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Biomedical subjects

F B Hollinger

Publications and source records attributed to F B Hollinger.

At least 19 recordsLinked to original sources
PubMed1992

Long-term mortality after transfusion-associated non-A, non-B hepatitis. The National Heart, Lung, and Blood Institute Study Group.

BACKGROUND: Acute non-A, non-B hepatitis after blood transfusion often progresses to chronic hepatitis and sometimes culminates in cirrhosis or even hepatocellular carcinoma. However, the frequency of these sequelae and their effects on mortality are not known. METHODS: We traced patients with transfusion-related non-A, non-B hepatitis who had been identified in five major prospective studies conducted in the United States between 1967 and 1980. We matched each patient with two control subjects (identified as the first and second controls) who received transfusions but who did not have hepatitis. The mortality rates in the three groups were determined with use of data from the National Death Index and Social Security Death Tapes. Cause-specific mortality was determined by reviewing death certificates. RESULTS: Vital status was established for over 94 percent of the 568 patients who had had non-A, non-B hepatitis and the two control groups (526 first controls and 458 second controls). After an average follow-up of 18 years, the estimate by life-table analysis of mortality from all causes was 51 percent for those with transfusion-associated non-A, non-B hepatitis, as compared with 52 percent for the first controls and 50 percent for the second controls. The survival curves for the three groups were virtually the same. Mortality related to liver disease was 3.3, 1.1, and 2.0 percent, respectively, among the three groups (P = 0.033 for the comparison of the group with non-A, non-B hepatitis with the combined control group). Seventy-one percent of the deaths related to liver disease occurred among patients with chronic alcoholism. CONCLUSIONS: In this long-term follow-up study, there was no increase in mortality from all causes after transfusion-associated non-A, non-B hepatitis, although there was a small but statistically significant increase in the number of deaths related to liver disease.

Alcoholism↗
PubMed1992

Polymerase chain reaction assay for hepatitis C virus RNA using a single tube for reverse transcription and serial rounds of amplification with nested primer pairs.

A procedure is described for the detection of hepatitis C virus (HCV) RNA in blood by means of the polymerase chain reaction (PCR) in which the reverse transcription step and two rounds of amplification are carried out in a single tube. This results in fewer manipulations, reduced risk of contamination, and economy of time. The procedures are generally applicable to other assays based on the PCR. We describe the preparation (from 100 microL serum) of test samples that remain stable for at least 6 days under specified conditions and an assay that employs nested primer pairs homologous to conserved sequences in the 5' noncoding region. The method was tested on 107 sera from the United States and Japan. Correlation with first-generation anti-HCV was 77%. Two sets of nested primer pairs homologous to sequences in the 5' noncoding region and one set based on structural region sequences showed differences in their reactivities with serum HCV RNA. The recommended single tube procedure specified a primer for reverse transcription that was conserved in all reported HCV genomes but absent from pestivirus genomic sequences. The effects of preanalytical factors on the detection of HCV RNA were studied. Qualitatively, there was no change in the HCV RNA-positivity of sera that were exposed to room temperature for 24 hours. Quantitative studies showed a decrease in titer in some specimens. Three cycles of freeze-thawing had no detectable effects on the titers of HCV RNA.

Base Sequence↗
PubMed1992

Simultaneous detection of HBV-specific antigens and DNA in paraffin-embedded liver tissue by immunohistochemistry and in situ hybridization using a digoxigenin-labeled probe.

