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Biomedical subjects

J D Buckley

Publications and source records attributed to J D Buckley.

10 recordsLinked to original sources
PubMed1992

The aetiology of cancer in the very young.

Epidemiological studies of cancer in young children have implicated a number of environmental factors, which need to be studied in more detail, but it is probably fair to say that the main benefit of these studies has come from the negative findings, which have served to exclude (or at least place an upper limit on the role of) potential risk factors. Our inability to identify environmental causes could mean either that the environment does not substantially affect cancer incidence in young children, or that we are simply not looking in the right places. Most attention has naturally been focused on the known and suspected environmental carcinogens and mutagens. Based on the data summarised in this paper, one possibility is that the most important mutagen is endogenous: 5-methyl-cytosine. If so, factors increasing cancer risk could be those which increase the rate of spontaneous deamination, or impair the efficiency of the excision repair enzymes, or regulate the processes of CpG methylation and demethylation. These factors could still be classed as mutagens in their own right, since they would lead to an increase in uncorrected point mutations, but they would be distinctive in a number of ways. Firstly, since the role of methylation in bacteria is very different from that in eukaryotic cells the Ames mutagenicity assay could not be relied upon to detect methylation-mediated mutagens. Furthermore the risk may be highly age dependent, reflecting changes in methylation patterns with growth and cellular differentiation. Agents which disrupted the imprinting process in the testis would not be detectable by animal carcinogenicity tests unless specifically looked for.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1979

Pretreatment with acetylaminofluorene enhances the repair of O6-methylguanine in DNA.

Epidemiological and experimental evidence suggests that the interplay of environmental factors may be particularly relevant to the induction of cancer in man. We have investigated the possible interrelationships, at the level of DNA repair, of two chemically different hepatocarcinogens administered to rats. Animals were pretreated for several weeks by inclusion of 2-acetylaminofluorene (AAF) in the diet and a study was made of the capacity of liver to repair lesions subsequently introduced into DNA by a pulse of dimethylnitrosamine (DMN). Of particular interest was the repair of adducts at the O6 position of guanine as this product has been implicated as a critical reaction site for carcinogenesis by the monofunctional alkylating agents. We show here that the capacity of liver to repair O6-methylguanine in DNA is enhanced by prolonged exposure of rats to the chemically unrelated agent, AAF.

2-Acetylaminofluorene↗
PubMed1979

Pregnancy in chronic active hepatitis.

The outcome of pregnancy in chronic active hepatitis (CAH) was studied retrospectively, together with a survival analysis of patients and a comparison of fertility with that expected from controls drawn from the normal Australian population. Clinical records of 73 cases of CAH included 37 women who were potentially fertile (aged 15-45 years) and there were 30 pregnancies among 16 of these women. Hepatic and obstetric complications and the outcome for the foetus and the mother were compared with the results from 36 reports accumulated from the literature. The results showed an incremental increase in survival of patients with CAH according to decade of diagnosis from 1950 and similar severity of liver disease in those who did, or did not, become pregnant. Fertility was reduced in patients with CAH. Relapse of CAH occurred during pregnancy in only two patients, hepatic complications were minimal, and there was no consistent pattern of alteration in liver function; 12 of 16 mothers are alive for a mean period of eight years after pregnancy. Obstetric complications included urinary tract infections (six), toxaemia of pregnancy (nine) and prematurity (seven); of the 30 pregnancies, four were terminated on medical advice in the early years of the study, three ended in spontaneous abortion, and there were four perinatal deaths giving a foetal loss rate of 33 per cent. Despite the maternal disease and use of prednisolone and azathioprine during pregnancy, the single congenital abnormality was pyloric stenosis. We conclude that in CAH fertility is reduced but pregnancies which occur can proceed without detriment to the mother provided that prednisolone treatment is maintained; that a higher than normal foetal loss can be expected; and that babies may be born prematurely but will be normal.

Abortion, Spontaneous↗
PubMed1978

Social factors and clinical disease: a checklist data base for correlative analysis.

The adequate care of a patient entails consideration of his social and psychological problems in addition to the relevant medical data. To facilitate this integrated approach, a Social Work Indices Checklist (SWIC) is described, and its use in practice is illustrated. A narrative report is generated from a possible 3095 items of information recorded in SWIC.

Attitude↗
PubMed1978

A 'profile' of immune responsiveness in multiple sclerosis.

