1,721,014 research outputs found
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Impact of HIV on CD8+ T Cell CD57 Expression Is Distinct from That of CMV and Aging
Get PDFBackground: Chronic antigenic stimulation by cytomegalovirus (CMV) is thought to increase “immunosenesence” of aging, characterized by accumulation of terminally differentiated CD28- CD8+ T cells and increased CD57, a marker of proliferative history. Whether chronic HIV infection causes similar effects is currently unclear. Methods: We compared markers of CD8+ T cell differentiation (e.g., CD28, CD27, CCR7, CD45RA) and CD57 expression on CD28- CD8+ T cells in healthy HIV-uninfected adults with and without CMV infection and in both untreated and antiretroviral therapy (ART)-suppressed HIV-infected adults with asymptomatic CMV infection. Results: Compared to HIV-uninfected adults without CMV (n = 12), those with asymptomatic CMV infection (n = 31) had a higher proportion of CD28-CD8+ T cells expressing CD57 (P = 0.005). Older age was also associated with greater proportions of CD28-CD8+ T cells expressing CD57 (rho: 0.47, P = 0.007). In contrast, untreated HIV-infected CMV+ participants (n = 55) had much lower proportions of CD28- CD8+ cells expressing CD57 than HIV-uninfected CMV+ participants (P<0.0001) and were enriched for less well-differentiated CD28- transitional memory (TTR) CD8+ T cells (P<0.0001). Chronically HIV-infected adults maintaining ART-mediated viral suppression (n = 96) had higher proportions of CD28-CD8+ T cells expressing CD57 than untreated patients (P<0.0001), but continued to have significantly lower levels than HIV-uninfected controls (P = 0.001). Among 45 HIV-infected individuals initiating their first ART regimen, the proportion of CD28-CD8+ T cells expressing CD57 declined (P<0.0001), which correlated with a decline in percent of transitional memory CD8+ T cells, and appeared to be largely explained by a decline in CD28-CD57- CD8+ T cell counts rather than an expansion of CD28-CD57+ CD8+ T cell counts. Conclusions: Unlike CMV and aging, which are associated with terminal differentiation and proliferation of effector memory CD8+ T cells, HIV inhibits this process, expanding less well-differentiated CD28- CD8+ T cells and decreasing the proportion of CD28- CD8+ T cells that express CD57.Version of Recor
Human immunodeficiency virus type-1 (HIV-1) continues to evolve in presence of broadly neutralizing antibodies more than ten years after infection.
Get PDFThe evolution of HIV-1 and its immune escape to autologous neutralizing antibodies (Nabs) during the acute/early phases of infection have been analyzed in depth in many studies. In contrast, little is known about neither the long-term evolution of the virus in patients who developed broadly Nabs (bNabs) or the mechanism of escape in presence of these bNabs
Predictors of breastfeeding cessation among HIV infected mothers in Southern Ethiopia: a survival analysis.
No full textBACKGROUND: Mother-to-child transmission (MTCT) of Human immunodeficiency virus (HIV) through breastfeeding remains the most significant route infection among children. Although the current guideline is recommending continued breastfeeding for HIV exposed infants, significant proportion of infants have been subjected to early weaning to prevent HIV transmission. However the predictors of breastfeeding cessation among HIV positive mothers were not documented in Ethiopia. Therefore the objective of this study was to determine the predictors of breastfeeding cessation among HIV-infected women in Southern Ethiopia. METHODS: A facility based cross sectional study was conducted in Southern Ethiopia. The samples were selected by cluster sampling technique. The Kaplan-Meier curve was used to describe the survival time of breastfeeding and a step-wise multivariable Cox-proportional hazards regression model were used to identify the predictors of breastfeeding cessation. Both crude and adjusted hazard ratio were determined and p<0.05 was considered as statistically significant. RESULT: The mean duration of breastfeeding among HIV positive mothers was 13.79 [95% CI: (12.97-14.59)] months. The Kaplan-Meier estimate showed that proportions of women who were breastfeeding at 6, 9, 12 and 17 months were 89.3%, 75.3%, 66% and 17%, respectively. Those mothers having a monthly income of ≤ 500 ETB [AHR = 0.16, 95% CI :(0.03-0.76)], having a family size of three and below [AHR = 0.12, 95%CI: (0.02-0.68), four and above [AHR = 0.07, 95%CI: (0.01-0.35)] and bottle feeding [AHR = 3.95, 95%CI: (1.64-9.51)] were also independent factors associated with breastfeeding cessation. CONCLUSION: Above one third of HIV positive mothers stopped breastfeeding before 12 months. Monthly income, bottle feeding and family size were the independent predictors of breastfeeding cessations. Strengthening the current counseling and promotion modality on avoidance of bottle feeding and continued breastfeeding is recommended for improved HIV free survival
Cerebrospinal fluid (CSF) CD8+ T-cells that express interferon-gamma contribute to HIV associated neurocognitive disorders (HAND).
