Causal modeling and alternative medicine.

Many problems of health promotion or prevention call for an understanding of relations among variables embedded in complex causal webs that may include psychosocial, cultural, or environmental factors as well as biological dysfunction. Experimental investigation of these kinds of research problems is frequently impossible or not feasible. Causal modeling, particularly latent variable structural modeling, can provide a useful alternative to manipulative experimentation when one is trying to build and test explanatory models in a rigorous and systematic fashion.

Interactions of plasma kallikrein and C1-s with normal and dysfunctional C1(-)-inhibitor proteins from patients with hereditary angioneurotic edema: analytic gel studies.

Purified preparations of normal C1(-)-inhibitor (C1(-)-INH) formed high mol wt complexes with plasma kallikrein that were stable during sodium dodecyl sulfate (SDS)-gel electrophoresis, but most of the dysfunctional C1(-)-INH proteins isolated from plasma of patients with type II hereditary angioneurotic edema (HANE) did not. Two of eight dysfunctional C1(-)-INH proteins were cleaved to lower mol wt forms that were not seen following the reaction of normal C1(-)-INH with equimolar amounts, or less, of plasma kallikrein. Only the higher mol wt component of normal C1(-)-INH (106,000 mol wt) appeared to form a stable complex with the plasma kallikrein, whereas both the 106,000 and 96,000 mol wt forms made stable complexes with C1-s.

Variability in purified dysfunctional C1(-)-inhibitor proteins from patients with hereditary angioneurotic edema. Functional and analytical gel studies.

C1(-)-inhibitor (C1(-)-INH) proteins from normal persons and members of eight different kindred with dysfunctional C1(-)-INH proteins associated with hereditary angioneurotic edema (HANE) were compared with respect to their inhibitory activity against purified preparations of C1s-, plasma kallikrein, activated forms of Hageman factor, and plasmin. Each dysfunctional C1(-)-INH protein showed a unique spectrum of inhibitory activity against these enzymes. Although none of the dysfunctional C1(-)-INH proteins significantly impaired amidolysis by plasmin, all but one inhibited activated Hageman factor.

The anticoagulant activity of dermatan sulphates: evidence against the involvement of antithrombin III.

Anticoagulant activity of dermatan sulphates is unaffected by antiserum specific for antithrombin III (AT III) unless the glycosaminoglycan preparation contains demonstrable heparin. 2 Only dermatan sulphate preparations of considerable heparin content potentiate AT III inhibition of thrombin, factor Xa and plasmin. 3 These data suggest that dermatan sulphates exert anticoagulant activity which, unlike that of heparin, is largely or totally independent of AT III.

Anticoagulant effects of sulphated polysaccharides in normal and antithrombin III-deficient plasmas.

1 Comparison of the effects of sulphated polysaccharides on thrombin-induced clotting of normal and antithrombin III-deficient plasmas suggests the involvement of antithrombin III (AT III) in the anticoagulant activities of cellulose, dextran and xylan sulphates. 2 AT III appears to play little or no role in the anticoagulant activity of carrageenans.

Evidence for antithrombin III involvement in the anticoagulant activity of cellulose sulphate.

1 Cellulose sulphate, like heparin, prolonged the clotting time in partial thromboplastin time (PTT) assays, inhibited the amidolytic activity of thrombin, was without effect on amidolysis catalysed by activated coagulation factor X(Xa), and potentiated the inhibition of both thrombin and Xa by antithrombin III (AT). 2 The anticoagulant activity of cellulose sulphate in PTT assays was, like that of heparin and heparin sulphate, but unlike that of dermatan sulphate, reduced by prior incubation of plasma with antiserum specific for AT. 3 These results, which suggest that the anticoagulant activity of cellulose sulphate is at least partially mediated through AT, are discussed in terms of the structural features of polysaccharides required for AT activation.