Histology and histopathology Vol.28, nº 6 (2013)
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- PublicationOpen AccessImmunohistochemical analysis of angiotensin converting enzyme in sardinian pterygium(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2013) Demurtas, Paolo; Di Girolamo, Nick; Corrias, Michela; Zucca, Ignazio; Maxia, Cristina; Diana, Andrea; Piras, Franca; Lai, Simone; Sirigu, Paola; Perra, TeresaPterygium is a common ocular surface disorder characterized by excessive cell proliferation, inflammation, fibrosis, angiogenesis and extracellular matrix remodeling. The Angiotensin converting enzyme (ACE or ACE I) is the major component of the Reninangiotensin system (RAS) converting the inactive decapeptide Angiotensin I (Ang I) to the active octapeptide Angiotensin II (Ang II). Besides this ‘classical role’, it can act as transcriptional regulator in response to external stimuli that may lead to cell damage and tissue remodeling. Due to this role, it can be internalized into the nuclear compartment to act as transcriptional factor for proteins involved in the inflammatory response. The aim of the present study was to determine ACE expression and localization in pterygium and culture pterygium cells by immunohistochemistry. Our results are the first to demonstrate nuclear immunolocalization of ACE, more so in pterygium compared to conjunctiva epithelial cells in histological sections. ACE was not detected in the nuclei of subcultivated pterygium epithelial cells. The nuclear localization of ACE may be correlated with an antiinflammatory path mediated by activation of its transcriptional role.
- PublicationOpen AccessDifferential expression of proteins related to smooth muscle cells and myofibroblasts in human thoracic aortic aneurysm(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2013) Forte, Amalia; Della Corte, Alessandro; Grossi, Mario; Bancone, Ciro; Maiello, Ciro; Galderisi, Umberto; Cipollaro, MarilenaObjectives: Increasing knowledge is required for a better comprehension of the etiology of thoracic aortic aneurysm (TAA). The aim of this study was to highlight the modulations in vascular cell phenotypes, including myofibroblasts (MFs), in human TAA specimens compared to healthy aortas. Methods: histology, RT-PCR and immunohistochemical analysis of a panel of molecules, including EDA Fibronectin (Fn), smoothelin, CD34 and alpha-smooth muscle actin (alpha-SMA), selected on the basis of their informative potential as markers of smooth muscle cells (SMCs) and MF phenotypic modulation, were performed on all samples. Results: The media of TAAs was characterized by the absence of smoothelin, the unaltered expression of alpha-SMA accompanied by an alteration of its distribution pattern, and by the activated expression of the ED-A isoform of Fn. We found a concentration of round-shaped cells exclusively in the adventitia and in the perivascular tissue of TAAs, also rich in vasa vasorum, largely expressing alpha-SMA, while a sub-population also expressed ED-A Fn and CD34. CD34 was expressed by several cells in the intima of TAAs, together with cells expressing cytoplasmatic EDA Fn and alpha-SMA in comparison to healthy aortas. Conclusion: TAA specimens show an altered expression and localization of SMC and MF differentiation markers in comparison to healthy aortas, with possible implications on remodeling.
- PublicationOpen AccessInterleukin 1 receptor antagonist (IL1RN) genetic variations condition post-orthodontic external root resorption in endodontically-treated teeth(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2013) Iglesias-Linares, Alejandro; Yañez-Vico, Rosa Mª; Ballesta-Mudarra, Sofía Ballesta-Mudarra; Ortiz-Ariza, Estefanía; Mendoza-Mendoza, Asunción; Perea-Pérez, Evelio; Moreno-Fernández, Ana Mª; Solano-Reina, Enriquey. External pical root resorption (EARR) is a frequent iatrogenic problem following orthodontic treatment in endodontically-treated teeth, about which the literature reports substantial variability in postorthodontic treatment EARR responses. The main focus of the present study is to clarify whether variants in the interleukin-1 receptor antagonist gene coding for the IL1ra protein have a positive/negative influence on EARR of endodontically-treated teeth. Ninety-three orthodontic patients were genetically screened for a single nucleotide polymorphism (SNP:rs419598) in the IL1 cluster. The sample was classified into 2 groups: group 1 (affectedgroup) showed radiographic EARR of more than 2mm; group 2 (control-group), had no EARR or EARR≤ to 2mm following orthodontic treatment on root-filled teeth. Logistic regression analysis was performed to obtain an adjusted estimate between the SNPs studied and EARR. Genotype distributions, allelic frequencies, adjusted odds ratios (OR) and 95% confidence intervals were also calculated. We found that subjects homozygous [1/1(TT)] for the IL1RN gene [OR:10.85; p=0.001;CI:95%] were at risk of EARR in root-filled teeth. Genetic variants in the antagonist axis balance of the IL1RN(rs419598) have a direct repercussion on the predisposition to post-orthodontic EARR in root-filled teeth. Variants in allele 1 of the interleukin-1 receptor antagonist gene(rs419598) are associated(p=0.001**) with an increased risk of suffering post-orthodontic EARR in root-filled teeth.