Get PDFBackgroundHIV associated neurocognitive disorders (HAND) continue to affect cognition and everyday functioning despite anti-retroviral treatment (ART). Previous studies focused on mechanisms related to monocyte/macrophage mediated inflammation. However, in the ART era, there is increasing evidence for the involvement of CD8+ T-cells in CNS pathogenesis.MethodsTo investigate the relationship between T-cell responses and neurocognitive impairment (NCI), cerebrospinal fluid (CSF) and peripheral blood CD4+ and CD8+ T-cell intracellular cytokine (IFNγ, IL-2, TNFα) and lytic marker (CD107a) expression were assessed in HIV infected subjects who underwent comprehensive neurocognitive (NC) evaluation and either initiated or changed ART.ResultsData were collected from 31 participants at 70 visits. The frequency of cytokine expressing T-cells in CSF was significantly higher than in peripheral blood for CD4+T-cells: TNFα, IL-2, IFNγ and CD8+T-cells: IL-2 and IFNγ. Analysis of T-cell activity and NCI as a function of CSF HIV RNA levels suggested a general association between NCI, high CSF CD8+ (but not CD4+T-cell) cytokine expression and CSF HIV RNA 400/μl and low CSF HIV RNA levels (ConclusionsPresence of IFNγ expressing CD8+ T-cells, absence of cytolytic CD8+ T-cells, high myeloid activation, and failure of ART to suppress HIV replication in CSF contribute to increased risk of HAND
p21(WAF1/CIP1) RNA expression in highly HIV-1 exposed, uninfected individuals.
Get PDFSome individuals remain HIV-1 antibody and PCR negative after repeated exposures to the virus, and are referred to as HIV-exposed seronegatives (HESN). However, the causes of resistance to HIV-1 infection in cases other than those with a homozygous CCR5Δ32 deletion are unclear. We hypothesized that human p21WAF1/CIP1 (a cyclin-dependent kinase inhibitor) could play a role in resistance to HIV-1 infection in HESN, as p21 expression has been associated with suppression of HIV-1 in elite controllers and reported to block HIV-1 integration in cell culture. We measured p21 RNA expression in PBMC from 40 HESN and 40 low exposure HIV-1 seroconverters (LESC) prior to their infection using a real-time PCR assay. Comparing the 20 HESN with the highest exposure risk (median = 111 partners/2.5 years prior to the 20 LESC with the lowest exposure risk (median = 1 partner/2.5 years prior), p21 expression trended higher in HESN in only one of two experiments (P = 0.11 vs. P = 0.80). Additionally, comparison of p21 expression in the top 40 HESN (median = 73 partners/year) and lowest 40 LESC (median = 2 partners/year) showed no difference between the groups (P = 0.84). There was a weak linear trend between risk of infection after exposure and increasing p21 gene expression (R2 = 0.02, P = 0.12), but again only in one experiment. Hence, if p21 expression contributes to the resistance to viral infection in HESN, it likely plays a minor role evident only in those with extremely high levels of exposure to HIV-1
Characteristics of decidual macrophages and Hofbauer cells in placentas of HIV positive women on antiretroviral therapy
Get PDFMacrophages are the most abundant immune cells at the maternal-foetal interface of term placentas. They play a role in regulating pregnancy, promoting immunological tolerance, and maintaining a homeostatic environment crucial for foetal development. Numerous studies have reported the dysregulation of maternal uterine-derived macrophages, the decidual macrophages and the foetal placental-derived macrophages, the Hofbauer Cells (HCs) in pregnancies complicated by maternal viral infections. The immune mechanisms associated with the high prevalence of adverse birth outcomes amongst HIV-1 infected women on combination antiretroviral therapy (ART) are not well characterized. In this Ph.D. dissertation, the impact of HIV-1 infection and the duration of ART exposure on the phenotype and function of decidual macrophages and HCs was studied. Birth outcomes and placenta pathologies of HIVinfected women categorized into two groups, 1). HIV-1 infected pregnant women who initiated ART during pregnancy (Initiating ART n=16); and 2). HIV-1 infected women who initiated ART before pregnancy (Stable on ART n=14) were compared. Immunohistochemical and immunofluorescence staining of formalin-fixed placental tissues from the two groups was performed to compare the expression of macrophage markers associated with inflammation (M1) and immune regulation (M2). Lastly, the Human Protein Atlas database was used to identify novel markers of decidual macrophages and HCs and their potential biomarkers of HIV-1 infection. The expression of various M1 and M2-specific macrophage markers significantly varied between membranes of the maternal-foetal interface within the initiating and stable group. The duration of ART exposure had no effect on the expression of typical M1 and M2 macrophage markers on decidual macrophages and HCs of HIV-1 infected