95 research outputs found
La anorexia por actividad desde el punto de vista del análisis experimental del comportamiento
No full textEn este artículo se describe el síndrome de anorexia en humanos. Se analiza la similitud funcional entre el modelo animal de actividad anorexia y patología humana. Además, se describe la teoría de la actividad de la anorexia por Epling y Pierce (1992) para mostrar el desarrollo de esta patología en humanos. También se presentan las teorías más relevantes que han tratado de explicar el origen de la anorexia de actividad. Por último, se resume el análisis experimental de la contribución del comportamiento a la evaluación y el tratamiento de la anorexia de actividad en humanos.In this paper anorexia syndrome in humans is described. Functional similarity between an animal model of activity anorexia and human pathology are analyzed. Moreover, abiobehavioral theory of activity anorexia by Epling and Pierce (1992) is described to showdevelopment of this pathology in humans. The most relevant theories which have tried toexplain the origin of activity anorexia are presented, too. At last, experimental analysis ofbehavior contribution to the evaluation and treatment for activity anorexia in humans areoutlined
Exploiting knowledge of immune selection in HIV-1 to detect HIV-specific CD8 T-cell responses
No full textSince HLA-restricted cytotoxic T-cell responses select specific polymorphisms in HIV-1 sequences and HLA diversity is relatively static in human populations, we investigated the use of peptide epitopes based on sites of HLA-associated adaptation in HIV-1 sequences to stimulate and detect T-cell responses ex vivo. These "HLA-optimised" peptides captured more HIV-1 Nef-specific responses compared with overlapping peptides of a single consensus sequence, in interferon-γ enzyme linked immunospot assays. Sites of immune selection can reveal more immunogenic epitopes in HLA-diverse populations and offer insights into the nature of HLA-epitope targeting, which could be applied in vaccine design
IL-2 Immunotherapy to Recently HIV-1 Infected Adults Maintains the Numbers of IL-17 Expressing CD4+ T (TH17) Cells in the Periphery
No full textLittle is known about the manipulation of IL-17 producing CD4+ T cells (TH17) on a per-cell basis in humans in vivo. Previous studies on the effects of IL-2 on IL-17 secretion in non-HIV models have shown divergent results. We hypothesized that IL-2 would mediate changes in IL-17 levels among recently HIV-1-infected adults receiving anti-retroviral therapy. We measured cytokine T cell responses to CD3/CD28, HIV-1 Gag, and CMV pp65 stimulation, and changes in multiple CD4+ T cell subsets. Those who received IL-2 showed a robust expansion of naive and total CD4+ T cell counts and T-reg counts. However, after IL-2 treatment, the frequency of TH17 cells declined, while counts of TH17 cells did not change due to an expansion of the CD4+ naïve T cell population (CD27+CD45RA+). Counts of HIV-1 Gag-specific T cells declined modestly, but CMV pp65 and CD3/CD28 stimulated populations did not change. Hence, in contrast with recent studies, our results suggest IL-2 is not a potent in vivo regulator of TH17 cell populations in HIV-1 disease. However, IL-2-mediated T-reg expansions may selectively reduce responses to certain antigen-specific populations, such as HIV-1 Gag
Flow cytometric quantification of surface IGF-1R and intracellular p-AKT, p-S6, and p-ERK in Ewing sarcoma (EWS) cells.
No full text 23 Background: Targeting the IGF-1R pathway has shown preclinical and clinical evidence of activity in EWS. Markers predictive of response to IGF-1R inhibition are required. The aims of the current study were to quantify surface IGF-1R expression and intracellular signaling proteins by flow cytometry. Methods: Flow cytometry for CD99 and CD45 was used to detect bone marrow micrometastatic tumor cells as CD99+CD45- events in patients with localized EWS. Surface IGF-1R was quantified on tumor cells and normal marrow cells using a commercially available antibody. RD-ES EWS cells were spiked into control PBMCs and starved for 1 hour. Cells were then treated with saline control, rapamycin 10 ng/mL, ADW742 5 uM (small molecule IGF-1R inhibitor), or alpha-IR3 0.5 ug/mL (anti-IGF-1R antibody) and levels of pS6, pAKT, and pERK quantified by phospho-flow cytometry 60 minutes later. All results were expressed as the mean fluorescent intensity (MFI) of staining using arbitrary units. Results: We detected bone marrow micrometastatic tumor cells in marrow samples from 16 patients with EWS. We observed heterogeneous levels of IGF-1R tumor cell surface expression between patients (range of IGF-1R MFI = 0 – 3355). IGF-1R levels were higher in CD99+CD45- tumor cells compared to normal marrow cells (mean MFI 840 for CD99+CD45- tumor cells vs.190 for normal marrow cells; p = 0.005). In RD-ES cells spiked into PBMCs, treatment with rapamycin resulted in 1.32 fold increase in pAKT MFI compared to saline control. Treatment with ADW742 or alpha-IR3 did not impact pAKT MFI. Treatment with rapamycin resulted in a 0.52 fold decrease and a 1.20 fold increase in pS6 and pERK, respectively. Treatment with ADW742 or alpha-IR3 each resulted in similar decreases in both pS6 (0.75-0.87 fold) and pERK (0.67-0.82 fold). In PBMCs, modest changes in pS6 in rapamycin treated cells were observed, without changes in pAKT or pERK. Neither ADW742 nor alpha-IR3 modulated pS6, pAKT, or pERK signaling in PBMCs. Conclusions: Flow cytometry detects a range of surface IGF-1R expression on bone marrow micrometastatic EWS cells. Phospho-flow cytometry detects modulation of pAKT, pS6, and pERK in EWS cells treated with IGF-1R or mTOR inhibitors. </jats:p
