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Biomedical subjects

C Ridler

Publications and source records attributed to C Ridler.

5 recordsLinked to original sources
PubMed2006

Permanent partial phenotypic correction and tolerance in a mouse model of hemophilia B by stem cell gene delivery of human factor IX.

Immune responses against an introduced transgenic protein are a potential risk in many gene replacement strategies to treat genetic disease. We have developed a gene delivery approach for hemophilia B based on lentiviral expression of human factor IX in purified hematopoietic stem cells. In both normal C57Bl/6J and hemophilic 129/Sv recipient mice, we observed the production of therapeutic levels of human factor IX, persisting for at least a year with tolerance to human factor IX antigen. Secondary and tertiary recipients also demonstrate long-term production of therapeutic levels of human factor IX and tolerance, even at very low levels of donor chimerism. Furthermore, in hemophilic mice, partial functional correction of treated mice and phenotypic rescue is achieved. These data show the potential of a stem cell approach to gene delivery to tolerize recipients to a secreted foreign transgenic protein and, with appropriate modification, may be of use in developing treatments for other genetic disorders.

Animals↗
PubMed1992

Handling of 5-hydroxytryptamine by platelets in migraine.

There is little dispute that a link exists between 5-hydroxytryptamine (5HT) and migraine but the exact mechanism of an attack has yet to be established. The handling of 5HT by the platelet is regarded as a simple model of the handling of 5HT by nerve terminals. If differences are seen in how the platelets from migraineurs handle 5HT compared to those from a control population, it is possible that a similar difference exists in the nerve terminal. The Haemostatometer allows the rapid and simultaneous in vitro assessment of platelet function (shear-induced haemostasis), coagulation and thrombolysis from non anticoagulated blood samples. In this study, a baseline comparison of haemostasis was made on 20 migraineurs between attacks and 20 controls. No differences were found in the results from each of the two groups. 5 microM of 5HT was then added to blood taken from 10 migraineurs and 10 controls and the recordings were repeated. Again, no differences were found between the results from the two groups. In blood taken from both migraineurs and controls, the effect of 5HT was to significantly enhance clotting time and clot lysis. No effect was seen on primary aggregation. The possible reasons for and significance of these findings is discussed.

Adult↗
PubMed1989

Haemostasis in migraine.

There has been much discussion about the role of platelets in the pathogenesis of migraine. A new in vitro technique using a custom built device called the Haemostatometer measures haemostasis, thrombolysis, and coagulation from non-anticoagulated, undiluted (native) blood. Using this device, data were analysed from blood samples taken from 10 migraineurs between attacks and 10 control subjects. Results showed no difference in haemostasis, spontaneous thrombolysis or coagulation between migraineurs and control subjects.

Adolescent↗
PubMed1985

Plasma or serum from patients with systemic sclerosis alters behaviour of normal erythrocytes.

Incubation of washed normal erythrocytes with fresh or frozen plasma or serum from patients with systemic sclerosis (SS) significantly decreased the filterability of the cells, whereas the incubation of homologous normal serum or plasma with washed erythrocytes did not alter the filterability of these cells. The endothelial cell adherence of normal erythrocytes was increased by 3.5- and 2.6-fold (p less than 0.01) respectively when plasma or serum from patients with SS rather than that from normal controls was added to the incubation medium. Further investigation and isolation of the reactive material(s) present in the serum and plasma of patients with SS, which affect the deformability and endothelial cell adherence of erythrocytes, may be helpful in understanding the pathogenesis of the disease.

Adult↗