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101.
Schmits R Kubuschok B Schuster S Preuss KD Pfreundschuh M 《Clinical and experimental immunology》2002,127(2):379-385
The analysis of the antibody repertoire of patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) might identify target antigens of the autoimmune response with potential relevance to our understanding of the pathogenesis of the disease and to the development of serodiagnostic tests. To detect such antigens, we screened a cDNA library derived from normal human testis for antigens reacting with IgG antibodies in the 1 : 250 diluted sera of three patients with untreated GCA using SEREX, the serological identification of antigens by recombinant cDNA expression cloning. Of 100 000 clones screened with each serum, six, 28 and six clones, respectively, were positive, representing a total of 33 different antigens. Most of the antigens reacted only with the serum used for identification and/or at a similar frequency with normal control sera. However, lamin C and the nuclear antigen of 14 kD reacted specifically with 32% of GCA/PMR, but with none of the control sera, while human cytokeratin 15, mitochondrial cytochrome oxidase subunit II, and a new gene product were detected preferentially, but not exclusively by sera from GCA/PMR patients. We conclude that patients with GCA/PMR develop antibodies against a broad spectrum of human autoantigens. Antibodies against human lamin C, the nuclear autoantigen of 14 kD as well as human cytokeratin 15, mitochondrial cytochrome oxidase subunit II and the product of a new gene should be investigated further to determine their value as tools for the diagnosis and/or the definition of clinical subgroups of patients with GCA/PMR. 相似文献
102.
Henrik Wilms Jobst Sievers Uta Rickert Martin Rostami-Yazdi Ulrich Mrowietz Ralph Lucius 《Journal of neuroinflammation》2010,7(1):30
Background
Brain inflammation plays a central role in multiple sclerosis (MS). Dimethylfumarate (DMF), the main ingredient of an oral formulation of fumaric acid esters with proven therapeutic efficacy in psoriasis, has recently been found to ameliorate the course of relapsing-remitting MS. Glial cells are the effector cells of neuroinflammation; however, little is known of the effect of DMF on microglia and astrocytes. The purpose of this study was to use an established in vitro model of brain inflammation to determine if DMF modulates the release of neurotoxic molecules from microglia and astrocytes, thus inhibiting glial inflammation. 相似文献103.
Mutational analysis using Sanger and next generation sequencing in sporadic spindle cell hemangiomas: A study of 19 cases 下载免费PDF全文
Roel W. ten Broek Elise M. Bekers Wendy W. J. de Leng Eric Strengman Bastiaan B. J. Tops Heinz Kutzner Jan Willem Leeuwis Joost M. van Gorp David H. Creytens Thomas Mentzel Paul J. van Diest Astrid Eijkelenboom Uta Flucke 《Genes, chromosomes & cancer》2017,56(12):855-860
Spindle cell hemangioma (SCH) is a distinct vascular soft ‐ tissue lesion characterized by cavernous blood vessels and a spindle cell component mainly occurring in the distal extremities of young adults. The majority of cases harbor heterozygous mutations in IDH1/2 sporadically or rarely in association with Maffucci syndrome. However, based on mosaicism and accordingly a low percentage of lesional cells harboring a mutant allele, detection can be challenging. We tested 19 sporadic SCHs by Sanger sequencing, multiplex ligation‐dependent probe amplification (MLPA), conventional next generation sequencing (NGS), and NGS using a single molecule molecular inversion probes (smMIP) ‐ based library preparation to compare their diagnostic value. Out of 10 cases tested by Sanger sequencing and 2 analyzed using MLPA, 4 and 1, respectively, revealed a mutation in IDH1 (p.R132C). The 7 remaining negative cases and additional 6 cases were investigated using smMIP/NGS, showing hot spot mutations in IDH1 (p.R132C) (8 cases) and IDH2 (3 cases; twice p.R172S and once p.R172G, respectively). One case was negative. Owing to insufficient DNA quality and insufficient coverage, 2 cases were excluded. In total, in 16 out of 17 cases successfully tested, an IDH1/2 mutation was found. Given that IDH1/2 mutations were absent in 161 other vascular lesions tested by smMIP/NGS, the mutation can be considered as highly specific for SCH. 相似文献
104.
