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Background: TREATgermany, a registry for patients with moderate to severe atopic dermatitis (AD), established an additional questionnaire in spring 2020 to investigate the effects of the coronavirus pandemic on the daily life of patients with AD., Material and Methods: A questionnaire was used to analyze general information regarding a patient's experience of the coronavirus pandemic and, using the Inventory of Life-Changing Events, the resulting personal burden. To analyze possible associations between disease severity (EASI score, oSCORAD, IGA, PGA, POEM), quality of life (DLQI) and personal burden, t-tests, analyses of variance and correlations were evaluated, controlled for sex and age., Results: 58 % (n = 233) of the included 400 registry patients reported high burden scores caused by the coronavirus pandemic, regardless of an actual infection. Men showed significantly higher burden scores than women, and younger than older respondents (both P = 0.03). There were no differences in burden scores related to the physician's assessment of disease severity. However, patients with higher quality of life impairments and higher disease severity perceived the burden of the coronavirus pandemic as less severe (DLQI P = 0.019, PGA P = 0.044)., Conclusions: Our data show that registry patients considered the coronavirus pandemic as a life-changing event and perceived the burden differently. This should be taken into account in the treatment of patients with moderate to severe AD as well as in further studies., (© 2021 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Background: The Atopic Dermatitis (AD) TREATgermany registry was initiated by the German Society for Dermatology (DDG) in 2011 to evaluate the 'real-life' situation of health care for patients with AD., Objectives: Interim data analysis on baseline characteristics as well as current and prescribed systemic treatments of the TREATgermany registry patients., Methods: Patients (≥18 years) with moderate-to-severe AD [objective (o)SCORAD > 20], or with current or previous anti-inflammatory systemic treatment for AD within 24 months, were included and are followed up over at least 24 months. To assess clinical signs, the eczema area severity index (EASI, 0-72), the oSCORAD (0-83) and the Investigator Global Assessment (IGA; 6-point scale) were used. The disease severity was globally scored by the patients [Patient Global Assessment (PGA); six-step Likert scale]. Disease symptoms were assessed by the patient-oriented eczema measure (POEM, 0-28) and numeric rating scales (NRS, 0-10). Health-related quality of life was measured using the dermatological life quality index (DLQI, 0-30)., Results: A total of 612 patients were recruited across 32 sites between 06/2016 and 01/2019 (mean age: 42.6 ± 14.2 years; mean oSCORAD: 40.8 ± 16.3). The mean POEM score was 16.3 ± 7.5. Pruritus was rated highest among subjective symptoms (NRS: 5.4 ± 2.7). The mean DLQI value was 11.3 ± 7.5. The frequency of arterial hypertension was lower (20.8%) compared with the general population, whilst this was higher for depression (10%). More than 60% of the patients had received systemic glucocorticosteroids, and 36.8% had received cyclosporine A prior to inclusion. Dupilumab was the leading substance documented as either 'current' (12.1%) or 'prescribed' (31.4%) at baseline., Conclusions: These 'real-life' data clearly demonstrate the substantial disease burden. Most of TREATgermany patients were already treated with or prescribed dupilumab at baseline. Moreover, current findings indicate the urgent need for further alternative agents in order to achieve a perceptible improvement of quality of life of patients with moderate-to-severe AD., (© 2019 European Academy of Dermatology and Venereology.)

Individuals born with a low birth weight (LBW) have an increased prevalence of type 2 diabetes, but the mechanisms responsible for this association are unknown. Given the important role of insulin resistance in the pathogenesis of type 2 diabetes, we examined insulin sensitivity in a rat model of LBW due to intrauterine fetal stress. During the last 7 days of gestation, rat dams were treated with dexamethasone and insulin sensitivity was assessed in the LBW offspring by a hyperinsulinemic euglycemic clamp. The LBW group had liver-specific insulin resistance associated with increased levels of PEPCK expression. These changes were associated with pituitary hyperplasia of the ACTH-secreting cells, increased morning plasma ACTH concentrations, elevated corticosterone secretion during restraint stress, and an approximately 70% increase in 24-h urine corticosterone excretion. These data support the hypothesis that prenatal stress can result in chronic hyperactivity of the hypothalamic-pituitary-adrenal axis, resulting in increased plasma corticosterone concentrations, upregulation of hepatic gluconeogenesis, and hepatic insulin resistance.

Mice lacking C3, C4 or complement receptor 1/2 (Cr) have defective germinal centers (GC). The requirement for C4 implicates complement fixation by immune complexes (IC) via the classical pathway. Yet, transgenic (Tg) mice that lack circulating antibody but still express membrane IgM (mIgM) have normal GC responses. We showed previously that cross-linking mIgM leads to the deposition of C3 on the B cell surface and that disruption of this pathway diminishes GC responses. Here, we investigate the role of Cr in this process by generating mIgM-Tg mice that lack Cr and serum Ig. These mIgM/Cr-/- mice have smaller, transient GC, with incomplete B cell receptor down-regulation and peanut agglutinin up-regulation, compared to mIgM/Crwt counterparts. BM chimera experiments showed that Cr on B cells is required for normal GC responses. These results establish that Cr ligands generated at the B cell surface are sufficient for normal GC responses and function by signaling Cr on B cells. Unexpectedly, chimera experiments also showed a critical role for Cr on follicular dendritic cells (FDC), even in the absence of IC, indicating novel functions for FDC-expressed Cr beyond the capture of C3-coated IC.

RUVBL1/TIP49a/Pontin52 is a recently identified multi-functional protein with 2 ATP binding (WALKER) sites, which is essential for cell proliferation. We recovered and identified RUVBL1/TIP49a as a tubulin-binding protein from Triton X-100 lysates of U937 promonocytic cells by protein affinity chromatography and tryptic peptide microsequencing. Performing co-immunoprecipitation using newly generated RUVBL1/TIP49a-specific antibodies (mAb and rabbit polyclonal Ab) and RUVBL1/TIP49a-GST fusion protein-pull down assays we demonstrate co-precipitation of alpha- and gamma tubulin with RUVBL1/TIP49a. Confocal immunoflourescence microscopy reveals that RUVBL1/TIP49a was present not only in the nucleus, as expected, but was also concentrated at the centrosome and at the mitotic spindle in colocalization with tubulin. The topology of RUVBL1/TIP49a at the mitotic spindle varied, depending on the mitotic stage. The protein was localized at the centrosome and at the polar and astral microtubules in metaphase, and was detectable at the zone of polar tubule interdigitation in anaphase B and telophase. During cytokinesis the protein reappeared at the area of decondensing chromosomes. Whereas preincubation of U937 cells with colcemid resulted in inhibition of mitotic spindle formation with subsequent loss of RUVBL1/TIP49a mitotic spindle staining, no relevant influence of colcemid on RUVBL1/TIP49a-tubulin binding was observed. An agonistic effect of RUVBL1/TIP49a on in vitro tubulin assembly is demonstrated. Our results reveal a new functional aspect of RUVBL1/TIP49a., (Copyright 2003 Wiley-Liss, Inc.)

B cells express complement receptors (CRs) that bind activated fragments of C3 and C4. Immunized CR knockout (KO) mice have lower antibody titers and smaller germinal centers (GCs), demonstrating the importance of CR signals for the humoral immune response. CR ligands were thought to be generated via complement fixation mediated by preexisting "natural" IgM or early Ab from inefficiently activated B cells. This concept was recently challenged by a transgenic (Tg) mouse model that lacks circulating antibody but still retains membrane IgM (mIgM) and mounts normal immune responses. To test whether CR ligands could be generated by the B cell receptor (BCR) itself, we generated similar mice carrying a mutated mIgM that was defective in C1q binding. We found that B cells from such mutant mice do not deposit C3 on B cells upon BCR ligation, in contrast to B cells from mIgM mice. This has implications for the immune response: the mutant mice have smaller GCs than mIgM mice, and they are particularly deficient in the maintenance of the GC response. These results demonstrate a new BCR-dependent pathway that is sufficient and perhaps necessary to provide a CR1/2 ligand that promotes efficient B cell activation.