Hepatitis delta virus and autoantibodies to epithelial cells.
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Antibodies, Monoclonal↗
Biomedical subjects
E Pisi
Publications and source records attributed to E Pisi.
A rapid method for the in vivo measurement of liver volume.
A method is described to calculate liver volume at US using real-time equipment. The method is based on the measurement of the 3 maximum diameters of the liver. Equations were derived by correlation vs CT volume measurement using the 3 diameters (multiple regression) or their product (simple regression) as independent variables in 20 subjects with and without liver disease. It is suggested that liver volume may be estimated as: y = -2364 + 89.2.(C-C) + 119.9.(A-P) + 59.6.(L-L) or y = 133.2 + 0.422.(C-C.A-P.L-L) where y is the volume (in ml), and C-C, A-P, and L-L are the 3 diameters (in cm). The two equations were validated in a second set of 22 subjects. US volume estimated according to Eq. 2 explained approximately 82% of the variance of the actual liver volume. The method is reproducible (interobserver variations less than 8%), rapid and easy-to-repeat. These features make it potentially useful in prospective longitudinal studies.
Adult↗
Serum antibodies to thymus epithelial cells in non-A, non-B and cryptogenic chronic liver disease.
Antibodies against thymus epithelial cells (anti-TEC) and the basal cell layer (BCLA) of squamous epithelia have been described in association with HDV-related chronic liver disease (CLD). Data are lacking on their presence during nAnB virus infection. Sera from 51 patients with nAnB post-transfusion hepatitis, including acute and chronic cases diagnosed during a prospective study on candidates for cardiac surgery, and 167 with various forms of CLD were tested for the presence of anti-TEC and BCLA using indirect immunofluorescence on human thymus and rat forestomach sections. Both antibodies mainly occurred in nAnB, HDV and cryptogenic CLD (anti-TEC: 51%, 47% and 42%; BCLA: 29%, 38% and 31%, respectively). The prevalence of anti-TEC in nAnB CLD turned out to be higher than that recorded in alcoholic, HBV-related, autoimmune, liver and kidney microsomal antibody positive CLD and primary biliary cirrhosis (p ranging from less than 0.03 to less than 0.0004). Two monoclonal antibodies (Mabs) to cytokeratins gave a pattern superimposable on that of spontaneous anti-TEC (both Mabs) and BCLA (only one). Antibodies against epithelial constituents, presumably targeting cytokeratin-associated antigens, occur not only in HDV CLD, as previously reported, but also in nAnB CLD, where they might represent a diagnostic aid, due to the unavailability of reliable serological markers of nAnB infection. The close similarity of anti-TEC and BCLA status between nAnB and cryptogenic CLD suggests a nAnB etiology of at least a proportion of chronic liver patients at present scored as cryptogenic.
Acute Disease↗
Portal blood velocity and flow in aging man.
The portal blood velocity and flow were measured by means of pulsed echo-Doppler in 60 normal subjects of 4 different age groups (less than or equal to 40, 41-55, 56-70, greater than or equal to 71 years). All subjects had normal routine liver function tests and no history of liver disease. Portal blood velocity decreased from 15.7 +/- 3.2 cm/s in younger subjects to 12.4 +/- 1.7 in subjects over 71 years (ANOVA: p = 0.005). Similarly portal blood flow decreased (p = 0.025). Both portal blood velocity and flow were inversely correlated with age (r = -0.583 and -0.505, respectively). No changes in portal vein diameter were observed. The age-related decline in portal flow may account for the decrease in hepatic blood flow previously documented in the elderly.
Adult↗
Antigen presenting cells in liver biopsies from patients with primary biliary cirrhosis.
Although Langerhans, interdigitating and follicular dendritic cells have been occasionally identified in pathological human liver by ultrastructural morphology, no data are available on their phenotypical their phenotypical identification using monoclonal antibodies. Frozen normal liver samples and biopsies from patients with primary biliary cirrhosis, primary sclerosing cholangitis and chronic active hepatitis were studied using a panel of 12 monoclonal antibodies (including anti class II antigens, follicular dendritic, macrophage and Langerhans cells). In normal liver, class II positive cells were represented by Kupffer and portal tract histiocytes with a macrophage phenotype. In pathological portal tracts non lymphocytic class II positive cells were represented by macrophages, clusters of follicular dendritic cells (which were detected in close association with B cell aggregates), and by sparse Langerhans cells (localized in areas of piecemeal necrosis and in a periductal position or infiltrating class II positive bile ducts). The present data suggest that both classical antigen presenting cells and class II positive bile duct cells may play some role in the induction of autoimmune reactions.
