Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenoviruses are ubiquitous organisms but only infrequently have been implicated as a cause of hepatitis and rarely as a cause of fatal disease. A fatal case of disseminated adenovirus serotype 31 infection is described. It occurred in a patient with severe combined immunodeficiency who received a fetal liver transplant and subsequently developed massive hepatic necrosis. To the best knowledge of the authors, this is the first reported case of disseminated disease due to serotype 31.
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PMID:Disseminated adenovirus serotype 31 infection in an immunocompromised host. 609 98

An in vivo murine model for immunodeficiency of both B and T cells is produced by continuous intraperitoneal infusion of 2'-deoxycoformycin (DCF), a specific tightly binding inhibitor of adenosine deaminase (ADase; adenosine aminohydrolase, EC 3.5.4.4). After DCF infusion, ADase of thymus, spleen, and lymph nodes was inhibited to varying degrees ranging from 57% to 100%. Immunodeficiency under these conditions was indicated by: (i) a striking decrease in lymphocyte response to the T-cell mitogens concanavalin A and phytohemagglutinin; (ii) an impairment of delayed hypersensitivity measured by the footpad reaction; (iii) a decrease in antibody production measured in both in vivo and in vitro plaque-forming cell assay; (iv) a significant prolongation of mouse skin allograft survival after transplantation into the C57BL/6J (H-2b) strain of skin from BALB/c (H-2d) mice; and (v) a marked lymphopenia. Histological examination indicated lymphoid degeneration in the thymus, lymph nodes, and spleen with no alterations in other tissues including bone marrow, kidney, lung, gastrointestinal tract, and liver except for the occurrence of hepatitis. A decrease in the number of Thy-1-positive cells in both spleen and lymph nodes further supported the fact of cytotoxicity of DCF to T cells. Anorexia and weight loss were observed within 5 days of continuous DCF infusion at 0.4 mg/kg body weight per day. These data indicate that this method provides an experimental model for future studies on the biochemical mechanisms responsible for the genetically determined severe combined immunodeficiency disease in man.
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PMID:Animal model for immune dysfunction associated with adenosine deaminase deficiency. 696 8

Review of liver biopsy or autopsy material from 33 patients with severe combined immunodeficiency or combined immunodeficiency and four patients with DiGeorge syndrome revealed a wide range of hepatic pathology. The most common abnormality was graft-versus-host disease (16 patients), followed by viral infection (4 patients had adenovirus hepatitis, 3 had cytomegalovirus hepatitis). Centrilobular fibrosis with or without veno-occlusive disease was seen in five patients. Three patients had nonspecific hepatitis, four had changes attributed to total parenteral nutrition, and two had lymphoproliferative disorders involving the liver. Both patients with lymphoproliferative disorders had received transplants. Two patients had resolving necrosis probably secondary to non-A, non-B hepatitis. One had atypical mycobacterial infection. Hemosiderosis was a common nonspecific abnormality, seen in nine patients. All patients with hepatic graft-versus-host disease had received transplants or nonirradiated blood products. Hepatic graft-versus-host disease varied in severity from hepatic necrosis with destruction of both large and small bile ducts in a transfusion-associated case to subtle damage to interlobular bile ducts. Even minimal bile duct changes correlated with the clinical impression of graft-versus-host disease in these patients. Late chronic graft-versus-host disease was not seen in any patient, although acute graft-versus-host disease sometimes occurred late after transplant.
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PMID:Pathology of the liver in severe combined immunodeficiency and DiGeorge syndrome. 837 33

Human hepatitis delta virus (HDV), obtained from the serum of an experimentally infected woodchuck, was injected into either the peritoneal cavity or the tail vein of both adult CB17 mice and mice with a severe combined immunodeficiency (CB17-scid mice). Three lines of evidence indicated that the virus was able to reach the liver and infect hepatocytes: (i) the amount of HDV genomic RNA detected in the liver by Northern (RNA) analysis increased during the first 5 to 10 days postinoculation, reaching a peak that was about threefold the amount in the original inoculum; (ii) also detected in the liver was the viral antigenomic RNA, which is complementary to the genomic RNA found in virions, and is diagnostic for virus replication; and (iii) by immunoperoxidase staining of liver sections, the delta antigen was detected in the nuclei of scattered cells identifiable as hepatocytes. In all of the mice, clearance of the infection occurred between 10 and 20 days after inoculation. The half-life for clearance was about 3 days in CB17-scid mice, indicating that clearance of infection did not involve a T- and B-cell-dependent immune response. Cell-to-cell spread of the initial infection was not detected. One possible interpretation of our results is that HDV infection of hepatocytes is directly cytopathic. Also, the results imply that chronic infection of the liver in humans may require continuous spread of virus within the liver. Alternatively, HDV in the absence of helper virus may be unable to cause a chronic infection of hepatocytes in vivo.
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PMID:Experimental transmission of human hepatitis delta virus to the laboratory mouse. 849 56

