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Ohne Zusammenfassung 相似文献
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Yawalkar N Shrikhande M Hari Y Nievergelt H Braathen LR Pichler WJ 《The Journal of allergy and clinical immunology》2000,106(6):1171-1176
BACKGROUND: Cutaneous drug reactions may be associated with increased numbers of eosinophils in the blood and tissue. However, the factors leading to the generation of eosinophilia have not been fully delineated. OBJECTIVE: The aim of this study was to investigate the in situ expression of IL-5, eotaxin, RANTES, monocyte chemoattractant protein 3, and IL-8 together with the appearance of eosinophils in acute cutaneous drug reactions. METHODS: Skin biopsy specimens were obtained from drug-induced maculopapular exanthems (n = 9), from normal skin of control subjects (n = 9), and from the skin of patients with psoriasis (n = 8). The in situ expression of IL-5, eotaxin, RANTES, monocyte chemoattractant protein 3, and IL-8 was analyzed by using immunohistochemistry. Furthermore, the corresponding numbers of eosinophils were determined in the blood and skin sections. RESULTS: Compared with normal skin and psoriatic skin, a significantly higher number of eosinophils was found both in the blood and tissue of patients with a drug-induced exanthem. In comparison with normal skin, immunoreactivity for IL-5 and all the chemokines was also significantly enhanced in drug-induced exanthem, whereas significant differences in psoriatic were only observed for IL-5 and eotaxin. CONCLUSION: Our data indicate that IL-5 and eotaxin may particularly contribute to the activation and recruitment of eosinophils and thereby play an important pathogenic part in the development of skin inflammation in drug-induced maculopapular exanthems. 相似文献
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Mechanical stretch induces podocyte hypertrophy in vitro 总被引:6,自引:0,他引:6
Petermann AT Pippin J Durvasula R Pichler R Hiromura K Monkawa T Couser WG Shankland SJ 《Kidney international》2005,67(1):157-166
BACKGROUND: Increased intraglomerular pressure is a final pathway toward glomerulosclerosis in systemic hypertension, diabetes, and focal segmental glomerulosclerosis (FSGS). Increased intraglomerular pressure causes stress-tension, or stretch, on resident glomerular cells. However, the effects of stretch on podocyte growth, and the mechanisms that underlie this, have not been elucidated. METHODS: To test the hypothesis that stretch alters podocyte growth, cultured mouse podocytes were exposed to cyclic mechanical stretch created by vacuum; control cells were grown under similar conditions, but not exposed to stretch. Proliferation (cell cycle phases) and hypertrophy (forward light scatter) were measured in stretched and control podocytes by flow cytometry. The role of the cyclin-dependent kinase (CDK) inhibitors, p21 and p27, was examined by stretching podocytes isolated from p21 and p27 knockout (-/-) mice, and the role of specific signaling pathways was assessed by Western blot analysis and blocking studies. RESULTS: Our results showed that stretch reduced cell cycle progression in wild-type and single p27-/- podocytes and induced hypertrophy in these cells in all phases of the cell cycle at 24, 48, and 72 hours. In contrast, stretch did not induce hypertrophy in single p21-/- and double p21/p27-/- podocytes. Stretch-induced hypertrophy required cell cycle entry, and was prevented by specifically blocking extracellular signal-regulated kinase 1/2 (Erk1/2) or Akt. Although stretch increased p38 activation, inhibition of this pathway had no effect on hypertrophy. CONCLUSION: Mechanical stretch induces hypertrophy in podocytes in vitro in all phases of the cell cycle. This effect is cell cycle dependent, and requires p21, Erk1/2, and Akt. Stretch may play a role in podocyte injury when intraglomerular pressure is increased. 相似文献