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Biomedical subjects

G Realdi

Publications and source records attributed to G Realdi.

At least 145 records · Page 8Linked to original sources
PubMed1978

Hepatitis B virus antigens in primary hepatic carcinoma: immunofluorescent techniques on fixed liver tissue.

The presence of hepatitis B surface (HBsAg) and core (HBcAg) antigens was investigated by immunofluorescence in specimens of liver tissue obtained at necrospy in 107 patients with primary hepatic carcinoma. HBsAg was detected in the cytoplasm of liver cells in 16 cases, and in eight of them the antigen was also found in malignant cells. HBcAg, which was present in the nuclei of liver cells in eight cases, was detected in the nuclei of tumour cells in six of these and also in two other cases showing HBsAg, but not HBcAg, in the nonneoplastic tissue. Although most of the primary hepatic carcinomas studied were associated with cirrhotic changes in the non-neoplastic tissue, HBsAg and HBcAg were also detected in the absence of underlying cirrhosis. Hepatitis B virus markers were demonstrated in non-neoplastic tissue, mainly in patients with a well-differentiated carcinoma, and only in these cases were they found also in the neoplastic tissue. These results show that hepatitis B virus antigens, including HBcAg, can be detected in the neoplastic cells of well-differentiated carcinoma of the liver. Although these cells could have been infected after the malignant transformation, a direct oncogenic role of the virus cannot be excluded.

Adolescent↗
PubMed1978

Expression of HBsAg on the membrane of hepatocytes in chronic carriers of hepatitis B virus infection.

Liver cell membrane localization of hepatitis B surface antigen (HBsAg) was investigated in 31 asymptomatic chronic carriers by a direct immunofluorescence technique. A close relationship was found between absence of inflammatory liver disease, presence of large amounts of HBsAg in the liver and expression of the antigen at the hepatocyte surface. Capping of HBsAg after the addition of anti-HBs serum could be inhibited by factors (temperature, metabolic inhibition) that are known to influence viral antigenic mobility at the cell surface. In two patients with chronic active hepatitis as well as in some cases showing histological features of focal parenchymal necrosis, HBsAg could be detected in the cytoplasm of a few scattered hepatocytes but never at the surface of the cells. Both the cases with CAH and one with focal parenchymal necrosis had IgG bound to the liver cell membrane. These findings are in agreement with the hypothesis that the absence of liver damage in HBsAg healthy chronic carriers is related to immune tolerance to the antigen. In chronic active liver disease the presence of IgG on the membrane of hepatocytes suggests a possible role of blocking antibodies directed against viral antigens expressed at the hepatocyte surface.

Adolescent↗
PubMed1978

Antibody dependent cellular cytotoxicity (ADCC) in acute hepatitis B and in chronic active hepatitis.

Antibody-dependent cellular cytotoxicity (ADCC) of peripheral blood lymphocytes against chicken red blood cells (ChRBC) in the presence of specific antiserum has been studied in normal subjects and in patients with acute hepatitis B and with chronic active hepatitis (CAH). ADCC was significantly reduced in patients with acute hepatitis B studied three weeks after the onset of jaundice and in patients with CAH showing clinical, biochemical and histological features of activity. On the other hand, lymphocytes from patients with CAH in histological remission or in clinical and biochemical resolution, showed a significantly increased cytotoxicity. The effect of serum factors on ADCC of normal lymphocytes was investigated using serial serum samples from five patients with acute hepatitis B and five with CAH. Our data suggest that serum factors may be responsible for the impairment of ADCC in our patients, although other mechanisms may also be implied. Sera obtained at the time when ADCC of patients' lymphocytes was reduced, significantly inhibited ADCC of normal lymphocytes when compared with sera obtained at the time when ADCC of patients' lymphocytes was normal or increased. In all cases with CAH, the disappearance or reduction of inhibiting activity correlated with histological remission. In patients with CAH the study of serum factors inhibiting ADCC of normal lymphocytes may be a useful parameter in assessing disease activity.

Acute Disease↗
PubMed1977

[Lymphocytotoxic antibodies and systemic lupus. Clinical correlations and prognostic significance].

