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Biomedical subjects

J Koutts

Publications and source records attributed to J Koutts.

67 records · Page 4Linked to original sources

Active release of human platelet factor VIII-related antigen by adenosine diphosphate, collagen, and thrombin.

Platelet Factor VIII-related antigen (VIIIR:Ag) represents a significant proportion of the total circulating VIIIR:Ag pool. However, its participation in the events of primary hemostasis has not been shown. We now report that platelet-contained VIIIR:Ag is released from platelets by collagen, ADP and thrombin. The concentrations of these agonists, required for VIIIR:Ag release, are the same or lower than those required for release of serotonin, lysosomal enzymes, or fibrinogen. This release has the features of an energy-dependent secretory response because it is blocked by the metabolic inhibitors, antimycin A and 2-deoxy-D-glucose. The electrophoretic characteristics of the VIIIR:Ag released by collagen and ADP are similar to those of plasma VIIIR:Ag. However, thrombin-released platelet VIIIR:Ag differs from that of plasma in that the less anodal forms are relatively depleted. These differences do not appear to be the result of proteolytic degradation of platelet-derived VIIIR:Ag, but may reflect interactions between specific molecular forms of VIIIR:Ag and the platelet membrane. These studies suggest mechanisms by which platelet-contained VIIIR:Ag may contribute to the primary events of hemostasis.

Adenosine Diphosphate↗

Immunological evidence that human factor VIII is composed of two linked moieties.

The relationship between the three measurable components of the factor VIII complex, procoagulant activity (VIII:C), Ristocetin cofactor (VIIIR:WF) and factor VIII related antigen (VIIR:AG), has been investigated using a solid phase immunoadsorption system in which homologous antibodies specific for VIII:C are insolubilized onto Sepharose beads. The VIII:C component of partially purified factor VIII can be completely separated from the Willebrand factor (VIIIR:WF/VIIIR:AG) by this technique. The loss of VIII:C has no detectable effect on the molecular size, antigenicity or electrophoretic mobility of the original molecule. The Willebrand factor (WF) recovered from these immunoadsorption columns was used to absorb heterologous antisera to factor VIII. A specific heterologous antiserum to VIII:C, which no longer neutralized VIIIR:WF nor precipitated VIIIR:AG, was obtained. Heterologous antisera to WF were prepared which potently neutralized VIIR:WF and precipitated with VIIIR:AG, but also weakly neutralized VIII:C (titre I u/ml). This study is compatible with the theory that VIII:C and VIIIR:WF/VIIIR:AG are two different but linked entities.

Antibodies↗

Actions of ristocetin on platelets.

The absence of ristocetin-induced platelet aggregation appears to correlate with the platelet defect in von Willebrand's disease, suggesting that this reaction mimics a physiological process. The effect of ristocetin on plasma and on the residual levels of the von Willebrand factor (vWF), Factor VIII procoagulant activity, and Factor VIII-related protein in plasma after aggregation of platelet rich plasma by this agent has been studied in order to further elucidate the mechanism and requirements of this reaction. Ristocetin-induced platelet aggregation causes a consumption of vWF, Factor VIII procoagulant activity, and Factor VIII antigen from the supernatant plasma which is proportional to the number of platelets aggregated. Such a consumption of these factors does not appear to occur after aggregation by other agents. Factor VIII procoagulant activity does not appear necessary for ristocetin-induced platelet aggregation, yet is utilized in this process. These findings support the hypothesis that the molecule associated with Factor VIII procoagulant activity is carried by the molecule necessary for ristocetin-induced platelet aggregation.

Blood Platelets↗

Topical treatment of recurrent herpes simplex with cytosine arabinoside.

A double-blind controlled clinical trial of the topical use of cytosine arabinoside in recurrent herpes simplex of the face and genital region showed no significant difference in the efficiency of a placebo as compared with cytosine arabinoside. The high rate of placebo response (70%) found in this trial makes the assessment of any drug treatment for herpes simplex particularly difficult.

Administration, Topical↗

Heterogeneity in biological activity of human factor VIII antibodies.

Antibodies against factor VIII collected from six patients were studied for their effect on factor-VIII coagulant activity, Willebrand factor activity (WF) and factor-VIII-related antigen. The results demonstrate differences between individual antibodies; some acting primarily as anti factor VIII, others inhibiting both after VIII and WF. Differences in effect between plasma and serum indicate that the process of coagulation alters the interaction of these antibodies.

Factor VIII↗

A case of Hageman factor deficiency with myeloid leukaemia.

The co-existence of blastic transformation of chronic myeloid leukaemia and an isolated deficiency of coagulation factor XII (Hageman Factor), is reported. In the absence of any evidence of factor XII deficiency in the patient's siblings and children, it is uncertain if this represents an acquired factor XII deficiency due to myeloid leukaemia, or the coincidental occurrence of myeloid leukaemia with this autosomal recessive condition.

Blood Coagulation Disorders↗