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

Thymectomized DBA/2 mice, irradiated with 720 rad/min and reconstituted with syngeneic bone marrow, were treated i.p. with 1 g/kg body weight D-galactosamine-HCl (DGA). Light and electron microscopic changes characteristic of the toxic effect of the agent, such as hepatocellular cytoplasmic inclusions and unicellular necrosis, could be observed but no inflammatory reaction was detectable in the liver. The phagocytic activity of Kupffer cells proved to be unchanged in immunosuppressed animals. Liver regeneration following DGA injury took place in 120 hours exactly as in animals having an intact immune system. The experiments suggested that T-lymphocytes participate in the development of DGA-hepatitis and their absence does not influence the restoration of liver injury. The experimental system described seems to be suitable for separating primary and secondary events and also for studying the role of the immune system in toxic liver injury.
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PMID:D-galactosamine-induced liver injury in immunosuppressed mice. 608 23

ALP activity has been studied during hepatitis (infection) in two genetically controlled mouse strains having different degrees of susceptibility ot MHV3 virus: A/JAX (resistant) and DBA/2 (susceptible). During the 8 days following viral infection we have compared ALP activity in serum and liver homogenates with ALP cytological localization in liver tissue (light and electron microscopy). Firstly, liver ALP activity has been demonstrated in the Disse's spaces, on the membrane of the hepatocytes microvilli whilst serum ALP was still very low. The serum ALP activity begins to increase markedly since the third day in sensitive mice (DBA/2), i.e., when the electron microscopy hepatocytes look very damaged; hepatocytes have lost most of their microvilli; necrotic vesicles, degenerative cytoplasmic organelles, lipid vesicles occurred in numerous hepatocytes. ALP activity has disappeared at the biliary pole of the cells whilst it increased at the vascular pole. Moreover, electron microscopic studies demonstrated that ALP positive cells are exclusively of lymphoid type whereas Kupffer cells remain ALP negative.
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PMID:The alkaline phosphatase activity in DBA/2 and A/JAX mouse strains injected with mouse hepatitis virus 3: a morphological and biochemical comparative study. 608 29

Pre-infection with mouse hepatitis virus (MHV) strains S, 3, or JHM reduced the ability of mice to seroconvert to PVM. Geometric mean antibody titers to PVM among MHV pre-infected mice were lower than those for control mice given only PVM, and dually infected mice seroconverted to PVM later than mice given PVM alone. PVM was not recovered from normally permissive respiratory tract tissues of MHV-S pre-infected mice. Pre-infection of DBA/2 mice with MHV-S compromised the susceptibility of these mice to lethal Sendai virus infection but did not substantially reduce the titers of infectious Sendai virus recovered from the lungs. Serologic responses to Sendai virus and lung Sendai virus titers were similar in Sendai virus-resistant C57BL/6 mice pre-infected or not with MHV-S.
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PMID:Alteration of viral respiratory infections of mice by prior infection with mouse hepatitis virus. 609 62

Several strains of mice were examined for antibody production after intranasal inoculation with a low virulence strain of mouse hepatitis virus (MHV), MHV-NuU. C57BL/6N mice were shown to be high responders in the production of complement fixing (CF) antibody as compared to C3H/HeN, BALB/c-AnN, DBA/2N mice. F1 hybrids B6C3 and BDF1 from C57BL/6N mice, showed CF antibody responses as high as C57BL/6N, suggesting that high responsiveness is genetically controlled. All these mouse strains were able to produce high titred neutralizing antibody to MHV.
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PMID:Differences in antibody production against mouse hepatitis virus (MHV) among mouse strains. 630 37

Cobalt-activated acylase (Co-A) and transaminase activity were determined in the serum of A/Jax, DBA/2 and C3H mice several days after an intraperitoneal injection of 1,000 lethal doses of murine hepatitis virus type 3 (MHV3). A significant rise in the enzyme activity was observed 1 day after the injection, followed by a decrease on day 2. In the case of the genetically resistant A/Jax strain, the Co-A level regularly decreased to reach normal values on days 7-8. On the contrary, among the fully susceptible DBA/2 strain mice (all dead on day 5), a second rise in acylase (Co-A) level was observed on days 3 and 4, much higher than the day-1 values. Among the mice of C3H strain, which is recorded as 'semi-susceptible', some individuals behaved like the susceptible DBA/2. The comparison of serum acylase activity with other liver function tests showed a correlation between Co-A and transaminases (ALT and AST) with C3H and DBA/2 strains, but no correlation with A/JAX resistant strain. gamma-Glutamyltransferase was not detectable in the serum of different strains during the time of experimentations. Our results suggest that Co-A activity correlates with the clinical course, and that Co-A is a sensitive indicator enzyme in the early phase of viral hepatitis.
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PMID:A genetic study of serum levels of cobalt-activated acylase among susceptible, resistant and semiresistant strains of mice with experimental viral hepatitis. 715 76

