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)

Patients with autoimmune hepatitis (AIH) usually require immunosuppressive therapy for many years, if not for a lifetime. Experimental immunotherapy such as T-cell vaccination aims at manipulating the immune system in such a way that autoimmunity is specifically regulated to enable long-lasting correction of the disease process. We aimed to test the feasibility of T-cell vaccination as well as conventional immunosuppression in the murine model of experimental autoimmune hepatitis (EAH). EAH was induced in 5- to 7-week-old BALB/c mice by immunization with syngeneic liver homogenate in complete Freund's adjuvant. For T-cell vaccination, splenocytes were removed from animals 14 days after induction of EAH and from control animals, and activated in vitro by mitogen stimulation with Concanavalin A (Con A). Activated T cells were irradiated and injected at 5 x 10(7) cells per animal as T-cell vaccine. Immunosuppression in control animals was performed with prednisolone with or without azathioprine. T-cell vaccination with T cells from EAH animals, but not with irrelevant T cells, was able to protect animals from EAH, reducing the average disease severity from 2.2 (+/-0.3) to 0.5 (+/-0.3) (P < .01). T-cell vaccination was also able to treat EAH, because application of the vaccine 2 weeks after induction of the disease significantly reduced disease activity at week 4 from 2.4 (+/-0.4) to 1.1 (+/-0.2) (P < .05). Both passive transfer of disease and the capacity to protect by T-cell vaccination was mediated by CD4 T cells. Specific cellular recognition of activated disease-inducing T cells could be detected in vaccinated animals. Immunosuppressive drugs could also suppress EAH. Thus, T-cell vaccination in EAH is feasible and effective. Stimulation of a regulatory T-cell network is the likely mechanism of action by which T-cell vaccination can suppress EAH.
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PMID:Suppression of murine experimental autoimmune hepatitis by T-cell vaccination or immunosuppression. 962 Mar 24

The aims of this study were to analyze the mortality directly attributable to chronic viral hepatitis in HIV-1 infected patients and to investigate the influence of hepatitis virus infections on the survival of this population. A cohort of 328 HIV-1 infected, antiretroviral-treated patients, followed up from 1989 to 1996, was investigated in the study. The median follow-up period of the cohort was 120 weeks. The median baseline CD4 + cell count of the cohort was 303 cells/mm3. Hepatitis C virus, hepatitis B virus and hepatitis D virus infections were present in 214 (65%), 16 (4.9%) and 9 (2.7%) patients, respectively. Sixty-seven (20.4%) subjects died but there was no information on the vital status of 36 patients (11%). The causes of mortality were AIDS in 49 (73%), liver failure in 3 (4.5%) and other causes in 15 (22.4%). The cohort was divided into two groups for survival analysis, the groups consisting of persons infected by a hepatitis virus and persons without hepatitis virus infection. There was no difference in survival between the two groups (p = 0.31, log-rank). It is concluded that mortality among HIV-1/hepatitis virus coinfected patients with moderate to severe immunosuppression is mostly due to AIDS, and that the survival of these subjects is not influenced by the presence of hepatitis virus infections, particularly hepatitis C virus.
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PMID:Influence of hepatitis C virus infection on the mortality of antiretroviral-treated patients with HIV disease. 966 97

Propagermanium is an organic germanium compound with immunopotentiating activity. We examined the hepatoprotective effect of propagermanium and its mechanism in an experimental animal model of acute liver injury induced with Corynebacterium parvum (C. parvum) and lipopolysaccharide (LPS) injection. Oral pretreatment with propagermanium decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in a dose-dependent manner. Significant attenuation of ALT and AST activity was obtained at a dose of 3 mg/kg. Administration of propagermanium also inhibited the infiltration of mononuclear cells into the liver of mice induced by C. parvum/LPS. Immunohistochemical examination revealed infiltration of the liver by CD4-, CD8-, CD11b- and Gr-1-positive cells. Propagermanium prevented CD4- and CD11b-positive cells from infiltrating the liver. In this animal model, blood cytokine levels increased rapidly after LPS injection, causing severe hepatitis. Notably, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) are important mediators of the progress of liver injury. We demonstrated that propagermanium reduced IFN-gamma production by 53% at a dose of 3 mg/kg and also significantly inhibited the production of interleukin-12 (IL-12). These results indicate that propagermanium inhibits cell infiltration in the liver and cytokine production, and improves massive liver injury in C. parvum/LPS mice.
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PMID:Hepatoprotective effect of propagermanium on Corynebacterium parvum and lipopolysaccharide-induced liver injury in mice. 971 10

