96 results on '"Jagodzinski L"'
Search Results
2. Development of a sensitive, quantitative assay with broad subtype specificity for detection of total HIV-1 nucleic acids in plasma and PBMC
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Kibirige, C. N., Manak, M., King, D., Abel, B., Hack, H., Wooding, D., Liu, Y., Fernandez, N., Dalel, J., Kaye, Steve, Imami, N., Jagodzinski, L., and Gilmour, J.
- Published
- 2022
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3. Late Palaeoproterozoic evolution of the buried northern Gawler Craton
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Armit, R., Betts, P.G., Schaefer, B.F., Yi, K., Kim, Y., Dutch, R.A., Reid, A., Jagodzinski, L., Giles, D., and Ailleres, L.
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- 2017
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4. Genetic Variability between Isolates of Human Immunodeficiency Virus (HIV) Type 2 is Comparable to the Variability among HIV Type 1
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Zagury, J. F., Franchini, G., Reitz, M., Collalti, E., Starcich, B., Hall, L., Fargnoli, K., Jagodzinski, L., Laure, F., Arya, S. K., Josephs, S., Zagury, D., Wong-Staal, F., and Gallo, R. C.
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- 1988
5. Changes in antioxidant status in patients with ankylosing spondylitis during cryotherapy: 61
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Stanek, A., Cieślar, G., Matyszkiewicz, B., Rozmus-Kuczia, I., Romuk, E., Skrzep-Poloczek, B., Birkner, E., Jagodzinski, L., and Sieroń, A.
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- 2006
6. Complete Nucleotide Sequences of Functional Clones of the Virus Associated with the Acquired Immunodeficiency Syndrome, HTLV-III/LAV
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Ratner, L., Fisher, A., Jagodzinski, L. L., Liou, R.-S., Mitsuya, H., Gallo, R. C., Wong-Staal, F., Heimpel, H., editor, Huhn, D., editor, Mueller-Eckhardt, C., editor, Ruhenstroth-Bauer, G., editor, Neth, Rolf, editor, Gallo, Robert C., editor, Greaves, Melvyn F., editor, and Kabisch, Hartmut, editor
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- 1987
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7. Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection
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Sailasuta, N, Ross, W, Ananworanich, J, Chalermchai, T, DeGruttola, V, Lerdlum, S, Pothisri, M, Busovaca, E, Ratto-Kim, S, Jagodzinski, L, Spudich, S, Michael, N, Kim, JH, Valcour, V, Phanuphak, N, Teeratakulpisarn, N, Fletcher, JLK, Suttichom, D, Pinyakorn, S, Rattanamanee, S, Chomchey, N, Mangum, P, Ubolyam, S, Suwanwela, NC, Chaisinanunkul, N, Suthiponpaisan, U, Sutthapas, C, deSouza, M, Ngauy, V, Trichavaroj, R, Akapirat, S, Marovich, M, Wendelken, L, Liu, C, Mun, E, and Miller, B
- Abstract
Objective: Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART). Methods: Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART. Results: After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months. Interpretation: We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury. © 2012 Sailasuta et al.
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- 2012
8. Central nervous system viral invasion and inflammation during acute HIV infection
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Valcour, V, Chalermchai, T, Sailasuta, N, Marovich, M, Lerdlum, S, Suttichom, D, Suwanwela, NC, Jagodzinski, L, Michael, N, Spudich, S, van Griensven, F, de Souza, M, Kim, J, Ananworanich, J, and RV254/SEARCH 010 Study Group
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Inflammation ,Adult ,Male ,Young Adult ,Central Nervous System Infections ,RV254/SEARCH 010 Study Group ,Acute Disease ,Humans ,RNA, Viral ,HIV Infections ,Female ,Middle Aged ,Magnetic Resonance Imaging - Abstract
Understanding the earliest central nervous system (CNS) events during human immunodeficiency virus (HIV) infection is crucial to knowledge of neuropathogenesis, but these have not previously been described in humans.Twenty individuals who had acute HIV infection (Fiebig stages I-IV), with average 15 days after exposure, underwent clinical neurological, cerebrospinal fluid (CSF), magnetic resonance imaging, and magnetic resonance spectroscopy (MRS) characterization.HIV RNA was detected in the CSF from 15 of 18 subjects as early as 8 days after estimated HIV transmission. Undetectable CSF levels of HIV (in 3 of 18) was noted during Fiebig stages I, II, and III, with plasma HIV RNA levels of 285651, 2321, and 81978 copies/mL, respectively. On average, the CSF HIV RNA level was 2.42 log(10) copies/mL lower than that in plasma. There were no cases in which the CSF HIV RNA level exceeded that in plasma. Headache was common during the acute retroviral syndrome (in 11 of 20 subjects), but no other neurological signs or symptoms were seen. Intrathecal immune activation was identified in some subjects with elevated CSF neopterin, monocyte chemotactic protein/CCL2, and interferon γ-induced protein 10/CXCL-10 levels. Brain inflammation was suggested by MRS.CSF HIV RNA was detectable in humans as early as 8 days after exposure. CNS inflammation was apparent by CSF analysis and MRS in some individuals during acute HIV infection.
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- 2012
9. 641Acute Retroviral Syndrome is Associated with Gut Mucosal CD4 Depletion, Inflammation and High Viral and Proviral Burden in Systemic and Tissue Compartments
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Jagodzinski L, Eugene Kroon, Rattanamanee S, Valcour, Rapee Trichavaroj, Merlin L. Robb, Serena Spudich, Jintanat Ananworanich, Nelson L. Michael, Rungsun Rerknimitr, Krebs S, Jerome H. Kim, Irini Sereti, James L. K. Fletcher, Robin L. Dewar, Netanya G. Sandler, Trevor A Crowell, Suteeraporn Pinyakorn, Chomont N, Alexandra Schuetz, Nittaya Phanuphak, and Slike B
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IDWeek 2014 Abstracts ,Infectious Diseases ,Text mining ,Oncology ,Oral Abstracts ,business.industry ,Immunology ,Medicine ,Inflammation ,medicine.symptom ,business - Published
- 2014
10. P284 Prospective multicenter trial of tigecycline for treatment of central venous catheter (CVC)-related coagulase-negative staphylococcal (CoNS) bacteremia
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Maki, D., primary, Lentnek, A., additional, Sheftel, T., additional, Paladino, J., additional, Feuerstein, S., additional, Jagodzinski, L., additional, and Schentag, J., additional
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- 2009
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11. Tectonic Framework and Evolution of the Gawler Craton, Southern Australia
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Hand, M., primary, Reid, A., additional, and Jagodzinski, L., additional
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- 2007
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12. In-Depth Analysis of a Heterosexually Acquired Human Immunodeficiency Virus Type 1 Superinfection: Evolution, Temporal Fluctuation, and Intercompartment Dynamics from the Seronegative Window Period through 30 Months Postinfection
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McCutchan, F. E., primary, Hoelscher, M., additional, Tovanabutra, S., additional, Piyasirisilp, S., additional, Sanders-Buell, E., additional, Ramos, G., additional, Jagodzinski, L., additional, Polonis, V., additional, Maboko, L., additional, Mmbando, D., additional, Hoffmann, O., additional, Riedner, G., additional, von Sonnenburg, F., additional, Robb, M., additional, and Birx, D. L., additional
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- 2005
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13. Allergic contact dermatitis from topical corticosteroid preparations
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JAGODZINSKI, L, primary
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- 1995
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14. Identification of the human herpesvirus 6 glycoprotein H and putative large tegument protein genes
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Josephs, S F, primary, Ablashi, D V, additional, Salahuddin, S Z, additional, Jagodzinski, L L, additional, Wong-Staal, F, additional, and Gallo, R C, additional
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- 1991
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15. Persistent infection of rhesus macaques with a molecular clone of human immunodeficiency virus type 2: evidence of minimal genetic drift and low pathogenetic effects
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Franchini, G, primary, Markham, P, additional, Gard, E, additional, Fargnoli, K, additional, Keubaruwa, S, additional, Jagodzinski, L, additional, Robert-Guroff, M, additional, Lusso, P, additional, Ford, G, additional, and Wong-Staal, F, additional
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- 1990
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16. Structure of simian immunodeficiency virus regulatory genes.
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Colombini, S, Arya, S K, Reitz, M S, Jagodzinski, L, Beaver, B, and Wong-Staal, F
- Abstract
Three full-length cDNA clones were obtained from cells infected with the simian immunodeficiency virus (SIV) isolated from captive macaques (SIVMAC). Nucleotide sequence analyses suggested that these represented mRNA for the SIV MAC genes tat, rev (formerly, art/trs), and nef (formerly, 3'orf). The putative tat-specific clone was active in trans-activation of the SIV MAC long terminal repeat in COS-1 and Jurkat cells. In contrast, the human immunodeficiency virus 1 long terminal repeat was significantly trans-activated only in the COS-1 cells. This suggests that trans-activation by the SIV tat gene is modulated by cell-specific factors. The structure of all of the clones suggested an mRNA splicing pattern more complex than that described for human immunodeficiency virus 1.
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- 1989
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17. Molecular and biological characterization of a replication competent human immunodeficiency type 2 (HIV-2) proviral clone.
