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Biomedical subjects

R Mace

Publications and source records attributed to R Mace.

13 recordsLinked to original sources
PubMed1996

Role of postreplicative DNA mismatch repair in the cytotoxic action of thioguanine.

It is proposed here that the delayed cytotoxicity of thioguanine involves the postreplicative DNA mismatch repair system. After incorporation into DNA, the thioguanine is chemically methylated by S-adenosylmethionine to form S6-methylthioguanine. During DNA replication, the S6-methylthioguanine directs incorporation of either thymine or cytosine into the growing DNA strand, and the resultant S6-methylthioguanine-thymine pairs are recognized by the postreplicative mismatch repair system. Azathioprine, an immunosuppressant used in organ transplantation, is partly converted to thioguanine. Because the carcinogenicity of N-nitrosamines depends on formation of O6-alkylguanine in DNA, the formation of the analog S6-methylthioguanine during azathioprine treatment may partly explain the high incidence of cancer after transplantation.

Animals↗
PubMed1989

Nicotine regulation among heavy and light smokers in a non-stressful environment.

The purpose of this study was to assess nicotine regulation among "heavy" and "light" smokers. Previous studies supporting the nicotine regulation model of smoking behavior have suggested that smokers compensate for a reduction in the amount of nicotine available in their cigarette by altering smoking frequency, puff volume, or other aspects of smoking topography. However, little is known about a smoker's decision to smoke a specific cigarette, and the concurrent changes in their blood nicotine. Manipulation of nicotine levels in the blood could play a critical role in smoking maintenance, by regulating the extent and quality of the CNS effects of smoking. In this study, 24 heavy and light smokers (cotinine above or below 260 ng/ml) smoked high- (1.0 mg) or low- (0.5 mg) dose nicotine cigarettes while watching non-stressful movies. Blood nicotine was assessed before and after smoking a preload and free operant cigarette. The results showed that blood nicotine levels after smoking the free operant cigarette were significantly more consistent (lower standard error) for the heavy smokers, following a low dose, as opposed to a high-dose preload. Light smokers showed a non-significant trend towards being more consistent when the high-dose nicotine preload was used. This suggests that heavy smokers may have maximized their dose of nicotine whenever available nicotine was in relatively short supply (low dose condition). However, light smokers may have minimized their exposure when available nicotine was relatively more plentiful (high dose condition).

Adult↗
PubMed1989

The effects of smoking on the mood, cardiovascular and adrenergic reactivity of heavy and light smokers in a non-stressful environment.

Following a period of overnight deprivation, 58 smokers participated in a 90-min laboratory assessment in which they viewed a non-stressful movie and smoked two 0.5-mg nicotine-containing cigarettes. The first cigarette was given to all subjects following 25 min of adaptation and baseline. The next cigarette was provided at their request, which occurred 9-12 min later. "Heavy" and "light" smokers were grouped according to their average morning cotinine values, which fell above or below 250 ng/ml, respectively. The results showed that, relative to their baseline, heavy and light smokers experienced about the same level of post-smoking change in blood nicotine, heart rate and blood pressure. However, heavy smokers showed a significantly greater delta from baseline in post-smoking measures of epinephrine, norepinephrine, tension reduction and increase in vigor enhancement. A strong and consistent correlation was observed between post-smoking increases in epinephrine, tension reduction and increased vigor.

Adult↗
PubMed1987

International Commission for Protection against Environmental Mutagens and Carcinogens. ICPEMC Working Paper No. 15/6. Effect of ethanol on nitrosamine metabolism and distribution. Implications for the role of nitrosamines in human cancer and for the influence of alcohol consumption on cancer incidence.

