[Hepatocellular carcinoma complicating primary biliary cirrhosis--a case report and a review of the literature].
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Aged↗
Biomedical subjects
C Sato
Publications and source records attributed to C Sato.
Characterization of glutathione efflux from Hep G2 cells.
Previous studies have suggested that both cAMP-dependent signal transduction pathway and Ca2+/protein kinase C-dependent pathway are involved in GSH efflux from hepatocytes. In the present study, GSH efflux from Hep G2 cells, a human-derived hepatoma cell line, was further characterized. Both epidermal growth factor (0.1-10 ng/ml) and insulin (1 microgram/ml) significantly increased GSH efflux from Hep G2 cells. A fall in the membrane potential produced by the replacement of Na+ with equivalent K+ did not affect GSH efflux significantly. Neither ouabain, a Na+/K+ ATPase inhibitor, vanadate, a Ca2+ ATPase inhibitor, nor BaCl2, a K+ channel blocker, significantly affected the GSH efflux. Methionine (1mM) decreased GSH efflux from the cells, although total GSH content in the cells was not affected during the incubation time of 60 min. Signal transductions through tyrosine kinase-coupled receptors may also be involved in GSH efflux from hepatocytes.
Adenosine Triphosphatases↗
[Hepatocellular carcinoma associated with autoimmune hepatitis--a case report and a review of the literatures].
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Aged↗
A prospective study on hepatocellular carcinoma in liver cirrhosis: respective roles of alcohol and hepatitis C virus infection.
To assess the interaction of alcohol and HCV infection in hepatocarcinogenesis, we prospectively studied 447 patients with liver cirrhosis (LC) who presented to our out-patient clinics in a month; 163 patients with habitual drinking (AL-LC) who had taken more than 72 g alcohol per day (HCV positive 79 cases: HCV+AL; HCV negative 84 cases: AL); 176 with HCV infection but without alcohol intake; 39 with HB infection; and 82 with liver disease from other etiologies such as primary biliary cirrhosis (PBC). In the HCV group, HCC developed in 15 patients in the first year and 10 in the second year; the cumulative appearance rate was 11% and 16%, respectively. There was no difference in the HCC appearance rate between the two groups. In the AL group, the cumulative HCC occurrence rate was only 2% in the first year, and 2% in the second year. The appearance rate was significantly lower in the AL group compared with the HCV and the HCV+AL groups. One-hundred and fourteen patients (94 with HCV, 20 with HCV+AL) who had a history of blood transfusion more than 10 years ago were selected. A year-adjusted disease occurrence rate calculated by the Kaplan-Meier method showed that the HCV+AL group had a significantly higher disease occurrence rate than the HCV group. Theses results suggest that although alcohol alone does not become an independent risk factor for HCC from LC, it may accelerate the development of HCC caused by HCV, at least in the group with a history of blood transfusion.
Aged↗
A sodium channel model.
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Models, Structural↗
Structural diversity in the alpha 2-->8-linked polysialic acid chains in salmonid fish egg glycoproteins. Occurrence of poly(Neu5Ac), poly(Neu5Gc), poly(Neu5Ac, Neu5Gc), poly(KDN), and their partially acetylated forms.
