as effector cells and two gastric cancer cell lines as target cells. ADCCs were significantly enhanced with defucosylated mAbs compared with conventional mAbs using PBMC from the healthy donors and patients with cancer. The results confirmed that the cetuximab- and trastuzumab-mediated ADCCs in advanced disease were impaired in comparison to those in early disease or healthy individuals. However, when the defucosylated mAbs were used instead of the conventional mAbs, the ADCC activities in the advanced cases were almost comparable with those in early disease or healthy individuals. Furthermore, the expression of ADCC associated molecules were modified toward immunosuppressive status with a mitogen-activated protein kinase inhibitor in vitro , the conventional cetuximab- and trastuzumab-mediated ADCC was downregulated, and the defucosylated mAbs overcome the downregulation of ADCC. In conclusion, defucosylated therapeutic mAbs may enhance ADCC activities in patients with cancer, which may lead to more effective anti-cancer treatments.

  5. Computational Docking of Antibody-Antigen Complexes, Opportunities and Pitfalls Illustrated by Influenza Hemagglutinin

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    Mattia Pedotti

    2011-01-01

    Full Text Available Antibodies play an increasingly important role in both basic research and the pharmaceutical industry. Since their efficiency depends, in ultimate analysis, on their atomic interactions with an antigen, studying such interactions is important to understand how they function and, in the long run, to design new molecules with desired properties. Computational docking, the process of predicting the conformation of a complex from its separated components, is emerging as a fast and affordable technique for the structural characterization of antibody-antigen complexes. In this manuscript, we first describe the different computational strategies for the modeling of antibodies and docking of their complexes, and then predict the binding of two antibodies to the stalk region of influenza hemagglutinin, an important pharmaceutical target. The purpose is two-fold: on a general note, we want to illustrate the advantages and pitfalls of computational docking with a practical example, using different approaches and comparing the results to known experimental structures. On a more specific note, we want to assess if docking can be successful in characterizing the binding to the same influenza epitope of other antibodies with unknown structure, which has practical relevance for pharmaceutical and biological research. The paper clearly shows that some of the computational docking predictions can be very accurate, but the algorithm often fails to discriminate them from inaccurate solutions. It is of paramount importance, therefore, to use rapidly obtained experimental data to validate the computational results.

  6. Fabrication of calix[4]arene derivative monolayers to control orientation of antibody immobilization.

    Science.gov (United States)

    Chen, Hongxia; Liu, Feng; Qi, Fangjie; Koh, Kwangnak; Wang, Keming

    2014-03-31

    Three calix[4]arene (Cal-4) derivatives which separately contain ethylester (1), carboxylic acid (2), and crownether (3) at the lower rim with a common reactive thiol at the upper rim were synthesized and constructed to self-assembled monolayers (SAMs) on Au films. After spectroscopic characterization of the monolayers, surface coverage and orientation of antibody immobilized on the Cal-4 derivative SAMs were studied by surface plasmon resonance (SPR) technique. Experimental results revealed that the antibody could be immobilized on the Cal-4 derivatives spontaneously. The orientation of absorbed antibody on the Cal-4 derivative SAMs is related to the SAM's dipole moment. The possible orientations of the antibody immobilized on the Cal-4 derivative 1 SAM are lying-on or side-on, while on the Cal-4 derivative 2 and Cal-4 derivative 3 head-on and end-on respectively. These experimental results demonstrate the surface dipole moment of Cal-4 derivative appears to be an important factor to antibody orientation. Cal-4 derivatives are useful in developing site direct protein chips.

