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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of gastroenterology 30 (1995), S. 731-738 
    ISSN: 1435-5922
    Keywords: stellate cell ; endothelin ; fibrosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To elucidate the role played by hepatic sinusoidal cells in the regulation of the circulatory status in the liver, the effect of endothelins (ETs) on primarycultured stellate cells was examined. Kinetic analysis with125I-labeled ET-1 revealed that stellate cells have ET receptors with a Kd value of 141 pM and a Bmax of 12.3 fmol/105 cells. ET-1,-2, and-3 dose-dependently increased inositol monophosphate (InsP) levels in stellate cells with an EC50 of 0.53, 1.63, and 1.88 nM, respectively. Binding of125I-labeled ET-1 to stellate cells and the ET-enhanced InsP formation were suppressed by preincubating the cells with 10 nM of unlabeled ET-1 or ET-3 for more than 3 h, indicating down-regulation and desensitization of ET receptors by homologous ligands. Binding of ETs to surface receptors induced a marked contraction of stellate cells. Stellate cells rapidly reacted to ETs, as detected by the flexible silicone-rubber-membrane method; 78%, 73%, and 58% of the stellate cells contracted 2.5 min after the addition of 10 nM of ET-1, ET-2, or ET-3, respectively. On the other hand, ETs also triggered a long-lasting contraction of the cells, as revealed with hydrated collagen gels. The ET-induced contraction of stellate cells decreased the diameter of the collagen lattice by about 60%, and this action was inhibited either by cytochalasin B or by H-7, a protein kinase C inhibitor. These and other results suggest that ETs induced cell contraction by some mechanism that involved protein kinase C.
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  • 2
    ISSN: 1435-5922
    Keywords: Key words: fulminant hepatic failure ; TT virus ; hepatitis virus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: A novel virus (TT virus) was isolated from patients with posttransfusion hepatitis of unknown etiology. We studied the prevalence of TT virus in 26 patients with fulminant hepatic failure without risk factors, including blood transfusion, and also examined 106 healthy blood donors as controls. We assayed serum TT virus DNA by seminested polymerase chain reactions and also examined the genotypes of this virus. Serum was obtained at admission from patients with fulminant hepatic failure. Serum samples at admission from seven (27%) of the 26 patients were positive for TT virus DNA. There were no differences in clinical findings, duration from onset to coma, or results of laboratory tests in patients with and without TT virus DNA. However, all 7 patients with TT virus died, whereas 9 of the 19 patients without TT virus died. The outcome for patients with fulminant hepatic failure and TT virus was significantly worse than for patients without the virus (P = 0.0227). TT virus was also detected in 29 (27%) of the 106 healthy blood donors. The genotype of the TT virus was mainly 1a in both groups. There were no differences in the rate of positivity and the genotypes of TT virus between patients with fulminant hepatic failure and healthy blood donors. TT virus infection may not cause severe hepatitis, such as fulminant hepatic failure, but it may indicate a poor outcome in such patients.
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  • 3
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Although there have been many studies of the risk factors for recurrence after resection of hepatocellular carcinoma (HCC), the subjects were patients with various viral status in the previous studies, and hepatitis C viremia has not been evaluated. We investigated risk factors, including hepatic C viremia and histologic findings of noncancerous hepatic tissue, for recurrence after resection of hepatitis C virus (HCV)-related HCC. A total of 223 patients who underwent liver resection for HCV-related HCC were studied. HCV viremia, laboratory data, degree of HCC malignancy, histologic findings in noncancerous hepatic tissue, preoperative interferon therapy, and operative methods were evaluated for recurrence risk by univariate and multivariate analyses. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin, and the proportion of patients with a high histologic activity score (mild to severe active hepatitis) were significantly higher in patients with HCV viremia than in those without viremia. Serum albumin was significantly lower in patients with HCV viremia. By univariate analysis, older age (〉 65 years old), HCV viremia, elevated AST (〉 40 IU/L) and ALT (〉 45 IU/L), large tumors (〉 40 mm), multiple HCCs, moderately or poorly differentiated HCC, portal invasion, mild to severe active hepatitis, and lack of preoperative interferon therapy were risk factors for recurrence. Multivariate analysis showed that older age, HCV viremia, high AST, multiple HCCs, and portal invasion were independent risk factors. For HCV-related HCCs, not only the degree of maliganacy of the HCC but also HCV viremia and active hepatitis are risk factors for recurrence.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2307
