scholarly journals Whole-Genome mRNA Gene Expression Differs Between Patients With and Without Delirium

2018 ◽  
Vol 31 (4) ◽  
pp. 203-210 ◽  
Author(s):  
Katrina Kalantar ◽  
Sara C. LaHue ◽  
Joseph L. DeRisi ◽  
Hannah A. Sample ◽  
Caitlin A. Contag ◽  
...  
Keyword(s):  
Gene Expression ◽  
Messenger Rna ◽  
Transcriptional Profiling ◽  
Significant Inhibition ◽  
Unknown Etiology ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Mrna Gene ◽  
Transcription Regulators ◽  
Significant Activation

Objective: To identify differences in gene expression between patients with in-hospital delirium from a known etiology (urinary tract infection [UTI]) and patients with delirium from an unknown etiology, as well as from nondelirious patients. Methods: Thirty patients with delirium (8 with UTI) and 21 nondelirious patients (11 with UTI) were included in this prospective case–control study. Transcriptomic profiles from messenger RNA sequencing of peripheral blood were analyzed for gene expression and disease-specific pathway enrichment patterns, correcting for systemic inflammatory response syndrome. Genes and pathways with significant differential activity based on Fisher exact test ( P < .05, |Z score| >2) are reported. Results: Patients with delirium with UTI, compared to patients with delirium without UTI, exhibited significant activation of interferon signaling, upstream cytokines, and transcription regulators, as well as significant inhibition of actin cytoskeleton, integrin, paxillin, glioma invasiveness signaling, and upstream growth factors. All patients with delirium, compared to nondelirious patients, had significant complement system activation. Among patients with delirium without UTI, compared to nondelirious patients without UTI, there was significant activation of elF4 and p7056 K signaling. Conclusions: Differences exist in gene expression between delirious patients due to UTI presence, as well as due to the presence of delirium alone. Transcriptional profiling may help develop etiology-specific biomarkers for patients with delirium.

Mapping cis-acting regulatory variation in recombinant congenic strains

2006 ◽  
Vol 25 (2) ◽  
pp. 294-302 ◽  
Author(s):  
Peter D. Lee ◽  
Bing Ge ◽  
Celia M. T. Greenwood ◽  
Donna Sinnett ◽  
Yannick Fortin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Fisher Exact Test ◽  
Donor Strain ◽  
Exact Test ◽  
Expression Levels ◽  
Cis Acting ◽  
Congenic Strains ◽  
Recombinant Congenic Strains ◽  
Genetic Context

We present an integrated approach for the enriched detection of genes subject to cis-acting variation in the mouse genome. Gene expression profiling was performed with lung tissue from a panel of recombinant congenic strains (RCS) derived from A/J and C57BL/6J inbred mouse strains. A multiple-regression model measuring the association between gene expression level, donor strain of origin (DSO), and predominant strain background identified over 1,500 genes ( P < 0.05) whose expression profiles differed according to the DSO. This model also identified over 1,200 genes whose expression showed dependence on background ( P < 0.05), indicating the influence of background genetic context on transcription levels. Sequences obtained from 1-kb segments of 3′-untranslated regions identified single nucleotide polymorphisms in 64% of genes whose expression levels correlated with DSO status, compared with 29% of genes that displayed no association ( P < 0.01, Fisher exact test). Allelic imbalance was identified in 50% of genes positive for expression-DSO association, compared with 22% of negative genes ( P < 0.05, Fisher exact test). Together, these results demonstrate the utility of RCS mice for identifying the roles of proximal genetic determinants and background genetic context in determining gene expression levels. We propose the use of this integrated experimental approach in multiple tissues from this and other RCS panels as a means for genome-wide cataloging of genetic regulatory mechanisms in laboratory strains of mice.

scholarly journals Interferon-gamma gene expression in unstimulated bone marrow mononuclear cells predicts a good response to cyclosporine therapy in aplastic anemia

