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Sample records for adhesion blocking antibodies

  1. Bacterial Adhesion & Blocking Bacterial Adhesion

    DEFF Research Database (Denmark)

    Vejborg, Rebecca Munk

    2008-01-01

    tract to the microbial flocs in waste water treatment facilities. Microbial biofilms may however also cause a wide range of industrial and medical problems, and have been implicated in a wide range of persistent infectious diseases, including implantassociated microbial infections. Bacterial adhesion...... is the first committing step in biofilm formation, and has therefore been intensely scrutinized. Much however, still remains elusive. Bacterial adhesion is a highly complex process, which is influenced by a variety of factors. In this thesis, a range of physico-chemical, molecular and environmental parameters......, which influence the transition from a planktonic lifestyle to a sessile lifestyle, have been studied. Protein conditioning film formation was found to influence bacterial adhesion and subsequent biofilm formation considerable, and an aqueous extract of fish muscle tissue was shown to significantly...

  2. Cell adhesion molecules: detection with univalent second antibody

    OpenAIRE

    1980-01-01

    Identification of cell surface molecules that play a role in cell-cell adhesion (here called cell adhesion molecules) has been achieved by demonstrating the inhibitory effect of univalent antibodies that bind these molecules in an in vitro assay of cell-cell adhesion. A more convenient reagent, intact (divalent) antibody, has been avoided because it might agglutinate the cells rather than blocking cell-cell adhesion. In this report, we show that intact rabbit immunoglobulin directed against c...

  3. Several domains from VAR2CSA can induce Plasmodium falciparum adhesion-blocking antibodies

    DEFF Research Database (Denmark)

    Salanti, Ali; Resende, Mafalda; Ditlev, Sisse B;

    2010-01-01

    ABSTRACT: BACKGROUND: Malaria caused by Plasmodium falciparum can result in several different syndromes with severe clinical consequences for the about 200 million individuals infected each year. During pregnancy, women living in endemic areas become susceptible to malaria due to lack of antibodies...

  4. Full-length recombinant Plasmodium falciparum VAR2CSA binds specifically to CSPG and induces potent parasite adhesion blocking antibodies

    DEFF Research Database (Denmark)

    Khunrae, Pongsak; Dahlbäck, Madeleine; Nielsen, Morten A;

    2010-01-01

    Plasmodium falciparum malaria remains one of the world's leading causes of human suffering and poverty. Each year, the disease takes 1-3 million lives, mainly in sub-Saharan Africa. The adhesion of parasite-infected erythrocytes to the vascular endothelium or the placenta is the key event...

  5. New adhesive systems based on functionalized block copolymers

    Energy Technology Data Exchange (ETDEWEB)

    Kent, M.; Saunders, R.; Hurst, M.; Small, J.; Emerson, J.; Zamora, D.

    1997-05-01

    The goal of this work was to evaluate chemically-functionalized block copolymers as adhesion promoters for metal/thermoset resin interfaces. Novel block copolymers were synthesized which contain pendant functional groups reactive toward copper and epoxy resins. In particular, imidazole and triazole functionalities that chelate with copper were incorporated onto one block, while secondary amines were incorporated onto the second block. These copolymers were found to self-assemble from solution onto copper surfaces to form monolayers. The structure of the adsorbed monolayers were studied in detail by neutron reflection and time-of-flight secondary ion mass spectrometry. The monolayer structure was found to vary markedly with the solution conditions and adsorption protocol. Appropriate conditions were found for which the two blocks form separate layers on the surface with the amine functionalized block exposed at the air surface. Adhesion testing of block copolymer-coated copper with epoxy resins was performed in both lap shear and peel modes. Modest enhancements in bond strengths were observed with the block copolymer applied to the native oxide. However, it was discovered that the native oxide is the weak link, and that by simply removing the native oxide, and then applying an epoxy resin before the native oxide can reform, excellent bond strength in the as-prepared state as well as excellent retention of bond strength after exposure to solder in ambient conditions are obtained. It is recommended that long term aging studies be performed with and without the block copolymer. In addition, the functionalized block copolymer method should be evaluated for another system that has inherently poor bonding, such as the nickel/silicone interface, and for systems involving metals and alloys which form oxides very rapidly, such as aluminum and stainless steel, where bonding strategies involve stabilizing the native oxide.

  6. Monoclonal antibody to murine PECAM-1 (CD31) blocks acute inflammation in vivo

    OpenAIRE

    1994-01-01

    A murine model of peritonitis was used to test the role of platelet/endothelial cell adhesion molecule 1 (PECAM-1/CD31) in acute inflammation. A monoclonal antibody (mAb) specific for murine PECAM-1 injected intravenously 4 h before the intraperitoneal injection of thioglycollate broth blocked leukocyte emigration into the peritoneal cavity for up to 48 h. This block was particularly evident for neutrophils. Control mAb, including one that bound to murine CD18 without blocking its function, f...

  7. Adhesion between peptides/antibodies and breast cancer cells

    Science.gov (United States)

    Meng, J.; Paetzell, E.; Bogorad, A.; Soboyejo, W. O.

    2010-06-01

    Atomic force microscopy (AFM) techniques were used to measure the adhesion forces between the receptors on breast cancer cells specific to human luteinizing hormone-releasing hormone (LHRH) peptides and antibodies specific to the EphA2 receptor. The adhesion forces between LHRH-coated AFM tips and human MDA-MB-231 cells (breast cancer cells) were shown to be about five times greater than those between LHRH-coated AFM tips and normal Hs578Bst breast cells. Similarly, those between EphA2 antibody-coated AFM tips and breast cancer cells were over five times greater than those between EphA2 antibody-coated AFM tips and normal breast cells. The results suggest that AFM can be used for the detection of breast cancer cells in biopsies. The implications of the results are also discussed for the early detection and localized treatment of cancer.

  8. [Anti-Ro/SSA antibodies in congenital heart block].

    Science.gov (United States)

    Barrios Prieto, Ernesto; Martínez Ceccopieri, David Alejandro; Panduro Barón, J Guadalupe; Fajardo Dueñas, Sergio

    2012-06-01

    Describe a case of a female patient having anti-Ro/SSA antibodies without any other risk factor or collagen disease. In her first pregnancy a congenital heart block and hydrops in the fetus were diagnosed, and these caused stillbirth. In a second pregnancy an in utero treatment resulted in the succesful delivery of a normal child.

  9. The NTS-DBL2X region of VAR2CSA Induces cross-reactive antibodies that inhibit adhesion of several Plasmodium falciparum isolates to chondroitin sulfate A

    DEFF Research Database (Denmark)

    Bigey, Pascal; Gnidehou, Sédami; Doritchamou, Justin;

    2011-01-01

    -adapted parasite lines and field isolates expressing VAR2CSA. Competition enzyme-linked immunosorbent assay (ELISA) was employed to analyze functional resemblance between antibodies induced in animals and those naturally acquired by immune multigravidae. Results. Antibodies targeting the N-terminal sequence (NTS......) up to DBL2X (NTS-DBL2X) efficiently blocked parasite adhesion to chondroitin sulfate A in a manner similar to that of antibodies raised against the entire VAR2CSA extracellular domain. Interestingly, naturally acquired antibodies and those induced by vaccination against NTS-DBL2X target overlapping...

  10. Integrin-blocking antibodies delay keratinocyte re-epithelialization in a human three-dimensional wound healing model.

    Directory of Open Access Journals (Sweden)

    Christophe Egles

    Full Text Available The alpha6beta4 integrin plays a significant role in tumor growth, angiogenesis and metastasis through modulation of growth factor signaling, and is a potentially important therapeutic target. However, alpha6beta4-mediated cell-matrix adhesion is critical in normal keratinocyte attachment, signaling and anchorage to the basement membrane through its interaction with laminin-5, raising potential risks for targeted therapy. Bioengineered Human Skin Equivalent (HSE, which have been shown to mimic their normal and wounded counterparts, have been used here to investigate the consequences of targeting beta4 to establish toxic effects on normal tissue homeostasis and epithelial wound repair. We tested two antibodies directed to different beta4 epitopes, one adhesion-blocking (ASC-8 and one non-adhesion blocking (ASC-3, and determined that these antibodies were appropriately localized to the basal surface of keratinocytes at the basement membrane interface where beta4 is expressed. While normal tissue architecture was not altered, ASC-8 induced a sub-basal split at the basement membrane in non-wounded tissue. In addition, wound closure was significantly inhibited by ASC-8, but not by ASC-3, as the epithelial tongue only covered 40 percent of the wound area at 120 hours post-wounding. These results demonstrate beta4 adhesion-blocking antibodies may have adverse effects on normal tissue, whereas antibodies directed to other epitopes may provide safer alternatives for therapy. Taken together, we conclude that these three-dimensional tissue models provide a biologically relevant platform to identify toxic effects induced by candidate therapeutics, which will allow generation of findings that are more predictive of in vivo responses early in the drug development process.

  11. CD47-blocking antibodies restore phagocytosis and prevent atherosclerosis.

    Science.gov (United States)

    Kojima, Yoko; Volkmer, Jens-Peter; McKenna, Kelly; Civelek, Mete; Lusis, Aldons Jake; Miller, Clint L; Direnzo, Daniel; Nanda, Vivek; Ye, Jianqin; Connolly, Andrew J; Schadt, Eric E; Quertermous, Thomas; Betancur, Paola; Maegdefessel, Lars; Matic, Ljubica Perisic; Hedin, Ulf; Weissman, Irving L; Leeper, Nicholas J

    2016-08-01

    Atherosclerosis is the disease process that underlies heart attack and stroke. Advanced lesions at risk of rupture are characterized by the pathological accumulation of diseased vascular cells and apoptotic cellular debris. Why these cells are not cleared remains unknown. Here we show that atherogenesis is associated with upregulation of CD47, a key anti-phagocytic molecule that is known to render malignant cells resistant to programmed cell removal, or 'efferocytosis'. We find that administration of CD47-blocking antibodies reverses this defect in efferocytosis, normalizes the clearance of diseased vascular tissue, and ameliorates atherosclerosis in multiple mouse models. Mechanistic studies implicate the pro-atherosclerotic factor TNF-α as a fundamental driver of impaired programmed cell removal, explaining why this process is compromised in vascular disease. Similar to recent observations in cancer, impaired efferocytosis appears to play a pathogenic role in cardiovascular disease, but is not a fixed defect and may represent a novel therapeutic target. PMID:27437576

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    microenvironment, making it an attractive target for anti-cancer therapy. In this study, we produced a function-blocking anti-S100A4 monoclonal antibody with metastasis-suppressing activity. Antibody treatment significantly reduced metastatic burden in the lungs of experimental animals by blocking the recruitment...

  13. Using engineered single-chain antibodies to correlate molecular binding properties and nanoparticle adhesion dynamics.

    Science.gov (United States)

    Haun, Jered B; Pepper, Lauren R; Boder, Eric T; Hammer, Daniel A

    2011-11-15

    Elucidation of the relationship between targeting molecule binding properties and the adhesive behavior of therapeutic or diagnostic nanocarriers would aid in the design of optimized vectors and lead to improved efficacy. We measured the adhesion of 200-nm-diameter particles under fluid flow that was mediated by a diverse array of molecular interactions, including recombinant single-chain antibodies (scFvs), full antibodies, and the avidin/biotin interaction. Within the panel of scFvs, we used a family of mutants that display a spectrum of binding kinetics, allowing us to compare nanoparticle adhesion to bond chemistry. In addition, we explored the effect of molecular size by inserting a protein linker into the scFv fusion construct and by employing scFvs that are specific for targets with vastly different sizes. Using computational models, we extracted multivalent kinetic rate constants for particle attachment and detachment from the adhesion data and correlated the results to molecular binding properties. Our results indicate that the factors that increase encounter probability, such as adhesion molecule valency and size, directly enhance the rate of nanoparticle attachment. Bond kinetics had no influence on scFv-mediated nanoparticle attachment within the kinetic range tested, however, but did appear to affect antibody/antigen and avidin/biotin mediated adhesion. We attribute this finding to a combination of multivalent binding and differences in bond mechanical strength between recombinant scFvs and the other adhesion molecules. Nanoparticle detachment probability correlated directly with adhesion molecule valency and size, as well as the logarithm of the affinity for all molecules tested. On the basis of this work, scFvs can serve as viable targeting receptors for nanoparticles, but improvements to their bond mechanical strength would likely be required to fully exploit their tunable kinetic properties and maximize the adhesion efficiency of nanoparticles that

  14. Amine-containing block copolymers: long-term adhesion promoters and corrosion resistant coatings

    Energy Technology Data Exchange (ETDEWEB)

    Small, J.H.; Saunders, R.S.; Kent, M.S.

    1996-07-01

    Arylamine-containing diblock copolymers were prepared via ring- opening metathesis polymerization (ROMP) to afford well-defined phase- separated materials. Alteration of the functionaity in a block, as well as the size of the blocks, allowed for the synthesis of self- assembled monolayers on a copper surface. The arylamine-containing block exhibited a strong binding affinity for the copper surface as seen by neutron reflectivity experiments. In addition, neutron reflectivity data verifies the self-assembly of block copolymer monolayers normal to the copper surface. Block copolymers prepared in this manner allow for the preparation of a wide range of adhesives and corrosion resistant materials. The use of ring-opening metathesis polymerization is important because it permits the synthesis of a variety of functionalized block copolymers.

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

    Science.gov (United States)

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

    1995-10-01

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

  16. A completely transparent, adhesively bonded soda-lime glass block masonry system

    Directory of Open Access Journals (Sweden)

    Faidra Oikonomopoulou

    2015-06-01

    Full Text Available A pioneering, all transparent, self-supporting glass block facade is presented in this paper. Previously realized examples utilize embedded metal components in order to obtain the desired structural performance despite the fact that these elements greatly affect the facade’s overall transparency level. Undeniably, the oxymoron ‘transparency and strength’ remains the prime concern in such applications. In this paper, a new, innovative structural system for glass block facades is described, which demonstrably meets both criteria. The structure is exclusively constructed by monolithic glass blocks, bonded with a colourless, UV-curing adhesive, obtaining thus a maximum transparency. In addition, the desired structural performance is achieved solely through the masonry system, without any opaque substructure. Differing from previous realized projects, solid soda-lime glass blocks are used rather than borosilicate ones. This article provides an overview of the integrated architectural and structural design and discusses the choice of materials. The structural verification of the system is demonstrated. The results show that the adhesively bonded glass block structure has the required self-structural behaviour, but only if strict tolerances are met in the geometry of the glass blocks.  

  17. A completely transparent, adhesively bonded soda-lime glass block masonry system

    Directory of Open Access Journals (Sweden)

    F. Oikonomopoulou

    2015-01-01

    Full Text Available A pioneering, all transparent, self-supporting glass block facade is presented in this paper. Previously realized examples utilize embedded metal components in order to obtain the desired structural performance despite the fact that these elements greatly affect the facade’s overall transparency level. Undeniably, the oxymoron ‘transparency and strength’ remains the prime concern in such applications. In this paper, a new, innovative structural system for glass block facades is described, which demonstrably meets both criteria. The structure is exclusively constructed by monolithic glass blocks, bonded with a colourless, UV-curing adhesive, obtaining thus a maximum transparency. In addition, the desired structural performance is achieved solely through the masonry system, without any opaque substructure. Differing from previous realized projects, solid soda-lime glass blocks are used rather than borosilicate ones. This article provides an overview of the integrated architectural and structural design and discusses the choice of materials. The structural verification of the system is demonstrated. The results show that the adhesively bonded glass block structure has the required self-structural behaviour, but only if strict tolerances are met in the geometry of the glass blocks.

  18. Effect of Curing Mode on Shear Bond Strength of Self-Adhesive Cement to Composite Blocks

    OpenAIRE

    Jin-Young Kim; Ga-Young Cho; Byoung-Duck Roh; Yooseok Shin

    2016-01-01

    To overcome the disadvantages of computer-aided design/computer-aided manufacturing (CAD/CAM) processed indirect restorations using glass-ceramics and other ceramics, resin nano ceramic, which has high strength and wear resistance with improved polish retention and optical properties, was introduced. The purpose of this study was to evaluate the shear bond strength and fracture pattern of indirect CAD/CAM composite blocks cemented with two self-etch adhesive cements with different curing mode...

  19. Significance of the conformation of building blocks in curing of barnacle underwater adhesive.

    Science.gov (United States)

    Kamino, Kei; Nakano, Masahiro; Kanai, Satoru

    2012-05-01

    Barnacles are a unique sessile crustacean that attach irreversibly and firmly to foreign underwater surfaces. Its biological underwater adhesive is a peculiar extracellular multi-protein complex. Here we characterize one of the two major proteins, a 52 kDa protein found in the barnacle cement complex. Cloning of the cDNA revealed that the protein has no homolog in the nonredundant database. The primary structure consists of four long sequence repeats. The process of dissolving the protein at the adhesive joint of the animal by various treatments was monitored in order to obtain insight into the molecular mechanism involved in curing of the adhesive bulk. Treatments with protein denaturant, reducing agents and/or chemical-specific proteolysis in combination with 2D diagonal PAGE indicated no involvement of the protein in intermolecular cross-linkage/polymerization, including formation of intermolecular disulfide bonds. As solubilization of the proteins required high concentrations of denaturing agents, it appears that both the conformation of the protein as building blocks and non-covalent molecular interactions between the building blocks, possibly hydrophobic interactions and hydrogen bonds, are crucial for curing of the cement. It was also suggested that the protein contributes to surface coupling by an anchoring effect to micro- to nanoscopic roughness of surfaces.

  20. Remission of congenital complete heart block without anti-Ro/La antibodies: A case report

    Directory of Open Access Journals (Sweden)

    Souvik Mitra

    2013-01-01

    Full Text Available Anti-Ro/La negative congenital heart block (CHB is uncommon. We report one such case of CHB, with no associated structural heart disease or maternal autoantibodies. The heart block reverted to sinus rhythm spontaneously at two weeks of age, and the patient remains in sinus rhythm at a one year followup. Whether patients with antibody negative complete heart block have a different clinical course is conjectural.

  1. Remission of congenital complete heart block without anti-Ro/La antibodies: A case report.

    Science.gov (United States)

    Mitra, Souvik; Saha, Anindya Kumar; Sardar, Syamal Kumar; Singh, Arun Kumarendu

    2013-07-01

    Anti-Ro/La negative congenital heart block (CHB) is uncommon. We report one such case of CHB, with no associated structural heart disease or maternal autoantibodies. The heart block reverted to sinus rhythm spontaneously at two weeks of age, and the patient remains in sinus rhythm at a one year followup. Whether patients with antibody negative complete heart block have a different clinical course is conjectural.

  2. Role of CD18-dependent and CD18-independent mechanisms in the increased leukocyte adhesiveness and in the variations of circulating white blood cell populations induced by anti-CD3 monoclonal antibodies.

    Science.gov (United States)

    Kinnaert, P; Pradier, O; Bournonville, B; Habrant, C; Goldman, M; Van Geertruyden, N

    1996-01-01

    Anti-CD3 antibodies induce a quick and profound depletion of peripheral blood mononuclear cells (PBMCs) that is not well understood. We studied the effect of OKT3, a mouse monoclonal antibody against the human CD3 complex, on the in vitro adhesion of human PBMCs to monolayers of fresh and fixed human umbilical vein endothelial cells (HUVECs). OKT3 induced an increased adhesiveness of PBMCs. This phenomenon was blocked with anti-CD18 antibodies, indicating the participation of beta 2 integrins. As this increased adhesiveness could explain the lymphopenia by adhesion of PBMCs to endothelial cells and their sequestration in some peripheral vascular beds, we studied the effect of anti-CD18 antibodies in vivo on mice injected with 145/2C11, a hamster monoclonal antibody against murine CD3. Mice treated with 145/2C11 presented with a transient granulocytopenia and a sustained reduction in PBMCs. A monoclonal anti-CD18 antibody prevented the granulocytopenia but had no effect on the drop in PBMCs. Consequently, the in vivo depletion of PBMCs after administration of an anti-CD3 monoclonal antibody involves CD18-independent mechanisms, while the transient drop in polymorphonuclear cells appears to be CD18-dependent. PMID:8819275

  3. A function blocking anti-mouse integrin α5β1 antibody inhibits angiogenesis and impedes tumor growth in vivo

    Directory of Open Access Journals (Sweden)

    Powers David

    2007-11-01

    Full Text Available Abstract Background Integrins are important adhesion molecules that regulate tumor and endothelial cell survival, proliferation and migration. The integrin α5β1 has been shown to play a critical role during angiogenesis. An inhibitor of this integrin, volociximab (M200, inhibits endothelial cell growth and movement in vitro, independent of the growth factor milieu, and inhibits tumor growth in vivo in the rabbit VX2 carcinoma model. Although volociximab has already been tested in open label, pilot phase II clinical trials in melanoma, pancreatic and renal cell cancer, evaluation of the mechanism of action of volociximab has been limited because this antibody does not cross-react with murine α5β1, precluding its use in standard mouse xenograft models. Methods We generated a panel of rat-anti-mouse α5β1 antibodies, with the intent of identifying an antibody that recapitulated the properties of volociximab. Hybridoma clones were screened for analogous function to volociximab, including specificity for α5β1 heterodimer and blocking of integrin binding to fibronectin. A subset of antibodies that met these criteria were further characterized for their capacities to bind to mouse endothelial cells, inhibit cell migration and block angiogenesis in vitro. One antibody that encompassed all of these attributes, 339.1, was selected from this panel and tested in xenograft models. Results A panel of antibodies was characterized for specificity and potency. The affinity of antibody 339.1 for mouse integrin α5β1 was determined to be 0.59 nM, as measured by BIAcore. This antibody does not significantly cross-react with human integrin, however 339.1 inhibits murine endothelial cell migration and tube formation and elicits cell death in these cells (EC50 = 5.3 nM. In multiple xenograft models, 339.1 inhibited the growth of established tumors by 40–60% (p Conclusion The results herein demonstrate that 339.1, like volociximab, exhibits potent anti-α5β1

  4. Insulin action is blocked by a monoclonal antibody that inhibits insulin receptor kinase

    International Nuclear Information System (INIS)

    Thirty-six monoclonal antibodies to the human insulin receptor were produced. Thirty-four bound the intracellular domain of the receptor β subunit, the domain containing the tyrosine-specific kinase activity. Of these 34 antibodies, 33 recognized the rat receptor and 1 was shown to precipitate the receptors from mice, chickens and frogs with high affinity. Another of the antibodies inhibited the kinase activities of the human and frog receptors with equal potencies. This antibody inhibited the kinase activities of these receptors by more than 90%, whereas others had no effect on either kinase activity. Microinjection of the inhibiting antibody into Xenopus oocytes blocked the ability of insulin to stimulate oocyte maturation. In contrast, this inhibiting antibody did not block the ability of progesterone to stimulate the same response. Furthermore, control immunoglobulin and a noninhibiting antibody to the receptor β subunit did not block this response to insulin. These results strongly support a role for the tyrosine-specific kinase activity of the insulin receptor in mediating this biological effect of insulin

  5. Monoclonal antibodies to the human insulin receptor block insulin binding and inhibit insulin action.

    OpenAIRE

    Roth, R A; Cassell, D J; Wong, K. Y.; Maddux, B A; Goldfine, I D

    1982-01-01

    Antibodies to the insulin receptor were prepared in BALB/c mice by immunization with IM-9 human lymphocytes, a cell type that has a large number of plasma membrane insulin receptors. The spleens of these mice were then removed, and their lymphocytes were fused to a mouse myeloma cell line, FO cells. After screening over 1,200 resulting hybrids, one stable hybrid was obtained that produced IgG1 antibodies directed towards the insulin receptor. This antibody blocked 125I-labeled insulin binding...

  6. A human/mouse chimeric monoclonal antibody against intercellular adhesion molecule-1 for tumor radioimmunoimaging

    Energy Technology Data Exchange (ETDEWEB)

    Yamamura, Miyuki; Hinoda, Yuji; Sasaki, Shigeru; Tsujisaki, Masayuki; Imai, Kohzoh [Sapporo Medical Univ. (Japan); Oriuchi, Noboru; Endo, Keigo

    1996-04-01

    A mouse-human chimeric antibody for intercellular adhesion molecule-1 (ICAM-1) was established by using heavy chain loss mouse mutant hybridoma and human immunoglobulin expression vector. The HA58 hybridoma secreted anti-ICAM-1 monoclonal antibody (MoAb) (IgG1,{kappa}). The gene of the mouse variable region of heavy chain was amplified and cloned by the polymerase chain reaction technique directly from the HA58 hybridoma RNA. The variable region of heavy chain was joined with an expression vector which contains human {gamma}1 constant gene. The expression vector was transfected into heavy chain loss mutant cells HA58-7, which produced only murine immunoglobulin light chains. The resultant chimeric MoAb HA58, chHA58, retained full-binding reactivity to ICAM-1 compared with murine HA58 parental antibody. The chimeric MoAb chHA58 showed little antibody dependent cell-mediated cytotoxic activity against cultured tumor cells. Biodistribution studies with {sup 99m}Tc-labeled chHA58 in nude mice bearing human gastric carcinoma JRST cells, demonstrated that the tumor-blood ratio was 1.55 at 18 h after injection, when the tumors were clearly visible in gamma scintigraphy. These data suggest that chHA58 may be of practical use for radioimmunoimaging of a wide variety of tumors. (author).

  7. [Neonatal lupus erythematosus: complete atrioventricular block and SSA/Ro antibodies].

    Science.gov (United States)

    Prados, R; Maroto, E; López Longo, J; Monteagudo, I; Carreño, L; García, E J

    1987-06-01

    A newborn boy with complete A-V block and positive anti-SSA/Ro antibodies is reported. Authors comment on pathological findings of neonatal lupus erythematosus. They also review prognosis and clinical course and point out management of these patients before and after birth.

  8. The effect of antibodies against cell-surface adhesion molecules (LFA-1{alpha} and ICAM-1) on the migration and localization of {sup 99m}Tc-labeled leukocytes in acute infection

    Energy Technology Data Exchange (ETDEWEB)

    Amartey, J.K.; Parhar, R.S.; Al-Sedairy, S.T

    1997-08-01

    The deficiency of adhesion molecules on leukocytes could severely impair their ability to migrate and perform effective immunological functions leading to clinical situations such as LAD (leukocyte adhesion deficiency) syndrome. We investigated the effects of blocking anti-LFA-1{alpha} and ICAM-1 antibody-treated {sup 99m}Tc-labeled leukocytes on the migration and localization to the site of E. coli-induced acute infection in CBA/J mice. A significant inhibition of migration and localization of antibody-treated leukocytes to the site of infection was observed, reaffirming the vital role of these adhesion molecules, especially during scintigraphic examination of patients for deep infections or abscess using labeled leukocytes.

  9. Murine anti-vaccinia virus D8 antibodies target different epitopes and differ in their ability to block D8 binding to CS-E.

    Directory of Open Access Journals (Sweden)

    Michael H Matho

    2014-12-01

    Full Text Available The IMV envelope protein D8 is an adhesion molecule and a major immunodominant antigen of vaccinia virus (VACV. Here we identified the optimal D8 ligand to be chondroitin sulfate E (CS-E. CS-E is characterized by a disaccharide moiety with two sulfated hydroxyl groups at positions 4' and 6' of GalNAc. To study the role of antibodies in preventing D8 adhesion to CS-E, we have used a panel of murine monoclonal antibodies, and tested their ability to compete with CS-E for D8 binding. Among four antibody specificity groups, MAbs of one group (group IV fully abrogated CS-E binding, while MAbs of a second group (group III displayed widely varying levels of CS-E blocking. Using EM, we identified the binding site for each antibody specificity group on D8. Recombinant D8 forms a hexameric arrangement, mediated by self-association of a small C-terminal domain of D8. We propose a model in which D8 oligomerization on the IMV would allow VACV to adhere to heterogeneous population of CS, including CS-C and potentially CS-A, while overall increasing binding efficiency to CS-E.

  10. Blocking Pseudomonas Aeruginosa, Chromobacterium Violaceum, and Ralstonia Solanacearum Adhesion by Fruit Glycans

    Directory of Open Access Journals (Sweden)

    Nechama Gilboa-Garber

    2014-05-01

    Full Text Available The soil-borne pathogens Pseudomonas aeruginosa, Chromobacterium violaceum, and Ralstonia solanacearum, possess the lectins PA-IL, PA-IIL, CV-IIL, RSL, and RS-IIL, which may mediate their adhesion onto animal and plant target cells, enabling infections. Such infections may be prevented by surrounding the sensitive cells with competing glycans, which act as glycodecoys that block patholectins and capture pathogens that bear them. The above-mentioned five lectins have been used by us as probes to reveal progeny-protecting glycodecoys in avian eggs, milk, royal jelly, and seeds. Herein we describe their usage as probes for fruit and onion glycodecoys. They revealed lectin-blocking galactosides, fructose, oligo/polysaccharides, and glycoproteins in most of the examined fruits. Galactose/arabinose- bearing compounds were detected by PA-IL in banana, carob, pineapple, pomegranate, kiwifruit, and dates. Diverse mannose/fucose-bearing compounds were detected by PA-IIL in banana, onion, and pomegranate; by CV-IIL in pineapple; by RSL in banana, carob, date, onion, and pineapple, and by RS-IIL in date and fig. The results show the high efficiency of these lectins as probes for natural infection-preventing glycodecoys. Usage of fruit and seed embryo-protecting glycodecoys, unless allergenic, is advantageous for preventing animal intestinal and external and plant wilting infections since they are natural, harmless, inexpensive, and widely available.

  11. Adhesion

    Science.gov (United States)

    As the body moves, tissues or organs inside are normally able to shift around each other. This is because these tissues have ... occur if the adhesions cause an organ or body part to: Twist Pull ... unable to move normally The risk of forming adhesions is high ...

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

    Science.gov (United States)

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

    2016-03-01

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

  13. Cytoskeletal inhibitors, anti-adhesion molecule antibodies, and lectins inhibit hepatocyte spheroid formation.

    Directory of Open Access Journals (Sweden)

    Nakamura M

    2002-02-01

    Full Text Available We investigated the role of cytoskeletons, adhesion molecules, membrane-glycosylations, and proteoglycans in forming the shape of adult rat hepatocyte spheroids. Isolated hepatocytes were cultured on dishes coated with chondroitin sulfate phosphatidyl ethanolamine (CS-PE. Spheroid-forming ability was observed after adding cytoskeletal inhibitors (cytochalasin D, colchicine, okadaic acid, mycalolide B, anti-adhesion molecule antibodies (anti-E-cadherin, anti-connexin 32, anti-zo-1, a glycosphingolipid synthetic inhibitor (N-butyldeoxynojirimycin, a proteoglycan synthetic inhibitor (p-nitrophenyl-beta-D-xylopyranoside, and several lectins. Localization of actin was studied using confocal microscopy after rhodamine-phalloidin staining. Adding cytoskeletal inhibitors on the initial day resulted in weakly clustered cell aggregates rather than smoothly formed spheroids. These effects disappeared at lower reagent concentrations. When reagents were added on day 3, after the formation of spheroids, only mycalolide B was associated with an irregular spheroid surface; the others had no effect. Adding the anti-E-cadherin, anti-connexin 32 on the initial day showed inhibition of spheroid formation, but anti-zo-1 and proteoglycan synthetic inhibitor had no effects. Among the several lectins, only Wheat Germ Agglutinin (WGA, Ricinus communis Agglutinin I (RCA-I, and Concanavalin A (ConA showed inhibition. These results suggest that cytoskeletal conformation and some adhesion molecules are necessary to form spheroids. Based on the interactions between lectins and hepatocytes in the present study, hepatocytes appear to contain an N-linked complex or N-linked hybrid glycosylated chains.

  14. A liquid phase blocking ELISA for the detection of antibodies against infectious bronchitis virus

    Directory of Open Access Journals (Sweden)

    Cardoso T.C.

    1999-01-01

    Full Text Available A liquid phase blocking ELISA (LPB-ELISA was developed for the detection and measurement of antibodies against infectious bronchitis virus (IBV. The purified and nonpurified virus used as antigen, the capture and detector antibodies, and the chicken hyperimmune sera were prepared and standardized for this purpose. A total of 156 sera from vaccinated and 100 from specific pathogen-free chickens with no recorded contact with the virus were tested. The respective serum titers obtained in the serum neutralization test (SNT were compared with those obtained in the LPB-ELISA. There was a high correlation (r2 = 0.8926 between the two tests. The LPB-ELISA represents a single test suitable for the rapid detection of antibodies against bronchitis virus in chicken sera, with good sensitivity (88%, specificity (100% and agreement (95.31%.

  15. Microstructured Block Copolymer Surfaces for Control of Microbe Adhesion and Aggregation

    Directory of Open Access Journals (Sweden)

    Ryan R. Hansen

    2014-03-01

    Full Text Available The attachment and arrangement of microbes onto a substrate is influenced by both the biochemical and physical surface properties. In this report, we develop lectin-functionalized substrates containing patterned, three-dimensional polymeric structures of varied shapes and densities and use these to investigate the effects of topology and spatial confinement on lectin-mediated microbe immobilization. Films of poly(glycidyl methacrylate-block-4,4-dimethyl-2-vinylazlactone (PGMA-b-PVDMA were patterned on silicon surfaces into line arrays or square grid patterns with 5 μm wide features and varied pitch. The patterned films had three-dimensional geometries with 900 nm film thickness. After surface functionalization with wheat germ agglutinin, the size of Pseudomonas fluorescens aggregates immobilized was dependent on the pattern dimensions. Films patterned as parallel lines or square grids with a pitch of 10 μm or less led to the immobilization of individual microbes with minimal formation of aggregates. Both geometries allowed for incremental increases in aggregate size distribution with each increase in pitch. These engineered surfaces combine spatial confinement with affinity-based capture to control the extent of microbe adhesion and aggregation, and can also be used as a platform to investigate intercellular interactions and biofilm formation in microbial populations of controlled sizes.

  16. Development of a blocking latex agglutination test for the detection of antibodies to chicken anemia virus.

    Science.gov (United States)

    Trinh, Dai Quang; Ogawa, Haruko; Bui, Vuong Nghia; Nguyen, Tham Thi Hong; Gronsang, Dulyatad; Baatartsogt, Tugsbaatar; Kizito, Mugimba Kahoza; AboElkhair, Mohammed; Yamaguchi, Shigeo; Nguyen, Viet Khong; Imai, Kunitoshi

    2015-09-01

    A blocking latex agglutination test (b-LAT) developed in this study was evaluated for the detection of antibodies against chicken anemia virus (CAV) in chickens. Polystyrene latex beads were coupled with a neutralizing monoclonal antibody (mAb) to CAV (mAb-beads). When mAb-beads were mixed with antigens prepared from the lysate of MDCC-MSB1 cells infected with CAV, agglutination occurred. A short pre-incubation of CAV antigens with CAV-specific antiserum inhibited the agglutination of mAb-beads. The test results were obtained within 5min. The specificity of b-LAT was evaluated using sera from specific pathogen-free chickens and sera containing antibodies to avian influenza virus, Newcastle disease virus, infectious bursal disease virus, and Marek's disease virus; nonspecific agglutination and cross-reactivity with antibodies to unrelated viruses were not observed. The examination of 94 serum samples collected from commercial breeder chickens of various ages (17-63 weeks) revealed good agreement (93.6%, Kappa value=0.82) between b-LAT and a virus neutralization test, known to be most sensitive and specific in the detection of antibodies to CAV. These results indicate that b-LAT, a simple and rapid test, is a useful and reliable tool in CAV serology.

  17. Development of a blocking latex agglutination test for the detection of antibodies to chicken anemia virus.

    Science.gov (United States)

    Trinh, Dai Quang; Ogawa, Haruko; Bui, Vuong Nghia; Nguyen, Tham Thi Hong; Gronsang, Dulyatad; Baatartsogt, Tugsbaatar; Kizito, Mugimba Kahoza; AboElkhair, Mohammed; Yamaguchi, Shigeo; Nguyen, Viet Khong; Imai, Kunitoshi

    2015-09-01

    A blocking latex agglutination test (b-LAT) developed in this study was evaluated for the detection of antibodies against chicken anemia virus (CAV) in chickens. Polystyrene latex beads were coupled with a neutralizing monoclonal antibody (mAb) to CAV (mAb-beads). When mAb-beads were mixed with antigens prepared from the lysate of MDCC-MSB1 cells infected with CAV, agglutination occurred. A short pre-incubation of CAV antigens with CAV-specific antiserum inhibited the agglutination of mAb-beads. The test results were obtained within 5min. The specificity of b-LAT was evaluated using sera from specific pathogen-free chickens and sera containing antibodies to avian influenza virus, Newcastle disease virus, infectious bursal disease virus, and Marek's disease virus; nonspecific agglutination and cross-reactivity with antibodies to unrelated viruses were not observed. The examination of 94 serum samples collected from commercial breeder chickens of various ages (17-63 weeks) revealed good agreement (93.6%, Kappa value=0.82) between b-LAT and a virus neutralization test, known to be most sensitive and specific in the detection of antibodies to CAV. These results indicate that b-LAT, a simple and rapid test, is a useful and reliable tool in CAV serology. PMID:25952731

  18. Scintigraphic findings of the thyroid in hypothyroid patients with blocking-type TSH-receptor antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Kasagi, K. (Dept. of Nuclear Medicine, Kyoto Univ. Hospital (Japan)); Hatabu, H. (Dept. of Nuclear Medicine, Kyoto Univ. Hospital (Japan)); Miyamoto, S. (Dept. of Nuclear Medicine, Kyoto Univ. Hospital (Japan)); Takeuchi, R. (Dept. of Nuclear Medicine, Kyoto Univ. Hospital (Japan)); Misaki, T. (Dept. of Nuclear Medicine, Kyoto Univ. Hospital (Japan)); Sakahara, H. (Dept. of Nuclear Medicine, Kyoto Univ. Hospital (Japan)); Iida, Y. (Dept. of Nuclear Medicine, Kyoto Univ. Hospital (Japan)); Konishi, J. (Dept. of Nuclear Medicine, Kyoto Univ. Hospital (Japan))

    1994-09-01

    The present study was designed to analyse the scintigraphic appearance of the thyroid in hypothyroid patients with blocking-type TSH receptor antibodies (TRAbs). Eleven hypothyroid patients with autoimmune thyroiditis positive for TSH binding inhibitor immunoglobulins (TBII) [80% [+-] 12 (SD)%; normal <11%] and for thyroid stimulation-blocking antibodies (TSBAbs) (90% [+-] 9%; normal <32%) were studied. Thyroid scanning was performed using technetium-99m or iodine-123, when the patients were hypothyroid. Analysis of the scan images revealed the presence of localized functioning areas in six patients (group 1), and no visualization of the thyroid in the remaining five patients (group 2). Patients in group 1 showed significantly higher uptake of [sup 99m]Tc than those in group 2 (P<0.05). Interestingly, three patients in group 1 were positive for thyroid-stimulating antibodies (TSAbs) (249% [+-] 17%; normal <145%), which were not detected in the remaining eight patients. Antibodies against thyroglobulin and microsomal antigens were detected in nine (81.8%) and 11 (100%) patients, respectively, but neither of these titres correlated with the scan image. Three patients in group 1 underwent scintigraphy again after treatment with thyroxine, at which time the functioning lesion was not noted. Fourteen hypothyroid patients with negative TBII displayed no such scintigraphic findings. Chronic stimulation of the thyroid by TSAbs and/or TSH might be responsible for the presence of the functioning lesion, but clarification of the mechanism requires further studies. In summary (1) TSAbs were detected in three (27.3%) of 11 hypothyroid patients with blocking TRAbs; (2) thyroid scintigraphy revealed the presence of localized functioning area(s) in approximately half of these cases. (orig.)

  19. Evaluation of a blocking ELISA for the detection of antibodies against Lawsonia intracellularis in pig sera

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    Merza Malik

    2011-04-01

    Full Text Available Abstract Background Lawsonia intracellularis is a common cause of chronic diarrhoea and poor performance in young growing pigs. Diagnosis of this obligate intracellular bacterium is based on the demonstration of the microbe or microbial DNA in tissue specimens or faecal samples, or the demonstration of L. intracellularis-specific antibodies in sera. The aim of the present study was to evaluate a blocking ELISA in the detection of serum antibodies to L. intracellularis, by comparison to the previously widely used immunofluorescent antibody test (IFAT. Methods Sera were collected from 176 pigs aged 8-12 weeks originating from 24 herds with or without problems with diarrhoea and poor performance in young growing pigs. Sera were analyzed by the blocking ELISA and by IFAT. Bayesian modelling techniques were used to account for the absence of a gold standard test and the results of the blocking ELISA was modelled against the IFAT test with a "2 dependent tests, 2 populations, no gold standard" model. Results At the finally selected cut-off value of percent inhibition (PI 35, the diagnostic sensitivity of the blocking ELISA was 72% and the diagnostic specificity was 93%. The positive predictive value was 0.82 and the negative predictive value was 0.89, at the observed prevalence of 33.5%. Conclusion The sensitivity and specificity as evaluated by Bayesian statistic techniques differed from that previously reported. Properties of diagnostic tests may well vary between countries, laboratories and among populations of animals. In the absence of a true gold standard, the importance of validating new methods by appropriate statistical methods and with respect to the target population must be emphasized.

  20. Ultrasound-guided continuous suprascapular nerve block for adhesive capsulitis: one case and a short topical review

    DEFF Research Database (Denmark)

    Neimann, Jens Dupont Børglum; Bartholdy, Anne; Hautopp, H;

    2011-01-01

    impact passive and guided active mobilization by the performing physiotherapist for three consecutive weeks. This case and a short topical review on the use of SSN block in painful shoulder conditions highlight the possibility of a USG continuous nerve block of the SSN as sufficient pain management......We present a case with an ultrasound-guided (USG) placement of a perineural catheter beneath the transverse scapular ligament in the scapular notch to provide a continuous block of the suprascapular nerve (SSN). The patient suffered from a severe and very painful adhesive capsulitis of the left...... shoulder secondary to an operation in the same shoulder conducted 20 weeks previously for impingement syndrome and a superior labral anterior-posterior tear. Following a new operation with capsular release, the placement of a continuous nerve block catheter subsequently allowed for nearly pain-free low...

  1. Scintigraphic findings of the thyroid in hypothyroid patients with blocking-type TSH-receptor antibodies

    International Nuclear Information System (INIS)

    The present study was designed to analyse the scintigraphic appearance of the thyroid in hypothyroid patients with blocking-type TSH receptor antibodies (TRAbs). Eleven hypothyroid patients with autoimmune thyroiditis positive for TSH binding inhibitor immunoglobulins (TBII) [80% ± 12 (SD)%; normal 99mTc than those in group 2 (P<0.05). Interestingly, three patients in group 1 were positive for thyroid-stimulating antibodies (TSAbs) (249% ± 17%; normal <145%), which were not detected in the remaining eight patients. Antibodies against thyroglobulin and microsomal antigens were detected in nine (81.8%) and 11 (100%) patients, respectively, but neither of these titres correlated with the scan image. Three patients in group 1 underwent scintigraphy again after treatment with thyroxine, at which time the functioning lesion was not noted. Fourteen hypothyroid patients with negative TBII displayed no such scintigraphic findings. Chronic stimulation of the thyroid by TSAbs and/or TSH might be responsible for the presence of the functioning lesion, but clarification of the mechanism requires further studies. In summary (1) TSAbs were detected in three (27.3%) of 11 hypothyroid patients with blocking TRAbs; (2) thyroid scintigraphy revealed the presence of localized functioning area(s) in approximately half of these cases. (orig.)

  2. Var2CSA DBL6-epsilon domain expressed in HEK293 induces limited cross-reactive and blocking antibodies to CSA binding parasites

    Directory of Open Access Journals (Sweden)

    Scherf Artur

    2008-09-01

    Full Text Available Abstract Background Pregnancy-associated malaria (PAM is a serious consequence of Plasmodium falciparum-infected erythrocytes sequestration in the placenta through the adhesion to the placental receptor chondroitin sulfate A (CSA. Although women become resistant to PAM as they acquire transcending inhibitory immunity against CSA-binding parasites, hundreds of thousands of lives could be saved if a prophylactic vaccine targeting the surface proteins of placental parasites could be designed. Recent works point to the variant protein var2CSA as the key target for the development of a pregnancy-associated malaria vaccine. However, designing such a prophylactic vaccine has been hindered by the difficulty in identifying regions of var2CSA that could elicit broadly neutralizing and adhesion-blocking antibodies. Methods Var2CSA is a very large protein with an estimated molecular weight of 350 kDa, and can be divided into six cysteine rich Duffy binding-like domains (DBL. The human embryonic kidney 293 cell line (HEK293 was used to produce secreted soluble recombinant forms of var2CSA DBL domains. The Escherichia coli expression system was also assessed for the domains not expressed or expressed in low amount in the HEK293 system. To investigate whether var2CSA binding DBL domains can induce biologically active antibodies recognizing the native var2CSA and blocking the interaction, mice were immunized with the refolded DBL3-X or the HEK293 secreted DBL6-ε domains. Results Using the HEK293 expression system, DBL1-X, DBL4-ε and DBL6-ε were produced at relatively high levels in the culture supernatant, while DBL3-X and DBL5-ε were produced at much lower levels. DBL2-X and DBL3-X domains were obtained after refolding of the inclusion bodies produced in E. coli. Importantly, mice antisera raised against the recombinant DBL6-ε domain, specifically reacted against the surface of CSA-binding parasites and revealed adhesion blocking activity. Conclusion This

  3. Mucosal Antibodies Induced by Intranasal but Not Intramuscular Immunization Block Norovirus GII.4 Virus-Like Particle Receptor Binding.

    Science.gov (United States)

    Tamminen, Kirsi; Malm, Maria; Vesikari, Timo; Blazevic, Vesna

    2016-06-01

    Noroviruses (NoVs) account for the majority of diagnosed cases of viral acute gastroenteritis worldwide. Virus-like particle (VLP)-based vaccines against NoV are currently under development. Serum antibodies that block the binding of NoV VLPs to histo-blood group antigens, the putative receptors for NoV, correlate with protection against NoV infection. The role of functional mucosal antibodies in protection is largely unknown, even though the intestinal mucosa is the entry port for NoV. Balb/c mice were immunized intramuscularly (IM) or intranasally (IN) with NoV GII.4 VLPs, and systemic and mucosal blocking antibody responses were studied. IN immunization elicited NoV-specific serum and mucosal IgG and IgA antibodies, whereas IM immunized animals completely lacked IgA. Both immunization routes induced similar blocking activity in serum but only IN route generated blocking antibodies in mucosa. The level of IgA in the mucosal (nasal) lavages strongly correlated (r = 0.841) with the blocking activity, suggesting that IgA, but not IgG, is the major NoV blocking antibody on mucosal surfaces. The results indicate that only mucosal immunization route induces the development of functional anti-NoV IgA on mucosal surface. PMID:27135874

  4. Development of a sensitive and specific epitope-blocking ELISA for universal detection of antibodies to human enterovirus 71 strains.

    Directory of Open Access Journals (Sweden)

    Fang He

    Full Text Available BACKGROUND: Human Enterovirus 71 (EV71 is a common cause of hand, foot and mouth disease (HFMD in young children. It is often associated with severe neurological diseases and mortalities in recent outbreaks across the Asia Pacific region. Currently, there is no efficient universal antibody test available to detect EV71 infections. METHODOLOGY/PRINCIPAL FINDING: In the present study, an epitope-blocking ELISA was developed to detect specific antibodies to human EV71 viruses in human or animal sera. The assay relies on a novel monoclonal antibody (Mab 1C6 that specifically binds to capsid proteins in whole EV71 viruses without any cross reaction to any EV71 capsid protein expressed alone. The sensitivity and specificity of the epitope-blocking ELISA for EV71 was evaluated and compared to microneutralization using immunized animal sera to multiple virus genotypes of EV71 and coxsackieviruses. Further, 200 serum sample from human individuals who were potentially infected with EV71 viruses were tested in both the blocking ELISA and microneutralization. Results indicated that antibodies to EV71 were readily detected in immunized animals or human sera by the epitope blocking ELISA whereas specimens with antibodies to other enteroviruses yielded negative results. This assay is not only simpler to perform but also shows higher sensitivity and specificity as compared to microneutralization. CONCLUSION: The epitope-blocking ELISA based on a unique Mab 1C6 provided highly sensitive and 100% specific detection of antibodies to human EV71 viruses in human sera.

  5. Ultrasound findings in fetal congenital heart block associated with maternal anti-Ro/SSA and Anti-La/SSB antibodies.

    Science.gov (United States)

    Lai, Jasmine; Clark, Toshi J; Tan, Justin H; Delaney, Shani; Jolley, Jennifer A

    2015-03-01

    We present the sonographic features of a second-trimester fetus diagnosed with a bradyarrhythmia at 19 weeks' gestation. The mother carried a diagnosis of Sjögren syndrome, including the presence of SSA and SSB antibodies. Ultrasound M-mode and fetal echocardiogram revealed the etiology of the bradycardia to be a complete fetal congenital heart block, likely due to transplacental passage of autoimmune anti-Ro/SSA and anti-La/SSB antibodies. Consequential to the congenital heart block, the fetus developed hydrops fetalis at 21 weeks' gestational age. We discuss the 2 major etiologies of congenital heart block and the implications in subsequent pregnancies.

  6. Inhibition of insulitis and prevention of diabetes in nonobese diabetic mice by blocking L-selectin and very late antigen 4 adhesion receptors.

    OpenAIRE

    Yang, X D; Karin, N; Tisch, R; Steinman, L; McDevitt, H O

    1993-01-01

    Leukocyte adhesion to the endothelial venules in the pancreatic islets is thought to be one of the initial steps in the development of insulin-dependent diabetes mellitus. It has been suggested that leukocyte adhesion to endothelium is a sequential multistep process involving various different homing receptors. We report here that blocking different homing receptors--namely, L-selectin and very late antigen 4 (VLA-4)--which function during different stages of the adhesion process, by specific...

  7. Different binding of stimulatory-type and blocking-type TSH receptor antibody with guinea-pig testis membrane.

    Science.gov (United States)

    Inui, T; Ochi, Y; Hachiya, T; Chen, W; Nakajima, Y; Kajita, Y; Ogura, H

    1991-11-01

    A receptor assay using [125I]bTSH-binding to guinea-pig testis membrane was developed. Unlabelled hCG and FSH inhibited [125I]bTSH binding. In patients with Graves' disease and in untreated hyperthyroid patients, almost all long-acting thyroid stimulators and thyroid-stimulating antibodies, respectively did not inhibit [125I]bTSH binding, which on the other hand was inhibited by thyroid stimulation blocking antibodies in patients with primary hypothyroidism. When the inhibitory effect on the binding of [125I]hCG and 125I-synthetic alpha-subunit peptide (alpha 26-46) of hCG to testis membrane was examined, bTSH resulted in a significant inhibition. However, all three kinds of TSH receptor antibodies had no inhibitory effect. This study demonstrated 1. interaction of alpha-subunit of TSH and hCG with the testicular receptor; 2. binding of thyroid stimulation-blocking antibody and lack of binding of thyroid-stimulating antibody to the testicular TSH receptor in spite of binding of these TSH receptor antibodies to the thyroidal TSH receptor, and 3. lack of binding of thyroid-stimulating antibody and thyroid stimulation-blocking antibody to the testicular gonadotropin receptor. PMID:1684686

  8. Sensitive assay to detect thyroid stimulating antibody (TSAb) in the presence of thyroid stimulation blocking antibody (TSBAb) in serum.

    Science.gov (United States)

    Ochi, Y; Yamashiro, K; Takasu, N; Kajita, Y; Sato, Y; Nagata, A

    2001-02-01

    The detection of thyroid stimulating antibody (TSAb) activity in the presence of thyroid stimulation blocking antibody (TSBAb) in Graves' serum is difficult because TSBAb blocks TSAb activity. We recently demonstrated that polyethylene glycol (PEG) augments TSAb activity in porcine thyroid cells (PTC) assay. This PEG-induced augmentation makes it possible to develop a sensitive assay to detect TSAb in the presence of TSBAb. We studied the effects of PEG on TSAb- and TSBAb-activities in PTC using 4 different preparations of the samples; (1) crude IgG using PEG 22.5% precipitated fraction (PF) from Graves' serum (0.2 ml), (2) crude IgG using PEG 12.5% PF, (3) serum (50 microl), and (4) serum (50 microl) in the presence of 5% PEG (final). When the effects of PEG on TSAb activity using crude IgG were examined, PEG 22.5% PF showed significantly higher TSAb activity than PEG 12.5% PF as reported previously. The augmentative effect of PEG on TSAb activity was also observed by the addition of 5% PEG to serum. We also demonstrated that PEG augmented TSAb-activities even in TSBAb-positive serum by two methods (crude IgG using PEG 22.5% PF and the addition of 5% PEG to serum). TSBAb activities were expressed by two calculation methods (A= [1 - (a - b)/(c - d) x 100] and B = [1 - (a - d)/(c - d) x 100], where a is cAMP produced in the presence of bTSH and patient's IgG, b is cAMP produced in the presence of patient's IgG, c is cAMP produced in the presence of bTSH and normal IgG, and d is cAMP produced in the presence of normal IgG). In the presence of TSAb, the values of A method were always higher than those of B method, since TSAb stimulated cAMP synthesis. We have developed two sensitive methods to detect TSAb even in the presence of TSBAb in serum using PEG; 1) incubation of crude IgG using PEG 22.5% PF from serum (0.2 ml), and 2) co-incubation of 5 % PEG with test serum (50 microl). PMID:11294493

  9. A Novel Blocking ELISA for Detection of Antibodies against Hepatitis E Virus in Domestic Pigs.

    Science.gov (United States)

    Chen, Yiyang; Zhao, Qin; Liu, Baoyuan; Wang, Lizhen; Sun, Yani; Li, Huixia; Wang, Xinjie; Syed, Shahid Faraz; Zhang, Gaiping; Zhou, En-Min

    2016-01-01

    Hepatitis E virus (HEV) infects both humans and animals, with an overall human mortality rate generally less than 1%, but as high as 20% among pregnant women. HEV strains fall into 4 major genotypes. Zoonotic genotypes 3 and 4 associate with sporadic human and animal HEV cases in many industrialized countries. To date, collective evidence implicates pigs as the main HEV reservoir, justifying the importance of monitoring HEV infection rates in pig herds to prevent human illness. Due to the lack of a robust in vitro cell culture system for viral propagation, no "gold standard" assay has yet been developed to detect HEV infection in domestic pigs. 1E4, a monoclonal antibody (mAb) specific for the C-terminal 268 amino acids of HEV genotype 4 ORF2 capsid protein (sORF2-C), was generated and conjugated to horseradish peroxidase (HRP) for use in a blocking ELISA (bELISA). Optimal sORF2-C coating antigen concentration (8 μg/ml), HRP-1E4 dilution (1:1000), and test pig serum dilution (1:20) were determined using a checkerboard titration test. A cut-off value of 16.9% was chosen to differentiate between positive vs. negative sera after mean percent inhibition (PI) testing of 230 negative pig sera. Compared with the indirect ELISA (iELISA), western blot, and a commercial ELISA kit for detecting anti-HEV antibodies in human sera, the bELISA showed no statistical differences and statistically high coincidence of 93.23%, 92%, and 95% with the other tests, respectively. A blocking ELISA (bELISA) for detecting anti-HEV antibodies in pig serum samples was developed with high sensitivity and high specificity comparable to that of the indirect ELISA. The bELISA results exhibited high agreement with iELISA, western blot, and a commercial ELISA kit designed to detect human anti-HEV antibodies. Therefore, bELISA should serve as an ideal method for large-scale serological investigation of anti-HEV antibodies in domestic pigs.

  10. A Novel Blocking ELISA for Detection of Antibodies against Hepatitis E Virus in Domestic Pigs.

    Directory of Open Access Journals (Sweden)

    Yiyang Chen

    Full Text Available Hepatitis E virus (HEV infects both humans and animals, with an overall human mortality rate generally less than 1%, but as high as 20% among pregnant women. HEV strains fall into 4 major genotypes. Zoonotic genotypes 3 and 4 associate with sporadic human and animal HEV cases in many industrialized countries. To date, collective evidence implicates pigs as the main HEV reservoir, justifying the importance of monitoring HEV infection rates in pig herds to prevent human illness. Due to the lack of a robust in vitro cell culture system for viral propagation, no "gold standard" assay has yet been developed to detect HEV infection in domestic pigs. 1E4, a monoclonal antibody (mAb specific for the C-terminal 268 amino acids of HEV genotype 4 ORF2 capsid protein (sORF2-C, was generated and conjugated to horseradish peroxidase (HRP for use in a blocking ELISA (bELISA. Optimal sORF2-C coating antigen concentration (8 μg/ml, HRP-1E4 dilution (1:1000, and test pig serum dilution (1:20 were determined using a checkerboard titration test. A cut-off value of 16.9% was chosen to differentiate between positive vs. negative sera after mean percent inhibition (PI testing of 230 negative pig sera. Compared with the indirect ELISA (iELISA, western blot, and a commercial ELISA kit for detecting anti-HEV antibodies in human sera, the bELISA showed no statistical differences and statistically high coincidence of 93.23%, 92%, and 95% with the other tests, respectively. A blocking ELISA (bELISA for detecting anti-HEV antibodies in pig serum samples was developed with high sensitivity and high specificity comparable to that of the indirect ELISA. The bELISA results exhibited high agreement with iELISA, western blot, and a commercial ELISA kit designed to detect human anti-HEV antibodies. Therefore, bELISA should serve as an ideal method for large-scale serological investigation of anti-HEV antibodies in domestic pigs.

  11. INHIBITION OF Acinetobacter baumannii ADHESION BY ANTI-FIMBRIAL ANTIBODY: THE FIMBRIAL ANTIGEN EFFECTIVENESS

    Directory of Open Access Journals (Sweden)

    Hadeel K. Musafer

    2013-01-01

    , concentrations of (25, 50 μg/ml of fimbriae extract caused a significant increase (P≤0.05 noticed in the average of T-cells forming the active T-Rosette (41.3, 54.3% and the total (62, 81% compared with control which reached (28.3, 40.6% respectively. The present study results revealed an increase in phagocytosis of killed yeast cells by phagocytes. To our knowledge this is the first preliminary report in Iraq showed the role of fimbriated A. baumannii in adherence on epithelial cell and inhibition of this adhesion by specific antibody, also this report investigated the role of fimbrial antigen on some immune cell.

  12. Anti-neutrophil cytoplasmic antibody-enriched IgG induces adhesion of human T lymphocytes to extracellular matrix proteins.

    Science.gov (United States)

    Tomer, Y; Lider, O; Gilburd, B; Hershkoviz, R; Meroni, P L; Wiik, A; Shoenfeld, Y

    1997-06-01

    Recent studies have shown that anti-neutrophil cytoplasmic antibodies (ANCA) can activate neutrophils to adhere to endothelium, degranulate, and cause endothelial cell injury. These data have lead to the hypothesis that the T cell inflammatory response causing the vasculitis in Wegener's granulomatosis (WG) is secondary to stimulation of neutrophils by ANCA. So far there is no evidence for a direct effect of ANCA on lymphocytes. The present study was designed to examine whether lymphocytes can be directly stimulated by ANCA to adhere to endothelial extracellular matrix (ECM) proteins. Human and mouse ANCA-enriched IgG were tested for their ability to increase adhesion of human T lymphocytes to fibronectin, laminin, and intact ECM. Incubation of human T lymphocytes with human ANCA-enriched IgG increased adhesion of the lymphocytes in a dose-dependent manner to fibronectin, laminin, and intact ECM (the percentage adhesion to intact ECM was 55.7 +/- 3.1 and 45.0 +/- 1.0% for lymphocytes incubated with human IgG containing ANCA or control human IgG, respectively; P = 0.0045). The same induction of adhesion to fibronectin, laminin, and intact ECM was observed when the cells were incubated with the F(ab)2 fragment of ANCA-enriched IgG. Similarly, ANCA-enriched IgG produced in mice increased the adhesion of lymphocytes to fibronectin (the percentage adhesion to fibronectin was 29.7 +/- 4.3 and 16.6 +/- 1.9% for lymphocytes incubated with mouse IgG-ANCA or control mouse IgG, respectively; P = 0.0008). These results may suggest that ANCA can directly stimulate lymphocytes to adhere to endothelial ECM and to induce the vasculitic lesions of WG. It remains to be shown by which mechanisms ANCA stimulate lymphocytes to adhere to ECM. PMID:9175913

  13. Generation and characterization of function-blocking anti-ectodysplasin A (EDA) monoclonal antibodies that induce ectodermal dysplasia.

    Science.gov (United States)

    Kowalczyk-Quintas, Christine; Willen, Laure; Dang, Anh Thu; Sarrasin, Heidi; Tardivel, Aubry; Hermes, Katharina; Schneider, Holm; Gaide, Olivier; Donzé, Olivier; Kirby, Neil; Headon, Denis J; Schneider, Pascal

    2014-02-14

    Development of ectodermal appendages, such as hair, teeth, sweat glands, sebaceous glands, and mammary glands, requires the action of the TNF family ligand ectodysplasin A (EDA). Mutations of the X-linked EDA gene cause reduction or absence of many ectodermal appendages and have been identified as a cause of ectodermal dysplasia in humans, mice, dogs, and cattle. We have generated blocking antibodies, raised in Eda-deficient mice, against the conserved, receptor-binding domain of EDA. These antibodies recognize epitopes overlapping the receptor-binding site and prevent EDA from binding and activating EDAR at close to stoichiometric ratios in in vitro binding and activity assays. The antibodies block EDA1 and EDA2 of both mammalian and avian origin and, in vivo, suppress the ability of recombinant Fc-EDA1 to rescue ectodermal dysplasia in Eda-deficient Tabby mice. Moreover, administration of EDA blocking antibodies to pregnant wild type mice induced in developing wild type fetuses a marked and permanent ectodermal dysplasia. These function-blocking anti-EDA antibodies with wide cross-species reactivity will enable study of the developmental and postdevelopmental roles of EDA in a variety of organisms and open the route to therapeutic intervention in conditions in which EDA may be implicated. PMID:24391090

  14. Generation and Characterization of Function-blocking Anti-ectodysplasin A (EDA) Monoclonal Antibodies That Induce Ectodermal Dysplasia*

    Science.gov (United States)

    Kowalczyk-Quintas, Christine; Willen, Laure; Dang, Anh Thu; Sarrasin, Heidi; Tardivel, Aubry; Hermes, Katharina; Schneider, Holm; Gaide, Olivier; Donzé, Olivier; Kirby, Neil; Headon, Denis J.; Schneider, Pascal

    2014-01-01

    Development of ectodermal appendages, such as hair, teeth, sweat glands, sebaceous glands, and mammary glands, requires the action of the TNF family ligand ectodysplasin A (EDA). Mutations of the X-linked EDA gene cause reduction or absence of many ectodermal appendages and have been identified as a cause of ectodermal dysplasia in humans, mice, dogs, and cattle. We have generated blocking antibodies, raised in Eda-deficient mice, against the conserved, receptor-binding domain of EDA. These antibodies recognize epitopes overlapping the receptor-binding site and prevent EDA from binding and activating EDAR at close to stoichiometric ratios in in vitro binding and activity assays. The antibodies block EDA1 and EDA2 of both mammalian and avian origin and, in vivo, suppress the ability of recombinant Fc-EDA1 to rescue ectodermal dysplasia in Eda-deficient Tabby mice. Moreover, administration of EDA blocking antibodies to pregnant wild type mice induced in developing wild type fetuses a marked and permanent ectodermal dysplasia. These function-blocking anti-EDA antibodies with wide cross-species reactivity will enable study of the developmental and postdevelopmental roles of EDA in a variety of organisms and open the route to therapeutic intervention in conditions in which EDA may be implicated. PMID:24391090

  15. Antibody against early driver of neurodegeneration cis P-tau blocks brain injury and tauopathy.

    Science.gov (United States)

    Kondo, Asami; Shahpasand, Koorosh; Mannix, Rebekah; Qiu, Jianhua; Moncaster, Juliet; Chen, Chun-Hau; Yao, Yandan; Lin, Yu-Min; Driver, Jane A; Sun, Yan; Wei, Shuo; Luo, Man-Li; Albayram, Onder; Huang, Pengyu; Rotenberg, Alexander; Ryo, Akihide; Goldstein, Lee E; Pascual-Leone, Alvaro; McKee, Ann C; Meehan, William; Zhou, Xiao Zhen; Lu, Kun Ping

    2015-07-23

    Traumatic brain injury (TBI), characterized by acute neurological dysfunction, is one of the best known environmental risk factors for chronic traumatic encephalopathy and Alzheimer's disease, the defining pathologic features of which include tauopathy made of phosphorylated tau protein (P-tau). However, tauopathy has not been detected in the early stages after TBI, and how TBI leads to tauopathy is unknown. Here we find robust cis P-tau pathology after TBI in humans and mice. After TBI in mice and stress in vitro, neurons acutely produce cis P-tau, which disrupts axonal microtubule networks and mitochondrial transport, spreads to other neurons, and leads to apoptosis. This process, which we term 'cistauosis', appears long before other tauopathy. Treating TBI mice with cis antibody blocks cistauosis, prevents tauopathy development and spread, and restores many TBI-related structural and functional sequelae. Thus, cis P-tau is a major early driver of disease after TBI and leads to tauopathy in chronic traumatic encephalopathy and Alzheimer's disease. The cis antibody may be further developed to detect and treat TBI, and prevent progressive neurodegeneration after injury. PMID:26176913

  16. Ultrasound-guided continuous suprascapular nerve block for adhesive capsulitis: one case and a short topical review.

    Science.gov (United States)

    Børglum, J; Bartholdy, A; Hautopp, H; Krogsgaard, M R; Jensen, K

    2011-02-01

    We present a case with an ultrasound-guided (USG) placement of a perineural catheter beneath the transverse scapular ligament in the scapular notch to provide a continuous block of the suprascapular nerve (SSN). The patient suffered from a severe and very painful adhesive capsulitis of the left shoulder secondary to an operation in the same shoulder conducted 20 weeks previously for impingement syndrome and a superior labral anterior-posterior tear. Following a new operation with capsular release, the placement of a continuous nerve block catheter subsequently allowed for nearly pain-free low impact passive and guided active mobilization by the performing physiotherapist for three consecutive weeks. This case and a short topical review on the use of SSN block in painful shoulder conditions highlight the possibility of a USG continuous nerve block of the SSN as sufficient pain management in the immediate post-operative period following capsular release of the shoulder. Findings in other painful shoulder conditions and suggestions for future studies are discussed in the text. PMID:21226866

  17. A completely transparent, adhesively bonded soda-lime glass block masonry system

    OpenAIRE

    Faidra Oikonomopoulou; Fred Veer; Rob Nijsse; K. Baardolf

    2015-01-01

    A pioneering, all transparent, self-supporting glass block facade is presented in this paper. Previously realized examples utilize embedded metal components in order to obtain the desired structural performance despite the fact that these elements greatly affect the facade’s overall transparency level. Undeniably, the oxymoron ‘transparency and strength’ remains the prime concern in such applications. In this paper, a new, innovative structural system for glass block facades is described, whi...

  18. Evaluation of a blocking ELISA for screening of antibodies against porcine reproductive and respiratory syndrome (PRRS) virus

    DEFF Research Database (Denmark)

    Sørensen, K.J.; Bøtner, Anette; Madsen, E.S.;

    1997-01-01

    A blocking Elisa was developed for the detection of antibodies against PRRS virus with a view to satisfying the need for examination of blood samples on a large scale. The test was evaluated in comparison with an indirect Elisa and the immunoperoxidase monolayer assay. The blocking Elisa...... was sensitive and specific. It had a higher capacity and was cheaper to perform than the immunoperoxidase monolayer assay and the indirect Elisa. It was comparable to the immunoperoxidase monolayer assay and better than the indirect Elisa in detecting antibodies formed early after infection, and it was superior...... to both the immunoperoxidase monolayer assay and the indirect Elisa in detecting antibodies at a late stage of infection....

  19. Generation of a haptoglobin-hemoglobin complex-specific Fab antibody blocking the binding of the complex to CD163

    DEFF Research Database (Denmark)

    Horn, Ivo R; Nielsen, Marianne Jensby; Madsen, Mette;

    2003-01-01

    During intravascular hemolysis hemoglobin (Hb) binds to haptoglobin (Hp) leading to endocytosis of the complex by the macrophage receptor, CD163. In the present study, we used a phage-display Fab antibody strategy to explore if the complex formation between Hp and Hb leads to exposure of antigenic...... epitopes specific for the complex. By Hp-Hb-affinity screening of a phage-Fab library, we isolated a phage clone against the ligand complex. Surface plasmon resonance analyses of the Fab part expressed as a recombinant protein revealed a high affinity binding (KD = 3.9 nm) to Hp-Hb, whereas no binding...... was measured for non-complexed Hp or Hb. The Fab antibody completely inhibited the binding of 125I-labeled Hp-Hb complexes to CD163 and blocked their uptake in CD163-transfected cells. In conclusion, we have raised a receptor-blocking antibody specifically recognizing the Hp-Hb complex. In addition to provide...

  20. Effect of different adhesive strategies on microtensile bond strength of computer aided design/computer aided manufacturing blocks bonded to dentin

    Science.gov (United States)

    Roperto, Renato; Akkus, Anna; Akkus, Ozan; Lang, Lisa; Sousa-Neto, Manoel Damiao; Teich, Sorin; Porto, Thiago Soares

    2016-01-01

    Background: The aim of this study was to determine the microtensile bond strength (μTBS) of ceramic and composite computer aided design-computer aided manufacturing (CAD-CAM) blocks bonded to dentin using different adhesive strategies. Materials and Methods: In this in vitro study, 30 crowns of sound freshly extracted human molars were sectioned horizontally 3 mm above the cementoenamel junction to produce flat dentin surfaces. Ceramic and composite CAD/CAM blocks, size 14, were sectioned into slices of 3 mm thick. Before bonding, CAD/CAM block surfaces were treated according to the manufacturer's instructions. Groups were created based on the adhesive strategy used: Group 1 (GI) - conventional resin cement + total-etch adhesive system, Group 2 (GII) - conventional resin cement + self-etch adhesive system, and Group 3 (GIII) - self-adhesive resin cement with no adhesive. Bonded specimens were stored in 100% humidity for 24h at 37΀C, and then sectioned with a slow-speed diamond saw to obtain 1 mm × 1 mm × 6 mm microsticks. Microtensile testing was then conducted using a microtensile tester. μTBS values were expressed in MPa and analyzed by one-way ANOVA with post hoc (Tukey) test at the 5% significance level. Results: Mean values and standard deviations of μTBS (MPa) were 17.68 (±2.71) for GI/ceramic; 17.62 (±3.99) for GI/composite; 13.61 (±6.92) for GII/composite; 12.22 (±4.24) for GII/ceramic; 7.47 (±2.29) for GIII/composite; and 6.48 (±3.10) for GIII/ceramic; ANOVA indicated significant differences among the adhesive modality and block interaction (P CAD/CAM restorations, either composite or ceramic, can be significantly affected by different adhesive strategies used. PMID:27076825

  1. Combination of neutralizing monoclonal antibodies against Hepatitis C virus E2 protein effectively blocks virus infection.

    Science.gov (United States)

    Bose, Mihika; Mullick, Ranajoy; Das, Soma; Das, Saumitra; Karande, Anjali A

    2016-09-15

    Hepatitis C virus (HCV) represents a major global health threat. The envelope glycoproteins, E1-E2 of HCV play an important role in infection by binding to hepatocyte surface receptors leading to viral entry. Several regions on the E1-E2 are conserved for maintaining structural stability, despite the high mutation rate of HCV. Identification of antigenic determinants in these domains would aid in the development of anti-virals. The present study was aimed to delineate neutralizing epitopes by generating monoclonal antibodies (mAbs) to envelope proteins that can block virus binding and entry. Using HCV-like particles (HCV-LPs) corresponding to genotype 3a (prevalent in India), we obtained three mAbs specific for the E2 protein that significantly inhibited virus binding to hepatoma cells. Using overlapping protein fragments and peptides of the E2 protein, the epitopes corresponding to the mAbs were delineated. MAbs H6D3 and A10F2 recognise sequential linear epitopes, whereas, mAb E3D8 recognises a discontinuous epitope. The epitope of mAb E3D8 overlaps with the CD81 receptor-binding site and that of mAb A10F2 with the hypervariable region 2 of the E2 protein. The epitopes corresponding to these mAbs are distinct and unique. A combination of these antibodies significantly inhibited HCV binding and entry in both HCV pseudoparticle (in vitro) and HCV cell culture (ex vivo) system compared to the mAbs alone (P<0.0001). In conclusion, our findings support the potential of employing a cocktail of neutralizing mAbs in the management of HCV infection. PMID:27574733

  2. Adhesion of human basophils, eosinophils, and neutrophils to interleukin 1-activated human vascular endothelial cells: contributions of endothelial cell adhesion molecules

    OpenAIRE

    1991-01-01

    Cytokines such as interleukin 1 (IL-1) promote adhesiveness in human umbilical vein endothelial cells for leukocytes including basophils, eosinophils, and neutrophils, and induce expression of adherence molecules including ICAM-1 (intercellular adhesion molecule-1), ELAM-1 (endothelial-leukocyte adhesion molecule-1), and VCAM-1 (vascular cell adhesion molecule-1). In the present study, blocking monoclonal antibodies (mAb) recognizing ICAM-1, ELAM-1, and VCAM-1 have been used to compare their ...

  3. A bispecific antibody effectively neutralizes all four serotypes of dengue virus by simultaneous blocking virus attachment and fusion.

    Science.gov (United States)

    Shi, Xin; Deng, Yongqiang; Wang, Huajing; Ji, Guanghui; Tan, Wenlong; Jiang, Tao; Li, Xiaofeng; Zhao, Hui; Xia, Tian; Meng, Yanchun; Wang, Chao; Yu, Xiaojie; Yang, Yang; Li, Bohua; Qin, E-De; Dai, Jianxin; Qin, Cheng-Feng; Guo, Yajun

    2016-01-01

    Although dengue virus (DENV) infection severely threatens the health of humans, no specific antiviral drugs are currently approved for clinical use against DENV infection. Attachment and fusion are 2 critical steps for the flavivirus infection, and the corresponding functional epitopes are located at E protein domain III (E-DIII) and domain II (E-DII), respectively. Here, we constructed a bispecific antibody (DVD-1A1D-2A10) based on the 2 well-characterized anti-DENV monoclonal antibodies 1A1D-2 (1A1D) and 2A10G6 (2A10). The 1A1D antibody binds E-DIII and can block the virus attaching to the cell surface, while the 2A10 antibody binds E-DII and is able to prevent the virus from fusing with the endosomal membrane. Our data showed that DVD-1A1D-2A10 retained the antigen-binding activity of both parental antibodies. Importantly, it was demonstrated to be significantly more effective at neutralizing DENV than its parental antibodies both in vitro and in vivo, even better than the combination of them. To eliminate the potential antibody-dependent enhancement (ADE) effect, this bispecific antibody was successfully engineered to prevent Fc-γ-R interaction. Overall, we generated a bispecific anti-DENV antibody targeting both attachment and fusion stages, and this bispecific antibody broadly neutralized all 4 serotypes of DENV without risk of ADE, suggesting that it has great potential as a novel antiviral strategy against DENV. PMID:26905804

  4. QUANTIFICATION OF GLOMERULAR EPITHELIAL-CELL ADHESION BY USING ANTI-DNA ANTIBODIES IN ELISA

    NARCIS (Netherlands)

    COERS, W; SMEENK, RJT; SALANT, DJ; WEENING, JJ

    1992-01-01

    A sensitive and reproducible microassay is described for quantification of adhesion of cells to matrix-coated 96-wells plates under different experimental conditions. For this purpose glomerular visceral epithelial cells (GVEC) were used. Attached GVEC were fixed with methanol and incubated with a m

  5. Potent neutralization of influenza A virus by a single-domain antibody blocking M2 ion channel protein.

    Directory of Open Access Journals (Sweden)

    Guowei Wei

    Full Text Available Influenza A virus poses serious health threat to humans. Neutralizing antibodies against the highly conserved M2 ion channel is thought to offer broad protection against influenza A viruses. Here, we screened synthetic Camel single-domain antibody (VHH libraries against native M2 ion channel protein. One of the isolated VHHs, M2-7A, specifically bound to M2-expressed cell membrane as well as influenza A virion, inhibited replication of both amantadine-sensitive and resistant influenza A viruses in vitro, and protected mice from a lethal influenza virus challenge. Moreover, M2-7A showed blocking activity for proton influx through M2 ion channel. These pieces of evidence collectively demonstrate for the first time that a neutralizing antibody against M2 with broad specificity is achievable, and M2-7A may have potential for cross protection against a number of variants and subtypes of influenza A viruses.

  6. Naturally acquired antibody responses to recombinant Pfs230 and Pfs48/45 transmission blocking vaccine candidates

    DEFF Research Database (Denmark)

    Jones, Sophie; Grignard, Lynn; Nebie, Issa;

    2015-01-01

    for the future evaluation of vaccine immunogenicity and efficacy in populations naturally exposed to malaria. METHODS: We determined naturally acquired antibody responses to the recombinant proteins Pfs48/45-10C and Pfs230-230CMB in children from three malaria endemic settings in Ghana, Tanzania and Burkina Faso......OBJECTIVES: Pfs48/45 and Pfs230 are Plasmodium falciparum sexual stage proteins and promising malaria transmission-blocking vaccine candidates. Antibody responses against these proteins may be naturally acquired and target antigens may be under selective pressure. This has consequences....... CONCLUSIONS: We conclude there are naturally acquired antibody responses to both vaccine candidates which have functional relevance by reducing the transmissibility of infected individuals. We identified genetic polymorphisms, in pfs48/45 which exhibited geographical specificity....

  7. Blocking junctional adhesion molecule C enhances dendritic cell migration and boosts the immune responses against Leishmania major.

    Directory of Open Access Journals (Sweden)

    Romain Ballet

    2014-12-01

    Full Text Available The recruitment of dendritic cells to sites of infections and their migration to lymph nodes is fundamental for antigen processing and presentation to T cells. In the present study, we showed that antibody blockade of junctional adhesion molecule C (JAM-C on endothelial cells removed JAM-C away from junctions and increased vascular permeability after L. major infection. This has multiple consequences on the output of the immune response. In resistant C57BL/6 and susceptible BALB/c mice, we found higher numbers of innate immune cells migrating from blood to the site of infection. The subsequent migration of dendritic cells (DCs from the skin to the draining lymph node was also improved, thereby boosting the induction of the adaptive immune response. In C57BL/6 mice, JAM-C blockade after L. major injection led to an enhanced IFN-γ dominated T helper 1 (Th1 response with reduced skin lesions and parasite burden. Conversely, anti JAM-C treatment increased the IL-4-driven T helper 2 (Th2 response in BALB/c mice with disease exacerbation. Overall, our results show that JAM-C blockade can finely-tune the innate cell migration and accelerate the consequent immune response to L. major without changing the type of the T helper cell response.

  8. Relation of maternal anti-Ro/La antibodies to aortic dilation in patients with congenital complete heart block.

    Science.gov (United States)

    Davey, Debra L; Bratton, Susan L; Bradley, David J; Yetman, Anji T

    2011-08-15

    An association between congenital complete atrioventricular block (cCAVB) and aortic dilation during childhood has recently been reported. We sought to further explore this relation with particular emphasis on the natural history of aortic abnormalities over time. The relation of maternal anti-Ro/La antibody status to the aortic size of children affected with cCAVB was also assessed. The patients were evaluated longitudinally with serial echocardiography. During a 15-year period, 62 patients at our institution were diagnosed with cCAVB, of whom 40% were exposed to maternal autoimmune antibodies and 35% were not. The antibody status in the remaining patients was unknown. The patients underwent 9.3 ± 6.5 echocardiograms during the follow-up period. Dilation of the ascending aorta, defined as a z score >2.0, was present on the initial echocardiogram in all patients exposed to maternal antibodies and persisted during long-term follow-up in 96% of these patients. In contrast, 5% and 10% of patients without exposure to maternal autoimmune antibodies had aortic dilation on the initial and follow-up studies, respectively (p <0.001 and p <0.001, respectively). In conclusion, patients with autoimmune-mediated cCAVB merit periodic echocardiographic monitoring into adulthood to assess persistent or progressive aortic dilation and its attendant complications.

  9. A Therapeutic Antibody against West Nile Virus Neutralizes Infection by Blocking Fusion within Endosomes

    NARCIS (Netherlands)

    Thompson, Bruce S.; Moesker, Bastiaan; Smit, Jolanda M.; Wilschut, Jan; Diamond, Michael S.; Fremont, Daved H.

    2009-01-01

    Defining the precise cellular mechanisms of neutralization by potently inhibitory antibodies is important for understanding how the immune system successfully limits viral infections. We recently described a potently inhibitory monoclonal antibody (MAb E16) against the envelope (E) protein of West N

  10. Glossogyne tenuifolia Extract Inhibits TNF-α-Induced Expression of Adhesion Molecules in Human Umbilical Vein Endothelial Cells via Blocking the NF-kB Signaling Pathway.

    Science.gov (United States)

    Hsuan, Chin-Feng; Hsu, Hsia-Fen; Tseng, Wei-Kung; Lee, Thung-Lip; Wei, Yu-Feng; Hsu, Kwan-Lih; Wu, Chau-Chung; Houng, Jer-Yiing

    2015-01-01

    Chronic inflammation plays a pivotal role in the development of atherosclerosis, where the pro-inflammatory cytokine-induced expression of endothelial adhesion molecules and the recruitment of monocytes are the crucial events leading to its pathogenesis. Glossogyne tenuifolia ethanol extract (GTE) is shown to have potent anti-inflammatory and antioxidant activities. We evaluated the effects of GTE and its major components, luteolin (lut), luteolin-7-glucoside (lut-7-g), and oleanolic acid (OA) on TNF-α-induced expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs). The results demonstrated that GTE, lut, and lut-7-g attenuated the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in TNF-α-activated HUVECs, and inhibited the adhesion of monocytes to TNF-α-activated HUVECs. The TNF-α-induced mRNA expression of ICAM-1 and VCAM-1 was also suppressed, revealing their inhibitory effects at the transcriptional level. Furthermore, GTE, lut, and lut-7-g blocked the TNF-α-induced degradation of nuclear factor-kB inhibitor (IkB), an indicator of the activation of nuclear factor-kB (NF-kB). In summary, GTE and its bioactive components were effective in preventing the adhesion of monocytes to cytokine-activated endothelium by the inhibition of expression of adhesion molecules, which in turn is mediated through blocking the activation and nuclear translocation of NF-kB. The current results reveal the therapeutic potential of GTE in atherosclerosis. PMID:26393541

  11. Glossogyne tenuifolia Extract Inhibits TNF-α-Induced Expression of Adhesion Molecules in Human Umbilical Vein Endothelial Cells via Blocking the NF-kB Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Chin-Feng Hsuan

    2015-09-01

    Full Text Available Chronic inflammation plays a pivotal role in the development of atherosclerosis, where the pro-inflammatory cytokine-induced expression of endothelial adhesion molecules and the recruitment of monocytes are the crucial events leading to its pathogenesis. Glossogyne tenuifolia ethanol extract (GTE is shown to have potent anti-inflammatory and antioxidant activities. We evaluated the effects of GTE and its major components, luteolin (lut, luteolin-7-glucoside (lut-7-g, and oleanolic acid (OA on TNF-α-induced expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs. The results demonstrated that GTE, lut, and lut-7-g attenuated the expression of intercellular adhesion molecule-1 (ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1 in TNF-α-activated HUVECs, and inhibited the adhesion of monocytes to TNF-α-activated HUVECs. The TNF-α-induced mRNA expression of ICAM-1 and VCAM-1 was also suppressed, revealing their inhibitory effects at the transcriptional level. Furthermore, GTE, lut, and lut-7-g blocked the TNF-α-induced degradation of nuclear factor-kB inhibitor (IkB, an indicator of the activation of nuclear factor-kB (NF-kB. In summary, GTE and its bioactive components were effective in preventing the adhesion of monocytes to cytokine-activated endothelium by the inhibition of expression of adhesion molecules, which in turn is mediated through blocking the activation and nuclear translocation of NF-kB. The current results reveal the therapeutic potential of GTE in atherosclerosis.

  12. Characterization of Inhibitory Anti-insulin-like Growth Factor Receptor Antibodies with Different Epitope Specificity and Ligand-blocking Properties: IMPLICATIONS FOR MECHANISM OF ACTION IN VIVOS⃞

    OpenAIRE

    Doern, Adam; Cao, Xianjun; Sereno, Arlene; Reyes, Christopher L.; Altshuler, Angelina; Huang, Flora; Hession, Cathy; Flavier, Albert; Favis, Michael; Tran, Hon; Ailor, Eric; Levesque, Melissa; MURPHY, TRACEY; Berquist, Lisa; Tamraz, Susan

    2009-01-01

    Therapeutic antibodies directed against the type 1 insulin-like growth factor receptor (IGF-1R) have recently gained significant momentum in the clinic because of preliminary data generated in human patients with cancer. These antibodies inhibit ligand-mediated activation of IGF-1R and the resulting down-stream signaling cascade. Here we generated a panel of antibodies against IGF-1R and screened them for their ability to block the binding of both IGF-1 and IGF-2 at es...

  13. Neutralizing Monoclonal Antibodies Block Chikungunya Virus Entry and Release by Targeting an Epitope Critical to Viral Pathogenesis.

    Science.gov (United States)

    Jin, Jing; Liss, Nathan M; Chen, Dong-Hua; Liao, Maofu; Fox, Julie M; Shimak, Raeann M; Fong, Rachel H; Chafets, Daniel; Bakkour, Sonia; Keating, Sheila; Fomin, Marina E; Muench, Marcus O; Sherman, Michael B; Doranz, Benjamin J; Diamond, Michael S; Simmons, Graham

    2015-12-22

    We evaluated the mechanism by which neutralizing human monoclonal antibodies inhibit chikungunya virus (CHIKV) infection. Potently neutralizing antibodies (NAbs) blocked infection at multiple steps of the virus life cycle, including entry and release. Cryo-electron microscopy structures of Fab fragments of two human NAbs and chikungunya virus-like particles showed a binding footprint that spanned independent domains on neighboring E2 subunits within one viral spike, suggesting a mechanism for inhibiting low-pH-dependent membrane fusion. Detailed epitope mapping identified amino acid E2-W64 as a critical interaction residue. An escape mutation (E2-W64G) at this residue rendered CHIKV attenuated in mice. Consistent with these data, CHIKV-E2-W64G failed to emerge in vivo under the selection pressure of one of the NAbs, IM-CKV063. As our study suggests that antibodies engaging the residue E2-W64 can potently inhibit CHIKV at multiple stages of infection, antibody-based therapies or immunogens that target this region might have protective value.

  14. Bonding effectiveness of self-adhesive and conventional-type adhesive resin cements to CAD/CAM resin blocks. Part 2: Effect of ultrasonic and acid cleaning.

    Science.gov (United States)

    Kawaguchi, Asuka; Matsumoto, Mariko; Higashi, Mami; Miura, Jiro; Minamino, Takuya; Kabetani, Tomoshige; Takeshige, Fumio; Mine, Atsushi; Yatani, Hirofumi

    2016-01-01

    The present study assessed the effect of ultrasonic and acid cleaning on resin cement bonding to CAD/CAM resin blocks. One of two resin cements, PANAVIA V5 (PV5) or PANAVIA SA CEMENT HANDMIX (PSA), were bonded to one of 24 CAD/CAM blocks (KATANA AVENCIA BLOCK). Each cement group was divided into four subgroups: no cleaning (Ctl), ultrasonic cleaning (Uc), acid cleaning (Ac) and Uc+Ac. Micro-tensile bond strengths (µTBSs) were measured immediately and 1, 3, and 6 months after water storage. Block surfaces after each treatment were analyzed by scanning electron microscopy. Analysis of variance revealed a statistically significant effect for the parameters 'surface treatment' (psandblasting was effective in removing residual alumina particles, it did not affect the long-term bonding durability with non-contaminated CAD/CAM resin blocks. PMID:26830822

  15. Antidrug antibodies against TNF-blocking agents: correlations between disease activity, hypersensitivity reactions, and different classes of immunoglobulins

    Directory of Open Access Journals (Sweden)

    Benucci M

    2015-02-01

    : LDA 8% and NR 18% in the ADA group; in remission 3%, LDA 22%, and NR 10% in the ETN group; and LDA 6% and NR 16% in the IFX group (P=0.051. The percentages of patients with antidrug antibodies were: ADA 33.3%, ETN 11.5%, and IFX 10.3% (P=0.025; ADA versus ETN P=0.015. The percentages of patients with IgG4 antibodies were: ADA 6%, ETN 13%, and IFX 26% (P=0.017; ADA versus ETN P=0.437. Associations between antidrug antibodies, specific IgG4 antibodies, and adverse reactions were not significant for any of the three drugs. IgG4 levels were higher in the ADA group than in the other two groups, and higher in the patients with worse DAS28 (NR and in those experiencing adverse events. These data suggest a possible association between IgG4 levels and worse DAS28 (r2=5.8%, P=0.011. The presence of specific IgG4 antibodies against TNF blockers in patients with RA might affect the drugs’ activity. Patients with injection-site reactions and IgG4 against ETN may show a decreased response.Keywords: antidrug antibodies, TNF-blocking agents, IgG4 antibodies

  16. Expression of intercellular adhesion molecule-1 in rat heart with ischemia/reperfusion and limitation of infarct size by treatment with antibodies against cell adhesion molecules.

    OpenAIRE

    Yamazaki, T; Seko, Y; Tamatani, T; Miyasaka, M.; Yagita, H; Okumura, K.; R. Nagai; Yazaki, Y

    1993-01-01

    To elucidate the mechanism(s) of myocardial reperfusion injury, we investigated the roles of cell adhesion molecules on both leukocytes and vascular endothelial cells in the reperfused myocardia. We found that within 2 hours after reperfusion leukocytes began to infiltrate into the rat myocardia subjected to 30 minutes of ischemia and clarified, for the first time, that the expression of intercellular adhesion molecule-1 was enhanced on the capillary and venous endothelial cells from 8 to 96 ...

  17. A novel anti-EMMPRIN function-blocking antibody reduces T cell proliferation and neurotoxicity: relevance to multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Agrawal Smriti M

    2012-04-01

    Full Text Available Abstract Background Extracellular matrix metalloproteinase inducer (EMMPRIN; CD147, basigin is an inducer of the expression of several matrix metalloproteinases (MMPs. We reported previously that blocking EMMPRIN activity reduced neuroinflammation and severity of disease in an animal model of multiple sclerosis (MS, experimental autoimmune encephalomyelitis (EAE. Methods To improve upon EMMPRIN blockade, and to help unravel the biological functions of EMMPRIN in inflammatory disorders, we have developed several anti-EMMPRIN monoclonal antibodies. Results Of these monoclonal antibodies, a particular one, clone 10, was efficient in binding mouse and human cells using several methods of detection. The specificity of clone 10 was demonstrated by its lack of staining of EMMPRIN-null embryos compared to heterozygous and wild-type mouse samples. Functionally, human T cells activated with anti-CD3 and anti-CD28 elevated their expression of EMMPRIN and the treatment of these T cells with clone 10 resulted in decreased proliferation and matrix metalloproteinase- 9 (MMP-9 production. Activated human T cells were toxic to human neurons in culture and clone 10 pretreatment reduced T cell cytotoxicity correspondent with decrease of granzyme B levels within T cells. In vivo, EAE mice treated with clone 10 had a markedly reduced disease score compared to mice treated with IgM isotype control. Conclusions We have produced a novel anti-EMMPRIN monoclonal antibody that blocks several aspects of T cell activity, thus highlighting the multiple roles of EMMPRIN in T cell biology. Moreover, clone 10 reduces EAE scores in mice compared to controls, and has activity on human cells, potentially allowing for the testing of anti-EMMPRIN treatment not only in EAE, but conceivably also in MS.

  18. Antibody specificities of children living in a malaria endemic area to inhibitory and blocking epitopes on MSP-1 19 of Plasmodium falciparum.

    Science.gov (United States)

    Omosun, Y O; Adoro, S; Anumudu, C I; Odaibo, A B; Uthiapibull, C; Holder, A A; Nwagwu, M; Nwuba, R I

    2009-03-01

    Merozoite surface protein-1(19) (MSP-1(19)) specific antibodies which include processing inhibitory, blocking and neutral antibodies have been identified in individuals exposed to Plasmodium falciparum. Here we intend to look at the effect of single and multiple amino acid substitutions of MSP-1(19) on the recognition by polyclonal antibodies from children living in Igbo-Ora, Nigeria. This would provide us with information on the possibility of eliciting mainly processing inhibitory antibodies with a recombinant MSP-1(19) vaccine. Blood was collected from children in the rainy season and binding of anti-MSP-1(19) antibodies to modified mutants of MSP-1(19) was analysed by ELISA. The MSP-1(19) mutant proteins with single substitutions at positions 22 (Leu-->Arg), 43 (Glu-->Leu) and 53 (Asn-->Arg) and the MSP-1(19) mutant protein with multiple substitutions at positions 27+31+34+43 (Glu-->Tyr, Leu-->Arg, Tyr-->Ser, Glu-->Leu); which had inhibitory epitopes; had the highest recognition. Children recognised both sets of mutants with different age groups having different recognition levels. The percentage of malaria positive individuals (32-80%) with antibodies that bound to the mutants MSP-1(19) containing epitopes that recognise only processing inhibitory and not blocking antibodies, were significantly different from those with antibodies that did not bind to these mutants (21-28%). The amino acid substitutions that abolished the binding of blocking antibodies without affecting the binding of inhibitory antibodies are of particular interest in the design of MSP-1(19) based malaria vaccines. Although these MSP-1(19) mutants have not been found in natural population, their recognition by polyclonal antibodies from humans naturally infected with malaria is very promising for the future use of MSP-1(19) mutants in the design of a malaria vaccine. PMID:19081386

  19. Bonding effectiveness of self-adhesive and conventional-type adhesive resin cements to CAD/CAM resin blocks. Part 1: Effects of sandblasting and silanization.

    Science.gov (United States)

    Higashi, Mami; Matsumoto, Mariko; Kawaguchi, Asuka; Miura, Jiro; Minamino, Takuya; Kabetani, Tomoshige; Takeshige, Fumio; Mine, Atsushi; Yatani, Hirofumi

    2016-01-01

    The present study assessed the effect of sandblasting and silanization on resin cement bond strengths to CAD/CAM resin blocks. Twenty four blocks (KATANA AVENCIA BLOCK) were divided into two resin cement groups (PANAVIA V5 [PV5] and PANAVIA SA CEMENT HANDMIX [PSA]), and further divided into four subgroups representing different surface treatment methods: no treatment (Ctl), silanization (Si), sandblasting (Sb), and Sb+Si. After resin application, microtensile bond strengths (μTBSs) were measured immediately, 1, 3 and 6 months after water storage. In addition, surfaces resulting from each of the treatment methods were analyzed by scanning electron microscopy (SEM). Three-way analysis of variance revealed a statistically significant effect for the parameters 'surface treatment' (psandblasting roughened surfaces. PMID:26830821

  20. Antibodies from malaria-exposed pregnant women recognize trypsin resistant epitopes on the surface of Plasmodium falciparum-infected erythrocytes selected for adhesion to chondroitin sulphate A

    Directory of Open Access Journals (Sweden)

    Staalsoe Trine

    2004-09-01

    Full Text Available Abstract Background The ability of Plasmodium falciparum-infected erythrocytes to adhere to the microvasculature endothelium is thought to play a causal role in malaria pathogenesis. Cytoadhesion to endothelial receptors is generally found to be highly sensitive to trypsinization of the infected erythrocyte surface. However, several studies have found that parasite adhesion to placental receptors can be markedly less sensitive to trypsin. This study investigates whether chondroitin sulphate A (CSA binding parasites express trypsin-resistant variant surface antigens (VSA that bind female-specific antibodies induced as a result of pregnancy associated malaria (PAM. Methods Fluorescence activated cell sorting (FACS was used to measure the levels of adult Scottish and Ghanaian male, and Ghanaian pregnant female plasma immunoglobulin G (IgG that bind to the surface of infected erythrocytes. P. falciparum clone FCR3 cultures were used to assay surface IgG binding before and after selection of the parasite for adhesion to CSA. The effect of proteolytic digestion of parasite erythrocyte surface antigens on surface IgG binding and adhesion to CSA and hyaluronic acid (HA was also studied. Results P. falciparum infected erythrocytes selected for adhesion to CSA were found to express trypsin-resistant VSA that are the target of naturally acquired antibodies from pregnant women living in a malaria endemic region of Ghana. However in vitro adhesion to CSA and HA was relatively trypsin sensitive. An improved labelling technique for the detection of VSA expressed by CSA binding isolates has also been described. Conclusion The VSA expressed by CSA binding P. falciparum isolates are currently considered potential targets for a vaccine against PAM. This study identifies discordance between the trypsin sensitivity of CSA binding and surface recognition of CSA selected parasites by serum IgG from malaria exposed pregnant women. Thus, the complete molecular

  1. Neutralization and purification of thyroid stimulating antibody (TSAb) and thyroid blocking antibody (TBAb) by heterophilic antibody to animal IgG in Graves' disease.

    Science.gov (United States)

    Ochi, Yukio; Kajita, Yoshihiro; Hachiya, Takashi; Hamaoki, Masaru

    2012-01-01

    There are several reports that sera from Graves' patients contain heterophilic antibody (Ab) to animal IgG such as human anti-mouse antibody (HAMA). We examined the binding of TSAb and TBAb with heterophilic Ab. The binding of animal IgG with patient's IgG was examined by the inhibition of animal IgG on the binding of labeled bovine (b) IgG with patient's IgG. The binding to labeled bIgG was detected in the serum of 5 patients (2.7 %) among 185 patients with Graves' disease. The binding of the labeled bIgG with patient's IgG was inhibited by animal serum or the crude IgG (45% ammonium sulfate fraction of serum)(such as dog, horse, bovine, porcine, goat, ovine, rabbit, guinea-pig, rat, mouse) except human, monkey and chick. This heterophilic Ab which had cross-reaction with mammalian IgG (except human, monkey) was used as human anti-animal IgG Ab. TBII and TSAb activity of TSAb-positive serum, and TBII activity of TBAb-positive serum were neutralized by incubation with this Ab-bound column. Partial purification of TSAb- or TBAb- IgG from Protein A-purified TSAb- or TBAb-IgG was possible using this Ab-bound column. TBII and TSAb activity of TSAb-IgG and TBII activity of TBAb-IgG were neutralized by incubation with rabbit anti-human (h) IgG Ab (having cross-reaction with animal IgG). Further purification of Protein A-purified TSAb-IgG or TBAb-IgG by rabbit anti-hIgG Ab-bound column was impossible. The binding of TSAb and TBAb with heterophlic Ab means that TSAb-and TBAb-specific IgG have immunological similarity with mammalian species IgG compared to human IgG. PMID:22082836

  2. An inhibitory antibody blocks interactions between components of the malarial invasion machinery.

    Directory of Open Access Journals (Sweden)

    Christine R Collins

    2009-01-01

    Full Text Available Host cell invasion by apicomplexan pathogens such as the malaria parasite Plasmodium spp. and Toxoplasma gondii involves discharge of proteins from secretory organelles called micronemes and rhoptries. In Toxoplasma a protein complex comprising the microneme apical membrane antigen 1 (AMA1, two rhoptry neck proteins, and a protein called Ts4705, localises to the moving junction, a region of close apposition between parasite and host cell during invasion. Antibodies against AMA1 prevent invasion and are protective in vivo, and so AMA1 is of widespread interest as a malaria vaccine candidate. Here we report that the AMA1 complex identified in Toxoplasma is conserved in Plasmodium falciparum. We demonstrate that the invasion-inhibitory monoclonal antibody (mAb 4G2, which recognises P. falciparum AMA1 (PfAMA1, cannot bind when PfAMA1 is in a complex with its partner proteins. We further show that a single completely conserved PfAMA1 residue, Tyr251, lying within a conserved hydrophobic groove adjacent to the mAb 4G2 epitope, is required for complex formation. We propose that mAb 4G2 inhibits invasion by preventing PfAMA1 from interacting with other components of the invasion complex. Our findings should aid the rational design of subunit malaria vaccines based on PfAMA1.

  3. A sensitive epitope-blocking ELISA for the detection of Chikungunya virus-specific antibodies in patients.

    Science.gov (United States)

    Goh, Lucas Y H; Kam, Yiu-Wing; Metz, Stefan W; Hobson-Peters, Jody; Prow, Natalie A; McCarthy, Suzi; Smith, David W; Pijlman, Gorben P; Ng, Lisa F P; Hall, Roy A

    2015-09-15

    Chikungunya fever (CHIKF) has re-emerged as an arboviral disease that mimics clinical symptoms of other diseases such as dengue, malaria, as well as other alphavirus-related illnesses leading to problems with definitive diagnosis of the infection. Herein we describe the development and evaluation of a sensitive epitope-blocking ELISA (EB-ELISA) capable of specifically detecting anti-chikungunya virus (CHIKV) antibodies in clinical samples. The assay uses a monoclonal antibody (mAb) that binds an epitope on the E2 protein of CHIKV and does not exhibit cross-reactivity to other related alphaviruses. We also demonstrated the use of recombinant CHIK virus-like particles (VLPs) as a safe alternative antigen to infectious virions in the assay. Based on testing of 60 serum samples from patients in the acute or convalescent phase of CHIKV infection, the EB-ELISA provided us with 100% sensitivity, and exhibited 98.5% specificity when Ross River virus (RRV)- or Barmah Forest virus (BFV)-immune serum samples were included. This assay meets the public health demands of a rapid, robust, sensitive and specific, yet simple assay for specifically diagnosing CHIK-infections in humans.

  4. A Plasmodium falciparum 48/45 single epitope R0.6C subunit protein elicits high levels of transmission blocking antibodies

    DEFF Research Database (Denmark)

    Singh, Susheel K; Roeffen, Will; Andersen, Gorm;

    2015-01-01

    The sexual stage Pfs48/45 antigen is a well-established lead candidate for a transmission blocking (TB) vaccine because of its critical role in parasite fertilization. We have recently produced the carboxy-terminal 10C-fragment of Pfs48/45 containing three known epitopes for TB antibodies as a ch...

  5. A solid-phase blocking ELISA for detection of type O foot-and-mouth disease virus antibodies suitable for mass serology.

    NARCIS (Netherlands)

    Chenard, G.; Miedema, K.; Moonen, P.; Schrijver, R.S.; Dekker, A.

    2003-01-01

    A simple solid-phase blocking ELISA for the detection of antibodies directed against type O foot-and-mouth disease virus (FMDV) was developed. The ELISA was validated using field sera collected from cattle, pigs and sheep originating from FMDV infected and non-infected Dutch farms, reference sera ob

  6. Transmission-blocking antibodies against mosquito C-type lectins for dengue prevention.

    Science.gov (United States)

    Liu, Yang; Zhang, Fuchun; Liu, Jianying; Xiao, Xiaoping; Zhang, Siyin; Qin, Chengfeng; Xiang, Ye; Wang, Penghua; Cheng, Gong

    2014-02-01

    C-type lectins are a family of proteins with carbohydrate-binding activity. Several C-type lectins in mammals or arthropods are employed as receptors or attachment factors to facilitate flavivirus invasion. We previously identified a C-type lectin in Aedes aegypti, designated as mosquito galactose specific C-type lectin-1 (mosGCTL-1), facilitating the attachment of West Nile virus (WNV) on the cell membrane. Here, we first identified that 9 A. aegypti mosGCTL genes were key susceptibility factors facilitating DENV-2 infection, of which mosGCTL-3 exhibited the most significant effect. We found that mosGCTL-3 was induced in mosquito tissues with DENV-2 infection, and that the protein interacted with DENV-2 surface envelop (E) protein and virions in vitro and in vivo. In addition, the other identified mosGCTLs interacted with the DENV-2 E protein, indicating that DENV may employ multiple mosGCTLs as ligands to promote the infection of vectors. The vectorial susceptibility factors that facilitate pathogen invasion may potentially be explored as a target to disrupt the acquisition of microbes from the vertebrate host. Indeed, membrane blood feeding of antisera against mosGCTLs dramatically reduced mosquito infective ratio. Hence, the immunization against mosGCTLs is a feasible approach for preventing dengue infection. Our study provides a future avenue for developing a transmission-blocking vaccine that interrupts the life cycle of dengue virus and reduces disease burden. PMID:24550728

  7. Transmission-blocking antibodies against mosquito C-type lectins for dengue prevention.

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2014-02-01

    Full Text Available C-type lectins are a family of proteins with carbohydrate-binding activity. Several C-type lectins in mammals or arthropods are employed as receptors or attachment factors to facilitate flavivirus invasion. We previously identified a C-type lectin in Aedes aegypti, designated as mosquito galactose specific C-type lectin-1 (mosGCTL-1, facilitating the attachment of West Nile virus (WNV on the cell membrane. Here, we first identified that 9 A. aegypti mosGCTL genes were key susceptibility factors facilitating DENV-2 infection, of which mosGCTL-3 exhibited the most significant effect. We found that mosGCTL-3 was induced in mosquito tissues with DENV-2 infection, and that the protein interacted with DENV-2 surface envelop (E protein and virions in vitro and in vivo. In addition, the other identified mosGCTLs interacted with the DENV-2 E protein, indicating that DENV may employ multiple mosGCTLs as ligands to promote the infection of vectors. The vectorial susceptibility factors that facilitate pathogen invasion may potentially be explored as a target to disrupt the acquisition of microbes from the vertebrate host. Indeed, membrane blood feeding of antisera against mosGCTLs dramatically reduced mosquito infective ratio. Hence, the immunization against mosGCTLs is a feasible approach for preventing dengue infection. Our study provides a future avenue for developing a transmission-blocking vaccine that interrupts the life cycle of dengue virus and reduces disease burden.

  8. Sirolimus blocks the accumulation of hyaluronan (HA) by arterial smooth muscle cells and reduces monocyte adhesion to the ECM

    OpenAIRE

    Gouëffic, Yann; Potter-Perigo, Susan; Chan, Christina K.; Johnson, Pamela Y.; Braun, Kathleen; Evanko, Steven P.; Wight, Thomas N.

    2006-01-01

    Sirolimus (SRL), an inhibitor of human arterial smooth muscle cell (ASMC) proliferation and migration, prevents in-stent restenosis (ISR). Little is known about the effect of SRL on the extracellular matrix (ECM) component, hyaluronan, a key macromolecule in neointimal hyperplasia and inflammation. In this study, we investigated SRL regulation of the synthesis of hyaluronan by cultured human ASMC and the effect of SRL on hyaluronan mediated monocyte adhesion to the ECM. Hyaluronan production ...

  9. Characterization of inhibitory anti-insulin-like growth factor receptor antibodies with different epitope specificity and ligand-blocking properties: implications for mechanism of action in vivo.

    Science.gov (United States)

    Doern, Adam; Cao, Xianjun; Sereno, Arlene; Reyes, Christopher L; Altshuler, Angelina; Huang, Flora; Hession, Cathy; Flavier, Albert; Favis, Michael; Tran, Hon; Ailor, Eric; Levesque, Melissa; Murphy, Tracey; Berquist, Lisa; Tamraz, Susan; Snipas, Tracey; Garber, Ellen; Shestowsky, William S; Rennard, Rachel; Graff, Christilyn P; Wu, Xiufeng; Snyder, William; Cole, Lindsay; Gregson, David; Shields, Michael; Ho, Steffan N; Reff, Mitchell E; Glaser, Scott M; Dong, Jianying; Demarest, Stephen J; Hariharan, Kandasamy

    2009-04-10

    Therapeutic antibodies directed against the type 1 insulin-like growth factor receptor (IGF-1R) have recently gained significant momentum in the clinic because of preliminary data generated in human patients with cancer. These antibodies inhibit ligand-mediated activation of IGF-1R and the resulting down-stream signaling cascade. Here we generated a panel of antibodies against IGF-1R and screened them for their ability to block the binding of both IGF-1 and IGF-2 at escalating ligand concentrations (>1 microm) to investigate allosteric versus competitive blocking mechanisms. Four distinct inhibitory classes were found as follows: 1) allosteric IGF-1 blockers, 2) allosteric IGF-2 blockers, 3) allosteric IGF-1 and IGF-2 blockers, and 4) competitive IGF-1 and IGF-2 blockers. The epitopes of representative antibodies from each of these classes were mapped using a purified IGF-1R library containing 64 mutations. Most of these antibodies bound overlapping surfaces on the cysteine-rich repeat and L2 domains. One class of allosteric IGF-1 and IGF-2 blocker was identified that bound a separate epitope on the outer surface of the FnIII-1 domain. Using various biophysical techniques, we show that the dual IGF blockers inhibit ligand binding using a spectrum of mechanisms ranging from highly allosteric to purely competitive. Binding of IGF-1 or the inhibitory antibodies was associated with conformational changes in IGF-1R, linked to the ordering of dynamic or unstructured regions of the receptor. These results suggest IGF-1R uses disorder/order within its polypeptide sequence to regulate its activity. Interestingly, the activity of representative allosteric and competitive inhibitors on H322M tumor cell growth in vitro was reflective of their individual ligand-blocking properties. Many of the antibodies in the clinic likely adopt one of the inhibitory mechanisms described here, and the outcome of future clinical studies may reveal whether a particular inhibitory mechanism

  10. Development and validation of a blocking ELISA test for the detection of avian influenza antibodies in poultry species.

    Science.gov (United States)

    Henriques, Ana Margarida; Fagulha, Teresa; Barros, Sílvia Carla; Ramos, Fernanda; Duarte, Margarida; Luís, Tiago; Fevereiro, Miguel

    2016-10-01

    Avian influenza (AI) is an infectious viral disease usually asymptomatic in wild birds that can spread to domestic poultry and cause large-scale outbreaks. Some of the AI viruses (AIV) can cross the species barrier and induce fatal disease to humans, a matter of great concern worldwide. Early detection of AIV is of major importance for disease control, since prompt implementation of adequate measures can prevent spread of the virus and therefore further outbreaks. This paper reports the development and validation of a blocking ELISA using a monoclonal antibody against a conserved structural protein for the serologic diagnosis of all AI virus subtypes from domestic bird species, allowing the quick, easily automated and low-cost screening of a high number of farms. The test will be of great value not only for surveillance, but also for monitoring the efficiency of vaccination programs. Cut-off values were established in 20% of inhibition for turkey sera and in 50% of inhibition for chicken and duck sera. Estimations of 100% specificity and 100% sensitivity were obtained based on the results of known AI positive (n=130) and negative (n=208) sera, including serum samples from birds infected with other common avian viral pathogens (n=7). ROC analysis showed an area under curve (AUC) of 1.0 for chicken, duck and turkey sera, indicating that the blocking ELISA was able to perfectly discriminate between negative and positive samples of any of the poultry species tested. Inter- and intra-assay coefficients of variation were above the acceptance threshold. Furthermore, the ELISA titers were similar to the known hemagglutination inhibition titers of three positive reference sera indicating sensitivity comparable with the golden standard HI method. The method here described is an economically attractive alternative to the commercial ELISAs currently available. PMID:27421625

  11. A new approach to ELISA-based anti-glycolipid antibody evaluation of highly adhesive serum samples

    OpenAIRE

    Usuki, Seigo; O’Brien, Dawn; Rivner, Michael H.; Robert K Yu

    2014-01-01

    The enzyme-linked immunosorbent assay (ELISA) is a standard immunoassay used in measuring antibody reactivity (expressed as titers) for glycosphingolipids (GSLs) such as gangliosides and sulfoglycolipids in the sera of patients with Guillain-Barré syndrome (GBS), variants of GBS, and chronic inflammatory demyelinating polyneuropathy (CIDP). In the present study, anti-GSL antibodies were evaluated using a new formula of affinity parametric complex (APC), calculated from limiting-dilution serum...

  12. Antibodies against bovine herpesvirus (BHV) 5 may be differentiated from antibodies against BHV1 in a BHV1 glycoprotein E blocking ELISA

    NARCIS (Netherlands)

    Wellenberg, G.J.; Mars, M.H.; Oirschot, van J.T.

    2001-01-01

    We examined whether antibodies against bovine herpesvirus (BHV) 5 cross-react with BHV1 antigens and whether they could interfere with BHV1 eradication programmes. Six calves were experimentally infected with different doses of BHV5 strain N569; homologous antibodies were ?rst detectable on day 11 p

  13. Development and application of a blocking enzyme-linked immunosorbent assay (ELISA) to differentiate antibodies against live and inactivated porcine reproductive and respiratory syndrome virus.

    Science.gov (United States)

    Cong, Yanlong; Huang, Zhiqiang; Sun, Yixue; Ran, Wei; Zhu, Lisai; Yang, Guilian; Ding, Xuemei; Yang, Zhanqing; Huang, Xiao; Wang, Chunfeng; Ding, Zhuang

    2013-09-01

    The aim of this study was to establish a method that could differentiate antibodies against live and inactivated vaccines of porcine reproductive and respiratory syndrome virus (PRRSV). A blocking ELISA (b-ELISA) was established using the PRRSV non-structural protein, Nsp9, as the antigen and a monoclonal antibody, 2D6, against the Nsp9 protein as the capture antibody. The test was validated by using 415 clinical sera in the b-ELISA compared to a commercial kit based on the indirect ELISA using the nucleocapsid (N) protein as antigen. Significant differences were observed for the data obtained by the two detection methods. This may be due to the commercial kit detecting antibodies elicited by live and inactivated virus, whereas the b-ELISA only detects antibodies produced by any active viral replication, such as natural infection or live vaccination. Therefore, the b-ELISA in this study is able to distinguish between antibodies against live and inactivated viruses in pigs.

  14. Antibody fragments directed against different portions of the human neural cell adhesion molecule L1 act as inhibitors or activators of L1 function.

    Directory of Open Access Journals (Sweden)

    Yan Wang

    Full Text Available The neural cell adhesion molecule L1 plays important roles in neuronal migration and survival, neuritogenesis and synaptogenesis. L1 has also been found in tumors of different origins, with levels of L1 expression correlating positively with the metastatic potential of tumors. To select antibodies targeting the varied functions of L1, we screened the Tomlinson library of recombinant human antibody fragments to identify antibodies binding to recombinant human L1 protein comprising the entire extracellular domain of human L1. We obtained four L1 binding single-chain variable fragment antibodies (scFvs, named I4, I6, I13, and I27 and showed by enzyme-linked immunosorbent assay (ELISA that scFvs I4 and I6 have high affinity to the immunoglobulin-like (Ig domains 1-4 of L1, while scFvs I13 and I27 bind strongly to the fibronectin type III homologous (Fn domains 1-3 of L1. Application of scFvs I4 and I6 to human SK-N-SH neuroblastoma cells reduced proliferation and transmigration of these cells. Treatment of SK-N-SH cells with scFvs I13 and I27 enhanced cell proliferation and migration, neurite outgrowth, and protected against the toxic effects of H(2O(2 by increasing the ratio of Bcl-2/Bax. In addition, scFvs I4 and I6 inhibited and scFvs I13 and I27 promoted phosphorylation of src and Erk. Our findings indicate that scFvs reacting with the immunoglobulin-like domains 1-4 inhibit L1 functions, whereas scFvs interacting with the fibronectin type III domains 1-3 trigger L1 functions of cultured neuroblastoma cells.

  15. Recyclable magnetic nanocluster crosslinked with poly(ethylene oxide)-block-poly(2-vinyl-4,4-dimethylazlactone) copolymer for adsorption with antibody.

    Science.gov (United States)

    Prai-In, Yingrak; Boonthip, Chatchai; Rutnakornpituk, Boonjira; Wichai, Uthai; Montembault, Véronique; Pascual, Sagrario; Fontaine, Laurent; Rutnakornpituk, Metha

    2016-10-01

    Surface modification of magnetic nanoparticle (MNP) with poly(ethylene oxide)-block-poly(2-vinyl-4,4-dimethylazlactone) (PEO-b-PVDM) diblock copolymers and its application as recyclable magnetic nano-support for adsorption with antibody were reported herein. PEO-b-PVDM copolymers were first synthesized via a reversible addition-fragmentation chain-transfer (RAFT) polymerization using poly(ethylene oxide) chain-transfer agent as a macromolecular chain transfer agent to mediate the RAFT polymerization of VDM. They were then grafted on amino-functionalized MNP by coupling with some azlactone rings of the PVDM block to form magnetic nanoclusters with tunable cluster size. The nanocluster size could be tuned by adjusting the chain length of the PVDM block. The nanoclusters were successfully used as efficient and recyclable nano-supports for adsorption with anti-rabbit IgG antibody. They retained higher than 95% adsorption of the antibody during eight adsorption-separation-desorption cycles, indicating the potential feasibility in using this novel hybrid nanocluster as recyclable support in cell separation applications. PMID:27287124

  16. Population diversity and antibody selective pressure to Plasmodium falciparum MSP1 block2 locus in an African malaria-endemic setting

    Directory of Open Access Journals (Sweden)

    Trape Jean-François

    2009-10-01

    Full Text Available Abstract Background Genetic evidence for diversifying selection identified the Merozoite Surface Protein1 block2 (PfMSP1 block2 as a putative target of protective immunity against Plasmodium falciparum. The locus displays three family types and one recombinant type, each with multiple allelic forms differing by single nucleotide polymorphism as well as sequence, copy number and arrangement variation of three amino acid repeats. The family-specific antibody responses observed in endemic settings support immune selection operating at the family level. However, the factors contributing to the large intra-family allelic diversity remain unclear. To address this question, population allelic polymorphism and sequence variant-specific antibody responses were studied in a single Senegalese rural community where malaria transmission is intense and perennial. Results Family distribution showed no significant temporal fluctuation over the 10 y period surveyed. Sequencing of 358 PCR fragments identified 126 distinct alleles, including numerous novel alleles in each family and multiple novel alleles of recombinant types. The parasite population consisted in a large number of low frequency alleles, alongside one high-frequency and three intermediate frequency alleles. Population diversity tests supported positive selection at the family level, but showed no significant departure from neutrality when considering intra-family allelic sequence diversity and all families combined. Seroprevalence, analysed using biotinylated peptides displaying numerous sequence variants, was moderate and increased with age. Reactivity profiles were individual-specific, mapped to the family-specific flanking regions and to repeat sequences shared by numerous allelic forms within a family type. Seroreactivity to K1-, Mad20- and R033 families correlated with the relative family genotype distribution within the village. Antibody specificity remained unchanged with cumulated exposure

  17. Development and evaluation of a blocking enzyme-linked immunosorbent assay and virus neutralization assay to detect antibodies to viral hemorrhagic septicemia virus

    Science.gov (United States)

    Wilson, Anna; Goldberg, Tony; Marcquenski, Susan; Olson, Wendy; Goetz, Frederick; Hershberger, Paul; Hart, Lucas M.; Toohey-Kurth, Kathy

    2014-01-01

    Viral hemorrhagic septicemia virus (VHSV) is a target of surveillance by many state and federal agencies in the United States. Currently, the detection of VHSV relies on virus isolation, which is lethal to fish and indicates only the current infection status. A serological method is required to ascertain prior exposure. Here, we report two serologic tests for VHSV that are nonlethal, rapid, and species independent, a virus neutralization (VN) assay and a blocking enzyme-linked immunosorbent assay (ELISA). The results show that the VN assay had a specificity of 100% and sensitivity of 42.9%; the anti-nucleocapsid-blocking ELISA detected nonneutralizing VHSV antibodies at a specificity of 88.2% and a sensitivity of 96.4%. The VN assay and ELISA are valuable tools for assessing exposure to VHSV.

  18. Inhibitory Monoclonal Antibodies against Mouse Proteases Raised in Gene-Deficient Mice Block Proteolytic Functions in vivo

    DEFF Research Database (Denmark)

    Lund, Ida K; Rasch, Morten G; Ingvarsen, Signe;

    2012-01-01

    Identification of targets for cancer therapy requires the understanding of the in vivo roles of proteins, which can be derived from studies using gene-targeted mice. An alternative strategy is the administration of inhibitory monoclonal antibodies (mAbs), causing acute disruption of the target pr...

  19. Detection of antibodies to Actinobacillus pleuropneumoniae serotype 12 in pig serum using a blocking enzyme-linked immunosorbent assay

    DEFF Research Database (Denmark)

    Andresen, Lars Ole; Klausen, Joan; Barfod, Kristen;

    2002-01-01

    in samples of pig serum were detected by inhibition of the binding of polyclonal rabbit antibodies raised against Ap serotype 12. The assay was evaluated against sera from experimentally infected pigs, from pig herds naturally infected with Ap and from herds declared free of Ap serotypc 12 infection...

  20. Anti-α4 antibody treatment blocks virus traffic to the brain and gut early, and stabilizes CNS injury late in infection.

    Directory of Open Access Journals (Sweden)

    Jennifer H Campbell

    2014-12-01

    Full Text Available Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab once a week for three weeks beginning on 28 days post-infection (late. Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS, and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+ in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.

  1. In vitro evaluation of poly(ethylene glycol)-block-poly(ɛ-caprolactone) methyl ether copolymer coating effects on cells adhesion and proliferation

    Science.gov (United States)

    Rusen, Laurentiu; Neacsu, Patricia; Cimpean, Anisoara; Valentin, Ion; Brajnicov, Simona; Dumitrescu, L. N.; Banita, Janina; Dinca, Valentina; Dinescu, Maria

    2016-06-01

    Understanding and controlling natural and synthetic biointerfaces is known to be the key to a wide variety of application within cell culture and tissue engineering field. As both material characteristics and methods are important in tailoring biointerfaces characteristics, in this work we explore the feasibility of using Matrix Assisted Pulsed Laser Evaporation technique for obtaining synthetic copolymeric biocoatings (i.e. poly(ethylene glycol)-block-poly(ɛ-caprolactone) methyl ether) for evaluating in vitro Vero and MC3T3-E1 pre-osteoblasts cell response. Characterization and evaluation of the coated substrates were carried out using different techniques. The Fourier transform infrared spectroscopy data demonstrated that the main functional groups in the MAPLE-deposited films remained intact. Atomic Force Microscopy images showed the coatings to be continuous, with the surface roughness depending on the deposition parameters. Moreover, the behaviour of the coatings in medium mimicking the pH and temperature of the human body was studied and corelated to degradation. Spectro-ellipsometry (SE) and AFM measurements revealed the degradation trend during immersion time by the changes in coating thickness and roughness. In vitro biocompatibility was studied by indirect contact tests on Vero cells in accordance with ISO 10993-5/2009. The results obtained in terms of cell morphology (phase contrast microscopy) and cytotoxicity (LDH and MTT assays) proved biocompatibility. Furthermore, direct contact assays on MC3T3-E1 pre-osteoblasts demonstrated the capacity of all analyzed specimens to support cell adhesion, normal cellular morphology and growth.

  2. Functionalization of Block Copolymer Vesicle Surfaces

    Directory of Open Access Journals (Sweden)

    Wolfgang Meier

    2011-01-01

    Full Text Available In dilute aqueous solutions certain amphiphilic block copolymers self-assemble into vesicles that enclose a small pool of water with a membrane. Such polymersomes have promising applications ranging from targeted drug-delivery devices, to biosensors, and nanoreactors. Interactions between block copolymer membranes and their surroundings are important factors that determine their potential biomedical applications. Such interactions are influenced predominantly by the membrane surface. We review methods to functionalize block copolymer vesicle surfaces by chemical means with ligands such as antibodies, adhesion moieties, enzymes, carbohydrates and fluorophores. Furthermore, surface-functionalization can be achieved by self-assembly of polymers that carry ligands at their chain ends or in their hydrophilic blocks. While this review focuses on the strategies to functionalize vesicle surfaces, the applications realized by, and envisioned for, such functional polymersomes are also highlighted.

  3. A liquid-phase-blocking concanavalin A enzyme-linked immunosorbent assay for the detection of antibodies against Newcastle disease virus in serum of free-ranging pigeons.

    Science.gov (United States)

    de Oliveira, Elisabete Schirato; Silva, Ketherson Rodrigues; Fernando, Filipe Santos; Gonçalves, Mariana Costa Mello; Fernandes, Camila Cesário; Borzi, Mariana Monezi; dos Santos, Romeu Moreira; Tamanini, Maria de Lourdes Feres; Montassier, Maria de Fátima da Silva; Montassier, Helio José

    2013-11-01

    A competitive liquid-phase-blocking concanavalin A enzyme-linked immunosorbent assay (LPB-ConA-ELISA) was developed in the current study. The assay used ConA as a capture reagent, and the sera of specific pathogen-free chickens immunized with nonpurified Newcastle disease virus (NDV) suspension as detector antibodies, to detect and quantify specific antiviral antibodies in serum samples from free-ranging pigeons. The comparison between the LPB-ConA-ELISA and the hemagglutination inhibition (HI) test for the detection of antibodies in serum samples from 107 pigeons showed significant correlation between the assays (r = 0.875), a high sensitivity (100%), specificity (95.8%), accuracy (96.3%) for the ELISA, and good agreement (κ = 0.83) between the 2 assays. The results of this study suggest that the LPB-ConA-ELISA could be a useful alternative to HI test in the serodiagnosis of NDV in pigeons, or other species of birds.

  4. Role of adhesion molecules and dendritic cells in rat hepatic/renal ischemia-reperfusion injury and anti-adhesive intervention with anti-P-selectin lectin-EGF domain monoclonal antibody

    Institute of Scientific and Technical Information of China (English)

    Tong Zhou; Gui-Zhi Sun; Ming-Jun Zhang; Jin-Lian Chen; Dong-Qing Zhang; Qing-Shen Hu; Yu-Ying Chen; Nan Chen

    2005-01-01

    AIM: To investigate the role of P-selectin, intercellular adhesion molecule-1 (ICAM-1) and dendritic cells (DCs)in liver/kidney of rats with hepatic/renal ischemiareperfusion injury and the preventive effect of anti-Pselectin lectin-EGF domain monoclonal antibody (anti-PsLEGFmAb) on the injury.METHODS: Rat models of hepatic and renal ischemiareperfusion were established. The rats were then divided into two groups, one group treated with anti-PsL-EGFmAb(n = 20) and control treated with saline (n = 20). Both groups were subdivided into four groups according to reperfusion time (1, 3, 6 and 24 h). The sham-operated group (n = 5) served as a control group. DCs were observed by the microscopic image method, while P-selectin and ICAM-1 were analyzed by immunohistochemistry.RESULTS: P-selectin increased significantly in hepatic sinusoidal endothelial cells and renal tubular epithelial cells 1 h after ischemia-reperfusion, and the expression of ICAM-1 was up-regulated in hepatic sinusoid and renal vessels after 6 h. CD1a+CD80+DCs gradually increased in hepatic sinusoidal endothelium and renal tubules and interstitium 1 h after ischemia-reperfusion, and there was the most number of DCs in 24-h group. The localization of DCs was associated with rat hepatic/renal function.These changes became less significant in rats treated with anti-PsL-EGFmAb.CONCLUSION: DCs play an important role in immune pathogenesis of hepatic/renal ischemia-reperfusion injury.Anti-PsL-EGFmAb may regulate and inhibit local DC immigration and accumulation in liver/kidney.

  5. Identification of an erythrocyte binding peptide from the erythrocyte binding antigen, EBA-175, which blocks parasite multiplication and induces peptide-blocking antibodies

    DEFF Research Database (Denmark)

    Jakobsen, P H; Heegaard, P M; Koch, C;

    1998-01-01

    A biotinylated peptide covering a sequence of 21 amino acids (aa) from the erythrocyte binding antigen (EBA-175) of Plasmodium falciparum bound to human glycophorin A, an erythrocyte receptor for merozoites, as demonstrated by enzyme-linked immunosorbent assay (ELISA) and to erythrocytes as demon......A biotinylated peptide covering a sequence of 21 amino acids (aa) from the erythrocyte binding antigen (EBA-175) of Plasmodium falciparum bound to human glycophorin A, an erythrocyte receptor for merozoites, as demonstrated by enzyme-linked immunosorbent assay (ELISA) and to erythrocytes...... as demonstrated by flow cytometry analysis. The peptide, EBA(aa1076-96), also bound to desialylated glycophorin A and glycophorin B when tested by ELISA. The peptide blocked parasite multiplication in vitro. The glycophorin A binding sequence was further delineated to a 12-aa sequence, EBA(aa1085-96), by testing...... the binding of a range of truncated peptides to immobilized glycophorin A. Our data indicate that EBA(aa1085-96) is part of a ligand on the merozoite for binding to erythrocyte receptors. This binding suggests that the EBA(aa1085-96) peptide is involved in a second binding step, independent of sialic acid...

  6. Identification of an erythrocyte binding peptide from the erythrocyte binding antigen, EBA-175, which blocks parasite multiplication and induces peptide-blocking antibodies

    DEFF Research Database (Denmark)

    Jakobsen, P.H.; Heegaard, Peter M. H.; Koch, C.;

    1998-01-01

    A biotinylated peptide covering a sequence of 21 amino acids (aa) from the erythrocyte binding antigen (EBA-175) of Plasmodium falciparum bound to human glycophorin A, an erythrocyte receptor for merozoites, as demonstrated by enzyme-linked immunosorbent assay (ELISA) and to erythrocytes as demon......A biotinylated peptide covering a sequence of 21 amino acids (aa) from the erythrocyte binding antigen (EBA-175) of Plasmodium falciparum bound to human glycophorin A, an erythrocyte receptor for merozoites, as demonstrated by enzyme-linked immunosorbent assay (ELISA) and to erythrocytes...... as demonstrated by flow cytometry analysis. The peptide, EBA(aa1076-96), also bound to desialylated glycophorin A and glycophorin B when tested by ELISA, The peptide blocked parasite multiplication in vitro. The glycophorin A binding sequence was further delineated to a 12-aa sequence, EBA(aa1085-96), by testing...... the binding of a range of truncated peptides to immobilized glycophorin A. Our data indicate that EBA(aa1085-96) is part of a ligand on the merozoite for binding to erythrocyte receptors. This binding suggests that the EBA(aa1085-96) peptide is involved in a second binding step, independent of sialic acid...

  7. Blocking enzyme-linked immunosorbent assay for detection of antibodies against Actinobacillus pleuropneumoniae serotype 6 in pig serum

    DEFF Research Database (Denmark)

    Klausen, Joan; Andresen, Lars Ole; Barfod, Kristen;

    2001-01-01

    was used as antigen. The blocking ELISA was tested against sera from pigs experimentally infected with the 12 serotypes of Ap biotype 1. Cross-reaction with serotypes 3 and 8 but not with other serotypes was observed. The sensitivity and specificity of the test on a herd level were evaluated with sera from...

  8. Single chain variable fragment antibodies block aggregation and toxicity induced by familial ALS-linked mutant forms of SOD1

    Science.gov (United States)

    Ghadge, Ghanashyam D.; Pavlovic, John; Koduvayur, Sujatha P.; Kay, Brian K.; Roos, Raymond P.

    2013-01-01

    Approximately 10% of amyotrophic lateral sclerosis (ALS) cases are familial (known as FALS) with an autosomal dominant inheritance pattern, and ~25% of FALS cases are caused by mutations in Cu/Zn superoxide dismutase (SOD1). There is convincing evidence that mutant SOD1 (mtSOD1) kills motor neurons (MNs) because of a gain-of-function toxicity, most likely related to aggregation of mtSOD1. A number of recent reports have suggested that antibodies can be used to treat mtSOD1-induced FALS. To follow up on the use of antibodies as potential therapeutics, we generated single chain fragments of variable region antibodies (scFvs) against SOD1, and then expressed them as ‘intrabodies’ within a motor neuron cell line. In the present study, we describe isolation of human scFvs that interfere with mtSOD1 in vitro aggregation and toxicity. These scFvs may have therapeutic potential in sporadic ALS, as well as FALS, given that sporadic ALS may also involve abnormalities in the SOD1 protein or activity. PMID:23607939

  9. Fluorescence Adherence Inhibition Assay: A Novel Functional Assessment of Blocking Virus Attachment by Vaccine-Induced Antibodies.

    Directory of Open Access Journals (Sweden)

    Atul Asati

    Full Text Available Neutralizing antibodies induced by vaccination or natural infection play a critically important role in protection against the viral diseases. In general, neutralization of the viral infection occurs via two major pathways: pre- and post-attachment modes, the first being the most important for such infections as influenza and polio, the latter being significant for filoviruses. Neutralizing capacity of antibodies is typically evaluated by virus neutralization assays that assess reduction of viral infectivity to the target cells in the presence of functional antibodies. Plaque reduction neutralization test, microneutralization and immunofluorescent assays are often used as gold standard virus neutralization assays. However, these methods are associated with several important prerequisites such as use of live virus requiring safety precautions, tedious evaluation procedure and long assessment time. Hence, there is a need for a robust, inexpensive high throughput functional assay that can be performed rapidly using inactivated virus, without extensive safety precautions. Herein, we report a novel high throughput Fluorescence Adherence Inhibition assay (fADI using inactivated virus labeled with fluorescent secondary antibodies virus and Vero cells or erythrocytes as targets. It requires only few hours to assess pre-attachment neutralizing capacity of donor sera. fADI assay was tested successfully on donors immunized with polio, yellow fever and influenza vaccines. To further simplify and improve the throughput of the assay, we have developed a mathematical approach for calculating the 50% titers from a single sample dilution, without the need to analyze multi-point titration curves. Assessment of pre- and post-vaccination human sera from subjects immunized with IPOL®, YF-VAX® and 2013-2014 Fluzone® vaccines demonstrated high efficiency of the assay. The results correlated very well with microneutralization assay performed independently by the FDA

  10. Fluorescence Adherence Inhibition Assay: A Novel Functional Assessment of Blocking Virus Attachment by Vaccine-Induced Antibodies.

    Science.gov (United States)

    Asati, Atul; Kachurina, Olga; Karol, Alex; Dhir, Vipra; Nguyen, Michael; Parkhill, Robert; Kouiavskaia, Diana; Chumakov, Konstantin; Warren, William; Kachurin, Anatoly

    2016-01-01

    Neutralizing antibodies induced by vaccination or natural infection play a critically important role in protection against the viral diseases. In general, neutralization of the viral infection occurs via two major pathways: pre- and post-attachment modes, the first being the most important for such infections as influenza and polio, the latter being significant for filoviruses. Neutralizing capacity of antibodies is typically evaluated by virus neutralization assays that assess reduction of viral infectivity to the target cells in the presence of functional antibodies. Plaque reduction neutralization test, microneutralization and immunofluorescent assays are often used as gold standard virus neutralization assays. However, these methods are associated with several important prerequisites such as use of live virus requiring safety precautions, tedious evaluation procedure and long assessment time. Hence, there is a need for a robust, inexpensive high throughput functional assay that can be performed rapidly using inactivated virus, without extensive safety precautions. Herein, we report a novel high throughput Fluorescence Adherence Inhibition assay (fADI) using inactivated virus labeled with fluorescent secondary antibodies virus and Vero cells or erythrocytes as targets. It requires only few hours to assess pre-attachment neutralizing capacity of donor sera. fADI assay was tested successfully on donors immunized with polio, yellow fever and influenza vaccines. To further simplify and improve the throughput of the assay, we have developed a mathematical approach for calculating the 50% titers from a single sample dilution, without the need to analyze multi-point titration curves. Assessment of pre- and post-vaccination human sera from subjects immunized with IPOL®, YF-VAX® and 2013-2014 Fluzone® vaccines demonstrated high efficiency of the assay. The results correlated very well with microneutralization assay performed independently by the FDA Center of

  11. Fluorescence Adherence Inhibition Assay: A Novel Functional Assessment of Blocking Virus Attachment by Vaccine-Induced Antibodies.

    Science.gov (United States)

    Asati, Atul; Kachurina, Olga; Karol, Alex; Dhir, Vipra; Nguyen, Michael; Parkhill, Robert; Kouiavskaia, Diana; Chumakov, Konstantin; Warren, William; Kachurin, Anatoly

    2016-01-01

    Neutralizing antibodies induced by vaccination or natural infection play a critically important role in protection against the viral diseases. In general, neutralization of the viral infection occurs via two major pathways: pre- and post-attachment modes, the first being the most important for such infections as influenza and polio, the latter being significant for filoviruses. Neutralizing capacity of antibodies is typically evaluated by virus neutralization assays that assess reduction of viral infectivity to the target cells in the presence of functional antibodies. Plaque reduction neutralization test, microneutralization and immunofluorescent assays are often used as gold standard virus neutralization assays. However, these methods are associated with several important prerequisites such as use of live virus requiring safety precautions, tedious evaluation procedure and long assessment time. Hence, there is a need for a robust, inexpensive high throughput functional assay that can be performed rapidly using inactivated virus, without extensive safety precautions. Herein, we report a novel high throughput Fluorescence Adherence Inhibition assay (fADI) using inactivated virus labeled with fluorescent secondary antibodies virus and Vero cells or erythrocytes as targets. It requires only few hours to assess pre-attachment neutralizing capacity of donor sera. fADI assay was tested successfully on donors immunized with polio, yellow fever and influenza vaccines. To further simplify and improve the throughput of the assay, we have developed a mathematical approach for calculating the 50% titers from a single sample dilution, without the need to analyze multi-point titration curves. Assessment of pre- and post-vaccination human sera from subjects immunized with IPOL®, YF-VAX® and 2013-2014 Fluzone® vaccines demonstrated high efficiency of the assay. The results correlated very well with microneutralization assay performed independently by the FDA Center of

  12. Expression profile of vascular cell adhesion molecule-1 (CD106) in inflammatory foci using rhenium-188 labelled monoclonal antibody in mice.

    Science.gov (United States)

    Kairemo, K J; Strömberg, S; Nikula, T K; Karonen, S L

    1998-06-01

    Rhenium (Re)-188 is a generator (W-188/Re-188) produced high energy beta-emitter suitable for radionuclide therapy (T1/2 is 16.9 hrs and Emax 2.1 MeV (range 11 mm)). We have labelled monoclonal antibody (MAb) raised against vascular cell adhesion molecule-1 (VCAM-1) with Re-188 using glucoheptonate chelation technique and SnCl2 as reducing agent. The labelling efficiency, free perrhenate and reduced Re were controlled with thin layer chromatography and the purification of Re-188-MoAbs was performed using gel filtration. Our results indicate that Re-188-labelled antibodies remain in vitro stable and the labelling purity is > 90%. We also have applied these Re-188-MoAbs for detection of inflammatory disease in a mouse. The effective half-lives of organs of interest after an injection of Re-188-anti-VCAM1 were as follows: blood 5.2 hr, kidney 4.7 hr, and liver 9.6 hr. Re-188-anti-VCAM-1 was found to accumulate mainly in kidney and liver. One hour after the injection, the kidney contained in average as high as 12.5% and the liver 2.8 ID/g tissue. After 6 hr, the kidney contained 5.5% ID/g and the liver 2.6% ID/g. At 24 hr, the kidney uptake was 0.5% ID/g and the liver uptake 0.8% ID/g, respectively. The inflamed foci, subcutaneous lesions in the footpad skin, were visualized using gamma camera. From the distribution data the uptakes in the inflamed foci as follows: at 1 hr 2.18 (inflammation) and 1.72% ID/g (control), at 6 hr 1.42 (inflammation) and 0.85% ID/g (control), and at 24 hr 0.17 (inflammation) and 0.084% ID/g (control), respectively. Anti-VCAM-1 MAb showed better targeting as compared to control MoAbs in inflammation (caused by E.coli lipoplysaccaride). In conclusion, Re-188 is suitable for MAb labelling, and MAb against VCAM-1 may be used for detection of local inflammatory disease. PMID:9762472

  13. A novel anti-EMMPRIN function-blocking antibody reduces T cell proliferation and neurotoxicity: relevance to multiple sclerosis

    OpenAIRE

    Agrawal Smriti M; Silva Claudia; Wang Janet; Tong Jade; Yong V

    2012-01-01

    Abstract Background Extracellular matrix metalloproteinase inducer (EMMPRIN; CD147, basigin) is an inducer of the expression of several matrix metalloproteinases (MMPs). We reported previously that blocking EMMPRIN activity reduced neuroinflammation and severity of disease in an animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). Methods To improve upon EMMPRIN blockade, and to help unravel the biological functions of EMMPRIN in inflammatory disorders, we...

  14. Multibody simulation of adhesion pili

    CERN Document Server

    Zakrisson, Johan; Servin, Martin; Axner, Ove; Lacoursiere, Claude; Andersson, Magnus

    2014-01-01

    We present a coarse grained rigid multibody model of a subunit assembled helix-like polymer, e.g., adhesion pili expressed by bacteria, that is capable of describing the polymers force-extension response. With building blocks representing individual subunits the model appropriately describes the complex behavior of pili expressed by the gram-negative uropathogenic Escherichia coli bacteria under the action of an external force. Numerical simulations show that the dynamics of the model, which include both the effects of unwinding and rewinding, are in good quantitative agreement with the characteristic force-extension response as observed experimentally for type 1 and P pili. By tuning the model, it is also possible to reproduce the force-extension response in the presence of anti-shaft antibodies, which dramatically changes the mechanical properties. Thus, the model and the results in this work give enhanced understanding of how a pilus unwinds under action of external forces and provide new perspective of th...

  15. Antibody against recombinant heat labile enterotoxin B subunit (rLTB could block LT binding to ganglioside M1 receptor

    Directory of Open Access Journals (Sweden)

    SM Moazzeni

    2010-12-01

    Full Text Available Objectives: Enterotoxigenic Escherichia coli (ETEC is one of the most common agents of diarrhea among other bacterial agents. Designing and producing vaccine against these bacteria is one of the major purposes of World Health Organization (WHO. Due to presence of diverse clones of ETEC strains in the world, the use of global vaccines for ETEC infection is controversial. B subunit of heat labile toxin (LTB was introduced as a vaccine candidate molecule by several investigators. The expression of LTB gene isolated from a local bacterial strain and investigation of its immunological property was the objective of this study."nMaterials and Methods: LTB gene was isolated from a local isolated ETEC, cloned and expressed using pET28a expression vector. For LTB gene expression, the three main expression parameters (IPTG concentration, time and temperature of induction were investigated. The recombinant protein was purified ( > 95% with Ni-NTA column using 6XHis-tag and used as an antigen in ELISA test."nResults: The immunological analyses showed production of high titer of specific antibody in immunized mice. Anti LTB Antibody could bind to whole toxin and neutralize the toxin through inhibition of its binding to the Ganglioside M1 receptor."nConclusion: The recombinant LTB protein is a highly immunogenic molecule. Considering the LTB role in ETEC pathogenesis, it can be taken into account as one of the most important components of vaccines against local ETEC.

  16. A plant-produced Pfs25 VLP malaria vaccine candidate induces persistent transmission blocking antibodies against Plasmodium falciparum in immunized mice.

    Science.gov (United States)

    Jones, R Mark; Chichester, Jessica A; Mett, Vadim; Jaje, Jennifer; Tottey, Stephen; Manceva, Slobodanka; Casta, Louis J; Gibbs, Sandra K; Musiychuk, Konstantin; Shamloul, Moneim; Norikane, Joey; Mett, Valentina; Streatfield, Stephen J; van de Vegte-Bolmer, Marga; Roeffen, Will; Sauerwein, Robert W; Yusibov, Vidadi

    2013-01-01

    Malaria transmission blocking vaccines (TBVs) are considered an effective means to control and eventually eliminate malaria. The Pfs25 protein, expressed predominantly on the surface of the sexual and sporogonic stages of Plasmodium falciparum including gametes, zygotes and ookinetes, is one of the primary targets for TBV. It has been demonstrated that plants are an effective, highly scalable system for the production of recombinant proteins, including virus-like particles (VLPs). We engineered VLPs (Pfs25-CP VLP) comprising Pfs25 fused to the Alfalfa mosaic virus coat protein (CP) and produced these non-enveloped hybrid VLPs in Nicotiana benthamiana plants using a Tobacco mosaic virus-based 'launch' vector. Purified Pfs25-CP VLPs were highly consistent in size (19.3±2.4 nm in diameter) with an estimated 20-30% incorporation of Pfs25 onto the VLP surface. Immunization of mice with one or two doses of Pfs25-CP VLPs plus Alhydrogel® induced serum antibodies with complete transmission blocking activity through the 6 month study period. These results support the evaluation of Pfs25-CP VLP as a potential TBV candidate and the feasibility of the 'launch' vector technology for the production of VLP-based recombinant vaccines against infectious diseases. PMID:24260245

  17. A plant-produced Pfs25 VLP malaria vaccine candidate induces persistent transmission blocking antibodies against Plasmodium falciparum in immunized mice.

    Directory of Open Access Journals (Sweden)

    R Mark Jones

    Full Text Available Malaria transmission blocking vaccines (TBVs are considered an effective means to control and eventually eliminate malaria. The Pfs25 protein, expressed predominantly on the surface of the sexual and sporogonic stages of Plasmodium falciparum including gametes, zygotes and ookinetes, is one of the primary targets for TBV. It has been demonstrated that plants are an effective, highly scalable system for the production of recombinant proteins, including virus-like particles (VLPs. We engineered VLPs (Pfs25-CP VLP comprising Pfs25 fused to the Alfalfa mosaic virus coat protein (CP and produced these non-enveloped hybrid VLPs in Nicotiana benthamiana plants using a Tobacco mosaic virus-based 'launch' vector. Purified Pfs25-CP VLPs were highly consistent in size (19.3±2.4 nm in diameter with an estimated 20-30% incorporation of Pfs25 onto the VLP surface. Immunization of mice with one or two doses of Pfs25-CP VLPs plus Alhydrogel® induced serum antibodies with complete transmission blocking activity through the 6 month study period. These results support the evaluation of Pfs25-CP VLP as a potential TBV candidate and the feasibility of the 'launch' vector technology for the production of VLP-based recombinant vaccines against infectious diseases.

  18. Targeted suppression of autoreactive CD8+ T-cell activation using blocking anti-CD8 antibodies

    Science.gov (United States)

    Clement, Mathew; Pearson, James A.; Gras, Stephanie; van den Berg, Hugo A.; Lissina, Anya; Llewellyn-Lacey, Sian; Willis, Mark D.; Dockree, Tamsin; McLaren, James E.; Ekeruche-Makinde, Julia; Gostick, Emma; Robertson, Neil P.; Rossjohn, Jamie; Burrows, Scott R.; Price, David A.; Wong, F. Susan; Peakman, Mark; Skowera, Ania; Wooldridge, Linda

    2016-01-01

    CD8+ T-cells play a role in the pathogenesis of autoimmune diseases such as multiple sclerosis and type 1 diabetes. However, drugs that target the entire CD8+ T-cell population are not desirable because the associated lack of specificity can lead to unwanted consequences, most notably an enhanced susceptibility to infection. Here, we show that autoreactive CD8+ T-cells are highly dependent on CD8 for ligand-induced activation via the T-cell receptor (TCR). In contrast, pathogen-specific CD8+ T-cells are relatively CD8-independent. These generic differences relate to an intrinsic dichotomy that segregates self-derived and exogenous antigen-specific TCRs according to the monomeric interaction affinity with cognate peptide-major histocompatibility complex class I (pMHCI). As a consequence, “blocking” anti-CD8 antibodies can suppress autoreactive CD8+ T-cell activation in a relatively selective manner. These findings provide a rational basis for the development and in vivo assessment of novel therapeutic strategies that preferentially target disease-relevant autoimmune responses within the CD8+ T-cell compartment. PMID:27748447

  19. Abdominal Adhesions

    Science.gov (United States)

    ... adhesions? Abdominal adhesions can cause intestinal obstruction and female infertility—the inability to become pregnant after a year of trying. Abdominal adhesions can lead to female infertility by preventing fertilized eggs from reaching the uterus, ...

  20. Antibodies Directed against Shiga-Toxin Producing Escherichia coli Serotype O103 Type III Secreted Proteins Block Adherence of Heterologous STEC Serotypes to HEp-2 Cells.

    Directory of Open Access Journals (Sweden)

    Taseen S Desin

    Full Text Available Shiga toxin-producing Escherichia coli (STEC serotype O103 is a zoonotic pathogen that is capable of causing hemorrhagic colitis and hemolytic uremic syndrome (HUS in humans. The main animal reservoir for STEC is ruminants and hence reducing the levels of this pathogen in cattle could ultimately lower the risk of STEC infection in humans. During the process of infection, STECO103 uses a Type III Secretion System (T3SS to secrete effector proteins (T3SPs that result in the formation of attaching and effacing (A/E lesions. Vaccination of cattle with STEC serotype O157 T3SPs has previously been shown to be effective in reducing shedding of STECO157 in a serotype-specific manner. In this study, we tested the ability of rabbit polyclonal sera against individual STECO103 T3SPs to block adherence of the organism to HEp-2 cells. Our results demonstrate that pooled sera against EspA, EspB, EspF, NleA and Tir significantly lowered the adherence of STECO103 relative to pre-immune sera. Likewise, pooled anti-STECO103 sera were also able to block adherence by STECO157. Vaccination of mice with STECO103 recombinant proteins induced strong IgG antibody responses against EspA, EspB, NleA and Tir but not against EspF. However, the vaccine did not affect fecal shedding of STECO103 compared to the PBS vaccinated group over the duration of the experiment. Cross reactivity studies using sera against STECO103 recombinant proteins revealed a high degree of cross reactivity with STECO26 and STECO111 proteins implying that sera against STECO103 proteins could potentially provide neutralization of attachment to epithelial cells by heterologous STEC serotypes.

  1. The epitope of monoclonal antibodies blocking erythrocyte invasion by Plasmodium falciparum map to the dimerization and receptor glycan binding sites of EBA-175.

    Directory of Open Access Journals (Sweden)

    Xavier Ambroggio

    Full Text Available The malaria parasite, Plasmodium falciparum, and related parasites use a variety of proteins with Duffy-Binding Like (DBL domains to bind glycoproteins on the surface of host cells. Among these proteins, the 175 kDa erythrocyte binding antigen, EBA-175, specifically binds to glycophorin A on the surface of human erythrocytes during the process of merozoite invasion. The domain responsible for glycophorin A binding was identified as region II (RII which contains two DBL domains, F1 and F2. The crystal structure of this region revealed a dimer that is presumed to represent the glycophorin A binding conformation as sialic acid binding sites and large cavities are observed at the dimer interface. The dimer interface is largely composed of two loops from within each monomer, identified as the F1 and F2 β-fingers that contact depressions in the opposing monomers in a similar manner. Previous studies have identified a panel of five monoclonal antibodies (mAbs termed R215 to R218 and R256 that bind to RII and inhibit invasion of erythrocytes to varying extents. In this study, we predict the F2 β-finger region as the conformational epitope for mAbs, R215, R217, and R256, and confirm binding for the most effective blocking mAb R217 and R215 to a synthetic peptide mimic of the F2 β-finger. Localization of the epitope to the dimerization and glycan binding sites of EBA-175 RII and site-directed mutagenesis within the predicted epitope are consistent with R215 and R217 blocking erythrocyte invasion by Plasmodium falciparum by preventing formation of the EBA-175- glycophorin A complex.

  2. Signaling transduction pathways involved in basophil adhesion and histamine release

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Background Little is known about basophil with respect to the different signaling transduction pathways involved in spontaneous, cytokine or anti-IgE induced adhesion and how this compares to IgE-dependent and IgE-independent mediator secretion. The purpose of the present study was to investigate the roles of β1 andβ2 integrins in basophil adhesion as well as hosphatidylinositol 3-kinase (PI3K), src-kinases and extracellular signal regulated kinase (ERK)1/2 in basophil adhesion and histamine release (HR). Methods Basophils (purity of 10%-50%) were preincubated with anti-CD29 or anti-CD18 blocking antibodies before used for adhesion study. Basophils were preincubated with the pharmacological inhibitors wortmannin, PP1, PD98059 before used for adhesion and HR study. Cell adherence to bovine serum albumin (BSA) or fibronectin (Fn) was monitored using cell associated histamine as a basophil marker and the histamine was measured by the glass fiber assay.Results Basophil spontaneous adhesion to Fn was inhibited by anti-CD29. Interleukin (IL)-3, granulocyte/macrophage colony stimulating factor (GM-CSF) induced adhesion to BSA was inhibited by anti-CD18. Wortmannin at 1 μmol/L and PP1 at 20 μmol/L strongly interfered with, whereas PD98059 at 50 μmol/L weakly inhibited basophil spontaneous adhesion to Fn. One μmol/L wortmannin strongly inhibited IL-3, IL-5, GM-CSF and anti-IgE induced adhesion to BSA. PP1 at 20 μmol/L partly inhibited anti-IgE induced adhesion. Fifty μmol/L PD98059 marginally inhibited IL-5, weakly inhibited anti-IgE, partly inhibited GM-CSF induced adhesion. Wortmannin, PP1 and PD98059 inhibited anti-IgE (1:100 or 1:1000) induced basophil HR in a dose dependent manner. They inhibited calcium ionophore A23187 (10 μmol/L, 5 μmol/L) induced basophil HR in a dose dependent manner, but to different extend with PP1 being the most efficient.Conclusions Basophil spontaneous adhesion to Fn is mediated by β1-integrins whereas cytokine induced adhesion

  3. Anti-La (SS-B) but not anti-Ro52 (SS-A) antibodies cross-react with laminin--a role in the pathogenesis of congenital heart block?

    Science.gov (United States)

    Li, J M; Horsfall, A C; Maini, R N

    1995-03-01

    Cross-reactions between maternally derived autoantibodies and fetal cardiac antigens have been postulated to play a role in the pathogenesis of congenital heart block (CHB). We have explored the cross-reactivity of autoantibodies to the small ribonuclear autoantigens, La/SS-B and Ro/SS-A, with laminin, the major component of cardiac sarcolemmal membrane using affinity-purified antibodies from patients with Sjögren's syndrome (SS). Anti-La antibodies purified from eight of 10 patients cross-reacted significantly with mouse laminin by ELISA. In contrast, purified antibodies to Ro52 from the same 10 patients showed little or no binding to laminin. Laminin inhibited up to 70% binding of anti-La antibodies to La antigen, and La inhibited up to 65% binding of anti-La antibodies to laminin. The cross-reaction was further examined on cryosections of 10 human fetal hearts aged from 8.7 to 14.9 weeks of gestation, two normal adult hearts, and one pathological adult heart with a diagnosis of dilated cardiomyopathy. Anti-Ro52 antibodies did not bind to the surface of cardiac cells. However, anti-La antibodies from seven of 10 patients tested bound to the surface of fetal myocytes from hearts aged 9.4 to 14.9 weeks of gestation, and also to the myocytes from the pathological adult heart but not to normal adult hearts. Preincubation with La antigen abolished the binding of anti-La antibodies to the surface of adult heart myocytes with dilated cardiomyopathy, and pre-incubation with mouse laminin could partially block this binding. These results suggest that molecular mimicry between laminin and La, but not Ro52, may act as a target for specific maternal autoantibodies, and contribute to the pathogenesis of CHB at a critical stage during fetal cardiac development. PMID:7882552

  4. The use of a liquid phase blocking ELISA kit for detection of antibodies against foot-and-mouth disease virus in Colombia

    International Nuclear Information System (INIS)

    The objective of this study was to undertake an interlaboratory comparison of a liquid phase blocking ELISA for detection of antibodies to FMD virus. For that purpose sera from 120 vaccinated, 120 infected and 120 FMD negative cattle were tested. All sera were tested in a screening assay at a dilution of 1/32. Positive sera were tested in a titration assay (1/10, 1/50, 1/250, 1/1250). For serotype O1 Cruzeiro 108 sera from the FMD-free group were classified as negatives giving a specificity of 90%. For the same serotype the group of infected/vaccinated cattle gave 114/115 positive results showing a sensitivity of 95% respectively 96%. For serotype A24 Cruzeiro from the FMD-free group 85 sera were classified as negatives giving a specificity 71%. For the same serotype the group of infected/vaccinated cattle gave 90/99 positive results showing a sensitivity of 75% respectively 82%. The predictive value of the assay was good as results expected for the different serum categories were mainly confirmed in the test. Nevertheless a high number of plates were rejected due to 'outside limits' and further adjustments are necessary to obtain more reliable results. (author)

  5. Antibodies to P-selectin glycoprotein ligand-1 block dendritic cell-mediated enterovirus 71 transmission and prevent virus-induced cells death.

    Science.gov (United States)

    Ren, Xiao-Xin; Li, Chuan; Xiong, Si-Dong; Huang, Zhong; Wang, Jian-Hua; Wang, Hai-Bo

    2015-01-01

    P-selectin glycoprotein ligand-1 (PSGL-1) has been proved to serve as the functional receptor for enterovirus 71 (EV71). We found the abundant expression of PSGL-1 on monocyte-derived dendritic cells (MDDCs). However, we have previously demonstrated that MDDCs did not support efficient replication of EV71. Dendritic cells (DCs) have been described to be subverted by various viruses including EV71 for viral dissemination, we thus explore the potential contribution of PSGL-1 on DC-mediated EV71 transmission. We found that the cell-surface-expressing PSGL-1 on MDDCs mediated EV71 binding, and intriguingly, these loaded-viruses on MDDCs could be transferred to encountered target cells; Prior-treatment with PSGL-1 antibodies or interference with PSGL-1 expression diminished MDDC-mediated EV71 transfer and rescued virus-induced cell death. Our data uncover a novel role of PSGL-1 in DC-mediated EV71 spread, and provide an insight into blocking primary EV71 infection.

  6. Disruption of focal adhesion kinase and p53 interaction with small molecule compound R2 reactivated p53 and blocked tumor growth

    OpenAIRE

    Golubovskaya, Vita M.; Ho, Baotran; Zheng, Min; Magis, Andrew; Ostrov, David; Morrison, Carl; Cance, William G.

    2013-01-01

    Background Focal Adhesion Kinase (FAK) is a 125 kDa non-receptor kinase that plays a major role in cancer cell survival and metastasis. Methods We performed computer modeling of the p53 peptide containing the site of interaction with FAK, predicted the peptide structure and docked it into the three-dimensional structure of the N-terminal domain of FAK involved in the complex with p53. We screened small molecule compounds that targeted the site of the FAK-p53 interaction and identified compoun...

  7. Evaluation of the therapeutic efficacy of a VEGFR2-blocking antibody using sodium-iodide symporter molecular imaging in a tumor xenograft model

    Energy Technology Data Exchange (ETDEWEB)

    Cheong, Su-Jin; Lee, Chang-Moon; Kim, Eun-Mi [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Uhm, Tai-Boong [Faculty of Biological Science, Chonbuk National University, Jeonju-si, jeonbuk 561-756 (Korea, Republic of); Jeong, Hwan-Jeong, E-mail: jayjeong@chonbuk.ac.k [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Kim, Dong Wook; Lim, Seok Tae; Sohn, Myung-Hee [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of)

    2011-01-15

    Purpose: Vascular endothelial growth factor receptor 2-blocking antibody (DC101) has inhibitory effects on tumor growth and angiogenesis in vivo. The human sodium/iodide symporter (hNIS) gene has been shown to be a useful molecular imaging reporter gene. Here, we investigated the evaluation of therapeutic efficacy by molecular imaging in reporter gene transfected tumor xenografts using a gamma imaging system. Methods: The hNIS gene was transfected into MDA-MB-231 cells using Lipofectamine. The correlation between the number of MDA-MB-231-hNIS cells and the uptake of {sup 99m}Tc-pertechnetate or {sup 125}I was investigated in vitro by gamma imaging and counting. MDA-MB-231-hNIS cells were injected subcutaneously into mice. When the tumor volume reached 180-200 mm{sup 3}, we randomly assigned five animals to each of three groups representing different tumor therapies; no DC101 (control), 100 {mu}g, or 150 {mu}g DC101/mouse. One week and 2 weeks after the first injection of DC101, gamma imaging was performed. Mice were sacrificed 2 weeks after the first injection of DC101. The tumor tissues were used for reverse transcriptase-polymerase chain reaction (RT-PCR) and CD31 staining. Results: Uptake of {sup 125}I and {sup 99m}Tc-pertechnetate into MDA-MB-231-hNIS cells in vitro showed correlation with the number of cells. In DC101 treatment groups, the mean tumor volume was smaller than that of the control mice. Furthermore, tumor uptake of {sup 125}I was lower than in the controls. The CD31 staining and RT-PCR assay results showed that vessel formation and expression of the hNIS gene were significantly reduced in the tumor tissues of treatment groups. Conclusion: This study demonstrated the power of molecular imaging using a gamma imaging system for evaluating the therapeutic efficacy of an antitumor treatment. Molecular imaging systems may be useful in evaluation and development of effective diagnostic and/or therapeutic antibodies for specific target molecules.

  8. Biomimetic design of platelet adhesion inhibitors to block integrin α2β1-collagen interactions: I. Construction of an affinity binding model.

    Science.gov (United States)

    Zhang, Lin; Sun, Yan

    2014-04-29

    Platelet adhesion on a collagen surface through integrin α2β1 has been proven to be significant for the formation of arterial thrombus. However, the molecular determinants mediating the integrin-collagen complex remain unclear. In the present study, the dynamics of integrin-collagen binding and molecular interactions were investigated using molecular dynamics (MD) simulations and molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) analysis. Hydrophobic interaction is identified as the major driving force for the formation of the integrin-collagen complex. On the basis of the MD simulation and MM-PBSA results, an affinity binding model (ABM) of integrin for collagen is constructed; it is composed of five residues, including Y157, N154, S155, R288, and L220. The ABM has been proven to capture the major binding motif contributing 84.8% of the total binding free energy. On the basis of the ABM, we expect to establish a biomimetic design strategy of platelet adhesion inhibitors, which would be beneficial for the development of potent peptide-based drugs for thrombotic diseases. PMID:24697616

  9. Effects of alpha-tocopherol on superoxide production and plasma intercellular adhesion molecule-1 and antibodies to oxidized LDL in chronic smokers

    NARCIS (Netherlands)

    Tits, van L.J.; Waart, de F.; Hak-Lemmers, H.L.M.; Heijst, P.; Graaf, de J.; Demacker, P.N.; Stalenhoef, A.F.

    2001-01-01

    Antioxidants have been postulated to exert beneficial effects in atherosclerosis. Atherosclerosis is associated with raised plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and autoantibodies against oxidized low-density lipoprotein (oxLDL). It is not known whether antioxidants a

  10. Endothelial adhesion of synchronized gastric tumor cells changes during cell cycle transit and correlates with the expression level of CD44 splice variants

    Institute of Scientific and Technical Information of China (English)

    Anton Oertl; Jens Castein; Tobias Engl; Wolf-Dietrich Beecken; Dietger Jonas; Richard Melamed; Roman A. Blaheta

    2005-01-01

    AIM: To study adhesion capacity and CD44 expression of human gastric adenocarcinoma MKN45 cells at different stages of a first cell cycle.METHODS: MKN45 cells were synchronized by aphidicolin and assayed for adhesion to an endothelial cell (HUVEC)monolayer. Surface expression of CD44 and CD44 splice variants on MKN45 cells was evaluated by flow cytometry.Functional relevance of CD44 adhesion receptors was investigated by blocking studies using anti CD44 monoclonal antibodies or by hyaluronan digestion.RESULTS: Adhesion of MKN45 to HUVEC was increased during G2/M transit, after which adhesion returned to baseline levels with cell cycle completion. In parallel, CD44splice variants CD44v4, CD44v5, and CD44v7 were all upregulated on MKN45 during cell cycle progression with a maximum effect in G2/M. The function of CD44 surface receptors was assessed with specific receptor blocking monodonal antibodies or removal of hyaluronan by digestion with hyaluronidase. Both strategies inhibited tumor cell adhesion to HUVEC by nearly 50%, which indicates that MKN45-HUVEC-interaction is CD44 dependent.CONCLUSION: CD44 expression level is linked to the cell cycle in gastrointestinal tumor cells, which in turn leads to cell cyde dependent alterations of their adhesion behaviour to endothelium.

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

    Directory of Open Access Journals (Sweden)

    Bin Hu

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    with homologous FMDV, positive reactions were obtained in all but one case. In some of these cattle the antibody response was detected late in comparison to the non-vaccinated infected cattle. The test gave results that compared favourably with two commercial ELISA's when used to test sera from cattle, pigs......A blocking ELISA that differentiated foot-and-mouth disease virus (FMDV) infected animals from vaccinated animals was developed which uses baculovirus expressed FMDV 3ABC non-structural protein as antigen and monoclonal antibody against FMDV 3ABC non-structural protein as capture and detector...... antibody. Sera from naive, vaccinated and infected cattle, sheep and pigs were examined. The specificity of the test was high. Non-specific reactions observed in particular in sera of cattle and sheep could be removed by filtration and inactivation. Positive reactions were obtained for sera from cattle...

  13. Adhesive Categories

    DEFF Research Database (Denmark)

    Lack, Stephen; Sobocinski, Pawel

    2003-01-01

    We introduce adhesive categories, which are categories with structure ensuring that pushouts along monomorphisms are well-behaved. Many types of graphical structures used in computer science are shown to be examples of adhesive categories. Double-pushout graph rewriting generalises well...... to rewriting on arbitrary adhesive categories....

  14. Adhesive Categories

    DEFF Research Database (Denmark)

    Lack, Stephen; Sobocinski, Pawel

    2004-01-01

    We introduce adhesive categories, which are categories with structure ensuring that pushouts along monomorphisms are well-behaved. Many types of graphical structures used in computer science are shown to be examples of adhesive categories. Double-pushout graph rewriting generalises well...... to rewriting on arbitrary adhesive categories....

  15. Single-domain antibodies that compete with the natural ligand fibroblast growth factor block the internalization of the fibroblast growth factor receptor 1

    Energy Technology Data Exchange (ETDEWEB)

    Veggiani, Gianluca; Ossolengo, Giuseppe; Aliprandi, Marisa; Cavallaro, Ugo [IFOM-IEO Campus, Via Adamello 16, 20139 Milano (Italy); Marco, Ario de, E-mail: ario.demarco@ung.si [IFOM-IEO Campus, Via Adamello 16, 20139 Milano (Italy); Dept. Environmental Sciences, University of Nova Gorica (UNG), Vipavska 13, P.O. Box 301-SI-5000, Rozna Dolina, Nova Gorica (Slovenia)

    2011-05-20

    Highlights: {yields} Recombinant antibodies for FGFR1 were isolated from a llama naive library in VHH format. {yields} These antibodies compete with the natural ligand FGF-2 for the same epitope on FGFR1. {yields} The antibody competition inhibits the FGF-2-dependent internalization of FGFR1. -- Abstract: Single-domain antibodies in VHH format specific for fibroblast growth factor receptor 1 (FGFR1) were isolated from a phage-display llama naive library. In particular, phage elution in the presence of the natural receptor ligand fibroblast growth factor (FGF) allowed for the identification of recombinant antibodies that compete with FGF for the same region on the receptor surface. These antibodies posses a relatively low affinity for FGFR1 and were never identified when unspecific elution conditions favoring highly affine binders were applied to panning procedures. Two populations of competitive antibodies were identified that labeled specifically the receptor-expressing cells in immunofluorescence and recognize distinct epitopes. Antibodies from both populations effectively prevented FGF-dependent internalization and nuclear accumulation of the receptor in cultured cells. This achievement indicates that these antibodies have a capacity to modulate the receptor physiology and, therefore, constitute powerful reagents for basic research and a potential lead for therapeutic applications.

  16. Adhesion of ZAP-70+ chronic lymphocytic leukemia cells to stromal cells is enhanced by cytokines and blocked by inhibitors of the PI3-kinase pathway.

    Science.gov (United States)

    Lafarge, Sandrine T; Johnston, James B; Gibson, Spencer B; Marshall, Aaron J

    2014-01-01

    CLL cell survival and proliferation is enhanced through direct contact with supporting cells present in lymphoid tissues. PI3Ks are critical signal transduction enzymes controlling B cell survival and activation. PI3K inhibitors have entered clinical trials and show promising therapeutic activity; however, it is unclear whether PI3K inhibitor drugs differentially affect ZAP-70 positive versus negative CLL cells or target specific microenvironmental interactions. Here we provide evidence that CD40L+IL-4, IL-8 or IL-6 enhance adhesion to stromal cells, with IL-6 showing a selective effect on ZAP-70 positive cells. Stimulatory effects of IL-8 or IL-6 are fully reversed by PI3K inhibition, while the effects of CD40L+IL-4 are partially reversed. While CD40L+IL-4 is the only stimulation increasing CLL cell survival for all patient groups, IL-6 protects ZAP-70 positive cells from cell death induced by PI3K inhibition. Altogether, our results indicate that targeting the PI3K pathway can reverse protective CLL-microenvironment interactions in both ZAP-70 positive and negative CLL despite their differences in cytokine responsiveness.

  17. Acquisition of Functional Antibodies That Block the Binding of Erythrocyte-Binding Antigen 175 and Protection Against Plasmodium falciparum Malaria in Children

    Science.gov (United States)

    Irani, Vashti; Ramsland, Paul A.; Guy, Andrew J.; Siba, Peter M.; Mueller, Ivo; Richards, Jack S.; Beeson, James G.

    2015-01-01

    Background. The targets and mechanisms of human immunity to malaria are poorly understood, which poses a major barrier to malaria vaccine development. Antibodies play a key role in human immunity and may act by inhibiting receptor-binding functions of key merozoite invasion ligands. Antibodies to the major invasion ligand and vaccine candidate, erythrocyte-binding antigen 175 (EBA-175), have been linked with protection, but how these antibodies function has not been established. Methods. We developed 2 new assays that quantify the ability of antibodies to inhibit binding of EBA-175 to its erythrocyte receptor, glycophorin A, using either native or recombinant EBA-175. Binding-inhibitory antibodies were evaluated in a longitudinal cohort study of Papua New Guinean children and related to risk of malaria, age, infection status, and markers of parasite exposure. Results. Binding-inhibition assays (BIAs) were reproducible, and the 2 assays had a high level of agreement. Inhibitory antibodies were common among children, acquired in association with markers of increasing parasite exposure, and high in those children with active infection. Inhibitory antibodies correlated with total immunoglobulin G levels to the EBA-175 binding domain (region II). Importantly, binding-inhibitory antibodies were significantly associated with protection from symptomatic malaria when measured using either BIA. Conclusions. Findings suggest that naturally acquired binding-inhibitory antibodies are an important functional mechanism that contributes to protection against malaria and further supports the potential of EBA-175 as a vaccine candidate. Identifying vaccines and approaches that induce potent binding-inhibitory antibodies may be a valuable strategy in the development of highly efficacious malaria vaccines. PMID:26136391

  18. Cell adhesion, inflammation and therapy: Old ideas and a significant step forward

    Institute of Scientific and Technical Information of China (English)

    Roberto GONZ(A)LEZ-AMARO

    2011-01-01

    Cell-to-cell adhesion as well as the interaction of cells with the extracellular matrix are key phenomena in different physiological and pathological conditions,including embryogenesis,blood coagulation,lymphocyte homing,immune response,angiogenesis,metastasis,thrombosis and inflammation[1,2].Thus,it has been widely proposed that cell adhesion molecules are an important therapeutic target in a wide array of diseases with high impact on public health,including atherosclerosis,thromboembolic disorders,cancer,graft rejection and autoimmune inflammatory conditions[1,2].However,anti-adhesion therapy with either biological agents (mainly blocking monoclonal antibodies,mAb's) or chemical inhibitors (mainly synthetic peptides) has not yet fulfilled these expectations and has not been devoid of undesirable effects[3,4

  19. A novel, blocking, Fc-silent anti-CD40 monoclonal antibody prolongs nonhuman primate renal allograft survival in the absence of B cell depletion.

    Science.gov (United States)

    Cordoba, F; Wieczorek, G; Audet, M; Roth, L; Schneider, M A; Kunkler, A; Stuber, N; Erard, M; Ceci, M; Baumgartner, R; Apolloni, R; Cattini, A; Robert, G; Ristig, D; Munz, J; Haeberli, L; Grau, R; Sickert, D; Heusser, C; Espie, P; Bruns, C; Patel, D; Rush, J S

    2015-11-01

    CD40-CD154 pathway blockade prolongs renal allograft survival in nonhuman primates (NHPs). However, antibodies targeting CD154 were associated with an increased incidence of thromboembolic complications. Antibodies targeting CD40 prolong renal allograft survival in NHPs without thromboembolic events but with accompanying B cell depletion, raising the question of the relative contribution of B cell depletion to the efficacy of anti-CD40 blockade. Here, we investigated whether fully silencing Fc effector functions of an anti-CD40 antibody can still promote graft survival. The parent anti-CD40 monoclonal antibody HCD122 prolonged allograft survival in MHC-mismatched cynomolgus monkey renal allograft transplantation (52, 22, and 24 days) with accompanying B cell depletion. Fc-silencing yielded CFZ533, an antibody incapable of B cell depletion but still able to potently inhibit CD40 pathway activation. CFZ533 prolonged allograft survival and function up to a defined protocol endpoint of 98-100 days (100, 100, 100, 98, and 76 days) in the absence of B cell depletion and preservation of good histological graft morphology. CFZ533 was well-tolerated, with no evidence of thromboembolic events or CD40 pathway activation and suppressed a gene signature associated with acute rejection. Thus, use of the Fc-silent anti-CD40 antibody CFZ533 appears to be an attractive approach for preventing solid organ transplant rejection.

  20. E-cadherin mediates adhesion and endocytosis of Aspergillus fumigatus blastospores in human epithelial cells

    Institute of Scientific and Technical Information of China (English)

    XU Xiao-yong; SHI Yi; ZHANG Peng-peng; ZHANG Feng; SHEN Yu-ying; SU Xin; ZHAO Bei-lei

    2012-01-01

    Background Aspergillus fumigatus (A.fumigatus) is a ubiquitous saprophytic fungus responsible for the majority of invasive mold infections in patients undergoing chemotherapy,organ transplantation or with persistent neutropenia.This study aimed to determine the role of E-cadherin for adhesion and endocytosis of A.fumigatus blastospores in the human epithelial cell line A549.Methods A.fumigatus blastospores were incubated with the total protein of A549 to investigate the binding of E-cadherin and blastospores followed by an affinity purification procedure.After establishing the adhesion model,the adhesion and endocytosis of A.fumigatus blastospores by A549 cells were evaluated by down-regulating E-cadherin of A549 cells using blocking antibody or small interfering RNA (siRNA).Results E-cadherin was adhered to the surface of A.fumigatus blastospore.Adhesion and endocytosis of the blastospores were reduced by blocking or down-regulating E-cadherin in A549 cells.Conclusions E-cadherin is a receptor for adhesion and endocytosis of A.fumigatus blastospores in epithelial cells.This may open a new approach to treat this fungal infection.

  1. Single-chain antibody-based gene therapy: Inhibition of tumor growth by in situ production of phage-derived antibodies blocking functionally active sites of cell-associated matrices

    DEFF Research Database (Denmark)

    Sanz, Laura; Kristensen, Peter; Blanco, Belén;

    2002-01-01

    Experimental evidence suggests that blocking the interactions between endothelial cells and extracellular matrix (ECM) components may provide a potent and general strategy to inhibit tumor neovascularization. Based on these considerations, we have focused our efforts on laminin, component of the ...

  2. Activation of AMP-activated protein kinase attenuates hepatocellular carcinoma cell adhesion stimulated by adipokine resistin

    International Nuclear Information System (INIS)

    Resistin, adipocyte-secreting adipokine, may play critical role in modulating cancer pathogenesis. The aim of this study was to investigate the effects of resistin on HCC adhesion to the endothelium, and the mechanism underlying these resistin effects. Human SK-Hep1 cells were used to study the effect of resistin on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions as well as NF-κB activation, and hence cell adhesion to human umbilical vein endothelial cells (HUVECs). 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, was used to determine the regulatory role of AMPK on HCC adhesion to the endothelium in regard to the resistin effects. Treatment with resistin increased the adhesion of SK-Hep1 cells to HUVECs and concomitantly induced NF-κB activation, as well as ICAM-1 and VCAM-1 expressions in SK-Hep1 cells. Using specific blocking antibodies and siRNAs, we found that resistin-induced SK-Hep1 cell adhesion to HUVECs was through NF-κB-regulated ICAM-1 and VCAM-1 expressions. Moreover, treatment with AICAR demonstrated that AMPK activation in SK-Hep1 cells significantly attenuates the resistin effect on SK-Hep1 cell adhesion to HUVECs. These results clarify the role of resistin in inducing HCC adhesion to the endothelium and demonstrate the inhibitory effect of AMPK activation under the resistin stimulation. Our findings provide a notion that resistin play an important role to promote HCC metastasis and implicate AMPK may be a therapeutic target to against HCC metastasis

  3. Development of an ErbB4 monoclonal antibody that blocks neuregulin-1-induced ErbB4 activation in cancer cells.

    Science.gov (United States)

    Okazaki, Shogo; Nakatani, Fumi; Masuko, Kazue; Tsuchihashi, Kenji; Ueda, Shiho; Masuko, Takashi; Saya, Hideyuki; Nagano, Osamu

    2016-01-29

    The use of monoclonal antibodies (mAbs) for cancer therapy is one of the most important strategies for current cancer treatment. The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, which regulates cancer cell proliferation, survival, and migration, is a major molecular target for antibody-based therapy. ErbB4/HER4, which contains a ligand-binding extracellular region, is activated by several ligands, including neuregulins (NRGs), heparin-binding EGF-like growth factor, betacellulin and epiregulin. Although there are clinically approved antibodies for ErbB1 and ErbB2, there are no available therapeutic mAbs for ErbB4, and it is not known whether ErbB4 is a useful target for antibody-based cancer therapy. In this study, we developed an anti-ErbB4 mAb (clone P6-1) that suppresses NRG-dependent activation of ErbB4 and examined its effect on breast cancer cell proliferation in the extracellular matrix. PMID:26780728

  4. Comprehensive Analysis of the Therapeutic IgG4 Antibody Pembrolizumab: Hinge Modification Blocks Half Molecule Exchange In Vitro and In Vivo.

    Science.gov (United States)

    Yang, Xiaoyu; Wang, Fengqiang; Zhang, Ying; Wang, Larry; Antonenko, Svetlana; Zhang, Shuli; Zhang, Yi Wei; Tabrizifard, Mohammad; Ermakov, Grigori; Wiswell, Derek; Beaumont, Maribel; Liu, Liming; Richardson, Daisy; Shameem, Mohammed; Ambrogelly, Alexandre

    2015-12-01

    IgG4 antibodies are evolving as an important class of cancer immunotherapies. However, human IgG4 can undergo Fab arm (half molecule) exchange with other IgG4 molecules in vivo. The hinge modification by a point mutation (S228P) prevents half molecule exchange of IgG4. However, the experimental confirmation is still expected by regulatory agencies. Here, we report for the first time the extensive analysis of half molecule exchange for a hinge-modified therapeutic IgG4 molecule, pembrolizumab (Keytruda) targeting programmed death 1 (PD1) receptor that was approved for advanced melanoma. Studies were performed in buffer or human serum using multiple exchange partners including natalizumab (Tysabri) and human IgG4 pool. Formation of bispecific antibodies was monitored by fluorescence resonance energy transfer, exchange with Fc fragments, mixed mode chromatography, immunoassays, and liquid chromatography-mass spectrometry. The half molecule exchange was also examined in vivo in SCID (severe combined immunodeficiency) mice. Both in vitro and in vivo results indicate that the hinge modification in pembrolizumab prevented half molecule exchange, whereas the unmodified counterpart anti-PD1 wt showed active exchange activity with other IgG4 antibodies or self-exchange activity with its own molecules. Our work, as an example expected for meeting regulatory requirements, contributes to establish without ambiguity that hinge-modified IgG4 antibodies are suitable for biotherapeutic applications.

  5. Detection of Anti-Influenza A Nucleoprotein Antibodies in Pigs Using a Commercial Influenza Epitope-Blocking Enzyme-Linked Immunosorbent Assay Developed for Avian Species

    Science.gov (United States)

    Influenza virus causes acute respiratory disease in pigs and is of concern for its potential public health significance. Many subtypes of influenza virus have been isolated from pigs and the virus continues to evolve in swine populations. Current antibody assays have limited antigenic recognition ...

  6. Venous levels of shear support neutrophil-platelet adhesion and neutrophil aggregation in blood via P-selectin and beta2-integrin

    Science.gov (United States)

    Konstantopoulos, K.; Neelamegham, S.; Burns, A. R.; Hentzen, E.; Kansas, G. S.; Snapp, K. R.; Berg, E. L.; Hellums, J. D.; Smith, C. W.; McIntire, L. V.; Simon, S. I.

    1998-01-01

    BACKGROUND: After activation, platelets adhere to neutrophils via P-selectin and beta2-integrin. The molecular mechanisms and adhesion events in whole blood exposed to venous levels of hydrodynamic shear in the absence of exogenous activation remain unknown. METHODS AND RESULTS: Whole blood was sheared at approximately 100 s(-1). The kinetics of neutrophil-platelet adhesion and neutrophil aggregation were measured in real time by flow cytometry. P-selectin was upregulated to the platelet surface in response to shear and was the primary factor mediating neutrophil-platelet adhesion. The extent of neutrophil aggregation increased linearly with platelet adhesion to neutrophils. Blocking either P-selectin, its glycoprotein ligand PSGL-1, or both simultaneously by preincubation with a monoclonal antibody resulted in equivalent inhibition of neutrophil-platelet adhesion (approximately 30%) and neutrophil aggregation (approximately 70%). The residual amount of neutrophil adhesion was blocked with anti-CD11b/CD18. Treatment of blood with prostacyclin analogue ZK36374, which raises cAMP levels in platelets, blocked P-selectin upregulation and neutrophil aggregation to baseline. Complete abrogation of platelet-neutrophil adhesion required both ZK36374 and anti-CD18. Electron microscopic observations of fixed blood specimens revealed that platelets augmented neutrophil aggregation both by forming bridges between neutrophils and through contact-mediated activation. CONCLUSIONS: The results are consistent with a model in which venous levels of shear support platelet adherence to neutrophils via P-selectin binding PSGL-1. This interaction alone is sufficient to mediate neutrophil aggregation. Abrogation of platelet adhesion and aggregation requires blocking Mac-1 in addition to PSGL-1 or P-selectin. The described mechanisms are likely of key importance in the pathogenesis and progression of thrombotic disorders that are exacerbated by leukocyte-platelet aggregation.

  7. The pro-adhesive and pro-survival effects of glucocorticoid in human ovarian cancer cells.

    Science.gov (United States)

    Yin, Lijuan; Fang, Fang; Song, Xinglei; Wang, Yan; Huang, Gaoxiang; Su, Jie; Hui, Ning; Lu, Jian

    2016-07-01

    Cell adhesion to extracellular matrix (ECM) is controlled by multiple signaling molecules and intracellular pathways, and is pivotal for survival and growth of cells from most solid tumors. Our previous works demonstrated that dexamethasone (DEX) significantly enhances cell adhesion and cell resistance to chemotherapeutics by increasing the levels of integrin β1, α4, and α5 in human ovarian cancer cells. However, it is unclear whether the components of ECM or other membrane molecules are also involved in the pro-adhesive effect of DEX in ovarian cancer cells. In this study, we demonstrated that the treatment of cells with DEX did not change the expression of collagens (I, III, and IV), laminin, CD44, and its principal ligand hyaluronan (HA), but significantly increased the levels of intracellular and secreted fibronectin (FN). Inhibiting the expression of FN with FN1 siRNA or blocking CD44, another FN receptor, with CD44 blocking antibody significantly attenuated the pro-adhesion of DEX, indicating that upregulation of FN mediates the pro-adhesive effect of DEX by its interaction with CD44 besides integrin β1. Moreover, DEX significantly enhanced cell resistance to the chemotherapeutic agent paclitaxel (PTX) by activating PI-3K-Akt pathway. Finally, we found that DEX also significantly upregulated the expression of MUC1, a transmembrane glycoprotein. Inhibiting the expression of MUC1 with MUC1 siRNA significantly attenuated the DEX-induced effects of pro-adhesion, Akt-activation, and pro-survival. In conclusion, these results provide new data that upregulation of FN and MUC1 by DEX contributes to DEX-induced pro-adhesion and protects ovarian cancer cells from chemotherapy. PMID:27151574

  8. Biomechanics of P-selectin PSGL-1 bonds: Shear threshold and integrin-independent cell adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Zhihua; Goldsmith, Harry L.; MacIntosh, Fiona A.; Shankaran, Harish; Neelamegham, Sriram

    2006-03-01

    Platelet-leukocyte adhesion may contribute to thrombosis and inflammation. We examined the heterotypic interaction between unactivated neutrophils and either thrombin receptor activating peptide (TRAP) stimulated platelets or P-selectin bearing beads (Ps-beads) in suspension. Cone-plate viscometers were used to apply controlled shear rates from 14-3000/s. Platelet-neutrophil and bead-neutrophil adhesion analysis was performed using both flow cytometry and high-speed videomicroscopy. We observed that while blocking antibodies against either P-selectin or P-selectin glycoprotein ligand-1 (PSGL-1) alone inhibited platelet-neutrophil adhesion by ~60% at 140/s, these reagents completely blocked adhesion at 3000/s. Anti-Mac-1 alone did not alter platelet-neutrophil adhesion rates at any shear rate, though in synergy with selectin antagonists it abrogated cell binding. Unstimulated neutrophils avidly bound Ps-beads and activated platelets in an integrin-independent manner, suggesting that purely selectin-dependent cell adhesion is possible. In support of this, antagonists against P-selectin or PSGL-1 dissociated previously formed platelet-neutrophil and Ps-bead neutrophil aggregates under shear in a variety of experimental systems, including in assays performed with whole blood. In studies where medium viscosity and shear rate were varied, a subtle shear threshold for P-selectin PSGL-1 binding was also noted at shear rates<100/s and at force loading rates of ~300pN/sec. Results are discussed in light of biophysical computations that characterize the collision between unequal size particles in linear shear flow. Overall, our studies reveal an integrin-independent regime for cell adhesion that may be physiologically relevant.

  9. Transmission-blocking activity of antibodies to Plasmodium falciparum GLURP.10C chimeric protein formulated in different adjuvants

    DEFF Research Database (Denmark)

    Roeffen, Will; Theisen, Michael; van de Vegte-Bolmer, Marga;

    2015-01-01

    BACKGROUND: Plasmodium falciparum is transmitted from person to person by Anopheles mosquitoes after completing its sexual reproductive cycle within the infected mosquito. An efficacious vaccine holds the potential to interrupt development of the parasite in the mosquito leading to control...... the native Pfs48/45 protein in macrogametes/zygotes. Interestingly, the GLA-Alum combination adjuvant was the most potent inducer of TB antibodies based on serum collected after two immunizations. In agreement with previous observations, biological activity in the SMFA correlated well with the level of anti......-Pfs48/45 antibodies. CONCLUSION: The combined data provide a strong basis for entering the next phase of clinical grade R0.10C production and testing....

  10. [Fetal myocarditis associated with maternal anti-Ro and anti-La antibodies in the absence of atrioventricular block with good outcome].

    Science.gov (United States)

    De La Villeon, C-G; Dulac, Y; Ohanessian, G; Ziani, A; Paranon, S; Acar, P

    2010-10-01

    We report a case of fetal myocarditis without conductive abnormality in a pregnant woman with anti-Ro/La antibodies. Fetal echocardiography showed myocarditis with ventricular and valvular hyperechogenicity, which was confirmed by postnatal transthoracic echography. Treatment with dexamethasone (4 mg/day) was started in the 22nd week of gestation. The outcome was good, with the child remaining asymptomatic 2 years later. This observation describes one of the rare forms of fetal myocarditis with favorable outcome.

  11. The high incidence of anti-Ro/SSA and anti-p200 antibodies in female patients with connective tissue diseases confirms the importance of screening for congenital heart block-associated autoantibodies during pregnancy.

    Science.gov (United States)

    Cozzani, E; Agnoletti, Arianna Fay; Pappalardo, F; Schiavetti, I; Torino, A; Parodi, A

    2016-03-01

    It is known that anti-Ro/SSA positivity leads to higher risk of miscarriage and fetal cardiac malformations. Particularly, anti-p200 antibodies against a finer specificity of the Ro/SSA antigen, have been associated with congenital heart block. The aim of the study was to assess the frequency of anti-p200 among female patients with different connective tissue diseases and, among these, the relevance of anti-p200 values in patients with cutaneous diseases compared to systemic diseases. Anti-p200 were investigated in 110 anti-Ro/SSA positive female sera, sent to our laboratory between 2008 and 2014 with suspect of connective disease, by using ELISA testing. Positivity was found in 40.9 % samples, 34 of them showed a strong positivity (values ≥ 1.0, cut off = 0.7). Patients with systemic diseases were anti-p200 positive in the 45.9 % of cases while patients with cutaneous diseases were positive in the 24.0 % of cases. Positivity for anti-p200 antibodies was revealed in 24.0 % of patients with discoid lupus erythematosus; 100 % of patients with dermatomyositis; 40.0 % of patients with mixed connective tissue disease; 25.0 % of patients with rheumatoid arthritis; 100 % of patients with Sjögren's syndrome; 33.3 % of patients with subacute cutaneous lupus erythematosus; 42.9 % of patients with systemic lupus erythematosus; 80.0 % of patients with systemic sclerosis. No significant difference in anti-p200 prevalence was found between systemic and cutaneous involvement, nevertheless, considering only positive sera, the antibody titer was higher in systemic diseases rather than in cutaneous diseases (2.6 ± 1.7 and 1.7 ± 1.9; p = 0.041). The authors think screenings for anti-Ro/SSA and anti-p200 antibodies should be included in the laboratory checklist for pregnancy.

  12. The high incidence of anti-Ro/SSA and anti-p200 antibodies in female patients with connective tissue diseases confirms the importance of screening for congenital heart block-associated autoantibodies during pregnancy.

    Science.gov (United States)

    Cozzani, E; Agnoletti, Arianna Fay; Pappalardo, F; Schiavetti, I; Torino, A; Parodi, A

    2016-03-01

    It is known that anti-Ro/SSA positivity leads to higher risk of miscarriage and fetal cardiac malformations. Particularly, anti-p200 antibodies against a finer specificity of the Ro/SSA antigen, have been associated with congenital heart block. The aim of the study was to assess the frequency of anti-p200 among female patients with different connective tissue diseases and, among these, the relevance of anti-p200 values in patients with cutaneous diseases compared to systemic diseases. Anti-p200 were investigated in 110 anti-Ro/SSA positive female sera, sent to our laboratory between 2008 and 2014 with suspect of connective disease, by using ELISA testing. Positivity was found in 40.9 % samples, 34 of them showed a strong positivity (values ≥ 1.0, cut off = 0.7). Patients with systemic diseases were anti-p200 positive in the 45.9 % of cases while patients with cutaneous diseases were positive in the 24.0 % of cases. Positivity for anti-p200 antibodies was revealed in 24.0 % of patients with discoid lupus erythematosus; 100 % of patients with dermatomyositis; 40.0 % of patients with mixed connective tissue disease; 25.0 % of patients with rheumatoid arthritis; 100 % of patients with Sjögren's syndrome; 33.3 % of patients with subacute cutaneous lupus erythematosus; 42.9 % of patients with systemic lupus erythematosus; 80.0 % of patients with systemic sclerosis. No significant difference in anti-p200 prevalence was found between systemic and cutaneous involvement, nevertheless, considering only positive sera, the antibody titer was higher in systemic diseases rather than in cutaneous diseases (2.6 ± 1.7 and 1.7 ± 1.9; p = 0.041). The authors think screenings for anti-Ro/SSA and anti-p200 antibodies should be included in the laboratory checklist for pregnancy. PMID:26830903

  13. Inhibition of tumor vasculogenic mimicry and prolongation of host survival in highly aggressive gallbladder cancers by norcantharidin via blocking the ephrin type a receptor 2/focal adhesion kinase/paxillin signaling pathway.

    Directory of Open Access Journals (Sweden)

    Hui Wang

    Full Text Available Vasculogenic mimicry (VM is a newly-defined tumor microcirculation pattern in highly aggressive malignant tumors. We recently reported tumor growth and VM formation of gallbladder cancers through the contribution of the ephrin type a receptor 2 (EphA2/focal adhesion kinase (FAK/Paxillin signaling pathways. In this study, we further investigated the anti-VM activity of norcantharidin (NCTD as a VM inhibitor for gallbladder cancers and the underlying mechanisms. In vivo and in vitro experiments to determine the effects of NCTD on tumor growth, host survival, VM formation of GBC-SD nude mouse xenografts, and vasculogenic-like networks, malignant phenotypes i.e., proliferation, apoptosis, invasion and migration of GBC-SD cells. Expression of VM signaling-related markers EphA2, FAK and Paxillin in vivo and in vitro were examined by immunofluorescence, western blotting and real-time polymerase chain reaction (RT-PCR, respectively. The results showed that after treatment with NCTD, GBC-SD cells were unable to form VM structures when injecting into nude mouse, growth of the xenograft was inhibited and these observations were confirmed by facts that VM formation by three-dimensional (3-D matrix, proliferation, apoptosis, invasion, migration of GBC-SD cells were affected; and survival time of the xenograft mice was prolonged. Furthermore, expression of EphA2, FAK and Paxillin proteins/mRNAs of the xenografts was downregulated. Thus, we concluded that NCTD has potential anti-VM activity against human gallbladder cancers; one of the underlying mechanisms may be via blocking the EphA2/FAK/Paxillin signaling pathway.

  14. Adhesion of monocytes to medical steel as used for vascular stents is mediated by the integrin receptor Mac-1 (CD11b/CD18; alphaM beta2) and can be inhibited by semiconductor coating.

    Science.gov (United States)

    Schuler, Pia; Assefa, Dawit; Ylänne, Jari; Basler, Nicole; Olschewski, Manfred; Ahrens, Ingo; Nordt, Thomas; Bode, Christoph; Peter, Karlheinz

    2003-01-01

    Implantation of stents into stenosed arteries helps to restore normal blood flow in ischemic organs. However, limited biocompatibility of the applied medical steel can cause acute thrombosis and long-term restenosis. Adhesion of monocytes to stent metal may participate in those acute and long-term complications of stent placement. Based on described prominent electrochemical properties of the interaction between the monocyte integrin receptor Mac-1 and its various ligands, we hypothesized, that this receptor is a central mediator of monocyte adhesion to stent metal and that semiconductor coating of medical steel reduces monocyte adhesion. Adhesion of monocytes on L-316 stainless steel was directly evaluated by light microscopy. Mac-1 could be identified as mediator of monocyte adhesion, since cell adhesion could be blocked by anti-Mac-1-antibodies, including the cross-reacting anti-GPIIb/IIIa antibody fragment abciximab. To further prove the central role of Mac-1, two CHO cell lines were generated expressing recombinant Mac-1 either as wild type, resulting in a low affinity receptor, or mutant with a GFFKR deletion of the alpha(M) subunit, resulting in a high affinity receptor. Indeed, adhesion was specific for Mac-1 and dependent on the affinity state of this integrin. Finally, we could demonstrate that Mac-1-mediated adhesion of monocytes to stents can be significantly inhibited by silicon carbide coating of the stent metal. In conclusion, the integrin Mac-1 and its affinity state could be identified as major mediators of monocyte adhesion on medical steel. As therapeutic strategies, the blockade of Mac-1 by antibodies or silicon carbide coating of steel inhibits monocyte adhesion on stents. PMID:12881037

  15. 52-kDa Ro/SSA epitopes preferentially recognized by antibodies from mothers of children with neonatal lupus and congenital heart block

    OpenAIRE

    Fritsch, Christine; Hoebeke, Johan; Dali, Hayet; Isenberg, David A; Meyer, Olivier; Muller, Sylviane; Ricchiuti, Vincent

    2005-01-01

    Neonatal lupus erythematosus is a rare disorder caused by the transplacental passage of maternal autoantibodies. The 52-kDa Ro/SSA antigen (Ro52) ribonucleoprotein represents an antigenic target strongly associated with the autoimmune response in mothers whose children have neonatal lupus and cardiac conduction disturbances, mainly congenital heart block. The objective of this study was to identify putative Ro52/60-kDa Ro/SSA antigen (Ro60) epitopes associated with neonatal lupus and congenit...

  16. Antibodies and antisense oligodeoxynucleotides to μ-opioid receptors, selectively block the effects of μ-opioid agonists on intestinal transit and permeability in mice

    OpenAIRE

    Pol, Olga; Valle, Lluís; Sánchez-Blázquez, Pilar; Garzón, Javier; Puig, Margarita M.

    1999-01-01

    We have studied the effects of μ and δ opioids on intestinal function (permeability, PER; gastrointestinal transit, GIT), and their antagonism after the intracerebroventricular (i.c.v.) administration of specific antibodies (ABs) or antisense oligodeoxynucleotides (ODN) to μ-receptors (OR). Central versus peripheral site/s of action of subcutaneous (s.c.) μ-opioids, were also assessed.Male Swiss CD-1 mice were used. GIT was measured with charcoal and PER by the passage of 51Cr-EDTA from blood...

  17. TNF-alpha neutralizing antibody blocks thermal sensitivity induced by compound 48/80-provoked mast cell degranulation [v1; ref status: indexed, http://f1000r.es/1mq

    Directory of Open Access Journals (Sweden)

    Devavani Chatterjea

    2013-08-01

    Full Text Available Background:  Neuro-inflammatory circuits in the tissue regulate the complex pathophysiology of pain.  Protective nociceptive pain serves as an early warning system against noxious environmental stimuli.  Tissue-resident mast cells orchestrate the increased thermal sensitivity following injection of basic secretagogue compound 48/80 in the hind paw tissues of ND4 mice.  Here we investigated the effects of pre-treatment with TNF-α neutralizing antibody on compound 48/80-provoked thermal hyperalgesia.  Methods:  We treated ND4 Swiss male mice with intravenous anti-TNF-α antibody or vehicle 30 minutes prior to bilateral, intra-plantar compound 48/80 administration and measured changes in the timing of hind paw withdrawal observed subsequent to mice being placed on a 51oC hotplate.  We also assessed changes in tissue swelling, TNF-α gene expression and protein abundance, mast cell degranulation, and neutrophil influx in the hind paw tissue.  Findings:  We found that TNF-α neutralization significantly blocked thermal hyperalgesia, and reduced early tissue swelling. TNF-α neutralization had no significant effect on mast cell degranulation or neutrophil influx into the tissue, however.  Moreover, no changes in TNF-α protein or mRNA levels were detected within 3 hours of administration of compound 48/80.  Interpretation:  The neutralizing antibodies likely target pre-formed TNF-α including that stored in the granules of tissue-resident mast cells. Pre-formed TNF-α, released upon degranulation, has immediate effects on nociceptive signaling prior to the induction of neutrophil influx.  These direct effects on nociceptors are abrogated by TNF-α blockade resulting in compromised nociceptive withdrawal responses to acute, harmful environmental stimuli.

  18. TNF-alpha neutralizing antibody blocks thermal sensitivity induced by compound 48/80-provoked mast cell degranulation [v2; ref status: indexed, http://f1000r.es/1w5

    Directory of Open Access Journals (Sweden)

    Devavani Chatterjea

    2013-09-01

    Full Text Available Background: Neuro-inflammatory circuits in the tissue regulate the complex pathophysiology of pain. Protective nociceptive pain serves as an early warning system against noxious environmental stimuli. Tissue-resident mast cells orchestrate the increased thermal sensitivity following injection of basic secretagogue compound 48/80 in the hind paw tissues of ND4 mice. Here we investigated the effects of pre-treatment with TNF-α neutralizing antibody on compound 48/80-provoked thermal hyperalgesia. Methods: We treated ND4 Swiss male mice with intravenous anti-TNF-α antibody or vehicle 30 minutes prior to bilateral, intra-plantar compound 48/80 administration and measured changes in the timing of hind paw withdrawal observed subsequent to mice being placed on a 51oC hotplate. We also assessed changes in tissue swelling, TNF-α gene expression and protein abundance, mast cell degranulation, and neutrophil influx in the hind paw tissue. Findings: We found that TNF-α neutralization significantly blocked thermal hyperalgesia, and reduced early tissue swelling. TNF-α neutralization had no significant effect on mast cell degranulation or neutrophil influx into the tissue, however. Moreover, no changes in TNF-α protein or mRNA levels were detected within 3 hours of administration of compound 48/80. Interpretation:  The neutralizing antibodies likely target pre-formed TNF-α including that stored in the granules of tissue-resident mast cells. Pre-formed TNF-α, released upon degranulation, has immediate effects on nociceptive signaling prior to the induction of neutrophil influx. These early effects on nociceptors are abrogated by TNF-α blockade, resulting in compromised nociceptive withdrawal responses to acute, harmful environmental stimuli.

  19. Differences between primed allogeneic T-cell responses and the primary mixed leucocyte reaction. Primed T cells become independent of the blocking effects of monoclonal antibodies against IL-1 beta and the CD5, CD11a (LFA-1), and CD11c (p 150,95) molecules

    DEFF Research Database (Denmark)

    Ødum, Niels; Hofmann, B; Morling, N;

    1988-01-01

    monoclonal antibodies (MoAb) directed against (i) adhesion molecules belonging to the CD11 cluster of leucocyte antigens (CD11a, LFA-1; CD11b, MAC1 = CR3; and CD11c, p 150,95); (ii) various T cell-related antigens (CD2, CD4, CD5 and CD8); and (iii) recombinant IL-1 beta. The CD5-, CD11a- and CD11c...

  20. Thyroid Antibodies

    Science.gov (United States)

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

  1. Further characterization of a high affinity thyrotropin binding site on the rat thyrotropin receptor which is an epitope for blocking antibodies from idiopathic myxedema patients but not thyroid stimulating antibodies from Graves' patients.

    Science.gov (United States)

    Kosugi, S; Ban, T; Akamizu, T; Kohn, L D

    1991-10-31

    Cysteine 390 of the rat thyrotropin (TSH) receptor, when mutated to serine, results in a receptor with a reduced ability of TSH to bind and increase cAMP levels but a preserved ability of thyroid stimulating autoantibodies (TSAbs) from hyperthyroid Graves' patients to increase cAMP levels. The ability of receptor autoantibodies from hypothyroid patients with idiopathic myxedema to inhibit the TSAb activity which is preserved is, however, like TSH binding, significantly reduced. Cysteine 390, together with tyrosine 385, thus appears to be an important determinant in a high affinity TSH binding site which is an epitope for receptor autoantibodies which block TSH or TSAb action and cause hypothyroidism rather than TSAbs which increase cAMP levels and are associated with hyperthyroidism. Threonine 388 and aspartic acid 403 may contribute to this ligand interaction site. PMID:1719963

  2. Extracellular matrix-anchored serum amyloid A preferentially induces mast cell adhesion.

    Science.gov (United States)

    Hershkoviz, R; Preciado-Patt, L; Lider, O; Fridkin, M; Dastych, J; Metcalfe, D D; Mekori, Y A

    1997-07-01

    Mast cells are known to accumulate in various inflammatory processes, some of which are known to be associated with increased local and systemic levels of acute-phase reactants such as serum amyloid A (SAA) or with amyloid deposition. The mechanism(s) by which mast cells are recruited to these sites, however, has not been fully elucidated. It has recently been shown that SAA interacts with extracellular matrix (ECM) components and thereby acts as a chemoattractant and regulator of immune cell migration. On the basis of these observations, we examined the effect of SAA on mast cell adhesion to ECM, an essential step in cellular transmigration. We could first demonstrate strong specific binding of recombinant human SAA (rSAA) to murine mast cells using flow cytometry. Moreover, radiolabeled rSAA was found to bind, in a saturable manner, to mast cells, reaching a binding affinity of 10(-8) M. When immobilized by preincubation with ECM, SAA or its proteolytically degraded amyloid A fragment (amino acid residues 2-82), which contains RGD-related adhesion motif but not the COOH-terminal portion of SAA (amino acid residues 77-104), induced the adhesion of resting mast cells to ECM or laminin. SAA and AA, in soluble or immobilized forms, did not activate mast cells to release mediators. Mast cell adhesion to the immobilized ECM-SAA complex appeared to occur through an integrin recognition, inasmuch as adhesion was calcium dependent and could be blocked by an RGD-containing peptide or by anti-CD29 monoclonal antibody. Genistein also inhibited adhesion, indicating that tyrosine kinase activity was involved. These data suggest that SAA bound to ECM may serve as an important inducer of mast cell adhesion, thus regulating mast cell recruitment and accumulation at these sites, which in turn could potentiate further pathology. PMID:9252455

  3. Inhibition of Spontaneous Breast Cancer Metastasis by Anti—Thomsen-Friedenreich Antigen Monoclonal Antibody JAA-F11

    Directory of Open Access Journals (Sweden)

    Jamie Heimburg

    2006-11-01

    Full Text Available Thomsen-Friedenreich antigen (TF-Ag is expressed in many carcinomas, including those of the breast, colon, bladder, prostate. TF-Ag is important in adhesion and metastasis and as a potential immunotherapy target. We hypothesized that passive transfer of JAAF11, an anti -TF-Ag monoclonal antibody, may create a survival advantage for patients with TIF-Ag -expressing tumors by cytotoxicity, blocking of tumor cell adhesion, inhibition of metastasis. This was tested using in vitro models of tumor cell growth; cytotoxicity assays; in vitro, ex vivo, in vivo models of cancer metastasis; and, finally, in vivo effects in mice with metastatic breast cancer. Unlike some anti-TF-Ag antibodies, JAA-F11 did not enhance breast carcinoma cell growth. JAA-F11 did not induce the killing of 4T1 tumor cells through complement-dependent cytotoxicity or apoptotic mechanisms. However, JAA-F11 blocked the stages of metastasis that involve the adhesion of human breast carcinoma cells to human endothelial cells (human umbilical vein endothelial cells and human bone marrow endothelial cells 60 in in vitro static adhesion models, in a perfused ex vivo model, in murine lung vasculature in an in vivo metastatic deposit formation assay. JAA-F11 significantly extended the median survival time of animals bearing metastatic 4T1 breast tumors and caused a > 50% inhibition of lung metastasis.

  4. Antibodies from malaria-exposed pregnant women recognize trypsin resistant epitopes on the surface of Plasmodium falciparum-infected erythrocytes selected for adhesion to chondroitin sulphate A

    DEFF Research Database (Denmark)

    Sharling, Lisa; Enevold, Anders; Sowa, Kordai M P;

    2004-01-01

    . falciparum clone FCR3 cultures were used to assay surface IgG binding before and after selection of the parasite for adhesion to CSA. The effect of proteolytic digestion of parasite erythrocyte surface antigens on surface IgG binding and adhesion to CSA and hyaluronic acid (HA) was also studied. RESULTS: P...

  5. Mussel adhesive enhances the immobilization of human chorionic gonadotrophin to a solid support.

    Science.gov (United States)

    Burzio, V A; Silva, T; Pardo, J; Burzio, L O

    1996-10-15

    Polystyrene microtiter plates coated with 0.30 microgram/ well of the adhesive polyphenolic protein purified from the mussel Aulacomya ater showed enhanced capacity to immobilize antigens such as human chorionic gonadotrophin (hCG). Uncoated and coated wells were activated with different amounts of hCG (from 2 to 500 ng), blocked with bovine serum albumin, and tested with anti-hCG monoclonal antibodies and antimouse IgG conjugated with peroxidase. The reading at 492 nm of the uncoated wells activated with 500 ng of hCG was similar to that obtained with coated wells but using 5 to 10 ng of antigen. The coating procedure also resulted in better sensitivity to detect low concentration of monoclonal antibodies and better signal-to-noise ratio. The capacity of the mussel coating to immobilize hCG, as well as the immunoreactivity of the attached antigen, remained stable for several months. PMID:8921186

  6. Tumor cell adhesion to endothelial cells is increased by endotoxin via an upregulation of beta-1 integrin expression.

    LENUS (Irish Health Repository)

    Andrews, E J

    2012-02-03

    BACKGROUND: Recent studies have demonstrated that metastatic disease develops from tumor cells that adhere to endothelial cells and proliferate intravascularly. The beta-1 integrin family and its ligand laminin have been shown to be important in tumor-to-endothelial cell adhesion. Lipopolysaccharide (LPS) has been implicated in the increased metastatic tumor growth that is seen postoperatively. We postulated that LPS increases tumor cell expression of beta-1 integrins and that this leads to increased adhesion. METHODS: The human metastatic colon cancer cell line LS174T was labeled with an enhanced green fluorescent protein (eGFP) using retroviral transfection. Cell cultures were treated with LPS for 1, 2, and 4 h (n = 6 each) and were subsequently cocultured for 30 or 120 min with confluent human umbilical vein endothelial cells (HUVECs), to allow adherence. Adherent tumor cells were counted using fluorescence microscopy. These experiments were carried out in the presence or absence of a functional blocking beta-1 integrin monoclonal antibody (4B4). Expression of beta-1 integrin and laminin on tumor and HUVECs was assessed using flow cytometric analysis. Tumor cell NF-kappaB activation after incubation with LPS was measured. RESULTS: Tumor cell and HUVEC beta-1 integrin expression and HUVEC expression of laminin were significantly (P < 0.05) enhanced after incubation with LPS. Tumor cell adhesion to HUVECs was significantly increased. Addition of the beta-1 integrin blocking antibody reduced tumor cell adhesion to control levels. LPS increased tumor cell NF-kappaB activation. CONCLUSIONS: Exposure to LPS increases tumor cell adhesion to the endothelium through a beta-1 integrin-mediated pathway that is NF-kappaB dependent. This may provide a target for immunotherapy directed at reducing postoperative metastatic tumor growth.

  7. CD4 binding to major histocompatibility complex class II antigens induces LFA-1-dependent and -independent homotypic adhesion of B lymphocytes.

    Science.gov (United States)

    Kansas, G S; Cambier, J C; Tedder, T F

    1992-01-01

    T helper cells recognize processed antigen (Ag) in the context of major histocompatibility complex (MHC) class II antigens present on the surface of B cells and other Ag-presenting cells. This interaction is mediated through the T cell receptor complex with associate recognition of class II molecules by the CD4 molecule. In this study, the binding of a soluble recombinant CD4/Ig heavy chain fusion protein (CD4-gamma 3) or monoclonal antibody (mAb) to class II antigens on human B cells was shown to induce rapid and specific homotypic adhesion of B cells and most B lymphoblastoid cell lines. mAb reactive with CD4 inhibited CD4-gamma 3-induced adhesion and a mutant B lymphoblastoid cell line deficient in class II antigens failed to respond. Induction of homotypic adhesion was dependent on energy metabolism and a functional cytoskeleton, and class II+ pre-B cells did not exhibit adhesion in response to these stimuli, suggesting that cross-linking of class II molecules generated a transmembrane signal and did not simply aggregate cells. In addition, MHC class II-induced adhesion was Fc receptor independent, as 15 mAb of different Ig isotypes reactive with HLA-D or HLA-DQ gene products induced adhesion. Anti-class II mAb and CD4-gamma 3 were able to induce adhesion at concentrations as low as 10 ng/ml and 100 ng/ml, respectively. Suboptimal stimulation of B cell lines through HLA-D antigens induced homotypic adhesion that was dependent on the activation of LFA-1 (CD11a/CD18), and which could be blocked by specific mAb. However, at greater signal strengths, adhesion was not blocked by mAb against the known adhesion receptors, suggesting the induction of a novel adhesion pathway. Consistent with this, homotypic adhesion induced by engagement of MHC class II antigens was observed with LFA-1-deficient B cell lines, and was independent of CD49d or CD18 expression. Thus, the direct engagement of B cell class II antigens by CD4 is likely to generate transmembrane signals which

  8. Engagement of PSGL-1 enhances β2-integrin-involved adhesion of neutrophils to recombinant ICAM-1

    Institute of Scientific and Technical Information of China (English)

    Xiao-guang WANG; Yan-ping CHENG; Xue-qing BA

    2006-01-01

    Aim: The interactions of selectins and their ligands initiate the process of leukocyte migrating into inflamed tissue. P-selectin glycoprotein ligand 1 (PSGL-1) is the best characterized ligand of selectins, and has been demonstrated to mediate the adhesion of leukocytes to all three selectins in vivo. PSGL-1 not only functions as an anchor molecule to capture the leukocytes to the activated endothelial cells by its interaction with selectins, but also transduces the signals to activate leukocytes. Our present work aimed to investigate the mechanism by which PSGL-1-mediated signal activates neutrophils and enhances the adhesion to the endothelial cells. Methods: We detected the effects of the engagement of PSGL-1 with monoclonal antibodies (mAb) or P-selectin on the adhesion of neutrophils to the recombinant intercellular adhesion molecule-1 (ICAM-1), and on the expression of β2-integrin. Additionally, the role of cytoskeleton in these process was studied by using inhibitor cytochalasin B. Results: The engagement of PSGL-1 increased the expression of β2-integrin on the surface of neutrophils and enhanced the adhesion of neutrophils to the recombinant ICAM-1. mAb against CD 18 impaired the adhesion of PSGL-1 -engaged neutrophils to ICAM-1. Moreover, the inhibitor cytochalasin B largely blocked the increase of CD 18 expression as well as the adhesion of PSGL-1-engaged neutrophils to ICAM-1. Conclusion: The PSGL-1-transduced signals can enhance β2-integrin-involved adhesion of neutrophils to the recombinant ICAM-1, and this process depends on the dynamics of cytoskeleton.

  9. Adhesion and Cohesion

    Directory of Open Access Journals (Sweden)

    J. Anthony von Fraunhofer

    2012-01-01

    Full Text Available The phenomena of adhesion and cohesion are reviewed and discussed with particular reference to dentistry. This review considers the forces involved in cohesion and adhesion together with the mechanisms of adhesion and the underlying molecular processes involved in bonding of dissimilar materials. The forces involved in surface tension, surface wetting, chemical adhesion, dispersive adhesion, diffusive adhesion, and mechanical adhesion are reviewed in detail and examples relevant to adhesive dentistry and bonding are given. Substrate surface chemistry and its influence on adhesion, together with the properties of adhesive materials, are evaluated. The underlying mechanisms involved in adhesion failure are covered. The relevance of the adhesion zone and its importance with regard to adhesive dentistry and bonding to enamel and dentin is discussed.

  10. Heart Block

    Science.gov (United States)

    ... the signal causes the heart to contract and pump blood. Heart block occurs if the electrical signal is ... degree heart block limits the heart's ability to pump blood to the rest of the body. This type ...

  11. Population Blocks.

    Science.gov (United States)

    Smith, Martin H.

    1992-01-01

    Describes an educational game called "Population Blocks" that is designed to illustrate the concept of exponential growth of the human population and some potential effects of overpopulation. The game material consists of wooden blocks; 18 blocks are painted green (representing land), 7 are painted blue (representing water); and the remaining…

  12. 淋巴细胞注射治疗复发性流产且封闭抗体为阴性的50例患者的临床分析%Clinical analysis of lymphocyte injection treatment for 50 recurrent spontaneous abortion patients with negative blocking antibody

    Institute of Scientific and Technical Information of China (English)

    徐珊珊

    2015-01-01

    Objective To explore the influence of lymphocyte injection treatment on recurrent spontaneous abortion patients with negative blocking antibody. Methods A total of 50 diagnosed recurrent spontaneous abortion patients due to lack of blocking recurrent were randomly divided into observation group with 25 cases (lymphocyte injection treatment) and control group with 25 cases (symptomatic treatment by integrated traditional Chinese and Western medicines). Treatment conditions were compared between the two groups. Results There were statistically significant differences of gestation situation, positive rate of blocking antibody, and quality of gestational blocking antibody after immunization between the two groups (P<0.05). Conclusion The effect of lymphocyte injection treatment is precise for treating recurrent spontaneous abortion patients with negative blocking antibody, and this method can reduce degree of risk.%目的:探讨淋巴细胞注射治疗对于复发性流产且封闭抗体为阴性的患者的影响。方法确诊为因缺乏封闭抗体而引发的复发性流产的患者50例,随机分成观察组25例(淋巴细胞注射治疗)和对照组25例(中西医结合对症治疗),对比两组患者的治疗情况。结果两组患者在妊娠情况、产生封闭抗体的阳性率、免疫后妊娠的封闭抗体的性质方面相比差异具有统计学意义(P<0.05)。结论淋巴细胞注射治疗复发性流产且封闭抗体呈阴性的患者效果明显,风险程度降低。

  13. Advanced adhesives in electronics

    CERN Document Server

    Bailey, C

    2011-01-01

    Adhesives are widely used in the manufacture of electronic devices to act as passive and active components. Recently there has been considerable interest in the use of conductive adhesives. This book reviews key types of conductive adhesives, processing methods, properties and the way they can be modelled as well as potential applications.$bAdhesives for electronic applications serve important functional and structural purposes in electronic components and packaging, and have developed significantly over the last few decades. Advanced adhesives in electronics reviews recent developments in adhesive joining technology, processing and properties. The book opens with an introduction to adhesive joining technology for electronics. Part one goes on to cover different types of adhesive used in electronic systems, including thermally conductive adhesives, isotropic and anisotropic conductive adhesives and underfill adhesives for flip-chip applications. Part two focuses on the properties and processing of electronic ...

  14. Anti-β2GPI antibodies stimulate endothelial cell microparticle release via a nonmuscle myosin II motor protein-dependent pathway.

    Science.gov (United States)

    Betapudi, Venkaiah; Lominadze, George; Hsi, Linda; Willard, Belinda; Wu, Meifang; McCrae, Keith R

    2013-11-28

    The antiphospholipid syndrome is characterized by thrombosis and recurrent fetal loss in patients with antiphospholipid antibodies (APLAs). Most pathogenic APLAs are directed against β2-glycoprotein I (β2GPI), a plasma phospholipid binding protein. One mechanism by which circulating antiphospholipid/anti-β2GPI antibodies may promote thrombosis is by inducing the release of procoagulant microparticles from endothelial cells. However, there is no information available concerning the mechanisms by which anti-β2GPI antibodies induce microparticle release. In seeking to identify proteins phosphorylated during anti-β2GPI antibody-induced endothelial activation, we observed phosphorylation of nonmuscle myosin II regulatory light chain (RLC), which regulates cytoskeletal assembly. In parallel, we observed a dramatic increase in the formation of filamentous actin, a two- to fivefold increase in the release of endothelial cell microparticles, and a 10- to 15-fold increase in the expression of E-selectin, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and tissue factor messenger RNA. Microparticle release, but not endothelial cell surface E-selectin expression, was blocked by inhibiting RLC phosphorylation or nonmuscle myosin II motor activity. These results suggest that distinct pathways, some of which mediate cytoskeletal assembly, regulate the endothelial cell response to anti-β2GPI antibodies. Inhibition of nonmuscle myosin II activation may provide a novel approach for inhibiting microparticle release by endothelial cells in response to anti-β2GPI antibodies. PMID:23954892

  15. Apparent genetic difference between hypothyroid patients with blocking-type thyrotropin receptor antibody and those without, as shown by restriction fragement length polymorphism analyses of HLA-DP loci

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Daisuke; Sugawa, Hideo; Akamizu, Takashi; Mori, Toru (Kyoto Univ. School of Medicine, Kyoto (Japan)); Sato, Kaoru; Inoko, Hidetoshi; Tsuji, Kimiyoshi (Tokai Univ. School of Medicine, Kanagawa (Japan)); Maeda, Masahiro (Nichirei Corp., Tokyo (Japan))

    1993-09-01

    HLA types in Japanese patients with primary hypothyroidism were analyzed to see whether those with blocking-type TSH receptor antibody (TSH-R BAb M) differed genetically from those with idiopathic myxedema (IM). HLA typings of -A, -B, -C, -DR, and -DQ (73 antigens) were performed serologically, and those of -D and -DP (29 antigens) were analyzed by the restriction fragment length polymorphism method. Thirty patients were studied with TSH-R BAb M, and 28 with IM. The data were analyzed and compared with previous results from 88 Graves' patients, 46 Hashimoto patients, and 186 control subjects. Overall, 192 patients with 4 autoimmune thyroid disorders showed a decrease in -Aw19 and an increase in -DQw4 (corrected P < 0.05) and significant associations of -Aw33, -Bw46, -Cw3, -DRw8, -DR9, and -DQw3. In TSH-R BAb M patients, increases in -B35, -Bw60, and -Dw8 and decreases in -DR4 and -DPw2 were seen, whereas IM patients showed increased -DPw2, -Bw61, and -Dw23. In comparisons between TSH-R-BAb M and IM, the difference in -DPw2 was highly significant. HLA-B35 differed significantly in these 2 types of hypothyroidism. In conclusion, TSH-R BAb M patients have decreased frequency of -DPw2 and are genetically similar to Graves' disease, whereas IM patients are characterized by high frequency of -DPw2 and are genetically similar to Hashimoto's thyroiditis. 39 refs., 2 figs., 3 tabs.

  16. Adhesion in microelectronics

    CERN Document Server

    Mittal, K L

    2014-01-01

    This comprehensive book will provide both fundamental and applied aspects of adhesion pertaining to microelectronics in a single and easily accessible source. Among the topics to be covered include; Various theories or mechanisms of adhesionSurface (physical or chemical) characterization of materials as it pertains to adhesionSurface cleaning as it pertains to adhesionWays to improve adhesionUnraveling of interfacial interactions using an array of pertinent techniquesCharacterization of interfaces / interphasesPolymer-polymer adhesionMetal-polymer adhesion  (metallized polymers)Polymer adhesi

  17. A Novel Domain Cassette Identifies Plasmodium falciparum PfEMP1 Proteins Binding ICAM-1 and Is a Target of Cross-Reactive, Adhesion-Inhibitory Antibodies

    DEFF Research Database (Denmark)

    Bengtsson, Anja; Jørgensen, Louise; Rask, Thomas Salhøj;

    2013-01-01

    -exposed children. Our study challenges earlier conclusions that group A PfEMP1 proteins are not central to ICAM-1-specific IE adhesion and support the feasibility of developing a vaccine preventing cerebral malaria by inhibiting cerebral IE sequestration. The Journal of Immunology, 2013, 190: 240-249....

  18. 单组分封闭异氰酸酯胶束/聚乙烯醇复合胶粘剂的制备及性能%Preparation and characterization of one-component blocked isocyanate micelle/PVA composite adhesive

    Institute of Scientific and Technical Information of China (English)

    邬洪川; 李志国; 白龙; 朱丽滨; 顾继友

    2015-01-01

    采用甲苯二异氰酸酯 TDI 、聚乙二醇(PEG)、二羟甲基丙酸(DMPA)以及封闭剂甲乙酮肟(MEKO)等为主要原料以及聚乙烯醇为复合组分制备了单组分封闭异氰酸酯胶束/聚乙烯醇 BIP/PVA 复合胶粘剂。系统研究了在加热条件下封闭胶束解封闭交联固化反应。考查了封闭异氰酸酯预聚胶束(BIP)对复合乳液稳定性,强度以及耐水性的影响。研究结果表明,复合胶粘剂的固化温度在120~125℃。随着BIP含量增加,复合胶粘剂强度和耐水性提高,但稳定性逐渐下降,当w BIP =15%时,可制得常温(20~30℃)存放3个月以上,干强度超过3.04 MPa,湿强度可达1.29 MPa的单组分BIP/PVA胶粘剂。()()()%The one-component blocked isocyanate micelle/PVA emulsions were prepared from toluene diisocyanate (TDI), polyethylene glycol (PEG), dimethylol propionic acid (DMPA), methyl ethyl ketone oxime (MEKO) as the blocking agent and polyvinyl alcohol (PVA) as the composite component. The deblocking and subsequent crosslinking reaction of the blocked emulsions was systematically researched. Furthermore, the effects of blocked isocyanate pre-polymer micelles (BIP) on the stability, water resistance and strength of the emulsions were investigated. The results showed that this composite adhesive was cured at between 120~125℃. With increasing BIP content, the strength and water-resistance of the composite adhesive was improved but its stability was gradually decreased. When the BIP content was 15 wt%, the storage time was over three months under the room temperature (20~30℃), and both the wet and dry strength reached 1.29 MPa and over 3.04 MPa,respectively..

  19. Novel strategies for the treatment of inflammatory bowel disease: Selective inhibition of cytokines and adhesion molecules

    Institute of Scientific and Technical Information of China (English)

    Kazuhiko Nakamura; Kuniomi Honda; Takahiro Mizutani; Hirotada Akiho; Naohiko Harada

    2006-01-01

    The etiology of inflammatory bowel disease (IBD) has not yet been clarified and immunosuppressive agents which non-specifically reduce inflammation and immunity have been used in the conventional therapies for IBD. Evidence indicates that a dysregulation of mucosal immunity in the gut of IBD causes an overproduction of inflammatory cytokines and trafficking of effector leukocytes into the bowel, thus leading to an uncontrolled intestinal inflammation. Such recent advances in the understanding of the pathogenesis of IBD created a recent trend of novel biological therapies which specifically inhibit the molecules involved in the inflammatory cascade. Major targets for such treatment are inflammatory cytokines and their receptors, and adhesion molecules. A chimeric anti-TNF-α monoclonal antibody, infliximab, has become a standard therapy for CD and it is also likely to be beneficial for UC. Several anti-TNF reagents have been developed but most of them seem to not be as efficacious as infliximab. A humanized anti-TNF monoclonal antibody, adalimumab may be useful for the treatment of patients who lost responsiveness or developed intolerance to infliximab.Antibodies against IL-12 p40 and IL-6 receptor could be alternative new anti-cytokine therapies for IBD. Antiinterferon-γ and anti-CD25 therapies were developed,but the benefit of these agents has not yet been established. The selective blocking of migration of leukocytes into intestine seems to be a nice approach.Antibodies against α4 integrin and α4β7 integrin showed benefit for IBD. Antisense oligonucleotide of intercellular adhesion molecule 1 (ICAM-1) may be efficacious for IBD. Clinical trials of such compounds have been either recently reported or are currently underway. In this article, we review the efficacy and safety of such novel biological therapies for IBD.

  20. Mapping of domains in human laminin using monoclonal antibodies: localization of the neurite-promoting site

    OpenAIRE

    1986-01-01

    Monoclonal antibodies were made against a truncated form of human laminin isolated from placenta. 12 antibodies were isolated and characterized. All antibodies stained basement membranes in placenta and immunoprecipitated laminin from media of cultured choriocarcinoma cells. Three antibodies, 3E5, 4C7, and 4E10, partially blocked the neurite-promoting activity of laminin. Addition of a second antibody, goat anti-mouse IgG, caused more complete blocking of the activity. Two of the blocking ant...

  1. Cellular adhesion molecules on endothelial cells participate in radiation-mediated inflammation

    International Nuclear Information System (INIS)

    protei expression following irradiation. E-selectin expression began to increase at 2 h, peaked at 4 to 6 h, and gradually returned to baseline at 20 h. In contrast, ICAM expression remained at baseline levels until 16 h after irradiation, and peak expression occurred at 24 to 36 h following irradiation. E-selectin expression increased at 4 h after exposure to 0.5 Gy and increased in a dose dependent manner up to 20 Gy, where a plateau was reached. In contrast, ICAM expression was not increased after x-ray doses below 5 Gy, but dose dependent increases occurred at 24 hours when treated with higher doses. Cells transfected with plasmid pTK-GH demonstrated no radiation induction, whereas those transfected with plasmid pE (-578 to +35)-GH had a 7-fold (HUVEC) to 10-fold (HMEC) increase in expression after irradiation as compared to untreated controls. Induction was prevented when the NFκB binding site was deleted from the E-selectin promoter. Nuclear proteins isolated at 15 min after irradiation had increased binding to the E-selectin NFkB binding site. Leukocyte adhesion to irradiated endothelial cells increased 4-fold at 4 hours after irradiation and this was blocked by antibodies to E-selectin. Conclusion: E-selectin induction in irradiated endothelial cells is NFkB dependent. Leukocyte binding to endothelial cells after irradiation is blocked by antibodies to E-selectin. Cellular adhesion molecule expression on irradiated endithelial cells may participate in inflammation during radiotherapy. Prevention and treatment of acute radiation injury using a new class of anti-inflammatory agents will be discussed

  2. Evidence for heterophilic adhesion of embryonic retinal cells and neuroblastoma cells to substratum-adsorbed NCAM

    OpenAIRE

    1992-01-01

    The adhesion of embryonic chicken retinal cells and mouse N2A neuroblastoma cells to purified embryonic chicken retinal NCAM adsorbed on a solid substratum was examined using a quantitative centrifugal adhesion assay. Both cell types adhered to NCAM and the adhesion was specifically inhibited by monovalent anti-NCAM antibody fragments. N2A cell adhesion depended on the amount of NCAM applied to the substratum, was cation independent, and was insensitive to treatment with the cytoskeletal pert...

  3. Zitongxi Block

    Institute of Scientific and Technical Information of China (English)

    1996-01-01

    @@ Zitongxi Block (Western Zitong Block), is located in Zitong County, northwest of Sichuan Province (as shown on Fig. 8 ). Geologically. it is situated in the Zitong Depression, southwest of the middle Longmenshan faulted and folded belt, covering an area of 1 830 km2. Transportation is very convenient. A crisscross network of highways run through the block and the Baocheng railway is nearby. The climate is moderate. Most area belongs to hilly land with the elevation of 500-600 m.The Tongjiang River runs across the area.

  4. Prevention of reovirus type 2-induced diabetes-like syndrome in DBA/1 suckling mice by treatment with antibodies against intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1.

    OpenAIRE

    Hayashi, T.; Yamamoto, S.; Onodera, T.

    1995-01-01

    Reovirus type 2-induced diabetes-like syndrome in suckling mice is considered to be an animal model for human insulin-dependent diabetes mellitus. We have previously demonstrated that immunopathologic pancreatic islet cell damage might be relevant to reovirus type 2 infection. In this study the involvement of adhesion molecules in the development of reovirus type 2-induced diabetes-like syndrome was examined. In infected mice infiltration of mononuclear cells mixed with polymorphonuclear leuc...

  5. Bacterial endotoxin enhances colorectal cancer cell adhesion and invasion through TLR-4 and NF-kappaB-dependent activation of the urokinase plasminogen activator system.

    LENUS (Irish Health Repository)

    Killeen, S D

    2009-05-19

    Perioperative exposure to lipopolysaccharide (LPS) is associated with accelerated metastatic colorectal tumour growth. LPS directly affects cells through Toll-like receptor 4 (TLR-4) and the transcription factor NF-kappaB. The urokinase plasminogen activator (u-PA) system is intimately implicated in tumour cell extracellular matrix (ECM) interactions fundamental to tumour progression. Thus we sought to determine if LPS directly induces accelerated tumour cell ECM adhesion and invasion through activation of the u-PA system and to elucidate the cellular pathways involved. Human colorectal tumour cell lines were stimulated with LPS. u-PA concentration, u-PA activity, active u-PA, surface urokinase plasminogen activator receptor (u-PAR) and TLR-4 expression were assessed by ELISA, colorimetric assay, western blot analysis and flow cytometry respectively. In vitro tumour cell vitronectin adhesion and ECM invasion were analysed by vitronectin adhesion assay and ECM invasion chambers. u-PA and u-PAR function was inhibited with anti u-PA antibodies or the selective u-PA inhibitors amiloride or WXC-340, TLR-4 by TLR-4-blocking antibodies and NF-kappaB by the selective NF-kappaB inhibitor SN-50. LPS upregulates u-PA and u-PAR in a dose-dependent manner, enhancing in vitro tumour cell vitronectin adhesion and ECM invasion by >40% (P<0.01). These effects were ameliorated by u-PA and u-PAR inhibition. LPS activates NF-kappaB through TLR-4. TLR-4 and NF-kappaB inhibition ameliorated LPS-enhanced u-PA and u-PAR expression, tumour cell vitronectin adhesion and ECM invasion. LPS promotes tumour cell ECM adhesion and invasion through activation of the u-PA system in a TLR-4- and NF-kappaB-dependent manner.

  6. Abrogation of junctional adhesion molecule-A expression induces cell apoptosis and reduces breast cancer progression.

    Directory of Open Access Journals (Sweden)

    Masato Murakami

    Full Text Available Intercellular junctions promote homotypic cell to cell adhesion and transfer intracellular signals which control cell growth and apoptosis. Junctional adhesion molecule-A (JAM-A is a transmembrane immunoglobulin located at tight junctions of normal epithelial cells of mammary ducts and glands. In the present paper we show that JAM-A acts as a survival factor for mammary carcinoma cells. JAM-A null mice expressing Polyoma Middle T under MMTV promoter develop significantly smaller mammary tumors than JAM-A positive mice. Angiogenesis and inflammatory or immune infiltrate were not statistically modified in absence of JAM-A but tumor cell apoptosis was significantly increased. Tumor cells isolated from JAM-A null mice or 4T1 cells incubated with JAM-A blocking antibodies showed reduced growth and increased apoptosis which paralleled altered junctional architecture and adhesive function. In a breast cancer clinical data set, tissue microarray data show that JAM-A expression correlates with poor prognosis. Gene expression analysis of mouse tumor samples showed a correlation between genes enriched in human G3 tumors and genes over expressed in JAM-A +/+ mammary tumors. Conversely, genes enriched in G1 human tumors correlate with genes overexpressed in JAM-A-/- tumors. We conclude that down regulation of JAM-A reduces tumor aggressive behavior by increasing cell susceptibility to apoptosis. JAM-A may be considered a negative prognostic factor and a potential therapeutic target.

  7. Natural killer cell cytotoxicity of breast cancer targets is enhanced by two distinct mechanisms of antibody-dependent cellular cytotoxicity against LFA-3 and HER2/neu.

    Science.gov (United States)

    Cooley, S; Burns, L J; Repka, T; Miller, J S

    1999-10-01

    Treatment of advanced breast cancer with autologous stem cell transplantation is limited by a high probability of disease relapse. In clinical trials, interleukin 2 (IL-2) alone can expand natural killer (NK) cells in vivo and increase their cytotoxic activity against breast cancer cell lines, but this increase is modest. Understanding the mechanisms that mediate NK cell lysis of breast cancer targets may lead to improvements of current immunotherapy strategies. NK cells from normal donors or patients receiving subcutaneous IL-2 were tested in cytotoxicity assays against five breast cancer cell lines. The role of adhesion molecules and antibodies that interact through Fc receptors on NK cells was explored. NK cell lysis of breast cancer targets is variable and is partially dependent on recognition through ICAM-1 and CD18. While blocking CD2 slightly decreased cytotoxicity, contrary to expectations, an antibody against CD58 (the ligand for CD2), failed to block killing and instead mediated an increased cytotoxicity that correlated with target density of CD58. The CD58 antibody-enhanced killing was dependent not only on FcRgammaIII but also on CD2 and ICAM-1/CD18. To further elucidate the mechanism of this CD58 antibody-dependent cellular cytotoxicity (ADCC), another antibody was tested. Trastuzumab (Herceptin), a humanized antibody against HER2/neu, mediated potent ADCC against all the HER2/neu positive breast cancer targets. Unlike CD58 antibody-mediated ADCC, Herceptin ADCC was minimally affected by blocking antibodies to CD2 or ICAM-1/CD18, which suggests a different mechanism of action. This study shows that multiple mechanisms are involved in NK cell lysis of breast cancer targets, that none of the targets are inherently resistant to killing, and that two distinct mechanisms of ADCC can target immunotherapy to breast cancer cells. PMID:10517495

  8. Influenza Virus Infection Induces Platelet-Endothelial Adhesion Which Contributes to Lung Injury.

    Science.gov (United States)

    Sugiyama, Michael G; Gamage, Asela; Zyla, Roman; Armstrong, Susan M; Advani, Suzanne; Advani, Andrew; Wang, Changsen; Lee, Warren L

    2015-12-04

    Lung injury after influenza infection is characterized by increased permeability of the lung microvasculature, culminating in acute respiratory failure. Platelets interact with activated endothelial cells and have been implicated in the pathogenesis of some forms of acute lung injury. Autopsy studies have revealed pulmonary microthrombi after influenza infection, and epidemiological studies suggest that influenza vaccination is protective against pulmonary thromboembolism; however, the effect of influenza infection on platelet-endothelial interactions is unclear. We demonstrate that endothelial infection with both laboratory and clinical strains of influenza virus increased the adhesion of human platelets to primary human lung microvascular endothelial cells. Platelets adhered to infected cells as well as to neighboring cells, suggesting a paracrine effect. Influenza infection caused the upregulation of von Willebrand factor and ICAM-1, but blocking these receptors did not prevent platelet-endothelial adhesion. Instead, platelet adhesion was inhibited by both RGDS peptide and a blocking antibody to platelet integrin α5β1, implicating endothelial fibronectin. Concordantly, lung histology from infected mice revealed viral dose-dependent colocalization of viral nucleoprotein and the endothelial marker PECAM-1, while platelet adhesion and fibronectin deposition also were observed in the lungs of influenza-infected mice. Inhibition of platelets using acetylsalicylic acid significantly improved survival, a finding confirmed using a second antiplatelet agent. Thus, influenza infection induces platelet-lung endothelial adhesion via fibronectin, contributing to mortality from acute lung injury. The inhibition of platelets may constitute a practical adjunctive strategy to the treatment of severe infections with influenza.IMPORTANCE There is growing appreciation of the involvement of the lung endothelium in the pathogenesis of severe infections with influenza virus. We have

  9. Influenza Virus Infection Induces Platelet-Endothelial Adhesion Which Contributes to Lung Injury.

    Science.gov (United States)

    Sugiyama, Michael G; Gamage, Asela; Zyla, Roman; Armstrong, Susan M; Advani, Suzanne; Advani, Andrew; Wang, Changsen; Lee, Warren L

    2016-02-01

    Lung injury after influenza infection is characterized by increased permeability of the lung microvasculature, culminating in acute respiratory failure. Platelets interact with activated endothelial cells and have been implicated in the pathogenesis of some forms of acute lung injury. Autopsy studies have revealed pulmonary microthrombi after influenza infection, and epidemiological studies suggest that influenza vaccination is protective against pulmonary thromboembolism; however, the effect of influenza infection on platelet-endothelial interactions is unclear. We demonstrate that endothelial infection with both laboratory and clinical strains of influenza virus increased the adhesion of human platelets to primary human lung microvascular endothelial cells. Platelets adhered to infected cells as well as to neighboring cells, suggesting a paracrine effect. Influenza infection caused the upregulation of von Willebrand factor and ICAM-1, but blocking these receptors did not prevent platelet-endothelial adhesion. Instead, platelet adhesion was inhibited by both RGDS peptide and a blocking antibody to platelet integrin α5β1, implicating endothelial fibronectin. Concordantly, lung histology from infected mice revealed viral dose-dependent colocalization of viral nucleoprotein and the endothelial marker PECAM-1, while platelet adhesion and fibronectin deposition also were observed in the lungs of influenza-infected mice. Inhibition of platelets using acetylsalicylic acid significantly improved survival, a finding confirmed using a second antiplatelet agent. Thus, influenza infection induces platelet-lung endothelial adhesion via fibronectin, contributing to mortality from acute lung injury. The inhibition of platelets may constitute a practical adjunctive strategy to the treatment of severe infections with influenza.IMPORTANCE There is growing appreciation of the involvement of the lung endothelium in the pathogenesis of severe infections with influenza virus. We have

  10. PH dependent adhesive peptides

    Science.gov (United States)

    Tomich, John; Iwamoto, Takeo; Shen, Xinchun; Sun, Xiuzhi Susan

    2010-06-29

    A novel peptide adhesive motif is described that requires no receptor or cross-links to achieve maximal adhesive strength. Several peptides with different degrees of adhesive strength have been designed and synthesized using solid phase chemistries. All peptides contain a common hydrophobic core sequence flanked by positively or negatively charged amino acids sequences.

  11. Ghost Block

    OpenAIRE

    Webb, Neil

    2011-01-01

    Filmed on the English south coast 'Ghost Block' depicts the uncanny and eerie atmosphere at the site of a WW2 coastal defence line. The concrete cubes were used as an anti-invasion blockade against potential landing forces. This protection line now slowly decaying and becoming enmeshed into the environment still acts as a defence to repel unwanted visitors. The area is a natural reserve to nesting birds that often lay eggs directly onto the beach surface. The blocks act as a final barrier ...

  12. Prevention of bacterial adhesion

    DEFF Research Database (Denmark)

    Klemm, Per; Vejborg, Rebecca Munk; Hancock, Viktoria

    2010-01-01

    that imposes selection pressure for resistant bacteria. New approaches are urgently needed. Targeting bacterial virulence functions directly is an attractive alternative. An obvious target is bacterial adhesion. Bacterial adhesion to surfaces is the first step in colonization, invasion, and biofilm formation....... As such, adhesion represents the Achilles heel of crucial pathogenic functions. It follows that interference with adhesion can reduce bacterial virulence. Here, we illustrate this important topic with examples of techniques being developed that can inhibit bacterial adhesion. Some of these will become...

  13. Particle adhesion and removal

    CERN Document Server

    Mittal, K L

    2015-01-01

    The book provides a comprehensive and easily accessible reference source covering all important aspects of particle adhesion and removal.  The core objective is to cover both fundamental and applied aspects of particle adhesion and removal with emphasis on recent developments.  Among the topics to be covered include: 1. Fundamentals of surface forces in particle adhesion and removal.2. Mechanisms of particle adhesion and removal.3. Experimental methods (e.g. AFM, SFA,SFM,IFM, etc.) to understand  particle-particle and particle-substrate interactions.4. Mechanics of adhesion of micro- and  n

  14. The talin head domain reinforces integrin-mediated adhesion by promoting adhesion complex stability and clustering.

    Directory of Open Access Journals (Sweden)

    Stephanie J Ellis

    2014-11-01

    Full Text Available Talin serves an essential function during integrin-mediated adhesion in linking integrins to actin via the intracellular adhesion complex. In addition, the N-terminal head domain of talin regulates the affinity of integrins for their ECM-ligands, a process known as inside-out activation. We previously showed that in Drosophila, mutating the integrin binding site in the talin head domain resulted in weakened adhesion to the ECM. Intriguingly, subsequent studies showed that canonical inside-out activation of integrin might not take place in flies. Consistent with this, a mutation in talin that specifically blocks its ability to activate mammalian integrins does not significantly impinge on talin function during fly development. Here, we describe results suggesting that the talin head domain reinforces and stabilizes the integrin adhesion complex by promoting integrin clustering distinct from its ability to support inside-out activation. Specifically, we show that an allele of talin containing a mutation that disrupts intramolecular interactions within the talin head attenuates the assembly and reinforcement of the integrin adhesion complex. Importantly, we provide evidence that this mutation blocks integrin clustering in vivo. We propose that the talin head domain is essential for regulating integrin avidity in Drosophila and that this is crucial for integrin-mediated adhesion during animal development.

  15. Epidural block

    Science.gov (United States)

    ... Drugs & Supplements Videos & Tools Español You Are Here: Home ... It numbs or causes a loss of feeling in the lower half your body. This lessens the pain of contractions during childbirth. An epidural block may also be used to ...

  16. Adhesion of Actinobacillus actinomycetemcomitans to a human oral cell line.

    OpenAIRE

    Mintz, K. P.; Fives-Taylor, P M

    1994-01-01

    Two quantitative, rapid assays were developed to study the adhesion of Actinobacillus actinomycetemcomitans, an oral bacterium associated with periodontal disease, to human epithelial cells. The human oral carcinoma cell line KB was grown in microtiter plates, and adherent bacteria were detected by an enzyme-linked immunosorbent assay with purified anti-A. actinomycetemcomitans serum and horseradish peroxidase-conjugated secondary antibody or [3H]thymidine-labeled bacteria. Adhesion was found...

  17. West Nile virus-induced cell adhesion molecules on human brain microvascular endothelial cells regulate leukocyte adhesion and modulate permeability of the in vitro blood-brain barrier model.

    Directory of Open Access Journals (Sweden)

    Kelsey Roe

    Full Text Available Characterizing the mechanisms by which West Nile virus (WNV causes blood-brain barrier (BBB disruption, leukocyte infiltration into the brain and neuroinflammation is important to understand the pathogenesis of WNV encephalitis. Here, we examined the role of endothelial cell adhesion molecules (CAMs in mediating the adhesion and transendothelial migration of leukocytes across human brain microvascular endothelial cells (HBMVE. Infection with WNV (NY99 strain significantly induced ICAM-1, VCAM-1, and E-selectin in human endothelial cells and infected mice brain, although the levels of their ligands on leukocytes (VLA-4, LFA-1and MAC-1 did not alter. The permeability of the in vitro BBB model increased dramatically following the transmigration of monocytes and lymphocytes across the models infected with WNV, which was reversed in the presence of a cocktail of blocking antibodies against ICAM-1, VCAM-1, and E-selectin. Further, WNV infection of HBMVE significantly increased leukocyte adhesion to the HBMVE monolayer and transmigration across the infected BBB model. The blockade of these CAMs reduced the adhesion and transmigration of leukocytes across the infected BBB model. Further, comparison of infection with highly neuroinvasive NY99 and non-lethal (Eg101 strain of WNV demonstrated similar level of virus replication and fold-increase of CAMs in HBMVE cells suggesting that the non-neuropathogenic response of Eg101 is not because of its inability to infect HBMVE cells. Collectively, these results suggest that increased expression of specific CAMs is a pathological event associated with WNV infection and may contribute to leukocyte infiltration and BBB disruption in vivo. Our data further implicate that strategies to block CAMs to reduce BBB disruption may limit neuroinflammation and virus-CNS entry via 'Trojan horse' route, and improve WNV disease outcome.

  18. Neutrophil adhesion and chemotaxis depend on substrate mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Jannat, Risat A; Hammer, Daniel A [Department of Bioengineering, University of Pennsylvania, 240 Skirkanich Hall, 210 South 33rd Street, Philadelphia, PA 19104 (United States); Robbins, Gregory P; Ricart, Brendon G [Department of Chemical and Biomolecular Engineering, University of Pennsylvania, 311A Towne Building, 220 South 33rd Street, Philadelphia, PA 19104 (United States); Dembo, Micah, E-mail: hammer@seas.upenn.ed [Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215 (United States)

    2010-05-19

    Neutrophil adhesion to the vasculature and chemotaxis within tissues play critical roles in the inflammatory response to injury and pathogens. Unregulated neutrophil activity has been implicated in the progression of numerous chronic and acute diseases such as rheumatoid arthritis, asthma and sepsis. Cell migration of anchorage-dependent cells is known to depend on both chemical and mechanical interactions. Although neutrophil responses to chemical cues have been well characterized, little is known about the effect of underlying tissue mechanics on neutrophil adhesion and migration. To address this question, we quantified neutrophil migration and traction stresses on compliant hydrogel substrates with varying elasticity in a micromachined gradient chamber in which we could apply either a uniform concentration or a precise gradient of the bacterial chemoattractant fMLP. Neutrophils spread more extensively on substrates of greater stiffness. In addition, increasing the stiffness of the substrate leads to a significant increase in the chemotactic index for each fMLP gradient tested. As the substrate becomes stiffer, neutrophils generate higher traction forces without significant changes in cell speed. These forces are often displayed in pairs and focused in the uropod. Increases in the mean fMLP concentration beyond the K{sub D} of the receptor lead to a decrease in chemotactic index on all surfaces. Blocking with an antibody against {beta}{sub 2}-integrins leads to a significant reduction, but not an elimination, of directed motility on stiff materials, but no change in motility on soft materials, suggesting neutrophils can display both integrin-dependent and integrin-independent motility. These findings are critical for understanding how neutrophil migration may change in different mechanical environments in vivo and can be used to guide the design of migration inhibitors that more efficiently target inflammation.

  19. Heme Oxygenase-1 Inhibits HLA Class I Antibody-Dependent Endothelial Cell Activation.

    Directory of Open Access Journals (Sweden)

    Eva Zilian

    Full Text Available Antibody-mediated rejection (AMR is a key limiting factor for long-term graft survival in solid organ transplantation. Human leukocyte antigen (HLA class I (HLA I antibodies (Abs play a major role in the pathogenesis of AMR via their interactions with HLA molecules on vascular endothelial cells (ECs. The antioxidant enzyme heme oxygenase (HO-1 has anti-inflammatory functions in the endothelium. As complement-independent effects of HLA I Abs can activate ECs, it was the goal of the current study to investigate the role of HO-1 on activation of human ECs by HLA I Abs. In cell cultures of various primary human macro- and microvascular ECs treatment with monoclonal pan- and allele-specific HLA I Abs up-regulated the expression of inducible proinflammatory adhesion molecules and chemokines (vascular cell adhesion molecule-1 [VCAM-1], intercellular cell adhesion molecule-1 [ICAM-1], interleukin-8 [IL-8] and monocyte chemotactic protein 1 [MCP-1]. Pharmacological induction of HO-1 with cobalt-protoporphyrin IX reduced, whereas inhibition of HO-1 with either zinc-protoporphyrin IX or siRNA-mediated knockdown increased HLA I Ab-dependent up-regulation of VCAM-1. Treatment with two carbon monoxide (CO-releasing molecules, which liberate the gaseous HO product CO, blocked HLA I Ab-dependent EC activation. Finally, in an in vitro adhesion assay exposure of ECs to HLA I Abs led to increased monocyte binding, which was counteracted by up-regulation of HO-1. In conclusion, HLA I Ab-dependent EC activation is modulated by endothelial HO-1 and targeted induction of this enzyme may be a novel therapeutic approach for the treatment of AMR in solid organ transplantation.

  20. Huhe Block

    Institute of Scientific and Technical Information of China (English)

    1996-01-01

    @@ Huhe Block is located in the mid-west part of Inner Mogolia Autonomous Region, covering an area of 15 079km2, in the range of 109°40'-112°00'E and 39°23()-40°40'N. Topographically. the Fengzhen hill is to the east, the Yinshan Mounts is to the north, the Hetao Plain and Ordos Plateau are respectively in its west and south.The Yellow River flows across this block. The elevation is 1 000 m in the flat area and in the range of 1 000-1 300m. in the plateau area, good for the development of agriculture and industry as well as husbandry. It belongs to inland plateau climate with annually averaged temperature of 8℃, the minimum being -12℃ in winter and the maximum 22℃ in summer.

  1. Reversible Thermoset Adhesives

    Science.gov (United States)

    Mac Murray, Benjamin C. (Inventor); Tong, Tat H. (Inventor); Hreha, Richard D. (Inventor)

    2016-01-01

    Embodiments of a reversible thermoset adhesive formed by incorporating thermally-reversible cross-linking units and a method for making the reversible thermoset adhesive are provided. One approach to formulating reversible thermoset adhesives includes incorporating dienes, such as furans, and dienophiles, such as maleimides, into a polymer network as reversible covalent cross-links using Diels Alder cross-link formation between the diene and dienophile. The chemical components may be selected based on their compatibility with adhesive chemistry as well as their ability to undergo controlled, reversible cross-linking chemistry.

  2. Electro-dry-adhesion.

    Science.gov (United States)

    Krahn, Jeffrey; Menon, Carlo

    2012-03-27

    This work presents novel conductive bioinspired dry adhesives with mushroom caps that enable the use of a synergistic combination of electrostatic and van der Waals forces (electro-dry-adhesion). An increase in shear adhesion bond strength of up to 2046% on a wide range of materials is measured when a maximum electrical field of 36.4 V μm(-1) is applied. A suction effect, due to the shape of the dry adhesive fibers, on overall adhesion was not noted for electro-dry-adhesives when testing was performed at both atmospheric and reduced pressure. Utilization of electrostatics to apply a preloading force to dry adhesive fiber arrays allows increased adhesion even after electrostatic force generation has been halted by ensuring the close contact necessary for van der Waals forces to be effective. A comparison is made between self-preloading of the electro-dry-adhesives and the direct application of a normal preloading pressure resulting in nearly the same shear bond strength with an applied voltage of 3.33 kV on the same sample.

  3. Polyelectrolytes Multilayers to Modulate Cell Adhesion: A Study of the Influence of Film Composition and Polyelectrolyte Interdigitation on the Adhesion of the A549 Cell Line.

    Science.gov (United States)

    Muzzio, Nicolás E; Pasquale, Miguel A; Gregurec, Danijela; Diamanti, Eleftheria; Kosutic, Marija; Azzaroni, Omar; Moya, Sergio E

    2016-04-01

    Polyelectrolyte multilayers (PEMs) with different polycation/polyanion pairs are fabricated by the layer-by-layer technique employing synthetic, natural, and both types of polyelectrolytes. The impact of the chemical composition of PEMs on cell adhesion is assessed by studying cell shape, spreading area, focal contacts, and cell proliferation for the A549 cell line. Cells exhibit good adhesion on PEMs containing natural polycations and poly(sodium 4-styrenesulfonate) (PSS) as polyanion, but limited adhesion is observed on PEMs fabricated from both natural polyelectrolytes. PEMs are then assembled, depositing a block of natural polyelectrolytes on top of a stiffer block with PSS as polyanion. Cell adhesion is enhanced on top of the diblock PEMs compared to purely natural PEMs. This fact could be explained by the interdigitation between polyelectrolytes from the two blocks. Diblock PEM assembly provides a simple means to tune cell adhesion on biocompatible PEMs. PMID:26663657

  4. Tissue adhesives in otorhinolaryngology

    Directory of Open Access Journals (Sweden)

    Schneider, Gerlind

    2009-01-01

    Full Text Available The development of medical tissue adhesives has a long history without finding an all-purpose tissue adhesive for clinical daily routine. This is caused by the specific demands which are made on a tissue adhesive, and the different areas of application. In otorhinolaryngology, on the one hand, this is the mucosal environment as well as the application on bones, cartilage and periphery nerves. On the other hand, there are stressed regions (skin, oral cavity, pharynx, oesophagus, trachea and unstressed regions (middle ear, nose and paranasal sinuses, cranial bones. But due to the facts that adhesives can have considerable advantages in assuring surgery results, prevention of complications and so reduction of medical costs/treatment expenses, the search for new adhesives for use in otorhinolaryngology will be continued intensively. In parallel, appropriate application systems have to be developed for microscopic and endoscopic use.

  5. Recurrent congenital heart block in neonatal lupus.

    Science.gov (United States)

    Escobar, Maria C; Gómez-Puerta, José A; Albert, Dimpna; Ferrer, Queralt; Girona, Josep

    2007-07-01

    Congenital heart block (CHB) is the main complication of neonatal lupus (NL) and is strongly associated with the presence of anti-SSA/Ro and anti-SSB/La antibodies. The recurrence of CHB in subsequent pregnancies in mothers with these antibodies is uncommon, occurring in approximately 15% of cases. We describe here a case of recurrent CHB in a previously asymptomatic mother with Sjögren syndrome and discuss the current strategies for the prevention and treatment of CHB in NL.

  6. Flavonoids inhibit cytokine-induced endothelial cell adhesion protein gene expression.

    OpenAIRE

    Gerritsen, M. E.; Carley, W. W.; Ranges, G. E.; Shen, C. P.; Phan, S. A.; Ligon, G. F.; Perry, C. A.

    1995-01-01

    Treatment of human endothelial cells with cytokines such as interleukin-1, tumor necrosis factor-alpha (TNF-alpha) or interferon-gamma induces the expression of specific leukocyte adhesion molecules on the endothelial cell surface. Interfering with either leukocyte adhesion or adhesion protein upregulation is an important therapeutic target as evidenced by the potent anti-inflammatory actions of neutralizing antibodies to these ligands in various animal models and in patients. In the present ...

  7. Antibody levels against GLURP R2, MSP1 block 2 hybrid and AS202.11 and the risk of malaria in children living in hyperendemic (Burkina Faso) and hypo-endemic (Ghana) areas

    DEFF Research Database (Denmark)

    Adu, Bright; Cherif, Mariama K; Bosomprah, Samuel;

    2016-01-01

    with increased risk of malaria (HR 1.29; 95 % CI 1.01-1.65, p = 0.04). CONCLUSION: These findings support further development of GLURP R2 and MSP1 block 2 hybrid, perhaps as a fusion vaccine antigen targeting malaria blood stage that can be deployed in areas of varying transmission intensity....

  8. Adhesion and Fusion of Muscle Cells Are Promoted by Filopodia.

    Science.gov (United States)

    Segal, Dagan; Dhanyasi, Nagaraju; Schejter, Eyal D; Shilo, Ben-Zion

    2016-08-01

    Indirect flight muscles (IFMs) in Drosophila are generated during pupariation by fusion of hundreds of myoblasts with larval muscle templates (myotubes). Live observation of these muscles during the fusion process revealed multiple long actin-based protrusions that emanate from the myotube surface and require Enabled and IRSp53 for their generation and maintenance. Fusion is blocked when formation of these filopodia is compromised. While filopodia are not required for the signaling process underlying critical myoblast cell-fate changes prior to fusion, myotube-myoblast adhesion appears to be filopodia dependent. Without filopodia, close apposition between the cell membranes is not achieved, the cell-adhesion molecule Duf is not recruited to the myotube surface, and adhesion-dependent actin foci do not form. We therefore propose that the filopodia are necessary to prime the heterotypic adhesion process between the two cell types, possibly by recruiting the cell-adhesion molecule Sns to discrete patches on the myoblast cell surface.

  9. Radiation results in IL-8 mediated intercellular signaling that increases adhesion between monocytic cells and aortic endothelium

    Science.gov (United States)

    Kucik, Dennis; Babitz, Stephen; Dunaway, Chad; Steele, Chad

    cells (HAECs) in vitro under conditions that mimic the shear stress in the bloodstream. For both heavy ions and x-rays, these adhesiveness changes are independent of adhesion molecule expression levels, but are chemokine dependent. Here we identify the specific endothelial chemokine responsible for this radiation-induced adhesiveness. X-irradiation increased IL-8 secretion almost 5-fold, while having little or no effect on expression of 15 other chemokines. Adhesiveness was then assayed under physiological shear stress using a flow chamber adhesion assay. Radiation significantly increased endothelial adhesiveness. The radiation-induced adhesiveness was specifically blocked by anti-IL-8 antibody, with no effect on baseline, radiation-independent adhesion. Addition of recombinant human IL-8 to un-irradiated HAECs was sufficient to increase adhesion to the same level as x-rays. Therefore, radiation-induced IL-8 signaling is both necessary and sufficient for radiation effects on aortic endothelial adhesiveness. This IL-8 induced adhesiveness may explain, at least in part, the mechanism by which radiation accelerates development of atherosclerosis. A better understanding of this mechanism can provide the basis for future countermeasure development.

  10. Handbook of adhesion

    CERN Document Server

    Packham, D E

    2006-01-01

    This second edition of the successful Handbook of Adhesion provides concise and authoritative articles covering many aspects of the science and technology associated with adhesion and adhesives. It is intended to fill a gap between the necessarily simplified treatment of the student textbook and the full and thorough treatment of the research monograph and review article. The articles are structured in such a way, with internal cross-referencing and external literature references, that the reader can build up a broader and deeper understanding, as their needs require.This second edition includ

  11. [Endothelial cell adhesion molecules].

    Science.gov (United States)

    Ivanov, A N; Norkin, I A; Puchin'ian, D M; Shirokov, V Iu; Zhdanova, O Iu

    2014-01-01

    The review presents current data concerning the functional role of endothelial cell adhesion molecules belonging to different structural families: integrins, selectins, cadherins, and the immunoglobulin super-family. In this manuscript the regulatory mechanisms and factors of adhesion molecules expression and distribution on the surface of endothelial cells are discussed. The data presented reveal the importance of adhesion molecules in the regulation of structural and functional state of endothelial cells in normal conditions and in pathology. Particular attention is paid to the importance of these molecules in the processes of physiological and pathological angiogenesis, regulation of permeability of the endothelial barrier and cell transmigration.

  12. Lactobacillus Adhesion to Mucus

    Directory of Open Access Journals (Sweden)

    Maxwell L. Van Tassell

    2011-05-01

    Full Text Available Mucus provides protective functions in the gastrointestinal tract and plays an important role in the adhesion of microorganisms to host surfaces. Mucin glycoproteins polymerize, forming a framework to which certain microbial populations can adhere, including probiotic Lactobacillus species. Numerous mechanisms for adhesion to mucus have been discovered in lactobacilli, including partially characterized mucus binding proteins. These mechanisms vary in importance with the in vitro models studied, which could significantly affect the perceived probiotic potential of the organisms. Understanding the nature of mucus-microbe interactions could be the key to elucidating the mechanisms of probiotic adhesion within the host.

  13. Cadherin-Based Intercellular Adhesions Organize Epithelial Cell-Matrix Traction Forces

    CERN Document Server

    Mertz, Aaron F; Banerjee, Shiladitya; Goldstein, Jill; Rosowski, Kathryn R; Niessen, Carien M; Marchetti, M Cristina; Dufresne, Eric R; Horsley, Valerie

    2012-01-01

    Cell--cell and cell-matrix adhesions play essential roles in the function of tissues. There is growing evidence for the importance of crosstalk between these two adhesion types, yet little is known about the impact of these interactions on the mechanical coupling of cells to the extracellular-matrix (ECM). Here, we combine experiment and theory to reveal how intercellular adhesions modulate forces transmitted to the ECM. In the absence of cadherin-based adhesions, primary mouse keratinocytes within a colony appear to act independently, with significant traction forces extending throughout the colony. In contrast, with strong cadherin-based adhesions, keratinocytes in a cohesive colony localize traction forces to the colony periphery. Through genetic or antibody-mediated loss of cadherin expression or function, we show that cadherin-based adhesions are essential for this mechanical cooperativity. A minimal physical model in which cell--cell adhesions modulate the physical cohesion between contractile cells is ...

  14. Decoding Cytoskeleton-Anchored and Non-Anchored Receptors from Single-Cell Adhesion Force Data.

    Science.gov (United States)

    Sariisik, Ediz; Popov, Cvetan; Müller, Jochen P; Docheva, Denitsa; Clausen-Schaumann, Hauke; Benoit, Martin

    2015-10-01

    Complementary to parameters established for cell-adhesion force curve analysis, we evaluated the slope before a force step together with the distance from the surface at which the step occurs and visualized the result in a two-dimensional density plot. This new tool allows detachment steps of long membrane tethers to be distinguished from shorter jumplike force steps, which are typical for cytoskeleton-anchored bonds. A prostate cancer cell line (PC3) immobilized on an atomic-force-microscopy sensor interacted with three different substrates: collagen-I (Col-I), bovine serum albumin, and a monolayer of bone marrow-derived stem cells (SCP1). To address PC3 cells' predominant Col-I binding molecules, an antibody-blocking β1-integrin was used. Untreated PC3 cells on Col-I or SCP1 cells, which express Col-I, predominantly showed jumps in their force curves, while PC3 cells on bovine-serum-albumin- and antibody-treated PC3 cells showed long membrane tethers. The probability density plots thus revealed that β1-integrin-specific interactions are predominately anchored to the cytoskeleton, while the nonspecific interactions are mainly membrane-anchored. Experiments with latrunculin-A-treated PC3 cells corroborated these observations. The plots thus reveal details of the anchoring of bonds to the cell and provide a better understanding of receptor-ligand interactions. PMID:26445433

  15. Leukocyte Adhesion Deficiency (LAD)

    Science.gov (United States)

    ... Content Marketing Share this: Main Content Area Leukocyte Adhesion Deficiency (LAD) LAD is an immune deficiency in ... are slow to heal also may have LAD. Treatment and Research Doctors prescribe antibiotics to prevent and ...

  16. Management of adhesive capsulitis

    OpenAIRE

    Neviaser, Andrew

    2015-01-01

    Kristen L Stupay,1 Andrew S Neviaser2 1Tulane University School of Medicine, New Orleans, LA, USA; 2George Washington University Medical Faculty Associates, Washington, DC, USA Abstract: Adhesive capsulitis of the shoulder is a condition of capsular contracture that reduces both active and passive glenohumeral motion. The cause of adhesive capsulitis is not known but it is strongly associated with endocrine abnormalities such as diabetes. Diverse terminology and the absence of definitive cri...

  17. Bioinspired pressure actuated adhesive system

    NARCIS (Netherlands)

    Paretkar, D.R.; Kamperman, M.M.G.; Schneider, A.S.; Martina, D.; Creton, C.; Arzt, E.

    2011-01-01

    We developed a dry synthetic adhesive system inspired by gecko feet adhesion that can switch reversibly from adhesion to non-adhesion with applied pressure as external stimulus. Micropatterned polydimethylsiloxane (PDMS) surfaces with pillars of 30 µm length and 10 µm diameter were fabricated using

  18. Specific inhibition of T-cell adhesion to extracellular matrix and proinflammatory cytokine secretion by human recombinant galectin-1.

    Science.gov (United States)

    Rabinovich, G A; Ariel, A; Hershkoviz, R; Hirabayashi, J; Kasai, K I; Lider, O

    1999-05-01

    The migration of immune cells through the extracellular matrix (ECM) towards inflammatory sites is co-ordinated by receptors recognizing ECM glycoproteins, chemokines and proinflammatory cytokines. In this context, galectins are secreted to the extracellular milieu, where they recognize poly-N-acetyllactosamine chains on major ECM glycoproteins, such as fibronectin and laminin. We investigated the possibility that galectin-1 could modulate the adhesion of human T cells to ECM and ECM components. T cells were purified from human blood, activated with interleukin-2 (IL-2), labelled, and incubated further with intact immobilized ECM and ECM glycoproteins in the presence of increasing concentrations of human recombinant galectin-1, or its more stable, related, C2-S molecule obtained by site-directed mutagenesis. The presence of galectin-1 was shown to inhibit T-cell adhesion to intact ECM, laminin and fibronectin, and to a lesser extent to collagen type IV, in a dose-dependent manner. This effect was specifically blocked by anti-galectin-1 antibody and was dependent on the lectin's carbohydrate-binding properties. The inhibition of T-cell adhesion by galectin-1 correlates with the ability of this molecule to block the re-organization of the activated cell's actin cytoskeleton. Furthermore, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) production was markedly reduced when IL-2-activated T cells were incubated with galectin-1 or its mutant. This effect was prevented by beta-galactoside-related sugars. The present study reveals an alternative inhibitory mechanism for explaining the suppressive properties of the galectin-1 subfamily on inflammatory and autoimmune processes. PMID:10447720

  19. Dry adhesives with sensing features

    Science.gov (United States)

    Krahn, J.; Menon, C.

    2013-08-01

    Geckos are capable of detecting detachment of their feet. Inspired by this basic observation, a novel functional dry adhesive is proposed, which can be used to measure the instantaneous forces and torques acting on an adhesive pad. Such a novel sensing dry adhesive could potentially be used by climbing robots to quickly realize and respond appropriately to catastrophic detachment conditions. The proposed torque and force sensing dry adhesive was fabricated by mixing Carbon Black (CB) and Polydimethylsiloxane (PDMS) to form a functionalized adhesive with mushroom caps. The addition of CB to PDMS resulted in conductive PDMS which, when under compression, tension or torque, resulted in a change in the resistance across the adhesive patch terminals. The proposed design of the functionalized dry adhesive enables distinguishing an applied torque from a compressive force in a single adhesive pad. A model based on beam theory was used to predict the change in resistance across the terminals as either a torque or compressive force was applied to the adhesive patch. Under a compressive force, the sensing dry adhesive was capable of measuring compression stresses from 0.11 Pa to 20.9 kPa. The torque measured by the adhesive patch ranged from 2.6 to 10 mN m, at which point the dry adhesives became detached. The adhesive strength was 1.75 kPa under an applied preload of 1.65 kPa for an adhesive patch with an adhesive contact area of 7.07 cm2.

  20. Magnetic field switchable dry adhesives.

    Science.gov (United States)

    Krahn, Jeffrey; Bovero, Enrico; Menon, Carlo

    2015-02-01

    A magnetic field controllable dry adhesive device is manufactured. The normal adhesion force can be increased or decreased depending on the presence of an applied magnetic field. If the magnetic field is present during the entire normal adhesion test cycle which includes both applying a preloading force and measuring the pulloff pressure, a decrease in adhesion is observed when compared to when there is no applied magnetic field. Similarly, if the magnetic field is present only during the preload portion of the normal adhesion test cycle, a decrease in adhesion is observed because of an increased stiffness of the magnetically controlled dry adhesive device. When the applied magnetic field is present during only the pulloff portion of the normal adhesion test cycle, either an increase or a decrease in normal adhesion is observed depending on the direction of the applied magnetic field.

  1. Ultrasound guided supraclavicular block.

    LENUS (Irish Health Repository)

    Hanumanthaiah, Deepak

    2013-09-01

    Ultrasound guided regional anaesthesia is becoming increasingly popular. The supraclavicular block has been transformed by ultrasound guidance into a potentially safe superficial block. We reviewed the techniques of performing supraclavicular block with special focus on ultrasound guidance.

  2. Adhesion in hydrogel contacts

    Science.gov (United States)

    Torres, J. R.; Jay, G. D.; Kim, K.-S.; Bothun, G. D.

    2016-05-01

    A generalized thermomechanical model for adhesion was developed to elucidate the mechanisms of dissipation within the viscoelastic bulk of a hyperelastic hydrogel. Results show that in addition to the expected energy release rate of interface formation, as well as the viscous flow dissipation, the bulk composition exhibits dissipation due to phase inhomogeneity morphological changes. The mixing thermodynamics of the matrix and solvent determines the dynamics of the phase inhomogeneities, which can enhance or disrupt adhesion. The model also accounts for the time-dependent behaviour. A parameter is proposed to discern the dominant dissipation mechanism in hydrogel contact detachment.

  3. Switchable Adhesion in Vacuum Using Bio-Inspired Dry Adhesives

    OpenAIRE

    Purtov, Julia; Frensemeier, Mareike; Kroner, Elmar

    2015-01-01

    Suction based attachment systems for pick and place handling of fragile objects like glass plates or optical lenses are energy-consuming and noisy and fail at reduced air pressure, which is essential, e.g., in chemical and physical vapor deposition processes. Recently, an alternative approach toward reversible adhesion of sensitive objects based on bioinspired dry adhesive structures has emerged. There, the switching in adhesion is achieved by a reversible buckling of adhesive pillar structur...

  4. CADM1 controls actin cytoskeleton assembly and regulates extracellular matrix adhesion in human mast cells.

    Directory of Open Access Journals (Sweden)

    Elena P Moiseeva

    Full Text Available CADM1 is a major receptor for the adhesion of mast cells (MCs to fibroblasts, human airway smooth muscle cells (HASMCs and neurons. It also regulates E-cadherin and alpha6beta4 integrin in other cell types. Here we investigated a role for CADM1 in MC adhesion to both cells and extracellular matrix (ECM. Downregulation of CADM1 in the human MC line HMC-1 resulted not only in reduced adhesion to HASMCs, but also reduced adhesion to their ECM. Time-course studies in the presence of EDTA to inhibit integrins demonstrated that CADM1 provided fast initial adhesion to HASMCs and assisted with slower adhesion to ECM. CADM1 downregulation, but not antibody-dependent CADM1 inhibition, reduced MC adhesion to ECM, suggesting indirect regulation of ECM adhesion. To investigate potential mechanisms, phosphotyrosine signalling and polymerisation of actin filaments, essential for integrin-mediated adhesion, were examined. Modulation of CADM1 expression positively correlated with surface KIT levels and polymerisation of cortical F-actin in HMC-1 cells. It also influenced phosphotyrosine signalling and KIT tyrosine autophosphorylation. CADM1 accounted for 46% of surface KIT levels and 31% of F-actin in HMC-1 cells. CADM1 downregulation resulted in elongation of cortical actin filaments in both HMC-1 cells and human lung MCs and increased cell rigidity of HMC-1 cells. Collectively these data suggest that CADM1 is a key adhesion receptor, which regulates MC net adhesion, both directly through CADM1-dependent adhesion, and indirectly through the regulation of other adhesion receptors. The latter is likely to occur via docking of KIT and polymerisation of cortical F-actin. Here we propose a stepwise model of adhesion with CADM1 as a driving force for net MC adhesion.

  5. Modulation of cell adhesion and migration by the histone methyltransferase subunit mDpy-30 and its interacting proteins.

    Directory of Open Access Journals (Sweden)

    Bin Xia

    Full Text Available We have previously shown that a subset of mDpy-30, an accessory subunit of the nuclear histone H3 lysine 4 methyltransferase (H3K4MT complex, also localizes at the trans-Golgi network (TGN, where its recruitment is mediated by the TGN-localized ARF guanine nucleotide exchange factor (ArfGEF BIG1. Depletion of mDpy-30 inhibits the endosome-to-TGN transport of internalized CIMPR receptors and concurrently promotes their accumulation at the cell protrusion. These observations suggest mDpy-30 may play a novel role at the crossroads of endosomal trafficking, nuclear transcription and adhesion/migration. Here we provide novel mechanistic and functional insight into this association. First, we demonstrate a direct interaction between mDpy-30 and BIG1 and locate the binding region in the N-terminus of BIG1. Second, we provide evidence that the depletion or overexpression of mDpy-30 enhances or inhibits cellular adhesion/migration of glioma cells in vitro, respectively. A similar increase in cell adhesion/migration is observed in cells with reduced levels of BIG1 or other H3K4MT subunits. Third, knockdown of mDpy-30, BIG1, or the RbBP5 H3K4MT subunit increases the targeting of beta1 integrin to cell protrusions, and suppression of H3K4MT activity by depleting mDpy-30 or RbBP5 leads to increased protein and mRNA levels of beta1 integrin. Moreover, stimulation of cell adhesion/migration via mDpy-30 knockdown is abolished after treating cells with a function-blocking antibody to beta1 integrin. Taken together, these data indicate that mDpy-30 and its interacting proteins function as a novel class of cellular adhesion/migration modulators partially by affecting the subcellular distribution of endosomal compartments as well as the expression of key adhesion/migration proteins such as beta1 integrin.

  6. Switchable Adhesion in Vacuum Using Bio-Inspired Dry Adhesives.

    Science.gov (United States)

    Purtov, Julia; Frensemeier, Mareike; Kroner, Elmar

    2015-11-01

    Suction based attachment systems for pick and place handling of fragile objects like glass plates or optical lenses are energy-consuming and noisy and fail at reduced air pressure, which is essential, e.g., in chemical and physical vapor deposition processes. Recently, an alternative approach toward reversible adhesion of sensitive objects based on bioinspired dry adhesive structures has emerged. There, the switching in adhesion is achieved by a reversible buckling of adhesive pillar structures. In this study, we demonstrate that these adhesives are capable of switching adhesion not only in ambient air conditions but also in vacuum. Our bioinspired patterned adhesive with an area of 1 cm(2) provided an adhesion force of 2.6 N ± 0.2 N in air, which was reduced to 1.9 N ± 0.2 N if measured in vacuum. Detachment was induced by buckling of the structures due to a high compressive preload and occurred, independent of air pressure, at approximately 0.9 N ± 0.1 N. The switch in adhesion was observed at a compressive preload between 5.6 and 6.0 N and was independent of air pressure. The difference between maximum adhesion force and adhesion force after buckling gives a reasonable window of operation for pick and place processes. High reversibility of the switching behavior is shown over 50 cycles in air and in vacuum, making the bioinspired switchable adhesive applicable for handling operations of fragile objects. PMID:26457864

  7. Switchable Adhesion in Vacuum Using Bio-Inspired Dry Adhesives.

    Science.gov (United States)

    Purtov, Julia; Frensemeier, Mareike; Kroner, Elmar

    2015-11-01

    Suction based attachment systems for pick and place handling of fragile objects like glass plates or optical lenses are energy-consuming and noisy and fail at reduced air pressure, which is essential, e.g., in chemical and physical vapor deposition processes. Recently, an alternative approach toward reversible adhesion of sensitive objects based on bioinspired dry adhesive structures has emerged. There, the switching in adhesion is achieved by a reversible buckling of adhesive pillar structures. In this study, we demonstrate that these adhesives are capable of switching adhesion not only in ambient air conditions but also in vacuum. Our bioinspired patterned adhesive with an area of 1 cm(2) provided an adhesion force of 2.6 N ± 0.2 N in air, which was reduced to 1.9 N ± 0.2 N if measured in vacuum. Detachment was induced by buckling of the structures due to a high compressive preload and occurred, independent of air pressure, at approximately 0.9 N ± 0.1 N. The switch in adhesion was observed at a compressive preload between 5.6 and 6.0 N and was independent of air pressure. The difference between maximum adhesion force and adhesion force after buckling gives a reasonable window of operation for pick and place processes. High reversibility of the switching behavior is shown over 50 cycles in air and in vacuum, making the bioinspired switchable adhesive applicable for handling operations of fragile objects.

  8. Monoclonal antibodies

    International Nuclear Information System (INIS)

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

  9. Amine-functionalized polypyrrole: Inherently cell adhesive conducting polymer.

    Science.gov (United States)

    Lee, Jae Y; Schmidt, Christine E

    2015-06-01

    Electrically conducting polymers (CPs) have been recognized as novel biomaterials that can electrically communicate with biological systems. For their tissue engineering applications, CPs have been modified to promote cell adhesion for improved interactions between biomaterials and cells/tissues. Conventional approaches to improve cell adhesion involve the surface modification of CPs with biomolecules, such as physical adsorption of cell adhesive proteins and polycationic polymers, or their chemical immobilization; however, these approaches require additional multiple modification steps with expensive biomolecules. In this study, as a simple and effective alternative to such additional biomolecule treatment, we synthesized amine-functionalized polypyrrole (APPy) that inherently presents cell adhesion-supporting positive charges under physiological conditions. The synthesized APPy provides electrical activity in a moderate range and a hydrophilic surface compared to regular polypyrrole (PPy) homopolymers. Under both serum and serum-free conditions, APPy exhibited superior attachment of human dermal fibroblasts and Schwann cells compared to PPy homopolymer controls. Moreover, Schwann cell adhesion onto the APPy copolymer was at least similar to that on poly-l-lysine treated PPy controls. Our results indicate that amine-functionalized CP substrates will be useful to achieve good cell adhesion and potentially electrically stimulate various cells. In addition, amine functionality present on CPs can further serve as a novel and flexible platform to chemically tether various bioactive molecules, such as growth factors, antibodies, and chemical drugs. PMID:25294089

  10. Pathogenesis of postoperative adhesion formation

    NARCIS (Netherlands)

    Hellebrekers, B.W.J.; Kooistra, T.

    2011-01-01

    Background: Current views on the pathogenesis of adhesion formation are based on the "classical concept of adhesion formation", namely that a reduction in peritoneal fibrinolytic activity following peritoneal trauma is of key importance in adhesion development. Methods: A non-systematic literature s

  11. Creative Construction: Unit Blocks.

    Science.gov (United States)

    Texas Child Care, 1999

    1999-01-01

    Describes the use of unit blocks with young children in early childhood education (ECE) settings to expand all areas of the curriculum. Discusses the origin of blocks in ECE programs, presents developmental stages of block play, describes children's building styles, and makes recommendations for getting started in block play for children of…

  12. Monoclonal antibodies.

    Science.gov (United States)

    2009-01-01

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

  13. Antibody-mediated immune suppression is improved when blends of anti-RBC monoclonal antibodies are used in mice.

    Science.gov (United States)

    Bernardo, Lidice; Amash, Alaa; Marjoram, Danielle; Lazarus, Alan H

    2016-08-25

    Although the prevention of hemolytic disease of the fetus and newborn is highly effective using polyclonal anti-D, a recombinant alternative is long overdue. Unfortunately, anti-D monoclonal antibodies have been, at best, disappointing. To determine the primary attribute defining an optimal antibody, we assessed suppression of murine red blood cell (RBC) immunization by single-monoclonal antibodies vs defined blends of subtype-matched antibodies. Allogeneic RBCs expressing the HOD antigen (hen egg lysozyme [HEL]-ovalbumin-human transmembrane Duffy(b)) were transfused into naïve mice alone or together with selected combinations of HEL-specific antibodies, and the resulting suppressive effect was assessed by evaluating the antibody response. Polyclonal HEL antibodies dramatically inhibited the antibody response to the HOD antigen, whereas single-monoclonal HEL antibodies were less effective despite the use of saturating doses. A blend of monoclonal HEL-specific antibodies reactive with different HEL epitopes significantly increased the suppressive effect, whereas a blend of monoclonal antibodies that block each other's binding to the HEL protein did not increase suppression. In conclusion, these data show that polyclonal antibodies are superior to monoclonal antibodies at suppressing the immune response to the HOD cells, a feature that can be completely recapitulated using monoclonal antibodies to different epitopes. PMID:27330002

  14. Antibody and B cell responses to Plasmodium sporozoites

    Directory of Open Access Journals (Sweden)

    Johanna N Dups

    2014-11-01

    Full Text Available Antibodies are capable of blocking infection of the liver by Plasmodium sporozoites. Accordingly the induction of anti-sporozoite antibodies is a major aim of various vaccine approaches to malaria. In recent years our knowledge of the specificity and quantities of antibodies required for protection has been greatly expanded by clinical trials of various whole sporozoite and subunit vaccines. Moreover, the development of humanized mouse models and transgenic parasites have also aided our ability to assess the specificity of antibodies and their ability to block infection. Nonetheless, considerable gaps remain in our knowledge - in particular in understanding what antigens are recognized by infection blocking antibodies and in knowing how we can induce robust, long-lived antibody responses. Maintaining high levels of circulating antibodies is likely to be of primary importance, as antibodies must block infection in the short time it takes for sporozoites to reach the liver from the skin. It is clear that a better understanding of the development of protective B cell-mediated immunity will aid the development and refinement of malaria vaccines.

  15. Management of adhesive capsulitis

    Directory of Open Access Journals (Sweden)

    Stupay KL

    2015-08-01

    Full Text Available Kristen L Stupay,1 Andrew S Neviaser2 1Tulane University School of Medicine, New Orleans, LA, USA; 2George Washington University Medical Faculty Associates, Washington, DC, USA Abstract: Adhesive capsulitis of the shoulder is a condition of capsular contracture that reduces both active and passive glenohumeral motion. The cause of adhesive capsulitis is not known but it is strongly associated with endocrine abnormalities such as diabetes. Diverse terminology and the absence of definitive criteria for diagnosis make evaluating treatment modalities difficult. Many treatment methods have been reported, most with some success, but few have been proved to alter the natural course of this disease. Most afflicted patients will achieve acceptable shoulder function without surgery. Those who remain debilitated after 8–12 months are reasonable candidates for invasive treatments. Here, the various treatment methods and the data to support their use are reviewed. Keywords: frozen shoulder, stiff shoulder, periarthritis, painful shoulder 

  16. Syndecans and cell adhesion

    DEFF Research Database (Denmark)

    Couchman, J R; Chen, L; Woods, A

    2001-01-01

    Now that transmembrane signaling through primary cell-matrix receptors, integrins, is being elucidated, attention is turning to how integrin-ligand interactions can be modulated. Syndecans are transmembrane proteoglycans implicated as coreceptors in a variety of physiological processes, including...... cell adhesion, migration, response to growth factors, development, and tumorigenesis. This review will describe this family of proteoglycans in terms of their structures and functions and their signaling in conjunction with integrins, and indicate areas for future research....

  17. CD13 is a novel mediator of monocytic/endothelial cell adhesion

    DEFF Research Database (Denmark)

    Mina-Osorio, Paola; Winnicka, Beata; O'Conor, Catherine;

    2008-01-01

    rearrangement and filopodia formation. Treatment with soluble recombinant (r)CD13 blocks this CD13-dependent adhesion, and CD13 molecules from monocytic and endothelial cells are present in the same immunocomplex, suggesting a direct participation of CD13 in the adhesive interaction. This concept......During inflammation, cell surface adhesion molecules guide the adhesion and migration of circulating leukocytes across the endothelial cells lining the blood vessels to access the site of injury. The transmembrane molecule CD13 is expressed on monocytes and endothelial cells and has been shown...... to mediate homotypic cell adhesion, which may imply a role for CD13 in inflammatory monocyte trafficking. Here, we show that ligation and clustering of CD13 by mAb or viral ligands potently induce myeloid cell/endothelial adhesion in a signal transduction-dependent manner involving monocytic cytoskeletal...

  18. TLR4-mediated expression of Mac-1 in monocytes plays a pivotal role in monocyte adhesion to vascular endothelium.

    Science.gov (United States)

    Lee, Seung Jin; Choi, Eun Kyoung; Seo, Kyo Won; Bae, Jin Ung; Park, So Youn; Kim, Chi Dae

    2014-01-01

    Toll-like receptor 4 (TLR4) is known to mediate monocyte adhesion to endothelial cells, however, its role on the expression of monocyte adhesion molecules is unclear. In the present study, we investigated the role of TLR4 on the expression of monocyte adhesion molecules, and determined the functional role of TLR4-induced adhesion molecules on monocyte adhesion to endothelial cells. When THP-1 monocytes were stimulated with Kdo2-Lipid A (KLA), a specific TLR4 agonist, Mac-1 expression was markedly increased in association with an increased adhesion of monocytes to endothelial cells. These were attenuated by anti-Mac-1 antibody, suggesting a functional role of TLR4-induced Mac-1 on monocyte adhesion to endothelial cells. In monocytes treated with MK886, a 5-lipoxygenase (LO) inhibitor, both Mac-1 expression and monocyte adhesion to endothelial cells induced by KLA were markedly attenuated. Moreover, KLA increased the expression of mRNA and protein of 5-LO, suggesting a pivotal role of 5-LO on these processes. In in vivo studies, KLA increased monocyte adhesion to aortic endothelium of wild-type (WT) mice, which was attenuated in WT mice treated with anti-Mac-1 antibody as well as in TLR4-deficient mice. Taken together, TLR4-mediated expression of Mac-1 in monocytes plays a pivotal role on monocyte adhesion to vascular endothelium, leading to increased foam cell formation in the development of atherosclerosis.

  19. Expression and function of neural cell adhesion molecule during limb regeneration.

    OpenAIRE

    Maier, C E; Watanabe, M.(Niigata University, 950-2181, Niigata, Japan); Singer, M.; McQuarrie, I G; Sunshine, J.; Rutishauser, U.

    1986-01-01

    The neural cell adhesion molecule (NCAM) has been detected in regenerating limb bud of adult newts in addition to brain and peripheral nerves. In the regenerating tissue, NCAM was found primarily on mesenchymal cells and also in wound epidermis. Infusion of Fab fragments of antibodies to NCAM into limb buds at the early blastema stage delayed the regenerative process. Previous studies have indicated that NCAM serves as a homophilic ligand for adhesion among cells that express this molecule an...

  20. A New Cell Block Method for Multiple Immunohistochemical Analysis of Circulating Tumor Cells in Patients with Liver Cancer

    Science.gov (United States)

    Nam, Soo Jeong; Yeo, Hyun Yang; Chang, Hee Jin; Kim, Bo Hyun; Hong, Eun Kyung; Park, Joong-Won

    2016-01-01

    Purpose We developed a new method of detecting circulating tumor cells (CTCs) in liver cancer patients by constructing cell blocks from peripheral blood cells, including CTCs, followed by multiple immunohistochemical analysis. Materials and Methods Cell blockswere constructed from the nucleated cell pellets of peripheral blood afterremoval of red blood cells. The blood cell blocks were obtained from 29 patients with liver cancer, and from healthy donor blood spikedwith seven cell lines. The cell blocks and corresponding tumor tissues were immunostained with antibodies to seven markers: cytokeratin (CK), epithelial cell adhesion molecule (EpCAM), epithelial membrane antigen (EMA), CK18, α-fetoprotein (AFP), Glypican 3, and HepPar1. Results The average recovery rate of spiked SW620 cells from blood cell blocks was 91%. CTCs were detected in 14 out of 29 patients (48.3%); 11/23 hepatocellular carcinomas (HCC), 1/2 cholangiocarcinomas (CC), 1/1 combined HCC-CC, and 1/3 metastatic cancers. CTCs from 14 patients were positive for EpCAM (57.1%), EMA (42.9%), AFP (21.4%), CK18 (14.3%), Gypican3 and CK (7.1%, each), and HepPar1 (0%). Patients with HCC expressed EpCAM, EMA, CK18, and AFP in tissue and/or CTCs, whereas CK, HepPar1, and Glypican3 were expressed only in tissue. Only EMA was significantly associated with the expressions in CTC and tissue. CTC detection was associated with higher T stage and portal vein invasion in HCC patients. Conclusion This cell block method allows cytologic detection and multiple immunohistochemical analysis of CTCs. Our results show that tissue biomarkers of HCC may not be useful for the detection of CTC. EpCAM could be a candidate marker for CTCs in patients with HCC. PMID:27034142

  1. Antibody to E- and L-selectin does not prevent lung injury or mortality in septic baboons.

    Science.gov (United States)

    Carraway, M S; Welty-Wolf, K E; Kantrow, S P; Huang, Y C; Simonson, S G; Que, L G; Kishimoto, T K; Piantadosi, C A

    1998-03-01

    Recruitment of polymorphonuclear leukocytes (PMN) through upregulation of cellular adhesion molecules is a proposed mechanism of injury in sepsis and acute respiratory distress syndrome (ARDS). We hypothesized that pretreatment of baboons with a monoclonal antibody to human E- and L-selectin (EL-246) during sepsis would decrease PMN influx into tissues and result in less organ injury during gram-negative sepsis. We studied 14 anesthetized, ventilated adult baboons; six animals received 1 mg/kg of EL-246 before infusion of an LD100 of live Escherichia coli and six received the E. coli infusion without antibody therapy. Two other animals received 1 mg/kg of EL-246 intravenously without an infusion of bacteria. Intermittent measurements were made of circulatory pressures, cardiac output, urine output, arterial blood gases, ventilation:perfusion ratio (VA/Q), and hematologic status. The experiments were ended at 48 h or at the time of death. Tissues were harvested for pathology and biochemical measurements. The E. coli infusions were associated with a hyperdynamic state, pulmonary hypertension, systemic hypotension, decreased urine output (UOP), and metabolic acidosis. The antibody partly blocked PMN migration, but there were few significant physiologic or biochemical differences between the EL-246-treated and untreated animals. In the antibody-treated animals, UOP was decreased, metabolic acidosis was worsened, and median survival time was decreased significantly. We conclude that treatment with an antibody to E- and L-selectin in gram-negative sepsis does not improve gas exchange or protect against lung injury, and is associated with decreased survival time in primates.

  2. [Antinuclear antibodies].

    Science.gov (United States)

    Cabiedes, Javier; Núñez-Álvarez, Carlos A

    2010-01-01

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

  3. ADAM2 interactions with mouse eggs and cell lines expressing α4/α9 (ITGA4/ITGA9 integrins: implications for integrin-based adhesion and fertilization.

    Directory of Open Access Journals (Sweden)

    Ulyana V Desiderio

    Full Text Available BACKGROUND: Integrins are heterodimeric cell adhesion molecules, with 18 α (ITGA and eight β (ITGB subunits forming 24 heterodimers classified into five families. Certain integrins, especially the α(4/α(9 (ITGA4/ITGA9 family, interact with members of the ADAM (a disintegrin and metalloprotease family. ADAM2 is among the better characterized and also of interest because of its role in sperm function. Having shown that ITGA9 on mouse eggs participates in mouse sperm-egg interactions, we sought to characterize ITGA4/ITGA9-ADAM2 interactions. METHODOLOGY/PRINCIPAL FINDINGS: An anti-β(1/ITGB1 function-blocking antibody that reduces sperm-egg binding significantly inhibited ADAM2 binding to mouse eggs. Analysis of integrin subunit expression indicates that mouse eggs could express at least ten different integrins, five in the RGD-binding family, two in the laminin-binding family, two in the collagen-binding family, and ITGA9-ITGB1. Adhesion assays to characterize ADAM2 interactions with ITGA4/ITGA9 family members produced the surprising result that RPMI 8866 cell adhesion to ADAM2 was inhibited by an anti-ITGA9 antibody, noteworthy because ITGA9 has only been reported to dimerize with ITGB1, and RPMI 8866 cells lack detectable ITGB1. Antibody and siRNA studies demonstrate that ITGB7 is the β subunit contributing to RPMI 8866 adhesion to ADAM2. CONCLUSIONS/SIGNIFICANCE: These data indicate that a novel integrin α-β combination, ITGA9-ITGB7 (α(9β(7, in RPMI 8866 cells functions as a binding partner for ADAM2. ITGA9 had previously only been reported to dimerize with ITGB1. Although ITGA9-ITGB7 is unlikely to be a widely expressed integrin and appears to be the result of "compensatory dimerization" occurring in the context of little/no ITGB1 expression, the data indicate that ITGA9-ITGB7 functions as an ADAM binding partner in certain cellular contexts, with implications for mammalian fertilization and integrin function.

  4. Molecular cloning and chemical synthesis of a region of platelet glycoprotein IIb involved in adhesive function.

    OpenAIRE

    Loftus, J C; Plow, E F; Frelinger, A.L.; D'Souza, S E; Dixon, D; Lacy, J.; Sorge, J; Ginsberg, M H

    1987-01-01

    Membrane glycoprotein (GP) IIb-IIIa is a component of a platelet adhesive protein receptor. A region of the heavy chain of GPIIb, defined by the monoclonal antibody PMI-1, is involved in adhesion receptor function. We have localized and chemically synthesized this region of GPIIb. A cDNA clone that directs the synthesis of a fusion protein reactive with the PMI-1 antibody was isolated from a phage lambda gt11 expression library constructed with mRNA from an erythroleukemia (HEL) cell line. Th...

  5. A feasibility study of using two-component polyurethane adhesive in constructing wooden structures

    Institute of Scientific and Technical Information of China (English)

    Mohammad Derikvand; Ghanbar Ebrahimi; Mehdi Tajvidi

    2014-01-01

    This investigation was conducted to determine the feasibility of using a two-component polyurethane (PUR) adhesive, with special waterproof properties, in constructing wooden structures. We designed and conducted tests to compare the shear strength and adhesion per-formance of PUR with polyvinyl acetate (PVAc) adhesive on block-shear specimens constructed of oriental beech (Fagus orientalis L.), fir (Abies alba Mill.), poplar (Populus deltoides Bartr.), white oak (Quercus alba L.), sycamore (Platanus orientalis L.) and white walnut (Juglans cinerea L.). The values of the percentage of wood failure were also determined in specimens constructed with each adhesive. The highest shear strength values of both adhesives were obtained in specimens constructed of beech, while the lowest shear strength values were obtained in fir and poplar specimens. Average shear strength of the PUR adhesive was 16.5%higher than that of the PVAc adhesive. Specimens constructed of fir, poplar and sycamore were characterised by the highest percentages of wood failure, whereas the lowest average percentages of wood failure were obtained in beech and oak specimens. With the exception of oak specimens, there was no statistically significant difference between per-centage of wood failure among the PUR and PVAc adhesives. Generally, the PUR adhesive showed an acceptable adhesion performance on wood materials used in our study.

  6. Isolation and Characterization of Adhesive Secretion from Cuvierian Tubules of Sea Cucumber Holothuria forskåli (Echinodermata: Holothuroidea

    Directory of Open Access Journals (Sweden)

    Malgorzata Baranowska

    2011-01-01

    Full Text Available The sea cucumber Holothuria forskåli possesses a specialized system called Cuvierian tubules. During mechanical stimulation white filaments (tubules are expelled and become sticky upon contact with any object. We isolated a protein with adhesive properties from protein extracts of Cuvierian tubules from H. forskåli. This protein was identified by antibodies against recombinant precollagen D which is located in the byssal threads of the mussel Mytilus galloprovincialis. To find out the optimal procedure for extraction and purification, the identified protein was isolated by several methods, including electroelution, binding to glass beads, immunoprecipitation, and gel filtration. Antibodies raised against the isolated protein were used for localization of the adhesive protein in Cuvierian tubules. Immunostaining and immunogold electron microscopical studies revealed the strongest immunoreactivity in the mesothelium; this tissue layer is involved in adhesion. Adhesion of Cuvierian tubule extracts was measured on the surface of various materials. The extracted protein showed the strongest adhesion to Teflon surface. Increased adhesion was observed in the presence of potassium and EDTA, while cadmium caused a decrease in adhesion. Addition of antibodies and trypsin abolished the adhesive properties of the extract.

  7. Amygdalin influences bladder cancer cell adhesion and invasion in vitro.

    Directory of Open Access Journals (Sweden)

    Jasmina Makarević

    Full Text Available The cyanogenic diglucoside amygdalin, derived from Rosaceae kernels, is employed by many patients as an alternative anti-cancer treatment. However, whether amygdalin indeed acts as an anti-tumor agent is not clear. Metastasis blocking properties of amygdalin on bladder cancer cell lines was, therefore, investigated. Amygdalin (10 mg/ml was applied to UMUC-3, TCCSUP or RT112 bladder cancer cells for 24 h or for 2 weeks. Tumor cell adhesion to vascular endothelium or to immobilized collagen as well as tumor cell migration was examined. Effects of drug treatment on integrin α and β subtypes, on integrin-linked kinase (ILK and total and activated focal adhesion kinase (FAK were also determined. Integrin knock-down was carried out to evaluate integrin influence on migration and adhesion. A 24 h or 2 week amygdalin application distinctly reduced tumor cell adhesion and migration of UMUC-3 and RT112 cells. TCCSUP adhesion was also reduced, but migration was elevated under amygdalin. Integrin subtype expression was significantly and specifically altered by amygdalin depending on the cell line. ILK was moderately, and activated FAK strongly, lost in all tumor cell lines in the presence of amygdalin. Knock down of β1 integrin caused a significant decrease in both adhesion and migration of UMUC-3 cells, but a significant increase in TCCSUP adhesion. Knock down of β4 integrin caused a significant decrease in migration of RT112 cells. Since the different actions of amygdalin on the different cell lines was mirrored by β1 or β4 knock down, it is postulated that amygdalin influences adhesion and migratory properties of bladder cancer cells by modulating β1 or β4 integrin expression. The amygdalin induced increase in TCCSUP migratory behavior indicates that any anti-tumor benefits from amygdalin (seen with the other two cell lines may depend upon the cancer cell type.

  8. Single cell adhesion assay using computer controlled micropipette.

    Directory of Open Access Journals (Sweden)

    Rita Salánki

    Full Text Available Cell adhesion is a fundamental phenomenon vital for all multicellular organisms. Recognition of and adhesion to specific macromolecules is a crucial task of leukocytes to initiate the immune response. To gain statistically reliable information of cell adhesion, large numbers of cells should be measured. However, direct measurement of the adhesion force of single cells is still challenging and today's techniques typically have an extremely low throughput (5-10 cells per day. Here, we introduce a computer controlled micropipette mounted onto a normal inverted microscope for probing single cell interactions with specific macromolecules. We calculated the estimated hydrodynamic lifting force acting on target cells by the numerical simulation of the flow at the micropipette tip. The adhesion force of surface attached cells could be accurately probed by repeating the pick-up process with increasing vacuum applied in the pipette positioned above the cell under investigation. Using the introduced methodology hundreds of cells adhered to specific macromolecules were measured one by one in a relatively short period of time (∼30 min. We blocked nonspecific cell adhesion by the protein non-adhesive PLL-g-PEG polymer. We found that human primary monocytes are less adherent to fibrinogen than their in vitro differentiated descendants: macrophages and dendritic cells, the latter producing the highest average adhesion force. Validation of the here introduced method was achieved by the hydrostatic step-pressure micropipette manipulation technique. Additionally the result was reinforced in standard microfluidic shear stress channels. Nevertheless, automated micropipette gave higher sensitivity and less side-effect than the shear stress channel. Using our technique, the probed single cells can be easily picked up and further investigated by other techniques; a definite advantage of the computer controlled micropipette. Our experiments revealed the existence of a

  9. Combination effect on HIV infection in vitro of soluble CD4 and HIV-neutralizing antibodies

    DEFF Research Database (Denmark)

    Hansen, J E; Sørensen, A M; Olofsson, S;

    1994-01-01

    In combination with HIV gp120 V3-loop antibody, two carbohydrate specific neutralizing antibodies (83D4 and 2G12) had a synergistic neutralizing effect on HIV infection. However, sCD4 and an antibody which blocks gp 120/CD4 binding (1B1) both displayed antagonism....

  10. An ELISA for detection of antibodies against influenza A nucleoprotein in humans and various animal species.

    NARCIS (Netherlands)

    G.F. de Boer; W. Back; A.D.M.E. Osterhaus (Ab)

    1990-01-01

    textabstractA double antibody sandwich blocking ELISA, using a monoclonal antibody (MAb) against influenza A nucleoprotein (NP) was developed to detect antibodies against influenza. Collections of serum samples were obtained from human and various animal species. All influenza A subtypes induced ant

  11. Interaction of secretory immunoglobulin A antibodies with Naegleria fowleri trophozoites and collagen type I.

    Science.gov (United States)

    Shibayama, Mineko; Serrano-Luna, José de Jesús; Rojas-Hernández, Saúl; Campos-Rodríguez, Rafael; Tsutsumi, Victor

    2003-03-01

    In this work, we analyzed the in vitro interaction of human secretory immunoglobulin A (sIgA) antibodies with Naegleria fowleri trophozoites and the capacity of these antibodies to inhibit amoeba adherence to collagen type I. We also studied N. fowleri antigens that are recognized by sIgA, using immunoblot assays. Immunocytochemical analysis of the interaction showed a redistribution of antigens on the surface of trophozoites by sIgA antibodies. Ultrastructural analysis of antibody-amoeba interaction showed that besides the patching and cap formation, parasites were capable of eliminating the antigen-antibody complex produced on the surface. sIgA antibodies were capable of inhibiting the in vitro adhesion of trophozoites to collagen type I. We suggest that nonsymptomatic infections by N. fowleri may stimulate a local specific immunity that prevents trophozoite adhesion and invasion of nasal mucosa.

  12. Mechanism of human antibody-mediated neutralization of Marburg virus.

    Science.gov (United States)

    Flyak, Andrew I; Ilinykh, Philipp A; Murin, Charles D; Garron, Tania; Shen, Xiaoli; Fusco, Marnie L; Hashiguchi, Takao; Bornholdt, Zachary A; Slaughter, James C; Sapparapu, Gopal; Klages, Curtis; Ksiazek, Thomas G; Ward, Andrew B; Saphire, Erica Ollmann; Bukreyev, Alexander; Crowe, James E

    2015-02-26

    The mechanisms by which neutralizing antibodies inhibit Marburg virus (MARV) are not known. We isolated a panel of neutralizing antibodies from a human MARV survivor that bind to MARV glycoprotein (GP) and compete for binding to a single major antigenic site. Remarkably, several of the antibodies also bind to Ebola virus (EBOV) GP. Single-particle EM structures of antibody-GP complexes reveal that all of the neutralizing antibodies bind to MARV GP at or near the predicted region of the receptor-binding site. The presence of the glycan cap or mucin-like domain blocks binding of neutralizing antibodies to EBOV GP, but not to MARV GP. The data suggest that MARV-neutralizing antibodies inhibit virus by binding to infectious virions at the exposed MARV receptor-binding site, revealing a mechanism of filovirus inhibition. PMID:25723164

  13. Adhesion mechanisms of Vibrio fluvialis to skin mucus of Epinephelus awoara

    Institute of Scientific and Technical Information of China (English)

    鄢庆枇; 赵敏慧; 王晓露; 邹文政; 陈昌生

    2010-01-01

    Vibrio fluvialis incubated in trypticase soy broth(TSB)showed stronger adhesion to the skin mucus of Epinephelus awoara than V.fluvialis grown on trypticase soy agar(TSA),and this bacterial adhesion was assessed in terms of saturation kinetics.Treating bacteria with antibody against O-antigens resulted in significantly reduced bacterial adhesion.In the early growth stage,the adhering bacteria numbers increased with incubation time,peaked at 24 h,and then dropped sharply.Prior heat treatment of the mucus at ...

  14. Adhesive tape exfoliation

    DEFF Research Database (Denmark)

    Bohr, Jakob

    2015-01-01

    cleaving of a single chunk of graphite. For both cases, parallel and serial exfoliation, it is investigated how many generations of cleavages are needed. An approximate model with the probability distribution expressed as a simple closed form is presented and compared with the simulations.......Single-crystal graphite can be cleaved by the use of an adhesive tape. This was also the initial route for obtaining graphene, a one-layer thick graphite slab. In this letter a few simple and fun considerations are presented in an attempt to shed some light on why this procedure is successful...

  15. [Adhesive cutaneous pharmaceutical forms].

    Science.gov (United States)

    Gafiţanu, E; Matei, I; Mungiu, O C; Pavelescu, M; Mîndreci, I; Apostol, I; Ionescu, G

    1989-01-01

    The adhesive cutaneous pharmaceutical forms aimed to local action release the drug substance in view of a dermatological, traumatological, antirheumatic, cosmetic action. Two such preparations were obtained and their stability, consistency and pH were determined. The "in vitro" tests of their bioavailability revealed the dynamics of calcium ions release according to the associations of each preparation. The bioavailability determined by evaluating the pharmacological response demonstrated the antiinflammatory action obtained by the association of calcium ions with the components extracted from poplar muds. The therapeutical efficiency of the studied preparations has proved in the treatment of some sport injuries.

  16. Blocking and associability change.

    Science.gov (United States)

    Jones, Peter M; Haselgrove, Mark

    2013-07-01

    Blocking of learning about a conditioned stimulus (the "blocked" cue) occurs when it is trained alongside an additional stimulus (the "blocking" cue) that has been previously presented with the outcome. A number of theories (e.g., N. J. Mackintosh. 1975a. A Theory of Attention: Variations in the Associability of Stimuli With Reinforcement. Psychological Review, 82, 276-298; J. M. Pearce & G. Hall. 1980. A Model for Pavlovian Learning: Variation in the Effectiveness of Conditioned But Not Unconditioned Stimuli. Psychological Review, 87, 532-552) account for this attenuation in learning by proposing that attention paid to the blocked cue is restricted. In three experiments, we examined the associability of both blocked and blocking cues. In Experiment 1, rats were trained with a blocking protocol before being given a test discrimination composed of two components; one of these components required the use of the previously blocked cue as a discriminative stimulus, and the other component was soluble by using the blocking cue. To our surprise, the component that depended on the blocked cue was more readily solved than the component dependent on the blocking cue. The results of Experiments 2 and 3 suggest that this is due to the quantity of exposure that each stimulus received during initial training. Implications for theories of blocking, and more widely associative learning, are discussed. PMID:23668185

  17. Blocking and associability change.

    Science.gov (United States)

    Jones, Peter M; Haselgrove, Mark

    2013-07-01

    Blocking of learning about a conditioned stimulus (the "blocked" cue) occurs when it is trained alongside an additional stimulus (the "blocking" cue) that has been previously presented with the outcome. A number of theories (e.g., N. J. Mackintosh. 1975a. A Theory of Attention: Variations in the Associability of Stimuli With Reinforcement. Psychological Review, 82, 276-298; J. M. Pearce & G. Hall. 1980. A Model for Pavlovian Learning: Variation in the Effectiveness of Conditioned But Not Unconditioned Stimuli. Psychological Review, 87, 532-552) account for this attenuation in learning by proposing that attention paid to the blocked cue is restricted. In three experiments, we examined the associability of both blocked and blocking cues. In Experiment 1, rats were trained with a blocking protocol before being given a test discrimination composed of two components; one of these components required the use of the previously blocked cue as a discriminative stimulus, and the other component was soluble by using the blocking cue. To our surprise, the component that depended on the blocked cue was more readily solved than the component dependent on the blocking cue. The results of Experiments 2 and 3 suggest that this is due to the quantity of exposure that each stimulus received during initial training. Implications for theories of blocking, and more widely associative learning, are discussed.

  18. Tangential adhesion strength of cement mortars in masonry

    Directory of Open Access Journals (Sweden)

    Derkach V.N.

    2012-05-01

    Full Text Available The initial shear strength (tangential adhesion and the angle of internal friction in the horizontal plane of mortar joints are among important characteristics, determining the masonry strength and stiffness qualities in case of share. These characteristics influence largely over the limit state approach of buildings and facilities during seismic activity and over wind, crane and other load, causing the panel frame distortion in frame buildings with masonry infill.In the paper the experimental studies results of tangential adhesion strength of cement mortars with solid and hollow ceramic bricks, porous stones, calcium silicate bricks and cellular concrete blocks are presented. This research gives experimental dependences of mortar adhesive strength with mentioned types of masonry units on compressive strength of cement mortar. There is also the comparison of the obtained results with Russian and foreign standards in this paper.

  19. Syndecan proteoglycans and cell adhesion

    DEFF Research Database (Denmark)

    Woods, A; Oh, E S; Couchman, J R

    1998-01-01

    It is now becoming clear that a family of transmembrane proteoglycans, the syndecans, have important roles in cell adhesion. They participate through binding of matrix ligand to their glycosaminoglycan chains, clustering, and the induction of signaling cascades to modify the internal microfilament...... organization. Syndecans can modulate the type of adhesive responses induced by other matrix ligand-receptor interactions, such as those involving the integrins, and so contribute to the control of cell morphology, adhesion and migration....

  20. Adhesion properties of gecko setae

    Science.gov (United States)

    Hill, Ginel; Peattie, Anne; Daniels, Roxanne; Full, Robert; Kenny, Thomas

    2005-03-01

    Millions of keratin hairs on gecko feet, called setae, act as a spectacular dry adhesive. Each seta branches into hundreds of smaller fibers that terminate in spatula-shaped ends. Morphological differences between the setae from different gecko species are suspected to affect both single-seta and whole-animal adhesion properties. Single-seta adhesive force measurements made using a MEMS piezoresistive cantilever capable of two-axis measurements are presented.

  1. Puerperal endometritis and intrauterine adhesions.

    Science.gov (United States)

    Polishuk, W Z; Anteby, S O; Weinstein, D

    1975-08-01

    The role of puerperal endometritis in intrauterine adhesion formation was studied by hysterography in 171 women who had cesarean sections. Of 28 patients who developed significant endometritis, only one developed intracervical adhesions. In the control group of 143 cases, there was also only one such case. Endometritis alone apparently does not play a significant role in intrauterine and endocervical adhesion formation. The possible role of placental fibroblasts in preventing endometrial regeneration is discussed. PMID:1158622

  2. Effects of Roundabout 5 on adhesion, invasion and potential motility of human tongue carcinoma Tb cells

    Institute of Scientific and Technical Information of China (English)

    XIAO Rui; ZHAO yuan; WANG Li-jing; LI Wei-ping

    2011-01-01

    Background Roundabout 5 (R5) is a monoclonal antibody which can neutralize the binding of Roundabout 1 (Robo1)to Slit2. Oral squamous cell carcinoma angiogenesis was significantly inhibited when R5 blocked slit-robo signaling pathway. However, the effect of R5 on the invasion of tongue cancer cells has not been investigated clearly. Methods In this study, we treated human brain metastasis of tongue cancer cell lines (Tb cells) with R5 at different concentrations, and the control Tb cells were treated with 10 mg/ml immunoglobin G 2b (lgG2b). The effect of R5 on the proliferation, adhension, invasion and motility of Tb cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, cell attachment assay on fibronectin (FN), wound assay and chemotaxis assay,respectively. And gelatin-incorporated sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used to investigate the activity of matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9). Results R5 had no effect on the proliferation of Tb cells. However, R5 could significantly inhibit the motility, attachment and chemotaxis of Tb cells to FN, and it could also significantly inhibit the activity of MMP2 and MMP9 in Tb cells. Conclusion R5 can inhibit the adhesion, invasion and motility of human tongue carcinoma Tb cells.

  3. Comparative detection of bacterial adhesion to Caco-2 cells with ELISA, radioactivity and plate count methods.

    Science.gov (United States)

    Le Blay, Gwenaëlle; Fliss, Ismaïl; Lacroix, Christophe

    2004-11-01

    Different methods are used to study bacterial adhesion to intestinal epithelial cells, which is an important step in pathogenic infection as well as in probiotic colonization of the intestinal tract. The aim of this study was to compare the ELISA-based method with more conventional plate count and radiolabeling methods for bacterial adhesion detection. An ELISA-based assay was optimized for the detection of Bifidobacterium longum and Escherichia coli O157:H7, which are low and highly adherent bacteria, respectively. In agreement with previous investigations, a percentage of adhesion below 1% was obtained for B. longum with ELISA. However, high nonspecific background and low positive signals were measured due to the use of polyclonal antibodies and the low adhesion capacity with this strain. In contrast, the ELISA-based method developed for E. coli adhesion detected a high adhesion percentage (15%). For this bacterium the three methods tested gave similar results for the highest bacterial concentrations (6.8 Log CFU added bacteria/well). However, differences among methods increased with the addition of decreased bacterial concentration due to different detection thresholds (5.9, 5.6 and 2.9 Log CFU adherent bacteria/well for radioactivity, ELISA and plate count methods, respectively). The ELISA-based method was shown to be a good predictor for bacterial adhesion compared to the radiolabeling method when good quality specific antibodies were used. This technique is convenient and allows handling of numerous samples.

  4. Aggregation of macrophages and fibroblasts is inhibited by a monoclonal antibody to the hyaluronate receptor

    Energy Technology Data Exchange (ETDEWEB)

    Green, S.J.; Underhill, C.B. (Georgetown Univ. Medical Center, Washington, DC (USA)); Tarone, G. (Univ. of Turin (Italy))

    1988-10-01

    To examine the role of the hyaluronate receptor in cell to cell adhesion, the authors have employed the K-3 monoclonal antibody (MAb) which specifically binds to the hyaluronate receptor and blocks its ability to interact with hyaluronate. In the first set of experiments, they investigated the spontaneous aggregation of SV-3T3 cells, which involves two distinct mechanisms, one of which is dependent upon the presence of divalent cation and the other is independent. The divalent cation-independent aggregation was found to be completely inhibited by both intact and Fab fragments of the K-3 MAb. In contrast, the K-3 MAb had no effect on the divalent cation-dependent aggregation of cells. In a second set of experiments, we examined alveolar macrophages. The presence of hyaluronate receptors on alveolar macrophages was demonstrated by the fact that detergent extracts of these cells could bind ({sup 3})hyaluronate, and this binding was blocked by the K-3 MAb. Immunoblot analysis of alveolar macrophages showed that the hyaluronate receptor had a M{sub r} of 99,500, which is considerably larger than the 85,000 M{sub r} for that on BHK cells. When hyaluronate was added to suspensions of alveolar macrophages, the cells were induced to aggregate. This effect was inhibited by the K-3 MAb, suggesting that the hyaluronate-induced aggregation was mediated by the receptor.

  5. The neural cell adhesion molecule

    DEFF Research Database (Denmark)

    Berezin, V; Bock, E; Poulsen, F M

    2000-01-01

    During the past year, the understanding of the structure and function of neural cell adhesion has advanced considerably. The three-dimensional structures of several of the individual modules of the neural cell adhesion molecule (NCAM) have been determined, as well as the structure of the complex...... between two identical fragments of the NCAM. Also during the past year, a link between homophilic cell adhesion and several signal transduction pathways has been proposed, connecting the event of cell surface adhesion to cellular responses such as neurite outgrowth. Finally, the stimulation of neurite...

  6. Amygdalin Influences Bladder Cancer Cell Adhesion and Invasion In Vitro

    OpenAIRE

    Jasmina Makarević; Jochen Rutz; Eva Juengel; Silke Kaulfuss; Igor Tsaur; Karen Nelson; Jesco Pfitzenmaier; Axel Haferkamp; Blaheta, Roman A.

    2014-01-01

    The cyanogenic diglucoside amygdalin, derived from Rosaceae kernels, is employed by many patients as an alternative anti-cancer treatment. However, whether amygdalin indeed acts as an anti-tumor agent is not clear. Metastasis blocking properties of amygdalin on bladder cancer cell lines was, therefore, investigated. Amygdalin (10 mg/ml) was applied to UMUC-3, TCCSUP or RT112 bladder cancer cells for 24 h or for 2 weeks. Tumor cell adhesion to vascular endothelium or to immobilized collagen as...

  7. Generalized Block Failure

    DEFF Research Database (Denmark)

    Jönsson, Jeppe

    2015-01-01

    Block tearing is considered in several codes as a pure block tension or a pure block shear failure mechanism. However in many situations the load acts eccentrically and involves the transfer of a substantial moment in combination with the shear force and perhaps a normal force. A literature study...... yield lines around the block leads to simple interaction formulas similar to other interaction formulas in the codes.......Block tearing is considered in several codes as a pure block tension or a pure block shear failure mechanism. However in many situations the load acts eccentrically and involves the transfer of a substantial moment in combination with the shear force and perhaps a normal force. A literature study...

  8. Pressure sensitive adhesives from renewable resources

    OpenAIRE

    Maaßen, Wiebke

    2015-01-01

    Pressure-sensitive adhesives (PSAs) represent an important segment of the adhesives market. In this work, novel insights into the adhesive performance of bio-based pressure sensitive adhesives are presented. Three different homopolymers based on fatty acids derived from native vegetable oils as renewable feedstock were characterized in terms of their mechanical and adhesive properties.

  9. Improved Adhesion and Compliancy of Hierarchical Fibrillar Adhesives.

    Science.gov (United States)

    Li, Yasong; Gates, Byron D; Menon, Carlo

    2015-08-01

    The gecko relies on van der Waals forces to cling onto surfaces with a variety of topography and composition. The hierarchical fibrillar structures on their climbing feet, ranging from mesoscale to nanoscale, are hypothesized to be key elements for the animal to conquer both smooth and rough surfaces. An epoxy-based artificial hierarchical fibrillar adhesive was prepared to study the influence of the hierarchical structures on the properties of a dry adhesive. The presented experiments highlight the advantages of a hierarchical structure despite a reduction of overall density and aspect ratio of nanofibrils. In contrast to an adhesive containing only nanometer-size fibrils, the hierarchical fibrillar adhesives exhibited a higher adhesion force and better compliancy when tested on an identical substrate.

  10. Improved Adhesion and Compliancy of Hierarchical Fibrillar Adhesives.

    Science.gov (United States)

    Li, Yasong; Gates, Byron D; Menon, Carlo

    2015-08-01

    The gecko relies on van der Waals forces to cling onto surfaces with a variety of topography and composition. The hierarchical fibrillar structures on their climbing feet, ranging from mesoscale to nanoscale, are hypothesized to be key elements for the animal to conquer both smooth and rough surfaces. An epoxy-based artificial hierarchical fibrillar adhesive was prepared to study the influence of the hierarchical structures on the properties of a dry adhesive. The presented experiments highlight the advantages of a hierarchical structure despite a reduction of overall density and aspect ratio of nanofibrils. In contrast to an adhesive containing only nanometer-size fibrils, the hierarchical fibrillar adhesives exhibited a higher adhesion force and better compliancy when tested on an identical substrate. PMID:26167951

  11. Stretchable, adhesion-tunable dry adhesive by surface wrinkling.

    Science.gov (United States)

    Jeong, Hoon Eui; Kwak, Moon Kyu; Suh, Kahp Y

    2010-02-16

    We introduce a simple yet robust method of fabricating a stretchable, adhesion-tunable dry adhesive by combining replica molding and surface wrinkling. By utilizing a thin, wrinkled polydimethyl siloxane (PDMS) sheet with a thickness of 1 mm with built-in micropillars, active, dynamic control of normal and shear adhesion was achieved. Relatively strong normal (approximately 10.8 N/cm(2)) and shear adhesion (approximately 14.7 N/cm(2)) forces could be obtained for a fully extended (strained) PDMS sheet (prestrain of approximately 3%), whereas the forces could be rapidly reduced to nearly zero once the prestrain was released (prestrain of approximately 0.5%). Moreover, durability tests demonstrated that the adhesion strength in both the normal and shear directions was maintained over more than 100 cycles of attachment and detachment.

  12. Effect of adhesive thickness on adhesively bonded T-joint

    Science.gov (United States)

    Abdullah, A. R.; Afendi, Mohd; Majid, M. S. Abdul

    2013-12-01

    The aim of this work is to analyze the effect of adhesive thickness on tensile strength of adhesively bonded stainless steel T-joint. Specimens were made from SUS 304 Stainless Steel plate and SUS 304 Stainless Steel perforated plate. Four T-joint specimens with different adhesive thicknesses (0.5, 1.0, 1.5 and 2.0 mm) were made. Experiment result shows T-joint specimen with adhesive thickness of 1.0 mm yield highest maximum load. Identical T-joint specimen jointed by spot welding was also tested. Tensile test shows welded T-Joint had eight times higher tensile load than adhesively bonded T-joint. However, in low pressure application such as urea granulator chamber, high tensile strength is not mandatory. This work is useful for designer in fertilizer industry and others who are searching for alternative to spot welding.

  13. Stretchable, Adhesion-Tunable Dry Adhesive by Surface Wrinkling

    KAUST Repository

    Jeong, Hoon Eui

    2010-02-16

    We introduce a simple yet robust method of fabricating a stretchable, adhesion-tunable dry adhesive by combining replica molding and surface wrinkling. By utilizing a thin, wrinkled polydimethyl siloxane (PDMS) sheet with a thickness of 1 mm with built-in micropillars, active, dynamic control of normal and shear adhesion was achieved. Relatively strong normal (∼10.8 N/cm2) and shear adhesion (∼14.7 N/cm2) forces could be obtained for a fully extended (strained) PDMS sheet (prestrain of∼3%), whereas the forces could be rapidly reduced to nearly zero once the prestrain was released (prestrain of ∼0.5%). Moreover, durability tests demonstrated that the adhesion strength in both the normal and shear directions was maintained over more than 100 cycles of attachment and detachment. © 2010 American Chemical Society.

  14. Blocked Randomization with Randomly Selected Block Sizes

    Directory of Open Access Journals (Sweden)

    Jimmy Efird

    2010-12-01

    Full Text Available When planning a randomized clinical trial, careful consideration must be given to how participants are selected for various arms of a study. Selection and accidental bias may occur when participants are not assigned to study groups with equal probability. A simple random allocation scheme is a process by which each participant has equal likelihood of being assigned to treatment versus referent groups. However, by chance an unequal number of individuals may be assigned to each arm of the study and thus decrease the power to detect statistically significant differences between groups. Block randomization is a commonly used technique in clinical trial design to reduce bias and achieve balance in the allocation of participants to treatment arms, especially when the sample size is small. This method increases the probability that each arm will contain an equal number of individuals by sequencing participant assignments by block. Yet still, the allocation process may be predictable, for example, when the investigator is not blind and the block size is fixed. This paper provides an overview of blocked randomization and illustrates how to avoid selection bias by using random block sizes.

  15. Blocked randomization with randomly selected block sizes.

    Science.gov (United States)

    Efird, Jimmy

    2011-01-01

    When planning a randomized clinical trial, careful consideration must be given to how participants are selected for various arms of a study. Selection and accidental bias may occur when participants are not assigned to study groups with equal probability. A simple random allocation scheme is a process by which each participant has equal likelihood of being assigned to treatment versus referent groups. However, by chance an unequal number of individuals may be assigned to each arm of the study and thus decrease the power to detect statistically significant differences between groups. Block randomization is a commonly used technique in clinical trial design to reduce bias and achieve balance in the allocation of participants to treatment arms, especially when the sample size is small. This method increases the probability that each arm will contain an equal number of individuals by sequencing participant assignments by block. Yet still, the allocation process may be predictable, for example, when the investigator is not blind and the block size is fixed. This paper provides an overview of blocked randomization and illustrates how to avoid selection bias by using random block sizes. PMID:21318011

  16. Novel Phosphotidylinositol 4,5-Bisphosphate Binding Sites on Focal Adhesion Kinase

    OpenAIRE

    Jun Feng; Blake Mertz

    2015-01-01

    Focal adhesion kinase (FAK) is a protein tyrosine kinase that is ubiquitously expressed, recruited to focal adhesions, and engages in a variety of cellular signaling pathways. Diverse cellular responses, such as cell migration, proliferation, and survival, are regulated by FAK. Prior to activation, FAK adopts an autoinhibited conformation in which the FERM domain binds the kinase domain, blocking access to the activation loop and substrate binding site. Activation of FAK occurs through confor...

  17. BLOCK H-MATRICES AND SPECTRUM OF BLOCK MATRICES

    Institute of Scientific and Technical Information of China (English)

    黄廷祝; 黎稳

    2002-01-01

    The block H-matrices are studied by the concept of G-functions, several concepts of block matrices are introduced. Equivalent characters of block H-matrices are obtained. Spectrum localizations claracterized by Gfunctions for block matrices are got.

  18. Cleaning properties of dry adhesives

    Institute of Scientific and Technical Information of China (English)

    J.; P.; DíAZ; TéLLEZ; D.; SAMEOTO; C.; MENON

    2010-01-01

    In this paper we present a study into the cleaning properties of synthetic dry adhesives. We have manufactured the adhesive micro-fibres through a low-cost, high yield fabrication method using Sylgard 184 Polydimethylsiloxane (PDMS) as the structural material. We deliberately contaminated the adhesive samples with different sized particles in the micro and macro scales and tested different cleaning methods for their efficacy with respect to each particle size. We investigated different cleaning methods, which included the use of wax moulding, vibration and pressure sensitive adhesives. For adhesion testing we used a custom system with a linear stage and a force sensor indenting a hemispherical probe into the adhesive surface and measuring the pull-off force. To characterize the cleaning efficacy we visually inspected each sample in a microscope and weighed the samples with a microgram-accuracy analytical balance. Results showed that the moulding method induced adhesion recovery in a greater percentage than the other cleaning methods and even helped with the recovery of collapsed posts in some cases. On the other hand pressure sensitive adhesives seem to have the upper hand with regards to certain particle sizes that can potentially pose problems with the moulding method.

  19. Properties of the wall structures made of autoclaved cellular concrete products on the polyurethane foam adhesive

    Directory of Open Access Journals (Sweden)

    A.S. Gorshkov

    2013-08-01

    Full Text Available The article presents information on a test experiment for the construction of masonry fragments made of autoclaved cellular concrete products (ААС blocks on the polyurethane adhesive and the ensuing structural, thermal and technological tests of this type of masonry in specialized laboratories and testing facilities. It is shown that the use of polyurethane foam adhesive to bond the concrete blocks in the masonry walls is technically and economically feasible. On the basis of the tests it was concluded that the laying of concrete blocks on the polyurethane adhesive may be used in the construction of non-load bearing interior and exterior walls of buildings, including the filling of the external frame openings of monolithic buildings with floor bearing of the masonry on load bearing monolithic floors (with appropriate justification of the settlement.

  20. [Retention of adhesive bridges].

    Science.gov (United States)

    Raes, F; De Boever, J

    1994-04-01

    Since the development of adhesive bridges in the early seventies, the retention and therefore the durability of these bridges has been tremendously improved. Conditioning of the non-precious metal by silanisation, careful acid etching of the enamel and the use of the appropriate composite resin are of prime importance. Furthermore, the meticulous preparation with enough interproximal embrace, occlusal rests, interocclusal clearance and cingulum stops is equally important. Including more teeth in the design does not necessarily lead to an improved retention. Besides the material and technical aspects, the whole clinical procedure needs much attention. The retention does not depend on one single factor, but on the precision of all the necessary clinical steps and on a well-defined selection of the material. In this way a five-year survival rate of close to 80% can be obtained. PMID:11830965

  1. Hyaluronan-mediated cellular adhesion

    Science.gov (United States)

    Curtis, Jennifer

    2005-03-01

    Many cells surround themselves with a cushioning halo of polysaccharides that is further strengthened and organized by proteins. In fibroblasts and chrondrocytes, the primary component of this pericellular matrix is hyaluronan, a large linear polyanion. Hyaluronan production is linked to a variety of disease, developmental, and physiological processes. Cells manipulate the concentration of hyaluronan and hyaluronan receptors for numerous activities including modulation of cell adhesion, cell motility, and differentiation. Recent investigations by identify hyaluronan's role in mediating early-stage cell adhesion. An open question is how the cell removes the 0.5-10 micron thick pericellular matrix to allow for further mature adhesion events requiring nanometer scale separations. In this investigation, holographic optical tweezers are used to study the adhesion and viscoelastic properties of chondrocytes' pericellular matrix. Ultimately, we aim to shed further light on the spatial and temporal details of the dramatic transition from micron to nanometer gaps between the cell and its adhesive substrate.

  2. Lesson Thirteen Trifascicular Block

    Institute of Scientific and Technical Information of China (English)

    鲁端; 王劲

    2005-01-01

    @@ A complete trifascicular block would result in complete AV block. The idio ventricular rhythm has a slower rate and a wide QRS complex because the pacemaker is located at the peripheral part of the conduction system distal to the sites of the block1. Such a rhythm may be difficult to differentiate from bifascicular or bundle branch block combined with complete block at a higher level such as the AV node or His bundle2. Besides a slower ventricular rate, a change in the morphology of the QRS complex from a previous known bifascicular pattern would be strongly suggestive of a trifascicular origin of the complete AV block3. A His bundle recording is required for a definitive diagnosis, however.

  3. Block Advertisement Protocol

    OpenAIRE

    Nemirovsky, Danil

    2015-01-01

    Bitcoin, a decentralized cryptocurrency, has attracted a lot of attention from academia, financial service industry and enthusiasts. The trade-off between transaction confirmation throughput and centralization of hash power do not allow Bitcoin to perform at the same level as modern payment systems. Block Advertisement Protocol is proposed as a step to resolve this issue. The protocol allows block mining and block relaying to happen in parallel. The protocol dictates a miner to advertise the ...

  4. Block Cipher Analysis

    DEFF Research Database (Denmark)

    Miolane, Charlotte Vikkelsø

    ensurethat no attack violatesthe securitybounds specifiedbygeneric attack namely exhaustivekey search and table lookup attacks. This thesis contains a general introduction to cryptography with focus on block ciphers and important block cipher designs, in particular the Advanced Encryption Standard...... on small scale variants of AES. In the final part of the thesis we present a new block cipher proposal Present and examine its security against algebraic and differential cryptanalysis in particular....

  5. Interfacial Friction and Adhesion of Polymer Brushes

    KAUST Repository

    Landherr, Lucas J. T.

    2011-08-02

    A bead-probe lateral force microscopy (LFM) technique is used to characterize the interfacial friction and adhesion properties of polymer brushes. Our measurements attempt to relate the physical structure and chemical characteristics of the brush to their properties as thin-film, tethered lubricants. Brushes are synthesized at several chain lengths and surface coverages from polymer chains of polydimethylsiloxane (PDMS), polystyrene (PS), and a poly(propylene glycol)-poly(ethylene glycol) block copolymer (PPG/PEG). At high surface coverage, PDMS brushes manifest friction coefficients (COFs) that are among the lowest recorded for a dry lubricant film (μ ≈ 0.0024) and close to 1 order of magnitude lower than the COF of a bare silicon surface. Brushes synthesized from higher molar mass chains exhibit higher friction forces than those created using lower molar mass polymers. Increased grafting density of chains in the brush significantly reduces the COF by creating a uniform surface of stretched chains with a decreased surface viscosity. Brushes with lower surface tension and interfacial shear stresses manifest the lowest COF. In particular, PDMS chains exhibit COFs lower than PS by a factor of 3.7 and lower than PPG/PEG by a factor of 4.7. A scaling analysis conducted on the surface coverage (δ) in relation to the fraction (ε) of the friction force developing from adhesion predicts a universal relation ε ∼ δ4/3, which is supported by our experimental data. © 2011 American Chemical Society.

  6. Synthesis and interactions with blood of polyetherurethaneurea/polypeptide block copolymers.

    Science.gov (United States)

    Ito, Y; Miyashita, K; Kashiwagi, T; Imanishi, Y

    1993-01-01

    Polyurethane/polypeptide block copolymers were synthesized. Infrared spectroscopy and differential scanning calorimetry revealed that in the block copolymers both segments undergo phase-mixing, while in polyurethane/polypeptide blend both components undergo phase-separation. Contact angle measurement showed that in the block copolymers polyurethane segments tended to appear on the membrane surface, whereas in polyurethane/polypeptide blend polypeptide components appeared on the membrane surface. In vitro nonthrombogenicity of the block copolymers was similar to that of homopolymers or polymer blends, though adhesion and deformation of platelets were suppressed on the block copolymer membranes. PMID:8260582

  7. Adhesion and multi-materials

    International Nuclear Information System (INIS)

    Adhesion is a multidisciplinary science relevant to many practical fields. The main application of adhesion is bonding by adhesives. This technique is widely used in the industrial world and more specifically in the advanced technical domains. Adhesion is also involved in multi-component materials such as coatings, multilayer materials, polymer blends, composite materials... The multidisciplinary aspect of adhesion is well demonstrated by considering the wide variety of concepts, models and theories proposed for its description. An example of the adhesion between a fiber and a matrix in a composite material will lead to a general model relating the molecular properties of the interface to its capacity of stress transfer and hence to the macroscopic mechanical properties of the composite. This relationship is valid whatever the fiber (glass, carbon, polymeric) or the polymer matrix (thermoplastics, thermosetting). Any deviation from this model can be attributed to the existence of an interfacial zone or interphase exhibiting properties, mainly mechanical properties, different from the bulk matrix. Two examples are examined: the first one deals with the creation of a trans crystalline interphase in a semi-crystalline thermoplastic matrix and the second one is concerned with the formation of a pseudo glassy interphase in an elastomer matrix. These examples stress the need for complementary approaches in the understanding of adhesion phenomena at different levels of knowledge, from molecular to macroscopic. They also show how important it is to understand the mechanisms of formation of inter phases in order to be able to master the performance of multicomponent materials. (Author)

  8. Mast cells facilitate local VEGF release as an early event in the pathogenesis of postoperative peritoneal adhesions.

    LENUS (Irish Health Repository)

    Cahill, Ronan A

    2012-02-03

    BACKGROUND: Peritoneal injury sustained at laparotomy may evoke local inflammatory responses that result in adhesion formation. Peritoneal mast cells are likely to initiate this process, whereas vascular permeability\\/endothelial growth factor (VEGF) may facilitate the degree to which subsequent adhesion formation occurs. METHODS: Mast cell deficient mice (WBB6F1-\\/-), along with their mast cell sufficient counterparts (WBB6F1+\\/+), underwent a standardized adhesion-inducing operation (AIS) with subsequent sacrifice and adhesion assessment 14 days later in a blinded fashion. Additional CD-1 and WBB6F1+\\/+, and WBB6F1-\\/- mice were killed 2, 6, 12, and 24 hours after operation for measurement of VEGF by ELISA in systemic serum and peritoneal lavage fluid. Two further groups of CD-1 mice underwent AIS and received either a single perioperative dose of anti-VEGF monoclonal antibody (10 mug\\/mouse) or a similar volume of IgG isotypic antibody and adhesion formation 2 weeks later was evaluated. RESULTS: WBB6F1-\\/- mice had less adhesions then did their WBB6F1+\\/+ counterparts (median [interquartile range] adhesion score 3[3-3] vs 1.5[1-2] respectively; P < .003). Local VEGF release peaked 6 hours after AIS in both WBB6F1+\\/+ and CD-1 mice whereas levels remained at baseline in WBB6F1-\\/- mice. CD-1 mice treated with a single dose of anti-VEGF therapy during operation had less adhesions than controls (2[1.25-2] vs 3[2.25-3], P = .0002). CONCLUSIONS: Mast cells and VEGF are central to the formation of postoperative intra-abdominal adhesions with mast cells being responsible, either directly or indirectly, for VEGF release into the peritoneal cavity after operation. In tandem with the recent clinical success of anti-VEGF monoclonal antibodies in oncologic practice, our observations suggest an intriguing avenue for research and development of anti-adhesion strategy.

  9. Interleukin-8 induces motile behavior and loss of focal adhesions in primary fibroblasts

    DEFF Research Database (Denmark)

    Dunlevy, J R; Couchman, J R

    1995-01-01

    causes an increase in the percentage of cells lacking focal adhesions. Most of the IL-8-stimulated cells not only exhibit a lack of focal adhesions but also have a migratory phenotype that includes a protrusive leading edge and trailing tail. In addition, IL-8 was found to promote primary fibroblast...... locomotion and have fully characterized this system using newborn rat heart conditioned medium. The main stimulus in heart conditioned medium that is responsible for the lack of focal adhesions in the majority of cells can be immunoprecipitated using a polyclonal antibody against recombinant human IL-8....... Additionally, video microscopy assays using heart conditioned medium depleted with the IL-8 antibody show an increase in the percentage of stationary cells, a consequent decrease in the percentage of migrating cells, and a twofold increase in the mitotic rate. Interleukin-1 alpha and tumor necrosis factor...

  10. Development and characterization of a novel hydrogel adhesive for soft tissue applications

    Science.gov (United States)

    Sanders, Lindsey Kennedy

    With laparoscopic and robotic surgical techniques advancing, the need for an injectable surgical adhesive is growing. To be effective, surgical adhesives for internal organs require bulk strength and compliance to avoid rips and tears, and adhesive strength to avoid leakage at the application site, while not hindering the natural healing process. Although a number of tissue adhesives and sealants approved by the FDA for surgical use are currently available, attaining a useful balance in all of these qualities has proven difficult, particularly when considering applications involving highly expandable tissue, such as bladder and lung. The long-term goal of this project is to develop a hydrogel-based tissue adhesive that provides proper mechanical properties to eliminate the need for sutures in various soft tissue applications. Tetronic (BASF), a 4-arm poly(propylene oxide)-poly(ethylene oxide) (PPO-PEO) block copolymer, has been selected as the base material for the adhesive hydrogel system. Solutions of Tetronic T1107 can support reverse thermal gelation at physiological temperatures, which can be combined with covalent crosslinking to achieve a "tandem gelation" process making it ideal for use as a tissue adhesive. The objective of this doctoral thesis research is to improve the performance of the hydrogel based tissue adhesive developed previously by Cho and co-workers by applying a multi-functionalization of Tetronic. Specifically, this research aimed to improve bonding strength of Tetronic tissue adhesive using bi-functional modification, incorporate hemostatic function to the bi-functional Tetronic hydrogel, and evaluate the safety of bi-functional Tetronic tissue adhesive both in vitro and in vivo. In summary, we have developed a fast-curing, mechanically strong hemostatic tissue adhesive that can control blood loss in wet conditions during wound treatment applications (bladder, liver and muscle). Specifically, the bi-functional Tetronic adhesive (TAS) with a

  11. Focal Adhesion Kinases in Adhesion Structures and Disease

    Directory of Open Access Journals (Sweden)

    Pierre P. Eleniste

    2012-01-01

    Full Text Available Cell adhesion to the extracellular matrix (ECM is essential for cell migration, proliferation, and embryonic development. Cells can contact the ECM through a wide range of matrix contact structures such as focal adhesions, podosomes, and invadopodia. Although they are different in structural design and basic function, they share common remodeling proteins such as integrins, talin, paxillin, and the tyrosine kinases FAK, Pyk2, and Src. In this paper, we compare and contrast the basic organization and role of focal adhesions, podosomes, and invadopodia in different cells. In addition, we discuss the role of the tyrosine kinases, FAK, Pyk2, and Src, which are critical for the function of the different adhesion structures. Finally, we discuss the essential role of these tyrosine kinases from the perspective of human diseases.

  12. Focal adhesion kinases in adhesion structures and disease.

    Science.gov (United States)

    Eleniste, Pierre P; Bruzzaniti, Angela

    2012-01-01

    Cell adhesion to the extracellular matrix (ECM) is essential for cell migration, proliferation, and embryonic development. Cells can contact the ECM through a wide range of matrix contact structures such as focal adhesions, podosomes, and invadopodia. Although they are different in structural design and basic function, they share common remodeling proteins such as integrins, talin, paxillin, and the tyrosine kinases FAK, Pyk2, and Src. In this paper, we compare and contrast the basic organization and role of focal adhesions, podosomes, and invadopodia in different cells. In addition, we discuss the role of the tyrosine kinases, FAK, Pyk2, and Src, which are critical for the function of the different adhesion structures. Finally, we discuss the essential role of these tyrosine kinases from the perspective of human diseases. PMID:22888421

  13. Photovoltaic module with adhesion promoter

    Science.gov (United States)

    Xavier, Grace

    2013-10-08

    Photovoltaic modules with adhesion promoters and methods for fabricating photovoltaic modules with adhesion promoters are described. A photovoltaic module includes a solar cell including a first surface and a second surface, the second surface including a plurality of interspaced back-side contacts. A first glass layer is coupled to the first surface by a first encapsulating layer. A second glass layer is coupled to the second surface by a second encapsulating layer. At least a portion of the second encapsulating layer is bonded directly to the plurality of interspaced back-side contacts by an adhesion promoter.

  14. Adhesives from modified soy protein

    Science.gov (United States)

    Sun, Susan; Wang, Donghai; Zhong, Zhikai; Yang, Guang

    2008-08-26

    The, present invention provides useful adhesive compositions having similar adhesive properties to conventional UF and PPF resins. The compositions generally include a protein portion and modifying ingredient portion selected from the group consisting of carboxyl-containing compounds, aldehyde-containing compounds, epoxy group-containing compounds, and mixtures thereof. The composition is preferably prepared at a pH level at or near the isoelectric point of the protein. In other preferred forms, the adhesive composition includes a protein portion and a carboxyl-containing group portion.

  15. Block Scheduling Revisited.

    Science.gov (United States)

    Queen, J. Allen

    2000-01-01

    Successful block scheduling depends on provision of initial and ongoing instructional training. Teaching strategies should vary and include cooperative learning, the case method, the socratic seminar, synectics, concept attainment, the inquiry method, and simulations. Recommendations for maximizing block scheduling are outlined. (Contains 52…

  16. Surviving Block Scheduling.

    Science.gov (United States)

    Haley, Marjorie

    A discussion of block scheduling for second language instruction looks at the advantages and disadvantages and offers some suggestions for classroom management and course organization. It is argued that block scheduling may offer a potential solution to large classes, insufficient time for labs, too little individualized instruction; few…

  17. Focal Adhesion Kinases in Adhesion Structures and Disease

    OpenAIRE

    Pierre P. Eleniste; Angela Bruzzaniti

    2012-01-01

    Cell adhesion to the extracellular matrix (ECM) is essential for cell migration, proliferation, and embryonic development. Cells can contact the ECM through a wide range of matrix contact structures such as focal adhesions, podosomes, and invadopodia. Although they are different in structural design and basic function, they share common remodeling proteins such as integrins, talin, paxillin, and the tyrosine kinases FAK, Pyk2, and Src. In this paper, we compare and contrast the basic organiza...

  18. Monoclonal antibodies and cancer

    International Nuclear Information System (INIS)

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

  19. Bidirectional remodeling of β1-integrin adhesions during chemotropic regulation of nerve growth

    Directory of Open Access Journals (Sweden)

    Carlstrom Lucas P

    2011-11-01

    Full Text Available Abstract Background Chemotropic factors in the extracellular microenvironment guide nerve growth by acting on the growth cone located at the tip of extending axons. Growth cone extension requires the coordination of cytoskeleton-dependent membrane protrusion and dynamic adhesion to the extracellular matrix, yet how chemotropic factors regulate these events remains an outstanding question. We demonstrated previously that the inhibitory factor myelin-associated glycoprotein (MAG triggers endocytic removal of the adhesion receptor β1-integrin from the growth cone surface membrane to negatively remodel substrate adhesions during chemorepulsion. Here, we tested how a neurotrophin might affect integrin adhesions. Results We report that brain-derived neurotropic factor (BDNF positively regulates the formation of substrate adhesions in axonal growth cones during stimulated outgrowth and prevents removal of β1-integrin adhesions by MAG. Treatment of Xenopus spinal neurons with BDNF rapidly triggered β1-integrin clustering and induced the dynamic formation of nascent vinculin-containing adhesion complexes in the growth cone periphery. Both the formation of nascent β1-integrin adhesions and the stimulation of axon extension by BDNF required cytoplasmic calcium ion signaling and integrin activation at the cell surface. Exposure to MAG decreased the number of β1-integrin adhesions in the growth cone during inhibition of axon extension. In contrast, the BDNF-induced adhesions were resistant to negative remodeling by MAG, correlating with the ability of BDNF pretreatment to counteract MAG-inhibition of axon extension. Pre-exposure to MAG prevented the BDNF-induced formation of β1-integrin adhesions and blocked the stimulation of axon extension by BDNF. Conclusions Altogether, these findings demonstrate the neurotrophin-dependent formation of integrin-based adhesions in the growth cone and reveal how a positive regulator of substrate adhesions can block

  20. Denture Adhesives - A Literature Review

    Directory of Open Access Journals (Sweden)

    Sudhanshu Shekhar

    2016-06-01

    Full Text Available Successful complete denture treatment combines exemplary technique, effective patient rapport and education and familiarity with all possible management options to provide the highest degree of patient satisfaction. Dentists need to know about denture adhesives to be able to identify those patients who actually need them and to be able to educate them about the advantages, disadvantages and correct use of these products. Denture adhesives are commercially available nontoxic, soluble materials that when applied to the tissue surface of dentures enhance their retention, stability and performance. They were introduced in dentistry in the late 18th century. The first patent related to adhesives was issued in 1913, followed in the 1920’s and 1930’s. The purpose of the use of denture adhesives can be described as to subjectively benefit denture-wearers with improved stability, retention and comfort of their dentures, and with improved incisal force, masticatory ability, and confidence.

  1. Underwater adhesion: The barnacle way

    Digital Repository Service at National Institute of Oceanography (India)

    Khandeparker, L.; Anil, A.C.

    rosa and demonstrated the stimulatory effect of dopamine and noradrenaline on such secretion. Their study indicated exocytosis to be the major mode of cement secretion and suggest that gradual, localized exocytotic secretion of cement triggered... by catecholaminergic neurons to be the key mechanism during permanent attachment by barnacle cyprids [51]. Properties of barnacle adhesive The resistance to chemical breakdown by barnacle adhesive caused a major problem in its characterization. However...

  2. Laser surface modification and adhesion

    CERN Document Server

    Mittal, K L

    2014-01-01

    The book provides a unique overview on laser techniques and applications for the purpose of improving adhesion by altering surface chemistry and topography/morphology of the substrate. It details laser surface modification techniques for a wide range of industrially relevant materials (plastics, metals, ceramics, composites) with the aim to improve and enhance their adhesion to other materials. The joining of different materials is of critical importance in the fabrication of many and varied products.

  3. Notch-Mediated Cell Adhesion

    OpenAIRE

    Akihiko Murata; Shin-Ichi Hayashi

    2016-01-01

    Notch family members are generally recognized as signaling molecules that control various cellular responses in metazoan organisms. Early fly studies and our mammalian studies demonstrated that Notch family members are also cell adhesion molecules; however, information on the physiological roles of this function and its origin is limited. In this review, we discuss the potential present and ancestral roles of Notch-mediated cell adhesion in order to explore its origin and the initial roles of...

  4. Mechanisms of adhesion in geckos.

    Science.gov (United States)

    Autumn, Kellar; Peattie, Anne M

    2002-12-01

    The extraordinary adhesive capabilities of geckos have challenged explanation for millennia, since Aristotle first recorded his observations. We have discovered many of the secrets of gecko adhesion, yet the millions of dry, adhesive setae on the toes of geckos continue to generate puzzling new questions and valuable answers. Each epidermally-derived, keratinous seta ends in hundreds of 200 nm spatular tips, permitting intimate contact with rough and smooth surfaces alike. Prior studies suggested that adhesive force in gecko setae was directly proportional to the water droplet contact angle (θ) , an indicator of the free surface energy of a substrate. In contrast, new theory suggests that adhesion energy between a gecko seta and a surface (W(GS)) is in fact proportional to (1 + cosθ), and only for θ > 60°. A reanalysis of prior data, in combination with our recent study, support the van der Waals hypothesis of gecko adhesion, and contradict surface hydrophobicity as a predictor of adhesion force. Previously, we and our collaborators measured the force production of a single seta. Initial efforts to attach a seta failed because of improper 3D orientation. However, by simulating the dynamics of gecko limbs during climbing (based on force plate data) we discovered that, in single setae, a small normal preload, combined with a 5 μm displacement yielded a very large adhesive force of 200 microNewton (μN), 10 times that predicted by whole-animal measurements. 6.5 million setae of a single tokay gecko attached maximally could generate 130 kg force. This raises the question of how geckos manage to detach their feet in just 15 ms. We discovered that simply increasing the angle that the setal shaft makes with the substrate to 30° causes detachment. Understanding how simultaneous attachment and release of millions of setae are controlled will require an approach that integrates levels ranging from molecules to lizards.

  5. Adhesive capsulitis: a case report

    OpenAIRE

    Kazemi, Mohsen

    2000-01-01

    Adhesive capsulitis or frozen shoulder is an uncommon entity in athletes. However, it is a common cause of shoulder pain and disability in the general population. Although it is a self limiting ailment, its rather long, restrictive and painful course forces the affected person to seek treatment. Conservative management remains the mainstay treatment of adhesive capsulitis. This includes chiropractic manipulation of the shoulder, therapeutic modalities, mobilization, exercise, soft tissue ther...

  6. Unfolding Grammars in Adhesive Categories

    OpenAIRE

    Baldan, Paolo; Corradini, Andrea; Heindel, Tobias; König, Barbara; Sobocinski, Pawel

    2009-01-01

    We generalize the unfolding semantics, previously developed for concrete formalisms such as Petri nets and graph grammars, to the abstract setting of (single pushout) rewriting over adhesive categories. The unfolding construction is characterized as a coreflection, i.e. the unfolding functor arises as the right adjoint to the embedding of the category of occurrence grammars into the category of grammars.As the unfolding represents potentially infinite computations, we need to work in adhesive...

  7. [VGKC-complex antibodies].

    Science.gov (United States)

    Watanabe, Osamu

    2013-04-01

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

  8. Predictability of blocking

    International Nuclear Information System (INIS)

    Tibaldi and Molteni (1990, hereafter referred to as TM) had previously investigated operational blocking predictability by the ECMWF model and the possible relationships between model systematic error and blocking in the winter season of the Northern Hemisphere, using seven years of ECMWF operational archives of analyses and day 1 to 10 forecasts. They showed that fewer blocking episodes than in the real atmosphere were generally simulated by the model, and that this deficiency increased with increasing forecast time. As a consequence of this, a major contribution to the systematic error in the winter season was shown to derive from the inability of the model to properly forecast blocking. In this study, the analysis performed in TM for the first seven winter seasons of the ECMWF operational model is extended to the subsequent five winters, during which model development, reflecting both resolution increases and parametrisation modifications, continued unabated. In addition the objective blocking index developed by TM has been applied to the observed data to study the natural low frequency variability of blocking. The ability to simulate blocking of some climate models has also been tested

  9. Fibrillar Adhesive for Climbing Robots

    Science.gov (United States)

    Pamess, Aaron; White, Victor E.

    2013-01-01

    A climbing robot needs to use its adhesive patches over and over again as it scales a slope. Replacing the adhesive at each step is generally impractical. If the adhesive or attachment mechanism cannot be used repeatedly, then the robot must carry an extra load of this adhesive to apply a fresh layer with each move. Common failure modes include tearing, contamination by dirt, plastic deformation of fibers, and damage from loading/ unloading. A gecko-like fibrillar adhesive has been developed that has been shown useful for climbing robots, and may later prove useful for grasping, anchoring, and medical applications. The material consists of a hierarchical fibrillar structure that currently contains two levels, but may be extended to three or four levels in continuing work. The contacting level has tens of thousands of microscopic fibers made from a rubberlike material that bend over and create intimate contact with a surface to achieve maximum van der Waals forces. By maximizing the real area of contact that these fibers make and minimizing the bending energy necessary to achieve that contact, the net amount of adhesion has been improved dramatically.

  10. Gold nanoparticles for cancer detection and treatment: The role of adhesion

    International Nuclear Information System (INIS)

    This paper presents the results of an experimental study of the effects of adhesion between gold nanoparticles and surfaces that are relevant to the potential applications in cancer detection and treatment. Adhesion is measured using a dip coating/atomic force microscopy (DC/AFM) technique. The adhesion forces are obtained for dip-coated gold nanoparticles that interact with peptide or antibody-based molecular recognition units (MRUs) that attach specifically to breast cancer cells. They include MRUs that attach specifically to receptors on breast cancer cells. Adhesion forces between anti-cancer drugs such as paclitaxel, and the constituents of MRU-conjugated Au nanoparticle clusters, are measured using force microscopy techniques. The implications of the results are then discussed for the design of robust gold nanoparticle clusters and for potential applications in localized drug delivery and hyperthermia

  11. Gold nanoparticles for cancer detection and treatment: The role of adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Oni, Y. [Princeton Institute for Science and Technology of Materials (PRISM), Princeton University, 70 Prospect Street, Princeton, New Jersey 08544 (United States); Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, New Jersey 08544 (United States); Hao, K. [Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 (United States); Dozie-Nwachukwu, S.; Odusanya, O. S. [African University of Science and Technology (AUST), Kilometer 10, Airport Road, Abuja, Federal Capital Territory (Nigeria); Sheda Science and Technology Complex (SHESTCO), Gwagwalada, Abuja, Federal Capital Territory (Nigeria); Obayemi, J.D. [African University of Science and Technology (AUST), Kilometer 10, Airport Road, Abuja, Federal Capital Territory (Nigeria); Anuku, N. [Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, New Jersey 08544 (United States); Department of Chemistry and Chemical Technology, Bronx Community College, New York, New York 10453 (United States); Soboyejo, W. O. [Princeton Institute for Science and Technology of Materials (PRISM), Princeton University, 70 Prospect Street, Princeton, New Jersey 08544 (United States); Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, New Jersey 08544 (United States); African University of Science and Technology (AUST), Kilometer 10, Airport Road, Abuja, Federal Capital Territory (Nigeria)

    2014-02-28

    This paper presents the results of an experimental study of the effects of adhesion between gold nanoparticles and surfaces that are relevant to the potential applications in cancer detection and treatment. Adhesion is measured using a dip coating/atomic force microscopy (DC/AFM) technique. The adhesion forces are obtained for dip-coated gold nanoparticles that interact with peptide or antibody-based molecular recognition units (MRUs) that attach specifically to breast cancer cells. They include MRUs that attach specifically to receptors on breast cancer cells. Adhesion forces between anti-cancer drugs such as paclitaxel, and the constituents of MRU-conjugated Au nanoparticle clusters, are measured using force microscopy techniques. The implications of the results are then discussed for the design of robust gold nanoparticle clusters and for potential applications in localized drug delivery and hyperthermia.

  12. Solid-supported polymer bilayers formed by coil-coil block copolymers.

    Science.gov (United States)

    Yang, Yan-Ling; Tsao, Heng-Kwong; Sheng, Yu-Jane

    2016-08-14

    The formation and physical properties of solid-supported polymer bilayers (SPBs) on an adhesive substrate have been explored by dissipative particle dynamics simulations. A SPB is developed by the adsorption of vesicles formed by diblock copolymers in a selective solvent. The adsorbed vesicle can remain intact or become ruptured into a SPB, depending on the interaction between solvophobic blocks and solvent and the interaction between solvophilic blocks and the substrate. The morphological phase diagram of adsorbed vesicles is acquired. The influence of polymer adhesion strength and solvophobicity on the geometrical and mechanical properties of a SPB is systematically studied as well. It is found that vesicular disruption is easily triggered for strong adhesion strength. Moreover, for strong adhesion strength and weak solvophobicity, the fluctuation of membrane height is impeded while the area of fluctuation is enhanced. PMID:27418114

  13. Dynamic mechanical and thermal properties of seven polyurethane adhesives

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, D.M.

    1981-03-01

    Seven polyurethane adhesives have been developed at Lawrence Livermore National Laboratory (LLNL). These adhesives, designated Halthanes were synthesized because of OSHA restrictions on the use of the curing agent methylene bis(2-chloroaniline). Four of the Halthanes were made from LLNL-developed 4,4'-methylene bis(phenylisocyanate) terminated prepolymers cured with a blend of polyols; three were made from an LLNL-developed prepolymer terminated with Hylene W and cured with aromatic diamines. In this paper the dynamic mechanical and thermal behavior of these seven segmented polyurethanes are discussed. The chemical structure of the hard and soft segments, the concentrations of each block, and the presence of tetrafunctional crosslinker determined the dynamic mechanical and thermal properties of the three types of polyurethane adhesives, 73-, 87-, and 88-series Halthanes studied. Aromatic-aliphatic MDI- butanediol urethane hard segments produce lower modulus (10/sup 6/ Pa) materials in the rubbery region than cyclic unsaturated-aromatic urea hard segments. Incorporation of chemical crosslinks in the hard segments extended the rubbery plateau beyond the hard segment transitions up to temperatures where the polymer begins to degrade. Concentration of hard and soft segments can also be used to control the modulus between the glass transition temperatures of the two blocks.

  14. Block copolymer battery separator

    Energy Technology Data Exchange (ETDEWEB)

    Wong, David; Balsara, Nitash Pervez

    2016-04-26

    The invention herein described is the use of a block copolymer/homopolymer blend for creating nanoporous materials for transport applications. Specifically, this is demonstrated by using the block copolymer poly(styrene-block-ethylene-block-styrene) (SES) and blending it with homopolymer polystyrene (PS). After blending the polymers, a film is cast, and the film is submerged in tetrahydrofuran, which removes the PS. This creates a nanoporous polymer film, whereby the holes are lined with PS. Control of morphology of the system is achieved by manipulating the amount of PS added and the relative size of the PS added. The porous nature of these films was demonstrated by measuring the ionic conductivity in a traditional battery electrolyte, 1M LiPF.sub.6 in EC/DEC (1:1 v/v) using AC impedance spectroscopy and comparing these results to commercially available battery separators.

  15. Development and maturation of norovirus antibodies in childhood.

    Science.gov (United States)

    Blazevic, Vesna; Malm, Maria; Honkanen, Hanna; Knip, Mikael; Hyöty, Heikki; Vesikari, Timo

    2016-04-01

    The burden of norovirus (NoV) gastroenteritis is substantial in young children. Maternal antibodies are thought to protect a child from NoV infection in early infancy but subsequent development of NoV-specific protective immunity in children is still largely unexplored. We have determined NoV-specific antibody seroconversion to GII.4 virus-like particles as an indicator of NoV infection in two children prospectively followed from birth to eight years of age. Blocking activity and affinity maturation of maternal and serum IgG antibodies were evaluated. Our results show that multiple infections occur in children up to eight years of age. The titer, blocking activity and avidity of maternal antibodies determined susceptibility of an infant to NoV infection. NoV GII.4-specific antibodies with high blocking potential and avidity were developed at two to three years of age and were retained throughout the follow-up. Subsequent NoV infections may have contributed to the duration of protective NoV-specific immune responses that lasted for several years. This study adds to current understanding of the duration of passive protection by maternal antibodies and the duration and quality of acquired immunity following primary and subsequent NoV infections in infants and young children, who are the main target group for NoV vaccine development. PMID:26724451

  16. Blocking in Category Learning

    OpenAIRE

    Bott, Lewis; Hoffman, Aaron B.; Murphy, Gregory L.

    2007-01-01

    Many theories of category learning assume that learning is driven by a need to minimize classification error. When there is no classification error, therefore, learning of individual features should be negligible. We tested this hypothesis by conducting three category learning experiments adapted from an associative learning blocking paradigm. Contrary to an error-driven account of learning, participants learned a wide range of information when they learned about categories, and blocking effe...

  17. Optimizing Adhesive Design by Understanding Compliance.

    Science.gov (United States)

    King, Daniel R; Crosby, Alfred J

    2015-12-23

    Adhesives have long been designed around a trade-off between adhesive strength and releasability. Geckos are of interest because they are the largest organisms which are able to climb utilizing adhesive toepads, yet can controllably release from surfaces and perform this action over and over again. Attempting to replicate the hierarchical, nanoscopic features which cover their toepads has been the primary focus of the adhesives field until recently. A new approach based on a scaling relation which states that reversible adhesive force capacity scales with (A/C)(1/2), where A is the area of contact and C is the compliance of the adhesive, has enabled the creation of high strength, reversible adhesives without requiring high aspect ratio, fibrillar features. Here we introduce an equation to calculate the compliance of adhesives, and utilize this equation to predict the shear adhesive force capacity of the adhesive based on the material components and geometric properties. Using this equation, we have investigated important geometric parameters which control force capacity and have shown that by controlling adhesive shape, adhesive force capacity can be increased by over 50% without varying pad size. Furthermore, we have demonstrated that compliance of the adhesive far from the interface still influences shear adhesive force capacity. Utilizing this equation will allow for the production of adhesives which are optimized for specific applications in commercial and industrial settings.

  18. Innovative Electrostatic Adhesion Technologies

    Science.gov (United States)

    Bryan, Tom; Macleod, Todd; Gagliano, Larry; Williams, Scott; McCoy, Brian

    2015-01-01

    Developing specialized Electro-Static grippers (commercially used in Semiconductor Manufacturing and in package handling) will allow gentle and secure Capture, Soft Docking, and Handling of a wide variety of materials and shapes (such as upper-stages, satellites, arrays, and possibly asteroids) without requiring physical features or cavities for a pincher or probe or using harpoons or nets. Combined with new rigid boom mechanisms or small agile chaser vehicles, flexible, high speed Electro-Static Grippers can enable compliant capture of spinning objects starting from a safe stand-off distance. Electroadhesion (EA) can enable lightweight, ultra-low-power, compliant attachment in space by using an electrostatic force to adhere similar and dissimilar surfaces. A typical EA enabled device is composed of compliant space-rated materials, such as copper-clad polyimide encapsulated by polymers. Attachment is induced by strong electrostatic forces between any substrate material, such as an exterior satellite panel and a compliant EA gripper pad surface. When alternate positive and negative charges are induced in adjacent planar electrodes in an EA surface, the electric fields set up opposite charges on the substrate and cause an electrostatic adhesion between the electrodes and the induced charges on the substrate. Since the electrodes and the polymer are compliant and can conform to uneven or rough surfaces, the electrodes can remain intimately close to the entire surface, enabling high clamping pressures. Clamping pressures of more than 3 N/cm2 in shear can be achieved on a variety of substrates with ultra-low holding power consumption (measured values are less than 20 microW/Newton weight held). A single EA surface geometry can be used to clamp both dielectric and conductive substrates, with slightly different physical mechanisms. Furthermore EA clamping requires no normal force be placed on the substrate, as conventional docking requires. Internally funded research and

  19. Innovative Electrostatic Adhesion Technologies

    Science.gov (United States)

    Gagliano, L.; Bryan, T.; Williams, S.; McCoy, B.; MacLeod, T.

    Developing specialized Electro-Static grippers (commercially used in Semiconductor Manufacturing and in package handling) will allow gentle and secure Capture, Soft Docking, and Handling of a wide variety of materials and shapes (such as upper-stages, satellites, arrays, and possibly asteroids) without requiring physical features or cavities for a pincher or probe or using harpoons or nets. Combined with new rigid boom mechanisms or small agile chaser vehicles, flexible, high speed Electro-Static Grippers can enable compliant capture of spinning objects starting from a safe stand-off distance. Electroadhesion (EA) can enable lightweight, ultra-low-power, compliant attachment in space by using an electrostatic force to adhere similar and dissimilar surfaces. A typical EA enabled device is composed of compliant space-rated materials, such as copper-clad polyimide encapsulated by polymers. Attachment is induced by strong electrostatic forces between any substrate material, such as an exterior satellite panel and a compliant EA surface. When alternate positive and negative charges are induced in adjacent planar electrodes in an EA surface, the electric fields set up opposite charges on the substrate and cause an electrostatic adhesion between the electrodes and the induced charges on the substrate. Since the electrodes and the polymer are compliant and can conform to uneven or rough surfaces, the electrodes can remain intimately close to the entire surface, enabling high clamping pressures. Clamping pressures of more than 3 N/cm2 in shear can be achieved on a variety of substrates with ultra-low holding power consumption (measured values are less than 20 microW/Newton weight held). A single EA surface geometry can be used to clamp both dielectric and conductive substrates, with slightly different physical mechanisms. Furthermore EA clamping requires no normal force be placed on the substrate, as conventional docking requires. Internally funded research and development

  20. Elastocapilllarity in insect adhesion: the case of beetle adhesive hair

    Science.gov (United States)

    Gernay, Sophie; Gilet, Tristan; Lambert, Pierre; Federle, Walter

    2014-11-01

    The feet of many insects are covered with dense arrays of hair-like structures called setae. Liquid capillary bridges at the tip of these micrometric structures are responsible for the controlled adhesion of the insect on a large variety of substrates. The resulting adhesion force can exceed several times the body weight of the insect. The high aspect-ratio of setae suggests that flexibility is a key ingredient in this capillary-based adhesion mechanism. There is indeed a strong coupling between their elastic deformation and the shape of the liquid meniscus. In this experimental work, we observe and quantify the local deflection of dock beetle seta tips under perpendicular loading using interference microscopy. Our results are then interpreted in the light of an analytic model of elastocapillarity. This research has been funded by the FRIA/FNRS and the Interuniversity Attraction Poles Programme (IAP 7/38 MicroMAST) initiated by the Belgian Science Policy Office.

  1. Localization of 131I-labelled monoclonal antibody ERIC1 in a subcutaneous xenograft model of neuroblastoma in SCID mice

    International Nuclear Information System (INIS)

    Our purpose was to evaluate a novel strategy of immunolocalization of human neuroblastoma by targeting the neural cell adhesion molecule (NCAM), which is over-expressed on neuroblastoma. Neuroblastoma is the most frequent solid extracranial childhood tumour and also the most common neoplasm in the first year of life. The most frequent metastatic sites are bone, bone marrow and liver. The neural cell adhesion molecule (NCAM) is constitutively expressed on nearly 100% of all neuroblastomas. NCAM has been successfully used as a target for immunotoxines and bi-specific antibodies in multiple myeloma, small cell lung cancer, glioma or neuroblastoma, in vitro and in vivo. NCAM expression was quantified on established neuroblastoma cells by real time PCR and NCAM expression on the cell surface shown by flow cytometry. A SCID mouse model using IMR5-75 neuroblastoma cells to induce subcutaneous tumour growth was established. 131I was used to label monoclonal NCAM specific ERIC1 antibodies generating the 131I-ERIC1 antibody, which shows a high affinity to NCAM also after labelling (KD= 9 x 10-8). Groups of five to six mice received intravenous injections of 3-9 MBq of 131I-ERIC1 on day 0 into the tail vein. At time points 2.5 h, 24 h, 48 h, 72 h and 96 h post injection mice were sacrificed by cervical dislocation. Blood, liver, spleen, kidneys, muscle, femur, thyroid, intestines, lung, tumour and urine were removed and weighed. Organ-specific radioactivity was measured in a well-counter as well as that of the tail and remnant cadavers. Data were calculated as dose per gram of tissue (%ID/g) and tumour to non-tumour ratios (T/NT ratio). For blocking experiments mice were pre-injected with 140μg of unlabelled ERIC1 into the tail vein 24 h prior 131I-ERIC1 application. Mice from these blocking experiments were measured after 72 h. Measurement of organ-specific radioactivity showed low organ-specific uptake (5.33 %ID/g after 72 h), which continuously decreased over the 96 hour

  2. Heavy chain only antibodies

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  3. Engineering antibody therapeutics.

    Science.gov (United States)

    Chiu, Mark L; Gilliland, Gary L

    2016-06-01

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

  4. Does Adhesive Resin Application Contribute to Resin Bond Durability on Etched and Silanized Feldspathic Ceramic?

    NARCIS (Netherlands)

    Passos, Sheila Pestana; Valandro, Luiz Felipe; Amaral, Regina; Ozcan, Mutlu; Bottino, Marco Antonio; Kimpara, Estevao Tomomitsu

    2008-01-01

    Purpose: To assess the effect of adhesive application and aging on the bond durability of resin cement to etched and silanized feldspathic ceramic. Materials and Methods: Twenty blocks (6.4 x 6.4 x 4.8 mm) of feldspathic ceramic (Vita VM7) were produced. The ceramic surfaces were conditioned with 10

  5. Growing Up with Their Blocks.

    Science.gov (United States)

    Winarski, Diana L.

    1995-01-01

    Describes one teacher's use of traditional wooden blocks in fifth-grade curriculum. Notes that use of blocks can teach communication, teamwork, precision, and arithmetic concepts. Also describes four easy classroom block projects. (TM)

  6. Capillarity-based switchable adhesion.

    Science.gov (United States)

    Vogel, Michael J; Steen, Paul H

    2010-02-23

    Drawing inspiration from the adhesion abilities of a leaf beetle found in nature, we have engineered a switchable adhesion device. The device combines two concepts: The surface tension force from a large number of small liquid bridges can be significant (capillarity-based adhesion) and these contacts can be quickly made or broken with electronic control (switchable). The device grabs or releases a substrate in a fraction of a second via a low-voltage pulse that drives electroosmotic flow. Energy consumption is minimal because both the grabbed and released states are stable equilibria that persist with no energy added to the system. Notably, the device maintains the integrity of an array of hundreds to thousands of distinct interfaces during active reconfiguration from droplets to bridges and back, despite the natural tendency of the liquid toward coalescence. We demonstrate the scaling of adhesion strength with the inverse of liquid contact size. This suggests that strengths approaching those of permanent bonding adhesives are possible as feature size is scaled down. In addition, controllability is fast and efficient because the attachment time and required voltage also scale down favorably. The device features compact size, no solid moving parts, and is made of common materials.

  7. Feasibility and constraints of particle targeting using the antigen-antibody interaction

    Science.gov (United States)

    Tokárová, Viola; Pittermannová, Anna; Král, Vlastimil; Řezáčová, Pavlína; Štěpánek, František

    2013-11-01

    This work is concerned with the surface modification of fluorescent silica nanoparticles by a monoclonal antibody (M75) and the specific bioadhesion of such particles to surfaces containing the PG domain of carbonic anhydrase IX (CA IX), which is a trans-membrane protein specifically expressed on the surfaces of several tumor cell lines. The adhesion strength of antibody-bearing silica nanoparticles to antigen-bearing surfaces was investigated under laminar flow conditions in a microfluidic cell and compared to the adhesion of unmodified silica nanoparticles and nanoparticles coupled with an unspecific antibody. Adhesion to cancer cells using flow cytometry was also investigated and in all cases the adhesion strength of M75-modified nanoparticles was significantly stronger than for the unmodified or unspecific nanoparticles, up to several orders of magnitude in some cases. The specific modification of nano- and microparticles by an antibody-like protein therefore appears to be a feasible approach for the targeting of tumor cells.This work is concerned with the surface modification of fluorescent silica nanoparticles by a monoclonal antibody (M75) and the specific bioadhesion of such particles to surfaces containing the PG domain of carbonic anhydrase IX (CA IX), which is a trans-membrane protein specifically expressed on the surfaces of several tumor cell lines. The adhesion strength of antibody-bearing silica nanoparticles to antigen-bearing surfaces was investigated under laminar flow conditions in a microfluidic cell and compared to the adhesion of unmodified silica nanoparticles and nanoparticles coupled with an unspecific antibody. Adhesion to cancer cells using flow cytometry was also investigated and in all cases the adhesion strength of M75-modified nanoparticles was significantly stronger than for the unmodified or unspecific nanoparticles, up to several orders of magnitude in some cases. The specific modification of nano- and microparticles by an antibody

  8. THE MECHANISM OF ANTI-IMPLANTATION EFFECT OF PROGESTERONE MONOCLONAL ANTIBODIES IN MICE

    Institute of Scientific and Technical Information of China (English)

    WANGMin-Yi; HEZhi-Ying; WANGHan-Zheng

    1989-01-01

    The purpose of this study is to investigate the mechanism by which antiprogcsterone monoclonal antibodies block early pregnancy in mice. The mechanism of passive immunization is a complex issue as indicated below:

  9. Comparing 14-day adhesive patch with 24-h Holter monitoring.

    Science.gov (United States)

    Cheung, Christopher C; Kerr, Charles R; Krahn, Andrew D

    2014-05-01

    Barrett PM, Komatireddy R, Haaser S et al. Comparison of 24-hour Holter monitoring with 14-day novel adhesive patch electrocardiographic monitoring. Am. J. Med. 127(1), 95.e11–95.e17 (2014). The investigation of cardiac arrhythmias in the outpatient ambulatory setting has traditionally been initiated with the Holter monitor. Using the continuous recording over 24 or 48 h, the Holter monitor permits the detection of baseline rhythm, dysrhythmia and conduction abnormalities, including heart block and changes in the ST segment that may indicate myocardial ischemia. However, apart from the bulkiness and inconvenience of the device itself, the lack of extended monitoring results in a diagnostic yield of typically less than 20%. In this study by Barrett et al., 146 patients referred for the evaluation of cardiac arrhythmia were prospectively enrolled to wear both the 24-h Holter monitor and 14-day adhesive patch monitor (Zio Patch) simultaneously. The primary outcome was the detection of any one of six arrhythmias: supraventricular tachycardia, atrial fibrillation/flutter, pause >3 s, atrioventricular block, ventricular tachycardia, or polymorphic ventricular tachycardia/fibrillation. The adhesive patch monitor detected more arrhythmia events compared with the Holter monitor over the total wear time (96 vs. 61 events; p Holter monitor detected more events during the initial 24-h monitoring period (61 vs. 52 events; p = 0.013). Novel, single-lead, intermediate-duration, user-friendly adhesive patch monitoring devices, such as the Zio Patch, represent the changing face of ambulatory ECG monitoring. However, the loss of quality, automated rhythm analysis and inability to detect myocardial ischemia continue to remain important issues that will need to be addressed prior to the implementation of these new devices.

  10. Macrophages are critical effectors of antibody therapies for cancer.

    Science.gov (United States)

    Weiskopf, Kipp; Weissman, Irving L

    2015-01-01

    Macrophages are innate immune cells that derive from circulating monocytes, reside in all tissues, and participate in many states of pathology. Macrophages play a dichotomous role in cancer, where they promote tumor growth but also serve as critical immune effectors of therapeutic antibodies. Macrophages express all classes of Fcγ receptors, and they have immense potential to destroy tumors via the process of antibody-dependent phagocytosis. A number of studies have demonstrated that macrophage phagocytosis is a major mechanism of action of many antibodies approved to treat cancer. Consequently, a number of approaches to augment macrophage responses to therapeutic antibodies are under investigation, including the exploration of new targets and development of antibodies with enhanced functions. For example, the interaction of CD47 with signal-regulatory protein α (SIRPα) serves as a myeloid-specific immune checkpoint that limits the response of macrophages to antibody therapies, and CD47-blocking agents overcome this barrier to augment phagocytosis. The response of macrophages to antibody therapies can also be enhanced with engineered Fc variants, bispecific antibodies, or antibody-drug conjugates. Macrophages have demonstrated success as effectors of cancer immunotherapy, and further investigation will unlock their full potential for the benefit of patients. PMID:25667985

  11. Detection of HBs antigen in routine paraffin embedded liver tissue by enzyme-labelled antibody technique

    Directory of Open Access Journals (Sweden)

    Tsuji,Takao

    1976-02-01

    Full Text Available HB surface antigen (HBs Ag was detected using the enzyme-labelled antibody technique on routinely processed liver biopsy material fixed in Bouin's fixative and embedded in paraffin. Of 85 examined specimens, 45 cases were HBs Ag positive by both the immunofluorescent test and the enzyme labelled antibody technique. The remaining 40 cases were negative by both techniques. The specificity of HBs Ag detected by the enzyme-labelled antibody technique was confirmed by the blocking test using guinea pig specific HBs antibody. The results indicate that the enzyme-labelled antibody technique may be useful for detecting HBs Ag on routine paraffin sections.

  12. Comparative study to evaluate shear bond strength of RMGIC to composite resin using different adhesive systems

    Directory of Open Access Journals (Sweden)

    Manoj G Chandak

    2012-01-01

    Full Text Available Aim: The aim of the study is to compare and evaluate the role of new dental adhesives to bond composite to the resinmodified glass inomer cement (RMGIC. Materials and Methods: Thirty specimens were prepared on acrylic blocks, with wells prepared in it by drilling holes, to retain the RMGIC. The specimens were randomly divided into three groups of ten specimens each. In Group a thin layer of selfetch adhesive (3M ESPE was applied between the RMGIC and the composite resin FILTEK P60 (3M SPE. In Group II, total etch adhesive (Adeper Scotch bond 2, 3M ESPE was applied, and in Group III, there was no application of any adhesive between RMGIC and the composite resin. After curing all the specimens, the shear bond strength was measured using an Instron universal testing machine. Results: The results were drawn and tabulated using ANOVA-fishers and Dunnet D statistical tests.The maximum shear bond strength values were recorded in Group I specimens with self-etch adhesive showing a mean value of 2.74 when compared to the Group II adhesive (Total etch showing a mean shear strength of value 1.89, where no adhesive was used, showed a minimum mean shear bond strength of 1.42. There was a great and significant difference between Group I and Group II (P value 0.05 whereas, both Group I and Group II showed a vast and significant difference from Group III (P value = 0-001. Conclusion: Hence, this present study concludes that application of self-etch adhesive (3M ESPE, U.S.A in between RMGIC and composite resin increases the shear bond strength between RMGIC and the resin composites, as compared to the total-etch type adhesive (Adeper Scotch bond 2,3M ESPE, U.S.A as well as without application of the adhesive agent.

  13. Development of syngeneic monoclonal anti-idiotype antibodies to mouse monoclonal anti-asialoglycoprotein receptor antibody.

    Directory of Open Access Journals (Sweden)

    Hirai M

    2002-06-01

    Full Text Available Anti-idiotype antibodies (Ab2 play an important role in the homeostasis of immune responses and are related to the development and the disease activity of certain autoimmune diseases. The asialoglycoprotein receptor (ASGPR is considered one of the target antigens in the pathogenesis of autoimmune chronic active hepatitis (AIH. We previously developed a mouse monoclonal antibody (clone 8D7 which recognizes rat and human ASGPR. In this study, to help investigate the anti-ASGPR antibody-anti-idiotype antibody network in patients with AIH, we developed a syngeneic mouse monoclonal Ab2 to the 8D7 anti-ASGPR antibody (Ab1. One clone, designated as 3C8, tested positive for specific reactivity to 8D7-Ab1 and did not bind to other irrelevant immunoglobulins. By competitive inhibition assays, the binding of 8D7-Ab1 to liver membrane extracts, i.e., the crude antigen preparation, was inhibited by 3C8-Ab2 in a dose-dependent manner, and the binding of 8D7-Ab1 to 3C8-Ab2 was inhibited by the liver membrane extracts. In the immunohistochemical analysis, 3C8-Ab2 blocked the specific staining of sinusoidal margins of rat hepatocytes by 8D7-Ab1. These results suggest that 3C8 anti-idiotype antibody recognizes the specific idiotypic determinants within the antigen-binding site of 8D7-Ab1.

  14. Tumor necrosis factor α antibody prevents brain damage of rats with acute necrotizing pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Yan-Ling Yang; Ji-Peng Li; Kai-Zong Li; Ke-Feng Dou

    2004-01-01

    AIM: To study the protective effects of tumor necrosis factor á (TNFα) antibody on pancreatic encephalopathy in rats.METHODS:One hundred and twenty SD rats were randomly divided into normal control group,acute necrotizing pancreatitis group and TNFα antibody treated group.Acute hemorrhage necrotizing pancreatitis model in rats was induced by retrograde injection of 50 g/L sodium taurocholate into the pancreatobiliary duct.Serum TNFα was detected and animals were killed 12 h after drug administration.Changes in content of brain water,MDA and SOD as well as leucocyte adhesion of brain microvessels were measured.RESULTS:In TNFα antibody treated group,serum TNFálevel was decreased.Content of brain water,MDA and SOD as well as leucocyte adhesion were decreased significantly in comparison with those of acute necrotizing pancreatitis group (P<0.05).CONCLUSION:TNFα antibody can alleviate the brain damage of rats with acute hemorrhage necrotizing pancreatitis.

  15. Changes in the Properties of the Thyrotropin Receptor Antibody in Patients with Graves’ Disease after Radioiodine Treatment

    OpenAIRE

    Cho, Bo Youn; Shong, Young Kee; Chung, June-Key; Lee, Myung Chul; Lee, Hong Kyu; Koh, Chang-Soon; Min, Hun Ki

    1990-01-01

    We investigated the effect of a single dose of 131I upon thyrotropin receptor antibodies (TRAb) in 21 patients with Graves’ disease. The thyrotropin receptor antibodies were assessed by parallel measurements of thyrotropin binding inhibitor immunoglobulin (TBII), thyroid stimulating antibody (TSAb) and thyroid stimulation blocking antibody (TSBAb) in serum by radoreceptor assay, stimulation of adenlate cyclase and inhibition of TSH-stimulated adenylate cyclase activation in FRTL-5 cells, resp...

  16. Block diagonal and schur complement preconditioners for block-toeplitz systems with small size blocks

    OpenAIRE

    Ching, WK; Ng, MK; Wen, YW

    2007-01-01

    In this paper we consider the solution of Hermitian positive definite block-Toeplitz systems with small size blocks. We propose and study block diagonal and Schur complement preconditioners for such block-Toeplitz matrices. We show that for some block-Toeplitz matrices, the spectra of the preconditioned matrices are uniformly bounded except for a fixed number of outliers where this fixed number depends only on the size of the block. Hence, conjugate gradient type methods, when applied to solv...

  17. Right bundle branch block

    DEFF Research Database (Denmark)

    Bussink, Barbara E; Holst, Anders Gaarsdal; Jespersen, Lasse;

    2013-01-01

    AimsTo determine the prevalence, predictors of newly acquired, and the prognostic value of right bundle branch block (RBBB) and incomplete RBBB (IRBBB) on a resting 12-lead electrocardiogram in men and women from the general population.Methods and resultsWe followed 18 441 participants included.......5%/2.3% in women, P Right bundle branch block was associated with significantly...... increased all-cause and cardiovascular mortality in both genders with age-adjusted hazard ratios (HR) of 1.31 [95% confidence interval (CI), 1.11-1.54] and 1.87 (95% CI, 1.48-2.36) in the gender pooled analysis with little attenuation after multiple adjustment. Right bundle branch block was associated...

  18. Bactericidal block copolymer micelles.

    Science.gov (United States)

    Vyhnalkova, Renata; Eisenberg, Adi; van de Ven, Theo

    2011-05-12

    Block copolymer micelles with bactericidal properties were designed to deactivate pathogens such as E. coli bacteria. The micelles of PS-b-PAA and PS-b-P4VP block copolymers were loaded with biocides TCMTB or TCN up to 20 or 30 wt.-%, depending on the type of antibacterial agent. Bacteria were exposed to loaded micelles and bacterial deactivation was evaluated. The micelles loaded with TCN are bactericidal; bacteria are killed in less than two minutes of exposure. The most likely interpretation of the data is that the biocide is transferred to the bacteria by repeated micelle/bacteria contacts, and not via the solution. PMID:21275041

  19. RBC Antibody Screen

    Science.gov (United States)

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

  20. [FTIR spectroscopic studies of facial prosthetic adhesives].

    Science.gov (United States)

    Kang, Biao; Yang, Qing-fang; Liang, Jian-feng; Zhao, Yi-min

    2008-10-01

    According to the composition of the traditional facial prosthetic adhesives, most of adhesives can be classified into two categories: acrylic polymer-based adhesive and silicone-based adhesive. In previous studies, measurements of various mechanical bond strengths were carried out, whereas the functional groups of the adhesives were evaluated seldom during the adhesion. In the present study the analysis of two facial prosthetic adhesives (Epithane and Secure Adhesive) was carried out by using infrared spectroscopy. Two adhesives in the form of fluid or semisolid were submitted to FTIR spectroscopy, respectively. The results showed that water and ammonia residue volatilized during the solidification of Epithane, and absorption peak reduction of carbonyl was due to the volatilization of acetate vinyl from Secure Adhesive. Similar silicone functional groups both in the silicone-based adhesive and in silicone elastomer could be the key to higher bond strength between silicone elastomer and skin with silicone-based adhesive. The position, shape of main absorption peaks of three adhesives didn't change, which showing that their main chemicals and basic structures didn't change during solidification. PMID:19123392

  1. Antibody to collapsin response mediator protein 1 promotes neurite outgrowth from rat hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Hongsheng Lin; Jing Chen; Wenbin Zhang; Xiaobing Gong; Biao Chen; Guoqing Guo

    2011-01-01

    This study examined the role of collapsin response mediator protein 1 (CRMP-1) on neurite outgrowth from rat hippocampal neurons by blocking its function using an antibody. Hippocampal neurons, cultured in vitro, were treated (blocked) using a polyclonal antibody to CRMP-1, and neurite outgrowth and cytoskeletal changes w ere captured using atomic force microscopy and laser confocal microscopy. Control cells, treated with normal rabbit IgG, established their characteristic morphology and had a large number of processes emerging from the soma, including numerous branches. Microtubules were clearly visible in the soma, formed an elaborate network, and were aligned in parallel arrays to form bundles which projected into neurites. After blocking with CRMP-1 antibody, the number of branches emerging from axons and dendrites significantly increased and were substantially longer, compared with control cells. However, the microtubule network nearly disappeared and only a few remnants were visible. When CRMP-1 antibody-blocked neurons were treated with the Rho inhibitor, Y27632, numerous neurites emerged from the soma, and branches were more abundant than in control neurons. Although the microtubules were not as clearly visible compared with neurons cultured in control medium, the microtubule network recovered in cells treated with Y27632, when compared with cells that were blocked by CRMP-1 antibody (but not treated with Y27632). These results demonstrate that neurite outgrowth from hippocampal neurons can be promoted by blocking CRMP-1 with a polyclonal antibody.

  2. E-Block: A Tangible Programming Tool with Graphical Blocks

    OpenAIRE

    Danli Wang; Yang Zhang; Shengyong Chen

    2013-01-01

    This paper designs a tangible programming tool, E-Block, for children aged 5 to 9 to experience the preliminary understanding of programming by building blocks. With embedded artificial intelligence, the tool defines the programming blocks with the sensors as the input and enables children to write programs to complete the tasks in the computer. The symbol on the programming block's surface is used to help children understanding the function of each block. The sequence information is transfer...

  3. Engagement of major histocompatibility complex class I and class II molecules up-regulates intercellular adhesion of human B cells via a CD11/CD18-independent mechanism.

    Science.gov (United States)

    Alcover, A; Juillard, V; Acuto, O

    1992-02-01

    We have studied the role of major histocompatibility complex (MHC) molecules in the regulation of intercellular adhesion of human B cells. We found that molecules able to bind to MHC class II molecules, such as monoclonal antibodies or staphylococcal enterotoxins, induced rapid and sustained homotypic adhesion of Epstein-Barr virus (EBV)-transformed B cell lines as well as peripheral blood B lymphocytes. Moreover, anti-MHC class I monoclonal antibodies also stimulated intercellular adherence. Adhesion induced upon MHC engagement was faster and stronger than that triggered by phorbol esters. It needed active metabolism, but divalent cations were not required. Monoclonal antibodies directed against LFA-1 (CD11a/CD18) or its ligand ICAM-1 (CD54) did not inhibit MHC class II-induced homotypic adhesion of various EBV-transformed B cell lines, nor of a variant of the B cell line Raji expressing very low LFA-1 surface levels. Moreover, EBV-transformed B cells from a severe lymphocyte adhesion deficiency patient, lacking surface CD11/CD18, also aggregated in response to anti-MHC class I or class II monoclonal antibodies. Together these data indicate that engagement of MHC molecules may transduce signals to B cells resulting in up-regulation of intercellular adhesion, via an LFA-1-independent mechanism. This may play a role in the stabilization of T cell/antigen-presenting cell conjugates at the moment of antigen recognition.

  4. Endoglin regulates mural cell adhesion in the circulatory system.

    Science.gov (United States)

    Rossi, Elisa; Smadja, David M; Boscolo, Elisa; Langa, Carmen; Arevalo, Miguel A; Pericacho, Miguel; Gamella-Pozuelo, Luis; Kauskot, Alexandre; Botella, Luisa M; Gaussem, Pascale; Bischoff, Joyce; Lopez-Novoa, José M; Bernabeu, Carmelo

    2016-04-01

    The circulatory system is walled off by different cell types, including vascular mural cells and podocytes. The interaction and interplay between endothelial cells (ECs) and mural cells, such as vascular smooth muscle cells or pericytes, play a pivotal role in vascular biology. Endoglin is an RGD-containing counter-receptor for β1 integrins and is highly expressed by ECs during angiogenesis. We find that the adhesion between vascular ECs and mural cells is enhanced by integrin activators and inhibited upon suppression of membrane endoglin or β1-integrin, as well as by addition of soluble endoglin (SolEng), anti-integrin α5β1 antibody or an RGD peptide. Analysis of different endoglin mutants, allowed the mapping of the endoglin RGD motif as involved in the adhesion process. In Eng (+/-) mice, a model for hereditary hemorrhagic telangectasia type 1, endoglin haploinsufficiency induces a pericyte-dependent increase in vascular permeability. Also, transgenic mice overexpressing SolEng, an animal model for preeclampsia, show podocyturia, suggesting that SolEng is responsible for podocytes detachment from glomerular capillaries. These results suggest a critical role for endoglin in integrin-mediated adhesion of mural cells and provide a better understanding on the mechanisms of vessel maturation in normal physiology as well as in pathologies such as preeclampsia or hereditary hemorrhagic telangiectasia.

  5. Complete congenital heart block in autoimmune hepatitis (SLA-positive).

    Science.gov (United States)

    Knolle, P; Mayet, W; Lohse, A W; Treichel, U; Meyer zum Büschenfelde, K H; Gerken, G

    1994-08-01

    Complete congenital heart block is a serious complication of neonatal lupus erythematosus which most often occurs in children of mothers suffering from connective tissue disease. We report the occurrence of complete congenital heart block associated with autoimmune hepatitis (SLA-positive). A 32-year-old woman was treated for more than 10 years for autoimmune hepatitis (SLA-/ANA-positive) and remained in clinical remission under immunosuppressive therapy. She showed an MHC-haplotype typical for autoimmune hepatitis (A1, B8, DR3). After a normal first pregnancy, an emergency caesarean section was performed in the 32nd week of her second pregnancy because of fetal bradycardia. The child died a few hours after delivery of complete congenital AV-block. Retrospective analysis of the maternal serum showed the emergence of SS-A/Ro-antibodies prior to the second pregnancy. The maternal serum antibodies were reactive with the 52 kD SS-A/Ro-antigen, as demonstrated by immunoblot employing recombinant SSA/Ro-antigen. The occurrence of complete congenital heart block has been shown to be associated with the presence of SS-A/Ro antibodies as well as the MHC-haplotype DR3. With respect to this genetic linkage, pregnant patients with autoimmune hepatitis and the MHC-haplotype DR3 should be examined for the presence of SS-A/Ro-antibodies. They should be closely followed during pregnancy to enable early detection of the development of congenital heart block, as prevention by plasmapheresis plus dexamethasone may be possible at an early stage.

  6. A Place for Block Play.

    Science.gov (United States)

    Moore, Gary T.

    1997-01-01

    Discusses the importance of block play--including its contributions to perceptual, fine motor, and cognitive development--and components of a good preschool block play area. Recommends unit blocks complemented by stacking blocks, toys, beads, cubes, and Brio wooden toys. Makes recommendations for space, size, locations and connections to other…

  7. Antibodies to West Nile Virus in Wild and Farmed Crocodiles in Southeastern Mexico

    OpenAIRE

    Machain-Williams, Carlos; Padilla-Paz, Sergio E.; Weber, Manuel; Cetina-Trejo, Rosa; Juarez-Ordaz, José Alfredo; Loroño-Pino, María Alba; Ulloa, Armando; Wang, Chong; Garcia-Rejon, Julián; Blitvich, Bradley J.

    2013-01-01

    Surveillance for evidence of West Nile virus (WNV) infection in Morelet’s crocodiles (Crocodylus moreletii) was conducted in Campeche State, Mexico, in 2007. Sera from 62 crocodiles (32 free-ranging and 30 captive) were assayed for antibodies to WNV by epitope-blocking enzyme-linked immunosorbent assay. Antibodies to WNV were detected in 13 (41%) wild and nine (30%) captive crocodiles, and the overall antibody prevalence was 35%. Although evidence of WNV infection in captive crocodiles has be...

  8. Candida biofilms: is adhesion sexy?

    Science.gov (United States)

    Soll, David R

    2008-08-26

    The development of Candida albicans biofilms requires two types of adhesion molecule - the Als proteins and Hwp1. Mutational analyses have recently revealed that these molecules play complementary roles, and their characteristics suggest that they may have evolved from primitive mating agglutinins. PMID:18727911

  9. Creep behaviour of flexible adhesives

    NARCIS (Netherlands)

    Straalen, IJ.J. van; Botter, E.; Berg, A. van den; Beers, P. van

    2004-01-01

    Since flexible adhesives are used more and more in structural applications, designers should have a better understanding of its behaviour under various conditions as ultimate load, fatigue load, long-term load and environmental conditions. This paper focuses on long-term load conditions and its effe

  10. Computational Chemistry of Adhesive Bonds

    Science.gov (United States)

    Phillips, Donald H.

    1999-01-01

    This investigation is intended to determine the electrical mechanical, and chemical properties of adhesive bonds at the molecular level. The initial determinations will be followed by investigations of the effects of environmental effects on the chemistry and properties of the bond layer.

  11. Selection of Recombinant Human Antibodies.

    Science.gov (United States)

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

    2016-01-01

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

  12. Anti-insulin antibody test

    Science.gov (United States)

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

  13. Adhesion of biocompatible and biodegradable micropatterned surfaces

    NARCIS (Netherlands)

    Kaiser, J.S.; Kamperman, M.M.G.; Souza, E.J.; Schick, B.; Arzt, E.

    2011-01-01

    We studied the effects of pillar dimensions and stiffness of biocompatible and biodegradable micropatterned surfaces on adhesion on different compliant substrates. The micropatterned adhesives were based on biocompatible polydimethylsiloxane (PDMS) and biodegradable poly(lactic-co-glycolic) acid (PL

  14. Focal adhesions and cell-matrix interactions

    DEFF Research Database (Denmark)

    Woods, A; Couchman, J R

    1988-01-01

    Focal adhesions are areas of cell surfaces where specializations of cytoskeletal, membrane and extracellular components combine to produce stable cell-matrix interactions. The morphology of these adhesions and the components identified in them are discussed together with possible mechanisms...

  15. Effects of Block Scheduling

    Directory of Open Access Journals (Sweden)

    William R. Veal

    1999-09-01

    Full Text Available This study examined the effects of a tri-schedule on the academic achievement of students in a high school. The tri-schedule consists of traditional, 4x4 block, and hybrid schedules running at the same time in the same high school. Effectiveness of the schedules was determined from the state mandated test of basic skills in reading, language, and mathematics. Students who were in a particular schedule their freshman year were tested at the beginning of their sophomore year. A statistical ANCOVA test was performed using the schedule types as independent variables and cognitive skill index and GPA as covariates. For reading and language, there was no statistically significant difference in test results. There was a statistical difference mathematics-computation. Block mathematics is an ideal format for obtaining more credits in mathematics, but the block format does little for mathematics achievement and conceptual understanding. The results have content specific implications for schools, administrations, and school boards who are considering block scheduling adoption.

  16. Spice Blocks Melanoma Growth

    Science.gov (United States)

    Science Teacher, 2005

    2005-01-01

    Curcumin, the pungent yellow spice found in both turmeric and curry powders, blocks a key biological pathway needed for development of melanoma and other cancers, according to a study that appears in the journal Cancer. Researchers from The University of Texas M. D. Anderson Cancer Center demonstrate how curcumin stops laboratory strains of…

  17. Contaminated soil concrete blocks

    NARCIS (Netherlands)

    Korte, de A.C.J.; Brouwers, H.J.H.; Limbachiya, Mukesh C.; Kew, Hsein Y.

    2009-01-01

    According to Dutch law the contaminated soil needs to be remediated or immobilised. The main focus in this article is the design of concrete blocks, containing contaminated soil, that are suitable for large production, financial feasible and meets all technical and environmental requirements. In ord

  18. Edit Distance with Block Deletions

    OpenAIRE

    Dana Shapira; Storer, James A.

    2011-01-01

    Several variants of the edit distance problem with block deletions are considered. Polynomial time optimal algorithms are presented for the edit distance with block deletions allowing character insertions and character moves, but without block moves. We show that the edit distance with block moves and block deletions is NP-complete (Nondeterministic Polynomial time problems in which any given solution to such problem can be verified in polynomial time, and any NP problem can be converted into...

  19. Fermion-Scalar Conformal Blocks

    CERN Document Server

    Iliesiu, Luca; Poland, David; Pufu, Silviu S; Simmons-Duffin, David; Yacoby, Ran

    2015-01-01

    We compute the conformal blocks associated with scalar-scalar-fermion-fermion 4-point functions in 3D CFTs. Together with the known scalar conformal blocks, our result completes the task of determining the so-called `seed blocks' in three dimensions. Conformal blocks associated with 4-point functions of operators with arbitrary spins can now be determined from these seed blocks by using known differential operators.

  20. Lipid Raft is required for PSGL-1 ligation induced HL-60 cell adhesion on ICAM-1.

    Directory of Open Access Journals (Sweden)

    Tingshuang Xu

    Full Text Available P-selectin glycoprotein ligand-1 (PSGL-1 and integrins are adhesion molecules that play critical roles in host defense and innate immunity. PSGL-1 mediates leukocyte rolling and primes leukocytes for integrin-mediated adhesion. However, the mechanism that PSGL-1 as a rolling receptor in regulating integrin activation has not been well characterized. Here, we investigate the function of lipid raft in regulating PSGL-1 induced β2 integrin-mediated HL-60 cells adhesion. PSGL-1 ligation with antibody enhances the β2 integrin activation and β2 integrin-dependent adhesion to ICAM-1. Importantly, with the treatment of methyl-β-cyclodextrin (MβCD, we confirm the role of lipid raft in regulating the activation of β2 integrin. Furthermore, we find that the protein level of PSGL-1 decreased in raft fractions in MβCD treated cells. PSGL-1 ligation induces the recruitment of spleen tyrosine kinase (Syk, a tyrosine kinase and Vav1 (the pivotal downstream effector of Syk signaling pathway involved in cytoskeleton regulation to lipid raft. Inhibition of Syk activity with pharmacologic inhibitor strongly reduces HL-60 cells adhesion, implicating Syk is crucial for PSGL-1 mediated β2 integrin activation. Taken together, we report that ligation of PSGL-1 on HL-60 cells activates β2 integrin, for which lipid raft integrity and Syk activation are responsible. These findings have shed new light on the mechanisms that connect leukocyte initial rolling with subsequent adhesion.

  1. Vascular Endothelial-Cadherin Regulates Cytoskeletal Tension, Cell Spreading, and Focal Adhesions by Stimulating RhoAD⃞

    Science.gov (United States)

    Nelson, Celeste M.; Pirone, Dana M.; Tan, John L.; Chen, Christopher S.

    2004-01-01

    Changes in vascular endothelial (VE)-cadherin–mediated cell-cell adhesion and integrin-mediated cell-matrix adhesion coordinate to affect the physical and mechanical rearrangements of the endothelium, although the mechanisms for such cross talk remain undefined. Herein, we describe the regulation of focal adhesion formation and cytoskeletal tension by intercellular VE-cadherin engagement, and the molecular mechanism by which this occurs. Increasing the density of endothelial cells to increase cell-cell contact decreased focal adhesions by decreasing cell spreading. This contact inhibition of cell spreading was blocked by disrupting VE-cadherin engagement with an adenovirus encoding dominant negative VE-cadherin. When changes in cell spreading were prevented by culturing cells on a micropatterned substrate, VE-cadherin–mediated cell-cell contact paradoxically increased focal adhesion formation. We show that VE-cadherin engagement mediates each of these effects by inducing both a transient and sustained activation of RhoA. Both the increase and decrease in cell-matrix adhesion were blocked by disrupting intracellular tension and signaling through the Rho-ROCK pathway. In all, these findings demonstrate that VE-cadherin signals through RhoA and the actin cytoskeleton to cross talk with cell-matrix adhesion and thereby define a novel pathway by which cell-cell contact alters the global mechanical and functional state of cells. PMID:15075376

  2. Film adhesion in amorphous silicon solar cells

    Indian Academy of Sciences (India)

    A R M Yusoff; M N Syahrul; K Henkel

    2007-08-01

    A major issue encountered during fabrication of triple junction -Si solar cells on polyimide substrates is the adhesion of the solar cell thin films to the substrates. Here, we present our study of film adhesion in amorphous silicon solar cells made on different polyimide substrates (Kapton VN, Upilex-S and Gouldflex), and the effect of tie coats on film adhesion.

  3. Self-Adjustable Adhesion of Polyampholyte Hydrogels.

    Science.gov (United States)

    Roy, Chanchal Kumar; Guo, Hong Lei; Sun, Tao Lin; Ihsan, Abu Bin; Kurokawa, Takayuki; Takahata, Masakazu; Nonoyama, Takayuki; Nakajima, Tasuku; Gong, Jian Ping

    2015-12-01

    Developing nonspecific, fast, and strong adhesives that can glue hydrogels and biotissues substantially promotes the application of hydrogels as biomaterials. Inspired by the ubiquitous adhesiveness of bacteria, it is reported that neutral polyampholyte hydrogels, through their self-adjustable surface, can show rapid, strong, and reversible adhesion to charged hydrogels and biological tissues through the Coulombic interaction.

  4. ICAM-1-independent, CD18-dependent adhesion between neutrophils and human epithelial cells exposed in vitro to ozone

    Energy Technology Data Exchange (ETDEWEB)

    Tosi, M.F.; Hamedani, A.; Brosovich, J.; Alpert, S.E. (Case Western Reserve Univ. School of Medicine, Cleveland, OH (United States))

    1994-02-15

    Inhalant exposure to ozone can cause diffuse airway epithelial injury that is associated with an inflammatory response, including the influx of neutrophils into lung and airway tissue. The authors have previously documented enhanced adhesiveness by neutrophils for human airway epithelial cells in in vitro models of diseases associated with airway inflammation and have suggested that this enhanced adhesion may contribute to neutrophil-mediated airway injury. When primary human tracheal epithelial cell (TEC) monolayers were exposed to ozone at 2.0 ppm for 30 min or 0.5 ppm for 2 h, the percentage of PMN adhering to these cells increased from <5% to a maximum of approximately 75% by 18 to 24 h after the ozone exposure. No change was observed within the first 2 h after ozone exposure, but there was a statistically significant increase in PMN adhesion by 8 h after exposure. In contrast to previous studies with cytokine exposure or respiratory virus infection of TEC, the increased adhesion after ozone exposure was not associated with an increase in epithelial expression of ICAM-1. Consistent with the lack of induction of ICAM-1 by ozone exposure was the observation that anti-ICAM-1 mAbs previously shown to block PMN adhesion to TEC with increased ICAM-1 expression had no effect on PMN adhesion to ozone-exposed TEC. However, mAbs against CD11b or CD18 on PMN blocked PMN adhesion to ozone-exposed TEC by approximately 55 and 80%, respectively. Chemoattractant preactivation of PMN was necessary to achieve the highest levels of adhesion to ozone-treated TEC, in marked contrast to earlier studies with PMN adhesion to cytokine-treated or virus-infected TEC in which resting and prestimulated PMN exhibited the same high levels of adhesion.

  5. Block copolymer/homopolymer dual-layer hollow fiber membranes

    KAUST Repository

    Hilke, Roland

    2014-12-01

    We manufactured the first time block copolymer dual-layer hollow fiber membranes and dual layer flat sheet membranes manufactured by double solution casting and phase inversion in water. The support porous layer was based on polystyrene and the selective layer with isopores was formed by micelle assembly of polystyrene-. b-poly-4-vinyl pyridine. The dual layers had an excellent interfacial adhesion and pore interconnectivity. The dual membranes showed pH response behavior like single layer block copolymer membranes with a low flux for pH values less than 3, a fast increase between pH4 and pH6 and a constant high flux level for pH values above 7. The dry/wet spinning process was optimized to produce dual layer hollow fiber membranes with polystyrene internal support layer and a shell block copolymer selective layer.

  6. Effect of the application of a casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) paste and adhesive systems on bond durability of a fissure sealant.

    Science.gov (United States)

    Borges, Boniek Castillo Dutra; Catelan, Anderson; Sasaki, Robson Tetsuo; Ambrosano, Gláucia Maria Bovi; Reis, André Figueiredo; Aguiar, Flávio Henrique Baggio

    2013-01-01

    This study aimed to evaluate the effect of the previous application of a casein phosphopeptide-amorphous calcium phosphate paste (MI Paste, MI) and adhesive systems on the bond durability of a fissure sealant. Ninety-eight enamel blocks were obtained from proximal surfaces of erupted third molars. Specimens were divided into 14 groups (n = 7) according to the previous application of MI (with and without) and the adhesive systems used (no adhesive system; hydrophobic resin of a three-step etch-and-rinse adhesive system; etch-and-rinse single-bottle adhesive system; all-in-one adhesive system; two-step self-etching adhesive system; additional phosphoric acid conditioning and all-in-one adhesive system; additional phosphoric acid conditioning and two-step self-etching adhesive system). A fissure sealant (Fluroshield) was applied and photoactivated for 20 s. Beams (~0.7 mm(2)) were prepared for the microtensile bond strength test, which was executed after 24 h or 6 months of water storage. Fractured specimens were analyzed by scanning electronic microscopy. Data were analyzed by two-way ANOVA with repeated measures/Tukey's test (P adhesive systems presented higher means than those groups where MI was not applied. Higher frequency of cohesive failures was observed for groups with MI. Applying a CPP-ACP containing paste on enamel before adhesive systems was an effective method to increase bond durability of the sealant tested.

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

    Directory of Open Access Journals (Sweden)

    Sharad P Adekar

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

  8. Pulmonary biology of anti-interleukin 5 antibodies

    Directory of Open Access Journals (Sweden)

    Egan RW

    1997-01-01

    Full Text Available Interleukin 5 (IL-5 is a critical cytokine for the maturation of eosinophil precursors to eosinophils in the bone marrow and those eosinophils then accumulate in the lungs during asthma. We have studied anti IL-5 antibodies on allergic responses in mice, guinea pigs and monkeys and are extending this experiment into humans with a humanized antibody. In a monkey model of pulmonary inflammation and airway hyperreactivity, we found that the TRFK-5 antibody blocked both responses for three months following a single dose of 0.3 mg/kg, i.v. This antibody also blocked lung eosinophilia in mice by inhibiting release from the bone marrow. To facilitate multiple dosing and to reduce immunogenicity in humans, we prepared Sch 55700, a humanized antibody against IL-5. Sch 55700 was also active against lung eosinophilia in allergic monkeys and mice and against pulmonary eosinophilia and airway hyperresponsiveness in guinea pigs. Furthermore, as opposed to steroids, Sch 55700 did not cause immunosuppression in guinea pigs. Studies with this antibody in humans will be critical to establishing the therapeutic potential of IL-5 inhibition.

  9. Osteocyte apoptosis regulates osteoclast precursor adhesion via osteocytic IL-6 secretion and endothelial ICAM-1 expression.

    Science.gov (United States)

    Cheung, Wing-Yee; Simmons, Craig A; You, Lidan

    2012-01-01

    Osteocyte apoptosis precedes osteoclast resorption, and may act as a critical signal to trigger bone remodeling. While osteoclast precursors are known to travel via the circulation, the specific mechanisms by which they accumulate at remodeling sites are unclear. We hypothesized that osteocyte apoptosis mediates osteoclast precursor adhesion to vascular endothelium by regulating osteocytic secretion of IL-6 and soluble IL-6 receptor (sIL-6R) to promote endothelial ICAM-1 expression. We found that conditioned media from TNF-α-induced apoptotic MLO-Y4 osteocytes promoted RAW264.7 osteoclast precursor adhesion onto D4T endothelial cells (P<0.05). Blocking osteocyte apoptosis with a pan-caspase inhibitor (ZVAD-FMK) reduced osteoclast precursor adhesion to baseline levels (P<0.001). Endothelial cells treated with apoptotic osteocyte conditioned media had elevated surface expression of ICAM-1 (P<0.05), and blocking ICAM-1 abolished apoptosis-induced osteoclast precursor adhesion. Apoptotic osteocyte conditioned media contained more IL-6 (P<0.05) and sIL-6R (P<0.05) than non-apoptotic osteocyte conditioned media. When added exogenously, both IL-6 and sIL-6R were required for endothelial activation, and blocking IL-6 reduced apoptosis-induced osteoclast precursor adhesion to baseline levels (P<0.05). Therefore, we conclude that osteocyte apoptosis can promote osteoclast precursor adhesion to endothelial cells via ICAM-1; this is likely through increased osteocytic IL-6 and sIL-6R secretion, both of which are indispensible to endothelial activation. PMID:21986000

  10. NCCN Evidence Blocks.

    Science.gov (United States)

    Carlson, Robert W; Jonasch, Eric

    2016-05-01

    NCCN has developed a series of Evidence Blocks: graphics that provide ratings for each recommended treatment regimen in terms of efficacy, toxicity, quality and consistency of the supporting data, and affordability. The NCCN Evidence Blocks are currently available in 10 tumor types within the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). At a glance, patients and providers can understand how a given treatment was assessed by the NCCN Guidelines Panel and get a sense of how a given treatment may match individual needs and preferences. Robert W. Carlson, MD, CEO of NCCN, described the reasoning behind this new feature and how the tool is used, and Eric Jonasch, MD, Professor of Genitourinary Medical Oncology at The University of Texas MD Anderson Cancer Center, and Vice Chair of the NCCN Kidney Cancer Panel, described its applicability in the management of metastatic renal cell carcinoma. PMID:27226499

  11. Neuropeptides, via specific receptors, regulate T cell adhesion to fibronectin.

    Science.gov (United States)

    Levite, M; Cahalon, L; Hershkoviz, R; Steinman, L; Lider, O

    1998-01-15

    The ability of T cells to adhere to and interact with components of the blood vessel walls and the extracellular matrix is essential for their extravasation and migration into inflamed sites. We have found that the beta1 integrin-mediated adhesion of resting human T cells to fibronectin, a major glycoprotein component of the extracellular matrix, is induced by physiologic concentrations of three neuropeptides: calcitonin gene-related protein (CGRP), neuropeptide Y, and somatostatin; each acts via its own specific receptor on the T cell membrane. In contrast, substance P (SP), which coexists with CGRP in the majority of peripheral endings of sensory nerves, including those innervating the lymphoid organs, blocks T cell adhesion to fibronectin when induced by CGRP, neuropeptide Y, somatostatin, macrophage inflammatory protein-1beta, and PMA. Inhibition of T cell adhesion was obtained both by the intact SP peptide and by its 1-4 N-terminal and its 4-11, 5-11, and 6-11 C-terminal fragments, used at similar nanomolar concentrations. The inhibitory effects of the parent SP peptide and its fragments were abrogated by an SP NK-1 receptor antagonist, suggesting they all act through the same SP NK-1 receptor. These findings suggest that neuropeptides, by activating their specific T cell-expressed receptors, can provide the T cells with both positive (proadhesive) and negative (antiadhesive) signals and thereby regulate their function. Thus, neuropeptides may influence diverse physiologic processes involving integrins, including leukocyte-mediated migration and inflammation. PMID:9551939

  12. SUPERFICIAL CERVICAL PLEXUS BLOCK

    Directory of Open Access Journals (Sweden)

    Komang Mega Puspadisari

    2014-01-01

    Full Text Available Superficial cervical plexus block is one of the regional anesthesia in  neck were limited to thesuperficial fascia. Anesthesia is used to relieve pain caused either during or after the surgery iscompleted. This technique can be done by landmark or with ultrasound guiding. The midpointof posterior border of the Sternocleidomastoid was identified and the prosedure done on thatplace or on the level of cartilage cricoid.

  13. Neutrophil transmigration under shear flow conditions in vitro is junctional adhesion molecule-C independent.

    Science.gov (United States)

    Sircar, Monica; Bradfield, Paul F; Aurrand-Lions, Michel; Fish, Richard J; Alcaide, Pilar; Yang, Lin; Newton, Gail; Lamont, Deanna; Sehrawat, Seema; Mayadas, Tanya; Liang, Tony W; Parkos, Charles A; Imhof, Beat A; Luscinskas, Francis W

    2007-05-01

    Endothelial cell junctional adhesion molecule (JAM)-C has been proposed to regulate neutrophil migration. In the current study, we used function-blocking mAbs against human JAM-C to determine its role in human leukocyte adhesion and transendothelial cell migration under flow conditions. JAM-C surface expression in HUVEC was uniformly low, and treatment with inflammatory cytokines TNF-alpha, IL-1beta, or LPS did not increase its surface expression as assessed by FACS analysis. By immunofluorescence microscopy, JAM-C staining showed sparse localization to cell-cell junctions on resting or cytokine-activated HUVEC. Surprisingly, staining of detergent-permeabilized HUVEC revealed a large intracellular pool of JAM-C that showed little colocalization with von Willebrand factor. Adhesion studies in an in vitro flow model showed that functional blocking JAM-C mAb alone had no inhibitory effect on polymorphonuclear leukocyte (PMN) adhesion or transmigration, whereas mAb to ICAM-1 significantly reduced transmigration. Interestingly, JAM-C-blocking mAbs synergized with a combination of PECAM-1, ICAM-1, and CD99-blocking mAbs to inhibit PMN transmigration. Overexpression of JAM-C by infection with a lentivirus JAM-C GFP fusion protein did not increase adhesion or extent of transmigration of PMN or evoke a role for JAM-C in transendothelial migration. These data suggest that JAM-C has a minimal role, if any, in PMN transmigration in this model and that ICAM-1 is the preferred endothelial-expressed ligand for PMN beta(2) integrins during transendothelial migration. PMID:17442972

  14. HIV Antibody Test

    Science.gov (United States)

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

  15. Antinuclear antibody panel

    Science.gov (United States)

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

  16. Anti-cartilage antibody.

    Science.gov (United States)

    Greenbury, C L; Skingle, J

    1979-08-01

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

  17. Managing access block.

    Science.gov (United States)

    Cameron, Peter; Scown, Paul; Campbell, Donald

    2002-01-01

    There is pessimism regarding the ability of the Acute Health Sector to manage access block for emergency and elective patients. Melbourne Health suffered an acute bed crisis in 2001 resulting in record ambulance diversions and emergency department (ED) delays. We conducted an observational study to reduce access block for emergency patients whilst maintaining elective throughput at Melbourne Health. This involved a clinician-led taskforce using previously proven principles for organisational change to implement 51 actions to improve patient access over a three-month period. The primary outcome measures were ambulance diversion, emergency patients waiting more than 12 hours for an inpatient bed, elective throughput and theatre cancellations. Despite a reduction in multi-day bed numbers all primary objectives were met, ambulance diversion decreased to minimal levels, 12-hour waits decreased by 40% and elective throughput was maintained. Theatre cancellations were also minimised. We conclude that access block can be improved by clinician-led implementation of proven process improvements over a short time frame. The ability to sustain change over the longer term requires further study.

  18. Shift in epitope dominance of IgM and IgG responses to Plasmodium falciparum MSP1 block 4

    Directory of Open Access Journals (Sweden)

    Leke Rose GF

    2010-01-01

    Full Text Available Abstract Background Plasmodium falciparum merozoite surface protein-1 (MSP1 has been extensively studied as a blood-stage malaria vaccine candidate, with most work focused on the conserved 19 kDa and semi-conserved 42 kDa C-terminal regions (blocks 16-17 and the hypervariable N-terminal repeat region (block 2. However, recent genotyping studies suggest that additional regions of MSP1 may be under selective pressure, including a locus of intragenic recombination designated as block 4 within the 3' region of the gene. Methods The current study examined the antibody response to the two parental and two recombinant forms of block 4 and to blocks 16-17 (3D7 in study populations from Colombia, Papua New Guinea and Cameroon that differ in malaria transmission intensity and ethnic composition. Results IgM and IgG antibodies were detected against parental and recombinant MSP1 block 4 peptides in all three populations. Overall, 32-44% of the individuals produced IgM to one or more of the peptides, with most individuals having IgM antibodies reactive with both parental and recombinant forms. In contrast, IgG seropositivity to block 4 varied among populations (range 15-65%, with the majority of antibodies showing specificity for one or a pair of block 4 peptides. The IgG response to block 4 was significantly lower than that to blocks 16-17, indicating block 4 is subdominant. Antibodies to block 4 and blocks 16-17 displayed distinct IgG subclass biases, with block 4 responses biased toward IgG3 and blocks 16-17 toward IgG1. These patterns of responsiveness were consistently observed in the three study populations. Conclusions Production of antibodies specific for each parental and recombinant MSP1 block 4 allele in different populations exposed to P. falciparum is consistent with balancing selection of the MSP1 block 4 region by the immune response of individuals in areas of both low and high malaria transmission. MSP1 block 4 determinants may be important

  19. Future of petroleum-based adhesives polymers and tackifiers

    Energy Technology Data Exchange (ETDEWEB)

    De Stefano, J.M. [De Witt and Company, Venice, FL (United States)

    1995-12-31

    The growth of the adhesives business rests with the continuing availability of petroleum derived styrenic copolymers and hydrocarbon resin tackifiers. Within the past year, the styrene block copolymer market has gone ballistic due to an accident at one supplier plant and a delayed start-up at another. While there is a near-adequate supply of some copolymers, there is concern about the long term availability of the more popular styrene-isoprene-styrene (SIS) grades used in hot-melt adhesive formulations. Styrene may be tight at this moment but it will always be available because of its broad product base and favorable profit margin. However, the availability of isoprene, the key comonomer in SIS production, is very tight and prices are increasing. To a lesser degree, but equally important is the availability of suitable tackifying resins that are uniquely compatible with SIS. Currently these tackifiers are based on piperylene and cyclopentadiene feed stock. All three products; isoprene, piperylene and cyclopentadiene are pentadiene by-products produced in the dehydrogenation of ethane to ethylene. Ethylene is the most important petrochemical product in the world today. It drives the petrochemical industry. The objective of this paper is to help chemists and their managers understand the critical linkage of pentadiene building blocks with the macro-supply trains in the petrochemical and fuel industries.

  20. E-Block: A Tangible Programming Tool with Graphical Blocks

    Directory of Open Access Journals (Sweden)

    Danli Wang

    2013-01-01

    Full Text Available This paper designs a tangible programming tool, E-Block, for children aged 5 to 9 to experience the preliminary understanding of programming by building blocks. With embedded artificial intelligence, the tool defines the programming blocks with the sensors as the input and enables children to write programs to complete the tasks in the computer. The symbol on the programming block's surface is used to help children understanding the function of each block. The sequence information is transferred to computer by microcomputers and then translated into semantic information. The system applies wireless and infrared technologies and provides user with feedbacks on both screen and programming blocks. Preliminary user studies using observation and user interview methods are shown for E-Block's prototype. The test results prove that E-Block is attractive to children and easy to learn and use. The project also highlights potential advantages of using single chip microcomputer (SCM technology to develop tangible programming tools for children.

  1. Antibody tumor penetration

    Science.gov (United States)

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

    2009-01-01

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

  2. Expression of Recombinant Antibodies

    OpenAIRE

    Frenzel, André; Hust, Michael; Schirrmann, Thomas

    2013-01-01

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

  3. Inhibition of human immunodeficiency virus (HIV) infection in vitro by anticarbohydrate monoclonal antibodies

    DEFF Research Database (Denmark)

    Hansen, J E; Clausen, H; Nielsen, C;

    1990-01-01

    Carbohydrate structures are often involved in the initial adhesion of pathogens to target cells. In the present study, a panel of anticarbohydrate monoclonal antibodies (MAbs) was tested for their ability to inhibit in vitro human immunodeficiency virus infectivity. MAbs against three different N...

  4. Photochemical tissue bonding with chitosan adhesive films

    Directory of Open Access Journals (Sweden)

    Piller Sabine C

    2010-09-01

    Full Text Available Abstract Background Photochemical tissue bonding (PTB is a promising sutureless technique for tissue repair. PTB is often achieved by applying a solution of rose bengal (RB between two tissue edges, which are irradiated by a green laser to crosslink collagen fibers with minimal heat production. In this study, RB has been incorporated in chitosan films to create a novel tissue adhesive that is laser-activated. Methods Adhesive films, based on chitosan and containing ~0.1 wt% RB were manufactured and bonded to calf intestine by a solid state laser (λ = 532 nm, Fluence~110 J/cm2, spot size~0.5 cm. A single-column tensiometer, interfaced with a personal computer, tested the bonding strength. K-type thermocouples recorded the temperature (T at the adhesive-tissue interface during laser irradiation. Human fibroblasts were also seeded on the adhesive and cultured for 48 hours to assess cell growth. Results The RB-chitosan adhesive bonded firmly to the intestine with adhesion strength of 15 ± 2 kPa, (n = 31. The adhesion strength dropped to 0.5 ± 0.1 (n = 8 kPa when the laser was not applied to the adhesive. The average temperature of the adhesive increased from 26°C to 32°C during laser exposure. Fibroblasts grew confluent on the adhesive without morphological changes. Conclusion A new biocompatible chitosan adhesive has been developed that bonds photochemically to tissue with minimal temperature increase.

  5. Gecko adhesion pad: a smart surface?

    Science.gov (United States)

    Pesika, Noshir S.; Zeng, Hongbo; Kristiansen, Kai; Zhao, Boxin; Tian, Yu; Autumn, Kellar; Israelachvili, Jacob

    2009-11-01

    Recently, it has been shown that humidity can increase the adhesion of the spatula pads that form the outermost (adhesive) surface of the tokay gecko feet by 50% relative to the main adhesion mechanism (i.e. van der Waals adhesive forces), although the mechanism by which the enhancement is realized is still not well understood. A change in the surface hydrophobicity of a gecko setal array is observed when the array, which supports the spatulae, is exposed to a water drop for more than 20 min, suggesting a change in the hydrophilic-lyophilic balance (HLB), and therefore of the conformation of the surface proteins. A surface force apparatus (SFA) was used to quantify these changes, i.e. in the adhesion and friction forces, while shearing the setal array against a silica surface under (i) dry conditions, (ii) 100% humidity and (iii) when fully immersed in water. The adhesion increased in the humid environment but greatly diminished in water. Although the adhesion forces changed significantly, the friction forces remained unaffected, indicating that the friction between these highly textured surfaces is 'load-controlled' rather than 'adhesion-controlled'. These results demonstrate that the gecko adhesive pads have the ability to exploit environmental conditions to maximize their adhesion and stabilize their friction forces. Future designs of synthetic dry adhesives inspired by the gecko can potentially include similar 'smart' surfaces that adapt to their environment.

  6. Gecko adhesion pad: a smart surface?

    Energy Technology Data Exchange (ETDEWEB)

    Pesika, Noshir S [Chemical and Biomolecular Engineering Department, Tulane University, New Orleans, LA 70118 (United States); Zeng Hongbo [Chemical and Materials Engineering Department, University of Alberta, Edmonton, AB, T6G 2V4 (Canada); Kristiansen, Kai; Israelachvili, Jacob [Chemical Engineering Department, University of California, Santa Barbara, CA 93117 (United States); Zhao, Boxin [Chemical Engineering Department and Waterloo Institute of Nanotechnology, University of Waterloo, Ontario, N2L 3G1 (Canada); Tian Yu [State Key Laboratory of Tribology, Department of Precision Instruments, Tsinghua University, Beijing 100084 (China); Autumn, Kellar, E-mail: npesika@tulane.ed [Department of Biology, Lewis and Clark College, Portland, OR 97219 (United States)

    2009-11-18

    Recently, it has been shown that humidity can increase the adhesion of the spatula pads that form the outermost (adhesive) surface of the tokay gecko feet by 50% relative to the main adhesion mechanism (i.e. van der Waals adhesive forces), although the mechanism by which the enhancement is realized is still not well understood. A change in the surface hydrophobicity of a gecko setal array is observed when the array, which supports the spatulae, is exposed to a water drop for more than 20 min, suggesting a change in the hydrophilic-lyophilic balance (HLB), and therefore of the conformation of the surface proteins. A surface force apparatus (SFA) was used to quantify these changes, i.e. in the adhesion and friction forces, while shearing the setal array against a silica surface under (i) dry conditions, (ii) 100% humidity and (iii) when fully immersed in water. The adhesion increased in the humid environment but greatly diminished in water. Although the adhesion forces changed significantly, the friction forces remained unaffected, indicating that the friction between these highly textured surfaces is 'load-controlled' rather than 'adhesion-controlled'. These results demonstrate that the gecko adhesive pads have the ability to exploit environmental conditions to maximize their adhesion and stabilize their friction forces. Future designs of synthetic dry adhesives inspired by the gecko can potentially include similar 'smart' surfaces that adapt to their environment.

  7. Integrin engagement mediates tyrosine dephosphorylation on platelet-endothelial cell adhesion molecule 1.

    OpenAIRE

    Lu, T T; Yan, L G; Madri, J. A.

    1996-01-01

    Platelet-endothelial cell adhesion molecule 1 (PECAM-1, CD31) is a 130-kDa member of the immunoglobulin gene superfamily expressed on endothelial cells, platelets, neutrophils, and monocytes and plays a role during endothelial cell migration. Phosphoamino acid analysis and Western blot analysis with anti-phosphotyrosine antibody show that endothelial PECAM-1 is tyrosine-phosphorylated. Phosphorylation is decreased with endothelial cell migration on fibronectin and collagen and with cell sprea...

  8. Early adhesive behavior of bone-marrow-derived mesenchymal stem cells on collagen electrospun fibers

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Casey K; Liao, Susan; Lareu, Ricky R; Raghunath, Michael [Division of Bioengineering, National University of Singapore, 7 Engineering Drive 1, Singapore 117574 (Singapore); Li, Bojun; Ramakrishna, S [Nanoscience and Nanotechnology Initiative, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Larrick, James W, E-mail: doschanc@nus.edu.s [Panorama Research Institute, 2462 Wyandotte Street, Mountain View, CA 94043 (United States)

    2009-06-15

    A bioabsorbable nanofibrous scaffold was developed for early adhesion of mesenchymal stem cells (MSCs). Collagen nanofibers with diameters of 430 +- 170 nm were fabricated by electrospinning. Over 45% of the MSC population adhered to this collagen nanofiber after 30 min at room temperature. Remarkably, collagen-coated P(LLA-CL) electrospun nanofibers were almost as efficient as collagen nanofibers whereas collagen cast film did not enhance early capture when it was applied on cover slips. The adhesive efficiency could be further increased to over 20% at 20 min and over 55% at 30 min when collagen nanofibers were grafted with monoclonal antibodies recognizing CD29 or CD49a. These data demonstrate that the early adhesive behavior is highly dependent on both the surface texture and the surface chemistry of the substrate. These findings have potential applications for early capture of MSCs in an ex vivo setting under time constraints such as in a surgical setting.

  9. Nanocapillary Adhesion between Parallel Plates.

    Science.gov (United States)

    Cheng, Shengfeng; Robbins, Mark O

    2016-08-01

    Molecular dynamics simulations are used to study capillary adhesion from a nanometer scale liquid bridge between two parallel flat solid surfaces. The capillary force, Fcap, and the meniscus shape of the bridge are computed as the separation between the solid surfaces, h, is varied. Macroscopic theory predicts the meniscus shape and the contribution of liquid/vapor interfacial tension to Fcap quite accurately for separations as small as two or three molecular diameters (1-2 nm). However, the total capillary force differs in sign and magnitude from macroscopic theory for h ≲ 5 nm (8-10 diameters) because of molecular layering that is not included in macroscopic theory. For these small separations, the pressure tensor in the fluid becomes anisotropic. The components in the plane of the surface vary smoothly and are consistent with theory based on the macroscopic surface tension. Capillary adhesion is affected by only the perpendicular component, which has strong oscillations as the molecular layering changes.

  10. Bacterial adhesion and biofilms on surfaces

    Institute of Scientific and Technical Information of China (English)

    Trevor Roger Garrett; Manmohan Bhakoo; Zhibing Zhang

    2008-01-01

    Bacterial adhesion has become a significant problem in industry and in the domicile,and much research has been done for deeper understanding of the processes involved.A generic biological model of bacterial adhesion and population growth called the bacterial biofilm growth cycle,has been described and modified many times.The biofilm growth cycle encompasses bacterial adhesion at all levels,starting with the initial physical attraction of bacteria to a substrate,and ending with the eventual liberation of cell dusters from the biofilm matrix.When describing bacterial adhesion one is simply describing one or more stages of biofilm development,neglecting the fact that the population may not reach maturity.This article provides an overview of bacterial adhesion.cites examples of how bac-terial adhesion affects industry and summarises methods and instrumentation used to improve our understanding of the adhesive prop-erties of bacteria.

  11. Host Selection of Microbiota via Differential Adhesion.

    Science.gov (United States)

    McLoughlin, Kirstie; Schluter, Jonas; Rakoff-Nahoum, Seth; Smith, Adrian L; Foster, Kevin R

    2016-04-13

    The host epithelium is the critical interface with microbial communities, but the mechanisms by which the host regulates these communities are poorly understood. Here we develop the hypothesis that hosts use differential adhesion to select for and against particular members of their microbiota. We use an established computational, individual-based model to study the impact of host factors that regulate adhesion at the epithelial surface. Our simulations predict that host-mediated adhesion can increase the competitive advantage of microbes and create ecological refugia for slow-growing species. We show how positive selection via adhesion can be transformed into negative selection if the host secretes large quantities of a matrix such as mucus. Our work predicts that adhesion is a powerful mechanism for both positive and negative selection within the microbiota. We discuss molecules-mucus glycans and IgA-that affect microbe adhesion and identify testable predictions of the adhesion-as-selection model. PMID:27053168

  12. Adhesive mechanisms in cephalopods: a review.

    Science.gov (United States)

    von Byern, Janek; Klepal, Waltraud

    2006-01-01

    Several genera of cephalopods (Nautilus, Sepia, Euprymna and Idiosepius) produce adhesive secretions, which are used for attachment to the substratum, for mating and to capture prey. These adhesive structures are located in different parts of the body, viz. in the digital tentacles (Nautilus), in the ventral surface of the mantle and fourth arm pair (Sepia), in the dorsal epidermis (Euprymna), or in the dorsal mantle side and partly on the fins (Idiosepius). Adhesion in Sepia is induced by suction of dermal structures on the mantle, while for Nautilus, Euprymna and Idiosepius adhesion is probably achieved by chemical substances. Histochemical studies indicate that in Nautilus and Idiosepius secretory cells that appear to be involved in adhesion stain for carbohydrates and protein, whilst in Euprymna only carbohydrates are detectable. De-adhesion is either achieved by muscle contraction of the tentacles and mantle (Nautilus and Sepia) or by secretion of substances (Euprymna). The de-adhesive mechanism used by Idiosepius remains unknown. PMID:17110356

  13. Syndecans, signaling, and cell adhesion

    DEFF Research Database (Denmark)

    Couchman, J R; Woods, A

    1996-01-01

    Syndecans are transmembrane proteoglycans which can participate in diverse cell surface interactions, involving extracellular matrix macromolecules, growth factors, protease inhibitors, and even viral entry. Currently, all extracellular interactions are believed to be mediated by distinct...... structures within the heparan sulfate chains, leaving the roles of chondroitin sulfate chains and extracellular portion of the core proteins to be elucidated. Evidence that syndecans are a class of receptor involved in cell adhesion is mounting, and their small cytoplasmic domains may link...

  14. Culinary Medicine-Jalebi Adhesions.

    Science.gov (United States)

    Kapoor, Vinay K

    2016-02-01

    Culinary terms have been used to describe anatomy (bean-shaped kidneys), pathology (strawberry gall bladder), clinical signs (café-au-lait spots), radiological images (sausage-shaped pancreas), etc. While Indian cuisine is popular all over the world, no Indian dish finds mention in medical terminology. In intra-abdominal adhesions, sometimes, the intestinal loops are so densely adherent that it is difficult to make out proximal from distal and it is impossible to separate them without injuring the bowel resulting in spill of contents-resection is the only option (Fig. 1). Jalebi, an Indian dessert, has a single long tubular strip of fried batter filled with sugary syrup so intertwined that it is impossible to discern its ends; if broken, the syrup spills out-the best way to relish it is to chew the whole piece (Fig. 2). Because of these similarities between them, I propose to name dense intra-abdominal adhesions as 'jalebi adhesions.' PMID:27186047

  15. Antibody informatics for drug discovery

    DEFF Research Database (Denmark)

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

    2014-01-01

    for antibody rational design using computational approaches to affinity and stability improvement, as well as ab-initio and homology-based antibody modeling; (ii) resources for antibody sequences, structures, and immune epitopes and open drug discovery resources for development of antibody drugs; and (iii...

  16. Block Transfer Handbook: Constructing and Negotiating Block Transfer Agreements.

    Science.gov (United States)

    Finlay, Finola

    The purpose of this handbook is to provide resources for institutions or articulation committees who are engaged in the task of investigating the feasibility of block transfer agreements. Block transfer is the process whereby a block of credits is granted to students who have successfully completed a certificate, diploma, or cluster of courses…

  17. Intercellular adhesion molecule-1 expression by skeletal muscle cells augments myogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Goh, Qingnian; Dearth, Christopher L.; Corbett, Jacob T. [Department of Kinesiology, The University of Toledo, Toledo, OH (United States); Pierre, Philippe [Centre d’Immunologie de Marseille-Luminy U2M, Aix-Marseille Université, Marseille (France); INSERM U631, Institut National de la Santé et Recherche Médicale, Marseille (France); CNRS UMR6102, Centre National de la Recherche Scientifique, Marseille (France); Chadee, Deborah N. [Department of Biological Sciences, The University of Toledo, Toledo, OH (United States); Pizza, Francis X., E-mail: Francis.Pizza@utoledo.edu [Department of Kinesiology, The University of Toledo, Toledo, OH (United States)

    2015-02-15

    We previously demonstrated that the expression of intercellular adhesion molecule-1 (ICAM-1) by skeletal muscle cells after muscle overload contributes to ensuing regenerative and hypertrophic processes in skeletal muscle. The objective of the present study is to reveal mechanisms through which skeletal muscle cell expression of ICAM-1 augments regenerative and hypertrophic processes of myogenesis. This was accomplished by genetically engineering C2C12 myoblasts to stably express ICAM-1, and by inhibiting the adhesive and signaling functions of ICAM-1 through the use of a neutralizing antibody or cell penetrating peptide, respectively. Expression of ICAM-1 by cultured skeletal muscle cells augmented myoblast–myoblast adhesion, myotube formation, myonuclear number, myotube alignment, myotube–myotube fusion, and myotube size without influencing the ability of myoblasts to proliferate or differentiate. ICAM-1 augmented myotube formation, myonuclear accretion, and myotube alignment through a mechanism involving adhesion-induced activation of ICAM-1 signaling, as these dependent measures were reduced via antibody and peptide inhibition of ICAM-1. The adhesive and signaling functions of ICAM-1 also facilitated myotube hypertrophy through a mechanism involving myotube–myotube fusion, protein synthesis, and Akt/p70s6k signaling. Our findings demonstrate that ICAM-1 expression by skeletal muscle cells augments myogenesis, and establish a novel mechanism through which the inflammatory response facilitates growth processes in skeletal muscle. - Highlights: • We examined mechanisms through which skeletal muscle cell expression of ICAM-1 facilitates events of in vitro myogenesis. • Expression of ICAM-1 by cultured myoblasts did not influence their ability to proliferate or differentiate. • Skeletal muscle cell expression of ICAM-1 augmented myoblast fusion, myotube alignment, myotube–myotube fusion, and myotube size. • ICAM-1 augmented myogenic processes through

  18. Engineering antibodies for cancer therapy.

    Science.gov (United States)

    Boder, Eric T; Jiang, Wei

    2011-01-01

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

  19. Inhibition of P-Selectin and PSGL-1 Using Humanized Monoclonal Antibodies Increases the Sensitivity of Multiple Myeloma Cells to Bortezomib.

    Science.gov (United States)

    Muz, Barbara; Azab, Feda; de la Puente, Pilar; Rollins, Scott; Alvarez, Richard; Kawar, Ziad; Azab, Abdel Kareem

    2015-01-01

    Multiple myeloma (MM) is a plasma cell malignancy localized in the bone marrow. Despite the introduction of novel therapies majority of MM patients relapse. We have previously shown that inhibition of P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) play a key role in proliferation of MM and using small-molecule inhibitors of P-selectin/PSGL-1 sensitized MM cells to therapy. However, these small-molecule inhibitors had low specificity to P-selectin and showed poor pharmacokinetics. Therefore, we tested blocking of P-selectin and PSGL-1 using functional monoclonal antibodies in order to sensitize MM cells to therapy. We have demonstrated that inhibiting the interaction between MM cells and endothelial and stromal cells decreased proliferation in MM cells and in parallel induced loose-adhesion to the primary tumor site to facilitate egress. At the same time, blocking this interaction in vivo led to MM cells retention in the circulation and delayed homing to the bone marrow, thus exposing MM cells to bortezomib which contributed to reduced tumor growth and better mice survival. This study provides a better understanding of the biology of P-selectin and PSGL-1 and their roles in dissemination and resensitization of MM to treatment.

  20. Inhibition of P-Selectin and PSGL-1 Using Humanized Monoclonal Antibodies Increases the Sensitivity of Multiple Myeloma Cells to Bortezomib

    Directory of Open Access Journals (Sweden)

    Barbara Muz

    2015-01-01

    Full Text Available Multiple myeloma (MM is a plasma cell malignancy localized in the bone marrow. Despite the introduction of novel therapies majority of MM patients relapse. We have previously shown that inhibition of P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1 play a key role in proliferation of MM and using small-molecule inhibitors of P-selectin/PSGL-1 sensitized MM cells to therapy. However, these small-molecule inhibitors had low specificity to P-selectin and showed poor pharmacokinetics. Therefore, we tested blocking of P-selectin and PSGL-1 using functional monoclonal antibodies in order to sensitize MM cells to therapy. We have demonstrated that inhibiting the interaction between MM cells and endothelial and stromal cells decreased proliferation in MM cells and in parallel induced loose-adhesion to the primary tumor site to facilitate egress. At the same time, blocking this interaction in vivo led to MM cells retention in the circulation and delayed homing to the bone marrow, thus exposing MM cells to bortezomib which contributed to reduced tumor growth and better mice survival. This study provides a better understanding of the biology of P-selectin and PSGL-1 and their roles in dissemination and resensitization of MM to treatment.

  1. Demographic Data - MDC_Block

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — A polygon feature class of Miami-Dade Census 2000 Blocks. Census blocks are areas bounded on all sides by visible and/or invisible features shown on a map prepared...

  2. Effect of methylprednisolone on the oxidative burst activity, adhesion molecules and clinical outcome following open heart surgery

    DEFF Research Database (Denmark)

    Toft, P; Christiansen, K; Tønnesen, Else Kirstine;

    1997-01-01

    Following cardiac surgery with cardiopulmonary bypass (CPB), activated granulocytes may be involved with ischaemia/ reperfusion injury. The purpose of this study was to investigate whether steroids could reduce the oxidative burst activity of granulocytes, the expression of adhesion molecules...... cytometrically using 123-dihydrorhodamine. A panel of adhesion molecules was measured using monoclonal antibodies. Following CPB the oxidative burst activity and the expression of the adhesion molecule L-selectin more than doubled compared to initial values. There was no difference between the steroid group...... and the control group regarding the expression of adhesion molecules or the oxidative burst activity. In the steroid group the fluid gain during extracorporeal circulation (ECC) was 683 ml (median) compared to 1488 ml in the control group. Steroids prevented hyperthermia in the postoperative period but did...

  3. Functional characterization of antibodies against Neisseria gonorrhoeae opacity protein loops.

    Directory of Open Access Journals (Sweden)

    Jessica G Cole

    Full Text Available BACKGROUND: The development of a gonorrhea vaccine is challenged by the lack of correlates of protection. The antigenically variable neisserial opacity (Opa proteins are expressed during infection and have a semivariable (SV and highly conserved (4L loop that could be targeted in a vaccine. Here we compared antibodies to linear (Ab(linear and cyclic (Ab(cyclic peptides that correspond to the SV and 4L loops and selected hypervariable (HV(2 loops for surface-binding and protective activity in vitro and in vivo. METHODS/FINDINGS: Ab(SV cyclic bound a greater number of different Opa variants than Ab(SV linear, including variants that differed by seven amino acids. Antibodies to the 4L peptide did not bind Opa-expressing bacteria. Ab(SV (cyclic and Ab(HV2 (cyclic, but not Ab(SV (linear or Ab(HV2 linear agglutinated homologous Opa variants, and Ab(HV2BD (cyclic but not Ab(HV2BD (linear blocked the association of OpaB variants with human endocervical cells. Only Ab(HV2BD (linear were bactericidal against the serum resistant parent strain. Consistent with host restrictions in the complement cascade, the bactericidal activity of Ab(HV2BD (linear was increased 8-fold when rabbit complement was used. None of the antibodies was protective when administered vaginally to mice. Antibody duration in the vagina was short-lived, however, with <50% of the antibodies recovered 3 hrs post-administration. CONCLUSIONS: We conclude that an SV loop-specific cyclic peptide can be used to induce antibodies that recognize a broad spectrum of antigenically distinct Opa variants and have agglutination abilities. HV(2 loop-specific cyclic peptides elicited antibodies with agglutination and adherence blocking abilities. The use of human complement when testing the bactericidal activity of vaccine-induced antibodies against serum resistant gonococci is also important.

  4. Controversies in the Management of Isolated Congenital Atrioventricular Block.

    Science.gov (United States)

    DeNoble, Anna E; Kuller, Jeffrey A; Rhee, Eleanor J

    2015-08-01

    Congenital atrioventricular block (CAVB) affects approximately 2% of fetuses of mothers with anti-Ro or anti-La antibodies, regardless of maternal rheumatologic symptoms. Anti-Ro and anti-La antibodies are antinuclear antibodies commonly found in autoimmune diseases. Congenital atrioventricular block is associated with a relatively high fetal morbidity and mortality, particularly more advanced degrees of block. There is significant controversy surrounding surveillance of anti-Ro/La-positive pregnancies and treatment of fetuses diagnosed with CAVB. Studies of dexamethasone in the treatment of CAVB have yielded conflicting results, with most suggesting only a limited potential benefit in first- and seconddegree CAVB and in cases complicated by fetal hydrops. Larger prospective studies are needed to further evaluate the efficacy of intravenous immunoglobulin in the treatment of CAVB and of intravenous immunoglobulin and hydroxychloroquine in the prevention of CAVB in fetuses of at-risk mothers. Surveillance and treatment regimens should be determined on a case-by-case basis, taking into consideration the degree of CAVB, costs, and potential adverse effects of treatment.

  5. Porous block nanofiber composite filters

    Energy Technology Data Exchange (ETDEWEB)

    Ginley, David S.; Curtis, Calvin J.; Miedaner, Alexander; Weiss, Alan J.; Paddock, Arnold

    2016-08-09

    Porous block nano-fiber composite (110), a filtration system (10) and methods of using the same are disclosed. An exemplary porous block nano-fiber composite (110) includes a porous block (100) having one or more pores (200). The porous block nano-fiber composite (110) also includes a plurality of inorganic nano-fibers (211) formed within at least one of the pores (200).

  6. Isolation of Human Antibodies Against Hepatitis E From Phage Display Library by Metal Affinity Chromatography

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To isolate human antibodies against hepatitis E virus from phage display library by a new method of panning phage antibody library based on immobilized metal affinity chromatography (IMAC). Methods Phage antibody library was allowed to mix with hex-His tagged expressed HEV specific antigen, NE2, in solution for adequate binding before affinity resin for hex-His was added. The non-specific phage antibodies were removed by extensive washing and the specific bound phage antibodies could then be eluted to infect TG1 or repeat the binding process for subsequent rounds of purification. The specificity of the selected human antibodies were tested by antigen competitive ELISA, human sera blocking ELISA, scFv expression, and sequence analysis. Results His-NE2 specific recombinant phages were successfully enriched after panning procedure. Two individual phage clones, 126 and 138, showed 50% inhibition in NE2 antigen competition ELISA and obvious blocking effect by HEV positive serum in blocking ELISA. Soluble scFv of 126, 138 bound to NE2 specifically. Conclusion Two specific human phage antibodies against hepatitis E virus (HEV) from phage display library were isolated by immobilized metal affinity chromatography. The immobilized metal affinity chromatography applied to phage antibody selection was a helpful supplement to the selection in solution.

  7. A monoclonal antibody toolkit for C. elegans.

    Directory of Open Access Journals (Sweden)

    Gayla Hadwiger

    Full Text Available BACKGROUND: Antibodies are critical tools in many avenues of biological research. Though antibodies can be produced in the research laboratory setting, most research labs working with vertebrates avail themselves of the wide array of commercially available reagents. By contrast, few such reagents are available for work with model organisms. METHODOLOGY/PRINCIPAL FINDINGS: We report the production of monoclonal antibodies directed against a wide range of proteins that label specific subcellular and cellular components, and macromolecular complexes. Antibodies were made to synaptobrevin (SNB-1, a component of synaptic vesicles; to Rim (UNC-10, a protein localized to synaptic active zones; to transforming acidic coiled-coil protein (TAC-1, a component of centrosomes; to CENP-C (HCP-4, which in worms labels the entire length of their holocentric chromosomes; to ORC2 (ORC-2, a subunit of the DNA origin replication complex; to the nucleolar phosphoprotein NOPP140 (DAO-5; to the nuclear envelope protein lamin (LMN-1; to EHD1 (RME-1 a marker for recycling endosomes; to caveolin (CAV-1, a marker for caveolae; to the cytochrome P450 (CYP-33E1, a resident of the endoplasmic reticulum; to beta-1,3-glucuronyltransferase (SQV-8 that labels the Golgi; to a chaperonin (HSP-60 targeted to mitochondria; to LAMP (LMP-1, a resident protein of lysosomes; to the alpha subunit of the 20S subcomplex (PAS-7 of the 26S proteasome; to dynamin (DYN-1 and to the alpha-subunit of the adaptor complex 2 (APA-2 as markers for sites of clathrin-mediated endocytosis; to the MAGUK, protein disks large (DLG-1 and cadherin (HMR-1, both of which label adherens junctions; to a cytoskeletal linker of the ezrin-radixin-moesin family (ERM-1, which localized to apical membranes; to an ERBIN family protein (LET-413 which localizes to the basolateral membrane of epithelial cells and to an adhesion molecule (SAX-7 which localizes to the plasma membrane at cell-cell contacts. In addition to

  8. CORE SATURATION BLOCKING OSCILLATOR

    Science.gov (United States)

    Spinrad, R.J.

    1961-10-17

    A blocking oscillator which relies on core saturation regulation to control the output pulse width is described. In this arrangement an external magnetic loop is provided in which a saturable portion forms the core of a feedback transformer used with the thermionic or semi-conductor active element. A first stationary magnetic loop establishes a level of flux through the saturation portion of the loop. A second adjustable magnet moves the flux level to select a saturation point giving the desired output pulse width. (AEC)

  9. Anti-DNA antibody mediated catalysis is isotype dependent.

    Science.gov (United States)

    Xia, Yumin; Eryilmaz, Ertan; Zhang, Qiuting; Cowburn, David; Putterman, Chaim

    2016-01-01

    Anti-DNA antibodies are the serological hallmark of systemic lupus erythematosus, and participate in the pathogenesis of lupus nephritis by cross-reacting with multiple renal antigens. Previously, using a panel of murine anti-DNA IgGs that share identical variable regions but that differ in the constant regions, we demonstrated that the cross-reaction and renal pathogenicity of anti-DNA antibodies are isotype dependent. In this study, we investigated the catalytic potential of this anti-DNA antibody panel, and determined its isotype dependency. The three isotype switch variants (IgG1, IgG2a, IgG2b) and the parent IgG3 PL9-11 anti-DNA antibodies were compared in their catalysis of 500 base pair linear double stranded DNA and a 12-mer peptide (ALWPPNLHAWVP), by gel analysis, MALDI-TOF mass spectrometry, and nuclear magnetic resonance spectroscopy. The binding affinity of anti-DNA antibodies to double stranded DNA and peptide antigens were assessed by ELISA and surface plasmon resonance. We found that the PL9-11 antibody isotypes vary significantly in their potential to catalyze the cleavage of both linear and double stranded DNA and the proteolysis of peptides. The degree of the cleavage and proteolysis increases with the incubation temperature and time. While different PL9-11 isotypes have the same initial attack sites within the ALWPPNLHAWVP peptide, there was no correlation between binding affinity to the peptide and proteolysis rates. In conclusion, the catalytic properties of anti-DNA antibodies are isotype dependent. This finding provides further evidence that antibodies that share the same variable region, but which have different constant regions, are functionally distinct. The catalytic effects modulated by antibody constant regions need to be considered in the design of therapeutic antibodies (abzymes) and peptides designed to block pathogenic autoantibodies.

  10. Chitosan Adhesive Films for Photochemical Tissue Bonding

    Science.gov (United States)

    Lauto, Antonio; Mawad, Damia; Barton, Matthew; Piller, Sabine C.; Longo, Leonardo

    2011-08-01

    Photochemical tissue bonding (PTB) is a promising sutureless technique for tissue repair. PTB is often achieved by applying a solution of rose bengal (RB) between two tissue edges, which are irradiated by a green laser to crosslink collagen fibers with minimal heat production. In this study, RB has been incorporated in chitosan films to create a novel tissue adhesive that is laser-activated. Materials and Methods. Adhesive films, based on chitosan and containing ˜0.1wt% RB were manufactured and bonded to calf intestine by a solid state laser (wavelength = 532 nm, Fluence ˜110 J/cm2, spot size ˜5 mm). A single-column tensiometer, interfaced with a personal computer, tested the bonding strength. K-type thermocouples recorded the temperature (T) at the adhesive-tissue interface during laser irradiation. Human fibroblasts were also seeded on the adhesive and cultured for 48 hours to assess cell growth. Results and Conclusion. The RB-chitosan adhesive bonded firmly to the intestine (15±2 kPa, n = 31). The adhesion strength dropped to 0.5±0.1 kPa (n = 8) when the laser was not applied to the adhesive. The average temperature of the adhesive increased from 26 °C to 32 °C during laser exposure. Fibroblasts grew confluent on the adhesive without morphological changes. A new biocompatible chitosan adhesive has been developed that bonds photochemically to tissue with minimal temperature increase.

  11. Adhesion enhancement of biomimetic dry adhesives by nanoparticle in situ synthesis

    Science.gov (United States)

    Díaz Téllez, J. P.; Harirchian-Saei, S.; Li, Y.; Menon, C.

    2013-10-01

    A novel method to increase the adhesion strength of a gecko-inspired dry adhesive is presented. Gold nanoparticles are synthesized on the tips of the microfibrils of a polymeric dry adhesive to increase its Hamaker constant. Formation of the gold nanoparticles is qualitatively studied through a colour change in the originally transparent substance and quantitatively analysed using ultraviolet-visible spectrophotometry. A pull-off force test is employed to quantify the adhesion enhancement. Specifically, adhesion forces of samples with and without embedded gold nanoparticles are measured and compared. The experimental results indicate that an adhesion improvement of 135% can be achieved.

  12. Heterogeneity of cell adhesion molecules in the developing nervous system

    Energy Technology Data Exchange (ETDEWEB)

    Williams, R.K.

    1985-01-01

    Cell-surface molecules, especially glycoproteins, are believed to mediate interactions between developing neurons and their environment. These interactions include pathfinding by growing processes, recognition of appropriate targets, and formation of synaptic structures. In order to identify neuronal cell-surface molecules, monoclonal antibodies (Mab's) were prepared against synaptic fractions from adult rat brain. From this group three monoclonal antibodies, designated 3C5.59, 3G5.34, and 3G6.41, that react with cell-surface antigens of embryonic neurons were selected for further study. In immunofluoresence experiments each of these antibodies strongly reacted with the processes of cultured granule cell neurons, the major class of small cerebellar neurons, cultured from developing rat cerebellum. Mab's 3C5.59 and 3G5.34 reacted only with neurons in the cerebellar cultures. Mab 3G6.41, however, also reacted with cultured brain astrocytes. On frozen sections Mab's 3G5.34 and 3G6.41 also strongly stained the molecular layer, the site of active granule cell axon growth, in the developing cerebellum. Monoclonal and polyclonal antibodies specific for the neural cell adhesion molecule (N-CAM) were used to compare the two glycoproteins recognized by Mab 3G6.41 with N-CAM. Band 1, another large neuronal cell-surface glycoprotein was originally identified in mouse N18 neuroblastoma cells. In this study /sup 125/I-labeled N18-derived band 1 was tested for binding to 9 plant lectins and Limulus polyphemus agglutinin coupled to agarose beads. Band 1 solubilized from brain also specifically bound to LCA-agarose, indicating that mannose containing sugar moieties are present on band 1 from brain.

  13. One-Block CYRCA: an automated procedure for identifying multiple-block alignments from single block queries

    OpenAIRE

    Frenkel-Morgenstern, Milana; Singer, Alice; Bronfeld, Hagit; Pietrokovski, Shmuel

    2005-01-01

    One-Block CYRCA is an automated procedure for identifying multiple-block alignments from single block queries (). It is based on the LAMA and CYRCA block-to-block alignment methods. The procedure identifies whether the query blocks can form new multiple-block alignments (block sets) with blocks from a database or join pre-existing database block sets. Using pre-computed LAMA block alignments and CYRCA sets from the Blocks database reduces the computation time. LAMA and CYRCA are highly sensit...

  14. Antibody affinity maturation

    DEFF Research Database (Denmark)

    Skjødt, Mette Louise

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

  15. Functionally Graded Adhesives for Composite Joints

    Science.gov (United States)

    Stapleton, Scott E.; Waas, Anthony M.; Arnold, Steven M.

    2012-01-01

    Adhesives with functionally graded material properties are being considered for use in adhesively bonded joints to reduce the peel stress concentrations located near adherend discontinuities. Several practical concerns impede the actual use of such adhesives. These include increased manufacturing complications, alterations to the grading due to adhesive flow during manufacturing, and whether changing the loading conditions significantly impact the effectiveness of the grading. An analytical study is conducted to address these three concerns. An enhanced joint finite element, which uses an analytical formulation to obtain exact shape functions, is used to model the joint. Furthermore, proof of concept testing is conducted to show the potential advantages of functionally graded adhesives. In this study, grading is achieved by strategically placing glass beads within the adhesive layer at different densities along the joint.

  16. Anti-adhesive properties of fish tropomyosins

    DEFF Research Database (Denmark)

    Vejborg, Rebecca Munk; Bernbom, Nete; Gram, Lone;

    2008-01-01

    Aims: We have recently found that preconditioning of stainless steel surfaces with an aqueous fish muscle extract can significantly impede bacterial adhesion. The purpose of this study was to identify and characterize the primary components associated with this bacteria-repelling effect. Methods...... and Results: The anti-adhesive activity was assayed against Escherchia coli K-12, and bacterial adhesion was quantified by crystal violet staining and sonication methods. Proteolytic digestion, elution and fractionation experiments revealed that the anti-adhesive activity of the extract was linked...... to the formation of a proteinaceous conditioning film composed primarily of fish tropomyosins. These fibrous proteins formed a considerable anti-adhesive conditioning layer on and reduced bacterial adhesion to several different materials including polystyrene, vinyl plastic, stainless steel and glass. The protein...

  17. A batch fabricated biomimetic dry adhesive

    Science.gov (United States)

    Northen, Michael T.; Turner, Kimberly L.

    2005-08-01

    The fine hair adhesive system found in nature is capable of reversibly adhering to just about any surface. This dry adhesive, best demonstrated in the pad of the gecko, makes use of a multilevel conformal structure to greatly increase inelastic surface contact, enhancing short range interactions and producing significant amounts of attractive forces. Recent work has attempted to reproduce and test the terminal submicrometre 'hairs' of the system. Here we report the first batch fabricated multi-scale conformal system to mimic nature's dry adhesive. The approach makes use of massively parallel MEMS processing technology to produce 20-150 µm platforms, supported by single slender pillars, and coated with ~2 µm long, ~200 nm diameter, organic looking polymer nanorods, or 'organorods'. To characterize the structures a new mesoscale nanoindenter adhesion test technique has been developed. Experiments indicate significantly improved adhesion with the multiscale system. Additional processing caused a hydrophilic to hydrophobic transformation of the surface and testing indicated further improvement in adhesion.

  18. The Rheological Property of Potato Starch Adhesives

    Directory of Open Access Journals (Sweden)

    Junjun Liu

    2014-02-01

    Full Text Available The main goal of this study was to use potato starch in the production of environmentally sound adhesives. ‘Three-formaldehyde glue’ pollutes the environment and harms to human health strongly, which widely used for wood-based panels preparation. Environment-friendly potato starch adhesives were prepared using method of oxidation-gelatinization, insteading of the three formaldehyde glue. The effects of the quality ratio of starch and water, temperature and shear rate on the apparent viscosity of the adhesive were studied. The rheological eigenvalue of apparent viscosity was studied through nonlinear regression. The results showed that the apparent viscosity of potato starch adhesives decreased with the increasing of temperature; the apparent viscosity decreased slowly with the increasing of rotor speed; the phenomenon of shear thinning appeared within potato starch adhesives which was pseudo-plastic fluids. Potato starch adhesives with characteristics of non-toxic, no smell and pollution could be applied in interior and upscale packaging.

  19. The wild tapered block bootstrap

    DEFF Research Database (Denmark)

    Hounyo, Ulrich

    In this paper, a new resampling procedure, called the wild tapered block bootstrap, is introduced as a means of calculating standard errors of estimators and constructing confidence regions for parameters based on dependent heterogeneous data. The method consists in tapering each overlapping block...... of the series first, the applying the standard wild bootstrap for independent and heteroscedastic distrbuted observations to overlapping tapered blocks in an appropriate way. Its perserves the favorable bias and mean squared error properties of the tapered block bootstrap, which is the state-of-the-art block......-order asymptotic validity of the tapered block bootstrap as well as the wild tapered block bootstrap approximation to the actual distribution of the sample mean is also established when data are assumed to satisfy a near epoch dependent condition. The consistency of the bootstrap variance estimator for the sample...

  20. Adhesive bowel obstruction? Not always

    Directory of Open Access Journals (Sweden)

    Mittapalli D

    2011-01-01

    Full Text Available A 58-year-old man presented acutely with features of post-surgical adhesive small bowel obstruction. Following an unsuccessful trial of conservative management, computed tomography (CT of the abdomen was performed. This revealed a mass in the ileocaecal region, for which he underwent a subsequent right hemicolectomy. Histology revealed diffuse B-cell Non-Hodgkin′s lymphoma of the terminal ileum. Confounding obstructive lesion of the intestine in patients with a history of previous laparotomy is extremely uncommon. Early high resolution imaging may predict diagnosis and consolidate clinical management plans.

  1. Adhesion molecule expression stimulated by Bacteroides thetaiotaomicron cell-surface antigens.

    Science.gov (United States)

    Rokosz, A; Meisel-Mikołajczyk, F; Malchar, C; Nowaczyk, M; Górski, A

    1999-01-01

    Bacteroides thetaiotaomicron, a Gram-negative anaerobic rod belonging to the Bacteroides fragilis group (BFG), is involved in many systemic and local, most frequently suppurative infections in man. The cell envelope of these rods is composed of two carbohydrate-containing antigens: lipopolysaccharide (LPS) and capsular polysaccharide (CPS). Adhesion molecules ICAM-1, VCAM-1 and E-selectin (ELAM-1) are induced on the endothelial cells by mediators of inflammation. The aim of this study was to assay the ability of B. thetaiotaomicron surface antigens to induce adhesion molecule expression on the endothelial cells. The influence of LPS and CPS on the expression of adhesion molecules on HMEC-1 cell line was examined in an ELISA test. ELISA was performed with monoclonal mouse anti-human: ICAM-1, VCAM-1 and E-selectin antibodies of the IgG class. B. thetaiotaomicron lipopolysaccharides revealed the ability to induce ICAM-1, VCAM-1 and E-selectin expression on the endothelial cells. Their activities were similar, but lower than the activity of Eschericha coli LPS. ICAM-1 was the most stimulated adhesion molecule. The strongest activation by LPS was achieved at the concentrations of 10.0 and 1.0 micrograms/ml. The ability of capsular polysaccharide to induce the expression of adhesion molecules was considerably weaker.

  2. Rolling adhesion of alphaL I domain mutants decorrelated from binding affinity.

    Science.gov (United States)

    Pepper, Lauren R; Hammer, Daniel A; Boder, Eric T

    2006-06-30

    Activated lymphocyte function-associated antigen-1 (LFA-1, alphaLbeta2 integrin) found on leukocytes facilitates firm adhesion to endothelial cell layers by binding to intercellular adhesion molecule-1 (ICAM-1), which is up-regulated on endothelial cells at sites of inflammation. Recent work has shown that LFA-1 in a pre-activation, low-affinity state may also be involved in the initial tethering and rolling phase of the adhesion cascade. The inserted (I) domain of LFA-1 contains the ligand-binding epitope of the molecule, and a conformational change in this region during activation increases ligand affinity. We have displayed wild-type I domain on the surface of yeast and validated expression using I domain specific antibodies and flow cytometry. Surface display of I domain supports yeast rolling on ICAM-1-coated surfaces under shear flow. Expression of a locked open, high-affinity I domain mutant supports firm adhesion of yeast, while yeast displaying intermediate-affinity I domain mutants exhibit a range of rolling phenotypes. We find that rolling behavior for these mutants fails to correlate with ligand binding affinity. These results indicate that unstressed binding affinity is not the only molecular property that determines adhesive behavior under shear flow.

  3. RNA and DNA aptamers as potential tools to prevent cell adhesion in disease

    Directory of Open Access Journals (Sweden)

    Ulrich H.

    2001-01-01

    Full Text Available Recent research has shown that receptor-ligand interactions between surfaces of communicating cells are necessary prerequisites for cell proliferation, cell differentiation and immune defense. Cell-adhesion events have also been proposed for pathological conditions such as cancer growth, metastasis, and host-cell invasion by parasites such as Trypanosoma cruzi. RNA and DNA aptamers (aptus = Latin, fit that have been selected from combinatorial nucleic acid libraries are capable of binding to cell-adhesion receptors leading to a halt in cellular processes induced by outside signals as a consequence of blockage of receptor-ligand interactions. We outline here a novel approach using RNA aptamers that bind to T. cruzi receptors and interrupt host-cell invasion in analogy to existing procedures of blocking selectin adhesion and function in vitro and in vivo.

  4. Antithyroglobulin Antibodies and Antimicrosomal Antibodies in Various Thyroid Diseases

    Energy Technology Data Exchange (ETDEWEB)

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

    1979-03-15

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

  5. Pharmacology of cell adhesion molecules of the nervous system

    DEFF Research Database (Denmark)

    Kiryushko, Darya; Bock, Elisabeth; Berezin, Vladimir

    2007-01-01

    development. The majority of CAMs are signal transducing receptors. CAM-induced intracellular signalling is triggered via homophilic (CAM-CAM) and heterophilic (CAM - other counter-receptors) interactions, which both can be targeted pharmacologically. We here describe the progress in the CAM pharmacology...... focusing on cadherins and CAMs of the immunoglobulin (Ig) superfamily, such as NCAM and L1. Structural basis of CAM-mediated cell adhesion and CAM-induced signalling are outlined. Different pharmacological approaches to study functions of CAMs are presented including the use of specific antibodies......, recombinant proteins, and synthetic peptides. We also discuss how unravelling of the 3D structure of CAMs provides novel pharmacological tools for dissection of CAM-induced signalling pathways and offers therapeutic opportunities for a range of neurological disorders....

  6. Factors influencing bacterial adhesion to contact lenses

    OpenAIRE

    Dutta, Debarun; Cole, Nerida; Willcox, Mark

    2012-01-01

    The process of any contact lens related keratitis generally starts with the adhesion of opportunistic pathogens to contact lens surface. This article focuses on identifying the factors which have been reported to affect bacterial adhesion to contact lenses. Adhesion to lenses differs between various genera/species/strains of bacteria. Pseudomonas aeruginosa, which is the predominant causative organism, adheres in the highest numbers to both hydrogel and silicone hydrogel lenses in vitro. The ...

  7. Syndecan-4 and focal adhesion function

    DEFF Research Database (Denmark)

    Woods, A; Couchman, J R

    2001-01-01

    Two groups have now reported the viability of mice that lack syndecan-4. These mice have wound healing/angiogenesis problems, and fibroblasts from these animals differ in adhesion and migration from normal. This is consistent with recent in vitro data indicating a need for signaling via syndecan-4...... for focal adhesion formation, and reports that overexpression of proteins that bind syndecan-4 can modify cell adhesion and migration....

  8. Ligation of Fc gamma receptor IIB inhibits antibody-dependent enhancement of dengue virus infection.

    Science.gov (United States)

    Chan, Kuan Rong; Zhang, Summer Li-Xin; Tan, Hwee Cheng; Chan, Ying Kai; Chow, Angelia; Lim, Angeline Pei Chiew; Vasudevan, Subhash G; Hanson, Brendon J; Ooi, Eng Eong

    2011-07-26

    The interaction of antibodies, dengue virus (DENV), and monocytes can result in either immunity or enhanced virus infection. These opposing outcomes of dengue antibodies have hampered dengue vaccine development. Recent studies have shown that antibodies neutralize DENV by either preventing virus attachment to cellular receptors or inhibiting viral fusion intracellularly. However, whether the antibody blocks attachment or fusion, the resulting immune complexes are expected to be phagocytosed by Fc gamma receptor (FcγR)-bearing cells and cleared from circulation. This suggests that only antibodies that are able to block fusion intracellularly would be able to neutralize DENV upon FcγR-mediated uptake by monocytes whereas other antibodies would have resulted in enhancement of DENV replication. Using convalescent sera from dengue patients, we observed that neutralization of the homologous serotypes occurred despite FcγR-mediated uptake. However, FcγR-mediated uptake appeared to be inhibited when neutralized heterologous DENV serotypes were used instead. We demonstrate that this inhibition occurred through the formation of viral aggregates by antibodies in a concentration-dependent manner. Aggregation of viruses enabled antibodies to cross-link the inhibitory FcγRIIB, which is expressed at low levels but which inhibits FcγR-mediated phagocytosis and hence prevents antibody-dependent enhancement of DENV infection in monocytes. PMID:21746897

  9. Influence of composition on the adhesive strength and initial viscosity of denture adhesives.

    Science.gov (United States)

    Han, Jian-min; Hong, Guang; Hayashida, Kentaro; Maeda, Takeshi; Murata, Hiroshi; Sasaki, Keiichi

    2014-01-01

    To investigate the effect of composition on the initial viscosity and adhesive strength between denture adhesives and the denture base. Two types of water-soluble polymers (methoxy ethylene maleic anhydride copolymer [PVM-MA] and sodium carboxymethyl cellulose [CMC]) were used. Samples were divided into three groups. Group 1 contained only PVM-MA; Group 2 contained only CMC; and Group 3 contained PVM-MA and CMC. The initial viscosity and adhesive strength were measured. For Group 1, the initial viscosity increased significantly as PVM-MA content increased. The adhesive strength of Group 1 lasted longer than Group 2. The adhesive strength of Group 3 varied greatly. The ratio of CMC and PVM-MA has a significant effect on the initial viscosity and adhesive strength of denture adhesives. Our results suggest that it is possible to improve the durability of a denture adhesive by combining different water-soluble polymers.

  10. Nucleation and growth of cadherin adhesions

    International Nuclear Information System (INIS)

    Cell-cell contact formation relies on the recruitment of cadherin molecules and their anchoring to actin. However, the precise chronology of events from initial cadherin trans-interactions to adhesion strengthening is unclear, in part due to the lack of access to the distribution of cadherins within adhesion zones. Using N-cadherin expressing cells interacting with N-cadherin coated surfaces, we characterized the formation of cadherin adhesions at the ventral cell surface. TIRF and RIC microscopies revealed streak-like accumulations of cadherin along actin fibers. FRAP analysis indicated that engaged cadherins display a slow turnover at equilibrium, compatible with a continuous addition and removal of cadherin molecules within the adhesive contact. Association of cadherin cytoplasmic tail to actin as well as actin cables and myosin II activity are required for the formation and maintenance of cadherin adhesions. Using time lapse microscopy we deciphered how cadherin adhesions form and grow. As lamellipodia protrude, cadherin foci stochastically formed a few microns away from the cell margin. Neo-formed foci coalesced aligned and coalesced with preformed foci either by rearward sliding or gap filling to form cadherin adhesions. Foci experienced collapse at the rear of cadherin adhesions. Based on these results, we present a model for the nucleation, directional growth and shrinkage of cadherin adhesions

  11. Adhesion of rhodium films on metallic substrates

    Energy Technology Data Exchange (ETDEWEB)

    Marot, L. [Department of Physics, University of Basel, Klingelbergstrasse 82, CH-4056 Basel (Switzerland)], E-mail: laurent.marot@unibas.ch; Covarel, G.; Tuilier, M.-H. [Laboratoire Mecanique, Materiaux et Procedes de Fabrication, Pole STIC-SPI-Math 61 rue Albert Camus, Universite de Haute-Alsace, F-68093 - Mulhouse Cedex (France); Steiner, R.; Oelhafen, P. [Department of Physics, University of Basel, Klingelbergstrasse 82, CH-4056 Basel (Switzerland)

    2008-09-01

    Rhodium coated metallic films were prepared by magnetron sputtering on metallic substrates. All films were elaborated in same conditions on copper, molybdenum and stainless steel. Adhesion strength tests were carried out by scratch test. The results reveal that the adhesion strength between the film and the substrate is influenced by the hardness of the substrate. Increase of deposition temperature improves the adhesion of the coating. In addition, pre-treatment of substrates by a filtered cathodic vacuum arc and the layer thickness have has some effects on the final adhesion strength.

  12. A monoclonal antibody to triplex DNA binds to eucaryotic chromosomes.

    OpenAIRE

    Lee, J. S.; Burkholder, G D; Latimer, L J; Haug, B L; Braun, R P

    1987-01-01

    A monoclonal antibody (Jel 318) was produced by immunizing mice with poly[d(TmC)].poly[d(GA)].poly[d(mCT) which forms a stable triplex at neutral pH. Jel 318 did not bind to calf thymus DNA or other non pyrimidine.purine DNAs such as poly[d(TG)].poly[d(CA)]. In addition the antibody did not recognize pyrimidine.purine DNAs containing mA (e.g. poly[d(TC)].poly[d(GmA)]) which cannot form a triplex since the methyl group blocks Hoogsteen base-pairing. The binding of Jel 318 to chromosomes was as...

  13. Adhesive proteins of stalked and acorn barnacles display homology with low sequence similarities.

    Directory of Open Access Journals (Sweden)

    Jaimie-Leigh Jonker

    Full Text Available Barnacle adhesion underwater is an important phenomenon to understand for the prevention of biofouling and potential biotechnological innovations, yet so far, identifying what makes barnacle glue proteins 'sticky' has proved elusive. Examination of a broad range of species within the barnacles may be instructive to identify conserved adhesive domains. We add to extensive information from the acorn barnacles (order Sessilia by providing the first protein analysis of a stalked barnacle adhesive, Lepas anatifera (order Lepadiformes. It was possible to separate the L. anatifera adhesive into at least 10 protein bands using SDS-PAGE. Intense bands were present at approximately 30, 70, 90 and 110 kilodaltons (kDa. Mass spectrometry for protein identification was followed by de novo sequencing which detected 52 peptides of 7-16 amino acids in length. None of the peptides matched published or unpublished transcriptome sequences, but some amino acid sequence similarity was apparent between L. anatifera and closely-related Dosima fascicularis. Antibodies against two acorn barnacle proteins (ab-cp-52k and ab-cp-68k showed cross-reactivity in the adhesive glands of L. anatifera. We also analysed the similarity of adhesive proteins across several barnacle taxa, including Pollicipes pollicipes (a stalked barnacle in the order Scalpelliformes. Sequence alignment of published expressed sequence tags clearly indicated that P. pollicipes possesses homologues for the 19 kDa and 100 kDa proteins in acorn barnacles. Homology aside, sequence similarity in amino acid and gene sequences tended to decline as taxonomic distance increased, with minimum similarities of 18-26%, depending on the gene. The results indicate that some adhesive proteins (e.g. 100 kDa are more conserved within barnacles than others (20 kDa.

  14. Block Voter Model

    CERN Document Server

    Sampaio, C I N

    2011-01-01

    We introduce and study the block voter model with noise on two-dimensional square lattices using Monte Carlo simulations and finite-size scaling techniques. The model is defined by an outflow dynamics where a central set of $N_{PCS}$ spins, here denoted by persuasive cluster spins (PCS), tries to influence the opinion of their neighbouring counterparts. We consider the collective behaviour of the entire system with varying PCS size. When $N_{PCS}>2$, the system exhibits an order-disorder phase transition at a critical noise parameter $q_{c}$ which is a monotonically increasing function of the size of the persuasive cluster. We conclude that how large the PCS is more power of persuasion it has. It also seems that the resulting critical behaviour is Ising-like independent of the range of the interactions.

  15. Spintronics: Conceptual Building Blocks

    Science.gov (United States)

    Ansermet, J.-Ph.

    The purpose of this introduction to spintronics is to provide some elementary description of its conceptual building blocks. Thus, it is intended for a newcomer to the field. After recalling rudimentary descriptions of spin precession and spin relaxation, spin-dependent transport is treated within the Boltzmann formalism. This suffices to introduce key notions such as the spin asymmetry of the conductivities in the two-current model, the spin diffusion length, and spin accumulation. Two basic mechanisms of spin relaxation are then presented, one arising from spin-orbit scattering and the other from electron-magnon collisions. Finally, the action of a spin-polarized current on magnetization is presented in a thermodynamics framework. This introduces the notion of spin torque and the characteristic length scale over which the transverse spin polarization of conduction electron decays as it is injected into a magnet.

  16. Photovoltaic building blocks

    DEFF Research Database (Denmark)

    Hanberg, Peter Jesper; Jørgensen, Anders Michael

    2014-01-01

    it directcompetitive with fossil energy sources a further reduction is needed. By increasing the efficiency of the solar cells one gain an advantage through the whole chain of cost. So that per produced Watt of power less material is spent, installation costs are lower, less area is used etc. With an average...... efficiency of about 15% for commercial Silicon solar cells there is still much to gain. DTU Danchip provides research facilities, equipment and expertise for the building blocks that comprises fabricating the efficient solar cell. In order to get more of the sun light into the device we provide thin film......Photovoltaics (PV), better known as solar cells, are now a common day sight on many rooftops in Denmark.The installed capacity of PV systems worldwide is growing exponentially1 and is the third most importantrenewable energy source today. The cost of PV is decreasing fast with ~10%/year but to make...

  17. Atomic Basic Blocks

    Science.gov (United States)

    Scheler, Fabian; Mitzlaff, Martin; Schröder-Preikschat, Wolfgang

    Die Entscheidung, einen zeit- bzw. ereignisgesteuerten Ansatz für ein Echtzeitsystem zu verwenden, ist schwierig und sehr weitreichend. Weitreichend vor allem deshalb, weil diese beiden Ansätze mit äußerst unterschiedlichen Kontrollflussabstraktionen verknüpft sind, die eine spätere Migration zum anderen Paradigma sehr schwer oder gar unmöglich machen. Wir schlagen daher die Verwendung einer Zwischendarstellung vor, die unabhängig von der jeweils verwendeten Kontrollflussabstraktion ist. Für diesen Zweck verwenden wir auf Basisblöcken basierende Atomic Basic Blocks (ABB) und bauen darauf ein Werkzeug, den Real-Time Systems Compiler (RTSC) auf, der die Migration zwischen zeit- und ereignisgesteuerten Systemen unterstützt.

  18. A comparison of a solid phase IRC assay and the PSIFT for detection of antibodies to platelets.

    Science.gov (United States)

    Häcker-Shahin, B; Giannitsis, D J

    1992-01-01

    A rapid solid phase indicator red cells assay (IRCA) for detection of platelet antibodies was developed and its sensitivity compared with PSIFT. Platelets were attached to the surface of polystyrene microtitre plate wells by means of a sodium carbonate buffer and centrifugation. Uncovered areas were blocked by a gelatin blocking buffer. After serum incubation bound platelet-specific antibodies were made visible by anti-IgG-coated indicator red cells and a brief centrifugation. A positive result, meaning the presence of an anti-platelet antibody was indicated by red cell adherence over the reaction surface. In the absence of serum antibodies to platelets the indicator red cells formed a pellet. The IRCA showed a high sensitivity; the anti-platelet antibody Thrombocyte was detectable until a dilution of 1:1,600 whereas the same antibody in the PSIFT could only be detected until a dilution of 1:400.

  19. The Block-block Bootstrap: Improved Asymptotic Refinements

    OpenAIRE

    Donald W.K. Andrews

    2002-01-01

    The asymptotic refinements attributable to the block bootstrap for time series are not as large as those of the nonparametric iid bootstrap or the parametric bootstrap. One reason is that the independence between the blocks in the block bootstrap sample does not mimic the dependence structure of the original sample. This is the join-point problem. In this paper, we propose a method of solving this problem. The idea is not to alter the block bootstrap. Instead, we alter the original sample sta...

  20. Convergence rates of empirical block length selectors for block bootstrap

    OpenAIRE

    Nordman, Daniel J.; Lahiri, Soumendra N.

    2014-01-01

    We investigate the accuracy of two general non-parametric methods for estimating optimal block lengths for block bootstraps with time series – the first proposed in the seminal paper of Hall, Horowitz and Jing (Biometrika 82 (1995) 561–574) and the second from Lahiri et al. (Stat. Methodol. 4 (2007) 292–321). The relative performances of these general methods have been unknown and, to provide a comparison, we focus on rates of convergence for these block length selectors for the moving block ...

  1. Monoclonal antibodies in myeloma

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  2. Prediction of Antibody Epitopes

    DEFF Research Database (Denmark)

    Nielsen, Morten; Marcatili, Paolo

    2015-01-01

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

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

    DEFF Research Database (Denmark)

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

    1997-01-01

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

  4. Design and fabrication of polymer based dry adhesives inspired by the gecko adhesive system

    Science.gov (United States)

    Jin, Kejia

    There has been significant interest in developing dry adhesives mimicking the gecko adhesive system, which offers several advantages compared to conventional pressure sensitive adhesives. Specifically, gecko adhesive pads have anisotropic adhesion properties: the adhesive pads (spatulae) stick strongly when sheared in one direction but are non-adherent when sheared in the opposite direction. This anisotropy property is attributed to the complex topography of the array of fine tilted and curved columnar structures (setae) that bear the spatulae. In this thesis, easy, scalable methods, relying on conventional and unconventional techniques are presented to incorporate tilt in the fabrication of synthetic polymer-based dry adhesives mimicking the gecko adhesive system, which provide anisotropic adhesion properties. In the first part of the study, the anisotropic adhesion and friction properties of samples with various tilt angles to test the validity of a nanoscale tape-peeling model of spatular function are measured. Consistent with the Peel Zone model, samples with lower tilt angles yielded larger adhesion forces. Contact mechanics of the synthetic array were highly anisotropic, consistent with the frictional adhesion model and gecko-like. Based on the original design, a new design of gecko-like dry adhesives was developed which showed superior tribological properties and furthermore showed anisotropic adhesive properties without the need for tilt in the structures. These adhesives can be used to reversibly suspend weights from vertical surfaces (e.g., walls) and, for the first time to our knowledge, horizontal surfaces (e.g., ceilings) by simultaneously and judiciously activating anisotropic friction and adhesion forces. Furthermore, adhesion properties between artificial gecko-inspired dry adhesives and rough substrates with varying roughness are studied. The results suggest that both adhesion and friction forces on a rough substrate depends significantly on the

  5. Large Block Test Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Lin, W

    2001-12-01

    This report documents the Large-Block Test (LBT) conducted at Fran Ridge near Yucca Mountain, Nevada. The LBT was a thermal test conducted on an exposed block of middle non-lithophysal Topopah Spring tuff (Tptpmn) and was designed to assist in understanding the thermal-hydrological-mechanical-chemical (THMC) processes associated with heating and then cooling a partially saturated fractured rock mass. The LBT was unique in that it was a large (3 x 3 x 4.5 m) block with top and sides exposed. Because the block was exposed at the surface, boundary conditions on five of the six sides of the block were relatively well known and controlled, making this test both easier to model and easier to monitor. This report presents a detailed description of the test as well as analyses of the data and conclusions drawn from the test. The rock block that was tested during the LBT was exposed by excavation and removal of the surrounding rock. The block was characterized and instrumented, and the sides were sealed and insulated to inhibit moisture and heat loss. Temperature on the top of the block was also controlled. The block was heated for 13 months, during which time temperature, moisture distribution, and deformation were monitored. After the test was completed and the block cooled down, a series of boreholes were drilled, and one of the heater holes was over-cored to collect samples for post-test characterization of mineralogy and mechanical properties. Section 2 provides background on the test. Section 3 lists the test objectives and describes the block site, the site configuration, and measurements made during the test. Section 3 also presents a chronology of events associated with the LBT, characterization of the block, and the pre-heat analyses of the test. Section 4 describes the fracture network contained in the block. Section 5 describes the heating/cooling system used to control the temperature in the block and presents the thermal history of the block during the test

  6. Lupus anticoagulants and antiphospholipid antibodies

    Science.gov (United States)

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

  7. Cell adhesion molecules involved in the leukocyte recruitment induced by venom of the snake Bothrops jararaca

    Directory of Open Access Journals (Sweden)

    Stella R. Zamuner

    2002-01-01

    Full Text Available It has been shown that Bothrops jararaca venom (BjV induces a significant leukocyte accumulation, mainly neutrophils, at the local of tissue damage. Therefore, the role of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1, LECAM-1, CD18, leukocyte function-associated antigen-1 (LFA-1 and platelet endothelial cell adhesion molecule-1 (PECAM-1 on the BjV-induced neutrophil accumulation and the correlation with release of LTB4, TXA2, tumor necrosis factor-α, interleukin (IL-1 and IL-6 have been investigated. Anti-mouse LECAM-1, LFA-1, ICAM-1 and PECAM-1 monoclonal antibody injection resulted in a reduction of 42%, 80%, 66% and 67%, respectively, of neutrophil accumulation induced by BjV (250 μg/kg, intraperitoneal injection in male mice compared with isotype-matched control injected animals. The anti-mouse CD18 monoclonal antibody had no significant effect on venom-induced neutrophil accumulation. Concentrations of LTB4, TXA2, IL-6 and TNF-α were significant increased in the peritoneal exudates of animals injected with venom, whereas no increment in IL-1 was detected. This results suggest that ICAM-1, LECAM-1, LFA-1 and PECAM-1, but not CD18, adhesion molecules are involved in the recruitment of neutrophils into the inflammatory site induced by BjV. This is the first in vivo evidence that snake venom is able to up-regulate the expression of adhesion molecules by both leukocytes and endothelial cells. This venom effect may be indirect, probably through the release of the inflammatory mediators evidenced in the present study.

  8. Crosslinking of the T cell-specific accessory molecules CD7 and CD28 modulates T cell adhesion

    OpenAIRE

    1992-01-01

    Regulated adhesion enables T cells to migrate through tissue and transiently interact with an endless succession of cells. Monoclonal antibody (mAb) engagement of the CD3/T cell receptor (TCR) complex results in a rapid and transient augmentation of the adhesion function of LFA-1 and VLA integrin molecules on human T cells. We show in this study that mAb crosslinking of the T cell-specific accessory molecules CD7 and CD28, or treatment with the Ca2+ ionophore A23187, results in the rapid indu...

  9. Matrix stiffness exerts biphasic control over monocyte-endothelial adhesion via Rho-mediated ICAM-1 clustering.

    Science.gov (United States)

    Scott, Harry A; Quach, Boi; Yang, Xiao; Ardekani, Soroush; Cabrera, Andrea P; Wilson, Randall; Messaoudi-Powers, Ilhem; Ghosh, Kaustabh

    2016-08-01

    Leukocyte-endothelial adhesion is a critical early step in chronic vascular inflammation associated with diabetes, emphysema, and aging. Importantly, these conditions are also marked by abnormal subendothelial matrix crosslinking (stiffness). Yet, whether and how abnormal matrix stiffness contributes to leukocyte-endothelial adhesion remains poorly understood. Using a co-culture of human monocytic cells and human microvascular endothelial cells (ECs) grown on matrices of tunable stiffness, we demonstrate that matrix stiffness exerts biphasic control over monocyte-EC adhesion, with both matrix softening and stiffening eliciting a two-fold increase in this adhesive interaction. This preferential endothelial adhesivity on softer and stiffer matrices was consistent with a significant increase in α-actinin-4-associated endothelial ICAM-1 clustering, a key determinant of monocyte-EC adhesion. Further, the enhanced ICAM-1 clustering on soft and stiff matrices correlated strongly with an increase in Rho activity and ROCK2 expression. Importantly, inhibition of Rho/ROCK activity blocked the effects of abnormal matrix stiffness on ICAM-1 clustering and monocyte-EC adhesion. Thus, these findings implicate matrix stiffness-dependent ICAM-1 clustering as an important regulator of vascular inflammation and provide the rationale for closely examining mechanotransduction pathways as new molecular targets for anti-inflammatory therapy.

  10. Covariant Approaches to Superconformal Blocks

    CERN Document Server

    Fitzpatrick, A Liam; Khandker, Zuhair U; Li, Daliang; Poland, David; Simmons-Duffin, David

    2014-01-01

    We develop techniques for computing superconformal blocks in 4d superconformal field theories. First we study the super-Casimir differential equation, deriving simple new expressions for superconformal blocks for 4-point functions containing chiral operators in theories with N-extended supersymmetry. We also reproduce these results by extending the "shadow formalism" of Ferrara, Gatto, Grillo, and Parisi to supersymmetric theories, where superconformal blocks can be represented as superspace integrals of three-point functions multiplied by shadow three-point functions.

  11. Dimensional Reduction for Conformal Blocks

    CERN Document Server

    Hogervorst, Matthijs

    2016-01-01

    We consider the dimensional reduction of a CFT, breaking multiplets of the d-dimensional conformal group SO(d+1,1) up into multiplets of SO(d,1). This leads to an expansion of d-dimensional conformal blocks in terms of blocks in d-1 dimensions. In particular, we obtain a formula for 3d conformal blocks as an infinite sum over 2F1 hypergeometric functions with closed-form coefficients.

  12. Apigenin inhibits HGF-promoted invasive growth and metastasis involving blocking PI3K/Akt pathway and β4 integrin function in MDA-MB-231 breast cancer cells

    International Nuclear Information System (INIS)

    Hepatocyte growth factor (HGF) and its receptor, Met, known to control invasive growth program have recently been shown to play crucial roles in the survival of breast cancer patients. The diet-derived flavonoids have been reported to possess anti-invasion properties; however, knowledge on the pharmacological and molecular mechanisms in suppressing HGF/Met-mediated tumor invasion and metastasis is poorly understood. In our preliminary study, we use HGF as an invasive inducer to investigate the effect of flavonoids including apigenin, naringenin, genistein and kaempferol on HGF-dependent invasive growth of MDA-MB-231 human breast cancer cells. Results show that apigenin presents the most potent anti-migration and anti-invasion properties by Boyden chamber assay. Furthermore, apigenin represses the HGF-induced cell motility and scattering and inhibits the HGF-promoted cell migration and invasion in a dose-dependent manner. The effect of apigenin on HGF-induced signaling activation involving invasive growth was evaluated by immunoblotting analysis, it shows that apigenin blocks the HGF-induced Akt phosphorylation but not Met, ERK, and JNK phosphorylation. In addition to MDA-MB-231 cells, apigenin exhibits inhibitory effect on HGF-induced Akt phosphorylation in hepatoma SK-Hep1 cells and lung carcinoma A549 cells. By indirect immunofluorescence microscopy assay, apigenin inhibits the HGF-induced clustering of β4 integrin at actin-rich adhesive site and lamellipodia through PI3K-dependent manner. Treatment of apigenin inhibited HGF-stimulated integrin β4 function including cell-matrix adhesion and cell-endothelial cells adhesion in MDA-MB-231 cells. By Akt-siRNA transfection analysis, it confirmed that apigenin inhibited HGF-promoted invasive growth involving blocking PI3K/Akt pathway. Finally, we evaluated the effect of apigenin on HGF-promoted metastasis by lung colonization of tumor cells in nude mice and organ metastasis of tumor cells in chick embryo. By

  13. Recombinant antibodies and tumor targeting

    OpenAIRE

    Sheikholvaezin, Ali

    2006-01-01

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

  14. Immobilized surfactant-nanotube complexes support selectin-mediated capture of viable circulating tumor cells in the absence of capture antibodies.

    Science.gov (United States)

    Mitchell, Michael J; Castellanos, Carlos A; King, Michael R

    2015-10-01

    The metastatic spread of tumor cells from the primary site to anatomically distant organs leads to a poor patient prognosis. Increasing evidence has linked adhesive interactions between circulating tumor cells (CTCs) and endothelial cells to metastatic dissemination. Microscale biomimetic flow devices hold promise as a diagnostic tool to isolate CTCs and develop metastatic therapies, utilizing E-selectin (ES) to trigger the initial rolling adhesion of tumor cells under flow. To trigger firm adhesion and capture under flow, such devices also typically require antibodies against biomarkers thought to be expressed on CTCs. This approach is challenged by the fact that CTCs are now known to exhibit heterogeneous expression of conventional biomarkers. Here, we describe surfactant-nanotube complexes to enhance ES-mediated capture and isolation of tumor cells without the use of capture antibodies. While the majority of tumor cells exhibited weaker rolling adhesion on halloysite nanotubes (HNT) coated with ES, HNT functionalization with the sodium dodecanoate (NaL) surfactant induced a switch to firm cellular adhesion under flow. Conversely, surfactant-nanotube complexes significantly reduced the number of primary human leukocytes captured via ES-mediated adhesion under flow. The switch in tumor cell adhesion was exploited to capture and isolate tumor cells in the absence of EpCAM antibodies, commonly utilized as the gold standard for CTC isolation. Additionally, HNT-NaL complexes were shown to capture tumor cells with low to negligible EpCAM expression, that are not efficiently captured using conventional approaches.

  15. Intercellular adhesion molecule-1 clusters during osteoclastogenesis

    NARCIS (Netherlands)

    V. Bloemen; T.J. de Vries; T. Schoenmaker; V. Everts

    2009-01-01

    Adhesion between osteoblasts and osteoclast precursors is established via an interaction involving intercellular adhesion molecule-1 (ICAM-1) on osteoblasts and leukocyte function-associated antigen-1 (LFA-1) on osteoclast precursors. The latter cells also express ICAM-1, but little is known about t

  16. Tuneable adhesion through novel binder technologies

    NARCIS (Netherlands)

    Wouters, M.E.L.; Burghoorn, M.M.A.; Ingenhut, B.; Timmer, K.; Rentrop, C.H.A.; Bots, T.L.; Oosterhuis, G.; Fischer, H.R.

    2011-01-01

    A reversible crosslinking mechanism enabling bonding and debonding of adhesives and coatings based on Diels-Alder chemistry is described. The Diels-Alder compounds form a covalently crosslinked network at low temperatures that break at elevated temperatures. As a result, the adhesive exhibits good s

  17. Synthesis of melamine-glucose resin adhesive

    Institute of Scientific and Technical Information of China (English)

    CHEN; Shuanhu; ZHANG; Lei

    2005-01-01

    The synthesis of a novel melamine-glucose adhesive that is similar to urea-formaldehyde adhesive is reported in this paper. The conditions of synthesis, such as the initial pH, the quantity of catalyst, the temperature of reaction, the percentage of each reactant and the time of reaction, were optimized by using the orthogonal experimental method.

  18. Consequences and complications of peritoneal adhesions

    NARCIS (Netherlands)

    Goor, H. van

    2007-01-01

    Consequences and complications of postsurgical intra-abdominal adhesion formation not including small bowel obstruction and secondary infertility are substantial but are under-exposed in the literature. Inadvertent enterotomy during reopening of the abdomen or subsequent adhesion dissection is a fea

  19. Pathophysiology and prevention of postoperative peritoneal adhesions

    Institute of Scientific and Technical Information of China (English)

    Willy Arung1; Michel Meurisse; Olivier Detry

    2011-01-01

    Peritoneal adhesions represent an important clinical challenge in gastrointestinal surgery. Peritoneal adhesions are a consequence of peritoneal irritation by infection or surgical trauma, and may be considered as the pathological part of healing following any peritoneal injury, particularly due to abdominal surgery. The balance between fibrin deposition and degradation is critical in determining normal peritoneal healing or adhesion formation. Postoperative peritoneal adhesions are a major cause of morbidity resulting in multiple complications, many of which may manifest several years after the initial surgical procedure. In addition to acute small bowel obstruction, peritoneal adhesions may cause pelvic or abdominal pain, and infertility. In this paper, the authors reviewed the epidemiology, pathogenesis and various prevention strategies of adhesion formation, using Medline and PubMed search. Several preventive agents against postoperative peritoneal adhesions have been investigated. Their role aims in activating fibrinolysis, hampering coagulation, diminishing the inflammatory response, inhibiting collagen synthesis or creating a barrier between adjacent wound surfaces. Their results are encouraging but most of them are contradictory and achieved mostly in animal model. Until additional findings from future clinical researches, only a meticulous surgery can be recommended to reduce unnecessary morbidity and mortality rates from these untoward effects of surgery. In the current state of knowledge, pre-clinical or clinical studies are still necessary to evaluate the effectiveness of the several proposed prevention strategies of postoperative peritoneal adhesions.

  20. Syndecans: synergistic activators of cell adhesion

    DEFF Research Database (Denmark)

    Woods, A; Couchman, J R

    1998-01-01

    Cell-surface proteoglycans participate in cell adhesion, growth-factor signalling, lipase activity and anticoagulation. Until recently, only the roles of the glycosaminoglycan chains were investigated. Now, with molecular characterization of several core proteins, the roles of each individual...... molecules modulating integrin-based adhesion....

  1. Adhesive loose packings of small dry particles

    Science.gov (United States)

    Liu, Wenwei; Li, Shuiqing; Baule, Adrian; Makse, Hernán A.

    We explore adhesive loose packings of dry small spherical particles of micrometer size using 3D discrete-element simulations with adhesive contact mechanics. A dimensionless adhesion parameter ($Ad$) successfully combines the effects of particle velocities, sizes and the work of adhesion, identifying a universal regime of adhesive packings for $Ad>1$. The structural properties of the packings in this regime are well described by an ensemble approach based on a coarse-grained volume function that includes correlations between bulk and contact spheres. Our theoretical and numerical results predict: (i) An equation of state for adhesive loose packings that appears as a continuation from the frictionless random close packing (RCP) point in the jamming phase diagram; (ii) The existence of a maximal loose packing point at the coordination number $Z=2$ and packing fraction $\\phi=1/2^{3}$. Our results highlight that adhesion leads to a universal packing regime at packing fractions much smaller than the random loose packing, which can be described within a statistical mechanical framework. We present a general phase diagram of jammed matter comprising frictionless, frictional, adhesive as well as non-spherical particles, providing a classification of packings in terms of their continuation from the spherical frictionless RCP.

  2. Switchable adhesion by chemical functionality and topography

    NARCIS (Netherlands)

    Kamperman, M.M.G.; Synytska, A.

    2012-01-01

    Progress in adhesion technology over the last few decades has led to widespread replacement of mechanical fasteners with adhesive bonds. Despite the advances, it remains challenging to produce materials that are sticky on demand. In this feature article we highlight recent efforts to develop reversi

  3. Image analysis of blood platelets adhesion.

    Science.gov (United States)

    Krízová, P; Rysavá, J; Vanícková, M; Cieslar, P; Dyr, J E

    2003-01-01

    Adhesion of blood platelets is one of the major events in haemostatic and thrombotic processes. We studied adhesion of blood platelets on fibrinogen and fibrin dimer sorbed on solid support material (glass, polystyrene). Adhesion was carried on under static and dynamic conditions and measured as percentage of the surface covered with platelets. Within a range of platelet counts in normal and in thrombocytopenic blood we observed a very significant decrease in platelet adhesion on fibrin dimer with bounded active thrombin with decreasing platelet count. Our results show the imperative use of platelet poor blood preparations as control samples in experiments with thrombocytopenic blood. Experiments carried on adhesive surfaces sorbed on polystyrene showed lower relative inaccuracy than on glass. Markedly different behaviour of platelets adhered on the same adhesive surface, which differed only in support material (glass or polystyrene) suggest that adhesion and mainly spreading of platelets depends on physical quality of the surface. While on polystyrene there were no significant differences between fibrin dimer and fibrinogen, adhesion measured on glass support material markedly differed between fibrin dimer and fibrinogen. We compared two methods of thresholding in image analysis of adhered platelets. Results obtained by image analysis of spreaded platelets showed higher relative inaccuracy than results obtained by image analysis of platelets centres and aggregates.

  4. Shear adhesion strength of aligned electrospun nanofibers.

    Science.gov (United States)

    Najem, Johnny F; Wong, Shing-Chung; Ji, Guang

    2014-09-01

    Inspiration from nature such as insects' foot hairs motivates scientists to fabricate nanoscale cylindrical solids that allow tens of millions of contact points per unit area with material substrates. In this paper, we present a simple yet robust method for fabricating directionally sensitive shear adhesive laminates. By using aligned electrospun nylon-6, we create dry adhesives, as a succession of our previous work on measuring adhesion energies between two single free-standing electrospun polymer fibers in cross-cylinder geometry, randomly oriented membranes and substrate, and peel forces between aligned fibers and substrate. The synthetic aligned cylindrical solids in this study are electrically insulating and show a maximal Mode II shear adhesion strength of 27 N/cm(2) on a glass slide. This measured value, for the purpose of comparison, is 270% of that reported from gecko feet. The Mode II shear adhesion strength, based on a commonly known "dead-weight" test, is 97-fold greater than the Mode I (normal) adhesion strength of the same. The data indicate a strong shear binding on and easy normal lifting off. Anisotropic adhesion (Mode II/Mode I) is pronounced. The size and surface boundary effects, crystallinity, and bending stiffness of fibers are used to understand these electrospun nanofibers, which vastly differ from otherwise known adhesive technologies. The anisotropic strength distribution is attributed to a decreasing fiber diameter and an optimized laminate thickness, which, in turn, influences the bending stiffness and solid-state "wettability" of points of contact between nanofibers and surface asperities.

  5. Mechanisms of temporary adhesion in benthic animals

    NARCIS (Netherlands)

    Dodou, D.; Breedveld, P.; Winter, J.C.F.; Dankelman, J.; Leeuwen, van J.L.

    2011-01-01

    Adhesive systems are ubiquitous in benthic animals and play a key role in diverse functions such as locomotion, food capture, mating, burrow building, and defence. For benthic animals that release adhesives, surface and material properties and external morphology have received little attention compa

  6. Evaluation of progestogens for postoperative adhesion prevention.

    Science.gov (United States)

    Beauchamp, P J; Quigley, M M; Held, B

    1984-10-01

    Progesterone (P) has been shown to have potent antiinflammatory and immunosuppressive properties. Previous reports have suggested that the use of P decreases postoperative adhesion formation. To further evaluate the role of pharmacologic doses of progestogens in adhesion prevention, 42 mature New Zealand White rabbits underwent standardized injuries to the uterine horns, fimbriae, and pelvic peritoneum and received one of six treatments. Group S had intraperitoneal placement of normal saline (0.9%); group H received intraperitoneal placement of 32% dextran 70; group IM-P received intramuscular P-in-oil 10 days before and after laparotomy in addition to intraperitoneal saline; group IP-P had intraperitoneal placement of an aqueous P suspension; group DP received medroxyprogesterone acetate intraperitoneally; and group C received no intramuscular or intraperitoneal adhesion-prevention agents. The animals were sacrificed 6 weeks after laparotomy, and the adhesions were scored. Intraperitoneal saline (group S) significantly reduced the amount of adhesions when compared with the control group (C) (P less than 0.05). No significant difference was observed when group S was compared with group H. Intramuscular P added to saline (group IM-P) did not cause further reduction in adhesions when compared with group S. Both group IP-P and group DP had more adhesions than did group S (P less than 0.01). These data fail to support previous claims regarding adhesion prevention by the use of locally or parenterally administered progestogens. PMID:6237937

  7. Antibody Recognition of a Highly Conserved Influenza Virus Epitope

    Energy Technology Data Exchange (ETDEWEB)

    Ekiert, Damian C.; Bhabha, Gira; Elsliger, Marc-André; Friesen, Robert H.E.; Jongeneelen, Mandy; Throsby, Mark; Goudsmit, Jaap; Wilson, Ian A.; Scripps; Crucell

    2009-05-21

    Influenza virus presents an important and persistent threat to public health worldwide, and current vaccines provide immunity to viral isolates similar to the vaccine strain. High-affinity antibodies against a conserved epitope could provide immunity to the diverse influenza subtypes and protection against future pandemic viruses. Cocrystal structures were determined at 2.2 and 2.7 angstrom resolutions for broadly neutralizing human antibody CR6261 Fab in complexes with the major surface antigen (hemagglutinin, HA) from viruses responsible for the 1918 H1N1 influenza pandemic and a recent lethal case of H5N1 avian influenza. In contrast to other structurally characterized influenza antibodies, CR6261 recognizes a highly conserved helical region in the membrane-proximal stem of HA1 and HA2. The antibody neutralizes the virus by blocking conformational rearrangements associated with membrane fusion. The CR6261 epitope identified here should accelerate the design and implementation of improved vaccines that can elicit CR6261-like antibodies, as well as antibody-based therapies for the treatment of influenza.

  8. Role of cell adhesion signal molecules in hepatocellular carcinoma cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    Jian-Min Su; Li-Ying Wang; Yu-Long Liang; Xi-Liang Zha

    2005-01-01

    AIM: Cell adhesion molecules and their signal molecules play a very important role in carcinogenesis. The aim of this study is to elucidate the role of these molecules and the signal molecules of integrins and E-cadherins, such as (focal adhesion kinase) FAK, (integrin linked kinase)ILK, and β-catenin in hepatocellular carcinoma cell apoptosis.METHODS: We first synthesized the small molecular compound, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and identified it, by element analysis and 1H NMR. To establish the apoptosis model of the SMMC-7721 hepatocellular carcinoma cell, we treated cells with DCVC in EBSS for different concentrations or for various length times in the presence of 20 μmol/L N,N-diphenyl-p-phenylenediamine,which blocks necrotic cell death and identified this model by flow cytometry and DNA ladder. Then we studied the changes of FAK, ILK, β-catenin, and PKB in this apoptotic model by Western blot.RESULTS: We found that the loss or decrease of cell adhesion signal molecules is an important reason in apoptosis of SMMC-7721 hepatocellular carcinoma cell and the apoptosis of SMMC-7721 cell was preceded by the loss or decrease of FAK, ILK, PKB, and β-catenin or the damage of cell-matrix and cell-cell adhesion.CONCLUSION: Our results suggested that the decrease of adhesion signal molecules, FAK, ILK, PKB, and β-catenin,could induce hepatocellular carcinoma cell apoptosis.

  9. Adductor Canal Block versus Femoral Nerve Block and Quadriceps Strength

    DEFF Research Database (Denmark)

    Jæger, Pia Therese; Nielsen, Zbigniew Jerzy Koscielniak; Henningsen, Lene Marianne;

    2013-01-01

    : The authors hypothesized that the adductor canal block (ACB), a predominant sensory blockade, reduces quadriceps strength compared with placebo (primary endpoint, area under the curve, 0.5-6 h), but less than the femoral nerve block (FNB; secondary endpoint). Other secondary endpoints were...

  10. The Protrusive Phase and Full Development of Integrin-Dependent Adhesions in Colon Epithelial Cells Require FAK- and ERKMediated Actin Spike Formation: Deregulation in Cancer Cells

    Directory of Open Access Journals (Sweden)

    Valerie G. Brunton

    2001-01-01

    Full Text Available Integrins play an important role in tumour progression by influencing cellular responses and matrix-dependent adhesion. However, the regulation of matrix-dependent adhesion assembly in epithelial cells is poorly understood. We have investigated the integrin and signalling requirements of cell-matrix adhesion assembly in colon carcinoma cells after plating on fibronectin. Adhesion assembly in these, and in the adenoma cells from which they were derived, was largely dependent on αvβ6 integrin and required phosphorylation of FAK on tyrosine-397. The rate of fibronectin-induced adhesion assembly and the expression of both αvβ6 integrin and FAK were increased during the adenoma-to-carcinoma transition. The matrix-dependent adhesion assembly process, particularly the final stages of complex protrusion that is required for optimal cell spreading, required the activity of extracellular signal-regulated kinase (ERK. Furthermore, phosphorylated ERK was targeted to newly forming cell-matrix adhesions in the carcinoma cells but not the adenoma cells, and inhibition of FAK-tyrosine-397 phosphorylation or MEK suppressed the appearance of phosphorylated ERK at peripheral sites. In addition, inhibition of MEK-ERK activation blocked the formation of peripheral actin microspikes that were necessary for the protrusive phase of cell-matrix adhesion assembly. Thus, MEK-ERK-dependent peripheral actin re-organization is required for the full development of integrin-induced adhesions and this pathway is stimulated in an in vitro model of colon cancer progression.

  11. Adhesives for orthodontic bracket bonding

    Directory of Open Access Journals (Sweden)

    Déborah Daniella Diniz Fonseca

    2010-04-01

    Full Text Available The advent of acid etching, introduced by Buonocore in 1955, brought the possibility of bonding between the bracket base and enamel, contributing to more esthetic and conservative orthodontics. This direct bracket bonding technique has brought benefits such as reduced cost and time in performing the treatment, as well as making it easier to perform oral hygiene. The aim of this study was to conduct a survey of published studies on orthodontic bracket bonding to dental enamel. It was verified that resin composites and glass ionomer are the most studied and researched materials for this purpose. Resin-modified glass ionomer, with its biocompatibility, capacity of releasing fluoride and no need for acid etching on the tooth structure, has become increasingly popular among dentists. However, due to the esthetic and mechanical properties of light polymerizable resin composite, it continues to be one of the adhesives of choice in the bracket bonding technique and its use is widely disseminated.

  12. Critical length scale controls adhesive wear mechanisms

    Science.gov (United States)

    Aghababaei, Ramin; Warner, Derek H.; Molinari, Jean-Francois

    2016-06-01

    The adhesive wear process remains one of the least understood areas of mechanics. While it has long been established that adhesive wear is a direct result of contacting surface asperities, an agreed upon understanding of how contacting asperities lead to wear debris particle has remained elusive. This has restricted adhesive wear prediction to empirical models with limited transferability. Here we show that discrepant observations and predictions of two distinct adhesive wear mechanisms can be reconciled into a unified framework. Using atomistic simulations with model interatomic potentials, we reveal a transition in the asperity wear mechanism when contact junctions fall below a critical length scale. A simple analytic model is formulated to predict the transition in both the simulation results and experiments. This new understanding may help expand use of computer modelling to explore adhesive wear processes and to advance physics-based wear laws without empirical coefficients.

  13. Dynamic analysis of two adhesively bonded rods

    Directory of Open Access Journals (Sweden)

    Kenneth L. Kuttler

    2009-07-01

    Full Text Available This work presents two models for the dynamic analysis of two rods that are adhesively bonded. The first model assumes that the adhesive is an elasto-plastic material and that complete debonding occurs when the stress reaches the yield limit. In the second model the degradation of the adhesive is described by the introduction of material damage. Failure occurs when the material is completely damaged, or the damage reaches a critical floor value. Both models are analyzed and the existence of a weak solution is established for the model with damage. In the quasistatic case, a new condition for adhesion is found as the limit of the adhesive thickness tends to zero.

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

    Science.gov (United States)

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

    2016-01-01

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

  15. Surface tension driven shaping of adhesive microfluidic channel walls

    DEFF Research Database (Denmark)

    Janting, Jakob; Storm, Elisabeth K.; Geschke, Oliver

    2005-01-01

    The feasibility of making microfluidic channels with different wall geometries using adjacent lines of dispensed adhesive between substrates has been studied. Important parameters for the geometry have been identified to be: surface tension (adhesive / substrates), adhesive viscosity / thixotropy...

  16. Comparison of the Fouling Release Properties of Hydrophobic Fluorinated and Hydrophilic PEGylated Block Copolymer Surfaces

    International Nuclear Information System (INIS)

    To understand the role of surface wettability in adhesion of cells, the attachment of two different marine algae was studied on hydrophobic and hydrophilic polymer surfaces. Adhesion of cells of the diatom Navicula and sporelings (young plants) of the green macroalga Ulva to an underwater surface is mainly by interactions between the surface and the adhesive exopolymers, which the cells secrete upon settlement and during subsequent colonization and growth. Two types of block copolymers, one with poly(ethylene glycol) side-chains and the other with liquid crystalline, fluorinated side-chains, were used to prepare the hydrophilic and hydrophobic surfaces, respectively. The formation of a liquid crystalline smectic phase in the latter inhibited molecular reorganization at the surface, which is generally an issue when a highly hydrophobic surface is in contact with water. The adhesion strength was assessed by the fraction of settled cells (Navicula) or biomass (Ulva) that detached from the surface in a water flow channel with a wall shear stress of 53 Pa. The two species exhibited opposite adhesion behavior on the same sets of surfaces. While Navicula cells released more easily from hydrophilic surfaces, Ulva sporelings showed higher removal from hydrophobic surfaces. This highlights the importance of differences in cell-surface interactions in determining the strength of adhesion of cells to substrates

  17. Multi-block and path modelling procedures

    DEFF Research Database (Denmark)

    Høskuldsson, Agnar

    2008-01-01

    The author has developed a unified theory of path and multi-block modelling of data. The data blocks are arranged in a directional path. Each data block can lead to one or more data blocks. It is assumed that there is given a collection of input data blocks. Each of them is supposed to describe one...... or more intermediate data blocks. The output data blocks are those that are at the ends of the paths and have no succeeding data blocks. The optimisation procedure finds weights for the input data blocks so that the size of the total loadings for the output data blocks are maximised. When the optimal...... weight vectors have been determined, the score and loading vectors for the data blocks in the path are determined. Appropriate adjustment of the data blocks is carried out at each step. Regression coefficients are computed for each data block that show how the data block is estimated by data blocks...

  18. Mechanisms of Staphylococcus epidermidis adhesion to model biomaterial surfaces: Establising a link between thrombosis and infection

    Science.gov (United States)

    Higashi, Julie Miyo

    Infections involving Staphylococcus epidermidis remain a life threatening complication associated with the use of polymer based cardiovascular devices. One of the critical steps in infection pathogenesis is the adhesion of the bacteria to the device surface. Currently, mechanisms of S. epidermidis adhesion are incompletely understood, but are thought to involve interactions between bacteria, device surface, and host blood elements in the form of adsorbed plasma proteins and surface adherent platelets. Our central hypothesis is that elements participating in thrombosis also promote S. epidermidis adhesion by specifically binding to the bacterial surface. The adhesion kinetics of S. epidermidis RP62A to host modified model biomaterial surface octadecyltrichlorosilane (OTS) under hydrodynamic shear conditions were characterized. Steady state adhesion to adsorbed proteins and surface adherent platelets was achieved at 90-120 minutes and 60-90 minutes, respectively. A dose response curve of S. epidermidis adhesion in the concentration range of 10sp7{-}10sp9 bac/mL resembled a multilayer adsorption isotherm. Increasing shear stress was found to LTA, and other LTA blocking agents significantly decreased S. epidermidis adhesion to the fibrin-platelet clots, suggesting that this interaction between S. epidermidis and fibrin-platelet clots is specific. Studies evaluated the adhesion of S. epidermidis to polymer immobilized heparin report conflicting results. Paulsson et al., showed that coagulase negative staphylococci adhered in comparable numbers to both immobilized heparin and nonheparinized surfaces, while exhibiting significantly greater adhesion to both surfaces than S. aureus. Preadsorption of the surfaces with specific heparin binding plasma proteins vitronectin, fibronectin, laminin, and collagen significantly increased adhesion. It was postulated that immobilized heparin contained binding sites for the plasma proteins, exposing bacteria binding domains of the

  19. Effect of hydroxyapatite surface morphology on cell adhesion.

    Science.gov (United States)

    Iwamoto, Takashi; Hieda, Yohki; Kogai, Yasumichi

    2016-12-01

    We obtained hydroxyapatite (HAp) materials as a block by mixing HAp nanoparticles and polymer, and then calcining the mixtures. The surface morphology of the HAp materials was tuned by varying heat treatment conditions. After calcining the mixtures at 1200 or 800°C for 4h, the surface morphology of the HAp materials was flat or convexo-concave, respectively. The flat surface morphology, which showed micrometer-ordered grain boundaries, was formed by the aggregation of HAp nanoparticles. On the other hand, the convexo-concave surface morphology resulted from the agglomeration of HAp nanoparticles after heat treatment at 800°C for 4h with nanometer-ordered particle size. We tested cell adhesion to HAp materials with flat or convexo-concave surface morphology and found that cells adhered well to the flat HAp materials but not to the convexo-concave HAp materials. This technique for selectively preparing HAp materials with flat or convexo-concave surface morphology was very easy because we merely mixed commercial HAp nanoparticles with polymer and then calcined the mixtures. As a result, the heat treatment temperature affected the surface morphology of our HAp materials, and their surface morphologies contributed to cell adhesion independently of other material properties. PMID:27612825

  20. 3D surface topology guides stem cell adhesion and differentiation.

    Science.gov (United States)

    Viswanathan, Priyalakshmi; Ondeck, Matthew G; Chirasatitsin, Somyot; Ngamkham, Kamolchanok; Reilly, Gwendolen C; Engler, Adam J; Battaglia, Giuseppe

    2015-06-01

    Polymerized high internal phase emulsion (polyHIPE) foams are extremely versatile materials for investigating cell-substrate interactions in vitro. Foam morphologies can be controlled by polymerization conditions to result in either open or closed pore structures with different levels of connectivity, consequently enabling the comparison between 2D and 3D matrices using the same substrate with identical surface chemistry conditions. Additionally, here we achieve the control of pore surface topology (i.e. how different ligands are clustered together) using amphiphilic block copolymers as emulsion stabilizers. We demonstrate that adhesion of human mesenchymal progenitor (hES-MP) cells cultured on polyHIPE foams is dependent on foam surface topology and chemistry but is independent of porosity and interconnectivity. We also demonstrate that the interconnectivity, architecture and surface topology of the foams has an effect on the osteogenic differentiation potential of hES-MP cells. Together these data demonstrate that the adhesive heterogeneity of a 3D scaffold could regulate not only mesenchymal stem cell attachment but also cell behavior in the absence of soluble growth factors.

  1. [Mechanisms of the stimulating effect of brain antibodies on the Ca2 current in the neuron membrane].

    Science.gov (United States)

    Solntseva, E I; Pozdniakova, A L; Savich, V; Khorvat, I; Iankovich, B

    1987-11-01

    Antibodies against rat brain microsomes induce a 16 +/- 3% increase in the amplitude of Ca-current (ICa) in snail neurons. Ca-ions block ICa in dose-dependent and potential-dependent manner. Antibodies against microsomes decrease the effectiveness of ICa blockade by Ca-ions: a 85 +/- 10% increase in ICa is observed and I-V curve is normalized. It is suggested that an enhancing effect of antibodies on ICa and the elimination of blocking Ca-effect on ICa are connected with the weakening of divalent cations binding by the anionic groups of calcium channels. PMID:2445395

  2. OPAL Various Lead Glass Blocks

    CERN Multimedia

    These lead glass blocks were part of a CERN detector called OPAL (one of the four experiments at the LEP particle detector). OPAL uses some 12 000 blocks of glass like this to measure particle energies in the electromagnetic calorimeter. This detector measured the energy deposited when electrons and photons were slowed down and stopped.

  3. Block storage subsystem performance analysis

    CERN Document Server

    CERN. Geneva

    2016-01-01

    You feel that your service is slow because of the storage subsystem? But there are too many abstraction layers between your software and the raw block device for you to debug all this pile... Let's dive on the platters and check out how the block storage sees your I/Os! We can even figure out what those patterns are meaning.

  4. Classical Virasoro irregular conformal block

    CERN Document Server

    Rim, Chaiho

    2015-01-01

    Virasoro irregular conformal block with arbitrary rank is obtained for the classical limit or equivalently Nekrasov-Shatashvili limit using the beta-deformed irregular matrix model (Penner-type matrix model for the irregular conformal block). The same result is derived using the generalized Mathieu equation which is equivalent to the loop equation of the irregular matrix model.

  5. A monoclonal antibody against leptin.

    Science.gov (United States)

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

    2012-10-01

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

  6. Surfactant functionalization induces robust, differential adhesion of tumor cells and blood cells to charged nanotube-coated biomaterials under flow.

    Science.gov (United States)

    Mitchell, Michael J; Castellanos, Carlos A; King, Michael R

    2015-07-01

    The metastatic spread of cancer cells from the primary tumor to distant sites leads to a poor prognosis in cancers originating from multiple organs. Increasing evidence has linked selectin-based adhesion between circulating tumor cells (CTCs) and endothelial cells of the microvasculature to metastatic dissemination, in a manner similar to leukocyte adhesion during inflammation. Functionalized biomaterial surfaces hold promise as a diagnostic tool to separate CTCs and potentially treat metastasis, utilizing antibody and selectin-mediated interactions for cell capture under flow. However, capture at high purity levels is challenged by the fact that CTCs and leukocytes both possess selectin ligands. Here, a straightforward technique to functionalize and alter the charge of naturally occurring halloysite nanotubes using surfactants is reported to induce robust, differential adhesion of tumor cells and blood cells to nanotube-coated surfaces under flow. Negatively charged sodium dodecanoate-functionalized nanotubes simultaneously enhanced tumor cell capture while negating leukocyte adhesion, both in the presence and absence of adhesion proteins, and can be utilized to isolate circulating tumor cells regardless of biomarker expression. Conversely, diminishing nanotube charge via functionalization with decyltrimethylammonium bromide both abolished tumor cell capture while promoting leukocyte adhesion.

  7. Enhanced human bone marrow stromal cell affinity for modified poly(L-lactide) surfaces by the upregulation of adhesion molecular genes.

    Science.gov (United States)

    Mao, Xueli; Peng, Hui; Ling, Junqi; Friis, Thor; Whittaker, Andrew K; Crawford, Ross; Xiao, Yin

    2009-12-01

    To enhance and regulate cell affinity for poly (L-lactic acid) (PLLA) based materials, two hydrophilic ligands, poly (ethylene glycol) (PEG) and poly (L-lysine) (PLL), were used to develop triblock copolymers: methoxy-terminated poly (ethylene glycol)-block-poly (L-lactide)-block-poly (L-lysine) (MPEG-b-PLLA-b-PLL) in order to regulate protein absorption and cell adhesion. Bone marrow stromal cells (BMSCs) were cultured on different composition of MPEG-b-PLLA-b-PLL copolymer films to determine the effect of modified polymer surfaces on BMSC attachment. To understand the molecular mechanism governing the initial cell adhesion on difference polymer surfaces, the mRNA expression of 84 human extracellular matrix (ECM) and adhesion molecules was analysed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). It was found that down regulation of adhesion molecules was responsible for the impaired BMSC attachment on PLLA surface. MPEG-b-PLLA-b-PLL copolymer films improved significantly the cell adhesion and cytoskeleton expression by upregulation of relevant molecule genes significantly. Six adhesion genes (CDH1, ITGL, NCAM1, SGCE, COL16A1, and LAMA3) were most significantly influenced by the modified PLLA surfaces. In summary, polymer surfaces altered adhesion molecule gene expression of BMSCs, which consequently regulated cell initial attachment on modified PLLA surfaces. PMID:19796804

  8. Engineering antibodies by yeast display.

    Science.gov (United States)

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

    2012-10-15

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

  9. Antiphospholipid Antibody and Antiphospholipid Syndrome

    Institute of Scientific and Technical Information of China (English)

    吴竞生

    2008-01-01

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

  10. Fully human antagonistic antibodies against CCR4 potently inhibit cell signaling and chemotaxis.

    Directory of Open Access Journals (Sweden)

    Urs B Hagemann

    Full Text Available CC chemokine receptor 4 (CCR4 represents a potentially important target for cancer immunotherapy due to its expression on tumor infiltrating immune cells including regulatory T cells (Tregs and on tumor cells in several cancer types and its role in metastasis.Using phage display, human antibody library, affinity maturation and a cell-based antibody selection strategy, the antibody variants against human CCR4 were generated. These antibodies effectively competed with ligand binding, were able to block ligand-induced signaling and cell migration, and demonstrated efficient killing of CCR4-positive tumor cells via ADCC and phagocytosis. In a mouse model of human T-cell lymphoma, significant survival benefit was demonstrated for animals treated with the newly selected anti-CCR4 antibodies.For the first time, successful generation of anti- G-protein coupled chemokine receptor (GPCR antibodies using human non-immune library and phage display on GPCR-expressing cells was demonstrated. The generated anti-CCR4 antibodies possess a dual mode of action (inhibition of ligand-induced signaling and antibody-directed tumor cell killing. The data demonstrate that the anti-tumor activity in vivo is mediated, at least in part, through Fc-receptor dependent effector mechanisms, such as ADCC and phagocytosis. Anti-CC chemokine receptor 4 antibodies inhibiting receptor signaling have potential as immunomodulatory antibodies for cancer.

  11. The Shamrock lumbar plexus block

    DEFF Research Database (Denmark)

    Sauter, Axel R; Ullensvang, Kyrre; Niemi, Geir;

    2015-01-01

    BACKGROUND: The Shamrock technique is a new method for ultrasound-guided lumbar plexus blockade. Data on the optimal local anaesthetic dose are not available. OBJECTIVE: The objective of this study is to estimate the effective dose of ropivacaine 0.5% for a Shamrock lumbar plexus block. DESIGN: A...... prospective dose-finding study using Dixon's up-and-down sequential method. SETTING: University Hospital Orthopaedic Anaesthesia Unit. INTERVENTION: Shamrock lumbar plexus block performance and block assessment were scheduled preoperatively. Ropivacaine 0.5% was titrated with the Dixon and Massey up......-and-down method using a stepwise change of 5 ml in each consecutive patient. Combined blocks of the femoral, the lateral femoral cutaneous and the obturator nerve were prerequisite for a successful lumbar plexus block. PATIENTS: Thirty patients scheduled for lower limb orthopaedic surgery completed the study...

  12. Demonstration of immunochemical identity between the nerve growth factor-inducible large external (NILE) glycoprotein and the cell adhesion molecule L1

    DEFF Research Database (Denmark)

    Bock, E; Richter-Landsberg, C; Faissner, A;

    1985-01-01

    The nerve growth factor-inducible large external (NILE) glycoprotein and the neural cell adhesion molecule L1 were shown to be immunochemically identical. Immunoprecipitation with L1 and NILE antibodies of [3H]fucose-labeled material from culture supernatants and detergent extracts of NGF......]methionine-labeled early post-natal cerebellar cell cultures or [3H]fucose-labeled NGF-treated PC12 cells, all immunoreactivity for NILE antibody could be removed by pre-clearing with L1 antibody and vice versa....

  13. A method for visualizing surface-exposed and internal PfEMP1 adhesion antigens in Plasmodium falciparum infected erythrocytes

    DEFF Research Database (Denmark)

    Bengtsson, Dominique; Sowa, Kordai M; Salanti, Ali;

    2008-01-01

    BACKGROUND: The insertion of parasite antigens into the host erythrocyte membrane and the structure and distribution of Plasmodium falciparum adhesion receptors on that membrane are poorly understood. Laser scanning confocal microscopy (LSCM) and a novel labelling and fixation method have been used......-ionic detergent to permit access of antibodies to internal parasite antigens. Differentiation between surface and internal antigens is achieved using antibodies labelled with different fluorochromes and confocal microscopy RESULTS: Surface exposed PfEMP1 is first detectable by antibodies at the trophozoite stage...

  14. Antibody protection against botulinum neurotoxin intoxication in mice.

    Science.gov (United States)

    Cheng, Luisa W; Stanker, Larry H; Henderson, Thomas D; Lou, Jianlong; Marks, James D

    2009-10-01

    Adulteration of food or feed with any of the seven serotypes of botulinum neurotoxin (BoNT) is a potential bioterrorism concern. Currently, there is strong interest in the development of detection reagents, vaccines, therapeutics, and other countermeasures. A sensitive immunoassay for detecting BoNT serotype A (BoNT/A), based on monoclonal antibodies (MAbs) F1-2 and F1-40, has been developed and used in complex matrices. The epitope for F1-2 has been mapped to the heavy chain of BoNT/A, and the epitope of F1-40 has been mapped to the light chain. The ability of these MAbs to provide therapeutic protection against BoNT/A intoxication in mouse intravenous and oral intoxication models was tested. High dosages of individual MAbs protected mice well both pre- and postexposure to BoNT/A holotoxin. A combination therapy consisting of antibodies against both the light and heavy chains of the toxin, however, significantly increased protection, even at a lower MAb dosage. An in vitro peptide assay for measuring toxin activity showed that pretreatment of toxin with these MAbs did not block catalytic activity but instead blocked toxin entry into primary and cultured neuronal cells. The timing of antibody rescue in the mouse intoxication models revealed windows of opportunity for antibody therapeutic treatment that correlated well with the biologic half-life of the toxin in the serum. Knowledge of BoNT intoxication and antibody clearance in these mouse models and understanding of the pharmacokinetics of BoNT are invaluable for future development of antibodies and therapeutics against intoxication by BoNT.

  15. Antibody protection reveals extended epitopes on the human TSH receptor.

    Directory of Open Access Journals (Sweden)

    Rauf Latif

    Full Text Available Stimulating, and some blocking, antibodies to the TSH receptor (TSHR have conformation-dependent epitopes reported to involve primarily the leucine rich repeat region of the ectodomain (LRD. However, successful crystallization of TSHR residues 22-260 has omitted important extracellular non-LRD residues including the hinge region which connects the TSHR ectodomain to the transmembrane domain and which is involved in ligand induced signal transduction. The aim of the present study, therefore, was to determine if TSHR antibodies (TSHR-Abs have non-LRD binding sites outside the LRD. To obtain this information we employed the method of epitope protection in which we first protected TSHR residues 1-412 with intact TSHR antibodies and then enzymatically digested the unprotected residues. Those peptides remaining were subsequently delineated by mass spectrometry. Fourteen out of 23 of the reported stimulating monoclonal TSHR-Ab crystal contact residues were protected by this technique which may reflect the higher binding energies of certain residues detected in this approach. Comparing the protected epitopes of two stimulating TSHR-Abs we found both similarities and differences but both antibodies also contacted the hinge region and the amino terminus of the TSHR following the signal peptide and encompassing cysteine box 1 which has previously been shown to be important for TSH binding and activation. A monoclonal blocking TSHR antibody revealed a similar pattern of binding regions but the residues that it contacted on the LRD were again distinct. These data demonstrated that conformationally dependent TSHR-Abs had epitopes not confined to the LRDs but also incorporated epitopes not revealed in the available crystal structure. Furthermore, the data also indicated that in addition to overlapping contact regions within the LRD, there are unique epitope patterns for each of the antibodies which may contribute to their functional heterogeneity.

  16. Antibody protection reveals extended epitopes on the human TSH receptor.

    Science.gov (United States)

    Latif, Rauf; Teixeira, Avelino; Michalek, Krzysztof; Ali, M Rejwan; Schlesinger, Max; Baliram, Ramkumarie; Morshed, Syed A; Davies, Terry F

    2012-01-01

    Stimulating, and some blocking, antibodies to the TSH receptor (TSHR) have conformation-dependent epitopes reported to involve primarily the leucine rich repeat region of the ectodomain (LRD). However, successful crystallization of TSHR residues 22-260 has omitted important extracellular non-LRD residues including the hinge region which connects the TSHR ectodomain to the transmembrane domain and which is involved in ligand induced signal transduction. The aim of the present study, therefore, was to determine if TSHR antibodies (TSHR-Abs) have non-LRD binding sites outside the LRD. To obtain this information we employed the method of epitope protection in which we first protected TSHR residues 1-412 with intact TSHR antibodies and then enzymatically digested the unprotected residues. Those peptides remaining were subsequently delineated by mass spectrometry. Fourteen out of 23 of the reported stimulating monoclonal TSHR-Ab crystal contact residues were protected by this technique which may reflect the higher binding energies of certain residues detected in this approach. Comparing the protected epitopes of two stimulating TSHR-Abs we found both similarities and differences but both antibodies also contacted the hinge region and the amino terminus of the TSHR following the signal peptide and encompassing cysteine box 1 which has previously been shown to be important for TSH binding and activation. A monoclonal blocking TSHR antibody revealed a similar pattern of binding regions but the residues that it contacted on the LRD were again distinct. These data demonstrated that conformationally dependent TSHR-Abs had epitopes not confined to the LRDs but also incorporated epitopes not revealed in the available crystal structure. Furthermore, the data also indicated that in addition to overlapping contact regions within the LRD, there are unique epitope patterns for each of the antibodies which may contribute to their functional heterogeneity. PMID:22957097

  17. Glycosylation inhibitors efficiently inhibit P-selectin-mediated cell adhesion to endothelial cells.

    Science.gov (United States)

    Ghoshal, Pushpankur; Rajendran, Mythilypriya; Odo, Nadine; Ikuta, Tohru

    2014-01-01

    Adhesion molecules play a critical role in the adhesive interactions of multiple cell types in sickle cell disease (SCD). We previously showed that anti-P-selectin aptamer efficiently inhibits cell adhesion to endothelial cells (ECs) and permits SCD mice to survive hypoxic stress. In an effort to discover new mechanisms with which to inhibit P-selectin, we examined the role of glycosylation. P-selectin is a 90 kDa protein but was found to migrate as 90 and 140 kDa bands on gel electrophoresis. When P-selectin isolated from ECs was digested with peptide N-glycosidase F, but not O-glycosidase, the 140 kDa band was lost and the 90 kDa band was enhanced. Treatment of ECs with tunicamycin, an N-glycosylation inhibitor, suppressed CD62P (P-selectin) expression on the cell surface as well as the 140 kDa form in the cytoplasm. These results indicate that the 140 kDa band is N-glycosylated and glycosylation is critical for cell surface expression of P-selectin in ECs. Thrombin, which stimulates P-selectin expression on ECs, induced AKT phosphorylation, whereas tunicamycin inhibited AKT phosphorylation, suggesting that AKT signaling is involved in the tunicamycin-mediated inhibition of P-selectin expression. Importantly, the adhesion of sickle red blood cells (sRBCs) and leukocytes to ECs induced by thrombin or hypoxia was markedly inhibited by two structurally distinct glycosylation inhibitors; the levels of which were comparable to that of a P-selectin monoclonal antibody which most strongly inhibited cell adhesion in vivo. Knockdown studies of P-selectin using short-hairpin RNAs in ECs suppressed sRBC adhesion, indicating a legitimate role for P-selectin in sRBC adhesion. Together, these results demonstrate that P-selectin expression on ECs is regulated in part by glycosylation mechanisms and that glycosylation inhibitors efficiently reduce the adhesion of sRBCs and leukocytes to ECs. Glycosylation inhibitors may lead to a novel therapy which inhibits cell adhesion in SCD.

  18. Molecular recognition between glyconectins as an adhesion self-assembly pathway to multicellularity.

    Science.gov (United States)

    Misevic, Gradimir N; Guerardel, Yann; Sumanovski, Lazar T; Slomianny, Marie-Christine; Demarty, Maurice; Ripoll, Camille; Karamanos, Yannis; Maes, Emmanuel; Popescu, Octavian; Strecker, Gerard

    2004-04-01

    The appearance of multicellular forms of life has been tightly coupled to the ability of an organism to retain its own anatomical integrity and to distinguish self from non-self. Large glycoconjugates, which make up the outermost cell surface layer of all Metazoans, are the primary candidates for the primordial adhesion and recognition functions in biological self-assembly systems. Atomic force microscopy experiments demonstrated that the binding strength between a single pair of Porifera cell surface glyconectin 1 glycoconjugates from Microciona prolifera can hold the weight of 1600 cells, proving their adhesion functions. Here, measurement of molecular self-recognition of glyconectins (GNs) purified from three Porifera species was used as an experimental model for primordial xenogeneic self/non-self discrimination. Physicochemical and biochemical characterization of the three glyconectins, their glycans, and peptides using gel electrophoresis, ultracentrifugation, NMR, mass spectrometry, glycosaminoglycan-degrading enzyme treatment, amino acid and carbohydrate analyses, and peptide mapping showed that GNs define a new family of proteoglycan-like molecules exhibiting species-specific structures with complex and repetitive acidic carbohydrate motives different from the classical proteoglycans and mucins. In functional self-assembly color-coded bead, cell, and blotting assays, glyconectins displayed species-specific recognition and adhesion. Affinity-purified monospecific polyclonal antibodies prepared against GN1, -2, and -3 glycans selectively inhibited cell adhesion of the respective sponge species. These results together with species-specific coaggregation of GN carbohydrate-coated beads with cells showed that GN glycans are functional in cell recognition and adhesion. The specificity of carbohydrate-mediated homophilic GN interactions in Porifera approaches the binding selectivity of the evolutionarily advanced immunoglobulin superfamily. Xenoselectivity of

  19. A Novel Adhesion Index for Verifying the Extent of Adhesion for the Extensor Digitorum Communis in Patients with Metacarpal Fractures

    Science.gov (United States)

    Lai, Ting-Yu; Chen, Hsiao-I; Shih, Cho-Chiang; Kuo, Li-Chieh; Hsu, Hsiu-Yun; Huang, Chih-Chung

    2016-01-01

    This study aims to determine if the relative displacement between the extensor digitorum communis (EDC) tendon and its surrounding tissues can be used as an adhesion index (AI) for assessing adhesion in metacarpal fractures by comparing two clinical measures, namely single-digit-force and extensor lag (i.e., the difference between passive extension and full active extension). The Fisher–Tippett block-matching method and a Kalman-filter algorithm were used to determine the relative displacements in 39 healthy subjects and 8 patients with metacarpal fractures. A goniometer was used to measure the extensor lag, and a force sensor was used to measure the single-digit-force. Measurements were obtained twice for each patient to evaluate the performance of the AI in assessing the progress of rehabilitation. The Pearson correlation coefficient was calculated to quantify the various correlations between the AI, extensor lag, and single-digit-force. The results showed strong correlations between the AI and the extensor lag, the AI and the single-digit-force, and the extensor lag and the single-digit-force (r = 0.718, −0.849, and −0.741; P = 0.002, P AI in the patients gradually decreased after continuous rehabilitation, but remained higher than that of healthy participants. PMID:27492808

  20. Comparative dynamics of retrograde actin flow and focal adhesions: formation of nascent adhesions triggers transition from fast to slow flow.

    Directory of Open Access Journals (Sweden)

    Antonina Y Alexandrova

    Full Text Available Dynamic actin network at the leading edge of the cell is linked to the extracellular matrix through focal adhesions (FAs, and at the same time it undergoes retrograde flow with different dynamics in two distinct zones: the lamellipodium (peripheral zone of fast flow, and the lamellum (zone of slow flow located between the lamellipodium and the cell body. Cell migration involves expansion of both the lamellipodium and the lamellum, as well as formation of new FAs, but it is largely unknown how the position of the boundary between the two flow zones is defined, and how FAs and actin flow mutually influence each other. We investigated dynamic relationship between focal adhesions and the boundary between the two flow zones in spreading cells. Nascent FAs first appeared in the lamellipodium. Within seconds after the formation of new FAs, the rate of actin flow decreased locally, and the lamellipodium/lamellum boundary advanced towards the new FAs. Blocking fast actin flow with cytochalasin D resulted in rapid dissolution of nascent FAs. In the absence of FAs (spreading on poly-L-lysine-coated surfaces retrograde flow was uniform and the velocity transition was not observed. We conclude that formation of FAs depends on actin dynamics, and in its turn, affects the dynamics of actin flow by triggering transition from fast to slow flow. Extension of the cell edge thus proceeds through a cycle of lamellipodium protrusion, formation of new FAs, advance of the lamellum, and protrusion of the lamellipodium from the new base.