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)

Fifteen heteropolyoxotungstates were tested for their effects on the proliferation of human immunodeficiency virus type 1 (HIV-1) using an in vitro system consisting of MT-4 cells and HTLV-IIIb. Eight heteropolyoxotungstates (HPOTs) with the Keggin structure or dimerized deficient Keggin structure proved to be potent inhibitors of HIV-1. In contrast, seven non-Keggin HPOTs including HPA 23 did not have significant effects on HIV-1 proliferation at non-toxic doses. [PTi2W10O40]7- (PM-19) was the most potent inhibitor of HIV-1 among the 15 HPOTs tested. The inhibition of HIV-1 replication by PM-19 presumably results from impaired virus adsorption and/or penetration into target cells. Viral spread of HIV-1 and HIV-2 on cell-to-cell basis was also susceptible to PM-19. In combination, PM-19 and 3'-azido-3'-deoxythymidine were synergistic in inhibiting HIV-1 proliferation.
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PMID:Inhibition of proliferation of human immunodeficiency virus type 1 by novel heteropolyoxotungstates in vitro. 185 2

A Keggin polyoxotungstate PM-19 K7[PTi2W10O40].6H2O was found to be a potent inhibitor of the replication of human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS), in OKT4+ cells. In contrast, the effect of HPA 23 (NH4)17Na[NaSb9W21O86], an inhibitor of reverse transcriptase of HIV, was not significant.
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PMID:Inhibition of replication of human immunodeficiency virus by a heteropolyoxotungstate (PM-19). 233 49

We summarize the pathogenesis of animal lentiviruses (visna-maedi virus, caprine arthritis and encephalitis virus, and equine infectious anemia virus), which have raised considerable interest since the discovery of human lentiviruses. The human lentiviruses possess structural, genetic, and clinical properties similar to those of animal lentiviruses. We describe the different mechanisms of and the principal work on reverse transcriptase inhibitors of animal lentiviruses, such as HPA-23, phosphonoformate, or 2',3'-dideoxynucleosides. Animal viruses of this family may serve as models for infection with human lentiviruses such as human immunodeficiency virus, the etiologic agent of AIDS.
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PMID:Animal lentivirus replication and reverse transcriptase inhibitors. 247 76

HPA-23 is a competitive inhibitor of the RNA-dependent DNA polymerase (reverse transcriptase) of the human immunodeficiency virus (HIV). It may therefore potentially benefit patients with HIV infection. This study aimed at defining the haematopoietic toxicity of this drug and particularly its effects on the normal human granulocyte-macrophage progenitor cells (GM-CFU). Our in vitro studies, in semi-solid agar, have shown an inhibitory effect of increasing concentrations of HPA-23 on colony and cluster formation. This effect is probably dose-dependent. An almost complete inhibition of colony formation was observed at doses of more than 20 micrograms/ml. Regarding cluster formation, a similar although much more progressive inhibitory effect was found. Our experimental data should be extrapolated with caution to clinical situations. However, they must be kept in mind for optimal design of HPA-23 therapy in HIV infected patients.
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PMID:Toxicity of HPA-23 (ammonium-21-tungsto-9-antimoniate) for normal human myeloid progenitor cells (GM-CFU) in vitro. 259 Jul 21

The rapid spread of human immunodeficiency virus (HIV) infections and the grim outcome of these infections have focused interest on the possibilities for medical intervention. The end-stage of these infections, acquired immune deficiency syndrome (AIDS), was first recognised in 1981, and the causative agent isolated in 1983. Already several antiviral drugs have been investigated. One initially promising drug, suramin, was found to have a net harmful effect but another, zidovudine (azidothymidine) has been shown to prolong life in AIDS patients. The properties of these and several other antiviral drugs such as antimoniotungstate (HPA-23), foscarnet (phosphonoformate) ribavirin, dideoxynucleotides, and interferons, are reviewed. The role of immunomodulating modalities such as plasmapheresis, bone marrow transplantation, thymosin, interleukin-2, inosine pranobex (isoprinosine), and cyclosporin are also discussed. None of the currently available drugs hold promise as monotherapy. Through analysis of the experience with these drugs and the increasing knowledge of HIV pathogenesis, new drugs can be designed. It seems increasingly clear that drugs will eventually have to be used in combination in order to reduce toxicity, exploit therapeutic synergy, and reduce the risk of HIV resistance. The theoretical and experimental background for such combinations are currently being elucidated.
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PMID:Antiviral therapy in AIDS. Clinical pharmacological properties and therapeutic experience to date. 282 70

