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Biomedical subjects

E M Clark

Publications and source records attributed to E M Clark.

At least 19 recordsLinked to original sources
PubMed1990

d(TG)n.d(CA)n sequences upstream of the rat prolactin gene form Z-DNA and inhibit gene transcription.

Two alternating purine-pyrimidine sequences of the d(TG)n.d(CA)n-type (170bp and 60 bp in length) lie upstream of the rat prolactin (rPRL) gene. Conformational studies of plasmids containing these sequences indicate that both form left-handed (Z) DNA, with transitions initiating at superhelical densities of -0.041 and -0.044 respectively. These alternating purine-pyrimidine (APP) sequences are hypersensitive to cleavage with S1 nuclease both at the boundaries and within these APP repeats, where there is a loss in APP alternation. We have investigated the function of one of these Z-DNA sequences in the regulation of rPRL transcription, by linking regions of the 5' flanking sequence of the rPRL gene to a reporter gene encoding chloramphenicol acetyltransferase (CAT), and transferring these plasmids into GH3 pituitary tumour cell lines. The major conclusion from these studies is that the 170bp repeat exerts a negative effect on the transcription of the rPRL gene, and also down-regulates the expression of the fusion gene pRSVcat when cloned 50bp upstream of the Rous sarcoma virus promoter. However, despite its proximity to an estrogen response element in prolactin, this sequence does not affect the responsiveness of the rPRL gene to estrogen.

Animals↗
PubMed1990

The comparability of two commonly used carbon monoxide analysis systems: a technical note.

Carbon monoxide (CO) in expired breath is a common strategy for verifying smoking abstinence. The purpose of this investigation was to determine the comparability of two carbon monoxide (CO) analyzers: the commonly used Ecolyzer Series 2000 analyzer versus the new, highly portable, and less expensive Ecolyzer Model 210. Fifty-eight CO readings were obtained from 29 subjects (17 smokers, 12 nonsmokers) and analyzed on both systems simultaneously. Results indicated that the analyzers yielded highly comparable values for both smokers and nonsmokers. Moreover, the correlation between the two units' readings was very high (r = .92, p less than .001). There was, however, a significant analyzer by sex interaction with the Series 2000 analyzer yielding higher values for males. Overall, it was concluded that the Series 210 analyzer is a highly accurate and cost-effective instrument.

Adolescent↗
PubMed1987

Insulin therapy in patients with poorly controlled non-insulin dependent diabetes mellitus.

In spite of maximal doses of sulphonylurea agents, patients with poorly controlled non-insulin dependent diabetes (NIDDM) often do not have improved metabolic control after the introduction of insulin therapy. We have assessed 22 patients with NIDDM who commenced insulin therapy in order to identify those characteristics which were associated with an improvement in glycaemic control. Twelve months after the commencement of insulin therapy, 14 (64%) patients showed a decrease in glycosylated haemoglobin (HbA1) levels; 12 of the 14 (55%) patients had achieved HbA1 levels that were considered to reflect acceptable glycaemic control (HbA1 less than or equal to 11%; reference range, 6%-9%). The HbA1 levels in the other patients either remained unchanged or had increased (one subject). When the subjects who had achieved good glycaemic control with insulin therapy were compared with the remainder of the group, a failure to improve with insulin therapy was associated with a longer duration of diabetes, greater obesity and higher levels of cholesterol and triglycerides before the commencement of insulin therapy. Greater obesity and high levels of circulating lipids were found by means of multiple linear regression analysis to correlate independently with a poor response to insulin therapy. We conclude that standard insulin therapy can improve the majority of patients with poorly controlled NIDDM. However, there is a substantial number of patients, who tend to be obese and have high levels of circulating lipids, whose condition does not improve with insulin therapy, or who require more aggressive dosage increases than are used as a routine.

Adult↗
PubMed1987

Outpatient initiation of insulin therapy in patients with diabetes mellitus.

