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Toxicity of lead-contaminated sediment to mallards.

Because consumption of lead-contaminated sediment has been suspected as the cause of waterfowl mortality in the Coeur d'Alene River basin in Idaho, we studied the bioavailability and toxicity of this sediment to mallards (Anas platyrhynchos). In experiment 1, one of 10 adult male mallards died when fed a pelleted commercial duck diet that contained 24% lead-contaminated sediment (with 3,400 microgram/g lead in the sediment). Protoporphyrin levels in the blood increased as the percentage of lead-contaminated sediment in the diet increased. Birds fed 24% lead-contaminated sediment exhibited atrophy of the breast muscles, green staining of the feathers around the vent, viscous bile, green staining of the gizzard lining, and renal tubular intranuclear inclusion bodies. Mallards fed 24% lead-contaminated sediment had means of 6.1 microgram/g of lead in the blood and 28 microgram/g in the liver (wet-weight basis) and 1,660 microgram/g in the feces (dry-weight basis). In experiment 2, we raised the dietary concentration of the lead-contaminated sediment to 48%, but only about 20% sediment was actually ingested due to food washing by the birds. Protoporphyrin levels were elevated in the lead-exposed birds, and all of the mallards fed 48% lead-contaminated sediment had renal tubular intranuclear inclusion bodies. The concentrations of lead in the liver were 9.1 microgram/g for mallards fed 24% lead-contaminated sediment and 16 microgram/g for mallards fed 48% lead-contaminated sediment. In experiment 3, four of five mallards died when fed a ground corn diet containing 24% lead-contaminated sediment (with 4,000 microgram/g lead in this sample of sediment), but none died when the 24% lead-contaminated sediment was mixed into a nutritionally balanced commercial duck diet; estimated actual ingestion rates for sediment were 14% and 17% for the corn and commercial diets. Lead exposure caused elevations in protoporphyrin, and four of the five mallards fed 24% lead-contaminated sediment in a commercial diet and all five fed the contaminated sediment in a corn diet had renal intranuclear inclusion bodies. Lead was higher in the livers of mallards fed 24% lead-contaminated sediment in the corn diet (38 microgram/g) than in the commercial diet (13 microgram/g).

Administration, Oral↗

Probable herpesvirus infection in an eastern cottontail (Sylvilagus floridanus).

One wild eastern cottontail (Sylvilagus floridanus) from Milwaukee County, Wisconsin was necropsied. The lungs contained numerous multifocal, circumscribed, tan foci; the spleen was markedly enlarged and had a mottled reddish tan color; and the brain had a red to tan friable tract in the left hemisphere. Microscopically, the lung had a severe bronchiolitis and pneumonia. The bronchiolitis was characterized by epithelial cells containing eosinophilic intranuclear inclusion bodies. The encephalomalacia of the left cerebral cortex featured tissue disruption and astrocytes or neurons containing intranuclear inclusion bodies. Herpesvirus particles were found within the bronchiolar epithelial cells. Based on histopathological and ultrastructural findings, a herpesvirus seemed the most likely etiologic agent.

Animals↗

Cellular stress response induces selective intranuclear trafficking and accumulation of morbillivirus major core protein.

