Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sera from 63 patients with haemophilia A, 21 with haemophilia B and 29 with von Willebrand's disease were screened for the presence of circulating immune complexes (CICs), serological markers of hepatitis A and B virus, autoantibodies and factor VIII or factor IX inhibitors. CICs were detected by the 125J Clq binding assay (ClqBA), the solid phase conglutinin assay (KgBSP) and the solid phase Clq assay (ClqSP). The incidence of CICs detected by the ClqBA and the ClqSP methods in haemophiliacs and in von Willebrand patients was higher than that observed in normal subjects, while the prevalence of CICs detected by the KgBSP method was not. The presence of CICs was not correlated with patient age, severity of disease, presence of hepatitis B virus serological markers, abnormal liver function tests or factor VIII inhibitors. A significant connection was demonstrated between CICs detected by the ClqBA method and replacement therapy when the dose administered over 1 year was over 20 000 U of factor VIII or IX concentrates. The high proportion of CICs in von Willebrand's disease, not connected with the replacement therapy or the presence of serological markers of hepatitis virus, is in agreement with the possibility that immune complexes may be related to the disease itself and independent, at least in part, of exogenous agents.
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PMID:Circulating immune complexes in haemophilia and von Willebrand's disease. 660 14

The efficacy of combined beta-propiolactone/ultraviolet irradiation (betaPL/UV) for inactivation of hepatitis B virus in labile blood derivatives has been reviewed. The initial evaluations of these procedures were hampered by inadequate process control that resulted in excessive protein denaturation; furthermore, adequate evaluation of process efficacy for virus inactivation was prevented by the absence of titered hepatitis virus stocks, the lack of an animal model, and the failure to carry out controlled trials. Finally, it was not appreciated that the power of these procedures lay especially in their use in combination. These deficits have now been remedied. To permit quantitation of process efficacy, a regression analysis of the relation between virus dose and incubation period in chimpanzees has been carried out. This has provided a means of estimating virus titer and determining the accuracy of such estimates. The most recent data suggest that betaPL/UV can reduce the titer of hepatitis B virus about 10 million fold (10(-7)). The process efficacy for betaPL/UV followed by the special adsorption procedures used in preparation of a stabilized human serum containing most human serum proteins except for factor VIII, the factor IX complex, fibrinogen, and the lipoproteins was estimated as a 10(8)-fold reduction in virus titer. This degree of virus inactivation should be more than sufficient to sterilize the amounts of hepatitis B virus that could be expected in pooled human plasma that has been screened for hepatitis B surface antigen. Preliminary data also suggest that the betaPL/UV procedure effectively inactivates non-A, non-B hepatitis virus(es).
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PMID:beta-propiolactone/ultraviolet irradiation: a review of its effectiveness for inactivation of viruses in blood derivatives. 682 13

Recent experiments have shown that a preparation of PPSB (factor IX concentrate) derived form beta PL/UV treated plasma was not infectious in chimpanzees with respect to hepatitis B and non-A, non-B. To answer the question whether the beta PL/UV treatment influences the tolerance and efficacy of the PPSB-concentrate, long-term application of PPSB-Biotest was carried out in chimpanzees. After 10 applications of 25 U factor IX/kg at weekly intervals, no signs of intolerance were observed by measurement of blood pressure during i.v. application and by means of skin-testing. Determination of coagulation factor activity during the application period revealed the same factor IX recovery at the beginning and at the end of the study.
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PMID:Long-term tolerance and recovery of beta-propiolactone/ultraviolet (beta PL/UV) treated PPSB in chimpanzees. 730 90

