scholarly journals Expression Analysis of Cytokine and Chemokine Genes during the Natural Course of Murine Experimental Autoimmune Uveoretinitis

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Noriyasu Hashida ◽  
Nobuyuki Ohguro ◽  
Kohji Nishida

C57BL/6 mice were immunized with human interphotoreceptor retinoid-binding protein peptides to induce experimental autoimmune uveoretinitis (EAU). From the day of immunization to 30 days later, RNA was isolated daily from the mouse eyes. Dynamic changes in gene expression during the pathogenesis of EAU were analyzed by TaqMan gene expression assay that contained most chemokines/cytokines and their receptors, and signal transducer and activator of transcription (STAT) family genes, using beta-actin as the endogenous control. Gene clusters based on their expression profiles were analyzed to determine the candidate genes for the pathogenesis of inflammation. Hierarchical cluster analysis showed gene expression during EAU development in seven clustering patterns. Hierarchical cluster analysis also identified four distinct phases in daily expression: entrance, acceleration, deceleration, and remission. Gene expression changes in the EAU active phase showed synergetic upregulation of Th1-type genes (IFN-gamma and CXCL10/IP-10) with elevated Th2-type genes (CCL17/TARC and IL-5). Sequential expression changes of STAT1, STAT6, and STAT3 genes represented the dynamic changes of Th1, Th2, and Th17-type inflammatory genes, respectively. The expression pattern of STAT1 was representative of many gene movements. Our results suggested that coordinated action of Th1, Th2, and Th17 genes and STAT family genes are involved in EAU development and resolution.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3174-3174 ◽  
Author(s):  
Evdoxia Hatjiharissi ◽  
Constantine S. Mitsiades ◽  
Ciccarelli T. Bryan ◽  
Xu Lian ◽  
Cao Yang ◽  
...  

Abstract Waldenstrom’s Macroglobulinemia (WM) is an incurable B-cell malignancy characterized by bone marrow (BM) infiltration with a spectrum of clonally related cells, including small lymphocytes and lymphoplasmacytic cells (CD19+) as well as mature plasma cells (CD138+). The molecular pathogenesis of the disease remains to be defined. We therefore analyzed the gene expression profiles of CD19+ and CD138+ BM mononuclear cells from 30 untreated patients with WM and compared their gene expression profile to their normal counterparts from 10 healthy donors using Affymetrix microarrays (U133 plus 2.0). Since the microenvironment plays an important role in the pathogenesis of WM, we also profiled and compared gene expression profiling for CD19 and CD138 depleted BM mononuclear cells from the same patients and healthy donors. Gene expression analysis was performed using dChip software. Unsupervised hierarchical cluster analysis demonstrated distinct gene expression patterns between WM cells versus their normal counterparts. In supervised hierarchical cluster analysis selecting for genes with > 2 fold change in expression and a False discovery Rate (FDR) < 2%, a set of 1171, 582 and 360 genes were found to be differentially expressed between WM patient and healthy donor CD19+, CD138+, as well as CD19/CD138 depleted (microenvironmental) cells, respectively. Among the most significantly over-expressed genes in the CD19+ compartment in WM patients were: BCL2, TNFRSF13B, TNFRSF17, IGLL1, CCR2, CLLU1, whilst the AP1 family genes JUND and FOSB were among the most significantly down-regulated genes in both CD19+ and CD138+ cells in WM patients. Other interesting transcripts which were over-expressed in CD138+ cells from WM patients included those from genes involved in transcription regulation (ZKSCAN1, ZMYM1, ZNF189, ZNF19, and ZNF559) and interferon response (IFI16 and IFIH1). Of considerable interest was our observation that microenvironmental cells in WM patients demonstrated an overactive transcriptional profile composed of genes which are associated with immune and inflammatory responses including the Toll like receptors (TLR 1,5,7,8), interferon and cytokines (IFI16, IFNAR1, IL-10R, IL-8R), genes encoding extracellular matrix components (Fibronectin and Hepatocyte Growth Factor) as well as genes involved in apoptotic signaling (TNFSF10, TRAF4). These studies provide the first comprehensive molecular characterization of WM, dissecting the molecular features of the two immunophenotypically distinct populations of malignant cells, and providing for the first time evidence for a distinct molecular profile in BM microenviromental cells.





Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1547-1547
Author(s):  
Fenghuang Zhan ◽  
Yongsheng Huang ◽  
Rudy Van Hemert ◽  
Owen Stephens ◽  
Bart Barlogie ◽  
...  

