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)

Pokeweed antiviral protein (PAP), a 29-kDa protein isolated from Phytolacca americana inhibits translation by catalytically removing a specific adenine residue from the 28S rRNA of eukaryotic ribosomes. PAP has potent antiviral activity against many plant and animal viruses, including human immunodeficiency virus. We describe here development of a positive selection system to isolate PAP mutants with reduced toxicity. In vitro translation in the presence or absence of microsomal membranes shows that PAP is synthesized as a precursor and undergoes at least two different proteolytic processing steps to generate mature PAP. The PAP cDNA was placed under control of the galactose-inducible GAL1 promoter and transformed into Saccharomyces cerevisiae. Induction of PAP expression was lethal to yeast. The PAP expression plasmid was mutagenized and plasmids encoding mutant PAP genes were identified by their failure to kill S. cerevisiae. A number of mutant alleles were sequenced. In one mutant, a point mutation at Glu-177 inactivated enzymatic function in vitro, suggesting that this glutamic acid residue is located at or near the catalytic site. Mutants with either point mutations near the N terminus or a nonsense mutation at residue 237 produced protein that was enzymatically active in vitro, suggesting that the toxicity of PAP is not due solely to enzymatic activity. Toxicity of PAP appears to be a multistep process that involves possibly different domains of the protein.
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PMID:Isolation and characterization of pokeweed antiviral protein mutations in Saccharomyces cerevisiae: identification of residues important for toxicity. 766 9

Envelope glycoproteins of human immunodeficiency virus (gp120 and gp41) occur as oligomers. Here, we show by gel filtration analysis that gp120 oligomerization in vitro is calcium- and temperature-dependent. Recombinant gp120 (rgp120) species were recovered as monomers at 20 degrees C in the absence of calcium, but as tetramers at 37 degrees C in 10 mM CaCl2. Under the latter condition, N-glycanase-deglycosylated rgp120 formed hexamers. Relative to intact rgp120, which has been reported to display carbohydrate-binding properties for N-acetyl-beta-D-glucosaminyl and mannosyl residues, deglycosylation enhanced rgp120 specific binding to mannose-divinylsulfone-agarose, para-aminophenyl-beta-D-GlcNAc-agarose and fetuin-agarose matrices. Taken together, these results rule out the role of homologous lectin-carbohydrate interactions via N-linked glycans in the rgp120 oligomerization, even though its lectin properties may also be calcium-dependent. Deglycosylation may unmask domains of rgp120 polypeptide backbone that independently play a role either in rgp120 lectin activity or in calcium-dependent oligomerization.
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PMID:The role of calcium and N-linked glycans in the oligomerization and carbohydrate binding properties of human immunodeficiency virus external envelope glycoprotein. 780 9

The mucin-type carbohydrate Tn cryptantigen (GalNAc alpha 1-O-Ser/Thr, where GalNAc is N-acetyl-D-galactosamine) is expressed in many carcinomas, in haemopoietic disorders including the Tn syndrome, and on human immunodeficiency virus (HIV) coat glycoproteins, but is not expressed on normal, differentiated cells because of the expression of a Tn-processing galactosyltransferase. Using Jurkat T leukaemic cells which express high levels of Tn antigen due to deficient Tn galactosylation, we have established the Tn antigen-mediated gene transfer and demonstrate the considerable efficiency of this approach. We used poly(L-lysine) conjugates of the monoclonal antibody 1E3 directed against the Tn antigen to deliver the luciferase and beta-galactosidase reporter genes to Jurkat cells by receptor-mediated endocytosis. Addition of unconjugated 1E3 reduced transfection efficiency in a concentration-dependent manner and incubation with free GalNAc abolished DNA transfer completely, indicating that gene delivery is indeed mediated by the Tn antigen. Pre-treatment of Jurkat cells with Vibrio cholerae sialidase, which uncovers additional Tn antigens, resulted in an improvement of gene transfection. Both human and chicken adenovirus particles attached to the DNA/polylysine complex strongly augmented transgene expression. When the beta-galactosidase (lacZ) gene was delivered to Jurkat cells by Tn-mediated endocytosis, up to 60% of the cells were positive in the cytochemical stain using 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) as a chromogenic substrate. The efficiency of the transferrin receptor-mediated DNA uptake into Jurkat cells was comparatively low, although these cells were shown to express considerable amounts of transferrin receptor. We show here that a mucin-type carbohydrate antigen mediates highly efficient DNA uptake by endocytosis into Jurkat T cells. This method represents a 50-fold improvement of Jurkat cell transfection efficiency over other physical gene transfer techniques. Specific gene delivery to primary cancer cells exhibiting Tn epitopes may especially be desirable in immunotherapy protocols.
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PMID:Carbohydrate receptor-mediated gene transfer to human T leukaemic cells. 782 4

