摘要:

AbstractImmune complexes may be important in the pathogenesis of the liver disease associated with idiopathic ulcerative colitis. In the present study, we documented Fc receptor‐mediated clearance by the reticuloendothelial system of immune complex‐like material from the systemic circulation of 25 healthy control subjects, 19 patients with ulcerative colitis alone, 9 patients with ulcerative colitis and elevated liver enzyme tests and 8 patients with various other formsof chronic liver disease. Following an intravenous infusion of IgG‐tagged51Cr‐labeled autologous erythrocytes, serial blood samples were drawn over a 2‐hr period of time, and computer‐generated clearance curves were obtained. The time required for clearance of 50% of infused erythrocytes (T1/2) was then calculated. Serum immunoglobulin (IgA, IgG and IgM), complement (C3 and C4) and immune complex‐like activity (IgG and IgM types) were also determined. Sixteen of 19 (84%) ulcerative colitis patients and 7 of 8 (88%) chronic liver disease patients had normal clearance T1/2's (when compared to 25 healthy controls). Conversely, only 1 of 9 (11%) ulcerative colitis + chronic liver disease patients demonstrated normal clearance function. Aside from serum IgM levels, the results of serum immunoglobulin, complement and immune complex‐like determinations were similar in ulcerative colitis and ulcerative colitis + chronic liver disease patients. Serum IgM levels, however, were significantly decreased in ulcerative colitis patients and increased in ulcerative colitis + chronic liver disease patients (p<0.001).These results indicate that the reticuloendothelial system of patients with ulcerative colitis and chronic liver disease is impaired in its ability to clear immune complex‐like material from the systemic circulation. This finding tendsto support the hypothesis that immune complexes are of pathogenic importance in the liver disease associated with idiopathic u

ISSN:0270-9139    

DOI:10.1002/hep.1840060102

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractTo determine the feasibility of liver biopsy immunotyping to characterize hepatic lymphoid malignancies, we employed a panel of monoclonal antibodies on snapfrozen hepatic tissue from 18 patients. Six patients proved to have a histologic diagnosis of lymphoid malignancy. By using free avidin and biotin‐blocking reagents to block endogenous biotin, followed by standard immunochemistry, immunotyping was successful in all six cases. Serial section typing allowed delineation of complex B cell phenotypes. Furthermore, architecture was preserved allowing discernment of disease patterns (e.g.), sinusoidal, hairy cell leukemia vs. portal, follicular small‐cleaved cell lymphoma. Unexpectedly, we found striking expression of common ALL antigen in normal bile canaliculi, which may prove of diagnostic or therapeutic relevance. This study establishes the utility of immunohistochemical techniques applied to hepatic biopsies as a valuable adjunct to histologic diagnosis as well as a tool in revealing the immunobiology of the li

ISSN:0270-9139    

DOI:10.1002/hep.1840060103

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractThe binding activity of polymerized human serum albumin was determined in 202 HBsAg carriers. The presence of polymerized human serum albumin receptor sites was tested by hemagglutination and differentiated from antihuman albumin antibodies by immunofluorescence, isolation of IgG and IgM fractions and testing of HBsAg anti‐HBs immune complexes. A granular pattern with anti‐HBs was specific for polymerized human serum albumin receptor sites as demonstrated with purified HBsAg. In addition, a linear pattern with fluoresceinated antihuman immunoglobulins might suggest the presence ofantihuman albumin antibodies (which was generally due to an IgG antibody). However, a granular pattern with fluoresceinated antihuman immunoglobulins may indicate the presence of HBsAg anti‐HBs immune complexes. A weak linear pattern was also observed simultaneously in these cases, probably due to IgM antihuman albumin antibodies or an antipolymerized human serum albumin receptor site antibody.Of 202 HBsAg‐positive patients, 71 showed polymerized human serum albumin receptor sites activity. The highest percentage of polymerized human serum albumin receptor sites was found among patients showing HBeAg and hepatitis B virus DNA polymerase positivity (96%), followed by HBeAg positivity and hepatitis B virus DNA polymerase negativity (48%), and anti‐HBe positivity and hepatitis B virus DNA polymerase negativity (17%). In addition, a significant correlation between polymerized human serum albumin titers and hepatitis B virus DNA polymerase was found (r = 0.573, p<0.01). However, at a similar HBeAg titer, patients who were positive for hepatitis B virus DNA polymerase had a higher polymerized human serum albumin receptor sites titer than those who were negative for hepatitis B virus DNA polymerase.The presence of a granular pattern with anti‐HBs or fluoresceinated antihuman immunoglobulins means a positivity to polymerized human serum albumin receptor sites or the presence of HBsAg anti‐HBs immune complexes, respectively. Furthermore, polymerized human serum albumin receptor sites titers correlate with hepatitis B virus DNA polymerase concentrations and may serve as indicators of vira