The present prospective study was designed to examine the diagnostic and prognostic value of lymphocytotoxins in 20 patients with Systemic Lupus Erythematosus both in active stage and in remission. Lymphocytotoxic antibodies were present in 79% of all the sera examined, in 100% of the sera of patients with active disease and in 52% of those in remission. The different frequency in the two groups is significant as well as the correlation of these antibodies with anti-DNA antibodies, hypocomplementaemia and leukopenia. In spite of their diagnostic value, lymphocytotoxins do not appear as sensible parameter as complementaemia and anti-DNA antibodies in monitoring the disease, since they are still detectable in the sera for several months after the disappearance of clinical signs of activity.

Adolescent↗
PubMed1977

T-lymphocyte cytotoxicity to HBsAg-coated target cells in hepatitis b virus infection.

The cytotoxic effect of peripheral lymphocytes on chicken red blood cells (ChRBC) coated with purified hepatitis B surface antigen (HBsAg) has been studied as an in vitro parameter of cell-mediated immunity in acute and chronic infection with hepatitis B virus. Using this technique, the mean cytotoxic index of lymphocytes from patients with acute hepatitis B (29.13 +/- 20.88) was significantly higher than that obtained with lymphocytes from control subjects (6.53 +/- 3.75). Only 33.3% of the patients with HBsAg-positive chronic active hepatitis exhibited lymphocyte cytotoxicity to HBsAg-coated target cells and the mean cytotoxic index (11.66 +/- 6.60) was in these cases significantly lower than that found in acute hepatitis B. Healthy chronic carriers of HBsAg failed to show lymphocyte cytotoxicity to target cells. The effector cells detected in acute hepatitis B by this in vitro assay have been demonstrated to be T-lymphocytes, as T-cell depleted subpopulations lacked cytotoxic activity. Target cell lysis could be blocked by addition of HBsAg-coated unlabelled ChRBC as well as of purified HBsAg in the culture tubes. It is suggested that damage to the liver cells in acute hepatitis B is related to the presence of cytotoxic T-lymphocytes reacting with HBsAg on the surface of infected hepatocytes. An inadequate lymphocyte response to the antigen may be responsible for the persistence of the infection in the liver with varied clinical manifestations and associated hepatic lesions.

Acute Disease↗
PubMed1976

[Infection due to hepatitis B virus and host immune response].

Cell-mediated immunity (CMI) to hepatitis B surface antigen (HBsAg) was investigated in patients who recovered from acute hepatitis B and in chronic carriers of the antigen, either with or without liver disease. The study was performed using leucocyte migration inhibition test and purified HBsAg. In antigen-negative post-hepatitis patients the frequency of cellular immunity to HBsAg (63.6%) showed a significant difference to controls. On the other hand, only one out of 5 antigen-positive post-hepatitis patients showed sensitisation to HBsAg; four out of these cases had chronic hepatitis at liver biopsy. In HBsAg-chronic carriers, with or without liver disease, the frequency of CMI to HBsAg was not significant to controls. A significant correlation was noted between inflammatory activity and inhibition of migration. Our results suggest that a normal cellular immune response to HBsAg is necessary for the recovery from acute hepatitis B and for the clearance of the virus. In HBsAg-chronic carriers this response seems to be absent or inadequate, leading to the state of healthy chronic carriers or to the evolution to HBsAg-chronic hepatitis, respectively. The high frequency of CMI in HBsAg-negative chronic active hepatitis, suggests that hepatitis B virus infection may play a role in the ethiology of the disease.

Antibodies, Viral↗
PubMed1976

[Liver-specific proteins and autoimmunity in inflammatory liver diseases].

Cell-mediated immunity to a liver specific membrane protein (LP1) has been studied in patients with different types of liver diseases, using the leucocyte migration inhibition test. A high frequency of cellular sensitization to LP1 was detected in untreated chronic active hepatitis, with no significant differences between HBsAg-positive and negative cases. Inhibition of migration is a long-lasting reaction in the spontaneous evolution of the disease, while immunosuppressive treatment normalizes the test only in cases with complete remission. In viral hepatitis B cell-mediated immunity to the liver specific membrane protein can be detected in the acute phase of the disease as a time-limited reaction, exhausted with the clearance of the virus from the liver. An inhibition of migration with LP1 was found also in some cases of HBsAg-positive post-hepatitis patients, in chronic persistant hepatitis, mainly HBsAg-positive, and in asymptomatic chronic carriers of the antigen B. Most of these cases showed a progression to chronic active hepatitis, in clinical and histopathological prospective studies. Our results suggest that cell-mediated immune response to liver specific antigens plays a major role in the pathogenesis of chronic active hepatitis. Moreover the evaluation of these reactions in chronic liver diseases may help in the diagnosis and in the control of the immunosuppressive therapy. Hepatitis B virus infection must be considered one of the possible cause responsible for the rising of autoimmunity to the liver.