  7. Fabrication of Calix[4]arene Derivative Monolayers to Control Orientation of Antibody Immobilization

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    Hongxia Chen

    2014-03-01

    Full Text Available Three calix[4]arene (Cal-4 derivatives which separately contain ethylester (1, carboxylic acid (2, and crownether (3 at the lower rim with a common reactive thiol at the upper rim were synthesized and constructed to self-assembled monolayers (SAMs on Au films. After spectroscopic characterization of the monolayers, surface coverage and orientation of antibody immobilized on the Cal-4 derivative SAMs were studied by surface plasmon resonance (SPR technique. Experimental results revealed that the antibody could be immobilized on the Cal-4 derivatives spontaneously. The orientation of absorbed antibody on the Cal-4 derivative SAMs is related to the SAM’s dipole moment. The possible orientations of the antibody immobilized on the Cal-4 derivative 1 SAM are lying-on or side-on, while on the Cal-4 derivative 2 and Cal-4 derivative 3 head-on and end-on respectively. These experimental results demonstrate the surface dipole moment of Cal-4 derivative appears to be an important factor to antibody orientation. Cal-4 derivatives are useful in developing site direct protein chips.

  8. The Promised Savior in Pre-Islamic Great Religions

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    Mahin Arab

    2014-08-01

    Full Text Available Since the ancient times the belief in the rise of the Reformer has been a fundamental principle. Many of the holy prophets have announced the advent of new prophet. Moreover in the announcements and indications of predecessors there are always allusions to "the Last Promised" and "the Savior of Last Days" under such titles as "Kalki", "Fifth Buddha", "Soshyans", "Messiah", "The Son of Man" and so on and so forth. Of course there are different types of belief in the last reformer in religions. In one place the Savior is merely a social reformer while in another place he is only after the spiritual salvation of people and even sometimes he undertakes both tasks. On the other hand, the Last Promised is once nationalist and once seeks to save the whole world.    This essay seeks to assay the views of pre-Islamic great religions including Zoroastrianism, Judaism, Christianity, Hinduism and Buddhism as to the Promised Savior. This essay is an analytico-descriptive research which has based itself on the first hand works comprising the sacred scriptures of religions and proceeds through the typological analyses of idea of the Promised in religions.    Zoroastrianism: the idea of the Promised has been tied to the notion of Soshyant. Generally speaking, this notion alludes to a group of people who periodically emerge at the end of every millennium of the last three millennia of world's age so as to uproot evil and renew the world, the last one of these reformers is Soshyans. According to the aforementioned typology, Zoroastrian idea of Last Savior is among the Promised who saves the whole world. Moreover Zoroastrian Promised cannot be declared only a social savior as he is not wholly detached from people's spirituality too. From another point of view, Zoroastrian idea of the Promised represents a universal and not nationalist savior who is relatively a human and not divine entity who emerges in the last millennium of world's age.    Judaism: in the

  9. The Promised Savior in Pre-Islamic Great Religions

    Directory of Open Access Journals (Sweden)

    Mahin Arab

    2014-09-01

    Full Text Available Since the ancient times the belief in the rise of the Reformer has been a fundamental principle. Many of the holy prophets have announced the advent of new prophet. Moreover in the announcements and indications of predecessors there are always allusions to "the Last Promised" and "the Savior of Last Days" under such titles as "Kalki", "Fifth Buddha", "Soshyans", "Messiah", "The Son of Man" and so on and so forth. Of course there are different types of belief in the last reformer in religions. In one place the Savior is merely a social reformer while in another place he is only after the spiritual salvation of people and even sometimes he undertakes both tasks. On the other hand, the Last Promised is once nationalist and once seeks to save the whole world.    This essay seeks to assay the views of pre-Islamic great religions including Zoroastrianism, Judaism, Christianity, Hinduism and Buddhism as to the Promised Savior. This essay is an analytico-descriptive research which has based itself on the first hand works comprising the sacred scriptures of religions and proceeds through the typological analyses of idea of the Promised in religions.    Zoroastrianism: the idea of the Promised has been tied to the notion of Soshyant. Generally speaking, this notion alludes to a group of people who periodically emerge at the end of every millennium of the last three millennia of world's age so as to uproot evil and renew the world, the last one of these reformers is Soshyans. According to the aforementioned typology, Zoroastrian idea of Last Savior is among the Promised who saves the whole world. Moreover Zoroastrian Promised cannot be declared only a social savior as he is not wholly detached from people's spirituality too. From another point of view, Zoroastrian idea of the Promised represents a universal and not nationalist savior who is relatively a human and not divine entity who emerges in the last millennium of world's age.    Judaism: in the