Antigen-Presenting Cells↗
Counterimmunoelectrophoresis (CIE) for the detection of anti-liver-kidney microsome (LKM) antibodies in the sera of patients with chronic liver disease.
A counterimmunoelectrophoresis (CIE) test for the detection of liver-kidney microsome specific antibodies in human sera is described. By testing different subcellular preparations the LKM antigen was found in the membranes of the smooth endoplasmic reticulum subfraction. The antigen was sensitive to trypsin digestion and behaved as an anionic protein in the experimental conditions used in the test. All sera positive for LKM in immunofluorescence gave a precipitin line of identity while none of the control sera gave a positive reaction. The CIE titers ranged between neat and 1/4096. A significant correlation was observed between the LKM titers obtained in immunofluorescence and those obtained in CIE. Moreover, by absorption experiments, it was concluded that the antigen preparation reactive in CIE was able to abolish the immunofluorescence pattern of LKM positive sera on rat liver and kidney sections. The LKM target antigen, although previously considered a structural protein of microsomal membranes, was shown to solubilize spontaneously during the isolation of microsomal membranes. Counterimmunoelectrophoresis appears to be an appropriate test for anti-LKM antibodies in human sera.
Autoantibodies↗
Desmin and actin in the identification of Ito cells and in monitoring their evolution to myofibroblasts in experimental liver fibrosis.
It has been reported that myofibroblasts contain actin and that Ito cells are positive for desmin. The distribution of desmin and actin detected by immunofluorescence, of vitamin A autofluorescence and of Sudan III staining of lipid droplets has been evaluated in sequential stages of experimental liver fibrosis induced in rats by intraperitoneal injections of swine serum. In the normal rat liver Ito cells were positive for desmin and weakly positive for actin. Prior to the development of hepatic fibrosis a clearcut increase in number and desmin staining of lobular Ito cells was observed in treated rats, but the overall actin pattern was unchanged. In the fibrotic rat livers, highly cellular septa contained large numbers of strongly desmin-positive, actin-weakly positive Ito cells and strongly desmin- and actin-positive myofibroblasts. These observations indicate that both Ito cells and myofibroblasts are positive for desmin, but only myofibroblasts contain large amounts of actin. Visualization of actin and desmin using relatively simple techniques, allows the monitoring of Ito cells proliferation, the accumulation of these cells in fibrous septa and their evolution into myofibroblasts as characterized by their increased desmin and actin content; it also allows an indirect evaluation of the process of fibrogenesis.
Actin Cytoskeleton↗
Caffeine intake, fasting plasma caffeine and caffeine clearance in patients with liver diseases.
The effects of a variable daily administration of caffeine on fasting levels of caffeine in plasma and in saliva were measured in 24 patients with liver disease and hepatocellular dysfunction of variable degree. For 2 consecutive days the patients received either 250 mg of caffeine (in 2 separate doses of 125 mg each at 8:00 a.m. and at 6:00 p.m.) or a single dose of 125 mg at 6:00 p.m. Caffeine clearance was also measured and the results were correlated with the galactose elimination capacity and with antipyrine clearance. At the beginning of the study, fasting caffeine concentrations were largely variable, without any relation to liver function. A strict negative correlation between fasting caffeine and caffeine clearance was only observed after 2 days of controlled caffeine administration (rs = -0.814). Under these conditions, fasting caffeine also correlated with antipyrine clearance (rs = -0.671, n = 20) and with galactose elimination (rs = -0.565). Our data prove that fasting caffeine concentrations after an evening dose may be used as an index of liver function only in subjects under a strictly controlled dietary caffeine intake. The large availability of caffeine in the diet makes the compound scarcely reliable for a correct measurement of liver function based on a single sample, and correct clearance determination is needed.
Body Weight↗
Heterogeneity of antimitochondrial antibodies with the M2-M4 pattern by immunofluorescence as assessed by Western immunoblotting and enzyme linked immunosorbent assay.
