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Sample records for antibodies final progress

  1. Positron tomographic imaging of tumors using monoclonal antibodies. Final progress report, April 15, 1989--October 31, 1995

    Energy Technology Data Exchange (ETDEWEB)

    Zalutsky, M.R.

    1997-02-01

    The overall objective of this research is to develop methods for utilizing positron emission tomography (PET) to increase the clinical potential of radiolabeled monoclonal antibodies (MAbs). Enhancement of MAb tumor localization by hyperthermia also was proposed. Studies were to have been performed with both {sup 18}F and {sup 124}I; however, the lack of its availability (until quite recently) prevented experiments with {sup 124}I. Instead, two additional lines of inquiry were initiated in which they utilized aspects of the radiofluorination chemistries originally developed for MAbs for labeling chemotactic peptides and meta-iodobenzylguanidine (MIBG) analogues with {sup 18}F. This final report summarizes the original specific aims and the main research accomplishments in studies of mouse, dog and human models.

  2. Positron tomographic imaging of tumors using monoclonal antibodies. Final progress report, April 15, 1989--October 31, 1995

    International Nuclear Information System (INIS)

    The overall objective of this research is to develop methods for utilizing positron emission tomography (PET) to increase the clinical potential of radiolabeled monoclonal antibodies (MAbs). Enhancement of MAb tumor localization by hyperthermia also was proposed. Studies were to have been performed with both 18F and 124I; however, the lack of its availability (until quite recently) prevented experiments with 124I. Instead, two additional lines of inquiry were initiated in which they utilized aspects of the radiofluorination chemistries originally developed for MAbs for labeling chemotactic peptides and meta-iodobenzylguanidine (MIBG) analogues with 18F. This final report summarizes the original specific aims and the main research accomplishments in studies of mouse, dog and human models

  3. Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Josef Michl

    2011-10-31

    In this project we have established guidelines for the design on organic chromophores suitable for producing high triplet yields via singlet fission. We have proven their utility by identifying a chromophore of a structural class that had never been examined for singlet fission before, 1,3-diphenylisobenzofuran, and demonstrating in two independent ways that a thin layer of this material produces a triplet yield of 200% within experimental error. We have also designed a second chromophore of a very different type, again of a structural class that had not been examined for singlet fission before, and found that in a thin layer it produces a 70% triplet yield. Finally, we have enhanced the theoretical understanding of the quantum mechanical nature of the singlet fission process.

  4. Final Performance Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Houldin, Joseph [Delaware Valley Industrial Resource Center, Philadelphia, PA (United States); Saboor, Veronica [Delaware Valley Industrial Resource Center, Philadelphia, PA (United States)

    2016-03-30

    about assessing a company’s technical assets, broadening our view of the business to go beyond what they make or what NAICS code they have…to better understand their capacity, capability, and expertise, and to learn more about THEIR customers. Knowing more about the markets they serve can often provide insight into their level of technical knowledge and sophistication. Finally, in the spirit of realizing the intent of the Accelerator we strove to align and integrate the work and activities supported by the five funding agencies to leverage each effort. To that end, we include in the Integrated Work Plan a graphic that illustrates that integration. What follows is our summary report of the project, aggregated from prior reports.

  5. Technological progresses in monoclonal antibody production systems.

    Science.gov (United States)

    Rodrigues, Maria Elisa; Costa, Ana Rita; Henriques, Mariana; Azeredo, Joana; Oliveira, Rosário

    2010-01-01

    Monoclonal antibodies (mAbs) have become vitally important to modern medicine and are currently one of the major biopharmaceutical products in development. However, the high clinical dose requirements of mAbs demand a greater biomanufacturing capacity, leading to the development of new technologies for their large-scale production, with mammalian cell culture dominating the scenario. Although some companies have tried to meet these demands by creating bioreactors of increased capacity, the optimization of cell culture productivity in normal bioreactors appears as a better strategy. This review describes the main technological progresses made with this intent, presenting the advantages and limitations of each production system, as well as suggestions for improvements. New and upgraded bioreactors have emerged both for adherent and suspension cell culture, with disposable reactors attracting increased interest in the last years. Furthermore, the strategies and technologies used to control culture parameters are in constant evolution, aiming at the on-line multiparameter monitoring and considering now parameters not seen as relevant for process optimization in the past. All progresses being made have as primary goal the development of highly productive and economic mAb manufacturing processes that will allow the rapid introduction of the product in the biopharmaceutical market at more accessible prices. PMID:20043321

  6. Technological progresses in monoclonal antibody production systems

    OpenAIRE

    Rodrigues, E.; Costa, A R; Henriques, Mariana; Azeredo, Joana; Oliveira, Rosário

    2009-01-01

    Monoclonal antibodies (mAbs) have become vitally important to modern medicine and are currently one of the major biopharmaceutical products in development. However, the high clinical dose requirements of mAbs demand a greater biomanufacturing capacity, leading to the development of new technologies for their large-scale production, with mammalian cell culture dominating the scenario. Although some companies have tried to meet these demands by creating bioreactors of increased capacity, the op...

  7. IRIS Final Technical Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    M. D. Carelli

    2003-11-03

    OAK-B135 This NERI project, originally started as the Secure Transportable Autonomous Light Water Reactor (STAR-LW) and currently known as the International Reactor Innovative and Secure (IRIS) project, had the objective of investigating a novel type of water-cooled reactor to satisfy the Generation IV goals: fuel cycle sustainability, enhanced reliability and safety, and improved economics. The research objectives over the three-year (1999-2002) program were as follows: First year: Assess various design alternatives and establish main characteristics of a point design; Second year: Perform feasibility and engineering assessment of the selected design solutions; Third year: Complete reactor design and performance evaluation, including cost assessment These objectives were fully attained and actually they served to launch IRIS as a full fledged project for eventual commercial deployment. The program did not terminate in 2002 at the end of the NERI program, and has just entered in its fifth year. This has been made possible by the IRIS project participants which have grown from the original four member, two-countries team to the current twenty members, nine countries consortium. All the consortium members work under their own funding and it is estimated that the value of their in-kind contributions over the life of the project has been of the order of $30M. Currently, approximately 100 people worldwide are involved in the project. A very important constituency of the IRIS project is the academia: 7 universities from four countries are members of the consortium and five more US universities are associated via parallel NERI programs. To date, 97 students have worked or are working on IRIS; 59 IRIS-related graduate theses have been prepared or are in preparation, and 41 of these students have already graduated with M.S. (33) or Ph.D. (8) degrees. This ''final'' report (final only as far as the NERI program is concerned) summarizes the work performed

  8. B cells and antibodies in progressive multiple sclerosis: Contribution to neurodegeneration and progression.

    Science.gov (United States)

    Fraussen, Judith; de Bock, Laura; Somers, Veerle

    2016-09-01

    Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination, axonal degeneration and gliosis. The progressive form of MS is an important research topic as not much is known about its underlying mechanisms and no therapy is available. Although progressive MS is traditionally considered to be driven by neurodegeneration, compartmentalized CNS inflammation is currently accepted as one of the driving processes behind neurodegeneration and progression. In this review, the involvement of B cells and antibodies in progressive MS is discussed. The identification of meningeal ectopic B cell follicles in secondary progressive MS (SPMS) patients and the successful use of B cell-depleting therapy in primary progressive MS (PPMS) patients have underlined the importance of B cells in progressive MS. Proof is also available for the role of antibodies in neurodegeneration and progression in MS. Here, oligoclonal immunoglobulin M (IgM) production and autoreactive antibodies are described, with a focus on antibodies directed against sperm-associated antigen 16 (SPAG16). Further research into the role of B cells and autoantibodies in MS progression can lead to novel prognostic and theranostic opportunities.

  9. 1995 PVUSA progress report. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-03-01

    Photovoltaics for Utility Scale Applications (PVUSA) is a national public-private partnership that is assessing and demonstrating the viability of utility-scale (US) photovoltaic (PV) electric generation systems and recent developments in PV module technology. This report updates the project`s progress, reviews the status and performance of the various PV installations during 1995, summarizes key accomplishments and conclusions, and serves as the final report under Pacific Gas and Electric Company`s project management.

  10. Antiphospholipid antibodies predict progression of abdominal aortic aneurysms.

    Directory of Open Access Journals (Sweden)

    Christina Duftner

    Full Text Available Antiphospholipid antibodies (aPLs frequently occur in autoimmune and cardiovascular diseases and correlate with a worse clinical outcome. In the present study, we evaluated the association between antiphospholipid antibodies (aPLs, markers of inflammation, disease progression and the presence of an intra-aneurysmal thrombus in abdominal aortic aneurysm (AAA patients. APLs ELISAs were performed in frozen serum samples of 96 consecutive AAA patients and 48 healthy controls yielding positive test results in 13 patients (13.5% and 3 controls (6.3%; n.s.. Nine of the 13 aPL-positive AAA patients underwent a second antibody testing >12 weeks apart revealing a positive result in 6 cases. APL-positive patients had increased levels of inflammatory markers compared to aPL-negative patients. Disease progression was defined as an increase of the AAA diameter >0.5 cm/year measured by sonography. Follow-up was performed in 69 patients identifying 41 (59.4% patients with progressive disease. Performing multipredictor logistic regression analysis adjusting for classical AAA risk factors as confounders, the presence of aPLs at baseline revealed an odds ratio of 9.4 (95% CI 1.0-86.8, p = 0.049 to predict AAA progression. Fifty-five patients underwent a computed tomography in addition to ultrasound assessment indicating intra-aneurysmal thrombus formation in 82.3%. Median thrombus volume was 46.7 cm3 (1.9-377.5. AAA diameter correlated with the size of the intra-aneurysmal thrombus (corrcoeff = 0.721, p<0.001, however neither the presence nor the size of the intra-aneurysmal thrombus were related to the presence of aPLs. In conclusion, the presence of aPLs is associated with elevated levels of inflammatory markers and is an independent predictor of progressive disease in AAA patients.

  11. High concentration of antimitochondrial antibodies predicts progressive primary biliary cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Robert Flisiak; Maria Pelszynska; Danuta Prokopowicz; Magdalena Rogalska; Urszula Grygoruk

    2005-01-01

    AIM: To evaluate the serum concentration of antimitochondrial antibodies (AMAs) as a prognostic indicator of progressive primary biliary cirrhosis (pPBC).METHODS: Serum concentrations of AMA subtypes (anti-M2, anti-M4, and anti-M9), biochemical indices of liver function and Mayo risk factor (MRF) were determined in 30 women with diagnosed primary biliary cirrhosis (PBC) selected among 348 females with elevated alkaline phosphatase but without signs of hepatic decompensation.They were followed up for 5 years for possible development of hepatic decompensation.RESULTS: Anti-M2 concentration was significantly correlated with bilirubin and albumin levels as well as MRF, whereas anti-M4 was significantly correlated with albumin level, prothrombin time and MRF. During the 5-year follow-up, progressive PBC (pPBC) was diagnosed in 3 among 23 patients available for evaluation. These 3patients were positive for both anti-M2 and anti-M4.Anti-M2 serum concentration exceeded 1 300 RU/mL in patients with pPBC and only in 1 among 20 non-progressive PBC persons (5%). Anti-M4 serum concentration exceeded 400 RU/mL in 2 of the progressive patients and none in the non-progressive group. In contrast, anti-M9 serum concentration was below 100 RU/mL in all patients with pPBC, and higher than 100 RU/mL in 11 women (55%)among the non-progressive group.CONCLUSION: Females with elevated alkaline phosphatase and high anti-M2 and anti-M4 concentrations are at a high risk for developing pPBC. Quantitative AMA detection should be considered as a method for early diagnosis of pPBC.

  12. Neutralizing antibodies in slowly progressing HIV-1 infection

    DEFF Research Database (Denmark)

    Schønning, Kristian; Nielsen, C; Iversen, Johan;

    1995-01-01

    Ten asymptomatic individuals who had experienced only limited CD4+ cell loss after prolonged infection with HIV-1 were studied. These individuals had a mean CD4+ cell count of 674 x 10(6) cells/L and a mean duration of infection of 8.5 years. Also included were 10 asymptomatic HIV-1-infected...... with SPI generally neutralized the contemporaneous isolate, whereas serum from individuals with RPI did not [geometric mean antibody titer (GMT), 45 vs. 3; p = 0.0047]. There was no difference in neutralizing ability against HIVMN (GMT,2,593 vs. 2,263; p = 0.74) and only a small difference against HIVIIIB...... (GMT, 115 vs. 50; p = 0.075). Our results indicate that individuals with SPI are characterized by an ability to neutralize their own HIV strain.(ABSTRACT TRUNCATED AT 250 WORDS)...

  13. SPECT assay of radiolabeled monoclonal antibodies. Progress report, September 1, 1992--August 24, 1993

    Energy Technology Data Exchange (ETDEWEB)

    Jaszczak, R.J.

    1993-08-20

    The overall goal of this project is to improve the effectiveness of single photon emission computed tomography (SPECT) to image and quantify radiolabeled monoclonal antibodies. During the past year, we have made significant progress toward this goal, and this report summarizes that work. Our efforts have been mainly directed along three fronts. First, we have developed and tested new reconstruction methods including three-dimensional iterative algorithms that model non-uniform attenuation and distance-dependent detector response. Both fan beam and parallel beam collimator geometries have been modeled and novel ways of improving the efficiency of the computationally intensive methods have been introduced. Second, an ultra-high resolution, small field-of-view pinhole collimator has been constructed and evaluated. Reconstructed spatial resolution of 1 to 3 mm (FWHM) has been achieved in phantom scans with a useful field-of-view of 9 to 10 cm. Finally, we have investigated the ability of SPECT to image and quantify astatine-211 distributions. Reconstructed images of phantom data demonstrated quantitative accuracy to within 10% with proper attenuation and scatter compensation.

  14. Comparative study of antibodies that are associated with disease progression in HIV disease.

    Science.gov (United States)

    Tóth, F D; Süsal, C; Ujhelyi, E; Bánhegyi, D; Kiss, J; Daniel, V; Nagy, I; Opelz, G; Füst, G

    1994-06-01

    Two types of antibodies which previously were found to be inversely associated with CD4+ cell counts and which may contribute to the progression of HIV disease were measured in parallel in 55 serum samples of 7 longitudinally tested HIV-infected patients (4 homosexual men, 3 haemophilic men) and in 15 serum samples from 15 patients with advanced AIDS. HIV-infection enhancing antibodies were determined in the presence of near-physiologic human complement concentration using a complement receptor type 2 (CR2) carrying HIV-target cell line. IgG and IgA class autoantibodies directed against human IgG-Fab fragments were measured in specific ELISA assays. In agreement with our previous studies obtained in HIV-seropositive haemophilic patients, significant negative correlations were found between CD4+ cell counts and IgG anti-Fab and IgA anti-Fab antibodies (Spearman correlation coefficient r = -0.587, P < 0.0001; and r = -0.269, P = 0.024, respectively). A significant positive correlation was observed between complement-dependent enhancing antibodies and IgA anti-Fab antibodies (r = 0.408, P = 0.003), whereas the correlation with IgG anti-Fab antibodies was only weak (r = 0.288, P = 0.034). Serum samples with high titres of complement-dependent enhancing antibodies had almost 3 times higher IgA anti-Fab autoantibody activity than sera with low titres (P = 0.0038). Our findings indicate that the two disease markers in HIV disease, enhancing antibodies and autoantibodies directed against the Fab moiety of IgG, are not identical. However, anti-Fab antibodies may contribute to complement-dependent HIV infection enhancement. PMID:7959901

  15. Progress in the development of therapeutic antibodies targeting prion proteins and β-amyloid peptides

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Prion diseases and Alzheimer’s disease (AD) are characterized by protein misfolding, and can lead to dementia. However, prion diseases are infectious and transmissible, while AD is not. The similarities and differences between these diseases have led researchers to perform comparative studies. In the last 2 decades, progress has been made in immunotherapy using anti-prion protein and anti-β-amyloid antibodies. In this study, we review new ideas and strategies for therapeutic antibodies targeting prion diseases and AD through conformation dependence.

  16. Serum DHCR24 Auto-antibody as a new Biomarker for Progression of Hepatitis C

    OpenAIRE

    Sayeh Ezzikouri; Kiminori Kimura; Hajime Sunagozaka; Shuichi Kaneko; Kazuaki Inoue; Tomohiro Nishimura; Tsunekazu Hishima; Michinori Kohara; Kyoko Tsukiyama-Kohara

    2015-01-01

    Background: New biomarkers are needed to identify the stage of hepatitis C virus (HCV)-infected diseases in order to reduce the mortality rates. Herein, we investigated whether serum 3β-hydroxysterol Δ24-reductase antibody (DHCR24 Ab) may serve as a prognostic marker for hepatitis C infection progression to hepatocellular carcinoma (HCC). Methods: Serum DHCR24 Abs from 395 HCV-positive patients, including 133 chronic hepatitis (CHC), 85 liver cirrhosis (LCC), and 177 HCC (HCC-C) patients; ...

  17. Utilizing poxviral vectored vaccines for antibody induction-progress and prospects.

    Science.gov (United States)

    Draper, Simon J; Cottingham, Matthew G; Gilbert, Sarah C

    2013-09-01

    Over the last decade, poxviral vectors emerged as a mainstay approach for the induction of T cell-mediated immunity by vaccination, and their suitability for human use has led to widespread clinical testing of candidate vectors against infectious intracellular pathogens and cancer. In contrast, poxviruses have been widely perceived in the vaccine field as a poor choice of vector for the induction of humoral immunity. However, a growing body of data, from both animal models and recent clinical trials, now suggests that these vectors can be successfully utilized to prime and boost B cells and effective antibody responses. Significant progress has been made in the context of heterologous prime-boost immunization regimes, whereby poxviruses are able to boost responses primed by other vectors, leading to the induction of high-titre antigen-specific antibody responses. In other cases, poxviral vectors have been shown to stimulate humoral immunity against both themselves and encoded transgenes, in particular viral surface proteins such as influenza haemagglutinin. In the veterinary field, recombinant poxviral vectors have made a significant impact with numerous vectors licensed for use against a variety of animal viruses. On-going studies continue to explore the potential of poxviral vectors to modulate qualitative aspects of the humoral response, as well as their amenability to adjuvantation seeking to improve quantitative antibody immunogenicity. Nevertheless, the underlying mechanisms of B cell induction by recombinant poxviruses remain poorly defined, and further work is necessary to help guide the rational optimization of future poxviral vaccine candidates aiming to induce antibodies. PMID:23746455

  18. Chronic lymphocytic leukemia patients have a preserved cytomegalovirus-specific antibody response despite progressive hypogammaglobulinemia.

    Science.gov (United States)

    Vanura, Katrina; Rieder, Franz; Kastner, Marie-Theres; Biebl, Julia; Sandhofer, Michael; Le, Trang; Strassl, Robert; Puchhammer-Stöckl, Elisabeth; Perkmann, Thomas; Steininger, Christoph F; Stamatopoulos, Kostas; Graninger, Wolfgang; Jäger, Ulrich; Steininger, Christoph

    2013-01-01

    Chronic lymphocytic leukemia (CLL) is characterized by progressive hypogammaglobulinemia predisposing affected patients to a variety of infectious diseases but paradoxically not to cytomegalovirus (CMV) disease. Moreover, we found reactivity of a panel of CLL recombinant antibodies (CLL-rAbs) encoded by a germ-line allele with a single CMV protein, pUL32, despite differing antibody binding motifs. To put these findings into perspective, we studied prospectively relative frequency of viremia, kinetics of total and virus-specific IgG over time, and UL32 genetic variation in a cohort of therapy-naive patients (n=200). CMV-DNA was detected in 3% (6/200) of patients. The decay of total IgG was uniform (mean, 0.03; SD, 0.03) and correlated with that of IgG subclasses 1-4 in the paired samples available (n=64; p<0.001). Total CMV-specific IgG kinetics were more variable (mean, 0,02; SD, 0,06) and mean decay values differed significantly from those of total IgG (p=0.034). Boosts of CMV-specific antibody levels were observed in 49% (22/45) of CMV-seropositive patients. In contrast, VZV- and EBV-specific IgG levels decayed in parallel with total IgG levels (p=0.003 and p=0.001, respectively). VZV-specific IgG even became undetectable in 18% (9/50) of patients whereas CMV-specific ones remained detectable in all seropositive patients. The observed CMV-specific IgG kinetics were predicated upon the highly divergent kinetics of IgG specific for individual antigens - glycoprotein B-specific IgG were boosted in 51% and pUL32-specific IgG in 32% of patients. In conclusion, CLL patients have a preserved CMV-specific antibody response despite progressive decay of total IgG and IgG subclasses. CMV-specific IgG levels are frequently boosted in contrast to that of other herpesviruses indicative of a higher rate of CMV reactivation and antigen-presentation. In contrast to the reactivity of multiple different CLL-rAbs with pUL32, boosts of humoral immunity are triggered apparently by

  19. Chronic lymphocytic leukemia patients have a preserved cytomegalovirus-specific antibody response despite progressive hypogammaglobulinemia.

    Directory of Open Access Journals (Sweden)

    Katrina Vanura

    Full Text Available Chronic lymphocytic leukemia (CLL is characterized by progressive hypogammaglobulinemia predisposing affected patients to a variety of infectious diseases but paradoxically not to cytomegalovirus (CMV disease. Moreover, we found reactivity of a panel of CLL recombinant antibodies (CLL-rAbs encoded by a germ-line allele with a single CMV protein, pUL32, despite differing antibody binding motifs. To put these findings into perspective, we studied prospectively relative frequency of viremia, kinetics of total and virus-specific IgG over time, and UL32 genetic variation in a cohort of therapy-naive patients (n=200. CMV-DNA was detected in 3% (6/200 of patients. The decay of total IgG was uniform (mean, 0.03; SD, 0.03 and correlated with that of IgG subclasses 1-4 in the paired samples available (n=64; p<0.001. Total CMV-specific IgG kinetics were more variable (mean, 0,02; SD, 0,06 and mean decay values differed significantly from those of total IgG (p=0.034. Boosts of CMV-specific antibody levels were observed in 49% (22/45 of CMV-seropositive patients. In contrast, VZV- and EBV-specific IgG levels decayed in parallel with total IgG levels (p=0.003 and p=0.001, respectively. VZV-specific IgG even became undetectable in 18% (9/50 of patients whereas CMV-specific ones remained detectable in all seropositive patients. The observed CMV-specific IgG kinetics were predicated upon the highly divergent kinetics of IgG specific for individual antigens - glycoprotein B-specific IgG were boosted in 51% and pUL32-specific IgG in 32% of patients. In conclusion, CLL patients have a preserved CMV-specific antibody response despite progressive decay of total IgG and IgG subclasses. CMV-specific IgG levels are frequently boosted in contrast to that of other herpesviruses indicative of a higher rate of CMV reactivation and antigen-presentation. In contrast to the reactivity of multiple different CLL-rAbs with pUL32, boosts of humoral immunity are triggered

  20. SPECT assay of radiolabeled monoclonal antibodies. Comprehensive progress report, September 1989--February 1992

    Energy Technology Data Exchange (ETDEWEB)

    Jaszczak, R.J.

    1992-02-01

    The long-term goal of this research project is to develop methods to improve the utility of single photon emission computed tomography (SPECI) to quantify the biodistribution of monoclonal antibodies (MoAbs) labeled with clinically relevant radionuclides ({sup 123}I, {sup 131}I, and {sup 111}In) and with another radionuclide,{sup 211}At, recently used in therapy. We describe here our progress in developing quantitative SPECT methodology for {sup 111}In and {sup 123}I. We have focused our recent research thrusts on the following aspects of SPECT: (1) The development of improved SPECT hardware, such as improved acquisition geometries. (2) The development of better reconstruction methods that provide accurate compensation for the physical factors that affect SPECT quantification. (3) The application of carefully designed simulations and experiments to validate our hardware and software approaches.

  1. Broadly neutralizing human monoclonal JC polyomavirus VP1-specific antibodies as candidate therapeutics for progressive multifocal leukoencephalopathy.

    Science.gov (United States)

    Jelcic, Ivan; Combaluzier, Benoit; Jelcic, Ilijas; Faigle, Wolfgang; Senn, Luzia; Reinhart, Brenda J; Ströh, Luisa; Nitsch, Roger M; Stehle, Thilo; Sospedra, Mireia; Grimm, Jan; Martin, Roland

    2015-09-23

    In immunocompromised individuals, JC polyomavirus (JCPyV) may mutate and gain access to the central nervous system resulting in progressive multifocal leukoencephalopathy (PML), an often fatal opportunistic infection for which no treatments are currently available. Despite recent progress, the contribution of JCPyV-specific humoral immunity to controlling asymptomatic infection throughout life and to eliminating JCPyV from the brain is poorly understood. We examined antibody responses against JCPyV major capsid protein VP1 (viral protein 1) variants in the serum and cerebrospinal fluid (CSF) of healthy donors (HDs), JCPyV-positive multiple sclerosis patients treated with the anti-VLA-4 monoclonal antibody natalizumab (NAT), and patients with NAT-associated PML. Before and during PML, CSF antibody responses against JCPyV VP1 variants show "recognition holes"; however, upon immune reconstitution, CSF antibody titers rise, then recognize PML-associated JCPyV VP1 variants, and may be involved in elimination of the virus. We therefore reasoned that the memory B cell repertoire of individuals who recovered from PML could be a source for the molecular cloning of broadly neutralizing antibodies for passive immunization. We generated a series of memory B cell-derived JCPyV VP1-specific human monoclonal antibodies from HDs and a patient with NAT-associated PML-immune reconstitution inflammatory syndrome (IRIS). These antibodies exhibited diverse binding affinity, cross-reactivity with the closely related BK polyomavirus, recognition of PML-causing VP1 variants, and JCPyV neutralization. Almost all antibodies with exquisite specificity for JCPyV, neutralizing activity, recognition of all tested JCPyV PML variants, and high affinity were derived from one patient who had recovered from PML. These antibodies are promising drug candidates for the development of a treatment of PML. PMID:26400911

  2. Theoretical analysis of excipient concentrations during the final ultrafiltration/diafiltration step of therapeutic antibody.

    Science.gov (United States)

    Miao, Fudu; Velayudhan, Ajoy; DiBella, Elsie; Shervin, Jaclyn; Felo, Michael; Teeters, Mark; Alred, Patricia

    2009-01-01

    Diafiltration of a protein solution into a new buffer is a common final step in biopharmaceutical manufacturing. However, the excipient concentrations in the retentate are not always equal to their corresponding concentrations in the new buffer (diafiltration buffer). This phenomenon was observed repeatedly during diafiltration of different therapeutic monoclonal antibodies in which the concentrations of histidine and either sorbitol or sucrose (depending on which was chosen for the diafiltration buffer) in the retentate were lower than in the diafiltration buffer. Experimental studies and theoretical analyses of the ultrafiltration/diafiltration (UF/DF) step were carried out to determine the primary causes of the phenomenon and to develop a mathematical model capable of predicting retentate excipient concentrations. The analyses showed that retentate histidine concentration was low primarily because of repulsive charge interactions between positively-charged histidine molecules and positively-charged protein molecules, and that volume exclusion effects were secondary for like-charged molecules. The positively-charged protein molecules generate an electrical potential that cause an uneven distribution of charged histidine molecules. This interaction was used to construct a mathematical model based on the Poisson-Boltzmann equation. The model successfully predicted the final histidine concentration in the diafiltered product (retentate) from the UF/DF development and production runs, with good agreement across a wide range of protein and histidine concentrations for four therapeutic monoclonal antibodies. The concentrations of uncharged excipients (sorbitol or sucrose) were also successfully predicted using previously established models, with volume exclusion identified as the primary cause of differences in uncharged excipient concentrations in the retentate and diafiltration buffer.

  3. Association of progressive CD4(+ T cell decline in SIV infection with the induction of autoreactive antibodies.

    Directory of Open Access Journals (Sweden)

    Takeo Kuwata

    2009-04-01

    Full Text Available The progressive decline of CD4(+ T cells is a hallmark of disease progression in human immunodeficiency virus (HIV and simian immunodeficiency virus (SIV infection. Whereas the acute phase of the infection is dominated by virus-mediated depletion of memory CD4(+ T cells, chronic infection is often associated with a progressive decline of total CD4(+ T cells, including the naïve subset. The mechanism of this second phase of CD4(+ T cell loss is unclear and may include immune activation-induced cell death, immune-mediated destruction, and regenerative or homeostatic failure. We studied patterns of CD4(+ T cell subset depletion in blood and tissues in a group of 20 rhesus macaques inoculated with derivatives of the pathogenic SIVsmE543-3 or SIVmac239. Phenotypic analysis of CD4(+ T cells demonstrated two patterns of CD4(+ T cell depletion, primarily affecting either naïve or memory CD4(+ T cells. Progressive decline of total CD4(+ T cells was observed only in macaques with naïve CD4(+ T cell depletion (ND, though the depletion of memory CD4(+ T cells was profound in macaques with memory CD4(+ T cell depletion (MD. ND macaques exhibited lower viral load and higher SIV-specific antibody responses and greater B cell activation than MD macaques. Depletion of naïve CD4(+ T cells was associated with plasma antibodies autoreactive with CD4(+ T cells, increasing numbers of IgG-coated CD4(+ T cells, and increased incidence of autoreactive antibodies to platelets (GPIIIa, dsDNA, and phospholipid (aPL. Consistent with a biological role of these antibodies, these latter antibodies were accompanied by clinical features associated with autoimmune disorders, thrombocytopenia, and catastrophic thrombotic events. More importantly for AIDS pathogenesis, the level of autoreactive antibodies significantly correlated with the extent of naïve CD4(+ T cell depletion. These results suggest an important role of autoreactive antibodies in the CD4(+ T cell decline

  4. Recent progress of diagnostic and therapeutic approach to cancers using polyclonal or monoclonal antibodies

    International Nuclear Information System (INIS)

    Among the major topics of interest in cancer immunology, immunodiagnosis and immunotherapy with the antibodies are summarized historically and prospectively. The concept of injecting anti-tumor cell antibodies to localize tumors was first introduced in experimental systems by Pressman (1957). Since then, various trials have been achieved with human tumors using specific or nonspecific tumor-localizing antibodies diagnostically or therapeutically. In 1970's, successes in immunodiagnosis with the antibodies to oncofetal proteins also have been reported. Recently, there are numerous papers dealed with a series of external scanning or serotherapeutic trials by the use of monoclonal antibodies that bind selectively to tumor cells. Various relevant problems with them are discussed. (author)

  5. Solid state NMR coal science. Final progress report

    Energy Technology Data Exchange (ETDEWEB)

    Zilm, K.W.

    1986-08-01

    This report covers the final work on this project and summarizes the accomplishments of the project. The dipolar shift correlated 2D NMR method described in previous reports has been applied to a whole coal successfully. The theory necessary for semi-quantitative interpretation of this data has also been worked out and implemented computationally. Several interesting structural features in coal seen by the 2D dipolar shift experiment not previously observed by other NMR methods are discussed. 4 figs.

  6. Research Progress in Monoclonal Antibodies%单克隆抗体研究进展

    Institute of Scientific and Technical Information of China (English)

    刘萍; 陈苗苗; 刘学荣; 牟克斌; 黄银君

    2012-01-01

    Hybridization techniques have made mouse monoclonal antibody widely use in diagnosis and research of human disease, and established the first milestone of therapeutic antibody. With the biology development and antibody genetic structure clarification, people can humanize mouse antibody with DNA recombination and antibody library which developed antibody techniques from chimeric and reshaped to human antibody. Both humanized monoclonal antibody and its derivative overcome the clinical shortage of mouse antibody from different angles, also bring a new dawn to made antibody.%杂交瘤技术使鼠源单克隆抗体被广泛用于人类疾病的诊断和研究,建立了治疗性抗体的第一个里程碑.随着生物学技术的发展和抗体基因结构的阐明,应用DNA重组技术和抗体库技术对鼠单抗进行人源化改造,先后出现了嵌合抗体、人源化抗体和全人抗体,它们从不同角度克服了鼠单抗临床应用的不足,使抗体制备技术进入了一个全新的时代.

  7. Novel antibody conjugates for enhanced tumor uptake. Final report, September 1, 1992--August 31, 1997

    International Nuclear Information System (INIS)

    Progress in three areas of research is summarized. These are as follows: Labeling Monoclonal antibodies (MAbs) with Tc-99m and Re-186; human melanoma tumors and specific MAbs; evaluation of biological response modifiers (BRM). The techniques of labeling MAbs (IgM, IgG, F(ab')2 or F(ab')) with Tc-99m was developed in the author's laboratory in 1989 and that with Re-186 in 1992. The techniques are in daily use in the laboratory since then and are adapted to a convenient kit formulation. The metal ions are bound at MAb sulfhydryls generated by a controlled reduction of a pair of disulfide groups. At least two types of MAbs labeled with Tc-99m by this method have been administered into patients and excellent diagnostic results have been obtained. Over the past two and a half years the author has been successfully growing human melanoma tumors in athymic Balb/c nude mice. The cell LINE, WM-9, was obtained from Dr. D Herlyn's laboratory at Wistar Institute in Philadelphia. Sufficient quantities of antihuman melanoma specific antibodies ME 31.3 (Wistar, IgG-1) and MEM-136 (Hybritech, IgG-2A) and their F(ab')2 fragments are also available in the laboratory. The use of BRM is a rapidly evolving field. Over the past four years, the author has evaluated a number of BRMs in a quest for agents that may augment MAb tumor uptake. These included interferon-α; a pokeweed mitogen and Ukrain, an alkaloid separated from a plant Chelideonium Majis. In these preliminary studies, normal Balb/c mice were used and the BRMs were given i.p. one hour prior to the i.v. administration of tumor necrosis factor or an MAb (TNT-F(ab')2) labeled with Tc-99m which served as an imaging agent. Animals were sacrificed at 1.5 hr or 4 hrs post-injection. Highlights of the work are given here in a table

  8. Novel antibody conjugates for enhanced tumor uptake. Final report, September 1, 1992--August 31, 1997

    Energy Technology Data Exchange (ETDEWEB)

    Thakur, M.

    1997-12-31

    Progress in three areas of research is summarized. These are as follows: Labeling Monoclonal antibodies (MAbs) with Tc-99m and Re-186; human melanoma tumors and specific MAbs; evaluation of biological response modifiers (BRM). The techniques of labeling MAbs (IgM, IgG, F(ab{prime}){sub 2} or F(ab{prime})) with Tc-99m was developed in the author`s laboratory in 1989 and that with Re-186 in 1992. The techniques are in daily use in the laboratory since then and are adapted to a convenient kit formulation. The metal ions are bound at MAb sulfhydryls generated by a controlled reduction of a pair of disulfide groups. At least two types of MAbs labeled with Tc-99m by this method have been administered into patients and excellent diagnostic results have been obtained. Over the past two and a half years the author has been successfully growing human melanoma tumors in athymic Balb/c nude mice. The cell LINE, WM-9, was obtained from Dr. D Herlyn`s laboratory at Wistar Institute in Philadelphia. Sufficient quantities of antihuman melanoma specific antibodies ME 31.3 (Wistar, IgG-1) and MEM-136 (Hybritech, IgG-2A) and their F(ab{prime}){sub 2} fragments are also available in the laboratory. The use of BRM is a rapidly evolving field. Over the past four years, the author has evaluated a number of BRMs in a quest for agents that may augment MAb tumor uptake. These included interferon-{alpha}; a pokeweed mitogen and Ukrain, an alkaloid separated from a plant Chelideonium Majis. In these preliminary studies, normal Balb/c mice were used and the BRMs were given i.p. one hour prior to the i.v. administration of tumor necrosis factor or an MAb (TNT-F(ab{prime}){sub 2}) labeled with Tc-99m which served as an imaging agent. Animals were sacrificed at 1.5 hr or 4 hrs post-injection. Highlights of the work are given here in a table.

  9. Amended Final Report - Antibodies to Radionuclides. Engineering by Surface Display for Immunosensors

    Energy Technology Data Exchange (ETDEWEB)

    Blake, Diane A. [Tulane Univ., New Orleans, LA (United States)

    2013-06-14

    The relatively new techniques of antibody display, which permit molecular engineering of antibody structure and function, have the potential to revolutionize the way scientists generate binding proteins for specific applications. However, the skills required to efficiently use antibody display techniques have proven difficult for other laboratories to acquire without hands-on training and exchange of laboratory personnel. This research project is designed bring important expertise in antibody display to the State of Louisiana while pursuing a project with direct relevance to the DOE’s EM program.

  10. Final Progress Report for Ionospheric Dusty Plasma In the Laboratory [Smokey Plasma

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, Scott [Professor

    2010-09-28

    “Ionospheric Dusty Plasma in the Laboratory” is a research project with the purpose of finding and reproducing the characteristics of plasma in the polar mesosphere that is unusually cold (down to 140 K) and contains nanometer-sized dust particles. This final progress report summarizes results from four years of effort that include a final year with a no-cost extension.

  11. 1993 annual final progress report: July 1992 through June 1993

    Energy Technology Data Exchange (ETDEWEB)

    Rohatgi, A.; Crotty, G.; Chen, Z.; Sana, P.; Salami, J.; Doolittle, A.; Pang, A.; Pham, T. [Georgia Inst. of Tech., Atlanta, GA (United States). School of Electrical and Computer Engineering

    1994-11-01

    This is the first annual report since the Inauguration of the University Center of Excellence for Photovoltaics Research and Development (UCEP) at Georgia Tech. The essential objective of the Center is to improve the fundamental understanding of the science and technology of advanced PV devices and materials, to provide training and enrich the educational experience of students in the field, and to increase US competitiveness by providing guidelines to industry and DOE for achieving cost-effective and high efficiency PV devices. These objectives are to be accomplished through a combination of research and education. This report summarizes the technical accomplishments, including modeling, processing, and characterization of cast multicrystalline silicon solar cells; use of modeling and PCD measurements to develop a road map for progressing toward 20% multicrystalline and 25% single crystalline cells; the development of a novel PECVD SiN/SiO{sub 2} AR coating that also provides good surface passivation; PECVD deposited SiO{sub 2} films with record low S and D{sub it} at the SiO{sub 2}/Si interface; and educational activities and accomplishments.

  12. IRIS International Reactor Innovative and Secure Final Technical Progress Report

    International Nuclear Information System (INIS)

    OAK-B135 This NERI project, originally started as the Secure Transportable Autonomous Light Water Reactor (STAR-LW) and currently known as the International Reactor Innovative and Secure (IRIS) project, had the objective of investigating a novel type of water-cooled reactor to satisfy the Generation IV goals: fuel cycle sustainability, enhanced reliability and safety, and improved economics. The research objectives over the three-year (1999-2002) program were as follows: First year: Assess various design alternatives and establish main characteristics of a point design; Second year: Perform feasibility and engineering assessment of the selected design solutions; Third year: Complete reactor design and performance evaluation, including cost assessment These objectives were fully attained and actually they served to launch IRIS as a full fledged project for eventual commercial deployment. The program did not terminate in 2002 at the end of the NERI program, and has just entered in its fifth year. This has been made possible by the IRIS project participants which have grown from the original four member, two-countries team to the current twenty members, nine countries consortium. All the consortium members work under their own funding and it is estimated that the value of their in-kind contributions over the life of the project has been of the order of $30M. Currently, approximately 100 people worldwide are involved in the project. A very important constituency of the IRIS project is the academia: 7 universities from four countries are members of the consortium and five more US universities are associated via parallel NERI programs. To date, 97 students have worked or are working on IRIS; 59 IRIS-related graduate theses have been prepared or are in preparation, and 41 of these students have already graduated with M.S. (33) or Ph.D. (8) degrees. This ''final'' report (final only as far as the NERI program is concerned) summarizes the work performed in the first four

  13. Advanced Fuel Cycle Initiative University Fellowship Program. Final Progress Report

    International Nuclear Information System (INIS)

    2004-2011 Final Report for AFCI University Fellowship Program. The goal of this effort was to be supportive of university students and university programs - particularly those students and programs that will help to strengthen the development of nuclear-related fields. The program also supported the stability of the nuclear infrastructure and developed research partnerships that are helping to enlarge the national nuclear science technology base. In this fellowship program, the U.S. Department of Energy sought master's degree students in nuclear, mechanical, or chemical engineering, engineering/applied physics, physics, chemistry, radiochemistry, or fields of science and engineering applicable to the AFCI/Gen IV/GNEP missions in order to meet future U.S. nuclear program needs. The fellowship program identified candidates and selected full time students of high-caliber who were taking nuclear courses as part of their degree programs. The DOE Academic Program Managers encouraged fellows to pursue summer internships at national laboratories and supported the students with appropriate information so that both the fellows and the nation's nuclear energy objectives were successful.

  14. Verification of Steelmaking Slags Iron Content Final Technical Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    J.Y. Hwang

    2006-10-04

    The steel industry in the United States generates about 30 million tons of by-products each year, including 6 million tons of desulfurization and BOF/BOP slag. The recycling of BF (blast furnace) slag has made significant progress in past years with much of the material being utilized as construction aggregate and in cementitious applications. However, the recycling of desulfurization and BOF/BOP slags still faces many technical, economic, and environmental challenges. Previous efforts have focused on in-plant recycling of the by-products, achieving only limited success. As a result, large amounts of by-products of various qualities have been stockpiled at steel mills or disposed into landfills. After more than 50 years of stockpiling and landfilling, available mill site space has diminished and environmental constraints have increased. The prospect of conventionally landfilling of the material is a high cost option, a waste of true national resources, and an eternal material liability issue. The research effort has demonstrated that major inroads have been made in establishing the viability of recycling and reuse of the steelmaking slags. The research identified key components in the slags, developed technologies to separate the iron units and produce marketable products from the separation processes. Three products are generated from the technology developed in this research, including a high grade iron product containing about 90%Fe, a medium grade iron product containing about 60% Fe, and a low grade iron product containing less than 10% Fe. The high grade iron product contains primarily metallic iron and can be marketed as a replacement of pig iron or DRI (Direct Reduced Iron) for steel mills. The medium grade iron product contains both iron oxide and metallic iron and can be utilized as a substitute for the iron ore in the blast furnace. The low grade iron product is rich in calcium, magnesium and iron oxides and silicates. It has a sufficient lime value and

  15. Anti-Glycine Receptor Antibody Mediated Progressive Encephalomyelitis with Rigidity and Myoclonus Associated with Breast Cancer

    Directory of Open Access Journals (Sweden)

    Sofie N. De Blauwe

    2013-01-01

    Full Text Available We describe a 66-year-old woman who presented with a dramatic course of PERM. Anti-glycine receptor antibodies were found. She stabilized after plasma-exchange and partly recovered. Eighteen months later, a diagnosis of smouldering breast cancer with bone marrow metastasis was made. There are indications that this tumor was already present at first presentation. An overview of PERM and anti-glycine receptor antibodies is given.

  16. Human oxidation-specific antibodies reduce foam cell formation and atherosclerosis progression

    DEFF Research Database (Denmark)

    Tsimikas, Sotirios; Miyanohara, Atsushi; Hartvigsen, Karsten;

    2011-01-01

    We sought to assess the in vivo importance of scavenger receptor (SR)-mediated uptake of oxidized low-density lipoprotein (OxLDL) in atherogenesis and to test the efficacy of human antibody IK17-Fab or IK17 single-chain Fv fragment (IK17-scFv), which lacks immunologic properties of intact antibod...... antibodies other than the ability to inhibit uptake of OxLDL by macrophages, to inhibit atherosclerosis....

  17. Chemoradiotherapy of cancer using boronated monoclonal antibodies. Progress report, December 1, 1982-November 30, 1983

    International Nuclear Information System (INIS)

    The feasibility was established of using antibodies for the delivery of 10B. Problems faced included 1) preservation of antibody activity following boronation, 2) antigenic receptor site density of the target cells, and 3) delivery of a critical number of 10B atoms per cell. The linkage of a heavily boronated polymeric species to antibody by means of a single functional group allow for the delivery of a large number 10B atoms per antibody molecule without a significant reduction in affinity. Both the polyclonally derived anti-thymocyte globulin (ATG) and the monoclonal anti-colorectal carcinoma antibody (17-1A) recognize antigens that are expressed with a density of approximately 106 epitopes per cell. The major concept that we advance is that just as effective cancer chemotherapy is based on the use of a combination of drugs, similarly a combination of compounds could be employed to deliver the requisite amount of 10B to tumor target cells. This could include compounds such as Na2B12H11Sh together with boronated antibodies directed against tumor associated antigens. (DT)

  18. Long-lasting CCR5 internalization by antibodies in a subset of long-term nonprogressors: a possible protective effect against disease progression

    Science.gov (United States)

    Pastori, Claudia; Weiser, Barbara; Barassi, Claudia; Uberti-Foppa, Caterina; Ghezzi, Silvia; Longhi, Renato; Calori, Giliola; Burger, Harold; Kemal, Kimdar; Poli, Guido; Lazzarin, Adriano; Lopalco, Lucia

    2006-01-01

    Exposure to HIV-1 does not necessarily result in infection and progression toward disease, thus suggesting that the control of viral infection may be achieved. Antibodies to CCR5 have been detected in HIV-exposed but uninfected subjects (ESNs); thus, these antibodies could be involved in HIV protection. To assess whether anti-CCR5 antibodies may also contribute to slow HIV disease progression, we searched for anti-CCR5 antibodies in 497 subjects, including 85 long-term nonprogressors (LTNPs), 70 progressors, 135 HIV+ patients treated with highly active antiretroviral therapy (HAART), and 207 seronegative donors. We found anti-CCR5 antibodies in a fraction of the LTNPs(23.5%) but not in the other populations studied (P < .001). These antibodies recognized a conformational epitope within the first extramembrane loop of CCR5, and they induced a stable and long-lasting downregulation of CCR5 on the surface of T lymphocytes, which inhibited HIV entry. In addition, CD4+ lymphocytes from LTNPs having anti-CCR5 antibodies are resistance to R5 strains of HIV-1. Follow-up studies showed that the loss of anti-CCR5 antibodies occurred in some subjects, and this loss was significantly associated with a progression toward disease, whereas subjects who retained anti-CCR5 Abs maintained their LTNP status. Induction of anti-CCR5 Abs could be relevant to vaccine design and therapeutics. PMID:16522810

  19. Progress in the development of immunoanalytical methods incorporating recombinant antibodies to small molecular weight biotoxins.

    Science.gov (United States)

    Kavanagh, Owen; Elliott, Christopher T; Campbell, Katrina

    2015-04-01

    Rapid immunoanalytical screening of food and environmental samples for small molecular weight (hapten) biotoxin contaminations requires the production of antibody reagents that possess the requisite sensitivity and specificity. To date animal-derived polyclonal (pAb) and monoclonal (mAb) antibodies have provided the binding element of the majority of these assays but recombinant antibodies (rAb) isolated from in vitro combinatorial phage display libraries are an exciting alternative due to (1) circumventing the need for experimental animals, (2) speed of production in commonly used in vitro expression systems and (3) subsequent molecular enhancement of binder performance. Short chain variable fragments (scFv) have been the most commonly employed rAb reagents for hapten biotoxin detection over the last two decades but antibody binding fragments (Fab) and single domain antibodies (sdAb) are increasing in popularity due to increased expression efficiency of functional binders and superior resistance to solvents. rAb-based immunochromatographic assays and surface plasmon resonance (SPR) biosensors have been reported to detect sub-regulatory levels of fungal (mycotoxins), marine (phycotoxins) and aquatic biotoxins in a wide range of food and environmental matrices, however this technology has yet to surpass the performances of the equivalent mAb- and pAb-based formats. As such the full potential of rAb technology in hapten biotoxin detection has yet to be achieved, but in time the inherent advantages of engineered rAb are set to provide the next generation of ultra-high performing binder reagents for the rapid and specific detection of hapten biotoxins.

  20. Progress in the development of immunoanalytical methods incorporating recombinant antibodies to small molecular weight biotoxins.

    Science.gov (United States)

    Kavanagh, Owen; Elliott, Christopher T; Campbell, Katrina

    2015-04-01

    Rapid immunoanalytical screening of food and environmental samples for small molecular weight (hapten) biotoxin contaminations requires the production of antibody reagents that possess the requisite sensitivity and specificity. To date animal-derived polyclonal (pAb) and monoclonal (mAb) antibodies have provided the binding element of the majority of these assays but recombinant antibodies (rAb) isolated from in vitro combinatorial phage display libraries are an exciting alternative due to (1) circumventing the need for experimental animals, (2) speed of production in commonly used in vitro expression systems and (3) subsequent molecular enhancement of binder performance. Short chain variable fragments (scFv) have been the most commonly employed rAb reagents for hapten biotoxin detection over the last two decades but antibody binding fragments (Fab) and single domain antibodies (sdAb) are increasing in popularity due to increased expression efficiency of functional binders and superior resistance to solvents. rAb-based immunochromatographic assays and surface plasmon resonance (SPR) biosensors have been reported to detect sub-regulatory levels of fungal (mycotoxins), marine (phycotoxins) and aquatic biotoxins in a wide range of food and environmental matrices, however this technology has yet to surpass the performances of the equivalent mAb- and pAb-based formats. As such the full potential of rAb technology in hapten biotoxin detection has yet to be achieved, but in time the inherent advantages of engineered rAb are set to provide the next generation of ultra-high performing binder reagents for the rapid and specific detection of hapten biotoxins. PMID:25716465

  1. A PAUF-neutralizing antibody targets both carcinoma and endothelial cells to impede pancreatic tumor progression and metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Su Jin [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); New Drug Development Center, Osong Medical Innovation Foundation, Cheongwon, Chungbuk (Korea, Republic of); Chang, Suhwan [Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Lee, Yangsoon; Kim, Na Young; Hwang, Yeonsil; Min, Hye Jin; Yoo, Kyung-Sook; Park, Eun Hye; Kim, Seokho [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Chung, Young-Hwa [BK21-plus, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan (Korea, Republic of); Park, Young Woo [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Koh, Sang Seok, E-mail: sskoh@dau.ac.kr [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Department of Biological Sciences, Dong-A University, Busan (Korea, Republic of)

    2014-11-07

    Highlights: • PMAb83, a human monoclonal antibody against PAUF, impaired tumor progression in vivo. • PMAb83 attenuated aggressiveness of tumor cells and suppressed angiogenesis. • PMAb83 in combination with gemcitabine conferred improved survival of mouse model. - Abstract: Pancreatic adenocarcinoma up-regulated factor (PAUF) is expressed in pancreatic ductal adenocarcinoma (PDAC) and plays an important role in tumor progression and metastasis. Here we evaluate the anti-tumor efficacy of a human monoclonal antibody against PAUF, PMAb83, to provide a therapeutic intervention to treat the disease. PMAb83 reduced tumor growth and distant metastasis in orthotopically xenografted mice of human PDAC cells. PMAb83 treatment retarded proliferation along with weakened aggressiveness traits of the carcinoma cells. AKT/β-catenin signaling played a role in the carcinoma cell proliferation and the treated xenograft tumors exhibited reduced levels of β-catenin and cyclin D1. Moreover PMAb83 abrogated the PAUF-induced angiogenic responses of endothelial cells, reducing the density of CD31{sup +} vessels in the treated tumors. In combination with gemcitabine, PMAb83 conferred enhanced survival of xenografted mice by about twofold compared to gemcitabine alone. Taken together, our findings show that PMAb83 treatment decreases the aggressiveness of carcinoma cells and suppresses tumor vascularization, which culminates in mitigated tumor growth and metastasis with improved survival in PDAC mouse models.

  2. Final Technical Progress Report Long term risk from actinides in the environment: Modes of mobility; FINAL

    International Nuclear Information System (INIS)

    in diameter and approximately 22 cm long. A thin ''marker layer'' of white soil was added to the top of each column followed by a thin layer of soil that had been spiked with 137Cs, cerium and lanthanum was applied to the surface. Approximately 900 cm of water (the equivalent of about 30 years of rainfall) was then applied at a rate of 3.2 L d-1. All of the activity contained in the soil core appeared to be in the top few mm of soil, i.e. there was virtually no movement of the 134Cs labeled particles. Finally, a library of object-oriented model components was created using Visual Basic to support the construction of contaminant transport models. These components greatly simplify the task of building 1- to 3- dimensional simulation models for risk assessment. The model components created under this funding were subsequently applied to help answer questions regarding risks from irrigation associated with potential releases from the Yucca Mountain waste repository

  3. Oculopharyngeal muscular dystrophy as a cause of progression of weakness in antibody positive myasthenia gravis

    OpenAIRE

    Oskarsson, Björn; Ringel, Steven P.

    2013-01-01

    Many neuromuscular conditions cause bulbar and limb weakness, and when several conditions coexist they present additional diagnostic challenges. Here we describe a case of a 45-year-old woman with antibody positive myasthenia gravis since age 16, who then develops treatment-resistant weakness due to genetically proven oculopharyngeal muscular dystrophy. We conclude that the development of treatment-resistant weakness in myasthenia gravis should spur further work up for other neuromuscular dis...

  4. S100A4-neutralizing antibody suppresses spontaneous tumor progression, pre-metastatic niche formation and alters T-cell polarization balance

    DEFF Research Database (Denmark)

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

    2015-01-01

    the mode of action of 6B12, a S100A4 neutralizing antibody. METHODS: The therapeutic effect of the 6B12 antibody was evaluated in two different mouse models. First, in a model of spontaneous breast cancer we assessed the dynamics of tumor growth and metastasis. Second, in a model of metastatic niche......, decreased vessel density and inhibition of metastases. CONCLUSION: The S100A4 blocking antibody (6B12) reduces tumor growth and metastasis in a model of spontaneous breast cancer. The 6B12 antibody treatment inhibits T cell accumulation at the primary and pre-metastatic tumor sites. The 6B12 antibody acts......BACKGROUND: The tumor microenvironment plays a determinative role in stimulating tumor progression and metastasis. Notably, tumor-stroma signals affect the pattern of infiltrated immune cells and the profile of tumor-released cytokines. Among the known molecules that are engaged in stimulating...

  5. Monoclonal antibodies against antigens displayed on a progressively growing mammary tumor.

    OpenAIRE

    Tax, A; Manson, L A

    1981-01-01

    We have produced lymphocyte hybridomas between mouse myeloma cells and either spleen cells of C3H/f/C57BL/6 mice bearing the Mm5mt/c1 tumor-producing murine mammary tumor virus (MMTV) or spleen cells from Fisher rats inoculated with the same tumor. Two classes of hybridoma-secreted monoclonal antibodies were obtained. In the first class are IVC11, IIIA1, and VE7, each of which precipitated a 52,000-dalton protein from 125I-labeled purified preparations of MMTV and [3H]glucosamine-labeled Mm5m...

  6. Chemoradiotherapy of cancer using boronated monoclonal antibodies. Comprehensive progress report, April 1, 1982-October 31, 1984

    International Nuclear Information System (INIS)

    Research to develop boron neutron capture for radiotherapy applications is summarized. Work is reported in the following areas: (1) chemical and biochemical research with B12H11SH2-; (2) chemical and protein-binding studies with B12H11NCO2- and (CH3)3NB10H8NCO1-; (3) effects of neutron irradiation and capture on phytomitogen stimulated lymphocyte blastogenesis; (4) production and characterization of monoclonal antibodies directed against the murine B16 melanoma; (5) reactor description and determination of flux profile; (6) determination of neutron profile; (7) improvement of the neutron beam by the bismuth scatterer method; and (8) in vitro sensitivity of B16 melanoma cells to thermal neutrons and 10B(n,α) capture. 11 references

  7. Progression of Mycoplasma hyosynoviae infection in three pig herds. Development of tonsillar carrier state, arthritis and antibodies in serum and synovial fluid in pigs from birth to slaughter

    DEFF Research Database (Denmark)

    Hagedorn-Olsen, T.; Nielsen, N.C.; Friis, N.F.;

    1999-01-01

    In this investigation, natural infection with Mycoplasma hyosynoviae was followed in groups of individual pigs in three different herds with regard to occurrence of tonsillar carrier state, clinical arthritis and development of antibodies in serum and in synovial fluid. Antibodies were detected b...... on age, Immunity virulence factors and/or infection pressure; in some herds maybe combined with certain triggering mechanisms such as stress and lowered general resistance.......In this investigation, natural infection with Mycoplasma hyosynoviae was followed in groups of individual pigs in three different herds with regard to occurrence of tonsillar carrier state, clinical arthritis and development of antibodies in serum and in synovial fluid. Antibodies were detected...... by a polyclonal enzyme-linked immunosorbent assay (ELISA) developed for experimental use. The infection with M hyosynoviae progressed very differently in the three herds investigated. In one herd, the infection was apparently limited to adult Figs. In a second herd, all pigs became tonsillar carriers of M...

  8. Flow-induced vibration for light water reactors. Final progress report, July 1981-September 1981

    International Nuclear Information System (INIS)

    Flow-Induced Vibration for Light Water Reactors (FIV for LWRs) is a program designed to improve the FIV performance of light water reactors through the development of design criteria, analytical models for predicting behavior of components, and general scaling laws to improve the accuracy of reduced-scale tests, and through the identification of high FIV risk areas. The program is managed by the General Electric Nuclear Power Systems Engineering Department and has three major contributors: General Electric Nuclear Power Systems Engineering Department (NPSED), General Electric Corporate Research and Development (CR and D) and Argonne National Laboratory (ANL). The program commenced December 1, 1976. This progress report summarizes the accomplishments achieved during the final period from July 1981 to September 1981. This is the last quarterly progress report to be issued for this program

  9. Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies

    DEFF Research Database (Denmark)

    Pörksen, Sven; Laborie, Lene; Nielsen, Lotte;

    2010-01-01

    BACKGROUND:To investigate disease progression the first 12 months after diagnosis in children with type 1 diabetes negative (AAB negative) for pancreatic autoantibodies [islet cell autoantibodies(ICA), glutamic acid decarboxylase antibodies (GADA) and insulinoma-associated antigen-2 antibodies (IA......-2A)]. Furthermore the study aimed at determining whether mutations in KCNJ11, ABCC8, HNF1A, HNF4A or INS are common in AAB negative diabetes.MATERIALS AND METHODS:In 261 newly diagnosed children with type 1 diabetes, we measured residual î-cell function, ICA, GADA, and IA-2A at 1, 6 and 12 months...... treatment after four weeks on 1.0-1.2 mg/kg/24 h glibenclamide.CONCLUSION:GAD, IA-2A, and ICA negative children with new onset type 1 diabetes have slower disease progression as assessed by residual beta-cell function and improved glycemic control 12 months after diagnosis. One out of 24 had a mutation...

  10. Single chain FV constructs of anti-ganglioside GD2 antibodies for radioimaging and radioimmumotheraphy. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Cheung, N.K.V.; Larson, S.M.

    1993-11-01

    For the past several years, we have studied the anti-G{sub D2} murine monoclonal antibody, 3F8, in radiolabeled form, for diagnosis and therapy of neuroblastoma. The targeting properties of this antibody/antigen system are exceptional, with uptakes consistently in the highest range of reported results for in vivo human studies. The radioiodinated antibody 3F8 is now used by us as our criteria for diagnosis and staging of advanced neuroblastoma. This antibody is showing considerable promise also in our Phase I trials in Stage 4 neuroblastoma, and major responses are being seen at current dose level, with manageable marrow toxicity, but no limiting organ toxicity.

  11. Rates and determinants of progression to graft failure in kidney allograft recipients with de novo donor-specific antibody.

    Science.gov (United States)

    Wiebe, C; Gibson, I W; Blydt-Hansen, T D; Pochinco, D; Birk, P E; Ho, J; Karpinski, M; Goldberg, A; Storsley, L; Rush, D N; Nickerson, P W

    2015-11-01

    Understanding rates and determinants of clinical pathologic progression for recipients with de novo donor-specific antibody (dnDSA), especially subclinical dnDSA, may identify surrogate endpoints and inform clinical trial design. A consecutive cohort of 508 renal transplant recipients (n = 64 with dnDSA) was studied. Recipients (n = 388) without dnDSA or dysfunction had an eGFR decline of -0.65 mL/min/1.73 m(2) /year. In recipients with dnDSA, the rate eGFR decline was significantly increased prior to dnDSA onset (-2.89 vs. -0.65 mL/min/1.73 m(2) /year, p < 0.0001) and accelerated post-dnDSA (-3.63 vs. -2.89 mL/min/1.73 m(2) /year, p < 0.0001), suggesting that dnDSA is both a marker and contributor to ongoing alloimmunity. Time to 50% post-dnDSA graft loss was longer in recipients with subclinical versus a clinical dnDSA phenotype (8.3 vs. 3.3 years, p < 0.0001). Analysis of 1091 allograft biopsies found that dnDSA and time independently predicted chronic glomerulopathy (cg), but not interstitial fibrosis and tubular atrophy (IFTA). Early T cell-mediated rejection, nonadherence, and time were multivariate predictors of IFTA. Independent risk factors for post-dnDSA graft survival available prior to, or at the time of, dnDSA detection were delayed graft function, nonadherence, dnDSA mean fluorescence intensity sum score, tubulitis, and cg. Ultimately, dnDSA is part of a continuum of mixed alloimmune-mediated injury, which requires solutions targeting T and B cells.

  12. Final Technical Progress Report: Development of Low-Cost Suspension Heliostat; December 7, 2011 - December 6, 2012

    Energy Technology Data Exchange (ETDEWEB)

    Bender, W.

    2013-01-01

    Final technical progress report of SunShot Incubator Solaflect Energy. The project succeeded in demonstrating that the Solaflect Suspension Heliostat design is viable for large-scale CSP installations. Canting accuracy is acceptable and is continually improving as Solaflect improves its understanding of this design. Cost reduction initiatives were successful, and there are still many opportunities for further development and further cost reduction.

  13. Improved methods for water shutoff. Final technical progress report, October 1, 1997--September 30, 1998

    Energy Technology Data Exchange (ETDEWEB)

    Seright, R.S.; Liang, J.T.; Schrader, R.; Hagstrom, J. II; Liu, J.; Wavrik, K.

    1998-10-01

    In the United States, more than 20 billion barrels of salt water are produced each year during oilfield operations. A tremendous economic incentive exists to reduce water production if that can be accomplished without significantly sacrificing hydrocarbon production. This three-year research project had three objectives. The first objective was to identify chemical blocking agents that will (a) during placement, flow readily through fractures without penetrating significantly into porous rock and with screening out or developing excessive pressure gradients and (b) at a predictable and controllable time, become immobile and resistant breakdown upon exposure to moderate to high pressure gradients. The second objective was to identify schemes that optimize placement of the above blocking agents. The third objective was to explain why gels and other chemical blocking agents reduce permeability to one phase (e.g., water) more than that to another phase (e.g., oil or gas). The authors also wanted to identify conditions that maximize this phenomenon. This project consisted of three tasks, each of which addressed one of the above objectives. This report describes work performed during the third and final period of the project. During this three-year project, they: (1) Developed a procedure and software for sizing gelant treatments in hydraulically fractured production wells; (2) Developed a method (based on interwell tracer results) to determine the potential for applying gel treatments in naturally fractured reservoirs; (3) Characterized gel properties during extrusion through fractures; (4) Developed a method to predict gel placement in naturally fractured reservoirs; (5) Made progress in elucidating the mechanism for why some gels can reduce permeability to water more than that to oil; (6) Demonstrated the limitations of using water/oil ratio diagnostic plots to distinguish between channeling and coning; and (7) Proposed a philosophy for diagnosing and attacking water

  14. High-Efficiency Nitride-Based Solid-State Lighting. Final Technical Progress Report

    International Nuclear Information System (INIS)

    In this final technical progress report we summarize research accomplished during Department of Energy contract DE-FC26-01NT41203, entitled ''High-Efficiency Nitride-Based Solid-State Lighting''. Two teams, from the University of California at Santa Barbara (Principle Investigator: Dr. Shuji Nakamura) and the Lighting Research Center at Rensselaer Polytechnic Institute (led by Dr. N. Narendran), pursued the goals of this contract from thin film growth, characterization, and packaging/luminaire design standpoints. The UCSB team initially pursued the development of blue gallium nitride (GaN)-based vertical-cavity surface-emitting lasers, as well as ultraviolet GaN-based light emitting diodes (LEDs). In Year 2, the emphasis shifted to resonant-cavity light emitting diodes, also known as micro-cavity LEDs when extremely thin device cavities are fabricated. These devices have very directional emission and higher light extraction efficiency than conventional LEDs. Via the optimization of thin-film growth and refinement of device processing, we decreased the total cavity thickness to less than 1 (micro)m, such that micro-cavity effects were clearly observed and a light extraction efficiency of over 10% was reached. We also began the development of photonic crystals for increased light extraction, in particular for so-called ''guided modes'' which would otherwise propagate laterally in the device and be re-absorbed. Finally, we pursued the growth of smooth, high-quality nonpolar a-plane and m-plane GaN films, as well as blue light emitting diodes on these novel films. Initial nonpolar LEDs showed the expected behavior of negligible peak wavelength shift with increasing drive current. M-plane LEDs in particular show promise, as unpackaged devices had unsaturated optical output power of ∼ 3 mW at 200 mA drive current. The LRC's tasks were aimed at developing the subcomponents necessary for packaging UCSB's light emitting diodes, and packaging them to produce a white light

  15. Progression to type 1 diabetes in islet cell antibody-positive relatives in the European Nicotinamide Diabetes Intervention Trial

    DEFF Research Database (Denmark)

    Bingley, P J; Gale, E A M; Reimers, Jesper Irving

    2006-01-01

    AIMS/HYPOTHESIS: To examine the role of additional immune, genetic and metabolic risk markers in determining risk of diabetes in islet cell antibody (ICA)-positive individuals with a family history of type 1 diabetes recruited into the European Nicotinamide Diabetes Intervention Trial. METHODS...

  16. Study of private enterprise development on the Raft River KGRA. Final progress report

    Energy Technology Data Exchange (ETDEWEB)

    Green, S.J.; Brown, W.S.; Meldrum, P.D.

    1977-07-01

    Information, analysis, and conclusions based on the small for-profit venture business model are presented. The necessary tasks are described and progress is reviewed. Water availability and business analysis problems are described. Included in the appendix are materials on land availability, characterization of geothermal resources under Idaho law, and greenhouse analysis and geothermal applications. (MHR)

  17. Progression of Mycoplasma hyosynoviae infection in three pig herds. Development of tonsillar carrier state, arthritis and antibodies in serum and synovial fluid in pigs from birth to slaughter.

    Science.gov (United States)

    Hagedorn-Olsen, T; Nielsen, N C; Friis, N F; Nielsen, J

    1999-11-01

    In this investigation, natural infection with Mycoplasma hyosynoviae was followed in groups of individual pigs in three different herds with regard to occurrence of tonsillar carrier state, clinical arthritis and development of antibodies in serum and in synovial fluid. Antibodies were detected by a polyclonal enzyme-linked immunosorbent assay (ELISA) developed for experimental use. The infection with M. hyosynoviae progressed very differently in the three herds investigated. In one herd, the infection was apparently limited to adult pigs. In a second herd, all pigs became tonsillar carriers of M. hyosynoviae, but no mycoplasma-related arthritis nor any serological response was demonstrated within the growing-finishing period. In the third herd investigated, tonsillar infection was detected in all pigs, clinical cases of M. hyosynoviae arthritis followed and a moderate serological response was observed in some, but not all, pigs. In all three herds, M. hyosynoviae infection was carried in the tonsils of the adult pigs, but it was only occasionally transmitted from sows to piglets. Maternal antibodies were transferred to the piglets and persisted for approximately 8-12 weeks. After weaning, some pigs became infected before 20 weeks of age, while others did not. In the majority of cases, the tonsillar infection was established from 11 weeks of age or older. A latent tonsillar infection was present for a period of several weeks within the group of investigated pigs before cases of generalized infection and arthritis were seen. In some cases, generalization of M. hyosynoviae infection in the blood and in joints was observed in spite of the detection of an active serological response a few weeks earlier. The present work suggests that generalization of the infection and development of arthritis may depend on age, immunity, virulence factors and/or infection pressure; in some herds maybe combined with certain triggering mechanisms such as stress and lowered general

  18. Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies

    DEFF Research Database (Denmark)

    Pörksen, Sven; Laborie, Lene; Nielsen, Lotte;

    2010-01-01

    BACKGROUND:To investigate disease progression the first 12 months after diagnosis in children with type 1 diabetes negative (AAB negative) for pancreatic autoantibodies [islet cell autoantibodies(ICA), glutamic acid decarboxylase antibodies (GADA) and insulinoma-associated antigen-2 antibodies (IA......-2A)]. Furthermore the study aimed at determining whether mutations in KCNJ11, ABCC8, HNF1A, HNF4A or INS are common in AAB negative diabetes.MATERIALS AND METHODS:In 261 newly diagnosed children with type 1 diabetes, we measured residual î-cell function, ICA, GADA, and IA-2A at 1, 6 and 12 months....... Patients, who were AAB-negative throughout the 12-month period, had higher residual î-cell function (P = 0.002), lower blood glucose (P = 0.004), received less insulin (P = 0.05) and had lower HbA1c (P = 0.02) 12 months after diagnosis. One patient had a heterozygous mutation leading to the substitution...

  19. Processes of energy deposition by heavy-particle and electron impact. Final progress report

    International Nuclear Information System (INIS)

    Progress is reported in three areas of reasearch during the present period: K-shell ionization in high energy collisions of heavy ions with light target atoms using the sudden (Magnus) approximation, K-L level matching phenomena associated with K-shell vacancy production in heavy-ion collisions, and studies of low energy collisions of electrons with molecules using semi-classical perturbation theory. A brief discussion of each of these activities is given

  20. Biomedical Computing Technology Information Center (BCTIC): Final progress report, March 1, 1986-September 30, 1986

    International Nuclear Information System (INIS)

    During this time, BCTIC packaged and disseminated computing technology and honored all requests made before September 1, 1986. The final month of operation was devoted to completing code requests, returning submitted codes, and sending out notices of BCTIC's termination of services on September 30th. Final BCTIC library listings were distributed to members of the active mailing list. Also included in the library listing are names and addresses of program authors and contributors in order that users may have continued support of their programs. The BCTIC library list is attached

  1. Clonal progression during the T cell-dependent B cell antibody response depends on the immunoglobulin DH gene segment repertoire.

    Directory of Open Access Journals (Sweden)

    Ahmad eTrad

    2014-08-01

    Full Text Available The diversity of the third complementarity determining region of the Ig H chain is constrained by natural selection of immunoglobulin diversity (DH sequence. To test the functional significance of this constraint in the context of thymus-dependent (TD immune responses, we immunized BALB/c mice with WT or altered DH sequence with 2-phenyloxazolone-coupled chicken serum albumin (phOx-CSA. We chose this antigen because studies of the humoral immune response to the hapten phOx were instrumental in the development of the current theoretical framework on which our understanding of the forces driving TD responses is based. To allow direct comparison, we used the classic approach of generating monoclonal Ab (mAb from various stages of the immune response to phOx to assess the effect of changing the sequence of the DH on clonal expansion, class switching and affinity maturation, which are hallmarks of TD responses. Compared to WT, TD-induced humoral IgM as well as IgG antibody production in the D-altered D-DFS and D-iD strains were significantly reduced. An increased prevalence of IgM producing hybridomas from late primary, secondary, and tertiary memory responses suggested either impaired class switch recombination (CSR or impaired clonal expansion of class switched B cells with phOx reactivity. Neither of the D-altered strains demonstrated the restriction in the VH/VL repertoire, the elimination of VH1 family-encoded antibodies, the focusing of the distribution of CDR-H3 lengths, or the selection for the normally dominant Ox1 clonotype which all are hallmarks of the anti-phOx response in WT mice. These changes in clonal selection and expansion as well as class switch recombination indicate that the genetic constitution of the DH locus, which has been selected by evolution, can strongly influence the functional outcome of a TD humoral response.

  2. Detection of serum antibodies to ovine progressive pneumonia virus in sheep by using a caprine arthritis-encephalitis virus competitive-inhibition enzyme-linked immunosorbent assay.

    Science.gov (United States)

    Herrmann, Lynn M; Cheevers, William P; Marshall, Katherine L; McGuire, Travis C; Hutton, Melinda M; Lewis, Gregory S; Knowles, Donald P

    2003-09-01

    A competitive-inhibition enzyme-linked immunosorbent assay (cELISA) for detection of antibodies to the surface envelope (SU) of caprine arthritis-encephalitis virus (CAEV) was recently reported (L. M. Herrmann, W. P. Cheevers, T. C. McGuire, D. Scott Adams, M. M. Hutton, W. G. Gavin, and D. P. Knowles, Clin. Diagn. Lab. Immunol. 10:267-271, 2003). The cELISA utilizes CAEV-63 SU captured on microtiter plates using the monoclonal antibody (MAb) F7-299 and measures competitive displacement of binding of the anti-CAEV MAb GPB 74A by goat serum. The present study evaluated the CAEV cELISA for detection of antibodies to ovine progressive pneumonia virus (OPPV) in sheep. Three hundred thirty-two sera were randomly selected from 21,373 sheep sera collected throughout the United States to determine the sensitivity and specificity of cELISA and agar gel immunodiffusion (AGID) based on immunoprecipitation (IP) of [35S]methionine-labeled OPPV antigens as a standard of comparison. A positive cELISA test was defined as >20.9 percent inhibition (% I) of MAb 74A binding based on two standard deviations above the mean % I of 191 IP-negative sheep sera. At this cutoff, there were 2 of 141 false-negative sera (98.6% sensitivity) and 6 of 191 false-positive sera (96.9% specificity). Sensitivity and specificity values for IP-monitored AGID were comparable to those for cELISA for 314 of 332 sera with unambiguous AGID results. Concordant results by cELISA and IP resolved 16 of the 18 sera that were indeterminate by AGID. Additional studies evaluated cELISA by using 539 sera from a single OPPV-positive flock. Based on IP of 36 of these sera, there was one false-negative by cELISA among 21 IP-positive sera (95.5% sensitivity) and 0 of 15 false-positives (100% specificity). We conclude that the CAEV cELISA can be applied to detection of OPPV antibodies in sheep with high sensitivity and specificity. PMID:12965917

  3. MHC class I chain-related protein A antibodies and shedding are associated with the progression of multiple myeloma

    OpenAIRE

    Jinushi, Masahisa; Vanneman, Matthew; Munshi, Nikhil C.; Tai, Yu-Tzu; Prabhala, Rao H.; Ritz, Jerome; Neuberg, Donna; Anderson, Kenneth C; Carrasco, Daniel Ruben; Dranoff, Glenn

    2008-01-01

    Monoclonal gammopathy of undetermined significance (MGUS) is a common disorder of aging and a precursor lesion to full-blown multiple myeloma (MM). The mechanisms underlying the progression from MGUS to MM are incompletely understood but include the suppression of innate and adaptive antitumor immunity. Here, we demonstrate that NKG2D, an activating receptor on natural killer (NK) cells, CD8+ T lymphocytes, and MHC class I chain-related protein A (MICA), an NKG2D ligand induced in malignant p...

  4. Final Report on Models, Periodic Progress, Report No D1.3, Globeman21, ESPRIT 26509

    DEFF Research Database (Denmark)

    Pedersen, Jens Dahl; Tølle, Martin; Vesterager, Johan

    1999-01-01

    This deliverable D1.3 is the third and final deliverable of WP1 - Global Manufacturing Concept of the European part of the Globeman21 project. The report essentially presents the final models on generic Extended Enterprise Management (EEM) and generic Product Life Cycle Management (PLCM......), a collection of practical experiences, and requirements for enhanced methods and tools for modelling. First, the deliverable outlines the GM21 understanding regarding extended enterprises and virtual enterprises. This is done by extracting and synthesising the essence of key definitions and concepts...... Framework forms the common structure for the work and results of this deliverable. The deliverable furthermore discusses work preparation as an important activity in extended enterprise planning. In this relation different forms of work preparation are introduced and discussed leading to a specific...

  5. Experimental Program Final Technical Progress Report: 15 February 2007 to 30 September 2012

    Energy Technology Data Exchange (ETDEWEB)

    Kinney, Edward R. [University of Colorado, Boulder, CO

    2014-09-12

    This is the final technical report of the grant DE-FG02-04ER41301 to the University of Colorado at Boulder entitled "Intermediate Energy Nuclear Physics" and describes the results of our funded activities during the period 15 February 2007 to 30 September 2012. These activities were primarily carried out at Fermilab, RHIC, and the German lab DESY. Significant advances in these experiments were carried out by members of the Colorado group and are described in detail.

  6. Thyroid Antibodies

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? Thyroid Antibodies Share this page: Was this page helpful? Also known as: Thyroid Autoantibodies; Antithyroid Antibodies; Antimicrosomal Antibody; Thyroid Microsomal Antibody; ...

  7. Generation and characterization of a tetraspanin CD151/integrin α6β1-binding domain competitively binding monoclonal antibody for inhibition of tumor progression in HCC

    Science.gov (United States)

    Cai, Jia-Bin; Huang, Xiao-Yong; Wu, Chao; Zhang, Lu; Kang, Qiang; Liu, Li-Xin; Xie, Nan; Shen, Zao-Zhuo; Hu, Mei-Yu; Cao, Ya; Qiu, Shuang-Jian; Sun, Hui-Chuan; Zhou, Jian; Fan, Jia; Shi, Guo-Ming

    2016-01-01

    Our previous studies revealed that tetraspanin CD151 plays multiple roles in the progression of hepatocellular carcinoma (HCC) by forming a functional complex with integrin α6β1. Herein, we generated a monoclonal antibody (mAb) that dissociates the CD151/integrin α6β1 complex, and we evaluated its bioactivity in HCCs. A murine mAb, tetraspanin CD151 (IgG1, called CD151 mAb 9B), was successfully generated against the CD151-integrin α6β1 binding site of CD151 extracellular domains. Co-immunoprecipitation using CD151 mAb 9B followed by Western blotting detected a 28 kDa protein. Both immunofluorescent and immunohistochemical staining showed a good reactivity of CD151 mAb 9B in the plasma membrane and cytoplasm of HCC cells, as well as in liver cells. In vitro assays demonstrated that CD151 mAb 9B could inhibit neoangiogenesis and both the mobility and the invasiveness of HCC cells. An in vivo assay showed that CD151 mAb 9B inhibited tumor growth potential and HCC cells metastasis. We successfully produced a CD151 mAb 9B targeting the CD151/integrin α6β1-binding domain, which not only can displayed good reactivity to the CD151 antigen but also prevented tumor progression in HCC. PMID:26756217

  8. Preventing the infiltration of leukocytes by monoclonal antibody blocks the development of progressive ischemia in rat burns.

    Science.gov (United States)

    Choi, M; Rabb, H; Arnaout, M A; Ehrlich, H P

    1995-10-01

    Tissue loss as a consequence of thermal trauma occurs in two stages. There is immediate necrosis in tissues directly killed by the thermal energy, followed by a delayed secondary necrosis in neighboring tissues. The infiltration of neutrophils into traumatized tissues is a hallmark of the inflammatory response. Neutrophils have the machinery to kill invading microorganisms, but these same weapons have the capacity to destroy the host's viable tissues as well. Leukocyte infiltration requires their adherence to the vascular endothelial cell surface. Masking these adhesion sites on neutrophils will block the adhesion of neutrophils to the endothelium. A monoclonal antibody (mAb) was developed to guinea pig leukocyte adhesion sites CD11b/ CD18, and this mAb cross-reacts with rat leukocytes, blocking their adherence. Rats received a "comb burn" composed of four rectangular full-thickness burns placed in a row and separated by three areas left unburned. The four individual burns convert into a single large wound because the blood flow to the interspaces was terminated, blood vessels were occluded, and leukocytes were present in the extravascular space. The systemic administration of the mAb (50 to 150 microliters) immediately following a comb burn promoted the survival of the interspace, demonstrated by the prevention of loss of blood flow by laser Doppler monitoring, maintained patent vessels by latex vascular casts, blocked extravascular migration of neutrophils histologically at 2 hours, and limited the tissue loss to the original four burns. PMID:7568496

  9. [Tampa Electric Company IGCC project]. Final public design report; Technical progress report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-07-01

    This final Public Design Report (PDR) provides completed design information about Tampa Electric Company`s Polk Power Station Unit No. 1, which will demonstrate in a commercial 250 MW unit the operating parameters and benefits of the integration of oxygen-blown, entrained-flow coal gasification with advanced combined cycle technology. Pending development of technically and commercially viable sorbent for the Hot Gas Cleanup System, the HGCU also is demonstrated. The report is organized under the following sections: design basis description; plant descriptions; plant systems; project costs and schedule; heat and material balances; general arrangement drawings; equipment list; and miscellaneous drawings.

  10. Biologic considerations in anatomic imaging with radionuclides. Final progress report, July 1974--June 1975

    International Nuclear Information System (INIS)

    An important task relating to anatomic imaging with radionuclides is the determination of factors which effect the use of imaging procedures. This is important to reduce radiation exposure in the population, to improve the efficacy of diagnostic imaging procedures and finally to provide a basis for evaluating the potential effects of proposed regulation of use rates. In this report we describe a methodology for obtaining clinical data relating to the use of the brain scan in an inner city teaching hospital. The development of a questionnaire suitable for use in a clinical setting and providing both prospective and retrospective data is presented. The results of the use of the questionnaire at the Johns Hopkins Hospital during a three month period in 1974 are shown and discussed. Some preliminary results from these data are given and a method for further analysis is indicated

  11. Advanced Coal Conversion Process Demonstration Project. Final technical progress report, January 1, 1995--December 31, 1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-05-01

    This report describes the technical progress made on the Advanced Coal Conversion Process (ACCP) Demonstration Project from January 1, 1995 through December 31, 1995. This project demonstrates an advanced, thermal, coal upgrading process, coupled with physical cleaning techniques, that is designed to upgrade high-moisture, low-rank coals to a high-quality, low-sulfur fuel, registered as the SynCoal Process. The coal is processed through three stages (two heating stages followed by an inert cooling stage) of vibrating fluidized bed reactors that remove chemically bound water, carboxyl groups, and volatile sulfur compounds. After thermal upgrading, the coal is put through a deep-bed stratifier cleaning process to separate the pyrite-rich ash from the coal. The SynCoal Process enhances low-rank, western coals, usually with a moisture content of 25 to 55 percent, sulfur content of 0.5 to 1.5 percent, and heating value of 5,5000 to 9,000 British thermal units per pound (Btu/lb), by producing a stable, upgraded, coal product with a moisture content as low as 1 percent, sulfur content as low as 0.3 percent, and heating value up to 12,000 Btu/lb. During this reporting period, the primary focus for the ACCP Demonstration Project team was to expand SynCoal market awareness and acceptability for both the products and the technology. The ACCP Project team continued to focus on improving the operation, developing commercial markets, and improving the SynCoal products as well as the product`s acceptance.

  12. Theoretical studies in nuclear structure. Final progress report, June 1, 1991--July 31, 1996

    Energy Technology Data Exchange (ETDEWEB)

    Marshalek, E.R.

    1997-06-01

    The general purview of the project is the theory of collective motion in atomic nuclei. The chief aim is to elucidate the phenomena of (1) anharmonic multiphonon excitations, and (2) collective tilted rotation, both of which are topics of considerable current interest. In the primary stage of an investigation it is often necessary to develop appropriate mathematical tools, as was the case here. In the next stage, the formalism must be tested on simple soluble models. The work described here is mainly concerned with these two stages. The final stage of realistic applications will require more time, manpower and, of course, the necessary funding. Some planning for this last stage has been carried out and anticipated problems axe briefly discussed. As it turns out, both of the above topics can be approached within the unified framework of a theorem that I developed, called the Cranking Bifurcation Theorem (CBT) to be described below. The CBT can be regarded as an outgrowth of the boson expansion method, which provides a general, and, in principal, exact formalism for treating collective excitations. We begin with a brief discussion of the CBT and then continue on to the applications.

  13. Light scattering studies of lower dimensional colloidal particle and critical fluid systems. Final progress report

    International Nuclear Information System (INIS)

    We have completed a program of small angle scattering Rayleigh linewidth measurements on thin films of a 2,6-lutidine + water mixture. No statistically significant departures from three dimensional dynamic response were seen, although the conditions set by the theory of Calvo and Ferrell were met. We have applied digital image processing to evaluate fractal scale invariance in two dimensional particle aggregates arising from the induced coagulation of colloidal particle monolayer crystals. Our system gives us the capability of calculating the pair correlation function for both small and very large (2 x 104 particles) particle clusters. We find evidence of an apparent crossover between kinetic clustering aggregation at small distances (about 20 particle diameters) to percolation or gel/sol transition-behavior at large distances. This is evident in both isolated clusters and in final state ''giant'' aggregates. We are carrying through a parallel program of computer calculations whose motivation is to assess the sensitivity of experimental measures of self similarity to cluster size and image resolution, and to generate efficient algorithms which can be applied to calculate fractal ''critical exponents'' other than the Hausdorff dimension. We have succeeded in measuring the surface tension of a water surface covered by a colloidal particle monolayer crystal, in both its repulsive-dipole and close-packed van der Waals phases

  14. Novel catalysts for methane activation. Final progress report, September 30, 1992--April 30, 1996

    Energy Technology Data Exchange (ETDEWEB)

    Hirschon, A.S.; Du, Y.; Wu, H.J.; Malhotra, R.; Wilson, R.B.

    1996-06-11

    This final report summarizes the results of our research under Contract No. DE-AC22-92PC92112, Novel Catalysts for Methane Activation. In this research we prepared and tested fullerene soots for converting methane into higher hydrocarbons. We conducted the methane conversions using dehydrocoupling conditions, primarily in the temperature regimes of 600{degrees}-1000{degrees}C and atmospheric pressures. The research was divided into three sections. The first section focused on comparing fullerene soots with other forms of carbon such as acetylene black and Norit-A. We found that the fullerene soot was indeed more reactive than the other forms of carbon. However, due to its high reactivity, it was not selective. The second section focused on the effect of metals on the reactivity of the soots, including both transition metals and alkali metals. We found that potassium could enhance the selectivities of fullerene soot to higher hydrocarbons, but the effect was unique to fullerene soot and did not improve the performance of other forms of carbon. The third part focused on the use of co-feeds for methane activation to enhance the selectivities and lower the temperature threshold of methane activation.

  15. Coal plasticity at high heating rates and temperatures. Final technical progress report

    Energy Technology Data Exchange (ETDEWEB)

    Gerjarusak, S.; Peters, W.A.; Howard, J.B.

    1995-05-01

    Plastic coals are important feedstocks in coke manufacture, coal liquefaction, gasification, and combustion. During these processes, the thermoplastic behavior of these coals is also important since it may contribute to desirable or undesirable characteristics. For example, during liquefaction, the plastic behavior is desired since it leads to liquid-liquid reactions which are faster than solid-liquid reactions. During gasification, the elastic behavior is undesired since it leads to caking and agglomeration of coal particles which result in bed bogging in fixed or fluidized bed gasifiers. The plastic behavior of different coals was studied using a fast-response plastometer. A modified plastometer was used to measure the torque required to turn at constant angular speed a cone-shaped disk embedded in a thin layer of coal. The coal particles were packed between two metal plates which are heated electrically. Heating rates, final temperatures, pressures, and durations of experiment ranged from 200--800 K/s, 700--1300 K, vacuum-50 atm helium, and 0--40 s, respectively. The apparent viscosity of the molten coal was calculated from the measured torque using the governing equation of the cone-and-plate viscometer. Using a concentrated suspension model, the molten coal`s apparent viscosity was related to the quantity of the liquid metaplast present during pyrolysis. Seven coals from Argonne National Laboratory Premium Coal Sample Bank were studied. Five bituminous coals, from high-volatile to low-volatile bituminous, were found to have very good plastic behavior. Coal type strongly affects the magnitude and duration of plasticity. Hvb coals were most plastic. Mvb and lvb coals, though the maximum plasticity and plastic period were less. Low rank coals such as subbituminous and lignite did not exhibit any plasticity in the present studies. Coal plasticity is moderately well correlated with simple indices of coal type such as the elemental C,O, and H contents.

  16. Final Progress Report for the NASA Inductrack Model Rocket Launcher at the Lawrence Livermore National Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Tung, L S; Post, R F; Martinez-Frias, J

    2001-06-27

    The Inductrack magnetic levitation system, developed at the Lawrence Livermore National Laboratory, was studied for its possible use for launching rockets. Under NASA sponsorship, a small model system was constructed at the Laboratory to pursue key technical aspects of this proposed application. The Inductrack is a passive magnetic levitation system employing special arrays of high-field permanent magnets (Halbach arrays) on the levitating cradle, moving above a ''track'' consisting of a close-packed array of shorted coils with which are interleaved with special drive coils. Halbach arrays produce a strong spatially periodic magnetic field on the front surface of the arrays, while canceling the field on their back surface. Relative motion between the Halbach arrays and the track coils induces currents in those coils. These currents levitate the cradle by interacting with the horizontal component of the magnetic field. Pulsed currents in the drive coils, synchronized with the motion of the carrier, interact with the vertical component of the magnetic field to provide acceleration forces. Motional stability, including resistance to both vertical and lateral aerodynamic forces, is provided by having Halbach arrays that interact with both the upper and the lower sides of the track coils. At present, a 7.8 meter track composed of drive and levitation coils has been built and the electronic drive circuitry performs as designed. A 9 kg cradle that carries the Halbach array of permanent magnets has been built. A mechanical launcher is nearly complete which will provide an initial cradle velocity of 9 m/s into the electronic drive section. We have found that the drag forces from the levitation coils were higher than in our original design. However, measurements of drag force at velocities less than 1 m/s are exactly as predicted by theory. Provided here are recommended design changes to improve the track's performance so that a final velocity of 40

  17. Final Technical Progress Report Long term risk from actinides in the environment: Modes of mobility

    International Nuclear Information System (INIS)

    in diameter and approximately 22 cm long. A thin ''marker layer'' of white soil was added to the top of each column followed by a thin layer of soil that had been spiked with 137Cs, cerium and lanthanum was applied to the surface. Approximately 900 cm of water (the equivalent of about 30 years of rainfall) was then applied at a rate of 3.2 L d-1. All of the activity contained in the soil core appeared to be in the top few mm of soil, i.e. there was virtually no movement of the 134Cs labeled particles. Finally, a library of object-oriented model components was created using Visual Basic to support the construction of contaminant transport models. These components greatly simplify the task of building 1- to 3- dimensional simulation models for risk assessment. The model components created under this funding were subsequently applied to help answer questions regarding risks from irrigation associated with potential releases from the Yucca Mountain waste repository

  18. Final Technical Progress Report Long term risk from actinides in the environment: Modes of mobility

    Energy Technology Data Exchange (ETDEWEB)

    Thomas B. Kirchner

    2002-03-22

    in diameter and approximately 22 cm long. A thin ''marker layer'' of white soil was added to the top of each column followed by a thin layer of soil that had been spiked with 137Cs, cerium and lanthanum was applied to the surface. Approximately 900 cm of water (the equivalent of about 30 years of rainfall) was then applied at a rate of 3.2 L d-1. All of the activity contained in the soil core appeared to be in the top few mm of soil, i.e. there was virtually no movement of the 134Cs labeled particles. Finally, a library of object-oriented model components was created using Visual Basic to support the construction of contaminant transport models. These components greatly simplify the task of building 1- to 3- dimensional simulation models for risk assessment. The model components created under this funding were subsequently applied to help answer questions regarding risks from irrigation associated with potential releases from the Yucca Mountain waste repository.

  19. Neutralizing antibodies in hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  20. Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Bernstein, Herbert J

    2012-02-06

    The BIOMOL grant was for 'Local System Support for PDB Biological Unit Search and Display' to augment Rasmol's [Bernstein 2000] [Sayle, Milner-White 1995] existing macromolecular display functions with new capabilities by taking advantage of recent increases in local computing power in order to move functionality that is now scattered among various local and remote systems into one local package. Work included new algorithms for molecular surface display, an extended format for Protein Data Bank Entries, work on issues relating to the integration of multiple diffraction images formats.

  1. Final Technical Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    J.Y. Hwang; R.C. Greenlund

    2002-12-31

    Michigan Technological University has demonstrated major inroads in establishing the viability of utilizing aluminum smelting by-product waste materials in lightweight concrete product applications. The research identified key elements of producing various forms of lightweight concrete products through utilizing various procedures and mixture components with the by-product materials. A process was developed through pilot plant testing that results in additional aluminum recovery at finer sizes, a clean returnable salt product through spray drying technology, and a low-salt-content oxide product with enough aluminum metal content that it can be used to form lightweight cementitious mixtures. Having three distinct products aids in generating favorable process economics. Revenue projections from aluminum recovery and salt recovery are enough to cover processing costs and create a cost-free oxide product to market for lightweight concrete applications. This supply side commercialization strategy offers aluminum by-product recyclers a potentially no cost product, which has been demonstrated through this project to create desirable and marketable lightweight concrete products of various forms. Environmental benefits to the public are tremendous. At best, all dross and salt cake materials have the potential to be completely recycled and utilized. At worst, disposal sites would see a reduced amount of material: a post processed oxide product with little salt and no hydrogen sulfide or ammonia gas generating capability, which, if isolated from high alkali conditions, would pose no reactivity concerns. The US aluminum industry has historically, along with the steel industry, been a leader in recycling metal. The findings from this project, increased metal recovery, improved salt recycling, and demonstrated end uses for oxide residues, will go a long way in helping the aluminum industry obtain 100% material utilization and zero discharge.

  2. Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Kotov, Valeri [Univ. of Vermont, Burlington, VT (United States)

    2016-05-29

    The research in this program involves theoretical investigations of electronic, optical and mechanical properties of graphene and its derivatives, such as bi-layer graphene, graphene-based van der Waals heterostructures, strained graphene, as well as graphene on various surfaces. One line of research has been development of theoretical models that support graphene’s large array of possible technological applications. For example one of our goals has been the understanding of surface plasmons and spin relaxation mechanisms in graphene, related to novel optoelectronics and spintronics applications. Our current research focus is on understanding the role of correlations in graphene under mechanical deformations, such as strain. The main goal is to describe the mutual interplay between strain and electron-electron interactions which could lead to the formation of novel elec- tronic phases with strongly modified electronic, magnetic and optical properties. This direction of research contributes to deeper understanding of interactions in graphene and related atomically-thin materials - a subject at the forefront of research on graphene and its derivatives.

  3. Central receiver solar thermal power system, Phase 1. Quarterly progress report (final) for period ending March 31, 1976

    Energy Technology Data Exchange (ETDEWEB)

    None

    1976-10-01

    During this period (January 1976 through March 1976), the primary program effort was expended toward the completion of the detail design of the three major research experiments. Also, the Preliminary Pilot Plant Economic Cost Study was completed. In the Collector Subsystem, the designs for both the twenty-five mirror and the nine-mirror heliostats were completed and released. In the Receiver Subsystem, Foster Wheeler continued with the detail design of the 5 MW research experiment receiver. A preliminary draft of the detailed test plan for the receiver subsystem research experiment was prepared and is now undergoing a final review. The detailed design of the Thermal Storage Subsystem continued at Georgia Institute of Technology. Several incremental detail design reviews were held as the design progressed. During this period, Bechtel completed the preliminary environmental analysis for the Pilot Plant. The optimization studies of the electrical power generation subsystem were initiated. A major effort was the preparation of the preliminary cost analysis for the 10 MWe Central Receiver Solar Thermal Pilot Plant. This task required the development of a cost accounting structure and a definition of all of the costs associated with the design, construction, checkout, and two-year test of the Pilot Plant. (WDM)

  4. Big data:the progress and applications of antibody repertoire sequencing%大数据:基于高通量测序的抗体组学发展与应用

    Institute of Scientific and Technical Information of China (English)

    张在宝; 管茜; 张镇海

    2015-01-01

    Antibody, the major effector in adaptive immunity, plays key roles in protective and pathogenic immune responses. Integrative analyses of antibody development, differentiation, and maturation promote the research in immune mechanism, vaccine design, and therapies for autoimmune disorders. The development of next generation sequencing technologies has enabled large-scale characterization of functional antibody repertoires. With the advantages of next generation sequencing, antibody and antibody repertoire analysis have been successfully used in identification of HIV-1-broadly neutralizing antibodies, design of rationale structure-based vaccine, and development of immunology. With increasing sequence length and precision, improvement of experimental protocols and bioinformatics analyses, and development of single cell sequencing technology, antibody repertoire sequencing will expedite the research in antibody-related immune response, and thus facilitates vaccine design for infectious diseases, clinical diagnosis and interference of autoimmune diseases. This review introduces the technologies, progresses, applications, and caveats of antibody repertoire sequencing.%抗体是获得性免疫系统的主要组分,在防御性及致病性免疫反应中起着关键作用。对抗体发生、发展和成熟过程的解析,对研究传染性疾病致病机制、疫苗设计、自免疫疾病发生及进展等有着重要意义。随着高通量测序技术的发展和成熟,抗体研究进入了组学时代。通过对艾滋病患者外周血抗体谱的高通量测序及后续大数据分析挖掘已经在HIV-1广谱抗体研究中取得了丰硕的成果。随着测序技术的进一步发展、测序长度的增加及精度的提高、实验体系的优化、分析流程标准的建立及单细胞抗体测序技术的应用,抗体组学研究前景广阔。本文就抗体组学的技术、发展、应用及问题作简要综述。

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

    Science.gov (United States)

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

    2016-01-01

    Despite their wide use as therapeutic, diagnostic and detection agents, the limitations of polyclonal and monoclonal antibodies have inspired scientists to design the next generation biomedical agents, so-called antibody mimetics that offer many advantages over conventional antibodies. Antibody mimetics can be constructed by protein-directed evolution or fusion of complementarity-determining regions through intervening framework regions. Substantial progress in exploiting human, butterfly (Pieris brassicae) and bacterial systems to design and select mimetics using display technologies has been made in the past 10 years, and one of these mimetics [Kalbitor® (Dyax)] has made its way to market. Many challenges lie ahead to develop mimetics for various biomedical applications, especially those for which conventional antibodies are ineffective, and this review describes the current characteristics, construction and applications of antibody mimetics compared to animal-sourced antibodies. The possible limitations of mimetics and future perspectives are also discussed. PMID:25264572

  6. 黄曲霉毒素新型抗体制备研究进展%Research progress of aflatoxin B1 antibody preparation

    Institute of Scientific and Technical Information of China (English)

    江涛; 马良; 张宇昊; 吴春生; 蒋黎艳; 戴芳芳

    2014-01-01

    免疫学检测方法具有快捷、灵敏、特异性高的特点,在毒素的定量和定性方面已获得了快速的发展,成为毒素检测方法的研究热点。而高质量抗体的制备是建立特异性强、灵敏度高的免疫分析方法关键。目前主流研究和应用的抗体是单克隆抗体,其性质稳定,特异性强,灵敏度高。随着抗体技术的发展,重组抗体在免疫检测领域也逐渐应用。与多克隆抗体、单克隆抗体相比较而言,重组抗体具有独特的优势,可以在原核表达体系里短时间内大量生产且生产费用低廉,对黄曲霉毒素的低成本、大规模检测有重要的应用价值。本文重点阐述和分析了黄曲霉毒素单克隆抗体、重组抗体制备过程中存在的影响因素及问题,并对未来黄曲霉毒素抗体的发展前景进行了展望。%Immunological detection methods with fast, sensitive and highly specific characteristics had gained a rapid development and become a hot detection methods. High quality antibody was the key of aflatoxins determination by specific and sensitive immunoassay methods. Monoclonal antibody was the most popular antibody in current researches and commercial products for their stability, high specificity and high sensitivity. More and more recombinant antibodies were researched and applied with the development of antibody technology. Compared to these two types of antibodies, an abundance of recombinant antibody can be produced in prokaryotic expression systems in a very short time with low cost. It will be helpful to the low-cost and high throughput detection method of aflatoxins. In this paper, the preparation processing of monoclonal and recombinant antibodies in aflatoxin detection were summarized and the key factors in the preparation of aflatoxins antibody were analyzed.

  7. Detection of Serum Antibodies to Ovine Progressive Pneumonia Virus in Sheep by Using a Caprine Arthritis-Encephalitis Virus Competitive-Inhibition Enzyme-Linked Immunosorbent Assay

    OpenAIRE

    Herrmann, Lynn M.; Cheevers, William P.; Marshall, Katherine L.; McGuire, Travis C.; Hutton, Melinda M.; Lewis, Gregory S.; Knowles, Donald P

    2003-01-01

    A competitive-inhibition enzyme-linked immunosorbent assay (cELISA) for detection of antibodies to the surface envelope (SU) of caprine arthritis-encephalitis virus (CAEV) was recently reported (L. M. Herrmann, W. P. Cheevers, T. C. McGuire, D. Scott Adams, M. M. Hutton, W. G. Gavin, and D. P. Knowles, Clin. Diagn. Lab. Immunol. 10:267-271, 2003). The cELISA utilizes CAEV-63 SU captured on microtiter plates using the monoclonal antibody (MAb) F7-299 and measures competitive displacement of bi...

  8. Labelling, quality control and clinical evaluation of monoclonal antibodies for scintigraphy. Final report of a co-ordinated research programme 1991-1996

    International Nuclear Information System (INIS)

    Realizing the potential of labelled monoclonal antibodies for in vivo diagnosis and therapy and the interest in many developing Member States for acquiring expertise in this field the IAEA initiated a co-ordinated research programme in 1991 focusing on 99Tcm labelling of antibodies, their quality control and scintigraphic evaluation. Twelve laboratories from Asia, Latin America, Europe and North America participated in this programme which was concluded in 1996. During this programme the participants investigated the 99Tcm labelling of a murine anti-CEA antibody using the method of chelating 99Tcm with the free sulfhydryl groups generated by reaction with reducing agents such as mercapto ethanol. During the later part of the programme this method was also extended to 99Tcm labelling of hIgG. All the participating laboratories could gain valuable experience in 99Tcm antibody labelling techniques and formulation of kits. Many of them have been use in patients by collaborating nuclear medicine specialists with satisfactory results. This report is a compilation of the detailed results obtained by the participating laboratories and includes a summary and assessment of the achievement of the CRP

  9. Low-dose fractionated radiotherapy and concomitant chemotherapy for recurrent or progressive glioblastoma. Final report of a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Balducci, M.; Diletto, B.; Chiesa, S.; D' Agostino, G.R.; Gambacorta, M.A.; Ferro, M.; Valentini, V. [Catholic University of the Sacred Heart, Department of Radiation Oncology, Rome (Italy); Colosimo, C. [Catholic University of the Sacred Heart, Department of Radiology, Rome (Italy); Maira, G.; Anile, C. [Catholic University of the Sacred Heart, Department of Neurosurgery, Rome (Italy)

    2014-04-15

    Evaluated in this study were the feasibility and the efficacy of concurrent low dose fractionated radiotherapy (LD-FRT) and chemotherapy as palliative treatment for recurrent/progressive glioblastoma multiforme (GBM). Eligible patients had recurrent or progressive GBM, Karnofsky performance status ≥70, prior surgery, and standard radiochemotherapy treatment. Recurrence/progression disease during temozolomide (TMZ) received cisplatin (CDDP; 30 mg/m{sup 2} on days 1, 8, 15), fotemustine (FTM; 40 mg/m{sup 2} on days 2, 9, 16), and concurrent LD-FRT (0.3 Gy twice daily); recurrence/progression after 4 months from the end of adjuvant TMZ were treated by TMZ (150/200 mg/m{sup 2} on days 1-5) concomitant with LD-FRT (0.4 Gy twice daily). Primary endpoints were safety and toxicity. A total of 32 patients were enrolled. Hematologic toxicity G1-2 was observed in 18.7% of patients and G3-4 in 9.4%. One patient (3.1%) had complete response, 3 (9.4%) had partial response, 8 (25%) had stable disease for at least 8 weeks, while 20 patients (62.5%) experienced progressive disease. The clinical benefit was 37.5%. Median progression-free survival (PFS) and overall survival (OS) were 5 and 8 months, respectively. Survival rate at 12 months was of 27.8%. LD-FRT and chemotherapy for recurrent/progressive GBM have a good toxicity profile and clinical outcomes, even though further investigation of this novel palliative treatment approach is warranted. (orig.)

  10. Progress of the monoclonal antibody denosumab in breast cancer therapy%单克隆抗体Denosumab治疗乳腺癌的研究进展

    Institute of Scientific and Technical Information of China (English)

    战淑珺; 于忠和

    2011-01-01

    OBJECTIVE: To summarize the advance of Denosumab research in breast cancer treatment. METHODS: By PubMed and CNKI retrieval system, with“ Denosumab, breast neoplasms, osteoporosis, osseous metastases"as the key words, a total of 117 papers of literatures in English and 2 in Chinese were retrieved from 2004 to 2010. The articles that were repetitive studies and had no relations with the study were excluded, and 21 articles were included in reference study finally. RESULTS: Receptor activator of nuclear factor-κB ligand(RANKL) is found to be an essential mediator of osteoclast differentiation, fun-ction, and survival.The monoclonal antibody Denosumab binds and neutralizes RANKL. Some papers have evaluated the efficacy and safety of Denosumab in patients with osteo-porosis. Denosumab also is found to inhibit bone mineral resorption and increase bone density in the treatment of bone destruction and bone metastases caused by breast cancer, including reductions in markers of bone turnover, with no relevant severe adverse events. CONCLUSIONS: Denosumab have primarily been documented efficacy and safety as a potential treatment for bone destruction associated with breast cancer. Additional clinical trial is needed to completely establish the long-term followup survey,and the combination of Denosumab and the current therapies of breast cancer.%目的:总结Denosumab在乳腺癌相关治疗领域的应用研究进展.方法:应用PUBMED和CNKI期刊全文数据库检索系统,以"Denosumab,RANKL,乳腺肿瘤,骨质疏松,骨转移癌"等为关键词,检索2004-2010的相关文献.共检索到英文文献117篇,中文文献2篇,通过查找全文,排除重复研究及与本研究无关的文献,符合条件的21篇文献纳入分析.结果:单克隆抗体Denosumab靶向细胞核因子κB受体活化因子配基(receptor activator of nuclear factot-κB ligand,RANKL),可以特异性地阻断破骨细胞生成及存活,在治疗骨质疏松症及代谢性骨病中表现良

  11. Rapid isolation of antibody from a synthetic human antibody library by repeated fluorescence-activated cell sorting (FACS.

    Directory of Open Access Journals (Sweden)

    Sung Sun Yim

    Full Text Available Antibodies and their derivatives are the most important agents in therapeutics and diagnostics. Even after the significant progress in the technology for antibody screening from huge libraries, it takes a long time to isolate an antibody, which prevents a prompt action against the spread of a disease. Here, we report a new strategy for isolating desired antibodies from a combinatorial library in one day by repeated fluorescence-activated cell sorting (FACS. First, we constructed a library of synthetic human antibody in which single-chain variable fragment (scFv was expressed in the periplasm of Escherichia coli. After labeling the cells with fluorescent antigen probes, the highly fluorescent cells were sorted by using a high-speed cell sorter, and these cells were reused without regeneration in the next round of sorting. After repeating this sorting, the positive clones were completely enriched in several hours. Thus, we screened the library against three viral antigens, including the H1N1 influenza virus, Hepatitis B virus, and Foot-and-mouth disease virus. Finally, the potential antibody candidates, which show K(D values between 10 and 100 nM against the target antigens, could be successfully isolated even though the library was relatively small (∼ 10(6. These results show that repeated FACS screening without regeneration of the sorted cells can be a powerful method when a rapid response to a spreading disease is required.

  12. IgG subclass antibodies to human and bacterial HSP60 are not associated with disease activity and progression over time in axial spondyloarthritis

    DEFF Research Database (Denmark)

    Carlsen, Thomas Gelsing; Hjelholt, Astrid Johannesson; Jurik, Anne Grethe;

    2013-01-01

    and patient follow-up. In this study, we have focused on these parameters in a cohort of axial SpA patients with a well-established set of clinical characteristics, including MRI changes and human leukocyte antigen B27. METHODS: IgG subclass antibodies (IgG1, IgG2, IgG3 and IgG4) against recombinant HSP60...... and the disease parameters. RESULTS: Elevated levels of IgG1 and IgG3 to human HSP60 and IgG1 to HSP60 of Salmonella enterica Enteritidis were observed in SpA patients compared with healthy controls at both time points. The antibody levels were almost constant over time for IgG1, whereas high levels of IgG3...

  13. Final Technical Progress Report; Closeout Certifications; CSSV Newsletter Volume I; CSSV Newsletter Volume II; CSSV Activity Journal; CSSV Final Financial Report

    Energy Technology Data Exchange (ETDEWEB)

    Houston, Johnny L [PI; Geter, Kerry [Division of Business and Finance

    2013-08-23

    This Project?s third year of implementation in 2007-2008, the final year, as designated by Elizabeth City State University (ECSU), in cooperation with the National Association of Mathematicians (NAM) Inc., in an effort to promote research and research training programs in computational science ? scientific visualization (CSSV). A major goal of the Project was to attract the energetic and productive faculty, graduate and upper division undergraduate students of diverse ethnicities to a program that investigates science and computational science issues of long-term interest to the Department of Energy (DoE) and the nation. The breadth and depth of computational science?scientific visualization and the magnitude of resources available are enormous for permitting a variety of research activities. ECSU?s Computational Science-Science Visualization Center will serve as a conduit for directing users to these enormous resources.

  14. Final Progress Report for Collaborative Research: Aging of Black Carbon during Atmospheric Transport: Understanding Results from the DOE’s 2010 CARES and 2012 ClearfLo Campaigns

    Energy Technology Data Exchange (ETDEWEB)

    Mazzoleni, Claudio [Michigan Technological Univ., Houghton, MI (United States); Subramanian, R. [Carnegie Mellon Univ., Pittsburgh, PA (United States)

    2016-08-31

    Over the course of this project, we have analyzed data and samples from the Carbonaceous Aerosol and Radiative Effects Study (CARES) and the Clear air for London (ClearfLo) campaign, as well as conducted or participated in laboratory experiments designed to better understand black carbon mixing state and climate-relevant properties. The laboratory campaigns took place at the Pacific Northwest National Laboratory and Carnegie Mellon University to study various climate-relevant aerosol properties of different sources of soot mixing with secondary organic aerosol precursors. Results from some of these activities were summarized in the previous progress report. This final report presents the manuscripts that have been published (many in the period since the last progress report), lists presentations at different conferences based on grant-related activities, and presents some results that are likely to be submitted for publication in the near future.

  15. Fusion reactor systems studies. Progress report for the period November 1, 1996--October 31, 1997, and final report

    International Nuclear Information System (INIS)

    During FY97, the University of Wisconsin Fusion Technology Institute personnel have participated in the ARIES-RS and the ARIES-ST projects. The main areas of effort are: (1) neutronics analysis; (2) shielding of components and personnel; (3) neutron wall loading distribution; (4) radiation damage to in-vessel components; (5) components lifetimes; (6) embrittled materials designs issues; (7) stress and structural analysis; (8) activation, LOCA, and safety analysis; (9) support and fabrication of components; (10) vacuum system; and (11) maintenance. Progress made in these areas are summarized

  16. Fusion reactor systems studies. Progress report for the period November 1, 1996--October 31, 1997, and final report

    Energy Technology Data Exchange (ETDEWEB)

    El-Guebaly, L.A.; Blanchard, J.P.; Kulcinski, G.L.

    1997-08-01

    During FY97, the University of Wisconsin Fusion Technology Institute personnel have participated in the ARIES-RS and the ARIES-ST projects. The main areas of effort are: (1) neutronics analysis; (2) shielding of components and personnel; (3) neutron wall loading distribution; (4) radiation damage to in-vessel components; (5) components lifetimes; (6) embrittled materials designs issues; (7) stress and structural analysis; (8) activation, LOCA, and safety analysis; (9) support and fabrication of components; (10) vacuum system; and (11) maintenance. Progress made in these areas are summarized.

  17. Third annual progress report on the electrofluid dynamic wind generator. Final report, September 15, 1977-September 30, 1978

    Energy Technology Data Exchange (ETDEWEB)

    Minardi, J.E.; Lawson, M.O.; Wattendorf, F.L.

    1979-05-01

    The objective of the program is to conduct research leading to the development of EFD wind driven generators. In such generators, the wind blows through suitably oriented arrays of electrodes, transports charged particles against an electrical potential gradient, and thereby generates electrical power directly without moving parts. Significant progress has been made in accomplishing major research objectives. During the past year, the effort was directed toward the achievement of three milestones, namely: development of a laboratory method for the production of an adequate supply of suitably low mobility charged droplets for the testing of generator performance; experimental verification of generator performance theory; and development of methods for practical production of charged droplets.

  18. Antibodies immobilized on magnetic particles for radioimmunoassay and immunoradiometric assay of hormones. Final report of a co-ordinated research programme 1991-1995

    International Nuclear Information System (INIS)

    The IAEA organized a co-ordinated research programme (CRP) in 1991 for studying the properties of a few most promising magnetizable immunoadsorbents and standardizing some important radioimmunoassay and immunoradiometric assay procedures using them with the ultimate aim of expanding the application of these assays in developing countries using indigenously prepared reagents. Ten laboratories from nine countries of Asia, Latin America and Europe participated in this CRP which was concluded in 1995. Three different magnetizable particles prepared and investigated by the participants, namely magnetite, magnetite coated with silane and magnetite coated with polyacrolein, have emerged suitable for use in radioimmunometric assays from this CRP. Methods have been developed for coupling antibodies to these particles and using the resultant immunoadsorbents for assaying several important hormones and proteins including T3, T4, fT3, fT4, reverse T3, TSH, thyroglobuling(Tg), Tg-antibodies, HCG, LH, cortisol, FSH and prolacting. All the participating laboratories could develop in house methodology for solid phase assays based on magnetizable particles during the course of the CRP and benefit from the exchange of materials, information and experience amongst them. This report includes detailed results obtained by the participating laboratories as well as a summary and assessment of the achievements of the CRP. It also includes suggestions for areas of investigation for pursuing in the future. Refs, figs, tabs

  19. Final Progress Report: FRACTURE AND SUBCRITICAL DEBONDING IN THIN LAYERED STRUCTURES: EXPERIMENTS AND MULTI-SCALE MODELING

    Energy Technology Data Exchange (ETDEWEB)

    Reinhold H. Dauskardt

    2005-08-30

    Final technical report detailing unique experimental and multi-scale computational modeling capabilities developed to study fracture and subcritical cracking in thin-film structures. Our program to date at Stanford has studied the mechanisms of fracture and fatigue crack-growth in structural ceramics at high temperature, bulk and thin-film glasses in selected moist environments where we demonstrated the presence of a true mechanical fatigue effect in some glass compositions. We also reported on the effects of complex environments and fatigue loading on subcritical cracking that effects the reliability of MEMS and other micro-devices using novel micro-machined silicon specimens and nanomaterial layers.

  20. Research progress in treatment of metastatic colorectal cancer with EGFR monoclonal antibody%EGFR单抗治疗转移性结直肠癌的研究进展

    Institute of Scientific and Technical Information of China (English)

    李晓佳; 韩宇; 黄鹏; 李燕京; 白玉贤

    2013-01-01

    Epidermal growth factor receptor(EGFR) monoclonal antibody is increasingly important in the treatment of metastatic colorectal cancer. Monoclonal antibody, especially, cetuximab and panitumumab have a high efficiency opposed to the uselessness of chemotherapy. In this paper, we provide several clinical trials to explored that either first-line or second-line and preoperative chemotherapy, EGFR monoclonal antibody in combination with chemotherapy maybe superior to anti-EGFR monoclonal alone to extend survival for patient with metastatic colorectal cancer. In order to improve the curative effect, the bio-maker researches is necessary for individualized treatment, such as EGFR GCN and KRAS, BRAF, PIK3CAin the downstream of the EGFR signal pathway. The aim of this paper is to introduce the research progress about the EGFR monoclonal antibody.%目前随着晚期结直肠癌分子生物学研究的不断深入,表皮生长因子受体(EGFR)单抗在转移性结直肠癌的治疗中变得尤为重要,尤其是西妥昔单抗和帕尼单抗,在标准化疗方案失败的患者中具有很高的疗效。大量临床试验表明,在晚期结直肠癌的治疗中,无论一线、二线抑或是转化化疗,标准化疗方案联合EGFR单抗靶向药物治疗的疗效均优于单纯化疗。为了进一步筛检EGFR单抗疗效的有效性,对相关基因研究的结果为此提供了依据,例如 EGFR 基因拷贝量的多少,及其下游通路的 KRAS,BRAF, PIK3CA基因的状态等。本文结合最新报道,就EGFR单抗治疗转移性结直肠癌的疗效及预测因子做一综述。

  1. Progress in anti-CD20 monoclonal antibodies and their clinical application%抗CD20单抗的研究进展及其临床应用

    Institute of Scientific and Technical Information of China (English)

    梁碧华; 樊翌明; 朱慧兰

    2011-01-01

    Anti-CD20 monoclonal antibodies have been applied to the treatment of many autoimmune diseases and severe urticaria with favourable outcomes. Current researches about anti-CD20 monoclonal antibodies are focused on their application in refractory urticaria such as autoimmune urticaria and urticarial vasculitis. Their mechanism of action has not been defined. B cell depletion mechanism is considered to be associated with complement-dependent cytotoxicity, antibody dependent cellular cytotoxicity, direct induction of apoptosis, etc. This paper outlines the progress in researches on anti-CD20 monoclonal antibodies and their application in autoimmune diseases and urticaria, in order to provide evidence for their use in urticaria, and to predict their perspectives in the treatment of refractory urticaria.%抗CD20单克隆抗体目前已用于治疗较多的自身免疫性疾病,并有研究将其用于严重荨麻疹的治疗,且取得良好疗效.但相关的研究主要局限在自身免疫性荨麻疹或荨麻疹性血管炎等难治性荨麻疹中的应用,其作用机制尚未明确.B细胞清除机制认为与补体依赖性细胞毒性反应、抗体依赖细胞介导的细胞毒作用及直接诱导B淋巴细胞凋亡等有关.概述抗CD20单克隆抗体目前的研究进展及其在自身免疫性疾病和荨麻疹中的临床应用,旨在进一步揭示其可用于荨麻疹治疗的证据,从而更好地了解其在难治性荨麻疹中应用的前景.

  2. Measurement and apportionment of radon source terms for modeling indoor environments. Final progress report, March 1990--August 1992

    Energy Technology Data Exchange (ETDEWEB)

    Harley, N.H.

    1992-12-31

    During the present 2 1/2 year contract period, we have made significant Progress in modeling the source apportionment of indoor {sup 222}Rn and in {sup 222}Rn decay product dosimetry. Two additional areas were worked on which we believe are useful for the DOE Radon research Program. One involved an analysis of the research house data, grouping the hourly house {sup 222}Rn measurements into 2 day, 7 day and 90 day intervals to simulate the response of passive monitors. Another area requiring some attention resulted in a publication of 3 years of our indoor/outdoor measurements in a high-rise apartment. Little interest has been evinced in apartment measurements yet 20% of the US population lives in multiple-family dwellings, not in contact with the ground. These data together with a summary of all other published data on apartments showed that apartments have only about 50% greater {sup 222}Rn concentration than the measured outdoor {sup 222}Rn. Apartment dwellers generally represent a low risk group regarding {sup 222}Rn exposure. The following sections describe the main projects in some detail.

  3. Engineering support services for the DOE/GRI coal gasification research program. Final technical progress report, October 1978-November 1982

    Energy Technology Data Exchange (ETDEWEB)

    Bostwick, L.E.

    1982-01-01

    The agreement between the United States Government Department of Energy and the Gas Research Institute for the Joint Coal Gasification Research Program provided for one or more technical evaluation contractors. Pullman Kellogg (now the M.W. Kellogg Company) was selected as evaluation contractor to assess, and report to the DOE/GRI Operating Committee on, the relative merits of the active programs covered by the agreement. This report includes the period from 1 October 1978 to 30 November 1982. The objective was to provide engineering support for the DOE/GRI high Btu coal gasification program. This support generally consisted of assistance in developing or advancing each process to its maximum potential. Kellogg monitored and evaluated the startup and operational activities of all pilot plant projects within the combined DOE/GRI program. Kellogg evaluated proposals to determine their technical feasibility as potential processes or as viable processing operations for commercial-scale gasification of coal. Kellogg also recorded observations on the reliability, maintainability, and availability of the equipment used in the pilot plant or PDU facilities. Kellogg performed design reviews, data analyses, and engineering evaluations of proposals, cost estimates and monthly progress reports to provide information considered essential to the overall objectives of the combined DOE/GRI program.

  4. Advances in monoclonal antibody application in myocarditis

    Institute of Scientific and Technical Information of China (English)

    Li-na HAN; Shuang HE; Yu-tang WANG; Li-ming YANG; Si-yu LIU; Ting ZHANG

    2013-01-01

    Monoclonal antibodies have become a part of daily preparation technologies in many laboratories.Attempts have been made to apply monoclonal antibodies to open a new train of thought for clinical treatments of autoimmune diseases,inflammatory diseases,cancer,and other immune-associated diseases.This paper is a prospective review to anticipate that monoclonal antibody application in the treatment of myocarditis,an inflammatory disease of the heart,could be a novel approach in the future.In order to better understand the current state of the art in monoclonal antibody techniques and advance applications in myocarditis,we,through a significant amount of literature research both domestic and abroad,developed a systematic elaboration of monoclonal antibodies,pathogenesis of myocarditis,and application of monoclonal antibodies in myocarditis.This paper presents review of the literature of some therapeutic aspects of monoclonal antibodies in myocarditis and dilated cardiomyopathy to demonstrate the advance of monoclonal antibody application in myocarditis and a strong anticipation that monoclonal antibody application may supply an effective therapeutic approach to relieve the severity of myocarditis in the future.Under conventional therapy,myocarditis is typically associated with congestive heart failure as a progressive outcome,indicating the need for alternative therapeutic strategies to improve long-term results.Reviewing some therapeutic aspects of monoclonal antibodies in myocarditis,we recently found that monoclonal antibodies with high purity and strong specificity can accurately act on target and achieve definite progress in the treatment of viral myocarditis in rat model and may meet the need above.However,several issues remain.The technology on howto make a higher homologous and weak immunogenic humanized or human source antibody and the treatment mechanism of monoclonal antibodies may provide solutions for these open issues.If we are to further stimulate

  5. Construction of a genome-wide human BAC-Unigene resource. Final progress report, 1989--1996

    Energy Technology Data Exchange (ETDEWEB)

    Lim, C.S.; Xu, R.X.; Wang, M. [and others

    1996-12-31

    Currently, over 30,000 mapped STSs and 27,000 mapped Unigenes (non-redundant, unigene sets of cDNA representing EST clusters) are available for human alone. A total of 44,000 Unigene cDNA clones have been supplied by Research Genetics. Unigenes, or cDNAs are excellent resource for map building for two reasons. Firstly, they exist in two alternative forms -- as both sequence information for PCR primer pairs, and cDNA clones -- thus making library screening by colony hybridization as well as pooled library PCR possible. The authors have developed an efficient and robust procedure to screen genomic libraries with large number of DNA probes. Secondly, the linkage and order of expressed sequences, or genes are highly conserved among human, mouse and other mammalian species. Therefore, mapping with cDNA markers rather than random anonymous STSs will greatly facilitate comparative, evolutionary studies as well as physical map building. They have currently deconvoluted over 10,000 Unigene probes against a 4X coverage human BAC clones from the approved library D by high density colony hybridization method. 10,000 batches of Unigenes are arrayed in an imaginary 100 X 100 matrix from which 100 row pools and 100 column pools are obtained. Library filters are hybridized with pooled probes, thus reducing the number of hybridization required for addressing the positives for each Unigene from 10,000 to 200. Details on the experimental scheme as well as daily progress report is posted on the Web site (http://www.tree.caltech.edu).

  6. The oncogenic action of ionizing radiation on rat skin. Final progress report, May 1, 1990--April 30, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Burns, F.J.; Garte, S.J.

