Sample records for neutralizing anti-human immunodeficiency

  1. Comprehensive Cross-Clade Neutralization Analysis of a Panel of Anti-Human Immunodeficiency Virus Type 1 Monoclonal Antibodies

    PubMed Central

    Binley, James M.; Wrin, Terri; Korber, Bette; Zwick, Michael B.; Wang, Meng; Chappey, Colombe; Stiegler, Gabriela; Kunert, Renate; Zolla-Pazner, Susan; Katinger, Hermann; Petropoulos, Christos J.; Burton, Dennis R.

    2004-01-01

    Broadly neutralizing monoclonal antibodies (MAbs) are potentially important tools in human immunodeficiency virus type 1 (HIV-1) vaccine design. A few rare MAbs have been intensively studied, but we still have a limited appreciation of their neutralization breadth. Using a pseudovirus assay, we evaluated MAbs from clade B-infected donors and a clade B HIV+ plasma against 93 viruses from diverse backgrounds. Anti-gp120 MAbs exhibited greater activity against clade B than non-B viruses, whereas anti-gp41 MAbs exhibited broad interclade activity. Unexpectedly, MAb 4E10 (directed against the C terminus of the gp41 ectodomain) neutralized all 90 viruses with moderate potency. MAb 2F5 (directed against an epitope adjacent to that of 4E10) neutralized 67% of isolates, but none from clade C. Anti-gp120 MAb b12 (directed against an epitope overlapping the CD4 binding site) neutralized 50% of viruses, including some from almost every clade. 2G12 (directed against a high-mannose epitope on gp120) neutralized 41% of the viruses, but none from clades C or E. MAbs to the gp120 V3 loop, including 447-52D, neutralized a subset of clade B viruses (up to 45%) but infrequently neutralized other clades (?7%). MAbs b6 (directed against the CD4 binding site) and X5 (directed against a CD4-induced epitope of gp120) neutralized only sensitive primary clade B viruses. The HIV+ plasma neutralized 70% of the viruses, including some from all major clades. Further analysis revealed five neutralizing immunotypes that were somewhat associated with clades. As well as the significance for vaccine design, our data have implications for passive-immunization studies in countries where clade C viruses are common, given that only MAbs b12 and 4E10 were effective against viruses from this clade. PMID:15542675

  2. Induction of anti-human immunodeficiency virus (HIV) neutralizing antibodies in rabbits immunized with recombinant HIV--hepatitis B surface antigen particles.

    PubMed Central

    Michel, M L; Mancini, M; Sobczak, E; Favier, V; Guetard, D; Bahraoui, E M; Tiollais, P

    1988-01-01

    Fragments of the human immunodeficiency virus (HIV) envelope coding region have been fused with the hepatitis B virus envelope middle protein. In this system, HIV antigenic determinants are exposed at the surface of a highly antigenic structure, the hepatitis B surface antigen particle. Immunization of rabbits with these particles elicited antibodies directed against both parts of the hybrid protein. One of the rabbit antisera not only exhibited a neutralizing effect on the original HIV1 isolate but also on a divergent Zairian isolate. The HIV sequence in this recombinant is 84 amino acids long and contains conserved and variable domains and a region critical for interaction with the CD4 receptor. Such recombinant antigens could be primary elements in the design of a polyvalent vaccine. Images PMID:2460859

  3. Identification and Characterization of a Peptide That Specifically Binds the Human, Broadly Neutralizing Anti-Human Immunodeficiency Virus Type 1 Antibody b12

    PubMed Central

    Zwick, Michael B.; Bonnycastle, Lori L. C.; Menendez, Alfredo; Irving, Melita B.; Barbas, Carlos F.; Parren, Paul W. H. I.; Burton, Dennis R.; Scott, Jamie K.

    2001-01-01

    Human monoclonal antibody (MAb) b12 recognizes a conformational epitope that overlaps the CD-4-binding site of the human immunodeficiency virus type 1 (HIV-1) envelope. MAb b12 neutralizes a broad range of HIV-1 primary isolates and protects against primary virus challenge in animal models. We report here the discovery and characterization of B2.1, a peptide that binds specifically to MAb b12. B2.1 was selected from a phage-displayed peptide library by using immunoglobulin G1 b12 as the selecting agent. The peptide is a homodimer whose activity depends on an intact disulfide bridge joining its polypeptide chains. Competition studies with gp120 indicate that B2.1 occupies the b12 antigen-binding site. The affinity of b12 for B2.1 depends on the form in which the peptide is presented; b12 binds best to the homodimer as a recombinant polypeptide fused to the phage coat. Originally, b12 was isolated from a phage-displayed Fab library constructed from the bone marrow of an HIV-1-infected donor. The B2.1 peptide is highly specific for b12 since it selected only phage bearing b12 Fab from this large and diverse antibody library. PMID:11413337

  4. The Broadly Neutralizing Anti-Human Immunodeficiency Virus Type 1 4E10 Monoclonal Antibody Is Better Adapted to Membrane-Bound Epitope Recognition and Blocking than 2F5? †

    PubMed Central

    Huarte, Nerea; Lorizate, Maier; Maeso, Rubén; Kunert, Renate; Arranz, Rocio; Valpuesta, José M.; Nieva, José L.

    2008-01-01

    The broadly neutralizing 2F5 and 4E10 monoclonal antibodies (MAbs) recognize epitopes within the membrane-proximal external region (MPER) that connects the human immunodeficiency virus type 1 (HIV-1) envelope gp41 ectodomain with the transmembrane anchor. By adopting different conformations that stably insert into the virion external membrane interface, such as helical structures, a conserved aromatic-rich sequence within the MPER is thought to participate in HIV-1-cell fusion. Recent experimental evidence suggests that the neutralizing activity of 2F5 and 4E10 might correlate with the MAbs' capacity to recognize epitopes inserted into the viral membrane, thereby impairing MPER fusogenic activity. To gain new insights into the molecular mechanism underlying viral neutralization by these antibodies, we have compared the capacities of 2F5 and 4E10 to block the membrane-disorganizing activity of MPER peptides inserted into the surface bilayer of solution-diffusing unilamellar vesicles. Both MAbs inhibited leakage of vesicular aqueous contents (membrane permeabilization) and intervesicular lipid mixing (membrane fusion) promoted by MPER-derived peptides. Thus, our data support the idea that antibody binding to a membrane-inserted epitope may interfere with the function of the MPER during gp41-induced fusion. Antibody insertion into a cholesterol-containing, uncharged virion-like membrane is mediated by specific epitope recognition, and moreover, partitioning-coupled folding into a helix reduces the efficiency of 2F5 MAb binding to its epitope in the membrane. We conclude that the capacity to interfere with the membrane activity of conserved MPER sequences is best correlated with the broad neutralization of the 4E10 MAb. PMID:18596094

  5. The Long Third Complementarity-Determining Region of the Heavy Chain Is Important in the Activity of the Broadly Neutralizing Anti-Human Immunodeficiency Virus Type 1 Antibody 2F5

    PubMed Central

    Zwick, Michael B.; Komori, H. Kiyomi; Stanfield, Robyn L.; Church, Sarah; Wang, Meng; Parren, Paul W. H. I.; Kunert, Renate; Katinger, Hermann; Wilson, Ian A.; Burton, Dennis R.

    2004-01-01

    The human monoclonal antibody 2F5 neutralizes primary human immunodeficiency virus type 1 (HIV-1) with rare breadth and potency. A crystal structure of a complex of 2F5 and a peptide corresponding to its core epitope on gp41, ELDKWAS, revealed that the peptide interacts with residues at the base of the unusually long (22-residue) third complementarity-determining region of the heavy chain (CDR H3) but not the apex. Here, we perform alanine-scanning mutagenesis across CDR H3 and make additional substitutions of selected residues to map the paratope of Fab 2F5. Substitution of residues from the base of the H3 loop or from CDRs H1, H2, and L3, which are proximal to the peptide, significantly diminished the affinity of Fab 2F5 for gp41 and a short peptide containing the 2F5 core motif. However, nonconservative substitutions to a phenylalanine residue at the apex of the H3 loop also markedly decreased 2F5 binding to both gp41 and the peptide, suggesting that recognition of the core epitope is crucially dependent on features at the apex of the H3 loop. Furthermore, substitution at the apex of the H3 loop had an even more pronounced effect on the neutralizing activity of 2F5 against three sensitive HIV-1. These observations present a challenge to vaccine strategies based on peptide mimics of the linear epitope. PMID:14990736

  6. The long third complementarity-determining region of the heavy chain is important in the activity of the broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2F5.

    PubMed

    Zwick, Michael B; Komori, H Kiyomi; Stanfield, Robyn L; Church, Sarah; Wang, Meng; Parren, Paul W H I; Kunert, Renate; Katinger, Hermann; Wilson, Ian A; Burton, Dennis R

    2004-03-01

    The human monoclonal antibody 2F5 neutralizes primary human immunodeficiency virus type 1 (HIV-1) with rare breadth and potency. A crystal structure of a complex of 2F5 and a peptide corresponding to its core epitope on gp41, ELDKWAS, revealed that the peptide interacts with residues at the base of the unusually long (22-residue) third complementarity-determining region of the heavy chain (CDR H3) but not the apex. Here, we perform alanine-scanning mutagenesis across CDR H3 and make additional substitutions of selected residues to map the paratope of Fab 2F5. Substitution of residues from the base of the H3 loop or from CDRs H1, H2, and L3, which are proximal to the peptide, significantly diminished the affinity of Fab 2F5 for gp41 and a short peptide containing the 2F5 core motif. However, nonconservative substitutions to a phenylalanine residue at the apex of the H3 loop also markedly decreased 2F5 binding to both gp41 and the peptide, suggesting that recognition of the core epitope is crucially dependent on features at the apex of the H3 loop. Furthermore, substitution at the apex of the H3 loop had an even more pronounced effect on the neutralizing activity of 2F5 against three sensitive HIV-1. These observations present a challenge to vaccine strategies based on peptide mimics of the linear epitope. PMID:14990736

  7. Candidate Sulfonated and Sulfated Topical Microbicides: Comparison of Anti-Human Immunodeficiency Virus Activities and Mechanisms of Action

    Microsoft Academic Search

    Irini A. Scordi-Bello; Arevik Mosoian; Cejiang He; Yiban Chen; Yang Cheng; Gary A. Jarvis; Marla J. Keller; Kathleen Hogarty; Donald P. Waller; Albert T. Profy; Betsy C. Herold; Mary E. Klotman

    2005-01-01

    Poly(styrene 4-sulfonate), cellulose sulfate, polymethylenehydroquinone, and PRO 2000 are sulfated or sulfonated polymers (SPs) under development as topical microbicides. They are presumed to work through similar mechanisms of action, although to date there has been no extensive comparison of their anti-human immunodeficiency virus activities. To determine whether any of these candidate microbicides offers a potential advantage, their in vitro activities,

  8. Anti-human immunodeficiency virus type 1 humoral immune response and highly active antiretroviral treatment.

    PubMed

    Bongertz, Vera; Ouverney, E Priscilla; Fernandez, Saada Chequer; Grinsztejn, Beatriz; Veloso, Valdilea; Couto-Fernandez, José C; Pilotto, José H; Morgado, Mariza G

    2007-11-01

    Highly active antiretroviral treatment (HAART) of human immunodeficiency type 1 (HIV-1) infection is very effective in controlling infection, but elimination of viral infection has not been achieved as yet, and upon treatment interruption an immediate rebound of viremia is observed. A combination of HAART with an immune stimulation might allow treatment interruption without this rebounding viremia, as the very low viremias observed with successful HAART may be insufficient to permit maintenance of a specific anti-HIV-1 immune response. The objective of this study was to compare the humoral immune response of individuals undergoing successful HAART (NF=no failure) with that of individuals with evidence of failure of therapy (FT) and to verify if the viremia peaks observed in individuals with therapy failure would act as a specific stimulus for the humoral anti-HIV-1 immune response. Antibodies binding to gp120 V3 genotype consensus peptides were more frequently observed for FT, mainly against peptides corresponding to sequences of genotypes prevalent in the Rio de Janeiro city area, B and F. HIV-1 neutralization of HIV-1 IIIB and of four primary isolates from Rio de Janeiro was less frequently observed for plasma from the NF than the FT group, but this difference was more expressive when plasma from individuals with detectable viremia were compared to that of individuals with undetectable viral loads in the year before sample collection. Although statistically significant differences were observed only in some specific comparisons, the study indicates that presence of detectable viremia may contribute to the maintenance of a specific anti-HIV-1 humoral immune response. PMID:18060317

  9. Neutralization Properties of Simian Immunodeficiency Viruses Infecting Chimpanzees and Gorillas

    PubMed Central

    Barbian, Hannah J.; Decker, Julie M.; Bibollet-Ruche, Frederic; Galimidi, Rachel P.; West, Anthony P.; Learn, Gerald H.; Parrish, Nicholas F.; Iyer, Shilpa S.; Li, Yingying; Pace, Craig S.; Song, Ruijiang; Huang, Yaoxing; Denny, Thomas N.; Mouquet, Hugo; Martin, Loic; Acharya, Priyamvada; Zhang, Baoshan; Kwong, Peter D.; Mascola, John R.; Verrips, C. Theo; Strokappe, Nika M.; Rutten, Lucy; McCoy, Laura E.; Weiss, Robin A.; Brown, Corrine S.; Jackson, Raven; Silvestri, Guido; Connors, Mark; Burton, Dennis R.; Shaw, George M.; Nussenzweig, Michel C.; Bjorkman, Pamela J.; Ho, David D.; Farzan, Michael

    2015-01-01

    ABSTRACT Broadly cross-reactive neutralizing antibodies (bNabs) represent powerful tools to combat human immunodeficiency virus type 1 (HIV-1) infection. Here, we examined whether HIV-1-specific bNabs are capable of cross-neutralizing distantly related simian immunodeficiency viruses (SIVs) infecting central (Pan troglodytes troglodytes) (SIVcpzPtt) and eastern (Pan troglodytes schweinfurthii) (SIVcpzPts) chimpanzees (n = 11) as well as western gorillas (Gorilla gorilla gorilla) (SIVgor) (n = 1). We found that bNabs directed against the CD4 binding site (n = 10), peptidoglycans at the base of variable loop 3 (V3) (n = 5), and epitopes at the interface of surface (gp120) and membrane-bound (gp41) envelope glycoproteins (n = 5) failed to neutralize SIVcpz and SIVgor strains. In addition, apex V2-directed bNabs (n = 3) as well as llama-derived (heavy chain only) antibodies (n = 6) recognizing both the CD4 binding site and gp41 epitopes were either completely inactive or neutralized only a fraction of SIVcpzPtt strains. In contrast, one antibody targeting the membrane-proximal external region (MPER) of gp41 (10E8), functional CD4 and CCR5 receptor mimetics (eCD4-Ig, eCD4-Igmim2, CD4-218.3-E51, and CD4-218.3-E51-mim2), as well as mono- and bispecific anti-human CD4 (iMab and LM52) and CCR5 (PRO140, PRO140-10E8) receptor antibodies neutralized >90% of SIVcpz and SIVgor strains with low-nanomolar (0.13 to 8.4 nM) potency. Importantly, the latter antibodies blocked virus entry not only in TZM-bl cells but also in Cf2Th cells expressing chimpanzee CD4 and CCR5 and neutralized SIVcpz in chimpanzee CD4+ T cells, with 50% inhibitory concentrations (IC50s) ranging from 3.6 to 40.5 nM. These findings provide new insight into the protective capacity of anti-HIV-1 bNabs and identify candidates for further development to combat SIVcpz infection. PMID:25900654

  10. Analysis of human APOBEC3H haplotypes and anti-human immunodeficiency virus type 1 activity.

    PubMed

    Wang, Xiaojun; Abudu, Aierken; Son, Sungmo; Dang, Ying; Venta, Patrick J; Zheng, Yong-Hui

    2011-04-01

    Human APOBEC3H (A3H) has one cytidine deaminase domain (CDD) and inhibits the replication of retrotransposons and human immunodeficiency virus type 1 (HIV-1) in a Vif-resistant manner. Human A3H has five single amino acid polymorphisms (N15?, R18L, G105R, K121D, and E178D), and four haplotypes (I to IV) have previously been identified in various human populations. Haplotype II was primarily found in African-derived populations, and it was the only one that could be stably expressed. Here, we identified three new haplotypes from six human population samples, which we have named V, VI, and VII. Haplotypes V and VII are stably expressed and inhibit HIV-1 replication. Notably, haplotype V was identified in samples from all African-, Asian-, and Caucasian-derived populations studied. Using haplotype VII, we investigated the A3H anti-HIV-1 mechanism. We found that A3H virion packaging is independent of its CDD but dependent on a (112)YYXW(115) motif. This motif binds HIV-1 nucleocapsid in an RNA-dependent manner, and a single Y112A mutation completely disrupts A3H virion incorporation. We further studied the mechanism of A3H resistance to Vif. Although the previously identified APOBEC3G Vif-responsive motif (128)DPDY(131) is not conserved in A3H, placement of this motif into A3H does not make it become less resistant to HIV-1 Vif. We conclude that stably expressed A3H haplotypes may be more broadly distributed in humans than previously realized, and A3H protein is resistant to Vif. These results have important implications for the role of A3H in retrotransposon and HIV-1 inhibition. PMID:21270145

  11. 1592U89, a novel carbocyclic nucleoside analog with potent, selective anti-human immunodeficiency virus activity.

    PubMed Central

    Daluge, S M; Good, S S; Faletto, M B; Miller, W H; St Clair, M H; Boone, L R; Tisdale, M; Parry, N R; Reardon, J E; Dornsife, R E; Averett, D R; Krenitsky, T A

    1997-01-01

    1592U89, (-)-(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclo pentene-1-methanol, is a carbocyclic nucleoside with a unique biological profile giving potent, selective anti-human immunodeficiency virus (HIV) activity. 1592U89 was selected after evaluation of a wide variety of analogs containing a cyclopentene substitution for the 2'-deoxyriboside of natural deoxynucleosides, optimizing in vitro anti-HIV potency, oral bioavailability, and central nervous system (CNS) penetration. 1592U89 was equivalent in potency to 3'-azido-3'-deoxythymidine (AZT) in human peripheral blood lymphocyte (PBL) cultures against clinical isolates of HIV type 1 (HIV-1) from antiretroviral drug-naive patients (average 50% inhibitory concentration [IC50], 0.26 microM for 1592U89 and 0.23 microM for AZT). 1592U89 showed minimal cross-resistance (approximately twofold) with AZT and other approved HIV reverse transcriptase (RT) inhibitors. 1592U89 was synergistic in combination with AZT, the nonnucleoside RT inhibitor nevirapine, and the protease inhibitor 141W94 in MT4 cells against HIV-1 (IIIB). 1592U89 was anabolized intracellularly to its 5'-monophosphate in CD4+ CEM cells and in PBLs, but the di- and triphosphates of 1592U89 were not detected. The only triphosphate found in cells incubated with 1592U89 was that of the guanine analog (-)-carbovir (CBV). However, the in vivo pharmacokinetic, distribution, and toxicological profiles of 1592U89 were distinct from and improved over those of CBV, probably because CBV itself was not appreciably formed from 1592U89 in cells or animals (<2%). The 5'-triphosphate of CBV was a potent, selective inhibitor of HIV-1 RT, with Ki values for DNA polymerases (alpha, beta, gamma, and epsilon which were 90-, 2,900-, 1,200-, and 1,900-fold greater, respectively, than for RT (Ki, 21 nM). 1592U89 was relatively nontoxic to human bone marrow progenitors erythroid burst-forming unit and granulocyte-macrophage CFU (IC50s, 110 microM) and human leukemic and liver tumor cell lines. 1592U89 had excellent oral bioavailability (105% in the rat) and penetrated the CNS (rat brain and monkey cerebrospinal fluid) as well as AZT. Having demonstrated an excellent preclinical profile, 1592U89 has progressed to clinical evaluation in HIV-infected patients. PMID:9145874

  12. Characterization of Human Class-Switched Polymeric (Immunoglobulin M [IgM] and IgA) Anti-Human Immunodeficiency Virus Type 1 Antibodies 2F5 and 2G12

    PubMed Central

    Wolbank, Susanne; Kunert, Renate; Stiegler, Gabriela; Katinger, Hermann

    2003-01-01

    We have previously generated human monoclonal anti-human immunodeficiency virus type 1 (anti-HIV-1) antibodies 2F5IgG and 2G12IgG with an exceptional cross-clade neutralizing potential. 2F5IgG and 2G12IgG passively administrated to macaques were able to confer complete protection from both intravenous and mucosal challenge with pathogenic HIV-simian immunodeficiency virus chimeric strains and have shown beneficial effects in a phase-1 clinical trial. We now class-switched 2F5 and 2G12 to the immunoglobulin M (IgM) or IgA isotype, to enforce features like avidity, complement activation, or the potential to neutralize mucosal transmission. For this purpose we expressed functional polymeric 2F5 and 2G12 antibodies in CHO cells and evaluated their anti-HIV-1 activity in vitro. The class switch had a strong impact on the protective potential of 2F5 and 2G12. 2G12IgM inhibited HIV-1 infection of peripheral blood mononuclear cell cultures up to 28-fold-more efficiently than the corresponding IgG and neutralized all of the primary isolates tested. The 2F5 and 2G12 antibodies of all isotypes were able to interact with active human serum to inhibit viral infection. Furthermore, we demonstrated that polymeric 2F5 and 2G12 antibodies but not the corresponding IgGs could interfere with HIV-1 entry across a mucosal epithelial layer in vitro. Although polymeric 2F5 antibodies had only limited potential in the standard neutralization assay, the results from the mucosal assay suggest that 2F5 and 2G12 antibodies may have a high potential to prevent natural HIV-1 transmission in vivo. PMID:12634368

  13. Patterns of in VitroAnti-Human Immunodeficiency Virus Type 1 Antibody Production in Long-Term Nonprogressors

    Microsoft Academic Search

    Stefano Rusconi; Alberto Berlusconi; Laura Papagno; Maria Chiara Colombo; Chiara de Maddalena; Agostino Riva; Patrizia Bagnarelli; Claudia Balotta; Massimo Galli

    1997-01-01

    With the aim of evaluating the specific pattern ofin vitroantibody production (IVAP) in human immunodeficiency virus type 1 (HIV-1)-infected long-term nonprogressors (LTNPs), we tested 20 subjects who had remained asymptomatic for more than 8 years with a CD4+cell count higher than 500\\/?l and 59 patients at different stages of HIV-1 infection as controls. In cell cultures, IVAP was detected in

  14. In vitro anti-human immunodeficiency virus (HIV) activities of transition state mimetic HIV protease inhibitors containing allophenylnorstatine.

    PubMed Central

    Kageyama, S; Mimoto, T; Murakawa, Y; Nomizu, M; Ford, H; Shirasaka, T; Gulnik, S; Erickson, J; Takada, K; Hayashi, H

    1993-01-01

    Transition state mimetic tripeptide human immunodeficiency virus (HIV) protease inhibitors containing allophenylnorstatine [(2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid] were synthesized and tested for activity against HIV in vitro. Two compounds, KNI-227 and KNI-272, which were highly potent against HIV protease with little inhibition of other aspartic proteases, showed the most potent activity against the infectivity and cytopathic effect of a wide spectrum of HIV strains. As tested in target CD4+ ATH8 cells, the 50% inhibitory concentrations of KNI-227 against HIV type 1 LAI (HIV-1LAI), HIV-1RF, HIV-1MN, and HIV-2ROD were 0.1, 0.02, 0.03, and 0.1 microM, respectively, while those of KNI-272 were 0.1, 0.02, 0.04, and 0.1 microM, respectively. Both agents completely blocked the replication of 3'-azido-2',3'-dideoxythymidine-sensitive and -insensitive clinical HIV-1 isolates at 0.08 microM as tested in target phytohemagglutinin-activated peripheral blood mononuclear cells. The ratios of 50% cytotoxic concentrations to 50% inhibitory concentrations for KNI-227 and KNI-272 were approximately 2,500 and > 4,000, respectively, as assessed in peripheral blood mononuclear cells. Both compounds blocked the posttranslational cleavage of the p55 precursor protein to generate the mature p24 Gag protein in stably HIV-1-infected cells. The n-octanol-water partition coefficients of KNI-227 and KNI-272 were high, with log Po/w values of 3.79 and 3.56, respectively. Degradation of KNI-227 and KNI-272 in the presence of pepsin (1 mg/ml, pH 2.2) at 37 degrees C for 24 h was negligible. Current data warrant further careful investigations toward possible clinical application of these two novel compounds. Images PMID:8494379

  15. Anti-Human Immunodeficiency Virus Type 1 Activity, Intracellular Metabolism, and Pharmacokinetic Evaluation of 2?-Deoxy-3?-Oxa-4?-Thiocytidine

    PubMed Central

    de Muys, Jean-Marc; Gourdeau, Henriette; Nguyen-Ba, Nghe; Taylor, Debra L.; Ahmed, Parvin S.; Mansour, Tarek; Locas, Celine; Richard, Nathalie; Wainberg, Mark A.; Rando, Robert F.

    1999-01-01

    The racemic nucleoside analogue 2?-deoxy-3?-oxa-4?-thiocytidine (dOTC) is in clinical development for the treatment of human immunodeficiency virus (HIV) type 1 (HIV-1) infection. dOTC is structurally related to lamivudine (3TC), but the oxygen and sulfur in the furanosyl ring are transposed. Intracellular metabolism studies showed that dOTC is phosphorylated within cells via the deoxycytidine kinase pathway and that approximately 2 to 5% of dOTC is converted into the racemic triphosphate derivatives, which had measurable half-lives (2 to 3 hours) within cells. Both 5?-triphosphate (TP) derivatives of dOTC were more potent than 3TC-TP at inhibiting HIV-1 reverse transcriptase (RT) in vitro. The Ki values for dOTC-TP obtained against human DNA polymerases ?, ?, and ? were 5,000-, 78-, and 571-fold greater, respectively, than those for HIV RT (28 nM), indicating a good selectivity for the viral enzyme. In culture experiments, dOTC is a potent inhibitor of primary isolates of HIV-1, which were obtained from antiretroviral drug-naive patients as well as from nucleoside therapy-experienced (3TC- and/or zidovudine [AZT]-treated) patients. The mean 50% inhibitory concentration of dOTC for drug-naive isolates was 1.76 ?M, rising to only 2.53 and 2.5 ?M for viruses resistant to 3TC and viruses resistant to 3TC and AZT, respectively. This minimal change in activity is in contrast to the more dramatic changes observed when 3TC or AZT was evaluated against these same viral isolates. In tissue culture studies, the 50% toxicity levels for dOTC, which were determined by using [3H]thymidine uptake as a measure of logarithmic-phase cell proliferation, was greater than 100 ?M for all cell lines tested. In addition, after 14 days of continuous culture, at concentrations up to 10 ?M, no measurable toxic effect on HepG2 cells or mitochondrial DNA replication within these cells was observed. When administered orally to rats, dOTC was well absorbed, with a bioavailability of approximately 77%, with a high proportion (approximately 16.5% of the levels in serum) found in the cerebrospinal fluid. PMID:10428900

  16. Intracellular Metabolism and Persistence of the Anti-Human Immunodeficiency Virus Activity of 2?,3?-Didehydro-3?-Deoxy-4?-Ethynylthymidine, a Novel Thymidine Analog?

    PubMed Central

    Paintsil, Elijah; Dutschman, Ginger E.; Hu, Rong; Grill, Susan P.; Lam, Wing; Baba, Masanori; Tanaka, Hiromichi; Cheng, Yung-Chi

    2007-01-01

    The therapeutic benefits of current antiretroviral therapy are limited by the evolution of drug-resistant virus and long-term toxicity. Novel antiretroviral compounds with activity against drug-resistant viruses are needed. 2?,3?-Didehydro-3?-deoxy-4?-ethynylthymidine (4?-Ed4T), a novel thymidine analog, has potent anti-human immunodeficiency virus (HIV) activity, maintains considerable activity against multidrug-resistant HIV strains, and is less inhibitory to mitochondrial DNA synthesis in cell culture than its progenitor stavudine (D4T). We investigated the intracellular metabolism and anti-HIV activity of 4?-Ed4T. The profile of 4?-Ed4T metabolites was qualitatively similar to that for zidovudine (AZT), with the monophosphate metabolite as the major metabolite, in contrast to that for D4T, with relatively poor formation of total metabolites. The first phosphorylation step for 4?-Ed4T in cells was more efficient than that for D4T but less than that for AZT. The amount of 4?-Ed4T triphosphate (4?-Ed4TTP) was higher than that of AZTTP at 24 h in culture. There was a dose-dependent accumulation of 4?-Ed4T diphosphate and 4?-Ed4TTP on up-regulation of thymidylate kinase and 3-phosphoglycerate kinase expression in Tet-On RKO cells, respectively. The anti-HIV activity of 4?-Ed4T in cells persisted even after 48 h of drug removal from culture in comparison with AZT, D4T, and nevirapine (NVP). The order of increasing persistence of anti-HIV activity of these compounds after drug removal was 4?-Ed4T > D4T > AZT > NVP. In conclusion, with the persistence of 4?-Ed4TTP and persistent anti-HIV activity in cells, we anticipate less frequent dosing and fewer patient compliance issues than for D4T. 4?-Ed4T is a promising antiviral candidate for HIV type 1 chemotherapy. PMID:17724147

  17. Cytochrome P450 3A5 Plays a Prominent Role in the Oxidative Metabolism of the Anti-Human Immunodeficiency Virus Drug Maraviroc

    PubMed Central

    Lu, Yanhui; Hendrix, Craig W.

    2012-01-01

    Maraviroc is an anti-human immunodeficiency virus drug that acts by blocking viral entry into target cells. With use of ultra-performance liquid chromatography-mass spectrometry several monooxygenated, dioxygenated, and glucuronidated metabolites of maraviroc were identified both in vitro and in vivo. Characterization of the enzymes involved in the production of these metabolites determined that cytochrome P450 3A5 was the principal enzyme responsible for the formation of an abundant metabolite of maraviroc that resulted from oxygenation of the dichlorocyclohexane ring. For the formation of this metabolite, the Vmax values for CYP3A4 and CYP3A5 were 0.04 and 0.93 pmol · min?1 · pmol P450?1, and the Km values were 11.1 and 48.9 ?M, respectively. Furthermore, human liver microsomes isolated from donors homozygous for the loss-of-function CYP3A5*3 allele exhibited a 79% decrease in formation of this metabolite compared with those homozygous for the wild-type CYP3A5*1 allele. To probe which divergent residues between CYP3A4 and CYP3A5 might play a role in the differential activities of these enzymes toward maraviroc, mutations were introduced into both enzymes and metabolism of maraviroc was measured. A CYP3A5 L57F mutant exhibited a 61% decrease in the formation of this metabolite, whereas formation by a CYP3A4 F57L mutant was increased by 337% compared with that of the wild type. Taken together, these data provide novel insights into the biotransformation of maraviroc as well as the potential role of CYP3A4 and CYP3A5 divergent residues in the enzymatic activities of these two highly homologous enzymes. PMID:22923690

  18. 5-Chloro-2',3'-dideoxy-3'-fluorouridine (935U83), a selective anti-human immunodeficiency virus agent with an improved metabolic and toxicological profile.

    PubMed Central

    Daluge, S M; Purifoy, D J; Savina, P M; St Clair, M H; Parry, N R; Dev, I K; Novak, P; Ayers, K M; Reardon, J E; Roberts, G B

    1994-01-01

    5-Chloro-2',3'-dideoxy-3'-fluorouridine (935U83) is a selective anti-human immunodeficiency virus (HIV) agent. When tested in phytohemagglutinin-stimulated normal human peripheral blood lymphocytes against fresh clinical isolates of HIV type 1 (HIV-1) obtained from patients naive to AZT (3'-azido-3'-deoxythymidine [zidovudine]), 935U83 inhibited virus growth with an average 50% inhibitory concentration (IC50) of 1.8 microM; corresponding IC50s were 0.10 microM for FLT (3'-deoxy-3'-fluorothymidine) and 0.23, 0.49, and 0.03 microM for the approved agents AZT, ddI (2',3'-dideoxyinosine), and ddC (2',3'-dideoxycytosine), respectively. Importantly, 935U83 retained activity against HIV strains that were resistant to AZT, ddI, or ddC. Of additional interest, we were unable to generate virus which was resistant to 935U83 by passaging either HXB2 (AZT-sensitive) or RTMC (AZT-resistant) strains in the presence of high concentrations of 935U83. The anabolic profile of 935U83 was similar to that of AZT, and 935U83 triphosphate was a potent inhibitor of HIV-1 reverse transcriptase. Pharmacokinetic evaluation showed good oral bioavailability (86% in mice and 60% in monkeys) and less extensive metabolism to the glucuronide relative to AZT. 935U83 showed low toxicity. In an in vitro assay for toxicity to a human erythrocyte progenitor, erythroid burst-forming unit (BFU-E), the IC50 for 935U83 (> 400 microM) was more than 1,000-fold those of FLT (0.07 microM) and AZT (0.30 microM). Mild reversible reductions in erythrocytes and associated parameters were seen in mice dosed orally with 2,000 mg of 935U83 per kg per day for 1 and 6 months. In monkeys dosed orally with up to 700 mg/kg/day for 1 and 6 months, the only possible treatment-related finding was cataracts in 1 of 12 animals given the intermediate dose of 225 mg/kg/day. At the highest doses in mice and monkeys, maximal concentrations in plasma were more than 100-fold the anti-HIV IC50s against clinical isolates. This safety profile in animals compares very favorably with that of any of the anti-HIV drugs approved to date and has led us to begin evaluation of 935U83 in patients with HIV infection. PMID:7526782

  19. Biocompatibility of solid-dosage forms of anti-human immunodeficiency virus type 1 microbicides with the human cervicovaginal mucosa modeled ex vivo.

    PubMed

    Trifonova, Radiana T; Pasicznyk, Jenna-Malia; Fichorova, Raina N

    2006-12-01

    Topical anti-human immunodeficiency virus (HIV) microbicides are being sought to reduce the spread of HIV type 1 (HIV-1) during sexual intercourse. The success of this strategy depends upon the selection of formulations compatible with the natural vaginal mucosal barrier. This study applied ex vivo-modeled human cervicovaginal epithelium to evaluate experimental solid-dosage forms of the anti-HIV-1 microbicide cellulose acetate 1,2-benzenedicarboxylate (CAP) and over-the-counter (OTC) vaginal products for their impact on inflammatory mediators regarded as potential HIV-1-enhancing risk factors. We assessed product-induced imbalances between interleukin-1alpha (IL-1alpha) and IL-1beta and the natural IL-1 receptor antagonist (IL-1RA) and changes in levels of IL-6, tumor necrosis factor alpha, IL-8, gamma interferon inducible protein 10 (IP-10), and macrophage inflammatory protein 3alpha (MIP-3alpha), known to recruit and activate monocytes, dendritic cells, and T cells to the inflamed mucosa. CAP film and gel formulation, similarly to the hydroxyethylcellulose universal vaginal placebo gel and the OTC K-Y moisturizing gel, were nontoxic and caused no significant changes in any inflammatory biomarker. In contrast, OTC vaginal cleansing and contraceptive films containing octoxynol-9 or nonoxynol-9 (N-9) demonstrated similar levels of toxicity but distinct immunoinflammatory profiles. IL-1alpha, IL-1beta, IL-8, and IP-10 were increased after treatment with both OTC vaginal cleansing and contraceptive films; however, MIP-3alpha was significantly elevated by the N-9-based film only (P < 0.01). Although both films increased extracellular IL-1RA, the cleansing film only significantly elevated the IL-1RA/IL-1 ratio (P < 0.001). The N-9-based film decreased intracellular IL-1RA (P < 0.05), which has anti-inflammatory intracrine functions. This study identifies immunoinflammatory biomarkers that can discriminate between formulations better than toxicity assays and should be clinically validated in relevance to the risk of HIV-1 acquisition. PMID:17030562

  20. A Tight-Binding Mode of Inhibition Is Essential for Anti-Human Immunodeficiency Virus Type 1 Virucidal Activity of Nonnucleoside Reverse Transcriptase Inhibitors

    Microsoft Academic Search

    Dimitrios Motakis; Michael A. Parniak

    2002-01-01

    It was previously found that certain nonnucleoside reverse transcriptase inhibitors (NNRTI) possess viru- cidal activity against human immunodeficiency virus type 1 (HIV-1), and it was suggested that the tight- binding mode of inhibition of reverse transcriptase might be important for this virucidal activity (Borkow et al., J. Virol. 71:3023-3030, 1997). To test this, we compared six different NNRTI, including three

  1. Safety and pharmacokinetics of hyperimmune anti-human immunodeficiency virus (HIV) immunoglobulin administered to HIV-infected pregnant women and their newborns. Pediatric AIDS Clinical Trials Group Protocol 185 Pharmacokinetic Study Group.

    PubMed

    Lambert, J S; Mofenson, L M; Fletcher, C V; Moye, J; Stiehm, E R; Meyer, W A; Nemo, G J; Mathieson, B J; Hirsch, G; Sapan, C V; Cummins, L M; Jimenez, E; O'Neill, E; Kovacs, A; Stek, A

    1997-02-01

    The pharmacokinetics and safety of hyperimmune anti-human immunodeficiency virus (HIV) intravenous immunoglobulin (HIVIG) were evaluated in the first 28 maternal-infant pairs enrolled in a randomized, intravenous immunoglobulin (IVIG)-controlled trial of HIVIG maternal-infant HIV transmission prophylaxis. Using 200 mg/kg, mean half-life and volume of distribution (Vd) in women were 15 days and 72 mL/kg, respectively, after one and 32 days and 154 mL/kg after three monthly infusions, with stable 4 mL/kg/day clearance. Transplacental passage occurred. Newborn single-dose half-life, Vd, and clearance were 30 days, 143 mL/kg, and 4 mL/kg/day, respectively. HIVIG rapidly cleared maternal serum immune complex-dissociated p24 antigen, and plasma HIV-1 RNA levels were stable. Mild to moderate adverse clinical effects occurred in 2 of 103 maternal and 2 of 25 infant infusions. No adverse hematologic, blood chemistry, or immunologic effects were seen. HIVIG is well-tolerated in HIV-infected pregnant women and their newborns, clears antigenemia, crosses the placenta, and exhibits pharmacokinetics similar to those of other immunoglobulin preparations. PMID:9203648

  2. Anti-human immunodeficiency virus activity of YK-FH312 (a betulinic acid derivative), a novel compound blocking viral maturation.

    PubMed

    Kanamoto, T; Kashiwada, Y; Kanbara, K; Gotoh, K; Yoshimori, M; Goto, T; Sano, K; Nakashima, H

    2001-04-01

    Betulinic acid, a triterpenoid isolated from the methyl alcohol extract of the leaves of Syzigium claviflorum, was found to have a potent inhibitory activity against human immunodeficiency virus type 1 (HIV-1). Betulinic acid derivatives were synthesized to enhance the anti-HIV activity. Among the derivatives, 3-O-(3',3'-dimethylsuccinyl) betulinic acid, designated YK-FH312, showed the highest activity against HIV-induced cytopathic effects in HIV-1-infected MT-4 cells. To determine the step(s) of HIV replication affected by YK-FH312, a syncytium formation inhibition assay in MOLT-4/HIV-1(IIIB) and MOLT-4 coculture, a multinuclear-activation-of-galactosidase-indicator (MAGI) assay in MAGI-CCR5 cells, electron microscopic observation, and a time-of-addition assay were performed. In the syncytium formation inhibition assay or in the MAGI assay for de novo infection, the compound did not show inhibitory effects against HIV replication. Conversely, no virions were detected in HIV-1-infected cell cultures treated with YK-FH312 either by electron microscopic observation or by viral yield in the supernatant. In accordance with a p24 enzyme-linked immunosorbent assay of culture supernatant in the time-of-addition assay, YK-FH312 inhibited virus expression in the supernatant when it was added 18 h postinfection. However, Western blot analysis of the cells in the time-of-addition assay revealed that the production of viral proteins in the cells was not inhibited completely by YK-FH312. These results suggest that YK-FH312 might affect the step(s) of virion assembly and/or budding of virions, and this is a novel mechanism of action of an anti-HIV compound. PMID:11257038

  3. Potent Synergistic Anti-Human Immunodeficiency Virus (HIV) Effects Using Combinations of the CCR5 Inhibitor Aplaviroc with Other Anti-HIV Drugs?

    PubMed Central

    Nakata, Hirotomo; Steinberg, Seth M.; Koh, Yasuhiro; Maeda, Kenji; Takaoka, Yoshikazu; Tamamura, Hirokazu; Fujii, Nobutaka; Mitsuya, Hiroaki

    2008-01-01

    Aplaviroc (AVC), an experimental CCR5 inhibitor, potently blocks in vitro the infection of R5-tropic human immunodeficiency virus type 1 (R5-HIV-1) at subnanomolar 50% inhibitory concentrations. Although maraviroc is presently clinically available, further studies are required to determine the role of CCR5 inhibitors in combinations with other drugs. Here we determined anti-HIV-1 activity using combinations of AVC with various anti-HIV-1 agents, including four U.S. Food and Drug Administration-approved drugs, two CCR5 inhibitors (TAK779 and SCH-C) and two CXCR4 inhibitors (AMD3100 and TE14011). Combination effects were defined as synergistic or antagonistic when the activity of drug A combined with B was statistically greater or less, respectively, than the additive effects of drugs A and A combined and drugs B and B combined by using the Combo method, described in this paper, which provides (i) a flexible choice of interaction models and (ii) the use of nonparametric statistical methods. Synergistic effects against R5-HIV-1Ba-L and a 50:50 mixture of R5-HIV-1Ba-L and X4-HIV-1ERS104pre (HIV-1Ba-L/104pre) were seen when AVC was combined with zidovudine, nevirapine, indinavir, or enfuvirtide. Mild synergism and additivity were observed when AVC was combined with TAK779 and SCH-C, respectively. We also observed more potent synergism against HIV-1Ba-L/104pre when AVC was combined with AMD3100 or TE14011. The data demonstrate a tendency toward greater synergism with AVC plus either of the two CXCR4 inhibitors compared to the synergism obtained with combinations of AVC and other drugs, suggesting that the development of effective CXCR4 inhibitors may be important for increasing the efficacies of CCR5 inhibitors. PMID:18378711

  4. Cytokines as Adjuvants for the Induction of Anti-Human Immunodeficiency Virus Peptide Immunoglobulin G (IgG) and IgA Antibodies in Serum and Mucosal Secretions after Nasal Immunization

    PubMed Central

    Bradney, Curtis P.; Sempowski, Gregory D.; Liao, Hua-Xin; Haynes, Barton F.; Staats, Herman F.

    2002-01-01

    Safe and potent new adjuvants are needed for vaccines that are administered to mucosal surfaces. This study was performed to determine if interleukin-1? (IL-1?) combined with other proinflammatory cytokines provided mucosal adjuvant activity for induction of systemic and mucosal anti-human immunodeficiency virus (HIV) peptide antibody when intranasally administered with an HIV peptide immunogen. Nasal immunization of BALB/c mice with 10 ?g of an HIV env peptide immunogen with IL-1?, IL-12, and IL-18 on days 0, 7, 14, and 28 induced peak serum anti-HIV peptide immunoglobulin G1 (IgG1) and IgA titers of 1:131,072 and 1:7,131, respectively (P = 0.05 versus no adjuvant). The use of cholera toxin (CT) as a mucosal adjuvant induced serum IgG1 and IgA titers of 1:32,768 and 1:776, respectively. The adjuvant combination of IL-1?, IL-12, and IL-18 induced anti-HIV peptide IgA titers of 1:1,176, 1:7,131, and 1:4,705 in saliva, fecal extracts and vaginal lavage, respectively. Titers induced by the use of CT as an adjuvant were 1:223, 1:1,176, and 1:675, respectively. These results indicate that the proinflammatory cytokines IL-1?, IL-12, and IL-18 can replace CT as a mucosal adjuvant for antibody induction and are important candidates for use as mucosal adjuvants with HIV and other vaccines. PMID:11752142

  5. Emergence of gp120 V3 variants confers neutralization resistance in an R5 simian-human immunodeficiency virus-infected macaque elite neutralizer that targets the N332 glycan of the human immunodeficiency virus type 1 envelope glycoprotein.

    PubMed

    Sadjadpour, Reza; Donau, Olivia K; Shingai, Masashi; Buckler-White, Alicia; Kao, Sandra; Strebel, Klaus; Nishimura, Yoshiaki; Martin, Malcolm A

    2013-08-01

    Neutralization-resistant simian-human immunodeficiency virus AD8 (SHIVAD8) variants that emerged in an infected macaque elite neutralizer targeting the human immunodeficiency virus type 1 (HIV-1) gp120 N332 glycan acquired substitutions of critical amino acids in the V3 region rather than losing the N332 glycosylation site. One of these resistant variants, carrying the full complement of gp120 V3 changes, was also resistant to the potent anti-HIV-1 monoclonal neutralizing antibodies PGT121 and 10-1074, both of which are also dependent on the presence of the gp120 N332 glycan. PMID:23720719

  6. Emergence of gp120 V3 Variants Confers Neutralization Resistance in an R5 Simian-Human Immunodeficiency Virus-Infected Macaque Elite Neutralizer That Targets the N332 Glycan of the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein

    PubMed Central

    Sadjadpour, Reza; Donau, Olivia K.; Shingai, Masashi; Buckler-White, Alicia; Kao, Sandra; Strebel, Klaus; Nishimura, Yoshiaki

    2013-01-01

    Neutralization-resistant simian-human immunodeficiency virus AD8 (SHIVAD8) variants that emerged in an infected macaque elite neutralizer targeting the human immunodeficiency virus type 1 (HIV-1) gp120 N332 glycan acquired substitutions of critical amino acids in the V3 region rather than losing the N332 glycosylation site. One of these resistant variants, carrying the full complement of gp120 V3 changes, was also resistant to the potent anti-HIV-1 monoclonal neutralizing antibodies PGT121 and 10-1074, both of which are also dependent on the presence of the gp120 N332 glycan. PMID:23720719

  7. Preventive and therapeutic applications of neutralizing antibodies to Human Immunodeficiency Virus Type 1 (HIV-1)

    PubMed Central

    Ringe, Rajesh

    2013-01-01

    The development of a preventive vaccine to neutralize the highly variable and antigenically diverse human immunodeficiency virus type 1 (HIV-1) has been an indomitable goal. The recent discovery of a number of cross-neutralizing and potent monoclonal antibodies from elite neutralizers has provided important insights in this field. Neutralizing antibodies (NAbs) are useful in identifying neutralizing epitopes of vaccine utility and for understanding the mechanism of potent and broad cross-neutralization thus providing a modality of preventive and therapeutic value. In this article we review the current understanding on the potential use of broadly neutralizing antibodies (bNAbs) in their full-length IgG structure, engineered domain antibody or bispecific versions towards preventive and therapeutic applications. The potential implications of NAbs are discussed in the light of the recent developments as key components in vaccination against HIV-1. The development of a vaccine immunogen which elicits bNAbs and confers protective immunity remains a real challenge. PMID:24757516

  8. Modeling Virus- and Antibody-Specific Factors to Predict Human Immunodeficiency Virus (HIV-1) Neutralization Efficiency

    PubMed Central

    Haim, Hillel; Salas, Ignacio; McGee, Kathleen; Eichelberger, Noah; Winter, Elizabeth; Pacheco, Beatriz; Sodroski, Joseph

    2013-01-01

    SUMMARY Efforts to prevent human immunodeficiency virus (HIV-1) infection would benefit from understanding the factors that govern virus neutralization by antibodies. We present a mechanistic model for HIV-1 neutralization that includes both virus and antibody parameters. Variations in epitope integrity on the viral envelope glycoprotein (Env) trimer and Env reactivity to bound antibody influence neutralization susceptibility. In addition, we define an antibody-specific parameter, the perturbation factor (PF), that describes the degree of conformational change in the Env trimer required for a given antibody to bind. Minimally perturbing (low-PF) antibodies can efficiently neutralize viruses with a broad range of Env reactivities due to fast on-rates and high affinity for Env. Highly perturbing (high-PF) antibodies inhibit only viruses with reactive (perturbation-sensitive) Envs, often through irreversible mechanisms. Accounting for these quantifiable viral and antibody-associated parameters helps to predict the observed profiles of HIV-1 neutralization by antibodies with a wide range of potencies. PMID:24237700

  9. Neutralizing antibody-independent containment of immunodeficiency virus challenges by DNA priming and recombinant pox virus booster immunizations

    Microsoft Academic Search

    David C. Montefiori; R. Paul Johnson; Kelledy H. Manson; Marcia L. Kalish; Jeffrey D. Lifson; Tahir A. Rizvi; Shan Lu; Shiu-Lok Hu; Gail P. Mazzara; Dennis L. Panicali; James G. Herndon; Rhona Glickman; Maria A. Candido; Shari L. Lydy; Michael S. Wyand; Harold M. McClure; Harriet L. Robinson

    1999-01-01

    Eight different protocols were compared for their ability to raise protection against immunodeficiency virus challenges in rhesus macaques. The most promising containment of challenge infections was achieved by intradermal DNA priming followed by recombinant fowl pox virus booster immunizations. This containment did not require neutralizing antibody and was active for a series of challenges ending with a highly virulent virus

  10. Neutralizing monoclonal antibodies against human immunodeficiency virus type 2 gp120.

    PubMed

    Matsushita, S; Matsumi, S; Yoshimura, K; Morikita, T; Murakami, T; Takatsuki, K

    1995-06-01

    Monoclonal antibodies (MAbs) were obtained by immunizing mice with synthetic peptides corresponding to the third variable (V3) or the third conserved (C3) domain of the external envelope protein (gp120) of human immunodeficiency virus type 2 (HIV-2ROD). One MAb, designated B2C, which was raised against V3 peptide NKI26, bound to the surface of HIV-2-infected cells but not to their uninfected counterparts. B2C was capable of neutralizing cell-free and cell-associated virus infection in an isolate-specific fashion. The antibody-binding epitope was mapped to a 6-amino-acid peptide in the V3 variable domain which had the core sequence His-Tyr-Gln. Two MAbs, 2H1B and 2F19C, which were raised against the C3 peptide TND27 reacted with gp120 of HIV-2ROD in a Western immunoblot assay. The C3 epitopes recognized by these two MAbs appeared inaccessible because of their poor reactivity in a surface immunofluorescence assay. Although partial inhibition of syncytium formation was observed in the presence of the anti-C3 MAbs, their neutralizing activity appeared weak. Finally, the effects of these MAbs against CD4-gp120 binding were assessed. Partial inhibition of CD4-gp120 binding was observed in the presence of high concentrations of B2C. On the other hand, no inhibition of CD4-gp120 binding was observed in the presence of anti-C3 MAbs. Since complete neutralization could be achieved at a concentration corresponding to that of partial binding inhibition by B2C, some different mechanisms may be involved in the B2C-mediated neutralization. These results, taken together, indicated that analogous to the function of the V3 region of HIV-1, the V3 region of HIV-2ROD contained at least a type-specific fusion-inhibiting neutralizing epitope. In this respect, the V3 sequence of HIV-2 may be a useful target in an animal model for HIV vaccine development. PMID:7538171

  11. Neutralizing monoclonal antibodies against human immunodeficiency virus type 2 gp120.

    PubMed Central

    Matsushita, S; Matsumi, S; Yoshimura, K; Morikita, T; Murakami, T; Takatsuki, K

    1995-01-01

    Monoclonal antibodies (MAbs) were obtained by immunizing mice with synthetic peptides corresponding to the third variable (V3) or the third conserved (C3) domain of the external envelope protein (gp120) of human immunodeficiency virus type 2 (HIV-2ROD). One MAb, designated B2C, which was raised against V3 peptide NKI26, bound to the surface of HIV-2-infected cells but not to their uninfected counterparts. B2C was capable of neutralizing cell-free and cell-associated virus infection in an isolate-specific fashion. The antibody-binding epitope was mapped to a 6-amino-acid peptide in the V3 variable domain which had the core sequence His-Tyr-Gln. Two MAbs, 2H1B and 2F19C, which were raised against the C3 peptide TND27 reacted with gp120 of HIV-2ROD in a Western immunoblot assay. The C3 epitopes recognized by these two MAbs appeared inaccessible because of their poor reactivity in a surface immunofluorescence assay. Although partial inhibition of syncytium formation was observed in the presence of the anti-C3 MAbs, their neutralizing activity appeared weak. Finally, the effects of these MAbs against CD4-gp120 binding were assessed. Partial inhibition of CD4-gp120 binding was observed in the presence of high concentrations of B2C. On the other hand, no inhibition of CD4-gp120 binding was observed in the presence of anti-C3 MAbs. Since complete neutralization could be achieved at a concentration corresponding to that of partial binding inhibition by B2C, some different mechanisms may be involved in the B2C-mediated neutralization. These results, taken together, indicated that analogous to the function of the V3 region of HIV-1, the V3 region of HIV-2ROD contained at least a type-specific fusion-inhibiting neutralizing epitope. In this respect, the V3 sequence of HIV-2 may be a useful target in an animal model for HIV vaccine development. PMID:7538171

  12. Access of Antibody Molecules to the Conserved Coreceptor Binding Site on Glycoprotein gp120 Is Sterically Restricted on Primary Human Immunodeficiency Virus Type 1

    Microsoft Academic Search

    Aran F. Labrijn; Pascal Poignard; Aarti Raja; Michael B. Zwick; Karla Delgado; Michael Franti; James Binley; Veronique Vivona; Christoph Grundner; Chih-Chin Huang; Miro Venturi; Christos J. Petropoulos; Terri Wrin; Dimiter S. Dimitrov; James Robinson; Peter D. Kwong; Richard T. Wyatt; Joseph Sodroski; Dennis R. Burton

    2003-01-01

    Anti-human immunodeficiency virus type 1 (HIV-1) antibodies whose binding to gp120 is enhanced by CD4 binding (CD4i antibodies) are generally considered nonneutralizing for primary HIV-1 isolates. However, a novel CD4i-specific Fab fragment, X5, has recently been found to neutralize a wide range of primary isolates. To investigate the precise nature of the extraordinary neutralizing ability of Fab X5, we evaluated

  13. Characterization of Neutralization Epitopes of Simian Immunodeficiency Virus (SIV) Recognized by Rhesus Monoclonal Antibodies Derived from Monkeys Infected with an Attenuated SIV Strain

    Microsoft Academic Search

    Kelly Stefano Cole; Martha Alvarez; Debra H. Elliott; Hoa Lam; Effie Martin; Thao Chau; Katie Micken; Jennifer L. Rowles; Janice E. Clements; Michael Murphey-Corb; Ronald C. Montelaro; James E. Robinson

    2001-01-01

    A major limitation in the simian immunodeficiency virus (SIV) system has been the lack of reagents with which to identify the antigenic determinants that are responsible for eliciting neutralizing antibody responses in macaques infected with attenuated SIV. Most of our information on SIV neutralization determinants has come from studies with murine monoclonal antibodies (MAbs) produced in response to purified or

  14. Profiling the Specificity of Neutralizing Antibodies in a Large Panel of Plasmas from Patients Chronically Infected with Human Immunodeficiency Virus Type 1 Subtypes B and C

    Microsoft Academic Search

    James M. Binley; Elizabeth A. Lybarger; Emma T. Crooks; Michael S. Seaman; Elin Gray; Katie L. Davis; Julie M. Decker; Diane Wycuff; Linda Harris; Natalie Hawkins; Blake Wood; Cory Nathe; Douglas Richman; Georgia D. Tomaras; Frederic Bibollet-Ruche; James E. Robinson; Lynn Morris; George M. Shaw; David C. Montefiori; John R. Mascola

    2008-01-01

    Identifying the viral epitopes targeted by broad neutralizing antibodies (NAbs) that sometimes develop in human immunodeficiency virus type 1 (HIV-1)-infected subjects should assist in the design of vaccines to elicit similar responses. Here, we investigated the activities of a panel of 24 broadly neutralizing plasmas from subtype B- and C-infected donors using a series of complementary mapping methods, focusing mostly

  15. Broad, Intense Anti-Human Immunodeficiency Virus (HIV) Ex Vivo CD8 1 Responses in HIV Type 1Infected Patients: Comparison with Anti-Epstein-Barr Virus Responses and Changes during Antiretroviral Therapy

    Microsoft Academic Search

    MARC DALOD; MARION DUPUIS; JEAN-CHRISTOPHE DESCHEMIN; DIDIER SICARD; DOMINIQUE SALMON; JEAN-FRANCOIS DELFRAISSY; ALAIN VENET; MARTINE SINET; JEAN-GERARD GUILLET

    1999-01-01

    The ex vivo antiviral CD8 1 repertoires of 34 human immunodeficiency virus (HIV)-seropositive patients with various CD4 1 T-cell counts and virus loads were analyzed by gamma interferon enzyme-linked immunospot assay, using peptides derived from HIV type 1 and Epstein-Barr virus (EBV). Most patients recognized many HIV peptides, with markedly high frequencies, in association with all the HLA class I

  16. Enhanced Binding of Antibodies to Neutralization Epitopes following Thermal and Chemical Inactivation of Human Immunodeficiency Virus Type 1

    PubMed Central

    Grovit-Ferbas, K.; Hsu, J. F.; Ferbas, J.; Gudeman, V.; Chen, I. S. Y.

    2000-01-01

    Inactivation of viral particles is the basis for several vaccines currently in use. Initial attempts to use simian immunodeficiency virus to model a killed human immunodeficiency virus type 1 (HIV-1) vaccine were unsuccessful, and limited subsequent effort has been directed toward a systematic study of the requirements for a protective killed HIV-1 vaccine. Recent insights into HIV-1 virion and glycoprotein structure and neutralization epitopes led us to revisit whether inactivated HIV-1 particles could serve as the basis for an HIV-1 vaccine. Our results indicate that relatively simple processes involving thermal and chemical inactivation can inactivate HIV-1 by at least 7 logs. For some HIV-1 strains, significant amounts of envelope glycoproteins are retained in high-molecular-weight fractions. Importantly, we demonstrate retention of each of three conformation-dependent neutralization epitopes. Moreover, reactivity of monoclonal antibodies directed toward these epitopes is increased following treatment, suggesting greater exposure of the epitopes. In contrast, treatment of free envelope under the same conditions leads only to decreased antibody recognition. These inactivated virions can also be presented by human dendritic cells to direct a cell-mediated immune response in vitro. These data indicate that a systematic study of HIV-1 inactivation, gp120 retention, and epitope reactivity with conformation-specific neutralizing antibodies can provide important insights for the development of an effective killed HIV-1 vaccine. PMID:10846059

  17. Demonstration of antifungal and anti-human immunodeficiency virus reverse transcriptase activities of 6-methoxy-2-benzoxazolinone and antibacterial activity of the pineal indole 5-methoxyindole-3-acetic acid.

    PubMed

    Wang, H X; Ng, T B

    2002-06-01

    6-methoxy-2-benzoxazolinone (6-MBOA), a naturally occurring progonadal compound present in grasses with structural resemblance to melatonin, was tested for antifungal activity against Fusarium oxysporum, Rhizoctonia solani and Coprinus comatus. A variety of pineal products was also examined for the sake of comparison, including 5-methoxytryptamine, melatonin, 5-methoxytryptophol, 5-hydroxytryptamine, 5-methoxyindole-3-acetic acid and 5-hydroxytryptophol. The assay for antifungal activity was carried out in Petri plates containing potato dextrose agar. It was found that 6-MBOA most potently inhibited the growth of C. comatus, R. solani and F. oxysporum. When 6-MBOA and pineal indoles were tested for antibacterial activity against the bacterium Agrobacterium tumefaciens, 5-methoxyindole-3-acetic acid was found to be the most potent. 6-MBOA most potently inhibited human immunodeficiency virus-1 reverse transcriptase. PMID:12106902

  18. Cross-Clade Neutralization of Primary Isolates of Human Immunodeficiency Virus Type 1 by Human Monoclonal Antibodies and Tetrameric CD4IgG

    Microsoft Academic Search

    ALEXANDRA TRKOLA; AUDREY B. POMALES; HANNAH YUAN; BETTE KORBER; PAUL J. MADDON; GRAHAM P. ALLAWAY; HERMANN KATINGER; CARLOS F. BARBAS III; DENNIS R. BURTON; DAVID D. HO; ANDJOHN P. MOORE

    1995-01-01

    We have tested three human monoclonal antibodies (MAbs) IgG1b12, 2G12, and 2F5) to the envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1), and a tetrameric CD4-IgG molecule (CD4- IgG2), for the ability to neutralize primary HIV-1 isolates from the genetic clades A through F and from group O. Each of the reagents broadly and potently neutralized B-clade isolates. The

  19. A conformational switch in human immunodeficiency virus gp41 revealed by the structures of overlapping epitopes recognized by neutralizing antibodies.

    PubMed

    Pejchal, Robert; Gach, Johannes S; Brunel, Florence M; Cardoso, Rosa M; Stanfield, Robyn L; Dawson, Philip E; Burton, Dennis R; Zwick, Michael B; Wilson, Ian A

    2009-09-01

    The membrane-proximal external region (MPER) of the human immunodeficiency virus (HIV) envelope glycoprotein (gp41) is critical for viral fusion and infectivity and is the target of three of the five known broadly neutralizing HIV type 1 (HIV-1) antibodies, 2F5, Z13, and 4E10. Here, we report the crystal structure of the Fab fragment of Z13e1, an affinity-enhanced variant of monoclonal antibody Z13, in complex with a 12-residue peptide corresponding to the core epitope (W(670)NWFDITN(677)) at 1.8-A resolution. The bound peptide adopts an S-shaped conformation composed of two tandem, perpendicular helical turns. This conformation differs strikingly from the alpha-helical structure adopted by an overlapping MPER peptide bound to 4E10. Z13e1 binds to an elbow in the MPER at the membrane interface, making relatively few interactions with conserved aromatics (Trp672 and Phe673) that are critical for 4E10 recognition. The comparison of the Z13e1 and 4E10 epitope structures reveals a conformational switch such that neutralization can occur by the recognition of the different conformations and faces of the largely amphipathic MPER. The Z13e1 structure provides significant new insights into the dynamic nature of the MPER, which likely is critical for membrane fusion, and it has significant implications for mechanisms of HIV-1 neutralization by MPER antibodies and for the design of HIV-1 immunogens. PMID:19515770

  20. Human Monoclonal Antibodies Specific for Conformation-Sensitive Epitopes of V3 Neutralize Human Immunodeficiency Virus Type 1 Primary Isolates from Various Clades

    Microsoft Academic Search

    Miroslaw K. Gorny; Constance Williams; Barbara Volsky; Kathy Revesz; Sandra Cohen; Victoria R. Polonis; William J. Honnen; Samuel C. Kayman; Chavdar Krachmarov; Abraham Pinter; Susan Zolla-Pazner

    2002-01-01

    The epitopes of the V3 domain of the human immunodeficiency virus type 1 (HIV-1) gp120 glycoprotein have complex structures consisting of linear and conformational antigenic determinants. Anti-V3 antibodies (Abs) recognize both types of elements, but Abs which preferentially react to the conformational aspect of the epitopes may have more potent neutralizing activity against HIV-1, as recently suggested. To test this

  1. Evidence for Non-V3Specific Neutralizing Antibodies that Interfere with gp120\\/CD4 Binding in Human Immunodeficiency Virus 1Infected Humans

    Microsoft Academic Search

    Chang-Yuil Kang; Peter Nara; Soulaima Chamat; Vince Caralli; Tom Ryskamp; Nancy Haigwood; Roland Newman; Heinz Kohler

    1991-01-01

    Total anti-gp120 antibodies (total anti-gp120 Abs) were purified from a pool of four human immunodeficiency virus-positive (HIV^+) sera by affinity chromatography on a gp120SF2-Sepharose column and exhibited both type- and group-specific neutralizing activities. To dissect the epitope specificity of the group-specific neutralizing antibodies, CD4 attachment site-specific antibodies (CD4-site Abs) were isolated from total anti-gp120 Abs by using a CD4-blocked gp120SF2-Sepharose

  2. Human Immunodeficiency Virus Type 1 Neutralization Epitope with Conserved Architecture Elicits Early Type-Specific Antibodies in Experimentally Infected Chimpanzees

    Microsoft Academic Search

    Jaap Goudsmit; Christine Debouck; Rob H. Meloen; Lia Smit; Margreet Bakker; David M. Asher; Axel V. Wolff; Clarence J. Gibbs; D. Carleton Gajdusek

    1988-01-01

    Chimpanzees are susceptible to infection by divergent strains of human immunodeficiency virus type 1 (HIV-1), none of which cause clinical or immunological abnormalities. Chimpanzees were inoculated with one of four strains of HIV-1: human T-lymphotropic virus (HTLV) type IIIB, lymphadenopathy virus (LAV) type 1, HTLV type IIIRF, or an isolate from the brain of a patient with acquired immunodeficiency syndrome.

  3. Neutralizing Antibodies from the Sera of Human Immunodeficiency Virus Type 1-Infected Individuals Bind to Monomeric gp120 and Oligomeric gp140

    PubMed Central

    Stamatos, Nicholas M.; Mascola, John R.; Kalyanaraman, Vaniambadi S.; Louder, Mark K.; Frampton, Lynn M.; Birx, Deborah L.; VanCott, Thomas C.

    1998-01-01

    Antibodies that neutralize primary isolates of human immunodeficiency virus type 1 (HIV-1) appear during HIV-1 infection but are difficult to elicit by immunization with current vaccine products comprised of monomeric forms of HIV-1 envelope glycoprotein gp120. The limited neutralizing antibody response generated by gp120 vaccine products could be due to the absence or inaccessibility of the relevant epitopes. To determine whether neutralizing antibodies from HIV-1-infected patients bind to epitopes accessible on monomeric gp120 and/or oligomeric gp140 (ogp140), purified total immunoglobulin from the sera of two HIV-1-infected patients as well as pooled HIV immune globulin were selectively depleted of antibodies which bound to immobilized gp120 or ogp140. After passage of each immunoglobulin preparation through the respective columns, antibody titers against gp120 and ogp140 were specifically reduced at least 128-fold. The gp120- and gp140-depleted antibody fraction from each serum displayed reduced neutralization activity against three primary and two T-cell line-adapted (TCLA) HIV-1 isolates. Significant residual neutralizing activity, however, persisted in the depleted sera, indicating additional neutralizing antibody specificities. gp120- and ogp140-specific antibodies eluted from each column neutralized both primary and TCLA viruses. These data demonstrate the presence and accessibility of epitopes on both monomeric gp120 and ogp140 that are specific for antibodies that are capable of neutralizing primary isolates of HIV-1. Thus, the difficulties associated with eliciting neutralizing antibodies by using current monomeric gp120 subunit vaccines may be related less to improper protein structure and more to ineffective immunogen formulation and/or presentation. PMID:9811699

  4. CD40L-adjuvanted DNA/modified vaccinia virus Ankara simian immunodeficiency virus (SIV) vaccine enhances protection against neutralization-resistant mucosal SIV infection.

    PubMed

    Kwa, Suefen; Sadagopal, Shanmugalakshmi; Shen, Xiaoying; Hong, Jung Joo; Gangadhara, Sailaja; Basu, Rahul; Victor, Blandine; Iyer, Smita S; LaBranche, Celia C; Montefiori, David C; Tomaras, Georgia D; Villinger, Francois; Moss, Bernard; Kozlowski, Pamela A; Amara, Rama Rao

    2015-04-01

    Here, we show that a CD40L-adjuvanted DNA/modified vaccinia virus Ankara (MVA) simian immunodeficiency virus (SIV) vaccine enhances protection against a pathogenic neutralization-resistant mucosal SIV infection, improves long-term viral control, and prevents AIDS. Analyses of serum IgG antibodies to linear peptides of SIV Env revealed a strong response to V2, with targeting of fewer epitopes in the immunodominant region of gp41 (gp41-ID) and the V1 region as a correlate for enhanced protection. Greater expansion of antiviral CD8 T cells in the gut correlated with long-term viral control. PMID:25653428

  5. Neutralizing Polyclonal IgG Present during Acute Infection Prevents Rapid Disease Onset in Simian-Human Immunodeficiency Virus SHIVSF162P3-Infected Infant Rhesus Macaques

    PubMed Central

    Jaworski, J. Pablo; Kobie, James; Brower, Zachary; Malherbe, Delphine C.; Landucci, Gary; Sutton, William F.; Guo, Biwei; Reed, Jason S.; Leon, Enrique J.; Engelmann, Flora; Zheng, Bo; Legasse, Al; Park, Byung; Dickerson, Mary; Lewis, Anne D.; Colgin, Lois M. A.; Axthelm, Michael; Messaoudi, Ilhem; Sacha, Jonah B.; Burton, Dennis R.; Forthal, Donald N.; Hessell, Ann J.

