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Biomedical subjects

M J Gardner

Publications and source records attributed to M J Gardner.

At least 19 recordsLinked to original sources
PubMed1992

Homologies between the contiguous and fragmented rRNAs of the two Plasmodium falciparum extrachromosomal DNAs are limited to core sequences.

Plasmodium falciparum contains two extrachromosomal DNAs, a 6 kb linear element and a 35 kb circular DNA; both encode rDNA sequences. The 6 kb element rDNAs comprise fragments of both large and small subunit rRNAs. Comparison of these with corresponding rDNA sequences from the 35 kb DNA and E. coli show that sequences conserved between the three are largely confined to highly conserved core regions; in fact, most of the 6 kb rDNA sequences correspond to core regions. Both the 6 kb element and 35 kb rDNAs show less conservation to each other than to E. coli sequences, suggesting that the two extrachromosomal DNAs of P. falciparum are not closely related. The characteristics of the fragmented rRNAs from the 6 kb element suggest they are functional, possibly in mitochondrial ribosomes.

Animals↗
PubMed1992

Subcellular fractionation of the two organelle DNAs of malaria parasites.

Malaria parasites contain two extrachromosomal DNAs, a 6 kb repetitive linear molecule which is assigned on the basis of its genetic content to the mitochondria, and a 35 kb transcriptionally active circular molecule whose intracellular location is not known. We used the polymerase chain reaction to detect and estimate the numbers of both molecules in sub-cellular fractions derived from the rodent parasite Plasmodium yoelii. The two DNA molecules were not coordinately partitioned by the fractionation process, the 6 kb molecule being more abundant, relative to the 35 kb circle, in a fraction enriched for mitochondria, the converse being true for a less dense fraction of unknown identity. This implies that the two molecules are located in different cellular compartments, and is consistent with other evidence suggesting they have different evolutionary origins.

Animals↗
PubMed1992

Discrimination between myocardial infarct and ventricular tachycardia patients using magnetocardiographic trajectory plots and iso-integral maps.

Magnetocardiograms were recorded from 30 normal (N) subjects, 15 myocardial infarct (MI) patients, and 15 ventricular tachycardia (VT) patients. Discrimination between the groups was affected by iso-integral magnetic field mapping (MFM) and trajectory plotting of MFM extrema. Iso-integral MFM for the QRST, QRS, and ST-T intervals was created for each test group member. A polarity score, based on the number of extrema features present, was assigned to each iso-integral MFM. Differences in group mean integral of QRST map polarity scores were significant (p less than 0.05) between MI and N, between VT and N (p less than 0.005), and between MI and VT (p less than 0.05) subjects. integral of ST-T map polarity scores were significantly (p less than 0.0001) different between VT and N and between MI and VT (p less than 0.001) subjects. Discrimination between MI and VT patients, based on polarity score difference, was 56% accurate using integral of QRS maps and 73% accurate using integral of ST-T maps. For each subject, time-normalized MFM was used to construct trajectory plots of the maxima and minima in the QRS and ST-T intervals. Discrimination between MI and VT patients was based upon intergroup differences in fragmented trajectory plots. When the number of discrete trajectories and/or the total number (F) of trajectory points at which discrete trajectories coexist were considered, QRSmin trajectory plots were significantly (p less than 0.05) different for VT and N, but not for MI and N subjects. The significant (p less than 0.05) difference between MI and VT trajectory plots enabled 76% accuracy for MI and VT identification. ST-Tmax trajectory plots show significantly (p less than 0.0001) higher F values for VT patients facilitating accurate (87%) discrimination between MI and VT patients. These results suggest that the abnormalities of repolarization processes, displayed by MFM as multipolar integral of ST-T maps and/or as fragmented trajectory plots of ST-T extrema, may be useful indicators of the arrhythmia substrate/processes that characterize VT and vulnerable MI patients.

Diagnosis, Differential↗
PubMed1992

Lung cancer mortality among workers in the European production of man-made mineral fibers--a Poisson regression analysis.

One hundred and eighty-one lung cancer deaths among workers during 301,085 person-years in European man-made mineral fiber production between 1930-1955 and 1982 were analyzed according to Poisson regression models including age, calendar period, country, and exposure variables. Time since first employment was the variable most strongly associated with lung cancer risk in both the rock-slag wool and glass wool subcohorts. Workers in the early technological phase were at higher risk than those in other categories, particularly in rock-slag wool production. No clear trend with duration of employment was suggested. No major changes occurred in the interpretation of the results when workers with less than one year of employment or less than 20 years since first exposure were excluded. The original results, based on analyses for standardized mortality ratios, were confirmed, and workers with a short duration of employment or a short time since first employment did not need to be excluded from the analysis.

Air Pollutants, Occupational↗
PubMed1992

Leukemia in children and paternal radiation exposure at the Sellafield nuclear site.

Childhood cancer around nuclear installations has been studied in recent years, particularly in the United Kingdom but also in other countries. The early studies were prompted by the suggestion of a 10-fold raised level of childhood leukemia around the Sellafield nuclear site in England, which was confirmed and followed by the identification of generally smaller excesses around some (but not all) other nuclear sites in the United Kingdom. Marked excesses have not been reported in other countries. The increased leukemia rate around Sellafield has been further investigated by examining individual cases in detail in epidemiological cohort and case-control studies. The raised incidence seems to have been concentrated in children born in the local area but not among children who moved in after birth and was particularly associated with fathers who had experienced higher levels of occupational external ionizing radiation exposure at Sellafield before their children's conception. The underlying cause of this statistical association is not yet clear, but the findings have important potential implications for radiobiology and for protection of radiation workers and their children.

