Antibody to superoxide dismutase, autoimmune hepatitis, and antibody tests for hepatitis C virus.
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Autoantibodies↗
Biomedical subjects
G Toda
Publications and source records attributed to G Toda.
Hepatocyte plasma membrane glycosphingolipid reactive with sera from patients with autoimmune chronic active hepatitis: its identification as sulfatide.
Sera from patients with autoimmune chronic active hepatitis were found to contain IgG-class antibody to the acidic glycosphingolipid fraction from rabbit hepatocyte plasma membrane by solid-phase enzyme-linked immunosorbent assay. Using serum positive for the antibody as a probe, we isolated the target antigen by Iatrobeads column chromatography. Analysis by thin-layer chromatography and negative ion fast atom-bombardment mass spectrometry revealed that the antigen was sulfatide. The presence of antisulfatide antibody was also confirmed by immunoblotting. The reactivity of the serum with sulfatide was diminished by preincubation of the serum with galactosylceramide-6-sulfate and sulfatide, indicating that the antibody reacted with sulfated galactosylceramide regardless of the position of the sulfate residue. The antibody was found in 92.3%, 42.9%, 15.8%, 14.2%, 0% and 0%, respectively, of patients with autoimmune chronic active hepatitis, primary biliary cirrhosis, cirrhosis, systemic lupus erythematosus, chronic active hepatitis and chronic persistent hepatitis. Thus antisulfatide antibody was characteristic of autoimmune-type chronic liver diseases. Antisulfatide antibody was absorbed by rabbit hepatocyte plasma membrane. Preincubation of sera with sulfatide immobilized on Sepharose decreased their reactivities with not only sulfatide but also rabbit plasma membrane and rat hepatocytes. Therefore sulfatide may be a target antigen of the antibody to hepatocyte surface membrane.
Antigens, Surface↗
A multi-center double-blind controlled trial of ursodeoxycholic acid for primary biliary cirrhosis.
A multi-center double-blind controlled trial of ursodeoxycholic acid (UDCA) for treatment of primary biliary cirrhosis (PBC) was carried out. Twenty two and 23 patients were treated with 600 mg/day UDCA and placebo, respectively, for 24 weeks. In UDCA-treated patients, fall of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma-glutamyltranspeptidase activities started within 4 weeks after start of the trial and continued throughout the trial period. The serum IgM level fell in 7 UDCA-treated patients examined but not in 10 placebo-treated patients examined. Serum bilirubin concentration showed no significant change at the end of the study in either of UDCA- and placebo-treated group of patients. There was no significant difference between these two groups with respect to the frequency of improvement of pruritus. In UDCA-treated patients, serum bile acid composition changed markedly, though its concentration showed no significant change. The percentage of total bile acid which ursodeoxycholic acid took up increased, whereas those which cholic acid, chenodeoxycholic acid and deoxycholic acid took up were decreased.
Alanine Transaminase↗
Serum immunoreactive prolyl 4-hydroxylase as a specific marker of hepatocellular necrosis.
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Clinical Enzyme Tests↗
[Evaluation of plasma tissue plasminogen activator (I-PA) levels in patients with liver diseases].
Previous studies have demonstrated that plasma tissue plasminogen activator (t-PA) level was elevated in patients with liver disease. In this study, t-PA antigen levels were investigated in patients with acute hepatitis (AH; N = 12), chronic hepatitis (CH; N = 8), compensated liver cirrhosis (CLC; N = 40), decompensated liver cirrhosis (DLC; N = 23) and hepatocellular carcinoma (HCC; N = 35). The increased t-PA levels (higher than 14 ng/ml) were found in 33% (4/12) of AH on the early hospital days, 25% (2/8) of CH, 45% (18/40) of CLC and 91% (21/23) of DLC, and 60% (21/35) of Hcc cases. In patient with LC, the correlations between t-PA levels and serum total bilirubin (T.Bill) and hepatic synthetic functions were investigated. The results were that the t-PA levels correlated positively with T. Bil and negatively with liver synthetic functions such as albumin, protein C and choline-esterase, indicating that t-PA increased almost in proportion to the deterioration of hepatic function. Serial determination of t-PA in patients with HCC treated by transcatheter arterial embolization (TAE) revealed that TAE failed to normalize the t-PA levels. In one case of HCC complicated with disseminated intravascular coagulation (DIC), t-PA showed a marked increase at acute phase of DIC and subsequent decrease after the successful treatment for DIC by gabexate mesilate (FOY) infusion. These results suggest that increased t-PA in liver disease is due mainly to deterioration of hepatic function, and that secondary fibrinolytic state, such as DIC, is also a contributing factor.
