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T Girard

Publications and source records attributed to T Girard.

26 records · Page 2Linked to original sources

Tissue factor pathway inhibitor: the carboxy-terminus is required for optimal inhibition of factor Xa.

Tissue factor pathway inhibitor (TFPI) is a multivalent Kunitz-type protease inhibitor that binds to and inactivates factor Xa directly, and in a factor Xa-dependent fashion inhibits the factor VIIa/tissue factor catalytic complex. TFPI is a slow, tight-binding, competitive, and reversible inhibitor of factor Xa, in which the formation of an initial encounter complex between TFPI and factor Xa is followed by slow isomerization to a final, tightened complex. Wild-type recombinant TFPI (rTFPI), expressed in mouse C127 cells, separates into two forms on heparin-agarose chromatography that elute at 0.3 mol/L and 0.6 mol/L NaCl. Western blot analysis shows that both forms contain the N-terminus of full-length TFPI, but only rTFPI(0.6) is recognized by an antibody directed against the C-terminus. rTFPI(0.3) and rTFPI(0.6) inhibit factor Xa with 1:1 stoichiometry and inhibit factor VIIa/tissue factor equally in an endpoint-type assay. However, rTFPI(0.6) is a more potent inhibitor than rTFPI(0.3) of coagulation in normal plasma induced by either factor Xa or tissue factor. The initial inhibition of factor Xa (less than 5 seconds) produced by rTFPI(0.6) is several-fold greater than that produced by rTFPI(0.3), presumably reflecting a lower Ki of the immediate encounter complex between factor Xa and TFPI. The differential effect of these forms of TFPI on tissue factor-induced coagulation in normal plasma appears to be directly related to their ability to inhibit factor Xa. To confirm the role of the C-terminal region of TFPI in optimal factor Xa inhibition, a carboxy-terminal mutant of rTFPI, which is truncated after leucine 252 and thus lacks the basic sequence K T K R K R K K Q R V K (residues 254-265), was expressed in C127 cells. This form of rTFPI elutes from heparin-agarose at 0.28 mol/L NaCl and inhibits factor Xa at a rate that is slower than rTFPI(0.3). The Ki(final)s for factor Xa inhibition by rTFPI(0.6), rTFPI(0.3), and rTFPI1-252 are 3.1 +/- 0.6, 19.6 +/- 0.8, and 19.6 +/- 3.0 pmol/L, respectively.

Amino Acid Sequence↗

[Late results following shaft fractures of the lower extremities in the growth period].

In a retrospective study 275 femoral-shaft fractures and 652 tibial respectively fibular fractures of the growing skeleton were evaluated. A posttraumatic limb length difference was present in 70% after femoral fractures and in 40% following fractures of the lower leg. In the control group of 822 examined persons we found an idiopathic difference of the length of the limb in 25%. Following femoral fractures the limb length difference was in average 10 mm. However following fractures of the tibia and fibula it was 7 mm. There is no evidence that an established difference in length will improve in course of growth. Factors influencing the alteration of length are discussed. It could be shown that there is no primary therapeutic way of influencing the alteration of length and that the so called prophylactic "shortening" at time of consolidation cannot prevent future lengthening. Also we could prove that rotational deformities of the femur show a good prognosis regarding spontaneous correction. Deformities of the lower leg however do not show spontaneous correction and ought to be corrected primarily. The incidence and degree of future alteration of length of the lower limb can only be influenced indirectly by early definite stabilisation of the fracture without leaving an axial deformity behind. For stable non-dislocated fractures the plaster of cast treatment is sufficient. However for unstable, dislocated (displaced) fractures which need anaesthesia for primary treatment, the unilateral external fixator is proposed as the method of treatment. Functional follow up examinations to evaluate possible posttraumatic alteration of the length of the lower limb, have to be performed at least for two years after the accident.

Adolescent↗