Interferon-γ Decreases Ceramides with Long-Chain Fatty Acids: Possible Involvement in Atopic Dermatitis and Psoriasis

Ceramide (CER) with long-chain fatty acids (FAs) in the human stratum corneum (SC) is important for the skin barrier functions. Changes in the CER profile have been associated with abnormal permeability of dermatoses such as atopic dermatitis (AD) and psoriasis. In addition, interferon-γ (IFN-γ) has been known to be abundant in both AD and psoriatic skin lesions. In this study, we aimed to identify the mechanism underlying the alteration of FA chain length of CERs in these diseases. Mass spectrometry analysis of CERs in the SC showed that the proportion of CERs with long-chain FAs was significantly lower in AD and psoriasis patients than in healthy controls, and this reduction was more pronounced in psoriasis than in AD. Using cultured human keratinocytes and epidermal sheets, we found that only IFN-γ among various cytokines decreased the mRNA expression of elongase of long-chain fatty acids (ELOVL) and ceramide synthase (CerS), enzymes involved in FA chain elongation. Furthermore, quantitative analysis showed that IFN-γ decreased the levels of CERs with long-chain FAs. These results suggest that IFN-γ decreases CERs with long-chain FAs through the downregulation of ELOVL and CerS and that this mechanism may be involved in the CER profile alteration observed in psoriasis and AD

A case of VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) with decreased oxidative stress levels after oral prednisone and tocilizumab treatment

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome has recently been described as an autoinflammatory disease associated with severe adult-onset inflammatory manifestations. The various clinical manifestations include recurrent high-grade fever, neutrophilic dermatoses, cutaneous vasculitis, chondritis of the ear and nose, pulmonary infiltrates, cytopenia, uveitis, gastrointestinal pain or inflammation, aortitis, hepatosplenomegaly, and hematological disorders. VEXAS syndrome is caused by somatic mutations of the ubiquitin-like modifier activating enzyme 1 (UBA1) gene in myeloid-lineage cells. It is characterized by vacuolated myeloid and erythroid progenitor cells seen by bone marrow biopsy. We report the case of a 64-year-old Japanese man with VEXAS syndrome. At age 63, he was referred to us with a recurrent erythema on the hands associated with a general fever of 38–40°C that had persisted for 4 or 5 days and had recurred about once a month for a year. The skin rash appeared 2 or 3 days after the onset of each fever episode. Computed tomography (CT) of the chest revealed bilateral hilar lymphadenopathy (BHL), and the mediastinal lymph nodes were swollen. Sarcoidosis was suspected but was ruled out by several tests. Laboratory examinations showed elevated inflammatory markers. Bone marrow examination showed the vacuolization of myeloid precursor cells. A skin biopsy revealed dense dermal, predominantly perivascular, infiltrates. These consisted of mature neutrophils admixed with myeloperoxidase-positive CD163-positive myeloid cells, lymphoid cells and eosinophils. Sequencing analysis identified the somatic UBA1 variant c.122T > C, which results in p.Met41Thr. Treatment with oral prednisone (15 mg/day) and monthly intravenous tocilizumab injections (400 mg) completely resolved the symptoms. Neutrophils are a major source of reactive oxygen species, and the present case demonstrated numerous neutrophilic infiltrates. We hypothesize that the patient might have had elevated derivatives of reactive oxygen metabolites (d-ROMs). d-ROM quantification is a simple method for detecting hydroperoxide levels, and clinical trials have proven it useful for evaluating oxidative stress. In this study, we measured serum d-ROM before and after oral prednisone and tocilizumab treatment. The levels decreased significantly during treatment

Ariadnefäden als Harfensaiten des Denkens

Neulich nahm ich ein Buch von Sigrid Weigel in die Hand, das 1982 erschienen ist. Normalerweise bleiben alle Buchtitel auf einer Publikationsliste brav in einer chronologischen Reihe, und selbst wenn die Schlange sehr lang ist, was bei Weigel zweifellos der Fall ist, springt keiner von ihnen aus der Reihe und rennt nach vorne, in Richtung Zukunft. Aber es kommt doch vor, dass man, zum Beispiel bei einem Umzug, eines der Frühwerke in die Hand nimmt und darin blättert. Man wird überrascht von schillernden Denkbildern, die von heute sein könnten. Ansätze und Zusammenhänge, die man einer späteren Phase zugeordnet hätte, oder solche, die man jetzt erst begreift, stehen bereits in den älteren Büchern schwarz auf weiß. Gerade im digitalen Zeitalter, in dem die historischen Rahmen verschwimmen, gefällt mir die Unbestechlichkeit des Papiers, das die Zeit nie schleichend verfälscht. In der Forschung gibt es stets Fortschritt, aber wenn ich mir erlaube, Weigels Schriften nicht nur als wissenschaftliche Texte, sondern als Texte in ihrer gattungsfreien Nacktheit zu lesen, gibt es keinen Satz darin, der überholt ist. Die zeitliche Ordnung bleibt, verliert aber ihren hierarchischen Charakter. Wo ich eine alte Erinnerung erwarte, entdecke ich eine neue Möglichkeit, die Gegenwart zu verstehen. So entstand in mir der Wunsch, die jüngere Vergangenheit durch das Fenster der älteren zu betrachten. Ich rede hier nicht von der magischen Glaskugel einer Wahrsagerin, sondern von einer soliden Relektüre

Memorie di un’orsa polare Etüden im Schnee

Yoko Tawada è una delle voci più significative e originali del panorama letterario contemporaneo. Nata in Giappone nel 1960, residente a Berlino, scrive sia in tedesco sia in giapponese, intrecciando nella sua scrittura lingue, mondi, codici. Attraversando la poesia, la narrativa, breve, il romanzo, Yoko Tawada offre una delle più singolari esperienze di lettura, capace di spiazzare e allo stesso tempo coinvolgere nel proprio mondo finzionale. Proprio per questo, l’occasione di ascoltarla dal vivo ha coinciso con la chiusura del progetto. In collaborazione con e con il sostegno di Goethe Institut - Roma e DAADGoethe Institut - RomaDAA