Expression and localization of basic fibroblast growth factor (bFGF) in the repair process of rat liver injury.

BACKGROUND/AIMS: To clarify the expression and localization of basic fibroblast growth factor in the repair process of liver injury, acute liver injury was induced by administration of carbon tetrachloride, D-glactosamine hydrochloride, or dimethylnitrosamine to rats. METHODS: We measured basic fibroblast growth factor protein in the liver tissue by radioimmunoassay, evaluated the expression of basic fibroblast growth factor mRNA by the reverse transcriptase polymerase chain reaction, and identified basic fibroblast growth factor-positive cells by immunostaining. RESULTS: In the carbon tetrachloride injured liver, the basic fibroblast growth factor protein contents began to increase 2 days after administration when liver injury was most marked, and reached a peak after 4 days, decreasing thereafter. In the carbon tetrachloride-injured liver, basic fibroblast growth factor mRNA expression was observed from 12 h after administration, prior to an increase in the protein content. In the D-galactosamine hydrochloride-injured liver, basic fibroblast growth factor protein also increased. On the other hand, in the dimethylnitrosamine-injured liver, the basic fibroblast growth factor protein content decreased 2 days after administration when liver injury was marked, but increased after 7 days. In the regenerating liver after partial hepatectomy, the basic fibroblast growth factor protein content did not increase. Among cell fractions, the Ito cell fraction obtained from the carbon tetrachloride-injured liver after 4 days showed expression of basic fibroblast growth factor mRNA. In cells cultured for 24 h, this fraction was immunopositive for basic fibroblast growth factor. Ito cells in the liver tissue markedly increased in the carbon tetrachloride-injured liver and increased after 7 days in the dimethylnitrosamine-injured liver. CONCLUSIONS: This study confirmed basic fibroblast growth factor production in the liver tissue in the repair process of liver injury. Our results suggest that basic fibroblast growth factor is primarily produced in Ito cells, acts on sinusoidal wall cells including Ito cells by the autocrine and paracrine mechanisms, and promotes extracellular matrix production and vascularization, involving the repair process of liver injury.

Tentative diet for liver failure containing well-polished rice.

A liver-failure diet (low in protein) that contained rice polished to 50% to reduce the protein content of the diet was given to patients with uncompensated liver cirrhosis and compared with a standard liver-failure diet containing conventionally processed rice. The amount of boiled rice served in each meal could be increased by using well-polished rice and the use of supplementary sources of energy (powdered starch syrup, jelly, cookies, and candy sugar) was unnecessary. In the liver-failure diet containing well-polished rice, the methionine contents could be reduced and the Fischer ratio could be increased. The ingestion rate of the diet with well-polished rice was 80% and the diet was rated favorably in a questionnaire on palatability. Decreases in blood ammonia concentrations were observed in three patients given the liver-failure diet with well-polished rice for 2 wk by the crossover method.

Effects of an infusion of branched-chain amino acids on neurophysiological and psychometric testings in cirrhotic patients with mild hepatic encephalopathy.

Psychotropic action of a branched-chain-enriched amino acid solution (Aminoleban) was quantitatively and visually examined in six cirrhotic patients with mild hepatic encephalopathy (grades I and II) using electrophysiological and psychometric methods. Neurophysiological effects of the amino acid solution were observed by comparing topographic spectrum analyses of electroencephalography (EEG) before and immediately after an intravenous 3 h infusion of the solution. The delta wave in the frontal region diminished from 61 +/- 13 to 12 +/- 4% (P < 0.01) and the alpha wave in the occipital region increased from 11 +/- 3 to 51 +/- 11% (P < 0.01). Latencies of the P3 wave in visual evoked potentials, which were topographically recorded in the occipital region, shortened from 220 +/- 32 to 148 +/- 19 ms (P < 0.01). Latencies of the P300 wave in event-related potentials, which were topographically recorded in the centro-temporal region, shortened from 493 +/- 81 to 360 +/- 93 ms (P < 0.05). Topographic reaction pattern of P300 was irregular toward the occipital or parietal region in cirrhotic patients. The EEG frequency power spectrum, illustrated by the colour density spectral array of computer-aided polysomnography analysis, clearly showed a gradual increase of the alpha wave spectrum and a gradual decrease of the delta wave spectrum after initiation of the infusion. These immediate neurophysiological changes were confirmed by improvement of quantitative psychometric tests including number connection test, reaction time to sound, and digit symbol and block design tests of Wechsler Adult Intelligence Scale.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduction of increased signal intensity in the basal ganglia on T1-weighted MR images during treatment of hepatic encephalopathy.

A 61-year-old man with liver cirrhosis showed a symmetrical increase in the signal intensity of the basal ganglia on T1-weighted magnetic resonance (MR) images, which was diminished after 3 months of treatment for hepatic encephalopathy. He recovered from encephalopathy with treatment, and liver dysfunction (hyperammonemia and abnormal blood coagulation) as well as the results of quantitative psychometric tests showed a marked improvement. The cause of these high signal intensity changes on T1-weighted images and the reason for their partial reversibility are not known, but hyperammonemia due to portal-systemic shunting might be closely related to these clinical observations.

Clinical significance of serum hepatocyte growth factor levels in liver diseases.

Serum levels of human hepatocyte growth factor (hHGF) in patients with various liver diseases were determined using an ELISA kit to explore its clinical significance. Significantly high levels of serum hHGF were found in patients with acute hepatitis, fulminant hepatitis, liver cirrhosis, and hepatocellular carcinoma. Increased levels of hHGF were observed during severe liver injury in patients who died of fulminant hepatitis. However, the levels returned to normal during the repair process of liver injury in the surviving cases. In patients with liver cirrhosis, serum hHGF levels were negatively correlated with serum albumin (Alb) levels. These results indicate that serum hHGF levels are not useful for detecting repair processes of the injured liver, but serve as an index of the severity of liver dysfunction in various liver diseases.

Induction of allogeneic tumour- and lymphokine-activated lymphocytes against hepatocellular carcinoma.

For clinical application of adoptive immunotherapy against hepatocellular carcinoma (HCC), it is not easy to prepare tumour specific effector cells such as cytotoxic T lymphocytes (CTL). To induce potent and broad-spectrum effectors, allogeneic cultured hepatoma cell lines (JHH-4 and HuH-6) were used as stimulators of peripheral blood lymphocytes (PBL) instead of autologous HCC cells. Allogeneic tumour- and lymphokine-activated killer cells (ATLAK) were generated by a mixed culture of lymphocytes and allogeneic cultured tumour cells with recombinant interleukin-2 (rIL-2). The tumour-killing activity of ATLAK induced by HuH-6 was confirmed against HuH-6 and other different HCC cell lines (JHH-2, HuH-7 and PLC). These activated lymphocytes were significantly more potent than lymphokine-activated killer cells (LAK) in [51Cr]-releasing assay. The JHH-4 stimulated ATLAK was reactive not only with JHH-4 but also with JHH-2. The lysis of allogeneic targets could be partially inhibited by anti-CD8 and anti-CD3 but not by anti-CD4. Anti-tumour cytotoxicity in these cultures might be mediated by CD3+CD56- and CD3+CD56+ effectors. These results imply that adoptive immunotherapy for HCC with ATLAK may be more feasible than that with LAK.