Recent studies have implicated the lipid mediator platelet-activating factor (PAF) in UVB-mediated systemic immunosuppression known to be a major cause for skin cancers. Previously, our group has demonstrated that UVB irradiation triggers the production of PAF and oxidized glycerophosphocholines that act as PAF-receptor (PAF-R) agonists. The present studies explored the mechanisms by which UVB generates PAF-R agonists. UVB irradiation of human epidermal KB cells resulted in both increased levels of reactive oxygen species (ROS) and PAF-R agonistic activity. Pretreatment of KB cells with antioxidants vitamin C and N-acetylcysteine or the pharmacological inhibitor PD168393 specific for the epidermal growth factor receptor all inhibited UVB-induced ROS as well as PAF-R agonists, yet had no effect on fMLP-mediated PAF-R agonist production. In addition, in vivo production of PAF-R agonists from UVB-irradiated mouse skin was blocked by both systemic vitamin C administration and topical PD168393 application. Moreover, both vitamin C and PD168393 abolished UVB-mediated but not the PAF-R agonist 1-hexadecyl-2-Nmethylcarbamoyl glycerophosphocholine-mediated immunosuppression as measured by the inhibition of delayed type contact hypersensitivity to the chemical dinitrofluorobenzene. These studies suggest that UVB-induced systemic immunosuppression is due to epidermal growth factor receptor-mediated ROS which results in PAF-R agonist formation.Ultraviolet B (290-320 nm) radiation found in sunlight has a spectrum of profound effects on human skin ranging from vitamin D metabolism to skin aging and carcinogenesis (1,2). UVB exposure is believed to be the major cause for nonmelanoma skin cancer, the most common NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript type of human cancer (3,4). In addition to its ability to damage DNA, UVB is well known to exert an immunosuppressive effect via inhibiting cell-mediated immune responses that are indispensable for antitumor immunity (5,6). As such, effort has been put forth to study the mechanisms underlying UVB-induced immunosuppression, and contact allergy to chemical haptens such as dinitrofluorobenzene (DNFB) 3 has been widely used as a model (7).Platelet-activating factor (1-alkyl-2-acetyl glycerophosphocholine, PAF) is a potent inflammatory lipid mediator, exerting its effects through a single specific G-protein-coupled receptor, the PAF receptor (8). PAF is synthesized enzymatically in response to diverse stimuli including cytokines, endotoxin, Ca 2+ ionophores, and PAF itself (8-10). In addition, PAF and sn-2 short-chained acyl glycerophosphocholines (GPCs) with PAF-receptor (PAF-R) agonistic activity can also be produced through free radical-mediated damage (11). In contrast, PAFacetylhydrolase (PAF-AH) inactivates PAF and oxidized GPCs by hydrolyzing the acetyl oxidatively modified sn-2 group of the glycerol backbone (12). Previous studies by our group (13-17) and others (18)(19)(20) have indicated that PAF plays pivotal roles in mediating not ...

Methotrexate is a useful and well-tolerated therapy with considerable steroid-sparing effect in patients with pemphigus vulgaris. It may be considered a first-line adjuvant therapy in the treatment of this difficult disease.

Analogies and metaphors are frequently employed in medicine to explain difficult medical concepts and procedures to patients. Learning is enhanced when visual analogies are used to present new concepts, and the use of effective analogies decreases both learner (patient) and teacher (physician) anxiety. 1,2 This is a desirable result of physician-patient discussions about anxiety-inducing interventions, such as surgery.Patient education prior to Mohs micrographic surgery (MMS) is paramount, including a comprehensive discussion of the procedure, the steps involved, and the time necessary to perform these steps. 3 Certain abstract aspects of the Mohs procedure can be difficult for patients to conceptualize; therefore, clear and adequate physician-patient communication is essential. Metaphorical and analogical approaches are frequently employed in the field of dermatology and can be effectively used by the surgeon. 4 Expressions used to describe the Mohs procedure include "digging up a tree along with its roots" and the "iceberg" illustration. These analogies aid in explaining the infiltrative tumor growth patterns under the biopsy site and the possibility that residual malignant tissue may remain after skin biopsy.The peanut butter cup encased in its wrapper serves as a visual representation of the unprocessed tissue obtained by the initial tumor excision by MMS (Figure). The sloped edges of the peanut butter cup are analogous to the beveled edges of a primary Mohs excision, because the incisions are made at a 45°angle

Ultraviolet B radiation (UVB) is a potent stimulator of epidermal cytokine production which has been implicated in photoaggravated dermatoses. In addition to cytokines such as tumor necrosis factor-a (TNF-a), UVB generates bioactive lipids including platelet-activating factor (PAF). Our previous studies have demonstrated that UVB-mediated production of keratinocyte TNF-a is in part due to PAF. The current studies use a human PAF-receptor (PAF-R) negative epithelial cell line transduced with PAF-Rs and PAF-R-deficient mice to demonstrate that activation of the epidermal PAF-R along with UVB irradiation results in a synergistic production of TNF-a. It should be noted that PAF-R effects are mimicked by the protein kinase C (PKC) agonist phorbol myristic acetate, and are inhibited by pharmacological antagonists of the PKC gamma isoenzyme. These studies suggest that concomitant PAF-R activation and UVB irradiation results in a synergistic production of the cytokine TNF-a which is mediated in part via PKC. These studies provide a novel potential mechanism for photosensitivity responses.