BACKGROUND: Using canine distemper virus (CDV) encephalomyelitis as a model for morbillivirus-induced intranuclear inclusion body (INB) formation, we previously demonstrated that the cellular basis for INB within infected astrocytes are viral antigen-associated nucleolar derivatives known as complex nuclear bodies. Here, we examined the relationship between the cellular stress response and intranuclear CDV protein trafficking so that we may begin to define cellular events leading to formation of complex nuclear bodies containing viral protein. EXPERIMENTAL DESIGN: Confocal dual-label immunofluorescence microscopy was used to simultaneously determine the distribution of CDV antigen and the major inducible 70 kilodalton (kd) heat shock protein (i.e., 72 kd heat shock protein (HSP)) within infected canine central nervous tissue. This dual-label immunofluorescent technique was also used to test the relationship between cellular stress and CDV core protein distribution in a CDV persistently infected cell line. RESULTS: The cytoplasm of INB-positive astrocytes expressed elevated 72 kd HSP characteristic of the cellular stress response; INB contained 72 kd HSP and the major CDV nucleocapsid protein (i.e., N). Intranuclear inclusion bodies did not stain positively for the CDV nucleocapsid phosphoprotein nor was intranuclear N protein observed in the absence of nuclear or elevated cytoplasmic 72 kd HSP. In the persistently infected cell line, induction of the cellular stress response elevated 72 kd HSP and produced translocation of the CDV N protein to the nucleus from its normal location in the cytoplasm of unstressed infected cells. As observed in vivo, the transport was specific to N and was correlated to the induction of complex nuclear bodies. The latter was documented by transmission electron microscopy, where complex nuclear bodies formed in shocked infected cells, but not shocked uninfected cells or nonshocked infected cells. CONCLUSIONS: CDV infection in vivo induces the cellular stress response. Paradoxically, this normally protective cellular response mediates redistribution of viral N protein from the cytoplasm into infected cell nuclei, which is the likely basis for complex nuclear body formation and a unique form of virus-induced cytopathic effect.

Animals↗

Intranuclear inclusions in paramyxovirus-induced encephalitis: evidence for altered nuclear body differentiation.

Intranuclear inclusion bodies (INB) are frequently encountered in viral infections, where they are thought to be accumulations of viral particles. However, for RNA viruses replicating in the cytoplasm, this compartmentalization represents a paradox not consistent with the viral replication cycle. To define the basis for intranuclear paramyxoviral inclusion bodies in astrocytes, natural cases of canine distemper virus subacute encephalitis were examined by light and transmission electron microscopy, and by quantitative confocal immunofluorescence microscopy. Although INB were viral antigen positive, they were not composed of structurally recognizable paramyxoviral nucleocapsids. The structural basis for the INB was instead viral antigen-associated forms of nucleolar development known as nuclear bodies. Three variants of the light microscopic Cowdry type A INB were complex nuclear bodies, giant beaded nuclear bodies (sphaeridia), and nuclear body-associated granulofilamentous matrices. In the latter, the granulofilamentous matrix frequently filled the nucleus, resulting in a fourth morphological INB variant, and was associated with morphological evidence of nuclear degeneration. These findings suggest a novel mechanism of virus-induced cytopathology whereby intranuclear viral protein exerts deleterious effects upon nucleolar differentiation in infected cells and hence altered host cell RNA metabolism.

Animals↗

Replication of porcine enteric adenoviruses in vivo.

The replication of an enteropathogenic porcine adenovirus in the intestinal epithelial cells of naturally and experimentally piglets has been studied by transmission electron microscopy (TEM) and by immunoperoxidase (Ip) staining of paraffin sections. Three types of intranuclear inclusion bodies were observed. Viral particles appeared to be assembled from electron dense crescents which seemed to originate from type II intranuclear inclusion bodies. Virus accumulated in the nucleus of infected cells. It formed paracrystalline arrays in the electron dense centre of the nucleus but was dispersed in the peripheral electron translucent zone. Virus was released from the cells after rupture of the nuclear and plasma membranes. The results are compared with published data on the replication of adenoviruses in cell cultures.

Adenoviridae↗

Sudden death in young dogs with myocarditis caused by parvovirus.

Sudden death of pups in the 4- to 6-week age range has recently been occurring in western Canada as a result of severe, primary, nonsuppurative myocarditis. At necropsy, the prominent macroscopic lesion was pulmonary edema, and microscopically, characteristic intranuclear inclusion bodies were found within cardiac myofibers in association with myocarditis. Ultrastructurally, numerous small particles resembling parvoviruses were found within the intranuclear inclusion bodies, which were positive by direct fluorescent antibody test for canine parvovirus. Of three pups inoculated with homogenate from affected myocardium, one developed lesions resembling canine parvoviral enteritis.

Animals↗

Avian adenovirus isolated from pigeons affected with inclusion body hepatitis.