    Keywords: Biliary epithelial cells ; DNA polymeraseα ; Ductular proliferation ; Immunohistocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The proliferative activity and ultrastructural characteristics of proliferating biliary epithelial cells were analysed immunohistocytochemically in 39 biopsied liver specimens from patients with acute viral hepatitis, chronic hepatitis and liver cirrhosis using a monoclonal antibody against DNA polymerase α (DNA-PA). In acute viral hepatitis with perivenular confluent necrosis, proliferation of typical bile ducts was found frequently in portal areas. In chronic aggressive hepatitis and cirrhosis, ductular proliferation of both typical and atypical forms was found in enlarged portal and periportal areas and in confluent necrotic areas. The number of proliferating biliary epithelial cells that stained positive for DNA-PA was small. There were very few positively stained cells in atypical bile ducts in confluent necrotic areas of cirrhosis. Atypical bile ducts seen in chronic aggressive hepatitis, cirrhosis and acute hepatitis with confluent necrosis were positively stained for both cytokeratins 8 and 19. In cirrhosis, the number of stained biliary epithelial cells in typical bile ducts was larger than the number of such cells in atypical bile ducts (P〈 0.01). By electron microscopy, the cells positively stained for DNA-PA were mostly so-called clear cells with irregular nuclei containing coarse nucleoplasm, and a few small cells with scanty cytoplasm and few organelles.
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  • 5
    ISSN: 1432-2307
    Keywords: Hepatocellular carcinoma ; Apoptosis ; Transforming growth factor-α
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A cell line derived from a Japanese man with hepatocellular carcinoma was established in culture and designated OCUH-16. The cell line has the morphological and chromosomal features of hepatocellular carcinoma cells and has a short doubling time (≈33 h). OCUH-16 cells were shown to express transforming growth factor-α, (TGF-α) in addition to albumin, DNA polymerase-α, c-JUN, and the retinoblastoma gene product. Electron microscopy revealed TGF-α immunoreactivity associated with the cell membrane, but TGF-α was not detected in medium conditioned by OCUH-16 cells by enzyme-linked immunosorbent assay. Reverse transcription and polymerase chain reaction analysis revealed the presence of TGF-α messenger RNA in these cells. Culture of OCUH-16 cells in the presence of a neutralizing antibody to TGF-α inhibited cell proliferation and induced many cells to undergo apoptosis (programmed cell death). These observations suggest that endogenous TGF-α is necessary for OCUH-16 cell growth.
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  • 6
    ISSN: 1432-0878
    Keywords: Key words: Heat-shock protein 47 ; Nonparenchymal liver cells ; Stellate cells ; Fibrosis ; Mouse (ICR)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Expression of heat-shock protein 47 in intact and fibrotic liver and in hepatic constituent cells was investigated in mice. Immunohistochemical study of intact liver and Western blot analysis of the protein from isolated liver cells revealed that stellate cells and smooth muscle cells of interlobular vessels, but not hepatocytes, Kupffer cells, or endothelial cells, expressed heat-shock protein 47. The protein was found in both vitamin-A-storing stellate cells and myofibroblast-like cells. The amount of the protein in cultured stellate cells was reduced by dexamethasone but was not regulated by quercetin, transforming growth factor β, interferon γ, or retinoic acid. In CCl4-treated or bile-duct-ligated mouse liver, the number of cells positive for heat-shock protein 47 markedly increased in the centrilobular area or around the periportal area, respectively, and the level of heat- shock protein 47 also increased.
