Biomedical subjects

J Hauser

Publications and source records attributed to J Hauser.

At least 37 records · Page 2Linked to original sources

PubMed1996

A federal perspective on special education technology.

This article examines more than a decade of changes in special education research and in the use of technology. It discusses evolving research and projects funded by the Office of Special Education Programs (OSEP) and raises questions about the use of specific methodologies and about whether children with disabilities are being prepared for the world in which they will live. And, finally, it describes OSEP's Technology, Educational Media, and Materials strategic program agenda that will drive future planning and priorities.

Audiovisual Aids↗

PubMed1993

Targeting of the UmuD, UmuD', and MucA' mutagenesis proteins to DNA by RecA protein.

In addition to its critical role in genetic recombination, the Escherichia coli RecA protein plays a pivotal role in SOS-induced mutagenesis. This role can be separated genetically into three steps: (i) depression of the SOS regulon by mediating the posttranslational cleavage of the LexA repressor, (ii) activation of UmuD'-like proteins by mediating cleavage of the UmuD-like proteins, and (iii) a direct step, possibly to interact with and to target the Umu-like mutagenesis proteins to lesions in DNA. We have analyzed RecA's third role biochemically using protein affinity chromatography and an agarose-based DNA mobility-shift assay. RecA730 protein from a crude cell extract was specifically retained on UmuD and UmuD' protein affinity columns, suggesting that these proteins physically interact. Normally, neither UmuD nor UmuD' shows any affinity for DNA. In the presence of RecA protein, however, UmuD and UmuD' were targeted to DNA. RecA1730 protein, which is defective for UmuD' but proficient for MucA'-promoted mutagenesis, showed a dramatically reduced capacity to target UmuD' to DNA but was able to target a significant portion of MucA' to DNA. These data support the suggestion that the direct role of RecA protein in SOS-induced mutagenesis is to interact with and target the Umu-like mutagenesis proteins to DNA.

Bacterial Proteins↗

PubMed1993

Replication and mutagenesis of UV-damaged DNA templates in human and monkey cell extracts.

We have used in vitro DNA replication systems from human HeLa cells and monkey CV-1 cells to replicate a UV-damaged simian virus 40-based shuttle vector plasmid, pZ189. We found that replication of the plasmid was inhibited in a UV fluence-dependent manner, but even at UV fluences which caused damage to essentially all of the plasmid molecules some molecules became completely replicated. This replication was accompanied by an increase (up to 15-fold) in the frequency of mutations detected in the supF gene of the plasmid. These mutations were predominantly G:C-->A:T transitions similar to those observed in vivo. Treatment of the UV-irradiated plasmid DNA with Escherichia coli photolyase to reverse pyrimidine cyclobutane dimers (the predominant UV-induced photoproduct) before replication prevented the UV-induced inhibition of replication and reduced the frequency of mutations in supF to background levels. Therefore, the presence of pyrimidine cyclobutane dimers in the plasmid template appears to be responsible for both inhibition of replication and mutation induction. Further analysis of the replication of the UV-damaged plasmid revealed that closed circular replication products were sensitive to T4 endonuclease V (a pyrimidine cyclobutane dimer-specific endonuclease) and that this sensitivity was abolished by treatment of the replicated DNA with E. coli photolyase after replication but before T4 endonuclease treatment. These results demonstrate that these closed circular replication products contain pyrimidine cyclobutane dimers. Density labeling experiments revealed that the majority of plasmid DNA synthesized in vitro in the presence of bromodeoxyuridine triphosphate was hybrid density whether or not the plasmid was treated with UV radiation before replication; therefore, replication of UV-damaged templates appears to occur by the normal semiconservative mechanism. All of these data suggest that replication of UV-damaged templates occurs in vitro as it does in vivo and that this replication results in mutation fixation.

Animals↗

PubMed1992

The enhanced mutagenic potential of the MucAB proteins correlates with the highly efficient processing of the MucA protein.

Inducible mutagenesis in Escherichia coli requires the direct action of the chromosomally encoded UmuDC proteins or functional homologs found on certain naturally occurring plasmids. Although structurally similar, the five umu-like operons that have been characterized at the molecular level vary in their ability to enhance cellular and phage mutagenesis; of these operons, the mucAB genes from the N-group plasmid pKM101 are the most efficient at promoting mutagenesis. During the mutagenic process, UmuD is posttranslationally processed to an active form, UmuD'. To explain the more potent mutagenic efficiency of mucAB compared with that of umuDC it has been suggested that unlike UmuD, intact MucA is functional for mutagenesis. To examine this possibility, we have overproduced and purified the MucA protein. Although functionally similar to UmuD, MucA was cleaved much more rapidly both in vitro and in vivo than UmuD. In vivo, restoration of mutagenesis functions to normally nonmutable recA430, recA433, recA435, or recA730 delta(umuDC)595::cat strains by either MucA+ or mutant MucA protein correlated with the appearance of the cleavage product, MucA'. These results suggest that most of the differences in mutagenic phenotype exhibited by MucAB and UmuDC correlate with the efficiency of posttranslational processing of MucA and UmuD rather than an inherent activity of the unprocessed proteins.

Bacterial Proteins↗

PubMed1992

Simian virus 40 (SV40) small t antigen inhibits SV40 DNA replication in vitro.

We describe a biochemical function of simian virus 40 small t antigen, the inhibition of simian virus 40 large T antigen-mediated viral DNA replication in an in vitro replication system. Our results suggest that in this system, small t antigen prevents protein phosphatase 2A-mediated activation of large T antigen.

Antigens, Polyomavirus Transforming↗

PubMed1991

Extremely long protection by pyrazole derivatives against chemically induced gastric mucosal injury.

We tested the hypothesis that the gastrotoxicity of ethanol and other damaging agents is influenced through the modulation of alcohol dehydrogenase (ADH) by using either the ADH-inhibitor pyrazole or the noninhibitor derivatives of pyrazole. In time course experiments, the protection by both compounds was evident up to 48 hr before ethanol administration. Both drugs were also protected, from about 24 hr, from gastric mucosal damage induced by aspirin and hydrochloric acid. In order to examine the role of endogenous prostaglandins and sulfhydryls in this protection, indomethacin and N-ethylmaleimide were used, of which only the sulfhydryl alkylator antagonized (by about 50%) the protection by pyrazole and 3-methylpyrazole. Studies with monastral blue B revealed the protective role of both pyrazole and 3-methylpyrazole against early vascular injury in the gastric mucosa. We conclude that because both the ADH-inhibitor pyrazole and the noninhibitor derivatives of pyrazole exert gastro-protection, and because both compounds protect against aspirin and HCI, ADH inhibition is not involved in this protection. We also suggest that although prostaglandins appear to have minimal involvement in the mechanism of protection, endogenous sulfhydryls may be important mediators. Furthermore, the functional and structural mechanism of this protection seems to be the prevention of acute vascular injury.

Amides↗

PubMed1990