Antiviral agents under investigation for the treatment of patients infected with the human immunodeficiency virus (HIV) are reviewed. Multiple mechanisms exist by which antiviral agents might inhibit the replication of HIV or eradicate its latent form in affected cells, or both. These mechanisms include (1) interference with the cell surface receptor for HIV, (2) prevention of uncoating of viral particles, (3) inhibition of reverse transcriptase, (4) prevention of integration and posttranscription processing, (5) interference with viral assembly, and (6) interference with virus release. Most agents developed thus far work by inhibiting HIV reverse transcriptase. Suramin, ribavirin, ammonium 21-tungsten-9-antimoniate (HPA-23), foscarnet (phosphonoformate, PFA), inosine pranobex (isoprinosine), peptide T, ampligen, AL 721, dideoxycytidine, and zidovudine (formerly azidothymidine) have antiretroviral activity in vitro. To date zidovudine is the only antiretroviral agent approved by the FDA as clinically effective. However, zidovudine has serious toxicities, including neutropenia and anemia; in some patients dosage reduction or cessation of therapy may be necessary. Because treatment with zidovudine does not cure HIV infection, numerous studies are under way with other anti-HIV agents. Ultimately, combinations of agents probably will be used to suppress or eradicate HIV. While the search for more efficacious and less toxic treatments continues, the development of zidovudine in such a short time provides hope that progress toward a cure will be made rapidly.
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PMID:Development of antiviral agents for the treatment of human immunodeficiency virus infection. 332 38

Effective antiviral drugs are urgently needed to treat individuals who are infected with the human immunodeficiency virus (HIV). Several compounds, such as nucleoside analogs (AZT, ddCyd), phosphonoformate, and HPA-23 inhibit reverse transcriptase. The mode of action of ribavirin and interferon alpha A is less clear. A number of compounds have been tested in early clinical trials, and AZT so far looks the most promising. New drugs should undergo rapid but thorough in vitro and animal testing. Promising compounds should be made available as soon as possible for phase I trials.
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PMID:Treatment of human immunodeficiency virus infections. 333 93

The current epidemic of acquired immunodeficiency syndrome (AIDS) poses a major threat to our population. Urgently needed are both a vaccine to prevent infection with the etiologic retrovirus, human immunodeficiency virus (HIV), and safe, effective antiviral agents to treat those individuals already infected. The elucidation of viral replicative mechanisms has allowed the development and testing of several agents active against HIV in vitro. Inhibitors of reverse transcriptase that have demonstrated activity include azidothymidine, phosphonoformate, antimoniotungstate (HPA-23), and suramin. Ribavirin and recombinant interferon alpha-A (IFN-alpha-A) also inhibit HIV replication, although their mechanisms of action are less clear. All of these compounds are undergoing early clinical trials in patients with HIV infection. The identification of immunogenic viral proteins may allow the development of one or more subunit vaccines against HIV. Studies are underway to clone appropriate viral genes and incorporate the expressed proteins into vectors for administration. Laboratory models, e.g., chimpanzees, will be inoculated with candidate vaccines and, if successful, this will be followed by clinical trials for safety and efficacy in appropriate human populations seronegative for HIV. Although important problems, such as virus envelope protein variability, need to be addressed, efforts to develop effective vaccines may well prove successful in the years ahead.
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PMID:Prospects for the prevention and therapy of infections with the human immunodeficiency virus. 354 Nov 31

Using the protein A haemolytic plaque assay (PrA-HPA) and standardized, optimal conditions, pokeweed mitogen (PWM) stimulated peripheral blood lymphocytes (PBL) from normal donors produced 5,500-48,000 (mean 16,955) IgG plaque-forming cells (PFC) per 10(6) lymphocytes, 3,375-38,000 (mean 14,179) IgA-PFC/10(6) and 5,500-69,750 (mean 18,684) IgM-PFC/10(6). Addition of 4 micrograms/ml concanavalin A (Con A) at the start of PWM stimulation of PBL from normal donors gave 59-98% (mean 84%) suppression of IgG-PFC, 46-99% (mean 79%) suppression of IgA-PFC and 31-100% (mean 82%) suppression of IgM-PFC. When PFC/10(6) values in PWM-stimulated co-cultures of unfractionated PBL from pairs of unrelated normal donors were compared with PFC/10(6) obtained in the individual PWM-stimulated cultures, observed/expected ratios were between 0.81 and 1.24 (mean 0.99) for IgG-PFC, 0.85 and 1.23 (mean 0.98) for IgA-PFC and 0.86 and 1.25 (mean 1.03) for IgM-PFC. Cord blood lymphocytes (CBL) produced few PWM-stimulated PFC and co-culture of CBL with normal PBL gave markedly reduced observed/expected ratios, indicating hyperactivity of T-suppressor cells in cord blood. PBL from a patient with partial DiGeorge syndrome also responded poorly in the PWM-driven PrA-HPA, but co-culture of this patient's PBL with normal PBL and PWM gave rise to higher than expected values, indicating reduced T-helper cell function. These simple methods could be employed in clinical evaluation of the cellular defect in humoral immunodeficiency and autoimmune disease states.
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PMID:Clinical evaluation of B cell and T-regulator cell function using a protein A haemolytic plaque assay. 646 53

Interactions between HPA (Hypothalamic-pituitary-axis) and immune system seem to involve the EPO (endogenous opioid peptides) system, as shown by some recent findings. Possible relationships between beta-endorphin (beta-End) synthesis and severity rate of immunodeficiency have been studied in 48 HIV Ab positive patients, at different stages of infection. A statistically significant decrease in the beta-End synthesis was observed in these patients, as compared to a control group of 19 healthy subjects, but this decrease was not related to the CD4+T lymphocytes number. Plasmatic levels modifications of HPA-related peptides were not observed in the IVC1 CDC group.
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PMID:Beta-endorphins ACTH and cortisol in CSF and plasma of HIV infected patients. 876 83


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