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)

We examined the inhibitory activities of 10 polyether antibiotics on human immunodeficiency virus (HIV) type 1. These compounds caused concentration-dependent inhibition of HIV replication in primary infected cultures of human T-lymphoblastoid H9 cells. The ratio of 50% effective concentrations for cellular cytotoxicity (MTT assay) to antiviral activity (reverse transcriptase assay) was over 5. Anti-HIV activity was also observed in cultures of monocytic lineage U937 cells chronically infected with HIV.
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PMID:Inhibitory effects of polyethers on human immunodeficiency virus replication. 160 20

A rapid and sensitive procedure was developed for in vitro evaluation of anti-herpes simplex virus (HSV) agents. The procedure is based on spectrophotometrical assessment for viability of virus- and mock-infected cells via in situ reduction of a tetrazolium dye MTT, which has already been used for the detection of anti-human immunodeficiency virus (HIV) agents (Pauwels et al., 1988). Monolayer cells such as human embryonic fibroblast, VERO, or HeLa cells were not suitable for this purpose. Among the non-adherent cell lines examined for susceptibility to HSV type 1 (HSV-1), a B-lymphoblastoid cell line NC-37 was found to be the most sensitive. The cell line was found to have a good correlation between the viable cell number and the reduction of MTT. In addition, centrifugation of the virus-infected cells resulted in further increase of the sensitivity of NC-37 cells to HSV-1. After optimization, the method proved to be as sensitive as plaque reduction. The system simplifies significantly the assay procedures and thus permits the evaluation of larger numbers of compounds for anti-HSV-1 activity.
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PMID:An application of tetrazolium (MTT) colorimetric assay for the screening of anti-herpes simplex virus compounds. 165 29

Sera were obtained from 50 individuals infected with human immunodeficiency virus type 1 or from HIV-1-uninfected individuals before or after vaccination with recombinant gp160. These sera were evaluated for activity antagonistic to the cell-killing activity of the chimeric Pseudomonas exotoxin hybrid protein, sCD4-PE40. For these studies, Chinese hamster ovary (CHO) cells were transfected with a chimeric plasmid encoding the tat, rev, and envelope genes of HIV-1 and a cell line was selected for stable expression of the envelope glycoproteins at the cell surface (CHO-env). Cytotoxicity of sCD4-PE40 for CHO-env in the presence or absence of added human serum was quantitated spectrophometrically following enzymatic reduction of a tetrazolium bromide within the mitochondria of viable cells (MTT assay). Several HIV+ sera inhibited the cytotoxic activity of sCD4-PE40; the antagonist had properties consistent with those of immunoglobulins in that it was heat stable, absorbed by protein A, and reversible by increasing the concentration of sCD4-PE40. Of 15 HIV+ sera which strongly reacted with gp120, 11 (73%) also potently inhibited sCD4-PE40 cytotoxicity, and cytotoxicity was inhibited by sera from some HIV- individuals after, but not before, immunization with gp160. These data suggested a role for antibody to gp120 in the antagonistic activity. However, not all sera with antibody to gp120 antagonized sCD4-PE40 cytotoxicity and high levels of antagonist activity were frequently (40%) found in HIV+ sera lacking immunoblot-detectable antibody to gp120, or antibody to either CD4 or PE40. Grouping of the HIV+ sera according to the patients' absolute number of CD4+ cells revealed that the degree of inhibition of sCD4-PE40 cytotoxicity approached a Gaussian distribution, suggesting that persons with CD4+ cell counts between 200 and 700/mm3 may be more likely to possess significant levels of serum antagonist. This data have implications for the clinical development of sCD4-PE40 or other sCD4-based therapeutics in the management of HIV-1 infection.
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PMID:Soluble CD4-PE40 is cytotoxic for a transfected mammalian cell line stably expressing the envelope protein of human immunodeficiency virus (HIV-1), and cytotoxicity is variably inhibited by the sera of HIV-1-infected patients. 174 81

