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Biomedical subjects

B McLeod

Publications and source records attributed to B McLeod.

29 records · Page 2Linked to original sources

Activation of complement by blood transfusion filters.

Fresh blood, stored blood and granulocyte concentrates were passed through 170-micron and microaggregate blood filters to determine the degree of complement activation that occurs during transfusion of citrated blood products. Complement activation was assessed by measurement of C3 conversion using crossed immunoelectrophoresis and by assessment of C5a using a leukocyte aggregation functional assay. Prefiltration, fresh or stored blood products showed 0-1% C3 activation. Postfiltration, the degree of C3 conversion did not change for fresh blood or granulocyte concentrates. For stored whole blood, the degree of C3 conversion increased slightly to 2-3%. Prefiltration results for all samples showed a low level of C5a which did not change after passage through any filter. Serum incubated with filter material at 37 degrees C showed 2-10% C3 conversion. In contrast, results with citrated plasma showed less than 3% conversion of C3. We conclude that although some filter materials may activate complement in serum, filtration of citrated blood products through microaggregate blood filters induces little complement activation.

Blood Transfusion↗

Accelerated prostacyclin degradation in the thrombotic thrombocytopenic purpura.

Plasma prostacyclin (PGI2) degradation rate was measured in a 39-year-old man with chronic thrombotic thrombocytopenic purpura (TTP). His disease responded to plasma exchange, or plasma infusion alone, given at 3-4 week intervals. Plasmapheresis with albumin replacement had an adverse effect. PGI2 degradation rate was measured by incubation of exogenous PGI2 with plasma at 37 degrees C and recording of PGI2 activity after one, five, and fifteen min incubation by measurement of inhibition of platelet aggregation. The PGI2 degradation rate of the patient was significantly higher than that of normal subjects. The degradation rate improved after each plasma treatment and correlated well with clinical improvement. Moreover, the degradation rate of PGI2 could be corrected in vitro by the addition of normal plasma. When the patients plasma was incubated with aortic rings, PGI2 activity was reduced but the level of its inactive end product, 6-keto-PGF1 alpha, was normal. These findings indicate that our patient had normal PGI2 stimulating activity but had an abnormal rate of PGI2 degradation. Accelerated PGI2 degradation which leads to PGI2 deficiency may be important in the pathogenesis of microvascular thrombosis.

Adult↗

Therapeutic plasmapheresis in systemic lupus erythematosus. Effect on immune complexes and antibodies to DNA.

The effect of plasmapheresis in 8 patients with systemic lupus erythematosus (SLE) was investigated. Drug treatment was maintained at a constant level for at least 4 weeks before plasmapheresis. Levels of immune complexes were measured by a Raji cell radioimmunoassay, and by a solid-phase C1q-binding assay. Antibodies to ds-DNA and ss-DNA were measured by the Farr assay. In all cases, immune complexes and antibodies were lowered by plasmapheresis. In 5 patients, plasmapheresis was followed by a rapid rebound of complexes and antibody to pretreatment levels. In 3 in whom plasmapheresis was followed by treatment with cyclophosphamide for 1 month, a sustained immunochemical and clinical improvement followed, lasting in 2 cases for up to 3 years.

Adolescent↗

Studies on the inhibition of C56-initiated lysis (reactive lysis). III. Characterization of the inhibitory activity C567-INH and its mode of action.

An activity in serum which inhibits reactive lysis has recently been shown to do so by preventing the attachment of C567 complexes to cells, and hence has been designated C567-INH. This report describes certain physiochemical characteristics of the inhibitory activity. It behaves as a heat-stable pseudoglobulin, soluble in 20 per cent Na2SO4, and having alpha1 mobility on Pevikon block electrophoresis. It is excluded from CM cellulose at pH 6-0, RSC Equals 0.007 M, is retained by an XM-100 membrane and is heterogenous on Sephadex G-200, eluting in at least two peaks. The combined active materials from the Sephadex column elute from DE-52 in at least four peaks. The mechanism of action of material from each of these four peaks is shown to involve prevention of attachment of C567 complexes to membranes, and this is shown to involve an effect on C567 complexes in solution rather than an effect on the membrane. A less dramatic effect on the lysis of EC567 by limited quanities of C8 and C9 can be demonstrated. Haemolytic studies using cell-bound C567 suggest that the interaction of C567-INH with C567 involves a loose reversible association. It is therefore postulated that C567-INH inhibits reactive lysis primarily by reversibly associating with the nascent C567 complex in solution, increasing its bulk and decreasing its diffusion capacity so that it is unable to reach a cell membrane before its haemolytic potential decays.

Animals↗

Studies on the inhibition of C56-initiated lysis (reactive lysis). V. The roleof C567-INH in the regulation of complement-dependent haemolysis initiated by cobravenom factor.

Activation of the alternative pathway of complement by a factor from cobra venom (CVF) can lead to lysis of unsensitized erythrocytes (E) of some species. In these studies we observed that alterations in CVF-induced lysis could be produced by manipulation of C567-INH, a naturally occurring inhibitory activity which acts on fluid phase C567 complexes. Venom lysis of sheep and guinea-pig E was markedly inhibited by serum fractions having C567-INH activity. Microgram quantities of poly-L-lysine (PLL), molecular weight 180,000, a polycation which is a functional antagonist to C567-INH in serum, potentiated CVF lysis of sheep and guinea-pig E, and permitted the lysis of human E, which are otherwise not suscepticle to CVF lysis. The potentiation of venom lysis by PLL seemed not to be due to alterations in the target cell membrane; furthermore, it in turn was reversed by substances with C567-INH activity. This suggests that the generation of fluid phase C567 complexes contributes to the CVF-induced lysis of erythrocytes of these species, and that the haemolytic potential of fluid phase C567 generated during alternative pathway activation by this means is regulated by C567-INH.

Ammonium Sulfate↗

Studies of the inhibition of C56-initiated lysis (reactive lysis). IV. Antagonism of the inhibitory activity c567-INH by poly-L-lysine.

The stable intermediate complex C56 can initiate the lysis (reactive lysis) of unsensitized erythrocytes (E) by the membrane attack machanism of complement. Certain serum constituents designated C567-INH inhibit reactive lysis by preventing the C567 complex, once formed, from attaching to a membrane surface. It is shown here that microgram quantities of poly-L-lysine (PLL), a synthetic polycation of molecular weight 180,000, can reverse the effests of C567-INH, and thereby potentiate formation of EC567 by erythrocytes, C56 and C7 in whole serum. Erythrocytes exposed to PLL in a preincubation step did not show either increased susceptibility to C567 or resistance to C567-INH, and reversal of C567-IHN by given amounts of PLL was not diminished as cell concentrations were greatly increased, indicating that the effect of PLL was predominantly directed against fluid phase rather than against erythrocyte membrane substrates. The effects of PLL and C567-INH were quantitatively reciprocal. Thus, PLL-induced potentiation of C56-induced lysis is a solute effect which seems to involve direct neutralization of naturally occurring serum inhibitors of the C567 trimolecular complex of complement. The use of PLL thus provides a suitable antagonist for C567-INH in reaction mixtures, and allows evaluation of the role of C567 and C567-INH in a variety of situations involving C-mediated lysis.

Alpha-Globulins↗

Guidelines for the use of imaging techniques for the investigation of venous thromboembolic disease.

The diagnosis of venous thromboembolic disease remains a difficult challenge. Chest radiography, ventilation/perfusion lung scanning, noninvasive leg testing, and pulmonary angiography were evaluated with regard to sensitivity, specificity, positive and negative predictive values. The need for treatment, observation, or serial testing with respect to risks and benefits of treatment and likelihood of serious outcomes was evaluated. The evidence for conclusions was based on the methodology and values of the Canadian Task Force on the Periodic Health Examination. The Diagnostic Imaging Advisory Group of the Canadian Association of Emergency Physicians developed eight recommendations.

Diagnostic Imaging↗

Diabetes educators international: third time lucky?

Three attempts have been made to establish an international diabetes educators network (1984, 1988, 1991). This paper outlines the early meetings, and reports on the most recent 1991 initiative and the recommendations of three education workshops held during the International Diabetes Federation Congress (IDF) in Washington, DC, 1991. As a result of the workshops, a Steering Committee was formed to determine a structure and funding for an international diabetes educators network, to foster international networking, to establish communication with the IDF, and to plan another workshop during the 15th IDF Congress in Kobe, Japan.

Diabetes Mellitus↗