Continuing objective is to transfer the specialized protein and enzyme chemical knowledge accumulated over the years in our laboratory on the factor XIII (fibrin stabilizing factor) and similarly acting transaminating enzyme systems, when transglutaminases become discharged from tissues into plasma, to complex pathological phenomena. Development of novel testing modalities based on biochemical understanding will aid in the early detecting of certain thrombotic tendencies, as well as in the diagnosis of hereditary and acquired bleeding disorders. Also, molecular studies of abnormal conditions in Nature provide unusual opportunities for validating and extending our knowledge into important regulatory aspects of the physiology of normal blood coagulation.
Specific aims are grouped under the following categories, each representing several different projects. 1. Maturation of factor XIII in the full-term and premature newborn. Is there a fetal form of factor XIII? 2. Molecular studies on hemorrhagic disorders of fibrin stabilization: (a) hereditary deficiencies; (b) target specificities of circulating inhibitors. 3. Novel testing modalities for factor XIII and for tissue transglutaminases, should the latter become discharge into plasma under pathological circumstances. Detection of circulating factor XIIIa activity as an indicator of thrombotic tendency. 4. Fibronectin as the carrier of tissue transglutaminase in plasma. Practical and fundamental considerations.
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