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  • 1
    Online Resource
    Online Resource
    Acupuncture in the treatment of fatigue in Parkinson's disease: A pilot, randomized, controlled, study
    Wiley ; 2018
    In:  Brain and Behavior Vol. 8, No. 1 ( 2018-01)
    Details
    In: Brain and Behavior, Wiley, Vol. 8, No. 1 ( 2018-01)
    Abstract: Fatigue is a common and disabling problem in patients with Parkinson's disease ( PD ), and there is currently no satisfactory treatment. As acupuncture has been reported to be effective in fatigue related to other conditions, we sought to evaluate its efficacy in PD . Methods This was a single center, randomized, sham‐controlled study. Forty PD patients with moderately severe fatigue were randomized to receive 5 weeks of biweekly real or sham acupuncture. The primary outcome was change on the General Fatigue score of the Multidimensional Fatigue Inventory ( MFI ‐ GF ) at 5 weeks. Secondary outcomes included MFI ‐Total score, Unified Parkinson's Disease Rating Scale Motor score ( UPDRS Motor), Parkinson's Disease Questionnaire‐39 ( PDQ 39), Geriatrics Depression Scale ( GDS ), and Epworth Sleepiness Scale ESS ). All outcome measures were evaluated at baseline, 5 and 9 weeks. Results Both groups showed significant improvements in MFI ‐ GF and MFI ‐Total scores at 5 and 9 weeks, but there were no significant between‐group differences. There were no improvements from baseline for PDQ 39, GDS , and ESS . Although improvements were noted for the UPDRS Motor score in the real acupuncture group, no between‐group difference could be demonstrated. Conclusions Both real and sham acupuncture are equally effective in improving PD ‐related fatigue, and it is likely that this is due to nonspecific or placebo effects.
    Type of Medium: Online Resource
    ISSN: 2162-3279 , 2162-3279
    URL: Issue
    URL: Article
    DOI: 10.1002/brb3.2018.8.issue-1
    DOI: 10.1002/brb3.897
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2623587-0
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  • 2
    Online Resource
    Online Resource
    Inhibitors of protein and RNA synthesis block the cytotoxic effects of non-steroidal antiestrogens
    Elsevier BV ; 1995
    In:  Biochimica et Biophysica Acta (BBA) - Molecular Cell Research Vol. 1266, No. 2 ( 1995-04), p. 215-222
    Details
    In: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Elsevier BV, Vol. 1266, No. 2 ( 1995-04), p. 215-222
    Type of Medium: Online Resource
    ISSN: 0167-4889
    URL: Article
    DOI: 10.1016/0167-4889(95)00017-M
    RVK:
    WA 15000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1995
    detail.hit.zdb_id: 2209512-3
    SSG: 12
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  • 3
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    Availability of a Diversely Avid CD8+ T Cell Repertoire Specific for the Subdominant HLA-A2-Restricted HIV-1 Gag p2419–27 Epitope
    The American Association of Immunologists ; 2007
    In:  The Journal of Immunology Vol. 178, No. 12 ( 2007-06-15), p. 7756-7766
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 178, No. 12 ( 2007-06-15), p. 7756-7766
    Abstract: HLA-A2-restricted CTL responses to immunodominant HIV-1 epitopes do not appear to be very effective in the control of viral replication in vivo. In this study, we studied human CD8+ T cell responses to the subdominant HLA-A2-restricted epitope TV9 (Gag p2419–27, TLNAWVKVV) to explore the possibility of increasing its immune recognition. We confirmed in a cohort of 313 patients, infected by clade B or clade C viruses, that TV9 is rarely recognized. Of interest, the functional sensitivity of the TV9 response can be relatively high. The potential T cell repertoires for TV9 and the characteristics of constituent clonotypes were assessed by ex vivo priming of circulating CD8+ T cells from healthy seronegative donors. TV9-specific CTLs capable of suppressing viral replication in vitro were readily generated, suggesting that the cognate T cell repertoire is not limiting. However, these cultures contained multiple discrete populations with a range of binding avidities for the TV9 tetramer and correspondingly distinct functional dependencies on the CD8 coreceptor. The lack of dominant clonotypes was not affected by the stage of maturation of the priming dendritic cells. Cultures primed by dendritic cells transduced to present endogenous TV9 were also incapable of clonal maturation. Thus, a diffuse TCR repertoire appeared to be an intrinsic characteristic of TV9-specific responses. These data indicate that subdominance is not a function of poor immunogenicity, cognate TCR repertoire availability, or the potential avidity properties thereof, but rather suggest that useful responses to this epitope are suppressed by competing CD8+ T cell populations during HIV-1 infection.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.178.12.7756
