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31.
Astrid Rohrbeck Leonie von Elsner Sandra Hagemann Ingo Just 《Naunyn-Schmiedeberg's archives of pharmacology》2014,387(6):523-532
C3 from Clostridium botulinum (C3) specifically modifies Rho GTPases RhoA, RhoB, and RhoC by mono-ADP-ribosylation. The confined substrate profile of C3 is the basis for its use as pharmacological tool in cell biology to study cellular functions of Rho GTPases. Although C3 exoenzyme does not possess a cell-binding/-translocation domain, C3 is taken up by intact cells via an unknown mechanism. In the present work, binding of C3 to the hippocampus-derived HT22 cells and J774A.1 macrophages was characterized. C3 bound concentration-dependent to HT22 and J774A.1 cells. Pronase treatment of intact cells significantly reduced both C3 binding and C3 cell entry. Removal of sugar residues by glycosidase F treatment resulted in an increased binding of C3, but a reduced cell entry. To explore the involvement of phosphorylation in the binding process of C3, intact HT22 and J774A.1 cells were pre-treated with vanadate prior to incubation with C3. Inhibition of de-phosphorylation by vanadate resulted in an increased binding of C3. To differentiate between intracellular and extracellular phosphorylation, intact cells were treated with CIP (calf intestine phosphatase) to remove extracellular phosphate residues. The removal of phosphate residues resulted in a strong reduction in binding of C3 to cells. In sum, the C3 membranous binding partner is proteinaceous, and the glycosylation as well as the phosphorylation state is critical for efficient binding of C3. 相似文献
32.
The Clostridium botulinum C3 exoenzyme selectively ADP-ribosylates low molecular weight GTP-binding proteins RhoA, B and C. This covalent modification inhibits Rho signaling activity, resulting in distinct actin cytoskeleton changes. Although C3 exoenzyme has no binding, the translocation domain assures that C3 enters cells and acts intracellularly. C3 uptake is thought to occur due to the high concentration of the C3 enzyme. However, recent work indicates that C3 is selectively endocytosed, suggesting a specific endocytotic pathway, which is not yet understood. In this study, we show that the C3 exoenzyme binds to cell surfaces and is internalized in a time-dependent manner. We show that the intermediate filament, vimentin, is involved in C3 uptake, as indicated by the inhibition of C3 internalization by acrylamide, a known vimentin disruption agent. Inhibition of C3 internalization was not observed by chemical inhibitors, like bafilomycin A, methyl-β-cyclodextrin, nocodazole or latrunculin B. Furthermore, the internalization of C3 exoenzyme was markedly inhibited in dynasore-treated HT22 cells. Our results indicate that C3 internalization depends on vimentin and does not depend strictly on both clathrin and caveolae. 相似文献
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Incidence of lung cancer in patients with systemic sclerosis treated with extracorporeal photopheresis
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35.
Antonio Nieto Ulrich Wahn Albrecht Bufe Philippe Eigenmann Susanne Halken Gunilla Hedlin Arne Høst Jonathan Hourihane Jocelyne Just Gideon Lack Susanne Lau Paolo Maria Matricardi Antonella Muraro Nikos Papadopoulos Graham Roberts Angela Simpson Erkka Valovirta Stephan Weidinger Magnus Wickman Angel Mazon 《Pediatric allergy and immunology》2014,25(6):516-533
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New insights into the phenotypes of atopic dermatitis linked with allergies and asthma in children: An overview
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F. Amat A. Soria P. Tallon M. Bourgoin‐Heck N. Lambert A. Deschildre J. Just 《Clinical and experimental allergy》2018,48(8):919-934
Atopic dermatitis (AD) is a complex disease with multiple causes and complex mechanistic pathways according to age of onset, severity of the illness, ethnic modifiers, response to therapy and triggers. A group of difficult‐to‐manage patients characterized by early‐onset AD and severe lifelong disease associated with allergic asthma and/or food allergy (FA) has been identified. In this study, we focus on these severe phenotypes, analysing their links with other atopic comorbidities, and taking into account the results from recent cohort studies and meta‐analyses. The main hypothesis that is currently proposed to explain the onset of allergic diseases is an epithelial barrier defect. Thus, the atopic march could correspond to an epithelial dysfunction, self‐sustained by a secondary allergenic sensitization, explaining the transition from AD to allergic asthma. Furthermore, AD severity seems to be a risk factor for associated FA. Results from population‐based, birth and patient cohorts show that early‐onset and severe AD, male gender, parental history of asthma, and early and multiple sensitizations are risk factors leading to the atopic march and the development of asthma. The importance of environmental factors should be recognized in these high‐risk children and prevention programs adapted accordingly. Effective targeted therapies to restore both barrier function and to control inflammation are necessary; early emollient therapy is an important approach to prevent AD in high‐risk children. Clinicians should also keep in mind the specific risk of atopic comorbidities in case of filaggrin loss‐of‐function mutations and the rare phenotypes of orphan syndromes due to heritable mutations in skin barrier components. 相似文献
38.