    2013-01-01

    Simian-human immunodeficiency virus (SHIV) models for human immunodeficiency virus (HIV) infection have been widely used in passive studies with HIV neutralizing antibodies (NAbs) to test for protection against infection. However, because SHIV-infected adult macaques often rapidly control plasma viremia and any resulting pathogenesis is minor, the model has been unsuitable for studying the impact of antibodies on pathogenesis in infected animals. We found that SHIVSF162P3 infection in 1-month-old rhesus macaques not only results in high persistent plasma viremia but also leads to very rapid disease progression within 12 to 16 weeks. In this model, passive transfer of high doses of neutralizing IgG (SHIVIG) prevents infection. Here, we show that at lower doses, SHIVIG reduces both plasma and peripheral blood mononuclear cell (PBMC)-associated viremia and mitigates pathogenesis in infected animals. Moreover, production of endogenous NAbs correlated with lower set-point viremia and 100% survival of infected animals. New SHIV models are needed to investigate whether passively transferred antibodies or antibodies elicited by vaccination that fall short of providing sterilizing immunity impact disease progression or influence immune responses. The 1-month-old rhesus macaque SHIV model of infection provides a new tool to investigate the effects of antibodies on viral replication and clearance, mechanisms of B cell maintenance, and the induction of adaptive immunity in disease progression. PMID:23885083

  6. 21 CFR 660.50 - Anti-Human Globulin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...2010-04-01 2010-04-01 false Anti-Human Globulin. 660.50 Section 660.50...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ...SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

  7. Emergence of Autologous Neutralization?Resistant Variants from Preexisting Human Immunodeficiency Virus (HIV) Quasi Species during Virus Rebound in HIV Type 1–Infected Patients Undergoing Highly Active Antiretroviral Therapy

    Microsoft Academic Search

    Tetsuya Kimura; Kumiko Nishihara; Kazuhisa Yoshimura; Atsushi Koito; Shuzo Matsushita

    2002-01-01

    The role of neutralizing antibodies (NAbs) during virus rebound in human immunodeficiency virus type 1 (HIV-1)-i nfected patients undergoing highly active antiretroviral therapy is poorly understood. Three patients in this study had NAbs to preexisting autologous HIV-1 and an epi- sode of virus rebound after a prolonged period of virus suppression. To investigate the influence of NAbs on virus evolution,

  8. Formaldehyde-Treated, Heat-Inactivated Virions with Increased Human Immunodeficiency Virus Type 1 Env Can Be Used To Induce High-Titer Neutralizing Antibody Responses

    PubMed Central

    Poon, B.; Hsu, J. F.; Gudeman, V.; Chen, I. S. Y.; Grovit-Ferbas, K.

    2005-01-01

    The lack of success of subunit human immunodeficiency virus (HIV) type 1 vaccines to date suggests that multiple components or a complex virion structure may be required. We hypothesized that the failure of current vaccine strategies to induce protective antibodies is linked to the inability of native envelope structures to readily elicit these types of antibodies. We have previously reported on the ability of a formaldehyde-treated, heat-inactivated vaccine to induce modest antibody responses in animal vaccine models. We investigated here whether immunization for HIV with an envelope-modified, formaldehyde-stabilized, heat-inactivated virion vaccine could produce higher-titer and/or broader neutralizing antibody responses. Thus, a clade B vaccine which contains a single point mutation in gp41 (Y706C) that results in increased incorporation of oligomeric Env into virions was constructed. This vaccine was capable of inducing high-titer antibodies that could neutralize heterologous viruses, including those of clades A and C. These results further support the development of HIV vaccines with modifications in native Env structures for the induction of neutralizing antibody responses. PMID:16051814

  9. Human Immunodeficiency Virus Type 1 Escape from Cyclotriazadisulfonamide-Induced CD4-Targeted Entry Inhibition Is Associated with Increased Neutralizing Antibody Susceptibility?

    PubMed Central

    Vermeire, Kurt; Van Laethem, Kristel; Janssens, Wouter; Bell, Thomas W.; Schols, Dominique

    2009-01-01

    Continuous specific downmodulation of CD4 receptor expression in T lymphocytes by the small molecule cyclotriazadisulfonamide (CADA) selected for the CADA-resistant human immunodeficiency virus type 1 (HIV-1) NL4.3 virus containing unique mutations in the C4 and V5 regions of gp120, likely stabilizing the CD4-binding conformation. The amino acid changes in Env were associated with decreased susceptibility to anti-CD4 monoclonal antibody treatment of the cells and with higher susceptibility of the virus to soluble CD4. In addition, the acquired ability of a CADA-resistant virus to infect cells with low CD4 expression was associated with an increased susceptibility of the virus to neutralizing antibodies from sera of several HIV-1-infected patients. PMID:19570853

  10. Identification of amino acid substitutions associated with neutralization phenotype in the human immunodeficiency virus type-1 subtype C gp120

    PubMed Central

    Kirchherr, Jennifer L; Hamilton, Jennifer; Lu, Xiaozhi; Gnanakaran, S; Muldoon, Mark; Daniels, Marcus; Kasongo, Webster; Chalwe, Victor; Mulenga, Chanda; Mwananyanda, Lawrence; Musonda, Rosemary M; Yuan, Xing; Montefiori, David C; Korber, Bette T; Haynes, Barton F; Gao, Feng

    2010-01-01

    Neutralizing antibodies (Nabs) are thought to play an important role in prevention and control of HIV-1 infection and should be targeted by an AIDS vaccine. It is critical to understand how HIV-1 induces Nabs by analyzing viral sequences in both tested viruses and sera. Neutralization susceptibility to antibodies in autologous and heterologous plasma was determined for multiple Envs (3–6) from each of 15 subtype C infected-individuals. Heterologous neutralization was divided into two distinct groups: plasma with strong, cross-reactive neutralization (N=9) and plasma with weak neutralization (N=6). Plasma with cross-reactive heterologous Nabs also more potently neutralized contemporaneous autologous viruses. Analysis of Env sequences in plasma from both groups revealed a three-amino acid substitution pattern in the V4 region that was associated with greater neutralization potency and breadth. Identification of such potential neutralization signatures may have important implications for the development of HIV-1 vaccines capable of inducing Nabs to subtype C HIV-1. PMID:21036380

  11. Neutralizing antibody responses in macaques induced by human immunodeficiency virus type 1 monovalent or trivalent envelope glycoproteins.

    PubMed

    Quinnan, Gerald V; Zhang, Pengfei; Dong, Ming; Chen, Hong; Feng, Yan-Ru; Lewis, Mark; Broder, Christopher C

    2013-01-01

    A major goal of efforts to develop a vaccine to prevent HIV-1 infection is induction of broadly cross-reactive neutralizing antibodies (bcnAb). In previous studies we have demonstrated induction of neutralizing antibodies that did cross-react among multiple primary and laboratory strains of HIV-1, but neutralized with limited potency. In the present study we tested the hypothesis that immunization with multiple HIV-1 envelope glycoproteins (Envs) would result in a more potent and cross-reactive neutralizing response. One Env, CM243(N610Q), was selected on the basis of studies of the effects of single and multiple mutations of the four gp41 glycosylation sites. The other two Envs included R2 (subtype B) and 14/00/4 (subtype F), both of which were obtained from donors with bcnAb. Rhesus monkeys were immunized using a prime boost regimen as in previous studies. Individual groups of monkeys were immunized with either one of the three Envs or all three. The single N610Q and N615Q mutations of CM243 Env did not disrupt protein secretion, processing into, or reactivity with mAbs, unlike other single or multiple deglycosylation mutations. In rabbit studies the N610Q mutation alone or in combination was associated with an enhanced neutralizing response against homologous and heterologous subtype E viruses. In the subsequent monkey study the response induced by the R2 Env regimen was equivalent to the trivalent regimen and superior to the other monovalent regimens against the virus panel used for testing. The 14/00/4 Env induced responses superior to CM243(N610Q). The results indicate that elimination of the glycosylation site near the gp41 loop results in enhanced immunogenicity, but that immunization of monkeys with these three distinct Envs was not more immunogenic than with one. PMID:23533650

  12. Neutralizing Antibody Responses in Macaques Induced by Human Immunodeficiency Virus Type 1 Monovalent or Trivalent Envelope Glycoproteins

    PubMed Central

    Quinnan, Gerald V.; Zhang, Pengfei; Dong, Ming; Chen, Hong; Feng, Yan-Ru; Lewis, Mark; Broder, Christopher C.

    2013-01-01

    A major goal of efforts to develop a vaccine to prevent HIV-1 infection is induction of broadly cross-reactive neutralizing antibodies (bcnAb). In previous studies we have demonstrated induction of neutralizing antibodies that did cross-react among multiple primary and laboratory strains of HIV-1, but neutralized with limited potency. In the present study we tested the hypothesis that immunization with multiple HIV-1 envelope glycoproteins (Envs) would result in a more potent and cross-reactive neutralizing response. One Env, CM243(N610Q), was selected on the basis of studies of the effects of single and multiple mutations of the four gp41 glycosylation sites. The other two Envs included R2 (subtype B) and 14/00/4 (subtype F), both of which were obtained from donors with bcnAb. Rhesus monkeys were immunized using a prime boost regimen as in previous studies. Individual groups of monkeys were immunized with either one of the three Envs or all three. The single N610Q and N615Q mutations of CM243 Env did not disrupt protein secretion, processing into, or reactivity with mAbs, unlike other single or multiple deglycosylation mutations. In rabbit studies the N610Q mutation alone or in combination was associated with an enhanced neutralizing response against homologous and heterologous subtype E viruses. In the subsequent monkey study the response induced by the R2 Env regimen was equivalent to the trivalent regimen and superior to the other monovalent regimens against the virus panel used for testing. The 14/00/4 Env induced responses superior to CM243(N610Q). The results indicate that elimination of the glycosylation site near the gp41 loop results in enhanced immunogenicity, but that immunization of monkeys with these three distinct Envs was not more immunogenic than with one. PMID:23533650

  13. Human immunodeficiency virus 1. Predominance of a group-specific neutralizing epitope that persists despite genetic variation

    PubMed Central

    1989-01-01

    HIV-1 is known to show a high degree of genetic diversity, which may have major implications for disease pathogenesis and prevention. If every divergent isolate represented a distinct serotype, then effective vaccination might be impossible. However, using a sensitive new plaque- forming assay for HIV-1, we have found that most infected patients make neutralizing antibodies, predominantly to a group-specific epitope shared among three highly divergent isolates. This epitope persists among divergent isolates and rarely mutates, despite the rapid overall mutation rate of HIV-1, suggesting that it may participate in an essential viral function. These findings, plus the rarity of reinfections among these patients, suggest that HIV-1 may be more susceptible to a vaccine strategy based on a group-specific neutralizing epitope than was previously suspected. PMID:2478654

  14. Polymerase chain reaction evidence for human immunodeficiency virus 1 neutralization by passive immunization in patients with AIDS and AIDS-related complex.

    PubMed Central

    Karpas, A; Hewlett, I K; Hill, F; Gray, J; Byron, N; Gilgen, D; Bally, V; Oates, J K; Gazzard, B; Epstein, J E

    1990-01-01

    We tried to assess the long-term safety and potential efficacy of passive immunization in AIDS-related-complex (ARC) and AIDS patients. We also wanted to establish whether hyperimmune plasma from healthy human immunodeficiency virus 1 (HIV-1)-infected individuals clears the cell-free virus from circulation. Using the polymerase chain reaction (PCR), we were able to provide conclusive evidence that hyperimmune plasma is effective and maintains long-term neutralization of viremia. Using the cell test, we found that in most patients the total antibody level was maintained; in one of the ARC patients, it actually increased 8-fold and has remained at that level for nearly 2 years. The CD4+ cell count decreased in the AIDS patients but was stable in the ARC patient. Clinically, there was an initial improvement in all patients, but five of six of the advanced/terminal AIDS patients had died by month 17. Our studies suggest that passive immunization may be safe in ARC and AIDS patients. It reduces HIV-1 viremia to levels undetectable even by PCR. To advanced/terminal patients, the benefit is of limited duration, while to ARC patients it may be long-term. Therefore, passive immunization should start early in the disease. Images PMID:2145579

  15. Immunodeficiency disorders

    MedlinePLUS

    ... that affect T cells may cause repeated Candida (yeast) infections. Inherited combined immunodeficiency affects both T cells ... infections (including some forms of pneumonia or repeated yeast infections) Tests used to help diagnose an immunodeficiency ...

  16. The C108g Epitope in the V2 Domain of gp120 Functions as a Potent Neutralization Target When Introduced into Envelope Proteins Derived from Human Immunodeficiency Virus Type 1 Primary Isolates

    PubMed Central

    Pinter, Abraham; Honnen, William J.; D'Agostino, Paul; Gorny, Miroslaw K.; Zolla-Pazner, Susan; Kayman, Samuel C.

    2005-01-01

    Monoclonal antibodies (MAbs) directed against epitopes in the V2 domain of human immunodeficiency virus type 1 gp120 often possess neutralizing activity, but these generally are highly type specific, neutralize only laboratory isolates, or have low potency. The most potent of these is C108g, directed against a type-specific epitope in HXB2 and BaL gp120s, which is glycan dependent and, in contrast to previous reports, dependent on intact disulfide bonds. This epitope was introduced into two primary Envs, derived from a neutralization-sensitive (SF162) and a neutralization-resistant (JR-FL) isolate, by substitution of two residues and, for SF162, addition of an N-linked glycosylation site. C108g effectively neutralized both variant Envs with considerably higher potency than standard MAbs against the V3 and CD4-binding domains and the broadly neutralizing MAbs 2G12 and 2F5. These amino acid substitutions also introduced the epitope recognized by a second V2-specific MAb, 10/76b, but this MAb possessed potent neutralizing activity only in the absence of the glycan required for C108g reactivity. In contrast to other gp120-specific neutralizing MAbs, C108g did not block binding of soluble Env proteins to either the CD4 or the CCR5 receptor, but studies with a fusion-arrested Env indicated that C108g neutralized at a step preceding the one blocked by the gp41-specific MAb, 2F5. These results indicate that the V1/V2 domain possesses targets that mediate potent neutralization of primary viral isolates via a novel mechanism and suggest that inclusion of carbohydrate determinants into these epitopes may help overcome the indirect masking effects that limit the neutralizing potency of antibodies commonly produced after infection. PMID:15890930

  17. Potent and synergistic neutralization of human immunodeficiency virus (HIV) type 1 primary isolates by hyperimmune anti-HIV immunoglobulin combined with monoclonal antibodies 2F5 and 2G12.

    PubMed Central

    Mascola, J R; Louder, M K; VanCott, T C; Sapan, C V; Lambert, J S; Muenz, L R; Bunow, B; Birx, D L; Robb, M L

    1997-01-01

    Three antibody reagents that neutralize primary human immunodeficiency virus type 1 (HIV-1) isolates were tested for magnitude and breadth of neutralization when used alone or in double or triple combinations. Hyperimmune anti-HIV immunoglobulin (HIVIG) is derived from the plasma of HIV-1-infected donors, and monoclonal antibodies (MAbs) 2F5 and 2G12 bind to distinct regions of the HIV-1 envelope glycoprotein. The antibodies were initially tested against a panel of 15 clade B HIV-1 isolates, using a single concentration that is achievable in vivo (HIVIG, 2,500 microg/ml; MAbs, 25 microg/ml). Individual antibody reagents neutralized many of the viruses tested, but antibody potency varied substantially among the viruses. The virus neutralization produced by double combinations of HIVIG plus 2F5 or 2G12, the two MAbs together, or the triple combination of HIVIG, 2F5, and 2G12 was generally equal to or greater than that predicted by the effect of individual antibodies. Overall, the triple combination displayed the greatest magnitude and breadth of neutralization. Synergistic neutralization was evaluated by analyzing data from dose-response curves of each individual antibody reagent compared to the triple combination and was demonstrated against each of four viruses tested. Therefore, combinations of polyclonal and monoclonal anti-HIV antibodies can produce additive or synergistic neutralization of primary HIV-1 isolates. Passive immunotherapy for treatment or prophylaxis of HIV-1 should consider mixtures of potent neutralizing antibody reagents to expand the magnitude and breadth of virus neutralization. PMID:9311792

  18. Crystal structures of human immunodeficiency virus type 1 (HIV-1) neutralizing antibody 2219 in complex with three different V3 peptides reveal a new binding mode for HIV-1 cross-reactivity.

    PubMed

    Stanfield, Robyn L; Gorny, Miroslaw K; Zolla-Pazner, Susan; Wilson, Ian A

    2006-06-01

    Human monoclonal antibody 2219 is a neutralizing antibody isolated from a human immunodeficiency virus type 1-infected individual. 2219 was originally selected for binding to a V3 fusion protein and can neutralize primary isolates from subtypes B, A, and F. Thus, 2219 represents a cross-reactive, human anti-V3 antibody. Fab 2219 binds to one face of the variable V3 beta-hairpin, primarily contacting conserved residues on the N-terminal beta-strand of V3, leaving the V3 crown or tip largely accessible. Three V3/2219 complexes reveal the antibody-bound conformations for both the N- and C-terminal regions that flank the V3 crown and illustrate how twisting of the V3 loop alters the relative dispositions and pairing of the amino acids in the adjacent V3 beta-strands and how the antibody can accommodate V3 loops with different sequences. PMID:16731948

  19. INTRACELLULAR BOVINE CYTOKINE ANALYSIS WITH ANTI-HUMAN CYTOKINE MABS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flow cytometric analysis of intracellular cytokines has proven useful for assay of human and rodent immune cell function. Limited availability of commercial mAbs to bovine cytokines has prevented application of this method to bovine immune cells. We have used anti-human IFN-gamma and IL-8 mAbs to ...

  20. Improved Virus Neutralization by Plant-produced Anti-HIV Antibodies with a Homogeneous ?1,4-Galactosylated N-Glycan Profile*

    PubMed Central

    Strasser, Richard; Castilho, Alexandra; Stadlmann, Johannes; Kunert, Renate; Quendler, Heribert; Gattinger, Pia; Jez, Jakub; Rademacher, Thomas; Altmann, Friedrich; Mach, Lukas; Steinkellner, Herta

    2009-01-01

    It is well established that proper N-glycosylation significantly influences the efficacy of monoclonal antibodies (mAbs). However, the specific immunological relevance of individual mAb-associated N-glycan structures is currently largely unknown, because of the heterogeneous N-glycan profiles of mAbs when produced in mammalian cells. Here we report on the generation of a plant-based expression platform allowing the efficient production of mAbs with a homogeneous ?1,4-galactosylated N-glycosylation structure, the major N-glycan species present on serum IgG. This was achieved by the expression of a highly active modified version of the human ?1,4-galactosyltransferase in glycoengineered plants lacking plant-specific glycosylation. Moreover, we demonstrate that two anti-human immunodeficiency virus mAbs with fully ?1,4-galactosylated N-glycans display improved virus neutralization potency when compared with other glycoforms produced in plants and Chinese hamster ovary cells. These findings indicate that mAbs containing such homogeneous N-glycan structures should display improved in vivo activities. Our system, using expression of mAbs in tobacco plants engineered for post-translational protein processing, provides a new means of overcoming the two hurdles that limit the therapeutic use of anti-human immunodeficiency virus mAbs in global health initiatives, low biological potency and high production costs. PMID:19478090

  1. The First Hypervariable Region of the gp120 Env Glycoprotein Defines the Neutralizing Susceptibility of Heterologous Human Immunodeficiency Virus Type 1 Isolates to Neutralizing Antibodies Elicited by the SF162gp140 Immunogen

    Microsoft Academic Search

    Lance K. Ching; Giorgos Vlachogiannis; Katherine A. Bosch; Leonidas Stamatatos

    2008-01-01

    Current vaccine efforts to elicit cross-reactive neutralizing antibodies (NAbs) against human immunodefi- ciency virus (HIV) focus on the engineering of soluble mimetics of the trimeric HIV Env glycoprotein (com- monly termed gp140 immunogens). Such immunogens are thought to be more effective than previously tested monomeric gp120 immunogens at eliciting cross-reactive NAbs. Still, the breadth of neutralizing antibody responses elicited by

  2. Stable Docking of Neutralizing Human Immunodeficiency Virus Type 1 gp41 Membrane-Proximal External Region Monoclonal Antibodies 2F5 and 4E10 Is Dependent on the Membrane Immersion Depth of Their Epitope Regions ?

    PubMed Central

    Dennison, S. Moses; Stewart, Shelley M.; Stempel, Kathryn C.; Liao, Hua-Xin; Haynes, Barton F.; Alam, S. Munir

    2009-01-01

    The binding of neutralizing antibodies 2F5 and 4E10 to human immunodeficiency virus type 1 (HIV-1) gp41 involves both the viral membrane and gp41 membrane proximal external region (MPER) epitopes. In this study, we have used several biophysical tools to examine the secondary structure, orientation, and depth of immersion of gp41 MPER peptides in liposomes and to determine how the orientation of the MPER with lipids affects the binding kinetics of monoclonal antibodies (MAbs) 2F5 and 4E10. The binding of 2F5 and 4E10 both to their respective nominal epitopes and to a biepitope (includes 2F5 and 4E10 epitopes) MPER peptide-liposome conjugate was best described by a two-step encounter-docking model. Analysis of the binding kinetics and the effect of temperature on the binding stability of 2F5 and 4E10 to MPER peptide-liposome conjugates revealed that the docking of 4E10 was relatively slower and thermodynamically less favorable. The results of fluorescence-quenching and fluorescence resonance energy transfer experiments showed that the 2F5 epitope was more solvent exposed, whereas the 4E10 epitope was immersed in the polar-apolar interfacial region of the lipid bilayer. A circular dichroism spectroscopic study demonstrated that the nominal epitope and biepitope MPER peptides adopted ordered structures with differing helical contents when anchored to liposomes. Furthermore, anchoring of MPER peptides to the membrane via a hydrophobic anchor sequence was required for efficient MAb docking. These results support the model that the ability of 2F5 and 4E10 to bind to membrane lipid is required for stable docking to membrane-embedded MPER residues. These data have important implications for the design and use of peptide-liposome conjugates as immunogens for the induction of MPER-neutralizing antibodies. PMID:19640992

  3. Immunization of Rabbits with Highly Purified, Soluble, Trimeric Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Induces a Vigorous B Cell Response and Broadly Cross-Reactive Neutralization

    PubMed Central

    Quinnan, Gerald V.; Onabajo, Olusegun; Zhang, Pengfei; Yan, Lianying; Mattapallil, Joseph J.; Zhang, Zhiqiang; Dong, Ming; Lu, Min; Montefiori, David; LaBranche, Celia; Broder, Christopher C.

    2014-01-01

    Previously we described induction of cross-reactive HIV-1 neutralizing antibody responses in rabbits using a soluble HIV-1 gp140 envelope glycoprotein (Env) in an adjuvant containing monophosphoryl lipid A (MPL) and QS21 (AS02A). Here, we compared different forms of the same HIV-1 strain R2 Env for antigenic and biophysical characteristics, and in rabbits characterized the extent of B cell induction for specific antibody expression and secretion and neutralizing responses. The forms of this Env that were produced in and purified from stably transformed 293T cells included a primarily dimeric gp140, a trimeric gp140 appended to a GCN4 trimerization domain (gp140-GCN4), gp140-GCN4 with a 15 amino acid flexible linker between the gp120 and gp41 ectodomain (gp140-GCN4-L), also trimeric, and a gp140 with the flexible linker purified from cell culture supernatants as either dimer (gp140-L(D)) or monomer (gp140-L(M)). Multimeric states of the Env proteins were assessed by native gel electrophoresis and analytical ultracentrifugation. The different forms of gp140 bound broadly cross-reactive neutralizing (BCN) human monoclonal antibodies (mAbs) similarly in ELISA and immunoprecipitation assays. All Envs bound CD4i mAbs in the presence and absence of sCD4, as reported for the R2 Env. Weak neutralization of some strains of HIV-1 was seen after two additional doses in AS02A. Rabbits that were given a seventh dose of gp140-GCN4-L developed BCN responses that were weak to moderate, similar to our previous report. The specificity of these responses did not appear similar to that of any of the known BCN human mAbs. Induction of spleen B cell and plasma cells producing immunoglobulins that bound trimeric gp140-GCN4-L was vigorous, based on ELISpot and flow cytometry analyses. The results demonstrate that highly purified gp140-GCN4-L trimer in adjuvant elicits BCN responses in rabbits accompanied by vigorous B cell induction. PMID:24846288

  4. In Vitro Comparison of Topical Microbicides for Prevention of Human Immunodeficiency Virus Type 1 Transmission

    Microsoft Academic Search

    Charlene S. Dezzutti; V. Nicole James; Artur Ramos; Sharon T. Sullivan; Aladin Siddig; Timothy J. Bush; Lisa A. Grohskopf; Lynn Paxton; Shambavi Subbarao; Clyde E. Hart

    2004-01-01

    A standardized protocol was used to compare cellular toxicities and anti-human immunodeficiency virus type 1 (HIV-1) activities of candidate microbicides formulated for human use. The microbicides evaluated were cellulose acetate phthalate (CAP), Carraguard, K-Y plus nonoxynol-9 (KY-N9), PRO 2000 (0.5 and 4%), SPL7013 (5%), UC781 (0.1 and 1%), and Vena Gel, along with their accompanying placebos. Products were evaluated for

  5. Structure-Based Design of a Protein Immunogen that Displays an HIV-1 gp41 Neutralizing Epitope

    SciTech Connect

    Stanfield, Robyn L.; Julien, Jean-Philippe; Pejchal, Robert; Gach, Johannes S.; Zwick, Michael B.; Wilson, Ian A. (Scripps)

    2012-06-27

    Antibody Z13e1 is a relatively broadly neutralizing anti-human immunodeficiency virus type 1 antibody that recognizes the membrane-proximal external region (MPER) of the human immunodeficiency virus type 1 envelope glycoprotein gp41. Based on the crystal structure of an MPER epitope peptide in complex with Z13e1 Fab, we identified an unrelated protein, interleukin (IL)-22, with a surface-exposed region that is structurally homologous in its backbone to the gp41 Z13e1 epitope. By grafting the gp41 Z13e1 epitope sequence onto the structurally homologous region in IL-22, we engineered a novel protein (Z13-IL22-2) that contains the MPER epitope sequence for use as a potential immunogen and as a reagent for the detection of Z13e1-like antibodies. The Z13-IL22-2 protein binds Fab Z13e1 with a K{sub d} of 73 nM. The crystal structure of Z13-IL22-2 in complex with Fab Z13e1 shows that the epitope region is faithfully replicated in the Fab-bound scaffold protein; however, isothermal calorimetry studies indicate that Fab binding to Z13-IL22-2 is not a lock-and-key event, leaving open the question of whether conformational changes upon binding occur in the Fab, in Z13-IL-22, or in both.

  6. Structure-based design of a protein immunogen that displays an HIV-1 gp41 neutralizing epitope.

    PubMed

    Stanfield, Robyn L; Julien, Jean-Philippe; Pejchal, Robert; Gach, Johannes S; Zwick, Michael B; Wilson, Ian A

    2011-12-01

    Antibody Z13e1 is a relatively broadly neutralizing anti-human immunodeficiency virus type 1 antibody that recognizes the membrane-proximal external region (MPER) of the human immunodeficiency virus type 1 envelope glycoprotein gp41. Based on the crystal structure of an MPER epitope peptide in complex with Z13e1 Fab, we identified an unrelated protein, interleukin (IL)-22, with a surface-exposed region that is structurally homologous in its backbone to the gp41 Z13e1 epitope. By grafting the gp41 Z13e1 epitope sequence onto the structurally homologous region in IL-22, we engineered a novel protein (Z13-IL22-2) that contains the MPER epitope sequence for use as a potential immunogen and as a reagent for the detection of Z13e1-like antibodies. The Z13-IL22-2 protein binds Fab Z13e1 with a K(d) of 73 nM. The crystal structure of Z13-IL22-2 in complex with Fab Z13e1 shows that the epitope region is faithfully replicated in the Fab-bound scaffold protein; however, isothermal calorimetry studies indicate that Fab binding to Z13-IL22-2 is not a lock-and-key event, leaving open the question of whether conformational changes upon binding occur in the Fab, in Z13-IL-22, or in both. PMID:22033480

  7. Decreasing sensitivity to RANTES (regulated on activation, normally T cell-expressed and -secreted) neutralization of CC chemokine receptor 5-using, non-syncytium-inducing virus variants in the course of human immunodeficiency virus type 1 infection

    Microsoft Academic Search

    David Kwa; B. Boeser-Nunnink; Jos Dekker; Jose Vingerhoed; Harry Hiemstra; Hanneke Schuitemaker

    2003-01-01

    In approximately half of human immunodeficiency virus (HIV) type 1-infected individuals, the development of CXC chemokine receptor 4-using, syncytium-inducing (SI) virus variants precedes a rapid progression to acquired immunodeficiency syndrome (AIDS). In other individuals, only CC chemokine receptor 5-using (R5), non-SI (NSI) virus variants are present throughout infection. These individuals may be either long-term survivors (LTSs) or rapid progressors. The

  8. Development of new versions of anti-human CD34 monoclonal antibodies with potentially reduced immunogenicity

    Microsoft Academic Search

    Weizhu Qian; Ling Wang; Bohua Li; Hao Wang; Sheng Hou; Xueyu Hong; Dapeng Zhang; Yajun Guo

    2008-01-01

    Despite the widespread clinical use of CD34 antibodies for the purification of human hematopoietic stem\\/progenitor cells, all the current anti-human CD34 monoclonal antibodies (mAbs) are murine, which have the potential to elicit human antimouse antibody (HAMA) immune response. In the present study, we developed three new mouse anti-human CD34 mAbs which, respectively, belonged to class I, class II and class

  9. Simian immunodeficiency virus (SIV) envelope quasispecies transmission and evolution in infant rhesus macaques after oral challenge with uncloned SIVmac251: increased diversity is associated with neutralizing antibodies and improved survival in previously immunized animals

    Microsoft Academic Search

    Jennifer L Greenier; Koen KA Van Rompay; David Montefiori; Patricia Earl; Bernard Moss; Marta L Marthas

    2005-01-01

    BACKGROUND: Oral infection of infant macaques with simian immunodeficiency virus (SIV) is a useful animal model to test interventions to reduce postnatal HIV transmission via breast-feeding. We previously demonstrated that immunization of infant rhesus macaques with either modified vaccinia virus Ankara (MVA) expressing SIV Gag, Pol and Env, or live-attenuated SIVmac1A11 resulted in lower viremia and longer survival compared to

  10. Immunodeficiency in childhood

    Microsoft Academic Search

    Michelle Hernandez; John F. Bastian

    2006-01-01

    Primary immunodeficiency disorders (PIDs) continue to illuminate mechanisms of human immunity and hypersensitivity. New discoveries\\u000a in common variable immunodeficiency, the most enigmatic of PID syndromes, reveal molecular pathways of importance in human\\u000a antibody production. FOXP3 mutations demonstrate the essential role that T-regulatory cells play in controlling autoantibody formation and disease.\\u000a Interleukin-1 receptor-associated kinase 4 deficiency emphasizes the key role that

  11. Characterization of Neutralization Epitopes in the V2 Region of Human Immunodeficiency Virus Type 1 gp120: Role of Glycosylation in the Correct Folding of the V1\\/V2 Domain

    Microsoft Academic Search

    Z. WU; S. C. KAYMAN; W. HONNEN; K. REVESZ; H. CHEN; S. VIJH-WARRIER; S. A. TILLEY; J. MCKEATING; C. SHOTTON

    A number of monoclonal antibodies (MAbs) with various levels of neutralizing activity that recognize epitopes in the V1\\/V2 domain of LAI-related gp120s have been described. These include rodent antibodies directed against linear and conformational epitopes and a chimpanzee MAb, C108G, with extremely potent neutralizing activity directed against a glycan-dependent epitope. A fusion glycoprotein expression system that expressed the isolated V1\\/V2

  12. CD8+-Cell-Mediated Suppression of Virulent Simian Immunodeficiency Virus during Tenofovir Treatment

    PubMed Central

    Van Rompay, Koen K. A.; Singh, Raman P.; Pahar, Bapi; Sodora, Donald L.; Wingfield, Casey; Lawson, Jonathan R.; Marthas, Marta L.; Bischofberger, Norbert

    2004-01-01

    The ability of tenofovir to suppress viremia in simian immunodeficiency virus (SIV)-infected macaques for years despite the presence of virulent viral mutants with reduced in vitro susceptibility is unprecedented in this animal model. In vivo cell depletion experiments demonstrate that tenofovir's ability to suppress viremia during acute and chronic infection is significantly dependent on the presence of CD8+ lymphocytes. Continuous tenofovir treatment was required to maintain low viremia. Although it is unclear whether this immune-mediated suppression of viremia is linked to tenofovir's direct antiviral efficacy or is due to independent immunomodulatory effects, these studies prove the concept that antiviral immune responses can play a crucial role in suppressing viremia during anti-human immunodeficiency virus drug therapy. PMID:15113912

  13. Transglutaminase-catalyzed covalent multimerization of Camelidae anti-human TNF single domain antibodies improves neutralizing activity.

    PubMed

    Plagmann, Ingo; Chalaris, Athena; Kruglov, Andrei A; Nedospasov, Sergei; Rosenstiel, Philip; Rose-John, Stefan; Scheller, Jürgen

    2009-06-15

    Tumor necrosis factor (TNF) plays an important role in chronic inflammatory disorders, such as Rheumatoid Arthritis and Crohn's disease. Recently, monoclonal Camelidae variable heavy-chain domain-only antibodies (V(H)H) were developed to antagonize the action of human TNF (hTNF). Here, we show that hTNF-V(H)H does not interfere with hTNF trimerization, but competes with hTNF for hTNF-receptor binding. Moreover, we describe posttranslational dimerization and multimerization of hTNF-V(H)H molecules in vitro catalyzed by microbial transglutaminases (MTG). The ribonuclease S-tag-peptide was shown to act as a peptidyl substrate in covalent protein cross-linking reactions catalyzed by MTG from Streptomyces mobaraensis. The S-tag sequence was C-terminally fused to the hTNF-V(H)H and the fusion protein was expressed and purified from Escherichia coli culture supernatants. hTNF-V(H)H-S-tag fusion proteins were efficiently dimerized and multimerized by MTG whereas hTNF-V(H)H was not susceptible to protein cross-linking. Cell cytotoxicity assays, using hTNF as apoptosis inducing cytokine, revealed that dimerized and multimerized hTNF-V(H)H proteins were much more active than the monomeric hTNF-V(H)H. We hypothesize that improved inhibition by dimeric and multimeric single chain hTNF-V(H)H proteins is caused by avidity effects. PMID:19439388

  14. The antiviral agents, MAP30 and GAP31, are not toxic to human spermatozoa and may be useful in preventing the sexual transmission of human immunodeficiency virus type 1

    Microsoft Academic Search

    Courtney A Schreiber; Livia Wan; Yongtao Sun; Lucy Lu; Lewis C Krey; Sylvia Lee-Huang

    1999-01-01

    Objective: To investigate the effects of two virucidal compounds, MAP30 (Momordica anti–human immunodeficiency virus [HIV] protein; molecular weight, 30 kd) and GAP31 (Gelonium anti-HIV protein; molecular weight, 31 kd), obtained from Momordica charantia and Gelonium multiflorum, respectively, on the motility and vitality of human spermatocytes.Design: Prospective, controlled study.Setting: New York University School of Medicine.Patient(s): Ten healthy men undergoing evaluation for

  15. Efficient Neutralization of Primary Isolates of HIV1 by a Recombinant Human Monoclonal Antibody

    Microsoft Academic Search

    Dennis R. Burton; Jayashree Pyati; Raju Koduri; Stephen J. Sharp; George B. Thornton; Paul W. H. I. Parren; Lynette S. W. Sawyer; R. Michael Hendry; Nancy Dunlop; Peter L. Nara; Michael Lamacchia; Eileen Garratty; E. Richard Stiehm; Yvonne J. Bryson; Yunzhen Cao; John P. Moore; David D. Ho; Carlos F. Barbas III

    1994-01-01

    The ability of antibodies to neutralize diverse primary isolates of human immunodeficiency virus-type 1 in vitro has been questioned, with implications for the likely efficacy of vaccines. A recombinant human antibody to envelope glycoprotein gp120 was generated and used to show that primary isolates are not refractory to antibody neutralization. The recombinant antibody neutralized more than 75 percent of the

  16. Effects of Anti-Human Neutrophil Antibodies In Vitro. QUANTITATIVE STUDIES

    PubMed Central

    Boxer, Laurence A.; Stossel, Thomas P.

    1974-01-01

    Opsonic, antiphagocytic, cytotoxic, and metabolic effects of homologous and heterologous antibodies against human neutrophils were analyzed by means of quantitative assays to facilitate detection of antibody activity, and to probe membrane function of these cells. Normal human neutrophils were purified by gradient centrifugation, sensitized with heat-inactivated antineutrophil antisera, and incubated with rabbit alveolar macrophages in balanced salt solution containing nitroblue tetrazolium. The macrophages engulfed sensitized neutrophils and reduced nitroblue tetrazolium to formazan in phagocytic vacuoles. The initial rate of nitroblue tetrazolium reduction by macrophages ingesting the neutrophils was measured spectrophotometrically. Neutrophils treated with rabbit anti-human leukocyte antiserum or IgG, with sera from mothers of infants with neonatal isoimmune neutropenia, and with 27% of sera from frequently transfused patients promoted rapid rates of nitroblue tetrazolium reduction by alveolar macrophages. This indicates that antineutrophil antibodies without added complement opsonized neutrophils for ingestion by the macrophages. Some sera from frequently transfused patients with opsonic activity for certain donors' neutrophils did not agglutinate these neutrophils (44%), did not lyse them in the presence of fresh plasma (47%), and did not inhibit phagocytosis of particles by the neutrophils (26%). The reverse was not observed. The opsonic activity of antineutrophil antiserum appears to be the most sensitive and a quantitative means of detecting antibody activity in vitro. Low concentrations of rabbit anti-human leukocyte antisera or IgG stimulated the ingestion rate of unopsonized or opsonized particles by human neutrophils, and, as previously reported by others, enhanced rates of oxidation of [1-14C]glucose by the cells. High concentrations of the antisera or IgG inhibited ingestion. All concentrations of homologous antineutrophil antisera tested only inhibited ingestion of particles by neutrophils and none altered rates of resting glucose oxidation by the cells. The findings suggest that heterologous antibodies disturb membrane antigens that trigger oxidative metabolism and enhance as well as inhibit ingestion, and that these antigens are common to all human neutrophils. In contrast to other studies with antimacrophage antibodies, antineutrophil antibodies altered phagocytic rates of both unopsonized and opsonized particles although there were differences in dose-response curves depending on the type of particle tested. Thus, antineutrophil antibodies do not merely cover selected receptor sites. Images PMID:4208468

  17. Human immunodeficiency virus endocrinopathy

    PubMed Central

    Sinha, Uma; Sengupta, Nilanjan; Mukhopadhyay, Prasanta; Roy, Keshab Sinha

    2011-01-01

    Human immunodeficiency virus (HIV) endocrinopathy encompasses a broad spectrum of disorders. Almost all the endocrine organs are virtually affected by HIV infection. HIV can directly alter glandular function. More commonly secondary endocrine dysfunction occurs due to opportunistic infections and neoplasms in immunocompromised state. The complex interaction between HIV infection and endocrine system may be manifested as subtle biochemical and hormonal perturbation to overt glandular failure. Antiretroviral therapy as well as other essential medications often result in adverse endocrinal consequences. Apart from adrenal insufficiency, hypogonadism, diabetes and bone loss, AIDS wasting syndrome and HIV lipodystrophy need special reference. Endocrinal evaluation should proceed as in other patients with suspected endocrine dysfunction. Available treatment options have been shown to improve quality of life and long-term mortality in AIDS patients. PMID:22028995

  18. An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

    PubMed Central

    Traub, Stephanie; Nikonova, Alexandra; Carruthers, Alan; Dunmore, Rebecca; Vousden, Katherine A.; Gogsadze, Leila; Hao, Weidong; Zhu, Qing; Bernard, Katie; Zhu, Jie; Dymond, Michael; McLean, Gary R.; Walton, Ross P.; Glanville, Nicholas; Humbles, Alison; Khaitov, Musa; Wells, Ted; Kolbeck, Roland; Leishman, Andrew J.; Sleeman, Matthew A.

    2013-01-01

    Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ?90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo. PMID:23935498

  19. Testing for Human Immunodeficiency Virus

    MedlinePLUS

    ... babies. Once in the blood, HIV attacks the immune system . As the immune system weakens, the body becomes ... immune system and causes acquired immunodeficiency syndrome (AIDS). Immune System: The body’s natural defense system against foreign substances ...

  20. Protection of monkeys vaccinated with vpr- and\\/or nef-defective simian immunodeficiency virus strain mac\\/human immunodeficiency virus type 1 chimeric viruses: a potential candidate live-attenuated human AIDS vaccine

    Microsoft Academic Search

    Tatsuhiko Igarashi; Yasushi Ami; Hiroshi Yamamoto; Riri Shibata; Takeo Kuwata; Ryozaburo Mukai; Katsuaki Shinohara; Toshihiko Komatsu; Akio Adachi; Masanori Hayami

    Two simian immunodeficiency virus strain mac (SIVmac)\\/human immunodeficiency virus type 1(HIV-1) chimeric viruses (SHIVs), designated NM-3 and NM-3n, with env derived from HIV-1 and defective vpr (plus defective nef for NM-3), were inoculated into seven macaques. These macaques were transiently or persistently infected and most of them produced long-lasting neutralizing anti- bodies and Env-specific killer T cells to HIV-1 with

  1. Immunization of Chimpanzees Confers Protection Aganist Challenge with Human Immunodeficiency Virus

    Microsoft Academic Search

    Marc Girard; Marie-Paule Kieny; Abraham Pinter; Francoise Barre-Sinoussi; Peter Nara; Hanno Kolbe; Kenro Kusumi; Angnes Chaput; Todd Reinhart; Elizabeth Muchmore; Jorge Ronco; Michel Kaczorek; Elisabeth Gomard; Jean-Claude Gluckman; Patricia N. Fultz

    1991-01-01

    Sustained high titers of neutralizing antibodies were elicited in three chimpanzees after sequential injections of different human immunodeficiency virus 1 (HIV-1) antigen preparations derived from the HIV-1 BRU strain that included whole inactivated virus or purified recombinant proteins and then synthetic peptides identical to the major HIV-1 neutralizing epitope V3. The animals were challenged i.v. with 40 chimpanzee infectious doses

  2. Use of Standardized SCID-hu Thy\\/Liv Mouse Model for Preclinical Efficacy Testing of Anti-Human Immunodeficiency Virus Type 1 Compounds

    Microsoft Academic Search

    LINDA RABIN; MARA HINCENBERGS; MARY BETH MORENO; SUZETTE WARREN; VALERIE LINQUIST; ROELF DATEMA; BRIGITTE CHARPIOT; JAN SEIFERT; HIDETO KANESHIMA; ANDJOSEPH M. MCCUNE

    measure the representation of CD41and CD81cells, and cocultivation for the isolation of virus. Efficacy tests in this model are demonstrated with the nucleoside analogs zidovudine and dideoxyinosine and with the nonnucleoside reverse transcriptase inhibitor nevirapine. This small-animal model should be particularly useful in the preclinical prioritization of lead compounds within a common chemical class, in the evaluation of alternative in

  3. Anti-AIDS Agents 78 †. Design, Synthesis, Metabolic Stability Assessment, and Antiviral Evaluation of Novel Betulinic Acid Derivatives as Potent Anti-Human Immunodeficiency Virus (HIV) Agents

    PubMed Central

    Qian, Keduo; Yu, Donglei; Chen, Chin-Ho; Huang, Li; Morris-Natschke, Susan L.; Nitz, Theodore J.; Salzwedel, Karl; Reddick, Mary; Allaway, Graham P.; Lee, Kuo-Hsiung

    2009-01-01

    In a continuing study of potent anti-HIV agents, seventeen 28,30-disubstituted betulinic acid (BA, 1) derivatives, as well as seven novel 3,28-disubstituted BA analogs were designed, synthesized, and evaluated for in vitro antiviral activity. Among them, compound 21 showed an improved solubility and equal anti-HIV potency (EC50: 0.09 ?M), when compared to HIV entry inhibitors 3b (IC9564) and 4 (A43-D). Using a cyclic secondary amine to form the C-28 amide bond increased the metabolic stability of the derivatives significantly in pooled human liver microsomes. The most potent compounds 47 and 48 displayed potent anti-HIV activity with EC50 values of 0.007 ?M and 0.006 ?M, respectively. These results are slightly better than that of bevirimat (2), which is currently in Phase IIb clinical trials. Compounds 47 and 48 should serve as attractive promising leads to develop next generation, metabolically stable, 3,28-disubstituted bifunctional HIV-1 inhibitors as clinical trials candidates. PMID:19388685

  4. In Vitro Preclinical Testing of Nonoxynol-9 as Potential Anti-Human Immunodeficiency Virus Microbicide: a Retrospective Analysis of Results from Five Laboratories

    PubMed Central

    Beer, Brigitte E.; Doncel, Gustavo F.; Krebs, Fred C.; Shattock, Robin J.; Fletcher, Patricia S.; Buckheit, Robert W.; Watson, Karen; Dezzutti, Charlene S.; Cummins, James E.; Bromley, Ena; Richardson-Harman, Nicola; Pallansch, Luke A.; Lackman-Smith, Carol; Osterling, Clay; Mankowski, Marie; Miller, Shendra R.; Catalone, Bradley J.; Welsh, Patricia A.; Howett, Mary K.; Wigdahl, Brian; Turpin, Jim A.; Reichelderfer, Patricia

    2006-01-01

    The first product to be clinically evaluated as a microbicide contained the nonionic surfactant nonoxynol-9 (nonylphenoxypolyethoxyethanol; N-9). Many laboratories have used N-9 as a control compound for microbicide assays. However, no published comparisons of the results among laboratories or attempts to establish standardized protocols for preclinical testing of microbicides have been performed. In this study, we compared results from 127 N-9 toxicity and 72 efficacy assays that were generated in five different laboratories over the last six years and were performed with 14 different cell lines or tissues. Intra-assay reproducibility was measured at two-, three-, and fivefold differences using standard deviations. Interassay reproducibility was assessed using general linear models, and interaction between variables was studied using step-wise regression. The intra-assay reproducibility within the same N-9 concentration, cell type, assay duration, and laboratory was consistent at the twofold level of standard deviations. For interassay reproducibility, cell line, duration of assay, and N-9 concentration were all significant sources of variability (P < 0.01). Half-maximal toxicity concentrations for N-9 were similar between laboratories for assays of similar exposure durations, but these similarities decreased with lower test concentrations of N-9. Results for both long (>24 h) and short (<2 h) exposures of cells to N-9 showed variability, while assays with 4 to 8 h of N-9 exposure gave results that were not significantly different. This is the first analysis to compare preclinical N-9 toxicity levels that were obtained by different laboratories using various protocols. This comparative work can be used to develop standardized microbicide testing protocols that will help advance potential microbicides to clinical trials. PMID:16436731

  5. Inhibitors of CTP biosynthesis potentiate the anti-human immunodeficiency virus type 1 activity of 3TC in activated peripheral blood mononuclear cells

    Microsoft Academic Search

    Nathalie Dereuddre-Bosquet; Béatrice Roy; Kate Routledge; Pascal Clayette; Georges Foucault; Michel Lepoivre

    2004-01-01

    Unlike hydroxyurea, the CTP synthetase inhibitor acivicin and, to a lesser extent, two other inhibitors of CTP synthesis, increased the phosphorylation and anti-HIV-1 activity of 3TC in PHA-P-activated PBMC. These data suggest that to improve the antiretroviral activity of 3TC, it may be worth focusing on inhibition of CTP synthesis.

  6. Priming of Anti-Human Immunodeficiency Virus (HIV) CD8^+ Cytotoxic T Cells in vivo by Carrier-Free HIV Synthetic Peptides

    NASA Astrophysics Data System (ADS)

    Hart, Mary Kate; Weinhold, Kent J.; Scearce, Richard M.; Washburn, Eileen M.; Clark, Cynthia A.; Palker, Thomas J.; Haynes, Barton F.

    1991-11-01

    The generation of antiviral cytotoxic T lymphocytes (CTLs) is a critical component of the immune response to viral infections. A safe and nontoxic vaccine for AIDS would optimally use a carrier-free synthetic peptide immunogen containing only components of HIV necessary for induction of protective immune responses. We report that hybrid synthetic peptides containing either a HIV envelope gp120 T-cell determinant (T1) or the envelope gp41 fusion domain (F) N-terminal to HIV CTL determinants are capable of priming murine CD8^+, major histocompatibility complex class I-restricted anti-HIV CTLs in vivo. These data demonstrate that carrier-free, nonderivatized synthetic peptides can be used in vivo to induce anti-HIV CTL responses.

  7. Human immunodeficiency virus infection and pneumothorax.

    PubMed

    Terzi, Eirini; Zarogoulidis, Konstantinos; Kougioumtzi, Ioanna; Dryllis, Georgios; Kioumis, Ioannis; Pitsiou, Georgia; Machairiotis, Nikolaos; Katsikogiannis, Nikolaos; Tsiouda, Theodora; Madesis, Athanasios; Karaiskos, Theodoros; Zarogoulidis, Paul

    2014-10-01

    Pneumothorax is a serious and relatively frequent complication of human immunodeficiency virus (HIV) infection that may associate with increased morbidity and mortality and may prove difficult to manage, especially in patients with acquired immunodeficiency syndrome (AIDS). PMID:25337392

  8. Actin cytoskeletal defects in immunodeficiency

    PubMed Central

    Moulding, Dale A; Record, Julien; Malinova, Dessislava; Thrasher, Adrian J

    2013-01-01

    The importance of the cytoskeleton in mounting a successful immune response is evident from the wide range of defects that occur in actin-related primary immunodeficiencies (PIDs). Studies of these PIDs have revealed a pivotal role for the actin cytoskeleton in almost all stages of immune system function, from hematopoiesis and immune cell development, through to recruitment, migration, intercellular and intracellular signaling, and activation of both innate and adaptive immune responses. The major focus of this review is the immune defects that result from mutations in the Wiskott-Aldrich syndrome gene (WAS), which have a broad impact on many different processes and give rise to clinically heterogeneous immunodeficiencies. We also discuss other related genetic defects and the possibility of identifying new genetic causes of cytoskeletal immunodeficiency. PMID:24117828

  9. Primary immunodeficiencies of dogs and cats.

    PubMed

    DeBey, Mary C

    2010-05-01

    Primary immunodeficiencies are congenital defects that affect formation or function of the immune system. Congenital immunodeficiency should be considered as a differential diagnosis for repeated infections in a young animal. Defects in the immune system may lead to complete or partial loss of immunity. Some animals with mild immunodeficiency can be managed with long-term antibiotic therapy. PMID:20471526

  10. Primary immunodeficiencies underlying fungal infections

    PubMed Central

    Lanternier, Fanny; Cypowyj, Sophie; Picard, Capucine; Bustamante, Jacinta; Lortholary, Olivier; Casanova, Jean-Laurent; Puel, Anne

    2014-01-01

    Purpose of review We review the primary immunodeficiencies underlying an increasing variety of superficial and invasive fungal infections. We also stress that the occurrence of such fungal infections should lead physicians to search for the corresponding single-gene inborn errors of immunity. Finally, we suggest that other fungal infections may also result from hitherto unknown inborn errors of immunity, at least in some patients with no known risk factors. Recent findings An increasing number of primary immunodeficiencies are being shown to underlie fungal infectious diseases in children and young adults. Inborn errors of the phagocyte NADPH oxidase complex (chronic granulomatous disease), severe congenital neutropenia and leukocyte adhesion deficiency type I confer a predisposition to invasive aspergillosis and candidiasis. More rarely, inborn errors of IFN-? immunity underlie endemic mycoses. Inborn errors of IL-17 immunity have recently been shown to underlie chronic mucocutaneous candidiasis, whereas inborn errors of CARD9 immunity underlie deep dermatophytosis and invasive candidiasis. Summary Chronic mucocutaneous candidiasis, invasive candidiasis, invasive aspergillosis, deep dermatophytosis, pneumocystosis, and endemic mycoses can all be caused by primary immunodeficiencies. Each type of infection is highly suggestive of a specific type of primary immunodeficiency. In the absence of overt risk factors, single-gene inborn errors of immunity should be sought in children and young adults with these and other fungal diseases. PMID:24240293

  11. Cross-reactivity of anti-human, anti-porcine and anti-bovine cytokine antibodies with cetacean tissues.

    PubMed

    Jaber, J R; Pérez, J; Zafra, R; Herráez, P; Rodríguez, F; Arbelo, M; de los Monteros, A Espinosa; Fernández, A

    2010-07-01

    The cross-reactivity of monoclonal antibodies specific for human, porcine and bovine cytokines was evaluated for three cetacean species: Atlantic spotted dolphins (Stenella frontalis), striped dolphins (Stenella coeruleoalba) and fin whales (Balaenoptera physalus). Formalin-fixed and snap-frozen tissue sections of lung, spleen, liver and mesenteric lymph node were evaluated. T and B lymphocytes and monocytes/macrophages were detected by use of anti-human CD3, IgG and lysozyme polyclonal antibodies (pAbs), respectively. These reagents were successfully applied to both fixed and frozen tissues. Anti-human interleukin (IL)-1 alpha, IL-1 beta, IL-8, tumour necrosis factor (TNF)-alpha and CD25, anti-porcine IL-2, IL-6, IL-10, and anti-bovine IL-4 and interferon (IFN)-gamma antibodies produced immunolabelling in cetacean snap-frozen lymph node sections similar to that obtained with tissue from the species of origin, but they did not react with formalin-fixed tissue sections. Anti-porcine IL-12 pAb did not react with snap-frozen cetacean tissue samples. Macrophages and lymphocytes were the most common cells immunolabelled with the anti-cytokine antibodies. This panel of anti-cytokine antibodies may be used to evaluate cytokine expression in snap-frozen tissue samples from the cetacean species tested. PMID:20163803

  12. Inactivation of Human Immunodeficiency Virus Type 1 by Porphyrins

    PubMed Central

    Vzorov, Andrei N.; Dixon, Dabney W.; Trommel, Jenna S.; Marzilli, Luigi G.; Compans, Richard W.

    2002-01-01

    We have evaluated the anti-human immunodeficiency virus (HIV) activity of a series of natural and synthetic porphyrins to identify compounds that could potentially be used as microbicides to provide a defense against infection by sexually transmitted virus. For assays we used an epithelial HeLa-CD4 cell line with an integrated long terminal repeat-?-galactosidase gene. For structure-activity analysis, we divided the porphyrins tested into three classes: (i) natural porphyrins, (ii) metallo-tetraphenylporphyrin tetrasulfonate (metallo-TPPS4) derivatives, and (iii) sulfonated tetra-arylporphyrin derivatives. None of the natural porphyrins studied reduced infection by more than 80% at a concentration of 5 ?g/ml in these assays. Some metal chelates of TPPS4 were more active, and a number of sulfonated tetra-aryl derivatives showed significantly higher activity. Some of the most active compounds were the sulfonated tetranaphthyl porphyrin (TNapPS), sulfonated tetra-anthracenyl porphyrin (TAnthPS), and sulfonated 2,6-difluoro-meso-tetraphenylporphine [TPP(2,6-F2)S] and its copper chelate [TPP(2,6-F2)S,Cu], which reduced infection by 99, 96, 94, and 96%, respectively. Our observations indicate that at least some of these compounds are virucidal, i.e., that they render the virus noninfectious. The active compounds were found to inhibit binding of the HIV type 1 gp120 to CD4 and also to completely inhibit the ability of Env proteins expressed from recombinant vectors to induce cell fusion with receptor-bearing target cells. These results support the conclusion that modified porphyrins exhibit substantial activity against HIV and that their target is the HIV Env protein. PMID:12435696

  13. HIV1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites

    Microsoft Academic Search

    Peter D. Kwong; Michael L. Doyle; David J. Casper; Claudia Cicala; Stephanie A. Leavitt; Shahzad Majeed; Tavis D. Steenbeke; Miro Venturi; Irwin Chaiken; Michael Fung; Hermann Katinger; Paul W. I. H. Parren; James Robinson; Donald Van Ryk; Liping Wang; Dennis R. Burton; Ernesto Freire; Richard Wyatt; Joseph Sodroski; Wayne A. Hendrickson; James Arthos

    2002-01-01

    The ability of human immunodeficiency virus (HIV-1) to persist and cause AIDS is dependent on its avoidance of antibody-mediated neutralization. The virus elicits abundant, envelope-directed antibodies that have little neutralization capacity. This lack of neutralization is paradoxical, given the functional conservation and exposure of receptor-binding sites on the gp120 envelope glycoprotein, which are larger than the typical antibody footprint and

  14. The role of feline syncytium forming virus in feline immunodeficiency virus-mediated acquired immunodeficiency 

    E-print Network

    Zenger, Elizabeth

    1991-01-01

    THE ROLE OF FELINE SYNCYTIUM FORMING VIRUS IN FELINE IMMUNODEFICIENCY VIRUS-MEDIATED ACQUIRED IMMUNODEFICIENCY A Thesis by ELIZABETH ZENGER Submitted to the Office of Graduate Studies of Texas ARM University in partial fulfillment... of the requirements for the degree of MASTER OF SCIENCE December 1991 Major Subject: Veterinary Medicine and Surgery THE ROLE OF FELINE SYNCYTIUM FORMING VIRUS IN FELINE IMMUNODEFICIENCY VIRUS-MEDIATED ACQUIRED IMMUNODEFICIENCY A Thesis by ELIZABETH ZENGER...

  15. Genetics Home Reference: X-linked severe combined immunodeficiency

    MedlinePLUS

    ... combined immunodeficiency MedlinePlus Encyclopedia: Immunodeficiency Disorders National Marrow Donor Program: Severe Combined Immunodeficiency and Transplant You might also find information on the diagnosis or management of X-linked SCID in Educational resources and ...

  16. Non-specific binding of anti-human IgE peroxidase-linked conjugates to legume proteins in immunoblots.

    PubMed

    Herian, A M; Taylor, S L

    1991-07-01

    Non-specific binding was observed in immunoblotting of legume proteins with commercial anti-human IgE and IgG antibodies conjugated with peroxidase when incubations were conducted without prior incubation with human sera of legume-allergic individuals. The non-specific binding was encountered with ten legume species. It was not associated with endogenous peroxidase or the peanut or soybean lectins. The degree of non-specific binding diminished with roasted peanut extracts as compared to raw peanut extracts. The cause of this non-specific binding remains unknown, although it may be related to the animal source of the antiserum or the method of conjugation of the antibody with peroxidase. This interference in immunoblotting can be easily detected with controls lacking incubation with human sera. PMID:2066561

  17. THE SPECTRUM OF PRIMARY IMMUNODEFICIENCY DISORDERS IN IRAN

    Microsoft Academic Search

    A. Aghamohammadi; M. Moin; A. Farhoudi; Z. Pourpak; N. Rezaei; K. Abolmaali; M. Movahedi; M. Gharagozlou; B. Mir; Saeid Ghazi; L. Atarod; T. Hojati Ashrafi; M. Mahmoudi; A. Isaeian; D. Mansouri; S. Arshi; N. Javaher Trash; H. Akbari; R. Sherkat; A. Hashemzadeh; I. Mohammadzadeh

    Epidemiological studies have shown wide geographical and racial variation in the prevalence and patterns of immunodeficiency disorders. To determine the frequency of primary immunodeficiencies (PID) in Iran, the Iranian Primary Immunodeficiency Registry (IPIDR) was organized in 1999. The diagnosis of immunodeficiency in our patients was based on standard criteria. The patients' data were extracted, by using a uniform questionnaire from

  18. Establishment of monoclonal anti-human CD26 antibodies suitable for immunostaining of formalin-fixed tissue

    PubMed Central

    2014-01-01

    Background A T cell costimulatory molecule with dipeptidyl peptidase IV (DPPIV) activity in its extracellular region, CD26 is a multifunctional molecule associated with various proteins such as adenosine deaminase, caveolin-1, CXCR4, collagen, and fibronectin, while playing an important role in the regulation of inflammatory responses and tumor biology. We have focused on CD26 as a novel therapeutic target for various tumors and immune disorders, and have developed a humanized anti-CD26 monoclonal antibody (mAb), YS110, which is currently being evaluated in a phase I clinical trial for patients with CD26-expressing tumors, including malignant mesothelioma. Since detection of tumor CD26 expression is required for determining potential eligibility for YS110 therapy, the development of anti-human CD26 mAb that can clearly and reliably detect the denatured CD26 molecule in the formalin-fixed paraffin-embedded tissues is critical. Methods To develop novel anti-CD26 mAbs capable of binding to the denatured CD26, we immunized mice with CD26 protein denatured in urea buffer. After the fusion of splenocytes and myeloma cells, the mAbs were screened for specific reactivity with human CD26 by flow cytometry, enzyme-linked immunosorbent assay, and immunohistochemistry. The binding competitiveness of novel anti-CD26 mAbs with the humanized anti-CD26 mAb YS110 was also examined. Results We have succeeded in developing novel anti-human CD26 mAbs suitable for immunohistochemical staining of CD26 in formalin-fixed tissue sections with reliable clarity and intensity. Importantly, some of these mAbs exhibit no cross-reactivity with the humanized anti-CD26 mAb. Conclusions These novel mAbs are potentially useful as companion diagnostic agents to analyze CD26 expression in the clinical setting while advancing future CD26-related research. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5987140221097729 PMID:24502396

  19. Anti-human protein S antibody induces tissue factor expression through a direct interaction with platelet phosphofructokinase

    PubMed Central

    Chen, Changyi; Liao, Dan; Wang, Jing; Liang, Zhengdong; Yao, Qizhi

    2013-01-01

    Introduction Autoantibodies including anti-human protein S antibody (anti-hPS Ab) and anti-human protein C antibody (anti-hPC Ab) can be detected in patients with autoimmune diseases with hypercoagulability. The objective of the present study was to determine the effects and molecular pathways of these autoantibodies on tissue factor (TF) expression in human coronary artery endothelial cells (HCAECs). Materials and Methods HCAECs were treated with anti-hPS Ab or anti-hPC Ab for 3 hours. TF expression was measured by real-time PCR and Western blot. TF-mediated procoagulant activity was determined by a commercial kit. MAPK phosphorylation was analyzed by Bio-Plex luminex immunoassay and Western blot. The potential proteins interacting with anti-hPS Ab were studied by immunoprecipitation, mass spectrometry and in vitro pull-down assay. Results Anti-hPS Ab, but not anti-hPC Ab, specifically induced TF expression and TF-mediated procoagulant activity in HCAECs in a concentration-dependent manner. This effect was confirmed in human umbilical endothelial cells (HUVECs). ERK1/2 phosphorylation was induced by anti-hPS Ab treatment, while inhibition of ERK1/2 by U0216 partially blocked anti-hPS Ab-induced TF upregulation (P<0.05). In addition, anti-hPS Ab specifically cross-interacted with platelet phosphofructokinase (PFKP) in HCAECs. Anti-hPS Ab was able to directly inhibit PFKP activities in HCAECs. Furthermore, silencing of PFKP by PFKP shRNA resulted in TF upregulation in HCAECs, while activation of PFKP by fructose-6-phosphate partially blocked the effect of anti-hPS Ab on TF upregulation (P<0.05). Conclusions Anti-hPS Ab induces TF expression through a direct interaction with PFKP and ERK1/2 activation in HCAECs. Anti-hPS Ab may directly contribute to vascular thrombosis in the patient with autoimmune disorders. PMID:24331211

  20. Current Perspectives on Primary Immunodeficiency Diseases

    PubMed Central

    Kumar, Arvind; Teuber, Suzanne S.; Gershwin, M. Eric

    2006-01-01

    Since the original description of X-linked agammaglobulinemia in 1952, the number of independent primary immunodeficiency diseases (PIDs) has expanded to more than 100 entities. By definition, a PID is a genetically determined disorder resulting in enhanced susceptibility to infectious disease. Despite the heritable nature of these diseases, some PIDs are clinically manifested only after prerequisite environmental exposures but they often have associated malignant, allergic, or autoimmune manifestations. PIDs must be distinguished from secondary or acquired immunodeficiencies, which are far more common. In this review, we will place these immunodeficiencies in the context of both clinical and laboratory presentations as well as highlight the known genetic basis. PMID:17162365

  1. Use of Human Immunodeficiency Virus Nucleoside-Analog Reverse Transcriptase Inhibitors to Control Human Immunodeficiency Virus

    NSDL National Science Digital Library

    American Society For Microbiology

    2005-03-11

    This animation illustrates how human immunodeficiency virus (HIV) nucleoside-analog reverse transcriptase inhibitors (zidovudine, didanosine, zalcitabine, stavudine, lamivudine, and abacavir) inhibit replication of the HIV.

  2. Two novel inhibitory anti-human factor XI antibodies prevent cessation of blood flow in a murine venous thrombosis model.

    PubMed

    van Montfoort, M L; Knaup, V L; Marquart, J A; Bakhtiari, K; Castellino, F J; Hack, C E; Meijers, J C M

    2013-11-01

    Coagulation factor XI (FXI) is a promising target for anticoagulation, because of its major role in thrombosis and relatively minor role in haemostasis. This implies that inhibition of FXI can prevent thrombosis without causing bleeding. It was our aim to investigate the antithrombotic properties of two novel inhibitory anti-human FXI antibodies (?FXI-175 and ?FXI-203). The in vitro properties of both antibodies were analysed using standard clotting assays and calibrated automated thrombography. For the in vivo model we used FXI knockout mice, in which FXI plasma levels were restored with purified human FXI. Thrombosis was induced by applying ferric chloride to the vena cava inferior, after which time to occlusion was analysed. A tail bleeding assay was used to investigate the safety of both antibodies. Using calibrated automated thrombography, both antibodies inhibited thrombin generation initiated via the intrinsic pathway. In contrast, upon tissue factor (TF)-initiated thrombin generation, ?FXI-203 did not inhibit thrombin generation, while ?FXI-175 inhibited thrombin generation only at low concentrations of TF. In the murine thrombosis model, the vena cava inferior remained patent for 25 minutes (min) in mice treated with ?FXI-175 and for 12.5 min in ?FXI-203 treated animals, which was significantly longer than in placebo-treated animals (5 min, p<0.05). Neither antibody caused severe blood loss in a tail bleeding assay. In conclusion, the two inhibitory antibodies against FXI prevented cessation of blood flow in a murine thrombosis model without inducing a bleeding tendency. PMID:23925504

  3. Learning about Severe Combined Immunodeficiency (SCID)

    MedlinePLUS

    ... From The Journal of Allergy and Clinical Immunology Learning About Severe Combined Immunodeficiency (SCID) What is Severe ... grow normally Infections that require intravenous antibiotic treatment Deep-seated infections, such as pneumonia that affects an ...

  4. Warts and All: HPV in Primary Immunodeficiencies

    PubMed Central

    Leiding, Jennifer W.; Holland, Steven M.

    2012-01-01

    Infection with human papilloma virus (HPV) is almost universal and eventually asymptomatic, but pathologic infection with HPV is severe, recurrent, and recalcitrant to therapy. It is also an underappreciated manifestation of primary immunodeficiency. Mutations in EVER1, EVER2, GATA2, CXCR4, and DOCK8 are typically associated with extensive HPV infections, whereas several other primary immune defects have severe HPV much less frequently. We review immunodeficiencies with severe HPV infections and the mechanisms underlying them. PMID:23036745

  5. Inhibition of human immunodeficiency virus type 1 replication by SDZ NIM 811, a nonimmunosuppressive cyclosporine analog.

