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Biomedical subjects

A F Bradburne

Publications and source records attributed to A F Bradburne.

At least 19 recordsLinked to original sources

An electron microscope study of three-component immune complexes.

Immune electron microscopy has been used to examine the appearance of three-component complexes. The three components are antigen, supplied by two dissimilar viruses, antibody, and a secondary immune reactant. Secondary reagents used in the study are antispecies immunoglobulin (anti-IgG), rheumatoid factor (RF), and complement. Each of these secondary reagents produced cross-linking between antigenically unrelated immune complexes, and it was found possible to distinguish visually the mixed complexes produced by each of them. The significance of the appearance of these mixed complexes is discussed and related to the neutralisation enhancement that can occur in the presence of secondary immune reactants. The appearance of the complexes is also related to the false positive results that can be obtained in carrying out solid phase immunoassays.

Antibodies, Anti-Idiotypic↗

Enzyme-linked immunosorbent assay for the detection of human rotavirus in stools.

A simple method for the detection of human rotavirus in stools is described, using a double antibody sandwich enzyme-linked immunosorbent assay. Polysterene microtitre plates were used as solid phase. Four capture antibodies were tried, bovine, egg-derived, guinea pig and monoclonal antibody to rotavirus. Both bovine and egg-derived antirotavirus labelled with horseradish peroxidase were used as the detecting antibodies. The results obtained were compared with a commercially available ELISA, Rotazyme (Abbott Laboratories), and also with the direct detection of rotavirus by electron microscopy. Bovine antibody was found to be an unsuitable capture antibody due to non-specific false positive reactions.

Animals↗

The effect of sodium thiocyanate on virus structure.

A study of two different virus types after elution from immunosorbent columns by sodium thiocyanate has shown that virus degradation occurs. The two virus types studied were hepatitis B and rotavirus. Hepatitis B antigen (HBAg) was only slowly degraded and retained many of its morphological features, although in an altered form; rotavirus was highly sensitive to the chaotropic agent, losing both its viability and its morphological integrity. During the process of disassembly a previously undetected inner component of rotavirus could be visualised, which was termed the "core."

Capsid↗

Hepatitis B virus infection in southern African blacks with hepatocellular cancer.

The association between hepatitis B virus (HBV) infection and hepatocellular cancer (HCC) in southern African blacks was investigated by examination of patients' sera for all the currently known markers of HBV. Hepatitis B surface antigen (HBsAg) was present in the sera of 61.6% (178/289) of the patients compared with only 11.3% (24/213) of age-matched, sex-matched, and ethnically matched controls (P less than 0.001). Antibody against HBsAg was found in 17% of the patients and 41.7% of the controls (P less than 0.001). In 74 patients studied in more detail, antibody against the hepatitis B core antigen (anti-HBc) was detected in 89%, almost always in high or moderately high titer. Anti-HBc was found in 37.5% of the controls. Active HBV infection, as indicated by positive tests for HBsAg or anti-HBc, was present in 91% of the patients compared with 39.4% of the controls (P less than 0.001). Hepatitis B e-antigen was detected in 2.3% and its specific antibody in 20.5% of the patients. The corresponding figures in the controls were 0 and 55%. HBs antigenemia was more common in younger patients with HCC. No relationship was demonstrated between alpha-fetoprotein and HBs antigenemia. HBV infection was equally common in patients with and without cirrhosis in the nontumorous liver.

Adult↗

A solid-phase system (SPACE) for the detection and quantification of rotavirus in faeces.

This report describes the development of a solid-phase haemadsorption system using chromic chloride-linked, antibody coated erythrocytes. It is proposed to call this technique solid phase aggregation of coupled erythrocytes (SPACE). The system is suitable for the detection of virus antigens, such as from rotavirus infections, which are present in 'dirty' or 'mixed' preparations such as faeces, urine or exudates. The test uses microtitre U-form plates coated with specific antivirus antibody; faecal suspensions are added and virus or antigen allowed to adsorb. The plates are then washed and adsorbed antigens are detected by the addition of virus-specific IgG-coated erythrocytes. The resultant settling pattern is read in the same manner as a conventional haemagglutination test. The system is compared with electron microscopy and fluorescent antibody techniques.

Animals↗

Hepatitis B core antigen immune complexes in the liver of hepatitis B patients.

