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Pfister SM

Sarah A Laurent, Franziska S Hoffmann, Peer-Hendrik Kuhn, Qingyu Cheng, Yuanyuan Chu, Marc Schmidt-Supprian, Stefanie M Hauck, Elisabeth Schuh, Markus Krumbholz, Heike Rübsamen, Johanna Wanngren, Mohsen Khademi, Tomas Olsson, Tobias Alexander, Falk Hiepe, Hans-Walter Pfister, Frank Weber, Dieter Jenne, Hartmut Wekerle, Reinhard Hohlfeld, Stefan F Lichtenthaler, Edgar Meinl
Survival of plasma cells is regulated by B-cell maturation antigen (BCMA), a membrane-bound receptor activated by its agonist ligands BAFF and APRIL. Here we report that γ-secretase directly cleaves BCMA, without prior truncation by another protease. This direct shedding is facilitated by the short length of BCMA's extracellular domain. In vitro, γ-secretase reduces BCMA-mediated NF-κB activation. In addition, γ-secretase releases soluble BCMA (sBCMA) that acts as a decoy neutralizing APRIL. In vivo, inhibition of γ-secretase enhances BCMA surface expression in plasma cells and increases their number in the bone marrow...
June 11, 2015: Nature Communications
Michael Amann, Michaela Andělová, Armanda Pfister, Nicole Mueller-Lenke, Stefan Traud, Julia Reinhardt, Stefano Magon, Kerstin Bendfeldt, Ludwig Kappos, Ernst-Wilhelm Radue, Christoph Stippich, Till Sprenger
Brain atrophy has been identified as an important contributing factor to the development of disability in multiple sclerosis (MS). In this respect, more and more interest is focussing on the role of deep grey matter (DGM) areas. Novel data analysis pipelines are available for the automatic segmentation of DGM using three-dimensional (3D) MRI data. However, in clinical trials, often no such high-resolution data are acquired and hence no conclusions regarding the impact of new treatments on DGM atrophy were possible so far...
2015: NeuroImage: Clinical
Franziska S Hoffmann, Peer-Hendrik Kuhn, Sarah A Laurent, Stefanie M Hauck, Kerstin Berer, Simone A Wendlinger, Markus Krumbholz, Mohsen Khademi, Tomas Olsson, Martin Dreyling, Hans-Walter Pfister, Tobias Alexander, Falk Hiepe, Tania Kümpfel, Howard C Crawford, Hartmut Wekerle, Reinhard Hohlfeld, Stefan F Lichtenthaler, Edgar Meinl
BAFF and a proliferation-inducing ligand (APRIL), which control B cell homeostasis, are therapeutic targets in autoimmune diseases. TACI-Fc (atacicept), a soluble fusion protein containing the extracellular domain of the BAFF-APRIL receptor TACI, was applied in clinical trials. However, disease activity in multiple sclerosis unexpectedly increased, whereas in systemic lupus erythematosus, atacicept was beneficial. In this study, we show that an endogenous soluble TACI (sTACI) exists in vivo. TACI proteolysis involved shedding by a disintegrin and metalloproteinase 10 releasing sTACI from activated B cells...
January 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Frank DiPaola, Pranavkumar Shivakumar, Janet Pfister, Stephanie Walters, Gregg Sabla, Jorge A Bezerra
UNLABELLED: Peribiliary glands (PBGs) are clusters of epithelial cells residing in the submucosal compartment of extrahepatic bile ducts (EHBDs). Though their function is largely undefined, they may represent a stem cell niche. Here, we hypothesized that PBGs are populated by mature and undifferentiated cells capable of proliferation in pathological states. To address this hypothesis, we developed a novel whole-mount immunostaining assay that preserves the anatomical integrity of EHBDs coupled with confocal microscopy and found that PBGs populate the entire length of the extrahepatic biliary tract, except the gallbladder...
