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1. |
A Mitochondrial Antigen‐Antibody System in Cholestatic Liver Disease Detected by Radioimmunoassay |
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Hepatology,
Volume 2,
Issue 1,
1982,
Page 1-7
Michael Manns,
Karl‐Hermann Meyer,
Zum Büschenfelde,
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摘要:
AbstractA radioimmunoassay (RIA) was established for the detection of antimitochondrial autoantibodies (AMAs) in patient sera. AMAs were detected by RIA in 12 of 14 patients with primary biliary cirrhosis and in 3 of 29 patients with chronic active hepatitis. AMAs were detected by indirect immunofluorescence in all sera positive by RIA. In addition, two patients with primary biliary cirrhosis and one patient with chronic active hepatitis were AMA positive when tested by indirect immunofluorescence, but negative when tested by RIA. AMAs were not detected by RIA or indirect immunofluorescence in 121 further patients with various hepatic and nonhepatic diseases, including healthy controls. The RIA detects an AMA directed against one determinant of a mitochondrial antigen which bears the characteristics of the previously described primary biliary cirrhosis antigen (M2 antigen). The RIA described is a sensitive and specific test for the detection of one mitochondrial autoantibody associated with chronic cholestatic liver diseases displaying the morphology of primary biliary cirrhosis in chronic active hepatitis or liver biopsy specimens. Antibodies against other mitochondrial antigens do not react in this assay system.
ISSN:0270-9139
DOI:10.1002/hep.1840020102
出版商:W.B. Saunders
年代:1982
数据来源: WILEY
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2. |
Toxic Doses of Acetaminophen Suppress Hepatic Glutathione Synthesis in Rats |
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Hepatology,
Volume 2,
Issue 1,
1982,
Page 8-12
Bernhard H. Lauterburg,
Jerry R. Mitchell,
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摘要:
AbstractThe effect of a toxic dose of acetaminophen on hepatic glutathione turnover was studied in fed and fasted rats. Following the administration of 1 gm per kg of acetaminophen, the fractional rate of glutathione turnover increased from 0.19 to 0.28 hr−1in fed rats and from 0.43 to 0.50 hr−1in rats fasted for 48 hr. The increase in the fractional rate of turnover was proportionally much less than the decrease in hepatic glutathione concentration resulting from the toxic dose of acetaminophen. Thus, the estimated hepatic synthesis of glutathione decreased from 0.86 and 1.50 μmole per gm liver hr to 0.59 and 0.53 μmole per gm hr in fed and fasted rats, respectively. The excretion of acetaminophen‐sulfate was significantly decreased in fasted rats. The fraction of administered acetaminophen metabolized to the mercapturic acid, however, was similar in both groups. Nevertheless, all fasted animals had massive centrilobular necrosis whereas virtually no necrosis was observed in fed animals. The administration of sulfate did not protect against liver injury in fasted rats. In view of the similar synthesis of glutathione in fed and fasted rats following a toxic dose of acetaminophen, an inability to synthesize adequate quantities of glutathione or a decreased availability of sulfate cannot account for the increased susceptibility to liver injury in the fasted state. However, a toxic dose of acetaminophen depletes the hepatic glutathione to a lower nadir before glutathione is repleted by synthesis, and a greater amount of tissue arylation occurs during this brief period of critically depleted glut
ISSN:0270-9139
DOI:10.1002/hep.1840020103
出版商:W.B. Saunders
年代:1982
数据来源: WILEY
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3. |
Collagen Production by Rat Hepatocytes and Sinusoidal Cells in Primary Monolayer Culture |
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Hepatology,
Volume 2,
Issue 1,
1982,
Page 13-18
Scheffer C. G. Tseng,
Philip C. Lee,
Peter F. Ells,
D. Montgomery Bissell,
Edward A. Smuckler,
Robert Stern,
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摘要:
