RESUMO
BACKGROUND: Whether unique human immunodeficiency type 1 (HIV) genotypes occur in the genital tract is important for vaccine development and management of drug resistant viruses. Multiple cross-sectional studies suggest HIV is compartmentalized within the female genital tract. We hypothesize that bursts of HIV replication and/or proliferation of infected cells captured in cross-sectional analyses drive compartmentalization but over time genital-specific viral lineages do not form; rather viruses mix between genital tract and blood. METHODS: Eight women with ongoing HIV replication were studied during a period of 1.5 to 4.5 years. Multiple viral sequences were derived by single-genome amplification of the HIV C2-V5 region of env from genital secretions and blood plasma. Maximum likelihood phylogenies were evaluated for compartmentalization using 4 statistical tests. RESULTS: In cross-sectional analyses compartmentalization of genital from blood viruses was detected in three of eight women by all tests; this was associated with tissue specific clades containing multiple monotypic sequences. In longitudinal analysis, the tissues-specific clades did not persist to form viral lineages. Rather, across women, HIV lineages were comprised of both genital tract and blood sequences. CONCLUSIONS: The observation of genital-specific HIV clades only in cross-sectional analysis and an absence of genital-specific lineages in longitudinal analyses suggest a dynamic interchange of HIV variants between the female genital tract and blood.
Assuntos
Genitália Feminina/virologia , Infecções por HIV/sangue , HIV-1/patogenicidade , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética , Estudos Transversais , Feminino , Genes Virais , Genótipo , Glicosilação , Infecções por HIV/patologia , Infecções por HIV/virologia , HIV-1/genética , HIV-1/fisiologia , Humanos , Funções Verossimilhança , Estudos Longitudinais , Filogenia , RNA Viral/análise , RNA Viral/genética , Infecções do Sistema Genital/sangue , Infecções do Sistema Genital/patologia , Infecções do Sistema Genital/virologia , Análise de Sequência de RNA , Especificidade da Espécie , Fatores de Tempo , Replicação Viral , Produtos do Gene env do Vírus da Imunodeficiência Humana/sangue , Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismoRESUMO
This study evaluated the prediction that coping motives for marijuana use would mediate the relation between anxiety sensitivity and a marijuana dependence diagnosis after controlling for other co-occurring marijuana use motives. Participants were 136 current marijuana users (47.1% women; M(age)= 21.9, SD = 7.2). Results were consistent with a mediational effect, with the relation between anxiety sensitivity and marijuana dependence being explained by the addition of coping motives into the model. These results provide novel information related to the putative explanatory role of coping motives for marijuana use in the relation between anxiety sensitivity and marijuana dependence.
Assuntos
Adaptação Psicológica , Ansiedade/psicologia , Abuso de Maconha/psicologia , Fumar Maconha/psicologia , Ansiedade/complicações , Feminino , Humanos , Masculino , Abuso de Maconha/complicações , Modelos Psicológicos , Adulto JovemRESUMO
We present a novel gamma-chain dysfibrinogen that was discovered in a 32-year-old asymptomatic man admitted to the hospital after a car accident. He presented with a low fibrinogen concentration, 0.5 mg/mL, and a prolonged thrombin clotting time, 58 seconds. Analysis of purified fibrinogen by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a gamma-chain variant with an apparently higher molecular weight. Isoelectric focusing (IEF) demonstrated an anodal shift in the banding pattern of the chains and electrospray ionization mass spectrometry (ESIMS) showed a 27-Da increase in the average mass of the unresolved variant and normal gamma chains. DNA sequence analysis showed a heterozygous mutation of GGC (Gly)-->GAC (Asp) at codon 309 of the gamma chain gene. This Gly--> Asp substitution was consistent with the charge change shown by IEF as well as the mass change identified by ESIMS. Functional analysis revealed that thrombin-catalyzed polymerization occurred with a longer lag time, lower rate of lateral aggregation, and similar final turbidity compared to normal and that factor XIII cross-linking was normal. The polymerization results suggest that residue gamma309 is necessary for proper alignment of fibrinogen molecules, specifically in protofibril formation and D:D interactions. gammaGly309 is highly conserved and x-ray structures support the conclusion that the lack of a side chain at this position helps facilitate the close contact between abutting gammaD domains of condensing fibrin monomers during polymerization.