alpha 2-->8-Linked polysialic acid (polySia) chains terminate O-linked oligosaccharide chains on Salmonidae fish egg polysialoglycoproteins (PSGPs). Expression of these surface PSGPs are developmentally regulated and the polySia epitope is functionally implicated in a number of distinct species-specific cell-cell recognition events during fertilization and early embryogenesis. To better understand the functional diversity of these PSGPs, structural studies of the polySia chains isolated from three genera and eight species of Salmonidae fish eggs were carried out by chemical, immunochemical, enzymatic, and 1H NMR methods. A remarkable degree of structural diversity was found, including differences in the N-acyl groups, i.e. N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc), and in the presence of either O-acetyl substitution at C4, C7, or C9 or O-lactyl substitution at C9. The presence of heteropolymers containing both Neu5Ac and Neu5Gc residues was also an unexpected finding. Accordingly, the different forms of alpha 2-->8-linked homo- and heteropolymers of these polySia structures include: poly(Neu5Ac), poly(Neu5Gc), poly(Neu5,chi Ac2), poly(Neu5Gc chi Ac), poly(Neu5Ac, Neu5Gc), poly-(Neu5Ac, Neu5,chi Ac2), poly(Neu5Ac, Neu5Gc chi Ac), poly(Neu5Gc,Neu5,chi Ac2), and poly(Neu5Gc, Neu5-Gc chi Ac), where chi represents the site of acetylation at carbon atom 4, 7, or 9. The significance of this new structural information, together with our recent finding of alpha 2-->8-linked polydeaminoneuraminic acid, poly(KDN), in the rainbow trout egg vitelline envelope, is that it demonstrates the natural occurrence of multiple forms of alpha 2-->8-linked polySia chains in Salmonidae fish glycoproteins that have not been previously described. The results also predict that a remarkable array of polysialylated glycoconjugates is yet to be discovered in animals other than teleost fishes.
Amino Acid Sequence↗
Expression of the hepatocyte growth factor receptor in the regenerating rat liver.
The c-met oncogene product is a cell-surface receptor, which ligand is believed to be the hepatocyte growth factor. We studied the expression of c-met oncogene in the regenerating rat liver after either partial hepatectomy or CCl4-induced liver injury. Northern blot analysis showed that after partial hepatectomy the transcripts of c-met decreased at 8 h, reached the minimum at 36 h, and returned to the steady level on the seventh day. In contrast with the hepatectomized liver, the transcripts of c-met increased after CCl4 treatment. These observations suggest that c-met transcription may be regulated differently depending on regeneration signals.
Amino Acid Sequence↗
Radiosensitization by a new potent nucleoside analog: 1-(1',3',4'-trihydroxy-2'-butoxy)methyl-2-nitroimidazole(RP-343).
PURPOSE: A new hypoxic cell sensitizer has been synthesized; this is a 2-nitroimidazole nucleoside analog having erythritol as a sugar moiety at the N-1 position of the imidazole ring (RP-343). Its possibility as a potent hypoxic cell sensitizer was compared with those of RP-170 and etanidazole. METHODS AND MATERIALS: Radiosensitization was tested in two murine tumors, EMT6 using in vitro and in vivo-in vitro assays and SCCVII using growth delay and TCD50 assays. Pharmacokinetic study was performed in Balb/c mice bearing EMT6 tumors and in Beagle dogs. LD50 of each sensitizer was obtained with ICR mice. RESULTS: As might be expected from the almost identical electron affinities of the three sensitizers, they were equally effective against hypoxic EMT6 cells in vitro. While having the lowest partition coefficient (0.035), RP-343 exhibited almost equally effective distribution to tumors and sensitizing radiation activity. An intravenous (i.v.) injection of 100 mg/kg of RP-343, RP-170 and etanidazole showed an almost equal sensitizer enhancement ratio (SER) of about 1.4 to solid EMT6 tumor under in vivo-in vitro assay and a virtually equal SER of 1.33-1.44 to solid SCCVII tumor under both tumor growth delay assay and TCD50 assay. A great advantage of RP-343 over RP-170 and etanidazole is its very much lower toxicity; their LD50 in mice were > 6.0, 4.3 and 4.8 g/kg, respectively, on i.v. injection. The lower toxicity of RP-343 was supported by its lower concentrations in the brain; the RP-343 AUC for brain was 0.43 times that of RP-170. Three indices were selected to compare the three nitroimidazoles. SER at 5% LD50 doses of RP-343, RP-170 and etanidazole was 1.66, 1.59 and 1.56. At the same toxicity levels, RP-343 was found to have better sensitization of solid tumors over both etanidazole and RP-170. The maximum tumor concentration/AUC for brain (Cmax,tumor/AUCbrain) ratios for RP-343 and RP-170 were 9.62 and 3.98. CONCLUSIONS: This extremely high ratio of RP-343 could explain its lower toxicity than RP-170 or etanidazole. The therapeutic risk index defined as D1.5/LD50 (D1.5 is the sensitizer dose to obtain the SER of 1.5 in vivo) for RP-343, RP-170 and etanidazole were 0.022, 0.033 and 0.036, respectively. Especially, the effectively lower therapeutic risk index for RP-343 presents the possibility of clinical advantage over etanidazole.
