Biomedical subjects

A Cruikshank

Publications and source records attributed to A Cruikshank.

3 recordsLinked to original sources

PubMed2001

Role of zymogen and activated factor X as scaffolds for the inhibition of the blood coagulation factor VIIa-tissue factor complex by recombinant nematode anticoagulant protein c2.

Recombinant nematode anticoagulant protein c2 (rNAPc2) is a potent, factor Xa (fXa)-dependent small protein inhibitor of factor VIIa-tissue factor (fVIIa.TF), which binds to a site on fXa that is distinct from the catalytic center (exo-site). In the present study, the role of other fX derivatives in presenting rNAPc2 to fVIIa.TF is investigated. Catalytically active and active site blocked fXa, as well as a plasma-derived and an activation-resistant mutant of zymogen fX bound to rNAPc2 with comparable affinities (K(D) = 1-10 nm), and similarly supported the inhibition of fVIIa.TF (K(i)* = approximately 10 pm). The roles of phospholipid membrane composition in the inhibition of fVIIa.TF by rNAPc2 were investigated using TF that was either detergent-solubilized (TF(S)), or reconstituted into membranes, containing phosphatidylcholine (TF(PC)) or a mixture of phosphatidylcholine and phosphatidylserine (TF(PCPS)). In the absence of the fX derivative, inhibition of fVIIa.TF was similar for all three conditions (K(i) approximately 1 microm), whereas the addition of the fX derivative increased the respective inhibition by 35-, 150-, or 100,000-fold for TF(S), TF(PC), and TF(PCPS). The removal of the gamma-carboxyglutamic acid-containing domain from the fX derivative did not affect the binding to rNAPc2, but abolished the effect of factor Xa as a scaffold for the inhibition of fVIIa.TF by rNAPc2. The overall anticoagulant potency of rNAPc2, therefore, results from a coordinated recognition of an exo-site on fX/fXa and of the active site of fVIIa, both of which are properly positioned in the ternary fVIIa.TF.fX(a) complex assembled on an appropriate phospholipid surface.

Animals↗

PubMed1996

The rising prevalence of HIV-1 infection in patients attending an inner city accident and emergency department.

The recently published findings of the unlinked anonymous HIV prevalence study in England and Wales showed unchanging HIV prevalence in groups such as homo/bisexual men, and declining rates in non-injecting heterosexual men attending genitourinary medicine clinics. However, this multicentre study did detect a significant rise in seroprevalence rates in pregnant women in England and Wales and sentinel groups within hospitals in London, warning that changing patterns of HIV infection might account for these variable results. In 1992-1993 a seroprevalence study of adult patients attending the accident and emergency department at St. Mary's Hospital in West Central London showed a rate of HIV-1 infection of 1 in 77. We have repeated the seroprevalence study over the same calendar months in 1994-1995 to gain further information about HIV positive patients attending the department and to see whether a change in the patterns of HIV infection in the population served by St Mary's Hospital had occurred.

Adult↗

PubMedDate not supplied

Mutation and selection in a large population.

In this paper we study a large, but finite population, in which mutation and selection occur at a single genetic locus in a diploid organism. We provide theoretical results for the equilibrium allele frequencies, their variances and covariances and their equilibrium distribution, when the population size is larger than the reciprocal of the mean allelic mutation rate. We are also able to infer that the equilibrium distribution of allele frequencies takes the form of a constrained multivariate Gaussian distribution. Our results provide a rapid way of obtaining useful information in the case of complex mutation and selection schemes when the population size is large. We present numerical simulations to test the applicability of our theoretical formulations. The results of these simulations are in very reasonable agreement with the theoretical predictions.

Alleles↗