Blood ◽  
1992 ◽  
Vol 79 (10) ◽  
pp. 2532-2535 ◽  
Author(s):  
S Nakao ◽  
M Yamaguchi ◽  
S Shiobara ◽  
T Yokoi ◽  
T Miyawaki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Aplastic Anemia ◽  
Interferon Gamma ◽  
Messenger Rna ◽  
Mononuclear Cells ◽  
Bone Marrow Mononuclear Cells ◽  
Ifn Gamma ◽  
Exact Test ◽  
Transfusion Independence

Cyclosporine (CyA) therapy has been shown to be effective in some patients with aplastic anemia. In an attempt to characterize aplastic patients likely to benefit from CyA therapy, we examined bone marrow mononuclear cells (BMMC) obtained before therapy from 23 patients with aplastic anemia, who were treated with CyA alone. Expression of four myelosuppressive cytokines, including tumor necrosis factor (TNF), lymphotoxin, macrophage inflammatory protein-1 alpha (MIP-1 alpha), and interferon-gamma (IFN-gamma) was examined using polymerase chain reaction (PCR)-assisted messenger RNA (mRNA) amplification. mRNA for TNF, lymphotoxin, and MIP-1 alpha was readily detectable at variable levels in BMMC from normal and transfused controls as well as in BMMC from aplastic patients. In contrast, IFN-gamma mRNA was only demonstrable in BMMC from some patients with aplastic anemia, irrespective of a history of transfusions. Of 13 patients who responded to CyA therapy and achieved transfusion-independence, IFN-gamma mRNA was detected in 12 patients, whereas the mRNA was only detectable in 3 of 10 patients refractory to CyA therapy (P = .003, Fisher's exact test). Follow-up examination of BMMC obtained from seven CyA-responding patients after hematologic remission showed disappearance of IFN-gamma mRNA in four patients. These results suggest that detection of IFN- gamma gene expression in pretreatment BMMC from aplastic patients using PCR may be helpful in predicting a good response to CyA therapy.

Gene expression signatures in MLL-rearranged T-lineage and B-precursor acute leukemias: dominance of HOX dysregulation

Blood ◽  
2003 ◽  
Vol 102 (1) ◽  
pp. 262-268 ◽  
Author(s):  
Adolfo A. Ferrando ◽  
Scott A. Armstrong ◽  
Donna S. Neuberg ◽  
Stephen E. Sallan ◽  
Lewis B. Silverman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hox Genes ◽  
Wilcoxon Test ◽  
Leukemic Cells ◽  
Fisher Exact Test ◽  
Leukemic Transformation ◽  
Acute Leukemias ◽  
Exact Test ◽  
Expression Of Genes ◽  
Thymocyte Differentiation

Abstract Rearrangements of the MLL locus, located on human chromosome 11q23, are frequent in both infant and therapy-related leukemias. Gene expression analysis of MLL-rearranged B-precursor acute lymphoblastic leukemias (MLL B-ALLs) has identified these cases as a unique subtype of leukemia, characterized by the expression of genes associated with both lymphoid and myeloid hematopoietic lineages. Here we show that MLL fusions also generate a distinct genetic subtype of T-lineage ALL (MLL T-ALL), in which leukemic cells are characterized by an early arrest in thymocyte differentiation, with suggestive evidence of commitment to the γδ lineage. Interestingly, multiple genes linked to cell proliferation (eg, PCNA, MYC, CDK2, and POLA) were down-regulated in MLL-fusion samples, relative to those transformed by other T-ALL oncogenes (P &lt; .000 001, Fisher exact test). Overall, MLL T-ALL cases consistently demonstrated increased levels of expression of a subset of major HOX genes—HOXA9, HOXA10, and HOXC6—and the MEIS1 HOX coregulator (P &lt; .008, one-sided Wilcoxon test), a pattern of gene expression that was reiterated in MLL B-ALLs. However, expression of myeloid lineage genes, previously reported in MLL B-ALLs, was not identified in T-lineage cases with this abnormality, suggesting that myeloid gene dysregulation is dispensable in leukemic transformation mediated by MLL fusion proteins. Our findings implicate dysregulation of HOX gene family members as a dominant mechanism of leukemic transformation induced by chimeric MLL oncogenes. (Blood. 2003;102:262-268)

Tenascin-C Is Highly Expressed in T-Cell Non-Hodgkin Lymphomas and Represents an Attractive Target for Radioimmunotherapy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4141-4141 ◽  
Author(s):  
Giuseppe Gritti ◽  
Andrea Gianatti ◽  
Fiorella Petronzelli ◽  
Cristina Boschini ◽  
Riccardo Rossi ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Poor Prognosis ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Fisher Exact Test ◽  
Chi Square ◽  
Exact Test ◽  
Tenascin C ◽  
Normal Tissues

Abstract Introduction: Tenascins are a family of large glycoproteins present in extracellular matrix, overexpressed in tumors compared to healthy tissues. Tenatumomab (ST2146) is an anti tenascin-C monoclonal antibody that is currently under development for radio immunotherapy (RIT) in tenascin-C expressing cancer. T-cell non-Hodgkin lymphomas (T-NHL) are a heterogeneous and rare group of poor prognosis malignancies lacking of standard treatments. Aim of the study was to evaluate the expression of tenascin-C in a cohort of T-NHL. Material and Methods: Under an IRB-approved protocol, 100 patients with a diagnosis of T-NHL in charge at the Hematology Unit of "Papa Giovanni XXII" Hospital were included in the study. Paraffin-embedded tumor samples were investigated using standard immunohistochemistry (IHC) for tenascin-C expression using tenatumomab antibody. Slides were assessed by two independent investigators. Staining was scored using the four different levels "no staining", "weak", "moderate" and "strong" (0-3). A grading system was used to express the proportion of involved areas in each case, as follows: 0 (0% to 25%), 1 (26% to 50%), 2 (51% to 75%), 3 (76% to 100%). Pattern of expression (stromal, vascular and/or cytoplasmic) was as well recorded. Tenascin C gene expression data were extracted from publicly available datasets. Association among variables was assessed with Chi square or Fisher exact test. Results:Of the 100 patients evaluated, 75 cases were peripheral T-NHL (PTCL) and 25 cutaneous T-NHL (CTCL). Specific diagnosis was, anaplastic large cell lymphoma (ALCL) ALK negative (n=21) or positive (n=19), PTCL-not otherwise specified (NOS, n=20), mycosis fungoides (n=13), angioimmunoblastic T-cell lymphoma (AITL, n=9), CD30+ primary cutaneous T-NHL (n=6) and other subtypes (n=12). Tenatumomab revealed the expression of tenascin-C in all the patients, with a staining that was weak, moderate and strong in 21, 51 and 28 of the cases. There was no significant different distribution among histologies (P=0.334). A high (>50%, grade 2-3) proportion of involved areas in pathologic samples were shown in half of the patients and this proportion was higher in ALCL ALK- (81%), AITL (78%) and ALCL ALK+ (58%) while was lower for PTCL NOS (30%) and CTCL (24%) (P=0.0019). A stromal pattern of expression was present in all the cases, vasculature was stained in 47 patients while in 21 tenascin-C was as well cytoplasmic. Vascular pattern was revealed in 56% of PTCL and 20% of CTCL (P=0.0018). To further evaluate the presence of tenascin C in T-NHL, gene expression datasets from published reports were retrieved and expression values of tenascin-C gene were extracted. Significant overexpression was present in T-NHL compared to normal tissues in both of the two considered datasets (Piccaluga et al., 2007 and Iqbal et al., 2010). Conclusions: Tenatumomab revealedthat tenascin-C is uniformly present in T-NHL with a high proportion of cases showing a strong and diffuse expression. Thus, tenascin-C represent an attractive target for RIT in this category of poor prognosis rare diseases. Disclosures Petronzelli: Sigma Tau S.p.A: Employment.

scholarly journals Proinflammatory Effects of Diesel Exhaust Nanoparticles on Scleroderma Skin Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
A. Mastrofrancesco ◽  
M. Alfè ◽  
E. Rosato ◽  
V. Gargiulo ◽  
C. Beatrice ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Cytokine Gene Expression ◽  
Unknown Etiology ◽  
Dependent Manner ◽  
Collagen Types ◽  
Normal Cells ◽  
Complex Disorders ◽  
Mrna Gene