    PubMed Central

    Rosenwirth, B; Billich, A; Datema, R; Donatsch, P; Hammerschmid, F; Harrison, R; Hiestand, P; Jaksche, H; Mayer, P; Peichl, P

    1994-01-01

    (Me-Ile-4)cyclosporin (SDZ NIM 811) is a 4-substituted cyclosporin which is devoid of immunosuppressive activity but retains full capacity for binding to cyclophilin and exhibits potent anti-human immunodeficiency virus type 1 (HIV-1) activity. SDZ NIM 811 selectively inhibits HIV-1 replication in T4 lymphocyte cell lines, in a monocytic cell line, and in HeLa T4 cells. Furthermore, its antiviral activity against laboratory strains and against clinical isolates from geographically distinct regions in primary T4 lymphocytes and in primary monocytes (50% inhibitory concentration = 0.011 to 0.057 micrograms/ml) was demonstrated. SDZ NIM 811 does not inhibit proviral gene expression or virus-specific enzyme functions, either free or bound to cyclophilin. The compound does not influence CD4 expression or inhibit fusion between virus-infected and uninfected cells. SDZ NIM 811 was, however, found to block formation of infectious particles from chronically infected cells. Oral administration to mice, rats, dogs, and monkeys resulted in levels in blood considerably exceeding the drug concentration, which completely blocked virus replication in primary cells. SDZ NIM 811 caused changes of toxicity parameters in rats to a smaller degree than cyclosporine (formerly cyclosporin A). Thus, the potent and selective anti-HIV-1 activity of SDZ NIM 811 and its favorable pharmacokinetic behavior together with its lower nephrotoxicity than that of cyclosporine make this compound a promising candidate for development as an anti-HIV drug. PMID:7527198

  6. Analysis of human and primate CD2 molecules by protein sequence and epitope mapping with anti-human CD2 antibodies

    Microsoft Academic Search

    Melissa M Damschroder; Alexander A Kozhich; Robert M Woods; Li Cheng; Brian A Mullikin; Susan D Wilson; Nancy D Ulbrandt; Christine M Bachy; Herren Wu; JoAnn A Suzich; Peter A Kiener; William F Dall’Acqua; Wendy I White

    2004-01-01

    A panel of anti-human CD2 monoclonal antibodies (mAb) and soluble human CD58 (LFA-3) were tested for binding to human peripheral blood mononuclear cells (PBMCs), recombinant human CD2 and mononuclear cells from Cynomolgus, Rhesus and African green monkey, Stump-tail, Pig-tail and Assamese macaque, Chimpanzee and Baboon. This analysis revealed that whilst some antibodies recognized all species, there were differential binding profiles

  7. Marketed nonsteroidal anti-inflammatory agents, antihypertensives, and human immunodeficiency virus protease inhibitors: as-yet-unused weapons of the oncologists’ arsenal

    PubMed Central

    Papanagnou, Panagiota; Baltopoulos, Panagiotis; Tsironi, Maria

    2015-01-01

    Experimental data indicate that several pharmacological agents that have long been used for the management of various diseases unrelated to cancer exhibit profound in vitro and in vivo anticancer activity. This is of major clinical importance, since it would possibly aid in reassessing the therapeutic use of currently used agents for which clinicians already have experience. Further, this would obviate the time-consuming process required for the development and the approval of novel antineoplastic drugs. Herein, both pre-clinical and clinical data concerning the antineoplastic function of distinct commercially available pharmacological agents that are not currently used in the field of oncology, ie, nonsteroidal anti-inflammatory drugs, antihypertensive agents, and anti-human immunodeficiency virus agents inhibiting viral protease, are reviewed. The aim is to provide integrated information regarding not only the molecular basis of the antitumor function of these agents but also the applicability of the reevaluation of their therapeutic range in the clinical setting.

  8. Cetuximab in combination with anti-human IgG antibodies efficiently down-regulates the EGF receptor by macropinocytosis

    SciTech Connect

    Berger, Christian [Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway)] [Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway); Madshus, Inger Helene [Institute of Pathology, University of Oslo, Rikshospitalet, 0027 Oslo (Norway) [Institute of Pathology, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway); Stang, Espen, E-mail: espsta@rr-research.no [Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway)] [Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway)

    2012-12-10

    The monoclonal antibody C225 (Cetuximab) blocks binding of ligand to the epidermal growth factor receptor (EGFR). In addition, it is known that incubation with C225 induces endocytosis of the EGFR. This endocytosis has previously been shown to be increased when C225 is combined with an additional monoclonal anti-EGFR antibody. However, the effects of antibody combinations on EGFR activation, endocytosis, trafficking and degradation have been unclear. By binding a secondary antibody to the C225-EGFR complex, we here demonstrate that a combination of antibodies can efficiently internalize and degrade the EGFR. Although the combination of antibodies activated the EGFR kinase and induced ubiquitination of the EGFR, the kinase activity was not required for internalization of the EGFR. In contrast to EGF-induced EGFR down-regulation, the antibody combination efficiently degraded the EGFR without initiating downstream proliferative signaling. The antibody-induced internalization of EGFR was found not to depend on clathrin and/or dynamin, but depended on actin polymerization, suggesting induction of macropinocytosis. Macropinocytosis may cause internalization of large membrane areas, and this could explain the highly efficient internalization of the EGFR induced by combination of antibodies. -- Highlight: Black-Right-Pointing-Pointer Cetuximab induced endocytosis of EGFR increases upon combination with anti-human IgG. Black-Right-Pointing-Pointer Antibody combination causes internalization of EGFR by macropinocytosis. Black-Right-Pointing-Pointer Antibody-induced internalization of EGFR is independent of EGFR kinase activity. Black-Right-Pointing-Pointer Antibody combination may have a zipper effect and cross-link EGFRs on neighboring cells.

  9. Radiosensitive Severe Combined Immunodeficiency Disease

    PubMed Central

    Dvorak, Christopher C.; Cowan, Morton J.

    2009-01-01

    Synopsis Inherited defects in components of the non-homologous end joining DNA repair mechanism produce a T-B-NK+ severe combined immunodeficiency disease (SCID) characterized by heightened sensitivity to ionizing radiation. Patients with the radiosensitive form of SCID may also have increased short- and long-term sensitivity to the alkylator-based chemotherapy regimens traditionally utilized for conditioning prior to allogeneic hematopoietic cell transplantation (HCT). Known etiologies of radiosensitive SCID include deficiencies of Artemis, DNA Ligase IV, DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and Cernunnos-XLF, all of which have been treated with HCT. Because of their sensitivity to certain forms of chemotherapy, the approach to donor selection and type of conditioning regimen utilized for a radiosensitive SCID patient requires careful consideration. Significantly more research needs to be done in order to determine the long-term outcomes of radiosensitive SCID patients following HCT, as well as to discover novel non-toxic approaches to HCT that might benefit those with intrinsic radio- and chemo-sensitivity, as well as potentially all patients undergoing an HCT. PMID:20113890

  10. Frequent Transmission of Immunodeficiency Viruses among Bobcats and Pumas

    Microsoft Academic Search

    S. P. Franklin; J. L. Troyer; J. A. Terwee; L. M. Lyren; W. M. Boyce; S. P. D. Riley; M. E. Roelke; K. R. Crooks; S. VandeWoude

    2007-01-01

    With the exception of human immunodeficiency virus (HIV), which emerged in humans after cross-species transmissions of simian immunodeficiency viruses from nonhuman primates, immunodeficiency viruses of the family Lentiviridae represent species-specific viruses that rarely cross species barriers to infect new hosts. Among the Felidae, numerous immunodeficiency-like lentiviruses have been documented, but only a few cross-species transmissions have been recorded, and these

  11. Vaginal infections in human immunodeficiency virus–infected women

    Microsoft Academic Search

    Andrew Helfgott; Nancy Eriksen; C. Michael Bundrick; Ronald Lorimor; Barbara Van Eckhout

    2000-01-01

    Objective: This study was undertaken to compare the frequencies of vaginal infections among human immunodeficiency virus–infected women with those among human immunodeficiency virus–seronegative women. Study Design: Human immunodeficiency virus–seropositive women attending a comprehensive care center for human immunodeficiency virus disease at the outpatient department of an inner-city hospital in Houston underwent rigorous gynecologic evaluation for sexually transmitted diseases, including evidence

  12. IDR: the ImmunoDeficiency Resource

    PubMed Central

    Väliaho, Jouni; Pusa, Marianne; Ylinen, Tuomo; Vihinen, Mauno

    2002-01-01

    The ImmunoDeficiency Resource (IDR), freely available at http://www.uta.fi/imt/bioinfo/idr/, is a comprehensive knowledge base on immunodeficiencies. It is designed for different user groups such as researchers, physicians and nurses as well as patients and their families and the general public. Information on immunodeficiencies is stored as fact files, which are disease- and gene-based information resources. We have developed an inherited disease markup language (IDML) data model, which is designed for storing disease- and gene-specific data in extensible markup language (XML) format. The fact files written by the IDML can be used to present data in different contexts and platforms. All the information in the IDR is validated by expert curators. PMID:11752302

  13. Molecular evolution of primate immunodeficiency viruses and hepatitis delta virus

    Microsoft Academic Search

    Julia Samuilovna Krushkal

    1996-01-01

    Primate immunodeficiency viruses, or lentiviruses (HIV-1, HIV-2, and SIV), and hepatitis delta virus (HDV) are RNA viruses characterized by rapid evolution. Infection by primate immunodeficiency viruses usually results in the development of acquired immunodeficiency syndrome (AIDS) in humans and AIDS-like illnesses in Asian macaques. Similarly, hepatitis delta virus infection causes hepatitis and liver cancer in humans. These viruses are heterogeneous

  14. A CMA position. Acquired immunodeficiency syndrome.

    PubMed Central

    1989-01-01

    The following general principles serve as guidelines for various bodies, health care professionals and the general public. Specific aspects of infection with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) that relate to physicians' ethical responsibilities as well as society's moral obligations are discussed. Such matters include the need for education, research and treatment resources; the patient's right to investigation and treatment and to refusal of either; the need to obtain the patient's informed consent; the right to privacy and confidentiality; the importance of infection control; and the right to financial compensation in the case of occupational exposure to HIV. PMID:2909275

  15. [Acute polyradiculoneuritis and acquired immunodeficiency virus].

    PubMed

    Scaff, M; Rabello, G D; Marchiori, P E

    1989-03-01

    A 50-year-old man with positive test for human immunodeficiency virus (HIV) by enzyme-linked-immunoassy and Western-blot, without clinical manifestations of acquired immunodeficiency syndrome (AIDS), developed acute polyradiculoneuritis and was treated by plasmapheresis with improvement. We believe that chemical homologies of antigenic determinants between HIV and P2 protein of peripheral nervous system and myelin basic protein may induce crossed-reaction, thus developing acute polyradiculoneuritis and central nervous system involvement, respectively. The nervous system involvement hy HIV also occur in the HI-viremy, seric conversion alone, and AIDS with or without oportunistic infections. PMID:2764748

  16. Retrovirus-induced Immunodeficiency and Cancer

    Microsoft Academic Search

    Laura S. Levy

    \\u000a Malignant disease represents a major complication of human immunodeficiency virus-1 (HIV)-induced immunodeficiency in the\\u000a setting of AIDS. Three cancers have been identified as AIDS-defining conditions, including Kaposi’s sarcoma, non-Hodgkin’s\\u000a lymphomas, and invasive cervical carcinoma. In addition, classical Hodgkin’s lymphoma, anal cancer, and other cancers are\\u000a increased in incidence and\\/or severity in the context of HIV infection and AIDS. AIDS-associated malignancies

  17. Primary immunodeficiency diseases: a primer for PCPs.

    PubMed

    Younger, Elizabeth M; Epland, Kristin; Zampelli, Annette; Hintermeyer, Mary K

    2015-02-15

    Primary care providers (PCPs) play a key role in identifying patients with primary immunodeficiency diseases (PIDDs). This diagnosis has implications for PCPs, as patients continue to require primary care and management after a PIDD diagnosis has been made. This review presents essential information for PCPs regarding PIDDs. PMID:25594294

  18. Cardiac sequelae of human immunodeficiency virus disease.

    PubMed

    Alqaqa, Ashraf; Suleiman, Addi; Birnhak, Stefani; Tariq, Saad; Sison, Raymund; Hamdan, Aiman; DeBari, Vincent A; Shamoon, Fayez

    2014-07-01

    Presently, patients with human immunodeficiency virus infection are living longer and are frequently encountered in medical practice. HIV infection is a systemic disease, which affects a wide spectrum of organs. Cardiac involvement is frequent, and the consequent clinical manifestations are a common reason to seek medical advice. In this review, we discuss the different cardiac sequelae of HIV infection. PMID:24743404

  19. Pathogenic Simian Immunodeficiency Virus Infection Is Associated

    E-print Network

    Wang, David

    -level tax- onomy of enteric bacteria was detected. Thus, enteric viral infections may contribute to AIDS enPathogenic Simian Immunodeficiency Virus Infection Is Associated with Expansion of the Enteric candidate etiologies for AIDS enteropathy, we used next-generation sequencing to define the enteric virome

  20. Early diagnosis of severe combined immunodeficiency syndrome

    Microsoft Academic Search

    R A Hague; S Rassam; G Morgan; A J Cant

    1994-01-01

    Infants with severe combined immunodeficiency syndrome (SCIDS) have a greatly improved prognosis if diagnosed and treated before they develop overwhelming infection. Clinical and laboratory data on 45 patients with SCIDS were retrospectively reviewed to assess the value of absolute lymphocyte counts in making an early diagnosis. Ninety infants matched for age, sex, and presenting symptoms were used as controls. Thirteen

  1. Human Immunodeficiency Virus and Carcinoma Cervix

    Microsoft Academic Search

    A. Jaisri; Shanta Bhaskaran; Prasanna Kumar

    2010-01-01

    Problem statement: Carcinoma of the cervix is the second leading cause of death in women in the world. Human Papilloma Virus (HPV) which plays a major role in the etiology of cervical cancer is said to have the same mode of transmission as the H uman Immunodeficiency Virus (HIV). Hence the curiosity to learn the prevalence, incidence and as sociation

  2. Simultaneous quartz crystal microbalance-electrochemical impedance spectroscopy study on the adsorption of anti-human immunoglobulin G and its immunoreaction at nanomaterial-modified Au electrode surfaces.

    PubMed

    Jia, Xueen; Xie, Qingji; Zhang, Youyu; Yao, Shouzhuo

    2007-06-01

    The quartz crystal microbalance method (QCM), in combination with electrochemical impedance spectroscopy (EIS), has been utilized to monitor in situ anti-human IgG adsorption on several Au-based surfaces, bare Au, nanogold/4-aminothiophenol (4AT)/Au, and multi-walled carbon nanotubes (MWCNT)/Au, and succeeding human IgG reactions. Also, the immobilization protocol of anti-human IgG via its glutaraldehyde (GA) cross-linking with self-assembled 4AT on an Au electrode and the subsequent surface immunoreaction were examined. The resonant frequency (f(0)) and the motional resistance (R(1)) of the piezoelectric quartz crystal (PQC) as well as electrochemical impedance parameters were measured and discussed. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) of the ferricyanide/ferrocyanide couple were examined before and after electrode modification, the antibody adsorption and antibody-antigen reactions. We found that the amount for antibody adsorption was the greatest on the colloid Au modified surface, and that at MWCNT ranked the second, while specific bioactivity was almost identical on the four kinds of surfaces. Two parameters simultaneously obtained at the colloid Au modified surface, Deltaf(0) and DeltaC(s) (interfacial capacitance), have been used to estimate the association constant of the immunoreaction. PMID:17575353

  3. Anti-human IG and B lymphocytes reconstitute the proliferative response to Con A of T lymphocytes depleted of accessory cells

    SciTech Connect

    Tsuda, T.; Kim, Y.T.; Schwab, R.; Siskind, G.W.; Weksler, M.E.

    1986-03-01

    The requirements for the induction of proliferation of human peripheral blood mononuclear cells (PBM) by low concentrations of Concanavalin A (Con A) were studied using /sup 3/H-thymidine incorporation to assay DNA synthesis. Removal of plastic-adherent cells from PBM reduced the proliferative response of lymphocytes to Con A by 80%. Passage of these cells over nylon wool columns totally eliminated their response to Con A. Addition of adherent monocytes or rabbit anti-human IgG conjugated to polyacrylamide beads (anti-IgG beads) to the non-adherent lymphocyte population reconstituted the proliferative response. The lymphoblasts activated in these cultures were more than 90% T11 positive. Anti-IgG beads did not activate lymphocyte proliferation in the absence of Con A. The response of non-adherent lymphocytes to Con A could also be reconstituted by unconjugated rabbit anti-human IgG antiserium. Purified T cells could only be activated by anti-IgG beads and low concentrations of Con A in the presence of irradiated B cells. These results suggest that /sup 3/H-thymidine incorporation by T cells induced by anti-IgG beads and a low concentration of Con A depends on the interaction of anti-IgG and B cells. The authors suggest that B cell produce growth factors for T cells after interacting with anti-IgG.

  4. Modeling a safer smallpox vaccination regimen, for human immunodeficiency virus type 1-infected patients, in immunocompromised macaques.

    PubMed

    Edghill-Smith, Yvette; Venzon, David; Karpova, Tatiana; McNally, James; Nacsa, Janos; Tsai, Wen-Po; Tryniszewska, Elzbieta; Moniuszko, Marcin; Manischewitz, Jody; King, Lisa R; Snodgrass, Steven J; Parrish, John; Markham, Phil; Sowers, Marsha; Martin, Derrick; Lewis, Mark G; Berzofsky, Jay A; Belyakov, Igor M; Moss, Bernard; Tartaglia, Jim; Bray, Mike; Hirsch, Vanessa; Golding, Hana; Franchini, Genoveffa

    2003-10-15

    We have modeled smallpox vaccination with Dryvax (Wyeth) in rhesus macaques that had depletion of CD4(+) T cells induced by infection with simian immunodeficiency virus or simian/human immunodeficiency virus. Smallpox vaccination induced significantly larger skin lesions in immunocompromised macaques than in healthy macaques. Unexpectedly, "progressive vaccinia" was infrequent. Vaccination of immunocompromised macaques with the genetically-engineered, replication-deficient poxvirus NYVAC, before or after retrovirus infection, was safe and lessened the severity of Dryvax-induced skin lesions. Neutralizing antibodies to vaccinia were induced by NYVAC, even in macaques with severe CD4(+) T cell depletion, and their titers inversely correlated with the time to complete resolution of the skin lesions. Together, these results provide the proof of concept, in macaque models that mirror human immunodeficiency virus type 1 infection, that a prime-boost approach with a highly attenuated poxvirus followed by Dryvax increases the safety of smallpox vaccination, and they highlight the importance of neutralizing antibodies in protection against virulent poxvirus. PMID:14551889

  5. Adeno-Associated Virus 9-Mediated Airway Expression of Antibody Protects Old and Immunodeficient Mice against Influenza Virus

    PubMed Central

    Adam, Virginie S.; Crosariol, Marco; Kumar, Sachin; Ge, Moyar Q.; Czack, Sarah E.; Roy, Soumitra; Haczku, Angela; Tretiakova, Anna; Wilson, James M.

    2014-01-01

    Influenza causes serious and sometimes fatal disease in individuals at risk due to advanced age or immunodeficiencies. Despite progress in the development of seasonal influenza vaccines, vaccine efficacy in elderly and immunocompromised individuals remains low. We recently developed a passive immunization strategy using an adeno-associated virus (AAV) vector to deliver a neutralizing anti-influenza antibody at the site of infection, the nasal airways. Here we show that young, old, and immunodeficient (severe combined immunodeficient [SCID]) mice that were treated intranasally with AAV9 vector expressing a modified version of the broadly neutralizing anti-influenza antibody FI6 were protected and exhibited no signs of disease following an intranasal challenge with the mouse-adapted H1N1 influenza strain A/Puerto Rico/8/1934(H1N1) (PR8) (Mt. Sinai strain). Nonvaccinated mice succumbed to the PR8 challenge due to severe weight loss. We propose that airway-directed AAV9 passive immunization against airborne infectious agents may be beneficial in elderly and immunocompromised patients, for whom there still exists an unmet need for effective vaccination against influenza. PMID:25209558

  6. In vitro comparison of topical microbicides for prevention of human immunodeficiency virus type 1 transmission.

    PubMed

    Dezzutti, Charlene S; James, V Nicole; Ramos, Artur; Sullivan, Sharon T; Siddig, Aladin; Bush, Timothy J; Grohskopf, Lisa A; Paxton, Lynn; Subbarao, Shambavi; Hart, Clyde E

    2004-10-01

    A standardized protocol was used to compare cellular toxicities and anti-human immunodeficiency virus type 1 (HIV-1) activities of candidate microbicides formulated for human use. The microbicides evaluated were cellulose acetate phthalate (CAP), Carraguard, K-Y plus nonoxynol-9 (KY-N9), PRO 2000 (0.5 and 4%), SPL7013 (5%), UC781 (0.1 and 1%), and Vena Gel, along with their accompanying placebos. Products were evaluated for toxicity on cervical and colorectal epithelial cell lines, peripheral blood mononuclear cells (PBMCs), and macrophages (MPhi) by using an ATP release assay, and they were tested for their effect on transepithelial resistance (TER) of polarized epithelial monolayers. Anti-HIV-1 activity was evaluated in assays for transfer of infectious HIV-1 from epithelial cells to activated PBMCs and for PBMC and MPhi infection. CAP, Carraguard, PRO 2000, SPL7013, and UC781 along with their placebos were 20- to 50-fold less toxic than KY-N9 and Vena Gel. None of the nontoxic product concentrations disrupted the TER. Transfer of HIV-1(Ba-L) from epithelial cells to PBMCs and PBMC and MPhi infection with laboratory-adapted HIV-1(Ba-L) and HIV-1(LAI) isolates were inhibited by all products except Carraguard, KY-N9, and Vena Gel. KY-N9, Vena Gel, and Carraguard were not effective in blocking PBMC infection with primary HIV-1(A), HIV-1(C), and HIV-1(CRF01-AE) isolates. The concordance of these toxicity results with those previously reported indicates that our protocol may be useful for predicting toxicity in vivo. Moreover, our systematic anti-HIV-1 testing provides a rational basis for making better informed decisions about which products to consider for clinical trials. PMID:15388443

  7. Identification of a Subset of Common Variable Immunodeficiency Patients with Impaired B-Cell Protein Tyrosine Phosphorylation

    PubMed Central

    Schwartz, Rivka; Porat, Yael Ben-Anat; Handzel, Zeev; Sthoeger, Zeev; Garty, Ben-Zion; Confino-Cohen, Ronit; Levy, Jacov; Zan-Bar, Israel

    1999-01-01

    The mechanisms responsible for common variable immunodeficiency syndrome (CVID) are as yet unknown. In the present study, we show that the B-cell dysfunction in a subset of CVID patients is caused by defective protein tyrosine phosphorylation (PTP). We demonstrated that the PTP level and immunoglobulin (Ig) secretion malfunctions can be successfully repaired when normal plasma membrane components are implanted into these patients’ B cells. Stimulation of CVID patients’ peripheral blood mononucleated cells with anti-Ig antibody revealed that 7 of 11 patients had lower PTP levels than those found in the normal donor cells. Plasma membrane implantation to the cells of these patients resulted in elevated PTP levels which reached normal levels upon stimulation with anti-human Ig antibody. The results revealed two distinct groups of CVID patients. The first group included patients whose B cells expressed low PTP levels after Ig stimulation. In these patients the plasma membrane implantation restored the normal PTP level as well as the ability to secrete IgM and/or IgG after B-cell stimulation. In the second group, patients whose B cells expressed a normal PTP level after Ig stimulation, with no restoration of their ability to secrete Ig upon plasma membrane implantation and lipopolysaccharide stimulation. We conclude that the first group has an early signal transduction defect located in the B-cell plasma membrane, while in the second group the defect is located elsewhere. PMID:10548576

  8. Educational paper: syndromic forms of primary immunodeficiency.

    PubMed

    Kersseboom, Rogier; Brooks, Alice; Weemaes, Corry

    2011-03-01

    The syndromic primary immunodeficiencies are disorders in which not only the immune system but also other organ systems are affected. Other features most commonly involve the ectodermal, skeletal, nervous, and gastrointestinal systems. Key in identifying syndromic immunodeficiencies is the awareness that increased susceptibility to infections or immune dysregulation in a patient known to have other symptoms or special features may hint at an underlying genetic syndrome. Because the extraimmune clinical features can be highly variable, it is more difficult establishing the correct diagnosis. Nevertheless, correct diagnosis at an early age is important because of the possible treatment options. Therefore, diagnostic work-up is best performed in a center with extensive expertise in this field, having immunologists and clinical geneticists, as well as adequate support from a specialized laboratory at hand. This paper provides the general pediatrician with the main clinical features that are crucial for the recognition of these syndromes. PMID:21337117

  9. Organising pneumonia in common variable immunodeficiency

    PubMed Central

    Boujaoude, Ziad; Arya, Rohan; Rafferty, William; Dammert, Pedro

    2013-01-01

    Common variable immunodeficiency (CVID) is the most common of the primary immunodeficiency disorders. Pulmonary manifestations are characterised by recurrent rhinosinusitis, respiratory tract infections and bronchiectasis. Less commonly the lung may be affected by lymphoid disorders and sarcoid-like granulomas. Organising pneumonia (OP) is a rare pulmonary manifestation. We report the case of a 32-year-old woman with CVID who presented with fever, dyspnoea and persistent lung infiltrates despite antibiotic therapy. CT of the chest showed bilateral patchy alveolar infiltrates. Pulmonary function tests revealed moderate restriction and reduction in diffusion capacity. Initial bronchoscopy with transbronchial biopsies did not yield a diagnosis but surgical lung biopsies identified OP. Significant clinical, radiographic and physiological improvement was achieved after institution of corticosteroid therapy. PMID:23749855

  10. Cytokine-neutralizing therapeutic antibodies

    Microsoft Academic Search

    Amanda Suitters; Roly Foulkes

    \\u000a Monoclonal antibodies (Mabs) offer the potential as useful therapeutic agents because of their high affinity and selectivity\\u000a for the target antigen. The standard approach in making Mabs has been to immunise rodents, usually mice, with the desired\\u000a human protein and generate a mouse anti-human IgG through hybridoma technology. Indeed mouse Mabs are used clinically in acute\\u000a diseases, such as the

  11. Demonstration of antifungal and anti-human immunodeficiency virus reverse transcriptase activities of 6-methoxy-2-benzoxazolinone and antibacterial activity of the pineal indole 5-methoxyindole-3-acetic acid

    Microsoft Academic Search

    H. X Wang; T. B Ng

    2002-01-01

    6-Methoxy-2-benzoxazolinone (6-MBOA), a naturally occurring progonadal compound present in grasses with structural resemblance to melatonin, was tested for antifungal activity against Fusarium oxysporum, Rhizoctonia solani and Coprinus comatus. A variety of pineal products was also examined for the sake of comparison, including 5-methoxytryptamine, melatonin, 5-methoxytryptophol, 5-hydroxytryptamine, 5-methoxyindole-3-acetic acid and 5-hydroxytryptophol. The assay for antifungal activity was carried out in Petri

  12. Progressive vaccinia associated with combined variable immunodeficiency.

    PubMed

    Keane, J T; James, K; Blankenship, M L; Pearson, R W

    1983-05-01

    Progressive vaccinia developed in a previously healthy woman following smallpox vaccination and was successfully treated with vaccinia immune human globulin and methisazone. Immunologic evaluation over the next 4 1/2 years revealed evidence for combined variable immunodeficiency with increased numbers of circulating OKT 8 positive (suppressor-cytotoxic T) cells and the virtual absence of OKT 4 positive (helper-inducer T) cells. PMID:6847220

  13. Hypocomplementemia and Human Immunodeficiency Virus Infection

    Microsoft Academic Search

    Robert Y. Lin; Olga Wildfeuer; Monica M. Franklin; Kenneth Candido

    1988-01-01

    The levels of C4 and C3 were measured and related to other immunological and clinical parameters in 44 patients with the human immunodeficiency virus (HIV) infection. Circulating immune complexes (C1q-C?C) as measured by an enzyme-linked immunosorbent assay employing monoclonal antibody with specificity for bound C1q, and serum immunoglobulin G (IgG) concentrations were assessed simultaneously. Clinical parameters assessed included: (1) the

  14. Pharmacological Inhibition of Feline Immunodeficiency Virus (FIV)

    PubMed Central

    Mohammadi, Hakimeh; Bienzle, Dorothee

    2012-01-01

    Feline immunodeficiency virus (FIV) is a member of the retroviridae family of viruses and causes an acquired immunodeficiency syndrome (AIDS) in domestic and non-domestic cats worldwide. Genome organization of FIV and clinical characteristics of the disease caused by the virus are similar to those of human immunodeficiency virus (HIV). Both viruses infect T lymphocytes, monocytes and macrophages, and their replication cycle in infected cells is analogous. Due to marked similarity in genomic organization, virus structure, virus replication and disease pathogenesis of FIV and HIV, infection of cats with FIV is a useful tool to study and develop novel drugs and vaccines for HIV. Anti-retroviral drugs studied extensively in HIV infection have targeted different steps of the virus replication cycle: (1) inhibition of virus entry into susceptible cells at the level of attachment to host cell surface receptors and co-receptors; (2) inhibition of fusion of the virus membrane with the cell membrane; (3) blockade of reverse transcription of viral genomic RNA; (4) interruption of nuclear translocation and viral DNA integration into host genomes; (5) prevention of viral transcript processing and nuclear export; and (6) inhibition of virion assembly and maturation. Despite much success of anti-retroviral therapy slowing disease progression in people, similar therapy has not been thoroughly investigated in cats. In this article we review current pharmacological approaches and novel targets for anti-lentiviral therapy, and critically assess potentially suitable applications against FIV infection in cats. PMID:22754645

  15. Mycobacterial disease, immunosuppression, and acquired immunodeficiency syndrome.

    PubMed Central

    Collins, F M

    1989-01-01

    The mycobacteria are an important group of acid-fast pathogens ranging from obligate intracellular parasites such as Mycobacterium leprae to environmental species such as M. gordonae and M. fortuitum. The latter may behave as opportunistic human pathogens if the host defenses have been depleted in some manner. The number and severity of such infections have increased markedly with the emergence of the acquired immunodeficiency syndrome (AIDS) epidemic. These nontuberculous mycobacteria tend to be less virulent for humans than M. tuberculosis, usually giving rise to self-limiting infections involving the cervical and mesenteric lymph nodes of young children. However, the more virulent serovars of M. avium complex can colonize the bronchial and intestinal mucosal surfaces of healthy individuals, becoming virtual members of the commensal gut microflora and thus giving rise to low levels of skin hypersensitivity to tuberculins prepared from M. avium and M. intracellulare. Systemic disease develops when the normal T-cell-mediated defenses become depleted as a result of old age, cancer chemotherapy, or infection with human immunodeficiency virus. As many as 50% of human immunodeficiency virus antibody-positive individuals develop mycobacterial infections at some time during their disease. Most isolates of M. avium complex from AIDS patients fall into serotypes 4 and 8. The presence of these drug-resistant mycobacteria in the lungs of the AIDS patient makes their effective clinical treatment virtually impossible. More effective chemotherapeutic, prophylactic, and immunotherapeutic reagents are urgently needed to treat this rapidly increasing patient population. PMID:2680057

  16. Between detection and neutralization

    Microsoft Academic Search

    D. G. Adams; M. K. Snell; M. W. Green; Daniel Allison Pritchard

    2005-01-01

    Security system analytical performance analysis is generally based on the probability of system effectiveness. The probability of effectiveness is a function of the probabilities of interruption and neutralization. Interruption occurs if the response forces are notified in sufficient time to engage the adversary. Neutralization occurs if the adversary attack is defeated after the security forces have actively engaged the adversary.

  17. Neutralizing Acids and Bases

    NSDL National Science Digital Library

    2012-04-08

    Learners use their knowledge of color changes with red cabbage indicator to neutralize an acidic solution with a base and then neutralize a basic solution with an acid. Use this as a follow-up activity to the related activity, "Color Changes with Acids and Bases."

  18. Human immunodeficiency virus type 2: pathogenesis and antiretroviral therapy

    Microsoft Academic Search

    Ende van der M. E

    2000-01-01

    Human immunodeficiency virus type1 (HIV-1), human immunodeficiency\\u000avirus type 2 (HIV-2), and simian immunodeficiency virus (SIV) have been\\u000aidentified as hither unknown primate members of the Lentivirinae subfamily\\u000aof the family Retroviridae in 1983, 1986 and 1985 respectively, HIV-1 and\\u000aHIV-2 were identified as the causative agents of the newly emerging\\u000aacquired immunodeficiency syndrome (AIDS) of humans (1-3) and SIV

  19. Genetics Home Reference: Hepatic veno-occlusive disease with immunodeficiency

    MedlinePLUS

    ... Gene Reviews Clinical summary Genetic Testing Registry Genetic testing PubMed Recent literature OMIM Genetic disorder catalog Conditions > Hepatic veno-occlusive disease with immunodeficiency ( ...

  20. [Skin symptoms associated with human immunodeficiency virus infection].

    PubMed

    Tamási, Béla; Marschalkó, Márta; Kárpáti, Sarolta

    2015-01-01

    The recently observed accelerated increase of human immunodeficiency virus infection in Hungary poses a major public concern for the healthcare system. Given the effective only but not the curative therapy, prevention should be emphasized. Current statistics estimate that about 50% of the infected persons are not aware of their human immunodeficiency virus-positivity. Thus, early diagnosis of the infection by serological screening and timely recognition of the disease-associated symptoms are crucial. The authors' intention is to facilitate early infection detection with this review on human immunodeficiency virus-associated skin symptoms, and highlight the significance of human immunodeficiency virus care in the everyday medical practice. PMID:25544049

  1. Changes in the Immunogenic Properties of Soluble gp140 Human Immunodeficiency Virus Envelope Constructs upon Partial Deletion of the Second Hypervariable Region

    Microsoft Academic Search

    Indresh K. Srivastava; Keating VanDorsten; Lucia Vojtech; Susan W. Barnett; Leonidas Stamatatos

    2003-01-01

    Immunization of macaques with the soluble oligomeric gp140 form of the SF162 envelope (SF162gp140) or with an SF162gp140-derived construct lacking the central region of the V2 loop (V2gp140) results in the generation of high titers of antibodies capable of neutralizing the homologous human immunodeficiency virus type 1 (HIV-1), SF162 virus (Barnett et al. J. Virol. 75:5526-5540, 2001). However, the V2gp140

  2. Human Immunodeficiency Virus and Acquired Immunodeficiency Syndrome: Correlation but not Causation

    Microsoft Academic Search

    Peter H. Duesberg

    1989-01-01

    AIDS is an acquired immunodeficiency syndrome defined by a severe depletion of T cells and over 20 conventional degenerative and neoplastic diseases. In the U.S. and Europe, AIDS correlates to 95% with risk factors, such as about 8 years of promiscuous male homosexuality, intravenous drug use, or hemophilia. Since AIDS also correlates with antibody to a retrovirus, confirmed in about

  3. Human Immunodeficiency Virus and Acquired Immunodeficiency Syndrome: Correlation but not Causation

    Microsoft Academic Search

    Peter H. Duesberg

    1989-01-01

    AIDS is an acquired immunodeficiency syndrome defined by a severe depletion of T cells and over 20 conventional degenerative and neoplastic diseas es. In the U.S. and Europe, AIDS correlates to 95% with risk factors, such as about 8 years of promiscuous male homosexuality, intravenous drug use, or hemophilia. Since AIDS also correlates with antibody to a retrovirus, confirmed in

  4. Chimeric Plant Virus Particles as Immunogens for Inducing Murine and Human Immune Responses against Human Immunodeficiency Virus Type 1

    PubMed Central

    Marusic, Carla; Rizza, Paola; Lattanzi, Laura; Mancini, Camillo; Spada, Massimo; Belardelli, Filippo; Benvenuto, Eugenio; Capone, Imerio

    2001-01-01

    The high-yield expression of a neutralizing epitope from human immunodeficiency virus type 1 (HIV-1) on the surface of a plant virus and its immunogenicity are presented. The highly conserved ELDKWA epitope from glycoprotein (gp) 41 was expressed as an N-terminal translational fusion with the potato virus X (PVX) coat protein. The resulting chimeric virus particles (CVPs), purified and used to immunize mice intraperitoneally or intranasally, were able to elicit high levels of HIV-1-specific immunoglobulin G (IgG) and IgA antibodies. Furthermore, the human immune response to CVPs was studied with severe combined immunodeficient mice reconstituted with human peripheral blood lymphocytes (hu-PBL-SCID). hu-PBL-SCID mice immunized with CVP-pulsed autologous dendritic cells were able to mount a specific human primary antibody response against the gp41-derived epitope. Notably, sera from both normal and hu-PBL-SCID mice showed an anti-HIV-1-neutralizing activity. Thus, PVX-based CVPs carrying neutralizing epitopes can offer novel perspectives for the development of effective vaccines against HIV and, more generally, for the design of new vaccination strategies in humans. PMID:11507188

  5. Long-term memory B-cell responses in recipients of candidate human immunodeficiency virus type 1 vaccines.

    PubMed

    Evans, Thomas G; Frey, Sharon; Israel, Heidi; Chiu, Joseph; El-Habib, Raphaelle; Gilbert, Peter; Gaitan, Alicia; Montefiori, David C

    2004-06-30

    The efficacy and practical application of human immunodeficiency virus type 1 (HIV-1) vaccines may depend in part on the longevity of the immune responses generated, particularly those in the memory compartment. Candidate vaccines based on the HIV-1 envelope glycoproteins generate binding and neutralizing antibodies in humans but there have been no prior studies on the long-term persistence and recall of those responses. We evaluated six healthy, HIV non-infected adults who had received a combination of recombinant canarypox HIV-1 vaccines boosted by gp120 and who had achieved a high serum titer of neutralizing antibody to HIV-1 MN. These individuals were administered a gp160 boost 4-5 years after their last vaccination. Four volunteers had detectable binding and neutralizing antibodies at the time of boosting and all six volunteers exhibited a recall binding and neutralizing antibody response. The antibodies neutralized multiple T cell line-adapted (TCLA) strains of virus, including the vaccine strain, but not primary isolates. These results demonstrate that memory B-cell responses can last for many years following HIV-1 envelope glycoprotein immunization. In principle, similar long-term memory may be possible with improved immunogens that generate broadly cross-reactive neutralizing antibodies. PMID:15193388

  6. Immunodeficiency, centromeric region instability, facial anomalies syndrome (ICF)

    Microsoft Academic Search

    Melanie Ehrlich; Kelly Jackson; Corry Weemaes

    2006-01-01

    The Immunodeficiency, Centromeric region instability, Facial anomalies syndrome (ICF) is a rare autosomal recessive disease described in about 50 patients worldwide and characterized by immunodeficiency, although B cells are present, and by characteristic rearrangements in the vicinity of the centromeres (the juxtacentromeric heterochromatin) of chromosomes 1 and 16 and sometimes 9. Other variable symptoms of this probably under-diagnosed syndrome include

  7. Revisiting the role of neutralizing antibodies in mother-to-child transmission of HIV-1.

    PubMed

    Barin, Francis; Jourdain, Gonzague; Brunet, Sylvie; Ngo-Giang-Huong, Nicole; Weerawatgoompa, Supawadee; Karnchanamayul, Warit; Ariyadej, Surabhon; Hansudewechakul, Rawiwan; Achalapong, Jullapong; Yuthavisuthi, Prapap; Ngampiyaskul, Chaiwat; Bhakeecheep, Sorakij; Hemwutthiphan, Chittaphon; Lallemant, Marc

    2006-06-01

    We analyzed the association between mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) and maternal neutralizing antibodies to heterologous primary isolates of various HIV-1 clades, to test the hypothesis that protective antibodies are those with broad neutralizing activity. Our study sample included 90 Thai women for whom the timing of HIV-1 transmission (in utero or intrapartum) was known. The statistical analysis included a conditional logistic-regression model to control for both plasma viral load and duration of zidovudine prophylaxis. The higher the titer of neutralizing antibodies to a heterologous strain of the same clade, the lower the rate of MTCT of HIV-1. More specifically, high levels of neutralizing antibodies to the MBA (CRF01_AE) strain were associated with low intrapartum transmission of HIV-1. This suggested that such heterologous neutralizing antibodies may be involved in the natural prevention of late perinatal HIV transmission. These data are consistent with the hypothesis that the use of some antibodies might help to prevent perinatal HIV transmission, through passive immunoprophylaxis. Moreover, the study of humoral factors associated with MTCT of HIV-1 may identify correlates of protection that should help in the design of efficient HIV/acquired immunodeficiency syndrome vaccines. PMID:16652277

  8. Human\\/mouse radiation chimera generated from PBMC of B chronic lymphocytic leukemia patients with autoimmune hemolytic anemia produce anti-human red cell antibodies

    Microsoft Academic Search

    H Marcus; A Shimoni; D Ergas; A Canaan; B Dekel; D Ben-David; M David; E Sigler; Y Reisner; A Berrebi

    1997-01-01

    Previous studies performed in our laboratory have shown that B-CLL cells are involved in the production of anti-red cell auto-antibodies, providing a possible mechanism for the auto-immune hemolytic anemia occurring during the course of B-CLL. In order to confirm this hypothesis, we attempted to transfer human B-CLL with AIHA to immunodeficient mice. Peripheral blood mononuclear cells (PBMC) from 11 B-CLL

  9. Humoral Primary Immunodeficiencies in Chronic Rhinosinusitis.

    PubMed

    Nayan, Smriti; Alizadehfar, Reza; Desrosiers, Martin

    2015-08-01

    Chronic rhinosinusitis (CRS) may be the primary presenting symptom for primary immunodeficiencies (PID). PID can affect the humoral or the cellular immune system. This paper provides an overview of PID which affect the humoral immune system, with details around the diagnostic criteria, the epidemiology, the subtypes, the clinical manifestations, underlying molecular mechanisms, methods to screen for PID and the management of CRS in the context of PID. A high clinical suspicion of PID is required when assessing patients with CRS who are refractory to maximal medical therapy. PMID:26149586

  10. Health Administrator Perspectives on Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Prevention and Services at Historically Black Colleges and Universities

    ERIC Educational Resources Information Center

    Warren-Jeanpiere, Lari; Jones, Sandra; Sutton, Madeline Y.

    2011-01-01

    Objective: Due to the disproportionate impact of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) among African American young adults, the authors explored (1) number of historically black college and university (HBCU) campuses with existing HIV prevention policies and services and (2) perceived barriers for implementing…

  11. Neonatal Screening for Severe Combined Immunodeficiency (SCID)

    PubMed Central

    Puck, Jennifer M.

    2012-01-01

    Purpose of review Population-based newborn screening for severe combined immunodeficiency (SCID) and related disorders has been instituted in five states, with several more planning to add this testing to their newborn screening panels. This review summarizes the rationale, development, and implementation of SCID screening programs to date and highlights current and future challenges. Recent findings Early results of T-cell receptor excision circle (TREC) testing newborns in pilot states indicate that this addition to the newborn screening panel can be successfully integrated into state public health programs. The TREC test has clinical validity and TRECs, as predicted, are an excellent biomarker of poor T-cell lymphocyte production in the thymus or increased lymphocyte loss resulting in T-cell lymphopenia. A variety of cases with typical SCID genotypes and other conditions have been detected in a timely manner and referred for appropriate early treatment. Summary Early detection of primary immunodeficiency is recognized as important for avoiding infectious complications that compromise outcomes. Routine screening of all newborns with the TREC test, implemented as part of an integrated public health program, can achieve pre-symptomatic diagnosis of SCID and other disorders with T-cell lymphopenia, allowing prompt and effective treatment and leading to a better understanding of the spectrum of these disorders and how to manage them. PMID:22001765

  12. Human immunodeficiency virus infection in Haiti.

    PubMed Central

    Pierre, J. A.; Fournier, A. M.

    1999-01-01

    This article reviews human immunodeficiency virus (HIV) infection in Haiti. The evolution of the epidemic in Haiti, its spread from urban to rural areas, its varied clinical manifestations, and the attitudes of Haitian people toward HIV infection provide important lessons on understanding and managing this infection in a developing country. The heterosexual spread of HIV, particularly among the poor, is well-documented as is the role of other sexually transmitted diseases along with tuberculosis. Coinfection of HIV and tuberculosis have led researchers to study the effects of six-month supervised intermittent tuberculosis therapy both in controlling tuberculosis and slowing the progression of HIV. Various surveys and discussion groups about acquired immunodeficiency virus knowledge and beliefs demonstrate a large deficit in HIV education despite campaigns to educate the population. The great impact of HIV disease on morbidity and mortality in Haiti indicates that a great deal of work still needs to be accomplished and demonstrates the frustration in fighting the infection in countries with inadequate resources and infrastructure. Advances in HIV vaccine research seem to be the most promising option for developing countries such as Haiti. PMID:10203919

  13. Immunogenicity of virus-like particles containing modified human immunodeficiency virus envelope proteins

    PubMed Central

    Quan, Fu-Shi; Sailaja, Gangadhara; Skountzou, Ioanna; Huang, Chunzi; Vzorov, Andrei; Compans, Richard W.; Kang, Sang-Moo

    2007-01-01

    Extensive glycosylation and variable loops of the HIV envelope protein (Env) are reported to shield some neutralizing epitopes. Here, we investigated the immunogenicity of mutated HIV Envs presented in virus-like particles (VLPs). We immunized mice with simian human immunodeficiency virus (SHIV) VLPs containing mutant HIV Env with reduced glycosylation (3G), variable loop-deleted mutations (dV1V2), or combinations of both types of mutations (3G-dV2?1G), and evaluated immune responses. Immune sera from mice that received VLPs with modified HIV Envs (3G or dV1V2) showed higher neutralizing activities against the homologous HIV 89.6 virus as well as heterologous viruses when compared with wild type SHIV VLP-immunized mice. Lymphocytes from immunized mice produced HIV Env-specific cytokines, with the 3G-dV2?1G mutant producing high levels of cytokines. Interestingly, both dendritic cells and B cells were found to interact with VLPs suggesting that VLPs are effective immunogens. Therefore, this study suggests that VLPs containing modified HIV Env have the potential to be developed as candidate vaccines capable of inducing cellular and humoral immune responses including neutralizing activities. PMID:17320250

  14. The Neutral Medium

    E-print Network

    Robert Braun

    2005-01-17

    We consider the physical conditions of the neutral medium within, and in the environments of, galaxies. The basic physical and morphological properties of the neutral medium within galaxy disks are now quite well-constrained. Systematic variations in temperature and phase-balance (of cool versus warm neutral gas) are indicated as a function of both radius and z-height. Interestingly, the cool medium line-widths are observed to be dominated by turbulent energy injection within cells of 10 pc to 1 kpc size. Deep new observations reveal that 5-10% of the neutral medium is associated within an extended halo which rotates more slowly and experiences radial inflow. Much of this component is likely to be associated with a ``galactic fountain'' type of phenomenon. However, compelling evidence is also accumulating for the importance of tidal disruption of satellites as well as continuous accretion (of both diffuse and discrete components) in fueling galaxy halos and disks. Continued fueling is even observed on scales of 100's of kpc in galaxy environments, where the neutral component is likely to be merely a trace constituent of a highly ionized plasma.

  15. C-terminal tail of human immunodeficiency virus gp41: functionally rich and structurally enigmatic

    PubMed Central

    Steckbeck, Jonathan D.; Kuhlmann, Anne-Sophie

    2013-01-01

    The human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) pandemic is amongst the most important current worldwide public health threats. While much research has been focused on AIDS vaccines that target the surface viral envelope (Env) protein, including gp120 and the gp41 ectodomain, the C-terminal tail (CTT) of gp41 has received relatively little attention. Despite early studies highlighting the immunogenicity of a particular CTT sequence, the CTT has been classically portrayed as a type I membrane protein limited to functioning in Env trafficking and virion incorporation. Recent studies demonstrate, however, that the Env CTT has other important functions. The CTT has been shown to additionally modulate Env ectodomain structure on the cell and virion surface, affect Env reactivity and viral sensitivity to conformation-dependent neutralizing antibodies, and alter cell–cell and virus–cell fusogenicity of Env. This review provides an overview of the Env structure and function with a particular emphasis on the CTT and recent studies that highlight its functionally rich nature. PMID:23079381

  16. Antigenicity and immunogenicity of transmitted/founder, consensus, and chronic envelope glycoproteins of human immunodeficiency virus type 1.

    PubMed

    Liao, Hua-Xin; Tsao, Chun-Yen; Alam, S Munir; Muldoon, Mark; Vandergrift, Nathan; Ma, Ben-Jiang; Lu, Xiaozhi; Sutherland, Laura L; Scearce, Richard M; Bowman, Cindy; Parks, Robert; Chen, Haiyan; Blinn, Julie H; Lapedes, Alan; Watson, Sydeaka; Xia, Shi-Mao; Foulger, Andrew; Hahn, Beatrice H; Shaw, George M; Swanstrom, Ron; Montefiori, David C; Gao, Feng; Haynes, Barton F; Korber, Bette

    2013-04-01

    Human immunodeficiency virus type 1 (HIV-1) vaccine development requires selection of appropriate envelope (Env) immunogens. Twenty HIV-1 Env glycoproteins were examined for their ability to bind human anti-HIV-1 monoclonal antibodies (MAbs) and then used as immunogens in guinea pigs to identify promising immunogens. These included five Envs derived from chronically infected individuals, each representing one of five common clades and eight consensus Envs based on these five clades, as well as the consensus of the entire HIV-1 M group, and seven transmitted/founder (T/F) Envs from clades B and C. Sera from immunized guinea pigs were tested for neutralizing activity using 36 HIV-1 Env-pseudotyped viruses. All Envs bound to CD4 binding site, membrane-proximal, and V1/V2 MAbs with similar apparent affinities, although the T/F Envs bound with higher affinity to the MAb 17b, a CCR5 coreceptor binding site antibody. However, the various Envs differed in their ability to induce neutralizing antibodies. Consensus Envs elicited the most potent responses, but neutralized only a subset of viruses, including mostly easy-to-neutralize tier 1 and some more-difficult-to-neutralize tier 2 viruses. T/F Envs elicited fewer potent neutralizing antibodies but exhibited greater breadth than chronic or consensus Envs. Finally, chronic Envs elicited the lowest level and most limited breadth of neutralizing antibodies overall. Thus, each group of Env immunogens elicited a different antibody response profile. The complementary benefits of consensus and T/F Env immunogens raise the possibility that vaccines utilizing a combination of consensus and T/F Envs may be able to induce neutralizing responses with greater breadth and potency than single Env immunogens. PMID:23365441

  17. Characterization of Antibody Responses Elicited by Human Immunodeficiency Virus Type 1 Primary Isolate Trimeric and Monomeric Envelope Glycoproteins in Selected Adjuvants†

    PubMed Central

    Li, Y.; Svehla, K.; Mathy, N. L.; Voss, G.; Mascola, J. R.; Wyatt, R.

    2006-01-01

    We previously reported that soluble, stable YU2 gp140 trimeric human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein immunogens could elicit improved breadth of neutralization against HIV-1 isolates compared to monomeric YU2 gp120 proteins. In this guinea pig immunization study, we sought to extend these data and determine if adjuvant could quantitatively or qualitatively alter the neutralizing response elicited by trimeric or monomeric immunogens. Consistent with our earlier studies, the YU2 gp140 immunogens elicited higher-titer neutralizing antibodies against homologous and heterologous isolates than those elicited by monomeric YU2 gp120. Additionally, the GlaxoSmithKline family of adjuvants AS01B, AS02A, and AS03 induced higher levels of neutralizing antibodies compared to emulsification of the same immunogens in Ribi adjuvant. Further analysis of vaccine sera indicated that homologous virus neutralization was not mediated by antibodies to the V3 loop, although V3 loop-directed neutralization could be detected for some heterologous isolates. In most gp120-inoculated animals, the homologous YU2 neutralization activity was inhibited by a peptide derived from the YU2 V1 loop, whereas the neutralizing activity elicited by YU2 gp140 trimers was much less sensitive to V1 peptide inhibition. Consistent with a less V1-focused antibody response, sera from the gp140-immunized animals more efficiently neutralized heterologous HIV-1 isolates, as determined by two distinct neutralization formats. Thus, there appear to be qualitative differences in the neutralizing antibody response elicited by YU2 gp140 compared to YU2 monomeric gp120. Further mapping analysis of more conserved regions of gp120/gp41 may be required to determine the neutralizing specificity elicited by the trimeric immunogens. PMID:16415019

  18. Sensory neuropathy in human immunodeficiency virus\\/acquired immunodeficiency syndrome patients: Protease inhibitorâ??mediated neurotoxicity

    Microsoft Academic Search

    Jacqueline A. Pettersen; Gareth Jones; Catherine Worthington; Hartmut B. Krentz; Oliver T. Keppler; Ahmet Hoke; M. John Gill; Christopher Power

    2006-01-01

    Objective: Human immunodeficiency virus-associated sensory neuropathy (HIV-SN) is a common and disabling disorder, often associated with antiretroviral therapy (ART) use. We investigated the clinical features and associated pathogenic determinants of HIV-SN in a neurological cohort of HIV-infected patients, together with a novel model of HIV-SN. Methods: HIV-infected patients with neurological disease were investigated in terms of clinical and laboratory aspects

  19. Observations After Human Immunodeficiency Virus Immunization and Challenge of Human Immunodeficiency Virus Seropositive and Seronegative Chimpanzees

    Microsoft Academic Search

    Clarence J. Gibbs Jr.; Robert Peters; Maneth Gravell; Bruce K. Johnson; Fred C. Jensen; Dennis J. Carlo; Jonas Salk

    1991-01-01

    Two human immunodeficiency virus (HIV)-seropositive chimpanzees (A-3 and A-86c) infected 4 yr earlier with HIV, along with one uninfected animal (A-36), were inoculated intramuscularly three times in a year with a gamma-irradiated gp120-depleted HIV immunogen in incomplete Freund's adjuvant. Both previously infected animals promptly developed an anamnestic humoral antibody response after the first dose, and the uninfected animal developed a

  20. Neutral beam development plan

    SciTech Connect

    Staten, H S [comp.] [comp.

    1980-08-01

    The national plan is presented for developing advanced injection systems for use on upgrades of existing experiments, and use on future facilities such as ETF, to be built in the late 1980's or early 90's where power production from magnetic fusion will move closer to a reality. Not only must higher power and longer pulse length systems be developed , but they must operate reliably; they must be a tool for the experimenter, not the experiment itself. Neutral beam systems handle large amounts of energy and as such, they often are as complicated as the plasma physics experiment itself. This presents a significant challenge to the neutral beam developer.

  1. A comparison of in vitro, immuno-suppressive and clinical effects of goat and horse anti-human thymocyte globulin in macaca monkeys

    PubMed Central

    Kelly, G. E.; Sheil, A. G. R.; Mears, D. C.

    1973-01-01

    Anti-human thymocyte globulin was raised in four goats and two horses. The in vitro properties were defined, and clinical effects and immunosuppressive efficacy were tested in Macaca monkeys bearing skin xenografts or allografts. All goat and one horse ALG preparation produced significant graft prolongation; one horse ALG showed no in vivo immune suppression. Graft survival correlated well with the rosette-inhibiting activities of the various ALG batches. Goat ALG was well tolerated and produced no local, systemic or anaphylactic reactions; both horse ALG preparations consistently produced local reactions, serum sickness, and, occasionally severe anaphylactic reactions in sensitized and non-sensitized monkeys. Prolonged treatment with goat or horse ALG for up to 10 months caused lymphocyte depletion and plasmacytosis in lymph nodes and spleen but no other apparent pathological changes in a wide variety of tissues studied; infective complications did not occur. Goat IgG was more immunogenic than horse but circulating antibody titres to xenogenic IgG could not be related to clinical responses to ALG, to deposition of xenogenic IgG in kidneys, or to immunosuppressive potency of ALG batches. It was concluded that goat ALG was consistently more potent and less toxic than horse ALG. PMID:4197827

  2. Evolution of nef variants in gut associated lymphoid tissue of rhesus macaques during primary simian immunodeficiency virus infection

    SciTech Connect

    Ndolo, Thomas [Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA 95616 (United States); Syvanen, Michael [Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA 95616 (United States); Ellison, Thomas [Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA 95616 (United States); Dandekar, Satya [Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA 95616 (United States)]. E-mail: sdandekar@ucdavis.edu

    2005-12-05

    We utilized the simian immunodeficiency virus model of AIDS to examine evolution of nef gene in gut-associated lymphoid tissue (GALT) during primary and early asymptomatic stages of infection. Macaques were infected with a cloned virus, SIVmac239/nef-stop harboring a premature stop codon in the nef gene. Restoration of the nef open reading frame occurred in GALT early at 3 days post-infection. Analysis of nef sequences by phylogenetic tools showed that evolution of nef was neutral thereafter, as evidenced by the ratio of synonymous to nonsynonymous substitutions, a star pattern in unrooted trees and distribution of amino acid replacements fitting a simple Poisson process. Two regions encoding for a nuclear localization signal and a CTL epitope were conserved. Thus, GALT was a site for strong positive selection of functional nef during initial stages of infection. However, evolution of the nef gene thereafter was neutral during early asymptomatic stage of infection.

  3. Fatal progressive vaccinia in two immunodeficient infants.

    PubMed

    Olding-Stenkvist, E; Nordbring, F; Larsson, E; Lindblom, B; Wigzell, H

    1980-01-01

    Fatal progressive vaccinia developed in two infants, a girl and a boy, vaccinated at the age of 2 months. Immunodeficiencies comprised both humoral and cell-mediated immunity. In the girl low levels of immunoglobulins and a defect function of lymphocytes was demonstrated. The boy had hypogammaglobulinemia and lack of T-lymphocytes. There was a marked hypoplasia of thymus and lymphoid organs in both infants. Both infants had the haplotype A3, B8 and in the boy a crossing over had taken place within the HLA region. No effect was achieved with antivaccinia immunoglobulin and concomitant antiviral therapy (thiosemicarbazone, adenine arabinoside). Interferon therapy gave no clinical improvement, nor did transfer factor. PMID:6937980

  4. The acquired immunodeficiency syndrome in gay men.

    PubMed

    Jaffe, H W; Hardy, A M; Morgan, W M; Darrow, W W

    1985-11-01

    The acquired immunodeficiency syndrome (AIDS) is a major health problem for gay men in the United States. About three fourths of all reported cases have occurred in this population, and the number is projected to double in the next year. In Manhattan and San Francisco, AIDS is now the leading cause of premature mortality in men aged 25 to 44 years who have never married. In a sample of a cohort of gay men enrolled in a San Francisco clinic, 2.7% of the men had the syndrome and 26% had related conditions in 1984. Antibody to human T-lymphotropic virus, type III/lymphadenopathy-associated virus was found in sera from 67% of the men, including 58% of asymptomatic men. Behavioral factors associated with an increased risk of AIDS include large numbers of sexual partners, receptive anal intercourse, and "fisting." The adoption of safer lifestyles is currently the basis of attempts to control the syndrome in gay men. PMID:2996396

  5. Four families with immunodeficiency and chromosome abnormalities.

    PubMed Central

    Candy, D C; Hayward, A R; Hughes, D T; Layward, L; Soothill, J F

    1979-01-01

    Six children, with severe deficiency of some or all of the immunoglobulins and minor somatic abnormalities, had chromosomal abnormalities: (1) 45,XY,t(13q/18q), (2) 46,XY,21ps +, (3) two brothers 46,XY (inv. 7) (4) 45,X,t(11p/10p)/46X,iXq,t(11p/10p) and, (5) in addendum, 45,XX,-18;46,XX, r18. The chromosome abnormalities were detected in B- as well as T-lymphocytes (as evidenced by using both PHA- and PWM-stimulated cultures) in all probands, but one was mosaic in PHA culture, although all his PWM-stimulated cells were abnormal. Chromosomal variants were also detected in relatives of three and immunodeficiency in relatives of two. Images Fig. 1 Fig. 3 PMID:314782

  6. GRANULOMATOUS DISEASE in COMMON VARIABLE IMMUNODEFICIENCY#

    PubMed Central

    Ardeniz, Ömür; Cunningham-Rundles, Charlotte

    2009-01-01

    Granulomatous disease occurs in 8-22% of patients with common variable immunodeficiency (CVID). We examined the clinical and immunologic information of all 37 of 455 (8.1%) CVID subjects with this complication. The median age at diagnosis of CVID was 26 (2 - 59). 14 had granulomas 1 - 18 years before diagnosis of CVID. In 6 detection of granulomas coincided with this diagnosis; for 17, granulomas were documented later. 54% had lung granulomas, 43% in lymph nodes and 32% in liver. 54% of the group had had autoimmune diseases, mostly immune thrombocytopenia and hemolytic anemia. 24% had had a splenectomy. Nineteen (51.3%) required steroid treatment for granulomas; other immune suppressants were used in some. Over 25 years 28.5% died (median age 37.5), but not significantly more when compared to our CVID patients without granulomas (19.8%). Those with lung granulomas had similar mortality to those with granulomas in other tissues. PMID:19716342

  7. Bleach Neutralizes Mold Allergens

    ERIC Educational Resources Information Center

    Science Teacher, 2005

    2005-01-01

    Researchers at National Jewish Medical and Research Center have demonstrated that dilute bleach not only kills common household mold, but may also neutralize the mold allergens that cause most mold-related health complaints. The study, published in the Journal of Allergy and Clinical Immunology, is the first to test the effect on allergic…

  8. RE: pedagogy – after neutrality

    Microsoft Academic Search

    John IAnson

    2010-01-01

    Within the UK and in many parts of the world, official accounts of what it is to make sense of religion are framed within a rhetorics of neutrality in which such study is premised upon the possibility of dispassionate engagement and analysis. This paper, which is largely theoretical in scope, explores both the affordances and the costs of such an

  9. Neutral polar wind

    Microsoft Academic Search

    Larry C. Gardner; Robert W. Schunk

    2004-01-01

    The classical polar wind is an ambipolar outflow of ions from high latitudes along open geomagnetic field lines. The polar wind consists of light thermal ions (H+, He+) and energetic light and heavy ions (H+, He+, O+). The characteristics of these ions have been studied quite extensively since the 1960s. In just the last 20 years, however, energetic neutral atoms

  10. Haematological abnormalities in human immunodeficiency virus (HIV) disease.

    PubMed Central

    Costello, C

    1988-01-01

    Peripheral blood and bone marrow changes are commonly seen in disease associated with human immunodeficiency virus (HIV). This annotation aims to summarise these changes and to suggest possible factors entailed in their occurrence. PMID:3045157

  11. Transfer of neuropathogenic simian immunodeficiency virus with naturally infected microglia.

    PubMed Central

    Watry, D.; Lane, T. E.; Streb, M.; Fox, H. S.

    1995-01-01

    The central nervous system (CNS) is a target for human immunodeficiency virus infection, and, in individuals with acquired immune deficiency syndrome, this can lead to a devastating dementia. Only certain viral variants appear capable of invading the CNS and infecting microglia and brain macrophages. To determine whether the virus entering the brain may be particularly pathogenic to the CNS, we isolated microglia from the brains of simian immunodeficiency virus-infected rhesus monkeys. Serial transfer of these cells into naive animals indicated that productive simian immunodeficiency virus infection could indeed be transferred. Furthermore, CNS infection occurred within a relatively short time span and was associated with viral gene expression in the brain and pathology characteristic of human immunodeficiency virus encephalitis. While demonstrating that neuropathogenic variants partition into the CNS, our approach will allow the dissection of functional neuropathogenic elements present in these viruses. Images Figure 2 Figure 4 Figure 5 Figure 6 Figure 7 PMID:7717458

  12. Building networks for immunodeficiency diseases and immunology training.

    PubMed

    Burrows, Peter D; Fischer, Alain

    2008-09-01

    The RIKEN Research Center for Allergy and Immunology in Japan is reaching out regionally to the primary immunodeficiency disease community and internationally to graduate students and postdoctoral fellows. PMID:18711439

  13. Anhidrotic ectodermal dysplasia and immunodeficiency: the role of NEMO.

    PubMed

    Carrol, E D; Gennery, A R; Flood, T J; Spickett, G P; Abinun, M

    2003-04-01

    Anhidrotic (hypohidrotic) ectodermal dysplasia associated with immunodeficiency (EDA-ID; OMIM 300291) is a newly recognised primary immunodeficiency caused by mutations in NEMO, the gene encoding nuclear factor kappaB (NF-kappaB) essential modulator, NEMO, or inhibitor of kappaB kinase (IKK-gamma). This protein is essential for activation of the transcription factor NF-kappaB, which plays an important role in human development, skin homoeostasis, and immunity. PMID:12651765

  14. Neutral particle beam intensity controller

    DOEpatents

    Dagenhart, William K. (Oak Ridge, TN)

    1986-01-01

    A neutral beam intensity controller is provided for a neutral beam generator in which a neutral beam is established by accelerating ions from an ion source into a gas neutralizer. An amplitude modulated, rotating magnetic field is applied to the accelerated ion beam in the gas neutralizer to defocus the resultant neutral beam in a controlled manner to achieve intensity control of the neutral beam along the beam axis at constant beam energy. The rotating magnetic field alters the orbits of ions in the gas neutralizer before they are neutralized, thereby controlling the fraction of neutral particles transmitted out of the neutralizer along the central beam axis to a fusion device or the like. The altered path or defocused neutral particles are sprayed onto an actively cooled beam dump disposed perpendicular to the neutral beam axis and having a central open for passage of the focused beam at the central axis of the beamline. Virtually zero therough 100% intensity control is achieved by varying the magnetic field strength without altering the ion source beam intensity or its species yield.

  15. Envelope Variants Circulating as Initial Neutralization Breadth Developed in Two HIV-Infected Subjects Stimulate Multiclade Neutralizing Antibodies in Rabbits

    PubMed Central

    Malherbe, Delphine C.; Pissani, Franco; Sather, D. Noah; Guo, Biwei; Pandey, Shilpi; Sutton, William F.; Stuart, Andrew B.; Robins, Harlan; Park, Byung; Krebs, Shelly J.; Schuman, Jason T.; Kalams, Spyros; Hessell, Ann J.

    2014-01-01

    ABSTRACT Identifying characteristics of the human immunodeficiency virus type 1 (HIV-1) envelope that are effective in generating broad, protective antibodies remains a hurdle to HIV vaccine design. Emerging evidence of the development of broad and potent neutralizing antibodies in HIV-infected subjects suggests that founder and subsequent progeny viruses may express unique antigenic motifs that contribute to this developmental pathway. We hypothesize that over the course of natural infection, B cells are programmed to develop broad antibodies by exposure to select populations of emerging envelope quasispecies variants. To test this hypothesis, we identified two unrelated subjects whose antibodies demonstrated increasing neutralization breadth against a panel of HIV-1 isolates over time. Full-length functional env genes were cloned longitudinally from these subjects from months after infection through 2.6 to 5.8 years of infection. Motifs associated with the development of breadth in published, cross-sectional studies were found in both subjects. We compared the immunogenicity of envelope vaccines derived from time points obtained during and after broadening of neutralization activity within these subjects. Rabbits were coimmunized four times with selected multiple gp160 DNAs and gp140-trimeric envelope proteins. The affinity of the polyclonal response increased as a function of boosting. The most rapid and persistent neutralization of multiclade tier 1 viruses was elicited by envelopes that were circulating in plasma at time points prior to the development of 50% neutralization breadth in both human subjects. The breadth elicited in rabbits was not improved by exposure to later envelope variants. These data have implications for vaccine development in describing a target time point to identify optimal envelope immunogens. IMPORTANCE Vaccine protection against viral infections correlates with the presence of neutralizing antibodies; thus, vaccine components capable of generating potent neutralization are likely to be critical constituents in an effective HIV vaccine. However, vaccines tested thus far have elicited only weak antibody responses and very modest, waning protection. We hypothesized that B cells develop broad antibodies by exposure to the evolving viral envelope population and tested this concept using multiple envelopes from two subjects who developed neutralization breadth within a few years of infection. We compared different combinations of envelopes from each subject to identify the most effective immunogens and regimens. In each subject, use of HIV envelopes circulating during the early development and maturation of breadth generated more-potent antibodies that were modestly cross neutralizing. These data suggest a new approach to identifying envelope immunogens that may be more effective in generating protective antibodies in humans. PMID:25210191

  16. Neutral particle beam intensity controller

    DOEpatents

    Dagenhart, W.K.

    1984-05-29

    The neutral beam intensity controller is based on selected magnetic defocusing of the ion beam prior to neutralization. The defocused portion of the beam is dumped onto a beam dump disposed perpendicular to the beam axis. Selective defocusing is accomplished by means of a magnetic field generator disposed about the neutralizer so that the field is transverse to the beam axis. The magnetic field intensity is varied to provide the selected partial beam defocusing of the ions prior to neutralization. The desired focused neutral beam portion passes along the beam path through a defining aperture in the beam dump, thereby controlling the desired fraction of neutral particles transmitted to a utilization device without altering the kinetic energy level of the desired neutral particle fraction. By proper selection of the magnetic field intensity, virtually zero through 100% intensity control of the neutral beam is achieved.

  17. Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01

    SciTech Connect

    Zhou, Tongqing; Georgiev, Ivelin; Wu, Xueling; Yang, Zhi-Yong; Dai, Kaifan; Finzi, Andrés; Kwon, Young Do; Scheid, Johannes F.; Shi, Wei; Xu, Ling; Yang, Yongping; Zhu, Jiang; Nussenzweig, Michel C.; Sodroski, Joseph; Shapiro, Lawrence; Nabel, Gary J.; Mascola, John R.; Kwong, Peter D. (NIH); (Rockefeller); (DFCI)

    2010-08-26

    During HIV-1 infection, antibodies are generated against the region of the viral gp120 envelope glycoprotein that binds CD4, the primary receptor for HIV-1. Among these antibodies, VRC01 achieves broad neutralization of diverse viral strains. We determined the crystal structure of VRC01 in complex with a human immunodeficiency virus HIV-1 gp120 core. VRC01 partially mimics CD4 interaction with gp120. A shift from the CD4-defined orientation, however, focuses VRC01 onto the vulnerable site of initial CD4 attachment, allowing it to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. To achieve this recognition, VRC01 contacts gp120 mainly through immunoglobulin V-gene regions substantially altered from their genomic precursors. Partial receptor mimicry and extensive affinity maturation thus facilitate neutralization of HIV-1 by natural human antibodies.

