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)

Paraffin-embedded liver tissue from 60 biopsied or autopsied cases, including 20 cases each of acute mild hepatitis, chronic active hepatitis and active cirrhosis were studied with immunohistochemical double labelling technique by using polyclonal anti-Fas and anti-Fas ligand. The detection rates for Fas and Fas ligand were 76.7% (46/60) and 70.0% (42/60), respectively. Fas antigen was located in cytoplasm of hepatocytes. Fas ligand was expressed mainly in infiltrating lymphocytes in portal or periportal areas (34/42, 80.9%) and also in the cytoplasm of some hepatocytes (25/42, 59.5%). The distribution of Fas ligand-positive hepatocytes was similar to that of Fas-positive hepatocytes in liver tissue. The positive cells were scattered in the intralobular areas in acute mild hepatitis, but they were more commonly aggregated in periportal areas, especially near the edges of the piecemeal necrosis region or in infiltrating mononucleocytes in chronic active hepatitis and active cirrhosis, Double labelling studies showed that both Fas and Fas ligand might be expressed in the same or different hepatocytes of the same area. Our results suggest that Fas-Fas ligand system may play an important role in liver cell injury due to hepatitis B virus infection.
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PMID:[Expression of Fas and Fas ligand in liver tissue infected with hepatitis B virus]. 1043 77

Fifteen and ten years have passed since original anti-human Fas mAb CH-11 with associated apoptosis-inducing activity was prepared in 1984 and reported in 1989, respectively. Fas antigen (FS-7 cell-associated cell surface antigen) has been shown to be a cell surface receptor molecule (Fas) which can introduce apoptosis-inducing signals into Fas-bearing cells. Studies on lpr (lymphoproliferation) and gld (generalized lymphoproliferative disease) mice, which are loss-of-function mutant mice of Fas and Fas ligand (FasL), respectively, show that these mutations are responsible for the early onset of systemic autoimmune disease in MRL mice, suggesting that autoreactive immunocytes are eliminated by the function of Fas/FasL system ("physiological function" of Fas). Fas/FasL system, however, plays an important role in not only prevention but also aggravation of autoimmune disease. Fas/FasL was shown to be involved in the mechanisms responsible for tissue disruption in autoimmune diseases ("pathological function" of Fas). Studies on the in vivo administration of anti-mouse Fas mAbs, Jo2 and RK-8, emphasized pathological and physiological functions of Fas, respectively: Jo2 induces fulminant hepatitis and RK-8 ameliorates systemic autoimmune disease without the induction of fulminant hepatitis. The different in vivo effects of Jo2 and RK-8 coincide well with different target cell specificity of these mAbs in vitro. Similarly, I observed different target cell specificity on anti-human Fas mAbs. In this review, I propose new strategy of therapeutic use of anti-Fas mAb as specific suppressor for activated immune system on autoimmune disease and other diseases.
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PMID:Effects of anti-Fas antibodies on lymphocytes and other organs: preparation of original and new monoclonal antibodies and amelioration of systemic autoimmune disease. 1062 47

We used the terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling (TUNEL) method to detect apoptosis, and immunohistochemical staining for molecules related to apoptosis, a marker of cell proliferation, and surface markers of lymphocytes to examine 20 patients with autoimmune hepatitis (AIH). Confluent hepatic necrosis was frequently found, in which rosette formation of hepatocytes and ductular proliferation were common. TUNEL staining and staining for Lewis Y antigen, Bax protein, and Fas antigen were found in biliary epithelial cells in bile ducts and proliferating atypical bile ductules in regions of confluent necrosis with severe lymphocytic infiltration. TUNEL staining and staining for Lewis Y antigen and Bax protein were found in rosette-forming hepatocytes. Many hepatocytes in lobules without injury were stained for proliferating cell nuclear antigen (PCNA). bcl-2 oncoprotein was found in many lymphocytes surrounding proliferating atypical bile ductules and rosette-forming hepatocytes in regions of confluent necrosis, in which CD20 and OPD 4 were found. Apoptosis of both hepatocytes in rosette arrangement and biliary epithelial cells in bile ducts and proliferating atypical bile ductules may play a role in progression of AIH as well as confluent hepatic necrosis.
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PMID:Significant role of apoptosis in type-1 autoimmune hepatitis. 1072 2

To date, there have been no reports of the involvement of the Fas system in recurrent hepatitis C virus (HCV) infection after orthotopic liver transplantation (OLT). In 25 patients who underwent OLT for HCV-related liver cirrhosis, we evaluated the expression of the Fas antigen (FasAg) on hepatocytes, apoptic hepatocytes, and serum levels of soluble Fas (sFas). The level of HCV viremia and HCV genotype were determined by polymerase chain reaction. Serum sFas levels were determined by an enzyme immunoassay procedure. DNA fragmentation was determined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) technique on deparaffinized liver samples. FasAg expression was evaluated by an immunoperoxidase method. Sixteen patients had evidence of recurrent HCV disease. The number of hepatocytes expressing FasAg and the percentage of apoptotic hepatocytes was greater among patients who developed recurrent hepatitis than among those who did not (P <.01 and P <.0001, respectively). There was a correlation between hepatic expression of FasAg, intensity of lobular inflammation (P =.007), and TUNEL index (P <.001). The levels of sFas were greater among the patients with recurrent HCV hepatitis than those without recurrent hepatitis (P <.04). We conclude that (1) Fas expression is up-regulated in recurrent HCV after OLT and is related to the grading of liver disease; likewise, levels of sFas were greater in the patients with recurrent HCV hepatitis; and (2) the demonstration of hepatocytes with FasAg expression and the labeling of the nuclei by TUNEL assay suggest that hepatic apoptosis mediated by the Fas system may have a role in the pathogenesis of recurrent HCV hepatitis after OLT.
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PMID:Involvement of the fas system in hepatitis C virus recurrence after liver transplantation. 1098 54

The experimental data in recent years suggest apoptosis of liver cells plays a significant role in the pathogenesis of viral hepatitis. Firstly, the number of apoptotic hepatocytes in patients with hepatitis B or C is significantly higher than healthy objects. Secondly, the expression levels of Fas antigen in hepatocytes of patients with hepatitis B or C are closely correlated with inflammation activity. Thirdly, massive apoptosis of hepatocyte will result in fulminant hepatitis, while inhibition of apoptosis can prevent inflammation in experimental model of liver injury. And finally, the occurrence of hepatitis induced by CTL in transgenic mice is a process from hepatocyte apoptosis to liver necroinflammation. This paper will examine our current understanding of the possible relationship between hepatocellular apoptosis and the pathogenetic mechanism of hepatitis B and C.
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PMID:A new hypothesis of pathogenetic mechanism of viral hepatitis B and C. 1135 71

The pathogenesis of the fulminant hepatitis B is poorly understood and both viral factors and the hosts immune response play a role. Previous studies in liver tissues of patients with chronic hepatitis B showed overexpression of Fas antigen and this was correlated with the activity of the hepatitis. The present study was done to determine the role of Fas in fulminant hepatitis B and the virological characteristics of hepatitis B infection. We studied three patients with fulminant hepatitis B. HBV-DNA was detected by dot-blot hybridization and polymerase chain reaction. The S and C gene were sequenced. Levels of serum soluble Fas antigen were detected by enzymoimmunoassays procedure. Apoptosis was determined by the TUNEL technique. Fas antigen expression was evaluated by a immunoperoxidase method. Ten healthy subjects acted as controls. The three patients showed a high expression of Fas antigen particularly among infiltrating lymphocytes; in these areas we also found many cells with in situ DNA nick labelling signals in the nuclei of most viable hepatocytes. Serum levels of soluble Fas antigen were higher in patients with fulminant hepatitis B than in controls. No specific genome mutations of hepatitis B virus were found. These data suggest that the Fas system involved in the liver injury of patients with fulminant hepatitis B.
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PMID:Apoptosis mediated by the Fas system in the fulminant hepatitis by hepatitis B virus. 1187 92

Fas antigen (Fas) is a cell surface receptor molecule introducing apoptosis-inducing signals into Fas-bearing cells by stimulation with Fas ligand or agonistic anti-Fas monoclonal antibodies. Fas system has been implicated in the regulation of homeostasis of peripheral T and B lymphocytes including elimination of autoreactive cells, and in the exclusion of tumor and virus-infected cells. Fas system, however, also plays a role in the mechanisms responsible for tissue disruption in tissue-specific autoimmune disease and fulminant hepatitis. In this review, I describe how we prepared the original anti-human Fas monoclonal antibody with associated cell-killing activity, and I propose here a strategy of therapeutic use of a novel anti-Fas monoclonal antibody for autoimmune and other diseases.
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PMID:Death receptor Fas and autoimmune disease: from the original generation to therapeutic application of agonistic anti-Fas monoclonal antibody. 1222 May 52

Recently, liver natural killer T (NKT) cells, which are specifically stimulated by alpha-galactosylceramide (alpha-GalCer), were found to play a critical role in intrahepatic immunity to several infections and certain hepatic disorders. However, the role of psychophysical stress on NKT cell-dependent liver injury induced by alpha-GalCer still remains to be elucidated. In this study, we employed inescapable electric foot shock as the mode of psychophysical stress and evaluated its effect on alpha-GalCer-induced hepatitis. Pre-exposure of 12 hours of foot shock stress before alpha-GalCer administration significantly enhanced alpha-GalCer-triggered increase in serum alanine aminotransferase levels, followed by increases in both liver caspase-3 activity and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive hepatocytes, thus indicating that the liver NKT cell-dependent apoptotic response was exacerbated by stress. Foot shock stress also significantly increased both the number of liver NKT cells and Fas expression levels on hepatocytes. Pretreatment with RU-486, a glucocorticoid (GC) receptor antagonist, completely reversed such stress-induced enhancement of the alpha-GalCer-triggered serum alanine aminotransferase and hepatocyte Fas antigen responses. In contrast, such a reversal effect was not found in the mice pretreated with naloxone, a micro-opioid receptor antagonist, which thus suggests that an elevation of endogenous GCs, but not beta-endorphin, as responsible for such stress-induced aggravation in mouse hepatitis models. In conclusion, foot shock stress-induced elevation of endogenous GCs exacerbates alpha-GalCer-initiated hepatic apoptosis through the expansion of liver NKT cells and the up-regulation of hepatocyte Fas antigen.
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PMID:Electric foot shock stress-induced exacerbation of alpha-galactosylceramide-triggered apoptosis in mouse liver. 1505 17

Concanavalin A (Con A)-induced hepatitis is a T-cell-mediated murine experimental model of autoimmune hepatitis. Mice lacking Valpha14 NKT cells were found to be less sensitive to this hepatitis and the MRL/Mp-Fas(lpr/lpr) (MRL/lpr; i.e. Fas deficient) mice were also less sensitive. We report herein that MRL/Mp-Fas(lpr/lpr)-Sap(rpl/-) (MRL/lpr/rpl) mice lack Valpha14 NKT cells and are deficient in the Fas antigen but sensitive to Con A-induced hepatitis. The signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is an adaptor molecule containing a Src homology 2 (SH2) domain. We previously reported new mutant mice found among MRL/lpr mice and revealed that SAP deficiency led to the regression of autoimmune phenotypes in mutant MRL/lpr/rpl mice. It was also revealed that CD4(+) and CD8(+) T cells were effector cells and that blockade of 2B4, one of the SLAM family receptors, inhibited the induction of hepatitis in MRL/lpr/rpl mice. These data suggest that signals mediated by molecules other than SAP from 2B4 in T cells played important roles in the induction of hepatitis in MRL/lpr/rpl mice.
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PMID:Role of 2B4-mediated signals in the pathogenesis of a murine hepatitis model independent of Fas and Valpha14 NKT cells. 1880 Sep 87


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