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Sample records for anti-igg c3d polyspecific

  1. The complement fragment C3d facilitates phagocytosis by monocytes.

    Science.gov (United States)

    Gaither, T A; Vargas, I; Inada, S; Frank, M M

    1987-11-01

    Two receptors for fragments of C3 are described for human monocytes: CR1 and CR3, which bind C3b and iC3b, respectively. Recently a leucocyte receptor that binds C3dg has also been described, designated CR4. We previously reported that IgM-sensitized sheep erythrocytes that are heavily coated with C3d (EAC3d) can bind to human monocytes that have been cultured in fetal calf serum (FCS). Here we determine whether such binding of C3d-coated targets can lead to phagocytosis, and identify the specific monocyte receptor involved in C3d binding. We confirm that EAC3d bearing greater than 10,000 C3d/cell bind to FCS-cultured monocytes. Furthermore, using non-cultured monocytes, we demonstrate that C3d enhances rosette formation of IgG-coated E and, like C3b and iC3b, C3d augments IgG Fc receptor-mediated phagocytosis. Less than 100 C3d/cell are capable of enhancing phagocytosis, whereas 10,000 or more C3d/cell are required for rosette formation with cultured cells. These results indicate that the C3d-binding receptor is present on peripheral blood monocytes but has poor affinity for target particles coated only with C3d. Anti-CR2 monoclonal antibodies, which recognize the C3d receptor of lymphocytes, do not block EAC3d rosette formation with monocytes. In contrast anti-Mol, a monoclonal antibody against CR3, inhibits EAC3d rosettes by approximately 42%. Anti-CR1 increases this effect, but complete inhibition is not achieved. Ethylenediamine tetraacetate also markedly reduces EAC3d rosetting, reducing the numbers to less than 5%. Thus, the C3d-binding receptor on monocytes, unlike CR4, is metal dependent. Together these data indicate that CR3 is predominantly responsible for C3d binding to monocytes. PMID:3499379

  2. Electrostatic Steering Accelerates C3d:CR2 Association.

    Science.gov (United States)

    Mohan, Rohith R; Huber, Gary A; Morikis, Dimitrios

    2016-08-25

    Electrostatic effects are ubiquitous in protein interactions and are found to be pervasive in the complement system as well. The interaction between complement fragment C3d and complement receptor 2 (CR2) has evolved to become a link between innate and adaptive immunity. Electrostatic interactions have been suggested to be the driving factor for the association of the C3d:CR2 complex. In this study, we investigate the effects of ionic strength and mutagenesis on the association of C3d:CR2 through Brownian dynamics simulations. We demonstrate that the formation of the C3d:CR2 complex is ionic strength-dependent, suggesting the presence of long-range electrostatic steering that accelerates the complex formation. Electrostatic steering occurs through the interaction of an acidic surface patch in C3d and the positively charged CR2 and is supported by the effects of mutations within the acidic patch of C3d that slow or diminish association. Our data are in agreement with previous experimental mutagenesis and binding studies and computational studies. Although the C3d acidic patch may be locally destabilizing because of unfavorable Coulombic interactions of like charges, it contributes to the acceleration of association. Therefore, acceleration of function through electrostatic steering takes precedence to stability. The site of interaction between C3d and CR2 has been the target for delivery of CR2-bound nanoparticle, antibody, and small molecule biomarkers, as well as potential therapeutics. A detailed knowledge of the physicochemical basis of C3d:CR2 association may be necessary to accelerate biomarker and drug discovery efforts. PMID:27092816

  3. C3 degradation products (C3d) in normal pregnancy.

    OpenAIRE

    Jenkins, J. S.; Powell, R.J.

    1987-01-01

    Plasma C3 degradation products (C3d) were measured in 65 normal pregnancies and compared with those of non-pregnant women. No significant difference was detected between the two groups, although a difference had been previously reported. Plasma C3d estimations give an indication of complement activation and may be used as an indicator of disease activity in patients with systemic lupus erythematosus (SLE), irrespective of pregnancy.

  4. Interstellar detection of c-C3D2

    CERN Document Server

    Spezzano, S; Schilke, P; Caselli, P; Menten, K M; McCarthy, M C; Bizzocchi, L; Trevino-Morales, S P; Aikawa, Y; Schlemmer, S

    2013-01-01

    We report the first interstellar detection of c-C3D2. The doubly deuterated cyclopropenylidene, a carbene, has been detected toward the starless cores TMC- 1C and L1544 using the IRAM 30m telescope. The J(Ka,Kc) = 3(0,3)-2(1,2), 3(1,3)-2(0,2), and 2(2,1)-1(1,0) transitions of this species have been observed at 3 mm in both sources. The expected 1:2 intensity ratio has been found in the 3(0,3)-2(1,2) and 3(1,3)-2(0,2) lines, belonging to the para and ortho species respectively. We also observed lines of the main species, c-C3H2, the singly deuterated c-C3HD, and the species with one 13C off of the principal axis of the molecule, c-H13CC2H. The lines of c-C3D2 have been observed with high signal to noise ratio, better than 7.5 sigma in TMC-1C and 9 sigma in L1544. The abundance of doubly deuterated cyclopropenylidene with respect to the normal species is found to be (0.4 - 0.8)% in TMC-1C and (1.2 - 2.1)% in L1544. The deuteration of this small hydrocarbon ring is analysed with a comprehensive gas-grain model, ...

  5. Mapping of the C3d receptor (CR2)-binding site and a neoantigenic site in the C3d domain of the third component of complement.

    OpenAIRE

    LAMBRIS, J. D.; Ganu, V S; Hirani, S.; Müller-Eberhard, H. J.

    1985-01-01

    The C3d domain of C3 contains the site that binds to the C3d receptor (CR2) which is expressed on B lymphocytes. It also contains a neoantigenic determinant that is recognized by monoclonal antibody (mAb) 130 and is expressed when C3b is cleaved to iC3b and subsequently to C3dg or C3d. mAb 130 inhibits the binding of C3d to CR2. In this study, the locations of the CR2-binding site and of the neoantigen recognized by mAb 130 within the C3d domain were investigated. Treatment of human C3d with ...

  6. Disaster Prevention Coastal Map Production by MMS & C3D

    Science.gov (United States)

    Hatake, Shuhei; Kohori, Yuki; Watanabe, Yasushi

    2016-06-01

    In March 2011, Eastern Japan suffered serious damage of Tsunami caused by a massive earthquake. In 2012, Ministry of Land, Infrastructure and Transport published "Guideline of setting assumed areas of inundation by Tsunami" to establish the conditions of topography data used for simulation of Tsunami. In this guideline, the elevation data prepared by Geographical Survey Institute of Japan and 2m/5m/10m mesh data of NSDI are adopted for land area, while 500m mesh data of Hydrographic and Oceanographic Department of Japan Coast Guard and sea charts are adopted for water area. These data, however, do not have continuity between land area and water area. Therefore, in order to study the possibility of providing information for coastal disaster prevention, we have developed an efficient method to acquire continuous topography over land and water including tidal zone. Land area data are collected by Mobile Mapping System (MMS) and water area depth data are collected by interferometry echo sounder (C3D), and both data are simultaneously acquired on a same boat. Elaborate point cloud data of 1m or smaller are expected to be used for realistic simulation of Tsunami waves going upstream around shoreline. Tests were made in Tokyo Bay (in 2014) and Osaka Bay (in 2015). The purpose the test in Osaka Bay is to make coastal map for disaster prevention as a countermeasure for predicted Nankai massive earthquake. In addition to Tsunami simulation, the continuous data covering land and marine areas are expected to be used effectively for maintenance and repair of aged port and river facilities, maintenance and investigation of dykes, and ecosystem preservation.

  7. C3d enhanced DNA vaccination induced humoral immune response to glycoprotein C of pseudorabies virus

    International Nuclear Information System (INIS)

    Murine C3d were utilized to enhance immunogenicity of pseudorabies virus (PrV) gC DNA vaccination. Three copies of C3d and four copies of CR2-binding domain M284 were fused, respectively, to truncated gC gene encoding soluble glycoprotein C (sgC) in pcDNA3.1. BALB/c mice were, respectively, immunized with recombinant plasmids, blank vector, and inactivated vaccine. The antibody ELISA titer for sgC-C3d3 DNA was 49-fold more than that for sgC DNA, and the neutralizing antibody obtained 8-fold rise. Protection of mice from death after lethal PrV (316 LD5) challenge was augmented from 25% to 100%. Furthermore, C3d fusion increased Th2-biased immune response by inducing IL-4 production. The IL-4 level for sgC-C3d3 DNA immunization approached that for the inactivated vaccine. Compared to C3d, M28 enhanced sgC DNA immunogenicity to a lesser extent. In conclusion, we demonstrated that murine C3d fusion significantly enhanced gC DNA immunity by directing Th1-biased to a balanced and more effective Th1/Th2 response

  8. Discovery of Small Molecules for Fluorescent Detection of Complement Activation Product C3d.

    Science.gov (United States)

    Gorham, Ronald D; Nuñez, Vicente; Lin, Jung-Hsin; Rooijakkers, Suzan H M; Vullev, Valentine I; Morikis, Dimitrios

    2015-12-24

    Complement activation plays a major role in many acute and chronic inflammatory conditions. C3d, a terminal product of complement activation, remains covalently attached to cells and is an excellent biomarker of complement-mediated inflammation. We employed a virtual high-throughput screening protocol to identify molecules with predicted binding to complement C3d and with intrinsic fluorescence properties to enable detection. Pharmacophore models were developed based on known C3d-ligand interactions and information from computational analysis of structural and molecular dynamics data. Iterative pharmacophore-based virtual screening was performed to identify druglike molecules with physicochemical similarity to the natural C3d ligand CR2. Hits from the pharmacophore screens were docked to C3d and ranked based on predicted binding free energies. Top-ranked molecules were selected for experimental validation of binding affinity to C3d, using microscale thermophoresis, and for their suitability to become molecular imaging agents, using fluorescence spectroscopy. This work serves as a foundation for identifying additional fluorescent molecules with high-affinity for C3d that will subsequently be explored as noninvasive in vivo diagnostics of complement-mediated inflammation, for spatiotemporal monitoring of disease progression, and for targeting therapeutics to sites of inflammation. PMID:26613117

  9. Discovery of Small Molecules for Fluorescent Detection of Complement Activation Product C3d.

    Science.gov (United States)

    Gorham, Ronald D; Nuñez, Vicente; Lin, Jung-Hsin; Rooijakkers, Suzan H M; Vullev, Valentine I; Morikis, Dimitrios

    2015-12-24

    Complement activation plays a major role in many acute and chronic inflammatory conditions. C3d, a terminal product of complement activation, remains covalently attached to cells and is an excellent biomarker of complement-mediated inflammation. We employed a virtual high-throughput screening protocol to identify molecules with predicted binding to complement C3d and with intrinsic fluorescence properties to enable detection. Pharmacophore models were developed based on known C3d-ligand interactions and information from computational analysis of structural and molecular dynamics data. Iterative pharmacophore-based virtual screening was performed to identify druglike molecules with physicochemical similarity to the natural C3d ligand CR2. Hits from the pharmacophore screens were docked to C3d and ranked based on predicted binding free energies. Top-ranked molecules were selected for experimental validation of binding affinity to C3d, using microscale thermophoresis, and for their suitability to become molecular imaging agents, using fluorescence spectroscopy. This work serves as a foundation for identifying additional fluorescent molecules with high-affinity for C3d that will subsequently be explored as noninvasive in vivo diagnostics of complement-mediated inflammation, for spatiotemporal monitoring of disease progression, and for targeting therapeutics to sites of inflammation.

  10. Capillary Deposition of Complement C4d and C3d in Chinese Renal Allograft Biopsies

    Directory of Open Access Journals (Sweden)

    Rong Lv

    2015-01-01

    Full Text Available Background. C3d is a product of both the classic and the alternative complement cascades; however, few studies have addressed the role of C3d in renal biopsies and its relationship with long-term graft survival rate is not very clear. Methods. 94 patients with biopsy-proven acute rejection episodes were included in the study. We investigated the associations between histological findings, clinical examinations, and outcome. Results. The overall prevalence for C4dPTC and C3dPTC was 42.6% and 29.8%. There was a significant association between C3dPTC and C4dPTC (P<0.001. C3dPTC and C4dPTC were related with histological types (P=0.024 and P<0.001, resp.. The long-term survival rate for C4dPTC positive transplants was lower than that of C4dPTC negative transplants, but it was not statistic significant in our study (P=0.150. The survival rate of C3dPTC positive group was much lower than the negative group (P=0.014. Patients with double positives for C4dPTC and C3dPTC exhibited the lowest survival rate significantly different from those of the C3dPTC only and C4dPTC only groups (P=0.01 and P=0.0037. Conclusions. This longitudinal cohort study has demonstrated that C3d deposition in the PTC was closely related to renal dysfunction and pathological changes.

  11. Glomerular C3d as a novel prognostic marker for renal vasculitis.

    Science.gov (United States)

    Villacorta, Javier; Diaz-Crespo, Francisco; Acevedo, Mercedes; Guerrero, Carmen; Campos-Martin, Yolanda; García-Díaz, Eugenio; Mollejo, Manuela; Fernandez-Juarez, Gema

    2016-10-01

    Pauci-immune necrotizing crescentic glomerulonephritis is the histologic substrate of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Several studies in animal models have demonstrated the crucial role of complement activation in the pathogenesis of ANCA-associated vasculitis, but only small series have analyzed the prognostic implications of complement glomerular deposits. This study aimed to assess the clinical and prognostic implications of C3d- and C4d-positive glomerular staining in renal vasculitis. Eighty-five patients with a diagnosis of pauci-immune necrotizing crescentic glomerulonephritis were included in the study. C3d and C4d were analyzed by immunohistochemical staining using a polyclonal antibody. The primary predictors were glomerular C3d- and C4d-positive staining. The primary end point was the cumulative percentage of patients who developed end-stage renal disease. Glomerular staining for C3d and C4d was observed in 42 (49.4%) of 85 biopsies and 38 (44.7%) of 85 biopsies, respectively. C3d-positive staining was associated with the severity of renal impairment and with a lower response rate to treatment (P=.003 and P=.04, respectively). Renal survival at 2 and 5 years was 60.9% and 51.8% in C3d-positive patients compared with 87.7% and 78.9% in C3d-negative patients (P=.04). C4d-positive staining did not show any impact in renal outcome. When adjusted by renal function and other histologic parameters, C3d staining remained as an independent predictor for renal survival (hazard ratio, 2.5; 95% confidence interval, 1.1-5.7; P=.03). Therefore, this study demonstrates that C3d-positive glomerular staining is an independent risk factor for the development of end-stage renal disease in ANCA-associated renal vasculitis.

  12. Mutational analysis of the complement receptor type 2 (CR2/CD21)-C3d interaction reveals a putative charged SCR1 binding site for C3d.

    Science.gov (United States)

    Hannan, Jonathan P; Young, Kendra A; Guthridge, Joel M; Asokan, Rengasamy; Szakonyi, Gerda; Chen, Xiaojiang S; Holers, V Michael

    2005-02-25

    We have characterized the interaction between the first two short consensus repeats (SCR1-2) of complement receptor type 2 (CR2, CD21) and C3d in solution, by utilising the available crystal structures of free and C3d-bound forms of CR2 to create a series of informative mutations targeting specific areas of the CR2-C3d complex. Wild-type and mutant forms of CR2 were expressed on the surface of K562 erythroleukemia cells and their binding ability assessed using C3dg-biotin tetramers complexed to fluorochrome conjugated streptavidin and measured by flow cytometry. Mutations directed at the SCR2-C3d interface (R83A, R83E, G84Y) were found to strongly disrupt C3dg binding, supporting the conclusion that the SCR2 interface reflected in the crystal structure is correct. Previous epitope and peptide mapping studies have also indicated that the PILN11GR13IS sequence of the first inter-cysteine region of SCR1 is essential for the binding of iC3b. Mutations targeting residues within or in close spatial proximity to this area (N11A, N11E, R13A, R13E, Y16A, S32A, S32E), and a number of other positively charged residues located primarily on a contiguous face of SCR1 (R28A, R28E, R36A, R36E, K41A, K41E, K50A, K50E, K57A, K57E, K67A, K67E), have allowed us to reassess those regions on SCR1 that are essential for CR2-C3d binding. The nature of this interaction and the possibility of a direct SCR1-C3d association are discussed extensively. Finally, a D52N mutant was constructed introducing an N-glycosylation sequence at an area central to the CR2 dimer interface. This mutation was designed to disrupt the CR2-C3d interaction, either directly through steric inhibition, or indirectly through disruption of a physiological dimer. However, no difference in C3dg binding relative to wild-type CR2 could be observed for this mutant, suggesting that the dimer may only be found in the crystal form of CR2. PMID:15713467

  13. Mutational analysis of the complement receptor type 2 (CR2/CD21)-C3d interaction reveals a putative charged SCR1 binding site for C3d.

    Science.gov (United States)

    Hannan, Jonathan P; Young, Kendra A; Guthridge, Joel M; Asokan, Rengasamy; Szakonyi, Gerda; Chen, Xiaojiang S; Holers, V Michael

    2005-02-25

    We have characterized the interaction between the first two short consensus repeats (SCR1-2) of complement receptor type 2 (CR2, CD21) and C3d in solution, by utilising the available crystal structures of free and C3d-bound forms of CR2 to create a series of informative mutations targeting specific areas of the CR2-C3d complex. Wild-type and mutant forms of CR2 were expressed on the surface of K562 erythroleukemia cells and their binding ability assessed using C3dg-biotin tetramers complexed to fluorochrome conjugated streptavidin and measured by flow cytometry. Mutations directed at the SCR2-C3d interface (R83A, R83E, G84Y) were found to strongly disrupt C3dg binding, supporting the conclusion that the SCR2 interface reflected in the crystal structure is correct. Previous epitope and peptide mapping studies have also indicated that the PILN11GR13IS sequence of the first inter-cysteine region of SCR1 is essential for the binding of iC3b. Mutations targeting residues within or in close spatial proximity to this area (N11A, N11E, R13A, R13E, Y16A, S32A, S32E), and a number of other positively charged residues located primarily on a contiguous face of SCR1 (R28A, R28E, R36A, R36E, K41A, K41E, K50A, K50E, K57A, K57E, K67A, K67E), have allowed us to reassess those regions on SCR1 that are essential for CR2-C3d binding. The nature of this interaction and the possibility of a direct SCR1-C3d association are discussed extensively. Finally, a D52N mutant was constructed introducing an N-glycosylation sequence at an area central to the CR2 dimer interface. This mutation was designed to disrupt the CR2-C3d interaction, either directly through steric inhibition, or indirectly through disruption of a physiological dimer. However, no difference in C3dg binding relative to wild-type CR2 could be observed for this mutant, suggesting that the dimer may only be found in the crystal form of CR2.

  14. Epstein Barr virus/complement C3d receptor is an interferon alpha receptor.

    OpenAIRE

    Delcayre, A X; Salas, F.; Mathur, S; Kovats, K; Lotz, M.; Lernhardt, W

    1991-01-01

    Interferon alpha contains a sequence motif similar to the complement receptor type two (CR2/CD21) binding site on complement fragment C3d. Antibodies against a peptide with the CR2 binding sequence on C3d react with a peptide carrying the IFN alpha CR2 binding motif (residues 92-99) and with recombinant IFN alpha. The IFN alpha-derived peptide, as well as recombinant IFN alpha, inhibits C3bi/C3d interaction with CR2 on the Burkitt lymphoma Raji. The direct interaction of IFN alpha and CR2 is ...

  15. Novel function of complement C3d as an autologous helper T-cell target.

    Science.gov (United States)

    Knopf, Paul M; Rivera, Daniel S; Hai, Si-Han; McMurry, Julie; Martin, William; De Groot, Anne S

    2008-01-01

    The C3d fragment of complement component C3 has been shown to enhance immune responses to antigens that lack T-cell epitopes such as bacterial polysaccharides. C3d binds to the B-cell complement receptor 2 (CR2 or CD21); this binding serves as a co-activation signal to the B cell when the polysaccharide antigen portion binds simultaneously to the B-cell receptor (surface Ig). Bringing together receptor-associated signal transduction molecules CD19 and Igalpha/beta, respectively, results in a lower threshold of activation. Paradoxically, C3d has also been shown to enhance antibody titers in the CD21 knockout (KO) mouse model as well as increase Th1 and Th2 cytokine secretion, suggesting that that an auxiliary CR2-independent pathway of immune activation may exist. We hypothesized that in addition to its molecular adjuvant property that enhances signal 1 during B-cell activation (co-signal 1), C3d also contains T-cell epitopes that are able to stimulate autoreactive C3d peptide-specific helper T cells which we term 'co-signal 2'. Using the EpiMatrix T-cell epitope-mapping algorithm, we identified 11 putative T-cell epitopes in C3d, a very high epitope density for a 302 amino-acid sequence. Eight of these epitope candidates were synthesized and shown to bind a variety of class II HLA-DR molecules of different haplotypes, and to stimulate C3d peptide-specific T cells to secrete pro-inflammatory cytokines in vitro. Further, we demonstrate a C3d-peptide specific increase in CD4(+) intracellular IFN-gamma(+) T cells in peripheral blood mononuclear cells (PBMCs) exposed to C3d peptides in vitro. We believe that the discovery of these autologous T cells autoreactive for C3d provides evidence supporting the 'co-signal 2' hypothesis and may offer a novel explanation of the CD21 KO paradox. PMID:18180801

  16. FHR3 Blocks C3d-Mediated Coactivation of Human B Cells.

    Science.gov (United States)

    Buhlmann, Denise; Eberhardt, Hannes U; Medyukhina, Anna; Prodinger, Wolfgang M; Figge, Marc Thilo; Zipfel, Peter F; Skerka, Christine

    2016-07-15

    The autoimmune renal disease deficient for complement factor H-related (CFHR) genes and autoantibody-positive form of hemolytic uremic syndrome is characterized by the presence of autoantibodies specific for the central complement regulator, factor H, combined with a homozygous deficiency, mostly in CFHR3 and CFHR1 Because FHR3 and FHR1 bind to C3d and inactivated C3b, which are ligands for complement receptor type 2 (CR2/CD21), the aim of the current study was to examine whether FHR3-C3d or FHR1-C3d complexes modulate B cell activation. Laser-scanning microscopy and automated image-based analysis showed that FHR3, but not FHR1 or factor H, blocked B cell activation by the BCR coreceptor complex (CD19/CD21/CD81). FHR3 bound to C3d, thereby inhibiting the interaction between C3d and CD21 and preventing colocalization of the coreceptor complex with the BCR. FHR3 neutralized the adjuvant effect of C3d on B cells, as shown by inhibited intracellular CD19 and Akt phosphorylation in Raji cells, as well as Ca(2+) release in peripheral B cells. In cases of CFHR3/CFHR1 deficiency, the FHR3 binding sites on C3d are occupied by factor H, which lacks B cell-inhibitory functions. These data provide evidence that FHR3, which is absent in patients with the autoimmune form of hemolytic uremic syndrome, is involved in B cell regulation. PMID:27279373

  17. Structure of complement receptor 2 in complex with its C3d ligand.

    Science.gov (United States)

    Szakonyi, G; Guthridge, J M; Li, D; Young, K; Holers, V M; Chen, X S

    2001-06-01

    Complement receptor 2 (CR2/CD21) is an important receptor that amplifies B lymphocyte activation by bridging the innate and adaptive immune systems. CR2 ligands include complement C3d and Epstein-Barr virus glycoprotein 350/220. We describe the x-ray structure of this CR2 domain in complex with C3d at 2.0 angstroms. The structure reveals extensive main chain interactions between C3d and only one short consensus repeat (SCR) of CR2 and substantial SCR side-side packing. These results provide a detailed understanding of receptor-ligand interactions in this protein family and reveal potential target sites for molecular drug design. PMID:11387479

  18. Effect of Ductile Agents on the Dynamic Behavior of SiC3D Network Composites

    Science.gov (United States)

    Zhu, Jingbo; Wang, Yangwei; Wang, Fuchi; Fan, Qunbo

    2016-10-01

    Co-continuous SiC ceramic composites using pure aluminum, epoxy, and polyurethane (PU) as ductile agents were developed. The dynamic mechanical behavior and failure mechanisms were investigated experimentally using the split Hopkinson pressure bar (SHPB) method and computationally by finite element (FE) simulations. The results show that the SiC3D/Al composite has the best overall performance in comparison with SiC3D/epoxy and SiC3D/PU composites. FE simulations are generally consistent with experimental data. These simulations provide valuable help in predicting mechanical strength and in interpreting the experimental results and failure mechanisms. They may be combined with micrographs for fracture characterizations of the composites. We found that interactions between the SiC phase and ductile agents under dynamic compression in the SHPB method are complex, and that interfacial condition is an important parameter that determines the mechanical response of SiC3D composites with a characteristic interlocking structure during dynamic compression. However, the effect of the mechanical properties of ductile agents on dynamic behavior of the composites is a second consideration in the production of the composites.

  19. 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...

  20. Isolation of lymphocyte membrane complement receptor type two (the C3d receptor) and preparation of receptor-specific antibody.

    OpenAIRE

    LAMBRIS, J. D.; Dobson, N J; Ross, G D

    1981-01-01

    A glycoprotein binding complement component C3d was isolated from media used for culture of Raji human lymphoblastoid cells. Analysis by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and gas/liquid chromatography indicated that the C3d-binding glycoprotein consisted of a single polypeptide chain with extensive intrachain disulfide bonds, a molecular weight of 72,000, and several different bound carbohydrates. Several lines of evidence indicated that this medium-derived C3d-binding...

  1. Delineation of the complement receptor type 2-C3d complex by site-directed mutagenesis and molecular docking.

    Science.gov (United States)

    Shaw, Craig D; Storek, Michael J; Young, Kendra A; Kovacs, James M; Thurman, Joshua M; Holers, V Michael; Hannan, Jonathan P

    2010-12-10

    The interactions between the complement receptor type 2 (CR2) and the C3 complement fragments C3d, C3dg, and iC3b are essential for the initiation of a normal immune response. A crystal-derived structure of the two N-terminal short consensus repeat (SCR1-2) domains of CR2 in complex with C3d has previously been elucidated. However, a number of biochemical and biophysical studies targeting both CR2 and C3d appear to be in conflict with these structural data. Previous mutagenesis and heteronuclear NMR spectroscopy studies directed toward the C3d-binding site on CR2 have indicated that the CR2-C3d cocrystal structure may represent an encounter/intermediate or nonphysiological complex. With regard to the CR2-binding site on C3d, mutagenesis studies by Isenman and coworkers [Isenman, D. E., Leung, E., Mackay, J. D., Bagby, S. & van den Elsen, J. M. H. (2010). Mutational analyses reveal that the staphylococcal immune evasion molecule Sbi and complement receptor 2 (CR2) share overlapping contact residues on C3d: Implications for the controversy regarding the CR2/C3d cocrystal structure. J. Immunol. 184, 1946-1955] have implicated an electronegative "concave" surface on C3d in the binding process. This surface is discrete from the CR2-C3d interface identified in the crystal structure. We generated a total of 18 mutations targeting the two (X-ray crystallographic- and mutagenesis-based) proposed CR2 SCR1-2 binding sites on C3d. Using ELISA analyses, we were able to assess binding of mutant forms of C3d to CR2. Mutations directed toward the concave surface of C3d result in substantially compromised CR2 binding. By contrast, targeting the CR2-C3d interface identified in the cocrystal structure and the surrounding area results in significantly lower levels of disruption in binding. Molecular modeling approaches used to investigate disparities between the biochemical data and the X-ray structure of the CR2-C3d cocrystal result in highest-scoring solutions in which CR2 SCR1-2 is

  2. Delineation of the complement receptor type 2-C3d complex by site-directed mutagenesis and molecular docking.

    Science.gov (United States)

    Shaw, Craig D; Storek, Michael J; Young, Kendra A; Kovacs, James M; Thurman, Joshua M; Holers, V Michael; Hannan, Jonathan P

    2010-12-10

    The interactions between the complement receptor type 2 (CR2) and the C3 complement fragments C3d, C3dg, and iC3b are essential for the initiation of a normal immune response. A crystal-derived structure of the two N-terminal short consensus repeat (SCR1-2) domains of CR2 in complex with C3d has previously been elucidated. However, a number of biochemical and biophysical studies targeting both CR2 and C3d appear to be in conflict with these structural data. Previous mutagenesis and heteronuclear NMR spectroscopy studies directed toward the C3d-binding site on CR2 have indicated that the CR2-C3d cocrystal structure may represent an encounter/intermediate or nonphysiological complex. With regard to the CR2-binding site on C3d, mutagenesis studies by Isenman and coworkers [Isenman, D. E., Leung, E., Mackay, J. D., Bagby, S. & van den Elsen, J. M. H. (2010). Mutational analyses reveal that the staphylococcal immune evasion molecule Sbi and complement receptor 2 (CR2) share overlapping contact residues on C3d: Implications for the controversy regarding the CR2/C3d cocrystal structure. J. Immunol. 184, 1946-1955] have implicated an electronegative "concave" surface on C3d in the binding process. This surface is discrete from the CR2-C3d interface identified in the crystal structure. We generated a total of 18 mutations targeting the two (X-ray crystallographic- and mutagenesis-based) proposed CR2 SCR1-2 binding sites on C3d. Using ELISA analyses, we were able to assess binding of mutant forms of C3d to CR2. Mutations directed toward the concave surface of C3d result in substantially compromised CR2 binding. By contrast, targeting the CR2-C3d interface identified in the cocrystal structure and the surrounding area results in significantly lower levels of disruption in binding. Molecular modeling approaches used to investigate disparities between the biochemical data and the X-ray structure of the CR2-C3d cocrystal result in highest-scoring solutions in which CR2 SCR1-2 is

  3. Polyspecific pyrrolysyl-tRNA synthetases from directed evolution

    Science.gov (United States)

    Guo, Li-Tao; Wang, Yane-Shih; Nakamura, Akiyoshi; Eiler, Daniel; Kavran, Jennifer M.; Wong, Margaret; Kiessling, Laura L.; Steitz, Thomas A.; O’Donoghue, Patrick; Söll, Dieter

    2014-01-01

    Pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNAPyl have emerged as ideal translation components for genetic code innovation. Variants of the enzyme facilitate the incorporation >100 noncanonical amino acids (ncAAs) into proteins. PylRS variants were previously selected to acylate Nε-acetyl-Lys (AcK) onto tRNAPyl. Here, we examine an Nε-acetyl-lysyl-tRNA synthetase (AcKRS), which is polyspecific (i.e., active with a broad range of ncAAs) and 30-fold more efficient with Phe derivatives than it is with AcK. Structural and biochemical data reveal the molecular basis of polyspecificity in AcKRS and in a PylRS variant [iodo-phenylalanyl-tRNA synthetase (IFRS)] that displays both enhanced activity and substrate promiscuity over a chemical library of 313 ncAAs. IFRS, a product of directed evolution, has distinct binding modes for different ncAAs. These data indicate that in vivo selections do not produce optimally specific tRNA synthetases and suggest that translation fidelity will become an increasingly dominant factor in expanding the genetic code far beyond 20 amino acids. PMID:25385624

  4. Polyspecific pyrrolysyl-tRNA synthetases from directed evolution.

    Science.gov (United States)

    Guo, Li-Tao; Wang, Yane-Shih; Nakamura, Akiyoshi; Eiler, Daniel; Kavran, Jennifer M; Wong, Margaret; Kiessling, Laura L; Steitz, Thomas A; O'Donoghue, Patrick; Söll, Dieter

    2014-11-25

    Pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNA(Pyl) have emerged as ideal translation components for genetic code innovation. Variants of the enzyme facilitate the incorporation >100 noncanonical amino acids (ncAAs) into proteins. PylRS variants were previously selected to acylate N(ε)-acetyl-Lys (AcK) onto tRNA(Pyl). Here, we examine an N(ε)-acetyl-lysyl-tRNA synthetase (AcKRS), which is polyspecific (i.e., active with a broad range of ncAAs) and 30-fold more efficient with Phe derivatives than it is with AcK. Structural and biochemical data reveal the molecular basis of polyspecificity in AcKRS and in a PylRS variant [iodo-phenylalanyl-tRNA synthetase (IFRS)] that displays both enhanced activity and substrate promiscuity over a chemical library of 313 ncAAs. IFRS, a product of directed evolution, has distinct binding modes for different ncAAs. These data indicate that in vivo selections do not produce optimally specific tRNA synthetases and suggest that translation fidelity will become an increasingly dominant factor in expanding the genetic code far beyond 20 amino acids.

  5. The use of C3d as a means of monitoring clinical activity in systemic lupus erythematosus and rheumatoid arthritis.

    OpenAIRE

    Morrow, W J; Williams, D. J.; Ferec, C.; Casburn-Budd, R; Isenberg, D. A.; Paice, E; Snaith, M L; Youinou, P; Le Goff, P

    1983-01-01

    Plasma samples from 44 patients with systemic lupus erythematosus (SLE) and 43 with rheumatoid arthritis (RA) were assayed for C3d, a breakdown product of the third component of complement (C3), which was also measured in parallel. Levels of C3d varied in direct proportion with disease activity in RA, whereas C3 showed little change. Although C3d values also increased with worsening clinical condition in SLE, this trend was not considered to be sufficiently clear to be useful and did not prov...

  6. Complement C3d conjugation to anthrax protective antigen promotes a rapid, sustained, and protective antibody response.

    Directory of Open Access Journals (Sweden)

    Ravi V Kolla

    Full Text Available B. anthracis is the causative agent of anthrax. Pathogenesis is primarily mediated through the exotoxins lethal factor and edema factor, which bind protective antigen (PA to gain entry into the host cell. The current anthrax vaccine (AVA, Biothrax consists of aluminum-adsorbed cell-free filtrates of unencapsulated B. anthracis, wherein PA is thought to be the principle target of neutralization. In this study, we evaluated the efficacy of the natural adjuvant, C3d, versus alum in eliciting an anti-PA humoral response and found that C3d conjugation to PA and emulsion in incomplete Freund's adjuvant (IFA imparted superior protection from anthrax challenge relative to PA in IFA or PA adsorbed to alum. Relative to alum-PA, immunization of mice with C3d-PA/IFA augmented both the onset and sustained production of PA-specific antibodies, including neutralizing antibodies to the receptor-binding portion (domain 4 of PA. C3d-PA/IFA was efficacious when administered either i.p. or s.c., and in adolescent mice lacking a fully mature B cell compartment. Induction of PA-specific antibodies by C3d-PA/IFA correlated with increased efficiency of germinal center formation and plasma cell generation. Importantly, C3d-PA immunization effectively protected mice from intranasal challenge with B. anthracis spores, and was approximately 10-fold more effective than alum-PA immunization or PA/IFA based on dose challenge. These data suggest that incorporation of C3d as an adjuvant may overcome shortcomings of the currently licensed aluminum-based vaccine, and may confer protection in the early days following acute anthrax exposure.

  7. The two sides of complement C3d: evolution of electrostatics in a link between innate and adaptive immunity.

    Directory of Open Access Journals (Sweden)

    Chris A Kieslich

    Full Text Available The interaction between complement fragment C3d and complement receptor 2 (CR2 is a key aspect of complement immune system activation, and is a component in a link between innate and adaptive immunities. The complement immune system is an ancient mechanism for defense, and can be found in species that have been on Earth for the last 600 million years. However, the link between the complement system and adaptive immunity, which is formed through the association of the B-cell co-receptor complex, including the C3d-CR2 interaction, is a much more recent adaptation. Human C3d and CR2 have net charges of -1 and +7 respectively, and are believed to have evolved favoring the role of electrostatics in their functions. To investigate the role of electrostatics in the function and evolution of human C3d and CR2, we have applied electrostatic similarity methods to identify regions of evolutionarily conserved electrostatic potential based on 24 homologues of complement C3d and 4 homologues of CR2. We also examine the effects of structural perturbation, as introduced through molecular dynamics and mutations, on spatial distributions of electrostatic potential to identify perturbation resistant regions, generated by so-called electrostatic "hot-spots". Distributions of electrostatic similarity based on families of perturbed structures illustrate the presence of electrostatic "hot-spots" at the two functional sites of C3d, while the surface of CR2 lacks electrostatic "hot-spots" despite its excessively positive nature. We propose that the electrostatic "hot-spots" of C3d have evolved to optimize its dual-functionality (covalently attaching to pathogen surfaces and interaction with CR2, which are both necessary for the formation B-cell co-receptor complexes. Comparison of the perturbation resistance of the electrostatic character of the homologues of C3d suggests that there was an emergence of a new role of electrostatics, and a transition in the function of C3

  8. Enhancement of Antibodies to the Human Immunodeficiency Virus Type 1 Envelope by Using the Molecular Adjuvant C3d

    OpenAIRE

    Green, Thomas D.; David C Montefiori; Ross, Ted M.

    2003-01-01

    DNA vaccines expressing the envelope (Env) protein of the human immunodeficiency virus have been relatively ineffective at generating high-titer, long-lasting, neutralizing antibodies in a variety of animal models. In this study, the murine and human homologues of the complement component, C3d, were used in a DNA vaccine to enhance the titers of antibody to Env. Initially, plasmids expressing a secreted form of Env (sgp120) fused to one, two, or three copies of the murine homologue of C3d (mC...

  9. Impact of the common genetic associations of age-related macular degeneration upon systemic complement component C3d levels.

    Directory of Open Access Journals (Sweden)

    Tina Ristau

    Full Text Available Age-related macular degeneration (AMD is a common condition that leads to severe vision loss and dysregulation of the complement system is thought to be associated with the disease. To investigate associations of polymorphisms in AMD susceptibility genes with systemic complement activation, 2655 individuals were genotyped for 32 single nucleotide polymorphisms (SNPs in or near 23 AMD associated risk genes. Component 3 (C3 and its catabolic fragment C3d were measured in serum and AMD staging was performed using multimodal imaging. The C3d/C3 ratio was calculated and associations with environmental factors, SNPs and various haplotypes of complement factor H (CFH genes and complement factor B (CFB genes were analyzed. Linear models were built to measure the influence of genetic variants on the C3d/C3 ratio. The study cohort included 1387 patients with AMD and 1268 controls. Higher C3d/C3 ratios were found for current smoker (p = 0.002, higher age (p = 1.56 × 10(-7, AMD phenotype (p = 1.15 × 10(-11 and the two SNPs in the C3 gene rs6795735 (p = 0.04 and rs2230199 (p = 0.04. Lower C3d/C3 ratios were found for diabetes (p = 2.87 × 10(-6, higher body mass index (p = 1.00 × 10(-13, the SNPs rs1410996 (p = 0.0001, rs800292 (p = 0.003, rs12144939 (p = 4.60 × 10(-6 in CFH, rs4151667 (p = 1.01 × 10(-5 in CFB and individual haplotypes in CFH and CFB. The linear model revealed a corrected R-square of 0.063 including age, smoking status, gender, and genetic polymorphisms explaining 6.3% of the C3d/C3 ratio. After adding the AMD status the corrected R-square was 0.067. In conclusion, none of the evaluated genetic polymorphisms showed an association with increased systemic complement activation apart from two SNPs in the C3 gene. Major genetic and non-genetic factors for AMD were not associated with systemic complement activation.

  10. C3d fragment of complement interacts with laminin and binds to basement membranes of glomerulus and trophoblast

    OpenAIRE

    1986-01-01

    Two mouse monoclonal antibodies generated against human placental homogenate were found to react specifically with human complement component C3. In immunofluorescence of human tissues, these antibodies gave a bright linear staining outlining the glomerular basement membrane of the adult kidney and the trophoblast basement membrane of placenta. An identical staining pattern was observed with a rabbit C3d antiserum which also prevented binding of the monoclonal antibodies to tissue sections. O...

  11. Pneumococcal polysaccharides complexed with C3d bind to human B lymphocytes via complement receptor type 2.

    OpenAIRE

    Griffioen, A W; Rijkers, G T; Janssens-Korpela, P; Zegers, B J

    1991-01-01

    The immunoregulatory function of the complement system has been the focus of many investigations. In particular, fragments of complement factor C3 have been shown to play a role in B-lymphocyte activation and proliferation, lymphokine production, and the generation of in vitro antibody production. Purified pneumococcal polysaccharides (PS) can induce direct activation of C3 via the alternative pathway. Using sera of C1q-deficient patients and healthy subjects, we demonstrated that C3d, a spli...

  12. Towards 3C-3D digital holographic fluid velocity vector field measurement—tomographic digital holographic PIV (Tomo-HPIV)

    International Nuclear Information System (INIS)

    Most unsteady and/or turbulent flows of geophysical and engineering interest have a highly three-dimensional (3D) complex topology and their experimental investigation is in pressing need of quantitative velocity measurement methods that are robust and can provide instantaneous 3C-3D velocity field data over a significant volumetric domain of the flow. This paper introduces and demonstrates a new method that uses multiple digital CCD array cameras to record in-line digital holograms of the same volume of seed particles from multiple orientations. This technique uses the same basic equipment as Tomo-PIV minus the camera lenses, it overcomes the depth-of-field problem of digital in-line holography and does not require the complex optical calibration of Tomo-PIV. The digital sensors can be oriented in an optimal manner to overcome the depth-of-field limitation of in-line holograms recorded using digital CCD or CMOS array cameras, resulting in a 3D reconstruction of the seed particles within the volume of interest, which can subsequently be analysed using 3D cross-correlation PIV analysis to yield a 3C-3D velocity field. A demonstration experiment of Tomo-HPIV using uniform translation with nominally 11 µm diameter seed particles shows that the 3D displacement derived from 3D cross-correlation Tomo-HPIV analysis can be measured within 5% of the imposed uniform translation, where the imposed uniform translation has an estimated standard uncertainty of 4.3%. So this paper proposes a multi-camera digital holographic imaging 3C-3D PIV method, which is identified as tomographic digital holographic PIV or Tomo-HPIV

  13. Towards 3C-3D digital holographic fluid velocity vector field measurement—tomographic digital holographic PIV (Tomo-HPIV)

    Science.gov (United States)

    Soria, J.; Atkinson, C.

    2008-07-01

    Most unsteady and/or turbulent flows of geophysical and engineering interest have a highly three-dimensional (3D) complex topology and their experimental investigation is in pressing need of quantitative velocity measurement methods that are robust and can provide instantaneous 3C-3D velocity field data over a significant volumetric domain of the flow. This paper introduces and demonstrates a new method that uses multiple digital CCD array cameras to record in-line digital holograms of the same volume of seed particles from multiple orientations. This technique uses the same basic equipment as Tomo-PIV minus the camera lenses, it overcomes the depth-of-field problem of digital in-line holography and does not require the complex optical calibration of Tomo-PIV. The digital sensors can be oriented in an optimal manner to overcome the depth-of-field limitation of in-line holograms recorded using digital CCD or CMOS array cameras, resulting in a 3D reconstruction of the seed particles within the volume of interest, which can subsequently be analysed using 3D cross-correlation PIV analysis to yield a 3C-3D velocity field. A demonstration experiment of Tomo-HPIV using uniform translation with nominally 11 µm diameter seed particles shows that the 3D displacement derived from 3D cross-correlation Tomo-HPIV analysis can be measured within 5% of the imposed uniform translation, where the imposed uniform translation has an estimated standard uncertainty of 4.3%. So this paper proposes a multi-camera digital holographic imaging 3C-3D PIV method, which is identified as tomographic digital holographic PIV or Tomo-HPIV.

  14. Interactions of complement receptor type 2 with C3d and factor H with C3u

    OpenAIRE

    Li, K

    2010-01-01

    Complement receptor type 2 (CR2, CD21) is a cell surface protein that links the innate and adaptive immune response through its binding to C3d, a cleavage fragment of the major complement component C3. Factor H (FH) is a major plasma protein that is the major regulator of the activity of C3b in the alternative pathway. FH binds to C3u, which is formed from C3 by hydrolysis, and C3u shows functional similarities to C3b. In this thesis, X-ray scattering, analytical ultracentrifug...

  15. The Two Sides of Complement C3d: Evolution of Electrostatics in a Link between Innate and Adaptive Immunity

    OpenAIRE

    Kieslich, Chris A.; Dimitrios Morikis

    2012-01-01

    The interaction between complement fragment C3d and complement receptor 2 (CR2) is a key aspect of complement immune system activation, and is a component in a link between innate and adaptive immunities. The complement immune system is an ancient mechanism for defense, and can be found in species that have been on Earth for the last 600 million years. However, the link between the complement system and adaptive immunity, which is formed through the association of the B-cell co-receptor compl...

  16. gp140, the C3d receptor of human B lymphocytes, is also the Epstein-Barr virus receptor.

    OpenAIRE

    Frade, R; Barel, M; Ehlin-Henriksson, B.; Klein, G

    1985-01-01

    The relationship between gp140, the membrane C3d receptor (CR2) of human B lymphocytes, and the Epstein-Barr virus receptor (EBVR) was analyzed by using the polyclonal anti-gp140, previously prepared by immunizing rabbits with highly purified gp140 (isolated by some of us) from CR2/EBVR-positive Raji cells. Polyclonal anti-gp72, a C3-binding membrane component, not related to the EBVR but also expressed on the Raji cell surface, was used as a control. Binding of rabbit IgG and EBV on cells wa...

  17. Epstein-Barr virus (EBV) infection of murine L cells expressing recombinant human EBV/C3d receptor.

    OpenAIRE

    Ahearn, J M; Hayward, S D; Hickey, J C; Fearon, D T

    1988-01-01

    The normal host range of Epstein-Barr virus (EBV) is limited to primate B lymphocytes and certain epithelial cells that express the C3d/EBV receptor [complement receptor 2 (CR2, CD21)]. In the present study, expansion of the tissue tropism of EBV has been accomplished by stably transfecting the murine fibroblast L cell line with pMT.CR2. neo.1, a eukaryotic expression vector promoting the transcription of a complementary DNA insert encoding human CR2. High CR2-expressing transfected L cells w...

  18. Construction, expression and immunoassay detection of recombinant plasmid encoding fusion protein of Roman chicken complement C3d and Newcastle disease virus F gene.

    Science.gov (United States)

    Liu, D; Niu, Z-X

    2008-12-01

    The terminal degradation product (C3d) of mammalian complement component C3 plays an important role in modulation of the adaptive immune response through the interaction with complement receptor type 2 (CR2) on B cells. In this study, the gene fragment coding for the complement protein C3d (chC3d) from Roman chicken was cloned and expressed as a fusion protein for its application in the vaccine study of chicken, and for in vitro experiments. The chC3d fragment strengthened B-cell responses when complexed with antigen. Three potential vaccine construct units were engineered to contain two, four and six copies of chC3d coding gene linked to the F gene of Newcastle disease virus (NDV), an economically important pathogen of chicken that is classified as a list A contagious disease of poultry by the Office International des Epizooties. The cloned chC3d protein and different repeats of C3d proteins in addition to the F gene of NDV were generated separately in Escherichia coli and chicken embryo fibroblast cells with the help of expression vectors. All recombinant proteins were analysed by SDS-PAGE and Western blotting. Analysis of the immunogenicity of different repeats of C3d revealed that chC3d had an enhancing effect on the immunogenicity of antigens, and that six or more repeats of C3d may be necessary for efficient enhancement of antigen-specific immune responses. To date, published research into the adjuvant activities of C3d has been limited to experiments in mice, rabbits and cattle. The adjuvant properties of C3d have not been assessed in poultry using homologous C3d in association with antigens relevant to the target species. The Roman chicken C3d fusion proteins described in this study is the first report and will provide a basis for immunization trials in chicken, studies of receptor binding and cell activation of chicken lymphocytes, and investigations of new types of vaccines, including recombinant vaccines and DNA vaccines for future use against other

  19. Identification of a 145,000 Mr membrane protein as the C3d receptor (CR2) of human B lymphocytes.

    OpenAIRE

    Weis, J J; Tedder, T F; D.T. Fearon

    1984-01-01

    The C3d receptor (CR2) of human B lymphocytes mediates the binding to these cells of immune complexes that have activated the complement system and bear the fragments of C3, iC3b, C3d,g, and C3d. A 145,000 Mr membrane protein previously described as being recognized by the monoclonal antibody HB-5 and shown to be expressed only by B lymphocytes and B lymphoblastoid cell lines, such as Raji, was assessed for its possible identity as CR2. Treatment of Raji cells with HB-5 and goat F(ab')2 anti-...

  20. Intravenous Immunoglobulin with Enhanced Polyspecificity Improves Survival in Experimental Sepsis and Aseptic Systemic Inflammatory Response Syndromes

    Science.gov (United States)

    Djoumerska-Alexieva, Iglika; Roumenina, Lubka; Pashov, Anastas; Dimitrov, Jordan; Hadzhieva, Maya; Lindig, Sandro; Voynova, Elisaveta; Dimitrova, Petya; Ivanovska, Nina; Bockmeyer, Clemens; Stefanova, Zvetanka; Fitting, Catherine; Bläss, Markus; Claus, Ralf; von Gunten, Stephan; Kaveri, Srini; Cavaillon, Jean-Marc; Bauer, Michael; Vassilev, Tchavdar

    2015-01-01

    Sepsis is a major cause for death worldwide. Numerous interventional trials with agents neutralizing single proinflammatory mediators have failed to improve survival in sepsis and aseptic systemic inflammatory response syndromes. This failure could be explained by the widespread gene expression dysregulation known as “genomic storm” in these patients. A multifunctional polyspecific therapeutic agent might be needed to thwart the effects of this storm. Licensed pooled intravenous immunoglobulin preparations seemed to be a promising candidate, but they have also failed in their present form to prevent sepsis-related death. We report here the protective effect of a single dose of intravenous immunoglobulin preparations with additionally enhanced polyspecificity in three models of sepsis and aseptic systemic inflammation. The modification of the pooled immunoglobulin G molecules by exposure to ferrous ions resulted in their newly acquired ability to bind some proinflammatory molecules, complement components and endogenous “danger” signals. The improved survival in endotoxemia was associated with serum levels of proinflammatory cytokines, diminished complement consumption and normalization of the coagulation time. We suggest that intravenous immunoglobulin preparations with additionally enhanced polyspecificity have a clinical potential in sepsis and related systemic inflammatory syndromes. PMID:26701312

  1. Clinical Accuracy of Three-Dimensional Fluoroscopy (IsoC-3D-Assisted Upper Thoracic Pedicle Screw Insertion

    Directory of Open Access Journals (Sweden)

    Sugimoto,Yoshihisa

    2010-06-01

    Full Text Available Correct screw placement is especially difficult in the upper thoracic vertebrae. At the cervicothoracic junction (C7-T2, problems can arise because of the narrowness of the pedicle and the difficulty of using a lateral image intensifier there. Other upper thoracic vertebrae (T3-6 pose a problem for screw insertion also because of the narrower pedicle. We inserted 154 pedicle screws into 78 vertebrae (C7 to T6 in 38 patients. Screws were placed using intraoperative data acquisition by an isocentric C-arm fluoroscope (Siremobile Iso-C3D and computer navigation. Out of 90 pedicle screws inserted into 45 vertebrae between C7 and T2, 87 of the 90 (96.7% screws were classified as grade 1 (no perforation. Of 64 pedicle screws inserted into 33 vertebrae between T3 and T6, 61 of 64 (95.3% screws were classified as grade 1. In this study, we reduced pedicle screw misplacement at the level of the C7 and upper thoracic (T1-6 vertebrae using the three-dimensional fluoroscopy navigation system.

  2. gp140, the C3d receptor of human B lymphocytes, is also the Epstein-Barr virus receptor.

    Science.gov (United States)

    Frade, R; Barel, M; Ehlin-Henriksson, B; Klein, G

    1985-03-01

    The relationship between gp140, the membrane C3d receptor (CR2) of human B lymphocytes, and the Epstein-Barr virus receptor (EBVR) was analyzed by using the polyclonal anti-gp140, previously prepared by immunizing rabbits with highly purified gp140 (isolated by some of us) from CR2/EBVR-positive Raji cells. Polyclonal anti-gp72, a C3-binding membrane component, not related to the EBVR but also expressed on the Raji cell surface, was used as a control. Binding of rabbit IgG and EBV on cells was assessed by using immunofluorescence techniques with analysis by flow cytofluorometry. A semiquantitative bioassay was also used to measure the EBV binding. Polyclonal monospecific anti-gp140 IgG inhibits directly the binding of EBV to Raji cells at the same concentration that inhibits the binding of EC3d on cells, whereas a 35 times higher concentration of anti-gp72 IgG or preimmune serum IgG does not. Anti-gp140 IgG treatment also inhibits the induction of EBV-determined nuclear antigen in normal tonsil B lymphocytes or in EBV-negative Ramos cells, whereas high concentrations of anti-gp72 IgG or preimmune serum IgG have no effect. These data strongly suggest that gp140, the CR2 of human B lymphocytes, is also the EBVR. PMID:2983347

  3. Solution structure of the complex between CR2 SCR 1-2 and C3d of human complement: an X-ray scattering and sedimentation modelling study.

    Science.gov (United States)

    Gilbert, Hannah E; Eaton, Julian T; Hannan, Jonathan P; Holers, V Michael; Perkins, Stephen J

    2005-02-25

    Complement receptor type 2 (CR2, CD21) forms a tight complex with C3d, a fragment of C3, the major complement component. Previous crystal structures of the C3d-CR2 SCR 1-2 complex and free CR2 SCR 1-2 showed that the two SCR domains of CR2 form contact with each other in a closed V-shaped structure. SCR 1 and SCR 2 are connected by an unusually long eight-residue linker peptide. Medium-resolution solution structures for CR2 SCR 1-2, C3d, and their complex were determined by X-ray scattering and analytical ultracentrifugation. CR2 SCR 1-2 is monomeric. For CR2 SCR 1-2, its radius of gyration R(G) of 2.12(+/-0.05) nm, its maximum length of 10nm and its sedimentation coefficient s20,w(o) of 1.40(+/-0.03) S do not agree with those calculated from the crystal structures, and instead suggest an open structure. Computer modelling of the CR2 SCR1-2 solution structure was based on the structural randomisation of the eight-residue linker peptide joining SCR 1 and SCR 2 to give 9950 trial models. Comparisons with the X-ray scattering curve indicated that the most favoured arrangements for the two SCR domains corresponded to an open V-shaped structure with no contacts between the SCR domains. For C3d, X-ray scattering and sedimentation velocity experiments showed that it exists as a monomer-dimer equilibrium with a dissociation constant of 40 microM. The X-ray scattering curve for monomeric C3d gave an R(G) value of 1.95 nm, and this together with its s20,w(o) value of 3.17 S gave good agreement with the monomeric C3d crystal structure. Modelling of the C3d dimer gave good agreements with its scattering and ultracentrifugation parameters. For the complex, scattering and ultracentrifugation experiments showed that there was no dimerisation, indicating that the C3d dimerisation site was located close to the CR2 SCR 1-2 binding site. The R(G) value of 2.44(+/-0.1) nm, its length of 9 nm and its s20,w(o) value of 3.45(+/-0.01) S showed that its structure was not much more

  4. C3d-defined complement receptor-binding peptide p28 conjugated to circumsporozoite protein provides protection against Plasmodium berghei.

    Science.gov (United States)

    Bergmann-Leitner, Elke S; Duncan, Elizabeth H; Leitner, Wolfgang W; Neutzner, Albert; Savranskaya, Tatyana; Angov, Evelina; Tsokos, George C

    2007-11-01

    Immune response against circumsporozoite protein (CSP) of Plasmodium berghei, a major surface protein on the sporozoite, confers protection in various murine malaria models. Engineered DNA vaccine encoding CSP and 3 copies of C3d caused an unexpected loss in protection attributed to the binding of C3d to the C-terminal region of CSP. Because the C3d region known as p28 represents the complement receptor (CR) 2-binding motif, we developed a CSP-3 copies of p28 DNA construct (CSP-3p28). CSP-3p28-immunized mice were better protected against P. berghei sporozoites than CSP-immunized mice 6 weeks after the 2nd boost, produced sufficient IgG1 anti-CSP and CSP C-terminus antibody and failed to produce IgG2a. CSP-3C3d-immunized mice were not protected, failed to produce IgG1 and produced high amounts of IgG2a. We conclude that use of the CR2-binding motif of C3d as molecular adjuvant to CSP results in anti-malaria protective immune response probably by targeting the chimeric protein to CR2. PMID:17931754

  5. C3d-defined complement receptor-binding peptide p28 conjugated to circumsporozoite protein provides protection against Plasmodium berghei.

    Science.gov (United States)

    Bergmann-Leitner, Elke S; Duncan, Elizabeth H; Leitner, Wolfgang W; Neutzner, Albert; Savranskaya, Tatyana; Angov, Evelina; Tsokos, George C

    2007-11-01

    Immune response against circumsporozoite protein (CSP) of Plasmodium berghei, a major surface protein on the sporozoite, confers protection in various murine malaria models. Engineered DNA vaccine encoding CSP and 3 copies of C3d caused an unexpected loss in protection attributed to the binding of C3d to the C-terminal region of CSP. Because the C3d region known as p28 represents the complement receptor (CR) 2-binding motif, we developed a CSP-3 copies of p28 DNA construct (CSP-3p28). CSP-3p28-immunized mice were better protected against P. berghei sporozoites than CSP-immunized mice 6 weeks after the 2nd boost, produced sufficient IgG1 anti-CSP and CSP C-terminus antibody and failed to produce IgG2a. CSP-3C3d-immunized mice were not protected, failed to produce IgG1 and produced high amounts of IgG2a. We conclude that use of the CR2-binding motif of C3d as molecular adjuvant to CSP results in anti-malaria protective immune response probably by targeting the chimeric protein to CR2.

  6. Inhibition of B cell growth factor (BCGF) by monoclonal antibodies directed against the C3d receptor (CR2).

    Science.gov (United States)

    Perri, R T; Wilson, B S; Kay, N E

    1986-04-01

    Normal human B cell proliferation is controlled by various immunoregulatory signals including the T cell-derived lymphokine B cell growth factor (BCGF). Human BCGF provides the final proliferative signal to normal, activated B cells. We herein show that anti-CR2 monoclonal antibodies inhibit human B cell responsiveness to purified BCGF. Addition of anti-CR2 antibody, AB5, was capable of completely inhibiting BCGF-mediated enhancement of either anti-mu or staphylococcal protein A-activated human B cells (191 +/- 21 cpm vs. 3942 +/- 622 cpm, mean +/- SEM). Inhibition of B cell response to BCGF by AB5 occurred in a dose-dependent manner. Monoclonal antibody anti-B2, which recognizes the same 140-kDa glycoprotein as AB5, in comparable concentrations also inhibited B cell responsiveness to BCGF. Monoclonal antibodies of the same subclass (IgG1) showed no inhibitory effect on BCGF enhancement of B cell proliferation. The F(ab')2 fragment of AB5 generated by pepsin digestion was similarly inhibitory as was the intact Ig. AB5-mediated inhibition was independent of the target B cell state of activation. Both resting and activated B cells (anti-mu or staphylococcal protein A activated) incubated with similar concentrations of AB5 were unresponsive to BCGF. The ability of anti-CR2 antibodies to block BCGF-dependent B cell proliferation suggests that occupancy of C3d membrane receptors may result in modulation of B cell proliferation in physiologic or clinical disease states. PMID:2938967

  7. Detection of C3d-Binding Donor-Specific Anti-HLA Antibodies at Diagnosis of Humoral Rejection Predicts Renal Graft Loss

    Science.gov (United States)

    Sicard, Antoine; Ducreux, Stéphanie; Rabeyrin, Maud; Couzi, Lionel; McGregor, Brigitte; Badet, Lionel; Scoazec, Jean Yves; Bachelet, Thomas; Lepreux, Sébastien; Visentin, Jonathan; Merville, Pierre; Fremeaux-Bacchi, Véronique; Morelon, Emmanuel; Taupin, Jean-Luc; Dubois, Valérie

    2015-01-01

    Antibody-mediated rejection (AMR) is a major cause of kidney graft loss, yet assessment of individual risk at diagnosis is impeded by the lack of a reliable prognosis assay. Here, we tested whether the capacity of anti-HLA antibodies to bind complement components allows accurate risk stratification at the time of AMR diagnosis. Among 938 kidney transplant recipients for whom a graft biopsy was performed between 2004 and 2012 at the Lyon University Hospitals, 69 fulfilled the diagnosis criteria for AMR and were enrolled. Sera banked at the time of the biopsy were screened for the presence of donor-specific anti-HLA antibodies (DSAs) and their ability to bind C1q and C3d using flow bead assays. In contrast with C4d graft deposition, the presence of C3d-binding DSA was associated with a higher risk of graft loss (P<0.001). Despite similar trend, the difference did not reach significance with a C1q-binding assay (P=0.06). The prognostic value of a C3d-binding assay was further confirmed in an independent cohort of 39 patients with AMR (P=0.04). Patients with C3d-binding antibodies had worse eGFR and higher DSA mean fluorescence intensity. In a multivariate analysis, only eGFR<30 ml/min per 1.73 m2 (hazard ratio [HR], 3.56; 95% confidence interval [CI], 1.46 to 8.70; P=0.005) and the presence of circulating C3d-binding DSA (HR, 2.80; 95% CI, 1.12 to 6.95; P=0.03) were independent predictors for allograft loss at AMR diagnosis. We conclude that assessment of the C3d-binding capacity of DSA at the time of AMR diagnosis allows for identification of patients at risk for allograft loss. PMID:25125383

  8. Effective equine immunization protocol for production of potent poly-specific antisera against Calloselasma rhodostoma, Cryptelytrops albolabris and Daboia siamensis.

    Directory of Open Access Journals (Sweden)

    Sompong Sapsutthipas

    2015-03-01

    Full Text Available Snake envenomation has been estimated to affect 1.8 million people annually with about 94,000 deaths mostly in poor tropical countries. Specific antivenoms are the only rational and effective therapy for these cases. Efforts are being made to produce effective, affordable and sufficient antivenoms for these victims. The immunization process, which has rarely been described in detail, is one step that needs to be rigorously studied and improved especially with regard to the production of polyspecific antisera. The polyspecific nature of therapeutic antivenom could obviate the need to identify the culprit snake species. The aim of this study was to produce potent polyspecific antisera against 3 medically important vipers of Thailand and its neighboring countries, namely Cryptelytrops albolabris "White lipped pit viper" (CA, Calleoselasma rhodostoma "Malayan pit viper" (CR, and Daboia siamensis "Russell's viper" (DS. Four horses were immunized with a mixture of the 3 viper venoms using the 'low dose, low volume multi-site' immunization protocol. The antisera showed rapid rise in ELISA titers against the 3 venoms and reached plateau at about the 8th week post-immunization. The in vivo neutralization potency (P of the antisera against CA, CR and DS venoms was 10.40, 2.42 and 0.76 mg/ml, respectively and was much higher than the minimal potency limits set by Queen Soavabha Memorial Institute (QSMI. The corresponding potency values for the QSMI monospecific antisera against CA, CR and DS venoms were 7.28, 3.12 and 1.50 mg/ml, respectively. The polyspecific antisera also effectively neutralized the procoagulant, hemorrhagic, necrotic and nephrotoxic activities of the viper venoms. This effective immunization protocol should be useful in the production of potent polyspecific antisera against snake venoms, and equine antisera against tetanus, diphtheria or rabies.

  9. A new Pan African polyspecific antivenom developed in response to the antivenom crisis in Africa.

    Science.gov (United States)

    Laing, G D; Renjifo, J M; Ruiz, F; Harrison, R A; Nasidi, A; Gutierrez, J-M; Rowley, P D; Warrell, D A; Theakston, R D G

    2003-07-01

    Currently there is a crisis in the supply of antivenom for treatment of snake bite in sub-Saharan Africa. Commercial pressures have resulted in the reduction or even cessation of production of antivenom by European manufacturers while continued production of antivenom in Africa has been threatened by the privatisation of the only remaining company based in Africa. As a consequence, there has been an increase in snake bite morbidity and mortality in many African countries. Two Latin American antivenom manufacturers have agreed to produce antivenom suitable for Africa, using venoms from the species which are of the greatest medical importance in sub-Saharan Africa. Preclinical in vivo assays of neutralising potency demonstrated that a new Pan African antivenom produced in Colombia compared favourably with the existing commercial monospecific and polyspecific antivenoms. This new antivenom, and a similar product being manufactured in Costa Rica, are now candidates for clinical testing at an appropriate site in Africa. PMID:12893059

  10. A new DNA vaccine fused with the C3d-p28 induces a Th2 immune response against amyloid-beta*

    Institute of Scientific and Technical Information of China (English)

    Wanshu Guo; Sha Sha; Tongzi Jiang; Xiaona Xing; Yunpeng Cao

    2013-01-01

    To enhance anti-amyloid-beta (Aβ) antibody generation and induce a Th2 immune response, we constructed a new DNA vaccine p(Aβ3-10 )10-C3d-p28.3 encoding ten repeats of Aβ3-10 and three copies of C3d-p28 as a molecular adjuvant. In this study, we administered this adjuvant intramus-cularly to female C57BL/6J mice at 8-10 weeks of age. Enzyme linked immunosorbent assay was used to detect the titer of serum anti-Aβ antibody, isotypes, and cytokines in splenic T cel s. A 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was used to detect the prolifera-tion rate of splenic T cel s. Brain sections from a 12-month-old APP/PS1 transgenic mouse were used for detecting the binding capacities of anti-Aβ antibodies to Aβ plaques. The p(Aβ3-10)10-C3d-p28.3 vaccine induced high titers of anti-amyloid-βantibodies, which bound to Aβplaques in APP/PS1 transgenic mouse brain tissue, demonstrating that the vaccine is effective against plaques in a mouse model of Alzheimer’s disease. Moreover, the vaccine elicited a pre-dominantly IgG1 humoral response and low levels of interferon-γ in ex vivo cultured splenocytes, indicating that the vaccine could shift the cel ular immune response towards a Th2 phenotype. This indicated that the vaccine did not elicit a detrimental immune response and had a favorable safety profile. Our results indicate that the p(Aβ3-10)10-C3d-p28.3 vaccine is a promising immunothera-peutic option for Aβvaccination in Alzheimer’s disease.

  11. Studies on image quality, high contrast resolution and dose for the axial skeleton and limbs with a new, dedicated CT system (ISO-C-3D)

    International Nuclear Information System (INIS)

    Purpose: Evaluation of 3D-CT imaging of the axial skeleton and different joints of the lower and upper extremities with a new dedicated CT system (ISO-C-3D) based on a mobile isocentric C-arm image amplifier. Material and Methods: 27 cadaveric specimes of different joints of the lower and upper extremities and of the spinal column were examined with 3D-CT imaging (ISO-C-3d). All images were evaluated by 3 radiologists for image quality using a semiquantitative score (score value 1: poor quality; score value 4: excellent quality). In addition, dose measurements and measurements of high contrast resolution were performed in comparison to conventional and low-dose spiral CT using a high contrast phantom (Catphan, Phantom Laboratories). Results: Adequate image quality (mean score values 3-4) could be achieved with an applied dose comparable to low-dose CT in smaller joints such as wrist, elbow, ankle and knee. A remarkably inferior image quality resulted in imaging of the hip, lumbar and thoracic spine (mean score values 2-3) in spite of almost doubling the dose (dose increased by 85 percent). The image quality of shoulder examinations was insufficient (mean score value 1). Phantom studies showed a high-contrast resolution comparable to helical CT in the xy-axis (9 lp/cm). Conclusion: Preliminary results show, that image quality of C-arm-based CT-imaging (ISO-C-3D) seems to be adequate in smaller joints. ISO-C-3D images of the hip and axial skeleton show a decreased image quality, which does not seem to be sufficient for diagnosing subtle fractures. (orig.)