Seventy seven sera with antimitochondrial antibody exhibiting the M2-M4 pattern in immunofluorescence (56 from primary biliary cirrhosis (PBC), 21 from non-primary biliary cirrhosis patients) were studied by the combined use of Western immunoblotting with beef heart mitochondria and an enzyme linked immunosorbent assay (ELISA) with beef heart submitochondrial particles. Forty seven sera (10 without autoantibodies and 37 with different auto-antibodies) were included as controls. By immunoblotting, seven mitochondrial peptides reacting with antimitochondrial antibody positive sera were detected. These were of molecular weight 74 kD, 58 kD, 55 kD, 52 kD, 51 kD, 46 kD, and 43 kD. All primary biliary cirrhosis sera and 71% of antimitochondrial antibody-positive non-primary biliary cirrhosis sera reacted with one or more of these peptides, while none of the 47 antimitochondrial antibody negative sera reacted in immunoblotting. The 74 kD band was the most frequently detected (84% of primary biliary cirrhosis and 57% of non-primary biliary cirrhosis cases). All the primary biliary cirrhosis sera which failed to react with this peptide, showed a positive reaction with that of molecular weight 52 kD. 67/77 (87%) immunofluorescence antimitochondrial antibody positive sera reacted in the ELISA test (93% of primary biliary cirrhosis and 71% of non-primary biliary cirrhosis cases). All the 47 immunofluorescence antimitochondrial antibody negative sera were confirmed negative by ELISA. The ELISA values correlated with the immunofluorescence titres (p less than 0.05). By comparison of the results obtained by these two techniques, it emerged that the ELISA test (using our preparation of submitochondrial particles) was not able to detect the antibody directed against the mitochondrial peptide of 52 kD, which thus seems to be different from the other specificities.
Animals↗
Immunoglobulin A antigliadin antibodies in jejunal juice: markers of severe intestinal damage in coeliac children.
Antibodies to gliadin (AGA), detected in jejunal juice by immunofluorescence and enzyme-linked immunosorbent assay, have been found in 13 of 15 (87%) children with untreated coeliac disease. Jejunal AGA were also positive in 6 of the 9 (67%) coeliac children on gluten challenge, while they were consistently negative in coeliac children on a gluten-free diet and in controls. Jejunal AGA were always of immunoglobulin A (IgA) class, associated with IgM in some cases. Moreover, the presence of IgA AGA in jejunal juice was strictly related to the severity of intestinal damage. These data suggest that IgA AGA, detected in jejunal juice are synthesized from gut mucosa and are markers of its abnormal function. Like AGA, antibodies to milk and egg proteins were only found in jejunal juice of coeliac patients with flat intestinal mucosa, but their prevalence was significantly lower than that of AGA.
Celiac Disease↗
Correlation between complement-fixing islet-cell antibodies and the clinical onset of insulin-dependent diabetes.
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Autoantibodies↗
Clinical presentation of adult coeliac disease.
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Adolescent↗
Antigliadin and antireticulin antibodies in coeliac disease and at onset of diabetes in children.
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Adult↗
Insulin resistance is the main determinant of impaired glucose tolerance in patients with liver cirrhosis.
To clarify the pathogenesis of impaired glucose tolerance in patients with cirrhosis, several factors possibly affecting carbohydrate metabolism were studied in 12 cirrhotic patients with different blood glucose responses to an oral glucose tolerance test. Glucose levels, 120 min after the load, were inversely and significantly related to insulin sensitivity, measured by means of the euglycemic "glucose clamp" technique (r = -0.746). Basal and glucose-induced insulin secretion (insulin and C-peptide levels) only slightly correlated with glucose tolerance, which was not related to functional liver cell mass (galactose elimination), portal-systemic shunting (degree of varices at endoscopy), or maximal glucose-independent insulin secretion (peak C-peptide levels after a glucagon test). Multiple regression analysis identified insulin sensitivity and liver cell mass as the independent variables able to explain most of the variance of 120-min blood glucose (about 84%), and both of them contributed considerably to the regression. While reduced insulin sensitivity is probably the main cause of impaired glucose tolerance, the reduced hepatocellular mass only appears to modulate the degree, and therefore the clinical relevance, of this defect.
Adult↗
Insulin resistance in aged man: relationship between impaired glucose tolerance and decreased insulin activity on branched-chain amino acids.
The effects of glucose-induced hyperinsulinemia on plasma amino acid levels were measured in 50 subjects divided into five age groups. Following an oral glucose load the plasma levels of most amino acids decreased, the decline being more pronounced for the three branched-chain amino acids (valine, isoleucine, and leucine). A progressive insulin resistance was proved on the basis of an age-related impaired glucose tolerance and a normal or increased insulin response. The plasma disappearance of branched-chain amino acids significantly correlated with age (r = -.514). The effects of the prevailing plasma insulin on branched-chain amino acids, measured by the ratio of amino acid changes per total insulin response, progressively declined in older subjects (P = .0005), and strictly correlated with age (r = .652). Insulin resistance in the elderly similarly affects glucose and branched-chain amino acid metabolism, with possible relevant effects on whole-body protein turnover.
Aged↗
Non-invasive 24-hr monitoring of high blood pressure in climacteric outpatients.
Blood pressure (BP) monitoring was carried out over a period of 24 hr in 28 hypertensive women selected among the outpatients attending the Menopause Clinic at Bologna University. Seven (7) of the women (mean age 50 +/- 1 yr) were in the pre-menopause, 7 had undergone a natural menopause at 6 to 36 mth previously (mean age 52 +/- 4 yr) and a further 7 had had a natural menopause 37-120 months previously (mean age 56 +/- 5 yr). The control group was made up of 7 women in late fertile age (mean age 47 +/- 1 yr). It was found that: high blood pressure was not confirmed in all patients; there was a significant increase in systolic and diastolic BP values in natural post-menopause subjects (P less than 0.01) temporarily related to ovarian failure, but BP reached a steady state in elderly women when a new hormonal balance is established; 24-hr monitoring made it possible to identify a group of climacteric outpatients at higher cardiovascular risk whose suitability for antihypertensive treatment could thus be assessed.
Blood Pressure↗
Precipitating antibodies to rabbit thymus extractable antigens in chronic liver disease: relationship with anti-actin antibodies.
Using counterimmunoelectrophoresis (CIE), serum antibodies to rabbit thymus extractable antigens were detected in 15% (38/259) of patients with chronic liver disease (CLD) of various aetiologies and 33% (41/124) of patients with miscellaneous connective tissue diseases (CTD). A remarkable diversity of precipitating systems was apparent among cases with the two classes of disorders. All the five systems found in CLD (XR, XR2, SS-B, XR3, XR4) were associated mostly with immunological hepatic disorders. In the 52 autoimmune hepatitis cases, XR was mainly detected (29%), whereas in the 82 primary biliary cirrhosis patients the whole spectrum of reactivities was represented (XR: 11%, XR2: 10%, SS-B and XR3: 2% each, XR4: 1%). XR proved to be closely associated with smooth muscle antibodies (SMA, detected by indirect immunofluorescence on rat kidney sections) both qualitatively and quantitatively. Since all SMA positive sera with anti-actin specificity (SMAT, SMAG) were XR positive and purified actin could absorb out XR CIE reactivity, the hypothesis is made that a cross-reaction occurs between XR antigen and actin epitope(s).
Actins↗
HLA-A,B,C, HLA-D/DR and HLA-D/DQ expression on unfixed liver biopsy sections from patients with chronic liver disease.
The distribution of HLA-A,B,C, HLA-D/DR and HLA-D/DQ molecules was studied by indirect immunofluorescence with an avidin-biotin technique and monoclonal antibodies, in unfixed cryostat sections of liver biopsies from 76 patients with chronic liver diseases of various aetiologies and five normal liver biopsy specimens. In pathological liver, strong cytoplasmic or membrane-like positivity for HLA-A,B,C of hepatocytes was observed in piecemeal necrosis areas in all groups. Cytoplasmic staining was mainly seen in lobular areas in autoimmune, cryptogenic and HBV-related cases with viral replication, while membrane-like positivity was more frequently observed in primary biliary cirrhosis, alcoholic and HBV-related cases without viral replication. A weak cytoplasmic staining for HLA-D/DR was observed in piecemeal necrosis and lobular areas mainly in HBV-related cases with viral replication. While bile duct cells were positive for both HLA-D/DR and HLA-D/DQ, hepatocytes were consistently HLA-D/DQ negative. The increased HLA-A,B,C expression on hepatocytes should allow T cytotoxic cell aggression. Hepatocellular HLA-D/DR expression is definite but weak and probably does not allow direct autoantigen presentation and induction of autoimmunity. Negativity for HLA-D/DQ further supports this hypothesis. Since cytoplasmic staining for Class I and II molecules is greatly lowered by fixing cryostat liver sections, prestaining conditions should be taken into account when comparing different studies.
Bile Ducts↗