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Biomedical subjects

F Bonino

Publications and source records attributed to F Bonino.

At least 181 records · Page 10Linked to original sources
PubMed1987

Natural killer response to exogenous interferon in delta hepatitis: boost or depression defined within the first week of therapy.

Six patients with hepatitis B surface antigen (HBsAg)-positive chronic active liver disease and superimposed delta virus infection were followed up for changes of natural killer (NK) cell function during a 3-month course with median doses of recombinant leukocyte alpha interferon (rIFN). Careful record of the off-therapy NK function means revealed that 3 subjects were boosted, 2 were depressed, and 1 was unchanged. The NK activity patterns showed that after the start of therapy the maximal shift from the off-therapy mean was concentrated in the first week; then the trend, although confirmed, had a gentler slope on the follow-up. This indicated that the first week reflects the availability of rIFN-sensitive NK cells and characterizes the immunological competence of the patient; whilst later in follow-up, suppressive control mechanisms or loss of receptor affinity tend to blur the response. The serum levels of delta RNA dropped in the NK-boosted patients; persistently negative RNA together with clearance of intrahepatic delta antigen was demonstrated solely in that 1 patient showing 164% NK cell function increment in the first week. This study shows that paradoxical responses to exogenous rIFN are not confined to cancer patients, as indicated so far, but may appear in other subjects as well, and reflect the peculiar response of the individual; whenever an NK-dependent clearance of virus-infected cells is required, recognition of the early pattern of reactivity would be useful.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Clinical and epidemiological significance of hepatitis delta virus (HDV) infection in chronic HBV carriers in Portugal.

This study demonstrated that in Portugal HDV infection occurs in 17.3% of HBsAg chronic carriers and chronic HDV infection in 8.4%. As in Northern European countries, HDV infection in Portugal is predominantly found in drug-addicts. Our findings also confirm that HDV infection is associated with an active and progressive liver disease. In delta Ag positive CLD serum HBV-DNA was detected in 10 of 19 cases and was present at low levels. In contrast 52 of 84 delta Ag negative were serum HBV-DNA positive and 48.1% of these had high serum HBV-DNA levels. Ninety per cent of delta Ag positive CLD with serum HBV-DNA positive were drug addicts. These findings indicate that in chronic HDV infection synthesis of HBV is reduced and suggest namely that in drug-addicts their disease derived from the cumulative pathogenic effect of both HBV and HDV. In follow-up biopsy a significantly younger mean age and significantly deterioration of carriers with HDV infection was observed, suggesting that HDV infection accelerates the natural history of HBV related liver disease.

Adolescent↗
PubMed1986

Chronic hepatitis in HBsAg carriers with serum HBV-DNA and anti-HBe.

We compared the clinical and serologic features of 118 hepatitis B surface antigen carriers with hepatitis B e antibody (anti-HBe) followed up for 3-10 yr (mean 6.1 yr), separated according to the presence or absence of hepatitis B virus-deoxyribonucleic acid (HBV-DNA) in serum. The test was performed by molecular hybridization. There were 28 carriers with and 90 without viral DNA. Carriers with serum anti-HBe/HBV-DNA had major liver disease; cirrhosis developed during the follow-up period in 9 of the patients. All had the hepatitis B "core" antigen in the liver, localized prevalently in the cytoplasm of the hepatocytes. Among carriers of anti-HBe alone, 73 had persistently normal tests of liver function and 17 had abnormal levels of alanine transaminase and usually minor forms of liver damage at histology. In a group of 24 carriers of hepatitis B e antigen who spontaneously seroconverted to anti-HBe, hepatitis and a prevalent nuclear distribution of intrahepatic hepatitis B core antigen were found in temporal correlation with the presence of hepatitis B e antigen in serum. The replication of the hepatitis B virion terminated and liver disease remitted after seroconversion to anti-HBe. A positive HBV-DNA test in anti-HBe carriers is associated with a severe and evolutive liver disease and may provide an indication for treatment with drugs inhibiting the synthesis of HBV-DNA.

Adolescent↗
PubMed1986

Treatment of chronic delta hepatitis with alpha-2 recombinant interferon.

