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J S Marway

Publications and source records attributed to J S Marway.

At least 19 recordsLinked to original sources
PubMed1996

Application of proton NMR spectroscopy to measurement of whole-body RNA degradation rates: effects of surgical stress in human patients.

The urinary catabolites, N2,N2-dimethylguanosine (DMG), pseudouridine (PSU) and 7-methylguanine (m7-Gua) are formed from post-transcriptional methylation of RNA bases and are not reincorporated into RNA upon its degradation. Their quantitative urinary excretion may be used to determine rates of whole body degradation of individual RNA species since DMG occurs exclusively in tRNA, PSU occurs in rRNA and tRNA and m7-Gua occurs in all RNA species. Conventional HPLC analysis has several drawbacks since pre-analytical steps may involve selective losses and, under certain conditions, other urinary analytes may co-elute. In the present paper, we report analysis of these compounds by high-field 1H-nuclear magnetic resonance (1H-NMR) spectroscopy. Urinary concentrations of these metabolites were found to be in agreement with previously published HPLC and ELISA determinations. However, NMR analysis required minimal sample preparation (other than lyophilisation and reconstitution) and was capable of the simultaneous determination of other relevant analytes such as creatinine. This technique was therefore applied to urine samples from patients who had undergone surgical stress and insulin-like growth factor-1 (IGF-I) therapy. Surgical stress increased the excretion of DMG and m7-Gua. Degradation rates for tRNA and mRNA were also higher in surgically stressed subjects when compared with controls but degradation rates of rRNA decreased by approx. 30%. However, injection of IGF-I (40 micrograms/kg s.c.) had no significant effect on the excretion of these nucleosides. These data indicated that IGF-I therapy has no marked effects on RNA turnover following trauma. We suggest that this technique can be applied to study of RNA metabolism in any surgical or medical condition. Furthermore, since only 0.6 ml of urine is required, studies in neonates seem to be feasible.

Adult↗
PubMed1996

Osmotic diarrhoea and skeletal muscle protein synthesis in vivo.

The pathogenic nature of the wasting seen in diarrhoea is unknown. This study measured protein synthesis in an established model of diarrhoea using lactose for seven days. Comparisons were also made with data obtained from rats fed an identical diet in which lactose was replaced by isocaloric glucose ad libitum (that is, the control diet). To account for diarrhoea induced anorexia, a third group of rats were included, which were fed identical amounts of the control diet as the rats with diarrhoea inducing diet. Comparisons of the diarrhoea induced group with rats fed the control diet ad libitum showed that diarrhoea caused a significant reduction in body weights. Type I and type II muscles showed significant reductions in protein, RNA, and DNA contents, as well as a fall in the derived parameters, RNA/DNA, protein/DNA, and RNA/protein. Fractional rates of protein synthesis (ks) were also reduced. However, synthesis rates of type I and II muscles relative to RNA (kRNA) were unchanged in these muscles in diarrhoea induced rats compared with ad libitum fed controls. In the jejunum there was an increase in the RNA/DNA ratio, and reductions in ks and kRNA. Comparisons were also made between rats with diarrhoea and rats pair fed the control diet. There were no changes in total muscle protein, RNA or DNA contents. This suggests that an important feature of body wasting in diarrhoea is the element of anorexia, which induces severe metabolic changes. The comparison between rats with diarrhoea and the pair fed group showed that histological features of the plantaris were not overtly changed, though diarrhoea caused significant reductions in RNA/DNA, protein/DNA, ks, and kRNA. Similar changes were seen for the soleus; though the reduction in ks failed to attain statistical significance. In the jejunum a comparison of diarrhoea induced rats with pair fed controls, showed increases in the ratios of RNA/DNA and protein/DNA.

Animals↗
PubMed1995

The acute effects of ethanol and acetaldehyde on the synthesis of mixed and contractile proteins of the jejunum.

An investigation was made into the acute effects of ethanol and acetaldehyde with or without enzyme inhibitors of alcohol dehydrogenase (4-methylpyrazole) and aldehyde dehydrogenase (cyanamide) on fractional rates of protein synthesis of mixed and contractile proteins of the jejunum. Ethanol decreased the fractional rates of mixed and contractile protein synthesis (i.e. ks, defined as the percentage of tissue protein renewed each day) by approximately 25%. Pretreatment with 4-methylpyrazole followed by treatment with ethanol further reduced mixed and contractile ks by approximately 30%, when compared with saline plus saline and 4-methylpyrazole plus saline groups. The greatest reductions in ks of mixed and contractile proteins occurred with cyanamide pretreatment followed by ethanol treatment; mixed and contractile protein ks in the cyanamide plus ethanol group decreased by approximately 60% when compared with saline plus saline and cyanamide plus saline groups, whereas ks decreased by approximately 45% when compared with the saline plus ethanol injected group. Acetaldehyde treatment alone caused no significant inhibition of protein synthesis. However, 4-methylpyrazole pretreatment plus acetaldehyde treatment significantly reduced mixed and contractile ks by approximately 20% when compared with the saline group, and by approximately 15% when compared with the 4-methylpyrazole plus saline and saline plus acetaldehyde groups. These data show that ethanol alone and perhaps high levels of acetaldehyde may be responsible for the inhibition of intestinal protein synthesis and related pathological derangements, e.g. motility disturbances due to loss of contractile proteins.

Acetaldehyde↗