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Biomedical subjects

D C Lloyd

Publications and source records attributed to D C Lloyd.

At least 73 records · Page 4Linked to original sources

Chromosomal radiosensitivity of lymphocytes from Alzheimer's disease patients.

We have examined chromosome aberrations in gamma irradiated (3 Gy) lymphocytes from five patients with Alzheimer's disease (AD). In each case, the number of dicentrics was significantly higher than the number in irradiated lymphocytes from five age matched normal subjects, the mean value for AD cells being about 25% higher. There was no significant difference in number of acentrics between AD and normal cells. Examination of the number of first, second, and third division metaphases, using fluorescence plus Giemsa staining, indicated that there was no difference in cycling time between AD and normal cells, and that after irradiation both groups showed the same mitotic delay. The similarity of our findings to those of others with irradiated Down's syndrome cells (from adult patients) is discussed.

Aged↗

Sister-chromatid exchanges induced by mitomycin C after acute or chronic exposure of human lymphocytes to a low dose of X-rays.

Human peripheral blood lymphocytes from 10 male donors were exposed to mitomycin C with and without prior irradiation with 0.01 Gy X-rays. Acute or chronic irradiation of lymphocytes in G1 resulted in a decrease in the subsequent level of mitomycin C-induced sister-chromatid exchange aberrations. The effect was small (approximately 10%) with evidence of some variability between donors. By contrast no adaptive response was observed if the cells were treated in G0.

Adaptation, Physiological↗

Radiation induction of micronuclei in human lymphocytes.

An examination of the cytokinesis-blocked micronucleus technique confirmed its potential usefulness as a method of biological dosimetry for radiation accidents. Several advantages and disadvantages of the system are discussed. It has been demonstrated that under the conditions of these experiments, the blocking agent, cytochalasin B does not induce micronuclei or unstable chromosome aberrations. The induction of sister-chromatid exchanges proved just significant. Analysis of the dose response for 250 kVp X-rays indicates that although the Y = alpha D + beta D2 model fits the data, the relationship does not correspond to that for total aberration induction as might have been expected. The background frequency of micronuclei and the value of the alpha coefficient are higher than for total aberrations and the beta term is lower. This indicates that simple incorporation of acentric chromosome fragments into micronuclei may not wholly account for the phenomenon.

Adult↗

Frequencies of chromosomal aberrations induced in human blood lymphocytes by low doses of X-rays.

The dose-response for radiation-induced chromosome aberrations in human lymphocytes is usually fitted to the quadratic model. This assumes that the slope is essentially linear at low doses. Empirical observations of linearity at less than 200 mGy are, however, sparse. Some data have been published indicating a non-linear (threshold) response and these are reviewed. In particular one study with X-rays showed a plateau in response up to 50 mGy and with a significant dip below the control level at 4 mGy. The mechanism proposed to explain non-linearity is that low doses stimulate the enzymic repair capability of lymphocytes. Preliminary data are presented from a large experiment by six laboratories in which the low dose-response for X-rays has been re-examined. The plateau in the dose-response relationship, if it exists, does not extend to doses above approximately 10 mGy. No irradiated cells yielded aberration levels significantly below the control. Over the range 0-300 mGy the response can be fitted to a linear regression. There are, however, variations in sensitivity between cells from different donors. An unexpected finding was that some lymphocytes contained greater than 1 exchange aberrations. This may indicate a small subset of cells that are especially susceptible to the induction of aberrations by low doses.

Adult↗

In vitro induction of chromosomal aberrations in human lymphocytes, with and without boron 10, by radiations concerned in boron neutron capture therapy.

A beam consisting of mainly 24 keV neutrons has been constructed for radiobiological studies to evaluate the potential of these particles for treating deep tumours by the boron capture reaction. The induction of chromosomal aberrations in human lymphocytes in vitro was examined and a linear dose effect with a relative biological effectiveness similar to fission neutrons was obtained. For samples placed at depths in a plastic phantom the aberration yields declined with depth at a rate matching the fall in the sum of dose due to proton recoils and neutron capture in nitrogen 14. The presence of boron 10 at 30 micrograms ml-1 did not affect the aberration yield. By using the mixed sample method, the probability of interphase death or mitotic delay in cells crossed by an alpha particle or lithium-7 ion produced in the boron capture reaction was shown to be close to 1.0. Thus these cells are prevented from coming to mitosis in culture. The implications for boron capture therapy are that this filtered beam has a "high LET" effect which could lead to poor normal tissue sparing. However there may be a significant therapeutic advantage due to a high probability of killing tumour cells that have incorporated boron 10.