To understand the pathogenesis of HBV infection at the single cell level, we have established a sensitive, specific and reproducible method for the simultaneous in situ detection of HBV-specific nucleotide sequences and antigens in paraffin-embedded liver tissue using nonradioactive hybridization and immunohistochemical techniques. Liver sections were stained for HBsAg or HBcAg by immunohistochemistry (IHC) using an enhanced biotinstreptavidin technique. Following immunohistochemical staining of the liver sections, in situ hybridization (ISH) was performed on the same section using a digoxigenin-labeled, HBV-specific probe. Specific hybridization was detected using an anti-digoxigenin, Fab fragment-alkaline phosphatase conjugate. This simultaneous assay permits the subcellular localization of HBV DNA and antigens with excellent preservation of tissue morphology and absence of background staining. In addition, the types and percentage of cells harboring HBV in the tissue can be determined. Although both reactions are detected by immunohistochemical methods, the application of a dual detection system using two different color reagents permits the identification of HBV antigens as a red signal and HBV DNA as a blue-purple signal at the single cell level. Both ISH and IHC can be performed in the same tissue section without significantly reducing the sensitivity of either assay. In addition, since this simultaneous detection assay can be completed within two days and eliminates the need for radioactive probes, it may be used effectively as a routine clinical procedure.

DNA Probes↗
PubMed1992

Standardization of sensitive human immunodeficiency virus coculture procedures and establishment of a multicenter quality assurance program for the AIDS Clinical Trials Group. The NIH/NIAID/DAIDS/ACTG Virology Laboratories.

An independent quality assurance program has been established by the Division of AIDS, National Institute of Allergy and Infectious Diseases, for monitoring virologic assays performed by nearly 40 laboratories participating in multicenter clinical trials in the United States. Since virologic endpoints are important in evaluating the timing and efficacy of therapeutic interventions, it is imperative that virologic measurements be accurate and uniform. When the quality assurance program was initially created, fewer than 40% of the laboratories could consistently recover human immunodeficiency virus (HIV) from peripheral blood mononuclear cells (PBMCs) of HIV-infected patients. By comparing coculture procedures in the more competent laboratories with those in laboratories who were struggling to isolate virus, optimal conditions were established and nonessential reagents and practices were eliminated. Changes were rapidly introduced into a laboratory when experience dictated that such modifications would result in a favorable outcome. Isolation of HIV was enhanced by optimizing the numbers and ratios of patient and donor cells used in cultures, by standardizing PBMC separation procedures, by using fresh rather than frozen donor PBMCs, by processing whole blood within 24 h, and by using natural delectinated interleukin 2 instead of recombinant interleukin 2 products in existence at that time. Delays of more than 8 h in the addition of phytohemagglutinin-stimulated donor cells to freshly separated patient PBMCs reduced recovery. Phytohemagglutinin in cocultures and the addition of Polybrene and anti-human alpha interferon to media were not important in HIV isolation. The introduction of a consensus protocol based on this information brought most laboratories quickly into compliance. In addition, monthly monitoring has successfully maintained proficiency among the laboratories, a process that is critical for the scientific integrity of collaborative multicenter trials. Problems which might not be appreciated for months are now being resolved early, before data can be compromised unknowingly. This consensus protocol is recommended for any laboratory attempting to isolate HIV for the purpose of standardizing recovery and for accessing virologic endpoints in clinical trials.

Culture Media↗
PubMed1992

Frequency of dual infections of corneas with HIV-1 and HHV-6.

In the current study, 35 pairs of corneas from asymptomatic carriers of HIV-1 and ten pairs from AIDS patients were analyzed for the presence of HIV-1 and HHV-6. The tissues were evaluated for viral antigens, transcripts, DNA sequences and intact and infectious virus. Three corneas from two asymptomatic carriers of HIV-1 and three corneas from two AIDS patients were culture positive for HIV-1. One of the three HIV-1 positive corneas from an asymptomatic HIV-1 carrier also was culture positive for HHV-6. Two of the tissue culture positive corneas from asymptomatic HIV-1 carriers and two from AIDS patients also tested positive for HIV-1 transcriptional activity by in situ hybridization. The label denoting the transcriptional activity was limited to stromal keratocytes. Most significantly, we were able to demonstrate the presence of HIV-1 particle(s) in sections and cultured PBMC from one of the HIV-1 culture positive corneas. PBMC from the same cornea also contained herpes virus particles. This report strengthens our earlier findings that HIV-1 and HHV-6 can invade corneal tissue, which emphasizes the importance of vigorous screening of corneal donors, specifically donors with HIV-1 exposure.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Transcriptional activity of HIV-1 and HHV-6 in retinal lesions from AIDS patients.