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Franchini, G, Fargnoli, K A, Giombini, F, Jagodzinski, L, De Rossi, A, Bosch, M, Biberfeld, G, Fenyo, E M, Albert, J, and Gallo, R C
- Abstract
We obtained complete genomic clones of human immunodeficiency virus type 2 (HIV-2) from the DNA of the neoplastic human cell line HUT 78 freshly infected with a HIV-2 isolate, strain SBL6669. The recombinant phage DNA was transfected into the lymphocytes of CD4-positive HUT 78 cell line to test the replication competence of the proviral DNA. One genomic clone, designated HIV-2SBL/ISY, yielded retroviral particles after a few weeks of culture of the transfected cells. The HIV-2SBL/ISY clone contained a complete provirus and cellular flanking sequence. We obtained the DNA sequence of the provirus and compared it with the published sequence of two other HIV-2 isolates. The degree of variability among HIV-2 isolates is comparable to that observed among African HIV-1 isolates sequenced to date. Immunologically, HIV-2SBL/ISY is similar to the parental virus (HIV-2SBL6669) but differs in the envelope transmembrane protein that is truncated (gp32-34) in the parental virus and not in HIV-2SBL/ISY (gp41). Both the parental and the cloned viruses are infectious and cytopathic for some human T-cell lines, induce syncytia, and infect a human macrophage cell line (U937) in vitro. The availability of a biologically active HIV-2 clone provides the means to study the role and interaction of HIV-2 genes in vitro as well as to assess the functional similarities among HIV-1 and HIV-2 genes. Since HIV-2SBL/ISY cloned virus infects fresh peripheral blood T cells from Rhesus macaques in vitro and infects the same animal in vivo, its use in animals may represent a model for functional study of viral genes in vivo as well as for development of experimental approaches to prevent and cure retroviral infection in humans.
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- 1989
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18. Fine structure and evolution of the rat serum albumin gene
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Sargent, T D, Jagodzinski, L L, Yang, M, and Bonner, J
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The exons, their boundaries, and approximately half of the intronic deoxyribonucleic acid of the rat serum albumin gene were sequenced. In addition to the 14 exons identified earlier by R-loop analysis, a small exon was detected between the "leader" exon (Z) and exon B. The leader exon encoded the 5'-untranslated portion of albumin messenger ribonucleic acid and the "pre-pro" oligopeptide present on the nascent protein. The sites of initiation and termination of transcription were tentatively identified by comparison of the 5' and 3' gene-flanking sequences with those of other eucaryotic genes. All 28 intron/exon junctions conformed to the "GT-AG rule" (Breathnach et al., Proc. Natl. Acad. Sci. 75:4853-4857, 1978). The three homologous domains of albumin were encoded by three subgenes that consisted of four exons each and evolved by intragenic duplication of a common ancestor. The second and forth exons of each subgene appeared to be the result of an even earlier duplication event. We propose a model for the evolution of this gene that accounts for the observed patterns of exon size and homology.
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- 1981
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19. Sequence homology between RNAs encoding rat alpha-fetoprotein and rat serum albumin.
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Jagodzinski, L L, Sargent, T D, Yang, M, Glackin, C, and Bonner, J
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We have determined the sequences of the recombinant DNA inserts of three bacterial plasmid cDNA clones containing most of the rat alpha a-fetoprotein mRNA. The resultant nucleotide sequence of alpha-fetoprotein was exhaustively compared to the nucleotide sequence of the mRNA encoding rat serum albumin. These two mRNAs have extensive homology (50%) throughout and the same intron locations. The amino acid sequence of rat alpha-fetoprotein has been deduced from the nucleotide sequence, and its comparison to rat serum albumin's amino acid sequence reveals a 34% homology. The regularly spaced positions of the cysteines found in serum albumin are conserved in rat alpha-fetoprotein, indicating that these two proteins may have a similar secondary folding structure. These homologies indicate that alpha-fetoprotein and serum albumin were derived by duplication of a common ancestral gene and constitute a gene family.
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- 1981
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20. Activation of a novel KpnI transcript by downstream integration of a human T-lymphotropic virus type I provirus.
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Okamoto, T, Reitz, M S, Clarke, M F, Jagodzinski, L L, and Wong-Staal, F
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A cDNA library was constructed from the HUT102 cell line established from a patient with adult T-cell leukemia/lymphoma and screened for cDNA clones that contain (i) cellular sequences abundantly expressed in HUT102 cells and not in the virus-negative T-cell line HUT78, and (ii) viral long terminal repeat (LTR) sequences either in the 5‘ end or in the 3‘ end. One such cDNA clone, KT1, was isolated and its nucleotide sequence was determined. It contains three regions: a KpnI repeat, a unique cellular region (UCR), and the U3 + R sequence of the human T-lymphotropic virus type I LTR. The arrangement of this clone suggests that its RNA transcript was activated by provirus integration in cis, possibly by the activity of a downstream provirus enhancer. Analysis of HUT102 DNA shows that one allele of the KT1 UCR is rearranged. The expression of the KT1 UCR is unique to HUT102. These data are consistent with the idea that the human T-lymphotropic virus type I LTR contains an enhancer which can activate upstream sequences in cis. The possible significance of this finding is discussed.
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- 1986
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21. Influence of low temperature on lymph formation and lymph flow velocity in mice
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Sieron, A., Pastuszka, A., Marniok, B., Wisniowska, B., Jagodzinski, L., Slusarczyk, K., Grzegorz Cieslar, and Stanek, A.
22. Prediction of disease progression in CPCRA 007: the role of unintegrated HIV DNA (UDNA) and HIV RNA
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Donovan, R., Mayers, D., Bush, C., Jagodzinski, L., Weislow, O., Baxa, D., Winslow, D., Collins, G., Hodges, J., Reves, R., and Saravolatz, L.
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HIV infection -- Development and progression - Published
- 1996
23. Safety and immunogenicity of a randomized phase I prime-boost trial with ALVAC-HIV (vCP205) and gp160 MN/LAI-2 adjuvanted in alum or polyphosphazene
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O'Connell RJ, Polonis VR, Ratto-Kim S, Cox J, Jagodzinski LL, Malia J, Michael NL, Excler J, Robb ML, and Kim JH
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2012
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24. Cross-sectional assessment of prevalence and correlates of blood-borne and sexually-transmitted infections among Afghan National Army recruits
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Todd Catherine S, Nasir Abdul, Mansoor G, Sahibzada Sayed M, Jagodzinski Linda L, Salimi Farzana, Khateri M, Hale Braden R, Barthel R, and Scott Paul T
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Afghanistan ,Military populations ,HIV ,Sexual risk behavior ,Drug use ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Few data are available in Afghanistan to shape national military force health practices, particularly with regard to sexually-transmitted infections (STIs). We measured prevalence and correlates of HIV, syphilis, herpes simplex 2 virus (HSV-2), and hepatitis C virus (HCV) among Afghan National Army (ANA) recruits. Methods A cross-sectional sample of male ANA recruits aged 18–35 years were randomly selected at the Kabul Military Training Center between February 2010 and January 2011. Participants completed an interviewer-administered questionnaire and serum-based rapid testing for syphilis and hepatitis C virus antibody on-site; HIV and HSV-2 screening, and confirmatory testing were performed off-site. Prevalence of each infection was calculated and logistic regression analysis performed to identify correlates. Results Of 5313 recruits approached, 4750 consented to participation. Participants had a mean age of 21.8 years (SD±3.8), 65.5% had lived outside Afghanistan, and 44.3% had no formal education. Few reported prior marijuana (16.3%), alcohol (5.3%), or opiate (3.4%) use. Of sexually active recruits (58.7%, N = 2786), 21.3% reported paying women for sex and 21.3% reported sex with males. Prevalence of HIV (0.063%, 95% CI: 0.013- 0.19), syphilis (0.65%, 95% CI: 0.44 – 0.93), and HCV (0.82%, 95% CI: 0.58 – 1.12) were quite low. Prevalence of HSV-2 was 3.03% (95% CI: 2.56 - 3.57), which was independently associated with age (Adjusted Odds Ratio (AOR) = 1.04, 95% CI: 1.00 - 1.09) and having a television (socioeconomic marker) (AOR = 1.46, 95% CI: 1.03 – 2.05). Conclusion Though prevalence of HIV, HCV, syphilis, and HSV-2 was low, sexual risk behaviors and intoxicant use were present among a substantial minority, indicating need for prevention programming. Formative work is needed to determine a culturally appropriate approach for prevention programming to reduce STI risk among Afghan National Army troops.
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- 2012
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25. Late Palaeoproterozoic evolution of the buried northern Gawler Craton
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Anthony Reid, Peter G Betts, David Giles, Robin Armit, Laurent Ailleres, Bruce F. Schaefer, K Yi, Rian Dutch, Young J. Kim, Liz Jagodzinski, Armit, R, Betts, PG, Schaefer, BF, Yi, K, Kim, Y, Dutch, RA, Reid, A, Jagodzinski, L, Giles, D, and Ailleres, L
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geography ,Provenance ,U-Pb geochronology ,in-situ zircon Lu-Hf isotopes ,geography.geographical_feature_category ,010504 meteorology & atmospheric sciences ,Nawa Domain ,Geochemistry ,Metamorphism ,Geology ,Orogeny ,010502 geochemistry & geophysics ,Anatexis ,Whole-rock Nd-Hf-isotopes ,01 natural sciences ,Craton ,Geochemistry and Petrology ,Geochronology ,Sedimentary rock ,Gawler Craton ,0105 earth and related environmental sciences ,Zircon - Abstract
This study utilises U-Pb geochronology, Lu-Hf, Sm-Nd isotopes and geochemistry to constrain the timing of deposition, metamorphism and provenance characteristics of buried Palaeoproterozoic meta-sedimentary and meta-igneous rocks in the northern Gawler Craton, Australia. The data suggest that sedimentary sequences were deposited between ca. 1780 and 1740 Ma across a wide region accompanied by syn-depositional magmatism. Restricted zircon age spectra, relatively radiogenic whole-rock Hf-Nd and in-situ zircon Hf isotopic compositions and enriched REE signatures support the notion of a connected series of basins or a single large basin, which developed on a common Neoarchaean substrate across the northern Gawler Craton during the Late Palaeoproterozoic. Temporal and isotopic correlation of these indurated rocks with Palaeoproterozoic basins throughout the North Australian Craton suggests they may form part of an extensive basin system that developed across the Australian continent during the Late Palaeoproterozoic. The meta-sedimentary and meta-igneous rocks of the northern Gawler Craton record high-grade crustal anatexis during the ca. 1730–1690 Ma Kimban Orogeny and subsequent Early Mesoproterozoic re-working. Refereed/Peer-reviewed
- Published
- 2017
26. Cerebrospinal fluid pleocytosis is associated with HIV-1 neuroinvasion during acute infection.
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Chan P, Moreland S, Sacdalan C, Kroon E, Colby D, Sriplienchan S, Pinyakorn S, Phanuphak N, Jagodzinski L, Valcour V, Vasan S, Paul R, Trautmann L, and Spudich S
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- Male, Humans, Female, Leukocytosis, RNA, Viral, Viral Load, Cerebrospinal Fluid, HIV Infections complications, HIV-1 genetics, HIV Seropositivity complications
- Abstract
Objective: HIV-1 invades the brain within days post-transmission. This study quantitated cerebrospinal fluid (CSF) white blood cell count (WBC) and investigated whether it associated with plasma and CSF HIV-1 RNA during untreated acute HIV infection (AHI)., Design: Seventy participants underwent lumbar puncture during Fiebig stages I-V AHI., Method: WBC and HIV-1 RNA with a lower limit of quantification (LLQ) of 80 copies/ml were measured in CSF., Results: Sixty-nine (99%) participants were men, with a median age of 26. Their blood CD4 + and CD8 + T-cell counts were 335 [interquartile range (IQR) 247-553) and 540 (IQR 357-802) cells/μl, respectively. Forty-five (64%) were in Fiebig stages III-V whereas 25 (36%) were in Feibig stages I-II. Fifty-two (74%) experienced acute retroviral syndrome. Median plasma and CSF HIV-1 RNA were 6.10 (IQR 5.15-6.78) and 3.15 (IQR 1.90-4.11) log 10 copies/ml, respectively. Sixteen (23%) CSF samples had HIV-1 RNA below LLQ. Median CSF WBC was 2.5 (IQR 1-8) cells/μl. CSF pleocytosis (WBC >5) was observed in 33% and was only present in CSF samples with detectable HIV-1 RNA. The frequencies of CSF pleocytosis during Fiebig stages III-V and among CSF samples of higher viral load (>1000 copies/ml) were 42 and 45%, respectively. Pleocytosis independently associated with CSF HIV-1 RNA in multivariate analysis [adjusted coefficient: 0.79, 95% confidence interval (CI) 0.41-1.14), P < 0.001] and a lower plasma to CSF HIV-1 RNA ratio ( P < 0.001)., Conclusion: CSF pleocytosis was present in one-third of participants with AHI. It associated with higher CSF HIV-1 RNA and a lower plasma to CSF HIV-1 RNA ratio, suggesting a potential association with HIV-1 neuroinvasion., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2024
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27. A systematic scoping review on the evidence behind debriefing practices for the wellbeing/emotional outcomes of healthcare workers.
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Evans TR, Burns C, Essex R, Finnerty G, Hatton E, Clements AJ, Breau G, Quinn F, Elliott H, Smith LD, Matthews B, Jennings K, Crossman J, Williams G, Miller D, Harold B, Gurnett P, Jagodzinski L, Smith J, Milligan W, Markowski M, Collins P, Yoshimatsu Y, Margalef Turull J, Colpus M, Dayson ML, and Weldon S
- Abstract
Introduction: Debriefings give healthcare workers voice through the opportunity to discuss unanticipated or difficult events and recommend changes. The typical goal of routine debriefings has been to improve clinical outcomes by learning through discussion and reflection of events and then transferring that learning into clinical practice. However, little research has investigated the effects of debriefings on the emotional experiences and well-being of healthcare workers. There is some evidence that debriefings are a multi-faceted and cost-effective intervention for minimising negative health outcomes, but their use is inconsistent and they are infrequently adopted with the specific intention of giving healthcare workers a voice. The purpose of this systematic scoping review is therefore to assess the scope of existing evidence on debriefing practices for the well-being and emotional outcomes of healthcare workers., Methods: Following screening, 184 papers were synthesised through keyword mapping and exploratory trend identification., Results: The body of evidence reviewed were clustered geographically, but diverse on many other criteria of interest including the types of evidence produced, debriefing models and practices, and outcomes captured., Discussion: The current review provides a clear map of our existing understanding and highlights the need for more systematic, collaborative and rigorous bodies of evidence to determine the potential of debriefing to support the emotional outcomes of those working within healthcare., Systematic Review Registration: https://osf.io/za6rj., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Evans, Burns, Essex, Finnerty, Hatton, Clements, Breau, Quinn, Elliott, Smith, Matthews, Jennings, Crossman, Williams, Miller, Harold, Gurnett, Jagodzinski, Smith, Milligan, Markowski, Collins, Yoshimatsu, Margalef Turull, Colpus, Dayson and Weldon.)
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- 2023
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28. Minimal detection of cerebrospinal fluid escape after initiation of antiretroviral therapy in acute HIV-1 infection.
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Handoko R, Chan P, Jagodzinski L, Pinyakorn S, Ubolyam S, Phanuphak N, Sacdalan C, Kroon E, Dumrongpisutikul N, Paul R, Valcour V, Ananworanich J, Vasan S, and Spudich S
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- Anti-Retroviral Agents therapeutic use, Cerebrospinal Fluid, Humans, Prospective Studies, RNA, Viral, Thailand, Viral Load, HIV Infections drug therapy, HIV-1 genetics
- Abstract
Objective: Despite suppression of HIV-1 replication in the periphery by antiretroviral therapy (ART), up to 10% of treated individuals have quantifiable HIV-1 in the CSF, termed CSF escape. CSF escape may be asymptomatic but has also been linked to progressive neurological disease, and may indicate persistence of HIV in the central nervous system (CNS). CSF escape has not yet been assessed after initiation of ART during acute HIV-1 infection (AHI)., Design: Prospective cohort study., Setting: Major voluntary counseling and testing site in Bangkok, Thailand., Participants: Participants identified and initiated on ART during AHI who received an optional study lumbar puncture at pre-ART baseline or after 24 or 96 weeks of ART., Main Outcome Measures: Paired levels of CSF and plasma HIV-1 RNA, with CSF greater than plasma HIV-1 RNA defined as CSF escape., Results: Two hundred and four participants had paired blood and CSF sampling in at least one visit at baseline, week 24, or week 96. Twenty-nine participants had CSF sampling at all three visits. CSF escape was detected in 1/90 at week 24 (CSF HIV-1 RNA 2.50 log10 copies/ml, plasma HIV-1 RNA <50 copies/ml), and 0/55 at week 96., Conclusion: Although levels of CSF HIV-1 RNA in untreated AHI are high, initiating treatment during AHI results in a very low rate of CSF escape in the first 2 years of treatment. Early treatment may improve control of HIV-1 within the CNS compared with treatment during chronic infection, which may have implications for long-term neurological outcomes and CNS HIV-1 persistence., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2021
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29. Regional brain volumetric changes despite 2 years of treatment initiated during acute HIV infection.
