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Significant Overexpression (significant + overexpression)
Selected AbstractsVascular adhesion protein-1 (VAP-1) is overexpressed in psoriatic patientsJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 1 2007A Madej Abstract Background, Vascular adhesion protein (VAP)-1 is an adhesion molecule with an enzymatic activity that partakes in the migration process of lymphocytes. Objectives, The aim of this study was to investigate the expression of VAP-1 in the skin and serum of psoriatic patients. Material and methods, Seventy-one patients suffering from psoriasis aged between 23 and 89 years were included in the study. The mean psoriasis severity assessed according to the psoriasis area and severity index was 14.2 ± 9.6 points. The soluble VAP-1 serum concentration was evaluated by ELISA and VAP-1 expression in the skin (nine patients) immunohistochemically. Results, The serum concentration of soluble VAP-1 was significantly higher in psoriatic patients than in healthy controls (403.4 ± 130.8 ng/mL vs. 246.4 ± 68.0 ng/mL; P < 0.0001). No significant relationships were found between sVAP-1 concentration and studied clinical parameters, except the presence of pruritus. Mean number of VAP-1 positive vessels in psoriatic skin, both lesional (19.8 ± 1.4) and non-lesional (9.4 ± 1.4), was significantly higher than in healthy skin (5.4 ± 1.5; P < 0.005). Lesional psoriatic skin demonstrated significantly more VAP-1 positive vessels than non-lesional skin (P < 0.01). Conclusions, Significant overexpression of VAP-1 in both lesional and non-lesional psoriatic skin and higher serum level of soluble VAP-1 in psoriatic patients may indicate the role of VAP-1 in chronic inflammation occurring in psoriasis. However, because of lack of correlation between soluble VAP-1 serum levels and psoriasis severity this hypothesis needs further investigation. [source] Multiple P450 genes overexpressed in deltamethrin-resistant strains of Helicoverpa armigeraPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 8 2010Alexandra Brun-Barale Abstract BACKGROUND: Resistance to the pyrethroid insecticide deltamethrin has been a growing problem in the management of Helicoverpa armigera (Hübner) pest populations in West Africa. Detoxification by P450 enzymes appears to be a major mechanism of resistance, but the genes responsible for resistance are unknown. RESULTS: First, it was shown that deltamethrin resistance in strains from Burkina Faso (Kaya) and from Spain (Seville) were suppressible by piperonyl butoxide and by trichlorophenyl propynyl ether, thus indicating a major role of P450 enzyme(s) in resistance. The larval expression of 21 CYP genes encoding P450 enzymes from six CYP families were then compared by quantitative RT-PCR. Five genes, CYP4L5, CYP4L11, CYP6AE11, CYP332A1 and CYP9A14, were significantly overexpressed in the Kaya and Seville strains when compared with Heliar, a susceptible strain. Significant overexpression of multiple CYP genes (CYP4M6, CYP4M7, CYP6AE11, CYP9A12, CYP332A1 and CYP337B1) was also found in six field strains with different levels of resistance from Benin, Burkina Faso and Mali. CONCLUSION: Although functional or genetic evidence for the role of these P450s in resistance remains to be formally established, results suggest that multiple P450 enzymes contribute to deltamethrin resistance. This study is a first step towards the development of molecular tools for the detection of P450-based resistance in H. armigera. Copyright © 2010 Society of Chemical Industry [source] Expression of the Multidrug Transporter P-glycoprotein in Brain Capillary Endothelial Cells and Brain Parenchyma of Amygdala-kindled RatsEPILEPSIA, Issue 7 2002Ulrike Seegers Summary: ,Purpose: Based on data from brain biopsy samples of patients with pharmacoresistant partial epilepsy, overexpression of the multidrug transporter P-glycoprotein (PGP) in brain capillary endothelium has recently been proposed as a potential mechanism of resistance to antiepileptic drugs (AEDs). We examined whether PGP is overexpressed in brain regions of amygdala-kindled rats, a widely used model of temporal lobe epilepsy (TLE), which is often resistant to AEDs. Methods: Rats were kindled by stimulation of the basolateral amygdala (BLA); electrode-implanted but nonkindled rats and naive (not implanted) rats served as controls. PGP was determined by immunohistochemistry either 1 or 2 weeks after the last kindled seizure, by using a monoclonal anti-PGP antibody. Six brain regions were examined ipsi- and