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  • 1
    ISSN: 1573-2568
    Schlagwort(e): chronic hepatitis C ; IFN-β ; therapy ; HCV-RNA load ; HCV-NS5A ; CRT-PCR
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Virological sustained response (SR) is achieved in 31–49% of patients with chronic hepatitis C with combination therapy using interferon (IFN) -α and ribavirin for 24–48 weeks. However, as a period of 24–48 weeks is a burden for patients, we investigated the effect of daily intravenous administration of natural IFN-β for 12 weeks in this study. In all, 112 patients were enrolled and received a daily administration of 6 MU of natural IFN-β intravenously for 12 weeks. Serum HCV-RNA before treatment was assessed by the competitive reverse-transcription polymerase chain reaction assay. The patients were divided into two groups according to pretreatment viral load: the low viral load group (N = 25, 〈6.3 × 105 copies/ml), and the high viral load group (N = 87, ≥6.3 × 105 copies/ml) who were additionally administered IFN-β thrice weekly for subsequent 14 weeks at the patients' request. Virological SR was obtained in 37% (41/112) of all the patients; 88% of those with a low viral load, and 22% of patients with a high viral load. Virological SR was attained in 21% of patients with HCV subtype 1, and in 67% of those with subtype 2a. In patients with HCV subtype 1b, virological SR was obtained in patients with the mutant-type (≥4 amino acid mutations in the NSSA2209–48) having a low viral load (4/4), but not in those having a high viral load (0/3). The results suggest that a daily intravenous administration of natural IFN-β for 12 weeks showed high therapeutic efficacy in patients with a low viral load despite the shorter treatment period and that the therapeutic efficacy depends on viral load rather than on the number of NS5A2209–48 amino acid mutations.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1573-2568
    Schlagwort(e): ethanol ; hepatocytes ; chemotactic factor ; neutrophils ; antiallergic agents ; prednisolone
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In an attempt to clarify a mechanism of neutrophil infiltration in the liver of alcoholics and possible therapeutic effect of antiallergic agents on accumulation of these cells in the liver, we investigated chemotaxis of neutrophils by stimulation of a chemotactic factor released from rat hepatocytes exposed to ethanol. When hepatocytes were incubated with more than 30 mM ethanol for 24 hr, chemotactic activity for both rat and human neutrophils was demonstrated in the conditioned medium. An enhanced chemotactic activity of the conditioned medium was reduced in the presence of antibody against KC/gro protein, one of the interleukin-8-related cytokines in rodents. Antiallergic agents such as azelastine or ketotifen at a concentration of 〉0.01 µM markedly reduced chemotaxis of neutrophils. Prednisolone at a concentration of 〉10 µM also reduced chemotaxis of neutrophils. These results suggest that neutrophil accumulation in the liver of human alcoholics could be induced by a chemotactic factor produced by the ethanol-treated hepatocytes and that antiallergic agents could be effective against the extent of alcoholic hepatitis by reducing chemotaxis of neutrophils.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1573-2568
    Schlagwort(e): colon 38 adenocarcinoma ; asialo GM1-positive cells ; natural killer cells ; killed streptococcal preparation ; hepatic metastasis ; splenectomy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We have previously demonstrated that administration of killed streptococcal preparation (OK432), a biological response modifier, increased the number of asialo GM1-positive cells in the liver, enhanced NK activity of hepatic mononuclear cells, and reduced the number of hepatic metastases of colon 38 adenocarcinoma that were inoculated into the superior mesenteric vein of C57BL/6 strain mice. In the present study, to clarify the role of the spleen in immune surveillance of the liver, the effect of splenectomy on hepatic metastasis of colon carcinoma and on hepatic NK activity has been examined. The number of hepatic metastasis increased in the splenectomized mice, compared with that in sham-operated mice. Administration of OK432 increased the number of asialo GM1-positive cells in the liver and enhanced NK activity of hepatic mononuclear cells in both groups, but NK activity of hepatic mononuclear cells in the splenectomized mice was less than that of the sham-operated mice. An enhanced NK activity of these cells was abolished by treatment with anti-asialo-GM1 antibody plus complementin vitro. Interleukin-2 mRNA expression was increased in the spleen 2 hr after OK432 administration and persisted until 8 hr, but was scarcely noted in the liver. On the other hand, NK activity of hepatic mononuclear cells in the asialo GM1-positive cell-depleted (previous administration of antiserum against asialo GM1) mice was enhanced after OK432 administration in the sham operated and splenectomized mice, but an enhanced NK activity in these mice was only partially or not at all abolished by treatment with anti-asialo GM1 antibody plus complementin vitro, respectively. These results suggest that the spleen could play an important role in an immune surveillance of the liver. In addition, OK432 first enhanced NK activity of hepatic mononuclear cells, which are sensitive to the antibody against asialo GM1. However, when asialo GM1-positive cells were depleted, OK432 enhanced NK activity of hepatic mononuclear cells, which are resistant to anti-asialo GM1 serum.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    ISSN: 1573-2568
    Schlagwort(e): KUPFFER CELLS ; HEPATOCYTES ; NITRIC OXIDE SYNTHASE ; mRNA ; CELLULAR COMMUNICATION
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract To investigate the cellular communication in theliver, nitric oxide (NO) production by sinusoidal cellsand hepatocytes by stimulation with cytokines andKupffer cell-conditioned medium was quantitatively analyzed. NO production by the cells wasmeasured by the Griess reaction, and nitric oxidesynthase (iNOS) transcription level by a competitiveRT-PCR assay using mutant iNOS mRNA as a standard. NOproduction and iNOS mRNA transcriptional levels in Kupffercells were markedly increased by stimulation withlipopolysaccharide (LPS) and interferon-γ(IFN-γ), and moderately by interleukin-1β(IL-1β). NO production by hepatocytes was notsignificantly enhanced by LPS, but was markedly enhancedby IL-1β or the combination of tumor-necrosisfactor-α (TNF-α) and IFN-γ. HepatocyteNO production and iNOS mRNA levels were markedly enhanced bythe LPS-activated Kupffer cell conditioned medium, butthese effects were reduced by heat treatment or anti-TNFantibody. Although NG-monomethyl-L-arginine acetate and dexamethasone reduced NO productionby the cells, the iNOS mRNA level was reduced bydexamethasone only. Gel-shift assay showed NF-κBactivation in hepatocytes during this activation. These data reinforce the importance of cellularcommunication between sinusoidal cells andhepatocytes.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 5
    ISSN: 1573-2568
    Schlagwort(e): COLORECTAL POLYP ; MICROSATELLITE INSTABILITY ; HEREDITARY NONPOLYPOSIS COLORECTALCANCER ; MISMATCH REPAIR GENE ; TRANSFORMING GROWTH FACTOR-β TYPE IIRECEPTOR
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Mutations in the transforming growthfactor-β type II receptor (RII) gene that remainuncorrected due to mutation and inactivation of mismatchrepair genes play an important role in hereditarynonpolyposis colorectal cancer (HNPCC) and in a subset ofsporadic colorectal cancers. Some colorectal cancersdevelop from colorectal polyps. To elucidate the role ofthe RII gene in the generation of colorectal polyps, we analyzed 137 colorectal polyps from 100patients for RII mutations and microsatelliteinstability (MSI). MSI was detected in three of 36polyps from 25 patients. For one of these three polyps,the mobilities of the PCR products between polyp and nonpolyptissues was different for only one microsatellitemarker, and for the other two polyps the mobilities weredifferent for more than two markers. These two polyps were obtained from one patient with ascendingcolon carcinoma and suspected HNPCC based on hisclinical profile and family history. An RII mutation wasdetected in only one of these two polyps. RII may play a minor role in sporadic colorectalpolyps. RII gene analysis in colorectal polyps may be auseful screening measure for potential HNPCCpatients.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 6
    ISSN: 1435-5922
    Schlagwort(e): gastric choriocarcinoma ; gastric adenocarcinoma ; human chorionic gonadotropin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A 63-year old woman who had experienced melena for 2 weeks was admitted to Tokyo University Hospital. Gastric adenocarcinoma was diagnosed endoscopically and histologically, and a total gastrectomy was performed soon thereafter. Pathological examination of the resected stomach revealed choriocarcinoma of the stomach. Although chemotherapy was administered after surgery, she died 3 months after admission. Autopsy confirmed the diagnosis of primary gastric choriocarcinoma, a rare, but highly malignant tumor. It is characteristic; macroscopically it forms a necrotic mass with bleeding, and microscopically it often consists of adenocarcinoma and choriocarcinoma. Since its prognosis is extremely poor, we must take into account the possibility of primary gastric choriocarcinoma when a hemorrhagic gastric tumor with necrosis is found.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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