The Hepatitis Delta Virus (HDV), a defective ribonucleic acid virus dependent on the Hepatitis B Virus (HBV) is a cause of severe liver disease that often leads to cirrhosis and death. Since the HDV finds in the HBV infection a biological niche in which to thrive indefinitely, the major victims of its infection are the carriers of HBsAg. Spontaneous resolution of chronic HDV hepatitis has been observed rarely and therapeutic attempts with steroids or azathioprine and levamisole have been discouraging. With the advent of recombinant DNA technologies several human alpha-interferons (IFNs) have been synthesized by genetic engineering and the availability of large amounts of the drug has dramatically altered the therapeutic prospects of viral hepatitis. In view of the wide range of biological activities of IFN, including inhibition of viral nucleic acid replication, we have tested the tolerance and the efficacy of this drug in chronic HDV hepatitis. The preliminary results of this study are reported.

Adult↗
PubMed1986

Hepatitis delta virus: protein composition of delta antigen and its hepatitis B virus-derived envelope.

Hepatitis delta virus (HDV)-associated particles were purified from the serum of an experimentally infected chimpanzee by size chromatography and by density centrifugation. Hepatitis delta antigen (HDAg) was detected after mild detergent treatment at a column elution volume corresponding to 36-nm particles and banded at a density of 1.25 g/ml. The serum had an estimated titer of 10(9) to 10(10) HDV-associated particles and had only a 10-fold excess of hepatitis B surface antigen (HBsAg) not associated with HDAg. Therefore, HDV appears to be much more efficiently packed and secreted than is its helper virus, hepatitis B virus (HBV), which is usually accompanied by a 1,000-fold excess of HBsAg. The protein compositions of the HDAg-containing particles were analyzed by immunoblotting with HDAg-, HBsAg-, and hepatitis B core antigen-specific antisera and monoclonal antibodies to HBV surface gene products. The HBsAg envelope of HDAg contained approximately 95% P24/GP27s, 5% GP33/36s, and 1% P39/GP42s proteins. This protein composition was more similar to that of the 22-nm particles of HBsAg than to that of complete HBV. The significant amount of GP33/36s suggests that the HBsAg component of the HDV-associated particle carries the albumin receptor. Two proteins of 27 and 29 kilodaltons which specifically bound antibody to HDAg but not HBV-specific antibodies were detected in the interior of the 36-nm particle. Since these proteins were structural components of HDAg and were most likely coded for by HDV, they were designated P27d and P29d.

Animals↗
PubMed1985

Detection of HBV-DNA by in situ hybridization using a biotin-labeled probe.

A biotin-labeled DNA probe specific for hepatitis B virus (HBV) nucleotide sequences was hybridized in situ to liver tissue of 20 patients; 16 were chronic carriers of hepatitis B surface antigen (HBsAg) and 4 had no markers of HBV infection. HBV-DNA was also analyzed in the serum and the liver of these patients by spot and Southern blot hybridization, respectively. Liver specimens from six carriers were positive for HBV-DNA both by in situ and Southern blot hybridization; ten carriers were negative by in situ hybridization, and two of these were positive by Southern blot technique. The staining was granular, mainly cytoplasmic, limited to liver specimens containing replicative forms of HBV-DNA, and associated with detection of HBcAg in hepatocytes by immunofluorescence. The sensitivity of this technique was not sufficient to detect few copies of integrated HBV-DNA. The hybridization procedure was specific, as results were constantly negative in liver specimens of patients without markers of HBV infection, and no reaction was observed using DNA probes lacking HBV-DNA sequences. Detection of HBV-DNA by in situ hybridization, using a biotinylated probe, is a rapid, reproducible, and specific histochemical method. Currently available biotinylated probes are advantageous when absolute sensitivity is not the limiting factor, and they also facilitate studies of the cellular and subcellular distribution of HBV nucleic acids.

Autoradiography↗
PubMed1985

Familiar clustering and spreading of hepatitis delta virus infection.

The prevalence of hepatitis delta virus (HDV) infection was significantly higher among the relatives of 79 carriers of HBsAg with antibody to HDV (index cases) than among relatives of 111 carriers without serological evidence of HDV infection (controls). Antibody to HDV was found in 45 of the 80 (56%) carriers of HBsAg in families of index cases but only in 2 of 59 (3%) carriers in families of controls (P less than 0.0001). During follow-up new HDV infection developed in 31% of 13 susceptible carriers in families of index cases, but only in 1.2% of 162 susceptible carriers in families of controls (P less than 0.001). None of the family members previously unexposed to the hepatitis B virus had HDV markers in serum or developed this infection during the follow-up. Familial clustering shows that HDV is transmitted by personal contacts, presumably through the inapparent permucosal or percutaneous passage of virus during close or intimate contact. The family model indicates that endemic HDV is maintained and spread through the network of carriers in the community, and that HBsAg carriers in contact with HBsAg/HDV carriers are at high risk of contracting HDV.