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Kallianpur KJ, Jahanshad N, Sailasuta N, Benjapornpong K, Chan P, Pothisri M, Dumrongpisutikul N, Laws E, Ndhlovu LC, Clifford KM, Paul R, Jagodzinski L, Krebs S, Ananworanich J, Spudich S, and Valcour V
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- Adult, Humans, Magnetic Resonance Imaging, Male, Organ Size, Prospective Studies, Thailand, Young Adult, Brain anatomy & histology, Brain diagnostic imaging, HIV Infections complications, HIV Infections drug therapy
- Abstract
Objective: To assess changes in regional brain volumes after 24 months among individuals who initiated combination antiretroviral therapy (cART) within weeks of HIV exposure., Design: Prospective cohort study of Thai participants in the earliest stages of HIV-1infection., Methods: Thirty-four acutely HIV-infected individuals (AHI; Fiebig I-V) underwent brain magnetic resonance (MR) imaging and MR spectroscopy at 1.5 T and immediately initiated cART. Imaging was repeated at 24 months. Regional brain volumes were quantified using FreeSurfer's longitudinal pipeline. Voxel-wise analyses using tensor-based morphometry (TBM) were conducted to verify regional assessments. Baseline brain metabolite levels, blood and cerebrospinal fluid biomarkers assessed by ELISA, and peripheral blood monocyte phenotypes measured by flow cytometry were examined as predictors of significant volumetric change., Results: Participants were 31 ± 8 years old. The estimated mean duration of infection at cART initiation was 15 days. Longitudinal analyses revealed reductions in volumes of putamen (P < 0.001) and caudate (P = 0.006). TBM confirmed significant atrophy in the putamen and caudate, and also in thalamic and hippocampal regions. In exploratory post-hoc analyses, higher baseline frequency of P-selectin glycoprotein ligand-1 (PSGL-1)-expressing total monocytes correlated with greater caudate volumetric decrease (ρ = 0.67, P = 0.017), whereas the baseline density of PSGL-1-expressing inflammatory (CD14CD16) monocytes correlated with putamen atrophy (ρ = 0.65, P = 0.022)., Conclusion: Suppressive cART initiated during AHI may not prevent brain atrophy. Volumetric decrease appears greater than expected age-related decline, although examination of longitudinal change in demographically similar HIV-uninfected Thai individuals is needed. Mechanisms underlying progressive HIV-related atrophy may include early activation and enhanced adhesive and migratory capacity of circulating monocyte populations.
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- 2020
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30. Distribution of Human Immunodeficiency Virus (HIV) Ribonucleic Acid in Cerebrospinal Fluid and Blood Is Linked to CD4/CD8 Ratio During Acute HIV.
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Chan P, Patel P, Hellmuth J, Colby DJ, Kroon E, Sacdalan C, Pinyakorn S, Jagodzinski L, Krebs S, Ananworanich J, Valcour V, and Spudich S
- Subjects
- Acute Disease, Adult, CD4-CD8 Ratio, Central Nervous System virology, Female, HIV pathogenicity, HIV Infections blood, HIV Infections cerebrospinal fluid, Humans, Male, Thailand, Virus Internalization, Young Adult, HIV genetics, HIV Infections immunology, RNA, Viral blood, RNA, Viral cerebrospinal fluid
- Abstract
Background: Human immunodeficiency virus (HIV) ribonucleic acid (RNA) levels in the plasma and cerebrospinal fluid (CSF) are correlated in chronic HIV infection, but their dynamics have not been characterized during acute infection., Methods: This study analyzed predictors of CSF HIV RNA and relative degree of CNS viral transmigration expressed as plasma minus CSF HIV log10 RNA (PCratio) during untreated acute HIV infection. Cerebrospinal fluid immune markers were compared between groups with different PCratio., Results: One hundred seventeen mostly male (97%) participants in the RV254 cohort in Bangkok, Thailand, had a median age of 28 years and an estimated median 18 days duration of infection; 43 (37%) were Fiebig stages I/II. Twenty-seven (23%) had CSF HIV RNA <80 copies/mL. Those with quantifiable levels (n = 90) had median CSF HIV RNA and PCratio of 3.76 and 2.36 log10 copies/mL, respectively. Human immunodeficiency virus RNA peaked at Fiebig III in plasma and Fiebig IV in CSF. In multivariable analyses, plasma HIV RNA and CD4/CD8 ratio independently correlated with CSF HIV RNA (P < .001), whereas CD4/CD8 ratio predicted PCratio (P = .018). Participants with PCratio <1 had higher CSF neopterin, soluble (s)CD163, interleukin-6, and sCD14 levels (all P < .05)., Conclusions: CD4/CD8 ratio independently correlated with CSF HIV RNA and PCratio, suggesting that immune responses modulate central nervous system viral entry at early infection.
- Published
- 2018
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31. Tracking Human Immunodeficiency Virus-1 Infection in the Humanized DRAG Mouse Model.
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Kim J, Peachman KK, Jobe O, Morrison EB, Allam A, Jagodzinski L, Casares SA, and Rao M
- Abstract
Humanized mice are emerging as an alternative model system to well-established non-human primate (NHP) models for studying human immunodeficiency virus (HIV)-1 biology and pathogenesis. Although both NHP and humanized mice have their own strengths and could never truly reflect the complex human immune system and biology, there are several advantages of using the humanized mice in terms of using primary HIV-1 for infection instead of simian immunodeficiency virus or chimera simian/HIV. Several different types of humanized mice have been developed with varying levels of reconstitution of human CD45
+ cells. In this study, we utilized humanized Rag1KO.IL2RγcKO.NOD mice expressing HLA class II (DR4) molecule (DRAG mice) infused with HLA-matched hematopoietic stem cells from umbilical cord blood to study early events after HIV-1 infection, since the mucosal tissues of these mice are highly enriched for human lymphocytes and express the receptors and coreceptors needed for HIV-1 entry. We examined the various tissues on days 4, 7, 14, and 21 after an intravaginal administration of a single dose of purified primary HIV-1. Plasma HIV-1 RNA was detected as early as day 7, with 100% of the animals becoming plasma RNA positive by day 21 post-infection. Single cells were isolated from lymph nodes, bone marrow, spleen, gut, female reproductive tissue, and brain and analyzed for gag RNA and strong stop DNA by quantitative (RT)-PCR. Our data demonstrated the presence of HIV-1 viral RNA and DNA in all of the tissues examined and that the virus was replication competent and spread rapidly. Bone marrow, gut, and lymph nodes were viral RNA positive by day 4 post-infection, while other tissues and plasma became positive typically between 7 and 14 days post-infection. Interestingly, the brain was the last tissue to become HIV-1 viral RNA and DNA positive by day 21 post-infection. These data support the notion that humanized DRAG mice could serve as an excellent model for studying the trafficking of HIV-1 to the various tissues, identification of cells harboring the virus, and thus could serve as a model system for HIV-1 pathogenesis and reservoir studies.- Published
- 2017
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32. High Number of Activated CD8+ T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection.
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Kessing CF, Spudich S, Valcour V, Cartwright P, Chalermchai T, Fletcher JL, Takata H, Nichols C, Josey BJ, Slike B, Krebs SJ, Sailsuta N, Lerdlum S, Jagodzinski L, Tipsuk S, Suttichom D, Rattanamanee S, Zetterberg H, Hellmuth J, Phanuphak N, Robb ML, Michael NL, Ananworanich J, and Trautmann L
- Subjects
- Humans, Immunophenotyping, CD8-Positive T-Lymphocytes immunology, Cerebrospinal Fluid cytology, Cerebrospinal Fluid immunology, HIV Antigens immunology, HIV Infections immunology, HIV Infections pathology, T-Lymphocyte Subsets immunology
- Abstract
Background: Central nervous system (CNS) infiltration by CD8 T cells is associated with neuroinflammation in many neurodegenerative diseases, including HIV-associated dementia. However, the role of CD8 T cells in the CNS during acute HIV infection (AHI) is unknown., Methods: We analyzed the phenotype, gene expression, T cell receptor (TCR) repertoire, and HIV specificity of CD8 T cells in cerebrospinal fluid (CSF) of a unique cohort captured during the earliest stages of AHI (n = 26), chronic (n = 23), and uninfected (n = 8)., Results: CSF CD8 T cells were elevated in AHI compared with uninfected controls. The frequency of activated CSF CD8 T cells positively correlated to CSF HIV RNA and to markers of CNS inflammation. In contrast, activated CSF CD8 T cells during chronic HIV infection were associated with markers of neurological injury and microglial activation. CSF CD8 T cells in AHI exhibited increased functional gene expression profiles associated with CD8 T cells effector function, proliferation, and TCR signaling, a unique restricted TCR Vbeta repertoire and contained HIV-specific CD8 T cells directed to unique HIV epitopes compared with the periphery., Conclusions: These results suggest that CSF CD8 T cells in AHI expanding in the CNS are functional and directed against HIV antigens. These cells could thus play a beneficial role protective of injury seen in chronic HIV infection if combination antiretroviral therapy is initiated early.
- Published
- 2017
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33. Sex differences in soluble markers vary before and after the initiation of antiretroviral therapy in chronically HIV-infected individuals.
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Krebs SJ, Slike BM, Sithinamsuwan P, Allen IE, Chalermchai T, Tipsuk S, Phanuphak N, Jagodzinski L, Kim JH, Ananworanich J, Marovich MA, and Valcour VG
- Subjects
- Adult, Cerebrospinal Fluid chemistry, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Plasma chemistry, Thailand, Young Adult, Anti-Retroviral Agents therapeutic use, HIV Infections drug therapy, HIV Infections pathology, Immunologic Factors blood, Immunologic Factors cerebrospinal fluid, Sex Factors
- Abstract
Objective: To evaluate differences in soluble inflammatory markers between chronically HIV-infected men and women, with or without cognitive impairment, and in response to treatment., Design: Soluble biomarkers were measured in cryopreserved plasma and cerebrospinal fluid (CSF) of 60 treatment-naïve individuals (25 men and 35 women) with chronic HIV infection and 18 HIV-uninfected controls (9 men and 9 women) from Thailand. Following enrollment, participants began combination antiretroviral therapy and were evaluated for expression of these markers after 48 weeks., Methods: Plasma and CSF levels of 19 soluble biomarkers (IFN-γ, TNFα, TNF-RII, IL-1α, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-15, MCP-1, t-Tau, IP-10, neopterin, IFNα, I-FABP, and sCD14) were measured using either a multiparameter or standard ELISA assay., Results: Prior to combination antiretroviral therapy, women with impaired cognition had elevated levels of neopterin and TNF-RII compared with women with normal cognition in both the plasma and CSF; however, levels did not differ between cognitively impaired or normal men. In a secondary outcome-hypothesis generating analysis, sex differences were also pronounced in plasma levels of MCP-1, IL-10, I-FABP, and sCD14 in response to treatment. Neopterin, IP-10, TNFα, TNF-RII, IFNα, MCP-1, IL-8, I-FABP, and sCD14 plasma levels remained elevated following 48 weeks of therapy in both sexes compared with uninfected controls., Conclusion: We provide evidence of sustained immune activation after 48 weeks of treatment and identify possible sex differences in biomarkers previously linked to cognitive impairment, chronic inflammation, and gut integrity that may contribute to immunological differences between sexes in relationship to disease progression and response to therapy.