Adult↗
Heterogeneity in lectin-binding characteristics of human lymphokine-activated killer cells.
The binding of various lectins to human lymphokine-activated killer (LAK) cells was investigated. Human peripheral blood lymphocytes were cultured for 3 days with recombinant interleukin-2 (rIL-2), and then stained with 20 kinds of lectins. There were four types of lectin-binding patterns: (a) negative staining; (b) weakly positive staining; (c) strongly positive staining; and (d) two populations, one weakly and one strongly positive staining. Among the 20 kinds of lectins, both Lens culinaris agglutinin (LCA) and Pisum sativum agglutinin (PSA) showed two peaks in the staining patterns on LAK cells (type 4). We separated these two populations of LAK cells by using a cell sorter, and assayed them for cytotoxic activity against 51Cr-labeled Hela cells. The LAK cells that were strongly stained by LCA or PSA [LCA (or PSA)-bright LAK cells] showed stronger cytotoxic activity than the LAK cells that were weakly stained by LCA or PSA [LCA (or PSA)-dull LAK cells]. Furthermore, we separated lymphocytes with LCA or PSA before culturing them with rIL-2 (LAK precursor), and we found that both LCA-bright and PSA-bright lymphocytes can develop into LAK cells with higher cytolytic activity. LCA-bright lymphocytes kept their ability to be stained strongly with LCA even after culture with rIL-2 for 3 days. Similarly, LCA-dull lymphocytes were still stained weakly after culture with rIL-2. Two-color assay of LAK cells revealed that 78% of NK (CD16+)-LAK cells and 46% of T (CD3+)-LAK cells were LCA-bright cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Antigens, CD↗
Significant increase in the antibody to Gal alpha 1-3Gal structure in sera of patients with hepatocellular carcinoma after transcatheter arterial embolization.
Sera from the patients with chronic liver diseases and hepatocellular carcinoma (HCC) were tested for reactivity with neutral glycosphingolipids extracted from rabbit liver plasma membrane by enzyme-linked immunosorbent assay and thin-layer chromatography immunostaining. IgG class antibody to neutral glycosphingolipids was detected in 29.6% (8 of 27), 6.3% (1 of 16), 0% (0 of 8), 0% (0 of 25), and 6.9% (2 of 29) in the sera of patients with HCC, liver cirrhosis, autoimmune chronic active hepatitis, chronic hepatitis, and normal individuals, respectively. Using the serum positive for the antibody to neutral glycosphingolipids, the target antigen glycolipid was isolated. Negative ion fast atom bombardment mass spectrometry, exoglycosidases treatment, and permethylation analysis revealed that the main target antigen was IV3 alpha Gal-nLc4Cer. In enzyme-linked immunosorbent assay, IgG class antibody to IV3 alpha Gal-nLc4Cer was detected in 33.3% (9 of 27), 18.8% (3 of 16), 25% (2 of 8), 4% (1 of 25), and 6% (3 of 50) in the sera of patients with HCC, liver cirrhosis, autoimmune chronic active hepatitis, chronic hepatitis, and normal individuals, respectively. Of 9 HCC patients positive for the antibody, 6 had received transcatheter arterial embolization (TAE) therapy. Six of 10 patients who received TAE therapy had the antibody, whereas only 3 of 17 patients without TAE therapy had the antibody. This antibody may be a heterophile antibody, which recognizes Gal alpha 1-3Gal structure at the nonreducing terminal of the antigen. Since the occurrence of this antibody was closely related with TAE therapy, the necrosis of HCC induced by TAE therapy may stimulate the production of the antibody.
Animals↗
Characterization of Rose Bengal binding to sinusoidal and bile canalicular plasma membrane from rat liver.
The binding of Rose bengal, a model organic anion, to sinusoidal and bile canalicular membrane fractions isolated from rat liver was compared. The fluorescence change of Rose bengal after being bound to liver plasma membranes was utilized for measuring the binding. The dissociation constants (Kd = 0.1-0.12 microM) and the binding capacities (n = 11-15 nmol/mg protein) for Rose bengal are comparable between the two membrane fractions, although the n value for sinusoidal membrane is somewhat larger than that for bile canalicular membrane. The Rose bengal binding to both membrane fractions was inhibited by various organic anions at relatively low concentrations, i.e., the half-inhibition concentrations (IC50) for Indocyanine green, sulfobromophthalein, Bromophenol blue and 1-anilino-8-naphthalene sulfonate were 0.1, 100, 1.5-2.5 and 100 microM, respectively, while taurocholate did not inhibit the Rose bengal binding to either membrane fraction at these low concentration ranges. The type of inhibition of sulfobromophthalein and Indocyanine green for Rose bengal binding is different between the two membrane domains. That is, in sinusoidal and bile canalicular membrane fractions, these organic anions exhibit mixed-type and competitive-type inhibition, respectively. It was suggested that the fluorescence method using Rose bengal may provide a simple method for detecting the specific organic anion binding protein(s) in the liver plasma membrane.
Anilino Naphthalenesulfonates↗
Calcium-activated neutral protease inhibitor (E-64c) and reperfusion for experimental myocardial infarction.
We examined the efficacy of the combination of coronary reperfusion and calcium-activated neutral protease (CANP) inhibitor (E-64c) for the treatment of acute myocardial infarction in dogs. In 34 dogs, the left anterior descending artery (LAD) was occluded and reperfused after 1 hour (Groups A and B). In the remaining 49 dogs, the LAD was ligated (Groups C and D). E-64c (100 mg/kg, Groups A and C) or vehicle (Groups B and D) was injected intravenously before and after the coronary occlusion or ligation. After 24 hours the hearts were removed. The proportion of the infarct size in the LAD perfusing area (risk zone) in Group A was 47.3 +/- 9.7%, significantly lower than in Group C (54.8 +/- 8.2%, p less than 0.05) or Group D (58.7 +/- 10.0%, p less than 0.01). There was a significant difference between Group B (52.9 +/- 8.6%) and Group D as well (p less than 0.05). The effects of reperfusion (p = 0.0016) and E-64c (p = 0.0226) per se on infarct size were significant, but the combination of reperfusion and E-64c was not additive. The decrease in CPK activity in the risk zone was significantly lower in the reperfused group (p = 0.0001). The mCANP activity was higher in the border zone and lower in the infarct zone. The trend in the mu CANP activity was similar to that of mCANP. Thus, treatment with a CANP inhibitor in the early phase of acute myocardial infarction may be marginally beneficial in combination with reperfusion.
Animals↗
[Clinical evaluation of the prehospital phase of acute myocardial infarction in the elderly].
In order to clarify the clinical characteristics of the prehospital phase of acute myocardial infarction (AMI) in the elderly, we studied 92 elderly (65 years old or more) and 41 younger patients with first AMI. Fifty eight elderly (63.1%) and 30 younger (72.7%) patients had typical symptoms such as chest pain at onset. There were 5 elderly cases who had no symptom, although all of the younger had some symptoms at onset. More than 70% of the younger cases developed their symptoms either between 6 am and noon or between 6 pm and midnight, whereas the elderly showed no such tendency. Intervals between the onset of symptoms and hospital admission (admission time) averaged 6.8 hours (hr) in the younger and 7.7 hr in the elderly. Approximately one half of the elderly and a quarter of the younger showed admission time more than 6 hr, respectively. Elderly cases with atypical symptoms tended to have a longer admission time than younger cases (7.2 vs 3.1 hr), although there was no significant difference between the elderly and the younger with typical symptoms (8.0 vs 7.9 hr). Younger patients with heart failure had significantly shorter admission time than those without heart failure (3.6 vs 8.6 hr). However, the elderly with heart failure showed a prolonged admission time (6.1 hr). Although there was no difference on admission time between survivors and non-survivors within 28 days after admission in the elderly (7.5 vs 8.4 hr), the elderly non-survivors with atypical symptoms had the longest admission time (13.0 hr).(ABSTRACT TRUNCATED AT 250 WORDS)
Age Factors↗
[Clinical course and prognosis of primary biliary cirrhosis--multivariant analysis on cases of national survey].
