Role of Cosolutes in the Aggregation Kinetics of Monoclonal Antibodies

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.

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Plasminogen Activation In Vivo upon Intravenous Infusion of DDAVP

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648390 ◽

1992 ◽

Vol 67 (01) ◽

pp. 111-116 ◽

Cited By ~ 64

Author(s):

Marcel Levi ◽

Jan Paul de Boer ◽

Dorina Roem ◽

Jan Wouter ten Cate ◽

C Erik Hack

Keyword(s):

Monoclonal Antibodies ◽

Plasminogen Activator ◽

Plasma Levels ◽

Fold Increase ◽

Fibrinolytic System ◽

Plasminogen Activation ◽

Plasminogen Activator Activity ◽

Insight Into

SummaryInfusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established.A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor α2 antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated α2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system.Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex.We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.

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Functional Fractionation of Platelets: Aggregation Kinetics and Glycoprotein Labeling of Differing Platelet Populations

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657259 ◽

1982 ◽

Vol 48 (02) ◽

pp. 211-216 ◽

Cited By ~ 12

Author(s):

V M Haver ◽

A R L Gear

Keyword(s):

Galactose Oxidase ◽

Aggregation Kinetics ◽

Maximal Rate ◽

Membrane Glycoproteins ◽

Whole Cells ◽

Reversible Aggregation ◽

Significant Difference ◽

Small Doses ◽

Major Loss ◽

Kinetics Of

SummaryPlatelet heterogeneity has been studied with a technique called functional fractionation which employs gentle centrifugation to yield subpopulations (“reactive” and “less-reactive” platelets) after exposure to small doses of aggregating agent. Aggregation kinetics of the different platelet populations were investigated by quenched-flow aggregometry. The large, “reactive” platelets were more sensitive to ADP (Ka = 1.74 μM) than the smaller “less-reactive” platelets (Ka = 4.08 μM). However, their maximal rate of aggregation (Vmax, % of platelets aggregating per sec) of 23.3 was significantly lower than the “less-reactive” platelets (Vmax = 34.7). The “reactive” platelets had a 2.2 fold higher level of cyclic AMP.Platelet glycoproteins were labeled using the neuraminidase-galactose oxidase – [H3]-NaBH4 technique. When platelets were labeled after reversible aggregation, the “reactive” platelets showed a two-fold decrease in labeling efficiency (versus control platelets). However, examination of whole cells or membrane preparations from reversibly aggregated platelets revealed no significant difference in Coomassie or PAS (Schiff) staining.These results suggest that the large, “reactive” platelets are more sensitive to ADP but are not hyperaggregable in a kinetic sense. Reversible aggregation may cause a re-orientation of membrane glycoproteins that is apparently not characterized by a major loss of glycoprotein material.

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Kinetics of vascular normalisation by VEGFR2 blockade governs brain tumour response to radiation: role of angiopoietin-1 and matrix metalloproteinases

Aktuelle Neurologie ◽

10.1055/s-2005-919261 ◽

2005 ◽

Vol 32 (S 4) ◽

Author(s):

F Winkler ◽

S Kozin ◽

R Tong ◽

D Hicklin ◽

L Munn ◽

...

Keyword(s):

Matrix Metalloproteinases ◽

Brain Tumour ◽

Tumour Response ◽

Kinetics Of ◽

Angiopoietin 1

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Role of biliary proteins and non-protein factors in kinetics of cholesterol crystallisation and gallstone growth

Frontiers in Bioscience ◽

10.2741/a705 ◽

2001 ◽

Vol 6 (4) ◽

pp. e154-167 ◽

Cited By ~ 5

Author(s):

Albert K Groen

Keyword(s):

Kinetics Of

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Thermodynamic and Kinetic Investigation of the Solvent Effect on the Oxidation of [Co(en)2SCH2COO]+ with S2O82- In Water-Methanol and Water-tert-Butyl Alcohol Mixtures

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19931001 ◽

1993 ◽

Vol 58 (5) ◽

pp. 1001-1006 ◽

Cited By ~ 1

Author(s):

Oľga Vollárová ◽

Ján Benko

Keyword(s):

Transfer Functions ◽

Activation Parameters ◽

Butyl Alcohol ◽

Oxidation Of Co ◽

Kinetics Of Oxidation ◽

Tert Butyl ◽

Tert Butyl Alcohol ◽

Alcohol Mixtures ◽

Kinetics Of

The kinetics of oxidation of [Co(en)2SCH2COO]+ with S2O82- was studied in water-methanol and water-tert-butyl alcohol mixtures. Changes in the reaction activation parameters ∆H≠ and ∆S≠ with varying concentration of the co-solvent depend on the kind of the latter, which points to a significant role of salvation effects. The solvation effect on the reaction is discussed based on a comparison of the transfer functions ∆Ht0, ∆St0 and ∆Gt0 for the initial and transition states with the changes in the activation parameters accompanying changes in the CO-solvent concentration. The transfer enthalpies of the reactant were obtained from calorimetric measurements.

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