Background and aims: Ulcerative colitis (UC) is characterised by refractory in flammatory ulceration and damage to the colon.The mechanisms underlying impaired healing have yet to be defined. As transglutaminase expre...Background and aims: Ulcerative colitis (UC) is characterised by refractory in flammatory ulceration and damage to the colon.The mechanisms underlying impaired healing have yet to be defined. As transglutaminase expression resulting in mat rix protein cross linking is associated with increased wound healing in a rat mo del of colitis, we hypothesised that different types of transglutaminase might a lso play a role in UC. Patients end methods: Endoscopic and histological indices were studied in 26 patients with UC (10 active and 16 inactive) and in 20 norma l controls undergoing colonoscopy. Transglutaminase activity was evaluated in pl asma (factor XIIIa) by a radioenzymatic metho- d. Factor XIIIa, tissue and keratinocyte transglutaminase protein content, and mRNA expression in the colon were evaluated by western blot analysis and semiqu antitative reverse transcription-polymerase chain reaction (RT-PCR),respectively. Colon ic location of transglutaminases and their reaction products, the -(γ-glutamy l)lysine bonds, was evaluated by immunohistochemistry using specific monoclonal antibodies.Results: Transglutaminase activity was significantly lower in the pla sma of patients with active UC (4.2 (2.4) mU/ml;p< 0.05 v controls) than in thos e with inactive UC and controls(10.6 (2.2) and 12.1 (1.7) mU/ml). As shown by we stern blot,protein levels of tissue transglutaminase and factor XIIIa were uncha nged in active UC compared with inactive disease and controls, while the keratin ocyte form was reduced in active UC. Tissue transglutaminase and factor XIIIa im munostaining was strongly present in damaged areas colocalising with isopeptide bonds. In contrast, the keratinocyte form was almost absent in active UC and loc alised in the upper part of the crypts in normal subjects. RT-PCR showed upregu lation of tissue transglutaminase mRNA in active UC (320%compared with controls ) while keratinocyte transglutaminase gene expression was downregulated in activ e UC. Conclusions: The results of the present study support the展开更多
Introduction. We report on a patient who progressively developed polymorphic expressions of neutrophilic dermatosis (Sneddon- Wilkinson subcorneal pustulosis and pyoderma gangrenosum) associated with p-antineutrophil ...Introduction. We report on a patient who progressively developed polymorphic expressions of neutrophilic dermatosis (Sneddon- Wilkinson subcorneal pustulosis and pyoderma gangrenosum) associated with p-antineutrophil cytoplasmic antibodies (p-ANCA), while receiving propylthiouracil for hyperthyroidism. To our knowledge, such associations have never been published so far. Case- report. A 40 year-old woman was treated with propylthiouracil for Graves’disease. After 16 months of therapy, she noted flares of pustular lesions surrounded with erythematous halo mainly localized on the trunk. The lesions became chronic, and were not improved by potent topical corticosteroids. When first seen in our department in February 2003, the eruption was typical of Sneddon-Wilkinson subcorneal pustulosis. This diagnosis was confirmed by the histological examination of a skin biopsy of a pustule. One month later, she developed an inflammatory progressively ulcerative lesion on the right ankle, typical of pyoderma gangrenosum. The diagnosis was confirmed by the histological examination of a skin biopsy taken on the evolving border of the lesion and showed polynuclear neutrophilic infiltration without vasculitis. Direct immunofluorescence was negative. The presence of serum anti-myeloperoxydase p-ANCA was known for this patient since October 2002. No IgA monoclonal gammapathy was revealed on extensive biological check-up. Systemic oral corticosteroid therapy (1 mg/kg/day) dramatically improved skin lesions with complete healing within 8 weeks. Discussion. Propylthiouracil is well known to induce the occurrence of ANCA in 20 to 64p. 100 of patients treated for Graves’disease. The mechanisms involved are badly recognized so far. Cutaneous vasculitis, glomerulonephritis and polychondritis may be clinically associated with those antibodies. Rare observations of neutrophilic dermatosis, mostly Sweet’ s syndrome, have been described in patients with propylthiouracil- induced ANCA. One case-report described a 44 year-old woman who deve展开更多
