Search PubMed⌕ Search

Biomedical subjects

K Gardiner

Publications and source records attributed to K Gardiner.

At least 91 records · Page 5Linked to original sources
PubMed1995

cDNA selection from 10 Mb of chromosome 21 DNA: efficiency in transcriptional mapping and reflections of genome organization.

The technique of cDNA hybridization selection has been applied individually to 16 YAC clones mapping to various regions of the long arm of human chromosome 21. YACs represented approximately 10 Mb of non-overlapping DNA, and cDNA sources included fetal brain, whole fetus, and adult testes, thymus, liver and spleen. Sequencing, Northern analysis, RT-PCR and cDNA library screenings have been used to identify and partially characterize a non-redundant set of novel genes. A preliminary analysis strategy of the selected cDNAs has proven rapid and effective for isolation of the more highly represented genes and is suitable for survey transcriptional mapping efforts. By scaling up to screen > 1000 cDNA fragments per 100 kb of YAC DNA, more rare transcripts are identified and lead to comprehensive gene maps. Strong regional variations in transcriptional activity were observed, with gene densities ranging from < 1/2000 kb to > 1/15 kb. This effort has produced a large number of new genes of potential relevance to Down Syndrome.

Adult↗
PubMed1995

Urinary 1-hydroxypyrene: a biomarker for polycyclic aromatic hydrocarbon exposure in coal liquefaction workers.

This study was undertaken to assess the suitability of urinary 1-hydroxypyrene (1-OHPyr) as a biological marker of polycyclic aromatic hydrocarbon (PAH) exposure in coal liquefaction workers. This is believed to be the first evaluation of the method in coal liquefaction workers. Ten workers were selected from a group of 30 workers considered likely to be at risk of contamination from PAHs by virtue of their jobs. Spot urine samples were collected at the start of a work period and at the end of each work shift, with analysis of 1-OHPyr being undertaken by high-performance liquid chromatography linked to a fluorescence detector. Exposure was assessed by the completion of questionnaires. Excretion of 1-OHPyr increased significantly over the working period, and there was a significant increase in 1-OHPyr where start-shift and end-shift samples were taken over one shift. A significant decrease in 1-OHPyr was found during breaks away from work.

Adult↗
PubMed1995

The methodological problems of multinational epidemiological studies with particular reference to carbon black studies.

The reduction in the size of available populations within a single company or country has forced researchers to use multicentric and even multinational study designs. This paper describes an example of this approach by means of reviewing the published carbon black literature with specific regard to the epidemiological difficulties, the study design used in the multinational European carbon black study, and a discussion of the difficulties and weaknesses encountered. A number of solutions are proposed to counter the inherent drawbacks of this design, and it is felt that the advantages outweigh the disadvantages.

Carbon↗
PubMed1995

Needs of occupational exposure sampling strategies for compliance and epidemiology.

Although a great deal of occupational exposure data is collected, it is probably insufficient to truly answer the question of legislative compliance, ill directed in terms of real workplace risks, and is of little subsequent use for epidemiological research. This paper is an attempt to summarise the more important components and requirements of a sampling strategy, and it is therefore aimed at those with this responsibility. Perhaps, all too frequently, the more esoteric nature of these issues and their research means that they are published in journals outside the normal sphere of readership, or when it is within that sphere the quantity of statistical nomenclature and content makes it too daunting to attempt to read. By simplifying and summarising, this paper is intended to help justify a change in the sampling programme and to initiate debate.

Data Collection↗
PubMed1995

Exposure to polycyclic aromatic hydrocarbons in coal liquefaction workers: impact of a workwear policy on excretion of urinary 1-hydroxypyrene.

