[A case of double cancer, cholangiocellular and hepatocellular carcinoma associated with autoimmune hepatitis].
Explore the source record for details and available documents.
Autoimmune Diseases↗
Biomedical subjects
T Okanoue
Publications and source records attributed to T Okanoue.
Monokine production by peripheral whole blood in chronic hepatitis C patients treated with interferon.
Using our scoring system, we studied the production of monokines (interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6) by lipopolysaccharide-stimulated peripheral whole blood in 34 patients with chronic hepatitis C during the interferon-alpha/beta therapy. It decreased in 25.7% (9/35 group A), fluctuated in 60.0% (21/35, group B), and increased in 14.3% (5/35, group C). The patients in group A were younger than those in group B (P < 0.05). The histological grade of injury was milder in group A than in group B or C. The rate of sustained response was 66.7% (6/9) in group A, 19.0% (4/21) in group B, and 40.0% (2/5) in group C(P = 0.0184, group A versus group B). In summary, monokine production by peripheral whole blood varied during interferon therapy for chronic hepatitis C patients. No significant change was noted in 60% of the patients. However, patients with decreased monokine production were younger, with a mild histological grade, and likely to respond to the interferon therapy.
Adult↗
Identification of apoptotic hepatocytes in situ in rat liver after lead nitrate administration.
Apoptosis plays a major role in the regression of mitogen (lead nitrate)-induced hepatic hyperplasia. We compared the in situ end-labeling (ISEL) technique with the conventional detection of apoptotic bodies in this process. In hematoxylin and eosin (H&E) sections, apoptosis is usually recognizable by the presence of apoptotic bodies (apoptosis phase 2). Although the early phase of apoptosis (apoptosis phase 1) can be detected as a prekaryorrhectic appearance in H&E sections, it is difficult to detect and is easily overlooked. On the other hand, ISEL presents intense staining mainly in phase 1 and weak or negative staining in phase 2. Thus, simultaneous investigation by these two methods in two serial sections is the most reliable way to calculate the incidence of apoptosis and gives us precise information on the stages of apoptosis in situ. Since the colorized signals of ISEL are much easier to detect than apoptotic bodies in H&E sections, ISEL is particularly useful for liver tissues, where the incidence of apoptosis is low.
Animals↗
Augmented endogenous nitric oxide production in partial portal vein-ligated rats.
Explore the source record for details and available documents.
Animals↗
Augmented endogenous nitric oxide production in partial portal vein-ligated rats.
1. Endothelium-derived nitric oxide (NO) is a potent vasodilator. Because the body oxidizes it to nitrate ions, NO3-, measurement of the serum concentration and the urinary excretion of NO3- may be an index for endogenous NO. We investigated the role of NO on hyperdynamic circulation in cirrhotic and partial portal vein-ligated rats by measuring NO3. 2. Liver cirrhosis was induced by administration of thioacetamide. Systemic and splanchnic haemodynamics and splenic-systemic shunting were determined by tracer microspheres. The concentration of NO3- was measured by using high-performance liquid chromatography with an anioncolumn. 3. We found that systemic and splanchnic hyperdynamic circulation existed to almost the same extent in cirrhotic and in portal vein-ligated rats as compared to the controls and shamoperated rats, respectively. Splenic-systemic shunting was markedly greater in portal vein-ligated rats than in cirrhotic rats. 4. Serum NO3- levels and urinary excretion of NO3- in cirrhotic rats tended to increase as compared to the controls. On the other hand, the levels in portal vein-ligated rats were significantly increased as compared to those of the shamoperated rats, and were significantly and negatively correlated to the splanchnic arterial resistance and total vascular resistance. The amount of urinary excretion of NO3- significantly correlated to splenic-systemic shunting (r = 0.61, P < 0.05) only in portal vein-ligated rats. 5. We suggest that these high levels of NO3- in portal vein-ligated rats relate to the extensive formation of porto-collateral vasculature or acute changes in systemic and splanchnic haemodynamics due to portal vein-ligation.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Role of sinusoidal endothelial cells in liver disease.