  10. Proteomic profiling of antibody-inducing immunogens in tumor tissue identifies PSMA1, LAP3, ANXA3, and maspin as colon cancer markers

    Science.gov (United States)

    Yang, Qian; Roehrl, Michael H.; Wang, Julia Y.

    2018-01-01

    We hypothesized that cancer tissue immunogens – antigens capable of inducing specific antibody production in patients – are promising targets for development of precision diagnostics and humoral immunotherapies. We developed an innovative immuno-proteomic strategy and identified new immunogenic markers of colon cancer. Proteins from cancers and matched normal tissues were separated by 2D gel electrophoresis and blotted with serum antibodies from the same patients. Antibody-reactive proteins were sequenced by mass spectrometry and validated by Western blotting and immunohistochemistry. 170 serum antibody-reactive proteins were identified only in cancerous but not matched normal. Among these, proteasome subunit alpha type 1 (PSA1), leucine aminopeptidase 3 (LAP3), annexin A3 (ANXA3), and maspin (serpin B5) were reproducibly found in tissues from three patients. Differential expression patterns were confirmed in samples from eight patients with various stages of colon adenocarcinoma and liver metastases. These tumor-resident proteins and/or their associated serum antibodies may be promising markers for colon cancer screening and early diagnosis. Furthermore, tumor tissue-specific antibodies could potentially be exploited as immunotherapeutic targets against cancer. More generally, proteomic profiling of antibody-inducing cancer-associated immunogens represents a powerful generic method for uncovering the tumor antigen-ome, i.e., the totality of immunogenic tumor-associated proteins. PMID:29423100

  11. Antiphospholipid Antibodies in Lupus Nephritis.

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    Ioannis Parodis

    Full Text Available Lupus nephritis (LN is a major manifestation of systemic lupus erythematosus (SLE. It remains unclear whether antiphospholipid antibodies (aPL alter the course of LN. We thus investigated the impact of aPL on short-term and long-term renal outcomes in patients with LN. We assessed levels of aPL cross-sectionally in SLE patients diagnosed with (n = 204 or without (n = 294 LN, and prospectively in 64 patients with active biopsy-proven LN (52 proliferative, 12 membranous, before and after induction treatment (short-term outcomes. Long-term renal outcome in the prospective LN cohort was determined by the estimated glomerular filtration rate (eGFR and the Chronic Kidney Disease (CKD stage, after a median follow-up of 11.3 years (range: 3.3-18.8. Cross-sectional analysis revealed no association between LN and IgG/IgM anticardiolipin or anti-β2-glycoprotein I antibodies, or lupus anticoagulant. Both aPL positivity and levels were similar in patients with active LN and non-renal SLE. Following induction treatment for LN, serum IgG/IgM aPL levels decreased in responders (p<0.005 for all, but not in non-responders. Both at active LN and post-treatment, patients with IgG, but not IgM, aPL had higher creatinine levels compared with patients without IgG aPL. Neither aPL positivity nor levels were associated with changes in eGFR from either baseline or post-treatment through long-term follow-up. Moreover, aPL positivity and levels both at baseline and post-treatment were similar in patients with a CKD stage ≥3 versus 1-2 at the last follow-up. In conclusion, neither aPL positivity nor levels were found to be associated with the occurrence of LN in SLE patients. However, IgG aPL positivity in LN patients was associated with a short-term impairment of the renal function while no effect on long-term renal outcome was observed. Furthermore, IgG and IgM aPL levels decreased following induction treatment only in responders, indicating that aPL levels are

