Eosinophilic variant of eccrine porocarcinoma of the scalp: Case report and review of the literature.

Porocarcinoma is a rare malignant neoplasm of the acrosyringium with metastatic potential that most commonly presents on the acral skin in older adults (mean age = 72 years). We present the case of a 43-year-old woman who developed a rapidly growing de novo porocarcinoma on the scalp with an unusual oncocytic appearance. The tumor consisted of benign eccrine poroma that arose from the epidermis and broad pushing borders with minimal cytological atypia but ample eosinophilic cytoplasm with numerous mitotic figures. Although some tumors may appear deceptively bland, the histologic recognition of pushing/infiltrative borders and mitotic figures are helpful to make the appropriate diagnosis of carcinoma. This lesion was treated with Mohs micrographic surgery and the patient remained free of recurrence after more than 2 years. It is important to recognize the eosinophilic variants of eccrine porocarcinoma because it can histologically mimic a squamous cell carcinoma.

Electrobrasion vs. manual dermabrasion: a randomized, double-blind, comparative effectiveness trial.

BACKGROUND: Electrobrasion, like dermabrasion, is a method of surgical planing that is purported to improve postoperative scarring. Data regarding its benefits and harms relative to dermabrasion are absent. OBJECTIVE: To compare the efficacy and potential harms of electrobrasion and dermabrasion. METHODS: This was a pragmatic, randomized, double-blind, split-scar intervention in patients with suboptimal surgical outcomes. Half of the wound was randomized to treatment with dermabrasion and half to electrobrasion. At 3-month follow-up, both the patient and a blinded investigator evaluated the wound. RESULTS: Electrobrasion and dermabrasion reduced the mean scores of the Manchester Scar Scale 1·6 and 1·3 points from baseline, respectively (P = 0·0003). The difference between treatments was not significant (P = 0·08). Global cosmetic improvement by physician and patient assessment indicated clinical improvement for both procedures but did not demonstrate statistical significance between treatments (P = 0·57, P = 0·32 for physician and patient, respectively). CONCLUSIONS: Both dermabrasion and electrobrasion improved scars, but there was no significant difference between the outcomes of the two procedures on several measures. Procedure time and bleeding time were significantly lower for electrobrasion.

Structural basis for fibroblast growth factor receptor 2 activation in Apert syndrome.

Apert syndrome (AS) is characterized by craniosynostosis (premature fusion of cranial sutures) and severe syndactyly of the hands and feet. Two activating mutations, Ser-252 --> Trp and Pro-253 --> Arg, in fibroblast growth factor receptor 2 (FGFR2) account for nearly all known cases of AS. To elucidate the mechanism by which these substitutions cause AS, we determined the crystal structures of these two FGFR2 mutants in complex with fibroblast growth factor 2 (FGF2). These structures demonstrate that both mutations introduce additional interactions between FGFR2 and FGF2, thereby augmenting FGFR2-FGF2 affinity. Moreover, based on these structures and sequence alignment of the FGF family, we propose that the Pro-253 --> Arg mutation will indiscriminately increase the affinity of FGFR2 toward any FGF. In contrast, the Ser-252 --> Trp mutation will selectively enhance the affinity of FGFR2 toward a limited subset of FGFs. These predictions are consistent with previous biochemical data describing the effects of AS mutations on FGF binding. Alterations in FGFR2 ligand affinity and specificity may allow inappropriate autocrine or paracrine activation of FGFR2. Furthermore, the distinct gain-of-function interactions observed in each crystal structure provide a model to explain the phenotypic variability among AS patients.

Crystal structure of fibroblast growth factor 9 reveals regions implicated in dimerization and autoinhibition.

Fibroblast growth factors (FGFs) constitute a large family of heparin-binding growth factors with diverse biological activities. FGF9 was originally described as glia-activating factor and is expressed in the nervous system as a potent mitogen for glia cells. Unlike most FGFs, FGF9 forms dimers in solution with a K(d) of 680 nm. To elucidate the molecular mechanism of FGF9 dimerization, the crystal structure of FGF9 was determined at 2.2 A resolution. FGF9 adopts a beta-trefoil fold similar to other FGFs. However, unlike other FGFs, the N- and C-terminal regions outside the beta-trefoil core in FGF9 are ordered and involved in the formation of a 2-fold crystallographic dimer. A significant surface area (>2000 A(2)) is buried in the dimer interface that occludes a major receptor binding site of FGF9. Thus, we propose an autoinhibitory mechanism for FGF9 that is dependent on sequences outside of the beta-trefoil core. Moreover, a model is presented providing a molecular basis for the preferential affinity of FGF9 toward FGFR3.

Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization.

The crystal structure of a dimeric 2:2:2 FGF:FGFR:heparin ternary complex at 3 A resolution has been determined. Within each 1:1 FGF:FGFR complex, heparin makes numerous contacts with both FGF and FGFR, thereby augmenting FGF-FGFR binding. Heparin also interacts with FGFR in the adjoining 1:1 FGF:FGFR complex to promote FGFR dimerization. The 6-O-sulfate group of heparin plays a pivotal role in mediating both interactions. The unexpected stoichiometry of heparin binding in the structure led us to propose a revised model for FGFR dimerization. Biochemical data in support of this model are also presented. This model provides a structural basis for FGFR activation by small molecule heparin analogs and may facilitate the design of heparin mimetics capable of modulating FGF signaling.

Synthesis and characterization of a novel class of protein tyrosine phosphatase inhibitors.

Nonpeptidyl aryloxymethylphosphonates were prepared and evaluated as protein tyrosine phosphatase inhibitors. The results suggest that aryloxymethylphosphonates are effective nonhydrolyzable phosphotyrosine surrogates and provide further insight into the molecular mechanisms by which phosphate mimics inhibit phosphatase function.

Antimicrobial properties of Honduran medicinal plants.

Ninety-two plants used in the traditional pharmacopoeia of the Pech and neighboring Mestizo peoples of central Honduras are reported. The results of in vitro antimicrobial screens showed that 19 of the extracts from medicinal plants revealed signs of antifungal activity while 22 demonstrated a measurable inhibitory effect on one or more bacterial cultures. Bioassay-guided fractionation of extracts from Mikania micrantha, Neurolaena lobata and Piper aduncum produced weak to moderately active isolates. The broad spectrum of activity of the extracts helps to explain the widespread use of these plants for wound healing and other applications.