    1992-12-31

    The multistage theory of carcinogenesis specifies that cells progress to cancer through a series of discrete, irreversible genetic alterations, but data on radiation-induced cancer incidence in rat skin suggests that an intermediate repairable alteration may occur. Data are presented on cancer induction in rat skin exposed to an electron beam (LET=0.34 keV/{mu}), a neon ion beam (LET=45) or an argon ion beam (LET=125). The rats were observed for tumors at least 78 weeks with squamous and basal cell carcinomas observed. The total cancer yield was fitted by the quadratic equation, and the equation parameters were estimated by linear regression for each type of radiation. Analysis of the DNA from the electron-induced carcinomas indicated that K-ras and/or c-myc oncogenes were activated. In situ hybridization indicated that the cancers contain subpopulations of cells with differing amounts of c-myc and H-ras amplification. The results are consistent with the idea that ionizing radiation produces stable, carcinogenically relevant lesions via 2 repairable events at low LET and via a non-repairable linked event pathway at high LET; either pathway may advance the cell by 1 stage. The proliferative response of rat epidermis following exposure to ionizing radiation was quantified by injection of {sup 14}C-thymidine. The return of these cells to S-phase a second time was detected by a second label ({sup 3}H). When the labeled cells were in G1-phase, the dorsal skin was irradiated with X-rays. All labeling indices were determined. The {sup 14}C labeling index was constant and unaffected by the radiation. The proportion of all cells entering S-phase averaged 3.5% at 18 hr and increased after 44, 52 and 75 hr to average levels of 11.8%, 5. 3%, and 6.6% at 0, 10 and 25 Gy respectively. The proportion of S-phase cells labeled with {sup 14}C increased after 42 hr and remained relatively constant thereafter.

  7. Hybrid solar thermal-photovoltaic systems demonstration, Phase I and II. Final technical progress report, July 5, 1979-December 1982

    Energy Technology Data Exchange (ETDEWEB)

    Loferski, J.J. (ed.)

    1983-12-01

    The purpose of the project is to investigate a system based on combined photovoltaic/thermal (PV/T) panels to supply the energy needs of a small single family residence. The system finally selected and constructed uses PV/T panels which utilize air as the heat transfer medium. Optimization of thermal performance was accomplished by attaching metal fins to the back surface of each cell which significantly increased the heat transfer coefficient from the solar cells to the air stream. The other major components of the selected system are an air-to-air heat pump, a rock bin thermal energy storage bin, a synchronous dc-to-ac converter, a microprocessor to control the system, a heat exchanger for the domestic hot water system and of course the building itself which is a one story, well insulated structure having a floor area of 1200 ft/sup 2/. A prototype collector was constructed and tested. Based on this experience, twenty collectors, containing 2860 four inch diameter solar cells, were constructed and installed on the building. Performance of the system was simulated using a TRNSYS-derived program, modified to accommodate PV/T panels and to include the particular components included in the selected system. Simulation of the performance showed that about 65 percent of the total annual energy needs of the building would be provided by the PV/T system. Of this total, about one half is produced at a time when it can be used in the building and one half must be sold back to the utility.

  8. Shorebird Project Final Progress Report

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This study documented the habitats, hydrology, vegetation communities and weather patterns that create or destroy shorebird habitat. This project examined shorebird...

  9. ROCK DEFORMATION. Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    None

    2002-05-24

    The Gordon Research Conference (GRC) on ROCK DEFORMATION was held at II Ciocco from 5/19/02 thru 5/24/02. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  10. Antibodies to watch in 2014.

    Science.gov (United States)

    Reichert, Janice M

    2014-01-01

    Since 2010, mAbs has documented the biopharmaceutical industry's progress in transitioning antibody therapeutics to first Phase 3 clinical studies and regulatory review, and its success at gaining first marketing approvals for antibody-based products. This installment of the "Antibodies to watch" series outlines events anticipated to occur between December 2013 and the end of 2014, including first regulatory actions on marketing applications for vedolizumab, siltuximab, and ramucirumab, as well as the Fc fusion proteins Factor IX-Fc and Factor VIII-Fc; and the submission of first marketing applications for up to five therapeutics (secukinumab, ch14.18, onartuzumab, necitumumab, gevokizumab). Antibody therapeutics in Phase 3 studies are described, with an emphasis on those with study completion dates in 2014, including antibodies targeting interleukin-17a or the interleukin-17a receptor (secukinumab, ixekizumab, brodalumab), proprotein convertase subtilisin/kexin type 9 (alirocumab, evolocumab, bococizumab), and programmed death 1 receptor (lambrolizumab, nivolumab). Five antibodies with US Food and Drug Administration's Breakthrough Therapy designation (obinutuzumab, ofatumumab, lambrolizumab, bimagrumab, daratumumab) are also discussed. PMID:24284914

  11. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Estep, Donald [Colorado State University

    2015-11-30

    This is the final report for the project titled "Enabling Predictive Simulation and UQ of complex Multiphysics PDE systems by the Development of Goal-Oriented Variational Sensitivity Analysis and a-Posteriori Error Estimation Methods" that ran from 9/1/2010 through 8/31/2015. The report describes the scientific progress, all manuscripts, and records project-related activities.

  12. Monoclonal antibodies

    International Nuclear Information System (INIS)

    Monoclonal antibodies (MAbs) are antibodies having single specificity for a given antigen site (epitope). The development of hybridoma technology and the relative ease by which MAbs can be prepared has revolutionized many aspects of serological applications in diagnosis and differentiation of disease producing agents. The property of monospecificity offers advantages in diagnostic applications over polyclonal sera in that tests can be defined exactly with regard to the antigen detected and the affinity of reaction between the given antigenic site and the monoclonal reagent. In addition, MAbs offer better possibilities for test standardization, because the same reagent can be used in different laboratories. Such an MAb can be supplied by a central laboratory or 'grown' from hybridoma cells, ensuring that the resultant product is identical from laboratory to laboratory and that the part of the test involving the MAb reaction is the same. The methodologies for inoculation regimes, mice, cloning methods, selection of fusion partners, etc., have been validated extensively in developed country laboratories. The decision to establish a MAb production facility must be examined on a strict cost-benefit basis, since it is still expensive to produce a product. There are many MAbs available that should be sought to allow exploitation in developing tests. If a production facility is envisaged, it should produce reagents for national needs, i.e. there should be a clear problem oriented approach whereby exact needs are defined. In the field of veterinary applications, MAbs are the central reagent in many immunoassays based on the enzyme linked immunosorbent assay (ELISA). The development of specific tests for diagnosing diseases is dominated by MAbs and has been fuelled by a strong research base, mainly in developed countries allied to developing countries through the study of related diseases. Thus, there are very many assays dependent on MAbs, some of which form the basis of

  13. γ-Synuclein Antibodies Have Neuroprotective Potential on Neuroretinal Cells via Proteins of the Mitochondrial Apoptosis Pathway

    OpenAIRE

    Corina Wilding; Katharina Bell; Sabine Beck; Sebastian Funke; Norbert Pfeiffer; Grus, Franz H.

    2014-01-01

    The family of synuclein proteins (α, β and γ) are related to neurodegenerative disease e.g. Parkinson disease and Morbus Alzheimer. Additionally, a connection between γ-synuclein and glaucoma, a neurodegenerative disease characterized by a progressive loss of retinal ganglion cells, which finally leads to blindness, exists. The reason for the development of glaucoma is still unknown. Recent studies evaluating the participation of immunological components, demonstrate complex changed antibody ...

  14. Monoclonal antibodies.

    Science.gov (United States)

    2009-01-01

    The ability to produce and exploit monoclonal antibodies (mAbs) has revolutionized many areas of biological sciences. The unique property of an mAb is that it is a single species of immunoglobulin (IG) molecule. This means that the specificity of the interaction of the paratopes on the IG, with the epitopes on an antigenic target, is the same on every molecule. This property can be used to great benefit in immunoassays to provide tests of defined specificity and sensitivity, which improve the possibilities of standardization. The performance of assays can often be determined relating the actual weight of antibody (hence the number of molecules) to the activity. Often the production of an mAb against a specific epitope is the only way that biological entities can be differentiated. This chapter outlines the areas involving the development of assays based on mAbs. The problems involved address include the physical aspects of mAbs and how they may affect assay design and also the implications of results based on monospecific reagents. Often these are not fully understood, leading to assays that are less than satisfactory, which does not justify the relatively high cost of preparing and screening of mAbs. There are many textbooks and reviews dealing with the preparation of mAbs, the principles involved, and various purification and manipulative methods for the preparation of fragments and conjugation. There has been little general information attempting to summarize the best approaches to assay design using mAbs. Much time can be wasted through bad planning, and this is particularly relevant to mAbs. A proper understanding of some basic principles is essential. It is beyond the scope of this chapter to discuss all aspects, but major areas are highlighted. PMID:19219589

  15. Back to the future: recombinant polyclonal antibody therapeutics.

    Science.gov (United States)

    Wang, Xian-Zhe; Coljee, Vincent W; Maynard, Jennifer A

    2013-11-01

    Antibody therapeutics are one of the fastest growing classes of pharmaceuticals, with an annual US market over $20 billion, developed to treat a variety of diseases including cancer, auto-immune and infectious diseases. Most are currently administered as a single molecule to treat a single disease, however there is mounting evidence that cocktails of multiple antibodies, each with a unique binding specificity and protective mechanism, may improve clinical efficacy. Here, we review progress in the development of oligoclonal combinations of antibodies to treat disease, focusing on identification of synergistic antibodies. We then discuss the application of modern antibody engineering technologies to produce highly potent antibody preparations, including oligoclonal antibody cocktails and truly recombinant polyclonal antibodies. Specific examples illustrating the synergy conferred by multiple antibodies will be provided for diseases caused by botulinum toxin, cancer and immune thrombocytopenia. The bioprocessing and regulatory options for these preparations will be discussed. PMID:24443710

  16. 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.

  17. [Antinuclear antibodies].

    Science.gov (United States)

    Cabiedes, Javier; Núñez-Álvarez, Carlos A

    2010-01-01

    Anti-nuclear antibodies (ANA) are immunoglobulin directed against autologous cell nuclear and cytoplasmic components. Besides the autoimmune ANA there are other ANA that can be detected in circulation, like natural and infectious ANA. Because of its high sensibility, detection of the ANA must be done by indirect immunofluorescence (IIF) as screening test and all of those positive samples are convenient to confirm its specificity by ELISA, western blot or other techniques. Positive ANA detected by IIF must be evaluated taking in to account the pattern and titer. The following recommended step is the specificity characterization (reactivity against extractable nuclear antigens [ENA], dsDNA, etc.) which is useful for the diagnosis and follow up of patients with autoimmune diseases, and by such reasoning, its detection must be performed in an orderly and reasonable way using guides or strategies focused to the good use and interpretation of the autoantibodies. The objective of this review is to present a compilation of the literature and our experience in the detection and study of the ANA.

  18. 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.

  19. The antibody approach of labeling blood cells

    International Nuclear Information System (INIS)

    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

  20. 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.

  1. 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.

  2. 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. PMID:15844826

  3. Virus-specific antibodies in sera from patients with genital herpes simplex virus infection.

    OpenAIRE

    Zweerink, H J; Corey, L

    1982-01-01

    Virus-specific antibodies against a number of herpes simplex virus type 2 antigens were determined by radioimmunoprecipitation assays in sequential serum samples obtained from 12 patients with initial genital herpes simplex virus infection. The progressive appearance of antibodies to virus-specific antigens was observed; antibodies against a 130,000-molecular-weight glycoprotein complex appeared first, followed by antibodies against the major nucleocapsid polypeptide and then antibodies again...

  4. B cells contribute to MS pathogenesis through antibody-dependent and antibody-independent mechanisms

    Directory of Open Access Journals (Sweden)

    Wilson HL

    2012-05-01

    Full Text Available Heather L Wilson1,21Vaccine and Infectious Disease Organization-International Vaccine Center, 2Department of Biochemistry, University of Saskatchewan, Saskatoon, Saskatchewan, CanadaAbstract: For many years, central dogma defined multiple sclerosis (MS as a T cell-driven autoimmune disorder; however, over the past decade there has been a burgeoning recognition that B cells contribute to the pathogenesis of certain MS disease subtypes. B cells may contribute to MS pathogenesis through production of autoantibodies (or antibodies directed at foreign bodies, which unfortunately cross-react with self-antigens, through promotion of T cell activation via antigen presentation, or through production of cytokines. This review highlights evidence for antibody-dependent and antibody-independent B cell involvement in MS pathogenesis.Keywords: autoantibodies, antibody targets, clinically isolated MS, primary progressive MS, secondary progressive MS, relapsing and remitting MS, T cells, T regulatory cells

  5. Antibody-mediated Xenograft Injury: Mechanisms and Protective Strategies

    OpenAIRE

    Pierson, Richard N.

    2009-01-01

    The use of porcine organs for clinical transplantation is a promising potential solution to the shortage of human organs. Preformed anti-pig antibody is the primary cause of hyperacute rejection, while elicited antibody can contribute to subsequent “delayed” xenograft rejection. This article will review recent progress to overcome antibody mediated xenograft rejection, through modification of the host immunity and use of genetically engineered pig organs.

  6. Pharmacokinetics interactions of monoclonal antibodies.

    Science.gov (United States)

    Ferri, Nicola; Bellosta, Stefano; Baldessin, Ludovico; Boccia, Donatella; Racagni, Giorgi; Corsini, Alberto

    2016-09-01

    The clearance of therapeutic monoclonal antibodies (mAbs) typically does not involve cytochrome P450 (CYP450)-mediated metabolism or interaction with cell membrane transporters, therefore the pharmacokinetics interactions of mAbs and small molecule drugs are limited. However, a drug may affect the clearance of mAbs through the modulation of immune response (e.g., methotrexate reduces the clearance of infliximab, adalimumab, and golimumab, possibly due to methotrexate's inhibitory effect on the formation of antibodies against the mAbs). In addition, mAbs that are cytokine modulators may modify the metabolism of drugs through their effects on P450 enzymes expression. For example, cytokine modulators such as tocilizumab (anti-IL-6 receptor antibody) may reverse the "inhibitory" effect of IL-6 on CYP substrates, resulting in a "normalization" of CYP activities. Finally, a drug may alter the clearance of mAbs by either increasing or reducing the levels of expression of targets of mAbs on the cell surface. For instance, statins and fibrates induce PCSK9 expression and therefore increase cellular uptake and clearance of alirocumab and evolocumab, anti-PCSK9 antibodies. In the present review, we will provide an overview on the pharmacokinetics properties of mAbs as related to the most relevant examples of mAbs-small molecule drug interaction.

  7. JDIP Genomics, Antibodies, and Proteomics Core Update

    Science.gov (United States)

    The JDIP Genomics, Proteomics, and Antibodies Core has developed several resources that are available for use by JDIP researchers. Five tasks have been completed or are in progress: Task 1 – Transposon mutants: Nearly 24,000 gene disruption M. paratuberculosis mutants are now available for JDIP re...

  8. The progress of monoclonal antibodies applied in the diagnosis of classical swine fever%猪瘟单克隆抗体诊断方法的研究概述

    Institute of Scientific and Technical Information of China (English)

    李娇; 王艳; 唐娜; 沈志强

    2011-01-01

    猪瘟单克隆抗体以其敏感性高、特异性强、能够识别病毒抗原结构的微小差异,同时单抗特有的理化同质性使抗原抗体反应结果便于质量控制、利于标准化和规范化等优点,在猪瘟病毒的诊断以及强弱毒鉴别诊断中得到了广泛应用,显示出良好的应用前景。本文就猪瘟单克隆抗体及其在猪瘟诊断中的应用进展作一综述。%CSF monoclonal antibody of its high sensitivity and specificity,can identify small differences in the structure of viral antigen,while monoclonal antibody specific to the physical and chemical homogeneity of the antigen-antibody reaction results to facilitate quality control,standardization and standardized benefit advantages, such as classical swine fever virus diagnosis and differential diagnosis of attenuated intensity is widely used, showing a good prospect.In this paper, monoelonal antibodies to classical swine fever and its application in diagnosis are reviewed.

  9. Experimental verification of a progressive damage model for composite laminates based on continuum damage mechanics. M.S. Thesis Final Report

    Science.gov (United States)

    Coats, Timothy William

    1994-01-01

    Progressive failure is a crucial concern when using laminated composites in structural design. Therefore the ability to model damage and predict the life of laminated composites is vital. The purpose of this research was to experimentally verify the application of the continuum damage model, a progressive failure theory utilizing continuum damage mechanics, to a toughened material system. Damage due to tension-tension fatigue was documented for the IM7/5260 composite laminates. Crack density and delamination surface area were used to calculate matrix cracking and delamination internal state variables, respectively, to predict stiffness loss. A damage dependent finite element code qualitatively predicted trends in transverse matrix cracking, axial splits and local stress-strain distributions for notched quasi-isotropic laminates. The predictions were similar to the experimental data and it was concluded that the continuum damage model provided a good prediction of stiffness loss while qualitatively predicting damage growth in notched laminates.

  10. Monoclonal antibodies and cancer

    International Nuclear Information System (INIS)

    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 111In, 67Ga and 131I. 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

  11. Federal Assistance Program Quarterly Project Progress Report. Geothermal Energy Program: Information Dissemination, Public Outreach, and Technical Analysis Activities. Reporting Period: January 1 - March 31, 2001 [Final report

    Energy Technology Data Exchange (ETDEWEB)

    Lund, John W.

    2002-03-22

    The final report of the accomplishments of the geothermal energy program: information dissemination, public outreach and technical analysis activities by the project team consisting of the Geo-Heat Center, Geothermal Resources Council, Geothermal Education Office, Geothermal Energy Association and the Washington State University Energy Program.

  12. [VGKC-complex antibodies].

    Science.gov (United States)

    Watanabe, Osamu

    2013-04-01

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

  13. Anti-neutrophil cytoplasmic antibody-associated Pauci-immune crescentic glomerulonephritis complicating Sjögren's syndrome.

    Science.gov (United States)

    Wang, Wei-Jei; Wu, Hau-Shin; Chu, Tzong-Shinn

    2011-07-01

    Sjögren's syndrome is a chronic autoimmune disease, characterized by specific autoimmune antibodies anti-Ro and anti-La, and it can involve multiple organs, such as the kidneys, lungs, muscles, and nervous system. The most common renal complication of Sjögren's syndrome is tubulointerstitial nephritis, and glomerulonephritis is relatively uncommon. We report the case of an 86-year-old man presenting with recurrent fever, poor appetite, decreased salivary secretion, and body weight loss. Laboratory investigation revealed that serum creatinine was 4.2 mg/dL, proteinuria was 3+, and there was microscopic hematuria. Positive perinuclear anti-neutrophil cytoplasmic antibody, anti-Ro, and anti-La antibodies were detected. Renal biopsy showed crescentic glomerulonephritis with scanty immune complex deposition. The patient was diagnosed with primary Sjögren's syndrome complicated with rapidly progressive glomerulonephritis with positive anti-neutrophil cytoplasmic antibody. Unlike the patients of other case reports, our patient's renal function did not recover after immunosuppressant treatment, and he finally received long-term hemodialysis. Pauci-immune glomerulonephritis is a rare renal complication of Sjögren's syndrome, and progress to renal failure in such patients is possible.

  14. Progress of monoclonal antibody secretion hybridoma cell rapid screening technology based on HTS-ELISA%基于HTS-ELISA的单克隆抗体分泌杂交瘤细胞筛选技术进展

    Institute of Scientific and Technical Information of China (English)

    甄玉萍; 裴世春; 高建伟

    2014-01-01

    Various immune analysis technologies based on the monoclonal antibody are the main develop-ment direction for modern food safety rapid detection technology. Therefore, preparation of monoclonal anti-bodies with high-activity has got more and more attention by researchers. Preparation of monoclonal antibody usually involves many techniques, including the preparation of the antigen, immune design, cell fusion, screening of active hybridoma and antibody purification. Among them, the screening of monoclonal antibody secreting hybridoma cells is a key of the prepared monoclonal antibody part. Therefore, in order to provide a reference for high-activity monoclonal antibody preparation and the development of rapid detection technology for food safety, this paper focused on low density fusion cell culture, special equipment and the principle and technology of determining hybridoma cell activity in the screening process according to drag the number of holes (Trailing) to related activities, and mainly introduced one kind of high-activity monoclonal antibody se-cretion hybridoma technique which was based on HTS-ELISA screening method.%基于单克隆抗体的各类免疫分析技术是现代食品安全快速检测技术发展的主要方向之一,因此,高活性单克隆抗体的制备方法自然为众多研究者所关注。通常单克隆抗体的制备过程涉及到很多技术环节,包括抗原制备、免疫剂量设计、细胞融合、活性杂交瘤细胞筛选以及抗体纯化等,其中分泌单克隆抗体杂交瘤细胞的筛选环节是单克隆抗体制备的关键一环。为此,本文主要介绍了一种基于HTS-ELISA的高活性单克隆抗体分泌杂交瘤细胞的筛选技术,重点是对融合细胞的低密度培养、特殊仪器设备和在筛选过程中如何依据拖孔数(Trailing)来判断杂交瘤细胞的活性等相关的原理和技术,旨在为我国高活性单克隆抗体制备技术的发展及加快食品安全快

  15. Targeting Tumor Cells with Anti-CD44 Antibody Triggers Macrophage-Mediated Immune Modulatory Effects in a Cancer Xenograft Model.

    Science.gov (United States)

    Maisel, Daniela; Birzele, Fabian; Voss, Edgar; Nopora, Adam; Bader, Sabine; Friess, Thomas; Goller, Bernhard; Laifenfeld, Daphna; Weigand, Stefan; Runza, Valeria

    2016-01-01

    CD44, a transmembrane receptor reported to be involved in various cellular functions, is overexpressed in several cancer types and supposed to be involved in the initiation, progression and prognosis of these cancers. Since the sequence of events following the blockage of the CD44-HA interaction has not yet been studied in detail, we profiled xenograft tumors by RNA Sequencing to elucidate the mode of action of the anti-CD44 antibody RG7356. Analysis of tumor and host gene-expression profiles led us to the hypothesis that treatment with RG7356 antibody leads to an activation of the immune system. Using cytokine measurements we further show that this activation involves the secretion of chemo-attractants necessary for the recruitment of immune cells (i.e. macrophages) to the tumor site. We finally provide evidence for antibody-dependent cellular phagocytosis (ADCP) of the malignant cells by macrophages. PMID:27463372

  16. Targeting Tumor Cells with Anti-CD44 Antibody Triggers Macrophage-Mediated Immune Modulatory Effects in a Cancer Xenograft Model.

    Directory of Open Access Journals (Sweden)

    Daniela Maisel

    Full Text Available CD44, a transmembrane receptor reported to be involved in various cellular functions, is overexpressed in several cancer types and supposed to be involved in the initiation, progression and prognosis of these cancers. Since the sequence of events following the blockage of the CD44-HA interaction has not yet been studied in detail, we profiled xenograft tumors by RNA Sequencing to elucidate the mode of action of the anti-CD44 antibody RG7356. Analysis of tumor and host gene-expression profiles led us to the hypothesis that treatment with RG7356 antibody leads to an activation of the immune system. Using cytokine measurements we further show that this activation involves the secretion of chemo-attractants necessary for the recruitment of immune cells (i.e. macrophages to the tumor site. We finally provide evidence for antibody-dependent cellular phagocytosis (ADCP of the malignant cells by macrophages.

  17. Recovery of valuable chlorosilane intermediates by a novel waste conversion process. Technical report for phase IIIA (final) and phase IIIB (progress)

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, K.E.

    1998-10-01

    From July 1994 through May 1998, direct process residue (DPR) hydrogenolysis has been studied in the laboratory, at a small Pilot Plant, and finally at a larger Pilot Plant within Dow Corning`s Carrollton, Kentucky plant. The system reacts filtered DPR with monomer at high temperature and pressure. The process demonstrates DPR conversion up to 86%. The reaction product contains high concentrations of valuable monomers such as dimethyldichlorosilane and methyldichlorosilane. A larger DPR hydrogenolysis reactor based on these results is being designed for operation in Europe at Dow Corning`s Barry, Wales site.

  18. Analysis and control of the METC fluid bed gasifier. Final report (includes technical progress report for October 1994--January 1995), September 1994--September 1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-09-01

    This document presents a modeling and control study of the Fluid Bed Gasification (FBG) unit at the Morgantown Energy Technology Center (METC). The work is performed under contract no. DE-FG21-94MC31384. The purpose of this study is to generate a simple FBG model from process data, and then use the model to suggest an improved control scheme which will improve operation of the gasifier. The work first developes a simple linear model of the gasifier, then suggests an improved gasifier pressure and MGCR control configuration, and finally suggests the use of a multivariable control strategy for the gasifier.

  19. Heavy chain only antibodies

    DEFF Research Database (Denmark)

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

    2013-01-01

    Unlike conventional antibodies, heavy chain only antibodies derived from camel contain a single variable domain (VHH) and two constant domains (CH2 and CH3). Cloned and isolated VHHs possess unique properties that enable them to excel conventional therapeutic antibodies and their smaller antigen-...... for combating HER2+ breast cancer. © 2013 by Tabriz University of Medical Sciences.......Unlike conventional antibodies, heavy chain only antibodies derived from camel contain a single variable domain (VHH) and two constant domains (CH2 and CH3). Cloned and isolated VHHs possess unique properties that enable them to excel conventional therapeutic antibodies and their smaller antigen......-binding fragments in cancer targeting and therapy. VHHs express low immunogenicity, are highly robust and easy to manufacture and have the ability to recognize hidden or uncommon epitopes. We highlight the utility of VHH in design of new molecular, multifunctional particulate and immune cell-based systems...

  20. Engineering antibody therapeutics.

    Science.gov (United States)

    Chiu, Mark L; Gilliland, Gary L

    2016-06-01

    The successful introduction of antibody-based protein therapeutics into the arsenal of treatments for patients has within a few decades fostered intense innovation in the production and engineering of antibodies. Reviewed here are the methods currently used to produce antibodies along with how our knowledge of the structural and functional characterization of immunoglobulins has resulted in the engineering of antibodies to produce protein therapeutics with unique properties, both biological and biophysical, that are leading to novel therapeutic approaches. Antibody engineering includes the introduction of the antibody combining site (variable regions) into a host of architectures including bi and multi-specific formats that further impact the therapeutic properties leading to further advantages and successes in patient treatment. PMID:27525816

  1. γ-Synuclein antibodies have neuroprotective potential on neuroretinal cells via proteins of the mitochondrial apoptosis pathway.

    Directory of Open Access Journals (Sweden)

    Corina Wilding

    Full Text Available The family of synuclein proteins (α, β and γ are related to neurodegenerative disease e.g. Parkinson disease and Morbus Alzheimer. Additionally, a connection between γ-synuclein and glaucoma, a neurodegenerative disease characterized by a progressive loss of retinal ganglion cells, which finally leads to blindness, exists. The reason for the development of glaucoma is still unknown. Recent studies evaluating the participation of immunological components, demonstrate complex changed antibody reactivities in glaucoma patients in comparison to healthy people, showing not only up-regulations (e.g. alpha-fodrin antibody but also down-regulations (e.g. γ-synuclein antibody of antibodies in glaucoma patients. Up-regulated antibodies could be auto-aggressive, but the role of down-regulated antibodies is still unclear. Previous studies show a significant influence of the serum and the antibodies of glaucoma patients on protein expression profiles of neuroretinal cells. The aim of this study was to investigate the effect of γ-synuclein antibody on the viability and reactive oxygen species levels of a neuroretinal cell line (RGC-5 as well as their interaction with cellular proteins. We found a protective effect of γ-synuclein antibody resulting in an increased viability (up to 15% and decreased reactive oxygen species levels (up to -12% of glutamate and oxidative stressed RGC-5. These can be traced back to anti-apoptotic altered protein expressions in the mitochondrial apoptosis pathway indicated by mass spectrometry and validated by microarray analysis such as active caspase 3, bcl-2 associated-x-protein, S100A4, voltage-dependent anion channel, extracellular-signal-regulated-kinase (down-regulated and baculoviral IAP repeat-containing protein 6, phosphorylated extracellular-signal-regulated-kinase (up-regulated. These changed protein expression are triggered by the γ-synuclein antibody internalization of RGC-5 we could see in immunohistochemical

  2. γ-Synuclein antibodies have neuroprotective potential on neuroretinal cells via proteins of the mitochondrial apoptosis pathway.

    Science.gov (United States)

    Wilding, Corina; Bell, Katharina; Beck, Sabine; Funke, Sebastian; Pfeiffer, Norbert; Grus, Franz H

    2014-01-01

    The family of synuclein proteins (α, β and γ) are related to neurodegenerative disease e.g. Parkinson disease and Morbus Alzheimer. Additionally, a connection between γ-synuclein and glaucoma, a neurodegenerative disease characterized by a progressive loss of retinal ganglion cells, which finally leads to blindness, exists. The reason for the development of glaucoma is still unknown. Recent studies evaluating the participation of immunological components, demonstrate complex changed antibody reactivities in glaucoma patients in comparison to healthy people, showing not only up-regulations (e.g. alpha-fodrin antibody) but also down-regulations (e.g. γ-synuclein antibody) of antibodies in glaucoma patients. Up-regulated antibodies could be auto-aggressive, but the role of down-regulated antibodies is still unclear. Previous studies show a significant influence of the serum and the antibodies of glaucoma patients on protein expression profiles of neuroretinal cells. The aim of this study was to investigate the effect of γ-synuclein antibody on the viability and reactive oxygen species levels of a neuroretinal cell line (RGC-5) as well as their interaction with cellular proteins. We found a protective effect of γ-synuclein antibody resulting in an increased viability (up to 15%) and decreased reactive oxygen species levels (up to -12%) of glutamate and oxidative stressed RGC-5. These can be traced back to anti-apoptotic altered protein expressions in the mitochondrial apoptosis pathway indicated by mass spectrometry and validated by microarray analysis such as active caspase 3, bcl-2 associated-x-protein, S100A4, voltage-dependent anion channel, extracellular-signal-regulated-kinase (down-regulated) and baculoviral IAP repeat-containing protein 6, phosphorylated extracellular-signal-regulated-kinase (up-regulated). These changed protein expression are triggered by the γ-synuclein antibody internalization of RGC-5 we could see in immunohistochemical stainings

  3. State-of-the-art technologies for rapid and high-throughput sample preparation and analysis of N-glycans from antibodies.

    Science.gov (United States)

    Aich, Udayanath; Lakbub, Jude; Liu, Aston

    2016-06-01

    Glycosylation is a PTM that occurs during production of many protein-based biologic drugs and can have a profound impact on their biological, clinical, and pharmacological properties. Quality by design, process optimization, and advance in manufacturing technology create a demand for robust, sensitive, and accurate profiling and quantification of antibody glycosylation. Potential drawbacks in antibody glycosylation profiling include the high hands-on time required for sample preparation and several hours for data acquisition and analysis. Rapid and high-throughput (HTP) N-glycan profiling and characterization along with automation for sample preparation and analysis are essential for extensive antibody glycosylation analysis due to the substantial improvement of turnaround time. The first part of this review article will focus on the recent progress in rapid and HTP sample preparation and analysis of antibody glycosylation. Subsequently, the article will cover a brief overview of various separation and mass spectrometric methods for the rapid and HTP analysis of N-glycans in antibodies. Finally, we will discuss the recent developments in process analytical technologies for the screening and quantification of N-glycans in antibodies.

  4. State-of-the-art technologies for rapid and high-throughput sample preparation and analysis of N-glycans from antibodies.

    Science.gov (United States)

    Aich, Udayanath; Lakbub, Jude; Liu, Aston

    2016-06-01

    Glycosylation is a PTM that occurs during production of many protein-based biologic drugs and can have a profound impact on their biological, clinical, and pharmacological properties. Quality by design, process optimization, and advance in manufacturing technology create a demand for robust, sensitive, and accurate profiling and quantification of antibody glycosylation. Potential drawbacks in antibody glycosylation profiling include the high hands-on time required for sample preparation and several hours for data acquisition and analysis. Rapid and high-throughput (HTP) N-glycan profiling and characterization along with automation for sample preparation and analysis are essential for extensive antibody glycosylation analysis due to the substantial improvement of turnaround time. The first part of this review article will focus on the recent progress in rapid and HTP sample preparation and analysis of antibody glycosylation. Subsequently, the article will cover a brief overview of various separation and mass spectrometric methods for the rapid and HTP analysis of N-glycans in antibodies. Finally, we will discuss the recent developments in process analytical technologies for the screening and quantification of N-glycans in antibodies. PMID:26829758

  5. The INNs and outs of antibody nonproprietary names.

    Science.gov (United States)

    Jones, Tim D; Carter, Paul J; Plückthun, Andreas; Vásquez, Max; Holgate, Robert G E; Hötzel, Isidro; Popplewell, Andrew G; Parren, Paul W H I; Enzelberger, Markus; Rademaker, Hendrik J; Clark, Michael R; Lowe, David C; Dahiyat, Bassil I; Smith, Victoria; Lambert, John M; Wu, Herren; Reilly, Mary; Haurum, John S; Dübel, Stefan; Huston, James S; Schirrmann, Thomas; Janssen, Richard A J; Steegmaier, Martin; Gross, Jane A; Bradbury, Andrew R M; Burton, Dennis R; Dimitrov, Dimiter S; Chester, Kerry A; Glennie, Martin J; Davies, Julian; Walker, Adam; Martin, Steve; McCafferty, John; Baker, Matthew P

    2016-01-01

    An important step in drug development is the assignment of an International Nonproprietary Name (INN) by the World Health Organization (WHO) that provides healthcare professionals with a unique and universally available designated name to identify each pharmaceutical substance. Monoclonal antibody INNs comprise a -mab suffix preceded by a substem indicating the antibody type, e.g., chimeric (-xi-), humanized (-zu-), or human (-u-). The WHO publishes INN definitions that specify how new monoclonal antibody therapeutics are categorized and adapts the definitions to new technologies. However, rapid progress in antibody technologies has blurred the boundaries between existing antibody categories and created a burgeoning array of new antibody formats. Thus, revising the INN system for antibodies is akin to aiming for a rapidly moving target. The WHO recently revised INN definitions for antibodies now to be based on amino acid sequence identity. These new definitions, however, are critically flawed as they are ambiguous and go against decades of scientific literature. A key concern is the imposition of an arbitrary threshold for identity against human germline antibody variable region sequences. This leads to inconsistent classification of somatically mutated human antibodies, humanized antibodies as well as antibodies derived from semi-synthetic/synthetic libraries and transgenic animals. Such sequence-based classification implies clear functional distinction between categories (e.g., immunogenicity). However, there is no scientific evidence to support this. Dialog between the WHO INN Expert Group and key stakeholders is needed to develop a new INN system for antibodies and to avoid confusion and miscommunication between researchers and clinicians prescribing antibodies. PMID:26716992

  6. Plasma Science Committee (PLSC) and the Panel on Opportunities in Plasma Science and Technology (OPST). Final technical progress report, 1 June 1993--31 May 1994

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-12-01

    The Plasma Science Committee (PLSC) of the National Research Council (NRC) is charged with monitoring the health of the field of plasma science in the United States. Accordingly, the Committee identifies and examines both broad and specific issues affecting the field. Regular meetings, teleconferences, briefings from agencies and the scientific community, the formation of study panels to prepare reports, and special symposia are among the mechanisms used by the PLSC to meet its charge. This progress report presents a review of PLSC activities from June 1, 1993 to May 31, 1994. The details of prior activities are discussed in earlier reports. This report also includes the status of activities associated with the PLSC study on opportunities in plasma science and technology. During the above period, the PLSC continued to track and participate in, when requested, discussions on the health of the field. Much of the perspective of the PLSC has been presented in its report Research Briefing on Contemporary Problems in Plasma Science. That report not only has served as the basis for briefings to representatives of the federal government and the community-at-large, but also served as the starting point for the Panel on Opportunities in Plasma Science and Technology (OPST) as it began an assessment of the field. The PLSC also continued its follow-up briefings and discussions on the results of the report Plasma Processing of Materials: Scientific and Technological Opportunities (PPPM). As a result of these activities, the Committee is now working with the NRC Committee on Atomic, Molecular, and Optical Sciences (CAMOS) to organize a symposium on database needs in plasma processing of materials.

  7. RBC Antibody Screen

    Science.gov (United States)

    ... the baby is Rh-positive and the mother's antibody status is negative for anti-D, the mother is given additional RhIG. This test also may be used to help diagnose autoimmune-related hemolytic anemia ... when a person produces antibodies against his or her own RBC antigens. This ...

  8. Selection of Recombinant Human Antibodies.

    Science.gov (United States)

    Tomszak, Florian; Weber, Susanne; Zantow, Jonas; Schirrmann, Thomas; Hust, Michael; Frenzel, André

    2016-01-01

    Since the development of therapeutic antibodies the demand of recombinant human antibodies is steadily increasing. Traditionally, therapeutic antibodies were generated by immunization of rat or mice, the generation of hybridoma clones, cloning of the antibody genes and subsequent humanization and engineering of the lead candidates. In the last few years, techniques were developed that use transgenic animals with a human antibody gene repertoire. Here, modern recombinant DNA technologies can be combined with well established immunization and hybridoma technologies to generate already affinity maturated human antibodies. An alternative are in vitro technologies which enabled the generation of fully human antibodies from antibody gene libraries that even exceed the human antibody repertoire. Specific antibodies can be isolated from these libraries in a very short time and therefore reduce the development time of an antibody drug at a very early stage.In this review, we describe different technologies that are currently used for the in vitro and in vivo generation of human antibodies. PMID:27236551

  9. 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

  10. Rational Design of CXCR4 Specific Antibodies with Elongated CDRs

    Science.gov (United States)

    2015-01-01

    The bovine antibody (BLV1H12) which has an ultralong heavy chain complementarity determining region 3 (CDRH3) provides a novel scaffold for antibody engineering. By substituting the extended CDRH3 of BLV1H12 with modified CXCR4 binding peptides that adopt a β-hairpin conformation, we generated antibodies specifically targeting the ligand binding pocket of CXCR4 receptor. These engineered antibodies selectively bind to CXCR4 expressing cells with binding affinities in the low nanomolar range. In addition, they inhibit SDF-1-dependent signal transduction and cell migration in a transwell assay. Finally, we also demonstrate that a similar strategy can be applied to other CDRs and show that a CDRH2-peptide fusion binds CXCR4 with a Kd of 0.9 nM. This work illustrates the versatility of scaffold-based antibody engineering and could greatly expand the antibody functional repertoire in the future. PMID:25041362

  11. Studies of transport pathways of Th, U, rare earths, Ra-228, and Ra-226 from soil to plants and farm animals: Final progress report, 1983-1988

    Energy Technology Data Exchange (ETDEWEB)

    Linsalata, P

    1988-07-01

    This report consists of three parts. Part 1 discusses a field study conducted in an area of enhanced, natural radioactivity to assess the soil to edible vegetable concentration ratios (CR = concentration in dry vegetable/concentration in dry soil) of Th-232, Th-230, Ra-226, Ra-228, and the light rare earth elements (REE's), La, Ce, and Nd. Twenty-eight soil, and approximately 42 vegetable samples consisting of relatively equal numbers of seven varieties, were obtained from 11 farms on the Pocos de Caldas Plateau in the state of Minas Gerais, Brazil. This region is the site of a major natural analogue study to assess the mobilization and retardation processes affecting thorium and the REE's at the Morro do Ferro ore body, and uranium series radionuclides at the Osamu Utsumi open pit uranium mine. Thorium (IV) serves as a chemical analogue for quadrivalent plutonium, the light REE's (III) as chemical analogues for trivalent americium and curium, and uranium (VI) as an analogue for transuranics with stable oxidation states above IV, e.g., Pu(VI). Part 2 includes our final measurement results for naturally occurring light rare earth elements (REE's include La, Ce, Nd, and SM), U-series and Th-series radionuclides in adult farm animal tissues, feeds and soils. Our findings on soil-to-tissue concentration ratios (CR's) and the comparative behavior of these elements in farm animals raised under natural conditions by local farmers are presented. Part 3 summarizes our findings to date on the distribution and mobilization of Th-232, light rare earth elements (LREE), U-238 and Ra-228 in the MF basin. Estimates of first order, present day, mobilization rate constants resulting from ground water solubilization and seepage/stream transport are calculated using revised inventory estimates for the occurrence of these elements in the ore body and annual flux estimates for the transport of these elements away from the ore body. 151 refs., 20 figs., 40 tabs.

  12. Characterization of superconducting and magnetic materials with muon spin rotation and neutron scattering. Progress report, March 1996--August 1997 and final report, June 1988--August 1997

    Energy Technology Data Exchange (ETDEWEB)

    Stronach, C.E.; Noakes, D.R.

    1997-09-01

    This report represents the culmination of over nine years of research activity in the study of superconducting and magnetically ordered materials using the muon spin rotation ({mu}SR) and neutron scattering techniques. Because all the activities that took place up until March 1996 have been covered in previous annual reports, this final report includes only a brief overview of activities prior to that date, and concentrates on the period from March 1996 through August 1997. The primary activity undertaken in this project has been studies of high-temperature superconductors and their close chemical relatives with the {mu}SR technique. These experiments extend from early work done with a relatively primitive muon beam at the AGS of Brookhaven National Laboratory and large polycrystalline samples of the earliest known high-{Tc} materials to studies of very small high-purity single crystals of the best high-{Tc} materials currently available using the highest quality surface muon beams and specially-designed low-background spectrometers at the Tri-University Meson Facility (TRIUMF) in the past three years. During the period since the last annual report five {mu}SR experiments were done at TRIUMF with DOE support. A study of single-crystal high-temperature superconductors was done in July 1996. A study of the quasicrystal materials Gd{sub 8}Mg{sub 42}Zn{sub 50} and Tb{sub 8}Mg{sub 42}Zn{sub 50} was done by D.R. Noakes in collaboration with G.M. Kalvius of the Technical University of Munich and R. Waeppling of Uppsala University during the first week of December 1996. During the second week of December 1996 a study of the cryocrystals CH{sub 4} and CF{sub 4} was done by D.R. Noakes in collaboration with S. Storchak of Moscow State University and J.H. Brewer of the University of British Columbia. A study of high-{Tc} superconductors was done at TRIUMF during the third week of December 1996 by C.E. Stronach and D.R. Noakes.

  13. Adaptive responses to antibody based therapy.

    Science.gov (United States)

    Rodems, Tamara S; Iida, Mari; Brand, Toni M; Pearson, Hannah E; Orbuch, Rachel A; Flanigan, Bailey G; Wheeler, Deric L

    2016-02-01

    Receptor tyrosine kinases (RTKs) represent a large class of protein kinases that span the cellular membrane. There are 58 human RTKs identified which are grouped into 20 distinct families based upon their ligand binding, sequence homology and structure. They are controlled by ligand binding which activates intrinsic tyrosine-kinase activity. This activity leads to the phosphorylation of distinct tyrosines on the cytoplasmic tail, leading to the activation of cell signaling cascades. These signaling cascades ultimately regulate cellular proliferation, apoptosis, migration, survival and homeostasis of the cell. The vast majority of RTKs have been directly tied to the etiology and progression of cancer. Thus, using antibodies to target RTKs as a cancer therapeutic strategy has been intensely pursued. Although antibodies against the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) have shown promise in the clinical arena, the development of both intrinsic and acquired resistance to antibody-based therapies is now well appreciated. In this review we provide an overview of the RTK family, the biology of EGFR and HER2, as well as an in-depth review of the adaptive responses undertaken by cells in response to antibody based therapies directed against these receptors. A greater understanding of these mechanisms and their relevance in human models will lead to molecular insights in overcoming and circumventing resistance to antibody based therapy. PMID:26808665

  14. Progress of anti-CCP antibody in the application of diagnosis of rheumatoid arthritis%抗CCP抗体在类风湿性关节炎诊断中的应用进展

    Institute of Scientific and Technical Information of China (English)

    梁海; 吴久鸿; 向卓; 张学辉

    2014-01-01

    目前类风湿关节炎的诊断检查有炎性标志物(包括血沉和C反应蛋白)检测,免疫复合物和补体检测,关节滑液检测以及自身抗体检测。这些指标经常伴随类风湿关节炎的活动而改变,早期诊断主要依靠的是自身抗体检测。抗环瓜氨酸肽( cyclic citrullinated peptide,CCP)抗体是一种抗角蛋白抗体,在类风湿性关节炎的敏感度和特异度较类风湿因子高。发病一年内,类风湿性关节炎患者大部分血清中可检测到抗CCP抗体的存在,同时抗CCP抗体阳性也可以用来预测严重破坏的类风湿性关节炎。因此,抗CCP抗体对于类风湿性关节炎的早期诊断及预后评估是极有帮助的。本文综述了近年来抗CCP抗体对于诊断类风湿关节炎的应用进展。%Currently the markers for the diagnosis of rheumatoid arthritis include inflammatory makers ( including blood sedimentation and C-reactive protein) , immune complexe and complement detection, detection of joint synovial fluid, and detection of autoantibodies.These indicators change with the activity of arthritis.Early diagnosis relies mainly on detection of autoantibodies. Anti-cyclic citrullinated peptide antibody( anti-CCP) is a kind of anti-keratin antibody, having higher sensitivity and specificity than the rheumatoid factor in diagnosis of rheumatoid arthritis.During the first year of rheumatoid arthritis, the existence of anti-CCP can be detected in the serum of most of these people.Positive anti-CCP can also be used to predict serious damage.Therefore, anti-CCP is extremely helpful in early diagnosis and prognosis assessment of rheumatoid arthritis.In this paper, the recent application of anti-CCP in the diagnosis of rheumatoid arthritis is reviewed.

  15. Current research status of radioimmunotherapy monoclonal antibody drug

    International Nuclear Information System (INIS)

    Radioimmunotherapy (RIT) was one of the most important progresses in the field of cancer therapy over the past 20 years. It has been successfully applied in the treatment of blood system tumors such as NHL. For the utilization of RIT in therapy of solid tumors, however, development of more effective monoclonal antibodies, labeling methods and so on are needed. The current status of radionuclides, monoclonal antibodies and drugs commonly used in the RIT were briefly reviewed. (authors)

  16. HIV Antibody Test

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? HIV Antibody and HIV Antigen (p24) Share this page: Was this page helpful? Also known as: HIV Screening Tests; AIDS Test; AIDS Screen; HIV Serology; ...

  17. Antinuclear antibody panel

    Science.gov (United States)

    ... blood may be due to: Chronic liver disease Collagen vascular disease Drug-induced lupus erythematosus Myositis (inflammatory muscle disease) ... Saunders; 2011:chap 51. Read More Antibody Arthritis Collagen vascular disease Drug-induced lupus erythematosus Liver disease Scleroderma Systemic ...

  18. Anti-cartilage antibody.

    Science.gov (United States)

    Greenbury, C L; Skingle, J

    1979-08-01

    Antibody to cartilage has been demonstrated by indirect immunofluorescence on rat trachea in the serum of about 3% of 1126 patients with rheumatoid arthritis. Titres ranged from 1:20 to 1:640. The antibody was not found in 284 patients with primary or secondary osteoarthritis or in 1825 blood donors, nor, with the exception of two weak reactors, in 1314 paraplegic patients. In most cases the antibody appears to be specific for native type II collagen. Using this as an antigen in a haemagglutination test 94% of anti-cartilage sera were positive, whereas among 100 rheumatoid control sera there were only three weak positives. More than 80% of patients with antibody had some erosion of articular cartilage, but there was no correlation with age, sex, duration of disease, nor any recognisable clinical event or change.

  19. Phosphokinase antibody arrays on dendron-coated surface.

    Directory of Open Access Journals (Sweden)

    Ju-Won Kwak

    Full Text Available Monitoring protein phosphorylation at the cellular level is important to understand the intracellular signaling. Among the phosphoproteomics methods, phosphokinase antibody arrays have emerged as preferred tools to measure well-characterized phosphorylation in the intracellular signaling. Here, we present a dendron-coated phosphokinase antibody array (DPA in which the antibodies are immobilized on a dendron-coated glass slide. Self-assembly of conically shaped dendrons well-controlled in size and structure resulted in precisely controlled lateral spacing between the immobilized phosphosite-specific antibodies, leading to minimized steric hindrance and improved antigen-antibody binding kinetics. These features increased sensitivity, selectivity, and reproducibility in measured amounts of protein phosphorylation. To demonstrate the utility of the DPA, we generated the phosphorylation profiles of brain tissue samples obtained from Alzheimer's disease (AD model mice. The analysis of the profiles revealed signaling pathways deregulated during the course of AD progression.

  20. Antibody tumor penetration

    Science.gov (United States)

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

    2009-01-01

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

  1. Expression of Recombinant Antibodies

    OpenAIRE

    Frenzel, André; Hust, Michael; Schirrmann, Thomas

    2013-01-01

    Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transg...

  2. Antibody informatics for drug discovery

    DEFF Research Database (Denmark)

    Shirai, Hiroki; Prades, Catherine; Vita, Randi;

    2014-01-01

    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...

  3. Engineering antibodies for cancer therapy.

    Science.gov (United States)

    Boder, Eric T; Jiang, Wei

    2011-01-01

    The advent of modern antibody engineering has led to numerous successes in the application of these proteins for cancer therapy in the 13 years since the first Food and Drug Administration approval, which has stimulated active interest in developing more and better drugs based on these molecules. A wide range of tools for discovering and engineering antibodies has been brought to bear on this challenge in the past two decades. Here, we summarize mechanisms of monoclonal antibody therapeutic activity, challenges to effective antibody-based treatment, existing technologies for antibody engineering, and current concepts for engineering new antibody formats and antibody alternatives as next generation biopharmaceuticals for cancer treatment.

  4. Anti-N-methyl-D-aspartate receptor encephalitis with serum anti-thyroid antibodies and IgM antibodies against Epstein-Barr virus viral capsid antigen: a case report and one year follow-up

    Directory of Open Access Journals (Sweden)

    Xu Chun-Ling

    2011-11-01

    Full Text Available Abstract Background Anti-N-methyl-D-aspartate receptor encephalitis is an increasingly common autoimmune disorder mediated by antibodies to certain subunit of the N-methyl-D-aspartate receptor. Recent literatures have described anti-thyroid and infectious serology in this encephalitis but without follow-up. Case presentation A 17-year-old Chinese female patient presented with psychiatric symptoms, memory deficits, behavioral problems and seizures. She then progressed through unresponsiveness, dyskinesias, autonomic instability and central hypoventilation during treatment. Her conventional blood work on admission showed high titers of IgG antibodies to thyroglobulin, thyroid peroxidase and IgM antibodies to Epstein-Barr virus viral capsid antigen. An immature ovarian teratoma was found and removal of the tumor resulted in a full recovery. The final diagnosis of anti-N-methyl-D-aspartate receptor encephalitis was made by the identification of anti-N-methyl-D-aspartate receptor antibodies in her cerebral spinal fluid. Pathology studies of the teratoma revealed N-methyl-D-aspartate receptor subunit 1 positive ectopic immature nervous tissue and Epstein-Barr virus latent infection. She was discharged with symptoms free, but titers of anti-thyroid peroxidase and anti-thyroglobulin antibodies remained elevated. One year after discharge, her serum remained positive for anti-thyroid peroxidase and anti-N-methyl-D-aspartate receptor antibodies, but negative for anti-thyroglobulin antibodies and IgM against Epstein-Barr virus viral capsid antigen. Conclusions Persistent high titers of anti-thyroid peroxidase antibodies from admission to discharge and until one year later in this patient may suggest a propensity to autoimmunity in anti- N-methyl-D-aspartate receptor encephalitis and support the idea that neuronal and thyroid autoimmunities represent a pathogenic spectrum. Enduring anti-N-methyl-D-aspartate receptor antibodies from admission to one year

  5. Ferredoxin-linked chloreplast enzymes. Progress report, August 15, 1990--August 14, 1993

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-01-01

    Progress has clearly been made on all of the goals set forth in the original proposal. Although the monoclonal antibodies raised against FNR turned out no to be useful for mapping the FNR/ferredoxin or FNR/NADP+ interaction domains, good progress has been made on mapping the FNR/ferredoxin interaction domains by an alternative technique, differential chemical modification. Furthermore, the techniques developed for differential chemical modifications of these two proteins - taurine modification of aspartate and glutamate residues and biotin modification of lysine residues - should be useful for mapping the interaction domains of many proteins that associate through electrostatic interactions. Finally, progress has also been made with respect to another ferredoxin-dependent enzyme involved in the earliest steps of plant nitrogen metabolism - nitrite reductase. Questions concerning the subunit composition and heme content of the enzyme have been resolved and evidence demonstrating the involvement of lysine and arginine residues in binding ferredoxin has been obtained for the first time.

  6. Antibody Conjugates: From Heterogeneous Populations to Defined Reagents

    Directory of Open Access Journals (Sweden)

    Patrick Dennler

    2015-08-01

    Full Text Available Monoclonal antibodies (mAbs and their derivatives are currently the fastest growing class of therapeutics. Even if naked antibodies have proven their value as successful biopharmaceuticals, they suffer from some limitations. To overcome suboptimal therapeutic efficacy, immunoglobulins are conjugated with toxic payloads to form antibody drug conjugates (ADCs and with chelating systems bearing therapeutic radioisotopes to form radioimmunoconjugates (RICs. Besides their therapeutic applications, antibody conjugates are also extensively used for many in vitro assays. A broad variety of methods to functionalize antibodies with various payloads are currently available. The decision as to which conjugation method to use strongly depends on the final purpose of the antibody conjugate. Classical conjugation via amino acid residues is still the most common method to produce antibody conjugates and is suitable for most in vitro applications. In recent years, however, it has become evident that antibody conjugates, which are generated via site-specific conjugation techniques, possess distinct advantages with regard to in vivo properties. Here, we give a comprehensive overview on existing and emerging strategies for the production of covalent and non-covalent antibody conjugates.

  7. Innovative conservation housing. Final progress report

    Energy Technology Data Exchange (ETDEWEB)

    Nuttle, D.A.

    1983-01-01

    A new passive solar thermal storage brick was developed and tested. A new insulating curtain concept was developed to assist in passive solar heating and cooling. A steel truss was designed to replace the wood truss in solar attic applications where the wood truss typically suffers some 50% loss of structural strength. Improvements were made of the dry composting toilet and grey water recycling for homes. An algae cultivation system was created for production of food, feed, fertilizer, or biomass as needed for home, farm, or industry. New concepts were explored in the areas of economy shelter, solar hot water heating, home generation of electricity, edible landscapes and other home food production, growing of fiber crops for cottage industry, storage, insulation, solar cooking, and solar refrigeration. (LEW)

  8. ESG-CET Final Progress Title

    Energy Technology Data Exchange (ETDEWEB)

    Don Middleton

    2011-10-06

    Drawing to a close after five years of funding from DOE's ASCR and BER program offices, the SciDAC-2 project called the Earth System Grid (ESG) Center for Enabling Technologies has successfully established a new capability for serving data from distributed centers. The system enables users to access, analyze, and visualize data using a globally federated collection of networks, computers and software. The ESG software - now known as the Earth System Grid Federation (ESGF) - has attracted a broad developer base and has been widely adopted so that it is now being utilized in serving the most comprehensive multi-model climate data sets in the world. The system is used to support international climate model intercomparison activities as well as high profile U.S. DOE, NOAA, NASA, and NSF projects. It currently provides more than 25,000 users access to more than half a petabyte of climate data (from models and from observations) and has enabled over a 1,000 scientific publications.

  9. Electron Donor Acceptor Interactions. Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    None

    2002-08-16

    The Gordon Research Conference (GRC) on Electron Donor Acceptor Interactions was held at Salve Regina University, Newport, Rhode Island, 8/11-16/02. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  10. Studies in genetic discrimination. Final progress report

    Energy Technology Data Exchange (ETDEWEB)

    1994-06-01

    We have screened 1006 respondents in a study of genetic discrimination. Analysis of these responses has produced evidence of the range of institutions engaged in genetic discrimination and demonstrates the impact of this discrimination on the respondents to the study. We have found that both ignorance and policy underlie genetic discrimination and that anti-discrimination laws are being violated.

  11. Chemical Reactions at Surfaces. Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    None

    2003-02-21

    The Gordon Research Conference (GRC) on Chemical Reactions at Surfaces was held at Holiday Inn, Ventura, California, 2/16-21/03. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  12. Water & Aqueous Solutions. Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    None

    2002-08-09

    The Gordon Research Conference (GRC) on Water & Aqueous Solutions was held at Holderness School, New Hampshire, 8/4/02 thru 8/9/02. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  13. Antibody affinity maturation

    DEFF Research Database (Denmark)

    Skjødt, Mette Louise

    linker for yeast surface display of scFv and scFab fragments, we compared a series of different Gly-Ser-based linkers in display and antigen binding proficiency. We show that these formats of the model antibody can accommodate linkers of different lengths and that introduction of alanine or glutamate......-2. Based on the presented data we suggest that affinity maturation of the model antibody proceeds through multiple incremental steps of subtle improvements. We moreover conclude that the best affinity improved candidates are likely to be obtained through optimization of both the antigen...... fragments by in vivo homologous recombination large combinatorial antibody libraries can easily be generated. We have optimized ordered assembly of three CDR fragments into a gapped vector and observed increased transformation efficiency in a yeast strain carrying a deletion of the SGS1 helicase...

  14. New Antibody Conjugates in Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Serengulam V. Govindan

    2010-01-01

    Full Text Available Targeting of radiation, drugs, and protein toxins to cancers selectively with monoclonal antibodies (MAbs has been a topic of considerable interest and an area of continued development. Radioimmunotherapy (RAIT of lymphoma using directly labeled MAbs is of current interest after approval of two radiolabeled anti-CD20 MAbs, as illustrated with the near 100% overall response rate obtained in a recent clinical trial using an investigational radiolabeled anti-CD22 MAb, 90Y-epratuzumab. The advantage of pretargeted RAIT over directly labeled MAbs is continuing to be validated in preclinical models of lymphoma and solid tumors. Importantly, the advantages of combining RAIT with radiation sensitizers, with immunotherapy, or a drug conjugate targeting a different antigen are being studied clinically and preclinically. The area of drug-conjugated antibodies is progressing with encouraging data published for the trastuzumab-DM1 conjugate in a phase I clinical trial in HER2-positive breast cancer. The Dock-and-Lock platform technology has contributed to the design and the evaluation of complex antibody-cytokine and antibody-toxin conjugates. This review describes the advances made in these areas, with illustrations taken from advances made in the authors' institutions.

  15. Antiphospholipid Antibody Syndrome Presenting with Hemichorea

    Directory of Open Access Journals (Sweden)

    Yezenash Ayalew

    2012-01-01

    Full Text Available A 25-year-old Bangladeshi lady presented to neurology with a three-month history of involuntary movements of her right arm, associated with loss of power. There was progression to the right leg, and she subsequently developed episodes of slurred speech and blurred vision. At the time of presentation, she was 12 weeks pregnant and the symptoms were reported to have started at conception. Past medical history was unremarkable apart from one first trimester miscarriage and there was no significant family history suggestive of a hereditary neurological condition. MRI of the head revealed no abnormalities but serology showed positive antinuclear antibodies (ANAs at a titre of 1/400. Further investigations revealed strongly positive anticardiolipin antibodies (>120 and positive lupus anticoagulant antibodies. The patient had a second miscarriage at 19 weeks gestation strengthening the possibility that the chorea was related to antiphospholipid antibody syndrome and she was started on a reducing dose of Prednisolone 40 mg daily and aspirin 300 mg daily. Six months later, she had complete resolution of neurological symptoms. There are several reports of chorea as a feature of antiphospholipid syndrome, but no clear consensus on underlying pathophysiology.

  16. Progressive Finland sees progress with nuclear projects

    International Nuclear Information System (INIS)

    The Finnish Hanhikivi-1 reactor project is firmly on track and a licence has been granted for construction of a final disposal facility for spent nuclear fuel - the first final repository in the world to enter the construction phase. Significant progress has been made with plans for Finland to build its sixth nuclear reactor unit at Hanhikivi. Fennovoima's licensing manager Janne Liuko said the company expects to receive the construction licence for the Generation III+ Hanhikivi-1 plant in late 2017. The application was submitted to the Finnish Ministry of Employment and the Economy in June 2015.

  17. Progressive Finland sees progress with nuclear projects

    Energy Technology Data Exchange (ETDEWEB)

    Dalton, David [NucNet, Brussels (Belgium)

    2016-02-15

    The Finnish Hanhikivi-1 reactor project is firmly on track and a licence has been granted for construction of a final disposal facility for spent nuclear fuel - the first final repository in the world to enter the construction phase. Significant progress has been made with plans for Finland to build its sixth nuclear reactor unit at Hanhikivi. Fennovoima's licensing manager Janne Liuko said the company expects to receive the construction licence for the Generation III+ Hanhikivi-1 plant in late 2017. The application was submitted to the Finnish Ministry of Employment and the Economy in June 2015.

  18. Antithyroglobulin Antibodies and Antimicrosomal Antibodies in Various Thyroid Diseases

    Energy Technology Data Exchange (ETDEWEB)

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

    1979-03-15

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

  19. The use of combinations of monoclonal antibodies in clinical oncology.

    Science.gov (United States)

    Henricks, Linda M; Schellens, Jan H M; Huitema, Alwin D R; Beijnen, Jos H

    2015-12-01

    Treatment with monoclonal antibodies is becoming increasingly important in clinical oncology. These antibodies specifically inhibit signaling pathways in tumor growth and/or induce immunological responses against tumor cells. By combining monoclonal antibodies several pathways may be targeted simultaneously, potentially leading to additive or synergistic effects. Theoretically, antibodies are very suitable for use in combination therapy, because of limited overlapping toxicity and lack of pharmacokinetic interactions. In this article an overview is given of preclinical and clinical data on twenty-five different combinations of antibodies in oncology. Some of these combinations have proven clinical benefit, for example the combination of trastuzumab and pertuzumab in HER2-positive breast cancer, which exemplifies an additive or synergistic effect on antitumor activity in clinical studies and the combination of nivolumab and ipilimumab, which results in significant increases in progression-free and overall survival in patients with advanced melanoma. However, other combinations may lead to unfavorable results, such as bevacizumab with cetuximab or panitumumab in advanced colorectal cancer. These combinations result in shorter progression-free survival and increased toxicity compared to therapy with a single antibody. In summary, the different published studies showed widely varying results, depending on the combination of antibodies, indication and patient population. More preclinical and clinical studies are necessary to unravel the mechanisms behind synergistic or antagonistic effects of combining monoclonal antibodies. Most research on combination therapies is still in an early stage, but it is expected that for several tumor types the use of combination therapy of antibodies will become standard of care in the near future.