contralateral to the BLA electrode: the BLA, the hippocampal formation, the piriform cortex, the substantia nigra, the frontal and parietal cortex, and the cerebellum. Results: In both kindled rats and controls, PGP staining was observed mainly in microvessel endothelial cells and, to a much lesser extent, in parenchymal cells. The distribution of PGP expression across brain regions was not homogeneous, but significant differences were found in both the endothelial and parenchymal expression of this protein. In kindled rats, ipsilateral PGP expression tended to be higher than contralateral expression in several brain regions, which was statistically significant in the piriform cortex and parietal cortex. However, compared with controls, no significant overexpression of PGP in capillary endothelial cells or brain parenchyma of kindled rats was seen in any ipsilateral brain region, including the BLA. For comparison with kindled rats, kainate-treated rats were used as positive controls. As reported previously, kainate-induced seizures significantly increased PGP expression in the hippocampus and other limbic brain regions. Conclusions: Amygdala-kindling does not induce any lasting overexpression of PGP in several brain regions previously involved in the kindling process. In view of the many pathophysiologic and pharmacologic similarities between the kindling model and TLE, these data may indicate that PGP overexpression in pharmacoresistant patients with TLE is a result of uncontrolled seizures but not of the processes underlying epilepsy. It remains to be determined whether transient PGP overexpression is present in kindled rats shortly after a seizure, and whether pharmacoresistant subgroups of kindled rats exhibit an increased expression of PGP. Furthermore, other multidrug transporters, such as multidrug resistance,associated protein, might be involved in the resistance of kindled rats to AEDs. [source] IL-15 and IL-16 overexpression in cutaneous T-cell lymphomas: stage-dependent increase in mycosis fungoides progressionEXPERIMENTAL DERMATOLOGY, Issue 4 2000K. Asadullah Abstract: Cytokines are of major importance for the pathogenesis of cutaneous T-cell lymphomas (CTCL). Recent data suggested that IL-15 and IL-16 are survival/growth factors for the malignant T cells in these entities. To investigate the expression of IL-15 and IL-16 in mycosis fungoides (MF) and CD30+ pleomorphic T-cell lymphoma in vivo, we established a competitive RT-PCR technique. Analyzing skin biopsies from CTCL patients at different stages in comparison to psoriatic and healthy skin, we found IL-15 and IL-16 mRNA overexpression in both CTCL entities. Remarkably, there was some evidence for a stage-dependent increase during MF progression. We found only slight overexpression in early stage MF, when only few tumor cells are detectable within the infiltrates, whereas marked overexpression was found in more advanced lesions, which are characterized by a higher density of malignant cells. These results suggested that CTCL cells themselves might produce the cytokines. To further elucidate this hypothesis, two CTCL cell lines were analyzed but gave conflicting results. Therefore, the cellular origin of the IL-15 and IL-16 overexpression in CTCL remains unclear. Considering the significant overexpression of IL-15 and IL-16 and their biological capacities it is likely that these cytokines contribute to the tumor development. So, they might be involved in growth and skin homing of CTCL cells. [source] An abnormal gene expression of the ,-adrenergic system contributes to the pathogenesis of cardiomyopathy in cirrhotic rats,HEPATOLOGY, Issue 6 2008Giulio Ceolotto Decreased cardiac contractility and ,-adrenergic responsiveness have been observed in cirrhotic cardiomyopathy, but their molecular mechanisms remain unclear. To study ,-adrenergic,stimulated contractility and ,-adrenergic gene expression patterns, 20 Wistar Kyoto rats were treated with carbon tetrachloride to induce cirrhosis and 20 rats were used as controls. Left ventricular contractility was recorded in electrically driven isolated hearts perfused at constant flow with isoproterenol (10,10 to 10,6 M). A cardiac gene expression profile was obtained using a microarray for the myocyte adrenergic pathway. The cardiac contractility maximal response to isoproterenol was significantly reduced in cirrhotic rats in comparison to control rats, whereas the half-maximal effective concentration was not different. In cirrhotic rats, cardiac gene expression analysis showed a significant overexpression of