AbstractThe cellular sources of collagen in normal rat liver have been examined. Hepatocytes and nonparenchymal (sinusoidal) cells were isolated and established in primary monolayer culture. These cells were incubated with radiolabeled proline in the presence of L‐ascorbate and β‐amino‐propionitrile. Nondialyzable material was prepared from the cell layer and the medium from each type of culture. The level of collagen accumulation was determined by measuring labeled hydroxyproline and sensitivity to purified bacterial collagenase. In hepatocytes, collagen represented 0.2% of both secreted and cell‐associated labeled protein. In sinusoidal cells, collagen was 3.2% of secreted and 1.1% of cell‐associated proteins. The total secreted labeled collagen, expressed per microgram of DNA, was similar in hepatocytes and sinusoidal cells. However cell‐associated collagen in hepatocyte culture was approximately 10‐fold that present in sinusoidal cells. These findings indicate that, while collagen formation is a relatively important function of sinusoidal cells, in normal liver the contribution of hepatocytes to total hepatic collagen accumulation may
ISSN:0270-9139
DOI:10.1002/hep.1840020104
出版商:W.B. Saunders
年代:1982
数据来源: WILEY
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4. |
Nonparenchymal Cells Cultivated from Explants of Fibrotic Liver Resemble Endothelial and Smooth Muscle Cells from Blood Vessel Walls |
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Hepatology,
Volume 2,
Issue 1,
1982,
Page 19-28
Bruno Voss,
Jürgen Rauterberg,
Gerhard Pott,
Ute Brehmer,
Salah Allam,
Rolf Lehmann,
Dirk B. V. Bassewitz,
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摘要:
AbstractTissue specimens from human fibrotic liver obtained by needle biopsy were cultured. Two cell types emerged from the tissue explants. From their morphology and biosynthetic products they resembled smooth muscle cells and endothelial cells from blood vessel walls. In the “endothelial” cells, factor VIII‐associated protein was demonstrated by indirect immunofluorescence. Synthesis of collagen types I and III, basement membrane collagen types IV and V, and fibronectin by both cell types was observed by immunofluorescence microscopy. Homogeneous cultures of “smooth muscle cells” were observed in subcultures. After incubation with [14C]glycine, collagen was isolated and characterized by CM cellulose chromatography, and consisted mainly of types I and III. These data suggest involvement of mesenchymal cells in hepatic fibrosis; they presumably originate from blood vessel or sinusoi
ISSN:0270-9139
DOI:10.1002/hep.1840020105
出版商:W.B. Saunders
年代:1982
数据来源: WILEY
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5. |
Morphologic Study of Intermediate Filaments in Rat Hepatocytes |
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Hepatology,
Volume 2,
Issue 1,
1982,
Page 29-38
Samuel W. French,
Isao Kondo,
Tetsuya Irie,
Thomas J. Ihrig,
Nancy Benson,
Robert Munn,
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摘要:
AbstractRat livers perfused with 0.5% Triton X‐100 for 15 to 90 min followed by 1% sodium dodecyl sulfate for 30 min were studied by electron microscopy and polyaerylamide gel electrophoresis. After 15 min of perfusion, a rich network of intermediate filaments and microtubules was visualized in the cytoplasm of hepatocytes. Using stereopairs, branching was visualized. Connections of filaments were noted with nuclei, centrioles, microtubules, vesicles, and rough endoplasmic reticulum. The existence of connections supported the concept that intermediate filaments may function to integrate mechanically the cytoplasmic space as postulated by Lazaride
ISSN:0270-9139
DOI:10.1002/hep.1840020106
出版商:W.B. Saunders
年代:1982
数据来源: WILEY
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6. |
Antiviral Treatment of Chronic Hepatitis B Virus Infection: Infectious Virus Cannot Be Detected in Patient Serum after Permanent Responses to Treatment |
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Hepatology,
Volume 2,
Issue 1,
1982,
Page 39-49
George H. Scullard,
Harry B. Greenberg,
Joseph L. Smith,
Peter B. Gregory,
Thomas C. Merigan,
William S. Robinson,
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摘要:
AbstractFourteen chimpanzees were inoculated with pre‐ and posttreatment sera from seven patients with persistent hepatitis B virus infection and chronic hepatitis who had permanent responses of their infection to treatment with interferon and/or adenine arabinoside. Inoculation of pretreatment serum at a dilution of 10−8from a patient with a Type I response to treatment [disappearance of Dane particle DNA polymerase (DNAP) activity, HBeAg, and HBsAg from serum] resulted in infection, while undiluted posttreatment serum (all markers negative) failed to infect another animal. Pretreatment sera (DNAP, HBeAg, and HBsAg positive) from all of six patients with a Type II response to treatment (disappearance of DNAP activity and HBeAg but not HBsAg from serum) led to infection in six chimpanzees after inoculation of serum dilutions varying between 10−2and 10−7. Inoculation of undiluted posttreatment sera (HBsAg positive and DNAP and HBeAg negative) from the same six patients produced no evidence of hepatitis B virus infection in another six animals. These results indicate that a Type I or II response to treatment with these antiviral agents reduces the infectivity in the serum of patients with chronic hepatitis B to below the level of detection by this assay. Such changes should be useful in interrupting spread of the infection between individuals. Our findings suggest that the serum of some patients who, without treatment are HBsAg positive and DNAP and HBeAg negative, may also be free of detectable infectious hepatitis
ISSN:0270-9139
DOI:10.1002/hep.1840020107
出版商:W.B. Saunders
年代:1982
数据来源: WILEY
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7. |
Acute Type B Hepatitis among HBsAg Negative Patients Detected by Anti‐HBc IgM |
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Hepatology,
Volume 2,
Issue 1,
1982,
Page 50-53
Peter Kryger,
Jan Aldershvile,
Lars R. Mathiesen,
Jens O. Nielsen,
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摘要:
AbstractA consecutive group of 169 patients with acute hepatitis found negative for hepatitis B surface antigen (HBsAg) and negative for IgM antibody against hepatitis A (anti‐HAV IgM) was studied for presence of IgM antibody against hepatitis B core antigen (anti‐HBc IgM) by ELISA. Anti‐HBc IgM was found in a total of 34 of 60 patients with detectable total anti‐HBc. One hundred and nine patients had no detectable anti‐HBc IgM and no total anti‐HBc and were thus considered as having acute non‐A, non‐B hepatitis. Among the 34 patients with anti‐HBc IgM in their first serum sample, 23 were anti‐HBs negative and all had high and steadily decreasing ratio unit (RU) values for anti‐HBc IgM (mean RU value 17.1). Twelve of the 23 patients showed seroconversion to anti‐HBs during the follow‐up, indicating an actual hepatitis B virus infection. Eleven of the 34 anti‐HBc IgM positive patients had anti‐HBs in their first serum sample. In this group, the RU values for anti‐HBc IgM were high and steadily declining and the initial values were significantly lower (mean RU value 9.9) (p<0.05) than in the anti‐HBs negative group. Evidence is provided that anti‐HBc IgM in serum from patients with HBsAg negative hepatitis with or without anti‐HBs indicates an actual hepatitis B virus infection.According to generally accepted criteria, the demonstration of anti‐HBc IgM identified 20% of the 169 patients with acute non‐A, non‐B hepatiti
ISSN:0270-9139
DOI:10.1002/hep.1840020108
出版商:W.B. Saunders
年代:1982
数据来源: WILEY
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8. |
A Comparison of Acute Reversible Pre‐ and Postsinusoidal Portal Hypertension on Salt and Water Retention in the Dog |
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Hepatology,
Volume 2,
Issue 1,
1982,
Page 54-58
Vernon Campbell,
Paul D. Greig,
Jeff Cranford,
Bernard Langer,
Melvin Silverman,
Laurence M. Blendis,
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摘要:
