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Publications

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Title:
Simultaneous Quantification of Plasmodium Antigens and Host Factor C-Reactive Protein in Asymptomatic Individuals with Confirmed Malaria by Use of a Novel Multiplex Immunoassay

Publication:
J Clin Microbiol 57:e00948-18.

Author(s):
Ihn Kyung Jang, Abby Tyler, Chris Lyman, et al.

Quansys Products Used:
Q-Plex™ Human Malaria Array Kit, Q-View Imager Pro, and Q-View Software

Abstract:

Malaria rapid diagnostic tests (RDTs) primarily detect Plasmodium falciparum antigen histidine-rich protein 2 (HRP2) and the malaria-conserved antigen lactate dehydrogenase (LDH) for P. vivax and other malaria species. The performance of RDTs and their utility is dependent on circulating antigen concentration distributions in infected individuals in a population in which malaria is endemic and on the limit of detection of the RDT for the antigens. A multiplexed immunoassay for the quantification of HRP2, P. vivax LDH, and all-malaria LDH (pan LDH) was developed to accurately measure circulating antigen concentration and antigen distribution in a population with endemic malaria. The assay also measures C-reactive protein (CRP) levels as an indicator of inflammation. Validation was conducted with clinical specimens from 397 asymptomatic donors from Myanmar and Uganda, confirmed by PCR for infection, and from participants in induced blood-stage malaria challenge studies. The assay lower limits of detection for HRP2, pan LDH, P. vivax LDH, and CRP were 0.2 pg/ml, 9.3 pg/ml, 1.5 pg/ml, and 26.6 ng/ml, respectively. At thresholds for HRP2, pan LDH, and P. vivax LDH of 2.3 pg/ml, 47.8 pg/ml, and 75.1 pg/ml, respectively, and a specificity 98.5%, the sensitivities for ultrasensitive PCR-confirmed infections were 93.4%, 84.9%, and 48.9%, respectively. Plasmodium LDH (pLDH) concentration, in contrast to that of HRP2, correlated closely with parasite density. CRP levels were moderately higher in P. falciparum infections with confirmed antigenemia versus those in clinical specimens with no antigen. The 4-plex array is a sensitive tool for quantifying diagnostic antigens in malaria infections and supporting the evaluation of new ultrasensitive RDTs.

 

Title:

Disruption of retinal pigment epithelial cell properties under the exposure of cotinine 

Publication:
Sci Rep 2017: doi.org/10.1038/s41598-017-03283-x

Author(s):
Xiao-Yu Zhang, Tsz Kin Ng, Mårten Erik Brelén, et al.

Quansys Products Used:
Human Angiogenesis Q-Plex Array Kit and Q-View Software

Abstract:

Cigarette smoking is a major risk factor for age-related macular degeneration (AMD), in which progressive retinal pigment epithelial (RPE) cell degeneration is a major pathological change. Nicotine is a major biologically active component in cigarette smoke. It is continuously catabolized into cotinine, which has longer half-life and higher concentration in tissue cells and fluids. Here we hypothesized that continuous exposure of cotinine has more potent effects on human RPE cell properties than nicotine. Human RPE cell line (ARPE-19) was treated continuously with 1–2 µM of nicotine and/or cotinine for 7 days. RPE cells treated with 2 μM cotinine and nicotine-cotinine mixture has lower MTT signals without significant changes in cell apoptosis or integrity. Moreover, RPE cell migration was retarded under cotinine treatments, but not nicotine. Both nicotine and cotinine treatments attenuated the phagocytotic activity of RPE cells. In addition, cotinine and nicotine-cotinine mixture suppressed VEGF and IL-8 expression and upregulated TIMP-2 expression. Expressions of autophagy genes were upregulated by the cotinine treatment, whereas expressions of epithelial-to-mesenchymal transition markers were downregulated. In conclusion, our study, for the first time, demonstrated that cotinine, rather than nicotine, affects the properties of RPE cells in vitro, which could explain the smoking-induced RPE pathology.

 

Title:
Multiplex serum protein analysis reveals potential mechanisms and markers of response to hyperimmune caprine serum in systemic sclerosis 

Publication:
Arthritis Research & Therapy 2017: doi.org/10.1186/s13075-017-1252-x

Author(s):
Niamh Quillinan, Kristina E. N. Clark, Bryan Youl, et al.

Quansys Products Used:
Human Angiogenesis Q-Plex Array Kit

Abstract:

Hyperimmune caprine serum (HICS) is a novel biological therapy with potential benefit for skin in established diffuse cutaneous systemic sclerosis. Here we report multiplex protein analysis of blood samples from a placebo-controlled phase II clinical trial and explore mechanisms of action and markers of response.

