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)

Fresh frozen plasma (FFP) is prepared in blood banks world-wide as a by-product of red blood cell concentrate preparation. Appropriate clinical use is for coagulation factor disorders where appropriate concentrates are unavailable and when multiple coagulation factor deficits occur such as in surgery. Viral safety depends on donor selection and screening; thus, there continues to be a small but defined risk of viral transmission comparable with that exhibited by whole blood. We have prepared a virus sterilized FFP (S/D-FFP) by treatment of FFP with 1% tri(n-butyl)phosphate (TNBP) and 1% Triton X-100 at 30 degrees C for 4 hours. Added reagents are removed by extraction with soybean oil and chromatography on insolubilized C18 resin. Treatment results in the rapid and complete inactivation of greater than or equal to 10(7.5) infectious doses (ID50) of vesicular stomatitis virus (VSV) and greater than or equal to 10(6.9) ID50 of sindbis virus (used as marker viruses), greater than or equal to 10(6.2) ID50 of human immunodeficiency virus (HIV), greater than or equal to 10(6) chimp infectious doses (CID50) of hepatitis B virus (HBV), and greater than or equal to 10(5) CID50 of hepatitis C virus (HCV). Immunization of rabbits with S/D-FFP and subsequent adsorption of elicited antibodies with untreated FFP confirmed the absence of neoimmungen formation. Coagulation factor content was comparable with that found in FFP. Based on these laboratory and animal studies, together with the extensive history of the successful use of S/D-treated coagulation factor concentrates, we conclude that replacement of FFP with S/D-FFP, prepared in a manufacturing facility, will result in improved virus safety and product uniformity with no loss of efficacy.
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PMID:Solvent/detergent-treated plasma: a virus-inactivated substitute for fresh frozen plasma. 131 64

Exemplified on fifty peptides derived from proteins of the human immunodeficiency virus (HIV), we summarize our experiences with rapid solid-phase multiple peptide synthesis under low-pressure continuous-flow conditions on standard polystyrene-based resin in a series of concatenated flow reactors with adjustable volume. Alternatively, multiple batchwise synthesis in plastic syringes may be used as a still simpler but a more elaborate procedure. Completeness of acylation of resin-bound free amino groups was monitored by the acid-base indicator bromophenol blue. Efficiency of the coupling reaction was increased by exposure to elevated temperature in an ultrasonic bath. Up to 100 mg of crude peptides were purified on a mass-overloaded Vydac C18 reversed-phase semipreparative HPLC column in one run, this procedure ensuring high recovery of homogeneous peptides. The peptides synthesized were serologically relevant to the detection of anti-HIV-1 antibodies in positive sera.
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PMID:Color-monitored solid-phase multiple peptide synthesis under low-pressure continuous-flow conditions. 213 62

Carbovir is a novel carbocyclic guanosine derivative that has potent in vitro activity against human immunodeficiency virus, the causative agent of acquired immunodeficiency syndrome (AIDS). Two methods of sample preparation were developed for the analysis of carbovir in rat blood. Solid-phase extraction on C18 extraction columns proved to be the most effective. Whole rat blood (200 microliters) was diluted with 0.8 ml of distilled water containing the internal standard. After two freeze-thaw cycles to lyse the red blood cells and subsequent centrifugation at 13,000 g, the supernatant was loaded on the C18 extraction columns. Carbovir and the internal standard were eluted with methanol-water (60:40). The extract was evaporated and reconstituted in mobile phase and the samples were injected onto a high-capacity reversed-phase column. The compounds were detected at 252 nm. Other nucleosides that could be used in the treatment of AIDS such as zidovudine and acyclovir did not interfere. Standard curves were linear over the concentration range 0.156-28.0 micrograms/ml (r2 greater than 0.99). The within-day coefficient of variation was less than 7.6% at all concentrations (n = 4). The between-day coefficient of variation ranged from 16.7 to 2.0% (n = 14). The limit of sensitivity was 0.05 micrograms/ml with a 200-microliters blood sample and the average extraction recovery was 74%. Carbovir was stable in rat blood for at least 4 h at 37 degrees C. The assay was used to determine the blood levels of carbovir in a rat after a 20 mg/kg intravenous dose.
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PMID:Liquid chromatographic assay of carbovir, a carbocyclic nucleoside active against human immunodeficiency virus. 275 56

