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ABSTRACT: Sweet's syndrome (SS) is an uncommon condition characterized by recurrent painful cutaneous inflammatory eruptions. It is rare in childhood and has a broad range of extracutaneous manifestations. We describe a child presenting with SS and postinflammatory elastolysis who subsequently developed aortitis complicated by aortic dilatation requiring surgical intervention. Histologic features of the aorta were consistent with Takayasu arteritis (TA). Our case and previously reported cases of pediatric SS complicated by aortitis all demonstrate striking clinical similarities in that all have been associated with postinflammatory elastolysis of involved skin and aneurysmal dilation of the thoracic aorta. We propose that TA should be considered one of the disease associations of SS when complicated by postinflammatory elastolysis and that early referral for cardiovascular screening be considered in this group of patients.
Pediatric Dermatology 10/2011; 29(5):645-50. · 1.07 Impact Factor
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Paul Bolitho,
Shayna E A Street,
Jennifer A Westwood,
Winfried Edelmann, Duncan Macgregor,
Paul Waring,
William K Murray,
Dale I Godfrey,
Joseph A Trapani,
Ricky W Johnstone,
Mark J Smyth
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ABSTRACT: In the present study, we have examined the effect of perforin (pfp) deficiency in 4 models of mouse B-cell lymphomagenesis. We have examined pfp loss on the background of either Mlh1 tumor suppressor allele loss or oncogene expression [Ig heavy chain (Emu)-v-Abl, Emu-myc, and vav-bcl2]. Pfp was shown to act as a suppressor of B-cell malignancies characteristically driven by v-Abl or bcl-2, whereas Mlh loss cooperated in accelerating spontaneous B-cell lymphomas characteristic of pfp loss. No protective role for pfp was observed in the more aggressive Emu-myc model of B-cell lymphoma. These transgenic models have allowed us to distinguish the role of pfp in surveillance of B-cell lymphomagenesis, as opposed to its loss simply driving the onset of a spontaneous lymphoma characteristic of pfp deficiency.
Proceedings of the National Academy of Sciences 03/2009; 106(8):2723-8. · 9.68 Impact Factor
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ABSTRACT: Most individuals with thin basement membrane nephropathy (TBMN) have an excellent prognosis. For these patients, the only hazards are the anxiety related to misconceptions about the diagnosis and the inconvenience, expense, and wastefulness of unnecessary investigations. However, there also are specific genetic implications for individuals with TBMN because, on average, half their offspring inherit the causative mutations and most of these have hematuria. In addition, despite the generally excellent outcome, some individuals with TBMN develop hypertension, proteinuria, or renal impairment. In some cases, renal failure is caused by apparently progressive but otherwise uncomplicated TBMN, and in others it results from a secondary or coincidental glomerular or tubulointerstitial renal lesion. In particular, TBMN appears to predispose to immunoglobulin (Ig)A glomerulonephritis, and the outcome for these patients is worse than for those with TBMN alone. The risks for patients with TBMN in relation to pregnancy and transplantation have not been well-studied but are described elsewhere in this issue.
Seminars in Nephrology 06/2005; 25(3):171-5. · 2.12 Impact Factor
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ABSTRACT: Few studies have demonstrated that innate lymphocytes play a major role in preventing spontaneous tumor formation. We evaluated the development of spontaneous tumors in mice lacking beta-2 microglobulin (beta2m; and thus MHC class I, CD1d, and CD16) and/or perforin, since these tumor cells would be expected to activate innate effector cells. Approximately half the cohort of perforin gene-targeted mice succumbed to spontaneous disseminated B cell lymphomas and in mice that also lacked beta2m, the lymphomas developed earlier (by more than 100 d) and with greater incidence (84%). B cell lymphomas from perforin/beta2m gene-targeted mice effectively primed cell-mediated cytotoxicity and perforin, but not IFN-gamma, IL-12, or IL-18, was absolutely essential for tumor rejection. Activated NK1.1+ and gammadeltaTCR+ T cells were abundant at the tumor site, and transplanted tumors were strongly rejected by either, or both, of these cell types. Blockade of a number of different known costimulatory pathways failed to prevent tumor rejection. These results reflect a critical role for NK cells and gammadeltaTCR+ T cells in innate immune surveillance of B cell lymphomas, mediated by as yet undetermined pathway(s) of tumor recognition.
Journal of Experimental Medicine 04/2004; 199(6):879-84. · 13.85 Impact Factor
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ABSTRACT: The immunosurveillance of transformed cells by the immune system remains one of the most controversial and poorly understood areas of immunity. Gene-targeted mice have greatly aided our understanding of the key effector molecules in tumor immunity. Herein, we describe spontaneous tumor development in gene-targeted mice lacking interferon (IFN)-gamma and/or perforin (pfp), or the immunoregulatory cytokines, interleukin (IL)-12, IL-18, and tumor necrosis factor (TNF). Both IFN-gamma and pfp were critical for suppression of lymphomagenesis, however the level of protection afforded by IFN-gamma was strain specific. Lymphomas arising in IFN-gamma-deficient mice were very nonimmunogenic compared with those derived from pfp-deficient mice, suggesting a comparatively weaker immunoselection pressure by IFN-gamma. Single loss of IL-12, IL-18, or TNF was not sufficient for spontaneous tumor development. A significant incidence of late onset adenocarcinoma observed in both IFN-gamma- and pfp-deficient mice indicated that some epithelial tissues were also subject to immunosurveillance.
Journal of Experimental Medicine 08/2002; 196(1):129-34. · 13.85 Impact Factor