H Drexler C Hirth-Dietrich J P Stasch D Neuser R Gross H U Kauczor H Just S Kazda 《Cardiovascular research》1991,25(7):558-564
STUDY OBJECTIVE--Plasma levels of atrial natriuretic factor are increased in chronic heart failure; however, it is still controversial whether these raised levels contribute to the diuresis and natriuresis in this setting. To address this issue the potential contribution of endogenous atrial natriuretic factor in the renal excretion of a moderate oral sodium load in a rat model of chronic heart failure was studied. DESIGN--A monoclonal antibody against atrial natriuretic factor was used for specific antagonisation of its in vivo effects. Animals were subjected to oral sodium loading (30 ml.kg-1 0.9% NaCl, 2.5% dextrose) at baseline, immediately after, and 5 d after injection of monoclonal antibody or control solvent. EXPERIMENTAL MATERIAL--Sham operated rats and rats with chronic heart failure due to myocardial infarction (infarct size 35(SEM 4)% of left ventricle) were studied 4-5 weeks after surgery. MEASUREMENTS AND MAIN RESULTS--The renal excretion of cyclic guanosine monophosphate (cGMP), which represents a specific marker for the activation of the atrial natriuretic factor system, was markedly increased in infarcted rats, at 17.9(SEM 3.4) vs 5.8(1.2) nmol.kg-1, p less than 0.01. Atrial natriuretic factor antibody given immediately before sodium loading reduced the natriuretic response (0-4 h period) in infarcted rats from 1270(171) to 805(76) mumol.kg-1 (p less than 0.01) but not in sham operated animals. Similarly, the excretion of cGMP was only decreased by atrial natriuretic factor antibody in infarcted rats, from 29.8(6.3) to 20.7(3.7) nmol.kg-1. The reduction in sodium and cGMP excretion in infarcted rats was confirmed with a purified antibody preparation. CONCLUSIONS--Endogenous atrial natriuretic factor appears to be involved in the natriuresis following a moderate oral volume load in chronic heart failure. Thus the raised concentrations found in chronic heart failure may contribute to the regulation of urinary sodium excretion under these conditions despite the fact that the diuretic effects of exogenous atrial natriuretic factor are attenuated in chronic heart failure. 相似文献
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Clinical and Doppler echocardiographic follow-up after percutaneous balloon valvuloplasty for aortic valve stenosis 总被引:1,自引:0,他引:1
Percutaneous balloon valvuloplasty has been shown to increase the aortic orifice area and to improve clinical symptoms. However, there are only few data concerning long-term results after balloon valvuloplasty. In this study, 36 patients (11 men, 25 women, mean age 75 +/- 8 years) were followed after balloon valvuloplasty for a period of up to 18 months by means of clinical parameters and repeated Doppler echocardiographic measurements after 1, 3, 6, 12 and 18 months. Invasive measurements revealed a decrease of the systolic peak gradient from 78 +/- 24 to 38 +/- 13 mm Hg (p less than 0.001), and an increase in the aortic orifice area from 0.58 +/- 0.23 to 0.93 +/- 0.2 cm2 (p less than 0.001). The Doppler echocardiographic approach revealed that the maximal instantaneous gradient decreased from 96 +/- 26 to 67 +/- 22 mm Hg (p less than 0.001). The aortic orifice area increased from 0.49 +/- 0.16 to 0.73 +/- 0.21 cm2 (p less than 0.001). Three patients (8%) died in the hospital. After hospital discharge, 16 patients (44%) died and 8 patients (22%) underwent successful aortic valve replacement after a mean follow-up of 8 +/- 6 months. Nine patients (25%) were alive after a follow-up period of 18 months. Seven of these (19%) remained clinically improved. During follow-up, the Doppler echocardiographic results revealed a continuous trend toward the preprocedural severity of the aortic valve stenosis. Progression of restenosis assessed by Doppler echocardiographic measurements was accelerated in the group of patients who subsequently died or underwent repeat balloon valvuloplasty or aortic valve replacement. 相似文献