Lipophilic and hydrophilic extracts of over 900 strains of cultured blue-green algae (cyanophyta) were examined in vitro for their ability to inhibit the reverse transcriptases (RT) of avian myeloblastosis virus (AMV) and human immunodeficiency virus, type 1 (HIV-1). Eighteen (2.0%) aqueous extracts showed activity against AMV and HIV RTs. The maximal level of RT inhibition achieved by some of the active extracts was equivalent to that measured for 3'-azido-2',3'-di-deoxythymidine (AZT) at 668 ng/ml. Examination of partially purified fractions prepared by C18 column chromatography demonstrated that the RT inhibition observed could not be attributed entirely to the degradation of transcript DNA, template RNA, or enzyme protein in the reaction mixture. Thus, these results indicate that cultured blue-green algae may represent a novel source of compounds that inhibit RT activity, including that of HIV-1.
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PMID:Inhibition of reverse transcriptase activity by extracts of cultured blue-green algae (cyanophyta). 768 17

Fibrinogen solutions were irradiated with UVC (254 nm) to inactivate contaminating viruses. In order to protect fibrinogen during UVC irradiation, 0.5 mM rutin was added prior to UVC exposure and subsequently removed during processing. Viral kill by 0.1 J/cm2 UVC resulted in the following inactivation values (log 10): non-lipid-enveloped viruses: Parvo > or = 5.5; encephalomyocarditis virus > or = 6.5; hepatitis A virus > or = 6.5: lipid-enveloped viruses: human immunodeficiency virus > or = 5.7; vesicular stomatitis virus > or = 5.7. Fibrinogen irradiated with 0.5 mM rutin did not significantly differ from unirradiated material in terms of clot time and breaking strength. In the absence of rutin, UVC irradiation of fibrinogen at similar fluence led to loss of solubility, increased clot time and the cleavage of fibrino-peptides that reacted with dinitrophenyl hydrazine as a test for ketonic carbonyl groups. High-performance liquid chromatography and mass spectrometry data showed that rutin exposed to UVC formed numerous breakdown, oxidation and combinational products. Experiments with 3H-rutin showed that after UVC irradiation, subsequent processing by a C18 resin and alcohol precipitation removed > 99% rutin, representing < 10 ppm rutin in the final fibrinogen preparations. Residual 3H-rutin was not covalently bonded to the fibrinogen. Immunochemical studies with rabbit antisera to UVC irradiated (with rutin) fibrinogen showed the absence of neoimmungens. By all measures, rutin prevents fibrinogen degradation during virucidal UVC irradiation.
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PMID:Protecting fibrinogen with rutin during UVC irradiation for viral inactivation. 893 67

A rapid, sensitive and specific high-performance liquid chromatographic (HPLC) assay was developed and validated for the measurement of (-)-2'-deoxy-3'-thiacytidine (3TC) in human serum. The method included precipitation of serum proteins by trichloroacetic acid (20%, w/v) treatment followed by centrifugation. The resulting supernatant was directly injected and 3TC was isocratically chromatographed on a reversed-phase C18 column using a mixture of phosphate buffer and methanol (88.3:11.7. v/v) and monitored at 280 nm. The limit of quantitation was 20 ng/ml using 100 microl of serum. The standard curve was linear within the range of 20-10,000 ng/ml. Replicate analysis of three quality control samples (40-1500 ng/ml) led to satisfactory intra- and inter-assay precision (coefficient of variation from 3.0 to 12.9%) and accuracy (deviation from 6.3 to 9.7%). Moreover, sample treatment processes including human immunodeficiency virus (HIV) heat-inactivation, exposure at room temperature and freezing-thawing cycles did not influence the stability of the analyte. This assay was successfully applied to the determination of 3TC serum levels in HIV-infected patients. In addition, preliminary results indicated that this procedure may also be extended to the measurement of 3TC in human plasma and urine.
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PMID:Rapid quantitation of (-)-2'-deoxy-3'-thiacytidine in human serum by high-performance liquid chromatography with ultraviolet detection. 917 79

We found previously that long-chain fatty acids could inhibit eukaryotic DNA polymerase activities in vitro [1,2]. The purpose of the present study was to investigate the mode of this inhibition in greater detail. Among the C18 to C24 fatty acids examined, the strongest inhibitor was a C24 fatty acid, nervonic acid (NA), and the weakest was a C18 fatty acid, linoleic acid (LA). We analyzed the inhibitory effect of these two fatty acids and their modes of action. For DNA polymerase beta (pol. beta), NA acted by competing with both the substrate- and template-primer, but for DNA polymerase alpha (pol. alpha) or human immunodeficiency virus type 1 reverse transcriptase (HIV-1 reverse transcriptase or HIV-RT), NA acted non-competitively. NA-binding to pol. beta could be stopped with a non-ionic detergent, but the binding to pol. alpha or HIV-RT could not. The inhibition mode of LA showed the same characteristics, except that the minimum inhibitory dose of the longer chain was much lower. We also tested the effects of NA and LA using pol. beta and its proteolytic fragments, as described by Kumar et al. [3,4]. Both of the fatty acids were found to bind to the 8 kDa DNA-binding domain fragment, and to suppress binding to the template-primer DNA. We found that 10,000 times more of either fatty acid was required for it to bind to the 31 kDa catalytic domain or inhibit the DNA polymerase activity. The possible modes of inhibition by these long-chain fatty acids are discussed, based on the present findings.
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PMID:The inhibitory action of fatty acids on DNA polymerase beta. 936 79