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- 2016
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34. Expansion of Inefficient HIV-Specific CD8 T Cells during Acute Infection.
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Eller MA, Goonetilleke N, Tassaneetrithep B, Eller LA, Costanzo MC, Johnson S, Betts MR, Krebs SJ, Slike BM, Nitayaphan S, Rono K, Tovanabutra S, Maganga L, Kibuuka H, Jagodzinski L, Peel S, Rolland M, Marovich MA, Kim JH, Michael NL, Robb ML, and Streeck H
- Subjects
- Acute Disease, Adolescent, Adult, CD4-Positive T-Lymphocytes immunology, Cell Proliferation, Epitopes, Female, HIV Infections virology, Humans, Immunophenotyping, Lymphocyte Count, Male, Middle Aged, T-Lymphocyte Subsets immunology, Viral Load, Virus Replication, Young Adult, CD8-Positive T-Lymphocytes immunology, HIV Infections immunology
- Abstract
Unlabelled: Attrition within the CD4(+)T cell compartment, high viremia, and a cytokine storm characterize the early days after HIV infection. When the first emerging HIV-specific CD8(+)T cell responses gain control over viral replication it is incomplete, and clearance of HIV infection is not achieved even in the rare cases of individuals who spontaneously control viral replication to nearly immeasurably low levels. Thus, despite their partial ability to control viremia, HIV-specific CD8(+)T cell responses are insufficient to clear HIV infection. Studying individuals in the first few days of acute HIV infection, we detected the emergence of a unique population of CD38(+)CD27(-)CD8(+)T cells characterized by the low expression of the CD8 receptor (CD8(dim)). Interestingly, while high frequencies of HIV-specific CD8(+)T cell responses occur within the CD38(+)CD27(-)CD8(dim)T cell population, the minority populations of CD8(bright)T cells are significantly more effective in inhibiting HIV replication. Furthermore, the frequency of CD8(dim)T cells directly correlates with viral load and clinical predictors of more rapid disease progression. We found that a canonical burst of proliferative cytokines coincides with the emergence of CD8(dim)T cells, and the size of this population inversely correlates with the acute loss of CD4(+)T cells. These data indicate, for the first time, that early CD4(+)T cell loss coincides with the expansion of a functionally impaired HIV-specific CD8(dim)T cell population less efficient in controlling HIV viremia., Importance: A distinct population of activated CD8(+)T cells appears during acute HIV infection with diminished capacity to inhibit HIV replication and is predictive of viral set point, offering the first immunologic evidence of CD8(+)T cell dysfunction during acute infection., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)
- Published
- 2016
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35. Virological and immunological characteristics of HIV-infected individuals at the earliest stage of infection.
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Ananworanich J, Sacdalan CP, Pinyakorn S, Chomont N, de Souza M, Luekasemsuk T, Schuetz A, Krebs SJ, Dewar R, Jagodzinski L, Ubolyam S, Trichavaroj R, Tovanabutra S, Spudich S, Valcour V, Sereti I, Michael N, Robb M, Phanuphak P, Kim JH, and Phanuphak N
- Abstract
Background: The challenges of identifying acute HIV infection (AHI) have resulted in a lack of critical information on early AHI that constrains the development of therapeutics that are designed to eradicate HIV from the infected host., Methods: AHI participants were recruited from the Thai Red Cross Anonymous Clinic in Bangkok, Thailand into the RV254/SEARCH010 protocol and categorised according to Fiebig stages as follows: Fiebig I (HIV-RNA+, p24 Ag-, HIV IgM-) and Fiebig II-IV (HIV-RNA+, p24 Ag + or -, HIV IgM- or +, Western blot- or indeterminate). Proviral and viral burden and immune activation levels were compared between Fiebig stage groups at the time of AHI. CD4 and CD4/CD8 ratio were also compared between groups before and up to 96 weeks of ART., Results: Median age was 27 years and 96% were male. Fiebig I individuals had lower median HIV-DNA in mononuclear cells from blood (3 vs . 190 copies/10
6 cells) and gut (0 vs . 898 copies/106 cells), and lower HIV-RNA in blood (4.2 vs . 6.2 log10 copies/mL), gut (1.7 vs . 3.1 log10 copies/mg) and cerebrospinal fluid (2.0 vs . 3.8 log10 copies/mL), when compared to Fiebig II-IV individuals (all P <0.01). Median plasma sCD14 level was lower (1.1 vs . 1.6 μg/mL) in Fiebig I individuals as was the frequency of CD8+HLADR+CD38+ T cells in blood (7.6 vs . 14.9%, both P <0.05). The median plasma interleukin 6 levels were similar between stages (0.6 in Fiebig I vs . 0.5 pg/mL in Fiebig II-IV, P >0.05). The frequencies of CD4+HLA-DR+CD38+ T cells were also similar between these stages (2.1 vs . 2.6%, P >0.05). Median CD4 count and CD4/CD8 ratio were higher in Fiebig I: 508 vs . 340 cells/mm3 and 1.1 vs . 0.7, respectively (both P <0.001). After ART, CD4 cell count normalised by week 24 in Fiebig I and week 48 in Fiebig II-IV. However, CD4/CD8 ratio was lower in both groups after 96 weeks of ART compared to healthy Thais ( P =0.02)., Conclusions: Compared to later AHI stages, Fiebig I was associated with lower HIV burden in blood and tissue compartments, lower immune activation and higher CD4 and CD4/CD8 ratio. ART in Fiebig I-IV resulted in normalisation of CD4 cell count within the first year, supporting the benefit of early ART. However, the CD4/CD8 ratio was not normalised after 2 years of ART in all AHI stages, suggesting some degree of persistent immunological dysfunction even when ART was instituted as early as Fiebig I.- Published
- 2016
36. Neuropsychological Impairment in Acute HIV and the Effect of Immediate Antiretroviral Therapy.
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Kore I, Ananworanich J, Valcour V, Fletcher JL, Chalermchai T, Paul R, Reynolds J, Tipsuk S, Ubolyam S, Rattanamanee S, Jagodzinski L, Kim J, and Spudich S
- Subjects
- Adult, Antiretroviral Therapy, Highly Active, Female, HIV Infections drug therapy, Humans, Longitudinal Studies, Male, Neuropsychological Tests, Prospective Studies, Thailand, Treatment Outcome, Young Adult, Anti-Retroviral Agents therapeutic use, HIV Infections pathology, HIV Infections psychology, Nervous System Diseases drug therapy, Nervous System Diseases pathology, Psychomotor Disorders drug therapy, Psychomotor Disorders physiopathology
- Abstract
Objective: To investigate neuropsychological performance (NP) during acute HIV infection (AHI) before and after combination antiretroviral therapy (cART)., Design: Prospective study of Thai AHI participants examined at 3 and 6 months after initiation of cART., Methods: Thirty-six AHI participants were evaluated pre-cART at median 19 days since HIV exposure and 3 and 6 months after cART with the Grooved Pegboard test, Color Trails 1 & 2 (CT1, CT2), and Trail Making Test A. Raw scores were standardized to 251 age- and education-matched HIV-uninfected Thais. To account for learning effects, change in NP performance was compared with that of controls at 6 months. Analyses included multivariable regression, nonparametric repeated measures analysis of variance, and Mann-Whitney U test., Results: Baseline NP scores for the AHI group were within normal range (z-scores range: -0.26 to -0.13). NP performance improved on CT1, CT2, and Trail Making Test A in the initial 3 months (P < 0.01) with no significant change during the last 3 months. Only improvement in CT1 was greater than that seen in controls at 6 months (P = 0.018). Participants who performed >1 SD below normative means on ≥2 tests (n = 8) exhibited higher baseline cerebrospinal fluid HIV RNA (P = 0.047) and had no improvement after cART., Conclusions: Most AHI individuals had normal NP performance, and early cART slightly improved their psychomotor function. However, approximately 25% had impaired NP performance, which correlated with higher cerebrospinal fluid HIV RNA, and these abnormalities were not reversed by early cART possibly indicating limited reversibility of cognitive impairment in a subset of AHI individuals.
- Published
- 2015
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37. TFH cells accumulate in mucosal tissues of humanized-DRAG mice and are highly permissive to HIV-1.
