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- Cheng, X F, et al.
(författare)
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Binding of tissue plasminogen activator to endothelial cells. The effect on functional properties. Localization of a ligand in the B-chain of tPA.
- 1995
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Ingår i: Thrombosis Research. - 0049-3848 .- 1879-2472. ; 77:2, s. 149-64
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Tidskriftsartikel (refereegranskat)abstract
- The binding of 125I-labelled tissue plasminogen activator (tPA), the tPA A- or B-chain to endothelial cells (EC) were studied in suspensions of cultured human umbilical vein EC (HUVEC) or immortalized microvascular EC (HMEC). By determinations of the concentration-dependent binding it was shown that both the A-chain and the B-chain, which were isolated after partial reduction of two-chain tPA, contain ligands for binding to EC. The affinity for the B-chain was much higher than for the A-chain according to Scatchard analysis (Kd 24 and 515 nM, respectively), whereas the number of binding sites was higher for the A-chain than for the B-chain (Bmax 8 x 10(5) and 1.2 x 10(5), respectively). There were no cross interactions between the A- and B-chains and their binding sites. The binding of tPA to EC induced an almost 100-fold increase of the activation rate when compared to the same amount of enzyme in free solution, which in contrast to the fibrin-induced stimulation was not inhibited by antibodies against fibrin. The enzymatic activity of the B-chain was much less affected by the association to the cells. Both tPA and the tPA B-chain were largely protected against inhibition by an excess plasminogen activator type-1 (PAI-1) when bound to EC, whereas the same amount of free tPA was totally inactivated. The competition studies strongly indicated that an N-terminal segment in the B-chain, AKHRRSPGER, may be the ligand part of the B-chain. It is interesting to note that this polypeptide segment also participates in a binding site for PAI-1, necessary for effective inhibition. This implies a possible competition between PAI-1 and a tPA-receptor for binding of tPA. High molecular weight urokinase had no quenching effect on the binding of the B-chain to EC.
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| 3. |
- Cvetkovic, Vladimir, et al.
(författare)
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Analysis of nonlinear effects on tracer migration in heterogeneous aquifers using Lagrangian travel time approach
- 1996
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Ingår i: Water resources research. - 0043-1397 .- 1944-7973. ; 32:6, s. 1671-1680
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Tidskriftsartikel (refereegranskat)abstract
- Advective transport in a heterogeneous two-dimensional aquifer is simulated and quantified by the statistical moments of tracer travel time and transverse displacement. These moments depend on the statistics of the Lagrangian velocity given as a function of space rather than time. A comparison is made with first-order results that appear to be robust for log transmissivity variance at least up to 1. Lagrangian statistics for travel time clearly expose a few essential features of nonlinear transport: nonstationary distribution and the increasing integral scale of the Lagrangian velocity. These reflect the tendency of streamlines to concentrate into relatively few flow paths ('preferential flow') for increasing log transmissivity variance. Two simple empirical relationships are identified that in combination with first-order results for the flow capture the main features of nonlinear transport. The proposed methodology can readily be generalized for analyzing advective transport under more complex flow conditions and for establishing relatively simple analytical models for estimating solute mass flux in heterogeneous aquifers.
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