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  • 1
    Abstract: Psoriasis vulgaris is a common T cell-mediated inflammatory skin disease with a suspected autoimmune pathogenesis. The human leukocyte antigen (HLA) class I allele, HLA-C*06:02, is the main psoriasis risk gene. Epidermal CD8(+) T cells are essential for psoriasis development. Functional implications of HLA-C*06:02 and mechanisms of lesional T cell activation in psoriasis, however, remained elusive. Here we identify melanocytes as skin-specific target cells of an HLA-C*06:02-restricted psoriatic T cell response. We found that a Valpha3S1/Vbeta13S1 T cell receptor (TCR), which we had reconstituted from an epidermal CD8(+) T cell clone of an HLA-C*06:02-positive psoriasis patient specifically recognizes HLA-C*06:02-positive melanocytes. Through peptide library screening, we identified ADAMTS-like protein 5 (ADAMTSL5) as an HLA-C*06:02-presented melanocytic autoantigen of the Valpha3S1/Vbeta13S1 TCR. Consistent with the Valpha3S1/Vbeta13S1-TCR reactivity, we observed numerous CD8(+) T cells in psoriasis lesions attacking melanocytes, the only epidermal cells expressing ADAMTSL5. Furthermore, ADAMTSL5 stimulation induced the psoriasis signature cytokine, IL-17A, in CD8(+) T cells from psoriasis patients only, supporting a role as psoriatic autoantigen. This unbiased analysis of a TCR obtained directly from tissue-infiltrating CD8(+) T cells reveals that in psoriasis HLA-C*06:02 directs an autoimmune response against melanocytes through autoantigen presentation. We propose that HLA-C*06:02 may predispose to psoriasis via this newly identified autoimmune pathway.
    Type of Publication: Journal article published
    PubMed ID: 26621454
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  • 2
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Cytogenetic and molecular genetic findings in 91 patients with Turner syndrome are reported. In 87 patients, chromosome studies were carried out both in lymphocyte and fibroblast cultures. Mosaicism was demonstrated in 58 of these patients (66.7%), whereas only 18 (20.7%) were apparent non-mosaic 45,X, and 11 patients (12.6%) showed non-mosaic structural aberrations of the X chromosome. Among the mosaic cases 16 (18.4% of all patients) displayed a second cell line containing small marker chromosomes. The association of Y-specific chromosomal material with the presence of marker chromosomes was demonstrated in 6 out of 7 mixoploid fibroblast cell lines by polymerase chain reaction amplification and by Southern-blot analysis. The observation of ring formation and morphological variability in vivo and in vitro, and the continous reduction in the percentage of cells containing marker chromosomes in longterm cultivation experiments indicated an increased instability of marker chromosomes. The findings suggest that in vivo selection of structurally altered sex chromosomes exists. Thus, the observation of apparent non-mosaic 45,X chromosomal complements in liveborn individuals with Turner syndrome does not contradict the hypothesis that some degree of mosaicism is necessary for survival in early pregnancy.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung 1. Der Vergleich der tryptischen Peptide von normaler und dibucain-resistenter Pseudocholinesterase zeigte eine unterschiedliche elektrophoretische Beweglichkeit für die mit radioaktivem DFP markierbaren Peptide. Die Ergebnisse ließen auf den Verlust einer negativen Ladung in der Nähe der esteratischen Stelle des aktiven Zentrums bei der Enzymvariante schließen. 2. Die quantitative Untersuchung der interindividuellen Variabilität des Pseudocholinesteraseantigens und der Enzymaktivität in einer Stichprobe der Bevölkerung ergab eine enge Korrelation der Werte. Seren, die die C5-Variante enthielten, hatten mehr Pseudocholinesteraseantigen als C5-negative Seren. Die Möglichkeit der Erkennung subtoxischer Insecticidbelastungen wurde aufgezeigt. 3. Immunologische und biochemische Untersuchungen an kultivierten menschlichen Fibroblasten von normalen und enzymdefizienten Individuen ergaben keine Evidenz für die Synthese von Pseudocholinesterase.
    Notes: Summary 1. The comparison of the tryptic peptides of usual and dibucain-resistent Pseudocholinesterase revealed a different electrophoretic mobility of those peptides which can be labelled with radioactive DFP. The results suggested the loss of a negative charge near the esteratic site of the active center in the variant enzyme. 2. The investigation of quantitative interindividual variation of Pseudocholinesterase antigen and enzyme activity in a sample of the population showed a high correlation of the values. Sera containing the C5-variant have more antigen than C5-negative sera. A possibility to detect subtoxic exposure to organophosphates was pointed out. 3. Immunological and biochemical investigations on human cultured fibroblasts from normal and enzyme deficient individuals failed to give evidence for the synthesis of Pseudocholinesterase.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1076
    Keywords: Farber disease ; Lipogranulomatosis ; Acid ceramidase deficiency ; Arthropathy ; Hoarseness ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 20-month-old girl showed typical clinical signs of Farber disease: hoarseness since birth, and periarticular subcutaneous painful nodules. Complete deficiency of acid ceramidase activity was found in cultured skin fibroblasts. An electron microscopic examination of a dermal nodule disclosed pathognomonic tubular inclusions in histiocytes. In epidermal cells zebra-body-like and needle-like lysosomal inclusions were found. Their ultrastructure is different from that of the intrahistiocytic lysosomal inclusions. Probably three clinical types of Farber disease may be distinguished according to the symptomatology and the course of the discase: a severe type, an intermediate type and a relatively mild type. The activity of acid ceramidase does not correlate with prognosis of the disease, while a correlation between first appearance of dermal nodules and clinical course appears likely.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0584
    Keywords: Chronic myelogenous leukemia ; Trisomy 8 ; Trisomy 8 mosaicism syndrome ; Constitutional disorders
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 17-year-old woman was admitted for bone marrow transplantation with the diagnosis of atypical Philadelphia-negative chronic myelogenous leukemia (aCML), cytogenetically characterized by trisomy 8 as the sole chromosome aberration. A striking feature was a congenital opacity of the right cornea. Chromosomal analysis of skin fibroblasts were performed and revealed a mosaic for trisomy 8. Commonly, a distinct clinical picture leads to the diagnosis of trisomy 8 mosaicism syndrome (T8ms), but an extreme phenotypic variability has been observed. To our knowledge the development of an aCML in a patient with T8ms has not been reported. A review of the literature revealed that an association to other hematological disorders had been described in two cases. The question of whether our patient's aCML was a random event or not is discussed. The patient is now 24 months post transplant and shows no evidence of disease. Her Karnofsky score is 100%. We conclude that it might be worthwhile to look for an associated constitutional trisomy 8 mosaicism in all patients with trisomy 8 leukemia.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1434-6036
    Keywords: PACS. 71.27.+a Strongly correlated electron systems; heavy fermions - 75.10.Lp Band and itinerant models - 75.30.Kz Magnetic phase boundaries
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract: The importance of Hund's rule coupling for the stabilization of itinerant ferromagnetism is investigated within a two-band Hubbard model. The magnetic phase diagram is calculated by finite-temperature quantum Monte-Carlo simulations within the dynamical mean-field theory. Ferromagnetism is found in a broad range of electron fillings whereas antiferromagnetism exists only near half filling. The possibility of orbital ordering at quarter filling is also analyzed.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1434-6036
    Keywords: PACS. 71.27.+a Strongly correlated electron systems; heavy fermions - 71.10.Fd Lattice fermion models (Hubbard model, etc.) - 71.30.+h Metal-insulator transitions and other electronic transitions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract: We show analytically that, under certain assumptions, the periodic Anderson model and the Hubbard model become equivalent within the dynamical mean field theory for quasiparticle weight . A scaling relation is derived which is validated numerically using the numerical renormalization group at zero temperature and quantum Monte Carlo simulations at finite temperatures. Our results show that the f-electrons of the half-filled periodic Anderson model with nearest neighbor hybridization get localized at a finite critical interaction strength , also at zero temperature. This transition is equivalent to the Mott-transition in the Hubbard model.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1434-6036
    Keywords: PACS. 71.27.+a Strongly correlated electron systems; heavy fermions - 74.25.Jb Electronic structure - 79.60.-i Photoemission and photoelectron spectra
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract: The spectral properties of La1–xSrxTiO3, a doped Mott insulator with strong Coulomb correlations, are calculated with the ab initio computational scheme LDA+DMFT(QMC). It starts from the non-interacting electronic band structure as calculated by the local density approximation (LDA), and introduces the missing correlations by the dynamical mean-field theory (DMFT), using numerically exact quantum Monte-Carlo (QMC) techniques to solve the resulting self-consistent multi-band single-impurity problem. The results of the LDA+DMFT(QMC) approach for the photoemission spectra of La1–xSrxTiO3 are in good agreement with experiment and represent a considerable qualitative and quantitative improvement on standard LDA calculations.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Analytical chemistry 23 (1951), S. 620-622 
    ISSN: 1520-6882
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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