Christmas Disease

Biggs, Rosemary; Douglas, A. S.; Macfarlane, Robert; Dacie, J. V.; Pitney, W. R.; Merskey,

doi:10.1136/bmj.2.4799.1378

Cited by 371 publications

(36 citation statements)

References 4 publications

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“…The disease affects approximately 1 in 30,000 males and is distributed equally among ethnic groups (1,2). The clinical presentation of the disease can be mild, moderate, or severe and is clinically indistinguishable from classic hemophilia A due to factor VIII deficiency (3,4). Hemophilia B results from the absence of normal factor IX, a plasma serine protease that converts factor X to its active form, thereby propagating the well-orchestrated coagulation cascade (5).…”

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confidence: 99%

A factor IX-deficient mouse model for hemophilia B gene therapy

Wang

Zoppé

Hackeng

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

161

125

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We have generated a mouse where the clotting factor IX (FIX) gene has been disrupted by homologous recombination. The FIX nullizygous (؊͞؊) mouse was devoid of factor IX antigen in plasma. Consistent with the bleeding disorder, the factor IX coagulant activities for wild-type (؉͞؉), heterozygous (؉͞؊), and homozygous (؊͞؊) mice were 92%, 53%, and <5%, respectively, in activated partial thromboplastin time assays. Plasma factor IX activity in the deficient mice (؊͞؊) was restored by introducing wild-type murine FIX gene via adenoviral vectors. Thus, these factor IX-deficient mice provide a useful animal model for gene therapy studies of hemophilia B.

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mentioning

confidence: 99%

A factor IX-deficient mouse model for hemophilia B gene therapy

Wang

Zoppé

Hackeng

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

161

125

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“…Like several other plasma proteinsi.e., prothrombin, Factor X, Factor VII, Protein C, and Protein S-Factor IX requires vitamin K for its biosynthesis (2)(3)(4). Individuals lacking Factor IX (Christmas disease or hemophilia B) show bleeding symptoms essentially identical to those of classic hemophilia or hemophilia A (Factor VIII deficiency) (5,6). The activity of Factor IX is also depressed in the plasma of patients treated with coumarin analogs, but in such cases the effect can be reversed by the administration of vitamin K (6).…”

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confidence: 99%

Comparison of amino acid sequence of bovine coagulation Factor IX (Christmas Factor) with that of other vitamin K-dependent plasma proteins.

Katayama¹,

Ericsson²,

Enfield³

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

140

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The amino acid sequence of bovine blood coagulation Factor IX (Christmas Factor) is presented and compared with the sequences of other vitamin K-dependent plasma proteins and pancreatic trypsinogen. The 416-residue sequence of Factor IX was determined largely by automated Edman degradation of two large segments, containing 181 and 235 residues, isolated after activating Factor IX with a protease from Russell's viper venom. Subfragments of the two segments were produced by enzymatic digestion and by chemical cleavage of methionyl, tryptophyl, and asparaginyl-glycyl bonds.Comparison of the amino acid sequences of Factor IX, Factor X, and Protein C demonstrates that they are homologous throughout. Their homology with prothrombin, however, is restricted to the amino-terminal region, which is rich in y-carboxyglutamic acid, and the carboxyl-terminal region, which represents the catalytic domain of these proteins and corresponds to that of pancreatic serine proteases. Factor IX (Christmas Factor) is the zymogen of a serine protease that participates in the middle phase of the intrinsic pathway of blood coagulation (1). Like several other plasma proteinsi.e., prothrombin, Factor X, Factor VII, Protein C, and Protein S-Factor IX requires vitamin K for its biosynthesis (2-4). Individuals lacking Factor IX (Christmas disease or hemophilia B) show bleeding symptoms essentially identical to those of classic hemophilia or hemophilia A (Factor VIII deficiency) (5, 6). The activity of Factor IX is also depressed in the plasma of patients treated with coumarin analogs, but in such cases the effect can be reversed by the administration of vitamin K (6).Bovine and human Factors IX have been purified and characterized (7)(8)(9)(10)(11)(12) Previous comparison of the partial sequence of bovine Factor IX with the sequences of bovine prothrombin and Factor X revealed homologous regions, indicating that these three proteins may have evolved from a common ancestral protein (16,17). Recently, the light and heavy chains of bovine Protein C, another vitamin K-dependent plasma protein, have been found to be homologous with Factor X (18,19). In the present communication, the complete sequence of Factor IX is presented.Comparison with the sequences of Factor X, Protein C, and prothrombin reveals areas of homology as well as regions lacking obvious similarity. The experimental details of the sequence determination will be published elsewhere. METHODS Factor IX, isolated from bovine plasma (7) and converted to Factor IXaa by a protease from Russell's viper venom (15), was obtained through the courtesy of K. Fujikawa. Factor IXaa was reduced with dithioerythritol and S-alkylated with 4-vinylpyridine. The two peptide chains (segment N and segment C) were separated on a column of SP-Sephadex C-25 by applying a linear gradient of sodium formate buffers in the presence of 7 M urea (20).Segment N (residues 1-181) was divided into two fragments (CB I and CB II), by cleavage with cyanogen bromide under conditions that avoid cleavage at y-carbo...