The glycosylation pattern of the external envelope glycoprotein of human immunodeficiency virus type 2 (HIV-2) was studied in dependence on host cells and virus isolates. Strains HIV-2ALT, HIV-2ROD and HIV-2D194, differing in their biological properties and in the amino acid sequences of their env genes, were propagated in MOLT4, HUT78 and U937 cells, in human peripheral blood lymphocytes and monocytes/macrophages in the presence of [6-3H]glucosamine. Radiolabelled viral glycoproteins were isolated from the cell-free supernatants and digested with trypsin. Glycans were sequentially liberated by endo-beta-N-acetylglucosaminidase H and peptide-N4-(N-acetyl-beta-glucosaminyl) asparagine amidase F, and fractionated according to charge and size. Comparison of the oligosaccharide profiles revealed that the envelope glycoproteins of different virus isolates, propagated in the same host cells, yielded very similar glycan patterns, whereas cultivation of an isolate in different host cells resulted in markedly divergent oligosaccharide maps. Variations concerned the proportion of high-mannose-, hybrid- and complex-type substituents, as well as the state of charge and structural parameters of the complex-type species. As a characteristic feature, complex-type glycans of macrophage-derived viral glycoprotein were almost exclusively substituted by lactosamine repeats. Hence, glycosylation of the HIV-2 external envelope glycoprotein seems to be primarily governed by host cell-specific factors rather than by the amino acid sequence of the corresponding polypeptide backbone.
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PMID:Oligosaccharide profiles of HIV-2 external envelope glycoprotein: dependence on host cells and virus isolates. 782 9

The intercellular adhesion molecule (ICAM-1, CD54) and its counter receptor, the integrin leukocyte function associated antigen 1 (LFA-1, CD11a/CD18), have important roles in the immune response. These include guiding leukocytes to sites of inflammation (Issekutz and Issekutz, 1992), enhancement of antigen presentation (Moy and Brian, 1992) and potentiation of cytotoxic cell function (Umehara et al., 1992; Sanchez-Madrid et al., 1982). In addition to these activities LFA-1 and ICAM-1 are implicated in the cell-to-cell transmission of human immunodeficiency virus (HIV-1) since antibodies to CD18, CD54 or synthetic peptide analogs of ICAM-1 antagonise the formation of virus-induced syncytia (Fecondo et al., 1993; Gruber et al., 1991; Hildreth and Orentas, 1989; Valentin et al., 1990). The alpha-glucosidase 1 inhibitor 6-O-butanoyl castanospermine (MDL 28574) has antiviral activity for HIV which is manifested by a decrease in syncytia as well as the production of virus with altered gp120 and a reduced infectivity (Taylor et al., 1991). Previously, it has been shown that the alpha-glucose 1 inhibitor (MDL 28574) treatment of human leukocytes in vitro or mouse lymphocytes in vivo affects the detection of LFA-1 but not domain 1 of CD4 nor several other CD markers (Bridges et al., submitted for publication). Here, we demonstrate that pre-treatment of HIV-permissive CD4+ cells with MDL 28574 substantially reduces their capacity to bind with cells chronically infected with HIV-1 which results in reduced virus production.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The prevention of cell adhesion and the cell-to-cell spread of HIV-1 in vitro by the alpha-glucosidase 1 inhibitor, 6-O-butanoyl castanospermine (MDL 28574). 784 78

The Orchidaceae species Listera ovata and Epipactis helleborine contain two types of mannose-binding proteins. Using a combination of affinity chromatography on mannose-Sepharose-4B and ion exchange chromatography on a Mono-S column eight different mannose-binding proteins were isolated from the leaves of Listera ovata. Whereas seven of these mannose-binding proteins have agglutination activity and occur as dimers composed of lectin subunits of 11-13 kDa, the eighth mannose-binding protein is a monomer of 14 kDa devoid of agglutination activity. Moreover, the monomeric mannose-binding protein does not react with an antiserum raised against the dimeric lectin and, in contrast to the lectins, is completely inactive when tested for antiretroviral activity against human immunodeficiency virus type 1 and type 2. Mannose-binding proteins with similar properties were also found in the leaves of Epipactis helleborine. However, in contrast to Listera only one lectin was found in Epipactis. Despite the obvious differences in molecular structure and biological activities molecular cloning of different mannose-binding proteins from Listera and Epipactis has shown that these proteins are related and some parts of the sequences show a high degree of sequence homology indicating that they have been conserved through evolution.
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PMID:The monomeric and dimeric mannose-binding proteins from the Orchidaceae species Listera ovata and Epipactis helleborine: sequence homologies and differences in biological activities. 787 28