Animals↗
Down-regulation of ubiquitin gene expression during differentiation of human leukemia cells.
Ubiquitin, which is ligated covalently to target proteins for their acquisition of a variety of functions, is encoded by multiple unique genes in human cells: two distinct poly-ubiquitin genes with tandemly repeated sequences of 3 or 9 moieties and two mono-ubiquitin genes fused with small and large ribosomal proteins. We found that all classes of ubiquitin genes as well as the two genes encoding the ribosomal proteins S17 and L31 were expressed at abnormally high levels in various hematopoietic malignant tumor cells. In contrast, in vitro terminal differentiation of various immature leukemic cell lines, such as HL-60 promyelocytic leukemia cells and K562 erythroleukemia cells into monocytic, granulocytic and erythroid cells, induced by various agents was found to cause rapid and marked down-regulation of ubiquitin expression, irrespective of the cell type, direction of differentiation or type of signal. These findings suggest that the expressions of the multiple ubiquitin genes, coordinated with those of the ribosomal protein genes, are in a dynamic state during growth and differentiation of leukemia cells.
Cell Differentiation↗
Prevalence of hepatitis C virus infection among long-term hemodialysis patients: detection of hepatitis C virus RNA in plasma.
A high prevalence of anti-C100-3 antibodies has been reported in chronic hemodialysis patients. It is, however, unclear whether the results reflect true hepatitis C virus (HCV) infection in these patients, since false-positive results have been reported with this antibody assay. In the present study, plasma from 184 hemodialysis patients (110 males, 74 females) was examined for HCV-RNA by a reverse transcription-polymerase chain reaction method. Anti-C100-3 antibodies, second generation HCV antibodies, and anti-GOR antibodies were also examined by the respective EIAs. The positive rate of anti-C100-3 in the hemodialysis patients was 10.7% (20/184), which was significantly higher than the reported findings in the general population (P < 0.01). Using a second generation HCV antibody assay, the positive rate increased to 22%. HCV-RNA was detected in 15 of 184 patients (8.2%); 5 of 20 C100-3-positive patients (25%), and 10 of 164 C100-3-negative patients (6.1%). Serum alanine aminotransferase and gamma globulin levels were significantly higher in the patients with these HCV markers than those that were negative, while the history of blood transfusion was not related to the rate of the HCV markers. It is concluded that some hemodialysis patients have latent HCV infections that cannot be detected by currently available HCV antibody assays or routine biochemical liver function tests, and that the routes of transmission are not solely through blood transfusion.
Adolescent↗
Correlation of plasma hepatitis C virus RNA levels with serum alanine aminotransferase in non-A, non-B chronic liver disease.
The relationship between plasma hepatitis C virus (HCV) RNA levels, antibody positivity, and hepatocellular damage were studied in 41 patients with non-A, non-B chronic liver disease. The patients were placed into two groups according to the plasma levels of HCV-RNA: plasma HCV-RNA level was estimated as high when detected by a one stage polymerase chain reaction (PCR) and as low when detectable only after a two stage PCR. Anti-HCV (first and second generation assays) and anti-GOR were also measured. The mean alanine aminotransferase (ALT) level of the high HCV-RNA group was 115 +/- 62 IU/l, whereas that of the low HCV-RNA group was 59 +/- 37 IU/l (P < 0.05). Patients with ALT levels above 100 IU/l had invariably a high level of HCV-RNA. There were no differences in clinical features in relation to the presence of anti-GOR or anti-HCV. Circulating HCV-RNA levels but not anti-HCV or anti-GOR antibodies correlated with hepatocellular damage.
