Ultraviolet radiation-induced cytokines promote mast cell accumulation and matrix metalloproteinase production: potential role in cutaneous lupus erythematosus.

OBJECTIVE: To examine the role of mast cells (MCs), cytokines, and matrix metalloproteinases (MMPs) following ultraviolet B (UVB) radiation in cutaneous lupus erythematosus (CLE). METHODS: Immunohistochemistry was used to determine the presence of MCs and the expression of MMP-1, MMP-9, interleukin (IL)-15, and CCL5/RANTES in skin from patients with CLE. Human keratinocytes were exposed to varying doses of UVB and supernatants were collected and assessed for IL-15, CCL5, MMP-1, and MMP-9 by protein assays. MC migration was determined against supernatants from UVB-treated keratinocytes. RESULTS: MCs in the skin of patients with CLE were significantly increased. MMP-1 and MMP-9 expression was abundant in these lesions. Intense reactivity for IL-15 and CCL5 was found in skin, particularly in epidermal keratinocytes, from patients with CLE. UVB irradiation induced IL-15, CCL5, MMP-1, and MMP-9 production from keratinocytes in a dose- and time-dependent manner. Supernatants obtained from UVB-treated keratinocytes induced MC migration, which was attenuated by anti-IL-15 and anti-CCL5 neutralizing antibodies. IL-15 induced MC-derived MMP production. CONCLUSIONS: Our results indicate that MCs and MMPs may play a role in the skin inflammation in CLE. MC recruitment as well as MMP production may be perpetuated by UV irradiation through locally released mediators.

Butterfly lesion of the corpus callosum due to Schilder's disease.

A 50 year old woman developed memory impairment and confusion over a 2 week period. CT scans of the brain showed a 'butterfly lesion' of the corpus callosum extending into the frontal lobes bilaterally. Stereotactic biopsy determined the lesion to be du e to demyelination. Further diagnostic investigations and the subsequent clinical course support the diagnosis of Schilder's disease.

Colorectal carcinomas arising in the hyperplastic polyposis syndrome progress through the chromosomal instability pathway.

The hyperplastic polyposis syndrome is characterized by the presence within the colon of multiple large hyperplastic polyps. We describe a case of hyperplastic polyposis syndrome associated with two synchronous carcinomas, one of which arises within a pre-existing hyperplastic lesion. Comparative genomic hybridization was used to determine genetic changes in both carcinomas and several associated hyperplastic lesions. Microsatellite analysis at five loci was performed on carcinomas and representative hyperplastic polyps, and p53 status was analyzed by immunohistochemistry. Both carcinomas showed multiple genetic aberrations, including high level gains of 8q and 13q, and loss of 5q. These changes were not seen in the hyperplastic polyps. Microsatellite instability was not seen in the carcinomas, four separate hyperplastic polyps, the hyperplastic polyp with mild adenomatous change associated with the carcinoma, or a separate serrated adenoma. Allelic imbalance in the cancers at D5S346 and D17S938 suggested allelic loss of both p53 and APC, as well as at the loci D13S263, D13S174, D13S159, and D18S49. An early invasive carcinoma in one hyperplastic polyp stained for p53 protein, but the associated hyperplastic polyp was negative. In this case, neoplastic progression followed the typical genetic pathway of common colorectal carcinoma and occurred synchronously with mutation of p53.

Helicobacter pylori infection in children: potential clues to pathogenesis.

Children (227) undergoing endoscopy for upper gastrointestinal symptoms were investigated for the presence of Helicobacter pylori infection. The histological response to H. pylori infection and the presence of antral nodularity and peptic ulceration were noted. Symptomatic adults (258) undergoing endoscopy were also investigated for the presence of nodularity. H. pylori infection was detected histologically in 32 of 227 (14.1%) children. Of those children infected with H. pylori, half (50%) had antral nodular gastritis. Of 139 H. pylori-positive adults 22 (15.8%) showed nodularity. The active component of the histological response was found to be minimal or lacking in the majority of children infected with H. pylori. Twelve of the 227 children (5.3%) had peptic ulcer disease. Of these, nine were duodenal and three gastric ulcers. Of the nine children with duodenal ulceration three (33%) were infected with H. pylori. As a result of this study we conclude that (a) although antral nodularity occurs more frequently in children it is not exclusive to childhood, (b) the polymorphonuclear response in children is less than that reported in adults, and (c) peptic ulcer disease is rare in children and the present study would suggest that in children it is less frequently associated with H. pylori infection than in adults.

Sporotrichosis: a review of 39 cases.

In a series of 39 cases of cutaneous sporotrichosis, 37 were of the localized cutaneous type and only 2 of the lymphangitic variety. Fungi were identified histologically in every case, most often as asteroid bodies which were found in all but 3 lesions. Cultures were occasionally negative even though asteroids or yeast-like forms were present in tissue sections. A histological diagnosis should be possible in all cases if a sufficient number of serial sections are examined by H & E and the PAS method.