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Biomedical subjects

F B Hollinger

Publications and source records attributed to F B Hollinger.

At least 91 records · Page 5Linked to original sources

Response to a hepatitis B polypeptide vaccine in micelle form in a young adult population.

Polypeptide micelles with relative molecular weights of 25,000 (p25) and 30,000 (gp30) daltons were prepared from native 22-nm hepatitis B surface antigen (HBsAg) particles. This p25/gp30 complex was alum-adsorbed, and three dosage levels (20 micrograms, 4 micrograms, and 0.8 micrograms) were administered at 0, 1, and 6 months to 51 human volunteers. Local and systemic reactions were clinically insignificant, and all vaccinees seroconverted, regardless of dose. As anticipated, antibody responses diminished as the dosage was reduced. Seroconversion rates and geometric mean antibody levels for the 20 micrograms dosage group were significantly better than those observed with a commercial vaccine and were comparable to those achieved after immunization with 40 micrograms of the intact 22-nm particles used to prepare the polypeptides. By 2 weeks, an anti-HBs response was elicited in 80% of the group receiving 20 micrograms of the polypeptide vaccine. This rapid response to immunization may be particularly beneficial for postexposure prophylaxis where the early development of immunity is advantageous.

Adult↗

Viral hepatitis risk in urban emergency medical services personnel.

Houston has large groups of people known to be at high risk for hepatitis B virus (HBV) infection. Emergency medical services (EMS) personnel are continuously exposed to blood from these high-risk individuals. We sought to determine the prevalence of HBV infection in the city's EMS personnel. Of the 350 Houston firefighters assigned to EMS, 344 were surveyed by questionnaire and a blood specimen was obtained. Each sample was assayed by radio-immunoassay or enzyme-linked immunoassay for hepatitis A antibody (anti-HAV), hepatitis B surface antigen (HBsAg), and antibodies to HBsAg (anti-HBs) and hepatitis B core antigen (anti-HBc). A history of hepatitis was reported by 19 persons, 17 of whom had serologic evidence of infection with HAV (56%), HBV (26%), or both diseases (11%). The anti-HAV prevalence was 16% (12% in whites and 35% in nonwhites; P less than .001). No correlation was observed with years of occupational exposure. Of the 338 personnel evaluated for HBV seromarkers (six HBsAg-vaccinated subjects were excluded), 13% were positive; 0.6% had an active infection as determined by the presence of both HBsAg and anti-HBc; 6.8% were both anti-HBs and anti-HBc positive; 0.9% were positive for anti-HBc alone; and 4.7% of the sera contained only anti-HBs (all with geometric mean antibody levels of less than or equal to 13 mlU/mL). The 28 individuals (8.3%) whose sera contained anti-HBc were classified as cases of previous or concurrent HBV infection. A strong correlation (P less than .004) was observed between HBV infection and years of work exposure in EMS regardless of job description (paramedic versus emergency medical technician).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Extrachromosomal sequences of hepatitis B virus DNA in peripheral blood mononuclear cells of acquired immune deficiency syndrome patients.

The primary etiologic agent of the acquired immune deficiency syndrome (AIDS) is a human T-lymphotropic retrovirus (the AIDS virus). However, the pathogenesis of this virus suggests that other cofactors may contribute to the development of clinically overt disease. The hepatitis B virus (HBV) has been implicated as a potential cofactor because HBV and AIDS virus infections frequently coexist, striking similarities exist in their epidemiologic patterns, and recent data indicate that HBV is lymphotropic. To establish the prevalence of HBV infections in lymphoid cells from individuals with AIDS-related disorders, sera and peripheral blood mononuclear cells (PBMC) from 16 males with AIDS virus infections were examined for the presence of HBV DNA by DNA X DNA blot hybridization. Fifteen (94%) of these individuals had serologic evidence of a recent or prior HBV infection. HBV DNA was detected in the PBMC of all of these patients, regardless of existing HBV serology. Among the 36 control individuals without AIDS-related symptomatology, PBMC-associated HBV DNA was detected in 8 of 14 carriers of hepatitis B surface antigen (HBsAg) and in 3 of 10 individuals immune to HBV, but it was absent from the PBMC of 12 individuals without HBV infection. In all instances, the HBV DNA was extrachromosomal and existed as replicative intermediates or high molecular weight oligomers of the viral genome. Replicative intermediates and serum-associated HBV DNA were detected in all hepatitis B e antigen-positive carriers, regardless of their clinical status. In contrast, the high molecular weight oligomers of HBV DNA were detected in the PBMC of all of the AIDS virus-infected patients examined, but in only 33% of those in the control group who had evidence of HBV infection. This finding suggests that a unique and complex HBV-host-cell interaction exists in patients infected with the AIDS virus.

Acquired Immunodeficiency Syndrome↗

Hepatitis B virus DNA in mononuclear cells and analysis of cell subsets for the presence of replicative intermediates of viral DNA.

To determine whether peripheral blood mononuclear cells (PBMCs) contain replicating forms of hepatitis B virus (HBV) DNA and to define which cell subset may be permissive for viral replication, we analyzed the PBMC DNA from 14 carriers positive for hepatitis B surface antigen (HBsAg) by Southern blot hybridization. HBV-related DNA, which was present exclusively in an extrachromosomal state, was found in the PBMCs of all five hepatitis B e antigen (HBeAg)-positive and three of nine HBeAg-negative carriers. Serum-associated HBV DNA was detected only in those HBsAg carriers whose PBMCs contained HBV DNA forms resembling replicative intermediates (1.0-3.2 kilobase pairs in the EcoRI digests). Analysis of PBMC subsets revealed that replicating forms of the HBV genome were present primarily in monocytes. Low levels of hybridization also were detected in B cells, whereas the T cell fraction (which contained natural killer cells) appeared to be devoid of these replicating forms.

DNA Replication↗

Normal immune response to hepatitis B vaccine in patients with Down's syndrome. A basis for immunization guidelines.

Institutionalized patients with Down's syndrome (DS) are uniquely predisposed to develop chronic hepatitis B infection following exposure. Therefore vaccination is particularly warranted, but there have been concerns that these individuals may react suboptimally. We examined the immune responses of 62 institutionalized patients with DS to 20 and 40 micrograms of hepatitis B vaccine inactivated (Heptavax-B) over one year. The subjects were matched by weight, age, and sex. Seroconversion rates and levels of antibodies to hepatitis B surface antigen (anti-HBs) were comparable to those found in a normal population and were higher than those found in immunocompromised patients undergoing hemodialysis. The anti-HBs levels were consistently higher in the 40-micrograms vaccine group. In patients with DS who were over 30 years old, age was a significant factor in predicting anti-HBs responses. Conversely, in younger subjects, weight was negatively correlated with anti-HBs levels. These data clearly indicate that patients with DS respond normally to hepatitis B surface antigen vaccination and need not be considered a special group when guidelines for vaccination are recommended.

Adolescent↗

Hepatitis B vaccine: immune responses in children from families with an HBsAg carrier.

A 16 microgram dose of HBsAg prepared by the National Institute of Allergy and Infectious Diseases was administered to 71 children, 18 months to 16 years old. The frequency of seroconversion reached 59% (range: 50-78%) at two weeks following the first dose of vaccine and approached 100% one month after the second dose. There were virtually no side effects. Children less than three years of age developed significantly greater anti-HBs responses than did older children or adults. This appears to be related to the greater dose in microgram kg-1 administered to these children. Anti-HBs responses (mIU ml-1) to the vaccine by the Oriental participants were lower at each sampling interval. Our data suggest that prolonging the third dose of vaccine past six months (e.g. to 12 months) may not significantly alter the eventual antibody levels attained by the vaccinees, but may result in suboptimal protection between the second and third dose in some of them.

Adolescent↗

Reduction in risk of hepatitis transmission by heat-treatment of a human Factor VIII concentrate.

A human Factor VIII concentrate containing both a non-A, non-B hepatitis agent and 300 or 30,000 chimpanzee infectious doses of added hepatitis B virus (HBV) was heated to 60 C in the lyophilized state for more than 10 hr. None of the four test chimpanzees that received the heated concentrate developed biochemical or ultrastructural evidence of non-A, non-B hepatitis, whereas both control animals receiving unheated product acquired the disease four to five weeks after infusion. In one of these animals the alanine aminotransferase level remained elevated, a finding indicating unresolved or persistent liver disease. Challenge inoculations with unheated Factor VIII base product (without HBV) resulted in the development of non-A, non-B hepatitis in one of two chimpanzees that previously received the heated product. Hepatitis B infection developed in the control animal that resolved its non-A, non-B hepatitis infection but not in the non-A, non-B hepatitis carrier chimpanzee. Both chimpanzees receiving the heated Factor VIII containing 300 chimpanzee infectious doses of HBV failed to develop hepatitis B until 32 and 40 weeks postinoculation, whereas the two chimpanzees that received heated concentrate containing 30,000 infectious doses of HBV became infected within the expected time. Product characterization and human safety trials have revealed no significant difference between the heated and unheated Factor VIII lots and recovery of product has been exceptionally good.