Abstract Background: We have previously shown that the GEP signatures of whole bone marrow biopsies from patients with MM can be distinguished from those of normal healthy subjects. What is not clear is whether the GEP of myeloma Bx samples returns to normal in clinical remission following tandem stem cell transplantation. Patients and Methods: Samples included random Bx from 85 newly diagnosed MM patients treated on Total Therapy 2 protocol; 22 also had Bx in remission and 19 at relapse; in addition, Bx were available from 8 subjects with MGUS and 12 normal donors. Labeled cRNA was applied to Affymetrix U133Plus2 microarrays. Significant analysis of microarray (SAM) was performed to identify remission-related genes by comparing normal cases with remission cases. Unsupervised hierarchical cluster analysis was employed on Log2 transformed GEP intensity values of remission-related gene identified with SAM using a false discovery rate of 1%. Results: Altogether 998 genes were significantly differentially expressed in a comparison of normal and remission samples. Of these, 31 (3%) were higher and 967 (97%) lower in remission samples compared to normal donors. Two-dimensional hierarchical cluster analysis using the 998 genes and 22 remission and 12 normal donor samples provided visual evidence of 2 separate remission signatures. A single sample acquired what appeared to be a completely normal signature with 8 of 22 cases having a normal-like signature and 12 of the 22 cases having a distinct non-normal signature. Two-dimensional hierarchical clustering with remission-related genes using whole biopsies from 85 newly diagnosed MM, 8 MGUS, 22 remissions, and 19 relapses produced 2 major branches: one contained 50 MM (59%), 5 MGUS (63%), 10 remissions (45%), and 4 relapses (21%) with the second branch containing 35 MM (41%), 3 MGUS (37%), 12 remissions (55 %), and 15 relapses (79%). All 12 of the non-normal, while none of the 10 normal-like remissions, clustered in the group containing the majority of relapse cases (p=0.002). A comparison of 16 clinical variables amongst the newly diagnosed cases revealed that the 35 clustering with the non-normal remission cases were significantly associated with higher levels of B2M (P = 0.001), creatinine (P = 0.0056) and LDH (P = 0.024); higher incidence of abnormal (P = .0075) and a lower incidence of hyperdiploid karyotypes (P = 0.0004); higher levels of FISH-1q21 amplification (P = 0.04) and FISH-13 deletion (P = 0.04, 80% cutoff); lower HGB (P = 0.0058), and fewer MRI-defined focal lesions (P = 0.03). There was a strong trend for the presence of high-risk features at diagnosis among the 12 non-normal remission samples compared to the 10 normal-like samples. Of the 10 cases with the normal-like remission signature, 8 were on the thalidomide arm of the trial but only 4 of 12 patients with the non-normal remission signature were on the thalidomide arm (P=0.029). Conclusion: Despite -obtaining a clinical remission, the gene expression pattern within the marrow of myeloma patients does not return to normal in a substantial subset of patients.



2018 ◽  
Vol 55 (6) ◽  
pp. 821-837 ◽  
Author(s):  
Mun Keong Kok ◽  
James K. Chambers ◽  
Siew Mei Ong ◽  
Hiroyuki Nakayama ◽  
Kazuyuki Uchida

The diagnosis of cutaneous epithelial tumors (CETs) in dogs is based on predominant histological differentiation patterns. However, the expression of a broad panel of antigens has not been comprehensively examined with immunohistochemistry. The present study aims to establish a comprehensive expression profile and identify useful diagnostic markers for each CET type. Cytokeratin (CK), stem cell, and other associated markers were immunohistochemically examined in 110 canine CETs. Among these, CK16 was useful for differentiating between basal and squamous cell carcinomas. Acantholytic squamous cell carcinomas were positive for CK8, CK18, and CK19, suggesting their close association with the apocrine duct. Unlike their benign counterparts, sebaceous carcinomas coexpressed CK5/6 and adipophilin. Smooth muscle actin (SMA) and p63 immunostaining were useful for accurately distinguishing between glandular and ductal differentiation in apocrine tumors. A case of apocrine carcinoma and malignant myoepithelioma was identified using anti-SMA antibodies. Stem cell expression profiles (CK8, CK15, CK19, and CD34) of hair follicle tumors were discrete and indicative of their anatomic origins. The effectiveness of immunohistochemistry for tumor diagnosis was further confirmed by hierarchical cluster analysis, through which selected markers were able to sort CETs into specific groups: CK5/6, CK8, CK14, CK16, CK18, CK19, p63, adipophilin, and SMA sorted tumors of epidermal, apocrine, or sebaceous origin; while CK8, CK14, CK15, CK16, CK19, CD34, and p63 sorted hair follicle tumors in agreement with their histological differentiation. In conclusion, the present study provides comprehensive immunohistochemical information, which could complement histomorphological features for the future classification of canine CETs.



2011 ◽  
Vol 29 (6) ◽  
pp. 549-553
Author(s):  
Jian JIANG ◽  
Jun YANG ◽  
Fangfang HUANG ◽  
Shiqiang XU ◽  
Xiaoqing WANG ◽  
...  


Author(s):  
Milan Radojicic ◽  
Aleksandar Djokovic ◽  
Nikola Cvetkovic

Unpredictable and uncontrollable situations have happened throughout history. Inevitably, such situations have an impact on various spheres of life. The coronavirus disease 2019 has affected many of them, including sports. The ban on social gatherings has caused the cancellation of many sports competitions. This paper proposes a methodology based on hierarchical cluster analysis (HCA) that can be applied when a need occurs to end an interrupted tournament and the conditions for playing the remaining matches are far from ideal. The proposed methodology is based on how to conclude the season for Serie A, a top-division football league in Italy. The analysis showed that it is reasonable to play 14 instead of the 124 remaining matches of the 2019–2020 season to conclude the championship. The proposed methodology was tested on the past 10 seasons of the Serie A, and its effectiveness was confirmed. This novel approach can be used in any other sport where round-robin tournaments exist.







2010 ◽  
Vol 41 (2) ◽  
pp. 126-133 ◽  
Author(s):  
N. Kalamaras ◽  
H. Michalopoulou ◽  
H. R. Byun

In this study a method proposed by Byun & Wilhite, which estimates drought severity and duration using daily precipitation values, is applied to data from stations at different locations in Greece. Subsequently, a series of indices is calculated to facilitate the detection of drought events at these sites. The results provide insight into the trend of drought severity in the region. In addition, the seasonal distribution of days with moderate and severe drought is examined. Finally, the Hierarchical Cluster Analysis method is used to identify sites with similar drought features.



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