The liver injury in the concanavalin A (Con A)-induced mouse hepatitis model has been well studied. However, there has been little study on the effects of Con A on extrahepatic organs. The aim of the present work was to determine the effects of Con A on the spleen, kidney and lung. A histopathological study showed that Con A (15 mg/kg, i.v.) administration affects not only the liver, but also all these extrahepatic organs. Messenger RNA expression was studied by the using polymerase chain reaction. Treatment with Con A induced interleukin-2 mRNA in the spleen, but only slightly induced it in the kidney. The mRNAs of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) were induced in all these organs. At 24 hr after Con A treatment, the expression of IFN-gamma mRNA, but not that of TNF-alpha mRNA, was inhibited by cyclosporine A (50 mg/kg, i.p.), suggesting that Con A induced these cytokine mRNAs through different mechanisms. In the kidney and lung, CD4+ and CD8+ T-cell infiltration was suggested by the Con A-induced CD4 and CD8 mRNAs. The present study showed the histopathological effects of Con A and Con A-induced cytokine mRNA expression on the spleen, kidney and lung.
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PMID:Expression of cytokine mRNA in extrahepatic organs in a mouse concanavalin A-hepatitis model. 971 69

Little is understood of the anatomical fate of activated T lymphocytes and the consequences they have on the tissues into which they migrate. Previous work has suggested that damaged lymphocytes migrate to the liver. This study compares class I versus class II major histocompatibility complex (MHC)-restricted ovalbumin-specific T cell antigen receptor (TCR) transgenic mice to demonstrate that after in vivo activation with antigen the emergence of CD4(-)CD8(-)B220(+) T cells occurs more frequently from a CD8(+) precursor than from CD4(+) T cells. Furthermore, this change in phenotype is conferred only by the high affinity native peptide antigen and not by lower affinity peptide variants. After activation of CD8(+) cells with only the high affinity peptide, there is also a dramatically increased number of liver lymphocytes with accompanying extensive hepatocyte damage and elevation of serum aspartate transaminase. This was not observed in mice bearing a class II MHC-restricted TCR. The findings show that CD4(-)CD8(-)B220(+) T cells preferentially derive from a CD8(+) precursor after a high intensity TCR signal. After activation, T cells can migrate to the liver and induce hepatocyte damage, and thereby serve as a model of autoimmune hepatitis.
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PMID:Liver damage preferentially results from CD8(+) T cells triggered by high affinity peptide antigens. 974 33

Increased susceptibility to tuberculosis occurs in the alcoholic. One explanation for the altered susceptibility is a change in T-lymphocyte modulation. To evaluate this, 24 male and 24 female Sprague-Dawley rats were treated with either a Lieber-type liquid ethanol diet (LED) or an isocaloric control (LCD). After 2 weeks, half the subjects were infected with BCG (10(8) colony-forming units) and sacrificed after 42 days. Splenic helper (CD4) and suppressor/cytoxic (CD8) cells were quantitated by flow cytometry. By three-way analysis of variance, splenic cellularity was significantly increased by infection (p < 0.0001) but suppressed by LED (p = 0.0002). There was a marginal sexual difference (p = 0.065) with females exhibiting a 35% lower response while on alcohol. Examining lymphocyte subsets, the most significant changes were observed after infection (BCG) and alcohol treatment (LED). CD4 levels were diminished by LED (p = 0.0002) but markedly increased by infection (p < 0.0001), producing a highly significant interaction that affected both absolute number (p < 0.0001) and relative percent present (p = 0.0078). CD8 was influenced only by infection (p < 0.0001). This resulted in a infection-related increase in the CD4/CD8 ratio which was lower with LED (p = 0.0032). Splenic T-lymphocytes, predominately CD4, are involved in the host response to BCG hepatitis and are adversely influenced by LED, which may contribute to increased susceptibility.
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PMID:Host response to mycobacterial infection in the alcoholic rat: male and female dimorphism. 974 51

The role of CD4+ T cells in altering the activity of cytotoxic T lymphocytes (CTL) during infection of the central nervous system (CNS) by the neuroptropic JHMV strain of mouse hepatitis virus was examined. Adoptive transfer of in vitro activated CTL into CD4-depleted and control recipients showed that CTL were not effective in reducing JHMV replication within the CNS. The distribution of CD4+ and CD8+ T cells within the CNS during JHMV infection showed that the CD4+ T cells remained in perivascular and subarachnoid spaces and few entered the parenchyma. By contrast approximately half of the CD8+ T cells entered the parenchyma. In CD4-depleted mice the trafficking of CD8+ T cells was not inhibited; however, the majority of the cells were found to be apoptotic. These data suggested that CD4+ T cells were not required for CTL induction but were required for the maintenance of CTL viability. The limited role of CD4+ T cells in CTL induction was confirmed by comparison of CTL activity from CD4-depleted and control mice.
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PMID:Apoptosis of JHMV-specific CTL in the CNS in the absence of CD4+ T cells. 978 10