Adenosine deaminase (ADA) deficiency typically causes severe combined immunodeficiency (SCID) in infants. We report metabolic, immunologic, and genetic findings in two ADA-deficient adults with distinct phenotypes. Patient no. 1 (39 years of age) had combined immunodeficiency. She had frequent infections, lymphopenia, and recurrent hepatitis as a child but did relatively well in her second and third decades. Then she developed chronic sinopulmonary infections, including tuberculosis, and hepatobiliary disease; she died of viral leukoencephalopathy at 40 years of age. Patient no. 2, a healthy 28-year-old man with normal immune function, was identified after his niece died of SCID. Both patients lacked erythrocyte ADA activity but had only modestly elevated deoxyadenosine nucleotides. Both were heteroallelic for missense mutations: patient no. 1, G216R and P126Q (novel); patient no. 2, R101Q and A215T. Three of these mutations eliminated ADA activity, but A215T reduced activity by only 85%. Owing to a single nucleotide change in the middle of exon 7, A215T also appeared to induce exon 7 skipping. ADA deficiency is treatable and should be considered in older patients with unexplained lymphopenia and immune deficiency, who may also manifest autoimmunity or unexplained hepatobiliary disease. Metabolic status and genotype may help in assessing prognosis of more mildly affected patients.
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PMID:Adenosine deaminase deficiency in adults. 910 4

Under certain conditions, C57BL/6 mice persistently infected with mouse hepatitis virus strain JHM (MHV-JHM) develop clinical disease and histological evidence of demyelination several weeks after inoculation with virus. In a previous report, we showed that mutations in the RNA encoding an immunodominant CD8 T-cell epitope within the surface glycoprotein (epitope S-510-518) were present in all persistently infected animals and that these mutations abrogated recognition by virus-specific cytotoxic T cells (CTLs) in direct ex vivo cytotoxicity assays. To obtain further evidence that these mutations were necessary for the development of clinical disease, the temporal course of their appearance was determined. Mutations in the epitope were identified by 10 to 12 days after inoculation, and in some mice, virus containing mutated epitope was the dominant species detected by 15 days. In addition, most mice that remain asymptomatic at 80 days after inoculation, a time after which clinical disease almost never develops, were infected with only wild-type virus. Finally, analysis of virus isolated from mice with severe combined immunodeficiency (SCID) revealed the presence only of wild-type epitope S-510-518. These results, by showing that mutations are not selected in SCID mice and occur at early times after inoculation in C57BL/6 mice, support the view that they result from immune pressure and contribute to virus persistence and demyelination in mice infected persistently with MHV-JHM.
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PMID:Cytotoxic T-cell-resistant variants arise at early times after infection in C57BL/6 but not in SCID mice infected with a neurotropic coronavirus. 931 46

A new species of Mycoplasma, M. volis, was isolated from the respiratory tract of clinically normal field-trapped prairie voles (Microtus ochrogaster) that were to be housed in close proximity to other rodents. To determine the pathogenic potential of the new mycoplasmal isolate, three groups of rodents (Sprague Dawley rats, BALB/c mice, and severe combined immunodeficient [SCID] mice) were intranasally inoculated with 2 x 10(8) color-changing units (CCU) of M. volis and were observed for 4 to 6 weeks. Experimental animals did not manifest clinical signs of disease; however, one experimental SCID mouse was euthanized 5 days after inoculation because of a severe circling disorder. Lung lesions in experimental SD rats ranged from mild to severe bronchial-associated lymphoid tissue (BALT) hyperplasia. Lung lesions in BALB/c and SCID mice ranged from no lesions to mild pneumonia. We were able to isolate M. volis from some control mice, none of which had lung lesions. All mice were seronegative for Sendai virus, mouse hepatitis virus, and M. pulmonis. All immunocompetent experimental animals (BALB/c mice and Sprague Dawley rats) were seropositive for M. volis. All immunocompetent control animals and SCID mice were seronegative for M. volis. Our data suggest that M. volis is capable of causing microscopic lesions and seroconversion in rats and mice, and therefore these rodents should not be housed in close proximity to voles.
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PMID:Pathogenicity of Mycoplasma volis in mice and rats. 951 88

Hepatitis, proliferative typhlitis, and colitis were characterized in young adult and older SCID/NCr mice naturally infected with Helicobacter hepaticus. Liver lesions consisted of Kupffer, Ito, and oval cell hyperplasia along with multifocal to coalescing coagulative hepatocyte necrosis. Numerous Warthin-Starry-positive bacteria were observed in the parenchyma, and there were minimal to mild accumulations of monocytic cells and neutrophils. Proliferative typhlitis was characterized by moderate to marked mucosal epithelial cell hyperplasia with mild monocytic and neutrophilic infiltration. Minimal to mild colitis with mucosal epithelial cell hyperplasia of the colon was most marked in older mice. Comparable gastrointestinal lesions were not observed in uninfected control SCID/NCr mice. H. hepaticus was cultured from fetal viscera of 2 of 11 pups sampled late in gestation from infected SCID/NCr females, suggesting transplacental infection of H. hepaticus. As expected, most of the naturally infected SCID/NCr mice had no serum immunoglobulin G response against H. hepaticus. These findings contrast with those in infected immunocompetent A/JCr mice, which develop a significant immune response to H. hepaticus associated with prominent multifocal mononuclear cell infiltrates in the liver, with only rare bacteria observable at the periphery of inflammatory foci or in the biliary canaliculi. The results demonstrate that chronic inflammatory and proliferative lesions simultaneously affecting the liver, cecum, and colon are associated with natural infection of SCID/NCr mice with H. hepaticus and that lesions are progressive with age. Concurrent infection with H. hepaticus may confound studies that have been attributed to similar lesions due to other experimental manipulations of SCID/NCr mice.
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PMID:SCID/NCr mice naturally infected with Helicobacter hepaticus develop progressive hepatitis, proliferative typhlitis, and colitis. 978 60

Since the first isolation of Helicobacter pylori from humans in 1983, 18 Helicobacter species have been identified during the last decade in domestic and laboratory animals. Several Helicobacter species have been isolated from the gastrointestinal tracts of various mammalian species and birds. Helicobacter hepaticus, H. muridarum, H. bilis, H. rodentium and Flexispira rappini have been isolated from mice. Among these species, only H. hepaticos has been clearly recognized as a pathogen. Indeed, it displays the pathogenic potential to elicit hepatitis in several strains of mice; moreover in A/JCr mice, it is strongly associated with hepatic cancer. Among the five murine helicobacter species, apart from H. hepaticus, F. rappini has not been found associated with lesions, H. muridarum has been observed in gastric glands of mice with chronic gastritis, and H. bilis has been reported in the liver of mice with chronic hepatitis. When associated with H. rodentium, H. bilis is able to induce diarrhea in SCID mice. In no case has pathogenicity of a single species been clearly proven. In rats, H. trogontum and H. muridarum have been isolated from the intestine, without any information concerning their respective pathogenicity. H. cinaedi and H. cholecystus have been identified from the intestine and the gallbladders of hamsters, respectively. The diagnosis of Helicobacter species by polymerase chain reaction (PCR) is a rapid, specific and sensitive technique. One of the most promising diagnostic techniques of these infections seems to be the PCR detection of Helicobacter sp. from feces based on the 16S rRNA sequences, then a restriction enzyme analysis to identify the actual species. Several drug regimens have also been evaluated to eradicate H. hepaticus from mice. Helicobacter infections, particularly H. hepaticus and H. bilis, seem to be widespread in laboratory mouse colonies and have also been detected from commercial breeders.
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PMID:Pathology, diagnosis and epidemiology of the rodent Helicobacter infection. 1009 28

Patients with acquired immune deficiency syndrome (AIDS) and boys with mutations of the CD154 gene (causing congenital X-linked immunodeficiency with hyper-IgM [XHIM]) are susceptible to chronic infections of the biliary tract with Cryptosporidium parvum (CP) that may lead to biliary sclerosis and ultimately to cholangiocarcinoma. To determine whether the CP infection and the consequent immune response contribute independently to this morbidity, we infected mice with severe combined immunodeficiency (SCID) or with disrupted genes for CD154, CD40, or interferon gamma (IFN-gamma) with CP. Even when CP infection persisted for 16 weeks, the SCID mice developed only mild triaditis, without apoptosis of biliary epithelial cells (BEC). Fifty percent of the CD154 knockout mice developed lobular hepatitis with acute and chronic triaditis. The CD40 knockout mice developed marked triaditis, and the IFN-gamma knockouts either succumbed to enteritis or survived to develop marked triaditis, portal fibrosis, biliary sclerosis, necrosis with dilation of duct-like structures within the porta hepatis, and dysplastic changes. CP-infected SCID mice reconstituted with T cells from IFN-gamma knockout donors either developed severe enteritis or survived to develop triaditis, cholangitis, lobular hepatitis with periductular sclerosis, and scarring. Mice with disruptions of both the CD40 and IFN-gamma genes remained infected by CP and developed bile duct and liver disease, but not enteritis. Our results suggest that T-cell cytokines are required for the inflammatory and sclerosing responses to CP infection in immunodeficient animals. The response of immunodeficient mice to CP infection may model at least the initial steps toward the development of sclerosing cholangitis or bile duct cancers in XHIM patients.
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PMID:Liver and bile duct pathology following Cryptosporidium parvum infection of immunodeficient mice. 1038 35


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