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Allam A, Majji S, Peachman K, Jagodzinski L, Kim J, Ratto-Kim S, Wijayalath W, Merbah M, Kim JH, Michael NL, Alving CR, Casares S, and Rao M
- Subjects
- Animals, Antigens, Surface metabolism, B-Lymphocyte Subsets immunology, B-Lymphocyte Subsets metabolism, Disease Models, Animal, Disease Susceptibility, Female, Humans, Immunophenotyping, Inducible T-Cell Co-Stimulator Protein metabolism, Interleukins biosynthesis, Leukocyte Common Antigens metabolism, Lymphoid Tissue immunology, Lymphoid Tissue metabolism, Mice, Mice, Transgenic, Mucous Membrane metabolism, Peyer's Patches immunology, Peyer's Patches metabolism, Proto-Oncogene Proteins c-bcl-6 metabolism, Receptors, CCR5 metabolism, Receptors, CXCR3 metabolism, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, T-Lymphocyte Subsets virology, T-Lymphocytes, Helper-Inducer metabolism, HIV Infections immunology, HIV Infections virology, HIV-1 immunology, Mucous Membrane immunology, T-Lymphocytes, Helper-Inducer immunology, T-Lymphocytes, Helper-Inducer virology
- Abstract
CD4(+) T follicular helper cells (TFH) in germinal centers are required for maturation of B-cells. While the role of TFH-cells has been studied in blood and lymph nodes of HIV-1 infected individuals, its role in the mucosal tissues has not been investigated. We show that the gut and female reproductive tract (FRT) of humanized DRAG mice have a high level of human lymphocytes and a high frequency of TFH (CXCR5(+)PD-1(++)) and precursor-TFH (CXCR5(+)PD-1(+)) cells. The majority of TFH-cells expressed CCR5 and CXCR3 and are the most permissive to HIV-1 infection. A single low-dose intravaginal HIV-1 challenge of humanized DRAG mice results in 100% infectivity with accumulation of TFH-cells mainly in the Peyer's patches and FRT. The novel finding of TFH-cells in the FRT may contribute to the high susceptibility of DRAG mice to HIV-1 infection. This mouse model thus provides new opportunities to study TFH-cells and to evaluate HIV-1 vaccines.
- Published
- 2015
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38. Central nervous system viral invasion and inflammation during acute HIV infection.
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Valcour V, Chalermchai T, Sailasuta N, Marovich M, Lerdlum S, Suttichom D, Suwanwela NC, Jagodzinski L, Michael N, Spudich S, van Griensven F, de Souza M, Kim J, and Ananworanich J
- Subjects
- Acute Disease, Adult, Central Nervous System Infections cerebrospinal fluid, Central Nervous System Infections pathology, Female, HIV Infections cerebrospinal fluid, HIV Infections virology, Humans, Inflammation cerebrospinal fluid, Magnetic Resonance Imaging, Male, Middle Aged, RNA, Viral cerebrospinal fluid, Young Adult, Central Nervous System Infections virology, HIV Infections complications, Inflammation virology
- Abstract
Background: Understanding the earliest central nervous system (CNS) events during human immunodeficiency virus (HIV) infection is crucial to knowledge of neuropathogenesis, but these have not previously been described in humans., Methods: Twenty individuals who had acute HIV infection (Fiebig stages I-IV), with average 15 days after exposure, underwent clinical neurological, cerebrospinal fluid (CSF), magnetic resonance imaging, and magnetic resonance spectroscopy (MRS) characterization., Results: HIV RNA was detected in the CSF from 15 of 18 subjects as early as 8 days after estimated HIV transmission. Undetectable CSF levels of HIV (in 3 of 18) was noted during Fiebig stages I, II, and III, with plasma HIV RNA levels of 285651, 2321, and 81978 copies/mL, respectively. On average, the CSF HIV RNA level was 2.42 log(10) copies/mL lower than that in plasma. There were no cases in which the CSF HIV RNA level exceeded that in plasma. Headache was common during the acute retroviral syndrome (in 11 of 20 subjects), but no other neurological signs or symptoms were seen. Intrathecal immune activation was identified in some subjects with elevated CSF neopterin, monocyte chemotactic protein/CCL2, and interferon γ-induced protein 10/CXCL-10 levels. Brain inflammation was suggested by MRS., Conclusions: CSF HIV RNA was detectable in humans as early as 8 days after exposure. CNS inflammation was apparent by CSF analysis and MRS in some individuals during acute HIV infection.
- Published
- 2012
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39. Change in brain magnetic resonance spectroscopy after treatment during acute HIV infection.
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Sailasuta N, Ross W, Ananworanich J, Chalermchai T, DeGruttola V, Lerdlum S, Pothisri M, Busovaca E, Ratto-Kim S, Jagodzinski L, Spudich S, Michael N, Kim JH, and Valcour V
- Subjects
- Acute Disease, Adult, Anti-HIV Agents pharmacology, Brain pathology, Female, HIV Infections pathology, Humans, Magnetic Resonance Spectroscopy, Male, Middle Aged, Neurons drug effects, Neurons pathology, Quality Control, Treatment Outcome, Young Adult, Anti-HIV Agents therapeutic use, Brain drug effects, Brain metabolism, HIV Infections drug therapy, HIV Infections metabolism
- Abstract
Objective: Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART)., Methods: Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART., Results: After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months., Interpretation: We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury.
- Published
- 2012
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40. Secondary syphilis in cali, Colombia: new concepts in disease pathogenesis.
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Cruz AR, Pillay A, Zuluaga AV, Ramirez LG, Duque JE, Aristizabal GE, Fiel-Gan MD, Jaramillo R, Trujillo R, Valencia C, Jagodzinski L, Cox DL, Radolf JD, and Salazar JC
- Subjects
- Adolescent, Adult, Aged, Antibodies, Bacterial blood, Bacterial Proteins genetics, Bacterial Typing Techniques, Cluster Analysis, Cohort Studies, Colombia epidemiology, DNA Fingerprinting, DNA Polymerase I genetics, DNA, Bacterial genetics, DNA, Bacterial isolation & purification, Endemic Diseases, Female, Genotype, Humans, Male, Middle Aged, Molecular Epidemiology, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Reagins blood, Skin microbiology, Skin pathology, Syphilis, Cutaneous microbiology, Treponema pallidum classification, Treponema pallidum genetics, Young Adult, Syphilis, Cutaneous epidemiology, Syphilis, Cutaneous pathology, Treponema pallidum isolation & purification
- Abstract
Venereal syphilis is a multi-stage, sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum (Tp). Herein we describe a cohort of 57 patients (age 18-68 years) with secondary syphilis (SS) identified through a network of public sector primary health care providers in Cali, Colombia. To be eligible for participation, study subjects were required to have cutaneous lesions consistent with SS, a reactive Rapid Plasma Reagin test (RPR-titer > or = 1 : 4), and a confirmatory treponemal test (Fluorescent Treponemal Antibody Absorption test- FTA-ABS). Most subjects enrolled were women (64.9%), predominantly Afro-Colombian (38.6%) or mestizo (56.1%), and all were of low socio-economic status. Three (5.3%) subjects were newly diagnosed with HIV infection at study entry. The duration of signs and symptoms in most patients (53.6%) was less than 30 days; however, some patients reported being symptomatic for several months (range 5-240 days). The typical palmar and plantar exanthem of SS was the most common dermal manifestation (63%), followed by diffuse hypo- or hyperpigmented macules and papules on the trunk, abdomen and extremities. Three patients had patchy alopecia. Whole blood (WB) samples and punch biopsy material from a subset of SS patients were assayed for the presence of Tp DNA polymerase I gene (polA) target by real-time qualitative and quantitative PCR methods. Twelve (46%) of the 26 WB samples studied had quantifiable Tp DNA (ranging between 194.9 and 1954.2 Tp polA copies/ml blood) and seven (64%) were positive when WB DNA was extracted within 24 hours of collection. Tp DNA was also present in 8/12 (66%) skin biopsies available for testing. Strain typing analysis was attempted in all skin and WB samples with detectable Tp DNA. Using arp repeat size analysis and tpr RFLP patterns four different strain types were identified (14d, 16d, 13d and 22a). None of the WB samples had sufficient DNA for typing. The clinical and microbiologic observations presented herein, together with recent Cali syphilis seroprevalence data, provide additional evidence that venereal syphilis is highly endemic in this region of Colombia, thus underscoring the need for health care providers in the region to be acutely aware of the clinical manifestations of SS. This study also provides, for the first time, quantitative evidence that a significant proportion of untreated SS patients have substantial numbers of circulating spirochetes. How Tp is able to persist in the blood and skin of SS patients, despite the known presence of circulating treponemal opsonizing antibodies and the robust pro-inflammatory cellular immune responses characteristic of this stage of the disease, is not fully understood and requires further study.
- Published
- 2010
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41. HIV-1 MN Env 15-mer peptides better detect HIV-1 specific CD8 T cell responses compared with consensus subtypes B and M group 15-mer peptides.
