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Expression Alone (expression + alone)
Selected AbstractsCD10 expression in trichoepithelioma and basal cell carcinoma,JOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2006Teresa Tram N. Pham Background:, Trichoepithelioma (TE) is a benign neoplasm that shares both clinical and histologic features with basal cell carcinoma (BCC). However, it is important to distinguish these neoplasms. Limited immunohistochemical stains are available to separate these two tumors. Methods:, CD10 protein immunohistochemistry was performed on paraffin-embedded biopsies of 13 TE and 23 BCC diagnosed by routine microscopy. Cases were analyzed for pattern of CD10 expression by tumor cells and surrounding stroma. Results:, Twelve of 13 (92%) TE showed positive stromal immunoreactivity. Of these, eight cases also demonstrated positivity of the papilla, and two also showed positivity of the basaloid cells. No TE demonstrated epithelial expression alone. On the other hand, expression of CD10 by basaloid cells was identified in 20 (87%) cases of BCC. Stromal positivity was also identified in three cases of BCC. Condensation of CD10-positive stromal cells around basaloid nests was statistically significant in differentiating TE from BCC (p < 0.0001). Conversely, CD10-positive basaloid cells were seen predominantly in BCC (p < 0.0001). Conclusions:, This study demonstrates a statistically significant difference in CD10 staining pattern between TE and BCC. Thus, CD10 may be a useful adjunct marker in distinguishing these tumors. [source] Ethanol Tolerance Caused by slowpoke Induction in DrosophilaALCOHOLISM, Issue 5 2006Roshani. Background: The large-conductance calcium-activated potassium channel encoded by the slowpoke gene has recently been implicated in the ethanol response. Caenorhabditis elegans carrying mutations in this gene have altered ethanol sensitivity and Drosophila mutant for this gene are unable to acquire rapid tolerance to ethanol or anesthetics. In Drosophila, induction of slowpoke expression has been linked to anesthetic resistance. Methods: We used Drosophila as a model system to examine the relationship between slowpoke expression and ethanol tolerance. Real-time PCR and a reporter transgene were used to measure slowpoke induction after ethanol sedation. An inducible slowpoke transgene was used to manipulate slowpoke levels in the absence of ethanol sedation. Results: Ethanol sedation increased transcription from the slowpoke neural promoters but not from the slowpoke muscle/tracheal cell promoters. This neural-specific change was concomitant with the appearance of ethanol tolerance, leading us to suspect linkage between the two. Moreover, induction of slowpoke expression from a transgene produced a phenotype that mimics ethanol tolerance. Conclusions: In Drosophila, ethanol sedation induces slowpoke expression in the nervous system and results in ethanol tolerance. The induction of slowpoke expression alone is sufficient to produce a phenotype that is indistinguishable from true ethanol tolerance. Therefore, the regulation of the slowpoke BK-type channel gene must play an integral role in the Drosophila ethanol response. [source] Brief Definitive Report: Human visceral leishmaniasis is not associated with expansion or accumulation of Foxp3+ CD4 cells in blood or spleenPARASITE IMMUNOLOGY, Issue 7 2010R. MAURYA Summary Natural regulatory T cells (CD4+ CD25+ Foxp3+), natural regulatory T cells (nTreg), play an important role in the regulation of inflammatory immune responses. However, the immunosuppressive properties of nTreg may unfavourably affect the host's ability to clear certain infections. In human visceral leishmaniasis (VL), reports on the frequency and function of nTreg are not conclusive. A limitation of our own previous studies that did not indicate a major role for Foxp3+ nTreg in VL pathogenesis was that Foxp3 was measured by mRNA expression alone, as other tools were not available at the time. We have in this study assessed CD4+CD25+Foxp3+ cells in splenic aspirates and peripheral blood mononuclear cells (PBMC) from an extensive series of patients with VL and endemic controls (EC) by flow cytometry (FACS). The results do not show increased frequencies of Foxp3+ cells in patient with VL pre- and post-treatment, neither were they elevated when compared to PBMC of EC. We conclude that active VL is not associated with increased frequencies of peripheral Foxp3 Treg or accumulation at the site of infection. [source] Discovery of myopodin methylation in bladder cancer,THE JOURNAL OF PATHOLOGY, Issue 1 2008V Cebrian Abstract Myopodin is an actin-binding protein that shuttles between the nucleus and the cytoplasm. After identifying an enriched CpG island encompassing the transcription site of myopodin, we aimed at evaluating the potential relevance of myopodin methylation in bladder cancer. The epigenetic silencing of myopodin by hypermethylation was tested in bladder cancer cells (n = 12) before and after azacytidine treatment. Myopodin hypermethylation was associated with gene expression, being increased in vitro by this demethylating agent. The methylation status of myopodin promoter was then evaluated by methylation-specific polymerase chain reaction (MS-PCR) analyses. Myopodin was revealed to be frequently methylated in a large series of 466 bladder tumours (68.7%). Myopodin methylation was significantly associated with tumour stage (p < 0.0005) and tumour grade (p = 0.037). Myopodin expression patterns were analysed by immunohistochemistry on tissue arrays containing bladder tumours for which myopodin methylation was assessed (n = 177). The presence of low nuclear myopodin expression alone (p = 0.031) or combined with myopodin methylation (p = 0.008) was associated with poor survival. Moreover, myopodin methylation in 164 urinary specimens distinguished patients with bladder cancer from controls with a sensitivity of 65.0%, a specificity of 79.8%, and a global accuracy of 75.3%. Thus, myopodin was identified to be epigenetically modified in bladder cancer. The association of myopodin methylation and nuclear expression patterns with cancer progression and clinical outcome, together with its ability to detect bladder cancer patients using urinary specimens, suggests the utility of incorporating myopodin methylation assessment in the clinical management of patients affected by uroepithelial neoplasias. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Selective expression of connective tissue growth factor in fibroblasts in vivo promotes systemic tissue fibrosisARTHRITIS & RHEUMATISM, Issue 5 2010Sonali Sonnylal Objective Connective tissue growth factor (CTGF) is a cysteine-rich secreted matricellular protein involved in wound healing and tissue repair. Enhanced and prolonged expression of CTGF has been associated with tissue fibrosis in humans. However, questions remain as to whether CTGF expression alone is sufficient to drive fibrosis. This study was undertaken to investigate whether CTGF alone is sufficient to cause fibrosis in intact animals and whether its effects are mediated through activation of transforming growth factor , (TGF,) signaling or through distinct signal transduction pathways. Methods We generated mice overexpressing CTGF in fibroblasts under the control of the fibroblast-specific collagen ,2(I) promoter enhancer. Tissues such as skin, lung, and kidney were harvested for histologic analysis. Mouse embryonic fibroblasts were prepared from embryos (14.5 days postcoitum) for biochemical analysis. Results Mice overexpressing CTGF in fibroblasts were susceptible to accelerated tissue fibrosis affecting the skin, lung, kidney, and vasculature, most notably the small arteries. We identified a marked expansion of the myofibroblast cell population in the dermis. RNA analysis of transgenic dermal fibroblasts revealed elevated expression of key matrix genes, consistent with a fibrogenic response. CTGF induced phosphorylation of p38, ERK-1/2, JNK, and Akt, but not Smad3, in transgenic mouse fibroblasts compared with wild-type mouse fibroblasts. Transfection experiments showed significantly increased basal activity of the CTGF and serum response element promoters, and enhanced induction of the CTGF promoter in the presence of TGF,. Conclusion These results demonstrate that selective expression of CTGF in fibroblasts alone causes tissue fibrosis in vivo through specific signaling pathways, integrating cues from the extracellular matrix into signal transduction pathways to orchestrate pivotal biologic responses relevant to tissue repair and fibrosis. [source] WT1 Is Not a Reliable Marker to Distinguish Reactive from Neoplastic Astrocyte Populations in the Central Nervous SystemBRAIN PATHOLOGY, Issue 6 2010T. David Bourne MD Abstract A diagnostic difficulty in neuropathology practice is distinguishing reactive from neoplastic astrocyte populations. This is particularly true in small biopsy samples that lack evidence of increased cellularity or mitotic activity, microvascular proliferation, or necrosis. We performed the current study to validate the previously reported finding that in the central nervous system, the expression of WT1 is limited to neoplastic astrocytes. We retrospectively studied WT1 protein expression by immunohistochemistry (IHC) in 100 formalin-fixed, paraffin-embedded brain tissue samples consisting of 3 normal control tissues, 44 cases of reactive gliosis, 49 gliomas and 4 lesions suspicious for glioma. In normal human cortex, WT1 staining was restricted to vascular endothelium. Most cases of reactive gliosis (82%) showed at least focal WT1 positivity, and analysis of specimens with electrode monitoring lesions showed an inverse relationship between WT1 expression intensity and the number of days from electrode placement to tissue resection. All glioma samples (100%) and all cases suspicious for glioma (100%) showed at least focal WT1 positivity. Our results likely differ from those in the prior report because of differences in tissue fixation and IHC methodology. Thus, our findings indicate that WT1 expression alone is not a reliable feature to distinguish reactive from neoplastic astrocytes. [source] Additional reverse transcription,polymerase chain reaction of peripheral slices is not superior to analysis of the central slice in sentinel lymph nodes from melanoma patientsBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2004H-J. Blaheta Summary Background The status of the sentinel lymph node (SLN) is an important prognostic factor in patients with cutaneous melanoma. Reverse transcription,polymerase chain reaction (RT,PCR) has been used as a sensitive means of detecting tumour cells in SLNs. Objectives To determine whether RT,PCR analysis of the SLN using both the central and the peripheral slices is more sensitive than molecular analysis of the central slice only. Methods Eighty-three SLNs from 59 patients with primary cutaneous melanoma were identified by SLN mapping. All SLNs were bisected along their longitudinal axis to produce two equal halves. One half was used for histology and immunohistochemistry, and the other was analysed by RT,PCR for tyrosinase and MelanA. Parallel to the longitudinal axis, one central slice (approximately 2 mm in thickness) was cut manually. This central slice was used for our standard RT,PCR protocol. In the current study, up to eight additional peripheral slices (each approximately 2 mm in thickness) were cut parallel to the existing cut surface. These peripheral slices were analysed by additional RT,PCR. Results Standard RT,PCR of the central slice yielded positive results in 34 of 59 patients (57%). Additional RT,PCR of peripheral slices demonstrated positive findings in six additional patients (10%) who were initially negative by standard RT,PCR of the central slice. In detail, seven of those 34 patients positive by standard RT,PCR of the central slice had positive histological findings. In each of these seven patients, RT,PCR was positive both in the central slice as well as in the peripheral slices. The remaining 27 patients with positive RT,PCR results of the central slice showed negative histological findings. Only nine (33%) of these 27 patients had a positive RT,PCR also in the peripheral slices. Finally, all 25 patients with negative RT,PCR results in the central slice showed negative histological findings. Six of these patients (24%) revealed positive RT,PCR results on the analysis of peripheral slices. However, three of these patients expressed only MelanA but not tyrosinase. Thirty lymph nodes from 24 nonmelanoma patients served as negative controls for RT,PCR. In three of these 24 patients (13%) expression of MelanA but not tyrosinase was detected by RT,PCR. Conclusions Molecular analysis of peripheral slices yielded six additional patients (10%) positive by RT,PCR who were initially negative by standard RT,PCR of the central slice. However, three of these six patients were found to express only MelanA but not tyrosinase. As MelanA expression was also found in 13% of control lymph nodes, positive MelanA expression alone in SLNs of melanoma patients requires cautious interpretation in order to avoid false-positive findings. Thus, additional molecular processing of peripheral slices did not significantly increase the number of patients with RT,PCR-positive SLNs. [source] | |||||||||||||||||||