October 2013: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Hyun Hor, Luca Bartesaghi, Zoltán Kutalik, José L Vicário, Clara de Andrés, Corinne Pfister, Gert J Lammers, Nicolas Guex, Roman Chrast, Mehdi Tafti, Rosa Peraita-Adrados
Narcolepsy is a rare sleep disorder characterized by excessive daytime sleepiness and cataplexy. Familial narcolepsy accounts for less than 10% of all narcolepsy cases. However, documented multiplex families are very rare and causative mutations have not been identified to date. To identify a causative mutation in familial narcolepsy, we performed linkage analysis in the largest ever reported family, which has 12 affected members, and sequenced coding regions of the genome (exome sequencing) of three affected members with narcolepsy and cataplexy...
September 9, 2011: American Journal of Human Genetics
A Bouzouita, F Dugardin, A Safsaf, L Sibert, C Pfister, P Grise
The incidence of vesicoureteral reflux (VUR) varies between 10% and 80% of transplanted kidneys. In cases of failure of endoscopic treatment or recurrent urinary tract infections, surgical correction is proposed by ureteral reimplantation or pyeloureteral anastomosis using the native ureter. The aim of this study was to assess the results of a technique that increases the submucosal length of the ureter without a ureterovesical reimplantation. We treated 12 patients with VUR in the transplanted kidney by open surgery...
December 2010: Transplantation Proceedings
S Nischwitz, S Cepok, A Kroner, C Wolf, M Knop, F Müller-Sarnowski, H Pfister, P Rieckmann, B Hemmer, M Ising, M Uhr, T Bettecken, F Holsboer, B Müller-Myhsok, F Weber
OBJECTIVES: Recently, associations of several single-nucleotide polymorphisms (SNPs) within the CLEC16A gene with multiple sclerosis (MS), type-I diabetes, and primary adrenal insufficiency were reported. METHODS: We performed linkage disequilibrium (LD) fine mapping with 31 SNPs from this gene, searching for the region of highest association with MS in a German sample consisting of 603 patients and 825 controls. RESULTS: Four SNPs located in intron 19 of the CLEC16A gene were found associated...
June 2011: Acta Neurologica Scandinavica
Sandra Nischwitz, Sabine Cepok, Antje Kroner, Christiane Wolf, Matthias Knop, Felix Müller-Sarnowski, Hildegard Pfister, Darina Roeske, Peter Rieckmann, Bernhard Hemmer, Marcus Ising, Manfred Uhr, Thomas Bettecken, Florian Holsboer, Bertram Müller-Myhsok, Frank Weber
In a genome wide association study consisting of 592 German multiple sclerosis (MS) patients and 825 controls we were able to replicate the association of the HLA region with MS independently of previous case control studies. No SNPs outside the HLA region reached a genome wide level of significance. Nevertheless, we found suggestive evidence for an association of MS with variants in two new genes, the VAV2 gene and the gene for ZNF433.
October 8, 2010: Journal of Neuroimmunology
Hela-Felicitas Petereit, Dirk Reske, Hayrettin Tumani, Sven Jarius, F Markus Leweke, Dirk Woitalla, Hans-Walter Pfister, Andrea Rubbert
Neurosarcoidosis (NS) represents an important differential diagnosis of multiple sclerosis (MS). However, thus far no reliable laboratory marker of neurosarcoidosis exists. The objective of this study was to evaluate whether cerebrospinal fluid (CSF) levels of soluble interleukin 2 receptor (sIL2-R) distinguish NS and other inflammatory disorders of the central nervous system. For this purpose, 139 paired CSF and serum samples from 11 patients with NS, 21 with MS, 10 with CNS vasculitis, 22 with bacterial meningitis, 17 with viral meningitis/encephalitis, seven with neurotuberculosis, and 18 healthy donors were assessed for sIL2-R using an enzyme-linked immunosorbent assay...
