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Biomedical subjects

A Haigh

Publications and source records attributed to A Haigh.

13 recordsLinked to original sources
PubMed1999

Sex differences in beliefs about aggression: opponent's sex and the form of aggression.

Previous studies show that men endorse instrumental beliefs about aggression to a greater extent than women, whereas women endorse expressive beliefs to a greater extent than men. However, men and women indicate that they have different opponents in mind when thinking about aggression, and existing measures may emphasize physical forms of aggression. Therefore, beliefs about aggression were examined when the type of aggression (physical or verbal) and the sex of the opponent (same sex or opposite-sex partner) were specified, among a sample of 200 students. Expressive beliefs were higher and instrumental beliefs lower for an opposite-sex partner and for physical aggression. The characteristic sex difference applied across all manipulations for expressive beliefs, but not for instrumental ones: men showed higher scores than women only for same-sex physical aggression. Higher instrumental (but not lower expressive) scores were also found among those who based their responses on real rather than hypothetical events. The sex difference in instrumental beliefs for same-sex physical aggression was largely confined to respondents using a hypothetical event. As in previous studies, instrumental and expressive beliefs were relatively independent of one another. The position that the beliefs represent rhetorical devices is assessed in the light of these findings.

Adolescent↗
PubMed1995

Fused pyrazine mono-N-oxides as bioreductive drugs. III. Characterization of RB 90740 in vitro and in vivo.

RB 90740 is the lead compound in a series of aromatic mono-N-oxide bioreductive drugs. The compound shows considerably greater toxicity towards hypoxic verses aerobic mammalian cells in vitro. The differential in concentration required to give the same level of cell killing under these conditions ranges from 3.5 in a human bronchio-alveolar tumor cell line up to 120 in a rodent cell line defective in the repair of DNA strand breaks. The ability of RB 90740 to cause DNA strand breaks under hypoxic conditions was confirmed by alkaline sucrose gradient and pulsed field gel electrophoresis techniques. Despite these properties demonstrated in vitro, RB 90740 was shown not to be cytotoxic to hypoxic cells in experimental murine tumors in vivo. This may be due, in part, to the level of hypoxia (< 0.02% O2) necessary to produce toxicity in vitro.

Animals↗
PubMed1994

Factors affecting sensitivity to EO9 in rodent and human tumour cells in vitro: DT-diaphorase activity and hypoxia.

Twenty-three human tumour cell lines (lung, breast, and colon) and eight rodent cell lines were evaluated for their sensitivity to the quinone-based anticancer drug EO9 [3-hydroxymethyl-5-aziridinyl-1-methyl-2-(1H indole-4,7-dione)prop-beta-en-alpha-o1]. Sensitivity was compared with the intracellular levels of DT-diaphorase, and cell lines showing highest enzyme activity tended to be the most sensitive to EO9. The role of DT-diaphorase in determining drug sensitivity was confirmed by using the enzyme inhibitor dicoumarol, which protects cells containing high levels of DT-diaphorase from the cytotoxic action of EO9. Hypoxia increased the cytotoxicity of cells containing low but not high levels of DT-diaphorase, implying that both 1- and 2-electron reductive activation processes can be important for expression of EO9 toxicity. It is concluded that EO9 is a potentially useful agent in the enzyme directed approach to the use of bioreductive drugs in cancer therapy.

Animals↗
PubMed1992

DNA ligands as radioprotectors: molecular studies with Hoechst 33342 and Hoechst 33258.

Following earlier reports of radioprotection of cells by Hoechst 33342, we have investigated radioprotection of isolated DNA by the minor groove binders Hoechst 33258 and Hoechst 33342. Analysis of radiation-induced single strand breakage in plasmid DNA (pBR322) showed concentration-dependant protection, up to a dose-modifying factor of 9.3 for 25 microM Hoechst 33258, at which the ligand: bp ratio was 0.67. Since the ligands bind at discrete sites along DNA, sequencing gel analysis was used to investigate the radioprotective effects of the ligands both at and between the ligand-binding sites. These experiments showed that although protection was more pronounced at the binding sites, there was also some reduction in strand-breakage between binding sites. Detailed analysis at a particular site, the EcoR1 site in a 3'-32P-endlabelled 100bp restriction fragment from pBR322, showed that protection was most pronounced at the 'inner T': GAATTC. Irradiation of a synthetic oligodeoxynucleotide containing a single ligand-binding site, and labelled at the 5'-end, gave the expected doublet bands in high resolution gels, corresponding to fragments with 3'-phosphoryl- and 3'-phosphorylglycollate terminii. In the Hoechst 33258-protected sample, the 3'-phosphorylglycollate band was preferentially suppressed within the binding site. These results, together with published crystal structure data for a Hoechst 33258/dodecamer complex, suggest that the site-specific radioprotection may be due to H-atom donation from the benzimidazole NH groups in the ligand to radiation-induced radicals on 4'-deoxyribosyl carbons. In contrast to the experiments with purified DNA, in which the two ligands yielded similar results, Hoechst 33342 was a much more active radioprotector in experiments with intact cells. For 20 microM Hoechst 33342, the dose-modifying factor was 1.7 at 1% survival and 1.3 at 10% survival, whereas the same level of Hoechst 33258 yielded barely detectable protection, perhaps due to a demonstrably lower cellular uptake. Presumably the radioprotection of cells by Hoechst 33342 is due to suppression of DNA strand breakage, and further investigation of the protection mechanism(s) should enable development of improved radioprotectors.