Autoimmune diseases are complex disorders of unknown etiology thought to result from interactions between genetic and environmental factors. We aimed to verify whether environmental pollution from diesel engine exhaust nanoparticulate (DEP) of actually operating vehicles could play a role in the development of a rare immune-mediated disease, systemic sclerosis (SSc), in which the pathogenetic role of environment has been highlighted. The effects of carbon-based nanoparticulate collected at the exhaust of newer (Euro 5) and older (Euro 4) diesel engines on SSc skin keratinocytes and fibroblasts were evaluatedin vitroby assessing the mRNA expression of inflammatory cytokines (IL-1α, IL-6, IL-8, and TNF-α) and fibroblast chemical mediators (metalloproteases 2, 3, 7, 9, and 12; collagen types I and III; VEGF). DEP was shown to stimulate cytokine gene expression at a higher extent in SSc keratinocytes versus normal cells. Moreover, the mRNA gene expression of all MMPs, collagen types, and VEGF genes was significantly higher in untreated SSc fibroblasts versus controls. Euro 5 particle exposure increased the mRNA expression of MMP-2, -7, and -9 in SSc fibroblasts in a dose dependent manner and only at the highest concentration in normal cells. We suggest that environmental DEP could trigger the development of SSc acting on genetically hyperreactive cell systems.

scholarly journals A.04 Anatomic variation of the Circle of Willis in perinatal stroke

2016 ◽  
Vol 43 (S2) ◽  
pp. S8-S8
Author(s):  
PN de Jesus ◽  
A Mineyko ◽  
A Kirton ◽  
S Yu
Keyword(s):  
Anatomic Variation ◽  
Circle Of Willis ◽  
Posterior Circulation ◽  
Unknown Etiology ◽  
Fisher Exact Test ◽  
Lesion Volume ◽  
Anterior Circulation ◽  
Perinatal Stroke ◽  
Exact Test ◽  
Stroke Type

Background: Perinatal stroke is a common disorder in neonates with unknown etiology. Previous studies have linked anatomic variations in the Circle of Willis to adult stroke. This study aimed to understand the potential relationship between circle anatomy and common forms of perinatal stroke: NAIS, APPIS, and PVI. Methods: 94 subjects (62 NAIS/APPIS, and 32 PVI) were identified from the Alberta Perinatal Stroke Project. Inclusion criteria were: MRI-confirmed perinatal stroke, 3D-TOF MRA, and absence of other disorders. Images were classified as complete, incomplete posterior circulation, incomplete anterior circulation, and incomplete anterior and posterior circulation. Fisher Exact Test compared completeness against stroke type and segment absence ipsilateral to stroke. Mann-Whitney U compared completeness and lesion volume. Results: Completeness was more common in PVI than NAIS/APPIS (p=0.500) and in healthy controls than total stroke population (p=0.251). Ipsilesional absent segments were more frequent in NAIS/APPIS (p= 0.270). NAIS/APPIS patients with complete CoW had larger median lesion volume was compared to those with incomplete circles (p=0.484), with contralateral absence (p=0.943), and with ipsilateral absence (p=1.00). The opposite was found in PVI patients for all lesion volume comparisons (p=0.321, 0.362, 0.739 respectively). Conclusions: Circle anatomy is highly variable in perinatal stroke. Absence of segments is not associated with stroke type, lesion side, and lesion volume.

scholarly journals 1195. Influence of Histoplasma capsulatum Infection on Endothelin-1 mRNA Gene Expression in Bone Marrow Derived Macrophages

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S619-S620
Author(s):  
Eloho Ajayi ◽  
George S Deepe ◽  
William R Buesing
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Messenger Rna ◽  
Histoplasma Capsulatum ◽  
Time Points ◽  
Endothelin 1 ◽  
Endothelin System ◽  
Mrna Gene ◽  
Mrna Gene Expression

Abstract Background Endothelin-1 (ET-1) is increasingly recognized as an immune modulator; it exerts a pro-inflammatory effect by increasing the release of cytokines like interferon gamma. ET-1 is secreted by a variety of cells such as macrophages, neurons and endothelial cells. Activation of the endothelin system has been implicated in the pathogenesis of sepsis caused by bacteria, viruses and even parasites. However, there are no published studies that have explored the role of ET-1 in Histoplasma capsulatum infection. Studying the role of ET-1 in histoplasmosis is important because understanding its role in the host defense mechanism may serve as the foundation for future discovery of novel therapeutic options. Methods Bone marrow cells were isolated from mice and set up for tissue culture. Bone marrow derived macrophages (BMDM) were harvested after 5-7 days of incubation, and infected with varying ratios (0.5,1 and 5) of yeasts to macrophages. RNA was extracted from the BMDM after 3, 6, 24 and 48 hours of infection. For comparison, RNA was also extracted from uninfected BMDM at the same time points. Real-time PCR (polymerase chain reaction) was performed on complementary DNA. ET-1 (Edn1) messenger RNA (mRNA) gene expression was quantified relative to the expression of the house keeping /endogenous control gene that encodes for beta-2 microglobulin (B2m). Results In BMDM infected with H. capsulatum there was upregulation of Edn1 after 3, 6 and 24 hours of infection. During this same time points, the expression of ET-1 mRNA in the uninfected BMDM remained constant. Expression of Edn1 was highest in the BMDM infected with 5x H. capsulatum after 3 and 6 hours of infection. After 24 hours, the expression of ET-1 mRNA decreased markedly in all concentrations of H. capsulatum. At 48 hours post-infection the Edn1 was downregulated in the 0.5,1 and 5-fold quantities of H. capsulatum across all time the time intervals. Figure 1 Conclusion Results from this study indicate that H. capsulatum infection induced an upregulation of the Edn-1 in BMDM. This may correlate with an increase in levels of ET-1 production by the BMDM in the face of H. capsulatum infection. These results provide a platform in which to examine the influence of ET-1 on the host response to this fungus. Disclosures All Authors: No reported disclosures

scholarly journals Interferon-gamma gene expression in unstimulated bone marrow mononuclear cells predicts a good response to cyclosporine therapy in aplastic anemia

Blood ◽  
1992 ◽  
Vol 79 (10) ◽  
pp. 2532-2535 ◽  
Author(s):  
S Nakao ◽  
M Yamaguchi ◽  
S Shiobara ◽  
T Yokoi ◽  
T Miyawaki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Aplastic Anemia ◽  
Interferon Gamma ◽  
Messenger Rna ◽  
Mononuclear Cells ◽  
Bone Marrow Mononuclear Cells ◽  
Ifn Gamma ◽  
Exact Test ◽  
Transfusion Independence

Abstract Cyclosporine (CyA) therapy has been shown to be effective in some patients with aplastic anemia. In an attempt to characterize aplastic patients likely to benefit from CyA therapy, we examined bone marrow mononuclear cells (BMMC) obtained before therapy from 23 patients with aplastic anemia, who were treated with CyA alone. Expression of four myelosuppressive cytokines, including tumor necrosis factor (TNF), lymphotoxin, macrophage inflammatory protein-1 alpha (MIP-1 alpha), and interferon-gamma (IFN-gamma) was examined using polymerase chain reaction (PCR)-assisted messenger RNA (mRNA) amplification. mRNA for TNF, lymphotoxin, and MIP-1 alpha was readily detectable at variable levels in BMMC from normal and transfused controls as well as in BMMC from aplastic patients. In contrast, IFN-gamma mRNA was only demonstrable in BMMC from some patients with aplastic anemia, irrespective of a history of transfusions. Of 13 patients who responded to CyA therapy and achieved transfusion-independence, IFN-gamma mRNA was detected in 12 patients, whereas the mRNA was only detectable in 3 of 10 patients refractory to CyA therapy (P = .003, Fisher's exact test). Follow-up examination of BMMC obtained from seven CyA-responding patients after hematologic remission showed disappearance of IFN-gamma mRNA in four patients. These results suggest that detection of IFN- gamma gene expression in pretreatment BMMC from aplastic patients using PCR may be helpful in predicting a good response to CyA therapy.

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