November 2010: Journal of Neurology
Vesna Cvetkovic-Lopes, Laurence Bayer, Stéphane Dorsaz, Stéphanie Maret, Sylvain Pradervand, Yves Dauvilliers, Michel Lecendreux, Gert-Jan Lammers, Claire E H M Donjacour, Renaud A Du Pasquier, Corinne Pfister, Brice Petit, Hyun Hor, Michel Mühlethaler, Mehdi Tafti
Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and attacks of muscle atonia triggered by strong emotions (cataplexy). Narcolepsy is caused by hypocretin (orexin) deficiency, paralleled by a dramatic loss in hypothalamic hypocretin-producing neurons. It is believed that narcolepsy is an autoimmune disorder, although definitive proof of this, such as the presence of autoantibodies, is still lacking. We engineered a transgenic mouse model to identify peptides enriched within hypocretin-producing neurons that could serve as potential autoimmune targets...
March 2010: Journal of Clinical Investigation
Wolfgang K Pfisterer, Stephen Papadopoulos, Denise A Drumm, Kris Smith, Mark C Preul
OBJECTIVE: For frameless stereotaxy, users can choose between anatomic landmarks (ALs) or surface fiducial markers (FMs) for their match points during registration to define an alignment of the head in the physical and radiographic image space. In this study, we sought to determine the concordance among a point-merged FM registration, a point-merged AL registration, and a combined point-merged anatomic/surface-merged (SM) registration, i.e., to determine the accuracy of registration techniques with and without FMs by examining the extent of agreement between the system-generated predicted value and physical measured values...
March 2008: Neurosurgery
T A Rupprecht, H W Pfister, B Angele, S Kastenbauer, B Wilske, U Koedel
Using protein expression profiling, the authors identified an upregulation of the chemokine B lymphocyte chemoattractant (BLC) in the CSF of patients with neuroborreliosis but not in patients with noninflammatory and various other inflammatory neurologic diseases. This upregulation was confirmed by ELISA, showing increased BLC levels in every neuroborreliosis patient while being undetectable in patients with noninflammatory neurologic diseases. These results point to BLC as a putative additional diagnostic marker for neuroborreliosis...
August 9, 2005: Neurology
Johannes Jongen, Jens-Uwe Bock, Hans-Günter Peleikis, Anne Eberstein, Karin Pfister
Although stapled anopexy for second and third degree hemorrhoids has been widely used since 1998, there are limited long-term data available. We performed an analysis of a prospectively accrued data set of all patients undergoing stapled anopexy in our practice from 1998 through August 2003. Patients were specifically assessed for early and late complications and long-term reoperation rates for anorectal pathology. We performed stapled anopexy in 654 patients (296 females) during the study period. Mean operation time was 21 min (5-70 min), and the postoperative stay was 3...
March 2006: International Journal of Colorectal Disease
B F Becker, S Kastenbauer, U Ködel, D Kiesl, H W Pfister
Urate is largely excluded from the brain under non-inflammatory conditions (concentration gradient serum:CSF about 10:1), but increases markedly in Guillain-Barré Syndrome and bacterial meningitis. The oxidation product allantoin is normally not passively distributed between blood and cerebrospinal fluid (gradient 3:1) and increases 5-fold in CSF of patients with meningitis. Patients with multiple sclerosis had normal levels of urate and allantoin in blood and CSF.
October 2004: Nucleosides, Nucleotides & Nucleic Acids
Erica J Carrier, Christopher S Kearn, Andrew J Barkmeier, Nicole M Breese, Wenqi Yang, Kasem Nithipatikom, Sandra L Pfister, William B Campbell, Cecilia J Hillard
Microglia, as phagocytes and antigen-presenting cells in the central nervous system, are activated in such disease processes as stroke and multiple sclerosis. Because peripheral macrophages are capable of producing endocannabinoids, we have examined endocannabinoid production in a macrophage-colony stimulating factor (M-CSF)-dependent rat microglial cell line (RTMGL1) using reversed phase high-pressure liquid chromatography and liquid chromatography-mass spectroscopy. We determined that cultured microglial cells produce the endocannabinoid 2-arachidonylglycerol (2-AG) as well as anandamide in smaller quantities...