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  • 7
    ISSN: 1619-7089
    Keywords: Hepatocellular carcinoma ; Factor analysis ; Radionuclide angiography ; phytate Tc99m
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined the usefulness of factor analysis for the diagnosis of hepatocellular carcinoma by analysis of the data obtained by radionuclide angiography. The data could be separated into two factors, a hepatic phase (hepatic artery and portal vein) and an arterial phase (aorta and kidney). In patients with hepatocellular carcinoma, the factor of the tumor is included in the arterial phase, so that the cancerous region could be differentiated from the noncancerous region. The ratio of the radioactivity of the cancerous region to the noncancerous region was used to estimate the blood flow of the tumor region.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Digestive diseases and sciences 38 (1993), S. 612-618 
    ISSN: 1573-2568
    Keywords: chronic hepatitis C ; interferon-α-2b ; hepatitis C virus RNA ; 2′, 5′-oligoadenylate synthetase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A comparative study of three different high-dose regimens of interferon-α-2b (IFN) was conducted in patients with chronic hepatitis C to determine which was better at obtaining a sustained remission. A total of 126 patients were assigned randomly to one of three groups: group A was given 10 million international units (MIU) of IFN six times a week for eight weeks; group B was given 10 MIU IFN six times a week for four weeks followed by three times a week for an additional eight weeks; group C was given 10 MIU IFN six times a week for two weeks followed by three times a week for 12 weeks. The total dose administered to each group was 480 MIU/patient. Only the dosing schedule varied among the three groups. Among 98 efficacy-evaluable patients, a sustained alanine aminotransferase (ALT) response, defined as persistent normalization of the ALT for greater than six months after the termination of treatment, was achieved in 21.2% (7/33) of group A, 42.3% (11/26) of group B, and 54.5% (18/33) of group C patients. Similarly, a sustained loss of measurable serum hepatitis C virus RNA was observed in 28.6% (8/28) of group A, 40.9% (9/22) of group B, and 48.3% (14/29) of group C patients. Based upon these data, it can be concluded that 10 MIU of IFN administered six days a week for two weeks followed by three times a week for an additional 12 weeks produces the highest rate of both biochemical and virological responses to IFN therapy in patients with chronic HCV.
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  • 9
    ISSN: 1573-2568
    Keywords: stellate cell ; myofibroblastic cells ; cAMP ; 3-isobutyl-1-methylxanthine ; α-smooth muscle actin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Stellate cells isolated from rat liver and cultured on uncoated plastic plates in serumcontaining medium started proliferating and transforming to myofibroblastic cells. However, stellate cells did not proliferate when cultured in the presence of 3-isobutyl-1-methylxanthine or dibutyryl cAMP (dBcAMP). These substances significantly reduced [3H]thymidine incorporation of the proliferating cells. Morphologically, stellate cells cultured in the presence of 3-isobutyl-1-methylxanthine or dibutyryl cAMP kept well-developed processes and lipid droplets while untreated cells exhibited myofibroblastic characteristics. Western blot analysis and immunocytochemical studies revealed that 3-isobutyl-1-methylxanthine and dBcAMP suppressed the expression ofα-smooth muscle actin in stellate cells. 3-isobutyl-1-methylxanthine increased the cellular levels of cAMP from a basal value of 0.7 ± 0.1 to 8.5 ± 1.7 pmol/well in stellate cells. Thus, 3-isobutyl-1-methylxanthine and dBcAMP inhibit the myofibroblastic transformation of stellate cellsin vitro in some cAMP-related mechanism.
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  • 10
    ISSN: 1573-2568
    Keywords: intercellular adhesion molecule-1 ; CD18 ; ischemia–reperfusion injury
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Submucosal injection of endothelin (ET) -1 induces gastric ulcer. We investigated the roles of neutrophils and adhesion molecules (intercellular adhesion molecule (ICAM)-1 and CD18) in the development of ET-1-induced ulcers in rats. Ulcers were induced by submucosal injection of ET-1. Rats were injected with anti-neutrophil serum or F(ab")2 fragments of irrelevant mouse IgG2a (control), anti-ICAM-1 antibody, or anti-CD18 antibody. Ulcer tissues were subjected to measurement of myeloperoxidase (MPO) activity, ulcer size, and immunohistochemical study. Within 3 hr, arterial vasoconstriction and vascular congestion were observed at sites of ET-1 injection. By 6 hr, vascular congestion had disappeared, and ICAM-1 expression had markedly increased in venules in deep portions of the mucosa and submucosa, accompanied by an increase in the number of CD18-positive neutrophils. By 48 hr, ulcers that extended into the submucosa had developed. In controls, MPO activity gradually increased and was maximal by 6 hr. Neutrophil depletion, and immunoneutralizing of ICAM-1 and CD18 inhibited the increase in MPO activity, and decreased ulcer sizes measured at 48 hr. In conclusion, ET-1 causes ischemia–reperfusion injury, and neutrophil accumulation after reperfusion mediated by the ICAM-1-CD18 pathway may be important in the development of ET-1-induced gastric ulcer.
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