Alcohol consumption is associated with an increase in the incidence of cancers of several sites, including oesophagus, larynx and mouth. The mechanism of the induction of cancer by alcohol is not clear. Humans are exposed to a variety of carcinogenic N-nitroso compounds. Ethanol changes the pharmacokinetics of nitrosamines in rats particularly by decreasing the ability of the liver to metabolize them. A hypothesis is put forward that the influence of alcohol on human cancer is mediated by its effect on the metabolism and distribution of nitrosamines from the diet, from tobacco smoke and from endogenous synthesis.

Alcohol Drinking↗
PubMed1986

Stress inoculation training to control anxiety in sport: two case studies in squash.

This study arose as a result of two squash players, one male one female, seeking advice on how to improve their mental approach to playing. They both felt that their game suffered badly through too much anxiety. After preliminary interviews it was decided to use a programme of stress inoculation training to help them learn to control their anxiety. In order to obtain baseline measures of anxiety, both subjects completed a state anxiety questionnaire on five occasions, immediately prior to playing important league or team matches. They were then given eight training sessions. On completion of the training, subjects were asked to complete a further five state anxiety tests immediately prior to analogous matches. There was a considerable decrease in self-reported anxiety levels and both players reported that their performance had improved. It is argued that stress inoculation training is potentially very useful as a technique for controlling anxiety in certain competitive sports.

Adaptation, Psychological↗
PubMed1986

Stress inoculation training: a case study in gymnastics.

A young female gymnast of regional squad potential had ceased to make progress when she resumed training after a series of injuries and was given stress inoculation training to help her to regain her form. Preliminary interviews revealed that she had developed a number of negative self-statements and images which, it was hypothesised, may have been contributing towards her lack of progress. In order to replace these with positive self-statements and images a treatment programme of eight training sessions was implemented. Recorded interviews and subsequent comparison of comments made by the subject before and after the intervention programme, indicated that the training had been successful. This was endorsed by the coaches who reported an improved attitude to training and rapid progress in skill learning.

Child↗
PubMed1984

Ethanol and dimethylnitrosamine and diethylnitrosamine metabolism and disposition in the rat. Possible relevance to the influence of ethanol on human cancer incidence.

Alcohol consumption is associated with an increase in human cancer, notably of the oesophagus. We have found that ethanol will alter profoundly the distribution of two carcinogenic nitrosamines in the rat. Small oral doses of dimethylnitrosamine (NDMA) are absorbed from the portal blood as it passes through the liver, and do not reach the extrahepatic organs. Ethanol, equivalent to a man drinking 1 pint (0.5 l) of beer, prevents this first pass clearance in the rat and exposes sensitive extrahepatic organs to this carcinogen. As a consequence the alkylation of kidney DNA by 35 micrograms NDMA/kg body weight was increased 4.6-fold by concurrent administration of 240 mg ethanol/kg, and smaller doses of [14C]-NDMA produced detectable alkylation of kidney DNA only if the rats were given ethanol. Measurement of metabolism of NDMA by liver slices confirmed that this action of ethanol is the result of inhibition by ethanol of NDMA metabolism in liver (Ki = 0.5 mM). Comparison of urinary excretion in man and rat suggests that ethanol also inhibits first pass clearance of NDMA in man. There was no complete first pass clearance of diethylnitrosamine (NDEA), but while ethylation of kidney DNA was decreased by ethanol, that of oesophageal DNA was increased between 1.8- and 4.6-fold. Measurement of the metabolism of NDEA to CO2 by liver slices, kidney slices, and oesophageal epithelium suggest that the changes in alkylation of kidney and oesophageal DNA are the result of selective inhibition of NDEA metabolism in liver and kidney. The ethylation of oesophageal DNA was greater relative to liver after a small dose than after a large dose possibly because of the low Km of the oesophageal metabolic activating system relative to that in liver and kidney. These results explain experiments showing that concurrent administration of ethanol increases the carcinogenicity and alters the organs affected by these nitrosamines. It is tentatively proposed that the effect of ethanol on human cancer incidence is mediated through similar influences on the metabolism and disposition of the nitrosamines to which man is exposed.

