Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “FACTOR IX”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 919 records · Page 51Linked to original sources
PubMed1998

Viral safety of recombinant factor IX.

The viral safety of Chinese hamster ovary (CHO)-cell-based pharmaceuticals is well established. There have been more than 100 million infusions of CHO-derived pharmaceuticals without a single documented case of viral transmission. The recombinant factor IX (rFIX) process builds on this safety record by using a state-of-the-art multitiered approach to viral safety. This includes extensive testing of the CHO cells used to produce rFIX, routine viral monitoring of the cell culture production process, a manufacturing process and formulation that do not use blood or plasma products, and validation of the viral removal capacity of the purification process. The multifaceted viral safety program for rFIX has sufficient redundancy between approaches to compensate for potential limitations of any single safety measure. Together, the elements of the rFIX multitiered viral safety program offer patients and physicians a product that is inherently free of human blood-borne pathogens, including any risk of human immunodeficiency virus (HIV) hepatitis, parvovirus, and Creutzfeldt-Jakob disease (CJD).

Animals↗
PubMed1993

[A PCR-system of analyzing polymorphic markers in gamma-A and gamma-G globin genes and gene for human blood coagulation factor IX with an internal control of the completeness of restriction hydrolysis].

New systems are proposed for the PCR analysis of HindIII polymorphic sites in the gamma A and gamma G globin genes and of TaqI polymorphic site in the human factor IX gene of blood population. DNA fragments amplified according to the systems described contain constant restriction site of the appropriate endonuclease, in addition to the polymorphic one, which significantly improves the reliability of the RELP analysis. The systems proposed are highly specific and may be used for DNA diagnosis of beta-thalassemia and haemophilia B.

Base Sequence↗
PubMed1994

The rates of G:C-->T:A and G:C-->C:G transversions at CpG dinucleotides in the human factor IX gene.

We have identified eight independent transversions at CpG in 290 consecutive families with hemophilia B. These eight transversions account for 16.3% of all independent transversions in our sample, yet the expected frequency of CpG transversions at random in the factor IX gene is only 2.6% (P < .01). The aggregate data suggest that the two types of CpG transversions (G:C-->T:A and G:C-->C:G) possess similar mutation rates (24.8 x 10(-10) and 20.6 x 10(-10), respectively), which are about fivefold greater than the comparable rates for transversions at non-CpG dinucleotides. The enhancement of transversions at CpG suggests that the model by which mutations occur at CpG may need to be reevaluated. The relationship, if any, between deamination of 5-methyl cytosine and enhancement of transversions at CpG remains to be defined.

Amino Acid Sequence↗
PubMed2000

Factor IX gene sequencing by a simple and sensitive 15-hour procedure for haemophilia B diagnosis: identification of two novel mutations.

We have developed a simple, sensitive and cost-effective direct DNA sequencing procedure for the molecular diagnosis of haemophilia B. All factor IX gene essential regions were amplified under identical thermocycling parameters allowing mutation identification in less than 15 h from blood sample collection. Identical results in terms of accuracy and speed were obtained when using a single hair as the source of DNA. Using this approach, we have found mutations in 10 out of 10 haemophilia B patients, two of which are novel (P287T and S123C). Very suitable for individual studies, this procedure can be easily scaled up for higher throughput.

Electronic Data Processing↗
PubMed1975

A five year experience of the use of factor IX type DE(I) concentrate for the treatment of Christmas disease of Oxford.

A survey is presented of the use of the Oxford type DE(I) II-IX-X concentrate in the treatment of Christmas disease in Oxford from January 1970 to September 1974. 72 different patients were treated with a total of 2436 bottles of this concentrate from 143 different batches (each bottle containing 800-1000 units of factor IX). Although most doses were given for the treatment of minor haemorrhages into joints and muscles, 717 bottles of concentrate were used to treat 11 patients who underwent 14 major surgical operations. No episode of intravascular clotting or pulmonary embolism was seen in any patient receiving the concentrate. A detailed study of the plasma levels of factor V, VIII, total progressive antithrombin, platelets and fibrinogen degradation products was carried out before and after transfusion of type DE(I) concentrate in 14 patients. No significant alteration in those factors was found after the transfusion.

Antithrombins↗
PubMed1989

The factor IX BamHI polymorphism: T-to-G transversion at the nucleotide sequence -561. The BamHI/MSPI haplotypes in blacks and Caucasians.

The polymerase chain reaction (PCR) method was used to amplify a 356-bp DNA segment containing the suspected BamHI polymorphic site of the factor IX gene. Following the enzyme digestions and gel electrophoresis, polymorphic genotypes (-,+ and +/- types) were observed. The gene frequencies for the rare (+) allele are about 36% in blacks and 2% in Caucasians. The 356-bp DNA was further purified and sequenced. The sequencing gels revealed a single nucleotide substitution (T to G) at position -561 of the gene in blacks and Caucasians. The T-to-G transversion generated a new BamHI site (GGATCC,+type) from a nonenzymatic site, (TGATCC,-type).

