Biomedical subjects

Keith Gomez

Publications and source records attributed to Keith Gomez.

4 recordsLinked to original sources

PubMed2006

Tissue factor initiated blood coagulation.

Tissue factor (TF) is the cellular receptor and cofactor for blood coagulation factor (F) VII. Exposure of flowing blood to cells that express TF leads to the initiation of blood coagulation. Blood coagulation is tightly regulated to generate a local fibrin clot at the site of vascular injury without compromising blood flow in the vasculature. This chapter describes the initiation and propagation of the response and how it is ultimately down-regulated to prevent widespread inappropriate blood coagulation.

Animals↗

PubMed2005

Inhibition of coagulation by macromolecular complexes.

The role of vertebrate blood coagulation is to rapidly prevent the loss of body fluids following vascular injury without compromising blood flow through either the uninjured or damaged vessels. To achieve this the coagulation network is initiated and regulated by a complex network of interactions that are under the control of both positive and negative feedback loops that result in controlled fibrin deposition and platelet activation only at the site of injury. Anticoagulant molecules play key roles in preventing inappropriate initiation of coagulation as well as down-regulating thrombin generation at the site of injury. Tissue factor pathway inhibitor (TFPI) inhibits the initiation complex, antithrombin (AT) inhibits the active serine proteases directly, whereas the activated protein C pathway inhibits coagulation by inactivating the cofactors V and VIII. In this review the structure and function of these anticoagulant molecules and their inhibitory complexes is discussed.

Amino Acid Sequence↗

PubMed2004

Hunting for the mutation in inherited thrombophilia.

Mutation detection in inherited thrombophilia remains largely confined to the research laboratory. However, there are specific situations when investigating the genetic defect causing thrombophilia can provide additional useful clinical information. This review discusses the value of genetic analysis in the common inherited thrombophilias.

Antithrombins↗

PubMed2004

Two novel mutations in severe factor VII deficiency.

We have characterized the molecular defect in two families with severe factor VII (FVII) deficiency. In family I, the proband was found to be homozygous for a novel 18 bp deletion in exon 8 (g.10896-10913del) resulting in the in-frame deletion of six amino acids in the serine protease domain. Molecular modelling suggests the deletion is likely to disrupt folding of the FVII molecule. The reduced FVII antigen (21 U/dl) and negligible activity (0.4 U/dl) in the patient's plasma indicated that the deletion affected both the secretion/stability and function of the mutant protein. In family II, the proband was found to be a compound heterozygote for a novel missense mutation (g.7884G>A; FVII G117R) in exon 5 encoding the EGF2 domain of FVII and a nonsense mutation (g.8960C>T; FVII R152X) in exon 6. Extensive sequence comparison in a wide evolutionary context suggested that the Gly117 residue is critical for structure of FVII. The grossly reduced FVII antigen (1.1 U/dl) and activity (0.4 U/dl) plasma values indicate the mutation primarily affected the folding/secretion or stability of the protein.

Animals↗