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Biomedical subjects

V Murray

Publications and source records attributed to V Murray.

At least 73 records · Page 4Linked to original sources
PubMed1996

Concentration of blood lead and ethnicity in the United Kingdom.

The relation between concentration of blood lead and ethnic background in 779 children was examined with the analytical results from the trace element service at the Medical Toxicology Unit (MTU), Guy's and St Thomas's Hospital Trust for the period 1980-94. The ethnic identity was determined with the first and the second names of the investigated subjects. Of the patients of European origin (European) studied 72.8% v only 50.6% of the children with origins in the Indian subcontinent (Asian) had a concentration of blood lead < 100 micrograms/l. The percentage of subgroups with concentrations above the upper acceptable limit of 200 micrograms/l was significantly higher in Asian subjects (European 5% v Asian 26.5%), with the most pronounced difference in those with concentrations of blood lead of 500 micrograms/l (European 0.8% v Asian 10.5%). This study shows that a correlation exists between Asian ethnic background and concentration of blood lead in children. Factors such as cultural habits-for example, use of traditional remedies, cosmetics, diet- and socioeconomic status, may have contributed to this results.

Asia↗
PubMed1995

The interaction of hedamycin and DC92-B in a sequence selective manner with DNA in intact human cells.

The sequence specificity of the pluramycin antibiotics hedamycin and DC92-B, was established in intact human cells using a linear amplification system. In this system an oligonucleotide primer is extended by Taq DNA polymerase up to a damage site. The products are run on a DNA sequencing gel and the damage can be determined to the exact base pair. The human repetitive alpha RI DNA was used as the target DNA sequence for these experiments. It was found that G residues were the main site of adduct formation, for both hedamycin and DC92-B. The sequences 5'-TGT and 5'-CGT were the most intense sites of DNA damage. A comparison of the DNA damage intensity in intact cells and purified DNA revealed that the sequence position of adduct formation was very similar in the two environments. However, a densitometric comparison of the damage intensity in the two environments revealed significant differences. Two regions were found (120 and 130 bp in length) where the damage intensity was relatively lower in intact cells compared to purified DNA. But at the boundaries of these sequences, there were regions (approx. 50-60 bp long) that were relatively more damaged in intact cells compared to purified DNA. One explanation of this phenomenon is the presence of a protecting nucleosome core on each of the 120/130 bp regions and flanking nucleosome linker regions of 50-60 bp. This postulated sequence phasing of the nucleosomes corresponds almost exactly with the major nucleosome phasing found in African green monkey cells. Also the centromere protein B binding site is found in the border region between the nucleosome core and linker DNA regions. Hedamycin and DC92-B produced nearly identical results in this human cell system.

Anthraquinones↗
PubMed1995

Comparison of the sequence selectivity of the DNA-alkylating pluramycin antitumour antibiotics DC92-B and hedamycin.

The sequence selectivity of DNA alkylation by the recently isolated pluramycin antitumour antibiotic DC92-B has been investigated using two methods: a piperidine-induced strand-breaking procedure and a Taq DNA polymerase/linear amplification method. These techniques reveal that guanines are the most reactive sites for alkylation and that the level of adduct formation at these sites is clearly sequence dependent. The highest levels of alkylation occurred at isolated guanines located in 5'-CGT sequences and also at the 5'-G in some 5'-CGG sequences. Isolated guanines in 5'-TGT sequences were also quite reactive. We have also re-examined, in parallel, the sequence selectivity of binding of the structurally-related compound hedamycin: the first known example of a bis(epoxide)-containing, DNA-alkylating pluramycin. Our studies included a more extensive sequence analysis of hedamycin binding than that previously reported and we are able, therefore, to define more precisely the sequence preference. Despite significant differences in the stereochemistry and substitution of their bis(epoxide) sidechains, hedamycin and DC92-B exhibited very similar sequence selectivities in our assays.

Alkylation↗
PubMed1994

Comparison of the sequence specificity of cis-diamminedichloroplatinum (II) damage in guanine- and 7-deazaguanine-containing DNA.

The N7 of guanine is thought to be the primary target for adduct and crosslink formation between cisplatin and DNA. However, reactive sites in DNA other than the N7 of guanine may also participate in the formation of adducts with cisplatin. The possibility that these interactions arise and form DNA polymerase blocking lesions was investigated by primer extension reactions with Taq DNA polymerase. To differentiate between damage produced at relatively weak sites from those formed at the N7 of guanine, a modified DNA template was synthesised with the N7 of guanine replaced with a carbon atom. This was achieved in a PCR designed to incorporate 7-deazaguanine instead of normal guanine. The sequence specificity of cisplatin damage in the modified and unmodified DNA substrates was compared (after linear amplification) by DNA sequencing gel analysis. For concentrations of cisplatin (1 to 5 microM) that induce blocking lesions in normal DNA, no significant damage was observed in the modified DNA. This confirmed that the N7 of guanine is the major site of adduct formation in normal DNA. At higher concentrations of cisplatin (50 microM and 100 microM), lesions were found at AA dinucleotides and other novel sites in the modified DNA. These results indicate that the N7 of guanine is not required in the formation of some cisplatin adducts.

Base Sequence↗
PubMed1994

Ultraviolet light-induced cleavage of DNA in the presence of iodoHoechst 33258: the sequence specificity of the reaction.