Autoantibodies↗
PubMed1976

Liver cell surface localization of hepatitis B antigen and of immunoglobulins in acute and chronic hepatitis and in liver cirrhosis.

This paper describes immunofluorescence studies on liver cell surface localization of hepatitis B surface antigen (HBsAg) and of IgG in acute and chronic hepatitis and in cirrhosis. In acute hepatitis B, HBsAg was found at the surface of hepatocytes in an early phase of the disease, but not during the recovery. This finding is consistent with the hypothesis that immune reactions to HBsAg may be responsible for the liver cell lysis. In HBsAg-positive chronic hepatitis and cirrhosis the antigen was found in the cytoplasm, but not on the surface of the hepatocytes, while in HBsAg-negative cases the antigen could not be detected in the liver cells. Both in HBsAg-positive and in HBsAg-negative chronic active hepatitis (CAH) and cryptogenic cirrhosis IgG bound to the membrane of the hepatocytes could be detected, suggesting a role of antibodies in the pathogenesis of the disease.

Acute Disease↗
PubMed1975

[Frequency of antigen associated to hepatitis due to virus B (HBAg) and of antibody (HBAc) in healthy subjects and during of course of acute and chronic hepatitis. Radioimmunologic study].

Among the several methods employed for the detection of hepatitis B antigen (HBAg) and hepatitis B antibody (HBAb), radioimmunoassay is considered to be the most sensitive and specific. This paper describes a radioimmunoprecipitation test (RIP) for HBAg and HBAb standardized in our laboratory; it consists of a double-antibody precipitation test in a micro-titer system employing 125I-labeled HBAg. The test is compared with double immunodiffusion (ID) and with counterimmunoelectrophoresis (CEP) in the detection of HBAg and HBAb in healthy persons and in patients with acute and chronic liver disease. RIP is 20,000 times more sensitive than ID and 2,500 times than CEP when HBAg is tested, and 40,000 times more sensitive than ID and 10,000 times than CEP for the antibody detection. Moreover the method is reproducible and specific for HBAg and HBAb. With this test the frequency of HBAg in healthy persons was 0% in subjects without any known contact with antigenic material, 0.80% in hospital personnel and 1.17% in high risk personnel (laboratory technicians, blood products workers, ecc.). In acute viral hepatitis the frequency of HBAg was 90% at the admittance to the hospital and 70% at the dimission, while CEP detected a frequency of 85% and 20% respectively. In chronic liver disease the frequency of HBAg with the RIP method was 83.3% in chronic persistent hepatitis, 42.8% in chronic aggressive hepatitis, 23% in cryptogenic cirrhosis and 16.6% in alcoholic cirrhosis. The frequency of HBAb detected with RIP was 4.50% in subjects without any known contact with antigenic material, 6.45% in hospital personnel, 0.41% in high risk personnel, 20% in acute viral hepatitis at the admittance to the hospital and 50% at the discharge, 25% in chronic persistent hepatitis, 14.2% in chronic aggressive hepatitis, 15.3% in cryptogenic cirrhosis and 50% in alcoholic cirrhosis. The high frequency of antibody in healthy persons with no history of hepatitis or parenteral exposure to blood transfusion suggests a widespread diffusion of hepatitis B infection and the possibility of a nonparenteral route transmission. The frequency of HBAg and HBAb in chronic liver disease as detected by a very sensitive method rises the question of a possible role of hepatitis B virus in the pathogenesis of the disease.

Acute Disease↗
PubMedDate not supplied

An antibody which precipitates Dane particles in acute hepatitis type B: relation to receptor sites which bind polymerized human serum albumin on virus particles.