  18. Cell-specific temporal infection of the brain in a simian immunodeficiency virus model of human immunodeficiency virus encephalitis

    Microsoft Academic Search

    Katherine A. Thompson; John J. Varrone; Tanja Jankovic-Karasoulos; Steven L. Wesselingh; Catriona A. McLean

    2009-01-01

    Increasing evidence supports early brain infection by human immunodeficiency virus (HIV). Definitive temporal studies determining\\u000a when and within which brain cells viral DNA is present are lacking. This study utilized simian immunodeficiency virus (SIV)-infected\\u000a macaques sacrificed at days 10, 21, 56, and 84 post inoculation. Laser-microdissection isolated pure perivascular macrophage,\\u000a parenchymal microglia, and astrocyte populations. Nested polymerase chain reaction (PCR)

  19. Neutral atom traps.

    SciTech Connect

    Pack, Michael Vern

    2008-12-01

    This report describes progress in designing a neutral atom trap capable of trapping sub millikelvin atom in a magnetic trap and shuttling the atoms across the atom chip from a collection area to an optical cavity. The numerical simulation and atom chip design are discussed. Also, discussed are preliminary calculations of quantum noise sources in Kerr nonlinear optics measurements based on electromagnetically induced transparency. These types of measurements may be important for quantum nondemolition measurements at the few photon limit.

  20. Antihypertensive neutral lipid

    DOEpatents

    Snyder, F.L.; Blank, M.L.

    1984-10-26

    The invention relates to the discovery of a class of neutral acetylated either-linked glycerolipids having the capacity to lower blood presure in warm-blooded animals. This physiological effect is structure sensitive requiring a long chain alkyl group at the sn-1 position and a short carbon chain acyl group (acetyl or propionyl) at the sn-2 position, and a hydroxyl group at the sn-3 position.

  1. Neutrality between Government and Religion.

    ERIC Educational Resources Information Center

    Mawdsley, Ralph D.

    1996-01-01

    The overall guiding principle of neutrality between government and religion masks a tension that exists between free exercise of religion and establishment of religion. Reviews the development and current status of "Lemon" as a test for neutrality; proposes a new test for neutrality, evenhandedness, that is common to both the Free Exercise and…

  2. Electrostatic potential of human immunodeficiency virus type 2 and rhesus macaque simian immunodeficiency virus capsid proteins.

    PubMed

    Bozek, Katarzyna; Nakayama, Emi E; Kono, Ken; Shioda, Tatsuo

    2012-01-01

    Human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency virus isolated from a macaque monkey (SIVmac) are assumed to have originated from simian immunodeficiency virus isolated from sooty mangabey (SIVsm). Despite their close similarity in genome structure, HIV-2 and SIVmac show different sensitivities to TRIM5?, a host restriction factor against retroviruses. The replication of HIV-2 strains is potently restricted by rhesus (Rh) monkey TRIM5?, while that of SIVmac strain 239 (SIVmac239) is not. Viral capsid protein is the determinant of this differential sensitivity to TRIM5?, as the HIV-2 mutant carrying SIVmac239 capsid protein evaded Rh TRIM5?-mediated restriction. However, the molecular determinants of this restriction mechanism are unknown. Electrostatic potential on the protein-binding site is one of the properties regulating protein-protein interactions. In this study, we investigated the electrostatic potential on the interaction surface of capsid protein of HIV-2 strain GH123 and SIVmac239. Although HIV-2 GH123 and SIVmac239 capsid proteins share more than 87% amino acid identity, we observed a large difference between the two molecules with the HIV-2 GH123 molecule having predominantly positive and SIVmac239 predominantly negative electrostatic potential on the surface of the loop between ?-helices 4 and 5 (L4/5). As L4/5 is one of the major determinants of Rh TRIM5? sensitivity of these viruses, the present results suggest that the binding site of the Rh TRIM5? may show complementarity to the HIV-2 GH123 capsid surface charge distribution. PMID:22679444

  3. Electrostatic Potential of Human Immunodeficiency Virus Type 2 and Rhesus Macaque Simian Immunodeficiency Virus Capsid Proteins

    PubMed Central

    Bozek, Katarzyna; Nakayama, Emi E.; Kono, Ken; Shioda, Tatsuo

    2012-01-01

    Human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency virus isolated from a macaque monkey (SIVmac) are assumed to have originated from simian immunodeficiency virus isolated from sooty mangabey (SIVsm). Despite their close similarity in genome structure, HIV-2 and SIVmac show different sensitivities to TRIM5?, a host restriction factor against retroviruses. The replication of HIV-2 strains is potently restricted by rhesus (Rh) monkey TRIM5?, while that of SIVmac strain 239 (SIVmac239) is not. Viral capsid protein is the determinant of this differential sensitivity to TRIM5?, as the HIV-2 mutant carrying SIVmac239 capsid protein evaded Rh TRIM5?-mediated restriction. However, the molecular determinants of this restriction mechanism are unknown. Electrostatic potential on the protein-binding site is one of the properties regulating protein–protein interactions. In this study, we investigated the electrostatic potential on the interaction surface of capsid protein of HIV-2 strain GH123 and SIVmac239. Although HIV-2 GH123 and SIVmac239 capsid proteins share more than 87% amino acid identity, we observed a large difference between the two molecules with the HIV-2 GH123 molecule having predominantly positive and SIVmac239 predominantly negative electrostatic potential on the surface of the loop between ?-helices 4 and 5 (L4/5). As L4/5 is one of the major determinants of Rh TRIM5? sensitivity of these viruses, the present results suggest that the binding site of the Rh TRIM5? may show complementarity to the HIV-2 GH123 capsid surface charge distribution. PMID:22679444

  4. Role of a Putative gp41 Dimerization Domain in Human Immunodeficiency Virus Type 1 Membrane Fusion

    SciTech Connect

    Liu, J.; Deng, Y; Li, Q; Dey, A; Moore, J; Lu, M

    2010-01-01

    The entry of human immunodeficiency virus type 1 (HIV-1) into a target cell entails a series of conformational changes in the gp41 transmembrane glycoprotein that mediates the fusion of the viral and target cell membranes. A trimer-of-hairpins structure formed by the association of two heptad repeat (HR) regions of the gp41 ectodomain has been implicated in a late step of the fusion pathway. Earlier native and intermediate states of the protein are postulated to mediate the antiviral activity of the fusion inhibitor enfuvirtide and of broadly neutralizing monoclonal antibodies (NAbs), but the details of these structures remain unknown. Here, we report the identification and crystal structure of a dimerization domain in the C-terminal ectodomain of gp41 (residues 630 to 683, or C54). Two C54 monomers associate to form an asymmetric, antiparallel coiled coil with two distinct C-terminal {alpha}-helical overhangs. This dimer structure is conferred largely by interactions within a central core that corresponds to the sequence of enfuvirtide. The mutagenic alteration of the dimer interface severely impairs the infectivity of Env-pseudotyped viruses. Moreover, the C54 structure binds tightly to both the 2F5 and 4E10 NAbs and likely represents a potential intermediate conformation of gp41. These results should enhance our understanding of the molecular basis of the gp41 fusogenic structural transitions and thereby guide rational, structure-based efforts to design new fusion inhibitors and vaccine candidates intended to induce broadly neutralizing antibodies.

  5. A Stiffness Switch in Human Immunodeficiency Virus

    PubMed Central

    Kol, Nitzan; Shi, Yu; Tsvitov, Marianna; Barlam, David; Shneck, Roni Z.; Kay, Michael S.; Rousso, Itay

    2007-01-01

    After budding from the cell, human immunodeficiency virus (HIV) and other retrovirus particles undergo a maturation process that is required for their infectivity. During maturation, HIV particles undergo a significant internal morphological reorganization, changing from a roughly spherically symmetric immature particle with a thick protein shell to a mature particle with a thin protein shell and conical core. However, the physical principles underlying viral particle production, maturation, and entry into cells remain poorly understood. Here, using nanoindentation experiments conducted by an atomic force microscope (AFM), we report the mechanical measurements of HIV particles. We find that immature particles are more than 14-fold stiffer than mature particles and that this large difference is primarily mediated by the HIV envelope cytoplasmic tail domain. Finite element simulation shows that for immature virions the average Young's modulus drops more than eightfold when the cytoplasmic tail domain is deleted (930 vs. 115 MPa). We also find a striking correlation between the softening of viruses during maturation and their ability to enter cells, providing the first evidence, to our knowledge, for a prominent role for virus mechanical properties in the infection process. These results show that HIV regulates its mechanical properties at different stages of its life cycle (i.e., stiff during viral budding versus soft during entry) and that this regulation may be important for efficient infectivity. Our report of this maturation-induced “stiffness switch” in HIV establishes the groundwork for mechanistic studies of how retroviral particles can regulate their mechanical properties to affect biological function. PMID:17158573

  6. Infections and immunodeficiency in Down syndrome

    PubMed Central

    Ram, G; Chinen, J

    2011-01-01

    Down syndrome (DS) is the most common genetic disease and presents with cognitive impairment, cardiac and gastrointestinal abnormalities, in addition to other miscellaneous clinical conditions. DS individuals may have a high frequency of infections, usually of the upper respiratory tract, characterized by increased severity and prolonged course of disease, which are partially attributed to defects of the immune system. The abnormalities of the immune system associated with DS include: mild to moderate T and B cell lymphopenia, with marked decrease of naive lymphocytes, impaired mitogen-induced T cell proliferation, reduced specific antibody responses to immunizations and defects of neutrophil chemotaxis. Limited evidence of genetic abnormalities secondary to trisomy of chromosome 21 and affecting the immune system is available, such as the potential consequences of gene over-expression, most significantly SOD1 and RCAN1. Secondary immunodeficiency due to metabolic or nutritional factors in DS, particularly zinc deficiency, has been postulated. Non-immunological factors, including abnormal anatomical structures (e.g. small ear canal, tracheomalacia) and gastro-oesophageal reflux, may play a role in the increased frequency of respiratory tract infections. The molecular mechanisms leading to the immune defects observed in DS individuals and the contribution of these immunological abnormalities to the increased risk of infections require further investigation. Addressing immunological and non-immunological factors involved in the pathogenesis of infectious diseases may reduce the susceptibility to infections in DS subjects. PMID:21352207

  7. Immunodeficiency and laser magnetic therapy in urology

    NASA Astrophysics Data System (ADS)

    Maati, Moufagued; Rozanov, Vladimir V.; Avdoshin, V. P.

    1996-11-01

    The importance of immunodeficiency problem has increased last time not only due to AIDS appearance, but also to a great extent as a result of the development and active practical use of the methods of immunology parameters investigations. Al great pharmaceutical firms are organizing the process of creating the drugs, influencing on the different phases of immunity, but unfortunately, the problem of their adverse effect and connected complications is till today a milestone. A great number of investigations, proving a good effect of laser-magnetic therapy concerning immune system have been done today. There is, in particular, changing of blood counts and immunologic tests after intravenous laser irradiation of blood. Intravenous laser irradiation of blood results in increasing of lymphocytes, T-immuno stimulation, stabilization of t-lymphocyte subpopulation, increasing of t-lymphocyte helper activity and decreasing of suppressor one.Under this laser action number of circulating immune complexes is decreased, and blood serum bactericide activity and lisozyme number are increased.

  8. Infections and immunodeficiency in Down syndrome.

    PubMed

    Ram, G; Chinen, J

    2011-04-01

    Down syndrome (DS) is the most common genetic disease and presents with cognitive impairment, cardiac and gastrointestinal abnormalities, in addition to other miscellaneous clinical conditions. DS individuals may have a high frequency of infections, usually of the upper respiratory tract, characterized by increased severity and prolonged course of disease, which are partially attributed to defects of the immune system. The abnormalities of the immune system associated with DS include: mild to moderate T and B cell lymphopenia, with marked decrease of naive lymphocytes, impaired mitogen-induced T cell proliferation, reduced specific antibody responses to immunizations and defects of neutrophil chemotaxis. Limited evidence of genetic abnormalities secondary to trisomy of chromosome 21 and affecting the immune system is available, such as the potential consequences of gene over-expression, most significantly SOD1 and RCAN1. Secondary immunodeficiency due to metabolic or nutritional factors in DS, particularly zinc deficiency, has been postulated. Non-immunological factors, including abnormal anatomical structures (e.g. small ear canal, tracheomalacia) and gastro-oesophageal reflux, may play a role in the increased frequency of respiratory tract infections. The molecular mechanisms leading to the immune defects observed in DS individuals and the contribution of these immunological abnormalities to the increased risk of infections require further investigation. Addressing immunological and non-immunological factors involved in the pathogenesis of infectious diseases may reduce the susceptibility to infections in DS subjects. PMID:21352207

  9. [Acute myelocytic leukemia in immunodeficiency virus infection].

    PubMed

    Pulik, M; Lionnet, F; Genet, P; Jary, L; Jondeau, K

    1998-12-01

    B lineage-derived malignant proliferation is a well recognized complication of HIV infection. Acute myeloid leukemias have been reported but no complete review of these cases has been performed. The Medline database was reviewed for the years 1980-1997. Eighteen cases of AML have been reported. When previously known, HIV infection was present for 40 months. In 7 patients HIV infection and AML were diagnosed simultaneously. According to the FAB classification, 5 cases were M2, 8 M4, 5 M5. Extramedullary localizations (skin, testis, spleen) were noticed in 10 patients. Non-treated patients had a survival of 2.7 weeks versus 9.8 months in patients treated with chemotherapy. Pathophysiologic studies were performed in 3 cases: reverse transcriptase activity and p24 antigen were noted in tumoral cultured cells in 1 case; absence of viral particules in culture in another one; absence of cloned DNA provirus integration in blasts cells in a third patient. Based on the observed high rate of M4/M5 (72%) versus 19-36% expected in a non HIV-infected population, we postulate that the association of AML and HIV is not coincidental. The monocytotropism of HIV, the chronic cytokines-mediated activation of monocyte/macrophages, the immunodeficiency may explain this association. PMID:10021898

  10. Neutral beam injection system

    SciTech Connect

    Duesing, G.; Altmann, H.; Falter, H.; Goede, A.; Haange, R.; Hemsworth, R.S.; Kupschus, P.; Stork, D.; Thompson, E.

    1987-01-01

    The development of the neutral injection (NI) system for the Joint European Torus and its status in 1985 are reported. First the system parameters are discussed and the layout is described, followed by a summary of the physics design calculations, the development, production, and testing of the components and the subsystem assembly. The system commissioning is presented, including a description of the function and the realization of the NI test bed. A summary of performance predictions for 80-keV beam heating experiments, and of the experimental evidence on balanced versus coinjection, is presented. The operational experience with the first injector and the plasma physics results obtained so far are summarized.

  11. Binding of the 2F5 Monoclonal Antibody to Native and Fusion-Intermediate Forms of Human Immunodeficiency Virus Type 1 gp41: Implications for Fusion-Inducing Conformational Changes

    PubMed Central

    de Rosny, Eve; Vassell, Russell; Jiang, Shibo; Kunert, Renate; Weiss, Carol D.

    2004-01-01

    We investigated how the broadly neutralizing monoclonal antibody 2F5 affects the human immunodeficiency virus type 1 envelope glycoprotein as it undergoes receptor-induced conformational changes and show that 2F5 binds both native and fusion-intermediate conformations, suggesting inhibition of a late step in virus entry. We also demonstrate conformational changes in the C heptad of gp41. PMID:14963170

  12. Frequent transmission of immunodeficiency viruses among bobcats and pumas.

    PubMed

    Franklin, S P; Troyer, J L; Terwee, J A; Lyren, L M; Boyce, W M; Riley, S P D; Roelke, M E; Crooks, K R; Vandewoude, S

    2007-10-01

    With the exception of human immunodeficiency virus (HIV), which emerged in humans after cross-species transmissions of simian immunodeficiency viruses from nonhuman primates, immunodeficiency viruses of the family Lentiviridae represent species-specific viruses that rarely cross species barriers to infect new hosts. Among the Felidae, numerous immunodeficiency-like lentiviruses have been documented, but only a few cross-species transmissions have been recorded, and these have not been perpetuated in the recipient species. Lentivirus seroprevalence was determined for 79 bobcats (Lynx rufus) and 31 pumas (Puma concolor) from well-defined populations in Southern California. Partial genomic sequences were subsequently obtained from 18 and 12 seropositive bobcats and pumas, respectively. Genotypes were analyzed for phylogenic relatedness and genotypic composition among the study set and archived feline lentivirus sequences. This investigation of feline immunodeficiency virus infection in bobcats and pumas of Southern California provides evidence that cross-species infection has occurred frequently among these animals. The data suggest that transmission has occurred in multiple locations and are most consistent with the spread of the virus from bobcats to pumas. Although the ultimate causes remain unknown, these transmission events may occur as a result of puma predation on bobcats, a situation similar to that which fostered transmission of HIV to humans, and likely represent the emergence of a lentivirus with relaxed barriers to cross-species transmission. This unusual observation provides a valuable opportunity to evaluate the ecological, behavioral, and molecular conditions that favor repeated transmissions and persistence of lentivirus between species. PMID:17670835

  13. Intravenous immunoglobulins in immunodeficiencies: more than mere replacement therapy.

    PubMed

    Kaveri, S V; Maddur, M S; Hegde, P; Lacroix-Desmazes, S; Bayry, J

    2011-06-01

    Intravenous immunoglobulin (IVIG) is a therapeutic compound prepared from pools of plasma obtained from several thousand healthy blood donors. For more than 20 years, IVIG has been used in the treatment of a wide range of primary and secondary immunodeficiencies. IVIG now represents a standard therapeutic option for most antibody deficiencies. Routinely, IVIG is used in patients with X-linked agammaglobulinaemia (XLA), common variable immunodeficiency (CVID), X-linked hyper-IgM, severe combined immunodeficiency, Wiskott-Aldrich syndrome, and selective IgG class deficiency. In addition, IVIG is used extensively in the treatment of a wide variety of autoimmune disorders. IVIG is administered at distinct doses in the two clinical settings: whereas immunodeficient patients are treated with replacement levels of IVIG, patients with autoimmune and inflammatory diseases are administered with very high doses of IVIG. Several lines of experimental evidence gathered in the recent years suggest that the therapeutic beneficial effect of IVIG in immunodeficiencies reflects an active role for IVIG, rather than a mere passive transfer of antibodies. PMID:21466545

  14. Intravenous immunoglobulins in immunodeficiencies: more than mere replacement therapy

    PubMed Central

    Kaveri, S V; Maddur, M S; Hegde, P; Lacroix-Desmazes, S; Bayry, J

    2011-01-01

    Intravenous immunoglobulin (IVIG) is a therapeutic compound prepared from pools of plasma obtained from several thousand healthy blood donors. For more than 20 years, IVIG has been used in the treatment of a wide range of primary and secondary immunodeficiencies. IVIG now represents a standard therapeutic option for most antibody deficiencies. Routinely, IVIG is used in patients with X-linked agammaglobulinaemia (XLA), common variable immunodeficiency (CVID), X-linked hyper-IgM, severe combined immunodeficiency, Wiskott-Aldrich syndrome, and selective IgG class deficiency. In addition, IVIG is used extensively in the treatment of a wide variety of autoimmune disorders. IVIG is administered at distinct doses in the two clinical settings: whereas immunodeficient patients are treated with replacement levels of IVIG, patients with autoimmune and inflammatory diseases are administered with very high doses of IVIG. Several lines of experimental evidence gathered in the recent years suggest that the therapeutic beneficial effect of IVIG in immunodeficiencies reflects an active role for IVIG, rather than a mere passive transfer of antibodies. PMID:21466545

  15. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus.

    PubMed

    Liao, Hua-Xin; Lynch, Rebecca; Zhou, Tongqing; Gao, Feng; Alam, S Munir; Boyd, Scott D; Fire, Andrew Z; Roskin, Krishna M; Schramm, Chaim A; Zhang, Zhenhai; Zhu, Jiang; Shapiro, Lawrence; Mullikin, James C; Gnanakaran, S; Hraber, Peter; Wiehe, Kevin; Kelsoe, Garnett; Yang, Guang; Xia, Shi-Mao; Montefiori, David C; Parks, Robert; Lloyd, Krissey E; Scearce, Richard M; Soderberg, Kelly A; Cohen, Myron; Kamanga, Gift; Louder, Mark K; Tran, Lillian M; Chen, Yue; Cai, Fangping; Chen, Sheri; Moquin, Stephanie; Du, Xiulian; Joyce, M Gordon; Srivatsan, Sanjay; Zhang, Baoshan; Zheng, Anqi; Shaw, George M; Hahn, Beatrice H; Kepler, Thomas B; Korber, Bette T M; Kwong, Peter D; Mascola, John R; Haynes, Barton F

    2013-04-25

    Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details of their generation could provide a blueprint for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from the time of infection. The mature antibody, CH103, neutralized approximately 55% of HIV-1 isolates, and its co-crystal structure with the HIV-1 envelope protein gp120 revealed a new loop-based mechanism of CD4-binding-site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the unmutated common ancestor of the CH103 lineage avidly bound the transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody neutralization breadth was preceded by extensive viral diversification in and near the CH103 epitope. These data determine the viral and antibody evolution leading to induction of a lineage of HIV-1 broadly neutralizing antibodies, and provide insights into strategies to elicit similar antibodies by vaccination. PMID:23552890

  16. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...2010-04-01 2010-04-01 false In vitro human immunodeficiency virus (HIV) drug...Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug...assay. (a) Identification . The in vitro HIV drug resistance genotype...

  17. Generation, affinity maturation, and characterization of a human anti-human NKG2D monoclonal antibody with dual antagonistic and agonistic activity

    PubMed Central

    Kwong, Ka Yin; Baskar, Sivasubramanian; Zhang, Hua; Mackall, Crystal L.; Rader, Christoph

    2008-01-01

    Summary In humans, NKG2D is an activating receptor on NK cells and a costimulatory receptor on certain T cells and plays a central role in mediating immune responses in autoimmune diseases, infectious diseases, and cancer. Monoclonal antibodies that antagonize or agonize immune responses mediated by human NKG2D are considered to be of broad and potent therapeutic utility. Nonetheless, monoclonal antibodies to NKG2D that are suitable for clinical investigations have not been published yet. Here we describe the generation, affinity maturation, and characterization of a fully human monoclonal antibody to human NKG2D. Using phage display technology based on a newly generated naïve human Fab library in phage display vector pC3C followed by a tandem chain shuffling process designed for minimal deviation from natural human antibody sequences, we selected a human Fab, designated KYK-2.0, with high specificity and affinity to human NKG2D. KYK-2.0 Fab blocked the binding of the natural human NKG2D ligands MICA, MICB, and ULBP2 as potently as a commercially available mouse anti-human NKG2D monoclonal antibody in IgG format. Conversion of KYK-2.0 Fab to IgG1 resulted in subnanomolar avidity for human NKG2D. KYK-2.0 IgG1 was found to selectively recognize defined subpopulations of human lymphocytes known to express NKG2D, i.e. the majority of human CD8+, CD16+, and CD56+ cells as well as a small fraction of human CD4+ cells. In solution, KYK-2.0 IgG1 interfered with the cytolytic activity of ex vivo expanded human NK cells. By contrast, immobilized KYK-2.0 IgG1 was found to strongly induce human NK cell activation. The dual antagonistic and agonistic activity promises a wide range of therapeutic applications for KYK-2.0 IgG1 and its derivatives. PMID:18809410

  18. Absence of cytotoxic antibody to human immunodeficiency virus-infected cells in humans and its induction in animals after infection or immunization with purified envelope glycoprotein gp120

    SciTech Connect

    Nara, P.L.; Robey, W.G.; Gonda, M.A.; Carter, S.G.; Fischinger, P.J.

    1987-06-01

    The presence of antibody-dependent complement-mediated cytotoxicity (ACC) was assessed in humans and chimpanzees, which are capable of infection with human immunodeficiency virus isolate HTLV-IIIb, and examined in the goat after immunization with the major viral glycoprotein (gp120) of HTLV-IIIb. In infected humans no antibody mediating ACC was observed regardless of the status of disease. Even healthy individuals with high-titer, broadly reactive, neutralizing antibodies has no ACC. In contrast, chimpanzees infected with HTLV-IIIb, from whom virus could be isolated, not only had neutralizing antibody but also antibodies broadly reactive in ACC, even against distantly related human immunodeficiency virus isolates, as well as against their own reisolated virus. In the goat, the gp120 of HTLV-IIIb induced a highly type-specific response as measured by both ACC and flow cytofluorometry of live infected H9 cells. Normal human cells were not subject to ACC by animal anti-HTLV-III gp120-specific sera. Induction of ACC and neutralizing antibody were closely correlated in the animal experimental models but not in humans. The presence of ACC in gp120-inoculated goats and HTLV-III-infected chimpanzees represent a qualitative difference that may be important in the quest for the elicitation of a protective immunity in humans.

  19. Bioengineering human microvascular networks in immunodeficient mice.

    PubMed

    Lin, Ruei-Zeng; Melero-Martin, Juan M

    2011-01-01

    The future of tissue engineering and cell-based therapies for tissue regeneration will likely rely on our ability to generate functional vascular networks in vivo. In this regard, the search for experimental models to build blood vessel networks in vivo is of utmost importance. The feasibility of bioengineering microvascular networks in vivo was first shown using human tissue-derived mature endothelial cells (ECs); however, such autologous endothelial cells present problems for wide clinical use, because they are difficult to obtain in sufficient quantities and require harvesting from existing vasculature. These limitations have instigated the search for other sources of ECs. The identification of endothelial colony-forming cells (ECFCs) in blood presented an opportunity to non-invasively obtain ECs (5-7). We and other authors have shown that adult and cord blood-derived ECFCs have the capacity to form functional vascular networks in vivo. Importantly, these studies have also shown that to obtain stable and durable vascular networks, ECFCs require co-implantation with perivascular cells. The assay we describe here illustrates this concept: we show how human cord blood-derived ECFCs can be combined with bone marrow-derived mesenchymal stem cells (MSCs) as a single cell suspension in a collagen/fibronectin/fibrinogen gel to form a functional human vascular network within 7 days after implantation into an immunodeficient mouse. The presence of human ECFC-lined lumens containing host erythrocytes can be seen throughout the implants indicating not only the formation (de novo) of a vascular network, but also the development of functional anastomoses with the host circulatory system. This murine model of bioengineered human vascular network is ideally suited for studies on the cellular and molecular mechanisms of human vascular network formation and for the development of strategies to vascularize engineered tissues. PMID:21775960

  20. Bioengineering Human Microvascular Networks in Immunodeficient Mice

    PubMed Central

    Lin, Ruei-Zeng; Melero-Martin, Juan M.

    2011-01-01

    The future of tissue engineering and cell-based therapies for tissue regeneration will likely rely on our ability to generate functional vascular networks in vivo. In this regard, the search for experimental models to build blood vessel networks in vivo is of utmost importance 1. The feasibility of bioengineering microvascular networks in vivo was first shown using human tissue-derived mature endothelial cells (ECs) 2-4; however, such autologous endothelial cells present problems for wide clinical use, because they are difficult to obtain in sufficient quantities and require harvesting from existing vasculature. These limitations have instigated the search for other sources of ECs. The identification of endothelial colony-forming cells (ECFCs) in blood presented an opportunity to non-invasively obtain ECs 5-7. We and other authors have shown that adult and cord blood-derived ECFCs have the capacity to form functional vascular networks in vivo7-11. Importantly, these studies have also shown that to obtain stable and durable vascular networks, ECFCs require co-implantation with perivascular cells. The assay we describe here illustrates this concept: we show how human cord blood-derived ECFCs can be combined with bone marrow-derived mesenchymal stem cells (MSCs) as a single cell suspension in a collagen/fibronectin/fibrinogen gel to form a functional human vascular network within 7 days after implantation into an immunodeficient mouse. The presence of human ECFC-lined lumens containing host erythrocytes can be seen throughout the implants indicating not only the formation (de novo) of a vascular network, but also the development of functional anastomoses with the host circulatory system. This murine model of bioengineered human vascular network is ideally suited for studies on the cellular and molecular mechanisms of human vascular network formation and for the development of strategies to vascularize engineered tissues. PMID:21775960

  1. Nodular Regenerative Hyperplasia in Common Variable Immunodeficiency

    PubMed Central

    Fuss, Ivan J.; Friend, Julia; Yang, Zhiqong; He, Ping; Hooda, Lubna; Boyer, James; Xi, Liqiang; Raffeld, Mark; Kleiner, David E.; Heller, Theo; Strober, Warren

    2013-01-01

    Purpose Patients with Common Variable Immunodeficiency (CVID) are subject to the development of a liver disease syndrome known as nodular regenerative hyperplasia (NRH). The purpose of this study was to define the characteristics and course of this complication of CVID. Methods CVID patients were evaluated by retrospective and prospective clinical course review. Liver biopsy specimens were evaluated for evidence of NRH and studied via RT-PCR for cytokine analysis. Results NRH in our CVID patient population occurred in approximately 5% of the 261 patients in our total CVID study group, initially presenting in most cases with an elevated alkaline phosphatase level. While in some patients the disease remained static, in a larger proportion a more severe disease developed characterized by portal hypertension, the latter leading to hypersplenism with neutropenia and thrombocytopenia and, in some cases, to ascites. In addition, a substantial proportion of patients either developed or presented initially with an autoimmune hepatitis-like (AIH-like) liver disease that resulted in severe liver dysfunction and, in most cases to death due to infections. The liver histologic findings in these AIH-like patients were characterized by underlying NRH pattern with superimposed interface hepatitis, lymphocytic infiltration and fibrosis. Immunologic studies of biopsies of NRH patients demonstrated the presence of infiltrating T cells producing IFN-?, suggesting that the NRH is due to an autoimmune process. Conclusion Overall, these studies provide evidence that NRH may not be benign but, can be a severe and potentially fatal disease complication of CVID that merits close monitoring and intervention. PMID:23420139

  2. Medical management of human immunodeficiency virus infection.

    PubMed

    Kempen, John H

    2008-01-01

    The human immunodeficiency virus (HIV)/ acquired immune deficiency syndrome (AIDS) pandemic has pervasive effects on culture, economics, policy, and human development. All organs can be affected by complications of HIV/AIDS, including the eye. When sufficient resources are available and widespread antiretroviral resistance does not exist, the four available classes of antiretroviral agents - nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and fusion inhibitors - can be combined to provide highly active antiretroviral therapy (HAART). For many (not all) patients, HAART converts an inexorably fatal disease into a chronic disease with a fairly good prognosis. Use of HAART often induces partial immune recovery, which has predominantly beneficial effects on ocular complications of AIDS. However, HAART-induced immune recovery sometimes results in immune recovery inflammatory syndromes, such as immune recovery uveitis. Use of HAART is the single most useful intervention for most patients with ocular complications of AIDS. However, specific ocular therapy is also critical to avoid blindness in the early months before immune recovery can occur, or if HAART is unavailable. Increasing availability of HAART worldwide shows great promise to alleviate one of the world's greatest plagues. However, predictable secular trends in the AIDS epidemic make it likely that the number of cases of ocular complications of AIDS will increase substantially before they decrease. Ophthalmologists worldwide should be familiar with the diagnosis and management of cytomegalovirus retinitis - the most common ocular complication of AIDS - and should establish partnerships with physicians who are able to provide HAART. Research is needed to determine the optimal approach for managing cytomegalovirus retinitis in resource-constrained settings. PMID:18711266

  3. Antifungal prophylaxis during neutropenia and immunodeficiency.

    PubMed Central

    Lortholary, O; Dupont, B

    1997-01-01

    Fungal infections represent a major source of morbidity and mortality in patients with almost all types of immunodeficiencies. These infections may be nosocomial (aspergillosis) or community acquired (cryptococcosis), or both (candidiasis). Endemic mycoses such as histoplasmosis, coccidioidomycosis, and penicilliosis may infect many immunocompromised hosts in some geographic areas and thereby create major public health problems. With the wide availability of oral azoles, antifungal prophylactic strategies have been extensively developed. However, only a few well-designed studies involving strict criteria have been performed, mostly in patients with hematological malignancies or AIDS. In these situations, the best dose and duration of administration of the antifungal drug often remain to be determined. In high-risk neutropenic or bone marrow transplant patients, fluconazole is effective for the prevention of superficial and/or systemic candidal infections but is not always able to prolong overall survival and potentially selects less susceptible or resistant Candida spp. Primary prophylaxis against aspergillosis remains investigative. At present, no standard general recommendation for primary antifungal prophylaxis can be proposed for AIDS patients or transplant recipients. However, for persistently immunocompromised patients who previously experienced a noncandidal systemic fungal infection, prolonged suppressive antifungal therapy is often indicated to prevent a relapse. Better strategies for controlling immune deficiencies should also help to avoid some potentially life-threatening deep mycoses. When prescribing antifungal prophylaxis, physicians should be aware of the potential emergence of resistant strains, drug-drug interactions, and the cost. Well-designed, randomized, multicenter clinical trials in high-risk immunocompromised hosts are urgently needed to better define how to prevent severe invasive mycoses. PMID:9227863

  4. Frequency and clinical manifestations of patients with primary immunodeficiency disorders in Iran: update from the Iranian Primary Immunodeficiency Registry.

    PubMed

    Rezaei, Nima; Aghamohammadi, Asghar; Moin, Mostafa; Pourpak, Zahra; Movahedi, Masoud; Gharagozlou, Mohammad; Atarod, Lida; Ghazi, Bahram Mirsaeid; Isaeian, Anna; Mahmoudi, Maryam; Abolmaali, Kamran; Mansouri, Davoud; Arshi, Saba; Tarash, Naser Javaher; Sherkat, Roya; Akbari, Hedayat; Amin, Reza; Alborzi, Abdolvahab; Kashef, Sara; Farid, Reza; Mohammadzadeh, Iraj; Shabestari, Mehrnaz Sadeghi; Nabavi, Mohammad; Farhoudi, Abolhassan

    2006-11-01

    Primary immunodeficiency disorders (PID) are a heterogeneous group of diseases, characterized by an increased susceptibility to infections. A total of 930 patients (573 males and 357 females) are registered in Iranian PID Registry (IPIDR) during three decades. Predominantly antibody deficiencies were the most common (38.4%), followed by congenital defects of phagocyte number and/or function (28.3%), other well-defined immunodeficiency syndromes (17.7%), combined T- and B-cell immunodeficiencies (11.0%), complement deficiencies (2.4%), and diseases of immune dysregulation (2.3%). Common variable immunodeficiency was the most frequent disorder (20.8%), followed by chronic granulomatous disease, ataxia-telangiectasia, btk deficiency, selective IgA deficiency, and T-B-severe combined immunodeficiency. The frequency of other PID disorders was less than 50 in number (<5%). There is an increasing trend in recognition of more PID in the recent years. Construction of such registry is not only important for its epidemiological aspect but also for its role in increasing the physician's knowledge about such disorders. PMID:17024564

  5. Generalized varicella in severe combined immunodeficiency with B lymphocytes.

    PubMed

    Timár, L; Budai, J; Szigeti, R

    1981-01-01

    A six-month-old male infant, whose elder brother had died of progressive vaccinia due to combined immunodeficiency, contracted varicella-zoster infection, and died of disseminated varicella ten days after onset of the disease. As with his elder brother, the blood levels of immunoglobulins were normal, and specific varicella antibodies appeared in his serum, although in low concentrations. His T-lymphocytes, although their number was subnormal, could be stimulated with phytohaemagglutinin, and production of migration inhibitory factor could also be demonstrated. The necropsy confirmed thymic dysplasia. In addition to histological changes, severe combined immunodeficiency and foci of malignant lymphoma were present. On this basis the disease was classified, according to the WHO recommendations, as severe combined immunodeficiency with B lymphocytes, complicated by malignant lymphoma. PMID:6979157

  6. Immunodeficiency and autoimmune enterocolopathy linked to NFAT5 haploinsufficiency.

    PubMed

    Boland, Brigid S; Widjaja, Christella E; Banno, Asoka; Zhang, Bing; Kim, Stephanie H; Stoven, Samantha; Peterson, Michael R; Jones, Marilyn C; Su, H Irene; Crowe, Sheila E; Bui, Jack D; Ho, Samuel B; Okugawa, Yoshinaga; Goel, Ajay; Marietta, Eric V; Khosroheidari, Mahdieh; Jepsen, Kristen; Aramburu, Jose; López-Rodríguez, Cristina; Sandborn, William J; Murray, Joseph A; Harismendy, Olivier; Chang, John T

    2015-03-15

    The link between autoimmune diseases and primary immunodeficiency syndromes has been increasingly appreciated. Immunologic evaluation of a young man with autoimmune enterocolopathy and unexplained infections revealed evidence of immunodeficiency, including IgG subclass deficiency, impaired Ag-induced lymphocyte proliferation, reduced cytokine production by CD8(+) T lymphocytes, and decreased numbers of NK cells. Genetic evaluation identified haploinsufficiency of NFAT5, a transcription factor regulating immune cell function and cellular adaptation to hyperosmotic stress, as a possible cause of this syndrome. Inhibition or deletion of NFAT5 in normal human and murine cells recapitulated several of the immune deficits identified in the patient. These results provide evidence of a primary immunodeficiency disorder associated with organ-specific autoimmunity linked to NFAT5 deficiency. PMID:25667416

  7. Neurosyphilis in a Man with Human Immunodeficiency Virus

    PubMed Central

    Sadeghani, Khosro; Kallini, Joseph R.

    2014-01-01

    The authors describe a 33-year-old man with human immunodeficiency virus who developed erythematous macules on the palms and soles with subsequent headaches, papilledema, and iritis. They review the salient characteristics of neurosyphilis with a focus on human immunodeficiency virus-positive individuals. The incidence of syphilis has increased since the year 2000 in African Americans, Hispanics, and men who have sex with men. Treponema pallidum is the causative agent of this disease—a fastidious, slowly growing, microaerophilic spirochete. Sexual contact is the most common mode of transmission. The rapid plasma reagin, Venereal Disease Research Laboratory assay, and fluorescent treponemal antibody absorption assay are commonly used to diagnose syphilis. The mainstay treatment is penicillin. Special considerations exist in the natural history and management of syphilis in the setting of human immunodeficiency virus. PMID:25161759

  8. Immunoglobulins and secretory component in the external secretions of foals with combined immunodeficiency.

    PubMed Central

    Buening, G M; Perryman, L E; McGuire, T C

    1978-01-01

    Nasal washings and tears were collected from seven Arabian foals with combined immunodeficiency and nine normal foals. The major immunoglobulin in the external secretions of normal foals over 2 months of age was secretory immunoglobulin A, whereas foals with combined immunodeficiency lacked this immunoglobulin. The external secretions of both normal and immunodeficient foals contained free secretory component at birth. Images PMID:631895

  9. Vaccine-associated Paralytic Poliomyelitis in Immunodeficient Children, Iran, 1995–2008

    PubMed Central

    Shahmahmoodi, Shohreh; Mamishi, Setareh; Aghamohammadi, Asghar; Aghazadeh, Nessa; Tabatabaie, Hamideh; Gooya, Mohammad Mehdi; Zahraei, Seyed Mohsen; Mousavi, Taha; Yousefi, Maryam; Farrokhi, Kobra; Mohammadpour, Masoud; Ashrafi, Mahmoud Reza; Nategh, Rakhshandeh

    2010-01-01

    To determine the prevalence of vaccine-associated paralytic poliomyelitis (VAPP) in immunodeficient infants, we reviewed all documented cases caused by immunodeficiency-associated vaccine-derived polioviruses in Iran from 1995 through 2008. Changing to an inactivated polio vaccine vaccination schedule and introduction of screening of neonates for immunodeficiencies could reduce the risk for VAPP infection. PMID:20587188

  10. Neutral evolution of mutational robustness

    PubMed Central

    van Nimwegen, Erik; Crutchfield, James P.; Huynen, Martijn

    1999-01-01

    We introduce and analyze a general model of a population evolving over a network of selectively neutral genotypes. We show that the population’s limit distribution on the neutral network is solely determined by the network topology and given by the principal eigenvector of the network’s adjacency matrix. Moreover, the average number of neutral mutant neighbors per individual is given by the matrix spectral radius. These results quantify the extent to which populations evolve mutational robustness—the insensitivity of the phenotype to mutations—and thus reduce genetic load. Because the average neutrality is independent of evolutionary parameters—such as mutation rate, population size, and selective advantage—one can infer global statistics of neutral network topology by using simple population data available from in vitro or in vivo evolution. Populations evolving on neutral networks of RNA secondary structures show excellent agreement with our theoretical predictions. PMID:10449760

  11. Neutral evolution of mutational robustness.

    PubMed

    van Nimwegen, E; Crutchfield, J P; Huynen, M

    1999-08-17

    We introduce and analyze a general model of a population evolving over a network of selectively neutral genotypes. We show that the population's limit distribution on the neutral network is solely determined by the network topology and given by the principal eigenvector of the network's adjacency matrix. Moreover, the average number of neutral mutant neighbors per individual is given by the matrix spectral radius. These results quantify the extent to which populations evolve mutational robustness-the insensitivity of the phenotype to mutations-and thus reduce genetic load. Because the average neutrality is independent of evolutionary parameters-such as mutation rate, population size, and selective advantage-one can infer global statistics of neutral network topology by using simple population data available from in vitro or in vivo evolution. Populations evolving on neutral networks of RNA secondary structures show excellent agreement with our theoretical predictions. PMID:10449760

  12. Common variable immunodeficiency disorder - An uncommon cause for bronchiectasis

    PubMed Central

    Panigrahi, Manoj Kumar

    2014-01-01

    Bronchiectasis continues to be a common respiratory problem of varied etiology. Common variable immunodeficiency disorder (CVID) is an uncommon cause for bronchiectasis. However, the prevalence of bronchiectasis remains very high in patients with CVID. This remains largely an underdiagnosed entity as primary immunodeficiency is not suspected in adults as a cause of bronchiectasis and hence, serum immunoglobulin (Ig) levels are not measured routinely. In addition to bronchiectasis, patients with CVID usually present with various extrapulmonary symptoms. I report here a case of young man who presented with bronchiectasis and multisystem complains who was diagnosed as CVID. PMID:25378851

  13. Neuroleptic malignant syndrome in the acquired immunodeficiency syndrome.

    PubMed Central

    Hernández, J. L.; Palacios-Araus, L.; Echevarría, S.; Herrán, A.; Campo, J. F.; Riancho, J. A.

    1997-01-01

    Patients infected by the human immunodeficiency virus are predisposed to many infectious and noninfectious complications and often receive a variety of drugs. Furthermore, they seem to have a particular susceptibility to idiosyncratic adverse drug reactions. It is therefore surprising that only a few cases of the neuroleptic malignant syndrome have been described in patients with the acquired immunodeficiency syndrome. A high index of suspicion is required to diagnose the neuroleptic malignant syndrome in these patients, as its usual manifestations, including fever and altered consciousness, are frequently attributed to an underlying infection. PMID:9497946

  14. A proposed neutral line signature

    NASA Technical Reports Server (NTRS)

    Doxas, I.; Speiser, T. W.; Dusenbery, P. B.; Horton, W.

    1992-01-01

    An identifying signature is proposed for the existence and location of the neutral line in the magnetotail. The signature, abrupt density, and temperature changes in the Earthtail direction, was first discovered in test particle simulations. Such temperature variations have been observed in ISEE data (Huang et. al. 1992), but their connection to the possible existence of a neutral line in the tail has not yet been established. The proposed signature develops earlier than the ion velocity space ridge of Martin and Speiser (1988), but can only be seen by spacecraft in the vicinity of the neutral line, while the latter can locate a neutral line remotely.

  15. Chemistry of carotenoid neutral radicals.

    PubMed

    Ligia Focsan, A; Magyar, Adam; Kispert, Lowell D

    2015-04-15

    Proton loss from the carotenoid radical cations (Car(+)) to form neutral radicals (#Car) was investigated by numerous electrochemical, EPR, ENDOR and DFT studies described herein. The radical cation and neutral radicals were formed in solution electrochemically and stabilized on solid silica-alumina and MCM-41 matrices. Carotenoid neutral radicals were recently identified in Arabidopsis thaliana plant and photosystem II samples. Deprotonation at the terminal ends of a zeaxanthin radical cation could provide a secondary photoprotection pathway which involves quenching excited state chlorophyll by the long-lived zeaxanthin neutral radicals formed. PMID:25687648

  16. Smallpox vaccination and patients with human immunodeficiency virus infection or acquired immunodeficiency syndrome.

    PubMed

    Bartlett, John G

    2003-02-15

    Smallpox vaccination strategies are evolving rapidly and have important implications for human immunodeficiency virus (HIV)-infected persons. Cell-mediated immunity is important for controlling both smallpox and vaccinia. For smallpox, the concern is a substantial increase in the associated mortality rate, which is 30% among healthy persons. For smallpox vaccination, the concern is progressive vaccinia, which is usually lethal but relatively uncommon. The risks associated with both smallpox and vaccinia viruses probably correlate with CD4 cell count, and, as a corollary, the best protection against infection with each is presumably immune reconstitution. It appears that all vaccinations will be voluntary, with 2 recommendations: (1) HIV-infected persons will be advised to decline preemptive vaccination, and (2) in the event of a bioterrorism attack involving smallpox, HIV-infected patients with exposures will be advised to receive vaccine. PMID:12567305

  17. The Selection of Low Envelope Glycoprotein Reactivity to Soluble CD4 and Cold during Simian-Human Immunodeficiency Virus Infection of Rhesus Macaques

    PubMed Central

    McGee, Kathleen; Haim, Hillel; Korioth-Schmitz, Birgit; Espy, Nicole; Javanbakht, Hassan; Letvin, Norman

    2014-01-01

    Envelope glycoprotein (Env) reactivity (ER) describes the propensity of human immunodeficiency virus type 1 (HIV-1) Env to change conformation from the metastable unliganded state in response to the binding of ligands (antibodies and soluble CD4 [sCD4]) or incubation in the cold. To investigate Env properties that favor in vivo persistence, we inoculated rhesus macaques with three closely related CCR5-tropic simian-human immunodeficiency viruses (SHIVs) that differ in ER to cold (ERcold) and ER to sCD4 (ERsCD4); these SHIVs were neutralized by antibodies equivalently and thus were similar in ERantibody. All three SHIVs achieved high levels of acute viremia in the monkeys without alteration of their Env sequences, indicating that neither ERcold nor ERsCD4 significantly influences the establishment of infection. Between 14 and 100 days following infection, viruses with high ERcold and ERsCD4 were counterselected. Remarkably, the virus variant with low ERcold and low ERsCD4 did not elicit a neutralizing antibody response against the infecting virus, despite the generation of high levels of anti-Env antibodies in the infected monkeys. All viruses that achieved persistent viremia escaped from any autologous neutralizing antibodies and exhibited low ERcold and low ERsCD4. One set of gp120 changes determined the decrease in ERcold and ERsCD4, and a different set of gp120 changes determined resistance to autologous neutralizing antibodies. Each set of changes contributed to a reduction in Env-mediated entry. During infection of monkeys, any Env replication fitness costs associated with decreases in ERcold and ERsCD4 may be offset by minimizing the elicitation of autologous neutralizing antibodies. PMID:24131720

  18. The selection of low envelope glycoprotein reactivity to soluble CD4 and cold during simian-human immunodeficiency virus infection of rhesus macaques.

    PubMed

    McGee, Kathleen; Haim, Hillel; Korioth-Schmitz, Birgit; Espy, Nicole; Javanbakht, Hassan; Letvin, Norman; Sodroski, Joseph

    2014-01-01

    Envelope glycoprotein (Env) reactivity (ER) describes the propensity of human immunodeficiency virus type 1 (HIV-1) Env to change conformation from the metastable unliganded state in response to the binding of ligands (antibodies and soluble CD4 [sCD4]) or incubation in the cold. To investigate Env properties that favor in vivo persistence, we inoculated rhesus macaques with three closely related CCR5-tropic simian-human immunodeficiency viruses (SHIVs) that differ in ER to cold (ERcold) and ER to sCD4 (ERsCD4); these SHIVs were neutralized by antibodies equivalently and thus were similar in ERantibody. All three SHIVs achieved high levels of acute viremia in the monkeys without alteration of their Env sequences, indicating that neither ERcold nor ERsCD4 significantly influences the establishment of infection. Between 14 and 100 days following infection, viruses with high ERcold and ERsCD4 were counterselected. Remarkably, the virus variant with low ERcold and low ERsCD4 did not elicit a neutralizing antibody response against the infecting virus, despite the generation of high levels of anti-Env antibodies in the infected monkeys. All viruses that achieved persistent viremia escaped from any autologous neutralizing antibodies and exhibited low ERcold and low ERsCD4. One set of gp120 changes determined the decrease in ERcold and ERsCD4, and a different set of gp120 changes determined resistance to autologous neutralizing antibodies. Each set of changes contributed to a reduction in Env-mediated entry. During infection of monkeys, any Env replication fitness costs associated with decreases in ERcold and ERsCD4 may be offset by minimizing the elicitation of autologous neutralizing antibodies. PMID:24131720

  19. Cryoprotectant toxicity neutralization.

    PubMed

    Fahy, Gregory M

    2010-07-01

    Cryoprotectant toxicity is a fundamental limiting factor for the successful cryopreservation of living systems by both freezing and vitrification, and the ability to negate it would be attractive. Past attempts to demonstrate "cryoprotectant toxicity neutralization" (CTN) have had many ups and downs. First convincingly introduced by Baxter and Lathe in 1971, the concept that certain amides can block toxic effects of dimethyl sulfoxide (Me(2)SO) was contradicted by direct experiments in 1990. But in 1995, the opposite mode of CTN, in which Me(2)SO blocked the damaging effects of formamide, was robustly demonstrated. Recent experiments have verified the original 1995 results and extended them to urea and acetamide, but no CTN was detected for N-methylamides (N-methylformamide, N,N-dimethylformamide, and N-methylacetamide). On the theory that the latter amides and acetamide might serve as low-toxicity structural analogs of formamide, urea, or Me(2)SO, competition experiments were carried out between them and formamide or urea, but CTN was not observed for these amide-amide systems. The idea that the N-methylamides might have non-specific rather than specific toxicity was supported by the fact that the concentrations of these amides that cause toxicity are similar to the concentrations that denature model proteins. Clear examples of neutralization of the toxicity of glycerol, propylene glycol, ethylene glycol, or Me(2)SO are presently lacking, but effects of the latter that depend on sulfhydryl oxidation have been reversed with reducing agents. In summary, CTN is a useful phenomenon with significant theoretical and practical implications. PMID:19501081

  20. Distinct Evolutionary Pressures Underlie Diversity in Simian Immunodeficiency Virus and Human Immunodeficiency Virus Lineages

    PubMed Central

    Apetrei, Cristian; Santiago, Mario L.; Li, Yingying; Gautam, Rajeev; Pandrea, Ivona; Shaw, George M.; Hahn, Beatrice H.; Letvin, Norman L.; Nabel, Gary J.

    2012-01-01

    Simian immunodeficiency virus (SIV) infection of rhesus macaques causes immune depletion and disease closely resembling human AIDS and is well recognized as the most relevant animal model for the human disease. Experimental investigations of viral pathogenesis and vaccine protection primarily involve a limited set of related viruses originating in sooty mangabeys (SIVsmm). The diversity of human immunodeficiency virus type 1 (HIV-1) has evolved in humans in about a century; in contrast, SIV isolates used in the macaque model evolved in sooty mangabeys over millennia. To investigate the possible consequences of such different evolutionary histories for selection pressures and observed diversity in SIVsmm and HIV-1, we isolated, sequenced, and analyzed 20 independent isolates of SIVsmm, including representatives of 7 distinct clades of viruses isolated from natural infection. We found SIVsmm diversity to be lower overall than HIV-1 M group diversity. Reduced positive selection (i.e., less diversifying evolution) was evident in extended regions of SIVsmm proteins, most notably in Gag p27 and Env gp120. In addition, the relative diversities of proteins in the two lineages were distinct: SIVsmm Env and Gag were much less diverse than their HIV-1 counterparts. This may be explained by lower SIV-directed immune activity in mangabeys relative to HIV-1-directed immunity in humans. These findings add an additional layer of complexity to the interpretation and, potentially, to the predictive utility of the SIV/macaque model, and they highlight the unique features of human and simian lentiviral evolution that inform studies of pathogenesis and strategies for AIDS vaccine design. PMID:23055550

  1. MAIN CHAMBER NEUTRAL PRESSURE IN

    E-print Network

    Pitcher, C. S.

    MAIN CHAMBER NEUTRAL PRESSURE IN ALCATOR C-MOD AND JET C S Pitcher, S K Erents*, W Fundamenski*, B on Controlled Fusion and Plasma Physics 18 ­ 22 June 1999, Madeira, Portugal MAIN CHAMBER NEUTRAL PRESSURE Science Centre, Abingdon, Oxon OX14 3DB,UK #12;(1) Introduction · main chamber gas can have a number

  2. Frequent Intratype Neutralization by Plasma Immunoglobulin A Identified in HIV Type 2 Infection

    PubMed Central

    Månsson, Fredrik; Palm, Angelica A.; Vincic, Elzbieta; da Silva, Zacarias; Medstrand, Patrik; Norrgren, Hans; Fenyö, Eva Maria; Jansson, Marianne

    2013-01-01

    Abstract Human immunodeficiency virus type 2 (HIV-2) is less transmissible and less pathogenic compared to HIV-1 and, when matched for CD4+ T cell count, the plasma viral load in HIV-2-infected individuals is approximately one log lower than in HIV-1-infected individuals. The explanation for these observations is elusive, but differences in virus controlling immunity generated in the two infections may be contributing factors. In the present study, we investigated neutralization by immunoglobulin A (IgA), in parallel with IgG, purified from plasma of HIV-1, HIV-2, and HIV-1/HIV-2 dually (HIV-D) infected individuals. Neutralization was analyzed against HIV-1 and HIV-2 isolates using a plaque reduction assay. In HIV-2 infection, intratype-specific neutralization by IgA was frequently detected, although at a lesser magnitude then the corresponding IgG neutralizing titers. In contrast, neutralization by IgA could rarely be demonstrated in HIV-1 infection despite similar plasma IgA levels in both infections. In addition, IgA and IgG of HIV-D plasma neutralized the HIV-2 isolate more potently than the HIV-1 isolate, suggesting that the difference between neutralizing activity of plasma IgA and IgG depends on the virus itself. Taken together, these findings suggest that both IgA and IgG add to the potent intratype neutralizing activity detected in HIV-2 plasma, which may contribute to virus control in HIV-2 infection. PMID:23088167

  3. Spreading of Saturn's Neutral Torus

    NASA Astrophysics Data System (ADS)

    Cassidy, T. A.; Johnson, R. E.; Kuo, C.

    2009-12-01

    The H2O vapor ejected from Enceladus' south pole forms a Saturn-encircling cloud of neutrals and plasma. Two decades of OH cloud modeling and observations suggested that H2O, and its dissociation and ionization products are spread throughout the Saturnian system primarily by magnetospheric plasma/neutral interactions (e.g., Johnson et al., APJ, 2006). In recent years, Cassini UVIS data has shown even broader O and H clouds that are not reproduced by previous models. Using a Direct Simulation Monte Carlo model of the neutral cloud we have found that the neutral-neutral collisions are key to explaining the unexpected breadth of the O cloud (See also: Farmer, Icarus, 2009). We will also discuss the cloud's curious H2O maser emission (Pogrebenko et al., 2009), which, we hypothesize, is a consequence of electron impact excitation.

  4. The EUROclass trial: Defining subgroups in common variable immunodeficiency

    Microsoft Academic Search

    Claudia Wehr; Teemu Kivioja; Christian Schmitt; Berne Ferry; Torsten Witte; Marcela Vlkova; Manuel Hernandez; Drahomira Detkova; Philip R. Bos; Ulrich Baumann; Sigune Goldacker; Sylvia Gutenberger; Michael. Schlesier; Florence Bergeron-van der Cruyssen; Magali Le Garff; Patrice Debré; Roland Jacobs; John Jones; Elizabeth Bateman; Jiri Litzman; P. Martin van Hagen; Reinhold E. Schmidt; Vojtech Thon; Isabella Quinti; Teresa Espanol; A. David Webster; Helen Chapel; Mauno Vihinen; Eric Oksenhendler; Hans Hartmut Peter; Klaus Warnatz

    The heterogeneity of common variable immunodeficiency (CVID) calls for a clas- sification addressing pathogenic mecha- nisms as well as clinical relevance. This European multicenter trial was initiated to develop a consensus of 2 existing classi- fication schemes based on flowcytomet- ric B-cell phenotyping and the clinical course. The clinical evaluation of 303 patients with the established diagno- sis of CVID

  5. Human immunodeficiency virus protease inhibitors and risk for peripheral neuropathy

    Microsoft Academic Search

    Ronald J. Ellis; Jennifer Marquie-Beck; Patrick Delaney; Terry Alexander; David B. Clifford; Justin C. McArthur; David M. Simpson; Christopher Ake; Ann C. Collier; Benjamin B. Gelman; J. Allen McCutchan; Susan Morgello; Igor Grant

    2008-01-01

    Objective: Two recent analyses found that exposure to protease inhibitors (PIs) in the context of antiretroviral (ARV) therapy increased the risk for distal sensory polyneuropathy (DSPN) in subjects with human immunodeficiency virus (HIV) infection. These findings were supported by an in vitro model in which PI exposure produced neurite retraction and process loss in dorsal root ganglion sensory neurons. Confirmation

  6. Human Immunodeficiency Virus Infection Prevention: Strategies for Clinicians

    Microsoft Academic Search

    Tanya Schreibman; Gerald Friedland

    2003-01-01

    The complexity of the epidemic of human immunodeficiency virus (HIV) infection has made the creation of effective prevention programs an evolving and challenging task. Prevention of new HIV infections is an issue of increasing importance as the prevalence of HIV infection continues to increase. The integration of prevention and clinical care is recognized as a key element of future prevention

  7. Vaginal and rectal infection of cats with feline immunodeficiency virus

    Microsoft Academic Search

    Sarah A. Bishop; Christopher R. Stokes; Timothy J. Gruffydd-Jones; Christine V. Whiting; David A. Harbour

    1996-01-01

    The objective of this study was to examine the potential of vaginal and rectal mucosal routes for feline immunodeficiency virus (FIV) uptake and infection, as a model of mucosal HIV infection, and to determine the fate of virus at these mucosal sites following transmission of infection. SPF cats were exposed to FIV isolates (PET, GL-8, T637), administered as either cell-associated

  8. Incidence of cryptosporidiosis in immunodeficient cancer patients in Egypt.

    PubMed

    Hassan, Soad I; Sabry, Hoda; Amer, Neimat M; Shalaby, Maysa A; Mohamed, Nahed A; Gaballah, Hussien

    2002-04-01

    A coproprotozoal study was carried out on 63 patients suffering from malignancy. The majority had cancer of haemopoietic system. All patients were under chemotherapy and included: Group A (33 children) and Group B (30 adults) of whom 20 immunocompetent diarrhoeic patients of matched age and sex were considered as controls. Stool samples were examined by merthiolate iodine-formaldehyde concentration technique (MIF). Modified Zeihl-Neelsen (ZN) stain was performed for Cryptosporidium oocysts. Detection of Cryptosporidium coproantigen by enzyme-linked immunoassay test (Ridascreen test), was used. Immunoglobulins (IgG, IgM, IgE & IgA), C3, C4 and CD4:CD8 ratio, were measured. According to their levels 25 out of 63 patients had both humoral and cellular immunodeficiency. The incidence of Cryptosporidium in cancer patients was 23.8%, while it was 37.7% and 91% in children and adults immunodeficient patients, respectively. ZN stain was able in diagnosed Cryptosporidium in 13 out of 35 immunodeficient cases while ELISA detected only 11 cases. Cryptosporidium infection in immunodeficient cancer patients had significantly more frequent and prolonged duration of diarrhoea than in negative ones. PMID:12049267

  9. The Presidential Commission on the Human Immunodeficiency Virus Epidemic Report.

    ERIC Educational Resources Information Center

    Presidential Commission on the Human Immunodeficiency Virus Epidemic, Washington, DC.

    This document presents findings of the Presidential Commission on the Human Immunodeficiency Virus (HIV) epidemic. The executive summary lists 20 major findings and recommendations which together comprise a comprehensive national strategy for managing the HIV epidemic. The commission recommends: (1) replacement of the obsolete term "AIDS"…

  10. Serologic evidence for bovine immunodeficiency virus infection in France

    Microsoft Academic Search

    B. Polack; I. Schwartz; M. Berthelemy; C. Belloc; G. Manet; A. Vuillaume; T. Baron; M. A. Gonda; D. Lévy

    1996-01-01

    We report herein on the first serologic detection of antibodies to bovine immunodeficiency virus (BIV) in France. Serum samples from dairy and beef cattle from southwestern and western France (Landes and Vendée) were tested using a western blot assay with a recombinant 53 kDa gag precursor derived from the Louisiana BIV R29 isolate. We performed our study on the oldest

  11. The Human Immunodeficiency Virus: Infectivity and Mechanisms of Pathogenesis.

    ERIC Educational Resources Information Center

    Fauci, Anthony S.

    1988-01-01

    Discusses how the infection of the human immunodeficiency virus (HIV) results in a profound immunosuppression due predominantly to a selective depletion of helper/inducer T lymphocytes that express the receptor for the virus, as well as neuropsychiatric abnormalities in the brain. (TW)

  12. Molecular characterization and heterogeneity of feline immunodeficiency virus isolates

    Microsoft Academic Search

    N. Maki; T. Miyazawa; M. Fukasawa; A. Hasegawa; M. Hayami; K. Miki; T. Mikami

    1992-01-01

    Summary We have molecularly cloned the complete genomic DNA of TM2 strain of feline immunodeficiency virus (FIV) isolated in Japan and compared its nucleotide and the deduced amino acid sequence with those of previously described U.S. isolates, FIV Petaluma and FIV PPR. The infectious molecular clone of FIV TM2 is different from FIV Petaluma in host cell range; the clone

  13. Subject Control of the Literature of Acquired Immunodeficiency Syndrome (AIDS).

    ERIC Educational Resources Information Center

    Bierbaum, Esther Green; And Others

    1992-01-01

    Describes a study that analyzed the Medical Subject Headings (MeSH) terms used to index the literature of Acquired Immunodeficiency Syndrome (AIDS). Subject access to the AIDSLINE database developed by the National Library of Medicine (NLM) is examined, and changes in subject headings that reflect the growth of the field are analyzed. (12…

  14. Immune Suppression in Calves with Bovine Immunodeficiency Virus

    Microsoft Academic Search

    SHUCHENG ZHANG; CHARLES WOOD; WENZHI XUE; SAMUEL M. KRUKENBERG; QIMIN CHEN; ANDHARISH C. MINOCHA

    1997-01-01

    The present study was designed to evaluate the effect of bovine immunodeficiency virus (BIV) infection on immune functions and possible interactions between BIV and other bovine viruses in calves. Ten calves were inoculated intravenously with BIV, andfive served as controls. An increased lymphocyte proliferation to BIV gagprotein was demonstrated 2 to 6 weeks after BIV inoculation (P< 0.05). Lymphocyte subset

  15. Massive neuronal destruction in human immunodeficiency virus (HIV) encephalitis

    Microsoft Academic Search

    F. Giangaspero; E. Scanabissi; M. C. Baldacci; C. M. Betts

    1989-01-01

    Human immunodeficiency virus (HIV) encephalitis in children with AIDS includes a diffuse white matter disease associated with an inflammatory cell infiltrate that features multinucleated giant cells. Cerebral cortex is relatively preserved and only focal loss of Purkinje cells in the cerebellum has been observed. We describe a case of encephalitis in a child with AIDS in which there was massive

  16. Human Immunodeficiency Virus Risk Behavior Among Female Substance Abusers

    Microsoft Academic Search

    Susan E. Ramsey; Kathryn M. Bell; Patricia A. Engler

    2010-01-01

    HIV is an increasingly critical and costly health problem for American women. Substance use plays a major role in human immunodeficiency virus (HIV) infection in women. There are several plausible explanations for the association between substance use and HIV risk behavior. Pregnant substance abusers are a population deserving special attention given the prevalence of risk behavior in this population and

  17. Frequent transmission of immunodeficiency viruses among bobcats and pumas

    USGS Publications Warehouse

    Franklin, S.P.; Troyer, J.L.; TerWee, J.A.; Lyren, L.M.; Boyce, W.M.; Riley, S.P.D.; Roelke, M.E.; Crooks, K.R.; VandeWoude, S.

    2007-01-01

    With the exception of human immunodeficiency virus (HIV), which emerged in humans after cross-species transmissions of simian immunodeficiency viruses from nonhuman primates, immunodeficiency viruses of the family Lentiviridae represent species-specific viruses that rarely cross species barriers to infect new hosts. Among the Felidae, numerous immunodeficiency-like lentiviruses have been documented, but only a few cross-species transmissions have been recorded, and these have not been perpetuated in the recipient species. Lentivirus seroprevalence was determined for 79 bobcats (Lynx rufus) and 31 pumas (Puma concolor) from well-defined populations in Southern California. Partial genomic sequences were subsequently obtained from 18 and 12 seropositive bobcats and pumas, respectively. Genotypes were analyzed for phylogenic relatedness and genotypic composition among the study set and archived feline lentivirus sequences. This investigation of feline immunodeficiency virus infection in bobcats and pumas of Southern California provides evidence that cross-species infection has occurred frequently among these animals. The data suggest that transmission has occurred in multiple locations and are most consistent with the spread of the virus from bobcats to pumas. Although the ultimate causes remain unknown, these transmission events may occur as a result of puma predation on bobcats, a situation similar to that which fostered transmission of HIV to humans, and likely represent the emergence of a lentivirus with relaxed barriers to cross-species transmission. This unusual observation provides a valuable opportunity to evaluate the ecological, behavioral, and molecular conditions that favor repeated transmissions and persistence of lentivirus between species. Copyright ?? 2007, American Society for Microbiology. All Rights Reserved.

  18. Protective Levels of Diphtheria-Neutralizing Antibody Induced in Healthy Volunteers by Unilateral Priming-Boosting Intranasal Immunization Associated with Restricted Ipsilateral Mucosal Secretory Immunoglobulin A

    Microsoft Academic Search

    Kingston H. G. Mills; Catherine Cosgrove; Edel A. McNeela; Amy Sexton; Rafaela Giemza; Inderjit Jabbal-Gill; Anne Church; Wu Lin; Lisbeth Illum; Audino Podda; Rino Rappuoli; Mariagrazia Pizza; George E. Griffin; David J. M. Lewis

    2003-01-01

    Subunit intranasal vaccines offer the prospect of inducing combined systemic-mucosal immunity against mucosally transmitted infections such as human immunodeficiency virus. However, although human studies have demonstrated the induction of active immunity, secretory immunoglobulin A (sIgA) responses are variable, and no study has demonstrated protection by accepted vaccine-licensing criteria as measured by direct toxin-neutralizing activity. Using the genetically inactivated mutant diphtheria

  19. Neutral Sphingomyelinase 2

    PubMed Central

    Filosto, Simone; Castillo, Sianna; Danielson, Aaron; Franzi, Lisa; Khan, Elaine; Kenyon, Nick; Last, Jerold; Pinkerton, Kent; Tuder, Rubin; Goldkorn, Tzipora

    2011-01-01

    Chronic obstructive pulmonary disease (COPD) is caused by exposure to cigarette smoke (CS). One mechanism of CS-induced lung injury is aberrant generation of ceramide, which leads to elevated apoptosis of epithelial and endothelial cells in the alveolar spaces. Recently, we discovered that CS-induced ceramide generation and apoptosis in pulmonary cells is governed by neutral sphingomyelinase (nSMase) 2. In the current experiments, we expanded our studies to investigate whether nSMase2 governs ceramide generation and apoptosis in vivo using rodent and human models of CS-induced lung injury. We found that exposure of mice or rats to CS leads to colocalizing elevations of ceramide levels and terminal deoxynucleotidyl transferase mediated X-dUTP nick end labeling–positive cells in lung tissues. These increases are nSMase2 dependent, and are abrogated by treatment with N-acetyl cysteine or anti-nSMase2 small interfering RNA (siRNA). We further showed that mice that are heterozygous for nSMase2 demonstrate significant decrease in ceramide generation after CS exposure, whereas acidic sphingomyelinase (aSMase) knockout mice maintain wild-type ceramide levels, confirming our previous findings (in human airway epithelial cells) that only nSMase2, and not aSMase, is activated by CS exposure. Lastly, we found that lung tissues from patients with emphysema (smokers) display significantly higher levels of nSMase2 expression compared with lung tissues from healthy control subjects. Taken together, these data establish the central in vivo role of nSMase2 in ceramide generation, aberrant apoptosis, and lung injury under CS exposure, underscoring its promise as a novel target for the prevention of CS-induced airspace destruction. PMID:20448054

  20. Nonneutralizing Antibodies Induced by the HIV-1 gp41 NHR Domain Gain Neutralizing Activity in the Presence of the HIV Fusion Inhibitor Enfuvirtide: a Potential Therapeutic Vaccine Strategy.