ISSN:0270-9139    

DOI:10.1002/hep.1840060104

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

Abstractβ2−Microglobulin display was examined in 131 liver biopsies from patients with acute and chronic type B hepatitis, using an indirect immunoperoxidase method. Enhanced expression of β2−microglobulin on hepatocyte membranes was observed in patients with acute hepatitis, chronic active hepatitis with moderate to severe activity and cirrhosis, when compared with normal liver. In acute hepatitis, β2−microglobulin‐positive hepatocytes were mainly observed in perivenular areas in association with bridging necrosis. In chronic hepatitis, β2−microglobulin‐positive hepatocytes were observed mainly in periportal zones and in some areas of lobular activty.Diffuse‐enhanced display of β2−microglobulin on hepatocytes was observed in 5 of 6 patients treated with lymphoblastoid interferon as part of a trial of antiviral therapy. The mechanism by which β2−microglobulin display is enhanced on hepatocytes in patients not treated with interferon is uncertain. However, display of β2−microglobulin on hepatocytes probably reflects display of HLA‐A, B and C antigens and may influence the course of hepatitis B virus infection by increasing susceptibility of the affectedcells to T

ISSN:0270-9139    

DOI:10.1002/hep.1840060105

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractThe role of the measurement of hepatic iron in the diagnosis of genetic hemochromatosis was studied, with particular reference to the differentiation of early hemochromatosis from alcoholic siderosis and the critical hepatic iron concentration associated with fibrosis in hemochromatosis. Hepatic iron was measured in 30 homozygous relatives of 17 hemochromatosis probands, 8 heterozygous relatives, 51 patients with alcoholic liver disease and 40 control subjects. Hepatic iron concentrations were greatly increased in the majority of homozygous hemochromatosis subjects, and there was little overlapwith the other groups. In the absence of alcoholism, fibrosis or cirrhosis in hemochromatosis was present only with hepatic iron concentrations above a threshold of approximately 400 μmoles per gm (22.3 mg per gm) dry weight. In some heterozygous hemochromatosis subjects and in some alcoholic patients, hepatic iron concentrations were in the range seen in young homozygous subjects. However, an age‐related rise in hepatic iron was seen only in hemochromatosis homozygotes, and calculation of an hepatic iron index (hepatic iron/age) resulted in a clear distinction between homozygotes and the other three groups. It is concluded: (a) that chemical measurement of hepatic iron concentration, when corrected for the age of the subject, reliably distinguishes early hemochromatosis from alcoholic siderosis, and (b), that there appears to be a threshold level of hepatic iron above which there is a high risk of fibros

ISSN:0270-9139    

DOI:10.1002/hep.1840060106

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractFerritin‐like particles were observed in bile canaliculi of patients with iron overload. These particles have been further investigated by: (1) a staining method enhancing the size and contrast of ferritin protein, and (2) electronprobe microanalysis detecting the presence of the elements iron and phosphorus.Morphological observation of coated vesicles in the cytoplasm adjacent to the bile canaliculi and coated pits in the canalicular membrane suggests a transport mechanism via membrane‐bound organelles.Support is given to the theory that part of the iron, stored in the liver, leaves the hepatocyte by excretion of ferritininto the b

