The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Shozo Izui - One of the best experts on this subject based on the ideXlab platform.
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a critical role for sialylation in cryoglobulin activity of murine igg3 monoclonal antibodies
Journal of Immunology, 2005Co-Authors: Yasuhiro Kuroda, Aki Kuroki, Munehiro Nakata, Shuichi Kikuchi, Takaaki Funase, Shozo IzuiAbstract:Cryoprecipitating IgG3 autoantibodies have been shown to play a significant role in the development of murine lupus-like autoimmune syndrome. However, the structural basis of IgG3 Cryoprecipitation still remains to be defined. In view of the implication of positively charged amino acid residues present in variable regions in IgG3 cryoglobulin activity, we explored the role of terminal sialic acids in oligosaccharide side chains for the cryogenic activity of IgG3 mAb. Comparative oligosaccharide structural analysis of different cryogenic and non-cryogenic IgG3 mAb showed an inverse correlation between the extent of sialylation and cryogenic activity. The inhibitory role of sialylation was further confirmed by the demonstration of enrichment of less and more sialylated IgG3 in cryoprecipitated and noncryoprecipitated fractions, respectively, separated from four different cryogenic IgG3 mAb. Significantly, the sialic acid contents of the latter fraction became comparable to those of non-cryogenic IgG3 mAb. Finally, we observed that highly sialylated non-cryogenic IgG3 mAb was more potent in the inhibition of Cryoprecipitation of cryogenic IgG3 mAb. Our results thus suggest that the content of negatively charged sialic acids in oligosaccharide side chains is one of the critical factors to determine IgG3 cryoglobulin activity, along with amino acid sequences of the IgG3 variable regions.
Leopoldo Paolo Pucillo - One of the best experts on this subject based on the ideXlab platform.
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cl regulates cryoglobulin structure a new hypothesis for the physiopathological mechanism of temperature non dependent Cryoprecipitation
Clinical Chemistry and Laboratory Medicine, 2004Co-Authors: Enrico Di Stasio, Milvia Casato, Patrizia Bizzarri, Antonio Galtieri, Massimo Fiorilli, Leopoldo Paolo PucilloAbstract:Cryoglobulins are pathological cold-precipitable immunoglobulins associated with a number of infectious, autoimmune and neoplastic disorders. Patients, when exposed to low temperatures, show symptoms related to intravascular precipitation of such immunoglobulins. The formation of cryoaggregates induced by exposure to cold temperature is the key pathogenetic mechanism. The subsequent intravascular precipitation can account for some clinical signs of peripheral vasculitis, but fails to explain the precipitation of cryoglobulins in regions where no significant temperature changes take place. We studied, in vitro, the activity of different ions on temperature-dependent aggregation of cryoglobulins and found that the concentration of Cl- present in solution is the most important variable that controls the size and the rate of formation of aggregates, both at low temperature and at 37 degrees C. We suggest that chloride anion could be the most important factor involved in the pathogenesis of events in visceral regions, such as in the kidneys, where no temperature changes occur but where the local Cl- concentration changes to maintain blood electrolytic homeostasis and acid-basic equilibrium. Moreover, identification of a specific structural domain responsible for Cl- binding may provide new targets for drugs selectively designed to interfere with cryoglobulin aggregation.
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Analysis of the dynamics of cryoaggregation by light-scattering spectrometry
'Walter de Gruyter GmbH', 2003Co-Authors: E. Di Stasio, Milvia Casato, Patrizia Bizzarri, Antonio Galtieri, Massimo Fiorilli, Maurizio Bove, Bruno Giardina, Leopoldo Paolo PucilloAbstract:Cryoglobulins are proteins that precipitate at temperatures below 37 °C. Cold-induced precipitation of proteins may occur in vivo secondary to several important diseases, and lead to pathological manifestations involving different organs. Cryoprecipitation may be observed in vitro by exposing serum samples, supposed to contain cryoglobulins, to low temperatures, but this needs several days to occur. Protein-protein interactions leading to Cryoprecipitation are still poorly understood and the knowledge of the underlying mechanism may be relevant to the understanding of the onset of pathological manifestations. Using light-scattering spectrometry, we studied Cryoprecipitation occurring in vitro at different temperatures and cryoglobulin concentrations. We describe the kinetics of the cold-induced precipitation of mixed cryoglobulins, measured as increase in turbidity. The plots obtained demonstrate that the Cryoprecipitation did not occur as a single-step reaction, but consisted of four distinct phases where both temperature and cryoglobulin concentration affected the immune complexes formation. Light scatter spectrometry may provide a simple, sensitive and rapid method for the detection of cryoglobulins
N Stojanovic - One of the best experts on this subject based on the ideXlab platform.
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evaluation of fibrin glue prepared by recycled Cryoprecipitation in experimental liver surgery
Experimental Hematology, 2000Co-Authors: Bela Balint, Ibolja Cernak, Marijana Petakov, Diana Bugarski, Jovan Taseski, A Nesic, N StojanovicAbstract:Abstract Fibrin glue (FG) is a two component biologic system with adhesive, sealant and topical hemostatic properties, containing fibrinogen, factor XIII, fibronectin, thrombin, some antifibrinolytic agent and ionized calcium. The purpose of the study was to evaluate the hemostatic effectiveness of FG prepared by a modification of Cryoprecipitation technique in experimental rat liver surgery. FG component 1 was prepared by triple or "recycled" Cryoprecipitation method from single-donor plasma. Rats subjected to liver incision, partial and total lobectomy were treated with FG on the surgical cut surface or underwent standard surgical technique and the efficacy of the FG-treatment was evaluated on the basis of the 24-hour survival ratio and peripheral blood hematological parameters. The mean values of fibrinogen, FXIII, fibronectin and horizontal tensile strength of FG were 54.2 ± 19.9 g/l, 8.03 ± 2.3 IU/ml, 3103.1 ± 148.9 mg/l, and 1.076 ± 0.18 N/cm 2 , respectively. The survival of FG-treated rats subjected to partial and total lobectomy was significantly higher in comparison to the FG-nontreated animals, accompanied with higher values of red blood cell counts, hemoglobin concentration, as well as hematocrit. The survival of animals subjected to liver incision was not significantly different, however the differences in hematological parameters were significant in favor FG-treated animals. The presented results demonstrated that using "recycled" Cryoprecipitation it is possible to obtain high quality single-donor FG with successful hemostatic therapeutical effects, as confirmed in the experimental rat liver surgery.
Yasuhiro Kuroda - One of the best experts on this subject based on the ideXlab platform.
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a critical role for sialylation in cryoglobulin activity of murine igg3 monoclonal antibodies
Journal of Immunology, 2005Co-Authors: Yasuhiro Kuroda, Aki Kuroki, Munehiro Nakata, Shuichi Kikuchi, Takaaki Funase, Shozo IzuiAbstract:Cryoprecipitating IgG3 autoantibodies have been shown to play a significant role in the development of murine lupus-like autoimmune syndrome. However, the structural basis of IgG3 Cryoprecipitation still remains to be defined. In view of the implication of positively charged amino acid residues present in variable regions in IgG3 cryoglobulin activity, we explored the role of terminal sialic acids in oligosaccharide side chains for the cryogenic activity of IgG3 mAb. Comparative oligosaccharide structural analysis of different cryogenic and non-cryogenic IgG3 mAb showed an inverse correlation between the extent of sialylation and cryogenic activity. The inhibitory role of sialylation was further confirmed by the demonstration of enrichment of less and more sialylated IgG3 in cryoprecipitated and noncryoprecipitated fractions, respectively, separated from four different cryogenic IgG3 mAb. Significantly, the sialic acid contents of the latter fraction became comparable to those of non-cryogenic IgG3 mAb. Finally, we observed that highly sialylated non-cryogenic IgG3 mAb was more potent in the inhibition of Cryoprecipitation of cryogenic IgG3 mAb. Our results thus suggest that the content of negatively charged sialic acids in oligosaccharide side chains is one of the critical factors to determine IgG3 cryoglobulin activity, along with amino acid sequences of the IgG3 variable regions.
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level of galactosylation determines cryoglobulin activity of murine igg3 monoclonal rheumatoid factor
Blood, 2002Co-Authors: Aki Kuroki, Yves D Pastore, Thierry Fulpius, Liliane Fossatijimack, Luc Reininger, Shuichi Kikuchi, Yasuhiro Kuroda, Frederic Lajaunias, Toho Toda, Munehiro NakataAbstract:Autoantibodies of the cryoprecipitating IgG3 isotype have been shown to play a significant role in the development of murine lupus-like autoimmune syndrome. At present, the structural basis of IgG3 Cryoprecipitation and its role in autoantibody pathogenicity remain to be defined. Using molecular variants of an IgG3 monoclonal rheumatoid factor, 6-19, derived from an autoimmune MRL-Fas(lpr) mouse, we have investigated the implication of charged residues in the heavy-chain variable (VH) region, potential CH3-linked oligosaccharides, and galactosylation of CH2-linked oligosaccharides in its cryoglobulin activity. The cryoglobulin activity of the IgG3 6-19 mutant bearing more negatively charged residues at VH 6 and 23 was found to be reduced but still highly significant, whereas that of the mutant lacking a potential CH3 glycosylation site remained unchanged. In marked contrast, IgG3 6-19 variants obtained from 6-19 heavy-chain transgenic mice displayed barely detectable cryoglobulin activity associated with an increased level of galactosylation in the CH2 oligosaccharide side chains. Thus, our data strongly suggest that the cryoglobulin activity of IgG3 6-19 autoantibody is critically determined by levels of galactosylation in the CH2 oligosaccharide side chains, whereas VH residues play a secondary role in 6-19 IgG3 cryoglobulin activity.
Bela Balint - One of the best experts on this subject based on the ideXlab platform.
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the use of single donor fibrin glue prepared by recycled Cryoprecipitation in experimental liver surgery
Haematologia, 2002Co-Authors: Bela Balint, Ibolja Cernak, Marijana Petakov, Diana Bugarski, Z Malicevic, Slavka Mandicradic, Jovan TaseskiAbstract:The purpose of the study was to evaluate the hemostatic effectiveness of fibrin glue (FG) prepared by a modification of Cryoprecipitation technique in experimental rat liver surgery. FG component 1 was prepared by triple or 'recycled' Cryoprecipitation method from single-donor plasma. Rats subjected to liver incision, partial and total lobectomy were treated with FG on the surgical cut surface or underwent standard surgical technique. The efficacy of FG-treatment was evaluated on the basis of the 24-hour survival ratio and peripheral blood hematological parameters. The mean values of fibrinogen, FXIII, fibronectin and horizontal tensile strength of FG were 54.2 ± 19.9 g/l, 13.5 ± 3.6 IU/ml, 3103.1 ± 148.9 mg/l, and 1.076 ± 0.18 N/cm2, respectively. The survival of FG-treated rats subjected to partial and total lobectomy was significantly higher in comparison to the FG-nontreated animals, accompanied with higher values of red blood cell counts, hemoglobin concentration and hematocrit. When liver incision was performed, although there were no differences in survival rate, FG-treated animals had significantly higher values of the tested hematological parameters. The presented results demonstrated that by using 'recycled' Cryoprecipitation it is possible to obtain high quality single-donor FG with successful hemostatic therapeutical effects, as confirmed in the experimental rat model of liver surgery.
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evaluation of fibrin glue prepared by recycled Cryoprecipitation in experimental liver surgery
Experimental Hematology, 2000Co-Authors: Bela Balint, Ibolja Cernak, Marijana Petakov, Diana Bugarski, Jovan Taseski, A Nesic, N StojanovicAbstract:Abstract Fibrin glue (FG) is a two component biologic system with adhesive, sealant and topical hemostatic properties, containing fibrinogen, factor XIII, fibronectin, thrombin, some antifibrinolytic agent and ionized calcium. The purpose of the study was to evaluate the hemostatic effectiveness of FG prepared by a modification of Cryoprecipitation technique in experimental rat liver surgery. FG component 1 was prepared by triple or "recycled" Cryoprecipitation method from single-donor plasma. Rats subjected to liver incision, partial and total lobectomy were treated with FG on the surgical cut surface or underwent standard surgical technique and the efficacy of the FG-treatment was evaluated on the basis of the 24-hour survival ratio and peripheral blood hematological parameters. The mean values of fibrinogen, FXIII, fibronectin and horizontal tensile strength of FG were 54.2 ± 19.9 g/l, 8.03 ± 2.3 IU/ml, 3103.1 ± 148.9 mg/l, and 1.076 ± 0.18 N/cm 2 , respectively. The survival of FG-treated rats subjected to partial and total lobectomy was significantly higher in comparison to the FG-nontreated animals, accompanied with higher values of red blood cell counts, hemoglobin concentration, as well as hematocrit. The survival of animals subjected to liver incision was not significantly different, however the differences in hematological parameters were significant in favor FG-treated animals. The presented results demonstrated that using "recycled" Cryoprecipitation it is possible to obtain high quality single-donor FG with successful hemostatic therapeutical effects, as confirmed in the experimental rat liver surgery.