An antibody, which is distinct from the HBsAg- reacts with antigenic sites on Dane particles- HBcAg and HBeAg, was studied by radioimmunoprecipitation of radioactive intact hepatitis B virions in sera obtained early in the course of acute hepatitis type B. The antibody, previously termed anti-Dane particle (anti-DP) antibody, was reactive with Dane particles and HBsAg particles obtained from HBeAg-positive sera but not with HBsAg particles from anti-HBe containing sera. The expression on virus particles of the evoking antigen correlated with levels of binding sites for polymerized human serum albumin (pHSA) as detected by solid-phase radioimmunoassay. In acute hepatitis B sera, levels of anti-DP antibody activity showed inverse correlation with expression of pHSA receptors on circulating virus particles, although the two reactivities were not mutually exclusive. In inhibition experiments, pHSA blocked precipitation of Dane particles by anti-DP positive sera, while native human albumin and polymerized bovine albumin had no effect. The inhibition by pHSA of the anti-DP reaction appeared specific since identical concentrations of pHSA did not interfere with precipitation of virus particles by anti-HBs. Affinity chromatography studies with anti-DP insolubilized on Sepharose 4B columns showed selective binding to the gel of radioactive Dane particles; 125I-HBsAg was not reactive. The binding of Dane particles to anti-DP columns was completely inhibited when virus particles were applied to the gel in pHSA; pretreatment of the column with pHSA did not affect the reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Centrifugation, Density Gradient↗
PubMedDate not supplied

Clinical, virologic and histologic outcome following seroconversion from HBeAg to anti-HBe in chronic hepatitis type B.

Seventy consecutive HBsAg- and HBeAg-positive patients with biopsy-proven chronic hepatitis were followed prospectively with serial determinations of SGPT levels and hepatitis B virus serum markers including HBsAg, HBeAg, anti-HBe and hepatitis B virus DNA. During a period of 1 to 11 years (mean +/- S.D.: 5.0 +/- 2.3 years), 28 patients remained persistently HBeAg positive, most with continuing biochemical and histologic activity, while 41 cases seroconverted to anti-HBe. One patient became HBeAg and anti-HBe negative. After seroconversion, 87.8% of the cases showed sustained normalization of SGPT, and clearance of hepatitis B virus DNA from serum and histologic improvement was documented in 79% of the cases who had a control liver biopsy, while 15.8% developed cirrhosis. In two patients (4.9%), the disease remained active despite seroconversion, and both cases had evidence of continuing hepatitis B virus replication. Finally, reactivation of liver damage and of hepatitis B virus replication was observed in three additional patients (7.3%) who had transiently normalized SGPT after seroconversion. All 70 patients were analyzed for hepatitis delta virus markers, and only two persistently HBeAg-positive cases were found positive for antibody to hepatitis delta virus in serum, one also having hepatitis delta antigen in the liver. These findings indicate that, in chronic hepatitis type B, termination of virus replication is associated in most patients with biochemical and histologic regression of inflammatory activity. After anti-HBe seroconversion has occurred, virus replication and liver disease may persist or reactivate in a small proportion of patients thus giving origin to the well-recognized group of anti-HBe positive, hepatitis B virus DNA-positive chronic hepatitis type B.

Adolescent↗
PubMedDate not supplied

Differential distribution of hepatitis B core and E antigens in hepatocytes: analysis by monoclonal antibodies.

Current knowledge on the expression of HBeAg in hepatocytes is incomplete because of difficulties in obtaining monospecific antisera devoid of anti-HBc reactivity. In this study, we have examined by immunofluorescence the expression of HBcAg and HBeAg in cryostat liver sections from 25 chronic carriers of HBsAg using monoclonal antibodies. Although virtually all liver biopsies displayed concordance for HBeAg and HBcAg expression, the pattern of fluorescence differed markedly. Thus, monoclonal anti-HBc gave nuclear staining in all 13 reactive biopsies, while cytoplasmic staining was observed in only two of these. In contrast, monoclonal anti-HBe showed cytoplasmic reactivity coexisting with nuclear reactivity in 10 of 13 reactive biopsies. Hepatitis B virus DNA polymerase activity in the serum appeared to correlate better with the presence of HBcAg in hepatocytes rather than HBeAg. These results provide further evidence that HBeAg is expressed both in the nuclei and in the cytoplasm of infected hepatocytes. The observation that the number of cells expressing HBeAg exceeds those expressing HBcAg in carriers with active virus replication would suggest that assembly of core particles occurs in only a proportion of infected hepatocytes expressing HBeAg.

Antibodies, Monoclonal↗