AbstractTo define the relationship between portal hypertension and renal excretion of salt and water, two acute animal models of portal hypertension were investigated. In both models, it was necessary for systemic and renal hemodynamics to remain unchanged during the creation of portal hypertension so as to eliminate the effects of change in these parameters on renal excretion.In eight dogs, portal hypertension was induced by controlled tightening of a ligature around the superior hepatic vein and changes in hemodynamics were prevented by controlled i.v. titration with canine plasma. Rises in portal pressure 9.3 ± 2.6 to 15.6 ± 2.3 cm H2O were associated with significant decreases in urine volume 1.57 ± 0.53 to 0.66 ± 0.21 ml per min (p<0.05) and urinary sodium excretion [340 ± 82 to 145 ±75 mEq per min (p<0.05)]. In contrast, similar experiments in five dogs in which the portal vein was partially ligated with increases in portal pressure from 8.3 ± 0.6 to 18.6 ± 0.5 cm H2O resulted in no change in urinary volume or sodium excretion.Acute reversible portal hypertension induced by hepatic vein constriction is associated with acute reversible retention of water and salt in the absence of changes in renal blood flow and creatinine clearance which only occur when the liver is involved and not with portal vein const
ISSN:0270-9139
DOI:10.1002/hep.1840020109
出版商:W.B. Saunders
年代:1982
数据来源: WILEY
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9. |
Bile Acid Metabolism in Cirrhosis. VIII. Quantitative Evaluation of Bile Acid Synthesis From [7β‐3H]7α‐Hydroxycholesterol and [G‐3H]26‐Hydroxycholesterol |
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Hepatology,
Volume 2,
Issue 1,
1982,
Page 59-66
Marc Goldman,
Z. Reno Vlahcevic,
Charles C. Schwartz,
Jan Gustafsson,
Leon Swell,
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摘要:
AbstractIn order to evaluate more definitively the observed aberrations in the synthesis of cholic and chenodeoxycholic acids in patients with advanced cirrhosis, two bile acid biosynthesis pathways were examined by determining the efficiency of conversion of [3H]7α‐hydroxycholesterol and [3H] 26‐hydroxycholesterol to primary bile acids. Bile acid kinetics were determined by administration of [14C]cholic and [14C]chenodeoxycholic acids. Cholic acid synthesis in cirrhotic patients was markedly depressed (170 vs. 927 μmoles per day) while chenodeoxycholic acid synthesis was reduced to a much lesser degree (227 vs. 550 μmoles per day). The administration of [3H]7α‐hydroxycholes‐terol allowed for an evaluation of the major pathway of bile acid synthesis via the 7α‐hydroxylation of cholesterol. This compound was efficiently incorporated into primary bile acids by the two normal subjects (88 and 100%) and two cirrhotic patients (77 and 91%). However, the recovery of the label in cholic acid was slightly less in cirrhotic patients than in normal subjects. [3H]26‐hydroxycholesterol was administered to ascertain the contribution of the 26‐hydroxylation pathway to bile acid synthesis. All study subjects showed poor conversion (9 to 22%) of this intermediate into bile acids.The results of this study suggest that a major block in the bile acid synthesis pathway in cirrhosis is at the level of 7α‐hydroxylation of cholesterol (impairment of 7α‐hydroxylase) and/or in the feedback triggering mechanism regulating bile acid synthesis. The data also suggest that the 26‐hydroxylation pathway in normal subjects and patients with cirrhosis is a minor contributor to synthesis of the primary bile acids. Therefore, the relative sparing of chenodeoxycholic acid synthesis observed in cirrhotic patients is not due to preferential synthesis of this bile acid via th
ISSN:0270-9139
DOI:10.1002/hep.1840020110
出版商:W.B. Saunders
年代:1982
数据来源: WILEY
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10. |
The Effect of Portal Diversion on the Early Stages of Liver Carcinogenesis in the Rat |
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Hepatology,
Volume 2,
Issue 1,
1982,
Page 67-71
Lorne E. Rotstein,
Leonard Makowka,
George Lee,
Emmanuel Farber,
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摘要:
AbstractThe effect of portal diversion by ameroid constriction was studied in the carcinogenic process in the rat after initiation of foci by diethylnitrosamine and after the establishment of putative preneoplastic nodules. Portal diversion or portal diversion plus partial hepatectomy did not act to promote or select for the development of nodules. Furthermore, portal diversion did not alter the natural history of established nodules. These results suggest that vascular factors are not important at these early stages of the carcinogenic process in the rat liver.
ISSN:0270-9139
DOI:10.1002/hep.1840020111
出版商:W.B. Saunders
年代:1982
数据来源: WILEY
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