Abstract
The proliferative activity and ultrastructural characteristics of proliferating biliary epithelial cells were analysed immunohistocytochemically in 39 biopsied liver specimens from patients with acute viral hepatitis, chronic hepatitis and liver cirrhosis using a monoclonal antibody against DNA polymerase alpha (DNA-PA). In acute viral hepatitis with perivenular confluent necrosis, proliferation of typical bile ducts was found frequently in portal areas. In chronic aggressive hepatitis and cirrhosis, ductular proliferation of both typical and atypical forms was found in enlarged portal and periportal areas and in confluent necrotic areas. The number of proliferating biliary epithelial cells that stained positive for DNA-PA was small. There were very few positively stained cells in atypical bile ducts in confluent necrotic areas of cirrhosis. Atypical bile ducts seen in chronic aggressive hepatitis, cirrhosis and acute hepatitis with confluent necrosis were positively stained for both cytokeratins 8 and 19. In cirrhosis, the number of stained biliary epithelial cells in typical bile ducts was larger than the number of such cells in atypical bile ducts (P < 0.01). By electron microscopy, the cells positively stained for DNA-PA were mostly so-called clear cells with irregular nuclei containing coarse nucleoplasm, and a few small cells with scanty cytoplasm and few organelles.
MeSH Terms
Adult
Aged
Antibodies, Monoclonal/analysis,immunology
Bile Ducts/chemistry,pathology,ultrastructure
Biopsy
Cell Division
Chronic Disease
Cytoplasm/ultrastructure
DNA Polymerase II/analysis,immunology
Epithelium/chemistry,pathology,ultrastructure
Female
Hepatitis/metabolism,pathology
Hepatitis, Viral, Human/metabolism,pathology
Humans
Immunohistochemistry
Keratins/analysis,immunology
Liver/chemistry,pathology,ultrastructure
Liver Cirrhosis/metabolism,pathology
Liver Diseases/metabolism,pathology
Male
Microscopy, Electron
Middle Aged
Organelles/ultrastructure
Chemicals
Antibodies, Monoclonal
Keratins
DNA Polymerase II
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Seki S
Third Department of Internal Medicine, Osaka City University Medical School, Japan.
Sakaguchi H
Kawakita N
Yanai A
Kuroki T
Kobayashi K
References (27)
27 references, click to expand
-
The nature and origin of proliferated bile ductules in alcoholic liver disease.
Am J Clin Pathol. 1983 Mar;79(3):326-33
PMID: 6829503
-
Isolation of a nonparenchymal liver cell fraction enriched in cells with biliary epithelial phenotypes.
Gastroenterology. 1989 Nov;97(5):1248-60
PMID: 2477298
-
Monoclonal anti cytokeratin antibodies reveal bile duct origin of cirrhotic ductular proliferations (dp).
Virchows Arch A Pathol Anat Histopathol. 1985;407(2):233-5
PMID: 2411048
-
Origin, pattern, and mechanism of bile duct proliferation following biliary obstruction in the rat.
Gastroenterology. 1990 Aug;99(2):466-77
PMID: 1694804
-
S-phase cells in diseased human liver determined by an in vitro BrdU-anti-BrdU method.
Hepatology. 1988 Nov-Dec;8(6):1535-9
PMID: 2847968
-
General pathology of the liver: light microscopic aspects serving diagnosis and interpretation.
Semin Liver Dis. 1986 Aug;6(3):175-84
PMID: 3775396
-
Intracellular localization of human DNA polymerase alpha with monoclonal antibodies.
J Biol Chem. 1982 Jul 25;257(14):8391-6
PMID: 7045121
-
Keratin immunohistochemistry in normal human liver. Cytokeratin pattern of hepatocytes, bile ducts and acinar gradient.