Aged↗
Asymptomatic arteriovenous malformation of the pancreas. Demonstration by Doppler ultrasonography and magnetic resonance imaging.
We reported a case of asymptomatic pancreatic AVM, incidentally found on routine ultrasonography and diagnosed noninvasively by means of Doppler ultrasonography and MRI. The diagnosis was confirmed by angiography. This is the first report to demonstrate the characteristics of pancreatic AVM by these two imaging techniques. They proved to be useful in identifying the vascular nature of AVM without the use of a contrast material, which is a definite advantage over DSA and CT. The quality of the image obtained was equivalent or superior to that obtained by DSA and contrast-enhanced CT. Doppler ultrasonography and MRI may serve as the primary imaging techniques of choice in suspected cases of AVM.
Angiography, Digital Subtraction↗
Alpha-smooth-muscle actin expression in normal and fibrotic human livers.
To determine the significance of the expression of alpha-smooth-muscle actin in the fibrotic human liver, normal and diseased livers were stained with anti-alpha-smooth-muscle-actin antibody by an immunoperoxidase method. Vitamin A-containing lipocytes were also identified by the modified Kupffer's gold chloride method. In the normal human liver, lipocytes as well as vascular smooth muscle cells expressed alpha-smooth-muscle actin. In alcoholic liver disease, there was an increase in the cells positive for alpha-smooth-muscle actin adjacent to the fibrotic areas, but the response of lipocytes to the gold chloride reaction diminished. In chronic hepatitis, the cells positive for alpha-smooth-muscle actin increased around the enlarged portal areas, and the response to the gold chloride reaction did not change appreciably. An increase in the cells positive for alpha-smooth-muscle actin was associated with the progression of hepatic fibrosis in the liver of patients with alcoholic liver disease and chronic hepatitis.
Actins↗
Hepatocellular carcinoma producing universal type of alkaline phosphatase.
We report on a 54-year-old man with hepatocellular carcinoma (HCC) associated with a marked elevation of serum alkaline phosphatase (ALP) levels. Serum ALP was biochemically similar to that of universal (liver/bone/kidney) type. The noncarcinomatous area revealed typical micronodular cirrhosis due to excessive alcohol consumption. By histochemical staining, ALP activity was demonstrated diffusely within the cytoplasm of carcinoma cells. Immunohistochemical observation of the carcinoma cells excluded the intestinal or placental type of ALP. Tissue extracts from the carcinomatous area had much higher ALP activities than those from a noncarcinomatous area, which also showed characteristics of the universal type. The present HCC is the first reported to produce and excrete the universal type of ALP.
Alkaline Phosphatase↗
Characterization of vasopressin-mediated GSH efflux from Hep G2 cells: significance of protein kinase C.
Vasopressin stimulated GSH efflux from Hep G2 cells. The maximal effect was observed at 10nM. Pretreatment with pertussis toxin or cholera toxin for 18 hr increased GSH efflux. Vasopressin-mediated GSH efflux was observed even in the cells pretreated with those compounds. Dibutyryl-cAMP or dibutyryl-cGMP enhanced GSH efflux although an additive effect of vasopressin was not observed. Glucagon and a phorbol ester independently increased GSH efflux while both compounds decreased the effect of vasopressin. Staurosporine, an inhibitor of protein kinase C, inhibited vasopressin-mediated GSH efflux. The effect of vasopressin was observed even in the absence of extracellular Ca2+. Vasopressin stimulates GSH efflux from Hep G2 cells and protein kinase C-dependent pathway may play a significant role in vasopressin-mediated GSH efflux.
Alkaloids↗
Possible transsynaptic cholinergic neuromodulation by ATP released from ileal longitudinal muscles of guinea pigs.
