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Biomedical subjects

M Baraldini

Publications and source records attributed to M Baraldini.

At least 55 records · Page 3Linked to original sources

T lymphocyte subsets implicated in cytotoxicity in autologous hepatocytes in chronic active hepatitis patients with active viral replication.

We investigated inhibitory effect of various monoclonal antibodies on T-cell-mediated cytotoxicity against autologous hepatocytes in 24 patients with hepatitis B surface antigen/hepatitis B e antigen (HBsAg/HBeAg)-positive chronic active hepatitis. A significant reduction of cytotoxicity index occurred after preincubation of T lymphocytes with anti-Leu 7 (killer-natural killer cells), D1/12 (Ia-positive cells), 5/9 (restricted helper/inducer cells), and MLR4 ("activated" and radiosensitive helper cells) monoclonal antibodies (MAb). Anti-Leu 2a (cytotoxic/suppressor cells) and anti-Leu 3a (helper/inducer cells) MAb did not affect cytotoxic activity. This finding supports the hypothesis that the T cytotoxic reaction in this in vitro system is probably due to two mechanisms: first, spontaneous cell membrane cytotoxicity sustained by anti-Leu-7-positive lymphocytes; and second, specific cytotoxicity mediated by activated Ia-positive cells. We also found that the presence of helper/inducer cells (5/9 positive) appears to be a prerequisite for the cytotoxic reaction.

Adult↗

Liver-specific autoantibodies in chronic hepatitis B virus infection.

Anti-liver-specific protein (LSP) antibody and liver membrane autoantibody (LMA) have been evaluated in 88 patients with hepatitis B virus (HBV)-induced chronic liver disease by means of radioimmunoprecipitation and immunofluorescence. Among our patients, 38 presented circulating HBe antigen while 43 had HBe antibody and seven were negative for both. Anti-LSP was mainly found in HBeAg positive chronic active hepatitis (CAH), anti-HBe in positive CAH and in anti-HBe positive chronic persistent hepatitis (CPH). Similar prevalences of LMA (range 13-33%) were detected in the various groups studied. Taking into account the histological diagnosis of disease activity (periportal inflammation and piecemeal necrosis) no significant differences were found between active and inactive patients. Taking into account the HBeAg/anti-HBe status, no significant differences were found between the patients positive for 'e' antigen or 'e' antibody. Humoral autoimmune reactions may also play a role in HBV-induced chronic (active) liver disease irrespective of HBeAg/anti-HBe status and hence of the viral replication activity of the patients.

Autoantibodies↗

Renal function impairment induced by change in posture in patients with cirrhosis and ascites.

The assumption of upright posture by patients with liver cirrhosis leads to striking activation of adrenergic and renin-angiotensin systems. The tilting-induced modifications in renal function of eight healthy controls and 14 untreated patients with liver cirrhosis and ascites were related to plasma concentrations of noradrenaline, renin activity and aldosterone. All patients had preserved renal blood perfusion. All parameters were evaluated during bed rest for two hours and in the sitting posture for one hour. Basal plasma renin activity (0.1 greater than p greater than 0.05), aldosterone and noradrenaline concentrations (p less than or equal to 0.01) were raised in cirrhotics. The renal function tests (creatinine clearance, filtered sodium, tubular rejection fraction, urinary sodium excretion) were significantly reduced in cirrhosis. Under basal conditions, in cirrhotic patients tubular rejection fraction and urinary sodium excretion were inversely related to both noradrenaline and aldosterone concentrations. After tilting, the noradrenaline and aldosterone integrated outputs (sigma delta) were significantly greater in cirrhosis. All renal function tests significantly decreased in cirrhotics, whereas creatinine clearance only significantly decreased in controls. Patient's tubular rejection fraction of sodium and sodium excretion were related to sigma delta aldosteronaemia (r = -0.72; p less than 0.01), but no longer to sigma delta plasma noradrenaline.

Adult↗

Oxmetidine (SK&F 92994): pharmacokinetic study in patients with in patients with liver cirrhosis.

The pharmacokinetics of oxmetidine (SK&F 92994) were investigated in nine cirrhotic patients and compared with ten control subjects with gastroduodenal ulcers, but without any symptoms of hepatic pathology. On two separate occasions each patient received 200 mg oxmetidine as a single oral dose and 100 mg as a single intravenous dose. In the cirrhotics, the bioavailability of the oral dose and the plasma elimination half-life after both oral and intravenous administration were significantly higher than in the controls. Moreover, a positive correlation was found between the plasma elimination half-lives and the biochemical parameters of cholestasis. Such findings indicate that in severe liver disease and in cholestasis the accumulation of oxmetidine in the circulation may limit the use of this drug.

Aged↗

Circulating hepatocyte membrane-specific autoantibodies in chronic active hepatitis type B. Relation to virus replication activity and liver cell necrosis.

Sera from two groups of untreated HBsAG-positive patients with chronic active hepatitis on liver biopsy were tested for antibodies to liver cell membrane antigens (liver-specific protein, LSP; and liver membrane antigen, LM-Ag). Among the 14 HBeAg-positive cases, seven (50%) were positive for anti-LSP, whereas only two (13%) of 15 anti-HBe-positive cases circulated this antibody. Liver membrane autoantibody (LMA) was detected only in two sera from delta-positive patients (1 HBeAg positive and 1 anti-HBe positive). Anti-LSP-positive patients presented transaminase values significantly higher than those of the negative cases. Our data do not support the hypothesis that a liver-specific autoimmune mechanism plays a significant role in the immunopathogenesis of liver cell necrosis in anti-HBe-positive chronic active hepatitis type B. The relationship between hepatocyte necrosis and anti-LSP antibody response is confirmed.

Adult↗

Hepatitis B virus markers in hematologic patients: relation to transfusion treatment and hospitalization.

Screening tests for hepatitis B virus (HBV) markers were performed in 266 hematologic patients in order to evaluate the role of transfusion therapy in HBV infection and to identify other possible causes of the high rate of HBV markers positivity in oncohematologic units. As control groups we tested 99 nonhematologic polytransfused patients, 66 nonhematologic, nontransfused inpatients with various diseases and 72 subjects randomly selected from the general population. Higher HBV markers prevalence was found in hematologic patients, nonhematologic polytransfused patients and nonhematologic, nontransfused inpatients than in the general population. HBV markers prevalence correlated with the length of hospitalization in all inpatients studied. Our data suggest that hospital admission is a major factor in HBV transmission in hematologic patients and in other inpatients studied. Blood transfusions represent a risk factor only when utilized as chronic treatment.

Adolescent↗

Lymphocytotoxicity against autologous hepatocytes and membrane-bound IgG in viral and autoimmune chronic active hepatitis.

Membrane-bound IgG and lymphocytotoxic activity of total, T-enriched and T-depleted lymphocytes, using autologous hepatocytes have been evaluated in: (a) 31 patients with chronic active hepatitis (CAH) (six autoimmune and 25 hepatitis B virus - HBV-related); (b) five patients with inactive alcoholic cirrhosis; and (c) nine subjects with normal hepatic histology. Lymphocytotoxicity was positive in 83% of autoimmune CAH and 68% of HBV-related cases; it was confined to the T-depleted subpopulation in the first group, while it was present in both the T-enriched and T-depleted subpopulations in 81% of HBV-related cases. Membrane-bound IgG was present in 58% of group (a) and in none of the other groups. A linear pattern was found in four out of five autoimmune CAH patients with positive lymphocytotoxic activity. The autoimmune patient with lymphocytotoxic activity within the normal range did not show any membrane fluorescence. Among HBV-related CAH patients, 13 presented a granular pattern, two an associated granular and linear pattern and ten were negative. These data suggest that different lymphocytotoxic mechanisms are involved in the two forms of CAH studied.

Autoantibodies↗

Occurrence and significance of IgG liver membrane autoantibodies (LMA) in chronic liver diseases of different aetiology.

The prevalence of liver cell membrane antibodies (LMA) was evaluated in the sera of 124 untreated patients with various chronic liver diseases, in 17 acute hepatitis patients and in 40 normal controls by indirect immunofluorescence on rabbit hepatocytes, isolated by non-enzymatic method. The presence of LMA was compared with the presence of HBs Ag, anti-HBc and non-organ specific autoantibodies (anti-nuclear antibody, ANA; smooth muscle antibody, SMA; anti-mitochondrial antibody, AMA; liver-kidney microsomal antibody, LKM). LMA was found in 83% of autoimmune chronic active liver disease (CALD), in 47% of cryptogenic CALD and in 42% of primary biliary cirrhosis (PBC). LMA prevalence both in HBsAg positive and HBsAg negative/anti-HBc positive CALD was 11%, significantly lower than in the other three groups. In the cryptogenic group the prevalence of non-organ specific autoantibodies was significantly lower than LMA prevalence. The 35 LMA positive sera were titred to end point dilution. Autoimmune cases presented titres higher than those of all the other groups. Adsorption experiments showed that in autoimmune cases LMA fluorescence is not blocked by pre-incubation with liver antigens LSP and LP2, while a mild blocking effect was observed in some HBsAg positive cases or PBC sera. No cross-reaction with mitochondrial antigens was observed in PBC sera. LMA can still be considered a marker of autoimmune CALD only when present at high titre and without cross-reactivity with other liver antigens.

