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  1. Article ; Online: Substance abuse, HIV-1 and hepatitis.

    Parikh, Nirzari / Nonnemacher, Michael R / Pirrone, Vanessa / Block, Timothy / Mehta, Anand / Wigdahl, Brian

    Current HIV research

    2012  Volume 10, Issue 7, Page(s) 557–571

    Abstract: During the course of human immunodeficiency virus type 1 (HIV-1) disease, the virus has been shown to effectively escape the immune response with the subsequent establishment of latent viral reservoirs in specific cell populations within the peripheral ... ...

    Abstract During the course of human immunodeficiency virus type 1 (HIV-1) disease, the virus has been shown to effectively escape the immune response with the subsequent establishment of latent viral reservoirs in specific cell populations within the peripheral blood (PB) and associated lymphoid tissues, bone marrow (BM), brain, and potentially other end organs. HIV-1, along with hepatitis B and C viruses (HBV and HCV), are known to share similar routes of transmission, including intravenous drug use, blood transfusions, sexual intercourse, and perinatal exposure. Substance abuse, including the use of opioids and cocaine, is a significant risk factor for exposure to HIV-1 and the development of acquired immune deficiency syndrome, as well as HBV and HCV exposure, infection, and disease. Thus, coinfection with HIV-1 and HBV or HCV is common and may be impacted by chronic substance abuse during the course of disease. HIV- 1 impacts the natural course of HBV and HCV infection by accelerating the progression of HBV/HCV-associated liver disease toward end-stage cirrhosis and quantitative depletion of the CD4+ T-cell compartment. HBV or HCV coinfection with HIV-1 is also associated with increased mortality when compared to either infection alone. This review focuses on the impact of substance abuse and coinfection with HBV and HCV in the PB, BM, and brain on the HIV-1 pathogenic process as it relates to viral pathogenesis, disease progression, and the associated immune response during the course of this complex interplay. The impact of HIV-1 and substance abuse on hepatitis virus-induced disease is also a focal point.
    MeSH term(s) Acquired Immunodeficiency Syndrome/epidemiology ; Acquired Immunodeficiency Syndrome/immunology ; Acquired Immunodeficiency Syndrome/mortality ; Acquired Immunodeficiency Syndrome/transmission ; Blood/immunology ; Blood/virology ; Bone Marrow/immunology ; Bone Marrow/virology ; Brain/immunology ; Brain/virology ; Coinfection ; Disease Progression ; Female ; HIV Seropositivity/epidemiology ; HIV Seropositivity/immunology ; HIV Seropositivity/mortality ; HIV Seropositivity/transmission ; HIV-1/immunology ; Hepatitis B/epidemiology ; Hepatitis B/immunology ; Hepatitis B/mortality ; Hepatitis B/transmission ; Hepatitis C/epidemiology ; Hepatitis C/immunology ; Hepatitis C/mortality ; Hepatitis C/transmission ; Humans ; Male ; Substance Abuse, Intravenous/epidemiology ; Substance Abuse, Intravenous/immunology ; Substance Abuse, Intravenous/mortality ; United States/epidemiology
    Language English
    Publishing date 2012-09-13
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2192348-6
    ISSN 1873-4251 ; 1570-162X
    ISSN (online) 1873-4251
    ISSN 1570-162X
    DOI 10.2174/157016212803306023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Cocaine alters cytokine profiles in HIV-1-infected African American individuals in the DrexelMed HIV/AIDS genetic analysis cohort.

    Parikh, Nirzari / Dampier, Will / Feng, Rui / Passic, Shendra R / Zhong, Wen / Frantz, Brian / Blakey, Brandon / Aiamkitsumrit, Benjamas / Pirrone, Vanessa / Nonnemacher, Michael R / Jacobson, Jeffrey M / Wigdahl, Brian

    Journal of acquired immune deficiency syndromes (1999)

    2014  Volume 66, Issue 3, Page(s) 256–264

    Abstract: Background: This study evaluated the relationship between illicit drug use and HIV-1 disease severity in HIV-1-infected patients enrolled in the DREXELMED HIV/AIDS Genetic Analysis Cohort. Because cocaine is known to have immunomodulatory effects, the ... ...

