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Biomedical subjects

J Summers

Publications and source records attributed to J Summers.

At least 109 records · Page 6Linked to original sources
PubMed1986

Experimental infection of the woodchuck (Marmota monax monax) with woodchuck hepatitis virus.

Six woodchucks, 10 1/2 months of age, injected intramuscularly with 0.02 ml of woodchuck hepatitis virus (WHV)-positive serum and two woodchucks of similar age and origin injected with phosphate buffered saline were studied by serial blood samples and liver biopsy sections over an 18 week period. Serum samples were assayed for WHV surface antigen (WHsAg), its corresponding antibody (anti-WHs) and antibody to WHV core antigen (anti-WHc). WHV core antigen (WHcAg) was detected in liver biopsy sections by fluorescent labeled anti-WHc, and WHsAg was detected by the Victoria blue stain. All six experimentally infected woodchucks eventually developed anti-WHs and four developed serologic and histologic signs of acute hepatitis. Hepatic lesions resembled lesions described in the livers of chimpanzees and humans with acute hepatitis B viral infections. The first histologic signs of liver change coincided with the appearance of WHsAg within the serum and WHcAg within the cytoplasm of hepatocytes. After WHcAg was no longer detected in the serum, WHsAg appeared in the cytoplasm of hepatocytes. Microfocal areas of hepatic necrosis were associated with aggregates of lymphocytes, macrophages, and a few neutrophils and plasma cells. The periportal exudate became increasingly abundant during the 18-week study period in the four animals with acute hepatitis. The results from this study indicate that acute hepatitis may be induced in the woodchuck by experimental infection with WHV. Furthermore, the woodchuck might serve as an excellent model for the study of the pathogenesis of acute viral hepatitis in man.

Acute Disease↗
PubMed1985

Deletion in chromosome 11p associated with a hepatitis B integration site in hepatocellular carcinoma.

Hepatitis B virus (HBV), a virus with known carcinogenic potential, integrates into cellular DNA during long-term persistent infection in man. Hepatocellular carcinomas isolated from viral carriers often contain clonally propagated viral DNA integrations. As small chromosomal deletions are associated with several types of carcinomas, the occurrence of chromosomal deletions in association with HBV integration in hepatocellular carcinoma was studied. HBV integration was accompanied by a deletion of at least 13.5 kilobases of cellular sequences in a human hepatocellular carcinoma. The viral DNA integration and deletion of cellular sequences occurred on the short arm of chromosome 11 at location 11p13-11p14. The cellular sequences that were deleted at the site of HBV integration were lost from the tumor cells, leaving only a single copy of the remaining cellular allele.

Animals↗
PubMed1985

Take patient rights seriously to improve patient care and to lower costs.

Administrators can increase the quality of care and lower costs by taking patient rights seriously. Small rural hospitals as well as large urban ones can do this by encouraging the patient's right to self-determination and by gaining the support of employees and community alike.

Community-Institutional Relations↗
PubMed1984

Cloning and structural analysis of integrated woodchuck hepatitis virus sequences from a chronically infected liver.

We have isolated and determined the structure of a recombinant clone in lambda phage Charon 30 which contains woodchuck hepatitis virus sequences integrated in woodchuck genomic DNA sequences. This clone, in contrast to previously reported clones (Ogston et al., Cell 29:385-394, 1982), was isolated from a chronically infected liver which never developed hepatocellular carcinoma. Southern blot analysis of viral sequences in the clone in conjunction with electron microscope heteroduplex analysis showed that the integrated viral sequences did not contain internal rearrangements, as have those from hepatomas, but were colinear with the cloned viral genome except for the deletion of approximately 500 base pairs of viral sequences (between positions 1,000 and 1,550 on the viral map). Therefore, the integration was probably a defective genome incapable of supporting viral replication. However, the complete open reading frames coding for the viral X, core, presurface , and surface antigen genes were present, indicating that the viral sequences could code for viral antigens. Southern blot analysis of the normal cellular flanking sequences, using flanking sequence probes from the clone, showed that no detectable rearrangements of cellular DNA (less than 50 base pairs) had occurred at the site of viral integration.

Animals↗
PubMed1983

Experimental transmission of duck hepatitis B virus.

Susceptibility to experimental infection with duck hepatitis B virus (DHBV) was explored, with the objective of defining procedures that were both rapid and reproducible. For the purpose of these experiments, a small flock of DHBV-free breeders was established as a source of susceptible eggs and ducklings, since ca. 10% of the ducks (all ages) from commercial flocks were DHBV infected. Intravenous inoculation of DHBV into 15-day duck embryos from the DHBV-free flock produced a persistent infection, with a high-titer viremia, in at least 80% of the injected animals. The tissue tropism of DHBV in these experimentally infected animals was similar to that associated with natural, congenital infections from viremic ducks to their progeny. Virus antigen was found not only in hepatocytes and bile duct epithelium of liver, but also in cells associated with exocrine and endocrine pancreas, and in proximal convoluted tubular epithelium of kidney. Infection of embryonic liver was rapid, as evidenced by active synthesis of DHBV-DNA by reverse-transcription of RNA by 24 hr postinjection. During this latter analysis, formation of supercoiled viral DNA appeared to precede the reverse-transcription phase of viral DNA synthesis, suggesting that this species may be important in initiation of infection.

Animals↗
PubMed1983

Characterization of the genome of the agent of erythrocyte aplasia permits its classification as a human parvovirus.

It has recently been established that infection with a virus is the most common cause of transient arrest of erythrocyte production in the bone marrow, leading to aplastic crisis, in persons suffering chronic haemolytic anaemias. The physical characteristics of this human virus have suggested that it may be a member of the Parvoviridae. We report here that extraction of nucleic acid from this virus under annealing conditions yielded a single species of double-stranded DNA 5.5 kb in length. Treatment with heat or alkali converted this DNA into a rapidly migrating form sensitive to the single-strand-specific nuclease S1. Extraction of the virion DNA under conditions of low ionic strength where annealing would not be expected to occur yielded DNA which comigrated with the 5.5 kb single-stranded molecule. The results indicate that this virus packages equal numbers of complementary DNA strands into separate virions. It is suggested that this virus can be classified as a member of the genus parvovirus.

Anemia, Hemolytic↗
PubMed1983

Protein covalently bound to minus-strand DNA intermediates of duck hepatitis B virus.

Analysis of duck hepatitis B viral DNA by gel electrophoresis, Southern blotting, and binding to benzoylated naphthoylated DEAE-cellulose showed that a protein is bound to the minus-strand virion DNA as well as to the full-length single strand, minus-strand species, and minus-strand DNA intermediates isolated from replicating complexes present in infected duck liver. By utilizing a modified dideoxynucleotidyl sequencing method, it was shown that the protein is covalently bound to the smallest detectable growing strands (ca. 30 bases) and that minus-strand synthesis begins at a unique site. These results support the notion that the protein may function as a primer for synthesis of the minus-strand DNA.

Animals↗
PubMed1982

Cloning and structural analysis of integrated woodchuck hepatitis virus sequences from hepatocellular carcinomas of woodchucks.

Woodchuck hepatitis virus (WHV), like the related hepatitis B virus, induces in its natural host hepatocellular carcinomas that contain integrated viral sequences. As a first step in determining whether and how the integrated sequences contribute to formation of the tumors in which they are found, we have cloned two such integrations of WHV and have determined their structure by restriction mapping and heteroduplex electron microscopy. The identity of the cloned sequences was confirmed by comparison of restriction sites in the clones with those located by Southern blot analysis of tumor DNA. Viral sequences in both integrations are extensively rearranged, and in neither were all parts of the viral genome represented. In this respect, the behavior of WHV in vivo is similar to that of other DNA tumor viruses that have been studied in vitro. We discuss the implications of these results in relation to possible mechanisms for tumor induction by WHV.

Animals↗
PubMed1982

Replication of the genome of a hepatitis B--like virus by reverse transcription of an RNA intermediate.

Duck hepatitis B virus, a DNA virus closely related to human hepatitis B virus, was studied in infected duck liver. Subviral particles resembling the viral nucleocapsid cores were isolated from persistently infected liver and shown to have a DNA polymerase activity that utilizes an endogenous template and synthesizes both plus- and minus-strand viral DNA. Synthesis of the viral minus-strand DNA utilized an RNA template that was degraded as it was copied. Viral plus-strand synthesis occurred on the completed minus-strand DNA. A pathway for the replication of the DNA genome of hepatitis B-like viruses by reverse transcription of an RNA intermediate is proposed.

Animals↗
PubMed1982

Asymmetric replication of duck hepatitis B virus DNA in liver cells: Free minus-strand DNA.

In order to study the replication of the DNA genome of duck hepatitis B virus, an avian virus related to human hepatitis B virus, we have characterized viral DNAs present in the livers of viremic ducks by agarose gel electrophoresis and the Southern blot procedure. In addition to relaxed circular DNA similar to virion DNA, livers contained a heterogeneous population of rapidly migrating species. The conformation of the rapidly migrating species was markedly sensitive to salt, suggesting that these species were largely single stranded. The largest major rapidly migrating species was shown to have an electrophoretic mobility that was insensitive to preheating of the DNA to 100 degrees C and was similar to that of denatured virus DNA 3 kilobases long, suggesting that this DNA was a single-stranded copy of the entire virus genome. Hybridization with strand-specific probes demonstrated that this 3-kilobase species, as well as more rapidly migrating DNAs, were predominantly minus strands.

Animals↗
PubMed1982

Novel forms of woodchuck hepatitis virus DNA isolated from chronically infected woodchuck liver nuclei.

We cloned several unique forms of woodchuck hepatitis virus, a DNA virus closely related to hepatitis B virus, from a chronically infected woodchuck liver. Each of the three clones contained more than two genome equivalents of viral sequences with extensive rearrangements and no detectable cellular sequences. From the frequency by which they were isolated from a library of recombinant clones, we estimate that they are present in approximately one copy per cell. Of a total of 11 sites at which rearrangements were mapped in the clones, 10 occurred between segments of opposite polarity, and 1 occurred between segments of the same polarity. The possible significance of these findings to the persistence of virus production in infected cells is discussed.

Animals↗
PubMed1980

Isolation, characterization, and comparison of recombinant DNAs derived from genomes of human hepatitis B virus and woodchuck hepatitis virus.

The human hepatitis B virus (HBV) and the woodchuck hepatitis virus (WHV) are closely related by several criteria and belong to the same class of DNA viruses. The DNA genomes from these viruses are difficult to obtain in quantities required for biochemical analysis. We have, therefore, cloned these two DNAs in the vector lambda gtWES and subcloned into the kanamycin resistance plasmid pA01. Comparison of the recombinant DNAs with authentic viral DNAs by specific hybridization, size, and restriction enzyme analysis suggests that the recombinants contain the complete genome of each virus. The nominal size of the cloned HBV genome was 3150 base pairs, compared to 3200 base pairs for the cloned WHV genome. The small amount of nucleic acid homology previously reported between the HBV and WHV DNAs could be demonstrated between the cloned viral DNAs.

Animals↗
PubMed1980

Virus of Pekin ducks with structural and biological relatedness to human hepatitis B virus.

A virus found in the sera of Pekin ducks appears to be a new member of the human hepatitis B-like family of viruses. This virus had a diameter of 40 nm and an appearance in the electron microscope similar to that of human hepatitis B virus. The DNA genome of the virus was circular and partially single stranded, and an endogenous DNA polymerase associated with the virus was capable of converting the genome to a double-stranded circle with a size of ca. 3,000 base pairs. An analysis for viral DNA in the organs of infected birds indicated preferential localization in the liver, implicating this organ as the site of virus replication. In all of these aspects, the virus bears a striking resemblance to human hepatitis B virus and appears to be a new member of this family, which also includes ground squirrel hepatitis virus and woodchuck hepatitis virus.

Animals↗
PubMed1979

Beyond dirty linen: linen use management as an innovative asset.

Because linen is an item used by virtually every inpatient in the hospital, hospital administrators will find that if they provide laundry managers an appropriate data base, they can motivate them to a larger role of linen use managers.

Administrative Personnel↗
PubMed1979

Serological relationship of woodchuck hepatitis virus to human hepatitis B virus.

Two antigenic systems of the woodchuck hepatitis virus have been identified. The relationship between viral antigens of the woodchuck hepatitis virus and the human hepatitis B virus was determined by using immunoprecipitation, hemagglutination, and immune electron microscopy techniques. Antigens found on the cores of the two viruses were cross-reactive. Lack of cross-reactivity between the surface antigens of the two viruses in immunodiffusion experiments suggested that the major antigenic determinants of the viral surfaces are different; however, results of passive hemagglutination tests indicated that there are common minor determinants. Nucleic acid homology, as measured by liquid hybridization, was found to be 3 to 5% of the viral genomes. The results of this study provide further evidence that woodchuck hepatitis virus is the second member of a new class of viruses represented by human hepatitis B virus. Since virus-infected woodchucks may acquire chronic hepatitis and hepatocellular carcinoma, these antigens and their respective antibodies will be useful markers for following the course of virus infection in investigations of the oncogenic potential of this class of viruses. The nucleocapsid antigen described may be a class-specific antigen of these viruses and, thus, may be useful in discovering new members of the group.

Animals↗