  20. Quarterly Technical Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Ayman I. Hawari

    2002-12-30

    This report presents the progress made during the first quarter of phase 2 for the project entitled ''Development and Validation of Thermal Neutron Scattering Laws from Applications and Safety Implications in Generation IV Reactor Designs.'' (B204) THIS IS NOT A FINAL REPORT

  1. Characterization of antibodies against ferret immunoglobulins, cytokines and CD markers

    DEFF Research Database (Denmark)

    Martel, Cyril Jean-Marie; Aasted, Bent

    2009-01-01

    immunoglobulins, we identified and characterized polyclonal antibodies towards ferret IgG, IgM and IgA. We also identified 22 monoclonal antibodies (mAbs) raised mostly against human CD markers which cross-reacted with ferret leukocytes. These antibodies were originally specific against human CD8, CD9, CD14, CD18......, CD25, CD29, CD32, CD44, CD61, CD71, CD79b, CD88, CD104, CD172a and mink CD3. Finally, we identified 4 cross-reacting mAbs with specificities against ferret interferon-gamma, TNF-alpha, interleukin-4 and interleukin-8....

  2. 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...

  3. Prediction of Antibody Epitopes

    DEFF Research Database (Denmark)

    Nielsen, Morten; Marcatili, Paolo

    2015-01-01

    self-proteins. Given the sequence or the structure of a protein of interest, several methods exploit such features to predict the residues that are more likely to be recognized by an immunoglobulin.Here, we present two methods (BepiPred and DiscoTope) to predict linear and discontinuous antibody...

  4. Lupus anticoagulants and antiphospholipid antibodies

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000547.htm Lupus anticoagulants and antiphospholipid antibodies To use the sharing features on this page, please enable JavaScript. Lupus anticoagulants are antibodies against substances in the lining ...

  5. Discovery of functional monoclonal antibodies targeting G-protein-coupled receptors and ion channels.

    Science.gov (United States)

    Wilkinson, Trevor C I

    2016-06-15

    The development of recombinant antibody therapeutics is a significant area of growth in the pharmaceutical industry with almost 50 approved monoclonal antibodies on the market in the US and Europe. Despite this growth, however, certain classes of important molecular targets have remained intractable to therapeutic antibodies due to complexity of the target molecules. These complex target molecules include G-protein-coupled receptors and ion channels which represent a large potential target class for therapeutic intervention with monoclonal antibodies. Although these targets have typically been addressed by small molecule approaches, the exquisite specificity of antibodies provides a significant opportunity to provide selective modulation of these target proteins. Given this opportunity, substantial effort has been applied to address the technical challenges of targeting these complex membrane proteins with monoclonal antibodies. In this review recent progress made in the strategies for discovery of functional monoclonal antibodies for these challenging membrane protein targets is addressed. PMID:27284048

  6. Recombinant antibodies and tumor targeting

    OpenAIRE

    Sheikholvaezin, Ali

    2006-01-01

    Different antibody derived constructs are rapidly advancing as putative tools for treatment of malignant diseases. Antibody engineering has added significant new technologies to modify size, affinities, solubility, stability and biodistribution properties for immunoconjugates. In the present thesis, the aim was to increase our knowledge on how new recombinant antibodies could be tailored to optimize localization to experimental tumors in mice. One hybridoma, producing the monoclonal antibody ...

  7. A Quantitative Method for Comparing the Brightness of Antibody-dye Reagents and Estimating Antibodies Bound per Cell.

    Science.gov (United States)

    Kantor, Aaron B; Moore, Wayne A; Meehan, Stephen; Parks, David R

    2016-01-01

    We present a quantitative method for comparing the brightness of antibody-dye reagents and estimating antibodies bound per cell. The method is based on complementary binding of test and fill reagents to antibody capture microspheres. Several aliquots of antibody capture beads are stained with varying amounts of the test conjugate. The remaining binding sites on the beads are then filled with a second conjugate containing a different fluorophore. Finally, the fluorescence of the test conjugate compared to the fill conjugate is used to measure the relative brightness of the test conjugate. The fundamental assumption of the test-fill method is that if it takes X molecules of one test antibody to lower the fill signal by Y units, it will take the same X molecules of any other test antibody to give the same effect. We apply a quadratic fit to evaluate the test-fill signal relationship across different amounts of test reagent. If the fit is close to linear, we consider the test reagent to be suitable for quantitative evaluation of antibody binding. To calibrate the antibodies bound per bead, a PE conjugate with 1 PE molecule per antibody is used as a test reagent and the fluorescence scale is calibrated with Quantibrite PE beads. When the fluorescence per antibody molecule has been determined for a particular conjugate, that conjugate can be used for measurement of antibodies bound per cell. This provides comparisons of the brightness of different conjugates when conducted on an instrument whose statistical photoelectron (Spe) scales are known. © 2016 by John Wiley & Sons, Inc.

  8. Digital gangrene associated with anticentromere antibodies: a case report

    Directory of Open Access Journals (Sweden)

    Nair Bindu

    2010-06-01

    Full Text Available Abstract Introduction Anticentromere antibodies have been associated with peripheral vascular occlusive disease, most frequently accompanied by sclerodactyly in the context of a connective tissue disorder. We report a case of digital gangrene with no other clinical associations except positive anticentromere antibodies. Case presentation Our patient, a 53-year-old Caucasian woman, non-smoker, presented with progressive pain and blackening of the distal right third finger over the preceding five weeks. No sclerodactyly was evident. She was anticentromere antibody positive at greater than 100 U/mL. Angiography revealed diffuse distal vasculopathy in both upper extremities. Other investigations were unremarkable. Conclusions It is rare for anticentromere antibody-associated digital necrosis to develop without concomitant sclerodactyly. However, this patient's case illustrates the need to consider an autoimmune contribution to the pathogenesis of digital ischemia even in the absence of a recognizable connective tissue disease.

  9. Improved radioimmunotherapy of hematologic malignancies. Progress report, November 1, 1993--October 31, 1994

    Energy Technology Data Exchange (ETDEWEB)

    Press, O.W.

    1994-08-04

    This report summaries progress made during the time interval between November 1, 1993 and October 31, 1994 and briefly describes studies on the metabolism of antibodies targeting B cell antigens, retention of labeled antibodies by human B cell lymphocytes, and tissue distribution of Chloramine T and tyramine cellobiose labeled antibodies in mice harboring a human erythroleukemia tumor transplant.

  10. DNA immunization as a technology platform for monoclonal antibody induction.

    Science.gov (United States)

    Liu, Shuying; Wang, Shixia; Lu, Shan

    2016-01-01

    To combat the threat of many emerging infectious diseases, DNA immunization offers a unique and powerful approach to the production of high-quality monoclonal antibodies (mAbs) against various pathogens. Compared with traditional protein-based immunization approaches, DNA immunization is efficient for testing novel immunogen designs, does not require the production or purification of proteins from a pathogen or the use of recombinant protein technology and is effective at generating mAbs against conformation-sensitive targets. Although significant progress in the use of DNA immunization to generate mAbs has been made over the last two decades, the literature does not contain an updated summary of this experience. The current review provides a comprehensive analysis of the literature, including our own work, describing the use of DNA immunization to produce highly functional mAbs, in particular, those against emerging infectious diseases. Critical factors such as immunogen design, delivery approach, immunization schedule, use of immune modulators and the role of final boost immunization are discussed in detail. PMID:27048742

  11. Progressive cerebral atrophy in neuromyelitis optica.

    Science.gov (United States)

    Warabi, Yoko; Takahashi, Toshiyuki; Isozaki, Eiji

    2015-12-01

    We report two cases of neuromyelitis optica patients with progressive cerebral atrophy. The patients exhibited characteristic clinical features, including elderly onset, secondary progressive tetraparesis and cognitive impairment, abnormally elevated CSF protein and myelin basic protein levels, and extremely highly elevated serum anti-AQP-4 antibody titer. Because neuromyelitis optica pathology cannot switch from an inflammatory phase to the degenerative phase until the terminal phase, neuromyelitis optica rarely appears as a secondary progressive clinical course caused by axonal degeneration. However, severe intrathecal inflammation and massive destruction of neuroglia could cause a secondary progressive clinical course associated with cerebral atrophy in neuromyelitis optica patients.

  12. A monoclonal antibody against leptin.

    Science.gov (United States)

    Mahmoudian, Jafar; Jeddi-Tehrani, Mahmood; Bayat, Ali Ahmad; Mahmoudi, Ahmad Reza; Vojgani, Yasaman; Tavangar, Banafsheh; Hadavi, Reza; Zarei, Saeed

    2012-10-01

    Leptin is an important protein that regulates energy storage and homeostasis in humans and animals. Leptin deficiency results in various abnormalities such as diabetes, obesity, and infertility. Producing a high affinity monoclonal antibody against human leptin provides an important tool to monitor and trace leptin function in different biological fluids. In this study, recombinant human leptin was conjugated to KLH and injected into mice. After immunization, mouse myeloma SP2/0 cells were fused with murine splenocytes followed by selection of antibody-producing hybridoma cells. After screening of different hybridoma colonies by ELISA, a high affinity antibody was selected and purified by affinity chromatography. The affinity constant of the antibody was measured by ELISA. Western blot, immunocytochemistry, and flow cytometry experiments were used to characterize the antibody. The anti-leptin antibody had a high affinity (around 1.13 × 10(-9) M) for its antigen. The saturation of the antibody with leptin (20 moles leptin per 1 mole antibody) in Western blot analysis proved that the antibody had specific binding to its antigen. Immunocytochemistry and flow cytometry on JEG-3 (human placental choriocarcinoma cell) cells revealed that the anti-leptin antibody recognized intracellular leptin. In conclusion, we report here the production and characterization of a murine anti-leptin antibody with high affinity for human leptin. PMID:23098305

  13. Engineering antibodies by yeast display.

    Science.gov (United States)

    Boder, Eric T; Raeeszadeh-Sarmazdeh, Maryam; Price, J Vincent

    2012-10-15

    Since its first application to antibody engineering 15 years ago, yeast display technology has been developed into a highly potent tool for both affinity maturing lead molecules and isolating novel antibodies and antibody-like species. Robust approaches to the creation of diversity, construction of yeast libraries, and library screening or selection have been elaborated, improving the quality of engineered molecules and certainty of success in an antibody engineering campaign and positioning yeast display as one of the premier antibody engineering technologies currently in use. Here, we summarize the history of antibody engineering by yeast surface display, approaches used in its application, and a number of examples highlighting the utility of this method for antibody engineering.

  14. Antiphospholipid Antibody and Antiphospholipid Syndrome

    Institute of Scientific and Technical Information of China (English)

    吴竞生

    2008-01-01

    @@ Antiphospholipid antibodies (APA) APA is a big category for all kinds of negative charge phospholipid or lecithin - a protein complex autoantibodies or the same antibody, through its recognition of antigen (target protein) different, and phospholipids or lecithin - protein complex combination of various rely on the interference Phospholipid clotting and anti-coagulation factor, and promote endothelial cells, platelets, complement activation and play a role. APA including lupus anticoagulant(LA) and anticardiolipin antibody (ACA), In addition, there are anti-β2 glycoprotein-I (β2-GPI) antibody, anti-prothrombin (a- PT) antibody, anti-lysophosphatidic acid antibody and anti-phosphatidylserine antibody, and so on. APA as the main target of phospholipid-binding protein, including β2-GPI, prothrombin, annexin, protein C (PC) and protein S (PS), plasminogen, and so on.

  15. [Biophysical Characterization of Biopharmaceuticals, Including Antibody Drugs].

    Science.gov (United States)

    Uchiyama, Susumu

    2016-01-01

    Biopharmaceuticals, including antibody drugs, are now popular because of their high specificity with low adverse effects, especially in the treatment of cancer and autoimmune diseases. However, because the active pharmaceutical ingredients of biopharmaceuticals are proteins, biophysical characterization of these therapeutic proteins should be required. In this manuscript, methods of chemical and physical characterization of therapeutic proteins are described. In terms of chemical characterization, analysis of chemical modifications of the constituent amino acids is explained. Physical characterization includes higher order structural analysis and assessment of protein aggregates. Quantification methods of aggregates with different sizes, recently encouraged by the U.S. Food and Drug Administration (FDA), are introduced. As for the stability of therapeutic proteins, the importance of chemical and physical stability is explained. Finally, the contribution of colloidal and structural stability to the production of an antibody drug less prone to aggregation is introduced.

  16. 1985. Annual progress report

    International Nuclear Information System (INIS)

    This annual progress report of the CEA Protection and Nuclear Safety Institut outlines a description of the progress made in each sections of the Institut Research activities of the different departments include: reactor safety analysis, fuel cycle facilities analysis; and associated safety research programs (criticality, sites, transport ...), radioecology and environmental radioprotection techniques; data acquisition on radioactive waste storage sites; radiation effects on man, studies on radioprotection techniques; nuclear material security including security of facilities, security of nuclear material transport, and monitoring of nuclear material management; nuclear facility decommissioning; and finally the public information

  17. The antiphospholipid antibody syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Luma HN

    2012-10-01

    Full Text Available Henry Namme Luma,1,2 Marie-Solange Doualla,1,2 Elvis Temfack,1 Servais Albert Fiacre Eloumou Bagnaka,1 Emmanuella Wankie Mankaa,3 Dobgima Fofung41Department of Internal Medicine, Douala General Hospital, Douala, Cameroon; 2Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon; 3Department of Radiology, Douala General Hospital Douala, Cameroon; 4Department of Abdominal Surgery, Daniel Muna Memorial Clinic, Douala, CameroonAbstract: Antiphospholipid antibody syndrome is defined by the presence of thromboembolic complications and/or pregnancy morbidity in the presence of persistently increased titers of antiphospholipid antibodies. Its clinical presentation can be diverse and any organ can be involved, with a current impact in most surgical and medical specialties. The authors present the case of a 43-year-old man who, over a 13-year period of follow-up, presented with thrombosis of the mesenteric vein, inferior vena cava, and axillary and subclavian veins in a setting where diagnostic and therapeutic options are limited and costly. Through this case report, the authors aim to describe the evolution of this complex pathology, which to date has not been described in the authors' milieu – probably because of its challenging diagnosis and the limited treatment options available. The authors conclude that clinicians need to have a high index of suspicion of APS in patients who present with a thrombotic episode – clinicians should investigate for the presence of antiphospholipid antibodies, as early diagnosis may influence the course of the disease. Furthermore, resources for the detection of antiphospholipid antibodies should be made readily available in resource-limited settings. Finally, patient education on the importance of drug compliance, periodic monitoring, and prevention of thrombosis is indispensable, especially as mortality could be associated with the effects of vascular thrombosis and/or the effects

  18. Progress Report

    DEFF Research Database (Denmark)

    Duer, Karsten

    1999-01-01

    Progress report describing the work carried out by the Danish participant in the ALTSET project in the period January 1999 to July 1999.......Progress report describing the work carried out by the Danish participant in the ALTSET project in the period January 1999 to July 1999....

  19. Challenges in Antibody Development against Tn and Sialyl-Tn Antigens

    Directory of Open Access Journals (Sweden)

    Liliana R. Loureiro

    2015-08-01

    Full Text Available The carbohydrate antigens Tn and sialyl-Tn (STn are expressed in most carcinomas and usually absent in healthy tissues. These antigens have been correlated with cancer progression and poor prognosis, and associated with immunosuppressive microenvironment. Presently they are used in clinical trials as therapeutic vaccination, but with limited success due to their low immunogenicity. Alternatively, anti-Tn and/or STn antibodies may be used to harness the immune system against tumor cells. Whilst the development of antibodies against these antigens had a boost two decades ago for diagnostic use, so far no such antibody entered into clinical trials. Possible limitations are the low specificity and efficiency of existing antibodies and that novel antibodies are still necessary. The vast array of methodologies available today will allow rapid antibody development and novel formats. Following the advent of hybridoma technology, the immortalization of human B cells became a methodology to obtain human monoclonal antibodies with better specificity. Advances in molecular biology including phage display technology for high throughput screening, transgenic mice and more recently molecularly engineered antibodies enhanced the field of antibody production. The development of novel antibodies against Tn and STn taking advantage of innovative technologies and engineering techniques may result in innovative therapeutic antibodies for cancer treatment.

  20. Challenges in Antibody Development against Tn and Sialyl-Tn Antigens

    Science.gov (United States)

    Loureiro, Liliana R.; Carrascal, Mylène A.; Barbas, Ana; Ramalho, José S.; Novo, Carlos; Delannoy, Philippe; Videira, Paula A.

    2015-01-01

    The carbohydrate antigens Tn and sialyl-Tn (STn) are expressed in most carcinomas and usually absent in healthy tissues. These antigens have been correlated with cancer progression and poor prognosis, and associated with immunosuppressive microenvironment. Presently they are used in clinical trials as therapeutic vaccination, but with limited success due to their low immunogenicity. Alternatively, anti-Tn and/or STn antibodies may be used to harness the immune system against tumor cells. Whilst the development of antibodies against these antigens had a boost two decades ago for diagnostic use, so far no such antibody entered into clinical trials. Possible limitations are the low specificity and efficiency of existing antibodies and that novel antibodies are still necessary. The vast array of methodologies available today will allow rapid antibody development and novel formats. Following the advent of hybridoma technology, the immortalization of human B cells became a methodology to obtain human monoclonal antibodies with better specificity. Advances in molecular biology including phage display technology for high throughput screening, transgenic mice and more recently molecularly engineered antibodies enhanced the field of antibody production. The development of novel antibodies against Tn and STn taking advantage of innovative technologies and engineering techniques may result in innovative therapeutic antibodies for cancer treatment. PMID:26270678

  1. [Continuous perfusion culture hybridoma cells for production of monoclonal antibody].

    Science.gov (United States)

    Mi, Li; Li, Ling; Feng, Qiang; Yu, Xiao-Ling; Chen, Zhi-Nan

    2002-05-01

    Hybridoma cells were cultured by continuous perfusion in Fibra-Cel of 5L packed-bed bioreactor for 22 days in low serum or serum-free media. The corresponded amino acids were fed and serum concentration was decreased by analyzing glucose concentration, oxygen uptake rate, secretary antibody amount and amino acids concentration in culture supernatant. Comparing with continuous perfusion culture that amino acids were not fed, antibody amount of production was increased about 2-3 times. The inoculated cell density was 2.5 x 10(5) cells/mL, while the final cell density was 8.79 x 10(8) cells/mL. Antibody production was reached 295 mg/L/d at average level, and the highest level was reached 532 mg/L/d. These results provided a primary mode of enlarge culture for monoclonal antibody industralization. PMID:12192875

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

    DEFF Research Database (Denmark)

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

    1998-01-01

    We have previously reported that slowly progressing HIV infection (SPI) was associated with the presence of contemporaneous autologous neutralizing antibodies. In contrast, a group of individuals with more rapidly progressing infection (RPI) generally lacked these antibodies. To understand...... the importance of autologous neutralizing antibodies in SPI more fully, we have now conducted a prospective study taking consecutive blood samples from the individuals with SPI (8 patients) and RPI (10 patients). Blood sampling in the group with SPI was done 110 and 123 months after the estimated seroconversion...... mean titer [GMT] 8.7 versus 1.6 in SPI and RPI, respectively; p = 0.0048). However, not all individuals with SPI possessed autologous neutralizing antibodies, indicating that other factors may be decisive for SPI. Furthermore, neutralizing antibody titers did not increase from early to late serum...

  3. 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.

  4. VIRAL ANTIBODIES IN PRESCHOOL CHILDREN

    Directory of Open Access Journals (Sweden)

    S. Saidi

    1974-08-01

    Full Text Available One hundred sera from children 1 - 6 years of age, representative of a large serum collection, were tested for the prevalence of antibodies against different viruses. Hemagglutination-inhibition (HI antibodies were found in 68% for measles; 61 % for rubella; 75'% for influenza A2/Hong Kong/68, 16% for influenza B/Md./59, 0% for group A arboviruses, 10% for group B arboviruses, 3% for phlebotomus fever group and 4% for Congo-Crimean hemorrhagic fever (C-CHF group of arboviruses Poliomyelitis-neutralizing antibodies for type 1, 2 and 3 were 90%; 85% and 84%~ respectively. Antibody to EH virus was detected in 84% of the sera by immuno-fluorescence. None of the sera were positive for hepatitis-B antigen or antibody by immuno-precipitation test. The prevalence of some viral antibodies found in this survey are compared with results obtained from surveys in other parts of the country.

  5. Metrics for antibody therapeutics development

    OpenAIRE

    Reichert, Janice M

    2010-01-01

    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approv...

  6. Empowered Antibody Therapies - IBC conference.

    Science.gov (United States)

    Herold, Jens

    2010-10-01

    The Empowered Antibody Therapies conference, held in Burlingame, CA, USA, included topics covering new therapeutic developments in the field of multispecific antibodies. This conference report highlights selected presentations on DVD-Igs from Abbott Laboratories, ImmTACs from Immunocore, 'Dock-and-Lock' technology from Immunomedics, the bispecific BiTE antibody blinatumomab from Micromet, and Triomabs from TRION Pharma and Fresenius Biotech. PMID:20878591

  7. Monoclonal antibodies for treating cancer

    International Nuclear Information System (INIS)

    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. Early detection of emphysema progression

    DEFF Research Database (Denmark)

    Gorbunova, Vladlena; Jacobs, Sander S A M; Lo, Pechin;

    2010-01-01

    more sensitive estimates of emphysema progression. The standard CT densitometric score of emphysema is the relative area of voxels below a threshold (RA). The RA score is a global measurement and reflects the overall emphysema progression. In this work, we propose a framework for estimation of local...... emphysema progression from longitudinal chest CT scans. First, images are registered to a common system of coordinates and then local image dissimilarities are computed in corresponding anatomical locations. Finally, the obtained dissimilarity representation is converted into a single emphysema progression...... score. We applied the proposed algorithm on 27 patients with severe emphysema with CT scans acquired five time points, at baseline, after 3, after 12, after 21 and after 24 or 30 months. The results showed consistent emphysema progression with time and the overall progression score correlates...

  9. Antineutrophil cytoplasmic antibodies

    Directory of Open Access Journals (Sweden)

    G.D. Sebastiani

    2011-06-01

    Full Text Available Antineutrophil cytoplasmic antibodies (ANCA are predominantly IgG autoantibodies directed against constituents of primary granules of neutrophils and monocytes’ lysosomes. Although several antigenic targets have been identified, those ANCA directed to proteinase 3 or myeloperoxidase are clinically relevant, whereas the importance of other ANCA remains unknown. Both are strongly associated with small vessel vasculitides, the ANCA-associated vasculitides, which include Wegener’s granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome, and the localised forms of these diseases (eg, pauci-immune necrotising and crescentic glomerulonephritis. ANCA is a useful serological test to assist in diagnosis of small-vessel vasculitides. 85-95% of patients with Wegener’s granulomatosis, microscopic polyangiitis, and pauci-immune necrotising and crescentic glomerulonephritis have serum ANCA. ANCA directed to either proteinase 3 or myeloperoxidase are clinically relevant, yet the relevance of other ANCA remains unknown. Besides their diagnostic potential, ANCA might be valuable in disease monitoring. In addition, data seem to confirm the long-disputed pathogenic role of these antibodies. There is increasing evidence that myeloperoxidase- ANCA are directly involved in the pathogenesis of necrotizing vasculitis. This is less clear for proteinase 3-ANCA, markers for Wegener’s granulomatosis. With respect to proteinase 3-ANCA, complementary proteinase 3, a peptide translated from the antisense DNA strand of proteinase 3 and homologous to several microbial peptides, may be involved in induction of proteinase 3-antineutrophil cytoplasmic autoantibodies.

  10. Progressive Business

    DEFF Research Database (Denmark)

    Christiansen, Christian O.

    2016-01-01

    Guest Post to the Society for U.S. Intellectual History Blog. Brief introduction to the book Progressive Business: An Intellectual History of the Role of Business in American Society, Oxford U.P., 2015.......Guest Post to the Society for U.S. Intellectual History Blog. Brief introduction to the book Progressive Business: An Intellectual History of the Role of Business in American Society, Oxford U.P., 2015....

  11. Dynamics of specific anti-Mycobacterium avium subsp. paratuberculosis antibody response through age

    DEFF Research Database (Denmark)

    Nielsen, Søren Saxmose; Toft, Nils; Okura, Hisako

    2013-01-01

    G antibodies on their final test-record were used to estimate age-specific sensitivities (Se). These cows were the infected ones considered to develop disease in a population with a representative age-distribution and were defined as cases. The specificity (Sp) of the test was estimated based on test......-results from 166,905 cows, which had no MAP IgG antibodies in their final four test-records. The Sp, age-specific Se and maximum Se were used to estimate the probability of having HI at a given age resulting in the proportion of infected cows with HI at a given age. For cows 2 years of age, the proportion of...... detectable cases was 0.33, while it was 0.94 for cows 5 years of age. Thus, there was a significant shift in the tip of the iceberg with aging. This study provided a model for estimating the proportion of latent chronic infections that would progress to disease, and the results can be used to model infection...

  12. Donor-specific antibodies accelerate arteriosclerosis after kidney transplantation.

    Science.gov (United States)

    Hill, Gary S; Nochy, Dominique; Bruneval, Patrick; Duong van Huyen, J P; Glotz, Denis; Suberbielle, Caroline; Zuber, Julien; Anglicheau, Dany; Empana, Jean-Philippe; Legendre, Christophe; Loupy, Alexandre

    2011-05-01

    In biopsies of renal allografts, arteriosclerosis is often more severe than expected based on the age of the donor, even without a history of rejection vasculitis. To determine whether preformed donor-specific antibodies (DSAs) may contribute to the severity of arteriosclerosis, we examined protocol biopsies from patients with (n=40) or without (n=59) DSA after excluding those with any evidence of vasculitis. Among DSA-positive patients, arteriosclerosis significantly progressed between month 3 and month 12 after transplant (mean Banff cv score 0.65 ± 0.11 to 1.12 ± 0.10, P=0.014); in contrast, among DSA-negative patients, we did not detect a statistically significant progression during the same timeframe (mean Banff cv score 0.65 ± 0.11 to 0.81 ± 0.10, P=not significant). Available biopsies at later time points supported a rate of progression of arteriosclerosis in DSA-negative patients that was approximately one third that in DSA-positive patients. Accelerated arteriosclerosis was significantly associated with peritubular capillary leukocytic infiltration, glomerulitis, subclinical antibody-mediated rejection, and interstitial inflammation. In conclusion, these data support the hypothesis that donor-specific antibodies dramatically accelerate post-transplant progression of arteriosclerosis.

  13. A multicenter evaluation of a new antibody test kit for lymphatic filariasis employing recombinant Brugia malayi antigen Bm-14

    OpenAIRE

    Weil, Gary J; Curtis, Kurt C.; Fischer, Peter U.; Kimberly Y Won; Lammie, Patrick J; Joseph, Hayley; Melrose, Wayne D; Brattig, Norbert W.

    2010-01-01

    Antibody tests are useful for mapping the distribution of lymphatic filariasis (LF) in countries and regions and for monitoring progress in elimination programs based on mass drug administration (MDA). Prior antibody tests have suffered from poor sensitivity and/or specificity or from a lack of standardization. We conducted a multicenter evaluation of a new commercial ELISA that detects IgG4 antibodies to the recombinant filarial antigen Bm14. Four laboratories tested a shared panel of coded ...

  14. Targeting of Antibodies using Aptamers

    OpenAIRE

    Missailidis, Sotiris

    2003-01-01

    The chapter presents a methodology for the rapid selection of aptamers against antibody targets. It is a detailed account of the various methodological steps that describe the selection of aptamers, including PCR steps, buffers to be used, target immobilisation, partitioning and amplification of aptamers, clonning and sequencing, to results in high affinity and specificity ligands for the chosen target antibody.

  15. 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 peptide...

  16. Pathogenic role of antiphospholipid antibodies

    NARCIS (Netherlands)

    Salmon, J. E.; de Groot, P. G.

    2008-01-01

    The antiphospholipid antibody syndrome (APS) is characterized by recurrent arterial and venous thrombosis and/or pregnancy in association with antiphospholipid (aPL) antibodies. The pathogenic mechanisms in APS that lead to in vivo injury are incompletely understood. Recent evidence suggests that AP

  17. Competency development in antibody production in cancer cell biology

    Energy Technology Data Exchange (ETDEWEB)

    Park, M.S.

    1998-12-01

    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). The main objective of this project was to develop a rapid recombinant antibody production technology. To achieve the objective, the authors employed (1) production of recombinant antigens that are important for cell cycle regulation and DNA repair, (2) immunization and specific selection of antibody-producing lymphocytes using the flow cytometry and magnetic bead capturing procedure, (3) construction of single chain antibody library, (4) development of recombinant vectors that target, express, and regulate the expression of intracellular antibodies, and (5) specific inhibition of tumor cell growth in tissue culture. The authors have accomplished (1) optimization of a selection procedure to isolate antigen-specific lymphocytes, (2) optimization of the construction of a single-chain antibody library, and (3) development of a new antibody expression vector for intracellular immunization. The future direction of this research is to continue to test the potential use of the intracellular immunization procedure as a tool to study functions of biological molecules and as an immuno-cancer therapy procedure to inhibit the growth of cancer cells.

  18. Metrics for antibody therapeutics development.

    Science.gov (United States)

    Reichert, Janice M

    2010-01-01

    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approved in the United States, were derived from analysis of a dataset of over 600 therapeutic mAbs that entered clinical study sponsored, at least in part, by commercial firms. The results presented provide an overview of the field and context for the evaluation of on-going and prospective mAb development programs. The expansion of therapeutic antibody use through supplemental marketing approvals and the increase in the study of therapeutics derived from alternative antibody formats are discussed. PMID:20930555

  19. Metrics for antibody therapeutics development.

    Science.gov (United States)

    Reichert, Janice M

    2010-01-01

    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approved in the United States, were derived from analysis of a dataset of over 600 therapeutic mAbs that entered clinical study sponsored, at least in part, by commercial firms. The results presented provide an overview of the field and context for the evaluation of on-going and prospective mAb development programs. The expansion of therapeutic antibody use through supplemental marketing approvals and the increase in the study of therapeutics derived from alternative antibody formats are discussed.

  20. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Gurney, Kevin R

    2015-01-12

    This document constitutes the final report under DOE grant DE-FG-08ER64649. The organization of this document is as follows: first, I will review the original scope of the proposed research. Second, I will present the current draft of a paper nearing submission to Nature Climate Change on the initial results of this funded effort. Finally, I will present the last phase of the research under this grant which has supported a Ph.D. student. To that end, I will present the graduate student’s proposed research, a portion of which is completed and reflected in the paper nearing submission. This final work phase will be completed in the next 12 months. This final workphase will likely result in 1-2 additional publications and we consider the results (as exemplified by the current paper) high quality. The continuing results will acknowledge the funding provided by DOE grant DE-FG-08ER64649.

  1. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    DeTar, Carleton [P.I.

    2012-12-10

    This document constitutes the Final Report for award DE-FC02-06ER41446 as required by the Office of Science. It summarizes accomplishments and provides copies of scientific publications with significant contribution from this award.

  2. Interstitial lung disease in clinically amyopathic dermatomyositis with and without anti-MDA-5 antibody: to lump or split?

    OpenAIRE

    Ikeda, Satoshi; Arita, Machiko; Morita, Mitsunori; Ikeo, Satoshi; Ito, Akihiro; Tokioka, Fumiaki; Noyama, Maki; Misaki, Kenta; Notohara, Kenji; Ishida, Tadashi

    2015-01-01

    Background Interstitial lung disease (ILD) associated with clinically amyopathic dermatomyositis (CADM-ILD) is often refractory and rapidly progressive. Although the anti-melanoma differentiation-associated gene 5 (anti-MDA-5) antibody is associated with rapidly progressive ILD (RP-ILD), differences in clinical features and prognosis of anti-MDA-5 antibody-positive and -negative CADM-ILD remain unclear. Methods To clarify the differences in the clinical features and prognosis between anti-MDA...

  3. Identification of a linear epitope recognized by a monoclonal antibody directed to the heterogeneous nucleoriboprotein A2

    DEFF Research Database (Denmark)

    Tronstrøm, Julie; Dragborg, Anette H.; Hansen, Paul Robert;

    2014-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disorder, characterized by progressive joint destruction and disability. Classical autoantibodies of RA are rheumatoid factors and citrulline antibodies. Patients positive for these autoantibodies are usually associated with a progressive disease...... course. A subgroup of RA patients does not express citrulline antibodies, instead are approximately 35% of these anti-citrulline-negative patients reported to express autoantibodies to the heterogeneous nucleoriboprotein A2, a ribonucleoprotein involved in RNA transport and processing also referred...

  4. Serological antibodies in inflammatory bowel disease: a systematic review.

    Science.gov (United States)

    Prideaux, Lani; De Cruz, Peter; Ng, Siew C; Kamm, Michael A

    2012-07-01

    The diagnosis of inflammatory bowel disease (IBD) is traditionally based on a combination of clinical, endoscopic, histological, and radiological criteria. However, further testing is needed in cases of diagnostic uncertainty and in predicting disease course. This systematic review focuses on the potential for 10 serological antibodies to fill these roles: pANCA, ASCA, anti-OmpC, anti-CBir1, anti-I2, ALCA, ACCA, AMCA, anti-L, and anti-C. We discuss their prevalence in IBD and health; their role in disease diagnosis and risk stratification; their stability over time; their presence in unaffected relatives; their association with genetic variants; and differences across ethnic groups. Serological antibodies have some role in primary diagnosis and in differentiating between Crohn's disease and ulcerative colitis. In indeterminate colitis, preoperative measurement of serological antibodies can help to predict the likelihood of complications among patients undergoing pouch surgery. The combined presence and magnitude of a large panel of antibodies appear to be of value in predicting disease progression. There is currently insufficient evidence to recommend the use of antibody testing to predict responses to treatment or surgery in patients with IBD.

  5. Characterization of single chain antibody targets through yeast two hybrid

    Directory of Open Access Journals (Sweden)

    Vielemeyer Ole

    2010-08-01

    Full Text Available Abstract Background Due to their unique ability to bind their targets with high fidelity, antibodies are used widely not only in biomedical research, but also in many clinical applications. Recombinant antibodies, including single chain variable fragments (scFv, are gaining momentum because they allow powerful in vitro selection and manipulation without loss of function. Regardless of the ultimate application or type of antibody used, precise understanding of the interaction between the antibody's binding site and its specific target epitope(s is of great importance. However, such data is frequently difficult to obtain. Results We describe an approach that allows detailed characterization of a given antibody's target(s using the yeast two-hybrid system. Several recombinant scFv were used as bait and screened against highly complex cDNA libraries. Systematic sequencing of all retained clones and statistical analysis allowed efficient ranking of the prey fragments. Multiple alignment of the obtained cDNA fragments provided a selected interacting domain (SID, efficiently narrowing the epitope-containing region. Interactions between antibodies and their respective targets were characterized for several scFv. For AA2 and ROF7, two conformation-specific sensors that exclusively bind the activated forms of the small GTPases Rab6 and Rab1 respectively, only fragments expressing the entire target protein's core region were retained. This strongly suggested interaction with a non-linear epitope. For two other scFv, TA10 and SF9, which recognize the large proteins giantin and non-muscle myosin IIA, respectively, precise antibody-binding regions within the target were defined. Finally, for some antibodies, secondary targets within and across species could be revealed. Conclusions Our method, utilizing the yeast two-hybrid technology and scFv as bait, is a simple yet powerful approach for the detailed characterization of antibody targets. It allows precise

  6. SPECT assay of radiolabeled monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Jaszczak, R.J.

    1992-02-01

    The long-term goal of this research project is to develop methods to improve the utility of single photon emission computed tomography (SPECI) to quantify the biodistribution of monoclonal antibodies (MoAbs) labeled with clinically relevant radionuclides ({sup 123}I, {sup 131}I, and {sup 111}In) and with another radionuclide,{sup 211}At, recently used in therapy. We describe here our progress in developing quantitative SPECT methodology for {sup 111}In and {sup 123}I. We have focused our recent research thrusts on the following aspects of SPECT: (1) The development of improved SPECT hardware, such as improved acquisition geometries. (2) The development of better reconstruction methods that provide accurate compensation for the physical factors that affect SPECT quantification. (3) The application of carefully designed simulations and experiments to validate our hardware and software approaches.

  7. SPECT assay of radiolabeled monoclonal antibodies

    International Nuclear Information System (INIS)

    The long-term goal of this research project is to develop methods to improve the utility of single photon emission computed tomography (SPECI) to quantify the biodistribution of monoclonal antibodies (MoAbs) labeled with clinically relevant radionuclides (123I, 131I, and 111In) and with another radionuclide,211At, recently used in therapy. We describe here our progress in developing quantitative SPECT methodology for 111In and 123I. We have focused our recent research thrusts on the following aspects of SPECT: (1) The development of improved SPECT hardware, such as improved acquisition geometries. (2) The development of better reconstruction methods that provide accurate compensation for the physical factors that affect SPECT quantification. (3) The application of carefully designed simulations and experiments to validate our hardware and software approaches

  8. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Baron, Edward [Univ. of Oklahoma

    2014-04-28

    The progress over the course of the grant period was excellent. We went from 3-D test codes to full 3-D production codes. We studied several SNe Ia. Most of the support has gone for the 3 years of support of OU graduate student Brian Friesen, who is now mature in his fourth year of research. It is unfortunate that there will be no further DOE support to see him through to the completion of his PhD.

  9. Epitope-specific antibody levels in tuberculosis: biomarkers of protection, disease and response to treatment.

    Directory of Open Access Journals (Sweden)

    Graham H Bothamley

    2014-06-01

    Full Text Available Monoclonal antibodies restricted to Mycobacterium tuberculosis can measure epitope-specific antibody levels in a competition assay. Immunodominant epitopes were defined from clinical samples and related to the clinical spectrum of disease. Antibody to the immunodominant epitopes was associated with HLA-DR15. Occupational exposure showed a different response and was consistent with recognition of dormancy related proteins and protection despite exposure to tuberculosis. Studies in leprosy revealed the importance of immune deviation and the relationships between T and B cell epitopes. During treatment, antibody levels increased, epitope spreading occurred, but the affinity constants remained the same after further antigen exposure, suggesting constraints on the process of epitope selection. Epitope-specific antibody levels have a potential role as biomarkers for new vaccines which might prevent the progression of latent to active tuberculosis and as tools to measure treatment effects on subpopulations of tubercle bacilli.

  10. Neutron spectroscopy. Final report

    International Nuclear Information System (INIS)

    The researches carried by the Columbia University Department of Applied Physics and Nuclear Engineering, and its predecessors, in contract initially with the AEC, then with ERDA, and finally with DOE, had as its initial objective the measurement of fission cross sections and energy distributions of the fission fragments, as measured by pulse heights in detectors. These investigations sought to establish relations between the energy distributions and the quantum numbers of the resonances. In addition, some related, together with some unrelated, investigations were conducted. Progress is reported on measurements on the fissile isotopes, capture cross section measurements, theoretical developments, and the NEVIS synchrocyclotron pulsed neutron source

  11. The antineutrophil antibody in uveitis.

    OpenAIRE

    Young, D W

    1991-01-01

    Ninety eight patients with uveitis of various types were tested for the presence of the antineutrophil antibody or ANCA by an indirect immunofluorescence method. This antibody is found in patients with diseases associated with small vessel vasculitis, including Wegener's granulomatosis and microscopic polyarteritis. Eleven true positive cases were found. A positive test was not associated with the anatomical site of the uveitis but was related to the time course of the disease. In particular ...

  12. Functional effects of anticardiolipin antibodies.

    Science.gov (United States)

    Harris, E N; Pierangeli, S S

    1996-10-01

    The 'lupus anticoagulant' phenomenon is the best documented functional effect of antiphospholipid (aPL) antibodies, occurring either by inhibition of the prothrombinase and/or Factor X activation reactions. Understanding the mechanism by which aPL antibodies inhibit phospholipid dependent coagulation reactions may yield important clues about their 'thrombogenic effects' in vivo. We conducted a series of studies to determine the specificity, diversity, and mechanism by which aPL antibodies inhibit phospholipid dependent reactions. Results showed that purified immunoglobulins with lupus anticoagulant and anti-cardiolipin activities were absorbed by negatively charged phospholipids and both activities were recovered from the phospholipid-antibody precipitate. Purified aPL antibodies inhibited the prothrombinase reaction in a plasma free system in which beta 2-glycoprotein 1 (beta 2-GP1) was absent. Affinity purified aPL antibodies had 25-50 times the inhibitory activity of immunoglobulin preparations. The phospholipid binding proteins, beta 2-GPI and placental anticoagulant protein I (PAP I), independently inhibited the prothrombinase reaction, and when these proteins were combined with aPL, inhibition of the prothrombinase reaction was additive. Antibodies of syphilis had no inhibitory effect, partially accounted for by lack of specificity for phosphotidylserine (PS). Although aPL antibodies inhibited the protein C activation reaction, there was no correlation of these activities with inhibition of the prothrombinase reaction. Together, these results show that aPL exert their effects by interaction with negatively charged phospholipids, in particular phosphotidylserine, but lack of correlation between inhibition of the prothrombinase and protein C activation reactions, suggests that the nature of the coagulation protein is also important. PMID:8902763

  13. Final Report

    DEFF Research Database (Denmark)

    Heiselberg, Per; Brohus, Henrik; Nielsen, Peter V.

    This final report for the Hybrid Ventilation Centre at Aalborg University describes the activities and research achievement in the project period from August 2001 to August 2006. The report summarises the work performed and the results achieved with reference to articles and reports published...

  14. Radiolabeled monoclonal antibodies: a review

    International Nuclear Information System (INIS)

    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)

  15. Radioimmunoguided surgery using monoclonal antibody

    International Nuclear Information System (INIS)

    The potential proficiency of radioimmunoguided surgery in the intraoperative detection of tumors was assessed using labeled monoclonal antibody B72.3 in 66 patients with tissue-proved tumor. Monoclonal antibody B72.3 was injected 5 to 42 days preoperatively, and the hand-held gamma-detecting probe was used intraoperatively to detect the presence of tumor. Intraoperative probe counts of less than 20 every 2 seconds, or tumor-to-adjacent normal tissue ratios less than 2:1 were considered negative (system failure). Positive probe counts were detected in 5 of 6 patients with primary colon cancer (83 percent), in 31 of 39 patients with recurrent colon cancer (79 percent), in 4 of 5 patients with gastric cancer (80 percent), in 3 of 8 patients with breast cancer (37.5 percent), and in 4 of 8 patients with ovarian cancer (50 percent) undergoing second-look procedures. Additional patients in each group were scored as borderline positive. Overall, radioimmunoguided surgery using B72.3 identified tumors in 47 patients (71.2 percent), bordered on positive in 6 patients (9.1 percent), and failed to identify tumor in 13 patients (19.7 percent). Improved selection of patients for antigen-positive tumors, the use of higher affinity second-generation antibodies, alternate routes of antibody administration, alternate radionuclides, and more sophisticatedly bioengineered antibodies and antibody combinations should all lead to improvements in radioimmunoguided surgery

  16. 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.

  17. 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.

  18. Recent Progress in Nuclear Astrophysics

    OpenAIRE

    Langanke, K

    1999-01-01

    The manuscript reviews progress achieved in recent years in various aspects of nuclear astrophysics, including stellar nucleosynthesis, nuclear aspects of supernova collapse and explosion, neutrino-induced reactions and their possible role in the supernova mechanism and nucleosynthesis, explosive hydrogen burning in binary systems, and finally the observation of $\\gamma$-rays from supernova remnants.

  19. 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...

  20. Antibody meets the microbeam - or how to find neurofibrillary tangles

    International Nuclear Information System (INIS)

    In biomedical research the distributions of physiologically or pathologically active elements around or in a certain structure (e.g. tangles, plaques or different cell types) are often of great interest. Therefore, μPIXE analyses are applied to yield quantitative and spatially resolved concentration images of the elements of interest. However, the localisation of the structures to be examined is sometimes scarcely practicable or even impossible. This paper proposes a method of localising the areas of interest for μPIXE analysis. The method is based on the application of a suitable antibody tagged with a single elemental marker (e.g. Ni, Co, Cd, Ag or Au). The antibody then binds selectively to the structures of interest. The elemental marker is detectable via μPIXE, thus, showing finally the structure of interest via the bound antibody. The versatility of the antibodies in combination with the easily applied marker facilitates the localisation of a variety of structures in both light microscopy and μPIXE-imaging. The method is demonstrated on several cellular and subcellular structures in the brain. The elemental concentrations of two consecutive slices, one stained with Ni-enhanced antibody, the other unstained control, are compared to show the feasibility of trace elemental analysis for particular elements in spite if immunohistochemical structure identification. It has to be stated that the proposed technique will not work for free diffusing elements (like Na, Cl, K and Ca) whose concentrations can be altered by wet sample preparation

  1. Antibody meets the microbeam - or how to find neurofibrillary tangles

    Energy Technology Data Exchange (ETDEWEB)

    Morawski, Markus [Paul-Flechsig-Institut fuer Hirnforschung, Universitaet Leipzig, Jahnallee 59, 04109 Leipzig (Germany)]. E-mail: morm@medizin.uni-leipzig.de; Reinert, Tilo [Nukleare Festkoerperphysik, Universitaet Leipzig, Linnestr. 5, 04103 Leipzig (Germany); Meinecke, Christoph [Nukleare Festkoerperphysik, Universitaet Leipzig, Linnestr. 5, 04103 Leipzig (Germany); Arendt, Thomas [Paul-Flechsig-Institut fuer Hirnforschung, Universitaet Leipzig, Jahnallee 59, 04109 Leipzig (Germany); Butz, T. [Nukleare Festkoerperphysik, Universitaet Leipzig, Linnestr. 5, 04103 Leipzig (Germany)

    2005-04-01

    In biomedical research the distributions of physiologically or pathologically active elements around or in a certain structure (e.g. tangles, plaques or different cell types) are often of great interest. Therefore, {mu}PIXE analyses are applied to yield quantitative and spatially resolved concentration images of the elements of interest. However, the localisation of the structures to be examined is sometimes scarcely practicable or even impossible. This paper proposes a method of localising the areas of interest for {mu}PIXE analysis. The method is based on the application of a suitable antibody tagged with a single elemental marker (e.g. Ni, Co, Cd, Ag or Au). The antibody then binds selectively to the structures of interest. The elemental marker is detectable via {mu}PIXE, thus, showing finally the structure of interest via the bound antibody. The versatility of the antibodies in combination with the easily applied marker facilitates the localisation of a variety of structures in both light microscopy and {mu}PIXE-imaging. The method is demonstrated on several cellular and subcellular structures in the brain. The elemental concentrations of two consecutive slices, one stained with Ni-enhanced antibody, the other unstained control, are compared to show the feasibility of trace elemental analysis for particular elements in spite if immunohistochemical structure identification. It has to be stated that the proposed technique will not work for free diffusing elements (like Na, Cl, K and Ca) whose concentrations can be altered by wet sample preparation.

  2. Combining somatic mutations present in different in vivo affinity-matured antibodies isolated from immunized Lama glama yields ultra-potent antibody therapeutics.

    Science.gov (United States)

    Klarenbeek, Alex; Blanchetot, Christophe; Schragel, Georg; Sadi, Ava S; Ongenae, Nico; Hemrika, Wieger; Wijdenes, John; Spinelli, Silvia; Desmyter, Aline; Cambillau, Christian; Hultberg, Anna; Kretz-Rommel, Anke; Dreier, Torsten; De Haard, Hans J W; Roovers, Rob C

    2016-04-01

    Highly potent human antibodies are required to therapeutically neutralize cytokines such as interleukin-6 (IL-6) that is involved in many inflammatory diseases and malignancies. Although a number of mutagenesis approaches exist to perform antibody affinity maturation, these may cause antibody instability and production issues. Thus, a robust and easy antibody affinity maturation strategy to increase antibody potency remains highly desirable. By immunizing llama, cloning the 'immune' antibody repertoire and using phage display, we selected a diverse set of IL-6 antagonistic Fabs. Heavy chain shuffling was performed on the Fab with lowest off-rate, resulting in a panel of variants with even lower off-rate. Structural analysis of the Fab:IL-6 complex suggests that the increased affinity was partly due to a serine to tyrosine switch in HCDR2. This translated into neutralizing capacity in an in vivo model of IL-6 induced SAA production. Finally, a novel Fab library was designed, encoding all variations found in the natural repertoire of VH genes identified after heavy chain shuffling. High stringency selections resulted in identification of a Fab with 250-fold increased potency when re-formatted into IgG1. Compared with a heavily engineered anti-IL-6 monoclonal antibody currently in clinical development, this IgG was at least equally potent, showing the engineering process to have had led to a highly potent anti-IL-6 antibody. PMID:26945588

  3. Production of recombinant antibodies using bacteriophages

    OpenAIRE

    Shukra, A. M.; Sridevi, N. V.; Dev Chandran,; Kapil Maithal,

    2014-01-01

    Recombinant antibody fragments such as Fab, scFv, diabodies, triabodies, single domain antibodies and minibodies have recently emerged as potential alternatives to monoclonal antibodies, which can be engineered using phage display technology. These antibodies match the strengths of conventionally produced monoclonal antibodies and offer advantages for the development of immunodiagnostic kits and assays. These fragments not only retain the specificity of the whole monoclonal ...

  4. The constant region affects antigen binding of antibodies to DNA by altering secondary structure.

    Science.gov (United States)

    Xia, Yumin; Janda, Alena; Eryilmaz, Ertan; Casadevall, Arturo; Putterman, Chaim

    2013-11-01

    We previously demonstrated an important role of the constant region in the pathogenicity of anti-DNA antibodies. To determine the mechanisms by which the constant region affects autoantibody binding, a panel of isotype-switch variants (IgG1, IgG2a, IgG2b) was generated from the murine PL9-11 IgG3 autoantibody. The affinity of the PL9-11 antibody panel for histone was measured by surface plasmon resonance (SPR). Tryptophan fluorescence was used to determine wavelength shifts of the antibody panel upon binding to DNA and histone. Finally, circular dichroism spectroscopy was used to measure changes in secondary structure. SPR analysis revealed significant differences in histone binding affinity between members of the PL9-11 panel. The wavelength shifts of tryptophan fluorescence emission were found to be dependent on the antibody isotype, while circular dichroism analysis determined that changes in antibody secondary structure content differed between isotypes upon antigen binding. Thus, the antigen binding affinity is dependent on the particular constant region expressed. Moreover, the effects of antibody binding to antigen were also constant region dependent. Alteration of secondary structures influenced by constant regions may explain differences in fine specificity of anti-DNA antibodies between antibodies with similar variable regions, as well as cross-reactivity of anti-DNA antibodies with non-DNA antigens.

  5. Protective roles of natural IgM antibodies

    Directory of Open Access Journals (Sweden)

    Caroline eGrönwall

    2012-04-01

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

  6. Anti-erythropoietin receptor antibodies in systemic lupus erythematosus patients with anemia.

    Science.gov (United States)

    Luo, X-Y; Yang, M-H; Peng, Ping; Wu, L-J; Liu, Q-S; Chen, L; Tang, Z; Liu, N-T; Zeng, X-F; Liu, Y; Yuan, G-H

    2013-02-01

    Anemia is a common hematologic abnormality in systemic lupus erythematosus (SLE). An inadequate erythropoietin (EPO) response in SLE patients with anemia has been described that may be due to the presence of antibodies to EPO in SLE patients. However, whether anemia in patients with SLE is related to antibodies to EPO receptor (EPOR) has not yet been investigated. We enlisted 169 consecutive patients with SLE and 45 normal individuals to investigate the existence and importance of circulating autoantibodies to EPOR in sera from patients with SLE. In all patients with SLE, the disease activity was evaluated by using the SLE disease activity index SLEDAI. Anti-EPOR antibodies were detected by using an enzyme-linked immunosorbent assay (ELISA). A higher frequency of anti-EPOR antibodies was observed in SLE patients than in healthy controls (18.3% vs 2.2%, p = 0.007). Moreover, anti-EPOR antibodies were detected in 22 of 69 (31.9%) SLE patients with anemia and in only nine of 100 (9.0%, p antibodies exhibited more severe anemia and often presented as microcytic anemia (p = 0.001). Finally, anti-EPOR antibodies seemed more likely to occur in patients with rash (p = 0.008), lower levels of C(3) component (p = 0.01), higher titer of anti-dsDNA antibodies (p antibodies might play a vital role in SLE patients developing anemia because of the higher incidence of antibodies to EPOR found in SLE patients with anemia. Thus, there might be clinical value in detecting anti-EPOR antibodies in SLE patients with anemia. Therefore, the pathologic role of the antibodies in inducing anemia needs to be established in future studies.

  7. Antibodies to watch in 2016.

    Science.gov (United States)

    Reichert, Janice M

    2016-01-01

    The number of novel antibody therapeutics that received first marketing approvals in 2015 met expectations, with 6 (alirocumab (Praluent®), evolocumab (Repatha®), daratumumab (Darzalex®), dinutuximab (Unituxin®), idarucizumab (Praxbind®), mepolizumab (Nucala®)) granted first approvals as of mid-November*. Seven novel antibody therapeutics (begelomab, brodalumab, elotuzumab, ixekizumab, necitumumab, obiltoxaximab, reslizumab) are in regulatory review, and thus a similar number, if not more, are projected to gain first approvals in 2016. Commercial late-stage antibody therapeutics development exceeded expectations by increasing from 39 candidates in Phase 3 studies as of late 2014 to 53 as of late 2015. Of the 53 candidates, transitions to regulatory review by the end of 2016 are projected for 8 (atezolizumab, benralizumab, bimagrumab, durvalumab, inotuzumab ozogamicin, lebrikizumab, ocrelizumab, tremelimumab). Other "antibodies to watch" include 15 candidates (bavituximab, bococizumab, dupilumab, fasinumab, fulranumab, gevokizumab, guselkumab, ibalizumab, LY2951742, onartuzumab, REGN2222, roledumab, romosozumab, sirukumab, Xilonix) undergoing evaluation in Phase 3 studies that have estimated primary completion dates in 2016. As evidenced by the antibody therapeutics discussed in this perspective, the biopharmaceutical industry has a highly active late-stage clinical pipeline that may deliver numerous new products to the global market in the near future. *See Note added in proof for updates through December 31, 2015. PMID:26651519

  8. Antibody response and antibody affinity maturation in cats with experimental proliferative immune complex glomerulonephritis.

    Science.gov (United States)

    Bishop, S A; Bailey, M; Lucke, V M; Stokes, C R

    1992-07-01

    alteration in IgM affinity occurred at a late stage, as serum IgM levels increased, in cats which progressed to develop GN. These findings suggested that an increase in both serum IgG and IgM anti-HSA values, in particular IgM, was associated with the development of a more severe immune complex renal disease in these cats. Although there was no evidence that differences in the average affinity of either the IgG or IgM antibody populations for HSA, were associated with the development of disease, the increase in IgM values was also accompanied by a concomitant alteration in IgM affinity for antigen.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1430350

  9. Expression of anti-SRP19 antibody in muscle tissues from patients with autoimmune necrotizing myopathy.

    Science.gov (United States)

    Wang, Q; Duan, F; Liu, P; Wang, P F; Wang, M X

    2016-01-01

    This study aimed to investigate the role of anti-SRP19 antibody in muscle tissues of patients with autoimmune necrotizing myopathy. Immunohistochemistry staining was used to determine the expression of anti-SRP19 antibodies in muscle tissues of autoimmune necrotizing myopathy patients. Results demonstrated that anti-SRP19 antibody was expressed in 71.4% (20/28) of muscle tissue specimens from patients with autoimmune necrotizing myopathy. Anti-SRP19 antibody expression was mainly localized in cytoplasm of necrotic muscle fibers surrounding the small blood vessels and interstitial cells. There were no significant differences in the age, course of disease, muscle, and creatine kinase levels between patients with positive or negative expression of anti-SRP19 antibodies. The expression levels of anti-SRP19, serum anti-nuclear antibodies, as well as anti-Ro-52, anti- SSA, anti-Sm, and anti-Jo-1 antibodies were not significantly different among groups. This study demonstrates that anti-SRP19 antibody is highly expressed in muscle tissues of patients with autoimmune necrotizing myopathy, and suggests that this protein may be involved in the origin and progression of the disease. PMID:27525944

  10. 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

    Large-scale molecular dynamics (MD) simulations and atomic force microscopy (AFM) in liquid are combined to characterize the adsorption of Immunoglobulin G (IgG) antibodies over a hydrophobic surface modeled with a three-layer graphene slab. We consider explicitly the water solvent, simulating systems with massive sizes (up to 770 000 atoms), for four different adsorption orientations. Protocols based on steered MD to speed up the protein diffusion stage and to enhance the dehydration process are combined with long simulation times (>150 ns) in order to make sure that the final adsorption states correspond to actual stable configurations. Our 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.Large-scale molecular dynamics (MD) simulations and atomic force microscopy (AFM) in liquid are combined to characterize the adsorption of Immunoglobulin G (IgG) antibodies over a hydrophobic surface modeled with a three-layer graphene slab. We consider explicitly the water solvent, simulating systems with massive sizes (up to 770 000 atoms), for four different adsorption orientations. Protocols based on steered MD to speed up the protein diffusion stage and to enhance the dehydration process are combined with long simulation times (>150 ns) in order to make sure that the final adsorption states correspond to actual stable configurations. Our

  11. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Yelton, John Martin [UF; Mitselmakher, Guenakh [UF; Korytov, Andrey [UF; Avery, Paul [UF; Furic, Ivan [UF; Acosta, Darin [UF; Konigsberg, Jacobo [UF; Field, Richard [UF; Matchev, Konstantin [UF; Ramond, Pierre [UF; Thorn, Richard [UF; Sikivie, Pierre [UF; Ray, Heather [UF; Tanner, David [UF

    2013-10-10

    We report on progress in a series of different directions within high energy physics research. 1. Neutrino research in hardware and software on the Minerva and MiniBooNE experiments 2. Experimental particle physics at the hadron colliders, with emphasis on research and development and data analysis on the CMS experiment operating at the CERN LHC. This includes research on the discovery and properties on the Higgs Boson. 3. Educational outreach through the Quarknet program, taking physics research into High School classrooms. 4. Theoretical and Phenomenological High Energy research, covering a broad range of activities ranging from fundamental theoretical issues to areas of immediate phenomenological importance. 5. Experiment searches for the Axion, as part of the ADMX experiment.

  12. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    R Paul Drake

    2004-01-12

    OAK-B135 This is the final report from the project Hydrodynamics by High-Energy-Density Plasma Flow and Hydrodynamics and Radiation Hydrodynamics with Astrophysical Applications. This project supported a group at the University of Michigan in the invention, design, performance, and analysis of experiments using high-energy-density research facilities. The experiments explored compressible nonlinear hydrodynamics, in particular at decelerating interfaces, and the radiation hydrodynamics of strong shock waves. It has application to supernovae, astrophysical jets, shock-cloud interactions, and radiative shock waves.

  13. Measuring progress

    DEFF Research Database (Denmark)

    Wahlberg, Ayo

    2007-01-01

    . In this paper, I argue that a growing focus on frontier technologies in the life sciences in discussions about bio-power today has come at the cost of empirical investigations into how, for example, 'quality of life' came to be a crucial object of bio-power in the 20th century. Just as Foucault outlined......In recent years, sociological examinations of genetics, therapeutic cloning, neuroscience and tissue engineering have suggested that 'life itself' is currently being transformed through technique with profound implications for the ways in which we understand and govern ourselves and others...... in much the same way that mortality rates, life expectancy or morbidity rates can. By analysing the concrete ways in which human progress has been globally measured and taxonomised in the past two centuries or so, I will show how global stratifications of countries according to their states...

  14. Progress report

    International Nuclear Information System (INIS)

    Progress Report, covering the period up to the end of 1979 year, was sent to the IAEA according to the research agreement No. 1971 /CF. This work covered the following fields: preparation and dummy irradiation experiments with a new experimental capsule of ''CHOUCA-M'' type; measurement of temperature fields and design of specimen holders; measurement of neutron energy spectrum in the irradiation place in our experimental reactor of VVR-S type (Nuclear Research Institute) using a set of activation detectors; unification and calibration of the measurement of neutron fluence with the use of Fe, Cu, Mn-Mg and Co-Al monitors; development and improvement of the measuring apparatus and technique for the dynamic testing of pre-cracked specimens with determination of dynamic parameters of fracture mechanics; preparation and manufacture of testing specimens from the Japanese steels - forging, plate and weld metal; preparation of the irradiation capsule for assembling

  15. Epigenetics of the antibody response.

    Science.gov (United States)

    Li, Guideng; Zan, Hong; Xu, Zhenming; Casali, Paolo

    2013-09-01

    Epigenetic marks, such as DNA methylation, histone post-translational modifications and miRNAs, are induced in B cells by the same stimuli that drive the antibody response. They play major roles in regulating somatic hypermutation (SHM), class switch DNA recombination (CSR), and differentiation to plasma cells or long-lived memory B cells. Histone modifications target the CSR and, possibly, SHM machinery to the immunoglobulin locus; they together with DNA methylation and miRNAs modulate the expression of critical elements of that machinery, such as activation-induced cytidine deaminase (AID), as well as factors central to plasma cell differentiation, such as B lymphocyte-induced maturation protein-1 (Blimp-1). These inducible B cell-intrinsic epigenetic marks instruct the maturation of antibody responses. Their dysregulation plays an important role in aberrant antibody responses to foreign antigens, such as those of microbial pathogens, and self-antigens, such as those targeted in autoimmunity, and B cell neoplasia.

