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Daniel Kondziella,Siska Frahm-Falkenberg 대한신경과학회 2011 Journal of Clinical Neurology Vol.7 No.2
Anton’s syndrome is arguably the most striking form of anosognosia. Patients with this syndrome behave as if they can see despite their obvious blindness. Although best known for his description of asomatognosia and visual anosognosia, Gabriel Anton (1858-1933) made other significant contributions to the clinical neurosciences, including pioneering work in neurosurgery, neuropsychology, and child psychiatry. However, it has not been recognized in the English literature that Anton was also a dedicated advocate of eugenics and racial hygiene. This paper provides a case of Anton’s syndrome and puts the works of Gabriel Anton into their historic context.
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Huang, Yunda,Zhang, Lily,Janes, Holly,Frahm, Nicole,Isaacs, Abby,Kim, Jerome H.,Montefiori, David,McElrath, M. Julie,Tomaras, Georgia D.,Gilbert, Peter B. Elsevier 2017 Vaccine Vol.35 No.8
<P><B>Abstract</B></P> <P><B>Background</B></P> <P>The evaluation of durable immune responses is important in HIV vaccine research and development. The efficiency of such evaluation could be increased by incorporating predictors of the responses in the statistical analysis. In this paper, we investigated whether and how baseline demographic variables and immune responses measured two weeks after vaccination predicted durable immune responses measured six months later.</P> <P><B>Methods</B></P> <P>We included data from seven preventive HIV vaccine regimens evaluated in three clinical trials: a Phase 1 study of four DNA, NYVAC and/or AIDSVAX vaccine regimens (HVTN096), a Phase 2 study of two DNA and/or MVA vaccine regimens (HVTN205), and a Phase 3 study of a single ALVAC/AIDSVAX regimen (RV144). Regularized random forests and linear regression models were used to identify and evaluate predictors of the positivity and magnitude of durable immune responses.</P> <P><B>Results</B></P> <P>We analyzed 201 vaccine recipients with data from 10 to 127 immune response biomarkers, and 3–5 demographic variables. The best prediction of participants’ durable response positivity based on two-week responses rendered up to close-to-perfect accuracy; the best prediction of participants’ durable response magnitude rendered correlation coefficients between the observed and predicted responses ranging up to 0.91. Though prediction performances differed among biomarkers, durable immune responses were best predicted by the two-week response level of the same biomarker. Adding demographic information and two-week response levels of different biomarkers provided little or no improvement in the predictions.</P> <P><B>Conclusions</B></P> <P>For some biomarkers and for the vaccines we studied, two-week post-vaccination responses can well predict durable responses six months later. Therefore, if immune response durability is only assessed in a sub-sample of vaccine recipients, statistical analyses of durable responses will have increased efficiency by incorporating two-week response data. Further research is needed to generalize the findings to other vaccine regimens and biomarkers.</P> <P>Clinicaltrials.gov identifiers: NCT01799954, NCT00820846, NCT00223080.</P> <P><B>Highlights</B></P> <P> <UL> <LI> HIV vaccine-induced immune responses at 2weeks predict those 6months later. </LI> <LI> The former responses can increase evaluation efficiency of vaccine durability. </LI> <LI> The former responses of the same biomarker best predict the latter. </LI> <LI> Demographics and responses of other biomarkers add little for prediction. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
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Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection
Auclair, Sarah,Liu, Fengliang,Niu, Qingli,Hou, Wei,Churchyard, Gavin,Morgan, Cecilia,Frahm, Nicole,Nitayaphan, Sorachai,Pitisuthithum, Punnee,Rerks-Ngarm, Supachai,Kimata, Jason T.,Soong, Lynn,Franchi Public Library of Science 2018 PLoS pathogens Vol.14 No.2
<▼1><P>The concerns raised from adenovirus 5 (Ad5)-based HIV vaccine clinical trials, where excess HIV infections were observed in some vaccine recipients, have highlighted the importance of understanding host responses to vaccine vectors and the HIV susceptibility of vector-specific CD4 T cells in HIV vaccination. Our recent study reported that human Ad5-specific CD4 T cells induced by Ad5 vaccination (RV156A trial) are susceptible to HIV. Here we further investigated the HIV susceptibility of vector-specific CD4 T cells induced by ALVAC, a canarypox viral vector tested in the Thai trial RV144, as compared to Ad5 vector-specific CD4 T cells in the HVTN204 trial. We showed that while Ad5 vector-specific CD4 T cells were readily susceptible to HIV, ALVAC-specific CD4 T cells in RV144 PBMC were substantially less susceptible to both R5 and X4 HIV <I>in vitro</I>. The lower HIV susceptibility of ALVAC-specific CD4 T cells was associated with the reduced surface expression of HIV entry co-receptors CCR5 and CXCR4 on these cells. Phenotypic analyses identified that ALVAC-specific CD4 T cells displayed a strong Th1 phenotype, producing higher levels of IFN-γ and CCL4 (MIP-1β) but little IL-17. Of interest, ALVAC and Ad5 vectors induced distinct profiles of vector-specific CD8 vs. CD4 T-cell proliferative responses in PBMC, with ALVAC preferentially inducing CD8 T-cell proliferation, while Ad5 vector induced CD4 T-cell proliferation. Depletion of ALVAC-, but not Ad5-, induced CD8 T cells in PBMC led to a modest increase in HIV infection of vector-specific CD4 T cells, suggesting a role of ALVAC-specific CD8 T cells in protecting ALVAC-specific CD4 T cells from HIV. Taken together, our data provide strong evidence for distinct HIV susceptibility of CD4 T cells induced by different vaccine vectors and highlight the importance of better evaluating anti-vector responses in HIV vaccination.</P></▼1><▼2><P><B>Author summary</B></P><P>Development of a safe and efficacious HIV vaccine is a critical global health priority. Recombinant viral vectors are an important platform for HIV vaccine delivery. Recent clinical trials testing candidate HIV vaccines based on Ad5 vectors failed and reported excess HIV infections in some vaccine recipients, underscoring the necessity to investigate HIV susceptibility of viral vector-specific CD4 T cells in HIV vaccination. By using PBMC samples from clinical trials that examined two important HIV vaccine vectors (canarypox viral vector ALVAC and human Ad5 vector), we here report that compared to Ad5 vector, the ALVAC-specific CD4 T cells are more resistant to HIV infection, providing evidence for distinct HIV susceptibility of CD4 T-cell populations induced by different HIV vaccine vectors. Our findings present new insights into our understanding of HIV vaccine-induced immunity and help improve the design and immune assessment of viral vectors for the development of HIV vaccines.</P></▼2>
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