This study determined the frequency of multiple viral (HIV-1, HHV-6, and CMV) infections in 26 retinas from 16 AIDS patients. Of the 12 retinas of 26 that tested positive for HIV-1 DNA sequences, seven also were positive for HHV-6 DNA sequences. Four of these seven retinas were culture positive for HIV-1 and two of the four contained CMV DNA sequences and antigens. Using RNA probes, HIV-1 and HHV-6 transcriptional activity was demonstrated in two of the four HIV-1 culture positive retinas. These retinas also contained CMV DNA sequences and antigens. The results demonstrate that more than 35% of AIDS patients suffer from at least two simultaneous viral infections and 15% suffer from three viral infections. The presence of transcriptional activity of HIV-1 and HHV-6 suggests an active infection.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Bleeding from a Meckel's diverticulum after the use of ibuprofen.

A Meckel's diverticulum is an unusual site of gastrointestinal bleeding in adults. Bleeding often results from ulceration of ileal mucosa that lies adjacent to ectopic gastric mucosa. We report on a 27-yr-old man who bled from a Meckel's diverticulum after receiving oral ibuprofen, a nonsteroidal antiinflammatory drug. Examination of the resected diverticulum revealed fundal-type gastric mucosa with inflammation, submucosal hemorrhages, erosions and ulceration in the absence of Helicobacter pylori. The ileal mucosa was spared in this patient. These features suggest that oral ibuprofen caused damage to the ectopic gastric mucosa, precipitating significant hemorrhage. This is the first report in the English literature of such an occurrence.

Adult↗
PubMed1991

Hepatitis C virus infection in post-transfusion hepatitis. An analysis with first- and second-generation assays.

BACKGROUND: The causes of post-transfusion non-A, non-B hepatitis are still not fully defined, nor is it clear how accurate the tests are that are used to screen blood donors for hepatitis C virus (HCV) and to diagnose post-transfusion hepatitis caused by infected blood. METHODS: We used two first-generation enzyme-linked immunoassays (EIAs) and one second-generation immunoassay to test for anti-HCV antibodies in serum samples collected between 1976 and 1979 in the Transfusion-Transmitted Viruses Study (from 1247 patients who underwent transfusion and 1235 matched control subjects who did not receive transfusions). We tested serum collected before and after infection from the patients in whom non-A, non-B hepatitis developed, serum from their blood donors, and serum from 41 of the control subjects who had hepatitis unrelated to transfusion. RESULTS: Of the 115 patients in whom post-transfusion non-A, non-B hepatitis developed, the initial serum samples of 111 were anti-HCV-negative; after hepatitis developed in these 111 patients, the first-generation EIAs detected anti-HCV in 51 (46 percent), and the second-generation assay detected anti-HCV in an additional 16 (14 percent), for a total of 60 percent. Of 40 controls, 37 were anti-HCV-negative initially, and none seroconverted after hepatitis developed. If the 3 percent rate of non-A, non-B, non-C hepatitis among the controls (37 of 1235) was applied to the 1247 transfusion recipients, only 74 of the 111 cases of hepatitis were attributable to the transfusion. Thus, 91 percent (67 of 74) of the cases of post-transfusion hepatitis were caused by HCV. Of the 99 donors, 60 were HCV-positive (9 on second-generation tests only) and 39 were not. CONCLUSIONS: Nearly all cases of non-A, non-B post-transfusion hepatitis are caused by HCV. Screening with a second-generation assay improves the rate of detection of HCV infection in patients with post-transfusion hepatitis and in blood donors. The use of this test showed a 3.6 percent risk of non-A, non-B, non-C hepatitis, which was not significantly different from the rate in the controls (3.0 percent).

Blood Donors↗
PubMed1991

The incidence of HIV-1 and HHV-6 in corneal buttons.