  12. Structure Based Antibody-Like Peptidomimetics

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    Mark I. Greene

    2012-02-01

    Full Text Available Biologics such as monoclonal antibodies (mAb and soluble receptors represent new classes of therapeutic agents for treatment of several diseases. High affinity and high specificity biologics can be utilized for variety of clinical purposes. Monoclonal antibodies have been used as diagnostic agents when coupled with radionuclide, immune modulatory agents or in the treatment of cancers. Among other limitations of using large molecules for therapy the actual cost of biologics has become an issue. There is an effort among chemists and biologists to reduce the size of biologics which includes monoclonal antibodies and receptors without a reduction of biological efficacy. Single chain antibody, camel antibodies, Fv fragments are examples of this type of deconstructive process. Small high-affinity peptides have been identified using phage screening. Our laboratory used a structure-based approach to develop small-size peptidomimetics from the three-dimensional structure of proteins with immunoglobulin folds as exemplified by CD4 and antibodies. Peptides derived either from the receptor or their cognate ligand mimics the functions of the parental macromolecule. These constrained peptides not only provide a platform for developing small molecule drugs, but also provide insight into the atomic features of protein-protein interactions. A general overview of the reduction of monoclonal antibodies to small exocyclic peptide and its prospects as a useful diagnostic and as a drug in the treatment of cancer are discussed.

  13. Glycosylation profiles of therapeutic antibody pharmaceuticals.

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    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.

  14. Biodistribution of Yttrium-90-Labeled Anti-CD45 Antibody in a Nonhuman Primate Model

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    Nemecek, Eneida; Hamlin, Donald K.; Fisher, Darrell R.; Krohn, Kenneth A.; Pagel, John M.; Applebaum, F. R.; Press, Oliver W.; Matthews, Dana C.

    2005-01-15

    Radioimmunotherapy may improve the outcome of hematopoietic cell transplantation for hematologic malignancies by delivering targeted radiation to hematopoietic organs while relatively sparing nontarget organs. We evaluated the organ localization of yttrium-90-labeled anti-CD45 (90Y-anti-CD45) antibody in macaques, a model that had previously predicted iodine-131-labeled anti-CD-45 (131I-anti-CD45) antibody biodistribution in humans. Experimental Design: Twelve Macaca nemestrina primates received anti-CD45 antibody labeled with 1 to 2 mCi of 90Y followed by serial blood sampling and marrow and lymph node biopsies, and necropsy. The content of 90Y per gram of tissue was determined by liquid scintillation spectrometry. Time-activity curves were constructed using average isotope concentrations in each tissue at measured time points to yield the fractional residence time and estimate radiation absorbed doses for each organ per unit of administered activity. The biodistribution of 90Y-anti-CD45 antibody was then compared with that previously obtained with 131I-anti-CD45 antibody in macaques. Results: The spleen received 2,120, marrow 1,060, and lymph nodes 315 cGy/mCi of 90Y injected. The liver and lungs were the nontarget organs receiving the highest radiation absorbed doses (440 and 285 cGy/mCi, respectively). Ytrrium-90-labeled anti-CD45 antibody delivered 2.5- and 3.7-fold more radiation to marrow than to liver and lungs, respectively. The ratios previously observed with 131I-antiCD45 antibody were 2.5-and 2.2-fold more radiation to marrow than to liver and lungs, respectively. Conclusions: This study shows that 90Y-anti-CD45 antibody can deliver relatively selective radiation to hematopoietic tissues, with similar ratios of radiation delivered to target versus nontarget organs, as compared with the 131I immunoconjugate in the same animal model.