    Abstract Background: This study evaluated the relationship between illicit drug use and HIV-1 disease severity in HIV-1-infected patients enrolled in the DREXELMED HIV/AIDS Genetic Analysis Cohort. Because cocaine is known to have immunomodulatory effects, the cytokine profiles of preferential nonusers, cocaine users, and multidrug users were analyzed to understand the effects of cocaine on cytokine modulation and HIV-1 disease severity.
    Methods: Patients within the cohort were assessed approximately every 6 months for HIV-1 clinical markers and for history of illicit drug, alcohol, and tobacco use. The Luminex human cytokine 30-plex panel was used for cytokine quantitation. Analysis was performed using a newly developed biostatistical model.
    Results: Substance abuse was common within the cohort. Using the drug screens at the time of each visit, the subjects in the cohort were categorized as preferential nonusers, cocaine users, or multidrug users. The overall health of the nonuser population was better than that of the cocaine users, with peak and current viral loads in nonusers substantially lower than those in cocaine and multidrug users. Among the 30 cytokines investigated, differential levels were established within the 3 populations. The T-helper 2 cytokines, interleukin-4 and -10, known to play a critical role during HIV-1 infection, were positively associated with increasing cocaine use. Clinical parameters such as latest viral load, CD4 T-cell counts, and CD4:CD8 ratio were also significantly associated with cocaine use, depending on the statistical model used.
    Conclusions: Based on these assessments, cocaine use seems to be associated with more severe HIV-1 disease.
    MeSH term(s) Adult ; African Americans ; Cocaine-Related Disorders/immunology ; Cocaine-Related Disorders/virology ; Cohort Studies ; Cytokines/metabolism ; Female ; HIV Infections/immunology ; HIV Infections/virology ; HIV-1 ; Humans ; Male ; Middle Aged ; Severity of Illness Index ; Viral Load
    Chemical Substances Cytokines
    Language English
    Publishing date 2014-04-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 645053-2
    ISSN 1944-7884 ; 1077-9450 ; 0897-5965 ; 0894-9255 ; 1525-4135
    ISSN (online) 1944-7884 ; 1077-9450
    ISSN 0897-5965 ; 0894-9255 ; 1525-4135
    DOI 10.1097/QAI.0000000000000163
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2442: Show issues Location:
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  3. Article: The prevalence of, and molecular defects underlying, inherited protein S deficiency in the general population.

    Beauchamp, Nicholas J / Dykes, Anne C / Parikh, Nirzari / Campbell Tait, R / Daly, Martina E

    British journal of haematology

    2004  Volume 125, Issue 5, Page(s) 647–654

    Abstract: The molecular basis of protein S (PS) deficiency was investigated in seven of eight donors identified with persistently low plasma PS levels from a survey of PS levels in 3788 Scottish blood donors. PROS1 gene analysis identified at least one defect in ... ...