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2007
    detail.hit.zdb_id: 1475085-5
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  • 4
    Online Resource
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    Generation of robust CD8+ T-cell responses against subdominant epitopes in conserved regions of HIV-1 by repertoire mining with mimotopes
    Wiley ; 2010
    In:  European Journal of Immunology Vol. 40, No. 7 ( 2010-07), p. 1950-1962
    Details
    In: European Journal of Immunology, Wiley, Vol. 40, No. 7 ( 2010-07), p. 1950-1962
    Type of Medium: Online Resource
    ISSN: 0014-2980
    URL: Article
    DOI: 10.1002/eji.200940079
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2010
    detail.hit.zdb_id: 1491907-2
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  • 5
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    Degeneracy and Repertoire of the Human HIV-1 Gag p1777–85 CTL Response
    The American Association of Immunologists ; 2006
    In:  The Journal of Immunology Vol. 176, No. 11 ( 2006-06-01), p. 6690-6701
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 176, No. 11 ( 2006-06-01), p. 6690-6701
    Abstract: CD8+ CTL responses are important for the control of HIV-1 infection. The immunodominant HLA-A2-restricted Gag epitope, SLYNTVATL (SL9), is considered to be a poor immunogen because reactivity to it is rare in acute infection despite its paradoxical dominance in patients with chronic infection. We have previously reported SL9 to be a help-independent epitope in that it primes highly activated CTLs ex vivo from CD8+ T cells of seronegative healthy donors. These CTLs produce sufficient cytokines for extended autocrine proliferation but are sensitive to activation-induced cell death, which may cause them to be eliminated by a proinflammatory cytokine storm. Here we identified an agonist variant of the SL9 peptide, p41 (SLYNTVAAL), by screening a large synthetic combinatorial nonapeptide library with ex vivo-primed SL9-specific T cells. p41 invariably immunized SL9-cross-reactive CTLs from other donors ex vivo and H-2Db β2m double knockout mice expressing a chimeric HLA-A*0201/H2-Db MHC class I molecule. Parallel human T cell cultures showed p41-specific CTLs to be less fastidious than SL9-CTLs in the level of costimulation required from APCs and the need for exogenous IL-2 to proliferate (help dependent). TCR sequencing revealed that the same clonotype can develop into either help-independent or help-dependent CTLs depending on the peptide used to activate the precursor CD8+ T cells. Although Ag-experienced SL9-T cells from two patients were also sensitive to IL-2-mediated cell death upon restimulation in vitro, the loss of SL9 T cells was minimized with p41. This study suggests that agonist sequences can replace aberrantly immunogenic native epitopes for the rational design of vaccines targeting HIV-1.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.176.11.6690
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2006
    detail.hit.zdb_id: 1475085-5
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  • 6
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    Primary Human Immunodeficiency Virus Type 1 (HIV-1) Infection during HIV-1 Gag Vaccination
    American Society for Microbiology ; 2008
    In:  Journal of Virology Vol. 82, No. 6 ( 2008-03-15), p. 2784-2791
    Details
    In: Journal of Virology, American Society for Microbiology, Vol. 82, No. 6 ( 2008-03-15), p. 2784-2791
    Abstract: Vaccination for human immunodeficiency virus type 1 (HIV-1) remains an elusive goal. Whether an unsuccessful vaccine might not only fail to provoke detectable immune responses but also could actually interfere with subsequent natural immunity upon HIV-1 infection is unknown. We performed detailed assessment of an HIV-1 gag DNA vaccine recipient (subject 00015) who was previously uninfected but sustained HIV-1 infection before completing a vaccination trial and another contemporaneously acutely infected individual (subject 00016) with the same strain of HIV-1. Subject 00015 received the vaccine at weeks 0, 4, and 8 and was found to have been acutely HIV-1 infected around the time of the third vaccination. Subject 00016 was a previously HIV-1-seronegative sexual contact who had symptoms of acute HIV-1 infection approximately 2 weeks earlier than subject 00015 and