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101.
Zacharias U Purfürst B Schöwel V Morano I Spuler S Haase H 《Journal of muscle research and cell motility》2011,32(4-5):271-280
Ahnak1 is a giant, ubiquitously expressed, plasma membrane support protein whose function in skeletal muscle is largely unknown. Therefore, we investigated whether ahnak would be influenced by alterations of the sarcolemma exemplified by dysferlin mutations known to render the sarcolemma vulnerable or by mutations in calpain3, a protease known to cleave ahnak. Human muscle biopsy specimens obtained from patients with limb girdle muscular dystrophy (LGMD) caused by mutations in dysferlin (LGMD2B) and calpain3 (LGMD2A) were investigated for ahnak expression and localization. We found that ahnak1 has lost its sarcolemmal localization in LGMD2B but not in LGMD2A. Instead ahnak1 appeared in muscle connective tissue surrounding the extracellular site of the muscle fiber in both muscular dystrophies. The entire giant ahnak1 molecule was present outside the muscle fiber and did only partially colocalize with CD45-positive immune cell infiltration and the extracelluar matrix proteins fibronectin and collagenVI. Further, vesicles shedded in response to Ca(2+) by primary human myotubes were purified and their protein content was analysed. Ahnak1 was prominently present in these vesicles. Electron microscopy revealed a homogenous population of vesicles with a diameter of about 150?nm. This is the first study demonstrating vesicle release from human myotubes that may be one mechanism underlying abnormally localized ahnak1. Taken together, our results define ahnak1 in muscle connective tissue as a novel feature of two genetically distinct muscular dystrophies that might contribute to disease pathology. 相似文献
102.
Sandra Huff Matthias Honal Tobias Baumann Jürgen Hennig Michael Markl Ute Ludwig 《Magnetic resonance in medicine》2010,63(5):1219-1229
Time‐of‐flight (TOF) MR angiography allows for noninvasive vessel imaging. To overcome the limited volumetric coverage of standard TOF techniques, the aim of this study was to investigate the combination of TOF and continuously moving table (CMT) acquisitions for peripheral vein imaging based on image subtraction. Two acquisition strategies are presented: a simple two‐step method based on 2‐fold CMT acquisition and an advanced one‐step method requiring only one continuous scan. Image quality of both CMT TOF techniques was evaluated by semiquantitative image grading and by signal‐to‐noise ratio and contrast‐to‐noise ratio analysis for veins of the upper and lower leg in 10 healthy volunteers. Results were compared to a standard stationary two‐dimensional (2D) TOF multistation acquisition. Image grading revealed good image quality for both CMT TOF methods, thereby confirming the feasibility of axial 2D CMT TOF to assess the veins of the lower extremities during a single scan. Quantitative evaluation showed no significant difference in signal‐to‐noise ratio and contrast‐to‐noise ratio compared to the stationary experiment. Additional measurements in three patients with postthrombotic changes and varicosities demonstrated the clinical applicability of the presented methods. CMT TOF provides promising results and permits the detection of various pathologic changes of the venous system. Magn Reson Med 63:1219–1229, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
103.
Dreses-Werringloer U Bhuiyan M Zhao Y Gérard HC Whittum-Hudson JA Hudson AP 《International journal of medical microbiology : IJMM》2009,299(3):187-201
Previous studies from this laboratory provided evidence that the intracellular bacterial pathogen Chlamydophila (Chlamydia) pneumoniae is present in the late-onset Alzheimer's disease (AD) brain. Here we report culture of the organism from two AD brain samples, each of which originated from a different geographic region of North America. Culturable organisms were detectable after one and two passages in HEp-2 cells for the two samples. Both isolates, designated Tor-1 and Phi-1, were demonstrated to be authentic C. pneumoniae using PCR assays targeting the C. pneumoniae-specific genes Cpn0695, Cpn1046, and tyrP. Assessment of inclusion morphology and quantitation of infectious yields in epithelial (HEp-2), astrocytic (U-87 MG), and microglial (CHME-5) cell lines demonstrated an active, rather than a persistent, growth phenotype for both isolates in all host cell types. Sequencing of the omp1 gene from each isolate, and directly from DNA prepared from several additional AD brain tissue samples PCR-positive for C. pneumoniae, revealed genetically diverse chlamydial populations. Both brain isolates carry several copies of the tyrP gene, a triple copy in Tor-1, and predominantly a triple copy in Phi-1 with a minor population component having a double copy. This observation indicated that the brain isolates are more closely related to respiratory than to vascular/atheroma strains of C. pneumoniae. 相似文献
104.
Anne-Marie Demers Amour Venter Sven O. Friedrich Gabriel Rojas-Ponce Daniel Mapamba Levan Jugheli Mohammed Sasamalo Deepak Almeida Afton Dorasamy Ute Jentsch Mara Gibson Daniel Everitt Kathleen D. Eisenach Andreas H. Diacon 《Journal of clinical microbiology》2016,54(5):1276-1281
Pyrazinamide (PZA) is a key antituberculosis drug, yet no rapid susceptibility test is commercially available. PZA drug susceptibility testing (DST) was performed directly on sputum samples from 327 patients and compared with the indirect method by using the Bactec MGIT 960 system in the context of patient screening for participation in a drug trial. Compared to standard indirect PZA DST, direct DST was successful in only 59% of cases, but results obtained were highly accurate and available faster. Agreement between the direct and indirect methods varied from 90 to 100% in each laboratory. The median times for obtaining PZA results from the time when the specimen was collected ranged from 11 to 16 days for the direct test and 18 to 95 days for the indirect test across laboratories. The direct method is accurate and reproducible across laboratories. It can be expected to accelerate results in >50% of cases, but it cannot replace indirect DST for PZA. Phenotypic methods remain the gold standard for DST in drug trials. If future studies can optimize the method to decrease the number of uninterpretable results, direct MGIT DST could be the new phenotypic DST standard for clinical trials, providing more rapid detection of resistance to new drugs in experimental regimens. 相似文献
105.
