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Background Microalbuminuria is an early lesion during the development of diabetic nephropathy. The loss of high molecular weight proteins in the urine is usually associated with decreased expression of slit diaphragm proteins. Nephrin, is the major component of the glomerular slit diaphragm and loss of nephrin has been well described in rodent models of experimental diabetes as well as in human diabetic nephropathy. Methodology/principal findings In this manuscript we analyzed the role of PKC-alpha (PKCalpha) on endocytosis of nephrin in podocytes. We found that treatment of diabetic mice with a PKCalpha-inhibitor (GO6976) leads to preserved nephrin expression and reduced proteinuria. In vitro, we found that high glucose stimulation would induce PKCalpha protein expression in murine and human podocytes. We can demonstrate that PKCalpha mediates nephrin endocytosis in podocytes and that overexpression of PKCalpha leads to an augmented endocytosis response. After PKC-activation, we demonstrate an inducible association of PKCalpha, PICK1 and nephrin in podocytes. Moreover, we can demonstrate a strong induction of PKCalpha in podocytes of patients with diabetic nephropathy. Conclusions/significance We therefore conclude that activation of PKCalpha is a pathomechanistic key event during the development of diabetic nephropathy. PKCalpha is involved in reduction of nephrin surface expression and therefore PKCalpha inhibition might be a novel target molecule for anti-proteinuric therapy.

Background: An inappropriate activation of the mTOR pathway was demonstrated in the autosomal dominant (AD) form of polycystic kidney disease (PKD). To date it is unclear whether the mTOR pathway is activated in autosomal-recessive (AR) PKD, a cystic disease which occurs in childhood. The purpose of the present study was to evaluate the mTOR pathway in AR PKD. Methods: We evaluated the expression of mTOR pathway molecules in paraffin-embedded liver and kidney samples from patients with AR PKD and control specimens from animals as well as humans. Monoclonal antibodies, the phosphorylated proteins pmTOR, pS6-ribosomal-protein (pS6K), p4E-BP1, peIF4G, and phospho-tuberin/TSC2 were used. Results: mTOR was strongly expressed in renal cyst-lining cells and bile ducts from AR PKD specimen. S6K immunostaining was strong in smaller tubules and weak both in larger renal cysts and in the bile duct epithelium. In controls, mTOR and S6K were expressed in distal tubule segments. 4E-BP1-immunostaining was restricted to noncystic tubules in AR PKD. eIFG4-immunostaining was observed in bile duct epithelium in AR PKD, but not in control tissue. Tuberin/TSC2 immunostaining was negative in all specimens. Conclusion: Our data suggest that the mTOR pathway may be activated in AR PKD, and mTOR molecules may represent a potential target to slow down cyst development in this disease.

Ischemia remains the most common cause of acute kidney injury (AKI). Decreased intercellular adhesion and alterations in adhesion molecules may contribute to the loss of renal function observed in AKI. In the present study, we evaluated the distribution of adhesion molecules in the human kidney and analyzed their expression in human and experimental AKI. Specimens of human kidneys obtained from patients with and without AKI were stained for the cell adhesion molecules E-cadherin, N-cadherin and beta-catenin. Experimental AKI in rats was induced by renal artery clamping. Immunostaining and immunoblotting were carried out for E-cadherin, N-cadherin and beta-catenin. Proximal tubule cells from opossum kidneys (OKs) were used to analyze the effect of chemical hypoxia (ATP depletion) in vitro. In the adult human kidney, N-cadherin was expressed in proximal tubules, while E-cadherin was expressed in other nephron segments. beta-Catenin was expressed in both proximal and distal tubules. In human AKI and in ischemic rat kidneys, N-cadherin immunostaining was depleted from proximal tubules. There was no change in E-cadherin or beta-catenin. In vitro, OK cells expressed N-cadherin only in the presence of collagen, and ATP depletion led to a depletion of N-cadherin. Collagen IV staining was reduced in ischemic rat kidneys compared to controls. The results of the study suggest that N-cadherin may play a significant role in human and experimental AKI.

