ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1993.tb00607.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

ABSTRACT—Studies were undertaken to examine the effect of recombinant human transforming growth factor beta 1 (rTGF‐β1) on cellular and humoral immune responses of peripheral blood mononuclear cells (PBMC) from patients with chronic hepatitis B. The addition of TGF‐β1 caused a significant dose‐dependent inhibition of hepatitis B (HB) core Ag‐stimulated interferon‐γ and antibody to HB core Ag production and proliferation of PBMC from chronic hepatitis patients and HB‐immune donors. TGF‐β1 also induced a significant reduction in pokeweed mitogen‐stimulated IgG and IgM production, as well as phytohemagglutinin p‐stimulated proliferative response of PBMC. The degree of inhibition of TGF‐β1 did not differ between antigen‐specific and ‐nonspecific cellular and humoral immune responses, and between control individuals and patients. Pretreatment study with TGF‐β1 showed that the activities of T cells, B cells and monocytes were similarly inhibited. Further, TGF‐β1 inhibited activities of HLA class I antigen‐matched cytotoxic T cells from patients with chronic hepatitis B for HBV DNA‐transfected HepG2 cells in a51Cr release assay. The results suggest that TGF‐β1 may play a role in the regulation of antigen‐dependent and ‐independent immune

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1993.tb00608.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

ABSTRACT—The diagnosis of acute hepatitis C (AHC) often can only be suspected because current serologic tests remain negative for over 3 months. Because histologic features might provide useful clues, we reviewed 85 liver biopsy specimens from 85 patients with acute viral hepatitis, comparing 22 cases of AHC with 23 cases of acute hepatitis A (AHA), 30 cases of acute hepatitis B (AHB), and 10 cases of acute hepatitis non‐A, non‐B, non‐C (AHNC). AHC was characterized by dense portal lymphoid aggregates (7 cases) and Poulsen‐Christoffersen‐type cholangitis (8 cases); these lesions were not found in any other type of acute viral hepatitis, and thus appeared to be diagnostic. Sinusoidal inflammatory infiltrates also were common in AHC, particularly in biopsy specimens obtained during the early phase of the disease. These inflammatory infiltrates did not appear to affect adjacent hepatocytes. Necrosis in AHC usually was spotty and accompanied by mixed inflammatory cells. In AHNC, necrosis was also spotty but, as an added feature, pigmented macrophages predominated in them. In AHA, necrosis was predominantly periportal, whereas in AHB, severe zone‐3 necrosis predominated. Fatty changes were predominantly microvesicular; they were common in AHC but were also found in other groups. Collectively, the described histologic features allowed diagnosis of AHC in biopsy specimens with reasonable confidence. However, histologic findings failed to predict the prognosis in ind

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1993.tb00609.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

ABSTRACT—To assess the effect of long‐term alfa interferon therapy (12 months) on liver histology of chronic hepatitis C, we studied 61 treated patients, and compared their outcome with 28 untreated cases followed as controls. A liver biopsy was taken from all patients, before (month 0) and after the completion of the treatment or the control period (month 12). A third liver specimen taken at month 24 was available in 29 treated cases. Liver biopsies were blindly graded following Knodell's method. In 33 out of the 61 treated patients (54.1%), aminotransferase levels became normal shortly after starting therapy and remained within normal values until the end of treatment (sustained response). Nine (27%) sustained responders relapsed after interferon discontinuation, while the remaining 24 (73%) continued with normal aminotransferase values during follow‐up (16.8 ± 9.9 months). All histological parameters, except fibrosis, improved significantly after 12 months of therapy (periportal necrosis, month 0: 2.7 ± 1.0, month 12: 1.6 ± 1.1, p<0.0001; lobular damage, month 0: 2.5 ± 1.1, month 12: 1.4 ± 0.9, p<0.0001; portal inflammation, month 0: 3.6 ± 0.5, month 12: 3.0 ± 0.9, p<0.0001). Histological improvement was especially marked in patients who did not relapse, although those who relapsed and partial responders also improved. Overall histological diagnoses improved in most patients. A sustained response to inteferon was predicted by high periportal and lobular scores, and by a low fibrosis score on the pretreatment liver biopsy. At 24 months, histological improvement persisted in patients without posttreatment relapse, while liver inflammation had returned to pretreatment levels in the rem

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1993.tb00610.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

ABSTRACT—Altered expression of asialoglycoprotein (ASGP) receptors on hepatocytes has been reported during hepatic neoplasia mostly in animal models. In this study, we examined immunohistochemically the distribution of the ASGP receptor in humans with various liver diseases, including ten cases of hepatocellular carcinoma (HCC). In livers of acute hepatitis, chronic hepatitis, cirrhosis and the non‐cancerous tissues (mostly cirrhosis) adjacent to HCC, the receptor was present in its normal distribution, i.e. mostly along the sinusoidal margin and partly on the lateral surface of hepatocytes. In four of six well‐differentiated HCCs, the receptor was also normally distributed on the plasma membrane; by immunoelectron microscopy, it was seen in the endoplasmic reticulum and in pits in the plasma membrane but not on bile canaliculus‐like structures, suggesting that it was synthesized, transported, and integrated into the plasma membrane in a polar manner. In contrast, there was no surface expression of the ASGP receptor in the remaining six HCCs (two well‐differentiated and four poorly differentiated). In two of the poorly differentiated HCCs, the receptor, although absent from the cell surface, was prominent in the endoplasmic reticulum, suggesting disturbed transport of the ASGP receptor to the cell surface. When we examined proliferative activity of HCCs by immunohistochemical labeling of DNA polymerase a, HCCs with high percentages (above 30%) of DNA polymerase α‐positive cells had lost the cell‐surface expression of the receptor. Thus, the expression of the ASGP receptor in human HCC appears to be closely related to differentiation and proliferative activity of t

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1993.tb00611.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

ABSTRACT—IGF‐1 and IGF‐2 stimulate dose‐dependently DNA synthesis of nonconfluent cultures of rat fat storing cells, a nonparenchymal type of liver cells pathogenetically involved in the generation of liver fibrosis. Maximum stimulation of [3H] thymidine incorporation of about 2.6‐fold above control was reached with 100 ng/ml IGF‐1 and 500 ng/ml IGF‐2, respectively. The DNA synthesis promoting action of both IGF‐1 and IGF‐2 was most efficiently potentiated by hepatocyte‐conditioned medium raising the stimulatory effect up to 21‐fold above control cultures. Lysate of hepatocytes (up to 15 μg protein/ml) was not effective in potentiating the effect of IGF‐1. IGF‐1 is bound to free carrier protein(s) present in the medium of hepatocytes, but obviously absent in cell lysate. Three molecular weight fractions in the ranges of 67 kd, 35 kd, and 25 kd could be identified in the medium, which potentiate the growth‐promoting effect of IGF‐1. Applying Western ligand blot analysis, three molecular size classes of IGF‐1 binding proteins in the conditioned media of rat hepatocytes were determined. The major binding protein had a Mrof 28–34 kd, a minor portion was localized at Mr24 kd, whereas trace binding affinities were found at Mrof about 95 kd. It is suggested that IGF‐1, IGF‐2 and the complex array of IGF‐binding proteins secreted by hepatocytes might be involved in the paracrine regulation of growth of fat storing cells.Nonstandard abbreviations: BSA, bovine serum albumin; FCS, fetal calf serum; FSC, fat scoring cells; IGF, insulin‐like growth factor; IGFBP, IGF‐binding protein; Mr, relative molecular weight; PAGE, polyacrylamide gel electrophoresis; PBS, phosphate‐buffered saline; PCcM, hepatocyte‐conditioned medium; SD

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1993.tb00612.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

ABSTRACT—Studies were undertaken to evaluate the relationship between the immune responses and the effectiveness of interferon‐α treatment in 21 patients with HBeAg‐positive chronic active hepatitis. Peripheral blood mononuclear cells (PBMC), obtained on four occasions during an 8‐week course of IFN‐α therapy, were cultured with recombinant HBcAg, purified HBeAg or pokeweed mitogen (PWM). During follow‐up for 6 months after therapy, clearance of serum HBeAg was observed in eight patients designated as responders. Immunological responses of PBMC obtained before treatment did not differ between responders and non‐responders. In responders, IFN‐γ and anti‐HBc production was depressed during therapy, but recovered to above the pretreatment level at the end of and/or after cessation of therapy, while lymphocyte proliferation was enhanced during therapy with a subsequent decline to baseline value. In non‐responders, such changes were modest throughout the study, and anti‐HBc response remained decreased even after cessation of therapy. These results indicate that PBMC of responders have immunologically different responses to IFN‐α therapy when c

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1993.tb00613.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

ABSTRACT—Nuclear protooncogene and alpha‐fetoprotein gene expression is stimulated in hepatocytes during liver regeneration and by various growth factorsin vitro.Metabolic adaptation of hepatocytes has been implicated in such gene reprogrammation. We examine here whether induction of an acute inflammation, a physiological situation of important metabolic adjustments, also triggers activation of nuclear oncogenes and of the AFP gene in rat liver.C‐fos, c‐junandc‐mycmRNA accumulated on Northern blots between 4–12 h of inflammation and the steady‐state level of two small alpha‐fetoprotein transcripts characteristic of the adult liver increased at 4 h and 24 h of inflammation.In situhybridization showed accumulation of the mRNA of the four genes studied in all hepatocytes, without any zonal lobular heterogeneity.3H‐histoautoradiography and mitotic counts indicated an inhibition of DNA synthesis and mitosis, prolonged for at least 48 h after inflammation. Thus acute inflammation triggers the activation of nuclear protooncogenes and alpha‐fetoprotein gene in hepatocytes, but this activation is not followed by passage into th

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1993.tb00614.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1993.tb00615.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1993.tb00616.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY