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Biomedical subjects

F Fiaccadori

Publications and source records attributed to F Fiaccadori.

At least 55 records · Page 3Linked to original sources
PubMed1992

Autopresentation of hepatitis B virus envelope antigens by T cells.

Processing and presentation by T cells appear to be limited to antigens that can directly interact with the T-cell surface, thereby overcoming the T-cell inefficiency in antigen capture and internalization. Our study provides evidence that the hepatitis B virus (HBV) envelope proteins can also be efficiently processed and presented by CD4+ and CD8+ T cells to other T cells in a human leukocyte antigen class II-restricted fashion. This phenomenon suggests a receptor-mediated interaction between T cells and the HBV envelope and defines a system that can, we hope, be exploited for the identification of the receptor binding site within the HBV envelope and for the characterization of the putative cellular HBV receptor.

Antigen-Presenting Cells↗
PubMed1991

HLA class I-restricted human cytotoxic T cells recognize endogenously synthesized hepatitis B virus nucleocapsid antigen.

Knowledge of the immune effector mechanisms responsible for clearance of hepatitis B virus (HBV)-infected cells has been severely limited by the absence of reproducible systems to selectively expand and to characterize HBV-specific cytotoxic T lymphocytes (CTLs) in the peripheral blood of patients with viral hepatitis. By using a strategy involving sequential stimulation with HBV nucleocapsid synthetic peptides followed by autologous, or HLA class I-matched, HBV nucleocapsid transfectants, we now report the existence of CTLs able to lyse target cells that express endogenously synthesized HBV nucleocapsid antigen in the peripheral blood of patients with acute viral hepatitis B. The CTL response is HLA-A2 restricted, mediated by CD8-positive T cells, and specific for a single epitope, located between amino acid residues 11 and 27 of HBV core protein; these residues are shared with the secretable precore-derived hepatitis B e antigen. Equivalent lysis of target cells that express each of these proteins suggests that their intracellular trafficking pathways may intersect. The current report provides definitive evidence that HLA class I-restricted, CD8-positive CTLs that recognize endogenously synthesized HBV nucleocapsid antigen are induced during acute HBV infection in humans and establishes a strategy that should permit a detailed analysis of the role played by HBV-specific CTLs in the immunopathogenesis of viral hepatitis.

B-Lymphocytes↗
PubMed1991

Cytotoxic T lymphocytes recognize an HLA-A2-restricted epitope within the hepatitis B virus nucleocapsid antigen.

The absence of readily manipulable experimental systems to study the cytotoxic T lymphocyte (CTL) response against hepatitis B virus (HBV) antigens has thus far precluded a definitive demonstration of the role played by this response in the pathogenesis of liver cell injury and viral clearance during HBV infection. To circumvent the problem that HBV infection of human cells in vitro for production of stimulator/target systems for CTL analysis is not feasible, a panel of 22 overlapping synthetic peptides covering the entire amino acid sequence of the HBV core (HBcAg) and e (HBeAg) antigens were used to induce and to analyze the HBV nucleocapsid-specific CTL response in nine patients with acute hepatitis B, six patients with chronic active hepatitis B, and eight normal controls. By using this approach, we have identified an HLA-A2-restricted CTL epitope, located within the NH2-terminal region of the HBV core molecule, which is shared with the e antigen and is readily recognized by peripheral blood mononuclear cells from patients with self-limited acute hepatitis B but less efficiently in chronic HBV infection. Our study provides the first direct evidence of HLA class I-restricted T cell cytotoxicity against HBV in humans. Furthermore, the different response in HBV-infected subjects who successfully clear the virus (acute patients) in comparison with patients who do not succeed (chronic patients) suggests a pathogenetic role for this CTL activity in the clearance of HBV infection.

Alanine Transaminase↗
PubMed1991

Short-term oral zinc supplementation does not improve chronic hepatic encephalopathy. Results of a double-blind crossover trial.

The effect of short-term oral zinc supplementation (zinc sulfate 600 mg/day) on hepatic encephalopathy, was assessed in a double-blind, crossover trial. Fifteen cirrhotic patients with stable, chronic hepatic encephalopathy were randomized to receive either oral zinc or a placebo for 10 days. Following a two-week washout period, these were crossed over to the alternate treatment. Conn's index, which comprises the evaluation of the mental state, asterixis, number connection test, EEG record, and plasma ammonia, was used to score the degree of hepatic encephalopathy, both at the beginning and end of each treatment period. Serum zinc was significantly raised after oral zinc administration and reached the levels observed in cirrhotics without hepatic encephalopathy. Despite this, however, no modification in the parameters included in Conn's index were observed. In conclusion, this study failed to confirm that short-term oral zinc supplementation improves chronic hepatic encephalopathy.

Administration, Oral↗
PubMed1991

Insulin and glucagon levels in fulminant hepatic failure in man.

The behavior of insulin and glucagon and related metabolic substrates was assayed in plasma of patients with fulminant hepatic failure. All 12 subjects were provided the same nutritional support. High levels of insulin and glucagon were present at all times and no difference was observed between surviving patients (four) and those who died (8). Elevated values for branched-chain and aromatic amino acids as well as alanine were present. Statistically significant lower levels of aromatic amino acids and consequently a greater branched chain-aromatic amino acid ratio was found in surviving vs nonsurviving patients. A significantly greater level of alpha-fetoprotein was found in patients who survived as compared to those who died.

Adult↗
PubMed1991

Rifaximin versus neomycin on hyperammoniemia in chronic portal systemic encephalopathy of cirrhotics. A double-blind, randomized trial.

Preliminary data suggest that rifaximin a new non-absorbable rifamycin-derivate, has beneficial effects on chronic portal systemic encephalopathy (PSE). To compare the efficacy and safety of rifaximin vs neomycin in the treatment of the hyperammoniemic state of PSE, 30 cirrhotic patients with grade I to III of PSE were randomly allocated to one of two groups: group A (15 patients) receiving rifaximin (400 mg/8h) and group B (15 patients) neomycin (1gr/8h). The duration of treatment was 21 consecutive days. Age, sex, hepatic and renal function, level of PSE, EEG and number connection test were similar in both groups. A significant decrease in blood ammonia levels was observed at the end of the treatment period in both groups; moreover rifaximin produced an earlier reduction of blood ammonia levels. The neuropsychic syndrome related to the PSE improved in both groups without significant difference. No side effects attributable to therapy were observed in the rifaximin group. These results indicate that, rifaximin is at least as effective as neomycin in the achievement and maintenance of low blood ammonia levels in cirrhotics with chronic PSE.

Aged↗
PubMed1990

Cellular immune response to hepatitis B virus-encoded antigens in acute and chronic hepatitis B virus infection.

The proliferative response of PBMC to hepatitis B virus (HBV) envelope, core, and e Ag was analyzed prospectively in 21 patients with acute self-limited HBV infection and compared with the response of patients with chronic HBV infection and different levels of HBV replication (i.e., hepatitis e Ag (HBeAg)- or anti-HBe-positive) and liver damage (i.e., chronic active hepatitis or chronic asymptomatic carriers). Our results indicate that: 1) HBV-infected subjects who develop a self-limited acute hepatitis show a vigorous PBMC response to hepatitis B core Ag and HBeAg, as expression of T cell activation; 2) appearance of a detectable lymphocyte response to HBV nucleocapsid Ag is temporally associated with the clearance of HBV envelope Ag; 3) in patients with chronic HBV infection the level of T cell responsiveness to hepatitis B core Ag and to HBeAg is significantly lower than that observed during acute infection; 4) T cell sensitization to HBV envelope Ag in acute and chronic HBV infection is usually undetectable and when measurable is expressed transiently and at low levels. These results may reflect immune events of pathogenetic relevance with respect to evolution of disease and viral clearance.

Adult↗
PubMed1990

Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. A double-blind, placebo-controlled study.

Parenteral S-adenosylmethionine proved to be effective in reversing intrahepatic cholestasis in pregnant women. Based on these findings, a prospective multicenter, double-blind, placebo-controlled trial was planned to assess whether oral S-adenosylmethionine is effective in cholestatic patients with chronic liver disease. Accordingly, 220 inpatients (26% chronic active hepatitis, 68% cirrhosis, 6% primary biliary cirrhosis) with stable (1 month or more) at least twofold increases in serum total and conjugated bilirubin and alkaline phosphatase volunteered for the trial. Serum markers of cholestasis significantly (P less than 0.01) decreased after oral S-adenosylmethionine administration (1600 mg/day), and their values were significantly (P less than 0.01) lower than the corresponding values in the placebo group. S-adenosylmethionine significantly (P less than 0.01) improved subjective symptoms such as pruritus, fatigue, and feeling of being unwell, whereas placebo was ineffective. Two patients in the S-adenosylmethionine group and 9 controls (P less than 0.05) withdrew from the trial for reduced compliance because of inefficacy of treatment. Oral S-adenosylmethionine was tolerated to the same extent as placebo. In conclusion, short-term administration of oral S-adenosylmethionine is more effective than placebo in improving clinical and laboratory measures of intrahepatic cholestasis and offers a new therapeutic modality for the symptomatic management of this syndrome.

Administration, Oral↗
PubMed1989

The preS1 antigen of hepatitis B virus is highly immunogenic at the T cell level in man.

14 hepatitis B vaccine recipients who showed high titers of anti-hepatitis B surface antibodies in serum after booster immunization with a polyvalent hepatitis B surface antigen vaccine that contained trace amounts of hepatitis B virus (HBV) preS1 and preS2 envelope antigens were studied for their in vitro T cell response to these antigens. All 14 subjects displayed a significant proliferative T cell response to the S/p25 envelope region encoded polypeptide; 8 also responded to preS1, while only 1 showed a significant level of T cell proliferation to preS2. Limiting dilution analysis demonstrated that the frequency of preS-specific T cells in two of these vaccine recipients was higher than that of S/p25-specific T cells. T cell cloning was then performed and a total of 29 HBV envelope antigen-reactive CD4+ cloned lines were generated from two preS-responsive vaccines. 21 of these lines were S/p25 specific, 7 preS1 specific, and 1 preS2 specific. Taken together, all these results suggest that the preS1 antigen may function as a strong T cell immunogen in man.

Chromobox Protein Homolog 5↗
PubMed1988

Clinical features of hepatitis delta virus infection in a northern Italian area.

Expression of hepatitis delta virus (HDV) markers was investigated in sera from 310 patients with acute hepatitis, 63 chronic hepatitis B surface antigen (HBsAg) carriers and 76 drug addicts positive for at least one serological hepatitis B virus (HBV) marker. Acute HDV infection occurred in 17.1% of the patients with acute hepatitis. Among 40 cases of coinfection, hepatitis was severe in ten and fulminant in three. Only two of the 13 superinfected patients showed a severe hepatitis, but a high percentage (78%) of them developed chronic hepatitis one year after HDV infection. Also in our area parenteral drug addiction represents the main factor of risk for HDV infection. The high prevalence of HDV infection in our area points to the necessity for serological screening for HDV markers in patients with acute and chronic hepatitis.

Acute Disease↗
PubMed1988

Cellular immune response to hepatitis B virus antigens. An overview.

It has been suggested that the cellular immune response to HBV antigens is responsible for hepatocellular injury in acute and chronic hepatitis B. However, definitive immunological studies have so far been hampered by the lack of appropriate model systems to study HBV antigen-specific T cells. The availability of highly purified and recombinant HBV antigens and of experimental techniques to maintain in continuous growth antigen-specific T cells derived not only from the peripheral blood but also from the liver should allow a better understanding of the fine immunopathogenetical mechanisms involved in viral clearance and liver damage. Whether some important biological characteristics of HBV antigens described in the mouse system, such as the high immunogenicity of the pre-S antigens and the capacity of the nucleocapsid of HBV to be a T cell-dependent and -independent antigen, are relevant to the immunopathogenesis of liver damage during natural HBV infection in man remains to be evaluated.

Animals↗
PubMed1987

Intrahepatic, nucleocapsid antigen-specific T cells in chronic active hepatitis B.

Hepatitis B core antigen (HBcAg)-specific T cell lines were established from hepatic lymphomononuclear cells derived from five patients with chronic active hepatitis B. No hepatitis B virus envelope antigen-specific cell lines were established. Proliferation in response to recombinant and native HBcAg, but not to native hepatitis B surface antigen containing the pre-S(2) region, confirmed the specificity of the five T cell lines. All cell lines represented mixed populations of CD4+ and CD8+ T cells. The CD4+ subset provided antigen-specific help to autologous B cells with respect to anti-HBc production and to CD8+ cells with regard to HBcAg-induced proliferation and suppressor activity. The CD8+ subset contained suppressor cells that selectively inhibited the proliferative response of autologous HBcAg-specific CD4+ cells without inhibiting CD4+ cells of unrelated specificity (tetanus toxoid). Moreover, the CD8+ cells were also capable of suppressing HBcAg-stimulated antibody to HBcAg production without showing inhibition of total immunoglobulin production stimulated by pokeweed mitogen. The cytotoxic potential of the T cell lines was established in a lectin-dependent cytotoxicity system; natural killer cytotoxicity was completely absent. Our data suggest that the lesional T cells present at the site of hepatocellular injury in chronic active hepatitis B are primarily HBcAg-specific lymphocytes of the helper and suppressor/cytotoxic phenotypes and that both are functionally competent.

Antibody Formation↗
PubMed1987

Functional characterization of cloned intrahepatic, hepatitis B virus nucleoprotein-specific helper T cell lines.

We have previously reported the establishment and preliminary characterization of polyclonal hepatitis B virus (HBV) nucleoprotein (HBcAg)-specific CD4+ and CD8+ T cell lines derived from the hepatic lymphomononuclear cell infiltrate of several patients with chronic active hepatitis B. The isolated subsets from these lines were specifically activated by HBcAg and displayed antigen-specific help and suppression with respect to proliferation of the alternate subset. One of these lines was recently cloned by limiting dilution, and four HBcAg-specific CD3+ CD4+ CD8-DR+ T cell lines were produced that had a 95.3% likelihood of monoclonality. Antigenic specificity was confirmed by dose-dependent, HLA class II (DR)-restricted proliferation in response to recombinant and human serum-derived HBcAg and the lack of proliferation to HBV envelope antigens (HBsAg and pre-S(2)Ag). All cloned lines were interleukin 2 dependent, produced interferon-gamma in an antigen-specific manner, and provided antigen-specific help to autologous B cells with respect to anti-HBc production. We conclude that HBcAg-specific, HLA-class II restricted helper T cells capable of inducing antigen-specific functional responses by autologous B lymphocytes and T lymphocytes are present at the site of viral antigen synthesis and hepatocellular injury in HBV infection.

Adult↗
PubMed1986

Clonal analysis of intrahepatic T lymphocytes in chronic active hepatitis. Isolation of a T-cell line specific for hepatitis B core antigen from a patient with serological evidence of exposure to HBV.

We have evaluated whether peripheral blood and hepatic lymphocytes from a patient with chronic active hepatitis (CAH) and antibodies to HBV in serum were specifically sensitized to HBV envelope antigens (HBsAg and pre-S Ag) or to HBcAg. No proliferation to HBV antigens was demonstrated upon stimulation of peripheral blood mononuclear cells either unfractionated or enriched in CD4+ (helper/inducer) T cells. Of 15 T-cell cloned lines (7 CD8+ and 8 CD4+) obtained by limiting dilution in the presence of PHA and recombinant IL2 from liver-infiltrating lymphocytes, one, designated H2, showed specific sensitization to HBcAg, whereas none demonstrated sensitization to viral envelope antigens. The H2 line displayed the CD8+ phenotype, suppressor activity on polyclonal immunoglobulin production and IL2-dependent, HBcAg-specific proliferation. These results suggest that in patients with CAH and serological evidence of previous exposure to HBV, it is possible to obtain lymphocytes specifically sensitized to HBcAg from liver biopsy.

Adult↗
PubMed1986

Selective sensitization of peripheral blood T lymphocytes to hepatitis B core antigen in patients with chronic active hepatitis type B.

The proliferative response of peripheral blood T cells to hepatitis B surface antigen (HBsAg), pre-S antigen and hepatitis B core antigen (HBcAg) has been studied in 20 patients with hepatitis B virus induced chronic active hepatitis (CAH) and in 12 control subjects. Eleven of the 20 CAH patients showed a significant T lymphocyte proliferative response to HBcAg, whereas no proliferation was detectable in response to envelope antigens (HBs and pre-S) in any patient. T cell subset fractionation revealed that HBcAg specific proliferation was limited to the CD4+ (helper/inducer) population. CD8+ (suppressor/cytotoxic) T cells were unresponsive to HBcAg and did not suppress the proliferative response of autologous CD4+ cells. The HBcAg specific T cell proliferative response did not correlate with serum anti-core antibody titres or with biochemical evidence of liver disease. The present results show the selective presence of HBcAg-sensitized T cells in the peripheral blood of patients with HBsAg positive CAH and suggest that the peripheral lymphoid compartment may not reflect immunopathogenetically important cellular events operative at the site of tissue injury.

Adult↗
PubMed1985

Successful treatment of subacute cerebellar degeneration in ovarian carcinoma with plasmapheresis. A case report.

Subacute cerebellar degeneration is a rare complication of some neoplasms, and is generally resistant to therapy. A case of subacute cerebellar degeneration in a 50-year-old woman with a Stage II grade 3 serous ovarian adenocarcinoma is reported. The onset of the neurologic symptoms preceded the diagnosis of cancer and progressively worsened during and after four cycles of chemotherapy. A quick, partial improvement of the neurologic syndrome was documented after three weekly treatments with plasmapheresis. The contribution of circulating factors in inducing subacute cerebellar degeneration can be postulated. A trial using this new type of treatment should be performed in patients who have this therapeutically refractory clinical condition.

Acute Disease↗