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M S Walker

Publications and source records attributed to M S Walker.

12 recordsLinked to original sources

In vivo binding of N-2-acetylaminofluorene and its N-hydroxy derivative to the DNA of fractionated rat liver chromatin.

The in vivo binding of radioactive N-2-acetylaminofluorene (AAF) and N-hydroxy-2-acetylaminofluorene (N-OH-AAF) to the DNA of rat liver chromatin was examined. The chromatin was fractionated into putative transcriptionally active and inactive fractions by hydrodynamic shearing and subsequent glycerol gradient centrifugation, DNAase II digestion followed by MgCl2 aggregation of transcriptionally inactive chromatin, or mild digestion with micrococcal nuclease. Carcinogens were administered for various times prior to sacrifice. Irrespective of the duration of exposure, no preferential binding of either carcinogen to DNA was detected in any of the fractions prepared by hydrodynamic shearing of DNAase II digestion. When micrococcal nuclease was utilized, a 2-fold increase in carcinogen bound to the DNA of that chromatin fraction containing the smallest molecular weight fragments was detected. These small molecular weight fragments produced by micrococcal nuclease have been postulated to be derived from in vivo transcriptional units. Additionally, when DNAase II was used to probe chromatin from rat livers which had been exposed to a carcinogenic regimen of AAF, no preferential binding of radioactive N-OH-AAF to the DNA of any chromatin fraction was detected.

2-Acetylaminofluorene

Screening for Cushing's syndrome using early morning urine samples.

Urinary free 11-hydroxycorticosteroid/creatinine ratios (UFC/Cr)were determined in early morning urine samples from 138 obese subjects attending endocrine clinics in the Glasgow area. The majority of patients (128) had UFC/Cr ratios within the normal range for non-obese subjects (5-55 mumol/mol). Of those with elevated UFC/Cr ratios, further investigations of the hypothalamic-pituitary-adrenal axis confirmed a diagnosis of Cushing's syndrome due to bilateral adrenal hyperplasia in six of the cases and adrenal tumours in a further two patients. In the remaining two patients there was evidence of intermittent adrenal hyperactivity with inconsistent responses to insulin-induced hypoglycaemia tests.

11-Hydroxycorticosteroids

Biosynthesis of 5-(4'5'-dihydroxypentyl) uracil as a nucleoside triphosphate in bacteriophage SP15-infected Bacillus subtilis.

The nucleoside triphosphate of 5-(4',5'-dihydroxypentyl)uracil (DHPU) was detected in the acid-soluble extract from bacteriophage SP15-infected Bacillus subtilis W23. No uracil was found in the DNA of either replicating or mature phage. Labeled thymidine added during phage DNA synthesis was incorporated into phage DNA. The presence of DHPU as a nucleoside triphosphate in the acid-soluble pool and the incorporation of thymidine into phage DNA suggest that both DHPU and thymine are incorporated into SP15 DNA via their nucleoside triphosphates. 5-Fluorodeoxyuridine inhibited biosynthesis of SP15 DNA, and this inhibition was reversed by thymidine, resulting in the synthesis of a DNA containing reduced amounts of fully modified DHPU. It is proposed that 5-fluorodeoxyuridine, or its metabolic product, inhibits a step in the biosynthetic pathway to the nucleoside triphosphate of DHPU.

Bacillus subtilis

Incorporation of label from ribose into 5-(4',5'-dihydroxypentyl) uracil of bacteriophage SP15 DNA.

Radioactively labeled ribose was incorporated into the glucosylated deoxynucleoside monophosphate of 5-(4',5'-dihydroxypentyl)uracil of bacteriophage SP15 DNA to a greater extent than into the other pyrimidine deoxynucleoside monophosphates. Results from formic acid hydrolysis of the deoxynucleoside monophosphates to their bases suggest that label from ribose is incorporated into the dihydroxypentyl side chain of 5-(4',5'-dihydroxypentyl)uracil.

Bacillus subtilis

Excretory patterns of urinary free 11-hydroxycorticosteroids and total oestrogens throughout the normal menstrual cycle.

The excretion of urinary free 11-hydroxycorticosteroids and total oestrogens was studied daily in morning urine specimens throughout the menstrual cycle of six normal women (age range 18-24 years). The follicular phase of the cycle was characterised by apparently random fluctuations in the excretion of urinary free corticosteroids. However, after the mid-cycle oestrogen peak there occurred a significant drop in corticosteroid excretion, which then rose to a peak eight to 10 days after ovulation and was synchronous with the second oestrogen peak during the luteal phase.

11-Hydroxycorticosteroids

Comparative studies of pulsatile and nonpulsatile flow during cardiopulmonary bypass. II. The effects on adrenal secretion of cortisol.

Previous studies have indicated that a significant reduction in plasma cortisol levels occurs during nonpulsatile cardiopulmonary bypass as a result of adrenocorticol hypofunction. The Stöckert pulsatile pump system described in Part I has been employed in a comparative study of plasma cortisol levels in 20 patients subjected to pulsatile or nonpulsatile perfusion during open-heart surgery. The plasma cortisol response pattern in the nonpulsatile group was identical to the pattern previously described, with no significant rise in cortisol levels during the period of perfusion. In the pulsatile group, however, plasma cortisol levels rose significantly during perfusion, reaching a mean level at the end of perfusion which was highly significantly greater than that in the nonpulsatile group (p less than 0.001). Correction of the plasma cortisol values for the effect of hemodilution was performed and, again, corrected cortisol values indicated a highly significant increase in end-bypass levels in the pulsatile groups (p less than 0.001). These results clearly indicate that the reduction in cortisol secretion during nonpulsatile bypass may be prevented by the use of pulsatile perfusion.

Adrenal Glands

Urinary free 11-hydroxycorticosteroid/creatinine ratios in early morning urine samples as an index of adrenal function.

Urinary free 11-hydroxycorticosteroid/creatinine ratios were determined in early morning urine samples from 113 females (age range 20-45 years) and 65 males (age range 22-45 years). Basal values in normal subjects fluctuated between 5 and 55 mumol/mol creatinine. In four patients in whom Cushing's syndrome was diagnosed, urinary free 11-hydroxycorticosteroid/creatinine ratios were greater than 85 mumol/mol creatinine. Administration of dexamethasone (0.5 mg/q.i.d.) to nine normal laboratory staff for two days resulted in a suppression of the urinary free 11-hydroxycorticosteroid/creatinine ratio to less than 50% of the mean basal value in all cases. This degree of suppression did not occur in two cases of Cushing's syndrome due to adrenal tumours.

11-Hydroxycorticosteroids