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Biomedical subjects

M Mahmoud-Alexandroni

Publications and source records attributed to M Mahmoud-Alexandroni.

3 recordsLinked to original sources

Tissue and urokinase plasminogen activators in the environs of venous and ischaemic leg ulcers.

Urokinase plasminogen activator (uPA) and tissue plasminogen activator (tPA) were assayed in biopsies from the base, edge and adjacent skin of ischaemic and venous ulcers using a functional bioimmunoassay and a standard immunoassay. Two series of 14 biopsies were examined: from seven venous and seven ischaemic ulcers in the first series, eight venous and six ischaemic in the second. It was found that tPA was detected in only four samples of ulcer edge using the bioimmunoassay and in no sample by the standard immunoassay. By contrast, uPA was detected in all but one ulcer edge biopsy and at a significantly lower median concentration in the adjacent skin (16.9 units/g) than the ulcer edge (26.1 units/g) or base (32.3 units/g) (both P < 0.01). Levels of uPA were greater in the edge and base of venous compared with ischaemic ulcers. The predominant plasminogen activator in chronic leg ulcers is uPA; this activator may play an important role in wound healing.

Humans↗

Sensitive and direct assays for functionally active plasminogen activators (tissue-type and urokinase-type) in plasma.

A previously described bioimmunoassay for tissue-type plasminogen activator (t-PA) has been modified in terms of antibody concentration and conditions of incubation to achieve a sensitivity range of approximately 5-500 IU/L of t-PA. A similar assay has been developed for urinary-type plasminogen activator (U-PA), also known as urokinase (UK), achieving a sensitivity range of approximately 5-500 X 10(-1) IU/L. The direct sensitive t-PA assay has been demonstrated to be a quantitative alternative to the traditional semiquantitative euglobulin clot lysis time (ECLT) assay, with correlation coefficients of 0.967 and 0.914, depending on the laboratory where the ECLT was carried out. This assay has the added advantages of avoiding loss of t-PA or UK during the formation of the euglobulin fraction and of calibration in terms of International Standards for both t-PA and UK. With both these assays, it has been demonstrated that the enhanced fibrinolytic activity observed after exercise results from increased levels of t-PA while the level of UK in plasma remains unaltered. Free t-PA (10-60 IU/L) has been demonstrated in resting plasma, whereas the level of free UK activity was 50-100 IU/L. Venous occlusion of matched groups of subjects with and without deep venous thrombosis (DVT) showed a wide variation of response in t-PA levels in each group and no change in UK levels. There was no difference between the DVT and non-DVT groups, and this suggests that the notion of the "nonresponder" being more prone to thrombosis needs to be reexamined.

Adult↗

Roles for chloride ion and fibrinogen in the activation of [Glu1]plasminogen in human plasma.

Using two-dimensional immunoelectrophoresis and an antibody to alpha 2-antiplasmin, we assessed the plasmin generated in serum under different conditions as the plasmin-alpha 2-antiplasmin complex. Activation in serum of human [Glu1]plasminogen ([Glu1]Pg) by recombinant tissue plasminogen activator was inhibited by the normal serum levels of Cl- and was enhanced by physiological levels of fibrinogen in the presence or absence of Cl-. These results agree with the recognized ability of Cl- to induce a conformation in [Glu1]Pg less favorable for its activation than the conformation that results without Cl-. The enhancing effect of fibrinogen surpassed the inhibitory effect of Cl- over a wide range of recombinant tissue plasminogen activator concentrations in physiological serum. Lesser inhibition by Cl- was seen in a purified clot-lysis system, suggesting that [Glu1]Pg conformation when attached to soluble fibrin matrix was less affected by the anion. The data regarding the roles of circulating fibrinogen and Cl- in controlling the plasma level of activated [Glu1]Pg have important implications in thrombolytic therapy with recombinant tissue plasminogen activator.

Chlorides↗