Twenty pairs of corneas from asymptomatic carriers of HIV-1 and seven pairs from AIDS patients were analyzed for the presence of HIV-1 and HHV-6 antigens, viral transcripts, DNA sequences, and intact and infectious particles. Although serum from all donors was positive for both HIV-1 and HHV-6 antibody by Western blot analysis, only one cornea from an asymptomatic carrier of HIV-1 was positive for HIV-1 and HHV-6. The cornea was positive when tested by tissue culture, PCR, in situ hybridization, and electron microscopy. There was no tear film contamination. These results suggest that HIV-1 and HHV-6 may be capable of invading corneal tissue.

Acquired Immunodeficiency Syndrome↗
PubMed1990

A multicenter clinical trial of oral ribavirin in HIV-infected people with lymphadenopathy: virologic observations. Ribavirin-LAS Collaborative Group.

A double-blind, randomized, placebo-controlled trial comparing two daily doses of oral ribavirin (600 and 800 mg) and a placebo was performed at four medical centers geographically distributed throughout the USA. One hundred and sixty-four HIV-infected adult men with lymphadenopathy were enrolled over a 2-month period and received active treatment for 24 weeks followed by a 4-week interval during which they did not receive the study drug. A marked interlaboratory variation in HIV isolation from peripheral blood mononuclear cells was observed, underscoring the critical role of quality assurance in similar multicenter trials. Nevertheless, the combined data indicate that ribavirin did not significantly suppress HIV activity (on measurement of reverse transcriptase activity) after week 6 or reduce serum p24 antigenemia.

AIDS-Related Complex↗
PubMed1978

Cellular and humoral immunity in guinea pigs to two major polypeptides derived from hepatitis B surface antigen.

Guinea pigs immunized with hepatitis B surface antigen (HBsAg), types adw, adr and ayw, and with two major polypeptides derived from HBsAg/adw developed cell-mediated immunity as determined by the macrophage migration inhibition assay. Peritoneal exudate cells from animals immunized with a 22000- or a 25000-mol. wt. polypeptide derived from HBsAg/adw showed significant migration inhibition after challenge with either polypeptide or with purified HBsAg. Significant inhibition of macrophage migration was not observed when polypeptide-sensitized cells were challenged with normal human serum or with normal human liver extract. Similarly, a cell-mediated immune response was not observed in peritoneal exudate cells from animals sensitized to normal human serum or normal human liver extract which were challenged with either of the polypeptides. The humoral immune response to either of the polypeptides, as measured by radioimmunoassay, was substantially lower than that observed in animals immunized with intact particles. This apparent difference between cellular and humoral responses suggests that the macrophage migration assay is a sensitive indicator of the immunogenicity of the smaller mol. wt. HBsAg-derived polypeptides in guinea pigs.

Animals↗
PubMed1978

Non-A, non-B hepatitis transmission in chimpanzees: a project of the transfusion-transmitted viruses study group.

Experimental transmission of non-A, non-B hepatitis was apparently accomplished in 5 chimpanzees following inoculation with presumably infectious human sera. Administration of sera from implicated donors with normal alanine aminotransferase (ALT) values, as well as from those with abnormal ALT levels, resulted in the development of ALT abnormalities in the inoculated chimpanzees. Transmission from donors with normal ALT values implies that healthy carriers of non-A, non-B virus exist. Evidence is presented which indicates that a period of viremia precedes the clinical illness by at least 12 days.

Alanine Transaminase↗
PubMed1977

Viral hepatitis.

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Hepatitis B Antigens↗
PubMed1977

Experimental carcinoma of liver in macaque monkeys exposed to diethylnitrosamine and hepatitis B virus.

The effects of treatments with diethylnitrosamine (DENA) and hepatitis B virus (HBV) on macaque monkeys were investigated by virus serology and by light and electron microscopy. The experimental groups comprised 43 newborn or juvenile cynomolgus and rhesus monkeys of both sexes. HBV neither had a carcinogenic effect nor increased the oncogenic effect of DENA. However, HBV given to juvenile primates before treatment with DENA resulted in subsequent gross and microscopic alterations consistent with mild hepatitis and postnecrotic cirrhosis; multifocal liver carcinoma apparently developed within these cirrhotic nodules. The pathologic findings in the experimental animals were strikingly similar to those observed in liver cancer patients.

Animals↗