    PubMed

    Wang, Qian; Bi, Wenwen; Zhu, Xiaojie; Li, Haoyang; Qi, Qianqian; Yu, Fei; Lu, Lu; Jiang, Shibo

    2015-07-01

    A key barrier against developing preventive and therapeutic human immunodeficiency virus (HIV) vaccines is the inability of viral envelope glycoproteins to elicit broad and potent neutralizing antibodies. However, in the presence of fusion inhibitor enfuvirtide, we show that the nonneutralizing antibodies induced by the HIV type 1 (HIV-1) gp41 N-terminal heptad repeat (NHR) domain (N63) exhibit potent and broad neutralizing activity against laboratory-adapted HIV-1 strains, including the drug-resistant variants, and primary HIV-1 isolates with different subtypes, suggesting the potential of developing gp41-targeted HIV therapeutic vaccines. PMID:25903343

  1. Increased suppressor T cells in probable transmitters of human immunodeficiency virus infection.

    PubMed

    Seage, G R; Horsburgh, C R; Hardy, A M; Mayer, K H; Barry, M A; Groopman, J E; Jaffe, H W; Lamb, G A

    1989-12-01

    To evaluate behavioral and immunologic factors related to transmission of human immunodeficiency virus (HIV) by homosexual intercourse, we studied a population of 329 homosexual/bisexual men (155 partner-pairs) seen in a community health center and medical outpatient clinic. Logistic regression analysis showed that behavioral risk factors for infection in the 130 HIV-infected men included: receptive anal intercourse (OR 4.6, 95% CI-1.8, 12.1); receptive fisting (OR 2.5, CI-1.1, 7.0); nitrite use (OR 2.3, CI-1.2, 4.6); history of gonorrhea or syphilis (OR 2.3, CI-1.4, 3.9); and history of sexual contact with men from areas with many AIDS cases (OR 1.9, CI-1.0, 3.5). Comparing seven men who were probable transmitters of HIV and 11 men who had not transmitted HIV to their uninfected partners despite unprotected insertive anal intercourse, we found no differences in HIV isolation from peripheral blood mononuclear cells, circulating HIV antigen detection, or presence of neutralizing antibody to HIV. Helper T-cell numbers were not significantly different between the two groups, but transmitters had more suppressor T-cells than did nontransmitters. PMID:2530906

  2. Serological responses in chimpanzees inoculated with human immunodeficiency virus glycoprotein (gp120) subunit vaccine

    SciTech Connect

    Arthur, L.O.; Pyle, S.W.; Nara, P.L.; Bess, J.W. Jr.; Gonda, M.A.; Kelliher, J.C.; Gilden, R.V.; Robey, W.G.; Bolognesi, D.P.; Gallo, R.C.

    1987-12-01

    The major envelope glycoprotein of a human immunodeficiency virus (HIV) has been purified and was utilized as a prototype vaccine in chimpanzees. The 120,000-dalton glycoprotein (gp120) was purified from membranes of human T-lymphotropic virus (HTLV)-IIIB-infected cells and the final preparation contained low levels to no detectable HTLV-IIIB core antigen (p24) and low levels of endotoxin. Chimpanzees inoculated with gp120 responded by developing antibodies that precipitated radiolabeled gp120 and neutralized in vitro infection of HTLV-IIIB. Antibodies to HTLV-IIIB p24 were not detected in the gp120-immunized chimpanzees. Peripheral blood leukocytes from the vaccinated animals were examined for T4/sup +/ and T8/sup +/ cells, and no decrease in the T4/T8 ratio was found, indicating that immunization with a ligand (gp120) that binds to T4 has not detectable adverse effect on the population of T4/sup +/ cells. The only current animal model that can be reproducibly infected with HIV is the chimpanzee. Immunization of chimpanzees with HIV proteins will provide an experimental system for testing the effectiveness of prototype vaccines for preventing HIV infection in vivo.

  3. Effect of maternal CD4 + cell count, acquired immunodeficiency syndrome, and viral load on disease progression in infants with perinatally acquired human immunodeficiency virus type 1 infection

    Microsoft Academic Search

    Genevieve Lambert; Donald M. Thea; Vadim Pliner; Richard W. Steketee; Elaine J. Abrams; Pamela Matheson; Pauline A. Thomas; Barbara Greenberg; Teresa M. Brown; Marukh Bamji; Marcia L. Kalish

    1997-01-01

    Among a cohort of 152 infants perinatally infected with human immunodeficiency virus type 1, and their mothers, we correlated infant outcome with maternal CD4 + lymphocyte count and the presence of maternal acquired immunodeficiency syndrome near delivery. In a subset of 50 mother-infant pairs, we also correlated infant outcome with maternal quantitative viral burden as measured by the nucleic acid

  4. Inactivated simian immunodeficiency virus vaccine failed to protect rhesus macaques from intravenous or genital mucosal infection but delayed disease in intravenously exposed animals

    SciTech Connect

    Sutjipto, S.; Pedersen, N.C.; Miller, C.J.; Gardner, M.B.; Hanson, C.V.; Gettie, A.; Jennings, M.; Higgins, J.; Marx, P.A. (Univ. of California, Davis (USA))

    1990-05-01

    Eight rhesus macaques were immunized four times over a period of 8 months with a psoralen-UV-light-inactivated whole simian immunodeficiency virus vaccine adjuvanted with threonyl muramyl dipeptide. Eight unvaccinated control animals received adjuvant alone. Only the vaccinated animals made antibodies before challenge exposure to the viral core and envelope as determined by Western blotting (immunoblotting) and virus-neutralizing antibodies. Ten days after the final immunization, one-half of the vaccinated and nonvaccinated monkeys were challenged exposed intravenously (i.v.) and one-half were challenge exposed via the genital mucosa with virulent simian immunodeficiency virus. All of the nonvaccinated control monkeys became persistently infected. In spite of preexisting neutralizing antibodies and an anamnestic antibody response, all of the immunized monkeys also became persistently infected. However, there was evidence that the clinical course in immunized i.v. infected animals was delayed. All four mock-vaccinated i.v. challenge-exposed animals died with disease from 3 to 9 months postchallenge. In contrast, only one of four vaccinated i.v. challenge-exposed monkeys had died by 11 months postchallenge.

  5. Robust Neutralizing Antibodies Elicited by HIV-1 JRFL Envelope Glycoprotein Trimers in Nonhuman Primates

    PubMed Central

    Feng, Yu; Sharma, Shailendra Kumar; McKee, Krisha; Karlsson Hedestam, Gunilla B.; LaBranche, Celia C.; Montefiori, David C.; Mascola, John R.

    2013-01-01

    Host cell-mediated proteolytic cleavage of the human immunodeficiency virus type 1 (HIV-1) gp160 precursor glycoprotein into gp120 and gp41 subunits is required to generate fusion-competent envelope glycoprotein (Env) spikes. The gp120-directed broadly neutralizing monoclonal antibodies (bNabs) isolated from HIV-infected individuals efficiently recognize fully cleaved JRFL Env spikes; however, nonneutralizing gp120-directed monoclonal antibodies isolated from infected or vaccinated subjects recognize only uncleaved JRFL spikes. Therefore, as an immunogen, cleaved spikes that selectively present desired neutralizing epitopes to B cells may elicit cross-reactive neutralizing antibodies. Accordingly, we inoculated nonhuman primates (NHPs) with plasmid DNA encoding transmembrane-anchored, cleaved JRFL Env or by electroporation (EP). Priming with DNA expressing soluble, uncleaved gp140 trimers was included as a comparative experimental group of NHPs. DNA inoculation was followed by boosts with soluble JRFL gp140 trimers, and control NHPs were inoculated with soluble JRFL protein trimers without DNA priming. In the TZM-bl assay, elicitation of neutralizing antibodies against HIV-1 tier 1 isolates was robust following the protein boost. Neutralization of tier 2 isolates was detected, but only in animals primed with plasmid DNA and boosted with trimeric protein. Using the more sensitive A3R5 assay, consistent neutralization of both clade B and C tier 2 isolates was detected from all regimens assessed in the current study, exceeding levels achieved by our previous vaccine regimens in primates. Together, these data suggest a potential advantage of B cell priming followed by a rest interval and protein boosting to present JRFL Env spikes to the immune system to better generate HIV-1 cross-clade neutralizing antibodies. PMID:24067980

  6. Safety assessment, in vitro and in vivo, and pharmacokinetics of emivirine, a potent and selective nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1.

    PubMed

    Szczech, G M; Furman, P; Painter, G R; Barry, D W; Borroto-Esoda, K; Grizzle, T B; Blum, M R; Sommadossi, J; Endoh, R; Niwa, T; Yamamoto, M; Moxham, C

    2000-01-01

    Emivirine (EMV), formerly known as MKC-442, is 6-benzyl-1-(ethoxymethyl)-5-isopropyl-uracil, a novel nonnucleoside reverse transcriptase inhibitor that displays potent and selective anti-human immunodeficiency virus type 1 (HIV-1) activity in vivo. EMV showed little or no toxicity towards human mitochondria or human bone marrow progenitor cells. Pharmacokinetics were linear for both rats and monkeys, and oral absorption was 68% in rats. Whole-body autoradiography showed widespread distribution in tissue 30 min after rats were given an oral dose of [(14)C]EMV at 10 mg/kg of body weight. In rats given an oral dose of 250 mg/kg, there were equal levels of EMV in the plasma and the brain. In vitro experiments using liver microsomes demonstrated that the metabolism of EMV by human microsomes is approximately a third of that encountered with rat and monkey microsomes. In 1-month, 3-month, and chronic toxicology experiments (6 months with rats and 1 year with cynomolgus monkeys), toxicity was limited to readily reversible effects on the kidney consisting of vacuolation of kidney tubular epithelial cells and mild increases in blood urea nitrogen. Liver weights increased at the higher doses in rats and monkeys and were attributed to the induction of drug-metabolizing enzymes. EMV tested negative for genotoxic activity, and except for decreased feed consumption at the high dose (160 mg/kg/day), with resultant decreases in maternal and fetal body weights, EMV produced no adverse effects in a complete range of reproductive toxicology experiments performed on rats and rabbits. These results support the clinical development of EMV as a treatment for HIV-1 infection in adult and pediatric patient populations. PMID:10602732

  7. Safety Assessment, In Vitro and In Vivo, and Pharmacokinetics of Emivirine, a Potent and Selective Nonnucleoside Reverse Transcriptase Inhibitor of Human Immunodeficiency Virus Type 1

    PubMed Central

    Szczech, G. M.; Furman, P.; Painter, G. R.; Barry, D. W.; Borroto-Esoda, K.; Grizzle, T. B.; Blum, M. R.; Sommadossi, J.-P.; Endoh, R.; Niwa, T.; Yamamoto, M.; Moxham, C.

    2000-01-01

    Emivirine (EMV), formerly known as MKC-442, is 6-benzyl-1-(ethoxymethyl)-5-isopropyl-uracil, a novel nonnucleoside reverse transcriptase inhibitor that displays potent and selective anti-human immunodeficiency virus type 1 (HIV-1) activity in vivo. EMV showed little or no toxicity towards human mitochondria or human bone marrow progenitor cells. Pharmacokinetics were linear for both rats and monkeys, and oral absorption was 68% in rats. Whole-body autoradiography showed widespread distribution in tissue 30 min after rats were given an oral dose of [14C]EMV at 10 mg/kg of body weight. In rats given an oral dose of 250 mg/kg, there were equal levels of EMV in the plasma and the brain. In vitro experiments using liver microsomes demonstrated that the metabolism of EMV by human microsomes is approximately a third of that encountered with rat and monkey microsomes. In 1-month, 3-month, and chronic toxicology experiments (6 months with rats and 1 year with cynomolgus monkeys), toxicity was limited to readily reversible effects on the kidney consisting of vacuolation of kidney tubular epithelial cells and mild increases in blood urea nitrogen. Liver weights increased at the higher doses in rats and monkeys and were attributed to the induction of drug-metabolizing enzymes. EMV tested negative for genotoxic activity, and except for decreased feed consumption at the high dose (160 mg/kg/day), with resultant decreases in maternal and fetal body weights, EMV produced no adverse effects in a complete range of reproductive toxicology experiments performed on rats and rabbits. These results support the clinical development of EMV as a treatment for HIV-1 infection in adult and pediatric patient populations. PMID:10602732

  8. Thirty years of the human immunodeficiency virus epidemic and beyond

    PubMed Central

    Younai, Fariba S

    2013-01-01

    After more than 30 years of battling a global epidemic, the prospect of eliminating human immunodeficiency virus (HIV) as the most challenging infectious disease of the modern era is within our reach. Major scientific discoveries about the virus responsible for this immunodeficiency disease state, including its pathogenesis, transmission patterns and clinical course, have led to the development of potent antiretroviral drugs that offer great hopes in HIV treatment and prevention. Although these agents and many others still in development and testing are capable of effectively suppressing viral replication and survival, the medical management of HIV infection at the individual and the population levels remains challenging. Timely initiation of antiretroviral drugs, adherence to the appropriate therapeutic regimens, effective use of these agents in the pre and post-exposure prophylaxis contexts, treatment of comorbid conditions and addressing social and psychological factors involved in the care of individuals continue to be important considerations. PMID:24136672

  9. Lymphoid Organs Function as Major Reservoirs for Human Immunodeficiency Virus

    Microsoft Academic Search

    Giuseppe Pantaleo; Cecilia Graziosi; Luca Butini; Philip A. Pizzo; Steven M. Schnittman; Donald P. Kotler; Anthony S. Fauci

    1991-01-01

    The total number of human immunodeficiency virus type 1 (HIV-1)-infected circulating CD4^+ T lymphocytes is considered to be a reflection of the HIV burden at any given time during the course of HIV infection. However, the low frequency of HIV-infected circulating CD4^+ T lymphocytes and the low level or absence of plasma viremia in the early stages of infection do

  10. Endocrinopathies in children infected with human immunodeficiency virus.

    PubMed

    Loomba-Albrecht, Lindsey A; Bregman, Thea; Chantry, Caroline J

    2014-09-01

    Endocrine changes (including adrenal insufficiency, disorders of growth and puberty, thyroid dysfunction, metabolic abnormalities and osteopenia) accompany human immunodeficiency virus (HIV) infection in pediatric patients. The cause of these changes is multifactorial and includes direct viral effects of HIV, and effects of antiretroviral therapy. These effects may be of particular importance in childhood given the critical developmental processes that occur during this time period and the likelihood of prolonged exposure to the virus and medications. PMID:25169569

  11. Suspected primary immunodeficiency syndrome in three related Irish wolfhounds.

    PubMed

    Leisewitz, A L; Spencer, J A; Jacobson, L S; Schroeder, H

    1997-05-01

    Three related Irish wolfhound dogs less than one year old presented with a history of chronic nasal discharge and signs of lower respiratory tract disease. These responded well to treatment initially but were chronically recurring. Cursory evaluation of the immune system (full blood counts, globulin determination and fractionation, electrophoresis and lymphocyte blastogenesis) seemed to indicate a cell-mediated immunodeficiency which, because of the age of the patients, is strongly suspected to be primary. PMID:9179818

  12. Tissue tropism of simian immunodeficiency virus in rhesus monkeys

    SciTech Connect

    Wyand, M.S.

    1989-01-01

    Simian immunodeficiency virus (SIV) is a T-lymphotropic lentivirus that is genetically, immunologically, and morphologically related to the human immunodeficiency viruses type 1 and 2 (HIV-1, HIV-2). In rhesus monkeys, SIV induces a progressively fatal immunodeficiency syndrome strikingly similar to human acquired immunodeficiency syndrome (AIDS). The tissue and cellular tropism of SIV was determined by immunocytochemistry and in situ hybridization using a 3.48 kilobase SIV envelope gene probe labeled with biotin, {sup 35}S, or {sup 3}H. Probes labeled with {sup 35}S nonspecifically bound to tissue eosinophils and produced poor signal resolution compared to tritium labeled probes. Biotin labeled probes did not detect SIV under similar hybridization conditions. Formalin-fixed, paraffin-embedded tissues produced strong hybridization signal with superior morphology compared to frozen tissues. Gastrointestinal, respiratory, and lymphoid tissues most frequently contained SIV RNA. The distribution of SIV did not correlate with sex, or viral inoculum, but was most extensive in animals with SIV induced granulomatous encephalitis. SIV was most frequently observed in lymphocytes and macrophages. In the brain focal granulomas were composed almost entirely of EBM11+, lysozyme+, macrophages which contained large amounts of SIV RNA and p27 core protein detected by the monoclonal antibody R1C7. Cells away from granulomas in the brain parenchyma and around blood vessels contained virus and were compatible with oligodendrocytes and astrocytes. Lymph nodes in follicular hyperplasia contained small numbers of SIV positive cells compatible with lymphocytes in the paracortex and mantle zones as well as in cells of the germinal center. Lymph nodes in various stages of follicular depletion with expanded paracortices contained large numbers of cells with SIV RNA in lymphocytes and macrophages.

  13. [Germinal tumor of the testis and acquired immunodeficiency syndrome].

    PubMed

    Carrasco Canóvas, N; Carles Galcerán, J; Nohales Taurines, G; Arango Toro, O; Cortadellas Angel, R; Bielsa Gali, O; Gelabert Mas, A

    1997-01-01

    Over the last few years a number of testicular tumours in seropositive patients or patients with AIDS-diagnostic factors have been described in the literature with no clear relationship having been established between both conditions. Most authors believe management should not differ from that being given to non-immunodeficient patients. The paper presents one case of non-seminomatous germinal tumour in a 41-year old homosexual patient, HIV positive, with unfavourable evolution in spite of the treatment received. PMID:9494163

  14. The Immunosuppressant Rapamycin Represses Human Immunodeficiency Virus Type 1 Replication

    Microsoft Academic Search

    Jocelyn Roy; Jean-Sebastien Paquette; Jean-Francois Fortin; Michel J. Tremblay

    2002-01-01

    The immunosuppressive macrolide rapamycin is used in humans to prevent graft rejection. This drug acts by selectively repressing the translation of proteins that are encoded by an mRNA bearing a 5-polypyrimidine tract (e.g., ribosomal proteins, elongation factors). The human immunodeficiency virus type 1 (HIV-1) carries a polypyrimidine motif that is located within the tat exon 2. Treatment of human T

  15. Tracking environmental norovirus contamination in a pediatric primary immunodeficiency unit.

    PubMed

    Xerry, Jacqueline; Gallimore, Chris I; Cubitt, David; Gray, Jim J

    2010-07-01

    Norovirus strains were detected in two patients and in environmental swabs from a pediatric primary immunodeficiency unit in London, United Kingdom, during an infection control incident in November and December 2007. Detailed analyses of the gene encoding the P2 domain demonstrated that the majority of the strains were not related to the patients and that the environmental contamination was most likely due to secondary transfer by the hands of staff or visitors. PMID:20444966

  16. Tracking Environmental Norovirus Contamination in a Pediatric Primary Immunodeficiency Unit ?

    PubMed Central

    Xerry, Jacqueline; Gallimore, Chris I.; Cubitt, David; Gray, Jim J.

    2010-01-01

    Norovirus strains were detected in two patients and in environmental swabs from a pediatric primary immunodeficiency unit in London, United Kingdom, during an infection control incident in November and December 2007. Detailed analyses of the gene encoding the P2 domain demonstrated that the majority of the strains were not related to the patients and that the environmental contamination was most likely due to secondary transfer by the hands of staff or visitors. PMID:20444966

  17. Human immunodeficiency virus (HIV) related heart disease: A review

    Microsoft Academic Search

    Mahmoud U. Sani; Basil N. Okeahialam; Sani H. Aliyu; David A. Enoch

    2005-01-01

    Summary Recent advances in the knowledge of human immunodeficiency virus (HIV) replication and transmission as well as the emergence of effective antiretroviral therapies are leading to longer survival times for HIV- infected individuals. As a result, organ-related manifestations of late-stage HIV infection, including HIV-related heart diseases have emerged. It is now clear that cardiac involvement in HIV seropositive patients is

  18. Inhibition of human immunodeficiency virus type-1 integrase by curcumin

    Microsoft Academic Search

    Abhijit Mazumder; Krishnamachari Raghavan; John Weinstein; Kurt W. Kohn; Yves Pommier

    1995-01-01

    Curcumin (diferuloylmethane) is the yellow pigment in turmeric (Curcuma longa L.) that is widely used as a spice, food coloring (curry) and preservative. Curcumin exhibits a variety of pharmacological effects including antitumor, anti-inflammatory, and anti-infectious activities and is currently in clinical trials for AIDS patients. The effects of curcumin have been determined on purified human immunodeficiency virus type 1 (HIV-1)

  19. Human Immunodeficiency Virus: Resistance to Antiretroviral Drugs in Developing Countries

    Microsoft Academic Search

    Rebecca F. Baggaley; Maya L. Petersen; Marcelo A. Soares; Marie-Claude Boily; Francisco I. Bastos

    \\u000a This chapter reviews issues central to understanding the emergence and transmission of drug-resistant human immunodeficiency\\u000a virus (HIV) and its impact on developing countries. We first give an overview of HIV, HIV treatment using antiretroviral drugs,\\u000a and access to treatment in developing countries. Then we review current understanding of the impact of adherence and treatment\\u000a interruption on the emergence of resistance

  20. Neutralization of porcine endogenous retrovirus by antibodies against the membrane-proximal external region of the transmembrane envelope protein.

    PubMed

    Waechter, Alexander; Eschricht, Magdalena; Denner, Joachim

    2013-03-01

    Immunization of different species including goats, rats, hamsters and guinea pigs with the recombinant ectodomain of the transmembrane envelope (TM) protein p15E of porcine endogenous retrovirus (PERV) has been shown to result in the production of virus-neutralizing antibodies. The sera recognize two groups of epitopes, one located in the fusion peptide-proximal region (FPPR) and the second in the membrane-proximal external region (MPER) of p15E. Most interestingly, the epitopes in the MPER are similar to epitopes in the TM protein gp41 of human immunodeficiency virus type 1 (HIV-1) recognized by mAbs 2F5 and 4E10, which broadly neutralize HIV-1. To study which epitope and which antibody population are involved in the process of neutralization of PERV, this study generated a new antiserum in a goat using an elongated ectodomain of p15E. The immune serum neutralized PERV at a higher titre and recognized broader epitopes in the FPPR and MPER of p15E. For the first time, antibody subpopulations were isolated from this serum using affinity chromatography with immobilized proteins and peptides corresponding to the FPPR and MPER of p15E. Only the affinity-purified antibodies specifically binding the MPER neutralized PERV, indicating that, as in the case of HIV-1, the MPER is an important target of neutralizing activity. PMID:23223617

  1. Magnitude and Breadth of the Neutralizing Antibody Response in the RV144 and Vax003 HIV-1 Vaccine Efficacy Trials

    PubMed Central

    Montefiori, David C.; Karnasuta, Chitraporn; Huang, Ying; Ahmed, Hasan; Gilbert, Peter; de Souza, Mark S.; McLinden, Robert; Tovanabutra, Sodsai; Laurence-Chenine, Agnes; Sanders-Buell, Eric; Moody, M. Anthony; Bonsignori, Mattia; Ochsenbauer, Christina; Kappes, John; Tang, Haili; Greene, Kelli; Gao, Hongmei; LaBranche, Celia C.; Andrews, Charla; Polonis, Victoria R.; Rerks-Ngarm, Supachai; Pitisuttithum, Punnee; Nitayaphan, Sorachai; Kaewkungwal, Jaranit; Self, Steve G.; Berman, Phillip W.; Francis, Donald; Sinangil, Faruk; Lee, Carter; Tartaglia, Jim; Robb, Merlin L.; Haynes, Barton F.; Michael, Nelson L.; Kim, Jerome H.

    2012-01-01

    Background.?A recombinant canarypox vector expressing human immunodeficiency virus type 1 (HIV-1) Gag, Pro, and membrane-linked gp120 (vCP1521), combined with a bivalent gp120 protein boost (AIDSVAX B/E), provided modest protection against HIV-1 infection in a community-based population in Thailand (RV144 trial). No protection was observed in Thai injection drug users who received AIDSVAX B/E alone (Vax003 trial). We compared the neutralizing antibody response in these 2 trials. Methods.?Neutralization was assessed with tier 1 and tier 2 strains of virus in TZM-bl and A3R5 cells. Results.?Neutralization of several tier 1 viruses was detected in both RV144 and Vax003. Peak titers were higher in Vax003 and waned rapidly in both trials. The response in RV144 was targeted in part to V3 of gp120.vCP1521 priming plus 2 boosts with gp120 protein was superior to 2 gp120 protein inoculations alone, confirming a priming effect for vCP1521. Sporadic weak neutralization of tier 2 viruses was detected only in Vax003 and A3R5 cells. Conclusion.?The results suggest either that weak neutralizing antibody responses can be partially protective against HIV-1 in low-risk heterosexual populations or that the modest efficacy seen in RV144 was mediated by other immune responses, either alone or in combination with neutralizing antibodies. PMID:22634875

  2. Immunodeficiency due to mutations in ORAI1 and STIM1

    PubMed Central

    Feske, Stefan; Picard, Capucine; Fischer, Alain

    2010-01-01

    Lymphocyte activation requires Ca2+ influx through specialized Ca2+ channels in the plasma membrane. In T cells the predominant Ca2+ channel is the Ca2+ release activated Ca2+ (CRAC) channel encoded by the gene ORAI1. ORAI1 is activated by stromal interaction molecule (STIM) 1 that is localized in the ER where it senses the concentration of stored Ca2+. Following antigen binding to immunoreceptors such as the TCR, ER Ca2+ stores are depleted, STIM1 is activated and ORAI1-CRAC channels open resulting in what is referred to as store-operated Ca2+ entry (SOCE). Mutations in ORAI1 and STIM1 genes in human patients that lead to expression of non-functional ORAI1 or complete lack of ORAI1 or STIM1 protein are associated with a unique clinical phenotype that is characterized by immunodeficiency, muscular hypotonia and anhydrotic ectodermal dysplasia, as well as, in the case of STIM1 deficiency, autoimmunity and lymphoproliferative disease. The immunodeficiency in these patients is due to a severe defect in T cell activation but not in lymphocyte development. This review describes the immunological and non-immunological phenotypes of patients with defects in SOCE and CRAC channel function and discusses them in the context of similar immunodeficiency diseases and animal models of ORAI1 and STIM1 function. PMID:20189884

  3. Neutral ISM surrounding starburst regions

    NASA Astrophysics Data System (ADS)

    Lebouteiller, V.; Kunth, D.; Lequeux, J.; Aloisi, A.; Désert, J.-D.; Lecavelier Des Etangs, A.; Hébrard, G.; Vidal-Madjar, A.

    2005-05-01

    The Far Ultraviolet Spectroscopic Explorer (FUSE) offers the possibility to study the extragalactic interstellar medium (ISM) in sightlines toward UV-bright H II regions where stars are forming. From the absorption lines of species such as H I, O I, N I, Ar I, or Fe II we are able to derive the chemical composition of the diffuse neutral gas and compare it to the H II region composition. A major aim is to know whether H II regions truly reflect the ISM abundances of a galaxy or whether these regions are self-polluted with metals ejected by massive stars during the present starburst episode. Five Blue Compact Dwarfs galaxies (BCDs) have been investigated so far. The situation remains, however, still unclear. For instance, the oxygen abundance is either the same within the neutral and ionized ISM (in I Zw 18, I Zw 36 and SBS 0335-052) or 10 × lower in the neutral ISM (in Markarian 59). It seems, however, that nitrogen (using N I as a tracer in the neutral gas) and argon (using Ar I) are systematically lower in the neutral phase. Conscious of the uncertainties due to the complexity of the sightlines and the ionization structure, we have obtained high-quality spectra of individual H II regions in spiral galaxies. There, the situation is much easier to understand, allowing us to model H II regions with photoionization models. This study on NGC 604 provides a test on the method used for the BCDs. In NGC 604, we find a global underabundance in the neutral gas of N, O, Ar, and Fe as compared to the ionized gas, suggesting the presence of primordial gas in the line of sight. Furthermore, it appears that N I and Ar I are good tracers, respectively of nitrogen and argon, in the diffuse neutral gas surrounding NGC 604.

  4. Behavioral and neurophysiological hallmarks of simian immunodeficiency virus infection in macaque monkeys

    Microsoft Academic Search

    P. D. Cheney; M. Riazi; J. M. Marcario

    2008-01-01

    Macaque monkeys infected with various neurovirulent forms of simian immunodeficiency virus (SIV) represent highly effective\\u000a models, not only of systemic acquired immunodeficiency virus (AIDS), but also neuroAIDS. Behavioral studies with this model\\u000a have clearly established that SIV-infected monkeys show both cognitive and motor impairments resembling those that have been\\u000a reported in human immunodeficiency virus (HIV)-infected humans. This paper combines data

  5. Successful allogeneic hemopoietic stem cell transplantation in a child who had anhidrotic ectodermal dysplasia with immunodeficiency.

    PubMed

    Dupuis-Girod, Sophie; Cancrini, Caterina; Le Deist, Françoise; Palma, Paolo; Bodemer, Christine; Puel, Anne; Livadiotti, Susanna; Picard, Capucine; Bossuyt, Xavier; Rossi, Paolo; Fischer, Alain; Casanova, Jean-Laurent

    2006-07-01

    Anhidrotic ectodermal dysplasia with immunodeficiency is associated with multiple infections and a poor clinical outcome. Hypomorphic mutations in nuclear factor kappaB essential modulator (NEMO)/IkappaB kinase complex and a hypermorphic mutation in inhibitor alpha of nuclear factor kappaB (IkappaBalpha) both result in impaired nuclear factor kappaB activation and are associated with X-recessive and autosomal-dominant forms of anhidrotic ectodermal dysplasia with immunodeficiency, respectively. Autosomal-dominant anhidrotic ectodermal dysplasia with immunodeficiency is also associated with a severe T-cell phenotype. It is not known whether hematopoietic stem cell transplantation can cure immune deficiency in children with anhidrotic ectodermal dysplasia with immunodeficiency. A boy with autosomal-dominant anhidrotic ectodermal dysplasia with immunodeficiency and a severe T-cell immunodeficiency underwent transplantation at 1 year of age with haploidentical T-cell-depleted bone marrow after myeloablative conditioning. Engraftment occurred, with full hematopoietic chimerism. Seven years after transplantation, clinical outcome is favorable, with normal T-cell development. As expected, the developmental features of the anhidrotic ectodermal dysplasia syndrome have appeared and persisted. This is the first report of successful hematopoietic stem cell transplantation in a child with anhidrotic ectodermal dysplasia with immunodeficiency. Hematopoietic stem cell transplantation is well tolerated and efficiently cures the profound immunodeficiency associated with autosomal-dominant anhidrotic ectodermal dysplasia with immunodeficiency. PMID:16769798

  6. In Vivo Distribution of the Human Immunodeficiency Virus\\/Simian Immunodeficiency Virus Coreceptors: CXCR4, CCR3, and CCR5

    Microsoft Academic Search

    LINQI ZHANG; TIAN HE; ANDREW TALAL; GLORIA WANG; SARAH S. FRANKEL

    We have evaluated the in vivo distribution of the major human immunodeficiency virus\\/simian immunode- ficiency virus (HIV\\/SIV) coreceptors, CXCR4, CCR3, and CCR5, in both rhesus macaques and humans. T lymphocytes and macrophages in both lymphoid and nonlymphoid tissues are the major cell populations expressing HIV\\/SIV coreceptors, reaffirming that these cells are the major targets of HIV\\/SIV infection in vivo. In

  7. Local connectivity of neutral networks.

    PubMed

    Reidys, Christian M

    2009-02-01

    This paper studies local connectivity of neutral networks of RNA secondary and pseudoknot structures. A neutral network denotes the set of RNA sequences that fold into a particular structure. It is called locally connected, if in the limit of long sequences, the distance of any two of its sequences scales with their distance in the n-cube. One main result of this paper is that lambda(n) = n(-1/2+Delta) is the threshold probability for local connectivity for neutral networks, considered as random subgraphs of n-cubes. Furthermore, we analyze local connectivity for finite sequence length and different alphabets. We show that it is closely related to the existence of specific paths within the neutral network. We put our theoretical results into context with folding algorithms into minimum-free energy RNA secondary and pseudoknot structures. Finally, we relate our structural findings with dynamics by discussing the role of local connectivity in the context of neutral evolution. PMID:19115073

  8. Broadly neutralizing antibody VRC01 prevents HIV-1 transmission from plasmacytoid dendritic cells to CD4 T lymphocytes.

    PubMed

    Su, Bin; Lederle, Alexandre; Laumond, Géraldine; Ducloy, Camille; Schmidt, Sylvie; Decoville, Thomas; Moog, Christiane

    2014-09-01

    Plasmacytoid dendritic cells (pDC) poorly replicate human immunodeficiency virus type 1 (HIV-1) but efficiently transfer HIV-1 to adjacent CD4 T lymphocytes. We found that coculture with T lymphocytes downregulates SAMHD1 expression, enhances HIV-1 replication, and increases pDC maturation and alpha interferon (IFN-?) secretion. HIV-1 transfer to T lymphocytes is inhibited by broadly neutralizing antibody VRC01 with efficiency similar to that of cell-free infection of T lymphocytes. Interestingly, prevention of HIV-1 transmission by VRC01 retains IFN-? secretion. These results emphasize the multiple functions of VRC01 in protection against HIV-1 acquisition. PMID:24965460

  9. Mode of action of SDZ NIM 811, a nonimmunosuppressive cyclosporin A analog with activity against human immunodeficiency virus (HIV) type 1: interference with HIV protein-cyclophilin A interactions.

    PubMed Central

    Billich, A; Hammerschmid, F; Peichl, P; Wenger, R; Zenke, G; Quesniaux, V; Rosenwirth, B

    1995-01-01

    Cyclosporins, in particular the nonimmunosuppressive derivative SDZ NIM 811, exhibit potent anti-human immunodeficiency virus type 1 (HIV-1) activity in vitro. SDZ NIM 811 interferes at two stages of the viral replication cycle: (i) translocation of the preintegration complex to the nucleus and (ii) production of infectious virus particles. Immunosuppressive activity is not correlated with anti-HIV-1 activity of cyclosporins. However, binding to cyclophilin A, the major cellular receptor protein of cyclosporins, is a prerequisite for HIV inhibition: all structural changes of the cyclosporin A molecule leading to loss of affinity to cyclophilin abolished the antiviral effect. Cyclosporin derivatives did not interact directly with HIV-1 proteins; cyclophilin was the only detectable receptor protein for antivirally active cyclosporins. There is no evidence that inhibition of HIV occurs via a gain of function of cyclophilin in the presence of cyclosporins: the complex of cyclophilin A with SDZ NIM 811 does not bind to calcineurin or to any other viral or cellular proteins under conditions in which calcineurin binding to the cyclophilin A-cyclosporin A complex is easily detectable. Thus, the loss of function caused by binding of cyclosporins to cyclophilin seems to be sufficient for the anti-HIV effect. Cyclophilin A was demonstrated to bind to HIV-1 p24gag, and the formation of complexes was blocked by cyclosporins with 50% inhibitory concentrations of about 0.7 microM. HIV-2 and simian immunodeficiency virus are only weakly or not at all inhibited by cyclosporins. For gag-encoded proteins derived from HIV-1, HIV-2, or simian immunodeficiency virus particles, cyclophilin-binding capacity correlated with sensitivity of the viruses to inhibition by cyclosporins. Cyclophilin A also binds to HIV-1 proteins other than gag-encoded proteins, namely, p17gag, Nef, Vif, and gp120env; the biological significance of these interactions is questionable. We conclude that HIV-1 Gag-cyclophilin A interaction may be essential in HIV-1 replication, and interference with this interaction may be the molecular basis for the antiviral activity of cyclosporins. PMID:7884893

  10. Heterologous Envelope Immunogens Contribute to AIDS Vaccine Protection in Rhesus Monkeys

    Microsoft Academic Search

    Norman L. Letvin; Yue Huang; Bimal K. Chakrabarti; Ling Xu; Michael S. Seaman; Kristin Beaudry; Birgit Korioth-Schmitz; Faye Yu; Daniela Rohne; Kristi L. Martin; Ayako Miura; Wing-Pui Kong; Zhi-Yong Yang; Rebecca S. Gelman; Olga G. Golubeva; David C. Montefiori; John R. Mascola; Gary J. Nabel

    2004-01-01

    Because a strategy to elicit broadly neutralizing anti-human immunodeficiency virus type 1 (HIV-1) anti- bodies has not yet been found, the role of an Env immunogen in HIV-1 vaccine candidates remains undefined. We sought to determine whether an HIV-1 Env immunogen genetically disparate from the Env of the challenge virus can contribute to protective immunity. We vaccinated Indian-origin rhesus monkeys

  11. Solids formation on filtrate neutralization

    Microsoft Academic Search

    1988-01-01

    The Separations Technology Laboratory was requested to study what happens when a filtrate solution, which will be a F B-Line product, is neutralized with sodium hydroxide. The primary concern was the formation of solids that could cause damage in pump seals, resulting in their failure. The results of these experiments indicate that under process conditions, granular, crystalline sodium fluoride will

  12. Self-neutralized ion beam

    SciTech Connect

    Salvadori, M. C.; Teixeira, F. S. [Institute of Physics, University of Sao Paulo, C.P. 66318, CEP 05315-970 Sao Paulo S.P. (Brazil); Nikolaev, A.; Savkin, K. P.; Oks, E. M. [High Current Electronics Institute, Russian Academy of Sciences, Tomsk 634055 (Russian Federation); Spaedtke, P. [Gesellschaft fuer Schwerionenforschung, D-64291 Darmstadt (Germany); Yu, K. M.; Brown, I. G. [Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States)

    2011-10-15

    A vacuum arc ion source provides high current beams of metal ions that have been used both for accelerator injection and for ion implantation, and in both of these applications the degree of space charge neutralization of the beam is important. In accelerator injection application, the beam from the ion source may be accelerated further (post-acceleration), redirected by a bending magnet(s), or focused with magnetic or electrostatic lenses, and knowledge of the beam space charge is needed for optimal design of the optical elements. In ion implantation application, any build-up of positive charge in the insulating targets must be compensated by a simultaneous flux of cold electrons so as to provide overall charge neutrality of the target. We show that in line-of-sight ion implantation using a vacuum arc ion source, the high current ion beam carries along its own background sea of cold electrons, and this copious source of electrons provides a ''self-neutralizing'' feature to the beam. Here we describe experiments carried out in order to demonstrate this effect, and we provide an analysis showing that the beam is space-charge-neutralized to a very high degree.

  13. MSFC Skylab neutral buoyancy simulator

    NASA Technical Reports Server (NTRS)

    1974-01-01

    The use of a neutral buoyancy simulator for developing extravehicular activity systems and for training astronauts in weightless activities is discussed. The construction of the facility and the operations are described. The types of tests and the training activities conducted in the simulator are reported. Photographs of the components of the simulator and actual training exercises are included.

  14. Low energy neutral atom imaging

    SciTech Connect

    McComas, D.J.; Funsten, H.O.; Gosling, J.T.; Moore, K.R.; Thomsen, M.F.

    1992-01-01

    Energetic neutral atom (ENA) and low energy neutral atom (LENA) imaging of space plasmas are emerging new technology which promises to revolutionize the way we view and understand large scale space plasma phenomena and dynamics. ENAs and LENAs are produced in the magnetosphere by charge exchange between energetic and plasma ions and cold geocoronal neutrals. While imaging techniques have been previously developed for observing ENAs, with energies above several tens of keV, most of the ions found in the terrestrial magnetosphere have lower energies. We recently suggested that LENAs could be imaged by first converting the neutrals to ions and then electrostatically analyzing them to reject the UV background. In this paper we extend this work to examine in detail the sensor elements needed to make an LENA imager. These elements are (1) a biased collimator to remove the ambient plasma ions and electrons and set the azimuthal field-of-view; (2) a charge modifier to convert a portion of the incident LENAs to ions; (3) an electrostatic analyzer to reject UV light and set the energy passband; and (4) a coincidence detector to measure converted LENAs while rejecting noise and penetrating radiation. We also examine the issue of LENA imager sensitivity and describe ways of optimizing sensitivity in the various sensor components. Finally, we demonstrate in detail how these general considerations are implemented by describing one relatively straightforward design based on a hemispherical electrostatic analyzer.

  15. Low energy neutral atom imaging

    SciTech Connect

    McComas, D.J.; Funsten, H.O.; Gosling, J.T.; Moore, K.R.; Thomsen, M.F.

    1992-05-01

    Energetic neutral atom (ENA) and low energy neutral atom (LENA) imaging of space plasmas are emerging new technology which promises to revolutionize the way we view and understand large scale space plasma phenomena and dynamics. ENAs and LENAs are produced in the magnetosphere by charge exchange between energetic and plasma ions and cold geocoronal neutrals. While imaging techniques have been previously developed for observing ENAs, with energies above several tens of keV, most of the ions found in the terrestrial magnetosphere have lower energies. We recently suggested that LENAs could be imaged by first converting the neutrals to ions and then electrostatically analyzing them to reject the UV background. In this paper we extend this work to examine in detail the sensor elements needed to make an LENA imager. These elements are (1) a biased collimator to remove the ambient plasma ions and electrons and set the azimuthal field-of-view; (2) a charge modifier to convert a portion of the incident LENAs to ions; (3) an electrostatic analyzer to reject UV light and set the energy passband; and (4) a coincidence detector to measure converted LENAs while rejecting noise and penetrating radiation. We also examine the issue of LENA imager sensitivity and describe ways of optimizing sensitivity in the various sensor components. Finally, we demonstrate in detail how these general considerations are implemented by describing one relatively straightforward design based on a hemispherical electrostatic analyzer.

  16. A protocol for routine voluntary antepartum human immunodeficiency virus antibody screening.

    PubMed

    Lindsay, M K

    1993-02-01

    Human immunodeficiency virus infection among both women of reproductive age and their infants is rapidly increasing. One strategy to address this increase involves the offering of routine voluntary antepartum human immunodeficiency virus antibody counseling and testing. The rationale for this policy is that all prenatal patients are educated about the major modes of viral transmission and encouraged to practice risk reduction behavior. Human immunodeficiency virus-infected women receive comprehensive prenatal care; they are referred for medical follow-up, and their infants are identified and targeted for pediatric infectious disease follow-up. During the past 4 years we have developed a protocol for antepartum human immunodeficiency virus screening in our institution. The protocol includes a self-reported human immunodeficiency virus risk behavior profile, pretest counseling conducted by trained human immunodeficiency virus counselors in small groups, written informed consent for human immunodeficiency virus antibody testing, posttest counseling, and education. By following this protocol we have identified and referred for follow-up > 350 human immunodeficiency virus-infected women. PMID:8438912

  17. AIDS . Author manuscript Non-AIDS-defining deaths and immunodeficiency in the era of combination

    E-print Network

    Paris-Sud XI, Université de

    AIDS . Author manuscript Page /1 12 Non-AIDS-defining deaths and immunodeficiency in the era immunodeficiency is associated with the most frequent non-AIDS-defining causes of death, in the era of combination (71,230 person-years follow-up), 597 died, 333 (55.7 ) from non-AIDS-defining causes. Non-AIDS

  18. Human Immunodeficiency Virus-Type 1 (HIV-1) and the Brain.

    ERIC Educational Resources Information Center

    Grant, Igor; Heaton, Robert K.

    1990-01-01

    Provides update on what is currently known about neurobehavioral correlates of infection with human immunodeficiency virus-Type 1 (HIV-1), causative agent of acquired immunodeficiency syndrome. Discusses methodological and theoretical issues complicating interpretation of existing data and suggests strategies for future research in this area. (NB)

  19. Simian Immunodeficiency Virus Rapidly Penetrates the Cervicovaginal Mucosa after Intravaginal Inoculation and Infects Intraepithelial Dendritic Cells

    Microsoft Academic Search

    JINJIE HU; MURRAY B. GARDNER; CHRISTOPHER J. MILLER

    2000-01-01

    Despite recent insights into mucosal human immunodeficiency virus (HIV) transmission, the route used by primate lentiviruses to traverse the stratified squamous epithelium of mucosal surfaces remains undefined. To determine if dendritic cells (DC) are used by primate lentiviruses to traverse the epithelial barrier of the genital tract, rhesus macaques were intravaginally exposed to cell-free simian immunodeficiency virus SIVmac251. We examined

  20. Body Composition and Endocrine Function in Women with Acquired Immunodeficiency Syndrome Wasting

    Microsoft Academic Search

    STEVEN GRINSPOON; COLLEEN CORCORAN; KAREN MILLER; BEVERLY M. K. BILLER; HASAN ASKARI; EMILY WANG; JANE HUBBARD; ELLEN J. ANDERSON; NESLI BASGOZ; HOWARD M. HELLER; ANNE KLIBANSKI

    2010-01-01

    The acquired immunodeficiency syndrome (AIDS) wasting syn- drome is a devastating complication of human immunodeficiency virus (HIV) infection characterized by progressive weight loss and severe inanition. In men, the wasting syndrome is characterized by a disproportionate decrease in lean body mass and relative fat spar- ing. In contrast, relatively little is known about the gender-specific changes in body composition that

  1. Risk of Vision Loss in Patients With Cytomegalovirus RetinitisandtheAcquiredImmunodeficiencySyndrome

    Microsoft Academic Search

    John H. Kempen; Douglas A. Jabs; Laura A. Wilson; James P. Dunn; Sheila K. West; James A. Tonascia

    Objective: To characterize the effect of cytomegalovi- rus (CMV) retinitis and its treatment on visual acuity in patients with the acquired immunodeficiency syn- drome. Methods: We evaluated 648 consecutive patients with the acquired immunodeficiency syndrome at 1 center for the prevalence of visual impairment at the time of CMV retinitis diagnosis and for the incidence of visual impair- ment across

  2. Increased titers of neutralizing antibodies after immunization with both envelope proteins of the porcine endogenous retroviruses (PERVs).

    PubMed

    Denner, Joachim; Mihica, Debora; Kaulitz, Danny; Schmidt, Christa-Maria

    2012-01-01

    Despite enormous difficulties to induce antibodies neutralizing HIV-1, especially broadly neutralizing antibodies directed against the conserved membrane proximal external region (MPER) of the transmembrane envelope protein, such antibodies can be easily induced in the case of gammaretroviruses, among them the porcine endogenous retroviruses (PERVs). In addition to neutralizing antibodies directed against the transmembrane envelope protein p15E, neutralizing antibodies were also induced by immunization with the surface envelope protein gp70. PERVs represent a special risk for xenotransplantation using pig tissues or organs since they are integrated in the genome of all pigs and infect human cells and a vaccine may protect from transmission to the recipient. To investigate the effect of simultaneous immunization with both proteins in detail, a study was performed in hamsters. Gp70 and p15E of PERV were produced in E. coli, purified and used for immunization. All animals developed binding antibodies against the antigens used for immunization. Sera from animals immunized with p15E recognized epitopes in the MPER and the fusion peptide proximal region (FPPR) of p15E. One MPER epitope showed a sequence homology to an epitope in the MPER of gp41 of HIV-1 recognized by broadly neutralizing antibodies found in HIV infected individuals. Neutralizing antibodies were detected in all sera. Most importantly, sera from animals immunized with gp70 had a higher neutralizing activity when compared with the sera from animals immunized with p15E and sera from animals immunized with gp70 together with p15E had a higher neutralizing activity compared with sera from animals immunized with each antigen alone. These immunization studies are important for the development of vaccines against other retroviruses including the human immunodeficiency virus HIV-1. PMID:23126255

  3. Chronic Alcohol Accentuates Simian Acquired Immunodeficiency Syndrome-Associated Wasting

    PubMed Central

    Molina, Patricia E.; Lang, Charles H.; McNurlan, Margaret; Bagby, Gregory J.; Nelson, Steve

    2011-01-01

    Background Survival following human immunodeficiency virus (HIV) infection has improved significantly following the advent of highly active antiretroviral therapy. A large percentage of HIV-infected patients consume and abuse alcohol. Erosion of lean body mass is an important contributing factor to patient morbidity and mortality, and is a common feature of both chronic alcohol (ALC) consumption and acquired immunodeficiency syndrome (AIDS). We hypothesized that alcohol-induced loss in lean body mass is likely to exacerbate the AIDS wasting syndrome, particularly at the terminal stage of AIDS (SAIDS). Methods This study examined the impact of chronic, intra-gastric ALC (5 h/d × 4 d/wk; blood alcohol levels = 55 mM to 60 mM) administration on body composition and muscle mass in simian immunodeficiency virus (SIV)-infected male Rhesus macaques in contrast to SIV-infected isocaloric (22 kcal/kg/d) sucrose (SUC)-infused control animals at the terminal stage of SIV infection. Results At terminal stage, ALC/SIV+ animals had significantly lower body weight, body mass index, and limb muscle area than SUC/SIV+ animals. Both ALC/SIV+ and SUC/SIV+ animals had suppressed expression of insulin-like growth factor-I and increased expression of the ubiquitin ligase muscle-specific RING finger-1 mRNA. ALC increased mRNA expression of atrogin- 1 (pre-SIV and at SAIDS) and tumor necrosis factor (TNF)-? (SAIDS). These changes were not associated with significant differences in fractional rates of muscle protein synthesis or in overall survival rate. These data show that chronic ALC exacerbated the loss of muscle mass at terminal SAIDS. Conclusion Our findings suggest the involvement of TNF-? and increased muscle proteolysis via atrogin-1 for the greater erosion of lean body mass at terminal SAIDS in ALC-treated Rhesus macaques. PMID:18028526

  4. Rapid escape from preserved cross-reactive neutralizing humoral immunity without loss of viral fitness in HIV-1-infected progressors and long-term nonprogressors.

    PubMed

    van Gils, Marit J; Bunnik, Evelien M; Burger, Judith A; Jacob, Yodit; Schweighardt, Becky; Wrin, Terri; Schuitemaker, Hanneke

    2010-04-01

    A substantial proportion of human immunodeficiency virus type 1 (HIV-1)-infected individuals has cross-reactive neutralizing activity in serum, with a similar prevalence in progressors and long-term nonprogressors (LTNP). We studied whether disease progression in the face of cross-reactive neutralizing serum activity is due to fading neutralizing humoral immunity over time or to viral escape. In three LTNP and three progressors, high-titer cross-reactive HIV-1-specific neutralizing activity in serum against a multiclade pseudovirus panel was preserved during the entire clinical course of infection, even after AIDS diagnosis in progressors. However, while early HIV-1 variants from all six individuals could be neutralized by autologous serum, the autologous neutralizing activity declined during chronic infection. This could be attributed to viral escape and the apparent inability of the host to elicit neutralizing antibodies to the newly emerging viral escape variants. Escape from autologous neutralizing activity was not associated with a reduction in the viral replication rate in vitro. Escape from autologous serum with cross-reactive neutralizing activity coincided with an increase in the length of the variable loops and in the number of potential N-linked glycosylation sites in the viral envelope. Positive selection pressure was observed in the variable regions in envelope, suggesting that, at least in these individuals, these regions are targeted by humoral immunity with cross-reactive potential. Our results may imply that the ability of HIV-1 to rapidly escape cross-reactive autologous neutralizing antibody responses without the loss of viral fitness is the underlying explanation for the absent effect of potent cross-reactive neutralizing humoral immunity on the clinical course of infection. PMID:20071586

  5. Immediate-early gene region of human cytomegalovirus trans-activates the promoter of human immunodeficiency virus

    Microsoft Academic Search

    M. G. Davis; S. C. Kenney; J. Kamine; J. S. Pagano; E. S. Huang

    1987-01-01

    Almost all homosexual patients with acquired immunodeficiency syndrome are also actively infected with human cytomegalovirus (HCMV). The authors have hypothesized that an interaction between HCMV and human immunodeficiency virus (HIV), the agent that causes acquired immunodeficiency syndrome, may exist at a molecular level and contribute to the manifestations of HIV infection. In this report, they demonstrate that the immediate-early gene

  6. Immediate-Early Gene Region of Human Cytomegalovirus Trans-Activates the Promoter of Human Immunodeficiency Virus

    Microsoft Academic Search

    Michelle G. Davis; Shannon C. Kenney; James Kamine; Joseph S. Pagano; Eng-Shang Huang

    1987-01-01

    Almost all homosexual patients with acquired immunodeficiency syndrome are also actively infected with human cytomegalovirus (HCMV). We have hypothesized that an interaction between HCMV and human immunodeficiency virus (HIV), the agent that causes acquired immunodeficiency syndrome, may exist at a molecular level and contribute to the manifestations of HIV infection. In this report, we demonstrate that the immediate-early gene region

  7. 70 FR 43439 - Draft Guidance for Industry on Nucleic Acid Testing for Human Immunodeficiency Virus Type 1 and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2005-07-27

    ...Human Immunodeficiency Virus Type 1 and Hepatitis C Virus: Testing, Product Disposition...Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis C Virus (HCV): Testing, Product Disposition...Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis C Virus (HCV): Testing, Product...

  8. Oral lesions associated with human immunodeficiency virus disease.

    PubMed

    Patton, Lauren L

    2013-10-01

    Human immunodeficiency virus (HIV)-associated oral disease among people living with HIV infection includes oral candidiasis, oral hairy leukoplakia, Kaposi sarcoma, oral warts, herpes simplex virus ulcers, major aphthous ulcers or ulcers not otherwise specified, HIV salivary gland disease, and atypical gingival and periodontal diseases. Diagnosis of some oral lesions is based on clinical appearance and behavior, whereas others require biopsy, culture, or imaging for definitive diagnosis. Management strategies including pharmacologic and nonpharmacologic approaches are discussed in this article. Dentists also need to be cognizant of the potential oral side effects of HIV antiretroviral medications. PMID:24034072

  9. Alteration in pancreatic islet function in human immunodeficiency virus.

    PubMed

    Haugaard, Steen B

    2014-09-01

    Molecular mechanisms behind the defects in insulin production and secretion associated with antihuman immunodeficiency virus (anti-HIV) therapy and the development of HIV-associated lipodystrophy syndrome (HALS) are discussed in this article. Data suggesting insulin resistance on the beta cell and defects in first-phase insulin release of HALS patients are presented. Hepatic extraction of insulin, nonglucose insulin secretagogues and insulin-like growth factor release may exert influence on the demand of circulating insulin and on insulin secretion in HIV-infected patients. Finally, the paucity in understanding the incretin effects in HIV and HIV therapy in relation to insulin secretion is highlighted. PMID:25169562

  10. Immunodeficiency: updating the personalized medicine approach to diagnostics and therapeutics.

    PubMed

    Buckland, Matthew

    2012-03-01

    The 2011 UK Primary Immunodeficiency Network Forum was held in the Liverpool Arena and Conference Centre. Over 200 healthcare scientists, nurses and doctors were in attendance to discuss a range of issues relating to primary immune deficiencies. This year the biennial forum saw both national and international speakers and a broad representation of posters and oral abstracts from across the interest groups. This article summarizes the keynote lectures and output from 2 days including more than 70 poster presentations and 25 oral presentations. PMID:22390485

  11. Human immunodeficiency virus-associated obstructive lung diseases.

    PubMed

    Gingo, Matthew R; Morris, Alison; Crothers, Kristina

    2013-06-01

    In the era of effective antiretroviral therapy (ART), epidemiologic studies have found that persons infected with human immunodeficiency virus (HIV) have a higher prevalence and incidence of chronic obstructive pulmonary disease than HIV-uninfected persons. In comparison with HIV-uninfected persons and those with well-controlled HIV disease, HIV-infected persons with poor viral control or lower CD4 cell count have more airflow obstruction, a greater decline in lung function, and possibly more severe diffusing impairment. This article reviews the evidence linking HIV infection to obstructive lung disease, and discusses management issues related to the treatment of obstructive lung disease in HIV-infected patients. PMID:23702176

  12. Future directions: lung aging, inflammation, and human immunodeficiency virus.

    PubMed

    Fitzpatrick, Meghan; Crothers, Kristina; Morris, Alison

    2013-06-01

    Chronic lung diseases, including chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH), are unusually prevalent among persons infected with human immunodeficiency virus (HIV). Often these disease states are identified at younger ages than would be expected in the general population. Recent epidemiologic, basic scientific, and cross-sectional clinical data have implicated immune dysfunction and cellular senescence as potential drivers of advanced presentations of age-related diseases in HIV-infected persons. This article describes how HIV-associated COPD and PH may fit into a paradigm of immunosenescence, and outlines the hypothesized associations among chronic HIV infection, immune dysfunction and senescence, and cardiopulmonary outcomes. PMID:23702180

  13. Towards detecting the human immunodeficiency virus using microcantilever sensors

    NASA Astrophysics Data System (ADS)

    Alodhayb, Abdullah; Brown, Nicole; Saydur Rahman, S. M.; Harrigan, Richard; Beaulieu, L. Y.

    2013-04-01

    Detecting the human immunodeficiency virus (HIV) is difficult because the virus is prone to mutations and is in low concentrations in the body. Inside the HIV virion are two well characterized single stranded (ss) RNA molecules (viral genome) that feature both variable regions and regions that are conserved under virus mutation. In this work, microcantilever sensors have been employed as potential HIV detectors by targeting a conserved sequence of the viral genome by attempting to detect target ssDNA and ssRNA molecules that are significantly longer than the ssDNA molecules functionalized on the cantilever.

  14. Human Immunodeficiency Virus gag and protease: partners in resistance

    E-print Network

    Fun, Axel; Wensing, Annemarie MJ; Verheyen, Jens; Nijhuis, Monique

    2012-08-06

    in resi Axel Fun1, Annemarie MJ Wensing1, Jens Verheyen2 and Abstract Human Immunodeficiency Virus (HIV) maturation plays an generation of mature infectious virus particles through pr proteins. An impaired polyprotein processing results in th Consequently... or enhance the rate of cleavage by the viral protease. J Virol 2002, 76:10226–10233. 9. Maguire MF, Guinea R, Griffin P, Macmanus S, Elston RC, Wolfram J, Richards N, Hanlon MH, Porter DJ, Wrin T, Parkin N, Tisdale M, Furfine E, Petropoulos C, Snowden BW...

  15. The Human Immunodeficiency Virus: Infectivity and Mechanisms of Pathogenesis

    NASA Astrophysics Data System (ADS)

    Fauci, Anthony S.

    1988-02-01

    Infection with the human immunodeficiency virus (HIV) results in a profound immunosuppression due predominantly to a selective depletion of helper/inducer T lymphocytes that express the receptor for the virus (the CD4 molecule). HIV also has tropism for the brain leading to neuropsychiatric abnormalities. Besides inducing cell death, HIV can interfere with T4 cell function by various mechanisms. The monocyte serves as a reservoir for HIV and is relatively refractory to its cytopathic effects. HIV can exist in a latent or chronic form which can be converted to a productive infection by a variety of inductive signals.

  16. Rosette formation with mouse erythrocytes. III. Studies in patients with primary immunodeficiency and lymphoproliferative disorders.

    PubMed Central

    Gupta, S; Good, R A; Siegal, F P

    1976-01-01

    Rosette formation with mouse erythrocytes and other cell-surface markers were examined on lymphocytes from patients with a variety of primary immunodeficiency and lymphoproliferative disorders. Mouse erythrocyte rosette-forming cells and lymphocytes with surface immunoglobulins were regularly absent in patients with Bruton type agammaglobulinaemia, immunodeficiency and thymoma syndrome and severe combined immunodeficiency disease. However, they were present in normal or low numbers in patients with common variable immunodeficiency, selective IgA deficiency and ataxis telangiectasia. Lymphocytes from patients with acute lymphoblastic leukaemia Sezary syndrome and mycosis fungoides made no or few rosettes with mouse erythrocytes. Increased numbers of mouse erythrocyte rosette-forming cells were present in patients with chronic lymphocytic leukaemia and Waldenstrom's macroglobulinaemia. The significance of the mouse erythrocyte rosette as a B-cell marker in the analysis of primary immunodeficiency and lymphoproliferative disorders is discussed. PMID:1068759

  17. Development of Broadly Neutralizing Antibodies from Autologous Neutralizing Antibody Responses

    PubMed Central

    Derdeyn, Cynthia A.; Moore, Penny L.; Morris, Lynn

    2014-01-01

    Purpose of Review Detailed genetic and structural characterization has revealed that broadly neutralizing antibodies (bnAbs) against HIV-1 have unusually high levels of somatic hypermutation, long CDRH3 domains, and the ability to target one of four sites of vulnerability on the HIV-1 envelope (Env) glycoproteins. A current priority is to understand how bnAbs are generated during natural infection, and translate this information into immunogens that can elicit bnAb following vaccination. Recent Findings Strain-specific neutralizing antibodies (nAb) can acquire broad neutralizing capacity when the transmitted/founder Env or a specific Env variant is recognized by an unmutated rearranged germline that has the capacity to develop bnAb like features. This could be a relatively infrequent event, as only certain germlines appear to possess inherent features needed for bnAb activity. Furthermore, the glycosylation pattern and diversity of circulating HIV-1 Envs, as well as the state of the B cell compartment, may influence the activation and maturation of certain antibody lineages. Summary Collectively, studies over the last year suggest that the development of HIV-1 Env immunogens that bind and activate bnAb-like germlines is feasible. However, more information about the features of Env variants and the host factors that lead to breadth during natural infection is needed to elicit bnAbs through immunization. PMID:24662931

  18. Selective Expansion of Viral Variants following Experimental Transmission of a Reconstituted Feline Immunodeficiency Virus Quasispecies

    PubMed Central

    Willett, Brian J.; Kraase, Martin; Logan, Nicola; McMonagle, Elizabeth; Varela, Mariana; Hosie, Margaret J.

    2013-01-01

    Following long-term infection with virus derived from the pathogenic GL8 molecular clone of feline immunodeficiency virus (FIV), a range of viral variants emerged with distinct modes of interaction with the viral receptors CD134 and CXCR4, and sensitivities to neutralizing antibodies. In order to assess whether this viral diversity would be maintained following subsequent transmission, a synthetic quasispecies was reconstituted comprising molecular clones bearing envs from six viral variants and its replicative capacity compared in vivo with a clonal preparation of the parent virus. Infection with either clonal (Group 1) or diverse (Group 2) challenge viruses, resulted in a reduction in CD4+ lymphocytes and an increase in CD8+ lymphocytes. Proviral loads were similar in both study groups, peaking by 10 weeks post-infection, a higher plateau (set-point) being achieved and maintained in study Group 1. Marked differences in the ability of individual viral variants to replicate were noted in Group 2; those most similar to GL8 achieved higher viral loads while variants such as the chimaeras bearing the B14 and B28 Envs grew less well. The defective replication of these variants was not due to suppression by the humoral immune response as virus neutralising antibodies were not elicited within the study period. Similarly, although potent cellular immune responses were detected against determinants in Env, no qualitative differences were revealed between animals infected with either the clonal or the diverse inocula. However, in vitro studies indicated that the reduced replicative capacity of variants B14 and B28 in vivo was associated with altered interactions between the viruses and the viral receptor and co-receptor. The data suggest that viral variants with GL8-like characteristics have an early, replicative advantage and should provide the focus for future vaccine development. PMID:23372784

  19. Immunopathogenic events in acute infection of rhesus monkeys with simian immunodeficiency virus of macaques.

    PubMed Central

    Reimann, K A; Tenner-Racz, K; Racz, P; Montefiori, D C; Yasutomi, Y; Lin, W; Ransil, B J; Letvin, N L

    1994-01-01

    Infection of the rhesus monkey with simian immunodeficiency virus of macaques (SIVmax) was employed to explore the early immune events associated with the initial containment of an acute AIDS virus infection. In nine rhesus monkeys infected intravenously with uncloned SIVmac strain 251, high-level p27 plasma antigenemia was usually detected transiently from approximately day 7 through day 21 following virus inoculation. SIVmac replication in lymph nodes measured by in situ RNA hybridization closely paralleled the time course and magnitude of viremia. The containment of SIVmac spread by 3 to 4 weeks following infection suggests an efficient, early immune control of this virus infection. Anti-SIVmac antibodies were first detected in the blood at approximately day 14. At the time antigenemia was decreased or cleared, SIVmac neutralizing antibodies were present. A rise in circulating and lymph node CD8+ T cells also occurred coincident with the clearance of antigenemia and persisted thereafter. These CD8+ lymphocytes in lymph nodes had increased expression of both major histocompatibility complex class II and the adhesion molecule LFA-1; they also demonstrated decreased expression of the naive T-cell-associated CD45RA molecule. SIVmac-specific cytotoxic T-lymphocyte precursors were detected in both blood and lymph node by 7 days post-virus inoculation. These studies indicate that both virus-specific humoral and cellular immune mechanisms in blood and lymph node are associated with the clearance of viremia that occurs within the first month of infection of rhesus monkeys with SIVmac. Images PMID:8139022

  20. Neutral density profiles in argon helicon plasmas

    Microsoft Academic Search

    Amy M. Keesee

    2006-01-01

    A diode laser-based laser-induced fluorescence (LIF) diagnostic has been developed that can measure three species; argon neutrals, argon ions, and helium neutrals. This diagnostic has been combined with passive emission spectroscopy and a neutral argon collisional-radiative (CR) model to measure ground state radial density profiles of argon atoms in a helicon source. We have found the ground state neutral argon

  1. Plasma/Neutral-Beam Etching Apparatus

    NASA Technical Reports Server (NTRS)

    Langer, William; Cohen, Samuel; Cuthbertson, John; Manos, Dennis; Motley, Robert

    1989-01-01

    Energies of neutral particles controllable. Apparatus developed to produce intense beams of reactant atoms for simulating low-Earth-orbit oxygen erosion, for studying beam-gas collisions, and for etching semiconductor substrates. Neutral beam formed by neutralization and reflection of accelerated plasma on metal plate. Plasma ejected from coaxial plasma gun toward neutralizing plate, where turned into beam of atoms or molecules and aimed at substrate to be etched.

  2. Network Neutrality and Provider Investment Incentives

    Microsoft Academic Search

    J. Musacchio; J. Walrand; G. Schwartz

    2007-01-01

    This paper develops and analyzes a game theoretic model to study how the network regime (neutral or non-neutral) affects provider investment incentives, network quality and user prices. We formulate the conditions under which a non-neutral network is more favorable for providers and users. Our results indicate that the non-neutral regime is more favorable when the advertising rate is either low

  3. Inherited and acquired immunodeficiencies underlying tuberculosis in childhood.

    PubMed

    Boisson-Dupuis, Stéphanie; Bustamante, Jacinta; El-Baghdadi, Jamila; Camcioglu, Yildiz; Parvaneh, Nima; El Azbaoui, Safaa; Agader, Aomar; Hassani, Amal; El Hafidi, Naima; Mrani, Nidal Alaoui; Jouhadi, Zineb; Ailal, Fatima; Najib, Jilali; Reisli, Ismail; Zamani, Adil; Yosunkaya, Sebnem; Gulle-Girit, Saniye; Yildiran, Alisan; Cipe, Funda Erol; Torun, Selda Hancerli; Metin, Ayse; Atikan, Basak Yildiz; Hatipoglu, Nevin; Aydogmus, Cigdem; Kilic, Sara Sebnem; Dogu, Figen; Karaca, Neslihan; Aksu, Guzide; Kutukculer, Necil; Keser-Emiroglu, Melike; Somer, Ayper; Tanir, Gonul; Aytekin, Caner; Adimi, Parisa; Mahdaviani, Seyed Alireza; Mamishi, Setareh; Bousfiha, Aziz; Sanal, Ozden; Mansouri, Davood; Casanova, Jean-Laurent; Abel, Laurent

    2015-03-01

    Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-? immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey. PMID:25703555

  4. NMR Structure of the Myristylated Feline Immunodeficiency Virus Matrix Protein

    PubMed Central

    Brown, Lola A.; Cox, Cassiah; Baptiste, Janae; Summers, Holly; Button, Ryan; Bahlow, Kennedy; Spurrier, Vaughn; Kyser, Jenna; Luttge, Benjamin G.; Kuo, Lillian; Freed, Eric O.; Summers, Michael F.

    2015-01-01

    Membrane targeting by the Gag proteins of the human immunodeficiency viruses (HIV types-1 and -2) is mediated by Gag’s N-terminally myristylated matrix (MA) domain and is dependent on cellular phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]. To determine if other lentiviruses employ a similar membrane targeting mechanism, we initiated studies of the feline immunodeficiency virus (FIV), a widespread feline pathogen with potential utility for development of human therapeutics. Bacterial co-translational myristylation was facilitated by mutation of two amino acids near the amino-terminus of the protein (Q5A/G6S; myrMAQ5A/G6S). These substitutions did not affect virus assembly or release from transfected cells. NMR studies revealed that the myristyl group is buried within a hydrophobic pocket in a manner that is structurally similar to that observed for the myristylated HIV-1 protein. Comparisons with a recent crystal structure of the unmyristylated FIV protein [myr(-)MA] indicate that only small changes in helix orientation are required to accommodate the sequestered myr group. Depletion of PI(4,5)P2 from the plasma membrane of FIV-infected CRFK cells inhibited production of FIV particles, indicating that, like HIV, FIV hijacks the PI(4,5)P2 cellular signaling system to direct intracellular Gag trafficking during virus assembly. PMID:25941825

  5. Somatic reversion in DOCK8 immunodeficiency modulates disease phenotype

    PubMed Central

    Jing, Huie; Zhang, Qian; Zhang, Yu; Hill, Brenna J.; Dove, Christopher G.; Gelfand, Erwin W.; Atkinson, T. Prescott; Uzel, Gulbu; Matthews, Helen F.; Mustillo, Peter J.; Lewis, David B.; Kavadas, Fotini D.; Hanson, I. Celine; Kumar, Ashish R.; Geha, Raif S.; Douek, Daniel C.; Holland, Steven M.; Freeman, Alexandra F.; Su, Helen C.