We characterized the structural changes of sinusoidal endothelial cells in chronic ethanol-fed rats and rats with cirrhosis induced by thioacetamide. The phenotypic changes of sinusoidal endothelial cells in fibrotic rats induced by thioacetamide and the reversibility of these changes were also investigated under transmission and scanning electron microscopy, regular microscopy and by immunohistochemistry with laminin and von Willebrand factor antibodies. The diameter and porosity of sinusoidal endothelial fenestrations were increased in chronic ethanol-fed rats without liver fibrosis, however, they decreased within 4 weeks of the cessation of thioacetamide treatment. A basement membrane-like structure in Disse's space was noted 6 weeks after thioacetamide treatment. Laminin was detected in Disse's space after 4 weeks and von Willebrand factor was detected in the cytoplasm as granular fluorescence after 6 weeks of thioacetamide treatment. Reversibility of the phenotypic changes of the sinusoidal endothelial cells was demonstrated in fibrotic liver of rats that received thioacetamide for 6 weeks after long-term discontinuation of thioacetamide administration. These results indicate that the structural and immunohistochemical characteristics of sinusoidal endothelial cells change in chronic ethanol-fed rats and fibrotic rats and these changes are reversible.
Alcoholism↗
Serum autoantibody against interleukin-1 alpha is unrelated to the etiology or activity of liver disease but can be raised by interferon treatment.
OBJECTIVE: To clarify the clinical significance of serum levels of interleukin-1 alpha autoantibody in liver disease and their change during interferon therapy for chronic hepatitis. METHODS: By radioimmunoassay, we studied the incidence of serum interleukin-1 alpha autoantibody in 838 healthy controls and 180 patients with liver disease and monitored the change in antibody titer during the interferon therapy for chronic hepatitis. RESULTS: We detected the interleukin-1 alpha autoantibody in 12.6% (106/838) of healthy controls. In patients with liver disease, we found the antibody in 15.6% (5/32) in patients with acute hepatitis, 16.3% (13/80) in patients with chronic hepatitis, 18.8% (9/48) in patients with liver cirrhosis, and 15% (3/20) in patients with autoimmune liver disease. The incidence was not related to either etiology or inflammatory activity of liver disease. Two of three chronic hepatitis patients with initially high serum levels of the antibody (> 2000 ng/ml) showed transient increase in antibody titers during interferon therapy. CONCLUSION: The serum level of interleukin-1 alpha autoantibody was unrelated to the etiology or activity of liver disease. Interferon therapy can cause transient elevation of serum interleukin-1 alpha autoantibody levels.
Adult↗
[Riedel's lobe (caudal prolongation)].
Explore the source record for details and available documents.
Humans↗
[Dysmorphogenesis of intrahepatic bile duct].
Explore the source record for details and available documents.
Alagille Syndrome↗
Regulation of hepatocyte albumin and alpha 1-acid glycoprotein secretion by monokines, dexamethasone, and nitric oxide synthase pathway: significance of activated liver nonparenchymal cells.
To clarify the mechanism involved in regulating the secretion of albumin and alpha 1-acid glycoprotein by rat hepatocytes, we studied hepatocyte culture and cocultures of hepatocyte and liver nonparenchymal cells. The secretion of alpha 1-acid glycoprotein by hepatocytes was stimulated and that of albumin was inhibited by combinations of dexamethasone and monokines, especially by dexamethasone and interleukin-6. The secretion of these proteins was equally inhibited during stimulation by lipopolysaccharide in cocultures. The inhibitory effect of sinusoidal endothelial cells was smaller than that of Kupffer cells. This inhibition was partially abolished by blocking the nitric oxide synthase pathway in cocultured cells and was completely abolished by dexamethasone. In conclusion, the secretion of albumin and alpha 1-acid glycoprotein by hepatocytes was regulated by monokines, dexamethasone, and the inducible nitric oxide synthase pathway in hepatocytes and liver nonparenchymal cells in vitro.