Boron↗

A collaborative exercise on cytogenetic dosimetry for simulated whole and partial body accidental irradiation.

An experiment sponsored by the International Atomic Energy Agency was undertaken to compare dose estimation by cytogenetic analysis on aliquots of samples of irradiated blood sent by air to participating laboratories. Accidental acute whole-body irradiations to 0.7 and 2.34 Gy and half-body irradiations to 3.5 Gy were simulated with X- and gamma-rays. For the partial irradiations the size of the irradiated fraction and its dose were estimated by the Qdr and contaminated Poisson techniques. Each laboratory's in vitro dose-response data were fitted to the quadratic model by the iteratively reweighted least squares method. Interlaboratory variations in dose-response curves, and in the aberration yields and dose estimates for the simulated accidents were noted. However, in general, most participants consistently obtained results acceptably close to the true values.

Accidents↗

An assessment of the metaphase finding capability of the Cytoscan 110.

The Cytoscan 110 metaphase finder has been tested with cultures of human peripheral blood lymphocytes prior to its introduction into routine use for the analysis of radiation-induced chromosomal damage. Cells of varying quality and density of distribution on slides, stained with orcein or Giemsa, were examined by the same technician using the Cytoscan and a conventional microscope. The Cytoscan was able to locate rapidly (less than 2 min) virtually all metaphases known to be present and with an acceptably low rate of false positives. The presence of mixtures of FPG-stained first- and second-division spreads did not reduce its efficiency in metaphase finding. The instrument automatically divides the objects that it locates into 4 quality ranks and this was very effective in separating good metaphases, suitable for high-magnification scoring, from unscorable spreads and debris. With cultures of X-irradiated blood it was shown that the criteria by which the Cytoscan locates metaphases and ranks their appearance do not introduce bias in the yields of dicentric and other unstable chromosome-type aberrations.

Automation↗

Chromosomal damage induced in human lymphocytes by low doses of D-T neutrons.

Unstable chromosome aberrations induced by in vitro irradiation with zero plus seven low doses of 14.8 MeV D-T neutrons in the range 3.55-244 mGy have been analysed in human peripheral blood lymphocytes. In order to obtain the required large numbers of scored cells for such low doses, fourteen laboratories participated in the experiment. The dose responses for dicentrics, excess acentrics and total aberrations, fitted well to the Y = alpha D model. The alpha coefficient of yield for dicentrics, 1.60 +/- 0.07 X 10(-2) Gy-1, compares well with the values obtained in previous studies with D-T neutrons at somewhat higher doses. Results from a previous collaborative study using 250 kVp X-rays over a comparable dose range indicated the possible existence of a threshold below 50 mGy. In the present study there is no clear evidence for neutrons for such a threshold. However, the data were insufficient to permit the rejection of a possible threshold below approximately 10 mGy.

Chromosome Aberrations↗

Chromosome aberrations induced in human lymphocytes by 8.7 MeV protons and 23.5 MeV helium-3 ions.

This paper describes the irradiation of thin samples of blood with 8.7 MeV protons and 23.5 MeV helium-3 ions in the track segment mode. Chromosome aberrations in human lymphocytes have been scored. The relationship between dicentric yield and dose in Gy was Y = 0.044 D + 0.058 D2 for protons and Y = 0.394 D for helium ions. These results are compared with data from other laboratories using protons and an attempt is made to reconcile differences. An unexpected observation was that the ratio of the linear coefficients for helium ions and protons was about 9 whereas the ratio of the l.e.t. values was 4.5. This disagrees with current theory which predicts that the linear coefficients should be proportional to l.e.t. Possible sources of error in our experiments are discussed but do not adequately account for the discrepancies.

Chromosome Aberrations↗

The influence of parity, age and maturity of pregnancy on antimicrobial proteins in human milk.

Sequential samples of colostrum, transitional and mature milk from 47 women were investigated to determine the concentrations of 11S IgA, IgG, IgM, alpha 1-antitrypsin, lactoferrin, lysozyme, B1A globulin (C3) and B1E globulin (C4) by single radial immunodiffusion. These were all found to be high in colostrum with a decline in concentration as lactation proceeds although a wide variation in concentration was noted between different individuals at any given post-partum time interval. For each time interval considered, parity, age and maturity of pregnancy did not appear to influence significantly the variation in protein concentrations. Statistical analyses of the results obtained from samples taken during the first four days of lactation, when protein concentrations were highest, showed that parity and age did influence the variation in antimicrobial protein concentrations when examined using an analysis of variance but significantly higher concentrations of protective proteins were not consistently seen in the milk from any one or more parity or age groups. Mean concentrations of all proteins excluding IgA were found to be greater in those women delivering before their expected date of confinement during the first four days of lactation. This was statistically significant for C3 and C4 and approaching significance (p less than 0.08) for alpha 1-antitrypsin.

Adolescent↗

Sequential changes in the antimicrobial protein concentrations in human milk during lactation and its relevance to banked human milk.

The concentrations of eight antimicrobial proteins, 11S IgA, IgG, IgM, alpha 1-antitrypsin, lactoferrin, lysozyme, C3, and C4 were measured in sequential samples of colostrum, transitional and mature milk from 47 women in Merseyside, England by single radial immunodiffusion. Concentrations were highest in colostrum and then declined until relatively stable concentrations were reached in mature milk. A wide variation in protein concentrations was noted in the milk from different individuals at any given postpartum time interval and this was particularly so during the first 4 days postpartum. The decline in individual antimicrobial protein concentrations seen in samples of transitional milk appeared to take a variable period of time to stabilize to mature milk concentrations of each protein. These variations may reflect different rates of transport or secretion of these proteins from the alveolar epithelial cells into the alveolar lumen. Because of the wide variations in antimicrobial proteins observed in milk samples from the individuals in this study at similar postpartum time intervals, it is suggested that banked milk should be monitored not only for bacterial contamination, but also for levels of antimicrobial proteins, if it is considered that a major advantage of unprocessed human milk is the immune protection which it confers.

Complement C3↗

The clastogenic effect of irradiated human plasma.

Normal unirradiated human lymphocytes were cultured in medium containing 20 per cent homologous or autologous plasma collected from samples of blood exposed in vitro to various doses of X-irradiation. Metaphases were stained by the BrdU/FPG method. The yields of chromatid-type aberrations in cells at first mitosis (M1 cells) were similar for cultures containing plasma irradiated at 0, 0.05 or 0.25 Gy but were significantly increased at 0.5, 5.0 and 10.0 Gy. The response was dose dependent but the data were insufficient to propose a particular model of dose response. The absence of chromosome-type aberrations confirmed the suggestion that earlier workers' observations of dicentrics and rings were artefacts of long culture times. The level of chromosomal damage was unaffected by omitting folic acid from the medium. Irradiated plasma did not alter the frequency of sister chromatid exchange observed in M2 cells. The ratios of M1, M2 and M3 cells were markedly affected by the presence of irradiated plasma which caused a dose-dependent speeding up of the cell cycle.

Adult↗

The dose response relationship obtained at constant irradiation times for the induction of chromosome aberrations in human lymphocytes by cobalt-60 gamma rays.

The induction of unstable chromosome aberrations in human peripheral blood lymphocytes exposed in vitro to protracted doses of cobalt-60 radiation is presented. Four dose response curves have been produced using constant exposure times of 1,3,6, and 12 h. The data fit well to the linear quadratic model and the yield coefficients have been compared with those obtained for acute (less than 10 min) exposure. The quadratic coefficient is dependent on irradiation time and decreases approximately as predicted by Lea and Catcheside's G-function hypothesis. The possibility of a small proportion of much longer lived breaks is discussed. For purposes of biological dosimetry it is sufficient to assume a mean time of 2 h and a single exponential function for the repair of lesions when relating the effects of brief and protracted exposure.

Chromosome Aberrations↗