Avian adenoviruses were isolated from two pigeons affected with inclusion body hepatitis (IBH) by using chicken embryo liver cell cultures. One of the isolates, designated strain S-PL1, replicated in the cell nuclei forming intranuclear inclusion bodies, showed adenovirus-like morphology by electron microscopy, and cross-reacted serologically with strain SR-48 known as serotype 2 of fowl adenovirus. The strain S-PL1 killed day-old chicks by subcutaneous inoculation, and its 50% chicken lethal dose was 10(3.8) plaque forming units per bird. Severe lesions characterized with IBH and pancreatitis, were produced in chicks inoculated with the virus. Intranuclear inclusion bodies were also recognized in the liver, pancreas, kidney, proventriculus, small intestine, and caecum. By indirect immunofluorescence test, intranuclear viral antigens were detected in the liver, pancreas and other tissues.

Adenoviridae↗

An outbreak of adenoviral infection in inland bearded dragons (Pogona vitticeps) coinfected with dependovirus and coccidial protozoa (Isospora sp.).

Thirty of 200 (15%) hatchling inland bearded dragons were found dead after a short period (48 hours) of weakness and lethargy. The most common clinical signs were head tilt and circling. Six bearded dragons with neurological signs were euthanized, and postmortem examination revealed no gross abnormalities. Microscopically, severe, randomly distributed hepatocellular necrosis with large basophilic intranuclear inclusion bodies in numerous hepatocytes was noted. Small-intestinal enterocytes contained intracytoplasmic coccidial protozoa (Isospora sp.) and occasional enterocytes had basophilic intranuclear inclusion bodies. Transmission electron microscopy revealed both 80- and 20-nm-diameter viral particles, which were consistent with adenoviruses and dependoviruses, respectively. Adenoviral outbreaks in groups of animals are uncommon. An adverse synergistic effect of the coccidiosis with the adenoviral infection may have played a critical role in the high morbidity and mortality in this case.

Adenoviridae Infections↗

Falcon adenovirus infection in breeding Taita falcons (Falco fasciinucha).

Four female and 3 male Taita falcons (Falco fasciinucha) out of a breeding colony of 14 Taita falcons (7 pairs) died during the breeding season after showing lethargy and anorexia for 1 to 2 days. All animals were submitted for necropsy. Gross lesions in the female falcons were characterized by anemia secondary to marked hemorrhage into the ovary and oviduct, serofibrinous effusion into the cardioabdominal cavity and serosal petechiae. In addition, marked necrotizing splenitis and pulmonary hemorrhage were present. Histologically, the female falcons had mild necrotizing hepatitis with numerous intranuclear inclusion bodies and necrotizing splenitis with rare inclusion bodies. There were no gross lesions in the male falcons, and the histological lesions were characterized by urate deposition and rare intranuclear inclusion bodies in the renal tubular epithelial cells. Adenoviral particles were found by electron microscopy in the cloacal contents of the female Taita falcons but not in the male falcons. DNA in situ hybridization revealed widespread aviadenoviral nucleic acid within the nuclei of hepatocytes, renal tubular epithelial cells, and adrenal cells in the female falcons but no aviadenoviral nucleic acid in 1 male falcon and only a low quantity of adenoviral nucleic acid in the liver and kidney of another male Taita falcon. PCR amplified aviadenoviral DNA in the liver and intestine of all Taita falcons. The amplicons were sequenced, and the virus was identified as falcon adenovirus. The deaths of the female and male birds were attributed to the aviadenovirus infection.

Adenoviridae Infections↗

[An autopsy case of dermatomyositis associated with interstitial pneumonia probably due to cytomegalovirus infection].

An autopsy case of dermatomyositis (DM) associated with interstitial pneumonia probably due to cytomegalovirus infection is reported. After corticosteroid therapy for 1 month, a 79-year-old man with DM developed acute respiratory failure due to interstitial pneumonia and died in spite of intensive respiratory care. By polymerase chain reaction method (PCR), DNA of cytomegalovirus (CMV) was detected in the bronchoalveolar lavage fluid (BALF). CMV was also detected by the method of conventional virus culture from BALF. These findings suggested that initial infection or reactivation of CMV had occurred in the lungs. The autopsy specimen revealed the findings of interstitial pneumonia compatible with CMV pneumonitis, but without the presence of intranuclear inclusion bodies. Although the present case of interstitial pneumonia should not strictly be diagnosed as definite CMV pneumonitis without the presence of intranuclear inclusion bodies in the lung tissue, initial infection or reactivation of CMV in the lungs may have contributed to the pathogenesis of interstitial pneumonia. In other cases of collagen vascular disease associated with interstitial pneumonia, CMV or other viruses may contribute to the pathogenesis of interstitial pneumonia.

Aged↗

Intranuclear aggregation of nonexpanded ataxin-3 in marinesco bodies of the nonhuman primate substantia nigra.

Marinesco bodies (MB) are intranuclear inclusion bodies predominantly found in melanin-pigmented neurons of the substantia nigra. MB are demonstrable not only in humans but also in nonhuman primates. In the present study MB of aged rhesus monkeys (Macaca mulatta; n = 15; mean age 16 years) and aged baboons (Papio anubis; n = 13; mean age 25 years) were examined immunohistochemically. MB were found to be immunoreactive for ubiquitin, a protein involved in initiation of proteasome-mediated proteolysis. We also demonstrate that MB in monkeys are intensely immunoreactive for the protein ataxin-3 as detected by using two monoclonal anti-ataxin-3 antibodies (1H9 and 2B6). The abnormally expanded form of this polyglutamine protein is known to be causally involved in spinocerebellar ataxia type 3 or Machado-Joseph disease. The monoclonal antibody 1C2 was employed to examine whether ataxin-3 in MB in monkeys contains such an abnormally expanded polyglutamine stretch. MB were consistently 1C2-immunonegative, indicating that they are composed of normal wild-type ataxin-3. In conclusion MB in nonhuman primates permit experimental examination of mechanisms involved in transnuclear localization, intranuclear aggregation, and ubiquitination of nonexpanded polyglutamine proteins.

Aging↗

Viral hepatitis in domestic geese in Saskatchewan.

Up to 25% mortality occurred in goslings between 8 and 28 days of age in three sequential hatches from a closed breeder flock on a single farm. The birds died suddenly with minor ascites, subcutaneous and myocardial hemorrhages, and pale, mottled livers with petechial hemorrhages. Liver necrosis associated with intranuclear inclusion bodies was seen on histology. Virus particles were found on examination of the inclusion bodies with an electron microscope. Liver homogenates caused variable mortality 7 to 17 days postinoculation in goose embryos, some of which had hepatic necrosis and intranuclear inclusion bodies. Experimental goslings inoculated with material from these infected embryos died from hepatitis.

Animals↗

Necrotizing pancreatitis and gizzard erosion associated with adenovirus infection in chickens.

Cases of focal necrotic pancreatitis and gizzard erosion in chickens are reported. Intranuclear inclusion bodies were seen in necrotic pancreatic acinar cells and necrotic epithelial cells of the gizzard, and electron microscopy demonstrated virus particles in affected gizzard epithelium. Adenovirus antigens were detected immunohistochemically in these intranuclear inclusion bodies. These findings suggest that the necrotizing pancreatitis and gizzard erosion were associated with adenovirus infection.

Adenoviridae Infections↗

Granular nuclear inclusion body disease: fine structure of tibial muscle and sural nerve.

Fine granular (hyaline) intranuclear inclusion bodies were found in perivascular cells of a muscle and a sural nerve biopsy from a 32-year-old woman with slowly progressive motor disturbances. The hyaline nuclear inclusion bodies could be distinguished from other intranuclear hyaline inclusions by their granularity, the size of the granules (approximately 5-15 nm), and the positive iron staining reaction. They were not seen in muscle fibers or Schwann cells. Because of these apparently pathognomonic structural features the patient appears to present a condition that has not been described before.

Adult↗

Histopathology of feline panleukopenia in domestic cats.

Histopathological observations were carried out on 17 domestic cats naturally affected with feline panleukopenia. Principal lesions were found in the intestine, bone marrow, and lymphoid organs. Intestinal lesions were characterized by degenerative changes accompanied by the appearance of intranuclear inclusion bodies in the epithelial cells of the crypts. In contrast to the crypts, the villi were seldom involved. Hypoplasia, parenchymal degeneration, and activation of the reticuloendothelial system were observed in the bone marrow and lymphoid organs. Intranuclear inclusion bodies were found occasionally also in the reticular and parenchymal cells of the bone marrow, lymphoid organs, liver, adrenals, and pancreas. Most of the inclusion bodies were amphophilic when stained with hematoxylin and eosin and occupied the whole area of the nucleus without producing any zone of clear halo. While cells bearing inclusion bodies underwent degenerative changes constantly in the intestinal crypts, the formation of inclusion body was not accompanied by the degeneration of corresponding cells in any other organ. Pathological changes as mentioned above were considered to be closely related to the systemic infection of feline panleukopenia virus.

Adrenal Glands↗

Giant cell pneumonia: light microscopy, immunohistochemical, and ultrastructural study of an autopsy case.

An autopsy case of measles giant cell pneumonia with intranuclear inclusion bodies is reported. This case of giant cell pneumonia was studied by light microscopy and immunohistochemistry using monoclonal and polyclonal antibody to measles and by electron microscopy (EM). Light microscopic examination showed multinucleated epithelial giant cells with intranuclear and intracytoplasmic inclusions. The giant cells contained prominent, sharply marginated, eosinophilic intranuclear inclusions typical of classic measles pneumonia. Presence of measles antigen was confirmed using both monoclonal and polyclonal antibodies by peroxidase antiperoxidase method. Monoclonal antibody stained positively for intracytoplasmic and intranuclear inclusions. Electron microscopic examination of lung tissue showed intranuclear inclusions of filamentous or worm like nucleocapsid materials in multinucleated epithelial giant cells. The results suggest that this is a case of measles giant cell pneumonia and the intranuclear inclusion bodies are measles viral particles.

Autopsy↗

Fatal herpesvirus tamarinus infection in cotton-topped marmosets (Saguinus oedipus).

Fatal herpesvirus tamarinus infection was observed in cotton-topped marmosets (Saguinus oedipus) imported from South America via the United States on August 26, 1976. In addition to the lesions hitherto reported in herpesvirus tamarinus infection, severe degenerative and necrotic changes of ganglion cells were recognized with intranuclear inclusion bodies in the plexus of the digestive tract and the sympathetic nerves and their ganglions in the abdominal cavity. Inflammatory or regressive changes were also noted in the central nervous system. A large number of basophilic or eosinophilic intranuclear inclusion bodies frequently recognized in multinucleated giant cells were observed in various organs and tissues, and they showed different shapes at the electron microscopic level. Morphological findings indicated that herpesvirus tamarinus infection seemed to be similar to herpes simplex virus infection in man. The findings of the susceptibility of a variety of cell cultures to the virus isolate serologically identified as herpesvirus tamarinus and physicochemical characteristics of the virus isolate were in general agreement with the findings of herpesvirus tamarinus already reported by previous workers.

Animals↗

Pathology of bovine abortion and newborn calf death caused by dual infection with Chlamydia psittaci and infectious bovine rhinotracheitis virus.

Nine aborted fetuses and one newborn calf, diagnosed as Chlamydia psittaci (C. psittaci) infection, were pathologically examined. The characteristic lesions in the liver were focal necrosis in 9 aborted fetuses and granulomatous necrotic foci in the newborn calf. Moderate numbers of intranuclear inclusion bodies were found in necrotic foci of the liver, spleen, thymus, lymph nodes, adrenal gland, kidney, lung and forestomach. Immunohistologically, a small number of C. psittaci antigens was demonstrated in necrotic foci of the liver and correlated with distribution of elementary bodies. Moderate numbers of infectious bovine rhinotracheitis (IBR) virus antigens were also detected in degenerating and necrotizing parenchymal cells in various organs and correlated with distribution of intranuclear inclusion bodies. Thus, these aborted bovine fetuses and newborn calf were interpreted as being dually infected with C. psittaci and IBR virus during pregnancy.

Abortion, Veterinary↗