Background Chronic urticaria often points the way to the diagnosis of a systemic disease, particularly when urticarial vasculitis can be demonstrated. Hypocomplementemic urticarial vasculitis syndrome (HUVS) is considered to be an independent immunological disease.

Atypical protein kinase C (aPKC) is a central component of the evolutionarily conserved Par3-Par6-aPKC complex, one of the fundamental regulators of cell polarity. We recently demonstrated that these proteins interact with Neph-nephrin molecules at the slit diaphragm of the glomerular filtration barrier. Here, we report that podocyte-specific deletion of aPKClambda/iota in mice results in severe proteinuria, nephrotic syndrome, and death at 4 to 5 wk after birth. Podocyte foot processes of knockout mice developed structural defects, including mislocalization of the slit diaphragm. In the glomerulus, aPKClambda/iota was primarily expressed in developing glomerular epithelial cells and podocyte foot processes. Interestingly, under physiologic conditions, aPKClambda/iota translocated from the apical surface to the basolateral side of developing podocytes, and this translocation preceded the development of foot processes and formation of slit diaphragms. Supporting a critical role for aPKClambda/iota in the maintenance of slit diaphragms and podocyte foot processes, aPKClambda/iota associated with the Neph-nephrin slit diaphragm complex and localized to the tips of filopodia and leading edges of cultured podocytes. These results suggest that aPKC signaling is fundamental to glomerular maintenance and development.

Frasier syndrome (FS) is characterized by chronic renal failure in early adulthood, varying degrees of gonadal dysgenesis, and a high risk for gonadal germ cell malignancies, particularly gonadoblastoma. Although it is known to arise from heterozygous splice mutations in intron 9 of the Wilms' tumor gene 1 (WT1), the mechanisms by which these mutations result in gonadal dysgenesis in humans remain obscure. Here we show that a decrease in WT1 + KTS isoforms due to disruption of alternative splicing of the WT1 gene in a FS patient is associated with diminished expression of the transcription factors SRY and SOX9 in Sertoli cells. These findings provide the first confirmation in humans of the results obtained by others in mice. Consequently, Sertoli cells fail to form the specialized environment within the seminiferous tubules that normally houses developing germ cells. Thus, germ cells are unable to fully mature and are blocked at the spermatogonial-spermatocyte stage. Concomitantly, subpopulations of the malignant counterpart of primordial germ cells/gonocytes, the intratubular germ cell neoplasia unclassified type (ITGCN), are identified. Furthermore, dysregulated Leydig cells produce insufficient levels of testosterone, resulting in hypospadias. Collectively, the impaired spermatogenesis, hypospadias and ITGCN comprise part of the developmental disorder known as 'testicular dysgenesis syndrome' (TDS), which arises during early fetal life. The data presented here show that critical levels of WT1 + KTS, SRY and SOX9 are required for normal Sertoli cell maturation, and subsequent normal spermatogenesis. To further study the function of human Sertoli cells in the future, we have established a human cell line.

Peer-to-Peer-Netzwerke haben der digitalen Distribution von Musik- und Filminhalten zum Durchbruch verholfen. Mit dem Launch des ersten File Sharing-Services „ Napster“, 1999, wurde die latente Nachfrage nach MP3-Dateien umfangreich gedeckt — und das (illegale) Herunterladen von Mediendateien und damit die Musikpiraterie zum Massenphanomen. In den Jahren zuvor machte zwar insbesondere der Anbieter MP3.com das Horen von MP3-Dateien popular-jedoch war das Angebot nur begrenzt, weil die notwendigen Lizenzen fehlten.