Albumins↗
Morphological alterations of gap junctions in phalloidin-treated rat livers.
Morphological alterations in the pattern of liver cell gap junctions were examined in phalloidin-treated rats to assess the role of gap junctions in experimental intrahepatic cholestasis. Double-labelled fluorescent staining of gap junctions and F-actin were performed using a monoclonal antibody against rat hepatocyte connexin 32 and rhodamine-phalloidin. Immunoelectron microscopy, using the anti-connexin 32 antibody, freeze-fracture replica electron microscopy, and conventional electron microscopy were also performed. In phalloidin-treated rat livers, the specific immunofluorescent staining of connexin 32 was markedly decreased in the pericentral area after 1 day of phalloidin treatment and, after 5 days of phalloidin treatment, there was a decrease in connexin 32 staining in the entire hepatic lobule. On the other hand, F-actin staining at the cell periphery and at the bile canaliculi was markedly increased in the pericentral area of the hepatic lobule after 1 day of phalloidin treatment and in the entire lobule after 5 days of treatment. Immunoelectron microscopy showed that both sides of the cytoplasmic domains of gap junctions were stained with anti-connexin 32 antibody in controls, whereas, in cholestatic rats, only one side of the cytoplasmic domain of some gap junctions was stained with anti-connexin 32 antibody after 1 or 3 days of phalloidin treatment. No gap junctions were observed after 5 days of phalloidin treatment either by freeze-fracture replica electron microscopy or by conventional electron microscopy. These results indicate that with phalloidin treatment, hepatocyte gap junctions decrease, first in the pericentral area, and finally throughout the entire lobule.
Actins↗
Evaluation of hepatic proliferative activity in chronic liver diseases and hepatocellular carcinomas by proliferating cell nuclear antigen (PCNA) immunohistochemical staining of methanol-fixed tissues.
The proliferative activity of chronic liver diseases and hepatocellular carcinomas (HCCs) was studied by PCNA immunohistochemistry. Human liver tissues were obtained by surgical operation or needle biopsy, and PCNA was detected by immunohistochemistry. PCNA-labelling indices (PCNA-LIs) of methanol-fixed tissues corresponded with the incidence of S-phase cells previously reported, whereas paraformaldehyde-fixed tissues showed extremely high PCNA-LIs in all specimens. Therefore, methanol-fixed tissues were used for evaluation. The PCNA-LIs of the methanol-fixed tissues were: normal liver 0.78 +/- 0.38%, chronic persistent hepatitis 1.06 +/- 0.86%, chronic aggressive hepatitis 2A 1.01 +/- 0.50%, chronic aggressive hepatitis 2B 4.20 +/- 1.79%, inactive cirrhosis 0.81 +/- 0.49%, active cirrhosis 1.96 +/- 0.93%, HCC of Edmondson's type I 4.83 +/- 1.98%, type II 6.65 +/- 1.69%, and type III 38.7 +/- 30.6%. PCNA-positive cells showed little specific distribution; in periportal areas in chronic hepatitis, at the margins of pseudolobules in cirrhosis, and throughout the tumor in HCC. These findings indicated that proliferative activity increased during the progression of chronic hepatitis, but that it decreased at the stage of cirrhosis. In chronic liver diseases, the PCNA-LIs reflected hepatitis activity. HCC showed higher proliferative activity than liver cirrhosis, and the histological grade was correlated with the PCNA-LI.
Analysis of Variance↗
Hemodynamic effects of combined treatment with somatostatin analogue (SMS 201-995) and low-dose isosorbide dinitrate on portal hypertension in conscious cirrhotic rats.