Base Sequence↗
PubMed1997

Missense mutations at ALA-10 in the factor IX propeptide: an insignificant variant in normal life but a decisive cause of bleeding during oral anticoagulant therapy.

Bleeding complications are the most common and unwanted side-effect of oral anticoagulant therapy. We report three patients in whom mutations in the factor IX (FIX) propeptide were found to cause severe bleeding during coumarin therapy. Strikingly, the bleeding occurred within the therapeutic ranges of the prothrombin time (PT) and international normalized ratio (INR). In all three patients coumarin therapy caused an unusually selective decrease of FIX activity (FIX:C) to levels below 1-3%. Upon withdrawal of coumarin, FIX:C increased to subnormal or normal values of 55%, 85% and 125%, respectively. Analysis of the FIX gene revealed two different missense mutations affecting the Ala-10 residue in the propeptide coding region: Ala[GCC] to Val[GTC] in two patients and Ala[GCC] to Thr[ACC] in one patient. No further mutation was detected by screening 195 random blood donors for mutations at Ala-10, thus excluding a frequent polymorphism at this position. The mutation in the FIX propeptide at a position which is essential for the carboxylase recognition site causes a reduced affinity of the carboxylase enzyme to the propeptide. This effect leads to an impaired carboxylase epoxidase reaction which is decisively triggered by the vitamin K concentration. Determination of FIX and APTT in addition to PT and INR is therefore recommended in coumarin-treated patients with an uncommon bleeding pattern.

Administration, Oral↗
PubMed1983

Laboratory evaluation of factor VIII and factor IX.

It appears the state of the art of evaluating factors VIII and IX is in its infancy. With the exception of the screening tests, the more specific methodologies are expensive, time-consuming, and require a certain amount of technical proficiency for proper performance. However, our ability to evaluate these molecules has advanced greatly since the early 1970s. Most probably the methods described in this paper will be available in the near future to all laboratories wishing to perform them, either in kit form or in a more simplified version. Meanwhile, the APTT, mixing tests, qualitative factor assays, and bleeding times may be performed by nearly any laboratory. The performance of these tests will help identify those patients who may have potentially life-threatening postoperative bleeding episodes or who are having a bleeding episode that requires diagnosis for effective treatment. It is therefore important that these tests be incorporated into our routine coagulation protocols.

Antigens↗
PubMed1988

Identification of a CpG mutation in the coagulation factor-IX gene by analysis of amplified DNA sequences.

In a family with no previous bleeding history, the sister of a single, severely affected haemophilia B patient requested carrier detection and prenatal diagnosis. In Southern blots, using Taq I digested DNA and a factor-IX cDNA probe, a normal invariant band at 1.6 kb was missing in the haemophiliac suggesting the loss of the Taq I site at the 5' end of exon h. A 162 bp sequence which includes the suspected mutant region was amplified by the polymerase chain reaction in each DNA. Two oligonucleotide probes were synthesized and differed by only one base pair which substituted a T for C in the normal Taq I recognition sequence. The amplified DNA was dot-blotted and hybridized with the labelled probes. The altered sequence hybridized to DNA from the affected individual, his sister and her fetus and not to DNA from the normals. The mutation, involving the haemophiliac, his mother, his sister and her fetus, transforms a CGA codon that encodes for arginine in the catalytic domain of the protein into a UGA stop codon.

Adult↗
PubMed1987

A DNA marker closely linked to the factor IX (haemophilia B) gene.

We have isolated a DNA segment, pX58dIIIc, from an X-chromosome library which identifies an SstI restriction fragment length polymorphism (RFLP) at locus DXS99. Linkage analysis in six informative families has shown that the DXS99 locus lies close to the factor IX gene (F9). No recombination was detected between these loci in 39 informative meioses (Z = 9.79, theta = 0.0). Therefore, DXS99 will be useful as a DNA marker for the assessment of carrier status in families with haemophilia B where intragenic markers are not informative. Heterozygosity at DXS99 is approximately 50% and, in conjunction with the RFLPs at F9, 90% of females at risk for being haemophilia B carriers should be diagnosed.

Factor IX↗
PubMed1995

Detection of ten new mutations by screening the gene encoding factor IX of Danish hemophilia B patients.