OBJECTIVE: This study was undertaken to assess whether contaminated personal clothing worn beneath a coverall (normal workwear) is a source of potentially significant dermal exposure to polycyclic aromatic hydrocarbons (PAHs) in coal liquefaction workers. METHODS: An intervention study was conducted over a two week period involving 10 workers that reflected the range of activities performed at the factory. A cross over design was used to examine the influence of normal workwear (personal clothing worn beneath a coverall) and intervention workwear (new coverall, shirt, trousers, underwear, socks, and boots) upon excretion of urinary 1-hydroxypyrene (1-OHP) and skin pad deposition of pyrene. RESULTS: The impact of intervention was noted in three ways: (1) A notable reduction (55%) in the mass of 1-OHP excreted on the first day of the intervention phase was found. The median reduction in mass excreted (22.7 nmol) was significant from zero at the 5% level; (95% confidence interval (95% CI) 9.5-40.8 nmol). (2) A notable reduction (82%) in skin pad deposition of pyrene on the first day of the intervention phase was found. The median reduction of 13.20 ng.cm-2 was significant from zero at the 5% level; (95% CI 7.3-26.4 ng.cm-2). (3) About a 50% reduction in 1-OHP concentration over the working week occurred during the intervention phase; an increase of 2.07 mumol/mol creatinine was found from the start to the end of the work period during the intervention phase compared with an increase of 4.06 mumol/mol creatinine during the normal phase. This reduction was not significant at the 5% level. CONCLUSION: The results indicate that on the first day of the working week investigated, significant reductions in absorbtion (as measured by excretion of urinary 1-OHP) and deposition of PAHs (as measured by skin pad deposition of pyrene) can be effected by improvements in workwear policy. The impact of the improved workwear regimen was also detected by reduction in spot urinary 1-OHP concentrations, although this effect was less pronounced. One implication of the findings is that exposure to PAHs may arise from workers' own contaminated personal clothing. As a consequence of this study an improved workwear policy has been implemented at the factory.

Adult↗
PubMed1994

Colophony--uses, health effects, airborne measurement and analysis.

Colophony (rosin) is a widespread natural product obtained form species of the pine family Pinaceae. One of the most important uses of unmodified rosin is in electronic solder fluxes while the main areas of use of chemically modified rosin are paper sizing, adhesives, paints, varnishes, printing inks and plasticisers. Colophony is well recognized as a skin sensitizer and is also the third highest cause of occupational asthma. However, the specific allergens involved particularly in occupational asthma have not been comprehensively assessed or identified. This paper reviews method of colophony production, its uses and health effects and discusses the important issue of its chemical analysis and the choice of a suitable marker for monitoring colphony fume.

Air Pollutants, Occupational↗
PubMed1994

The effects of incorporation of bromodeoxyuridine into mammalian DNA on the migration patterns of DNA fragments subjected to pulsed-field gel electrophoresis after X irradiation or cutting with a restriction enzyme.

Incorporation of bromodeoxyuridine (BrdU) into DNA in both Chinese hamster ovary (CHO) cells and human melanoma (U1) cells reduced the rate of DNA migration in transverse alternating-field electrophoresis (TAFE) agarose gel optimized for separating molecules larger than 2 Mb. This "BrdU migration effect" was independent of the method of damaging the DNA; i.e., the effect was observed after irradiation of the cells or treatment of the plugs containing DNA with the restriction enzyme, Mlu-1, and similar results were found for CHO and U1 cells. However, when the amount of cutting of DNA was estimated from the amount of DNA migrating from the plugs, a difference between U1 cells and CHO cells was observed in that incorporation of BrdU enhanced the cutting of DNA by either irradiation or Mlu-1 digestion for U1 cells but not for CHO cells. Therefore, the "BrdU migration effect" could not be attributed to an increase in large molecules because of reduced cutting of the BrdU-labeled DNA. The decrease in migration rate during pulsed-field gel electrophoresis when BrdU replaces thymidine in the DNA is hypothesized to result from the increase in negative charge on BrdU-labeled DNA. An increase in electron charge density is expected to increase the reorientation time of BrdU-labeled DNA fragments during each voltage pulse due to an increase in the elongation length of the DNA caused by an increase in electronegativity.

Animals↗
PubMed1993

A new member of the cytokine receptor gene family maps on chromosome 21 at less than 35 kb from IFNAR.

A full-length cDNA corresponding to a gene mapping to the D21S58 locus was cloned. The encoded protein, called CRF2-4, was shown to be a typical class II member of the cytokine receptor family. The gene encoding CRF2-4 spans more than 30 kb. Its intron/exon structure was determined and shown to be conserved with all other members of the cytokine receptor family. The physical distance between the CRF2-4 gene and its IFNAR neighbor has been narrowed to less than 35 kb.

Amino Acid Sequence↗
PubMed1993

Respiratory health effects of carbon black: a survey of European carbon black workers.