Virchows Arch A Pathol Anat Histopathol. 1987;412(1):63-72
PMID: 2446418
-
Analysis of proliferating hepatocytes using a monoclonal antibody against proliferating cell nuclear antigen/cyclin in embedded tissues from various liver diseases fixed in formaldehyde.
Am J Pathol. 1992 Feb;140(2):513-20
PMID: 1346735
-
Intracellular localization and metabolism of DNA polymerase alpha in human cells visualized with monoclonal antibody.
Exp Cell Res. 1984 Mar;151(1):123-33
PMID: 6421608
-
Analysis of proliferative grade using anti-PCNA/cyclin monoclonal antibodies in fixed, embedded tissues. Comparison with flow cytometric analysis.
Am J Pathol. 1989 Apr;134(4):733-9
PMID: 2565087
-
Detection of proliferative cells in dysplasia, carcinoma in situ, and invasive carcinoma of the uterine cervix by monoclonal antibody against DNA polymerase alpha.
Cancer. 1988 Mar 15;61(6):1182-6
PMID: 3342375
-
Reciprocal modulation of growth and differentiated functions of mature rat hepatocytes in primary culture by cell--cell contact and cell membranes.
Proc Natl Acad Sci U S A. 1983 Dec;80(23):7229-33
PMID: 6580642
-
Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: A new reagent for detection of DNA replication.
Science. 1982 Oct 29;218(4571):474-5
PMID: 7123245
-
PROLIFERATION OF BILE DUCTS IN CIRRHOSIS.
Arch Pathol. 1964 Oct;78:421-31
PMID: 14184672
-
Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67.
J Immunol. 1984 Oct;133(4):1710-5
PMID: 6206131
-
Identification and fine structure of proliferating hepatocytes in malignant and nonmalignant liver diseases by use of a monoclonal antibody against DNA polymerase alpha.
Hum Pathol. 1990 Oct;21(10):1020-30
PMID: 2210724
-
ORIGIN AND FATE OF PROLIFERATED HEPATIC DUCTAL CELLS IN THE RAT: ELECTRON MICROSCOPIC AND AUTORADIOGRAPHIC STUDIES.
Exp Mol Pathol. 1964 Jun;3:242-61
PMID: 14194323
-
Electron microscopic studies of normal and proliferated bile ductules.
Am J Pathol. 1961 Apr;38:393-410
PMID: 13747220
-
Double immunoenzymatic detection of surface phenotype of proliferating lymphocytes in situ with monoclonal antibodies against DNA polymerase alpha and lymphocyte membrane antigens.
Am J Clin Pathol. 1987 Jun;87(6):725-31
PMID: 2438927
-
Production and characterization of monoclonal antibody against 10S DNA polymerase alpha from calf thymus.
Nucleic Acids Res. 1982 Aug 11;10(15):4703-13
PMID: 7133996
-
Detection of proliferating liver cells in various diseases by a monoclonal antibody against DNA polymerase-alpha: with special reference to the relationship between hepatocytes and sinusoidal cells.
Hepatology. 1991 Nov;14(5):781-8
PMID: 1718833
-
A cytokeratin immunohistochemical study of cholestatic liver disease: evidence that hepatocytes can express 'bile duct-type' cytokeratins.
Histopathology. 1989 Aug;15(2):125-35
PMID: 2476370
-
Bile ductules in cholestasis: morphologic evidence for secretion and absorption in man.
Lab Invest. 1967 Jan;16(1):84-95
PMID: 4164461
-
Ductular proliferation.
Gastroenterology. 1965 Dec;49(6):702-6
PMID: 5321231
-
Cell cycle dependent distribution of the proliferation-associated Ki-67 antigen in human embryonic lung cells.
Virchows Arch B Cell Pathol Incl Mol Pathol. 1988;56(1):25-33
PMID: 2907198
-
Electron microscopy of hyperplastic ductular cells in alpha-naphthyl isothiocyanateinduced cirrhosis.
Lab Invest. 1963 Apr;12:471-98
PMID: 13983744