    2014-01-01

    Background Autosomal recessive, loss-of-function mutations in DOCK8 cause a combined immunodeficiency characterized by atopy, recurrent infections, and cancer susceptibility. A genotype-phenotype explanation for the variable disease expression is lacking. Objective We investigated whether reversions contributed to the variable disease expression. Methods Patients followed at the NIH Clinical Center were studied. We performed detailed genetic analyses and intracellular flow cytometry to detect DOCK8 protein expression within lymphocyte subsets. Results We identified 17 out of 34 DOCK8-deficient patients who had germline mutations with variable degrees of reversion due to somatic repair. Somatic repair of the DOCK8 mutations resulted from second-site mutation, original-site mutation, gene conversion, and intragenic crossover. Higher degrees of reversion were associated with recombination-mediated repair. DOCK8 expression was restored primarily within antigen-experienced T cells or in NK cells, but less so in naïve T cells or B cells. Several patients exhibited multiple different repair events. Patients who had reversions were older and had less severe allergic disease, although infection susceptibility persisted. No patients were cured without hematopoietic cell transplantation. Conclusions In DOCK8 deficiency, only certain combinations of germline mutations supported secondary somatic repair. Those patients had an ameliorated disease course with longer survival, but still had fatal complications or required hematopoietic cell transplantation. These observations support the concept that some DOCK8 immunodeficient patients have mutable mosaic genomes that may modulate disease phenotype over time. PMID:24797421

  6. Cytomegalovirus pneumonia as the first manifestation of severe combined immunodeficiency

    PubMed Central

    Jo?czyk-Potoczna, Katarzyna; Ossowska, Lidia; Br?borowicz, Anna; Bartkowska-?niatkowska, Alicja; Wachowiak, Jacek

    2014-01-01

    Severe combined immunodeficiency (SCID) is characterized by the absence of functional T lymphocytes and impairment of adaptive immunity. While heterogeneity of the genetic background in SCID leads to the variability of immune phenotypes, most of affected newborns appear healthy but within the first few months they develop life-threatening opportunistic respiratory or gastrointestinal tract infections. The objective of the study was to define the presenting features and etiology of infections in children with SCID. We retrospectively reviewed five children in whom the diagnosis of SCID had been established in our pediatric immunology clinic over the last 10-year period. A viral respiratory tract infection was the first manifestation of SCID in all the children studied. Cytomegalovirus (CMV) pneumonia was recognized in as many as 4 cases and coronavirus pulmonary infection was diagnosed in one case, whereas Pneumocystis jiroveci was identified as a co-pathogen in one CMV-infected patient. Severe combined immunodeficiency is a pediatric emergency condition and given the significant impact of pulmonary CMV infection in SCID children, establishing an accurate etiological diagnosis is of essential importance in instituting the specific treatment and improving the outcome.

  7. Factors affecting cellular tropism of human immunodeficiency virus.

    PubMed Central

    Kim, S; Ikeuchi, K; Groopman, J; Baltimore, D

    1990-01-01

    To evaluate the basis of the slow growth of many human immunodeficiency virus strains in monocytes/macrophages, various stages of the virus life cycle have been studied for their possible contribution to viral tropism. Although we found that monocytic U937 cells had a higher percentage of CD4-positive cells than T-lymphoid H9 cells, the human immunodeficiency virus strain grew much less efficiently in the monocytic line. Viral tropism was primarily determined during the early stages of the virus cycle, that is, sometime between binding of the virus to the cell surface and reverse transcription of viral genomic RNA. Once the virus entered the host cell, reverse transcription, use of the long terminal repeat, RNA expression, and production of virus particles was about as efficient in monocytes as in T cells. Thus, during viral entry into the host cell cytoplasm there is a major limiting event that is particularly inefficient in U937 cells and possibly in all monocytes/macrophages. Images PMID:1976823

  8. Mucosal and systemic candidiasis in congenitally immunodeficient mice.

    PubMed Central

    Cantorna, M T; Balish, E

    1990-01-01

    Colony counts and light microscopy were used to assess the capacity of Candida albicans to colonize, infect the alimentary tract, and cause disseminated disease in athymic (nu/nu), euthymic (nu/+), beige (bg/bg), black (bg/+), beige athymic (bg/bg nu/nu), or beige euthymic (bg/bg nu/+) germfree mice. The alimentary tracts of all six genotypes of germfree mice were quickly colonized after exposure to yeast-phase C. albicans. Only bg/bg nu/nu mice showed obvious morbidity and mortality after mucosal colonization with C. albicans. Histopathology of C. albicans-colonized immunocompetent (nu/+, bg/+) and singly immunodeficient (nu/nu, bg/bg, bg/bg nu/+) mice showed minimal to moderate mucosal infections, whereas doubly immunodeficient (bg/bg nu/nu) mice showed extensive yeast and hyphal infection of the palate, tongue, esophagus, and stomach. A progressive systemic infection in C. albicans-colonized mice occurred only in bg/bg nu/nu mice 12 to 16 weeks after colonization and mucosal infection. Thus, it appears that a combination of defective cell-mediated immunity and phagocytic cell defects (polymorphonuclear leukocytes and/or macrophages) predisposed mice to severe mucosal and systemic candidiasis of endogenous origin. This is the first report of a mouse strain that is not only naturally susceptible to mucosal and systemic candidiasis of endogenous origin but also shows lethality at early (1 to 4 weeks) and late (12 to 16 weeks) times after alimentary tract colonization. Images PMID:2180820

  9. Simian Immunodeficiency Virus Interactions with Macaque Dendritic Cells

    PubMed Central

    Derby, Nina; Martinelli, Elena; Pugach, Pavel; Calenda, Giulia; Robbiani, Melissa

    2013-01-01

    This chapter summarizes advances in the following areas: (1) dendritic cell (DC)-mediated simian immunodeficiency virus (SIV) transmission, (2) role of DCs in innate and adaptive immunity against SIV, and (3) approaches to harness DC function to induce anti-SIV responses. The nonhuman primate (NHP) model of human immunodeficiency virus (HIV) infection in rhesus macaques and other Asian NHP species is highly relevant to advance the understanding of virus–host interactions critical for transmission and disease pathogenesis. HIV infection is associated with changes in frequency, phenotype, and function of the two principal subsets of DCs, myeloid DCs and plasmacytoid DCs. DC biology during pathogenic SIV infection is strikingly similar to that observed in HIV-infected patients. The NHP models provide an opportunity to dissect the requirements for DC-driven SIV infection and to understand how SIV distorts the DC system to its advantage. Furthermore, the SIV model of mucosal transmission enables the study of the earliest events of infection at the portal of entry that cannot be studied in humans, and, importantly, the involvement of DCs. Nonpathogenic infection in African NHP hosts allows investigations into the role of DCs in disease control. Understanding how DCs are altered during SIV infection is critical to the design of therapeutic and preventative strategies against HIV. PMID:22975875

  10. When less is more: primary immunodeficiency with an autoinflammatory kick

    PubMed Central

    Giannelou, Angeliki; Zhou, Qing; Kastner, Daniel L.

    2014-01-01

    Purpose of review Next-generation sequencing is revolutionizing the molecular taxonomy of human disease. Recent studies of patients with unexplained autoinflammatory disorders reveal germline genetic mutations that target important regulators of innate immunity. Recent findings Whole-exome analyses of previously undiagnosed patients have catalyzed the recognition of two new disease genes. First, a phenotypic spectrum, including livedo racemosa, fever with early-onset stroke, polyarteritis nodosa, and Sneddon syndrome, is caused by loss-of-function mutations in cat eye syndrome chromosome region, candidate 1 (CECR1), encoding adenosine deaminase 2. Adenosine deaminase 2 is a secreted protein expressed primarily in myeloid cells, and a regulator of macrophage differentiation and endothelial development. Disease-associated mutations impair anti-inflammatory M2 macrophage differentiation. Second, patients presenting with cold-induced urticaria, granulomatous rash, autoantibodies, and common variable immunodeficiency, or with blistering skin lesions, bronchiolitis, enterocolitis, ocular inflammation, and mild immunodeficiency harbor distinct mutations in phospholipase C?2, encoding a signaling molecule expressed in natural killer cells, mast cells, and B lymphocytes. These mutations inhibit the function of a phospholipase C?2 autoinhibitory domain, causing increased or constitutive signaling. Summary These findings underscore the power of next-generation sequencing, demonstrating how the primary deficiency of key molecular regulators or even regulatory motifs may lead to autoinflammation, and suggesting a possible role for cat eye syndrome chromosome region, candidate 1 and phospholipase C?2 in common diseases. PMID:25337682

  11. Coulomb Blockade with Neutral Modes

    NASA Astrophysics Data System (ADS)

    Kamenev, Alex; Gefen, Yuval

    2015-04-01

    We study transport through a quantum dot in the fractional quantum Hall regime with filling factors ? =2 /3 and ? =5 /2 , weakly coupled to the leads. We account for both injection of electrons to or from the leads, and quasiparticle rearrangement processes between the edge and the bulk of the quantum dot. The presence of neutral modes introduces topological constraints that modify qualitatively the features of the Coulomb blockade (CB). The periodicity of CB peak spacings doubles and the ratio of spacing between adjacent peaks approaches (in the low temperature and large dot limit) a universal value: 2 ?1 for ? =2 /3 and 3 ?1 for ? =5 /2 . The corresponding CB diamonds alternate their width in the direction of the bias voltage and allow for the determination of the neutral mode velocity, and of the topological numbers associated with it.

  12. Coulomb blockade with neutral modes.

    PubMed

    Kamenev, Alex; Gefen, Yuval

    2015-04-17

    We study transport through a quantum dot in the fractional quantum Hall regime with filling factors ?=2/3 and ?=5/2, weakly coupled to the leads. We account for both injection of electrons to or from the leads, and quasiparticle rearrangement processes between the edge and the bulk of the quantum dot. The presence of neutral modes introduces topological constraints that modify qualitatively the features of the Coulomb blockade (CB). The periodicity of CB peak spacings doubles and the ratio of spacing between adjacent peaks approaches (in the low temperature and large dot limit) a universal value: 2?1 for ?=2/3 and 3?1 for ?=5/2. The corresponding CB diamonds alternate their width in the direction of the bias voltage and allow for the determination of the neutral mode velocity, and of the topological numbers associated with it. PMID:25933323

  13. Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys.

    PubMed

    Barouch, Dan H; Whitney, James B; Moldt, Brian; Klein, Florian; Oliveira, Thiago Y; Liu, Jinyan; Stephenson, Kathryn E; Chang, Hui-Wen; Shekhar, Karthik; Gupta, Sanjana; Nkolola, Joseph P; Seaman, Michael S; Smith, Kaitlin M; Borducchi, Erica N; Cabral, Crystal; Smith, Jeffrey Y; Blackmore, Stephen; Sanisetty, Srisowmya; Perry, James R; Beck, Matthew; Lewis, Mark G; Rinaldi, William; Chakraborty, Arup K; Poignard, Pascal; Nussenzweig, Michel C; Burton, Dennis R

    2013-11-14

    Human immunodeficiency virus type 1 (HIV-1)-specific monoclonal antibodies with extraordinary potency and breadth have recently been described. In humanized mice, combinations of monoclonal antibodies have been shown to suppress viraemia, but the therapeutic potential of these monoclonal antibodies has not yet been evaluated in primates with an intact immune system. Here we show that administration of a cocktail of HIV-1-specific monoclonal antibodies, as well as the single glycan-dependent monoclonal antibody PGT121, resulted in a rapid and precipitous decline of plasma viraemia to undetectable levels in rhesus monkeys chronically infected with the pathogenic simian-human immunodeficiency virus SHIV-SF162P3. A single monoclonal antibody infusion afforded up to a 3.1 log decline of plasma viral RNA in 7?days and also reduced proviral DNA in peripheral blood, gastrointestinal mucosa and lymph nodes without the development of viral resistance. Moreover, after monoclonal antibody administration, host Gag-specific T-lymphocyte responses showed improved functionality. Virus rebounded in most animals after a median of 56?days when serum monoclonal antibody titres had declined to undetectable levels, although, notably, a subset of animals maintained long-term virological control in the absence of further monoclonal antibody infusions. These data demonstrate a profound therapeutic effect of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys as well as an impact on host immune responses. Our findings strongly encourage the investigation of monoclonal antibody therapy for HIV-1 in humans. PMID:24172905

  14. Understanding Neutral Genomic Molecular Clocks

    Microsoft Academic Search

    Soojin V. Yi

    2007-01-01

    The molecular clock hypothesis is a central concept in molecular evolution and has inspired much research into why evolutionary\\u000a rates vary between and within genomes. In the age of modern comparative genomics, understanding the neutral genomic molecular\\u000a clock occupies a critical place. It has been demonstrated that molecular clocks run differently between closely related species,\\u000a and generation time is an

  15. Imaging space plasmas in energetic neutral atoms

    Microsoft Academic Search

    E. C. Roelof; R. Demajistre; D. G. Mitchell; P. C Son Brandt

    2004-01-01

    Many space plasmas contain energetic singly-charged ions immersed in a cold gas of neutral atoms and molecules. When the energetic ions undergo charge-exchange collisions with the background cold neutrals, they become energetic neutral atoms (ENAs). Thus the space plasma Â\\

  16. Priming Effects for Affective vs. Neutral Faces

    ERIC Educational Resources Information Center

    Burton, Leslie A.; Rabin, Laura; Wyatt, Gwinne; Frohlich, Jonathan; Vardy, Susan B.; Dimitri, Diana

    2005-01-01

    Affective and Neutral Tasks (faces with negative or neutral content, with different lighting and orientation) requiring reaction time judgments of poser identity were administered to 32 participants. Speed and accuracy were better for the Affective than Neutral Task, consistent with literature suggesting facilitation of performance by affective…

  17. Separation of neutral carbohydrates by capillary electrophoresis

    Microsoft Academic Search

    Susumu Honda

    1996-01-01

    The basic strategies for analysis of neutral carbohydrates by capillary electrophoresis are summarized. Neutral carbohydrates are dissociated in strong alkali to give anions, hence they can be separated directly by zone electrophoresis based on the difference between their dissociation constants. However, neutral carbohydrates are not electrically charged under normal conditions. Therefore, they should be converted to ions prior to or

  18. Lymph Node Co-Infection of Mycobacterium Avium Complex and Cytomegalovirus in an Acquired Immunodeficiency Syndrome Patient

    PubMed Central

    Hedjazi, Arya; Hosseini, Marzieh; Hoseinzadeh, Amin

    2013-01-01

    Acquired immunodeficiency syndrome patients are known to have an increased tendency for developing opportunistic infections. However, there are no reports of simultaneous lymph node involvement of cytomegalovirus and Mycobacterium avium complex in a human immunodeficiency virus-positive patient. We report a 31-year-old man who presented with acute abdominal pain and tenderness and weight loss. He died a few hours after admission. Autopsy studies showed coinfection of cytomegalovirus, Mycobacterium avium complex and human immunodeficiency virus. Our case emphasizes the need to be careful in evaluating opportunistic infections in severely immunodepressed acquired immunodeficiency syndrome patients. This case report is the first manifestation of acquired immunodeficiency syndrome in this patient. PMID:24470953

  19. Phenotypic studies on recombinant human immunodeficiency virus type 1 (HIV-1) containing CRF01_AE env gene derived from HIV-1-infected patient, residing in central Thailand.

    PubMed

    Utachee, Piraporn; Jinnopat, Piyamat; Isarangkura-Na-Ayuthaya, Panasda; de Silva, U Chandimal; Nakamura, Shota; Siripanyaphinyo, Uamporn; Wichukchinda, Nuanjun; Tokunaga, Kenzo; Yasunaga, Teruo; Sawanpanyalert, Pathom; Ikuta, Kazuyoshi; Auwanit, Wattana; Kameoka, Masanori

    2009-03-01

    Human immunodeficiency virus type 1 (HIV-1) env genes were cloned from blood samples of HIV-1-infected Thai patients, and 35 infectious CRF01_AE envelope glycoprotein (Env)-recombinant viruses were established. In this report, we examined the neutralization susceptibility of these viruses to human monoclonal antibodies, 2G12, IgG1 b12, 2F5 and 4E10, pooled patient plasma, coreceptor antagonists and fusion inhibitor, T-20. The neutralization susceptibility of CRF01_AE Env-recombinant viruses to 2F5, 4E10, patient plasma, coreceptor antagonists and T-20 varied, while most viruses showed low susceptibility to 2G12 and IgG1 b12. Several dual-tropic viruses showed lower susceptibility to 2F5 and 4E10 than CXCR4- or CCR5-tropic viruses. Neutralization susceptibility of the CRF01_AE Env-recombinant virus to pooled patient plasma was negatively correlated with the length of the V1/V2 region or the number of potential N-linked glycosylation sites in conserved regions of gp120. No correlation was found between the coreceptor usage and neutralization susceptibility of the virus to T-20, whereas several dual-tropic viruses showed higher susceptibility to coreceptor antagonists than CXCR4- or CCR5-tropic viruses. We propose that these CRF01_AE Env-recombinant viruses are useful to further study the molecular mechanism of the susceptibility of CRF01_AE Env to neutralizing antibodies and viral entry inhibitors. PMID:19136072

  20. Induction of Humoral Immune Responses following Vaccination with Envelope-Containing, Formaldehyde-Treated, Thermally Inactivated Human Immunodeficiency Virus Type 1

    PubMed Central

    Poon, B.; Safrit, J. T.; McClure, H.; Kitchen, C.; Hsu, J. F.; Gudeman, V.; Petropoulos, C.; Wrin, T.; Chen, I. S. Y.; Grovit-Ferbas, K.

    2005-01-01

    The lack of success of subunit human immunodeficiency virus type 1 (HIV-1) vaccines to date suggests that multiple components or a complex virion structure may be required. We previously demonstrated retention of the major conformational epitopes of HIV-1 envelope following thermal treatment of virions. Moreover, antibody binding to some of these epitopes was significantly enhanced following thermal treatment. These included the neutralizing epitopes identified by monoclonal antibodies 1b12, 2G12, and 17b, some of which have been postulated to be partially occluded or cryptic in native virions. Based upon this finding, we hypothesized that a killed HIV vaccine could be derived to elicit protective humoral immune responses. Shedding of HIV-1 envelope has been described for some strains of HIV-1 and has been cited as one of the major impediments to developing an inactivated HIV-1 vaccine. In the present study, we demonstrate that treatment of virions with low-dose formaldehyde prior to thermal inactivation retains the association of viral envelope with virions. Moreover, mice and nonhuman primates vaccinated with formaldehyde-treated, thermally inactivated virions produce antibodies capable of neutralizing heterologous strains of HIV in peripheral blood mononuclear cell-, MAGI cell-, and U87-based infectivity assays. These data indicate that it is possible to create an immunogen by using formaldehyde-treated, thermally inactivated HIV-1 virions to induce neutralizing antibodies. These findings have broad implications for vaccine development. PMID:15795278

  1. UCLA1, a synthetic derivative of a gp120 RNA aptamer, inhibits entry of human immunodeficiency virus type 1 subtype C.

    PubMed

    Mufhandu, Hazel T; Gray, Elin S; Madiga, Maphuti C; Tumba, Nancy; Alexandre, Kabamba B; Khoza, Thandeka; Wibmer, Constantinos Kurt; Moore, Penny L; Morris, Lynn; Khati, Makobetsa

    2012-05-01

    Entry of human immunodeficiency virus type 1 (HIV-1) into cells is mediated by the virion surface envelope (Env) glycoproteins, making it a desirable target for antiretroviral entry inhibitors. We previously isolated a family of gp120 binding RNA aptamers and showed that they neutralized the infectivity of HIV-1. In this study, we assessed the activity of a shortened synthetic derivative of the B40 aptamer, called UCLA1, against a large panel of HIV-1 subtype C viruses. UCLA1 tightly bound to a consensus HIV-1 subtype C gp120 and neutralized isolates of the same subtype with 50% inhibitory concentrations (IC(50)s) in the nanomolar range. The aptamer had little toxicity in tests with cell lines and primary cells. Furthermore, it exhibited high therapeutic indices, suggesting that it may be effective at very low doses. Mapping of UCLA1 binding sites on gp120 revealed eight amino acid residues that modulated neutralization resistance. This included residues within the coreceptor binding site, at the base of the V3 loop, and in the bridging sheet within the conserved V1/V2 stem-loop of gp120. The aptamer was also shown to have synergistic effects with T20, a gp41 fusion inhibitor, and IgG1b12 (b12), an anti-CD4 binding site monoclonal antibody. These results suggest that UCLA1 may be suitable for development as a potent HIV-1 entry inhibitor. PMID:22379083

  2. Mucosal Priming with a Replicating-Vaccinia Virus-Based Vaccine Elicits Protective Immunity to Simian Immunodeficiency Virus Challenge in Rhesus Monkeys

    PubMed Central

    Sun, Caijun; Tang, Xian; Zhang, Yinfeng; Feng, Liqiang; Du, Yanhua; Xiao, Lijun; Liu, Li; Zhu, Weijun; Chen, Ling

    2013-01-01

    Mucosal surfaces are not targeted by most human immunodeficiency virus type 1 (HIV-1) vaccines, despite being major routes for HIV-1 transmission. Here we report a novel vaccination regimen consisting of a mucosal prime with a modified replicating vaccinia virus Tiantan strain (MVTTSIVgpe) and an intramuscular boost with a nonreplicating adenovirus strain (Ad5SIVgpe). This regimen elicited robust cellular immune responses with enhanced magnitudes, sustainability, and polyfunctionality, as well as higher titers of neutralizing antibodies against the simian immunodeficiency virus SIVmac1A11 in rhesus monkeys. The reductions in peak and set-point viral loads were significant in most animals, with one other animal being protected fully from high-dose intrarectal inoculation of SIVmac239. Furthermore, the animals vaccinated with this regimen were healthy, while ?75% of control animals developed simian AIDS. The protective effects correlated with the vaccine-elicited SIV-specific CD8+ T cell responses against Gag and Pol. Our study provides a novel strategy for developing an HIV-1 vaccine by using the combination of a replicating vector and mucosal priming. PMID:23487457

  3. Human immunodeficiency virus contains an epitope immunoreactive with thymosin. cap alpha. /sub 1/ and the 30-amino acid synthetic p17 group-specific antigen peptide HGP-30

    SciTech Connect

    Naylor, P.H.; Naylor, C.W.; Badamchian, M.; Wada, S.; Goldstein, A.L.; Wang, S.S.; Sun, D.K.; Thornton, A.H.; Sarin, P.S.

    1987-05-01

    The authors have reported that an antiserum prepared against thymosin ..cap alpha../sub 1/ (which shares a region of homology with the p17 protein of the acquired immunodeficiency syndrome (AIDS)-associated human immunodeficiency virus) effectively neutralized the AIDs virus and prevented its replication in H9 cells. Using HPLC and immunoblot analysis, they have identified from a clone B, type III human T-lymphotropic virus (HTLV-IIIB) extracts a protein with a molecular weight of 17,000 that is immunoreactive with thymosin ..cap alpha../sub 1/. In contrast, no immunoreactivity was found in retroviral extracts from a number of nonhuman species including feline, bovine, simian, gibbon, and murine retroviruses. Heterologous antiserum prepared against a 30-amino acid synthetic peptide analogue (HGP-30) does not cross-react with thymosin ..cap alpha../sub 1/ but does react specifically with the p17 protein of the AIDS virus in a manner identical to that seen with an HTLV-IIIB p17-specific monoclonal antibody. The demonstration that this synthetic analogue is immunogenic and that antibodies to HGP-30 cross-react not only with synthetic peptide but also with the HTLV-IIIB p17 viral protein provides an additional, and potentially more specific, candidate for development of a synthetic peptide vaccine for AIDS. In addition, the p17 synthetic peptide (HGP-3) may prove to be useful in a diagnostic assay for the detection of AIDS virus infection in seronegative individuals.

  4. Mucosal priming with a replicating-vaccinia virus-based vaccine elicits protective immunity to simian immunodeficiency virus challenge in rhesus monkeys.

    PubMed

    Sun, Caijun; Chen, Zhiwei; Tang, Xian; Zhang, Yinfeng; Feng, Liqiang; Du, Yanhua; Xiao, Lijun; Liu, Li; Zhu, Weijun; Chen, Ling; Zhang, Linqi

    2013-05-01

    Mucosal surfaces are not targeted by most human immunodeficiency virus type 1 (HIV-1) vaccines, despite being major routes for HIV-1 transmission. Here we report a novel vaccination regimen consisting of a mucosal prime with a modified replicating vaccinia virus Tiantan strain (MVTT(SIVgpe)) and an intramuscular boost with a nonreplicating adenovirus strain (Ad5(SIVgpe)). This regimen elicited robust cellular immune responses with enhanced magnitudes, sustainability, and polyfunctionality, as well as higher titers of neutralizing antibodies against the simian immunodeficiency virus SIV(mac1A11) in rhesus monkeys. The reductions in peak and set-point viral loads were significant in most animals, with one other animal being protected fully from high-dose intrarectal inoculation of SIV(mac239). Furthermore, the animals vaccinated with this regimen were healthy, while ~75% of control animals developed simian AIDS. The protective effects correlated with the vaccine-elicited SIV-specific CD8(+) T cell responses against Gag and Pol. Our study provides a novel strategy for developing an HIV-1 vaccine by using the combination of a replicating vector and mucosal priming. PMID:23487457

  5. Histoplasmosis in Patients With Cell-Mediated Immunodeficiency: Human Immunodeficiency Virus Infection, Organ Transplantation, and Tumor Necrosis Factor-? Inhibition

    PubMed Central

    Luckett, Keith; Dummer, J. Stephen; Miller, Geraldine; Hester, Sydney; Thomas, Lora

    2015-01-01

    Background.?Histoplasmosis causes severe disease in patients with defects of cell-mediated immunity. It is not known whether outcomes vary related to the type of immunodeficiency or class of antifungal treatment. Methods.?We reviewed cases of active histoplasmosis that occurred at Vanderbilt University Medical Center from July 1999 to June 2012 in patients with human immunodeficiency virus (HIV) infection, a history of transplantation, or tumor necrosis factor (TNF)-? inhibitor use. These groups were compared for differences in clinical presentation and outcomes. In addition, outcomes were related to the initial choice of treatment. Results.?Ninety cases were identified (56 HIV, 23 transplant, 11 TNF-? inhibitor). Tumor necrosis factor-? patients had milder disease, shorter courses of therapy, and fewer relapses than HIV patients. Histoplasma antigenuria was highly prevalent in all groups (HIV 88%, transplant 95%, TNF-? 91%). Organ transplant recipients received amphotericin B formulation as initial therapy less often than other groups (22% vs 57% HIV vs 55% TNF-?; P = .006). Treatment failures only occurred in patients with severe disease. The failure rate was similar whether patients received initial amphotericin or triazole therapy. Ninety-day histoplasmosis-related mortality was 9% for all groups and did not vary significantly with choice of initial treatment. Conclusions.?Histoplasmosis caused milder disease in patients receiving TNF-? inhibitors than patients with HIV or solid organ transplantation. Treatment failures and mortality only occurred in patients with severe disease and did not vary based on type of immunosuppression or choice of initial therapy.

  6. Histoplasmosis in Patients With Cell-Mediated Immunodeficiency: Human Immunodeficiency Virus Infection, Organ Transplantation, and Tumor Necrosis Factor-? Inhibition.

    PubMed

    Luckett, Keith; Dummer, J Stephen; Miller, Geraldine; Hester, Sydney; Thomas, Lora

    2015-01-01

    Background. ?Histoplasmosis causes severe disease in patients with defects of cell-mediated immunity. It is not known whether outcomes vary related to the type of immunodeficiency or class of antifungal treatment. Methods. ?We reviewed cases of active histoplasmosis that occurred at Vanderbilt University Medical Center from July 1999 to June 2012 in patients with human immunodeficiency virus (HIV) infection, a history of transplantation, or tumor necrosis factor (TNF)-? inhibitor use. These groups were compared for differences in clinical presentation and outcomes. In addition, outcomes were related to the initial choice of treatment. Results. ?Ninety cases were identified (56 HIV, 23 transplant, 11 TNF-? inhibitor). Tumor necrosis factor-? patients had milder disease, shorter courses of therapy, and fewer relapses than HIV patients. Histoplasma antigenuria was highly prevalent in all groups (HIV 88%, transplant 95%, TNF-? 91%). Organ transplant recipients received amphotericin B formulation as initial therapy less often than other groups (22% vs 57% HIV vs 55% TNF-?; P = .006). Treatment failures only occurred in patients with severe disease. The failure rate was similar whether patients received initial amphotericin or triazole therapy. Ninety-day histoplasmosis-related mortality was 9% for all groups and did not vary significantly with choice of initial treatment. Conclusions. ?Histoplasmosis caused milder disease in patients receiving TNF-? inhibitors than patients with HIV or solid organ transplantation. Treatment failures and mortality only occurred in patients with severe disease and did not vary based on type of immunosuppression or choice of initial therapy. PMID:26034750

  7. Nonlinear neutral inclusions: assemblages of coated ellipsoids

    PubMed Central

    Bolaños, Silvia Jiménez; Vernescu, Bogdan

    2015-01-01

    The problem of determining nonlinear neutral inclusions in (electrical or thermal) conductivity is considered. Neutral inclusions, inserted in a matrix containing a uniform applied electric field, do not disturb the field outside the inclusions. The well-known Hashin-coated sphere construction is an example of a neutral inclusion. In this paper, we consider the problem of constructing neutral inclusions from nonlinear materials. In particular, we discuss assemblages of coated ellipsoids. The proposed construction is neutral for a given applied field. PMID:26064633

  8. HIV-specific humoral and cellular immunity in rabbits vaccinated with recombinant human immunodeficiency virus-like gag-env particles

    SciTech Connect

    Haffar, O.K.; Smithgall, M.D.; Moran, P.A.; Travis, B.M.; Zarling, J.M.; Hu, S.L. (Department of Virology, Bristol-Myers Squibb Pharmaceutical Research Institute-Seattle, WA (USA))

    1991-08-01

    Recombinant human immunodeficiency virus type-1 (HIV-1)-like gag-env particles produced in mammalian cells were inoculated into two New Zealand white rabbits. In parallel, two control rabbits were inoculated with the homologous HIV-1 virions inactivated by ultraviolet light (uv) and psoralen treatments. The humoral and cellular immune responses to HIV-1 were evaluated for both groups of animals. Recombinant particles elicited humoral immunity that was specific for all the viral structural proteins. The antibodies recognized both denatured and nondenatured proteins. Moreover, the sera neutralized the in vitro infectivity of the homologous virus in CEM cells. Importantly, the recombinant particles also generated a T helper response by priming with the HIV proteins. Similar results were observed with inactivated virus immunization. Therefore, the authors results suggest that the recombinant HIV-like particles elicit functional humoral immunity as well as cellular immunity and represent a novel vaccine candidate for AIDS.

  9. Three difficult cases: the challenge of autoimmunity, immunodeficiency and recurrent infections in patients with Good syndrome.

    PubMed

    Arnold, S J; Hodgson, T; Misbah, S A; Patel, S Y; Cooper, S M; Venning, V A

    2015-03-01

    Good syndrome (GS) is a rare, adult-acquired primary combined immunodeficiency syndrome arising in the context of previous or current thymoma. Patients with GS frequently develop recurrent sinopulmonary infections and are also at high risk of autoimmune manifestations, including skin conditions such as lichen planus. We report three middle-aged patients with GS complicated by multiple autoimmune and infectious manifestations. The combination of immunodeficiency, autoimmunity and recurrent infections seen in patients with GS continues to present a management challenge, particularly in patients with oral mucosal disease and recurrent candidiasis. Clinicians should be prompted to investigate an underlying immunodeficiency in patients with multiple autoimmune conditions and recurrent sinopulmonary infections. PMID:25059810

  10. Neutral gas dynamics in fireballs

    SciTech Connect

    Stenzel, R. L. [Department of Physics and Astronomy, University of California, Los Angeles, California 90095-1547 (United States); Ionita, C.; Schrittwieser, R. [University of Innsbruck, Department for Ion Physics and Applied Physics, A-6020 Innsbruck (Austria)

    2011-06-01

    Fireballs are local discharge phenomena on positively biased electrodes in partially ionized plasmas. Electrons, energized at a double layer, heat neutral gas which expands. The gas pressure exceeds the plasma pressure, hence becomes important to the stability and transport in fireballs. The flow of gas moves the electrode and sensors similar to a mica pendulum. Flow speed and directions are measured. A fireball gun has been developed to partially collimate the flow of hot gas and heat objects in its path. New applications of fireballs are suggested.

  11. Space station neutral external environment

    NASA Technical Reports Server (NTRS)

    Ehlers, H.; Leger, L.

    1988-01-01

    Molecular contamination levels arising from the external induced neutral environment of the Space Station (Phase 1 configuration) were calculated using the MOLFLUX model. Predicted molecular column densities and deposition rates generally meet the Space Station contamination requirements. In the doubtful cases of deposition due to materials outgassing, proper material selection, generally excluding organic products exposed to the external environment, must be considered to meet contamination requirements. It is important that the Space Station configuration, once defined, is not significantly modified to avoid introducing new unacceptable contamination sources.

  12. Heterogeneity of stem cells in severe combined immunodeficiency.

    PubMed Central

    Incefy, G S; Grimes, E; Kagan, W A; Goldstein, G; Smithwick, E; O'Reilly, R; Good, R A

    1976-01-01

    Two patients with severe combined immunodeficiency disease (SCID) having variable B-cell development have been shown to have marrow precursors of lymphoid cells which can be induced in vitro by thymic factors to express certain T-cell surface characteristics (HTLA+ phenotypes). Their marrow cells could not, however, be induced by these same factors to develop the E-rosette marker or functional activities of T lymphocytes. The marrow of these children also showed, when compared to that of normal adults, a different distribution of cellular elements on density gradient fractionation. The findings support the view that the disorder under study has a different pathogenesis from other forms of SCID previously analysed. Images Fig. 4 PMID:786520

  13. Sexual Assault: A Report on Human Immunodeficiency Virus Postexposure Prophylaxis

    PubMed Central

    Griffith, William F.; Ackerman, Gary E.; Zoellner, Cindy L.; Sheffield, Jeanne S.

    2010-01-01

    The objective of this report is to describe an urban county hospital human immunodeficiency virus (HIV) infection prevention protocol offering prophylactic combination antiretroviral medications to female victims of sexual assault. A retrospective chart review was conducted from June, 2007 through June, 2008 of 151 women who were prescribed antiretroviral prophylaxis by protocol. All women receiving HIV prophylaxis initially screened HIV seronegative. Of the 58 women who reported taking any HIV prophylaxis, 36 (62%) were HIV screened at 12 and/or 24 weeks and none had HIV seroconverted. Although the initiation of an HIV post exposure prophylaxis protocol for sexual assault in a county hospital population is feasible, patient follow-up for counseling and HIV serostatus evaluation is an identified barrier PMID:20706678

  14. Pathogenesis and treatment of human immunodeficiency virus lipodystrophy

    PubMed Central

    Jain, Suyog Subhash; Ramteke, Karuna Balwant; Raparti, Girish Tulsidas; Kalra, Sanjay

    2012-01-01

    Enhanced understanding about the way human immunodeficiency virus (HIV) infects and causes infection in humans has led to invention and use of newer more effective antiretroviral drugs. As treatment for HIV is long term, side effects of the antiretrovirals become an important area of research focus. Antiretrovirals can cause severe metabolic abnormalities, collectively known as HIV lipodystrophy syndrome. If untreated, these metabolic abnormalities have the potential to increase stroke and cardiac ischemia. Management includes choice of nonoffending drugs, switch over to less toxic drugs, hypolipidemics, oral antidiabetics including thiazolidinediones, metformin and growth hormone analogs and finally facial surgeries. Updated knowledge about HIV lipodystrophy, and the hormone-related drugs used to treat it, is essential for physicians and endocrinologists to be able to diagnose the patients and effectively treat them. PMID:22701839

  15. Overview of Microbicides for the prevention of human immunodeficiency virus

    PubMed Central

    Abdool Karim, Salim S.; Baxter, Cheryl

    2012-01-01

    Human immunodeficiency virus (HIV) prevention tools that women can use and control are urgently needed. Microbicides are chemical products applied to the vagina or rectum to prevent the sexual transmission of HIV. Four classes of candidate microbicides have been tested to date: those that (1) enhance the natural defences in the vagina to inactivate HIV; (2) inactivate HIV in the vagina; (3) prevent HIV from attaching to, and fusing with, the host cells; and (4) prevent HIV from replicating in genital tract host cells. Despite numerous disappointing efficacy trial results over the past 20 years, substantial progress is now being made in microbicide development after the release of the CAPRISA 004 trial, which provided proof-of-concept that topical antiretroviral microbicides can prevent sexual transmission of HIV and herpes simplex type-2 infection. Microbicides, which fill an important gap for women-controlled prevention methods, have the potential to alter the course of the HIV pandemic. PMID:22386823

  16. Penicillium marneffei infection in patients infected with human immunodeficiency virus.

    PubMed

    Supparatpinyo, K; Chiewchanvit, S; Hirunsri, P; Uthammachai, C; Nelson, K E; Sirisanthana, T

    1992-04-01

    From June 1990 to August 1991, 21 patients infected with the human immunodeficiency virus (HIV) presented with systemic mycosis caused by Penicillium marneffei. Between August 1987 and August 1991, only five patients were observed who had P. marneffei infection but not HIV infection. The clinical presentation included fever, cough, and generalized papular skin lesions. For 11 of these 21 patients, the presumptive diagnosis of P. marneffei infection could be made by microscopic examination of Wright's-stained bone marrow aspirate and/or touch smears of skin specimens obtained by biopsy several days before the results of culture were available. Initial clinical response to treatment with either parenteral amphotericin B or oral itraconazole was favorable in most patients. Epidemiological and clinical evidence suggest that this systemic mycosis is caused by an important opportunistic pathogen and that it should be included in the differential diagnosis of AIDS, at least for countries in areas of endemicity, i.e., Southeast Asia and China. PMID:1315586

  17. Glanzmann Thrombasthenia Associated with Human Immunodeficiency Virus-Positive Patient

    PubMed Central

    Manne, Rakesh Kumar; Natarajan, Kannan; Patil, Rajendra; Prathi, Venkata Sarath; Beeraka, Swapna Sridevi; Kolaparthi, Venkata Suneel Kumar

    2014-01-01

    Glanzmann's thrombasthenia (GT) is an autosomal recessive inherited platelet function defect characterized by normal platelet count, prolonged bleeding time and abnormal clot retraction. This disease typically presents in infancy or early childhood and has proven to have very good prognosis. In this case study, a 22-year-old GT patient who also developed human immunodeficiency virus (HIV) infection after sometime is reported. The patient showed oral manifestations of gingival hyperplasia and petechial lesions. Unfortunately the detection of both thrombasthenia and HIV were done at considerably late stages which contributed to a poor prognosis. The patient died of cardiopulmonary arrest secondary to HIV, thrombasthenia and thrombocytopenia. The importance of early detection, supportive care and communication between the general and oral physician in management of the GT is also discussed. PMID:24829739

  18. Glanzmann thrombasthenia associated with human immunodeficiency virus-positive patient.

    PubMed

    Manne, Rakesh Kumar; Natarajan, Kannan; Patil, Rajendra; Prathi, Venkata Sarath; Beeraka, Swapna Sridevi; Kolaparthi, Venkata Suneel Kumar

    2014-04-01

    Glanzmann's thrombasthenia (GT) is an autosomal recessive inherited platelet function defect characterized by normal platelet count, prolonged bleeding time and abnormal clot retraction. This disease typically presents in infancy or early childhood and has proven to have very good prognosis. In this case study, a 22-year-old GT patient who also developed human immunodeficiency virus (HIV) infection after sometime is reported. The patient showed oral manifestations of gingival hyperplasia and petechial lesions. Unfortunately the detection of both thrombasthenia and HIV were done at considerably late stages which contributed to a poor prognosis. The patient died of cardiopulmonary arrest secondary to HIV, thrombasthenia and thrombocytopenia. The importance of early detection, supportive care and communication between the general and oral physician in management of the GT is also discussed. PMID:24829739

  19. Chronic actinic dermatitis associated with human immunodeficiency virus infection.

    PubMed

    Meola, T; Sanchez, M; Lim, H W; Buchness, M R; Soter, N A

    1997-09-01

    Chronic actinic dermatitis is a photodistributed, eczematous dermatitis that preferentially affects elderly men and persists for months to years. Its occurrence in individuals infected with human immunodeficiency virus (HIV) has been described in five patients. We report four additional cases of this uncommon, chronic photodermatosis associated with HIV infection. In two of the patients, photosensitivity was a presenting disorder leading to the diagnosis of HIV infection. All patients were men of skin type VI with a mean age of 50 years, all had decreased minimal erythema doses to ultraviolet B, three of the four patients had decreased minimal erythema doses to ultraviolet A and all had CD4 cell counts of < 200 x 10(6)/L. PMID:9349344

  20. Transplantation Outcomes for Severe Combined Immunodeficiency, 2000–2009

    PubMed Central

    Pai, Sung-Yun; Logan, Brent R.; Griffith, Linda M.; Buckley, Rebecca H.; Parrott, Roberta E.; Dvorak, Christopher C.; Kapoor, Neena; Hanson, Imelda C.; Filipovich, Alexandra H.; Jyonouchi, Soma; Sullivan, Kathleen E.; Small, Trudy N.; Burroughs, Lauri; Skoda-Smith, Suzanne; Haight, Ann E.; Grizzle, Audrey; Pulsipher, Michael A.; Chan, Ka Wah; Fuleihan, Ramsay L.; Haddad, Elie; Loechelt, Brett; Aquino, Victor M.; Gillio, Alfred; Davis, Jeffrey; Knutsen, Alan; Smith, Angela R.; Moore, Theodore B.; Schroeder, Marlis L.; Goldman, Frederick D.; Connelly, James A.; Porteus, Matthew H.; Xiang, Qun; Shearer, William T.; Fleisher, Thomas A.; Kohn, Donald B.; Puck, Jennifer M.; Notarangelo, Luigi D.; Cowan, Morton J.; O’Reilly, Richard J.

    2014-01-01

    BACKGROUND The Primary Immune Deficiency Treatment Consortium was formed to analyze the results of hematopoietic-cell transplantation in children with severe combined immunodeficiency (SCID) and other primary immunodeficiencies. Factors associated with a good transplantation outcome need to be identified in order to design safer and more effective curative therapy, particularly for children with SCID diagnosed at birth. METHODS We collected data retrospectively from 240 infants with SCID who had received transplants at 25 centers during a 10-year period (2000 through 2009). RESULTS Survival at 5 years, freedom from immunoglobulin substitution, and CD3+ T-cell and IgA recovery were more likely among recipients of grafts from matched sibling donors than among recipients of grafts from alternative donors. However, the survival rate was high regardless of donor type among infants who received transplants at 3.5 months of age or younger (94%) and among older infants without prior infection (90%) or with infection that had resolved (82%). Among actively infected infants without a matched sibling donor, survival was best among recipients of haploidentical T-cell–depleted transplants in the absence of any pretransplantation conditioning. Among survivors, reduced-intensity or myeloablative pre-transplantation conditioning was associated with an increased likelihood of a CD3+ T-cell count of more than 1000 per cubic millimeter, freedom from immunoglobulin substitution, and IgA recovery but did not significantly affect CD4+ T-cell recovery or recovery of phytohemagglutinin-induced T-cell proliferation. The genetic subtype of SCID affected the quality of CD3+ T-cell recovery but not survival. CONCLUSIONS Transplants from donors other than matched siblings were associated with excellent survival among infants with SCID identified before the onset of infection. All available graft sources are expected to lead to excellent survival among asymptomatic infants. (Funded by the National Institute of Allergy and Infectious Diseases and others.) PMID:25075835

  1. Non-M Variants of Human Immunodeficiency Virus Type 1

    PubMed Central

    Mourez, Thomas; Simon, François

    2013-01-01

    SUMMARY The AIDS pandemic that started in the early 1980s is due to human immunodeficiency virus type 1 (HIV-1) group M (HIV-M), but apart from this major group, many divergent variants have been described (HIV-1 groups N, O, and P and HIV-2). The four HIV-1 groups arose from independent cross-species transmission of the simian immunodeficiency viruses (SIVs) SIVcpz, infecting chimpanzees, and SIVgor, infecting gorillas. This, together with human adaptation, accounts for their genomic, phylogenetic, and virological specificities. Nevertheless, the natural course of non-M HIV infection seems similar to that of HIV-M. The virological monitoring of infected patients is now possible with commercial kits, but their therapeutic management remains complex. All non-M variants were principally described for patients linked to Cameroon, where HIV-O accounts for 1% of all HIV infections; only 15 cases of HIV-N infection and 2 HIV-P infections have been reported. Despite improvements in our knowledge, many fascinating questions remain concerning the origin, genetic evolution, and slow spread of these variants. Other variants may already exist or may arise in the future, calling for close surveillance. This review provides a comprehensive, up-to-date summary of the current knowledge on these pathogens, including the historical background of their discovery; the latest advances in the comprehension of their origin and spread; and clinical, therapeutic, and laboratory aspects that may be useful for the management and the treatment of patients infected with these divergent viruses. PMID:23824367

  2. Immunodeficiency Among Children with Recurrent Invasive Pneumococcal Disease

    PubMed Central

    Schejbel, Lone; Lundstedt, A.C.; Jensen, Lise; Laursen, Inga A.; Ryder, Lars P.; Heegaard, Niels H.H.; Konradsen, Helle; Christensen, Jens Jørgen; Heilmann, Carsten; Marquart, Hanne V.

    2015-01-01

    Background: Recurrent invasive pneumococcal disease (rIPD) occurs mostly in children with an underlying disease, but some cases remain unexplained. Immunodeficiency has been described in children with rIPD, but the prevalence is unknown. We used a nationwide registry of all laboratory-confirmed cases of rIPD to identify cases of unexplained rIPD and examine them for immunodeficiency. Methods: Cases of rIPD in children 0–15 years of age from 1980 to 2008 were identified. Children without an obvious underlying disease were screened for complement function, T-cell, B-cell, natural killer--cell counts and concentration of immunoglobulins. B-cell function was evaluated by measuring antibody response to polysaccharide-based pneumococcal vaccination and the extent of fraction of somatic hypermutation. Toll-Like receptor (TLR) signaling function and mutations in key TLR-signaling molecules were examined. Results: In total, rIPD were observed in 54 children (68 cases of rIPD of 2192 IPD cases). Children with classical risk factors for IPD were excluded, and among the remaining 22 children, 15 were eligible for analysis. Of these 6 (40%) were complement C2-deficient. Impaired vaccination response was found in 6 children of whom 3 were C2 deficient. One patient had a severe TLR signaling dysfunction. No mutations in IRAK4, IKBKG or MYD88 were found. Conclusion: Of an unselected cohort of children with rIPD at least 11% were C2 deficient. Data suggest that screening for complement deficiencies and deficient antibody response to pneumococcal vaccines in patients with more than 1 episode of IPD is warranted. PMID:25831419

  3. Virologic and immunologic aspects of acquired immunodeficiency syndrome.

    PubMed

    Lane, H C

    1990-01-01

    From the initial clinical descriptions of the acquired immunodeficiency syndrome (AIDS) in 1981 to the present time, much has been discovered concerning the epidemiologic factors, pathogenesis, treatment and prevention of this disease. Recent advances in epidemiology have included a better understanding of the occupational risk of human immunodeficiency virus (HIV) infection after percutaneous exposure (responsible for approximately 0.4 per cent of instances), an appreciation of the potential variability in the time interval between infection and seroconversion (generally on the order of three months but occasionally longer) and establishment of the need for intimate contact to transmit infection. Following the discovery of HIV-1 as the etiologic agent of AIDS, many rapid advances have been possible including the development of screening tests, elucidation of the HIV-1 genome and the discovery that the CD4 T lymphocyte is the predominant cell destroyed by HIV-1. Progressive destruction of CD4 T cells results in a progressive decline in immunologic function that may take a variety of clinical forms, ranging from no symptoms to severe opportunistic infections. The delineation of the life cycle of HIV-1 has helped in the development of antiretroviral therapies, including agents that interfere with reverse transcription (nucleoside analogues, such as zidovudine, dideoxycytidine, dideoxyinosine and azidodideoxyuridine) and agents that interfere with viral assembly (protease inhibitors and interferon alpha). A more precise understanding of the nature of the immune response elicited after HIV-1 infection has resulted in the development of several candidate HIV-1 vaccines, including recombinant vaccinia viruses expressing the HIV-1 envelope and recombinant envelope proteins. PMID:1978762

  4. Clinical mite infestations of domestic cats seropositive for feline immunodeficiency and/or feline leukemia viruses 

    E-print Network

    Simmons, Christian Eric

    2000-01-01

    Feline immunodeficiency virus (FIV) and Feline leukemia virus (FeLV) are both immunosuppressive viruses that compromise the ability of a feline host to combat foreign parhogens. Skin infections caused by parasitic mites are often observed among...

  5. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype...

  6. Redox-Driven Events in the Human Immunodeficiency Virus Type 1 (HIV-1) Infection and their Clinical Implications.

    PubMed

    Colado Simao, Andrea Name; Victorino, Vanessa Jacob; Morimoto, Helena K; Reiche, Edna Maria Vissoci; Panis, Carolina

    2015-01-01

    Oxidative stress is a condition characterized by the imbalance between the production of reactive species (RS) or free radicals and their neutralization by the antioxidant defenses, leading to the accumulation of RS and their derived metabolites, with changes in the redox status of the cell. These RS can act on biological components and induce the oxidative and nitrosative reactions on lipids, proteins, and DNA. In this context, a wide variety of chronic diseases present oxidative stress as a part of the pathogenesis, including the human immunodeficiency virus type 1 (HIV-1) infection. The relationship between oxidative stress and HIV-1 infection lies in the fact that the RS species are important components of the innate immune response, and their derived metabolites and reactions participate in several events of the adaptative immune response. On the other hand, studies have shown specific roles for oxidative-driven events in both the host immunity and the virus biology. Undoubtedly, the occurrence of oxidative stress in HIV-1-infected patients has been implicated in disease progression, as well as in developing other secondary disorders, such as cardiovascular diseases, insulin resistance, and metabolic syndrome. This review aims to characterize the redox-driven events in the HIV-1 infection and their clinical implications in the disease features. PMID:25771095

  7. Cellular Gene Expression Profiles in Rhesus Macaques Challenged Mucosally with a Pathogenic R5 Tropic Simian Human Immunodeficiency Virus Isolate

    PubMed Central

    Pise-Masison, Cynthia A.; Radonovich, Michael F.; Brady, John; Lee, Jae K.; Cheon, Soo-Young; Markham, Phillip; Cristillo, Anthony; Pal, Ranajit

    2008-01-01

    Abstract Insights into the host factors that contribute to an effective antiviral immune response may be obtained by examining global gene expression in simian human immunodeficiency virus (SHIV)-infected nonhuman primates that exhibit different virological outcomes. Immune responses and gene expression profiles in peripheral blood mononuclear cells (PBMCs) were compared between animals that controlled or did not control viremia after infection. Rectal inoculation of eight rhesus macaques with R5-tropic SHIVSF162P3 resulted in a high level of plasma viremia during the acute phase of infection. The viremia was controlled to below levels of detection in six of these animals at the set point (controllers), whereas two animals had persistent viremia throughout the 140 wk that the animals were monitored (non-controllers). CD4+ T-cell counts declined slightly in both controllers and non-controllers in the acute phase of infection, but CD4+ T-cell counts continued to decline only in the non-controllers. Neutralizing antibodies to the challenge virus were variable and could not account for the control of viremia. However, analysis of the cellular gene expression profiles in the PBMCs from both groups of animals revealed distinctive gene expression patterns between controllers and non-controllers. Using the paired LPE test, 59 genes with p values <0.01 were identified and specific differences in the gene expression profiles in PBMCs from controllers versus non-controllers were detected. PMID:19115930

  8. Prevention of immunodeficiency virus induced CD4+ T-cell depletion by prior infection with a non-pathogenic virus

    SciTech Connect

    TerWee, Julie A.; Carlson, Jennifer K.; Sprague, Wendy S.; Sondgeroth, Kerry S.; Shropshire, Sarah B.; Troyer, Jennifer L. [Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado (United States); VandeWoude, Sue [Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado (United States)], E-mail: suev@lamar.colostate.edu

    2008-07-20

    Immune dysregulation initiated by a profound loss of CD4+ T-cells is fundamental to HIV-induced pathogenesis. Infection of domestic cats with a non-pathogenic lentivirus prevalent in the puma (puma lentivirus, PLV or FIV{sub PCO}) prevented peripheral blood CD4+ T-cell depletion caused by subsequent virulent FIV infection. Maintenance of this critical population was not associated with a significant decrease in FIV viremia, lending support to the hypothesis that direct viral cytopathic effect is not the primary cause of immunodeficiency. Although this approach was analogous to immunization with a modified live vaccine, correlates of immunity such as a serum-neutralizing antibody or virus-specific T-cell proliferative response were not found in protected animals. Differences in cytokine transcription profile, most notably in interferon gamma, were observed between the protected and unprotected groups. These data provide support for the importance of non-adaptive enhancement of the immune response in the prevention of CD4+ T-cell loss.

  9. beta-Galactosidase containing a human immunodeficiency virus protease cleavage site is cleaved and inactivated by human immunodeficiency virus protease.

    PubMed Central

    Baum, E Z; Bebernitz, G A; Gluzman, Y

    1990-01-01

    A "cleavage cassette" specifying a decapeptide human immunodeficiency virus (HIV) protease cleavage site was introduced into six different locations of beta-galactosidase (beta-D-galactoside galactohydrolase, EC 3.2.1.23) in Escherichia coli. Four of these constructs retained beta-galactosidase activity despite the insertion of the cleavage cassette. Of these four constructs, one was cleaved by HIV protease, resulting in the inactivation of beta-galactosidase both in vivo and in vitro. This cleavage was inhibited by pepstatin A, a known inhibitor of HIV protease. Thus, beta-galactosidase has been converted into an easily assayed substrate for HIV protease. An analogous construct of beta-galactosidase containing a polio protease cleavage site was cleaved likewise by polio protease, suggesting that this system may be generic for monitoring cleavage by a variety of proteases. Images PMID:2124694

  10. Genetic Variation in a Human Immunodeficiency Virus Type 2 Live-Virus Macaca nemestrina Vaccine Model

    Microsoft Academic Search

    ANTONIA RADAELLI; GUNTER KRAUS; PATRICIA BADEL; JAN MCCLURE; SHIU-LOK HU; WILLIAM MORTON; CARLO DE GIULI MORGHEN; FLOSSIE WONG-STAAL; D. LOONEY

    1998-01-01

    Four pigtailed macaques were inoculated with an infectious, apathogenic human immunodeficiency virus type 2 (HIV-2) molecular clone (HIV-2KR) and subsequently challenged with a highly pathogenic strain, HIV-2287, together with two naive control animals. After challenge, two animals inoculated with a high dose of the immunizing strain were protected from CD4 decline and immunodeficiency. To examine the role of genetic heterogeneity

  11. Selection of a Simian-Human Immunodeficiency Virus Strain Resistant to a Vaginal Microbicide in Macaques

    Microsoft Academic Search

    Dawn M. Dudley; Jennifer L. Wentzel; Matthew S. Lalonde; Ronald S. Veazey; Eric J. Arts

    2009-01-01

    PSC-RANTES binds to CCR5, inhibits human immunodeficiency virus type 1 (HIV-1) entry, and has been shown as a vaginal microbicide to protect rhesus macaques from a simian-human immunodeficiency virus chimera (SHIVSF162-p3) infection in a dose-dependent manner. In this study, env gene sequences from SHIVSF162-p3-infected rhesus macaques treated with PSC-RANTES were analyzed for possible drug escape variants. Two specific mutations located

  12. Low fidelity of cell-free DNA synthesis by reverse transcriptase of human immunodeficiency virus.

    PubMed Central

    Takeuchi, Y; Nagumo, T; Hoshino, H

    1988-01-01

    The fidelity of DNA synthesis by reverse transcriptases from human immunodeficiency virus and other retroviruses was compared by measuring the rates of misincorporation of dCMP in the place of TMP in cell-free DNA synthesis with polyadenylic acid as the template. The fidelity of human immunodeficiency virus reverse transcriptase was found to be about one-third of that of the reverse transcriptases of other retroviruses. Images PMID:2458489

  13. Case report: Esophageal histoplasmosis associated with disseminated tuberculosis in acquired immunodeficiency syndrome.

    PubMed

    Rezende, Rosamar Eulira Fontes; Brunaldi, Mariângela Ottoboni; Girão, Milena Santana; Zucoloto, Sérgio; Garcia, Sérgio Britto; Machado, Alcyone Artioli; Módena, José Luiz Pimenta

    2009-03-01

    Bacterial and fungal infections are common in acquired immunodeficiency syndrome (AIDS). Histoplasmosis is a common fungal disease in severely immunocompromised patients infected with human immunodeficiency virus (HIV) in endemic areas. In this population the most frequent form of presentation of histoplasmosis is disseminated, with the clinical manifestations being similar to those of disseminated tuberculosis. Esophageal histoplasmosis and the association of histoplasmosis with tuberculosis are infrequent. We report here a rare case of esophageal histoplasmosis associated with disseminated tuberculosis in AIDS. PMID:19270280

  14. Shared Usage of the Chemokine Receptor CXCR4 by the Feline and Human Immunodeficiency Viruses

    Microsoft Academic Search

    BRIAN J. WILLETT; LAURENT PICARD; MARGARET J. HOSIE; JULIE D. TURNER; KAREN ADEMA; PAUL R. CLAPHAM

    1997-01-01

    Feline immunodeficiency virus (FIV) induces a disease state in the domestic cat that is similar to AIDS in human immunodeficiency virus (HIV)-infected individuals. As with HIV, FIV can be divided into primary and cell culture-adapted isolates. Adaptation of FIV to replicate and form syncytia in the Crandell feline kidney (CrFK) cell line is accompanied by an increase in the net

  15. Liver Cancer in Transgenic Mice Carrying the Human ImmunodeficiencyVirus tat Gene1

    Microsoft Academic Search

    Jonathan Vogel; Steven H. Hinrichs; Laura A. Napolitano; Lien Ngo; Gilbert Jay

    1991-01-01

    Patients with the acquired immunodeficiency syndrome are at risk to develop a variety of different cancers. Based on epidemiológica! data, Kaposi's sarcoma and non-Hodgkin's lymphoma have been clearly asso ciated with infection by the human immunodeficiency virus (HIV). Ad ditional cancers such as basal cell and squamous cell carcinomas, mela noma, and hepatocellular carcinoma have also been reported to be

  16. Sensitivity and specificity of pooled versus individual sera in a human immunodeficiency virus antibody prevalence study.

    PubMed Central

    Cahoon-Young, B; Chandler, A; Livermore, T; Gaudino, J; Benjamin, R

    1989-01-01

    We evaluated the efficacy of testing pooled versus individual sera for the detection of human immunodeficiency virus antibody. A total of 5,000 individual specimens and 500 pools of 10 specimens each were assayed by an enzyme-linked immunosorbent assay. There was complete agreement in human immunodeficiency virus enzyme-linked immunosorbent assay reactivity for pooled versus individual specimens. An estimated savings of 60 to 80% (labor and supplies) can be realized dependent upon pooling and assay format. PMID:2504779

  17. Molecular clock on a neutral network.

    PubMed

    Raval, Alpan

    2007-09-28

    The number of fixed mutations accumulated in an evolving population often displays a variance that is significantly larger than the mean (the overdispersed molecular clock). By examining a generic evolutionary process on a neutral network of high-fitness genotypes, we establish a formalism for computing all cumulants of the full probability distribution of accumulated mutations in terms of graph properties of the neutral network, and use the formalism to prove overdispersion of the molecular clock. We further show that significant overdispersion arises naturally in evolution when the neutral network is highly sparse, exhibits large global fluctuations in neutrality, and small local fluctuations in neutrality. The results are also relevant for elucidating aspects of neutral network topology from empirical measurements of the substitution process. PMID:17930643

  18. Proline Is Not Uniquely Capable of Providing the Pivot Point for Domain Swapping in 2G12, a Broadly Neutralizing Antibody against HIV-1*

    PubMed Central

    Gach, Johannes S.; Furtmüller, Paul G.; Quendler, Heribert; Messner, Paul; Wagner, Ralf; Katinger, Hermann; Kunert, Renate

    2010-01-01

    The human monoclonal antibody 2G12 is a member of a small group of broadly neutralizing antibodies against human immunodeficiency virus type 1. 2G12 adopts a unique variable heavy domain-exchanged dimeric configuration that results in an extensive multivalent binding surface and the ability to bind with high affinity to densely clustered high mannose oligosaccharides on the “silent” face of the gp120 envelope glycoprotein. Here, we further define the amino acids responsible for this extraordinary domain-swapping event in 2G12. PMID:19903812

  19. [Prevalence, risk factors and genetic characterization of human T-cell lymphotropic virus types 1 and 2 in patients infected with human immunodeficiency virus type 1 in the cities of Ribeirão Preto and São Paulo].

    PubMed

    Kleine Neto, Walter; Sanabani, Sabri Saeed; Jamal, Leda Fátima; Sabino, Ester Cerdeira

    2009-01-01

    The aim of this study was to define the prevalence of human T cell lymphotropic virus types 1 and 2 in patients who were positive for human immunodeficiency virus type 1 in the State of São Paulo, Brazil. We evaluated 319 individuals infected with HIV type 1 who were attended at specialized clinics in two cities (Ribeirão Preto and São Paulo). The patients were interviewed and tested for antibodies against HTLV types 1 and 2 (Orthoâ HTLV-1/HTLV-2 Ab-Capture enzyme immunoassay). Direct DNA sequencing of polymerase chain reaction products from the tax region of HTLV type 2 and the long terminal repeat region of HTLV types 1 and 2 were performed to differentiate and determine the subtypes. The overall prevalence of anti-HTLV type 1 and 2 antibodies was 7.5% (24/319; 95% CI: 5.2-11.5). HTLV type 1 and 2 infection was associated with a history of injected drug use and with antibodies for hepatitis C virus (p < 0.001), but not with age (p = 0.2), sex (p = 0.9), sexual behavior or serological markers for sexually transmitted diseases (anti-Treponema pallidum, anti-human herpesvirus type 8 or anti-hepatitis B virus antibodies) (p > 0.05). HTLV DNA was detected in 13 out of 24 samples, of which 12 were characterized as HTLV subtype 2c and one as HTLV subtype 1a. Among the 12 HTLV type 2 samples, seven were from injected drug users, thus indicating that this route is an important risk factor for HTLV type 2 transmission among our population infected with HIV type 1. PMID:19684973

  20. Envelope glycans of immunodeficiency virions are almost entirely oligomannose antigens

    E-print Network

    Gleeson, Joseph G.

    and International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA to be a component of any successful AIDS vaccine (2, 7­9), and this glycoprotein has formed the basis of extensive generation of gp120 antigens used for vaccine trials. In the context of vaccine design, we also note that Man

  1. Neutral-beam current drive in tokamaks

    SciTech Connect

    Devoto, R.S.

    1986-01-01

    The theory of neutral-beam current drive in tokamaks is reviewed. Experiments are discussed where neutral beams have been used to drive current directly and also indirectly through neoclassical effects. Application of the theory to an experimental test reactor is described. It is shown that neutral beams formed from negative ions accelerated to 500 to 700 keV are needed for this device.

  2. EFFECTS OF LEAKAGE NEUTRAL PARTICLES ON SHOCKS

    SciTech Connect

    Ohira, Yutaka, E-mail: ohira@phys.aoyama.ac.jp [Department of Physics and Mathematics, Aoyama Gakuin University, 5-10-1 Fuchinobe, Sagamihara 252-5258 (Japan)

    2012-10-20

    In this paper, we investigate effects of neutral particles on shocks propagating into the partially ionized medium. We find that for 120 km s{sup -1} < u {sub sh} < 3000 km s{sup -1} (u {sub sh} is the shock velocity), about 10% of upstream neutral particles leak into the upstream region from the downstream region. Moreover, we investigate how the leakage neutral particles affect the upstream structure of the shock and particle accelerations. Using four-fluid approximations (upstream ions, upstream neutral particles, leakage neutral particles, and pickup ions), we provide analytical solutions of the precursor structure due to leakage neutral particles. It is shown that the upstream flow is decelerated in the precursor region and the shock compression ratio becomes smaller than without leakage neutral particles, but the total compression ratio does not change. Even if leakage of neutral particles is small (a few percent of total upstream particles), this smaller compression ratio of the shock can explain steep gamma-ray spectra from young supernova remnants. Furthermore, leakage neutral particles could amplify the magnetic field and heat the upstream region.

  3. Ergonomically neutral arm support system

    DOEpatents

    Siminovitch, Michael J; Chung, Jeffrey Y; Dellinges, Steven; Lafever, Robin E

    2005-08-02

    An ergonomic arm support system maintains a neutral position for the forearm. A mechanical support structure attached to a chair or other mounting structure supports the arms of a sitting or standing person. The system includes moving elements and tensioning elements to provide a dynamic balancing force against the forearms. The support structure is not fixed or locked in a rigid position, but is an active dynamic system that is maintained in equipoise by the continuous operation of the opposing forces. The support structure includes an armrest connected to a flexible linkage or articulated or pivoting assembly, which includes a tensioning element such as a spring. The pivoting assembly moves up and down, with the tensioning element providing the upward force that balances the downward force of the arm.

  4. Neutral Hydrogen in Arp 158

    E-print Network

    Mansie G. Iyer; Caroline E. Simpson; Stephen T. Gottesman; Benjamin K. Malphrus

    2004-05-20

    We present 21 cm observations of Arp 158. We have performed a study of the neutral hydrogen (HI) to help us understand the overall formation and evolution of this system. This is a disturbed system with distinct optical knots connected by a linear structure embedded in luminous material. There is also a diffuse spray to the southeast. The HI seems to be made up of three distinct, kinematically separate systems. Arp 158 bears a certain optical resemblance to NGC 520 (Arp 157), which has been identified as a mid-stage merger. From our 21 cm observations of Arp 158, we also see a comparable HI content with NGC 520. These similarities suggest that Arp 158 is also an intermediate stage merger.

  5. Modelling the Neutral Sodium Tails of Comets

    NASA Astrophysics Data System (ADS)

    Birkett, K. S.; Jones, G. H.; Coates, A. J.

    2014-12-01

    Neutral sodium is typically easy to detect in active comets around perihelion, due to the very high efficiency of the sodium D transition, and at some comets a distinct neutral sodium tail is observed. The first distinct neutral sodium tail images were apparent in comet Hale-Bopp (C/1995 O1) data taken using CoCam [Cremonese et al, 1997], but since this initial detection similar features have been observed at a number of near-Sun comets using the SOHO/LASCO coronagraph. An understanding of the distribution and evolution of neutral cometary sodium may best be developed using a combination of spectra and images in different filters at multiple times throughout a comet's orbit. At present the source of neutral sodium in comets is unknown, primarily because the evolution of neutral cometary sodium is difficult to intuitively predict due to the Swings and Greenstein effects. Several authors [review presented in Cremonese et al, 1999] have suggested various combinations of sources of neutral sodium in the nuclear region, near-nuclear region, dust tail and ion tail. In order to understand the wide variety of cometary observations of neutral sodium available we have developed the first fully three dimensional, heliocentric distance dependent, versatile Monte Carlo neutral sodium tail model (initially based on a model developed by [Brown et al, 1998]). Our model is known as COMPASS (Cometary Orbital Motion at Perihelion: an Adaptable Sodium Simulation), and incorporates the unintuitive variation in radiation pressure influences on sodium atoms with different heliocentric velocities. We present the initial results of a comparison between COMPASS and observational data. We have found good agreement between the overall morphology of the neutral sodium tail imaged at comet Hale-Bopp and COMPASS, and have begun to extend the study to other comets of interest. We also present a comparison between simulated COMPASS spectra and observations. The versatility of COMPASS allows it to be easily adapted to any other neutral cometary sodium tail observations available.

  6. Impact of Simian Immunodeficiency Virus Infection on Chimpanzee Population Dynamics

    PubMed Central

    Rudicell, Rebecca S.; Holland Jones, James; Wroblewski, Emily E.; Learn, Gerald H.; Li, Yingying; Robertson, Joel D.; Greengrass, Elizabeth; Grossmann, Falk; Kamenya, Shadrack; Pintea, Lilian; Mjungu, Deus C.; Lonsdorf, Elizabeth V.; Mosser, Anna; Lehman, Clarence; Collins, D. Anthony; Keele, Brandon F.; Goodall, Jane; Hahn, Beatrice H.; Pusey, Anne E.; Wilson, Michael L.