April 2004: Molecular Pharmacology
Stefan Kastenbauer, Uwe Koedel, Manfred Wick, Bernd C Kieseier, Hans-Peter Hartung, Hans-Walter Pfister
The new CX(3)C-chemokine fractalkine (CX(3)CL1) was measured by Western blot in the cerebrospinal fluid (CSF) and serum of patients with inflammatory diseases of the peripheral and central nervous system (Bell's palsy, BP; Guillain-Barré Syndrome, GBS; multiple sclerosis, MS; viral meningitis, VM; bacterial meningitis, BM) and patients with noninflammatory neurological diseases (controls). In controls, fractalkine was detectable at low concentrations in the CSF and, at much higher levels, in serum. In all inflammatory neurological diseases under study, CSF fractalkine levels were significantly (p<0...
April 2003: Journal of Neuroimmunology
C W Cotman, N P Hailer, K K Pfister, I Soltesz, M Schachner
Brain plasticity and the mechanisms controlling plasticity are central to learning and memory as well as the recovery of function after brain injury. While it is clear that neurotrophic factors are one of the molecular classes that continue to regulate brain plasticity in the adult central nervous system (CNS), less appreciated but equally profound is the role of cell adhesion molecules (CAMs) in plasticity mechanisms such as long term potentiation, preservation of neurons and regeneration. Ironically, however, CAMs can also reorganize the extra-cellular space and cause disturbances that drive the development of brain pathology in conditions such as Alzheimer's disease and multiple sclerosis...
August 1998: Progress in Neurobiology
A r Sousa, R Pfister, P E Christie, S J Lane, S M Nasser, M Schmitz-Schumann, T H Lee
BACKGROUND: There are two isoforms of cyclo-oxygenase (COX), namely COX-1 and COX-2. COX-1 is constitutively expressed in most tissues and in blood platelets. The metabolites derived from COX-1 are probably involved in cellular housekeeping functions. COX-2 is expressed only following cellular activation by inflammatory stimuli and is thought to be involved in inflammation. METHODS: The expression of COX-1 and COX-2 isoenzymes has been studied in the bronchial mucosa of 10 normal and 18 asthmatic subjects, 11 of whom had aspirin-sensitive asthma (ASA) and seven had non-aspirin-sensitive asthma (NASA) RESULTS: There was a significant fourfold and 14-fold increase, respectively, in the epithelial and submucosal cellular expression of COX-2, but not of COX-1, in asthmatic patients...
November 1997: Thorax
A R Sousa, B E Lams, R Pfister, P E Christie, M Schmitz, T H Lee
Increased numbers of eosinophils and mast cells in the bronchial mucosa are characteristic features in subjects with aspirin-sensitive asthma. Interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are involved in the activation, maturation, and perpetuation of survival of eosinophils. Immunohistochemical techniques were therefore used to study the expression of IL-5 and GM-CSF on frozen bronchial biopsies from 13 aspirin-sensitive asthmatic (ASA) and 8 non-ASA (NASA) subjects. Aspirin sensitivity was diagnosed by lysine-aspirin inhalation provocation...
November 1997: American Journal of Respiratory and Critical Care Medicine
H Yoshinaga, Y Hirata, C Fujiyama, Y Ichigi, A Iguchi, Z Masaki, K Nanri
In comparison with megaureters in children, their reports in adult are not common. We had an opportunity to treat seven adults with megaureters during the last six years. They were all female and ages ranged from 46 to 67 years. Five patients with grade II and one with grade III (Pfister-Hendren's classification) were treated by reconstructive surgery, excision of the narrow segment, tapering of the dilated lower ureter and reimplantation through a submucosal tunnel. The outcome of all the grade II patients was excellent and the case with grade III showed mild improvement...
February 1995: Nihon Hinyōkika Gakkai Zasshi. the Japanese Journal of Urology
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