High Frequency of Pathogenic Rearrangements in SPG11 and Extensive Contribution of Mutational Hotspots and Founder Alleles 下载免费PDF全文
Sven Günther Ewelina Elert‐Dobkowska Anne S. Soehn Sophie Hinreiner Grace Yoon Raoul Heller Yorck Hellenbroich Christian A. Hübner Peter N. Ray Ute Hehr Peter Bauer Anna Sulek Christian Beetz 《Human mutation》2016,37(7):703-709
Biallelic loss‐of‐function mutations in SPG11 cause a wide spectrum of recessively inherited, neurodegenerative disorders including hereditary spastic paraplegia (HSP), amyotrophic lateral sclerosis, and Charcot‐Marie‐Tooth disease. By comprehensive screening of three large cohorts of HSP index patients, we identified 83 alleles with “small” mutations and 13 alleles that carry large genomic rearrangements. Including relevant data from previous studies, we estimate that copy number variants (CNVs) account for ~19% of pathogenic SPG11 alleles. The breakpoints for all novel and some previously reported CNVs were determined by long‐range PCR and sequencing. This revealed several Alu‐associated recombination hotspots. We also found evidence for additional mutational mechanisms, including for a two‐step event in which an Alu retrotransposition preceded the actual rearrangement. Apparently independent samples with identical breakpoints were analyzed by microsatellite PCRs. The resulting haplotypes suggested the existence of two rearrangement founder alleles. Our findings widen the spectra of mutations and mutational mechanisms in SPG11, underscore the pivotal role played by Alus, and are of high diagnostic relevance for a wide spectrum of clinical phenotypes including the most frequent form of recessive HSP. 相似文献
106.
Peter Schmidt Christa Kühn Jean-Charles Maillard Christian Pitra Ute Tiemann Rosemarie Weikard Manfred Schwerin 《Journal of interferon & cytokine research》2002,22(9):923-934
This study aimed to identify interferon-gamma (IFN-gamma) gene variants in cattle for diagnostic purposes. Therefore, the entire bovine IFN-gamma gene (BoIFNG) and 2605 bp of its promoter DNA were sequenced. The BoIFNG DNA sequence conforms to the published part of Bo-IFN-gamma cDNA. Primer extension experiments show the presence of a 5' extension of exon 1 by 42 nucleotides (nt). One SINE element (Bov-A2) is located in the 5'-region, and two SINE elements (Bov-tA, Bov-B) are contained in the 3'-region of BoIFNG. The variants were detected by comparative sequence analysis of PCR amplicons from different bovine species. Four polymorphic mononucleotide repeats are situated in the promoter and in intron 1. Four distinct series of single nucleotide polymorphisms (SNP) were found in functionally important regions of BoIFNG. The region between the two intron 1 microsatellites contains the highest density of SNPs in Bos taurus breeds. One G-T transversion in the coding region of exon 1 causes a Gly(14) to Val(14) exchange in the BoIFNG signal peptide of different bovine species. A G-A transition in exon 2 encodes a Ser(19) to Asn(19) change in the mature protein of the Tibetan yak. Genotyping of randomly sampled Holstein Friesian cows at selected SNPs and of both intron 1 microsatellites revealed two dominant BoIFNG microhaplotypes. The detected SNPs improve the recently reported genotyping system of cattle. 相似文献
107.
108.
Molecular cloning of a vaccine antigen against infection with the larval stage of Echinococcus multilocularis 下载免费PDF全文
Gauci C Merli M Muller V Chow C Yagi K Mackenstedt U Lightowlers MW 《Infection and immunity》2002,70(7):3969-3972
Alveolar and cystic hydatidosis are caused by infection with the larval stages of Echinococcus multilocularis and Echinococcus granulosus, respectively. A host-protective antigen has been identified in E. granulosus. Here we identify the presence of a closely related protein in E. multilocularis, characterize and express a cDNA encoding the antigen (designated EM95), determine the structure of the em95 gene, and demonstrate that the EM95 recombinant protein can be used to induce significant levels of protection against challenge infection with E. multilocularis eggs in mice. 相似文献
109.
Cathryn J. Poulton Rachel Schot Katja Seufert Maarten H. Lequin Andrea Accogli Giuseppe D' Annunzio Laurent Villard Nicole Philip René de Coo Coriene Catsman‐Berrevoets Ute Grasshoff Anja Kattentidt‐Mouravieva Hans Calf Erika de Vreugt‐Gronloh Leontine van Unen Frans W. Verheijen Niels Galjart Deborah J. Morris‐Rosendahl Grazia M. S. Mancini 《American journal of medical genetics. Part A》2014,164(9):2161-2171
110.
Urs-Vito Albrecht Ute von Jan Joachim Kuebler Christoph Zoeller Martin Lacher Oliver J Muensterer Max Ettinger Michael Klintschar Lars Hagemeier 《Journal of medical Internet research》2014,16(2)