文摘Background and aims: Ulcerative colitis (UC) is characterised by refractory in flammatory ulceration and damage to the colon.The mechanisms underlying impaired healing have yet to be defined. As transglutaminase expression resulting in mat rix protein cross linking is associated with increased wound healing in a rat mo del of colitis, we hypothesised that different types of transglutaminase might a lso play a role in UC. Patients end methods: Endoscopic and histological indices were studied in 26 patients with UC (10 active and 16 inactive) and in 20 norma l controls undergoing colonoscopy. Transglutaminase activity was evaluated in pl asma (factor XIIIa) by a radioenzymatic metho- d. Factor XIIIa, tissue and keratinocyte transglutaminase protein content, and mRNA expression in the colon were evaluated by western blot analysis and semiqu antitative reverse transcription-polymerase chain reaction (RT-PCR),respectively. Colon ic location of transglutaminases and their reaction products, the -(γ-glutamy l)lysine bonds, was evaluated by immunohistochemistry using specific monoclonal antibodies.Results: Transglutaminase activity was significantly lower in the pla sma of patients with active UC (4.2 (2.4) mU/ml;p< 0.05 v controls) than in thos e with inactive UC and controls(10.6 (2.2) and 12.1 (1.7) mU/ml). As shown by we stern blot,protein levels of tissue transglutaminase and factor XIIIa were uncha nged in active UC compared with inactive disease and controls, while the keratin ocyte form was reduced in active UC. Tissue transglutaminase and factor XIIIa im munostaining was strongly present in damaged areas colocalising with isopeptide bonds. In contrast, the keratinocyte form was almost absent in active UC and loc alised in the upper part of the crypts in normal subjects. RT-PCR showed upregu lation of tissue transglutaminase mRNA in active UC (320%compared with controls ) while keratinocyte transglutaminase gene expression was downregulated in activ e UC. Conclusions: The results of the present study support the
文摘Introduction. We report on a patient who progressively developed polymorphic expressions of neutrophilic dermatosis (Sneddon- Wilkinson subcorneal pustulosis and pyoderma gangrenosum) associated with p-antineutrophil cytoplasmic antibodies (p-ANCA), while receiving propylthiouracil for hyperthyroidism. To our knowledge, such associations have never been published so far. Case- report. A 40 year-old woman was treated with propylthiouracil for Graves’disease. After 16 months of therapy, she noted flares of pustular lesions surrounded with erythematous halo mainly localized on the trunk. The lesions became chronic, and were not improved by potent topical corticosteroids. When first seen in our department in February 2003, the eruption was typical of Sneddon-Wilkinson subcorneal pustulosis. This diagnosis was confirmed by the histological examination of a skin biopsy of a pustule. One month later, she developed an inflammatory progressively ulcerative lesion on the right ankle, typical of pyoderma gangrenosum. The diagnosis was confirmed by the histological examination of a skin biopsy taken on the evolving border of the lesion and showed polynuclear neutrophilic infiltration without vasculitis. Direct immunofluorescence was negative. The presence of serum anti-myeloperoxydase p-ANCA was known for this patient since October 2002. No IgA monoclonal gammapathy was revealed on extensive biological check-up. Systemic oral corticosteroid therapy (1 mg/kg/day) dramatically improved skin lesions with complete healing within 8 weeks. Discussion. Propylthiouracil is well known to induce the occurrence of ANCA in 20 to 64p. 100 of patients treated for Graves’disease. The mechanisms involved are badly recognized so far. Cutaneous vasculitis, glomerulonephritis and polychondritis may be clinically associated with those antibodies. Rare observations of neutrophilic dermatosis, mostly Sweet’ s syndrome, have been described in patients with propylthiouracil- induced ANCA. One case-report described a 44 year-old woman who deve