G protein alpha,inhibiting subunit 2 (G,i2), cyclic nucleotide phosphodiesterase (PDE2a), regulator of G-protein signaling 2 (RGS2), and down-expression of adenylate cyclase (Adcy3). These results indicate that overexpression of G,i2, PDE2a, and RGS2 down-regulates the ,-adrenergic signaling pathway, thus contributing to the pathogenesis of cirrhotic cardiomyopathy. (HEPATOLOGY 2008;48:1913-1923.) [source] Expression profiling in multistage hepatocarcinogenesis: Identification of HSP70 as a molecular marker of early hepatocellular carcinomaHEPATOLOGY, Issue 1 2003Makoto Chuma Hepatocellular carcinoma (HCC) associated with chronic liver disease evolves from precancerous lesions and early HCC to a progressed form. Nodule-in-nodule,type HCC (progressed HCC within early HCC) represents the transition from early to progressed HCC and, therefore, is useful in molecular genetic analysis of HCC progression during multistage carcinogenesis. We compared expression profiles among 7 early components and 7 progressed components of nodule-in-nodule,type HCCs and their corresponding noncancerous liver tissues with oligonucleotide array. Of the approximately 12,600 genes that were analyzed, a set of 95 genes provided a molecular signature that distinguished between early HCC components and their noncancerous liver tissues, and a set of 92 genes distinguished between progressed and early HCC components. Of these genes, the most abundantly up-regulated gene in early HCC components (P < .001) was heat-shock protein 70 (HSP70). Real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) confirmed this finding. Further immunohistochemical examination of HSP70 revealed its significant overexpression in early HCC compared with precancerous lesions (P < .001) and in progressed HCC compared with early HCC (P < .001). In conclusion, molecular signatures were clearly different in noncancerous liver tissue as compared with the early and progressed components of nodule-in-nodule,type HCC. Moreover, HSP70 could be a sensitive marker for the differential diagnosis of early HCC from precancerous lesion or noncancerous liver, a difficult distinction for pathologists due to very well differentiated histology with little atypia in early HCC. [source] Gene Expression Profiling in Paget's Disease of Bone: Upregulation of Interferon Signaling Pathways in Pagetic Monocytes and Lymphocytes,,§JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2008Zsolt B Nagy Abstract We examined the gene expression profile of genes involved in bone metabolism in 23 patients with PD compared with 23 healthy controls. We found a significant overexpression of the genes of the IFN pathway along with a downregulation of tnf-,. Our result suggest that IFN-mediated signaling may play important roles in aberrant osteoclastogenesis of PD. Introduction: Paget's disease of bone (PD) is characterized by focal regions of highly exaggerated bone remodeling and aberrant osteoclastogenesis. Under physiological conditions, circulating monocytes may serve as early progenitors of osteoclasts and along with peripheral blood lymphocytes produce a wide variety of factors important in bone metabolism. Nevertheless, little is known about the roles of circulating monocytes and lymphocytes in relation to the pathological bone turnover in PD. Materials and Methods: In this study, we aimed at investigating the gene expression pattern of PD using quantitative real-time PCR in monocytes and lymphocytes isolated from peripheral blood mononuclear cells (PBMCs). Fifteen genes known to be involved in osteoclastogenesis were studied in cells from 23 patients with PD and in cells from 23 healthy controls. Eight human genes including ifn-, (3.48-fold, p < 0.001), ifn-, (2.68-fold, p < 0.001), ifn-, (1.98-fold, p = 0.002), p38 ,2 mapk (2.47-fold, p = 0.002), ifn-,r1 (2.03-fold, p = 0.01), ifn-,r2 (1.81-fold, p = 0.02), stat1 (1.57-fold, p = 0.037), and tnf-, (,2.34, p < 0.001) were found to be significantly altered in pagetic monocytes compared with monocytes of healthy controls. Results: In pagetic lymphocytes, significant changes in the expression of ifn-, (2.17-fold, p < 0.001), ifn-, (2.13-fold, p = 0.005), ifn-, (1.89-fold, p < 0.001), ifn-,r1 (1.02-fold, p = 0.04), ifn-,r2 (1.01-fold, p = 0.031), stat2 (1.79-fold, p < 0.001), and tnf-, (,1.49, p < 0.001) were found compared with lymphocytes of healthy controls. Furthermore, IFN-, protein was significantly elevated in the sera of PD patients (18.7 ± 6.69 pg/ml) compared with healthy controls (3.87 ± 6.48 pg/ml, p = 0.042). Conclusions: In