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An excess of the proinflammatory substance IL-18 is present in joints of patients with rheumatoid arthritis (RA), and expression of IL-18 receptor (IL-18R) regulates IL-18 bioactivity in various cell types. We examined the expression of IL-18R alpha-chain and beta-chain and the biologic effects of IL-18 in fibroblast-like synoviocytes (FLS) after long-term culture. The presence of both IL-18R chains was a prerequisite for IL-18 signal transduction in FLS. However, all FLS cultures studied were either resistant or barely responsive to IL-18 stimulation as regards cell proliferation, expression of adhesion molecules ICAM-1 and vascular cell adhesion molecule (VCAM)-1, and the release of interstitial collagenase and stromelysin, IL-6 and IL-8, prostaglandin E2, or nitric oxide. We conclude that the presence of macrophages or IL-18R+ T cells that can respond directly to IL-18 is essential for the proinflammatory effects of IL-18 in synovitis in RA. Open Access: Published: 14 November 2001 © 2002 Möller et al., licensee BioMed Central Ltd (Print ISSN 1465-9905; Online ISSN 1465-9913)
Aus dem Kernteam des Punch von 1841 stammten der Journalist und Schriftsteller Gilbert Abbott à Beckett und John Leech, der eigentliche Erfinder des "Cartoons". In einer speziell englischen Spielart des komischen Genres schufen sie 1847/48 in 20 Einzelbänden "The Comic History of England". Joachim Möller zeigt unter dem Titel "Götterdämmerung", wie in engem Wechselspiel von Bild und Text die 'Großen Männer der Geschichte' gleich reihenweise vom Sockel gestoßen werden und sich ihre legendären Taten als 'ziemlich gewöhnlich' erweisen. Pate bei dieser Art detailverliebter Bildsatire hat offenbar immer noch Hogarth gestanden, auch wenn der Stahl- (und Holz-)stich in der "Comic History" die Funktion der interpretativen Illustration übernimmt.
Etwa 800 000 Bundesbürger leiden an rheumatoider Arthritis (RA), der häufigsten chronisch-entzündlichen Erkrankung der Gelenke. Obwohl die Forschung in den vergangenen Jahren erhebliche Fortschritte gemacht hat, sind die Ursachen dieser schmerzhaften, bisher unheilbaren Krankheit noch nicht im Einzelnen geklärt. In vielerlei Richtungen diskutiert wird eine Fehlsteuerung des Immunsystems, bei der körpereigene Gewebsmatrix, wie der Gelenkknorpel, von Zellen des Immunsystems angegriffen wird. Die Forschungen der Mediziner, auch der Frankfurter Gruppe, konzentrieren sich weltweit auf die entzündungsfördernden Faktoren, spezielle Zytokine, und die Hemmstoffe dieser Zytokine. Aus diesen Ansätzen resultieren die neuartigen "Biologics": gentechnisch hergestellte monoklonale Antikörper, die natürlich vorkommenden Wirkstoffen entsprechen. Sie richten sich spezifisch gegen bestimmte vom menschlichen Organismus gebildete Zytokine.
Pathogenic variants in PRRT2, encoding the proline-rich transmembrane protein 2, have been associated with an evolving spectrum of paroxysmal neurologic disorders. Based on a cohort of children with PRRT2-related infantile epilepsy, this study aimed at delineating the broad clinical spectrum of PRRT2-associated phenotypes in these children and their relatives. Only a few recent larger cohort studies are on record and findings from single reports were not confirmed so far. We collected detailed genetic and phenotypic data of 40 previously unreported patients from 36 families. All patients had benign infantile epilepsy and harbored pathogenic variants in PRRT2 (core cohort). Clinical data of 62 family members were included, comprising a cohort of 102 individuals (extended cohort) with PRRT2-associated neurological disease. Additional phenotypes in the cohort of patients with benign sporadic and familial infantile epilepsy consist of movement disorders with paroxysmal kinesigenic dyskinesia in six patients, infantile-onset movement disorders in 2 of 40 individuals, and episodic ataxia after mild head trauma in one girl with bi-allelic variants in PRRT2. The same girl displayed a focal cortical dysplasia upon brain imaging. Familial hemiplegic migraine and migraine with aura were reported in nine families. A single individual developed epilepsy with continuous spikes and waves during sleep. In addition to known variants, we report the novel variant c.843G>T, p.(Trp281Cys) that co-segregated with benign infantile epilepsy and migraine in one family. Our study highlights the variability of clinical presentations of patients harboring pathogenic PRRT2 variants and expands the associated phenotypic spectrum.