Adult↗
PubMed1984

Transmission of the hepatitis B virus-associated delta agent to the eastern woodchuck.

delta agent of human origin was inoculated into four woodchucks chronically infected with woodchuck hepatitis virus (WHV). The animals developed delta infections with serologic patterns similar to those previously observed in human and chimpanzee infections. delta antigen was detected transiently in serum and liver and was followed by seroconversion to anti-delta antibody. Analogous to the chimpanzee model of delta infection, serum and hepatocyte markers of WHV were suppressed in the woodchuck during acute delta infection. The suppression of WHV DNA in serum was evident only during the time of delta-antigen positivity, while the inhibition of other WHV markers was more protracted. The delta antigen in woodchuck sera circulated as an internal component of a particle similar in size to the human delta particle (36-nm diameter) and was encapsidated by the woodchuck hepatitis virus surface antigen; delta antigen from infected woodchuck and chimpanzee livers had similar biophysical properties. Histologic analysis showed that experimental delta infection is associated with a transient acute hepatitis in woodchucks and loss of hepatocytes carrying WHV antigens. The lesions differed from the conspicuous hepatitis associated with reappearance of WHV replication. Hepatitis B-like viruses, therefore, appear to provide the requisite helper functions for delta replication and the woodchuck represents a useful model for study of the virology and pathology of the delta agent.

Animal Diseases↗
PubMed1984

Hepatitis B virus DNA (HBV-DNA) in anti-HBe positive sera.

HBV-DNA measured by the spot hybridization technique, was found in the sera of 28 of 106 (26.4%) anti-HBe positive carriers of HBsAg. Dane particle-associated HBeAg, HBcAg and HBV-specific DNA-polymerase activity were found in the sera of nine (8.5%), five (4.7%) and two (1.9%) of these patients, respectively. All carriers with serum HBV-DNA had chronic liver disease and 18 had intrahepatic delta-Ag and serum anti-delta at titers higher than 1/5000. Intrahepatic HBcAg was detected in the nuclei of 90% of delta negative individuals; 50% of them also had cytoplasmic fluorescence. Only two of the 18 patients with intrahepatic delta-Ag (11%) had HBcAg in the liver. Viral nucleic acid was not found in the sera of 15 other patients with chronic hepatitis, seven of whom had intrahepatic delta-Ag. Serum HBV-DNA was also negative in the remaining 63 symptomless carriers of HBsAg lacking markers of delta infection. Interestingly, although DNA-polymerase negative, some sera gave autoradiographic spots of high optical density. HBV-DNA was detected in them at concentrations typical of sera which are usually both DNA-polymerase and HBeAg positive. Detection of HBV-DNA in serum represents the most direct and sensitive in vitro assay for assessing HBV infectivity and characterizes HBsAg carriers with HBV-related liver damage and ongoing HBV replication independently from the state of HBeAg/anti-HBe system. In the Mediterranean area, the majority of anti-HBe positive carriers with serum HBV-DNA have chronic liver disease and delta infection.

Carrier State↗
PubMed1984

Delta hepatitis agent: structural and antigenic properties of the delta-associated particle.

Delta agent (delta) was serially passaged to a second and third hepatitis B surface antigen (HBsAg) carrier chimpanzee, using as inoculum the peak delta antigen (delta Ag) serum of an animal previously infected with human serum. The characteristics of serially transmitted delta Ag were similar to those described in first-passage animals. It was consistently detected before the development of anti-delta, in association with a 35- to 37-nm subpopulation of HBsAg particles and a unique low-molecular-weight (5.5 X 10(5)) RNA. RNase susceptibility of the delta-associated RNA and release of delta Ag activity upon treatment of delta-associated particles with detergent revealed that this particle is organized into a virion-like form with the RNA and delta Ag as internal components within a coat of HBsAg. Surface determinants of the delta-associated particle other than HBsAg were not detected by radioimmunoprecipitation experiments, using sera of humans and chimpanzees convalescent from delta hepatitis. The HBsAg-associated particle is the "candidate agent" of delta hepatitis.

Animals↗