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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
1995-6-2
|
| pubmed:abstractText |
An antithrombin (AT) variant Ala382 to Thr (AT-TRI) was identified by mass spectrometric techniques. The variant behaved as a substrate rather than a thrombin inhibitor, but, contrary to previously described P12 AT variants, AT-TRI, expressed as a heterozygous dominant trait, caused severe thromboembolic tendency beginning in their teens in affected members of an English family. In addition, it underwent the S-to-R conformational state transition as evidenced by an increased resistance to thermal denaturation on active centre cleavage, but did not react with a monoclonal antibody, 4C9, directed against a neoepitope that is present on complexed and cleaved normal AT. Antithrombin-TRI, in plasma, was also associated with an abnormal high molecular weight (M(r)) 194,000) component composed of non-covalently-linked antithrombin molecules. This component (D194) showed low affinity for heparin and was devoid of antithrombin progressive activity. D194, isolated by ammonium sulphate precipitation and three chromatographic steps (heparin Sepharose, ion exchange and immunoaffinity), migrated as a single band of M(r) 60,000 on SDS-PAGE under both reducing and non-reducing conditions and was recognized by monospecific anti-human antithrombin antibodies, but did not immunoreact with antibodies raised against a number of proteins including albumin and thrombin. The above data and the fact that the 15 N-terminal amino acids of this M(r) 60,000 band were identical to that of normal antithrombin indicated that the inactive D194 component was composed of aggregated antithrombin molecules, possibly antithrombin trimers. In conclusion, early adulthood severe thromboembolic tendency, failure to expose the 4C9 epitope, and presence of aggregated AT molecules in the plasma are characteristic features of AT-TRI not previously described in other ALA-382 THR mutations.
|
| pubmed:grant | |
| pubmed:commentsCorrections | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Mar
|
| pubmed:issn |
0007-1048
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
89
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
589-601
|
| pubmed:dateRevised |
2009-9-29
|
| pubmed:meshHeading |
pubmed-meshheading:7734359-Adolescent,
pubmed-meshheading:7734359-Adult,
pubmed-meshheading:7734359-Amino Acid Sequence,
pubmed-meshheading:7734359-Antibodies, Monoclonal,
pubmed-meshheading:7734359-Antithrombins,
pubmed-meshheading:7734359-Blotting, Western,
pubmed-meshheading:7734359-Cyanogen Bromide,
pubmed-meshheading:7734359-Disease Susceptibility,
pubmed-meshheading:7734359-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:7734359-Female,
pubmed-meshheading:7734359-Hot Temperature,
pubmed-meshheading:7734359-Humans,
pubmed-meshheading:7734359-Mass Spectrometry,
pubmed-meshheading:7734359-Middle Aged,
pubmed-meshheading:7734359-Molecular Sequence Data,
pubmed-meshheading:7734359-Molecular Weight,
pubmed-meshheading:7734359-Point Mutation,
pubmed-meshheading:7734359-Protein Denaturation,
pubmed-meshheading:7734359-Thrombosis
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
Antithrombin-TRI (Ala382 to Thr) causing severe thromboembolic tendency undergoes the S-to-R transition and is associated with a plasma-inactive high-molecular-weight complex of aggregated antithrombin.
|
| pubmed:affiliation |
Thrombosis Research Institute, London.
|
| pubmed:publicationType |
Journal Article,
Case Reports,
Research Support, Non-U.S. Gov't
|