  12. Intrathecal, polyspecific antiviral immune response in oligoclonal band negative multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Isabel Brecht

    Full Text Available BACKGROUND: Oligoclonal bands (OCB are detected in the cerebrospinal fluid (CSF in more than 95% of patients with multiple sclerosis (MS in the Western hemisphere. Here we evaluated the intrathecal, polyspecific antiviral immune response as a potential diagnostic CSF marker for OCB-negative MS patients. METHODOLOGY/PRINCIPAL FINDINGS: We tested 46 OCB-negative German patients with paraclinically well defined, definite MS. Sixteen OCB-negative patients with a clear diagnosis of other autoimmune CNS disorders and 37 neurological patients without evidence for autoimmune CNS inflammation served as control groups. Antibodies against measles, rubella, varicella zoster and herpes simplex virus in paired serum and CSF samples were determined by ELISA, and virus-specific immunoglobulin G antibody indices were calculated. An intrathecal antibody synthesis against at least one neurotropic virus was detected in 8 of 26 (31% patients with relapsing-remitting MS, 8 of 12 (67% with secondary progressive MS and 5 of 8 (63% with primary progressive MS, in 3 of 16 (19% CNS autoimmune and 3 of 37 (8% non-autoimmune control patients. Antibody synthesis against two or more viruses was found in 11 of 46 (24% MS patients but in neither of the two control groups. On average, MS patients with a positive antiviral immune response were older and had a longer disease duration than those without. CONCLUSION: Determination of the intrathecal, polyspecific antiviral immune response may allow to establish a CSF-supported diagnosis of MS in OCB-negative patients when two or more of the four virus antibody indices are elevated.

  13. Stable isotope ratios suggest limited trophic importance of seagrasses for invertebrate consumers from Malagasy tropical polyspecific seagrass meadows

    OpenAIRE

    Michel, Loïc; Wang, Haolin; Frederich, Bruno; Lavitra, Thierry; Lepoint, Gilles

    2015-01-01

    Polyspecific seagrass meadows are of critical ecological importance in tropical coastal zones. These ecosystems provide a wide range of socio-economical services to local populations. Meadows however undergo multiple threats linked to human activities (increased nutrient input, overfishing, invertebrate overharvesting, etc.). It is currently difficult to assess how seagrass meadows could respond to anthropogenic impacts due to poor knowledge of their functional ecology. Here, stable isoto...

  14. Circadian and diurnal variation of circulating immune complexes, complement-mediated solubilization, and the complement split product C3d in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Petersen, Ivan; Baatrup, Gunnar; Brandslund, I;

    1986-01-01

    Nine patients with active classical rheumatoid arthritis (ARA criteria) were studied with reference to circadian variation of immunological and clinical parameters. Complement-mediated solubilization (CMS) of immune complexes (IC) and the level of circulating IC were found to be inversely related...... with low CMS and increased IC levels in the morning, and vice versa in the afternoon. Bed rest and exercise did not influence these fluctuations. The C3d concentration in plasma was increased but showed no diurnal or circadian periodic fluctuations when the levels were corrected for fluctuations in plasma...

  15. Candida albicans and Candida stellatoidea, in contrast to other Candida species, bind iC3b and C3d but not C3b.

    OpenAIRE

    Heidenreich, F; Dierich, M.P.

    1985-01-01

    It was demonstrated that complement-coated sheep erythrocytes bind to Candida albicans cells grown in serum-free RPMI 1640 medium. Testing of purified complement components proved that iC3b and C3d were responsible for the reaction, whereas C3b and C3b-H reacted only slightly if at all. Binding occurred only to C. albicans and C. stellatoidea, not to other species pathogenic to humans. There was evidence of a lectinlike nature of the effect.

  16. Enhancement of anti-DIII antibodies by the C3d derivative P28 results in lower viral titers and augments protection in mice

    Directory of Open Access Journals (Sweden)

    Mehlhop Erin

    2010-05-01

    Full Text Available Abstract Antibodies generated against West Nile virus (WNV during infection are essential for controlling dissemination. Recent studies have demonstrated that epitopes in all three domains of the flavivirus envelope protein (E are targets for neutralizing antibodies, with determinants in domain III (DIII eliciting antibodies with strong inhibitory properties. In order to increase the magnitude and quality of the antibody response against the WNV E protein, DNA vaccines with derivatives of the WNV E gene (full length E, truncated E, or DIII region, some in the context of the pre-membrane [prM] gene were conjugated to the molecular adjuvant P28. The P28 region of the complement protein C3d is the minimum CR2-binding domain necessary for the adjuvant activity of C3d. Delivery of DNA-based vaccines by gene gun and intramuscular routes stimulated production of IgG antibodies against the WNV DIII region of the E protein. With the exception of the vaccine expressing prM/E given intramuscularly, only mice that received DNA vaccines by gene gun produced protective neutralizing antibody titers (FRNT80 titer >1/40. Correspondingly, mice vaccinated by the gene gun route were protected to a greater level from lethal WNV challenge. In general, mice vaccinated with P28-adjuvated vaccines produced higher IgG titers than mice vaccinated with non-adjuvanted vaccines.

  17. Detection of tibial condylar fractures using 3D imaging with a mobile image amplifier (Siemens ISO-C-3D): Comparison with plain films and spiral CT

    International Nuclear Information System (INIS)

    Purpose: To analyze a prototype mobile C-arm 3D image amplifier in the detection and classification of experimental tibial condylar fractures with multiplanar reconstructions (MPR). Method: Human knee specimens (n=22) with tibial condylar fractures were examined with a prototype C-arm (ISO-C-3D, Siemens AG), plain films (CR) and spiral CT (CT). The motorized C-arm provides fluoroscopic images during a 190 orbital rotation computing a 119 mm data cube. From these 3D data sets MP reconstructions were obtained. All images were evaluated by four independent readers for the detection and assessment of fracture lines. All fractures were classified according to the Mueller AO classification. To confirm the results, the specimens were finally surgically dissected. Results: 97% of the tibial condylar fractures were easily seen and correctly classified according to the Mueller AO classification on MP reconstruction of the ISO-C-3D. There is no significant difference between ISO-C and CT in detection and correct classification of fractures, but ISO-CD-3D is significant by better than CR. (orig.)

  18. Cutting edge: members of the Staphylococcus aureus extracellular fibrinogen-binding protein family inhibit the interaction of C3d with complement receptor 2.

    Science.gov (United States)

    Ricklin, Daniel; Ricklin-Lichtsteiner, Salome K; Markiewski, Maciej M; Geisbrecht, Brian V; Lambris, John D

    2008-12-01

    Staphylococcus aureus expresses a highly diversified arsenal of immune evasion proteins, many of which target the complement system. The extracellular fibrinogen-binding protein (Efb) and the Efb homologous protein (Ehp) have previously been demonstrated to bind to C3 and inhibit complement activation and amplification. In this study we present the first evidence that Efb and Ehp are also capable of inhibiting the interaction of C3d with complement receptor 2 (CR2), which plays an important role in B cell activation and maturation. The C-terminal domain of Efb efficiently blocked this interaction both in surface plasmon resonance-based competition studies and cellular assays and prevented the CR2-mediated stimulation of B cells. Furthermore, analyses of the available structural data were consistent with a molecular mechanism that reflects both steric and electrostatic effects on the C3d-CR2 interaction. Our study therefore suggests that S. aureus may disrupt both the innate and adaptive immune responses with a single protein module. PMID:19017934

  19. Polyspecific associations between squirrel monkeys (Saimiri sciureus) and other primates in eastern Amazonia.

    Science.gov (United States)

    Pinheiro, Tatyana; Ferrari, Stephen F; Lopes, Maria Aparecida

    2011-11-01

    One of the most common types of polyspecific association observed in Neotropical primate communities is that between squirrel monkeys (Saimiri) and capuchins (Cebus). The present study focused on association patterns in two Saimiri sciureus groups in eastern Brazilian Amazonia, between March and October, 2009. The associations were analyzed in terms of the species involved, the degree of association, and niche breadth and overlap. The study involved two S. sciureus groups (B4 and GI) on the right and left bank of the Tocantins River, respectively, within the area of the Tucuruí reservoir in southeastern Pará. Relations between species were classified as associations (individuals within 50 m and moving in the same direction), and encounters (individuals within 50 m and no coordinated movement). Group B4 was in association with Cebus apella during 100% of monitoring, and with Chiropotes satanas in 20.2%. By contrast, Group GI associated with Cebus 54.8% of the time, and with Chiropotes utahickae 2.5%. Encounters with Alouatta belzebul and Saguinus niger were recorded at both sites, with Aotus azarae and Dasyprocta prymnolopha at B4, and with Callicebus moloch, Dasyproct aleporina, Mazama gouazoubira, and Nasua nasua at GI. Overall, Saimiri had a broader niche than Cebus in terms of vertical spacing and diet, but not for substrate use. This pattern did not appear to be affected by association. While group GI spent significantly (P foraging patterns at the two sites, and the varying potential benefits of association for Saimiri. PMID:21809365

  20. Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding

    Energy Technology Data Exchange (ETDEWEB)

    Aller, Stephen G.; Yu, Jodie; Ward, Andrew; Weng, Yue; Chittaboina, Srinivas; Zhuo, Rupeng; Harrell, Patina M.; Trinh, Yenphuong T.; Zhang, Qinghai; Urbatsch, Ina L.; Chang, Geoffrey; (Scripps); (TTU)

    2009-04-22

    P-glycoprotein (P-gp) detoxifies cells by exporting hundreds of chemically unrelated toxins but has been implicated in multidrug resistance (MDR) in the treatment of cancers. Substrate promiscuity is a hallmark of P-gp activity, thus a structural description of poly-specific drug-binding is important for the rational design of anticancer drugs and MDR inhibitors. The x-ray structure of apo P-gp at 3.8 angstroms reveals an internal cavity of -6000 angstroms cubed with a 30 angstrom separation of the two nucleotide-binding domains. Two additional P-gp structures with cyclic peptide inhibitors demonstrate distinct drug-binding sites in the internal cavity capable of stereoselectivity that is based on hydrophobic and aromatic interactions. Apo and drug-bound P-gp structures have portals open to the cytoplasm and the inner leaflet of the lipid bilayer for drug entry. The inward-facing conformation represents an initial stage of the transport cycle that is competent for drug binding.

  1. 重组乳酸杆菌Lb.hCGβ-C3d3经鼻腔免疫BALB/c小鼠的抗生育潜能%The anti-fertility potential of inoculation via nose with recombinant live Lactobacilli of Lb.hCGβ-C3d3

    Institute of Scientific and Technical Information of China (English)

    王健理; 姚晓英; 李大金

    2011-01-01

    目的:探讨表达hCGβ-C3d3融合蛋白的重组乳酸杆菌避孕疫苗经鼻腔黏膜接种BALB/c小鼠及其抗生育潜能.方法:用野生型乳酸杆菌Lb.及重组乳酸杆菌Lb.hCGβ和Lb.hCGβ-C3d3 以两种剂量(109个和1010个)经鼻腔滴注接种6~8周龄雌性BALB/c小鼠.3周后用相同剂量加强免疫一次.于初次免疫后的第6、7、8周收集血清,分别培养MLTC-1、BeWo细胞;化学发光法检测培养上清中孕酮或hCGβ水平;免疫荧光观察抗血清处理后BeWo细胞的融合情况.结果:用1010个Lb.hCGβ-C3d3滴鼻免疫BALB/c小鼠产生的抗血清能显著抑制hCG刺激MLTC-1分泌孕酮,明显抑制BeWo细胞分泌hCGβ及细胞融合.结论:重组乳酸杆菌活疫苗Lb.hCGβ-C3d3经鼻腔接种诱导的hCGβ抗体可拮抗hCGβ生物学功能,并干扰滋养细胞功能,因此具有抗生育潜能.%0bjective :To evaluate the anti-fertility of potential by inoculation via nose with the recom binant live Lactobacilli expressing hCGβ-C3d3 fusion protein.Methods :Female BALB/cmie were inmunized with 1010,109 Lb,Lb.hCGβor Lb .hCGβ-C3d3,respectively,via nose .The antrserum was collected respectively in the 6-8th week after the primary inmunization M LTC-1and BeW o cell line were respectively treated with the anti-serum ,and then the supematant was recovered ,respective]y .Progesterone and hCGβ in the supematent were detemined by Chem olum inescence assay .Fusion of the BeW o cells was investigated by inmunofluorescence microscopy. Results :The anti-serum induced by the Lb. hCGβ-C3d3 inoculation with the dose of 1010 could significantly inhibit the progesterone production in MLTC-1 cells via neuttalizng hCG bioactivity ,and suppress the hCGβ secretion and fusion in vitro of BeW o cell line .Conclusion :Lb.hCGβ-C3d3 live Lactobacilli are effective in blocking hCG bioactivity,which appears anti-fertilily potential.

  2. A structural basis for Staphylococcal complement subversion: X-ray structure of the complement-binding domain of Staphylococcus aureus protein Sbi in complex with ligand C3d

    OpenAIRE

    Clark, E. A.; Crennell, S.; Upadhyay, A.; Zozulya, A. V.; Mackay, J. D.; Svergun, D.I.; Bagby, S; van den Elsen, J. M.

    2011-01-01

    The structure of the complement-binding domain of Staphylococcus aureus protein Sbi (Sbi-IV) in complex with ligand C3d is presented. The 1.7 Å resolution structure reveals the molecular details of the recognition of thioester-containing fragment C3d of the central complement component C3, involving interactions between residues of Sbi-IV helix α2 and the acidic concave surface of C3d. The complex provides a structural basis for the binding preference of Sbi for native C3 over C3b and explain...

  3. Contribution of C3d-P28 repeats to enhancement of immune responses against HBV-preS2/S induced by gene immunization

    Institute of Scientific and Technical Information of China (English)

    Li-Xin Wang; Wei Xu; Qing-Dong Guan; Yi-Wei Chu; Ying Wang; Si-Dong Xiong

    2004-01-01

    AIM: To investigate whether P28 derived from C3d can enhance the immune response to HBV-preS2/S induced by directly injection of naked plasmids containing variable repeats of P28 and HBV-preS2/S in fusion form.METHODS: One to four copies of C3d-P28 coding gene,amplified by PCR and modified by restriction endonucleases digestion, were subcloned into a eukaryotic expression vector pVAON33 to construct pVAON33-P28, pVAON33-P28.2, pVAON33-P28.3 and pVAON33-P28.4 (pVAON33-P28.[1-4]). HBV-preS2/S coding sequence was then introduced into the pVAON33-P28.[1-4] and identified by both PCR and DNA sequencing. BALB/c mice were primed by intramuscular gene immunization with 100 μg different recombinant plasmids on day 0 and were boosted by subcutaneous inoculation with HBsAg protein (1 μg) 12wk post-priming. The levels and avidity of specific IgG in sera collected at the indicated times from each group were determined by ELISA and NaSCN-displacement ELISA,respectively.RESULTS: HBsAg specific antibody response was elicited in groups primed with plasmids pVAON33-S2/S-P28.[1-4]and pVAON33-S2/S. However, the response against HBsAg in the groups primed with pVAON33-S2/S-P28.[1-4] was significantly higher than that in pVAON33-S2/S group, the highest level of the specific antibody response was observed in the groups primed with pVAON33-S2/S-P28.4 (P<0.01).After secondary immunization with specific antigen, the acceleration of antibody levels was significantly higher and faster in the mice primed with DNA expressing preS2/S-P28 fusions than that with DNA expressing preS2/S only (P<0.05).Interestingly, mice primed with DNA expressing preS2/SP28.4 fusions maintained the highest levels of anti-HBs antibodies in all animals. The avidity assay showed that the avidity index (AI) collected at 18 wk from mice primed with pVAON33-S2/S-P28.3 and pVAON33-S2/S-P28.4 were significantly higher than that from preS2/S-DNA vaccinated mice (P<0.01).CONCLUSION: Different repeats of C3d-P28 can

  4. Role of a Hydrophobic Pocket in Polyamine Interactions with the Polyspecific Organic Cation Transporter OCT3.

    Science.gov (United States)

    Li, Dan C; Nichols, Colin G; Sala-Rabanal, Monica

    2015-11-13

    Organic cation transporter 3 (OCT3, SLC22A3) is a polyspecific, facilitative transporter expressed in astrocytes and in placental, intestinal, and blood-brain barrier epithelia, and thus elucidating the molecular mechanisms underlying OCT3 substrate recognition is critical for the rational design of drugs targeting these tissues. The pharmacology of OCT3 is distinct from that of other OCTs, and here we investigated the role of a hydrophobic cavity tucked within the translocation pathway in OCT3 transport properties. Replacement of an absolutely conserved Asp by charge reversal (D478E), neutralization (D478N), or even exchange (D478E) abolished MPP(+) uptake, demonstrating this residue to be obligatory for OCT3-mediated transport. Mutations at non-conserved residues lining the putative binding pocket of OCT3 to the corresponding residue in OCT1 (L166F, F450L, and E451Q) reduced the rate of MPP(+) transport, but recapitulated the higher sensitivity pharmacological profile of OCT1. Thus, interactions of natural polyamines (putrescine, spermidine, spermine) and polyamine-like potent OCT1 blockers (1,10-diaminodecane, decamethonium, bistriethylaminodecane, and 1,10-bisquinuclidinedecane) with wild-type OCT3 were weak, but were significantly potentiated in the mutant OCT3s. Conversely, a reciprocal mutation in OCT1 (F161L) shifted the polyamine-sensitivity phenotype toward that of OCT3. Further analysis indicated that OCT1 and OCT3 can recognize essentially the same substrates, but the strength of substrate-transporter interactions is weaker in OCT3, as informed by the distinct makeup of the hydrophobic cleft. The residues identified here are key contributors to both the observed differences between OCT3 and OCT1 and to the mechanisms of substrate recognition by OCTs in general.

  5. A Newly Cloned ClC-3 Isoform, ClC-3d, as well as ClC-3a Mediates Cd2+-Sensitive Outwardly Rectifying Anion Currents

    Directory of Open Access Journals (Sweden)

    Toshiaki Okada

    2014-02-01

    Full Text Available Background: ClC-3, a member of the ClC family, is predicted to have six isoforms, ClC-3a to -3f, with distinct N- and C-terminal amino acid sequences. There have been conflicting reports on the properties of ClC-3a (also known as the N-terminal short form of ClC-3 and ClC-3b (the N-terminal long form of ClC-3 as plasmalemmal Cl- channels. Meanwhile, little is known about other isoforms. The amino acid sequence of ClC-3d (a C-terminal variant of the short form listed in the NCBI database was derived from the genomic sequence, but there has been no experimental evidence for the mRNA. Methods: PCR-cloning was made to obtain the full coding region of ClC-3d from mouse liver. Its molecular expression on the plasma membrane was microscopically examined in HEK293T cells transfected with GFP-tagged ClC-3d. Its functional plasmalemmal expression and the properties of currents were studies by whole-cell recordings in the cells transfected with ClC-3d. Results: The cloned ClC-3d was found to be the only isoform which has an N-terminal amino acid sequence identical to ClC-3a. When introduced into HEK293T cells, a minor fraction of exogenous ClC-3d proteins was detected at the plasma membrane, and activation of anion currents was observed at neutral pH under normotonic conditions. The properties of ClC-3d currents were found to be shared by ClC-3a-mediated currents. Also, both ClC-3d and -3a currents were found to be sensitive to Cd2+. ClC-3d overexpression never affected the endogenous activity of acid- or swelling-activated anion channels. Conclusion: We thus conclude that plasmalemmal ClC-3d, like ClC-3a, mediates Cd2+-sensitive outwardly rectifying anion currents and that ClC-3d is distinct from the molecular entities of acid- and volume-sensitive anion channels.

  6. Upgrading and Engineering Application Baseed on the C3D-SBP Equipment that Designed for Deep Sea Survey%基于深海作业设备C3D-SBP的升级改造与工程应用

    Institute of Scientific and Technical Information of China (English)

    梁春江; 岳鹏

    2015-01-01

    该文针对深海海底管缆搜索定位及海底地层地貌勘探任务需求,对已有C3D-SBP拖鱼系统进行升级改造,分别对该设备通信硬件、供电线路、连接电缆、软件源代码、USBL、测线进行改装设计.为配合该升级设备在工程中的应用,分别对作业过程中的原始数据资料判断提取技术、原始数据处理与分析技术、释放与回收技术进行相应调整改进.最终形成了一整套适用于深海海底管缆调查和地层地貌综合调查的应用系统升级改造方案.实际工程应用证明该改造方案可行,并带来直接经济效益和间接经济效益,为同类设备的升级改造与应用推广提供了参考,拓展了深海海底管缆和地层地貌调查的技术手段.%As for missions of search and positioning of deep-sea submarine pipe line and ocean exploration, the conventional way with low operation efficiency and high cost, already cannot meet the requirement of the engineering practice. With the practical application of deep investigation project as the research background, through the analysis of the upgrade requirements of existing equipment C3D-SBP, modify and design C3D-SBP communications hardware equipment, power lines, connecting cable, software source code, USBL, line detecting respectively, then study and design a set of C3D-SBP equipment upgrade scheme; To meet the requirement of the application of upgraded equipment in engineering, design and improve the original data judging and extraction technology, the original data processing and analysis technology, releasing and recycling technology of modified C3D-SBP equipment in the process of operation, and set up a set of system design program suitable for deep-sea submarine cables and geomorphic comprehensive survey application; By the feedback information of engineering application, summarize the innovation points of upgraded C3D-SBP equipment, as well as the direct and indirect economic benefit, which

  7. Role of acetylcholine and polyspecific cation transporters in serotonin-induced bronchoconstriction in the mouse

    Directory of Open Access Journals (Sweden)

    Koepsell Hermann

    2006-04-01

    Full Text Available Abstract Background It has been proposed that serotonin (5-HT-mediated constriction of the murine trachea is largely dependent on acetylcholine (ACh released from the epithelium. We recently demonstrated that ACh can be released from non-neuronal cells by corticosteroid-sensitive polyspecific organic cation transporters (OCTs, which are also expressed by airway epithelial cells. Hence, the hypothesis emerged that 5-HT evokes bronchoconstriction by inducing release of ACh from epithelial cells via OCTs. Methods We tested this hypothesis by analysing bronchoconstriction in precision-cut murine lung slices using OCT and muscarinic ACh receptor knockout mouse strains. Epithelial ACh content was measured by HPLC, and the tissue distribution of OCT isoforms was determined by immunohistochemistry. Results Epithelial ACh content was significantly higher in OCT1/2 double-knockout mice (42 ± 10 % of the content of the epithelium-denuded trachea, n = 9 than in wild-type mice (16.8 ± 3.6 %, n = 11. In wild-type mice, 5-HT (1 μM caused a bronchoconstriction that slightly exceeded that evoked by muscarine (1 μM in intact bronchi but amounted to only 66% of the response to muscarine after epithelium removal. 5-HT-induced bronchoconstriction was undiminished in M2/M3 muscarinic ACh receptor double-knockout mice which were entirely unresponsive to muscarine. Corticosterone (1 μM significantly reduced 5-HT-induced bronchoconstriction in wild-type and OCT1/2 double-knockout mice, but not in OCT3 knockout mice. This effect persisted after removal of the bronchial epithelium. Immunohistochemistry localized OCT3 to the bronchial smooth muscle. Conclusion The doubling of airway epithelial ACh content in OCT1/2-/- mice is consistent with the concept that OCT1 and/or 2 mediate ACh release from the respiratory epithelium. This effect, however, does not contribute to 5-HT-induced constriction of murine intrapulmonary bronchi. Instead, this activity involves 1 a non

  8. Evaluation of serum immonogiobulins (A,G,M and complement components (C3 d in Isfahan dental clinics patients with recurrent aphlus stomatitis

    Directory of Open Access Journals (Sweden)

    Ghalayani Isfahani P

    2000-06-01

    Full Text Available Recurrent aphtus stomatitis (RAS is an oral mucous lesion in patients with no other signs of disease. Investigators have always notified the role of immune system especially humoral immunity in aphtus immunopathogenesis. The aim of this case-controlled study was to measure amount of serum immonogiobulins (A,G,M and complement component (C3 d in patients with RAS and to evaluate any relation between differences in these factors and pathogenesis of RAS. Immonogiobulins (A,G,M and complement components (C3 Ci of 50 patients with RAS was measured using single radial immuno diffusion technique. The results were compared with immonogiobulins (A,G,M and complement components (C3 Cj of 50 healthy people whom were similar in age and sex with the patients group. Results showed that the patients group had higher level of IgA and IgM while serum lgG was similar in both groups. The C$ was lower in aphtus patients while no significant difference was found in amount of C,|. The sex had no significant effect on serum level of measured factors. From the results it can be concluded that the humoral immunity reaction has an important role in immunopathogenesis of RAS. This humoral response might accurse as a result of cellular immunity reaction.

  9. TISSUE DISTRIBUTION OF THE C3D/EBV-RECEPTOR - CD21 MONOCLONAL-ANTIBODIES REACTIVE WITH A VARIETY OF EPITHELIAL-CELLS, MEDULLARY THYMOCYTES, AND PERIPHERAL T-CELLS

    NARCIS (Netherlands)

    TIMENS, W; BOES, A; VOS, H; POPPEMA, S

    1991-01-01

    The CD21 antigen has been described to represent CR2, the receptor for the complement fragment C3d and also the receptor for the Epstein-Barr virus (EBV). Monoclonal antibodies B2, HB5, and B-ly4 belong to the CD21 cluster, recognizing different epitopes of the CD21-molecule. Immunohistology of lymp

  10. Preclinical evaluation of three polyspecific antivenoms against the venom of Echis ocellatus: Neutralization of toxic activities and antivenomics.

    Science.gov (United States)

    Calvete, Juan J; Arias, Ana Silvia; Rodríguez, Yania; Quesada-Bernat, Sarai; Sánchez, Laura V; Chippaux, Jean Philippe; Pla, Davinia; Gutiérrez, José María

    2016-09-01

    Snakebite envenoming has a heavy burden in the public health in sub-Saharan Africa. The viperid species Echis ocellatus (carpet viper or saw-scaled viper) is the medically most important snake in the savannahs of western sub-Saharan Africa. Several antivenoms are being distributed and used in this region for the treatment of envenomings by E. ocellatus, but the preclinical efficacy of some of these antivenoms has not been assessed. The present study evaluated the preclinical efficacy against E. ocellatus venom of three polyspecific antivenoms: (a) Snake Venom Antiserum (Pan Africa), manufactured by Premium Serums and Vaccines (India); (b) Snake Venom Antiserum (Africa), manufactured by VINS Bioproducts (India); and (c) Antivipmyn(®) Africa, manufactured by Instituto Bioclon (Mexico). Antivenomics analysis revealed the ability of the three antivenoms to immunocapture the majority of components of the venoms of E. ocellatus from Cameroon, Nigeria and Mali, although their maximal immunocapturing capability varied. Bioclon and Premium Serums antivenoms were effective in the neutralization of lethal, hemorrhagic and in vitro coagulant activities of the venom of E. ocellatus from Cameroon, albeit with different potencies. VINS antivenom neutralized hemorrhagic activity of this venom, but failed to neutralize lethality at the highest antivenom dose tested, and had a low neutralizing efficacy against in vitro coagulant effect. PMID:27377229

  11. Foot-and-Mouth Disease Virus neutralizing antibodies production induced by pcDNA3 and Sindbis virus based plasmid encoding FMDV P1-2A3C3D in swine.

    OpenAIRE

    Dory, Daniel; Rémond, Michelle; Béven, Véronique; Cariolet, Roland; Zientara, Stephan; Jestin, André

    2009-01-01

    International audience DNA vaccination against Foot-and-Mouth Disease Virus (FMDV) is an attractive and alternative strategy to the use of classical inactivated viral vaccines. The injection of a pcDNA3.1-based DNA vaccine encoding for FMDV P1-2A3C3D and GM-CSF proteins had previously been shown to induce the production of neutralizing antibodies against FMDV and partially protect swine against an experimental challenge. Based on the induction of FMDV humoral immune responses, the aim of t...

  12. Epstein-Barr virus/complement fragment C3d receptor (CR2) reacts with p53, a cellular antioncogene-encoded membrane phosphoprotein: detection by polyclonal anti-idiotypic anti-CR2 antibodies.

    OpenAIRE

    Barel, M; Fiandino, A; Lyamani, F; Frade, R

    1989-01-01

    Epstein-Barr virus and the C3d fragment of the third component of complement are specific extracellular ligands for complement receptor type 2 (CR2). However, intracellular proteins that react specifically with CR2 and are involved in post-membrane signals remain unknown. We recently prepared polyclonal anti-idiotypic anti-CR2 antibodies (Ab2) by using the highly purified CR2 molecule as original immunogen. We showed that Ab2 contained anti-idiotypic specificities that mimicked extracellular ...

  13. VH and VL Domains of Polyspecific IgM and Monospecific IgG Antibodies Contribute Differentially to Antigen Recognition and Virus Neutralization Functions.

    Science.gov (United States)

    Pasman, Y; Kaushik, A K

    2016-07-01

    We analysed contributions of variable heavy (FdVH ) and variable light (FdVL ) domains in comparison to scFv (FdVH +FdVL ) of naturally occurring polyspecific bovine IgM with an exceptionally long CDR3H and an induced monospecific bovine herpes virus-1 (BoHV-1) neutralizing IgG1 antibody in the context of to antigen-binding site and antibody function. Various recombinant FdVH , FdVL and scFv were constructed and expressed in Pichia pastoris from the bovine IgM and IgG1 antibody encoding cDNA. The scFv1H12 showed polyspecific antigen binding similar to parent IgM antibody, though subtle differences, for example, higher thyroglobulin recognition. Such differences reflect influence of the constant region on the antigen-binding site configuration. Unlike, variable light domain FdVL 1H12, the variable heavy domain FdVH 1H12 alone recognized multiple antigens that differed from the recognition pattern of scFv1H12 (FdVH +FdVL ) and the parent IgM antibody. Nonetheless, role of FdVL 1H12 in providing structural support to FdVH in antigen recognition is noted, apart from its intrinsic antigen recognition ability. Surface plasmon resonance analysis revealed low to moderate affinity of scFv1H12 to IgG antigen. By contrast, the individual FdVH 073 and FdVL 074, originating from induced BoHV-1 neutralizing IgG1 antibody, recognized target epitope on BoHV-1 weakly when compared to FdVH +FdVL (scFv3-18L). Interestingly, both the FdVH and FdVL domains of induced IgG antibody are required to achieve BoHV-1 neutralization. To conclude, there exist subtle functional differences in the contribution of FdVH and FdVL to antigen-binding site generation of polyspecific IgM and monospecific IgG antibodies relevant to antigen recognition and virus neutralization functions.

  14. Toxicity of Bothrops sp snake venoms from Ecuador and preclinical assessment of the neutralizing efficacy of a polyspecific antivenom from Costa Rica.

    Science.gov (United States)

    Laines, Johana; Segura, Álvaro; Villalta, Mauren; Herrera, María; Vargas, Mariángela; Alvarez, Gladys; Gutiérrez, José María; León, Guillermo

    2014-09-01

    The toxicological profile of the venoms of the snakes Bothrops asper and Bothrops atrox from Ecuador was investigated, together with the venom of a population of B. asper formerly classified as 'Bothrops xanthogrammus'. The three venoms exerted lethal, hemorrhagic, myotoxic, coagulant and defibrinogenating effects, in agreement with the characteristic toxicological profile of Bothrops sp venoms. A polyspecific antivenom (bothropic-crotalic-lachesic) manufactured in Costa Rica was assessed for its preclinical efficacy against the toxic activities of these Ecuadorian venoms. Antivenom was effective in the neutralization of the five activities tested in the three venoms. These observations are in agreement with previous reports on the extensive cross-reactivity and paraspecific neutralization of antivenoms manufactured in Latin America against the venoms of Bothrops sp snakes. PMID:24950051

  15. Design and development of TT30, a novel C3d-targeted C3/C5 convertase inhibitor for treatment of human complement alternative pathway-mediated diseases.

    Science.gov (United States)

    Fridkis-Hareli, Masha; Storek, Michael; Mazsaroff, Istvan; Risitano, Antonio M; Lundberg, Ante S; Horvath, Christopher J; Holers, V Michael

    2011-10-27

    To selectively modulate human complement alternative pathway (CAP) activity implicated in a wide range of acute and chronic inflammatory conditions and to provide local cell surface and tissue-based inhibition of complement-induced damage, we developed TT30, a novel therapeutic fusion protein linking the human complement receptor type 2 (CR2/CD21) C3 fragment (C3frag = iC3b, C3dg, C3d)-binding domain with the CAP inhibitory domain of human factor H (fH). TT30 efficiently blocks ex vivo CAP-dependent C3frag accumulation on activated surfaces, membrane attack complex (MAC) formation and hemolysis of RBCs in a CR2-dependent manner, and with a ∼ 150-fold potency gain over fH, without interference of C3 activation or MAC formation through the classic and lectin pathways. TT30 protects RBCs from hemolysis and remains bound and detectable for at least 24 hours. TT30 selectively inhibits CAP in cynomolgus monkeys and is bioavailable after subcutaneous injection. Using a unique combination of targeting and effector domains, TT30 controls cell surface CAP activation and has substantial potential utility for the treatment of human CAP-mediated diseases. PMID:21860027

  16. Design and development of TT30, a novel C3d-targeted C3/C5 convertase inhibitor for treatment of human complement alternative pathway-mediated diseases.

    Science.gov (United States)

    Fridkis-Hareli, Masha; Storek, Michael; Mazsaroff, Istvan; Risitano, Antonio M; Lundberg, Ante S; Horvath, Christopher J; Holers, V Michael

    2011-10-27

    To selectively modulate human complement alternative pathway (CAP) activity implicated in a wide range of acute and chronic inflammatory conditions and to provide local cell surface and tissue-based inhibition of complement-induced damage, we developed TT30, a novel therapeutic fusion protein linking the human complement receptor type 2 (CR2/CD21) C3 fragment (C3frag = iC3b, C3dg, C3d)-binding domain with the CAP inhibitory domain of human factor H (fH). TT30 efficiently blocks ex vivo CAP-dependent C3frag accumulation on activated surfaces, membrane attack complex (MAC) formation and hemolysis of RBCs in a CR2-dependent manner, and with a ∼ 150-fold potency gain over fH, without interference of C3 activation or MAC formation through the classic and lectin pathways. TT30 protects RBCs from hemolysis and remains bound and detectable for at least 24 hours. TT30 selectively inhibits CAP in cynomolgus monkeys and is bioavailable after subcutaneous injection. Using a unique combination of targeting and effector domains, TT30 controls cell surface CAP activation and has substantial potential utility for the treatment of human CAP-mediated diseases.

  17. Modeling the presentation of C3d-coated antigen by B lymphocytes: enhancement by CR1/2-BCR co-ligation is selective for the co-ligating antigen.

    Science.gov (United States)

    Prechl, József; Baiu, Dana C; Horváth, Attila; Erdei, Anna

    2002-03-01

    We have used a set of single-chain variable fragment antibodies (sc) genetically fused with an influenza hemagglutinin-derived peptide as a means to investigate the role of CR1 and CR2 in antigen presentation by B cells. When incubated with the B cell lymphoma 2PK3, peptide-containing sc specific for either CR1 or CR1/2 mediated activation of the hemagglutinin peptide-specific T cell line IP-12-7, as assessed by IL-2 production. Efficient presentation was dependent on the binding of the constructs to CR1/2, implying that receptor-mediated endocytosis is responsible for the effect. Cross-linkage of CR1/2 or CD19 by mAb did not increase the extent of T cell activation. However, when CR1/2 was co-ligated with the BCR--using either polyclonal goat anti-mouse IgG or recombinant protein LA--the antigen concentration required to activate T cells decreased by two orders of magnitude. Moreover, this enhancement was selective for the antigen included in these complexes and did not affect the presentation of a free peptide or of antigen bound to CR1/2 excluded from the complexes. These results suggest that B cells may bind various C3d-coated antigens at a time, but only the one which reacts with the BCR will be processed with high efficiency. This mechanism may ensure the specificity of cognate T cell help. PMID:11867560

  18. Polyspecific associations of Cercopithecus campbelli and C. petaurista with C. diana: what are the costs and benefits?

    Science.gov (United States)

    Buzzard, Paul J

    2010-10-01

    Polyspecific associations (PSA) are common in many African primate communities, including the diurnal primates at Taï Forest, Côte d'Ivoire. In this paper I use data on the PSA of two forest guenons, Campbell's (Cercopithecus campbelli) and lesser spot-nosed monkeys (C. petaurista), with Diana monkeys (C. diana) and other primates to clarify interspecific relationships during 17 months including a 3-month low-fruit period. I analyzed association in relation to fruit availability and measured forest strata use for C. campbelli and C. petaurista when alone and in associations with and without C. diana. I also measured predator risk and reactions to potential predators. C. campbelli and C. petaurista had high association rates with C. diana monkeys, and fruit availability did not influence association rates. C. campbelli and C. petaurista used higher strata when in association with C. diana than when alone, but they used even higher strata when associated with other primates without C. diana. This suggested that C. diana competitively exclude C. campbelli and C. petaurista from higher strata. There were relatively large numbers of potential predators, and C. diana were usually the first callers to threatening stimuli, suggesting that antipredator benefits of association with C. diana outweighed the competitive costs. C. campbelli spent more time in association with C. diana than C. petaurista did and appeared to be more reliant on C. diana for antipredator benefits. C. petaurista were less reliant on C. diana because of a cryptic strategy and may have associated less in some months because of high chimpanzee (Pan troglodytes) presence. PMID:20535628

  19. Identification of a partial cDNA clone for the C3d/Epstein-Barr virus receptor of human B lymphocytes: homology with the receptor for fragments C3b and C4b of the third and fourth components of complement.

    OpenAIRE

    Weis, J J; Fearon, D T; Klickstein, L B; Wong, W. W.; Richards, S A; de Bruyn Kops, A; Smith, J. A.; Weis, J H

    1986-01-01

    Human complement receptor type 2 (CR2) is the B-lymphocyte receptor both for the C3d fragment of the third component of complement and for the Epstein-Barr virus. Amino acid sequence analysis of tryptic peptides of CR2 revealed a strong degree of homology with the human C3b/C4b receptor, CR1. This homology suggested that CR1 gene sequences could be used to detect the CR2 sequences at conditions of low-stringency hybridization. Upon screening a human tonsillar cDNA library with CR1 cDNA sequen...

  20. Identification of a partial cDNA clone for the C3d/Epstein-Barr virus receptor of human B lymphocytes: homology with the receptor for fragments C3b and C4b of the third and fourth components of complement.

    Science.gov (United States)

    Weis, J J; Fearon, D T; Klickstein, L B; Wong, W W; Richards, S A; de Bruyn Kops, A; Smith, J A; Weis, J H

    1986-08-01

    Human complement receptor type 2 (CR2) is the B-lymphocyte receptor both for the C3d fragment of the third component of complement and for the Epstein-Barr virus. Amino acid sequence analysis of tryptic peptides of CR2 revealed a strong degree of homology with the human C3b/C4b receptor, CR1. This homology suggested that CR1 gene sequences could be used to detect the CR2 sequences at conditions of low-stringency hybridization. Upon screening a human tonsillar cDNA library with CR1 cDNA sequences, two clones were identified that hybridized at low, but not at high, stringency. Redundant oligonucleotides specific for CR2 sequences were synthesized and used to establish that the two cDNA clones weakly hybridizing with the CR1 cDNA contained CR2 sequences. One of these CR2 cDNA clones hybridized to oligonucleotides derived from two distinct CR2 tryptic peptides, whereas the other, smaller cDNA clone hybridized to oligonucleotides derived from only one of the CR2 peptides. Nucleotide sequence analysis of the CR2 cDNA confirmed that the site of oligonucleotide hybridization was identical to that predicted from the peptide sequence, including flanking sequences not included within the oligonucleotide probes. The CR2-specific cDNA sequences identified a poly(A)+ RNA species of 5 kilobases in RNA extracted from human B cells but did not hybridize to any RNA obtained from the CR2-negative T-cell line HSB-2, thus confirming the appropriate size and tissue-specific distribution for the CR2 mRNA. The striking peptide sequence homology between CR2 and CR1 and the cross-hybridization of the CR2 cDNA with the CR1-specific sequences allow the placement of CR2 in a recently defined gene family of C3- and C4-binding proteins consisting of CR1, C4-binding protein, factor H, and now, CR2. PMID:3016712

  1. SHEAR WAVE SEISMIC STUDY COMPARING 9C3D SV AND SH IMAGES WITH 3C3D C-WAVE IMAGES

    Energy Technology Data Exchange (ETDEWEB)

    John Beecherl; Bob A. Hardage

    2004-07-01

    The objective of this study was to compare the relative merits of shear-wave (S-wave) seismic data acquired with nine-component (9-C) technology and with three-component (3-C) technology. The original proposal was written as if the investigation would be restricted to a single 9-C seismic survey in southwest Kansas (the Ashland survey), on the basis of the assumption that both 9-C and 3-C S-wave images could be created from that one data set. The Ashland survey was designed as a 9-C seismic program. We found that although the acquisition geometry was adequate for 9-C data analysis, the source-receiver geometry did not allow 3-C data to be extracted on an equitable and competitive basis with 9-C data. To do a fair assessment of the relative value of 9-C and 3-C seismic S-wave data, we expanded the study beyond the Ashland survey and included multicomponent seismic data from surveys done in a variety of basins. These additional data were made available through the Bureau of Economic Geology, our research subcontractor. Bureau scientists have added theoretical analyses to this report that provide valuable insights into several key distinctions between 9-C and 3-C seismic data. These theoretical considerations about distinctions between 3-C and 9-C S-wave data are presented first, followed by a discussion of differences between processing 9-C common-midpoint data and 3-C common-conversion-point data. Examples of 9-C and 3-C data are illustrated and discussed in the last part of the report. The key findings of this study are that each S-wave mode (SH-SH, SV-SV, or PSV) involves a different subsurface illumination pattern and a different reflectivity behavior and that each mode senses a different Earth fabric along its propagation path because of the unique orientation of its particle-displacement vector. As a result of the distinct orientation of each mode's particle-displacement vector, one mode may react to a critical geologic condition in a more optimal way than do the other modes. A conclusion of the study is that 9-C seismic data contain more rock and fluid information and more sequence and facies information than do 3-C seismic data; 9-C data should therefore be acquired in multicomponent seismic programs whenever possible.

  2. Photodissociation of the Propargyl (C3D3) Radicals at 248 nm and 193 nm

    Energy Technology Data Exchange (ETDEWEB)

    Neumark., D.M.; Crider, P.E.; Castiglioni, L.; Kautzman, K.K.

    2009-01-21

    The photodissociation of perdeuterated propargyl (D{sub 2}CCCD) and propynyl (D{sub 3}CCC) radicals was investigated using fast beam photofragment translational spectroscopy. Radicals were produced from their respective anions by photodetachment at 540 nm and 450 nm (below and above the electron affinity of propynyl). The radicals were then photodissociated by 248 nm or 193 nm light. The recoiling photofragments were detected in coincidence with a time- and position-sensitive detector. Three channels were observed: D{sub 2} loss, CD + C{sub 2}D{sub 2}, and CD{sub 3} + C{sub 2}. Obervation of the D loss channel was incompatible with this experiment and was not attempted. Our translational energy distributions for D{sub 2} loss peaked at nonzero translational energy, consistent with ground state dissociation over small (< 1 eV) exit barriers with respect to separated products. Translational energy distributions for the two heavy channels peaked near zero kinetic energy, indicating dissociation on the ground state in the absence of exit barriers.

  3. Laboratory Study of the Diagnostic Utility of the 3C/3D Line Ratio in Fe XVII

    Science.gov (United States)

    Brown, G. V.; Beiersdorfer, P.; Chen, H.; Chen, M., II; Reed, K. J.

    2002-01-01

    Fe XVII X-ray emission is present in a multitude of sources, such as the corona of the Sun, Capella, and Procyon. Two of the strongest lines observed in these spectra are the resonance and intercombination lines located at 15.01 and 15.26 A, respectively. As part of the laboratory astrophysics program at the electron beam ion traps EBIT-I & EBIT-II located at the Lawrence Livermore National Laboratory we have measured this line ratio for the case where the relative abundance of Fe XVI to Fe XVII is approx. 1. Our results show that an Fe XVI innershell satellite line coincides with the intercombination line and can significantly reduce the relative intensity, R, of the resonance to intercombination line. The fact that the apparent relative intensity of the resonance and intercombination line in Fe XVII is sensitive to the strength of an Fe XVI innershell satellite, and therefore, tho relative abundance of Fe XVI to Fe XVII, makes the line ratio a diagnostic of temperature, and explains the anomalously low ratios observed in the solar and stellar coronae.

  4. Targeted complement inhibition by C3d recognition ameliorates tissue injury without apparent increase in susceptibility to infection.

    Science.gov (United States)

    Atkinson, Carl; Song, Hongbin; Lu, Bo; Qiao, Fei; Burns, Tara A; Holers, V Michael; Tsokos, George C; Tomlinson, Stephen

    2005-09-01

    Previous studies indicate a pivotal role for complement in mediating both local and remote injury following ischemia and reperfusion of the intestine. Here, we report on the use of a mouse model of intestinal ischemia/reperfusion injury to investigate the strategy of targeting complement inhibition to sites of complement activation by linking an iC3b/C3dg-binding fragment of mouse complement receptor 2 (CR2) to a mouse complement-inhibitory protein, Crry. We show that the novel CR2-Crry fusion protein targets sites of local and remote (lung) complement activation following intestinal ischemia and reperfusion injury and that CR2-Crry requires a 10-fold lower dose than its systemic counterpart, Crry-Ig, to provide equivalent protection from both local and remote injury. CR2-Crry has a significantly shorter serum half-life than Crry-Ig and, unlike Crry-Ig, had no significant effect on serum complement activity at minimum effective therapeutic doses. Furthermore, the minimum effective dose of Crry-Ig significantly enhanced susceptibility to infection in a mouse model of acute septic peritonitis, whereas the effect of CR2-Crry on susceptibility to infection was indistinguishable from that of PBS control. Thus, compared with systemic inhibition, CR2-mediated targeting of a complement inhibitor of activation improved bioavailability, significantly enhanced efficacy, and maintained host resistance to infection. PMID:16127466

  5. Targeted complement inhibition by C3d recognition ameliorates tissue injury without apparent increase in susceptibility to infection

    OpenAIRE

    Atkinson, Carl; Song, Hongbin; Lu, Bo; Qiao, Fei; Burns, Tara A.; Holers, V. Michael; Tsokos, George C.; Tomlinson, Stephen

    2005-01-01

    Previous studies indicate a pivotal role for complement in mediating both local and remote injury following ischemia and reperfusion of the intestine. Here, we report on the use of a mouse model of intestinal ischemia/reperfusion injury to investigate the strategy of targeting complement inhibition to sites of complement activation by linking an iC3b/C3dg-binding fragment of mouse complement receptor 2 (CR2) to a mouse complement-inhibitory protein, Crry. We show that the novel CR2-Crry fusio...

  6. Targeted complement inhibition by C3d recognition ameliorates tissue injury without apparent increase in susceptibility to infection.

    Science.gov (United States)

    Atkinson, Carl; Song, Hongbin; Lu, Bo; Qiao, Fei; Burns, Tara A; Holers, V Michael; Tsokos, George C; Tomlinson, Stephen

    2005-09-01

    Previous studies indicate a pivotal role for complement in mediating both local and remote injury following ischemia and reperfusion of the intestine. Here, we report on the use of a mouse model of intestinal ischemia/reperfusion injury to investigate the strategy of targeting complement inhibition to sites of complement activation by linking an iC3b/C3dg-binding fragment of mouse complement receptor 2 (CR2) to a mouse complement-inhibitory protein, Crry. We show that the novel CR2-Crry fusion protein targets sites of local and remote (lung) complement activation following intestinal ischemia and reperfusion injury and that CR2-Crry requires a 10-fold lower dose than its systemic counterpart, Crry-Ig, to provide equivalent protection from both local and remote injury. CR2-Crry has a significantly shorter serum half-life than Crry-Ig and, unlike Crry-Ig, had no significant effect on serum complement activity at minimum effective therapeutic doses. Furthermore, the minimum effective dose of Crry-Ig significantly enhanced susceptibility to infection in a mouse model of acute septic peritonitis, whereas the effect of CR2-Crry on susceptibility to infection was indistinguishable from that of PBS control. Thus, compared with systemic inhibition, CR2-mediated targeting of a complement inhibitor of activation improved bioavailability, significantly enhanced efficacy, and maintained host resistance to infection.

  7. Epstein-Barr virus receptor of human B lymphocytes is the C3d receptor CR2.

    OpenAIRE

    Fingeroth, J D; Weis, J J; Tedder, T F; Strominger, J.L.; Biro, P A; D.T. Fearon

    1984-01-01

    Identity of the Epstein-Barr virus (EBV) receptor with the complement receptor type 2 (CR2) was established in three sets of experiments using the monoclonal antibodies, HB-5 and anti-B2, which recognize a Mr 145,000 B-lymphocyte membrane protein that is CR2. First, the rank order for binding of fluoresceinated EBV to four lymphoblastoid cell lines (SB, JY, Raji, and Molt-4) was identical to the rank order for binding of HB-5 and anti-B2 by analytical flow cytometry. Second, pretreatment of c...

  8. Programs Lucky and LuckyC - 3D parallel transport codes for the multi-group transport equation solution for XYZ geometry by Pm Sn method

    International Nuclear Information System (INIS)

    Powerful supercomputers are available today. MBC-1000M is one of Russian supercomputers that may be used by distant way access. Programs LUCKY and LUCKYC were created to work for multi-processors systems. These programs have algorithms created especially for these computers and used MPI (message passing interface) service for exchanges between processors. LUCKY may resolved shielding tasks by multigroup discreet ordinate method. LUCKYC may resolve critical tasks by same method. Only XYZ orthogonal geometry is available. Under little space steps to approximate discreet operator this geometry may be used as universal one to describe complex geometrical structures. Cross section libraries are used up to P8 approximation by Legendre polynomials for nuclear data in GIT format. Programming language is Fortran-90. 'Vector' processors may be used that lets get a time profit up to 30 times. But unfortunately MBC-1000M has not these processors. Nevertheless sufficient value for efficiency of parallel calculations was obtained under 'space' (LUCKY) and 'space and energy' (LUCKYC) paralleling. AUTOCAD program is used to control geometry after a treatment of input data. Programs have powerful geometry module, it is a beautiful tool to achieve any geometry. Output results may be processed by graphic programs on personal computer. (authors)

  9. Molecular Cloning and Characteristics of Sheep C3d Gene%绵羊C3d基因克隆及分子特征

    Institute of Scientific and Technical Information of China (English)

    岳耀敬; 焦硕; 郭宪; 冯瑞林

    2008-01-01

    从绵羊(Ovis aries)肝脏组织克隆到了补体C3d基因并对其核苷酸序列和推导的氨基酸序列以及蛋白结构进行了分析.绵羊补体C3d基因的编码区含有909个核苷酸,编码303个氨基酸残基(GenBank No.EF681138).绵羊C3d与人(Homo sapiens)、牛(Bos taurus)、山羊(Capra hircus)、野猪(Sus scrofa)、金仓鼠(Mesocricetus auratus)、小鼠(Mus musculus)、褐鼠(Rattus norvegicus)、大袋鼠(Macropus eugenii)、兔(Oryctolagus cuniculus)和原鸡(Gallus gallus)推导出的C3d氨基酸序列的一致性分别为80.4%,94.7%,96.9%,82.8%,81.1%,80.6%,80.2%,71.0%,75.2%和60.3%.绵羊与原鸡C3d的一致性最低为60.3%,而与其它动物C3d之间的一致性则较高为71.0%~96.9%.生物学软件分析发现,绵羊C3d蛋白有2个蛋白激酶C磷酸化位点,1个氨基葡聚糖附着位点,1个酪蛋白激酶Ⅱ磷酸化位点,1个酪氨酸激酶磷酸化位点,1个十四(烷)酰化位点.绵羊C3d二级结构中螺旋和转角交替出现,其中α螺旋占55.12%,β折叠为2.31%,转角区域为42.57%,这样的结构有利于其桶状结构的形成.ESyPred3D同源建模预测可知绵羊C3d三级结构与人C3d一样也形成由核心和外层构成的桶状分子结构.

  10. Characterization of the EBV/C3d receptor on the human Jurkat T cell line: evidence for a novel transcript.

    Science.gov (United States)

    Sinha, S K; Todd, S C; Hedrick, J A; Speiser, C L; Lambris, J D; Tsoukas, C D

    1993-06-15

    EBV is a human herpes virus that causes mononucleosis and is associated with various tumors. EBV infects cells via the CR2 that was previously thought to be expressed only on the surface of B cells and certain epithelial cells. Recent findings in our laboratory and those of others, however, have shown that the EBV receptor is also present on T cells. Our study shows that Jurkat human T cells have a molecule that reacts with both anti-CR2 antibodies and the third component of complement, C3. Furthermore, the data indicate that this molecule binds EBV detected by incubation with biotin-conjugated virus and streptavidin phycoerythrin. Viral binding is specific, as it is inhibited by nonconjugated virus, with anti-CR2 antibodies, and with an antibody reactive with the glycoprotein (gp350) that EBV uses to bind CR2. In addition, EBV variably infects Jurkat cells as demonstrated by the presence of transcripts of Epstein Barr nuclear Ag (EBNA-1) using the polymerase chain reaction. Immunoprecipitation experiments with anti-CR2 antibodies and SDS-PAGE analysis reveal a protein with an apparent molecular mass of 155 kDa which is higher than the one seen in B cells. The size of this molecule is reduced to 119 kDa upon endoglycosidase F treatment. Northern blot analysis of Jurkat poly(A)+ RNA shows a transcript of 4.7 kb upon probing with the B cell CR2 cDNA. This size is consistent with that of B cell CR2 mRNA. Two cDNA clones were identified upon screening of a Jurkat cell cDNA library with the B cell CR2 cDNA. One of the clones possesses an identical nucleotide sequence to the one corresponding to B cell CR2, whereas the other represents a differentially spliced transcript which lacks the exon 8b of B cell CR2. Analysis of Jurkat and Raji mRNA by PCR demonstrated the presence of this novel splice variant in both cell lines. PMID:8390533

  11. A complement receptor locus: genes encoding C3b/C4b receptor and C3d/Epstein-Barr virus receptor map to 1q32.

    Science.gov (United States)

    Weis, J H; Morton, C C; Bruns, G A; Weis, J J; Klickstein, L B; Wong, W W; Fearon, D T

    1987-01-01

    The alternative or classical pathways for complement system component C3 may be triggered by microorganisms and antigen-antibody complexes. In particular, an activated fragment of C3, C3b, covalently attaches to microorganisms or antigen-antibody complexes, which in turn bind to the C3b receptor, also known as complement receptor 1. The genes encoding the proteins that constitute the C3-activating enzymes have been cloned and mapped to a "complement activation" locus in the major histocompatibility complex, and we demonstrate in this study such a locus on the long arm of chromosome 1 at band 1q32. PMID:3782802

  12. Polyspecific drug and steroid clearance by an organic anion transporter of mammalian liver

    NARCIS (Netherlands)

    Bossuyt, [No Value; Muller, M; Hagenbuch, B; Meier, PJ

    1996-01-01

    An organic anion-transporting polypeptide that mediates sodium-independent uptake of negatively charged sulfobromophthalein and bile salts has recently been cloned from rat liver (Jacquemin et al., 1994). In this study we have extended the substrate specificity studies to neutral and positively char

  13. Identification of mono- or poly-specific monoclonal antibody to Porphyromonas gingivalis heat-shock protein 60

    OpenAIRE

    Choi, Jeomil; Lee, Sang-Yull; KIM, Koanhoi; Choi, Bong-Kyu; Kim, Myung-Jin

    2011-01-01

    Purpose The aim of this study was to define the immunoreactive specificity of Porphyromonas gingivalis (P. gingivalis) heat shock protein (HSP) 60 in periodontitis and atherosclerosis. Methods In an attempt to define the cross-reactive bacterial heat-shock protein with human self-antigen at molecular level, we have introduced a novel strategy for cloning hybridoma producing anti-P. gingivalis HSP 60 which is polyreactive to bacterial HSPs or to the human homolog. Results Five cross-reactive c...

  14. IL-1beta-induced pro-apoptotic signalling is facilitated by NCAM/FGF receptor signalling and inhibited by the C3d ligand in the INS-1E rat beta cell line

    DEFF Research Database (Denmark)

    Petersen, L G; Størling, J; Heding, P;

    2006-01-01

    AIMS/HYPOTHESIS: IL-1beta released from immune cells induces beta cell pro-apoptotic signalling via mitogen-activated protein kinases (MAPKs) and nuclear factor-kappaB (NF-kappaB). In neurons, the neural cell adhesion molecule (NCAM) signals to several elements involved in IL-1beta-induced pro......-apoptotic signalling in beta cells. Pancreatic beta cells express NCAM, but its biological effects in these cells are unclear. The aim of this study was to investigate whether there is cross-talk between NCAM signalling and cytokine-induced pro-apoptotic signalling. MATERIALS AND METHODS: Western blotting was used...... to investigate levels of NCAM and inducible nitric oxide synthase, phosphorylation of Src and MAPKs, and cleavage of caspase-3. MAPK activity was investigated with an in vitro kinase assay. Apoptosis was detected by cleaved caspase-3 and a Cell Death Detection ELISA(plus) assay. NCAM-induced fibroblast growth...

  15. A comparative study of venomics of Naja naja from India and Sri Lanka, clinical manifestations and antivenomics of an Indian polyspecific antivenom.

    Science.gov (United States)

    Sintiprungrat, Kitisak; Watcharatanyatip, Kamolwan; Senevirathne, W D S T; Chaisuriya, Papada; Chokchaichamnankit, Daranee; Srisomsap, Chantragan; Ratanabanangkoon, Kavi

    2016-01-30

    Naja naja (Indian cobra) from Sri Lanka and India is the WHO Category 1 medically important snakes in both countries. Some antivenom produced against Indian N. naja (NNi) were less effective against Sri Lankan N. naja (NNsl). Proteomes of NNi and NNsl venoms were studied by RP-HPLC, SDS-PAGE and LC/MS/MS. Six protein families were identified in both venoms with the most abundant were the 3 finger toxins (3FTs) where cytotoxins (CTX) subtype predominated, followed by phospholipase A2, cysteine-rich venom protein, snake venom metalloproteases, venom growth factors, and protease inhibitors. Qualitative and quantitative differences in the venomics profiles were observed. Some proteins were isolated from either NNi or NNsl venom. Postsynaptic neurotoxins (NTX) were identified for the first time in NNsl venom. Thus, there are geographic intra-specific variations of venom composition of the two N. naja. The relative abundance of CTX and NTX explained well the clinical manifestations of these venoms. Antivenomics study of an Indian antivenom (Vins) showed the antibodies effectively bound all venom toxins from both snakes but more avidly to the Indian venom proteins. The lower antibody affinity towards the 'heterologous' venom was the likely cause of poor efficacy of the Indian antivenom used to treat NNsl envenoming. PMID:26506536

  16. Antigens in human glioblastomas and meningiomas: Search for tumour and onco-foetal antigens. Estimation of S-100 and GFA protein

    DEFF Research Database (Denmark)

    Dittmann, L; Axelsen, N H; Norgaard-Pedersen, B;

    1977-01-01

    (glia specific); monospecific anti-GFA (glial fibrillary acidic protein), (astroglia specific); polyspecific anti-foetal brain (12-16th week of gestation); a polyspecific anti-glioblastoma antiserum, absorbed with insolubilized serum, haemolysate and normal brain extract; polyspecific anti...

  17. Alloimmunization and autoimmunization in transfusion dependent thalassemia major patients: Study on 319 patients

    Directory of Open Access Journals (Sweden)

    Hari Krishan Dhawan

    2014-01-01

    Full Text Available Background: The development of anti-red blood cell antibodies (both allo-and autoantibodies remains a major problem in thalassemia major patients. We studied the frequency of red blood cell (RBC alloimmunization and autoimmunization among thalassemia patients who received regular transfusions at our center and analyzed the factors, which may be responsible for development of these antibodies. Materials and Methods: The study was carried out on 319 multiply transfused patients with β-thalassemia major registered with thalassemia clinic at our institute. Clinical and transfusion records of all the patients were examined for age of patients, age at initiation of transfusion therapy, total number of blood units transfused, transfusion interval, status of splenectomy or other interventions. Alloantibody screening and identification was done using three cell and 11 cell panel (Diapanel, Bio-rad, Switzerland respectively. To detect autoantibodies, autocontrol was carried out using polyspecific coombs (IgG + C3d gel cards. Results: Eighteen patients out of total 319 patients (5.64% developed alloantibodies and 90 (28.2% developed autoantibodies. Nine out of 18 patients with alloantibodies also had autoantibodies. Age at first transfusion was significantly higher in alloimmunized than non-immunized patients (P = 0.042. Out of 23 alloantibodies, 52.17% belonged to Rh blood group system (Anti-E = 17%, Anti D = 13%, Anti-C = 13%, Anti-C w = 9%, 35% belonged to Kell blood group system, 9% of Kidd and 4% of Xg blood group system. Conclusion: Alloimmunization was detected in 5.64% of multitransfused thalassemia patients. Rh and Kell blood group system antibodies accounted for more than 80% of alloantibodies. This study re-emphasizes the need for RBC antigen typing before first transfusion and issue of antigen matched blood (at least for Rh and Kell antigen. Early institution of transfusion therapy after diagnosis is another means of decreasing

  18. Reduced hepatic uptake and intestinal excretion of organic cations in mice with a targeted disruption of the organic cation transporter 1 (Oct1 [Slc22a1]) gene

    NARCIS (Netherlands)

    Jonker, JW; Wagenaar, E; Mol, CAAM; Buitelaar, M; Koepsell, H; Smit, JW; Schinkel, AH

    2001-01-01

    The polyspecific organic cation transporter 1 (OCT1 [SLC22A1]) mediates facilitated transport of small (hydrophilic) organic cations. OCT1 is localized at the basolateral membrane of epithelial cells in the liver, kidney, and intestine and could therefore be involved in the elimination of endogenous

  19. Unveiling the nature of black mamba (Dendroaspis polylepis) venom through venomics and antivenom immunoprofiling: Identification of key toxin targets for antivenom development

    DEFF Research Database (Denmark)

    Laustsen, Andreas Hougaard; Lomonte, Bruno; Lohse, Brian;

    2015-01-01

    to toxicity by influencing the toxin biodistribution. ELISA immunoprofiling and preclinical assessment of neutralization showed that polyspecific antivenoms manufactured in South Africa and India were effective in the neutralization of D. polylepis venom, albeit showing different potencies. Antivenoms had...... by antivenoms....

  20. Live Transplantation in Children Antibody Production Against ِE. Coli Polypeptide (ECP) by ِDot Blotting and ELISA Methods for ECP Assay in Recombinant Drug and Patients Sera

    OpenAIRE

    A. Rabbani.; MH Sanati; Akrami, H.; G Ahangari

    2003-01-01

    Recombinant DNA technology made it possible to produce biological drugs and pharmaceutical companies produced recombinant human drugs. There have been reports on the formation of antibodies against residual host cell protein. For this reason, it is important to check the patients sera for antibodies which could possibly be induced by recombinant drug it self and/or by contaminating proteins of the host cell. The present report refers to the obtainment of polyspecific antisera directed against...

  1. Genetic processes and environmental significance of Lower Devonian brachiopod shell concentrations in Longmenshan area, Sichuan, China

    Science.gov (United States)

    Li, Fengjie; Qu, Xuelin; Du, Lingchun; Dai, Tingyong; Yang, Yuchuan; Li, Junwu; Yang, Chengjin

    2016-01-01

    The distinctive features of the Lower Devonian rocks of the Longmenshan area in southwestern China are brachiopod shell concentrations, especially in the Bailiuping, Ganxi and Xiejiawan Formations, where brachiopod shell concentrations occur widely throughout. Depending on the dominant skeletal elements, six types of shell concentrations can be distinguished: Protochonete, Acrospirifer, Howellella, Orientospirifer, polyspecific shell and polyspecific fragments concentrations. According to the shell features, taphonomic signature, host sediments and their relationships, four genetic models of the various shell concentrations are described in this paper. The genetic processes and distributions along an onshore-offshore area were clarified on the base of taphonomic analysis. Pavements of opportunistic species of Protochonetes are autochthonous assemblages living in quieter, deeper, more offshore waters near the maximum storm wave base. The pavements are the result of reduced sedimentation; the substrate was silty and water-saturated with variable turbidity soupy-mud. Transport by high-energy processes is interpreted as the final formation process of polyspecific fragments concentrations with most extensive scope from intertidal zone to the maximum storm wave base. The Acrospirifer, Howellella, and Orientospirifer concentrations have been stirred by storm wave action and quickly buried after short transport tempestite model. They are most easily preserved around the average storm wave-base. The polyspecific shell concentrations, which include large bivalves are autochthonous assemblages living in shallow and relatively quieter water near shore environments. Autochthonous assemblages of the opportunist Protochonetes bailiupingensis occurring in the Bailiuping Formation of the Longmenshan area not only record of storm events, but are also important features to identify and correlate the Bailiuping Formation in the field.

  2. A novel 95-kilodalton antigen of Wuchereria bancrofti infective larvae identified by species-specific monoclonal antibodies.

    OpenAIRE

    Burkot, T. R.; Kwan-Lim, G E; R. M. Maizels

    1996-01-01

    CBA and BALB/c mice produced polyspecific and monospecific polyclonal antibody responses, respectively, following immunization with Wuchereria bancrofti stage-3 larvae. Two monoclonal antibodies (MAbs) were produced from the immunized BALB/c mouse. These MAbs (both isotype M) recognized a previously undescribed highly expressed W. bancrofti antigen present in stage-3 larvae. The epitopes bound by the MAbs appear to be species specific for W. bancrofti since the MAbs did not bind to antigens o...

  3. Recombinant complement receptor 2 radiolabeled with [99mTc(CO3]+: a potential new radiopharmaceutical for imaging activated complement.

    Directory of Open Access Journals (Sweden)

    Adam Badar

    Full Text Available We describe the design and synthesis of a new Tc-99m labeled bioconjugate for imaging activated complement, based on Short Consensus Repeats 1 and 2 of Complement Receptor 2 (CR2, the binding domain for C3d. To avoid non specific modification of CR2 and the potential for modifying lysine residues critical to the CR2/C3d contact surface, we engineered a new protein, recombinant CR2 (rCR2, to include the C-terminal sequence VFPLECHHHHHH, a hexahistidine tag (for site-specific radiolabeling with [(99mTc(CO(3(OH(2(3](+. The protein was characterized by N-terminal sequencing, SDS-PAGE and size exclusion chromatography. To test the function of the recombinant CR2, binding to C3d was confirmed by enzyme-linked immunosorbent assay (ELISA. The function was further confirmed by binding of rCR2 to C3d(+ red blood cells (RBC which were generated by deposition of human or rat C3d and analyzed by fluorescence microscopy and flow cytometry. The affinity of rCR2 for C3d(+, in presence of 150 mM NaCl, was measured using surface plasma resonance giving rise to a K(D≈500 nM. Radiolabeling of rCR2 or an inactive mutant of rCR2 (K41E CR2 or an unrelated protein of a similar size (C2A with [(99mTc(CO(3(OH(2(3](+ at gave radiochemical yields >95%. Site-specifically radiolabeled rCR2 bound to C3d to C3d(+ RBC. Binding of radiolabeled rCR2 to C3d was inhibited by anti-C3d and the radiolabeled inactive mutant K41E CR2 and C2A did not bind to C3d(+ RBCs. We conclude that rCR2-Tc(99m has excellent radiolabeling, stability and C3d binding characteristics and warrants in vivo evaluation as an activated complement imaging agent.

  4. Immunoglobulin for necrotising soft tissue infections (INSTINCT)

    DEFF Research Database (Denmark)

    Madsen, Martin Bruun; Lange, Theis; Hjortrup, Peter Buhl;

    2016-01-01

    INTRODUCTION: Necrotising soft tissue infections (NSTI) are aggressive infections that can result in severe disability or death. Intravenous polyspecific immunoglobulin G (IVIG) is used as supplementary treatment for patients with NSTIs. The level of evidence is very low, but suggests that IVIG may....... Secondary outcomes are: mortality; time to resolution of shock; bleeding; sequential organ failure assessment scores on days 1-7; use of renal-replacement therapy, mechanical ventilation and vasopressors; days alive and out of hospital; amputation; and severe adverse reactions. CONCLUSION: This study...

  5. A COMPLEX OF INTERMEDIATE FILAMENT PROTEIN-DNA: A TARGET FOR AUTOANTIBODIES IN SYSTEMIC LUPUS ERYTHEMATOSUS?

    Institute of Scientific and Technical Information of China (English)

    阎锡德; S.Kuhn; P.Traub

    1995-01-01

    Autoantibodies in systemic lupus erythematosus which cross-react with double stranded DNA and in-termediate filament proteins are frequently reported.However,little is Known about the origin and the target of these antibodies.In this paper,a polyspecific monoclonal antibody,XY12,produced by the im-munization of genetically non-autoimmune mice with a DNA-protein complex is detsiled.Its antigen bind-ing patterms are very similar to the autoantibodies.The data suggest that these autoantibodies may be trig-gered by a circulating nucleoprotein.

  6. Resolution of the long-standing overprediction of the resonance to intercombination line-intensity ratio in mid-Z neonlike ions

    International Nuclear Information System (INIS)

    The Ne-like resonance 2p61S-2p53d 1P (3C) to intercombination 2p61S-2p53d 3D (3D) line-intensity ratio, R(3C/3D), has been extensively studied through high-accuracy measurements and calculations of atomic structure and collision cross sections. However, even state-of-the-art relativistic multiconfiguration atomic-physics codes generally predict values of R(3C/3D) that are significantly larger than those observed in coronal-density experiments. In this paper, predictions of R(3C/3D) across the Ne-like isoelectronic sequence from chromium to silver are brought into agreement with coronal-density experimental measurements in two steps: first by including a semiempirical correction in the collisional atomic data due to configuration-interaction effects, and next by including the effects of cascades on the upper level populations. The configuration-interaction correction is inspired by the observation that nearly all data-production codes fail to predict R(3C/3D) correctly and is justified theoretically by a careful analysis of configuration-interaction contributions to level energies. The dependence of R(3C/3D) with electron density and its agreement with moderate-density measurements are shown. A brief description of the application of our technique to line ratios in He- and Ni-like x-ray spectra is also given

  7. Deposition of C3, the terminal complement complex and vitronectin in primary biliary cirrhosis and primary sclerosing cholangitis

    DEFF Research Database (Denmark)

    Garred, P; Lyon, H; Christoffersen, P;

    1993-01-01

    -dependent cytotoxic mechanisms in the pathogenesis. Therefore, we investigated liver biopsy specimens from 21 patients with PBC, six patients with PSC and six controls for complement deposits by immunohistochemistry using polyclonal and monoclonal antibodies against C3d, the terminal complement complex (TCC......) and vitronectin (S-protein). We found C3d, TCC and vitronectin deposits only in the portal tracts. C3d and TCC were present in the walls of the hepatic arteries and in the connective tissue stroma but never around the bile ducts. We found vitronectin deposits throughout the connective tissue, often independent...... of the TCC deposits. When vitronectin and TCC were co-localized, the staining patterns were inverse; that is, intense staining for TCC accompanied weak staining for vitronectin and vice versa. Occasionally complete dissociation between TCC and vitronectin staining was observed. Deposits of TCC...

  8. Correlation of the activation of the fourth component of complement (C4) with disease activity in systemic lupus erythematosus.

    OpenAIRE

    Senaldi, G; Makinde, V A; Vergani, D; Isenberg, D. A.

    1988-01-01

    Levels of C4d, a fragment of C4 generated during activation of the classical complement pathway, were measured in the plasma of 48 patients with systemic lupus erythematosus, 11 with inactive (group 1), 23 with mildly active (group 2), 14 with moderately/severely active disease (group 3), and 30 healthy subjects. Levels of C3d, C4, and C3 were also measured and the C4d/C4 and C3d/C3 ratios calculated. C4d levels correlated with the degree of disease activity, being higher in group 3 than in g...

  9. Complement receptor type two (CR2,CR21): a target for influencing the humoral immune response and antigen-trapping.

    Science.gov (United States)

    Prodinger, W M

    1999-01-01

    Cellular receptors for complement C3 fragments deposited on antigens are important bricks in the wall defending against microbial pathogens. The part of complement receptor type 2 (CR2; CD21) deals with enhancing humoral immune responses and with long-term trapping of C3d-coated antigen by follicular dendritic cells. CR2 is also pivotal for Epstein-Barr virus (EBV) infection. Here, the current understanding, how CR2 interacts with its ligands C3d, EBV, and CD23 is summarized. The potential to target CR2 for clinical therapy or immunization purposes are discussed. PMID:10741859

  10. Identification of murine complement receptor type 2.

    OpenAIRE

    Fingeroth, J D; Benedict, M A; Levy, D.N.; Strominger, J L

    1989-01-01

    A rabbit antiserum reactive with the human complement component C3d/Epstein-Barr virus receptor (complement receptor type 2, CR2) immunoprecipitates a Mr 155,000 murine B-cell surface antigen. The apparent molecular weight and cellular distribution of this murine antigen are similar to those of human CR2. Cells expressing the murine protein bind sheep erythrocytes coated with antibody and murine C1-C3d but do not bind Epstein-Barr virus at all. The monospecific antiserum to human CR2 together...

  11. Monoclonal antibodies against complement 3 neoantigens for detection of immune complexes and complement activation. Relationship between immune complex levels, state of C3, and numbers of receptors for C3b.

    OpenAIRE

    Aguado, M. T.; LAMBRIS, J. D.; Tsokos, G C; de Burger, R; Bitter-Suermann, D.; Tamerius, J D; Dixon, F J; Theofilopoulos, A N

    1985-01-01

    C3-bearing immune complexes and C3 activation products were detected by using two monoclonal antibodies, one specific for a neoantigenic determinant on C3c and the other for C3d. To quantitate immune complexes, the anti-C3c or anti-C3d antibodies were fixed to microtiter plates and reacted with test plasma. The binding of C3-bearing immune complexes in this plasma was then measured with radioisotope- or enzyme-labeled anti-human IgG. To test for C3 breakdown products, solid-phase monoclonal a...

  12. In situ expansion of T cells that recognize distinct self-antigens sustains autoimmunity in the CNS.

    Science.gov (United States)

    Ramadan, Abdulraouf; Lucca, Liliana E; Carrié, Nadège; Desbois, Sabine; Axisa, Pierre-Paul; Hayder, Myriam; Bauer, Jan; Liblau, Roland S; Mars, Lennart T

    2016-05-01

    Polyspecific T cells recognizing multiple distinct self-antigens have been identified in multiple sclerosis and other organ-specific autoimmune diseases, but their pathophysiological relevance remains undetermined. Using a mouse model of multiple sclerosis, we show that autoimmune encephalomyelitis induction is strictly dependent on reactivation of pathogenic T cells by a peptide (35-55) derived from myelin oligodendrocyte glycoprotein (MOG). This disease-inducing response wanes after onset. Strikingly, the progression of disease is driven by the in situ activation and expansion of a minority of MOG35-55-specific T cells that also recognize neurofilament-medium (NF-M)15-35, an intermediate filament protein expressed in neurons. This mobilization of bispecific T cells is critical for disease progression as adoptive transfer of NF-M15-35/MOG35-55 bispecific T cell lines caused full-blown disease in wild-type but not NF-M-deficient recipients. Moreover, specific tolerance through injection of NF-M15-35 peptide at the peak of disease halted experimental autoimmune encephalomyelitis progression. Our findings highlight the importance of polyspecific autoreactive T cells in the aggravation and perpetuation of central nervous system autoimmunity. PMID:27000832

  13. Design of Protein Multi-specificity Using an Independent Sequence Search Reduces the Barrier to Low Energy Sequences.

    Directory of Open Access Journals (Sweden)

    Alexander M Sevy

    2015-07-01

    Full Text Available Computational protein design has found great success in engineering proteins for thermodynamic stability, binding specificity, or enzymatic activity in a 'single state' design (SSD paradigm. Multi-specificity design (MSD, on the other hand, involves considering the stability of multiple protein states simultaneously. We have developed a novel MSD algorithm, which we refer to as REstrained CONvergence in multi-specificity design (RECON. The algorithm allows each state to adopt its own sequence throughout the design process rather than enforcing a single sequence on all states. Convergence to a single sequence is encouraged through an incrementally increasing convergence restraint for corresponding positions. Compared to MSD algorithms that enforce (constrain an identical sequence on all states the energy landscape is simplified, which accelerates the search drastically. As a result, RECON can readily be used in simulations with a flexible protein backbone. We have benchmarked RECON on two design tasks. First, we designed antibodies derived from a common germline gene against their diverse targets to assess recovery of the germline, polyspecific sequence. Second, we design "promiscuous", polyspecific proteins against all binding partners and measure recovery of the native sequence. We show that RECON is able to efficiently recover native-like, biologically relevant sequences in this diverse set of protein complexes.

  14. Solution Binding and Structural Analyses Reveal Potential Multidrug Resistance Functions for SAV2435 and CTR107 and Other GyrI-like Proteins.

    Science.gov (United States)

    Moreno, Andrew; Froehlig, John R; Bachas, Sharrol; Gunio, Drew; Alexander, Teressa; Vanya, Aaron; Wade, Herschel

    2016-08-30

    Multidrug resistance (MDR) refers to the acquired ability of cells to tolerate a broad range of toxic compounds. One mechanism cells employ is to increase the level of expression of efflux pumps for the expulsion of xenobiotics. A key feature uniting efflux-related mechanisms is multidrug (MD) recognition, either by efflux pumps themselves or by their transcriptional regulators. However, models describing MD binding by MDR effectors are incomplete, underscoring the importance of studies focused on the recognition elements and key motifs that dictate polyspecific binding. One such motif is the GyrI-like domain, which is found in several MDR proteins and is postulated to have been adapted for small-molecule binding and signaling. Here we report the solution binding properties and crystal structures of two proteins containing GyrI-like domains, SAV2435 and CTR107, bound to various ligands. Furthermore, we provide a comparison with deposited crystal structures of GyrI-like proteins, revealing key features of GyrI-like domains that not only support polyspecific binding but also are conserved among GyrI-like domains. Together, our studies suggest that GyrI-like domains perform evolutionarily conserved functions connected to multidrug binding and highlight the utility of these types of studies for elucidating mechanisms of MDR. PMID:27505298

  15. The conserved structure of snake venom toxins confers extensive immunological cross-reactivity to toxin-specific antibody.

    Science.gov (United States)

    Harrison, R A; Wüster, W; Theakston, R D G

    2003-03-01

    We have demonstrated previously that antisera from mice immunised with DNA encoding the carboxy-terminal domain (JD9) of a potent haemorrhagic metalloproteinase, jararhagin, neutralised over 70% of the haemorrhagic activity of the whole Bothrops jararaca venom. Here, we demonstrate that the JD9-specific antibody possesses extensive immunological reactivity to venom components in snakes of distinct species and genera. The polyspecific immunological reactivity of the antibody showed a correlation with amino acid sequence identity and with predicted antigenic domains of JD9-analogues in venoms of snakes with closest phylogenetic links to B. jararaca. This study further promotes the potential of DNA immunisation to generate toxin-specific antibodies with polyspecific cover. An analysis of the reactivity of the JD9-specific antisera to B. atrox complex venoms that exhibited intraspecific variation in the venom proteome revealed, however, that the toxin-specific approach to antivenom development requires a more in-depth knowledge of the target molecules than is required for conventional antivenoms. PMID:12657313

  16. Interactions of opsonized immune complexes with whole blood cells: binding to erythrocytes restricts complex uptake by leucocyte populations

    DEFF Research Database (Denmark)

    Nielsen, C H; Svehag, S E; Marquart, H V;

    1994-01-01

    binding, the main contributors being B cells. E initially inhibited and then later enhanced the IC binding to lymphocytes, suggesting that E promote B cell uptake of C3d,g-covered IC via CR2. Our findings, that E can restrict the IC uptake by circulating leucocytes, and that an IC-induced degranulation...

  17. Human immune response to pneumococcal polysaccharides : Complement-mediated localization preferentially on CD21-positive splenic marginal zone B cells and follicular dendritic cells

    NARCIS (Netherlands)

    Peset Llopis, MJ; Harms, Geert; Hardonk, MJ; Timens, W

    1996-01-01

    A functionally intact spleen with a marginal zone, containing B cells with high density of surface C3d-receptors (CD21), is essential for the ability to induce a primary immune response to thymus-independent type 2 (TI-2) antigens. Main representatives of natural TI-2 antigens are capsular pneumococ

  18. Utilization of stable isotopes for studying biological macromolecules by high-resolution NMR; Utilisation des isotopes stables pour l`etude de macromolecules biologiques par R.M.N. a haute resolution

    Energy Technology Data Exchange (ETDEWEB)

    Jamin, N.; Gilles, N.; Lirsac, P.N.; Menez, A.; Toma, F. [CEA Centre d`Etudes de Saclay, 91 - Gif-sur-Yvette (France). Direction des Sciences du Vivant; Bostadt, A.; Gabrielsen, O.S. [Oslo Univ. (Norway)

    1994-12-31

    Stable isotope labelling applications for nuclear magnetic resonance study of proteins are reviewed and several examples of utilization of these techniques are given. Resolution limitations for very large protein are discussed. Examples are also given for labelling other biomolecules such as ARN and ADN with {sup 2}H, {sup 15}N and {sup 13}C (3D structure of proteins). 2 figs., 39 refs.

  19. Vibrational Spectroscopy of CH/CD Stretches in Propadiene: An Algebraic Approach

    Institute of Scientific and Technical Information of China (English)

    Joydeep Choudhury; Nirmal Kumar Sarkar; Srinivasa Rao Kaxumuri; Ramendu Bhattacharjee

    2009-01-01

    Using Hamiltonian based on Lie algebraic method, the stretching vibrational modes of C3H4 and C3D4 molecules are calculated up to higher overtones. The model appears to describe C-H and C-D stretching modes with less number of parameters. The locality parameter ξ confirms the highly local behaviour of the stretching modes of these molecules.

  20. Comparison of Isocentric C-Arm 3-Dimensional Navigation and Conventional Fluoroscopy for Percutaneous Retrograde Screwing for Anterior Column Fracture of Acetabulum: An Observational Study.

    Science.gov (United States)

    He, Jiliang; Tan, Guoqing; Zhou, Dongsheng; Sun, Liang; Li, Qinghu; Yang, Yongliang; Liu, Ping

    2016-01-01

    Percutaneous screw insertion for minimally displaced or reducible acetabular fracture using x-ray fluoroscopy and computer-assisted navigation system has been advocated by some authors. The purpose of this study was to compare intraoperative conditions and clinical results between isocentric C-arm 3-dimensional (Iso-C 3D) fluoroscopy and conventional fluoroscopy for percutaneous retrograde screwing of acetabular anterior column fracture.A prospective cohort study was conducted. A total of 22 patients were assigned to 2 different groups: 10 patients in the Iso-C 3D navigation group and 12 patients in the conventional group. The operative time, fluoroscopic time, time of screw insertion, blood loss, and accuracy were analyzed between the 2 groups.There were significant differences in operative time, screw insertion time, fluoroscopy time, and mean blood loss between the 2 groups. Totally 2 of 12 (16.7%) screws were misplaced in the conventional fluoroscopy group, and all 10 screws were in safe zones in the navigation group. Percutaneous screw fixation using the Iso-C 3D computer-assisted navigation system significantly reduced the intraoperative fluoroscopy time and blood loss in percutaneous screwing for acetabular anterior column fracture.The Iso-C 3D computer-assisted navigation system provided a reliable and effective method for percutaneous screw insertion in acetabular anterior column fractures compared to conventional fluoroscopy.

  1. Domain Modeling: NP_003794.3 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_003794.3 chr18 Crystal structure of a prolactin receptor antagonist bound to the... extracellular domain of the prolactin receptor c3d48r_ chr18/NP_003794.3/NP_003794.3_holo_933-1136.pdb psi-blast 0 ...

  2. Infants and children with cow milk allergy/intolerance. Investigation of the uptake of cow milk protein and activation of the complement system

    DEFF Research Database (Denmark)

    Husby, S; Høst, A; Teisner, B;

    1990-01-01

    exclusion chromatography indicated immunoreactive material as small aggregates. Plasma samples were analysed by electroimmunoassay for complement factor split product C3d, which was not demonstrable above background values in any of the cases. CMAI in infants and children may not be related to systemic...

  3. Hyperpolarized (13) C,(15) N2 -Urea MRI for assessment of the urea gradient in the porcine kidney

    DEFF Research Database (Denmark)

    Hansen, Esben S S; Stewart, Neil J; Wild, Jim M;

    2016-01-01

    function in healthy porcine kidneys resembling the human physiology. METHODS: Five healthy female Danish domestic pigs (weight 30 kg) were scanned at 3 Tesla (T) using a (13) C 3D balanced steady-state MR pulse sequence following injection of hyperpolarized (13) C,(15) N2 -urea via a femoral vein catheter...

  4. Immune haemolytic anaemia associated with ampicillin dependent warm antibodies and high titre cold agglutinins in a patient with Mycoplasma pneumonia

    DEFF Research Database (Denmark)

    Mickley, H; Sørensen, P G

    1984-01-01

    A case of severe immune haemolytic anaemia in a 54-year-old man suffering from Mycoplasma pneumonia is presented. A strongly positive direct Coombs test with erythrocyte bound IgG, C3d and C4 was demonstrated during the haemolytic process. Further, serologic investigations revealed ampicillin...

  5. 三维编织炭纤维增强环氧树脂复合材料的吸湿特性%Moisture Absorption Characteristics of 3D Braided Carbon Fiber Reinforced Epoxy Resin Composites

    Institute of Scientific and Technical Information of China (English)

    王玉果

    2009-01-01

    Three-dimensionally(_3D)braided carbon fiber reinforced epoxy resin(C_3D/EP)composites have been prepared by resin transfer molding(RTM)process. The moisture absorption characteristics,influence of temperature on the water uptake,and changes in the flexural strength during water absorption of C_3D/EP composites have been studied in the water absorption experiment. Experiment results show that the equilibrium moisture content of the C_3D/EP composites is lower than that of unreinforced epoxy resin but slightly higher than that of the long carbon fiber reinforced epoxy resin(C_L/EP)composites. The absorption behavior at the initial stage conforms to Fick's law of diffusion while the whole absorption behavior of epoxy resin composites can be described with the Sigmoidal model. The flexural strength of the C_3D/EP composites decreases quickly with immersion time at the early stage and then levels off,which is in agreement with the absorption content-time curve. It is also found that temperature affects the absorption process greatly. The absorption rate and equilibrium moisture content of the C_3D/EP composites increase with the rise of temperature. The higher the tempera-ture,more remarkable the loss of flexural strength. It is thus concluded that the reduction of mechanical property is related to the water absorption content of the C_3D/EP composites.%为了研究三维编织复合材料的吸湿行为,利用树脂传递模塑(RTM)工艺制备了三维编织炭纤维增强环氧树脂(C3D/EP)复合材料.通过吸水实验,研究了该材料的吸湿规律、温度对吸湿的影响以及吸湿过程中复合材料力学性能的变化.结果表明:C_(3D)/EP复合材料吸湿初期符合Fick扩散定律,但整个吸湿行为可用Sigmoidal曲线来描述;温度可加速C_(3D)EP复合材料的吸湿速率,并使平衡吸湿量提高;在吸湿过程中,C_(3D)EP复合材料的弯曲强度随吸湿时间的延长而下降.先快后慢,与吸湿曲线相对应,而且温

  6. The Structure-Function Relationships of Complement Receptor Type 2 (CR2; CD21).

    Science.gov (United States)

    Hannan, Jonathan Paul

    2016-01-01

    Human complement receptor type 2 (CR2; CD21) is a surface-associated glycoprotein which binds to a variety of endogenous ligands, including the complement component C3 fragments iC3b, C3dg and C3d, the low-affinity IgE receptor CD23, and the type I cytokine, interferon-alpha. CR2 links the innate complement-mediated immune response to pathogens and foreign antigens with the adaptive immune response by binding to C3d that is covalently attached to targets, and which results in a cell signalling phenomenon that lowers the threshold for B cell activation. Variations or deletions of the CR2 gene in humans, or the Cr2 gene in mice associate with a variety of autoimmune and inflammatory conditions. A number of infectious agents including Epstein-Barr virus (EBV), Human Immunodeficiency Virus (HIV) and prions also bind to CR2 either directly or indirectly by means of C3d-targeted immune complexes. In this review we discuss the interactions that CR2 undertakes with its best characterized ligands C3d, CD23 and the EBV gp350/220 envelope protein. To date only a single physiologically relevant complex of CR2 with one of its ligands, C3d, has been elucidated. By contrast, the interactions with CD23 and EBV gp350/220, while being important from physiologic and disease-associated standpoints, respectively, are only incompletely understood. A detailed knowledge of the structure-function relationships that CR2 undergoes with its ligands is necessary to understand the implications of using recombinant CR2 in therapeutic or imaging agents, or alternatively targeting CR2 to down-regulate the antibody mediated immune response in cases of autoimmunity. PMID:26916158

  7. The Effect of Bovine IFN-α on the Immune Response in Guinea Pigs Vaccinated with DNA Vaccine of Foot-and-Mouth Disease Virus

    Institute of Scientific and Technical Information of China (English)

    Hui-Chen GUO; Zai-Xin LIU; Shi-Qi SUN; Qing-Wen LENG; Dong LI; Xiang-Tao LIU; Qing-Ge XIE

    2004-01-01

    In this study, we constructed recombinant plasmid pcDNA3.1/P 12X3C3D including P 1, 2A,3C, 3D and part of 2B gene of FMDV and pcDNA3.1/IFN containing the gene encoding bovine IFN-α. We inoculated the DNA vaccine pcDNA3.1/P 12X3C3D with or without pcDNA3.1/IFN to evaluate the efficiency of this DNA vaccine and the immunogenicity of DNA vaccine enhanced by the co-delivery with pcDNA3.1/IFN. After two times of vaccination with DNA vaccine, all of guinea pigs were challenged with 103 ID50 FMDV type O. Anti-FMDV antibody levels were detected by ELISA and T lymphocyte proliferation response was tested by MTT assay. The result shows that guinea pigs inoculated by pcDNA3. 1/P 12X3C3D alone or with pcDNA3.1/IFN generated specific antibodies and induced an FMDV-specific T lymphocyte proliferation response. FMDV challenge tests showed that one in four guinea pigs immunized by pcDNA3.1/P 12X3C3D with pcDNA3.1/IFN was protected from the FMDV serotype O infection. This result indicated that the efficiency of the DNA vaccine was enhanced by co-delivery with pcDNA3.1/IFN. However, the protection rate was considerably lower than that immunized with conventional FMD vaccine.

  8. The Structure-Function Relationships of Complement Receptor Type 2 (CR2; CD21).

    Science.gov (United States)

    Hannan, Jonathan Paul

    2016-01-01

    Human complement receptor type 2 (CR2; CD21) is a surface-associated glycoprotein which binds to a variety of endogenous ligands, including the complement component C3 fragments iC3b, C3dg and C3d, the low-affinity IgE receptor CD23, and the type I cytokine, interferon-alpha. CR2 links the innate complement-mediated immune response to pathogens and foreign antigens with the adaptive immune response by binding to C3d that is covalently attached to targets, and which results in a cell signalling phenomenon that lowers the threshold for B cell activation. Variations or deletions of the CR2 gene in humans, or the Cr2 gene in mice associate with a variety of autoimmune and inflammatory conditions. A number of infectious agents including Epstein-Barr virus (EBV), Human Immunodeficiency Virus (HIV) and prions also bind to CR2 either directly or indirectly by means of C3d-targeted immune complexes. In this review we discuss the interactions that CR2 undertakes with its best characterized ligands C3d, CD23 and the EBV gp350/220 envelope protein. To date only a single physiologically relevant complex of CR2 with one of its ligands, C3d, has been elucidated. By contrast, the interactions with CD23 and EBV gp350/220, while being important from physiologic and disease-associated standpoints, respectively, are only incompletely understood. A detailed knowledge of the structure-function relationships that CR2 undergoes with its ligands is necessary to understand the implications of using recombinant CR2 in therapeutic or imaging agents, or alternatively targeting CR2 to down-regulate the antibody mediated immune response in cases of autoimmunity.

  9. Highly sensitive detection of the group A Rotavirus using Apolipoprotein H-coated ELISA plates compared to quantitative real-time PCR

    Directory of Open Access Journals (Sweden)

    Veas Francisco

    2011-02-01

    Full Text Available Abstract Background The principle of a capture ELISA is binding of specific capture antibodies (polyclonal or monoclonal to the surface of a suitable 96 well plate. These immobilized antibodies are capable of specifically binding a virus present in a clinical sample. Subsequently, the captured virus is detected using a specific detection antibody. The drawback of this method is that a capture ELISA can only function for a single virus captured by the primary antibody. Human Apolipoprotein H (ApoH or β2-glycoprotein 1 is able to poly-specifically bind viral pathogens. Replacing specific capture antibodies by ApoH should allow poly-specific capture of different viruses that subsequently could be revealed using specific detection antibodies. Thus, using a single capture ELISA format different viruses could be analysed depending on the detection antibody that is applied. In order to demonstrate that this is a valid approach we show detection of group A rotaviruses from stool samples as a proof of principle for a new method of capture ELISA that should also be applicable to other viruses. Results Stool samples of different circulating common human and potentially zoonotic group A rotavirus strains, which were pretested in commercial EIAs and genotyped by PCR, were tested in parallel in an ApoH-ELISA set-up and by quantitative real-time PCR (qPCR. Several control samples were included in the analysis. The ApoH-ELISA was suitable for the capture of rotavirus-particles and the detection down to 1,000 infectious units (TCID50/ml. Subsets of diagnostic samples of different G- and P-types were tested positive in the ApoH-ELISA in different dilutions. Compared to the qPCR results, the analysis showed high sensitivity, specificity and low cross-reactivity for the ApoH-ELISA, which was confirmed in receiver operating characteristics (ROC analysis. Conclusions In this study the development of a highly sensitive and specific capture ELISA was demonstrated by

  10. Analysis of camelid antibodies for antivenom development: Neutralisation of venom-induced pathology.

    Science.gov (United States)

    Cook, Darren A N; Owen, Timothy; Wagstaff, Simon C; Kinne, Joerg; Wernery, Ulrich; Harrison, Robert A

    2010-09-01

    Camelid IgG has been reported to be less immunogenic, less able to activate the complement cascade and more thermostable than IgG from other mammals, and has the ability to bind antigens that are unreactive with other mammalian IgGs. We are investigating whether these attributes of camelid IgG translate into antivenom with immunological and venom-neutralising efficacy advantages over conventional equine and ovine antivenoms. The objective of this study was to determine the preclinical venom-neutralising effectiveness of IgG from camels immunised with venoms, individually or in combination, of the saw-scaled viper, Echis ocellatus, the puff adder, Bitis arietans and the spitting cobra, Naja nigricollis - the most medically-important snake species in West Africa. Neutralisation of the pathological effects of venoms from E. ocellatus, B. arietans and N. nigricollis by IgG from the venom-immunised camels, or commercial antivenom, was compared using assays of venom lethality (ED(50)), haemorrhage (MHD) and coagulopathy (MCD). The E. ocellatus venom ED(50), MHD and MCD results of the E. ocellatus monospecific camel IgG antivenom were broadly equivalent to comparable ovine (EchiTAbG, MicroPharm Ltd, Wales) and equine (SAIMR Echis, South African Vaccine Producer, South Africa) antivenoms, although the equine antivenom required half the amount of IgG. The B. arietans monospecific camel IgG neutralised the lethal effects of B. arietans venom at one fourth the concentration of the SAIMR polyspecific antivenom (a monospecific B. arietans antivenom is not available). The N. nigricollis camel IgG antivenom was ineffective (at the maximum permitted dose, 100 mul) against the lethal effects of N. nigricollis venom. All the equine polyspecific antivenoms required more than 100 microl to be effective against this venom. The polyspecific camel IgG antivenom, prepared from five camels, was effective against the venom-induced effects of E. ocellatus but not against that of B. arietans

  11. Knowledge-base for interpretation of cerebrospinal fluid data patterns. Essentials in neurology and psychiatry.

    Science.gov (United States)

    Reiber, Hansotto

    2016-06-01

    The physiological and biophysical knowledge base for interpretations of cerebrospinal fluid (CSF) data and reference ranges are essential for the clinical pathologist and neurochemist. With the popular description of the CSF flow dependent barrier function, the dynamics and concentration gradients of blood-derived, brain-derived and leptomeningeal proteins in CSF or the specificity-independent functions of B-lymphocytes in brain also the neurologist, psychiatrist, neurosurgeon as well as the neuropharmacologist may find essentials for diagnosis, research or development of therapies. This review may help to replace the outdated ideas like "leakage" models of the barriers, linear immunoglobulin Index Interpretations or CSF electrophoresis. Calculations, Interpretations and analytical pitfalls are described for albumin quotients, quantitation of immunoglobulin synthesis in Reibergrams, oligoclonal IgG, IgM analysis, the polyspecific ( MRZ- ) antibody reaction, the statistical treatment of CSF data and general quality assessment in the CSF laboratory. The diagnostic relevance is documented in an accompaning review. PMID:27332077

  12. Characterisation of non-maternal serum proteins in amniotic fluid at weeks 16 to 18 of gestation

    DEFF Research Database (Denmark)

    Drøhse, H; Christensen, H; Myrhøj, Vibeke;

    1998-01-01

    Proteins found in amniotic fluid are mainly serum proteins, probably of maternal origin. About 5% of the total protein concentration has the potential of being fetal or decidual in origin. Only a few of these proteins have been isolated and characterised. In order to describe the foetal...... and decidual components in amniotic fluid more extensively, a polyspecific antiserum to amniotic fluid at weeks 16-18 of gestation was raised. Specificities in the antiserum to serum proteins were removed by adsorption. Several proteins of non-serum protein origin reacted with the antiserum. Three...... of these proteins were chosen for isolation and further characterisation. With the use of immunological methods, SDS-PAGE and N-terminal sequencing we identified two of the proteins as C-terminal propeptides of procollagen Type I and Type III, which have not hitherto been described in amniotic fluid. The third...

  13. Vocal correlates of individual sooty mangabey travel speed and direction.

    Science.gov (United States)

    Neumann, Christof; Zuberbühler, Klaus

    2016-01-01

    Many group-living animals coordinate movements with acoustic signals, but so far most studies have focused on how group movements are initiated. In this study, we investigated movement patterns of wild sooty mangabeys (Cercocebus atys), a mostly terrestrial, forest-dwelling primate. We provide quantitative results showing that vocalization rates of mangabey subgroups, but not of focal individuals, correlated with focal individuals' current movement patterns. More interestingly, vocal behaviour predicted whether individuals changed future speed, and possibly future travel direction. The role of vocalizations as a potential mechanism for the regulation of group movement was further highlighted by interaction effects that include subgroup size and the quality of poly-specific associations. Collectively, our results suggest that primate vocal behaviour can function beyond travel initiation in coordination and regulation of group movements. PMID:27547587

  14. Discovering sequence motifs in quantitative and qualitative pepetide data

    DEFF Research Database (Denmark)

    Andreatta, Massimo

    and interpret such data. The first paper in this thesis presents a new, publicly available method based on artificial neural networks that allows custom analysis of quantitative peptide data. The online NNAlign web-server provides a simple yet powerful tool for the discovery of sequence motifs in large...... of interactions in a single experiment, with virtually unlimited choice of potential targets and variants of these targets. However, the amount and complexity of data produced by high-throughput techniques poses serious challenges to researchers of limited bioinformatics expertise who need to analyze...... with the presence of multiple motifs, due to the experimental setup or the actual poly-specificity of the receptor, in peptide data. A new algorithm, based on Gibbs sampling, identifies multiple specificities by performing two tasks simultaneously: alignment and clustering of peptide data. The method, available...

  15. Cloning and expression of the Legionella micdadei "common antigen" in Escherichia coli

    DEFF Research Database (Denmark)

    Bangsborg, Jette Marie; Collins, M T; Høiby, N;

    1989-01-01

    To study individual Legionella antigens, a Legionella micdadei genomic library in Escherichia coli SC181 was established. Partially Sau3A digested L. micdadei DNA fragments (15-25 kilobase pairs (kb] were cloned into the tetracycline resistance gene of the cosmid vector pHC79. Four thousand...... ampicillin resistant recombinants were obtained; seven hundred were screened for expression of Legionella antigens in Western blot analysis with a polyspecific E. coli-absorbed anti-L. micdadei rabbit antibody. One of the positive clones expressed a 60 kilodalton (K) antigen, which reacted strongly...... will provide important information with respect to genetic vs. antigenic relatedness among Legionellae and other Gram-negative species, as well as to CA structure and possible function....

  16. Development of venom toxin-specific antibodies by DNA immunisation: rationale and strategies to improve therapy of viper envenoming.

    Science.gov (United States)

    Harrison, R A

    2004-04-16

    DNA vaccination induces potent cellular immune responses against infectious and parasitic intracellular pathogens. This paper illustrates that DNA immunisation protocols can be adapted to induce high titre antibody responses with potential to improve the treatment of systemic snake envenoming that kills 20000 people annually in Africa. Envenoming by the saw-scaled vipers and puff adders are responsible for the majority of these deaths. DNA sequences encoding haemorrhagic, pro- and anti-coagulant and other haemostasis-disruptive venom toxins from these vipers showed extensive cross-specific and cross-generic sequence and structural similarities. The predicted antigenic profiles of these toxin sequences are utilised to design DNA immunisation constructs to generate toxin-specific antibodies with potential to polyspecifically neutralise venoms from the most medically-important African vipers. PMID:15068847

  17. Haemostatic dysfunction and acute renal failure following envenoming by Merrem's hump-nosed viper (Hypnale hypnale) in Sri Lanka: first authenticated case.

    Science.gov (United States)

    de Silva, A; Wijekoon, A S; Jayasena, L; Abeysekera, C K; Bao, C X; Hutton, R A; Warrell, D A

    1994-01-01

    A five years old boy was bitten by a Merrem's hump-nosed viper (Hypnale hypnale) in Central Province, Sri Lanka. He developed local swelling, incoagulable blood, thrombocytopenia, bleeding into the gastrointestinal tract, and acute renal failure. Treatment with Serum Institute of Indian polyspecific antivenom (specific for venoms of cobra, common krait, Russell's viper and saw-scaled viper) had no effect on the coagulopathy, which persisted for more than a week. The boy recovered after 27 d in hospital, during which he was treated with peritoneal dialysis for renal failure. Laboratory studies demonstrated that the venom of H. hypnale was procoagulant, fibrinolytic and aggregated platelets. This first authenticated case of life-threatening acute renal failure and haemostatic disturbances caused by H. hypnale, a species responsible for 27% of snake bites in Sri Lanka, demonstrates the need for a new antivenom with specific activity against the venom of this species. PMID:8036678

  18. Rheumatoid factors, B cells and immunoglobulin genes.

    Science.gov (United States)

    Jefferis, R

    1995-04-01

    The paradigm of self, non-self discrimination in the immune system is under review as autoreactive B or T cells are increasingly delineated within normal individuals. The products of autoreactive B cells are, mostly, polyspecific IgM antibodies of low affinity. These 'natural' antibodies include rheumatoid factors (RF) encoded by unmutated germline immunoglobulin genes. In rheumatoid arthritis (RA) the RF may be of the IgM, IgG or IgA isotype, show evidence of somatic mutation and have increased affinity; consistent with maturation of an antigen driven immune response. This response could be initiated or driven by an auto-immunogenic form of IgG or an exogenous cross-reactive antigen. Changes in galactosylation of IgG have been reported to be a valuable diagnostic and prognostic indicator in RA. Speculation that these changes may precipitate some of the disease processes is critically reviewed.

  19. The value of csf analysis for the differential diagnosis of HTLV-I associated myelopathy and multiple sclerosis Valor da análise do LCR para o diagnóstico diferencial de mielopatia associada ao HTLV-I e esclerose múltipla

    Directory of Open Access Journals (Sweden)

    Marzia Puccioni-Sohler

    1995-12-01

    Full Text Available Cerebrospinal fluid (CSF and serum of 17 patients with HAM/TSP (HTLV-I associated myelopathy/ tropical spastic paraparesis, six with multiple sclerosis and six with idiopathic epilepsy (non inflammatory control from Brazil were analysed for the presence of intrathecal synthesis of virus-specific antibodies against measles, rubella, varicella zoster virus and herpes simplex virus by enzyme-linked immunosorbent assay (ELISA. All HAM/TSP and multiple sclerosis cases had an intrathecal immune response (oligoclonal IgG. In HAM/TSP, only 1/17 case showed a polyspecific intrathecal immune response against measles and rubella virus. In multiple sclerosis, specific antibodies against measles and rubella (MRZ response were observed in all patients but not in the control with idiopathic epilepsy. The diagnostic and theoretical relevance of mono- and polyspecific immune responses is discussed for these chronic neurological diseases.Amostras de líquido cefalorraquidiano (LCR e soro de 17 pacientes brasileiros com HAM/TSP, seis com esclerose múltipla e seis com epilepsia idiopática (controle não-inflamatório foram analisadas para a presença de anticorpos para os vírus do sarampo, rubéola, varicela zoster e herpes simples pelo método de ELISA. Todos os casos de HAM/TSP e esclerose múltipla tinham resposta imune intratecal (IgG oligoclonal. Somente 1/17 casos de HAM/TSP apresentavam resposta imune poliespecifica intratecal para sarampo e rubéola. Anticorpos específicos para sarampo e rubeola (resposta MRZ foram observados em todos os pacientes com esclerose múltipla, mas não nos controles com epilepsia idiopática. A relevância das respostas poliespecifica e monoespecifica é discutida para essas doenças neurológicas crônicas.

  20. Measles IgG antibody index correlates with T2 lesion load on MRI in patients with early multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Berit Rosche

    Full Text Available BACKGROUND: B cells and humoral immune responses play an important role in the pathogenesis and diagnosis of multiple sclerosis (MS. A characteristic finding in patients with MS is a polyspecific intrathecal B cell response against neurotropic viruses, specifically against measles virus, rubella virus, and varicella zoster virus, also known as an MRZ reaction (MRZR. Here, we correlated from the routine clinical diagnostics individual IgG antibody indices (AIs of MRZR with magnetic resonance imaging (MRI findings in patients with first MS diagnosis. METHODS/RESULTS: MRZR was determined in 68 patients with a clinically isolated syndrome (CIS or early relapsing-remitting MS (RRMS. Absolute AI values for measles virus, rubella virus, and varicella zoster virus were correlated with T2 lesion load and gadolinium enhancing lesions on cerebral MRI (cMRI and cMRI combined with spinal MRI (sMRI. Measles virus AI correlated significantly with T2 lesion load on cMRI (p = 0.0312, Mann-Whitney U test and the sum of lesions on cMRI and sMRI (p = 0.0413. Varicella zoster virus AI also showed a correlation with T2 lesion load on cMRI but did not reach statistical significance (p = 0.2893. CONCLUSION: The results confirm MRZR as part of the polyspecific immune reaction in MS with possible prognostic impact on MRI and clinical parameters. Furthermore, the data indicate that intrathecal measles virus IgG production correlates with disease activity on cMRI and sMRI in patients with early MS.

  1. A novel trifunctional IgG-like bispecific antibody to inhibit HIV-1 infection and enhance lysis of HIV by targeting activation of complement

    Directory of Open Access Journals (Sweden)

    Tomlinson Stephen

    2010-06-01

    Full Text Available Abstract Background The complement system is not only a key component of innate immunity but also provides a first line of defense against invading pathogens, especially for viral pathogens. Human immunodeficiency virus (HIV, however, possesses several mechanisms to evade complement-mediated lysis (CoML and exploit the complement system to enhance viral infectivity. Responsible for this intrinsic resistance against complement-mediated virolysis are complement regulatory membrane proteins derived from the host cell that inherently downregulates complement activation at several stages of the cascade. In addition, HIV is protected from complement-mediated lysis by binding soluble factor H (fH through the viral envelope proteins, gp120 and gp41. Whereas inhibition of complement activity is the desired outcome in the vast majority of therapeutic approaches, there is a broader potential for complement-mediated inhibition of HIV by complement local stimulation. Presentation of the hypothesis Our previous studies have proven that the complement-mediated antibody-dependent enhancement of HIV infection is mediated by the association of complement receptor type 2 bound to the C3 fragment and deposited on the surface of HIV virions. Thus, we hypothesize that another new activator of complement, consisting of two dsFv (against gp120 and against C3d respectively linked to a complement-activating human IgG1 Fc domain ((anti-gp120 × anti-C3d-Fc, can not only target and amplify complement activation on HIV virions for enhancing the efficiency of HIV lysis, but also reduce the infectivity of HIV through blocking the gp120 and C3d on the surface of HIV. Testing the hypothesis Our hypothesis was tested using cell-free HIV-1 virions cultivated in vitro and assessment of virus opsonization was performed by incubating appropriate dilutions of virus with medium containing normal human serum and purified (anti-gp120 × anti-C3d-Fc proteins. As a control group, viruses

  2. The terminal complement complex is generated in chronic leg ulcers in the absence of protectin (CD59)

    DEFF Research Database (Denmark)

    Balslev, E; Thomsen, H K; Danielsen, L;

    1999-01-01

    hypertension leg ulcers. The deposition of complement, plasma complement regulators and expression of membrane regulators were detected by immunohistochemical methods, including immunofluorescence with antibodies against C3d, the terminal complement complex (TCC), vitronectin, clusterin, decay......-accelerating factor (CD55) and protectin (CD59). Eleven frozen biopsies from ischaemic leg ulcers, 10 biopsies from venous hypertension leg ulcers, and 10 biopsies from normal skin were studied. In 9 of 11 ischaemic and in 5 of 10 venous hypertension leg ulcers, marked staining for TCC was found around...... the capillaries, most often at the ulcer margin. No TCC staining was found in normal skin. Staining for TCC was always accompanied by staining for clusterin and vitronectin and C3d. In normal skin, CD59 was found on the elastic fibers in the dermis, on the muscle coat, the Schwann sheath and acinar cells...

  3. A Revised Mechanism for the Activation of Complement C3 to C3b

    OpenAIRE

    Rodriguez, Elizabeth; ,; Gor, Jayesh; Perkins, Stephen J.

    2014-01-01

    The solution structure of complement C3b is crucial for the understanding of complement activation and regulation. C3b is generated by the removal of C3a from C3. Hydrolysis of the C3 thioester produces C3u, an analog of C3b. C3b cleavage results in C3c and C3d (thioester-containing domain; TED). To resolve functional questions in relation to C3b and C3u, analytical ultracentrifugation and x-ray and neutron scattering studies were used with C3, C3b, C3u, C3c, and C3d, using the wild-type allo...

  4. A revised mechanism for the activation of complement C3 to C3b: a molecular explanation of a disease-associated polymorphism.

    OpenAIRE

    Rodriguez, E.; Nan, R.; Li, K; Gor, J.; Perkins, S J

    2015-01-01

    The solution structure of complement C3b is crucial for the understanding of complement activation and regulation. C3b is generated by the removal of C3a from C3. Hydrolysis of the C3 thioester produces C3u, an analog of C3b. C3b cleavage results in C3c and C3d (thioester-containing domain; TED). To resolve functional questions in relation to C3b and C3u, analytical ultracentrifugation and x-ray and neutron scattering studies were used with C3, C3b, C3u, C3c, and C3d, using the wild-type allo...

  5. Complement's participation in acquired immunity

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Leslie, Robert Graham Quinton

    2002-01-01

    of the B cell receptor for antigen (BCR), a complex composed of the iC3b/C3d fragment-binding complement type 2 receptor (CR2, CD21) and its signaling element CD19 and the IgG-binding receptor FcgammaRIIb (CD32). The positive or negative outcome of signaling through this triad is determined by the context...

  6. Identification and Characterization of Porcine Kobuvirus Variant Isolated from Suckling Piglet in Gansu Province, China

    OpenAIRE

    Xianzhu Xia; Yuwei Gao; Yongkun Zhao; Chuan Qin; Zhijun Yu; Songtao Yang; Tiecheng Wang; Yuanguo Li; Yicong Yu; Ying Ying; Shengtao Fan; Zheng Wang; Xiaolong Gao; Heting Sun

    2013-01-01

    Kobuviruses comprise three species, the Aichivirus A, Aichivirus B, and Aichivirus C (porcine kobuvirus). Porcine kobuvirus is endemic to pig farms and is not restricted geographically but, rather, is distributed worldwide. The complete genomic sequences of four porcine kobuvirus strains isolated during a diarrhea outbreak in piglets in the Gansu province of China were determined. Two of these strains exhibited variations relative to the traditional strains. The potential 3C/3D cleavage sites...

  7. The mechanism of Epstein-Barr virus infection in nasopharyngeal carcinoma cells.

    OpenAIRE

    Lin, C T; Lin, C. R.; Tan, G. K.; Chen, W.; Dee, A. N.; Chan, W Y

    1997-01-01

    To investigate the relationship between Epstein-Barr virus (EBV) and nasopharyngeal carcinoma (NPC) cells, we examined the pathway of EBV infection in NPC cell lines. We used immunolocalization to investigate the EBV receptor (C3d-R) and polymeric immunoglobulin receptor [secretory component (SC) protein]. We incubated IgA anti-EBV and EBV particles with NPC cells and observed the EBV DNA signal by in situ polymerase chain reaction hybridization and polymerase chain reaction plus Southern blo...

  8. Direct dissociative chemisorption of propane on Ir(110)

    International Nuclear Information System (INIS)

    We have employed molecular beam techniques to investigate the initial probability of direct dissociative chemisorption, Pd, and the intrinsic trapping probability, ξ, of C3H8, C3D8, and (CH3)2CD2 on Ir(110) as a function of beam translational energy, Ei, from 1.5 to 59 kcal/mol. For C3H8 and (CH3)2CD2, a measurable (≥0.02) initial probability of direct dissociative chemisorption is observed above a beam energy of approximately 7 kcal/mol. For C3D8 this energy is roughly 10 kcal/mol. Above these energies the initial probability of direct chemisorption of each of the isotopomers of propane increases nearly linearly with Ei, approaching a value of approximately Pd=0.48 at Ei=52 kcal/mol for C3H8 and (CH3)2CD2, and Pd=0.44 at Ei=59 kcal/mol for C3D8. This kinetic isotope effect for the direct chemisorption of C3D8 relative to C3H8 is smaller than that expected for a mechanism of H (or D) abstraction by tunneling through an Eckart barrier, suggesting a contribution of C endash C bond cleavage to direct chemisorption. The lack of a kinetic isotope effect for the direct chemisorption of (CH3)2CD2 relative to C3H8 indicates that 1 degree C endash H bond cleavage dominates over 2 degree C endash H bond cleavage during the direct chemisorption of propane on Ir(110). The trapping behavior of each of these isotopomers of propane is approximately identical as a function of Ei, with ξ>0.9 at Ei=1.5 kcal/mol, ξ=0.3 at Ei=20 kcal/mol, and ξi=40 kcal/mol. copyright 1996 American Institute of Physics

  9. Canada in 3D - Toward a Sustainable 3D Model for Canadian Geology from Diverse Data Sources

    Science.gov (United States)

    Brodaric, B.; Pilkington, M.; Snyder, D. B.; St-Onge, M. R.; Russell, H.

    2015-12-01

    Many big science issues span large areas and require data from multiple heterogeneous sources, for example climate change, resource management, and hazard mitigation. Solutions to these issues can significantly benefit from access to a consistent and integrated geological model that would serve as a framework. However, such a model is absent for most large countries including Canada, due to the size of the landmass and the fragmentation of the source data into institutional and disciplinary silos. To overcome these barriers, the "Canada in 3D" (C3D) pilot project was recently launched by the Geological Survey of Canada. C3D is designed to be evergreen, multi-resolution, and inter-disciplinary: (a) it is to be updated regularly upon acquisition of new data; (b) portions vary in resolution and will initially consist of four layers (surficial, sedimentary, crystalline, and mantle) with intermediary patches of higher-resolution fill; and (c) a variety of independently managed data sources are providing inputs, such as geophysical, 3D and 2D geological models, drill logs, and others. Notably, scalability concerns dictate a decentralized and interoperable approach, such that only key control objects, denoting anchors for the modeling process, are imported into the C3D database while retaining provenance links to original sources. The resultant model is managed in the database, contains full modeling provenance as well as links to detailed information on rock units, and is to be visualized in desktop and online environments. It is anticipated that C3D will become the authoritative state of knowledge for the geology of Canada at a national scale.

  10. Hyperhemolysis in a patient with β-thalassemia major

    Directory of Open Access Journals (Sweden)

    Morawakage R

    2009-01-01

    Full Text Available A case of hyperhemolysis in a 2-year-old boy with β thalassemia major was noted. After several transfusions, he developed hyperhemolysis with a positive (C3d only direct antiglobulin test (DAT and no clinically significant RBC allo- or auto-antibodies. (There was a weak cold antibody, showing a narrow thermal range. Because there was no significant improvement with steroid and immunoglobulin infusions, cyclophosphamide therapy was tried with notable success.

  11. Expression and modulation of complement receptor 2 (CR2/CD21 in the pathophysiology of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Rozaleen Dash

    2016-08-01

    Full Text Available Background: The involvement of B cells, complement activation and subsequent immune complex deposition has been implicated in the pathogenesis of rheumatoid arthritis (RA. Although the reduced expression of complement receptor 2 (CR2, CD21 on the B cells of RA patients is known for long, we aimed at determining the modulation and expression of CR2 on PBMC of healthy individuals and RA patients. Methods: Sixty controls and 57 RA patients were enrolled. PBMC-CR2 transcript levels were correlated with the levels of C3, C3d and circulating immune complexes (CIC in controls and patients and with DAS28 in patients only. CIC levels were determined by PEG precipitation, C3 levels by nephlometry and C3d levels were determined by enzyme linked immunosorbent assay (ELISA. Sixteen patients were recruited for 6 months follow up studies of transcript levels of PBMC correlated with DAS28 score. Appropriate statistical methods were used for the analyses of data. Results: Sixty controls and 57 RA patients were enrolled. PBMC-CR2 transcript levels were correlated with the levels of C3, C3d and circulating immune complexes (CIC in controls and patients and with DAS28 in patients only. CIC levels were determined by PEG precipitation, C3 levels by nephlometry and C3d levels were determined by enzyme linked immunosorbent assay (ELISA. Sixteen patients were recruited for 6 months follow up studies of transcript levels of PBMC correlated with DAS28 score. Appropriate statistical methods were used for the analyses of data. Conclusions: Low level of CR2 expression in patients may, thus, contribute significantly to the pathological manifestation of RA. Cause-effect relationships of the up regulation of CR2 on improvement of health condition with the pathophysiology of RA and their importance as putative disease markers is being confirmed.

  12. Tandem inhibin gene immunization to induce sheep twinning

    International Nuclear Information System (INIS)

    Inhibin (INH) is a type of glycoprotein hormone secreted by testicular sertoli cell and ovarian granulose cell. The protein is structurally a heterodimer composed of two sub-units α and β. The development of animal follicle and the fertility could be improved by inhibin immunization. However, the utilization of active and passive immunization of inhibin immunization in animal production was restricted due to its difficulty in preparation and the higher cost. The innovation and development of gene vaccine made it practical and effective to improve the reproductive performance of sheep through inhibin immunization. To improve the follicular development, ovarian ovulation and number animals farrowed, different types of inhibin gene vaccines were constructed and used to immunize mice, rats, sheep and cattle, but the immunization was not so effective as expected. In this sense, it is necessary to explore the novel methods in inhibin production and the new strategies in immune reproductive technology. To examine the feasibility of developing the inhibin gene as vaccine for sheep, we constructed the recombinant plasmid of tandem inhibin gene and investigated its effect in sheep twinning after the gene immunization. The synthetic DNA sequence of α-subunit (1 to 32) of inhibin in swine was used as the template to amplify the forward inhibin (FINH) gene sequence with the first double of primer. Then, the FINH was used as the template to amplify the reverse inhibin (RINH) gene sequence with the second double of primer. After the two sequences were combined, they connected with T carrier. They were transfected into the E.coli. by cultivating and multiplying, then the plasmid was extracted. After enzyme digestion, tandem inhibin gene and eukaryotic vector pcDNA3.1 were connected, the recombinant plasmid (pcDNA-DINH, pcDNA-double inhibin) expressed in the eukaryon would be obtained. The adjuvant, sheep complement 3d (sC3d), was cloned from the tissue in the liver of sheep by

  13. Biomechanical ToolKit: Open-source framework to visualize and process biomechanical data.

    Science.gov (United States)

    Barre, Arnaud; Armand, Stéphane

    2014-04-01

    C3D file format is widely used in the biomechanical field by companies and laboratories to store motion capture systems data. However, few software packages can visualize and modify the integrality of the data in the C3D file. Our objective was to develop an open-source and multi-platform framework to read, write, modify and visualize data from any motion analysis systems using standard (C3D) and proprietary file formats (used by many companies producing motion capture systems). The Biomechanical ToolKit (BTK) was developed to provide cost-effective and efficient tools for the biomechanical community to easily deal with motion analysis data. A large panel of operations is available to read, modify and process data through C++ API, bindings for high-level languages (Matlab, Octave, and Python), and standalone application (Mokka). All these tools are open-source and cross-platform and run on all major operating systems (Windows, Linux, MacOS X). PMID:24548899

  14. Systemic complement activation in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Hendrik P N Scholl

    Full Text Available Dysregulation of the alternative pathway (AP of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD, the leading cause of blindness in the elderly. To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood plasma were determined together with disease-associated genetic markers in AMD patients. Plasma concentrations of activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor D were quantified in patients (n = 112 and controls (n = 67. Subjects were analyzed for single nucleotide polymorphisms in factor H (CFH, factor B-C2 (BF-C2 and complement C3 (C3 genes which were previously found to be associated with AMD. All activation products, especially markers of chronic complement activation Ba and C3d (p<0.001, were significantly elevated in AMD patients compared to controls. Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population. In both the controls' and AMD patients' group, the protein markers of complement activation were correlated with CFH haplotypes.This study is the first to show systemic complement activation in AMD patients. This suggests that AMD is a systemic disease with local disease manifestation at the ageing macula. Furthermore, the data provide evidence for an association of systemic activation of the alternative complement pathway with genetic variants of CFH that were previously linked to AMD susceptibility.

  15. Ligation of the functional domain of complement receptor type 2 (CR2, CD21) is relevant for complex formation in T cell lines.

    Science.gov (United States)

    Prodinger, W M; Larcher, C; Schwendinger, M; Dierich, M P

    1996-04-01

    We investigated the potential of CD21, the complement receptor type 2, to form receptor complexes with other membrane molecules on T cell lines. CD21 from T cell lines transformed with human T cell leukemia virus type I (MT2, HUT-102, C5.MJ, Mondi, and C91.PL) and T cell lines that were not virus transformed was analyzed by coprecipitation following cell lysis with digitonin. mAbs binding to functional and nonfunctional epitopes of CD21 and a polyclonal antiserum against its intracellular portion precipitated CD21, which was indistinguishable from CD21 on B cell lines. In contrast to B cells, where CD21 is complexed with CD19 and CD81 (target of anti-proliferative Ab 1) or, alternatively, with CD35 (CR1), no surface molecules could be coprecipitated with three of four mAbs from these T cell lines. Therefore, we assume that CD21 is not part of a preformed complex in T cell lines. OKB7, the only mAb directed against the functional C3d binding site, coprecipitated two proteins of 105 and 55 Mr with CD21 from MT2 and Mondi cells and from the T cell lines Jurkat E6-1 and SupT1. These bands were also recovered with CD21 precipitated from MT2 cells with C3d bound to Sepharose via the internal thioester, but were absent in CD21-expressing B cell lines. As C3d and OKB7 are functional ligands for B cells, we propose that upon ligation on T cells, CD21 associates with molecules of 105/55 Mr in the plasma membrane. Whether this is the first event of a signal delivered to the T cell is under current investigation. PMID:8786322

  16. Structural and functional analysis of CR2/EBV receptor by means of monoclonal antibodies and limited tryptic digestion.

    Science.gov (United States)

    Petzer, A L; Schulz, T F; Stauder, R; Eigentler, A; Myones, B L; Dierich, M P

    1988-01-01

    The receptor for the C3d fragment of the third component of complement, CR2, has recently been shown also to act as the receptor for the Epstein-Barr virus (EBV) and to be involved in the control of B-cell proliferation. In order to define functionally important domains on this molecule, we produced monoclonal antibodies to several distinct epitopes. CR2 was purified from a NP-40 lysate of human tonsils by a new method involving sequential chromatography on lentil lectin Sepharose 4B and DEAE-Sephadex and used to immunize mice. After fusion we obtained four stable hybridoma lines producing antibody to CR2. Specificity of these antibodies for CR2 was ascertained by immunofluorescence analysis on a panel of various cells known to possess CR2, by their reactivity in a recently described ELISA for C3 receptors, by Western blotting with purified CR2 and immunoprecipitation from 125I-labelled Raji cells. These four antibodies were found to recognize three distinct epitopes localized on the same fragments of 95,000, 72,000, 50,000, 32,000 and 28,000 MW obtained after mild tryptic digestion of CR2. The 72,000 MW fragment contains the binding site for C3d. Two monoclonal antibodies recognizing the same epitope did not inhibit the binding of C3d-coated sheep erythrocytes to Raji cells, whereas the other two antibodies against distinct epitopes did inhibit in the presence of a second antibody. All four monoclonal antibodies stimulated the proliferation of human peripheral blood B cells. PMID:2448232

  17. Role of intraoperative Iso-C based navigation in challenging spine trauma

    Directory of Open Access Journals (Sweden)

    Jaiswal Ashish

    2007-01-01

    Full Text Available Background: Pedicle screw fixation is the most preferred method of stabilizing unstable spinal fractures. Pedicle screw placement may be difficult in presence of fractured posterior elements, deformed spine, gross instability and spinal pathology. Challenging spine-fracture fixation is defined as the presence of one or more of the following: 1 obscured topographical landmarks as in ankylosing spondylitis, 2 fractures in occipitocervical or cervicothoracic regions and 3 preexisting altered spinal alignment. We report a series of pedicle screw insertion with guidance of navigation in difficult fixation problems.. Materials and Methods: Fourteen patients [hangman′s fracture (n=3, odontoid fracture (n=4, C1C2 fracture (n=1 and spinal fracture with coexistent ankylosing spondylitis (n=6] underwent posterior stabilization. Intraoperatively after surgical exposure, images were acquired by Iso-C 3D C-arm and transferred to navigation system. Instrumentation was performed with navigational assistance. Postoperatively, placements of pedicle screws were evaluated with radiographs and CT scan. Results: Sixty-seven pedicle screws (cervical, n=33; thoracic, n=6; lumbar, n=26; sacral n=2 and 15 lateral mass screws were inserted with navigation guidance. The average time of image data acquisition by Iso-C 3D C-arm and its transfer to workstation was 4 minutes (range, 2-6 minutes. Postoperative CT scan revealed ideal placement of screws in 63 pedicles (94%, grade 1 cortical breaches (< 2 mm in 3 pedicles (4.5% and grade 2 cortical breach (2-4 mm in one pedicle (1.5%. There were no neurovascular complications. Deep infection was encountered in one case, which settled with debridement. Conclusions: Intraoperative Iso-C 3D C-arm based navigation is a useful adjunct while stabilizing challenging spinal trauma, rendering feasibility, accuracy and safety of pedicle screw placement even in difficult situations.

  18. Molecular basis of hereditary C3 deficiency.

    OpenAIRE

    Botto, M.; Fong, K. Y.; So, A K; Rudge, A; Walport, M.J. (Mark J.)

    1990-01-01

    Hereditary deficiency of complement component C3 in a 10-yr-old boy was studied. C3 could not be detected by RIA of serum from the patient. Segregation of C3 S and C3 F allotypes within the family confirmed the presence of a null gene for C3, for which the patient was homozygous. 30 exons have been characterized, spanning the entire beta chain of C3 and the alpha chain as far as the C3d region. Sequence analysis of the exons derived from the C3 null gene showed no abnormalities in the coding ...

  19. Complement activation and HLA-B27.

    OpenAIRE

    Meri, S.; Partanen, J; Leirisalo-Repo, M; Repo, H

    1988-01-01

    The efficiency of complement activation was studied in sera from HLA-B27 positive and negative subjects (27 with previous yersinia arthritis and 35 controls). Activation of complement with zymosan induced higher mean levels of the anaphylatoxin C3a in HLA-B27 positive sera (mean (SD) 7.40 (1.66) mg/l) than in HLA-B27 negative sera (6.41 (1.79) mg/l). Similarly, higher levels of C3d,g, another C3 breakdown fragment, were obtained in HLA-B27 positive sera after Escherichia coli 0111:B4 lipopoly...

  20. Activity and activation of the complement system in patients being operated on for cancer of the colon

    DEFF Research Database (Denmark)

    Baatrup, G; Qvist, N; Junker, A;

    1994-01-01

    system to fix C3b and C4b was restored to baseline nine days postoperatively. Concentration of C3d was significantly higher in serum from tumour venous blood compared with that from peripheral blood during operation. CONCLUSION: The presence of complement activation products in the general circulation...... reflects local activation of the complement system in the vicinity of the tumour, but this may have been influenced by tissue necrosis or subclinical infection. Haemodilution causes a significant reduction in the capacity of the complement system during operation, whereas inhibitory factors associated with...

  1. Synthesis of thienyl analogues of PCBM and investigation of morphology of mixtures in P3HT

    Directory of Open Access Journals (Sweden)

    2008-09-01

    Full Text Available Novel [6,6]-phenyl-C61-butyric acid methyl ester (PCBM analogues containing benzo[b]thiophene (3a, 3b and thieno[3,2-b]thiophene (3c, 3d were synthesized and characterized. The morphology of the thin films prepared from the mixtures of these methanofullerenes with regioregular poly(3-hexylthiophene (P3HT was investigated by AFM measurement and UV-Vis absorption spectroscopy. A solubility test of these methanofullerenes was performed by using dichloromethane as a solvent. es-TThCBM (3d exhibited 1.4 times greater solubility in dichloromethane than PCBM.

  2. Secondary metabolites from nudibranchs Tambja stegosauriformis, Hypselodoris lajenis and Okenia zoobotryon and from bryozoans Zoobotryon verticillatum and Bugula dentata from the Brazilian coastline

    International Nuclear Information System (INIS)

    The chemical investigation of the MeOH extract from the bryozoan B. dentata MeOH yielded tambjamines A (1), C (3), D (4), K (6), aldehyde 8 and the new tambjamine J1(9), while the extract of its predator, the nudibranch Tambja stegosauriformis, yielded tambjamines C and K, along with aldehyde 8. Furodisinin lactone (11) was isolated from the nudibranch Hypselodoris lajensis, a compound previously isolated from Dysidea sponges. The alkaloid 2,5,6-tribromo-N-methylgramine (12) was isolated from the nudibranch Okenia zoobotryon and from its prey, the bryozoan Zoobotryon verticillatum, the only source of 12 previously known. (author)

  3. 求整数部分值的七法(初一、初二、初三)

    Institute of Scientific and Technical Information of China (English)

    王用燮

    2006-01-01

    1.直接计算例1 积(1+(1/(1×3))(1+(1/(2×4)) (1+(1/3×5))(1+(1/4×6))…(1+(1/98×100)) (1+(1/99×101))的值的整数部分为( ) (A)1. (B)2. (C)3. (D)4. (91年广州等五市初中联赛) 解原式=

  4. Secondary metabolites from nudibranchs Tambja stegosauriformis, Hypselodoris lajenis and Okenia zoobotryon and from bryozoans Zoobotryon verticillatum and Bugula dentata from the Brazilian coastline; Metabolitos secundarios dos nudibranquios Tambja stegosauriformis, Hypselodoris lajensis e Okenia zoobotryon e dos briozoarios Zoobotryon verticillatum e Bugula dentata da costa do Brasil

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Fabio R.; Berlinck, Roberto G.S. [Universidade de Sao Paulo (IQSC/USP), Sao Carlos, SP (Brazil). Inst. de Quimica; Rodrigues Filho, Edson; Veloso, Katyuscya; Ferreira, Antonio G. [Universidade Federal de Sao Carlos (UFSCAR), SP (Brazil). Dept. de Quimica; Padula, Vinicius, E-mail: rgsberlinck@iqsc.usp.br [Zoologische Staatssammlung Muenchen, Mollusca Sektion, Muenchen (Germany)

    2012-07-01

    The chemical investigation of the MeOH extract from the bryozoan B. dentata MeOH yielded tambjamines A (1), C (3), D (4), K (6), aldehyde 8 and the new tambjamine J1(9), while the extract of its predator, the nudibranch Tambja stegosauriformis, yielded tambjamines C and K, along with aldehyde 8. Furodisinin lactone (11) was isolated from the nudibranch Hypselodoris lajensis, a compound previously isolated from Dysidea sponges. The alkaloid 2,5,6-tribromo-N-methylgramine (12) was isolated from the nudibranch Okenia zoobotryon and from its prey, the bryozoan Zoobotryon verticillatum, the only source of 12 previously known. (author)

  5. Detachment of Human Immunodeficiency Virus Type 1 from Germinal Centers by Blocking Complement Receptor Type 2

    OpenAIRE

    Kacani, Laco; Prodinger, Wolfgang M.; Sprinzl, Georg M.; Michael G Schwendinger; Spruth, Martin; Stoiber, Heribert; Döpper, Susanne; Steinhuber, Sabine; Steindl, Franz; Manfred P Dierich

    2000-01-01

    After the transition from the acute to the chronic phase of human immunodeficiency virus (HIV) infection, complement mediates long-term storage of virions in germinal centers (GC) of lymphoid tissue. The contribution of particular complement receptors (CRs) to virus trapping in GC was studied on tonsillar specimens from HIV-infected individuals. CR2 (CD21) was identified as the main binding site for HIV in GC. Monoclonal antibodies (MAb) blocking the CR2-C3d interaction were shown to detach 6...

  6. Reflection of disease activity in rheumatoid arthritis by indices of activation of the classical complement pathway.

    OpenAIRE

    Makinde, V A; Senaldi, G; Jawad, A S; Berry, H; Vergani, D

    1989-01-01

    Levels of C4d, a fragment of C4 generated during activation of the classical complement pathway, were measured in the plasma of 77 patients with rheumatoid arthritis and 30 healthy subjects. Disease activity was judged according to Ritchie's articular index to be mildly active in 31 (group 1), moderately active in 29 (group 2), and severely active in 17 patients (group 3). Plasma levels of C3d, a fragment of C3, and serum levels of C4, C3, and immune complexes were also measured. The ratios C...

  7. Correlation of systemic lupus erythematosus disease activity with classical complement (CH50 function and related protein levels

    Directory of Open Access Journals (Sweden)

    Salesi M

    2008-09-01

    Full Text Available "nBackground: The components of the classical complement pathway play an important role in the pathogenesis of systemic lupus erythematosus (SLE and are reportedly useful biomarkers of disease activity. In this study, we evaluate disease activity, complement function (total hemolytic complement, CH50 and complement protein levels (C3, C4, C3d, C4d, SC5b-9, comparing the results of patients with active disease versus those with inactive disease."n"nMethods: This cross-sectional study included 78 hospitalized women with SLE, 24 of whom were in the active group, with SLE disease activity indexes (SLEDAI.2K of >6, and 54 in the inactive group, with SLEDAI.2K of ≤6. Serum CH50 was measured using a red blood cell hemolytic assay. C3 and C4 levels were determined by nephlometry and plasma levels of C3d, C4d, SC5b-9 by ELISA. The data were statistically analyzed using SPSS."n"nResults: The mean (±standard error C4d levels of the inactive group were significantly higher than those of the active group (23.39±1.1µg/ml and 16.9±1.6µg/ml, respectively; p=0.003. There was also a significant correlation between C3 and C4 levels (p=0.807. The mean values of the other proteins (C3, C4, CH50, SC5b-9, and C3d circulating immune complex concentrations were not significantly different between the inactive group vs. the active group: 89.35±6.8 vs. 85.54±7.6mg/dl, 18.33±2.3 vs. 20.45±2.4mg/dl, 149.03±4.3 vs. 157±4.3U, 1414.4±114.94 vs. 1471.1±216.9ng/ml, 9.43±0.96 vs. 13.31±3.16µgEq/ml, respectively (p>0.05."n"nConclusions: According to our results, C4d levels may be used as a biomarker of disease activity. The significant correlation between C3 and C4 may confirm the activity of the classical pathway in SLE patients."n"nKeywords: Systemic lupus erythematosus, CH50, C3, C4, C3d, C4d, SC5b-9, inactive, flare.

  8. Relation of putative thioester bond in C3 to activation of the alternative pathway and the binding of C3b to biological targets of complement

    OpenAIRE

    1980-01-01

    The reaction of [14C]methylamine with native human C3 led to the stoichiometric incorporation of methylamine, loss of hemolytic activity, and the concomitant exposure of a sulfhydryl group that could be labeled with [14C]iodoacetamide. Both labeled sites were located in the C3d portion of the alpha-chain, which is known to contain the metastable binding of C3b. The methylamine-modified C3 [C3(CH3NH2)] was shown to exhibit many of the functional properties of C3b, although the C3a portion of t...

  9. Glomerular C3c localization indicates ongoing immune deposit formation and complement activation in experimental glomerulonephritis.

    OpenAIRE

    Schulze, M.; Pruchno, C. J.; Burns, M.; Baker, P. J.; R. J. Johnson; Couser, W G

    1993-01-01

    In antibody-mediated glomerular disease, deposits of C3 (C3b) are common and are degraded by factor I to C3c and C3d. However, the kinetics of C3b degradation in glomerulonephritis have not been defined. To do this, we studied three models of complement-dependent glomerulonephritis with established C3 deposits (passive Heymann nephritis, cationized immunoglobulin G membranous nephropathy, and concanavalin A-anticoncanavalin A glomerulonephritis). C3b deposition was halted by administration of...

  10. Zinc-induced self-association of complement C3b and Factor H: implications for inflammation and age-related macular degeneration.

    OpenAIRE

    Nan, R.; Tetchner, S; Rodriguez, E.; Pao, P. J.; Gor, J.; Lengyel, I; Perkins, S J

    2013-01-01

    The sub-retinal pigment epithelial deposits (sRPEds) that are a hallmark of age-related macular degeneration (AMD) contain both C3b and mM levels of zinc. C3 is the central protein of complement, while C3u is formed by the spontaneous hydrolysis of the thioester bridge in C3. During activation, C3 is cleaved to form active C3b, then C3b is inactivated by Factor I and Factor H to form the C3c and C3d fragments. The interaction of zinc with C3 was quantified using analytical ultracentrifugation...

  11. Unique role of the complement receptor CR1 in the degradation of C3b associated with immune complexes

    OpenAIRE

    1982-01-01

    The main finding of this paper is that CR1, the membrane receptor for C3b and C4b, together with C3b/C4b-inactivator (I), degrades C3b bound to immune complexes (C3b*). Two fragments are generated: C3c, which is released from the immune complexes, and C3d*. The C3c fragment released from the cell intermediate EAC1423b prepared with 125I-C3 was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and radioautography. It has a 135,000 mol wt and contains disulfide bo...

  12. Zinc-induced Self-association of Complement C3b and Factor H

    OpenAIRE

    Nan, Ruodan; Tetchner, Stuart; Rodriguez, Elizabeth; Pao, Po-Jung; Gor, Jayesh; Lengyel, Imre; Perkins, Stephen J.

    2013-01-01

    The sub-retinal pigment epithelial deposits that are a hallmark of age-related macular degeneration contain both C3b and millimolar levels of zinc. C3 is the central protein of complement, whereas C3u is formed by the spontaneous hydrolysis of the thioester bridge in C3. During activation, C3 is cleaved to form active C3b, then C3b is inactivated by Factor I and Factor H to form the C3c and C3d fragments. The interaction of zinc with C3 was quantified using analytical ultracentrifugation and ...

  13. Bioactive Constituents from the Aerial Parts of Lippia triphylla

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    2015-12-01

    Full Text Available Five new compounds, lippianosides A (1, B (2, C (3, D (4, and E (5, along with 26 (6–31 known ones were obtained from the 95% EtOH extract of Lippia triphylla (L. triphylla aerial parts collected from Rwanda, Africa. Among the known compounds, 11 and 17–30 were isolated from the Lippia genus for the first time. In addition, 12, 13, and 16 were firstly obtained from this species. The structures of them were elucidated by chemical and spectroscopic methods. The antioxidant and triglyceride accumulation inhibition effects of the 31 compounds were examined in L6 cells and HepG2 cells, respectively.

  14. Crystal structure of the antigen-binding fragment of a monoclonal antibody specific for the multidrug-resistance-linked ABC transporter human P-glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Esser, Lothar; Shukla, Suneet; Zhou, Fei; Ambudkar, Suresh V.; Xia, Di

    2016-07-27

    P-glycoprotein (P-gp) is a polyspecific ATP-dependent transporter linked to multidrug resistance in cancers that plays important roles in the pharmacokinetics of a large number of drugs. The drug-resistance phenotype of P-gp can be modulated by the monoclonal antibody UIC2, which specifically recognizes human P-gp in a conformation-dependent manner. Here, the purification, sequence determination and high-resolution structure of the Fab fragment of UIC2 (UIC2/Fab) are reported. Purified UIC2/Fab binds human P-gp with a 1:1 stoichiometry. Crystals of UIC2/Fab are triclinic (space groupP1), with unit-cell parametersa= 40.67,b= 44.91,c= 58.09 Å, α = 97.62, β = 99.10, γ = 94.09°, and diffracted X-rays to 1.6 Å resolution. The structure was determined by molecular replacement and refined to 1.65 Å resolution. The asymmetric unit contains one molecule of UIC2/Fab, which exhibits a positively charged antigen-binding surface, suggesting that it might recognize an oppositely charged extracellular epitope of P-gp.

  15. Development of Conformation Independent Computational Models for the Early Recognition of Breast Cancer Resistance Protein Substrates

    Directory of Open Access Journals (Sweden)

    Melisa Edith Gantner

    2013-01-01

    Full Text Available ABC efflux transporters are polyspecific members of the ABC superfamily that, acting as drug and metabolite carriers, provide a biochemical barrier against drug penetration and contribute to detoxification. Their overexpression is linked to multidrug resistance issues in a diversity of diseases. Breast cancer resistance protein (BCRP is the most expressed ABC efflux transporter throughout the intestine and the blood-brain barrier, limiting oral absorption and brain bioavailability of its substrates. Early recognition of BCRP substrates is thus essential to optimize oral drug absorption, design of novel therapeutics for central nervous system conditions, and overcome BCRP-mediated cross-resistance issues. We present the development of an ensemble of ligand-based machine learning algorithms for the early recognition of BCRP substrates, from a database of 262 substrates and nonsubstrates compiled from the literature. Such dataset was rationally partitioned into training and test sets by application of a 2-step clustering procedure. The models were developed through application of linear discriminant analysis to random subsamples of Dragon molecular descriptors. Simple data fusion and statistical comparison of partial areas under the curve of ROC curves were applied to obtain the best 2-model combination, which presented 82% and 74.5% of overall accuracy in the training and test set, respectively.

  16. Stress regulated members of the plant organic cation transporter family are localized to the vacuolar membrane

    Directory of Open Access Journals (Sweden)

    Koch Wolfgang

    2008-07-01

    Full Text Available Abstract Background In Arabidopsis six genes group into the gene family of the organic cation transporters (OCTs. In animals the members of the OCT-family are mostly characterized as polyspecific transporters involved in the homeostasis of solutes, the transport of monoamine neurotransmitters and the transport of choline and carnitine. In plants little is known about function, localisation and regulation of this gene family. Only one protein has been characterized as a carnitine transporter at the plasma membrane so far. Findings We localized the five uncharacterized members of the Arabidopsis OCT family, designated OCT2-OCT6, via GFP fusions and protoplast transformation to the tonoplast. Expression analysis with RNA Gel Blots showed a distinct, organ-specific expression pattern of the individual genes. With reporter gene fusion of four members we analyzed the tissue specific distribution of OCT2, 3, 4, and 6. In experiments with salt, drought and cold stress, we could show that AtOCT4, 5 and 6 are up-regulated during drought stress, AtOCT3 and 5 during cold stress and AtOCT 5 and 6 during salt stress treatments. Conclusion Localisation of the proteins at the tonoplast and regulation of the gene expression under stress conditions suggests a specific role for the transporters in plant adaptation to environmental stress.

  17. Omics Meets Biology: Application to the Design and Preclinical Assessment of Antivenoms

    Directory of Open Access Journals (Sweden)

    Juan J. Calvete

    2014-12-01

    Full Text Available Snakebite envenoming represents a neglected tropical disease that has a heavy public health impact worldwide, mostly affecting poor people involved in agricultural activities in Africa, Asia, Latin America and Oceania. A key issue that complicates the treatment of snakebite envenomings is the poor availability of the only validated treatment for this disease, antivenoms. Antivenoms can be an efficacious treatment for snakebite envenoming, provided they are safe, effective, affordable, accessible and administered appropriately. The shortage of antivenoms in various regions, particularly in Sub-Saharan Africa and some parts of Asia, can be significantly alleviated by optimizing the use of current antivenoms and by the generation of novel polyspecific antivenoms having a wide spectrum of efficacy. Complementing preclinical testing of antivenom efficacy using in vivo and in vitro functional neutralization assays, developments in venomics and antivenomics are likely to revolutionize the design and preclinical assessment of antivenoms by being able to test new antivenom preparations and to predict their paraspecific neutralization to the level of species-specific toxins.

  18. Syndromic approach to treatment of snake bite in Sri Lanka based on results of a prospective national hospital-based survey of patients envenomed by identified snakes.

    Science.gov (United States)

    Ariaratnam, Christeine A; Sheriff, Mohamed H Rezvi; Arambepola, Carukshi; Theakston, R David G; Warrell, David A

    2009-10-01

    Of 860 snakes brought to 10 hospitals in Sri Lanka with the patients they had bitten, 762 (89%) were venomous. Russell's vipers (Daboia russelii) and hump-nosed pit vipers (Hypnale hypnale) were the most numerous and H. hypnale was the most widely distributed. Fifty-one (6%) were misidentified by hospital staff, causing inappropriate antivenom treatment of 13 patients. Distinctive clinical syndromes were identified to aid species diagnosis in most cases of snake bite in Sri Lanka where the biting species is unknown. Diagnostic sensitivities and specificities of these syndromes for envenoming were 78% and 96% by Naja naja, 66% and 100% by Bungarus caeruleus, 14% and 100% by Daboia russelii, and 10% and 97% by Hypnale hypnale, respectively. Although only polyspecific antivenoms are used in Sri Lanka, species diagnosis remains important to anticipate life-threatening complications such as local necrosis, hemorrhage and renal and respiratory failure and to identify likely victims of envenoming by H. hypnale who will not benefit from existing antivenoms. The technique of hospital-based collection, labeling and preservation of dead snakes brought by bitten patients is recommended for rapid assessment of a country's medically-important herpetofauna.

  19. Common spectrum of polypeptides occurs in secretion granule membranes of different exocrine glands

    International Nuclear Information System (INIS)

    A highly purified membrane preparation from rat parotid secretion granules has been used as a comparative probe to examine the extent of compositional overlap in granule membranes of three other exocrine secretory tissues - pancreatic, lacrimal, and submandibular - from several standpoints. First, indirect immunofluorescent studies using a polyclonal polyspecific anti-parotid granule membrane antiserum has indicated a selective staining of granule membrane profiles in all acinar cells of all tissues. Second, highly purified granule membrane subfractions have been isolated from each exocrine tissue; comparative two-dimensional (isoelectric focusing; SDS) PAGE of radioiodinated granule membranes has identified 10-15 polypeptides of identical pI and apparent molecular mass. These species are likely to be integral membrane components since they are not extracted by either saponin-sodium sulfate or sodium carbonate (pH 11.5) treatments, and they do not have counterparts in the granule content. Finally, the identity among selected parotid and pancreatic radioiodinated granule membrane polypeptides has been documented using two-dimensional peptide mapping of chymotryptic and tryptic digests. These findings clearly indicate that exocrine secretory granules, irrespective of the nature of stored secretion, comprise a type of vesicular carrier with a common (and probably refined) membrane composition. Conceivably, the polypeptides identified carry out general functions related to exocrine secretion

  20. Human interleukin 2

    International Nuclear Information System (INIS)

    Using polyclonal and monoclonal antibodies to human recombinant IL-2, the authors developed a sensitive radioimmunoassay (RIA) for quantitation of human IL-2. In this assay, microtitration plates pre-coated with an anti-rIL-2 monoclonal antibody are incubated with serial dilutions of test samples. Captured IL-2 is quantitated by adding an affinity-purified rabbit anti-rIL-2 antibody followed by an 125I-labeled goat anti-rabbit IgG. Antibodies to chemically, synthesized IL-2 peptide could replace the polyspecific rabbit anti-rIL-2 antibody. This configuration was more sensitive than others tested. Serum or plasma fluids, however, inhibited the assay, reducing its sensitivity by approximately 5-fold. This RIA correlated well with the conventional bioassay in measuring IL-2 levels in sera from IL-2-treated patients. This, and similar, RIAs may serve as a useful adjunct or alternative to the conventional IL-2 bioassay in detecting and quantitating human IL-2 in culture supernatants and clinical samples. (Auth.)

  1. Survey on intestinal helminth fauna of woodcocks (Scolopax rusticola) in Italy.

    Science.gov (United States)

    Paoletti, Barbara; Di Cesare, Angela; Iorio, Raffaella; Tavaglione, Domenico; Bartolini, Roberto; Gatti, Antonio

    2016-06-30

    Every year populations of the European woodcock (Scolopax rusticola) migrate from Central and Northern Europe to the Mediterranean basin. South of Italy is one of the most common wintering site for this species. Given that information on parasites of woodcocks is scarce, the present study aimed at identifying the parasitic species affecting woodcocks migrating in Italy. The gastrointestinal tract of 206 woodcocks hunted in Southern Italy was removed and examined for parasites. From each animal a faecal sample was analysed by flotation test. The necropsy showed the presence of cestodes, i.e. Paricterotaenia paradoxa (59.4%) and Aploparaksis filum (49.5%), and of acanthocephalan Prosthorhynchus scolopacidis (22.4%). In one bird we also detected Parastrigea robusta, which is a trematode until now reported only in mallards (Anas platyrhynchos). Mixed infections (i.e., polyspecific infections) were detected in 53 (27.6%) animals. The most common were those caused by A. filum and P. paradoxa (12.5%), and by P. paradoxa and P. scolopacidis (8.3%). Copromicroscopic examinations revealed the presence of eggs belonging to nematodes Syngamus spp. (1.94%) in 4 woodcocks and of eggs of cestodes Aploparaksis spp. (37.86%) in 78 woodcocks. The present results fill a gap in the knowledge on parasites affecting woodcocks. PMID:27188826

  2. Preclinical assessment of the neutralizing capacity of antivenoms produced in six Latin American countries against medically-relevant Bothrops snake venoms.

    Science.gov (United States)

    Segura, A; Castillo, M C; Núñez, V; Yarlequé, A; Gonçalves, L R C; Villalta, M; Bonilla, C; Herrera, M; Vargas, M; Fernández, M; Yano, M Y; Araújo, H P; Boller, M A A; León, P; Tintaya, B; Sano-Martins, I S; Gómez, A; Fernández, G P; Geoghegan, P; Higashi, H G; León, G; Gutiérrez, J M

    2010-11-01

    Species of the genus Bothrops induce the vast majority of snakebite envenomings in Latin America. A preclinical study was performed in the context of a regional network of public laboratories involved in the production, quality control and development of antivenoms in Latin America. The ability of seven polyspecific antivenoms, produced in Argentina, Brazil, Peru, Bolivia, Colombia and Costa Rica, to neutralize lethal, hemorrhagic, coagulant, defibrinogenating and myotoxic activities of the venoms of Bothrops neuwiedi (diporus) (Argentina), Bothrops jararaca (Brazil), B. neuwiedi (mattogrossensis) (Bolivia), Bothrops atrox (Peru and Colombia) and Bothrops asper (Costa Rica) was assessed using standard laboratory tests. Despite differences in the venom mixtures used in the immunization of animals for the production of these antivenoms, a pattern of extensive cross-neutralization was observed between these antivenoms and all the venoms tested, with quantitative differences in the values of effective doses. This study reveals the capacity of these antivenoms to neutralize, in preclinical tests, homologous and heterologous Bothrops venoms in Central and South America, and also highlight quantitative differences in the values of Median Effective Doses (ED50s) between the various antivenoms.

  3. Molecular docking characterizes substrate-binding sites and efflux modulation mechanisms within P-glycoprotein.

    Science.gov (United States)

    Ferreira, Ricardo J; Ferreira, Maria-José U; dos Santos, Daniel J V A

    2013-07-22

    P-Glycoprotein (Pgp) is one of the best characterized ABC transporters, often involved in the multidrug-resistance phenotype overexpressed by several cancer cell lines. Experimental studies contributed to important knowledge concerning substrate polyspecificity, efflux mechanism, and drug-binding sites. This information is, however, scattered through different perspectives, not existing a unifying model for the knowledge available for this transporter. Using a previously refined structure of murine Pgp, three putative drug-binding sites were hereby characterized by means of molecular docking. The modulator site (M-site) is characterized by cross interactions between both Pgp halves herein defined for the first time, having an important role in impairing conformational changes leading to substrate efflux. Two other binding sites, located next to the inner leaflet of the lipid bilayer, were identified as the substrate-binding H and R sites by matching docking and experimental results. A new classification model with the ability to discriminate substrates from modulators is also proposed, integrating a vast number of theoretical and experimental data. PMID:23802684

  4. A new Dendropsophus Fitzinger, 1843 (Anura: Hylidae) of the parviceps group from the lowlands of the Guiana Shield.

    Science.gov (United States)

    Fouquet, Antoine; Orrico, Victor Goyannes Dill; Ernst, Raffael; Blanc, Michel; Martinez, Quentin; Vacher, Jean-Pierre; Rodrigues, Miguel Trefaut; Ouboter, Paul; Jairam, Rawien; Ron, Santiago

    2015-12-01

    Many Amazonian frog species that are considered widely distributed may actually represent polyspecific complexes.. A minute tree frog from the Guiana Shield originally assigned to the allegedly widely distributed Dendropsophus brevifrons proved to be a yet undescribed species within the D. parviceps group. We herein describe this new species and present a phylogeny for the D. parviceps group. The new species is diagnosed from other Dendropsophus of the parviceps group by its small body size (19.6-21.7 mm in males, 22.1-24.5 mm in females), thighs dorsally dark grey with cream blotches without bright yellow patch, absence of dorsolateral and canthal stripe, and an advertisement call comprising trills (length 0.30-0.35 s) composed of notes emitted at a rate of 131-144 notes/s, generally followed by click series of 2-3 notes. Its tadpole is also singular by having fused lateral marginal papillae and absence of both labial teeth and submarginal papillae. Genetic distances (p-distance) are >5.3% on the 12S and >9.3% on the 16S from D. brevifrons, its closest relative. This species occurs from the Brazilian state of Amapá, across French Guiana and Suriname to central Guyana and is likely to also occur in adjacent Brazilian states and eastern Venezuela. This species is not rare but is difficult to collect because of its arboreal habits and seasonal activity peaks.

  5. Rigidity Emerges during Antibody Evolution in Three Distinct Antibody Systems: Evidence from QSFR Analysis of Fab Fragments.

    Directory of Open Access Journals (Sweden)

    Tong Li

    2015-07-01

    Full Text Available The effects of somatic mutations that transform polyspecific germline (GL antibodies to affinity mature (AM antibodies with monospecificity are compared among three GL-AM Fab pairs. In particular, changes in conformational flexibility are assessed using a Distance Constraint Model (DCM. We have previously established that the DCM can be robustly applied across a series of antibody fragments (VL to Fab, and subsequently, the DCM was combined with molecular dynamics (MD simulations to similarly characterize five thermostabilizing scFv mutants. The DCM is an ensemble based statistical mechanical approach that accounts for enthalpy/entropy compensation due to network rigidity, which has been quite successful in elucidating conformational flexibility and Quantitative Stability/Flexibility Relationships (QSFR in proteins. Applied to three disparate antibody systems changes in QSFR quantities indicate that the VH domain is typically rigidified, whereas the VL domain and CDR L2 loop become more flexible during affinity maturation. The increase in CDR H3 loop rigidity is consistent with other studies in the literature. The redistribution of conformational flexibility is largely controlled by nonspecific changes in the H-bond network, although certain Arg to Asp salt bridges create highly localized rigidity increases. Taken together, these results reveal an intricate flexibility/rigidity response that accompanies affinity maturation.

  6. Human lymphokine-activated killer cell system. V. Purified recombinant interleukin 2 activates cytotoxic lymphocytes which lyse both natural killer-resistant autologous and allogeneic tumors and trinitrophenyl-modified autologous peripheral blood lymphocytes

    International Nuclear Information System (INIS)

    Culture of human peripheral blood lymphocytes (PBL) in purified natural or recombinant interleukin 2 in the absence of exogenous antigen or mitogen causes the differentiation of nonlytic precursor cells into lymphokine-activated killers (LAK). A titration of purified Jurkat IL-2 (BRMP, FCRC, NIH) IL-2 showed that the relatively low concentration of 5 U/ml was optimal for LAK activation. When the responding PBL were pretreated with either mitomycin C or gamma irradiation, LAK activation did not occur, indicating that proliferation, in addition to differentiation, is required. The spectrum of target cells susceptible to LAK lysis in a 4-hr chromium-51-release assay includes fresh NK-resistant tumor cells and trinitrophenyl (TNP)-modified autologous PBL. Unmodified PBL are not lysed. Cold target inhibition studies indicated that LAK lysis of autologous TNP-PBL is totally inhibited by fresh tumors cells, and that tumor lysis is inhibited by TNP-PBL. Additionally, allogeneic tumors totally inhibit lysis of autologous tumor cells in other cold target studies. These results demonstrate that the lytic activity expressed by LAK is not HLA restricted, is not limited to tumor cells, and is polyspecific as indicated by the cross-reactive recognition of multiple target cell types in these cold target inhibition studies

  7. Use of the uteroglobin platform for the expression of a bivalent antibody against oncofetal fibronectin in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Elisa Ventura

    Full Text Available Escherichia coli is a robust, economic and rapid expression system for the production of recombinant therapeutic proteins. However, the expression in bacterial systems of complex molecules such as antibodies and fusion proteins is still affected by several drawbacks. We have previously described a procedure based on uteroglobin (UG for the engineering of very soluble and stable polyvalent and polyspecific fusion proteins in mammalian cells (Ventura et al. 2009. J. Biol. Chem. 284∶26646-26654. Here, we applied the UG platform to achieve the expression in E. coli of a bivalent human recombinant antibody (L19 toward the oncofetal fibronectin (B-FN, a pan-tumor target. Purified bacterial L19-UG was highly soluble, stable, and, in all molecules, the L19 moiety maintained its immunoreactivity. About 50-70% of the molecules were covalent homodimer, however after refolding with the redox couple reduced-glutathione/oxidized-glutathione (GSH/GSSG, 100% of molecules were covalent dimers. Mass spectrometry studies showed that the proteins produced by E. coli and mammalian cells have an identical molecular mass and that both proteins are not glycosylated. L19-UG from bacteria can be freeze-dried without any loss of protein and immunoreactivity. In vivo, in tumor-bearing mice, radio-iodinated L19-UG selectively accumulated in neoplastic tissues showing the same performance of L19-UG from mammalian cells. The UG-platform may represent a general procedure for production of various biological therapeutics in E. coli.

  8. Rigidity Emerges during Antibody Evolution in Three Distinct Antibody Systems: Evidence from QSFR Analysis of Fab Fragments.

    Science.gov (United States)

    Li, Tong; Tracka, Malgorzata B; Uddin, Shahid; Casas-Finet, Jose; Jacobs, Donald J; Livesay, Dennis R

    2015-07-01

    The effects of somatic mutations that transform polyspecific germline (GL) antibodies to affinity mature (AM) antibodies with monospecificity are compared among three GL-AM Fab pairs. In particular, changes in conformational flexibility are assessed using a Distance Constraint Model (DCM). We have previously established that the DCM can be robustly applied across a series of antibody fragments (VL to Fab), and subsequently, the DCM was combined with molecular dynamics (MD) simulations to similarly characterize five thermostabilizing scFv mutants. The DCM is an ensemble based statistical mechanical approach that accounts for enthalpy/entropy compensation due to network rigidity, which has been quite successful in elucidating conformational flexibility and Quantitative Stability/Flexibility Relationships (QSFR) in proteins. Applied to three disparate antibody systems changes in QSFR quantities indicate that the VH domain is typically rigidified, whereas the VL domain and CDR L2 loop become more flexible during affinity maturation. The increase in CDR H3 loop rigidity is consistent with other studies in the literature. The redistribution of conformational flexibility is largely controlled by nonspecific changes in the H-bond network, although certain Arg to Asp salt bridges create highly localized rigidity increases. Taken together, these results reveal an intricate flexibility/rigidity response that accompanies affinity maturation.

  9. Immune mechanisms of the radioprotective effects of ceruloplasmin

    International Nuclear Information System (INIS)

    Immunotropic features of ceruloplasmin (Cp) were examined and its capacity as radioprotector was estimated. Pulse radiolysis method was used to set the mechanism of elementary reactions, which were responsible for antioxidant activity and to demonstrate a particular role of reversible oxycomplexes Cp...O2. Within in vitro test-systems the effects of Cp were examined on the model of interaction between lymphocytes from Shelter staff which constantly contacts with ionizing radiation and autologous erythrocytes in rosset-forming phenomenon. Expression of this Index in the presence of antigens with known polyspecificity was determined (antigens were taken from cortical and pyramid sections of kidney, liver, lungs, myocard, pancreatic gland, grey matter and aorta). Simultaneously the presence of analogous autoantibodies was determined. It has been shown that Cp can reprogram the level of expression of immunovaluable receptors towards to norm. It has been also defined that Cp presence in blood irradiated in vitro (1-15 rem) promotes the masking of active centers of autoantibodies of different tissue specificity

  10. Strongyloides stercoralis and other Enteroparasites in Children at Uberlândia City, State of Minas Gerais, Brazil

    Directory of Open Access Journals (Sweden)

    Rodrigues Machado Eleuza

    1998-01-01

    Full Text Available To evaluate the rate of infection by Strongyloides stercoralis and other enteroparasites a survey was conducted in the city of Uberlândia, State of Minas Gerais, Brazil. A total of 900 stool samples from 300 children aging from four months to seven years, randomly selected in ten nursery schools from September 1994 to December 1995, were examined, both by the Baermann-Moraes and Lutz methods. Thirty nine children (13% were found to be infected by S. stercoralis, 64.1% were boys and 35.9% were girls. Taking all the enteroparasites as a whole the results of the survey pointed out that 265 (88.4% of the 300 children were infected by the following: Giardia lamblia, 78.3%; Ascaris lumbricoides, 15.3%; S. stercoralis, 13%; Hymenolepis nana, 6.7%; hookworms, 6%; Enterobius vermicularis, 4%; Hymenole-pis diminuta, 4% and Trichuris trichiura, 0.7%. From 265 infected children 64.5% were mono-infected, 27.2% were infected by two parasites and 8.3% had a poly-specific parasite burden. It was concluded that strongyloidiasis is hyperendemic in this area

  11. Machine learning-, rule- and pharmacophore-based classification on the inhibition of P-glycoprotein and NorA.

    Science.gov (United States)

    Ngo, T-D; Tran, T-D; Le, M-T; Thai, K-M

    2016-09-01

    The efflux pumps P-glycoprotein (P-gp) in humans and NorA in Staphylococcus aureus are of great interest for medicinal chemists because of their important roles in multidrug resistance (MDR). The high polyspecificity as well as the unavailability of high-resolution X-ray crystal structures of these transmembrane proteins lead us to combining ligand-based approaches, which in the case of this study were machine learning, perceptual mapping and pharmacophore modelling. For P-gp inhibitory activity, individual models were developed using different machine learning algorithms and subsequently combined into an ensemble model which showed a good discrimination between inhibitors and noninhibitors (acctrain-diverse = 84%; accinternal-test = 92% and accexternal-test = 100%). For ligand promiscuity between P-gp and NorA, perceptual maps and pharmacophore models were generated for the detection of rules and features. Based on these in silico tools, hit compounds for reversing MDR were discovered from the in-house and DrugBank databases through virtual screening in an attempt to restore drug sensitivity in cancer cells and bacteria.

  12. Intravenous administration of equine-derived whole IgG antivenom does not induce early adverse reactions in non-envenomed horses and cows.

    Science.gov (United States)

    Estrada, Ricardo; Herrera, María; Segura, Alvaro; Araya, Javier; Boschini, Carlos; Gutiérrez, José María; León, Guillermo

    2010-11-01

    Administration of antivenoms to treat snakebite envenomings has the potential risk of inducing early adverse reactions. The mechanisms involved in these reactions are unclear. In this study, polyspecific antivenom consisting of whole IgG purified from equine plasma by caprylic acid precipitation was administered intravenously to non-envenomed horses (n = 47) and cows (n = 20) at a dose of 0.4 mL/kg. It has been reported that, in humans, this formulation (administered at a dose of 0.4 mL/kg) induces mild noticeable early adverse reactions, such as fever, vomiting, diarrhea, urticaria, generalized rash, tachypnea or tachycardia, in about 15-20% of the patients. Unexpectedly, none of the animals receiving antivenom in our study showed any evidence of early adverse reaction. Moreover, no late adverse reactions, i.e. serum sickness, were observed during 40 days after antivenom administration. Unlike studies performed in envenomed humans, our present results were obtained in a group of non-envenomed individuals. It is concluded that, in addition to the physicochemical characteristics of the formulation, other unknown factors must determine the occurrence of adverse reactions in snakebite envenomed humans treated with equine-derived antivenoms.

  13. Pharmacological characterization and neutralization of the venoms used in the production of Bothropic antivenom in Brazil.

    Science.gov (United States)

    Camey, Kyoko U; Velarde, David T; Sanchez, Eladio F

    2002-05-01

    Some pharmacological effects of the venoms of five different Brazilian Bothrops species and a pool of these venoms (AgB) were quantified. The ability of polyspecific Bothropic antivenom produced at Fundação Ezequiel Dias (FUNED, Brazil) to neutralize the principal toxic and enzymatic activities was studied using in vivo and in vitro assays. The lethality, hemorrhagic, necrotizing, proteolytic, phospholipase, coagulant and fibrinolytic activities were measured for each of these venoms. Comparison of protein electrophoretic patterns showed significant differences such as the presence of common and also unique components. Furthermore, experimental studies revealed differences in their biological properties among individual samples. It was found that the Bothrops antivenom was highly effective in the neutralization of the toxic activities of all venoms tested. In addition, indirect ELISA was used to compare the antigenic cross-reactivity for each of the five Bothrops venoms as well as the venoms of B. atrox, B. leucurus and B. erythromelas which were not included in the antigenic pool (AgB). Therefore, the characterization of several toxic activities of snake venoms is necessary, if toxicity is to be properly evaluated. Results indicate that the Brazilian antivenom prepared at FUNED against Bothrops snakes is effective in neutralizing the main toxic effects of Bothrops venoms. PMID:11821121

  14. Preclinical assessment of the neutralizing capacity of antivenoms produced in six Latin American countries against medically-relevant Bothrops snake venoms.

    Science.gov (United States)

    Segura, A; Castillo, M C; Núñez, V; Yarlequé, A; Gonçalves, L R C; Villalta, M; Bonilla, C; Herrera, M; Vargas, M; Fernández, M; Yano, M Y; Araújo, H P; Boller, M A A; León, P; Tintaya, B; Sano-Martins, I S; Gómez, A; Fernández, G P; Geoghegan, P; Higashi, H G; León, G; Gutiérrez, J M

    2010-11-01

    Species of the genus Bothrops induce the vast majority of snakebite envenomings in Latin America. A preclinical study was performed in the context of a regional network of public laboratories involved in the production, quality control and development of antivenoms in Latin America. The ability of seven polyspecific antivenoms, produced in Argentina, Brazil, Peru, Bolivia, Colombia and Costa Rica, to neutralize lethal, hemorrhagic, coagulant, defibrinogenating and myotoxic activities of the venoms of Bothrops neuwiedi (diporus) (Argentina), Bothrops jararaca (Brazil), B. neuwiedi (mattogrossensis) (Bolivia), Bothrops atrox (Peru and Colombia) and Bothrops asper (Costa Rica) was assessed using standard laboratory tests. Despite differences in the venom mixtures used in the immunization of animals for the production of these antivenoms, a pattern of extensive cross-neutralization was observed between these antivenoms and all the venoms tested, with quantitative differences in the values of effective doses. This study reveals the capacity of these antivenoms to neutralize, in preclinical tests, homologous and heterologous Bothrops venoms in Central and South America, and also highlight quantitative differences in the values of Median Effective Doses (ED50s) between the various antivenoms. PMID:20621114

  15. Generation of a C3c specific monoclonal antibody and assessment of C3c as a putative inflammatory marker derived from complement factor C3

    DEFF Research Database (Denmark)

    Palarasah, Yaseelan; Skjødt, Karsten; Brandt, Jette;

    2010-01-01

    complex (C5b-C9) and quantification of complement split products by precipitation-in-gel techniques (e.g. C3d). We have developed a mouse monoclonal antibody (mAb) that is able to detect fluid phase C3c without interference from other products generated from the complement component C3. The C3c specific m......Ab was tested in different ELISA combinations with various types of in vitro activated sera and with plasma or serum samples from factor I deficient patients. The specificity of the mAb was evaluated in immunoprecipitation techniques and by analysis of eluted fragments of C3 after immunoaffinity...... chromatography. The C3c mAb was confirmed to be C3c specific, as it showed no cross-reactivity with native (un-cleaved) C3, with C3b, iC3b, or with C3d. Also, no significant reaction was observed with C3 fragments in factor I deficient sera or plasma. This antibody forms the basis for the generation of a robust...

  16. Phylogenetic and molecular analyses of human parainfluenza type 3 virus in Buenos Aires, Argentina, between 2009 and 2013: The emergence of new genetic lineages.

    Science.gov (United States)

    Goya, Stephanie; Mistchenko, Alicia Susana; Viegas, Mariana

    2016-04-01

    Despite that human parainfluenza type 3 viruses (HPIV3) are one of the leading causes of acute lower respiratory tract infections in children under five, there is no licensed vaccine and there is limited current information on the molecular characteristics of regional and global circulating strains. The aim of this study was to describe the molecular characterization of HPIV3 circulating in Buenos Aires. We performed a genetic and phylogenetic analysis of the HN glycoprotein gene. Between 2009 and 2013, 124 HPIV3-positive samples taken from hospitalized pediatric patients were analyzed. Four new genetic lineages were described. Among them, C1c and C3d lineages showed local circulation patterns, whereas C3e and C3f comprised sequences from very distant countries. Despite the diversity of the described genotypes, C3a and C3d predominated over the others, the latter was present during the first years of the study and it was progressively replaced by C3a. Molecular analyses showed 28 non-synonymous substitutions; of these, 13 were located in potentially predicted B-cell epitopes. Taken together, the emergence of genetic lineages and the information of the molecular characteristics of HN protein may contribute to the general knowledge of HPIV3 molecular epidemiology for future vaccine development and antiviral therapies. PMID:26780643

  17. Class 3 semaphorins expression and association with innervation and angiogenesis within the degenerate human intervertebral disc.

    Science.gov (United States)

    Binch, Abbie L A; Cole, Ashley A; Breakwell, Lee M; Michael, Anthony L R; Chiverton, Neil; Creemers, Laura B; Cross, Alison K; Le Maitre, Christine L

    2015-07-30

    Nerve and blood vessel ingrowth during intervertebral disc degeneration, is thought to be a major cause of low back pain, however the regulation of this process is poorly understood. Here, we investigated the expression and regulation of a subclass of axonal guidance molecules known as the class 3 semaphorins, and their receptors; plexins and neuropilins within human NP tissue and their regulation by pro-inflammatory cytokines. Importantly this determined whether semaphorin expression was associated with the presence of nerves and blood vessels in tissues from human intervertebral discs. The study demonstrated that semaphorin3A, 3C, 3D, 3E and 3F and their receptors were expressed by native NP cells and further demonstrated their expression was regulated by IL-1β but to a lesser extent by IL-6 and TNFα. This is the first study to identify sema3C, sema3D and their receptors within the nucleus pulposus of intervertebral discs. Immunopositivity shows significant increases in semaphorin3C, 3D and their receptor neuropilin-2 in degenerate samples which were shown to contain nerves and blood vessels, compared to non-degenerate samples without nerves and blood vessels. Therefore data presented here suggests that semaphorin3C may have a role in promoting innervation and vascularisation during degeneration, which may go on to cause low back pain.

  18. T lymphocyte expression of complement receptor 2 (CR2/CD21): a role in adhesive cell-cell interactions and dysregulation in a patient with systemic lupus erythematosus (SLE).

    Science.gov (United States)

    Levy, E; Ambrus, J; Kahl, L; Molina, H; Tung, K; Holers, V M

    1992-11-01

    Complement receptor 2 (CR2, CD21), the receptor for both the C3d,g portion of human complement component C3 and the Epstein-Barr virus, has been recently described on peripheral T cells. By using dual stain flow cytometric analysis, we have also observed that a peripheral T lymphocyte subpopulation of normal healthy donors bears CR2 in a range varying from 1.1 to 23.2% (mean 12.6%) of total CD3+ cells. T lymphocytes from nine patients with inactive SLE expressed CR2 in a similar range. Three patients with active SLE were also studied. One of them, having neuropathy and glomerulonephritis, displayed an expansion of the CR2 T cell subpopulation which reached as much as 89% of total CD3+ cells. To examine potential functional roles of T cell CR2, cells from a Jurkat-derived CR2 expressing T cell line were found to bind in vitro to human CR2-, complement-coated K562 cell targets in a CR2- and complement-dependent fashion. Based on these studies, we hypothesize that CR2 might act to increase adherence of T cells to nucleated target cells bearing C3d,g, a function which may be relevant to cytotoxicity or other T cell activities requiring cell-cell interaction. PMID:1424280

  19. DNA immunization with plasmids expressing hCGbeta-chimeras.

    Science.gov (United States)

    Terrazzini, Nadia; Hannesdóttir, Sólveig; Delves, Peter J; Lund, Torben

    2004-06-01

    Human chorionic gonadotropin has been used as an anti-fertility vaccine and as a target for cancer immunotherapy. We have explored the use of DNA immunization with the aim of improving the immunogenicity of this hormone. Stimulating the muscle with electric pulses following intramuscular injection of plasmids expressing hCGbeta resulted in higher levels of human chorionic gonadotropin (hCG)-specific antibodies, which could be further enhanced following a protein boost with hCG mixed with adjuvant. DNA vaccines encoding a membrane attached or a secreted form of hCGbeta produced similar-albeit relatively modest-antibody responses. Providing hCGbeta with additional T cell help by vaccinating with a plasmid encoding a hCGbeta-hFc fusion protein did not further increase the antibody levels in the immunized animals. However, immunization of mice with a construct encoding hCGbeta fused to C3d(3) produced significantly lower antibody levels relative to mice immunized with the hCGbeta-alone expression plasmid, even though the hCGbeta-C3d(3) chimera was expected to facilitate cross-linking of the antigen-specific B-cell receptor and CR2 thereby lowering the threshold of activation. Thus the limiting factor determining the antibody levels following hCGbeta immunization, at least for DNA immunization, is related to the amount of protein available rather than the form of protein produced or lack of T cell epitopes. PMID:15149771

  20. Detachment of human immunodeficiency virus type 1 from germinal centers by blocking complement receptor type 2.

    Science.gov (United States)

    Kacani, L; Prodinger, W M; Sprinzl, G M; Schwendinger, M G; Spruth, M; Stoiber, H; Döpper, S; Steinhuber, S; Steindl, F; Dierich, M P

    2000-09-01

    After the transition from the acute to the chronic phase of human immunodeficiency virus (HIV) infection, complement mediates long-term storage of virions in germinal centers (GC) of lymphoid tissue. The contribution of particular complement receptors (CRs) to virus trapping in GC was studied on tonsillar specimens from HIV-infected individuals. CR2 (CD21) was identified as the main binding site for HIV in GC. Monoclonal antibodies (MAb) blocking the CR2-C3d interaction were shown to detach 62 to 77% of HIV type 1 from tonsillar cells of an individual in the presymptomatic stage. Although they did so at a lower efficiency, these antibodies were able to remove HIV from tonsillar cells of patients under highly active antiretroviral therapy, suggesting that the C3d-CR2 interaction remains a primary entrapment mechanism in treated patients as well. In contrast, removal of HIV was not observed with MAb blocking CR1 or CR3. Thus, targeting CR2 may facilitate new approaches toward a reduction of residual virus in GC. PMID:10933708

  1. 3D imaging with an isocentric mobile C-arm. Comparison of image quality with spiral CT

    Energy Technology Data Exchange (ETDEWEB)

    Kotsianos, Dorothea; Wirth, Stefan; Fischer, Tanja; Euler, Ekkehard; Rock, Clemens; Linsenmaier, Ulrich; Pfeifer, Klaus Juergen; Reiser, Maximilian [Departments of Radiology and Surgery, Klinikum der Universitaet Muenchen, Innenstadt, Nussbaumstrasse 20, 80336, Munchen (Germany)

    2004-09-01

    The purpose of this study was to evaluate the image quality of the new 3D imaging system (ISO-C-3D) for osteosyntheses of tibial condylar fractures in comparison with spiral CT (CT). Sixteen human cadaveric knees were examined with a C-arm 3D imaging system and spiral computed tomography. Various screws and plates of steel and titanium were used for osteosynthesis in these specimens. Image quality and clinical value of multiplanar (MP) reformatting of both methods were analyzed. In addition, five patients with tibial condylar fractures were examined for diagnosis and intra-operative control. The image quality of the C-arm 3D imaging system in the cadaveric study was rated as significantly worse than that of spiral CT with and without prostheses. After implantation of prostheses an increased incidence of artifacts was observed, but the diagnostic accuracy was not affected. Titanium implants caused the smallest number of artifacts. The image quality of ISO-C is inferior to CT, and metal artifacts were more prominent, but the clinical value was equal. ISO-C-3D can be useful in planning operative reconstructions and can verify the reconstruction of articular surfaces and the position of implants with diagnostic image quality. (orig.)

  2. Complement activation in Ghanaian children with severe Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Helegbe, Gideon K; Goka, Bamenla Q; Kurtzhals, Jørgen;

    2007-01-01

    leading to excess anaemia in acute P. falciparum infection. METHODS: The direct Coombs test (DCT) and flow cytometry were used to investigate the mean levels of RBC-bound complement fragments (C3d and C3balphabeta) and the regulatory proteins [complement receptor 1 (CD35) and decay accelerating factor (CD......55)] in children with discrete clinical forms of P. falciparum malaria. The relationship between the findings and clinical parameters including coma, haemoglobin (Hb) levels and RD were investigated. RESULTS: Of the 484 samples tested, 131(27%) were positive in DCT, out of which 115/131 (87.8%) were...... positive for C3d alone while 16/131 (12.2%) were positive for either IgG alone or both. 67.4% of the study population were below 5 years of age and DCT positivity was more common in this age group relative to children who were 5 years or older (Odds ratio, OR = 3.8; 95%CI, 2.2-6.7, p DCT...

  3. Anti-proliferative and ADMET screening of novel 3-(1H-indol-3-yl-1, 3-diphenylpropan-1-one derivatives

    Directory of Open Access Journals (Sweden)

    Manjunatha K. Siddappa

    2016-12-01

    Full Text Available Cancer tends to be one of the major diseases in the present century affecting global population, and proliferation of cancerous cells needs to be eliminated as the cell growth is uncontrolled. In this present study, a series of facile, high yielding 3-(1H-indol-3-yl-1, 3-diphenylpropan-1-ones 3(a–j was designed, synthesized and evaluated for anti-proliferative activity against different human cancer cell lines; MCF-7 (breast cancer, K562 (leukemic cancer, HeLa (cervical cancer, Colo205 (colorectal adreno carcinoma, HepG2 (Hepato cellular carcinoma cell lines. The compounds 3a, 3c, 3d, 3e, 3f, 3g and 3j exhibited an average inhibition of 35% against Hepatocellular Carcinoma (Hepg2 cell lines whereas, compounds 3a, 3c, 3d and 3e exhibited 33, 31, 35 and 33% inhibition, respectively, against HeLa cells at 10 μm concentrations. Doxorubicin was employed as a positive control. The ADME-TOX data was obtained by subjecting the molecules in silico to quantitatively predict the physicochemical properties. The structure of the title compounds were established by IR, 1H NMR, 13C NMR and Mass analysis.

  4. Assessment of in vivo complement activation on the Echinococcus granulosus hydatid cyst wall.

    Science.gov (United States)

    Ferreira, A M; Diaz, A; Fernandez, C; Sim, R B

    2001-12-01

    The larval stage of the parasite Echinococcus granulosus causes hydatid disease. The hydatid cyst is potentially capable of activating host complement, since it is a large, persistent, carbohydrate-rich structure, coated with host immunoglobulins, and localized in the host's internal organs. Nonetheless, in vitro studies have suggested that the cyst surface, the hydatid cyst wall (HCW), is a poor complement activator. In this study, we assessed the occurrence of in vivo complement activation on the hydatid cyst by measuring the levels of two complement activation products, C3d and complexes bearing a C9 activation neoepitope (TCC/MAC), in extracts from HCW of human origin. Low amounts of C3d and TCC/MAC were found in HCW in comparison with their levels in normal human plasma and activated human sera, suggesting that in vivo complement activation on HCW is efficiently down-regulated. This regulation may contribute to limit host inflammation which has been observed to correlate with parasite degeneration and death.

  5. A New Bio-Informatics Framework: Research on 3D Sensor Data of Human Activities

    Directory of Open Access Journals (Sweden)

    Sajid Ali

    2015-05-01

    Full Text Available Due to increasing attraction of motion capture systems technology and the usage of captured data in wide range of research-oriented applications, a framework has developed as an improved version of MOCAP TOOLBOX in Matlab platform. Firstly, we have introduced a faithful script to deal with public motion capture data, which will be friendly for us. Various functions through dynamic programming, by using the Body Segment Parameters (BSP are edited and they configured the position of markers according to data. It is used to visualize and refine without the MLS view and the C3D editor software. It has opened a valuable way of sensor data in many research aspects as gait movements, marker analysis, compression and motion pattern, bioinformatics, and animation. As a result, performed on CMU and ACCAD public mocap data, and achieved higher corrected configuration scheme of 3D markers when compared with the prior art, especially for C3D file. Another distinction of this work is that it handles the extra markers distortion, and provides the meaningful way to use captured data.

  6. Detachment of human immunodeficiency virus type 1 from germinal centers by blocking complement receptor type 2.

    Science.gov (United States)

    Kacani, L; Prodinger, W M; Sprinzl, G M; Schwendinger, M G; Spruth, M; Stoiber, H; Döpper, S; Steinhuber, S; Steindl, F; Dierich, M P

    2000-09-01

    After the transition from the acute to the chronic phase of human immunodeficiency virus (HIV) infection, complement mediates long-term storage of virions in germinal centers (GC) of lymphoid tissue. The contribution of particular complement receptors (CRs) to virus trapping in GC was studied on tonsillar specimens from HIV-infected individuals. CR2 (CD21) was identified as the main binding site for HIV in GC. Monoclonal antibodies (MAb) blocking the CR2-C3d interaction were shown to detach 62 to 77% of HIV type 1 from tonsillar cells of an individual in the presymptomatic stage. Although they did so at a lower efficiency, these antibodies were able to remove HIV from tonsillar cells of patients under highly active antiretroviral therapy, suggesting that the C3d-CR2 interaction remains a primary entrapment mechanism in treated patients as well. In contrast, removal of HIV was not observed with MAb blocking CR1 or CR3. Thus, targeting CR2 may facilitate new approaches toward a reduction of residual virus in GC.

  7. Executive Summary of Ares V: Lunar Capabilities Concept Review Through Phase A-Cycle 3

    Science.gov (United States)

    Holladay, J. B.; Baggett, K. E.; Feldman, S. M.

    2011-01-01

    This Technical Memorandum (TM) was generated as an overall Ares V summary from the Lunar Capabilities Concept Review (LCCR) through Phase A-Cycle 3 (PA-C3) with the intent that it may be coupled with separately published appendices for a more detailed, integrated narrative. The Ares V has evolved from the initial point of departure (POD) 51.00.48 LCCR configuration to the current candidate POD, PA-C3D, and the family of vehicles concept that contains vehicles PA-C3A through H. The logical progression from concept to POD vehicles is summarized in this TM and captures the trade space and performance of each. The family-of-vehicles concept was assessed during PA-C3 and offered flexibility in the path forward with the ability to add options deemed appropriate. A description of each trade space is given in addition to a summary of each Ares V element. The Ares V contributions to a Mars campaign are also highlighted with the goal of introducing Ares V capabilities within the trade space. The assessment of the Ares V vehicle as it pertains to Mars missions remained locked to the architecture presented in Mars Design Reference Authorization 5.0 using the PA-C3D vehicle configuration to assess Mars transfer vehicle options, in-space EDS capabilities, docking adaptor and propellant transfer assessments, and lunar and Mars synergistic potential.

  8. The Staphylococcus aureus protein Sbi acts as a complement inhibitor and forms a tripartite complex with host complement Factor H and C3b.

    Directory of Open Access Journals (Sweden)

    Katrin Haupt

    2008-12-01

    Full Text Available The Gram-positive bacterium Staphylococcus aureus, similar to other pathogens, binds human complement regulators Factor H and Factor H related protein 1 (FHR-1 from human serum. Here we identify the secreted protein Sbi (Staphylococcus aureus binder of IgG as a ligand that interacts with Factor H by a-to our knowledge-new type of interaction. Factor H binds to Sbi in combination with C3b or C3d, and forms tripartite SbiratioC3ratioFactor H complexes. Apparently, the type of C3 influences the stability of the complex; surface plasmon resonance studies revealed a higher stability of C3d complexed to Sbi, as compared to C3b or C3. As part of this tripartite complex, Factor H is functionally active and displays complement regulatory activity. Sbi, by recruiting Factor H and C3b, acts as a potent complement inhibitor, and inhibits alternative pathway-mediated lyses of rabbit erythrocytes by human serum and sera of other species. Thus, Sbi is a multifunctional bacterial protein, which binds host complement components Factor H and C3 as well as IgG and beta(2-glycoprotein I and interferes with innate immune recognition.

  9. Mechanism of quinine-dependent monoclonal antibody binding to platelet glycoprotein IIb/IIIa.

    Science.gov (United States)

    Bougie, Daniel W; Peterson, Julie; Rasmussen, Mark; Aster, Richard H

    2015-10-29

    Drug-dependent antibodies (DDAbs) that cause acute thrombocytopenia upon drug exposure are nonreactive in the absence of the drug but bind tightly to a platelet membrane glycoprotein, usually α(IIb)/β3 integrin (GPIIb/IIIa) when the drug is present. How a drug promotes binding of antibody to its target is unknown and is difficult to study with human DDAbs, which are poly-specific and in limited supply. We addressed this question using quinine-dependent murine monoclonal antibodies (mAbs), which, in vitro and in vivo, closely mimic antibodies that cause thrombocytopenia in patients sensitive to quinine. Using surface plasmon resonance (SPR) analysis, we found that quinine binds with very high affinity (K(D) ≈ 10⁻⁹ mol/L) to these mAbs at a molar ratio of ≈ 2:1 but does not bind detectably to an irrelevant mAb. Also using SPR analysis, GPIIb/IIIa was found to bind monovalently to immobilized mAb with low affinity in the absence of quinine and with fivefold greater affinity (K(D) ≈ 2.2 × 10⁻⁶) when quinine was present. Measurements of quinine-dependent binding of intact mAb and fragment antigen-binding (Fab) fragments to platelets showed that affinity is increased 10 000- to 100 000-fold by bivalent interaction between antibody and its target. Together, the findings indicate that the first step in drug-dependent binding of a DDAb is the interaction of the drug with antibody, rather than with antigen, as has been widely thought, where it induces structural changes that enhance the affinity/specificity of antibody for its target epitope. Bivalent binding may be essential for a DDAb to cause thrombocytopenia.

  10. Bispecificity for myelin and neuronal self-antigens is a common feature of CD4 T cells in C57BL/6 mice.

    Science.gov (United States)

    Lucca, Liliana E; Desbois, Sabine; Ramadan, Abdulraouf; Ben-Nun, Avraham; Eisenstein, Miriam; Carrié, Nadège; Guéry, Jean-Charles; Sette, Alessandro; Nguyen, Phuong; Geiger, Terrence L; Mars, Lennart T; Liblau, Roland S

    2014-10-01

    The recognition of multiple ligands by a single TCR is an intrinsic feature of T cell biology, with important consequences for physiological and pathological processes. Polyspecific T cells targeting distinct self-antigens have been identified in healthy individuals as well as in the context of autoimmunity. We have previously shown that the 2D2 TCR recognizes the myelin oligodendrocyte glycoprotein epitope (MOG)35-55 as well as an epitope within the axonal protein neurofilament medium (NF-M15-35) in H-2(b) mice. In this study, we assess whether this cross-reactivity is a common feature of the MOG35-55-specific T cell response. To this end, we analyzed the CD4 T cell response of MOG35-55-immunized C57BL/6 mice for cross-reactivity with NF-M15-35. Using Ag recall responses, we established that an important proportion of MOG35-55-specific CD4 T cells also responded to NF-M15-35 in all mice tested. To study the clonality of this response, we analyzed 22 MOG35-55-specific T cell hybridomas expressing distinct TCR. Seven hybridomas were found to cross-react with NF-M15-35. Using an alanine scan of NF-M18-30 and an in silico predictive model, we dissected the molecular basis of cross-reactivity between MOG35-55 and NF-M15-35. We established that NF-M F24, R26, and V27 proved important TCR contacts. Strikingly, the identified TCR contacts are conserved within MOG38-50. Our data indicate that due to linear sequence homology, part of the MOG35-55-specific T cell repertoire of all C57BL/6 mice also recognizes NF-M15-35, with potential implications for CNS autoimmunity. PMID:25135834

  11. Mixed-species associations in cuxiús (genus Chiropotes).

    Science.gov (United States)

    Shaffer, Christopher A; Barnett, Adrian A; Gregory, Tremaine; de Melo, Fabiano; Moreira, Leandro; Alvim, Thiago H G; Moura, Viviane S; Filó, Anderson; Cardoso, Tatiane; Port-Carvalho, Marcio; Santos, Ricardo Rodrigues dos; Boyle, Sarah A

    2016-05-01

    Polyspecific or mixed-species associations, where two or more species come together to forage and travel as a unit, have been reported in many primate species. These associations appear to offer a number of benefits to the species involved including increased foraging efficiency and decreased risk of predation. While several researchers have suggested that cuxiús (genus Chiropotes) form mixed-species associations, previous studies have not identified the circumstances under which cuxiús form associations or whether they form associations more often than would be expected by chance. Here we present data on the formation of mixed-species associations by four species of cuxiús at eight different sites in Brazil, Suriname, and Guyana. We analyzed data from two of the study sites, (Biological Dynamics of Forest Fragments Project (BDFFP), Brazil and the Upper Essequibo Conservation Concession (UECC), Guyana, to assess whether associations occurred more than would be expected by chance encounters and identify the factors influencing their formation. Cuxiús showed a high degree of inter-site variation in the frequency of time spent in association (ranging from 2 to 26% of observation time) and duration of associations (mean duration from 22 min to 2.5 hr). Sapajus apella was the most common association partner at most sites. At BDFFP, cuxiús formed associations more frequently but not for longer duration than expected by chance. For much of the year at UECC, associations were not more frequent or longer than chance. However, during the dry season, cuxiús formed associations with S. apella significantly more often and for longer duration than predicted by chance. Cuxiús at UECC formed associations significantly more often when in smaller subgroups and when foraging for insects, and alarm called significantly less frequently during associations. We suggest cuxiús form mixed-species associations at some sites as an adaptive strategy to decrease predation risk and

  12. Detection of virus-specific intrathecally synthesised immunoglobulin G with a fully automated enzyme immunoassay system

    Directory of Open Access Journals (Sweden)

    Weissbrich Benedikt

    2007-05-01

    Full Text Available Abstract Background The determination of virus-specific immunoglobulin G (IgG antibodies in cerebrospinal fluid (CSF is useful for the diagnosis of virus associated diseases of the central nervous system (CNS and for the detection of a polyspecific intrathecal immune response in patients with multiple sclerosis. Quantification of virus-specific IgG in the CSF is frequently performed by calculation of a virus-specific antibody index (AI. Determination of the AI is a demanding and labour-intensive technique and therefore automation is desirable. We evaluated the precision and the diagnostic value of a fully automated enzyme immunoassay for the detection of virus-specific IgG in serum and CSF using the analyser BEP2000 (Dade Behring. Methods The AI for measles, rubella, varicella-zoster, and herpes simplex virus IgG was determined from pairs of serum and CSF samples of patients with viral CNS infections, multiple sclerosis and of control patients. CSF and serum samples were tested simultaneously with reference to a standard curve. Starting dilutions were 1:6 and 1:36 for CSF and 1:1386 and 1:8316 for serum samples. Results The interassay coefficient of variation was below 10% for all parameters tested. There was good agreement between AIs obtained with the BEP2000 and AIs derived from the semi-automated reference method. Conclusion Determination of virus-specific IgG in serum-CSF-pairs for calculation of AI has been successfully automated on the BEP2000. Current limitations of the assay layout imposed by the analyser software should be solved in future versions to offer more convenience in comparison to manual or semi-automated methods.

  13. Maternal anti-M induced hemolytic disease of newborn followed by prolonged anemia in newborn twins

    Directory of Open Access Journals (Sweden)

    Satyam Arora

    2015-01-01

    Full Text Available Allo-anti-M often has an immunoglobulin G (IgG component but is rarely clinically significant. We report a case of hemolytic disease of the fetus and newborn along with prolonged anemia in newborn twins that persisted for up to 70 days postbirth. The aim was to diagnose and successfully manage hemolytic disease of newborn (HDN due to maternal alloimmunization. Direct antiglobulin test (DAT, antigen typing, irregular antibody screening and identification were done by polyspecific antihuman globulin cards and standard tube method. At presentation, the newborn twins (T1, T2 had HDN with resultant low reticulocyte count and prolonged anemia, which continued for up to 70 days of life. Blood group of the twins and the mother was O RhD positive. DAT of the both newborns at birth was negative. Anti-M was detected in mothers as well as newborns. Type of antibody in mother was IgG and IgM type whereas in twins it was IgG type only. M antigen negative blood was transfused thrice to twin-1 and twice to twin-2. Recurring reduction of the hematocrit along with low reticulocyte count and normal other cell line indicated a pure red cell aplastic state. Anti-M is capable of causing HDN as well as prolonged anemia (red cell aplasia due to its ability to destroy the erythroid precursor cells. Newborns with anemia should be evaluated for all the possible causes to establish a diagnosis and its efficient management. Mother should be closely monitored for future pregnancies as well.

  14. Rationally evolving tRNAPyl for efficient incorporation of noncanonical amino acids.

    Science.gov (United States)

    Fan, Chenguang; Xiong, Hai; Reynolds, Noah M; Söll, Dieter

    2015-12-15

    Genetic encoding of noncanonical amino acids (ncAAs) into proteins is a powerful approach to study protein functions. Pyrrolysyl-tRNA synthetase (PylRS), a polyspecific aminoacyl-tRNA synthetase in wide use, has facilitated incorporation of a large number of different ncAAs into proteins to date. To make this process more efficient, we rationally evolved tRNA(Pyl) to create tRNA(Pyl-opt) with six nucleotide changes. This improved tRNA was tested as substrate for wild-type PylRS as well as three characterized PylRS variants (N(ϵ)-acetyllysyl-tRNA synthetase [AcKRS], 3-iodo-phenylalanyl-tRNA synthetase [IFRS], a broad specific PylRS variant [PylRS-AA]) to incorporate ncAAs at UAG codons in super-folder green fluorescence protein (sfGFP). tRNA(Pyl-opt) facilitated a 5-fold increase in AcK incorporation into two positions of sfGFP simultaneously. In addition, AcK incorporation into two target proteins (Escherichia coli malate dehydrogenase and human histone H3) caused homogenous acetylation at multiple lysine residues in high yield. Using tRNA(Pyl-opt) with PylRS and various PylRS variants facilitated efficient incorporation of six other ncAAs into sfGFP. Kinetic analyses revealed that the mutations in tRNA(Pyl-opt) had no significant effect on the catalytic efficiency and substrate binding of PylRS enzymes. Thus tRNA(Pyl-opt) should be an excellent replacement of wild-type tRNA(Pyl) for future ncAA incorporation by PylRS enzymes.

  15. Structure-Based Reverse Vaccinology Failed in the Case of HIV Because it Disregarded Accepted Immunological Theory

    Science.gov (United States)

    Van Regenmortel, Marc H. V.

    2016-01-01

    Two types of reverse vaccinology (RV) should be distinguished: genome-based RV for bacterial vaccines and structure-based RV for viral vaccines. Structure-based RV consists in trying to generate a vaccine by first determining the crystallographic structure of a complex between a viral epitope and a neutralizing monoclonal antibody (nMab) and then reconstructing the epitope by reverse molecular engineering outside the context of the native viral protein. It is based on the unwarranted assumption that the epitope designed to fit the nMab will have acquired the immunogenic capacity to elicit a polyclonal antibody response with the same protective capacity as the nMab. After more than a decade of intensive research using this type of RV, this approach has failed to deliver an effective, preventive HIV-1 vaccine. The structure and dynamics of different types of HIV-1 epitopes and of paratopes are described. The rational design of an anti-HIV-1 vaccine is shown to be a misnomer since investigators who claim that they design a vaccine are actually only improving the antigenic binding capacity of one epitope with respect to only one paratope and not the immunogenic capacity of an epitope to elicit neutralizing antibodies. Because of the degeneracy of the immune system and the polyspecificity of antibodies, each epitope studied by the structure-based RV procedure is only one of the many epitopes that the particular nMab is able to recognize and there is no reason to assume that this nMab must have been elicited by this one epitope of known structure. Recent evidence is presented that the trimeric Env spikes of the virus possess such an enormous plasticity and intrinsic structural flexibility that it is it extremely difficult to determine which Env regions are the best candidate vaccine immunogens most likely to elicit protective antibodies. PMID:27657055

  16. Why Does the Molecular Structure of Broadly Neutralizing Monoclonal Antibodies Isolated from Individuals Infected with HIV-1 not Inform the Rational Design of an HIV-1 Vaccine?

    Directory of Open Access Journals (Sweden)

    Marc H V Van Regenmortel

    2015-05-01

    Full Text Available It is commonly assumed that neutralizing Mabs that bind to the HIV-1 Env glycoprotein are more specific reagents than anti-HIV-1 polyclonal antisera and that knowledge of the structure of these Mabs facilitates the rational design of effective HIV-1 vaccine immunogens. However, after more than ten years of unsuccessful experimentation using the structure-based reverse vaccinology approach, it is now evident that it is not possible to infer from the structure of neutralizing Mabs which HIV immunogens induced their formation nor which vaccine immunogens will elicit similar Abs in an immunized host. The use of Mabs for developing an HIV-1 vaccine was counterproductive because it overlooked the fact that the apparent specificity of a Mab very much depends on the selection procedure used to obtain it and also did not take into account that an antibody is never monospecific for a single epitope but is always polyspecific for many epitopes. When the rationale of the proponents of the unsuccessful rational design strategy is analyzed, it appears that investigators who claim they are designing a vaccine immunogen are only improving the binding reactivity of a single epitope-paratope pair and are not actually designing an immunogen able to generate protective antibodies. The task of a designer consists in imagining what type of immunogen is likely to elicit a protective immune response but in the absence of knowledge regarding which features of the immune system are responsible for producing a functional neutralizing activity in antibodies, it is not feasible to intentionally optimize a potential immunogen candidate in order to obtain the desired outcome. The only available option is actually to test possible solutions by trial-and-error experiments until the preset goal is perhaps attained. Rational design and empirical approaches in HIV vaccine research should thus not be opposed as alternative options since empirical testing is an integral part of a so

  17. Basic Research in HIV vaccinology is hampered by reductionist thinking

    Directory of Open Access Journals (Sweden)

    Marc H V Van Regenmortel

    2012-07-01

    Full Text Available This review describes the structure-based reverse vaccinology approach aimed at developing vaccine immunogens capable of inducing antibodies that broadly neutralize HIV-1. Some basic principles of protein immunochemistry are reviewed and the implications of the extensive polyspecificity of antibodies for vaccine development are underlined. Although it is natural for investigators to want to know the cause of an effective immunological intervention, the classic notion of causality is shown to have little explanatory value for a system as complex as the immune system, where any observed effect always results from many interactions between a large number of components. Causal explanations are reductive because a single factor is singled out for attention and given undue explanatory weight on its own. Other examples of the negative impact of reductionist thinking on HIV vaccine development are discussed. These include 1 the failure to distinguish between the chemical nature of antigenicity and the biological nature of immunogenicity, 2 the belief that when an HIV-1 epitope is reconstructed by rational design to better fit a neutralizing Mab, this will produce an immunogen able to elicit Abs with the same neutralizing capacity as the Ab used as template for designing the antigen 3 the belief that protection against infection can be analysed at the level of individual molecular interactions although it has meaning only at the level of an entire organism.The numerous unsuccessful strategies that have been used to design HIV-1 vaccine immunogens are described and it is suggested that the convergence of so many negative experimental results, justifies the conclusion that reverse vaccinology is unlikely to lead to the development of a preventive HIV-1 vaccine. Immune correlates of protection in vaccinees have not yet been identified because this will become feasible only retrospectively once an effective vaccine exists.

  18. An outdated notion of antibody specificity is one of the major detrimental assumptions of the structure-based reverse vaccinology paradigm which prevented it from helping to develop an effective HIV-1 vaccine

    Directory of Open Access Journals (Sweden)

    Marc H V Van Regenmortel

    2014-11-01

    Full Text Available The importance of paradigms for guiding scientific research is explained with reference to the seminal work of Karl Popper and Thomas Kuhn. A prevalent paradigm, followed for more than a decade in HIV-1 vaccine research, which gave rise to the strategy known as structure-based reverse vaccinology is described in detail. Several reasons why this paradigm did not allow the development of an effective HIV-1 vaccine are analyzed. A major reason is the belief shared by many vaccinologists that antibodies possess a narrow specificity for a single epitope and are not polyspecific for a diverse group of potential epitopes. When this belief is abandoned, it becomes obvious that the one particular epitope structure observed during the crystallographic analysis of a neutralizing antibody-antigen complex does not necessarily reveal which immunogenic structure should be used to elicit the same type of neutralizing antibody.In the physical sciences, scientific explanations are usually presented as logical deductions derived from a relevant law of nature together with certain initial conditions. In immunology, causal explanations in terms of a single cause acting according to a law of nature are not possible because numerous factors always play a role in bringing about an effect. The implications of this state of affairs for the rational design of HIV vaccines are outlined. An alternative approach to obtain useful scientific understanding consists in intervening empirically in the immune system and it is suggested that manipulating the system experimentally is needed to learn to control it and achieve protective immunity by vaccination.

  19. ADMET Evaluation in Drug Discovery. 16. Predicting hERG Blockers by Combining Multiple Pharmacophores and Machine Learning Approaches.

    Science.gov (United States)

    Wang, Shuangquan; Sun, Huiyong; Liu, Hui; Li, Dan; Li, Youyong; Hou, Tingjun

    2016-08-01

    Blockade of human ether-à-go-go related gene (hERG) channel by compounds may lead to drug-induced QT prolongation, arrhythmia, and Torsades de Pointes (TdP), and therefore reliable prediction of hERG liability in the early stages of drug design is quite important to reduce the risk of cardiotoxicity-related attritions in the later development stages. In this study, pharmacophore modeling and machine learning approaches were combined to construct classification models to distinguish hERG active from inactive compounds based on a diverse data set. First, an optimal ensemble of pharmacophore hypotheses that had good capability to differentiate hERG active from inactive compounds was identified by the recursive partitioning (RP) approach. Then, the naive Bayesian classification (NBC) and support vector machine (SVM) approaches were employed to construct classification models by integrating multiple important pharmacophore hypotheses. The integrated classification models showed improved predictive capability over any single pharmacophore hypothesis, suggesting that the broad binding polyspecificity of hERG can only be well characterized by multiple pharmacophores. The best SVM model achieved the prediction accuracies of 84.7% for the training set and 82.1% for the external test set. Notably, the accuracies for the hERG blockers and nonblockers in the test set reached 83.6% and 78.2%, respectively. Analysis of significant pharmacophores helps to understand the multimechanisms of action of hERG blockers. We believe that the combination of pharmacophore modeling and SVM is a powerful strategy to develop reliable theoretical models for the prediction of potential hERG liability. PMID:27379394

  20. Progress in Study on Organic Anion Transporters%有机阴离子转运蛋白的研究进展

    Institute of Scientific and Technical Information of China (English)

    宋必卫; 周彦君

    2012-01-01

    有机阴离子转运蛋白(organic anion transporters,OATs)是一类底物特异性较差、主要表达于屏障上皮的转运蛋白,主要位于肾近曲小管,在其他器官如肝、脑和胎盘也有分布,介导众多带负电的体内代谢产物(包括尿酸、神经递质酸性代谢终产物、甾体激素、前列腺素等)和药物跨细胞转运,对药物排泄和药动学有重要影响.本文就已克隆的各亚型OATs的特性、生理功能及其活性调节、转运机制、底物、对药动力学的影响等方面作一介绍.%Organic anion transporters (OATs) belong to a family of poly-specific transporters mainly located in barrier epithelia such as renal proximal tubule, brain, liver and placenta. OATs interact with endogenous metabolic end products such as urate and acidic neutrotransmitter metabolites, as well as with a multitude of widely used drugs, including antibiotics, diuretics, antihypertensives and anti-inflammatory drugs. Thereby, OATs play an important role in renal drug elimination and have an impact on pharma-cokinetics. This review summarizes current knowledge of the properties and functional roles of the cloned OAT family members detailed in tissue differences in expression and physiologic function, drug-drug interactions, and finally, gender-dependent regulation in health and diseased states.

  1. Identification and characterization of a bacterial hydrosulphide ion channel

    Energy Technology Data Exchange (ETDEWEB)

    Czyzewski, Bryan K.; Wang, Da-Neng (NYUSM)

    2012-10-26

    The hydrosulphide ion (HS{sup -}) and its undissociated form, hydrogen sulphide (H{sub 2}S), which are believed to have been critical to the origin of life on Earth, remain important in physiology and cellular signalling. As a major metabolite in anaerobic bacterial growth, hydrogen sulphide is a product of both assimilatory and dissimilatory sulphate reduction. These pathways can reduce various oxidized sulphur compounds including sulphate, sulphite and thiosulphate. The dissimilatory sulphate reduction pathway uses this molecule as the terminal electron acceptor for anaerobic respiration, in which process it produces excess amounts of H{sub 2}S. The reduction of sulphite is a key intermediate step in all sulphate reduction pathways. In Clostridium and Salmonella, an inducible sulphite reductase is directly linked to the regeneration of NAD{sup +}, which has been suggested to have a role in energy production and growth, as well as in the detoxification of sulphite. Above a certain concentration threshold, both H{sub 2}S and HS{sup -} inhibit cell growth by binding the metal centres of enzymes and cytochrome oxidase, necessitating a release mechanism for the export of this toxic metabolite from the cell. Here we report the identification of a hydrosulphide ion channel in the pathogen Clostridium difficile through a combination of genetic, biochemical and functional approaches. The HS{sup -} channel is a member of the formate/nitrite transport family, in which about 50 hydrosulphide ion channels form a third subfamily alongside those for formate (FocA) and for nitrite (NirC). The hydrosulphide ion channel is permeable to formate and nitrite as well as to HS{sup -} ions. Such polyspecificity can be explained by the conserved ion selectivity filter observed in the channel's crystal structure. The channel has a low open probability and is tightly regulated, to avoid decoupling of the membrane proton gradient.

  2. First clinical experiences with a new ovine Fab Echis ocellatus snake bite antivenom in Nigeria: randomized comparative trial with Institute Pasteur Serum (Ipser) Africa antivenom.

    Science.gov (United States)

    Meyer, W P; Habib, A G; Onayade, A A; Yakubu, A; Smith, D C; Nasidi, A; Daudu, I J; Warrell, D A; Theakston, R D

    1997-03-01

    During the past decade, effective snake antivenoms have become scarce in northern Nigeria. As a result, many patients severely envenomed by the saw-scaled or carpet viper (Echis ocellatus), which is responsible for more than 95% of the snake bites in the region, did not receive effective treatment and mortality and morbidity increased. To combat this crisis, a new monospecific ovine Fab antivenom (EchiTab) is being developed. Its theoretical advantages over conventional equine F(ab')2 antivenom are a more rapid tissue penetration and larger apparent volume of distribution (the volume of [tissue] fluid in which the the antivenom would be uniformly distributed to achieve the observed plasma concentration). In a preliminary study, two vials (20 ml; 1.0 g of protein) of EchiTab rapidly and permanently restored blood coagulability and cleared venom antigenemia in seven envenomed patients. Four experienced early reactions that responded to epinephrine. In a randomized comparative trial of one vial (10 ml; 0.5 g protein) of EchiTab or four ampules (40 ml; 2.12 g of protein) of Institute Pasteur Serum (Ipser) Africa polyspecific F(ab')2 antivenom, there were fewer reactions, but only 36% and 35% of patients, respectively, showed permanent restoration of coagulability, with the remainder requiring further doses. This suggests that 0.5 g (one vial) of EchiTab is approximately equivalent to 2.12 g (four ampules) of Ipser Africa antivenom, and that a higher initial dose will be required for most patients. Measurements of circulating venom and antivenom levels reflected the clinical events. PMID:9129531

  3. A season of snakebite envenomation: presentation patterns, timing of care, anti-venom use, and case fatality rates from a hospital of southcentral Nepal.

    Science.gov (United States)

    Pandey, Deb P; Vohra, Rais; Stalcup, Philip; Shrestha, Bhola R

    2016-01-01

    Snakebite envenomation affects thousands of people annually in Nepal. Published hospital-based studies of snakebite treatment in Nepal are scarce. Here we present the results of the first prospective, cross-sectional study of hospitalized envenomed snakebite cases in southcentral Nepal, a region characterized by poor pre-hospital care of snakebites, limited supply and excessive use of antivenom, and a high case/fatality ratio. We seek to identify clinical management problems and suggest potential interventions to improve treatment of snakebites. Out of the 342 patients presented with snakebites to an urban emergency department in the Terai region of Nepal between April and September of 2007, 39 patients were enrolled based on development of ptosis or swelling of bitten body parts. We collected patient demographic information and documented circumstances of snakebite, prehospital care, hospital care, and development of complications. Among 39 envenomated patients admitted to Bharatpur Hospital enrolled in the study 34 (92%) exhibited features of clinically significant neurotoxicity and were treated with antivenom. Antivenom use ranged from 4 to 98 vials of Polyspecific Indian Antivenom per patient. Each of victims (n=34) received antivenom an average of 4.3 (median) ±0.73 (standard error of mean) hours after receiving the snakebite. The overall case fatality rate was 21%. Neurotoxicity developed up to 25.8hr after suspected elapid snakebites. This was not observed for viperid snake bites. No enrolled patients received any of the currently recommended first aid for snake bite. The prevalence of nocturnal elapid snake bites, the practice of inappropriate first aid measures and highly variable administration of antivenom were identified as major challenges to appropriate care in this study. To address these issues we suggest development of a comprehensive checklist for identification of snake species, management of envenomation, and an educational program which

  4. ADMET Evaluation in Drug Discovery. 16. Predicting hERG Blockers by Combining Multiple Pharmacophores and Machine Learning Approaches.

    Science.gov (United States)

    Wang, Shuangquan; Sun, Huiyong; Liu, Hui; Li, Dan; Li, Youyong; Hou, Tingjun

    2016-08-01

    Blockade of human ether-à-go-go related gene (hERG) channel by compounds may lead to drug-induced QT prolongation, arrhythmia, and Torsades de Pointes (TdP), and therefore reliable prediction of hERG liability in the early stages of drug design is quite important to reduce the risk of cardiotoxicity-related attritions in the later development stages. In this study, pharmacophore modeling and machine learning approaches were combined to construct classification models to distinguish hERG active from inactive compounds based on a diverse data set. First, an optimal ensemble of pharmacophore hypotheses that had good capability to differentiate hERG active from inactive compounds was identified by the recursive partitioning (RP) approach. Then, the naive Bayesian classification (NBC) and support vector machine (SVM) approaches were employed to construct classification models by integrating multiple important pharmacophore hypotheses. The integrated classification models showed improved predictive capability over any single pharmacophore hypothesis, suggesting that the broad binding polyspecificity of hERG can only be well characterized by multiple pharmacophores. The best SVM model achieved the prediction accuracies of 84.7% for the training set and 82.1% for the external test set. Notably, the accuracies for the hERG blockers and nonblockers in the test set reached 83.6% and 78.2%, respectively. Analysis of significant pharmacophores helps to understand the multimechanisms of action of hERG blockers. We believe that the combination of pharmacophore modeling and SVM is a powerful strategy to develop reliable theoretical models for the prediction of potential hERG liability.

  5. Heterophile antibody interference in a solid phase sandwich immunoassay for detection of equine growth hormone in plasma.

    Science.gov (United States)

    Borromeo, V; Berrini, A; Gaggioli, D; Secchi, C

    2007-01-15

    Heterophile antibodies (HAs) present in serum recognize animal immunoglobulins and are one of the most unpredictable causes of false results in immunoassays. However, no study has yet reported their interference on the diagnostic reliability of immunochemical analyses on horse plasma. Recently, we developed a sandwich ELISA for detection of equine growth hormone (eGH) in plasma. In a pilot study to measure basal eGH levels (blood samples were drawn from 13 horses every 10 min for 1h), we noted one horse with abnormally high eGH (>100 ng/mL). We demonstrate here that this plasma eGH level was falsely elevated due to interference from HAs. The interfering antibodies were polyspecific immunoglobulins, with fairly broad species-specificity, which affected the eGH immunoassay by bridging the mouse IgG capture antibody and the rabbit IgG conjugate. This produced artificial sandwiches which led to overestimation of the eGH plasma concentration. Spiking horse plasma with pure mouse and rabbit immunoglobulins or whole plasma of several species significantly reduced but did not totally eliminate the HAs interference. Immunoglobulins and whole plasma differed in their ability to block the interference, suggesting that HAs may recognize other proteins beside immunoglobulins in animal sera. To investigate whether HAs have any implications in equine clinical practice, we decided to seek information on the incidence of HAs interference in normal animals. We collected single plasma samples from another 114 horses and we found that 5 of these had plasma HAs. Therefore, in total 6 out of the 127 horses examined (4.7%) had plasma HAs generating falsely elevated eGH measures. In conclusion, this study provides the first evidence of HAs in horse plasma interfering with an immunoassay and indicates that veterinary surgeons and diagnostic laboratory staff should be aware of this potential for interference in tests on horse plasma using monoclonal or polyclonal antibody reagents. PMID

  6. Rationally evolving tRNAPyl for efficient incorporation of noncanonical amino acids

    Science.gov (United States)

    Fan, Chenguang; Xiong, Hai; Reynolds, Noah M.; Söll, Dieter

    2015-01-01

    Genetic encoding of noncanonical amino acids (ncAAs) into proteins is a powerful approach to study protein functions. Pyrrolysyl-tRNA synthetase (PylRS), a polyspecific aminoacyl-tRNA synthetase in wide use, has facilitated incorporation of a large number of different ncAAs into proteins to date. To make this process more efficient, we rationally evolved tRNAPyl to create tRNAPyl-opt with six nucleotide changes. This improved tRNA was tested as substrate for wild-type PylRS as well as three characterized PylRS variants (Nϵ-acetyllysyl-tRNA synthetase [AcKRS], 3-iodo-phenylalanyl-tRNA synthetase [IFRS], a broad specific PylRS variant [PylRS-AA]) to incorporate ncAAs at UAG codons in super-folder green fluorescence protein (sfGFP). tRNAPyl-opt facilitated a 5-fold increase in AcK incorporation into two positions of sfGFP simultaneously. In addition, AcK incorporation into two target proteins (Escherichia coli malate dehydrogenase and human histone H3) caused homogenous acetylation at multiple lysine residues in high yield. Using tRNAPyl-opt with PylRS and various PylRS variants facilitated efficient incorporation of six other ncAAs into sfGFP. Kinetic analyses revealed that the mutations in tRNAPyl-opt had no significant effect on the catalytic efficiency and substrate binding of PylRS enzymes. Thus tRNAPyl-opt should be an excellent replacement of wild-type tRNAPyl for future ncAA incorporation by PylRS enzymes. PMID:26250114

  7. Thermal-structural coupling analysis of disk brake%盘式制动器热结构耦合分析

    Institute of Scientific and Technical Information of China (English)

    朱永梅; 朱玉君; 王新国; 张奔

    2015-01-01

    The article expresses the direct thermal-structural coupling of disk brake by Abaqus .The C3D8T ele-ment has the degrees of freedom to calculate the temperature and structure , so we mesh the 3-dimensional disk brake model with the C3D8T element and analyze the initial conditions , boundary conditions and loads on the fi-nite element model .The selection and calculation of friction coefficient , function of heat flux and convection heat transfer coefficient are discussed in detail .The temperature contours are analized and the effects of different structural and material parameters of the brake disc are compared .The analysis provides a reliable basis for choosing the disc material , designing structural size , selecting braking conditions , and preventing brake disc fail-ure .%文中应用ABAQUS软件对盘式制动器进行热结构直接耦合分析,采用具有温度计算和结构计算所需自由度的C3 D8 T单元,对制动盘三维模型划分网格;分析了有限元模型的初始条件、边界条件和载荷施加,详细讨论了制动件之间摩擦系数、热流密度函数和对流散热系数的选取和计算;分析了制动盘制动模拟过程中的温度云图,比较制动盘的不同结构和材料参数对制动盘表面温升的影响。分析结果对制动盘材料选择、结构尺寸设计、制动工况选择、制动盘破坏预防等工作提供了可靠依据。

  8. CD21/CR2的研究进展

    Institute of Scientific and Technical Information of China (English)

    王琳

    2003-01-01

    补体Ⅱ型受体CD21/CR2是B淋巴细胞膜表面C3d/iC3b受体,在免疫应答中起重要的作用。同时人CD21/CR2也是EB病毒膜表面糖蛋白gp350/gp220、HIV-1等的受体,CD21/CR2以不同的结构域与这些配体结合,表现出多种生物学特性。弄清CD21/CR2的结构和功能,可以指导基础免疫研究,也可明确临床许多疾病的发病机理和治疗方向。

  9. Assessment of left heart and pulmonary circulation flow dynamics by a new pulsed mock circulatory system

    Science.gov (United States)

    Tanné, David; Bertrand, Eric; Kadem, Lyes; Pibarot, Philippe; Rieu, Régis

    2010-05-01

    We developed a new mock circulatory system that is able to accurately simulate the human blood circulation from the pulmonary valve to the peripheral systemic capillaries. Two independent hydraulic activations are used to activate an anatomical-shaped left atrial and a left ventricular silicon molds. Using a lumped model, we deduced the optimal voltage signals to control the pumps. We used harmonic analysis to validate the experimental pulmonary and systemic circulation models. Because realistic volumes are generated for the cavities and the resulting pressures were also coherent, the left atrium and left ventricle pressure-volume loops were concordant with those obtained in vivo. Finally we explored left atrium flow pattern using 2C-3D+T PIV measurements. This gave a first overview of the complex 3D flow dynamics inside realistic left atrium geometry.

  10. THE KFIB EXPERIMENT

    Energy Technology Data Exchange (ETDEWEB)

    Youngblood, Gerald E.; Senor, David J.; Jones, Russell H.; Kowbel, W.; Kohyama, A.

    2000-06-30

    Several rod-shaped specimens with uniaxially packed fibers (Hi-Nicalon™, Hi-Nicalon™ Type S, Tyranno™ SA and Amoco K1100™ types) in a pre-ceramic polymer matrix were fabricated. By using appropriate analytic models, the bare fiber thermal conductivity (Kf) will be determined as a function of temperature up to 1000°C before and after irradiation for samples cut from these rods. Preliminary thermal conductivity data for unirradiated fibers (Hi-Nicalon™ and Tyranno™ SA-B SiC and K1100™ graphite) and for three types of unirradiated composites made from these fibers (2D-Nicalon S/SiC multilayer/CVI-SiC, 3D-Nicalon S/PIP-SiC, and 2D-8HS Tyrannohex™ HP) are presented.

  11. Study on the Extraction Technology of Flavonoid Compounds from Tribulus Terrestris%正交设计优选刺疾藜总黄酮的提取工艺

    Institute of Scientific and Technical Information of China (English)

    李君玲; 王大伟

    2008-01-01

    目的:研究刺蒺藜中总黄酮的提取工艺.方法:以浸膏得率和总黄酮含量为考察指标.采用正交试验法,考察加醇量、提取次数、提取时间、乙醇浓度4个因素对提取工艺的影响.结果:最佳提取工艺为A1B3C3D2,即药材加乙醇10倍量,提取3次,提取时间3h,乙醇浓度80%.结论:正交试验法优选刺蒺藜总黄酮的提取工艺简便、快速、准确.

  12. Design and synthesis of novel triazole antifungal derivatives based on the active site of fungal lanosterol 14a-demethylase (CYP51)

    Institute of Scientific and Technical Information of China (English)

    Zhi Gang Dan; Jun Zhang; Shi Chong Yu; Hong Gang Hu; Xiao Yun Chai; Qing Yan Sun; Qiu Ye Wu

    2009-01-01

    A series of 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-(N-isoproyl-N-substituted-amino)-2-propanols have been designed and synthesized on the basis of the active site of lanosterol 14a-demethylase (CYP51). Their structures were confirmed by MS and 1H NMR. In vitro antifungal activities of these synthesized compounds were evaluated against eight human pathogenic fungi. The results showed that all title compounds exhibited activity against fungi tested to some extent. Compounds 3c, 3d, 7a, 7b and 7c exhibited more potent antifungal activities against nearly all fungi tested except Aspergillus fumigatus than fluconazole.

  13. Underground earth strain and seismic radiation measurements with a laser interferometer and a dense small-aperture seismic array

    Directory of Open Access Journals (Sweden)

    M. Abril

    1997-06-01

    Full Text Available This paper describes two geophysical instruments, installed in the underground physics laboratories of Gran Sasso (LNGS-INFN, located in the seismic zone of the Central Apennines, Italy. These instruments monitor strain and seismic radiation with very high sensitivity: one is a 90 m-long laser interferometer, sensitivity 3 x 10-12, frequency response 10-7-10-2 Hz, and has been operating since 1994. The other is a small-aperture seismic array composed of 21 three-component short period (Mark L4C-3D and 3 broadband (Guralp CMG-3ESP seismometers. This dense array will be in operation at the beginning of 1998.

  14. Synthesis and biological activity of novel tiliroside derivants.

    Science.gov (United States)

    Qin, Nan; Li, Chun-Bao; Jin, Mei-Na; Shi, Li-Huan; Duan, Hong-Quan; Niu, Wen-Yan

    2011-10-01

    A series of new tiliroside derivatives were synthesized and characterized by analytical (1)H NMR, (13)C NMR and mass spectrometry. All of the compounds were evaluated for anti-diabetic properties in vitro using HepG2 cells. Compounds 3c, 3d, and 3i-l caused significant enhancements in glucose consumption by insulin-resistant HepG2 cells compared with control cells and cells that were exposed to metformin (an anti-diabetic drug). Moreover, compound 3l significantly activated adenosine 5'-monophosphate-activated protein kinase activity and reduced acetyl-CoA carboxylase activity. Thus, the tiliroside derivative 3l offers potential to be developed as a new approach for treating type II diabetes.

  15. Influence of resonances on spectral formation of x-ray lines in Fe XVII.

    Science.gov (United States)

    Chen, Guo Xin; Pradhan, Anil K

    2002-07-01

    New theoretical results from large-scale relativistic close coupling calculations reveal the precise effect of resonances in collisional excitation of x-ray lines of Ne-like Fe XVII. By employing the Breit-Pauli R-matrix method and an 89-level eigenfunction expansion, including up to n = 4 levels, significant resonance enhancement of the collision strengths of forbidden and intercombination transitions is shown. The present results should help resolve long-standing discrepancies; in particular, the present line ratios of three benchmark diagnostic lines 3C, 3D, and 3E at 15.014, 15.265, and 15.456 A, respectively, are in excellent agreement with two independent measurements on electron-beam ion traps. Strong energy dependence in cross sections due to resonances is demonstrated. PMID:12097041

  16. Structural basis for simvastatin competitive antagonism of complement receptor 3

    DEFF Research Database (Denmark)

    Jensen, Maria Risager; Bajic, Goran; Zhang, Xianwei;

    2016-01-01

    The complement system is an important part of the innate immune response to infection, but may also cause severe complications during inflammation. Small molecule antagonists to complement receptor (CR)3 have been widely sought, but a structural basis for their mode of action is not available. We...... report here on the structure of the human CR3 ligand-binding I domain in complex with simvastatin. Simvastatin targets the metal ion-dependent adhesion site of the open, ligand-binding conformation of the CR3 I domain by direct contact with the chelated Mg2+ ion. Simvastatin antagonizes I domain binding...... to the complement fragments iC3b and C3d, but not to intercellular adhesion molecule-1. By virtue of the I domain's wide distribution in binding kinetics to ligands, it was possible to identify ligand binding kinetics as discriminator for simvastatin antagonism. In static cellular experiments, 15-25 μM simvastatin...

  17. Complement binding to erythrocytes is associated with macrophage activation and reduced haemoglobin in Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Goka, B Q; Kwarko, H; Kurtzhals, J A;

    2001-01-01

    We have examined IgG and complement factor C3d deposition on erythrocytes by means of the direct Coombs' test (DAT) and looked for an association with the anaemia seen in falciparum malaria in children living in an area of hyperendemic malaria transmission (in Ghana). In one study (in 1997), 53 out...... parameters were significantly higher in DAT-positive than in DAT-negative patients (P complement binding to erythrocytes was associated with macrophage activation. Plasma levels of haptoglobin, interleukin-10 and tumour necrosis factor-alpha did not vary between the groups....... The studies support the role of complement activation and erythrophagocytosis in the pathogenesis of anaemia in falciparum malaria in African children....

  18. 半边旗药材提取工艺的研究%Study on Extraction Process in Pteris semipinnata L.

    Institute of Scientific and Technical Information of China (English)

    典灵辉; 梁念慈

    2007-01-01

    目的 优选半边旗的提取工艺.方法 采用L9(34)正交试验,考察乙醇浓度(A)、提取时间(B)、提取次数(C)和溶剂用量(D)4个影响因素,以5F(11β-hydroxy-15-oxo-ent-kaur-16-en-19-oic acid)含量为评价指标,并采用薄层扫描法进行含量测定.结果 半边旗回流提取的最佳工艺为A2B2C3D3,即加12倍量70%乙醇,回流提取3次,每次2h.结论 优选出的工艺稳定可行.

  19. EFFECTS OF FIBER SURFACE TREATMENT ON MECHANICALPROPERTIES OF 3D BRAIDED CARBON FIBER/EPOXY COMPOSITE MATERIALS%纤维表面处理对三维编织碳纤维/环氧复合材料力学性能的影响

    Institute of Scientific and Technical Information of China (English)

    王玉果; 王玉林; 万怡灶; 董向红

    2001-01-01

    在对长碳纤维/环氧复合材料(C1/Ep)研究的基础上,重点研究了纤维空气氧化和次氯酸钠氧化对三维编织碳纤维/环氧复合材料(C3D /Ep)力学性能的影响。结果表明.纤维表面处理可显著增强纤维/基体的界面结合强度.使其力学性能大幅度提高。其中.空气氧化效果最为明显。

  20. Complement's participation in acquired immunity

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Leslie, Robert Graham Quinton

    2002-01-01

    B cell receptor for antigen (BCR), a complex composed of the iC3b/C3d fragment-binding complement type 2 receptor (CR2, CD21) and its signaling element CD19 and the IgG-binding receptor FcgammaRIIb (CD32). The positive or negative outcome of signaling through this triad is determined by the context...... in which antigen is seen, be it alone or in association with natural or induced antibodies and/or C3-complement fragments. The aim of this review is to describe the present status of our understanding of complement's participation in acquired immunity and the regulation of autoimmune responses.......The preliminary evidence for the involvement of complement in promoting primary humoral responses dates back over a quarter of a century. However, it is only in the course of the past decade or so that the detailed mechanisms underlying complement's influence have been characterized in depth. It is...

  1. Growth of ZnO nanostructures on Au-coated Si: Influence of growth temperature on growth mechanism and morphology

    DEFF Research Database (Denmark)

    Kumar, Rajendra; McGlynn, E.; Biswas, M.;

    2008-01-01

    ZnO nanostructures were grown on Au-catalyzed Si silicon substrates using vapor phase transport at growth temperatures from 800 to 1150 degrees C. The sample location ensured a low Zn vapor supersaturation during growth. Nanostructures grown at 800 and 850 degrees C showed a faceted rodlike...... growth tended to dominate resulting in the formation of a porous, nanostructured morphology. In all cases growth was seen only on the Au-coated region. Our results show that the majority of the nanostructures grow via a vapor-solid mechanism at low growth temperatures with no evidence of Au nanoparticles...... morphology with mainly one-dimensional (1D) growth along the nanorod axis. Samples grown at intermediate temperatures (900, 950, and 1050 degrees C) in all cases showed significant three dimensional (3D) growth at the base of 1D nanostructures. At higher growth temperatures (1100 and 1150 degrees C) 3D...

  2. Orthogonal Experiment of the Extraction of Triterpenoids from Stems of Hyptis suaveolens with Microwave%微波提取毛老虎茎中总三萜酸的正交实验研究

    Institute of Scientific and Technical Information of China (English)

    黄秀香; 林翠梧; 陈丽芬; 袁霞; 宁自华

    2008-01-01

    目的:研究微波法提取毛老虎茎中总三萜酸的最佳工艺.方法:采用正交实验,考察时间(A)、温度(B)、固液比(C)、NaOH浓度(D)4个因素的影响.结果:微波提取优化工艺条件是A1B2C3D2.结论:微波提取具有提取率高,提取速率快,提取温度低,能量消耗小等特点,用于中草药的提取应用前景广阔.

  3. Synthesis and antibacterial activity of some new 3-hydroxy-2-naphthoic acid hydrazide derivatives for dyeing polyester fabrics

    Directory of Open Access Journals (Sweden)

    Abd El-Galil M. Khalil

    2016-03-01

    Full Text Available Dibenzobarallene was used as a key intermediate for the synthesis of 2-(3-hydroxy-2-naphthoyl-3,4,4a,5,10,10a-hexahydro-1H-5,10-benzenobenzo[g]phthalazine-1,4-dione (2. The previous compound was coupled with the appropriate diazonium chloride to give the corresponding 4-arylazo-2-naphthol derivatives 3a–l. Also, nitration, nitrosation and bromination of compound 2 afforded the corresponding nitro, nitroso and bromo derivatives 4–6, respectively. The synthesized compounds were established and evaluated as antibacterial agents. The results showed clearly that compounds 2, 3a, 3c, 3d, 3g, 3i, 4, 5 and 6 exhibited interesting high activities compared with reference drugs. Also, these compounds were applied to polyester as disperse dyes in which their color measurement and fastness properties were evaluated.

  4. Serum amyloid P component-DNA complexes are decreased in systemic lupus erythematosus. inverse association with anti-dsDNA antibodies

    DEFF Research Database (Denmark)

    Voss, Anne; Nielsen, Ellen Holm; Svehag, Sven Erik;

    2008-01-01

    OBJECTIVE: To study serum levels of serum amyloid P component (SAP) and SAP-DNA complexes in a population-based cohort of patients with systemic lupus erythematosus (SLE). METHODS: The study population comprised 82 unselected patients of predominantly Scandinavian ancestry with SLE according......-DNA-negative patients tended to have lower leukocyte counts and complement C3 levels, and higher erythrocyte sedimentation rates and C3d levels versus SAP-DNA-positive patients. There was an inverse association between the occurrence of anti-double-stranded DNA (anti-dsDNA) antibodies and SAP-DNA complexes. Co......-occurrence of SAP-DNA complexes and anti-dsDNA antibodies was demonstrated in only one SLE patient, implying that 81/82 patients were discordant for the presence of anti-dsDNA antibodies and SAP-DNA complexes. CONCLUSION: The decreased level of SAP-DNA complexes in SLE patients and the inverse relationship between...

  5. Non-Abelian string and particle braiding in topological order: Modular SL (3 ,Z ) representation and (3 +1 ) -dimensional twisted gauge theory

    Science.gov (United States)

    Wang, Juven C.; Wen, Xiao-Gang

    2015-01-01

    String and particle braiding statistics are examined in a class of topological orders described by discrete gauge theories with a gauge group G and a 4-cocycle twist ω4 of G 's cohomology group H4(G ,R /Z ) in three-dimensional space and one-dimensional time (3 +1 D ) . We establish the topological spin and the spin-statistics relation for the closed strings and their multistring braiding statistics. The 3 +1 D twisted gauge theory can be characterized by a representation of a modular transformation group, SL (3 ,Z ) . We express the SL (3 ,Z ) generators Sx y z and Tx y in terms of the gauge group G and the 4-cocycle ω4. As we compactify one of the spatial directions z into a compact circle with a gauge flux b inserted, we can use the generators Sx y and Tx y of an SL (2 ,Z ) subgroup to study the dimensional reduction of the 3D topological order C3 D to a direct sum of degenerate states of 2D topological orders Cb2 D in different flux b sectors: C3 D=⊕bCb2 D . The 2D topological orders Cb2 D are described by 2D gauge theories of the group G twisted by the 3-cocycle ω3 (b ), dimensionally reduced from the 4-cocycle ω4. We show that the SL (2 ,Z ) generators, Sx y and Tx y, fully encode a particular type of three-string braiding statistics with a pattern that is the connected sum of two Hopf links. With certain 4-cocycle twists, we discover that, by threading a third string through two-string unlink into a three-string Hopf-link configuration, Abelian two-string braiding statistics is promoted to non-Abelian three-string braiding statistics.

  6. Direct determination of atom and radical concentrations in thermal reactions of hydrocarbons and other gases

    International Nuclear Information System (INIS)

    This is the sixth annual progress report on this project. During the period covered by the first five reports (June 1976 through December 1980) a shock tube and optical systems to measure H, D and O atom concentrations were built and fully characterized. The performance of our microwave discharge lamps was defined by numerous high-resolution spectroscopic profiles, while empirical calibrations were also made for all three of the above species. H, D and O atom concentrations were measured in gas mixtures containing H2, D2, O2, CD4, C2H6, C2D6, C3H8 and C3D8 in various proportions, and rate constants of several elementary reactions were deduced from the data. During the period covered by this report (January 1 to November 30, 1981) we have made an extensive series of measurements of O concentrations in shock-heated mixtures of C2H6-O2-AR, C2D6-O2-Ar, C3H8-O2-Ar and C3D8-O2-Ar. We have made kinetic modelling calculations for these mixtures to correlate these observed O concentrations, and also our earlier measurements of H and D atom concentrations in similar mixtures, with elementary reaction rate constants. From these calculations we expect to deduce rate constants for a number of reactions. We have also completed a series of O atom measurements in H2-N2O-Ar and D2-N2O-Ar mixtures, from which we have obtained good rate constant data for the reactions O + H2 → OH + H and O + D2 → OD + D. Our immediate future plans involve meaurements of H and D atoms in the dissociation of benzene, toluene, neopentane and their deuterium analogs leading to direct evaluation of rate constants for the unimolecular dissociation of these substances

  7. Direct determination of atom and radical concentrations in thermal reactions of hydrocarbons and other gases. Progress report, December 1, 1981-December 31, 1982

    International Nuclear Information System (INIS)

    This is the seventh annual progress report on this project. During the period covered by the first six reports (June 1976 through December 1980) a shock tube and optical systems to measure H, D and O atom concentrations were built and fully characterized. The performance of our microwave discharge lamps were defined by numerous high-resolution spectroscopic profiles, while empirical calibrations were also made for all three of the above species. H, D and O atom concentrations were measured in gas mixtures containing H2, D2, O2, CD4, C2H6, C2D6, C3H8 and C3D8 in various proportions, and rate constants of several elementary reactions were deduced from the data. During the period covered by this report (December 1, 1981 to December 31, 1982) we have made kinetic modelling calculations to correlate H, D and O atom concentrations measured in shock-heated mixtures of C2H6-O2-Ar, C2D6-O2-Ar, C3H8-O2-Ar and C3D8-O2-Ar. These computations are difficult because there are several reactions for which rate constants are not known, so that it is necessary to do many calculations to completely optimize the results. Consequently, work is still going on with these calculations. We have completed an extensive series of measurements of H and D atom concentrations in pyrolysis experiments of benzene, toluene and neopentane and deuterium analogs, that have led to rate constants for the initial dissociation of these compounds, and for the reaction of H atoms with benzene and toluene

  8. Preparation research of Pazufloxacin Medilate sustained-release Microspheres%甲磺酸帕珠沙星缓释微球的制备工艺研究

    Institute of Scientific and Technical Information of China (English)

    申楼; 余楚钦; 许文杰

    2011-01-01

    Objective: To prepare sustained-release Microspheres of Pazufloxacin Medilate and study preparations how to affect its quality. Methods: By orthogonal design method, the gelatin and chitosan were used as sustained-release material, the proportion of medicine and excipients, the proportion of water and oil, the amount of glutaraldehyde and the stirring rate were used as factors. The drug loading, encapsulation rate and average particle size were used as index to find the best condition. Results: The optimum condition was A2B3C3D2. The proportion of gelatin and chitosan was 25%, the proportion of water and oil was 10%, the amount of glutaraldehyde was 15% and the stirring rate was 800 r/min. Conclusion: The Microspheres were made good shape and large encapsulation rate, its preparation was stable.%目的:制备甲磺酸帕珠沙星缓释微球,探索制备工艺对微球性能的影响.方法:以壳聚糖、明胶为缓释载体材料,采用正交设计.以药物与辅料比、水油相比、交联剂用量及搅拌速率为考察因素,以载药量、包封率、外表形态及平均粒径为指标,筛选最佳工艺条件.结果:优选工艺为A2B3C3D2,即药物与辅料比为25%、水油相比为10%、交联剂用量为15%、搅拌速率为800 r/min.结论:所得微球外表形态良好,包封率高,工艺稳定.

  9. 野鸢尾总黄酮的提取%Study on the process of optimization extraction of total flavonoids of iris dichotoma

    Institute of Scientific and Technical Information of China (English)

    齐建红; 赵咏梅; 方刚; 李丹; 王改改

    2013-01-01

    For the first time,the extraction optimization of total flavonoids in iris dichotoma optimized by orthogonal experiments is reported.The results showed that the order of the factors influencing the optimum extraction technology was:ethanol concentration > extraction temperature > ratio of solid to liquid > extraction time.The best extraction technology conditions was A2B2C3D1,80% ethanol concentration,ratio of solid to liquid 1∶ 20,extraction time 5 min,extraction temperature 90℃,the total flavonoids was 4.007 mg/g.The experiment provided scientific basis of the development and utilization of iris dichotoma flavonoids.%采用正交试验设计对野鸢尾植物中总黄酮的提取工艺进行了优化.结果表明,影响野鸢尾总黄酮的优化提取工艺因素为提取温度>乙醇浓度>料液比>提取时间;优化提取工艺条件为A2B2C3D1,即乙醇体积分数为80%,料液比1∶20(g∶ mL),提取时间为5 min,提取温度为90℃,此条件下总黄酮为4.007 mg/g.

  10. Tanshinone IIA decreases the levels of inflammation induced by Aβ1-42 in brain tissues of Alzheimer's disease model rats.

    Science.gov (United States)

    Lu, Bei-Ling; Li, Jian; Zhou, Jun; Li, Wen-Wen; Wu, Heng-Fei

    2016-08-17

    To study the pathogenesis of Alzheimer's disease (AD) and explore the possible anti-inflammatory mechanism of tanshinone IIA (TanIIA), we evaluated the quantity of neurons and the expression levels of interleukin-1β (IL-1β), IL-6, glial fibrillary acidic protein, CD11b, C1q, C3c, and C3d in brain tissues of AD rats treated with TanIIA. Thirty male Sprague-Dawley rats were randomized into three groups: sham group, TanIIA treatment group, and Aβ1-42 group. Aβ1-42 treatment was performed by injecting Aβ into the hippocampus of rats and then tagged position. Brain tissue morphological structure has been observed with HE staining and the staining of exogenously injected Aβ1-42 was observed by immunohistochemistry, which confirms the success of the Aβ1-42 group. After TanIIA treatment, levels of IL-1β, IL-6, glial fibrillary acidic protein, CD11b, C1q, C3c, and C3d were measured in paraffinized brain tissue sections from all groups by immunohistochemistry staining. The results showed that no 6E10 was detected in the control group, and the difference in the expression levels of 6E10 between the Aβ1-42 group and the TanIIA treatment group was not significant (P>0.05), suggesting that both the Aβ1-42 group and the TanIIA treatment group received the same amount of Aβ. The Aβ1-42 group showed a significant increase in the expression levels of inflammatory markers compared with the sham group (Pastrocytes and microglial cells, and induced a partial decrease in complement molecules in the brain of AD rats. These findings suggested that TanIIA may represent a potential therapeutic treatment in neurodegenerative diseases such as AD to support the survival of neurons by reducing expression levels of inflammatory factors. PMID:27348015

  11. 黑芝麻山药酥的研制%Preparation of Black Sesame and Chinese Yam Cookies

    Institute of Scientific and Technical Information of China (English)

    贾娟; 韩文凤; 郭志芳

    2013-01-01

      The black sesame and Chinese yam cookies which was made from black sesame seed, Chinese yam powder, sugar, liquorice, palm oil, edible oil, eggs and other materials as raw material was determined.The best formula with the sensory quality as evaluation targets was obtained by the single and orthogonal experiment.The best formula of oil skin was A3B4C3D2, which was Chinese yam 55%,licorice juice 40%,Sugar 28%,palm oil 30%.The best formula of stuffing was A2B2C2, which was Sugar 25%,plant oil 30%, carrageenan 0.6%.%  以黑芝麻、山药粉、蔗糖、甘草、棕榈油、食用油、鸡蛋等为原辅料,依据感官质量作为评价指标,通过单因素试验和正交试验确定出加工黑芝麻山药酥的油皮最佳组合A3B4C3D2,即当山药粉的添加量为55%,甘草汁的添加量40%,蔗糖的添加量为28%,棕榈油30%时,馅料的最佳组合A2B2C2,即蔗糖25%,植物油30%,卡拉胶为0.6%时产品的质量最好。

  12. Crystal-field analysis for RE3+ ions in laser materials: III. Energy levels for Nd3+ and Er3+ ions in LaAlO3, YAlO3, and LaGaO3 single crystals – Combined approach to low symmetry crystal field parameters

    International Nuclear Information System (INIS)

    Display Omitted Highlights: ► CF analysis of energy levels for Nd3+ and Er3+ ions in ABO3 crystals is presented. ► Combined ADS/SPM strategy is employed. ► Its usefulness for successful analysis of low-symmetry systems is proved. ► Structural relationships between different ion–host systems are emphasized. - Abstract: Crystal field (CF) analysis of energy levels for Nd3+ and Er3+ ions in LaAlO3, YAlO3, and LaGaO3 single crystals is presented. It is shown that a combined approach comprising the ascent/descent in symmetry (ADS) method combined with superposition model (SPM) analysis can be successfully used for analysis of low-symmetry systems. The present ADS/SPM approach is less labor and time consuming as compared, e.g., with Monte-Carlo method and it also allows maintaining the relationship between the crystallographic axis system and the nominal axis systems of fitted CFP sets. For orthogallates and orthoaluminates the actual Cs symmetry, resulting from distortion of perovskite structure, may be successfully approximated for both systems by the ADS chain C4v ↔ C3 (D3) ↔ Cs or C3 (D3) ↔ Cs symmetry. The possibility of using of approximated symmetries for orthogallates or orthoaluminates can be useful for interpretation of energy levels for this family of compounds of technological importance, particularly in the case when the number of available experimental energy levels is insufficient for full Cs parameterization. The novel aspect of the combined ADS/SPM approach is that possible higher symmetry approximations employing also the axis systems oriented differently than for the actual symmetry are searched for, taking advantages of the transformation properties of CF parameters sets.

  13. Complement C3 deficiency attenuates chronic hypoxia-induced pulmonary hypertension in mice.

    Directory of Open Access Journals (Sweden)

    Eileen M Bauer

    Full Text Available Evidence suggests a role of both innate and adaptive immunity in the development of pulmonary arterial hypertension. The complement system is a key sentry of the innate immune system and bridges innate and adaptive immunity. To date there are no studies addressing a role for the complement system in pulmonary arterial hypertension.Immunofluorescent staining revealed significant C3d deposition in lung sections from IPAH patients and C57Bl6/J wild-type mice exposed to three weeks of chronic hypoxia to induce pulmonary hypertension. Right ventricular systolic pressure and right ventricular hypertrophy were increased in hypoxic vs. normoxic wild-type mice, which were attenuated in C3-/- hypoxic mice. Likewise, pulmonary vascular remodeling was attenuated in the C3-/- mice compared to wild-type mice as determined by the number of muscularized peripheral arterioles and morphometric analysis of vessel wall thickness. The loss of C3 attenuated the increase in interleukin-6 and intracellular adhesion molecule-1 expression in response to chronic hypoxia, but not endothelin-1 levels. In wild-type mice, but not C3-/- mice, chronic hypoxia led to platelet activation as assessed by bleeding time, and flow cytometry of platelets to determine cell surface P-selectin expression. In addition, tissue factor expression and fibrin deposition were increased in the lungs of WT mice in response to chronic hypoxia. These pro-thrombotic effects of hypoxia were abrogated in C3-/- mice.Herein, we provide compelling genetic evidence that the complement system plays a pathophysiologic role in the development of PAH in mice, promoting pulmonary vascular remodeling and a pro-thrombotic phenotype. In addition we demonstrate C3d deposition in IPAH patients suggesting that complement activation plays a role in the development of PAH in humans.

  14. Isotope effects in trapping-mediated chemisorption of ethane and propane on Ir(110)

    International Nuclear Information System (INIS)

    We compare here recent results of molecular beam investigations of the initial probability of trapping-mediated C endash H and C endash D bond cleavage of C2H6, C2D6, C3H8, and C3D8 on Ir(110) at low beam translational energy and surface temperatures, TS, from 85 to 800 K. Each of these systems is highly reactive at low TS and displays decreasing reactivity with increasing TS. Measurements of the initial probability of trapping-mediated chemisorption for both ethane and propane reveal an isotope effect, which we attribute to zero-point energy differences, with the perhydrido-species exhibiting greater reactivity at a given TS. A difference in activation energies for desorption vs reaction (C endash D bond cleavage) for C2D6 has been found to be Ed endash Er=1.8±0.3 kcal/mol, cf. Ed endash Er=2.2 kcal/mol for C endash H bond cleavage of C2H6. For the trapping-mediated dissociative chemisorption of propane on Ir(110), Ed endash Er=4.2 kcal/mol for C endash H bond cleavage of C3H8, and Ed endash Er=3.2 kcal/mol for C endash D bond cleavage of C3D8. A quantitative analysis of the initial probability of trapping-mediated dissociative chemisorption of ethane and propane on Ir(110), within the context of a classical kinetic model of barrier crossing from the physically adsorbed state to the dissociatively chemisorbed state, provides the most reasonable description of the observed adsorption behavior. copyright 1996 American Institute of Physics

  15. Intra-operative computer navigation guided cervical pedicle screw insertion in thirty-three complex cervical spine deformities

    Directory of Open Access Journals (Sweden)

    S Rajasekaran

    2010-01-01

    Full Text Available Background: Cervical pedicle screw fixation is challenging due to the small osseous morphometrics and the close proximity of neurovascular elements. Computer navigation has been reported to improve the accuracy of pedicle screw placement. There are very few studies assessing its efficacy in the presence of deformity. Also cervical pedicle screw insertion in children has not been described before. We evaluated the safety and accuracy of Iso-C 3D-navigated pedicle screws in the deformed cervical spine. Materials and Methods: Thirty-three patients including 15 children formed the study group. One hundred and forty-five cervical pedicle screws were inserted using Iso-C 3D-based computer navigation in patients undergoing cervical spine stabilization for craniovertebral junction anomalies, cervico-thoracic deformities and cervical instabilities due to trauma, post-surgery and degenerative disorders. The accuracy and containment of screw placement was assessed from postoperative computerized tomography scans. Results: One hundred and thirty (89.7% screws were well contained inside the pedicles. Nine (6.1% Type A and six (4.2% Type B pedicle breaches were observed. In 136 levels, the screws were inserted in the classical description of pedicle screw application and in nine deformed vertebra, the screws were inserted in a non-classical fashion, taking purchase of the best bone stock. None of them had a critical breach. No patient had any neurovascular complications. Conclusion: Iso-C navigation improves the safety and accuracy of pedicle screw insertion and is not only successful in achieving secure pedicle fixation but also in identifying the best available bone stock for three-column bone fixation in altered anatomy. The advantages conferred by cervical pedicle screws can be extended to the pediatric population also.

  16. Activation of Complement Following Total Hip Replacement.

    Science.gov (United States)

    Thordardottir, S; Vikingsdottir, T; Bjarnadottir, H; Jonsson, H; Gudbjornsson, B

    2016-03-01

    The aim of this study was to investigate whether complement activation, via the classical and alternative pathways, occurs following a cemented total hip replacement (THR) surgery due to osteoarthritis. Blood samples were collected systematically from 12 patients - six male and six women, with a median age of 75 (range: 59-90 years) - preoperatively, 6 h post-operatively and on the first, second and third post-operative day. Total function of classical (CH50) and alternative pathways (AH50) was evaluated, along with the determination of serum concentrations of the complement proteins C3, C4, C3d, the soluble terminal complement complex (sTCC) sC5b-9, as well as C-reactive protein (CRP) and albumin. Measurements of CRP and albumin levels elucidated a marked inflammatory response following the operation. The CH50, AH50 and C3 and C4 levels were significantly lower 6 h after the surgery compared with the preoperative levels, but elevated above the preoperative levels during the following 3 days. The complement activation product C3d levels increased continually during the whole observation period, from 13.5 AU/ml (range: 8-19 AU/ml) preoperative to 20 AU/ml (range: 12-34 AU/ml) on the third post-operative day. Furthermore, we observed an increase in the sC5b-9 levels between the preoperative and the third post-operative day. These results demonstrate a significant activation of the complement system following cemented THR. Further studies are needed to elucidate the time frame and the pathogenic role of this observed complement activation.

  17. Processing Technology of Functional Soybean Drinks Made from Kelp, Coix Seed, Red Beans and Soy%海带·薏米·红豆·黄豆复合保健豆浆饮料的新工艺配方研究

    Institute of Scientific and Technical Information of China (English)

    唐辉

    2013-01-01

    [Objective] To study optimum formula and technique of compound functional drink made from kelp,coix seed,red beans and soy.[Method] The orthogonal experiment and fuzzy mathematic judgment were adopted to obtain the optimum formula.[Result] The optimum formula is A1B3C3D3,namely kelp 5 g,coix seed 20 g,red beans 50 g,soybean 80 g,adding water 1 200 ml.[Conclusion] The study provide reference basis for production of compound health soybean milk beverage.%[目的]对海带、薏米、红豆、黄豆复合保健豆浆的最佳配方及其工艺进行研究.[方法]应用正交试验设计方案和模糊数学评判确定出海带、薏米、红豆、黄豆复合保健豆浆的最佳工艺配方.[结果]试验表明,海带、薏米、红豆、黄豆复合保健豆浆的最佳工艺配方为A1B3C3D3,即海带5 g、薏米20 g、红豆50 g、黄豆80 g,加水1 200 ml磨出的豆浆口味最佳.[结论]研究为豆浆饮料增添了一个新的品种,同时可为该复合保健豆浆饮料的批量生产提供参考依据.

  18. Ultrasonic-assisted extraction technology of papaya seed oil%超声波辅助提取木瓜籽油的工艺研究

    Institute of Scientific and Technical Information of China (English)

    王鑫; 赵梅; 慕鸿雁

    2015-01-01

    Papaya seedoil was extracted by ultrasound method. Theoptimal ultrasound–assisted extraction processingconditions were explored by single–factor andorthogonal experiments. The result showed that theorderof primary and secondary factors that effected the extraction rateof papaya seed oil wasB>C>A>D,that was to say the extraction temperature was the most important,followed by extraction time,ratioof solid–liquid and ultrasonic power. Theoptimumconditionof extraction rate of papaya seedoil wasA2B1C3D1,that was to say ratioof solid–liquid was 1∶10 g/mL,extraction temperature was 50℃,extraction time was 30 minutes and ultrasonic power was 175 W. Under this condition,the yieldof papaya seedoil was up to 29.36%.%采用超声波辅助提取木瓜籽油,并用单因素试验和正交试验筛选最佳提取条件。结果表明:影响木瓜籽油出油率的因素主次顺序是B>C>A>D,即超声温度>超声时间>料液比>超声波功率。最佳提取工艺条件为,A2B1C3D1,即料液比1∶10 g/mL、超声温度50℃、超声时间30 min、超声功率175 W。在此工艺条件下,木瓜籽油出油率为29.36%。

  19. The 15 SCR flexible extracellular domains of human complement receptor type 2 can mediate multiple ligand and antigen interactions.

    Science.gov (United States)

    Gilbert, Hannah E; Asokan, Rengasamy; Holers, V Michael; Perkins, Stephen J

    2006-10-01

    Complement receptor type 2 (CR2, CD21) is a cell surface protein that links the innate and adaptive immune response during the activation of B cells. The extracellular portion of CR2 comprises 15 or 16 short complement regulator (SCR) domains, for which the overall arrangement in solution is unknown. This was determined by constrained scattering and ultracentrifugation modelling. The radius of gyration of CR2 SCR 1-15 was determined to be 11.5 nm by both X-ray and neutron scattering, and that of its cross-section was 1.8 nm. The distance distribution function P(r) showed that the overall length of CR2 SCR 1-15 was 38 nm. Sedimentation equilibrium curve fits gave a mean molecular weight of 135,000 (+/- 13,000) Da, in agreement with a fully glycosylated structure. Velocity experiments using the g*(s) derivative method gave a sedimentation coefficient of 4.2 (+/- 0.1) S. In order to construct a model of CR2 SCR 1-15 for constrained fitting, homology models for the 15 SCR domains were combined with randomised linker peptides generated by molecular dynamics simulations. Using an automated procedure, the analysis of 15,000 possible CR2 SCR 1-15 models showed that only those models in which the 15 SCR domains were flexible but partially folded back accounted for the scattering and sedimentation data. The best-fit CR2 models provided a visual explanation for the versatile interaction of CR2 with four ligands C3d, CD23, gp350 and IFN-alpha. The flexible location of CR2 SCR 1-2 is likely to facilitate interactions of C3d-antigen complexes with the B cell receptor.

  20. Modelling staphylococcal pneumonia in a human 3D lung tissue model system delineates toxin-mediated pathology.

    Science.gov (United States)

    Mairpady Shambat, Srikanth; Chen, Puran; Nguyen Hoang, Anh Thu; Bergsten, Helena; Vandenesch, Francois; Siemens, Nikolai; Lina, Gerard; Monk, Ian R; Foster, Timothy J; Arakere, Gayathri; Svensson, Mattias; Norrby-Teglund, Anna

    2015-11-01

    Staphylococcus aureus necrotizing pneumonia is recognized as a toxin-mediated disease, yet the tissue-destructive events remain elusive, partly as a result of lack of mechanistic studies in human lung tissue. In this study, a three-dimensional (3D) tissue model composed of human lung epithelial cells and fibroblasts was used to delineate the role of specific staphylococcal exotoxins in tissue pathology associated with severe pneumonia. To this end, the models were exposed to the mixture of exotoxins produced by S. aureus strains isolated from patients with varying severity of lung infection, namely necrotizing pneumonia or lung empyema, or to purified toxins. The necrotizing pneumonia strains secreted high levels of α-toxin and Panton-Valentine leukocidin (PVL), and triggered high cytotoxicity, inflammation, necrosis and loss of E-cadherin from the lung epithelium. In contrast, the lung empyema strain produced moderate levels of PVL, but negligible amounts of α-toxin, and triggered limited tissue damage. α-toxin had a direct damaging effect on the epithelium, as verified using toxin-deficient mutants and pure α-toxin. Moreover, PVL contributed to pathology through the lysis of neutrophils. A combination of α-toxin and PVL resulted in the most severe epithelial injury. In addition, toxin-induced release of pro-inflammatory mediators from lung tissue models resulted in enhanced neutrophil migration. Using a collection of 31 strains from patients with staphylococcal pneumonia revealed that strains producing high levels of α-toxin and PVL were cytotoxic and associated with fatal outcome. Also, the strains that produced the highest toxin levels induced significantly greater epithelial disruption. Of importance, toxin-mediated lung epithelium destruction could be inhibited by polyspecific intravenous immunoglobulin containing antibodies against α-toxin and PVL. This study introduces a novel model system for study of staphylococcal pneumonia in a human setting. The

  1. Influence of SLC22A1 rs622342 genetic polymorphism on metformin response in South Indian type 2 diabetes mellitus patients.

    Science.gov (United States)

    Umamaheswaran, Gurusamy; Praveen, Ramakrishnan Geethakumari; Damodaran, Solai Elango; Das, Ashok Kumar; Adithan, Chandrasekaran

    2015-11-01

    Metformin is an oral antidiabetic drug, commonly used for treating type 2 diabetes mellitus (T2DM) patients. It is transported into the hepatocytes by polyspecific organic cation transporter 1, which is encoded by the gene SLC22A1. It has been hypothesized that genetic variations of SLC22A1 gene will influence inter-individual variation in glucose lowering efficacy of metformin. Previous studies have demonstrated this in other populations with conflicting results, but it remains to be elucidated in Indian population. Henceforth, the objective of the study was to evaluate the impact of SLC22A1 rs622342 gene polymorphism on the clinical efficacy of metformin in South Indian T2DM patients. A total of 122 newly detected, treatment naive T2DM patients of either sex were included in this study. The patients were started on metformin monotherapy and followed up for 12 weeks. Genotype was determined using qRT-PCR. Before and after treatment with metformin, body mass index (BMI), serum lipid profile, glycated hemoglobin (HbA1c), fasting and postprandial glucose level, and blood pressure (BP) were measured. The study cohort mean age was 49.57 ± 9.88 years. Of the 122 T2DM patients, 93 were classified as responders and 29 as non-responders based on fall in HbA1c levels. Interestingly, carriers of one variant allele 'C' (AC) of rs622342 polymorphism were less among the responders than those who did not (44.8 vs. 22.6 %). The response was even lesser (13.8 vs. 4.3 %) in carriers of two copies of "C" allele (CC). On the contrary, patients with two copies of allele 'A' (AA) had 5.6 times greater chance of responding to metformin treatment. A similar trend was observed when the proportion was analyzed under different genetic models (OR 3.85, 95 % CI 1.61-9.19 for dominant; OR 3.56, 95 % CI 0.83-15.26 for recessive; OR 0.35, 95 % CI 0.14-0.86 for over-dominant; and OR 4.10, 95 % CI 1.78-9.43 for additive). Further, metformin showed significant beneficial effects on BMI, HbA1c, FPG

  2. Modelling staphylococcal pneumonia in a human 3D lung tissue model system delineates toxin-mediated pathology

    Directory of Open Access Journals (Sweden)

    Srikanth Mairpady Shambat

    2015-11-01

    Full Text Available Staphylococcus aureus necrotizing pneumonia is recognized as a toxin-mediated disease, yet the tissue-destructive events remain elusive, partly as a result of lack of mechanistic studies in human lung tissue. In this study, a three-dimensional (3D tissue model composed of human lung epithelial cells and fibroblasts was used to delineate the role of specific staphylococcal exotoxins in tissue pathology associated with severe pneumonia. To this end, the models were exposed to the mixture of exotoxins produced by S. aureus strains isolated from patients with varying severity of lung infection, namely necrotizing pneumonia or lung empyema, or to purified toxins. The necrotizing pneumonia strains secreted high levels of α-toxin and Panton-Valentine leukocidin (PVL, and triggered high cytotoxicity, inflammation, necrosis and loss of E-cadherin from the lung epithelium. In contrast, the lung empyema strain produced moderate levels of PVL, but negligible amounts of α-toxin, and triggered limited tissue damage. α-toxin had a direct damaging effect on the epithelium, as verified using toxin-deficient mutants and pure α-toxin. Moreover, PVL contributed to pathology through the lysis of neutrophils. A combination of α-toxin and PVL resulted in the most severe epithelial injury. In addition, toxin-induced release of pro-inflammatory mediators from lung tissue models resulted in enhanced neutrophil migration. Using a collection of 31 strains from patients with staphylococcal pneumonia revealed that strains producing high levels of α-toxin and PVL were cytotoxic and associated with fatal outcome. Also, the strains that produced the highest toxin levels induced significantly greater epithelial disruption. Of importance, toxin-mediated lung epithelium destruction could be inhibited by polyspecific intravenous immunoglobulin containing antibodies against α-toxin and PVL. This study introduces a novel model system for study of staphylococcal pneumonia in a

  3. Influence of SLC22A1 rs622342 genetic polymorphism on metformin response in South Indian type 2 diabetes mellitus patients.

    Science.gov (United States)

    Umamaheswaran, Gurusamy; Praveen, Ramakrishnan Geethakumari; Damodaran, Solai Elango; Das, Ashok Kumar; Adithan, Chandrasekaran

    2015-11-01

    Metformin is an oral antidiabetic drug, commonly used for treating type 2 diabetes mellitus (T2DM) patients. It is transported into the hepatocytes by polyspecific organic cation transporter 1, which is encoded by the gene SLC22A1. It has been hypothesized that genetic variations of SLC22A1 gene will influence inter-individual variation in glucose lowering efficacy of metformin. Previous studies have demonstrated this in other populations with conflicting results, but it remains to be elucidated in Indian population. Henceforth, the objective of the study was to evaluate the impact of SLC22A1 rs622342 gene polymorphism on the clinical efficacy of metformin in South Indian T2DM patients. A total of 122 newly detected, treatment naive T2DM patients of either sex were included in this study. The patients were started on metformin monotherapy and followed up for 12 weeks. Genotype was determined using qRT-PCR. Before and after treatment with metformin, body mass index (BMI), serum lipid profile, glycated hemoglobin (HbA1c), fasting and postprandial glucose level, and blood pressure (BP) were measured. The study cohort mean age was 49.57 ± 9.88 years. Of the 122 T2DM patients, 93 were classified as responders and 29 as non-responders based on fall in HbA1c levels. Interestingly, carriers of one variant allele 'C' (AC) of rs622342 polymorphism were less among the responders than those who did not (44.8 vs. 22.6 %). The response was even lesser (13.8 vs. 4.3 %) in carriers of two copies of "C" allele (CC). On the contrary, patients with two copies of allele 'A' (AA) had 5.6 times greater chance of responding to metformin treatment. A similar trend was observed when the proportion was analyzed under different genetic models (OR 3.85, 95 % CI 1.61-9.19 for dominant; OR 3.56, 95 % CI 0.83-15.26 for recessive; OR 0.35, 95 % CI 0.14-0.86 for over-dominant; and OR 4.10, 95 % CI 1.78-9.43 for additive). Further, metformin showed significant beneficial effects on BMI, HbA1c, FPG

  4. Frequency patterns of T-cell exposed motifs in immunoglobulin heavy chain peptides presented by MHCs

    Directory of Open Access Journals (Sweden)

    Robert D. Bremel

    2014-10-01

    Full Text Available Immunoglobulins are highly diverse protein sequences that are processed and presented to T-cells by B-cells and other antigen presenting cells. We examined a large dataset of immunoglobulin heavy chain variable regions (IGHV to assess the diversity of T-cell exposed motifs (TCEM. TCEM comprise those amino acids in a MHC-bound peptide which face outwards, surrounded by the MHC histotope, and which engage the T-cell receptor. Within IGHV there is a distinct pattern of predicted MHC class II binding and a very high frequency of re-use of the TCEMs. The re-use frequency indicates that only a limited number of different cognate T-cells are required to engage many different clonal B-cells. The amino acids in each outward-facing TCEM are intercalated with the amino acids of inward-facing MHC groove-exposed motifs (GEM. Different GEM may have differing, allele-specific, MHC binding affinities. The intercalation of TCEM and GEM in a peptide allows for a vast combinatorial repertoire of epitopes, each eliciting a different response. Outcome of T-cell receptor binding is determined by overall signal strength, which is a function of the number of responding T-cells and the duration of engagement. Hence, the frequency of T-cell exposed motif re-use appears to be an important determinant of whether a T-cell response is stimulatory or suppressive. The frequency distribution of TCEMs implies that somatic hypermutation is followed by clonal expansion that develop along repeated pathways. The observations of TCEM and GEM derived from immunoglobulins suggest a relatively simple, yet powerful, mechanism to correlate T-cell polyspecificity, through re-use of TCEMs, with a very high degree of specificity achieved by combination with a diversity of GEMs. The frequency profile of TCEMs also points to an economical mechanism for maintaining T-cell memory, recall, and self-discrimination based on an endogenously generated profile of motifs.

  5. Interaction of environmental contaminants with zebrafish organic anion transporting polypeptide, Oatp1d1 (Slco1d1)

    International Nuclear Information System (INIS)

    Polyspecific transporters from the organic anion transporting polypeptide (OATP/Oatp) superfamily mediate the uptake of a wide range of compounds. In zebrafish, Oatp1d1 transports conjugated steroid hormones and cortisol. It is predominantly expressed in the liver, brain and testes. In this study we have characterized the transport of xenobiotics by the zebrafish Oatp1d1 transporter. We developed a novel assay for assessing Oatp1d1 interactors using the fluorescent probe Lucifer yellow and transient transfection in HEK293 cells. Our data showed that numerous environmental contaminants interact with zebrafish Oatp1d1. Oatp1d1 mediated the transport of diclofenac with very high affinity, followed by high affinity towards perfluorooctanesulfonic acid (PFOS), nonylphenol, gemfibrozil and 17α-ethinylestradiol; moderate affinity towards carbaryl, diazinon and caffeine; and low affinity towards metolachlor. Importantly, many environmental chemicals acted as strong inhibitors of Oatp1d1. A strong inhibition of Oatp1d1 transport activity was found by perfluorooctanoic acid (PFOA), chlorpyrifos-methyl, estrone (E1) and 17β-estradiol (E2), followed by moderate to low inhibition by diethyl phthalate, bisphenol A, 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4 tetrahydronapthalene and clofibrate. In this study we identified Oatp1d1 as a first Solute Carrier (SLC) transporter involved in the transport of a wide range of xenobiotics in fish. Considering that Oatps in zebrafish have not been characterized before, our work on zebrafish Oatp1d1 offers important new insights on the understanding of uptake processes of environmental contaminants, and contributes to the better characterization of zebrafish as a model species. - Highlights: • We optimized a novel assay for determination of Oatp1d1 interactors • Oatp1d1 is the first SLC characterized fish xenobiotic transporter • PFOS, nonylphenol, diclofenac, EE2, caffeine are high affinity Oatp1d1substrates • PFOA, chlorpyrifos

  6. Interaction of environmental contaminants with zebrafish organic anion transporting polypeptide, Oatp1d1 (Slco1d1)

    Energy Technology Data Exchange (ETDEWEB)

    Popovic, Marta; Zaja, Roko [Laboratory for Molecular Ecotoxicology, Division for Marine and Environmental Research, Rudjer Boskovic Institute, Bijenicka 54, 10 000 Zagreb (Croatia); Fent, Karl [University of Applied Sciences Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); Swiss Federal Institute of Technology (ETH Zürich), Department of Environmental System Sciences, Institute of Biogeochemistry and Pollution Dynamics, CH-8092 Zürich (Switzerland); Smital, Tvrtko, E-mail: smital@irb.hr [Laboratory for Molecular Ecotoxicology, Division for Marine and Environmental Research, Rudjer Boskovic Institute, Bijenicka 54, 10 000 Zagreb (Croatia)

    2014-10-01

    Polyspecific transporters from the organic anion transporting polypeptide (OATP/Oatp) superfamily mediate the uptake of a wide range of compounds. In zebrafish, Oatp1d1 transports conjugated steroid hormones and cortisol. It is predominantly expressed in the liver, brain and testes. In this study we have characterized the transport of xenobiotics by the zebrafish Oatp1d1 transporter. We developed a novel assay for assessing Oatp1d1 interactors using the fluorescent probe Lucifer yellow and transient transfection in HEK293 cells. Our data showed that numerous environmental contaminants interact with zebrafish Oatp1d1. Oatp1d1 mediated the transport of diclofenac with very high affinity, followed by high affinity towards perfluorooctanesulfonic acid (PFOS), nonylphenol, gemfibrozil and 17α-ethinylestradiol; moderate affinity towards carbaryl, diazinon and caffeine; and low affinity towards metolachlor. Importantly, many environmental chemicals acted as strong inhibitors of Oatp1d1. A strong inhibition of Oatp1d1 transport activity was found by perfluorooctanoic acid (PFOA), chlorpyrifos-methyl, estrone (E1) and 17β-estradiol (E2), followed by moderate to low inhibition by diethyl phthalate, bisphenol A, 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4 tetrahydronapthalene and clofibrate. In this study we identified Oatp1d1 as a first Solute Carrier (SLC) transporter involved in the transport of a wide range of xenobiotics in fish. Considering that Oatps in zebrafish have not been characterized before, our work on zebrafish Oatp1d1 offers important new insights on the understanding of uptake processes of environmental contaminants, and contributes to the better characterization of zebrafish as a model species. - Highlights: • We optimized a novel assay for determination of Oatp1d1 interactors • Oatp1d1 is the first SLC characterized fish xenobiotic transporter • PFOS, nonylphenol, diclofenac, EE2, caffeine are high affinity Oatp1d1substrates • PFOA, chlorpyrifos

  7. Mixed-species associations in cuxiús (genus Chiropotes).

    Science.gov (United States)

    Shaffer, Christopher A; Barnett, Adrian A; Gregory, Tremaine; de Melo, Fabiano; Moreira, Leandro; Alvim, Thiago H G; Moura, Viviane S; Filó, Anderson; Cardoso, Tatiane; Port-Carvalho, Marcio; Santos, Ricardo Rodrigues dos; Boyle, Sarah A

    2016-05-01

    Polyspecific or mixed-species associations, where two or more species come together to forage and travel as a unit, have been reported in many primate species. These associations appear to offer a number of benefits to the species involved including increased foraging efficiency and decreased risk of predation. While several researchers have suggested that cuxiús (genus Chiropotes) form mixed-species associations, previous studies have not identified the circumstances under which cuxiús form associations or whether they form associations more often than would be expected by chance. Here we present data on the formation of mixed-species associations by four species of cuxiús at eight different sites in Brazil, Suriname, and Guyana. We analyzed data from two of the study sites, (Biological Dynamics of Forest Fragments Project (BDFFP), Brazil and the Upper Essequibo Conservation Concession (UECC), Guyana, to assess whether associations occurred more than would be expected by chance encounters and identify the factors influencing their formation. Cuxiús showed a high degree of inter-site variation in the frequency of time spent in association (ranging from 2 to 26% of observation time) and duration of associations (mean duration from 22 min to 2.5 hr). Sapajus apella was the most common association partner at most sites. At BDFFP, cuxiús formed associations more frequently but not for longer duration than expected by chance. For much of the year at UECC, associations were not more frequent or longer than chance. However, during the dry season, cuxiús formed associations with S. apella significantly more often and for longer duration than predicted by chance. Cuxiús at UECC formed associations significantly more often when in smaller subgroups and when foraging for insects, and alarm called significantly less frequently during associations. We suggest cuxiús form mixed-species associations at some sites as an adaptive strategy to decrease predation risk and

  8. Antibody producing B lineage cells invade the central nervous system predominantly at the time of and triggered by acute Epstein-Barr virus infection: A hypothesis on the origin of intrathecal immunoglobulin synthesis in multiple sclerosis.

    Science.gov (United States)

    Otto, Carolin; Hofmann, Jörg; Ruprecht, Klemens

    2016-06-01

    Patients with multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS), typically have an intrathecal synthesis of immunoglobulin (Ig)G. Intrathecal IgG is produced by B lineage cells that entered the CNS, but why and when these cells invade the CNS of patients with MS is unknown. The intrathecal IgG response in patients with MS is polyspecific and part of it is directed against different common viruses (e.g. measles virus, rubella virus, varicella zoster virus). Strong and consistent evidence suggests an association of MS and Epstein-Barr virus (EBV) infection and EBV seroprevalence in patients with MS is practically 100%. However, intriguingly, despite of the universal EBV seroprevalence, the frequency of intrathecally produced IgG to EBV in patients with MS is much lower than that of intrathecally produced IgG to other common viruses. The acute phase of primary EBV infection is characterized by a strong polyclonal B cell activation. As typical for humoral immune responses against viruses, EBV specific IgG is produced only with a temporal delay after acute EBV infection. Aiming to put the above facts into a logical structure, we here propose the hypothesis that in individuals going on to develop MS antibody producing B lineage cells invade the CNS predominantly at the time of and triggered by acute primary EBV infection. Because at the time of acute EBV infection EBV IgG producing B lineage cells have not yet occurred, the hypothesis could explain the universal EBV seroprevalence and the low frequency of intrathecally produced IgG to EBV in patients with MS. Evidence supporting the hypothesis could be provided by large prospective follow-up studies of individuals with symptomatic primary EBV infection (infectious mononucleosis). Furthermore, the clarification of the molecular mechanism underlying an EBV induced invasion of B lineage cells into the CNS of individuals going on to develop MS could corroborate it, too. If true, our

  9. Tick parasites of rodents in Romania: host preferences, community structure and geographical distribution

    Directory of Open Access Journals (Sweden)

    Mihalca Andrei D

    2012-11-01

    Full Text Available Abstract Background Ticks are among the most important vectors of zoonotic diseases in temperate regions of Europe, with widespread distribution and high densities, posing an important medical risk. Most ticks feed on a variety of progressively larger hosts, with a large number of small mammal species typically harbouring primarily the immature stages. However, there are certain Ixodidae that characteristically attack micromammals also during their adult stage. Rodents are widespread hosts of ticks, important vectors and competent reservoirs of tick-borne pathogens. Micromammal-tick associations have been poorly studied in Romania, and our manuscript shows the results of a large scale study on tick infestation epidemiology in rodents from Romania. Methods Rodents were caught using snap-traps in a variety of habitats in Romania, between May 2010 and November 2011. Ticks were individually collected from these rodents and identified to species and development stage. Frequency, mean intensity, prevalence and its 95% confidence intervals were calculated using the EpiInfo 2000 software. A p value of Results We examined 423 rodents (12 species collected from six counties in Romania for the presence of ticks. Each collected tick was identified to species level and the following epidemiological parameters were calculated: prevalence, mean intensity and mean abundance. The total number of ticks collected from rodents was 483, with eight species identified: Ixodes ricinus, I. redikorzevi, I. apronophorus, I. trianguliceps, I. laguri, Dermacentor marginatus, Rhipicephalus sanguineus and Haemaphysalis sulcata. The overall prevalence of tick infestation was 29.55%, with a mean intensity of 3.86 and a mean abundance of 1.14. Only two polyspecific infestations were found: I. ricinus + I. redikorzevi and I. ricinus + D. marginatus. Conclusions Our study showed a relatively high diversity of ticks parasitizing rodents in Romania. The most common tick in rodents

  10. Randomised controlled double-blind non-inferiority trial of two antivenoms for saw-scaled or carpet viper (Echis ocellatus envenoming in Nigeria.

    Directory of Open Access Journals (Sweden)

    Isa S Abubakar

    Full Text Available BACKGROUND: In West Africa, envenoming by saw-scaled or carpet vipers (Echis ocellatus causes great morbidity and mortality, but there is a crisis in supply of effective and affordable antivenom (ISRCTN01257358. METHODS: In a randomised, double-blind, controlled, non-inferiority trial, "EchiTAb Plus-ICP" (ET-Plus equine antivenom made by Instituto Clodomiro Picado was compared to "EchiTAb G" (ET-G ovine antivenom made by MicroPharm, which is the standard of care in Nigeria and was developed from the original EchiTAb-Fab introduced in 1998. Both are caprylic acid purified whole IgG antivenoms. ET-G is monospecific for Echis ocellatus antivenom (initial dose 1 vial and ET-Plus is polyspecific for E. ocellatus, Naja nigricollis and Bitis arietans (initial dose 3 vials. Both had been screened by pre-clinical and preliminary clinical dose-finding and safety studies. Patients who presented with incoagulable blood, indicative of systemic envenoming by E. ocellatus, were recruited in Kaltungo, north-eastern Nigeria. Those eligible and consenting were randomly allocated with equal probability to receive ET-Plus or ET-G. The primary outcome was permanent restoration of blood coagulability 6 hours after the start of treatment, assessed by a simple whole blood clotting test repeated 6, 12, 18, 24 and 48 hr after treatment. Secondary (safety outcomes were the incidences of anaphylactic, pyrogenic and late serum sickness-type antivenom reactions. FINDINGS: Initial doses permanently restored blood coagulability at 6 hours in 161/194 (83.0% of ET-Plus and 156/206 (75.7% of ET-G treated patients (Relative Risk [RR] 1.10 one-sided 95% CI lower limit 1.01; P = 0.05. ET-Plus caused early reactions on more occasions than did ET-G [50/194 (25.8% and 39/206 (18.9% respectively RR (1.36 one-sided 95% CI 1.86 upper limit; P = 0.06. These reactions were classified as severe in 21 (10.8% and 11 (5.3% of patients, respectively. CONCLUSION: At these doses, ET-Plus was

  11. Molecular characterization of zebrafish Oatp1d1 (Slco1d1), a novel organic anion-transporting polypeptide.

    Science.gov (United States)

    Popovic, Marta; Zaja, Roko; Fent, Karl; Smital, Tvrtko

    2013-11-22

    The organic anion-transporting polypeptide (OATP/Oatp) superfamily includes a group of polyspecific transporters that mediate transport of large amphipathic, mostly anionic molecules across cell membranes of eukaryotes. OATPs/Oatps are involved in the disposition and elimination of numerous physiological and foreign compounds. However, in non-mammalian species, the functional properties of Oatps remain unknown. We aimed to elucidate the role of Oatp1d1 in zebrafish to gain insights into the functional and structural evolution of the OATP1/Oatp1 superfamily. We show that diversification of the OATP1/Oatp1 family occurs after the emergence of jawed fish and that the OATP1A/Oatp1a and OATP1B/Oatp1b subfamilies appeared at the root of tetrapods. The Oatp1d subfamily emerged in teleosts and is absent in tetrapods. The zebrafish Oatp1d1 is similar to mammalian OATP1A/Oatp1a and OATP1B/Oatp1b members, with the main physiological role in transport and balance of steroid hormones. Oatp1d1 activity is dependent upon pH gradient, which could indicate bicarbonate exchange as a mode of transport. Our analysis of evolutionary conservation and structural properties revealed that (i) His-79 in intracellular loop 3 is conserved within OATP1/Oatp1 family and is crucial for the transport activity; (ii) N-glycosylation impacts membrane targeting and is conserved within the OATP1/Oatp1 family with Asn-122, Asn-133, Asn-499, and Asn-512 residues involved; (iii) the evolutionarily conserved cholesterol recognition interaction amino acid consensus motif is important for membrane localization; and (iv) Oatp1d1 is present in dimeric and possibly oligomeric form in the cell membrane. In conclusion, we describe the first detailed characterization of a new Oatp transporter in zebrafish, offering important insights into the functional evolution of the OATP1/Oatp1 family and the physiological role of Oatp1d1.

  12. IgM-Enriched Immunoglobulin Attenuates Systemic Endotoxin Activity in Early Severe Sepsis: A Before-After Cohort Study

    Science.gov (United States)

    Kirbach, Christin; Warszawska, Joanna; Meybohm, Patrick; Zacharowski, Kai; Koch, Alexander

    2016-01-01

    Introduction Sepsis remains associated with a high mortality rate. Endotoxin has been shown to influence viscoelastic coagulation parameters, thus suggesting a link between endotoxin levels and the altered coagulation phenotype in septic patients. This study evaluated the effects of systemic polyspecific IgM-enriched immunoglobulin (IgM-IVIg) (Pentaglobin® [Biotest, Dreieich, Germany]) on endotoxin activity (EA), inflammatory markers, viscoelastic and conventional coagulation parameters. Methods Patients with severe sepsis were identified by daily screening in a tertiary, academic, surgical ICU. After the inclusion of 15 patients, the application of IgM-IVIg (5 mg/kg/d over three days) was integrated into the unit’s standard operation procedure (SOP) to treat patients with severe sepsis, thereby generating “control” and “IgM-IVIg” groups. EA assays, thrombelastometry (ROTEM®) and impedance aggregometry (Multiplate®) were performed on whole blood. Furthermore, routine laboratory parameters were determined according to unit’s standards. Results Data from 26 patients were included. On day 1, EA was significantly decreased in the IgM-IVIg group following 6 and 12 hours of treatment (0.51 ±0.06 vs. 0.26 ±0.07, p<0.05 and 0.51 ±0.06 vs. 0.25 ±0.04, p<0.05) and differed significantly compared with the control group following 6 hours of treatment (0.26 ±0.07 vs. 0.43 ±0.07, p<0.05). The platelet count was significantly higher in the IgM-IVIg group following four days of IgM-IVIg treatment (200/nl ±43 vs. 87/nl ±20, p<0.05). The fibrinogen concentration was significantly lower in the control group on day 2 (311 mg/dl ±37 vs. 475 mg/dl ±47 (p = 0.015)) and day 4 (307 mg/dl ±35 vs. 420 mg/dl ±16 (p = 0.017)). No differences in thrombelastometric or aggregometric measurements, or inflammatory markers (interleukin-6 (IL-6), leukocyte, lipopolysaccharide binding protein (LBP)) were observed. Conclusion Treatment with IgM-enriched immunoglobulin

  13. Generation of Long-Lived Bone Marrow Plasma Cells Secreting Antibodies Specific for the HIV-1 gp41 Membrane-Proximal External Region in the Absence of Polyreactivity

    Science.gov (United States)

    Donius, Luke R.; Cheng, Yuxing; Choi, Jaewon; Sun, Zhen-Yu J.; Hanson, Melissa; Zhang, Michael; Gierahn, Todd M.; Marquez, Susanna; Uduman, Mohammed; Kleinstein, Steven H.; Irvine, Darrell; Love, J. Christopher; Reinherz, Ellis L.

    2016-01-01

    their fine specificities require a structural fitness of the antibody combining site involving heavy and light chain variable domains shaped by somatic hypermutation and affinity maturation of B cells in the germinal center. Perhaps more importantly, our results demonstrate that the majority of MPER-specific antibodies are not inherently polyspecific and/or autoreactive, suggesting that polyreactivity of MPER-specific antibodies is separable from their antigen specificity. PMID:27466419

  14. Effects of the glial cell line-derived neurotrophic factor family on chronic constrictive injury in rats%胶质细胞源性神经营养因子家族在大鼠坐骨神经慢性压榨损伤中的作用

    Institute of Scientific and Technical Information of China (English)

    胡玉萍; 杨建军; 李伟彦; 稽晴

    2011-01-01

    目的 研究大鼠坐骨神经慢性压榨损伤(chronic constrictive injury,CCI)中胶质细胞源性神经营养因子(glialcell line-derived neurotrophic factor,GDNF)和神经细胞黏附分子(neural cell adhesion molecule,NCAM)表达的变化,以及鞘内注射NCAM相似肽c3d、NCAM反义寡核甘酸(Anti)对神经病理性疼痛(neuropathic pain,NP)的影响,探讨GDNF、NCAM在NP中的作用及可能机制. 方法 实验1:成年雄性SD大鼠42只,随机分为2组(每组21只):疼痛组和对照组.疼痛组大鼠行左侧坐骨神经结扎术,建立CCI模型,对照组行假手术.分别于术前1d和术后1、3、5、7、14、21d测机械痛阈(mechanicalwithdrawl threshold,MWT)和热痛阈(thermal withdrawal latency,TWL).采用免疫组织化学染色和RT-PCR技术检测背根神经节(dorsal root ganglion,DRG)中GDNF和NCAM的表达变化.实验2:成年雄性SD大鼠24只,随机分为4组(每组6只):生理盐水(normal saline,NS)对照组、NS+ GDNF组、c3d+GDNF组、Anti-NCAM+ GDNF组.各组大鼠于建立CCI模型后3d鞘内注射上述制剂,观察其痛阈变化. 结果 实验1:与对照组相比,疼痛组大鼠术前1d、术后1、21 d MWT和TWL差异无统计学意义(P>0.05);术后3、5、7、14d MWT和TWL均降低,其中术后7d阈值最低(P<0.01);术后3、5、7、14d GDNF和NCAM的表达均升高,其中7d表达最高(P<0.01).实验2:与NS对照组相比,NS+ GDNF组、c3d+ GDNF组MWT和TWL明显降低(P<0.01),Anti-NCAM+ GDNF组差异无统计学意义(P>0.05);NS+ GDNF组、c3d+ GDNF组与给药前相比,MWT和TWL明显降低(P<0.01);Anti-NCAM+ GDNF组差异无统计学意义(P>0.05). 结论 大鼠CCI后出现痛阈下降,DRG中GDNF和NCAM表达增高;外源性GDNF可缓解NP,阻断NCAM表达可消减GDNF的镇痛作用,提示GDNF和NCAM信号通路参与了NP的发生和调节.%Objective The present study was to investigate the changes in the expressions of the glial cell line-derived neuro-trophic factor (GDNF) and

  15. Diagnóstico laboratorial da anemia hemolítica auto-imune: características do teste manual direto do PolybreneÒ Laboratory diagnosis of auto-immune hemolytic anemia: characteristics of the manual direct test of PolybreneTM

    Directory of Open Access Journals (Sweden)

    G.W. Braga

    1998-03-01

    Full Text Available O teste manual direto do PolybreneÒ (TDP e o teste de Coombs direto (TCD foram utilizados para a detecção de IgG na superfície de hemácias de pacientes com diagnóstico clínico e laboratorial de anemia hemolítica auto-imune (AHAI. OBJETIVO: Comparar a sensibilidade e especificidade do TPD e do TCD no diagnóstico da AHAI. MÉTODO: Foram estudados 18 pacientes com diagnóstico clínico-laboratorial de AHAI. Como indivíduos controles, foram testados 20 doadores de sangue assintomáticos e 20 pacientes com anemia falciforme. RESULTADOS: O TCD foi positivo em 14 pacientes e negativo em quatro indivíduos, enquanto o TDP foi positivo em 17 pacientes e negativo em um indivíduo que apresentava TCD positivo devido a fixação de complemento (C3d nas hemácias. Todos os eluatos positivos realizados com a técnica de diclorometano revelaram anticorpos quentes com especificidade "anti-Rh". A sensibilidade do TDP (94% para detectar fixação de IgG in vivo foi significantemente maior (pThe direct manual PolybreneTM test (DPT and the direct antiglobulin tests (DAT were employed to detect antibody sensitizing red blood cell (RCB in patients with clinical and laboratorial findings of autoimmune hemolytic anemia (AIHA. PURPOSE: To compare the sensitivity and specificity of DPT and DAT in the diagnosis of AIHA. METHODS: Eighteen consecutive patients with diagnosis of AIHA were evaluated. The control group consisted of 20 normal volunteers blood donors and 20 patients with sickle cell anemia. All patients and controls were submitted to DPT and DAT. All DAT positive samples were further tested using monospecific reagents ( anti-IgG heavy chain and anti-C3d. Positive samples for either DPT or DAT were evaluated by eluate technique using. The dichloromethane (DCM. RESULTS: The DAT was positive in 14 patients and negative in 4 subjects, while the DPT was positive in 17 patients and negative in 1 individual who had a positive DAT owing to complement (C3d. All

  16. Herpes simplex virus glycoprotein C: molecular mimicry of complement regulatory proteins by a viral protein.

    Science.gov (United States)

    Huemer, H P; Wang, Y; Garred, P; Koistinen, V; Oppermann, S

    1993-08-01

    Herpes simplex virus (HSV) encodes a protein, glycoprotein C (gC), which binds to the third complement component, the central mediator of complement activation. In this study the structural and functional relationships of gC from HSV type 1 (HSV-1) and known human complement regulatory proteins factor H, properdin, factor B, complement receptor 1 (CR1) and 2 (CR2) were investigated. The interaction of gC with C3b was studied using purified complement components, synthetic peptides, antisera against different C3 fragments and anti-C3 monoclonal antibodies (mAb) with known inhibitory effects on C3-ligand interactions. All the mAb that inhibited gC/C3b interactions, in a differential manner, also prevented binding of C3 fragments to factors H, B, CR1 or CR2. No blocking was observed with synthetic peptides representing different C3 regions or with factor B and C3d, whereas C3b, C3c and factor H were inhibitory, as well as purified gC. There was no binding of gC to cobra venom factor (CVF), a C3c-like fragment derived from cobra gland. Purified gC bound to iC3, iC3b and C3c, but failed to bind to C3d. Glycoprotein C bound only weakly to iC3 derived from bovine and porcine plasma, thus indicating a preference of the viral protein for the appropriate host. Binding of gC was also observed to proteolytic C3 fragments, especially to the beta-chain, thus suggesting the importance of the C3 region as a binding site. Purified gC from HSV-1, but not HSV-2, inhibited the binding of factor H and properdin but not of CR1 to C3b. The binding of iC3b to CR2, a molecule involved in B-cell activation and binding of the Epstein-Barr virus, was also inhibited by the HSV-1 protein. As factor H and properdin, the binding of which was inhibited by gC, are important regulators of the alternative complement pathway, these data further support a role of gC in the evasion of HSV from a major first-line host defence mechanism, i.e. the complement system. In addition, the inhibition of the C3/CR

  17. Identification of an additional class of C3-binding membrane proteins of human peripheral blood leukocytes and cell lines.

    Science.gov (United States)

    Cole, J L; Housley, G A; Dykman, T R; MacDermott, R P; Atkinson, J P

    1985-02-01

    Proteins binding the third component of complement (C3) were isolated by affinity chromatography from surface-labeled solubilized membranes of human peripheral blood cells and cell lines. The isolated molecules were subjected to NaDodSO4/PAGE, and autoradiographs of these gels indicated that C3-binding proteins could be divided into three groups based on Mr: (i) gp200, an approximately 200,000 Mr molecule previously identified as the C3b/C4b receptor or CR1; (ii) gp140, an approximately 140,000 Mr molecule previously identified as the C3d receptor or CR2; and (iii) gp45-70, a heretofore unrecognized group of 45,000-70,000 Mr C3-binding molecules. The cell distribution, Mr, antigenic cross-reactivity, and specificity of gp45-70 were examined. Erythrocytes have no detectable gp45-70, but all leukocyte populations examined possess this group of molecules. On neutrophils and mononuclear phagocytes, CR1 is the predominant C3-binding glycoprotein, but gp45-70 is present on both cell populations and on macrophage and neutrophil cell lines. B plus null cells, chronic lymphocytic leukemia cells, and an Epstein-Barr virus-transformed B-cell line possess CR1, CR2, and gp45-70. On T cells and T-cell lines gp45-70 is the predominant or, in some cases, the only C3-binding protein isolated. gp45-70 is structurally characterized as a broad band or doublet with a mean Mr that is slightly different for each cell population. gp45-70 binds iC3, C3b, and C4b, but not C3d, indicating that the binding region is probably within the C3c portion of C3b. A polyclonal antibody to CR1 and monoclonal antibodies to CR1 and CR2 do not immunoprecipitate gp45-70. While gp45-70 has not been previously characterized on human cells, a C3b-binding glycoprotein of similar Mr is present on rabbit alveolar macrophages. We conclude that gp45-70 is an additional group of membrane proteins present on human leukocytes that possess ligand-binding activity for C3b. PMID:3871945

  18. Curso clínico da anemia hemolítica auto-imune: um estudo descritivo Clinical course of autoimmune hemolytic anemia: an observational study

    Directory of Open Access Journals (Sweden)

    Maria Christina L. A. Oliveira

    2006-02-01

    identify the clinical, immunological and outcome characteristics of autoimmune hemolytic anemia patients treated at the (HC-UFMG Pediatric Hematology Unit and the Hemocentro de Belo Horizonte. METHODS: We evaluated 17 patients younger than 15 years old admitted from 1988 to 2003 were evaluated. Autoimmune hemolytic anemia diagnosis was based on the presence of acquired hemolysis and confirmed by positive direct Coombs polyspecific test results. Clinical, laboratory, and outcome data were obtained from patient records. RESULTS: The median age at diagnosis was 10.5 months. The direct Coombs polyspecific test was positive in 13 and negative in four patients. Monospecific testing was performed for 14 patients. The most frequent red cell autoantibody was IgG (five patients, followed by IgM in two. Thirteen patients had severe anemia and needed blood transfusions. Underlying diseases were identified in four patients: systemic lupus erythematosus, Hodgkin's lymphoma, autoimmune hepatitis and Langerhans cell histiocytosis. The remaining patients were classified as having primary disease. The median follow-up period was 11 months (5 to 23 months. Three children died, two after splenectomy and one with complications of the underlying disease. CONCLUSION: Autoimmune hemolytic anemia is rare in children and adolescents. Although patients usually respond to corticosteroids and/or immunoglobulin, fatal cases can occur. Prognosis is worse in patients with chronic underlying diseases.

  19. The Biomarker Changes of a Heavy Fuel Oil After Different Weathering Times

    Institute of Scientific and Technical Information of China (English)

    MA Qimin; NI Zhanglin; YU Zhigang

    2009-01-01

    This paper presents the experimental results of composition changes of heavy fuel oil by simulating weathering in static seawater under natural environmental conditions. The results indicate: n-C10 to n-C15 were lost gradually in 24 weeks and the relative abundance of alkanes with long chains (n-C19) increased markedly. The aromatic compounds with less than two rings (except C4N) were completely lost in 24 weeks and CnP and CnD became the main aromatics in the heavy fuel oil after 24 weeks. The ratios of n-C17/Pristane (Pr) and n-C18/Phytane (Ph) were suitable for identifying lightly weathered (3 weeks) heavy fuel oil. The ratios of n-C17/n-C18 and Pr/Ph were suitable for identifying moderately weathered heavy fuel oil (12 weeks); the ratios of C2D/C2P and C3D/C3P did not change significantly in 24 weeks and were more suitable for identifying moderately weathered heavy fuel oil (24 weeks).

  20. Relation of anomalous resistivity and current intensity in turbulent collisionless plasma cascades in the geospace

    Science.gov (United States)

    Lapenta, Giovanni; Kemel, Koen; Henri, Pierre; Califano, Francesco; Markidis, Stefano

    2015-11-01

    Using the full kinetic implicit PIC code, iPiC3D, we studied the properties of plasma kinetic turbulence, such as would be found at the interface between the solar wind and the Earth magnetosphere at low latitude during northwards periods. In this case, in the presence of a magnetic field oriented mostly perpendicular to the velocity shear, turbulence is fed by the disruption of a Kelvin-Helmholtz vortex chain via secondary instabilities, vortex pairing and non-linear interactions. We found that the magnetic energy spectral cascade between ion and electron inertial scales is in agreement with satellite observations and previous numerical simulations; however, in our case the spectrum ends with a peak beyond de due to the occurrence of the lower hybrid drift instability. The electric energy spectrum is influenced by secondary instabilities: anomalous resistivity, fed by the development of the lower hybrid drift instability, steepens the spectral decay and, depending on the alignment of B and the shear vorticity, peaks due to ion-Bernstein waves may dominate the spectrum around di. A key conclusion of the study is that the anomalous resistivity produced by these complex wave and instabilities can indeed very accurately be described in terms of a proportionality with the current. This research used resources of NERSC, a DOE Office of Science User Facility supported by the Office of Science of the U.S. DOE under Contract No. DE-AC02-05CH11231.

  1. The cationic peptide LL-37 binds Mac-1 (CD11b/CD18) with a low dissociation rate and promotes phagocytosis.

    Science.gov (United States)

    Zhang, Xianwei; Bajic, Goran; Andersen, Gregers R; Christiansen, Stig Hill; Vorup-Jensen, Thomas

    2016-05-01

    As a broad-spectrum anti-microbial peptide, LL-37 plays an important role in the innate immune system. A series of previous reports implicates LL-37 as an activator of various cell surface receptor-mediated functions, including chemotaxis in integrin CD11b/CD18 (Mac-1)-expressing cells. However, evidence is scarce concerning the direct binding of LL-37 to these receptors and investigations on the associated binding kinetics is lacking. Mac-1, a member of the β2 integrin family, is mainly expressed in myeloid leukocytes. Its critical functions include phagocytosis of complement-opsonized pathogens. Here, we report on interactions of LL-37 and its fragment FK-13 with the ligand-binding domain of Mac-1, the α-chain I domain. LL-37 bound the I-domain with an affinity comparable to the complement fragment C3d, one of the strongest known ligands for Mac-1. In cell adhesion assays both LL-37 and FK-13 supported binding by Mac-1 expressing cells, however, with LL-37-coupled surfaces supporting stronger cell adhesion than FK-13. Likewise, in phagocytosis assays with primary human monocytes both LL-37 and FK-13 enhanced uptake of particles coupled with these ligands but with a tendency towards a stronger uptake by LL-37.

  2. A CD21 low phenotype, with no evidence of autoantibodies to complement proteins, is consistent with a poor prognosis in CLL.

    Science.gov (United States)

    Nichols, Eva-Maria; Jones, Rachel; Watson, Rachael; Pepper, Chris J; Fegan, Chris; Marchbank, Kevin J

    2015-10-20

    B-cell chronic lymphocytic leukemia (CLL) is characterized by differential BCR signaling and autoimmune complications. Complement modulates B-cell function via C3d and CD21 cross-linked to the B-cell receptor (BCR). We hypothesized that CD21 contributes to BCR signaling and participates in the autoimmunity associated with CLL. We analyzed CD21 expression on 106 CLL patient samples and matched serum from 50 patients for the presence of soluble CD21 and autoantibodies to CR2, CR1, MCP and FH. CD21 expression on CLL B-cells was significantly lower than that expressed on B-cells from age-matched controls (P < 0.0001) and was inversely correlated with soluble CD21 (r2 = -0.41). We found no evidence of autoantibody to any complement regulator. Low CD21 expression correlated to prognostic subsets of CLL patients, i.e. cases with unmutated IGHV genes (P = 0.0006), high CD38 (P = 0.02) and high ZAP70 expression (P = 0.0017). Low CD21 expression was inversely correlated to the levels of phosphotyrosine induced in CLL cells following BCR ligation with αIgM (r2 = -0.21). Importantly, lower CD21 expression was also predictive for reduced overall survival (P = 0.005; HR = 2.7). In conclusion, we showed that reduced expression of CD21 on CLL B-cells appears functionally relevant and was associated with poor clinical outcomes. PMID:26452134

  3. Dosimetry of cone beam computed tomography scanning for diagnosis and planning in implant dentistry

    Energy Technology Data Exchange (ETDEWEB)

    Santos Pinto de A, E. L.; Manzi, F. R.; Goncalves Z, E. [Pontifical Catholic University of Minas Gerais, Av. Jose Gaspar 500, 30535-901 Belo Horizonte, Minas Gerais (Brazil); Nogueira, M. S.; Fernandes Z, M. A., E-mail: madelon@cdtn.br [Development Center of Nuclear Technology / CNEN, Av. Pte. Antonio Carlos 6627, 31270-901Belo Horizonte, Minas Gerais (Brazil)

    2015-10-15

    Full text: The radiation dose and estimate the radiation induced risk of cancer and morpho functional alterations according to BEIR VII (2006) and recommendations of the ICRP 103 (2007) were measured in cone beam computed tomography (CBCT) scanning (Tc Kodak 9000C 3D) in different oral and maxillofacial regions for diagnosis and planning in implant dentistry for each examination protocol: jaw full, maxilla full and jaw and maxilla full associated. Thermoluminescent dosimeters (TLD- 100 H) were placed in an Alderson-Rando in regions corresponding to the crystalline, parotid, submandibular and thyroid glands and ovaries. The highest values for entrance skin dose were observed in the region of the parotid and submandibular glands, 9.612 mGy to 7.912 mGy and 8.818 mGy to 0.483 mGy, respectively. All examination protocols presented on the right and left sides in the region of the submandibular gland the highest values for absorbed dose (D). In the jaw full exam the thyroid glands on both sides presented highest dose values than maxilla full exam. This study allowed measuring the entrance skin dose and the absorbed dose (D) highlighting a dosimetric preponderance to the salivary glands. With danger of to radiation that induces cancer risk was observed that the age group most likely to have to risk of cancer was 20 years, compared to 30, 40, 50, 60,70 and 80 years. (Author)

  4. Mechanisms of Host-Pathogen Protein Complex Formation and Bacterial Immune Evasion of Streptococcus suis Protein Fhb.

    Science.gov (United States)

    Li, Xueqin; Liu, Peng; Gan, Shuzhen; Zhang, Chunmao; Zheng, Yuling; Jiang, Yongqiang; Yuan, Yuan

    2016-08-12

    Streptococcus suis serotype 2 (S. suis 2)-induced sepsis and meningitis are often accompanied by bacteremia. The evasion of polymorphonuclear leukocyte-mediated phagocytic clearance is central to the establishment of bacteremia caused by S. suis 2 and is facilitated by the ability of factor H (FH)-binding protein (Fhb) to bind FH on the bacterial surface, thereby impeding alternative pathway complement activation and phagocytic clearance. Here, C3b/C3d was found to bind to Fhb, along with FH, forming a large immune complex. The formation of this immune complex was mediated by domain II of Fhb via electrostatic and hydrophobic interactions, which, to our knowledge, is a new type of interaction. Interestingly, Fhb was found to be associated with the cell envelope and also present in the culture supernatant, where secreted Fhb inhibited complement activation via interactions with domain II, thereby enhancing antiphagocytic clearance by polymorphonuclear leukocytes. Thus, Fhb is a multifunctional bacterial protein, which binds host complement component C3 as well as FH and interferes with innate immune recognition in a secret protein manner. S. suis 2 therefore appears to have developed a new strategy to combat host innate immunity and enhance survival in host blood. PMID:27342778

  5. Structure, morphology, and aging of Ag-Fe dumbbell nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Elsukova, Anna; Li, Zi-An; Moeller, Christina; Spasova, Marina; Acet, Mehmet; Farle, Michael [Experimentalphysik (AG Farle) and CENIDE, Universitaet Duisburg-Essen, Duisburg (Germany); Kawasaki, Masahiro [Jeol Inc., Peabody, MA (United States); Ercius, Peter; Duden, Thomas [National Center for Electron Microscopy, Lawrence Berkeley National Laboratory, CA (United States)

    2011-10-15

    Dumbbell-shaped or Janus-type nanocomposites provide multifunctional properties with various diagnostic and therapeutic applications in biomedicine. We have prepared dumbbell Ag-Fe nanoparticles by magnetron sputtering with subsequent in-flight annealing. Structural properties and chemical compositions of freshly prepared and 5-month aged particles were examined by means of transmission electron microscopy including high-resolution imaging, energy dispersive X-ray spectroscopy, and 3D electron tomography. Fresh particles consist of a faceted Ag part on a Fe-Fe{sub 3}O{sub 4} composite particle of more spherical shape. Aging changes the crystallinity and morphology of the particles. The aged nanocomposite consists of a silver spherical particle that is attached to a hollow iron oxide sphere containing one or several silver clusters inside. TEM images of the fresh (a) and aged (b) Ag-Fe nanoparticles. (c) 3D reconstructed image of an aged Ag-Fe particle with color segmentation. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  6. Ectopic Germinal Centers and IgG4-Producing Plasmacytes Observed in Synovia of HLA-B27+ Ankylosing Spondylitis Patients with Advanced Hip Involvement

    Directory of Open Access Journals (Sweden)

    Xiugao Feng

    2015-01-01

    Full Text Available Introduction. Ectopic lymphoid neogenesis and the presence of IgG4-positive plasmacytes have been confirmed in chronic inflammatory sclerosing diseases. This study aims to investigate hip synovial tissues of ankylosing spondylitis (AS patients for IgG4-positive plasma cells and ectopic lymphoid tissues with germinal centers (GCs. Methods. Synovial samples were collected from 7 AS patients who received total hip replacement and were evaluated using immunohistochemistry for the presence of CD20+ B-cells, CD3+ T-cells, CD21+ follicular dendritic cells (FDC, and CD38+ plasma cells. Furthermore, immunoglobulin G (IgG and IgG4, IgA, IgM, and complement components C3d and C4d in synovia were evaluated. Both synovial CD21+ FDCs and IgG4-producing plasmacytes were analyzed. Results. All seven patients had severe fibrosis. Massive infiltrations of lymphocytes were found in 5 out of 7 patients’ synovia. Ectopic lymphoid tissues with CD21+ FDC networks and IgG4-positive plasma cells were observed coincidentally in two patients’ synovia. Conclusion. The pathophysiological mechanism of AS patients’ hip damage might be related to the coincidental presence of ectopic lymphoid tissue with FDCs network and IgG4-positive plasma cells identified here for the first time in AS patients’ inflamed synovial tissue.

  7. Detection of Salmonella invA gene in shrimp enrichment culture by polymerase chain reaction.

    Science.gov (United States)

    Upadhyay, Bishnu Prasad; Utrarachkij, Fuangfa; Thongshoob, Jarinee; Mahakunkijcharoen, Yuvadee; Wongchinda, Niracha; Suthienkul, Orasa; Khusmith, Srisin

    2010-03-01

    Contamination of seafood with salmonellae is a major public health concern. Detection of Salmonella by standard culture methods is time consuming. In this study, an enrichment culture step prior to polymerase chain reaction (PCR) was applied to detect 284 bp fragment of Salmonella invA in comparison with the conventional culture method in 100 shrimp samples collected from four different shrimp farms and fresh food markets around Bangkok. Samples were pre-enriched in non-selective lactose broth (LB) and selective tetrathionate broth (TTB). PCR detection limit was 10 pg and 10(4) cfu/ml of viable salmonellae with 100% specificity. PCR assay detected 19 different Salmonella serovars belonging to 8 serogroups (B, C1, C2-C3, D1, E1, E4 and K) commonly found in clinical and environmental samples in Thailand. The detection rate of PCR following TTB enrichment (24%) was higher than conventional culture method (19%). PCR following TTB, but not in LB enrichment allowed salmonella detection with 84% sensitivity, 90% specificity and 89% accuracy. Shrimp samples collected from fresh food markets had higher levels of contaminated salmonellae than those from shrimp farms. The results indicated that incorporation of an enrichment step prior to PCR has the potential to be applied for detection of naturally contaminated salmonellae in food, environment and clinical samples.

  8. Design and synthesis of γ-butyrolactone derivatives as potential spermicidal agents.

    Science.gov (United States)

    Pandey, Rishi Ranjan; Srivastava, Akansha; Pachauri, Shakti Deep; Khandelwal, Kiran; Naqvi, Arshi; Malasoni, Richa; Kushwaha, Bhavana; Kumar, Lokesh; Maikhuri, Jagdamba Prasad; Pandey, Garima; Paliwal, Sarvesh; Gupta, Gopal; Dwivedi, Anil Kumar

    2014-08-15

    A series of γ-butyrolactone derivatives has been designed and synthesized from commercially available 2-acetyl butyrolactone (3-acetyldihydrofuran-2(3H)-one, 1) by aminoalkylating its active methylene followed by condensation with different aldehydes. Compounds having amino group were further converted to their respective tartrate salts and were evaluated for spermicidal activity against human sperm in vitro. Compounds showing appreciable spermicidal activity at ⩽0.5% [3c, 4d (0.5%); 2c, 3d (0.1%); 2d, 4c (0.05%)] were tested for safety studies against human cervical (HeLa) cell line. These compounds were found safer than, Nonoxynol-9. One of the two most active compounds was also found to be the safest (IC50=961 μg/ml; 4c), while the second compound exhibited lower safety against HeLa (IC50=269 μg/ml; 2d). The compound 4c significantly reduced the number of free thiols on human sperm. All the compounds were inactive against Trichomonas vaginalis. PMID:25027939

  9. Approximation of Convex Bodies by Convex Bodies%凸体间的逼近

    Institute of Scientific and Technical Information of China (English)

    国起; Sten Kaijser

    2003-01-01

    For the affine distance d(C,D)between two convex bodies C,D(∈)Rn,which reduces to the Banach-Mazur distance for symmetric convex bodies, the bounds of d(C,D)have been studied for many years. Some well known estimates for the upper-bounds are as follows: F. John proved d(C,D)≤n1/2 if one is an ellipsoid and another is symmetric,d(C,D)≤n if both are symmetric, and fromF. John's result and d(C1,C2)≤d(C1,C3)d(C2,C3) one has d(C,D)≤n2 for general convex bodies;M.Lassak proved d(C,D)≤(2n-1) if one of them is symmetric.In this paper we get an estimate which includes all the results above as special cases and refines some of them in terms of measures of asymmetry for convex bodies.

  10. A Rare Case; Hemolytic Disease of Newborn Associated with Anti-jkb

    Directory of Open Access Journals (Sweden)

    İlknur Tolunay

    2015-08-01

    Full Text Available Jka and Jkb antibodies (Kidd blood group system can cause acute and delayed type transfusion reactions as well as hemolytic disease of newborn. Jka and Jkb antibodies are seen after events like blood transfusions, pregnancy, abortion and curettage. Hemolytic disease of newborn related to Kidd-Jkb incompatibility is rare and mostly has a good prognosis. The patient was consulted to our department because of 20 hours of jaundice after birth. He was treated with intensive phototherapy due to the high level of total-value bilirubin (17,6 mg/dl. Mother and patient were both B Rh (+. After direct coombs IgG +++ and C3d ++ values, further investigations were performed and mother had indirect coombs ++ and kidd antigen+. So, the newborn was diagnosed with hemolytic disease of newborn due to kidd incompatibility and was discharged on the fourth day of the treatment without sequel. In the literature serious cases are mentioned, mortality and disabilities are also seen. It is appropriate that pediatricians investigate the subgroup incompatibilities of newborns with hemolytic diseases without ABO and Rh incompatibility in early period, or those of newborns which are having a long respond concerning medical treatment.

  11. Microstructural Analysis and Micromechanical Modeling of Flow Behaviour of Dual Phase Steels Using a Representative Volume Element Method

    Science.gov (United States)

    Amirmaleki, Maedeh

    Micromechanical modeling of flow curves of DP500 and DP600 steels in uniaxial tension was carried out using the representative volume element (RVE) method. Digimat and ABAQUS software were coupled and used to provide the required RVE model parameters and to perform simulations. Modeling results were validated using the experimental flow curves of the steels. It was found that the flow curve of DP500 steel was accurately predicted from the onset of plastic deformation up to the onset of necking. In case of DP600 steel, the numerical flow curve accurately predicted the experimental flow curve of steel after 0.07 strain up to necking strain. The RVE size of 12.7x12.7x12.7 mum and 7.9x7.9x7.9 mum containing 26 martensite islands were found as the optimum RVE sizes for DP500 and DP600 steel, respectively. A mesh of C3D4 elements having a size of 0.050 mum was found to be the optimum element type and mesh size.

  12. DHMPIV and Tomo-PIV measurements of three-dimensional structures in a turbulent boundary layer

    Science.gov (United States)

    Amili, O.; Atkinson, C.; Soria, J.

    In turbulent boundary layers, a large portion of total turbulence production happens in the near wall region, y/δ Tomo-PIV) was used to extract the 3C-3D velocity field using a rapid and less memory intensive reconstruction algorithm. It is based on a multiplicative line-of-sight (MLOS) estimation that determines possible particle locations in the volume, followed by simultaneous iterative correction. Application of MLOS-SART and MART to a turbulent boundary layer at Refθ=2200 using a 4 camera Tomo-PIV system with a volume of 1000×1000×160 voxels is discussed. In addition, near wall velocity measurement attempt made by digital holographic microscopic particle image velocimetry (DHMPIV). The technique provides a solution to overcome the poor axial accuracy and the low spatial resolution which are common problems in digital holography [5]. By reducing the depth of focus by at least one order of magnitude as well as increasing the lateral spatial resolution, DHMPIV provides the opportunity to resolve the small-scale structures existing in near wall layers.

  13. Production of resistant starch by extrusion cooking of acid-modified normal-maize starch.

    Science.gov (United States)

    Hasjim, Jovin; Jane, Jay-Lin

    2009-09-01

    The objective of this study was to utilize extrusion cooking and hydrothermal treatment to produce resistant starch (RS) as an economical alternative to a batch-cooking process. A hydrothermal treatment (110 degrees C, 3 d) of batch-cooked and extruded starch samples facilitated propagation of heat-stable starch crystallites and increased the RS contents from 2.1% to 7.7% up to 17.4% determined using AOAC Method 991.43 for total dietary fiber. When starch samples were batch cooked and hydrothermally treated at a moisture content below 70%, acid-modified normal-maize starch (AMMS) produced a greater RS content than did native normal-maize starch (NMS). This was attributed to the partially hydrolyzed, smaller molecules in the AMMS, which had greater mobility and freedom than the larger molecules in the NMS. The RS contents of the batch-cooked and extruded AMMS products after the hydrothermal treatment were similar. A freezing treatment of the AMMS samples at -20 degrees C prior to the hydrothermal treatment did not increase the RS content. The DSC thermograms and the X-ray diffractograms showed that retrograded amylose and crystalline starch-lipid complex, which had melting temperatures above 100 degrees C, accounted for the RS contents.

  14. Green synthesis of novel quinoline based imidazole derivatives and evaluation of their antimicrobial activity

    Directory of Open Access Journals (Sweden)

    N.C. Desai

    2014-12-01

    Full Text Available We have described the conventional and microwave method for the synthesis of N-(4-((2-chloroquinolin-3-ylmethylene-5-oxo-2-phenyl-4,5-dihydro-1H-imidazol-1-yl(arylamides 3a–l. It is observed that the solvent-free microwave thermolysis is a convenient, rapid, high-yielding, and environmental friendly protocol for the synthesis of quinoline based imidazole derivatives when compared with conventional reaction in a solution phase. Antimicrobial activity of the newly synthesized compounds is screened in vitro on the following microbial cultures: Escherichia coli (MTCC 443, Pseudomonas aeruginosa (MTCC 1688, Staphylococcus aureus (MTCC 96, Streptococcus pyogenes (MTCC 442, Candida albicans (MTCC 227, Aspergillus niger (MTCC 282, Aspergillus clavatus (MTCC 1323. All the synthesized bio-active molecules are tested for their in vitro antimicrobial activity by bioassay namely serial broth dilution. Among these compounds 3c, 3d, 3f, 3h and 3j show significant potency against different microbial strains. All the compounds have been characterized by IR, 1H NMR, 13C NMR and mass spectral data. On the basis of statistical analysis, it is observed that these compounds give significant co-relation.

  15. Visualization of 3D Geological Models on Google Earth

    Science.gov (United States)

    Choi, Y.; Um, J.; Park, M.

    2013-05-01

    Google Earth combines satellite imagery, aerial photography, thematic maps and various data sets to make a three-dimensional (3D) interactive image of the world. Currently, Google Earth is a popular visualization tool in a variety of fields and plays an increasingly important role not only for private users in daily life, but also for scientists, practitioners, policymakers and stakeholders in research and application. In this study, a method to visualize 3D geological models on Google Earth is presented. COLLAborative Design Activity (COLLADA, an open standard XML schema for establishing interactive 3D applications) was used to represent different 3D geological models such as borehole, fence section, surface-based 3D volume and 3D grid by triangle meshes (a set of triangles connected by their common edges or corners). In addition, we designed Keyhole Markup Language (KML, the XML-based scripting language of Google Earth) codes to import the COLLADA files into the 3D render window of Google Earth. The method was applied to the Grosmont formation in Alberta, Canada. The application showed that the combination of COLLADA and KML enables Google Earth to effectively visualize 3D geological structures and properties.; Visualization of the (a) boreholes, (b) fence sections, (c) 3D volume model and (d) 3D grid model of Grossmont formation on Google Earth

  16. Springback prediction of thick-walled high-strength titanium tube bending

    Institute of Scientific and Technical Information of China (English)

    Song Feifei; Yang He; Li Heng; Zhan Mei; Li Guangjun

    2013-01-01

    Significant springback occurs after tube rotary-draw-bending (RDB), especially for a high-strength Ti-3Al-2.5V tube (HSTT) due to its high ratio of yield strength to Young’s modulus. The combination scheme of explicit and implicit is preferred to predict the springback. This simu-lation strategy includes several numerical parameters, such as element type, number of elements through thickness (NEL), element size, etc. However, the influences of these parameters on spring-back prediction accuracy are not fully understood. Thus, taking the geometrical specification 9.525 mm · 0.508 mm of a HSTT as the objective, the effects of numerical parameters on prediction accuracy and computation efficiency of springback simulation of HSTT RDB are investigated. The simulated springback results are compared with experimental ones. The main results are:(1) solid and continuum-shell elements predict the experimental results well;(2) for C3D8R elements, NEL of at least 3 is required to obtain reliable results and a relative error of 29%can occur as NEL is varied in the range of 1-3;(3) specifying damping factor typically works well in Abaqus/Emplicit simula-tion of springback and the springback results are sensitive to the magnitude of damping factor. In addition, the explanations of the effect rules are given and a guideline is added.

  17. Influence Of Resonances On Spectral Formation Of X-Ray Lines In Fe XVII

    CERN Document Server

    Chen, G X; Chen, Guo-Xin; Pradhan, Anil K.

    2002-01-01

    New theoretical results from large-scale relativistic close coupling calculations reveal the precise effect of resonances in collisional excitation of x-ray lines of Ne-like Fe XVII. Employing the Breit-Pauli R-matrix method and a 89-level eigenfunction expansion including up to n = 4 levels shows significant resonance enhancement of the collision strengths of forbidden and intercombination transitions. The present results differ from all previous calculations, heretofore without detailed resonance structures, and should help resolve longstanding discrepancies. In particular, the present line ratios of three benchmark diagnostic lines 3C, 3D, and 3E at 15.014, 15.265, and 15.456 A respectively, are in excellent agreement with two independent measurements on Electron-Beam-Ion-Traps [Laming et al, Astrophys. J, 545, L161 (2000) and Brown et al, Astrophys. J, 502, 1015 (1998)]. The strong energy dependence due to resonances in these and other cross sections is demonstrated for the first time. It is of general im...

  18. Dyshidrotic eczema: relevance to the immune response in situ

    Directory of Open Access Journals (Sweden)

    Frank J. Pinto

    2009-08-01

    Full Text Available Context: Pompholyx (called dyshidrosis by some is one of the most common conditions and its immune response is presently poorly understood. Case report: We describe a 58 year old African American female with a clinical history of rheumatoid arthritis and type II diabetes who presented a chronic five-year, itchy vesicular/blistering rash involving her hands and feet. A lesional skin biopsy was taken for hematoxylin and eosin (H & E analysis. In addition, a multicolor direct immunofluorescence (MDIF and immunohistochemistry (IHC studies were performed. The major findings to be reported were: the H & E examination revealed spongiotic dermatitis and pompholix. IHC and MDIF studies demonstrated focally deposits of positive CD45, CD3, CD8, anti myeloperoxidase (MPO, and anti-human IgE, C3C, C3D and anti-human-fibrinogen within the epidermal spongiotic process, as well as around the blood vessels surrounding the inflammatory process especially at the sweat glands and respective ductus. The patient began mycophenolate mofetil therapy, with successful clearing of the palms and soles. Conclusion: The significance of our findings indicates a complex immunological process including complement, MPO and T-cell immune response. In addition, possibly a secondary allergic process for the presence of IgE immune response and possibly aggravation by application of other medicines. Further immunological studies on pompholyx are needed

  19. Dyshidrotic eczema: Relevance to the immune response in situ

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2009-01-01

    Full Text Available Context: Pompholyx (called dyshidrosis by some is one of the most common conditions and its immune response is presently poorly understood. Case report: We describe a 58 year old African American female with a clinical history of rheumatoid arthritis and type II diabetes who presented a chronic five-year, itchy vesicular/blistering rash involving her hands and feet. A lesional skin biopsy was taken for hematoxylin and eosin (H & E analysis. In addition, a multicolor direct immunofluorescence (MDIF and immunohistochemistry (IHC studies were performed. The major findings to be reported were: the H & E examination revealed spongiotic dermatitis and pompholix. IHC and MDIF studies demonstrated focally deposits of positive CD45, CD3, CD8, anti myeloperoxidase (MPO, and anti-human IgE, C3C, C3D and anti-human-fibrinogen within the epidermal spongiotic process, as well as around the blood vessels surrounding the inflammatory process especially at the sweat glands and respective ductus. The patient began mycophenolate mofetil therapy, with successful clearing of the palms and soles. Conclusion : The significance of our findings indicates a complex immunological process including complement, MPO and T-cell immune response. In addition, possibly a secondary allergic process for the presence of IgE immune response and possibly aggravation by application of other medicines. Further immunological studies on pompholyx are needed. (Abreu Velez AM, Pinto FJ, Howard MS.

  20. Synthesis and Evaluation of New 1,3,4-Thiadiazole Derivatives as Antinociceptive Agents.

    Science.gov (United States)

    Altıntop, Mehlika Dilek; Can, Özgür Devrim; Demir Özkay, Ümide; Kaplancıklı, Zafer Asım

    2016-01-01

    In the current work, new 1,3,4-thiadiazole derivatives were synthesized and investigated for their antinociceptive effects on nociceptive pathways of nervous system. The effects of these compounds against mechanical, thermal and chemical stimuli were evaluated by tail-clip, hot-plate and acetic acid-induced writhing tests, respectively. In addition, activity cage was performed to assess the locomotor activity of animals. The obtained data indicated that compounds 3b, 3c, 3d, 3e, 3g and 3h increased the reaction times of mice both in the hot-plate and tail-clip tests, indicating the centrally mediated antinociceptive activity of these compounds. Additionally, the number of writhing behavior was significantly decreased by the administration of compounds 3a, 3c, 3e and 3f, which pointed out the peripherally mediated antinociceptive activity induced by these four compounds. According to the activity cage tests, compounds 3a, 3c and 3f significantly decreased both horizontal and vertical locomotor activity of mice. Antinociceptive behavior of these three compounds may be non-specific and caused by possible sedative effect or motor impairments. PMID:27490523

  1. Alternative pathway of complement activation by stimulated T lymphocytes. II. Elevation of cytotoxic potential against complement receptor-carrying cell lines.

    Science.gov (United States)

    Ramos, O F; Sármay, G; Eggertsen, G; Nilsson, B; Klein, E; Gergely, J

    1987-07-01

    Exposure of lectin-stimulated (concanavalin A, phytohemagglutinin and pokeweed mitogen) blood lymphocytes to human serum or to purified C3 increased their cytotoxic capacity towards complement receptor positive targets such as Raji and Daudi cells. The lysis of complement receptor-negative lymphoblastoid cell lines was not influenced. The lytic capacity of lymphocytes exposed to 12-O-tetradecanoylphorbol 13-acetate was not elevated by human serum. Lectin-stimulated lymphocytes were previously shown to activate and bind C3. The results using lymphocytes activated in different ways and targets with or without complement receptor expression suggest that the C3b deposited on lymphocytes binds to the complement receptor on the targets. This contact elevates the avidity between the two cells as indicated also by the increased frequency of the lymphocyte-target conjugates. On the basis of immune adherence the C3 fragment bound on the lymphocytes was identified as C3b. The increase of the conjugate formation and cytotoxicity was abrogated when the target cells, Raji, were pre-exposed to purified C3d which occupy the CR2 receptor. The majority of lymphocytes responsible for the cytotoxicity were CD8+. PMID:3111863

  2. Role of Akata cell membrane fluidity in susceptibility to Epstein-Barr virus infection.

    Science.gov (United States)

    Pozzi, D; Lisi, A; Grimaldi, S

    1995-01-01

    Infection by Epstein-Barr virus (EBV), a B lymphotropic human herpesvirus, of its target cells is initiated by the binding of the viral envelope glycoprotein gp350/220 to a 145-kDa cell membrane glycoprotein (CD21, CR2) which also serves as the receptor for the complement fragment C3d (Fingeroth et al., 1984; Nemerow et al., 1987). We used the fluorescent probe 1-6-diphenyl-1,3,5-hexatriene (DPH), extremely sensitive to the polar environment, in order to analyse the membrane viscosity distribution in single cells of two lymphoid cell lines, Raji and Akata. Lipid analysis on both cell lines showed a slightly lower cholesterol:phospholipid molar ratio on Akata than on Raji cells. Measurements of cell fluidity by DPH polarization in native cells and after cholesterol enrichment indicated that the apparent Akata membrane viscosity was lower than the viscosity of Raji cells. To examine the possibility that this difference could be correlated to a difference in the behaviour of Akata and Raji cells in expressing EBV early antigens, both lines were superinfected with the EBV non-transforming P3HR1 strain. We report here evidence that lipid composition can regulate EBV entry into cells. PMID:8539494

  3. The mode of action of immunological adjuvants.

    Science.gov (United States)

    Allison, A C

    1998-01-01

    Adjuvants augment immune responses to antigens and influence the balance between cell-mediated and humoral responses, as well as the isotypes of antibodies formed. New adjuvant formulations include antigen-carrying vehicles and small molecules with immunomodulating activity. Widely used two-phase vehicles comprise liposomes and microfluidized squalene or squalane emulsions. These are believed to target antigens to antigen-presenting cells, including dendritic cells (DC), follicular dendritic cells (FDC) and B-lymphocytes. Activation of complement generates C3d, which binds CR2 (CD21) on FDC and B-lymphocytes, thereby stimulating the proliferation of the latter and the generation of B-memory. Targeting of antigens to DC may favour cell-mediated immunity. Immunomodulating agents induce the production of cytokine cascades. In a primary cascade at injection sites TNF-alpha, GM-CSF and IL-1 are produced. TNF-alpha promotes migration of DC to lymphoid tissues, while GM-CSF and IL-1 accelerate the maturation of DC into efficient antigen-presenting cells for T-lymphocytes. In a secondary cytokine cascade in draining lymph nodes, DC produce IL-12, which induces Th1 responses with the production of IFN-gamma. The cytokines elicit cell-mediated immune responses and the formation of antibodies of protective isotypes, such as IgG2a in the mouse and IgG1 in humans. Antibodies of these isotypes activate complement and collaborate with antibody-dependent effector cells in protective immune responses. PMID:9554254

  4. Solvothermal synthesis and high optical performance of three-dimensional sea-urchin-like TiO2

    International Nuclear Information System (INIS)

    Graphical abstract: I–V characteristics of different TiO2 microspheres based DSSCs (a) 3D sphere-like, (b) 3D flower-like, (c) 3D sea-urchin-like. - Highlights: • 3D sea-urchin-like TiO2 was synthesized by solvothermal method. • The effects of preparation parameters on the microstructure of the microspheres were investigated. • The photoelectric properties of 3D sea-urchin-like TiO2 were studied upon DSSCs. • The PCE of the 3D sea-urchin-like TiO2 was higher than that of other morphologies. - Abstract: Three-dimensional (3D) sea-urchin-like TiO2 microspheres were successfully synthesised by solvothermal method. The effects of preparation parameters including reaction temperature, concentration and mass fraction of precursor, and solvent volume on the microstructure of the microspheres were investigated. Results of scanning electron microscopy showed that the preparation parameters played a critical role in the morphology of 3D sea-urchin-like TiO2. In addition, when the sea-urchin-like TiO2 nanostructures were used as the dye-sensitized solar cells (DSSCs) anode, the power-conversion efficiency was higher than that of other morphologies, which was due to the special 3D hierarchical nanostructure, large specific surface area, and enhanced absorption of UV–vis of the TiO2 nanostructures

  5. Exploring Optimal Topology and Routing Algorithm for 3D Network on Chip

    Directory of Open Access Journals (Sweden)

    N. Viswanathan

    2012-01-01

    Full Text Available Problem statement: Network on Chip (NoC is an appropriate candidate to implement interconnections in SoCs. Increase in number of IP blocks in 2D NoC will lead to increase in chip area, global interconnect, length of the communication channel, number of hops transversed by a packet, latency and difficulty in clock distribution. 3D NoC is evolved to overcome the drawbacks of 2D NoC. Topology, switching mechanism and routing algorithm are major area of 3D NoC research. In this study, three topologies (3D-MT, 3D-ST and 3D-RNT and routing algorithm for 3D NoC are presented. Approach: Experiment is conducted to evaluate the performance of the topologies and routing algorithm. Evaluation parameters are latency, probability and network diameter and energy dissipation. Results: It is demonstrated by a comparison of experimental results analysis that 3D-RNT is a suitable candidate for 3D NoC topology. Conclusion: TThe performance of the topologies and routing algorithm for 3D NoC is analysed. 3D-MT is not a suitable candidate for 3D NoC, 3D-ST is a suitable candidate provided interlayer communications are frequent and 3D-RNT is a suitable candidate as interlayer communications are limited.

  6. Novel and anti-inflammatory constituents of Garcinia subelliptica.

    Science.gov (United States)

    Weng, Jing-Ru; Lin, Chun-Nan; Tsao, Lo-Ti; Wang, Jih-Pyang

    2003-05-01

    Four novel phloroglucinol derivatives, garcinielliptones A (1), B (2), C (3), D (4), a novel triterpenoid, garcinielliptone E (5), and three known compounds were isolated from the seeds of Garcinia subelliptica. The structures, including relative configurations, were elucidated by means of spectroscopic data. Known compounds garsubellin A (6) and garcinielliptin oxide (7) showed potent inhibitory effects on the release of beta-glucuronidase, and beta-glucuronidase and histamine, respectively, from peritoneal mast cells stimulated with compound 48/80 in a concentration-dependent manner with IC(50) values of 15.6+/-2.5, and 18.2+/-3.6 and 20.0+/-2.7 microM, respectively. Compound 7 showed potent inhibitory effects on the release of beta-glucuronidase and lysozyme from neutrophils stimulated with formyl-Met-Leu-Phe(fMLP)/cytochalasin B (CB) in a concentration-dependent manner with IC(50) values of 15.7+/-3.0 and 23.9+/-3.2 microM, respectively. Compound 7 also showed potent inhibitory effect on superoxide formation from neutrophils stimulated with fMLP/CB also in a concentration-dependent manner with an IC(50) value of 17.9+/-1.5 microM. PMID:12740842

  7. Investigation of Spectral Band Requirements for Improving Retrievals of Phytoplankton Functional Types

    Directory of Open Access Journals (Sweden)

    Aleksandra Wolanin

    2016-10-01

    Full Text Available Studying phytoplankton functional types (PFTs from space is possible due to recent advances in remote sensing. Though a variety of products are available, the limited number of wavelengths available compared to the number of model parameters needed to be retrieved is still a major problem in using ocean-color data for PFT retrievals. Here, we investigated which band placement could improve retrievals of three particular PFTs (diatoms, coccolithophores and cyanobacteria. In addition to analyzing dominant spectral features in the absorption spectra of the target PFTs, two previously-developed methods using measured spectra were applied to simulated data. Such a synthetic dataset allowed for significantly increasing the number of scenarios and enabled a full control over parameters causing spectral changes. We evaluated the chosen band placement by applying an adapted ocean reflectance inversion, as utilized in the generalized inherent optical properties (GIOP retrieval. Results show that the optimal band settings depend on the method applied to determine the bands placement, as well as on the internal variability of the dataset investigated. Therefore, continuous hyperspectral instruments would be most beneficial for discriminating multiple PFTs, though a small improvement in spectral sampling and resolution does not significantly modify the results. Bands, which could be added to future instruments (e.g., Ocean and Land Colour Instrument (OLCI instrument on the upcoming Sentinel-3B,-3C,-3D, etc., and further satellites in order to enhance PFT retrieval capabilities, were also determined.

  8. Study on The Factors of Effect on Popcorn Coefficient and The Flavor%影响玉米爆花系数及风味的因素研究

    Institute of Scientific and Technical Information of China (English)

    袁旭; 何宁

    2004-01-01

    研究了水分对爆裂玉米爆裂系数的影响,结果表明:籽粒的含水量对爆裂系数和爆花率都有影响,在试验范围内,对爆裂系数贡献最大的是玉米的水分含量,其次是爆花率;黄玉麦的含水量在13.7%时爆裂系数达到46.2,实际生产时控制在13.3%~14.0%为宜.同时选择奶油(A)、食盐(B)、胡椒粉(C)、花椒粉(D)四个因素进行了正交试验,得出最佳风味组合为A3B3C3D4,即奶油11.0%、食盐2.5%、胡椒粉0.5%、花椒粉0.7%.各因素中食盐为主要影响因素,其次为胡椒粉和奶油含量,花椒的含量影响最小.

  9. Electron tunneling through barriers of adjustable width: Role of the image potential and the wetting behavior of Cs by He

    Science.gov (United States)

    Zech, M.; Bromberger, H.; Klier, J.; Leiderer, P.; Wyatt, A. F. G.

    2008-09-01

    Photocurrents from cesium, flowing through gaseous H3e or H4e and also through thin liquid helium films, are investigated as a function of the chemical potential of helium at T=1.33K . At low pressures, the two isotopes behave similarly as the photocurrent is governed by scattering by the gas. At higher pressures, a film of H3e grows on the Cs and forms a tunnel barrier; but for H4e , the film is too thin to form a tunnel barrier below liquid-vapor coexistence. This is because H4e does not wet Cs at this temperature and the finite thickness needed to form a tunnel barrier is larger than the thickness of the thin-film state. H3e enables a continuously variable tunnel barrier thickness to be studied. We show that the image potential is important and confirm that an electron in liquid H3e has a potential energy of 1.0 eV. We find that the thickness d of a helium film is given by ΔC3/d3=-kBTln(p/p0) for films thicker than approximately three monolayers.

  10. Complement and Humoral Adaptive Immunity in the Human Choroid Plexus: Roles for Stromal Concretions, Basement Membranes, and Epithelium.

    Science.gov (United States)

    Moore, G R Wayne; Laule, Cornelia; Leung, Esther; Pavlova, Vladimira; Morgan, B Paul; Esiri, Margaret M

    2016-05-01

    The choroid plexus (CP) provides a barrier to entry of toxic molecules from the blood into the brain and transports vital molecules into the cerebrospinal fluid. While a great deal is known about CP physiology, relatively little is known about its immunology. Here, we show immunohistochemical data that help define the role of the CP in innate and adaptive humoral immunity. The results show that complement, in the form of C1q, C3d, C9, or C9neo, is preferentially deposited in stromal concretions. In contrast, immunoglobulin (Ig) G (IgG) and IgA are more often found in CP epithelial cells, and IgM is found in either locale. C4d, IgD, and IgE are rarely, if ever, seen in the CP. In multiple sclerosis CP, basement membrane C9 or stromal IgA patterns were common but were not specific for the disease. These findings indicate that the CP may orchestrate the clearance of complement, particularly by deposition in its concretions, IgA and IgG preferentially via its epithelium, and IgM by either mechanism.

  11. A CD21 low phenotype, with no evidence of autoantibodies to complement proteins, is consistent with a poor prognosis in CLL.

    Science.gov (United States)

    Nichols, Eva-Maria; Jones, Rachel; Watson, Rachael; Pepper, Chris J; Fegan, Chris; Marchbank, Kevin J

    2015-10-20

    B-cell chronic lymphocytic leukemia (CLL) is characterized by differential BCR signaling and autoimmune complications. Complement modulates B-cell function via C3d and CD21 cross-linked to the B-cell receptor (BCR). We hypothesized that CD21 contributes to BCR signaling and participates in the autoimmunity associated with CLL. We analyzed CD21 expression on 106 CLL patient samples and matched serum from 50 patients for the presence of soluble CD21 and autoantibodies to CR2, CR1, MCP and FH. CD21 expression on CLL B-cells was significantly lower than that expressed on B-cells from age-matched controls (P complement regulator. Low CD21 expression correlated to prognostic subsets of CLL patients, i.e. cases with unmutated IGHV genes (P = 0.0006), high CD38 (P = 0.02) and high ZAP70 expression (P = 0.0017). Low CD21 expression was inversely correlated to the levels of phosphotyrosine induced in CLL cells following BCR ligation with αIgM (r2 = -0.21). Importantly, lower CD21 expression was also predictive for reduced overall survival (P = 0.005; HR = 2.7). In conclusion, we showed that reduced expression of CD21 on CLL B-cells appears functionally relevant and was associated with poor clinical outcomes.

  12. Calcium-dependent and calcium-independent signals in the conglutinin-binding assay (KgBa) for immune complexes. Influence of anti-collagen-antibodies

    DEFF Research Database (Denmark)

    Holmskov, U; Haas, Henning de; Teisner, B;

    1992-01-01

    A solid phase ELISA conglutinin-binding assay (KgBa) was evaluated for the detection of circulating immune complexes. ELISA wells were coated with purified bovine conglutinin and incubated with test sera. Bound IgG was detected with enzyme labelled anti-immunoglobulin. Heat aggregated IgG which had...... been "solubilized" (i.e., complement treated by incubation with serum) was employed as a reference. The binding of the complement-reacted IgG to solid phase conglutinin was found to be calcium-dependent and inhibitable with N-acetyl-D-glucosamine (GlcNAc). Prolonged incubation (4 days) of aggregated Ig......G with serum at 37 degrees C abolished the binding to conglutinin, a finding consistent with the complete degradation of deposited C3b to C3c and C3d. The solubilized IgG that bound to solid phase conglutinin was found by gel chromatography to be of high molecular weight (greater than 600 kDa). Binding of Ig...

  13. Structural optimization and evaluation of butenolides as potent antifouling agents: modification of the side chain affects the biological activities of compounds

    KAUST Repository

    Li, Yongxin

    2012-09-01

    A recent global ban on the use of organotin compounds as antifouling agents has increased the need for safe and effective antifouling compounds. In this study, a series of new butenolide derivatives with various amine side chains was synthesized and evaluated for their anti-larval settlement activities in the barnacle, Balanus amphitrite. Side chain modification of butenolide resulted in butenolides 3c-3d, which possessed desirable physico-chemical properties and demonstrated highly effective non-toxic anti-larval settlement efficacy. A structure-activity relationship analysis revealed that varying the alkyl side chain had a notable effect on anti-larval settlement activity and that seven to eight carbon alkyl side chains with a tert-butyloxycarbonyl (Boc) substituent on an amine terminal were optimal in terms of bioactivity. Analysis of the physico-chemical profile of butenolide analogues indicated that lipophilicity is a very important physico-chemical parameter contributing to bioactivity. © 2012 Copyright Taylor and Francis Group, LLC.

  14. Identification and Characterization of Porcine Kobuvirus Variant Isolated from Suckling Piglet in Gansu Province, China

    Directory of Open Access Journals (Sweden)

    Xianzhu Xia

    2013-10-01

    Full Text Available Kobuviruses comprise three species, the Aichivirus A, Aichivirus B, and Aichivirus C (porcine kobuvirus. Porcine kobuvirus is endemic to pig farms and is not restricted geographically but, rather, is distributed worldwide. The complete genomic sequences of four porcine kobuvirus strains isolated during a diarrhea outbreak in piglets in the Gansu province of China were determined. Two of these strains exhibited variations relative to the traditional strains. The potential 3C/3D cleavage sites of the variant strains were Q/C, which differed from the Q/S in the traditional porcine kobuvirus genome. A 90-nucleotide deletion in the 2B protein and a single nucleotide insertion in the 3′UTR were found in the variant strains. The VP1 regions of all four porcine kobuviruses in our study were highly variable (81%–86%. Ten common amino acid mutations were found specifically at certain positions within the VP1 region. Significant recombination sites were identified using SimPlot scans of whole genome sequences. Porcine kobuviruses were also detected in pig serum, indicating that the virus can escape the gastrointestinal tract and travel to the circulatory system. These findings suggest that mutations and recombination events may have contributed to the high level of genetic diversity of porcine kobuviruses and serve as a driving force in its evolution.

  15. Identification and characterization of porcine kobuvirus variant isolated from suckling piglet in Gansu province, China.

    Science.gov (United States)

    Fan, Shengtao; Sun, Heting; Ying, Ying; Gao, Xiaolong; Wang, Zheng; Yu, Yicong; Li, Yuanguo; Wang, Tiecheng; Yu, Zhijun; Yang, Songtao; Zhao, Yongkun; Qin, Chuan; Gao, Yuwei; Xia, Xianzhu

    2013-10-01

    Kobuviruses comprise three species, the Aichivirus A, Aichivirus B, and Aichivirus C (porcine kobuvirus). Porcine kobuvirus is endemic to pig farms and is not restricted geographically but, rather, is distributed worldwide. The complete genomic sequences of four porcine kobuvirus strains isolated during a diarrhea outbreak in piglets in the Gansu province of China were determined. Two of these strains exhibited variations relative to the traditional strains. The potential 3C/3D cleavage sites of the variant strains were Q/C, which differed from the Q/S in the traditional porcine kobuvirus genome. A 90-nucleotide deletion in the 2B protein and a single nucleotide insertion in the 3'UTR were found in the variant strains. The VP1 regions of all four porcine kobuviruses in our study were highly variable (81%-86%). Ten common amino acid mutations were found specifically at certain positions within the VP1 region. Significant recombination sites were identified using SimPlot scans of whole genome sequences. Porcine kobuviruses were also detected in pig serum, indicating that the virus can escape the gastrointestinal tract and travel to the circulatory system. These findings suggest that mutations and recombination events may have contributed to the high level of genetic diversity of porcine kobuviruses and serve as a driving force in its evolution. PMID:24145960

  16. The mode of action of immunological adjuvants.

    Science.gov (United States)

    Allison, A C

    1998-01-01

    Adjuvants augment immune responses to antigens and influence the balance between cell-mediated and humoral responses, as well as the isotypes of antibodies formed. New adjuvant formulations include antigen-carrying vehicles and small molecules with immunomodulating activity. Widely used two-phase vehicles comprise liposomes and microfluidized squalene or squalane emulsions. These are believed to target antigens to antigen-presenting cells, including dendritic cells (DC), follicular dendritic cells (FDC) and B-lymphocytes. Activation of complement generates C3d, which binds CR2 (CD21) on FDC and B-lymphocytes, thereby stimulating the proliferation of the latter and the generation of B-memory. Targeting of antigens to DC may favour cell-mediated immunity. Immunomodulating agents induce the production of cytokine cascades. In a primary cascade at injection sites TNF-alpha, GM-CSF and IL-1 are produced. TNF-alpha promotes migration of DC to lymphoid tissues, while GM-CSF and IL-1 accelerate the maturation of DC into efficient antigen-presenting cells for T-lymphocytes. In a secondary cytokine cascade in draining lymph nodes, DC produce IL-12, which induces Th1 responses with the production of IFN-gamma. The cytokines elicit cell-mediated immune responses and the formation of antibodies of protective isotypes, such as IgG2a in the mouse and IgG1 in humans. Antibodies of these isotypes activate complement and collaborate with antibody-dependent effector cells in protective immune responses.

  17. Power Spectrum of Cerenkov Radiation from Laser Wakefield in Magnetized Plasma

    Science.gov (United States)

    Gao, Hong; Higashiguchi, Takeshi; Yugami, Noboru; Ito, Hiroaki; Nishida, Yasushi

    2000-10-01

    An angle and radiation frequecy distribution of the output power of the electromagnetic wave radiation from the laser wakefield in a magnetized plasma (Cerenkov wakes radiaiton) have been calculated. The magnetic field here is applied for the far field electromagnetic wave radiation = requirement. The radiation frequency is confined from ωp to = ω_h. The electromagnetic wave generation originates from the coupling between the DC perpendicular magnetic field and the plasma electron longitudinal = disturbance caused by the laser ponderomotive force. Under Coulomb gauge condition, the wave equation can be completely partitioned for the scale potential = and the vector field, so it can be easily obtained from the near zone static = field and far zone radiation field. The former has well been studied as the = static wakefield acceleration. Here we wish to present the detailed study on = the feature of the radiated electromagnetic field for the later case. The radiation = power spectrum which depends on the magnetic field, the laser pulse length, = the radiation frequency and the corresponding refraction index have been = given. The analysis shows that at the direction of \\cos θ= c=3D1/β n, where n is the refraction index of the magnetized plasma, the output = power has the maximum which satisfies the Cerenkov radiation angle condition, = so that the output power for the radiation frequency of ωp = is mainly located at the forward direction.

  18. Prelimary Study on Using Compound Biological Insecticides to Control Dendrolimus kikuchii%复合生物杀虫剂防治思茅松毛虫的初步研究

    Institute of Scientific and Technical Information of China (English)

    邓秀明

    2002-01-01

    应用白僵菌、苏云金杆菌、马尾松毛虫质型多角体病毒(DCPV)和15%保丰等4种杀虫剂对2~3龄思茅松毛虫幼虫进行了毒力测定.并通过林间正交试验设计筛选出了复合生物杀虫剂最佳组合A3B1C3D1,即白僵菌1.4×106孢子*ml-1+苏云金杆菌1.6×108孢子*ml-1+DCPV 5×106PIB*ml-1+15%保丰4000倍液.研究表明在复合杀虫剂中保丰、苏云金杆菌对防治效果有显著影响.林间大面积防治试验表明,复合杀虫剂的防治效果优于单一生物杀虫剂.

  19. Effect of Wire-EDM cutting parameters on material removal rate of titanium alloy (Ti6Al4V)

    Science.gov (United States)

    Azam, N.; Afendi, M.

    2016-07-01

    In this study, titanium alloy (Ti6Al4V) which is also known as difficult to cut material is used as workpiece. Seven main parameters namely pulse duration (A), pulse interval (B), servo voltage (C), ignition pulse current (D), wire tension (E), wire speed (F) and dielectric pressure (G) have been experimentally studied by using Taguchi method as well as the determination of optimum parameters for material removal rate (MRR). Analysis of variance (ANOVA) has been used for recognizing the level of significant of WEDM cutting parameter for optimizing MRR and the result found that pulse duration and servo voltage give significant effect on MRR. While according to Signal to Noise (S/N) ratio response table for MRR, the parameters combination of A3B3C3D3E1F3G3 give the optimum value for MRR. It is also observed that the predicted results agree with the experimental values within an error of 4.6 %.

  20. Rare Occurrence of 3 "H": Hypercalcemia, Hemolytic Anemia and Hodgkin's Lymphoma.

    Science.gov (United States)

    Jain, Ankur; Malhotra, Pankaj; Prakash, Gaurav; Varma, Subhash; Kumar, Narender; Das, Asim

    2016-06-01

    Clinicians in hematology practice commonly encounter anemia, hypercalcemia and renal failure, which when present in combination evoke a diagnostic workup for multiple myeloma. We report a 71-years old lady who presented to our hematology clinic with fever and easy fatiguability of 3 months duration and on investigations was found to have anemia and hypercalcemia. Direct Coomb's test characterized the anemia as complement mediated (anti-C3d) hemolysis. Biochemical investigations revealed normal 25(OH) Vitamin D3 and suppressed Parathormone levels and a negative workup for plasma cell dyscrasias, sarcoidosis and autoimmune disorders. CT scan revealed a paravertebral mass with cervical, supraclavicular and abdominal lymphadenopathy along with splenomegaly and left pleural effusion. Biopsy from the paravertebral mass confirmed the diagnosis of Hodgkin's disease (nodular sclerosis) using immunohistochemistry. Bone marrow examination suggested infiltration by lymphoma. Hypercalcemia was managed with saline and zoledronic acid. Administration of prednisolone (1 mg/kg/day) along with chemotherapy (ABVD regimen) led to normalization of calcium and hemoglobin levels. However, hemolysis recurred 2 weeks later and hence, Rituximab (375 mg/m(2)) was administered on a weekly schedule for 4 doses and ABVD (2 weekly) was continued, which brought hemolysis under control. Co-occurrence of two paraneoplastic manifestations (complement mediated hemolytic anemia and hypercalcemia) in Hodgkin's lymphoma is very unusual. Present report aims not only to highlight a rare presentation of Hodgkin's lymphoma but also focus on the role of Rituximab in controlling hemolysis associated with this disease. PMID:27408382

  1. Isolation of a sp. nov. Ljungan virus from wild birds in Japan.

    Science.gov (United States)

    Mitake, Hiromichi; Fujii, Yuji; Nagai, Makoto; Ito, Naoto; Okadera, Kota; Okada, Kazuma; Nakagawa, Kento; Kishimoto, Mai; Mizutani, Tetsuya; Okazaki, Katsunori; Sakoda, Yoshihiro; Takada, Ayato; Sugiyama, Makoto

    2016-08-01

    Ljungan virus (LV) has been isolated/detected from rodents in a limited area including European countries and the USA. In this study, we isolated an LV strain from faecal samples of wild birds that had been collected in Japan, and determined the nearly complete sequence of the genome. Sequence analyses showed that the isolate possesses an LV-like genomic organization: 5UTR-VP0-VP3-VP1-2A1-2A2-2B-2C-3A-3B-3C-3D-3UTR. Phylogenetic and similarity analyses based on the VP1 region indicated that the strain constitutes a novel genotype within LV. In addition, we identified species origin of the faeces as gull species by using the DNA barcoding technique. These data suggested that the novel LV strain infected a gull species, in which the virus had not been identified. Taken together, this study has provided the first evidence of the presence of a novel LV in Japan, highlighting the possibility of LV infection in birds. PMID:27207304

  2. Fluctuations in the Microwave Conductivity of YBCO Single Crystals in Zero DC Magnetic Field

    Science.gov (United States)

    Anlage, Steven; Mao, Jian; Booth, James; Wu, Dong-Ho; Peng, J. L.

    1996-03-01

    We present a quantitative analysis of finite frequency fluctuation conductivity above and below Tc in cuprate superconductors in zero dc magnetic field.(S. M. Anlage, J. Mao, J. C. Booth, D. H. Wu, and J. L. Peng, Phys. Rev. B 53), Feb. 1, 1996. In a YBa_2Cu_3O_7-δ crystal showing a linear in temperature increase of the magnetic penetration depth at low temperatures, we find that two-dimensional finite-frequency Gaussian conductivity fluctuations above Tc cross over into a slower divergence of the conductivity as Tc is approached from above. We find that the critical regime above Tc is less than about 0.6 K wide, although inhomogeneities in the crystal may also dominate the conductivity in this temperature range. At and below T_c, 3D fluctuations dominate the conductivity, with evidence of 3D XY critical scaling of the imaginary part of the conductivity down to 5 K below T_c. Supported by the NSF NYI program (DMR-9258183), and NSF grant DMR-9123198.

  3. Shock tube measurements of the branching ratios of propene + OH -> products

    KAUST Repository

    Khaled, Fathi

    2014-07-25

    Absolute rate coefficients for the reaction of OH radical with propene (C3H6) and five deutrated isotopes, propene-1-d1 (CDHCHCH3), propene-1,1-d2 (CD2CHCH3), propene-2-d1 (CH2CDCH3), propene-3,3,3-d3 (CH2CHCD3), and propene-d6 (C3D6), were measured in a shock tube behind reflected shock conditions over the temperature range of 812 K – 1460 K and pressures near 1 atm. The reaction progress was followed by monitoring OH radical near 306.7 nm using UV laser absorption. The first experimental measurements for the branching ratio of the title reaction are reported and compared with theoretical calculations. The allylic H atom abstraction of propene by OH radicals was found to be the most dominant reaction pathway followed by propen-1-yl and propen-2-yl channels over the entire temperature range of this study which is in line with theoretical predictions. Arrhenius parameters for various site-specific rate coefficients are provided for kinetic modeling.

  4. Dosimetry of cone beam computed tomography scanning for diagnosis and planning in implant dentistry

    International Nuclear Information System (INIS)

    Full text: The radiation dose and estimate the radiation induced risk of cancer and morpho functional alterations according to BEIR VII (2006) and recommendations of the ICRP 103 (2007) were measured in cone beam computed tomography (CBCT) scanning (Tc Kodak 9000C 3D) in different oral and maxillofacial regions for diagnosis and planning in implant dentistry for each examination protocol: jaw full, maxilla full and jaw and maxilla full associated. Thermoluminescent dosimeters (TLD- 100 H) were placed in an Alderson-Rando in regions corresponding to the crystalline, parotid, submandibular and thyroid glands and ovaries. The highest values for entrance skin dose were observed in the region of the parotid and submandibular glands, 9.612 mGy to 7.912 mGy and 8.818 mGy to 0.483 mGy, respectively. All examination protocols presented on the right and left sides in the region of the submandibular gland the highest values for absorbed dose (D). In the jaw full exam the thyroid glands on both sides presented highest dose values than maxilla full exam. This study allowed measuring the entrance skin dose and the absorbed dose (D) highlighting a dosimetric preponderance to the salivary glands. With danger of to radiation that induces cancer risk was observed that the age group most likely to have to risk of cancer was 20 years, compared to 30, 40, 50, 60,70 and 80 years. (Author)

  5. Hydrothermal synthesis and characterization of the first mixed alkali borate-nitrate K3Na[B6O9(OH)3]NO3

    International Nuclear Information System (INIS)

    The first mixed alkali borate-nitrate K3Na[B6O9(OH)3]NO3 was synthesized under hydrothermal conditions from Na2B4O7·10H2O and K2B4O7·4H2O using KNO3 as a nitrate source. The compound crystallizes in the space group Pnnm (no. 58) with the lattice parameters a=1320.8(3), b=910.7(2), and c=1232.5(3) pm (Z=4). Isolated Sechserrings formed by BO4 and BO3 groups are linked through hydrogen bridges to form a three-dimensional network. - Graphical abstract: The first mixed alkali borate-nitrate K3Na[B6O9(OH)3]NO3 was synthesized under hydrothermal conditions from Na2B4O7·10H2O and K2B4O7·4H2O using KNO3 as a nitrate source. - Highlights: • The first mixed alkali borate-nitrate K3Na[B6O9(OH)3]NO3 is reported. • Hydrothermal conditions (240 °C, 3d) were used for the synthesis of K3Na[B6O9(OH)3]NO3. • Borate Sechserrings are interconnected through hydrogen-bonding

  6. Calculation of the reactivity worth for TRIGA core fuel elements by means of the two-dimensional, two-group perturbation theory

    International Nuclear Information System (INIS)

    A two-dimensional, two-group perturbation theory calculation method has been proposed for the rapid and accurate calculation of the reactivity worth for TRIGA core fuel elements. The method requires shorter computation times and provides almost the same level of accuracy as a conventional direct eigenvalue calculation method using the CITATION code. Values for changes in macroscopic cross-sections and diffusion coefficients are obtained from cell calculation. The reactivity worth for each individual fuel element is calculated on the basis of the above-mentioned changes, by means of the two-group, first order perturbation method using normal and adjoint neutron fluxes calculated beforehand for a normal core. The method was applied to a 250 kW TRIGA Mark-II reactor. The results of the calculations are in agreement with the experimental values for fuel elements in the locations C3, D8, E7 and F4. The reactivity worth for the TRIGA core fuel element placed in location B2 calculated by means of this method is approximately 5% greater than that calculated by means of the CITATION code which is based on a conventional direct eigenvalue calculation method. (orig.)

  7. A Simple and Novel Strategy for the Production of a Pan-specific Antiserum against Elapid Snakes of Asia.

    Science.gov (United States)

    Ratanabanangkoon, Kavi; Tan, Kae Yi; Eursakun, Sukanya; Tan, Choo Hock; Simsiriwong, Pavinee; Pamornsakda, Teeraporn; Wiriyarat, Witthawat; Klinpayom, Chaiya; Tan, Nget Hong

    2016-04-01

    Snakebite envenomation is a serious medical problem in many tropical developing countries and was considered by WHO as a neglected tropical disease. Antivenom (AV), the rational and most effective treatment modality, is either unaffordable and/or unavailable in many affected countries. Moreover, each AV is specific to only one (monospecific) or a few (polyspecific) snake venoms. This demands that each country to prepare AV against its local snake venoms, which is often not feasible. Preparation of a 'pan-specific' AV against many snakes over a wide geographical area in some countries/regions has not been possible. If a 'pan-specific' AV effective against a variety of snakes from many countries could be prepared, it could be produced economically in large volume for use in many countries and save many lives. The aim of this study was to produce a pan-specific antiserum effective against major medically important elapids in Asia. The strategy was to use toxin fractions (TFs) of the venoms in place of crude venoms in order to reduce the number of antigens the horses were exposed to. This enabled inclusion of a greater variety of elapid venoms in the immunogen mix, thus exposing the horse immune system to a diverse repertoire of toxin epitopes, and gave rise to antiserum with wide paraspecificity against elapid venoms. Twelve venom samples from six medically important elapid snakes (4 Naja spp. and 2 Bungarus spp.) were collected from 12 regions/countries in Asia. Nine of these 12 venoms were ultra-filtered to remove high molecular weight, non-toxic and highly immunogenic proteins. The remaining 3 venoms were not ultra-filtered due to limited amounts available. The 9 toxin fractions (TFs) together with the 3 crude venoms were emulsified in complete Freund's adjuvant and used to immunize 3 horses using a low dose, low volume, multisite immunization protocol. The horse antisera were assayed by ELISA and by in vivo lethality neutralization in mice. The findings were: a

  8. A Simple and Novel Strategy for the Production of a Pan-specific Antiserum against Elapid Snakes of Asia.

    Science.gov (United States)

    Ratanabanangkoon, Kavi; Tan, Kae Yi; Eursakun, Sukanya; Tan, Choo Hock; Simsiriwong, Pavinee; Pamornsakda, Teeraporn; Wiriyarat, Witthawat; Klinpayom, Chaiya; Tan, Nget Hong

    2016-04-01

    Snakebite envenomation is a serious medical problem in many tropical developing countries and was considered by WHO as a neglected tropical disease. Antivenom (AV), the rational and most effective treatment modality, is either unaffordable and/or unavailable in many affected countries. Moreover, each AV is specific to only one (monospecific) or a few (polyspecific) snake venoms. This demands that each country to prepare AV against its local snake venoms, which is often not feasible. Preparation of a 'pan-specific' AV against many snakes over a wide geographical area in some countries/regions has not been possible. If a 'pan-specific' AV effective against a variety of snakes from many countries could be prepared, it could be produced economically in large volume for use in many countries and save many lives. The aim of this study was to produce a pan-specific antiserum effective against major medically important elapids in Asia. The strategy was to use toxin fractions (TFs) of the venoms in place of crude venoms in order to reduce the number of antigens the horses were exposed to. This enabled inclusion of a greater variety of elapid venoms in the immunogen mix, thus exposing the horse immune system to a diverse repertoire of toxin epitopes, and gave rise to antiserum with wide paraspecificity against elapid venoms. Twelve venom samples from six medically important elapid snakes (4 Naja spp. and 2 Bungarus spp.) were collected from 12 regions/countries in Asia. Nine of these 12 venoms were ultra-filtered to remove high molecular weight, non-toxic and highly immunogenic proteins. The remaining 3 venoms were not ultra-filtered due to limited amounts available. The 9 toxin fractions (TFs) together with the 3 crude venoms were emulsified in complete Freund's adjuvant and used to immunize 3 horses using a low dose, low volume, multisite immunization protocol. The horse antisera were assayed by ELISA and by in vivo lethality neutralization in mice. The findings were: a

  9. A Simple and Novel Strategy for the Production of a Pan-specific Antiserum against Elapid Snakes of Asia.

    Directory of Open Access Journals (Sweden)

    Kavi Ratanabanangkoon

    2016-04-01

    Full Text Available Snakebite envenomation is a serious medical problem in many tropical developing countries and was considered by WHO as a neglected tropical disease. Antivenom (AV, the rational and most effective treatment modality, is either unaffordable and/or unavailable in many affected countries. Moreover, each AV is specific to only one (monospecific or a few (polyspecific snake venoms. This demands that each country to prepare AV against its local snake venoms, which is often not feasible. Preparation of a 'pan-specific' AV against many snakes over a wide geographical area in some countries/regions has not been possible. If a 'pan-specific' AV effective against a variety of snakes from many countries could be prepared, it could be produced economically in large volume for use in many countries and save many lives. The aim of this study was to produce a pan-specific antiserum effective against major medically important elapids in Asia. The strategy was to use toxin fractions (TFs of the venoms in place of crude venoms in order to reduce the number of antigens the horses were exposed to. This enabled inclusion of a greater variety of elapid venoms in the immunogen mix, thus exposing the horse immune system to a diverse repertoire of toxin epitopes, and gave rise to antiserum with wide paraspecificity against elapid venoms. Twelve venom samples from six medically important elapid snakes (4 Naja spp. and 2 Bungarus spp. were collected from 12 regions/countries in Asia. Nine of these 12 venoms were ultra-filtered to remove high molecular weight, non-toxic and highly immunogenic proteins. The remaining 3 venoms were not ultra-filtered due to limited amounts available. The 9 toxin fractions (TFs together with the 3 crude venoms were emulsified in complete Freund's adjuvant and used to immunize 3 horses using a low dose, low volume, multisite immunization protocol. The horse antisera were assayed by ELISA and by in vivo lethality neutralization in mice. The

  10. A Simple and Novel Strategy for the Production of a Pan-specific Antiserum against Elapid Snakes of Asia

    Science.gov (United States)

    Ratanabanangkoon, Kavi; Tan, Kae Yi; Eursakun, Sukanya; Tan, Choo Hock; Simsiriwong, Pavinee; Pamornsakda, Teeraporn; Wiriyarat, Witthawat; Klinpayom, Chaiya; Tan, Nget Hong

    2016-01-01

    Snakebite envenomation is a serious medical problem in many tropical developing countries and was considered by WHO as a neglected tropical disease. Antivenom (AV), the rational and most effective treatment modality, is either unaffordable and/or unavailable in many affected countries. Moreover, each AV is specific to only one (monospecific) or a few (polyspecific) snake venoms. This demands that each country to prepare AV against its local snake venoms, which is often not feasible. Preparation of a ‘pan-specific’ AV against many snakes over a wide geographical area in some countries/regions has not been possible. If a ‘pan-specific’ AV effective against a variety of snakes from many countries could be prepared, it could be produced economically in large volume for use in many countries and save many lives. The aim of this study was to produce a pan-specific antiserum effective against major medically important elapids in Asia. The strategy was to use toxin fractions (TFs) of the venoms in place of crude venoms in order to reduce the number of antigens the horses were exposed to. This enabled inclusion of a greater variety of elapid venoms in the immunogen mix, thus exposing the horse immune system to a diverse repertoire of toxin epitopes, and gave rise to antiserum with wide paraspecificity against elapid venoms. Twelve venom samples from six medically important elapid snakes (4 Naja spp. and 2 Bungarus spp.) were collected from 12 regions/countries in Asia. Nine of these 12 venoms were ultra-filtered to remove high molecular weight, non-toxic and highly immunogenic proteins. The remaining 3 venoms were not ultra-filtered due to limited amounts available. The 9 toxin fractions (TFs) together with the 3 crude venoms were emulsified in complete Freund’s adjuvant and used to immunize 3 horses using a low dose, low volume, multisite immunization protocol. The horse antisera were assayed by ELISA and by in vivo lethality neutralization in mice. The findings

  11. Survey on Topologies of Three-Dimensional Network on Chip%三维片上网络拓扑结构研究综述

    Institute of Scientific and Technical Information of China (English)

    张大坤; 宋国治; 王莲莲; 黄翠

    2015-01-01

    Three-dimensional network on chip (3D NoC) is developed based on three-dimensional integrated circuit (3D IC), system on chip (SoC) and two-dimensional network on chip (2D NoC). 3D NoC is mainly used to solve the problems such as communication bottleneck of highly integrated chips. It has attracted great attention from both aca-demia and industry at home and abroad. 3D NoC topology structure reflects the layout and connectivity of communi-cations node in the chip, which is crucial for the performance of 3D chip. This paper introduces 2D NoC, the evolu-tion from 2D NoC to 3D NoC, the advantages and problems of adopting 3D NoC and the key technical issues which can be solved by 3D NoC, and analyzes the overall development of 3D NoC. 3D topology is one of the key prob-lems in the design of 3D NoC. This paper mainly studies the different classification methods for 3D NoC topology and divides 3D NoC topologies into 9 categories in terms of communication, then gives a thorough study of 3D NoC topology structures with comparison and analysis of the characteristics for each topology structure. Finally, this paper indicates the possible future research development of 3D NoC topology.%三维片上网络(three-dimensional network on chip ,3D NoC)是在三维集成电路(three-dimensional integrated circuit,3D IC)、片上系统(system on chip,SoC)和二维片上网络(two-dimensional network on chip,2D NoC)的基础上发展起来的,主要解决高集成度芯片通信瓶颈等问题,已引起国内外学术界和产业界的高度重视。3D NoC拓扑结构体现了通信节点在芯片中的布局与连接,对三维芯片性能起决定性作用。简介了2D NoC、2D NoC到3D NoC的演变、3D NoC的优点与存在的问题以及3D NoC解决的关键技术问题,分析了3D NoC总体发展状况。三维拓扑结构是3D NoC设计中的关键问题之一,重点研究了3D NoC拓扑结构的分类方法,从通信角度将3D No

  12. Analysis of Serum Proteom after Intravenous Injection of cultivated wild ginseng pharmacopuncture

    Directory of Open Access Journals (Sweden)

    Dong-Hee,Lee

    2006-06-01

    Full Text Available Objectives : To observe the changes in the serum proteins after intravenous injection of cultivated wild ginseng pharmacopuncture. Methods : Blood was collected before and after the administration of cultivated wild ginseng pharmacopuncture and only the serum was taken. Then differences in the spots on the scanned image after carrying out 2-Dimensional electrophoresis were located and conducted mass analysis and protein identification. Results : Following results were obtained from the comparative analysis of serum proteins before and after the administration of cultivated wild ginseng pharmacopuncture. 1. 28 spots were identified before and after the administration. 2. In confirming manifestation degree, spots with more than two-times increase were 204, 1302, 2205, 3105, 7104, 8006, spots with more than one-time increase were 1101, 1505, 2013, 2403, 3009, 3010, 4002, 4009, 6704, 8101, and spots with decrease were 205, 801, 803, 3205, 5202, 6105, 6106, 7103, 9001, 9003. 3. After conducting protein identification, proteins 205, 804, 1302, 4009, 6105, 6106 are unidentified yet, and 1l01 is unnamed protein. Protein 204 is identified as complement receptor CR2-C3d, 801 as YAPl protein, 803 as antitrypsin polymer, 1505 as PRO0684, 2013 and 3010 as proapolipoprotein, 2205 as USP48, 2403 as vitamin D binding protein, 3009 as complement component 4A preprotein, 3105 as immunoglobulin lambda chain, 3205 as transthyretin, 4002 as Ras-related protein Ral-A, 4204 as beta actin, 5202 and 7104 as apolipoprotein Ll, 6704 as alpha 2 macroglobulin precursor, 7103 as complement component 3 precursor, 8006 as testis-specific protein Y, 8101 as transferrin, 9001 as (Alpha-Oxy, Beta-(Cl12gdeoxy T-State Human Hemoglobin, and 9003 as human hemoglobin. 4. Immune protein CR2-C3d(204, which acts against microbes and pathogenic organisms, was increased by more than two-times after the administration of pharmacopuncture. 5. Antitrypsin(803, which is secreted with

  13. A novel optical method for estimating the near-wall volume fraction in granular flows

    Science.gov (United States)

    Sarno, Luca; Nicolina Papa, Maria; Carleo, Luigi; Tai, Yih-Chin

    2016-04-01

    Geophysical phenomena, such as debris flows, pyroclastic flows and rock avalanches, involve the rapid flow of granular mixtures. Today the dynamics of these flows is far from being deeply understood, due to their huge complexity compared to clear water or monophasic fluids. To this regard, physical models at laboratory scale represent important tools for understanding the still unclear properties of granular flows and their constitutive laws, under simplified experimental conditions. Beside the velocity and the shear rate, the volume fraction is also strongly interlinked with the rheology of granular materials. Yet, a reliable estimation of this quantity is not easy through non-invasive techniques. In this work a novel cost-effective optical method for estimating the near-wall volume fraction is presented and, then, applied to a laboratory study on steady-state granular flows. A preliminary numerical investigation, through Monte-Carlo generations of grain distributions under controlled illumination conditions, allowed to find the stochastic relationship between the near-wall volume fraction, c3D, and a measurable quantity (the two-dimensional volume fraction), c2D, obtainable through an appropriate binarization of gray-scale images captured by a camera placed in front of the transparent boundary. Such a relation can be well described by c3D = aexp(bc2D), with parameters only depending on the angle of incidence of light, ζ. An experimental validation of the proposed approach is carried out on dispersions of white plastic grains, immersed in various ambient fluids. The mixture, confined in a box with a transparent window, is illuminated by a flickering-free LED lamp, placed so as to form a given ζ with the measuring surface, and is photographed by a camera, placed in front of the same window. The predicted exponential law is found to be in sound agreement with experiments for a wide range of ζ (10° flows. A 2m-long laboratory flume, with an upper reservoir

  14. THE METHOD OF NUMERICAL MODELING FOR EXISTING RC COMPONENTS BASED ON MATERIAL DEGRATION%基于材料劣化的既有混凝土构件数值建模方法研究

    Institute of Scientific and Technical Information of China (English)

    郑山锁; 杨威; 秦卿; 田微

    2015-01-01

    基于ABAQUS,以多龄期混凝土构件为研究对象,在数值建模方面,采用三维实体线性减缩单元C3 D8 R和两结点三维单元T3 D2模拟混凝土材料、内嵌钢筋的力学行为,将指数衰减摩擦模型用于锈蚀钢筋与混凝土间接触问题上,并将Hsich-Ting-Chen四参数强度准则作为混凝土材料的破坏准则;在材料性能退化方面,基于修正斜压场理论,以锈蚀箍筋、纵筋、受压区锈胀开裂混凝土及核心区约束混凝土为对象,综合各既有材料退化模型,预测了材料退化后的力学性能,得到了开裂混凝土、锈蚀钢筋、混凝土及其之间黏结滑移的本构模型。进而,采用多龄期混凝土构件抗震性能试验研究结果,对提出的基于ABAQUS软件平台的锈蚀混凝土构件数值建模理论进行了可靠性验证,结果表明:所建立的数值建模理论可以有效地模拟锈蚀混凝土构件的抗震性能退化规律,为既有混凝土结构的数值建模理论提供了一种有效的研究方法。%Based on finite element program ABAQUS , regarding RC multi-age components as research object , the unit C3D8R and unit T3D2 were used to simulate the mechanical behavior of concrete and reinforcement , and the superiority of exponential damping friction model for handling with the problem of contact between corrosion reinforcement and concrete was obviously exhibited , then the Hsich-Ting-Chen strength criterion was taken as concrete failure criterion .The loss of the cross sectional area of reinforcement bars , reduction of the cover and core concrete strength were modified by the single-factor time-dependent corrosion rate .Considering the cracking and spalling in the compressed concrete of compression zone caused by reinforcement corrosion , the modified compression-field ( MCF) was used to predict the time-dependent compressed concrete strength .Finally the modified material constitutive models of

  15. Thickness distribution of adolescent palatal bone studied by CBCT%青少年腭部骨质厚度的 CBCT 研究

    Institute of Scientific and Technical Information of China (English)

    陈建明; 苏小元

    2014-01-01

    目的:研究青少年腭部骨质厚度分布,为腭部植入微种植体提供参考。方法:用 NNT Viewer 软件将20例青少年正畸患者的头颅锥形束 CT 扫描数据的腭部情况进行分析,以切牙孔为原点,间隔2 mm,矢状方向分为1~10共10个点,横向分为 A ~F 共6个点,测量统计60个点位的骨厚度,并行统计学分析。结果:B2、B3、C2、C3、D3、E3、E4、F4、F5各点间差异无统计学意义(P >0.05);而 F3点与 B2、B3、C2、C3、D3、E3、E4、F4、F5各点间的差异具有统计学意义(P <0.05);D3与 D4间差异具有统计学意义(P <0.05)。结论:适于微种植体植入的部位在腭中缝左右2~4 mm、离切牙孔4~6 mm 区域,而距腭中缝8~10 mm、离切牙孔6~8 mm 区域较为安全,同时可获得厚度为6 mm 左右的骨组织支持。%Objective:To study the thickness distribution palatal bone in adolescents and provide a clinical reference for implanting mini-screws.Methods:Cone-beam CT head scan data of palate of 20 adolescent orthodontic patients were measured with NNT Viewer software.60 points of the palate bone on one side were designed as 1 -10 in sagittal direction and as A -F in transvers direction with incisive foramen as the point of A and 0,the distance between each 2 adjacent points was 2 mm.The bone thickness of the 60 points were measured and statistically analyzed.Results:There were no significant differences among B2,B3,C2,C3,D3,E3,E4,F4 and F5(P >0.05).Statistically significant difference was found between F3 and B2 or B3,C2,C3,D3,E3,E4,F4 and F5(P <0.05).There was significant difference between D3 and D4(P <0.05).Conclusion:The appropriate areas for implanting mini-screws in palate may be about 2 -4 mm near the palatal suture and 4 -6 mm behind incisor canal,and 8 -10 mm near the palatal su-ture,6 -8 mm behind incisor canal.Those regions are safe for implanting mini-screws and can provide about 6 mm bone

  16. Analysis of Serum proteom before and after Intravenous Injection of wild ginseng herbal acupuncture

    Directory of Open Access Journals (Sweden)

    Tae-Sik Kang

    2004-12-01

    Full Text Available Objectives : To observe changes in the serum proteins before and after intravenous injection of wild ginseng herbal acupuncture. Methods : Blood was collected before and after the administration of wild ginseng herbal acupuncture and only the serum was centrifuged. Then differences in the spots on the scanned image after running 2-Dimensional electrophoresis were located and conducted mass analysis and protein identification. Results : Following results were obtained from the comparative analysis of serum proteins before and after the administration of wild ginseng herbal acupuncture. 1. 28 spots were identified before and after the administration. 2. In confirming manifestation degree, spots with more than two-times increase were 204, 803, 1505, 2205, 3105, 7104, 9001 spots, with more than one-time increase were 1101, 1302, 2013, 3009, 3010, 4002, 4009, 6706, 7103, 8006, 8101, and spots with decrease were 205, 801, 3205, 5202, 6105. 3. After conducting protein identification, proteins 205, 804, 1302, 4009, 6105, 6106 are unidentified yet, and 1101 is unnamed protein. Protein 204 is identified as complement receptor CR2-C3d, 801 as YAP1 protein, 803 as antitrypsin polymer, 1505 as PRO0684, 2013 and 3010 as proapolipoprotein, 2205 as USP48, 2403 as vitamin D binding protein, 3009 as complement component 4A preprotein, 3105 as immunoglobulin lambda chain, 3205 as transthyretin, 4002 as Ras-related protein Ral-A, 4204 as beta actin, 5202 and 7104 as apolipoprotein L1, 6704 as alpha 2 macroglobulin precursor, 7103 as complement component 3 precursor, 8006 as testis-specific protein Y, 8101 as transferrin, 9001 as (Alpha-Oxy, Beta-(C112gdeoxy T-State Human Hemoglobin, and 9003 as human hemoglobin. 4. Immune protein CR2-C3d, which acts against microbes and pathogenic organisms, and Antitrypsin(803, which is secreted with inflammatory response in the lungs, were increased by more than 200% after the administration of herbal acupuncture. 5

  17. 三维片上网络拓扑结构研究综述%Survey on Topologies of Three-Dimensional Network on Chip

    Institute of Scientific and Technical Information of China (English)

    张大坤; 宋国治; 王莲莲; 黄翠

    2015-01-01

    Three-dimensional network on chip (3D NoC) is developed based on three-dimensional integrated circuit (3D IC), system on chip (SoC) and two-dimensional network on chip (2D NoC). 3D NoC is mainly used to solve the problems such as communication bottleneck of highly integrated chips. It has attracted great attention from both aca-demia and industry at home and abroad. 3D NoC topology structure reflects the layout and connectivity of communi-cations node in the chip, which is crucial for the performance of 3D chip. This paper introduces 2D NoC, the evolu-tion from 2D NoC to 3D NoC, the advantages and problems of adopting 3D NoC and the key technical issues which can be solved by 3D NoC, and analyzes the overall development of 3D NoC. 3D topology is one of the key prob-lems in the design of 3D NoC. This paper mainly studies the different classification methods for 3D NoC topology and divides 3D NoC topologies into 9 categories in terms of communication, then gives a thorough study of 3D NoC topology structures with comparison and analysis of the characteristics for each topology structure. Finally, this paper indicates the possible future research development of 3D NoC topology.%三维片上网络(three-dimensional network on chip ,3D NoC)是在三维集成电路(three-dimensional integrated circuit,3D IC)、片上系统(system on chip,SoC)和二维片上网络(two-dimensional network on chip,2D NoC)的基础上发展起来的,主要解决高集成度芯片通信瓶颈等问题,已引起国内外学术界和产业界的高度重视。3D NoC拓扑结构体现了通信节点在芯片中的布局与连接,对三维芯片性能起决定性作用。简介了2D NoC、2D NoC到3D NoC的演变、3D NoC的优点与存在的问题以及3D NoC解决的关键技术问题,分析了3D NoC总体发展状况。三维拓扑结构是3D NoC设计中的关键问题之一,重点研究了3D NoC拓扑结构的分类方法,从通信角度将3D No

  18. Comparison of clinically used shade guide systems with color range of natural teeth%三种牙科比色板与天然牙色度的比较分析

    Institute of Scientific and Technical Information of China (English)

    葛起敏; 张富强

    2008-01-01

    Objective To analyze the limitation of currently used shade guide systems comparing with color range of nature teeth. Methods Digital pictures of shade guide systems A (VITAPAN Classic), B(VINTAGE Halo), C(3D-MASTER), and 322 central incisors were taken under the same condition as light source of D65 with the observation method of d/0°. The data obtained from nature tooth color were compared with the color range of three shade guide systems mentioned above in items of L*a*b*/C* H°. Results The normal chroma value (95%) of the natural teeth were L* 61. 631-73. 250, a* - 0.719-1. 879,and b* 8.701-17.790. Natural tooth colors were different from those of the shade guide system A which color range was narrower, short of red hue, higher values, and unevenly distribution of saturation. On the other hand, the range of red hue increased in shade guide system B while its saturation was slightly high. The color range of shade guide system C was greatest among the three shade guide systems. The saturation and value of shade guide system C covered all varieties of nature teeth measured in this research, but it still lacked red hue comparing to the nature teeth. Conclusions Comparing the color range of nature teeth, the shade guide systems used in clinic have uneven hue distribution and cannot cover all colors of nature teeth. Generally, all the shade guide systems are lack of the hues which are named under the category of red tone.%目的 通过测量天然牙的色度参数范围,并与三种常用比色板的色度参数范围进行比较,分析目前常用的牙科比色板存在的局限. 方法 使用数码照相机在D65光源的非球形漫射照明观测方式下拍摄比色板A(VITAPAN Classic)、B(VINTAGE Halo)、C(3D-MASTER)和上颌天然中切牙322颗,获得天然牙和3种比色板的色度参数范围并进行比较. 结果 天然牙色度参数95%正常值的范围分别如下:明度(L*)为61.631~73.250,红绿色品(±a*)为-0.719~1.879,

  19. Maternal antibodies: clinical significance, mechanism of interference with immune responses, and possible vaccination strategies

    Directory of Open Access Journals (Sweden)

    Stefan eNiewiesk

    2014-09-01

    Full Text Available Neonates have an immature immune system which cannot adequately protect against infectious diseases. Early in life, immune protection is accomplished by maternal antibodies transferred from mother to offspring. However, decaying maternal antibodies inhibit vaccination as is examplified by the inhibition of seroconversion after measles vaccination. This phenomenon has been described in both human and veterinary medicine and is independent of the type of vaccine being used. This review will discuss the use of animal models for vaccine research. I will review clinical solutions for inhibition of vaccination by maternal antibodies, and the testing and development of potentially effective vaccines. These are based on new mechanistic insight about the inhibitory mechanism of maternal antibodies. Maternal antibodies inhibit the generation of antibodies whereas the T cell response is usually unaffected. B cell inhibition is mediated through a cross-link between B-cell receptor (BCR with the Fcg receptor IIB (FcgRIIB by a vaccine-antibody complex. In animal experiments, this inhibition can be partially overcome by injection of a vaccine-specific monoclonal IgM antibody. IgM stimulates the B-cell directly through cross-linking the BCR via complement protein C3d and antigen to the complement receptor 2 (CR2 signaling complex. In addition, it was shown that interferon alpha binds to the CD21 chain of CR2 as well as the interferon receptor and that this dual receptor usage drives B cell responses in the presence of maternal antibodies. In lieu of immunizing the infant the concept of maternal immunization as a strategy to protect neonates has been proposed. This approach would still not solve the question of how to immunize in the presence of maternal antibodies but would defer the time of infection to an age where infection might not have such a detrimental outcome as in neonates. I will review successful examples and potential challenges of implementing

  20. Structural Basis for Simvastatin Competitive Antagonism of Complement Receptor 3.

    Science.gov (United States)

    Jensen, Maria Risager; Bajic, Goran; Zhang, Xianwei; Laustsen, Anne Kjær; Koldsø, Heidi; Skeby, Katrine Kirkeby; Schiøtt, Birgit; Andersen, Gregers R; Vorup-Jensen, Thomas

    2016-08-12

    The complement system is an important part of the innate immune response to infection but may also cause severe complications during inflammation. Small molecule antagonists to complement receptor 3 (CR3) have been widely sought, but a structural basis for their mode of action is not available. We report here on the structure of the human CR3 ligand-binding I domain in complex with simvastatin. Simvastatin targets the metal ion-dependent adhesion site of the open, ligand-binding conformation of the CR3 I domain by direct contact with the chelated Mg(2+) ion. Simvastatin antagonizes I domain binding to the complement fragments iC3b and C3d but not to intercellular adhesion molecule-1. By virtue of the I domain's wide distribution in binding kinetics to ligands, it was possible to identify ligand binding kinetics as discriminator for simvastatin antagonism. In static cellular experiments, 15-25 μm simvastatin reduced adhesion by K562 cells expressing recombinant CR3 and by primary human monocytes, with an endogenous expression of this receptor. Application of force to adhering monocytes potentiated the effects of simvastatin where only a 50-100 nm concentration of the drug reduced the adhesion by 20-40% compared with untreated cells. The ability of simvastatin to target CR3 in its ligand binding-activated conformation is a novel mechanism to explain the known anti-inflammatory effects of this compound, in particular because this CR3 conformation is found in pro-inflammatory environments. Our report points to new designs of CR3 antagonists and opens new perspectives and identifies druggable receptors from characterization of the ligand binding kinetics in the presence of antagonists. PMID:27339893

  1. Molecular analysis of three Ljungan virus isolates reveals a new, close-to-root lineage of the Picornaviridae with a cluster of two unrelated 2A proteins.

    Science.gov (United States)

    Johansson, Susanne; Niklasson, Bo; Maizel, Jacob; Gorbalenya, Alexander E; Lindberg, A Michael

    2002-09-01

    Ljungan virus (LV) is a suspected human pathogen recently isolated from bank voles (Clethrionomys glareolus). In the present study, it is revealed through comparative sequence analysis that three newly determined Swedish LV genomes are closely related and possess a deviant picornavirus-like organization: 5' untranslated region-VP0-VP3-VP1-2A1-2A2-2B-2C-3A-3B-3C-3D-3' untranslated region. The LV genomes and the polyproteins encoded by them exhibit several exceptional features, such as the absence of a predicted maturation cleavage of VP0, a conserved sequence determinant in VP0 that is typically found in VP1 of other picornaviruses, and a cluster of two unrelated 2A proteins. The 2A1 protein is related to the 2A protein of cardio-, erbo-, tescho-, and aphthoviruses, and the 2A2 protein is related to the 2A protein of parechoviruses, kobuviruses, and avian encephalomyelitis virus. The unprecedented association of two structurally different 2A proteins is a feature never previously observed among picornaviruses and implies that their functions are not mutually exclusive. Secondary polyprotein processing of the LV polyprotein is mediated by proteinase 3C (3C(pro)) possessing canonical affinity to Glu and Gln at the P1 position and small amino acid residues at the P1' position. In addition, LV 3C(pro) appears to have unique substrate specificity to Asn, Gln, and Asp and to bulky hydrophobic residues at the P2 and P4 positions, respectively. Phylogenetic analysis suggests that LVs form a separate division, which, together with the Parechovirus genus, has branched off the picornavirus tree most closely to its root. The presence of two 2A proteins indicates that some contemporary picornaviruses with a single 2A may have evolved from the ancestral multi-2A picornavirus.

  2. Molecular Characterization and SYBR Green Ⅰ-Based Quantitative PCR for Duck Hepatitis Virus Type 1

    Institute of Scientific and Technical Information of China (English)

    LUO Yu-jun; ZHANG Gui-hong; XU Xiao-qin; CHEN Jian-hong; LIAO Ming

    2008-01-01

    To determine the genomic sequence of a duck hepatitis virus type 1 (DHV-1) strain,real-time quantitative polyrnerase chain reaction (RTQ-PCR) assay based on SYBR Green Ⅰ technology was developed to target 3D gene of DHV-1.Comparative sequence analysis showed that the genome has a typical picornarivus genetic organization,and strain DHV-1 R genetic organaiztion is 5' untranslated region (UTR)-VPO-VP3-VP1-2A1-2A2-2B-2C-3A-3B-3C-3D-3' UTR,DHV-1 R has close relationship with Parechovirus,and has 95.1-99.1% nucleotide sequence identity with other DHV-1 strains.Based on the DHV-1 sequences in GenBank,three pairs of specific primers were designed to amplify DHV-1 using real-time PCR.The results showed that real-time PCR Tm value is 85.6℃ and the real-time PCR provides a broad dynamic range,detecting from 102 to 109 copies of DHV-1 cDNA per reaction.No cross-reactions were found in specimens containing DPV,AIV and NDV.It is concluded that DHV-1 belongs to a new group of the family Picornaviridae that may form a separate genus most closely related to the genus Parechovirus.All results showed that the real-time PCR has high sensitivity and specificity to detect DHV-1 using SYBR Green Ⅰ dissociation curve analysis,isolates can be distinguished by their melting temperature.These methods are rapid,sensitive,and reliable,and can be readily adapted for detection of DHV-1 from other clinical samples.

  3. Development and validation of an Eulerian model towards the simulation of fuel injection in internal combustion engines; Developpement et validation d'un modele eulerien en vue de la simulation des jets de carburants dans les moteurs a combustion interne

    Energy Technology Data Exchange (ETDEWEB)

    Truchot, B.

    2005-12-15

    The objective of this work is to develop an Eulerian two phase model to improve the prediction of fuel injection in internal combustion engines, particularly the dense liquid zone close to the nozzle. Lagrangian models, usually used in engine simulations, are based on the assumption of dispersed two phase flows with low liquid volume fraction, which is not fulfilled in the case of direct injection engine technology. Different Eulerian approaches are available in the literature. Physical phenomena that occur near the nozzle and characteristics of each model lead to the choice of a two fluids two pressures model. Several open terms appear in the equations of the model: exchange between the two phases and turbulent correlations. Closures of exchange terms are based on the spherical droplets hypothesis while a RANS approach is adopted to close turbulent correlations. This model has been integrated in the IFP CFD code, IFP-C3D. Several numerical tests and analytical validations (for single and two phase flows) have been then carried out in order to check the correct implementation of equations and the predictivity of the model and closures. Modifications in the turbulent model of the gas have required validations in both the gas phase (flow behind a sudden enlargement) and the liquid phase (pure liquid injection). A two phase mixing layer has been then used to validate the whole model. Finally, injection tests have been achieved under realistic conditions (similar to those encountered in automotive engines) in order to check the feasibility of engine computations using the developed Eulerian approach. These tests have also allowed to check the compatibility of this approach with the specificities of engine simulations (especially mesh movement). (author)

  4. 猪O型口蹄疫病毒温度敏感突变株部分基因的PCR扩增及序列分析%PCR Amplification and Sequence Analysis of Partial Gene from Temperature-sensitive mutant of Foot-and-Mouth Disease Virus Type O in Swine

    Institute of Scientific and Technical Information of China (English)

    刘航; 杨晓燕; 侯相民; 田永强

    2012-01-01

    根据O型FMDV全基因组序列设计引物,通过PCR扩增得到目的基因,并对猪O型FMDV的强弱毒株基因进行克隆与序列分析.结果表明:扩增得到的O型口蹄疫病毒温度敏感株L、P1、P2、P3 (3C、3D)区目的基因片段大小分别为603、2208、1464、639、1410 bp,与预期相符.各区序列拼接后与野生型猪O型FMDV序列比对,两者同源性为88%.%In order to analyse the differences between wild type strain and temperature-sensitive mutation strain of foot-and-mouth disease virus (FMDV) type 0 in swine, five pairs of primer were designed according to complete genome sequences of the FMDV type 0 in the GenBank, and the gene of virulent and attenuated strain of FMDV type 0 in swine was cloned by PCR amplification and its sequence was analyzed. The results showed that the predicted fragments were obtained by RT-PCR from L, P1,P2 and P3(3C, 3D) area of temperature-sensitive strain of FMDV type 0, with fragment size of 603 kb, 2 208 kb, 1 464 kb, 639 kb and 1 410 kb, respectively. After sequence assembly, nucleotide sequence alignment results showed that the homology between wild type strain and temperature-sensitive mutation strain of FMDV type O was 88%.

  5. Classical Complement Pathway Activation in the Kidneys of Women With Preeclampsia.

    Science.gov (United States)

    Penning, Marlies; Chua, Jamie S; van Kooten, Cees; Zandbergen, Malu; Buurma, Aletta; Schutte, Joke; Bruijn, Jan Anthonie; Khankin, Eliyahu V; Bloemenkamp, Kitty; Karumanchi, S Ananth; Baelde, Hans

    2015-07-01

    A growing body of evidence suggests that complement dysregulation plays a role in the pathogenesis of preeclampsia. The kidney is one of the major organs affected in preeclampsia. Because the kidney is highly susceptible to complement activation, we hypothesized that preeclampsia is associated with renal complement activation. We performed a nationwide search for renal autopsy material in the Netherlands using a computerized database (PALGA). Renal tissue was obtained from 11 women with preeclampsia, 25 pregnant controls, and 14 nonpregnant controls with hypertension. The samples were immunostained for C4d, C1q, mannose-binding lectin, properdin, C3d, C5b-9, IgA, IgG, and IgM. Preeclampsia was significantly associated with renal C4d-a stable marker of complement activation-and the classical pathway marker C1q. In addition, the prevalence of IgM was significantly higher in the kidneys of the preeclamptic women. No other complement markers studied differed between the groups. Our findings in human samples were validated using a soluble fms-like tyrosine kinase 1 mouse model of preeclampsia. The kidneys in the soluble fms-like tyrosine kinase 1-injected mice had significantly more C4 deposits than the control mice. The association between preeclampsia and renal C4d, C1q, and IgM levels suggests that the classical complement pathway is involved in the renal injury in preeclampsia. Moreover, our finding that soluble fms-like tyrosine kinase 1-injected mice develop excess C4 deposits indicates that angiogenic dysregulation may play a role in complement activation within the kidney. We suggest that inhibiting complement activation may be beneficial for preventing the renal manifestations of preeclampsia.

  6. Influence of time interval between surgery and radiotherapy on tumor regrowth

    Energy Technology Data Exchange (ETDEWEB)

    Cividalli, A.; Ceciarelli, F.; Tirindelli Danesi, D. [ENEA, Rome (Italy). Casaccia Research Center, Section of Toxicology and Biomedical Sciences; Creton, G. [Clinica Villa Flaminia, Rome (Italy). Dept. of Radiotheraphy; Stringari, L.; Benassi, M. [Regina Elena Cancer Institute, Rome (Italy). Division of Medical Physics

    2005-03-15

    In order to evaluate the influence of time intervals between tumor cell injection and radiotherapy on tumor control and regrowth after surgery, we performed two kinds of experiments on C3D2F1 mice bearing a mammary carcinoma inoculated in the foot or leg. 1. experiment: tumor in foot. End point: Tumor Control Probability (TCP). Single dose radiation treatments (RT) were administered at different period times from injection time of tumor cells (day 1). 1. group: unirradiated control, 2. group: RT on day 2 (TCP50 29{+-}2.1 Gy), 3. group: RT on day 7 (TCP 52.5{+-}2.9 Gy), 4. group: RT on day 12 (TCP50 61.9{+-}2.4 Gy). 2. experiment: tumor in leg. End point: percentage of tumor regrowth. Mice were randomly assigned to three groups: 1. control group (tumor growth in all mice), 2. surgical excision of macroscopically evident tumor on day 7-9 from injection (tumor regrowth in 85% of mice), 3. as the previous group plus 30 Gy radiation treatment within 24 hours from excision (tumor regrowth in 33% of cases). The radiation dose was selected on the basis of TCP50 observed in the 1. experiment for mice with sub-clinical disease. These data indicate that the radiation dose able to control 50% of tumors increases with the time interval between tumor cells injection and RT. A short time interval between surgery and RT should increase the probability of local control, supporting the rationale of intraoperative radiation therapy (IORT) as adjuvant therapy after surgical resection, when subclinical residual cells are suspected.

  7. Study on the cooperation influence of stabilizers on soft-serve ice cream quality%4种稳定剂对软冰淇淋品质协同作用研究

    Institute of Scientific and Technical Information of China (English)

    刘梅森; 何唯平; 陈胜利

    2005-01-01

    考察了瓜胶(A)、CMC(B)、魔芋胶(C)、黄原胶(D)在软冰淇淋中的作用,通过正交实验,对瓜胶、CMC、魔芋胶、黄原胶在软冰淇淋浆料黏度及软冰淇淋硬度、膨胀率、抗融性等方面的影响进行研究,结果表明:黄原胶对软冰淇淋黏度的影响最大,CMC影响最小,其最佳组合为A1B3C3D3;在软冰淇淋膨胀率方面,瓜胶的影响最大,黄原胶的影响最小,最佳组合为A3B3C2D1;在软冰淇淋硬度方面,黄原胶的影响最大,最佳组合为A1B1C1D1,瓜胶影响最小;在软冰淇淋抗融性方面,瓜胶最有利于抗溶性提高,魔芋胶对抗溶性改善最小,最佳组合为A2B1C2D3.所以瓜胶对膨化率和抗溶性影响最大,对硬度影响最小;黄原胶对黏度和硬度影响最大,但对膨化率影响最小;CMC对黏度影响最小;魔芋胶对抗溶性影响最小.

  8. Identification of Eight Different Isoforms of the Glucocorticoid Receptor in Guinea Pig Placenta: Relationship to Preterm Delivery, Sex and Betamethasone Exposure.

    Directory of Open Access Journals (Sweden)

    Zarqa Saif

    Full Text Available The placental glucocorticoid receptor (GR is central to glucocorticoid signalling and for mediating steroid effects on pathways associated with fetal growth and lung maturation but the GR has not been examined in the guinea pig placenta even though this animal is regularly used as a model of preterm birth and excess glucocorticoid exposure. Guinea pig dams received subcutaneous injections of either vehicle or betamethasone at 24 and 12 hours prior to preterm or term caesarean-section delivery. At delivery pup and organ weights were recorded. Placentae were dissected, weighed and analysed using Western blot to examine GR isoform expression in nuclear and cytoplasmic extracts. A comparative examination of the guinea pig GR gene identified it is capable of producing seven of the eight translational GR isoforms which include GRα-A, C1, C2, C3, D1, D2, and D3. GRα-B is not produced in the Guinea Pig. Total GR antibody identified 10 specific bands from term (n = 29 and preterm pregnancies (n = 27. Known isoforms included GRγ, GRα A, GRβ, GRP, GRA and GRα D1-3. There were sex and gestational age differences in placental GR isoform expression. Placental GRα A was detected in the cytoplasm of all groups but was significantly increased in the cytoplasm and nucleus of preterm males and females exposed to betamethasone and untreated term males (KW-ANOVA, P = 0.0001, P = 0.001. Cytoplasmic expression of GRβ was increased in female preterm placentae and preterm and term male placentae exposed to betamethasone (P = 0.01. Nuclear expression of GRβ was increased in all placentae exposed to betamethasone (P = 0.0001. GRα D2 and GRα D3 were increased in male preterm placentae when exposed to betamethasone (P = 0.01, P = 0.02. The current data suggests the sex-specific placental response to maternal betamethasone may be dependent on the expression of a combination of GR isoforms.

  9. A novel approach to inhibit HIV-1 infection and enhance lysis of HIV by a targeted activator of complement

    Directory of Open Access Journals (Sweden)

    Huang Liuyu

    2009-08-01

    Full Text Available Abstract Background The complement system is one of the most potent weapons of innate immunity. It is not only a mechanism for direct protection against invading pathogens but it also interacts with the adaptive immunity to optimize the pathogen-specific humoral and cellular defense cascades in the body. Complement-mediated lysis of HIV is inefficient but the presence of HIV particles results in complement activation by the generation of many C3-fragments, such as C3dg and C3d. It has been demonstrated that activation of complement can enhance HIV infection through the binding of special complement receptor type 2 expression on the surface of mature B cells and follicular dendritic cells. Presentation of the hypothesis Previous studies have proven that the complement-mediated antibody-dependent enhancement of HIV infection is mediated by the association of complement receptor type 2 bound to the C3 fragment and deposited on the surface of HIV virions. Thus, we hypothesize that a new activator of complement, consisting of a target domain (C3-binding region of complement receptor type 2 linked to a complement-activating human IgG1 Fc domain (CR2-Fc, can target and amplify complement deposition on HIV virions and enhance the efficiency of HIV lysis. Testing the hypothesis Our hypothesis was tested using cell-free HIV-1 virions cultivated in vitro and assessment of virus opsonization was performed by incubating appropriate dilutions of virus with medium containing normal human serum and purified CR2-Fc proteins. As a control group, viruses were incubated with normal human serum under the same conditions. Virus neutralization assays were used to estimate the degree of CR2-Fc-enhanced lysis of HIV compared to untreated virus. Implications of the hypothesis The targeted complement activator, CR2-Fc, can be used as a novel approach to HIV therapy by abrogating the complement-enhanced HIV infection of cells.

  10. Epstein-Barr virus receptor expression on human CD8+ (cytotoxic/suppressor) T lymphocytes.

    Science.gov (United States)

    Sauvageau, G; Stocco, R; Kasparian, S; Menezes, J

    1990-02-01

    In 1977 we showed that cells of a human lymphocytic leukaemia-derived T line (Molt-4) have receptors for Epstein-Barr virus (EBV). More recently, EBV-positive human T cell lymphomas have been recognized and human T cell lines containing the EBV genome have been established in vitro. To understand better the interaction of EBV with T cells, we decided to determine first whether human peripheral blood T lymphocytes express receptors for EBV. Using flow cytometry we examined the binding of both lymphocyte-transforming (B95-8) and non-transforming (P3HR-1) strains of EBV to T lymphocyte subpopulations, using a double labelling technique with T cell-specific phycoerythrinated monoclonal antibodies (Leu 2a) and fluoresceinated viral preparation. Our results suggest that, in general, about 50% of the CD8+ (or suppressor/cytotoxic) T cell subpopulation from both EBV-seropositive and -seronegative individuals can bind EBV. EBV receptor expression on these T cells was about 10 and 51 times less than that on Molt-4 and Raji (an EBV receptor-positive B cell line) cells, respectively. The specificity of this binding was demonstrated by the inhibition of attachment of viral preparations preincubated with a monoclonal antibody directed against the viral ligand (gp240/350), and by preincubating these target T cells with unlabelled virus. We were unable to detect EBV-induced antigens in infected T cells, suggesting that, as in Molt-4 cells, virus internalization may not occur in fresh T cells and/or that the virus receptor may not be completely functional. We were also unable to detect C3d (or CR2) receptors on these T cells, or to inhibit virus attachment by treating the targets with an anti-CR2 monoclonal antibody (OKB7), suggesting that the EBV receptor on CD8+ peripheral blood lymphocytes is different from that on B cells. PMID:2155291

  11. The dual role of complement in the progression of renal disease in NZB/W F(1) mice and alternative pathway inhibition.

    Science.gov (United States)

    Sekine, Hideharu; Ruiz, Phillip; Gilkeson, Gary S; Tomlinson, Stephen

    2011-10-01

    Complement plays a dual role in the progression of systemic lupus erythematosus since it has important protective functions, such as the clearance of immune complexes and apoptotic cells, but is also a mediator of renal inflammation. To investigate this balance in a clinically relevant setting, we investigated how targeted inhibition of all complement pathways vs. targeted inhibition of only the alternative pathway impacts immune and therapeutic outcomes in NZB/W F(1) mice. Following onset of proteinuria, mice were injected twice weekly with CR2-fH (inhibits alternative pathway), CR2-Crry (inhibits all pathways at C3 activation step), sCR2 (C3d targeting vehicle) or saline. Sera were analyzed every 2 weeks for anti-dsDNA antibody levels, and urinary albumin excretion was determined. Kidneys were collected for histological evaluation at 32 weeks. Compared to the control group, all CR2-fH, CR2-Crry and sCR2 treated groups showed significantly reduced serum anti-dsDNA antibody levels and strong trends towards reduced glomerular IgG deposition levels. Glomerular C3 deposition levels were also significantly reduced in all three-treated groups. However, significant reductions of disease activity (albuminuria and glomerulonephritis) were only seen in the CR2-fH treated group. These data highlight the dual role played by complement in the pathogenesis of lupus, and demonstrate a benefit of selectively inhibiting the alternative complement pathway, presumably because of protective contributions from the classical and/or lectin pathways. The sCR2 targeting moiety appears to be contributing to therapeutic outcome via modulation of autoimmunity. Furthermore, these results are largely consistent with our previous data using the MRL/lpr lupus model, thus broadening the significance of these findings. PMID:22000720

  12. Isolating the Epstein-Barr virus gp350/220 binding site on complement receptor type 2 (CR2/CD21).

    Science.gov (United States)

    Young, Kendra A; Chen, Xiaojiang S; Holers, V Michael; Hannan, Jonathan P

    2007-12-14

    Complement receptor type 2 (CR2/CD21) is essential for the attachment of Epstein-Barr virus (EBV) to the surface of B-lymphocytes in an interaction mediated by the viral envelope glycoprotein gp350. The heavily glycosylated structure of EBV gp350 has recently been elucidated by x-ray crystallography, and the CR2 binding site on this protein has been characterized. To identify the corresponding gp350 binding site on CR2, we have undertaken a site-directed mutagenesis study targeting regions of CR2 that have previously been implicated in the binding of CR2 to the C3d/C3dg fragments of complement component C3. Wild-type or mutant forms of CR2 were expressed on K562 cells, and the ability of these CR2-expressing cells to bind gp350 was measured using flow cytometry. Mutations directed toward the two N-terminal extracellular domains of CR2 (SCR1-2) reveal that a large contiguous surface of CR2 SCR1-2 is involved in gp350 binding, including a number of positively charged residues (Arg-13, (Arg-28, (Arg-36, Lys-41, Lys-57, Lys-67, and Arg-83). These data appear to complement the CR2 binding site on gp350, which is characterized by a preponderance of negative charge. In addition to identifying the importance of charge in the formation of a CR2-gp350 complex, we also provide evidence that both SCR1 and SCR2 make contact with gp350. Specifically, two anti-CR2 monoclonal antibodies, designated as monoclonal antibodies 171 and 1048 whose primary epitopes are located within SCR2, inhibit binding of wild-type CR2 to EBV gp350; with regard to SCR1, both K562 cells expressing an S15P mutation and recombinant S15P CR2 proteins exhibit diminished gp350 binding. PMID:17925391

  13. The flow field in a high aspect ratio cooling duct with and without one heated wall

    Science.gov (United States)

    Rochlitz, Henrik; Scholz, Peter; Fuchs, Thomas

    2015-12-01

    The flow in a high aspect ratio generic cooling duct is described for different Reynolds numbers and for adiabatic as well as non-adiabatic conditions. The Reynolds number is varied in a range from 39,000 to 111,000. The generic cooling duct facility allows for applying a constant temperature on the duct's lower wall, and it ensures having well-defined boundary conditions. The high-quality, optical noninvasive measurement methods, namely Particle Image Velocimetry (2C2D-PIV, i.e., two velocity components in a plane), Stereo Particle Image Velocimetry (3C2D-PIV, i.e., three velocity components in a plane) and Volumetric Particle Tracking Velocimetry (3C3D-PTV, i.e., three velocity components in a volume), are used to characterize the flow in detail. Pressure transducers are installed for measuring the pressure losses. The repeatability and the validity of the data are discussed in detail. For that purpose, modifications in the test facility and in the experimental setup as well as comparisons between the different measurement methods are given. A focus lies on the average velocity distribution and on the turbulent statistics. The longitudinal velocity profile is analyzed in detail for Reynolds number variations. Secondary flows are identified with velocities of two orders of magnitude smaller than the longitudinal velocity. Reynolds stress distributions are given for several different cases. The Reynolds number dependency of overline{u'^2} and overline{v'^2} is shown, and a comparison between the adiabatic and the heated case is given. overline{u'^2} changes significantly when the lower wall heat flux is applied, whereas overline{v'^2} and overline{u'v'} almost stay constant.

  14. Expression of CR2/EBV receptors on human thymocytes detected by monoclonal antibodies.

    Science.gov (United States)

    Tsoukas, C D; Lambris, J D

    1988-08-01

    The biologic effects of the third component of complement, C3, are mediated via receptors which specifically bind the enzymatic degradation products resulting from the cleavage of C3. One of the products, C3d, has been associated with binding to the second complement receptor CR2 (CD21). This receptor, which is identical to the receptor for Epstein-Barr virus (EBV), has been primarily found on cells of the B lineage, but not on mature T cells or other cells of erythroid or myeloid lineages. In the present investigation, we report the presence of CR2 on human thymocytes. Indirect immunofluorescence analysis employing monoclonal anti-CR2 antibodies revealed a range of thymocyte reactivity from 15% to 63% in thirteen experiments using cells of different donors. Reactivity was always greater with the monoclonal anti-CR2 (CD21) antibody HB-5 than with two other antibodies which recognize distinct epitopes on the CR2 molecule. Two-color immunofluorescence analysis indicated that the brightest of the HB-5-stained thymocytes also reacted with the monoclonal anti-CD1 antibody T6 (immature thymocyte marker) while some of the duller HB-5-staining cells reacted with the monoclonal anti-CD3 antibody Leu-4 (mature thymocyte marker). Immunoprecipitation of CR2 on thymocytes with antibody HB-5 and polyacrylamide gel electrophoretic analysis revealed a protein of 145 kDa molecular mass which is consistent with the size of CR2 found on B lymphocytes. These findings raise several questions regarding the biologic role of CR2-EBV receptor on cells of the T lineage. PMID:2970972

  15. Novel autostereoscopic single-user displays with user interaction

    Science.gov (United States)

    Hopf, Klaus; Chojecki, Paul; Neumannn, Frank; Przewozny, David

    2006-10-01

    This paper describes recent advances in the field of autostereoscopic display development and introduces an appropriate integration of a novel user interaction technology. Beside technical aspects of the developed autostereoscopic display technology, the paper includes topics of our video-based interaction technique and introduces promising applications of autostereoscopic single user displays. Based on results of the European ATTEST project, the Fraunhofer Institute for Telecommunications (HHI) has developed the Free2C 3D display technology, which provides free positioning of a single viewer. The optics of the Free2C displays is designed such that extremely low crosstalk, excellent color reproduction and high brightness are achieved. Simple and intuitive interaction is a requirement for multi-modal 3D displays. For this reason, a novel technology has been integrated into the control console that can recognize a persons' hand and its gestures. Displayed 3D objects floating in front of the screen can be rotated by simple gestures and virtual buttons can be pressed by pointing at them (virtual 3D touch screen). Several applications are currently used by customers and have been presented at trade shows, exhibitions and showrooms. Feasible applications are based on computer generated content, live video created by stereoscopic cameras and films stored on hard disk. Immersive media presentations are one promising application for attractive stereoscopic representations. The Free2C Kiosk and the 3D Media Center combine a high-resolution autostereoscopic 3D display with a video-based hand-gesture recognition device for direct manipulation of virtual 3D objects floating in front of the screen.

  16. Role of complement receptor 1 (CR1; CD35) on epithelial cells: A model for understanding complement-mediated damage in the kidney.

    Science.gov (United States)

    Java, Anuja; Liszewski, M Kathryn; Hourcade, Dennis E; Zhang, Fan; Atkinson, John P

    2015-10-01

    The regulators of complement activation gene cluster encodes a group of proteins that have evolved to control the amplification of complement at the critical step of C3 activation. Complement receptor 1 (CR1) is the most versatile of these inhibitors with both receptor and regulatory functions. While expressed on most peripheral blood cells, the only epithelial site of expression in the kidney is by the podocyte. Its expression by this cell population has aroused considerable speculation as to its biologic function in view of many complement-mediated renal diseases. The goal of this investigation was to assess the role of CR1 on epithelial cells. To this end, we utilized a Chinese hamster ovary cell model system. Among our findings, CR1 reduced C3b deposition by ∼ 80% during classical pathway activation; however, it was an even more potent regulator (>95% reduction in C3b deposition) of the alternative pathway. This inhibition was primarily mediated by decay accelerating activity. The deposited C4b and C3b were progressively cleaved with a t½ of ∼ 30 min to C4d and C3d, respectively, by CR1-dependent cofactor activity. CR1 functioned intrinsically (i.e, worked only on the cell on which it was expressed). Moreover, CR1 efficiently and stably bound but didn't internalize C4b/C3b opsonized immune complexes. Our studies underscore the potential importance of CR1 on an epithelial cell population as both an intrinsic complement regulator and an immune adherence receptor. These results provide a framework for understanding how loss of CR1 expression on podocytes may contribute to complement-mediated damage in the kidney.

  17. Radioimmunoassay of milk progesterone to monitor reproductive performance in smallholder dairy herds in Indonesia

    International Nuclear Information System (INIS)

    Studies involving 260 Friesian cows from three different locations were conducted to monitor the reproductive performance in small dairy herds in Indonesia by using milk progesterone RIA. In the first study 90 post-partum cows at three locations (Surabaya, Grati and Puspo) were used to investigate post-partum ovarian function. The highest incidence of cows not showing oestrus up to 80 days post-partum, with progesterone profiles less than 0.75 ng/mL, was found in Puspo (63.3%), compared with 10% in Surabaya and 20% in Grati. The incidence of cows with silent heat and oestrus without ovulation was 13.3 and 3.3% in Surabaya, 16.7 and 6.7% in Grati, and 23.3 and 0% in Puspo. There was no significant difference (P>0.05) between the lengths of oestrous cycles at the three different locations. In the second study, using 120 cows for investigating confirmation of oestrus at AI, 69.7% of cows inseminated during the follicular phase had become pregnant, compared with 16.1% of cows inseminated during the luteal phase. The incidence of long luteal phases which included embryonic death was 13.4%. The accuracy of pregnancy diagnosis based on progesterone concentrations at day 22 was 77% and was lower than that at day 29 (88%). In the third study, cows in Subgroups 3A and 3B had cystic ovaries and were treated with prostaglandin F2α by either intramuscular (3A) or intrauterine (3B) routes. Pregnancy rates were 50 and 40%, respectively. Cows in Subgroups 3C, 3D and 3E had inactive ovaries and were treated with intravaginal application of MPA sponges (3C), PRID (3D) or PRID followed by LH injection (3E). The pregnancy rates were 30, 40 and 60%, respectively. (author). 10 refs, 6 tabs

  18. Effects of Repeated Complement Activation Associated with Chronic Treatment of Cynomolgus Monkeys with 2'-O-Methoxyethyl Modified Antisense Oligonucleotide.

    Science.gov (United States)

    Shen, Lijiang; Engelhardt, Jeffrey A; Hung, Gene; Yee, Jenna; Kikkawa, Rie; Matson, John; Tayefeh, Bryan; Machemer, Todd; Giclas, Patricia C; Henry, Scott P

    2016-08-01

    The effects of repeated complement activation in cynomolgus monkeys after chronic antisense oligonucleotide (ASO) treatment were evaluated by using ISIS 104838, a representative 2'-O-methoxyethyl (2'-MOE) modified ASO. The treatment was up to 9 months with a total weekly dose of 30 mg/kg, given either as daily [4.3 mg/kg/day, subcutaneous (s.c.) injection] or once weekly [30 mg/kg, either as s.c. injection or 30-min intravenous (i.v.) infusion]. Acute elevations of complement split products (Bb and C3a) and a transient decrease in C3 occurred after the first dose and were drug plasma concentration dependent. However, with repeated complement activation after chronic ASO treatment, there were progressive increases in basal (predose) levels of Bb and C3a, and a sustained C3 reduction in all treated groups. There was also a progressive increase in C3d-bound circulating immune complex (CIC) that was considered secondary to the C3 depletion. Evidence of vascular inflammation was observed, mostly in the liver, kidney, and heart, and correlated with severe C3 depletion and increases in plasma IgG and IgM. Vascular inflammation was accompanied by increased C3 and IgM immunereactivity in the affected vasculatures and endothelial activation markers in serum. In summary, repeated complement activations in monkeys lead to a sustained decrease in circulating C3 over time. The concomitantly increased inflammatory signals and decreased CIC clearance due to impairment of complement function may lead to vascular inflammation after chronic ASO treatment in monkeys. However, based on the known sensitivity of monkeys to ASO-induced complement activation, these findings have limited relevance to humans. PMID:27140858

  19. The dual role of complement in the progression of renal disease in NZB/W F(1) mice and alternative pathway inhibition.

    Science.gov (United States)

    Sekine, Hideharu; Ruiz, Phillip; Gilkeson, Gary S; Tomlinson, Stephen

    2011-10-01

    Complement plays a dual role in the progression of systemic lupus erythematosus since it has important protective functions, such as the clearance of immune complexes and apoptotic cells, but is also a mediator of renal inflammation. To investigate this balance in a clinically relevant setting, we investigated how targeted inhibition of all complement pathways vs. targeted inhibition of only the alternative pathway impacts immune and therapeutic outcomes in NZB/W F(1) mice. Following onset of proteinuria, mice were injected twice weekly with CR2-fH (inhibits alternative pathway), CR2-Crry (inhibits all pathways at C3 activation step), sCR2 (C3d targeting vehicle) or saline. Sera were analyzed every 2 weeks for anti-dsDNA antibody levels, and urinary albumin excretion was determined. Kidneys were collected for histological evaluation at 32 weeks. Compared to the control group, all CR2-fH, CR2-Crry and sCR2 treated groups showed significantly reduced serum anti-dsDNA antibody levels and strong trends towards reduced glomerular IgG deposition levels. Glomerular C3 deposition levels were also significantly reduced in all three-treated groups. However, significant reductions of disease activity (albuminuria and glomerulonephritis) were only seen in the CR2-fH treated group. These data highlight the dual role played by complement in the pathogenesis of lupus, and demonstrate a benefit of selectively inhibiting the alternative complement pathway, presumably because of protective contributions from the classical and/or lectin pathways. The sCR2 targeting moiety appears to be contributing to therapeutic outcome via modulation of autoimmunity. Furthermore, these results are largely consistent with our previous data using the MRL/lpr lupus model, thus broadening the significance of these findings.

  20. Isolating the Epstein-Barr virus gp350/220 binding site on complement receptor type 2 (CR2/CD21).

    Science.gov (United States)

    Young, Kendra A; Chen, Xiaojiang S; Holers, V Michael; Hannan, Jonathan P

    2007-12-14

    Complement receptor type 2 (CR2/CD21) is essential for the attachment of Epstein-Barr virus (EBV) to the surface of B-lymphocytes in an interaction mediated by the viral envelope glycoprotein gp350. The heavily glycosylated structure of EBV gp350 has recently been elucidated by x-ray crystallography, and the CR2 binding site on this protein has been characterized. To identify the corresponding gp350 binding site on CR2, we have undertaken a site-directed mutagenesis study targeting regions of CR2 that have previously been implicated in the binding of CR2 to the C3d/C3dg fragments of complement component C3. Wild-type or mutant forms of CR2 were expressed on K562 cells, and the ability of these CR2-expressing cells to bind gp350 was measured using flow cytometry. Mutations directed toward the two N-terminal extracellular domains of CR2 (SCR1-2) reveal that a large contiguous surface of CR2 SCR1-2 is involved in gp350 binding, including a number of positively charged residues (Arg-13, (Arg-28, (Arg-36, Lys-41, Lys-57, Lys-67, and Arg-83). These data appear to complement the CR2 binding site on gp350, which is characterized by a preponderance of negative charge. In addition to identifying the importance of charge in the formation of a CR2-gp350 complex, we also provide evidence that both SCR1 and SCR2 make contact with gp350. Specifically, two anti-CR2 monoclonal antibodies, designated as monoclonal antibodies 171 and 1048 whose primary epitopes are located within SCR2, inhibit binding of wild-type CR2 to EBV gp350; with regard to SCR1, both K562 cells expressing an S15P mutation and recombinant S15P CR2 proteins exhibit diminished gp350 binding.

  1. Efficacy of Targeted Complement Inhibition in Experimental C3 Glomerulopathy

    Science.gov (United States)

    Ruseva, Marieta M.; Peng, Tao; Lasaro, Melissa A.; Bouchard, Keith; Liu-Chen, Susan; Sun, Fang; Yu, Zhao-Xue; Marozsan, Andre; Wang, Yi

    2016-01-01

    C3 glomerulopathy refers to renal disorders characterized by abnormal accumulation of C3 within the kidney, commonly along the glomerular basement membrane (GBM). C3 glomerulopathy is associated with complement alternative pathway dysregulation, which includes functional defects in complement regulator factor H (FH). There is no effective treatment for C3 glomerulopathy. We investigated the efficacy of a recombinant mouse protein composed of domains from complement receptor 2 (CR2) and FH (CR2-FH) in two models of C3 glomerulopathy with either preexisting or triggered C3 deposition along the GBM. FH-deficient mice spontaneously develop renal pathology associated with abnormal C3 accumulation along the GBM and secondary plasma C3 deficiency. CR2-FH partially restored plasma C3 levels in FH-deficient mice 2 hours after intravenous injection. CR2-FH specifically targeted glomerular C3 deposits, reduced the linear C3 reactivity assessed with anti-C3 and anti-C3b/iC3b/C3c antibodies, and prevented further spontaneous accumulation of C3 fragments along the GBM. Reduction in glomerular C3d and C9/C5b-9 reactivity was observed after daily administration of CR2-FH for 1 week. In a second mouse model with combined deficiency of FH and complement factor I, CR2-FH prevented de novo C3 deposition along the GBM. These data show that CR2-FH protects the GBM from both spontaneous and triggered C3 deposition in vivo and indicate that this approach should be tested in C3 glomerulopathy. PMID:26047789

  2. Optimization of temperature and time for drying and carbonization to increase calorific value of coconut shell using Taguchi method

    Science.gov (United States)

    Musabbikhah, Saptoadi, H.; Subarmono, Wibisono, M. A.

    2016-03-01

    Fossil fuel still dominates the needs of energy in Indonesia for the past few years. The increasing scarcity of oil and gas from non-renewable materials results in an energy crisis. This condition turns to be a serious problem for society which demands immediate solution. One effort which can be taken to overcome this problem is the utilization and processing of biomass as renewable energy by means of carbonization. Thus, it can be used as qualified raw material for production of briquette. In this research, coconut shell is used as carbonized waste. The research aims at improving the quality of coconut shell as the material for making briquettes as cheap and eco-friendly renewable energy. At the end, it is expected to decrease dependence on oil and gas. The research variables are drying temperature and time, carbonization time and temperature. The dependent variable is calorific value of the coconut shell. The method used in this research is Taguchi Method. The result of the research shows thus variables, have a significant contribution on the increase of coconut shell's calorific value. It is proven that the higher thus variables are higher calorific value. Before carbonization, the average calorific value of coconut shell reaches 4,667 call/g, and a significant increase is notable after the carbonization. The optimization is parameter setting of A2B3C3D3, which means that the drying temperature is 105 °C, the drying time is 24 hours, the carbonization temperature is 650 °C and carbonization time is 120 minutes. The average calorific value is approximately 7,744 cal/g. Therefore, the increase of the coconut shell's calorific value after the carbonization is 3,077 cal/g or approximately 60 %. The charcoal of carbonized coconut shell has met the requirement of SNI, thus it can be used as raw material in making briquette which can eventually be used as cheap and environmental friendly fuel.

  3. Ares V Utilization in Support of a Human Mission to Mars

    Science.gov (United States)

    Holladay, J. B.; Jaap, J. P.; Pinson, R. M.; Creech, S. D.; Ryan, R. M.; Monk, T. S.; Baggett. K. E.; Runager, M. D.; Dux, I. J.; Hack, K. J.; Hopkins, J. M.; Brown, C. E.; Manning, T. A.

    2010-01-01

    During the analysis cycles of Phase A-Cycle 3 (PA-C3) and the follow-on 8-wk minicycle of PA-C3', the Ares V team assessed the Ares V PA-C3D configuration to the Mars Design Reference Mission as defined in the Constellation Architecture Requirements Document and further described in Mars Design Reference Architecture 5.0 (DRA 5.0) that was publicly released in July 2009. The ability to support the reference approach for the crewed Mars mission was confirmed through this analysis (7-launch nuclear thermal propulsion (NTP) architecture) and the reference chemical approach as defined in DRA 5.0 (11- or 12-launch chemical propulsion module approach). Additional chemical propulsion options were defined that utilized additional technology investments (primarily in-space cryogenic propellant transfer) that allowed for the same mission to be accomplished with 9 launches rather than the 11 or 12, as documented in DRA 5.0 and associated follow-on activities. This nine-launch chemical propulsion approach showed a unique ability to decouple the architecture from major technological developments (such as zero-boiloff technology or the development of NTP stages) and allowed for a relaxing of the infrastructure investments required to support a very rapid launch rate (30-day launch spacing as documented in DRA 5.0). As an enhancing capability, it also shows promise in allowing for and incorporating the development of a commercial market for cryogenic propellant delivery on orbit, without placing such development on the critical path of beyond low-Earth orbit exploration. The ability of Ares V to support all of the aforementioned options and discussion of key forward work that is required to fully understand the complexities and challenges presented by the Mars mission is further documented herein.

  4. A study of the C3H2 isomers and isotopologues: first interstellar detection of HDCCC

    Science.gov (United States)

    Spezzano, S.; Gupta, H.; Brünken, S.; Gottlieb, C. A.; Caselli, P.; Menten, K. M.; Müller, H. S. P.; Bizzocchi, L.; Schilke, P.; McCarthy, M. C.; Schlemmer, S.

    2016-02-01

    The partially deuterated linear isomer HDCCC of the ubiquitous cyclic carbene (c-C3H2) was observed in the starless cores TMC-1C and L1544 at 96.9 GHz, and a confirming line was observed in TMC-1 at 19.38 GHz. To aid the identification in these narrow line sources, four centimetre-wave rotational transitions (two in the previously reported Ka = 0 ladder and two new ones in the Ka = 1 ladder) and 23 transitions in the millimetre band between 96 and 272 GHz were measured in high-resolution laboratory spectra. Ten spectroscopic constants in a standard asymmetric top Hamiltonian allow the main transitions of astronomical interest in the Ka ≤ 3 rotational ladders to be calculated to within 0.1 km s-1 in radial velocity up to 400 GHz. Conclusive identification of the two astronomical lines of HDCCC was provided by the VLSR, which is the same as for the normal isotopic species (H2CCC) in the three narrow line sources. In these sources, deuterium fractionation in singly substituted H2CCC (HDCCC/H2CCC ~4-19%) is comparable to that in c-C3H2 (c-C3H2/c-C3HD ~5-17%) and similarly in doubly deuterated c-C3H2 (c-C3D2/c-C3HD ~3-17%), implying that the efficiency of the deuteration processes in the H2CCC and c-C3H2 isomers are comparable in dark clouds. Based on observations carried out with the IRAM 30 m Telescope. IRAM is supported by INSU/CNRS (France), MPG (Germany) and IGN (Spain).

  5. 反复输血的受血者不完全抗体和直接抗人球蛋白试验阳性率的研究%The positive rate of irregular antibodies and direct antiglobulin in the blood recipient

    Institute of Scientific and Technical Information of China (English)

    沈柏涛; 谢一唯; 陈秉宇

    2012-01-01

    Objective:To detect and analyze the positive rate of irregular antibody and direct antiglobulin in the blood recipient who have been transfused time after time. Then to distinguish the types of the direct antiglobulin test. Methods; 1291 samples were detected with microcolumn gel coombs test for direct antibody and irregular antibody, and the types of the direct antibodies were distinguished with test tube method. Results; The positive rate of irregular antibody test was 2.09% (27/1291) .among the 27 positive samples, including 12 anti — E samples, 3 autoanti-body samples, 2 anti - D samples, 2 anti - Ec samples, 2 anti - c samples, 1 anti — C sample, 1 anti - e sample, 1 anti - M sample, 1 anti - E and anti - JK" sample, 1 anti - c and autoantibody sample and 1 unkown antibody sample. The positive rate of DAT was 16.7% (216/1291). In the 216 positive samples, there were 46. 76% (101/ 216) , 18.06% (39/216) and 26. 85% (58/216) sensitized by IgG +C3d, IgG and C3d respectively, and other 8. 33% ( 18/216) was not observed. Only 3 samples were both positive for irregular antibodies and direct antibodies and they all had AIHA. Conclusion: The blood recipient who have been transfused time after time all had high positive rate of irregular antibodies and direct antibodies. It could effectively reduce or avoid hemolytic transfusion reaction by conventional antibody screening test among the blood recipient, which was propitious for early diagnosis and treatment of certain disease.%目的:检测和分析反复输血的受血者的不完全抗体和直接抗人球蛋白试验(DAT)的阳性率及DAT分型.方法:采用微柱凝胶抗人球蛋白卡(抗IgG +C3d)检测不完全抗体和DAT,用试管法进行DAT分型.结果:1291例反复输血的受血者不完全抗体的阳性率为2.09%(27/1291),对27例不完全抗体阳性的样本进行抗体鉴定,其中抗E 12例、自身抗体3例、抗D2例、抗Ec2例、抗c2例、抗C1例、抗e1例、抗M1

  6. Activation of mitogen activated protein kinases via complement receptor type 2

    Institute of Scientific and Technical Information of China (English)

    LUO Min-hua 罗敏华; CHEN Ming-liang 陈明亮; Heribert Stoiber; Manfred P Dierich

    2004-01-01

    Background Complement receptor type 2 (CR2) is the receptor for C3d and C3dg and for Epstein-Barr virus. The aim of our study was to explore whether CR2 can independently mediate the activation of mitogen-activated protein kinases (MAPKs, including ERK, JNK, and p38MAPK), and to highlight the molecular mechanism of CD4+ cell deletion in AIDS.Results FACS results showed that the positive rates of HOS-CR2 and HOS-CD4CR2 cells were greater than 96%, and Western blot showed that the CR2 expression levels on HOS-CR2 and HOS-CD4CR2 cells were high. Activation and blocking tests of MAPKs (ERK, JNK, and p38MAPK) were carried out in HOS-CR2, HOS-CD4, and HOS-CD4CR2 cells. The activation of MAPKs in HOS-CR2 cells stimulated with PMA (100 ng/ml) and NHS (10%) was identical. The activation of MAPKs increased at 5 minutes, reached a peak at 10 minutes, and decreased to baseline within 30 minutes, all in a time-dependent manner; the activation of MAPKs was blocked by anti-CR2 McAb, PD98059 (inhibitor of ERK), and Wortmanin (inhibitor of PI-3K), respectively. In HOS-CD4 cells, MAPKs were activated by HIV-gp160. In HOS-CD4CR2 cells, MAPK activation was induced by HIV-gp160, 10% NHS, and HIV-gp160+10%NHS; phosphorylation of p38MAPK was dramatically induced by HIV-gp160+NHS, and lasted for 1 hour. The cell proliferation results showed that HIV-gp160 inhibited the proliferation of HOS-CD4 and HOS-CD4CR2 cells (P<0.01) and that NHS enhanced the effect of HIV-gp160 (P<0.01).Conclusions The activation of MAPKs is independently mediated by CR2 and that anti-CR2 McAb, PD98059, and Wortmanin block the activation of MAPKs, respectively. The results of the signal transduction and cell proliferation assays of HOS-CD4CR2 cells show that CR2 plays a role in the pathogenesis of HIV infection, especially in the inhibition of CD4+ cell proliferation.

  7. IMMUNOHISTOCHEMISTRY VERSUS IMMUNOFLUORESENCE IN THE DIAGNOSIS OF AUTOIMMUNE BLISTERING DISEASES

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2013-11-01

    Full Text Available Introduction: In patients with autoimmune skin blistering diseases (ABDs, the diagnostic gold standard has classically been direct and indirect immunofluorescence (DIF and IIF, despite inherent technical problems of autofluorescence. Aim: We sought to overcome autofluorescence issues and compare the reliability of immunofluorescence versus immunohistochemistry (IHC staining in the diagnoses of these diseases. Methods: We tested via IHC for anti-human IgG, IgM, IgA, IgD, IgE, Kappa light chains, Lambda light chains, Complement/C3c, Complement/C1q, Complement/C3d, albumin and fibrinogen in 30 patients affected by a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF, and 30 control biopsies from the endemic area. We also tested archival biopsies from patients with ABDs whose diagnoses were made clinically, histopathologically and by DIF/IIF studies from 2 independent dermatopathology laboratories in the USA. Specifically, we tested 34 patients with bullous pemphigoid (BP, 18 with pemphigus vulgaris (PV, 8 with pemphigus foliaceus (PF, 14 with dermatitis herpetiformis (DH and 30 control skin samples from plastic esthetic surgery reduction surgeries. Results: The diagnostic correlation between IHC and DIF-IIF was almost 98% in most cases. IHC revealed evidence of autofluorescence around dermal blood vessels, dermal eccrine glands and neurovascular packages feeding skin appendices in ABDs; this autofluorescence may represent a non-specific immune response. Strong patterns of positivity were seen also in endothelial-mesenchymal cell junction-like structures, as well as between dermal fibrohistiocytic cells. In PV, we noted strong reactivity to neurovascular packages supplying sebaceous glands, as well as apocrine glands with edematous changes. Conclusions: We suggest that IHC is as reliable as DIF or IIF for the diagnosis of ABDs; our findings further suggest that what has previously been considered DIF/IIF autofluorescence

  8. Developing and implementing a high precision setup system

    Science.gov (United States)

    Peng, Lee-Cheng

    The demand for high-precision radiotherapy (HPRT) was first implemented in stereotactic radiosurgery using a rigid, invasive stereotactic head frame. Fractionated stereotactic radiotherapy (SRT) with a frameless device was developed along a growing interest in sophisticated treatment with a tight margin and high-dose gradient. This dissertation establishes the complete management for HPRT in the process of frameless SRT, including image-guided localization, immobilization, and dose evaluation. The most ideal and precise positioning system can allow for ease of relocation, real-time patient movement assessment, high accuracy, and no additional dose in daily use. A new image-guided stereotactic positioning system (IGSPS), the Align RT3C 3D surface camera system (ART, VisionRT), which combines 3D surface images and uses a real-time tracking technique, was developed to ensure accurate positioning at the first place. The uncertainties of current optical tracking system, which causes patient discomfort due to additional bite plates using the dental impression technique and external markers, are found. The accuracy and feasibility of ART is validated by comparisons with the optical tracking and cone-beam computed tomography (CBCT) systems. Additionally, an effective daily quality assurance (QA) program for the linear accelerator and multiple IGSPSs is the most important factor to ensure system performance in daily use. Currently, systematic errors from the phantom variety and long measurement time caused by switching phantoms were discovered. We investigated the use of a commercially available daily QA device to improve the efficiency and thoroughness. Reasonable action level has been established by considering dosimetric relevance and clinic flow. As for intricate treatments, the effect of dose deviation caused by setup errors remains uncertain on tumor coverage and toxicity on OARs. The lack of adequate dosimetric simulations based on the true treatment coordinates from

  9. 植物生长调节剂对药用植物三分三种子萌发的影响%Influence of Plant Growth Regulators on Seeds Germination of Medicinal Plant Anisodus acutangulus

    Institute of Scientific and Technical Information of China (English)

    陈林; 赵昱; 李海峰

    2013-01-01

    以药用植物三分三(Anisodus acutangulus C.Y.Wu et C.Chen ex C.Chen et C.L Chen)成熟种子为材料,采用L9(34)正交试验研究赤霉素(GA3)、吲哚乙酸(IAA)、6-苄基腺嘌呤(6-BA)及浸种时间对三分三种子萌发的影响.结果表明,三分三种子萌发的最佳处理是A2B3C1D2,即赤霉素200 rag/L+ 6-苄基腺嘌呤20 mg/L+吲哚乙酸0mg/L+浸种时间24 h,该处理的种子发芽率高达97.8%以上,并且种子开始发芽时间、发芽持续时间较短,种子发芽势、发芽指数最高,是比较理想的种子萌发处理方法.对发芽率进行极差分析以及验证试验的结果显示,影响三分三种子发芽率的最佳处理是A 3B2C3D1,即赤霉素800 mg/L+ 6-苄基腺嘌呤10 mg/L+吲哚乙酸10 mg/L+浸种时间12h;4种因素中以浸种时间对三分三种子发芽率的影响最大,其次是6-苄基腺嘌呤、吲哚乙酸,影响最小的是赤霉素,说明浸种时间过长反而对发芽不利.

  10. Accuracy and Precision in the Detection of Articular Cartilage Lesions Using Magnetic Resonance Imaging at 1.5 Tesla in an In Vitro Study with Orthopedic and Histopathologic Correlation

    International Nuclear Information System (INIS)

    Background: Magnetic resonance (MR) sequences for cartilage visualization have been the target of numerous studies, and the optimal sequence for cartilage imaging remains a matter of debate in the literature. Purpose: To compare MR findings with different MR sequences for the detection of cartilage lesions in fresh deep-frozen human cadaveric patellae in an in vitro setting. Material and Methods: Ten cadaveric patellae were imaged on a 1.5T MR scanner with a 2 x 2 channel carotid sandwich coil and a conventional knee coil, and compared with orthopedic findings and gold-standard histopathology. MR sequences were: a) fat-saturated (FS) proton density-weighted (PDw) turbo spin-echo (TSE) sequence (TR/TE 4000/39 ms); b) T2-weighted (T2w) double-echo steady-state (DESS) 3D water-excitation (we) sequence (TR/TE 17/4.7 ms); c) 3D-PDw-SPACE (sampling perfection with application-optimized contrasts using different flip-angle evolutions)-we sequence (TR/TE 1800/19 ms). Accuracy, Kendall's tau-b correlation, and weighted kappa coefficients were calculated. Results: Accuracy for cartilage lesion detection with the FS PDw-TSE sequence and the carotid coil was 78.3%, and with the knee coil 73.9%. For the T2wDESS-3D-we sequence, the corresponding values were 69.5% and 65.2%, and for the 3D-PDw-SPACE-we sequence 65.2% and 60.8%, respectively. Kendall's tau-b correlation ranged between 0.508 for the 3D-PDw-SPACE-we sequence (knee coil) and 0.720 for the FS PDw-TSE sequence (carotid and knee coil). Weighted kappa coefficient was lowest for the 3D-PDw-SPACE-we sequence (knee coil) at 0.607, and highest for the carotid coil and FS PDw-TSE sequence at 0.779. Conclusion: The evaluated FS PDw-TSE sequences are superior in comparison to the T2wDESS-3D-we and 3D-PDw-SPACE-we sequences in the in vitro setting for the detection of cartilage lesions, and are comparable to results reported in the literature

  11. Solución adyuvante CM-95 tratada magnéticamente en comparación con el adyuvante de Freund para la obtención del suero de Coombs en conejo

    Directory of Open Access Journals (Sweden)

    Clara Martínez

    2009-12-01

    Full Text Available En este trabajo se evaluó la aplicación de la solución CM-95 tratada magnéticamente como adyuvante inmunológico, en comparación con el adyuvante de Freund, para la obtención del suero de Coombs en conejos, de gran demanda en bancos de sangre y hospitales, para el diagnóstico clínico de conflictos Rh y la enfermedad hemolítica del recién nacido, entre otras. Conejos Nueva Zelanda Blancos se inocularon por la vía subcutánea con suero humano obtenido de 30 donantes O+, unido con la solución CM-95 tratada magnéticamente como adyuvante inmunológico. Se empleó un esquema de inmunización de 40 días, donde se evaluó la dinámica en el título de anticuerpos anti IgG humano por la técnica de hemoaglutinación en tubos. Al antisuero se le determinó la calidad inmunológica por el título de heteroaglutininas de los grupos sanguíneos A, B y O, de anticuerpos anticomplemento C3b, C3d y C4b y anti IgG, antes y después de su purificación. El suero de Coombs con la solución adyuvante CM-95 tratada magnéticamente mostró valores similares a los obtenidos con el adyuvante de Freund. En el mismo se cumplió con los requisitos establecidos por el Centro Estatal para el Control de la Calidad de los Medicamentos, según las normativas de la FDA para este diagnosticador. Estos resultados abren nuevas perspectivas para el uso de la solución adyuvante en la obtención del suero de Coombs.

  12. On thermonuclear processes in cavitation bubbles

    Science.gov (United States)

    Nigmatulin, R. I.; Lahey, R. T., Jr.; Taleyarkhan, R. P.; West, C. D.; Block, R. C.

    2014-09-01

    The theoretical and experimental foundations of so-called bubble nuclear fusion are reviewed. In the nuclear fusion process, a spherical cavitation cluster ˜ 10-2 m in diameter is produced of spherical bubbles at the center of a cylindrical chamber filled with deuterated acetone using a focused acoustic field having a resonant frequency of about 20 kHz. The acoustically-forced bubbles effectuate volume oscillations with sharp collapses during the compression stage. At the final stages of collapse, the bubble cluster emits 2.5 MeV D-D fusion neutron pulses at a rate of ˜ 2000 per second. The neutron yield is ˜ 10^5 s -1. In parallel, tritium nuclei are produced at the same yield. It is shown numerically that, for bubbles having sufficient molecular mass, spherical shock waves develop in the center of the cluster and that these spherical shock waves (microshocks) produce converging shocks within the interior bubbles, which focus energy on the centers of the bubbles. When these shock waves reflect from the centers of the bubbles, extreme conditions of temperature ( ˜ 10^8 K) and density ( ˜ 10^4 kg m -3) arise in a (nano)spherical region ( ˜ 10-7 m in size) that last for ˜ 10-12 s, during which time about ten D-D fusion neutrons and tritium nuclei are produced in the region. A paradoxical result in our experiments is that it is bubble cluster (not streamer) cavitation and the sufficiently high molecular mass of (and hence the low sound speed in) D-acetone ( C3D6O) vapor (as compared, for example, to deuterated water D2O) which are necessary conditions for the formation of convergent spherical microshock waves in central cluster bubbles. It is these waves that allow the energy to be sufficiently focused in the nanospherical regions near the bubble centers for fusion events to occur. The criticism to which the concept of 'bubble fusion' has been subjected in the literature, in particular, most recently in Uspekhi Fizicheskikh Nauk (Physics - Uspekhi) journal, is

  13. Synthesis of O'-SiAlON-BN Composite by Reaction Sintering

    Institute of Scientific and Technical Information of China (English)

    ZHEN Qiang; YAN Kai; ZHANG Dahai; LI Wenchao

    2006-01-01

    By using micron α-Si3N4, SiO2, Al2O3 and h-BN as starting materials, O' -SiAlON-BN ( Si2-ZAlzO1+zN2-z, z = 0.3) composite was synthesized by reaction sintering. According to theoretical proportion ratio:n(SiO2)/n(α-Si3N4) = 1, the effects of two sintering aid comtosites, Y2O3+B2O3 and Y2O3+TiO2 at 1700℃ for 2h, were studied. The results indicate that Y2O3+TiO2 as sintering aid can accelerate reaction sintering of O'-SiAlON-BN more effectively than Y2O3+B2O3, and the relative density of the composites declined with the increase of BN addition (10%, 20% and30% respectively); XRD analysis found that excessive β-Si3N4 existed in the O' -SiAlON-BN composite. Therefore, in order to get more pure O' -SiAlON and BN phases in the composites ore SiO2 is needed. When Y2O3+TiO2 was used as sintering aid and addition of BN was 10%, the result of cross experiment on condition of A n(SiO2)/n(α-Si3N4) was 1.05, 1.1 and1.2; B addition of sintering aid was 2%, 4% and 6%; C firing temperature was 1600℃, 1650℃ and 1700℃ ;D-soaking time was 1h, 2h and 3h, shows that the sintering properties were influenced by factors of firing temperature, soaking time, addition of sintering aid and n(SiO2)/n(α-Si3N4) in order of importance. In addition, the technical parameter A3B3C3D3 can achieve the highest relative density. Besides, using Pattern Recognition method, the optimized parameter range to form pure O' -SiAlON and BN without β-Si3N4 remained was determined as Y > 1024X2 - 230.400X+11.088 ( X =0.9999A-0.0006C-0.0163D, Y =0.0163A +0.0009B -0.0014C+0.9999D).

  14. High-Density Integration and Single-Chip Multi-Core Systems and Research Progresses%高密度集成与单芯片多核系统及其研究进展

    Institute of Scientific and Technical Information of China (English)

    李东生; 高明伦

    2012-01-01

    在体积、重量和功耗有严格约束的情况下,系统小型化遇到多种技术挑战,为了满足高密度计算和小型化的要求,高密度系统集成和单芯片多核处理器至关重要.讨论了高密度集成与单芯片多核处理器技术及其研究进展,其中包括单芯片多核处理器( CMP)、片上网络( NoC)、3D集成电路、高密度封装.提出了CMP的两个发展特征,即小核大数量和层次型簇结构.指出高密度集成设计与高密度封装设计逐渐融合,并为单芯片多核系统的物理实现提供了技术保证,为最终实现高密度计算和小型化系统提供了硬件解决方案.%When size, weight and power are critical constraints, the system miniaturization encounters a variety of technical challenges. To meet the high-density computing and the requirements of miniaturization, high density system integration and single-chip multi-core processor technology are important technologies. The high-density integration and single-chip multi-core processor technology and research progresses are discussed, including single-chip multi-core processors (CMP) , network on chip (NoC) , 3D integrated circuits and high-density packaging. The two characteristics of CMP are presented, I. E. The large number of small cores and hierarchical cluster structures. High-density integrated design and high-density packaging design gradually integrate to serve the physical realization of single-chip multi-core system. And it provides a hardware solution for miniaturization of high-density computing systems.

  15. Site-Specific Rate Constant Measurements for Primary and Secondary H- and D-Abstraction by OH Radicals: Propane and n -Butane

    KAUST Repository

    Badra, Jihad

    2014-07-03

    Site-specific rate constants for hydrogen (H) and deuterium (D) abstraction by hydroxyl (OH) radicals were determined experimentally by monitoring the reaction of OH with two normal and six deuterated alkanes. The studied alkanes include propane (C3H8), propane 2,2 D2 (CH 3CD2CH3), propane 1,1,1-3,3,3 D6 (CD 3CH2CD3), propane D8 (C3D 8), n-butane (n-C4H10), butane 2,2-3,3 D4 (CH3CD2CD2CH3), butane 1,1,1-4,4,4 D6 (CD3CH2CH2CD3), and butane D10 (C4D10). Rate constant measurements were carried out over 840-1470 K and 1.2-2.1 atm using a shock tube and OH laser absorption. Previous low-temperature data were combined with the current high-temperature measurements to generate three-parameter fits which were then used to determine the site-specific rate constants. Two primary (P1,H and P 1,D) and four secondary (S00,H, S00,D, S 01,H, and S01,D) H- and D-abstraction rate constants, in which the subscripts refer to the number of C atoms connected to the next-nearest-neighbor C atom, are obtained. The modified Arrhenius expressions for the six site-specific abstractions by OH radicals are P1,H = 1.90 × 10-18T2.00 exp(-340.87 K/T) cm 3molecule-1s-1 (210-1294 K); P1,D= 2.72 × 10-17 T1.60 exp(-895.57 K/T) cm 3molecule-1s-1 (295-1317 K); S00,H = 4.40 × 10-18 T1.93 exp(121.50 K/T) cm 3molecule-1s-1 (210-1294 K); S00,D = 1.45 × 10-20 T2.69 exp(282.36 K/T) cm 3molecule-1s-1 (295-1341 K); S01,H = 4.65 × 10-17 T1.60 exp(-236.98 K/T) cm 3molecule-1s-1 (235-1407 K); S01,D = 1.26 × 10-18 T2.07 exp(-77.00 K/T) cm 3molecule-1s-1 (294-1412 K). © 2014 American Chemical Society.

  16. A shock tube study of the branching ratios of propene + OH reaction

    KAUST Repository

    Badra, Jihad

    2014-12-01

    Absolute rate coefficients for the reaction of the OH radical with propene (C3H6) and five deuterated isotopes, propene-1-D1 (CDHCHCH3), propene-1,1-D2 (CD2CHCH3), propene-1,1,2-D3 (CD2CDCH3), propene-3,3,3-D3 (CH2CHCD3), and propene-D6 (C3D6), were measured behind reflected shock waves over the temperature range of 818-1460 K and pressures near 1 atm. The reaction progress was followed by monitoring the OH radical near 306.7 nm using UV laser absorption. Kinetic isotope effects in the measured rate coefficients are discussed and rationalized for the site-specific H-abstraction by the OH radical. The first experimental measurements for the branching ratio of the title reaction are reported and compared with transition state theory calculations. The allylic H-atom abstraction of propene by OH radicals was found to be the most dominant reaction pathway followed by propen-1-yl and propen-2-yl channels over the entire temperature range of this study. The derived Arrhenius expressions for various site-specific rate coefficients over 818-1442 K are (the subscript in the rate coefficient identifies the position of H or D atom according to the IUPAC nomenclature of alkenes):k3,H = 2.32 × 10-11 exp(-2341 K/T) cm3 molecule-1 s-1k3,D = 1.96 × 10-11 exp(-2420 K/T) cm3 molecule-1 s-1k1,H = 1.39 × 10-11 exp(-2270 K/T) cm3 molecule-1 s-1k1,D = 1.95 × 10-11 exp(-2868 K/T) cm3 molecule-1 s-1k2,H = 7.2 × 10-12 exp(-2282 K/T) cm3 molecule-1 s-1k2,D = 7.69 × 10-12 exp(-2575 K/T) cm3 molecule-1 s-1 This journal is

  17. The regulatory SCR-1/5 and cell surface-binding SCR-16/20 fragments of factor H reveal partially folded-back solution structures and different self-associative properties.

    Science.gov (United States)

    Okemefuna, Azubuike I; Gilbert, Hannah E; Griggs, Kim M; Ormsby, Rebecca J; Gordon, David L; Perkins, Stephen J

    2008-01-01

    Factor H (FH) is a plasma glycoprotein that plays a central role in regulation of the alternative pathway of complement. It is composed of 20 short complement regulator (SCR) domains. The SCR-1/5 fragment is required for decay acceleration and cofactor activity, while the SCR-16/20 fragment possesses binding sites for complement C3d and heparin. X-ray scattering and analytical ultracentrifugation showed that SCR-1/5 was monomeric, while SCR-16/20 formed dimers. The Guinier radius of gyration R(G) of 4.3 nm for SCR-1/5 and those of 4.7 nm and about 7.8 nm for monomeric and dimeric SCR-16/20, respectively, showed that their structures are partially folded back and bent. The distance distribution function P(r) showed that SCR-1/5 has a maximum dimension of 15 nm while monomeric and dimeric SCR-16/20 are 17 nm and about 27 nm long, respectively. The sedimentation coefficient of 2.4 S for SCR-1/5 showed no concentration-dependence, while that for SCR-16/20 was 2.8 S for the monomer and 3.9 S for the dimer. Sedimentation equilibrium data showed that SCR-1/5 is monomeric while SCR-16/20 exhibited a weak monomer-dimer equilibrium with a dissociation constant of 16 microM. The constrained scattering and sedimentation modelling of SCR-1/5 and SCR-16/20 showed that partially folded-back and bent flexible SCR arrangements fitted both data sets better than extended linear arrangements, and that the dimer was best modelled in the SCR-16/20 model by an end-to-end association of two SCR-20 domains. The SCR-1/5 and SCR-16/20 models were conformationally similar to the previously determined partially folded-back structure for intact wild-type FH, hence suggesting a partial explanation of the intact FH structure. Comparison of the SCR-16/20 model with the crystal structure of C3b clarified reasons for the distribution of mutations leading to atypical haemolytic uraemic syndrome.

  18. Briquett Process of Vanadium and Titanium Iron Concentrate Pellets Containing Carbon%钒钛铁精矿内配碳球团压团工艺研究

    Institute of Scientific and Technical Information of China (English)

    刘松利; 白晨光; 胡途

    2011-01-01

    Pellets containing carbon performance such as falling number, compressive strength and so on were extremely important to get higher metallization rate for producing sponge iron by direct reduction methods. First, each factor of benchmark parameters was determined preliminary, a series of single factor experiments were investigated by changing the parameters value. Then, according to the principle of orthogonal test design, the four factors and three levels test conditions were designed. Briquette process parameters of vanadium and titanium iron concentrate pellets containing carbon were studied using 769YP-60E type manual briquette machine. Finally, test dates were analyzed by extreme difference analysis and variance analysis. Influence factors of pelletizing properties were tested. Research results showed that process conditions on higher falling number of raw pellets which were determined by comprehensive comparison of experimental results and extreme difference analysis respectively were A2B2C3D2, namely mine and coal size ratio was 200= 60, moisture was 8% , binder was 0.3% , and pressure was 10 MPa. Variance analysis was used to distinguish different results which were induced by factors level changes and error fluctuation. The main affecting factors of pellets performance or briquette process parameters respectively were B2A2D2C3, namely pellets moisture, mine and coal size ratio, pressure and binder concentration. Raw pellets must be processed by drying. When the drying temperature was 105 ℃, the drying time was controlled in 2 h. The compressive strength of the pellets was 98 N/a, high temperature burst performance of the pellets was less than 20% , which could meet the requirement of direct reduction process by rotary hearth furnace.%内配碳球团性能(落下次数、抗压强度等),对于直接还原生产海绵铁时获得较高金属化率极为重要.首先初步确定每个因素的基准参数,通过改变其参数值进行一系列单

  19. Development and Calibration of New 3-D Vector VSP Imaging Technology: Vinton Salt Dome, LA

    Energy Technology Data Exchange (ETDEWEB)

    Kurt J. Marfurt; Hua-Wei Zhou; E. Charlotte Sullivan

    2004-09-01

    Vinton salt dome is located in Southwestern Louisiana, in Calcasieu Parish. Tectonically, the piercement dome is within the salt dome minibasin province. The field has been in production since 1901, with most of the production coming from Miocene and Oligocene sands. The goal of our project was to develop and calibrate new processing and interpretation technology to fully exploit the information available from a simultaneous 3-D surface seismic survey and 3-C, 3-D vertical seismic profile (VSP) survey over the dome. More specifically the goal was to better image salt dome flanks and small, reservoir-compartmentalizing faults. This new technology has application to mature salt-related fields across the Gulf Coast. The primary focus of our effort was to develop, apply, and assess the limitations of new 3-C, 3-D wavefield separation and imaging technology that could be used to image aliased, limited-aperture, vector VSP data. Through 2-D and 3-D full elastic modeling, we verified that salt flank reflections exist in the horizontally-traveling portion of the wavefield rather than up- and down-going portions of the wavefield, thereby explaining why many commercial VSP processing flow failed. Since the P-wave reflections from the salt flank are measured primarily on the horizontal components while P-wave reflections from deeper sedimentary horizons are measured primarily on the vertical component, a true vector VSP analysis was needed. We developed an antialiased discrete Radon transform filter to accurately model P- and S-wave data components measured by the vector VSP. On-the-fly polarization filtering embedded in our Kirchhoff imaging algorithm was effective in separating PP from PS wave images. By the novel application of semblance-weighted filters, we were able to suppress many of the migration artifacts associated with low fold, sparse VSP acquisition geometries. To provide a better velocity/depth model, we applied 3-D prestack depth migration to the surface data

  20. 计算机导航辅助骨样骨瘤的外科治疗%Computer navigation-guided excision of osteoid osteomas

    Institute of Scientific and Technical Information of China (English)

    王涛; 张清; 牛晓辉; 鱼锋; 李远; 赵海涛; 刘巍峰; 马珂; 杨发军

    2011-01-01

    目的 探讨计算机导航技术在骨样骨瘤外科治疗中的意义.方法 回顾性分析2008年1月至2009年12月应用计算机导航辅助切除骨样骨瘤手术26例患者的临床资料,其中男性23例,女性3例,平均年龄18岁(7~35岁).26例患者肿瘤位于股骨干9例、股骨粗隆部4例、股骨颈2例、胫骨干5例、胫骨近端干骺端1例、髋臼2例、耻骨1例、脊柱附件1例、桡骨干1例.术前均经局部X线及CT扫描明确诊断.其中4例采用CT数据导航,22例采用Iso-C 3D C型臂术中实时导航.术中导航指引定位,精确切除瘤巢.结果 全部病例均完成导航手术,其中行开窗刮除12例、整块切除14例;植骨21例、未植骨5例.26例患者均经术中肉眼判定、术中导航指引器确认、术后X线和(或)CT扫描确认瘤巢去除充分.全部病例均经组织病理学确诊为骨样骨瘤,术后疼痛即刻缓解.全部病例均获随访,平均随访20.6个月(12~35个月),未见肿瘤复发和疼痛复发.结论 将计算机导航技术应用于骨样骨瘤的外科治疗,不仅使术中瘤巢定位更精确,而且对于复杂部位瘤巢的切除可以达到骨结构微创治疗的目的.对于骨干部位的骨样骨瘤,Iso-C 3D C型臂术中实时导航较CT数据导航更有帮助.%Objective To report the experience for the precision osteoid osteoma resection using computer navigation system. Methods Between January 2008 and December 2009, 26 surgical resections were performed for 26 patients who had osteoid osteoma with computer navigation system. There were 23 males and 3 females with an average age of 18 years (7 to 35). Tumors were located at femoral shaft 9,femoral trochanter 4, femoral neck 2, tibial shaft 5, metaphysic of proximal tibia 1, acetabulum 2, pubis 1,vertebral appendix 1 and radial shaft 1. Pre-operative X-ray and CT of each patient was performed to confirm the diagnosis. It was carried out intraoperatively the process of CT-based navigation in 4

  1. Intern Abstract for Spring 2016

    Science.gov (United States)

    Gibson, William

    2016-01-01

    The Human Interface Branch - EV3 - is evaluating Organic lighting-emitting diodes (OLEDs) as an upgrade for current displays on future spacecraft. OLEDs have many advantages over current displays. Conventional displays require constant backlighting which draws a lot of power, but with OLEDs they generate light themselves. OLEDs are lighter, and weight is always a concern with space launches. OLEDs also grant greater viewing angles. OLEDs have been in the commercial market for almost ten years now. What is not known is how they will perform in a space-like environment; specifically deep space far away from the Earth's magnetosphere. In this environment, the OLEDs can be expected to experience vacuum and galactic radiation. The intern's responsibility has been to prepare the OLED for a battery of tests. Unfortunately, it will not be ready for testing at the end of the internship. That being said much progress has been made: a) Developed procedures to safely disassemble the tablet. b) Inventoried and identified critical electronic components. c) 3D printed a testing apparatus. d) Wrote software in Python that will test the OLED screen while being radiated. e) Built circuits to restart the tablet and the test pattern, and ensure it doesn't fall asleep during radiation testing. f) Built enclosure that will house all of the electronics Also, the intern has been working on a way to take messages from a simulated Caution and Warnings system, process said messages into packets, send audio packets to a multicast address that audio boxes are listening to, and output spoken audio. Currently, Cautions and Warnings use a tone to alert crew members of a situation, and then crew members have to read through their checklists to determine what the tone means. In urgent situations, EV3 wants to deliver concise and specific alerts to the crew to facilitate any mitigation efforts on their part. Significant progress was made on this project: a) Open channel with the simulated Caution

  2. Seismic Technology Adapted to Analyzing and Developing Geothermal Systems Below Surface-Exposed High-Velocity Rocks Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Hardage, Bob A. [Univ. of Texas, Austin, TX (United States). Bureau of Economic Geology; DeAngelo, Michael V. [Univ. of Texas, Austin, TX (United States). Bureau of Economic Geology; Ermolaeva, Elena [Univ. of Texas, Austin, TX (United States). Bureau of Economic Geology; Hardage, Bob A. [Univ. of Texas, Austin, TX (United States). Bureau of Economic Geology; Remington, Randy [Univ. of Texas, Austin, TX (United States). Bureau of Economic Geology; Sava, Diana [Univ. of Texas, Austin, TX (United States). Bureau of Economic Geology; Wagner, Donald [Univ. of Texas, Austin, TX (United States). Bureau of Economic Geology; Wei, Shuijion [Univ. of Texas, Austin, TX (United States). Bureau of Economic Geology

    2013-02-01

    applications by inserting into this report a small part of the interpretation we have done with 3C3D data across Wister geothermal field in the Imperial Valley of California. This interpretation shows that P-SV data reveal faults (and by inference, also fractures) that cannot be easily, or confidently, seen with P-P data, and that the combination of P-P and P-SV data allows VP/VS velocity ratios to be estimated across a targeted reservoir interval to show where an interval has more sandstone (the preferred reservoir facies). The conclusion reached from this investigation is that S-wave seismic technology can be invaluable to geothermal operators. Thus we developed a strong interest in understanding the direct-S modes produced by vertical-force sources, particularly vertical vibrators, because if it can be demonstrated that direct-S modes produced by vertical-force sources can be used as effectively as the direct-S modes produced by horizontal-force sources, geothermal operators can acquire direct-S data across many more prospect areas than can be done with horizontal-force sources, which presently are limited to horizontal vibrators. We include some of our preliminary work in evaluating direct-S modes produced by vertical-force sources.

  3. 饥饿和再投喂对中间球海胆代谢和生长的影响%Effects of starvation and refeeding on metabolism and growth in sea urchin, Strongylocentrotus intermedius

    Institute of Scientific and Technical Information of China (English)

    秦艳杰; 李霞; 吴立新; 周一兵

    2011-01-01

    The sea urchin (Strongylocentrotus intermedins) with body weight of (5. 72±0. 23) g was starved for 0 (control group, C) , 3 d (S3) , 6 d (S6) , 9 d (S9) and 12 d (S12) , and then re-fed until the 30th d to evaluate the effects of starvation on growth and metabolism in the sea urchin. The wet weight of whole body and gonad, special growth rate of body and gonad, the oxygen consumption rate, ammonia excretion rate and the food conversion efficiency were measured and calculated every five days in control group, on the day at the end of starvation, and 2,4,8 and 12 days after re-fed in four starved groups. Results showed that there were no significant differences in body wet weight between S3, S6 and C groups at the end of the experiment, but significantly lower in S9 and S12 than those in the control. There was significantly lower in gonad wet weight in S6, S9 and S12 compared to C and S3 at the end. The sea urchin in S6, S9 and S12 showed a peak in special growth rate in body and gonad after re-fed and lasted 3-5 days. The oxygen consumption rate and ammonia excretion rate were found to decrease for 4-8 days in S6, S9 and S12 at the beginning of re-fed. The food conversion efficiencies were increased in varying degrees after re-fed in the four experimental groups. It is indicated that the food deprivation for 6 d, 9 d and 12 d leads to part compensatory growth in the sea urchin, which are contributed in the significant decrease in metabolic rate and the increase in the food conversion efficiency during the initial stage of refeeding.%将体质量为(5.72±0.23)g的中间球海胆Strongylocentrotus intermedius分别饥饿0、3、6、9、12 d(分别记为C、S3、S6、S9、S12)后再饱食投喂至30 d,研究了饥饿与再投喂过程中海胆的代谢率、生长率、摄食率、食物转化率的变化.结果表明:在饥饿和再投喂过程中,S3组各指标与对照组无明显差异;S6、S9、S12组在恢复投喂过程中的一段时间内代谢率均维

  4. 番茄红素抗氧化应激效应对大鼠脊髓损伤后运动功能恢复的影响①%Anti-oxidative Stress Effect of Lycopene on Motor Function after Spinal Cord Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    李晓; 卓睿; 李亚光; 罗晨禹; 杨拯; 谢少华; 张尧; 杨海燕; 马延仃; 张艺; 胡雯思

    2013-01-01

    .05); the activity of SOD significantly increased in Group C 1 d, 3 d and 7 d, and in Group B 3 d, 7 d after operation (P<0.05); the content of MDA significantly decreased in Group C 3 d, 7 d, and in Group B 1 d, 7 d after operation (P<0.05). Conclusion Lycopene can reduce the level of oxidative stress and promote the motor function in rats after acute SCI.

  5. Analysis of screening results of irregular antibodies before blood transfusion%输血前不规则抗体筛查结果分析

    Institute of Scientific and Technical Information of China (English)

    邹文涛; 何子毅; 李俊杰; 刘仁强; 刘景春

    2008-01-01

    Objective To identify serum or plasma irregular antibodies in patients, analyze their distribution characteristic, so as to prevent hemolytic transfusion reaction.Methods Microcolumn gel immunoassay was applied to screening and identifying irregular antibodies in clinical suspicious matching blood samples from June 2006 to December 2007, and then the types and distribution characteristic of irregular antibodies were analyzed.Results 54 cases were irregular antibody positive, in which 28 cases (51.85%) were homologous antibodies, 26 cases (48.15%) were autologous antibodies, 2 cases were unidentified antibodies. In homologous antibodies,Rh system antibody was predominant (53.57%) (in which anti-E was more than anti-D), followed by MNSs system antibody (19.23%). Anti-M (5, 9.26%) was the most in MNSs system. In autologous antibodies, anti-IgG was the most (53.84%), followed by anti-IgG+anti-C3d (30.77%) and cold autoantibody (15.38%). No hemolytic transfusion reaction occurred in patients with isoantibody after infusion of blood with corresponding antigen negative. The symptom of anaemia was alleviated in patients with autoantibody after quantitative washed red cells infusion.Conclusion Screening of irregular antibodies and infusion of suitable blood are conductive to decrease or avoidance of hemolytic transfusion reaction, and guarantee of blood safety.%目的 输血前对患者血清(浆)进行不规则抗体筛选和鉴定,分析不规则抗体的分布特征,预防溶血性输血反应的发生.方法 用微柱凝胶法对2006年6月到2007年12月间临床送检的疑难配血标本进行不规则抗体筛选和鉴定,分析不规则抗体的类型和分布特征.结果 不规则抗体筛选鉴定阳性54例,其中同种抗体26(51.85%)例,自身抗体26(48.15%)例,抗体特异性未确定2例,同种抗体中以Rh系统最多,占15/28(53.57%),其次为MNSs系统,占5/26(19.23%),Rh系统抗-E明显多于抗-D,与以往文献报道不同;MNSs系统主要是抗-M;

  6. Proliferation of resting B cells is modulated by CR2 and CR1.

    Science.gov (United States)

    Fingeroth, J D; Heath, M E; Ambrosino, D M

    1989-06-15

    Absence of the third component of complement, C3, is associated with impaired ability to synthesize antibody, particularly in the presence of limiting antigen [1-9]. The mature B lymphocyte bearing the surface immunoglobulin receptor transduces signals for proliferation and differentiation upon binding of specific antigen. This mature B cell also bears two related membrane proteins, CR2 (the C3d/Epstein-Barr virus receptor) (CD35) [15], which can mediate the binding of ligands to which appropriate cleavage fragments of C3 have become attached [16]. It has been suggested that these receptors play a direct role(s) in B cell activation [17-25]. In light of previous in vivo observations we decided to assess the function of CR2 and CR1 in relation to B cell activation through the membrane IgM receptor. Highly purified splenic B cells were prepared. No contaminating T cells or macrophages were detected by flow cytometric analysis and no proliferative activity was present upon PHA or ConA stimulation of the purified cells. The B cells were separated into low (activated), medium (preactivated) and high density (resting) fractions by Percoll gradient density centrifugation [26]. The responses of the B cell subpopulations to various concentrations of anti mu (DA4.4 monoclonal antibody) [27] were examined for proliferation at 72 h and for IgM/IgG production at 7 days. Low density B cells were maximally stimulated and no concentration of anti-mu was effective in enhancing their responses. High density B cells proliferated to anti-mu in a concentration dependent manner. When substimulatory concentrations of anti-mu were employed, concomitant crosslinking of CR2 (with either of 2 distinct monoclonal antibodies HB-5 [28] or OKB7 [17]) resulted in a 45% enhancement of B cell proliferation above that observed by crosslinking of SIgM alone. In these studies, total IgM and IgG did not increase in the absence of T cells or T cell factors, indicating that terminal differentiation did

  7. 骨性Ⅲ类错(牙合)下前牙区牙槽骨形态的锥形束CT分析%Preliminary cone-beam computed tomography study of alveolar bone of anterior mandible in adults with skeletal Class Ⅲ malocclusion

    Institute of Scientific and Technical Information of China (English)

    张莉; 王博; 房兵

    2012-01-01

    PURPOSE: To evaluate the thickness of alveolar bone of mandibular anterior teeth in adults with skeletal Class Ⅲ malocclusion by a method of detailed cone-beam computed tomography (CBCT) images. METHODS: The subjects were 45 untreated patients with skeletal Class III malocclusion and 45 untreated patients with skeletal Class I malocclusion. They were divided into 2 groups: skeletal Class III and skeletal Class I patients. Tomography was carried out using KODAK9000C 3D volume scanner before orthodontic treatment. Three-dimensional CBCT software (Kodak dental imaging software 3D module v 2.4, Eastman Kodak Company, French) was used to measure the labial, lingual and total thickness of alveolar bone of mandibular anterior teeth by 6 reference points. The thicknesses of alveolar bone of both groups were measured along an axial plane at mandibular anterior teeth root apex levels from a CBCT image. Differences between the 2 groups were analyzed by using group t test with SPSS16.0 software package. RESULTS: The thickness of the alveolar bone of mandibular anterior teeth was greater in the skeletal Class I than the skeletal Class III subjects. There was significant (P<0.05) difference between the two groups. CONCLUSIONS: The thickness of alveolar bone of mandibular anterior segment was obviously thinner in the skeletal Class III malocclusion than that in Class I. More attention was recommended to be paid in skeletal Glass HI patient. Supported by National Natural Science of China (10972142), Research Fund of Science and Technology Commission of Shanghai Municipality (08411961600) and Program for Innovative Research Team of Shanghai Municipal Education Commission.%目的:应用锥形束CT(cone-beam computed tomography,CBCT)评价骨性Ⅲ类和骨性I类错猞患者下颌切牙区 牙槽骨形态的差异。方法:选取45例恒牙期骨性Ⅲ类错治病例及45例恒牙期骨性I类错骀病例矫治前的CBCT图 像,测量下切牙区

  8. 生物工程学

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    靶向ASGPR的反义核酸与抗HBV药物联合用药的体外抗HBV作用;新城疫病毒F蛋白细胞融合活性位点中保守氨基酸基因突变分析;亲和层析法用于噬菌体抗体库的筛选;减蛋综合征病毒六邻体重组蛋白的表达和初步应用;融合表达牛疱疹病毒1型VP22及猪繁殖与呼吸综合征病毒GP5重组伪狂犬病毒TK-/gE-/VP22 GP5+的构建;猪1型圆环病毒全基因组克隆及其感染性初步鉴定;应用双向启动子RNA干扰技术抑制ICOS表达;人IL-3基因cDNA的克隆及其在造血干细胞的表达;应用RNAi技术沉默STAT3基因对乳腺癌MCF-7细胞的影响;表达结核分枝杆菌融合蛋白的DNA疫苗构建及免疫保护;应用噬菌体;GST Pull-down实验鉴定;色素上皮细胞;CT-1及TTC的GST融合蛋白;SV40TAg真核表达;以病毒样颗粒;大花蕙兰基因;QS系统中LasR;基于DNA的Semliki;小麦耐逆基因;PttGA200x1基因在转化;香蕉果实β-1;盐胁迫下盐;hCGβ-C3d3基因免疫;特异小干扰;牛乳腺核基质;小麦新品种;桃ACO基因反义;pBR322-Red介导的;一种新的分子;基于载体的RNA;黄鳝Nup93基因;重组人BMP-2;盐生杜氏藻;植物维生素;单纯疱疹病毒;Hsp70与汉滩;SSII技术筛选;猪圆环病毒;H5N1亚型禽流感;HaSNPV的9个基因;表达LacZ基因;猪瘟病毒结构;SARS相关冠状;SARS冠状病毒;人LIGHT胞外区;BALB/c小鼠Ⅰ-Ad αβ;重组MAGE-A1/EGFP;癌胚抗原基因;牛IL-18基因;HIV-1整合酶;一种抗菌肽;两种标记方法;重组人胰高血;RAPD分子标记;Red重组技术;毕赤酵母表达;双链RNA激活;黑色素瘤相关抗原;外源性人TIMP-1;人多肽N-乙酰;乙型肝炎病毒;人疱疹病毒;人工合成苯;PCR合成的A型;葎草及豚草;HIV-2 gag rFPV;密码修饰可增;甘蓝MLPK基因;烟草抗TMV基因;快速检测干旱;动员后兔外周;针对单克隆;抗大肠杆菌;影响香根草;人胚胎干细胞;一株新型抗;Tet调控STGC3基因;珍稀濒危植

  9. FEATURES IMMUNOLOGIC INDICATORS OF CHRONIC TONSILLITIS ASSOCIATED WITH EPSTEIN-BARR VIRUS IN ADULTS

    Directory of Open Access Journals (Sweden)

    Kuchma I.U

    2014-10-01

    Full Text Available Chronic tonsillitis are the most common diseases of the upper respiratory tract. One of the causes of tonsillitis, with severe clinical manifestations or erased is the Epstein - Barr virus (EBV. According to the literature, more than 90% of the adult population infected with EBV and are lifelong carriers of the virus. After primary infection replication of the virus in asymptomatic or in the case of a weakened immune system may develop infectious mononucleosis. Primary EBV infection in adolescence and adults is much greater than in children and often causes the formation of chronic forms. The main entrance gate is EBV oropharyngeal epithelium. In epithelial cells undergoing complete EBV replication with lysis of cells and the formation of a large number of virions. EBV infects B lymphocytes through the interaction of the surface gp320 virus with CD21 (receptor for complement component C3d. In EBV-infected B lymphocytes are two possible kinds of replication: lytic and latent process. During replication of EBV lytic expressed approximately 100 proteins are immunogenic but are 4 types of proteins, which have specific antibodies: early antigen - EA; viral capsid antigen - VCA; Epstein-Barr nuclear antigen - EBNA; latent membrane protein - LMP. LMP-1 induced bcl-2 (a blocker of apoptosis in B-cells and promotes proliferation and migration of B-lymphocytes. Thus, EBV infection is characterized by widespread, reactivation of infection from infected parts that most often manifests itself with recurrent infection with symptoms of chronic tonsillitis. Objective: what features of general and local immunological parameters inherent in chronic tonsillitis in the acute stage, caused by reactivation of EBV infection. Materials and methods. The study included 311 patients with chronic tonsillitis subcompensated in the acute stage. Microbiological testing of samples produced from the throat, determined EBV DNA in saliva, EVB-VCA-IgM, EVB-EA-IgG and EVB-NA-IgG in

  10. Computer navigation-guided percutaneous radiofrequency ablation of the osteoid osteomas:13-case report%计算机导航辅助经皮射频消融治疗骨样骨瘤13例报告

    Institute of Scientific and Technical Information of China (English)

    鱼锋; 张清; 赵海涛; 徐立辉; 牛晓辉

    2014-01-01

    目的:探讨计算机导航技术辅助经皮射频消融治疗骨样骨瘤手术方法和临床效果。方法回顾性分析2011年6月至2012年11月,我科应用计算机导航辅助经皮射频消融治疗骨样骨瘤13例的临床资料,其中男12例,女1例,平均16.5(8~36)岁。术前均经局部X线、CT、MRI明确诊断。肿瘤位于股骨干4例、股骨粗隆2例、股骨颈2例、股骨髁2例、胫骨干2例、跟骨1例。13例均采用Iso-C 3D C型臂术中实时导航,计算机软件均使用Stryker公司的脊柱导航软件。术中导航指引定位,骨活检针(9G )精确到达瘤巢,行穿刺活检,保留套筒,将射频针导入瘤巢,90℃消融6 min。术后进行随访,并采用疼痛视觉类比评分法( VAS )和术后X线、CT判断疗效。结果13例均获11.2(4~20)个月的随访。全部病例均完成计算机导航辅助下射频消融手术,11例组织病理学确诊为骨样骨瘤,2例组织学无法诊断,病理确诊率85%。术后疼痛即刻缓解,VAS评分显著降低。术前平均4.7,术后3天1.3,术后3个月为0.1,差异有统计学意义( P<0.05)。全部病例随访未见肿瘤复发和疼痛复发。结论经皮射频消融治疗骨样骨瘤是一种简单、安全、有效的治疗方法。计算机导航技术的应用,使术中瘤巢定位更精确,使手术治疗的微创化成为现实。%Objective To investigate the surgical method and clinical results of computer navigation-guided percutaneous radiofrequency ablation ( RFA ) in the treatment of osteoid osteomas. Methods From June 2011 to November 2012, 13 patients with osteoid osteomas were treated with computer navigation-guided percutaneous RFA, whose clinical data were retrospectively analyzed. There were 12 men and 1 woman with a mean age of 16.5 years old ( range;8-36 years ). Preoperatively all the diagnoses were conifrmed by the local X-ray, CT and MRI examinations. The femoral diaphysis was the most