sided aortic arch and Kommerell diverticulum. Kommerell diverticulum (Figure 2) is a saccular aneurysmal dilation at the origin of an aberrant right or left subclavian artery. It is a rare anomaly that occurs in association with a double or left aortic arch and an aberrant right subclavian artery (0.5% of the population) or with a right aortic arch and an aberrant left subclavian artery (0.1%). Embryologically, it represents the persistent distal end of the interrupted fourth aortic arch, between the carotid and subclavian arteries. The question arises as to whether this congenital anomaly increases the likelihood of development of an AEF in response to disease or disruption. Kommerell diverticulum represents a likely area of weakening in the aortic wall that can also compress the esophagus and, in theory, could cause erosion of the structure into each other, especially when disruption of adventitial layers has occurred, such as with trauma. In summary, long-term survival can be achieved with early diagnosis and prompt surgical management of AEF. Because this condition presents in a catastrophic manner, younger and healthier patients are more likely to have better outcomes. In our case, the patient’s young age and the relatively small size of his AEF, as well as prompt diagnosis and surgical treatment, proved the ultimate determinants of success and are why he remains alive to this day.

Podocyte depletion is a critical event in glomerular diseases in general and in the development of focal segmental glomerulosclerosis in particular. Progenitor cell immigration is a possible mechanism of podocyte replacement for the preservation of nephron function since, with rare exception, mature podocytes are thought to be incapable of replication. We examined eight paraffin-embedded renal biopsies from six male recipients of female transplant kidneys for receiver-derived podocytes. Fluorescent in situ hybridization for the Y chromosome was combined with immunofluorescence for the podocyte marker, Wilms tumor-1 antigen. Recipient-derived podocytes were found in 4 of 8 biopsies representing 3 of the 6 patients. Overall, 5 of the 740 podocytes examined in the female-donated kidneys were male derived. Our study suggests that immigrating progenitor cells are able to replace podocytes in humans; however, the importance of this process in physiologic and pathologic conditions is unknown. © 2007 International Society of Nephrology.

Aim Treatment of patients with antibody-mediated rejection (AMR) after kidney transplantation with rituximab is ambiguous. Due to its unknown efficiency and serious side-effects, biomarkers, that are predictive for responsiveness to rituximab therapy in AMR patients, are required. Methods Twenty renal transplant patients were included in this retrospective study. Selection was based on Renal Index Biopsies, classified using Banff, where at least two AMR diagnostic criteria were positive within the three months prior to rituximab therapy. Patients were categorized into responders (R) and non-responders (NR) depending on whether they returned to dialysis within 6 months after initiation of rituximab treatment. Clinical, histopathological (Banff classification) and serological parameters were compared between both groups by t-test, Mann-Whitney-U-test or Likelihood-Ratio-Chi-square-test. Results In comparisons between the groups, the R group had a 1.5-fold higher level of estimated glomerular filtration rate (eGFR) and a 4-fold lower level of proteinuria. By contrast, there were no differences in the histological scores for chronic transplant lesions between the groups. The t- and i-scores were higher in NRs, whereas Banff-C4d-scores of peritubular capillaries were increased in the Rs. Transplant biopsies in the Rs exhibited more CD138+cell infiltrates. Serological determination of HLA antibodies showed higher positivity for HLA class II donor-specific antibodies in the R group. No significant differences in other clinical criteria were found. Conclusions Increased proteinuria, decreased graft function and a higher grade of tubulitis and inflammation in AMR are negative predictors for responsiveness to rituximab therapy. Rituximab therapy therefore should be initiated in an early phase of AMR.