Phylogenetische und taxonomische Untersuchungen an der Subtribus Menthinae (Lamiaceae, Nepetoideae, Mentheae) unter besonderer Berücksichtigung des Satureja-Komplexes
No full textCMV Antigen-Specific CD4<SUP>+</SUP> and CD8<SUP>+</SUP> T Cell IFNγ Expression and Proliferation Responses in Healthy CMV-Seropositive Individuals
No full textHigh CD8+ T cell activation marks a less differentiated HIV-1 specific CD8+ T cell response that is not altered by suppression of viral replication.
No full textThe relationship of elevated T cell activation to altered T cell differentiation profiles, each defining features of HIV-1 infection, has not been extensively explored. We hypothesized that anti-retroviral suppression of T cell activation levels would lead to alterations in the T cell differentiation of total and HIV-1 specific CD8+ T cell responses among recently HIV-1 infected adults.We performed a longitudinal study simultaneously measuring T cell activation and maturation markers on both total and antigen-specific T cells in recently infected adults: prior to treatment; after the initiation of HAART; and after treatment was halted. Prior to treatment, HIV-1 Gag-specific CD8+ T cells were predominantly of a highly activated, intermediate memory (CD27+CD28-) phenotype, while CMV pp65-specific CD8+ T cells showed a late memory (CD27-CD28-), low activation phenotype. Participants with the highest fraction of late memory (CD27-CD28-) HIV-1-specific CD8+ T cells had higher CD4+ T cell counts (rho = +0.74, p = 0.004). In turn, those with the highest fraction of intermediate memory (CD27+ CD28-) HIV-1 specific CD8+ T cells had high total CD8+ T cell activation (rho = +0.68, p = 0.01), indicating poorer long-term clinical outcomes. The HIV-1 specific T cell differentiation profile was not readily altered by suppression of T cell activation following HAART treatment.A more differentiated, less activated HIV-1 specific CD8+ T cell response may be clinically protective. Anti-retroviral treatment initiated two to four months after infection lowered T cell activation but had no effect on the differentiation profile of the HIV-1-specific response. Intervention during the first month of acute infection may be required to shift the differentiation phenotype of HIV-1 specific responses to a more clinically favorable profile
Evidence-based medicine culture, curriculum, and program outcomes: A CERA study
No full textBackground:Limited faculty development is a barrier to advancing evidence-based medicine (EBM) education. This study sought to describe program director perception of EBM culture in family medicine residency training and to assess the association among structured faculty roles, EBM curricula, and specific resident outcomes including publications in EBM.
Methods:Members of the Society of Teachers of Family Medicine EBM collaborative drafted survey questions based on a literature review. The questions were electronically distributed in May 2023 to all US family medicine residency program directors who had not previously opted out by the Council of Academic Family Medicine Educational Research Alliance within its study of family medicine program directors. We analyzed results using descriptive and comparative statistics.
Results:The overall response rate was 44.7% (309/691). We found that 260/281 (92%) of program directors reported an EBM curriculum of some kind, and 253/281 (90%) of program directors agreed/strongly agreed that EBM was accepted by residents. Of the respondents, 72/281 (25.6%) reported that no specific faculty member was responsible for their EBM curriculum. Most program directors reported that less than 50% of residents will leave their programs with the ability to detect an error in original research (23.8%; 67/281), detect an important omission in an UpToDate article (16%; 45/281), or author a narrative review for American Family Physician (10%; 28/281).
Conclusions:Program directors reported strong acceptance of EBM among residents and a high prevalence of a formal curriculum. However, many lacked a specific faculty lead, and few reported that residents had strong EBM skills. This study identified gaps in residency training to support future EBM-skilled family physicians as well as concerns about pathways for the development of future EBM faculty
Safety and immunogenicity of Towne cytomegalovirus vaccine with or without adjuvant recombinant interleukin-12
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