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)

Hepatic regeneration in partially hepatectomized, eviscerated rats, and survival in mice infected with lethal doses of murine hepatitis virus, are both strikingly promoted by combined administration of insulin and glucagon. These two hormones, although potent promotors, fail as initiators of hepatocyte proliferation in animals with intact liver, which suggests a requirement for additional factors, probably derived from non-portal-splanchnic organs. We now find that continous intraperitoneal infusion of epidermal growth factor (EGF) initiates DNA synthesis, as determined by incorporation of [3H] thymidine, in livers of adult rats in vivo. The rise in DNA labelling, which is small with EGF alone, is augmented by addition to the infusion of either glucagon or insulin. This is in agreement with reports on adult hepatocytes in culture. Whether EGF has a physiological role in regulating liver growth under normal conditions in vivo remains to be determined.
 ...
PMID:Hormonal factors concerned with liver regeneration. 30 14

The present study was undertaken to evaluate the ability of human hepatocytes to respond in culture to various mitotic agents including epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), or serum from patients with fulminant hepatitis. Human hepatocytes were maintained in culture on collagen-coated plates in a chemically and hormonally defined serum-free medium at low cell density. Twelve hours after plating, cultures were treated with increasing amounts of EGF (1-100 ng/mL), TGF-alpha (1-100 ng/mL), or human serum (1%-10%) for 0-96 hours. Proliferative response was assessed by determining against time the rate of DNA synthesis by [3H]thymidine incorporation in DNA, the labeling index, the expression of cyclin A, the amount of DNA, and the number of cells. The rate of DNA synthesis reached a maximum after 48 hours of treatment with 20 ng/mL EGF, 40 ng/mL TGF-alpha, or 5%-10% of human serum (fulminant hepatitis); the average increase with respect to untreated cells was 4.35 times with EGF, 5.4 times with TGF-alpha, and 4-6 times with serum from patients with fulminant hepatitis. The maximum expression of cyclin A coincided with the maximum of DNA synthesis. After 72 hours of treatment with EGF or human serum (fulminant hepatitis), the amount of DNA increased by 75%-100% (P less than 0.001) and the number of cells by 50% (P less than 0.001). These results show that adult human hepatocytes respond to mitogens, as expected from previous studies on animal hepatocytes, and provide experimental basis for future investigations in the field of human liver regeneration.
 ...
PMID:Mitotic responsiveness of cultured adult human hepatocytes to epidermal growth factor, transforming growth factor alpha, and human serum. 153 70

The rapid regenerative response of the rat liver to partial hepatectomy is associated with a decline in liver epidermal growth factor receptor numbers which implies that ligand epidermal growth factor receptor interactions maybe important in initiating and/or modulating this process. The proliferative process in toxic hepatitis (where in contrast with partial hepatectomy the majority of hepatocytes have been exposed to damaging influences) has been less widely investigated. We studied the DNA synthetic response of rat livers to toxic injury induced by a 350 or 800 mg/kg ip injection of galactosamine and that caused by 70% hepatectomy, comparing the changes in epidermal growth factor receptor status. Both resulted in down regulation of epidermal growth factor receptors, suggesting similar ligand epidermal growth factor receptor binding occurs during the proliferative response after galactosamine administration and after partial hepatectomy. In vitro studies on isolated hepatocytes showed that epidermal growth factor receptor down regulation was not a direct effect of galactosamine on hepatocyte membranes.
 ...
PMID:Galactosamine induced hepatitis induces a reduction in hepatocyte epidermal growth factor receptors. 164 37

In certain etiological groups of patients with fulminant hepatic failure, poor survival may be due to lack of liver regeneration. In vitro experiments have shown that fulminant hepatic failure serum is cytotoxic to rabbit hepatocytes and inhibits DNA synthesis on short-term incubation with isolated regenerating rat hepatocytes. When fulminant hepatic failure serum is injected into partially hepatectomized rats at the time of maximal DNA synthesis, [3H]thymidine incorporation into hepatic DNA is reduced significantly. The effect is greater with sera obtained from patients with fulminant hepatic failure due to non-A, non-B hepatitis or an adverse drug reaction and is associated with a less than 10,000-dalton fraction. No stimulation of DNA synthesis is observed with injection of the greater than 10,000-dalton serum fraction into normal rats. In preliminary experiments, no increase in epidermal growth factor production has been found in liver failure. Overall, the substances present in fulminant hepatic failure serum appear to be inhibitory rather than stimulatory for liver cell regeneration.
 ...
PMID:Inhibitors of hepatic DNA synthesis in fulminant hepatic failure. 203 22

Effects of various cytokines on the proliferation of mouse hepatocytes were investigated. Human recombinant IL-6 not only enhanced the proliferation of mouse hepatocytes in the presence of epidermal growth factor, but also without epidermal growth factor. However, other human or mouse cytokines such as recombinant IL-1, IL-2, IL-3, IL-4, IFN-beta and IFN-gamma, which are known to regulate immune responses and/or hematopoiesis, had no effect on the proliferation of hepatocytes. These results suggest that IL-6 plays a crucial role in regulating the regeneration of hepatocytes after hepatitis or partial hepatectomy.
 ...
PMID:Effect of human recombinant interleukin-6 on the proliferation of mouse hepatocytes in the primary culture. 218 3

The effect of sera from 8 patients with fulminant hepatitis, including 2 survival cases, on DNA and protein synthesis in primary cultured rat hepatocytes was studied. The serum from patients at an early stage or within 10 days after onset tended to intensify DNA synthesis in isolated hepatocytes, whereas the serum from patients with a history of over 50 days distinctly inhibited synthesis. When the serum was fractionated by gel filtration or free-flow electrophoresis, only the albumin fraction inhibited DNA synthesis in cultured hepatocytes. The suppressive effect of the albumin fraction was demonstrated even in patients suffering for only a short period of time. The inhibitory activity against DNA and protein synthesis in cultured hepatocytes was demonstrated in a substance extracted with a chloroform and methanol mixture from the albumin fraction of patients with fulminant hepatitis. The extract from the patients' sera also inhibited acceleration of DNA synthesis by epidermal growth factor (EGF) in the same cells.
 ...
PMID:Inhibitory activity of the serum from patients with fulminant hepatitis against liver regeneration. 373 55

We carried out the following three experiments to clarify the mechanism of hepatocarcinogenesis in Long-Evans Cinnamon (LEC) rats. (1) Sensitivity to diethylnitrosamine (DEN): LEC rats (8 and 25 weeks old) without and with hepatitis and age-matched F344 rats were administered an intraperitoneal injection of a low dose of DEN. Eight weeks after the injection, the numbers of glutathione-S-transferase placental-form (GST-P)-positive foci in the 33-week-old LEC rat liver were significantly higher than those in the livers of the other three groups of rats. (2) Potential for unscheduled DNA synthesis (UDS): Isolated hepatocytes of 25-week-old LEC rats with chronic hepatitis showed about one-third the level of UDS induced by UV irradiation, as compared to that of age-matched F344 rats, while no significant difference was found between the UDS of isolated hepatocytes of 8-week-old LEC rats and age-matched F344 rats. (3) Potential for proliferation: Isolated hepatocytes from 8-week-old LEC rats responded well to epidermal growth factor (EGF) in culture, to almost the same degree as F344 rat hepatocytes, while a remarkable decrease in the responsiveness of hepatocytes isolated from 25-week-old LEC rats to EGF was found. These results suggested that LEC rat hepatocellular carcinoma could be naturally initiated after the onset of hepatitis by carcinogens contaminating food and the environment, probably due to the reduction of DNA repair activity, after which initiated hepatocytes selectively proliferate in response to growth stimuli endogenously produced as a result of continuous loss of hepatocytes (chronic hepatitis), because of a decrease in growth activity of non-initiated hepatocytes.
 ...
PMID:High sensitivity of LEC rats with chronic hepatitis to hepatocarcinogenesis: decreases in unscheduled and replicative DNA synthesis of the hepatocytes. 840 64

In this study, the stimulatory effect of bile salts (BS) was evaluated both in vitro, using hepatocyte primary cultures, and in vivo, in normal and 40% partially hepatectomized rats previously fed on BS-enriched diets for 4 weeks. In vitro results show that conjugated cholate (CA) and chenodeoxycholate (CDCA) augmented proliferative activity in rat hepatocytes cultured in absence of mitogens, whereas conjugated deoxycholate (DCA), and ursodeoxycholate (UDCA) did not have any significant effect. None of these BSs increased significantly the replicative response induced by submaximal concentrations of epidermal growth factor (EGF). In vivo, at the end of dietary treatment all animals fed on CA or DCA but not those fed on either CDCA, or UDCA, or tauroursodeoxycholate (TUDCA) developed cholestatic hepatitis and a burst of damage-induced hepatocyte proliferation. After 40% partial hepatectomy (PH), CA- and DCA-treated groups underwent a deterioration of cholestatic hepatitis. On the other hand, in CDCA-, and UDCA-, and TUDCA-treated groups liver histology, serum glutamic pyruvic transaminase (SGPT) and cholestasis indices did not change significantly compared with controls. As far as the proliferative activity, a significant increase was observed not only in CA and DCA but also in UDCA- and TUDCA-fed groups compared with controls, whereas a slight decrease was observed in CDCA-treated animals. In conclusion, our data indicate that conjugated BSs had only a modest stimulatory effect on hepatocyte proliferation in vitro. However, in vivo, in PH rats, UDCA or TUDCA treatment determined a further increase of hepatocellular proliferation not attributable to hepatotoxic effects. Our result suggest that modifications of bile acid pool could modulate hepatocellular proliferation.
 ...
PMID:Modulation of rat hepatocyte proliferation by bile salts: in vitro and in vivo studies. 862 Nov 49

Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a member of the EGF family and is highly expressed in hepatoma tissues but not in normal liver. However, it is unknown when HB-EGF is induced during hepatocarcinogenesis and what are the mechanisms underlying its high expression in hepatoma. To address this issue, the expression of HB-EGF was investigated during hepatocarcinogenesis in LEC (Long-Evans with a cinnamon-like coat color) rats, which spontaneously develop hepatitis and hepatoma. LEA (Long-Evans with an agouti coat color) rats were used as controls. Furthermore, the induction of HB-EGF mRNA by various agents was investigated in a rat hepatoma cell line and hepatocytes in primary culture. Expression of HB-EGF mRNA in the liver was very low at the stage of acute and chronic hepatitis and markedly increased at the stage of hepatoma in LEC rats. Non-involved tissues adjacent to hepatoma showed low expression of HB-EGF mRNA. Immunochemical studies revealed positive staining in hepatoma tissues. Induction of HB-EGF mRNA by several growth factors was observed in a hepatoma cell line but not in normal hepatocytes. Our results suggest that HB-EGF is associated with the early progression steps of hepatoma.
 ...
PMID:High expression of heparin-binding EGF-like growth factor in rat hepatocarcinogenesis. 890 Apr 31

Picroliv, an iridoid glycoside derived from the plant Picrorhiza kurroa, is used traditionally to treat fever, asthma, hepatitis, and other inflammatory conditions. However, the exact mechanism of its therapeutic action is still unknown. Because nuclear factor-kappaB (NF-kappaB) activation plays a major role in inflammation and carcinogenesis, we postulated that picroliv must interfere with this pathway by inhibiting the activation of NF-kappaB-mediated signal cascade. Electrophoretic mobility shift assay showed that pretreatment with picroliv abrogated tumor necrosis factor (TNF)-induced activation of NF-kappaB. The glycoside also inhibited NF-kappaB activated by carcinogenic and inflammatory agents, such as cigarette smoke condensate, phorbol 12-myristate 13-acetate, okadaic acid, hydrogen peroxide, lipopolysaccharide, and epidermal growth factor. When examined for the mechanism of action, we found that picroliv inhibited activation of IkappaBalpha kinase, leading to inhibition of phosphorylation and degradation of IkappaBalpha. It also inhibited phosphorylation and nuclear translocation of p65. Further studies revealed that picroliv directly inhibits the binding of p65 to DNA, which was reversed by the treatment with reducing agents, suggesting a role for a cysteine residue in interaction with picroliv. Mutation of Cys(38) in p65 to serine abolished this effect of picroliv. NF-kappaB inhibition by picroliv leads to suppression of NF-kappaB-regulated proteins, including those linked with cell survival (inhibitor of apoptosis protein 1, Bcl-2, Bcl-xL, survivin, and TNF receptor-associated factor 2), proliferation (cyclin D1 and cyclooxygenase-2), angiogenesis (vascular endothelial growth factor), and invasion (intercellular adhesion molecule-1 and matrix metalloproteinase-9). Suppression of these proteins enhanced apoptosis induced by TNF. Overall, our results show that picroliv inhibits the NF-kappaB activation pathway, which may explain its anti-inflammatory and anticarcinogenic effects.
 ...
PMID:Modification of cysteine residue in p65 subunit of nuclear factor-kappaB (NF-kappaB) by picroliv suppresses NF-kappaB-regulated gene products and potentiates apoptosis. 3018 11


1 2 Next >>