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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunopathogenesis of AIDS-associated hepatitis was explored in the SIV/rhesus monkey model. The livers of SIV-infected monkeys showed a mild hepatitis, with a predominantly CD8+ T lymphocyte infiltration in the periportal fields and sinusoids. These liver-associated CD8+ T cells were comprised of a high percentage of SIV-specific CTL as defined by MHC class I/Gag peptide tetramer binding and Gag peptide epitope-specific lytic activity. There was insufficient viral replication in these livers to account for attracting this large number of functional virus-specific CTL to the liver. There was also no evidence that the predominant population of CTL were functionally end-stage cells trapped in the liver and destined to undergo apoptotic cell death in that organ. Interestingly, we noted that liver tetramer-binding cells showed an increased expression of CD62L, an adhesion molecule usually only rarely expressed on tetramer-binding cells. This observation suggests that the expression of specific adhesion molecules by CTL might facilitate the capture of these cells in the liver. These results demonstrate that functional SIV-specific CD8+ T cells are present in large numbers in the liver of chronically SIV-infected monkeys. Thus, the liver may be a trap for virus-specific cytotoxic T cells.
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PMID:Simian immunodeficiency virus (SIV)-specific CTL are present in large numbers in livers of SIV-infected rhesus monkeys. 1082 Feb 85

The rhesus macaque ( Macaca mulatta) has become a popular animal model for several human infectious diseases, such as HIV (modeled by SIV infection), hepatitis, and malaria. Investigation of T-cell responses in experimental infectious diseases in rhesus macaques has benefited from an expanding understanding of the diversity of macaque MHC class I heavy chains and the restriction of antigen presentation by macaque class I molecules. Here we add to this understanding with the first nucleotide sequences of M. mulatta beta(2)-microglobulin (beta(2)m) mRNA, including a portion of the 3'-untranslated region (3'UTR). In pairwise comparison, the beta(2)m protein of M. mulatta differs from human and chimpanzee beta(2)m by nine amino-acid substitutions (92% identity), and from Macaca fascicularis by one amino-acid difference in the signal peptide region (99% identity). Allelic variations were identified at one site in the 3'UTR. A structural analysis of human or chimpanzee beta(2)m and M. mulatta beta(2)m suggests that the differences cluster in three solvent-exposed clusters and do not involve contacts with the class I heavy chain. We predict that human and macaque beta(2)m should bind interchangeably with the class I heavy chains of the other species, and show that four M. mulatta class I alleles form cell surface complexes with human beta(2)m. Further, we predict that W6/32 (a monoclonal antibody that recognizes a combined epitope of some class I heavy chains and beta(2)m with a subtle species dependence) should bind similarly human or macaque class I molecules that are bound with beta(2)m of either species, supported by evidence of recognition of both heterologous and homologous complexes of macaque class I heavy chains. Our findings contribute to the growing understanding of rhesus macaque histocompatibility antigens and antigen presentation, and to the phylogeny of beta(2)m in primates.
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PMID:Sequence of beta(2)-microglobulin from rhesus macaque ( Macaca mulatta) includes an allelic variation in the 3'-untranslated region. 1496 20

We previously compared the expression of several human factor VIII (fVIII) transgene variants and demonstrated the superior expression properties of B domain-deleted porcine fVIII. Subsequently, a hybrid human/porcine fVIII molecule (HP-fVIII) comprising 91% human amino-acid sequence was engineered to maintain the high-expression characteristics of porcine fVIII. The bioengineered construct then was used effectively to treat knockout mice with hemophilia A. In the current study, we focused on optimizing self-inactivating (SIN) lentiviral vector systems by analyzing the efficacy of various lentiviral components in terms of virus production, transduction efficiency and transgene expression. Specifically, three parameters were evaluated: (1) the woodchuck hepatitis post-transcriptional regulatory element (WPRE), (2) HIV versus SIV viral vector systems and (3) various internal promoters. The inclusion of a WPRE sequence had negligible effects on viral production and HP-fVIII expression. HIV and SIV vectors were compared and found to be similar with respect to transduction efficiency in both K562s and HEK-293T cells. However, there was an enhanced expression of HP-fVIII by the SIV system, which was evident in both K562 and BHK-M cell lines. To further compare expression of HP-fVIII from an SIV-based lentiviral system, we constructed expression vectors containing the high expression transgene and a human elongation factor-1 alpha, cytomegalovirus (CMV) or phosphoglycerate kinase promoter. Expression was significantly greater from the CMV promoter, which also yielded therapeutic levels of HP-fVIII in hemophilia A mice. Based on these studies, an optimized vector contains the HP-fVIII transgene driven by a CMV internal promoter within a SIV-based lentiviral backbone lacking a WPRE.
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PMID:Generation of an optimized lentiviral vector encoding a high-expression factor VIII transgene for gene therapy of hemophilia A. 2299 97

Two cases of clinical disease associated with extraintestinal Campylobacter infection were recently encountered in rhesus macaques (Macaca mulatta). The first case was that of a 3-y-old, male, rhesus macaque experimentally infected with SIV, who presented with abdominal pain and a midabdominal mass and was euthanized. Pathology findings included an abscess within the median liver lobe, fibrinopurulent peritonitis, and intestinal serositis with isolation of Campylobacter fetus from the blood, liver, and the hepatic abscess. The second case was that of a 1-mo-old, female, rhesus macaque who died with no apparent history of illness. Gross pathology findings included thin body condition and diarrheic staining of the perineum; histologically, acute multifocal hepatitis with intralesional bacteria was noted. Campylobacter coli was isolated from the liver and colon. Extraintestinal Campylobacter infection is uncommon in humans, usually occurring in immunocompromised subjects and most commonly manifesting as bacteremia. Extraintestinal Campylobacter infections in animals are rare but have been associated with bacteremia and cholecystitis. The macaques presented here were either immunocompromised due to SIV infection (case 1) or more vulnerable due to young age (case 2). These factors likely contributed to the extraintestinal spread of Campylobacter.
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PMID:Extraintestinal campylobacteriosis in rhesus macaques (Macaca mulatta). 2552 31