Base Sequence↗
PubMed1990

Characterization of a cellular factor which interacts functionally with Oct-1 in the assembly of a multicomponent transcription complex.

Induction of transcription of the immediate-early (IE) genes of herpes simplex virus involves the assembly of a DNA-binding complex containing the viral protein Vmw65 and the cellular transcription factor Oct-1. We show that Oct-1 is not sufficient for complex formation and that another cellular factor(s) which is absolutely required for complex formation can be separated from Oct-1 under native conditions. We have purified this factor by approximately 100-fold using DNA-cellulose, ion-exchange and size-exclusion chromatographies. The assay used throughout the purification procedure follows the ability of the cellular factor to form a complex when added to purified Oct-1, Vmw65 and an IE specific DNA probe. The complex forming factor (CFF) had a sedimentation coefficient of about 4.4 S (i.e. molecular mass of about 70K, under non-denaturing conditions) and the polypeptide profile of highly purified CFF demonstrated two major species with molecular masses of 80K and 70K. Unequivocal association of either of these two species with CFF activity could not presently be demonstrated due to the sensitivity of CFF to denaturation. CFF, when tested on its own or in the presence of Vmw65, did not bind to the IE-specific consensus motif. We have also used deletion mutants of Oct-1 to show that the POU domain of this protein was sufficient for CFF-dependent complex formation with Vmw65. Deletions of the POU specific region of Oct-1 significantly reduced the complex forming ability, although detectable levels of complex were reconstituted using Vmw65, CFF and just the homeodomain of Oct-1.

Animals↗
PubMed1990

Interference with the assembly of a virus-host transcription complex by peptide competition.

Induction of transcription of the immediate-early (IE) genes of herpes simplex virus (HSV) involves the assembly of a DNA-binding complex containing the cellular transcription factor Oct-1 and the virus regulatory protein Vmw65 (VP16). Complex assembly can be observed using deletion variants of Vmw65 which lack the acidic C-terminal activation domain and are therefore defective for IE transactivation. Similar variants of Vmw65 interfere with IE activation by the normal protein, and with HSV replication. It has therefore been suggested that dominant interfering products of viruses such as HSV and HIV could be used in a form of intracellular immunization against virus infection. Here we report that a small peptide overlapping a region of Vmw65 which is critical for complex assembly specifically inhibits assembly of the complex but has no observed effect on the DNA-binding activity of the cellular factor alone. Selective interference with the assembly of transcription complexes by short peptides corresponding to functionally critical regions of virus regulatory proteins may be more feasible than the use of defective polypeptides as an antiviral strategy based on competitive interference.

Amino Acid Sequence↗
PubMed1990

Radiation sensitization by an iodine-labelled DNA ligand.

An iodinated DNA ligand, iodo Hoechst 33258, which binds in the minor groove of DNA, enhances DNA strand breakage and cell killing by UV-A irradiation. The sites of UV-induced strand breaks reflect the known sequence specificity of the ligand.

Animals↗
PubMed1989

Hypertension in the elderly.

Recent studies have indicated the need to modify criteria for the diagnosis of hypertension in the elderly. This audit uses computerised records to identify the population at risk and suggests that elderly hypertensives may now be overdiagnosed and overtreated.

Aged↗
PubMed1988

Direct combinatorial interaction between a herpes simplex virus regulatory protein and a cellular octamer-binding factor mediates specific induction of virus immediate-early gene expression.

We provide evidence for a novel mechanism of transcriptional regulation in which the immediate-early (IE) transactivating protein of herpes simplex virus, Vmw65, is assembled into a specific DNA-binding complex together with a cellular octamer-binding factor (TRF). The assembly of Vmw65/TRF complex requires not only the core TRF recognition site, but also flanking sequences which are dispensable for TRF binding alone. We show from functional analyses that TRF binding by a motif is required but not sufficient to confer induction on a heterologous promoter, and it is the ability of the motif to allow TRF/Vmw65 complex assembly which correlates with functional activity. Thus, for the induction of HSV IE expression, Vmw65 forms a complex with TRF by recognition of the specific subset of appropriately flanked TRF binding sites present in each of the IE genes. This mechanism may provide a paradigm for the selective utilization of the same transcription factor in differential gene expression.

Base Sequence↗
PubMedDate not supplied

Clinical protocols herald new era of nursing documentation.

Documenting care tends to be a time-consuming process and information is often replicated. This paper describes how documentation was changed in one acute hospital trust to reflect UKCC guidelines and for use by all disciplines. Evaluation suggests that less time is spent writing records and that those records are more complete.

Aged↗