Animals↗

[Effect of 2 mercaptopropionylglycine on the cytotoxic activity of lymphocytes from patients with chronic active hepatitis against rabbit hepatocytes isolated and cultured in vitro].

"In vivo" and "in vitro" action of 2 MPG on lymphocytotoxic activity was evaluated in 22 patients with CAH, 14 were HBsAg positive and 8 were negative. The test was performed with and without 2 MPG in the colture medium, and before and after treatment. HBsAg+ patients received 2 MPG treatment, while HBsAg- ones received immunosoppressive therapy and 4 of these were on 2 MPG treatment as well. Cytotoxic Index was reduced non-significantly by addition of 2 MPG in colture medium in both groups. 2 MPG treatment does not modify cytotoxic activity which is reduced by immunosoppressive therapy. These findings suggest a positive effect of 2 MPG on liver-cell metabolism with an increased resistence of the epatocyte to the "in vitro" lymphocytes aggression. Hence it may be suggested an association treatment with immunosoppressive agents and 2 MPG.

Amino Acids, Sulfur↗

Radioimmunoassay for hepatitis B 'e' antigen and antibody: correlations with viral replication and prognostic value.

The presence of hepatitis B 'e' antigen (HBeAg) and its antibody (anti-HBe was evaluated by radioimmunoassay (RIA) in various groups of HBsAg-positive patients. HBeAg was present in the majority of the sera from patients with acute viral hepatitis at onset of clinical symptoms and disappeared after 1 year. Almost all hemodialysis patients had HBeAg in their sera. 40% of the patients who had chronic active hepatitis and 50% with chronic persistent hepatitis had HBeAg with no relationship to the inflammatory activity of the disease evaluated by the presence of mononuclear infiltration in liver biopsy. The comparison between the presence of HBeAg and Dane particle-associated DNA-polymerase activity showed that HBeAg was consistently found in almost all the sera which presented DNA-polymerase activity. HBeAg, as determined by RIA, may therefore be useful in the screening of highly infective patients with elevated viral replication.

Antibodies, Viral↗

Antibodies against human liver-specific protein (LSP) in acute and chronic viral hepatitis types A, B and non-A, non-B.

Sera from 42 patients with acute viral hepatitis (AVH), 97 patients with chronic active liver disease (CALD) and 89 controls were tested by radioimmunoprecipitation for the presence of antibodies against human liver-specific protein (LSP). Anti-LSP were found in all but one patient with AVH type A (93%) and in a smaller percentage of AVH type B (55%). In non-A, non-B cases, anti-LSP were found in low percentages: 27% in acute cases, 10% in chronic cases. Furthermore, in CALD, a significant difference was found between HBsAg-positive CAH and 'autoimmune' CAH, a significant difference was found between HBsAg-positive CAH and 'autoimmune' CAH, both in anti-LSP prevalence (21%, 67%; P less than 0.005) and in anti-LSP titre (1:154 +/- 170, 1:316 +/- 186; P less than 0.005). In HBsAg-negative/anti-HBc-positive CAH, three of 15 patients were anti-LSP positive. Anti-LSP were found only in three of 57 patients with various non-hepatic diseases with autoimmune features. None of the 12 healthy HBsAg carriers was positive. Hence there is evidence for a considerable heterogeneity in anti-LSP response in acute and in chronic inflammatory HBsAg-negative liver diseases. These data suggest that anti-LSP antibodies do not play a prominent role in the process of transition to chronicity of acute viral hepatitis particularly in non-A, non-B cases, whereas these antibodies may be important in the mechanism of ongoing liver cell injury in patients with 'autoimmune' CAH, and can represent a useful diagnostic marker of this type of hepatitis.

Acute Disease↗

[Separation and characterization of human T G and T M lymphocyte populations].

During the last few years a number of experimental evidences have shown the presence of Fc receptors for IgG or IgM on the membrane of human T cells. These two different receptors are detectable and mutually exclusive on distinct cell populations named respectively TG, TM and T "null" (which lack detectable receptors). Studies on the functional activities of these cells have shown that TM and TG lymphocytes play an antitetical role in regulating B cell response, TM exerting an "helper" activity on the differentiation of B lymphocytes while TG having a "suppressor" one. The aim of this study has been to determine the values of these two subpopulations in a group of twenty control subjects. Our results have shown that TG constitute 10%, whereas TM represent 40% of the total T cells. After EA-G rosetting, the purification of this subpopulation on a density gradient has shown an enrichment of more than 90% in TG cells, while TM contaminate this fraction for less than 4%. The purity of the fraction containing TM has been evaluated using the localization of alpha-naphthyl acetate esterase activity, which has shown that more than 88% of the cells in this fraction are positive for this enzyme.

Adult↗