A rapid, sensitive and specific high-performance liquid chromatography (HPLC) procedure for the quantification of indinavir, a potent human immunodeficiency virus (HIV) protease inhibitor, in human plasma is described. Following C18 solid-phase extraction, indinavir was chromatographed on a reversed-phase C8 column using a simple binary mobile phase of phosphate buffer-acetonitrile (60:40, v/v). UV detection at 210 nm led to an adequate sensitivity without interference from endogenous matrix components. The limit of quantification was 25 ng/ml with a 0.1 ml plasma sample. The standard curve was linear across the range from 25 to 2500 ng/ml with an average recovery of 91.4%. The mean relative standard deviations for concentrations within the standard curve ranged between 1.4 and 9.7%. Quality control standards gave satisfactory intra- and inter-assay precision (R.S.D. from 3.5 to 15.8%) and accuracy within 15% of the nominal concentration. Sample handling experiments, including HIV heat inactivation, demonstrated analyte stability under expected handling processes. The assay is suitable for the analysis of samples from adult and pediatric patients infected with HIV.
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PMID:Rapid quantification of indinavir in human plasma by high-performance liquid chromatography with ultraviolet detection. 1005 96

The genome of the human immunodeficiency virus type-1 (HIV-1) contains a stretch of approximately 120 nucleotides known as the psi-site that is essential for RNA packaging during virus assembly. These nucleotides have been proposed to form four stem-loops (SL1-SL4) that have both independent and overlapping functions. Stem-loop SL2 is important for efficient recognition and packaging of the full-length, unspliced viral genome, and also contains the major splice-donor site (SD) for mRNA splicing. We have determined the structure of the 19-residue SL2 oligoribonucleotide by heteronuclear NMR methods. The structure is generally consistent with the most recent of two earlier secondary structure predictions, with residues G1-G2-C3-G4 and C6-U7 forming standard Watson Crick base-pairs with self-complementary residues C16-G17-C18-C19 and A12-G13, respectively. However, residue A15, which is located near the center of the stem, does not form a predicted bulge, and residues A5 and U14 do not form an expected Watson-Crick base-pair. Instead, these residues form a novel A5-U14-A15 base-triple that appears to be stabilized by hydrogen bonds from A15-H61 and -H62 to A5-N1 and U14-O2, respectively; from A5-H61 to U14-O2, and from C16-H42 to U14-O2'. A kink in the backbone allows the aromatic rings of the sequential U14-A15 residues to be approximately co-planar, adopting a stable "platform motif" that is structurally similar to the A-A (adenosine) platforms observed in the P4-P6 ribozyme domain of the Tetrahymena group I intron. Platform motifs generally function in RNA by mediating long-range interactions, and it is therefore possible that the A-U-A base-triple platform mediates long-range interactions that either stabilize the psi-RNA or facilitate splicing and/or packaging. Residue G8 of the G8-G9-U10-G11 tetraloop is stacked above the U7-A12 base-pair, and the remaining tetraloop residues are disordered and available for potential interactions with either other RNA or protein components.
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PMID:NMR structure of stem-loop SL2 of the HIV-1 psi RNA packaging signal reveals a novel A-U-A base-triple platform. 1086 Jul 28

A selective assay method for quantitation of amprenavir (agenerase) in human immunodeficiency virus type-1 infected patient serum or plasma using liquid chromatography-tandem mass spectrometry (LC-MS-MS) is described. Amprenavir and an internal standard (reserpine) are extracted by liquid-liquid extraction and chromatographically separated by a reversed-phase C18-analytical column. The triple quadrupole LC-MS-MS system is operated in the positive-ion mode and multiple reaction monitoring is used for drug quantitation. The method has been validated over the range of 0.05-10.0 microg/ml. The RSDs for the intra-day and inter-day determinations ranged from 5.3 to 6.1% and from 4.7 to 6.2%, respectively. The average assay accuracy at two different concentrations ranged from 96.0 to 103.0% and the extraction recovery of amprenavir was 90.8%. The lower limit of quantitation was 0.05 microg/ml. Using a short microbore column, the analysis was completed in less than 5 min.
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PMID:Liquid chromatographic-tandem mass spectrometric determination of amprenavir (agenerase) in serum/plasma of human immunodeficiency virus type-1 infected patients receiving combination antiretroviral therapy. 1135 2


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