Alkylation↗
PubMed1983

Deuterium isotope effect on metabolism of N-nitrosodimethylamine in vivo in rat.

The maximal rates of metabolic oxidation of N-nitrosodimethylamine (NDMA) and N-nitrosodimethylamine-d6 (NDMA-d6) in vivo (VH and VD, respectively) have been measured by following 14CO2 exhalation in rats after intraperitoneal injection of the two 14C-labelled carcinogens at high doses (20 or 40 mg/kg). Complete deuteration of NDMA reduced only slightly the maximal rate of metabolism when the two substrates were administered separately (VH/VD approximately 1.2). However, much larger (approximately 4-fold) deuterium isotope effects were observed when mixtures of NDMA with NDMA-d6 were injected. These results are tentatively interpreted as evidence that C-H bond cleavage is not a rate limiting feature of overall metabolism, but that the complex between NDMA and the principal enzyme(s) metabolizing it in vivo freely equilibrates with unbound substrate. Single, large, intraperitoneal doses of NDMA and NDMA-d6 produced a similar alkylation of rat liver DNA and also of kidney DNA. However, a small oral dose (54 micrograms/kg) of NDMA-d6 produced 1/3 less alkylation of liver DNA and 3 times as much alkylation of kidney DNA as did an equimolar dose of NDMA. The reduction in alkylation of liver DNA correlates well with, and possibly explains, the decreased ability of NDMA-d6 to induce liver tumors in rats. The associated increase in the alkylation of kidney DNA suggests that this change is due to a decrease in the amount of nitrosamine removed from the portal blood on the first pass through the liver.

Animals↗
PubMed1980

Induction of kidney tumours by a single dose of dimethylnitrosamine: dose response and influence of diet and benzo(a)pyrene pretreatment.

Seven days on a protein-free diet increases the susceptibility of rats to the action of DMN as a renal carcinogen. The dose response for the induction of kidney tumours by a single dose of dimethylnitrosamine (DMN) in these rats is reported. The first tumour was not found until 28 weeks after the dose. At 100 weeks the incidence ranged from 22.5% at the lowest dose (20 mg/kg) to 97% at the highest dose (60 mg/kg). The incidence in probits at any time between 50 and 100 weeks was linearly related to the log dose. Epithelial and mesenchymal tumours were produced in an approximate ratio of 2:1. The protein-free diet alters the rate of metabolism of DMN in the rat, and increases the alkylation of nucleic acids by this carcinogen in the kidney. Further treatment of the rat with benzo(a)pyrene can reverse, to some extent, the change in metabolism, but does not reverse the change in alkylation. It is shown that the change in kidney-tumour incidence produced by the change in diet, and by the treatment with benzo(a)pyrene, corresponds to the changes these treatments produce in the alkylation of kidney DNA by the carcinogen.

Animals↗
PubMedDate not supplied

An evaluation of a multicomponent treatment program involving scheduled smoking and relapse prevention procedures: initial findings.

In the current study, 34 smokers were treated in a smoking cessation program that involved either a scheduled smoking procedure, or a minimal contact self-help treatment control. The interval smoking program consisted of baseline, cessation, and relapse prevention phases. During baseline, subjects self-monitored smoking and the total hours spent awake. During a 3-week cessation period, the scheduled smoking group progressively increased their intercigarette interval, thereby gradually reducing their total daily intake of nicotine. Smokers were expected to quit on a target date set at the end of this period. Cognitive behavioral interventions and relapse prevention training consisted of behavioral rehearsal of nonsmoking skills in a relapse prone environment. Control subjects were given the American Cancer Society "I Quit Kit", and provided subsequent discussion of its use. The results showed that 53% and 41% of the scheduled smoking group was abstinent at the 6- and 12-month follow-up points, respectively. Controls averaged only 6% for the same periods. Scheduled smoking may be a useful addition to a multicomponent treatment program and further study appears warranted to determine the saliency of the treatment features.

Adult↗