demonstrated subsequent seroconversion. Both individuals reached an unusually low level of chronic viremia ( 〈 1,000 copies/ml) without treatment. Subject 00015 had no detectable HIV-1-specific cytotoxic T-lymphocyte (CTL) responses until a borderline response was noted at the time of the third vaccination. The magnitude and breadth of Gag-specific CTL responses in subject 00015 were similar to those of subject 00016 during early chronic infection. Viral sequences from gag , pol , and nef confirmed the common source of HIV-1 between these individuals. The diversity and divergence of sequences in subjects 00015 and 00016 were similar, indicating similar immune pressure on these proteins (including Gag). As a whole, the data suggested that while the gag DNA vaccine did not prime detectable early CTL responses in subject 00015, vaccination did not appreciably impair his ability to contain viremia at levels similar to those in subject 00016.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    URL: Article
    DOI: 10.1128/JVI.01720-07
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2008
    detail.hit.zdb_id: 1495529-5
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  • 7
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    Online Resource
    HIV-1 Gag Cytotoxic T Lymphocyte Epitopes Vary in Presentation Kinetics Relative to HLA Class I Downregulation
    American Society for Microbiology ; 2013
    In:  Journal of Virology Vol. 87, No. 15 ( 2013-08), p. 8726-8734
    Details
    In: Journal of Virology, American Society for Microbiology, Vol. 87, No. 15 ( 2013-08), p. 8726-8734
    Abstract: Although CD8 + cytotoxic T lymphocytes (CTLs) are protective in HIV-1 infection, the factors determining their antiviral efficiency are poorly defined. It is proposed that Gag targeting is superior because of very early Gag epitope presentation, allowing early killing of infected cells before Nef-mediated downregulation of human leukocyte antigen class I (HLA-I). To study Gag epitope presentation kinetics, three epitopes (SL9 77-85 , KF11 162-172 , and TW10 240-249 ) were genetically translocated from their endogenous location in the Rev-dependent (late) gag gene into the Rev-independent (early) nef gene with concomitant mutation of the corresponding endogenous epitopes to nonrecognized sequences. These viruses were compared to the index virus for CTL-mediated suppression of replication and the susceptibility of this antiviral activity to Nef-mediated HLA-I downregulation. SL9-specific CTLs gained activity after SL9 translocation to Nef, going from Nef sensitive to Nef insensitive, indicating that translocation accelerated infected cell recognition from after to before HLA-I downregulation. KF11-specific CTL antiviral activity was unchanged and insensitive to HLA-I downregulation before and after KF11 translocation, suggesting that already rapid recognition of infected cells was not accelerated. However, TW10-specific CTLs that were insensitive to Nef at the baseline became sensitive with reduced antiviral activity after translocation, indicating that translocation retarded epitope expression. Cytosolic peptide processing assays suggested that TW10 was inefficiently generated after translocation to Nef, compared to SL9 and KF11. As a whole, these data demonstrate that epitope presentation kinetics play an important role in CTL antiviral efficiency, that Gag epitopes are not uniformly presented early, and that the epitope context can play a major role in presentation kinetics.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    URL: Article
    DOI: 10.1128/JVI.01040-13
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2013
    detail.hit.zdb_id: 1495529-5
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  • 8
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    Online Resource
    Differential immunogenicity of vaccinia and HIV-1 components of a human recombinant vaccine in mucosal and blood compartments
    Elsevier BV ; 2008
    In:  Vaccine Vol. 26, No. 35 ( 2008-8), p. 4617-4623
    Details
    In: Vaccine, Elsevier BV, Vol. 26, No. 35 ( 2008-8), p. 4617-4623
    Type of Medium: Online Resource
    ISSN: 0264-410X
    URL: Article
    DOI: 10.1016/j.vaccine.2008.05.084
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2008
    detail.hit.zdb_id: 1468474-3
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  • 9
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    Online Resource
    HIV-1 Epitope Variability Is Associated with T Cell Receptor Repertoire Instability and Breadth
    American Society for Microbiology ; 2017
    In:  Journal of Virology Vol. 91, No. 16 ( 2017-08-15)