The inactivation of human immunodeficiency virus (HIV) and cytotoxic properties of ozone-treated serum and serum-supplemented media were examined. The titer of HIV suspensions in human serum was reduced in a dose-dependent manner when treated with total reacted ozone concentrations at a range of 0.5 to 3.5 micrograms/ml-1. Complete inactivation of HIV suspensions was achieved by 4.0 micrograms/ml-1 of ozone in the presence or absence of H-9 cells. In contrast, cellular metabolism, as measured by MTT dye cleavage, and DNA replication, as measured by BUdR incorporation, were enhanced in H-9 cells grown in media treated with quantities of ozone that completely inactivate HIV. The permissively HIV-infected cell line HXB/H-9 was cultured in ozone-treated media for six days with culture supernatants being sampled and assayed on alternate days for HIV p24 core protein. HIV p24 was reduced in all treated cultures compared to control cultures, with an average reduction of 46% [p24].
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PMID:Ozone inactivates HIV at noncytotoxic concentrations. 180 86

(R)- And (S)-8-aza-9(-)[2-(phosphonomethoxy)propyl]guanine [(R)-and (S)-8-aza-PMPG] were synthesized and tested in vitro for anti-human immunodeficiency virus (HIV) activity. The synthesis of the above compounds and of (R)-9(-)[2-(phosphonomethoxy)propyl]guanine [(R)-PMPG] was carried out through the alkylation of 8-azaguanine or guanine with (R)- and (S)-2-O(-)[(diisopropylphosphono)methyl]-1-O-(tolylsulfonyl) -1,2-propanediol followed by deprotection of the phosphonic moiety. A different, even more convenient synthesis of (R)-8-aza-PMPG starting from 2-amino-6-chloro-5-nitro-4(3H)-pyrimidinone and (R)(-)[2(-)[(diisopropylphosphono)-methoxy]propyl]amine is also reported. Both (R)-8-aza-PMPG and (R)-PMPG demonstrated anti-HIV activity in the MTT assay with EC50 values of 12 and 4.5 microM, respectively. The corresponding S enantiomers were found to be less potent. When evaluated in combination with AZT, ddI, or DABO 603, (R)-8-aza-PMPG gave additive, additive, and synergistic anti-HIV-1 effects, respectively.
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PMID:Synthesis and antiviral activity of 8-aza analogs of chiral [2-(phosphonomethoxy) propyl]guanines. 756 35

By using ELISA and assay of MTT participating in IL-6 dependent cell clone. The authors measured the circulating levels of soluble IL-2 receptor (sIL-2R) and IL-6 in patients undergoing hemodialysis (HD). Alterations of the above-mentioned parameters before and after a three-month course of treatment with Chinese drug Epimedium sagittatum on the same HD patients. It is confirmed that in patients with end-stage renal failure (ESRF), sIL-2R level elevated significantly, while IL-6 level decreased apparently (P < 0.01). Furthermore, levels of both sIL-2R and IL-6 could be restored to normal after treatment with Epimedium sagittatum. These findings indicated not only the presence of immunodeficiency in ESRF, but also the effectiveness of regulation with Chinese drug Epimedium sagittatum.
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PMID:[Effect of epimedium sagittatum on soluble IL-2 receptor and IL-6 levels in patients undergoing hemodialysis]. 779 53

5'-Modified pentadecadeoxyribonucleotides with a sequence (5'-TGGGAGGTGGGTCTG-3') (15mer) complimentary (antisense) to the tat 2nd splicing acceptor region of human immunodeficiency virus type 1 (HIV-1) were prepared and evaluated for anti-HIV-1 activity. The modified antisense oligodeoxyribonucleotides (AS-ODNs) were synthesized using 5'-modified thymidine 3'-phosphoramidites as the 5'-terminal residues. The structures of the 5'-modified 15mers were confirmed by negative ion LSI mass spectroscopy, and the anti-HIV-1 activities were evaluated in vitro by the MTT assay using MT-4 cells. While the unmodified 15mer had no activity in our assay system, the 15mers bearing modifications with trityl-type substituents at the 5'-end showed high anti-HIV-1 activities.
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PMID:Biologically active oligodeoxyribonucleotides--I: Syntheses and anti-HIV-1 activities of 5'-modified pentadecadeoxyribonucleotides. 824 95

