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M9480420.TXT
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1994-08-20
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Document 0420
DOCN M9480420
TI Experimental large-animal model of obliterative bronchiolitis after lung
transplantation.
DT 9410
AU al-Dossari GA; Kshettry VR; Jessurun J; Bolman RM 3rd; Division of
Cardiovascular and Thoracic Surgery, University of; Minnesota,
Minneapolis 55455-0392.
SO Ann Thorac Surg. 1994 Jul;58(1):34-9; discussion 39-40. Unique
Identifier : AIDSLINE MED/94311708
AB Obliterative bronchiolitis is a major cause of long-term morbidity after
lung transplantation. It is characterized by small-airway inflammation
and occlusion by fibrous tissue. The pathogenesis is uncertain. To study
this disease, we developed a model of posttransplantation obliterative
bronchiolitis using genetically defined miniature swine. Group 1 (n = 2)
received a left lung autograft; group 2 (n = 7), a left lung allograft.
Group 2 recipients were given cyclosporine, prednisone, and azathioprine
for 3 months, then immunosuppression was tapered and discontinued over 1
month. The animals were observed for an additional 2 months, then
sacrificed. Lung grafts in both groups were monitored with serial
bronchoalveolar lavages and transbronchial biopsies for 6 months. After
sacrifice, lung grafts underwent histopathologic and immunohistochemical
examination. No allograft had histologic evidence of acute rejection or
peribronchiolar infiltrate during the first 3 months of
immunosuppression. During the tapering period, airway changes
characterized by severe peribronchiolar lymphocytic infiltrates were
seen. Bronchoalveolar lavages of allografts showed significantly
increased lymphocyte counts with CD8+ cells predominating. After the
discontinuation of immunosuppression, transbronchial biopsy and autopsy
specimens showed progressive fibrous inflammatory occlusion of
bronchioles. Immunohistochemical staining demonstrated increased
expression of MCH class II antigen on the bronchiolar epithelium and
increased dendritic cells and CD4+ lymphocytes. None of these changes
were seen in group 1. Our findings suggest obliterative bronchiolitis is
an immunologically mediated phenomenon related to chronic graft
rejection after lung transplantation. This model will allow systematic
study of the pathogenesis of obliterative bronchiolitis and possible
therapeutic intervention.
DE Animal Biopsy Bronchi/PATHOLOGY Bronchiolitis
Obliterans/*IMMUNOLOGY/PATHOLOGY Bronchoalveolar Lavage Fluid/CYTOLOGY
Chronic Disease CD4-CD8 Ratio Disease Models, Animal Graft
Rejection/*IMMUNOLOGY/PATHOLOGY Immunosuppressive Agents/THERAPEUTIC
USE Lung/*PATHOLOGY Lung Transplantation/IMMUNOLOGY/*PATHOLOGY Swine
Swine, Miniature Time Factors JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).