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 attempted to select monoclonal antibodies (mAb) which reacted with T-cell surface molecules and were able to interfere with the human immunodeficiency virus type 1 (HIV1) replicative cycle in the MT4 T-leukaemic cell line. In comparison with OKT4A, an anti-CD4 mAb, only one mAb, HC11.151.1, was found to significantly delay HIV-induced cytopathic effect on MT4 cells among the 15 mAb tested which reacted with MT4 cell surface antigens. Biochemical and immunological characterization of HC11.151.1 demonstrated its specificity for beta 2-microglobulin (beta 2m), the light chain of human leukocyte antigen (HLA) class I molecules. Other beta 2m-specific mAb were tested in order to assess whether this effect represented an intrinsic capacity of HC11.151.1 or whether it was a common feature shared by all anti-beta 2m mAb. Three (B1.1G6, B2.62.2 and BBM1) of the four anti-beta 2m mAb demonstrated the same protective effect, whereas C21.48A, which was devoid of a functional effect, was directed towards a beta 2m epitope involved in binding to the HLA class I heavy chain molecule. The physiological relevance of this observation is discussed.
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PMID:Anti-beta 2-microglobulin monoclonal antibodies mediate a delay in HIV1 cytopathic effect on MT4 cells. 226 10

Novel synthetic sulfated polymers, namely, sulfated polyvinyl alcohol (PVAS) and sulfated copolymers of acrylic acid with vinyl alcohol (PAVAS), proved to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) and HIV-2 in vitro. The compounds completely inhibited HIV-1-induced cytopathogenicity in MT-4 cells and HIV-1 antigen expression in CEM cells at a concentration of 0.8 micrograms/ml. They were equally effective against HIV-2 replication. In addition, and in contrast to azidothymidine, PAVAS and PVAS suppressed HIV-1-induced giant cell (syncytium) formation, a process that may account for the depletion of T4 lymphocytes in patients with acquired immunodeficiency syndrome. PAVAS and PVAS completely blocked giant cell formation at a concentration of 4 micrograms/ml, whereas for dextran sulfate a concentration of 100 micrograms/ml was required to achieve complete inhibition of giant cell formation. As has been demonstrated previously for the sulfated polysaccharides, the mechanism of action of PAVAS and PVAS resides in the inhibition of virus adsorption to the cells.
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PMID:Novel sulfated polymers as highly potent and selective inhibitors of human immunodeficiency virus replication and giant cell formation. 232 49

In view of the selective anti-HIV activity of 2',3'-dideoxy-3'-fluoro-5-chlorouridine (11), a series of eight 2',3'-dideoxy-5-chloropyrimidines were synthesized and evaluated for their inhibitory activity against human immunodeficiency virus type 1 (HIV-1) replication in MT-4 cells. A marked improvement in selectivity was noted for the 5-chlorouracil derivatives of 2,3-dideoxyribofuranose, 3-azido-2,3-dideoxyribofuranose, and 3-fluoro-2,3-dideoxyribofuranose, mainly due to decreased toxicity of the compounds for the host cells. While chlorination of 2',3'-dideoxycytidine removed the anti-HIV activity, introduction of a chlorine at the C-5 position of 3'-fluoro-, 3'-azido- or 2',3'-didehydro-2',3'-dideoxycytidine led to reduced cytotoxicity with only slightly reduced anti-HIV activity. X-ray analysis showed compound 11 to have two molecules in the asymmetric unit with chi = -168.8 (3) degrees and -131.3 (3) degrees and P = 179 (1) degree and 163 (1) degree, respectively; thus revealing no close resemblance to 3'-azido-3'-deoxythymidine (AZT).
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PMID:Synthesis and anti-HIV evaluation of 2',3'-dideoxyribo-5-chloropyrimidine analogues: reduced toxicity of 5-chlorinated 2',3'-dideoxynucleosides. 234 78

