摘要:

Abstract:Methods for the evaluation of the four antimitochondrial antibody subtypes in primary biliary cirrhosis ‐ anti‐M2, ‐M4, ‐M8, ‐M9 ‐ are described. The importance of the application of different preparations for the demonstration of complement fixing antibodies and the detection of antibodies by ELISA or Western blotting is emphasized. Complement fixing antigens can be prepared by discontinuous isopynic sucrose density gradient centrifugation using mitochondrial subfractions derived either from beef heart (M2), rat liver (M4), or pig kidney (M8). Anti‐M9 antibodies do not fix complement. For ELISA, the pyruvate dehydrogenase or the AT‐Pase‐associated antigen fraction (M2), the sulfite oxidase fraction (M4), and the chromatographically purified M8‐fraction should be used. The same antigen fractions are suitable for Western blotting, but anti‐M4 and anti‐M8 cannot be visualized by this method. For the demonstration of anti‐M9 by ELISA and Western blotting a purified fraction prepared from rat liver has to be applied. Correlating antimitochondrial antibody‐subtypes with clinical condition and the natural course, there is convincing evidence that especially the presence of complement fixing antibodies against the subtypes M2, M4, and M8 is a reliable indicator for a more active course. Patients expressing only anti‐M9 (without anti‐M2) have biochemically all the typical features also found in classical anti‐M2 positive primary biliary cirrhosis patients, but seem not to advance to late stages. Since these antimitochondrial antibody‐subtypes are present even in very early stages without changing their pattern during the course, antimitochondrial antibody‐profiles can also be taken as early prognostic parameters. The evaluation of the immunological activity by antimitochondrial antibody‐subtype testing may further facilitate the decision whether therapy with ursodeoxycholic acid should be combined with steroids and/or immunosuppressive agents. The role of mitochondrial autoantigens in the induction of this chronic destructive bile duct process is also discussed. The concept is put forward that not bile ducts but naive(?) B‐cells expose the different mitochondrial antigens, thereby stimulating autoreactive T‐cells to provide a second signal for antibody production. The degree of breakage of tolerance to the different mitochondrial epitopes may be one crucial factor which determines the diversity of antimitochondrial antibody‐subtyp

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1995.tb00687.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:We have evaluated the link between haemostatic abnormalities and immune dysfunction in liver disease by evaluating parameters of cellular and humoral immunity in conjunction with coagulation profiles in rats following portacaval anastomosis, induction of portal hypertension by portal vein stenosis or by sham surgical procedures. Twelve weeks following surgery, portacaval shunted rats were markedly anaemic (8.9±0.6 g/dl; controls 12.3±1.4 g/dl, p>0.05), had low plasma fibrinogen levels (0.6±0.3 g/l, controls 2.5±0.2 g/l p>0.05) and markedly elevated fibrin(ogen) degradation products (FDP) titres (1/40–1/80; controls>1/10. p>0.05). Portal vein stenosed rats were less anaemic (11.5±0.8 g/dl), had near normal fibrinogen levels (2.1±0.3 g/l) but elevated FDP levels (1/40–1/80). Both portacaval shunted and portal vein stenosed rats had elevated serum IgG levels (35.1±14.1 g/l; 29.2±13.9 g/l respectively; control values 20±5.9 g/l p>0.05 for comparison with both experimental groups). Intrinsic lymphocyte proliferation to T and B cell mitogens was markedly depressed in the portacaval anastamosed rats when compared to controls. Serum factors inhibitory to control lymphocyte proliferation were noted in the shunted rats. Phagocytosis of complement and immunoglobulin sensitised sheep RBC by Kupffer cells purified from rats that had undergone portacaval shunting was markedly reduced (p>0.05). The increased degree of phagocytosis following exposure to LPS‐endotoxin (50 μg/ml) was proportionate in degree to the control group. Spontaneous release of bioactive lymphocyte activating factors (IL‐1 and IL‐6) by purified rat sinusoidal cell populations was decreased in the portacaval shunted group, and decreased still further following stimulation with LPS (50 μg/ml)in vitro.The observation that many of the haemostatic and immunological abnormalities associated with chronic liver disease are present in rats with surgically created portacaval shunts or with induced portal hypertension, lends credence to the hypothesis that shunting of portal blood is, at least in part, responsible for many of the systemic manifestations associated with c

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1995.tb00688.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:To clarify the relationship between hepatitis C virus infection and excessive alcohol intake, we carried out histological examination of the liver in 46 alcoholics with chronic hepatitis C virus infection and compared the findings in 55 patients with chronic hepatitis C, 38 with alcoholic liver disease, and 27 with chronic hepatitis B. The majority of alcoholics with chronic hepatitis C virus infection displayed virus‐related histological changes very similar to those in chronic hepatitis C, including frequent lymphoid follicles (34.7%) or aggregates (93.3%) in the portal tracts, mild necroinflammatory change (76.1%) in the parenchyma, and lymphocytosis in sinusoids (82.7%). Liver cell dysplasia and irregular regenerative activity of hepatocytes were rarely observed. The effects of alcohol on the liver were found to be minimal in the majority. These findings could suggest that the hepatic injury in the majority of alcoholics with chronic hepatitis C virus infection in Japan is due to persistent hepatitis C virus infection rather than to alcoholic injury. In addition, our study disclosed that the perivenular fibrosis which is designated as a histological characteristic of alcoholic liver disease is frequently observed in chronic hepatitis C. These similarities suggest that a similar fibrogenesis is present in chronic hepatitis C and alcoholic liver diseas

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1995.tb00689.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Granulomas in liver biopsy specimens from adult patients with chronic ductopenic cholestatic liver disease are a characteristic feature of primary biliary cirrhosis. However, we found a similar combination of abnormalities in 7 out of 100 native livers (7%) from patients who had orthotopic liver transplantation for primary sclerosing cholangitis. In a control group of native livers from 100 patients with primary biliary cirrhosis, the prevalence of granulomas was exactly the same, 7%. In the primary sclerosing cholangitis group, 13 additional livers showed a granulomatous epithelioid cell response, with or without foreign body type giant cells, to extravasated bile. All granulomas were noncaseating and non‐necrotizing; they consisted of epithelioid cells and often contained giant cells. Perigranulomatous lymphocytic infiltrates were generally mild to moderate. The granulomas involved portal tracts, scars, and hepatic parenchyma. Biopsy experience revealed that granulomas can be found in all stages of the disease. In contradistinction to the granulomas in primary biliary cirrhosis, the granulomas in primary sclerosing cholangitis did not represent granulomatous cholangitis – that is, they were not a feature of the duct destruction. The etiology of these lesions is not clear, but in some cases we found strong morphologic evidence that granulomas may form as a response to the leakage of bile or bile components. No evidence of infection or of sarcoidosis was found. Although adverse drug responses cannot be ruled out with certainty, review of the clinical histories made that mechanism unlikely. Thus, the presence of granulomas in chronic ductopenic cholestatic liver disease is not pathognomonic for primary biliary cirrhosis and, in rare instances (on average, in 3–4% of the biopsy samples), may be a feature of primary sclerosing cholan

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1995.tb00690.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Four subpopulations of hepatic macrophages, differing in size, were isolated from rat liver. The secretion of nitric oxide (NO), tumor necrosis factor‐α (TNF‐α), prostaglandin E (PGE) and interleukin‐1 (IL‐1) by freshly isolated as well as cultured cells was studied afterin vitrostimulation with the immunomodulator muramyl dipeptide (MDP) in free or liposome‐encapsulated form. Freshly isolated liver macrophages could be induced to secrete significant levels of NO, TNF‐α, PGE and IL‐1. The extent of secretion, however, varied substantially between macrophages of different size. The highest levels of secretion of TNF‐α, PGE and IL‐1 were observed in the fraction containing the large‐size macrophages, while progressively lower levels of secretion were observed with decreasing size. In constrast, the highest levels of NO secretion were observed by small macrophages and steadily decreased with increasing size. Hepatic macrophages of different size displayed differences in secretory potential duringin vitroculture. The ability of small liver macrophages to secrete NO, TNF‐α, or PGE, following activation with MDP, gradually increased with time in culture. In contrast, large liver macrophages gradually lost their secretory ability after 1–2 days and the intermedicate‐size cells after 2–3 days in culture. This functional heterogeneity in secretory properties among rat liver macrophages of different size is discussed with reference to their potential role and significance in host defense against meta

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1995.tb00691.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:A group of 24 patients underwent a 7–14‐day course of continuously infused Cyclosporin A (2 mg · kg‐1· day‐1) to treat a severe attack of ulcerative colitis. In 19 of them, including eight treated with total parenteral nutrition, we retrospectively analyzed the serum aminotransferase (AST/ALT) levels at the beginning and at the end of Cyclosporin infusion. The baseline levels of AST/ALT in the group were 19.9±3.2 and 31.4±6.4; on stopping Cyclosporin infusion, they were 43±15.8 and 119±56, respectively. Six patients showed an ALT change above 1.5 times the upper limit of reference. They included five of the eight patients treated with total parenteral nutrition (62.5%). In one of the six, ALT rose to 1000 U/l and was accompanied by full‐blown febrile cholangitis (proven by liver biopsy). This episode was preceded by excessive accumulation of Cyclosporin in blood. The development of liver toxicity was independent of the length of Cyclosporin treatment, nor did it impair drug efficacy. Thus, in these patients total parenteral nutrition and Cyclosporin were synergistic, causing twice the frequency of liver damage (62.5%) reported for ulcerative colitis patients on total parenteral nutrition alone (37%). Total parenteral nutrition should not be used to support patients needing Cyclosporin for autoimmune disease. However, too high a dose of Cyclosporin may cause live

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1995.tb00692.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:An increase in serum laminin levels has been reported in patients with liver disease; however, the mechanisms for this increase have not yet been clarified. In the present study, the laminin content of liver biopsy specimens obtained from patients with alcoholic liver disease and nonalcoholic liver disease was determined with a one‐step sandwich enzymeimmunoassay system, using monoclonal antibodies for human placental laminin. Hepatic laminin content was significantly higher in patients with liver disease than in normal controls. In alcoholic liver disease, the content in patients with mild fibrosis was lower than in patients with advanced types of alcoholic liver disease. In non‐alcoholic liver disease, the hepatic laminin content tended to increase in parallel with the progression of fibrosis. The laminin content in alcoholic liver disease was significantly higher than in the corresponding type of non‐alcoholic liver disease. Hepatic total collagen content increased in parallel with the progression of fibrosis in both alcoholic liver disease and non‐alcoholic liver disease. The ratio of laminin to total collagen content was highest in alcoholic liver disease showing mild fibrosis and decreased in parallel with the progression of fibrosis. In contrast, the ratio was low in all types of nonalcoholic liver disease. The ratio in patients with alcoholic liver disease was significantly higher than in those with the corresponding non‐alcoholic liver disease. Hepatic laminin content increased in parallel with the increase in hepatic type IV collagen in alcoholic liver disease, and the correlation was statistically significant. However, a similar correlation was not found in non‐alcoholic liver disease. These results indicate that the response of laminin synthesis to alcoholic liver disease is strong in mild fibrosis and reached a plateau at a relatively early stage of fibrosis. The stimulation for laminin synthesis in non‐alcoholic liver disease is different from that in alcoholic

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1995.tb00693.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:An unusual case of systemic amyloidosis complicated by portal hypertension is reported. In this condition, portal hypertension is a rare event associated with poor prognosis. In our patient, severe presymptomatic sinusoidal portal hypertension was demonstrated by hepatic vein catheterization and coincided with abundant perisinusoidal amyloid infiltration. Despite these features and the absence of objective response to 20 courses of melphalan and prednisone, the patient was still in good clinical condition 4 years after initial diagnosis. This observation suggests that in primary amyloidosis, the incidence of sinusoidal portal hypertension might be underestimated and also that it may be associated with a relatively good prognosis.

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1995.tb00694.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Book reviewed in this article:Hall, Pauline, ed.Alcoholic liver disease: pathology and pathogenesis.Arias IM, Boyer JL, Fausto N, Jacoby WB, Schachter D, Shafritz DA, eds.The liver: biology and pathobiologyBlaser MJ, Smith PD, Ravdin JI, Greenberg HB, Guerrant RL, eds. ISBN 0–7817–0226–7.Infections of the gastrointestinal

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1995.tb00695.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY