An alternative promoter of the human plakophilin-3 gene controls the expression of the new isoform PKP3b.

The plakophilin family (PKP1 to PKP3) is an essential component of the desmosomal adhesion complex with differentiation-dependent and partially overlapping expression and possible participation of the corresponding genes in malignant transformation. Here, we describe a new protein variant of the human PKP3 gene, namely PKP3b, which differs from the published PKP3a only at the amino-terminus by the splicing in of the newly identified exon 1b. Specific antibodies have demonstrated differential expression patterns of the two variants. Whereas PKP3a is broadly expressed among epithelial cells, PKP3b is abundant in the desmosomes of stratified epithelial cells, such as HaCaT but absent or heterogeneous in simple epithelial cells such as CaCo2 or MCF7. The differential expression of the PKP3 variants has been observed in a similar manner in selected normal human tissues and carcinomas derived thereof. Both variants are localized to the desmosomes of all cells of stratified tissues, whereas the new PKP3b is heterogeneously expressed in the colon and its tumors. Therefore, we assume that both variants are controlled by alternative promoters. Reporter gene assays have confirmed that a fragment upstream of exon 1b exhibits transcriptional activity only in HaCaT cells but not in CaCo2 cells and thus has been identified as an alternative promoter driving the expression of PKP3b. Finally, by using electromobility shift assays, we found a potential binding site in the PKP3b promoter for transcription factor C/EBP regulating keratinocyte differentiation and probably also PKP3b expression. We discuss the properties of the new variant PKP3b as a possible marker protein for the analyses of differentiation and malignant transformation.

Role of ventriculoperitoneal shunt valve design in the treatment of pediatric hydrocephalus--a single center study of valve performance in the clinical setting.

PURPOSE: Previous studies have established risk factors for ventriculoperitoneal shunt failure in children. However, the role of valve type as a determinant of complications and outcome remains unclear. The aim of this study was to compare the fixed-pressure paediGAV and the programmable Codman Hakim valves in the clinical setting. METHODS: We conducted a retrospective review of patients younger than 16 years who underwent primary implantation of a ventriculoperitoneal shunt with either valve type at our institution between January 2005 and December 2010. Shunt survival analyses were performed to identify variables associated with risk of shunt failure. RESULTS: Of the 44 patients in the paediGAV cohort, 50% reached the endpoint of shunt failure with a mean time to shunt failure of 7 months. The Codman Hakim cohort comprised 29 patients, of which 55% experienced shunt failure with a mean time to shunt failure of 8 months. Stratified analyses identified young age at implantation and posthemorrhagic hydrocephalus as risk factors for shunt failure. Shunt survival analysis revealed no significant difference with regard to valve type. CONCLUSIONS: This study confirmed important risk factors for shunt failure in children. Despite certain limitations and biases, similar findings for both valves examined in the clinical setting were obtained. Thus, valve type does not seem to influence risk of shunt failure. Prospective, randomized, and controlled trials are required to validate these results.

Clinical and radiological presentation of spinal epidural haemangiomas: clinical series in a tertiary care centre during a 10-year period.

PURPOSE: Haemangiomas are very frequent benign spinal tumours. However, pure epidural location is extremely rare. At present, only 52 cases have been reported in the literature during the last 10 years. We proposed to analyse clinical and radiological features of this rare entity treated in a tertiary care centre over the last 10 years. METHODS: A study of a retrospective surgical series (2002-2012) was conducted. The clinic's electronic database was searched for "spinal" and/or "vertebral haemangiomas", which were treated by surgery and/or vertebroplasty. Clinical, radiological and histopathological data were analysed. RESULTS: In total, the series comprised 30 spinal haemangiomas. There were 6 epidural (20 %), 17 vertebral (57 %) and 7 intradural lesions (23 %). There were four men and two women, mean age 28.3 years, with epidural lesions. One patient presented with localised back pain only, two with radiculopathy and focal neurological deficit, two with radiculopathy only and one with isolated focal neurological deficit, respectively. The onset of symptoms was progressive in four cases over weeks to months and sudden in two cases. Preoperative MRI imaging revealed features of meningioma, neurinoma or metastasis. CONCLUSION: Epidural haemangiomas are extremely rare spinal lesions. They may mimic more common spinal tumours clinically and radiologically. The usual treatment is gross total resection confirming the diagnosis histologically.

The desmosomal plaque proteins of the plakophilin family.

Three related proteins of the plakophilin family (PKP1_3) have been identified as junctional proteins that are essential for the formation and stabilization of desmosomal cell contacts. Failure of PKP expression can have fatal effects on desmosomal adhesion, leading to abnormal tissue and organ development. Thus, loss of functional PKP 1 in humans leads to ectodermal dysplasia/skin fragility (EDSF) syndrome, a genodermatosis with severe blistering of the epidermis as well as abnormal keratinocytes differentiation. Mutations in the human PKP 2 gene have been linked to severe heart abnormalities that lead to arrhythmogenic right ventricular cardiomyopathy (ARVC). In the past few years it has been shown that junctional adhesion is not the only function of PKPs. These proteins have been implicated in cell signaling, organization of the cytoskeleton, and control of protein biosynthesis under specific cellular circumstances. Clearly, PKPs are more than just cell adhesion proteins. In this paper we will give an overview of our current knowledge on the very distinct roles of plakophilins in the cell.