- PublicationOpen AccessImmunohistochemical expression of thymosin ß4 in ameloblastomas and odontomas(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2013) Kiyoshima, Tamotsu; Nagata, Kengo; Wada, Hiroko; Fujiwara, Hiroaki; Shiotsuka, Maho; Kihara, Makiko; Hasegawa, Kana; Someya, Hirotaka; Sakai, HidetakaAmeloblastoma is regarded to be a benign odontogenic tumor, but it is destructive, locally invasive and presents a high rate of recurrence. Thymosin ß4 (Tß4) is closely associated with tooth germ development. Tß4 also plays a role in malignant progression and invasion. However, little is known about the function of Tß4 in odontogenic tumors. Thus, we investigated Tß4 expression in ameloblastomas and compared it with odontomas. We immunohistochemically evaluated the expression of Tß4, ameloblastin (AMBN), amelogenin (AMEL) and enamelin (ENAM) in 57 samples of ameloblastomas from 40 patients, and also assessed the expression of these molecules in 11 cases of odontomas, two of ameloblastic fibro-odontomas and one of tooth germ-like structures without the formation of enamel and dentin. Tß4 signals were observed in almost all of the ameloblastomas. The signals were observed in both peripheral columnar cells and central polyhedral/angular cells. Similar findings were observed in tooth germ-like structures, and in the ameloblastomatous nests in the ameloblastic fibro-odontomas. These samples had negative results for AMBN, AMEL and ENAM. Meanwhile, Tß4 signals were not seen in the odontomas, although immunolabeling for AMBN, AMEL and ENAM was observed in the enamel matrix and in some ameloblasts. Ectomesenhymal regions in the odontomas were negative for staining with the antibodies for AMBN, AMEL and ENAM. These results suggest that Tß4 could be associated with morphogenesis and tumor invasion in the ameloblastoma, and that Tß4 may play a role in the behavior of ameloblastoma.
- PublicationOpen AccessExpression of integrins αvß3 and αvß5 and their ligands in primary and secondary central nervous system neoplasms(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2013) Mittelbronn, Michel; Warth, Arne; Meyermann, Richard; Goodman, Simon; Weller, Michael. Aims: To study the expression of integrins αvß3 and αvß5 and their ligands in tumour, stroma and endothelial cells from human glioblastoma and CNS metastases from breast, lung and skin tumours. Methods and results: Integrin and integrin ligand expression was quantified in frozen tumour surgical specimens (15 glioblastomas and breast carcinoma metastases as well as 16 lung carcinoma and melanoma metastases) using immunohistochemistry. Gene expression profiles were evaluated in glioblastomas (n=424) and in normal brain (n=11). Overall, αvß3 expression was more common than αvß5, except in tumours derived from lung. αvß3 expression was most frequent in glioblastomas and melanoma metastases. Most lung-derived tumours expressed αvß5, but expression was less frequent in other tumours; about 20% of breast-derived tumours strongly expressed αvß5. Melanoma-derived tumours did not express αvß5. Expression of integrin ligands vitronectin, fibrinogen, fibronectin and osteopontin was variable between tumours, although most tumours expressed the ligands to some extent. Marked αvß3, but not αvß5, expression was common in stroma of CNS metastases. In blood vessels, αvß3 expression was more frequent than αvß5 and more pronounced in CNS metastases than in glioblastomas. Integrin ligand expression occurred in blood vessels in most tumours. In glioblastomas, mRNA expression of αvß3, αvß5, osteopontin and fibronectin were significantly upregulated over normal brain. Conclusions: Overall, we report distinct and heterogeneous patterns of integrin expression in primary and secondary brain tumours that may be relevant to the future development of integrintargeting therapeutic approaches to brain tumours.
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