A study population of 3086 employees was identified in 18 carbon black production plants in seven European countries. Respiratory health questionnaires, spirometry, and chest radiographs were used to estimate effects on health and personal monitoring procedures were employed to measure current exposure to inspirable and respirable dust along with sulphur and carbon monoxide. The low concentrations of gaseous contaminants made the generation of their current and cumulative exposure indices impossible. Low responses from some plants restricted the final analysis to 1742 employees in 15 plants (81% response rate) for respiratory symptoms and spirometry, and 1096 chest radiographs from 10 plants (74% response rate). In total, 1298 respirable and 1317 inspirable dust samples, as well as 1301 sulphur dioxide and 1322 carbon monoxide samples were collected. This study is the first to include a comprehensive and concurrent assessment of occupational exposure to carbon black dust and its associated gaseous contaminants. Cough, sputum, and the symptoms of chronic bronchitis were found to be associated with increasing indices of current exposure. Lung function tests also showed small decreases in relation to increasing dust exposure in both smokers and non-smokers. Nearly 25% of the chest radiographs showed small opacities of category 0/1 or greater. These were strongly associated with indices of cumulative dust exposure. The findings are consistent with a non-irritant effect of carbon black dust on the airways combined with dust retention in the lungs. Further cross sectional studies are planned to investigate whether long term exposure to carbon black dust causes damage to the lung parenchyma.

Adolescent↗
PubMed1993

Physical mapping of chromosome 21.

Chromosome 21, the smallest human chromosome, has been the subject of intense study because it is the chromosome which, when present in an extra copy, leads to Down Syndrome. Moreover, there are genes important for several human genetic disorders on this chromosome, and a significant number of individuals with aneuploidies of regions of the chromosome have been identified. A high fidelity, high resolution physical map of chromosome 21 will be of immense value in generating an accurate genotype/phenotype map of the chromosome and in identifying and isolating genes on the chromosome which may be responsible for various human genetic disorders. Here we describe the current status of our attempts to create such a map. This includes attempts to integrate various physical mapping approaches. Progress towards construction of a minimal set of yeast artificial chromosomes (YACs) spanning the chromosome is described.

Chromosome Mapping↗
PubMed1992

Human chromosomal localization of genes encoding the gamma 1 and gamma 2 subunits of the gamma-aminobutyric acid receptor indicates that members of this gene family are often clustered in the genome.

The gamma-aminobutyric acid (GABA) receptors are the major inhibitory neurotransmitter receptors in the brain and the site of action of a number of important pharmacological agents including barbiturates, benzodiazepines, and ethanol. The gamma 1 and gamma 2 subunits have been shown to be important in mediating responses to benzodiazepines, and a splicing variant of the gamma 2 subunit, gamma 2L, has been shown to be necessary for ethanol actions on the receptor, raising the possibility that the gamma 2 gene may be involved in human genetic predisposition to the development of alcoholism. We have assigned the human genes encoding the gamma 1 and gamma 2 subunits of the GABAA receptor to chromosomes 4 and 5, respectively, by PCR amplification of human-specific products from human-hamster somatic cell hybrid DNAs. Using panels of chromosome-specific natural deletion hybrids, we have further localized the gamma 1 gene (GABRG1) to 4p14-q21.1 and the gamma 2 gene (GABRG2) to 5q31.1-q33.2. These data indicate that the gamma 1 gene may be clustered together with the previously mapped alpha 2 and beta 1 genes on chromosome 4 and that the gamma 2 gene may be close to the previously localized alpha 1 gene on chromosome 5. To further examine the latter possibility the alpha 1 gene was mapped using the chromosome 5 deletion hybrids and shown to be within the same region as the gamma 2 gene, 5q31.1-q33.2. A PCR-based screening strategy was used to isolate a 450-kilobase human genomic yeast artificial chromosome clone containing both the alpha 1 and gamma 2 genes. Pulsed-field gel restriction mapping of the yeast artificial chromosome indicates that the two genes are within 200 kilobases of each other. The data presented here provide further evidence for the nonrandom organization of the human genome by demonstrating that members of the GABAA receptor gene family often occur in small gene clusters widely distributed in the genome.

Base Sequence↗
PubMed1992

The structure of the human interferon alpha/beta receptor gene.