Adult↗
PubMed1991

Approaches to investigating clusters: by example, childhood leukaemia near Sellafield.

There is occasionally concern about suspected clusters of disease in geographically localised areas among members of the general public or other groups. These occurrences need a systematic approach to their investigation. Such an approach needs to consider the definition and characteristics of the cluster and of the putative environmental cause for concern. Depending on the outcome of these considerations there will be different actions, possibly involving epidemiological studies. The necessary components of the approach and resulting actions are outlined in this paper, and illustrated by the example of childhood leukaemia rates around the Sellafield nuclear plant.

Case-Control Studies↗
PubMed1991

Organisation and expression of small subunit ribosomal RNA genes encoded by a 35-kilobase circular DNA in Plasmodium falciparum.

A restriction map of the 35-kb circular DNA molecule of Plasmodium falciparum showed that a region of about 6 kb, encoding both a large and a small subunit ribosomal RNA gene, has been duplicated in inverted orientation. The complete sequence of one small subunit rRNA gene is presented as well as an analysis of transcripts from erythrocytic stage parasites. Comparative sequence analysis of the rRNA gene and the proposed secondary structure of the rRNA suggest that it is of organellar origin. Intriguingly, while some characteristics of the small subunit rRNA gene are similar to mitochondrial sequences, others are more like those of plastids. The origin of the circular DNA molecule and evolutionary implications of its genetic content are discussed.

Animals↗
PubMed1991

8th Duncan Memorial Lecture. Childhood cancer and nuclear installations.

So where are we now? I think the first thing to say is that there is a well-established excess around Sellafield of childhood leukaemia, although excesses around other nuclear sites are of a lower magnitude. The excess near Sellafield is strongly associated with fathers having high exposure to external whole-body penetrating radiation while working at the installation before their child's conception. But is this association pointing towards a causal mechanism? One possibility is genetic damage, but most geneticists and radiobiologists would consider that the levels of occupational exposure, even at Sellafield, are too low for this to be a plausible pathway on current knowledge. This is based to some extent on the lack of any similar effect among children born subsequently to Japanese survivors of the atomic bombs--however, the scenario is somewhat different contrasting a high short-term exposure with a lower long-term exposure. As well, some workers at Sellafield will also be exposed to radionuclides, such as plutonium, which we have not yet been able to analyse for. In addition, there are other exposures in a complex environment which may or may not be relevant. One experimental study in the laboratory using animals supports the idea that a pathway through irradiation of the parents is plausible, although this one result needs replication. Other causes have been suggested for the excess childhood leukaemia levels in particular around nuclear establishments--these include population movement, implicating viruses that have long been considered to be associated with childhood leukaemia, high rates in isolated communities, and also selection of areas for nuclear sites that have a natural propensity to high rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effects of increasing heart rate induced by efferent sympathetic neuronal stimulation, isoproterenol or cardiac pacing on myocardial function and oxygen utilization.

The effects of increasing heart rate by six different methods on cardiac function were investigated in 17 open-chest anesthetized dogs. Heart rate was increased approximately 30% by (1) right interganglionic nerve stimulation, (2) atrial pacing, (3) ventricular pacing, (4) atrioventricular sequential pacing, (5) right stellate ganglion stimulation, and (6) isoproterenol administration. During heart rate increases induced by atrial pacing left ventricular intramyocardial pressure, coronary blood flow, oxygen delivery per unit of myocardial oxygen consumption, and myocardial efficiency were unchanged. Ventricular pacing reduced left ventricular cavity and septal intramyocardial pressure, while circumflex coronary flow increased, resulting in reduced oxygen delivery relative to myocardial oxygen consumption. Similarly, atrioventricular sequential pacing increased circumflex coronary artery flow and myocardial oxygen consumption, and decreased septal intramyocardial pressure and oxygen delivery per unit of myocardial oxygen consumption. Right stellate ganglion stimulation and isoproterenol increased left anterior descending and circumflex coronary artery blood flow, intramyocardial pressure, and myocardial oxygen consumption. Estimated myocardial efficiency (left ventricle) was decreased by ventricular pacing and isoproterenol, and was unchanged by atrial pacing and right interganglionic nerve stimulation. Increases in heart rate induced by right interganglionic nerve stimulation did not alter myocardial oxygen consumption, or the index of cardiac efficiency. It is concluded that augmentation of heart rate by either ventricular or atrioventricular pacing impairs myocardial function so that there is a decrease of left ventricular efficiency and isoproterenol augments chronotropism and myocardial force relative to cardiac external work so there is a reduction in cardiac efficiency. In contrast, atrial pacing or right interganglionic nerve stimulation augments chronotropism such that myocardial oxygen consumption and efficiency are unchanged.

Animals↗
PubMed1979

Prevalence of gall stones at necropsy in nine British towns: a collaborative study.

A prospective study of the prevalence of gall stones at necropsy in nine towns in England and Wales showed considerable geographical variations. The age- and sex-standardised prevalence ranged from 20.6% in Ipswich to 9.2% in Wakefield. The distribution of gall stones differed from that of all-cause mortality and was negatively correlated with that of mortality from ischaemic heart disease. Socioeconomic influences related to affluence do not appear to be major determinants of the distribution of gall stones.

Adult↗