The effects of alpha, beta-methylene ATP (alpha, beta-mATP) and beta, gamma-methylene ATP (beta, gamma-mATP) on endogenous acetylcholine (ACh) release evoked by electrical nerve stimulation were evaluated in guinea-pig ileal longitudinal muscles. Release of ACh was measured with an HPLC-electrochemical detector system and release of ATP by luciferin-luciferase assay. Electrically evoked endogenous ACh release was reduced by both alpha, beta-mATP and beta, gamma-mATP at concentrations of 3 and 30 microM. The inhibitory effect of alpha, beta-mATP (30 microM) on ACh release was not detectable in the presence of theophylline (100 microM), a P1-purinoceptor antagonist, that itself enhanced ATP release. When exogenous ATP (0.1 microM) was added to the bath in which the ileal segment was suspended, it was rapidly metabolized, presumably by ecto-ATPase, and disappeared from the medium within 15 min. At 30 microM, alpha, beta-mATP induced ATP release in a suramin-sensitive but Ca(2+)- and atropine-insensitive manner, suggesting P2-receptor-mediated release of ATP from the smooth muscle. We conclude from these findings that alpha, beta-mATP and, probably, also beta, gamma-mATP, do not reduce ACh release by direct stimulation of presynaptic P1-purinoceptors, and that endogenous ATP released postjunctionally by these ATP analogs is decomposed metabolically to adenosine in the synapse and this adenosine triggers P1-purinoceptor sensitive neuromodulation of cholinergic transmission.
Acetylcholine↗
Implication of ATP released from atrial, but not papillary, muscle segments of guinea pig by isoproterenol and forskolin.
Effects of isoproterenol and forskolin, which increases intracellular cyclic AMP, on contraction and ATP release in atrial and papillary muscles of guinea pig were evaluated. In the electrically driven-left atrial muscle segments, isoproterenol and forskolin at 0.1 microM produced an ATP release coupled with a positive inotropic effect, the values of net ATP release at 5 min after these drugs being 5.20 +/- 0.59 and 5.37 +/- 0.55 nmoles/g wet weight, respectively. The forskolin evoked-ATP release was unaffected by prazosin plus propranolol or by guanethidine, implying that ATP is released from non-neuronal origin. In contrast, in papillary muscle segments, the test cardiotonics did not elicit any ATP release despite producing contractile response similar to that in atrial preparations. However, there is no difference in ectoATPase activities of both tissues. Adenosine added exogenously inhibited electrically evoked-contraction of the atrium, but not that of the papillary, although inhibitions by verapamil of the contractions were approximately equal in these preparations. These findings suggest that cardiotonics such as isoproterenol produce a liberation of ATP from auricle muscles, but not from ventricle muscles, and that the liberated ATP may mainly be catabolized to adenosine by ectoenzymes and the resultant nucleoside may serve as a functional modulator through stimulation of pre or postsynaptic A1-receptors.
Adenosine↗
Role of lipid peroxidation in acetaminophen-induced hepatotoxicity: comparison with carbon tetrachloride.
The effect of acetaminophen on lipid peroxidation in vivo and in vitro was studied in rat liver and the data were compared with those with carbon tetrachloride. Carbon tetrachloride increased diene conjugates in vivo and thiobarbituric acid reactive substance production in vitro in the liver microsomal incubation. These changes were further enhanced by ethanol that has previously been shown to increase carbon tetrachloride-induced hepatotoxicity. On the other hand, acetaminophen did not increase diene conjugates in vivo and inhibited thiobarbituric acid reactive substance production in vitro. These effects were minimally affected by ethanol which has previously been shown to inhibit acetaminophen-induced hepatotoxicity. Thus, lipid peroxidation may play a minimal role in acetaminophen-induced hepatotoxicity in contrast with carbon tetrachloride-induced hepatotoxicity.
Acetaminophen↗