Using the cDNA coding for the human interferon alpha/beta receptor (IFNAR), the IFNAR gene has been physically mapped relative to the other loci of the chromosome 21q22.1 region. 32,906 base pairs covering the IFNAR gene have been cloned and sequenced. Primer extension and solution hybridization-ribonuclease protection have been used to determine that the transcription of the gene is initiated in a broad region of 20 base pairs. Some aspects of the polymorphism of the gene, including noncoding sequences, have been analyzed; some are allelic differences in the coding sequence that induce amino acid variations in the resulting protein. The exon structure of the IFNAR gene and of that of the available genes for the receptors of the cytokine/growth hormone/prolactin/interferon receptor family have been compared with the predictions for the secondary structure of those receptors. From this analysis, we postulate a common origin and propose an hypothesis for the divergence from the immunoglobulin superfamily.

Base Sequence↗
PubMed1992

Occupational exposure to carbon monoxide and sulphur dioxide during the manufacture of carbon black.

The manufacture of carbon black is known to generate carbon monoxide and sulphur dioxide in the 'production gas' and the pyrolysis products of the 'production gas', respectively. Adverse health effects have been reported as associated with both contaminants (coronary heart disease with carbon monoxide and respiratory morbidity with sulphur dioxide). A major cross-sectional and longitudinal respiratory morbidity study is being conducted to assess the effects of exposure to carbon black on lung function, on chest X-rays and on responses to a questionnaire. The questionnaire includes questions on respiratory and cardiovascular symptoms, so that information regarding confounding exposure is essential. The working population of 18 manufacturing plants in seven European Countries was split into 13 job title numbers (1-13) which were then amalgamated into five job categories (A-E), with an appropriate (statistically) number of samples taken from each plant-job category. In total, 1322 carbon monoxide samples and 1301 sulphur dioxide samples were taken, using actively pumped longterm colorimetric tubes. In the majority of cases, more than half of the samples in each plant-job category were either zero or trace, thereby preventing the accurate estimation of the average exposure. The highest median carbon monoxide concentration was from the amalgamated data from all 18 plants in job number 9 (furnace operators), the highest median sulphur dioxide concentration was only 'trace'. The large number of zero and trace values also precluded the generation of current and retrospective exposure indices.

Air Pollutants, Occupational↗
PubMed1992

Occupational exposure to carbon black in its manufacture.

Carbon black is manufactured by the vapour phase pyrolysis of heavy aromatic hydrocarbon feedstocks. Its manufacture is worldwide and the majority of its production is for use in the rubber industry especially tyre manufacture. Its carbonaceous nature has led many to investigate the occurrence of exposure-related medical conditions. To quantify any such relationships, it is necessary to assess exposure accurately. As part of such an epidemiological investigation survey involving the measurement both of respirable and of total inhalable carbon black was undertaken in 18 plants in seven European countries between mid-1987 and mid-1989. A total of 1298 respirable samples (SIMPEDS cyclone) and 1317 total inhalable samples (IOM head) were taken and deemed of sufficient quality for inclusion in the study. The distributions of the time-weighted average values were assessed and found to be best described by a log-normal distribution, and so exposure is characterized by geometric means and standard deviations. The data are presented in terms of 13 separate job titles for both dust fractions and shows a wide variation between job titles, with the highest mean exposure experienced by the site cleaners, and 30% of the samples taken from the warehouse packers being in excess of the relevant countries' occupational exposure limits for total inhalable dust. The quality and extent of this data allows both for comparison with exposure standards and for generation of occupational exposure indices, which will be presented in another paper (Gardiner et al., in preparation).

Carbon↗
PubMed1992

The suitability of the urinary metabolite 1-hydroxypyrene as an index of poly nuclear aromatic hydrocarbon bioavailability from workers exposed to carbon black.

Levels of airborne dust have been measured in the breathing zone of five warehouse packers in a carbon black manufacturing plant on consecutive days over 1 week. Post-shift urine samples were collected on individuals over the week and the concentration of the pyrene metabolite 1-hydroxypyrene have been measured. A questionnaire was used to assess the likelihood of potential confounding factors, such as direct exposure to feedstock oil, as well as smoking and diet. The arithmetic mean both of airborne dust and of excreted 1-hydroxypyrene for each individual have been correlated (a) with the constraint that the regression line pass through the origin, and (b) without this constraint. The slope of the regression through the origin was significant and that of the second regression (not through the origin) was not. The statistical test to determine whether excretion on days after Monday was higher than that on Monday itself proved highly significant. The results suggest that 1-hydroxypyrene may be a useful indicator of exposure to the PNAs adsorbed onto carbon black.

Biological Availability↗