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Biomedical subjects

M J Austin

Publications and source records attributed to M J Austin.

At least 19 recordsLinked to original sources
PubMed2000

Arabidopsis map kinase 4 negatively regulates systemic acquired resistance.

Transposon inactivation of Arabidopsis MAP kinase 4 produced the mpk4 mutant exhibiting constitutive systemic acquired resistance (SAR) including elevated salicylic acid (SA) levels, increased resistance to virulent pathogens, and constitutive pathogenesis-related gene expression shown by Northern and microarray hybridizations. MPK4 kinase activity is required to repress SAR, as an inactive MPK4 form failed to complement mpk4. Analysis of mpk4 expressing the SA hydroxylase NahG and of mpk4/npr1 double mutants indicated that SAR expression in mpk4 is dependent upon elevated SA levels but is independent of NPR1. PDF1.2 and THI2.1 gene induction by jasmonate was blocked in mpk4 expressing NahG, suggesting that MPK4 is required for jasmonic acid-responsive gene expression.

Alleles↗
PubMed1999

Functional genomics: technological challenges and opportunities.

In April, the Merck Genome Research Institute and the National Cancer Institute's Cancer Genome Anatomy Project, both supporters of functional genomics technology development and research, brought together a group of 27 scientists working at the forefront of this new field. Here we report on the presentations, discussions, and outcomes from this highly interactive and stimulating meeting held at the Banbury Center.

Animals↗
PubMed1997

Service integration: something old and something new.

The authors trace the definition and challenges of "service integration," variously known over time as "collaboration," "coordination," "human services integration," and "one-stop shopping." While the common use of service integration terminology currently may seem to indicate a consensus in favor of a broad systemic reform, motivations and expectations for service integration differ significantly among different players in the service system. The authors conclude that service integration cannot be defined by a particular service model or outcome, but instead should be conceived of as an ongoing reform process. This process, when well-designed and implemented with long-term vision, can reduce duplication, strengthen communities, and improve client outcomes.

California↗
PubMed1996

Understanding socially inhibited behaviors in managers.

The authors' purpose in this study is to define and highlight socially inhibited behaviors among managers, explore the implications of these behaviors for the workplace, identify ways to assist inordinately shy managers, and help staff to understand and relate more effectively when subjected to an inhibited manager. The authors search for the origins of shyness, surveying the various perspectives in personality theory and within the concept of situational causality.

Administrative Personnel↗
PubMed1995

Selective damage to the active X chromosome by camptothecin and amsacrine as determined by an allele-specific alkaline unwinding assay.

Previous studies with MCF-7 cells demonstrated that several agents induce greater strand breakage in active genes than in nontranscribed centromeric regions. To better assess the effects of gene activity and inactivity, an allele-specific DNA strand break assay was developed, which allowed direct comparison of damage at a specific genetic locus on the active and inactive X chromosomes. The ZP lymphoblastoid cell line is heterozygous at the glucose-6-phosphate dehydrogenase (G6PD) locus, and the unexpressed (A) allele on the inactive X chromosome contains a FokI restriction site that is lacking in the expressed (B) allele on the active X. ZP cells were treated with camptothecin or amsacrine, and subjected to alkaline-induced DNA unwinding. Following detergent lysis and digestion of single-stranded DNA with S1 nuclease, the remaining double-stranded DNA was isolated and subjected to polymerase chain reaction (PCR) with primers that flank the polymorphic FokI site, with [alpha-32P]dCTP being added in the last PCR cycle. The resulting labeled PCR product was cleaved with FokI to assess the A/B allele ratio in the double-stranded DNA fraction. Treatment with camptothecin and amsacrine increased the apparent A/B ratio by factors of 2-3 and 1.5-2 respectively, indicating that the active B allele is preferentially damaged by these agents.

Alleles↗
PubMed1994

Single base-pair deletions induced by bleomycin at potential double-strand cleavage sites in the aprt gene of stationary phase Chinese hamster ovary D422 cells.

One possible mechanism for the generation of deletion mutations is inaccurate repair of DNA double-strand breaks. In an attempt to detect such aberrant repair events in intact cells, confluent stationary phase cultures of chinese hamster ovary D422 cells, which are hemizygous for aprt, were treated for two days with low concentrations of bleomycin, and aprt mutant clones were selected and analyzed by polymerase chain reaction and DNA sequencing. Bleomycin was quite mutagenic in stationary phase cells, increasing the mutant frequency by five to 40-fold at 5 to 50% survival. While spontaneous mutations generated under these conditions were predominantly base substitutions, the majority of the bleomycin-induced mutations were very small deletions, with lesser numbers of large deletions/rearrangements and base substitutions. Although the small deletions tended to be clustered in several short segments of the gene, nucleosome positioning studies indicated that there was no consistent phasing of nucleosomes in aprt, suggesting that the clustering was due to sequence specificity rather than chromatin structure. About half of the bleomycin-induced mutations were single-base-pair (-1) deletions, and the majority of these involved deletion of one C in a G-Cn sequence (n > or = 2). At such sites, bleomycin is known to induce double-strand breaks by fragmentation of deoxyribose moieties at the same sequence position in both strands, resulting in a blunt-ended double-strand break with 5'-phosphate and 3'-phosphoglycolate termini. Thus, this sequence specificity is consistent with a model in which bleomycin-induced -1 deletions are generated by a double-strand break rejoining process involving removal of phosphoglycolate moieties from both 3' ends, followed by blunt-end ligation. The results support the view that repair of free radical-mediated double-strand breaks in mammalian cells in G1/G0 phase can be effected by such simple end-joining mechanisms, without the need for homologous recombination.

Adenine Phosphoribosyltransferase↗
PubMed1993

Common fragile site expression in lymphocytes from an individual mosaic for trisomy 8.

During the course of a survey of fragile site expression in lymphocytes from twins one member of a dizygotic pair was found to be mosaic for trisomy 8. One hundred fifty metaphases from this individual were analyzed (100 treated with aphidicolin and 50 untreated); 43% were 46,XY and 57% 46,XY,+8. No differences were observed between the treated and control cultures in either the proportions of normal and trisomic metaphases or the overall or specific fragile site expression in the normal and trisomic cells.

Adolescent↗
PubMed1993

Small deletion and insertion mutations induced by the topoisomerase II inhibitor teniposide in CHO cells and comparison with sites of drug-stimulated DNA cleavage in vitro.

Sixty-five teniposide-induced mutations at the hemizygous aprt locus of CHO D422 cells were analyzed by polymerase chain reaction and DNA sequencing. Most (63%) of the mutations were deletions, duplications and insertions of various sizes, with the majority being less than 20 base-pairs. The remaining mutations were base substitutions, the majority of which were transversions. A significant correspondence was found between the teniposide-induced small deletion/duplication mutations and sites of teniposide-stimulated DNA strand cleavage by topoisomerase II in vitro. In particular, sequences which were deleted in one or more of the mutants showed a much higher incidence of strong cleavage sites than sequences not involved in deletions. However, the exact positioning of the cleavage sites with respect to the deletion termini was variable. The data did not suggest any unified model to account for all the mutations, but most of the deletions and duplications could be accounted for by one of three mechanisms: (1) double-strand break repair nonhomologous end-joining; (2) replication slippage/misalignment; and (3) addition or deletion of a few nucleotides at free 3' ends left by topoisomerase II, as previously suggested for similar mutations in phage T4. There was no evidence that topoisomerase II subunit exchange was a significant mechanism of mutagenesis in this system.

Animals↗
PubMed1992

DNA sequence analysis of mutations induced by melphalan in the CHO aprt locus.

In previous work, we established that treatment with melphalan (L-phenylalanine mustard) produced a predominance of A.T-->T.A transversions in the Simian virus 40 (SV40)-based shuttle vector pZ189 during replication in human 293 cells. Mutations were induced with varying doses (4-12 microM) melphalan in the aprt gene of the hemizygous Chinese hamster ovary (CHO) cell line D422 to determine whether a similar mutation spectrum would be observed in an endogenous gene. DNA sequence alterations were determined for 39 spontaneous and 41 melphalan-induced independent mutant clones. Other than a predominance of transversions in both systems, the spectrum of melphalan-induced aprt mutations bears little resemblance to the spectrum observed in the supF gene of the shuttle plasmid pZ189. In aprt, mutations at G.C base pairs (bp) predominated (29 of 41 base substitutions). Significantly enhanced mutagenesis was observed at 5' G-G-C 3' and 5' G-G-C-C 3' sites in the aprt gene. Almost half of the melphalan-induced base substitutions occurred at 5' G-N-C 3' sequences, which are believed to be potential interstrand crosslink sites.

Adenine Phosphoribosyltransferase↗
PubMed1992

Aphidicolin-inducible common fragile-site expression: results from a population survey of twins.

Common chromosomal fragile sites appear to be ubiquitous in humans and other mammals, and, although the molecular basis and function of these sites remain an enigma, it has been speculated that they may be a cytogenetic expression of gene activity. A population survey of 28 twin pairs was conducted to assess the heritability of common fragile-site expression. Our data yielded a heritability estimate of .88 for total site expression, suggesting that these sites may result from some common process that is under relatively stringent genetic control. An analysis of the expression of individual autosomal sites revealed that expression on both homologues in the same cell occurred more frequently than expected.

Adolescent↗
PubMed1991

Expression of common fragile sites on the X chromosome corresponds with active gene regions.

The expression of common chromosomal fragile sites on human chromosomes has been proposed to be a cytogenetic expression of gene activity. Distinctive patterns of expression of two common fragile sites on the human X chromosome were observed in females. The fragile site at Xp22.31, located in a band region that contains genes which escape X inactivation, was expressed on both X chromosomes. By contrast, the fragile site at Xq22.1, in a region assumed to be subject to X inactivation, was expressed almost exclusively on one X, the active X chromosome. These findings provide evidence that common fragile site expression only occurs in regions with active genes.

Aphidicolin↗
PubMed1991

The postanesthesia trauma patient: a case study.

With the number of trauma centers across the country on the increase, it is vital that the PACU nurse understands anesthesia for the trauma patient. The purpose of this article is to describe anesthetic agents, airway management, fluid replacement, and complications common in the trauma patient. Nursing interventions also are identified for the unstable or potentially unstable trauma patient.

Humans↗