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Binding Inhibition (binding + inhibition)
Selected AbstractsEpitope mapping of canine distemper virus phosphoprotein by monoclonal antibodiesMICROBIOLOGY AND IMMUNOLOGY, Issue 12 2009Akihiro Sugai ABSTRACT The gene for phosphoprotein (P) of CDV encodes three different proteins, P, V, and C. The P protein is involved in viral gene transcription and replication. In the present study, we produced MAbs against a unique domain of the CDV-P protein, from aa 232 to 507, and determined their antigenic sites. By immunizing BALB/c mice with the recombinant P protein-specific fragment, we obtained six MAbs. Competitive binding inhibition assays revealed that they recognized two distinct regions of the P protein. Western blot analysis and immunofluorescence assays using deletion mutants of the unique C-terminus of the CDV-P protein revealed that all MAbs recognized a central short region (aa 233,303) of the CDV-P protein. In addition, linear and conformational epitopes have been determined, and at least four antigenic sites exist in the P protein central region. Furthermore, four of the MAbs were found to react with the P protein of recent Japanese field isolates but not with that of the older CDV strains, including a vaccine strain. Thus, these MAbs could be clinically useful for quick diagnosis during the CDV outbreaks. [source] Wound healing effects of noni (Morinda citrifolia L.) leaves: a mechanism involving its PDGF/A2A receptor ligand binding and promotion of wound closurePHYTOTHERAPY RESEARCH, Issue 10 2010Afa Palu Abstract Morinda citrifolia L. (Rubiaceae) commonly known as noni, has been used in Polynesia by traditional healers for the treatment of cuts, bruises and wounds. Our objective was to investigate the wound-healing mechanisms of the noni leaf. The investigations of its wound-healing mechanisms were carried out using fresh noni leaf juice (NLJ), noni leaf ethanol extract (NLEE) and its methanol (MFEE) and hexane (HFEE) fractions on the PDGF and A2A receptors in vitro and topically in mice. Fresh noni leaf juice showed significant affinity to PDGF receptors, and displayed 166% binding inhibition of the ligand binding to its receptors, while at the same concentration, it only had 7% inhibition of the ligand binding to the A2A receptors. NLEE, HFEE and MFEE showed significant affinity to A2A receptors, concentration dependently, with IC50 values of 34.1, 42.9 and 86.7,,g/mL, respectively. However, MFEE significantly increased wound closure and reduced the half closure time in mice with a CT50 of 5.4 ± 0.2 days compared with control (p < 0.05). These results suggest that noni leaf significantly accelerated wound healing in mice via its ligand binding to the PDGF and A2A receptors as its probable mechanisms of wound-healing and also support its traditional usage for wound-healing in Polynesia. Copyright © 2010 John Wiley & Sons, Ltd. [source] Albumin-Coated Tympanostomy Tubes: Prospective, Double-Blind Clinical Study,THE LARYNGOSCOPE, Issue 11 2004Teemu J. Kinnari MD Abstract Objectives: Coating an implant with albumin prevents adhesion of proteins, bacteria, and platelets and thus may lead to its improved and prolonged function. Previously, we have demonstrated the inhibition of binding of fibronectin, one of the most adhesive glycoproteins, on human serum albumin (HSA)-coated tympanostomy tubes and the durability of this binding inhibition in a 8-month trial. We have also demonstrated that the HSA coating inhibits the binding of Staphylococcus aureus and Pseudomonas aeruginosa to titanium plates. This prospective study evaluated the effect of albumin coating on tympanostomy tube sequelae and on the outcome of tympanostomized patients. Study Design: Double-blind, prospective, randomized clinical trial. Methods: Two otolaryngological centers in southern Finland enrolled 179 pediatric patients. Number of tube occlusions and otorrhea and tube ventilation time in the ears with HSA-coated titanium tympanostomy tubes were compared with the contralateral ear with its uncoated, otherwise identical titanium tube during a 9-month follow-up period. Results: In HSA-coated tubes, average ventilation time was slightly longer and the number of early tube occlusions significantly less (P < .05). Moreover, in patients with perioperative bleeding, the coating prolonged average ventilation time of tympanostomy tubes significantly (P < .05). Conclusions: HSA coating reduces early tube occlusions by preventing adherence of blood and secretion. [source] Safety and efficacy of meningococcal c vaccination in juvenile idiopathic arthritisARTHRITIS & RHEUMATISM, Issue 2 2007Evelien Zonneveld-Huijssoon Objective To determine whether vaccinations aggravate the course of autoimmune diseases such as juvenile idiopathic arthritis (JIA) and whether the immune response to vaccinations may be hampered by immunosuppressive therapy for the underlying disease. Methods In this multicenter cohort study, 234 patients with JIA (ages 1,19 years) were vaccinated with meningococcal serogroup C (MenC) conjugate to protect against serogroup C disease (caused by Neisseria meningitidis). Patients were followed up for disease activity for 1 year, from 6 months before until 6 months after vaccination. IgG antibody titers against MenC polysaccharide and the tetanus carrier protein were determined by enzyme-linked immunosorbent assay and toxin binding inhibition assay, respectively. A serum bactericidal assay was performed to determine the function of the anti-MenC antibodies. Results No change in values for any of the 6 components of the core set criteria for juvenile arthritis disease activity was seen after MenC vaccination. Moreover, no increase in the frequency of disease relapse was detected. Mean anti-MenC IgG concentrations in JIA patients rose significantly within 6,12 weeks after vaccination. Of 157 patients tested, 153 were able to mount anti-MenC IgG serum levels >2 ,g/ml, including patients receiving highly immunosuppressive medication. The 4 patients with a lower anti-MenC antibody response displayed sufficient bactericidal activity despite receiving highly immunosuppressive medication. Conclusion The MenC conjugate vaccine does not aggravate JIA disease activity or increase relapse frequency and results in adequate antibody levels, even in patients receiving highly immunosuppressive medication. Therefore, patients with JIA can be vaccinated safely and effectively with the MenC conjugate. [source] Cell-death-inducing monoclonal antibodies raised against DT40 tumor cells: Identification of chicken transferrin receptor as a novel cell-death receptorCANCER SCIENCE, Issue 5 2008Yoshiya Ohno We obtained unique cell-death-inducing monoclonal antibodies (mAbs) named D18 and D19 against chicken DT40 cells. D18 and D19 caused several signs of apoptosis, such as exposed phosphatidyl serine on the cell surface, a sub G0/G1 peak, and DNA fragmentation, and inhibited the proliferation of DT40 cells. Flow cytometric and immunohistological analyses of various normal chicken tissues revealed the expression of the antigen recognized by these mAbs to be restricted to cells in lymphoid organs including bone marrow and bursa of fabricius, and to cells in some epithelial tissues. The cell death induced by the mAbs progressed through a mitochondrial pathway with loss of mitochondrial membrane potential. Apoptosis is generally characterized by cell shrinking; however, D18 and D19 elicited swelling, which preceded the cell death. We analyzed the antigen immunoprecipitated by the mAbs, and identified a 90- to 100-kDa cell-surface glycoprotein as the chicken transferrin receptor (TfR). Epitopes recognized by the two mAbs were confirmed to be different by the binding inhibition assay. The reactivity of the mAbs against DT40 cells was not inhibited by excess chicken serum, suggesting that the cell death induced by D18 and D19 was not caused by inhibition of the binding of transferrin (Tf) to chicken TfR. Since D18 and D19 have induced cell death in human embryonic kidney cells transfected with cDNA of the full-length chicken TfR, we expect human TfR to be a promising target in antibody therapy for various human malignancies. (Cancer Sci 2008; 99: 894,900) [source] Characterization of thyroglobulin epitopes in Sardinian adults and juveniles with Hashimoto's thyroiditis: evidence against a major effect of age and genetic background on B-cell epitopesCLINICAL ENDOCRINOLOGY, Issue 1 2010Francesco Latrofa Summary Background, Using recombinant human monoclonal thyroglobulin antibodies expressed as Fab molecules (TgAb-Fab), we have recently confirmed the restriction of Tg epitopes in Hashimoto's thyroiditis (HT). Objective, To investigate Tg epitopes of serum TgAb in HT adults and HT juveniles from a geographically isolated area (Sardinia). Design and Patients, Serum TgAb of 39 Sardinian HT adults, 53 Sardinian HT juveniles and 45 non-Sardinian HT adults were evaluated. The binding of serum TgAb to Tg in ELISA was inhibited by four recombinant human TgAb-Fab, identifying Tg epitopic regions A,D. The percentage of Tg binding inhibition was calculated comparing the binding of serum TgAb in presence of each TgAb-Fab with that in its absence. Results, In the whole cohort of 137 patients, A region TgAb-Fab induced the highest levels of inhibition (55·3 ± 17·8%) (mean ± SD). Lower levels of inhibition were induced by TgAb-Fab of regions B (27·8 ± 25·8%), C (26·8 ± 24·6%) and D (17·5 ± 18·4%). In Sardinian HT adults inhibition by TgAb-Fab of regions A, B and C were comparable to Sardinian HT juveniles; the marginal D region TgAb-Fab induced a slightly higher inhibition (22·1 vs. 13·8%; P = 0·034) in the former than in the latter group. In Sardinian and non-Sardinian HT adults inhibitions by the four TgAb-Fab were similar. Conclusions, In HT, the Tg epitope pattern of serum TgAb was similar in juveniles and adults from a geographically restricted area and in two adult populations from different geographical areas. Thus, in HT, neither age nor genetic background appear to influence B-cell epitopes. [source] | ||||||||||