Cryptococcal meningitis is an uncommon infection globally, including Nigeria. This systemic fungal infection often is associated with immunodeficiency. The most common causes of meningitis in Nigeria in the 2-3 year age group are the malaria parasites and bacteria. The concomitant infections of Cryptococcal neoformans and Plasmodium falciparum are uncommon. We present here the report of a case of fatal cryptococcal meningitis with malaria infection in a 2 year old child from Nigeria (one of the malaria endemic regions of the world). This case emphasizes the importance of doing a combination of fungal and bacterial cultures as well as looking for malarial parasites in the determination of etiological agents of meningitis in any hospital in Africa. We suggest that cerebrospinal fluid from meningitis cases must be cultured using Sabouraud dextrose agar and any growth on the agar must be examined using Indian ink.
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PMID:Cryptococcal meningitis with malaria. A case report. 793 35

Staphylococcal strains can release a factor that strongly activates the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in THP-1 cells transfected with the HIV-1 LTR-driven luciferase reporter gene (THP-1 LTRluc). The factor is present in the overnight culture fluid and is readily released from the organisms into aqueous medium by vigorous mixing. Staphylococcal extracellular material is a complex mixture of polysaccharide and protein containing peptidoglycan and teichoic acid, released in part by cell wall turnover. The importance of the carbohydrate component is emphasized by concanavalin A (Con A) inhibition of staphylococcal product-induced LTR activation but not of activation by phorbol 12-myristate 13-acetate or tumor necrosis factor. The effect of Con A was decreased or abolished by sugars in the order methyl alpha-D-mannopyranoside > methyl alpha-D-glucopyranoside > mannose > glucose = fructose > N-acetylglucosamine. Wheat germ agglutinin was less inhibitory than Con A; in this instance N-acetylglucosamine decreased inhibition, whereas methyl alpha-D-mannopyranoside or methyl alpha-D-glucopyranoside did not. The induction of luciferase activity in THP-1 LTRluc by the staphylococcal extracellular product also was inhibited by fetal bovine and normal human serum. A comparison of 31 staphylococcal isolates (9 Staphylococcus aureus, 11 Staphylococcus epidermidis, 2 Staphylococcus haemolyticus, 4 Staphylococcus hominis, 2 Staphylococcus capitis, 2 Staphylococcus warneri, 1 Staphylococcus saprophyticus) revealed wide variation in LTR activating activity that did not correlate closely with slime production. Our findings, using induction of luciferase in THP-1 LTRluc as a model for upregulation of HIV infection, raise the possibility that staphylococci, as well as certain other microorganisms, release carbohydrate-containing exopolymers, which can activate the HIV-1 LTR, thus influencing progression of HIV infection.
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PMID:Activation of the human immunodeficiency virus long terminal repeat in THP-1 cells by a staphylococcal extracellular product. 793 1

The effects of some triterpenoid saponins on glucose transport in Ehrlich ascites tumor (EAT) cells were examined by measuring 2-deoxy-D-glucose (2-DG) uptake. The correlation of the effects with those on the growth of a human T-cell line (MT-4) and the replication of human immunodeficiency virus in MT-4 cells was also studied. Chikusetsusaponin Ia isolated from rhizomes of Panax japonicus C. A. Meyer (Araliaceae) inhibited the 2-DG uptake (IC50 = 76.3 microM) in a competitive fashion with respect to 2-DG (Ki = 0.32 mM) and the growth of MT-4 cells with CC50 of 84.4 microM, whereas it did not show any significant anti-HIV-1 activity. In contrast, zingibroside R1 isolated from rhizomes of Panax zingiberensis Wu et Feng (Araliaceae) showed some anti-HIV-1 activity, which was found to be superior to that of glycyrrhizin, as well as the inhibitory effects on the 2-DG uptake by EAT cells (IC50 = 91.3 microM) and the growth of MT-4 cells (CC50 = 46.2 microM).
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PMID:Inhibitory effect of some triterpenoid saponins on glucose transport in tumor cells and its application to in vitro cytotoxic and antiviral activities. 807 91

We reviewed the charts of 52 patients infected with human immunodeficiency virus (HIV) who received at least three consecutive doses of intravenous pentamidine as prophylaxis for Pneumocystis carinii infections. Pentamidine isethionate was administered intravenously over 60-90 minutes once a month, at a dosage of 4 mg/kg, in 250 mL of 5% dextrose in water. During 387 months of administration of primary prophylaxis to 37 patients, no cases of P. carinii pneumonia were observed. During 200 months of administration of secondary prophylaxis to 15 patients, only one case of P. carinii pneumonia was diagnosed (6.0 cases per 100 patient-years). Side effects associated with the intravenous pentamidine were mild and did not necessitate withdrawal of the drug. Once-a-month administration of intravenous pentamidine is a valid alternative as prophylaxis for P. carinii pneumonia for patients who are intolerant of sulfonamides.
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PMID:Once-a-month administration of intravenous pentamidine to patients infected with human immunodeficiency virus as prophylaxis for Pneumocystis carinii pneumonia. 808 50


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