The purpose of this research is to characterize the effects of viral respiratory disease during early life on postnatal lung growth and development. Parainfluenza (Sendai) virus infection in rats is being used as an experimental model of viral bronchiolitis and pneumonia in human infants. Studies on viral respiratory disease in infants have shown that viral infection in the first 2 years of life is often associated with persistently abnormal subsequent lung function and a greater predisposition to chronic lung disease. The proposed research will determine the pathologic and morphometric changes that occur in lungs of young rats infected when the lung is rapidly growing. The research will also examine virologic and immunologic mechanisms that may play a role in making young animals more susceptible to viral lung damage during early life. Quantitative morphology studies will focus in detail on ultrastructural morphometric alterations in postnatal growth of alveolar parenchyma that may decrease the diffusion capacity of exchange tissue in viral-infected infants. Morphometric studies on airway corrosion casts of viral-infected infant rats will focus on viral-induced changes in airway growth that may contribute to obstruction of conducting airways. Viral-induced changes in lung compliance will be assessed by static saline pressure-volume physiologic studies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
7R01HL033441-03
Application #
3345362
Study Section
Pathology A Study Section (PTHA)
Project Start
1987-01-01
Project End
1987-12-31
Budget Start
1987-01-01
Budget End
1987-12-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Veterinary Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Uhl, E W; Moldawer, L L; Busse, W W et al. (1998) Increased tumor necrosis factor-alpha (TNF-alpha) gene expression in parainfluenza type 1 (Sendai) virus-induced bronchiolar fibrosis. Am J Pathol 152:513-22
Uhl, E W; Castleman, W L; Sorkness, R L et al. (1996) Parainfluenza virus-induced persistence of airway inflammation, fibrosis, and dysfunction associated with TGF-beta 1 expression in brown Norway rats. Am J Respir Crit Care Med 154:1834-42
Sorden, S D; Castleman, W L (1995) Virus-induced increases in airway mast cells in brown Norway rats are associated with enhanced pulmonary viral replication and persisting lymphocytic infiltration. Exp Lung Res 21:197-213
Sorden, S D; Castleman, W L (1995) Virus-induced increases in bronchiolar mast cells in Brown Norway rats are associated with both local mast cell proliferation and increases in blood mast cell precursors. Lab Invest 73:197-204
Cypcar, D; Lemanske Jr, R F (1994) Asthma and exercise. Clin Chest Med 15:351-68
Sorden, S D; Castleman, W L (1991) Brown Norway rats are high responders to bronchiolitis, pneumonia, and bronchiolar mastocytosis induced by parainfluenza virus. Exp Lung Res 17:1025-45
Sorden, S D; Lemanske Jr, R F; Castleman, W L (1990) Pulmonary eosinophilia and granulomatous pulmonary arteritis induced in rats by intravenous Sephadex. Vet Pathol 27:217-22
Castleman, W L; Sorkness, R L; Lemanske Jr, R F et al. (1990) Viral bronchiolitis during early life induces increased numbers of bronchiolar mast cells and airway hyperresponsiveness. Am J Pathol 137:821-31
Castleman, W L; Owens, S B; Brundage-Anguish, L J (1989) Acute and persistent alterations in pulmonary inflammatory cells and airway mast cells induced by Sendai virus infection in neonatal rats. Vet Pathol 26:18-25
Castleman, W L; Northrop, P J; McAllister, P K (1989) Replication of parainfluenza (Sendai) virus in isolated rat pulmonary type II alveolar epithelial cells. Am J Pathol 134:1135-42

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