The role of prolactin and testosterone in mediating seasonal differences in the self-grooming behavior of male meadow voles, Microtus pennsylvanicus.

Self-grooming in response to the odors of conspecifics is a form of olfactory communication among meadow voles. The amount of time meadow voles spend self-grooming when they encounter the odors of conspecifics varies seasonally, with males targeting the odors of reproductively active females only during the breeding season. Other odor related behaviors in male voles such as odor preferences for conspecifics and the attractiveness of their odors to conspecifics vary seasonally as well. For male meadow voles, these behaviors are mediated by seasonal variations in testosterone (T) and prolactin (PRL) titers. The objective of this study was to determine whether seasonal differences in the amount of time male meadow voles self-groom in response to odors of conspecifics are mediated by seasonal rhythms in their circulating T and PRL titers. We tested the hypothesis that high titers of both T and PRL are necessary for reproductively active (long-photoperiod; LP) males and sufficient for reproductively quiescent (short-photoperiod; SP) male voles to spend more time self-grooming in response to odors of LP females than to those of other conspecifics. Results of this study demonstrate that high titers of PRL and T are necessary for LP male meadow vole to self-groom more in response to odors of LP females as compared to those of other conspecifics, but were not sufficient to induce SP males to preferentially self-groom to odors of LP females. The endocrine control of self-grooming by LP males appears to depend upon high titers of both PRL and T, which matches the endocrine mediation of other odor related behaviors in male voles. In contrast, the endocrine tissues that underlie self-grooming in SP male meadow voles appear to be refractory to the effects of LP-equivalent titers of PRL and T.

A far-red fluorescent contrast agent to image epidermal growth factor receptor expression.

Recent developments in optical technologies have the potential to improve the speed and accuracy of screening and diagnosis of curable precancerous lesions and early cancer, thereby decreasing the costs of detection and management of epithelial malignancies. The development of molecular-specific contrast agents for markers of early neoplastic transformation could improve the detection and molecular characterization of premalignant lesions. In the oral cavity, epidermal growth factor receptor (EGFR) overexpression has been identified in early stages of premalignant lesions of the oral squamous cell carcinoma; therefore, real-time assessment of EGFR expression could serve as a biomarker for oral neoplasia. The purpose of our study was to develop a molecular-specific optical contrast agent targeted against EGFR for in vivo assessment of epithelial neoplasia using a monoclonal antibody and the far-red fluorescent dye, Alexa Fluor 660 streptavidin. In addition to demonstrating the specificity of the contrast agent for EGFR in cell lines, we document the ability to achieve penetration through 500 microm thick epithelial layers using multilayer tissue constructs and permeability-enhancing agents. Finally, using the fluorescence intensity of the contrast agent on fresh oral cavity tissue sections, we were able to distinguish abnormal from normal oral tissue. This contrast agent should have important clinical applications for use in conjunction with fluorescence spectroscopy or imaging (or both) to facilitate tumor detection and demarcation.

Vision enhancement system for detection of oral cavity neoplasia based on autofluorescence.

BACKGROUND: Early detection of squamous cell carcinoma (SCC) in the oral cavity can improve survival. It is often difficult to distinguish neoplastic and benign lesions with standard white light illumination. We evaluated whether a technique that capitalizes on an alternative source of contrast, tissue autofluorescence, improves visual examination. METHODS: Autofluorescence of freshly resected oral tissue was observed visually and photographed at specific excitation/emission wavelength combinations optimized for response of the human visual system and tissue fluorescence properties. Perceived tumor margins were indicated for each wavelength combination. Punch biopsies were obtained from several sites from each specimen. Sensitivity and specificity were evaluated by correlating histopathologic diagnosis with visual impression. RESULTS: Best results were achieved with illumination at 400 nm and observation at 530 nm. Here, sensitivity and specificity were 91% and 86% in discrimination of normal tissue from neoplasia. This compares favorably with white light examination, in which sensitivity and specificity were 75% and 43%. CONCLUSIONS: Oral cavity autofluorescence can be easily viewed by the human eye in real time. Visual examination of autofluorescence enhances perceived contrast between normal and neoplastic oral mucosa in fresh tissue resections.

Confocal microscopy for real-time detection of oral cavity neoplasia.

PURPOSE: The goal of this study was to characterize features of normal and neoplastic oral mucosa using reflectance confocal microscopy. EXPERIMENTAL DESIGN: Oral cavity biopsies were acquired from 17 patients at the Head and Neck Clinic of The University of Texas M. D. Anderson Cancer Center who were undergoing surgery for squamous cell carcinoma within the oral cavity. Reflectance confocal images were obtained at multiple image plane depths from biopsies within 6 h of excision. After imaging, biopsies were fixed in 10% formalin and submitted for routine histological examination. Reflectance confocal images were compared with histological images from the same sample to determine which tissue features contribute to image contrast and can be potentially imaged using in vivo confocal microscopy. RESULTS: Confocal images were successfully acquired from 15 biopsy pairs from 17 patients. Depth-related changes in cell diameter and nuclear density were observed at multiple anatomical sites within the oral cavity. In squamous cell carcinomas, densely packed, pleomorphic tumor nuclei could be visualized with distinct differences in nuclear density and morphology distinguishable between confocal images of neoplastic and nonneoplastic oral cavity. Other features of noncancerous and cancerous oral tissue that could be identified in the confocal images included areas of inflammation, fibrosis, muscle fibers, and salivary glands. CONCLUSIONS: Our results support the potential for this tool to play a significant role in the clinical evaluation of oral lesions, real-time identification of tumor margins, and monitoring of response to therapeutic treatment.