IodoHoechst 33258 sensitizes DNA to cleavage by near ultraviolet light (UV-A). Following an earlier study which showed that the UV-induced cleavage is at discrete locations corresponding to the ligand binding sites, this paper reports a more extensive analysis of the sequence specificity of cleavage. The experiments involved use of double-stranded DNA synthesised on primed M13 templates. Analysis of cleavage in a 280bp sequence in M13mp18 and a 310bp sequence in three M13mp9 clones ('alpha-32', 'alpha-82' and 'alpha-22') derived from human alpha-DNA, showed that for all of the twenty-nine strong and very strong damage sites, cleavage was at the 3' end of a run of three or more consecutive AT base pairs. The extent of cleavage was higher for sites with consecutive Ts than for consecutive As, and greatest for the sequence cTTTTca. Comparison of three closely-related alpha-DNA clones enabled assessment of single bp changes and essentially confirmed the results of detailed analysis of binding cleavage sites in mp18 and alpha-32. Decreasing the input ratio of iodoHoechst/per bp DNA from 0.13 to 0.013 altered the sequence specificity, and sites possessing only three consecutive AT bps were generally not cleaved. The contributions of both the strength of ligand binding and the efficiency of photolytic cleavage to the overall extent of cleavage by UV/iodoHoechst are discussed, in view of the potential utility of the ligand as a probe of DNA conformation.

Bacteriophage M13↗
PubMed1994

Specificity in splicing.

Considerable information about the process of pre-mRNA splicing has accumulated, but the mechanism by which highly accurate splicing is achieved is unresolved. Fifteen years ago we proposed that accuracy in splicing might depend on small RNA molecules (splicer RNAs) which hybridise across adjacent exon termini, or intron termini. Gene expression, including alternative splicing, could be controlled by the transcription of specific splicer RNA genes. We re-assess our model here, in the light of subsequent developments.

Alternative Splicing↗
PubMed1994

An outbreak of illness among schoolchildren in London: toxic poisoning not mass hysteria.

STUDY OBJECTIVE: To determine the cause of an outbreak of acute gastrointestinal illness that occurred shortly after lunch in children attending a school in London, UK. DESIGN: A questionnaire survey of children at the affected school was carried out on the day after the incident. Microbiological, environmental, and toxicological investigations were also undertaken. SETTING: A school in London, UK. PARTICIPANTS: Altogether 374/468 (80%) of the children who had eaten lunch at the school on the day of the incident completed a questionnaire. MAIN RESULTS: There was a significant association between illness and the consumption of raw cucumber (relative risk = 6.1; 95% confidence interval 2.2, 16). Microbiological investigation of the foods served at lunch did not show any pathogens and toxicological investigations suggested that the cucumbers were contaminated by a pesticide. CONCLUSIONS: Although the outbreak displayed several typical features of mass psychogenic illness, the most probable cause was a toxic chemical present in cucumber served at lunch. Those responsible for investigating outbreaks of illness should be aware of the possible toxicological causes and the appropriate modes of investigation. They should be wary of too readily attributing a psychogenic cause to unusual outbreaks of acute illness in schoolchildren.

Acute Disease↗
PubMed1994

Toxicological problems resulting from exposure to traditional remedies and food supplements.

The National Poisons Unit, London, carried out a pilot survey to investigate the frequency and severity of adverse effects/toxicity from exposure to traditional medicines and food supplements reported to the Unit. Enquiries related to suspected poisoning events were reviewed retrospectively from January 1983 to March 1989, and prospectively in 1991. Further information about cases identified by the prospective review was obtained, when appropriate, by follow-up questionnaire, clinical consultation by a consultant toxicologist, toxicological analyses of samples from patients and from products, and botanical identification of dried plant material. In total, 5536 enquiries were identified. Symptoms were reported in 657 (12%) of these. There was a large number of reports of accidental ingestion of vitamin preparations by children under 5 years. Appropriate assessment was possible in only relatively few cases, due to insufficient documentation, and poor labelling of certain products. A probable link between exposure and adverse effects was identified in 42 cases, and was highly probable in two. Heavy metal poisoning resulting from use of contaminated traditional remedies was confirmed in 5 cases. There was evidence that some patients took excessive doses of food supplements, without realising that this might result in toxic effects. The results of this pilot study suggest that there is a need for further surveillance to provide an appropriate risk assessment of food supplements and herbal remedies, improved quality control and labelling of these products, and increased awareness of their potential hazard.

Adolescent↗
PubMed1994

Dideoxy genomic sequencing of a single-copy mammalian gene using more than two hundred cycles of linear amplification.

We explored the possibility of using a large number of reaction cycles to achieve genomic DNA sequencing in single-copy mammalian genes. A section of the beta-globin promoter was sequenced directly from a sample of human white blood cell DNA. The sequencing fragments were extended from a single, 5'-terminal-labeled oligonucleotide primer by Taq DNA Polymerase in the presence of dideoxyribonucleotides and more than 200 thermal cycles of denaturation, annealing and extension. The labeled sequencing fragments produced in this linear amplification were detected after electrophoresis on a DNA-sequencing gel. We propose that this scheme could be adopted in some instances as an alternative to conventional sequencing.

Base Sequence↗
PubMed1994

A polymerase chain reaction on human alphoid DNA produces a characteristic ladder of bands.

A polymerase chain reaction (PCR) was performed on the tandemly repeated human alphoid DNA sequence. A characteristic ladder of bands was produced which differed by 171 (or 340) base pairs. This laddering phenomenon occurs because the two oligonucleotides can bind within the same monomer or in neighbouring monomers. In the latter case a larger PCR product is produced which is 171 bp or a multiple of 171 base pairs greater in size. The alphoid DNA PCR is very sensitive because a repeated sequence is amplified. Hence it could have applications in archaeology or forensic science.

Base Composition↗