The authors investigated whether combined treatment with the somatostatin analogue, SMS 201-995, and low-dose isosorbide dinitrate enhanced the hemodynamic effects of the individual agents on rats with thioacetamide-induced cirrhosis. Four groups of cirrhotic rats received SMS 201-995 (0.1 microgram.min-1.kg-1), isosorbide dinitrate (10 micrograms.min-1.kg-1), both agents, or placebo, respectively. Hemodynamics were measured serially in conscious rats, using a radioactive microsphere method. SMS 201-995 reduced portal venous inflow 21 +/- 4% and portal pressure 17 +/- 3%. Isosorbide dinitrate decreased portal venous inflow 20 +/- 4%, by inducing splanchnic vasoconstriction mediated by low pressure baroreflexes, and this agent also decreased portal pressure, by 14 +/- 2%. Portal venous resistance rose 7.6 +/- 3% with isosorbide dinitrate alone, but decreased 18 +/- 4% with combination therapy. This effect may have been induced by the pronounced vasodilatory effect of isosorbide dinitrate on the venous vasculature, since the reflex splanchnic vasoconstriction that occurs with low-dose isosorbide dinitrate disappears when this agent is combined with SMS 201-995. The decrease in portal pressure was more marked (22 +/- 4%) and changes in systemic hemodynamics were milder with the combined treatment. It was concluded that combination therapy with SMS 201-995 and low-dose isosorbide dinitrate may be beneficial for portal hypertension in liver cirrhosis.
Analysis of Variance↗
PreS1 deleted variants of hepatitis B virus in patients with chronic hepatitis.
Defective hepatitis B virus lacking 183 bases of the 3'-terminus part of the preS1 region was found in the sera of two patients with chronic hepatitis B virus infection. Results of sequencing analysis of samples with or without polymerase chain reaction yielded the same result, proving that this deletion was not due to an artifact obtained during polymerase chain reaction. One of the deletion ends lay in TCAGG that appeared five times in the genome of subtype adr and the other end was identified as TCAGG in direct repeats of the genome. The mutated hepatitis B virus became predominant in one patient's serum only after consecutive interferon therapy, suggesting that the deleted part might play a role in viral elimination from the circulation.
Base Sequence↗
Serum levels of macrophage colony stimulating factor (M-CSF) in liver disease.
We investigated the serum level of macrophage colony stimulating factor in acute and chronic liver disease. Levels of macrophage colony stimulating factor (mean +/- SD, ng/ml) were significantly higher in acute hepatitis (5.67 +/- 1.01, p < 0.01) and chronic active hepatitis (3.34 +/- 1.19, p < 0.01) than in healthy volunteers (1.90 +/- 0.25), asymptomatic hepatitis B virus carriers (1.98 +/- 0.40), and chronic persistent hepatitis (2.34 +/- 0.43). Levels of macrophage colony stimulating factor showed a highly significant correlation with the serum alanine aminotransferase levels in acute hepatitis (p < 0.01, rs = 0.903) and in chronic active hepatis (p < 0.01, rs = 0.672). Levels of macrophage colony stimulating factor in patients with cirrhosis (cirrhosis; 3.11 +/- 0.93 and hepatocellular carcinoma; 3.30 +/- 0.74) were significantly higher than in patients with chronic persistent hepatitis although the alanine aminotransferase levels were not significantly different. In cirrhosis, levels of macrophage colony stimulating factor correlated positively with the serum alanine aminotransferase levels (p < 0.05), total bilirubin levels (p < 0.05), and indocyanine green clearance (p < 0.05). An immunohistochemical study showed an increased number of macrophage colony stimulating factor positive mononuclear cells in portal areas in acute hepatitis. Our findings suggest that; (a) the serum levels of macrophage colony stimulating factor represent ongoing hepatocellular necrosis in acute and chronic liver disease, (b) the source of the increase in the serum macrophage colony stimulating factor levels in hepatic inflammation may be, in part, its production by infiltrating mononuclear cells in the liver, and (c) cirrhosis also causes elevated serum levels of macrophage colony stimulating factor.
Acute Disease↗