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

The macrocyclic polyamines, cyclen and cyclam, and their derivatives have been tested for inhibitory activity against the cytopathogenic effect (CPE) of human immunodeficiency virus type 1 strain HTLV-IIIB (HIV-1IIIB) on CD4+ human lymphoblastoma MT-4 cells. Cyclam and its derivatives were complexed with a variety of transition metal ions NiII, ZnII, CuII, FeIII and CoIII. The divalent metal complexes effected lower toxicity and greater anti-HIV-1 activity, while the trivalent metal complexes had no effect on HIV-1-dependent CPE. When dimerized, the anti-HIV activity of monomers was significantly enhanced. A potent inhibition of CPE by biscyclam was transiently observed 4 d after the virus infection, but was not seen at 6 d due to severe toxicity. The toxicity of biscyclam, referred to as delayed toxicity, could be overcome by a metal complexation. The strain specificities of biscyclams were further studied by testing their effects on syncytium formation between HIV-infected and uninfected human acute lymphoblastic leukemia MOLT-4 cells. The 50% inhibitory concentrations of biscyclams against HIV-2GH-1-dependent syncytium formation were less than one hundredth those for the other HIV strains (HIV-1IIIB, HIV-1RF and HIV-1SF-2).
 ...
PMID:Inhibition of human immunodeficiency virus proliferation by macrocyclic polyamines and their metal complexes. 751 43

Three flavans, daphnodorins A, B and C isolated from Dahpne odora THUNB. were tested for their abilities to inhibit human immunodeficiency virus type 1 (HIV-1(IIIB)) replication in MT-4 cells. The effective concentrations (EC50) of daphnodorins A, B and C against HIV-1-induced cytolysis were 0.26 +/- 0.08, 1.8 +/- 0.6 and 3.6 +/- 0.5 micrograms/ml, respectively. Also these three compounds showed inhibitory effects of p24 antigen in human peripheral blood lymphocytes. As compared with 2',3'-dideoxycytidine 5'-triphosphate (DDC-TP), daphnodorin A and daphnodorin C had relatively weak inhibitory effects on the reverse transcriptase of HIV-1, while daphnodorin B did not show any inhibitory effect at concentrations up to 1000 micrograms/ml. These three compounds showed marked inhibitory effects on syncytium formation between HIV-1(IIIB)-infected and uninfected MOLT-4 (clone 8) cells at 3-30 micrograms/ml without inducing cytotoxicity. The concentrations of the compounds blocking syncytium formation were consistent with the effective concentrations (EC50) against HIV-induced cytolysis of MT-4 cells. These results, differing from reverse transcriptase inhibitors, suggest that the daphnodorins exert their anti-HIV-1 activity through inhibition of early events of viral replication including adsorption of the virions to the cells or the subsequent entry.
 ...
PMID:Inhibition of human immunodeficiency virus type 1 (HIV-1) replication by daphnodorins. 752 15

The goal of this study was to exploit molecular recognition of cell surface receptors by viral surface glycoproteins as a means for the selective intracellular delivery of macromolecules. To accomplish this, artificial viral envelopes (AVE) resembling the human immunodeficiency virus-1 (HIV-1) were designed as a model system. Recombinant HIV-1 surface glycoprotein gp160 (HIV-1 rgp160) was inserted in the artificial envelope by a two-step detergent dialysis process. The artificial HIV-1 envelope recognized the CD4 cell surface receptor. FITC-dextran and ricin A were employed as model macromolecules as they cannot passively diffuse across cell membranes. Selective transfer of FITC-dextran encapsulated in HIV-1 rgp160 AVE into a CD4-positive cell line (REX-1B) versus a CD4-negative cell line (KG-1) was demonstrated. Ricin A at concentrations as low as 2 ng/ml arrested cell growth of CD4-positive MOLT-4 cells, whereas 8 ng/ml ricin A in solution had no effect on cell growth. The arrest of cell growth was reverted in the presence of excess anti-gp120 monoclonal antibody. Naked envelopes (without HIV-1 rgp160 inserted) were also found to interact with cells and transfer material, although less efficiently and in a non-specific manner. Viral mimicry using AVE may be a means for targeted intracellular delivery of peptides, proteins, enzymes, toxins, oligodeoxynucleotides, gene constructs, and other non-diffusive, labile or toxic macromolecules.
 ...
PMID:(Patho)physiologic pathways to drug targeting: artificial viral envelopes. 754 Dec 29

The cell-to-cell transmission of human immunodeficiency virus type 1 (HIV-1) was studied using MOLT-4 cells chronically infected with a variant strain of HIV-1SF-2 (MOLT-4/HIV-1SF-2H) and CD4+ human lymphoid MT-4 cells. MOLT-4/HIV-1SF-2H cells produced less than 1 TCID50 infectious particles per day as determined by the cytopathogenicity in MT-4 cells. However, the expression of envelope glycoproteins gp120 and gp41 on the MOLT-4/HIV-1SF-2H cell membrane was satisfactory for syncytium formation with the uninfected MOLT-4 cells. When MOLT-4/HIV-1SF-2H and MT-4 cells were co-cultured, severe cytopathogenicity was observed in MT-4 cells without being accompanied by the formation of multi-nucleated cells. Thus, the system consisting of MOLT-4/HIV-1SF-2H and MT-4 cells is convenient for exclusive study of the mechanism of cell-to-cell transmission of HIV-1. Using various compounds, it was confirmed that cell-to-cell transmission required both gp120/gp41-CD4 binding and de novo DNA synthesis.
 ...
PMID:Novel assay system favorable for the study of cell-to-cell transmission of HIV-1 and its application to the evaluation of anti-HIV drugs. 755 Jan 35