Aim Antibody-mediated rejection (AMR) is a key limiting factor for long-term graft survival in heart and kidney transplantation. Activation of endothelial cells (ECs) via complement-independent effects of human leukocyte antigen class I (HLA I) antibodies (Abs) plays a major role in the pathogenesis of AMR. As the antioxidant enzyme heme oxygenase (HO)-1 is known to have cell type-specific anti-inflammatory effects in the endothelium, we investigated its role on HLA I Ab-dependent activation of human ECs. Methods Regulation of inducible proinflammatory endothelial adhesion molecules and chemokines (VCAM-1, ICAM-1, IL-8 and MCP-1) by monoclonal pan- and allele-specific HLA I Abs was determined in cell cultures of primary human umbilical venous, aortic macrovascular and microvascular ECs. HO-1 was modulated by pharmacological regulators and siRNA-mediated knockdown. Adherence of THP-1 monocytes to ECs was determined by leukocyte adhesion assay. Results Exposure of human macro- and microvascular EC cultures to HLA I Abs caused endothelial activation, as indicated by up-regulation of VCAM-1, ICAM-1, MCP-1 and IL-8. This up-regulation was mediated via the phosphatidylinositol-3 kinase (PI3K)/Akt and NF- κ B pathways. Pharmacological induction of HO-1 with cobalt-protoporphyrin IX reduced, whereas inhibition of HO-1 with either zinc-protoporphyrin IX or siRNA-mediated knockdown increased HLA I Ab-dependent EC activation. Binding of THP-1 monocytes was enhanced in HLA I Ab-stimulated ECs. This effect was counteracted by HO 1 up-regulation. Conclusion HLA I Ab-dependent EC activation is modulated by specific HO-1 up-regulation. Thus, targeted regulation of endothelial HO-1 may be a novel therapeutic approach for the treatment of AMR in kidney and heart transplantation. S. Immenschuh: Grant/Research Support; Company/Organization; Else Kroner-Fresenius Stiftung EKFS 2012_A309.

Hirsutism or virilization in postmenopausal women may be due to increased testosterone levels caused by an androgen-secreting tumor. The preoperative localization of small ovarian or adrenal androgen-secreting tumors is difficult.A 61-year-old, postmenopausal woman presented with progressive hirsutism and deepening of voice over the last 9 years. Serum testosterone was very high (almost 30 nmol/l). Computed tomographic (CT) scans of the adrenals and ultrasonography of the pelvis were negative. Selective catheterization and [(18)F]FDG-PET/CT investigation raised the suspicion of an androgen-secreting tumor of the right ovary. Oophorectomy was performed, and a Leydig cell tumor of the right ovary was confirmed on histological examination.Selective catheterization and [(18)F]FDG-PET investigation may aid the detection of androgen-secreting tumors.

Early manifestations of posttransplant lymphoproliferative disorders (PTLD) are mainly associated with a primary Epstein-Barr virus (EBV) infection. Rapid increases in peripheral blood EBV DNA load are supposed to reliably predict PTLD. We report a boy who 6 months after living-related kidney transplantation presented with an extranodal esophageal manifestation of PTLD. Despite a primary EBV infection with tonsillitis, the peripheral blood EBV DNA remained low, hiding the progression to PTLD.

Background: Calcineurin inhibitors (CNI) are the main immunosuppressive drugs in solid organ transplantation. However, their use is hampered by side effects like nephrotoxicity. We report an exceptional experience with three children treated with sirolimus after combined liver and kidney transplantation with prolonged renal failure and CNI-associated nephrotoxicity. Patients and results: Two girls experienced prolonged renal graft failure after combined liver-kidney transplantation for 11 and 12 weeks. Repeated biopsies did not show any rejection but did exhibit tubular damage and acute CNI-toxicity. A boy with hyperoxaluria after liver and (a third) renal transplantation experienced acute renal graft failure after an early steroid-resistant rejection. All children were switched to sirolimus-based immunosuppression and cessation of CNI therapy, which was followed by rapid improvement of renal function. Rejection of liver or kidney did not occur after CNI withdrawal. Sirolimus was commenced with 3 mg/m2/day in two doses and resulted in reasonable drug exposure. However, drug monitoring was required to adjust sirolimus dosage. Summary: Prolonged renal failure after transplantation with severe CNI toxicity may be salvaged successfully with sirolimus-based immunosuppression.

