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)

The effect of 44 different metal ions (Ag+, Al3+, As(O-)2, Au3+, Ba2+, Be2+, Bi3+, Cd2+, Ce3+, CO2+, Cr(O2-)4, Cr3+, Cs+, Cu2+, Fe3+, Fe2+, Ga3+, Ge4+, Hg2+, Ir4+, La3+, Li+, Mn2+, MO6+, Ni2+, OS4+, Pb2+, Pt4+, Rb+, Rh3+, Sb5+, Se(O2-)4, Se(O2-)3, Sn2+, Sr2+, Th4+, T1+, U(O2+)2, V(O-)3, VO2+, W(O2-)4, Y3+, Zn2+, and Zr4+) on the activity of the reverse transcriptase (RT) of the human immunodeficiency virus (HIV-1) was investigated in vitro. For this study, the RT activity assay was carried out by means of an enzyme-linked immunosorbent assay (ELISA) kit, using the template/primer hybrid poly(A) oligo(dT)15, which required some modifications: (1) possible interfering metal chelators (such as EDTA) in the original lysis buffer were avoided, and a new buffer (50 mM Tris-NO3, pH 7.8) was used throughout; (2) an amount of 2 ng of RT per well was considered to be optimal after checking the linearity of the reaction with increasing amounts of enzyme; (3) an incubation temperature of 37 degrees C and an incubation time of 1 h were chosen after preliminary studies in a wide range of temperature and time. At an incubation temperature > or = 40 degrees C, there was a dramatic loss of enzymatic activity. In addition, when RT alone was preincubated for 1 h at 5 degrees C, 25 degrees C, and 37 degrees C, there was a large (83%) loss of activity at 37 C as compared to that at 5 degrees C. These results are indicative of enzyme thermolability, which is higher in the absence of substrates. The effect of metal ions on RT activity was tested using two different metal salt concentrations (10(-4) M and 10(-5) M). Under such experimental conditions, the presence of five metal ions (Pt4+, Ag+, Rh3+, Zn2+, and Hg2+) decreased the RT activity in a dose-response fashion. The observed order of effectiveness with respect to inhibition was Pt4+ > Ag+ > Rh3+ > Zn2+ = Hg2+. Estimated mean inhibitory concentrations (IC50) were 7.8 microM for (NH4)2PtCl6, 14.1 microM for AgNO3, 46.8 microM for RhCl3, 53.7 microM for Zn(SO)4, and 56.2 microM for Hg(NO3)2. Because these data are of the same order of magnitude as the corresponding values related to other RT inhibitors used in anti-AIDS therapy, metal compounds or their derivatives could give an interesting contribution in the development of new RT inhibitors for clinical use.
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PMID:Effects of trace metal compounds on HIV-1 reverse transcriptase: an in vitro study. 1032 22

The receptor for human T-cell leukemia virus type 1 (HTLV-1) was found to be expressed on a broad range of cell lines derived from multiple species. Receptor expression was assessed using human immunodeficiency virus type 1 particles, pseudotyped with the HTLV-1 envelope glycoprotein, and expressing luciferase under the control of an SV40 enhancer and promoter. Infection by pseudotyped virus was blocked with neutralizing antibodies to HTLV-1, and infection was dependent on the presence of the cleavage and fusogenic sequences in the envelope protein precursor. Trypsin treatment of susceptible target lymphocytes reduced entry. Entry was partially resistant to ammonium chloride.
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PMID:The HTLV receptor is a widely expressed protein. 1068 25

Since the Marburg (MBG) and Ebola (EBO) viruses have sequence homology and cause similar diseases, we hypothesized that they associate with target cells by similar mechanisms. Pseudotype viruses prepared with a luciferase-containing human immunodeficiency virus type 1 backbone and packaged by the MBG virus or the Zaire subtype EBO virus glycoproteins (GP) mediated infection of a comparable wide range of mammalian cell types, and both were inhibited by ammonium chloride. In contrast, they exhibited differential sensitivities to treatment of target cells with tunicamycin, endoglycosidase H, or protease (pronase). Therefore, while they exhibit certain functional similarities, the MBG and EBO virus GP interact with target cells by distinct processes.
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PMID:Distinct mechanisms of entry by envelope glycoproteins of Marburg and Ebola (Zaire) viruses. 1077 38

From the roots of the Chinese ginseng Panax ginseng a protein designated panaxagin with ribonuclease activity, but possessing a sequence distinct from ribonucleases previously reported from ginseng calluses, was isolated. The purification protocol employed comprised extraction with cold saline, (NH4)2SO4 precipitation, ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on SP-Sepharose, and gel filtration on Superdex 75 by fast protein liquid chromatography. The purified protein was composed of two identical subunits each with a molecular weight of 26 kDa. Its N-terminal amino acid sequence exhibits sites of similarity with the sequences of plant ribosome inactivating proteins and fungal ribonucleases. The spectrum of biological activities of panaxagin encompassed ribonuclease activity toward yeast transfer RNA, translation-inhibitory activity in a rabbit reticulocyte lysate system, and antifungal activity against fungi including Coprinus comatus and Fusarium oxysporum, but not against Rhizoctonia solani. In addition it displayed an inhibitory activity against human immunodeficiency virus reverse transcriptase and succinylation augmented this activity.
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PMID:Panaxagin, a new protein from Chinese ginseng possesses anti-fungal, anti-viral, translation-inhibiting and ribonuclease activities. 1120 66

Recent observations demonstrated that the antimalarial drug chloroquine (CQ) can kill the opportunistic fungus Cryptococcus neoformans. Since CQ blunts lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha release, it was hypothesized that this drug would also interfere with the inflammatory response to C. neoformans and Candida albicans, another fungal opportunist. CQ inhibited TNF-alpha release from peripheral blood mononuclear cells from healthy and human immunodeficiency virus-positive donors without affecting NF-kappaB activation. CQ reduced TNF-alpha mRNA levels by a pH-dependent mechanism in a manner similar to 2 unrelated alkalizing drugs (ammonium chloride and bafilomycin), which also inhibited TNF-alpha gene expression. Although CQ inhibited release of interleukin (IL)-1beta and IL-6, it did not affect IL-10 or macrophage inflammatory protein-1alpha production. Thus, CQ interferes with fungus-induced TNF-alpha expression by a mechanism that probably depends on the alkalization of endolysosomes. This contrasts with CQ's reported pH-independent inhibition of LPS-stimulated TNF-alpha release and suggests that the mechanism of CQ's anti-inflammatory effects is stimulus specific.
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PMID:Chloroquine antagonizes the proinflammatory cytokine response to opportunistic fungi by alkalizing the fungal phagolysosome. 1123 11

The antimicrobial activities of chloroquine (CQ) and several 4-aminoquinoline drugs were tested against Penicillium marneffei, an opportunistic fungus that invades and grows inside macrophages and causes disseminated infection in AIDS patients. Human THP1 and mouse J774 macrophages were infected in vitro with P. marneffei conidia and treated with different doses of drugs for 24 to 48 h followed by cell lysis and the counting of P. marneffei CFU. CQ and amodiaquine exerted a dose-dependent inhibition of fungal growth, whereas quinine and artemisinin were fungistatic and not fungicidal. The antifungal activity of CQ was not due to an impairment of fungal iron acquisition in that it was not reversed by the addition of iron nitrilotriacetate, FeCl3, or iron ammonium citrate. Perl's staining indicated that CQ did not alter the ability of J774 cells to acquire iron from the medium. Most likely, CQ's antifungal activity is due to an increase in the intravacuolar pH and a disruption of pH-dependent metabolic processes. Indeed, we demonstrate that (i) bafilomycin A1 and ammonium chloride, two agents known to alkalinize intracellular vesicles by different mechanisms, were inhibitory as well and (ii) a newly synthesized 4-amino-7-chloroquinoline molecule (compound 9), lacking the terminal amino side chain of CQ that assists in drug accumulation, did not inhibit P. marneffei growth. These results suggest that CQ has a potential for use in prophylaxis of P. marneffei infections in human immunodeficiency virus-infected patients in countries where P. marneffei is endemic.
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PMID:Inhibition of intramacrophage growth of Penicillium marneffei by 4-aminoquinolines. 1130 9

A mannose-binding lectin was isolated from the inner shoots of the chive Allium tuberosum. The procedure involved aqueous extraction, (NH4)2SO4 precipitation, dialysis to remove (NH4)2SO4, affinity chromatography on mannose-agarose, ion exchange chromatography on SP-Sepharose, gel filtration on Superdex 75, and ion exchange chromatography on Mono S. Lectin activity was adsorbed on mannose-agarose, SP-Sepharose, and Mono S. The lectin demonstrated a molecular weight of 13 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration, indicating that it is a single-chain protein. N-terminal sequence analysis revealed its remarkable homology to Allium cepa lectin and similarity to a lesser extent to lectins from members of the Amaryllidaceae, Orchidaceae, and Liliaceae. The lectin manifested mitogenic activity in murine splenocytes and inhibitory activity against human immunodeficiency virus type 1 reverse transcriptase.
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PMID:A monomeric mannose-binding lectin from inner shoots of the edible chive (Allium tuberosum). 1173 87

A total of 61 strains of Staphylococcus aureus and 177 coagulase-negative staphylococcal strains were isolated from the blood of patients with bloodstream infections and from the skin of both children under cancer treatment and human immunodeficiency virus-positive patients. The MIC analyses revealed that 118 isolates (50%) were resistant to quaternary ammonium compound-based disinfectant benzalkonium chloride (BC). The frequencies of resistance to a range of antibiotics were significantly higher among BC-resistant staphylococci than among BC-sensitive staphylococci. Of 78 BC-resistant staphylococcal isolates, plasmid DNA from 65 (83%), 2 (3%), 43 (55%), and 15 (19%) isolates hybridized to qacA or -B (qacA/B), qacC, blaZ, and tetK probes, respectively. The qacA/B and blaZ probes hybridized to the same plasmid in 19 (24%) staphylococcal strains. The plasmids harboring both qacA/B and blaZ genes varied from approximately 20 to 40 kb. The Staphylococcus epidermidis Fol62 isolate, harboring multiresistance plasmid pMS62, contained qacA/B and blaZ together with tetK. Molecular and genetic studies indicated different structural arrangements of blaZ and qacA/B, including variable intergenic distances and transcriptional directions of the two genes on the same plasmid within the strains. The different organizations may be due to the presence of various genetic elements involved in cointegration, recombination, and rearrangements. These results indicate that qac resistance genes are common and that linkage between resistance to disinfectants and penicillin resistance occurs frequently in clinical isolates in Norway. Moreover, the higher frequency of antibiotic resistance among BC-resistant strains indicates that the presence of either resistance determinant selects for the other during antimicrobial therapy and disinfection in hospitals.
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PMID:Frequency of disinfectant resistance genes and genetic linkage with beta-lactamase transposon Tn552 among clinical staphylococci. 1218 31

Productive entry of human immunodeficiency virus type 1 (HIV-1) into a host cell is believed to proceed via fusion of the viral envelope with the host cell's plasma membrane. Interestingly, the majority of HIV-1 particles that bind to the cell surface are taken up by the host cell via endocytosis; however, this mode of internalization generally does not result in infection. Presumably, virus particles remain trapped in the endocytic pathway and are eventually degraded. Here, we demonstrate that treatment of cells with various pharmacological agents known to elevate the pH of endosomes and lysosomes allows HIV-1 to efficiently enter and infect the host cell. Pretreatment of cells with bafilomycin A1 results in up to a 50-fold increase in the infectivity of HIV-1(SF2). Similarly, pretreatment of target cells with amantadine, concanamycin A, concanamycin B, chloroquine, and ammonium chloride resulted in increases in HIV-1 infectivity ranging between 2- and 15-fold. Analysis of receptor and coreceptor expression, HIV-long terminal repeat (LTR) transactivation, and transduction with amphotropic-pseudotyped murine leukemia virus (MLV)-based vectors suggests that the increase in infectivity is not artifactual. The increased infectivity under these conditions appears to be due to the ability of HIV-1 and MLV particles to enter via the endocytic pathway when spared from degradation in the late endosomes and lysosomes. These results could have significant implications for the administration of current and future lysosmotropic agents to patients with HIV disease.
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PMID:Inhibition of endosomal/lysosomal degradation increases the infectivity of human immunodeficiency virus. 1238 5

Ribavirin in combination with alpha 2 interferon is the consensus treatment for chronic hepatitis C. However, recent preliminary pharmacological studies have suggested that the bioavailability of ribavirin displays great interindividual variability. In order to monitor serum ribavirin levels during combination treatment, we developed and validated a quantitative assay using an approach adaptable for routine hospital laboratories. The method involved solid-phase extraction on phenyl boronic acid cartridges followed by high-performance liquid chromatography with a C(18)-bonded silica column and a mobile phase containing 10 mM ammonium phosphate buffer (with the pH adjusted to 2.5) and UV detection (207 nm). The sensitivity, recovery, linearity of the calibration curve, intra- and interassay accuracies, precision, and stability at 4 degrees C were consistent with its use in the laboratory routine. In addition, other nucleoside analogues sometimes used with ribavirin in patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus did not interfere with the quantification of ribavirin levels. The ribavirin concentration was quantified in 24 serum samples from patients with chronic hepatitis C treated with a combination of ribavirin and alpha 2 interferon. The mean serum ribavirin concentration was 2.67 +/- 1.06 micro g/ml (n = 24) at week 12 of treatment (W12) and 3.24 +/- 1.35 micro g/ml (n = 24) at week 24 of treatment (W24). In addition, ribavirin concentrations displayed high interindividual variabilities: the coefficients of variation of the serum ribavirin concentrations adjusted to the administered dose were 44 and 48% at W12 and W24, respectively. Moreover, the ribavirin concentration was higher in patients with a sustained virological response (n = 11) than in patients with treatment failure (n = 13), with significant intergroup differences at W12 (P = 0.030) and W24 (P = 0.049). The present study describes a simple analytical method for the quantification of ribavirin in human serum that could be a useful tool for the monitoring of ribavirin concentrations in HCV-infected patients in order to improve the efficacy and safety of therapy with ribavirin plus interferon.
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PMID:Ribavirin quantification in combination treatment of chronic hepatitis C. 1249 79


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