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Rutebemberwa A, Currier JR, Jagodzinski L, McCutchan F, Birx D, Marovich M, and Cox JH
- Subjects
- Adult, CD4 Lymphocyte Count, Consensus Sequence genetics, Consensus Sequence immunology, Enzyme-Linked Immunosorbent Assay, Female, HIV Infections genetics, HIV-1 genetics, Humans, Immunity, Cellular genetics, Immunity, Cellular immunology, Male, Middle Aged, Viral Load, CD8-Positive T-Lymphocytes immunology, Gene Products, env metabolism, HIV Infections immunology, HIV-1 immunology, Interferon-gamma immunology
- Abstract
Objective: To compare the ability of three Env (15-mer) peptide sets derived from the HIV-1 MN, the subtype B consensus, and the group M consensus to detect HIV-1 specific interferon (IFN)-gamma responses in HIV-1 subtype B infected subjects., Methods: Peripheral blood mononuclear cells were obtained from 17 HIV-1 subtype B seropositive and 5 HIV-1 seronegative subjects. Peptide matrices comprising each peptide set were used in IFN-gamma Elispot assays to screen for T cell epitopes. Following matrix deconvolution, individual peptides were analyzed by IFN-gamma intracellular cytokine-staining to confirm and characterize the responding cells., Results: HIV specific IFN-gamma responses were detected in 17 of 17 HIV-1 seropositive and none of 5 HIV-1 seronegative subjects by Elispot. Within the 17 HIV-1 seropositives, 16, 14, and 11 subjects responded to MN, B consensus, and group M env peptides, respectively. Responses were confirmed by intracellular cytokine analysis in 14 subjects and were in the CD3CD8 compartment. Cross-recognition of 'equivalent' peptides (i.e., peptides mapping to the same sequence region from the three peptide sets) was observed in 9 of 17 subjects. Peptide set specific responses to individual peptides were also observed; 11, 1, and 1 subjects demonstrated peptide set specific responses to MN, B consensus, and consensus group M, respectively., Conclusion: MN derived Env peptides were better able to detect HIV-1 specific CD8 T cell responses, many of which were not detectable by the equivalent clade or group consensus peptides. No single peptide set detected all the IFN-gamma responses within an individual. These results demonstrate the importance of reagent selection for monitoring of HIV responses in HIV-1 infected individuals and subsequently vaccine recipients.
- Published
- 2005
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42. The AG recombinant IbNG and novel strains of group M HIV-1 are common in Cameroon.
- Author
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Carr JK, Torimiro JN, Wolfe ND, Eitel MN, Kim B, Sanders-Buell E, Jagodzinski LL, Gotte D, Burke DS, Birx DL, and McCutchan FE
- Subjects
- Acquired Immunodeficiency Syndrome epidemiology, Adult, Cameroon epidemiology, Female, Genetic Variation, HIV-1 classification, Humans, Male, Middle Aged, Molecular Sequence Data, Recombination, Genetic, Acquired Immunodeficiency Syndrome virology, Genome, Viral, HIV-1 genetics
- Abstract
The genetic diversity of group M HIV-1 is highest in west central Africa. Blood samples from four locations in Cameroon were collected to determine the molecular epidemiology of HIV-1. The C2-V5 region of envelope was sequenced from 39 of the 40 samples collected, and 7 samples were sequenced across the genome. All strains belonged to group M of HIV-1. The circulating recombinant form CRF02 AG (IbNG) was the most common strain (22/39, 56%). Two of these were confirmed by full genome analysis. Four samples (4/39, 10%) clustered with the sub-subtype F2 and one of these was confirmed by full genome sequencing. Recombinant forms, each different but containing subtype A, accounted for the next most common form (7/39, 18%). Among these recombinants, those combining subtypes A and G were the most common (4/7, 57%). Also found were 3 subtype A, 2 subtype G, and 1 subtype B strain. Many recombination break points were shared between IbNG and the other AG recombinants, though none of these other AG recombinants included IbNG as a parent. This suggests that there was an ancestral AG recombinant that gave rise to CRF02 AG (IbNG), the successful circulating recombinant form, and to others that were less successful and are now rare., (Copyright 2000 Academic Press.)
- Published
- 2001
- Full Text
- View/download PDF
43. Selective increases in HIV-specific neutralizing antibody and partial reconstitution of cellular immune responses during prolonged, successful drug therapy of HIV infection.
- Author
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Kim JH, Mascola JR, Ratto-Kim S, VanCott TC, Loomis-Price L, Cox JH, Michael NL, Jagodzinski L, Hawkes C, Mayers D, Gilliam BL, Birx DC, and Robb ML
- Subjects
- CD4 Lymphocyte Count, HIV Antibodies immunology, HIV Core Protein p24 immunology, HIV Infections drug therapy, HIV Infections virology, HIV-1 immunology, HIV-1 isolation & purification, Humans, Neutralization Tests, RNA, Viral blood, Viral Load, Anti-HIV Agents therapeutic use, Antiretroviral Therapy, Highly Active, HIV Antibodies biosynthesis, HIV Infections immunology, Immunity, Cellular
- Abstract
Because the immune response to HIV depends on viral gene expression, we examined the HIV-specific immune responses in persons whose viral load after highly active antiretroviral therapy (HAART) was <400 on at least 3 occasions over a 12-month interval. Eleven patients were identified. While there was little change in mean HIV-binding antibody (Ab) titers in this group, two persons mounted increases in HIV envelope-specific binding antibody. Neutralizing antibody (NAb) titers against a panel of HIV-1 primary isolates (BZ167, US1, and CM237) increased post-HAART (80% neutralization titer against US1, p = 0.06; against CM237, p = 0.04). The two persons with large increases in binding antibody also had increases in primary isolate NAb. Roughly half of HAART recipients had significant increases in neutralizing antibody to the primary isolates US1 and CM237. Compared with CD4-matched, non-HAART controls, there were significant increases in NAb against the subtype B primary isolate US1 (p < 0.0009); no increases were seen against more easily neutralized primary isolate BZ167. There were no differences after HAART in antibody-directed cellular cytotoxicity (ADCC). HAART resulted in a partial restoration of lymphoproliferative responses to recall antigens (tetanus and diphtheria). New responses developed to HIV Gag p24. No patient responded to HIV Env gp160 or gp120 either before or after HAART. The data underscore the lack of functional reconstitution of HIV-specific, CD4-mediated responses despite durable suppression of viral replication. In the setting of stable anti-HIV Ab levels, the development of increased NAb in certain individuals suggests that control of the virus by HAART may assist in immune control of HIV.
- Published
- 2001
- Full Text
- View/download PDF
44. Clinical implications of identifying non-B subtypes of human immunodeficiency virus type 1 infection.
- Author
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Walter EA, Gilliam B, Delmar JA, Spooner K, Morris JT, Aronson N, Wegner SA, Michael NL, and Jagodzinski LL
- Subjects
- Adult, Anti-HIV Agents therapeutic use, CD4 Lymphocyte Count, Follow-Up Studies, Genotype, HIV Infections blood, HIV Infections virology, Humans, Male, Military Personnel, RNA, Viral blood, RNA, Viral drug effects, Time Factors, Viral Load, HIV Infections diagnosis, HIV-1 classification, HIV-1 drug effects, HIV-1 genetics
- Abstract
Although human immunodeficiency virus type 1 (HIV-1) infection in the United States has predominantly involved subtype B, increasing global travel is leading to wider dissemination of genetically heterogeneous subtypes. While physicians depend on HIV-1 viral load measurements to guide antiretroviral therapy, commonly used molecular assays may underestimate the viral load of patients with non-B subtypes. Nine patients with non-B subtypes of HIV-1 were identified by physicians who suspected a non-B subtype on the basis of a low or undetectable HIV-1 viral load, by the Amplicor HIV-1 Monitor test, version 1.0, in conjunction with either a declining CD4 cell count or history of travel outside the United States. Use of version 1.5 of the Amplicor HIV-1 Monitor test detected a median HIV-1 viral load that was 2.0 log(10) RNA copies/mL higher than was determined with version 1.0. Clinical management was altered in all cases after diagnosis of a non-B-subtype infection. These cases demonstrate that it is critical for physicians to suspect and diagnose non-B subtypes of HIV-1 so that an assay with reliable subtype performance can be used to guide antiretroviral therapy.
- Published
- 2000
- Full Text
- View/download PDF
45. Evaluation of performance of the Gen-Probe human immunodeficiency virus type 1 viral load assay using primary subtype A, C, and D isolates from Kenya.