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“…This is particularly noticeable in suspected thromboplastin deficiencies, because of the lack of techniques which give quantitative results. Blood contains at least two plasma precursors of thromboplastin; anti-haemophilic globulin (Lewis et al, 1946;Brinkhous et al, 1951) and plasma thromboplastin component (PTC), also known as Christmas factor (Aggeler et al, 1952;Biggs et al, 1952). The two components have been called a-and ^-prothromboplastin respectively (Fantl and Sawers, 1954).…”

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confidence: 99%

Thrombin Formation and Yield in Shed Blood in Relation to Thromboplastins and Prothromboplastins

Fantl

1954

Aust J Exp Biol Med

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The experiments to be described were undertaken to provide an understanding of the defect in haemorrhagic tendencies connected with the thromboplastin complex. Tn severe haemorrhagic conditions, due to a deficiency of a clotting component, laboratory findings usually correlate well with elinical symptoms, but in a few cases it is difficult to decide whether the haemorrhages are due to a deficiency of a clotting component or to other causes. This is particularly noticeable in suspected thromboplastin deficiencies, because of the lack of techniques which give quantitative results. Blood contains at least two plasma precursors of thromboplastin; anti-haemophilic globulin (Lewis et al., 1946;Brinkhous et al., 1951) and plasma thromboplastin component (PTC), also known as Christmas factor (Aggeler et al., 1952;Biggs et al, 1952). The two components have been called a-and ^-prothromboplastin respectively (Fantl and Sawers, 1954). These are converted on certain surfaces to a-and ^-thromboplastin; the latter two, as well as adequate numbers of thromboeytes and calcium ions, form the blood thromboplastin complex. This reacts with the prothrombin system and thrombin is formed. In addition, blood contains factors which inactivate thrombin. The amount of thrombin which is present in clotting blood at a given moment depends therefore on the balance between formation and inactivation. Under these conditions it is obviously not possible to obtain quantitative results. Recently it was shown that phenols have the property of delaying the inactivation of thrombin by plasma (Fantl, 1954). In the presence of phenols it should be possible to assess quantitatively the ability of a system to form thrombin. With this deviee the relationship between thromboplastin activity and rate of formation and yield of thrombin was investigated. EXPERIMENTAL.Human venous blood was obtained by puncture of an arm vein. Arterial blood was aspirated from the femoral artery. In both cases the first few ml. were discarded. Nine I Part of the expenses of this investigation were defrayed by a grant from the National Health and Medical Reaearch Council, Australia.AustraL J. txp. BioL (1954), 32, pp. 853-866.

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Christmas Disease

Cited by 371 publications

References 4 publications

A factor IX-deficient mouse model for hemophilia B gene therapy

A factor IX-deficient mouse model for hemophilia B gene therapy

Comparison of amino acid sequence of bovine coagulation Factor IX (Christmas Factor) with that of other vitamin K-dependent plasma proteins.

Thrombin Formation and Yield in Shed Blood in Relation to Thromboplastins and Prothromboplastins

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