women who initiated a similar ART regimen before pregnancy and during pregnancy. The macrophage populations in the maternal-foetal interface co-expressed markers associated with M1 and M2 macrophage polarisation, suggesting functional plasticity of these cells. Human Coagulation Factor XIIIa1 (FXIIIa1) and Insulin-like growth factor 2 (IGF2) were identified as potential novel markers of HCs and decidual macrophages respectively, however, further validation is required. There is a paucity of data on the characteristics of decidual macrophages and Hofbauer cells in both normal and complicated pregnancies. Data presented in this dissertation suggests the possibility that HIV-infection and / the duration of ART exposure may not play an active role in dysregulating immune mechanisms associated with macrophages at the maternal-foetal interface. However, further characterization of these cells in placentas exposed to different ART regimens is required using the novel markers discovered in this Ph.D
Elevated soluble triggering receptor expressed on myeloid cells (sTREM)-1 levels in maternal serum during term and preterm labor
Get PDFBackground: Infection and inflammation are important mechanisms leading to preterm birth. Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) belongs to a family of cell surface receptors that seems to play an important role in fine-tuning the immune response. It has been demonstrated that sTREM-1 is involved in bacterial infection as well as in noninfectious inflammatory conditions. Few studies have investigated serum sTREM-1 expression during preterm labor. Therefore, the purpose of this study was to assess sTREM-1 concentrations in maternal serum during term and preterm labor.
Methods: This case control study included 176 singleton pregnancies in the following groups: patients in (1) preterm labor, delivered before 34 weeks (PTB) (n = 52); (2) GA matched controls, not in labor, matched for gestational age (GA) with the PTB group (n = 52); (3) at term in labor (n = 40) and (4) at term not in labor (n = 32). sTREM-1 concentrations were determined by enzyme-linked immunoassay.
Results: sTREM-1 was detected in all serum samples. Median sTREM-1 concentrations were significantly higher in women with PTB vs. GA matched controls (367 pg/ml, interquartile range (IQR) 304-483 vs. 273 pg/ml, IQR 208-334; P < 0.001) and in women at term in labor vs. at term not in labor (300 pg/ml, IQR 239-353 vs. 228 pg/ml, IQR 174-285; P < 0.001). Women with PTB had significantly higher levels of sTREM-1 compared to women at term in labor (P = 0.004). Multiple regression analysis, with groups recoded as three key covariates (labor, preterm and rupture of the membranes), showed significantly higher sTREM-1 concentrations for labor (+30%, P < 0.001) and preterm (+15%, P = 0.005) after adjusting for educational level, history of PTB and sample age.
Conclusions: sTREM-1 concentrations in maternal serum were elevated during spontaneous term and preterm labor and sTREM-1 levels were significantly higher in preterm labor
Equivalent T cell epitope promiscuity in ecologically diverse human pathogens.
Get PDFThe HLA (human leukocyte antigen) molecules that present pathogen-derived epitopes to T cells are highly diverse. Correspondingly, many pathogens such as HIV evolve epitope variants in order to evade immune recognition. In contrast, another persistent human pathogen, Mycobacterium tuberculosis, has highly conserved epitope sequences. This raises the question whether there is also a difference in the ability of these pathogens' epitopes to bind diverse HLA alleles, referred to as an epitope's binding promiscuity. To address this question, we compared the in silico HLA binding promiscuity of T cell epitopes from pathogens with distinct infection strategies and outcomes of human exposure.We used computer algorithms to predict the binding affinity of experimentally-verified microbial epitope peptides to diverse HLA-DR, HLA-A and HLA-B alleles. We then analyzed binding promiscuity of epitopes derived from HIV and M. tuberculosis. We also analyzed promiscuity of epitopes from Streptococcus pyogenes, which is known to exhibit epitope diversity, and epitopes of Bacillus anthracis and Clostridium tetani toxins, as these bacteria do not depend on human hosts for their survival or replication, and their toxin antigens are highly immunogenic human vaccines.We found that B. anthracis and C. tetani epitopes were the most promiscuous of the group that we analyzed. However, there was no consistent difference or trend in promiscuity in epitopes contained in HIV, M. tuberculosis, and S. pyogenes.Our results show that human pathogens with distinct immune evasion strategies and epitope diversities exhibit equivalent levels of T cell epitope promiscuity. These results indicate that differences in epitope promiscuity do not account for the observed differences in epitope variation and conservation
- …