Single liver biopsies from 102 clinically diagnosed hepatitis patients were examined by immunofluorescence for the presence of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg), complement and immunoglobulin deposition, and for their capacity to fix human complement in vitro. Of the sixty-five HBsAg positive livers, fifty-three were histologically diagnosed as chronic hepatitis, three as acute hepatitis, five as acute hepatitis with signs of transition to chronicity, and four as 'near normal liver'. In the group with chronic hepatitis, HGcAg was observed in thirty-nine livers, all of which also had HBsAg. Thirty-five of these thirty-nine cases also had the ability to fix complement in vitro in the hepatocyte nuclei and/or cytoplasm. Of these thirty-five cases, twenty-nine were positive for immunoglobulin deposition on the nuclei. All of these cases had antibody to HBcAg in the blood, but only five had anti-HBs. The frequency of in vitro complement fixation and immunoglobulin deposition was higher in active forms of the disease, such as chronic aggressive hepatitis and active cirrhosis, than in non-active disease such as chronic persistent hepatitis and mild cirrhosis. By the application of double fluorescent staining techniques, complement fixation was observed in some HBcAg-positive nuclei. In the 'near normal liver' cases there was no intrahepatic accumulation of HBcAg, and despite the presence of anti-HBc in the blood, in vitro complement fixation and immunoglobulin deposition were both absent. The group of three HBsAg ositive 'acute hepatitis with signs of transition to chronicity' cases behaved similarly to those with chronic aggressive hepatitis and had circulating anti-HBc, in vitro complement fixation and immunoglobulin deposition in the hepatocytes. None had circulating anti-HBs. In the group sith HBs-positive acute hepatitis, anti-HGc in the blood was the only other evidence of hepatitis B virus infection.

Antigen-Antibody Complex↗

Administration of human fibroblast interferon in chronic hepatitis-B infection.

One patient with hepatitis-B surface antigen (HBsAg)-positive chronic aggressive hepatitis, and two chimpanzee carriers of HBsAg, were each given seven doses of 10(7) I.U. of human fibroblast interferon over two weeks. The main differnce observed after treatment was a depression of the nucleocapsid hepatitis-0 core antigen in the liver, indicating that hepatitis-B virus infection is sensitive to interferon. Except for a short febrile reaction, no undesirable effects were seen after the administration of human fibroblast interferon which has not been previously given to man.

Adult↗

Transmission of hepatitis type B from healthy HBsAg-positive mothers.

Seventeen mothers, all apparently healthy carriers of hepatitis-B surface antigen (HBsAg) during pregnancy, and their children were studied for four to five years to determine the transmission rate of hepatitis-B virus infection. All the mothers had antibody against hepatitis-B core antigen in addition to HBsAg. One of them, a renal transplant recipient, was persistently positive for hepatitis-B-associated e antigen (HBeAg), while the remaining 16, who were detected during screening of healthy pregnant women were positive for anti-HBe. Evidence of infection was found in the child and husband of the woman positive for HBeAg, while none of the 29 children and five husbands of the anti-HBe-positive women became infected.

Antibodies, Viral↗

Hepatitis B surface antigen (HBsAg) in the liver of patients with hepatitis; a comparison with serological detection.

Chronic hepatitis was diagnosed on liver biopsy of 76 patients; 52 (68%)had HBsAg. Of the 52 patients with HBsAg, 23% had HBsAg shown by immunofluorescence on the liver, while it could not be detected with radioimmunoassay on the serum; 77% had HBsAg detectable in liver and in serum, and none had HBsAg in serum only. HBsAg was detected more frequently in chronic aggressive hepatitis and active cirrhosis than in chronic persistent hepatitis and cirrhosis with little activity. No correlation was found in the different forms of chronic hepatitis between the HBsAg status on the one hand, and levels of transaminases, gammaglobulins, and auto-antibodies on the other. Acute hepatitis was diagnosed on liver biopsy of 24 patients; 50% had HBsAg. Liver tissue positivity was very low in the fully developed stage compared to serum positivity. In 146 patients with other liver ailments, both liver and serum were negative for HBsAg.

Acute Disease↗

Distribution patterns of hepatitis B surface antigen (HBsAg) in the liver of hepatitis patients.

One hundred liver biopsies from 100 hepatitis patients were examined by the indirect immunofluorescent technique for the detection of HBsAg. Of the 60 positive specimens 52 were diagnosed as various types of chronic hepatitis and 8 were acute hepatitis. Four main distribution patterns of HBsAg were obtained: full cytoplasmic fluorescence with diffuse lobular distribution; cytoplasmic fluorescence with spotty distribution; peripheral fluorescence in the cell membrane and/or cell peripheries; and focal cytoplasmic positivity. There was an inverse relationship between the number of positive hepatocytes and the extent of liver cell necrosis. The distribution patterns of HBsAg were distinctive in each type of chronic hepatitis and in acute hepatitis. Homogeneous full cytoplasmic fluorescence, distributed diffusely in the whole liver lobule, was observed in chronic persistent hepatitis and in cirrhosis with little activity whereas peripheral liver cell membrane and/or peripheral cytoplasmic fluorescence associated with cytoplasmic positivity in a smaller number of hepatocytes was a characteristic finding in chronic aggressive hepatitis, active cirrhosis, and acute hepatitis with possible transition to chronicity. Focal cytoplasmic fluorescence was observed in acute hepatitis and a group of biopsies in chronic hepatitis in which HBsAg was detected in the liver but no antigen was detectable in the serum. The results show that the different patterns of distribution of HBsAg in the liver biopsy are helpful for the histological diagnosis of different types of HBAg positive viral hepatitis and are consistent with the hypothesis of the role of specific immune response in the pathogenesis of type B viral hepatitis.

