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Biomedical subjects

J Hauser

Publications and source records attributed to J Hauser.

At least 37 records · Page 2Linked to original sources

Kinetics of inhibition of papovavirus DNA synthesis by superinfection with adenovirus 2 and non-defective adenovirus 2-simian virus 40 hybrid viruses.

Simian Virus 40 (SV40) DNA synthesis is inhibited in monkey cells by superinfection with adenovirus 2 (Ad2) and various non-defective Ad2-SV40 hybrid viruses. Similarly, BKV (a human papovavirus) DNA synthesis is inhibited in human cells by superinfection with Ad2. Kinetic studies indicate that inhibition begins during the early phase of the Ad2 lytic cycle. Superinfection with Ad2 does not significantly alter the formation of SV40 T antigen. Superinfection with Ad2 late in SV40 lytic cycle is less efficient in the inhibition of SV40 DNA synthesis, and the onset of Ad2 DNA synthesis is delayed, compared to superinfection early in the SV40 lytic cycle. These findings suggest that the Ad2 and SV40 genomes may compete to bind an early AD2 protein which is essential for Ad2 replication, but which blocks SV40 replication.

Adenoviruses, Human

Regulation of viral transcription in cells infected with iododeoxyuridine-substituted simian virus 40 as a model for the activation by iododeoxyuridine of latent viral genomes.

5-Iododeoxyuridine (IdUrd) induces the expression of viruses in a variety of cell lines that harbor latent viral genomes. Moreover, IdUrd stimulates cellular as well as viral RNA synthesis in certain cells. In order to understand better the action of IdUrd on RNA metabolism, we have examined viral RNA synthesis in monkeys cell infected with IdUrd-substituted simian virus 40 (SV40). Extensively substituted SV40, in which 18 to 35% of the thymidine residues were substituted by IdUrd, was 100-fold less viable (by plaque analysis) than was unsubstituted SV40, although the substituted virus induced 30 to 50% as much viral-specific RNA as did the unsubstituted virus. In contrast, SV40, containing only 10 to 15% IdUrd, substitution was almost as viable as unsubstituted virus, and the substituted SV40 induced 5-fold more viral-specific RNA, as well as longer viral messenger RNA transcripts, than did the unsubstituted virus. These results suggest that the lightly substituted, mutagenized SV40 genome may produce defective proteins which fall to regulate their own transcription. Cellular DNA into which halogenated pyrimidines have been incorporated may also induce the synthesis of defective regulatory proteins, including cellular repressors of transcription which normally maintain the latent state of integrated viral genomes.

Animals

Method for determining the extent and copy number of overlapping and nonoverlapping segments of integrated viral genomes.

We analyzed the method of exhaustive hybridization of single-stranded DNA and derived a general relationship between the fraction of the probe DNA hybridized and the sizes and copy numbers of the segments of the viral genome integrated in cellular DNA. The equations employed can be used to analyze integrated DNA comprised of overlapping and nonoverlapping segments of the viral genome. Using these equations, we analyzd the adenovirus type 2 DNA content of a series of hamster cell lines transformed by adenovirus type 2 and several adenovirus type 2-simian virus 40 hybrid viruses. We found no eividence that the integrated viral DNA is comprised of overlapsping segments. However, the number of copies of the integrated segments varies between lines cloned from the same transformed isolate, and copy numbers change during in vivo passage of transformed cells.

Adenoviruses, Human

Content and expression of integrated viral DNA in hamster cells transformed by nondefective adenovirus type 2- simian virus 40 hybrid viruses.

Hamster cells transformed by adenovirus 2 (Ad2) and five nondefective Ad2-simian virus 40 (SV40) hybrid viruses are all of the Ad2-transformed phenotype. All lines accumulate Ad2 RNA and Ad2 T antigen; two hybrid-transformed lines accumulate SV40 RNA, but only one contains detectable amounts of SV40 antigens. We examines selected lines from this group of transformed hamster cells for Ad2 DNA content and viral RNA expression by using hydroxyapatite chromatography and separated strands of labeled viral DNA as probes. All lines studies contain 1 to 2 Ad2 genome equivalents per haploid equivalent of cell DNA. The expression of Ad2 RNA exhibits two distinct patterns. In one pattern, transcription of the heavy strand of Ad2 DNA is less than that of the light strand, whereas in the second pattern of Ad2 RNA expression the extent of heavy-strand transcription is greatly increased. In the two lines containing SV40 RNA, the entire SV40 (-) strand is transcribed; the (+) strand is not expressed in these cells. These patterns of viral RNA expression suggest the possibility that host promoters may play a role in regulating transcription of integrated viral DNA.

Adenoviridae

Studies on direct and indirect effects of DNA damage on mutagenesis in monkey cells using an SV40-based shuttle vector.

We are using an SV40-based shuttle vector, pZ189, to study mechanisms of mutagenesis in mammalian cells. The vector can be treated with mutagens in vitro and replicated in animal cells; resulting mutants can be selected and amplified in bacteria for DNA sequencing. This versatile vector system has allowed us to explore several different questions relating to the mutagenic process. We have studied the direct effects of template damage caused by UV or benzo[a]pyrene diolepoxide by treating vector DNA with these agents and then replicating the damaged DNA in monkey cells. Mutational mechanisms were deduced from the spectrum of mutations induced in the supF target gene of the vector DNA. To study the role of indirect effects of DNA damage on mutagenesis in mammalian cells, we have treated the cells and the vector DNA separately with DNA-damaging agents. We find that pretreatment of cells with DNA-damaging agents, or with conditioned medium from damaged cells, causes an enhancement of mutagenesis of a UV-damaged vector. Thus, DNA damage can act indirectly to enhance the mutagenic process. We also have preliminary evidence that pZ189 can be used in an in vitro DNA replication system to study the process of mutation fixation on the biochemical level. We believe that the pZ189 vector will prove to be as useful for in vitro studies of mutational mechanisms as it has been for in vivo studies.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide

[Usefulness of Widlöcher scale in assessment of psychomotor activity disorders in endogenous depression].

A group of 50 patients with a diagnosis of affective disease was examined. Dependence between the intensification of depression psychomotor activity measured according to Widlöcher scale was established. Neurophysiological factors (such as thinking productivity, letter drafting, tapping test, simple reaction time) correlated with the intensification of psychomotor activation disorders.

Adult

[Depressive disorders with psychomotor activity in patients with alcohol dependence syndrome].

In a group of 85 men with alcohol dependence syndrome occurrence of depressive symptoms was examined and the intensification of psychomotor activation disorders was assessed. 60% of patients showed symptoms of depression during alcohol intoxication. Relationship between the intensification of depressive symptoms and psychomotor activity disorders was testified.

Adult