Alanine Transaminase↗

Localization of hepatitis A virus antigen to specific subcellular fractions of hepatitis-A-infected chimpanzee liver cells.

The localization of hepatitis A virus antigen to specific subcellular fractions of infected chimpanzee liver cells was studied by solid-phase radioimmunoassay following a mild subcellular fractionation procedure designed to separate various organelles from the cytosol and the nuclei. Most of the antigenic activity (93%) was evenly divided between the cytosol fraction and the microsomal suspension. Within the microsomal fraction, more than 75% of the detectable antigen was associated with the smooth endoplasmic reticulum. Less than 4% of the total antigenic activity was localized to the nucleus. These data provide additional evidence that replication of hepatitis A virus occurs primarily within the cytoplasm of the host cell in close association with cellular membranes, consistent with that observed for other members of the genus Enterovirus.

Animals↗

Hepatitis B virus antibody in blood donors and the occurrence of non-A, non-B hepatitis in transfusion recipients. An analysis of the Transfusion-Transmitted Viruses Study.

Patients who received transfusions and nontransfused control patients were followed to assess the incidence and cause of post-transfusion hepatitis and to identify donor factors that might relate to risk of hepatitis. We evaluated as risk factors in donors the presence of antibody to hepatitis B virus compared with elevated alanine aminotransferase (ALT) level. Units of blood that were positive for antibody to hepatitis B core antigen (anti-HBc) were associated with a twofold to threefold greater risk of non-A, non-B hepatitis in the recipients than were units without anti-HBc. In the absence of specific serologic tests for non-A, non-B agents, screening of donors for anti-HBc might be considered. Our data suggest that the incidence of non-A, non-B hepatitis might have been reduced by about one third by such screening. However, elevated ALT levels in donors had a similar association with non-A, non-B hepatitis in recipients but would have resulted in fewer units of blood being discarded than would screening for anti-HBc.

Alanine Transaminase↗

Posttransfusion hepatitis type A.

Hepatitis A virus (HAV) transmission through blood is a rare but potential cause of posttransfusion hepatitis. We can now document such a case supported by laboratory evidence of HAV in the donor blood. A 10-year-old girl manifested icteric hepatitis A 31 days after receiving a single unit of packed RBCs from a donor who subsequently experienced hepatitis A and died in hepatic failure. Hepatitis A virus antigen was detected in the donor's hepatocytes and in plasma obtained from the original donor unit. The density in cesium chloride of the HAV antigenic activity from the liver and plasma ranged from 1.33 to 1.37 g/cu cm, which is similar to that reported for infectious HAV particles. The implicated donor plasma had normal aminotransferase levels and was negative for antibody to HAV. Inoculation of this plasma into a chimpanzee resulted in the development of hepatitis A 23 days later based on the appearance of fecal HAV antigen, hepatitis, and IgM anti-HAV seroconversion. These data clearly document the presence of HAV in the donor sample that produced posttransfusion hepatitis A.

Antibodies, Viral↗

Effect of alkaline glutaraldehyde on hepatitis B virus antigens.

The potential of alkaline 2% glutaraldehyde solutions, with and without surface active agents, to alter the antigenicity of hepatitis B virus (HBV) was analyzed and compared to the antigenic alternation capacities of 0.525% sodium hypochlorite and 2.02% formaldehyde solutions. After treatment of a hepatitis B surface antigen-positive plasma at room temperature for 10 min, there was a 51-67% reduction in surface antigen level and a 90-94% decrease in hepatitis B core antigenicity. Glutaraldehyde is proposed as an alternative to the more noxious hypochlorite and formaldehyde solutions for disinfection of HBV-contaminated articles.

Aldehydes↗

Serum alanine aminotransferase of donors in relation to the risk of non-A,non-B hepatitis in recipients: the transfusion-transmitted viruses study.

To evaluate the incidence of post-transfusion hepatitis and factors influencing its occurrence, the Transfusion-Transmitted Viruses Study prospectively followed 1513 transfusion recipients from 1974 through 1979. The attack rate for non-A,non-B hepatitis was 10 per cent. The incidence of hepatitis was directly related to the alanine aminotransferase (ALT) level in blood donors. In recipients of multiple transfusions of blood that had no donor-ALT level above 29 IU per liter the attack rate was 6 per cent or less; at higher donor-ALT levels the attack rate increased progressively, reaching 45 per cent in recipients of units with an ALT of 60 IU or greater. A similar relation was observed among recipients of single units of blood. Moreover, hepatitis developed in 10 of 11 recipients of two units with an ALT level of 45 IU or greater. These data indicate that screening blood for ALT levels would reduce the incidence of non-A,non-B post-transfusion hepatitis.

Adolescent↗