The production of tumor necrosis factor (TNF)-alpha and TNF-beta by various human hematopoietic cell lines was quantitatively examined using a highly sensitive radioimmunoassay specific to TNF-alpha, or a cytolytic assay performed with mouse L929 cells. It was found that the HTLV-1-infected T cell lines examined produced large amounts of both TNF-alpha and TNF-beta. In particular, interleukin-2 (IL-2)-dependent cell lines produced large amounts of TNF-alpha. In contrast, human cell lines not infected with HTLV-1 essentially did not produce either of the TNFs. It was also found that the high production of TNF-alpha by HTLV-1-infected cells partially correlated to their high sensitivity to human immunodeficiency virus (HIV) infection. Treatment of MT-4 cells, one of the most HIV-sensitive HTLV-1-infected cell lines, with antibody specific to TNF-alpha reduced their sensitivity to HIV infection.
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PMID:Production of tumor necrosis factors by human T cell lines infected with HTLV-1 may cause their high susceptibility to human immunodeficiency virus infection. 235 83

Different treatment schedules have been investigated when evaluating the inhibitory effect of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and 3'-azido-2',3'-dideoxythymidine (AZT) on the replication of human immunodeficiency virus type I (HIV-I) in MT-4 cells, transformation of C3H/3T3 cells by Moloney murine sarcoma virus (MSV), and MSV-induced tumor formation in newborn NMRI mice. Shortening the exposure time of HIV-I-infected MT-4 cells to PMEA or AZT led to an increase in the selectivity index of both compounds. PMEA proved markedly more efficient in suppressing MSV-induced tumor formation in mice when administered as a single dose on the day of infection than when these doses were spread over 2, 4 or 7 administrations within 1 week after the virus infection. This was not observed when the total dose of AZT was fractionated. While the infrequent dosage regimen increased the anti-retrovirus activity of PMEA, it did not increase its toxicity for the host. This unique property makes PMEA an attractive candidate for the treatment of retrovirus infections, including AIDS.
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PMID:Anti-retrovirus activity of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) in vivo increases when it is less frequently administered. 238 80

Novel sulfated polysaccharides, sulfated bacterial glycosaminoglycan (Org 31581) and chemically degraded heparin (Org 31733), have proved to be potent and selective inhibitors of human immunodeficiency virus (HIV) in vitro. Their 50% inhibitory concentrations for HIV type 1 (HIV-1) in MT-4 cells were 0.67 and 0.52 micrograms/ml, respectively. These values are comparable to those obtained for dextran sulfate and standard heparin (0.39 and 0.89 micrograms/ml, respectively). Org 31581 and Org 31733 showed much less antithrombin activity than did dextran sulfate and standard heparin. These results indicate that the anti-HIV activity of sulfated polysaccharides can be dissociated from their antithrombin activity. Org 31581 and Org 31733 were equally inhibitory to HIV-2 and HIV-1 and were also inhibitory to the replication of human cytomegalovirus. Syncytium formation, induced by cocultivation of MOLT-4 (clone 8) cells with chronically HIV-1-infected HuT 78 cells, was also inhibited by Org 31581. As previously demonstrated with dextran sulfate and heparin, both Org 31581 and Org 31733 blocked virus adsorption to the host cells. These compounds offer great promise as candidate drugs for the chemotherapy of HIV infections.
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PMID:Novel sulfated polysaccharides: dissociation of anti-human immunodeficiency virus activity from antithrombin activity. 240 68

The inhibitory effect of all-trans-retinoic acid (RA) on human immunodeficiency virus (HIV) replication upon infection was studied quantitatively using a novel bioassay system with a HTLV-I-carrying human T-cell line, MT-4. The results can be summarized as follows. The appearance of HIV antigen was significantly reduced when the cells were treated with more than 1 microgram/ml of the chemical after infection. When HIV specific plaque assay was performed to titrate the virus from the supernatant of culture treated with 10 micrograms/ml of RA no plaques were observed. When RA was applied directly in the plaque assay, significant decrease of the number of plaques was discerned showing 68, 66, 47 and 16, at doses of 0.1, 1, 5, and 10 micrograms/ml of RA, while 102 plaques were formed in the control dish. The appearance of cytopathic effects of MT-4 cells by HIV was more delayed in RA-treated cultures than in untreated cultures. Concomitant treatment of the cells with 5 micrograms/ml of RA and various concentrations of suramin resulted in the more effective inhibition of HIV replication than suramin alone. RA did not inhibit the reverse transcriptase activity (RT) of HIV directly. These data suggest that RA inhibits HIV replication by inducing an antiviral state in the cells.
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PMID:Effect of retinoic acid on the replication of human immunodeficiency virus in HTLV-I-positive MT-4 cells. 244 Dec 39