Before insulin therapy is begun, patients with diabetes are often admitted to hospital. In a retrospective study we have reviewed the initiation of insulin therapy in 54 unselected outpatients (12 of whom were insulin-dependent), when the initial stabilization of therapy was performed predominantly by nurse educators. Most patients found the procedure satisfactory; only one subject indicated dissatisfaction with the regimen and only two indicated that they would have preferred admission to hospital. No patient experienced an acute hypoglycaemic or hyperglycaemic problem that required admission to hospital nor was emergency intervention required during the 12 months that followed the initial stabilization period of insulin therapy. Metabolic control, as measured by glycosylated haemoglobin levels, improved in the majority of both insulin-dependent and non-insulin-dependent patients after 12 months of insulin therapy. A retrospective cost analysis that compared the cost of the outpatient procedure with the cost (hospital-bed costs only) of initiating insulin therapy in a similar group of patients who were admitted to hospital, indicated a saving of $1857 for each outpatient. We conclude that the outpatient initiation of insulin therapy is feasible where the facilities for education about diabetes exist, that it is safe, achieves satisfactory metabolic control, is acceptable to most patients, and offers a considerable saving in costs.

Australia↗
PubMed1979

The development of resistance to methotrexate in a mouse melanoma cell line. I. Characterisation of the dihydrofolate reductases and chromosomes in sensitive and resistant cells.

PG19T3 mouse melanoma cells were selected for resistance to methotrexate. Nine sub-lines that are resistant to concentrations of methotrexate ranging from 1.27 x 10(-7) M, to 1 x 10(-4) M methotrexate were selected and characterised in terms of their content of dihydrofolate reductase activity and their chromosomes. The intracellular level of dihydrofolate reductase activity increases with increasing resistance such that at the highest level of resistance PG19T3:MTXR10(-4)M cells contain approximately 1,000 fold more enzyme activity than the parental PG19T3 cells. It is shown that the enhanced activity is due to an increase in the amount of the enzyme rather than any structural change to the enzyme in resistant cells. Comparisons of pH activity profiles, profiles under different activating conditions and titrations with methotrexate suggest that the sensitive and resistant cells contain identical dihydrofolate reductases. Analysis of the chromosomes of resistant cells shows the presence of up to 5 large marker chromosomes which contain homogeneously staining regions after G-banding. These same regions stain intensely after C-banding and fluoresce brightly after staining with Hoechst 33258. The size of homogeneously staining regions increases throughout the process of selection. For one marker chromosome this increase may have been mediated via a ring chromosome.

Animals↗
PubMed1979

Respiratory morbidity and exercise-induced bronchoconstriction in children.

A sample of 99 children had lung function tests before and after exercise. Sixteen had a decrease in lung function after exercise (forced expiratory flow) of more than 20 per cent, which indicated an important degree of exerciseinduced bronchospasm. Review of the medical records for the total sample revealed that those with exercise-induced bronchospasm had a higher consultation rate for respiratory symptoms, while their consultation rate for non-respiratory symptoms was the same as the remainder of the sample. These findings suggest that bronchial lability may be a predisposing factor in some respiratory diseases.

Bronchial Spasm↗
PubMed1976

Cholinomimetic teratogens. IV. Effects of the genotype for muscular dystrophy in chickens.

Embryos of a family of chickens homozygous for muscular dystrophy (md/md) reacted with a higher incidence of malformations to treatment with carbachol than did White Leghorn embryos. The same difference in response of embryos from the two stocks occurred after treatment with sulfanilamide. Embryos of reciprocal crosses between these two stocks differed greatly, however, in their response to carbachol, F1 embryos from dystrophic hens producing a much higher incidence of malformations than did those from Leghorn hens. In contrast, both F1 sibs reacted similarly to sulfanilamide, the teratogenic effects being intermediate between those of embryos from the parent stocks.

Abnormalities, Drug-Induced↗