The chemokine receptor 5 Δ32 mutation is associated with increased renal survival in patients with IgA nephropathy.BackgroundChemokine receptor 5 (CCR5) plays an important role in the recruitment of monocytes and T cells in inflammation and experimental studies suggest that CCR5 might be involved in the pathogenesis of IgA nephropathy. A mutation in the CCR5 gene (CCR5 Δ32), leading to a nonfunctional receptor, was recently described. We therefore evaluated the potential role of this mutation on renal survival in patients with IgA nephropathy.MethodsThe distribution of the CCR5 Δ32 genotype was determined by polymerase chain reaction (PCR) analysis in 228 patients with biopsy-proven IgA nephropathy. In 190 patients with available demographic and clinical follow-up data, the effect of the mutation on the clinical outcome was analyzed using the Log-rank test and the Cox proportional hazard model. In vitro, the influence of the CCR5 Δ32 genotype on the chemotactic response of monocytes was assessed.ResultsOf the 190 patients, 158 (83.2%) had a CCR5 wild-type genotype, 29 (15.3%) were heterozygous, and three patients had a homozygous CCR5 Δ32 genotype (1.6%). Renal survival was significantly longer in patients with the CCR5 Δ32 genotype than in the wild-type group (Log-rank P < 0.001). Using the multivariate Cox proportional hazard model, the CCR5 Δ32 genotype was identified as an independent factor associated with a lower risk to develop end-stage renal disease (ESRD) [hazard ratio (HR) 0.23, 95% CI 0.09 to 0.57, P = 0.002]. In vitro analysis of monocytes from CCR5 Δ32 carriers showed a reduced chemotactic response to CCR5 ligands in vitro.ConclusionOur study demonstrates an independent role of the CCR5 Δ32 genotype for the clinical outcome in IgA nephropathy. In vitro experiments revealed a reduced chemotactic response of monocytes from CCR5 Δ32 carriers, thus pointing out a possible pathophysiologic explanation for the beneficial effect of the CCR5 Δ32 genotype.

In der Realitat hat sich gezeigt, dass deutliche Diskrepanzen zwischen dem tatsachlichen Verhalten und den vermeintlich rationalen Motiven der Theorie bestehen. Will man dem theoretischen Modell des Nutzungs- und Angebotsverhaltens genauer auf die Spur kommen und konkrete Verhaltensmuster zur Generierung von Implikationen identifizieren, ist es unerlasslich, sich der empirisch-quantitativen Forschung zu bedienen. Dabei ist es im Rahmen der empirischen Forschung notwendig, die zur Beantwortung der formulierten Forschungsfrage notwendigen Informationen zu sammeln und diese mit Hilfe geeigneter Methoden zu analysieren (Shugan 2002, S. 372).

Die bisherige theoretische und empirische Analyse der Angebotsmotivation der Nutzer von Peer-to-Peer-Netzwerken hat ein differenziertes Bild der Nutzerschaft gezeigt. Es wurde deutlich, dass es sich beim File Sharing trotz der rechtlichen Bedenken um einen beachtenswerten Markt handelt, fur den es sich lohnt, die Prinzipien und Handlungsweisen der Teilnehmer zu verstehen. Um die empirischen Ergebnisse mit einer inhaltlichen Dimension zu versehen, sollen daraus im folgenden Abschnitt Implikationen fur das Management abgeleitet werden. Dabei werden die Auswirkungen der Befunde und die zu treffenden Masnahmen sowohl fur die Betreiber von Tauschborsen als auch fur die Musik- und Filmindustrie diskutiert. Die Bewertung der Handlungsempfehlungen fur die Betreiber von Tauschborsen gilt dabei unabhangig von dem jeweilig betriebenen Geschaftsmodell. Den Uberlegungen liegt die grundlegende Annahme zugrunde, dass sich Freeriding zu einem existenziellen Problem des File-Sharing-Netzes auswirkt, sofern keine Masnahmen dagegen getroffen werden.

In den folgenden Abschnitten wird File Sharing als ein okonomisches Problem betrachtet und die Besonderheiten, die fur virtuelle Tauschborsen gelten, dargestellt. Gemas der Definition von Fehl und Oberender (1994, S. 10) handelt es sich bei p2p-Netzen um (virtuelle) Markte, deren Dynamik, analog zu realen Markten, durch das Zusammentreffen von Angebot und Nachfrage entsteht. Allerdings besteht ein gravierender Unterschied: Wahrend es in realen Markten zu unmittelbaren Tauschbeziehungen zwischen den Marktteilnehmern kommt, die ihre Produkte gegen Geld oder andere Produkte austauschen, fehlt in den meisten Tauschborsen ein wesentlicher Aspekt marktlicher Transaktionen. Da Dateien nicht direkt getauscht, sondern kopiert werden, fehlt im Rahmen eines indirekten Tauschs ein adaquates Tauschmittel. Somit erhalt ein Nachfrager einer Datei diese, ohne eine Kompensation zu leisten, wahrend der Anbieter im Gegenzug die Datei zur Verfugung stellt, ohne direkt vom Nachfrager kompensiert zu werden.

File Sharing, d.h. der Austausch von Dateien unter Nutzern, ist durch die Entwicklung der Tauschborsen zwar zu einem Massenphanomen geworden, es ist jedoch schon seit den Anfangen des Internet moglich (Minar und Hedlund 2001, S. 8 ff.; Schoder und Fischbach 2003b). Mit Hilfe von Internet-Services wie Internet Relay Chat (IRC) (siehe Glossar), eMail oder Instant Messaging wie ICQ konnten Verbindungen zwischen individuellen Nutzern aufgebaut und Dateien versandt werden. Im Unterschied zu den heutigen File-Sharing-Netzen beschrankte sich der Datenaustausch auf enge Communities und Kommunikation unter Bekannten. Erst mit der Entwicklung von Tauschborsen, die insbesondere durch die Indexierung der Inhalte die Suche nach Inhalten sowie den Datentransfer erleichtert haben, wurde File Sharing zu einer der meistgenutzten Anwendungen des Internet.

Die vorliegende Forschungsarbeit hat als explorative Studie zu den Motivationsformen zur Teilnahme am File Sharing einen guten Einblick in die Anreizstruktur der Nutzer gewahrt. So konnten die Ergebnisse samtliche der theoretisch hergeleiteten Motivationsformen auf Segmentebene bestatigen und sich diese zudem in einen dynamischen Kontext ubertragen lassen.