BACKGROUND: We measured psychopathic traits in boys with autism spectrum disorder (ASD) selected for difficult and aggressive behaviour. We asked (i) whether psychopathic tendencies can be measured in ASD independent of the severity of autistic behaviour; (ii) whether individuals with ASD with callous-unemotional (CU) traits differ in their cognitive profile from those without such traits; and (iii) how the cognitive data from this study compare with previous data of youngsters with psychopathic tendencies. METHOD: Twenty-eight ASD boys were rated on psychopathic tendencies, autistic traits and a range of cognitive measures assessing mentalizing ability, executive functions, emotion recognition and ability to make moral-conventional distinction. RESULTS: Our results indicate that psychopathic tendencies are not related to severity of ASD. In addition, such tendencies do not seem to be related to core autistic cognitive deficits, specifically in 'mind-reading' or executive function. Boys with co-occurring ASD and CU tendencies share some behaviours and aspects of cognitive profile with boys who have psychopathic tendencies alone. CONCLUSIONS: Callous/psychopathic acts in a small number of individuals with ASD probably reflect a 'double hit' involving an additional impairment of empathic response to distress cues, which is not part and parcel of ASD itself. 相似文献
105.
Uta B. Hofmann Heike Voigt Mads H. Andersen Per thor Straten Jürgen C. Becker Andreas O. Eggert 《European journal of immunology》2009,39(5):1419-1424
Survivin is overexpressed in several malignancies and in tumor‐associated endothelium making it an attractive target for therapeutic cytotoxic T‐cell responses. Thus, it would be important to test this notion in preclinical models. Consequently, we screened the murine survivin sequence for potential binding Kb‐restricted octamer peptide epitopes. Two epitopes, which bind strongly to Kb, were selected to test their immunogenicity in vivo. Spleen cells from mice vaccinated by intradermal injection of mature DC pulsed with these peptides displayed reactivity to the respective epitopes. The natural processing and presentation of these epitopes by tumor cells was evident by the killing of murine melanoma cells by vaccination‐induced T cells. Subcutaneous challenge with syngeneic melanoma demonstrated the protective immunity of this vaccination. Notably, analysis of the vessel density in subcutaneous tumors revealed that survivin‐specific vaccination significantly reduced the number of intratumoral vessels. In summary, we demonstrated the immunogenicity of two Kb‐restricted peptide epitopes derived from the murine survivin protein; moreover, survivin‐specific vaccination not only resulted in a reduction of tumor cells but also the tumor supplying blood vessels. The presented preclinical model for survivin‐directed vaccination may serve as a valuable tool to improve already running clinical trials in a syngeneic tumor model. 相似文献
106.
Kretschmer U Bonhagen K Debes GF Mittrücker HW Erb KJ Liesenfeld O Zaiss D Kamradt T Syrbe U Hamann A 《European journal of immunology》2004,34(11):3070-3081
Endothelial selectins are crucial for the recruitment of leukocytes into sites of inflammation. On T cells, ligands for selectins become induced upon differentiation into the effector/memory stage. Initial in vitro studies suggested a correlation between the Th1 phenotype and ligand expression, but whether this also holds true in vivo remained uncertain. We here analyzed selectin ligands on CD4+ T cells producing IFN-gamma, IL-4 or IL-10, prototypic cytokines of the Th1, Th2 and Tr1 subset, respectively. We analyzed mice infected with influenza virus, the bacterium Listeria, and the parasites Toxoplasma (all Th1 models) or Nippostrongylus (Th2 model). A link between the Th1 phenotype and ligand expression was not found in vivo. Surprisingly, the potentially regulatory IL-10-producing T cells displayed the highest frequency of ligand-positive cells in general. Within the inflamed tissues, the frequencies of P-selectin-binding cells increased in the dominant subset, either Th1 or Th2. Up-regulation was also found for E-selectin ligands during influenza, but not Nippostrongylus infection. In conclusion, conditions driving T cell polarization into either Th1 or Th2 in vivo do not affect the expression of selectin ligands, but acquisition of P-selectin binding and hence migration into inflamed tissues is boosted by an inflammatory milieu. 相似文献
107.
Nissum M Preuss D Harig A Lieberwirth U Betz C Neumann S Deravanessian E Bock M Wehmeier L Bonk T 《Psychiatric genetics》2002,12(2):109-117
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has become a powerful and widespread analytical tool in all fields of life science. Compared with other techniques, its high accuracy and sensitivity makes it a superior method, especially for the analysis of nucleic acids. Recent problems in the analysis of nucleic acids by MALDI-TOF MS can be solved using an automated MALDI-compatible sample-preparation system. Together with the reliable minisequencing assay, high-throughput genotyping of single nucleotide polymorphisms by MALDI-TOF MS is able to become a routine method in research, clinical genetics and diagnostics. 相似文献
108.
Large-scale screening of nasal swabs for Bacillus anthracis: descriptive summary and discussion of the National Institutes of Health's experience 下载免费PDF全文
Kiratisin P Fukuda CD Wong A Stock F Preuss JC Ediger L Brahmbhatt TN Fischer SH Fedorko DP Witebsky FG Gill VJ 《Journal of clinical microbiology》2002,40(8):3012-3016
In October 2001, a letter containing a large number of anthrax spores was sent through the Brentwood post office in Washington, D.C., to a United States Senate office on Capitol Hill, resulting in contamination in both places. Several thousand people who worked at these sites were screened for spore exposure by collecting nasal swab samples. We describe here a screening protocol which we, as a level A laboratory, used on very short notice to process a large number of specimens (3,936 swabs) in order to report preliminary results as quickly as possible. Six isolates from our screening met preliminary criteria for Bacillus anthracis identification and were referred for definitive testing. Although none of the isolates was later confirmed to be B. anthracis, we studied these isolates further to define their biochemical characteristics and 16S rRNA sequences. Four of the six isolates were identified as Bacillus megaterium, one was identified as Bacillus cereus, and one was an unidentifiable Bacillus sp. Our results suggest that large-scale nasal-swab screening for potential exposure to anthrax spores, particularly if not done immediately postexposure, may not be very effective for detecting B. anthracis but may detect a number of Bacillus spp. that are phenotypically very similar to B. anthracis. 相似文献
109.
Sellner J Dvorak F Zhou Y Haas J Kehm R Wildemann B Meyding-Lamadè U 《Neuroscience letters》2005,374(3):197-202
Mortality and morbidity rates remain high among patients with herpes simplex virus encephalitis (HSVE). Chemokine-mediated recruitment and activation of leukocytes to focal areas of viral CNS infection are crucial steps in antiviral response and clearance. However, the inflammatory reaction and cellular antiviral response may enhance collateral damage to neurons and account for chronic progressive brain damage. We identified a specific mRNA expression of the interferon-gamma-inducible chemokines (CXCL9, CXCL10 and CXCL11), and RANTES (CCL5) in the acute course and long-term of experimental HSVE. This pattern was substantially altered by anti-viral and anti-inflammatory treatment. Our findings indicate a pivotal role of these chemokines in the immunopathogenesis of HSVE. 相似文献
110.
Edward?J?HolloxEmail author Jane?Davies Uta?Griesenbach Juliana?Burgess Eric?WFW?Alton John?AL?Armour 《Journal of negative results in biomedicine》2005,4(1):9
Human beta-defensin 2 (DEFB4, also known as DEFB2 or hBD-2) is a salt-sensitive antimicrobial protein that is expressed in
lung epithelia. Previous work has shown that it is encoded in a cluster of beta-defensin genes at 8p23.1, which varies in
copy number between 2 and 12 in different individuals. We determined the copy number of this locus in 355 patients with cystic
fibrosis (CF), and tested for correlation between beta-defensin cluster genomic copy number and lung disease associated with
CF. No significant association was found. 相似文献