Genetic susceptibility to toxic chemicals is of major importance but most studies concentrate on candidate genes and searches for unknown susceptibility genes are uncommon. Human sporadic porphyria cutanea tarda is usually precipitated by alcohol, oestrogens, hepatitis viruses, HIV or haemodialysis. The mechanism is not known but there is a role for iron metabolism and an underlying genetic predisposition is suspected. A similar porphyria in humans has also been caused by hexachlorobenzene. These human porphyrias can be modelled in iron-loaded mice exposed to hexachlorobenzene, in which C57BL/10ScSn is a prototype susceptible strain whereas DBA/2 mice are extremely resistant. A search for susceptibility genes was undertaken using complex trait analysis with DNA microsatellite markers of 'high' and 'low' responders from an F2 intercross. Correlation of markers with susceptibility, defined as accumulation of uroporphyrin in the liver, was assessed by chi-squared test for the proportion of C57BL/10ScSn and DBA/2 alleles present. Susceptibility loci on chromosomes 12, 14 and 17 were identified. Further analysis of markers on chromosomes 14 and 17 by MAPMAKER/EXP and MAPMAKER/QTL gave LOD scores of 7.3 and 3.6, respectively. Typing of chromosome 12 for the Ahr gene, using a restriction fragment length polymorphism distinguishing between the b-1 and d alleles, gave significant but not perfect linkage. However, no strong association between alleles or expression of Cyp1a1/2 genes, regulated by Ahr, and susceptibility for porphyria was detected. The results demonstrate that the porphyria induced by hexachlorobenzene in C57BL/10ScSn mice is a complex trait determined by at least three genes, which may be of relevance to susceptibility in the development of sporadic porphyria cutanea tarda and unknown aspects of liver damage.
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PMID:Chromosomal linkage analysis of porphyria in mice induced by hexachlorobenzene-iron synergism: a model of sporadic porphyria cutanea tarda. 991 32

Euphorbia milii (Euphorbiaceae) is a decorative plant used in gardens and living fences. In China, it has also been employed in herbal remedies for hepatitis and abdominal edema. Since E. milii latex--lyophilized or in natura--proved to be a potent plant molluscicide, its toxicity to non-target organisms has been comprehensively studied. Concerns on a possible tumor promoting activity have discouraged its use as a locally-available alternative molluscicide in schistosomiasis control programs. Two in vitro assays (inhibition of metabolic cooperation in V79 cells and Epstein-Barr virus induction in Raji cells) had suggested that E. milii latex contained tumor-promoting substances. This study was undertaken to verify whether the latex acts as a tumor promoter in vivo as well. A single dose of the initiating agent DMBA (400 nmol) was applied on the back skin of male and female DBA/2 mice. Testing for tumor promoting activity began 10 days after initiation. Tetradecanoyl phorbol acetate (TPA) (5 nmol, positive control), lyophilized latex (20, 60 and 200 microg per mouse) or acetone (vehicle control) were applied on mouse back skin twice a week for 20 weeks. In TPA-treated mice, papillomas were firstly noted during the 11th week, and by the 17th week all animals exhibited skin tumors. No tumors developed in mice treated with the solvent alone and in those exposed to latex. Findings from the present study therefore indicated that E. milii crude latex does not act as a tumor promoting agent on the mouse back skin assay.
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PMID:Absence of tumor promoting activity of Euphorbia milii latex on the mouse back skin. 1458 Nov 70