Glycyrrhizin sulfate (GLS) was synthesized and investigated for antiviral effect on the human immunodeficiency virus (HIV) in vitro in comparison with the parental anti-HIV compound glycyrrhizin (GL). In MT-4 cells after HIV infection, the virus-induced cytopathic effect and the expression of viral antigens were inhibited by 0.25 mg/ml (0.184 mM) of GLS. Moreover, GLS completely inhibited HIV-induced plaque formation in MT-4 cells at a concentration of 1 mg/ml (736 microM), the 50% inhibitory dose being 0.055 mg/ml (40 microM). GLS was found to be an efficient inhibitor of reverse transcriptase. The effect of GLS was 4 times stronger than that of GL in molar terms.
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PMID:A new anti-human immunodeficiency virus substance, glycyrrhizin sulfate; endowment of glycyrrhizin with reverse transcriptase-inhibitory activity by chemical modification. 244 73

The polyanionic substances dextran sulfate and heparin were investigated for their antiviral effect on the human immunodeficiency virus (HIV) in vitro. Dextran sulfate and heparin effected a 50% reduction in the cytopathogenicity of HIV for MT-4 cells at a concentration of 4.7 and 7.5 micrograms/ml, respectively. In Molt-4 (clone 8) cells, these values were slightly higher (14.1 and 15.6 micrograms/ml, respectively). No toxicity for the host cells was noted with these compounds at a concentration up to 400 micrograms/ml, so that the selectivity indexes, as based on the ratio of the 50% cytotoxic dose to the 50% antiviral effective dose, were well in excess of 100. These findings may have far reaching implications both diagnostically, when attempts are made to isolate HIV from heparinized blood samples, as therapeutically, to the extent that dextran sulfate or heparin may be useful in blocking HIV replication in vivo.
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PMID:Inhibitory effect of dextran sulfate and heparin on the replication of human immunodeficiency virus (HIV) in vitro. 244 84

The inhibitory effects of several polysaccharides, dextran, xylofuranan, and ribofuranan, and their sulfated counterparts on the infectivity and replication of human immunodeficiency virus (HIV) were examined by using an HTLV-I-carrying cell line, MT-4, in vitro. Dextran sulfate (Mw 34 X 10(3], xylofuranan sulfate, and ribofuranan sulfate completely prevented HIV-induced cytopathic effects (CPE) at concentrations greater than 10 micrograms/ml and dextran sulfate (Mw 7 X 10(3] at concentrations greater than 100 micrograms/ml. However, the non-sulfated compounds did not prevent them at any concentration tested. The anti-HIV effect of these polysaccharides was confirmed by measuring HIV-specific antigen expression in infected MT-4 cells. In cocultures with MOLT-4 and MOLT-4/HIVHTLV-IIIB cells, formation of multinucleated cells was completely inhibited in the presence of 100 micrograms/ml of these sulfated compounds. Dextran sulfate showed 20-30% growth inhibition of uninfected MT-4 cells at 1000 micrograms/ml but dextran sulfate, xylofuranan sulfate, and ribofuranan sulfate showed no effect on sulfated polysaccharides efficiently inhibited the reverse transcriptase activity of avian myeloblastosis virus and HIV.
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PMID:Sulfation of polysaccharides generates potent and selective inhibitors of human immunodeficiency virus infection and replication in vitro. 244 45


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