Seven 2',3'-dideoxynucleosides synthesized by substitution of nucleosides using nucleoside deoxyribosyltransferase from Lactobacillus leichmanii were tested for their anti-human immunodeficiency virus (HIV) activity. Two of them, including 2,6-diaminopurine-2',3'-dideoxyriboside (DAPDDR) and 6-chlorpurine-2',3'-dideoxyriboside (CPDDR) demonstrated high antiviral activity against several strains of HIV-1 and one strain of HIV-2. The selectivity index of the drugs (SI; ratio of the drug concentration required for 50% of cell killing to drug concentration required to inhibit 50% of virus-induced cell killing) was established by application of tetrazolium (MTT) colorimetric assay. SI ranged for different HIV strains from 501 to 850 and from 60 to 118 for DAPDDR and CPDDR, respectively. Both DAPDDR and CPDDR retained their antiviral activity against HIV-1 strain D148/88 which was resistant to Zidovudine (3'-azido-3'-deoxythymidine, AZT). Assays for clonal growth of human bone marrow cells in semisolid fibrin clot culture medium demonstrated that DAPDDR possesses significantly lower inhibitory activity for erythroid (BFU-E), multipotent (GEMM-CFC) and granulocyte-monocyte (GM-CFC) bone marrow progenitor cells than CPDDR or AZT. These results suggest that DAPDDR is a nucleoside analog which should be further tested as an anti-HIV compound especially in combination with other anti-retroviral drugs.
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PMID:In vitro anti-human immunodeficiency virus activity of 2',3'-dideoxynucleosides and their effect on clonal growth of hemopoietic cells from human bone marrow. 832 11

Previously, we described two mutants of the cellular Rev co-factor, eukaryotic initiation factor 5A (eIF-5A M13 and M14), which suppress human immunodeficiency virus type 1 (HIV-1) SF2 replication in clonal T cell lines. This study introduced the notion that it is possible to develop gene therapies against infectious agents on the basis of mutant host factors required for viral replication. In this report, we provide further evidence to support this new paradigm and describe murine leukemia virus (MLV)-based retroviral vectors expressing three different eIF-5A mutants from the viral long terminal repeat (LTR). HIV-1 replication (SF2, HXB-3) was reduced up to 2 orders of magnitude in transduced, polyclonal T cell populations. All eIF-5A mutants also showed antiviral activity (approximately seven-fold reduction) in a chronic HIV-1 infection model. Expression of eIF-5A mutant M13 delta in peripheral blood lymphocytes (PBLs) showed no difference in proliferation and metabolic activity as determined in a 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT)-assay, suggesting that expression of this type of mutant protein is not associated with cellular toxicity. In summary, these data suggest that gene therapy for HIV-1 infection can be developed on the basis of mutants of the Rev co-factor eIF-5A.
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PMID:Intracellular expression of cellular eIF-5A mutants inhibits HIV-1 replication in human T cells: a feasibility study. 889 78

Superoxide dismutase (SOD) is an enzyme used in the treatment of oxygen radical-related diseases. Lecithinization of SOD enhances its pharmacological activity. Lecithinized SOD (PC-SOD) inhibits human immunodeficiency virus (HIV) types 1 and 2 in MT-4 cells. HIV-1-infected MT-4 cells were cultured for 5 days in the presence of PC-SOD, at various concentrations. In an MTT assay, reverse transcriptase (RT) activity of the cell extract and p24 antigen production were measured. Untreated, HIV-1-infected MT-4 cells served as control. PC-SOD inhibited viral replication most effectively at 2500 U/ml, a concentration that did not affect cell viability, with an EC50 value of 718 U/ml. PC-SOD treatment inhibited RT activity and p24 production in a dose-dependent manner. Western blot analysis of the HIV-1-infected MT-4 cells treated with PC-SOD at 2500 U/ml did not detect any expression of viral proteins. Failure to inhibit virus adsorption, proviral DNA and mRNA synthesis, and RT and proteinase enzyme activity suggests that the mechanism of action of PC-SOD is entirely different from those of the currently available anti-HIV drugs. PC-SOD shows synergistic interaction with AZT, ddI, ddC, KNI-272, and dextran sulfate. PC-SOD also inhibited the oxidative stress-induced depletion of sulfhydryls, which are the cause of diminished antioxidant defenses in HIV-infected patients.
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PMID:Lecithinized superoxide dismutase: an inhibitor of human immunodeficiency virus replication. 907 27


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