Selection of an optimal promoter is necessary for efficient expression of foreign genes with vaccinia virus. Since a variety of powerful (homologous) vaccinia virus promoters and foreign (heterologous) promoter systems have been described for use in vaccinia, we have addressed the question of whether a general rule exists that allows the prediction of the optimal promoter/gene combination. We have compared the expression properties of four secreted proteins, the human blood clotting factor IX (FIX), the human blood glycoprotein Protein S (ProtS), the human von Willebrand factor (vWF), and the Hepatitis B virus (HBV) middle surface glycoprotein preS2, with proteins that were reported not to be secreted, the HBV large surface glycoprotein preS1 and the murine leukemia virus (MuLV) BM-5 Eco gag protein. In addition, we have included in our study an internal control protein, the vaccinia virus p11 protein, to monitor possible side effects of the promoter system used. Genes encoding the foreign proteins were placed either under control of a synthetic vaccinia virus early/late promoter (selP) or under control of the bacteriophage T7 promoter (T7/emc system). The secreted proteins were more efficiently expressed when fused to the homologous promoter. Direct comparison of the two promoters indicated that the expression level ranged between 1.4 (ProtS) and 3.9 (FIX)-fold higher with the selP than with the T7 promoter. In contrast, the cell-associated HBV preS1 was more efficiently expressed under the T7 promoter and the MuLV BM-5 Eco gag polypeptide was expressed equally well from both promoters. These data indicate that a careful prediction of optimal promoter/foreign gene combinations for the vaccinia virus expression system is possible. The choice of the optimal promoter/expression system is based on a simple classification scheme, discriminating secreted and nonsecreted proteins.
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PMID:Requirements for optimal expression of secreted and nonsecreted recombinant proteins in vaccinia virus systems. 853 47

Liver transplantation is a treatment modality that is being used with increasing frequency in cases of liver-based metabolic defects. This is a case report of a patient with hemophilia B who was treated since childhood with factor IX replacement for recurrent hemarthroses. Subsequent hepatitis B (HBV) and C (HCV) infection had resulted in the development of chronic active hepatitis, ultimately leading to cirrhosis. Orthotopic liver transplantation performed for endstage liver disease resulted in a rise in factor IX levels from 2% to 83% of normal values within 24 h postoperatively, and levels remained above 90% of normal values after postoperative day 3 without factor IX replacement. To our knowledge, only two cases of hemophilia B treated by orthotopic liver transplantation have been reported. This procedure has, however, only been implemented in cases of terminal liver insufficiency in hemophiliacs.
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PMID:Orthotopic liver transplantation in hemophilia B: a case report. 857 41

The safety and efficacy of a monoclonal antibody purified factor IX concentrate were evaluated in two continuing trials of 32 previously untreated patients with mild, moderate, or severe hemophilia B. Patients were evaluated every 2 weeks for 24 weeks and every 3 months thereafter for at least 1 year. No patients became positive for human immunodeficiency virus antibody or hepatitis C virus antibody during the trial. Two patients developed a false-positive hepatitis B core antibody, one transiently, but neither had elevated levels of alanine aminotransferase (ALT). None of the 25 patients evaluable for non-A, non-B, non-C hepatitis by strict International Society of Thrombosis and Hemostasis criteria developed elevated levels of ALT indicative of posttransfusion infection. Anaphylaxis occurred in one subject who also developed an inhibitor to factor IX (19.3 Bethesda units). Five of the eight adverse events reported (63%) were mild in severity, and the relationship of three of these to therapy was considered remote. Hemostasis with monoclonal antibody purified factor IX concentrate was excellent in all patients.
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PMID:Safety and efficacy of monoclonal antibody purified factor IX concentrate in previously untreated patients with hemophilia B. 871 76

Several different designs for retroviral and adeno-associated virus (AAV) vectors were developed to express human clotting factor IX. Seven separate retroviral vectors were constructed, including chimeric long terminal repeat (LTR)-based designs, vectors containing splice donor/acceptor sites with internal ribosome entry sites (IRES), and vectors with an internal cytomegalovirus (CMV)- or hepatitis B virus (HBV)-derived promoter. Five AAV vectors were produced using the same cassette design where a viral promoter was used to transcribe a bicistronic mRNA containing factor IX and an IRES/neo gene. In the human hepatocyte cell line HepG2, the constructs were tested for factor IX production by ELISA, Northern blot, and Western blot, and for biological activity by normalization of the prolonged activated partial thromboplastin time (APTT) of factor IX-deficient plasma. All of the constructs produced biologically active factor IX in the range of 0.23-152 ng/24 hr per 10(6) cells (the HBV-promoted factor IX AAV vector was the least effective, and the CMV-promoted retroviral vector was the most active). Primary fibroblasts of both human and rabbit origin were also evaluated for factor IX production following transduction with viral vectors. Fibroblasts produced substantially more factor IX than the HepG2 cell line, with the best AAV vector synthesizing > 250 ng/24 hr per 10(6) cells and the best retroviral vector making > 900 ng/24 hr per 10(6) cells. Generally, we observed lower transduction efficiency and poorer expression with the AAV vectors versus retroviral vectors in these cell types.
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PMID:Comparison of retroviral and adeno-associated viral vectors designed to express human clotting factor IX. 901 17

The present study summarizes the results of 12 cardiac surgical procedures performed in a carrier of Haemophilia B and in six patients with Haemophilia A at a single centre from 1979 to 1998. The median age of the patients at the time of intervention was 56 years ranging from 18 years to 73 years. The six patients with Haemophilia A ranged in severity from moderately to mildly affected. Three patients were hepatitis C antibody positive. No patients were HIV antibody or hepatitis B surface antigen positive. The cardiac procedures included cardiac catheterization (n=4), coronary artery bypass surgery (n=2), percutaneous transluminal coronary angioplasty (n=1), cardiac valve replacement (AVR n=1 and AVR/MVR n=2), and closure of an atrial septal defect and subsequent drainage of a pericardial effusion (n=1). No patients had demonstrable inhibitors at the time of surgery. Haemostasis was achieved with AHF in 10/11 procedures and high purity factor IX (Immunine) in one procedure. The initial procedures involved intermittent bolus factor therapy while more recently, AHF was administered by continuous intravenous infusion. All patients demonstrated excellent intra- and post-operative haemostasis. These results, although from a small and varied group of patients, demonstrate that cardiac surgical procedures can be performed safely in patients with Haemophilia.
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PMID:Cardiac surgery and catheterization in patients with haemophilia. 1078 Nov 93

The epidemics of HIV and hepatitis C in treated haemophiliacs spurred rapid technological advances in the viral safety of clotting factor concentrates produced from large donor pools. Sequential steps are now employed to minimize infectious risks. The initial viral burden is reduced by screening donors and by testing individual donations and plasma pools for antivirus antibodies, viral antigens, and nucleic acid. These techniques are supplemented by nonspecific viral reduction steps based on physical partitioning and inactivation of pathogens by physical (eg, heat) or chemical (eg, solvent-detergent) means. Although these processes have virtually eliminated the transmission of HIV and hepatitis B and C, there is still evidence that concentrates can transmit small nonenveloped viruses, such as parvovirus B19 and hepatitis A virus. Furthermore, new agents which may not be susceptible to current viral inactivation procedures continue to be identified. Concerns such as these have also given impetus to the development of recombinant clotting factor proteins. Recombinant factor IX concentrate is now produced without the use of human plasma proteins at any step in the manufacturing or formulation process. In practice, the risk of viral transmission by clotting factor concentrates is now so remote that any manipulations to further reduce this risk may be counter-productive, by enhancing cost (hence compromising availability) and potentially promoting other adverse effects such as immunogenicity.
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PMID:Viral safety of haemophilia treatment products. 1108 69

Using the polymerase chain reaction (PCR), we designed a study concept to evaluate the safety of plasma derivatives in previously treated patients who are non-infected by the specific viruses studied. Several product lots can be studied in a single patient, with a study period for each lot of 3 months. In the present study 19 patients were included for treatment with Baxter Hyland Immuno's PCR-screened factor VIII concentrate Immunate (n=7), factor IX concentrate Immunine (n=10), the by-passing agent FEIBA plus Immunine (n=1), and the protein C concentrate Ceprotin (n=1). PCR testing for hepatitis B, C or HIV genomic material in patient samples was done as well as serological testing. All patients remained negative for the tested markers. All seven Immunate patients completed three treatment periods with three different lots of the study drug. The median study period was 282 days and the median dose 115 000 units, with a median of 115 exposure days. Five of the 10 Immunine patients completed three treatment periods and four patients, two treatment periods. One Immunine patient was discontinued from the study for reasons unrelated to the study drug administration. The median study period was 305 days and the median total dose 82 200 units, with a median of 88 exposure days. Our study presents a new design to approach the evaluation of viral safety of new plasma derivatives in previously treated, non-infected patients (NIPs) and offers several advantages over the currently recommended studies using testing for serological markers of infection in previously untreated patients (PUPs).
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PMID:An approach to study the viral safety of plasma-derived products in previously treated, non-infected patients. 1144 39


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