    2010-01-01

    Like human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus of chimpanzees (SIVcpz) can cause CD4+ T cell loss and premature death. Here, we used molecular surveillance tools and mathematical modeling to estimate the impact of SIVcpz infection on chimpanzee population dynamics. Habituated (Mitumba and Kasekela) and non-habituated (Kalande) chimpanzees were studied in Gombe National Park, Tanzania. Ape population sizes were determined from demographic records (Mitumba and Kasekela) or individual sightings and genotyping (Kalande), while SIVcpz prevalence rates were monitored using non-invasive methods. Between 2002–2009, the Mitumba and Kasekela communities experienced mean annual growth rates of 1.9% and 2.4%, respectively, while Kalande chimpanzees suffered a significant decline, with a mean growth rate of ?6.5% to ?7.4%, depending on population estimates. A rapid decline in Kalande was first noted in the 1990s and originally attributed to poaching and reduced food sources. However, between 2002–2009, we found a mean SIVcpz prevalence in Kalande of 46.1%, which was almost four times higher than the prevalence in Mitumba (12.7%) and Kasekela (12.1%). To explore whether SIVcpz contributed to the Kalande decline, we used empirically determined SIVcpz transmission probabilities as well as chimpanzee mortality, mating and migration data to model the effect of viral pathogenicity on chimpanzee population growth. Deterministic calculations indicated that a prevalence of greater than 3.4% would result in negative growth and eventual population extinction, even using conservative mortality estimates. However, stochastic models revealed that in representative populations, SIVcpz, and not its host species, frequently went extinct. High SIVcpz transmission probability and excess mortality reduced population persistence, while intercommunity migration often rescued infected communities, even when immigrating females had a chance of being SIVcpz infected. Together, these results suggest that the decline of the Kalande community was caused, at least in part, by high levels of SIVcpz infection. However, population extinction is not an inevitable consequence of SIVcpz infection, but depends on additional variables, such as migration, that promote survival. These findings are consistent with the uneven distribution of SIVcpz throughout central Africa and explain how chimpanzees in Gombe and elsewhere can be at equipoise with this pathogen. PMID:20886099

  7. Anti-human papillomavirus therapeutics: facts & future.

    PubMed

    Bharti, Alok C; Shukla, Shirish; Mahata, Sutapa; Hedau, Suresh; Das, Bhudev C

    2009-09-01

    Even after 25 years of establishing Human Papillomavirus (HPV) as the causative agent for cervical cancer, effective treatment of HPV infection still unavailable. Comprehensive efforts especially for targeting HPV infection have been made only in recent years. Conventional physical ablation of HPV-induced lesions such as cryo-therapy, photo-therapy, LEEP, laser cone-biopsy and localized radiotherapy are shown to be effective to some extent in treating localized lesions where the removal of diseased tissue is associated with removal of transforming keratinocytes harboring HPV. Apart from currently available prophylactic vaccines which prevent the viral entry and should be given prior to viral exposure, several attempts are being made to develop therapeutic vaccines that could treat prevailing HPV infection. In addition, immunomodulators like interferons and imiquimod that have been shown to elicit cytokine milieu to enhance host immune response against HPV infection. Also, antiviral approaches such as RNA interference (RNAi) nucleotide analogs, antioxidants and herbal derivatives have shown effective therapeutic potential against HPV infection. These leads are being tested in pre-clinical and clinical studies. Present article provides a brief overview of conventional therapies for HPV-associated diseases. Potential of non-ablative anti-HPV treatment modalities that could prove useful for either elimination of HPV in early stages of infection when the virus is not integrated into the host cell genome or suppression of the expression of viral oncogenes that dys-regulate the host cell cycle following transformation is discussed. PMID:19901439

  8. A self-consistent model of plasma and neutrals at Saturn: Neutral cloud morphology

    Microsoft Academic Search

    S. Jurac; J. D. Richardson

    2005-01-01

    We present a model of the plasma and neutral environment that treats plasma and neutrals self-consistently, using Voyager plasma and ultraviolet H observations and Hubble Space Telescope OH measurements as constraints. The neutral distributions are determined with a Monte Carlo model, and the plasma distributions are determined with a diffusive transport model including sources and losses. We find a larger

  9. Cytokine interactions in human immunodeficiency virus-infected individuals: roles of interleukin (IL)-2, IL-12, and IL-15

    PubMed Central

    1995-01-01

    Cytokines have been shown to be powerful regulators of the immune response. In this study, we analyze the effect that the newly recognized cytokine interleukin (IL)-15 has on proliferation and cytokine induction using peripheral blood mononuclear cells (PBMCs) and purified CD4+ T cells from patients infected with human immunodeficiency virus (HIV) who are at various stages in their disease. We observed that IL-15 enhances the proliferative response in a dose-dependent manner from PBMCs of HIV-infected individuals when stimulated by polyclonal mitogen, tetanus toxoid, or HIV-specific antigen. The effects of exogenous IL-15 are substantially diminished by adding a neutralizing antibody to the beta chain of the IL-2 receptor. Moreover, the ability of IL-15 to increase proliferation is enhanced by the presence of endogenous IL-2 produced in the cultures. The effect that exogenous IL-15 had on IL-2, IL-4, and interferon (IFN)-gamma induction from PBMC's or CD4+ T cells in response to mitogen or tetanus toxoid was also examined. This was compared to the effect that exogenous IL-2 and IL-12 had under the same conditions. Addition of IL- 2 or IL-15 to short-term in vitro cultures of either PBMCs or CD4+ T cells had little effect on IL-2, IL-4, or IFN-gamma production. By contrast, IL-12 caused substantial enhancement of both IL-2 and IFN- gamma production from these cultures. The role that endogenous cytokines have on IFN-gamma induction was also studied. Addition of a neutralizing antibody to the alpha chain of the IL-2 receptor or IL-12 to antigen stimulated cultures caused a striking decrease in IFN-gamma production. Neutralization of endogenous IL-15 also resulted in diminished IFN-gamma production from cultures stimulated with mitogen. IL-4 and IFN-gamma protein production by PBMCs and CD4+ T cells stimulated with mitogen was assessed to see if we could detect a specific bias of cytokine production. Small amounts of IL-4 were detected from CD4+ T cells but not PBMCs from most individuals tested. IFN-gamma and IL-2, however, were also produced from these same cultures. These results further elucidate the mechanism of cytokine regulation in HIV-infected individuals, and they provide evidence that IL-15 may be a useful immune modulator. PMID:7561680

  10. Implications of tritium in neutral beam injectors

    SciTech Connect

    Kim, J; Stewart, L D

    1980-01-01

    Neutral injectors for heating plasmas of D-T burning fusion reactors are subject to tritium contamination. This paper discusses relevant questions and problem areas pertinent to tritium environment, including calculations of tritium contaminations in different neutral injectors, gas handling and pumping systems, and implications on beam line components.

  11. Low energy neutral atoms in the magnetosphere

    Microsoft Academic Search

    T. E. Moore; M. R. Collier; J. L. Burch; D. J. Chornay; S. A. Fuselier; A. G. Ghielmetti; B. L. Giles; D. C. Hamilton; F. A. Herrero; J. W. Keller; K. W. Ogilvie; B. L. Peko; J. M. Quinn; T. M. Stephen; G. R. Wilson; P. Wurz

    2001-01-01

    We report observations of low energy neutral atoms (LENA) from the solar wind and the ionosphere, ob- tained by the LENA Imager on the IMAGE spacecraft. The LENA Imager detects and images LENAs arriving at the spacecraft from within a 90? field of view (8?x8? pixels), swept through 360? every twominutes by spacecraft spin. Neutral atoms arriving at the sensor

  12. Neutralism and selectionism: the molecular clock

    Microsoft Academic Search

    Francisco J. Ayala

    2000-01-01

    The neutrality theory predicts that the rate of molecular evolution will be constant over time, and thus that there is a molecular clock for timing evolutionary events. It has been observed that the variance of the rate of evolution is generally larger than expected according to the neutrality theory. Several modifications of the theory have been proposed to account for

  13. Economists’ Statement on Network Neutrality Policy

    Microsoft Academic Search

    William J. Baumol; Martin Cave; Peter Cramton; Robert W. Hahn; Thomas W. Hazlett; Paul L. Joskow; Alfred E. Kahn; Robert E. Litan; John Mayo; Patrick A. Messerlin; Bruce M. Owen; Robert S. Pindyck; Scott J. Savage; John Vernon; Scott Wallsten; Leonard Waverman; Lawrence J. White

    2007-01-01

    Network neutrality is a policy proposal that would regulate how network providers manage and price the use of their networks. Congress has introduced several bills on network neutrality. Proposed legislation generally would mandate that Internet service providers exercise no control over the content that flows over their lines and would bar providers from charging more for preferentially faster access to

  14. Neutralizing Activity of Saliva against Cytomegalovirus?

    PubMed Central

    Saccoccio, Frances M.; Gallagher, Mary K.; Adler, Stuart P.; McVoy, Michael A.

    2011-01-01

    Congenital cytomegalovirus (CMV) disease is the leading cause of permanent disability in neonates in the United States. Neutralizing antibodies in saliva may protect against maternal CMV infection by blocking viral entry into oral epithelial cells, but the antibody response to CMV in the saliva following natural infection is not well characterized. Saliva specimens from naturally infected individuals were tested for CMV-neutralizing activity using epithelial and fibroblast cells. Saliva from seronegative adults had no inherent anti-CMV activity. Neutralizing activity of saliva from naturally infected adults was not detectable using fibroblast cells, and saliva from young children, adolescents, and Towne vaccine recipients did not have activity using either cell type. However, when using epithelial cells, neutralizing activity was present in saliva from 50% of seropositive adults, correlated with serum-neutralizing activity, and was more prevalent in mothers of children in day care than in non-day care-associated adults. Three day care mothers with high salivary neutralizing activities (>1:20) had exceptionally high serum-neutralizing titers (3- to 8-fold higher than typical seropositives) and were immunoblot positive for serum antibodies to the epithelial entry mediator UL130. These results suggest that salivary neutralizing activities are attainable by induction of high serum IgG levels and could be utilized to evaluate candidate cytomegalovirus vaccines. PMID:21795465

  15. The Level of CD4 Expression Limits Infection of Primary Rhesus Monkey Macrophages by a T-Tropic Simian Immunodeficiency Virus and Macrophagetropic Human Immunodeficiency Viruses

    Microsoft Academic Search

    NORBERT BANNERT; DOMINIK SCHENTEN; STEWART CRAIG; JOSEPH SODROSKI

    2000-01-01

    The entry of primate immunodeficiency viruses into cells is dependent on the interaction of the viral envelope glycoproteins with receptors, CD4, and specific members of the chemokine receptor family. Although in many cases the tropism of these viruses is explained by the qualitative pattern of coreceptor expression, several instances have been observed where the expression of a coreceptor on the

  16. Vaccine-Induced Cellular Immune Responses Reduce Plasma Viral Concentrations after Repeated Low-Dose Challenge with Pathogenic Simian Immunodeficiency Virus SIVmac239

    PubMed Central

    Wilson, Nancy A.; Reed, Jason; Napoe, Gnankang S.; Piaskowski, Shari; Szymanski, Andy; Furlott, Jessica; Gonzalez, Edna J.; Yant, Levi J.; Maness, Nicholas J.; May, Gemma E.; Soma, Taeko; Reynolds, Matthew R.; Rakasz, Eva; Rudersdorf, Richard; McDermott, Adrian B.; O'Connor, David H.; Friedrich, Thomas C.; Allison, David B.; Patki, Amit; Picker, Louis J.; Burton, Dennis R.; Lin, Jing; Huang, Lingyi; Patel, Deepa; Heindecker, Gwendolyn; Fan, Jiang; Citron, Michael; Horton, Melanie; Wang, Fubao; Liang, Xiaoping; Shiver, John W.; Casimiro, Danilo R.; Watkins, David I.

    2006-01-01

    The goal of an AIDS vaccine regimen designed to induce cellular immune responses should be to reduce the viral set point and preserve memory CD4 lymphocytes. Here we investigated whether vaccine-induced cellular immunity in the absence of any Env-specific antibodies can control viral replication following multiple low-dose challenges with the highly pathogenic SIVmac239 isolate. Eight Mamu-A*01-positive Indian rhesus macaques were vaccinated with simian immunodeficiency virus (SIV) gag, tat, rev, and nef using a DNA prime-adenovirus boost strategy. Peak viremia (P = 0.007) and the chronic phase set point (P = 0.0192) were significantly decreased in the vaccinated cohort, out to 1 year postinfection. Loss of CD4+ memory populations was also ameliorated in vaccinated animals. Interestingly, only one of the eight vaccinees developed Env-specific neutralizing antibodies after infection. The control observed was significantly improved over that observed in animals vaccinated with SIV gag only. Vaccine-induced cellular immune responses can, therefore, exert a measure of control over replication of the AIDS virus in the complete absence of neutralizing antibody and give us hope that a vaccine designed to induce cellular immune responses might control viral replication. PMID:16731926

  17. Inhibition of purified CD34+ hematopoietic progenitor cells by human immunodeficiency virus 1 or gp120 mediated by endogenous transforming growth factor beta 1

    PubMed Central

    1996-01-01

    Human CD34+ hematopoietic progenitor cells, stringently purified from the peripheral blood of 20 normal donors, showed an impaired survival and clonogenic capacity after exposure to either heat-inactivated human immunodeficiency virus (HIV) 1 (strain IIIB) or cross-linked envelope gp120. Cell cycle analysis, performed at different times in serum-free liquid culture, showed an accumulation in G0/G1 in HIV-1- or gp120- treated cells and a progressive increase of cells with subdiploid DNA content, characteristic of apoptosis. In blocking experiments with anti- transforming growth factor (TGF) beta 1 neutralizing serum or TGF-beta 1 oligonucleotides, we demonstrated that the HIV-1- or gp120-mediated suppression of CD34+ cell growth was almost entirely due to an upregulation of endogenous TGF-beta 1 produced by purified hematopoietic progenitors. Moreover, by using a sensitive assay on the CCL64 cell line, increased levels of bioactive TGF-beta 1 were recovered in the culture supernatant of HIV-1/gp120-treated CD34+ cells. Anti-TGF-beta 1 neutralizing serum or TGF-beta 1 oligonucleotides were also effective in inducing a significant increase of the plating efficiency of CD34+ cells, purified from the peripheral blood of three HIV-1-seropositive individuals, suggesting that a similar mechanism may be also operative in vivo. The relevance of these findings to a better understanding of the pathogenesis of HIV-1-related cytopenias is discussed. PMID:8551249

  18. Immunodeficiency lentiviral infections in natural and non-natural hosts

    PubMed Central

    2011-01-01

    The host immune system is profoundly affected during the acute phase of progressive immunodeficiency lentiviral infections. Studies of these alterations have been quite restricted in humans because of the limited availability of samples from acutely HIV-infected persons. Therefore, numerous studies have turned attention to nonhuman primate models. Specifically, SIV-infected rhesus macaques (RMs) have been informative for understanding the pathogenesis of HIV infection in humans. Indeed, advantages of the nonhuman primate model include the ability to study the very early events after infection and the ability to retrieve copious amounts of tissues. In addition, nonhuman primates allow for comparative studies between non-natural and natural hosts for SIV, in which SIV infection results in progression, or not, to AIDS, respectively. Although SIV infection of RM is the best model for HIV infection, the immunologic and/or virologic phenomena in SIV-infected RM do not always reflect those seen in HIV-infected humans. Here virologic and immunologic aspects of acute HIV infection of humans and SIV infection of Asian and African nonhuman primates are discussed and compared in relation to how these aspects relate to disease progression. PMID:21505193

  19. Proteinuria in paediatric patients with human immunodeficiency virus infection.

    PubMed

    Giacomet, Vania; Erba, Paola; Di Nello, Francesca; Coletto, Sonia; Viganò, Alessandra; Zuccotti, Gianvincenzo

    2013-04-16

    In human immunodeficiency virus (HIV)-infected people kidney disease is as an important cause of morbidity and mortality. Clinical features of kidney damage in HIV-infected patients range from asymptomatic microalbuminuria to nephrotic syndrome. The lack of specific clinical features despite the presence of heavy proteinuria may mask the renal involvement. Indeed, it is important in HIV patients to monitor renal function to early discover a possible kidney injury. After the introduction of antiretroviral therapy, mortality and morbidity associated to HIV-infection have shown a substantial reduction, although a variety of side effects for long-term use of highly active antiretroviral therapy, including renal toxicity, has emerged. Among more than 20 currently available antiretroviral agents, many of them can occasionally cause reversible or irreversible nephrotoxicity. At now, three antiretroviral agents, i.e., indinavir, atazanavir and tenofovir disoproxil fumarate have a well established association with direct nephrotoxicity. This review focuses on major causes of proteinuria and other pathological findings related to kidney disease in HIV-infected children and adolescents. PMID:24303454

  20. Screening for Cognitive Impairment in Human Immunodeficiency Virus

    PubMed Central

    Paul, Robert; Chiao, Stephanie; Wendelken, Lauren A.; Miller, Bruce

    2011-01-01

    Recent publications estimate the prevalence of human immunodeficiency virus (HIV)–associated neurocognitive disorders (HAND) exceeds 50%, and this rate is likely higher among older patients. Cognitive impairment may impact medication adherence, and symptomatic impairment has been linked to all-cause mortality providing some impetus for early detection. There are currently insufficient data to inform solid recommendations on screening methods. Most HIV-specific tools have poor performance characteristics for all but the most severe form of impairment, which accounts for <5% of cases. Reliance on symptoms is likely to miss a substantial proportion of individuals with HAND due to poor insight, confounding mood disturbances, and lack of well-informed proxies. In the aging HIV-positive population, broader screening tools may be required to allow sensitivity for both HIV and neurodegenerative disorders. We describe the clinical presentation of HAND, review existing data related to screening tools, and provide preliminary and practical recommendations in the absence of more definitive studies. PMID:21921226

  1. Screening for cognitive impairment in human immunodeficiency virus.

    PubMed

    Valcour, Victor; Paul, Robert; Chiao, Stephanie; Wendelken, Lauren A; Miller, Bruce

    2011-10-01

    Recent publications estimate the prevalence of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) exceeds 50%, and this rate is likely higher among older patients. Cognitive impairment may impact medication adherence, and symptomatic impairment has been linked to all-cause mortality providing some impetus for early detection. There are currently insufficient data to inform solid recommendations on screening methods. Most HIV-specific tools have poor performance characteristics for all but the most severe form of impairment, which accounts for <5% of cases. Reliance on symptoms is likely to miss a substantial proportion of individuals with HAND due to poor insight, confounding mood disturbances, and lack of well-informed proxies. In the aging HIV-positive population, broader screening tools may be required to allow sensitivity for both HIV and neurodegenerative disorders. We describe the clinical presentation of HAND, review existing data related to screening tools, and provide preliminary and practical recommendations in the absence of more definitive studies. PMID:21921226

  2. Human Immunodeficiency Syndromes Affecting Human Natural Killer Cell Cytolytic Activity

    PubMed Central

    Ham, Hyoungjun; Billadeau, Daniel D.

    2013-01-01

    Natural killer (NK) cells are lymphocytes of the innate immune system that secrete cytokines upon activation and mediate the killing of tumor cells and virus-infected cells, especially those that escape the adaptive T cell response caused by the down regulation of MHC-I. The induction of cytotoxicity requires that NK cells contact target cells through adhesion receptors, and initiate activation signaling leading to increased adhesion and accumulation of F-actin at the NK cell cytotoxic synapse. Concurrently, lytic granules undergo minus-end directed movement and accumulate at the microtubule-organizing center through the interaction with microtubule motor proteins, followed by polarization of the lethal cargo toward the target cell. Ultimately, myosin-dependent movement of the lytic granules toward the NK cell plasma membrane through F-actin channels, along with soluble N-ethylmaleimide-sensitive factor attachment protein receptor-dependent fusion, promotes the release of the lytic granule contents into the cleft between the NK cell and target cell resulting in target cell killing. Herein, we will discuss several disease-causing mutations in primary immunodeficiency syndromes and how they impact NK cell-mediated killing by disrupting distinct steps of this tightly regulated process. PMID:24478771

  3. Hypogonadism in Human Immunodeficiency Virus-Positive Men

    PubMed Central

    Goldmeier, David; Sadeghi-Nejad, Hossein

    2014-01-01

    In recent years, the life expectancy for those living with human immunodeficiency virus (HIV) with access to combined antiretroviral therapy (cART) has increased. As men live longer, the role testosterone plays in sexual function as well as in general well-being is becoming increasingly important. Here we discuss the available literature concerning androgens and HIV disease. A review was undertaken by using a PubMed search with the umbrella terms HIV or AIDS and testosterone or androgens spanning 1985 to 2011. Significant articles found in references in the primary search were also included. The reported prevalence of androgen deficiency appears to be greater in HIV-infected males than in the general population. Androgen deficiency is usually associated with low luteinizing hormone and follicle-stimulating hormone and is sensitive to the type of measurement of testosterone used. Rates of hypogonadism may be falling since the advent of cART. Causes of low testosterone levels have been attributed to chronic illness, HIV replication, cART, opportunistic infections, comorbidities and coinfections, wasting, and normal age-related declines. Studies of testosterone treatment in HIV-positive men are lacking in standardization and outcome measures. PMID:24466391

  4. Human immunodeficiency virus type 1 infection of the brain.

    PubMed Central

    Atwood, W J; Berger, J R; Kaderman, R; Tornatore, C S; Major, E O

    1993-01-01

    Direct infection of the central nervous system by human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS, was not appreciated in the early years of the AIDS epidemic. Neurological complications associated with AIDS were largely attributed to opportunistic infections that arose as a result of the immunocompromised state of the patient and to depression. In 1985, several groups succeeded in isolating HIV-1 directly from brain tissue. Also that year, the viral genome was completely sequenced, and HIV-1 was found to belong to a neurotropic subfamily of retrovirus known as the Lentivirinae. These findings clearly indicated that direct HIV-1 infection of the central nervous system played a role in the development of AIDS-related neurological disease. This review summarizes the clinical manifestations of HIV-1 infection of the central nervous system and the related neuropathology, the tropism of HIV-1 for specific cell types both within and outside of the nervous system, the possible mechanisms by which HIV-1 damages the nervous system, and the current strategies for diagnosis and treatment of HIV-1-associated neuropathology. Images PMID:8269391

  5. Human Immunodeficiency Virus Type 1 Infection of Neural Xenografts

    NASA Astrophysics Data System (ADS)

    Cvetkovich, Therese A.; Lazar, Eliot; Blumberg, Benjamin M.; Saito, Yoshihiro; Eskin, Thomas A.; Reichman, Richard; Baram, David A.; del Cerro, Coca; Gendelman, Howard E.; del Cerro, Manuel; Epstein, Leon G.

    1992-06-01

    Human immunodeficiency virus type 1 (HIV-1) infection is highly specific for its human host. To study HIV-1 infection of the human nervous system, we have established a small animal model in which second-trimester (11 to 17.5 weeks) human fetal brain or neural retina is transplanted to the anterior chamber of the eye of immunosuppressed adult rats. The human xenografts vascularized, formed a blood-brain barrier, and differentiated, forming neurons and glia. The xenografts were infected with cell-free HIV-1 or with HIV-1-infected human monocytes. Analysis by polymerase chain reaction revealed HIV-1 sequences in DNA from xenograft tissue exposed to HIV-1 virions, and in situ hybridization demonstrated HIV-1 mRNA localized in macrophages and multinucleated giant cells. Pathological damage was observed only in neural xenografts containing HIV-1-infected human monocytes, supporting the hypothesis that these cells mediate neurotoxicity. This small animal model allows the study of direct and indirect effects of HIV-1 infection on developing human fetal neural tissues, and it should prove useful in evaluating antiviral therapies, which must ultimately target HIV-1 infection of the brain.

  6. Markers predicting progression of human immunodeficiency virus-related disease.

    PubMed Central

    Tsoukas, C M; Bernard, N F

    1994-01-01

    Human immunodeficiency virus (HIV) interacts with the immune system throughout the course of infection. For most of the disease process, HIV activates the immune system, and the degree of activation can be assessed by measuring serum levels of molecules such as beta 2-microglobulin and neopterin, as well as other serum and cell surface phenotype markers. The levels of some of these markers correlate with clinical progression of HIV disease, and these markers may be useful as surrogate markers for development of clinical AIDS. Because the likelihood and timing of development of clinical AIDS following seroconversion, for any particular individual, are not readily predictable, the use of nonclinical disease markers has become critically important to patient management. Surrogate markers of HIV infection are, by definition, measurable traits that correlate with disease progression. An ideal marker should identify patients at highest risk of disease progression, provide information on how long an individual has been infected, help in staging HIV disease, predict development of opportunistic infections associated with AIDS, monitor the therapeutic efficacy of immunomodulating or antiviral treatments, and the easily quantifiable, reliable, clinically available, and affordable. This review examines the current state of knowledge and the role of surrogate markers in the natural history and treatment of HIV infection. The clinical usefulness of each marker is assessed with respect to the criteria outlined for the ideal surrogate marker for HIV disease progression. PMID:8118788

  7. Outbreaks of Pneumocystis carinii pneumonia in colonies of immunodeficient mice.

    PubMed Central

    Walzer, P D; Kim, C K; Linke, M J; Pogue, C L; Huerkamp, M J; Chrisp, C E; Lerro, A V; Wixson, S K; Hall, E; Shultz, L D

    1989-01-01

    Outbreaks of Pneumocystis carinii pneumonia occurred in colonies of nu/nu and scid/scid mice at four different institutions. The disease, which was characterized by chronic wasting and respiratory insufficiency, was more severe in older mice and in animals housed in cages with special protective tops. Histopathologic features included alveolar filling with the typical foamy honeycomb material and a mild, nonspecific host inflammatory response. Immunofluorescence and immunoblotting studies suggested the P. carinii isolate was of mouse rather than of rat or human origin, and the outbreaks could be related to each other by common vendor or source of breeding animals. Once P. carinii became established in a mouse colony, the organism tended to persist for long periods of time. The principal control measure was depopulation of the colony, although limited experience with the administration of trimethoprim-sulfamethoxazole was encouraging. Thus, outbreaks of pneumocystosis are a serious problem among colonies of immunodeficient mice, with important implications for the use of these animals in biomedical research. Data obtained by studying these outbreaks should enhance understanding of the pathogenesis of P. carinii pneumonia and be helpful in formulating improved methods of detection and control. Images PMID:2642471

  8. Testicular dysfunction in human immunodeficiency virus-infected men.

    PubMed

    Poretsky, L; Can, S; Zumoff, B

    1995-07-01

    This review pertains to gonadal function in men with human immunodeficiency virus (HIV) infection, who often exhibit clinical and biochemical evidence of hypogonadism. Hypogonadotropic hypogonadism appears to be the most commonly encountered abnormality, although complete anterior pituitary insufficiency and primary gonadal failure have been reported. Levels of sex hormone-binding globulin (SHBG) are either unchanged or increased. Plasma levels of estrogens, progesterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), and prolactin vary. Pathologically, except for involvement by opportunistic infections, no significant abnormality in the hypothalamic-pituitary area has been described, but evidence of orchitis is commonly present. The cause(s) of these abnormalities remains unclear. The possible factors leading to hypogonadism in HIV-infected men include HIV infection itself, opportunistic infections, chronic debilitating illness, and effects of cytokines on the hypothalamic-pituitary-gonadal axis. Further studies are needed to clarify the cause(s) of testicular dysfunction in HIV-infected men and its clinical significance, treatment, relevance to the progression of HIV infection, and influence on the immune system. PMID:7616856

  9. Diagnostics of Primary Immunodeficiency Diseases: A Sequencing Capture Approach

    PubMed Central

    Moens, Lotte N.; Falk-Sörqvist, Elin; Asplund, A. Charlotta; Bernatowska, Ewa; Smith, C. I. Edvard; Nilsson, Mats

    2014-01-01

    Primary Immunodeficiencies (PID) are genetically inherited disorders characterized by defects of the immune system, leading to increased susceptibility to infection. Due to the variety of clinical symptoms and the complexity of current diagnostic procedures, accurate diagnosis of PID is often difficult in daily clinical practice. Thanks to the advent of “next generation” sequencing technologies and target enrichment methods, the development of multiplex diagnostic assays is now possible. In this study, we applied a selector-based target enrichment assay to detect disease-causing mutations in 179 known PID genes. The usefulness of this assay for molecular diagnosis of PID was investigated by sequencing DNA from 33 patients, 18 of which had at least one known causal mutation at the onset of the experiment. We were able to identify the disease causing mutations in 60% of the investigated patients, indicating that the majority of PID cases could be resolved using a targeted sequencing approach. Causal mutations identified in the unknown patient samples were located in STAT3, IGLL1, RNF168 and PGM3. Based on our results, we propose a stepwise approach for PID diagnostics, involving targeted resequencing, followed by whole transcriptome and/or whole genome sequencing if causative variants are not found in the targeted exons. PMID:25502423

  10. Genotypic Testing for Human Immunodeficiency Virus Type 1 Drug Resistance

    PubMed Central

    Shafer, Robert W.

    2002-01-01

    There are 16 approved human immunodeficiency virus type 1 (HIV-1) drugs belonging to three mechanistic classes: protease inhibitors, nucleoside and nucleotide reverse transcriptase (RT) inhibitors, and nonnucleoside RT inhibitors. HIV-1 resistance to these drugs is caused by mutations in the protease and RT enzymes, the molecular targets of these drugs. Drug resistance mutations arise most often in treated individuals, resulting from selective drug pressure in the presence of incompletely suppressed virus replication. HIV-1 isolates with drug resistance mutations, however, may also be transmitted to newly infected individuals. Three expert panels have recommended that HIV-1 protease and RT susceptibility testing should be used to help select HIV drug therapy. Although genotypic testing is more complex than typical antimicrobial susceptibility tests, there is a rich literature supporting the prognostic value of HIV-1 protease and RT mutations. This review describes the genetic mechanisms of HIV-1 drug resistance and summarizes published data linking individual RT and protease mutations to in vitro and in vivo resistance to the currently available HIV drugs. PMID:11932232

  11. Kunjin Virus Replicon Vectors for Human Immunodeficiency Virus Vaccine Development†

    PubMed Central

    Harvey, Tracey J.; Anraku, Itaru; Linedale, Richard; Harrich, David; Mackenzie, Jason; Suhrbier, Andreas; Khromykh, Alexander A.

    2003-01-01

    We have previously demonstrated the ability of the vaccine vectors based on replicon RNA of the Australian flavivirus Kunjin (KUN) to induce protective antiviral and anticancer CD8+ T-cell responses using murine polyepitope as a model immunogen (I. Anraku, T. J. Harvey, R. Linedale, J. Gardner, D. Harrich, A. Suhrbier, and A. A. Khromykh, J. Virol. 76:3791-3799, 2002). Here we showed that immunization of BALB/c mice with KUN replicons encoding HIV-1 Gag antigen resulted in induction of both Gag-specific antibody and protective Gag-specific CD8+ T-cell responses. Two immunizations with KUNgag replicons in the form of virus-like particles (VLPs) induced anti-Gag antibodies with titers of ?1:10,000. Immunization with KUNgag replicons delivered as plasmid DNA, naked RNA, or VLPs induced potent Gag-specific CD8+ T-cell responses, with one immunization of KUNgag VLPs inducing 4.5-fold-more CD8+ T cells than the number induced after immunization with recombinant vaccinia virus carrying the gag gene (rVVgag). Two immunizations with KUNgag VLPs also provided significant protection against challenge with rVVgag. Importantly, KUN replicon VLP vaccinations induced long-lasting immune responses with CD8+ T cells able to secrete gamma interferon and to mediate protection 6 to 10 months after immunization. These results illustrate the potential value of the KUN replicon vectors for human immunodeficiency virus vaccine design. PMID:12829819

  12. Severe combined immunodeficiency: recent developments and guidance on clinical management.

    PubMed

    Rivers, Lizzy; Gaspar, H Bobby

    2015-07-01

    Severe combined immunodeficiency (SCID) is a rare but important condition. Affected infants are born with profound abnormalities of immune cell function that lead to severe and recurrent infection that are almost always fatal in the first year of life without treatment. Infants with SCID are often initially seen by general paediatricians in the hospital care setting, and the recognition of the cardinal features of the disease and alertness to specific laboratory parameters are important in making an early diagnosis. There is also increasing interest in newborn screening for SCID, which has the potential to significantly improve outcome through early diagnosis and implementation of prophylactic medications. Definitive treatments such as haematopoietic stem cell transplantation and gene therapy have also made major advances over the last decade and again promise to improve the overall outcome for SCID with reduced long-term toxicities. In this review, we highlight some of the major advances in diagnosis and management of the disease, but we also want to emphasise the important role of the general paediatrician in making an early diagnosis and in ongoing management. PMID:25564533

  13. Natural simian immunodeficiency virus transmission in mandrills: a family affair?

    PubMed Central

    Fouchet, David; Verrier, Delphine; Ngoubangoye, Barthélémy; Souquière, Sandrine; Makuwa, Maria; Kazanji, Mirdad; Gonzalez, Jean-Paul; Pontier, Dominique

    2012-01-01

    Understanding how pathogens spread and persist in the ecosystem is critical for deciphering the epidemiology of diseases of significance for global health and the fundamental mechanisms involved in the evolution of virulence and host resistance. Combining long-term behavioural and epidemiological data collected in a naturally infected mandrill population and a Bayesian framework, the present study investigated unknown aspects of the eco-epidemiology of simian immunodeficiency virus (SIV), the recent ancestor of HIV. Results show that, in contrast to what is expected from aggressive and sexual transmission (i.e. the two commonly accepted transmission modes for SIV), cases of SIVmnd-1 subtype were significantly correlated among related individuals (greater than 30% of the observed cases). Challenging the traditional view of SIV, this finding suggests the inheritance of genetic determinants of susceptibility to SIV and/or a role for behavioural interactions among maternal kin affecting the transmission of the virus, which would highlight the underappreciated role of sociality in the spread of infectious diseases. Outcomes of this study also provide novel insights into the role of host social structure in the evolution of pathogens. PMID:22673358

  14. Escape of human immunodeficiency virus from immune control.

    PubMed

    McMichael, A J; Phillips, R E

    1997-01-01

    Cytotoxic T lymphocytes (CTL) play a crucial role in the attempt to control infection with human immunodeficiency virus (HIV). Variation in epitopes recognized by CTL is common and frequently offers potential escape routes for mutant virus. Proof of escape, however, requires demonstration of increased frequency of virus particles or provirus that carry the escape sequence. There are now several recorded examples of virus variants that escape from CTL and are then selected. Most dramatic are those in which the CTL response has been dominated by CTL recognizing a single epitope that has suddenly changed, resulting in escape to fixation. This has been seen both early and late in the infection, leaving no doubt that escape occurs. Such escape is likely to be favored when the antiviral CTL response is oligoclonal and focused on a small number of immunodominant epitopes. The heterogeneous CTL response seen in many HIV-infected patients may result from successive waves of virus escape followed by new CTL responses specific for subdominant epitopes. Mutant virus can escape by several different routes, including failure of the mutated peptide to bind to the presenting HLA molecule and altered interactions with T cell receptors (TCR), including antagonism. PMID:9143689

  15. Novel inhibitors of human immunodeficiency virus type 2 infectivity.

    PubMed

    Beach, Lauren B; Rawson, Jonathan M; Kim, Baek; Patterson, Steven E; Mansky, Louis M

    2014-12-01

    Human immunodeficiency virus type 2 (HIV-2) infects about two million people worldwide. HIV-2 has fewer treatment options than HIV-1, yet may evolve drug resistance more quickly. We have analysed several novel drugs for anti-HIV-2 activity. It was observed that 5-azacytidine, clofarabine, gemcitabine and resveratrol have potent anti-HIV-2 activity. The EC50 values for 5-azacytidine, clofarabine and resveratrol were found to be significantly lower with HIV-2 than with HIV-1. A time-of-addition assay was used to analyse the ability of these drugs to interfere with HIV-2 replication. Reverse transcription was the likely target for antiretroviral activity. Taken together, several novel drugs have been discovered to have activity against HIV-2. Based upon their known activities, these drugs may elicit enhanced HIV-2 mutagenesis and therefore be useful for inducing HIV-2 lethal mutagenesis. In addition, the data are consistent with HIV-2 reverse transcriptase being more sensitive than HIV-1 reverse transcriptase to dNTP pool alterations. PMID:25103850

  16. Natural simian immunodeficiency virus transmission in mandrills: a family affair?

    PubMed

    Fouchet, David; Verrier, Delphine; Ngoubangoye, Barthélémy; Souquière, Sandrine; Makuwa, Maria; Kazanji, Mirdad; Gonzalez, Jean-Paul; Pontier, Dominique

    2012-09-01

    Understanding how pathogens spread and persist in the ecosystem is critical for deciphering the epidemiology of diseases of significance for global health and the fundamental mechanisms involved in the evolution of virulence and host resistance. Combining long-term behavioural and epidemiological data collected in a naturally infected mandrill population and a Bayesian framework, the present study investigated unknown aspects of the eco-epidemiology of simian immunodeficiency virus (SIV), the recent ancestor of HIV. Results show that, in contrast to what is expected from aggressive and sexual transmission (i.e. the two commonly accepted transmission modes for SIV), cases of SIVmnd-1 subtype were significantly correlated among related individuals (greater than 30% of the observed cases). Challenging the traditional view of SIV, this finding suggests the inheritance of genetic determinants of susceptibility to SIV and/or a role for behavioural interactions among maternal kin affecting the transmission of the virus, which would highlight the underappreciated role of sociality in the spread of infectious diseases. Outcomes of this study also provide novel insights into the role of host social structure in the evolution of pathogens. PMID:22673358

  17. Hepatitis B and human immunodeficiency virus co-infection.

    PubMed

    Phung, Bao-Chau; Sogni, Philippe; Launay, Odile

    2014-12-14

    Hepatitis B and human immunodeficiency virus (HBV and HIV) infection share transmission patterns and risk factors, which explains high prevalence of chronic HBV infection in HIV infected patients. The natural course of HBV disease is altered by the HIV infection with less chance to clear acute HBV infection, faster progression to cirrhosis and higher risk of liver-related death in HIV-HBV co-infected patients than in HBV mono-infected ones. HIV infected patients with chronic hepatitis B should be counseled for liver damage and surveillance of chronic hepatitis B should be performed to screen early hepatocellular carcinoma. Noninvasive tools are now available to evaluate liver fibrosis. Isolated hepatitis B core antibodies (anti-HBc) are a good predictive marker of occult HBV infection. Still the prevalence and significance of occult HBV infection is controversial, but its screening may be important in the management of antiretroviral therapy. Vaccination against HBV infection is recommended in non-immune HIV patients. The optimal treatment for almost all HIV-HBV co-infected patients should contain tenofovir plus lamivudine or emtricitabine and treatment should not be stopped to avoid HBV reactivation. Long term tenofovir therapy may lead to significant decline in hepatitis B surface Antigen. The emergence of resistant HBV strains may compromise the HBV therapy and vaccine therapy. PMID:25516647

  18. [Lung infections in acquired immunodeficiency. Clinico-radiologic correlations].

    PubMed

    Cecconi, L; Busi Rizzi, E; Mazzuoli, G; Schininà, V

    1994-05-01

    Over the last decade the number of subjects with acquired immunodeficiencies has markedly increased; this phenomenon depends on both the large number of patients receiving organ transplants or antiblastic therapy and the spread of infections caused by the HIV virus. In 70-90% of these patients primary diseases include different pulmonary infections, relative to the type and degree of immune compromission. Pathogenic or, in most cases, opportunistic germs are responsible for severe pneumonia whose mortality rate can top 50%. Since prognosis depends on the promptness of treatment, the diagnosis of nature must be made quickly by integrating clinical and diagnostic findings with laboratory and instrumental results. Conventional chest radiology plays a major role as the first step in a diagnostic iter which can now include rather sensitive techniques--e.g., equalized chest films. CT and nuclear medicine often represent the necessary diagnostic complements but, in some cases, etiology can be diagnosed only with such invasive procedures as lung biopsy. The authors reviewed the current data on the diagnostic imaging findings of pulmonary infections caused by common germs, by Pneumocystis carinii mycobacteria, mycetes and viruses in immunocompromised patients, integrating their personal experience with literature data. PMID:8209024

  19. The status of neutral currents

    SciTech Connect

    Zwirner, F.

    1987-11-01

    The situation of particle physics today is quite puzzling. On the one hand, the Standard Model (SM) of strong and electroweak interactions is consistent with all confirmed experimental data but theoretically rather unsatisfactory. On the other hand, none of the many theoretical speculations which try to go beyond the SM has (yet) received the slightest experimental support. The solution to this dilemma can only come from new data: either from the detection of a new particle threshold at high energy colliders, or from the appearance of some small discrepancy in high-precision experiments. A crucial sector for testing the SM and its extensions is that of neutral currents (NC), where an impressive amount of data has been collected in recent years. While waiting for the next generation of experiments, it is certainly useful to take stock of our knowledge, determining the NC parameters as precisely as we can and putting limits on possible deviations from the SM. The present talk contains the results of a recent analysis along these lines: the first part illustrates how a set of 'model-independent' parameters can be extracted from the available NC data, the second part particularizes the analysis to the SM and to some superstring-inspired models with an additional Z' in their low-energy spectrum. 27 refs., 3 figs., 1 tab.

  20. Neutral Models of Microbiome Evolution

    PubMed Central

    Zeng, Qinglong; Sukumaran, Jeet; Wu, Steven; Rodrigo, Allen

    2015-01-01

    There has been an explosion of research on host-associated microbial communities (i.e.,microbiomes). Much of this research has focused on surveys of microbial diversities across a variety of host species, including humans, with a view to understanding how these microbiomes are distributed across space and time, and how they correlate with host health, disease, phenotype, physiology and ecology. Fewer studies have focused on how these microbiomes may have evolved. In this paper, we develop an agent-based framework to study the dynamics of microbiome evolution. Our framework incorporates neutral models of how hosts acquire their microbiomes, and how the environmental microbial community that is available to the hosts is assembled. Most importantly, our framework also incorporates a Wright-Fisher genealogical model of hosts, so that the dynamics of microbiome evolution is studied on an evolutionary timescale. Our results indicate that the extent of parental contribution to microbial availability from one generation to the next significantly impacts the diversity of microbiomes: the greater the parental contribution, the less diverse the microbiomes. In contrast, even when there is only a very small contribution from a constant environmental pool, microbial communities can remain highly diverse. Finally, we show that our models may be used to construct hypotheses about the types of processes that operate to assemble microbiomes over evolutionary time. PMID:26200800

  1. Affinity maturation in an HIV broadly neutralizing B-cell lineage through reorientation of variable domains

    PubMed Central

    Fera, Daniela; Schmidt, Aaron G.; Haynes, Barton F.; Gao, Feng; Liao, Hua-Xin; Kepler, Thomas B.; Harrison, Stephen C.

    2014-01-01

    Rapidly evolving pathogens, such as human immunodeficiency and influenza viruses, escape immune defenses provided by most vaccine-induced antibodies. Proposed strategies to elicit broadly neutralizing antibodies require a deeper understanding of antibody affinity maturation and evolution of the immune response to vaccination or infection. In HIV-infected individuals, viruses and B cells evolve together, creating a virus?antibody “arms race.” Analysis of samples from an individual designated CH505 has illustrated the interplay between an antibody lineage, CH103, and autologous viruses at various time points. The CH103 antibodies, relatively broad in their neutralization spectrum, interact with the CD4 binding site of gp120, with a contact dominated by CDRH3. We show by analyzing structures of progenitor and intermediate antibodies and by correlating them with measurements of binding to various gp120s that there was a shift in the relative orientation of the light- and heavy-chain variable domains during evolution of the CH103 lineage. We further show that mutations leading to this conformational shift probably occurred in response to insertions in variable loop 5 (V5) of the HIV envelope. The shift displaced the tips of the light chain away from contact with V5, making room for the inserted residues, which had allowed escape from neutralization by the progenitor antibody. These results, which document the selective mechanism underlying this example of a virus?antibody arms race, illustrate the functional significance of affinity maturation by mutation outside the complementarity determining region surface of the antibody molecule. PMID:24982157

  2. Giant magnetodrag in graphene at charge neutrality.

    PubMed

    Titov, M; Gorbachev, R V; Narozhny, B N; Tudorovskiy, T; Schütt, M; Ostrovsky, P M; Gornyi, I V; Mirlin, A D; Katsnelson, M I; Novoselov, K S; Geim, A K; Ponomarenko, L A

    2013-10-18

    We report experimental data and theoretical analysis of Coulomb drag between two closely positioned graphene monolayers in a weak magnetic field. Close enough to the neutrality point, the coexistence of electrons and holes in each layer leads to a dramatic increase of the drag resistivity. Away from charge neutrality, we observe nonzero Hall drag. The observed phenomena are explained by decoupling of electric and quasiparticle currents which are orthogonal at charge neutrality. The sign of magnetodrag depends on the energy relaxation rate and geometry of the sample. PMID:24182287

  3. Human immunodeficiency virus postexposure prophylaxis for adolescents and children.

    PubMed

    Merchant, R C; Keshavarz, R

    2001-08-01

    Children and adolescents are at risk for human immunodeficiency virus (HIV) infection. Transmission occurs through perinatal exposures, injecting drug use, consensual and nonconsensual sex, needle-stick and sharp injuries, and possibly some unusual contacts. Youth engaging in high-risk sexual activities are especially endangered. Half of the estimated worldwide 5.3 million new HIV infections occur in adolescents and young adults aged 15 to 24. Of 20 000 known new adult and adolescent cases in the United States, 25% involve 13- to 21-year-olds. More than 1.4 million children worldwide (aged 15 and younger) are believed to be infected, and >1640 new cases are diagnosed daily. Of the 432 000 people reported to be living with HIV or acquired immunodeficiency syndrome (AIDS) in the United States, 5575 are children under 13. HIV postexposure prophylaxis (PEP) is a form of secondary HIV prevention that may reduce the incidence of HIV infections. HIV PEP is commonly conceived of as 2 types: occupational and nonoccupational. Occupational HIV PEP is an accepted form of therapy for health care workers exposed to HIV through their jobs. A landmark study of healthcare workers concluded that occupational HIV PEP may be efficacious. Well-established US national guidelines for occupational HIV PEP exist for this at-risk population. Nonoccupational HIV PEP includes all other forms of HIV PEP, such as that given after sexual assault and consensual sex, injecting drug use, and needle-stick and sharp injuries in non-health care persons. Pediatric HIV PEP is typically the nonoccupational type. The efficacy of nonoccupational HIV PEP is unknown. The presumed efficacy is based on a collection of animal and human data concerning occupational, perinatal, and nonoccupational exposures to HIV. In contrast to occupational HIV PEP, there are no national US guidelines for nonoccupational HIV PEP, and few recommendations are available for its use for adolescents and children. Regardless of this absence, there is encouraging evidence supporting the value of HIV PEP in its various forms in pediatrics. Although unproven, the presumed mechanism for HIV PEP comes from animal and human work suggesting that shortly after an exposure to HIV, a window period exists during which the viral load is small enough to be controlled by the body's immune system. Antiretroviral medications given during this period may help to diminish or end viral replication, thereby reducing the viral inoculum to a more potentially manageable target for the host's defenses. HIV PEP is accepted practice in the perinatal setting and for health care workers with occupational injuries. The medical literature supports prescribing HIV PEP after community needle-stick and sharp injuries and after sexual assault from sources known or likely to be HIV-infected. HIV PEP after consensual unprotected intercourse between HIV sero-opposite partners has had growing use in the adult population, and can probably be utilized for children and adolescents. There is less documented experience and support for HIV PEP after consensual unprotected intercourse between partners of unknown HIV status, after prolonged or multiple episodes of sexual abuse from an assailant of unknown HIV status, after bites, and after the sharing of personal hygiene items or exposure to wounds of HIV-infected individuals. There are no formal guidelines for HIV PEP in adolescents and children. A few groups have commented on its provision in pediatrics, and some preliminary studies have been released. Our article provides a discussion of the data available on HIV transmission and HIV PEP in pediatrics. In our article, we propose an HIV PEP approach for adolescents and children. We recommend a stratified regimen, based on the work of Gerberding and Katz and other authors, that attempts to match seroconversion risk with an appropriate number of medications, while taking into account adverse side-effects and the amount of information that is typically available upon initial presentation. Twice daily regimens should be used when pos

  4. Special Issues Involving Periprosthetic Infection in Immunodeficiency Patients

    PubMed Central

    Tornero, Eduard; Riba, Josep; Garcia-Ramiro, Sebastian

    2013-01-01

    Chronic systemic illnesses such as diabetes mellitus, chronic kidney disease (CKD), liver cirrhosis, neoplasia, etc. have been clearly associated with high rates of SWI. However, the exact mechanisms underlying these observations are still under investigation. Chronic kidney disease (CKD) is a growing problem in our society. Many of these patients will require an arthroplasty and it appears that the prosthetic infection risk for these types of patients is much higher than in the normal population. The risk of complications due to infection seems to be lower in patients with kidney transplants than in patients undergoing haemodialysis. Both prophylaxis and treatment of infection in patients with CKD should be carried out with a strict monitoring of potentially nephrotoxic antibiotics. The literature on the prognosis and risk of infection in patients with haematopoietic stem cell transplant is scarce and occasionally contradictory. The optimal time for the surgery should be determined by taking into account the immunological state of the patient and should be avoided, as much as possible, during the first year after the HSCT. Child’s classification system is the most widely used method of stratifying the surgical risk for patients with cirrhosis; the infection appeared to be associated in a statistically significant way with advanced age and a Child B pre-operative classification. The prevention of prosthetic joint infections in HIV-infected patients should not be significantly different from the prevention for any other patient. Those patients that receive adequate antiretroviral treatment and periodic laboratory control show infection rates and periprosthetic complications that are similar to those for patients not affected by HIV. Therefore, the patient’s level of immunodeficiency is the most important prognostic factor for prosthetic infection. The particular immunological condition of these patients can lead to infections due to particular microorganisms that immunocompetent patients do not have to deal with. Of all possibilities, because of their frequency and difficulty to treat, infections caused by methicillin-resistant S. aureus and fungus are highlighted. PMID:23919096

  5. Pathogenesis of simian immunodeficiency virus encephalitis: viral determinants of neurovirulence.

    PubMed Central

    Mankowski, J L; Flaherty, M T; Spelman, J P; Hauer, D A; Didier, P J; Amedee, A M; Murphey-Corb, M; Kirstein, L M; Muñoz, A; Clements, J E; Zink, M C

    1997-01-01

    To examine the relationship between macrophage tropism and neurovirulence, macaques were inoculated with two recombinant hybrid viruses derived from the parent viruses SIVmac239, a lymphocyte-tropic, non-neurovirulent clone, and SIV/17E-Br, a macrophage-tropic, neurovirulent virus strain. The first recombinant, SIV/17E-Cl, contained the portion of the env gene that encodes the surface glycoprotein and a short segment of the transmembrane glycoprotein of SIV/17E-Br in the backbone of SIVmac239. Unlike SIVmac239, SIV/17E-Cl replicated productively in macrophages, demonstrating that sequences in the surface portion of env determine macrophage tropism. None of five macaques inoculated with SIV/17E-Cl developed simian immunodeficiency virus (SIV) encephalitis. The second recombinant, SIV/17E-Fr, which contained the entire env and nef genes and the 3' long terminal repeat of SIV/17E-Br in the SIVmac239 backbone, was also macrophage tropic. Six of nine macaques inoculated with SIV/17E-Fr developed SIV encephalitis ranging from mild to moderate in severity, indicating a significant (P = 0.031) difference in the neurovirulence of the two recombinants. In both groups of macaques, CD4+ cell counts declined gradually during infection and there was no significant difference in the rate of the decline between the two groups of macaques. This study demonstrated that macrophage tropism alone is not sufficient for the development of neurological disease. In addition, it showed that while sequences in the surface portion of the envelope gene determine macrophage tropism, additional sequences derived from the transmembrane portion of envelope and/or nef confer neurovirulence. PMID:9223498

  6. Leishmania and human immunodeficiency virus coinfection: the first 10 years.

    PubMed Central

    Alvar, J; Cañavate, C; Gutiérrez-Solar, B; Jiménez, M; Laguna, F; López-Vélez, R; Molina, R; Moreno, J

    1997-01-01

    Over 850 Leishmania-human immunodeficiency virus (HIV) coinfection cases have been recorded, the majority in Europe, where 7 to 17% of HIV-positive individuals with fever have amastigotes, suggesting that Leishmania-infected individuals without symptoms will express symptoms of leishmaniasis if they become immunosuppressed. However, there are indirect reasons and statistical data demonstrating that intravenous drug addiction plays a specific role in Leishmania infantum transmission: an anthroponotic cycle complementary to the zoonotic one has been suggested. Due to anergy in patients with coinfection, L. infantum dermotropic zymodemes are isolated from patient viscera and a higher L. infantum phenotypic variability is seen. Moreover, insect trypanosomatids that are currently considered nonpathogenic have been isolated from coinfected patients. HIV infection and Leishmania infection each induce important analogous immunological changes whose effects are multiplied if they occur concomitantly, such as a Th1-to-Th2 response switch; however, the consequences of the viral infection predominate. In fact, a large proportion of coinfected patients have no detectable anti-Leishmania antibodies. The microorganisms share target cells, and it has been demonstrated in vitro how L. infantum induces the expression of latent HIV-1. Bone marrow culture is the most useful diagnostic technique, but it is invasive. Blood smears and culture are good alternatives. PCR, xenodiagnosis, and circulating-antigen detection are available only in specialized laboratories. The relationship with low levels of CD4+ cells conditions the clinical presentation and evolution of disease. Most patients have visceral leishmaniasis, but asymptomatic, cutaneous, mucocutaneous, diffuse cutaneous, and post-kala-azar dermal leishmaniasis can be produced by L. infantum. The digestive and respiratory tracts are frequently parasitized. The course of coinfection is marked by a high relapse rate. There is a lack of randomized prospective treatment trials; therefore, coinfected patients are treated by conventional regimens. Prophylactic therapy is suggested to be helpful in preventing relapses. PMID:9105756

  7. Ensuring accurate testing for human immunodeficiency virus in Myanmar

    PubMed Central

    Kyaw, Latt Latt; Wada, Koji; Oo, Khin Yi; Tin, Htay Htay; Yoshihara, Namiko

    2015-01-01

    Abstract Problem Until 2005, the quality of rapid diagnostic human immunodeficiency virus (HIV) testing was not monitored and no regular technical support was provided to hospital laboratories in Myanmar. Approach The national reference laboratory introduced a national external quality assessment scheme. The scheme involved (i) training laboratory technicians in HIV testing and in the requirements of the quality assessment system; (ii) implementing a biannual proficiency panel testing programme; (iii) on-site assessments of poorly-performing laboratories to improve testing procedures; and (iv) development of national guidelines. Local setting In 2011, a total of 422 public hospitals in Myanmar had laboratories providing HIV tests. In addition, private laboratories supported by nongovernmental organizations (NGOs) conducted HIV testing. Relevant changes The scheme was started in 65 public laboratories in 2005. In 2012, it had expanded nationwide to 347 laboratories, including 33 NGO laboratories. During the expansion of the scheme, laboratory response rates were greater than 90% and the proportion of laboratories reporting at least one aberrant result improved from 9.2% (6/65) in 2005 to 5.4% (17/316) in 2012. Lessons learnt National testing guidelines and a reference laboratory are needed to successfully implement quality assurance of HIV testing services. On-site assessments are crucial for all participating laboratories and the only source for insight on the causes of aberrant results; lessons that the reference laboratory can share nationally. Proficiency testing helps laboratory technicians to maintain HIV testing skills by ensuring that they regularly encountered HIV-positive samples. PMID:25558106

  8. Optimism, coping, psychological distress, and high-risk sexual behavior among men at risk for acquired immunodeficiency syndrome (AIDS)

    Microsoft Academic Search

    Shelley E. Taylor; Margaret E. Kemeny; Lisa G. Aspinwall; Stephen G. Schneider

    1992-01-01

    In a cohort of gay men responding to the threat of acquired immunodeficiency syndrome (AIDS), dispositional optimism was associated with less distress, less avoidant coping, positive attitudes as a coping strategy, and fewer AIDS-related concerns. Men who knew they were seropositive for human immunodeficiency virus (HIV) were significantly more optimistic about not developing AIDS than men who knew they were

  9. Iatrogenic colorectal Kaposi sarcoma complicating a refractory ulcerative colitis in a human immunodeficiency negative-virus patient

    PubMed Central

    Hamzaoui, Lamine; Kilani, Houda; Bouassida, Mahdi; Mahmoudi, Moufida; Chalbi, Emna; Siai, Karima; Ezzine, Heykel; Touinsi, Hassen; Azzouz, Mohamed M'Saddak; Sassi, Sadok

    2013-01-01

    Kaposi sarcoma is a mesenchymal tumor associated to a human herpes virus-8. It often occurs in human immunodeficiency virus-positive subjects. Colorectal localization is rare. We report the case of a colorectal Kaposi sarcoma complicating a refractory ulcerative colitis treated with surgery after the failure of immunomodulator therapy in a human immunodeficiency virus-negative heterosexual man. PMID:24396560

  10. Iatrogenic colorectal Kaposi sarcoma complicating a refractory ulcerative colitis in a human immunodeficiency negative-virus patient.

    PubMed

    Hamzaoui, Lamine; Kilani, Houda; Bouassida, Mahdi; Mahmoudi, Moufida; Chalbi, Emna; Siai, Karima; Ezzine, Heykel; Touinsi, Hassen; Azzouz, Mohamed M'saddak; Sassi, Sadok

    2013-01-01

    Kaposi sarcoma is a mesenchymal tumor associated to a human herpes virus-8. It often occurs in human immunodeficiency virus-positive subjects. Colorectal localization is rare. We report the case of a colorectal Kaposi sarcoma complicating a refractory ulcerative colitis treated with surgery after the failure of immunomodulator therapy in a human immunodeficiency virus-negative heterosexual man. PMID:24396560

  11. Non-AIDS defining deaths and immunodeficiency in the era of combination antiretroviral therapy. CASCADE, 1996-2006.

    E-print Network

    Paris-Sud XI, Université de

    1 Title: Non-AIDS defining deaths and immunodeficiency in the era of combination antiretroviral therapy. CASCADE, 1996-2006. (102 characters) Running head: Non-AIDS causes of death and immunodeficiency Epidemiologia, Rome, Italy. inserm-00388946,version1-10Jan2012 Author manuscript, published in "AIDS 2009

  12. Viral Escape from Dominant Simian Immunodeficiency Virus Epitope-Specific Cytotoxic T Lymphocytes in DNA-Vaccinated Rhesus Monkeys

    Microsoft Academic Search

    Dan H. Barouch; Jennifer Kunstman; Jennifer Glowczwskie; Kevin J. Kunstman; Michael A. Egan; Fred W. Peyerl; Sampa Santra; Marcelo J. Kuroda; Jorn E. Schmitz; Kristin Beaudry; Georgia R. Krivulka; Michelle A. Lifton; Darci A. Gorgone; Steven M. Wolinsky; Norman L. Letvin

    2003-01-01

    Virus-specific cytotoxic T lymphocytes (CTL) are critical for control of human immunodeficiency virus type 1 replication. However, viral escape from CTL recognition can undermine this immune control. Here we dem- onstrate the high frequency and pattern of viral escape from dominant epitope-specific CTL in SIV gag DNA- vaccinated rhesus monkeys following a heterologous simian immunodeficiency virus (SIV) challenge. DNA- vaccinated

  13. Cytotoxic T Lymphocyte-based Control of Simian Immunodeficiency Virus Replication in a Preclinical AIDS Vaccine Trial

    Microsoft Academic Search

    Tetsuro Matano; Masahiro Kobayashi; Hiroko Igarashi; Akiko Takeda; Hiromi Nakamura; Munehide Kano; Chie Sugimoto; Kazuyasu Mori; Akihiro Iida; Takahiro Hirata; Mamoru Hasegawa; Takae Yuasa; Masaaki Miyazawa; Yumiko Takahashi; Michio Yasunami; Akinori Kimura; David H. O'Connor; David I. Watkins; Yoshiyuki Nagai

    2004-01-01

    Recently, encouraging AIDS vaccine trials in macaques have implicated cytotoxic T lympho- cytes (CTLs) in the control of the simian human immunodeficiency virus SHIV89.6P that induces acute CD4 ? T cell depletion. However, none of these vaccine regimens have been successful in the containment of replication of the pathogenic simian immunodeficiency viruses (SIVs) that induce chronic disease progression. Indeed, it

  14. The human immunodeficiency virus-reverse transcriptase inhibition activity of novel pyridine/pyridinium-type fullerene derivatives.

    PubMed

    Yasuno, Takumi; Ohe, Tomoyuki; Takahashi, Kyoko; Nakamura, Shigeo; Mashino, Tadahiko

    2015-08-15

    In the present study, we describe the synthesis of a novel set of pyridine/pyridinium-type fullerene derivatives. The products were assessed for human immunodeficiency virus-reverse transcriptase inhibition activities. All novel fullerene derivatives showed potent human immunodeficiency virus-reverse transcriptase inhibition without cytotoxicity. PMID:26081290

  15. Reduction of Simian-Human Immunodeficiency Virus 89.6P Viremia in Rhesus Monkeys by Recombinant Modified Vaccinia Virus Ankara Vaccination

    PubMed Central

    Barouch, Dan H.; Santra, Sampa; Kuroda, Marcelo J.; Schmitz, Jörn E.; Plishka, Ronald; Buckler-White, Alicia; Gaitan, Alicia E.; Zin, Rebekah; Nam, Jae-Hwan; Wyatt, Linda S.; Lifton, Michelle A.; Nickerson, Christine E.; Moss, Bernard; Montefiori, David C.; Hirsch, Vanessa M.; Letvin, Norman L.

    2001-01-01

    Since cytotoxic T lymphocytes (CTLs) are critical for controlling human immunodeficiency virus type 1 (HIV-1) replication in infected individuals, candidate HIV-1 vaccines should elicit virus-specific CTL responses. In this report, we study the immune responses elicited in rhesus monkeys by a recombinant poxvirus vaccine and the degree of protection afforded against a pathogenic simian-human immunodeficiency virus SHIV-89.6P challenge. Immunization with recombinant modified vaccinia virus Ankara (MVA) vectors expressing SIVmac239 gag-pol and HIV-1 89.6 env elicited potent Gag-specific CTL responses but no detectable SHIV-specific neutralizing antibody (NAb) responses. Following intravenous SHIV-89.6P challenge, sham-vaccinated monkeys developed low-frequency CTL responses, low-titer NAb responses, rapid loss of CD4+ T lymphocytes, high-setpoint viral RNA levels, and significant clinical disease progression and death in half of the animals by day 168 postchallenge. In contrast, the recombinant MVA-vaccinated monkeys demonstrated high-frequency secondary CTL responses, high-titer secondary SHIV-89.6-specific NAb responses, rapid emergence of SHIV-89.6P-specific NAb responses, partial preservation of CD4+ T lymphocytes, reduced setpoint viral RNA levels, and no evidence of clinical disease or mortality by day 168 postchallenge. There was a statistically significant correlation between levels of vaccine-elicited CTL responses prior to challenge and the control of viremia following challenge. These results demonstrate that immune responses elicited by live recombinant vectors, although unable to provide sterilizing immunity, can control viremia and prevent disease progression following a highly pathogenic AIDS virus challenge. PMID:11333896

  16. Lack of B Cell Dysfunction Is Associated with Functional, gp120-Dominant Antibody Responses in Breast Milk of Simian Immunodeficiency Virus-Infected African Green Monkeys

    PubMed Central

    Amos, Joshua D.; Wilks, Andrew B.; Fouda, Genevieve G.; Smith, Shannon D.; Colvin, Lisa; Mahlokozera, Tatenda; Ho, Carrie; Beck, Krista; Overman, R. Glenn; DeMarco, C. Todd; Hodge, Terry L.; LaBranche, Celia C.; Montefiori, David C.; Denny, Thomas N.; Liao, Hua-Xin; Tomaras, Georgia D.; Moody, M. Anthony

    2013-01-01

    The design of an effective vaccine to reduce the incidence of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) via breastfeeding will require identification of protective immune responses that block postnatal virus acquisition. Natural hosts of simian immunodeficiency virus (SIV) sustain nonpathogenic infection and rarely transmit the virus to their infants despite high milk virus RNA loads. This is in contrast to HIV-infected women and SIV-infected rhesus macaques (RhMs), nonnatural hosts which exhibit higher rates of postnatal virus transmission. In this study, we compared the systemic and mucosal B cell responses of lactating, SIV-infected African green monkeys (AGMs), a natural host species, to that of SIV-infected RhMs and HIV-infected women. AGMs did not demonstrate hypergammaglobulinemia or accumulate circulating memory B cells during chronic SIV infection. Moreover, the milk of SIV-infected AGMs contained higher proportions of naive B cells than RhMs. Interestingly, AGMs exhibited robust milk and plasma Env binding antibody responses that were one to two logs higher than those in RhMs and humans and demonstrated autologous neutralizing responses in milk at 1 year postinfection. Furthermore, the plasma and milk Env gp120-binding antibody responses were equivalent to or predominant over Env gp140-binding antibody responses in AGMs, in contrast to that in RhMs and humans. The strong gp120-specific, functional antibody responses in the milk of SIV-infected AGMs may contribute to the rarity of postnatal transmission observed in natural SIV hosts. PMID:23926338

  17. Safety of Attenuated Smallpox Vaccine LC16m8 in Immunodeficient Mice

    PubMed Central

    Shinmura, Yasuhiko; Kanehara, Tomomi; Maruno, Shinichi; Kuranaga, Masahiko; Matsui, Hajime; Hashizume, So

    2014-01-01

    Freeze-dried live attenuated smallpox vaccine LC16m8 prepared in cell culture has been the sole smallpox vaccine licensed in Japan since 1975 and was recently recommended as a WHO stockpile vaccine. We evaluated the safety of recently remanufactured lots of LC16m8 using a series of immunodeficient mouse models. These models included suckling mice, severe combined immunodeficiency disease (SCID) mice, and wild-type mice treated with cyclosporine. LC16m8 showed extremely low virulence in each of the three mouse models compared with that of its parental strains, Lister and LC16mO. These results provide further evidence that LC16m8 is one of the safest replication-competent smallpox vaccines in the world and may be considered for use in immunodeficient patients. PMID:24990910

  18. Recent key advances in human immunodeficiency virus medicine and implications for China.

    PubMed

    Sun, Kai; Zhou, Shuntai; Chen, Ray Y; Cohen, Myron S; Zhang, Fujie

    2010-01-01

    In this article we summarize several recent major developments in human immunodeficiency virus treatment, prevention, outcome, and social policy change. Updated international guidelines endorse more aggressive treatment strategies and safer antiretroviral drugs. New antiretroviral options are being tested. Important lessons were learned in the areas of human immunodeficiency virus vaccines and microbicide gels from clinical studies, and additional trials in prevention, especially pre-exposure prophylaxis, are nearing completion. Insight into the role of the virus in the pathogenesis of diseases traditionally thought to be unrelated to acquired immunodeficiency syndrome has become a driving force for earlier and universal therapy. Lastly, we review important achievements of and future challenges facing China as she steps into her eighth year of the National Free Antiretroviral Treatment Program. PMID:20500898

  19. Prevention of vaccinia virus infection in immunodeficient mice by vector-directed IL-2 expression.

    PubMed

    Flexner, C; Hügin, A; Moss, B

    Recombinant vaccinia viruses have been proposed as live vaccines against a variety of infectious diseases, including AIDS (acquired immune deficiency syndrome). Objections have been concerned primarily with side effects of the vaccinia virus vector itself. Recently it has been shown that inactivation of the vaccinia virus thymidine kinase gene or deletion of certain other non-essential genes is associated with a marked reduction in pathogenicity. Nevertheless, the ability of vaccinia virus to produce a progressive infection in immunodeficient individuals remains a most serious problem. Indeed, an incident of this type in a vaccinated man seropositive for human immunodeficiency virus was recently reported. We have used immunodeficient athymic nude mice to establish a model of disseminated vaccinia virus infection, and to demonstrate a novel approach to virus attenuation which involves insertion of a gene encoding human interleukin-2 into the genome of vaccinia virus vectors. PMID:3118219

  20. Immunodeficiency in a Child with Rapadilino Syndrome: A Case Report and Review of the Literature

    PubMed Central

    Vollebregt, M. M. G.; Malfroot, A.; De Raedemaecker, M.; van der Burg, M.; van der Werff ten Bosch, J. E.

    2015-01-01

    Rapadilino syndrome is a genetic disease characterized by a characteristic clinical tableau. It is caused by mutations in RECQL4 gene. Immunodeficiency is not described as a classical feature of the disease. We present a 2-year-old girl with Rapadilino syndrome with important lymphadenopathies and pneumonia due to disseminated Mycobacterium lentiflavum infection. An immunological work-up showed several unexpected abnormalities. Repeated blood samples showed severe lymphopenia. Immunophenotyping showed low T, B, and NK cells. No Treg cells were seen. T cell responses to stimulations were insufficient. The IL12/IL23 interferon gamma pathway was normal. Gamma globulin levels and vaccination responses were low. With this report, we aim to stress the importance of screening immunodeficiency in patients with RECQL4 mutations for immunodeficiency and the need to further research into its physiopathology.