    Abstract The molecular basis of protein S (PS) deficiency was investigated in seven of eight donors identified with persistently low plasma PS levels from a survey of PS levels in 3788 Scottish blood donors. PROS1 gene analysis identified at least one defect in six donors. Five were heterozygous for the Heerlen polymorphism predicting a Ser460Pro substitution. Haplotype analysis revealed the possibility that this allele was inherited with the same haplotype in four of the five donors, suggesting a founder effect for the Heerlen allele in this population. One Heerlen allele carrier was also heterozygous for a 3 bp deletion 68-72 bp upstream of exon 2. Platelet PROS1 transcript analysis showed no reduction in mRNA expression from the affected allele in this donor. A T to G transversion 3 bp upstream of exon 12 was identified in one donor, which is predicted to reduce the efficiency of PS mRNA splicing. However, PROS1 transcript analysis showed no evidence of exon skipping or cryptic splicing. No PROS1 gene defect was detected in the remaining donor. This genetic information enabled us to refine our estimate of the prevalence of heritable PS deficiency in the Scottish population to between 0.16% and 0.21%, predominantly resulting from the presence of the Heerlen allele.
    MeSH term(s) Female ; Follow-Up Studies ; Gene Expression ; Gene Frequency ; Genes ; Heterozygote ; Humans ; Male ; Mutation/genetics ; Pedigree ; Prevalence ; Protein S/analysis ; Protein S Deficiency/blood ; Protein S Deficiency/epidemiology ; Protein S Deficiency/genetics ; Scotland/epidemiology
    Chemical Substances Protein S
    Language English
    Publishing date 2004-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/j.1365-2141.2004.04961.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Defining differential genetic signatures in CXCR4- and the CCR5-utilizing HIV-1 co-linear sequences.

    Aiamkitsumrit, Benjamas / Dampier, Will / Martin-Garcia, Julio / Nonnemacher, Michael R / Pirrone, Vanessa / Ivanova, Tatyana / Zhong, Wen / Kilareski, Evelyn / Aldigun, Hazeez / Frantz, Brian / Rimbey, Matthew / Wojno, Adam / Passic, Shendra / Williams, Jean W / Shah, Sonia / Blakey, Brandon / Parikh, Nirzari / Jacobson, Jeffrey M / Moldover, Brian /
    Wigdahl, Brian

    PloS one

    2014  Volume 9, Issue 9, Page(s) e107389

    Abstract: The adaptation of human immunodeficiency virus type-1 (HIV-1) to an array of physiologic niches is advantaged by the plasticity of the viral genome, encoded proteins, and promoter. CXCR4-utilizing (X4) viruses preferentially, but not universally, infect ... ...

    Abstract The adaptation of human immunodeficiency virus type-1 (HIV-1) to an array of physiologic niches is advantaged by the plasticity of the viral genome, encoded proteins, and promoter. CXCR4-utilizing (X4) viruses preferentially, but not universally, infect CD4+ T cells, generating high levels of virus within activated HIV-1-infected T cells that can be detected in regional lymph nodes and peripheral blood. By comparison, the CCR5-utilizing (R5) viruses have a greater preference for cells of the monocyte-macrophage lineage; however, while R5 viruses also display a propensity to enter and replicate in T cells, they infect a smaller percentage of CD4+ T cells in comparison to X4 viruses. Additionally, R5 viruses have been associated with viral transmission and CNS disease and are also more prevalent during HIV-1 disease. Specific adaptive changes associated with X4 and R5 viruses were identified in co-linear viral sequences beyond the Env-V3. The in silico position-specific scoring matrix (PSSM) algorithm was used to define distinct groups of X4 and R5 sequences based solely on sequences in Env-V3. Bioinformatic tools were used to identify genetic signatures involving specific protein domains or long terminal repeat (LTR) transcription factor sites within co-linear viral protein R (Vpr), trans-activator of transcription (Tat), or LTR sequences that were preferentially associated with X4 or R5 Env-V3 sequences. A number of differential amino acid and nucleotide changes were identified across the co-linear Vpr, Tat, and LTR sequences, suggesting the presence of specific genetic signatures that preferentially associate with X4 or R5 viruses. Investigation of the genetic relatedness between X4 and R5 viruses utilizing phylogenetic analyses of complete sequences could not be used to definitively and uniquely identify groups of R5 or X4 sequences; in contrast, differences in the genetic diversities between X4 and R5 were readily identified within these co-linear sequences in HIV-1-infected patients.
    MeSH term(s) Algorithms ; Cell Line ; Genes, Viral ; HIV-1/genetics ; HIV-1/metabolism ; Humans ; Receptors, CCR5/metabolism ; Receptors, CXCR4/metabolism
    Chemical Substances CCR5 protein, human ; CXCR4 protein, human ; Receptors, CCR5 ; Receptors, CXCR4
    Language English
    Publishing date 2014-09-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0107389
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Development of co-selected single nucleotide polymorphisms in the viral promoter precedes the onset of human immunodeficiency virus type 1-associated neurocognitive impairment.