  15. High concentrations of antibodies to xanthine oxidase in human and animal sera. Molecular characterization.

    Science.gov (United States)

    Bruder, G; Jarasch, E D; Heid, H W

    1984-09-01

    The widespread occurrence of antibodies (IgG) specific to xanthine oxidase in both normal (nonimmune) human and animal sera, and in antisera raised against a diversity of unrelated antigens is described. A study of sera from 81 humans revealed that xanthine oxidase-specific IgG represents a high proportion (1-8%) of total IgG. No obvious correlation to pathological events or symptoms of disease could be found. These xanthine oxidase-specific antibodies could be isolated by immunoaffinity chromatography on purified human or bovine xanthine oxidase and showed specific binding to the enzyme polypeptide of Mr 155,000 in immunoblotting experiments. By immunofluorescence microscopy they displayed the same cell type-specific reaction as experimentally induced antibodies, i.e., the staining of lactating mammary gland epithelium and capillary endothelium. The naturally occurring xanthine oxidase-specific antibodies consisted of polyclonal IgG of various subclasses. F(ab')2 preparations gave immune-reactions identical to those of IgG. The human xanthine oxidase-specific IgG cross-reacted with the bovine enzyme and both human and animal antibodies partially inhibited its activity. The xanthine oxidase activity of human milk lipid globules and supernatant fractions from various human tissues was extremely low when compared with that of the bovine antigen. The enzyme protein, however, was effectively precipitated from these sources by both the human and bovine antibodies. We suggest that the exceptionally high concentrations of antibodies against one protein, xanthine oxidase, are due to self-immunization to the xanthine oxidase antigen present in endothelial cells of capillaries. We do not exclude, however, nutritional contributions of bovine milk antigen to the appearance of xanthine oxidase antibodies in human sera. The possible biological functions of this immunological reaction are discussed.

  16. Molluskan Hemocyanins Activate the Classical Pathway of the Human Complement System through Natural Antibodies.

    Science.gov (United States)

    Pizarro-Bauerle, Javier; Maldonado, Ismael; Sosoniuk-Roche, Eduardo; Vallejos, Gerardo; López, Mercedes N; Salazar-Onfray, Flavio; Aguilar-Guzmán, Lorena; Valck, Carolina; Ferreira, Arturo; Becker, María Inés

    2017-01-01

    Molluskan hemocyanins are enormous oxygen-carrier glycoproteins that show remarkable immunostimulatory properties when inoculated in mammals, such as the generation of high levels of antibodies, a strong cellular reaction, and generation of non-specific antitumor immune responses in some types of cancer, particularly for superficial bladder cancer. These proteins have the ability to bias the immune response toward a T h 1 phenotype. However, despite all their current uses with beneficial clinical outcomes, a clear mechanism explaining these properties is not available. Taking into account reports of natural antibodies against the hemocyanin of the gastropod Megathura crenulata [keyhole limpet hemocyanin (KLH)] in humans as well as other vertebrate species, we report here for the first time, the presence, in sera from unimmunized healthy donors, of antibodies recognizing, in addition to KLH, two other hemocyanins from gastropods with documented immunomodulatory capacities: Fisurella latimarginata hemocyanin (FLH) and Concholepas concholepas hemocyanin (CCH). Through an ELISA screening, we found IgM and IgG antibodies reactive with these hemocyanins. When the capacity of these antibodies to bind deglycosylated hemocyanins was studied, no decreased interaction was detected. Moreover, in the case of FLH, deglycosylation increased antibody binding. We evaluated through an in vitro complement deposition assay whether these antibodies activated the classical pathway of the human complement system. The results showed that all three hemocyanins and their deglycosylated counterparts elicited this activation, mediated by C1 binding to immunoglobulins. Thus, this work contributes to the understanding on how the complement system could participate in the immunostimulatory properties of hemocyanins, through natural, complement-activating antibodies reacting with these proteins. Although a role for carbohydrates cannot be completely ruled out, in our experimental setting