 

Title:
Child mortality, hypothalamic-pituitary-adrenal axis activity and cellular aging in mothers 

Publication:
PLOS ONE 2017: doi.org/10.1371/journal.pone.0177869

Author(s):
Cindy K. Barha, Katrina G. Salvante, Courtney W. Hanna, et al.

Quansys Products Used:
Immunoassay Array

Abstract:

Psychological challenges, including traumatic events, have been hypothesized to increase the age-related pace of biological aging. Here we test the hypothesis that psychological challenges can affect the pace of telomere attrition, a marker of cellular aging, using data from an ongoing longitudinal-cohort study of Kaqchikel Mayan women living in a population with a high frequency of child mortality, a traumatic life event. Specifically, we evaluate the associations between child mortality, maternal telomere length and the mothers’ hypothalamic-pituitary-adrenal axis (HPAA), or stress axis, activity. Child mortality data were collected in 2000 and 2013. HPAA activity was assessed by quantifying cortisol levels in first morning urinary specimens collected every other day for seven weeks in 2013. Telomere length (TL) was quantified using qPCR in 55 women from buccal specimens collected in 2013. Results: Shorter TL with increasing age was only observed in women who experienced child mortality (p = 0.015). Women with higher average basal cortisol (p = 0.007) and greater within-individual variation (standard deviation) in basal cortisol (p = 0.053) presented shorter TL. Non-parametric bootstrapping to estimate mediation effects suggests that HPAA activity mediates the effect of child mortality on TL. Our results are, thus, consistent with the hypothesis that traumatic events can influence cellular aging and that HPAA activity may play a mediatory role. Future large-scale longitudinal studies are necessary to confirm our results and further explore the role of the HPAA in cellular aging, as well as to advance our understanding of the underlying mechanisms involved.

 

Title:
Changes of Th1/Th2 cytokines in patients with primary hepatocellular carcinoma after ultrasound-guided ablation 

Publication:
Int J Clin Exp Pathol, 2017

Author(s):
Lili Ji, Jun Gu, Lei Chen, et al.

Quansys Products Used:
Quansys Human 9-Plex Assay and Q-View Software

Abstract:

Liver cancer is a malignancy of the digestive system and has a high morbidity and mortality rate. Local intervention has become a viable option in identifying liver treatment. The aim of the present study was to analyze the changes of Th1/Th2 cytokines in patients with primary hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) treatment. 26 patients with stage III-IV liver cancers and 25 healthy controls were selected to participate in the study. HCC patients were initiated with RFA treatment and the serum levels of alpha fetoprotein (AFP) and Th1/Th2 cytokines were valued. We found that with the level of AFP decreased, the levels of Th1 cytokines including interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were significantly increased after treatment with RFA (P<0.05). Meanwhile, the levels of Th2 cytokines consist of interleukin-4 (IL-4), IL-6 and IL-10 were decreased markedly on the contrary, and the differences were statistically significant (P<0.05). In conclusion, the levels of Th1/Th2 cytokines were correlated with the change of AFP in patients of HCC after treatment with RFA, which might be an important guiding significance for the prognosis of HCC.

 

Title:
Anti-inflammatory and anti-apoptotic effects of rosuvastatin by regulation of oxidative stress in a dextran sulfate sodium-induced colitis model 

Publication:
World J Gastroenterol, 2017: doi.org/10.3748/wjg.v23.i25.4559

Author(s):
Seung Kak Shin, Jae Hee Cho, Eui Joo Kim, et al.

Quansys Products Used:
Mouse Cytokine Array

Abstract:

Aim: To evaluate the anti-inflammatory and anti-apoptotic effects of rosuvastatin by regulation of oxidative stress in a dextran sulfate sodium (DSS)-induced colitis model. Methods: An acute colitis mouse model was induced by oral administration of 5% DSS in the drinking water for 7 d. In the treated group, rosuvastatin (0.3 mg/kg per day) was administered orally before and after DSS administration for 21 d. On day 21, mice were sacrificed and the colons were removed for macroscopic examination, histology, and Western blot analysis. In the in vitro study, IEC-6 cells were stimulated with 50 ng/mL tumor necrosis factor (TNF)-α and then treated with or without rosuvastatin (2 μmol/L). The levels of reactive oxygen species (ROS), inflammatory mediators, and apoptotic markers were measured.