The in vitro effect of human natural interferon alpha (IFN-alpha) on cell contact-mediated human immunodeficiency virus type 1 (HIV-1) transmission from epithelial cells to lymphocytes was examined. This type of infection is most likely to occur when the mucosal linings of the reproductive or digestive organs serve as latent viral reservoirs and HIV-1 invades the host through the basolateral surface of polarized epithelia upon contact with intraepithelial lymphocytes. The cell-to-cell infection model consisted of target MOLT-4 T lymphocytes exposed for various time periods to chronically HIV-1-infected intestinal monolayers (I407/YH5) in the presence of log10 dilutions of IFN (range 10(5)-10(-2) IU/ml). Concurrent measurements of resulting productive infection from MOLT-4 revealed that complete inhibition of reverse transcriptase activity was prevented by doses starting from 1 IU, whereas the cessation of p24 production occurred at 1000 IU of IFN present at inoculation. The results indicate that IFN can efficiently prevent not only cell-free but also cell-mediated HIV-1 infection--an important means of viral spread in vivo pertinent to HIV-1 transmission resulting from mucosa-lymphocyte interaction.
 ...
PMID:Inhibitory effect of natural interferon alpha on human immunodeficiency virus type 1 transmission from epithelial cells to lymphocytes in vitro. 767 77

Virion infectivity factor (vif), a gene found in all lentiviruses, plays an essential role in virus replication in certain target cells. We examined the replication competence of the human immunodeficiency virus type 2 (HIV-2) vif mutant in different T-cell lines and primary cells in comparison with that of the HIV-1 vif mutant. Both mutant viruses were unable to replicate in peripheral blood-derived mononuclear cells but replicated with wild-type efficiency in certain T-cell lines, such as SupT1 and MOLT-4/8. These results confirm the importance of vif in the infection of relevant target cells and imply that some cellular factor(s) could compensate for vif function. However, HIV-1 and HIV-2 vif mutant viruses also show differential replications in other cell lines, suggesting either different threshold requirements for the same cellular factor(s) or the involvement of different factors to compensate for vif-1 and vif-2 functions. By cross complementation experiments, we showed that vif-1 and vif-2 have similar functions. Our studies further indicate the existence of two kinds of nonpermissive cells: H9 is unable to complement HIV-1 delta vif but is susceptible to a one-round infection with HIV-1 delta vif produced from permissive cells. In contrast, U937 is nonpermissive for HIV-2 delta vif produced from permissive cells but, once infected, is able to complement the delta vif function. In both types of nonpermissive cells, a step prior to proviral DNA synthesis is affected.
 ...
PMID:Comparative analyses of human immunodeficiency virus type 1 (HIV-1) and HIV-2 Vif mutants. 774 2

We have previously shown that lymphocytic cells adhere to cultured syncytiotrophoblast and that this may be important in the lymphocyte-mediated infection of trophoblast with the human immunodeficiency virus (HIV). During the course of studies aimed at investigating the role of cell surface carbohydrates in adhesion, it was discovered that a contaminant of commercial fucose-1-phosphate, dicyclohexylamine, inhibited MOLT-trophoblast adhesion. Dicyclohexylamine and the related compounds, cyclohexylamine and hexylamine, inhibited adhesion in a dose-responsive manner with half-maximal inhibition seen at about 4 mM. While the pressor effects of cyclohexylamine, the principal metabolite of cyclamate, are well known, this is the first report of an effect of this and related compounds on cell adhesion activity. The inhibitory effect was reversible and, at concentrations less than 25 mM, did not result in loss of cell viability. Several possible mechanisms of action of cyclohexylamine were examined in an attempt to explain the effect on adhesion. No evidence was found to suggest that the effects of cyclohexylamine were due to inhibition of polyamine synthesis, increase in intracellular Ca2+ concentration or to a lysosomotropic effect. The concentrations of cyclohexylamine used are within the range of plasma concentrations attainable in humans, raising the possibility that the in vitro effects described here may also occur in vivo. The results also suggest that caution should be used in the interpretation of results obtained from experiments where cell adhesion is blocked using exogenous monosaccharides that are in the form of dicyclohexylammonium salts. Appropriate controls must be included or, if possible, sodium, potassium or barium salts should be chosen.
 ...
PMID:Cyclohexylamine inhibits the adhesion of lymphocytic cells to human syncytiotrophoblast. 776 8