Acute Disease↗

Differential distribution of hepatitis B surface antigen and hepatitis B core antigen in the liver of hepatitis B patients.

One hundred liver biopsies from 100 patients with clinical presumptive diagnosis of hepatitis were examined by immunofluorescence for the presence of hepatitis B surface antigen (HBSAg) and hepatitis B core antigen (HBcAg). Of the 60 HBsAg-positive livers, 51 were diagnosed as chronic hepatitis on histological grounds, 6 as acute hepatitis, and 3 as "near-normal liver." From the 60 tissue-positive cases, 3 subjects were HBsAg seronegative. HBcAg was detected in 44 livers, all of which also had HBcAg in the localized in the cytoplasm and the membranes of the hepatocytes, and HBcAg in the nuclei and in 4 cases also in the cytoplasm. Predominant HBsAg expression in the cytoplasm was observed in near-normal liver, chronic persistent hepatitis, and cirrhosis with little activity. This correlated with the amount of ground glass hepatocytes in the biopsies. HBcAg and membrane-localized HBsAg were minimal in those conditions. HBcAg was most prevalent in patients with chronic aggressive hepatitis and active cirrhosis treated with immunosuppressive drugs, whereas the amounts of HBsAg and HBcAg in nontreated patients of those two groups and in acute hepatitis with signs of transition to chronicity were almost equal. HBsAg expression in liver cell membranes was most prominent in active forms of chronic hepatitis (chronic aggressive hepatitis and in active cirrhosis) and in acute hepatitis with signs of transition to chronicity. This observation correlated in the presence of HBcAg in the biopsies of those patients. In acute hepatitis both HBsAg and HBcAg were detected rarely and no membrane expression of HBsAg was observed. The over-all results show a significant relationship between the different degrees of accumulation of HBsAg and HBcAg in the liver and the various histological types of hepatitis and further suggest an interplay of both hepatitis B virus and host immune response in the development and pathogenesis of hepatitis B.

Acute Disease↗

Hepatitis-B immunoglobulin in prevention of HBs antigenaemia in haemodialysis patients.

In a double-blind study, hepatitis-B immunoglobulin significantly protected patients in a haemodialysis unit against the development of HBs antigenaemia, compared to control patients receiving normal human immunoglobulin (p less than 0-01). Injections were given at the beginning and after 6 months, and observations extended over 16 months. Analysis of antiHBc and anti-HBs antibodies suggested that neutralisation of the virus inoculum, as well as modification of infection, may be implicated in the prevention of HBs antigenaemia.

Adult↗

Core antibodies and other parameters of hepatitis B virus infection in a tropical population.

HBsAg (80% of ay subtype) was detected with radioimmunoassay in 10% of a sample of the healthy population in Mopti, Mali, and in 6% with counterelectrophoresis. Anti-HBs was detected in approximately 57% of adults, and anti-HBc in 50%. Anti-HBs was not always detectable in anti-HBc positive sera with the methods used, and vice versa. This accounted for up to 85% of an adult group showing anti-HBs, anti-HBc, or both. While anti-HBc percentages climbed more gradually with age, and 'adult' percentage of anti-HBs was reached at about 3 years of age, and there were no significant differences in the age distribution of HBsAg.

Adolescent↗

Coronative antibody tires in sera of healthy adults and experimentally infected volunteers.

Six coronaviruses isolated in the U.S.A. have been inoculated into volunteers and all produced colds. Between 10 and 20% of infected volunteers developed heterologous antibody responses after these and other experimental infections with coronaviruses. The haemagglutination-inhibition test with the OC43 virus strain was found to detect antibody rises after infection with a variety of strains.Studies on normal adult sera taken between 1965 and 1970 revealed a high frequency of neutralizing antibody to one strain (229 E) and a frequency of HI antibody to strain OC43 which fluctuated from year to year. Complement-fixing antibodies to these two viruses were also found, revealing an apparent increase in the activity of coronaviruses in the general population of the U.K., during the winter of 1968-9.

Antibodies↗

Studies of respiratory viruses in personnel at an Antarctic base.

Thirteen men wintering on an Antarctic base were isolated from other human contact for 10 months. During this period Coxsackievirus A21 and later influenza A2 virus were administered to some of the men. Serum samples were collected from each of the men at monthly intervals.Coxsackievirus A21 produced symptoms and apparently spread to uninoculated men. It also appears that repeated re-infections occurred and that the virus persisted in this small community for most of the period of isolation. HI antibody responses in the absence of neutralizing antibody responses seem to be transient.The vaccine strain of influenza virus induced antibody responses but did not cause symptoms. There was no evidence of spread to uninoculated men.Antibody titres against influenza C, parainfluenzaviruses 1 and 2 and coronavirus OC43 did not fall significantly during isolation.An outbreak of respiratory illness occurred at the end of isolation and its origin was traced. No causative agent was detected.

Antarctic Regions↗