In order to predict prognosis and clinical course of BPC, theory quantification was applied and the discriminated rate was calculated concerning the cases of PBC national survey in Japan. We examined the prediction of three and five year's survival about all cases, the prediction of appearance of symptoms about asymptomatic PBC and that of jaundice about asymptomatic PBC and symptomatic PBC alone with pruritus. The useful items for the prediction of prognosis were serum bilirubin, albumin and the presence of esophageal varices at first medical examination. Fairly good discriminated rate was obtained on the prediction of three and five year's survival. However poor results were obtained concerning the prediction of appearance of symptoms. In conclusion we can predict the prognosis of PBC based on clinical features.
Aged↗
Fibroblast-like transformation and c-myc gene alteration of human hepatocytes induced by novobiocin and butyrate.
Topoisomerase II inhibitor novobiocin and deacetylase inhibitor sodium butyrate synergistically transformed Chang liver cells into fibroblast-like cells. In these fibroblast-like cells, the production of type III procollagen was increased and the DNase I hypersensitivity of c-myc gene was reduced. In addition, these changes were associated with an increased acetylation of nuclear proteins, especially those of DNase I sensitive nucleosomes. Therefore, it is suggested that chemical modulation of nuclear proteins by novobiocin and butyrate may be responsible, at least partly, for the alteration of the chromatin structure of c-myc gene and the fibroblast-like transformation of Chang liver cells.
Butyrates↗
[The clinical and pathological study in the recurrent myocardial infarction].
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Aged↗
Comparison of bile acid binding to sinusoidal and bile canalicular membranes isolated from rat liver.
Simon et al. (J. Clin. Invest., 70 (1982) 401) studied cholate binding to crude liver plasma membrane vesicles and suggested that the binding may represent mainly the binding to the receptor (carrier) on the canalicular membrane. This hypothesis was supported by finding a good correlation between the number of cholate binding sites on liver plasma membrane and the maximal rate of biliary secretion (Tm) for taurocholate. We studied bile acid binding to sinusoidal and canalicular membrane vesicles isolated from rat liver by a rapid filtration technique. Scatchard analysis of the saturation kinetics showed both [3H]cholate and [3H]chenodeoxycholate bind to two classes of binding site on each membrane. However, little difference was observed between the binding to sinusoidal and canalicular membrane vesicles for each bile acid (cholate, Kd1 = 10.4 and 19.8 microM, n1 = 31.0 23.6 pmol/mg protein, Kd2 = 1.32 and 1.73 mM, n2 = 13.1 and 23.4 nmol/mg protein; and chenodeoxycholate, Kd1 = 0.207 and 0.328 microM, n1 = 36.7 and 27.4 pmol/mg protein, Kd2 = 1.16 and 2.26 mM, and n2 = 20.6 and 24.2 nmol/mg protein; numbers show the mean values sinusoidal and canalicular membrane vesicles, respectively). Chenodeoxycholate binding to sinusoidal membrane vesicles was markedly inhibited by cholate but not by Rose bengal, an organic anion dye. These studies indicate that both membranes (sinusoidal and canalicular membrane vesicles) have two kinds of binding site for bile acids, although no clear difference in the binding properties was observed between the two membranes. Consequently, the cholate binding Simon detected may represent the binding not only to canalicular membrane vesicles but also to sinusoidal membrane vesicles.
Animals↗
Effects of teleocidin on the morphology and c-myc expression of hepatoma cells which are not inhibited by protein kinase antagonists.
