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Biomedical subjects

A Johnstone

Publications and source records attributed to A Johnstone.

9 recordsLinked to original sources

Changes in mRNA levels of poly(ADP-ribose) polymerase during activation of human lymphocytes.

The level of mRNA encoding the nuclear enzyme poly(ADP-ribose) polymerase (ADP-ribosyltransferase, EC 2.4.2.30) was found to be very low in quiescent human lymphocytes and to increase at least 10-fold between 1 and 2 dyas after stimulation with the mitogen phytohaemagglutinin, staying high for several days thereafter. This increase was inhibited by 3-methoxybenzamide (a competitive inhibitor of poly(ADP-ribose) polymerase) but was not affected significantly by aphidicolin. Incubation of activated cells with cycloheximide for 2 h increased the expression slightly. These data demonstrate that, during lymphocyte activation, the level of mRNA of the poly(ADP-ribose) polymerase gene correlates with, and hence is presumably responsible for, the increase in poly(ADP-ribose) polymerase protein detectable by enzyme assay or immunochemistry.

Aphidicolin

Phosphoinositide hydrolysis in mitogen-stimulated human peripheral-blood T lymphocytes.

Both phytohaemagglutinin and antibodies to the CD3 molecule induced proliferation and phosphoinositide hydrolysis in human peripheral-blood T lymphocytes, but the magnitude of the inositol phosphate response was small and the rate of accumulation slow [significant increases in Ins(1,4,5)P3 were observed only after 10 min]. Hence this response differs from the well-characterized Ins(1,4,5)P3 responses of many other systems. This slow response, its abrogation in Ca2+-depleted medium, the slow and maintained increase in Ca2+ as measured by Quin-2, and the ability of the Ca2+ ionophore A23187 to stimulate Ins(1,4,5)P3 accumulation all suggest that the increase in Ins(1,4,5)P3 occurs, at least in part, as a result of receptor-mediated Ca2+ influx in mitogen-stimulated T lymphocytes.

Antibodies, Monoclonal

Differential control of proto-oncogene c-myc and c-fos expression in lymphocytes and fibroblasts.

In lymphocytes stimulated with the mitogen phytohaemagglutinin, an inhibitor of the enzyme ADP-ribosyltransferase (ADPRT) completely blocks the proliferative response and the increase in expression of the proto-oncogene c-myc without affecting c-fos significantly. Conversely, in fibroblasts the serum-induced growth is not affected by the ADPRT inhibitor, and both oncogenes are dramatically super-induced. Hence there are differences between lymphocyte and fibroblast early responses to mitogenic stimulation and also between regulation of c-fos and c-myc gene expression.

Benzamides

The outcome of hidden neurotic illness treated in general practice.

One thousand patients attending a general practice surgery were asked to complete the general health questionnaire as the first stage of screening for hidden minor psychiatric disorders. Those who had an unexpectedly high score of 20 or more were randomly allocated to doctors or health visitors for treatment. After one year, these two groups were reinterviewed by the doctors and health visitors respectively and comparable rates of recovery were found. After five years, they were interviewed again and a second general health questionnaire completed. It was found that both groups had improved significantly, and that there was no significant difference between them.Poor outcome was associated with problems with children, household or neighbours and with a previous history of psychiatric illness. Improvement was associated with physical treatment of the original disorder, resolution of the original problem and job satisfaction.The implication of these findings for the comparative management of minor psychiatric disorders by general practitioners and non-medical health workers in primary care are discussed.

Allied Health Personnel

The evaluation of a model speech training program for deaf children.

Systematic speech training procedures were employed with a group of 20 hearing-impaired children ranging in age from 7 to 10 years. Using a primarily auditory-oral approach, the speech training program employed a hierarchical sequence in order to teach the suprasegmental patterns of English to the children. The children's performance on the speech training hierarchy was monitored on a daily basis using a checklist system. Based on their rate of progress in the development of speech skills, the children were divided into three groups post hoc: rapid, slow but steady, inordinately slow. Although the system worked well, on the average, approximately one-third of the children encountered serious difficulites at one or more levels of the hierarchy. Examination of the children's background information and audiological data revealed that those children who encountered difficulty had an extremely limited amount of residual hearing and/or problems other than a hearing handicap.

Child

Dominant lethal assays in male mice: evaluation of experimental design, statistical methods and the sensitivity of Charles River (CD1) mice.

Male CD1 mice were dosed by intraperitoneal injection of 20, 40 or 80 mg of methyl methanesulphonate (MMS) per kg body weight or with the solvent, water. After dosing, each male was caged with (a) 2 or (b) 3 females per week for 8 consecutive weeks and 13 days after mating the females were killed and examined for evidence of dominant lethal mutations. Results were analysed to determine (1) the sensitivity of CD1 mice to the mutagenic effect of MMS. (2) the influence of the number of females mated with each male. (3) the adequacy of the experimental design and (4) the adequacy of the statistical methods. A dose-related increase in early foetal deaths was induced in females mated to male mice in the first week after dosing with 20, 40 and 80 mg/kg MMS. A reduction in foetal implants was demonstrated in females in the 40 and 80 mg/kg MMS groups but not after dosing males with 20 mg/kg. Thus dominant lethal mutations were induced in male CD1 mice dosed IP with 20, 40 and 80 mg/kg giving a degree of sensitivity which compares favourably with that obtained with other strains of mice in other laboratories. For a given number of male mice, the greater precision obtained with 3 rather than 2 females arose directly from the numbers used. For a given number of female mice, the allocation of 2 per male (rather than 3 per male) is a more efficient design in that 50% more treated animals are available for estimation of the relevant error. Also more information would be available as a result of the probable increase in pregnancy rate. The experiment did not suggest the need for any modification in the statistical approach.

Animals

Psychiatric screening in general practice. A controlled trial.

This study reports the efficacy of the General Health Questionnaire (G.H.Q.) in the secondary prevention of minor psychiatric illness in a primary-care setting. 1093 consecutive attenders at a general practitioner's surgery were screened for minor psychiatric disorder using the G.H.Q. 32% were found to have a conspicuous psychiatric disorder and a further 11% had a hidden psychiatric disorder. The group with hidden disorders were randomly assigned to a treated index group and an untreated control group. The effects of case detection and treatment were beneficial and immediate, with the duration of episode of the disorder being much shorter for patients whose disorder was recognised by the general practitioner. For patients with more severe disorders there are significant differences still demonstrable between the groups one year later; but patients with mild disorders do equally well, some recovering spontaneously but others becoming manifest to the general practitioner over the next year and so receiving treatment. The "detected" group of patients increased their consultations for emotional complaints over the next year, but their total consultation-rate was not increased.

Clinical Trials as Topic

Changes in topoisomerase I activity after irradiation of lymphoid cells.

The activity of topoisomerase I in nuclear extracts increased about three-fold 5 min after gamma-irradiation (840-2500 rads) of human peripheral blood lymphocytes or cultured lymphoblastoid cells. The change may reflect modification of the enzyme by nuclear ADP-ribosyl transferase, which is known to be activated by DNA breaks.

Cell Line