Electron Microscopy of Intranuclear Inclusions Found in Human and Rat Liver Parenchymal Cells

Intranuclear inclusions generally concluded to represent a heterogeneous class of bodies are readily distinguishable from nucleoli, fat droplets, crystals, or melanin also found within nuclei. The intranuclear inclusions associated with virus infection have been broadly classified into two types by Cowdry, type A and type B (1). Both A and B inclusions exhibit morphological variations and the few histochemical studies indicate that not all A nor all B inclusions are chemically alike (1-3). The type B inclusion associated with poliomyelitis, Borna disease, Rift Valley fever (1), and salivary gland virus disease (cytomegalia) (4), often appears in cells where no apparent associatlon with virus etiology could be established. This led Cowdry in 1934 (1) to state, "Consequently with these type B inclusions the existence of a virus should not be taken for granted. They may be simply the expression of nuclear modifications occurring not only in some virus diseases but also in many conditions for which viruses are probably not responsible." Typical intranuclear inclusions have been reported to occur spontaneously in liver and kidney cells of several wild mammals and birds (5), in liver cells of "normal stock" mice (6-8), and in tissue culture cells of foetal leptomeninges (3). Similar nuclear inclusions have been experimentally induced by injections of aluminum hydroxide, ferric hydroxide and carbon (9), by lead poisoning and irradiation (10), and treatment with thioacetamide (11, 12). In a cytochemical study of nuclear inclusions of human, rat, and mouse liver with the light microscope (13) the inclusions were found to be round and to vary in size. They were acidophilic, Feulgen negative, and contained variable levels of basophilic material identified as ribonucleic acid, protein, and occa-