PLC/PRF/5 hepatoma cells cultured with a tumor promoter teleocidin showed polygonal cellular appearance with many vacuole-like structures, and reduced both c-myc mRNA level and growth rate. These teleocidin effects were partly mimicked by sodium butyrate but not by a protein kinase C stimulant 1-oleoyl-2-acetylglycerol(OAG). Protein kinase C inhibitor 1-(5-isoquinolinyl-sulfonyl)-2-methyl-piperazine(H7), calmodulin-dependent protein kinase antagonist N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide(W7) and topoisomerase II inhibitor novobiocin failed to inhibit the effects of teleocidin. These results may suggest the presence of still unknown biochemical pathways which mediate the actions of teleocidin.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Antibody that recognizes conformations of calmodulin in the serum from patient with chronic active hepatitis.
According to the effects of Ca++ on the reactivity, anti-calmodulin antibody in the sera of patients with autoimmune chronic active hepatitis was classified into three types, which were tentatively designated as type 1, 2 and 3. Type 1 antibody reacted with calmodulin only in the presence of free Ca++. Binding of type 2 antibody to calmodulin was inhibited by the presence of free Ca++. Type 3 antibody reacted with calmodulin regardless of the presence or absence of free Ca++. Thus the sera contained the populations of the antibody which recognized the different conformations of calmodulin molecule.
Autoantibodies↗
Effects of calmodulin antagonists on secretion of bile and bile acid.
In the isolated perfused rat liver, the effects of calmodulin (CaM) antagonists, chlorpromazine (CPZ), trifluoperazine (TFP), W-7 and W-5, on secretion of bile and bile acid were compared. Without addition of taurocholic acid to the perfusate, TFP (200 microM or higher), CPZ (200 microM) and W-7 (400 microM) decreased the bile flow transiently. In contrast, W-5 did not decrease the bile flow. Taking into consideration the binding of TFP and CPZ to bovine serum albumin in the perfusate, they diminished the bile flow by inhibiting CaM function. This was also supported by the difference between the effects of W-7 and W-5. These findings suggested that CaM was involved in the secretion of bile. Under the constant infusion of taurocholic acid into the perfusate, CaM antagonists decreased the secretion of bile acid. However this might be due to the inhibition of bile acid uptake, because these agents inhibited the uptake into isolated rat hepatocytes. The concentrations required for inhibition of the uptake were near to those which decreased the viability, suggesting that the inhibition was due to their non-specific cytotoxic effect. Future studies must be carried out to determine whether CaM is involved in the secretion of bile acid.
Animals↗
A diagnostic marker of autoimmune chronic active hepatitis: liver plasma membrane antibody in the serum absorbed with particulate fraction of kidney homogenate.
The sera absorbed with the particulate fraction of rabbit kidney homogenate (RK) were tested for the antibody against liver plasma membrane (LPM-Ab) by the radiometric assay method. After incubation of the isolated rabbit liver plasma membrane (RLPM) with appropriately diluted serum, IgG bound to RLPM (IgG-RLPM) was determined using 125I-labelled Staphylococcal protein A. IgG-RLPM in each subject tested was expressed in arbitrary units, that is, the multiple of the mean radioactivity associated with RLPM in 35 control subjects. Thus IgG-RLPM was 1.00 (mean) +/- 0.23 (SD) in the control subjects, 1.13 +/- 0.30 in 9 patients with chronic persistent hepatitis (CPH), 1.13 +/- 0.52 in 15 with chronic active hepatitis (CAH), 1.34 +/- 0.38 in 23 with liver cirrhosis (LC) and 3.45 +/- 0.73 in 5 with autoimmune CAH. F(ab')2 fragments from a patient with autoimmune CAH and a control subject decreased IgG-RLPM by 86.4 +/- 6.35 and -5.2 +/- 14.9%, respectively, in four patients with autoimmune CAH. LPM-Ab was detected in 0, 20.0 and 17.4% in the patients with CPH, CAH and LC, respectively. All of the patients with autoimmune CAH were positive for LPM-Ab. The absorption of the sera positive for LPM-Ab with RK decreased IgG-RLPM in various extents. In two of five patients with autoimmune CAH and two of seven patients with CAH or LC, the majority of LPM-Ab was cross-reactive with RK.
Animals↗