An animal model for copper-associated cirrhosis in infancy

Aston, Nicola S.; Morris, Pauline A.; Tanner, M S; Variend, S.

doi:10.1002/(sici)1096-9896(1998100)186:2<215::aid-path145>3.0.co;2-c

Cited by 11 publications

(8 citation statements)

References 22 publications

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“…10 In the case of the Mallory body, the intermediate filaments within the inclusions have been identified as high-and low-molecular-mass cytokeratin filaments. 2,8,9,11,15 Ultrastructurally similar aggregates of vimentin and neurofilaments have been identified in other variants of intracytoplasmic nonviral inclusion bodies. 20 The lack of affinity of anti-cytokeratin, -neurofilament, and -vimentin antibodies for IBD inclusions suggests that they do not contain intermediate filament proteins.…”

Section: Discussionmentioning

confidence: 94%

“… 10 11 20 Intermediate filaments are cytoskeletal components that range from 6 to 11 μm in diameter and include vimentin, cytokeratins, tonofilaments, and neurofilaments. 10 In the case of the Mallory body, the intermediate filaments within the inclusions have been identified as high- and low-molecular-mass cytokeratin filaments 2 8 9 11 15 Ultrastructurally similar aggregates of vimentin and neurofilaments have been identified in other variants of intracytoplasmic nonviral inclusion bodies.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the lack of an established casual relationship between the virus and the inclusion body, the current recommendation is to euthanatize all boid snakes exhibiting signs compatible with IBD when the characteristic inclusion bodies in biopsy specimens are revealed by light microscopy. 26 Because of the morphologic and histochemical similarities between IBD inclusions and other types of nonviral intracytoplasmic bodies, we decided to study and better characterize the IBD virus (IBDV)-associated inclusions 2 7–9, 11 15 25 26 The objectives of the study were to examine the relationship between the retrovirus-like agent and its associated nonviral inclusion bodies and to identify and characterize the material within the inclusion bodies.…”

mentioning

confidence: 99%

“…7,9,11,15,20,23 Nonviral inclusions characterized as amorphous intracytoplasmic eosinophilic hyaline bodies have been demonstrated in human and animal tissues afflicted with a diverse array of disease conditions, including alcoholism, neoplasia, morbid obesity, Indian childhood cirrhosis, pyrrolizidine alkaloid and copper exposure, and prolonged griseofulvin treatment. 2,[7][8][9]11,15,26 These inclusion bodies represent intracytoplasmic aggregates of various intermediate filaments, including cytokeratins, vimentin, and neurofilaments. 8,10,11,20 In some cases, the intermediate filaments within nonmembrane-bound inclusions were thickened by a diffuse coating of ubiqutin.…”

mentioning

confidence: 99%

“…26 Because of the morphologic and histochemical similarities between IBD inclusions and other types of nonviral intracytoplasmic bodies, we decided to study and better characterize the IBD virus (IBDV)-associated inclusions. 2,[7][8][9]11,15,25,26 The objectives of the study were to examine the relationship between the retrovirus-like agent and its associated nonviral inclusion bodies and to identify and characterize the material within the inclusion bodies.…”

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confidence: 99%

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Isolation and Characterization of an Antigenically Distinct 68- kd Protein from Nonviral Intracytoplasmic Inclusions in Boa Constrictors Chronically Infected with the Inclusion Body Disease Virus (IBDV: Retroviridae)

et al. 2000

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Abstract.The relationship between a retroviral infection and the development of nonviral intracytoplasmic inclusion bodies was studied in a Boa constrictor model. Twelve juvenile age-and size-matched inclusion body disease (IBD)-negative boas were randomly divided into three groups. Each group was inoculated intraperitoneally with 1 ml of an IBD virus (IBDV)-infected liver homogenate or 1 ml of normal boa liver homogenate (sham-inoculated control) or was left untreated. All boas were monitored for development of IBD by daily examination and serial liver biopsy over 1 year. The 4 IBDV-inoculated boas became IBDV and inclusion positive by 10 weeks postinoculation. The average size and density of inclusion bodies increased with the duration of infection. Ultrastructurally, inclusion bodies Ͻ2 m in diameter consisted of intracytoplasmic aggregates of granular electron-dense material that were not membrane limited. Larger inclusions (3-6 m in diameter) were characterized as membrane-bound aggregates of amorphous to granular electron-dense material admixed with membranelike fragments. The sham-inoculated and untreated control snakes did not become inclusion or IBDV positive. Direct comparison of the protein electrophoretograms of IBDV-infected and normal boa tissues demonstrated a prominent 68-kd protein band unique to infected inclusion-positive tissues. Monoclonal antibodies directed against the 68-kd protein band specifically labeled inclusion bodies. The results of this study demonstrate that IBD inclusions represent an intracytoplasmic accumulation of an antigenically distinct IBDV-associated protein.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Isolation and Characterization of an Antigenically Distinct 68- kd Protein from Nonviral Intracytoplasmic Inclusions in Boa Constrictors Chronically Infected with the Inclusion Body Disease Virus (IBDV: Retroviridae)

et al. 2000

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Copper-associated liver disease in North Ronaldsay sheep: a possible animal model for non-Wilsonian hepatic copper toxicosis of infancy and childhood

Haywood

Müller

Müller³

et al. 2001

J. Pathol.

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Indian childhood cirrhosis (ICC), endemic Tyrolean infantile cirrhosis (ETIC) and idiopathic copper toxicosis (ICT), are clinically and pathologically indistinguishable liver disorders of infants and young children linked with exogenous copper and with increasing evidence for a genetic predisposition. North Ronaldsay sheep are a primitive breed which have adapted to a copper impoverished environment (<5 ppm) and display an abnormal sensitivity to copper poisoning when transferred to a copper replete (11 ppm) habitat. The aetiological parallels prompted a study of copper-associated liver disease in North Ronaldsay sheep (RCT) to see if the pathology could contribute to the understanding of the childhood disorder. A retrospective study was performed in which the livers of 22 mainland-bred North Ronaldsay sheep were compared with three island-bred sheep and categorized for liver copper content and pathomorphology. It was found that all the mainland sheep had accumulated liver copper (>300 microg/g), in contrast to the island sheep, although 10 sheep with increased liver copper (mean 600 SD 270 microg/g) showed no evidence of liver damage. A further 10 sheep with liver copper (mean 1276 SD 508 microg/g) exhibited periportal to panlobular histochemical copper retention, a periportal and/or panlobular pericellular fibrosis, a mixed inflammatory infiltrate and cholangioplasia. Steatosis was absent and regeneration was in abeyance. Finally, two sheep (liver copper >2000 microg/g) had a more active hepatitis with a florid pericellular, panlobular fibrosis and cirrhosis. Electron microscopy identified large numbers of collagen-producing hepatic stellate (Ito) cells in periportal regions. The pathological findings were sufficiently reminiscent of ICC, ETIC and ICT to warrant further exploration of RCT as a putative animal model. The North Ronaldsay sheep liver may be a useful tool for the investigation of copper-induced fibrogenesis.

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Copper Related Liver Disease in Young Children

Tanner

1999

Metals and Genetics

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An animal model for copper-associated cirrhosis in infancy

Cited by 11 publications

References 22 publications

Isolation and Characterization of an Antigenically Distinct 68- kd Protein from Nonviral Intracytoplasmic Inclusions in Boa Constrictors Chronically Infected with the Inclusion Body Disease Virus (IBDV: Retroviridae)

Isolation and Characterization of an Antigenically Distinct 68- kd Protein from Nonviral Intracytoplasmic Inclusions in Boa Constrictors Chronically Infected with the Inclusion Body Disease Virus (IBDV: Retroviridae)

Copper-associated liver disease in North Ronaldsay sheep: a possible animal model for non-Wilsonian hepatic copper toxicosis of infancy and childhood

Copper Related Liver Disease in Young Children

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