Monocyte gene expression distinguishes enhancing brain parenchymal cysticercal granulomas from tuberculomas

Abstract Background In patients with enhancing brain parenchymal lesions, parenchymal neurocysticercosis (pNCC) is often difficult to distinguish from tuberculoma, necessitating biopsy or empirical therapy. Materials and methods In a prospective study, peripheral blood monocytes were isolated from patients with definitive pNCC (n=39) and brain tuberculomas (n=20). Patients with tuberculomas were diagnosed by the presence of concurrent systemic tuberculosis (n=7), pathological or bacteriological confirmation (n=5), and resolution of typical brain lesions following a therapeutic trial of anti-tuberculous therapy (n=8). Expressions of 14 NCC associated monocyte genes were determined by qPCR and analyzed for diagnostic usefulness between the two groups. Results Expression of seven genes (TAX1BP1, RAP1A, PLCG2, TOR3A, GBP1P1, LRRFIP2 and FEZ2) was significantly higher in pNCC patients than in tuberculoma patients with TAX1BP1 and RAP1A expressions greater than 22- and 5-fold higher in pNCC patients. TAX1BP1 had the highest sensitivity of 66.7% at a specificity of 100% in discriminating pNCC from tuberculoma. A combination of TAX1BP1 and RAP1A increased the sensitivity to 84.6% and including GBP1P1 with TAX1BP1 and RAP1A further increased sensitivity to 87.2% while maintaining specificity of 100%. Conclusion Expression of a panel of genes in blood monocytes distinguishes pNCC from brain tuberculomas in patients with enhancing brain lesions.

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IL-4 down-regulates IL-2-, IL-3-, and GM-CSF-induced cytokine gene expression in peripheral blood monocytes

Annals of Hematology ◽

10.1007/bf01695035 ◽

1994 ◽

Vol 68 (6) ◽

pp. 293-298 ◽

Cited By ~ 5

Author(s):

F. H. M. Cluitmans ◽

B. H. J. Esendam ◽

J. E. Landegent ◽

R. Willemze ◽

J. H. F. Falkenburg

Keyword(s):

Gene Expression ◽

Peripheral Blood ◽

Cytokine Gene Expression ◽

Cytokine Gene ◽

Blood Monocytes ◽

Peripheral Blood Monocytes ◽

Gm Csf

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Microarray Analysis of Peripheral Blood Monocytes in Sickle Cell Anemia Patients with Cerebrovascular Stenosis.

Blood ◽

10.1182/blood.v104.11.3570.3570 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3570-3570

Author(s):

M. Catherine Driscoll ◽

Remi Adenika ◽

Ronald L. Nagel ◽

Eric P. Hoffman

Keyword(s):

Gene Expression ◽

Cell Signaling ◽

Differentially Expressed Genes ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Peripheral Blood ◽