Dear Sirs, Protein kinase C (PRKC) is a family of at least twelve serine–threonine kinases and a key signaling pathway in diabetic vascular complications [1]. Our group recently demonstrated that deletion of distinct PRKC isoforms in vivo prevents from diabetes-induced kidney damage, probably depending on the individual cell type or tissue, which subsequently interferes with experimental diabetic nephropathy through independent molecular mechanisms [1]. Data on renal PRKC transcript expression profiles in the early development of human diabetic kidney damage are, however, still missing. Therefore, the aim of this pilot study was to determine the transcript expression levels of renal PRKC isoforms a, b1, c, d, e, g, h, i by real-time quantitative PCR (qPCR) in three consecutive archival control kidney biopsies of diabetic transplant recipients and to compare to case-matched, non-diabetic controls. We retrospectively analyzed data from diabetic patients (n = 11) and case-matched, non-diabetic controls (n = 11) enrolled in the protocol biopsy program of the transplant center of the Hannover Medical School which is part of the routine medical care following kidney transplantation [2]. From these two study groups, RNA-later-embedded frozen biopsy samples collected 6 weeks (K1), 3 months (K2), and 6 months (K3) after kidney transplantation were subjected to PRKC-isoform-specific qPCR. The program had been approved by the local ethical committee and is conducted in accordance with the Declaration of Helsinki. The key findings of this pilot study were that although (1) the main PRKC isoforms (a, b1, e, f) are expressed early in human kidney transplants, (2) PRKC-isoform mRNA expression does not dynamically increase over time in a diabetic milieu in the first 6 months after kidney transplantation (Fig. 1). In contrast, we observed that (3) mRNA expression of the PRKC-f isoform was significantly decreased at time point 3 (K 3; 6 months after kidney transplantation) in the diabetic group compared to non-diabetic controls. Interestingly, previous observations many years ago showed that, in addition to PRKC activation through increased serine/threonine phosphorylation under hyperglycemic condition, high glucose also induces protein expression of PRKC-isoforms a, b, and e in mesangial cells after 48 h, but not after 12 h [3]. Toyoda et al. [4] suggested for the first time that elevated expression of PRKC–MAPK pathway mRNAs correlates with glomerular lesions in patients with overt diabetic nephropathy. Recently, Langham et al. [5] postulated that increased PRKC-b transcription measured by qPCR occurs in advanced human diabetic nephropathy by analyzing human kidney biopsies with longterm DM. In contrast to the latter study, our results did not show any significant up-regulation of any PRKC-isoform transcript expression using archival biopsy tissue within the first 6 months following human kidney transplantation in diabetic compared to non-diabetic recipients. We did not find a significant correlation between PRKC-isoform mRNA expression levels and HbA1c at the three distinct time points of biopsy. We also did not observe any relationship between PRKC-isoform mRNA expression and other laboratory or Communicated by Renato Lauro.

414 Background: Significance of Urocortin (Ucn or UcnI), Ucn2, Ucn3, and their receptors, Corticotropin Releasing Factor Receptor 1 and 2 (CRFR1 and CRFR2), and the binding protein, Corticotropin-Releasing Hormone-Binding Protein (CRHBP) in oncology is growing rapidly. Recently we found that the UCN system may also be a relevant structure in renal cell cancer. Here we investigate whether CRHBP CGI methylation occurs in cc-RCC and whether its methylation is associated with clinicopathological parameters of patients. Methods: Tumoral tissues of 109 patients with renal cell cancer and their corresponding normal tissues have been used. Combined bisulfite restriction analysis (COBRA) for detection of relative degree of CpG island (CGI) methylation and pyrosequencing have been performed. Results: We found an approximately five-fold increase in mean methylation of the CRHBP CGI for tumor tissues (p < 0.00005). Higher DNA methylation of the CRHBP CGI showed a positive correlation with advanced disease as well (p = 0.024). Conclusions: To our knowledge we report for the first time the CGI methylation of CRHBP in clear cell renal cell carcinoma indicating a contribution of epigenetic alteration of CRHBP to RCC tumorigenesis. Moreover, our results suggest CRHBP as a potential molecular marker for assessment of progression and aggressiveness of tumors.

Phosphoniumfluoride sind durch Ionenaustausch zuganglich und gehen ohne Hilfsbase die Wittig-Reaktion ein. Ions, II. Wittig Olefination with Phosphonium Fluorides Phosphonium fluorides are available by ion exchange and can be used for the Wittig reaction without an auxiliary base.

Background Significance of Urocortin (Ucn or UcnI), Ucn2, Ucn3 and their receptors, Corticotropin Releasing Factor Receptor 1 and 2 (CRFR1 and CRFR2), and the binding protein, Corticotropin-Releasing Hormone-Binding Protein (CRHBP) in oncology is growing rapidly. The objective of our study was to assess the expression of the CRHBP mRNA and protein in renal cancer. Methods Tumoral tissues of 78 patients with clear cell renal cell cancer and their corresponding normal tissues were analyzed using quantitative mRNA expression analysis for detection of mRNA expression level. Protein expression and tissue localization of CRHBP protein in renal specimens was evaluated using western blotting, immunohistochemistry and double immunofluorescence, respectively. Results We found an approx. 33 fold decrease of average CRHBP mRNA level in tumoral tissues compared to paired normal tissues (p