The recent elucidation of the life cycle and dynamics of the human immunodeficiency virus (HIV) and technological advances in development of the HIV RNA PCR assay for sensitive detection of viral load have revolutionized the diagnosis, management, and treatment of HIV infection. Beginning with initial infection, there is unremitting, high-level viral replication that persists throughout the course of HIV infection. The measure of the amount of virus present in plasma, HIV viral load, is the single most important predictor of HIV progression, the best indicator of immune system decline, and the best guide for initiating and monitoring antiviral treatment. Further, HIV viral load has become the new yardstick against which other markers, including CD4 number, age, chemokine receptor mutations, cytotoxic T-cell responses, and neutralizing antibody titers are assessed. For individuals with haemophilia, additional 'markers' may have significant impact on the outcome of HIV disease. Chronic factor concentrate treatment has led to transfusion-associated hepatitis, co-infection with hepatitis C (HCV), and chronic liver disease. The latter may become accelerated with HIV progression and may lead to hepatotoxicity with antiviral drug therapy. Chronic factor concentrate treatment has also been associated with immunosuppression, including both B- and T-cell immune defects. In HIV(+) haemophilic men, this immune deficit has led to lower CD4 counts with HIV progression and poorer CD4 response to antiviral drugs than in gay men. The underlying haemophilic bleeding tendency may result in significant haemorrhage with HIV-associated immune thrombocytopenia and with protease inhibitor antiretroviral therapy. Although AIDS is the leading cause of death in this group, the reduction in the size of the haemophilia population over the next two centuries is estimated to be small, and survival should improve as better antiviral therapeutics are identified.
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PMID:Progression of HIV in haemophilia. 987 1

Propagermanium (3-oxygermylpropionic acid polymer) is an organic germanium compound that activates the immune system. In this study, we investigated the action of propagermanium on T-cell-mediated murine hepatic injury induced by concanavalin A (Con A). Oral administration of propagermanium inhibited the development of liver injury about 10 h after ConA injection. Histological analysis demonstrated that propagermanium attenuated the extent of liver damage compared with controls, reducing infiltration by leucocytes, especially CD11b-positive cells. Infiltration by CD4-positive cells was not affected. Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma are crucial for the development of hepatitis in this model. Propagermanium treatment induced significant inhibition of subsequent TNF-alpha production about 10 h after Con A injection, without affecting IFN-gamma, interleukin (IL)-10, IL-4 and IL-12 production. This effect on TNF-production coincided with the inhibition of aminotransferase activity late in the progression of Con A-induced liver injury. These facts suggest that this compound affects the macrophages (Mphi) function in the liver sinusoid. Therefore, Mphi were cultured with liver sinusoidal endothelial cells (SEC) and the effect of propagermanium on TNF-alpha production in the presence of IFN-gamma was determined. TNF-alpha production was reduced significantly in the coculture of Mphi and SEC when Mphi was treated with propagermanium. These results might explain the mechanisms by which propagermanium inhibits Con-A-induced liver injury. That is, propagermanium improves hepatitis through mechanisms including the reduced production of TNF-alpha, without modification of Th1- and Th2-cell function.
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PMID:Protection against concanavalin A-induced murine liver injury by the organic germanium compound, propagermanium. 987 94

A previously healthy 10-year-old Greek boy born to nonconsanguineous healthy parents developed progressive liver disease after acute infectious mononucleosis. EBV-induced autoimmune hepatitis was suspected and treatment was started with high-dose prednisolone, acyclovir and intravenous immunoglobulins. Despite therapy, his liver function continuously deteriorated and the child died 9 months later in profound immune deficiency from candida septicemia. Flow cytometric analysis of his lymphocytes revealed a major subpopulation of atypical cells (20.3%) which were CD3+, fitted into the lymphocyte gate but showed a very low level of CD4 expression, comparable to that of monocytes. After short-time cell culture, the cells became adherent and developed granules and dendrites. We conclude that these cells may represent strongly activated CD4+ T lymphocytes with downregulated CD4 expression or a subtype of dendritic cells.
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PMID:Atypical CD3+ CD4(low) cell population in a boy with fatal EBV-infection. 992 66


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