 

Title:
Blocking Virus Replication during Acute Murine Cytomegalovirus Infection Paradoxically Prolongs Antigen Presentation and Increases the CD8+ T Cell Response by Preventing Type I IFN–Dependent Depletion of Dendritic Cells 

Publication:
J Immunol 2017: doi.org/10.4049/jimmunol.1600478

Author(s):
Christopher P. Loo, Christopher M. Snyder and Ann B. Hill

Quansys Products Used:
Mouse Cytokine Screen

Abstract:

Increasing amounts of pathogen replication usually lead to a proportionate increase in size and effector differentiation of the CD8+ T cell response, which is attributed to increased Ag and inflammation. Using a murine CMV that is highly sensitive to the antiviral drug famciclovir to modulate virus replication, we found that increased virus replication drove increased effector CD8+ T cell differentiation, as expected. Paradoxically, however, increased virus replication dramatically decreased the size of the CD8+ T cell response to two immunodominant epitopes. The decreased response was due to type I IFN–dependent depletion of conventional dendritic cells and could be reproduced by specific depletion of dendritic cells from day 2 postinfection or by sterile induction of type I IFN. Increased virus replication and type I IFN specifically inhibited the response to two immunodominant epitopes that are known to be dependent on Ag cross-presented by DCs, but they did not inhibit the response to “inflationary” epitopes whose responses can be sustained by infected nonhematopoietic cells. Our results show that type I IFN can suppress CD8+ T cell responses to cross-presented Ag by depleting cross-presenting conventional dendritic cells.

 

Title:
Frontal Traumatic Brain Injury Increases Impulsive Decision Making in Rats: A Potential Role for the Inflammatory Cytokine Interleukin-12 

Publication:
Journal of Neurotrauma 2017: doi.org/10.1089/neu.2016.4813

Author(s):
Vonder Haar Cole, Martens Kris M., Riparip Lara-Kirstie, et al.

Quansys Products Used:
Multiplex ELISA

Abstract:

Traumatic brain injury (TBI) is associated with the development of numerous psychiatric diseases. Of particular concern for TBI patients is the impact of chronic impulsivity on daily functioning. Despite the scope of the human problem, little has been done to address impulsivity in animal models of brain injury. In the current study, we examined the effects of either a severe or a milder bilateral frontal controlled cortical impact injury on impulsivity using the Delay Discounting Task (DDT), in which preference for smaller-sooner over larger-later rewards is indicative of greater impulsive choice. Both milder and severe TBI caused a significant, chronic increase in impulsive decision making. Despite these pronounced changes in performance of the DDT, memory function, as assessed by the Morris Water Maze, was not impaired in more mildly injured rats and only transiently impacted in the severe TBI group. Whereas a significant lesion was only evident in severely injured rats, analysis of cytokine levels within the frontal cortex revealed a selective increase in interleukin (IL)-12 that was associated with the magnitude of the change in impulsive choice caused by both milder and severe TBI. These findings suggest that tissue loss alone cannot explain the increased impulsivity observed, and that inflammatory pathways mediated by IL-12 may be a contributing factor. The findings from this study highlight the sensitivity of sophisticated behavioral measures designed to assess neuropsychiatric dysfunction in the detection of TBI-induced cognitive impairments and their utility in identifying potential mechanistic pathways and therapeutic targets.

 

Title:
Comprehensive Profiling of Immune Responses in MARV Survivors Demonstrates Robust Th1-Skewing with Short Lived Neutralizing Antibody Responses

Publication:
Virology Division – U.S. Army Medical Research Institute of Infectious Diseases, 2017

Author(s):
Spencer W. Stonier, Andrew S. Herbert, Ana I. Kuehne, et al.

Quansys Products Used:
Q-Plex Chemiluminescent Assay, Q-View Imager and Q-View Software

Abstract:

The genera Marburgvirus and Ebolavirus comprise the family Filoviridae, which contains the etiological agents that cause Marburg virus disease and Ebola virus disease, respectively. Ebola virus (EBOV) recently caused an outbreak of truly unprecedented scale, spanning two years and infecting more than 28,000 individuals. Previously, the largest filovirus outbreaks had numbered in the tens to hundreds. While EBOV is responsible for the greatest number of human filovirus infections, Marburg virus (MARV), Sudan virus (SUDV), and Bundibugyo virus (BDBV) have all caused outbreaks that numbered over 100 cases twice, in the cases of MARV and SUDV. EBOV may garner much of the attention, but it is only one of several filoviruses that could potentially kindle outbreaks of massive scale. To date, there have been 11 incidences of MARV transmission to the human population. While many outbreaks have been of limited scale, afflicting fewer than 5 individuals per instance, two outbreaks alone account for 406 cases of MARV infections that had fatality rates of 83 and 90 (Bausch et al., 2006; Towner et al., 2006).

 

Title:
Immortalization of primary microglia: a new platform to study HIV regulation in the central nervous system