This project is concerned with 1) the systematic definition and characterization of the small-granule, presumptively endocrine cells of the mammalian lung; 2) the fetal development and maturation of these cells and their subsequent turnover in the adult; 3) the origin of endocrine-cell human lung tumors and improved methods for their diagnosis. Recently, we have developed two simple, reliable light microscopic methods for demonstrating small-granule cells in glycol methacrylate-embedded lungs of hamsters, rabbits, mice and cats and in a variety of human pulmonary tumors: 1) PAS-lead hematoxylin staining, and 2) a stable, aqueous formaldehyde-induced serotonin fluorescence. With these methods, we will continue systematic studies of the distribution of small-granule cells in hamster and mouse lungs using 3-dimensional airway reconstructions. Written descriptions for data analysis include the number and staining characteristics of endocrine cells; their position in the airway with respect to branch points, bronchiolar-alveolar portals; airway branching order and size; the nature of immediately adjacent epithelial cells; the presence or absence of underlying smooth muscle, nerves and vessels. Coordinated electron microscopy also will be carried out as will trial immunocytochemical localizations for hormones produced ectopically by lung tumors. Serotonin fluorescence, argyrophil and PAS-lead hematoxylin methods will be applied conjunctively to study fetal development and maturation of these cells in fetal hamster lung and will be coupled with autoradiographic studies of cell turnover in the adult. Conjunctive light microscopic staining and electron microscopy will be applied to human lung tumors to characterize their constituent cells and to investigate their relationship with normal elements of the bronchial epithelium.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL019379-09
Application #
3335820
Study Section
Pathology A Study Section (PTHA)
Project Start
1976-06-01
Project End
1987-03-31
Budget Start
1985-04-01
Budget End
1987-03-31
Support Year
9
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Boston University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
Ebina, M; Hoyt Jr, R F; McNelly, N A et al. (1997) Effects of hydrogen and bicarbonate ions on endocrine cells in fetal rat lung organ cultures. Am J Physiol 272:L178-86
Sorokin, S P; Hoyt Jr, R F; Shaffer, M J (1997) Ontogeny of neuroepithelial bodies: correlations with mitogenesis and innervation. Microsc Res Tech 37:43-61
McDowell, E M; Sorokin, S P; Hoyt Jr, R F (1994) Ontogeny of endocrine cells in the respiratory system of Syrian golden hamsters. I. Larynx and trachea. Cell Tissue Res 275:143-56
McDowell, E M; Hoyt Jr, R F; Sorokin, S P (1994) Ontogeny of endocrine cells in the respiratory system of Syrian golden hamsters. II. Intrapulmonary airways and alveoli. Cell Tissue Res 275:157-67
Hoyt Jr, R F; Sorokin, S P; McDowell, E M et al. (1993) Neuroepithelial bodies and growth of the airway epithelium in developing hamster lung. Anat Rec 236:15-22;discussion 22-4
Ebina, M; Hoyt Jr, R F; Sorokin, S P et al. (1993) Calcium and ionophore A23187 lower calcitonin gene-related peptide-like immunoreactivity in endocrine cells of organ cultured fetal rat lungs. Anat Rec 236:226-30
Hoyt Jr, R F; McNelly, N A; McDowell, E M et al. (1991) Neuroepithelial bodies stimulate proliferation of airway epithelium in fetal hamster lung. Am J Physiol 260:L234-40
Hoyt Jr, R F; McNelly, N A; Sorokin, S P (1990) Dynamics of neuroepithelial body (NEB) formation in developing hamster lung: light microscopic autoradiography after 3H-thymidine labeling in vivo. Anat Rec 227:340-50
Hoyt Jr, R F; Sorokin, S P; McDowell, E M et al. (1986) Periodic acid-Schiff-lead hematoxylin as a marker for the endocrine phenotype in human lung tumors. Arch Pathol Lab Med 110:943-51
Sarikas, S N; Hoyt Jr, R F; Sorokin, S P (1985) Ontogeny of small-granule APUD cells in hamster lung: a morphological study. Anat Rec 213:396-409

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