    Li, Luna / Aiamkitsumrit, Benjamas / Pirrone, Vanessa / Nonnemacher, Michael R / Wojno, Adam / Passic, Shendra / Flaig, Katherine / Kilareski, Evelyn / Blakey, Brandon / Ku, Jade / Parikh, Nirzari / Shah, Rushabh / Martin-Garcia, Julio / Moldover, Brian / Servance, Laila / Downie, David / Lewis, Sharon / Jacobson, Jeffrey M / Kolson, Dennis /
    Wigdahl, Brian

    Journal of neurovirology

    2011  Volume 17, Issue 1, Page(s) 92–109

    Abstract: The long terminal repeat (LTR) regulates gene expression of HIV-1 by interacting with multiple host and viral factors. Cross-sectional studies in the pre-HAART era demonstrated that single nucleotide polymorphisms (SNPs) in peripheral blood-derived LTRs ( ...

    Abstract The long terminal repeat (LTR) regulates gene expression of HIV-1 by interacting with multiple host and viral factors. Cross-sectional studies in the pre-HAART era demonstrated that single nucleotide polymorphisms (SNPs) in peripheral blood-derived LTRs (a C-to-T change at position 3 of C/EBP site I (3T) and at position 5 of Sp site III (5T)) increased in frequency as disease severity increased. Additionally, the 3T variant correlated with HIV-1-associated dementia. LTR sequences derived by longitudinal sampling of peripheral blood from a single patient in the DrexelMed HIV/AIDS Genetic Analysis Cohort resulted in the detection of the 3T and 5T co-selected SNPs before the onset of neurologic impairment, demonstrating that these SNPs may be useful in predicting HIV-associated neurological complications. The relative fitness of the LTRs containing the 3T and/or 5T co-selected SNPs as they evolve in their native patient-derived LTR backbone structure demonstrated a spectrum of basal and Tat-mediated transcriptional activities using the IIIB-derived Tat and colinear Tat derived from the same molecular clone containing the 3T/5T LTR SNP. In silico predictions utilizing colinear envelope sequence suggested that the patient's virus evolved from an X4 to an R5 swarm prior to the development of neurological complications and more advanced HIV disease. These results suggest that the HIV-1 genomic swarm may evolve during the course of disease in response to selective pressures that lead to changes in prevalence of specific polymorphisms in the LTR, env, and/or tat that could predict the onset of neurological disease and result in alterations in viral function.
    MeSH term(s) AIDS Dementia Complex/virology ; Adult ; Amino Acid Sequence ; Base Sequence ; Cell Line ; Gene Expression Regulation, Viral ; Genotype ; HIV Infections/virology ; HIV Long Terminal Repeat ; HIV-1/genetics ; HIV-1/pathogenicity ; HIV-1/physiology ; Humans ; Longitudinal Studies ; Middle Aged ; Molecular Sequence Data ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Transcriptional Activation ; Virus Replication ; env Gene Products, Human Immunodeficiency Virus/genetics ; env Gene Products, Human Immunodeficiency Virus/metabolism ; tat Gene Products, Human Immunodeficiency Virus/genetics ; tat Gene Products, Human Immunodeficiency Virus/metabolism
    Chemical Substances env Gene Products, Human Immunodeficiency Virus ; tat Gene Products, Human Immunodeficiency Virus
    Language English
    Publishing date 2011-01-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1283265-0
    ISSN 1538-2443 ; 1355-0284
    ISSN (online) 1538-2443
    ISSN 1355-0284
    DOI 10.1007/s13365-010-0014-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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