conclusion, our data suggest that novel pathways mainly related to the IFN-mediated signaling may play important roles in the aberrant osteoclastogenesis of PD. [source] Progressive up-regulation of genes encoding DNA methyltransferases in the colorectal adenoma-carcinoma sequenceMOLECULAR CARCINOGENESIS, Issue 9 2007Wolfgang M. Schmidt Abstract Epigenetic silencing is a prominent feature of cancer. Here, we investigated the expression of DNA demethylase and three DNA methyltransferases during colorectal tumorigenesis comparing the genes encoding DNA methyltransferases 1 (DNMT1), 3A, and 3B (DNMT3A and DNMT3B) with methyl-CpG binding domain protein 2 (MBD2), recently described as the only active DNA demethylase. Total RNA isolated from normal colonic mucosa (n,=,24), benign adenomas (n,=,18), and malignant colorectal carcinomas (n,=,32) was analyzed by reverse transcriptase-PCR with subsequent quantification by capillary gel electrophoresis. In contrast to MBD2, expression of DNMT1 and DNMT3A increased in parallel to the degree of dysplasia, with significant overexpression in the malignant lesion when compared with mucosa or with benign lesions (DNMT1). Pairwise comparisons between tumors and matched, adjacent healthy mucosa tissue (n,=,13) revealed that expression of all three genes encoding DNA methyltransferases increased by two- to three-fold. Our data suggest a relevant role of the DNA methyltransferases during colorectal tumorigenesis. This increase is not counterbalanced by enhanced expression of the demethylating component MBD2. As a consequence, epigenetic regulation in the adenoma-carcinoma sequence may be driven by increased methylating activity rather than suppressed demethylation. © 2007 Wiley-Liss, Inc. [source] E1A-F is overexpressed early in human colorectal neoplasia and associated with cyclooxygenase-2 and matrix metalloproteinase-7MOLECULAR CARCINOGENESIS, Issue 1 2005William M. Boedefeld II Abstract Studies suggest the expression of cyclooxygenase-2 (COX-2) and matrilysin (MMP-7) increase in the early stages of colorectal carcinogenesis, however their interaction with other molecular markers is poorly understood. Results from cell line studies and mouse models suggest polyomavirus enhancer activator 3 (PEA3) may play a role in the activation of COX-2 and MMP-7 promoters. However, the role of E1A-F, the human homolog of murine PEA3, in colorectal cancer (CRC) development has not been elucidated. In this study, we used real-time reverse transcription (RT)-polymerase chain reaction (PCR) to measure the levels of E1A-F, COX-2, and MMP-7 in matched normal mucosa, adenomas, and/or carcinomas from 128 patients. Our results demonstrate significant overexpression of E1A-F and MMP-7 in adenomas and E1A-F, COX-2, and MMP-7 in carcinomas. In carcinomas, E1A-F expression was significantly associated with both COX-2 and MMP-7 overexpression. These results suggest E1A-F is overexpressed in early stages of human CRC development and may be an important factor in the overexpression of COX-2 and MMP-7. © 2005 Wiley-Liss, Inc. [source] Association of the interleukin-23 receptor gene variant rs11209026 with Crohn's disease in German childrenACTA PAEDIATRICA, Issue 5 2010M Lacher Abstract Aim:, Genome-wide association studies have described variants within the interleukin-23 receptor (IL23R) locus to be associated with Crohn's disease (CD) and ulcerative colitis (UC). We investigated the association of rs11209026 (p.Arg381Gln) and rs7517847 (c.799-3588T>G) into German paediatric inflammatory bowel disease (IBD) patients and analysed IL23R transcriptional activity in colonic tissues. Methods:, The rs11209026 and rs7517847 nucleotide substitutions were determined in 353 German children with IBD (221 CD, 132 UC) and 253 controls using pre-designed TaqMan® SNP genotyping assays. In selected IBD patients and controls, IL23R mRNA expression was measured using real-time PCR. Results:, The prevalence of the rs11209026 A allele was lower in CD patients, but not in UC patients, when compared with controls (1.8% vs 7.1%, p < 0.01). The rs7517847 variant, in contrast, was associated neither with CD nor with UC. IL23R expression was variable in IBD patients compared with controls without significant overexpression or downregulation. Conclusion:, Our study provides additional support for the strong protection of the rs11209026 (p.Arg381Gln) variant against paediatric CD. IL23R was expressed in both CD and UC with a great variability. However, expression levels showed no significant association with the disease. [source] | ||||||||||