ISSN:0270-9139    

DOI:10.1002/hep.1840060107

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractCCl4is proposed to induce cellular injury through its metabolites that are generated by a cytochrome P‐450 dependent step. These free radical products can interact with membrane structures, thereby generating lipid peroxides. The latter process has been implicated as a major mechanism of CCl4hepatoxicity, although this relationship has been difficult to demonstrate when using isolated hepatocyte preparations. This report demonstrates that there are at least two mechanisms by which CCl4induces injury in isolated hepatocytes. One occurs within minutes of exposure to CCl4and is characterized by modest malondialdehyde formation and no decline in cellular‐reduced glutathione. SKF 525A, metyrapone and promethazine did not protect against this early damage. A second phase of damage, evident particularly after 3 hr, is characterized by a marked increase in malondialdehyde formation, a fall in cellular glutathione and substantial further cellular damage. These changes could be moderated by the cytochrome P‐450 inhibitors and promethazine, and antioxidant. Further examination of the initial phase of damage reveals an immediate dose‐related inhibition of O2consumption. This could not be prevented by SKF 525A or metyrapone and was associatedwith loss of ability to stimulate mitochondrial respiration with dinitrophenol. Rapid recovery to initial O2consumption rates occurred with time as CCl4evaporated from the incubation system. This was associated with a partial return of dinitrophenol stimulation of mitochondrial O2consumption despite significant glutamate dehydrogenase release. A portion of this recovery could be inhibited by SKF 525A, suggesting that some O2consumption was due to CCl4metabolism and ensuing lipid peroxidation. These data suggest that early CCl4toxicity is adirect consequence of its solvent properties and is partially reversible; subsequent damage may be mediated by lipid peroxidation. This solvent injury has not been previously recognized and may have relevance not only to a reversible toxicityas demonstrated with isolated hepatocytes but alsoin vivo

ISSN:0270-9139    

DOI:10.1002/hep.1840060108

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractSevere liver disease may be associated with a reduction in plasma concentration of high density lipoprotein and an impairment of plasma cholesterol esterification. These changes were confirmed in two patients with severe acute on chronic alcoholic liver disease. In five additional patients with biopsy‐proven clinically compensated cirrhosis, there wasminimal reduction in concentration of plasma cholesteryl esters; there was, however a reduction of the plasma high density lipoprotein concentration to only 48 to 66% of normal. The particle size distribution of high density lipoprotein in these five patients was determined by gradient gel electrophoresis. The high density lipoprotein2subfraction was preserved. The high density lipoprotein3subfraction, however, was markedly changed with a reduction in the normal particles of radius 4.3 m and an accentuation of smaller particles of radius 3.9 m; in two patients, these smaller particles were the major high density lipoprotein subpopulation. Further investigations of this finding of a distinctive distribution of high density lipoprotein subpopulations in patient with chronic liver disease may provide new insights into high density lipoprotein metabolis

ISSN:0270-9139    

DOI:10.1002/hep.1840060109

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractThe value of serum bile acid concentrations for predicting prognosis in cirrhotics was compared with the prognostic significance of clinical and laboratory findings in a prospective 1‐year study of 76 patients with cirrhosis. A commercial radioimmunoassay for total serum‐conjugated primary bile acids was used. Of 76 patients, 16 died within the follow‐up period. The concentration of bile acids in serum more closely correlated with mortality in cirrhosis than the commonly used clinical and laboratory parameters such as the Number Connection Test, ascites, albumin, pseudocholinesterase, bilirubin, prothrombin time and nutritional state. Serum bile acids alone yielded a prediction of mortality comparable to the Child classification. When logistic regression analysis was performed, optimal prediction of prognosis was achieved with the combination of serum bile acids and the Number Connection Test. Serum bile acid levels alone or in combination with the Number Connection Test may be a clinically useful prognostic index in cirr

ISSN:0270-9139    

DOI:10.1002/hep.1840060110

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractTransmission and scanning electron microscopy were utilized to follow the degeneration of bile ducts of lampreys (Petromyzon marinusL.) during metamorphosis. The convoluted bile ducts of larval lampreys are surrounded by rich sinusoids, but this intimate biliovascular relationship is lost during metamorphosis because the bile duct degeneration is accompanied by the development of thick periductal fibrosis. Lipocytes, which are present not only in the parenchyma but also in the interstitial tissue of the liver, increase in number in the periductal fibrous tissue, and their processes are directly opposed to collagen fibrils. Fibrillar materials in the dilated cisternae of the rough endoplasmic reticulum andthe nuclear envelope of lipocytes are believed to be excreted by exocytosis in a manner similar to such excretion by fibroblasts. The findings suggest that lipocytes are responsible for the periductal fibrosis during biliary atresia in lampreys. This animal might prove to be an interesting model in which to study the biology and fibrogenic potential of lipocytes.

ISSN:0270-9139    

DOI:10.1002/hep.1840060111

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY