Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The treatment of plasma with organic solvent/detergent mixtures at the time of plasma collection or pooling could reduce the exposure of technical staff to infectious viruses and enhance the viral safety of the final product. Treatment of plasma for 4 hours with 2-percent tri(n-butyl)phosphate (TNBP) at 37 degrees C, with 1-percent TNBP and 1-percent polyoxyethylensorbitan monooleate (Tween 80) at 30 degrees C, or with 1-percent TNBP and 1-percent polyoxyethylene ethers, (Triton X-45) at 30 degrees C resulted in the rapid and complete inactivation of greater than or equal to 10(4) tissue culture-infectious doses (TCID50) of vesicular stomatitis and Sindbis viruses, which are used as surrogates. Treatment of plasma with TNBP and TNBP and Tween-80 was shown to inactivate greater than or equal to 10(4) TCID50 of human immunodeficiency virus. TNBP treatment of plasma contaminated with 10(6) chimpanzee-infectious doses (CID50) of hepatitis B virus and 10(5) CID50 of non-A,non-B hepatitis virus prevented the transmission of hepatitis to chimpanzees. Immediately after treatment of plasma with 2-percent TNBP, the recovery of factors VIII, IX, and V and antithrombin III was 80, 90, 40, and 100 percent, respectively. Recovery of all factors was greater than or equal to 90 percent after treatment with TNBP and detergent mixtures. Treated plasma was fractionated by standard techniques into antihemophilic factor and prothrombin complex concentrates, immune globulin, and albumin. Prior treatment with TNBP or TNBP and detergent did not affect the separations of desired proteins. Therefore, it appears possible to inactivate viruses in plasma before the execution of standard fractionation procedures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The use of tri(n-butyl)phosphate detergent mixtures to inactivate hepatitis viruses and human immunodeficiency virus in plasma and plasma's subsequent fractionation. 175 94

In the last decade it appeared more than once that blood donations were contaminated by hitherto unknown viruses. Due to this fact, further steps have to be included into the manufacturing procedure of even up to now safe products from human plasma to eliminate potential new risks. A procedure is described which enables the pasteurization of antithrombin III analogous to albumin without major changes in the properties of the molecule. Thus the new product Kybernin HS/P was obtained. The efficacy of the pasteurization step was tested using relevant human pathogenic viruses. The following titers of important viruses could be totally inactivated within the pasteurization time (h) given in brackets HIV: (human immunodeficiency virus) greater than or equal to 10(6.7) (1), CMV (cytomegaly virus) greater than or equal to 10(4.5) (1), HSV (Herpes simplex virus) greater than or equal to 10(6.8) (4), Polio (poliomyelitis virus) greater than or equal to 10(6.9) (4).
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PMID:[Properties and virus safety of a pasteurized antithrombin III concentrate]. 282 38

Virus sterilization of blood plasma derivatives by addition of several naturally occurring fatty acids was evaluated using vesicular stomatitis virus and Sindbis virus as markers for lipid-enveloped virus inactivation and human immunodeficiency virus (HIV). Inactivation of greater than or equal to 10(4) tissue culture infectious doses (TCID50) of marker viruses added to antihemophilic factor (AHF) concentrates, with 60-100% retention of AHF activity, was achieved with oleic, 11-eicosenoic, linoleic, linolenic, palmitoleic and arachidonic acids. Elaidic, gamma-linolenic, palmitic, and arachidic acids and another fat-soluble compound previously reported to inactivate virus, butylated hydroxytoluene, were less effective. A long chain mono- but not a di- or triglyceride also displayed virucidal properties. Evaluation of the inactivation of HIV added to an immune globulin solution on exposure to 0.033% sodium oleate for 20 min indicated inactivation of greater than or equal to 10(3.4) TCID50. The degree of virus inactivation depended on the sample composition. A favorable balance was achieved between degree of virus inactivation and retention of protein function for AHF concentrate, prothrombin complex concentrate, antithrombin III concentrate, and immune globulin solution on incubation with 0.033% (w/v) sodium oleate at 24 degrees C for 4-6 h. Virus inactivation in whole plasma and plasma cryoprecipitate was not complete despite use of higher concentrations of sodium oleate and/or incubation at 37 degrees C. Reduced virus kill in these less purified derivatives probably is a consequence of their endogenous lipid and/or albumin.
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PMID:Inactivation of lipid-enveloped viruses in labile blood derivatives by unsaturated fatty acids. 283 69

Human immunodeficiency virus (HIV), isolated from cultures of infected peripheral blood lymphocytes, was added to solutions of highly purified antithrombin III (AT-III), which was stabilized with 1 M citrate and 17 percent sucrose. The efficiency of heat inactivation of HIV in AT-III at 60 degrees C was compared with that of HIV in culture medium and followed for periods from 0 to at least 10 hours. The virus added, titer 10(5) by ID50, was inactivated as rapidly (less than 30 minutes) and efficiently (completely) in the stabilized AT-III as in the culture medium. Virus was determined both by direct measurement of the HIV-related reverse transcriptase activity and by quantitation of virus infectivity by ID50 assay.
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PMID:Heat inactivation of human immunodeficiency virus in solutions of antithrombin III. 291 25

We have isolated overlapping phage genomic clones covering an area of 26 kilobases that encodes the human alpha 2-plasmin inhibitor. The alpha 2-plasmin inhibitor gene contains 10 exons and 9 introns distributed over approximately 16 kilobases of DNA. To our knowledge, the number of introns is the highest yet reported for a member of the serine protease inhibitor (serpin) superfamily. All introns are located in the 5'-half of the corresponding mRNA. The 5'-untranslated region and the leader sequence are interrupted by 3 introns totaling approximately equal to 6 kilobases. A "TATA box" sequence is located 17 nucleotides upstream from the proposed transcription initiation site. Multiple "GC box" sequences, G + C-rich sequences, and "CCAAT box"-like sequence, the hepatitis B virus enhancer element-like sequence and the human immunodeficiency virus enhancer-like sequence appear in the 5'-flanking region. The NH2-terminal region, which implements factor XIII-catalyzed cross-linking of alpha 2-plasmin inhibitor to fibrin, is encoded by the 4th exon. The reactive site and plasminogen-binding site, both located in the COOH-terminal region, are encoded by the 10th exon. When similar amino acids of alpha 2-plasmin inhibitor and other members of the serpin gene superfamily are aligned, the position of the 7th intron of the alpha 2-plasmin inhibitor gene aligns precisely with that of the second intron of the genes for rat angiotensinogen and human alpha 1-antitrypsin genes and is misaligned by only one nucleotide with that of the third intron of antithrombin III, suggesting that the alpha 2-plasmin inhibitor gene originates from the common ancestor of these serine protease inhibitors.
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PMID:Organization of the human alpha 2-plasmin inhibitor gene. 316 40

Blood derived products carry the risk of virus transmission, especially for the hepatitis B virus (HBV), non-A/non-B virus(es) (NANBV) and human immunodeficiency virus (HIV). The precautionary measures for guaranteeing the virus safety of the pasteurized antithrombin III concentrate Kybernin HS/P are described and the efficacy of these measures is demonstrated by in vitro studies and by chimpanzee trials. The inactivation rate is greater than or equal to 10(6.7) for HIV, greater than or equal to 10(6.7) for HBV, and greater than or equal to 10(5.3) for NANBV (Hutchinson Pool). Clinically, virus safety was demonstrated by long-term drug surveillance as well as by both a retrospective and prospective clinical trial. The 13 participants of the prospective study were checked clinically and biochemically according to the standards of the International Committee of Thrombosis and Hemostasis (ICTH). Within an observation period of 12 months, no seroconversion has been detected for HIV or HBV. Neither have any increases in the transaminases occurred which would indicate NANB hepatitis.
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PMID:Virus safety of a pasteurized antithrombin III concentrate. Preclinical and clinical data. 367 69

Human plasma-derived protein concentrates intended for clinical use must be treated for viral inactivation to ensure patient safety. This study explored the use of liquid iodine for inactivation of several lipid- and nonlipid-enveloped viruses in an antithrombin III (AT-III) concentrate. Iodine at levels of 0.01% to 0.02% caused between 43% and 94% loss of AT-III activity, as well as degradation of AT-III as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis. However, addition of up to 0.1% human albumin protected the AT-III against both inactivation and fragmentation. At albumin levels sufficient to retain greater than 75% of AT-III activity, greater than 6 logs of sindbis, encephalomyocarditis, and vesicular stomatitis viruses, greater than 4 logs of pseudorabies, and greater than 3 logs of human immunodeficiency virus were inactivated. Except with sindbis virus, this represented complete inactivation of all the viruses spiked into the AT-III concentrate.
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PMID:Iodine-mediated inactivation of lipid- and nonlipid-enveloped viruses in human antithrombin III concentrate. 760 9

It has previously been shown that the hepatitis B virus (HBV) X gene product, HBx, transactivates homologous and heterologous transcriptional regulatory sequences of viruses, including the human immunodeficiency virus type 1 (HIV1) long terminal repeat (LTR), and various cellular genes in vitro. To evaluate the transactivating function of HBx in vivo, we generated transgenic mice carrying the X open reading frame under the control of the human antithrombin III (ATIII) gene regulatory sequences. These mice express the 16 Kd HBx protein in the liver, as demonstrated by immunoprecipitation studies. Crossbreeding of HBx mice with transgenics carrying either the chloramphenicol acetyl transferase (CAT) bacterial or the lacZ reporter gene driven by the HIV1-LTR allowed us to demonstrate, for the first time, the in vivo transactivating function of HBx protein.
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PMID:The hepatitis B virus X gene product transactivates the HIV-LTR in vivo. 826 Aug 78

Measurements of the antithrombin III (AT III) activity in feline plasma with a thrombin dependent chromogenic substrate assay using an automatic analyzer showed a high within run precision. The coefficient of variance was 1.82% (normal AT III activity) or 3.19% (decreased AT III activity), respectively. In comparison with the feline pool plasma the AT III activity in canine plasma was similar (93.7%) and in human reference plasma was lower (71.7%). Respecting healthy cats aged more than three months no distinct influence could be demonstrated on the AT III activity neither of age nor of gender (p = 0.2180). Based on the 2.5%- and 97.5%- quantile the reference range was 83.5-122.5% respecting the total number of healthy cats (n = 138) or 82.6-121.5% concerning the 116 European Shorthair cats. AT III activity of cats infected with feline immunodeficiency virus (n = 37) or teline leukemia virus (n = 20) as well as of cats suffering from different solitary tumors (n = 8) was not distinctly different from the control group (p > 0.05). On the contrary, a significant decrease of AT III activity was found in traumatized cats (n = 20; median = 80.8%, p < 0.0001) as well as in animals with chronic renal failure (n = 20; median = 91.7%, p = 0.0228) which can be mainly attributed to a consumption reaction or excessive renal loss, respectively.
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PMID:[Antithrombin III activity in health cats and its changes in selected disease]. 945 44

CD8(+) T-cells secrete soluble factor(s) capable of inhibiting both R5- and X4-tropic strains of human immunodeficiency virus type 1 (HIV-1). CCR5 chemokine ligands, released from activated CD8(+) T-cells, contribute to the antiviral activity of these cells. These CC-chemokines, however, do not account for all CD8(+) T-cell antiviral factor(s) (CAF) released from these cells, particularly because the elusive CAF can inhibit the replication of X4 HIV-1 strains that use CXCR4 and not CCR5 as a coreceptor. Here we demonstrate that activated CD8(+) T-cells of HIV-1-seropositive individuals modify serum bovine antithrombin III into an HIV-1 inhibitory factor capable of suppressing the replication of X4 HIV-1. These data indicate that antithrombin III may play a role in the progression of HIV-1 disease.
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PMID:Purification of a modified form of bovine antithrombin III as an HIV-1 CD8+ T-cell antiviral factor. 1219 9


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