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

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    L. Pavlačík

    2007-01-01

    Full Text Available A group of five ferrets vaccinated against the canine distemper virus (CDV was evaluated as to the onset of anti-CDV antibody production and the serum levels of the animals were monitored for one year. The ferrets were immunized with a live attenuated vaccine. The vaccination pattern was as follows: primary vaccination at the age of 6 weeks, fi rst revaccination at 30 days after primary vaccination, and second revaccination after another 30 days. Blood samples were taken prior to primary vaccination and then at 30-day intervals (sampling 1 to 12. The whole experimental cycle covered the period of one year from primary vaccination (till the age of 1 year and 6 weeks. Serum samples were analysed for anti-CDV virus-neutralisation antibodies using a virus-neutralisation test using the Onderstepoort CDV strain. All ferrets had zero virus-neutralisation antibody titres before primary vaccination. Two ferrets produced virus-neutralisation antibodies as a response to first revaccination. A stable antibody level (titre 256 was maintained between months 4 and 11 after primary vaccination and a sudden increase in antibody titre (titres 512 and 1024 - 2048 occurred in both animals in months 11 and 12. The reason for the abrupt rise in antibody titres in the two animals remains unclear. No anti-CDV seroconversion was observed in the three remaining animals. Regarding the results obtained in this study we do not consider commonly recommended vaccination with a live attenuated anti-CDV vaccine as an effective method of antibodies induction against distemper in young ferrets.

  18. Stratification of antibody-positive subjects by antibody level reveals an impact of immunogenicity on pharmacokinetics.

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    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. Dual display: phage selection driven by co-engagement of two targets by two different antibody fragments.

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    Fagète, Séverine; Botas-Perez, Ledicia; Rossito-Borlat, Irène; Adea, Kenneth; Gueneau, Franck; Ravn, Ulla; Rousseau, François; Kosco-Vilbois, Marie; Fischer, Nicolas; Hartley, Oliver

    2017-09-01

    Antibody phage display technology has supported the emergence of numerous therapeutic antibodies. The development of bispecific antibodies, a promising new frontier in antibody therapy, could be facilitated by new phage display approaches that enable pairs of antibodies to be co-selected based on co-engagement of their respective targets. We describe such an approach, making use of two complementary leucine zipper domains that heterodimerize with high affinity. Phagemids encoding a first antibody fragment (scFv) fused to phage coat protein via the first leucine zipper are rescued in bacteria expressing a second scFv fused to the second leucine zipper as a soluble periplasmic protein, so that it is acquired by phage during assembly. Using a soluble scFv specific for a human CD3-derived peptide, we show that its acquisition by phage displaying an irrelevant antibody is sufficiently robust to drive selection of rare phage (1 in 105) over three rounds of panning. We then set up a model selection experiment using a cell line expressing the chemokine receptor CCR5 fused to the CD3 peptide together with a panel of phage clones capable displaying either an anti-CCR5 scFv or an irrelevant antibody, with or without the capacity to acquire the soluble anti-CD3 scFv. In this experiment we showed that rare phage (1 in 105) capable of displaying the two different scFvs can be specifically enriched over four rounds of panning. This approach has the potential to be applied to the identification of pairs of ligands capable of co-engaging two different user-defined targets, which would facilitate the discovery of novel bispecific antibodies. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Engineering bispecific antibodies with defined chain pairing.

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    Krah, Simon; Sellmann, Carolin; Rhiel, Laura; Schröter, Christian; Dickgiesser, Stephan; Beck, Jan; Zielonka, Stefan; Toleikis, Lars; Hock, Björn; Kolmar, Harald; Becker, Stefan

    2017-10-25

    Bispecific IgG-like antibodies can simultaneously interact with two epitopes on the same or on different antigens. Therefore, these molecules facilitate novel modes of action, which cannot be addressed by conventional monospecific IgGs. However, the generation of such antibodies still appears to be demanding due to their specific architecture comprising four different polypeptide chains that need to assemble correctly. This review focusses on different strategies to circumvent this issue or to enforce a correct chain association with a focus on common-chain bispecific antibodies. Copyright © 2017 Elsevier B.V. All rights reserved.