  16. Molecular-specific urokinase antibodies

    Science.gov (United States)

    Atassi, M. Zouhair (Inventor); Morrison, Dennis R. (Inventor)

    2009-01-01

    Antibodies have been developed against the different molecular forms of urokinase using synthetic peptides as immunogens. The peptides were synthesized specifically to represent those regions of the urokinase molecules which are exposed in the three-dimensional configuration of the molecule and are uniquely homologous to urokinase. Antibodies are directed against the lysine 158-isoleucine 159 peptide bond which is cleaved during activation from the single-chain (ScuPA) form to the bioactive double chain (54 KDa and 33 KDa) forms of urokinase and against the lysine 135 lysine 136 bond that is cleaved in the process of removing the alpha-chain from the 54 KDa form to produce the 33 KDa form of urokinase. These antibodies enable the direct measurement of the different molecular forms of urokinase from small samples of conditioned medium harvested from cell cultures.

  17. Tabhu: tools for antibody humanization

    DEFF Research Database (Denmark)

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

    2015-01-01

    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......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...

  18. Autologous antibodies that bind neuroblastoma cells.

    Science.gov (United States)

    Sun, Yujing; Sholler, Giselle S; Shukla, Girja S; Pero, Stephanie C; Carman, Chelsea L; Zhao, Ping; Krag, David N

    2015-11-01

    Antibody therapy of neuroblastoma is promising and our goal is to derive antibodies from patients with neuroblastoma for developing new therapeutic antibodies. The feasibility of using residual bone marrow obtained for clinical indications as a source of tumor cells and a source of antibodies was assessed. From marrow samples, neuroblastoma cells were recovered, grown in cell culture and also implanted into mice to create xenografts. Mononuclear cells from the marrow were used as a source to generate phage display antibody libraries and also hybridomas. Growth of neuroblastoma patient cells was possible both in vitro and as xenografts. Antibodies from the phage libraries and from the monoclonal hybridomas bound autologous neuroblastoma cells with some selectivity. It appears feasible to recover neuroblastoma cells from residual marrow specimens and to generate human antibodies that bind autologous neuroblastoma cells. Expansion of this approach is underway to collect more specimens, optimize methods to generate antibodies, and to evaluate the bioactivity of neuroblastoma-binding antibodies.

  19. [A case of chronic myopathy associated with an antibody to signal recognition particle (SRP) following long-term asymptomatic hypercreatinekinasemia].

    Science.gov (United States)

    Itaya, Kazuhiro; Inoue, Manabu; Iwanami, Hiroaki; Oonaka, Youhei; Jimi, Takahiro; Ichikawa, Hiroo

    2015-01-01

    A 65-year-old man first visited our hospital due to hypercreatinekinasemia (hyperCKemia) (669 IU/l) 12 years ago at age 53. At that time, he had normal muscle strength without other neurological deficits, electromyography (EMG) was normal, and a muscle biopsy obtained from the biceps brachii was intact in routine histochemical studies. These findings led to a diagnosis of idiopathic hyperCKemia that lasted for over a decade. At age 65, the patient became aware of muscle weakness and serum CK was elevated to 4,846 IU/l. Neurological examination revealed very mild atrophy in both thighs, proximal muscle weakness in the left upper and right lower limbs without myalgia, grasping pain, joint pain, and skin lesions. A typical myogenic pattern was detected on EMG exclusively in proximal limb muscles, and fat-suppressed MRI showed high intensity signal areas in adductor magnus muscles. The clinical diagnosis was limb-girdle muscular dystrophy, but MRI findings suggestive of an inflammatory process prompted us to perform muscle biopsy at the rectus femoris. The pathology had characteristic features of necrotizing myopathy containing necrotic and regenerating fibers without prominent inflammatory cell infiltration. Serum anti-signal recognition particle (SRP) antibodies were found to be positive and the final diagnosis was anti-SRP antibody myopathy. Muscle weakness progressed slowly despite therapy with oral corticosteroids. Addition of intravenous high-dose immunoglobulin therapy led to an apparent improvement of muscle weakness in parallel with lowering of the serum CK level. In those who were thought to be idiopathic hyperCKemia or hereditary muscle disorders, potential immunotherapy-effective group does exist. We suggest considering such cases including anti-SRP antibody myopathy during diagnosis, and non-invasive MRI study may be useful to differentiate immunotherapy-effective group from hereditary muscle disorders. PMID:25904255

  20. Radioimmunotherapy with engineered antibody fragments

    International Nuclear Information System (INIS)

    Authors have developed and begun evaluating radiometal-chelated (213Bi) engineered antibody fragments as radioimmunotherapy agents that target the HER2/neu (c-erbB-2) antigen. The diabody format was found to have 40-fold greater affinity for HER2/neu and to be associated with significantly greater tumor localization than is achieved with scFv molecule. It is shown that short-lived isotopes like 213Bi would be most effective when used in conjunction with antibodies that targeted diffuse malignancies (leukemia or lymphoma) or when used for very rapid pretargeted radioimmunotherapy application in which the radioisotope is conjugated to a very small ligand

  1. 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.

  2. 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.

  3. 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.

  4. Antibody profiling sensitivity through increased reporter antibody layering

    International Nuclear Information System (INIS)

    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. Production and characterisation of monoclonal antibodies specific for chicken interleukin-2

    OpenAIRE

    Rothwell, L.; Hamblin, A; Kaiser, P

    2001-01-01

    Using genetic immunisation of mice, we produced antibodies against chicken interleukin-2 (ChIL-2), the first produced against a non-mammalian interleukin. After a final injection with a recombinant ChIL-2 protein, two stable hybridoma cell lines were established which secreted monoclonal antibodies (MAbs) against this cytokine. Specific binding of the two MAbs to recombinant ChIL-2 produced by Escherichia coli and COS-7 cells was demonstrated in an indirect ELISA, Western blotting and dot blo...

  6. Diversification of the Primary Antibody Repertoire by AID-Mediated Gene Conversion.

    Science.gov (United States)

    Lanning, Dennis K; Knight, Katherine L

    2015-01-01

    Gene conversion, mediated by activation-induced cytidine deaminase (AID), has been found to contribute to generation of the primary antibody repertoire in several vertebrate species. Generation of the primary antibody repertoire by gene conversion of immunoglobulin (Ig) genes occurs primarily in gut-associated lymphoid tissues (GALT) and is best described in chicken and rabbit. Here, we discuss current knowledge of the mechanism of gene conversion as well as the contribution of the microbiota in promoting gene conversion of Ig genes. Finally, we propose that the antibody diversification strategy used in GALT species, such as chicken and rabbit, is conserved in a subset of human and mouse B cells.

  7. A Model System for Concurrent Detection of Antigen and Antibody Based on Immunological Fluorescent Method

    OpenAIRE

    2015-01-01

    This paper describes a combined antigen/antibody immunoassay implemented in a 96-well plate using fluorescent spectroscopic method. First, goat anti-human IgG was used to capture human IgG (model antigen); goat anti-human IgG (Cy3 or FITC) was used to detect the model antigen; a saturating level of model antigen was then added followed by unlabelled goat anti-human IgG (model antibody); finally, Cy3 labelled rabbit anti-goat IgG was used to detect the model antibody. Two approaches were appli...

  8. Recent progress in ion sources

    International Nuclear Information System (INIS)

    This paper is intended to survey recent developments in ion sources, particularly work reported at the ''Symposium on Ion Sources and the Formation of Ion Beams'' held in Berkeley in October 1974. The approach here will be to subdivide this topic into three main areas; briefly list and discuss notable progress in each; and finally add some additional detail through a few specific, selected examples. The major items of progress discussed include development of large-area plasma surfaces for multiple- aperture ion sources, a significant increase in available negative-ion current densities, and improved general agreement between extraction electrode design and performance. (U.S.)

  9. Early detection of emphysema progression

    DEFF Research Database (Denmark)

    Gorbunova, Vladlena; Jacobs, Sander S A M; Lo, Pechin;

    2010-01-01

    Emphysema is one of the most widespread diseases in subjects with smoking history. The gold standard method for estimating the severity of emphysema is a lung function test, such as forced expiratory volume in first second (FEV1). However, several clinical studies showed that chest CT scans offer...... emphysema progression from longitudinal chest CT scans. First, images are registered to a common system of coordinates and then local image dissimilarities are computed in corresponding anatomical locations. Finally, the obtained dissimilarity representation is converted into a single emphysema progression...

  10. Early Detection of Emphysema Progression

    DEFF Research Database (Denmark)

    Gorbunova, V.; Jacobs, S.S.A.M.; Lo, Pechin Chien Pau;

    2010-01-01

    Emphysema is one of the most widespread diseases in subjects with smoking history. The gold standard method for estimating the severity of emphysema is a lung function test, such as forced expiratory volume in first second (FEV1). However, several clinical studies showed that chest CT scans offer...... emphysema progression from longitudinal chest CT scans. First, images are registered to a common system of coordinates and then local image dissimilarities are computed in corresponding anatomical locations. Finally, the obtained dissimilarity representation is converted into a single emphysema progression...

  11. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    J. Toulouse

    2012-04-05

    The purpose of this project was to better understand the 'Multiscale Dynamics of Relaxor Ferroelectrics'. The output of the project is summarized in the narrative. The results of the work were presented at a number of different conferences and four papers were written, the references to which are also indicated in the report and which have also been uploaded on e-link. The multiscale dynamics of relaxors was clearly identified in the three characteristic temperatures that were identified. In particular, we were the first group to identify an intermediate temperature, T*, at which the correlations between off-center ions in relaxor cross-over from being dynamic to being static and giving rise to the characteristic relaxor behavior in the dielectric constant. Other groups have now confirmed the existence of such an intermediate temperature. We also made and reported two other observations: (1) a coherent interference phenomena (EIT-like effect) near the transition of several relaxors, which provides information on the nature and mechanism of the transition; and (2) in a similar way, inelastic neutron scattering results were interpreted as resonant scattering of acoustic phonons by localized modes in polar nanodomains. In parallel with the neutron scattering work, we also developed a theory of the scattering of phonons by the above localized modes. The theoretical development is very formal at this point and did not allow an easy comparison with the experimental results. This work is in progress.

  12. Productization and Manufacturing Scaling of High-Efficiency Solar Cell and Module Products Based on a Disruptive Low-Cost, Mono-Crystalline Technology: Final Technical Progress Report, April 1, 2009 - December 30, 2010

    Energy Technology Data Exchange (ETDEWEB)

    Fatemi, H.

    2012-07-01

    Final report for PV incubator subcontract with Solexel, Inc. The purpose of this project was to develop Solexel's Unique IP, productize it, and transfer it to manufacturing. Silicon constitutes a significant fraction of the total solar cell cost, resulting in an industry-wide drive to lower silicon usage. Solexel's disruptive Solar cell structure got around these challenges and promised superior light trapping, efficiency and mechanical strength, despite being significantly thinner than commercially available cells. Solexel's successful participation in this incubator project became evident as the company is now moving into commercial production and position itself to be competitive for the next Technology Pathway Partnerships (TPP) funding opportunity.

  13. Implementing Program Integrity from an HBCU Perspective: Progress, Problems, and Prospects. An Analysis of Part H, Program Integrity - TRIAD of the Higher Education Act and the Final Rules and Related Interim Final Regulations Published in the "Federal Register" on April 29, 1994.

    Science.gov (United States)

    Blakely, William A.

    This paper examines the impact and implications for the nation's 104 historically black colleges and universities (HBCUs) of the final regulations published in the April 29, 1994 "Federal Register" and traces both the legislative and regulatory history of Part H of the Higher Education Act provisions. The analysis addresses specific issues,…

  14. A Model System for Concurrent Detection of Antigen and Antibody Based on Immunological Fluorescent Method

    Directory of Open Access Journals (Sweden)

    Yuan-Cheng Cao

    2015-01-01

    Full Text Available This paper describes a combined antigen/antibody immunoassay implemented in a 96-well plate using fluorescent spectroscopic method. First, goat anti-human IgG was used to capture human IgG (model antigen; goat anti-human IgG (Cy3 or FITC was used to detect the model antigen; a saturating level of model antigen was then added followed by unlabelled goat anti-human IgG (model antibody; finally, Cy3 labelled rabbit anti-goat IgG was used to detect the model antibody. Two approaches were applied to the concomitant assay to analyze the feasibility. The first approach applied FITC and Cy3 when both targets were present at the same time, resulting in 50 ng/mL of the antibody detection limit and 10 ng/mL of antigen detection limit in the quantitative measurements of target concentration, taking the consideration of FRET efficiency of 68% between donor and acceptor. The sequential approach tended to lower the signal/noise (S/N ratio and the detection of the model antigen (lower than 1 ng/mL had better sensitivity than the model antibody (lower than 50 ng/mL. This combined antigen/antibody method might be useful for combined detection of antigens and antibodies. It will be helpful to screen for both antigen and antibody particularly in the situations of the multiserotype and high-frequency mutant virus infections.

  15. Monoclonal antibodies:Principles and applications of immmunodiagnosis and immunotherapy for hepatitis C virus

    Institute of Scientific and Technical Information of China (English)

    Ashraf; Tabll; Aymn; T; Abbas; Sherif; El-Kafrawy; Ahmed; Wahid

    2015-01-01

    Hepatitis C virus(HCV) is a major health problem worldwide. Early detection of the infection will help better management of the infected cases. The monoclonal antibodies(m Ab) of mice are predominantly used for the immunodiagnosis of several viral,bacterial,and parasitic antigens. Serological detection of HCV antigens and antibodies provide simple and rapid methods of detection but lack sensitivity specially in the window phase between the infection and antibody development. Human mA b are used in the immunotherapy of several blood malignancies,such as lymphoma and leukemia,as well as for autoimmune diseases. In this review article,we will discuss methods of mouse and human monoclonal antibody production. We will demonstrate the role of mouse mA b in the detection of HCV antigens as rapid and sensitive immunodiagnostic assays for the detection of HCV,which is a major health problem throughout the world,particularly in Egypt. We will discuss the value of HCV-neutralizing antibodies and their roles in the immunotherapy of HCV infections and in HCV vaccine development. We will also discuss the different mechanisms by which the virus escape the effect of neutralizing mA b. Finally,we will discuss available and new trends to produce antibodies,such as egg yolk-based antibodies(Ig Y),production in transgenic plants,and the synthetic antibody mimics approach.

  16. Research progress of galactose - deficient IgA1 antibodies in diagnosis and treatment of IgA nephropathy%异常糖基化IgA1抗体在IgA肾病诊治中的作用研究进展

    Institute of Scientific and Technical Information of China (English)

    张红; 周楠; 沈颖

    2016-01-01

    研究发现,异常糖基化 IgA1抗体是导致 IgA 肾病(IgAN)发病的重要机制之一。该抗体水平与IgAN 患者蛋白尿水平及肾脏病变程度有显著相关性,检测该抗体对 IgAN 的诊断具有指导价值,其敏感性和特异性可分别达到88%~89%及92%~95%。该抗体对评估临床预后具有指导意义,现对其在 IgAN 诊治的作用进行综述,为治疗 IgAN 提供新方向。%In recent years,studies have shown that galactose - deficient IgA1(Gd - IgA1)antibodies are im-portant in the pathogenesis of IgA nephropathy(IgAN). Serum levels of Gd - IgA1 antibodies are associated with levels of proteinuria and renal histological grading. Measuring the antibodies has guidance value in the diagnosis of IgAN,for its sensitivity and specificity can be up to 88% - 89% and 89% - 92% respectively. In addition,the antibodies play an important role in clinical prognosis,and it may provide a new direction for treatment in IgAN. Now,its role in prognosis of IgAN was reviewed.

  17. Duration of Vi antibodies in participants vaccinated with Typhim Vi (Typhoid Vi polysaccharide vaccine) in an area not endemic for typhoid fever.

    Science.gov (United States)

    Froeschle, James E; Decker, Michael D

    2010-02-10

    After a single injection of Typhim Vi (typhoid Vi polysaccharide vaccine), serum antibody concentrations were monitored for 3 years in 37 adults who resided where typhoid fever was not endemic. Anti-Vi antibody concentrations declined progressively during the study, to levels that support the current US recommendation for revaccination every 2 years.

  18. Alternative affinity tools: more attractive than antibodies?

    NARCIS (Netherlands)

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

    2011-01-01

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

  19. Detection of Campylobacter species using monoclonal antibodies

    Science.gov (United States)

    Young, Colin R.; Lee, Alice; Stanker, Larry H.

    1999-01-01

    A panel of species specific monoclonal antibodies were raised to Campylobacter coli, Campylobacter jejuni and Campylobacter lari. The isotypes, and cross-reactivity profiles of each monoclonal antibody against an extensive panel of micro- organisms, were determined.

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

    Science.gov (United States)

    Watanabe, Osamu

    2013-05-01

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

  1. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Webb, Robert C. [Texas A& M University; Kamon, Teruki [Texas A& M University; Toback, David [Texas A& M University; Safonov, Alexei [Texas A& M University; Dutta, Bhaskar [Texas A& M University; Dimitri, Nanopoulos [Texas A& M University; Pope, Christopher [Texas A& M University; White, James [Texas A& M University

    2013-11-18

    Overview The High Energy Physics Group at Texas A&M University is submitting this final report for our grant number DE-FG02-95ER40917. This grant has supported our wide range of research activities for over a decade. The reports contained here summarize the latest work done by our research team. Task A (Collider Physics Program): CMS & CDF Profs. T. Kamon, A. Safonov, and D. Toback co-lead the Texas A&M (TAMU) collider program focusing on CDF and CMS experiments. Task D: Particle Physics Theory Our particle physics theory task is the combined effort of Profs. B. Dutta, D. Nanopoulos, and C. Pope. Task E (Underground Physics): LUX & NEXT Profs. R. Webb and J. White(deceased) lead the Xenon-based underground research program consisting of two main thrusts: the first, participation in the LUX two-phase xenon dark matter search experiment and the second, detector R&D primarily aimed at developing future detectors for underground physics (e.g. NEXT and LZ).

  2. Production and Screening of Monoclonal Peptide Antibodies.

    Science.gov (United States)

    Trier, Nicole Hartwig; Mortensen, Anne; Schiolborg, Annette; Friis, Tina

    2015-01-01

    Hybridoma technology is a remarkable and indispensable tool for generating high-quality monoclonal antibodies. Hybridoma-derived monoclonal antibodies not only serve as powerful research and diagnostic reagents, but have also emerged as the most rapidly expanding class of therapeutic biologicals. In this chapter, an overview of hybridoma technology and the laboratory procedures used routinely for hybridoma production and antibody screening are presented, including characterization of peptide antibodies.

  3. Virus Strain Discrimination Using Recombinant Antibodies

    OpenAIRE

    Boonham, N.; Barker, I.

    2002-01-01

    Most routine testing for plant viruses is currently carried out using monoclonal and polyclonal antibodies. Traditional methods of antibody production however can be time consuming and require the use of expensive cell culture facilities. Recombinant antibody technology however is starting to make an impact in this area, enabling the selection of antibody fragments in a few weeks compared with the many months associated with traditional methods and requires only basic microbiological faciliti...

  4. Sequence and structural analysis of antibodies

    OpenAIRE

    Raghavan, A. K.

    2009-01-01

    The work presented in this thesis focusses on the sequence and structural analysis of antibodies and has fallen into three main areas. First I developed a method to assess how typical an antibody sequence is of the expressed human antibody repertoire. My hypothesis was that the more \\humanlike" an antibody sequence is (in other words how typical it is of the expressed human repertoire), the less likely it is to elicit an immune response when used in vivo in humans. In practi...

  5. Feasibility of Multiplex Quantum Dot Stain Using Primary Antibodies from Four Distinct Host Animals

    Science.gov (United States)

    Tran, Jonathan K.; Hubbard, Elena N.; Stokes, Todd H.; Moffitt, Richard A.; Wang, May D.

    2016-01-01

    We discuss the feasibility of multiplex QD stain for four biomarkers and our progress in finding four suitable biomarkers from four different hosts. There is a demand for using more than three fluorescent probes on a single tissue sample for disease detection to offer a more reliable prediction of disease progression. We developed a protocol for targeting four biomarkers using four primary antibodies from four different animal hosts. We performed primary-secondary antibody binding assays on nitrocellulose paper and stained breast cancer microarray slides with known expression of ER, PR, and HER2. We identified the lack of a standard protocol and the limited supply of primary antibodies from hosts other than rabbit and mouse in the market as key challenges. The results show variable success in both assays, but indicate future potential for this protocol with more development. PMID:23367436

  6. Preparation and Identification of Anti-rabies Virus Monoclonal Antibodies

    Institute of Scientific and Technical Information of China (English)

    Wen-juan Wang; Xiong Li; Li-hua Wang; Hu Shan; Lei Cao; Peng-cheng Yu; Qing Tang; Guo-dong Liang

    2012-01-01

    To provide a foundation for the development of rapid and specific methods for the diagnosis of rabies virus infection,anti-rabies virus monoclonal antibodies were prepared and rabies virus nucleoprotein and human rabies virus vaccine strain (PV strain) were used as immunogens to immunize 6-8 week old female BALB/c mice.Spleen cells and SP2/0 myeloma cells were fused according to conventional methods:the monoclonal cell strains obtained were selected using the indirect immunofluorescence test; this was followed by preparation of monoclonal antibody ascitic fluid; and finally,systematic identification of subclass,specificity and sensitivity was carried out.Two high potency and specific monoclonal antibodies against rabies virus were obtained and named 3B12 and 4A12,with ascitic fluid titers of 1∶8000 and 1∶10000,respectively.Both belonged to the IgG2a subclass.These strains secrete potent,stable and specific anti-rabies virus monoclonal antibodies,which makes them well suited for the development of rabies diagnosis reagents.

  7. 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

    Large-scale molecular dynamics (MD) simulations and atomic force microscopy (AFM) in liquid are combined to characterize the adsorption of Immunoglobulin G (IgG) antibodies over a hydrophobic surface modeled with a three-layer graphene slab. We consider explicitly the water solvent, simulating systems with massive sizes (up to 770 000 atoms), for four different adsorption orientations. Protocols based on steered MD to speed up the protein diffusion stage and to enhance the dehydration process are combined with long simulation times (>150 ns) in order to make sure that the final adsorption states correspond to actual stable configurations. Our 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. PMID:27352029

  8. Production and purification of polyclonal antibody against melatonin hormone

    Directory of Open Access Journals (Sweden)

    Fooladsaz K

    1999-09-01

    Full Text Available Nowadays immunochemical techniques have played a very important and valuable role in quantitative and qualitative assays of liquid compounds of the body. Producing antibody against immunogenes is the first step to make immunochemical kits. In this study production and purification of polyclonal antibody against melatonin has been considered. This hormone which has several important functions in physiological conditions such as migraine, cirrhosis, mammary gland cancer and other diseases, is the most important pineal gland secretion. This gland is a circumventricular organ of brain and according to histological and anatomical studies, it is a high secretory organ, that secretes active biological substances like melatonin, oxytocin, serotonin and ect. In this study, melatonin has been considered as hapten and has become an immunogen by being linked to the bovine serum Albumin. Then, by the immunization of three white New Zeland rabbits that had the booster injections in regular intervals, the antibody titer was detected to be 1/2000, by using checkboard curves, and with the use of melatonin linked to penicillinase as a labeled antigen, the titer was detected 1/200. Finally an antibody with high purification rate has been obtained, which can be used in immunochemical assays like RIA, ELISA, and EIA.

  9. Hepatitis B and A virus antibodies in alcoholic steatosis and cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Aldershvile, J; Henriksen, J;

    1982-01-01

    Sera from 74 alcoholics with cirrhosis and 63 alcoholics with steatosis were tested for antibody to hepatitis B surface antigen, to hepatitis B core antigen, and to hepatitis A virus by radioimmunoassay or enzyme-linked immunosorbent assay. No significant difference between the two groups...... of alcoholics could be found concerning the prevalence of these antibodies. The total group of patients had antibody to hepatitis B surface antigen or hepatitis B core antigen, or both, significantly (p less than 0.001) more often (26%) than sex- and age-matched controls (4%). No significant difference...... suggest that hepatitis B virus does not play a major role in the progression of alcoholic liver disease, but longitudinal studies are needed to solve this problem. The reason for the increased prevalence of antibodies to hepatitis B virus in these patients is unknown....

  10. High Grade Glioma Mimicking Voltage Gated Potassium Channel Complex Associated Antibody Limbic Encephalitis

    Directory of Open Access Journals (Sweden)

    Dilan Athauda

    2014-01-01

    Full Text Available Though raised titres of voltage gated potassium channel (VGKC complex antibodies have been occasionally associated with extracranial tumours, mainly presenting as Morvan's Syndrome or neuromyotonia, they have not yet been reported to be associated with an intracranial malignancy. This is especially important as misdiagnosis of these conditions and delay of the appropriate treatment can have important prognostic implications. We describe a patient with a high grade glioma presenting with clinical, radiological, and serological features consistent with the diagnosis of VGKC antibody associated limbic encephalitis (LE. This is the first association between a primary brain tumour and high titre of VGKC complex antibodies. Clinicoradiological progression despite effective immunosuppressive treatment should prompt clinicians to look for alternative diagnoses. Further studies to elucidate a possible association between VGKC complex and other surface antigen antibodies with primary brain tumours should be carried out.

  11. High grade glioma mimicking voltage gated potassium channel complex associated antibody limbic encephalitis.

    Science.gov (United States)

    Athauda, Dilan; Delamont, R S; Pablo-Fernandez, E De

    2014-01-01

    Though raised titres of voltage gated potassium channel (VGKC) complex antibodies have been occasionally associated with extracranial tumours, mainly presenting as Morvan's Syndrome or neuromyotonia, they have not yet been reported to be associated with an intracranial malignancy. This is especially important as misdiagnosis of these conditions and delay of the appropriate treatment can have important prognostic implications. We describe a patient with a high grade glioma presenting with clinical, radiological, and serological features consistent with the diagnosis of VGKC antibody associated limbic encephalitis (LE). This is the first association between a primary brain tumour and high titre of VGKC complex antibodies. Clinicoradiological progression despite effective immunosuppressive treatment should prompt clinicians to look for alternative diagnoses. Further studies to elucidate a possible association between VGKC complex and other surface antigen antibodies with primary brain tumours should be carried out.

  12. Immunoglobulin G4: an odd antibody

    NARCIS (Netherlands)

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

    2009-01-01

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

  13. Anti-DNA antibodies in SLE

    Energy Technology Data Exchange (ETDEWEB)

    Voss, E.W.

    1988-01-01

    This book contains 8 chapters. Some of the titles are: Anti-DNA Antibodies in SLE: Historical Perspective; Specificity of Anti-DNA Antibodies in Systemic Lupus Erythematosus; Monoclonial Autoimmune Anti-DNA Antibodies; and Structure--Function Analyses of Anti-DNA Autoantibodies.

  14. FINAL REPORT

    Energy Technology Data Exchange (ETDEWEB)

    PETER, GARY F. [UNIVERSITY OF FLORIDA

    2014-07-16

    Excellent progress was made in standardizing three complementary methods: Magnetic resonance imaging, x-ray micro CT, and MALDI imaging linear ion trap mass spectroscopy to image biomass and chemical, anatomical and functional changes that occur during pretreatment and hydrolysis. Magnetic resonance microscopy provides excellent images with as low as 5 uM resolution with hydrated biomass samples. We visualized dramatic changes in signal associated with the hydrolysis of the carbohydrates by strong acids. Quantitative diffusion approaches were used to probe more subtle structural changes in biomass. Diffusion tensor calculations reflect diffusion anisotropy and fractional anisotropy maps clearly show the longer range diffusion within the vessels compared to within the fiber cells. The diffusion is increased along the cell walls of the vessels. Suggesting that further research with NMR imaging should be pursued. X-ray CT provides excellent images at as low as 3.5 uM resolution from dried biomass. Small increases in surface area, and decreases in local density have been quantified in with wood after mild pretreatments; these changes are expected to be underestimates of the hydrated wood, due to the ~12% shrinkage that occurs upon drying untreated wood. MALDI-MS spectra show high ion intensities at most mass to charge ratios in untreated and pretreated woody material. MALDI-MSn is required to improve specificity and reduce background for imaging. MALDI-TOF is not specific enough for carbohydrate identification. Using MALDI-LIT/MSn we can readily identify oligomeric glucans and xylans and their fragmentation patterns as well as those of the glucuronic acid side chains of birch 4-O-methyl glucuronxylan. Imaging of glucan and xylan oligomers show that many contain isobaric ions with different distributions, indicating again that MSn is needed for accurate imaging of lignocellulosic materials. We are now starting to integrate the three imaging methods by using the same set

  15. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Gentile, Thomas R.

    2014-03-14

    We propose to extend the technique of polarized neutron scattering into new domains by continued development and application of polarized 3He spin-filters. These devices are particularly relevant to the Spallation Neutron Source, as the polarizing monochromators historically used at reactor sources will usually not be suitable polarizers, and wide-angle polarization analysis will be essential. With prior support from the Office of Science, we have developed neutron spin-filters based on the large spin dependence of the cross section for neutron capture by 3He, and applied these devices to a small angle neutron scattering spectrometer (SANS), polarized neutron reflectometers, a thermal energy single crystal diffractometer (SCD), and a thermal energy triple-axis instrument. Our developments have been adopted for application on the magnetism reflectometer at the SNS and for the NIST Center for Neutron Research (NCNR) 3He user capability. Results from both these programs are emerging. We have made significant progress in the past grant period on wide-angle polarization analysis. We have also performed several studies relevant to continuous optical pumping, including collaboration on experiments that have revealed neutron beam effects on spin filters that are continuously pumped by spin-exchange optical pumping. We contributed to an experiment on a neutron interferometer, in which the successful results obtained are directly related to both 3He cell technology and high accuracy 3He -based neutron polarimetry. Implementation of wide-angle polarization analysis will continue to be key thrust for our work in this new proposal. We will also focus on continuous optical pumping and the fundamental issues that determine the achievable 3He polarization. This project will be carried out by a collaboration involving scientists at NIST, Indiana University, Hamilton College, and the Univ. of Wisconsin who are experts in 3He polarization techniques, and materials scientists from the

  16. Aerosol delivered radiolabeled antibodies to ectopic lung carcinoma antigens in scintigraphic tumour detection

    International Nuclear Information System (INIS)

    Biologically specific antibodies offer increased specificity of inhalation scintigraphy in pulmonary malignancy at present limited to detection of airways obstruction. Polypeptide ectopic antigens produced by epithelial lung tumours provide a targeting focus for radiolabeled antibodies. Image resolution using the intravenous route is poor due to the small proportion of the dose targeting to the tumor site and ineffective clearance of the background. The inhalation route minimizes non-specific distribution and utilizes mucociliary clearance as a contrast enhancement mechanism. Mucociliary deposition is cleared more effectively than alveolar deposition. Submicronic aerosol droplets produced by airlet nebulisers ensure peripheral airways penetration and deposition. Affinity purified polyclonal goat antibodies against calcitonin labeled with 150 MBq of Tc-99m are delivered to the lungs to produce dynamic images over 24 hours. Pure synthetic human calcitonin ensures production of monospecific antibodies that can be affinity purified. Labeling with Tc-99m by stannous chloride reduction is effected on the solid phase Sepharose beads. An antibody-antigen concentration gradient over a small distance can be provided with radiolabeled antibodies from aerosol deposition. Histologically neoplastic cells are typically separated from the mucous layer by bronchial mucosa and a thin uninvolved lamina. A localised high concentration of labile antigen is present in extra-cellular spaces at the tumour site. A study is progressing to determine if specific antibody-antigen agglutination contributes towards localised impairment of mucociliary clearance at tumour sites creating contrast

  17. Sensitive detection of platelet-specific antibodies with a modified MAIPA using biotinylated antibodies and streptavidin-coated beads.

    Science.gov (United States)

    Mörtberg, Anette; Meinke, Stephan; Berg, Petra; Killie, Mette Kjær; Kjeldsen-Kragh, Jens; Järås, Kerstin; Refsum, Erle; Höglund, Petter; Wikman, Agneta

    2016-07-01

    We have developed a modified monoclonal antibody immobilization of platelet antigens assay (MAIPA) with enhanced sensitivity in detecting antibodies against human platelet antigens (HPA), using biotinylated monoclonal antibodies, streptavidin-coated beads and detection by flow cytometry. The beads-MAIPA gave superior signal-to-noise resolution (>10-fold higher) for detection of anti-HPA-1a and anti-HPA-5b compared with the in-house standard MAIPA. Also, efficient and reproducible detection of anti-HPA-15 (CD109) was shown. The enhanced sensitivity was confirmed using WHO International Reference Reagents for anti-HPA-1a, anti-HPA-3a and anti-HPA-5b, which allowed comparison of detection endpoints with other laboratories. Finally, the beads-MAIPA was validated for quantification of anti-HPA-1a. The lower limit of quantification was 0.4IU/mL for beads-MAIPA, compared to 1IU/mL previously reported for standard MAIPA. Based on improved performance against all HPA-antibodies tested, the beads-MAIPA has replaced the standard MAIPA in our laboratory in diagnostics of conditions due to HPA-immunization, such as fetal and neonatal alloimmune thrombocytopenia (FNAIT). PMID:27059653

  18. Immunosuppression associated with novel chemotherapy agents and monoclonal antibodies.

    Science.gov (United States)

    Morrison, Vicki A

    2014-11-15

    The introduction of novel agents to the therapeutic armamentarium for oncologic, rheumatologic, and neurologic disorders has resulted in major clinical advances. These agents impact immune function, resulting in a discrete spectrum of infectious complications. Purine analogues and alemtuzumab alter cell-mediated immunity, resulting in opportunistic viral/fungal infections. Herpes zoster incidence increases with bortezomib. Hepatitis B reactivation may occur with rituximab. Cases of progressive multifocal leukoencephalopathy have occurred following monoclonal antibody therapy. Tumor necrosis factor-α inhibitor therapy is complicated by tuberculosis reactivation and fungal infections. We summarize the impact of these therapies on pathogenesis and spectrum of infection complicating their usage. PMID:25352632

  19. EDITORIAL: Catalysing progress Catalysing progress

    Science.gov (United States)

    Demming, Anna

    2010-01-01

    Examples of the merits of blue-sky research in the history of science are legion. The invention of the laser, celebrating its 50th anniversary this year, is an excellent example. When it was invented it was considered to be 'a solution waiting for a problem', and yet the level to which it has now infiltrated our day-to-day technological landscape speaks volumes. At the same time it is also true to say that the direction of research is also at times rightly influenced by the needs and concerns of the general public. Over recent years, growing concerns about the environment have had a noticeable effect on research in nanotechnology, motivating work on a range of topics from green nanomaterial synthesis [1] to high-efficiency solar cells [2] and hydrogen storage [3]. The impact of the world's energy consumption on the welfare of the planet is now an enduring and well founded concern. In the face of an instinctive reluctance to curtail habits of comfort and convenience and the appendages of culture and consumerism, research into renewable and more efficient energy sources seem an encouraging approach to alleviating an impending energy crisis. Fuel cells present one alternative to traditional combustion cells that have huge benefits in terms of the efficiency of energy conversion and the limited harmful emissions. In last week's issue of Nanotechnology, Chuan-Jian Zhong and colleagues at the State University of New York at Binghamton in the USA presented an overview of research on nanostructured catalysts in fuel cells [4]. The topical review includes insights into the interactions between nanoparticles and between nanoparticles and their substrate as well as control over the composition and nanostructure of catalysts. The review also serves to highlight how the flourishing of nanotechnology research has heralded great progress in the exploitation of catalysts with nanostructures ingeniously controlled to maximize surface area and optimize energetics for synthesis

  20. EDITORIAL: Catalysing progress Catalysing progress

    Science.gov (United States)

    Demming, Anna

    2010-01-01

    Examples of the merits of blue-sky research in the history of science are legion. The invention of the laser, celebrating its 50th anniversary this year, is an excellent example. When it was invented it was considered to be 'a solution waiting for a problem', and yet the level to which it has now infiltrated our day-to-day technological landscape speaks volumes. At the same time it is also true to say that the direction of research is also at times rightly influenced by the needs and concerns of the general public. Over recent years, growing concerns about the environment have had a noticeable effect on research in nanotechnology, motivating work on a range of topics from green nanomaterial synthesis [1] to high-efficiency solar cells [2] and hydrogen storage [3]. The impact of the world's energy consumption on the welfare of the planet is now an enduring and well founded concern. In the face of an instinctive reluctance to curtail habits of comfort and convenience and the appendages of culture and consumerism, research into renewable and more efficient energy sources seem an encouraging approach to alleviating an impending energy crisis. Fuel cells present one alternative to traditional combustion cells that have huge benefits in terms of the efficiency of energy conversion and the limited harmful emissions. In last week's issue of Nanotechnology, Chuan-Jian Zhong and colleagues at the State University of New York at Binghamton in the USA presented an overview of research on nanostructured catalysts in fuel cells [4]. The topical review includes insights into the interactions between nanoparticles and between nanoparticles and their substrate as well as control over the composition and nanostructure of catalysts. The review also serves to highlight how the flourishing of nanotechnology research has heralded great progress in the exploitation of catalysts with nanostructures ingeniously controlled to maximize surface area and optimize energetics for synthesis

  1. Immunoradiometric assay for the detection of circulating antibodies to murine monoclonal antibodies in humans (HAMA)

    International Nuclear Information System (INIS)

    The increasing clinical use of monoclonal antibodies (MAb) has focussed attention on the importance of the generation of human anti-mouse antibodies (HAMA). HAMA can not only be life threatening but can also be associated with reduced image quality and accelerated MAb clearance in vivo as well as interfere with in vitro MAb based assays. The development of a two step immunoradiometric assay (IRMA) for detecting circulating HAMA is reported. Preliminary results have been generated with specific MAb coated polystyrene wells. The appropriately diluted serum sample is first incubated with the MAb coated wells followed by a wash step and a second incubation with 125I labeled goat anti-human IgG. After a final wash, the wells are assayed for 125I and the results expressed as percent of the input bound. The prototype assay is compared with an existing commercially available ELISA kit using patient sera obtained at various time periods up to 7 months after IV MAb injection for radioimmunoscintigraphy. 18 refs., 2 tabs., 1 fig

  2. The role of antibodies in myasthenia gravis.

    Science.gov (United States)

    De Baets, M; Stassen, M H W

    2002-10-15

    Myasthenia gravis is an autoimmune disease associated with antibodies directed to the postsynaptic acetylcholine receptor. These antibodies reduce the number of receptors. Autoantibodies against AChR and other muscle antigens can be used for the diagnosis of myasthenia gravis and related disorders. The origin and the role of these antibodies in the disease are discussed. Experimental autoimmune myasthenia gravis, an experimental model closely mimicking the disease, has provided answers to many questions about the role of antibodies, complement macrophages and AChR anchor proteins. Genetically modified anti-AChR antibodies may also be used in the future to treat myasthenia. PMID:12220686

  3. Production of Monoclonal Antibody against Human Nestin.

    Science.gov (United States)

    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

    2010-04-01

    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 as ELISA, flow cytometry, immunocytochemistry, and Western blot assays. PMID:23407796

  4. 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...

  5. Monoclonal Antibody Therapies against Anthrax

    OpenAIRE

    Zhaochun Chen; Mahtab Moayeri; Robert Purcell

    2011-01-01

    Anthrax is a highly lethal infectious disease caused by the spore-forming bacterium Bacillus anthracis. It not only causes natural infection in humans but also poses a great threat as an emerging bioterror agent. The lethality of anthrax is primarily attributed to the two major virulence factors: toxins and capsule. An extensive effort has been made to generate therapeutically useful monoclonal antibodies to each of the virulence components: protective antigen (PA), lethal factor (LF) and ede...

  6. Antibody Peptide Based Antifungal Immunotherapy

    OpenAIRE

    Magliani, Walter; Conti, Stefania; Giovati, Laura; Zanello, Pier Paolo; Sperindè, Martina; Ciociola, Tecla; Polonelli, Luciano

    2012-01-01

    Fungal infections still represent relevant human illnesses worldwide and some are accompanied by unacceptably high mortality rates. The limited current availability of effective and safe antifungal agents makes the development of new drugs and approaches of antifungal vaccination/immunotherapy every day more needed. Among them, small antibody(Ab)-derived peptides are arousing great expectations as new potential antifungal agents. In this topic, the search path from the study of the yeast kill...

  7. Search for a final repository. Final repository commission and the public. Questions concerning cooperation and progress of the process at half time of the commission; Endlagersuche. Endlager-Kommission und Oeffentlichkeit(en). Fragen nach Zusammenarbeit und Fortschritten im Prozess zur Halbzeit der Kommission

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Monika C.M. (ed.) [Evangelische Akademie Loccum (Germany). Arbeitsbereich Naturwissenschaften, Oekologie und Umweltpolitik

    2016-08-01

    The volume includes the following contributions: Presumptions and success of public participation. Refusal as legitimate and necessary mean. Experiences form the participation process in Switzerland. Cooperation of the final repository commission and the public. Regional participation: the view of a process attendant in the Swiss procedure. Synergies or friction losses? Who is coordinating the institutions/activities and is bringing them together? Players in the nuclear waste conflict - rights and duties in the frame of the search for waste storage as safe as possible. Transparency and Participation - what is the role of online media in the site search process?.

  8. [Treatments of progressive systemic sclerosis].

    Science.gov (United States)

    Vayssairat, M; Abdoucheli-Baudot, N; Gaitz, J P

    2001-10-01

    Progressive Systemic Sclerosis (PSS) is still an incurable disease but there are treatments for it, and the list of proposed treatments is long. The methodology of trials concerning PSS is complex, due to the low prevalence of the disease and therefore its financial interest for pharmaceutical companies, the lack of simple end points for efficacy, and the large number of clinical expressions with various prognoses. These causes explain why most open studies are fiercely positive, and why controlled studies are so rare. The progress made during the last 10 years concern 1) the diagnosis, which is now made earlier due to capillaroscopy and antibody assays, especially of anticentromere antibodies, 2) better knowledge of the prognosis, due to the classification of PSS into limited and the diffuse forms which have different prognoses, and 3) the recognition of a serious complication of the disease, ie. pulmonary hypertension, which can now be detected by non-invasive methods. All these improvements will also improve the methodology of future trials of drugs for treating PSS. In this ocean of uncertainties, some treatments have a valid background, and 3 visceral locations of PSS can be efficiently treated: renal involvement, with angiotensin-converting enzyme inhibitors, respiratory involvement, with D-penicillamine, and pulmonary hypertension, with prostacyclin derivatives. Corticosteroids are suspected to increase the risk of renal complications. Calcium blockers are considered a useful symptomatic treatment of the associated Raynaud's phenomenon and of the risk of digital necrosis, and may also constitute a treatment of PSS itself. A recent trial conducted by the French Microcirculation Society and its acrosyndrome Study Group considered the effects of an oral derivative of prostacyclin. Beneficial effects were: a reduction of the risk of digital necroses, improved overall wellbeing, less necessity for hospitalizations, fewer giant capillaries, and a dramatic fall in

  9. Application of Monoclonal Antibodies in Veterinary Parasitology

    Directory of Open Access Journals (Sweden)

    Gupta A.

    2011-08-01

    Full Text Available The discovery of hybridoma technology by Kohler and Milstein in 1975, heralded a new era in antibody research. Mouse hybridomas were the first reliable source of monoclonal antibodies. The generation of monoclonal antibodies from species other than rats and mice, has developed slowly over the last 30 years. The advent of antibody engineering and realization of the advantages of non murine antibodies has increased their relevance recently. However, in the area of veterinary parasitology, monoclonal antibodies are just beginning to fulfill the promises inherent in their great specificity for recognizing and selectively binding to antigens. This review describes the recent advances in the application of monoclonal antibodies for immunodiagnosis / prophylaxis and immunotherapy of parasitic diseases. [Vet. World 2011; 4(4.000: 183-188

  10. Low prevalence of antibodies and other plasma factors binding to CC chemokines and IL-2 in HIV-positive patients

    DEFF Research Database (Denmark)

    Meyer, C N; Svenson, M; Schade Larsen, C;

    2000-01-01

    Neutralizing cytokine antibodies are found in healthy and diseased individuals, including patients treated with recombinant cytokines. Identification of CCR-5 as co-receptor for HIV has focused interest on CC chemokines and their potential therapeutic use. Chemokine-binding components in plasma...... of HIV-infected patients were therefore assessed by radioimmunoassay and radioreceptor assay. IgG from 4/505 HIV patients and 9/2000 healthy controls (p>0.05) bound rMIP-1alpha and rMIP-1beta, but not rRANTES. No other plasma factors bound the chemokines. The antibodies inhibited receptor binding of both...... chemokines. There was no association between presence of antibodies and disease stage or HIV progression rate. Three of 11 patients treated with rIL-2 developed IgG antibodies suppressing cellular binding and growth promotion of rIL-2. Hence, circulating factors, including antibodies MIP-1alpha/MIP-1beta...

  11. A robust robotic high-throughput antibody purification platform.

    Science.gov (United States)

    Schmidt, Peter M; Abdo, Michael; Butcher, Rebecca E; Yap, Min-Yin; Scotney, Pierre D; Ramunno, Melanie L; Martin-Roussety, Genevieve; Owczarek, Catherine; Hardy, Matthew P; Chen, Chao-Guang; Fabri, Louis J

    2016-07-15

    Monoclonal antibodies (mAbs) have become the fastest growing segment in the drug market with annual sales of more than 40 billion US$ in 2013. The selection of lead candidate molecules involves the generation of large repertoires of antibodies from which to choose a final therapeutic candidate. Improvements in the ability to rapidly produce and purify many antibodies in sufficient quantities reduces the lead time for selection which ultimately impacts on the speed with which an antibody may transition through the research stage and into product development. Miniaturization and automation of chromatography using micro columns (RoboColumns(®) from Atoll GmbH) coupled to an automated liquid handling instrument (ALH; Freedom EVO(®) from Tecan) has been a successful approach to establish high throughput process development platforms. Recent advances in transient gene expression (TGE) using the high-titre Expi293F™ system have enabled recombinant mAb titres of greater than 500mg/L. These relatively high protein titres reduce the volume required to generate several milligrams of individual antibodies for initial biochemical and biological downstream assays, making TGE in the Expi293F™ system ideally suited to high throughput chromatography on an ALH. The present publication describes a novel platform for purifying Expi293F™-expressed recombinant mAbs directly from cell-free culture supernatant on a Perkin Elmer JANUS-VariSpan ALH equipped with a plate shuttle device. The purification platform allows automated 2-step purification (Protein A-desalting/size exclusion chromatography) of several hundred mAbs per week. The new robotic method can purify mAbs with high recovery (>90%) at sub-milligram level with yields of up to 2mg from 4mL of cell-free culture supernatant. PMID:27283099

  12. ABangle: characterising the VH-VL orientation in antibodies.

    Science.gov (United States)

    Dunbar, J; Fuchs, A; Shi, J; Deane, C M

    2013-10-01

    The binding site of an antibody is formed between the two variable domains, VH and VL, of its antigen binding fragment (Fab). Understanding how VH and VL orientate with respect to one another is important both for studying the mechanisms of antigen specificity and affinity and improving antibody modelling, docking and engineering. Different VH-VL orientations are commonly described using relative measures such as root-mean-square deviation. Recently, the orientation has also been characterised using the absolute measure of a VH-VL packing angle. However, a single angle cannot fully describe all modes of orientation. Here, we present a method which fully characterises VH-VL orientation in a consistent and absolute sense using five angles (HL, HC1, LC1, HC2 and LC2) and a distance (dc). Additionally, we provide a computational tool, ABangle, to allow the VH-VL orientation for any antibody to be automatically calculated and compared with all other known structures. We compare previous studies and show how the modes of orientation being identified relate to movements of different angles. Thus, we are able to explain why different studies identify different structural clusters and different residues as important. Given this result, we then identify those positions and their residue identities which influence each of the angular measures of orientation. Finally, by analysing VH-VL orientation in bound and unbound forms, we find that antibodies specific for protein antigens are significantly more flexible in their unbound form than antibodies specific for hapten antigens. ABangle is freely available at http://opig.stats.ox.ac.uk/webapps/abangle.

  13. A robust robotic high-throughput antibody purification platform.

    Science.gov (United States)

    Schmidt, Peter M; Abdo, Michael; Butcher, Rebecca E; Yap, Min-Yin; Scotney, Pierre D; Ramunno, Melanie L; Martin-Roussety, Genevieve; Owczarek, Catherine; Hardy, Matthew P; Chen, Chao-Guang; Fabri, Louis J

    2016-07-15

    Monoclonal antibodies (mAbs) have become the fastest growing segment in the drug market with annual sales of more than 40 billion US$ in 2013. The selection of lead candidate molecules involves the generation of large repertoires of antibodies from which to choose a final therapeutic candidate. Improvements in the ability to rapidly produce and purify many antibodies in sufficient quantities reduces the lead time for selection which ultimately impacts on the speed with which an antibody may transition through the research stage and into product development. Miniaturization and automation of chromatography using micro columns (RoboColumns(®) from Atoll GmbH) coupled to an automated liquid handling instrument (ALH; Freedom EVO(®) from Tecan) has been a successful approach to establish high throughput process development platforms. Recent advances in transient gene expression (TGE) using the high-titre Expi293F™ system have enabled recombinant mAb titres of greater than 500mg/L. These relatively high protein titres reduce the volume required to generate several milligrams of individual antibodies for initial biochemical and biological downstream assays, making TGE in the Expi293F™ system ideally suited to high throughput chromatography on an ALH. The present publication describes a novel platform for purifying Expi293F™-expressed recombinant mAbs directly from cell-free culture supernatant on a Perkin Elmer JANUS-VariSpan ALH equipped with a plate shuttle device. The purification platform allows automated 2-step purification (Protein A-desalting/size exclusion chromatography) of several hundred mAbs per week. The new robotic method can purify mAbs with high recovery (>90%) at sub-milligram level with yields of up to 2mg from 4mL of cell-free culture supernatant.

  14. Homogeneous plate based antibody internalization assay using pH sensor fluorescent dye.

    Science.gov (United States)

    Nath, Nidhi; Godat, Becky; Zimprich, Chad; Dwight, Stephen J; Corona, Cesear; McDougall, Mark; Urh, Marjeta

    2016-04-01

    Receptor-mediated antibody internalization is a key mechanism underlying several anti-cancer antibody therapeutics. Delivering highly toxic drugs to cancer cells, as in the case of antibody drug conjugates (ADCs), efficient removal of surface receptors from cancer cells and changing the pharmacokinetics profile of the antibody drugs are some of key ways that internalization impacts the therapeutic efficacy of the antibodies. Over the years, several techniques have been used to study antibody internalization including radiolabels, fluorescent microscopy, flow cytometry and cellular toxicity assays. While these methods allow analysis of internalization, they have limitations including a multistep process and limited throughput and are generally endpoint assays. Here, we present a new homogeneous method that enables time and concentration dependent measurements of antibody internalization. The method uses a new hydrophilic and bright pH sensor dye (pHAb dye), which is not fluorescent at neutral pH but becomes highly fluorescent at acidic pH. For receptor mediated antibody internalization studies, antibodies against receptors are conjugated with the pHAb dye and incubated with the cells expressing the receptors. Upon binding to the receptor, the dyes conjugated to the antibody are not fluorescent because of the neutral pH of the media, but upon internalization and trafficking into endosomal and lysosomal vesicles the pH drops and dyes become fluorescent. The enabling attributes of the pHAb dyes are the hydrophilic nature to minimize antibody aggregation and bright fluorescence at acidic pH which allows development of simple plate based assays using a fluorescent reader. Using two different therapeutic antibodies--Trastuzumab (anti-HER2) and Cetuximab (anti-EGFR)--we show labeling with pHAb dye using amine and thiol chemistries and impact of chemistry and dye to antibody ration on internalization. We finally present two new approaches using the pHAb dye, which will be

  15. Progression of Liver Disease

    Science.gov (United States)

    ... Browse Related Terms Progression of Liver Disease , Family History of Liver Disease , Liver Wellness , Liver Failure , Liver Biopsy Home > Your Liver > Liver Disease Information > The Progression ...

  16. C-C chemokine receptor-7 mediated endocytosis of antibody cargoes into intact cells

    Directory of Open Access Journals (Sweden)

    Xavier eCharest-Morin

    2013-09-01

    Full Text Available The C-C chemokine receptor-7 (CCR7 is a G protein coupled receptor that has a role in leukocyte homing, but that is also expressed in aggressive tumor cells. Preclinical research supports that CCR7 is a valid target in oncology. In view of the increasing availability of therapeutic monoclonal antibodies that carry cytotoxic cargoes, we studied the feasibility of forcing intact cells to internalize known monoclonal antibodies by exploiting the cycle of endocytosis and recycling triggered by the CCR7 agonist CCL19. Firstly, an anti-CCR7 antibody (CD197; clone 150503 labeled surface recombinant CCR7 expressed in intact HEK 293a cells and the fluorescent antibody was internalized following CCL19 treatment. Secondly, a recombinant myc-tagged CCL19 construction was exploited along the anti-myc monoclonal antibody 4A6. The myc-tagged ligand was produced as a conditioned medium of transfected HEK 293a cells that contained the equivalent of 430 ng/ml of immunoreactive CCL19 (average value, ELISA determination. CCL19-myc, but not authentic CCL19, carried the fluorophore-labeled antibody 4A6 into other recipient cells that expressed recombinant CCR7 (microscopy, cytofluorometry. The immune complexes were apparent in endosomal structures, colocalized well with the small GTPase Rab5 and progressed toward Rab7-positive endosomes. A dominant negative form of Rab5 (GDP-locked inhibited this endocytosis. Further, endosomes in CCL19-myc- or CCL19-stimulated cells were positive for β-arrestin2, but rarely for β-arrestin1. Following treatment with CCL19-myc and the 4A6 antibody, the melanoma cell line A375 that expresses endogenous CCR7 was specifically stained using a secondary peroxidase-conjugated antibody. Agonist-stimulated CCR7 can transport antibody-based cargoes, with possible therapeutic applications in oncology.

  17. Passive Immunization against HIV/AIDS by Antibody Gene Transfer

    Directory of Open Access Journals (Sweden)

    Lili Yang

    2014-01-01

    Full Text Available Despite tremendous efforts over the course of many years, the quest for an effective HIV vaccine by the classical method of active immunization remains largely elusive. However, two recent studies in mice and macaques have now demonstrated a new strategy designated as Vectored ImmunoProphylaxis (VIP, which involves passive immunization by viral vector-mediated delivery of genes encoding broadly neutralizing antibodies (bnAbs for in vivo expression. Robust protection against virus infection was observed in preclinical settings when animals were given VIP to express monoclonal neutralizing antibodies. This unorthodox approach raises new promise for combating the ongoing global HIV pandemic. In this article, we survey the status of antibody gene transfer, review the revolutionary progress on isolation of extremely bnAbs, detail VIP experiments against HIV and its related virus conduced in humanized mice and macaque monkeys, and discuss the pros and cons of VIP and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics.

  18. Investigating interactions between phospholipase B-Like 2 and antibodies during Protein A chromatography.

    Science.gov (United States)

    Tran, Benjamin; Grosskopf, Vanessa; Wang, Xiangdan; Yang, Jihong; Walker, Don; Yu, Christopher; McDonald, Paul

    2016-03-18

    Purification processes for therapeutic antibodies typically exploit multiple and orthogonal chromatography steps in order to remove impurities, such as host-cell proteins. While the majority of host-cell proteins are cleared through purification processes, individual host-cell proteins such as Phospholipase B-like 2 (PLBL2) are more challenging to remove and can persist into the final purification pool even after multiple chromatography steps. With packed-bed chromatography runs using host-cell protein ELISAs and mass spectrometry analysis, we demonstrated that different therapeutic antibodies interact to varying degrees with host-cell proteins in general, and PLBL2 specifically. We then used a high-throughput Protein A chromatography method to further examine the interaction between our antibodies and PLBL2. Our results showed that the co-elution of PLBL2 during Protein A chromatography is highly dependent on the individual antibody and PLBL2 concentration in the chromatographic load. Process parameters such as antibody resin load density and pre-elution wash conditions also influence the levels of PLBL2 in the Protein A eluate. Furthermore, using surface plasmon resonance, we demonstrated that there is a preference for PLBL2 to interact with IgG4 subclass antibodies compared to IgG1 antibodies. PMID:26896920

  19. Learning numerical progressions.

    Science.gov (United States)

    Vitz, P C; Hazan, D N

    1974-01-01

    Learning of simple numerical progressions and compound progressions formed by combining two or three simple progressions is investigated. In two experiments, time to solution was greater for compound vs simple progressions; greater the higher the progression's solution level; and greater if the progression consisted of large vs small numbers. A set of strategies is proposed to account for progression learning based on the assumption S computes differences between integers, differences between differences, etc., in a hierarchical fashion. Two measures of progression difficulty, each a summary of the strategies, are proposed; C1 is a count of the number of differences needed to solve a progression; C2 is the same count with higher level differences given more weight. The measures accurately predict in both experiments the mean time to solve 16 different progressions with C2 being somewhat superior. The measures also predict the learning difficulty of 10 other progressions reported by Bjork (1968).

  20. Idiotypic network. Assay and use of anti-idiotype antibodies in medicine

    International Nuclear Information System (INIS)

    After a brief history of idotypes, the structural basis of antibody and T cell receptor (Ti) diversity, the definition of various types of idiotopes, the idiotypic cascade and the network concept are presented. Some anti-idiotypic antibodies represent the internal image of the antigen and may be used to prepare anti-idiotypic vaccines. Other anti-idiotypic antibodies bind to cellular receptors and can mimick or antagonize the biological effects of the natural ligands (hormones, neurotransmitters etc...). The concept of regulatory idiotopes (Idx) and their use in the manipulation of the network offer new possibilities for the control for auto-antibody production. The main medical applications of idiotypy are briefly considered including cancer, transplantation, allergy and auto-immune diseases. Finally the methodology applicable to the detection and titration of anti-idiotypes is described

  1. Miller-Fisher Syndrome: Are Anti-GAD Antibodies Implicated in Its Pathophysiology?

    Directory of Open Access Journals (Sweden)

    Ioannis E. Dagklis

    2016-01-01

    Full Text Available Miller-Fisher syndrome (MFS is considered as a variant of the Guillain-Barre syndrome (GBS and its characteristic clinical features are ophthalmoplegia, ataxia, and areflexia. Typically, it is associated with anti-GQ1b antibodies; however, a significant percentage (>10% of these patients are seronegative. Here, we report a 67-year-old female patient who presented with the typical clinical features of MFS. Workup revealed antibodies against glutamic acid decarboxylase (GAD in relatively high titers while GQ1b antibodies were negative. Neurological improvement was observed after intravenous gamma globulin and follow-up examinations showed a continuous clinical amelioration with simultaneous decline of anti-GAD levels which finally returned to normal values. This case indicates that anti-GAD antibodies may be associated with a broader clinical spectrum and future studies in GQ1b-seronegative patients could determine ultimately their clinical and pathogenetic significance in this syndrome.

  2. Characterization of a Novel Neutralizing Monoclonal Antibody Against Ebola Virus GP.

    Science.gov (United States)

    Reynard, Olivier; Volchkov, Viktor E

    2015-10-01

    Ebola virus is the etiological agent of a severe hemorrhagic fever with a high mortality rate. As the only protein exposed on the surface of viral particles, the spike glycoprotein GP is the unique target for neutralizing monoclonal antibodies. In this study, we demonstrate the strong neutralization capacity of the monoclonal antibody #3327 and characterize its activity. GP residues that are required for recognition and neutralization were found to be located both in the internal fusion loop and in the receptor-binding domain. Analysis of Ebola virus entry in the presence of #3327 allows us to hypothesize that this antibody binds to the virus particle before internalization and endosomal processing of GP and likely prevents the final viral fusion step. Importantly, #3327 is able to block entry of virions bearing GP that contain the Q508 escape mutation common to a number of virus-neutralizing antibodies, and therefore provides future perspectives for treatment strategies against Ebola virus infection.

  3. Recombinant approaches to IgG-like bispecific antibodies

    Institute of Scientific and Technical Information of China (English)

    Jonathan S MARVIN; Zhenping ZHU

    2005-01-01

    One of the major obstacles in the development of bispecific antibodies (BsAb)has been the difficulty of producing the materials in sufficient quality and quantity by traditional technologies, such as the hybrid hybridoma and chemical conjugation methods. In contrast to the rapid and significant progress in the development of recombinant BsAb fragments (such as diabody and tandem single chain Fv), the successful design and production of full length IgG-like BsAb has been limited. Compared to smaller fragments, IgG-like BsAb have long serum halflife and are capable of supporting secondary immune functions, such as antibody-dependent cellular cytotoxicity and complement-mediated cytotoxicity. The development of IgG-like BsAb as therapeutic agents will depend heavily on our research progress in the design of recombinant BsAb constructs (or formats) and production efficiency. This review will focus on recent advances in various recombinant approaches to the engineering and production of IgG-like BsAb.

  4. Clinical significance of detection of antibodies to fetal and adult acetylcholine receptors in myasthenia gravis

    Institute of Scientific and Technical Information of China (English)

    Qi-Guang Shi; Zhi-Hong Wang; Xiao-Wei Ma; Da-Qi Zhang; Chun-Sheng Yang; Fu-Dong Shi; Li Yang

    2012-01-01

    Objective To evaluate the frequency,distribution and clinical significance of the antibodies to the fetal and/or adult acetylcholine receptor (AChR) in patients with myasthenia gravis (MG).Methods AChR antibodies were detected by cell-based assay in the serum of ocular MG (OMG) (n =90) and generalized MG (GMG) patients (n =110).The fetaltype (2α∶ β∶ γ∶ δ) and adult-type (2α∶ β∶ ε∶ δ) AChR were used as antigens,and their relevance to disease presentation was assessed.Results The overall frequencies of anti-adult and anti-fetal AChR antibodies were similar in all 200 patients examined,with 14 having serum specific to the AChR-γ subunit,and 22 to the AChR-ε subunit.The overall sensitivity when using the fetal and adult AChR antibodies was higher than that when using the fetal AChR antibody only (P =0.015).Compared with OMG patients,the mean age at disease onset and the positive ratio of antibodies to both isoforms of the AChR were significantly higher in patients who subsequently progressed to GMG.Older patients and patients with both anti-fetal and anti-adult AChR antibodies had a greater risk for developing generalized disease [odds ratio (OR),1.03;95% confidence interval (CI),1.01-1.06 and OR,5.09;95% CI,2.23-11.62].Conclusion Using both fetal-and adulttype AChRs as the antigens may be more sensitive than using either subtype.Patients with serum specific to both isoforms are at a greater risk of progressing to GMG.Patients with disease onset at an advanced age appear to have a higher frequency of GMG conversion.

  5. [New immunological weapons for medicine in the 21st Century: biological therapy based on the use of the latest generation monoclonal antibodies].

    Science.gov (United States)

    Aguillón, Juan C; Contreras, Juan; Dotte, Andrés; Cruzat, Andrea; Catalán, Diego; Salazar, Lorena; Molina, María Carmen; Guerrero, Julia; López, Mercedes; Soto, Lilian; Salazar-Onfray, Flavio; Cuchacovich, Miguel

    2003-12-01

    The fusion of a murine B cell and a myeloma cell generates a hybridoma that produces monoclonal antibody (mAb). These murine mAb induce the HAMA (human anti-mouse antibodies) response. Murine mAb have been modified by genetic engineering, producing molecules with a higher proportion of human protein. At present, chimeric, humanized and fully human mAb are available. mAb block interactions between target molecules and their ligands or trigger the lyses of mAb-coated tumor cells. Numerous mAb have been developed using the recombinant DNA technology and several are available in the market. Trastuzumab, against HER2/neu, is useful in breast cancer; rituximab, against CD20 in B lymphocytes is useful in lymphoma; alemtuzumah, against CD52 is used in lymphoma and leukemia; daclizumab and basiliximab block the IL-2 receptor interaction and reduce acute rejection in kidney transplantation; abciximab, an antagonist of GPIIb/IIIa platelet receptor, is used in patients undergoing acute coronary syndromes. In autoimmunity diseases, blocking tumor necrosis factor by infliximab and adalimumab has demonstrated excellent results. Thus, infliximab is useful in the treatment of rheumatoid arthritis (RA), Crohn's disease and ulcerative colitis while adalimumab is the first fully human mAb available for RA. Infliximab and adalimumab reduce signs and symptoms in RA and they also interfere with progression of joint damage. Finally, the direct benefits of antagonist treatment can occur at the expense of a major adverse effect in some other biological function.

  6. Missing Links in Antibody Assembly Control

    Directory of Open Access Journals (Sweden)

    Tiziana Anelli

    2013-01-01

    Full Text Available Fidelity of the humoral immune response requires that quiescent B lymphocytes display membrane bound immunoglobulin M (IgM on B lymphocytes surface as part of the B cell receptor, whose function is to recognize an antigen. At the same time B lymphocytes should not secrete IgM until recognition of the antigen has occurred. The heavy chains of the secretory IgM have a C-terminal tail with a cysteine instead of a membrane anchor, which serves to covalently link the IgM subunits by disulfide bonds to form “pentamers” or “hexamers.” By virtue of the same cysteine, unassembled secretory IgM subunits are recognized and retained (via mixed disulfide bonds by members of the protein disulfide isomerase family, in particular ERp44. This so-called “thiol-mediated retention” bars assembly intermediates from prematurely leaving the cell and thereby exerts quality control on the humoral immune response. In this essay we discuss recent findings on how ERp44 governs such assembly control in a pH-dependent manner, shuttling between the cisGolgi and endoplasmic reticulum, and finally on how pERp1/MZB1, possibly as a co-chaperone of GRP94, may help to overrule the thiol-mediated retention in the activated B cell to give way to antibody secretion.

  7. Controlled delivery of antibodies from injectable hydrogels.

    Science.gov (United States)

    Fletcher, Nathan A; Babcock, Lyndsey R; Murray, Ellen A; Krebs, Melissa D

    2016-02-01

    Therapeutic antibodies are currently used for the treatment of various diseases, but large doses delivered systemically are typically required. Localized controlled delivery techniques would afford major benefits such as decreasing side effects and required doses. Injectable biopolymer systems are an attractive solution due to their minimally invasive potential for controlled release in a localized area. Here, alginate-chitosan hydrogels are demonstrated to provide controlled delivery of IgG model antibodies and also of Fab antibody fragments. Also, an alternate delivery system comprised of poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with antibodies and encapsulated in alginate was shown to successfully provide another level of control over release. These biopolymer systems that offer controlled delivery for antibodies and antibody fragments will be promising for many applications in drug delivery and regenerative medicine.

  8. Factors determining antibody distribution in tumors

    Science.gov (United States)

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

    2009-01-01

    The development of antibody therapies for cancer is increasing rapidly, primarily owing to their specificity. Antibody distribution in tumors is often extremely uneven, however, leading to some malignant cells being exposed to saturating concentrations of antibody, whereas others are completely untargeted. This is detrimental because large regions of cells escape therapy, whereas other regions might be exposed to suboptimal concentrations that promote a selection of resistant mutants. The distribution of antibody depends on a variety of factors, including dose, affinity, antigens per cell and molecular size. Because these parameters are often known or easily estimated, a quick calculation based on simple modeling considerations can predict the uniformity of targeting within a tumor. Such analyses should enable experimental researchers to identify in a straightforward way the limitations in achieving evenly distributed antibody, and design and test improved antibody therapeutics more rationally. PMID:18179828

  9. Stabilization of antibody fragments in adverse environments.

    Science.gov (United States)

    Dooley, H; Grant, S D; Harris, W J; Porter, A J

    1998-08-01

    Antibody fragments have the potential to be used as sensitive and specific binding agents in a broad range of industrial applications. Genetic manipulation has been used to design a series of antibody fragment configurations with a flexible linker and/or a disulphide bond between the heavy chain and light chain of an antibody fragment against the herbicide atrazine. The thermostability and stability to a range of denaturants, polar and non-polar solvents, surfactants and proteases have been compared. It has been found that a novel antibody fragment construct (STAB: stabilized antibody) containing both a flexible linker and a disulphide bond can be effectively produced and shows greatly improved stability in these diverse environments. These STABs should be useful in environmental diagnostics and remediation, and may provide a generic approach for stabilizing antibody fragments in formulations containing detergents and penetrants for topical application in the pharmaceutical and cosmetic industries.

  10. Towards On-site Pathogen Detection Using Antibody-based Sensors

    DEFF Research Database (Denmark)

    Skottrup, Peter Durand; Nicolaisen, Mogens; Justesen, Annemarie Fejer

    2008-01-01

    In this paper the recent progress within biosensors for plant pathogen detection will be reviewed. Bio-recognition layers on sensors can be designed in various ways, however the most popular approach is to immobilise antibodies for specific capture of analytes. Focus will be put on antibody surfa...... monocytogenes, Streptococcus mutans, Bacillus cereus, Bacillus anthracis, Campylobacter and Escherichia coli. We will touch upon optimal assay design and further discuss the strengths and limitations of current sensor technologies for detection of viruses, bacteria and fungi....

  11. [Anti-NEP and anti-PLA2R antibodies in membranous nephropathy: an update].

    Science.gov (United States)

    Pozdzik, A A; Debiec, H; I Brochériou; Husson, C; Rorive, S; Broeders, N; Le Moine, A; Ronco, P; Nortier, J

    2015-01-01

    Membranous nephropathy (MN) is the most common cause for nephrotic syndrome in adults and occurs as an idiopathic (primary) or secondary disease. Since the early 2000's, substantial advances have been made in the understanding of the molecular bases of MN. The neutral endopeptidase (NEP) and the receptor for secretory phospholipase A2 (PLA2R) have been identified as target antigens for circulating and deposited antibodies in allo-immune neonatal and adult " idiopathic " MN, respectively. These antibodies recognize specific antigens of podocytes, precipitate as subepithelial immune complexes and activate complement leading to proteinuria. Anti-PLA2R antibodies are of particular clinical importance. Indeed, they are detected in approximately 70% of primary MN in adults, demonstrating that MN actually is an autoimmune condition specific to the kidney. In Europeans, genome-wide studies have shown an association between alleles of PLA2R1 and HLA DQA1 (class II genes of tissue histocompatibility complex) genes and idiopathic MN. Newly developed diagnostic tests detecting circulating anti-PLA2R antibody and PLA2R antigen in glomerular deposits have induced a change in paradigm in the diagnostic approach of idiopathic MN. Measurement of circulating anti-PLA2R antibody is also very useful for the monitoring of MN activity. However, the mechanisms responsible for the formation of anti-PLA2R antibodies as well as those involved in the progression of MN to end-stage renal disease remain to be defined.

  12. Novel method for the high-throughput production of phosphorylation site-specific monoclonal antibodies

    Science.gov (United States)

    Kurosawa, Nobuyuki; Wakata, Yuka; Inobe, Tomonao; Kitamura, Haruki; Yoshioka, Megumi; Matsuzawa, Shun; Kishi, Yoshihiro; Isobe, Masaharu

    2016-01-01

    Threonine phosphorylation accounts for 10% of all phosphorylation sites compared with 0.05% for tyrosine and 90% for serine. Although monoclonal antibody generation for phospho-serine and -tyrosine proteins is progressing, there has been limited success regarding the production of monoclonal antibodies against phospho-threonine proteins. We developed a novel strategy for generating phosphorylation site-specific monoclonal antibodies by cloning immunoglobulin genes from single plasma cells that were fixed, intracellularly stained with fluorescently labeled peptides and sorted without causing RNA degradation. Our high-throughput fluorescence activated cell sorting-based strategy, which targets abundant intracellular immunoglobulin as a tag for fluorescently labeled antigens, greatly increases the sensitivity and specificity of antigen-specific plasma cell isolation, enabling the high-efficiency production of monoclonal antibodies with desired antigen specificity. This approach yielded yet-undescribed guinea pig monoclonal antibodies against threonine 18-phosphorylated p53 and threonine 68-phosphorylated CHK2 with high affinity and specificity. Our method has the potential to allow the generation of monoclonal antibodies against a variety of phosphorylated proteins. PMID:27125496

  13. Geothermal progress monitor. Progress report No. 1

    Energy Technology Data Exchange (ETDEWEB)

    1979-12-01

    Progress is reported on the following: electrical uses, direct-heat uses, drilling activities, leases, geothermal loan guarantee program, general activities, and legal, institutional, and regulatory activites. (MHR)

  14. A peptide mimic blocks the cross-reaction of anti-DNA antibodies with glomerular antigens.

    Science.gov (United States)

    Xia, Y; Eryilmaz, E; Der, E; Pawar, R D; Guo, X; Cowburn, D; Putterman, C

    2016-03-01

    Anti-DNA antibodies play a pivotal role in the pathogenesis of lupus nephritis by cross-reacting with renal antigens. Previously, we demonstrated that the binding affinity of anti-DNA antibodies to self-antigens is isotype-dependent. Furthermore, significant variability in renal pathogenicity was seen among a panel of anti-DNA isotypes [derived from a single murine immunoglobulin (Ig)G3 monoclonal antibody, PL9-11] that share identical variable regions. In this study, we sought to select peptide mimics that effectively inhibit the binding of all murine and human anti-DNA IgG isotypes to glomerular antigens. The PL9-11 panel of IgG anti-DNA antibodies (IgG1, IgG2a, IgG2b and IgG3) was used for screening a 12-mer phage display library. Binding affinity was determined by surface plasmon resonance. Enzyme-linked immunosorbent assay (ELISA), flow cytometry and glomerular binding assays were used for the assessment of peptide inhibition of antibody binding to nuclear and kidney antigens. We identified a 12 amino acid peptide (ALWPPNLHAWVP, or 'ALW') which binds to all PL9-11 IgG isotypes. Preincubation with the ALW peptide reduced the binding of the PL9-11 anti-DNA antibodies to DNA, laminin, mesangial cells and isolated glomeruli significantly. Furthermore, we confirmed the specificity of the amino acid sequence in the binding of ALW to anti-DNA antibodies by alanine scanning. Finally, ALW inhibited the binding of murine and human lupus sera to dsDNA and glomeruli significantly. In conclusion, by inhibiting the binding of polyclonal anti-DNA antibodies to autoantigens in vivo, the ALW peptide (or its derivatives) may potentially be a useful approach to block anti-DNA antibody binding to renal tissue.

  15. Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies.

    Directory of Open Access Journals (Sweden)

    Amy E Gilbert

    Full Text Available Melanoma, a potentially lethal skin cancer, is widely thought to be immunogenic in nature. While there has been much focus on T cell-mediated immune responses, limited knowledge exists on the role of mature B cells. We describe an approach, including a cell-based ELISA, to evaluate mature IgG antibody responses to melanoma from human peripheral blood B cells. We observed a significant increase in antibody responses from melanoma patients (n = 10 to primary and metastatic melanoma cells compared to healthy volunteers (n = 10 (P<0.0001. Interestingly, we detected a significant reduction in antibody responses to melanoma with advancing disease stage in our patient cohort (n = 21 (P<0.0001. Overall, 28% of melanoma patient-derived B cell cultures (n = 1,800 compared to 2% of cultures from healthy controls (n = 600 produced antibodies that recognized melanoma cells. Lastly, a patient-derived melanoma-specific monoclonal antibody was selected for further study. This antibody effectively killed melanoma cells in vitro via antibody-mediated cellular cytotoxicity. These data demonstrate the presence of a mature systemic B cell response in melanoma patients, which is reduced with disease progression, adding to previous reports of tumor-reactive antibodies in patient sera, and suggesting the merit of future work to elucidate the clinical relevance of activating humoral immune responses to cancer.

  16. Monoclonal antibodies as diagnostics; an appraisal

    Directory of Open Access Journals (Sweden)

    Siddiqui M

    2010-01-01

    Full Text Available Ever since the development of Hybridoma Technology in 1975 by Kohler and Milstein, our vision for antibodies as tools for research for prevention, detection and treatment of diseases, vaccine production, antigenic characterization of pathogens and in the study of genetic regulation of immune responses and disease susceptibility has been revolutionized. The monoclonal antibodies being directed against single epitopes are homogeneous, highly specific and can be produced in unlimited quantities. In animal disease diagnosis, they are very useful for identification and antigenic characterization of pathogens. Monoclonal antibodies have tremendous applications in the field of diagnostics, therapeutics and targeted drug delivery systems, not only for infectious diseases caused by bacteria, viruses and protozoa but also for cancer, metabolic and hormonal disorders. They are also used in the diagnosis of lymphoid and myeloid malignancies, tissue typing, enzyme linked immunosorbent assay, radio immunoassay, serotyping of microorganisms, immunological intervention with passive antibody, antiidiotype inhibition, or magic bullet therapy with cytotoxic agents coupled with anti mouse specific antibody. Recombinant deoxyribonucleic acid technology through genetic engineering has successfully led to the possibility of reconstruction of monoclonal antibodies viz. chimeric antibodies, humanized antibodies and complementarily determining region grafted antibodies and their enormous therapeutic use.

  17. Snake venom antibodies in Ecuadorian Indians.

    Science.gov (United States)

    Theakston, R D; Reid, H A; Larrick, J W; Kaplan, J; Yost, J A

    1981-10-01

    Serum samples from 223 Waorani Indians, a tribe in eastern Ecuador, were investigated by enzyme-linked immunosorbent assay for antibodies to snake venom. Seventy-eight per cent were positive, confirming the highest incidence and mortality from snake bite poisoning yet recorded in the world. Most samples were positive for more than one venom antibody. Antibodies were found to venoms of Bothrops viper in 60% of positive cases, of Micrurus coral snake in 21%, and of the bushmaster, Lachesis muta, in 18%. Further studies are needed to determine whether high venom-antibody levels afford protection against further snake envenoming. PMID:7299877

  18. Sequence and structual analysis of antibodies.

    OpenAIRE

    Raghavan, A. K.

    2008-01-01

    The work presented in this thesis focuses on the sequence and structural analysis of antibodies and has fallen into three main areas. First I developed a method to assess how typical an antibody sequence is of the expressed human antibody repertoire. My hypothesis was that the more "human like" an antibody sequence is (in other words how typical it is of the expressed human repertoire), the less likely it is to elicit an immune response when used in vivo in humans. In practice, I found that, ...

  19. Antiphospholipid Antibodies and Systemic Scleroderma

    Directory of Open Access Journals (Sweden)

    Awa Oumar Touré

    2013-03-01

    Full Text Available Objective: Antiphospholipid antibodies (APLs could be associated with an increased risk of vascular pathologies in systemic scleroderma. The aim of our study was to search for APLs in patients affected by systemic scleroderma and to evaluate their involvement in the clinical manifestations of this disease. Materials and Methods: We conducted a cross-sectional descriptive study, from January 2009 until August 2010, with patients received at the Department of Dermatology (Dakar, Senegal. Blood samples were taken at the hematology laboratory and were analyzed for the presence of APLs. Results: Forty patients were recruited. Various types of either isolated or associated APLs were found in 23 patients, i.e. 57.5% of the study population. The most frequently encountered antibody was IgG anti-β2 GPI (37.5% of the patients, followed by anticardiolipins (17.5% and lupus anticoagulants (5%. No statistically significant association of positive antiphospholipid-related tests to any of the scleroderma complications could be demonstrated. Conclusion: A high proportion of patients showing association of systemic scleroderma and APLs suggests the presence of a morbid correlation between these 2 pathologies. It would be useful to follow a cohort of patients affected by systemic scleroderma in order to monitor vascular complications following confirmation of the presence of antiphospholipid syndrome.

  20. A Comparison of Anti-Nuclear Antibody Quantification Using Automated Enzyme Immunoassays and Immunofluorescence Assays

    DEFF Research Database (Denmark)

    Baronaite, Renata; Engelhart, Merete; Mørk Hansen, Troels;

    2014-01-01

    using IFA and automated EIA techniques. The IFA results generated by two independent laboratories were compared with the EIA results from antibodies against double-stranded DNA (dsDNA), from ANA screening, and from tests of the seven included subantigens. The final IFA and EIA results for 386 unique...

  1. Antibodies to human fetal erythroid cells from a nonimmune phage antibody library

    OpenAIRE

    Huie, Michael A.; Cheung, Mei-Chi; Muench, Marcus O.; Becerril, Baltazar; Kan, Yuet W.; Marks, James D.

    2001-01-01

    The ability to isolate fetal nucleated red blood cells (NRBCs) from the maternal circulation makes possible prenatal genetic analysis without the need for diagnostic procedures that are invasive for the fetus. Such isolation requires antibodies specific to fetal NRBCs. To generate a panel of antibodies to antigens present on fetal NRBCs, a new type of nonimmune phage antibody library was generated in which multiple copies of antibody fragments are displayed on each pha...

  2. High level transient production of recombinant antibodies and antibody fusion proteins in HEK293 cells

    OpenAIRE

    Jäger, Volker; Büssow, Konrad; Wagner, Andreas; Weber, Susanne; Hust, Michael; Frenzel, André; Schirrmann, Thomas

    2013-01-01

    Background The demand of monospecific high affinity binding reagents, particularly monoclonal antibodies, has been steadily increasing over the last years. Enhanced throughput of antibody generation has been addressed by optimizing in vitro selection using phage display which moved the major bottleneck to the production and purification of recombinant antibodies in an end-user friendly format. Single chain (sc)Fv antibody fragments require additional tags for detection and are not as suitable...

  3. Loss of autonoetic consciousness of recent autobiographical episodes and accelerated long-term forgetting in a patient with previously unrecognized glutamic acid decarboxylase antibody related limbic encephalitis

    Directory of Open Access Journals (Sweden)

    Juri-Alexander eWitt

    2015-06-01

    Full Text Available We describe a 35-year old male patient presenting with depressed mood and emotional instability who complained about severe anterograde and retrograde memory deficits characterized by accelerated long-term forgetting and loss of autonoetic consciousness regarding autobiographical memories of the last three years. Months before he had experienced two breakdowns of unknown etiology giving rise to the differential diagnosis of epileptic seizures after various practitioners and clinics had suggested different etiologies such as a psychosomatic condition, burnout, depression or dissociative amnesia. Neuropsychological assessment indicated selectively impaired figural memory performance. Extended diagnostics confirmed accelerated forgetting of previously learned and retrievable verbal material. Structural imaging showed bilateral swelling and signal alterations of temporomesial structures (left > right. Video-EEG monitoring revealed a left temporal epileptic focus and subclincal seizure, but no overt seizures. Antibody tests in serum and liquor were positive for glutamic acid decarboxylase antibodies. These findings led to the diagnosis of glutamic acid decarboxylase antibody related limbic encephalitis. Monthly steroid pulses over six months led to recovery of subjective memory and to intermediate improvement but subsequent worsening of objective memory performance. During the course of treatment the patient reported de novo paroxysmal non-responsive states. Thus, antiepileptic treatment was started and the patient finally became seizure free. At the last visit vocational reintegration was successfully in progress.In conclusion, amygdala swelling, retrograde biographic memory impairment, accelerated long-term forgetting and emotional instability may serve as indicators of limbic encephalitis, even in the absence of overt epileptic seizures. The monitoring of such patients calls for a standardized and concerted multilevel diagnostic approach with

  4. Final Progress Report for FG02-89ER14030

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, Maureen R

    2011-10-26

    Intracellular Dynamics of Energy-Transducing Organelles. The location and interaction of intracellular organelles is important for exchange of substrate and product between compartments for optimum functioning of biochemical pathways and energy transduction. Plastids and stromules, tubular plastid extensions, are highly dynamic in many plant tissues. Stromules can connect two or more plastids and proteins and macromolecular complexes can be transferred between them. Stromules have been observed to form close contacts with other organelles, the plasma membrane, and can pass through channels in the nucleus. Chloroplasts move in response to light and mechanical stimulus. Especially in non-green cells, plastids change shape and position, and stromules extend and retract. Stromules appear to be involved in recycling of chloroplast proteins when photosynthesis is limited, through an autophagic process that results in degradation of portions of the stromal contents without complete destruction of the chloroplast. Mutations in several genes known to mediate chloroplast division result in altered stromule morphology in some cells. Plastid and stromule motility is mediated by the actin cytoskeleton. The possible role of myosins in chloroplast movement was investigated by labeling the cargo-binding tails of six Arabidopsis myosin XI proteins with yellow fluorescent protein (YFP). The fluorescent proteins were found to localize to vesicles and peroxisomes. The portion of the myosin tail domain fused to YFP affected whether specific or non-specific localization was observed. In contrast to experiments in animal cells, movement of labeled organelles was not entirely inhibited by expression of defective myosin in which the motor domain was replaced with a fluorescent protein. None of the six myosin proteins tested labeled plastids or chloroplasts. However, the Arabidopsis myosin XI gene family expresses an additional seven myosins that await further examination. These experiments have provided more information on stromule formation and function and the actin-myosin machinery that mediates the intracellular trafficking that is required for photosynthesis and metabolism to operate efficiently within the plant cell.

  5. Fourth international workshop on human chromosome 5. Final progress report

    Energy Technology Data Exchange (ETDEWEB)

    McPherson, J.D.

    1996-12-31

    The Fourth International Workshop on Human Chromosome 5 was held in Manchester, UK on November 9--10, 1996 and was hosted by the University of Manchester. The major goals of the workshop were: (1) to collate the various genetic, cytogenetic and physical maps of human chromosome 5; (2) to integrate these maps and identify/correct discrepancies between them wherever possible; (3) to catalogue the sequence-ready contigs of the chromosome; (4) to co-ordinate the various sequencing efforts to avoid future duplication; (5) to establish the first (to the author`s knowledge) web site for the human chromosome 5 community which contains the above information in a readily accessible form.

  6. Final Progress Report for the activity called AMO2010 committee

    Energy Technology Data Exchange (ETDEWEB)

    Donald Shapero; Michael Moloney

    2006-12-31

    The committee was charged to produce a comprehensive report on the status of AMO Science. The committee was charged to produce a report that: 1. Reviewed the field of AMO science, emphasize recent accomplishments, and identify new opportunities and compelling scientific questions; 2. Identified the impact of AMO science on other scientific fields, emerging technologies, and national needs; 3. Identified future workforce, societal and educational needs for AMO science; and 4. Made recommendations on how the US research enterprise might realize the full potential of AMO science. The committee also produced an intermediate report addressing key research issues and themes facing the research community.

  7. HARNESS: Heterogeneous Adaptable Reconfigurable Networked Systems. Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Fagg, G. E.

    2004-01-20

    HARNESS was proposed as a system that combined the best of emerging technologies found in current distributed computing research and commercial products into a very flexible, dynamically adaptable framework that could be used by applications to allow them to evolve and better handle their execution environment. The HARNESS system was designed using the considerable experience from previous projects such as PVM, MPI, IceT and Cumulvs. As such, the system was designed to avoid any of the common problems found with using these current systems, such as no single point of failure, ability to survive machine, node and software failures. Additional features included improved intercomponent connectivity, with full support for dynamic down loading of addition components at run-time thus reducing the stress on application developers to build in all the libraries they need in advance.

  8. Inventors Center of Michigan Technical Assessment Program. Final progress report

    Energy Technology Data Exchange (ETDEWEB)

    1992-12-31

    The Technical Assessment Program at the Inventors Center of Michigan is designed to provide independent inventors with a reliable assessment of the technical merits of their proposed inventions. Using faculty from within Ferris State University`s College of Technology an assessment process examines the inventor`s assumptions, documentation, and prototypes, as well as, reviewing patent search results and technical literature to provide the inventor with a written report on the technical aspects of the proposed invention. The forms for applying for a technical assessment of an invention are included.

  9. Final Progress Report - Heavy Ion Accelerator Theory and Simulation

    Energy Technology Data Exchange (ETDEWEB)

    Haber, Irving

    2009-10-31

    The use of a beam of heavy ions to heat a target for the study of warm dense matter physics, high energy density physics, and ultimately to ignite an inertial fusion pellet, requires the achievement of beam intensities somewhat greater than have traditionally been obtained using conventional accelerator technology. The research program described here has substantially contributed to understanding the basic nonlinear intense-beam physics that is central to the attainment of the requisite intensities. Since it is very difficult to reverse intensity dilution, avoiding excessive dilution over the entire beam lifetime is necessary for achieving the required beam intensities on target. The central emphasis in this research has therefore been on understanding the nonlinear mechanisms that are responsible for intensity dilution and which generally occur when intense space-charge-dominated beams are not in detailed equilibrium with the external forces used to confine them. This is an important area of study because such lack of detailed equilibrium can be an unavoidable consequence of the beam manipulations such as acceleration, bunching, and focusing necessary to attain sufficient intensity on target. The primary tool employed in this effort has been the use of simulation, particularly the WARP code, in concert with experiment, to identify the nonlinear dynamical characteristics that are important in practical high intensity accelerators. This research has gradually made a transition from the study of idealized systems and comparisons with theory, to study the fundamental scaling of intensity dilution in intense beams, and more recently to explicit identification of the mechanisms relevant to actual experiments. This work consists of two categories; work in direct support beam physics directly applicable to NDCX and a larger effort to further the general understanding of space-charge-dominated beam physics.

  10. Non-destructive determination of trace elements. Final progress report

    International Nuclear Information System (INIS)

    In the course of this project we have successfully designed, built, and tested the first neutron beam facility dedicated to routine multielement neutron capture prompt-γ activation analysis (PGAA). This technique is capable of accurately measuring concentrations of up to 20 elements in a number of sample types, and is an extremely valuable complement to instrumental neutron activation analysis (INAA) and other analytical methods. We have found PGAA to have some major advantages over INAA: (1) the sample is subjected to neutron fluxes about five orders of magnitude less than in PGAA, with essentially no radiation or heating damage; (2) as the data are taken during sample irradiation, analyses can be performed immediately instead of waiting up to four weeks as in INAA; (3) it is capable of measuring all major elements, except oxygen, in many samples, including H, C, N, and Si, which cannot be done by INAA; and (4) it is especially sensitive for the trace elements B, Cd, Sm and Gd. In addition, we have characterized the overall capabilities of PGAA and the corrections necessary to make it an extremely accurate technique. We have applied PGAA in a number of studies in which it has proved to be extremely valuable and, at times, even providing crucial information that other techniques were incapable of supplying. 1 fig., 6 tabs

  11. Rooftop PV system. Final technical progress report, Phase II

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-08-01

    Under this four-year PV:BONUS Program, ECD and United Solar are developing and demonstrating two new lightweight flexible building integrated Photovoltaic (BIPV) modules specifically designed as exact replacements for conventional asphalt shingles and standing seam metal roofing. These modules can be economically and aesthetically integrated into new residential and commercial buildings, and address the even larger roofing replacement market. The modules are designed to be installed by roofing contractors without special training which minimizes the installation and balance of system costs. The modules will be fabricated from high-efficiency, multiple-junction a-Si alloy solar cells developed by ECD and United Solar. Under the Phase I Program, which ended in March 1994, we developed two different concept designs for rooftop PV modules: (1) the United Solar overlapping (asphalt shingle replacement) shingle-type modules and (2) the ECD metal roof-type modules. We also developed a plan for fabricating, testing and demonstrating these modules. Candidate demonstration sites for our rooftop PV modules were identified and preliminary engineering designs for these demonstrations were developed; a marketing study plan was also developed. The major objectives of the Phase II Program, which started in June 1994 was (1) to develop, test, and qualify these new rooftop modules; (2) to develop mechanical and electrical engineering specifications for the demonstration projects; and (3) to develop a marketing/commercialization plan.

  12. Gene transcription and electromagnetic fields. Final progress report

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, A.S.

    1992-12-31

    Our overall aim is to obtain sufficient information to allow us to ultimately determine whether ELF EM field exposure is an initiating factor in neoplastic transformation and/or if exposure can mimic characteristics of the second-step counterpart in neoplastic disease. This aim is based on our previous findings that levels of some transcripts are increased in cells exposed to EM fields. While the research is basic in nature, the ramifications have bearing on the general safety of exposure to EM fields in industrial and everyday life. A large array of diverse biological effects are reported to occur as the result of exposure to elf EM fields, suggesting that the cell response to EM fields is at a basic level, presumably initiated by molecular and/or biophysical events at the cell membrane. The hypothesized route is a signal transduction pathway involving membrane calcium fluxes. Information flow resulting from signal transduction can mediate the induction of regulatory factors in the cell, and directly affect how transcription is regulated.

  13. Progress in diagnosis of neuromyelitis optica

    Directory of Open Access Journals (Sweden)

    ZHONG Xiao-nan

    2012-04-01

    Full Text Available Neuromyelitis optica (NMO is an autoimmune disease of central nervous system involving the optic nerves and spinal. It was considered an optic-spinal form of multiple sclerosis (MS until serum anti-aquaporin-4 antibody (NMO-IgG were suggested to be a specific biomarker of NMO, distinguishing it from MS. Longitudinally extensive transverse myelitis (LETM is suggested to be one of the most characteristic spinal cord lesions of NMO. Wingerchuk criteria and criteria recommended by National Multiple Sclerosis Society (NMSS task force on differential diagnosis of MS are two main diagnostic criteria of NMO. This review discusses the recent progress in diagnosis of NMO.

  14. Recent progress in dengue vaccine development

    Institute of Scientific and Technical Information of China (English)

    Jianchun; Wei; Hui; Chen; Jing; An

    2014-01-01

    Dengue virus(DENV) has four distinct serotypes. DENV infection can result in classic dengue fever and life-threatening dengue hemorrhagic fever/dengue shock syndrome. In recent decades, DENV infection has become an important public health concern in epidemic-prone areas. Vaccination is the most effective measure to prevent and control viral infections. However, several challenges impede the development of effective DENV vaccines, such as the lack of suitable animal models and the antibody-dependent enhancement phenomenon. Although no licensed DENV vaccine is available, significant progress has been made. This review summarizes candidate DENV vaccines from recent investigations.

  15. Recent progress in dengue vaccine development.

    Science.gov (United States)

    Wei, Jianchun; Chen, Hui; An, Jing

    2014-12-01

    Dengue virus (DENV) has four distinct serotypes. DENV infection can result in classic dengue fever and life-threatening dengue hemorrhagic fever/dengue shock syndrome. In recent decades, DENV infection has become an important public health concern in epidemic-prone areas. Vaccination is the most effective measure to prevent and control viral infections. However, several challenges impede the development of effective DENV vaccines, such as the lack of suitable animal models and the antibody-dependent enhancement phenomenon. Although no licensed DENV vaccine is available, significant progress has been made. This review summarizes candidate DENV vaccines from recent investigations. PMID:25547681

  16. Polyclonal antibody cocktails generated using DNA vaccine technology protect in murine models of orthopoxvirus disease

    Directory of Open Access Journals (Sweden)

    Ballantyne John

    2011-09-01

    Full Text Available Abstract Background Previously we demonstrated that DNA vaccination of nonhuman primates (NHP with a small subset of vaccinia virus (VACV immunogens (L1, A27, A33, B5 protects against lethal monkeypox virus challenge. The L1 and A27 components of this vaccine target the mature virion (MV whereas A33 and B5 target the enveloped virion (EV. Results Here, we demonstrated that the antibodies produced in vaccinated NHPs were sufficient to confer protection in a murine model of lethal Orthopoxvirus infection. We further explored the concept of using DNA vaccine technology to produce immunogen-specific polyclonal antibodies that could then be combined into cocktails as potential immunoprophylactic/therapeutics. Specifically, we used DNA vaccines delivered by muscle electroporation to produce polyclonal antibodies against the L1, A27, A33, and B5 in New Zealand white rabbits. The polyclonal antibodies neutralized both MV and EV in cell culture. The ability of antibody cocktails consisting of anti-MV, anti-EV, or a combination of anti-MV/EV to protect BALB/c mice was evaluated as was the efficacy of the anti-MV/EV mixture in a mouse model of progressive vaccinia. In addition to evaluating weight loss and lethality, bioimaging technology was used to characterize the spread of the VACV infections in mice. We found that the anti-EV cocktail, but not the anti-MV cocktail, limited virus spread and lethality. Conclusions A combination of anti-MV/EV antibodies was significantly more protective than anti-EV antibodies alone. These data suggest that DNA vaccine technology could be used to produce a polyclonal antibody cocktail as a possible product to replace vaccinia immune globulin.

  17. Surface plasmon resonance biosensing: Approaches for screening and characterising antibodies for food diagnostics.

    Science.gov (United States)

    Yakes, B J; Buijs, J; Elliott, C T; Campbell, K

    2016-08-15

    Research in biosensing approaches as alternative techniques for food diagnostics for the detection of chemical contaminants and foodborne pathogens has increased over the last twenty years. The key component of such tests is the biorecognition element whereby polyclonal or monoclonal antibodies still dominate the market. Traditionally the screening of sera or cell culture media for the selection of polyclonal or monoclonal candidate antibodies respectively has been performed by enzyme immunoassays. For niche toxin compounds, enzyme immunoassays can be expensive and/or prohibitive methodologies for antibody production due to limitations in toxin supply for conjugate production. Automated, self-regenerating, chip-based biosensors proven in food diagnostics may be utilised as rapid screening tools for antibody candidate selection. This work describes the use of both single channel and multi-channel surface plasmon resonance (SPR) biosensors for the selection and characterisation of antibodies, and their evaluation in shellfish tissue as standard techniques for the detection of domoic acid, as a model toxin compound. The key advantages in the use of these biosensor techniques for screening hybridomas in monoclonal antibody production were the real time observation of molecular interaction and rapid turnaround time in analysis compared to enzyme immunoassays. The multichannel prototype instrument was superior with 96 analyses completed in 2h compared to 12h for the single channel and over 24h for the ELISA immunoassay. Antibodies of high sensitivity, IC50's ranging from 4.8 to 6.9ng/mL for monoclonal and 2.3-6.0ng/mL for polyclonal, for the detection of domoic acid in a 1min analysis time were selected. Although there is a progression for biosensor technology towards low cost, multiplexed portable diagnostics for the food industry, there remains a place for laboratory-based SPR instrumentation for antibody development for food diagnostics as shown herein. PMID:27260435

  18. 抗CATSPER1抗体对精子运动的影响%The Influence of CATSPER1 Antibody to the Sperm Motility

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

      目的探讨CATSPER1蛋白在精子运动中的功能。方法将正常精液标本与终浓度分别为0.8μg/mL、4μg/mL、20μg/mL的CATSPER1抗体混合孵育,然后于37℃1h、2h、6h用计算机辅助分析系统(CASA)进行精液参数分析。结果在不同时间,前向运动精子(a+b级)、快速前向运动精子(a级)的百分比均较对照组明显减少并且成剂量依赖性,慢速前向运动精子(b级)受抗体抑制的作用不明显。结论 CATSPER1在精子运动过程中发挥重要功能,CATSPER1抗体主要抑制精子快速前向运动能力。% Objective Objective: To evaluate the function of cation channel of sperm 1 (CATSPER1) protein in human sperm motility; Methods The sperm samples from normozoospermic donors were incucbated with different CATSPER1 antibody at final concentrations of 0,0.8,4,20μg/mL.Sperm motility was measured by means of computer-assisted semen analysis after 1, 2 and 6 hours incubation at 37℃. Results Progressive motility (class a+b) and fast progressive motility (class a) of sperm were both inhibited under the use of CATSPER1 antibody in different concentrations and significant dose-dependent changes were observed (respectively, P<0.01 and P<0.05)and slow motility sperms were not inhibited at different time. Conclusion CATSPER1 protein plays an important role in maintaining the motility of mature sperm of which fast progressive motility can be inhibited by CATSPER1 antibody.

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

    NARCIS (Netherlands)

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

    2003-01-01

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

  20. Optical imaging of disseminated leukemia models in mice with near-infrared probe conjugated to a monoclonal antibody.

    Directory of Open Access Journals (Sweden)

    Sabrina Pesnel

    Full Text Available BACKGROUND: The assessment of anticancer agents to treat leukemia needs to have animal models closer to the human pathology such as implantation in immunodeficient mice of leukemic cells from patient samples. A sensitive and early detection of tumor cells in these orthotopic models is a prerequisite for monitoring engraftment of leukemic cells and their dissemination in mice. Therefore, we developed a fluorescent antibody based strategy to detect leukemic foci in mice bearing patient-derived leukemic cells using fluorescence reflectance imaging (FRI to determine when to start treatments with novel antitumor agents. METHODS: Two mAbs against the CD44 human myeloid marker or the CD45 human leukocyte marker were labeled with Alexa Fluor 750 and administered to leukemia-bearing mice after having verified the immunoreactivity in vitro. Bioluminescent leukemic cells (HL60-Luc were used to compare the colocalization of the fluorescent mAb with these cells. The impact of the labeled antibodies on disease progression was further determined. Finally, the fluorescent hCD45 mAb was tested in mice engrafted with human leukemic cells. RESULTS: The probe labeling did not modify the immunoreactivity of the mAbs. There was a satisfactory correlation between bioluminescence imaging (BLI and FRI and low doses of mAb were sufficient to detect leukemic foci. However, anti-hCD44 mAb had a strong impact on the tumor proliferation contrary to anti-hCD45 mAb. The use of anti-hCD45 mAb allowed the detection of leukemic patient cells engrafted onto NOD/SCID mice. CONCLUSIONS: A mAb labeled with a near infrared fluorochrome is useful to detect leukemic foci in disseminated models provided that its potential impact on tumor proliferation has been thoroughly documented.

  1. Optical Imaging of Disseminated Leukemia Models in Mice with Near-Infrared Probe Conjugated to a Monoclonal Antibody

    Science.gov (United States)

    Pesnel, Sabrina; Pillon, Arnaud; Créancier, Laurent; Lerondel, Stéphanie; Le Pape, Alain; Recher, Christian; Demur, Cécile; Guilbaud, Nicolas; Kruczynski, Anna

    2012-01-01

    Background The assessment of anticancer agents to treat leukemia needs to have animal models closer to the human pathology such as implantation in immunodeficient mice of leukemic cells from patient samples. A sensitive and early detection of tumor cells in these orthotopic models is a prerequisite for monitoring engraftment of leukemic cells and their dissemination in mice. Therefore, we developed a fluorescent antibody based strategy to detect leukemic foci in mice bearing patient-derived leukemic cells using fluorescence reflectance imaging (FRI) to determine when to start treatments with novel antitumor agents. Methods Two mAbs against the CD44 human myeloid marker or the CD45 human leukocyte marker were labeled with Alexa Fluor 750 and administered to leukemia-bearing mice after having verified the immunoreactivity in vitro. Bioluminescent leukemic cells (HL60-Luc) were used to compare the colocalization of the fluorescent mAb with these cells. The impact of the labeled antibodies on disease progression was further determined. Finally, the fluorescent hCD45 mAb was tested in mice engrafted with human leukemic cells. Results The probe labeling did not modify the immunoreactivity of the mAbs. There was a satisfactory correlation between bioluminescence imaging (BLI) and FRI and low doses of mAb were sufficient to detect leukemic foci. However, anti-hCD44 mAb had a strong impact on the tumor proliferation contrary to anti-hCD45 mAb. The use of anti-hCD45 mAb allowed the detection of leukemic patient cells engrafted onto NOD/SCID mice. Conclusions A mAb labeled with a near infrared fluorochrome is useful to detect leukemic foci in disseminated models provided that its potential impact on tumor proliferation has been thoroughly documented. PMID:22303450

  2. Technical progress report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-10-01

    This report summarizes experimental and theoretical work in basic nuclear physics carried out between October 1, 1995, the closing of our last Progress Report, and September 30, 1996 at the Nuclear Physics Laboratory of the University of Colorado, Boulder, under contracts DE-FG03-93ER-40774 and DE-FG03-95ER-40913 with the United States Department of Energy. The experimental contract supports broadly-based experimental research in intermediate energy nuclear physics. This report includes results from studies of Elementary Systems involving the study of the structure of the nucleon via polarized high-energy positron scattering (the HERMES experiment) and lower energy pion scattering from both polarized and unpolarized nucleon targets. Results from pion- and kaon-induced reactions in a variety of nuclear systems are reported under the section heading Meson Reactions; the impact of these and other results on understanding the nucleus is presented in the Nuclear Structure section. In addition, new results from scattering of high-energy electrons (from CEBAF/TJNAF) and pions (from KEK) from a broad range of nuclei are reported in the section on Incoherent Reactions. Finally, the development and performance of detectors produced by the laboratory are described in the section titled Instrumentation.

  3. Technical progress report

    International Nuclear Information System (INIS)

    This report summarizes experimental and theoretical work in basic nuclear physics carried out between October 1, 1995, the closing of our last Progress Report, and September 30, 1996 at the Nuclear Physics Laboratory of the University of Colorado, Boulder, under contracts DE-FG03-93ER-40774 and DE-FG03-95ER-40913 with the United States Department of Energy. The experimental contract supports broadly-based experimental research in intermediate energy nuclear physics. This report includes results from studies of Elementary Systems involving the study of the structure of the nucleon via polarized high-energy positron scattering (the HERMES experiment) and lower energy pion scattering from both polarized and unpolarized nucleon targets. Results from pion- and kaon-induced reactions in a variety of nuclear systems are reported under the section heading Meson Reactions; the impact of these and other results on understanding the nucleus is presented in the Nuclear Structure section. In addition, new results from scattering of high-energy electrons (from CEBAF/TJNAF) and pions (from KEK) from a broad range of nuclei are reported in the section on Incoherent Reactions. Finally, the development and performance of detectors produced by the laboratory are described in the section titled Instrumentation

  4. METAL BINDING PROPERTIES OF A MONOCLONAL ANTIBODY DIRECTED TOWARDS METAL-CHELATE COMPLEXES. (R824029)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  5. Progress in ITER Construction

    International Nuclear Information System (INIS)

    Full text: Since the entry into force of the ITER Agreement in October 2007, the ITER Organization and the Domestic Agencies have made significant progress in the finalization of the ITER design and the establishment of the baseline. This paper will describe the main advances and achievements since the last IAEA conference. The Integrated Project Schedule has gone through a number of iterations following interactions with Domestic Agencies and their industries. With operating a First Plasma at the end of 2019 construction will be finished and the functionality of all major components will be demonstrated. Through a series of operation and installation campaigns in the following seven years full DT operation should be reached by 2026. The associated resource estimate for the cost of the ITER Organization has been reviewed by an independent panel and has been developed using common project management practices. Attention has been paid to the development of risk based assessments of the schedule giving confidence that this schedule can be achieved if no major unforeseen events happen. The ITER platform has been prepared by Agence ITER France and was finalized by the summer of 2009. The next stage will be the start of the excavation and construction of the anti-seismic support structure for the tokamak building. The road between the harbor of Marseille and the Cadarache site is ready to receive the first test convoys. Just under 90% of the components for ITER will provided in-kind by the Members through so-called Procurement Arrangements, which are bi-lateral agreements between the ITER Organization and the Domestic Agencies. Until now 34 Procurement Arrangements have been signed, representing almost half of the value of the total in-kind contributions. The first Procurement Arrangements concentrated on the long-lead items, such as the Magnet systems, Buildings and the Vacuum Vessel. Most of the Procurement Arrangements for these long-lead items have now been

  6. 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.

  7. 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.

  8. "Unconventional" Neutralizing Activity of Antibodies Against HIV

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

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

  9. Photonic crystal fiber based antibody detection

    DEFF Research Database (Denmark)

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

    2004-01-01

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

  10. Monoclonal antibodies reactive with hairy cell leukemia

    NARCIS (Netherlands)

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

    1989-01-01

    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. Antibod

  11. Recent developments in antibody-based assays for the detection of bacterial toxins.

    Science.gov (United States)

    Zhu, Kui; Dietrich, Richard; Didier, Andrea; Doyscher, Dominik; Märtlbauer, Erwin

    2014-04-11

    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.

  12. Specific Monoclonal Antibody Overcomes the Salmonella enterica Serovar Typhimurium's Adaptive Mechanisms of Intramacrophage Survival and Replication.

    Directory of Open Access Journals (Sweden)

    Swarmistha Devi Aribam

    Full Text Available Salmonella-specific antibodies play an important role in host immunity; however, the mechanisms of Salmonella clearance by pathogen-specific antibodies remain to be completely elucidated since previous studies on antibody-mediated protection have yielded inconsistent results. These inconsistencies are at least partially attributable to the use of polyclonal antibodies against Salmonella antigens. Here, we developed a new monoclonal antibody (mAb-449 and identified its related immunogen that protected BALB/c mice from infection with Salmonella enterica serovar Typhimurium. In addition, these data indicate that the mAb-449 immunogen is likely a major protective antigen. Using in vitro infection studies, we also analyzed the mechanism by which mAb-449 conferred host protection. Notably, macrophages infected with mAb-449-treated S. Typhimurium showed enhanced pathogen uptake compared to counterparts infected with control IgG-treated bacteria. Moreover, these macrophages produced elevated levels of pro-inflammatory cytokine TNFα and nitric oxide, indicating that mAb-449 enhanced macrophage activation. Finally, the number of intracellular bacteria in mAb-449-activated macrophages decreased considerably, while the opposite was found in IgG-treated controls. Based on these findings, we suggest that, although S. Typhimurium has the potential to survive and replicate within macrophages, host production of a specific antibody can effectively mediate macrophage activation for clearance of intracellular bacteria.

  13. Synthetic Antibodies for Reversible Cell Recognition

    Science.gov (United States)

    Zhou, Jing Zhou

    2011-12-01

    Antibody-mediated cell recognition plays a critical role in various biological and biomedical applications. However, strong antibody-cell interactions can lead to the difficulty of separating antibodies from the bound cells in a simple and non-destructive manner, which is often necessary to numerous applications such as cell sorting or separation. Thus, this thesis research is aimed to create an antibody-like nanomaterial with the function of reversible cell recognition It was hypothesized that nucleic acid aptamer and dendrimer could be used as fundamental structural components to develop an antibody-like nanomaterial. The aptamer functions as the binding site of an antibody; the dendrimer is used as a robust, defined nano-scaffold to support the aptamer and to carry small molecules (e.g., fluorophores). To test this hypothesis, a novel method was first developed to discover the essential nucleotides of full-length aptamers to mimic the binding sites of antibodies. The essential nucleotides were further conjugated with a dendrimer to synthesize a monovalent aptamer-dendrimer nanomaterial. The results clearly showed that the essential nucleotides could maintain high affinity and specificity after tethered on dendrimer surface. To further test the hypothesis that antibody-like nanomaterials can be rationally designed to acquire the capability of reversible cell recognition, an aptamer that was selected at 0 °C was used as a model to synthesize a "Y-shaped" nanomaterial by conjugating two aptamers to the same dendrimer. The results showed that the nanomaterial-cell interaction could be affected by the distance between two binding aptamers. In addition, the "Y-shaped" antibody-like nanomaterial could bind target cells more strongly than its monovalent control. Importantly, the strong cell-nanomaterial interaction could be rapidly reversed when the temperature was shifted from 0 °C to 37 °C. In summary, we developed a synthetic antibody that can not only mimic the

  14. Trends in Malignant Glioma Monoclonal Antibody Therapy

    Science.gov (United States)

    Chekhonin, Ivan; Gurina, Olga

    2015-01-01

    Although new passive and active immunotherapy methods are emerging, unconjugated monoclonal antibodies remain the only kind of biological preparations approved for high-grade glioma therapy in clinical practice. In this review, we combine clinical and experimental data discussion. As antiangiogenic therapy is the standard of care for recurrent glioblastoma multiforme (GBM), we analyze major clinical trials and possible therapeutic combinations of bevacizumab, the most common monoclonal antibody to vascular endothelial growth factor (VEGF). Another humanized antibody to gain recognition in GBM is epidermal growth factor (EGFR) antagonist nimotuzumab. Other antigens (VEGF receptor, platelet-derived growth factor receptor, hepatocyte growth factor and c-Met system) showed significance in gliomas and were used to create monoclonal antibodies applied in different malignant tumors. We assess the role of genetic markers (isocitrate dehydrogenase, O6-methylguanine-DNA methyltransnsferase) in GBM treatment outcome prediction. Besides antibodies studied in clinical trials, we focus on perspective targets and briefly list other means of passive immunotherapy.

  15. 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.

  16. Progress against Prostate Cancer

    Science.gov (United States)

    ... this page please turn Javascript on. Feature: Prostate Cancer Progress Against Prostate Cancer Past Issues / Winter 2010 Table of Contents ... Read More "Prostate Cancer" Articles Progress Against Prostate Cancer / Prostate Cancer Research Trial Helps John Spencer Treat His ...

  17. Vector-Mediated In Vivo Antibody Expression.

    Science.gov (United States)

    Schnepp, Bruce C; Johnson, Philip R

    2014-08-01

    This article focuses on a novel vaccine strategy known as vector-mediated antibody gene transfer, with a particular focus on human immunodeficiency virus (HIV). This strategy provides a solution to the problem of current vaccines that fail to generate neutralizing antibodies to prevent HIV-1 infection and AIDS. Antibody gene transfer allows for predetermination of antibody affinity and specificity prior to "immunization" and avoids the need for an active humoral immune response against the HIV envelope protein. This approach uses recombinant adeno-associated viral (rAAV) vectors, which have been shown to transduce muscle with high efficiency and direct the long-term expression of a variety of transgenes, to deliver the gene encoding a broadly neutralizing antibody into the muscle. Following rAAV vector gene delivery, the broadly neutralizing antibodies are endogenously synthesized in myofibers and passively distributed to the circulatory system. This is an improvement over classical passive immunization strategies that administer antibody proteins to the host to provide protection from infection. Vector-mediated gene transfer studies in mice and monkeys with anti-HIV and simian immunodeficiency virus (SIV)-neutralizing antibodies demonstrated long-lasting neutralizing activity in serum with complete protection against intravenous challenge with virulent HIV and SIV. These results indicate that existing potent anti-HIV antibodies can be rapidly moved into the clinic. However, this methodology need not be confined to HIV. The general strategy of vector-mediated antibody gene transfer can be applied to other difficult vaccine targets such as hepatitis C virus, malaria, respiratory syncytial virus, and tuberculosis. PMID:26104192

  18. Immobilization of antibodies and enzyme-labeled antibodies by radiation polymerization

    International Nuclear Information System (INIS)

    Immobilization of antibodies and enzyme-labeled antibodies by radiation polymerization at low temperatures was studied. The antibody activity of antibody was not affected by irradiation at an irradiation dose of below 8 MR and low temperatures. Immobilization of peroxidase-labeled anti-rabbit IgG goat IgG, anti-peroxidase, peroxidase, and anti-alpha-fetoprotein was carried out with hydrophilic and hydrophobic monomers. The activity of the immobilized enzyme-labeled antibody membranes varied with the thickness of the membranes and increased with decreasing membrane thickness. The activity of the immobilized antibody particles was varied by particle size. Immobilized anti-alpha-fetoprotein particles and membranes can be used for the assay of alpha-fetoprotein by the antigen-antibody reaction, such as a solid-phase sandwich method with high sensitivity

  19. 1984-85 ISN progress report

    International Nuclear Information System (INIS)

    This progress report ISN 1984-1985 deals with the following subjects: nuclear physics theory, peripheral and intermediate energy physics, characteristics of reaction mechanisms in heavy ion collisions, nuclear structure, fundamental interactions, experimental methods and new instrumentation, some interdisciplinary research activities and technical activities, the SARA cyclotron and finally, technology transfer and valorisation

  20. Activity Progress report 1982-1985

    International Nuclear Information System (INIS)

    This reports gives a summary of all activities of the Elementary Particle Physics Department at Saclay between the beginning of 1982 and the end of 1985. The experiments in progress or in preparation are presented by subject. The main technical studies and achievements are also described. Finally lists of publications and information concerning Department organization are given

  1. Celiac anti-type 2 transglutaminase antibodies induce phosphoproteome modification in intestinal epithelial Caco-2 cells.

    Directory of Open Access Journals (Sweden)

    Gaetana Paolella

    Full Text Available BACKGROUND: Celiac disease is an inflammatory condition of the small intestine that affects genetically predisposed individuals after dietary wheat gliadin ingestion. Type 2-transglutaminase (TG2 activity seems to be responsible for a strong autoimmune response in celiac disease, TG2 being the main autoantigen. Several studies support the concept that celiac anti-TG2 antibodies may contribute to disease pathogenesis. Our recent findings on the ability of anti-TG2 antibodies to induce a rapid intracellular mobilization of calcium ions, as well as extracellular signal-regulated kinase phosphorylation, suggest that they potentially act as signaling molecules. In line with this concept, we have investigated whether anti-TG2 antibodies can induce phosphoproteome modification in an intestinal epithelial cell line. METHODS AND PRINCIPAL FINDINGS: We studied phosphoproteome modification in Caco-2 cells treated with recombinant celiac anti-TG2 antibodies. We performed a two-dimensional electrophoresis followed by specific staining of phosphoproteins and mass spectrometry analysis of differentially phosphorylated proteins. Of 14 identified proteins (excluding two uncharacterized proteins, three were hypophosphorylated and nine were hyperphosphorylated. Bioinformatics analyses confirmed the presence of phosphorylation sites in all the identified proteins and highlighted their involvement in several fundamental biological processes, such as cell cycle progression, cell stress response, cytoskeletal organization and apoptosis. CONCLUSIONS: Identification of differentially phosphorylated proteins downstream of TG2-antibody stimulation suggests that in Caco-2 cells these antibodies perturb cell homeostasis by behaving as signaling molecules. We hypothesize that anti-TG2 autoantibodies may destabilize the integrity of the intestinal mucosa in celiac individuals, thus contributing to celiac disease establishment and progression. Since several proteins here

  2. Radiohalogenated half-antibodies and maleimide intermediate therefor

    Science.gov (United States)

    Kassis, A.I.; Khawli, L.A.

    1991-02-19

    N-(m-radiohalophenyl) maleimide can be conjugated with a reduced antibody having a mercapto group to provide a radiolabeled half-antibody having immunological specific binding characteristics of whole antibody. No Drawings

  3. The impact of pretransplant donor-specific antibodies on graft outcome in renal transplantation: a six-year follow-up study

    Directory of Open Access Journals (Sweden)

    Elias David-Neto

    2012-01-01

    Full Text Available OBJECTIVE: The significance of pretransplant, donor-specific antibodies on long-term patient outcomes is a subject of debate. This study evaluated the impact and the presence or absence of donor-specific antibodies after kidney transplantation on short- and long-term graft outcomes. METHODS: We analyzed the frequency and dynamics of pretransplant donor-specific antibodies following renal transplantation from a randomized trial that was conducted from 2002 to 2004 and correlated these findings with patient outcomes through 2009. Transplants were performed against a complement-dependent T- and B-negative crossmatch. Pre- and posttransplant sera were available from 94 of the 118 patients (80%. Antibodies were detected using a solid-phase (LuminexH, single-bead assay, and all tests were performed simultaneously. RESULTS: Sixteen patients exhibited pretransplant donor-specific antibodies, but only 3 of these patients (19% developed antibody-mediated rejection and 2 of them experienced early graft losses. Excluding these 2 losses, 6 of 14 patients exhibited donor-specific antibodies at the final follow-up exam, whereas 8 of these patients (57% exhibited complete clearance of the donor-specific antibodies. Five other patients developed ''de novo'' posttransplant donor-specific antibodies. Death-censored graft survival was similar in patients with pretransplant donor-specific and non-donor-specific antibodies after a mean follow-up period of 70 months. CONCLUSION: Pretransplant donor-specific antibodies with a negative complement-dependent cytotoxicity crossmatch are associated with a risk for the development of antibody-mediated rejection, although survival rates are similar when patients transpose the first months after receiving the graft. Our data also suggest that early posttransplant donor-specific antibody monitoring should increase knowledge of antibody dynamics and their impact on long-term graft outcome.

  4. Improvement of a low pH antigen-antibody dissociation procedure for ELISA measurement of circulating anti-Aβ antibodies

    Directory of Open Access Journals (Sweden)

    Ugen Kenneth E

    2007-03-01

    Full Text Available Abstract Background Prior work from our group found that acid dissociation (pH 2.5 incubation of serum from APP transgenic mice vaccinated against Aβ increased the apparent anti-Aβ titers, suggesting antibody masking by antigen in the ELISA assay. Subsequently, we found that pH 2.5 incubation of serum from unvaccinated non-transgenic mice showed antibody binding to Aβ1–42, but no increase when other proteins, including shorter Aβ peptides, coated the ELISA plate. To investigate further the effects of low pH incubation on apparent anti-Aβ1–42 signals, we examined normal sera from nonTg unvaccinated mice, nonTg mice vaccinated with Aβ peptide (to produce authentic anti-Aβ antibodies or a monoclonal antibody against Aβ (6E10 using competitive-inhibition ELISA and Aβ epitope mapping assays. In addition, we examined use of a less stringent low pH procedure at pH 3.5, to ascertain if it had the same effects as the pH 2.5 procedure. Results We believe there are three distinct effects of pH 2.5 incubation.; A an artifactual increase in binding to full length Aβ by mouse immunoglobulin which has low affinity for Aβ, B an inactivation of anti-Aβ antibodies that is time dependent and C unmasking of high affinity anti-Aβ antibodies when high levels of circulating Aβ is present in APP transgenic mice. All three reactions can interact to produce the final ELISA signal. Incubation of sera from unvaccinated nonTg mice at pH 2.5 enhanced ELISA signals by process A. Conversely, pH 2.5 incubation of sera from vaccinated nonTg mice with caused a time dependent reduction of antibody signal by process B (overcoming the increase caused by A. The artifactual anti-Aβ ELISA signal enhanced by pH 2.5 incubation of normal mouse sera could not be effectively competed by low to moderate concentrations of Aβ, nor bind to shorter Aβ peptides in a manner similar to authentic anti-Aβ antibodies. Incubation of mouse sera at pH 3.5 caused neither an apparent

  5. Role of oxidative stress and autoimmunity in onset and progression of vitiligo.

    Science.gov (United States)

    Laddha, Naresh C; Dwivedi, Mitesh; Mansuri, Mohmmad Shoab; Singh, Mala; Gani, Amina R; Yeola, Asmita P; Panchal, Vipul N; Khan, Fazal; Dave, Darshana J; Patel, Ananddeep; Madhavan, Shajil E; Gupta, Richa; Marfatia, Zarna; Marfatia, Yogesh S; Begum, Rasheedunnisa

    2014-05-01

    Vitiligo is an acquired depigmentation disorder characterized by the loss of functional melanocytes from the epidermis. Two major theories of vitiligo pathogenesis include autoimmunity and oxidative stress-mediated toxicity in melanocytes. The present study aimed to evaluate both the hypotheses in vitiligo patients and to investigate their role in the disease onset and progression. Antimelanocyte antibody levels and lipid peroxidation (LPO) levels were evaluated in 427 patients and 440 controls; antithyroid peroxidase (TPO) antibody levels were estimated in 102 patients and 72 controls. Patients showed a significant increase in LPO and antimelanocyte antibody levels compared to controls. Antimelanocyte antibody and LPO levels were higher in active vitiligo compared to stable. Only 9.8% of patients showed the presence of anti-TPO antibodies in their circulation. Oxidative stress may be the initial triggering event to precipitate vitiligo in Gujarat population, which is exacerbated by contributing autoimmune factors together with oxidative stress.