    Details
    In: Journal of Virology, American Society for Microbiology, Vol. 91, No. 16 ( 2017-08-15)
    Abstract: Mutational escape of HIV-1 from HIV-1-specific CD8 + T lymphocytes (CTLs) is a major barrier for effective immune control. Each epitope typically is targeted by multiple clones with distinct T cell receptors (TCRs). While the clonal repertoire may be important for containing epitope variation, determinants of its composition are poorly understood. We investigate the clonal repertoire of 29 CTL responses against 23 HIV-1 epitopes longitudinally in nine chronically infected untreated subjects with plasma viremia of 〈 3,000 RNA copies/ml over 17 to 179 weeks. The composition of TCRs targeting each epitope varied considerably in stability over time, although clonal stability (Sorensen index) was not significantly time dependent within this interval. However, TCR stability inversely correlated with epitope variability in the Los Alamos HIV-1 Sequence Database, consistent with TCR evolution being driven by epitope variation. Finally, a robust inverse correlation of TCR breadth against each epitope versus epitope variability further suggested that this variability drives TCR repertoire diversification. In the context of studies demonstrating rapidly shifting HIV-1 sequences in vivo , our findings support a variably dynamic process of shifting CTL clonality lagging in tandem with viral evolution and suggest that preventing escape of HIV-1 may require coordinated direction of the CTL clonal repertoire to simultaneously block escape pathways. IMPORTANCE Mutational escape of HIV-1 from HIV-1-specific CD8 + T lymphocytes (CTLs) is a major barrier to effective immune control. The number of distinct CTL clones targeting each epitope is proposed to be an important factor, but the determinants are poorly understood. Here, we demonstrate that the clonal stability and number of clones for the CTL response against an epitope are inversely associated with the general variability of the epitope. These results show that CTLs constantly lag epitope mutation, suggesting that preventing HIV-1 escape may require coordinated direction of the CTL clonal repertoire to simultaneously block escape pathways.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    URL: Article
    DOI: 10.1128/JVI.00771-17
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2017
    detail.hit.zdb_id: 1495529-5
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  • 10
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    Online Resource
    Epitope-Dependent Avidity Thresholds for Cytotoxic T-Lymphocyte Clearance of Virus-Infected Cells
    American Society for Microbiology ; 2007
    In:  Journal of Virology Vol. 81, No. 10 ( 2007-05-15), p. 4973-4980
    Details
    In: Journal of Virology, American Society for Microbiology, Vol. 81, No. 10 ( 2007-05-15), p. 4973-4980
    Abstract: Cytotoxic T lymphocytes (CTLs) are crucial for immune control of viral infections. “Functional avidity,” defined by the sensitizing dose of exogenously added epitope yielding half-maximal CTL triggering against uninfected target cells (SD 50 ), has been utilized extensively as a measure of antiviral efficiency. However, CTLs recognize infected cells via endogenously produced epitopes, and the relationship of SD 50 to antiviral activity has never been directly revealed. We elucidate this relationship by comparing CTL killing of cells infected with panels of epitope-variant viruses to the corresponding SD 50 for the variant epitopes. This reveals a steeply sigmoid relationship between avidity and infected cell killing, with avidity thresholds (defined as the SD 50 required for CTL to achieve 50% efficiency of infected cell killing [KE 50 ]), below which infected cell killing rapidly drops to none and above which killing efficiency rapidly plateaus. Three CTL clones recognizing the same viral epitope show the same KE 50 despite differential recognition of individual epitope variants, while CTLs recognizing another epitope show a 10-fold-higher KE 50 , demonstrating epitope dependence of KE 50 . Finally, the ability of CTLs to suppress viral replication depends on the same threshold KE 50 . Thus, defining KE 50 values is required to interpret the significance of functional avidity measurements and predict CTL efficacy against virus-infected cells in pathogenesis and vaccine studies.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    URL: Article
    DOI: 10.1128/JVI.02362-06
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2007
    detail.hit.zdb_id: 1495529-5
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