scholarly journals Cooperative activation of human factor IX by the human extrinsic pathway of blood coagulation

1991 ◽  
Vol 266 (17) ◽  
pp. 11317-11327 ◽  
Author(s):  
J.H. Lawson ◽  
K.G. Mann
Keyword(s):  
Blood Coagulation ◽  
Human Factor ◽  
Factor Ix ◽  
Extrinsic Pathway ◽  
Human Factor Ix ◽  
Cooperative Activation

Myocardial fibrosis in mice with overexpression of human blood coagulation factor IX

Blood ◽  
2003 ◽  
Vol 101 (5) ◽  
pp. 1871-1873 ◽  
Author(s):  
Afshin Ameri ◽  
Sumiko Kurachi ◽  
Katsuo Sueishi ◽  
Mitsuhiro Kuwahara ◽  
Kotoku Kurachi
Keyword(s):  
Risk Factor ◽  
Blood Coagulation ◽  
Myocardial Fibrosis ◽  
Human Factor ◽  
Coagulation Factor ◽  
Left Ventricular ◽  
Factor Ix ◽  
Left Ventricular Myocardium ◽  
Direct Demonstration ◽  
Human Factor Ix

Elevated circulatory levels of many blood coagulation factors are known to be a risk factor for deep vein thrombosis in humans. Here we report the first direct demonstration of a close association between elevated circulatory factor IX levels in mice with thrombosis as well as myocardial fibrosis. Transgenic mice overexpressing human factor IX at persistently high levels died at much younger ages than their cohorts expressing lower levels, or nontransgenic control animals. The median survival age of animals was inversely related to the circulatory levels of human factor IX. Prematurely dying animals had focal fibrotic lesions predominantly present in the left ventricular myocardium, and vasculatures in these lesions showed fibrin deposition. Thromboemboli were also present in other organs, including lung and brain. These observations support the hypothesis that persistently high circulatory levels of factor IX are a risk factor not only for thrombosis and/or thromboembolism, but also for myocardial fibrosis mimicking human myocardial infarction.

scholarly journals Expression and characterization of human factor IX. Factor IXthr-397 and factor IXval-397

1991 ◽  
Vol 266 (23) ◽  
pp. 15213-15220
Author(s):  
N. Hamaguchi ◽  
P.S. Charifson ◽  
L.G. Pedersen ◽  
G.D. Brayer ◽  
K.J. Smith ◽  
...  
Keyword(s):  
Human Factor ◽  
Factor Ix ◽  
Human Factor Ix

scholarly journals Tyrosine 69 of the first epidermal growth factor-like domain of human factor IX is essential for clotting activity.

1993 ◽  
Vol 268 (24) ◽  
pp. 17727-17733
Author(s):  
P.E. Hughes ◽  
G. Morgan ◽  
E.K. Rooney ◽  
G.G. Brownlee ◽  
P. Handford
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Human Factor ◽  
Factor Ix ◽  
Human Factor Ix ◽  
Epidermal Growth

scholarly journals The binding of human factor IX to endothelial cells is mediated by residues 3-11.

1992 ◽  
Vol 267 (29) ◽  
pp. 20529-20531
Author(s):  
W.F. Cheung ◽  
N Hamaguchi ◽  
K.J. Smith ◽  
D.W. Stafford
Keyword(s):  
Endothelial Cells ◽  
Human Factor ◽  
Factor Ix ◽  
Human Factor Ix

scholarly journals The three-dimensional structure of the first EGF-like module of human factor IX: Comparison with EGF and TGF-α

1992 ◽  
Vol 1 (1) ◽  
pp. 81-90 ◽  
Author(s):  
M. Baron ◽  
D.G. Norman ◽  
T.S. Harvey ◽  
I.D. Campbell ◽  
P.A. Handford ◽  
...  
Keyword(s):  
Human Factor ◽  
Three Dimensional ◽  
Factor Ix ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Human Factor Ix

scholarly journals Electroimmunoassay of Factor IX in the Detection of Haemophilia B Carriers

1977 ◽  
Author(s):  
F. Panicucci ◽  
U. Baicchi ◽  
A. Sagripanti ◽  
E. Pinori
Keyword(s):  
Genetic Variants ◽  
Human Factor ◽  
Factor Ix ◽  
Agarose Gel ◽  
Haemophilia B ◽  
Method Factor ◽  
Human Factor Ix ◽  
Monospecific Antiserum ◽  
Normal Women ◽  
Almost All

