Desmosomal component expression in normal, dysplastic, and oral squamous cell carcinoma.

Squamous cell carcinoma (oral SCC) is the most common oral cancer in the U.S., affecting nearly 30,000 Americans each year. Despite recent advances in detection and treatment, there has been little improvement in the five-year survival rate for this devastating disease. Oral cancer may be preceded by premalignant disease that appears histologically as dysplasia. Identification of molecular markers for cellular change would assist in determining the risk of dysplasia progressing to oral squamous cell carcinoma. The goal of this study was to determine if any correlation exists between histological diagnosed dysplasia and OSCC lesions and altered expression of desmosomal cell-cell adhesion molecules in the oral epithelium. Our data showed that oral SCC tissue samples showed decreased immunoreactivity of both desmoplakin and plakophilin-1 proteins compared to normal oral epithelium. Furthermore, significant decrease in desmoplakin immunoreactivity was observed in dysplastic tissue compared to normal oral epithelium. In contrast, the level of desmoglein-1 staining was unchanged between samples however desmoglein-1 was found localized to cell borders in oral SCC samples. These data suggest that changes in expression of desmoplakin and plakophilin-1 may prove to be a useful marker for changes in tissue morphology and provide a tool for identifying pre-neoplastic lesions of the oral cavity.

Molecular surface electrostatic potentials and anesthetic activity.

General anesthetics apparently act through weak, noncovalent and reversible interactions with certain sites in appropriate brain proteins. As a means of gaining insight into the factors underlying anesthetic potency, we have analyzed the computed electrostatic potentials V (S)(r) on the surfaces of 20 molecules with activities that vary between zero and high. Our results are fully consistent with, and help to interpret, what has been observed experimentally. We find that an intermediate level of internal charge separation is required; this is measured by Pi, the average absolute deviation of V (S)(r), and the approximate window is 7 < Pi < 13 kcal mol(-1). This fits in well with the fact that anesthetics need to be lipid soluble, but also to have some degree of hydrophilicity. We further show that polyhalogenated alkanes and ethers, which include the most powerful known anesthetics, have strong positive potentials, V (S,max), associated with their hydrogens, chlorines and bromines (but not fluorines). These positive sites may impede the functioning of key brain proteins, for example by disrupting their normal hydrogen-bond patterns. It has indeed been recognized for some time that the most active polyhalogenated alkanes and ethers contain hydrogens usually in combination with chlorines and/or bromines.