Mullerian-Type Ciliated Cyst of the Thigh with PAX-8 and WT1 Positivity: A Case Report and Review of the Literature

Mullerian-type ciliated cysts are uncommon lesions usually found in the lower extremities and perineal region of young females. They have however been reported in males and in other anatomic sites. The cyst lining is typically positive for estrogen receptor (ER), progesterone receptor (PR), PAX-8, and WT1 immunohistochemical stains. This staining pattern has led to the notion that these cysts are of Müllerian origin. The vast majority of cases are located in the dermis where the preferred nomenclature is cutaneous ciliated cyst (CCC). We report a case of Müllerian-type ciliated cyst in the thigh of a 16-year-old girl. Unlike most of the cases reported in the English literature, this cyst was not centered in the dermis. Only a few other cases of Müllerian-type ciliated cysts with no cutaneous connection have been reported. We propose the term ectopic Müllerian cyst for this rare subset of lesions that are not skin based as is the current case

Protein Phosphatase-1α Interacts with and Dephosphorylates Polycystin-1

Polycystin signaling is likely to be regulated by phosphorylation. While a number of potential protein kinases and their target phosphorylation sites on polycystin-1 have been identified, the corresponding phosphatases have not been extensively studied. We have now determined that polycystin-1 is a regulatory subunit for protein phosphatase-1α (PP1α). Sequence analysis has revealed the presence of a highly conserved PP1-interaction motif in the cytosolic, C-terminal tail of polycystin-1; and we have shown that transfected PP1α specifically co-immunoprecipitates with a polycystin-1 C-tail construct. To determine whether PP1α dephosphorylates polycystin-1, a PKA-phosphorylated GST-polycystin-1 fusion protein was shown to be dephosphorylated by PP1α but not by PP2B (calcineurin). Mutations within the PP1-binding motif of polycystin-1, including an autosomal dominant polycystic kidney disease (ADPKD)-associated mutation, significantly reduced PP1α-mediated dephosphorylation of polycystin-1. The results suggest that polycystin-1 forms a holoenzyme complex with PP1α via a conserved PP1-binding motif within the polycystin-1 C-tail, and that PKA-phosphorylated polycystin-1 serves as a substrate for the holoenzyme

MicroRNA Profiling in Mucosal Biopsies of Eosinophilic Esophagitis Patients Pre and Post Treatment with Steroids and Relationship with mRNA Targets

<div><h3>Background</h3><p>The characterization of miRNAs and their target mRNAs involved in regulation of the immune process is an area of intense research and relatively little is known governing these processes in allergic inflammation. Here we present novel findings defining the miRNA and mRNA transcriptome in eosinophilic esophagitis (EoE), an increasing recognized allergic disorder.</p> <h3>Methods</h3><p>Esophageal epithelial miRNA and mRNA from five paired biopsies pre- and post-treatment with glucocorticosteroids were profiled using Taqman and Affymetrix arrays. Validation was performed on additional paired biopsies, untreated EoE specimens and normal controls. Differentially regulated miRNAs and mRNAs were generated, within which miRNA-mRNA target pairs with high predicted confidence were identified.</p> <h3>Results</h3><p>Compared to the post-glucocorticoid treated esophageal mucosa, of all the 377 miRNA sequences examined, 32 miRNAs were significantly upregulated and four downregulated in the pre-treated biopsies. MiR-214 was the most upregulated (150 fold) and miR-146b-5b, 146a, 145, 142-3p and 21 were upregulated by at least 10 fold. Out of 12 miRNAs chosen for validation by qRT-PCR, five (miR-214, 146b-5p, 146a, 142-3p and 21) were confirmed and 11 shared the same trend. When the expression of the 12 miRNAs in the EoE mucosa was compared to unrelated normal mucosa, six (miR-214, 146b-5p, 146a, 21, 203, and 489) showed similar significant changes as in the paired samples and 10 of them shared the same trend. In the same five pairs of samples used to profile miRNA, 311 mRNAs were down-regulated and 35 were up-regulated in pre-treated EoE mucosa. Among them, 164 mRNAs were identified as potential targets of differentially regulated miRNAs. Further analysis revealed that immune-related genes, targeted and non-targeted by miRNAs, were among the most important genes involved in the pathogenesis of EoE.</p> <h3>Conclusions</h3><p>Our findings add to the accumulating body of data defining a regulatory role for miRNA in immune and allergic processes.</p> </div

List of 69 Immune related genes targeted by differentially regulated miRNAs in EoE epithelium.

*<p>Genes related to “hypersensitivity response”, “immunological disease”, “inflammatory disease”, and “inflammatory response” by IPA annotation are selected to represent immune related genes.</p

A total of 164 mRNAs targeted by 31 miRNAs (25 target sites)^* differentially regulated in EoE epithelium.

*<p>Only up to 10 mRNAs with the highest fold change are listed under each miRNA.</p>**<p>miR-339-3p, miR-489, miR-361-5p, miR-324-5p, and miR-139-3p do not have predicted targets in combined gene list.</p

Taqman Array data of differentially regulated miRNAs in esophageal epithelium of EoE patients before vs following treatment with glucocorticosteroids.

*<p>Paired Student’s T-test; comparing the expression levels before and after treatment.</p>**<p>Fold change  =  expression levels before/after treatment.</p

Treatment-induced miRNA expression changes validated by qRT-PCR.

<p>Delta Ct values are used to represent selected miRNA expression levels in esophageal epithelium of 7 paired EoE patients pre- vs post-treatment (5 pairs used in miRNA profiling and 2 additional pairs; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0040676#pone-0040676-t001" target="_blank">Table 1</a>). Asterisks indicate statistical significance (P<0.05).</p

Functional pathway network analysis of 346 differentially regulated mRNAs.

<p>One of the primary pathway networks is associated with network functions of “Inflammatory Response, Cell-To-Cell Signaling and Interaction, Hematological System Development and Function”.</p

Clinical features of the eosinophilic esophagitis patients.

<p>Abbreviations used: Ab, Abdominal; Wt, weight; FTT, Failure to Thrive; Bud, Budesonide; Flu, Fluticasone.</p