  6. Antinuclear antibody testing: discordance between commercial laboratories.

    Science.gov (United States)

    Abeles, Aryeh M; Gomez-Ramirez, Manuel; Abeles, Micha; Honiden, Shyoko

    2016-07-01

    Antinuclear antibody (ANA) test results frequently affect the course of patients' evaluations, diagnosis, and treatment, but different laboratory centers may yield conflicting results. This study investigated the degree of agreement between laboratory results in a group of subjects who had ANA testing performed at two commercial laboratories. This was a chart review study, in which all ANA tests ordered by the authors from one commercial laboratory over a 4-year period were queried. Corresponding patient charts were reviewed, and if ANA testing had also been performed at the second commercial laboratory, subjects were entered into the study. The primary measurement was agreement between paired ANA results, and we performed sensitivity analysis using varying criteria defining agreement (criteria A to criteria D [strictest to most lenient definition of agreement]). Other data captured included relevant data obtained through the course of evaluation (e.g., presenting complaints, exam findings, other laboratory data) and final diagnoses. Of 101 paired ANA tests, there was 18 % agreement according to the strictest criteria and 42 % according to the most lenient. Of the seven subjects with ANA-associated rheumatic disease, none of the paired tests were in agreement according to criteria A (two agreed according to criteria D). Our findings demonstrate poor agreement between paired ANA tests performed at two commercial laboratories. The low level of agreement may have far-reaching clinical implications. Specifically, this finding calls into question the reliability of ANA testing as it is currently performed and suggests that results may in part depend upon the laboratory center to which patients are referred. PMID:27044430

  7. Antibody Engineering & Therapeutics, the annual meeting of The Antibody Society December 7-10, 2015, San Diego, CA, USA.

    Science.gov (United States)

    Pauthner, Matthias; Yeung, Jenny; Ullman, Chris; Bakker, Joost; Wurch, Thierry; Reichert, Janice M; Lund-Johansen, Fridtjof; Bradbury, Andrew R M; Carter, Paul J; Melis, Joost P M

    2016-01-01

    The 26th Antibody Engineering & Therapeutics meeting, the annual meeting of The Antibody Society united over 800 participants from all over the world in San Diego from 6-10 December 2015. The latest innovations and advances in antibody research and development were discussed, covering a myriad of antibody-related topics by more than 100 speakers, who were carefully selected by The Antibody Society. As a prelude, attendees could join the pre-conference training course focusing, among others, on the engineering and enhancement of antibodies and antibody-like scaffolds, bispecific antibody engineering and adaptation to generate chimeric antigen receptor constructs. The main event covered 4 d of scientific sessions that included antibody effector functions, reproducibility of research and diagnostic antibodies, new developments in antibody-drug conjugates (ADCs), preclinical and clinical ADC data, new technologies and applications for bispecific antibodies, antibody therapeutics for non-cancer and orphan indications, antibodies to harness the cellular immune system, building comprehensive IgVH-gene repertoires through discovering, confirming and cataloging new germline IgVH genes, and overcoming resistance to clinical immunotherapy. The Antibody Society's special session focused on "Antibodies to watch" in 2016. Another special session put the spotlight on the limitations of the new definitions for the assignment of antibody international nonproprietary names introduced by the World Health Organization. The convention concluded with workshops on computational antibody design and on the promise and challenges of using next-generation sequencing for antibody discovery and engineering from synthetic and in vivo libraries. PMID:26909869

  8. Utilisation of antibody microarrays for the selection of specific and informative antibodies from recombinant library binders of unknown quality

    DEFF Research Database (Denmark)

    Kibat, Janek; Schirrmann, Thomas; Knape, Matthias J;

    2016-01-01

    Many diagnostic and therapeutic concepts require antibodies of high specificity. Recombinant binder libraries and related selection approaches allow the efficient isolation of antibodies against almost every target of interest. Nevertheless, it cannot be guaranteed that selected antibodies perfor...

  9. Combinatorial antibody libraries: new advances, new immunological insights.

    Science.gov (United States)

    Lerner, Richard A

    2016-08-01

    Immunochemists have become quite proficient in engineering existing antibody molecules to control their pharmacological properties. However, in terms of generating new antibodies, the combinatorial antibody library has become a central feature of modern immunochemistry. These libraries are essentially an immune system in a test tube and enable the selection of antibodies without the constraints of whole animal or cell-based systems. This Review provides an overview of how antibody libraries are constructed and discusses what can be learnt from these synthetic systems. In particular, the Review focuses on new biological insights from antibody libraries - such as the concept of 'SOS antibodies' - and the growing use of intracellular antibodies to perturb cellular functions.

  10. Factors influencing the uptake of a new monoclonal antibody (LICR-LON-M8) in skeletal metastases from breast carcinoma

    International Nuclear Information System (INIS)

    Preliminary studies with an In 111 labelled monoclonal antibody to Human Milk Fat Globule Membrane (LICR-LON-M8) showed successful localisation of breast carcinoma bone metastases without the necessity of blood background subtraction. A further 18 patients with breast carcinoma have been investigated to elucidate in more detail the factors influencing the uptake of antibody. All patients had serial bone scintigrams and X-rays in addition to the antibody scintigrams at 18-48 hours after injection. The M8 was labelled with In 111 DTPA. Thirteen sites were positive on the antibody scintigrams alone. In X-ray positive lesions (25) antibody scintigrams were more often positive in lytic (15) than sclerotic (5) or mixed (5) lesions. In nine cases the focal disease was smaller than 2 cm but five larger focal lesions were negative. Correlative studies showed that positive antibody scintigrams were found in new lesions or progressive disease preceding X-ray or positive bone scintigrams. In a few patients, negative antibody scintigrams were found with positive X-ray or bone scintigrams following successful therapy. The study was particularly valuable in two patients differentiating malignant disease from other causes of positive bone scintigrams or X-rays

  11. Immunomodulatory Gene Therapy Prevents Antibody Formation and Lethal Hypersensitivity Reactions in Murine Pompe Disease

    OpenAIRE

    Sun, Baodong; Kulis, Michael D; Young, Sarah P.; Hobeika, Amy C; Li, Songtao; Bird, Andrew; Zhang, Haoyue; Li, Yifan; Clay, Timothy M.; Burks, Wesley; Kishnani, Priya S.; Koeberl, Dwight D

    2009-01-01

    Infantile Pompe disease progresses to a lethal cardiomyopathy in absence of effective treatment. Enzyme-replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) has been effective in most patients with Pompe disease, but efficacy was reduced by high-titer antibody responses. Immunomodulatory gene therapy with a low dose adeno-associated virus (AAV) vector (2 × 1010 particles) containing a liver-specific regulatory cassette significantly lowered immunoglobin G (IgG), IgG1, a...

  12. Sym004, a Novel EGFR Antibody Mixture, Can Overcome Acquired Resistance to Cetuximab1

    OpenAIRE

    Iida, Mari; Brand, Toni M; Starr, Megan M.; Li, Chunrong; Huppert, Evan J; Luthar, Neha; Pedersen, Mikkel W; Horak, Ivan D.; Kragh, Michael; Wheeler, Deric L

    2013-01-01

    The epidermal growth factor receptor (EGFR) is a central regulator of tumor progression in a variety of human cancers. Cetuximab is an anti-EGFR monoclonal antibody that has been approved for head and neck and colorectal cancer treatment, but many patients treated with cetuximab don't respond or eventually acquire resistance. To determine how tumor cells acquire resistance to cetuximab, we previously developed a model of acquired resistance using the non-small cell lung cancer line NCI-H226. ...

  13. Sym004, a Novel EGFR Antibody Mixture, Can Overcome Acquired Resistance to Cetuximab

    OpenAIRE

    Mari Iida; Brand, Toni M; Starr, Megan M.; Chunrong Li; Huppert, Evan J; Neha Luthar; Pedersen, Mikkel W; Horak, Ivan D.; Michael Kragh; Wheeler, Deric L

    2013-01-01

    The epidermal growth factor receptor (EGFR) is a central regulator of tumor progression in a variety of human cancers. Cetuximab is an anti-EGFR monoclonal antibody that has been approved for head and neck and colorectal cancer treatment, but many patients treated with cetuximab don't respond or eventually acquire resistance. To determine how tumor cells acquire resistance to cetuximab, we previously developed a model of acquired resistance using the non-small cell lung cancer line NCI-H226. ...

  14. Antiphospholipid Antibodies in Lupus Nephritis.

    Science.gov (United States)

    Parodis, Ioannis; Arnaud, Laurent; Gerhardsson, Jakob; Zickert, Agneta; Sundelin, Birgitta; Malmström, Vivianne; Svenungsson, Elisabet; Gunnarsson, Iva

    2016-01-01

    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 affected by

  15. Antiphospholipid Antibodies in Lupus Nephritis.

    Directory of Open Access Journals (Sweden)

    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

  16. Structure Based Antibody-Like Peptidomimetics

    Directory of Open Access Journals (Sweden)

    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.

  17. Next generation of antibody therapy for cancer

    Institute of Scientific and Technical Information of China (English)

    Zhenping Zhu; Li Yan

    2011-01-01

    Monoclonal antibodies (mAbs) have become a major class of therapeutic agents providing effective altematives to treating various human diseases. To date, 15 mAbs have been approved by regulatory agencies in the world for clinical use in oncology indications. The selectivity and specificity, the unique pharmacokinetics, and the ability to engage and activate the host immune system differentiate these biologics from traditional small molecule anticancer drugs. mAb-basod regimens have brought clinical benefits, including improvements in overall survival, to patients with a variety of cancers. Many challenges still remain, however, to fully realize the potential of these new medicines. With our further understanding of cancer biology, mechanism of antibody action, and advancement of antibody engineering technologies, many novel antibody formats or antibody-derived molecules are emerging as promising new generation therapeutics. Carefully designed and engineered, they retain the advantage of specificity and selectivity of original antibodies, but in the meantime acquire additional special features such as improved pharmacokinetics, increased selectivity, and enhanced anticancer efficacy. Promising clinical results are being generated with these newly improved antibody-based therapeutics.

  18. Baculovirus display of functional antibody Fab fragments.

    Science.gov (United States)

    Takada, Shinya; Ogawa, Takafumi; Matsui, Kazusa; Suzuki, Tasuku; Katsuda, Tomohisa; Yamaji, Hideki

    2015-08-01

    The generation of a recombinant baculovirus that displays antibody Fab fragments on the surface was investigated. A recombinant baculovirus was engineered so that the heavy chain (Hc; Fd fragment) of a mouse Fab fragment was expressed as a fusion to the N-terminus of baculovirus gp64, while the light chain of the Fab fragment was simultaneously expressed as a secretory protein. Following infection of Sf9 insect cells with the recombinant baculovirus, the culture supernatant was analyzed by enzyme-linked immunosorbent assay using antigen-coated microplates and either an anti-mouse IgG or an anti-gp64 antibody. A relatively strong signal was obtained in each case, showing antigen-binding activity in the culture supernatant. In western blot analysis of the culture supernatant using the anti-gp64 antibody, specific protein bands were detected at an electrophoretic mobility that coincided with the molecular weight of the Hc-gp64 fusion protein as well as that of gp64. Flow cytometry using a fluorescein isothiocyanate-conjugated antibody specific to mouse IgG successfully detected the Fab fragments on the surface of the Sf9 cells. These results suggest that immunologically functional antibody Fab fragments can be displayed on the surface of baculovirus particles, and that a fluorescence-activated cell sorter with a fluorescence-labeled antigen can isolate baculoviruses displaying specific Fab fragments. This successful baculovirus display of antibody Fab fragments may offer a novel approach for the efficient selection of specific antibodies.

  19. Chemical Profiles of Microalgae with Emphasis on Lipids: Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Benemann, J. R.; Tillett, D. M.; Suen, Y.; Hubbard, J.; Tornabene, T. G.

    1986-02-01

    This final report details progress during the third year of this subcontract. The overall objective of this subcontract was two fold: to provide the analytical capability required for selecting microalgae strains with high energy contents and to develop fundamental knowledge required for optimizing the energy yield from microalgae cultures. The progress made towards these objectives during this year is detailed in this report.

  20. Studies on Purification of Methamidophos Monoclonal Antibodies and Comoarative Immunoactivity of Purified Antibodies

    Institute of Scientific and Technical Information of China (English)

    SU-QING ZHAO; YUAN-MING SUN; CHUN-YAN ZHANG; XIAO-YU HUANG; HOU-RUI ZHANG; ZHEN-YU ZHU

    2003-01-01

    Objective To purify Methamidophos (Met) monoclonal antibodies with two methods andcompare immune activity of purified antibodies. Method Caprylic acid ammonium sulphateprecipition (CAASP) method and Sepharose protein-A (SPA) affinity chromatography method wereused to purify Met monoclonal antibodies, UV spectrum scanning was used to determine proteincontent and recovery of purified antibodies, sodium dodecylsulphate polyacrylamide gelelectrophoresis (SDS-PAGE) was used to analyze the purity of purified antibodies, and enzyme-linkedimmunosorbent assay (ELISA) was used to determine immune activity of purified antibodies.Results Antibody protein content and recovery rate with CAASP method were 7.62 mg/mL and8.05% respectively, antibody protein content and recovery rate with SPA method were 6.45 mg/mLand 5.52% respectively. Purity of antibodies purified by SPA method was higher than that by CAASPmethod. The half-maximal inhibition concentration (IC50) of antibodies purified by SPA to Met was181.26 μg/mL, and the linear working range and the limit of quantification (LOD) were 2.43-3896.01μg/mL and 1.03 μg/mL, respectively. The IC50 of antibodies purified by CAASP to Met was 352.82μg/mL, and the linear working range and LOD were 10.91-11412.29 ug/mL and 3.42 μg/mL,respectively. Conclusion Antibodies purified by SPA method are better than those by CAASPmethod, and Met monoclonal antibodies purified by SPA method can be used to prepare gold-labelledtesting paper for analyzing Met residue in vegetable and drink water.

  1. Family study of pediatric patients with primary antibody deficiencies.

    Directory of Open Access Journals (Sweden)

    Nima Rezaei

    2013-12-01

    Full Text Available Common variable immunodeficiency (CVID and selective IgA deficiency (SIGAD are the most common primary antibody deficiencies. These two diseases may have coincidence in one family and SIGAD can progress to CVID which suggest common underlying genetic defects between SIGAD and CVID. This study was designed to find the prevalence of multiple cases in families of Iranian patients with CVID or SIGAD.Serum samples were collected from all available first-degree relatives of 37 patients (23 patients with CVID and 14 with SIGAD to check the levels of immunoglobulin and their subclasses and detect antibody deficiencies.First degree family members of 37 patients (106 individuals were enrolled in this study. Thirty two percent of patients had multiple cases in their families. The frequency of primary antibody deficiency in the first relatives of the patients was estimated to be one per 9 family members. Most of the patients found among family members were siblings of the primary patients. Analysis in SIGAD family members showed that IgG and IgA levels in families with multiple cases were significantly lower than family members without multiple cases (p values of 0.048 and 0.021, respectively.Rate of families with multiple cases in Iran is more than the previous studies in other countries. This rate was not affected by the consanguinity of parents (p=0.081 or immunoglobulin level of the patients. Because of higher risk for the prevalence of these disorders in those with a positive family history of immunodeficiency, family screening programs in the patients with CVID and SIGAD can be suggested to be prioritized..

  2. Immunocytochemical and Immunohistochemical Staining with Peptide Antibodies.

    Science.gov (United States)

    Friis, Tina; Pedersen, Klaus Boberg; Hougaard, David; Houen, Gunnar

    2015-01-01

    Peptide antibodies are particularly useful for immunocytochemistry (ICC) and immunohistochemistry (IHC), where antigens may denature due to fixation of tissues and cells. Peptide antibodies can be made to any defined sequence, including unknown putative proteins and posttranslationally modified sequences. Moreover, the availability of large amounts of the antigen (peptide) allows inhibition/adsorption controls, which are important in ICC/IHC, due to the many possibilities for false-positive reactions caused by immunoglobulin Fc receptors, nonspecific reactions, and cross-reactivity of primary and secondary antibodies with other antigens and endogenous immunoglobulins, respectively. Here, simple protocols for ICC and IHC are described together with recommendations for appropriate controls.

  3. Reshaping Human Antibodies: Grafting an Antilysozyme Activity

    Science.gov (United States)

    Verhoeyen, Martine; Milstein, Cesar; Winter, Greg

    1988-03-01

    The production of therapeutic human monoclonal antibodies by hybridoma technology has proved difficult, and this has prompted the ``humanizing'' of mouse monoclonal antibodies by recombinant DNA techniques. It was shown previously that the binding site for a small hapten could be grafted from the heavy-chain variable domain of a mouse antibody to that of a human myeloma protein by transplanting the hypervariable loops. It is now shown that a large binding site for a protein antigen (lysozyme) can also be transplanted from mouse to human heavy chain. The success of such constructions may be facilitated by an induced-fit mechanism.

  4. Research and Development Trends of Antibody Therapeutics%治疗性抗体药物研究与发展趋势

    Institute of Scientific and Technical Information of China (English)

    王旻

    2011-01-01

    The advent of monoclonal antibody technology actualized the research and manufacture of monoclonal antibodies. With the development of gene engineering, recombinant genetic antibody came true. With the aid of recombinant DNA technology, murine antibody could be humanized, and some synthetic or semisynthetic human antibody library or phage displayed human antibody library have been constructed. Therefore, human antibody could be obtained by screening from such libraries. Transgenic mouse is another source of human antibody. The class of therapeutic antibodies are varied from munne antibody to human - mouse chimeric antibody,1 to humanized antibody and finally human antibody. Most of the recently approved therapeutic antibodies are derived from human antibody. From the year of 1996 to 2008, 45 percent of the monoclonal antibodies in clinical trial are anti tumor antibodies, and 28 percent are for immunologic derangement. In conclusion the development of therapeutic antibodies has run into a virtuous cycle from R&D to return, which lead to a hotspot in the international pharmaceutical industries. In this article, the history, market, problem and perspective of therapeutic antibodies are highlighted.%单克隆抗体技术的问世,使研究和生产治疗性单抗药物成为现实.随着基因工程技术的发展,新型的重组抗体技术也随之而生.人们可以利用DNA重组技术对鼠源抗体进行人源化改造、构建合成或半合成抗体库及噬菌体抗体库,从中筛选获得人源抗体,甚至利用转基因小鼠直接获得人源抗体.抗体药物发展的趋势也从鼠源、人一鼠嵌合、人源化到全人源.近年获得批准的抗体药物以全人源为主.1996年至2008年间进入临床研究的人源化单克隆抗体中45%用于治疗肿瘤,28%个用于治疗免疫紊乱.抗体药物的发展进入研发、回报的良性循环,成了国际制药业争夺的焦点.文章就治疗性抗体发展的历史、现状、市场及未来展望作了简要综述.

  5. Molecular Pathways: Immune Checkpoint Antibodies and their Toxicities.

    Science.gov (United States)

    Cousin, Sophie; Italiano, Antoine

    2016-09-15

    The emergence of immune checkpoint inhibitors for solid tumor treatments represents a major oncologic advance. Since the approval of ipilimumab, a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody, for the treatment of metastatic melanoma, many drugs, especially those targeting PD-1/PD-L1, have demonstrated promising antitumor effects in many types of cancer. By reactivating the immune system, these immunotherapies have led to the development of new toxicity profiles, also called immune-related adverse events (irAE). IrAEs can involve many organ systems, and their management is radically different from that of cytotoxic drugs; irAEs require immunosuppressive treatments, such as corticoids or TNFα antibody. In addition, the occurrence of irAEs has raised significant questions. Here, we summarize progress that has been made toward answering these questions, focusing on (i) the impact of immunotherapy dose on irAE occurrence, (ii) the correlation between irAE and patient outcome, (iii) the safety of immune checkpoint inhibitors in patients already treated for autoimmune disease, and (iv) the suspected effect on tumor growth of steroids used for the management of irAEs. Clin Cancer Res; 22(18); 4550-5. ©2016 AACR.

  6. 2004 Progress Report

    International Nuclear Information System (INIS)

    Fusion research is undertaken all over the world with the objective of realising an environmentally responsible source of energy with essentially unlimited and widely distributed fuel reserves. The results of the worldwide efforts made in recent years are now embodied in ITER, the International Thermonuclear Experimental Reactor, designed to produce at least 500 MW of fusion power with a power gain of ten. ITER will test for the first time the interaction of fusion plasma physics with power station technology. In this international framework, during 2004 Fusion Technical and Scientific Unit of ENEA obtained important results in several keys areas. At the Frascati Tokamak Upgrade the lower hybrid microwave system was fully exploited to study the generation and control of the plasma current, and the electron cyclotron heating system reached full power (1.5 MW). With the simultaneous injection of the two waves, good energy confinement regimes with internal transport barriers were obtained at the highest plasma densities ever achieved. Advanced scenario regimes were also addressed in the activities of ENEA at JET. The engineering design of the IGNITOR machine was finalised, and significant progress was made in understanding the plasma physics regimes. Among the technology activities, the qualification of the deposition process of a copper liner on carbon fibre composite (CFC) hollow tiles may be mentioned as the most important achievement. This innovative pre brazed casting process is a competitive candidate for the fabrication of the CFCbased ITER divertor components. ENEA participated in the European activity for the definition and production on an industrial scale of an advanced Nb3Sn strand for the ITER superconducting central solenoid and toroidal field coils. Contributions were also made to the design of the final conductor layout and the characterisation tests. Inertial fusion studies continued along the previous lines, namely, the study of the implosion

  7. 2004 Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Batistoni, Paola; De Marco, Francesco; Pieroni, Leonardo (ed.)

    2005-07-01

    Fusion research is undertaken all over the world with the objective of realising an environmentally responsible source of energy with essentially unlimited and widely distributed fuel reserves. The results of the worldwide efforts made in recent years are now embodied in ITER, the International Thermonuclear Experimental Reactor, designed to produce at least 500 MW of fusion power with a power gain of ten. ITER will test for the first time the interaction of fusion plasma physics with power station technology. In this international framework, during 2004 Fusion Technical and Scientific Unit of ENEA obtained important results in several keys areas. At the Frascati Tokamak Upgrade the lower hybrid microwave system was fully exploited to study the generation and control of the plasma current, and the electron cyclotron heating system reached full power (1.5 MW). With the simultaneous injection of the two waves, good energy confinement regimes with internal transport barriers were obtained at the highest plasma densities ever achieved. Advanced scenario regimes were also addressed in the activities of ENEA at JET. The engineering design of the IGNITOR machine was finalised, and significant progress was made in understanding the plasma physics regimes. Among the technology activities, the qualification of the deposition process of a copper liner on carbon fibre composite (CFC) hollow tiles may be mentioned as the most important achievement. This innovative pre brazed casting process is a competitive candidate for the fabrication of the CFCbased ITER divertor components. ENEA participated in the European activity for the definition and production on an industrial scale of an advanced Nb3Sn strand for the ITER superconducting central solenoid and toroidal field coils. Contributions were also made to the design of the final conductor layout and the characterisation tests. Inertial fusion studies continued along the previous lines, namely, the study of the implosion

  8. On disciplinary fragmentation and scientific progress.

    Directory of Open Access Journals (Sweden)

    Stefano Balietti

    Full Text Available Why are some scientific disciplines, such as sociology and psychology, more fragmented into conflicting schools of thought than other fields, such as physics and biology? Furthermore, why does high fragmentation tend to coincide with limited scientific progress? We analyzed a formal model where scientists seek to identify the correct answer to a research question. Each scientist is influenced by three forces: (i signals received from the correct answer to the question; (ii peer influence; and (iii noise. We observed the emergence of different macroscopic patterns of collective exploration, and studied how the three forces affect the degree to which disciplines fall apart into divergent fragments, or so-called "schools of thought". We conducted two simulation experiments where we tested (A whether the three forces foster or hamper progress, and (B whether disciplinary fragmentation causally affects scientific progress and vice versa. We found that fragmentation critically limits scientific progress. Strikingly, there is no effect in the opposite causal direction. What is more, our results shows that at the heart of the mechanisms driving scientific progress we find (i social interactions, and (ii peer disagreement. In fact, fragmentation is increased and progress limited if the simulated scientists are open to influence only by peers with very similar views, or when within-school diversity is lost. Finally, disciplines where the scientists received strong signals from the correct answer were less fragmented and experienced faster progress. We discuss model's implications for the design of social institutions fostering interdisciplinarity and participation in science.

  9. Site Characterization Progress Report Number 21

    Energy Technology Data Exchange (ETDEWEB)

    None

    1999-09-30

    This is the 21 st progress report issued by the U.S. Department of Energy. This report provides a summary-level discussion of Yucca Mountain Site Characterization Project progress. Accomplishments this period are presented in a format that identifies important progress achieved and conveys how that progress supports the near-term objectives in the U.S. Department of Energy's schedule. Greater detail is documented in the cited references and in deliverables listed in Appendix A to this report. This document provides a discussion of recently completed and ongoing activities conducted by the Yucca Mountain Site Characterization Project during the six-month reporting period from April 1, 1999, through September 30, 1999. Some information presented herein is by necessity preliminary, because some deliverables and reports that support the discussions have not been finalized. Projected future deliverables and reports are listed in Appendix B and are noted in the text as works in progress. Appendix C lists the status of milestone reports referenced in previous progress reports commencing with Progress Report 17. A glossary of Yucca Mountain Site Characterization Project-specific terms used in this report is given in Appendix D.

  10. Radioimmunological proof of thyroglobulin antibodies in humans by the use of a double antibody method

    International Nuclear Information System (INIS)

    Thyroid antibodies, especially thyroglobulin antibodies, allow themselves to be proven with the double antibody method, in competitive radio binding assays and with the solid phase technique. These methods offer advantages relative to sensitivity and quantifiability. In this work a sensitive radioimmunoassay as a double antibody method was worked out whereby a 125 I-thyroglobulin/thyroglobulin antibody immune complex was precipitated out using anti-human immunoglobulin. The measured results from the radioimmunoassay show a good correlation with the results of the immune histological findings. A high to very high Tg antibody level occurs with autoimmune thyroiditis (80%), primary hypothyroidism (74%) and hyperthyroidism (70%). The control values with healthy people came to less than 5% specific binding. In correlation with the results of other authors this method is advantageous relative to test start and evaluation procedures. (orig.)

  11. A study of interaction between FITC- labeled antibody and optical fiber surface

    Science.gov (United States)

    Chao, K. F.; Zhang, Y. L.; Kong, X. G.; Zeng, Q. H.; Liu, R. L.; Wang, X.; Feng, L. Y.; Sun, Y. J.

    2006-01-01

    The immobilization of antibodies on solid surface has been widely studied in elucidating immunoassay and in developing immunosensor. In this paper, FITC-labeled goat anti-human IgG were covalently immobilized on 3-aminopropyltriethoxysilane (APTES) and glutaraldehyde (Glu) to modify the distal end of a fiber-optic probe. The higher density and stability of FITC-labeled goat anti-human IgG could be obtained on the fiber surface modified with APTES-Glu than that on the non-modified fiber surface by evanescent excited fluorescence spectroscopy. Furthermore, red shift of the FITC fluorescence dye emission peak was observed on different fiber surface, exhibiting different interaction between FITC- labeled antibody and surface. Finally, under these conditions antigen-antibody reaction was investigated as an immunosensor. Detection limit of the evanescent wave optic-fiber biosensor is 10ng/ml.

  12. Chemical biology: How to minimalize antibodies

    Science.gov (United States)

    Rader, Christoph

    2015-02-01

    The success of antibodies as pharmaceuticals has triggered interest in crafting much smaller mimics. A crucial step forward has been taken with the chemical synthesis of small molecules that recruit immune cells to attack cancer cells.

  13. Patient-Derived Antibody Targets Tumor Cells

    Science.gov (United States)

    An NCI Cancer Currents blog on an antibody derived from patients that killed tumor cells in cell lines of several cancer types and slowed tumor growth in mouse models of brain and lung cancer without evidence of side effects.

  14. Localization of tumors by radiolabelled antibodies

    International Nuclear Information System (INIS)

    A method of utilizing radiolabelled antibodies to carcinoembryonic antigens for determining the site of tumors which produce or are associated with carcinoembryonic antigen is disclosed. 3 claims, no drawings

  15. Quantitative Assessment of Antibody Internalization with Novel Monoclonal Antibodies against Alexa Fluorophores

    OpenAIRE

    Liao-Chan, Sindy; Daine-Matsuoka, Barbara; Heald, Nathan; Wong, Tiffany; Lin, Tracey; Cai, Allen G.; Lai, Michelle; D’Alessio, Joseph A.; Theunissen, Jan-Willem

    2015-01-01

    Antibodies against cell surface antigens may be internalized through their specific interactions with these proteins and in some cases may induce or perturb antigen internalization. The anti-cancer efficacy of antibody-drug conjugates is thought to rely on their uptake by cancer cells expressing the surface antigen. Numerous techniques, including microscopy and flow cytometry, have been used to identify antibodies with desired cellular uptake rates. To enable quantitative measurements of inte...

  16. Influenza-Specific Antibody-Dependent Phagocytosis

    OpenAIRE

    Ana-Sosa-Batiz, Fernanda; Vanderven, Hillary; Jegaskanda, Sinthujan; Johnston, Angus; Rockman, Steven; Laurie, Karen; Barr, Ian; Reading, Patrick; Lichtfuss, Marit; Stephen J Kent

    2016-01-01

    Background Immunity to human influenza A virus (IAV) infection is only partially understood. Broadly non-neutralizing antibodies may assist in reducing disease but have not been well characterized. Methods We measured internalization of opsonized, influenza protein-coated fluorescent beads and live IAV into a monocytic cell line to study antibody-dependent phagocytosis (ADP) against multiple influenza hemagglutinin (HA) subtypes. We analyzed influenza HA-specific ADP in healthy human donors, ...

  17. Single-domain antibodies for brain targeting

    OpenAIRE

    Lalatsa, Katerina; Moreira Leite, Diana

    2014-01-01

    Smaller recombinant antibody fragments as single-domain antibodies (sdAbs) are emerging as credible alternatives because of their target specificity, high affinity, and cost-effective recombinant production. sdAbs have been forged into multivalent and multispecif ic therapeutics, or targeting moieties, that are able to shuttle their linked therapeutic cargo (i.e., drugs, nanoparticles, toxins, enzymes, and radionuclides) to the receptor of interest. Their ability to permeate across the blood ...

  18. Final Technical Report

    International Nuclear Information System (INIS)

    The two main objectives of this project were: (1) to develop and test technologies to harvest, transport, store, and separate corn stover to supply a clean raw material to the bioproducts industry, and (2) engineer fermentation systems to meet performance targets for lactic acid and ethanol manufacturers. Significant progress was made in testing methods to harvest corn stover in a 'single pass' harvest mode (collect corn grain and stover at the same time). This is technically feasible on small scale, but additional equipment refinements will be needed to facilitate cost effective harvest on a larger scale. Transportation models were developed, which indicate that at a corn stover yield of 2.8 tons/acre and purchase price of $35/ton stover, it would be unprofitable to transport stover more than about 25 miles; thus suggesting the development of many regional collection centers. Therefore, collection centers should be located within about 30 miles of the farm, to keep transportation costs to an acceptable level. These collection centers could then potentially do some preprocessing (to fractionate or increase bulk density) and/or ship the biomass by rail or barge to the final customers. Wet storage of stover via ensilage was tested, but no clear economic advantages were evident. Wet storage eliminates fire risk, but increases the complexity of component separation and may result in a small loss of carbohydrate content (fermentation potential). A study of possible supplier-producer relationships, concluded that a 'quasi-vertical' integration model would be best suited for new bioproducts industries based on stover. In this model, the relationship would involve a multiyear supply contract (processor with purchase guarantees, producer group with supply guarantees). Price will likely be fixed or calculated based on some formula (possibly a cost plus). Initial quality requirements will be specified (but subject to refinement).Producers would invest in harvest

  19. Final Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Aristos Aristidou Natureworks); Robert Kean (NatureWorks); Tom Schechinger (IronHorse Farms, Mat); Stuart Birrell (Iowa State); Jill Euken (Wallace Foundation & Iowa State)

    2007-10-01

    The two main objectives of this project were: 1) to develop and test technologies to harvest, transport, store, and separate corn stover to supply a clean raw material to the bioproducts industry, and 2) engineer fermentation systems to meet performance targets for lactic acid and ethanol manufacturers. Significant progress was made in testing methods to harvest corn stover in a “single pass” harvest mode (collect corn grain and stover at the same time). This is technically feasible on small scale, but additional equipment refinements will be needed to facilitate cost effective harvest on a larger scale. Transportation models were developed, which indicate that at a corn stover yield of 2.8 tons/acre and purchase price of $35/ton stover, it would be unprofitable to transport stover more than about 25 miles; thus suggesting the development of many regional collection centers. Therefore, collection centers should be located within about 30 miles of the farm, to keep transportation costs to an acceptable level. These collection centers could then potentially do some preprocessing (to fractionate or increase bulk density) and/or ship the biomass by rail or barge to the final customers. Wet storage of stover via ensilage was tested, but no clear economic advantages were evident. Wet storage eliminates fire risk, but increases the complexity of component separation and may result in a small loss of carbohydrate content (fermentation potential). A study of possible supplier-producer relationships, concluded that a “quasi-vertical” integration model would be best suited for new bioproducts industries based on stover. In this model, the relationship would involve a multiyear supply contract (processor with purchase guarantees, producer group with supply guarantees). Price will likely be fixed or calculated based on some formula (possibly a cost plus). Initial quality requirements will be specified (but subject to refinement).Producers would invest in harvest

  20. Therapeutic monoclonal antibody for Sporotrichosis

    Directory of Open Access Journals (Sweden)

    Sandro eAlmeida

    2012-11-01

    Full Text Available Sporotrichosis is a chronic subcutaneous mycosis that affects either humans or animals and occurs worldwide. This subcutaneous mycosis had been attributed to a single etiological agent, Sporothrix schenckii. S. schenckii exhibits a considerable genetic variability, where recently, was suggesting that this taxon consists of a complex of species. Sporotrichosis is caused by traumatic inoculation of the fungus, which is a ubiquitous environmental saprophyte that can be isolated from soil and plant debris. The infection is limited to the cutaneous forms but, recently, occurrences of more severe clinical forms of this mycosis were described, especially among immunocompromized individuals. The immunological mechanisms involved in prevention and control of sporotrichosis are still not very well understood. Some works suggest that cell-mediated immunity plays an important role in protecting the host against S. schenckii. In contrast, the role of the humoral immune response in protection against this fungus have not been studied in detail. In a previous study, we showed that antigens secreted by S. schenckii induce a specific humoral response in infected animals, mainly against the 70-kDa molecules, indicating a possible participation of specific antibodies to this molecule in infection control. In an other work of the our group, we produced a mAb against a 70-kDa glycoprotein of S. schenckii in order to better understand the effect of passive immunization of mice infected with S. schenckii. Results showed a significant reduction in the number of CFU in organs of mice when the mAb was injected before and during S. schenckii infection. Similar results were observed when T-cell deficient mice were used. Drugs of choice in the treatment of sporothrichosis require long periods and frequently relapses are observed, mainly in immunocompromized patients. The strong protection induced by mAb against a 70-kDa glycoprotein makes it a strong candidate for a

  1. IMPORTANCE OF RESEARCH HLA ANTIBODIES CLASS I AND II, AND MICA ANTIBODIES IN KIDNEY TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    M. Sh. Khubutia

    2011-01-01

    Full Text Available The purpose of this study was to investigate the occurrence of HLA and MICA antibodies in patients from the waiting list for kidney transplantation and their influence on the course of post-transplant period. Determination of HLA antibodies class I and II, and MICA antibodies was performed on a platform of Luminex (xMAP-tech- nology using sets LABScreen ONE LAMBDA (U.S.. A total of 156 patients from the waiting list for kidney transplantation. Revealed the presence of HLA and MICA antibodies in the serum of 31.4% of patients. Regraf- ted patients increased the content of antibodies to the antigens of HLA system was noted in 88.2% of cases, 47% met the combination of antibodies to the I, II classes and MICA. In patients awaiting first kidney transplantation, HLA and MICA antibodies were determined in 23.7% of cases. The presence of pretransplant HLA and MICA antibodies had a significant influence on the course of post-transplant period. Patients with the presence of HLA and MICA in 50% of cases delayed graft function. Sessions of plasmapheresis can reduce the concentration of HLA and MICA antibodies on average by 61.1%. 

  2. Antibody-Conjugated Nanoparticles for Biomedical Applications

    Directory of Open Access Journals (Sweden)

    Manuel Arruebo

    2009-01-01

    Full Text Available Nanoscience and Nanotechnology have found their way into the fields of Biotechnology and Medicine. Nanoparticles by themselves offer specific physicochemical properties that they do not exhibit in bulk form, where materials show constant physical properties regardless of size. Antibodies are nanosize biological products that are part of the specific immune system. In addition to their own properties as pathogens or toxin neutralizers, as well as in the recruitment of immune elements (complement, improving phagocytosis, cytotoxicity antibody dependent by natural killer cells, etc., they could carry several elements (toxins, drugs, fluorochroms, or even nanoparticles, etc. and be used in several diagnostic procedures, or even in therapy to destroy a specific target. The conjugation of antibodies to nanoparticles can generate a product that combines the properties of both. For example, they can combine the small size of nanoparticles and their special thermal, imaging, drug carrier, or magnetic characteristics with the abilities of antibodies, such as specific and selective recognition. The hybrid product will show versatility and specificity. In this review, we analyse both antibodies and nanoparticles, focusing especially on the recent developments for antibody-conjugated nanoparticles, offering the researcher an overview of the different applications and possibilities of these hybrid carriers.

  3. Standardization of anti-DNA antibody assays.

    Science.gov (United States)

    Pisetsky, David S

    2013-07-01

    Antibodies to DNA (anti-DNA) are the serological hallmark of systemic lupus erythematosus and represent important biomarkers for clinical and research purposes. These antibodies are part of a family of antibodies to nucleosomes and bind to conserved sites widely present on DNA. While the value of anti-DNA as a biomarker is well established, the assay for these antibodies has involved a variety of DNA sources and systems to detect DNA-anti-DNA interactions. The influence of these variations on antibody detection has complicated assay standardization. As an antigen, DNA has unique features since it is a highly charged polymer that has structural heterogeneity. This heterogeneity can affect antigenicity which can vary on the basis of DNA origin, size, conformation and mobility. In addition, as a polymer, DNA can promote patterns of antibody binding based on monogamous or bivalent interaction which require an extended polynucleotide structure. Understanding the nature of DNA as an antigen can facilitate interpretation of serological tests and underpin efforts at better standardization.

  4. Quality control of antibodies for assay development.

    Science.gov (United States)

    Schumacher, Sarah; Seitz, Harald

    2016-09-25

    Antibodies are used as powerful tools in basic research, for example, in biomarker identification, and in various forms for diagnostics, for example, identification of allergies or autoimmune diseases. Due to their robustness and ease of handling, immunoassays are favourite methods for investigation of various biological or medical questions. Nevertheless in many cases, additional analyses such as mass spectrometry are used to validate or confirm the results of immunoassays. To minimize the workload and to increase confidence in immunoassays, there are urgent needs for antibodies which are both highly specific and well validated. Unfortunately many commercially available antibodies are neither well characterized nor fully tested for cross-reactivities. Adequate quality control and validation of an antibody is time-consuming and can be frustrating. Such validation needs to be performed for every assay/application. However, where an antibody validation is successful, a highly specific and stable reagent will be on hand. This article describes the validation processes of antibodies, including some often neglected factors, as well as unspecific binding to other sample compounds in a multiparameter diagnostic assay. The validation consists of different immunological methods, with important assay controls, and is performed in relation to the development of a diagnostic test. PMID:26873787

  5. Progressive fractal coding

    OpenAIRE

    Kopilovic, Ivan; Saupe, Dietmar; Hamzaoui, Raouf

    2001-01-01

    Progressive coding is an important feature of compression schemes. Wavelet coders are well suited for this purpose because the wavelet coefficients can be naturally ordered according to decreasing importance. Progressive fractal coding is feasible, but it was proposed only for hybrid fractal-wavelet schemes. We introduce a progressive fractal image coder in the spatial domain. A Lagrange optimization based on rate-distortion performance estimates determines an optimal ordering of the code bit...

  6. Anti-nuclear antibodies positive serum from systemic lupus erythematosus patients promotes cardiovascular manifestations and the presence of human antibody in the brain

    Directory of Open Access Journals (Sweden)

    Marie Kelly-Worden

    2014-01-01

    Full Text Available Background: Systemic lupus erythematosus (SLE is characterized by the presence of anti-nuclear antibodies (ANAs in the serum of patients. These antibodies may cross over into the brain resulting in the development of neuropsychiatric symptoms and result in abnormal pathology in other organs such as the heart and kidneys. Objective: The objective of this study was to determine if SLE pathology could be detected in the hearts and brains of rats injected with positive human ANA serum. Materials and Methods: Lewis rats (n = 31 were selected for this study due to documented research already performed with this strain in the investigation of serum sickness, encephalitis and autoimmune related carditis. Rats were injected once a week with either ANA positive or negative control serum or saline. Hearts were examined for initial signs of heart disease including the presence of lipid deposits, vegetation, increased ventricular thickness and a change in heart weight. Brains were examined for the presence of human antibody and necrotic lesions. Animals were observed for outward signs of neuropathy as well. Blood samples were taken in order to determine final circulating concentrations of IgG and monitor histamine levels. Results: Animals injected with ANA were significantly higher for lipid deposits in the heart and an increased ventricular thickness was noted. One animal even displayed Libman-Sacks endocarditis. Brains were positive for the presence of human IgG and diffuse internal lesions occurred in 80% of the ANA positive serum injected animals examined. Blood histamine levels were not significantly different, but actually lower than controls by the end of the experiment. Conclusion: Since human antibodies were detected in the brain, further studies will have to identify which antibody cross reactions are occurring within the brain, examine cell infiltration as well as characterize the antibodies associated with more destructive consequences such as

  7. [An autopsy case of amyotrophic lateral sclerosis with prominent muscle cramps, fasciculation, and high titer of anti-voltage gated potassium channel (VGKC) complex antibody].

    Science.gov (United States)

    Sato, Aki; Sakai, Naoko; Shinbo, Junsuke; Hashidate, Hideki; Igarashi, Shuichi; Kakita, Akiyoshi; Yamazaki, Motoyoshi

    2014-01-01

    The patient was a 55-year-old male who had prominent fasciculation and muscle cramps. Muscle weakness and atrophy of the trunk, respiratory system, and extremities gradually progressed. On the basis of these features, we diagnosed this patient as having amyotrophic lateral sclerosis (ALS), however, the upper motor neuron signs were not significant. Following the detection of the anti-voltage gated potassium channel (VGKC) complex antibody at 907.5 pM (normal VGKC complex antibody in the development of cramp-fasciculation syndrome has been speculated. In this ALS patient, the antibodies might be associated with pathomechanisms underlying the characteristic symptoms.

  8. Avian Diagnostic and Therapeutic Antibodies to Viral Emerging Pathogens

    Energy Technology Data Exchange (ETDEWEB)

    David Bradley

    2011-03-31

    During the current period the following key objectives were achieved: demonstration of high titer antibody production by geese following immunization with inactived H1N1 virus; completion of the epitope mapping of West Nile Virus-specific goose antibodies and initiation of epitope mapping of H1N1 flu-specific goose antibodies; advancement in scalable purification of goose antibodies.

  9. Detection of vibrio cholerae O1 by using cerium oxide nanowires - based immunosensor with different antibody immobilization methods

    Science.gov (United States)

    Tam, Phuong Dinh; Hoang, Nguyen Luong; Lan, Hoang; Vuong, Pham Hung; Anh, Ta Thi Nhat; Huy, Tran Quang; Thuy, Nguyen Thanh

    2016-05-01

    In this work, we evaluated the effects of different antibody immobilization strategies on the response of a CeO2-nanowires (NWs)-based immunosensor for Vibrio cholerae O1 detection. Accordingly, the changes in the electron-transfer resistance ( R et ) from before to after cells bind to an antibody-modified electrode prepared by using three different methods of antibody immobilization were determined. The values were 16.2%, 8.3%, and 6.65% for the method that utilized protein A, antibodies activated by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS), and absorption, respectively. Cyclic voltammetry confirmed that the change in the current was highest for the immunosensors prepared using protein A (11%), followed by those prepared with EDC/NHS-activated antibodies (9%), and finally, those prepared through absorption (7.5%). The order of the antibody immobilization strategies in terms of resulting immunosensor detection limit and sensitivity was as follows order: absorption (3.2 × 103 CFU/mL; 45.1 Ω/CFU·mL-1) < EDC/NHS-activated antibody (1.0 × 103 CFU/mL; 50.6 Ω/CFU·mL-1) < protein A (1.0 × 102 CFU/mL; 65.8 Ω/CFU·mL-1). Thus, we confirmed that the protein A - mediated method showed significantly high cell binding efficiencies compared to the random immobilization method.

  10. Serum and colostral antibody production in cows immunized with recombinant human tumor necrosis factor.

    Science.gov (United States)

    Burton, Randall; Kim, Skaison; Patel, Rutvij; Scola, Michele; Hartman, Deborah; Tracey, Daniel; Fox, Barbara S

    2016-06-01

    The use of hyper-immune bovine colostrum as a human therapeutic platform is an emerging technology with potential to deliver the efficacy of antibody therapeutics with the convenience and safety of oral or topical application. It is necessary to understand how the bovine immune system responds to immunization with foreign proteins, both in terms of the serum antibody response and the transfer of antigen-specific antibodies into the colostrum to enable efficient large-scale production of therapeutic antibodies. We have immunized 25 cows with recombinant human tumor necrosis factor (rhTNF) and measured the levels of rhTNF-specific antibodies in the serum and colostrum of these animals. We observed a decline of 84±9% in serum IgG1 concentrations in the final weeks of pregnancy that presumably reflects rapid transport of IgG1 into colostrum. The serum IgG2 levels remained constant, such that the serum IgG1 to IgG2 ratio was 1:20 at parturition. We observed substantial animal-to-animal variability in the levels of anti-rhTNF antibodies in both serum and colostrum samples. In particular, a subset of 4 cows had extraordinarily high colostral anti-rhTNF antibody production. Only a weak correlation was found between the peak serum anti-rhTNF activity and the colostral anti-rhTNF activity in these animals. The 4 cows with high colostral anti-rhTNF activities trended toward higher serum IgG1 loss relative to average colostral anti-rhTNF producers, but this difference was not statistically significant in this small sample. The high-anti-rhTNF-producing cows also exhibited a greater proportion of rhTNF-specific antibodies that bound to bovine IgG1- and IgG2-specific detection antibodies relative to the total anti-rhTNF immunoglobulin population. This finding suggests that the isotype distribution of the anti-rhTNF response is varied between individuals and genetic or environmental factors may increase the yield of antigen-specific colostral antibodies. PMID:27040787

  11. Detection of osteomyelitis using a Tc-99m labeled antigranulocyte antibody immunoscintigraphy

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the diagnostic accuracy of Tc-99m labeled antigranulocyte antibody immunoscintigraphy in the diagnosis of osteomyelitis and compare with the results of triphasic bone scan. The study population was 39 patients (22 male, 17 female) who had uncertain diagnoses of osteomyelitis. Fifteen patients had history of orthopedic surgery, and 5 had previous fracture. One milligram of monoclonal antibody against NCA-95 was labeled with 370 MBq of Tc-99m, injected intravenously, and 4 hour images were obtained. Triphasic bone scan images were obtained in 30 patients. The final diagnosis was confirmed by bacteriologic culture, biopsy or long term clinical follow up. Twenty one patients were confirmed to have osteomyelitis (1 acute, 20 chronic). Eighteen patients were without osteomyelitis. Antigranulocyte antibody immunoscintigraphy had a sensitivity of 71% (15/21), and a specificity of 89% (16/18), while the sensitivity and specificity of triphasic bone scan was 93% (13/14) and 38% (6/16), respectively. Antigranulocyte antibody scan showed higher specificity of 100% (11/11) in comparison with 33% (3/9) of triphasic bone scan in patients with history of orthopedic surgery or fracture. Antigranulocyte antibody immunoscintigraphy is more specific than that of triphasic bone scan and may be helpful in patients with history of surgery or fracture. However, sensitivity is lower than triphasic bone scan in the detection of chronic osteomyelitis

  12. Attenuation of Nitrogen Mustard-Induced Pulmonary Injury and Fibrosis by Anti-Tumor Necrosis Factor-α Antibody.

    Science.gov (United States)

    Malaviya, Rama; Sunil, Vasanthi R; Venosa, Alessandro; Verissimo, Vivianne L; Cervelli, Jessica A; Vayas, Kinal N; Hall, LeRoy; Laskin, Jeffrey D; Laskin, Debra L

    2015-11-01

    Nitrogen mustard (NM) is a bifunctional alkylating agent that causes acute injury to the lung that progresses to fibrosis. This is accompanied by a prominent infiltration of macrophages into the lung and upregulation of proinflammatory/profibrotic cytokines including tumor necrosis factor (TNF)α. In these studies, we analyzed the ability of anti-TNFα antibody to mitigate NM-induced lung injury, inflammation, and fibrosis. Treatment of rats with anti-TNFα antibody (15 mg/kg, iv, every 9 days) beginning 30 min after intratracheal administration of NM (0.125 mg/kg) reduced progressive histopathologic alterations in the lung including perivascular and peribronchial edema, macrophage/monocyte infiltration, interstitial thickening, bronchiolization of alveolar walls, fibrin deposition, emphysema, and fibrosis. NM-induced damage to the alveolar-epithelial barrier, measured by bronchoalveolar lavage (BAL) protein and cell content, was also reduced by anti-TNFα antibody, along with expression of the oxidative stress marker, heme oxygenase-1. Whereas the accumulation of proinflammatory/cytotoxic M1 macrophages in the lung in response to NM was suppressed by anti-TNFα antibody, anti-inflammatory/profibrotic M2 macrophages were increased or unchanged. Treatment of rats with anti-TNFα antibody also reduced NM-induced increases in expression of the profibrotic mediator, transforming growth factor-β. This was associated with a reduction in NM-induced collagen deposition in the lung. These data suggest that inhibiting TNFα may represent an efficacious approach to mitigating lung injury induced by mustards.

  13. Correlation between hsCRP and Anti-beta2GPI Antibody in Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Meiriza Djohari

    2011-08-01

    Full Text Available BACKGROUND: Several researches reported that inflammatory and immunological mechanism such as autoantibody to β2-glycoprotein I (anti β2GPI appear as related factors in initiation and progress of atherosclerosis lesion in patient with autoimmune disease. Antibody to β2GPI titers are correlated with atherosclerosis and in vitro studies showed that they enhance oxidized low density lipoprotein (ox-LDL uptake by macrophages. Immunization with auto-antigen β2GPI elicits an immune response to influence lesion progression that mostly happens in autoimmune subjects. The metabolic syndrome (MetS is combination of several metabolic disorders such as obesity, dyslipidemia, Diabetes Mellitus (DM and conditions due to inflammation and stress oxidative. The Correlation between inflammatory markers such as High sensitivity C-Reactive Protein (hsCRP and anti-β2GPI antibody in MetS needs to be further investigated. METHODS: This was an observational study with cross sectional design on subject with MetS as determined by the International Diabetes Federation (IDF 2005’s criteria. RESULTS: There was a positive and significant correlation between hsCRP and anti-β2GPI antibody in MetS group (r=0.406; p≤0.05 as compared to non-MetS group. We found that there was elevated level of anti-β2GPI antibody in hsCRP of 3-10 mg/L. CONCLUSIONS: Anti-β2GPI antibody may be elevated in subjects with MetS who have low grade of inflammation as shown by hsCRP. KEYWORDS: metabolic syndrome, inflammation, autoantigen, atherosclerosis, obesity.

  14. Red cell antibodies and low ionic strength: a study with enzyme-linked antiglobulin test.

    Science.gov (United States)

    Leikola, J; Perkins, H A

    1980-01-01

    Alloantibody uptake on red blood cells was quantified with an accurate and reproducible enzyme-linked antiglobulin test. The uptake of anti-D, anti-Fy2 and anti-JK3 was markedly accelerated by low ionic strength salt solution (LISS) with a final ionic strength of 0.05 M. Near maximum uptake occurred within ten minutes at room temperature which corresponded to 60 minutes in saline at 37 C. Papain treatment of red blood cells increased the amount of anti-D bound, and there was no difference whether or not the papain-treated cells were suspended in LISS. In contrast, the uptake of IgG anti-A and anti-Leb was not accelerated by LISS, nor did LISS increase the rate of binding of antiblogulin to IgG antibody-coated red blood cells. We suggest this may be explained by the fact that the ABH and Lewis antigens (as well as bound IgG antibodies) extend beyond the "ionic cloud" surrounding the red blood cell. Antibody binding in the presence of albumin was approximately the same as in saline; but if the albumin was first dialyzed against LISS, the reaction was markedly accelerated and the final antibody uptake somewhat higher than in LISS alone.

  15. Making Progress: The Use of Multiple Progress Reports to Enhance Advertising Students' Media Plan Term Projects

    Science.gov (United States)

    Kritz, Gary H.; Lozada, Hector R.; Long, Mary M.

    2007-01-01

    Since the AACSB mandates that students demonstrate effective oral and written communication skills, it is imperative that business professors do what is necessary to improve such skills. The authors investigate whether the use of using multiple progress reports in an Advertising class project improves the final product. The data results show that…

  16. A multi-Fc-species system for recombinant antibody production

    OpenAIRE

    Nizak Clément; Vielemeyer Ole; El Marjou Ahmed; Moutel Sandrine; Benaroch Philippe; Dübel Stefan; Perez Franck

    2009-01-01

    Abstract Background Genomic, transcriptomic and proteomic projects often suffer from a lack of functional validation creating a strong demand for specific and versatile antibodies. Antibody phage display represents an attractive approach to select rapidly in vitro the equivalent of monoclonal antibodies, like single chain Fv antibodies, in an inexpensive and animal free way. However, so far, recombinant antibodies have not managed to impose themselves as efficient alternatives to natural anti...

  17. Progression i musikundervisningen

    DEFF Research Database (Denmark)

    Dahlbæk, Annelise

    Hvad er progression? ; Musikalitetsbegrebet ; Fælles mål for musik ; Modeller som redskab ; Stemmen : sang ; Sammenspil ; Dans og bevægelse ; Lytning......Hvad er progression? ; Musikalitetsbegrebet ; Fælles mål for musik ; Modeller som redskab ; Stemmen : sang ; Sammenspil ; Dans og bevægelse ; Lytning...

  18. Natalizumab in progressive MS

    DEFF Research Database (Denmark)

    Romme Christensen, Jeppe; Ratzer, Rikke; Börnsen, Lars;

    2014-01-01

    OBJECTIVE: Natalizumab inhibits the migration of systemic immune cells to the CNS and may be beneficial in progressive multiple sclerosis (MS). The objective of the study was to examine the effects of natalizumab in progressive MS. METHODS: In an open-label phase 2A study, 24 patients with progre...

  19. White matter lesion progression

    DEFF Research Database (Denmark)

    Hofer, Edith; Cavalieri, Margherita; Bis, Joshua C;

    2016-01-01

    BACKGROUND AND PURPOSE: White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants asso...

  20. A recombinant, fully human monoclonal antibody with antitumor activity constructed from phage-displayed antibody fragments

    NARCIS (Netherlands)

    Huls, GA; Heijnen, IAFM; Cuomo, ME; Koningsberger, JC; Boel, E; de Vries, ARV; Loyson, SAJ; Helfrich, W; Henegouwen, GPV; van Meijer, M; de Kruif, J; Logtenberg, T

    1999-01-01

    A single-chain Fv antibody fragment specific for the tumor-associated Ep-CAM molecule was isolated from a semisynthetic phage display library and converted into an intact, fully human IgG1 monoclonal antibody (huMab), The purified huMab had an affinity of 5 nM and effectively mediated tumor cell kil

  1. Thermodynamics of antibody-antigen interaction revealed by mutation analysis of antibody variable regions.

    Science.gov (United States)

    Akiba, Hiroki; Tsumoto, Kouhei

    2015-07-01

    Antibodies (immunoglobulins) bind specific molecules (i.e. antigens) with high affinity and specificity. In order to understand their mechanisms of recognition, interaction analysis based on thermodynamic and kinetic parameters, as well as structure determination is crucial. In this review, we focus on mutational analysis which gives information about the role of each amino acid residue in antibody-antigen interaction. Taking anti-hen egg lysozyme antibodies and several anti-small molecule antibodies, the energetic contribution of hot-spot and non-hot-spot residues is discussed in terms of thermodynamics. Here, thermodynamics of the contribution from aromatic, charged and hydrogen bond-forming amino acids are discussed, and their different characteristics have been elucidated. The information gives fundamental understanding of the antibody-antigen interaction. Furthermore, the consequences of antibody engineering are analysed from thermodynamic viewpoints: humanization to reduce immunogenicity and rational design to improve affinity. Amino acid residues outside hot-spots in the interface play important roles in these cases, and thus thermodynamic and kinetic parameters give much information about the antigen recognition. Thermodynamic analysis of mutant antibodies thus should lead to advanced strategies to design and select antibodies with high affinity.

  2. The antibody mining toolbox: an open source tool for the rapid analysis of antibody repertoires.

    Science.gov (United States)

    D'Angelo, Sara; Glanville, Jacob; Ferrara, Fortunato; Naranjo, Leslie; Gleasner, Cheryl D; Shen, Xiaohong; Bradbury, Andrew R M; Kiss, Csaba

    2014-01-01

    In vitro selection has been an essential tool in the development of recombinant antibodies against various antigen targets. Deep sequencing has recently been gaining ground as an alternative and valuable method to analyze such antibody selections. The analysis provides a novel and extremely detailed view of selected antibody populations, and allows the identification of specific antibodies using only sequencing data, potentially eliminating the need for expensive and laborious low-throughput screening methods such as enzyme-linked immunosorbant assay. The high cost and the need for bioinformatics experts and powerful computer clusters, however, have limited the general use of deep sequencing in antibody selections. Here, we describe the AbMining ToolBox, an open source software package for the straightforward analysis of antibody libraries sequenced by the three main next generation sequencing platforms (454, Ion Torrent, MiSeq). The ToolBox is able to identify heavy chain CDR3s as effectively as more computationally intense software, and can be easily adapted to analyze other portions of antibody variable genes, as well as the selection outputs of libraries based on different scaffolds. The software runs on all common operating systems (Microsoft Windows, Mac OS X, Linux), on standard personal computers, and sequence analysis of 1-2 million reads can be accomplished in 10-15 min, a fraction of the time of competing software. Use of the ToolBox will allow the average researcher to incorporate deep sequence analysis into routine selections from antibody display libraries. PMID:24423623

  3. Passive antibody transfer in chickens to model maternal antibody after avian influenza vaccination.

    Science.gov (United States)

    Faulkner, Olivia B; Estevez, Carlos; Yu, Qingzhong; Suarez, David L

    2013-04-15

    Birds transfer maternal antibodies (MAb) to their offspring through the egg yolk where the antibody is absorbed and enters the circulatory system. Maternal antibodies provide early protection from disease, but may interfere with the vaccination efficacy in the chick. MAb are thought to interfere with vaccine antigen processing that reduces the subsequent immune response. Once MAb titers are depleted, the chick will respond to vaccination, but they are also susceptible to viral infection. This study examines the effect of MAb on seroconversion to different viral-vectored avian influenza virus (AIV) vaccines. Chicks were given passively transferred antibodies (PTA) using AIV hyperimmunized serum, and subsequently vaccinated with a fowlpox-AIV recombinant vaccine (FPr) or a Newcastle disease virus-AIV recombinant vaccine (NDVr). Our results indicate that passively transferred antibodies led to significant reduction of seroconversion and clinical protection from virulent challenge in recombinant virus vaccinated chicks thus demonstrating maternal antibody interference to vaccination. The passive antibody transfer model system provides an important tool to evaluate maternal antibody interference to vaccination. PMID:23398721

  4. Antibodies Produced in Response to Cryptococcus neoformans Pulmonary Infection in Mice Have Characteristics of Nonprotective Antibodies

    OpenAIRE

    Zaragoza, Oscar; Casadevall, Arturo

    2004-01-01

    Murine cryptocococcal pulmonary infection elicited serum immunoglobulin M (IgM) and IgG to the capsular polysaccharide, but only IgG stained yeast cells in alveoli. Both isotypes produced punctuate immunofluorescence patterns on yeast cells like those of nonprotective antibodies. The difficulties involved in associating humoral immunity with protection in murine cryptocococcal infection could reflect nonprotective antibody responses.

  5. A study on associations between antiprothrombin antibodies, antiplasminogen antibodies and thrombosis

    NARCIS (Netherlands)

    Simmelink, MJA; De Groot, PG; Derksen, RHWM

    2003-01-01

    Anti-prothrombin antibodies area frequent cause of lupus anticoagulant (LAC), a thrombotic risk factor. Prothrombin shares structural homology with plasminogen, a kringle protein with an important role in fibrinolysis. Cross-reactivity between antiprothrombin antibodies and plasminogen has been desc

  6. A high-yielding, generic fed-batch process for recombinant antibody production of GS-engineered cell lines

    DEFF Research Database (Denmark)

    Fan, Li; Zhao, Liang; Sun, Yating;

    2009-01-01

    (lactate and osmolality). The proportionalities of nutritional consumption were determined by direct analysis. And the robust, metabolically responsive feeding strategy was based on the off-line measurement of glucose. The fed-batch process was shown to perform equivalently in GS-CHO and GS-NS0 culture....... Compared to batch cultures, the fed-batch technology generated the magnitude of the increase in cell yields (5 fold) and final antibody concentrations (4-8 fold). The majority of the increase in final antibody concentration was functions of the increased cell density and the prolonged culture time....... This generic and high-yielding fed-batch process would shorten development time, and ensure process stability, thereby facilitating the manufacture of therapeutic antibodies by GS-engineered cell lines....

  7. Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice.