Activation of invariant NKT (iNKT) cells in the liver is generally regarded as the critical step for Con A-induced hepatitis, and the role of NK cell receptors for iNKT cell activation is still controversial. In this study we show that blockade of the NKG2A-mediated inhibitory signal with antagonistic anti-NKG2A/C/E mAb (20d5) aggravated Con A-induced hepatitis in wild-type, Fas ligand (FasL)-mutant gld, and IL-4-deficient mice even with NK cell and CD8 T cell depletion, but not in perforin-, IFN-gamma-, or IFN-gamma- and perforin-deficient mice. Consistently, 20d5 pretreatment augmented serum IFN-gamma levels and perforin-dependent cytotoxicity of liver mononuclear cells following Con A injection, but not their FasL/Fas-dependent cytotoxicity. However, blockade of NKG2A-mediated signals during the cytotoxicity effector phase did not augment cytotoxic activity. Activated iNKT cells promptly disappeared after Con A injection, whereas NK1(-) iNKT cells, which preferentially expressed CD94/NKG2A, predominantly remained in the liver. Pretreatment with 20d5 appeared to facilitate disappearance of iNKT cells, particularly NK1(-) iNKT cells. Moreover, Con A-induced and alpha-galactosylceramide-induced hepatic injury was very severe in CD94/NKG2A-deficient DBA/2J mice compared with CD94/NKG2A-intact DBA/2JJcl mice. Overall, these results indicated that a NKG2A-mediated signal negatively regulates iNKT cell activation and hepatic injury.
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PMID:NKG2A inhibits invariant NKT cell activation in hepatic injury. 1910 56

Immune-mediated adverse drug reactions (IADRs) represent a significant problem in clinical practice and drug development. Studies of the underlying mechanisms of IADRs have been hampered by the lack of animal models. Halothane causes severe allergic hepatitis with clinical features consistent with an IADR. Our ultimate goal is to develop a mouse model of halothane hepatitis. Evidence suggests that adaptive immune responses targeting liver protein adducts of the reactive metabolite (trifluoroacetyl (TFA)) play an important role in the pathogenesis. The present study demonstrated that the combination of an anti-CD40 antibody (Ab) and a Toll-like receptor (TLR) agonist served as a potent adjuvant in generating TFA-specific T cell responses in mice. Both CD4(+) and CD8(+) subsets of T cells were activated and the TFA-specific responses were detected not only in the spleen but also in the liver of mice immunized with mouse serum albumin adducts of TFA (TFA-MSA) plus the combined CD40/TLR agonist. Whereas all three TLR agonists examined were effective in eliciting TFA-specific immune responses in BALB/cByJ mice, only polyI:C was effective in DBA/1 mice and none of the TLR agonists could aid the generation of TFA-specific T cells in C57BL/6J mice. This result, combined with our previous finding that BALB/cByJ mice were the most susceptible to halothane-induced acute liver injury, provides the basis for employing this strain in future studies. Collectively, our data demonstrated the successful completion of a crucial first step in the development of a murine model of halothane hepatitis.
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PMID:Generation of T cell responses targeting the reactive metabolite of halothane in mice. 2015 33

To evaluate murine norovirus (MNV) infection in laboratory mice, we attempted to develop an enzyme-linked immunosorbent assay (ELISA) system and an indirect immunofluorescent antibody (IFA) assay for detecting the anti-MNV-S7 antibody in mice. MNV-S7, which was isolated in Japan, was used in both assays. The antigen for ELISA was prepared by ultracentrifugation of culture supernatants of RAW 264 cells infected with MNV-S7. Positive sera were obtained from 6-week-old, female C57BL/6JJcl mice inoculated orally with MNV-S7. IFA against infected RAW 264 cells was able to discriminate positive sera from negative sera. Indirect ELISA was performed using 96-well ELISA plates coated with formalin-treated MNV-S7 antigen. In this ELISA system, mouse sera obtained 2 weeks after infection or later showed significantly high OD values and were judged positive. An equal level of anti-MNV-S7 antibody response was observed in BALB/cAJcl, C57BL/6JJcl, DBA/2JJcl, and Jcl:ICR mice; whereas, C3H/HeJJcl mice demonstrated slightly lower antibody production 4 weeks after infection. We also used this ELISA system to evaluate 77 murine serum samples obtained from 15 conventional mouse rooms in research facilities in Japan and found that approximately half of the serum samples contained antibody to MNV-S7. We found that some serum samples were negative for antibodies to mouse hepatitis virus and Mycoplasma pulmonis but positive for antibody to MNV-S7. The results suggest that the MNV infection is more prevalent than other infections such as mouse hepatitis virus and Mycoplasma pulmonis in conventional mouse colonies in Japan, as is the case in other areas of the world.
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PMID:Indirect ELISA and indirect immunofluorescent antibody assay for detecting the antibody against murine norovirus S7 in mice. 2022 69


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