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Biomedical subjects

B G Firkin

Publications and source records attributed to B G Firkin.

At least 73 records · Page 4Linked to original sources
PubMed1979

Altered erythrocyte pyrimidine activity in vitamin B12 or folate deficiency.

The net activity of orotidylic pyrophosphorylase and decarboxylase, sequential enzymes which catalyse the formation of uridine monophosphate from orotic acid in de novo pyrimidine biosynthesis, has been evaluated in erythrocytes of patients with folate or cobalamin deficiency. In patients with normoblastic haemopoiesis and normal cobalamin and folate status a direct relationship exists between the maturity of the peripheral blood erythrocyte population, as indicated by G6PD activity, and net orotidylic activity. In contrast in cobalamin or folate deficiency this co-ordinate relationship is not observed and net orotidylic activity is relatively reduced. Fractionation of erythrocytes by centrifugation demonstrates that this inordinately low orotidylic activity consistently occurs in the young erythrocyte population and is reversed by specific replacement therapy. In vitamin B12 or folate deficiency an impressive array of evidence now exists to implicate altered folate metabolism for the observed alterations in purine and pyrimidine metabolism (Das & Herbert, 1976). Of these changes the cornerstone defect resulting in megaloblastic maturation is impaired methylation of deoxyuridine monophosphate to thymidine monophosphate (Hoffbrand et al, 1976). In this context the reduced serum uridine plus uracil levels in patients with vitamin B12 deficiency (Parry & Blackmore, 1976) and the haematological response of these patients to orotic acid therapy (Rundles & Brewer, 1958) are not readily explicable. Since the conversion of orotic acid to uridine monophosphate depends on the integrity of the coupled activities of orotidylic pyrophosphorylase and decarboxylase, this study has quantitated this capacity in peripheral blood erythrocytes in patients with vitamin B12 or folate deficiency.

Erythrocytes↗
PubMed1978

Demonstration of a platelet bypass mechanism in the clotting system using an acquired anticoagulant.

A lupus-type anticoagulant which causes strong inhibition of the partial thromboplastin time with kaolin (PTTK), the stypven time, and the thrombin generation tests has been investigated. All tests for platelet function were normal, as were all specific coagulation factor assays with the exception of a slightly reduced factor XI in this patient. A diethylaminoethyl-cellulose-immunoglobulin (DEAE-cellulose-IgG) fractionation of the patient's plasma produced two peaks containing inhibitory activity in the PTTK test. The first of these peaks had a cloudy appearance, suggesting the presence of immunoglobulin aggregates. Studies with IgG aggregates prepared from normal IgG and from the patient's IgG demonstrated that such aggregates were not the cause of inhibition. It was possible to neutralize the inhibitory activity of the purified IgG but not platelet-poor plasma (PPP) with a rabbit anti-IgG. The inhibition of the patient's PPP in the thrombin generation, the contact product, and the stypven time tests were corrected by the inclusion in the test system of platelets activated either by aggregation due to adenosine diphosphate (ADP) or formalin fixation and washing. These studies lend support to earlier findings that platelets interact at several sites in the coagulation cascade.

Antibodies↗
PubMed1976

Chloramphenicol-a possible role in the treatment of leukaemia?

The effect of chloramphenicol in short term in-vitro bone marrow cultures was studied. There was a striking reduction in the incorporation of tritiated thymidine into DNA in bone marrow cultures with abnormal proliferative properties as compared with normal tissue. A 50% reduction in DNA thymidine incorporation in leukaemia marrow was also obtained with in-vitro chloramphenicol concentrations which in contrast had little or no effect in normal tissue. These in-vitro levels of the antibiotic can be readily achieved in vivo. An in-vivo study confirmed the ability of chloramphenicol to reduce the white cell and blast count in a patient with chronic myeloid leukaemia in blastic transformation.

Anemia, Hemolytic↗
PubMed1976

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↗
PubMed1976

Further studies of the interaction between ristocetin and fibrinogen.

Fibrinogen (FG) precipitation by ristocetin is enhanced by lowering the temperature to 4 degrees C. The precipitate has similar properties to an acquired cryofibrinogen being resolubilised on rewarming to 37 degrees C, and the process of precipitation and resolubilsation can be repeated indefinitely by lowering and raising the temperature. Other plasma proteins are also precipitated by ristocetin, but to a lesser degree than FG. This property appears to have no relation to ristocetin's ability to aggregate platelets in the presence of von Willebrand's factor, since platelet aggregation by ristocetin is inhibited by lowering the temperature.

Chemical Precipitation↗
PubMed1975

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↗