    Science.gov (United States)

    Murphy, Andrew J; Macdonald, Lynn E; Stevens, Sean; Karow, Margaret; Dore, Anthony T; Pobursky, Kevin; Huang, Tammy T; Poueymirou, William T; Esau, Lakeisha; Meola, Melissa; Mikulka, Warren; Krueger, Pamela; Fairhurst, Jeanette; Valenzuela, David M; Papadopoulos, Nicholas; Yancopoulos, George D

    2014-04-01

    Mice genetically engineered to be humanized for their Ig genes allow for human antibody responses within a mouse background (HumAb mice), providing a valuable platform for the generation of fully human therapeutic antibodies. Unfortunately, existing HumAb mice do not have fully functional immune systems, perhaps because of the manner in which their genetic humanization was carried out. Heretofore, HumAb mice have been generated by disrupting the endogenous mouse Ig genes and simultaneously introducing human Ig transgenes at a different and random location; KO-plus-transgenic humanization. As we describe in the companion paper, we attempted to make mice that more efficiently use human variable region segments in their humoral responses by precisely replacing 6 Mb of mouse Ig heavy and kappa light variable region germ-line gene segments with their human counterparts while leaving the mouse constant regions intact, using a unique in situ humanization approach. We reasoned the introduced human variable region gene segments would function indistinguishably in their new genetic location, whereas the retained mouse constant regions would allow for optimal interactions and selection of the resulting antibodies within the mouse environment. We show that these mice, termed VelocImmune mice because they were generated using VelociGene technology, efficiently produce human:mouse hybrid antibodies (that are rapidly convertible to fully human antibodies) and have fully functional humoral immune systems indistinguishable from those of WT mice. The efficiency of the VelocImmune approach is confirmed by the rapid progression of 10 different fully human antibodies into human clinical trials.

  8. Production and characterization of a peptide-based monoclonal antibody against CD44 variant 6.

    Science.gov (United States)

    Zarei, Saeed; Bayat, Ali Ahmad; Hadavi, Reza; Mahmoudi, Ahmad R; Tavangar, Banafsheh; Vojgani, Yasaman; Jeddi-Tehrani, Mahmood; Amirghofran, Zahra

    2015-02-01

    The gene that codes for the CD44 family members consists of 20 exons, nine of which encode the standard form of the molecule. The other exons can be inserted in various combinations into the membrane proximal region of the extracellular domain of the protein, giving rise to variant isoforms (CD44v). CD44 variants, especially the CD44v6, have been reported to regulate tumor invasion, progression, and metastasis of carcinomas. Producing a high affinity monoclonal antibody against human CD44v6 provides a powerful tool to monitor and trace CD44v6 function in different biological fluids. In this study, a synthetic peptide from CD44v6 was conjugated to keyhole limpet hemocyanin (KLH) and injected into BALB/c mice. Splenocytes from the immunized mice were fused with murine SP2/0 myeloma cells followed by selection of antibody producing hybridoma cells. After screening of hybridoma colonies by ELISA, high affinity antibodies were selected and purified by affinity chromatography. Western blot, immunocytochemistry, and flow cytometry experiments were used to characterize the antibodies. Six stable hybridoma cell lines, designated as 1H1, 1H2, 2A12, 2G11, 3H3, and 3H7, were obtained. Flow cytometry and immunocytochemistry results showed that the new monoclonal antibodies recognized CD44v6 on the cell surface. This novel panel of anti-CD44v6 antibodies has the potential for investigating the role of CD44v6 in cancer pathogenesis. PMID:25723282

  9. Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses.

    Science.gov (United States)

    Tay, Matthew Zirui; Liu, Pinghuang; Williams, LaTonya D; McRaven, Michael D; Sawant, Sheetal; Gurley, Thaddeus C; Xu, Thomas T; Dennison, S Moses; Liao, Hua-Xin; Chenine, Agnès-Laurence; Alam, S Munir; Moody, M Anthony; Hope, Thomas J; Haynes, Barton F; Tomaras, Georgia D

    2016-08-01

    Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine

  10. Platform for high-throughput antibody selection using synthetically-designed antibody libraries.

    Science.gov (United States)

    Batonick, Melissa; Holland, Erika G; Busygina, Valeria; Alderman, Dawn; Kay, Brian K; Weiner, Michael P; Kiss, Margaret M

    2016-09-25

    Synthetic humanized antibody libraries are frequently generated by random incorporation of changes at multiple positions in the antibody hypervariable regions. Although these libraries have very large theoretical diversities (>10(20)), the practical diversity that can be achieved by transformation of Escherichia coli is limited to about 10(10). To constrain the practical diversity to sequences that more closely mimic the diversity of natural human antibodies, we generated a scFv phage library using entirely pre-defined complementarity determining regions (CDR). We have used this library to select for novel antibodies against four human protein targets and demonstrate that identification of enriched sequences at each of the six CDRs in early selection rounds can be used to reconstruct a consensus antibody with selectivity for the target. PMID:26607994

  11. Antibody engineering using phage display with a coiled-coil heterodimeric Fv antibody fragment.

    Directory of Open Access Journals (Sweden)

    Xinwei Wang

    Full Text Available A Fab-like antibody binding unit, ccFv, in which a pair of heterodimeric coiled-coil domains was fused to V(H and V(L for Fv stabilization, was constructed for an anti-VEGF antibody. The anti-VEGF ccFv showed the same binding affinity as scFv but significantly improved stability and phage display level. Furthermore, phage display libraries in the ccFv format were constructed for humanization and affinity maturation of the anti-VEGF antibody. A panel of V(H frameworks and V(H-CDR3 variants, with a significant improvement in affinity and expressibility in both E. coli and yeast systems, was isolated from the ccFv phage libraries. These results demonstrate the potential application of the ccFv antibody format in antibody engineering.

  12. Cytolytic antibodies to melanocytes in vitiligo.

    Science.gov (United States)

    Cui, J; Arita, Y; Bystryn, J C

    1993-06-01

    Patients with vitiligo have been found to have circulating antibodies to pigment cells. To evaluate the functional activity of these antibodies, a highly sensitive europium release assay was used to compare complement-mediated cytolysis of human melanocytes by sera of 56 patients with vitiligo (20 with active disease, 25 with inactive disease, 11 with unidentified disease activity) and 47 control individuals. Significant melanocyte lysis was mediated by 32 (57%) of the patients with vitiligo but by only three (6%) of the control sera (p < 0.001), and by 17 (85%) of 20 patients with active vitiligo versus 11 (44%) of 25 patients with inactive disease (p < 0.025). Mean melanocyte lysis by vitiligo sera was 24% versus 6% by control sera (p < 0.0001). A subset of 12 vitiligo sera with high titers of cytolytic antibodies to melanocytes (34% mean cytolysis) reacted minimally (< 2% mean cytolysis) to a panel of control cells that included human and murine melanomas, human fibroblasts, lung carcinoma, and rhabdomyosarcoma. These findings indicate that antibodies present in patients with vitiligo have the functional ability to selectively kill melanocytes and are more common in active disease. These observations support, but do not prove, the hypothesis that vitiligo is an autoimmune disease and that anti-pigment cell antibodies have a role in inducing the disease. PMID:8496621

  13. Inhibition of Insulin Degradation by Hepatoma Cells after Microinjection of Monoclonal Antibodies to a Specific Cytosolic Protease

    Science.gov (United States)

    Shii, Kozui; Roth, Richard A.

    1986-06-01

    Four monoclonal antibodies were identified by their ability to bind to 125I-labeled insulin covalently linked to a cytosolic insulin-degrading enzyme from human erythrocytes. All four antibodies were also found to remove more than 90% of the insulin-degrading activity from erythrocyte extracts. These antibodies were shown to be directed to different sites on the enzyme by mapping studies and by their various properties. Two antibodies recognized the insulin-degrading enzyme from rat liver; one inhibited the erythrocyte enzyme directly; and two recognized the enzyme after gel electrophoresis and transfer to nitrocellulose filters. By this latter procedure and immunoprecipitation from metabolically labeled cells, the enzyme from a variety of tissues was shown to be composed of a single polypeptide chain of apparent Mr 110,000. Finally, these monoclonal antibodies were microinjected into the cytoplasm of a human hepatoma cell line to assess the contribution of this enzyme to insulin degradation in the intact cell. In five separate experiments, preloading of cells with these monoclonal antibodies resulted in an inhibition of insulin degradation of 18-54% (average 39%) and increased the amount of 125I-labeled insulin associated with the cells. In contrast, microinjection of control antibody or an extraneous monoclonal antibody had no effect on insulin degradation or on the amount of insulin associated with the cells. Moreover, the monoclonal antibodies to the insulin-degrading enzyme caused no significant inhibition of degradation of another molecule, low density lipoprotein. Thus, these results support a role for this enzyme in insulin degradation in the intact cell.

  14. Structural and functional basis for inhibition of erythrocyte invasion by antibodies that target Plasmodium falciparum EBA-175.

    Directory of Open Access Journals (Sweden)

    Edwin Chen

    Full Text Available Disrupting erythrocyte invasion by Plasmodium falciparum is an attractive approach to combat malaria. P. falciparum EBA-175 (PfEBA-175 engages the host receptor Glycophorin A (GpA during invasion and is a leading vaccine candidate. Antibodies that recognize PfEBA-175 can prevent parasite growth, although not all antibodies are inhibitory. Here, using x-ray crystallography, small-angle x-ray scattering and functional studies, we report the structural basis and mechanism for inhibition by two PfEBA-175 antibodies. Structures of each antibody in complex with the PfEBA-175 receptor binding domain reveal that the most potent inhibitory antibody, R217, engages critical GpA binding residues and the proposed dimer interface of PfEBA-175. A second weakly inhibitory antibody, R218, binds to an asparagine-rich surface loop. We show that the epitopes identified by structural studies are critical for antibody binding. Together, the structural and mapping studies reveal distinct mechanisms of action, with R217 directly preventing receptor binding while R218 allows for receptor binding. Using a direct receptor binding assay we show R217 directly blocks GpA engagement while R218 does not. Our studies elaborate on the complex interaction between PfEBA-175 and GpA and highlight new approaches to targeting the molecular mechanism of P. falciparum invasion of erythrocytes. The results suggest studies aiming to improve the efficacy of blood-stage vaccines, either by selecting single or combining multiple parasite antigens, should assess the antibody response to defined inhibitory epitopes as well as the response to the whole protein antigen. Finally, this work demonstrates the importance of identifying inhibitory-epitopes and avoiding decoy-epitopes in antibody-based therapies, vaccines and diagnostics.

  15. Comparison of bifunctional chelates for {sup 64}Cu antibody imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, Cara L.; Crisp, Sarah; Bensimon, Corinne [MDS Nordion, Vancouver, BC (Canada); Yapp, Donald T.T.; Ng, Sylvia S.W. [British Columbia Cancer Agency Research Centre, Vancouver, BC (Canada); University of British Columba, The Faculty of Pharmaceutical Sciences, Vancouver, BC (Canada); Sutherland, Brent W. [British Columbia Cancer Agency Research Centre, Vancouver, BC (Canada); Gleave, Martin [Prostate Centre at Vancouver General Hospital, Vancouver, BC (Canada); Jurek, Paul; Kiefer, Garry E. [Macrocyclics Inc., Dallas, TX (United States)

    2010-11-15

    Improved bifunctional chelates (BFCs) are needed to facilitate efficient {sup 64}Cu radiolabeling of monoclonal antibodies (mAbs) under mild conditions and to yield stable, target-specific agents. The utility of two novel BFCs, 1-Oxa-4,7,10-triazacyclododecane-5-S-(4-isothiocyanatobenzyl)-4,7,10-triacetic acid (p-SCN-Bn-Oxo-DO3A) and 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-4-S-(4-isothiocyanatobenzyl)-3,6,9-triacetic acid (p-SCN-Bn-PCTA), for mAb imaging with {sup 64}Cu were compared to the commonly used S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-tetraacetic acid (p-SCN-Bn-DOTA). The BFCs were conjugated to trastuzumab, which targets the HER2/neu receptor. {sup 64}Cu radiolabeling of the conjugates was optimized. Receptor binding was analyzed using flow cytometry and radioassays. Finally, PET imaging and biodistribution studies were done in mice bearing either HER2/neu-positive or HER2/neu-negative tumors. {sup 64}Cu-Oxo-DO3A- and PCTA-trastuzumab were prepared at room temperature in >95% radiochemical yield (RCY) in <30 min, compared to only 88% RCY after 2 h for the preparation of {sup 64}Cu-DOTA-trastuzumab under the same conditions. Cell studies confirmed that the immunoreactivity of the mAb was retained for each of the bioconjugates. In vivo studies showed that {sup 64}Cu-Oxo-DO3A- and PCTA-trastuzumab had higher uptake than the {sup 64}Cu-DOTA-trastuzumab at 24 h in HER2/neu-positive tumors, resulting in higher tumor to background ratios and better tumor images. By 40 h all three of the {sup 64}Cu-BFC-trastuzumab conjugates allowed for clear visualization of the HER2/neu-positive tumors but not the negative control tumor. The antibody conjugates of PCTA and Oxo-DO3A were shown to have superior {sup 64}Cu radiolabeling efficiency and stability compared to the analogous DOTA conjugate. In addition, {sup 64}Cu-PCTA and Oxo-DO3A antibody conjugates may facilitate earlier imaging with greater target to background ratios than

  16. Antigen-Antibody Interaction Database (AgAbDb): a compendium of antigen-antibody interactions.

    Science.gov (United States)

    Kulkarni-Kale, Urmila; Raskar-Renuse, Snehal; Natekar-Kalantre, Girija; Saxena, Smita A

    2014-01-01

    Antigen-Antibody Interaction Database (AgAbDb) is an immunoinformatics resource developed at the Bioinformatics Centre, University of Pune, and is available online at http://bioinfo.net.in/AgAbDb.htm. Antigen-antibody interactions are a special class of protein-protein interactions that are characterized by high affinity and strict specificity of antibodies towards their antigens. Several co-crystal structures of antigen-antibody complexes have been solved and are available in the Protein Data Bank (PDB). AgAbDb is a derived knowledgebase developed with an objective to compile, curate, and analyze determinants of interactions between the respective antigen-antibody molecules. AgAbDb lists not only the residues of binding sites of antigens and antibodies, but also interacting residue pairs. It also helps in the identification of interacting residues and buried residues that constitute antibody-binding sites of protein and peptide antigens. The Antigen-Antibody Interaction Finder (AAIF), a program developed in-house, is used to compile the molecular interactions, viz. van der Waals interactions, salt bridges, and hydrogen bonds. A module for curating water-mediated interactions has also been developed. In addition, various residue-level features, viz. accessible surface area, data on epitope segment, and secondary structural state of binding site residues, are also compiled. Apart from the PDB numbering, Wu-Kabat numbering and explicit definitions of complementarity-determining regions are provided for residues of antibodies. The molecular interactions can be visualized using the program Jmol. AgAbDb can be used as a benchmark dataset to validate algorithms for prediction of B-cell epitopes. It can as well be used to improve accuracy of existing algorithms and to design new algorithms. AgAbDb can also be used to design mimotopes representing antigens as well as aid in designing processes leading to humanization of antibodies. PMID:25048123

  17. Serological monitoring of antibodies for an early diagnosis ofaspergillosis in captive penguins

    OpenAIRE

    Ângela L. Cabana; Xavier, Melissa O.; Vanice Poester; Gabriel B. Klafke; Pedro L. B.Filho; Aryse Martins; Rodolfo P. S.Filho; Meireles, Mário C. A.

    2015-01-01

    Abstract: This study aimed to evaluate the efficacy of detection of anti-Aspergillus fumigatus antibodies in captive penguins by double radial agar gel immunodiffusion (AGID) for the aspergillosis diagnosis. We included 134 Magellanic penguins (Spheniscus magellanicus) in rehabilitation at the Center for Recovery of Marine Animals (CRAM / FURG). All of them were monitored by AGID weekly until its final destination (death or release), totalizing 660 serum samples studied. All animals were clin...

  18. Detection of complement activation using monoclonal antibodies against C3d

    OpenAIRE

    Thurman, Joshua M.; Kulik, Liudmila; Orth, Heather; Wong, Maria; Renner, Brandon; Sargsyan, Siranush A.; Mitchell, Lynne M.; Hourcade, Dennis E.; Hannan, Jonathan P.; Kovacs, James M.; Coughlin, Beth; Woodell, Alex S.; Pickering, Matthew C.; Rohrer, Bärbel; Holers, V. Michael

    2013-01-01

    During complement activation the C3 protein is cleaved, and C3 activation fragments are covalently fixed to tissues. Tissue-bound C3 fragments are a durable biomarker of tissue inflammation, and these fragments have been exploited as addressable binding ligands for targeted therapeutics and diagnostic agents. We have generated cross-reactive murine monoclonal antibodies against human and mouse C3d, the final C3 degradation fragment generated during complement activation. We developed 3 monocl...

  19. Progress of ITER vacuum vessel

    International Nuclear Information System (INIS)

    Highlights: ► This covers the overall status and progress of the ITER vacuum vessel activities. ► It includes design, R and D, manufacturing and approval process of the regulators. ► The baseline design was completed and now manufacturing designs are on-going. ► R and D includes ISI, dynamic test of keys and lip-seal welding/cutting technology. ► The VV suppliers produced full-scale mock-ups and started VV manufacturing. -- Abstract: Design modifications were implemented in the vacuum vessel (VV) baseline design in 2011–2012 for finalization. The modifications are mostly due to interface components, such as support rails and feedthroughs for the in-vessel coils (IVC). Manufacturing designs are being developed at the domestic agencies (DAs) based on the baseline design. The VV support design was also finalized and tests on scale mock-ups are under preparation. Design of the in-wall shielding (IWS) has progressed, considering the assembly methods and the required tolerances. Further modifications are required to be consistent with the DAs’ manufacturing designs. Dynamic tests on the inter-modular and stub keys to support the blanket modules are being performed to measure the dynamic amplification factor (DAF). An in-service inspection (ISI) plan has been developed and R and D was launched for ISI. Conceptual design of the VV instrumentation has been developed. The VV baseline design was approved by the agreed notified body (ANB) in accordance with the French Nuclear Pressure Equipment Order procedure

  20. Monoclonal antibodies against ROR1 induce apoptosis of chronic lymphocytic leukemia (CLL) cells.

    Science.gov (United States)

    Daneshmanesh, A H; Hojjat-Farsangi, M; Khan, A S; Jeddi-Tehrani, M; Akhondi, M M; Bayat, A A; Ghods, R; Mahmoudi, A-R; Hadavi, R; Österborg, A; Shokri, F; Rabbani, H; Mellstedt, H

    2012-06-01

    ROR1 is a receptor tyrosine kinase (RTK) recently identified to be overexpressed at the gene and protein levels in chronic lymphocytic leukemia (CLL). Monoclonal antibodies (MAbs) against RTKs have been successfully applied for therapy of solid tumors. We generated five MAbs against the Ig (n = 1), cysteine-rich (CRD) (n = 2) and kringle (KNG) (n = 2) domains, respectively, of the extracellular part of ROR1. All CLL patients (n = 20) expressed ROR1 on the surface of the leukemic cells. A significantly higher frequency of ROR1 expression was found in patients with progressive versus non-progressive disease, and in those with unmutated versus mutated IgVH genes. All five MAbs alone induced apoptosis in the absence of complement or added effector cells (Annexin-V and MTT, as well as cleavage of poly-(ADP ribose)-polymerase, caspase-8 and caspase-9) of CLL cells but not of normal B cells. Most effective were MAbs against CRD and KNG, significantly superior to rituximab (P < 0.005). Cross-linking of anti-ROR1 MAbs using the F(ab')(2) fragments of anti-Fc antibodies significantly augmented apoptosis. Two of the MAbs induced complement-dependent cytotoxicity (CDC) similar to that of rituximab and one anti-ROR1 MAb (KNG) (IgG1) showed killing activity by antibody-dependent cellular cytotoxicity. The identified ROR1 epitopes may provide a basis for generating human ROR1 MAbs for therapy. PMID:22289919

  1. Antibody-based biological toxin detection

    Energy Technology Data Exchange (ETDEWEB)

    Menking, D.E.; Goode, M.T. [Army Edgewood Research, Development and Engineering Center, Aberdeen Proving Ground, MD (United States)

    1995-12-01

    Fiber optic evanescent fluorosensors are under investigation in our laboratory for the study of drug-receptor interactions for detection of threat agents and antibody-antigen interactions for detection of biological toxins. In a direct competition assay, antibodies against Cholera toxin, Staphylococcus Enterotoxin B or ricin were noncovalently immobilized on quartz fibers and probed with fluorescein isothiocyanate (FITC) - labeled toxins. In the indirect competition assay, Cholera toxin or Botulinum toxoid A was immobilized onto the fiber, followed by incubation in an antiserum or partially purified anti-toxin IgG. These were then probed with FITC-anti-IgG antibodies. Unlabeled toxins competed with labeled toxins or anti-toxin IgG in a dose dependent manner and the detection of the toxins was in the nanomolar range.

  2. 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.

  3. Imaging spectrum of primary antiphospholipid antibody syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Kwon Ha; Won, Jong Jin [Wonkwang University Hospital, Iksan (Korea, Republic of); Ha, Hyun Kwon; Kim, Jung Hoon; Kim, Jeong Gon; Ki, Won Woo; Kim, Pyo Nyun; Lee, Moon Gyu; Auh, Yong Ho [Asan Medical Center, Seoul (Korea, Republic of)

    1998-04-01

    Antiphospholipid antibody syndrome is recognized as one of the most important causes of hypercoagulability. It can be clinically diagnosed if patients have experienced unexplained recurrent venous or arterial thrombosis, recurrent fetal loss, or thrombocytopenia in the presence of circulating autoantibodies to phospholipids, such as anticardiolipin antibody or lupus anticoagulant. Approximately half of all patients with this syndrome do not have associated systemic disease, and their condition is described as primary antiphospholipid antibody syndrome (PAPS). In the remainder, the syndrome is accompanied by systemic lupus erythematosus or other connective tissue diseases, and is known as secondary antiphospholipid syndrome (1). The purpose of this paper is to illustrate the systemic manifestation of PAPS, focusing on the radiological findings of CT, MR and angiography in clinically proven patients. (author). 8 refs., 10 figs.

  4. Characterization of monoclonal antibodies directed against human thyroid stimulating hormone

    International Nuclear Information System (INIS)

    Monoclonal antibodies directed against human thyroid stimulating hormone (TSH) were obtained from hybrid myelomas, following fusion of mouse NSI myeloma cells with mouse spleen cells. Ten different antibodies were obtained from 4 separate fusions. Eight antibodies were of the IgG1 subclass. Affinities of antibodies for TSH were in the range 2 x 108-5 x 1010 M-1. Five of the antibodies were specific for TSH and did not react with LH, FSH or hCG. The remaining antibodies reacted with all these hormones and were assumed to recognise their common (α) subunit. The 5 specific antibodies fell into 3 subgroups recognising distinct antigenic determinants, whereas the 5 non-specific antibodies recognised a single determinant or closely related set of sites. It is concluded that these antibodies should be valuable reagents for use in sensitive and specific two-site immunoradiometric assays. (Auth.)

  5. Anti-DNA antibodies--quintessential biomarkers of SLE.

    Science.gov (United States)

    Pisetsky, David S

    2016-02-01

    Antibodies that recognize and bind to DNA (anti-DNA antibodies) are serological hallmarks of systemic lupus erythematosus (SLE) and key markers for diagnosis and disease activity. In addition to common use in the clinic, anti-DNA antibody testing now also determines eligibility for clinical trials, raising important questions about the nature of the antibody-antigen interaction. At present, no 'gold standard' for serological assessment exists, and anti-DNA antibody binding can be measured with a variety of assay formats, which differ in the nature of the DNA substrates and in the conditions for binding and detection of antibodies. A mechanism called monogamous bivalency--in which high avidity results from simultaneous interaction of IgG Fab sites with a single polynucleotide chain--determines anti-DNA antibody binding; this mechanism might affect antibody detection in different assay formats. Although anti-DNA antibodies can promote pathogenesis by depositing in the kidney or driving cytokine production, they are not all alike, pathologically, and anti-DNA antibody expression does not necessarily correlate with active disease. Levels of anti-DNA antibodies in patients with SLE can vary over time, distinguishing anti-DNA antibodies from other pathogenic antinuclear antibodies. Elucidation of the binding specificities and the pathogenic roles of anti-DNA antibodies in SLE should enable improvements in the design of informative assays for both clinical and research purposes.

  6. The maturation of antibody technology for the HIV epidemic.

    Science.gov (United States)

    Winnall, Wendy R; Beasley, Matthew D; Center, Rob J; Parsons, Matthew S; Kiefel, Ben R; Kent, Stephen J

    2014-08-01

    Antibodies are one of our most useful biological tools. Indeed, improvements in antibody-based technologies have ushered in a new era of antibody-based therapeutics, research and diagnostic tools. Although improved technologies have led to the development of therapeutic antibodies for treatment of malignancies and inflammatory conditions, the use of advanced antibody technology in the therapy of viral infections is in its infancy. Non-human primate studies have demonstrated that antibodies against the HIV envelope can both prevent viral infection and control viremia. Despite the obvious potential of antibody therapies against HIV, there remain limitations in production and purification capacity that require further research. Recent advances in recombinant antibody technology have led to the development of a range of novel antibody fragments, such as single-domain nanobodies and bispecific antibodies, that are capable of targeting cancer cells to cytotoxic T cells. Novel antibody production techniques have also been designed, allowing antibodies to be obtained from non-mammalian cells, bovine colostrum and the periplasm and cytoplasm of bacteria. These advances may allow large-scale production of HIV antibodies that are capable of protecting against HIV infection or serving as therapeutics that reduce the need for life-long antiretroviral treatment. This review summarises recent advances in antibody-based technologies and discusses the possibilities and challenges of using these advances to design prophylactics and therapeutics against HIV. PMID:24797582

  7. Mechanistic studies of antibody mediated clearance of tau aggregates using an ex vivo brain slice model

    Directory of Open Access Journals (Sweden)

    Pavan eKrishnamurthy

    2011-10-01

    Full Text Available Recent studies have shown that immunotherapy clears amyloid beta (A plaques and reduces A levels in mouse models of Alzheimer’s disease (AD, as well as in AD patients. Tangle pathology is also relevant for the neurodegeneration in AD, and our studies have shown that active immunization with an AD related phospho-tau peptide reduces aggregated tau within the brain and slows the progression of tauopathy-induced behavioural impairments. Thus, clearance of neurofibrillary tangles and/or their precursors may reduce synaptic and neuronal loss associated with AD and other tauopathies. So far the mechanisms involved in antibody-mediated clearance of tau pathology are yet to be elucidated. In this study we have used a mouse brain slice model to examine the uptake and localization of FITC labeled anti-tau antibodies. Confocal microscopy analysis showed that the FITC labelled anti-tau antibody co-stained with phosphorylated tau, had a perinuclear appearance and co-localised with markers of the endosomal/lysosomal pathway. Additionally, tau and FITC IgG were found together in an enriched lysosome fraction. In summary, antibody-mediated clearance of intracellular tau aggregates appears to occur via the lysosomal pathway.

  8. Antibodies to new beta cell antigen ICA12 in Latvian diabetes patients.

    Science.gov (United States)

    Shtauvere-Brameus, A; Hagopian, W; Rumba, I; Sanjeevi, C B

    2002-04-01

    In Latvia diabetes mellitus is diagnosed using the WHO's clinical criteria, and assays for the detection of autoantibodies are not available. In consequence, slowly progressive autoimmune diabetes or LADA is likely to be missed. Antibodies to GAD65 and IA-2 are the major immunological markers in autoimmune diabetes. Recently, a new beta cell antigen, called ICA12, has been identified, which has a homology to the SOX family of transcription factors. The aim of the study was to analyze the prevalence of ICA12 antibodies in diabetes mellitus patients and controls from Latvia and to see whether this antigen is important in revealing autoimmunity when antibodies against major antigens are not present. We studied 88 IDDM patients and 100 NIDDM patients as well as controls for the prevalence of GAD65, IA-2, and ICA12 antibodies by radioligand binding assay (RIA) using (35)S-labeled islet antigens. We found ICA12Abs in 26 of 88 IDDM patients (30%) vs. 4% in healthy controls (4/100) and in 9 of 100 NIDDM patients (9%) vs. 2% controls (2/100). ICA12Abs alone are present in only 3% (3/88) of the patients with IDDM and 1% (1/100) of the NIDDM patients. We conclude that ICA12 represents the minor antigens in autoimmune diabetes and that, as a minor antigen, ICA12 alone does not contribute significantly in revealing new cases of autoimmunity.

  9. GSN antibody pretreatment aggravates radiation-induced lung injury in mice

    International Nuclear Information System (INIS)

    Radiation-induced lung injury is one of the main dose limiting factors for thoracic radiation therapy. Gelsolin (GSN) is a widespread, multifunctional regulator of cellular structure and metabolism. In this work, the roles of GSN in radiation-induced lung injury in Balb/c mice were studied. The GSN levels in plasma reduced progressively in 72 hours after irradiation, and then increased gradually. GSN contents in the bronchoalveolar lavage (BAL) fluid increased after thoracic irradiation, whereas mRNA levels of GSN in the lung tissue decreased significantly within 24 hours after irradiation and then increased again. Mice were intravenously injected with 50 μg GSN antibody 0.5 hour before 20 Gy of thoracic irradiation. GSN antibody pretreatment increased lung inflammation, protein concentration in the BAL fluid and leukocytes infiltration in the irradiated mice. The activities of superoxidase dismutase (SOD) in the plasma and the BAL fluid in irradiated mice injected with GSN antibody were less than that of control groups, whereas the levels of malondialdehyde (MDA) increased. These results suggest that pretreatment of GSN antibody may aggravate radiation-induced pneumonitis. (authors)

  10. Progress in plant protoplast research.

    Science.gov (United States)

    Eeckhaut, Tom; Lakshmanan, Prabhu Shankar; Deryckere, Dieter; Van Bockstaele, Erik; Van Huylenbroeck, Johan

    2013-12-01

    In this review we focus on recent progress in protoplast regeneration, symmetric and asymmetric hybridization and novel technology developments. Regeneration of new species and improved culture techniques opened new horizons for practical breeding in a number of crops. The importance of protoplast sources and embedding systems is discussed. The study of reactive oxygen species effects and DNA (de)condensation, along with thorough phytohormone monitoring, are in our opinion the most promising research topics in the further strive for rationalization of protoplast regeneration. Following, fusion and fragmentation progress is summarized. Genomic, transcriptomic and proteomic studies have led to better insights in fundamental processes such as cell wall formation, cell development and chromosome rearrangements in fusion products, whether or not obtained after irradiation. Advanced molecular screening methods of both genome and cytoplasmome facilitate efficient screening of both symmetric and asymmetric fusion products. We expect that emerging technologies as GISH, high resolution melting and next generation sequencing will pay major contributions to our insights of genome creation and stabilization, mainly after asymmetric hybridization. Finally, we demonstrate agricultural valorization of somatic hybridization through enumerating recent introgression of diverse traits in a number of commercial crops. PMID:23955146

  11. Antibody engineering & therapeutics, the annual meeting of the antibody society December 7–10, 2015, San Diego, CA, USA

    Science.gov (United States)

    Pauthner, Matthias; Yeung, Jenny; Ullman, Chris; Bakker, Joost; Wurch, Thierry; Reichert, Janice M.; Lund-Johansen, Fridtjof; Bradbury, Andrew R.M.; Carter, Paul J.; Melis, Joost P.M.

    2016-01-01

    ABSTRACT The 26th Antibody Engineering & Therapeutics meeting, the annual meeting of The Antibody Society united over 800 participants from all over the world in San Diego from 6–10 December 2015. The latest innovations and advances in antibody research and development were discussed, covering a myriad of antibody-related topics by more than 100 speakers, who were carefully selected by The Antibody Society. As a prelude, attendees could join the pre-conference training course focusing, among others, on the engineering and enhancement of antibodies and antibody-like scaffolds, bispecific antibody engineering and adaptation to generate chimeric antigen receptor constructs. The main event covered 4 d of scientific sessions that included antibody effector functions, reproducibility of research and diagnostic antibodies, new developments in antibody-drug conjugates (ADCs), preclinical and clinical ADC data, new technologies and applications for bispecific antibodies, antibody therapeutics for non-cancer and orphan indications, antibodies to harness the cellular immune system, building comprehensive IgVH-gene repertoires through discovering, confirming and cataloging new germline IgVH genes, and overcoming resistance to clinical immunotherapy. The Antibody Society's special session focused on “Antibodies to watch” in 2016. Another special session put the spotlight on the limitations of the new definitions for the assignment of antibody international nonproprietary names introduced by the World Health Organization. The convention concluded with workshops on computational antibody design and on the promise and challenges of using next-generation sequencing for antibody discovery and engineering from synthetic and in vivo libraries. PMID:26909869

  12. Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus

    Science.gov (United States)

    Wong-Baeza, Carlos; Reséndiz-Mora, Albany; Donis-Maturano, Luis; Wong-Baeza, Isabel; Zárate-Neira, Luz; Yam-Puc, Juan Carlos; Calderón-Amador, Juana; Medina, Yolanda; Wong, Carlos; Baeza, Isabel; Flores-Romo, Leopoldo

    2016-01-01

    Anti-lipid IgG antibodies are produced in some mycobacterial infections and in certain autoimmune diseases [such as anti-phospholipid syndrome, systemic lupus erythematosus (SLE)]. However, few studies have addressed the B cell responses underlying the production of these immunoglobulins. Anti-lipid IgG antibodies are consistently found in a murine model resembling human lupus induced by chlorpromazine-stabilized non-bilayer phospholipid arrangements (NPA). NPA are transitory lipid associations found in the membranes of most cells; when NPA are stabilized they can become immunogenic and induce specific IgG antibodies, which appear to be involved in the development of the mouse model of lupus. Of note, anti-NPA antibodies are also detected in patients with SLE and leprosy. We used this model of lupus to investigate in vivo the cellular mechanisms that lead to the production of anti-lipid, class-switched IgG antibodies. In this murine lupus model, we found plasma cells (Gr1−, CD19−, CD138+) producing NPA-specific IgGs in the draining lymph nodes, the spleen, and the bone marrow. We also found a significant number of germinal center B cells (IgD−, CD19+, PNA+) specific for NPA in the draining lymph nodes and the spleen, and we identified in situ the presence of NPA in these germinal centers. By contrast, very few NPA-specific, extrafollicular reaction B cells (B220+, Blimp1+) were found. Moreover, when assessing the anti-NPA IgG antibodies produced during the experimental protocol, we found that the affinity of these antibodies progressively increased over time. Altogether, our data indicate that, in this murine model resembling human lupus, B cells produce anti-NPA IgG antibodies mainly via germinal centers. PMID:27746783

  13. Changes in Antibody Levels during and following an Episode of Acute Adenolymphangitis (ADL among Lymphedema Patients in Leogane, Haiti.

    Directory of Open Access Journals (Sweden)

    Katherine E Mues

    Full Text Available Episodes of acute adenolymphangitis (ADL are often the first clinical sign of lymphatic filariasis (LF. They are often accompanied by swelling of the affected limb, inflammation, fever, and general malaise and lead to the progression of lymphedema. Although ADL episodes have been studied for a century or more, questions still remain as to their etiology. We quantified antibody levels to pathogens that potentially contribute to ADL episodes during and after an episode among lymphedema patients in Léogâne, Haiti. We estimated the proportion of ADL episodes hypothesized to be attributed to specific pathogens.We measured antibody levels to specific pathogens during and following an ADL episode among 41 lymphedema patients enrolled in a cohort study in Léogâne, Haiti. We calculated the absolute and relative changes in antibody levels between the ADL and convalescent time points. We calculated the proportion of episodes that demonstrated a two-fold increase in antibody level for several bacterial, fungal, and filarial pathogens.Our results showed the greatest proportion of two-fold changes in antibody levels for the carbohydrate antigen Streptococcus group A, followed by IgG2 responses to a soluble filarial antigen (BpG2, Streptococcal Pyrogenic Exotoxin B, and an antigen for the fungal pathogen Candida. When comparing the median antibody level during the ADL episode to the median antibody level at the convalescent time point, only the antigens for Pseudomonas species (P-value = 0.0351 and Streptolysin O (P-value = 0.0074 showed a significant result.Although our results are limited by the lack of a control group and few antibody responses, they provide some evidence for infection with Streptococcus A as a potential contributing factor to ADL episodes. Our results add to the current evidence and illustrate the importance of determining the causal role of bacterial and fungal pathogens and immunological antifilarial response in ADL episodes.

  14. Cassini's Grand Finale: The Final Orbits

    Science.gov (United States)

    Spilker, Linda; Edgington, Scott

    2016-04-01

    The Cassini-Huygens mission, a joint collaboration between NASA, ESA and the Italian Space Agency, is approaching its last year of operations after nearly 12 years in orbit around Saturn. Cassini will send back its final bits of unique data on September 15th, 2017 as it plunges into Saturn's atmosphere, vaporizing and satisfying planetary protection requirements. Before that time Cassini will continue its legacy of exploration and discovery with 12 close flybys of Titan in 2016 and 2017 that will return new science data as well as sculpt the inclinations and periods of the final orbits. Even though all of our close icy satellite flybys, including those of Enceladus, are now completed, numerous Voyager-class flybys (summer solstice approaches. In November 2016 Cassini will transition to a series of orbits with peripases just outside Saturn's F ring. These 20 orbits will include close flybys of some tiny ring moons and excellent views of the F ring and outer A ring. The 126th and final close flyby of Titan will propel Cassini across Saturn's main rings and into its final orbits. Cassini's Grand Finale, starting in April 2017, is comprised of 22 orbits at an inclination of 63 degrees. Cassini will repeatedly dive between the innermost rings and the upper atmosphere of the planet providing insights into fundamental questions unattainable during the rest of the mission. Cassini will be the first spacecraft to explore this region. These close orbits provide the highest resolution observations of both the rings and Saturn, and direct in situ sampling of the ring particles, composition, plasma, Saturn's exosphere and the innermost radiation belts. Saturn's gravitational field will be measured to unprecedented accuracy, providing information on the interior structure of the planet, winds in the outer layers of Saturn's atmosphere, and the mass distribution in the rings. Probing the magnetic field will give insight into the nature of the magnetic dynamo, telling us: why the

  15. Utility of feline coronavirus antibody tests.

    Science.gov (United States)

    Addie, Diane D; le Poder, Sophie; Burr, Paul; Decaro, Nicola; Graham, Elizabeth; Hofmann-Lehmann, Regina; Jarrett, Oswald; McDonald, Michael; Meli, Marina L

    2015-02-01

    Eight different tests for antibodies to feline coronavirus (FCoV) were evaluated for attributes that are important in situations in veterinary practice. We compared four indirect immunofluorescent antibody tests (IFAT), one enzyme-linked immunosorbent assay (ELISA) (FCoV Immunocomb; Biogal) and three rapid immunochromatographic (RIM) tests against a panel of samples designated by consensus as positive or negative. Specificity was 100% for all but the two IFATs based on transmissible gastroenteritis virus (TGEV), at 83.3% and 97.5%. The IFAT and ELISA tests were best for obtaining an antibody titre and for working in the presence of virus. The RIM tests were the best for obtaining a result quickly (10-15 mins); of these, the Speed F-Corona was the most sensitive, at 92.4%, followed by FASTest feline infectious peritonitis (FIP; 84.6%) and Anigen Rapid FCoV antibody test (64.1%). Sensitivity was 100% for the ELISA, one FCoV IFAT and one TGEV IFAT; and 98.2% for a second TGEV IFA and 96.1% for a second FCoV IFAT. All tests worked with effusions, even when only blood products were stipulated in the instruction manual. The ELISA and Anigen RIM tests were best for small quantities of sample. The most appropriate FCoV antibody test to use depends on the reason for testing: in excluding a diagnosis of FIP, sensitivity, specificity, small sample quantity, rapidity and ability to work in the presence of virus all matter. For FCoV screening, speed and sensitivity are important, and for FCoV elimination antibody titre is essential. PMID:24966245

  16. Antibodies for detecting and quantifying anticoagulant agents

    OpenAIRE

    Salvador, Juan Pablo; Marco, María Pilar

    2012-01-01

    [EN] The present invention relates to the design of haptens that are structurally related to coumarin oral anticoagulant compounds (COAC), to be used for the production of specific antibodies against said type of substances and the subsequent use thereof for the development of diagnosis tools for use in laboratories or in point-of-care (PoC) devices. In particular, the produced antibodies have been used to develop a diagnosis tool that enables the plasma levels of COAC to be quantified in pat...

  17. Basic immunology of antibody targeted radiotherapy

    International Nuclear Information System (INIS)

    Antibody targeted radiotherapy brings an important new treatment modality to Radiation oncology clinic. Radiation dose to tumor and normal tissues are determined by a complex interplay of antibody, antigen, tumor, radionuclide, and host-related factors. A basic understanding of these immunologic and physiologic factors is important to optimally utilize this therapy in the clinic. Preclinical and clinical studies need to be continued to broaden our understanding and to develop new strategies to further improve the efficacy of this promising form of targeted therapy

  18. Radiolabelling of monoclonal antibodies for radiotherapy. Thailand

    International Nuclear Information System (INIS)

    Nuclear medicine is now playing a great role not only in diagnostic application but also in therapy of cancer patients. Under the concept of targeted radiotherapy, a number of radiopharmaceuticals based on radiolabelled biomolecules had been evaluated for treatment of cancer by many investigators. Of these, monoclonal antibodies and some small specific peptides labelled with beta emitting radiometals such as Sm-153, Re-186, Re-188 or Y-90, are being introduced into clinical trials. The objective of this project is to develop laboratory procedures to label monoclonal antibodies, peptide or other proteins with beta emitting radionuclides to prepare radiopharmaceuticals for therapeutic purpose

  19. Radiolabelling of monoclonal antibodies for radiotherapy

    International Nuclear Information System (INIS)

    Nuclear medicine is now playing a great role not only in diagnostic application but also in therapy of cancer patients. Under the concept of targeted radiotherapy, a number of radiopharmaceuticals based on radiolabelled biomolecules had been evaluated for treatment of cancer by many investigators. Of these, monoclonal antibodies and some small specific peptides labelled with beta emitting radiometals such as Sm-153, Re-186, Re-188 or Y-90, are being introduced into clinical trials. The objective of this project is to develop laboratory procedures to label monoclonal antibodies, peptide or other proteins with beta emitting radionuclides to prepare radiopharmaceuticals for therapeutic purpose

  20. Strategy in Regulatory Decision-Making for Management of Progressive Multifocal Leukoencephalopathy

    NARCIS (Netherlands)

    Segec, A; Keller-Stanislawski, B; Vermeer, N S; Macchiarulo, C; Straus, S M; Hidalgo-Simon, A; De Bruin, M L

    2015-01-01

    Progressive multifocal leukoencephalopathy (PML) has been observed after the use of several medicines, including monoclonal antibodies. As these drugs play important roles in the therapeutic armamentarium, it is important to address the challenges that this severe adverse reaction poses to the safe

  1. Strategy in Regulatory Decision-Making for Management of Progressive Multifocal Leukoencephalopathy

    DEFF Research Database (Denmark)

    Segec, A; Keller-Stanislawski, B; Vermeer, N S;

    2015-01-01

    Progressive multifocal leukoencephalopathy (PML) has been observed after the use of several medicines, including monoclonal antibodies. As these drugs play important roles in the therapeutic armamentarium, it is important to address the challenges that this severe adverse reaction poses to the sa...

  2. Progressive Supranuclear Palsy

    Science.gov (United States)

    Progressive supranuclear palsy (PSP) is a rare brain disease. It affects brain cells that control the movement of your eyes. This leads to ... speech, vision and swallowing problems. Doctors sometimes confuse PSP with Parkinson's disease or Alzheimer's disease. PSP has ...

  3. Physicians’ Progress Notes

    DEFF Research Database (Denmark)

    Bansler, Jørgen; Havn, Erling C.; Mønsted, Troels;

    2013-01-01

    This paper examines physicians’ progress notes, an artifact that, in spite of its obvious importance in the coordination of cooperative work in clinical settings, has not been subjected to systematic study under CSCW auspices. While several studies have addressed the role of the medical record...... in patient care, they have not dealt specifically with the role, structure, and content of the progress notes. As a consequence, CSCW research has not yet taken fully into account the fact that progress notes are coordinative artifacts of a rather special kind, an open-ended chain of prose texts, written...... sequentially by cooperating physicians for their own use as well as for that of their colleagues. We argue that progress notes are the core of the medical record, in that they marshal and summarize the overwhelming amount of data that is available in the modern hospital environment, and that their narrative...

  4. Progress for the Paralyzed

    Science.gov (United States)

    ... this page please turn Javascript on. Feature: NIBIB Robotics Progress for the Paralyzed Past Issues / Spring 2013 ... Paralyzed —The expanding options for paralyzed individuals include: robotic arms spinal cord stimulation improved prosthetic limbs restored ...

  5. Progress report for '89

    International Nuclear Information System (INIS)

    The 1989 Progress Report presents the most important scientific and technical achievements of the Nuclear Research Institute's research work. Some specialized products prepared at or fabricated by the NRI are mentioned as well. (author). 24 figs., 8 tabs., 101 refs

  6. Progress report, Physics Division

    International Nuclear Information System (INIS)

    This report reviews events and progress in the following areas: development of the TASCC facility; experimental and theoretical nuclear physics research; radionuclide standardization; condensed matter research; applied mathematics; and computer facility operation

  7. Progress report 1985

    International Nuclear Information System (INIS)

    This progress report of the nuclear physics institute includes five basic subjects: theoretical physics, high energy and intermediate energy physics, nuclear physics, combined research physics and instrumentation (microelectronics, imaging, multidetectors, scintillators,...)

  8. Comparison of spectacle classical progressive and office progressive lenses.

    Science.gov (United States)

    Kozlík, Marek; Knollová, Libuse Nováková

    2013-04-01

    This paper elaborates on analysis of progressive spectacle lenses, to correct presbyopia, which are nowadays offered at the market. The paper describes different types of progressive lenses, their parameters, length and width of their progressive segments. It also describes degressive spectacles lenses--progressive lenses on middle and near distance. The main part of the paper is a comparison of functional differences among different types of progressive spectacles lenses. The paper also addresses correctness of choice of progressive lenses for different works and professions. Lastly, it elaborates on differences of centration of different types of progressive lenses and parameters for correct choice of glasses frame for progressive spectacles lenses. PMID:23837232

  9. Modeling single cell antibody excretion on a biosensor.

    Science.gov (United States)

    Stojanović, Ivan; Baumgartner, Wolfgang; van der Velden, Thomas J G; Terstappen, Leon W M M; Schasfoort, Richard B M

    2016-07-01

    We simulated, using Comsol Multiphysics, the excretion of antibodies by single hybridoma cells and their subsequent binding on a surface plasmon resonance imaging (SPRi) sensor. The purpose was to confirm that SPRi is suitable to accurately quantify antibody (anti-EpCAM) excretion. The model showed that antibody loss by diffusion away from the sensor was less than 1%. Unexpectedly, more than 99% of the excreted antibodies were captured on the sensor. These data prove the remarkable phenomenon that the SPRi output of cellular antibody excretion and its subsequent binding, performed under the conditions described here, is directly usable for quantification of single cell antibody production rates. PMID:27040182

  10. Antibody-mediated immune suppression is improved when blends of anti-RBC monoclonal antibodies are used in mice.

    Science.gov (United States)

    Bernardo, Lidice; Amash, Alaa; Marjoram, Danielle; Lazarus, Alan H

    2016-08-25

    Although the prevention of hemolytic disease of the fetus and newborn is highly effective using polyclonal anti-D, a recombinant alternative is long overdue. Unfortunately, anti-D monoclonal antibodies have been, at best, disappointing. To determine the primary attribute defining an optimal antibody, we assessed suppression of murine red blood cell (RBC) immunization by single-monoclonal antibodies vs defined blends of subtype-matched antibodies. Allogeneic RBCs expressing the HOD antigen (hen egg lysozyme [HEL]-ovalbumin-human transmembrane Duffy(b)) were transfused into naïve mice alone or together with selected combinations of HEL-specific antibodies, and the resulting suppressive effect was assessed by evaluating the antibody response. Polyclonal HEL antibodies dramatically inhibited the antibody response to the HOD antigen, whereas single-monoclonal HEL antibodies were less effective despite the use of saturating doses. A blend of monoclonal HEL-specific antibodies reactive with different HEL epitopes significantly increased the suppressive effect, whereas a blend of monoclonal antibodies that block each other's binding to the HEL protein did not increase suppression. In conclusion, these data show that polyclonal antibodies are superior to monoclonal antibodies at suppressing the immune response to the HOD cells, a feature that can be completely recapitulated using monoclonal antibodies to different epitopes. PMID:27330002

  11. Treatment of leukemia with radiolabeled monoclonal antibodies.

    Science.gov (United States)

    Sgouros, G; Scheinberg, D A

    1993-01-01

    In contrast to radioimmunotherapy of solid disease, wherein the primary obstacle to success is access of radiolabeled antibody to antigen-positive cells, in the treatment of leukemia delivering a lethal absorbed dose to the isolated cell appears to be the primary obstacle. The isolated cell is defined as one that is exposed only to self-irradiation (from internalized or surface-bound radiolabeled antibody) and to irradiation from free antibody in the blood. It is isolated in the sense that the particulate (beta, electron, alpha) emissions from its nearest neighboring antigen-positive cell do not contribute to its absorbed dose. Disease in the bone marrow and other tissues, since it is confined to a smaller volume, is more easily eradicated because the absorbed dose to a given cell nucleus is enhanced by emissions from adjacent cells (a smaller fraction of the emission energy is 'wasted'). The optimization simulations presented above for the M195 antibody suggest that the optimum dose of antibody that should be administered is that required to yield a concentration within the distribution volume of the antibody that is approximately equal to the concentration of antigen sites as determined by the tumor burden. Although not specifically considered in the modeling example presented above, antibody internalization and catabolism may be expected to play an important role in radioimmunotherapy treatment planning of leukemia. Depending upon the kinetics of internalization and catabolism, the absorbed dose to the red marrow and to antigen-positive cells may be reduced considerably, since catabolism, assuming that it is followed by rapid extrusion of the radioactive label, would decrease the cells' exposure time considerably. The recently demonstrated effectiveness of radioimmunotherapy in certain cases of B-cell lymphoma and in reducing tumor burden in acute myelogenous leukemia suggests that radioimmunotherapy is beginning to fulfill the promise held when it was initially

  12. CD47 blockade inhibits tumor progression human osteosarcoma in xenograft models

    Science.gov (United States)

    Zhang, Shui-Jun; Zhao, Chen; Qiu, Bin-Song; Gu, Hai-Feng; Hong, Jian-Fei; Cao, Li; Chen, Yu; Xia, Bing; Bi, Qin; Wang, Ya-Ping

    2015-01-01

    Osteosarcoma is the most common bone tumors in children and adolescents. Despite intensive chemotherapy, patients with advanced disease still have a poor prognosis, illustrating the need for alternative therapies. In this study, we explored the use of antibodies that block CD47 with a tumor growth suppressive effect on osteosarcoma. We first found that up-regulation of CD47 mRNA levels in the tumorous tissues from eight patients with osteosarcoma when compared with that in adjacent non-tumorous tissues. Further western-blot (WB) and immunohistochemistry (IHC) demonstrated that CD47 protein level was highly expressed in osteosarcoma compared to normal osteoblastic cells and adjacent non-tumorous tissues. Osteosarcoma cancer stem cell markers staining shown that the majority of CD44+ cells expressed CD47 albeit with different percentages (ranging from 80% to 99%). Furthermore, high CD47 mRNA expression levels were associated with a decreased probability of progression-free and overall survival. In addition, blockade of CD47 by specific Abs suppresses the invasive ability of osteosarcoma tumor cells and further inhibits spontaneous pulmonary metastasis of KRIB osteosarcoma cells in vivo. Finally, CD47 blockade increases macrophage phagocytosis of osteosarcoma tumor cells. In conclusion, our findings demonstrate that CD47 is a critical regulator in the metastasis of osteosarcoma and suggest that targeted inhibition of this antigen by anti-CD47 may be a novel immunotherapeutic approach in the management of this tumor. PMID:26093091

  13. [Progressive visual agnosia].

    Science.gov (United States)

    Sugimoto, Azusa; Futamura, Akinori; Kawamura, Mitsuru

    2011-10-01

    Progressive visual agnosia was discovered in the 20th century following the discovery of classical non-progressive visual agnosia. In contrast to the classical type, which is caused by cerebral vascular disease or traumatic injury, progressive visual agnosia is a symptom of neurological degeneration. The condition of progressive visual loss, including visual agnosia, and posterior cerebral atrophy was named posterior cortical atrophy (PCA) by Benson et al. (1988). Progressive visual agnosia is also observed in semantic dementia (SD) and other degenerative diseases, but there is a difference in the subtype of visual agnosia associated with these diseases. Lissauer (1890) classified visual agnosia into apperceptive and associative types, and it in most cases, PCA is associated with the apperceptive type. However, SD patients exhibit symptoms of associative visual agnosia before changing to those of semantic memory disorder. Insights into progressive visual agnosia have helped us understand the visual system and discover how we "perceive" the outer world neuronally, with regard to consciousness. Although PCA is a type of atypical dementia, its diagnosis is important to enable patients to live better lives with appropriate functional support.

  14. Partial overlap of anti-mycobacterial, and anti-Saccharomyces cerevisiae mannan antibodies in Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Stefan Müller; Thomas Schaffer; Alain M Schoepfer; Annamarie Hilty; Thomas Bodmer; Frank Seibold

    2008-01-01

    AIM: To test whether humoral immune reaction against mycobacteria may play a role in anti-Saccharomyces cerevisiae antibodies (ASCA) generation in Crohn's disease (CD) and/or whether it correlates with clinical subtypes.METHODS: The dominant ASCA epitope was detected by Galanthus nivalis lectin (GNL)-binding assay. ASCA and IgG against mycobacterial lysates (M avium, M smegmatis, M chelonae, M bovis BCG, M avium ssp. paratuberculosis (MAP)] or purified lipoarabinomannans (LAM) were detected by ELISA. ASCA and anti-mycobacterial antibodies were affinity purified to assess cross-reactivities. Anti-mycobacterial IgG were induced by BCG-infection of mice.RESULTS: GNL bound to different extents to mycobacterial lysates, abundantly to purified mannose-capped (Man) I_AM from M tuberculosis, but not to uncapped LAM from M smegmatis. Fifteen to 45% of CD patients but only 0%-6% of controls were seropositive against different mycobacterial antigens. Anti-mycobacterial IgG correlated with ASCA (r=0.37-0.64; P=0.003-P<0.001). ASCA-positivity and deficiency for mannan-binding lectin synergistically associated with anti-mycobacterial IgG. In some patients, anti-mycobacterial antibodies represent cross-reactive ASCA. Vice-versa, the predominant fraction of ASCA did not cross-react with mycobacteria. Finally, fistulizing disease associated with antibodies against M avium, M smegmatis and MAP (P=0.024,0.004 and 0.045, respectively).CONCLUSION: Similar to ASCA, seroreactivity against mycobacteria may define CD patients with complicated disease and a predisposition for immune responses against ubiquitous antigens. While in some patients anti-mycobacterial antibodies strongly cross-react with yeast mannan; these cross-reactive antibodies only represent a minor fraction of total ASCA. Thus, mycobacterial infection unlikely plays a role in ASCA induction.

  15. Naturally-occurring antisperm antibodies in men: interference with fertility and implications for treatment.

    Science.gov (United States)

    Francavilla, F; Romano, R; Santucci, R; La Verghetta, G; D'Abrizio, P; Francavilla, S

    1999-02-01

    Naturally-occurring antisperm antibodies in men are a relative cause of infertility, being the fertility impairment related with the degree of sperm autoimmunization. The impairment of sperm penetration through the cervical mucus represents the best established mechanism of the antibody interference with fertility. Another mechanism may involve complement-mediated sperm injury and opsonizing effect through the female genital tract. Finally, sperm-bound antibodies can interfere with sperm functions involved in the fertilization process, mainly in the sperm-zona pellucida interaction. While some mechanisms of the antibody-interference with fertility depend only on the degree of sperm autoimmunization (e.g., inhibition of cervical mucus penetration), other mechanisms (e.g., interference with gametes interaction) could or could not occur depending on the relevance in the fertilization process of the specific antigen(s) recognized by antisperm antibodies, which are policlonal in nature. Intrauterine insemination is an effective treatment when sperm autoimmunization is low or moderate, mainly if combined with corticosteroid treatment and superovulated cycles. On the contrary, its effectiveness in cases of high degree of sperm autoimmunization is controversial. The resort to "high tech" procedures is mandatory when other less invasive approaches have failed or they may also be chosen as a first-choice method in cases of high degree of sperm autoimmunization. Since in most reports the fertilization rate with in vitro fertilization and embryo transfer (IVF-ET) was significantly lower in the presence of sperm-bound antibodies than in the case of other indications, the likelihood of fertilization is higher with intracytoplasmatic sperm injection (ICSI), where the reported fertilization rates are similar to those in other indications, or even higher. PMID:9924142

  16. A novel method for in Situ detection of hydrolyzable casein fragments in a cheese matrix by antibody phage display technique and CLSM

    DEFF Research Database (Denmark)

    Duan, Zhi; Brüggemann, Dagmar Adeline; Siegumfeldt, Henrik

    2009-01-01

    A novel method to monitor in situ hydrolyzable casein fragments during cheese ripening by using immunofluorescent labeling and confocal laser scanning microscopy (CLSM) was developed. Monoclonal single chain variable fragments of antibody (scFvs) were generated by antibody phage display toward...... three small synthetic peptides of the alpha(s1)-casein sequence. These peptides traverse enzymatic cleavage sites of casein during cheese ripening. The specificity of the generated anti-peptide antibodies was determined by ELISA and Western blot. Finally, an immunofluorescent labeling protocol...

  17. Anti Rh Hemolytic Disease due to Anti C Antibody: Is Testing for Anti D Antibodies Enough?

    OpenAIRE

    Negi, Gita; Singh, Gaur Dushyant

    2011-01-01

    Rh blood group system is a complex blood group system. Rh antibodies are produced in Rh negative individuals following exposure to foreign RBCs after transfusion or pregnancy. Anti C is a rare cause of hemolytic disease of newborn and is very scarcely reported in the literature. The aim of the present case report of Hemolytic disease caused by Anti C antibody is to bring out the fact that antibodies other than anti D should be considered in cases that give a suggestive history but no evidence...

  18. Cautionary notes on the use of NF-κB p65 and p50 antibodies for CNS studies

    Directory of Open Access Journals (Sweden)

    Listwak Samuel J

    2011-10-01

    Full Text Available Abstract Background The characterization and cellular localization of transcription factors like NF-κB requires the use of antibodies for western blots and immunohistochemistry. However, if target protein levels are low and the antibodies not well characterized, false positive data can result. In studies of NF-κB activity in the CNS, antibodies detecting NF-κB proteins have been used to support the finding that NF-κB is constitutively active in neurons, and activity levels are further increased by neurotoxic treatments, glutamate stimulation, or elevated synaptic activity. The specificity of the antibodies used was analyzed in this study. Methods Selectivity and nonselectivity of commonly used commercial and non-commercial p50 and p65 antibodies were demonstrated in western blot assays conducted in tissues from mutant gene knockout mice lacking the target proteins. Results A few antibodies for p50 and p65 each mark a single band at the appropriate molecular weight in gels containing proteins from wildtype tissue, and this band is absent in proteins from knockout tissues. Several antibodies mark proteins that are present in knockout tissues, indicating that they are nonspecific. These include antibodies raised against the peptide sequence containing the nuclear localization signals of p65 (MAB3026; Chemicon and p50 (sc-114; Santa Cruz. Some antibodies that recognize target proteins at the correct molecular weight still fail in western blot analysis because they also mark additional proteins and inconsistently so. We show that the criterion for validation by use of blocking peptides can still fail the test of specificity, as demonstrated for several antibodies raised against p65 phosphorylated at serine 276. Finally, even antibodies that show specificity in western blots produce nonspecific neuronal staining by immunohistochemistry. Conclusions We note that many of the findings in the literature about neuronal NF-κB are based on data garnered

  19. The effect of trypsin and chymotrypsin on the bactericidal activity and specific antibody activity of bovine colostrum.

    Science.gov (United States)

    Brock, J H; Arzabe, R; Piñeiro, A; Olivito, A M

    1977-01-01

    Digestion of bovine colostral whey with trypsin or chymotrypsin caused a progressive loss of the complement-mediated bactericidal activity of naturally-occurring colostral antibodies of E. coli 0111. Bactericidal activity was associated primarily with IgG1 immunoglobulin and to a lesser extent with IgM. Chymotrypsin preferentially attacked IgM, destroying its antibacterial activity and producing an apparent decrease in its mol wt. Trypsin preferentially attacked IgG1, but loss of antibacterial activity was in this case not accompanied by a decrease in molecular weight. Using colostral whey with antiperoxidase activity it was shown that the kinetics of loss of specific antibody activity were similar to those of loss of bactericidal activity. It is therefore suggested that trypsin may cause a loss of specific antibody activity of colostral IgG1 without cleaving the immunoglobulin molecule. PMID:321342

  20. Phase Transitions in Antibody Solutions: from Pharmaceuticals to Human Disease

    Science.gov (United States)

    Wang, Ying; Lomakin, Aleksey; Benedek, George; Dana Farber Cancer Institute Collaboration; Amgen Inc. Collaboration

    2014-03-01

    Antibodies are very important proteins. Natural antibodies play essential role in the immune system of human body. Pharmaceutical antibodies are used as drugs. Antibodies are also indispensable tools in biomedical research and diagnostics. Recently, a number of observations of phase transitions of pharmaceutical antibodies have been reported. These phase transitions are undesirable from the perspective of colloid stability of drug solutions in processing and storage, but can be used for protein purification, X-ray crystallography, and improving pharmokinetics of drugs. Phase transitions of antibodies can also take place in human body, particularly in multiple myeloma patients who overproduce monoclonal antibodies. These antibodies, in some cases, crystallize at body temperature and cause severe complications called cryoglobulinemia. I will present the results of our current studies on phase transitions of both pharmaceutical antibodies and cryoglobulinemia-associated antibodies. These studies have shown that different antibodies have different propensity to undergo phase transitions, but their phase behavior has universal features which are remarkably different from those of spherical proteins. I will discuss how studies of phase behavior can be useful in assessing colloid stability of pharmaceutical antibodies and in early diagnostics of cryoglobulinemia, as well as general implications of the fact that some antibodies can precipitate at physiological conditions.