Parallel determinations of factor IX activity and factor IX antigen were carried out on 28 haemophilia B carriers and on 20 normal women. Factor IX activity was measured by a one stage method. Factor IX antigen was quantified by electroimmuno assay in agarose gel containing heterologous monospecific antiserum against human factor IX.The activity was observed to be at the same level as the antigen in normal women. Discrepancy was not found between the antigen and the activity in almost all of carriers: only in the mothers of haemophiliacs Bor B+ or BM the factor IX antigen resulted greater than that activity. Our results show that electroimmuno-assay may be used to study carriers of haemophilia B genetic variants and confirm that in the majority of cases they can probably be diagnosed on the basis of factor IX activity alone.

scholarly journals Production of human factor IX in animals by genetically modified skin fibroblasts: potential therapy for hemophilia B

Blood ◽  
1989 ◽  
Vol 73 (2) ◽  
pp. 438-445
Author(s):  
TD Palmer ◽  
AR Thompson ◽  
AD Miller
Keyword(s):  
Human Factor ◽  
Normal Skin ◽  
Human Fibroblasts ◽  
Retroviral Vectors ◽  
Factor Ix ◽  
Skin Fibroblasts ◽  
Hemophilia B ◽  
Clotting Factor ◽  
Human Factor Ix

Inherited diseases might be treated by introducing normal genes into a patient's somatic tissues to correct the genetic defects. In the case of hemophilia resulting from a missing clotting factor, the required gene could be introduced into any cell as long as active factor reached the circulation. We previously showed that retroviral vectors can efficiently transfer genes into normal skin fibroblasts and that the infected cells can produce high levels of a therapeutic product in vitro. In the current study, we examined the ability of skin fibroblasts to secrete active clotting factor after infection with different retroviral vectors encoding human clotting factor IX. Normal human fibroblasts infected with one vector secreted greater than 3 micrograms factor IX/10(6) cells/24 h. Of this protein, greater than 70% was structurally and functionally indistinguishable from human factor IX derived from normal plasma. This suggests that infected autologous fibroblasts might provide therapeutic levels of factor IX if transplanted into patients suffering from hemophilia B. By transplanting normal diploid fibroblasts infected with the factor IX vectors, we showed that human factor IX can be produced and is circulated at readily detectable levels in rats and mice.

scholarly journals Proteolytic inactivation of blood coagulation factor IX by thrombin

Blood ◽  
1985 ◽  
Vol 66 (6) ◽  
pp. 1302-1308 ◽  
Author(s):  
W Kisiel ◽  
KJ Smith ◽  
BA McMullen
Keyword(s):  
Human Factor ◽  
Coagulation Factor ◽  
Factor Ix ◽  
Light Chains ◽  
Factor X ◽  
Amino Terminal ◽  
Coagulation Factor Ix ◽  
Human Factor Ix ◽  
Coagulant Activity

Coagulation factor IX is a vitamin K-dependent glycoprotein that circulates in blood as a precursor of a serine protease. Incubation of human factor IX with human alpha-thrombin resulted in a time and enzyme concentration-dependent cleavage of factor IX yielding a molecule composed of a heavy chain (mol wt 50,000) and a doublet light chain (mol wt 10,000). The proteolysis of factor IX by thrombin was significantly inhibited by physiological levels of calcium ions. Under nondenaturing conditions, the heavy and light chains of thrombin- cleaved factor IX remained strongly associated, but these chains were readily separated by gel filtration in the presence of denaturants. Amino-terminal sequence analyses of the isolated heavy and light chains of thrombin-cleaved human factor IX indicated that thrombin cleaved peptide bonds at Arg327-Val328 and Arg338-Ser339 in this molecule. Comparable cleavages were observed in bovine factor IX by bovine thrombin and occurred at Arg319-Ser320 and Arg339-Ser340. Essentially, a complete loss of factor IX procoagulant activity was associated with its cleavage by thrombin. Furthermore, thrombin-cleaved factor IX neither developed coagulant activity after treatment with factor XIa nor inhibited the coagulant activity of native factor IX. These data indicate that thrombin cleaves factor IX near its active site serine residue, rendering it incapable of activating factor X. Whether or not this reaction occurs in vivo is unknown.

Protein engineering of the propeptide of human factor IX

1991 ◽  
Vol 4 (3) ◽  
pp. 319-323 ◽  
Author(s):  
P.A. Handford ◽  
P.R. Winship ◽  
G.G. Brownlee
Keyword(s):  
Protein Engineering ◽  
Human Factor ◽  
Factor Ix ◽  
Human Factor Ix
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