An 'immunological profile' of various indices of B-cell function and T-cell function was developed for the 'early' case of multiple sclerosis (MS). This was compared against two groups of controls comprising age and sex-matched healthy subjects, and patients with other disabling neurological diseases (CNS controls) who were matched for age, sex, and type and duration of disability. Some indices of humoral immune responsiveness, such as the induced primary response to monomeric flagellin and the 'resting' levels of antibody to measles and rubella viruses, showed significant augmentation. Cellular immune deficits were attributed to an illness effect per se because (a) cell-mediated immunity was depressed, but only when compared with that of healthy subjects and not when compared with that of the CNS controls, and (b) transformation responses of lymphocytes to viral antigens were inversely related to disability status. The abnormalities in humoral immune responses demonstrable in this study do not provide an explanation for this disease; if there is a relevant 'immunological fault', the nature of this needs to be sought from within the neuraxis rather than from the systemic circulation.

Adult↗
PubMed1978

Factors influencing the secondary antibody response to flagellin in man.

The secondary antibody response to 5.0 microgram flagellin was studied by haemagglutination in 132 healthy or convalescent subjects given a primary challenge with 5.0 microgram flagellin from 1 to 44 months previously. The peak titre, expressed as total antibody, occurred at 2 weeks and was mainly immunoglobulin (Ig)G. The magnitude of the titre of total antibody was influenced predominantly by that of total antibody in the primary response (P less than 0.001), the interval between primary and secondary responses (P less than 0.005) and the subjects' age (P less than 0.05) and sex (P less than 0.08). Together these accounted for 23% of the variability observed in the secondary response, with total antibody titre in the primary response accounting for 11% of the variability. The titre of IgG antibody was likewise influenced by these four variables, but the influence of age or sex on IgG antibody was not statistically significant. In human vaccination programmes, choice of the appropriate interval between primary and booster inoculations could increase prophylactic effectiveness and, if two inoculations were to prove as effective as three, there would be reduced work and increased public acceptance. Moreover, the demonstrable capacity for responsiveness of aged and debilitated persons should encourage the wider use of appropriate prophylactic immunization in these groups.

Adolescent↗
PubMed1977

Use of a computer-based postal questionnaire for the detection of hypothyroidism following radioiodine therapy for thyrotoxicosis.

A computer-processed postal questionnaire was devised to detect hypothyroidism in patients treated previously for thyrotoxicosis with radioiodine. In a study of 232 patients treated with 131I at the Royal Melbourne Hospital between four and ten years previously, the sum of symptomatic answers in the questionnaire was a sensitive discriminator of hypothyroidism, and allowed 80% of euthyroid patients to be excluded from further assessment. Questions concerned with general well-being and energy, voice and skin changes, showed the highest sensitivity and specificity. The combination of these questions alone was an effective means of identifying hypothyroidism, with a sensitivity and specificity comparable to the more sophisticated technique of discriminant function analysis. Hypothyroidism had an incidence of between 20% and 35% six to eight years after 131I therapy and was related to a smaller initial goitre size for a given dose of 131I. This postal questionnaire, in conjunction with a computer-based automatic recall system, promises to be an efficient and reliable screening tool for the detection of hypothyroidism in the increasing number of patients "at risk" following 131I therapy.

Australia↗
PubMed1975

Thyrogastric autoimmune disease. Studies on the cell-mediated immune system and histocompatibility antigens.

Cell-mediated immune responses were studied in autoimmune diseases of thyrogastric type, Hashimoto's thyroiditis and autoimmune pernicious anaemia-type gastritis. Specific cell-mediated immunity was investigated by the leucocyte migration inhibition procedure, and general cell-mediated immunity (T-cell performance) was studied by standard in vivo and in vitro tests. In thyrogastric autoimmune diseases inhibition of migration of leucocytes was induced by thyroglobulin and gastric parietal cell microsomes; under conditions of presumably low cellular sensitization, stimulation of migration was observed. There was no depression of general cell-mediated immunity, in contrast to what occurs in systemic lupus erythematosus and related autoimmune diseases. A weak association of autoimmune gastritis with HL-A3 and HL-A7 (P LESS THAN 0.05) lost significance when an appropriate correction was applied; this weakness with HL-A clearly does not explain the strong genetic component in thyroid and gastric autoimmunity.

Anemia, Pernicious↗