- Author
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Emery S, Bodrug S, Richardson BA, Giachetti C, Bott MA, Panteleeff D, Jagodzinski LL, Michael NL, Nduati R, Bwayo J, Kreiss JK, and Overbaugh J
- Subjects
- Adult, Evaluation Studies as Topic, Female, HIV Core Protein p24 blood, HIV-1 classification, HIV-1 genetics, HIV-1 isolation & purification, Humans, Infant, Newborn, Kenya, RNA, Viral blood, Reagent Kits, Diagnostic, Reproducibility of Results, HIV Infections virology, HIV-1 physiology, Nucleic Acid Probes, Viral Load
- Abstract
Accurate and sensitive quantification of human immunodeficiency virus type 1 (HIV-1) RNA has been invaluable as a marker for disease prognosis and for clinical monitoring of HIV-1 disease. The first generation of commercially available HIV-1 RNA tests were optimized to detect the predominant HIV-1 subtype found in North America and Europe, subtype B. However, these tests are frequently suboptimal in detecting HIV-1 genetic forms or subtypes found in other parts of the world. The goal of the present study was to evaluate the performance of a new viral load assay with non-subtype B viruses. A transcription-mediated amplification method for detection and quantitation of diverse HIV-1 subtypes, called the Gen-Probe HIV-1 viral load assay, is under development. In this study we examined the performance of the Gen-Probe HIV-1 viral load assay relative to that of the commonly used commercial HIV-1 RNA assays using a panel of primary isolates from Kenya. For comparison, we included several subtype B cloned viruses, and we quantified each virus using an in-house quantitative-competitive reverse transcriptase PCR (QC-RT-PCR) method and gag(p24) antigen capture. The Gen-Probe HIV-1 viral load assay and a version of the Roche AMPLICOR HIV-1 MONITOR test (version 1.5) that was designed to detect a broader range of subtypes were both sensitive for the quantification of Kenyan primary isolates, which represented subtype A, C, and D viruses. The Gen-Probe HIV-1 viral load assay was more sensitive for the majority of viruses than the Roche AMPLICOR HIV-1 MONITOR test version 1.0, the Bayer Quantiplex HIV RNA 3.0 assay, or a QC-RT-PCR method in use in our laboratory, suggesting that it provides a useful method for quantifying HIV-1 RNAs from diverse parts of the world, including Africa.
- Published
- 2000
- Full Text
- View/download PDF
46. Use of calibrated viral load standards for group M subtypes of human immunodeficiency virus type 1 to assess the performance of viral RNA quantitation tests.
- Author
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Jagodzinski LL, Wiggins DL, McManis JL, Emery S, Overbaugh J, Robb M, Bodrug S, and Michael NL
- Subjects
- Acquired Immunodeficiency Syndrome blood, Calibration, Geography, HIV-1 isolation & purification, Humans, Reproducibility of Results, Acquired Immunodeficiency Syndrome diagnosis, HIV-1 classification, RNA, Viral blood, Viral Load methods
- Abstract
Optimal management of human immunodeficiency virus type 1 (HIV-1) disease requires accurate quantitation of viral RNA concentrations in plasma. Evidence for increasing geographic intermixing of HIV-1 subtypes makes equivalent quantitation of all subtypes essential. The performances of six quantitative viral RNA tests are described, for the first time, with calibrated viral isolates of diverse subtypes.
- Published
- 2000
- Full Text
- View/download PDF
47. Development of calibrated viral load standards for group M subtypes of human immunodeficiency virus type 1 and performance of an improved AMPLICOR HIV-1 MONITOR test with isolates of diverse subtypes.
- Author
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Michael NL, Herman SA, Kwok S, Dreyer K, Wang J, Christopherson C, Spadoro JP, Young KK, Polonis V, McCutchan FE, Carr J, Mascola JR, Jagodzinski LL, and Robb ML
- Subjects
- Acquired Immunodeficiency Syndrome blood, Biological Assay methods, Biological Assay standards, HIV-1 genetics, Humans, RNA, Viral analysis, Reference Standards, Reverse Transcriptase Polymerase Chain Reaction, Acquired Immunodeficiency Syndrome virology, HIV-1 isolation & purification, Viral Load
- Abstract
Accurate determination of plasma human immunodeficiency virus type 1 (HIV-1) RNA levels is critical for the effective management of HIV-1 disease. The AMPLICOR HIV-1 MONITOR Test, a reverse transcription-PCR-based test for quantification of HIV-1 RNA in plasma, was developed when little sequence information on HIV-1 isolates from outside North America was available. It has since become apparent that many non-subtype B isolates, particularly subtypes A and E, are detected inefficiently by the test. We describe here the AMPLICOR HIV-1 MONITOR Test, version 1.5, an upgraded test developed to minimize subtype-related variation. We also developed a panel of HIV-1 standards containing 30 HIV-1 isolates of subtypes A through G. The virus particle concentration of each cultured viral stock was standardized by electron microscopic virus particle counting. We used this panel to determine the performance of the original AMPLICOR HIV-1 MONITOR Test and version 1.5 of the test with HIV-1 subtypes A through G. The original test underestimated the concentration of HIV-1 subtype A, E, F, and G RNA by 10-fold or more, whereas version of the 1.5 test yielded equivalent quantification of HIV-1 RNA regardless of the subtype. In light of the increasing intermixing of HIV-1 subtypes worldwide, standardization of PCR-based tests against well-characterized viral isolates representing the full range of HIV-1 diversity will be essential for the continued utility of these important clinical management tools.
- Published
- 1999
- Full Text
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48. Serum levels of virus burden in early-stage human immunodeficiency virus type 1 disease in women.
- Author
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Evans JS, Nims T, Cooley J, Bradley W, Jagodzinski L, Zhou S, Melcher GP, Burke DS, and Vahey M
- Subjects
- Adult, DNA, Viral blood, Female, Humans, Male, Sex Factors, Acquired Immunodeficiency Syndrome virology, HIV-1 isolation & purification, Viremia virology
- Abstract
The fundamental clinical, viral, and immunologic features of early-stage human immunodeficiency virus type 1 (HIV-1) disease were examined in a seroprevalent cohort of 28 men and 14 women assessed longitudinally at three equally dispersed time points over a mean of 43 months. There were no gender differences in the relative risk of developing AIDS-defining end points or death. The median serum RNA levels assessed at the three study time points were 3.3-, 4.9-, and 1.5-fold lower, respectively, in women than in men. This suggests that while serum virus load may be as powerful a correlate of disease status in women as it is in men, the absolute values of the virus levels may be different in the 2 populations. These observations may have implications for the interpretation of levels of virus burden in women for the assessment of disease progression, transmission, and treatment.
- Published
- 1997
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49. Antiviral effect and ex vivo CD4+ T cell proliferation in HIV-positive patients as a result of CD28 costimulation.
- Author
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Levine BL, Mosca JD, Riley JL, Carroll RG, Vahey MT, Jagodzinski LL, Wagner KF, Mayers DL, Burke DS, Weislow OS, St Louis DC, and June CH
- Subjects
- Antibodies, Monoclonal immunology, CD3 Complex immunology, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes cytology, Cell Division, Cells, Cultured, Chemokines metabolism, Cytokines metabolism, HIV Infections immunology, HIV-1 immunology, Humans, Interleukin-2 pharmacology, Phytohemagglutinins pharmacology, Virus Integration, Virus Replication, CD28 Antigens immunology, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes virology, HIV Infections virology, HIV-1 physiology, Lymphocyte Activation
- Abstract
Because stimulation of CD4+ lymphocytes leads to activation of human immunodeficiency virus-type 1 (HIV-1) replication, viral spread, and cell death, adoptive CD4+ T cell therapy has not been possible. When antigen and CD28 receptors on cultured T cells were stimulated by monoclonal antibodies (mAbs) to CD3 and CD28 that had been immobilized, there was an increase in the number of polyclonal CD4+ T cells from HIV-infected donors. Activated cells predominantly secreted cytokines associated with T helper cell type 1 function. The HIV-1 viral load declined in the absence of antiretroviral agents. Moreover, CD28 stimulation of CD4+ T cells from uninfected donors rendered these cells highly resistant to HIV-1 infection. Immobilization of CD28 mAb was crucial to the development of HIV resistance, as cells stimulated with soluble CD28 mAb were highly susceptible to HIV infection. The CD28-mediated antiviral effect occurred early in the viral life cycle, before HIV-1 DNA integration. These data may facilitate immune reconstitution and gene therapy approaches in persons with HIV infection.
- Published
- 1996
- Full Text
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50. New human and simian HIV-related retroviruses possess functional transactivator (tat) gene.
- Author
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Arya SK, Beaver B, Jagodzinski L, Ensoli B, Kanki PJ, Albert J, Fenyo EM, Biberfeld G, Zagury JF, and Laure F
- Subjects
- Animals, Base Sequence, Cell Transformation, Viral, Cloning, Molecular, Gene Expression Regulation, Humans, Acquired Immunodeficiency Syndrome veterinary, Cercopithecus microbiology, Chlorocebus aethiops microbiology, Deltaretrovirus genetics, Genes, Regulator, Genes, Viral, HIV genetics, Monkey Diseases microbiology, Retroviridae genetics
- Abstract
New human retroviruses antigenically related to HIV and even more closely to STLV-III have been recently isolated from individuals from some West African countries. One of these viruses, HTLV-IVP, was reportedly isolated from lymphocytes of a healthy female prostitute. Another isolate, LAV-2FG, was obtained from an AIDS patient and third, SBL-6669, from an individual with lymphadenopathy. Current epidemiological studies indicate that some of these virus isolates cause immune deficiency whereas others may not or may be less efficient at inducing immune deficiency. Similarly, STLV-III apparently does not cause immune deficiency in its natural host, African green monkey. A novel feature of HIV is the possession of a gene termed tat, which is implicated in its pathobiology. We report here that, like HIV, HTLV-IVP, LAV-2FG (HIV-2) and SBL-6669, as well as STLV-IIIAGM possess the putative tat gene, irrespective of their pathogenic potential in vivo. Interestingly, HTLV-IVP/LAV-2FG long terminal repeat (LTR) is equally well transactivated by the HTLV-IVP/LAV-2FG and HTLV-IIIB tat function, HTLV-IIIB LTR responds better to its own tat function.
- Published
- 1987
- Full Text
- View/download PDF
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