Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies with hepatocyte cultures have defined four hepatocyte mitogens which can transmit a complete mitogenic signal in cultures kept in completely defined conditions. These four mitogens are epidermal growth factor (EGF), acidic fibroblast growth factor (aFGF), hepatopoietin A/hepatocyte growth factor (HPTA/HGF) and hepatopoietin B (HPTB). In this study, we investigated the effect of aFGF, HGF and the mito-inhibitor transforming growth factor beta (TGF-beta) on cultured hepatocytes isolated from livers of rats treated with the xenobiotic hepatic tumor promoters phenobarbital (PB) and alpha-hexachlorocyclohexane (alpha-HCH). Male F344 rats were treated with each of these two xenobiotics to stimulate hepatic DNA synthesis and augmentative hepatomegaly. At different times on the regimens with tumor promoters, hepatocytes were isolated and placed in primary culture. DNA synthesis of hepatocytes in culture stimulated by these two growth factors and the suppression of DNA synthesis affected by TGF-beta were examined as a function of time of treatment in vivo with these two promoters. Following day 10, hepatocytes from both promoter regimens became unresponsive to these two growth factors for the rest of the duration of the treatment (day 90). TGF-beta suppressed DNA synthesis stimulated by growth factors but did not affect the high background DNA synthesis stimulated by xenobiotics themselves.
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PMID:Long-term treatment with hepatic tumor promoters inhibits mitogenic responses of hepatocytes to acidic fibroblast growth factor and hepatocyte growth factor. 171 12

We studied pathogenesis of hepatomegaly in Crow-Fukase syndrome. Hepatocytes were isolated from BALB/c mice and cultured with serum or ascites of three patients with Crow-Fukase syndrome. After 24 hours culture, total number of hepatocytes was counted. The levels of human hepatocyte growth factor (h-HGF) in the serum were also measured. In the hepatocyte culture study, the numbers of hepatocytes after 24 hours cultured in the serum of two patients were significantly larger than those of the control group. When the hepatocytes were cultured with patients' serum after corticosteroid therapy, the survival numbers were markedly reduced. The serum levels of h-HGF in our three patients were 0.62, 0.52, 0.53 ng/ml respectively. They were all slightly higher than normal values (< or = 0.39 ng/ml). Our study indicates that in the serum or ascites of patients with Crow-Fukase syndrome, there may be some humoral factors other than h-HGF, which promote proliferation of hepatocyte or protect hepatocyte.
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PMID:[A study on the pathogenesis of hepatomegaly in patients with Crow-Fukase syndrome]. 881 Aug 45

We reported a case of Crow-Fukase syndrome and examined the mechanism of hepatomegaly in Crow-Fukase syndrome. A 67-year-old woman was presented with polyneruopathy, hepatosplenomegaly, pericardial effusion and M proteinemia. On examination, all laboratory data and clinical symptoms were compatible with Crow-Fukase syndrome. The patient was treated with prednisolone and immunoadsorption plasmaphresis therapy. All the clinical manifestations including hepatomegaly gradually improved. In order to examine whether some factors that promote the prolifelation of hepatocyte may exist in the patient's serum, we cultured mouse hepatocyte in the presence of patient's or control serum together. Though the number of hepatocytes decreased after 2 days culture, the number of hepatocytes cultured with patient's serum in active disease stage remained significantly greater than of hepatocytes cultured with either control serum or patient's serum in healing stage. There were no abnormal pathological findings in biopsied liver. Liver suggesting that hepatomegaly was the results of normal hepatocytes proliferation. Taken together, these findings suggest there were some factors that may promote the proliferation of hepatocytes or may have protective effect of hepatocyte in patient's serum. Though the level of human hepatocyte growth factor (h-HGF) in patient's serum in active disease stage was slightly increased, hepatomegaly cannot be attributable solely to h-HGF. Organomegaly is one of the important symptoms of the Crow-Fukase syndrome, however, in so far as we are aware its mechanism is not examined. In this report it is suggested that several unknown factors other than h-HGF may contribute the hepatomegaly of the Crow-Fukase syndrome.
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PMID:[The detection of factors that may promote the hepatocyte proliferation in the serum of a patient with crow-fukase syndrome]. 885 11

The liver can precisely regulate its growth and mass. Surgical resection of hepatic lobes or hepatocyte loss caused by viral or chemical injury triggers hepatocyte replication while enlarged liver mass is corrected by apoptosis. Hepatocytes have a great replicative capacity and are capable of repopulating the liver. However, "stem-like" cells proliferate when hepatocyte replication is blocked or delayed. Detailed studies of the mechanisms that regulate liver growth have been done in animals subjected to partial hepatectomy or chemical injury. Substantial progress has been achieved using appropriate transgenic and knockout mouse models for this work. Gene expression in the regenerating liver can be divided into several phases, starting with expression of a large number of immediate early genes. Hepatocytes need to be primed before they can fully respond to the growth factors HGF (Hepatocyte Growth Factor), TGFalpha (Transforming Growth Factor Alpha), and EGF (Epidermal Growth Factor) in vitro. Priming requires the cytokines TNF and IL-6 in addition to other agents that prevent cytotoxicity. Reactive Oxygen Species and glutathione content can determine whether the TNF effect on hepatocytes is proliferative or apoptotic. At least four transcription factors, NFkappaB, STAT3 (which are strongly induced by TNF), AP-1 and C/EBPbeta play major roles in the initiation of liver regeneration. In addition, extensive remodeling of the hepatic extracellular matrix occurs shortly after partial hepatectomy. Progression through the cell cycle beyond the initiation phase requires growth factors. The expression of Cyclin D1 probably establishes the stage at which replication becomes growth factor-independent and autonomous. Knowledge about the mechanisms of liver regeneration can now be applied to correct clinical problems caused by deficient liver growth.
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PMID:Liver regeneration. 1072 91

It is well known that various kinds of hypolipidemic drugs induce marked changes in the livers of rats and mice. The initial hepatic responses in rodents are marked hepatomegaly, proliferation of peroxisomes in association with changes in peroxisome structure and enzyme composition. Furthermore, since many of hypolipidemic peroxisome proliferators induce hepatocellular carcinomas in both rats and mice, the relationship between peroxisome proliferation and hepatocarcinogenicity of these drugs has become extremely important. However, it has not yet been established whether there are any direct relationships among pharmacological action, peroxisome proliferation and carcinogenicity of these drugs. In order to clarify this task, we have studied the involvement of HGF in hepatocarcinogenesis caused by peroxisome proliferators. After male F-344 rats were orally given Wy-14,643, hepatocarcinomas and (pre) neoplastic nodules were observed in the livers. At that time, the content of HGF and the expression of HGF mRNA were significantly decreased in the liver tumors. These findings may indicate that decreases in hepatic HGF levels are specific events induced by peroxisome proliferators but not by genotoxic carcinogenesis, and that those changes play an important role in the promotion of neoplastic or preneoplastic cell growth induced by peroxisome proliferators. Decrease in HGF induced by peroxisome proliferators such as Wy-14,643 would inhibit the growth of normal hepatocytes and then lend an advantageous circumstance for the selective growth of neoplastic or preneoplastic cells, resulting in the development of growth of tumors.
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PMID:Hepatocarcinogenesis by peroxisome proliferators. 1501 50