  1. Culture-proved disseminated cat-scratch disease in acquired immunodeficiency syndrome.

    PubMed

    Schlossberg, D; Morad, Y; Krouse, T B; Wear, D J; English, C K; Littman, M

    1989-06-01

    A male homosexual (positive for the human immunodeficiency virus) with a recent cat scratch developed fever, epitrochlear and axillary lymphadenopathy, and retinitis. Subsequently, he developed skin (epitheloid hemangioma) and mucosal lesions (Kaposi's sarcoma), multiple liver abscesses, and pleural effusion. Warthin-Starry stains and/or electron micrographs of lymph nodes and skin lesions demonstrated bacilli characteristic of those associated with cat-scratch disease. Cultures of lymph node, pleural fluid, and liver abscess specimens yielded organisms believed to be the causative agent of cat-scratch disease. We believe that disseminated cat-scratch disease may become an indicator of opportunistic infection signaling acquired immunodeficiency syndrome in a patient who is positive for the human immunodeficiency virus. PMID:2730265

  2. Epidemiol. Infect. (1998), 121, 227236. Printed in the United Kingdom # 1998 Cambridge University Press At-risk individuals in Feline Immunodeficiency Virus

    E-print Network

    Courchamp, Franck

    1998-01-01

    Press At-risk individuals in Feline Immunodeficiency Virus epidemiology: evidence from a multivariate-54220 MalzeTville, France (Accepted 12 February 1998) SUMMARY Prevalence of Feline Immunodeficiency aggressive individuals, and the virus is endemic in this population. INTRODUCTION Feline Immunodeficiency

  3. Controllability of nonlinear neutral evolution integrodifferential systems

    Microsoft Academic Search

    R. Sakthivel; Q. H. Choi; S. M. Anthoni

    2002-01-01

    Sufficient conditions for controllability of nonlinear neutral evolution integrodifferential systems in a Banach space are established. The results are obtained by using the resolvent operators and the Schaefer fixed-point theorem. An application to partial integrodifferential equation is given.

  4. Solar Neutral Particles - Duration: 43 seconds.

    NASA Video Gallery

    This animation shows a neutral solar particle's path leaving the sun, following the magnetic field lines out to the heliosheath. The solar particle hits a hydrogen atom, stealing its electron, and ...

  5. Neutral Supersymmetric Higgs Boson Searches

    SciTech Connect

    Robinson, Stephen Luke; /Imperial Coll., London

    2009-09-01

    In some Supersymmetric extensions of the Standard Model, including the Minimal Supersymmetric Standard Model (MSSM), the coupling of Higgs bosons to b-quarks is enhanced. This enhancement makes the associated production of the Higgs with b-quarks an interesting search channel for the Higgs and Supersymmetry at D0. The identification of b-quarks, both online and offline, is essential to this search effort. This thesis describes the author's involvement in the development of both types of b-tagging and in the application of these techniques to the MSSM Higgs search. Work was carried out on the Level-3 trigger b-tagging algorithms. The impact parameter (IP) b-tagger was retuned and the effects of increased instantaneous luminosity on the tagger were studied. An extension of the IP-tagger to use the z-tracking information was developed. A new b-tagger using secondary vertices was developed and commissioned. A tool was developed to allow the use of large multi-run samples for trigger studies involving b-quarks. Offline, a neural network (NN) b-tagger was trained combining the existing offline lifetime based b-tagging tools. The efficiency and fake rate of the NN b-tagger were measured in data and MC. This b-tagger was internally reviewed and certified by the Collaboration and now provides the official b-tagging for all analyses using the Run IIa dataset at D0. A search was performed for neutral MSSM Higgs bosons decaying to a b{bar b} pair and produced in association with one or more b-quarks. Limits are set on the cross-section times the branching ratio for such a process. The limits were interpreted in various MSSM scenarios. This analysis uses the NN b-tagger and was the first to use this tool. The analysis also relies on triggers using the Level-3 IP b-tagging tool described previously. A likelihood discriminant was used to improve the analysis and a neural network was developed to cross-check this technique. The result of the analysis has been submitted to PRL and is comparable to the result from CDF in the same channel which uses approximately twice the integrated luminosity.

  6. Neutral thermospheric temperature from ion concentration measurements

    NASA Technical Reports Server (NTRS)

    Breig, E. L.; Donaldson, J. S.; Hanson, W. B.; Hoffman, J. H.; Power, R. A.; Kayser, D. C.; Spencer, N. W.; Wharton, L. E.

    1981-01-01

    A technique for extracting information on neutral temperature from in situ F region measurements of O(+) and H(+) ion concentrations is analyzed and evaluated. Advantage is taken of the condition of charge-exchange equilibrium of these species in the neighborhood of 320 km to infer the associated relative abundances of neutral oxygen and hydrogen. Results are shown to be generally consistent with other concurrent in situ measurements.

  7. A class of neutral functional differential equations.

    NASA Technical Reports Server (NTRS)

    Melvin, W. R.

    1972-01-01

    Formulation and study of the initial value problem for neutral functional differential equations. The existence, uniqueness, and continuation of solutions to this problem are investigated, and an analysis is made of the dependence of the solutions on the initial conditions and parameters, resulting in the derivation of a continuous dependence theorem in which the fundamental mathematical principles underlying the continuous dependence problem for a very general system of nonlinear neutral functional differential equations are separated out.

  8. Neutral-particle-beam production and injection

    SciTech Connect

    Post, D.; Pyle, R.

    1982-07-01

    This paper is divided into two sections: the first is a discussion of the interactions of neutral beams with confined plasmas, the second is concerned with the production and diagnosis of the neutral beams. In general we are dealing with atoms, molecules, and ions of the isotopes of hydrogen, but some heavier elements (for example, oxygen) will be mentioned. The emphasis will be on single-particle collisions; selected atomic processes on surfaces will be included.

  9. ITER neutral beam system US conceptual design

    SciTech Connect

    Purgalis, P.

    1990-09-01

    In this document we present the US conceptual design of a neutral beam system for International Thermonuclear Experimental Reactor (ITER). The design incorporates a barium surface conversion D{sup {minus}} source feeding a linear array of accelerator channels. The system uses a dc accelerator with electrostatic quadrupoles for strong focusing. A high voltage power supply that is integrated with the accelerator is presented as an attractive option. A gas neutralizer is used and residual ions exiting the neutralizer are deflected to water-cooled dumps. Cryopanels are located at the accelerator exit to pump excess gas from the source and the neutralizer, and in the ion dump cavity to pump re-neutralized ions and neutralizer gas. All the above components are packaged in compact identical, independent modules which can be removed for remote maintenance. The neutral beam system delivers 75 MW of DO at 1.3 MeV, into three ports with a total of 9 modules arranged in stacks of three modules per port . To increase reliability each module is designed to deliver up to 10 MW; this allows eight modules operating at partial capacity to deliver the required power in the event one module is out of service, and provides 20% excess capacity to improve availability. Radiation protection is provided by shielding and by locating critical components in the source and accelerator 46.5 m from the torus centerline. Neutron shielding in the drift duct and neutralizer provides the added feature of limiting conductance and thus reducing gas flow to and from the torus.

  10. Neutralizing Antibody Response to Hepatitis C Virus

    PubMed Central

    Wang, Yong; Keck, Zhen-Yong; Foung, Steven K. H.

    2011-01-01

    A critical first step in a “rational vaccine design” approach for hepatitis C virus (HCV) is to identify the most relevant mechanisms of immune protection. Emerging evidence provides support for a protective role of virus neutralizing antibodies, and the ability of the B cell response to modify the course of acute HCV infection. This has been made possible by the development of in vitro cell culture models, based on HCV retroviral pseudotype particles expressing E1E2 and infectious cell culture-derived HCV virions, and small animal models that are robust tools in studies of antibody-mediated virus neutralization. This review is focused on the immunogenic determinants on the E2 glycoprotein mediating virus neutralization and the pathways in which the virus is able to escape from immune containment. Encouraging findings from recent studies provide support for the existence of broadly neutralization antibodies that are not associated with virus escape. The identification of conserved epitopes mediating virus neutralization that are not associated with virus escape will facilitate the design of a vaccine immunogen capable of eliciting broadly neutralizing antibodies against this highly diverse virus. PMID:22163337

  11. Neutral particle kinetics in fusion devices

    SciTech Connect

    Tendler, M.; Heifetz, D.

    1986-05-01

    The theory of neutral particle kinetics treats the transport of mass, momentum, and energy in a plasma due to neutral particles which themselves are unaffected by magnetic fields. This transport affects the global power and particle balances in fusion devices, as well as profile control and plasma confinement quality, particle and energy fluxes onto device components, performance of pumping systems, and the design of diagnostics and the interpretation of their measurements. This paper reviews the development of analytic, numerical, and Monte Carlo methods of solving the time-independent Boltzmann equation describing neutral kinetics. These models for neutral particle behavior typically use adaptations of techniques developed originally for computing neutron transport, due to the analogy between the two phenomena, where charge-exchange corresponds to scattering and ionization to absorption. Progress in the field depends on developing multidimensional analytic methods, and obtaining experimental data for the physical processes of wall reflection, the neutral/plasma interaction, and for processes in fusion devices which are directly related to neutral transport, such as H/sub ..cap alpha../ emission rates, plenum pressures, and charge-exchange emission spectra.

  12. 42 CFR 493.927 - General immunology.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Anti-human immunodeficiency virus (HIV) Complement C3 Complement C4 Hepatitis markers (HBsAg, anti-HBc, HBeAg...Immunodeficiency virus Reactive or nonreactive. Complement C3 Target value ±3 SD. Complement C4...

  13. 42 CFR 493.927 - General immunology.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Anti-human immunodeficiency virus (HIV) Complement C3 Complement C4 Hepatitis markers (HBsAg, anti-HBc, HBeAg...Immunodeficiency virus Reactive or nonreactive. Complement C3 Target value ±3 SD. Complement C4...

  14. 42 CFR 493.927 - General immunology.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Anti-human immunodeficiency virus (HIV) Complement C3 Complement C4 Hepatitis markers (HBsAg, anti-HBc, HBeAg...Immunodeficiency virus Reactive or nonreactive. Complement C3 Target value ±3 SD. Complement C4...

  15. Human immunodeficiency virus type 1 membrane fusion mediated by a laboratory-adapted strain and a primary isolate analyzed by resonance energy transfer.

    PubMed Central

    Litwin, V; Nagashima, K A; Ryder, A M; Chang, C H; Carver, J M; Olson, W C; Alizon, M; Hasel, K W; Maddon, P J; Allaway, G P

    1996-01-01

    Previous studies of human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein-mediated membrane fusion have focused on laboratory-adapted T-lymphotropic strains of the virus. The goal of this study was to characterize membrane fusion mediated by a primary HIV-1 isolate in comparison with a laboratory-adapted strain. To this end, a new fusion assay was developed on the basis of the principle of resonance energy transfer, using HeLa cells stably transfected with gp120/gp41 from the T-lymphotropic isolate HIV-1LA1 or the macrophage-tropic primary isolate HIV-1JR-FL. These cells fused with CD4+ target cell lines with a tropism mirroring that of infection by the two viruses. Of particular note, HeLa cells expressing HIV-1JR-FL gp120/gp41 fused only with PM1 cells, a clonal derivative of HUT 78, and not with other T-cell or macrophage cell lines. These results demonstrate that the envelope glycoproteins of these strains play a major role in mediating viral tropism. Despite significant differences exhibited by HIV-1JR-FL and HIV-1LAI in terms of tropism and sensitivity to neutralization by CD4-based proteins, the present study found that membrane fusion mediated by the envelope glycoproteins of these viruses had remarkably similar properties. In particular, the degree and kinetics of membrane fusion were similar, fusion occurred at neutral pH and was dependent on the presence of divalent cations. Inhibition of HIV-1JR-FL envelope glycoprotein-mediated membrane fusion by soluble CD4 and CD4-IgG2 occurred at concentrations similar to those required to neutralize this virus. Interestingly, higher concentrations of these agents were required to inhibit HIV-1LAI envelope glycoprotein-mediated membrane fusion, in contrast to the greater sensitivity of HIV-1LAI virions to neutralization by soluble CD4 and CD4-IgG2. This finding suggests that the mechanisms of fusion inhibition and neutralization of HIV-1 are distinct. PMID:8709277

  16. Cryptococcal Meningoencephalitis in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome in Douala, Cameroon: A Cross Sectional Study

    PubMed Central

    Luma, Henry Namme; Temfack, Elvis; Halle, Marie Patrice; Tchaleu, Benjamin Clet Nguenkam; Mapoure, Yacouba Njankouo; Koulla-Shiro, Sinata

    2013-01-01

    Background: Cryptococcal meningoencephalitis (CM) kills about half a million human immunodeficiency virus (HIV) patients per year, mostly in Africa. Aim: The aim of this study was to determine the prevalence, clinical presentation and in-hospital outcome of CM among HIV-infected patients in Douala. Materials and Methods: A cross-sectional clinical note review of 672 HIV-1 patients’ files admitted from January 1 st 2004 to December 31 st 2009 at the Internal Medicine unit of the Douala General Hospital, Cameroon was performed. Only patients diagnosed of CM by microscopy of Indian ink stained cerebrospinal fluid (CSF) were studied. Results: The prevalence of CM in the study was 11.2%. Mean age of patients was 36.9 ? 12.7 years. Median cluster of differentiation 4 (CD4) cell count was 23 cells/?L, (interquartile range [IQR]: 10-61) and 62.7% of CD4 cell counts were >50 cells/?L. The most prevalent symptom was headache in 97.3% of patients. In CSF, median proteins was 0.9 g/L (IQR: 0.6-1); median glucose 0.2 g/L (IQR: 0.1-0.3) and median leucocyte count 54 cells/?L (IQR: 34-76) mostly of mixed cellularity. The case fatality rate was 52% and low CD4 cell count was strongly associated with death, odd ratio 4.6 (95% confidence interval: 2.6-8.0, P > 0.001). Conclusion: The high case fatality of CM in Douala warrants adequate diagnostic measures and optimization of standardized treatment to reduce mortality. PMID:24083225

  17. Analysis of variation of neutral point potential in neutral-point-clamped voltage source PWM inverters

    Microsoft Academic Search

    Satoshi Ogasawara; Hirofumi Akagi

    1993-01-01

    The authors present the analysis of the neutral-point potential variation of the neutral-point-clamped voltage source PWM (pulse-width-modulation) inverter (NPC-VSI) for AC motor drives and static VAr compensators (SVC). The potential variation is analyzed with the focus on the current flowing out of or into the neutral point of the DC link. The theoretical minimum capacity of the DC link capacitors

  18. T Cells Target APOBEC3 Proteins in Human Immunodeficiency Virus Type 1-Infected Humans and Simian Immunodeficiency Virus-Infected Indian Rhesus Macaques

    PubMed Central

    Champiat, Stéphane; Garrison, Keith E.; Raposo, Rui André Saraiva; Burwitz, Benjamin J.; Reed, Jason; Tandon, Ravi; York, Vanessa A.; Newman, Laura P.; Nimityongskul, Francesca A.; Wilson, Nancy A.; Almeida, Rafael R.; Martin, Jeffrey N.; Deeks, Steven G.; Rosenberg, Michael G.; Wiznia, Andrew A.; Spotts, Gerald E.; Pilcher, Christopher D.; Hecht, Fredrick M.; Ostrowski, Mario A.

    2013-01-01

    APOBEC3 proteins mediate potent antiretroviral activity by hypermutating the retroviral genome during reverse transcription. To counteract APOBEC3 and gain a replicative advantage, lentiviruses such as human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) have evolved the Vif protein, which targets APOBEC3 proteins for proteasomal degradation. However, the proteasome plays a critical role in the generation of T cell peptide epitopes. Whether Vif-mediated destruction of APOBEC3 proteins leads to the generation and presentation of APOBEC3-derived T cell epitopes on the surfaces of lentivirus-infected cells remains unknown. Here, using peptides derived from multiple Vif-sensitive APOBEC3 proteins, we identified APOBEC3-specific T cell responses in both HIV-1-infected patients and SIV-infected rhesus macaques. These results raise the possibility that these T cell responses may be part of the larger antiretroviral immune response. PMID:23536679

  19. Failure of low-dose recombinant human IL-2 to support the survival of virus-specific CTL clones infused into severe combined immunodeficient foals: lack of correlation between in vitro activity and in vivo efficacy

    PubMed Central

    Mealey, Robert H.; Littke, Matt H.; Leib, Steven R.; Davis, William C.; McGuire, Travis C.

    2010-01-01

    Although CTL are important for control of lentiviruses, including equine infectious anemia virus (EIAV), it is not known if CTL can limit lentiviral replication in the absence of CD4 help and neutralizing antibody. Adoptive transfer of EIAV-specific CTL clones into severe combined immunodeficient (SCID) foals could resolve this issue, but it is not known whether exogenous IL-2 administration is sufficient to support the engraftment and proliferation of CTL clones infused into immunodeficient horses. To address this question we adoptively transferred EIAV Rev-specific CTL clones into four EIAV-challenged SCID foals, concurrent with low-dose aldesleukin (180,000 U/m2), a modified recombinant human IL-2 (rhuIL-2) product. The dose was calculated based on the specific activity on equine PBMC in vitro, and resulted in plasma concentrations considered sufficient to saturate high affinity IL-2 receptors in humans. Despite specific activity on equine PBMC that was equivalent to recombinant equine IL-2 and another form of rhuIL-2, aldesleukin did not support the engraftment and expansion of infused CTL clones, and control of viral load and clinical disease did not occur. It was concluded that survival of Rev-specific CTL clones infused into EIAV-challenged SCID foals was not enhanced by aldesleukin at the doses used in this study, and that in vitro specific activity did not correlate with in vivo efficacy. Successful adoptive immunotherapy with CTL clones in immunodeficient horses will likely require higher doses of rhuIL-2, co-infusion of CD4+ T lymphocytes, or administration of equine IL-2. PMID:17727961

  20. Antibody-mediated protection against mucosal simian-human immunodeficiency virus challenge of macaques immunized with alphavirus replicon particles and boosted with trimeric envelope glycoprotein in MF59 adjuvant.

    PubMed

    Barnett, Susan W; Burke, Brian; Sun, Yide; Kan, Elaine; Legg, Harold; Lian, Ying; Bost, Kristen; Zhou, Fengmin; Goodsell, Amanda; Zur Megede, Jan; Polo, John; Donnelly, John; Ulmer, Jeffrey; Otten, Gillis R; Miller, Christopher J; Vajdy, Michael; Srivastava, Indresh K

    2010-06-01

    We have previously shown that rhesus macaques were partially protected against high-dose intravenous challenge with simian-human immunodeficiency virus SHIV(SF162P4) following sequential immunization with alphavirus replicon particles (VRP) of a chimeric recombinant VEE/SIN alphavirus (derived from Venezuelan equine encephalitis virus [VEE] and the Sindbis virus [SIN]) encoding human immunodeficiency virus type 1 HIV-1(SF162) gp140DeltaV2 envelope (Env) and trimeric Env protein in MF59 adjuvant (R. Xu, I. K. Srivastava, C. E. Greer, I. Zarkikh, Z. Kraft, L. Kuller, J. M. Polo, S. W. Barnett, and L. Stamatatos, AIDS Res. Hum. Retroviruses 22:1022-1030, 2006). The protection did not require T-cell immune responses directed toward simian immunodeficiency virus (SIV) Gag. We extend those findings here to demonstrate antibody-mediated protection against mucosal challenge in macaques using prime-boost regimens incorporating both intramuscular and mucosal routes of delivery. The macaques in the vaccination groups were primed with VRP and then boosted with Env protein in MF59 adjuvant, or they were given VRP intramuscular immunizations alone and then challenged with SHIV(SF162P4) (intrarectal challenge). The results demonstrated that these vaccines were able to effectively protect the macaques to different degrees against subsequent mucosal SHIV challenge, but most noteworthy, all macaques that received the intramuscular VRP prime plus Env protein boost were completely protected. A statistically significant association was observed between the titer of virus neutralizing and binding antibodies as well as the avidity of anti-Env antibodies measured prechallenge and protection from infection. These results highlight the merit of the alphavirus replicon vector prime plus Env protein boost vaccine approach for the induction of protective antibody responses and are of particular relevance to advancing our understanding of the potential correlates of immune protection against HIV infection at a relevant mucosal portal of entry. PMID:20392857

  1. Zeta Chain of the T-Cell Receptor Interacts with nef of Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 2

    Microsoft Academic Search

    ANITA Y. M. HOWE; JAE U. JUNG; RONALD C. DESROSIERS

    1998-01-01

    A truncated version of the nef gene of simian immunodeficiency virus SIVmac239 capable of encoding amino acids 98 to 263 was used as bait to screen a cDNA library from activated lymphocytes in a yeast two-hybrid system. The zeta chain of the T-cell receptor (TCRz) was found to interact specifically not only with truncated SIV nef in yeast cells but

  2. Operations about Hip in Human Immunodeficiency Virus-Positive Patients

    PubMed Central

    Yoo, Jeong Joon; Chun, Sae Hyung; Kwon, Young Sam; Koo, Kyung-Hoi; Yoon, Kang Sup

    2010-01-01

    Background The number of human immunodeficiency virus (HIV)-infected patients is increasing constantly, and it is well known that there is a significantly high prevalence of osteonecrosis of the femoral head in HIV-infected patients. Therefore, it is important to develop methods that can ensure the safety of both the patients and medical personnel who participate in surgery on HIV-infected patients. Recently, the authors performed 8 procedures on 5 HIV-infected patients. This paper reports our experience. Methods This study examined the medical records and radiological studies of 5 HIV-infected patients who had undergone surgery around the hip joint from January, 2005 to September, 2007. During the procedures, their mean age was 38.6 years (range, 23 to 53 years) and all were male. Four of them were under an anti-retroviral therapy program. The reasons for the operations were nonunion of the femoral shaft after trauma in two patients and osteonecrosis of both femoral heads in three. One autologous bone grafting, one screw fixation with autologous bone grafting, five total hip replacement arthroplasties, and one multiple drilling were performed. All procedures were carried out according to the guidelines of HIV infection control made by the Korea Centers for Disease Control and Prevention. The mean follow-up period was 16.6 months (range, 4 to 37 months). Results The preoperative CD4 count was 130 in one patient, and 200 to 499 in the other 4. The viral loads were 15100 and 420 in two patients, and negative in the other 3. Bony union was achieved in those who had undergone autologous bone grafting. There were significant improvements in both the Harris Hip Score and functional state in those who had total hip replacement arthroplasty. There were no immediate postoperative complications, such as infection. During the follow-up period, one patient died from esophageal variceal bleeding. However, no surgery-related complications were observed in the other 4 patients. Conclusions There were no significant complications in HIV-infected patients after the operations around the hip joint when their preoperative immunity was optimal. In addition, the safety of medical personnel can be assured when the operation is performed in line with the guidelines of HIV infection control. PMID:20190997

  3. Optimization of Human Immunodeficiency Virus Treatment During Incarceration

    PubMed Central

    Meyer, Jaimie P.; Cepeda, Javier; Wu, Johnny; Trestman, Robert L.; Altice, Frederick L.; Springer, Sandra A.

    2014-01-01

    IMPORTANCE Human immunodeficiency virus (HIV) management in correctional settings is logistically feasible, but HIV-related outcomes before release have not been recently systematically examined. OBJECTIVE To evaluate HIV treatment outcomes throughout incarceration, including jail and prison. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of longitudinally linked demographic, pharmacy, and laboratory data on 882 prisoners within the Connecticut Department of Correction (2005–2012) with confirmed HIV infection, who were continually incarcerated 90 days or more, had at least 2 HIV-1 RNA and CD4 lymphocyte measurements, and were prescribed antiretroviral therapy. MAIN OUTCOMES AND MEASURES Three electronic databases (correctional, laboratory, and pharmacy) were integrated to assess HIV viral suppression (HIV-1 RNA levels, <400 copies/mL) on intake and release. Secondary outcomes were mean change in log-transformed HIV-1 RNA levels and mean change in CD4 lymphocyte count during incarceration. Demographic characteristics, prescribed pharmacotherapies, receipt of directly observed therapy, and duration of incarceration were analyzed as possible explanatory variables for HIV viral suppression in logistic regression models. RESULTS Among 882 HIV-infected prisoners with 1185 incarceration periods, mean HIV-1 RNA level decreased by 1.1 log10 and CD4 lymphocyte count increased by 98 cells/?L over time, with a higher proportion achieving viral suppression by release compared with entry (70.0% vs 29.8%; P < .001); 36.9% of antiretroviral therapy (ART) regimens were changed during incarceration. After adjusting for baseline HIV-1 RNA level, prerelease viral suppression correlated with female sex (adjusted odds ratio, 1.81; 95% CI, 1.26–2.59) and psychiatric disorder severity below the sample median (adjusted odds ratio, 1.50; 95% CI, 1.12–1.99), but not race/ethnicity, incarceration duration, ART regimen or dosing strategy, or directly observed therapy. CONCLUSIONS AND RELEVANCE Though just one-third of HIV-infected prisoners receiving ART entered correctional facilities with viral suppression, HIV treatment was optimized during incarceration, resulting in the majority achieving viral suppression by release. Treatment for HIV within prison is facilitated by a highly structured environment and, when combined with simple well-tolerated ART regimens, can result in viral suppression during incarceration. In the absence of important and effective community-based resources, incarceration can be an opportunity of last resort to initiate continuous ART for individual health and, following the “treatment as prevention” paradigm, potentially reduce the likelihood of HIV transmission to others after release if continuity of HIV care is sustained. PMID:24687044

  4. Intravenous immunoglobulin induces proliferation and immunoglobulin synthesis from B cells of patients with common variable immunodeficiency: a mechanism underlying the beneficial effect of IVIg in primary immunodeficiencies.

    PubMed

    Bayry, Jagadeesh; Fournier, Emilie M; Maddur, Mohan S; Vani, Janakiraman; Wootla, Bharath; Sibéril, Sophie; Dimitrov, Jordan D; Lacroix-Desmazes, Sébastien; Berdah, Mikael; Crabol, Yoann; Oksenhendler, Eric; Lévy, Yves; Mouthon, Luc; Sautès-Fridman, Catherine; Hermine, Olivier; Kaveri, Srini V

    2011-02-01

    Common variable immunodeficiency (CVID) is associated with low serum immunoglobulin concentrations and an increased susceptibility to infections and autoimmune diseases. The treatment of choice for CVID patients is replacement intravenous immunoglobulin (IVIg) therapy. IVIg has been beneficial in preventing or alleviating the severity of infections and autoimmune and inflammatory process in majority of CVID patients. Although the mechanisms of action of IVIg given as 'therapeutic high dose' in patients with autoimmune diseases are well studied, the underlying mechanisms of beneficial effects of IVIg in primary immunodeficiencies are not completely understood. Therefore we investigated the effect of 'replacement dose' of IVIg by probing its action on B cells from CVID patients. We demonstrate that IVIg at low doses induces proliferation and immunoglobulin synthesis from B cells of CVID patients. Interestingly, B cell stimulation by IVIg is not associated with induction of B cell effector cytokine IFN-? and of transcription factor T-bet. Together, our results indicate that in some CVID patients, IVIg rectifies the defective signaling of B cells normally provided by T cells and delivers T-independent signaling for B cells to proliferate. IVIg 'replacement therapy' in primary immunodeficiencies is therefore not a merepassive transfer of antibodies to prevent exclusively the recurrent infections; rather it has an active role in regulating autoimmune and inflammatory responses through modulating B cell functions and thus imposing dynamic equilibrium of the immune system. PMID:20970960

  5. Reconciling empirical ecology with neutral community models.

    PubMed

    Holyoak, Marcel; Loreau, Michel

    2006-06-01

    Neutral community models embody the idea that individuals are ecologically equivalent, having equal fitness over all environmental conditions, and describe how the spatial dynamics and speciation of such individuals can produce a wide range of patterns of distribution, diversity, and abundance. Neutral models have been controversial, provoking a rush of tests and comments. The debate has been spurred by the suggestion that we should test mechanisms. However, the mechanisms and the spatial scales of interest have never clearly been described, and consequently, the tests have often been only peripherally relevant. At least two mechanisms are present in spatially structured neutral models. Dispersal limitation causes clumping of a species, which increases the strength of intraspecific competition and reduces the strength of interspecific competition. This may prolong coexistence and enhance local and regional diversity. Speciation is present in some neutral models and gives a donor-controlled input of new species, many of which remain rare or are short lived, but which directly add to species diversity. Spatial scale is an important consideration in neutral models. Ecological equivalence and equal fitness have implicit spatial scales because dispersal limitation and its emergent effects operate at population levels, and populations and communities are defined at a chosen spatial scale in recent neutral models; equality is measured relative to a metacommunity, and this necessitates defining the spatial scale of that metacommunity. Furthermore, dispersal has its own scales. Thorough empirical tests of neutral models will require both tests of mechanisms and pattern-producing ability, and will involve coupling theoretical models and experiments. PMID:16869411

  6. Characterization of a Large Panel of Rabbit Monoclonal Antibodies against HIV-1 gp120 and Isolation of Novel Neutralizing Antibodies against the V3 Loop.

    PubMed

    Qin, Yali; Banerjee, Saikat; Agrawal, Aditi; Shi, Heliang; Banasik, Marisa; Lin, Feng; Rohl, Kari; LaBranche, Celia; Montefiori, David C; Cho, Michael W

    2015-01-01

    We recently reported the induction of potent, cross-clade neutralizing antibodies (nAbs) against Human Immunodeficiency Virus type-1 (HIV-1) in rabbits using gp120 based on an M-group consensus sequence. To better characterize these antibodies, 93 hybridomas were generated, which represent the largest panel of monoclonal antibodies (mAbs) ever generated from a vaccinated rabbit. The single most frequently recognized epitope of the isolated mAbs was at the very C-terminal end of the protein (APTKAKRRVVEREKR), followed by the V3 loop. A total of seven anti-V3 loop mAbs were isolated, two of which (10A3 and 10A37) exhibited neutralizing activity. In contrast to 10A3 and most other anti-V3 loop nAbs, 10A37 was atypical with its epitope positioned more towards the C-terminal half of the loop. To our knowledge, 10A37 is the most potent and broadly neutralizing anti-V3 loop mAb induced by vaccination. Interestingly, all seven anti-V3 loop mAbs competed with PGT121, suggesting a possibility that early induction of potent anti-V3 loop antibodies could prevent induction of more broadly neutralizing PGT121-like antibodies that target the conserved base of the V3 loop stem. PMID:26039641

  7. Characterization of a Large Panel of Rabbit Monoclonal Antibodies against HIV-1 gp120 and Isolation of Novel Neutralizing Antibodies against the V3 Loop

    PubMed Central

    Qin, Yali; Shi, Heliang; Banasik, Marisa; Lin, Feng; Rohl, Kari; LaBranche, Celia; Montefiori, David C.; Cho, Michael W.

    2015-01-01

    We recently reported the induction of potent, cross-clade neutralizing antibodies (nAbs) against Human Immunodeficiency Virus type-1 (HIV-1) in rabbits using gp120 based on an M-group consensus sequence. To better characterize these antibodies, 93 hybridomas were generated, which represent the largest panel of monoclonal antibodies (mAbs) ever generated from a vaccinated rabbit. The single most frequently recognized epitope of the isolated mAbs was at the very C-terminal end of the protein (APTKAKRRVVEREKR), followed by the V3 loop. A total of seven anti-V3 loop mAbs were isolated, two of which (10A3 and 10A37) exhibited neutralizing activity. In contrast to 10A3 and most other anti-V3 loop nAbs, 10A37 was atypical with its epitope positioned more towards the C-terminal half of the loop. To our knowledge, 10A37 is the most potent and broadly neutralizing anti-V3 loop mAb induced by vaccination. Interestingly, all seven anti-V3 loop mAbs competed with PGT121, suggesting a possibility that early induction of potent anti-V3 loop antibodies could prevent induction of more broadly neutralizing PGT121-like antibodies that target the conserved base of the V3 loop stem. PMID:26039641

  8. Neutrality and the Evolvability of Boolean Function Landscape

    Microsoft Academic Search

    Tina Yu; Julian F. Miller

    2001-01-01

    This work is a study of neutrality in the context of Evolutionary Computation systems. In particular, we introduce the use of explicit neutral- ity with an integer string coding scheme to allow neutrality to be measured during evolution. We tested this method on a Boolean benchmark problem. The experimental results indicate that there is a positive relationship between neutrality and

  9. Antibodies with High Avidity to the gp120 Envelope Protein in Protection from Simian Immunodeficiency Virus SIVmac251 Acquisition in an Immunization Regimen That Mimics the RV-144 Thai Trial

    PubMed Central

    Pegu, Poonam; Vaccari, Monica; Gordon, Shari; Keele, Brandon F.; Doster, Melvin; Guan, Yongjun; Ferrari, Guido; Pal, Ranajit; Ferrari, Maria Grazia; Whitney, Stephen; Hudacik, Lauren; Billings, Erik; Rao, Mangala; Montefiori, David; Tomaras, Georgia; Alam, S. Munir; Fenizia, Claudio; Lifson, Jeffrey D.; Stablein, Donald; Tartaglia, Jim; Michael, Nelson; Kim, Jerome; Venzon, David

    2013-01-01

    The recombinant canarypox vector, ALVAC-HIV, together with human immunodeficiency virus (HIV) gp120 envelope glycoprotein, has protected 31.2% of Thai individuals from HIV acquisition in the RV144 HIV vaccine trial. This outcome was unexpected, given the limited ability of the vaccine components to induce CD8+ T-cell responses or broadly neutralizing antibodies. We vaccinated macaques with an immunization regimen intended to mimic the RV144 trial and exposed them intrarectally to a dose of the simian immunodeficiency virus SIVmac251 that transmits few virus variants, similar to HIV transmission to humans. Vaccination induced anti-envelope antibodies in all vaccinees and CD4+ and CD8+ T-cell responses. Three of the 11 macaques vaccinated with ALVAC-SIV/gp120 were protected from SIVmac251 acquisition, but the result was not significant. The remaining vaccinees were infected and progressed to disease. The magnitudes of vaccine-induced SIVmac251-specific T-cell responses and binding antibodies were not significantly different between protected and infected animals. However, sera from protected animals had higher avidity antibodies to gp120, recognized the variable envelope regions V1/V2, and reduced SIVmac251 infectivity in cells that express high levels of ?4?7 integrins, suggesting a functional role of antibodies to V2. The current results emphasize the utility of determining the titer of repeated mucosal challenge in the preclinical evaluation of HIV vaccines. PMID:23175374

  10. LFA-1 IMMUNODEFICIENCY DISEASE Definition of the Genetic Defect and Chromosomal Mapping of a and a

    E-print Network

    Springer, Timothy A.

    LFA-1 IMMUNODEFICIENCY DISEASE Definition of the Genetic Defect and Chromosomal Mapping of a and a Subunits of the Lymphocyte Function-associated Antigen 1 (LFA-1) by Complementation in Hybrid Cells adhesion proteins, LFA-1 (lymphocyte function-associated antigen 1),' Mac-1 (macrophage antigen 1), and p

  11. Treatment of diarrhoea in human immunodeficiency virus-infected patients with immunoglobulins from bovine colostrum

    Microsoft Academic Search

    J. A. Rump; R. Arndt; A. Arnold; C. Bendick; H. Dichtelmüller; M. Franke; E. B. Helm; H. Jäger; B. Kampmann; P. Kolb; W. Kreuz; R. Lissner; W. Meigel; P. Ostendorf; H. H. Peter; A. Plettenberg; I. Schedel; H. W. Stellbrink; W. Stephan

    1992-01-01

    Diarrhoea and weight loss are found in more than 50% of patients with the acquired immunodeficiency syndrome (AIDS). In some patients the symptoms can be very severe, leading to death even in the absence of opportunistic infections. In 30% of these patients, enteric pathogens cannot be identified, and approximately only half of the identifiable aetiologic agents of diarrhoea in patients

  12. Liver Enlargement Associated with Opportunistic Infections in Patients with Human Immunodeficiency Virus Infection

    Microsoft Academic Search

    Dragica Terzic; Branko Brmbolic; Djordje Jevtovic; Brankica Dupanovic; Milos Kora; Dubravka Selemovic; Neda Svirtlih; Nenad Draskovic; Boban Mugosa; Ivan Boricic; Zoran Terzic

    Background & Aim. Liver disease is commonly present in human immunodeficiency virus (HIV) infection. The aim was to determine the frequency of liver enlargement and its association with opportunistic infections in patients with HIV infection. Patients and methods. A total of 400 HIV-infected patients were investigated. Commercial kits (Ortho EIA; BioRad, ELISA) were used for detection of serum specific antibodies

  13. Immunodeficiency virus exploitation of dendritic cells in the early steps of infection

    Microsoft Academic Search

    Natalia Teleshova; Ines Frank; Melissa Pope

    2003-01-01

    The unique capacity of dendritic cells (DCs) to capture and process pathogens for pre- sentation to the immune system, combined with their capacity to express costimulatory and adhe- sion molecules as well as cytokines and chemo- kines, renders them powerful antigen-presenting cells. However, immunodeficiency viruses hijack DCs to facilitate virus dissemination while subvert- ing effective immune activation. Depending on the

  14. C correlation spectroscopy of membrane-associated and uniformly labeled human immunodeficiency virus and influenza

    E-print Network

    Weliky, David

    immunodeficiency virus and influenza fusion peptides: Amino acid-type assignments and evidence for multiple and influenza are "enveloped" by a membrane and infection of a host cell begins with joining or "fusion and for the influenza virus, these fusion proteins contain an 20-residue apolar "fusion peptide" that binds to target

  15. Role of Human Immunodeficiency Virus in Primary Pulmonary HypertensionCase Reports

    Microsoft Academic Search

    Adriano M. Pellicelli; Fabrizio Palmieri; Cecilia DAmbrosio; Alessia Rianda; Evangelo Boumis; Enrico Girardi; Giorgio Antonucci; Carmelo DAmato; Maria Clotilde Borgia

    1998-01-01

    Previous cases of pulmonary hypertension (PH) in human immunodeficiency virus (HIV) infection have been reported in the literature. The role of HIV in PH is still debatable. The purpose of this report was to analyze whether HIV plays a direct or indirect role in PH pathogenesis. Between February and November 1997, 56 HIV-infected patients with cardiac symptoms and signs were

  16. Human Immunodeficiency Virus and Hepatitis C Virus Coinfection: Epidemiology, Natural History, Therapeutic Options and Clinical Management

    Microsoft Academic Search

    G. Verucchi; L. Calza; R. Manfredi; F. Chiodo

    2004-01-01

    Due to shared risk factors for transmission, coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is a very common event. The prevalence of HCV infection among HIV-positive patients averages about 35% in the United States and Europe, but in clinical populations where there is a great prevalence of intravenous drug use as a risk factor for acquiring

  17. Hypothesis of snake and insect venoms against Human Immunodeficiency Virus: a review

    Microsoft Academic Search

    Ramachandran Meenakshisundaram; Shah Sweni; Ponniah Thirumalaikolundusubramanian

    2009-01-01

    BACKGROUND: Snake and insect venoms have been demonstrated to have beneficial effects in the treatment of certain diseases including drug resistant human immunodeficiency virus (HIV) infection. We evaluated and hypothesized the probable mechanisms of venoms against HIV. METHODS: Previous literatures published over a period of 30 years (1979-2009) were searched using the key words snake venom, insect venom, mechanisms and

  18. Treatment of Depressive Symptoms in Human Immunodeficiency Virus-Positive Patients

    Microsoft Academic Search

    John C. Markowitz; James H. Kocsis; Baruch Fishman; Lisa A. Spielman; Lawrence B. Jacobsberg; Allen J. Frances; Gerald L. Klerman; Samuel W. Perry

    1998-01-01

    Background: This randomized clinical trial com- pared 16-week interventions with interpersonal psy- chotherapy, cognitive behavioral therapy, supportive psychotherapy, and supportive psychotherapy with imipramine for human immunodeficiency virus (HIV)-positive patients with depressive symptoms. Methods: Subjects (N = 101; 85 male, 16 female) with known HIV seropositivity for at least 6 months were ran- domized to 16 weeks of treatment. Inclusion criteria

  19. A Call to Include Severe Combined Immunodeficiency in Newborn Screening Program

    PubMed Central

    Somech, Raz; Etzioni, Amos

    2014-01-01

    Quantification of the T cell receptor excision circles (TRECs) has recently emerged as a useful non-invasive clinical and research tool to investigate thymic activity. It allows the identification of T cell production by the thymus. Quantification of TREC copies has recently been implemented as the preferred test to screen neonates with severe combined immunodeficiency (SCID) or significant lymphopenia. Neonatal genetic screening for SCID is highly important in countries with high rates of consanguinous marriages, such as Israel, and can be used for early diagnosis, enabling prompt therapeutic intervention that will save lives and improve the outcome of these patients. TREC measurement is also applicable in clinical settings where T cell immunity is involved, including any T cell immunodeficiencies, HIV infection, the aging process, autoimmune diseases, and immune reconstitution after bone marrow transplantation. TAKE-HOME MESSAGES Severe combined immunodeficiency, a life-threatening condition, can be detected by neonatal screening. The earlier the detection and the quicker the implementation of appropriate treatment, the greater the likelihood for improved outcome, even cure, for the affected children. TRECs and KRECs quantification are useful screening tests for severe T and B cell immunodeficiency and can be used also to evaluate every medical condition involving T and B cell immunity. PMID:24498508

  20. Regulation of Macrophage Activation and Human Immunodeficiency Virus Production by InvasiveSalmonellaStrains

    Microsoft Academic Search

    STEVEN B. MIZEL; LOUIS S. KUCERA; STEPHEN H. RICHARDSON; FEDERICA CIACCI; ANDNATHAN P. IYER

    Salmonellae possess the ability to adhere to and invade macrophages and in so doing trigger a number of intracellular events that are associated with cellular activation. As an initial approach to defining the mech- anisms by which invasive salmonellae alter macrophage function, we have explored the impact of Salmonella infection on the production of human immunodeficiency virus (HIV) in U1

  1. Incorporation of High Levels of Chimeric Human Immunodeficiency Virus Envelope Glycoproteins into Virus-Like Particles

    Microsoft Academic Search

    Bao-Zhong Wang; Weimin Liu; Sang-Moo Kang; Munir Alam; Chunzi Huang; Ling Ye; Yuliang Sun; Yingying Li; Denise L. Kothe; Peter Pushko; Terje Dokland; Barton F. Haynes; Gale Smith; Beatrice H. Hahn; Richard W. Compans

    2007-01-01

    The human immunodeficiency virus (HIV) envelope (Env) protein is incorporated into HIV virions or virus-like particles (VLPs) at very low levels compared to the glycoproteins of most other enveloped viruses. To test factors that influence HIV Env particle incorporation, we generated a series of chimeric gene constructs in which the coding sequences for the signal peptide (SP), transmembrane (TM), and

  2. Lack of evidence for transmission of human immunodeficiency virus through vaginal intercourse

    Microsoft Academic Search

    Stuart Brody

    1995-01-01

    Research in determining risks for human immunodeficiency virus (HIV) transmission is confounded by many issues. They include lack of clarity or specificity in terminology used, respondents misunderstanding of questions, and lying. The base rate of lying (or social desirability responding) by itself is sufficient to account for the small percentage of Americans and Europeans claiming “heterosexual” transmission from partners not

  3. Engineered Vaginal Lactobacillus Strain for Mucosal Delivery of the Human Immunodeficiency Virus Inhibitor Cyanovirin-N

    Microsoft Academic Search

    Xiaowen Liu; Laurel A. Lagenaur; David A. Simpson; Kirsten P. Essenmacher; Courtney L. Frazier-Parker; Yang Liu; Daniel Tsai; Srinivas S. Rao; Dean H. Hamer; Thomas P. Parks; Peter P. Lee; Qiang Xu

    2006-01-01

    Women are at significant risk of human immunodeficiency virus (HIV) infection, with the cervicovaginal mucosa serving as a major portal for virus entry. Female-initiated preventatives, including topical microbi- cides, are urgently needed to help curtail the HIV\\/AIDS pandemic. Here we report on the development of a novel, live microbicide that employs a natural vaginal strain of Lactobacillus jensenii engineered to

  4. Influence of C4 null genes on infection with human immunodeficiency virus

    Microsoft Academic Search

    P U Cameron; T J Cobain; W J Zhang; P H Kay; R L Dawkins

    1988-01-01

    The hypothesis that complement is important in the host response to human immunodeficiency virus (HIV) was tested. Complement C4 and Bf allotypes were determined in 26 patients who fulfilled the diagnostic criteria for persistent generalised lymphadenopathy due to HIV, 72 homosexuals who were negative for antibody to HIV, and 185 control subjects drawn from the local population. HLA-A, B, and

  5. Human Immunodeficiency Virus-Like Particles Produced by a Vaccinia Virus Expression Vector

    Microsoft Academic Search

    Velissarios Karacostas; Kunio Nagashima; Matthew A. Gonda; Bernard Moss

    1989-01-01

    Infectious retrovirus particles consist of a core structure containing RNA and gag-pol polypeptides surrounded by a lipid membrane studded with env proteins. A recombinant vaccinia virus was designed to express the entire gag-pol precursor protein of the human immunodeficiency virus type 1. Synthesis and processing of gag proteins occurred in mammalian cells infected with this live recombinant virus, and reverse

  6. Encephalitis, lymphoid tissue depletion and secondary diseases associated with bovine immunodeficiency virus in a dairy herd

    Microsoft Academic Search

    T. G. Snider; D. G. Luther; B. F. Jenny; P. G. Hoyt; J. K. Battles; W. H. Ennis; J. Balady; U. Blas-Machado; T. X. Lemarchand; M. A. Gonda

    1996-01-01

    Encephalitis, lymphoid tissue depletion and secondary infections occurred over a 5-yr-period in Holstein cows infected with bovine immunodeficiency virus (BIV). There were 59 cattle studied, the majority during 1991, when a severe environmental stress occurred, each with one or more primary causes of death, natural or by euthanasia, and most with several secondary diseases. The encephalitis was characterized by meningeal,

  7. Basal Cortisol Levels and Correlates of Hypoadrenalism in Patients with Human Immunodeficiency Virus Infection

    Microsoft Academic Search

    Chukwuma O. Ekpebegh; Anthonia O. Ogbera; Benjamin Longo-Mbenza; Ernesto Blanco-Blanco; Ajani Awotedu; Patrick Oluboyo

    2011-01-01

    Objective: To determine the frequency of occurrence of hypoadrenalism in patients with human immunodeficiency virus (HIV) infection and document the clinical correlates of hypoadrenalism for this group of patients. Subjects and Methods: A descriptive study was carried out on 66 hospitalized HIV patients in a semi-urban setting of South Africa. Hypoadrenalism was diagnosed based on a basal cortisol level of

  8. Human immunodeficiency virus, hepatitis B, C and D in Bangladesh's trucking industry: prevalence and risk factors

    Microsoft Academic Search

    Laura Gibney; Parwez Choudhury

    2001-01-01

    Background Human immunodeficiency virus (HIV) and hepatitis B and C, viral infections with shared percutaneous, mucosal and perinatal routes of transmission, are responsible for serious morbidity and mortality globally. In Bangladesh there is a dearth of research on prevalence and risk factors for these diseases. This study examines the prevalence of HIV and hepatitis (B, C, D) and risk factors

  9. Brain pathology induced by infection with the human immunodeficiency virus (HIV)

    Microsoft Academic Search

    H. Budka; G. Costanzi; S. Cristina; A. Lechi; C. Parravicini; R. Trabattoni; L. Vago

    1987-01-01

    Neuropathological examination of brain tissue of 100 patients with infection by the human immunodeficiency virus (HIV), including 98 with clinically manifest acquired immune deficiency syndrome (AIDS), revealed distinct multifocal-disseminated and diffuse brain tissue lesions, which can be regarded as HIV-induced brain lessions: multifocal giant cell encephalitis (MGCE; 4) and progressive diffuse leukoencephalopathy (PDL; 25). These lesions were found in 38

  10. Monitoring Resistance to Human Immunodeficiency Virus Type 1 Protease Inhibitors by Pyrosequencing

    Microsoft Academic Search

    KARIN WILBE; THOMAS LEITNER; BO HEJDEMAN; JAN ALBERT

    2001-01-01

    The emergence of drug-resistant viral variants is the inevitable consequence of incomplete suppression of human immunodeficiency virus type 1 (HIV-1) replication during treatment with antiretroviral drugs. Se- quencing to determine the resistance profiles of these variants has become increasingly important in the clinical management of HIV-1 patients, both in the initial design of a therapeutic plan and in selecting a

  11. Comprehensive Bioinformatic Analysis of the Specificity of Human Immunodeficiency Virus Type 1 Protease

    Microsoft Academic Search

    Liwen You; Daniel Garwicz; Thorsteinn Rognvaldsson

    2005-01-01

    Rapidly developing viral resistance to licensed human immunodeficiency virus type 1 (HIV-1) protease inhibitors is an increasing problem in the treatment of HIV-infected individuals and AIDS patients. A rational design of more effective protease inhibitors and discovery of potential biological substrates for the HIV-1 protease require accurate models for protease cleavage specificity. In this study, several popular bioinformatic machine learning

  12. High Rate of Recombination throughout the Human Immunodeficiency Virus Type 1 Genome

    Microsoft Academic Search

    AMANDA E. JETZT; HONG YU; GEORGE J. KLARMANN; YACOV RON; BRADLEY D. PRESTON; JOSEPH P. DOUGHERTY

    2000-01-01

    The diploid nature of human immunodeficiency virus type 1 (HIV-1) indicates that recombination serves a central function in virus replication and evolution. Previously, while examining the nature of obligatory primer strand transfers during reverse transcription, a high rate of recombination was observed at the ends of the viral genome within the viral long terminal repeats, prompting the following question: does

  13. Validity of the Quality of Well-Being Scale for Persons With Human Immunodeficiency Virus Infection

    Microsoft Academic Search

    ROBERT M. KAPLAN; JOHN P. ANDERSON; THOMAS L. PATTERSON; J. ALLEN MCCUTCHAN; JAMES D. WEINRICH; ROBERT K. HEATON

    1 To evaluate the validity of the Quality of Well-Being Scale (QWB) for studies of patients with human immunodeficiency virus (HIV) disease, 514 men were studied who were divided among four categories: Centers for Disease Control and Prevention (CDC) Group A (N = 272), CDC-B (N = 81), CDC-C (N = 47), and uninfected male controls (N = 114). The

  14. The changing spectrum of rheumatic disease in human immunodeficiency virus infection

    Microsoft Academic Search

    John D. Reveille

    2000-01-01

    Context: Although it has been known for over 15 years that a number of rheumatic diseases occur in patients with human immunodeficiency virus (HIV) infection, increasing knowledge about these disorders and advances in HIV treatment need to be considered in approaching patients with HIV-associated rheumatic disease. Objective: To examine the clinical, pathologic, and therapeutic features of HIV-associated rheumatic diseases in

  15. Evolution of structural proteins of feline immunodeficiency virus: molecular epidemiology and evidence of selection for change

    Microsoft Academic Search

    M. A. Rigby; E. C. Holmes; M. Pistello; A. Mackay; A. J. Leigh Brown; J. C. Neil

    1993-01-01

    The DNA sequences of structural genes of several U.K. and European isolates of feline immunodeficiency virus (FIV) were determined and compared with those of other worldwide isolates. Phylogenetic analyses of both gag and env sequences demonstrate that a Japanese isolate represents a distinct sequence subgroup, with corrected amino acid distances to the other isolates averaging 23 % in env and

  16. Dose response effects of feline immunodeficiency virus PPR strain infection in cats 

    E-print Network

    Hokanson, Regina Marie

    1998-01-01

    Feline immunodeficiency virus (F1V) causes an immune phics. deficiency disease in cats similar to HIV-AIDS in humans. FIV-specific antibodies have been found in symptomatic and asymptomatic, domestic and non-domestic, cats world-wide. Little...

  17. Basic Residues in Human Immunodeficiency Virus Type 1 Nucleocapsid Promote Virion Assembly via Interaction with RNA

    Microsoft Academic Search

    ANDREA CIMARELLI; SARA SANDIN; STEFAN HOGLUND; JEREMY LUBAN

    2000-01-01

    Retroviral Gag polyproteins drive virion assembly by polymerizing to form a spherical shell that lines the inner membrane of nascent virions. Deletion of the nucleocapsid (NC) domain of the Gag polyprotein disrupts assembly, presumably because NC is required for polymerization. Human immunodeficiency virus type 1 NC possesses two zinc finger motifs that are required for specific recognition and packaging of

  18. The Connections between Childhood Sexual Abuse and Human Immunodeficiency Virus Infection: Implications for Interventions

    ERIC Educational Resources Information Center

    Tarakeshwar, Nalini; Fox, Ashley; Ferro, Carol; Khawaja, Shazia; Kochman, Arlene; Sikkema, Kathleen J.

    2005-01-01

    A qualitative study was conducted with 28 women who are human immunodeficiency virus (HIV)-positive and have experienced childhood sexual abuse (CSA) in order to examine (1) the challenges generated by the experience of sexual abuse and related coping strategies, (2) the impact of the HIV diagnosis on their coping strategies, and (3) the links…

  19. Therapeutic Cannabis (Marijuana) as an Antiemetic and Appetite Stimulant in Persons with Acquired Immunodeficiency Syndrome (AIDS)

    Microsoft Academic Search

    Richard E. Bayer

    2001-01-01

    Acquired immunodeficiency syndrome (AIDS) is a common cause of death among young adults in the USA. AIDS wasting syndrome is the most common clinical presentation of AIDS. Antiretroviral drug therapy has improved the prognosis of persons with AIDS, but also contributed side effects, particularly nausea and anorexia. Case reports demonstrate persons with AIDS use cannabis as medicine tocontrol nausea, anorexia,

  20. Candida Esophagitis in a Human Immunodeficiency Virus-1-Positive Elite Controller With Hepatitis C Virus Cirrhosis

    PubMed Central

    Chen, Anders; Shieh, Eugenie; Brinkley, Sherilyn; Blankson, Joel N.

    2014-01-01

    We describe a case of Candida esophagitis in a human immunodeficiency virus elite controller with a preserved CD4 count, a population in which opportunistic infections are almost never seen. The patient has hepatitis C virus coinfection and compensated cirrhosis, suggesting a possible multifactorial etiology of immune dysregulation. PMID:25734179

  1. Multilocular thymic cysts in children with human immunodeficiency virus infection: Clinical and pathologic aspects

    Microsoft Academic Search

    H. Udo Kontny; John W. Sleasman; Douglas W. Kingma; Elaine S. Jaffe; Nilo A. Avila; Philip A. Pizzo; Brigitta U. Mueller

    1997-01-01

    Background: Children with human immunodeficiency virus (HIV) infection have an increased susceptibility to severe and unusual infections, malignancies, and disorders characterized by abnormal lymphoproliferation (e.g., lymphoid interstitial pneumonitis). We report a novel disease entity associated with pediatric HIV infection that is characterized by massive enlargement of the thymus as a result of lymphoid hyperplasia and multicystic changes.Methods: Eight patients with

  2. Molecular defects in T- and B-cell primary immunodeficiency diseases

    Microsoft Academic Search

    Prashant P. Ponda; Charlotte Cunningham-Rundles

    2005-01-01

    More than 120 inherited primary immunodeficiency diseases have been discovered in the past five decades, and the precise genetic defect in many of these diseases has now been identified. Increasing understanding of these molecular defects has considerably influenced both basic and translational research, and this has extended to many branches of medicine. Recent advances in both diagnosis and therapeutic modalities

  3. Recovery of Candida dubliniensis from Non-Human Immunodeficiency Virus-Infected Patients in Israel

    Microsoft Academic Search

    ITZHACK POLACHECK; JACOB STRAHILEVITZ; DEREK SULLIVAN; SAMANTHA DONNELLY; IRA F. SALKIN; DAVID C. COLEMAN

    2000-01-01

    Candida dubliniensis is a recently discovered yeast species principally associated with carriage and disease in the oral cavities of human immunodeficiency virus (HIV)-infected individuals. To date the majority of isolates of this species have been identified in Europe and North America. In this study, five Candida isolates recovered from separate HIV-negative hospitalized patients in Jerusalem, Israel, were presumptively identified as

  4. Chronic Granulomatous Disease: A Clinical Survey of 41 Patients from the Iranian Primary Immunodeficiency Registry

    Microsoft Academic Search

    Masoud Movahedi; Asghar Aghamohammadi; Nima Rezaei; Nikrad Shahnavaz; Ali Babaei Jandaghi; Abolhasan Farhoudi; Zahra Pourpak; Mostafa Moin; Mohammad Gharagozlou; Davoud Mansouri

    2004-01-01

    Background: Chronic granulomatous disease (CGD) represents a group of inherited disorders of the phagocytic system, involving recurrent infections at different sites, especially the respiratory system. The present study was accomplished in order to determine the clinical spectrum of Iranian patients with CGD. Methods: Forty-one patients (29 males and 12 females) with CGD, who had already been referred to two immunodeficiency

  5. Recombinant Glycoprotein Vaccines for Human Immunodeficiency Virus-Infected Children and Their Effects on Viral Quasispecies

    Microsoft Academic Search

    Shaffiq M. Essajee; Ram Yogev; Henry Pollack; Bryan Greenhouse; Keith Krasinski; William Borkowsky

    2002-01-01

    In individuals infected with human immunodeficiency virus type 1 (HIV-1), specific immunity is associated with a more diverse viral repertoire and slower disease progression. Attempts to enhance antiviral immunity with therapeutic vaccination have shown that recombinant glycoprotein (RGP) vaccines are safe, well tolerated, and immunogenic, but the effect of RGP vaccines on the viral repertoire is unknown. We evaluated diversifi-

  6. Erythrovirus B19 infection in acquired immunodeficiency syndrome: screening by histopathology, immunohistochemistry, and in situ hybridization

    Microsoft Academic Search

    Andréia Rodrigues; Cordovil Pires; Eliene Carvalho da Fonseca; Luiz Antônio Bastos Camacho; Jussara Pereira

    Erythrovirus B19 infects erythrocytic progenitors, transiently interrupting erythropoiesis. In AIDS patients it causes chronic anemia amenable to treatment. We looked for evidences of B19 infection in stored bone marrow material from patients with acquired immunodeficiency syndrome. Histological sections were made from stored paraffin blocks from 33 autopsies (39 blocks) and 35 biopsies (45 blocks, 30 patients) performed from 1988 to

  7. Nonviral and Viral Delivery of a Human Immunodeficiency Virus Protective Gene Into Primary Human T Cells

    Microsoft Academic Search

    Clive Woffendin; Zhi-Yong Yang; Udaykumar; Ling Xu; Ning-Sun Yang; Michael J. Sheehy; Gary J. Nabel

    1994-01-01

    Because AIDS has been refractory to traditional pharmacologic interventions, alternative approaches have been developed. Although the introduction of specific antiviral genes into T leukemia cells can provide relative resistance to human immunodeficiency virus (HIV) replication, the testing of such genes against primary viral isolates in human CD4^+ lymphocytes has been limited, and safety questions remain regarding gene delivery into cells

  8. Investigation of chronic diarrhoea in acquired immunodeficiency syndrome. A prospective study of 155 patients

    Microsoft Academic Search

    C Blanshard; N Francis; B G Gazzard

    1996-01-01

    BACKGROUND AND AIMS: The optimum diagnostic investigation for patients with acquired immunodeficiency syndrome (AIDS) and diarrhoea is not known. Often no pathogen is detected and it is unclear whether this is because pathogens are absent in some patients or the investigations used fail to detect them. The hypothesis that AIDS related diarrhoea is usually due to an infection, which can

  9. Immunization of children at risk of infection with human immunodeficiency virus

    Microsoft Academic Search

    William J. Moss; C. John Clements; Neal A. Halsey

    This paper reviews the English language literature on the safety, immunogenicity and effectiveness in children infected with the human immunodeficiency virus (HIV) of vaccines currently recommended by WHO for use in national immunization programmes. Immunization is generally safe and beneficial for children infected with HIV, although HIV-induced immune suppression reduces the benefit compared with that obtained in HIV-uninfected children. However,

  10. Prevalence of intestinal parasites in Cuban acquired immunodeficiency syndrome (AIDS) patients

    Microsoft Academic Search

    Angel Arturo Escobedo; Fidel Angel Núñez

    1999-01-01

    A coproparasitological study was carried out on 67 acquired immunodeficiency syndrome (AIDS) patients admitted at the Institute of Tropical Medicine ‘Pedro Kour??’. The results were compared with 136 HIV-seronegative patients (control group) who were also hospitalised in the same period. In both groups monoparasitism was more prevalent than polyparasitism and intestinal protozoa were more prevalent than helminths. At least one

  11. Efficient Isolation of Human Immunodeficiency Virus Type 1 RNA from Cervical Swabs

    Microsoft Academic Search

    ADELINE M. HAJJAR; PAUL F. LEWIS; YOHANNES ENDESHAW; JACKONIAH NDINYA-ACHOLA; JOAN K. KREISS; JULIE OVERBAUGH

    1998-01-01

    An efficient method for the isolation of human immunodeficiency virus type 1 (HIV-1) nucleic acids from dry cervical swabs was developed. HIV-1 gag and env were detected in 96% (25 of 26) and 81% (21 of 26), respectively, of the samples tested by PCR from HIV-1-seropositive women in a Kenyan cohort study. Eighty- eight percent of the swabs (22 of

  12. Development of an Instrument to Assess Nutritional Risk Factors for Children Infected with Human Immunodeficiency Virus

    Microsoft Academic Search

    LINDA HELLER; SARAH FOX; KIMBERLY J HELL; JOSEPH A CHURCH

    2000-01-01

    Objective To produce a simple and effective instrument to evaluate and monitor the nutritional risk of children infected with the human immunodeficiency virus (HIV).Design The test instrument was developed in consultation with 5 physicians, 5 nutritionists, and 5 social workers with expertise in caring for HIV-infected children. Patient information was collected through medical record review for 19 sociodemographic, 10 anthropometric,

  13. Toward an AIDS vaccine: lessons from natural simian immunodeficiency virus infections of African nonhuman primate hosts

    Microsoft Academic Search

    Donald L Sodora; Jonathan S Allan; Cristian Apetrei; Jason M Brenchley; Daniel C Douek; James G Else; Jacob D Estes; Beatrice H Hahn; Vanessa M Hirsch; Amitinder Kaur; Frank Kirchhoff; Michaela Muller-Trutwin; Ivona Pandrea; Jörn E Schmitz; Guido Silvestri

    2009-01-01

    The design of an effective AIDS vaccine has eluded the efforts of the scientific community to the point that alternative approaches to classic vaccine formulations have to be considered. We propose here that HIV vaccine research could greatly benefit from the study of natural simian immunodeficiency virus (SIV) infections of African nonhuman primates. Natural SIV hosts (for example, sooty mangabeys,

  14. Genetic characterization of simian immunodeficiency virus isolated from an African mandrill

    Microsoft Academic Search

    H. Sakai; J.-I. Sakuragi; S. Sakuragi; R. Shibata; M. Hayami; A. Ishimoto; A. Adachi

    1992-01-01

    Summary We constructed an infectious molecular clone of simian immunodeficiency virus from an African mandrill (SIVMND). Upon transfection, this clone directed the production of progeny virus particles infectious to and cytopathic for CD4+ human leukemia cells. Thirteen frameshift proviral mutants with an alteration in the eight open reading frames of SIVMND were generated by recombinant DNA techniques, and were analyzed

  15. Simian immunodeficiency virus from mandrill ( Mandrillus sphinx ) SIVmnd experimentally infects human and nonhuman primate cells

    Microsoft Academic Search

    Virginie Poaty-Mavoungou; Richard Onanga; Issa Bedjabaga; Elie Mavoungou

    2001-01-01

    This study set out to characterize the features of experimental infection by simian immunodeficiency virus in mandrill (SIVmnd) (Mandrillus sphinx), cynomolgus macaque (Macaca fascicularis), rhesus macaque (Macaca mulatta), chimpanzee (Pan troglodytes), African green monkey (Cercopithecus pygerythrus), baboon (Papio cynocephalus) and human cells. Purified cells were exposed to a primary isolate of SIVmnd grown in the infected mandrill peripheral blood mononuclear

  16. Lupus Manifestations in Severe Combined Immunodeficient (SCID) Mice and in Human\\/Mouse Radiation Chimeras

    Microsoft Academic Search

    Zev Sthoeger; Heidy Zinger; Benny Dekel; Fabian Arditi; Yair Reisner; Edna Mozes

    2003-01-01

    The objective of this study was to develop a human lupus model. To this end we have established and compared two models: (1) severe combined immunodeficient (SCID) mice reconstituted with peripheral blood lymphocytes (PBL) of either systemic lupus erythematosus (SLE) patients or healthy controls and (2) lethally irradiated BALB\\/c mice radioprotected with bone marrow of SCID mice, to which human

  17. Gas neutralizer flow field modeling and experiments

    NASA Astrophysics Data System (ADS)

    Martin, R. A.; Cline, M. C.; Muntz, E. P.; Farnham, T.

    1987-06-01

    A gas neutralizer internal flow field is computed using the Navier-Stokes code VNAP2 to assess the code's value as a gas neutralizer modeling tool and to provide design calculation. The steady-state, viscous, continuum field is produced by injecting argon gas radially into a cylindrical tube at the midplane. Inflow conditions are selected in accordance with design requirements to optimize the conversion of ions to neutral particles. Results from the calculations include the velocity field, contours of Mach number and density, axial and radial profiles of density, and axial profiles of the argon target thickness parameter. In addition, measurements inside a 1/3-scale gas neutralizer model are performed to benchmark the code. Density field measurements are obtained using the electron beam fluorescence technique, and limited pressure measurements are obtained from wall static pressure taps and a free molecular probe in the tube end. The code predictions are in reasonably good agreement with the experimental results showing that VNAP2 is useful for future gas neutralizer design calculations.

  18. Accelerating neutral atoms on a Table top

    NASA Astrophysics Data System (ADS)

    Krishnamurthy, M.; Rajendran, Rajeev; Madhu, T.; Kpm, Rishad; Narayanan, V.; Krishnakumar, E.

    2013-05-01

    Plasma accelerators driven by super strong laser fields couple unusually large energies to charged particles. Acceleration of neutral atoms from such strongly ionized plasmas have remained elusive. A laser based neutralizer can convert laser accelerated fast ion source to fast neutral atom source. We report a scheme to generate fast Argon atoms (up to 1 MeV) from an optical-field-ionized dense nano-cluster ensemble. Intense, ultrashort pulses ionize each atom in a Ar nanocluster to 8+ and coulomb explode ions to energies up to MeV. We show that in a dense cluster ensemble, the electrons that stream out of the focal volume collisionally excited clusters in the periphery of the focus to high lying Rydberg excited states and form a sheath of electronically excited clusters. Cross sections for reducing ions by charge transfer collisions are orders of magnitude larger with the electronically exited systems. Fast ions that stream through the excited cluster sheath are reduced to neutral atoms with no change in momentum. We show that the scheme can covert ions to neutral atoms with nearly 100% efficiency, transferring 8 electrons per atom in a few mm span of the supersonic jet.

  19. BEAMS3D Neutral Beam Injection Model

    NASA Astrophysics Data System (ADS)

    McMillan, Matthew; Lazerson, Samuel A.

    2014-09-01

    With the advent of applied 3D fields in Tokamaks and modern high performance stellarators, a need has arisen to address non-axisymmetric effects on neutral beam heating and fueling. We report on the development of a fully 3D neutral beam injection (NBI) model, BEAMS3D, which addresses this need by coupling 3D equilibria to a guiding center code capable of modeling neutral and charged particle trajectories across the separatrix and into the plasma core. Ionization, neutralization, charge-exchange, viscous slowing down, and pitch angle scattering are modeled with the ADAS atomic physics database. Elementary benchmark calculations are presented to verify the collisionless particle orbits, NBI model, frictional drag, and pitch angle scattering effects. A calculation of neutral beam heating in the NCSX device is performed, highlighting the capability of the code to handle 3D magnetic fields. Notice: this manuscript has been authored by Princeton University under Contract Number DE-AC02-09CH11466 with the US Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes.

  20. Color-Neutral Superconducting Quark Matter

    E-print Network

    Andrew W. Steiner; Sanjay Reddy; Madappa Prakash

    2002-09-29

    We investigate the consequences of enforcing local color neutrality on the color superconducting phases of quark matter by utilizing the Nambu-Jona-Lasinio model supplemented by diquark and the t'Hooft six-fermion interactions. In neutrino free matter at zero temperature, color neutrality guarantees that the number densities of u, d, and s quarks in the Color-Flavor-Locked (CFL) phase will be equal even with physical current quark masses. Electric charge neutrality follows as a consequence and without the presence of electrons. In contrast, electric charge neutrality in the less symmetric 2-flavor superconducting (2SC) phase with ud pairing requires more electrons than the normal quark phase. The free energy density cost of enforcing color and electric charge neutrality in the CFL phase is lower than that in the 2SC phase, which favors the formation of the CFL phase. With increasing temperature and neutrino content, an unlocking transition occurs from the CFL phase to the 2SC phase with the order of the transition depending on the temperature, the quark and lepton number chemical potentials. The astrophysical implications of this rich structure in the phase diagram, including estimates of the effects from Goldstone bosons in the CFL phase, are discussed.