scholarly journals Age-dependent decreases in mitogen-stimulation level and RNA content in peripheral blood mononuclear cells of down syndrome patients

2006 ◽  
Vol 72B (1) ◽  
pp. 43-48 ◽  
Author(s):  
Zuhal Hamurcu ◽  
Halil Demirtas ◽  
Turkan Patiroglu ◽  
Sefer Kumandas ◽  
Nalan Imamoglu ◽  
...  
Author(s):  
R L Jeon ◽  
C Gilbert ◽  
J Cheng ◽  
A M Putz ◽  
M K Dyck ◽  
...  

Abstract Disease resilience refers to productivity of an animal under disease. Given the high biosecurity of pig nucleus herds, traits that can be measured on healthy pigs and that are genetically correlated with disease resilience, i.e. genetic indicator traits, offer a strategy to select for disease resilience. Our objective was to evaluate mitogen stimulation assays on peripheral blood mononuclear cells from young healthy pigs as genetic indicators for disease resilience. Data were from a natural disease challenge in which batches of 60 or 75 naïve Yorkshire x Landrace piglets were introduced every three weeks into a continuous flow barn that was seeded with multiple diseases. In this environment, disease resilience traits, including growth, treatment, and mortality rates, were recorded on 3136 pigs that were genotyped with a high-density marker panel. Peripheral blood mononuclear cells from 882 of these pigs from 19 batches were isolated from whole blood collected prior to the disease challenge and stimulated with five mitogens: concanavalin A (ConA), phytohemagglutinin (PHA), pokeweed mitogen (PWM), lipopolysaccharide (LPS), and phorbol myristate acetate (PMA). Proliferation of cells was evaluated at 48, 72, and 96 hrs and compared to unstimulated samples (rest count). Heritabilities of cell proliferation were estimated using a model with batch as a fixed effect, covariates of entry age, rest count, and complete blood count proportions of lymphocytes, monocytes, eosinophils, and basophils, and pen, litter, and animal genetics as random effects. Heritability estimates were highest for response to ConA (0.30+0.09, 0.28+0.10, 0.17+0.10, and 0.25+0.10 at 48, 72, and 96 hrs after stimulation and for area under the curve across the three time points, respectively). Estimates were in a similar range for response to PHA and PMA, but low for PWM and LPS. Responses to ConA, PHA, and PMA were moderately genetically correlated with several disease resilience traits and in the expected direction but individual estimates were not significantly different from zero due to large standard errors. In conclusion, although validation is needed, mitogen stimulation assays, in particular based on ConA, show promise as genetic indicator traits for disease resilience.


Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1112
Author(s):  
Chiara Lanzillotta ◽  
Viviana Greco ◽  
Diletta Valentini ◽  
Alberto Villani ◽  
Valentina Folgiero ◽  
...  

Down syndrome (DS) is the most common chromosomal disorder and the leading genetic cause of intellectual disability in humans, which results from the triplication of chromosome 21. To search for biomarkers for the early detection and exploration of the disease mechanisms, here, we investigated the protein expression signature of peripheral blood mononuclear cells (PBMCs) in DS children compared with healthy donors (HD) by using an in-depth label-free shotgun proteomics approach. Identified proteins are found associated with metabolic pathways, cellular trafficking, DNA structure, stress response, cytoskeleton network, and signaling pathways. The results showed that a well-defined number of dysregulated pathways retain a prominent role in mediating DS pathological features. Further, proteomics results are consistent with published study in DS and provide evidences that increased oxidative stress and the increased induction of stress related response, is a participant in DS pathology. In addition, the expression levels of some key proteins have been validated by Western blot analysis while protein carbonylation, as marker of protein oxidation, was investigated. The results of this study propose that PBMCs from DS children might be in an activated state where endoplasmic reticulum stress and increased production of radical species are one of the primary events contributing to multiple DS pathological features.


1987 ◽  
Vol 7 (8) ◽  
pp. 2988-2993
Author(s):  
H E Broome ◽  
J C Reed ◽  
E P Godillot ◽  
R G Hoover

Transcription of the c-myc gene is initiated from two principal promoters, P1 and P2. We demonstrate here that a shift in promoter utilization occurred with time in human peripheral blood mononuclear cells (PBMC) that had been stimulated to proliferate. The P1/P2 ratio reached a maximum of approximately 1.3 at 4 h after phytohemagglutinin stimulation and a minimum of 0.31 at 48 h. Actinomycin decay experiments demonstrated that both P1 and P2 transcripts had similar half-lives at early and late times after mitogen stimulation, indicating that the shift in promoter utilization was probably not posttranscriptionally regulated. Addition of interleukin-2 to previously activated PBMC increased c-myc mRNA, but unlike increases after mitogen stimulation, the P1/P2 ratio stayed less than 0.5. Our findings demonstrated that there was a difference between mitogen- and interleukin-2-stimulated increases in c-myc RNA in PBMC.


Sign in / Sign up

Export Citation Format

Share Document