The Pathology core will provide coordination for all pathology activities within the SCOR including histologic, morphometric, immunologic and molecular analysis to tissue. The Core thus provides a single resource that can be used to answer recurrent questions that arise in the understanding of both experimental models and human investigation into asthma. The creation of a core facility, under the supervision of investigators experienced in conventional morphologic analysis, immunology and molecular biology (Drs. Homer, Kashgarian, and Howe), will reduce duplication of effort among the different projects and allow a degree of expertise that would be difficult to achieve in any single project. Along with the technical advantages of a single morphologic core, the use of a single principle pathologist (Dr. Homer) will also promote uniform analysis of results allowing more ready comparison among the projects. Furthermore, by providing uniform assess to specialized morphologic techniques, this facility will form a focal point for collaboration among members of the grant. Technical services provided include routine paraffin embedded histology, plastic embedded tissue, electron microscopy, immunohistochemical stains of frozen paraffin embedded tissue, and in situ analysis for mRNA for cytokines. The results will be analyzed by a pulmonary pathologist for nature and extent of inflammatory change, microanatomic location of the infiltrate, presence of airway remodeling, and presence of epithelial injury. Any changes identified will be quantitated by morphometry where appropriate. The core will also develop new methods of analysis of pulmonary tissue. A major limitation of much of current molecular analysis of tissue is the use of frozen tissue in which histologic resolution is sacrificed for preservation of molecule of interest. We propose to circumvent these problems by investigating (a) antigen retrieval technology such as citrate buffer heating for formalin fixed, paraffin embedded tissues for immunohistochemistry and (b) improved fixation techniques such as acetone-methyl benzoate (AMeX) method for immunohistochemistry and in situ hybridization. Finally, the core will function as a teaching resource to facilitate and stimulate interdisciplinary inquiry among those investigators involved in basic experimental studies using animal models and those investigators conducting clinical and applied studies.
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