Hemophilia B is caused by a wide range of mutations. In order to characterize the mutations among patients in Denmark, we have systematically screened the entire coding region, the promoter region and exon flanking sequences of the gene encoding factor IX using single strand conformation and heteroduplex analyses. Patients from 32 different families were examined, and point mutations (23 different) were found in all of them. Ten of the mutations have not been reported by others; they include a splice site mutation, a single base pair deletion, and missense mutations. Notably, the study contains a female patient and a previously described Leyden mutation. In ten families with sporadic cases of hemophilia B, all 10 mothers were found to be carriers. The origin of two of these mutations was established.

Base Sequence↗
PubMed1980

Anti-factor IX circulating anticoagulant and immune thrombocytopenia in a case of Takayasu's arteritis.

A 38-year-old male with proven Takayasu's arteritis presented, in a routine investigation, with thrombocytopenia, prolonged whole blood clotting time and activated partial thromboplastin time. Further studies demonstrated low levels of factor IX caused by a circulating anticoagulant. Immunological studies revealed an IgG (with kappa chains predominance) nature of this. Corticoid therapy decreased but did not suppress the anticoagulant activity. Since similar coagulation abnormalities have been described in collagen diseases, this observation is in support of this etiology to be considered in Takayasu's arteritis.

Adult↗
PubMed1983

Further evaluation of a heparin neutralizer and its effect on factor IX in normal and coumadin-plasma.

Heparsorb, a commercial anion exchange resin capable of removing large amounts of heparin from heparinized plasma, has recently been introduced into the clinical diagnostic laboratory as a useful reagent for the evaluation of blood coagulation in heparinized blood and the evaluation of an unexpected prolongation of global coagulation tests. In this paper data are presented which indicate that Heparsorb has little or no effect on the activities of blood coagulation factors in heparinized plasma, except for a modest (22%) reduction in factor IX-activity. Maximal loss of factor IX-activity was observed after incubation of plasma with Heparsorb for 15 min at room temperature. Prolonged storage of plasma before or after incubation with Heparsorb and changes in plasma pH had no appreciable effect on the extent of factor IX-activity loss. Evidence is presented to substantiate earlier findings that factor IX-activity is not removed by Heparsorb from plasma of patients on coumadin therapy, and to indicate that this lack of effect of Heparsorb on factor IX-activity in coumadin plasma is due to reduced affinity of hypocarboxy-IX for the heparin neutralizing resin.

Blood Coagulation Tests↗
PubMed1998

Stability of nonaqueous suspension formulations of plasma derived factor IX and recombinant human alpha interferon at elevated temperatures.

PURPOSE: To identify a suitable nonaqueous, parenterally acceptable suspending vehicle whereby a therapeutic protein is delivered as a stable flowable powder, making it amenable to delivery from sustained delivery systems maintained at body temperature. METHODS: Formulations of plasma derived Factor IX (pdFIX) and recombinant human alpha interferon (rhalpha-IFN) were formulated as dry powders, suspended in various vehicles (perfluorodecalin, perfluorotributylamine, methoxyflurane, polyethylene glycol 400, soybean oil, tetradecane or octanol) and stored at 37 degrees C. Stability was assessed by size exclusion chromatography, reverse phase chromatography, ion exchange chromatography, and bioassay, and was compared to the stability of dry powder formulations stored at 37 degrees C and -80 degrees C. RESULTS: PdFIX was stable when stored at 37 degrees C as a dry powder, or when the dry powder was suspended in the pharmaceutically acceptable vehicles perfluorodecalin or perfluorotributylamine. Suspensions of the powder in other pharmaceutically/parenterally acceptable vehicles such as soybean oil or PEG 400 resulted in aggregation and loss of bioactivity. A dry powder formulation of rhalpha-IFN suspended in perfluorodecalin was also stable at 37 degrees C. CONCLUSIONS: This study shows the potential utility of perfluorinated hydrocarbons as nonaqueous suspending vehicles for long term in-vivo delivery of therapeutic proteins.

Antineoplastic Agents↗
PubMed2002

Production of human clotting Factor IX without toxicity in mice after vascular delivery of a lentiviral vector.

Replication-deficient lentiviral vectors (LV) have been shown to enable the stable genetic modification of multiple cell types in vivo. We demonstrate here that vascular and hepatic delivery of a third-generation HIV-derived lentiviral vector encoding human Factor IX (LV-hFIX) produced potentially therapeutic serum levels of hFIX protein with no vector-mediated local or systemic toxicity of adult mice. Portal vein administration produced the highest serum levels of hFIX and demonstrated proportionally higher levels of gene transfer to the liver with up to 4% of hepatocytes expressing hFIX. Vascular delivery of a lentiviral vector encoding GFP resulted in genetic modification of up to 12% of liver cells. Cell proliferation was not required for hepatocyte transduction with either vector. Serum hFIX levels reached 4% of normal levels following vascular LV-mediated hFIX gene transfer and remained stable for months following vector administration.

Animals↗