Biomedical subjects

N Carrell

Publications and source records attributed to N Carrell.

3 recordsLinked to original sources

PubMed1983

Hereditary dysfibrinogenemia in a patient with thrombotic disease.

A new case of congenital dysfibrinogenemia, in which the patient has severe thrombotic disease, is reported. The abnormal fibrinogen molecules are characterized by normal fibrinopeptide release with thrombin and defective polymerization in the formation of fibrin. Clotting times with ancrod and reptilase are significantly prolonged. All other coagulation tests (except those for fibrinogen function) are normal, and the patient has no other underlying disease. The apparent paradox of defective fibrinogen, which clots abnormally and is yet associated with thrombotic disease, can be explained by further analysis of the patient's fibrinogen. The two important functional properties of this fibrinogen are: (1) it forms fibrin gels that are extremely rigid, and (2) the fibrin is highly resistant to lysis by plasmin. Thus, although the abnormal fibrinogen forms defective clots, the fibrin that is formed cannot be removed by the fibrinolytic system. These results provide a molecular explanation for the thrombotic disease in this patient. This abnormal fibrinogen appears to have unique characteristics and has been designated as fibrinogen Chapel Hill Ill.

Adolescent↗

PubMed1982

Fibrinogen Chapel Hill II: defective in reactions with thrombin, factor XIIIa and plasmin.

Fibrinogen Chapel Hill II is a hereditary, abnormal fibrinogen which is characterized by poor substrate reactivity toward thrombin, factor XIIIa and plasmin. The patient has a low plasma level of clottable protein with normal antigen concentration, high amounts of fibrinogen related material in serum, and prolonged thrombin and reptilase clotting times. Fibrinopeptide release was decreased with both thrombin and ancrod, indicating that release of fibrinopeptide A from the abnormal fibrinogen was impaired. Sequence analysis indicated that the A peptide was normal. Light scattering indicated that the fibrils formed by thrombin were unusually short and thick. When clotted under crosslinking conditions gamma dimers formed normally but alpha polymer formation was defective. Under conditions which yielded complete plasmin digestion of normal fibrinogen only half of the patient fibrinogen was degraded beyond the fragment X stage. The rate of fibrinopeptide release from patient fragment X and NH2-terminal disulphide knot (N-DSK) was similar to that from the fibrinogen, indicating that the defect was contained within the N-DSK. A simple amino acid substitution could result in a conformational defect in the N-DSK sufficient to perturb the reactions involving thrombin, factor XIIIa and plasmin and also polymerization.

Biopolymers↗

PubMed1981

Fibronectin molecule visualized in electron microscopy: a long, thin, flexible strand.

We have determined the structure of plasma fibronectin by electron microscopy of shadowed specimens. the 440,000 molecular weight, dimeric molecule appears to be a long, thin, highly flexible strand. The contour length of the most extended molecules is 160 nm, but a distribution of lengths down to 120 nm was observed, indicating flexibility in extension as well as in bending. The average diameter of the strand is 2 nm and there are no large globular domains. the large fragments produced by limited digestion with plasmin are not globular domains but are segments of the strand, whose length corresponds to the molecular weight of the polypeptide chain. We conclude that each polypeptide chain of the dimeric molecule spans half the length of the strand, with their carboxyl termini joined at the center of the strand and their amino termini at the ends. This model is supported by images of fibronectin-fibrinogen complexes, in which the fibrinogen is always attached to an end of the fibronectin strand.

Binding Sites↗