Blood Monocytes ◽

Peripheral Blood Monocytes ◽

Lymphocyte Antigen ◽

Antigen Complex

Abstract Cerebrovascular disease (CVD) of both large and small cerebral vessels occurs in one-third of patients with sickle cell anemia (SCA) by age 20 years. Large vessel stenosis (LVS) occurs in ~10% of patients and is associated with overt stroke and/or (+) transcranial Doppler (TCD). Epistatic genetic modifiers are postulated to account for the significant phenotypic heterogeneity of SCA and likely contribute to CVD. Potential genetic modifers of CVD may be found in pathways for inflammation, adhesion, stress/immune reactions, angiogenesis, thrombosis, and oxidant generation. Peripheral blood monocytes are activated in SCA and contribute to inflammation and endothelial activation. The goal of this study is to determine if there is a difference in gene expression profiles of monocytes in patients with SCA and LVS, compared to SCA controls without CVD, and to normal African American (AA) controls. The study group consisted of 1) SCA patients with LVS [n = 6, (moyamoya = 3, no moyamoya =3)], 2) SCA patients without CVD and nornal TCD (n = 3), and 3) normal AA controls (n = 3). The 6 SCA-LVS patients were on chronic transfusion programs to maintain Hb S <30%. Monocytes were isolated by negative selection (RosetteSep Antibody) and total RNA extracted, converted to cRNA and hybridized to Affymetrix U133A GeneChip. Gene profiles were analyzed using dChip version 1.3 and gene lists were created for genes with a 2-fold or greater increase or decrease in expression with a Welch t-test p-values of 0.05 or less. Results: 1) SCA controls without CVD compared to AA controls revealed 50 differentially expressed genes (p<0.05), 16 with 2-fold or greater change. Differential gene expression was observed in pathways for angiogenesis (PD-ECGF, 5.1 fold, p = 0.025), cell signaling (lymphocyte antigen complex 6, 10.4 fold, p = 0.032, STAT1, 5.1 fold, p = 0.039), and inflammation (MARCO, 3.1 fold, p = 0.042). 2) SCA patients with LVS compared to SCA controls revealed 47 differentially expressed genes (p = <0.05) but only 6 genes with 2-fold or greater change. These included angiogenesis (PD-ECFG, -3.59 fold, p = 0.02), cell signaling (lymphocyte antigen complex 6, −4.61 fold, p = 0.02), adhesion (junction plakoglobin, −7.73 fold, p = 0.03), inflammation (LTA4H, 2.57 fold, p =0.009). These data suggest that patients with SCA and LVS overexpress leukotriene A4 hydrolase (LTA4H), an enzyme that catalyzes the final step in the leukotriene B4 (LTB4) pathway. LTB4 is a chemoattractant which triggers adhesion and aggregation of leukocytes to the endothelium. Five-lipoxygenase-activating protein (FLAP), a leukotriene pathway protein has recently been identified as a candidate gene for stroke and AMI risk in an Icelandic population. Also of interest, the SCA-LVS patients showed decreased expression of PD-ECFG and lymphocyte antigen complex 6, both genes being significantly overexpressed in SCA controls. Since the SCA-LVS patients are on chronic transfusion, underexpression could be due to the ameliorating effects of transfusion therapy. Validation studies of these findings are currently underway.

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Pluripotency Gene Expression and Growth Control in Cultures of Peripheral Blood Monocytes during Their Conversion into Programmable Cells of Monocytic Origin (PCMO): Evidence for a Regulatory Role of Autocrine Activin and TGF-β

PLoS ONE ◽

10.1371/journal.pone.0118097 ◽

2015 ◽

Vol 10 (2) ◽

pp. e0118097 ◽

Cited By ~ 6

Author(s):

Hendrik Ungefroren ◽

Ayman Hyder ◽

Hebke Hinz ◽

Stephanie Groth ◽

Hans Lange ◽

...

Keyword(s):

Gene Expression ◽

Peripheral Blood ◽

Growth Control ◽

Regulatory Role ◽

Blood Monocytes ◽

Peripheral Blood Monocytes ◽

Pluripotency Gene

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Hepatocyte growth factor–stimulated invasiveness of monocytes

Blood ◽

10.1182/blood.v95.12.3964 ◽

2000 ◽

Vol 95 (12) ◽

pp. 3964-3969 ◽

Cited By ~ 46

Author(s):

Mario Beilmann ◽

George F. Vande Woude ◽

Hans-Peter Dienes ◽

Peter Schirmacher

Keyword(s):

Gene Expression ◽

Growth Factor ◽

Hepatocyte Growth Factor ◽

Gene Expression Profile ◽

Expression Profile ◽

Peripheral Blood ◽

Blood Monocytes ◽

Peripheral Blood Monocytes ◽

Hepatocyte Growth ◽

Stimulation Of

Abstract Hepatocyte growth factor (HGF) is a pluripotent cytokine with mitogenic, motogenic, and morphogenic activity for mainly epithelial and endothelial target cells. We previously demonstrated that the specific HGF receptor, MET, is induced in stimulated peripheral blood monocytes. In this study, we analyzed the functional consequences of MET activation in primary cultures of peripheral blood monocytes from healthy donors. After stimulation of MET-expressing monocytes with recombinant HGF, the gene-expression profile of peripheral blood mononuclear cells and monocytes was significantly modulated, especially with regard to genes involved in cell movement. After stimulation of primary cultured monocytes with HGF, invasion assays showed a significantly increased matrigel invasion rate that was completely abolished by neutralizing antibodies to HGF. The HGF-activated invasiveness and the altered gene-expression profile suggest a proinflammatory role for HGF stimulation of monocytes and support the hypothesis that the HGF/MET signaling system plays an important part in the activation of the nonspecific cellular inflammatory response.

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