We have previously shown that lymphocytic cells bind to cultured syncytiotrophoblast and that this may be important in the lymphocyte-mediated infection of trophoblast with the human immunodeficiency virus (HIV). Leukocyte-trophoblast adhesion may also have implications for normal trophoblast function. The following experiments were designed to characterize the adhesion systems that mediate the attachment of lymphocytic cells to trophoblast. Adhesion was assayed by labelling lymphocytic MOLT-4, clone 8 cells with the fluorescent marker, calcein-AM, and then incubating them with primary cultures of human syncytiotrophoblast. Adhesion was stimulated by pretreatment of the trophoblast cultures with several cytokines either alone or together. These included tumor necrosis factor-alpha (TNF-alpha), granulocyte/macrophage-colony stimulating factor (GM-CSF), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma). Stimulation was time- and dose-dependent. In contrast, preincubation of trophoblast cultures with anti-TNF-alpha antibodies for 2 days reduced MOLT adhesion by almost 50%. Preincubation with other anti-cytokine antibodies had no significant effect on adhesion. In other experiments, adhesion was measured in the presence of antibodies to known adhesion molecules. Adhesion was reduced by 50% in the presence of antibodies to alpha 4 integrin or beta 1 integrin. When present together, these antibodies reduced adhesion by almost 85%. Incubation in the presence of antibodies to the very late activation antigen-4 (VLA-4; alpha 4 beta 1 integrin) counter-receptors, VCAM-1 and CS-1, was without effect. Adhesion was also unaffected by antibodies to LFA-1, ICAM-1, ICAM-2, LFA-2, or LFA-3. These results suggest that adhesion is mediated by an adhesion system consisting of lymphocyte VLA-4 (alpha 4 beta 1) and an as yet unidentified counter receptor on trophoblast.
 ...
PMID:Effect of cytokines and anti-adhesion molecule antibodies on the adhesion of lymphocytic cells to human syncytiotrophoblast. 780 71

With increasing awareness of the mitochondrial toxicity associated with certain 2',3'-dideoxynucleosides used in anti-human immunodeficiency virus therapy, procedures for quantitative analyses of drug effects on mitochondrial DNA (mtDNA) have assumed enhanced importance. For this reason we have developed a method to measure the copy numbers of mtDNA in cultured MOLT-4 cells. First a hybrid competitive DNA template was synthesized by conventional polymerase chain reaction (PCR), using two custom-synthesized 40-mer composite primers incorporating mitochondrial displacement loop sequences linked by a non-mitochondrial cDNA template (a 76-base pair sequence from the tat/rev region of human immunodeficiency virus cDNA). For the competitive assay, increasing known copy numbers of the hybrid competitive template were added as an internal control to samples containing total cellular DNA. With this approach, two competitive PCR products were generated, 1) a mitochondrial displacement loop-derived fragment (182 base pairs) and 2) a competitive DNA template-derived fragment (156 base pairs). Absolute quantitation was achieved by radiometric comparison of the relative amounts of the two products. To test the versatility of this method, varying amounts of competitive template (6.6 x 10(4) to 6.6 x 10(9) copies) were used with a fixed quantity of total cellular DNA taken from cells cultured for 9 days in the presence or absence of selected pyrimidine and purine dideoxynucleosides. The results showed that the copy number of cellular mtDNA is 823 +/- 71 copies/cell in MOLT-4 cells. Little selective depletion of mtDNA, compared with total cellular DNA, was seen with the purine dideoxynucleosides examined; however, when the cells were exposed to the pyrimidine dideoxynucleoside 2',3'-dideoxycytidine (50 nM) for 9 days, mtDNA content was specifically depleted, although total cellular DNA decreased by only 10%. Thus, in addition to the presently used methods of assessing mitochondrial impairment, i.e., Southern blot analysis and electron microscopy, the competitive PCR method provides a third and convenient assay, with particular applicability to determination of mtDNA in very small numbers of cells.
 ...
PMID:Quantitation of mitochondrial DNA in human lymphoblasts by a competitive polymerase chain reaction method: application to the study of inhibitors of mitochondrial DNA content. 780 25

Tryptase TL2 purified from MOLT-4 human T cells binds to the envelope protein of human immunodeficiency virus type 1 (HIV-1). Tryptase TL2 and CD26 antigen are supposed to play roles in HIV-1 entry into cells. Although CD4 is a principal receptor for HIV-1, brain cells expressing the CD4 antigen are not permissive to HIV-1 strains infectious to monocyte or T-cell lines. We examined whether the non-permissiveness of the brain-derived cells to standard HIV-1 strains could be explained by a lack of tryptase TL2 or CD26. Western blots showed that the amounts of tryptase TL2 expressed in cell lysates prepared from the brain-derived cells were similar to those prepared from various cells susceptible to HIV-1 strains. Furthermore, flow cytometry revealed the presence of the CD26 antigen on the cell surface of many types of cells. The resistance of the brain-derived cells to standard HIV-1 strains is not due to a lack of tryptase TL2 or CD26.
 ...
PMID:Detection of tryptase TL2 and CD26 antigen in brain-derived cells non-permissive to T-cell line-tropic human immunodeficiency virus type 1. 782 28


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>